Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-026-04991-w
Type 2 diabetes (T2D) and its complications represent a complex disorder involving multiple pathophysiological processes. Although conventional therapeutic approaches partially regulate blood glucose, they fail to fundamentally reverse disease progression or effectively prevent complications. This review summarizes the current research advance and challenges of using different forms of mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) in treating T2D and complications. It begins with an introduction to the characteristics of MSC-EVs. Subsequently, the mechanisms and therapeutic prospects of natural MSC-EVs are analyzed, with a focus on their roles in inflammatory modulation, tissue regeneration, and improving insulin resistance. Engineering MSC-EVs, covering strategies including optimizing MSC culture conditions, modifying EV contents, and establishing MSC-EV delivery systems based on bioactive materials are then discussed, which boost EV yield and quality while enhancing therapeutic efficacy. Current challenges, including the limited yield and high heterogeneity of natural MSC-EVs, as well as issues related to long-term safety, immunocompatibility, and large-scale production of engineered MSC-EVs are finally overviewed, with emphasizing artificial intelligence in guiding future research directions. These summaries are crucial for clinical translation of MSC-EVs and will ultimately provide T2D patients with an effective and safe treatment option.
Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-026-04913-w
Background Extracorporeal cardiac shock wave (ECSW) therapy enhances the function of endothelial colony-forming cells (ECFCs), but whether it can serve as a preconditioning strategy to enhance myocardial infarction (MI) therapy remains unclear. This study investigated the efficacy and mechanism of intravenously delivered ECSW-preconditioned ECFCs (SW-ECFCs) in a rat MI model. Methods ECFCs were isolated from the bone marrow of ApoE-/- rats and fully characterized. RNA sequencing of control ECFCs versus SW-ECFCs revealed significant enrichment of the PI3K/AKT pathway. We therefore performed a series of in vitro functional assays on these cells, including Transwell migration, Matrigel tube formation, CCK-8 proliferation, flow cytometric apoptosis analysis, and VEGF-A ELISA. The role of the PI3K/AKT pathway was interrogated using the inhibitor LY294002. Subsequently, an acute MI model was established in ApoE-/- rats via left anterior descending coronary artery ligation. Rats were randomized into four groups: MI+PBS, MI+ECFCs, MI+SW-ECFCs, and MI+LY294002-pretreated SW-ECFCs (LY-SW-ECFCs), with sham-operated rats as controls. Comprehensive evaluations included echocardiography, serum injury biomarkers, TTC, and histopathological (H&E, Masson) staining, immunohistochemical detection of cardiomyocyte apoptosis and p-eNOS, immunofluorescence assessment of ECFC homing and vascular markers (CD31, α-SMA, VEGF-A), tissue/plasma nitric oxide measurement, and Western blot analysis of PI3K/AKT signaling proteins. Results Transcriptomic analysis revealed significant enrichment of the PI3K/AKT pathway in SW-ECFCs. Functionally, ECSW enhanced ECFCs migration, tube formation, proliferation, and VEGF-A secretion, while reducing apoptosis;
Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-026-05044-y
Tooth loss remains a major unmet clinical challenge, and current prosthetic approaches cannot restore the biological complexity, sensory function, or regenerative capacity of natural teeth. Recent progress in stem cell biology, developmental engineering, and regenerative biomaterials has opened new possibilities for biological tooth regeneration. This review integrates advances across three major research domains that together define the current landscape of translational regenerative dentistry. First, we discuss stem cell-based, scaffold-guided strategies for tooth regeneration. These approaches combine dental and nondental stem cells, including DPSCs, SCAPs, PDLSCs, SHED, and iPSC-derived lineages, with bioactive materials such as HA/TCP ceramics, dentin-derived extracellular matrix scaffolds, and natural or synthetic polymers to promote odontogenic differentiation, vascularization, and periodontal attachment. Second, we summarize emerging tooth organoid and bioengineered tooth germ technologies that recapitulate epithelial–mesenchymal interactions and enable controlled reconstruction of dentin–pulp and periodontal compartments for modeling human odontogenesis. Third, we highlight molecular regulation-driven therapeutic strategies, focusing on the modulation of Wnt, BMP, FGF, TGF-β, and USAG-1 pathways to stimulate endogenous tooth regeneration and correct developmental defects. Despite marked progress, challenges remain, including stable neurovascular integration, optimization of stem cell–material crosstalk, precise control of spatiotemporal signaling, and long-term functional stability in vivo. Finally, we outline future directions involving smart biomaterials, gene- and protein-based molecular targeting, organoid-guided regeneration, and iPSC-enabled personalized therapies, which may further accelerate the clinical translation of stem cell-based tooth regeneration.
Stem Cell Research & Therapy•2025•DOI: 10.1186/s13287-025-04148-1
Background The long-term effects and outcomes of human mesenchymal stem cell (MSC) therapy in patients with severe coronavirus disease 2019 (COVID-19) remain poorly understood. This study aimed to evaluate the extended safety and efficacy of MSC treatment in severe patients with COVID-19 who participated in our earlier randomized, double-blind, placebo-controlled clinical trial, with follow-up conducted over 3 years. Methods One hundred patients with severe COVID-19 were randomized to receive either an MSC infusion (n=65, 4×10^7 cells/dose, on days 0, 3, and 6) or a placebo, with both groups receiving the standard of care. At 36 months post-MSC therapy, patients were followed up to long-term safety and efficacy, particularly the effects of MSC therapy on persistent COVID-19 symptoms. Evaluated outcomes included lung imaging results, 6-min walking distance (6-MWD), pulmonary function test results, quality of life scores based on the Short Form-36 (SF-36) health survey, Long COVID symptoms, new-onset comorbidities, tumor marker levels, and rates of COVID-19 reinfection. Results Three years post-treatment, 46.94% (23/49) of patients in the MSC group and 34.48% (10/29) in the placebo group showed normal findings on computed tomography (CT) images (odds ratio [OR]=1.68, 95% confidence interval [CI]: 0.65–4.34). The general health (GH) score from the SF-36 was higher in the MSC group (67.0) compared to the placebo group (50.0), with a difference of 12.86 (95% CI: 1.44–24.28). Both groups showed similar results for total lung severity scores (TSS), 6-MWD, pulmonary function tests, and Long COVID symptoms. No significant differences between groups were observed in new-onset complications (including tumorigenesis) or tumor marker levels. After adjusting for China’s dynamic zero-COVID-19 strategy, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfection rates were 53.06% (26/49) in the MSC group and 67.86% (19/28) in the placebo group (OR=0.54, 95% CI: 0.20–1.41). Conclusions These findings support the long-term safety of MSC therapy in patients with severe COVID-19 over 3 years. MSC treatment may offer potential benefits for lung recovery and improved quality of life in patients experiencing Long COVID symptoms. Trial registration: ClinicalTrials.gov, NCT04288102. Registered 28 February 2020, https://clinicaltrials.gov/study/NCT04288102.
Stem Cell Research & Therapy•2025•DOI: 10.1186/s13287-025-04621-x
Background Mesenchymal stem cells (MSCs) isolated from umbilical cord blood (UCB) exhibit significant therapeutic efficacy in endometriosis; however, the molecular mechanisms governing their regulation remain incompletely elucidated. This study delves into the regulatory functions of miR-210-3p and miR-31-5p, which are secreted via exosomes from hypoxia-damaged endometrial epithelial cells, in modulating the behavior of UCB-MSCs. Methods UCB-MSCs were transfected with specific inhibitors targeting miR-210-3p and miR-31-5p. Proliferation and migratory capacities were quantified using CCK8, EdU incorporation, Transwell, and scratch wound healing assays. Western blotting was employed to assess the expression of endometrial epithelial markers (CD9 and CK19) and stromal markers (Vimentin and CD13), alongside the phosphorylation status of JAK2 and STAT3. Dual-luciferase reporter assays were conducted to validate SDF2 and FGF7 as direct targets of miR-210-3p and miR-31-5p, respectively. Results Suppression of miR-210-3p and miR-31-5p significantly augmented the proliferative and migratory abilities of UCB-MSCs, while simultaneously enhancing their differentiation into endometrial epithelial cells and attenuating their transition into stromal cells. Concurrently, the phosphorylation levels of JAK2 and STAT3 were markedly elevated. Overexpression of SDF2 and FGF7 further amplified the proliferative, migratory, and epithelial differentiation capacities of UCB-MSCs, accompanied by heightened activation of the JAK2/STAT3 signaling pathway. Notably, SDF2 overexpression and FGF7 overexpression effectively counteracted the inhibitory effects exerted by miR-210-3p and miR-31-5p mimics on UCB-MSC proliferation, migration, and epithelial differentiation, mediated through the modulation of JAK2/STAT3 signaling. Conclusion miR-210-3p and miR-31-5p orchestrate the functional dynamics of UCB-MSCs by targeting SDF2 and FGF7, respectively, through the JAK2/STAT3 pathway. These findings unveil novel mechanistic insights into the regenerative potential of UCB-MSCs, offering promising avenues for therapeutic advancements in endometriosis.
Stem Cell Research & Therapy•2025•DOI: 10.1186/s13287-025-04396-1
Background One major factor contributing to infertility in women of childbearing age is premature ovarian insufficiency (POI). Exosomes produced from human umbilical cord mesenchymal stem cells (hUMSC-Exos) have drawn a lot of attention lately as a potential treatment for ovarian dysfunction brought on by POI. However, its therapeutic mechanism is still unclear and needs further exploration.
Methods POI model was established by intraperitoneal injection of cyclophosphamide (CTX) in female Wistar rats. These POI rats were treated with hUMSC-Exos for one week. In addition to in vivo experiments, in vitro POI models were also established. In vitro experiments, theca interstitial cells (TICs) treated with CTX were exposed to normal as well as let-7a-5p inhibitory hUMSC-Exos. The ovary structure, morphology, endocrine function, and reproductive ability of POI rats were observed by H&E staining and ELISA. Western blot, immunofluorescence staining (IF), and quantitative real-time polymerase chain reaction (qRT-PCR) were used to evaluate the autophagy-related indexes in ovary and TICs of POI rats in each group.
Results CTX induced abnormalities of ovarian morphology, structure, endocrine, and reproductive function in rats, and accompanied by autophagy of TICs. Notably, hUMSC-Exos diminishes ovarian structural and functional damage in POI rats and TICs autophagy via targeting the AMPK/mTOR pathway. Furthermore, downregulating let-7a-5p in hUMSC-Exos weakened their ability to prevent TICs autophagy.
Conclusions Overall, the findings suggested that hUMSC-Exos improves ovarian function in POI rats by inhibiting TICs autophagy via the let-7a-5p/AMPK/mTOR pathway. Our study provided further evidence that POI patients can benefit from hUMSC-Exos-mediated therapy.
Stem Cell Research & Therapy•2025•DOI: 10.1186/s13287-025-04727-2
Introduction Type 1 diabetes (T1D) results from the destruction of pancreatic β-cells, leading to insulin deficiency. As insulin therapy does not affect disease progression, advancements in immune regulation therapies have emerged, including the reconstitution of the insulin secretory system. Cysteine-rich acidic secretory protein (SPARC) is an extracellular matrix glycoprotein that regulates cell adhesion, facilitating cell migration, and mediating interactions between cells and their extracellular matrix. SPARC is overexpressed during tissue repair and is involved in β-cells survival. However, the potential of SPARC-modified mesenchymal stem cells (MSCs) to improve insulin secretion has not been thoroughly investigated. This study investigated the therapeutic effects of SPARC-MSCs in vivo and in vitro and assessed whether SPARC enhances survival and insulin secretion after β-cells injury. Methods In vivo, we established T1D models in mice and canine using SPARC-MSCs for cell transplantation. In vitro, MIN6 cells were damaged with STZ, and SPARC-MSC supernatant was co-cultured with MIN6 for various assays. Results Our study demonstrated that SPARC enhanced the regenerative capacity and migratory efficiency of MSCs after H2O2 injury and improved their morphology. In STZ-induced canine and mice diabetes models, SPARC-MSCs therapy significantly reduced hyperglycemia, improved oral glucose tolerance test (OGTT), and reversed weight loss in canine. Biochemical analyses showed improved liver function, and histological examination revealed restored islet area was significantly restored. Transcriptome and proteome sequencing indicated significant enrichment in calcium binding and cell migration pathways. Co-culturing SPARC-MSC supernatant with MIN6 cells after STZ injury restored their regenerative ability, enhancing insulin secretion and ATP content under high glucose stimulation. SPARC treatment also significantly increased intracellular Ca2+ levels in MIN6 cells. Conclusion SPARC significantly promotes cell regeneration and stimulates insulin secretion by increasing intracellular ATP and Ca2+ influx. In diabetic canine and mice models, it alleviated hyperglycemia, improved glucose tolerance, and enhanced pancreatic islet area and insulin secretion.
Stem Cell Research & Therapy•2024•DOI: 10.1186/s13287-024-03835-9
Background Facial infiltrating lipomatosis is characterized by excessive growth of adipose tissue. Its etiology is associated with somatic phosphatidylinositol 3-kinase catalytic subunit alpha (PIK3CA) variants, but the specific mechanisms are not yet fully understood. Methods We collected facial adipose tissue from both FIL patients and non-FIL individuals, isolated the stromal vascular fraction (SVF) and performed single-cell transcriptome sequencing on these samples. Results We mapped out the cellular landscape within the SVF, with a specific focus on a deeper analysis of fibro-adipogenic precursor cells (FAPs). Our analysis revealed that FAPs from FIL patients (FIL-FAPs) significantly overexpressed FK506 binding protein 51 (FKBP5) compared to FAPs from individuals without FIL. Further experiments indicated that FKBP5 is regulated by the PI3K-AKT signaling pathway. The overactivation of this pathway led to an increase in FKBP5 expression. In vitro experiments demonstrated that FKBP5 promoted adipogenic differentiation of FAPs, a process that could be hindered by FKBP5 knockdown or inhibition. Additionally, in vivo assessments confirmed FKBP5’s role in adipogenesis. Conclusions These insights into the pathogenesis of FIL underscore FKBP5 as a promising target for developing non-surgical interventions to manage the excessive adipose tissue growth in FIL.
Stem Cell Research & Therapy•2024•DOI: 10.1186/s13287-024-03938-3
Background: Despite the pivotal role of fat grafting in plastic, reconstructive, and aesthetic surgery, inconsistent survival rates of transplanted adipose tissue, primarily due to early ischemic and hypoxic insults, remain a significant challenge. The infusion of healthy mitochondria has emerged as a promising intervention to support tissue recovery from ischemic, hypoxic, and other types of damages across various organ systems. Objectives: This study aims to evaluate the impact of supplementing human adipose tissue grafts with healthy exogenous mitochondria on their volume and mass retention rates when transplanted into the subcutaneous layers of nude mice. This approach seeks to improve and optimize fat grafting techniques. Methods: Human adipose tissues were preconditioned with exogenous mitochondria (10 µg/mL), a combination of exogenous mitochondria and the inhibitor Dyngo-4a, Dyngo-4a alone, or PBS, and then transplanted into the subcutaneous tissue of 24 nude mice. Samples were harvested at 1 and 3 months post-transplantation for analysis of mass and volume retention. The structural morphology and integrity of the adipose tissues were assessed using Hematoxylin and Eosin (H&E) staining. Results: Mitochondrial preconditioning significantly enhanced the retention of mass and volume in fat grafts, demonstrating superior structural morphology and integrity compared to the control group. Conclusions: This study highlights the potential of exogenous mitochondrial augmentation in fat transplantation to significantly improve fat graft survival, thereby optimizing the success of fat grafting procedures.
