Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-026-04936-3
Background The abnormal immune response mediated by CD4+T cells is a key factor in Immune thrombocytopenia(ITP) progression. While Ningxue Shengban Decoction (NXSBD) is an effective therapeutic, its underlying mechanism and targets remain obscure. Aim This study aims to clarify the role of exosomal miR-199a-5p derived from bone marrow mesenchymal stem cells (BMSCs) in immune homeostasis, and to explore the therapeutic effects of exosomes from BMSCs(BMSCs-Exo) pretreated with NXSBD containing serum on ITP. Method We co-cultured CD4+T cells with BMSCs or pre-treated BMSCs-Exo. The proliferation and differentiation of CD4+T cells were then assessed using CFSE staining and flow cytometry (FCM). Additionally, an active ITP murine model was employed to assess the therapeutic efficacy of pre-treated BMSCs-Exo. Platelet counts were measured and organ indices were calculated. Serum autoantibody levels were measured by FCM and ELISA, changes in CD4⁺T cells subsets in the spleen were analyzed by FCM, megakaryocyte number and morphology in bone marrow tissues were examined by H&E staining, and key cytokine levels in mouse serum were quantified by ELISA. Results Our results indicate that the immunomodulatory effect of BMSCs-Exo on CD4+T cells is mediated by miR-199a-5p, and that NXSBD containing serum enhances this effect by increasing miR-199a-5p levels. In an active ITP murine model, BMSCs-Exo treatment significantly ameliorated the pathological features of ITP, as evidenced by increased peripheral platelet counts, reduced spleen and thymus indices, and decreased levels of autoantibodies. Immunophenotypic analysis revealed that an increased percentage of splenic Treg and Th2 cells, and a decreased percentage of Th17 and Th1 cells, were observed after BMSCs-Exo treatment. Additionally, BMSCs-Exo enhanced the production of mature megakaryocytes. Following BMSCs-Exo treatment, the levels of pro-inflammatory cytokines were sharply lowered, whereas anti-inflammatory cytokine levels were markedly elevated. BMSCs-Exo pretreated with NXSBD containing serum exert superior therapeutic efficacy compared with those derived from untreated BMSCs.
Stem Cell Research & Therapy•2025•DOI: 10.1186/s13287-025-04480-6
Background Diabetic foot ulcers (DFU) typically exhibit impaired healing due to dysregulated re-epithelialization and excessive inflammation. Succinate, a key metabolic intermediate, is now understood to regulate inflammation through G Protein-Coupled Receptor 91 (GPR91) and succinate dehydrogenase (SDH), although its role in DFU remains unclear. Methods Co-cultures of M2 macrophages and epithelial cells, along with clinical samples, were used to analyze the expression of GPR91 and SDH. Functional assays were performed using high glucose (HG)-treated M2 macrophages (HG-M2) and an in vivo model. Cytokine and growth factor levels in cell supernatant were measured, and molecular mechanisms were explored via qRT-PCR, flow cytometry, and western blot analysis. Results Elevated glucose concentrations increased succinate levels and disrupted M2 macrophage–epidermal stem cells (EpSCs) interactions. GPR91 knockdown worsened HG-M2 dysfunction, while GPR91 overexpression (OE-GPR91) enhanced anti-inflammatory responses and reduced succinate. OE-GPR91-conditioned medium preserved EpSCs stemness and promoted migration mediated by hepatocyte growth factor (HGF). SDH inhibition (via Dimethyl malonate, DMM) boosted M2 macrophage activity by reducing reactive oxygen species (ROS) and upregulating Gpr91 expression. Mechanistically, GPR91 activated the pAkt/pGSK3β/β-catenin pathway, while DMM enhanced M2 macrophage function via the PI3K-Akt/pERK1/2 pathway. Conclusions GPR91 upregulation and SDH inhibition improve HG-M2 macrophage function, reduce inflammation, and enhance HGF-mediated EpSCs repair. Targeting both pathways may represent a promising approach to promote DFU healing.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025191
The liver is a crucial site for fructose uptake and metabolism, a function intricately linked to fructose-associated pathologies. This study examines the role of hepatic ketohexokinase (KHK) in metabolic syndrome induced solely by high-fructose intake. Liver-specific Khk-deficient mice are generated and fed with a 20% fructose solution for 3 months, after which the features of metabolic syndrome are examined. Compared with fructose-fed floxed controls, fructose-fed liver-specific Khk-deficient mice present alleviated liver injury and hepatic steatosis, along with lower triglyceride levels in the plasma and liver, plasma aspartate transaminase and alanine transaminase levels, and mRNA levels of genes related to triglyceride and fatty acid synthesis. Liver-specific Khk deficiency also leads to lower uric acid levels in the plasma and urine, as well as xanthine oxidase activity and Glut9 mRNA levels in the liver and kidneys of fructose-fed mice. Although intestinal villus length and epithelial barrier integrity remain unaffected, the deletion of liver Khk significantly reduces fructose-stimulated KHK, Glut2, Glut5, and aldolase B expression in the intestine and kidneys, suggesting inhibited fructose absorption and metabolism in these tissues. In the adipose tissue, fructose-induced increases in adipocyte size and tumor necrosis factor-α and interleukin-6 mRNA levels are blocked by liver-specific Khk deficiency, indicating improved remodeling of adipose tissue and reduced inflammation in adipocytes. Overall, liver-specific Khk deletion is sufficient to protect against metabolic syndrome induced by excessive fructose intake. Our findings underscore the critical role of liver KHK-mediated fructose metabolism in driving the physiological and pathological consequences associated with fructose consumption along the intestinal-liver-kidney axis.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2024215
A better understanding of how sympathetic nerves impact pancreatic function is helpful for understanding diabetes. However, there is still uncertainty and controversy surrounding the roles of sympathetic nerves within the pancreas. To address this, we utilize high-resolution imaging and advanced three-dimensional (3D) reconstruction techniques to study the patterns of sympathetic innervation and morphology in the islets of adult wild-type (WT) and diabetic mice. Our data show that more than ~30% of α/β-cells are innervated by sympathetic nerves in both WT and diabetic mice. Additionally, sympathetic innervated α/β-cells are reduced in diet-induced obese (DIO) mice, whereas sympathetic innervated β-cells are increased in db/db mice. In addition, in situ chemical pancreatic sympathetic denervation (cPSD) improves glucose tolerance in WT and db/db mice but decreases glucose tolerance in DIO mice. In situ cPSD also enhances insulin sensitivity in diabetic mice without affecting WT mice. Overall, our findings advance our understanding of diabetes by highlighting the distinctive impact of pancreatic sympathetic innervation on glucose regulation.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025102
Influenza A viruses (IAVs) constitute a major threat to human and animal health. Currently, M2 ion-channel inhibitors, neuraminidase (NA) inhibitors, RNA polymerase inhibitors, and cap-dependent endonuclease inhibitors have been applied clinically as therapeutics against IAVs. However, IAVs possess adaptive mutations to these inhibitors, especially M2 ion channel and NA inhibitors. Thus, novel antiviral agents should be developed. In the present study, we screen approximately 5500 compounds and identify an IAV inhibitor, nanchangmycin, which possesses a robust antiviral activity both in vitro and in vivo. In addition, it exhibits broad-spectrum antiviral activity for additional virus infections, including pseudorabies virus, herpes virus, porcine epidemic diarrhea virus, porcine reproductive and respiratory syndrome virus. Most importantly, it has antiviral activity against oseltamivir-resistant strains in sub-μM ranges and promotes the survival of MDCK cells infected with the oseltamivir-resistant influenza A virus strain. Further studies reveal that it blocks the nuclei migration of viral nuclear proteins (NPs), resulting in NP accumulation in the cytoplasm, particularly within perinuclear endosomes. Also, it inhibits IAVs by blocking endosomal acidification. Overall, nanchangmycin has the potential to be developed as an anti-influenza agent.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025164
Emerging biochemical and genetic evidence has firmly established aberrant protein glycosylation as a critical regulator of oncogenic transformation, with glycocalyx remodeling profoundly influencing tumor microenvironment dynamics and metastatic progression. Despite the well-documented association between metastatic dissemination and poor clinical outcomes in patients with colorectal cancer, the underlying molecular mechanisms remain incompletely characterized. Through integrative analysis of single-cell RNA sequencing data from a public database, we identify the Golgi-resident α-1,2-mannosidase MAN1A1 as a consistently upregulated enzyme in malignant epithelial cells derived from colorectal cancer liver metastases. Clinically, elevated MAN1A1 expression is correlated with reduced overall survival, suggesting that MAN1A1 is both a prognostic biomarker and therapeutic target for colorectal cancer liver metastases. Genetic manipulation of MAN1A1 in colorectal cancer cells demonstrates that although the proliferation capacity of colorectal cancer cells remains unchanged, MAN1A1 overexpression significantly enhances migratory and invasive capacities in transwell assays, suggesting its specific involvement in metastatic progression. Mechanistic investigations reveal that MAN1A1 exerts its pro-metastatic effects by significantly prolonging the TGFBR2 protein half-life. Together, our work identifies MAN1A1 as both a prognostic biomarker and a promising therapeutic target, highlighting the critical role of glycan remodeling in the metastatic progression of colorectal cancer.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025018
Diabetes mellitus (DM) is a risk factor for the development of atrial fibrillation (AF). The action potential duration (APD) has been demonstrated to be prolonged in the atrium of diabetic mice. In contrast, the APD is generally shortened in AF patients. It is unclear what change occurs in the atrial APD of diabetic patients. In this study, we explore the APD change of atrial myocytes from diabetic patients and the underlying molecular mechanisms. The whole-cell patch-clamp technique is used to detect single-cell electrical activity in diabetic and nondiabetic human samples. The results show that both APD50 and APD90, the APD at 50% and 90% repolarization, are increased in diabetic patients compared with those in nondiabetic controls. The density of late sodium current (INaL) in the atrial myocytes of diabetic patients is greater than that in the myocytes of nondiabetic patients. The expression of receptor for advanced glycation end products (RAGE) is increased in the atria of diabetic patients. In cultured HL-1 cells, high glucose (HG) treatment increases INaL, and the expression of RAGE prolongs APD. The siRNA-mediated knockdown of RAGE reduces the INaL and shortens the APD. The APD is prolonged in the atria of diabetic patients because of the upregulation of RAGE and the subsequent increase in INaL. Our findings provide novel insights into atrial electrical remodeling in diabetic patients.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2024202
Dorsal root ganglion (DRG) neurons are responsible for the primary detection and transmission of peripheral noxious stimuli, mainly pain and itch. However, as two distinct noxious sensations, how DRG neurons respond differently to and code pain and itch is still an attractive topic. Here, we investigate the response and activation spectrum of DRG neurons under peripheral pain and itch stimuli using in vivo two-photon calcium imaging and find differences in the response intensity to pain and itch between multisensory neurons (both pain and itch) and single-sensory neurons (either pain or itch). In addition, single-cell RNA sequencing (scRNA-seq) is used to reveal the heterogeneity of distinct subpopulations on the basis of their expressions of pain- or itch-related marker genes and to determine the similarities and differences in their transcriptomic changes under chronic pain and itch. Our results show that primary sensory neurons with different sensory patterns respond differently to the same nociceptive stimuli. Additionally, distinct clusters of neurons exhibit unique transcriptomic changes in the development of chronic pain and itch, which may offer new insights for treating these conditions.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025172
Long noncoding RNAs (lncRNAs) are essential in regulating the development and progression of different types of cancer. However, our insights into their impact and mechanisms in papillary thyroid carcinoma (PTC) are still insufficient. In this study, we investigate the effects of the ferroptosis-associated long noncoding RNA LINC02432 on PTC, which recognizes ferroptosis as a critical mechanism in cancer biology and lncRNAs as significant factors in various malignancies. To identify lncRNAs associated with ferroptosis in PTC, we conduct bioinformatics analyses and perform functional assays to evaluate the biological impact of LINC02432 on PTC cells, as well as its relationship with ferroptosis. Mechanistic studies employ methods such as western blot analysis, flow cytometry, and real-time PCR. Our analysis of transcriptome data from TCGA reveals that LINC02432 is the only lncRNA consistently identified by all 10 machine learning methods used, and its expression is significantly downregulated in PTC. Overexpression of LINC02432 in PTC cells inhibits cell proliferation and migration while promoting ferroptosis through inactivation of the NRF2 pathway. LINC02432 knockdown in PTC cells yields the opposite result. These findings highlight the potential of LINC02432 as a tumor suppressor in PTC progression, offering new insights into the mechanisms underlying the development and progression of this malignancy.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025136
Tumor cells exhibit a notable ability to adapt to constantly changing microenvironments and possess distinct metabolic traits during metastasis. This study aims to establish a melanoma lung metastasis model in mice to elucidate the metabolic mechanisms involved in early-stage metastasis prior to treatment. The male C57BL/6 mice are divided into five groups based on time intervals of 6, 24, 72, and 120 h post-injection (SKCM-M groups) of melanoma cells, as well as a normal control group (NOR group). Our results demonstrate that platelet activation mainly occurs in the initial phases of metastasis to help tumor cells survive. NMR-based metabolomics analysis of mouse lung tissues identifies distinct metabolites and pathways associated with early-stage metastasis, revealing significant alterations in energy and amino acid metabolism during tumor progression. Further analysis indicates that methylxanthine and allantoin could serve as potential biomarkers for monitoring the early progression of tumor metastasis in cancer patients, providing novel insights into early diagnostic strategies for lung metastasis.