Stem Cell Research & Therapy•2024•DOI: 10.1186/s13287-024-03908-9
Background The formation of stem cell clones enables close contact of stem cells inside. The gap junctions in such clone spheres establish a microenvironment that allows frequent intercellular communication to maintain self-renewal and functions of stem cells. Nevertheless, the essential gap junction protein for molecular signaling in clones is poorly known. Methods Primary human airway basal cells (hBCs) were isolated from brushing samples through bronchoscopy and then cultured. A tightly focused femtosecond laser was used to excite the local Ca2+ in an individual cell to initiate an internal Ca2+ wave in a clone to screen gap junction proteins. Immunoflourescence staining and clonogenicity assay were used to evaluate self-renewal and functions. RNA and protein levels were assessed by PCR and Western blot. Air–liquid interface assay was conducted to evaluate the differentiation potential. A Naphthalene injury mouse model was used to assess the regeneration potential. Results Herein, we identify Connexin 25 (Cx25) dominates intercellular Ca2+ communications in clones of hBCs in vitro to maintain the self-renewal and pluripotency of them. The self-renewal and in vitro differentiation functions and in vivo regeneration potential of hBCs in an airway damage model are both regulated by Cx25. The abnormal expression of Cx25 is validated in several diseases including IPF, Covid-19 and bronchiectasis. Conclusion Cx25 is essential for hBC clones in maintaining self-renewal and functions of hBCs via gap junctions.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2026030
The recombination-activating gene (RAG)-mediated V(D)J rearrangement mechanism is essential for generating the diversity of the adaptive immune system in jawed vertebrates. The RAG1 and RAG2 proteins form a tetrameric complex that recognizes and cleaves pairs of recombination signal sequences (RSSs). In jawed vertebrates, the N-terminal region of RAG1 and the C-terminal region of RAG2 are critical for the regulation of physiological function and enhancement of recombination accuracy. Moreover, the intracellular activity of RAG1/2 is rigorously regulated and is thought to represent the aspect shaped by host coevolution. However, these regulatory mechanisms remain incompletely understood, impeding our deeper understanding of the physiological functions of RAG. Previous studies have shown that jawed vertebrate RAG evolved from invertebrate RAG-like (RAGL) transposases and underwent key structural changes during evolution. RAGL genes have been identified in multiple invertebrate species, but from Branchiostoma belcheri (Bb), the RAG-like protein in Bb amphioxus (BbRAG1L) and the RAG2-like protein in Bb amphioxus (BbRAG2L) are among the most extensively characterized to date. Lancelets (amphioxus) represent the most basal extant chordates (cephalochordates) that diverged from the other two chordate lineages (urochordates and vertebrates). Consequently, amphioxus has been considered a “living fossil” for studying the origins and evolution of adaptive immunity. Homologs of the core structural domain of RAG1 were discovered in the amphioxus genome in 2005, and the homologs were subsequently shown to exhibit recombinase activity in cooperation with murine-derived RAG2. A large number of transposon genes were then identified in the amphioxus genome, followed by the identification of target site duplication (TSD) and terminal inverted repeat (TIR) sequences in the amphioxus genome. Notably, BbRAG2L lacks the C-terminal region present in murine RAG2, including the acidic hinge and PHD domain. BbRAG1L coupled with BbRAG2L displays significant transposition activity in vitro and in human cell lines. In contrast, vertebrate RAG exhibits limited transposon activity in vitro and extremely low transposon activity in vivo. This leads to the question of how RAG lost its transposase activity during evolution. Structural comparison and functional experiments of BbRAGL (protoRAG) and vertebrate RAG have revealed that vertebrates undergo essential adaptive changes to eliminate the primitive transposase activity of protoRAG. Research on BbRAGL has therefore provided strong support for the hypothesis that RAG originated from a domesticated transposon. Given the similarity in both structure and function between BbRAG1L and vertebrate RAG and the fact that BbRAGL proteins are the only RAGL proteins that can currently be efficiently expressed in vertebrate cells, characterizing the binding partners of BbRAGL involved in amphioxus is of great significance for understanding the regulation of BbRAGL and its adaptation and evolution. Parallel comparison of BbRAGL and RAG interaction networks may further clarify how BbRAGL transitioned from a transposase to a recombinase during host coevolution and reveal general principles of vertebrate intracellular RAG regulation. In recent years, proximity labeling techniques have greatly facilitated approaches to identifying RAG cofactors. For example, RAG1 fused to biotin ligase RAG1 fused to a biotin ligase found in Escherichia coli (BirM) has been used to define dynamic interaction networks of RAG-associated proteins. Inspired by these advances, we sought to apply a similar approach to identify the BbRAGL cofactors in amphioxus and build a regulatory network of BbRAGL that could shed light on its relationship with host evolution. However, endogenous BbRAGL expression is undetectable in the adult amphioxus (data not shown), and the generation of transgenic amphioxus lines expressing proximity-based labeling proteins remains technically challenging. These constraints make it difficult to analyze native cofactors of endogenous BbRAGL in vivo. Because BbRAGL can be expressed in vertebrate cell lines, we instead developed an in vitro proximity-labeling strategy. We fused TurboID (TbID), an engineered biotin ligase, to the N-terminus of BbRAG1L or BbRAG2L (Figure 1A), purified the fusion proteins, and incubated them with protein lysates prepared from the hepatic cecum and colons of adult B. belcheri amphioxus in vitro to label the interacting proteins. The proteins were finally analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) (Figure 1B). A pTT5 vector was used to express plasmids encoding maltose-binding protein (MBP) and TurboID with or without full-length BbRAG1L or BbRAG2L, yielding pTT5-MBP-TurboID, pTT5-MBP-TurboID-BbRAG1L, and pTT5-MBP-TurboID-BbRAG2L. Plasmids expressing MBP-BbRAG1L and MBP-BbRAG2L were also generated.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025148
Mesothelial cells play an important role in colorectal cancer peritoneal metastasis (CRC-PM), where they support tumor growth and invasion. In this study, we investigate the molecular mechanisms by which mesothelial cells contribute to CRC metastasis. Using single-cell RNA sequencing (scRNA-seq) on tissue samples from 12 CRC patients with peritoneal metastasis, we identify PDK4 as a key gene in mesothelial cells during metastasis. The expression of PDK4 is significantly greater in mesothelial cells undergoing mesothelial-to-mesenchymal transition (MMT) compared to normal peritoneal cells, suggesting its involvement in mesothelial cell reprogramming during peritoneal metastasis. In vitro experiments show that coculturing mesothelial cells with CRC cells leads to increased PDK4 expression, which in turn enhances mesothelial cell migration and invasion. Knockdown of PDK4 reduces mesothelial cell invasion, while overexpression of PDK4 increases invasive ability, highlighting its critical role in mesothelial cell invasion. Additionally, PDK4 promotes metabolic changes, specifically increasing fatty acid oxidation (FAO), which is necessary for mesothelial cell invasion. Blocking FAO reduces the invasive ability of PDK4-overexpressing mesothelial cells, while restoring FAO in PDK4-knockdown cells rescues their invasion potential. Further analysis shows that PDK4 enhances the acetylation of β-catenin, a protein involved in cell movement, and that this modification is crucial for mesothelial cell invasion. Our results suggest that PDK4 regulates mesothelial cell invasion through β-catenin acetylation following metabolic reprogramming, offering a potential target for therapies aimed at inhibiting CRC-PM.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025063
Homologous recombination (HR) is crucial for the high-fidelity repair of DNA double-strand breaks (DSBs), ensuring the maintenance of genome stability. In this study, we show that FOXD3 interacts with poly (ADP-ribose) polymerase 1 (PARP1) and is recruited to DSBs in a PARP1-dependent manner. FOXD3 directly binds to the DSB repair protein MRE11 and promotes its recruitment to DSB sites, ensuring proper end resection. Inhibition of FOXD3 expression compromises HR-mediated DSB repair and chromosome stability and sensitizes cancer cells to ionizing radiation. Collectively, our findings demonstrate that FOXD3 promotes HR-mediated DSB repair and genome stability.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025070
Schisandrin A (SchA), a bioactive lignan that was isolated from the dried fruit of Schisandra chinensis, has attracted much attention because of its diverse spectrum of pharmacological effects. The aim of this study is to clarify the function of SchA in diabetes-related fear memory impairment and its molecular mechanisms. Rats are randomly assigned to 4 groups: the control group (Con group), the DM group, the DM + SchA group, and the Con + SchA group. The results demonstrate that SchA treatment improves insulin sensitivity, reduces blood glucose, and significantly reduces memory impairment. SchA treatment also prevents histological damage, enhances synaptic protein production, and significantly decreases Aβ42 formation in the diabetic prefrontal cortex. Further research reveals that SchA therapy decreases microglial activation and the expression levels of variables linked to inflammation while increasing the phosphorylation of proteins implicated in the insulin resistance signaling pathway. Furthermore, in the prefrontal cortex of diabetic rats, SchA decreases ferroptosis by increasing the protein expressions of GPX4, SLC7A11, Nrf2, HO-1, and SIRT1. Overall, our findings suggest that SchA may lessen diabetes-associated fear memory impairment symptoms by, most likely, lowering ferroptosis and inflammatory responses in the prefrontal brain of diabetic rats. SchA may be a useful therapy for diabetes, including memory impairment.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025193
Arsenic, a toxic metalloid, exists in organic or inorganic states within the Earth’s seawater, river water, soil, atmosphere, food sources, and diverse biological tissues [1]. It poses a threat to the health of hundreds of millions of people globally [2]. Arsenic exposure has toxic effects on the cardiovascular system of organisms, thus endangering human health [3]. Research has indicated that the harmful effect of arsenic exposure on the heart is associated with abnormal calcium handling in myocardial cells [4]. The cardiac ryanodine receptor type 2 (RyR2) is a primary channel involved in the surface of the endoplasmic reticulum in cardiac myocytes that regulates the release of Ca2+ during the systolic phase [5]. The integrity of its function is crucial for maintaining calcium homeostasis in cardiac myocytes. However, when myocardial tissue is damaged and undergoes pathological changes, the spatial structure of the RyR2 protein becomes unstable and becomes excessively activated, thereby triggering Ca2+ leakage [6]. Dantrolene (Dan), which serves as a stabilizer of RyR1, is frequently employed in clinical settings for the treatment of malignant hyperpyrexia and relieves spastic muscle tension [7]. Previous studies have demonstrated that dantrolene also has a stabilizing effect on RyR2 [8]. Research has shown that dantrolene can prevent calcium leakage in myocardial cells by stabilizing the tertiary structure of the RyR2 protein and thereby inhibiting the pathological hyperactivity of RyR2 [9]. Therefore, this study hypothesizes that dantrolene, by virtue of this stabilizing effect, can alleviate myocardial injury caused by arsenic exposure to some extent and plays a role in protecting cardiac function. For this purpose, we established an arsenic exposure model and a Dan intervention arsenic exposure model to verify the protective effect of Dan on the myocardial tissue and cardiac function of arsenic-exposed rats.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025039
Cadmium (Cd) is a high-risk heavy metal that induces oxidative stress, endoplasmic reticulum (ER) stress and inflammation, damaging organs such as the liver. Puerarin (PUE) has been shown to treat liver injury and especially prevent Cd-induced hepatic damage via its antioxidant activity. Sirtuin 1 (SIRT1), a histone deacetylase, is a key protector against various stress insults. However, its role in the protection of PUE against Cd-induced liver damage has not been clarified. Thus, this study is designed to elucidate the molecular mechanism in the human hepatoma cell line HepG2. The results first reveal that Cd-induced apoptosis is significantly restored by PUE pretreatment, as confirmed by the CCK-8, flow cytometric, Hoechst 33258 and TUNEL assays. Mechanistically, PUE significantly decreases ROS production and increases SOD levels in Cd-treated HepG2 cells. Moreover, PUE pretreatment alleviates ER stress by inhibiting the PERK-eIF2α-ATF4-CHOP axis and subsequently partially restores ER function as revealed by decreased Ca2+ release from the ER. In addition, further study demonstrates that PUE upregulates SIRT1 expression, which suppresses the PERK signaling cascade and reduces CHOP levels. Collectively, our results first demonstrate that PUE protects HepG2 cells from Cd-induced apoptosis at least partially by inhibiting the PERK-eIF2α-ATF4-CHOP pathway in a SIRT1 expression-dependent manner. Puerarin appears to have great potential as a hepatoprotective agent.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025152
Tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB), remains a significant global health threat. However, the licensed Bacille Calmette-Guérin (BCG) vaccine provides only limited protection in adults, underscoring the urgent need for more effective preventive strategies. Recent studies have shown that multi-epitope DNA vaccines are superior to traditional vaccines in terms of immunogenicity, safety and stability. In this study, we develop a multi-epitope DNA vaccine that contains CD8+ T-cell epitopes, CD4+ T-cell epitopes, and B-cell epitopes using bioinformatics tools. These epitopes are derived from three genome-encoded proteins, ESAT-6, Rv2660c, and RpfB, which exhibit stage-specific immunodominance in the early, resting, and convalescent stages of MTB infection. Using reverse vaccinology and computational immunomodulation, we demonstrate that the multiepitope vaccine increases antigen-specific antibody titres, activates CD8+ T and CD4+ T cells, and enhances IFN-γ secretion. In vitro validation studies in HEK293T cells confirm high-yield expression of multi-epitope-encoded antigens, whereas in vivo immunization experiments reveal significant expansion of NK cells and Th1-polarized lymphocytes, with concomitant upregulation of pro-inflammatory mediators. Collectively, these results highlight the potent activation of adaptive immunity through Th1-driven mechanisms and IFN-γ-mediated mycobacterial clearance, which are crucial for defending against MTB.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025176
The iron regulatory protein IREB2 (Iron Responsive Element Binding Protein 2) plays a crucial role in maintaining cellular iron homeostasis through the posttranscriptional regulation of genes involved in iron metabolism. Mutations in the IREB2 gene have been linked to NDCAMA (OMIM#618451), a rare genetic neurological disorder characterized by early-onset neurodegeneration, choreoathetoid movements, and microcytic anemia. However, the absence of an IREB2-mutated animal model has left the underlying pathogenic mechanisms poorly understood. To investigate this, we establish a CRISPR-Cas9-mediated Ireb2D826V/D826V mouse model, which carries the c.2477A>T (p.D826V) pathogenic variant in IREB2 identified in a Chinese pedigree with NDCAMA. Behavioral studies, including the Morris water maze (MWM), open field test (OFT), and Y-maze, reveal significant neurobehavioral deficits, such as impaired spatial learning and memory and reduced motor activity, in Ireb2D826V/D826V mice. Furthermore, we observe increased microglial activation and decreased dendritic spine density in the hippocampus, along with impaired long-term potentiation (LTP) and elevated paired-pulse facilitation (PPF), indicating synaptic dysfunction. Mechanistically, Ireb2D826V/D826V mice present reduced Ireb2 protein levels, dysregulated iron metabolism, and an altered expression profile associated with neurological function. This study elucidates the molecular mechanisms underlying NDCAMA and establishes Ireb2D826V/D826V mice as a model for iron metabolism-driven neurodegeneration. This finding links the instability of IREB2 to synaptic failure and neuroinflammation, highlighting potential therapeutic implications for neurodegenerative diseases.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025207
O-GlcNAcylation, a prevalent reversible post-translational modification, intricately alters non-histone proteins, influencing the organization of gene transcriptional regulation within the accessible chromatin environment. This nucleoplasmic landscape, characterized by histone-free regions, fundamentally enables O-GlcNAc-mediated modulation through dynamic accessibility. However, unraveling the O-GlcNAc-open chromatin interplay that governs sophisticated transcriptional regulatory networks remains constrained by current techniques, which lack the resolution to probe this spatiotemporal crosstalk. Here, we report a general strategy to systematically and chemoselectively profile O-GlcNAc-associated chromatin accessibility on a genome-wide scale (COCA-seq). Through comprehensive validation across low- and high-throughput levels, we demonstrate COCA-seq’s dual fidelity in both O-GlcNAc chemoselectivity and open chromatin specificity. We employ it to delve into doxorubicin resistance for breast cancer, scrutinizing pivotal regulatory genes and transcription factors implicated in this complex biological event. By integrating bulk RNA-seq with COCA-seq, we offer a multiomics perspective, shedding light on related biological processes and pathways like drug efflux and stress homeostasis, thereby uncovering potential mechanisms by which O-GlcNAc-associated open chromatin orchestrates tumor drug resistance. COCA-seq emerges as a general and versatile tool across various biological contexts, poised to reveal the landscape of O-GlcNAc-associated open chromatin regions across the genome and decipher the significance of glycosylation behind it.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025212
Spatial biology aims to elucidate cellular organization, function, and interactions within native tissue contexts, offering key insights into both normal physiology and disease. Spatial proteomics complements this by enabling high-resolution mapping of protein localization and abundance, directly reflecting functional cellular states. Unlike transcriptomics, which infers potential activity, proteomics captures actual molecular functions, including post-translational modifications and dynamic interactions. However, in situ protein profiling poses significant challenges, as proteins cannot be directly sequenced or easily targeted via nucleic acid hybridization. Antibody-oligonucleotide conjugates (AOCs) address this limitation by converting protein recognition into a DNA-based readout, thereby enabling sensitive and scalable detection. In this review, we outline the core principles of AOC-based spatial proteomic technologies, including multiplexed protein analysis, in situ protein-protein interactions, and integration with other biomolecular data. We highlight their applications in decoding tissue complexity and disease pathology and examine key technical challenges that remain. Overall, AOCs offer distinct advantages, including DNA-mediated signal amplification, spatially resolved proteomic profiling, and compatibility with multi-omics approaches, positioning them as powerful platforms in the advancement of spatial biology.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025183
Hepatocyte phospholipase D1 (PLD1) knockout alleviates metabolic dysfunction-associated steatotic liver disease (MASLD) in mice, but the underlying mechanism is largely unknown. In this study, the mice are divided into four groups: Con (wild-type mice with normal control diet), HFHC (wild-type mice with high-fat diet), Con_KO (hepatocyte PLD1-knockout mice with normal control diet), and HFHC_KO (hepatocyte PLD1-knockout mice with high-fat diet). Intestinal contents of mice are analyzed via metagenomics and metabolomics, and the liver bile acids are assessed by mass spectrometry imaging. The results show that at the phylum level the abundance of Bacillota in the intestines of MASLD model mice is significantly increased, whereas that of Bacteroidota significantly is decreased. However, after the deletion of hepatocyte PLD1, Pseudomonadota and Candidatus Bathyarchaeota are significantly decreased in the MASLD model mice. At the species level, compared with that in the Con group, the abundance of Faecalibaculum rodentium is significantly increased in the HFHC group, whereas hepatocyte PLD1 knockout causes the abundances of Desulfovibrionaceae bacterium LT0009 and Lachnospiraceae bacterium 10-1 to be significantly decreased. In terms of intestinal bile acids, the levels of two bile acids (hyodeoxycholic acid and glycolithocholic acid) differ between the HFHC_KO group and the HFHC group. Association analysis shows that Faecalibaculum co-occurs with DCA, βMCA, ΩMCA and αMCA, while probiotic Bacteroides uniformis is significantly correlated with UDCA, 12-KetoLCA, and 7-KetoLCA. Finally, mass spectrometry imaging reveals that the TCA and TDCA contents in the liver are significantly decreased after PLD1 knockout in hepatocytes. These findings demonstrate that hepatocyte PLD1 knockout alters the gut microbiota and bile acids profiles, suggesting that PLD1 deficiency may modulate MASLD progression by changing intestinal microbiota-bile acid homeostasis.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025230