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.2025237
Exposure to chronic hypobaric hypoxia provokes marked alterations in the gut microbiota and its metabolome, yet the functional significance of histidine-derived metabolites in hypobaric hypoxic pulmonary hypertension (PH) remains underexplored. Here, we employ 16S rDNA, metagenomic, and untargeted metabolomic sequencing to characterize longitudinal shifts in the fecal microbiota and metabolites during hypobaric hypoxic PH development in Sprague-Dawley rats. Fecal carnosine levels and the abundance of its producer, Ruminococcus bromii, both decrease significantly over 28 days of hypobaric hypoxia (P < 0.05). Spearman correlation shows that carnosine is inversely correlated with the percentage of pulmonary arteriole media thickness (MT%; r = –0.8741, P < 0.001). Therapeutic supplementation with carnosine restores systemic and pulmonary antioxidant defenses and attenuates vascular remodeling without altering right ventricular pressures. In vitro, carnosine inhibits hypoxia-induced pulmonary artery smooth muscle cell (PASMC) proliferation and migration and suppresses nuclear factor erythroid 2-related factor 2 (Nrf2) accumulation. These findings reveal dynamic gut-lung crosstalk in hypobaric hypoxic PH and nominate carnosine as a metabolite-based intervention to mitigate hypoxia-driven pulmonary vascular remodeling.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025065
Stem cell fate is profoundly influenced by a complex interplay of biochemical and biophysical cues, with the latter increasingly recognized for its roles in cellular processes, yet the mechanisms are unclear. Since chromatin accessibility is a critical determinant in the processes of osteogenesis and bone repair, investigating the contributions of open chromatin regions (OCRs) to the intracellular signaling pathways triggered by topographical cues, which lead to osteogenic differentiation is highly valuable. This study explores the impact of the nanotopography of biomaterials on the osteogenic differentiation of human bone marrow stem cells (hBMSCs). By utilizing electrospun poly-L-lactide (PLLA) membranes with random fiber arrangements, we mimic the natural extracellular matrix (ECM) topography to study its effects on hBMSCs, contrasting them with flat PLLA controls. Through high-throughput Assay for Transposase-Accessible Chromatin with sequencing (ATAC-seq) and RNA sequencing (RNA-seq), we reveal that the nanotopography of electrospun surfaces promotes osteogenic differentiation by modulating the chromatin accessibility of the YBX1 gene promoter, leading to its upregulation. Lentiviral knockdown experiments further confirm the crucial role of YBX1, revealing a reversal of the osteogenic effects induced by nanotopography. This study emphasizes the importance of YBX1 in the osteogenic response to the surface topography of biomaterials and suggests that nanotopographical cues could be harnessed to direct stem cell fate. These findings are important for developing biomaterials that promote specific stem cell outcomes in regenerative medicine. Our results further contribute to a deeper understanding of the mechanisms underlying stem cell differentiation in response to environmental cues and pave the way for the rational design of biomaterials with enhanced osteogenic potential. By elucidating the role of chromatin accessibility and specific transcription factors such as YBX1, this study highlights the intricate interplay between cell-material interactions and the intracellular signaling pathways that govern stem cell fate.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2024236
Mitochondrial dysfunction is implicated in numerous disorders, including type 2 diabetes, Alzheimer’s disease and cancer. Long non-coding RNAs (lncRNAs) are emerging as pivotal regulators of cellular energy metabolism, yet their roles remain largely unclear. In this study, we identify an lncRNA named linc-PMB, which is associated with mTOR and promotes mitochondrial biogenesis, through microarray analysis. We demonstrate that the knockdown of linc-PMB results in significantly impaired mitochondrial respiration and biogenesis, along with altered expressions of related genes. Conversely, overexpression of linc-PMB markedly increases mitochondrial function. We further reveal that linc-PMB interacts with the RNA-binding protein HuR, promoting the stabilization of SIRT1 mRNA and a substantial increase in SIRT1 expression, which in turn activates the PGC-1α/mtTFA pathway and mitochondrial biogenesis. Collectively, our findings reveal a novel regulatory pathway in which linc-PMB, through its interaction with HuR, modulates the SIRT1/PGC-1α/mtTFA axis to maintain mitochondrial biogenesis and function.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025122
Long noncoding RNAs (lncRNAs) play crucial roles in the occurrence and progression of hepatocellular carcinoma (HCC), but the functions and molecular mechanisms of large lncRNAs remain unclear. In this study, HCC data from The Cancer Genome Atlas (TCGA) and 116 HCC cases from our clinical center are used to identify a novel lncRNA, RP11-439C15.4, which is significantly downregulated in HCC. This downregulation is associated with poor prognosis in HCC patients. A series of in vitro and in vivo experiments demonstrate that RP11-439C15.4 significantly inhibits the proliferation, invasion, migration and sorafenib resistance of HCC cells. Further mechanistic investigations reveal that RP11-439C15.4 interacts with DExH-Box Helicase 9 (DHX9) to increase its ubiquitination and accelerate the degradation of DHX9, ultimately suppressing HCC progression. Modulation of DHX9 significantly reverses the effects of RP11-439C15.4 in HCC. In conclusion, this study identifies RP11-439C15.4 as a tumor suppressor and elucidates the regulatory mechanism of the RP11-439C15.4/DHX9 axis in HCC, providing valuable insights into the mechanisms of HCC progression and potential therapeutic targets.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2024169
Peripheral nerve injury (PNI) can transform primary somatosensory neurons to a regenerative state. However, the details of the transcriptomic changes associated with the nerve regeneration of somatosensory neurons remain unclear. In this study, single-cell RNA sequencing (scRNA-seq) is conducted on mouse dorsal root ganglion (DRG) cells after the early stage of nerve injury on day 3 after chronic constriction injury (CCI). We observe that a novel CCI-induced neuronal population (CIP) emerge and express high levels of activating transcription factor (Atf3), a neuronal injury marker. CIP neurons highly express regeneration-associated genes (RAGs) and are enriched in regeneration-related gene ontology (GO) terms, suggesting that these neurons can constitute a pro-regenerative population. Moreover, intercellular communication networks show that CIP neurons closely communicate with satellite glial cells (SGCs) and specifically transmit strong Fgf3-Fgfr1 signaling to SGCs, which could initiate regeneration-associated transcriptional changes in SGCs. We also confirm that regenerative progress occurs at the early stage of nerve injury because immunohistochemistry shows that the expression of ATF3 is significantly increased beginning at 3 days post-CCI and decreased at 1 month post-CCI. Our bioinformatics analysis at single-cell resolution advances the knowledge of regenerative dynamic transcriptional changes in DRG cells after injury and the underlying molecular mechanisms involved.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2024138
Chemoresistance is the primary reason for poor prognosis in patients with pancreatic cancer (PC). Recent studies have indicated that ferroptosis may improve chemoresistance, but the underlying mechanisms remain unclear. In this study, significant upregulation of heat shock protein 90α (Hsp90α) expression is detected in the peripheral blood and tissue samples of patients with chemoresistant PC. Further studies reveal that Hsp90α promotes the proliferation, migration, and invasion of a chemoresistant pancreatic cell line (Panc-1-gem) by suppressing ferroptosis. Hsp90α competitively binds to Kelch-like ECH-associated protein 1 (Keap1), liberating nuclear factor erythroid 2-related factor 2 (Nrf2) from Keap1 sequestration. Nrf2 subsequently translocates into the nucleus and activates the glutathione peroxidase 4 (GPX4) pathway, thereby suppressing ferroptosis. This process further worsens the chemoresistance of PC cells. This study provides valuable insight into potential molecular targets to overcome chemoresistance in PC. It sheds light on the intricate mechanisms linking Hsp90α and ferroptosis to chemoresistance in PC and provides a theoretical foundation for the development of novel therapeutic strategies.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024047
The linear ubiquitin chain assembly complex (LUBAC) is the only known E3 ligase complex in which the ubiquitin-like (UBL) domains of SHARPIN and HOIL-1L interact with HOIP to determine the structural stability of LUBAC. The interactions between subunits within LUBAC have been a topic of extensive research. However, the impact of the LTM motif on the interaction between the UBL domains of SHARPIN and HOIL-1L with HOIP remains unclear. Here, we discover that the absence of the LTM motif in the AlphaFold2-predicted LUBAC structure alters the HOIP-UBA structure. We employ GeoPPI to calculate the changes in binding free energy (ΔG) caused by single-point mutations between subunits, simulating their protein-protein interactions. The results reveal that the presence of the LTM motif decreases the interaction between the UBL domains of SHARPIN and HOIL-1L with HOIP, leading to a decrease in the structural stability of LUBAC. Furthermore, using the AlphaFold2-predicted results, we find that HOIP (629‒695) and HOIP-UBA bind to both sides of HOIL-1L-UBL, respectively. The experiments of Gromacs molecular dynamics simulations, SPR and ITC demonstrate that the elongated domain formed by HOIP (629‒695) and HOIP-UBA, hereafter referred to as the HOIP (466‒695) structure, interacts with HOIL-1L-UBL to form a structurally stable complex. These findings illustrate the collaborative interaction between HOIP-UBA and HOIP (629‒695) with HOIL-1L-UBL, which influences the structural stability of LUBAC.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024057
A pathological hallmark of Alzheimer’s disease (AD), the most common neurodegenerative disease in elderly people, is the formation of neurofibrillary tangles (NFTs), which are mainly composed of bundles of amyloid fibrils formed by abnormal deposition of hyperphosphorylated full-length human Tau protein [1–3]. Recent studies have shown that AD-related cognitive decline and brain atrophy are closely correlated with Tau PET signal, further supporting the link between Tau pathology and AD symptomatology [4,5]. Despite the high incidence and severe burden to patients, caregivers, and health systems caused by AD, there are few disease-modifying therapies available. Normal functional human Tau protein binds to tubulin heterodimers through its microtubule-binding repeats and stabilizes microtubules. Hyperphosphorylated Tau detaches from microtubules and exposes the microtubule-binding domain, thereby leading to Tau self-oligomerization and aggregation [6]. Accumulating evidence suggests that filamentous Tau inclusions form first in a small number of brain cells, from which they are released and taken up by neighboring cells via endocytosis; these filamentous Tau inclusions act as templates for their own replication through monomeric Tau addition and propagate to other regions of the cells [7,8]. Propagation of neuropathology is called prion-like, which refers to the capacity of an abnormally assembled protein to induce the same pathological conformation in the same protein, initiating a self-amplifying cascade. Transcellular propagation and prion-like phenomena are thought to contribute to the progression of pathology in AD, suggesting that inhibiting Tau aggregation and seeding could slow disease progression [7,8]. Accordingly, different experimental aggregation models for the Tau protein have been developed. A cell-based model offers a physiological assay environment with controllable costs and reproducible results, making it the most widely used model for the development of Tau-targeted therapies. In most cellular models, self-assembly of naive monomeric Tau is promoted by the addition of an exogenous ‘seed’ template of synthetic or patient-derived pre-aggregated Tau [9]. Pre-prepared fibrillar seeds of Tau are added to the cell culture medium, taken up by cells, and act as templates to induce the aggregation of monomeric Tau. In addition to homotypic seeding, heterotypic seeding has also been demonstrated for Tau. Direct cross-seeding between pre-aggregated Aβ and Tau is supported by direct binding between Aβ peptides and Tau and direct induction of Tau fibrillization by pre-aggregated Aβ seeds [10]. Human-derived seeds are the most relevant source of pathological Tau protein; however, clinical material is not straightforward to obtain and work with, and it is difficult to guarantee the quality and stability of aggregated seeds. In addition, aggregate seeds could damage the integrity of the cell membrane and lead to cytotoxicity. In the present study, we reported the construction of a cell-based model for the aggregation of endogenous Tau protein in cells without pre-prepared seeds. By introducing an aggregation-driven pathological mutant, ΔK280, to the aggregation-prone truncated core fragment of Tau (Tau244‒372, K18), we constructed a stable cell line over-expressing K18-ΔK280. Over-expressed K18-ΔK280 spontaneously aggregated in SH-SY5Y cells, forming amyloid fibrils positive for thioflavin S (ThS) (Figure 1), a fluorescent dye with β-sheet binding properties, which is widely employed to observe amyloid plaque accumulation [10]. Based on the present cellular model, the properties of Tau aggregation after seeding can be further observed. The aggregates formed by K18-ΔK280 induce co-aggregation and phosphorylation of endogenous Tau in SH-SY5Y cells, which can be recognized by AT8 (phosphorylation at Ser202/Thr205) and pS396 (phosphorylation at Ser396) (Figures 2 and 3) because phosphorylation at Ser202, Thr205, and Ser396 occurred in endogenous Tau but not at K18-ΔK280. This model is easy to use and avoids the potential cytotoxicity caused by fibrillar seeds.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024087
The aberrant proliferation and migration of vascular smooth muscle cells (VSMCs) contribute to the development of neointima formation in vascular restenosis. This study aims to explore the function of the long noncoding RNA H19 in neointima formation. A mouse carotid ligation model was established, and human vascular smooth muscle cells (VSMCs) were used as a cell model. lncRNA H19 overexpression promoted VSMC proliferation and migration. Moreover, miR-125a-3p potentially bound to lncRNA H19, and Fms-like tyrosine kinase-1 (FLT1) might be a direct target of miR-125a-3p in VSMCs. Upregulation of miR-125a-3p alleviated lncRNA H19-enhanced VSMC proliferation and migration. Furthermore, rescue experiments showed that enhanced expression of miR-125a-3p attenuated lncRNA H19-induced FLT1 expression in VSMCs. In addition, the overexpression of lncRNA H19 significantly exacerbated neointima formation in a mouse carotid ligation model. In summary, lncRNA H19 stimulates VSMC proliferation and migration by acting as a competing endogenous RNA (ceRNA) of miR-125a-3p. lncRNA H19 may be a therapeutic target for restenosis.
Acta Hydrobiologica Sinica•2026•DOI: 10.3724/1000-3207.2026.2026.0101
High-density crowding stress during the initial feeding stage poses severe challenges to fish health, promoting lipid peroxidation. This study assessed the protective effects of dietary vitamin D3 (VD3) against crowding stress and investigated underlying mechanisms. A two-factor design employed juvenile gibel carp (Carassius auratus gibelio var. CAS V) (0.47±0.03 g/fish) in a 71-day feeding trial with three VD3 concentrations (0, 1000, 5000 IU/kg) under two rearing densities (70 vs. 210 fish/tank). Macroscopic growth showed no significant differences, but hepatic biochemical and molecular profiles revealed severe metabolic burden. High density significantly decreased hepatic GPT activity, while GPx4 activity and GSH content were abnormally elevated. Unsupplemented high-density fish exhibited substantial accumulation of lipid hydroperoxide (LPO) and labile iron (Fe2+). VD3 supplementation significantly reduced hepatic LPO and Fe2+ contents, attenuating ferroptosis markers. Transmission electron microscopy revealed shrunken mitochondria and vanished cristae under high density, mitigated by VD3. Transcriptomic analysis showed differentially expressed genes enriched in ferroptosis, cysteine and methionine metabolism, and fatty acid biosynthesis. qPCR confirmed upregulation of nrf2, gpx4a, prdx6 and downregulation of acsl4a by VD3. In conclusion, high-density rearing triggered hepatic ferroptosis and metabolic dysregulation, while VD3 supplementation ameliorated lipid peroxidation and restored mitochondrial ultrastructure, offering mechanistic insights for nutritional interventions.
Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-026-04936-3
Immune thrombocytopenia (ITP) is an acquired autoimmune disorder characterized by immune-mediated platelet destruction and impaired production, leading to isolated thrombocytopenia. Abnormal CD4+ T cell-mediated immune responses are central to ITP progression. Ningxue Shengban Decoction (NXSBD) is clinically effective, but its mechanism remains obscure. This study investigates the role of exosomal miR-199a-5p derived from bone marrow mesenchymal stem cells (BMSCs) in immune homeostasis and evaluates the therapeutic potential of BMSC-derived exosomes (BMSCs-Exo) pretreated with NXSBD-containing serum on ITP. In vitro, CD4+ T cells were co-cultured with BMSCs or pretreated BMSCs-Exo, and proliferation and differentiation were assessed by CFSE staining and flow cytometry. In vivo, an active ITP murine model was used to evaluate therapeutic efficacy. Platelet counts, organ indices, serum autoantibody levels, splenic CD4+ T cell subsets, megakaryocyte number and morphology, and key cytokine levels were quantified. Results demonstrate that the immunomodulatory effect of BMSCs-Exo on CD4+ T cells is mediated by miR-199a-5p, and NXSBD-containing serum enhances this effect by increasing miR-199a-5p levels. BMSCs-Exo treatment significantly ameliorated ITP pathology, evidenced by increased peripheral platelet counts, reduced spleen and thymus indices, decreased autoantibodies, increased splenic Treg and Th2 cells, decreased Th17 and Th1 cells, enhanced mature megakaryocyte production, and rebalanced cytokine profiles. BMSCs-Exo pretreated with NXSBD-containing serum exhibited superior therapeutic efficacy compared to untreated BMSCs-Exo.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025191
The liver is a crucial site for fructose uptake and metabolism, a function intricately linked to fructose-associated pathologies. This study examines the role of hepatic ketohexokinase (KHK) in metabolic syndrome induced solely by high-fructose intake. Liver-specific Khk-deficient mice are generated and fed with a 20% fructose solution for 3 months, after which the features of metabolic syndrome are examined. Compared with fructose-fed floxed controls, fructose-fed liver-specific Khk-deficient mice present alleviated liver injury and hepatic steatosis, along with lower triglyceride levels in the plasma and liver, plasma aspartate transaminase and alanine transaminase levels, and mRNA levels of genes related to triglyceride and fatty acid synthesis. Liver-specific Khk deficiency also leads to lower uric acid levels in the plasma and urine, as well as xanthine oxidase activity and Glut9 mRNA levels in the liver and kidneys of fructose-fed mice. Although intestinal villus length and epithelial barrier integrity remain unaffected, the deletion of liver Khk significantly reduces fructose-stimulated KHK, Glut2, Glut5, and aldolase B expression in the intestine and kidneys, suggesting inhibited fructose absorption and metabolism in these tissues. In the adipose tissue, fructose-induced increases in adipocyte size and tumor necrosis factor-α and interleukin-6 mRNA levels are blocked by liver-specific Khk deficiency, indicating improved remodeling of adipose tissue and reduced inflammation in adipocytes. Overall, liver-specific Khk deletion is sufficient to protect against metabolic syndrome induced by excessive fructose intake. Our findings underscore the critical role of liver KHK-mediated fructose metabolism in driving the physiological and pathological consequences associated with fructose consumption along the intestinal-liver-kidney axis.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025237
Exposure to chronic hypobaric hypoxia provokes marked alterations in the gut microbiota and its metabolome, yet the functional significance of histidine-derived metabolites in hypobaric hypoxic pulmonary hypertension (PH) remains underexplored. Here, we employ 16S rDNA, metagenomic, and untargeted metabolomic sequencing to characterize longitudinal shifts in the fecal microbiota and metabolites during hypobaric hypoxic PH development in Sprague-Dawley rats. Fecal carnosine levels and the abundance of its producer, Ruminococcus bromii, both decrease significantly over 28 days of hypobaric hypoxia (P < 0.05). Spearman correlation shows that carnosine is inversely correlated with the percentage of pulmonary arteriole media thickness (MT%; r = –0.8741, P < 0.001). Therapeutic supplementation with carnosine restores systemic and pulmonary antioxidant defenses and attenuates vascular remodeling without altering right ventricular pressures. In vitro, carnosine inhibits hypoxia-induced pulmonary artery smooth muscle cell (PASMC) proliferation and migration and suppresses nuclear factor erythroid 2-related factor 2 (Nrf2) accumulation. These findings reveal dynamic gut-lung crosstalk in hypobaric hypoxic PH and nominate carnosine as a metabolite-based intervention to mitigate hypoxia-driven pulmonary vascular remodeling.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21288
BACKGROUND: As crucial stabilizers of the knee joint, the medial collateral ligament and lateral collateral ligament play essential roles in restricting valgus and varus movements, respectively. However, the mechanical differences between the medial collateral ligament and lateral collateral ligament, the microstructure characteristics, and the effect of elastin degradation on their mechanical properties remain poorly understood. OBJECTIVE: To compare the mechanical differences between the medial collateral ligament and lateral collateral ligament, quantify the structural characteristics of the collagen fiber alignment, and investigate the effect of elastin degradation on the mechanical properties of both ligaments. METHODS: Left medial collateral ligaments and lateral collateral ligaments were harvested from adult pigs, frozen, and thawed. Quasi-static uniaxial tensile tests were performed to measure the mechanical properties of the medial collateral ligament and lateral collateral ligament, and the effects of repeated stretching on their mechanical properties were compared. Second harmonic generation imaging using a two-photon microscope was used to quantify the collagen fiber structure of the medial collateral ligament and lateral collateral ligament. After repeated stretching, the medial collateral ligament and lateral collateral ligament were incubated in elastase solution for 12 hours, followed by uniaxial tensile tests to determine the effect of elastin treatment on ligament mechanical properties. RESULTS AND CONCLUSION: (1) Quasi-static uniaxial tensile tests showed that the high-tension elastic modulus of the medial collateral ligament was higher than that of the lateral collateral ligament (P < 0.05), while there was no significant difference in the low-tension elastic modulus between the two groups (P > 0.05). Repeated stretching significantly reduced the low-tension elastic modulus of both the medial collateral ligament and lateral collateral ligament. (2) Elastase treatment significantly reduced the low-tension and high-tension elastic moduli of both the medial collateral ligament and lateral collateral ligament, and the decrease in the high-tension elastic modulus of the lateral collateral ligament was greater than that of the medial collateral ligament. After elastase treatment, both the low-tension and high-tension elastic moduli of the medial collateral ligament were higher than those of the lateral collateral ligament (P < 0.05). (3) Two-photon imaging showed that the collagen fibers of the medial collateral ligament maintained a crimped structure, and its fiber waviness was significantly higher than that of the lateral collateral ligament. (4) These results indicate that the medial collateral ligament has stronger elastic properties than the lateral collateral ligament, and elastase treatment has a greater effect on the mechanical properties of the lateral collateral ligament. These mechanical results may be related to the more crimped collagen fiber arrangement in the medial collateral ligament.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21294