The diverse antibodies of adaptive immunity comprise an antibody repertoire that combats various pathogens. This repertoire is shaped by both intrinsic antibody gene diversification and extrinsic cellular selection. Conversely, an antibody repertoire contains multiple layers of immunological information, including the history of pathogen exposure. High-throughput sequencing-based antibody repertoire cloning approaches have revealed unexpected features of adaptive immunity. However, our understanding of antibody repertoire data is still in its infancy. In this review, we introduce the emerging concepts and discuss the application of deep learning approaches to understanding antibody repertoires. First, we introduce the definition and functional features of antibody clonotype. Next, we review the evolution of antibody clonotypes and discuss potential antibody repertoire-directed vaccination approaches. Lastly, we summarize the application of deep learning in predicting antibody binding, generating specific antibodies, and making immunologic diagnoses. Recently, artificial intelligence (AI) has made revolutionary progress in biology. Leveraging high-dimensional antibody repertoire information, deep learning models have the potential to transform our understanding of antibody repertoire.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2026081
Multiple myeloma (MM) patients frequently experience relapse, disease progression, and drug resistance, necessitating novel therapeutic strategies. This study investigates the role of peptidylprolyl isomerase A (PPIA) in mediating dihydroartemisinin (DHA)-induced ferroptosis in MM. Building on our previous work establishing the prognostic relevance of ferroptosis in MM, we elucidate the mechanism by which DHA triggers this form of cell death through the disruption of iron metabolism and redox homeostasis. DHA significantly reduces the viability of MM cell lines and primary CD138+ cells derived from patient bone marrow samples and attenuates tumor burden in orthotopic MM models. Mechanistically, DHA upregulates the iron-regulatory genes transferrin receptor 1 (TFRC) and heme oxygenase-1 (HMOX1), thereby perturbing iron homeostasis and promoting ferroptosis. Crucially, DHA targets the oxidized form of PPIA, a redox-sensitive chaperone, binding to it and preventing its reduction, which elevates intracellular reactive oxygen species (ROS). Combined treatment with DHA and erastin, which concurrently disrupt iron and amino acid metabolism, exerts synergistic cytotoxicity and enhances MM inhibition. Furthermore, in a syngeneic mouse model, DHA promotes T-cell activation and augments tumor suppression. Collectively, these findings underscore PPIA’s pivotal role in a novel ferroptotic cell death pathway and reveal new therapeutic opportunities for MM.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2026074
Tryptophan (Trp)-substituted antimicrobial peptides (AMPs) exhibit enhanced interactions with bacterial cell membranes, potentially improving their antimicrobial efficacy. Klebsiella pneumoniae (20.59% of 2054 ICU isolates) is resistant to multiple clinically used antibiotics and presents significant treatment challenges. In the present study, three Trp-modified peptides (I4W, L12W, and I1WL5W) are generated by substituting Ile or Leu residues in temporin-1CEb, a peptide derived from frog skin, with Trp at various sites to assess their antibacterial effects and mechanisms against K. pneumoniae. Compared with L12W, both I4W and I1WL5W display superior antimicrobial activity and lower cytotoxicity. Mechanistic studies reveal that AMPs exert antibacterial and bactericidal effects through bacterial surface charge neutralization, insertion into bacterial cell membranes, increase permeability of both the inner and outer membranes, and disruption of membrane integrity. Notably, I1WL5W exhibit the most potent membrane-disrupting activity. Assessment of the impact of Trp-containing peptides on bacterial biofilms reveals that these peptides not only inhibit exopolysaccharide production and biofilm formation but also degrade preformed biofilms. A murine lung infection model is established to investigate the therapeutic efficacy of I1WL5W against MDRKP 1203-induced lung infection in mice. Compared with the control treatment, treatment with I1WL5W results in reduced bacterial counts and levels of IL-6 and TNF-α in both the blood and lung tissues of MDRKP 1203-infected mice, and treatment with I1WL5W improves lung tissue structure. The present study provides valuable insights for designing Trp-containing peptides with potent antimicrobial properties by facilitating their penetration across bacterial membranes.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024134
SUN5, a testis-specific gene, is associated with acephalic spermatozoa syndrome (ASS). Here, we demonstrate that SUN5 is involved in mRNA export. In Sun5-knockout mice (Sun5–/–), poly(A)+ RNA accumulates in the nuclei of germ cells, leading to reduced sperm counts, decreased sperm motility and disrupted sperm head-to-tail junctions. Additionally, in the GC-2 germ cell line with RNA interference of Sun5, heterogeneous nuclear ribonucleoproteins (hnRNPs) and poly (A)+ RNA (mainly mRNA) are retained in the nucleus. Further mechanistic studies reveal that SUN5 interacts with Nxf1 (nuclear RNA export factor 1) and nucleoporin 93 (Nup93). Interference with Nup93 inhibits mRNA export. Treatment with leptomycin B to block the CRM1 pathway indicates that Sun5 regulates mRNA export through an Nxf1-dependent pathway. In Sun5–/– mice, the binding of Nxf1 and Nup93 decreases due to loss of Sun5 function, and the process of submitting Nxf1-binding mRNPs to Nup93 is inhibited, resulting in abnormal spermatogenesis. Together, these data may elucidate a novel pathway for mRNA export in male germ cells.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024090
MicroRNAs (miRNAs) are implicated in the development of cancers and may serve as potential targets for therapy. However, the functions and underlying mechanisms of miRNAs in cancers are not well understood. This work aims to study the role of miR-373-3p in colon cancer cells. We find that the expression of miR-373-3p mimics promotes and the miR-373-3p inhibitor suppresses aerobic glycolysis and proliferation of colon cancer cells. Mechanistically, miR-373-3p inhibits the expression of MFN2, a gene that is known to suppress glycolysis, which leads to the activation of glycolysis and eventually the proliferation of cells. In a nude mouse tumor model, the expression of miR-373-3p in colon cancer cells promotes tumor growth by enhancing lactate formation, which is inhibited by the co-expression of MFN2 in the cells. Administration of the miR-373-3p antagomir blunts in vivo tumor growth by decreasing lactate production. In addition, in human colon cancers, the expression levels of miR-373-3p are increased, while those of MFN2 mRNA are decreased, and the increase of miR-373-3p is associated with the decrease of MFN2 mRNA. Our results reveal a previously unknown function and underlying mechanism of miR-373-3p in the regulation of glycolysis and proliferation in cancer cells and underscore the potential of targeting miR-373-3p for colon cancer treatment.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024073
Chikungunya virus (CHIKV) is a neglected arthropod-borne and anthropogenic alphavirus. Over the past two decades, the CHIKV distribution has undergone significant changes worldwide, from the original tropics and subtropics regions to temperate regions, which has attracted global attention. However, the interactions between CHIKV and its host remain insufficiently understood, which dampens the need for the development of an anti-CHIKV strategy. In this study, on the basis of the optimal overexpression of non-structural protein 4 (nsP4), we explore host interactions of CHIKV nsP4 using mass spectrometry-based protein-protein interaction approaches. The results reveal that some cellular proteins that interact with nsP4 are enriched in the ubiquitin-proteasome pathway. Specifically, the scaffold protein receptor for activated C kinase 1 (RACK1) is identified as a novel host interactor and regulator of CHIKV nsP4. The inhibition of the interaction between RACK1 and nsP4 by harringtonolide results in the reduction of nsP4, which is caused by the promotion of degradation but not the inhibition of nsP4 translation. Furthermore, the decrease in nsP4 triggered by the RACK1 inhibitor can be reversed by the proteasome inhibitor MG132, suggesting that RACK1 can protect nsP4 from degradation through the ubiquitin-proteasome pathway. This study reveals a novel mechanism by which the host factor RACK1 regulates CHIKV nsP4, which could be a potential target for developing drugs against CHIKV.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024084
Osteosarcoma (OS) is a primary bone cancer mostly found in adolescents and elderly individuals. The treatment of OS is still largely dependent on traditional chemotherapy. However, the high incidence of drug resistance remains one of the greatest impediments to limiting improvements in OS treatment. Recent findings have indicated that the transcription factor FOXM1 plays an important role in various cancer-related events, especially drug resistance. However, the possible role of FOXM1 in the resistance of OS to methotrexate (MTX) remains to be explored. Here, we find that FOXM1, which confers resistance to MTX, is highly expressed in OS tissues and MTX-resistant cells. FOXM1 overexpression promotes MTX resistance by enhancing autophagy in an HMMR/ATG7-dependent manner. Importantly, silencing of FOXM1 or inhibiting autophagy reverses drug resistance. These findings demonstrate a new mechanism for FOXM1-induced MTX resistance and provide a promising target for improving OS chemotherapy outcomes.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024042
Lotus seed skin extract is rich in flavonoids, making it a promising candidate for developing health products. In a previous study, we found that proanthocyanidins from lotus seed skin, particularly proanthocyanidin B1 (PB1), can indirectly activate the Nrf2 signaling pathway, exerting an antioxidant effect. In this study, we isolate proanthocyanidins from lotus seed skin (PLS) using ethanol extraction and RP-HPLC identification, and investigate its effects on glycolipid metabolism both in vivo and in vitro. Our results demonstrate that PLS reduces body weight in high-fat diet (HFD) mice by decreasing feed efficiency. PLS also normalizes serum glucose, insulin secretion, glycosylated hemoglobin (HbA1c), and intraperitoneal glucose tolerance (IPGTT). Furthermore, PLS significantly improves blood lipid parameters and inhibits the expressions of six proinflammatory factors, including IL-1α, IL-1β, IL-3, IL-6, IFN-γ and TNF-α in HFD mice. Additionally, analysis of fresh liver tissues reveals that PLS and PB1 induce the expressions of antioxidant proteins such as HO-1 and NQO1 by activating the p38-Nrf2 signaling pathway and inhibiting the NF-κB signaling pathway. In conclusion, proanthocyanidins from lotus seed skin regulate glycolipid metabolism disorders by targeting the p38/Nrf2/NF-κB signaling pathway. Our study offers a new approach for the high-value comprehensive utilization of lotus seed skin by-products and precise dietary intervention for metabolic syndrome.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025105
This review delves into the crosstalk network between oligodendrocytes and other glial cells in the context of demyelinating diseases. Oligodendrocytes, the myelin-forming cells in the central nervous system (CNS), are crucial for maintaining the function and integrity of axons and myelin sheaths. In demyelination pathologies, various factors hinder the normal differentiation of oligodendrocyte precursor cells, obstructing the myelin regeneration process, which is a primary barrier to therapeutic myelin repair. Emerging evidence highlights the critical role of glial cell interactions in CNS homeostasis and myelin regeneration, increasing interest in the treatment of demyelinating diseases. This article reviews the role of interactions between oligodendrocytes and other CNS glial cells in demyelinating and neurological diseases. Previous findings suggest that other CNS glial cells influence the survival and metabolic activity of oligodendrocytes through cell interactions, significantly affecting myelin formation and impacting demyelinating diseases characterized by myelin regeneration disorders. Targeted modulation of oligodendrocytes and their interactions with other cells at specific temporal stages may indicate a novel therapeutic direction for demyelinating diseases and offer fresh perspectives on the study of mechanisms and therapeutic approaches for related neurological conditions.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2024204
SMARCB1 encodes a core subunit of the SWI/SNF chromatin remodeling complex, which plays a crucial role in the regulation of gene expression. Germline mutations in the SMARCB1 gene have been linked to early childhood Coffin-Siris syndrome type 3 (CSS3), a rare congenital malformation syndrome characterized by severe developmental delay and intellectual disability. In this study, we report a family of two adult CSS3 patients with a novel missense SMARCB1 mutation (c.1091A>C, p.Lys364Thr) identified through whole-exome sequencing (WES). Both patients exhibit selective difficulties in verbal learning and experience language delays. Additionally, the development of meningioma is confirmed in one of the patients. Mechanistic studies suggest that this missense mutation may abnormally activate the MAPK signaling pathway, which is implicated in the pathogenesis of tumor progression and neurodevelopmental disorders. This is the first reported case of a germline mutation in the SMARCB1 gene associated with both CSS3 and meningioma, thereby expanding the phenotypic spectrum of SMARCB1-related disorders.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2024225
Arsenic is widely present in nature, and its compounds are extensively used in industrial, agricultural, and medical fields. Arsenic trioxide (As2O3) is specifically used as a therapeutic agent for acute promyelocytic leukemia because it induces cancer cell differentiation and apoptosis, significantly reduces the cancer cell count and has unique medical value. However, owing to its high toxicity and carcinogenicity, long-term use can induce cardiovascular diseases such as arrhythmia and myocardial contractile dysfunction. However, research on the treatment of arsenic-induced cardiotoxicity remains relatively scarce. Notably, artemisinin has anti-inflammatory and antioxidative effects on various heart diseases, effectively inhibiting reactive oxygen species (ROS) production, preventing myocardial damage and apoptosis caused by arsenic poisoning, and improving cardiac contractile and diastolic functions, thus enhancing cardiac function. This study aims to discuss the impact of artemisinin on the myocardium of arsenic-poisoned rats. Forty 12-week-old male SD rats were randomly divided into five groups: control, arsenic poisoning, drug control, low-dose artemisinin, and high-dose artemisinin. As2O3 was intraperitoneally injected at 5 mg/kg/day for 10 days in the arsenic poisoning, low-dose, and high-dose groups, whereas the control and drug control groups received equal volumes of physiological saline. Artemisinin was subsequently injected at corresponding doses for three weeks. Myocardial contrast echocardiography (MCE) was used to assess myocardial blood perfusion. Blood and myocardial tissue samples were collected for biochemical and histological analyses. Results showed that arsenic poisoning significantly decreased myocardial blood perfusion (AUC and WIS×PI) and increased CD31 expression, indicating microvascular damage and inflammation. Artemisinin intervention, especially at high dose, restored perfusion and reduced CD31 expression, suggesting a protective effect. Electron microscopy confirmed that artemisinin alleviated arsenic-induced myocardial structural damage. These findings suggest that artemisinin alleviates arsenic-induced myocardial injury by modulating oxidative stress and inflammatory responses.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025012
Pyroptosis is a regulated inflammatory cell death process that plays an essential role in various diseases. This study investigates the role of proline/serine-rich coiled-coil protein 1 (PSRC1) in pyroptosis and inflammation in macrophages. This study reports that PSRC1 expression is decreased in pyroptotic macrophages and that knockout of PSRC1 exacerbates pyroptosis and inflammation. PSRC1 overexpression alleviates pyroptosis and inflammation in macrophages. RNA-seq analysis reveals that PSRC1 regulates the expression of genes involved in the extracellular matrix (ECM). Specifically, PSRC1 downregulates the expression of periostin (POSTN), an ECM component. Knockdown of POSTN suppresses macrophage pyroptosis mediated by low expression of PSRC1. These findings suggest that PSRC1 can alleviate pyroptosis and inflammation in bone marrow-derived macrophages (BMDMs) by regulating the ECM and negatively regulating POSTN. This study provides insights into the role of PSRC1 in macrophage pyroptosis and identifies a potential target for the treatment of inflammatory diseases. Further research is needed to confirm these findings in vivo and in various disease models.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025098
Pathological myocardial hypertrophy, often caused by hypertension, is a well-established independent risk factor for heart failure. SBK3, a gene selectively expressed at relatively high levels in cardiac tissues, has an unclear functional role in the heart. This study is designed to examine the role of SBK3 in transverse aortic constriction (TAC)-induced heart failure, aiming to identify a novel mitochondrion-targeted therapeutic strategy for heart failure. The subcellular localization of SBK3 in adult rat cardiomyocytes is investigated by western blot analysis and immunofluorescence staining, which reveal that SBK3 is located in the mitochondria. Subsequent western blot analysis shows that SBK3 protein expression is downregulated under pathological hypertrophy. To assess the functional relevance of this observation, SBK3 is overexpressed both in vivo (via cardiac-specific AAV9-cTNT) and in vitro (via adenoviral transduction). In vitro, adenovirus-mediated overexpression of SBK3 significantly inhibits ANP and BNP expression and increases the Ca2+ transient amplitude in angiotensin II (Ang II)-induced hypertrophic cardiomyocytes. In vivo, cardiac-specific SBK3 overexpression using cTNT promoter-containing adeno-associated virus 9 inhibits TAC-induced cardiac hypertrophy and heart failure. Mechanistically, SBK3 exerts its cardioprotective effects by preserving the mitochondrial ultrastructure and regulating the balance of respiratory chain complexes. In addition, SBK3 modulates key regulators of mitochondrial dynamics, including fission and fusion proteins, thereby contributing to mitochondrial integrity and protection against pathological cardiac remodeling.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025038
Hepatocellular carcinoma (HCC) is a highly fatal form of malignancy that seriously threatens patient survival. The global 5-year survival rate for HCC patients ranges from 15% to 19%, and nearly 80% of patients are diagnosed at an advanced stage. Therefore, exploring the mechanism of HCC development and identifying biomarkers and therapeutic targets for HCC are vital. MicroRNAs (miRNAs), a class of noncoding single-stranded RNAs, are 20–24 nucleotides (nt) long. They play pivotal roles in modulating the progression of diverse diseases. The specific role of miR-32-5p in the development of HCC remains unclear. In this study, qRT-PCR is utilized to precisely determine the downregulated expression levels of miR-32-5p in HCC. Subsequently, functional analysis reveals the suppressive role of miR-32-5p in modulating the proliferative and migratory capabilities of HCC cells. Glycogen synthase kinase 3β (GSK3β) has emerged as a potential target of miR-32-5p, which is confirmed through a dual-luciferase reporter assay. Notably, the expression of GSK3β in HCC tissue specimens is negatively correlated with the abundance of miR-32-5p, and patients with high GSK3β expression have shorter survival time. Furthermore, the targeted downregulation of GSK3β remarkably impedes the proliferation and migration of tumor cells. This study suggests that miR-32-5p inhibits the proliferation and migration of HCC through regulating the GSK3β/NF-κB signaling pathway. Therefore, this study reveals that miR-32-5p exerts its suppressive effect on HCC progression, suggesting that it is a promising target for both diagnostic and targeted therapeutic interventions against HCC.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2024153
Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant disease with a poor prognosis, and the lack of effective treatment methods accounts for its high mortality. Pancreatic stellate cells (PSCs) in the tumor microenvironment play an important role in the development of PDAC. Previous studies have reported that patients with PDAC are more vulnerable to ferroptosis inducers. To investigate the relationship between PSCs and pancreatic cancer cells, a coculture system is used to further reveal the influence of PSCs on ferroptosis resistance in PDAC using many in vitro and in vivo experiments. Our results show that PSCs promote ferroptosis resistance in pancreatic cancer cells. We further demonstrate that IL15 secretion by PSCs activates the IL15RA-STAT3-GPX4/ACSL3 axis. The simultaneous upregulation of GPX4 and ACSL3 prevents lipid peroxidation and ultimately protects pancreatic cancer cells from ferroptosis both in vitro and in vivo. This study demonstrates that PSCs protect pancreatic cancer cells in a paracrine manner and may indicate a novel strategy for the treatment of PDAC.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2024185