BACKGROUND: Studies have shown that cuproptosis plays a critical role in the pathogenesis and treatment of orthopedic diseases. However, the regulatory roles and mechanisms of cuproptosis in orthopedic-related diseases remain unclear. OBJECTIVE: To review the roles and mechanisms of cuproptosis in orthopedic-related diseases. METHODS: A literature search was conducted in the PubMed database using the following English keywords: "cuproptosis," "copper steady state," "osteoarthritis," "osteoporosis," "rheumatoid arthritis," "osteosarcoma," and "oxidative stress." The search included publications up to March 2025. According to the inclusion criteria, 55 articles were finally included for review. RESULTS AND CONCLUSION: In osteoarthritis, excessive copper ions induce the expression of metal-regulatory transcription factor 1, indirectly activating matrix metalloproteinases and leading to cartilage degradation. Cuproptosis disrupts the tricarboxylic acid cycle and inhibits glutamine metabolism, triggering oxidative stress and accelerating chondrocyte death. In osteoporosis, cuproptosis suppresses glutamine metabolism and mineralization in osteoblasts while promoting osteoclast differentiation, thereby disrupting the balance between bone formation and resorption. In rheumatoid arthritis, copper ions activate the phosphatidylinositol 3-kinase/protein kinase B/mitogen-activated protein kinase signaling pathway, promoting synovial cell abnormal activation and inflammatory factor release, exacerbating joint destruction. In osteosarcoma, high concentrations of copper ions selectively kill tumor cells by targeting ferredoxin 1, inducing mitochondrial dysfunction and proteotoxic stress. The mechanisms of cuproptosis in orthopedic diseases are complex and diverse, involving multiple cell types and signaling pathways. Targeting cuproptosis or its related pathways may provide new strategies for the treatment of orthopedic diseases, such as the application of copper chelators or copper ion carriers, which hold significant clinical potential. Future research should further explore the specific regulatory mechanisms of cuproptosis and its therapeutic value in disease treatment.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21343
BACKGROUND: The occurrence of diabetic encephalopathy may be closely related to neuronal aging, but its underlying molecular mechanism is not fully understood. Therefore, exploring the role of neuronal senescence in diabetic encephalopathy is of great significance for further revealing the pathogenesis of diabetic encephalopathy. OBJECTIVE: To investigate the effect and mechanism of emodin on senescence of HT-22 cells under high glucose conditions. METHODS: HT-22 cells were divided into control group (glucose concentration 25 mmol/L), high glucose group (glucose concentration 55 mmol/L), and high glucose + emodin group (glucose concentration 55 mmol/L, emodin concentration 100 µmol/L) and cultured for 48 h. The growth state of cells in each group was observed under microscope; CCK-8 assay was used to detect cell viability; ELISA was used to detect telomerase reverse transcriptase activity; RT-qPCR and western blot were used to detect the expression of senescence-related proteins P53, P21, and P16; immunofluorescence, RT-qPCR and western blot were used to detect the expression of lamin A/C. RESULTS AND CONCLUSION: Compared with the control group, the high glucose group showed obvious growth inhibition under microscope, characterized by decreased cell number, increased cell volume, and flattened morphology; compared with the high glucose group, the high glucose + emodin group showed significantly increased cell number and more regular morphology. Compared with the control group, cell viability was significantly decreased in the high glucose group (P < 0.0001); compared with the high glucose group, cell viability was significantly increased in the high glucose + emodin group (P < 0.0001). Compared with the control group, telomerase reverse transcriptase activity was significantly decreased in the high glucose group (P < 0.001). Compared with the control group, the expression levels of P53, P21, and P16 were significantly increased in the high glucose group (P < 0.05); compared with the high glucose group, the expression levels of P53, P21, and P16 were significantly decreased in the high glucose + emodin group (P < 0.05). Compared with the control group, the expression level of lamin A/C was significantly decreased in the high glucose group (P < 0.0001); compared with the high glucose group, the expression level of lamin A/C was significantly increased in the high glucose + emodin group (P < 0.05). The results indicate that emodin may slow down the senescence of HT-22 cells induced by high glucose by upregulating the expression of lamin A/C.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21422
BACKGROUND: Osteoporosis is a systemic bone metabolic disease characterized by deterioration of bone microstructure and increased bone fragility. Blood is not only a medium of bone metabolism, but also a major factor in the regulation of bone metabolism. The traditional theory of "osteogenesis-osteoclast" is difficult to fully explain its complex pathogenesis, but bone immunology reveals the core role of the interaction between the immune system and bone, and the effects of blood cells in osteoporosis have become a research hotspot. OBJECTIVE: To summarize the mechanism of action of blood cells in osteoporosis and evaluate its potential for related biomarkers and emerging therapeutic approaches. METHODS: A systematic literature search was conducted in CNKI, Wanfang, PubMed, and Web of Science databases using Chinese and English search terms including "blood cells, osteoporosis, biomarkers, bone metabolism, neutrophils, macrophages, bone marrow mesenchymal stem cells". A total of 65 articles were included for review. RESULTS AND CONCLUSION: Blood cells influence the occurrence and development of osteoporosis through mechanisms such as inflammation, immune response, and metabolic regulation. Blood cell-based biomarkers can serve as indicators for early screening of osteoporosis and provide effective targets for diagnosis and treatment. With advances in CRISPR-Cas9 gene editing, single-cell technology, and novel monoclonal antibody development, blood cells are expected to play an important role in the treatment of osteoporosis.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21502
OBJECTIVE: The therapeutic modalities of physical factor interventions for knee osteoarthritis have been increasingly diversified; however, comprehensive comparative evaluations of their efficacy remain limited. This study aims to compare the efficacy and safety of various physical factor therapies for knee osteoarthritis through a network meta-analysis. METHODS: Randomized controlled trials on physical factor therapy for knee osteoarthritis were retrieved from PubMed, Web of Science, Cochrane Library, EMbase, CNKI, VIP, Wanfang, and CBM databases from inception to July 25, 2025. After literature screening and data extraction, the quality of included studies was assessed using the Cochrane risk-of-bias tool. Statistical analyses were performed using Stata 16.0 and RevMan 5.4.1. RESULTS: A total of 65 studies involving 3,418 patients (1,726 in treatment groups, 1,692 in control groups) were included, covering seven physical factor therapies. Network meta-analysis showed that for improving total effective rate, the top three interventions by surface under the cumulative ranking curve (SUCRA) were pulsed electromagnetic field + conventional rehabilitation, ultrasound + conventional rehabilitation, and transcutaneous electrical stimulation + conventional rehabilitation. For improving visual analogue scale (VAS) score, the top three were transcutaneous electrical stimulation + conventional rehabilitation, extracorporeal shock wave + conventional rehabilitation, and ultrasound + conventional rehabilitation. For improving WOMAC total score, the top three were ultrasound + conventional rehabilitation, pulsed electromagnetic field + conventional rehabilitation, and ultrasound + transcutaneous electrical stimulation + conventional rehabilitation. For reducing WOMAC stiffness score, the top three were transcutaneous electrical stimulation + conventional rehabilitation, ultrasound + conventional rehabilitation, and ultrasound + transcutaneous electrical stimulation + conventional rehabilitation. For improving SF-36 quality of life score, the top three were pulsed electromagnetic field + conventional rehabilitation, extracorporeal shock wave + conventional rehabilitation, and ultrasound + conventional rehabilitation. For improving Lysholm knee score, the top three were ultrasound + conventional rehabilitation, ultrasound + transcutaneous electrical stimulation + conventional rehabilitation, and extracorporeal shock wave + conventional rehabilitation. Regarding adverse events, no serious adverse events were reported; most studies reported only mild skin irritation or allergic reactions. CONCLUSION: Transcutaneous electrical stimulation combined with conventional rehabilitation showed superior advantages in improving VAS and WOMAC stiffness scores; ultrasound combined with conventional rehabilitation performed relatively better in improving Lysholm knee score and WOMAC total score; pulsed electromagnetic field combined with conventional rehabilitation had potential advantages in improving overall quality of life. Each physical factor has its unique advantages, but limited by the quality and quantity of included studies, these conclusions need to be verified by more high-quality, multi-center, large-sample randomized controlled trials.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21501
BACKGROUND: Piezo-type mechanosensitive ion channel components (PIEZO) play a crucial role in cartilage degeneration, inflammation, and pain in osteoarthritis by sensing mechanical stimulation and regulating calcium signaling, potentially serving as an important therapeutic target for osteoarthritis. OBJECTIVE: To systematically review the role of PIEZO ion channels in the pathological mechanisms of osteoarthritis and evaluate their potential as a novel therapeutic target. METHODS: The first author searched CNKI and PubMed databases using Chinese and English search terms including "mechanical stress, Piezo, osteoarthritis, chondrocyte, osteoblast, osteoclast, synovial cell, immune cell" and "Piezo1, osteoarthritis, chondrocyte, osteoblast, osteoclast, synovial membrane, immune cell, GsMTx4" respectively. Literature published from 2000 to 2025 was selected, and 102 articles were finally included for review. RESULTS AND CONCLUSION: Mechanical stress plays a central role in the degeneration of articular cartilage and surrounding tissues. Chronic excessive mechanical stress or unbalanced loading causes chondrocyte damage, apoptosis, and inflammatory responses, thereby accelerating osteoarthritis progression. Known mechanosensors include transient receptor potential channel family, two-pore domain potassium channel family, degenerin/epithelial sodium channel family, and integrin family. PIEZO family is the first group of mechanosensitive cation channel pore proteins discovered in mammalian cells, widely present in human cells, sensing changes in ambient pressure to control Ca2+ influx and thus affect cellular functions. PIEZO ion channels regulate Ca2+ influx by sensing mechanical stimulation of the cell membrane, thereby influencing chondrocytes, osteogenesis, synovial cells, immune cells, and pain perception. Inhibiting PIEZO ion channels may become an effective method for treating arthritis.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21650
BACKGROUND: Cortical bone drilling, cutting, friction, and heat generation can easily cause local temperature rise. If it exceeds the bone tissue tolerance threshold and continues to act, it can lead to complications such as bone necrosis, delayed healing, or prosthesis loosening. The coupling of commonly used clinical parameters such as rotational speed, feed rate, and irrigation significantly affects the degree of thermal accumulation, and there is an urgent need to establish a quantitative tool that can predict the temperature field and heat affected zone to define the safe operating window. OBJECTIVE: To establish a temperature prediction model for cortical bone in orthopedic surgery by analyzing the temperature distribution of cortical bone at different depths and radial directions. METHODS: A three-dimensional transient heat transfer control equation was established to describe the cortical bone drilling process. The moving/distributed heat source method was introduced to characterize the interface heat input caused by the shear of the anterior cutting surface and the friction of the posterior cutting surface, and the temperature field evolution at different radial and depth positions was calculated. Using the inverse heat transfer method, the distribution ratio of heat flux and heat between the tool chip bone interface was inverted under the constraint of a finite temperature sequence of measurement points. The model prediction was further validated through experimental comparison. RESULTS AND CONCLUSION: (1) Inverse heat transfer inversion showed that approximately 11.7% of the total heat entered the cortical bone under given conditions; (2) The established temperature prediction model showed good consistency with fresh porcine bone drilling experiments in terms of peak temperature, onset of temperature rise, and temperature-time curve shape, confirming the reliability of the model for spatiotemporal temperature distribution; (3) In terms of spatial distribution, the closer to the hole wall (radius approaching 2.0 mm), the earlier the temperature rise and the higher the peak; along the depth direction (z=0–5 mm), temperature rise first occurred near the surface and gradually extended to deeper parts; (4) The heat affected zone increased with rotational speed: under conditions of drill diameter 4 mm and feed rate 60 mm/min, the heat affected zone was approximately 0.71 mm at 800 r/min and approximately 0.86 mm at 1,000 r/min; (5) These results indicate that under the premise of controlling drill diameter and feed rate, increasing rotational speed increases bone thermal load and heat affected zone thickness; therefore, clinically, rotational speed and cooling/irrigation strategies need to be optimized synergistically to reduce the risk of thermal bone injury; this model can be used for preoperative parameter screening and intraoperative risk assessment, providing quantitative basis for formulating a 'safe parameter window', improving tool and irrigation protocols, and enhancing patient prognosis.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21533
BACKGROUND: Previous studies have confirmed that the "metabolic memory" effect induced by a sustained high-glucose environment can significantly exacerbate damage in mouse hippocampal neuronal cell lines HT-22. OBJECTIVE: To investigate the effects of glycemic variability and sustained high glucose on apoptosis and the expression of histone deacetylase 4 (HDAC4) and silent information regulator 1 (SIRT1) in mouse hippocampal neuronal HT-22 cells. METHODS: Passage 6 HT-22 cells were cultured in three groups after adherence: control group (25 mmol/L glucose for 3 or 5 days), high glucose group (55 mmol/L glucose for 3 or 5 days), and glycemic variability group (alternating 25 mmol/L and 55 mmol/L glucose every 12 hours for 3 or 5 days). After 3 days of culture, cell morphology was observed under an optical microscope. After 5 days, apoptosis was detected by flow cytometry. Cell viability was measured by CCK-8 assay at 3, 4, and 5 days. Reactive oxygen species (ROS) levels were detected using 2,7-dichlorofluorescein diacetate fluorescent probe at 3 and 5 days. Histone deacetylase (HDAC) content in the supernatant was measured by ELISA. Protein expression of Bax, Bcl-2, Caspase-3, Cleaved Caspase-3, SIRT1, and HDAC4 was detected by western blot, and mRNA expression of Bax, Bcl-2, Caspase-3, SIRT1, and HDAC4 was detected by RT-qPCR. RESULTS AND CONCLUSION: (1) Under the optical microscope, control cells grew well, forming a dense network with interconnected synapses; high glucose and glycemic variability groups showed inhibited growth and reduced synaptic connections. Apoptosis rate was higher in the high glucose group than in the control and glycemic variability groups (P < 0.05), and higher in the glycemic variability group than in the control group (P < 0.05). (2) At 3, 4, and 5 days, cell viability was lower in the high glucose group than in the control and glycemic variability groups (P < 0.05), and lower in the glycemic variability group than in the control group (P < 0.05). (3) At 3 and 5 days, ROS levels were higher in the high glucose group than in the control and glycemic variability groups (P < 0.05), and higher in the glycemic variability group than in the control group (P < 0.05). HDAC content in the supernatant was higher in the high glucose and glycemic variability groups than in the control group (P < 0.05). (4) At 3 and 5 days, protein and mRNA expression of HDAC4, Bax, and Caspase-3 were higher in the high glucose and glycemic variability groups than in the control group (P < 0.05), while SIRT1 and Bcl-2 expression were lower (P < 0.05). Cleaved Caspase-3 protein expression was higher in the high glucose and glycemic variability groups than in the control group (P < 0.05). (5) These results indicate that glycemic variability may induce apoptosis in HT-22 cells by upregulating HDAC4 expression and downregulating SIRT1 expression.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2026021