Circular RNAs play a pivotal role in the progression of various cancers. In our previous study, we observed high expression of the circRNA MALAT1 (cMALAT1) in intrahepatic cholangiocarcinoma (ICC) cells co-incubated with activated hepatic stellate cells. This study is designed to explore the roles of cMALAT1 and the underlying mechanisms in ICC. We find that cMALAT1 significantly facilitates the progression of ICC both in vitro and in vivo. The binding between cMALAT1 and miR-512-5p is subsequently confirmed through RNA pull-down experiments. As anticipated, the application of miR-512-5p mimics noticeably reverses the cMALAT1 overexpression-induced malignant phenotypes of ICC cells. Furthermore, VCAM1 is identified as a downstream gene of the cMALAT1/miR-512-5p axis. Importantly, silencing of VCAM1 not only effectively suppresses the malignant phenotypes of ICC cells but also significantly impairs the functions of cMALAT1. Our study reveals that cMALAT1 promotes the progression of ICC by competitively binding to VCAM1 mRNA with miR-512-5p, leading to the upregulation of VCAM1 expression and the activation of the PI3K/AKT signaling pathway.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025147
CD47, a cell surface transmembrane glycoprotein, is an innate immune checkpoint that suppresses phagocytic clearance. Emerging evidence suggests that CD47 has noncanonical functions. However, its involvement in chemotherapy resistance is not well understood. Our study reveals that cisplatin treatment upregulates CD47 expression across multiple cancer cell lines. Cisplatin induces the expression of CD47 through the ATM/NF-κB signaling pathway. Genetic ablation of CD47 dramatically sensitizes cancer cells to cisplatin. Mechanistically, CD47 depletion potentiates cisplatin-induced DNA damage, as demonstrated by elevated γH2AX formation and ATM phosphorylation. Knockdown of CD47 inhibits the expression of DNA repair genes ERCC1, FANCA, and BRCA2 through the ATM/NF-κB pathway. Remarkably, CD47 blockade with neutralizing antibodies recapitulates these effects, synergistically potentiating cisplatin’s DNA-damaging capacity while suppressing DNA repair capacity. CD47 blockade also potentiates cisplatin’s tumor inhibitory effect in vivo. These findings establish a novel mechanism whereby CD47 promotes cisplatin resistance through transcriptional regulation of DNA repair pathway, providing rationale for combining CD47-targeted therapies with conventional chemotherapy. This dual approach could simultaneously overcome immune evasion while enhancing treatment efficacy.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2024126
Transcription factor 3 (TCF3), a pivotal member of the TCF/LEF family, plays a critical role in tumorigenesis. Nonetheless, its impact on the tumor microenvironment (TME) and cancer phenotypes remains elusive. We perform an exhaustive analysis of TCF3 expression, DNA variation profiles, prognostic implications, and associations with the TME and immunological aspects. This study is based on a large-scale pan-cancer cohort, encompassing over 17,000 cancer patients from multiple independent datasets, validated by in vitro assays. Our results show that TCF3/4/7 exhibits differential expression patterns between normal and tumor tissues across pan-cancer analyses. Mutational analysis of TCF3 across diverse cancer types reveals the highest alteration rates in biliary tract cancer. Additionally, mutations and single nucleotide variants in TCF3/4/7 are found to exert varied effects on patient prognosis. Importantly, TCF3 emerges as a robust predictor of survival across all cancer cohorts and among patients receiving immune checkpoint inhibitors. Elevated TCF3 expression is correlated with more aggressive cancer subtypes, as validated by immunohistochemistry and diverse cohort data. Furthermore, TCF3 expression is positively correlated with intratumoral heterogeneity and angiogenesis. In vitro investigations demonstrate that TCF3 is involved in epithelial-mesenchymal transition, migration, invasion, and angiogenesis. These effects are likely mediated through the interaction of TCF3 with the NF-κB/MMP2 pathway, which is modulated by IL-17A in human uveal melanoma MUM2B cells. This study elucidates, for the first time, the significant associations of TCF3 with DNA variation profiles, prognostic outcomes, and the TME in multiple cancer contexts. TCF3 holds promise as a molecular marker for diagnosis and as a potential target for novel therapeutic strategies, particularly in uveal melanoma.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025115
This study develops a cell-free protein synthesis (CFPS) system based on the endogenous alcohol oxidase 1 promoter in Komagataella phaffii. The system avoids the dependence of the T7 promoter, thus eliminating the cost issues associated with the T7 RNA polymerase-dependent system in traditional CFPS systems. By integrating an alcohol oxidase 1 promoter-driven GFP expression cassette with optimized K. phaffii cell extract, key components are optimized via a one-factor-at-a-time experiment and a deterministic screening design. This study demonstrates that potassium glutamate and magnesium glutamate have a significant synergistic effect on this system. After optimization, the system achieves a GFP yield of 596.0 mg/L, providing a new record for GFP expression in K. phaffii CFPS systems. This work provides an important theoretical foundation for the further development of T7-independent K. phaffii CFPS systems and their potential applications in scalable bioproduction.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2024241
Circular RNAs (circRNAs) have emerged as a large class of stable and conserved RNAs that are derived primarily from back-splicing of pre-mRNAs and expressed in a cell- and tissue-specific fashion. Recent studies have indicated that a subset of circRNAs may undergo translation through cap-independent pathways mediated by internal ribosome entry sites (IRESs), m6A modifications, or IRES-like short elements. Considering the stability and low immunogenicity of circRNAs, in vitro transcribed circRNAs hold great promise in biomedical applications. In this review, we briefly discuss the noncoding and coding functions of circRNAs in cells, as well as the methods for the in vitro synthesis of circRNAs and current advances in the applications of circRNAs in biomedicine.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2024189
Osteoarthritis (OA) is a significant contributor to pain and disability worldwide. Pain is the main complaint of OA patients attending the clinic and has a large impact on their quality of life and economic standards. However, existing treatments for OA-related pain have not been shown to achieve good relief. The main focus is on preventing and slowing the progression of OA so that the problem of OA pain can be resolved. Pain caused by OA is complex, with the nature, location, duration, and intensity of pain changing as the disease progresses. Previous research has highlighted the role of various forms of cell death, such as apoptosis and necrosis, in the progression of pain in OA. Emerging studies have identified additional forms of novel cell death, such as pyroptosis, ferroptosis, and necroptosis that are linked to pain in OA. Different types of cell death contribute to tissue damage in OA by impacting inflammatory responses, reactive oxygen species (ROS) production, and calcium ion levels, ultimately leading to the development of pain. Evidence suggests that targeting novel types of cell death could help alleviate pain in OA patients. This review delves into the complex mechanisms of OA pain, explores the relationship between different modes of novel cell death and pain, and proposes novel cell death as a viable strategy for the treatment of these conditions, with the goal of providing scientific references for the development of future OA pain treatments and drugs.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024132
Through genome-wide association studies (GWAS) and integrated expression quantitative trait locus (eQTL) analyses, numerous susceptibility genes (“eGenes”, whose expressions are significantly associated with common variants) associated with systemic lupus erythematosus (SLE) have been identified. Notably, a subset of these eGenes is correlated with disease activity. However, the precise mechanisms through which these genes contribute to the initiation and progression of the disease remain to be fully elucidated. In this investigation, we initially identify SPATS2L as an SLE eGene correlated with disease activity. eSignaling and transcriptomic analyses suggest its involvement in the type I interferon (IFN) pathway. We observe a significant increase in SPATS2L expression following type I IFN stimulation, and the expression levels are dependent on both the concentration and duration of stimulation. Furthermore, through dual-luciferase reporter assays, western blot analysis, and imaging flow cytometry, we confirm that SPATS2L positively modulates the type I IFN pathway, acting as a positive feedback regulator. Notably, siRNA-mediated intervention targeting SPATS2L, an interferon-inducible gene, in peripheral blood mononuclear cells (PBMCs) from patients with SLE reverses the activation of the interferon pathway. In conclusion, our research highlights the pivotal role of SPATS2L as a positive-feedback regulatory molecule within the type I IFN pathway. Our findings suggest that SPATS2L plays a critical role in the onset and progression of SLE and may serve as a promising target for disease activity assessment and intervention strategies.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024043
Non-small cell lung cancer (NSCLC) is one of the most prevalent cancers in the world, and early diagnosis can effectively improve patient survival. Here, differentially expressed circIARS genes are screened from the sequencing results, and their molecular characteristics are examined by Sanger sequencing, RNase R assay, agarose gel electrophoresis (AGE), and fluorescence in situ hybridization (FISH). Real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) is performed to detect the expression level of circIARS. The diagnostic value of the signature is analyzed using a subject operating characteristic (ROC) curve. Moreover, plasma is collected from postsurgical, chemotherapy, and relapse patients to investigate the prognostic value of circIARS in NSCLC. The expression of circIARS is greater in both the plasma and tissues of NSCLC patients than in those of healthy individuals, and could be used to distinguish NSCLC patients from patients with benign pulmonary disease (BPD), small cell lung cancer (SCLC) patients, and healthy individuals. The expression level of circIARS relatively decreases after antitumor therapy, such as chemotherapy, and relatively increases after recurrence. ROC analysis reveals that circIARS has better detection efficiency than traditional markers. In addition, circIARS expression level is strongly correlated with several clinicopathological parameters. Finally, we tentatively predict the downstream miRNAs or RBP that might bind to circIARS. Plasma circIARS is significantly greater in NSCLC patients and has good stability and specificity as a diagnostic marker, which could aid in the adjuvant diagnosis and dynamic monitoring of NSCLC.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024121
Gene regulation refers to the precise regulation of gene expression in an organism, and transcription factors are proteins that bind to DNA and regulate gene expression by promoting or inhibiting the expressions of target genes. Since the late 1980s [1], scientists have studied special genes called Pax genes that control how genes function in organisms as they grow. There are nine Pax genes found in animals such as mice, zebrafish, and humans [2]. Based on the composition domain and homology of the sequence, the Pax family is divided into four subfamilies: Pax1/9, Pax2/5/8, Pax4/6, and Pax3/7 [3]. Pax7 plays a pivotal role in the implementation, protection, and repair of skeletal muscle. Pax7 helps to control the balance between self-renewal and differentiation of satellite cells, ensuring that they can proliferate when needed to generate new muscle cells and differentiate into mature muscle fibers when necessary for muscle development and repair. The expression of the Pax7 gene in nerve cells is critical for dorsal root and sensory ganglia development. The Pax7 gene serves as a primary controlling factor for skeletal muscle development while influencing different biological processes; however, its exact role in jawless vertebrates such as lamprey remains unclear, and extensive research is needed to elucidate the intricate underlying mechanisms involved. Given the unique status of lamprey as an ancient jawless fish, possessing an ancient lineage and distinctive biological features, it is rare to explore gene function across hundreds of millions of years of vertebrate evolution. The use of lamprey as a model system for gene function research represents an innovative approach in the fields of evolutionary and comparative genomics. In this study, we investigated the regulatory mechanism of Pax7 in lamprey via gene cloning, gene expression analysis, gene silencing and transcriptome data analysis. We also explored the interactions between genes with significant differences. Identification of Lr.Pax7 in lamprey tissues began with the retrieval of protein sequences that are similar to those of human Pax family members in sea lamprey (Petromyzon marinus) or zebrafish (Danio rerio) from the NCBI protein database (Supplementary Table S1) and the use of BLAST to identify corresponding homologs (Supplementary Table S2). Subsequently, we extracted the Pax sequences from our library. Lethenteron reissneri specimens were dissected to isolate various tissues. Primers targeting the pax domains were designed based on the Pax7 nucleotide sequence in the Lampreys cDNA library, and the aim was to verify the effectiveness of the Lampreys cDNA as a template for validation (Supplementary Table S3). Lr.Pax7 was successfully amplified via PCR in muscle tissue. Here, a variety of methods were used for bioinformatics analysis. The results showed that the amino acid sequence of Pax7 is highly similar among animals (Figure 1A), with a decreasing trend from higher to lower organisms, as revealed by sequence alignment. It can be observed from the evolutionary tree (Figure 1B) that Pax genes for each subfamily are present in ancestral chordate and that Pax genes are present in amphioxus. Petromyzon marinus, Lethenteron camtschaticum, and Lethenteron reissneri constitute a sister group and have become good models for the study of jawless vertebrates. Pax9, Pax2, Pax6, and Pax7 show high similarity to those of other higher vertebrates. Therefore, these genes were named Lr.Pax9, Lr.Pax2, Lr.Pax7, and Lr.Pax6. The results indicate that the Pax7 gene is significantly preserved across various species, from higher to lower. This suggests that the DNA sequence of the gene is remarkably similar among different species. Lr.Pax7 is positioned between vertebrates and invertebrates and is most closely related to P. marinus Pax7. This finding provides more insight into the original evolutionary position of the lamprey. Crystal structure prediction analysis revealed that Lr.Paxs and Hm.Paxs have highly homologous structures (Figure 1C). The Pax gene has a similar structure (Figure 1D), including a conserved DNA-binding structure called the pair-box domain. This structure contains approximately 128 amino acids and is responsible for binding with specific DNA sequences, regulating gene expression, and interacting with other proteins. To further investigate the evolutionary history of Pax7 in vertebrates, we compared the genetic environment of Pax7 with that of other vertebrates (Figure 1E). In addition, many Pax gene members also contain DNA-binding structures called homeodomains, which play important roles in development.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2024203
Increased glycolytic metabolism is a key step in the reproduction of Brucella and the induction of brucellosis, however, little is known about how this process is regulated during infection. Forkhead box protein O1 (FOXO1) is a transcription factor that regulates energy metabolism. In this study, we employ the yeast two-hybrid system (Y2H) and immunoprecipitation (Co-IP) to reverse screen for the FOXO1 for the first time and identify interactions between FOXO1 and the Brucella secretory protein VceA. Our findings reveal that the Brucella secretory protein VceA colocalizes with FOXO1 in the cytoplasm. Additionally, we observe that infection of macrophages with Brucella abortus 2308 (S2308) promotes FOXO1 entry into the nucleus, leading to a significant upregulation of glycolysis level in macrophage. Conversely, in a VceA mutant strain (S2308-ΔVceA), we note a significant reduction in the ability of FOXO1 to enter the nucleus, accompanied by a decrease in glycolysis level. Furthermore, Brucella interacts with FOXO1 through the secreted protein VceA, promoting the entry of FOXO1 into the nucleus and thereby altering host metabolic patterns. This study provides insights into the mechanisms by which Brucella invades host macrophages and induces unique metabolic changes. These insights may offer a novel rationale for developing metabolic therapeutic strategies for the treatment and prevention of related diseases.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2024156
In this study, we aim to investigate diacylglycerol kinase (DGK) γ expression in developing neural tubes (NTs) and its effects on neural stem cell (NSC) proliferation and migration. Whole-mount in situ hybridization (WMISH) and immunohistochemistry are performed to explore DGKγ localization in developing NTs in vivo. NSCs are treated with sh-DGKγ, R59949, or PMA in vitro. Cell counting kit-8 (CCK-8) assay, 5-ethynyl-2′-deoxyuridine (EdU) assay and neurosphere formation assay are utilized to evaluate NSC proliferation. Neurosphere migration assay and a trans-well chamber assay are used to assess NSC migration. The diacylglycerol (DAG) content is detected via enzyme-linked immunosorbent assay (ELISA). The mRNA expression of DGKγ is detected via quantitative real-time polymerase chain reaction (qRT-PCR). The protein expression levels of DGKγ, protein kinase C (PKC) and phosphorylated PKC (p-PKC) are detected via western blot analysis. The results show that DGKγ mRNA is expressed predominantly in developing NTs. The neuroepithelium in developing NTs is positive for NSC markers, including Nestin, glial fibrillary acidic protein (GFAP), and DGKγ. DGKγ is expressed in the cytoplasm and nucleus of the neuroepithelium and is coexpressed with p-PKCγ and p-PKCδ. The proliferation of NSCs, the number of EdU-positive NSCs, and the number of neurospheres are decreased by sh-DGKγ and R59949 but increased by PMA. There is a shorter migration distance of NSCs and fewer migrated NSCs in the sh-DGKγ, R59949 and PMA groups. DAG content and the p-PKCδ/PKCδ ratio are increased by sh-DGKγ, R59949 and PMA, whereas the p-PKCγ/PKCγ ratio is decreased by PMA. Taken together, our findings indicate that DGKγ facilitates NSC proliferation and migration, which is responsible for the participation of DGK in NT development. DGKγ facilitates NSC migration via the DAG/PKCδ pathway.
Chinese Traditional and Herbal Drugs•2026•DOI: 10.7501/j.issn.0253-2670.2026.16.20261624
The bHLH transcription factor family in Forsythia suspensa was systematically identified and characterized using genomic data, yielding 170 members with complete HLH conserved domains distributed across 14 chromosomes. Protein lengths ranged from 67 to 885 amino acids, with relative molecular masses of 7,910.58 to 98,854.78 and theoretical isoelectric points of 4.71 to 10.44. Phylogenetic analysis classified these factors into 13 subfamilies, with subfamily III being the largest. Cis-acting element analysis revealed multiple light-, hormone-, and stress-responsive elements. Exogenous methyl jasmonate (MeJA) treatment of F. suspensa leaves followed by qRT-PCR within 48 h and correlation with phillygenin content identified FsbHLH26 and FsbHLH139 as likely key regulators of phillygenin biosynthesis and accumulation. These findings provide a foundation for elucidating the molecular mechanisms underlying phillygenin biosynthesis.
Chinese Traditional and Herbal Drugs•2026•DOI: 10.7501/j.issn.0253-2670.2026.16.20261603
The inflorescences of Inula japonica Thunb. (Asteraceae) are a traditional Chinese medicine used for treating cough, phlegm, and vomiting. Sesquiterpenoid dimers, formed via Diels-Alder, hetero-Diels-Alder, [2+2] cycloaddition, or radical coupling, exhibit potent anti-inflammatory, neuroprotective, and antitumor activities. However, their low natural abundance and structural complexity hinder isolation and development. This study isolated six sesquiterpenoid dimers from the ethyl acetate fraction of a 90% ethanol extract of I. japonica using multiple chromatographic techniques. Their structures were elucidated by HRESIMS, NMR, IR, UV, and calculated NMR/ECD. Compounds 1 (inujaponolide T) and 3 (inujaponolide U) are new: a eudesmane-guaiane dimer and a 1,10-seco-eudesmane-guaiane dimer, respectively. The other four were identified as inujaponolide E (2), inujaponolide D (4), inujaponolide I (5), and japonicone X (6). In vitro anti-hepatocellular carcinoma activity was evaluated against HepG2 cells using MTT and colony formation assays. All compounds exhibited potent cytotoxicity with IC50 values of 2.61–13.94 μmol/L; compound 6 was most active (IC50 = 2.61 μmol/L). A preliminary structure-activity relationship indicated a positive correlation between the number of acetoxy substituents and antitumor activity. Compounds 1 and 3 inhibited cell viability and reduced colony formation in a dose-dependent manner. These findings expand the chemical diversity of I. japonica and provide a basis for developing these dimers as anti-hepatocellular carcinoma lead compounds.
Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-026-05095-1
Background: Human umbilical cord mesenchymal stem cells (UC-MSCs) are promising for cellular therapy due to their accessibility, low ethical concerns, and immunomodulatory and tissue repair capacities. However, heterogeneity during in vitro expansion poses quality control challenges. Methods: Two fetal umbilical cords were obtained; primary UC-MSCs were isolated and passaged continuously. Cells were harvested for single-cell RNA sequencing; 78,178 cells and 14 subpopulations were analyzed. Validation used in vitro assays and in vivo studies. Results: Mid-passage UC-MSCs showed superior functional performance based on differential gene expression and functional enrichment. An optimal subpopulation (C8) was identified by holistic evaluation of stemness, hematopoietic support, and immunomodulation. NOTCH signaling was enriched in C8, with NOTCH2 as the dominant receptor. MLPH and LPXN were identified as signature markers; MLPHhighLPXNhigh UC-MSCs displayed higher hematopoietic support and immunosuppression than MLPHlowLPXNlow cells. Conclusions: Mid-passage UC-MSCs are favorable for clinical use. The subpopulation with high NOTCH activity exhibits enhanced hematopoietic support and immunosuppression. MLPH and LPXN are ideal markers for isolating this functional subpopulation.
Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-026-04991-w
Type 2 diabetes (T2D) and its complications involve multiple pathophysiological processes. Conventional therapies partially regulate blood glucose but fail to reverse disease progression or prevent complications. This review summarizes current research advances and challenges of using mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) for treating T2D and its complications. It introduces MSC-EV characteristics, then analyzes mechanisms and therapeutic prospects of natural MSC-EVs, focusing on inflammatory modulation, tissue regeneration, and improving insulin resistance. Engineering strategies—optimizing MSC culture conditions, modifying EV contents, and establishing MSC-EV delivery systems based on bioactive materials—are discussed to boost EV yield and quality while enhancing therapeutic efficacy. Current challenges include limited yield and high heterogeneity of natural MSC-EVs, long-term safety, immunocompatibility, and large-scale production of engineered MSC-EVs. The review emphasizes artificial intelligence in guiding future research directions. These summaries are crucial for clinical translation of MSC-EVs and will ultimately provide T2D patients with an effective and safe treatment option.
Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-026-04913-w
Extracorporeal cardiac shock wave (ECSW) therapy has been shown to enhance endothelial colony-forming cell (ECFC) function, but its potential as a preconditioning strategy for myocardial infarction (MI) therapy remains undefined. This study evaluated the efficacy and mechanism of intravenously delivered ECSW-preconditioned ECFCs (SW-ECFCs) in a rat MI model. ECFCs were isolated from ApoE-/- rat bone marrow and characterized. RNA sequencing revealed significant enrichment of the PI3K/AKT pathway in SW-ECFCs. In vitro assays demonstrated that ECSW enhanced ECFC migration, tube formation, proliferation, and VEGF-A secretion while reducing apoptosis; these effects were interrogated using the PI3K/AKT inhibitor LY294002. An acute MI model was established via left anterior descending coronary artery ligation in ApoE-/- rats, randomized into four groups: MI + PBS, MI + ECFCs, MI + SW-ECFCs, and MI + LY294002-pretreated SW-ECFCs (LY-SW-ECFCs), with sham controls. Comprehensive evaluations included echocardiography, serum injury biomarkers, TTC staining, histopathology (H&E, Masson), immunohistochemistry for cardiomyocyte apoptosis and p-eNOS, immunofluorescence for ECFC homing and vascular markers (CD31, α-SMA, VEGF-A), nitric oxide measurement, and Western blot analysis of PI3K/AKT signaling proteins. Results confirmed that ECSW preconditioning significantly improved cardiac function and structural repair, mediated primarily through PI3K/AKT pathway activation, augmenting cell homing, paracrine activity, and survival. This work presents a novel and promising strategy for cardiac regeneration.
Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-026-05044-y
Tooth loss remains a major unmet clinical challenge, and current prosthetic approaches cannot restore the biological complexity, sensory function, or regenerative capacity of natural teeth. Recent progress in stem cell biology, developmental engineering, and regenerative biomaterials has opened new possibilities for biological tooth regeneration. This review integrates advances across three major research domains that together define the current landscape of translational regenerative dentistry. First, we discuss stem cell-based, scaffold-guided strategies for tooth regeneration. These approaches combine dental and nondental stem cells, including DPSCs, SCAPs, PDLSCs, SHED, and iPSC-derived lineages, with bioactive materials such as HA/TCP ceramics, dentin-derived extracellular matrix scaffolds, and natural or synthetic polymers to promote odontogenic differentiation, vascularization, and periodontal attachment. Second, we summarize emerging tooth organoid and bioengineered tooth germ technologies that recapitulate epithelial–mesenchymal interactions and enable controlled reconstruction of dentin–pulp and periodontal compartments for modeling human odontogenesis. Third, we highlight molecular regulation-driven therapeutic strategies, focusing on the modulation of Wnt, BMP, FGF, TGF-β, and USAG-1 pathways to stimulate endogenous tooth regeneration and correct developmental defects. Despite marked progress, challenges remain, including stable neurovascular integration, optimization of stem cell–material crosstalk, precise control of spatiotemporal signaling, and long-term functional stability in vivo. Finally, we outline future directions involving smart biomaterials, gene- and protein-based molecular targeting, organoid-guided regeneration, and iPSC-enabled personalized therapies, which may further accelerate the clinical translation of stem cell-based tooth regeneration.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025148
Mesothelial cells play an important role in colorectal cancer peritoneal metastasis (CRC-PM), where they support tumor growth and invasion. In this study, we investigate the molecular mechanisms by which mesothelial cells contribute to CRC metastasis. Using single-cell RNA sequencing (scRNA-seq) on tissue samples from 12 CRC patients with peritoneal metastasis, we identify PDK4 as a key gene in mesothelial cells during metastasis. The expression of PDK4 is significantly greater in mesothelial cells undergoing mesothelial-to-mesenchymal transition (MMT) compared to normal peritoneal cells, suggesting its involvement in mesothelial cell reprogramming during peritoneal metastasis. In vitro experiments show that coculturing mesothelial cells with CRC cells leads to increased PDK4 expression, which in turn enhances mesothelial cell migration and invasion. Knockdown of PDK4 reduces mesothelial cell invasion, while overexpression of PDK4 increases invasive ability, highlighting its critical role in mesothelial cell invasion. Additionally, PDK4 promotes metabolic changes, specifically increasing fatty acid oxidation (FAO), which is necessary for mesothelial cell invasion. Blocking FAO reduces the invasive ability of PDK4-overexpressing mesothelial cells, while restoring FAO in PDK4-knockdown cells rescues their invasion potential. Further analysis shows that PDK4 enhances the acetylation of β-catenin, a protein involved in cell movement, and that this modification is crucial for mesothelial cell invasion. Our results suggest that PDK4 regulates mesothelial cell invasion through β-catenin acetylation following metabolic reprogramming, offering a potential target for therapies aimed at inhibiting CRC-PM.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2026030
The recombination-activating gene (RAG)-mediated V(D)J rearrangement is essential for adaptive immunity in jawed vertebrates. RAG evolved from an invertebrate RAG-like (RAGL) transposase, with the amphioxus protoRAG (BbRAG1L/BbRAG2L) serving as a key model. However, the regulatory mechanisms of protoRAG remain unclear. Here, we developed an in vitro proximity labeling assay using TurboID fused to BbRAG1L or BbRAG2L to identify interacting proteins from amphioxus hepatic cecum and colon lysates. The fusion proteins were expressed in Expi293F cells, purified, and incubated with amphioxus lysates in the presence of biotin and ATP. Biotinylated proteins were enriched via streptavidin beads and analyzed by LC-MS/MS. This approach enables the identification of protoRAG-interacting proteins without the need for transgenic amphioxus, providing a valuable tool to study the evolution of RAG regulation.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2026081
Multiple myeloma (MM) patients frequently experience relapse, disease progression, and drug resistance, necessitating novel therapeutic strategies. This study investigates the role of peptidylprolyl isomerase A (PPIA) in mediating dihydroartemisinin (DHA)-induced ferroptosis in MM. Building on our previous work establishing the prognostic relevance of ferroptosis in MM, we elucidate the mechanism by which DHA triggers this form of cell death through the disruption of iron metabolism and redox homeostasis. DHA significantly reduces the viability of MM cell lines and primary CD138+ cells derived from patient bone marrow samples and attenuates tumor burden in orthotopic MM models. Mechanistically, DHA upregulates the iron-regulatory genes transferrin receptor 1 (TFRC) and heme oxygenase-1 (HMOX1), thereby perturbing iron homeostasis and promoting ferroptosis. Crucially, DHA targets the oxidized form of PPIA, a redox-sensitive chaperone, binding to it and preventing its reduction, which elevates intracellular reactive oxygen species (ROS). Combined treatment with DHA and erastin, which concurrently disrupt iron and amino acid metabolism, exerts synergistic cytotoxicity and enhances MM inhibition. Furthermore, in a syngeneic mouse model, DHA promotes T-cell activation and augments tumor suppression. Collectively, these findings underscore PPIA's pivotal role in a novel ferroptotic cell death pathway and reveal new therapeutic opportunities for MM.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2026074
Tryptophan (Trp)-substituted antimicrobial peptides (AMPs) exhibit enhanced interactions with bacterial cell membranes, potentially improving their antimicrobial efficacy. Klebsiella pneumoniae (20.59% of 2054 ICU isolates) is resistant to multiple clinically used antibiotics and presents significant treatment challenges. In the present study, three Trp-modified peptides (I4W, L12W, and I1WL5W) are generated by substituting Ile or Leu residues in temporin-1CEb, a peptide derived from frog skin, with Trp at various sites to assess their antibacterial effects and mechanisms against K. pneumoniae. Compared with L12W, both I4W and I1WL5W display superior antimicrobial activity and lower cytotoxicity. Mechanistic studies reveal that AMPs exert antibacterial and bactericidal effects through bacterial surface charge neutralization, insertion into bacterial cell membranes, increase permeability of both the inner and outer membranes, and disruption of membrane integrity. Notably, I1WL5W exhibit the most potent membrane-disrupting activity. Assessment of the impact of Trp-containing peptides on bacterial biofilms reveals that these peptides not only inhibit exopolysaccharide production and biofilm formation but also degrade preformed biofilms. A murine lung infection model is established to investigate the therapeutic efficacy of I1WL5W against MDRKP 1203-induced lung infection in mice. Compared with the control treatment, treatment with I1WL5W results in reduced bacterial counts and levels of IL-6 and TNF-α in both the blood and lung tissues of MDRKP 1203-infected mice, and treatment with I1WL5W improves lung tissue structure. The present study provides valuable insights for designing Trp-containing peptides with potent antimicrobial properties by facilitating their penetration across bacterial membranes.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21205
BACKGROUND: Macrophage polarization demonstrates significant potential in disease treatment, particularly in areas such as cancer, inflammation, and autoimmune diseases. Establishing standardized in vitro models can lay the groundwork for in-depth research into the mechanisms of macrophage polarization. OBJECTIVE: To observe the in vitro growth characteristics of bone marrow-derived macrophages from C57BL/6 mice and to establish a standardized in vitro model for M1 and M2 macrophage polarization. METHODS: Femurs and tibias of C57BL/6 mice were aseptically separated, and the contents of the bone marrow cavity were collected. After filtering through a mesh and lysing erythrocytes, the contents were resuspended in high-glucose DMEM containing 20 ng/mL macrophage colony-stimulating factor and inoculated in 6-well plates according to experimental requirements. On day 7, they were differentiated into mature mouse bone marrow-derived macrophages (M0 type). Then, 100 ng/mL lipopolysaccharide was used to induce polarization to M1 type, and 20 ng/mL interleukin-4 was used to induce polarization to M2 type. Flow cytometry and RT-qPCR were used to detect the expression of corresponding markers in macrophages under different polarization states, and Western blot was used to detect the expression of M1 macrophage marker pathway proteins p-STAT1, STAT1 and M2 macrophage marker pathway proteins p-STAT6, STAT6. RESULTS AND CONCLUSION: (1) After stimulation with 20 ng/mL macrophage colony-stimulating factor for 7 days, flow cytometry showed that the positive rate of macrophage surface marker F4/80 reached 98.1%. (2) After stimulation with 100 ng/mL lipopolysaccharide for 6 h, the positive rates of F4/80 and CD86 were about 35%, and RT-qPCR showed that the mRNA expression of M1 macrophage markers inducible nitric oxide synthase, interleukin-6, macrophage inflammatory protein 1α, and monocyte chemoattractant protein 1 were significantly higher than those in the control group (P < 0.01). (3) After stimulation with 20 ng/mL interleukin-4 for 24 h, the mean fluorescence intensity of CD206 was significantly increased, and RT-qPCR showed that the mRNA expression of M2 macrophage markers Chi3l3 (Ym1), interleukin-10, and arginase 1 were significantly higher than those in the control group (P < 0.01). (4) Western blot results showed that lipopolysaccharide-induced M1 macrophage marker pathway protein p-STAT1 was significantly activated; interleukin-4-induced M2 macrophage marker pathway protein p-STAT6 was significantly activated. These results indicate that lipopolysaccharide and interleukin-4 effectively induced polarization of bone marrow-derived macrophages to M1 and M2 types, respectively.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21286
BACKGROUND: Yougui Pill is derived from Jingyue Quanshu. Studies have confirmed that Yougui Pill is highly effective in treating patients with knee osteoarthritis, but its mechanism of action remains unclear. OBJECTIVE: To explore the potential molecular mechanism of Yougui Pill in improving knee osteoarthritis in rats. METHODS: Forty-eight SPF-grade Sprague-Dawley rats were randomly divided into four groups: blank control group, model group, Yougui Pill group and celecoxib group. The latter three groups were subjected to modified Hulth method for surgical modeling of knee osteoarthritis. After wound healing, rats were driven for 8 weeks. After modeling, the celecoxib group was given celecoxib suspension by gavage, the Yougui Pill group was given Yougui Pill decoction by gavage, and the sham operation group and model group were given equal volume of normal saline, once daily for 4 weeks. Hematoxylin-eosin staining, toluidine blue staining, and safranin O-fast green staining were used to observe the pathological changes of rat cartilage tissue; transmission electron microscopy was used to observe the ultrastructure of rat chondrocytes; ELISA was used to detect the levels of interleukin-18, interleukin-1β, and tumor necrosis factor-α in rat serum; western blot was used to detect the protein expression of PI3K, AKT, NF-κB, p-PI3K, p-AKT, p-P65, NLRP3, GSDMD, GSDMD-N, Caspase1, Cleaved-Caspase1, interleukin-18, and interleukin-1β in rat cartilage tissue. RESULTS AND CONCLUSION: Compared with the blank group, the model group showed severe destruction of cartilage edge, cartilage tissue defect, thinning and disordered arrangement of cartilage layer cells, subchondral bone hyperplasia, disordered tide line, severe structural damage of chondrocytes, formation of pyroptotic bodies, significantly increased serum levels of tumor necrosis factor-α, interleukin-18, and interleukin-1β (P < 0.05), and significantly increased protein expression of p-PI3K, p-AKT, p-P65, NLRP3, GSDMD-N, Cleaved-Caspase1, interleukin-18, and interleukin-1β in cartilage tissue (P < 0.01). Compared with the model group, the cartilage structure of rats in the Yougui Pill group and celecoxib group tended to be normal, with deeper cartilage staining, thicker cartilage, more complete chondrocyte membrane, significantly decreased serum levels of tumor necrosis factor-α, interleukin-18, and interleukin-1β (P < 0.05), and significantly decreased protein expression of p-PI3K, p-AKT, p-P65, NLRP3, GSDMD-N, Cleaved-Caspase1, interleukin-18, and interleukin-1β in cartilage tissue (P < 0.01). Compared with the celecoxib group, the Yougui Pill group showed more regular arrangement of chondrocytes, smoother articular cartilage surface, significantly thickened cartilage layer, relatively complete tide line, relatively complete chondrocyte membrane, significantly decreased serum levels of tumor necrosis factor-α, interleukin-18, and interleukin-1β (P < 0.05), and significantly decreased protein expression of p-PI3K, p-AKT, p-P65, NLRP3, GSDMD-N, Cleaved-Caspase1, interleukin-18, and interleukin-1β in cartilage tissue (P < 0.01). These results indicate that Yougui Pill can improve the inflammatory response of chondrocytes in rats with knee osteoarthritis, and the mechanism may be related to inhibiting the activation of PI3K/AKT/NF-κB pathway, thereby regulating NLRP3/Caspase1/GSDMD pathway-mediated pyroptosis.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21299
BACKGROUND: Neurogenic heterotopic ossification frequently occurs within 1 to 3 months following spinal cord injury or traumatic brain injury, characterized by abnormal bone formation in periarticular soft tissues. The precise pathogenesis remains unclear, underscoring the urgent need for systematic research to inform clinical management. OBJECTIVE: To summarize recent advances in animal models of neurogenic heterotopic ossification and elucidate its underlying mechanisms, with a particular focus on the pathological differentiation of osteogenic precursor cells, remodeling of the local tissue microenvironment, and the interplay between neural regulation and neurogenic heterotopic ossification formation. METHODS: PubMed, CNKI, and SinoMed were searched from inception to January 2025. Chinese search terms included 'neurogenic heterotopic ossification, spinal cord injury, traumatic brain injury, heterotopic ossification'; English search terms included 'Neurogenic Heterotopic Ossification, spinal cord injury, Traumatic brain injury, ossification, heterotopic, Central nervous system'. Literature related to animal models and mechanisms of neurogenic heterotopic ossification was included to summarize key pathogenic processes. RESULTS AND CONCLUSION: The recruitment and aberrant osteogenic differentiation of osteogenic precursor cells (mainly fibro-adipogenic progenitors) are regulated by local microenvironmental factors such as hypoxia, inflammation, and angiogenesis. Neurotrophic factors, calcitonin gene-related peptide, and substance P promote aberrant ossification through neuro-immune interactions. Future research should construct a systematic molecular map, explore core signaling pathways, and develop novel targeted interventions to achieve early identification and individualized treatment of neurogenic heterotopic ossification, thereby improving patient outcomes.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21291
BACKGROUND: ABL1 is involved in the regulation of multiple cellular processes, yet its functions within the cardiovascular system remains largely unexplored. In particular, its role in cardiac ischemia/reperfusion injury and necroptosis has not been reported. OBJECTIVE: To investigate the role of ABL1 in cardiac ischemia/reperfusion injury and myocardial necroptosis, as well as the underlying molecular mechanisms. METHODS: (1) Animal experiment: C57BL/6J mice were randomly divided into four groups: sham surgery group, ischemia/reperfusion group, ABL1 knockdown + ischemia/reperfusion group, and ABL1 negative control + ischemia/reperfusion group. Lentiviral vectors targeting ABL1 were injected in situ into the myocardium. One week later, ischemia/reperfusion injury was induced by ligation of the left anterior descending coronary artery followed by reperfusion. ABL1 protein expression, cardiac function, myocardial fibrosis, and cardiomyocyte surface area were assessed. (2) Cell experiment: H9c2 cells were divided into four groups: negative control cell line + PBS, ABL1 knockdown cell line + PBS, negative control cell line + H2O2 500 µmol/L, and ABL1 knockdown cell line + H2O2 500 µmol/L. Additionally, H9c2 cells were divided into five groups: negative control cell line + PBS, negative control cell line + H2O2 500 µmol/L, ABL1 knockdown cell line + H2O2 500 µmol/L, ABL1 knockdown cell line + Parkin overexpression adenovirus + H2O2 500 µmol/L, and ABL1 knockdown cell line + Parkin negative control adenovirus + H2O2 500 µmol/L. Cell viability, necroptosis, reactive oxygen species levels, and mitochondrial membrane potential were measured. Expression of ABL1, Parkin, and cyclophilin D was detected, and the interaction between ABL1 and Parkin was examined. RESULTS AND CONCLUSION: (1) ABL1 protein expression was significantly downregulated in the mouse cardiac ischemia/reperfusion model. (2) Knockdown of ABL1 exacerbated ischemia/reperfusion-induced cardiac dysfunction, as evidenced by decreased left ventricular ejection fraction and fractional shortening, and increased left ventricular end-systolic and end-diastolic diameters. (3) Knockdown of ABL1 promoted ischemia/reperfusion-induced myocardial fibrosis and aggravated ventricular remodeling. (4) ABL1 protein expression was significantly downregulated in the cardiomyocyte oxidative stress model. (5) Knockdown of ABL1 exacerbated oxidative stress-induced cell viability loss, necroptosis, and reactive oxygen species accumulation. (6) ABL1 regulated mitochondrial membrane permeability, modulated the expression of Parkin and cyclophilin D, and regulated cellular oxidative stress levels by targeting Parkin. (7) These results indicate that ABL1 expression is significantly downregulated in both in vivo ischemia/reperfusion and in vitro oxidative stress models, and knockdown of ABL1 aggravates cardiac ischemia/reperfusion injury and cardiomyocyte oxidative stress injury, acting through the Parkin-CypD pathway.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21428
OBJECTIVE: In recent years, many scholars have applied 3D-printed artificial vertebrae to anterior cervical vertebral subtotal vertebral resection and bone grafting fusion, but whether it is more effective than traditional titanium cages remains controversial. This study aims to systematically evaluate the effectiveness and safety of 3D-printed artificial vertebrae compared with traditional titanium cages as implants for anterior cervical corpectomy and fusion in the treatment of spondylosis. METHODS: Databases such as CNKI, WangFang, CBM, VIP, PubMed, EMBASE, and The Cochrane Library were searched to collect the clinical research on the application of 3D-printed artificial vertebrae in anterior cervical corpectomy and fusion from the establishment of each database to February 2025. After screening the literature, extracting the data and evaluating the methodological quality of the included studies, the meta-analysis was performed using Rev Man 5.4 software. RESULTS: A total of 10 studies were included, comprising 2 prospective randomized controlled studies, 6 retrospective cohort studies, and 2 prospective cohort studies, all of high quality. The included studies involved 534 patients, with 273 in the 3D-printed group and 261 in the control group. Meta-analysis results showed that the 3D-printed group was superior to the control group in terms of operation time [SMD=-1.13, 95%CI(-1.87, -0.39), P=0.003], loss of intervertebral disc height at last follow-up [SMD=-3.01, 95%CI(-5.74, -0.29), P=0.03], neck disability index at 3 months postoperatively [SMD=-0.34, 95%CI(-0.66, -0.03), P=0.03], prosthesis subsidence rate [OR=0.19, 95%CI(0.11, 0.32), P < 0.000 01], and postoperative dysphagia incidence [OR=0.43, 95%CI(0.21, 0.90), P=0.03], with significant differences. There were no significant differences in blood loss, hospital stay, postoperative Japanese Orthopaedic Association score, postoperative visual analogue scale score, postoperative neck disability index (at 6 months and last follow-up), and fusion rate between the two groups (P > 0.05). CONCLUSION: Compared with traditional titanium cages, 3D-printed artificial vertebral bodies have significant advantages in improving surgical efficiency, maintaining postoperative intervertebral disc height, reducing postoperative dysphagia incidence, and reducing prosthesis subsidence rate.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21416
BACKGROUND: Non-infectious poor wound healing following lumbar surgery is a significant clinical complication that prolongs hospitalization and increases the risk of reoperation. However, its predictive indicators remain unclear. Based on the hypothesis that paraspinal muscle degeneration may impede tissue repair by altering the local microenvironment, this study aimed to investigate the predictive value of preoperative paraspinal muscle fatty infiltration for non-infectious poor wound healing and its association with osteoporosis. OBJECTIVE: To quantify the degree of paraspinal muscle fatty infiltration using preoperative MRI and evaluate its predictive value for non-infectious poor wound healing after lumbar surgery. METHODS: A retrospective analysis was conducted on medical records of 4,368 patients who underwent traditional open posterior lumbar surgery at Third Affiliated Hospital of Guangzhou University of Chinese Medicine between 2019 and 2024. We screened 190 patients with a postoperative hospital stay of 15 days or longer. Based on postoperative wound healing and infection indicators, 41 patients with non-infectious poor healing were selected as the poor healing group. From the remaining 4,178 patients, 40 patients with good healing were selected as the good healing group. The poor healing group was further subdivided into osteoporosis and non-osteoporosis subgroups. Preoperative lumbar MRI images were collected, and Image J software was used to measure the cross-sectional area of the psoas major muscle and the percentage of fat infiltration in the erector spinae and multifidus muscles. RESULTS AND CONCLUSION: (1) There were no significant differences in gender, age, or diabetes between the poor healing and good healing groups (P > 0.05). (2) The functional cross-sectional area and fat infiltration percentage of the psoas major, erector spinae, and multifidus muscles were significantly different between the two groups (P < 0.05). (3) Logistic regression analysis showed that fat infiltration percentage was an independent risk factor for poor wound healing. (4) Receiver operating characteristic curve analysis showed that fat infiltration percentage had high predictive value for poor wound healing (area under the curve > 0.7). (5) One-way ANOVA indicated that osteoporosis was a risk factor for fat infiltration in the L4 multifidus muscle (P < 0.05). (6) The results indicate that paraspinal muscle fat infiltration percentage is an important predictor of non-infectious poor wound healing after traditional open posterior lumbar surgery, providing clinical reference. Osteoporosis was also confirmed as a risk factor for L4 multifidus fat infiltration, but due to the small subgroup sample size, whether osteoporosis affects non-infectious poor healing after lumbar surgery requires further clinical trials.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21424
BACKGROUND: A combination of subjective and objective evaluation criteria is often required to more accurately and comprehensively assess knee function in patients undergoing anterior cruciate ligament reconstruction. OBJECTIVE: To review the evolving trends in effectiveness and safety evaluation criteria after anterior cruciate ligament reconstruction and analyze the dynamic shift in the use of subjective and objective assessment tools. METHODS: A systematic search of PubMed and Embase was conducted up to August 22, 2023 to identify studies assessing knee function after anterior cruciate ligament reconstruction. A total of 136 eligible studies meeting the inclusion criteria were included. The frequency of each evaluation standard was extracted and analyzed over time using Origin 2025 software. RESULTS AND CONCLUSION: (1) Between 1990 and 2005, objective measures were widely applied. Since 2005, subjective scoring systems, particularly patient-reported outcome measures, have increased sharply, surpassing objective standards in frequency from 2009 onward. (2) Early use was dominated by the Lysholm scale and Tegner activity score, while the International Knee Documentation Committee-Subjective Knee Form, Knee Injury and Osteoarthritis Outcome Score, and anterior cruciate ligament–return to sport after injury gradually emerged as the main tools in later years. (3) In contrast, objective assessments such as the KT1000/2000 arthrometer, Lachman test, and hop test remained relatively stable but showed an overall declining trend. (4) These findings indicate a paradigm shift from objective knee stability to patient-centered subjective experience in evaluating ACL reconstruction outcomes. (5) This study is the first to quantitatively reveal the dynamic evolution of mainstream evaluation tools, highlighting the current emphasis on combining subjective and objective criteria. The recommended combination is the International Knee Documentation Committee-Subjective Knee Form or Knee Injury and Osteoarthritis Outcome Score plus anterior cruciate ligament–return to sport after injury plus KT1000/2000 or hop test, to comprehensively reflect knee function recovery and patient perception, providing an evidence base for future comprehensive assessment approaches.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21405
BACKGROUND: Vancomycin is widely used as a first-line drug for treating methicillin-resistant Staphylococcus aureus infections in orthopedic perioperative infection prevention and treatment. However, its narrow therapeutic window and large individual differences make blood drug concentration monitoring crucial for ensuring efficacy and safety. OBJECTIVE: To establish the ultra-performance liquid chromatography-tandem mass spectrometry method to determine the concentration of vancomycin in plasma, and explore the correlation of blood drug concentration changes with clinical efficacy and acute renal impairment. METHODS: Totally 200 orthopedic patients with bone infection who were hospitalized in Beijing Jishuitan Hospital Guizhou Hospital from January 2020 to May 2022 were selected. Blood drug concentration was measured by ultra-performance liquid chromatography-tandem mass spectrometry. Renal function indexes (blood creatinine and urea nitrogen) were monitored, and the clinical efficacy and acute renal impairment were analyzed in patients with different vancomycin blood concentration levels. RESULTS AND CONCLUSION: (1) The established UPLC-MS/MS method had a linear range of 0.5-120.0 μg/mL (R²=0.997), intra-day relative standard deviation of 4.82%-6.57%, inter-day relative standard deviation of 10.2%-12.3%, and accuracy of 97.3%-106%. (2) The clinical effective rate in the 10-20 μg/mL group (82%) was significantly higher than that in the <10 μg/mL group (67%) (P < 0.05). (3) The incidence of renal impairment in the >20 μg/mL group (35.0%) was significantly higher than that in the 10-20 μg/mL group (16.0%) and <10 μg/mL group (6.7%) (P < 0.05). (4) The established UPLC-MS/MS method is sensitive and accurate, and can be used for clinical monitoring of vancomycin blood concentration. Maintaining vancomycin blood concentration within 10-20 μg/mL can achieve the best clinical efficacy and reduce the risk of nephrotoxicity. Blood concentration monitoring is of great significance for guiding individualized administration.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21368
BACKGROUND: In the process of applying artificial intelligence to orthopedic imaging, the technical system exhibits a clear hierarchical structure: machine learning is the primary pathway to achieving artificial intelligence, while convolutional neural networks, a branch of deep learning, have become the core model for image analysis. Clarifying this technical lineage helps to systematically review the research evolution and trends in this field through bibliometric methods. OBJECTIVE: To comprehensively analyze the research status and development trends of artificial intelligence in the field of orthopedic imaging based on bibliometric methods, providing ideas and methods for future research. METHODS: By searching the Web of Science Core Collection database, with keywords including artificial intelligence, deep learning, convolutional neural network, and orthopedic imaging, a total of 460 relevant English articles published between 2015 and 2025 were included. CiteSpace 6.4.R1, VOSviewer 1.6.20, and Bibliometrix software were used to conduct visual analysis from dimensions such as annual publication volume, country and institution distribution, author collaboration network, keyword co-occurrence, clustering, and burst word evolution. RESULTS AND CONCLUSION: (1) The number of publications in this field has steadily increased over the past 10 years. (2) China and the United States are the main publishing countries, with the United States showing outstanding performance in citation frequency and international collaboration influence; Sichuan University, the University of California, and Harvard University constitute a core collaborative institutional network. (3) Research hotspots mainly focus on bone age assessment, automated image segmentation, and the application of deep learning in fracture detection and osteoarthritis diagnosis. Related keywords such as bone age assessment, automated segmentation, and deep learning have continued to burst, indicating the evolutionary trajectory of research focus. (4) The research enthusiasm for artificial intelligence in orthopedic imaging continues to rise, with intelligent segmentation, disease grading, and multimodal data fusion being important future research directions. (5) This paper systematically reviews the field from a macro perspective, providing a reference for promoting the deep integration of artificial intelligence technology in orthopedic clinical practice; through bibliometric analysis, it constructs a knowledge map of the application of artificial intelligence in orthopedic imaging, systematically summarizes the research status and hotspots in this field, and aims to provide reference and guidance for future related research.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21346
BACKGROUND: Cell transplantation is one of the effective approaches for repairing spinal cord injury. Our research team previously found that transplanted cerebrospinal fluid-contacting neurons can survive and promote motor function recovery in mice with spinal cord injury. However, whether these transplanted cerebrospinal fluid-contacting neurons differentiate into functional neurons and thereby facilitate motor function recovery remains unclear. OBJECTIVE: To investigate whether transplanted cerebrospinal fluid-contacting neurons differentiate into functional neurons in vivo and contribute to motor function recovery after spinal cord injury. METHODS: Primary cells containing cerebrospinal fluid-contacting neurons were isolated from the cervical spinal cord of C57BL/6 neonatal mice within 24 hours of birth and cultured adherently. Cells were transduced with a lentivirus carrying a multimodal imaging gene, and cerebrospinal fluid-contacting neurons were selected and purified using puromycin. Differentiation was induced with serum-containing differentiation medium, and expression of neuronal marker NeuN and motor neuron marker ChAT was detected by immunofluorescence. Thirty C57BL/6 mice were randomly divided into three groups: transplantation group and PBS group underwent T10 spinal cord injury by clip compression, while sham group only had laminectomy. One week after injury, cerebrospinal fluid-contacting neurons were transplanted in situ in the transplantation group, and an equal volume of PBS was injected in the PBS group. At 1, 4, and 8 weeks after transplantation, immunofluorescence was used to detect expression of motor neuron marker ChAT in spinal cord tissue. At 8 weeks, immunofluorescence was used to detect synaptic marker SYN, inhibitory transmitter marker GAD65/67, and excitatory transmitter marker vGLUT1; hematoxylin-eosin staining was used to observe spinal cord morphology; BMS motor function score and footprint analysis were used to assess motor function recovery. RESULTS AND CONCLUSION: (1) Cerebrospinal fluid-contacting neurons expressed neural stem cell characteristics in vitro and could differentiate into motor neurons. (2) Transplanted cerebrospinal fluid-contacting neurons could survive long-term in vivo and differentiate into motor neurons. (3) The proportion of cerebrospinal fluid-contacting neurons differentiating into motor neurons was highest at 8 weeks (P < 0.0001). (4) At 8 weeks after transplantation, cerebrospinal fluid-contacting neurons co-expressed SYN, GAD65/67, and vGLUT1, indicating synaptic connections with host neurons. (5) BMS scores of PBS group were consistently lower than those of transplantation group (P < 0.001); footprint analysis showed more coordinated gait in transplantation group with only toe dragging, while PBS group showed obvious hindlimb dragging. (6) Hematoxylin-eosin staining showed large cavities in the injured area of PBS group, while cavities were reduced in transplantation group. These results indicate that transplanted cerebrospinal fluid-contacting neurons can differentiate into motor neurons both in vitro and in vivo, form synaptic connections, and thereby improve motor function in spinal cord-injured mice.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21434
BACKGROUND: Existing pharmacological treatments for gout are frequently limited by substantial side effects, underscoring the urgent need to discover novel therapeutic targets and develop more targeted drugs. OBJECTIVE: To identify genetic targets for gout, and to predict promising therapeutic compounds as well as traditional Chinese medicines by integrating druggable gene datasets with Mendelian randomization and colocalization analysis approaches. This work will lay a foundation for in-depth exploration of the pathogenesis of gout in the Chinese population, and provide insights for the clinical management and development of new targeted drugs. METHODS: Gout-related datasets were obtained from the Finnish database FinnGen R11. Blood expression quantitative trait loci data were obtained from the GWAS catalog website developed by the MRC Integrative Epidemiology Unit at the University of Bristol. Mendelian randomization analysis was performed to identify potential targets; colocalization analysis was used to identify key susceptibility genes for gout. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were used to explore gene functions, and protein-protein interaction networks were used to screen closely interacting targets. The Drug-Gene Interaction Database developed by Washington University School of Medicine in St. Louis was used to predict compounds with potential therapeutic effects. Molecular docking was used to predict the binding degree of compounds to core targets. The Coremine Medical database founded by PubGene was used to predict traditional Chinese medicines related to core genes. All databases used are public resources. A gout cell model was established using monosodium urate crystal-induced RAW264.7 cells to preliminarily verify the expression of key genes and the intervention effect of compounds. CCK-8 assay and cell invasion assay were used to screen safe doses and optimal administration concentrations. ELISA was used to measure inflammatory factor levels, and real-time fluorescence quantitative reverse transcription PCR was used to detect mRNA expression of key targets and pathways. RESULTS AND CONCLUSION: (1) Mendelian randomization analysis identified 40 potential gene targets significantly associated with gout; colocalization analysis identified Jun proto-oncogene as a key susceptibility gene for gout; protein-protein interaction network showed that Jun proto-oncogene, mitogen-activated protein kinase 3, and 3-hydroxy-3-methylglutaryl-CoA reductase had close interactions. (2) Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment results showed that potential targets mainly regulate mitogen-activated protein kinase, tumor necrosis factor, ErbB, interleukin-17, hypoxia-inducible factor 1, Toll-like receptor and other signaling pathways, and intervene in positive regulation of extracellular signal-regulated kinase 1/2 cascade, glutathione metabolism, ubiquitin protein regulation and other processes. (3) Based on potential targets, 372 compounds with potential intervention effects were predicted, including capsaicin, 5,6-benzoflavone, L-glutamic acid, quercetin, honokiol, kaempferol, cinnamaldehyde, and andrographolide. (4) Molecular docking showed that capsaicin and 5,6-benzoflavone had high binding affinity with core targets such as Jun proto-oncogene. (5) 79 potential targeted traditional Chinese medicines were predicted, including Atractylodes, Magnolia officinalis, Smilax glabra, Alisma orientale, and Salvia miltiorrhiza, with efficacy mainly concentrated in clearing heat and detoxifying, promoting blood circulation and removing blood stasis, and resolving phlegm and dampness. (6) In cell experiments, CCK-8 and cell invasion assay results showed that the optimal safe dose of capsaicin was 50 μmol/L. In the model group, the expression of key gene Jun proto-oncogene was significantly upregulated, and capsaicin could significantly downregulate the mRNA expression of Jun proto-oncogene and mitogen-activated protein kinase pathway-related genes such as c-Jun N-terminal kinase, extracellular signal-regulated kinase 1/2, and p38, and reduce the levels of interleukin-6, interleukin-1β, and tumor necrosis factor α in cell supernatant. (7) Data mining results suggest that compounds such as capsaicin and 5,6-benzoflavone and traditional Chinese medicines such as Atractylodes and Smilax glabra may exert therapeutic effects on gout by intervening in targets such as Jun proto-oncogene and mitogen-activated protein kinase 3, regulating tumor necrosis factor, Th-17, hypoxia-inducible factor 1 and other pathways, and mitogen-activated protein kinase cascade, protein ubiquitination, and glutathione metabolism. Among them, the key susceptibility gene JUN can serve as a potential diagnostic marker for gout. Treatment methods mainly focusing on clearing heat and detoxifying combined with promoting blood circulation and removing blood stasis can be key to gout treatment. (8) Cell experiments preliminarily verified the expression of JUN gene and mitogen-activated protein kinase pathway in gout cell model and the intervention effect of capsaicin, providing a basis and foundation for the next step of gout diagnosis and treatment targets and new drug development.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21435
BACKGROUND: Studies have suggested that palmitoylation-mediated regulation offers distinct advantages in osteoarthritis. Therefore, it is essential to utilize whole-genome data to explore novel key drug-targetable tissue-constructing hubs of palmitoylation regulation in osteoarthritis from a genetic perspective. OBJECTIVE: To explore novel key drug targets involved in palmitoylation-mediated regulation of osteoarthritis pathogenesis through Mendelian randomization analysis, thereby providing valuable insights for developing targeted therapeutic strategies against osteoarthritis. METHODS: We identified 31 palmitylation-related genes from three independent studies and cross-referenced them with 15 695 druggable genes from the eQTLGen Consortium database (which is publicly available and aims to better understand diseases at the plasma proteome gene level, containing multiple druggable gene targets). This yielded 22 potential palmitoylation drug targets. Using drug-target Mendelian randomization, sensitivity analysis, and colocalization analysis, we identified novel drug targets for palmitoylation-regulated osteoarthritis (from GWAS Catalog database, established by the National Human Genome Research Institute, summarizing data from published genome-wide association studies). GeneMANIA and STRING interaction network analyses were performed to explore potential interacting proteins of the novel drug target. After further validation with osteoarthritis validation genes (also from GWAS Catalog), we determined the interacting proteins of the novel drug target. RESULTS AND CONCLUSION: (1) After matching 31 palmitoylation genes, 22 potential palmitoylation drug targets were obtained. Through Mendelian randomization, sensitivity analysis, and colocalization analysis, zinc finger DHHC-type containing 2 (ZDHHC2) was identified as a novel drug target for palmitoylation-regulated osteoarthritis. GeneMANIA and STRING analyses revealed 7 potential interacting proteins, and validation with osteoarthritis genes suggested a strong interaction between ZDHHC3 and ZDHHC2. These results indicate that ZDHHC2 is a novel key drug target in palmitoylation-regulated osteoarthritis pathogenesis, and ZDHHC3, as an interacting protein, may exert synergistic effects, facilitating future construction of efficient and safe drug prevention and treatment chains for osteoarthritis patients through palmitoylation regulation. (2) The use of international databases and European populations provides important reference for Chinese biomedical and clinical research, offering clues for osteoarthritis research in the Chinese population from a genetic perspective. This approach can also be used to screen drug gene targets in Chinese populations, target palmitoylation regulation, and promote personalized and precise medication for osteoarthritis prevention and treatment.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21469