Macrophages play a pivotal role in bone regeneration, making their polarization a key target for immune regulation and therapeutic intervention. Modulating macrophage polarization represents a promising strategy for enhancing bone repair. Luteolin, a plant-derived flavonoid with well-documented anti-inflammatory properties, has been explored for its role in bone repair. However, its specific effects on macrophage polarization in bone repair remain unclear. This study investigates the role of luteolin in macrophage polarization and its underlying mechanisms. Our findings demonstrate that luteolin promotes M2 polarization while suppressing M1 polarization, as indicated by a reduction in the expression of pro-inflammatory markers, including IL-6 and iNOS, and an increase in the expression of anti-inflammatory factors, such as CD206, IL-10, and TGF-β. Mechanistically, luteolin inhibits STING oligomerization, thereby suppressing the STING-TBK1 pathway and mitigating downstream inflammatory responses. In vivo, in a mouse tibial bone defect model, luteolin effectively alleviates inflammation, facilitates angiogenesis, enhances collagen deposition, and improves bone density. Collectively, these findings highlight the potential of luteolin as a therapeutic agent for bone repair by modulating macrophage polarization and inhibiting STING-TBK1 signaling.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2026093
Transfer RNA (tRNA) acts not only as an indispensable adaptor in protein synthesis but also as a key contributor to tumorigenesis when its regulation is disrupted. This review systematically summarizes aberrant tRNA-related mechanisms in cancer, including altered tRNA expression profiles, abnormal post-transcriptional modifications, dysregulated aminoacylation, production of tRNA-derived small RNAs (tdRs), and defects in tRNA trafficking and translational fidelity. Notably, the metabolically abnormal tumor microenvironment actively shapes tRNA reprogramming to facilitate adaptive survival, while dysregulated tRNA elements, such as specific modifications and tdRs, further drive cancer stem cell properties and therapeutic resistance. Collectively, these alterations reprogram the oncoproteome and signaling networks, thereby promoting tumor cell proliferation, metastasis, immune evasion, and drug resistance. Targeting these mechanisms represents a promising strategy for developing novel cancer therapies. Potential approaches include the use of suppressor tRNAs to restore tumor suppressor gene function, the employment of tdRs to modulate oncogenic signaling pathways, or direct inhibition of enzymes involved in tRNA biogenesis. These strategies aim to remodel the dysfunctional tRNA network in cancer and offer new avenues for innovative treatments.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2026117
SGLT2 inhibitor (SGLT2i)-induced diabetic hyperketonemia is a life-threatening acute complication of diabetes. While celastrol has been reported to have beneficial effects on obesity, its potential role in ketogenesis remains unclear. In this study, celastrol administration significantly attenuates the fasting-induced increase in blood β-hydroxybutyrate levels. Moreover, a 7-day course of celastrol (1 mg/kg/day) leads to reductions in body weight and fat mass. Mechanistically, celastrol specifically downregulates HMGCS2 expression and suppresses hepatic ketogenesis through the inhibition of PPARα expression in the short term (≤ 2 days). However, after prolonged treatment for 7 days, celastrol modulates both PPARα and serum free fatty acid (FFA) levels. Furthermore, the anti-ketogenic effect of celastrol is abolished in Pparα⁻/⁻ mice. Importantly, celastrol effectively ameliorates SGLT2i-induced hyperketonemia. In summary, celastrol curbs hepatic ketone overproduction in a PPARα-dependent manner, indicating its protective potential against SGLT2i-induced hyperketonemia.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2026035
Pulmonary fibrosis (PF) is a life-threatening interstitial lung disease characterized by scarring and inflammation in lung tissues. Aberrant activation of the JAK/STAT and NF-κB signaling pathways is critical in initiating and sustaining the inflammatory processes that drive fibrotic progression. In this study, we identify a novel small-molecule compound, T4015, a 4-indolyl-2-phenylaminopyrimidine derivative, as a dual-pathway inhibitor targeting both JAK/STAT and NF-κB signaling. Dual-luciferase reporter assays demonstrate the potent inhibitory activity of T4015 against these pathways. T4015 effectively suppresses the phosphorylation of STAT3, JAK1, and TYK2 induced by IL-6 and IFN-β, while suppressing LPS-induced NF-κB activation in macrophages. Transcriptome sequencing and pathway enrichment analyses further confirm that T4015 downregulates multiple inflammation-related signaling cascades, including the JAK/STAT, NF-κB, TNF, IL-17, and Toll-like receptor pathways. In a mouse model of bleomycin-induced PF, T4015 treatment significantly improves survival, attenuates collagen deposition, and reduces the expression of pro-inflammatory and profibrotic markers such as IL-6, CCL2, and COL1. Molecular docking and target prediction analyses suggest that T4015 exhibits strong binding affinity for multiple kinases within the JAK/STAT and NF-κB networks, including JAK1, TYK2, JAK2, JAK3, RIPK1, IRAK1/4, TAB1, and ZAP70. Collectively, these results highlight T4015 as a promising therapeutic candidate for PF through its simultaneous inhibition of the JAK/STAT and NF-κB signaling pathways.
Chinese Journal of Pathophysiology•2026•DOI: 10.3969/j.issn.1000-4718.2026.05.014
AIM: Psoriasis is a chronic inflammatory skin disease characterized by keratinocyte hyperproliferation and immune dysregulation, yet the spatial epigenetic and neuroimmune features within the skin remain poorly understood. This study aims to construct a spatial atlas of the neuroimmune and epigenetic microenvironment in psoriasis. METHODS: Formalin-fixed, paraffin-embedded skin tissue samples from five psoriasis patients and four healthy controls were stained with a 33-metal antibody panel targeting immune and epigenetic markers. Imaging data were processed to analyze immune cell composition, spatial relationships, and epigenetic marker distribution in psoriatic lesions. RESULTS: Analysis of over 163,000 cells from five psoriasis patients and four healthy controls revealed that psoriatic lesions have a more complex cellular composition than normal skin, including diverse immune subsets, endothelial cells, keratinocytes, and nerve fibers. Neighborhood analysis showed enrichment of multiple immune cells, such as CD14+ monocytes, CD4+/CD8+ T-lymphocytes (T cells), CD68+ macrophages, CD69+ tissue-resident memory T cells and CD20+ B-lymphocytes (B cells), and nerve fibers around keratinocytes. Notably, positive interactions were observed between cutaneous nerve fibers and specific immune cells (CD8+ T cells and CD68+ macrophages) as well as blood vessels. Additionally, histone H3 lysine 27 trimethylation (H3K27me3) modification was mapped across cell types and found in immune cells adjacent to keratinocytes. CONCLUSION: Imaging mass cytometry delineated the psoriatic microenvironment's multicellular structure integrating epigenetic and neuroimmune components, offering new insights into psoriasis pathogenesis.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025065
Stem cell fate is profoundly influenced by a complex interplay of biochemical and biophysical cues, with the latter increasingly recognized for its roles in cellular processes, yet the mechanisms are unclear. Since chromatin accessibility is a critical determinant in the processes of osteogenesis and bone repair, investigating the contributions of open chromatin regions (OCRs) to the intracellular signaling pathways triggered by topographical cues, which lead to osteogenic differentiation is highly valuable. This study explores the impact of the nanotopography of biomaterials on the osteogenic differentiation of human bone marrow stem cells (hBMSCs). By utilizing electrospun poly-L-lactide (PLLA) membranes with random fiber arrangements, we mimic the natural extracellular matrix (ECM) topography to study its effects on hBMSCs, contrasting them with flat PLLA controls. Through high-throughput Assay for Transposase-Accessible Chromatin with sequencing (ATAC-seq) and RNA sequencing (RNA-seq), we reveal that the nanotopography of electrospun surfaces promotes osteogenic differentiation by modulating the chromatin accessibility of the YBX1 gene promoter, leading to its upregulation. Lentiviral knockdown experiments further confirm the crucial role of YBX1, revealing a reversal of the osteogenic effects induced by nanotopography. This study emphasizes the importance of YBX1 in the osteogenic response to the surface topography of biomaterials and suggests that nanotopographical cues could be harnessed to direct stem cell fate. These findings are important for developing biomaterials that promote specific stem cell outcomes in regenerative medicine. Our results further contribute to a deeper understanding of the mechanisms underlying stem cell differentiation in response to environmental cues and pave the way for the rational design of biomaterials with enhanced osteogenic potential. By elucidating the role of chromatin accessibility and specific transcription factors such as YBX1, this study highlights the intricate interplay between cell-material interactions and the intracellular signaling pathways that govern stem cell fate.