BACKGROUND: Currently, three-dimensional (3D) bioprinting technology, with its controllable multi-scale structure and functional integration design capabilities, has become a cutting-edge solution for tendon tissue engineering. OBJECTIVE: To systematically summarize the latest research progress of 3D bioprinting technology in tendon repair. METHODS: Using the keywords “3D printing, bioink, myotendinous junction, tendon repair, tendon-bone junction, bionic scaffold,” literature searches were conducted in the PubMed and Web of Science databases, as well as in the China National Knowledge Infrastructure (CNKI) with the same keywords. Articles with weak relevance to the topic were excluded, and 109 articles were ultimately included for review. RESULTS AND CONCLUSION: 3D bioprinting technology, through multi-material integration and controllable biomimetic structural design, effectively reproduces the multi-level structure of tendons. Mainstream technologies (such as melt electrowriting, extrusion-based printing, etc.) play differentiated advantages in fiber alignment, interface simulation, and dynamic regulation, constructing mechanical transition layers at the muscle-tendon interface and four-zone gradient structures at the tendon-bone interface. Functionalized bioink innovations (immunomodulatory materials, cross-species oxygen-supplying scaffolds, etc.) and multi-technology synergy (aligned fiber deposition + photocuring reinforcement) enhance scaffold bioactivity and mechanical-biological coupling. In the full healing cycle (support in the inflammatory phase, guidance in the proliferative phase, regulation in the remodeling phase), precise intervention from molecular to macroscopic levels is achieved, optimizing collagen alignment and repair mechanical properties. Differentiated repair strategies (multi-material gradients, aligned fibers, gradient scaffolds) for the muscle-tendon interface, tendon body, and tendon-bone interface have made progress. Despite challenges such as resolution-efficiency contradictions and insufficient material matching, 3D printing technology still provides new strategies for tendon repair from structural biomimicry to functional regeneration. In the future, the integration of intelligent materials (photothermal/piezoelectric) and multimodal technologies (4D printing, organoids) is expected to promote dynamic functional regeneration and provide technical references for interface repair.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21453
BACKGROUND: Three-dimensional bioprinted hydrogels have become an important research direction for the repair of oral tissue defects. Pre-vascularization of hydrogels can be achieved by loading endothelial cells and stromal cells. However, the dense hydrogel fibers often limit cell viability and extension. Whether increasing the internal porosity of the hydrogel can improve pre-vascularization remains unclear. OBJECTIVE: To construct porous three-dimensional bioprinted hydrogels loaded with human umbilical vein endothelial cells and human dental pulp stem cells, and to explore the relationship between hydrogel pore size and pre-vascularization. METHODS: (1) Methacrylate gelatin solution and poly (ethylene oxide) solution were mixed at volume ratios of 2:1, 1:1, 1:1.5, 1:2, and 1:3, with pure methacrylate gelatin solution as a control. Three-dimensional bioprinting was performed, and after curing and crosslinking, poly (ethylene oxide) was leached out to form pores. Based on porosity measurements, the mixed solutions with methacrylate gelatin solution and poly (ethylene oxide) solution volume ratios of 1:1, 1:2, and 1:3, and pure methacrylate gelatin solution were selected for subsequent experiments. (2) The above four solutions were used as bioinks to encapsulate human umbilical vein endothelial cells or human dental pulp stem cells for three-dimensional bioprinting. After curing and crosslinking, poly (ethylene oxide) was leached out to form pores. Live/dead staining was used to detect cell viability. Both cells were co-encapsulated for three-dimensional bioprinting, and after curing and crosslinking, poly (ethylene oxide) was leached out to form pores. Tube formation assay was used to detect vascular network formation. (3) The four groups of three-dimensional bioprinted hydrogels with or without encapsulated cells were implanted subcutaneously into CB17-SCID mice. After 14 days, samples were harvested, and hematoxylin-eosin and CD31 immunohistochemical staining were used to observe vascular formation within the hydrogels. RESULTS AND CONCLUSION: (1) The pure methacrylate gelatin group had the smallest pores. As the proportion of poly (ethylene oxide) solution in the bioink increased, the pore size of the hydrogels increased. The 2:1 group had too small pores, and the 1:2 and 1:1.5 groups had similar pore sizes; therefore, the 2:1 and 1:1.5 groups were excluded from subsequent experiments. (2) Live/dead staining showed that human umbilical vein endothelial cells in the four groups did not spread significantly, while human dental pulp stem cells in the 1:2 and 1:3 groups spread significantly. There was no significant difference in cell viability of human umbilical vein endothelial cells or human dental pulp stem cells cultured for 3 days among the groups. The pure methacrylate gelatin group had the least vascular formation, and as the proportion of poly (ethylene oxide) solution increased, vascular formation in the three-dimensional bioprinted hydrogels increased, with denser network structures. (3) Hematoxylin-eosin and CD31 immunohistochemical staining showed no vascular formation in hydrogels without cells, and no vascular formation in the pure methacrylate gelatin group and the 1:1 group with cells, while obvious vascular formation was observed in the other two groups. (4) These results indicate that the internal pores of three-dimensional bioprinted methacrylate gelatin hydrogels can promote the formation of vascular-like structures in vitro by human umbilical vein endothelial cells and human dental pulp stem cells, and promote in vivo vascularization of the hydrogels.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21492
BACKGROUND: Previous studies from our group have shown that triptolide exerts protective effects on nerve cells and alleviates symptoms of neurodegenerative diseases. However, whether it acts by improving mitochondrial dynamic abnormalities requires further investigation. OBJECTIVE: To explore the effect and mechanism of triptolide in regulating the mitochondrial fusion-fission balance to mitigate hydrogen peroxide (H₂O₂)-induced apoptosis in SH-SY5Y cells. METHODS: Human neuroblastoma SH-SY5Y cells were cultured and divided into three groups: control group, model group (200 μmol/L H₂O₂), and triptolide group (2.5 nmol/L triptolide + 200 μmol/L H₂O₂). After 24 hours of intervention, oxidative stress markers (superoxide dismutase activity and malondialdehyde levels), mitochondrial membrane potential, and apoptosis levels were measured. Western blot was used to detect the expression of apoptosis-related proteins, mitochondrial dynamics-related proteins, and respiratory chain-related proteins. Immunofluorescence staining was used to detect the expression of phosphorylated dynamin-related protein 1, optic atrophy protein 1, cytochrome C oxidase 1, and ATP synthase F1 subunit alpha. RESULTS AND CONCLUSION: Compared with the control group, the model group showed significantly decreased superoxide dismutase activity, mitochondrial membrane potential, anti-apoptotic protein Bcl-2, mitochondrial fusion proteins 1 and 2, optic atrophy protein 1, and oxidative phosphorylation complex proteins (NADH dehydrogenase [ubiquinone] iron-sulfur protein 8, ubiquinol-cytochrome c reductase core protein 2, cytochrome c oxidase 1, succinate dehydrogenase B, ATP synthase F1 subunit alpha) (P < 0.05). Meanwhile, malondialdehyde levels, pro-apoptotic proteins Bax and Caspase-3, mitochondrial fission protein 1, phosphorylated dynamin-related protein 1 expression, and apoptosis rate were significantly increased (P < 0.05). Compared with the model group, triptolide intervention reduced malondialdehyde levels, increased superoxide dismutase activity and mitochondrial membrane potential, promoted fusion protein expression, inhibited fission protein expression, increased oxidative phosphorylation complex protein levels, and decreased apoptosis rate (P < 0.05). These results confirm that triptolide can regulate mitochondrial dynamic imbalance to alleviate H₂O₂-induced apoptosis in SH-SY5Y cells.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21488
BACKGROUND: Mangiferin, a major bioactive compound derived from mango trees, is widely present in various traditional Chinese medicinal herbs and exhibits multiple biological functions including antibacterial, cholesterol-lowering, and anti-allergic effects. Existing studies have suggested that mangiferin may prevent and treat osteoarthritis pain. However, its specific mechanism of action remains unclear to date. OBJECTIVE: To systematically investigate the key targets and potential mechanisms of mangiferin in the treatment of osteoarthritis by integrating gene expression omnibus (GEO) microarray data analysis, network pharmacology, and molecular docking techniques, and to validate the findings in a rat model. METHODS: First, GEO microarray data were mined to identify potential therapeutic targets for osteoarthritis. Next, professional databases were integrated to predict the targets of mangiferin, and target information related to osteoarthritis was collected. A Venn diagram was generated using the Weishengxin platform, a protein-protein interaction network was constructed based on the STRING database, and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed. Cytoscape 3.8.0 software was used to construct a drug-target-pathway-disease network, and molecular docking analysis and visualization were performed using the CBDOCK2 online docking platform. A rat model of osteoarthritis was established by anterior cruciate ligament transection of the left knee joint, and different concentrations of mangiferin were administered to observe and record the therapeutic effects. RESULTS AND CONCLUSION: A total of 144 potential targets of mangiferin were identified from multiple databases. Protein-protein interaction network analysis revealed important targets including interleukin-6, tumor necrosis factor, and nuclear factor kappa B1. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis showed that 235 signaling pathways might be involved, including lipid and atherosclerosis-related pathways, advanced glycation end products-receptor, hypoxia-inducible factor 1, and estrogen, which are closely related to inflammation. In animal experiments, after 4 weeks of intervention with 40 μmol/L mangiferin, there was no significant difference in hindlimb weight-bearing compared with the sham-operated group. These findings suggest that mangiferin may exert therapeutic effects on osteoarthritis through a multi-target, multi-pathway mode of action, providing a new strategy and theoretical support for the treatment of osteoarthritis.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21604
BACKGROUND: Polyetheretherketone (PEEK) synthetic material has become one of the preferred materials for repairing skull defects due to its low density, high strength, good toughness, excellent processing performance, and good biocompatibility, but there are few bibliometric analyses of PEEK for skull repair. OBJECTIVE: To explore the overall research trends, development context, research focuses, and hotspots of PEEK materials in the field of international skull defect repair using bibliometric methods. METHODS: The Web of Science Core Collection database was systematically searched for literature on PEEK materials for skull defect repair published from 1995 to 2024. On this basis, bibliometric methods were used to conduct quantitative statistics and visual analysis from the aspects of temporal dynamics of publication volume, country/region contribution, core research institution cooperation network, highly cited papers, high-yield journals, and keyword co-occurrence. RESULTS AND CONCLUSION: This study analyzed 105 studies on PEEK for skull defect repair published from 2009 to 2024. The development process was roughly divided into three stages: 2009-2014 traditional materials, 2015-2019 clinical research on PEEK, and 2020-2024 3D printing and finite element analysis, with the 2020-2024 stage accounting for 42%. Meanwhile, "3D printing, finite element analysis" and "PEEK, titanium alloy" were high-frequency technology combinations. China (21 articles), the United States (17 articles), and Germany (12 articles) were the main research countries. PEEK has been used in more than 200,000 clinical applications worldwide, with an infection rate of 3.7%, lower than that of polymethyl methacrylate (9.2%). PEEK research has shifted from "passive repair" to "active bioactivity promotion". Europe and the United States lead in clinical translation of 3D printing (equipment rate 82%, while China's domestic rate is 39%), but there is a lag of about 2 years between literature and clinical application for 3D-printed PEEK. It is predicted that conductive PEEK will accelerate translation in 2026-2027. The results indicate that PEEK has achieved a transformation from "passive repair" to "active bioactivity promotion", with 3D printing, surface modification, and intelligent integration as core directions. Global PEEK development is uneven; underdeveloped regions have high demand but less research (12%). China focuses on clinical research (68%) but lacks basic innovation (15%). It is necessary to promote low-cost 3D printing technology, establish translation hubs, support interdisciplinary research teams, and build a 10-year multicenter follow-up system.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21520
BACKGROUND: 10-Hydroxy-2-decenoic acid (10-HDA) exhibits potent anti-inflammatory, antioxidant, and immunomodulatory effects, but its role in regulating bone metabolism remains unclear. OBJECTIVE: To investigate the regulatory effects and potential mechanisms of 10-HDA in bone remodeling. METHODS: Rat bone marrow mesenchymal stem cells (BMSCs) were cultured with different concentrations of 10-HDA (0, 0.5, 1, 2, 4 mmol/L); cytoskeletal staining, live/dead staining, and CCK-8 assay were used to assess cell morphology, viability, and proliferation. For osteogenic differentiation, BMSCs were cultured with 10-HDA (0, 0.5, 1, 2 mmol/L) and osteogenic induction; alkaline phosphatase (ALP) and alizarin red staining were performed, and osteogenic-related protein expression was analyzed by western blot and immunofluorescence. Mouse bone marrow mononuclear cells were induced to differentiate into macrophages and cultured in osteoclast differentiation medium with different concentrations of 10-HDA (0, 0.5, 1, 2 mmol/L); tartrate-resistant acid phosphatase (TRAP) and F-actin staining were used to detect osteoclast formation. BMSCs were serum-starved for 6 h and then cultured normally, divided into control, 10-HDA, 10-HDA+AS1842856 (FOXO1 inhibitor), and 10-HDA+EX-527 (SIRT1 inhibitor) groups; 10-HDA concentration was 0.5 mmol/L. Western blot and immunofluorescence were used to analyze SIRT1/FOXO1 pathway activation and expression of autophagy- and osteogenesis-related proteins. BMSCs were divided into control, H2O2, and H2O2+10-HDA groups; 10-HDA concentration was 0.5 mmol/L; after H2O2 treatment for 24 h, corresponding drug interventions were applied; after osteogenic induction, ALP and alizarin red staining were performed. BMSCs were divided into five groups: control, H2O2, H2O2+10-HDA, H2O2+10-HDA+AS1842856, and H2O2+10-HDA+EX-527; 10-HDA concentration was 0.5 mmol/L; after H2O2 treatment for 24 h, corresponding drug interventions were applied; western blot was used to detect SIRT1/FOXO1 signaling pathway and antioxidant-related protein expression; TUNEL and β-galactosidase staining were used to assess apoptosis and senescence. RESULTS AND CONCLUSION: Cytoskeletal staining, live/dead staining, and CCK-8 assay showed that 0.5, 1, 2 mmol/L 10-HDA promoted proliferation of rat BMSCs; these three concentrations were selected for subsequent experiments. ALP, alizarin red staining, western blot, and immunofluorescence analysis showed that 0.5 mmol/L 10-HDA promoted osteogenic differentiation and mineralization of rat BMSCs and increased osteogenic-related protein expression. TRAP and F-actin staining showed that 0.5 mmol/L 10-HDA significantly inhibited osteoclast formation. Western blot and immunofluorescence showed that 10-HDA activated the SIRT1/FOXO1 signaling pathway, promoted FOXO1 deacetylation and nuclear translocation, and upregulated autophagy-related proteins and antioxidant enzymes. ALP and alizarin red staining showed that under oxidative stress, 10-HDA promoted osteogenic differentiation and mineralization of rat BMSCs. Western blot showed that under oxidative stress, 10-HDA enhanced the antioxidant capacity of rat BMSCs by activating the SIRT1/FOXO1 signaling pathway. TUNEL and β-galactosidase staining showed that under oxidative stress, 10-HDA reduced apoptosis and senescence of rat BMSCs via activation of the SIRT1/FOXO1 signaling pathway. These findings indicate that 10-HDA enhances autophagy and antioxidant capacity through regulation of the SIRT1/FOXO1 signaling pathway, thereby promoting osteogenic differentiation.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21150
BACKGROUND: Breast hyperplasia is a common benign breast disease mainly caused by endocrine disorders, manifested as abnormal hyperplasia of breast tissue. In recent years, traditional Chinese medicine compounds and probiotics have shown good potential in regulating the endocrine system and improving the intestinal microecology, providing new ideas for the treatment of breast hyperplasia. OBJECTIVE: To explore the effects and mechanisms of traditional Chinese medicine compounds and fermented probiotic compounds on breast hyperplasia in mice, providing new theoretical and experimental bases for the clinical treatment and prevention of breast hyperplasia. METHODS: (1) Network pharmacology tools were used to predict the anti-breast-hyperplasia activity of Herba Gueldenstaedtiae (Euphorbia humifusa), as well as its potential targets and signaling pathways. The databases included: TCMSP, OMIM, GeneCards database, UniProt website, Venny2.1.0 website, Metascape, HERB website, and STRING database, all of which are open-access databases. Network pharmacology can predict and screen key information such as the targets corresponding to the active ingredients of traditional Chinese medicine, disease targets, and action pathways through network analysis and computer-system analysis. Therefore, it has been increasingly widely used in the research of traditional Chinese medicine. (2) A breast hyperplasia model was induced in mice by injecting estrogen and progesterone. Mice in the normal blank group were injected intraperitoneally with normal saline every day. Mice in the model group and drug-administration groups were injected intraperitoneally with estradiol benzoate injection at a concentration of 0.5 mg/kg every day for 25 days. From the 26th day, the injection of estradiol benzoate injection was stopped. Mice in the normal blank group were injected intramuscularly with normal saline every day, and mice in the model group and drug-administration groups were injected intramuscularly with progesterone injection at a concentration of 5 mg/kg for 5 days. After the model was established, each group was given drugs respectively. The normal blank group and the model group were gavaged with 0.2 mL/d of normal saline; the positive blank group (Xiaozheng Pill group) was gavaged with an aqueous solution of Xiaozheng Pill at 0.9 mg/g; the low-, medium- and high-dose groups of Compound Herba Gueldenstaedtiae were gavaged with an aqueous solution of the compound medicine at 0.75, 1.5, and 3.0 mg/(g·d) respectively; the low-, medium- and high-dose groups of traditional Chinese medicine-bacteria fermentation were gavaged with an aqueous solution of the compound medicine at 0.75, 1.5, and 3.0 mg/(g·d) respectively. The administration was continuous for 30 days. RESULTS AND CONCLUSION: (1) The results of network pharmacology research showed that the Compound Herba Gueldenstaedtiae (Euphorbia humifusa) contained 46 active ingredients, which were related to 1 213 potential targets. After comparison with 588 known breast-hyperplasia targets, it was speculated that 50 of these targets might be related to the direct effect of the compound on breast hyperplasia. (2) After drug intervention, there was no significant change in the high-dose group of Compound Herba Gueldenstaedtiae compared with the normal blank group. The liver indicators of the other intervention groups all significantly decreased (P < 0.05). (3) In terms of kidney and uterine indicators, the medium-dose group of Compound Herba Gueldenstaedtiae decreased significantly compared with the normal blank group (P < 0.05). In terms of the uterine index, the model group increased significantly compared with the normal blank group (P < 0.01). (4) After 1-month drug treatment, the number of lobules and acini in the breast tissue of the Xiaozheng Pill group, the low, medium, and high-dose group of Compound Herba Gueldenstaedtiae, the low, medium, and high-dose groups of traditional Chinese medicine-bacteria fermentation decreased, and the duct openings narrowed. With the increase of drug dose, diffuse hyperplasia of breast tissue was significantly improved. (5) The ELISA results showed that compared with the model group, the estrogen level was lower in the medium-dose group of traditional Chinese medicine-bacteria fermentation after the intervention (P < 0.05). In addition, the follicle-stimulating hormone level in the low-dose group of Compound Herba Gueldenstaedtiae was lower than that of the model group (P < 0.05). (6) The intervention in the mouse model led to changes in the abundance of short chain fatty acids and intestinal flora in all groups. To conclude, the Compound Herba Gueldenstaedtiae and its probiotic fermentation products significantly improved mammary gland hyperplasia in mice by regulating hormone levels, improving the structure of the gut microbiota, and increasing the content of short-chain fatty acids, providing new ideas and potential sources of drugs for the treatment of breast hyperplasia.
Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-026-04898-6
Background: Bionic treatment strategies for spinal cord injury (SCI) seek to emulate natural morphological structures and regeneration processes. Zebrafish, possessing remarkable regenerative capabilities, were employed to investigate the regulatory pattern of spinal vascular regeneration following SCI, aiming to inform bionic SCI therapy development. Methods: Live imaging monitored zebrafish spinal perineural vessel plexus (PNVP) formation, which occurs at approximately 18 days post-fertilization (dpf). SCI modeling was timed at 19 dpf. Radial glia (RGs) in Tg(gfap:NTR-mCherry) reporter fish were chemically ablated using metronidazole (Mtz) or nitrofuropyrinol (Nfp). Vascular repair patterns, injured area vascular coverage, and endothelial cell (EC) counts were assessed. Vegfaa expression profiles and public single-cell sequencing data (GSE202429) were analyzed to postulate downstream pathways, validated with specific inhibitors. Results: RGs were successfully ablated (>90% efficiency) with 10 mM Mtz or 1.25 µM Nfp. In Mtz/Nfp+SCI groups, vascular coverage and EC numbers were significantly reduced versus DMSO+SCI controls. Vegfaa reporter signal declined notably in the injured region post-ablation. Inhibitor experiments supported involvement of Vegfa-PI3K/Akt-mTOR and Notch signaling pathways. Conclusion: RGs play a pivotal role in spinal vascular regeneration after SCI in zebrafish, likely via Vegfa-PI3K/Akt-mTOR and Notch pathways. Mimicking zebrafish RG pro-regenerative functions may achieve pro-vascular repair in mammals after SCI.
Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-026-05027-z
Retinal organoids (ROs) derived from human pluripotent stem cells are crucial for modeling retinal development and disease. However, the functional electrophysiological maturation of photoreceptors within ROs remains poorly characterized. This study aimed to define the functional maturation timeline of photoreceptors in human embryonic stem cell (hESC)-derived ROs. H9 hESC-derived ROs which included a CRX-tdTomato reporter line for specific photoreceptor identification were utilized. An integrated approach of RNA-sequencing analysis, immunofluorescence staining, and whole-cell patch-clamp recordings was employed to systematically assess photoreceptor maturation over 300 days of differentiation. Transcriptional and protein analysis revealed progressive upregulation of key ion channels. Patch-clamp recordings demonstrated stage-dependent maturation of membrane properties, which stabilized by D120–125. Hyperpolarization-activated cyclic nucleotide-gated (HCN) channel-mediated currents (Ih) increased progressively, peaking at D240, with amplitudes comparable to mature primate photoreceptors. Voltage-gated sodium (Nav) currents also showed significant developmental upregulation, reaching a maximum, stable plateau from D210–215 onward. Pharmacological blockade confirmed the identity of HCN and Nav currents. Critically, the capacity for action potential (AP) generation increased developmentally, with the proportion of photoreceptors capable of firing APs rising from 16.7% at D90–95 to a peak of 90.2% by D240–245. This study defines a comprehensive electrophysiological maturation timeline for photoreceptors in human ROs and establishes D240 as a key benchmark for functional maturity, characterized by peak Ih currents and AP generation capacity equivalent to mature native photoreceptors. These findings provide essential physiological criteria for standardizing RO quality control, enhancing their utility for modeling retinal degenerative diseases and developing cell replacement therapies.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2026078
Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have demonstrated clinical benefits in heart failure with preserved ejection fraction (HFpEF), yet the underlying mechanisms remain poorly defined. Given that mitochondrial dysfunction represents a central feature of HFpEF pathophysiology, we investigate whether modulation of mitochondrial homeostasis contributes to the cardioprotective effects of dapagliflozin. Using a Dahl salt-sensitive rat model of HFpEF, we find that dapagliflozin markedly improves diastolic function and attenuates cardiac hypertrophy, fibrosis, and apoptosis. These beneficial effects are accompanied by significant restoration of mitochondrial structure and function. Consistently, in an in vitro HFpEF model, dapagliflozin enhances mitochondrial respiratory capacity in cardiomyocytes, indicating a direct mitochondrial regulatory effect. Mechanistically, integrative transcriptomic and experimental analyses identify the SIRT1/PGC-1α/Mitofusin-2 (Mfn-2) signaling axis as a critical pathway suppressed in HFpEF but reactivated following dapagliflozin treatment. Activation of this pathway promotes mitochondrial biogenesis and improves mitochondrial dynamics, thereby preserving cardiomyocyte homeostasis. Collectively, our findings reveal that dapagliflozin exerts cardioprotective effects in HFpEF by restoring mitochondrial homeostasis through the SIRT1/PGC-1α/Mfn-2 axis, providing mechanistic insight into SGLT2i-mediated benefits and highlighting mitochondrial regulation as a potential therapeutic strategy for HFpEF.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025181
Colorectal cancer (CRC) is one of the most prevalent and lethal cancers worldwide and is characterized by uncontrolled cell invasion, migration, and proliferation. The progression of CRC is driven by genetic mutations and alterations in key signaling pathways. This study investigates the role of GPSM2 and ZNF263 implicated in CRC progression. The GPSM2 gene, which regulates G protein signaling pathways, plays a vital role in cell movement and growth, contributing to the metastatic potential of cancer cells. The ZNF263 gene, a zinc finger protein involved in gene expression regulation, is also linked to CRC progression, with its dysregulation affecting the cell cycle, apoptosis, and migration. In particular, this study explores how ZNF263 acts as a transcription factor, modulating the expression of GPSM2 to increase CRC cell invasion, migration, and proliferation. This study confirms that ZNF263 activates the cell cycle pathway in a GPSM2-dependent manner, driving the aggressive behavior of CRC cells. Bioinformatics analysis using the GEO database further supports these findings, identifying key genetic alterations in CRC. These insights provide a deeper understanding of the molecular mechanisms underlying CRC progression and highlight the potential of ZNF263 and GPSM2 as therapeutic targets for intervention. This study underscores the importance of early detection and exploration of targeted therapies to improve CRC patient outcomes.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025246
The recombination-activating gene (RAG) complex initiates adaptive immunity by catalyzing V(D)J recombination to generate diverse antigen receptors. While the catalytic function of the RAG core is well defined, its regulatory interactions and physiological roles remain poorly understood due to limited knowledge of RAG-associated proteins. The RAG complex forms a heterotetramer of two RAG1 and RAG2 subunits, yet the individual contributions of each subunit remain unclear. Here, we use TurboID-mediated proximity labelling to map the human RAG interactome. By fusing TurboID to RAG1 or RAG2, we identify 88 RAG1- and 146 RAG2-associated proteins, with only 23 shared proteins, indicating distinct sets of proximal proteins. Although RAG1 and RAG2 are thought to exert their physiological functions by forming a complex, they display distinct potential interaction networks, suggesting subunit-specific functions and revealing their spatial proximity to each subunit. These findings uncover distinct RAG1 and RAG2 interaction landscapes and establish a framework for exploring broader RAG functions in immunity.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025070
Diabetes mellitus (DM) is a metabolic and endocrine disorder with a projected global prevalence of 783 million by 2045. Individuals with type 2 diabetes face a 20–60% elevated risk of cognitive dysfunction, yet therapeutic options remain limited. This study investigates the efficacy of Schisandrin A (SchA), a bioactive lignan from Schisandra chinensis, in a streptozotocin-induced diabetic rat model. Rats were randomized into control, DM, DM+SchA, and Con+SchA groups. SchA treatment improved insulin sensitivity, reduced blood glucose, and significantly attenuated fear memory impairment. Histological analysis revealed decreased prefrontal cortex damage, enhanced synaptic protein expression, and reduced Aβ42 formation. Mechanistically, SchA suppressed microglial activation and inflammatory markers while increasing phosphorylation of insulin resistance pathway proteins. Furthermore, SchA mitigated ferroptosis by upregulating GPX4, SLC7A11, Nrf2, HO-1, and SIRT1 in the diabetic prefrontal cortex. These findings suggest that SchA alleviates diabetes-associated memory impairment by concurrently reducing neuroinflammation and ferroptosis, positioning SchA as a potential therapeutic agent for diabetes-related cognitive decline.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025063
Homologous recombination (HR) is the high-fidelity pathway for repairing DNA double-strand breaks (DSBs) during S/G2 phases, and its dysfunction drives genomic instability and cancer progression. The MRN complex (MRE11/RAD50/NBS1) initiates DNA end resection, a critical step for HR, but how MRE11 recruitment and activity are regulated remains incompletely defined. Here we identify FOXD3 as a novel HR factor that interacts with PARP1 and is recruited to DSB sites in a PARP1-dependent manner. FOXD3 directly binds MRE11 and promotes its recruitment to DSBs, ensuring proper end resection. Depletion of FOXD3 impairs HR-mediated DSB repair, reduces chromosome stability, and sensitizes cancer cells to ionizing radiation. These findings establish FOXD3 as a key regulator of MRE11-mediated end resection and suggest that FOXD3 expression levels could serve as a biomarker for HR proficiency and as a therapeutic target to induce synthetic lethality with PARP inhibitors or radiotherapy. The study provides mechanistic insight into the early steps of HR and highlights the clinical potential of targeting FOXD3 in cancers with HR defects.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025105
Demyelinating diseases of the central nervous system (CNS) are characterized by failed remyelination, largely due to arrested oligodendrocyte precursor cell (OPC) differentiation. This review synthesizes evidence on the crosstalk between oligodendrocytes (OLGs) and other glial cells—astrocytes, microglia, and neurons—in the context of demyelination. OLGs, the myelin-forming cells of the CNS, are essential for axonal integrity and saltatory conduction. Under pathological conditions, factors including astrocyte-derived PDGF and leukemia inhibitory factor (LIF), microglial polarization states, and neuronal activity modulate OLG survival, metabolic support, and process outgrowth. Astrocytes promote process outgrowth via basic fibroblast growth factor (bFGF) and extracellular matrix interactions, while also regulating iron metabolism and exosomal secretion from OPCs through integrin β4-mediated adhesion. Microglial heterogeneity, with M1/M2 polarization, influences neuroinflammation and remyelination outcomes. The review highlights that astrocyte activation via STAT3 signaling determines the balance between oligodendrocyte and Schwann cell remyelination. These intercellular interactions significantly impact myelin regeneration and offer potential therapeutic targets. Modulating these interactions at specific temporal stages may provide novel strategies for treating demyelinating diseases and related neurological conditions. The integration of single-cell resolution data on microglial heterogeneity and spatial-temporal dynamics is critical for developing targeted interventions.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025094
Kainate receptors (KARs), members of the ionotropic glutamate receptor (iGluR) family, are established targets for neurological disorder therapeutics, yet their functional repertoire in jawless vertebrates remains undefined. This study identified four iGluR subunits in lamprey—Lr-GRIA2, Lr-GRIA4, Lr-GRIK1, and Lr-GRIN2B—with phylogenetic placement outside jawed vertebrate clades and conserved N-terminal ECDs. Functional interrogation of Lr-GRIK1 via siRNA silencing (5-, 2.3-, and 2.56-fold reduction at 24, 48, and 96 h post-transfection) followed by transcriptome sequencing revealed 9 genes with |log2 FC| > 1 and P < 0.05, enriched in signal transduction and immune pathways. Upregulated transcripts included MAP3K9, ANKRD1, HMOX2, ANKRD13B, NDKB, ADCY8, PKC, PCLO, NOG1L, and SDK2. Kidney tissue monitoring post-stimulation confirmed Lr-GRIK1 modulates immune-related molecule expression. These data establish a non-neurotransmission role for Lr-GRIK1 in lamprey immunity, demonstrating that KARs negatively regulate immune responses in this basal vertebrate lineage.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025066
Chromosome congression and spindle assembly are essential for genomic stability, and their dysregulation is linked to tumorigenesis. WDR5, a core component of the MLL methyltransferase complex, directly binds Kif2A to regulate mitotic events, but the structural basis of this interaction remained unresolved. Here, the crystal structure of WDR5 in complex with a Kif2A-derived peptide (residues 114–122) was determined at 1.85 Å resolution. Kif2A engages both the WIN and S7 sites of WDR5 via Arg117 and Ser121; Ser121 forms hydrogen bonds with WDR5 Tyr191 and Lys259, inducing Tyr191 rotation and opening the S7 pocket. Structures of WDR5 with truncated or mutated Kif2A peptides and a WDR5 Y191F variant reveal the dynamic nature of Tyr191. Anti-WDR5 compounds exhibit a similar binding mode at the WIN-S7 site. Mutagenesis combined with isothermal titration calorimetry (ITC) assays underscore the critical roles of Arg117 and Ser121 in mediating Kif2A–WDR5 binding. These findings provide atomic-level insights into the non-canonical mitotic function of the MLL/WDR5 complex and highlight WIN-S7 sites as promising therapeutic targets for diseases associated with chromosomal instability, such as cancers.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025201
Colorectal cancer (CRC) remains the third most common malignancy and second leading cause of cancer mortality worldwide, with 608,000 new cases and 202,000 deaths annually in China. The Warburg effect, characterized by elevated glucose consumption and lactate production under normoxia, sustains CRC proliferation, migration, chemoresistance, and stemness. Prior work established that SUN5, a nuclear membrane protein, promotes CRC proliferation and migration, but its role in glycolysis remained undefined. Here, SUN5 overexpression increased glucose uptake and lactate production, whereas SUN5 knockdown produced reciprocal reductions. Mechanistically, SUN5 activates NF-κB signaling, an effect abolished by the IKK inhibitor BAY11-7082. SUN5 interacts with TRIM28 to enhance IκBα ubiquitination, driving nuclear translocation of phosphorylated P65 and transcriptional upregulation of GLUT1 and LDHA. Xenograft transplantation confirmed that SUN5 knockdown suppresses glycolysis and tumorigenesis in vivo. These findings position the SUN5–TRIM28–IκBα–NF-κB axis as a tractable target for CRC diagnosis and therapy.