Chinese Journal of New Drugs•2025•DOI: 10.1007/s11770-025-1234-5
Nuclear magnetic resonance (NMR) technology has been widely used in the evaluation of coalbed methane (CBM) reservoirs. This paper focuses on the application of NMR technology in the evaluation of fracturing effect of CBM wells. Based on the analysis of NMR relaxation mechanisms, the T2 spectrum characteristics of coal samples before and after hydraulic fracturing are studied. The results show that NMR T2 spectrum can effectively reflect the development of fractures and the change of pore structure. The fractal dimension of T2 spectrum is introduced to quantitatively characterize the complexity of fractures. Combined with the production data, the relationship between NMR parameters and gas production is established. The research provides a reliable method for the evaluation of fracturing effect and the optimization of fracturing design in CBM wells.
Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-026-05080-8
Physiologically relevant liver models are essential for advancing hepatic disorder research, especially for disease modeling and drug development, yet current in vitro systems fail to adequately recapitulate the architecture and function of the liver. Owing to the accessibility, robust proliferation and multilineage differentiation potential of human induced pluripotent stem cells (iPSCs), liver organoids derived from iPSCs have emerged as a promising resource in hepatology. Despite this promise, the field still faces persistent bottlenecks including incomplete hepatic maturation, insufficient incorporation of non-parenchymal cells (notably immune and stromal populations), phenotypic instability, and a lack of consensus on standardized differentiation protocols. Therefore, this review systematically analyzes the challenges and strategies of iPSC differentiation into liver organoids and the related influencing factors by focusing on multidimensional regulation of hepatobiliary development as well as the effects of cellular origin, culture system and liver microenvironment on hepatic differentiation of iPSCs. Moving forward, priority should be given to the following directions: (1) Elucidating the self-assembly mechanism of liver organoids to enable precise control of hepatobiliary differentiation, thereby better governing organoid morphology and improving reproducibility; (2) Replacing exogenous cytokines with small-molecule compounds at different stages of iPSC differentiation to simplify and standardize differentiation protocols; (3) Advancing liver organoid transplantation as a means to validate physiological functionality and shift cell therapy from passive replacement toward active tissue reconstruction; (4) Integrating artificial intelligence to achieve intelligent and precise regulation of hepatic differentiation.
Stem Cell Research & Therapy•2024•DOI: 10.1186/s13287-024-03844-8
Background The leading cause of end-stage renal disease (ESRD) is diabetic nephropathy (DN). Podocyte damage is an early event in the development of DN. Currently, there is no effective treatment strategy that can slow the progression of DN or reverse its onset. The role of mesenchymal stem cells (MSCs) transplantation in diabetes and its complications has been extensively studied, and diabetic nephropathy has been a major focus. Irbesartan exerts reno-protective effects independent of lowering blood pressure, can reduce the incidence of proteinuria in rats, and is widely used clinically. However, it remains undetermined whether the combined utilization of the angiotensin II receptor antagonist irbesartan and MSCs could enhance efficacy in addressing DN. Methods A commonly used method for modeling type 2 diabetic nephropathy (T2DN) was established using a high-fat diet and a single low-dose injection of STZ (35 mg/kg). The animals were divided into the following 5 groups: (1) the control group (CON), (2) the diabetic nephropathy group (DN), (3) the mesenchymal stem cells treatment group (MSCs), (4) the irbesartan treatment group (Irb), and (5) the combined administration group (MSC+Irb). MSCs (2×10^6 cells/rat) were injected every 10 days through the tail vein for a total of three injections; irbesartan (30 mg/kg/d) was administered by gavage. Additionally, the safety and homing of mesenchymal stem cells were verified using positron emission tomography (PET) imaging. Results The combination treatment significantly reduced the UACR, kidney index, IGPTT, HOMA-IR, BUN, serum creatine, and related inflammatory factor levels and significantly improved renal function parameters and the expression of proteins related to glomerular podocyte injury in rats. Moreover, MSCs can homing target to damaged kidneys. Conclusions Compared to the administration of MSCs or irbesartan alone, the combination of MSCs and irbesartan exerted better protective effects on glomerular podocyte injury, providing new ideas for the clinical application of mesenchymal stem cells.
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.2025209
Given the critical role of the cGAS-STING pathway in antitumor immunity, this study investigates the functional role of STING in head and neck squamous cell carcinoma (HNSCC) to evaluate the therapeutic potential of STING agonists. Analysis of the TCGA-HNSC dataset reveals that elevated expression of the STING-encoding gene TMEM173 is significantly correlated with increased M1 macrophage infiltration and enrichment of macrophage polarization-related signaling pathways. In vitro experiments in which RAW 264.7 cells are co-cultured with tumor cell-conditioned medium demonstrate that the STING agonist MSA-2 effectively reprograms tumor-induced M2-polarized macrophages toward the M1 phenotype. This MSA-2-induced M1 polarization is accompanied by increased expressions of IFN-α, IFN-β, IFN-γ, TNF-α, and IL-6, while the STING inhibitor H-151 reverses these effects. Flow cytometry further reveals that MSA-2 treatment reduces PD-1 and increases MHC II expression on macrophages. Immunohistochemical analysis of clinical samples confirms that high STING expression is correlated with increased numbers of CD68⁺ and CD80⁺ (M1-like) macrophages. In support of translational relevance, analysis of single-cell RNA-seq data from HNSCC patients receiving neoadjuvant immunotherapy indicates that TMEM173 is expressed primarily in T cells and macrophages and that the cGAS-STING pathway score is significantly higher in patients who respond to treatment. Collectively, these findings provide systematic clinical and experimental evidence supporting the potential of STING agonists, such as MSA-2, to enhance antitumor immunity in HNSCC, particularly when combined with immunotherapy.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025088
This corrigendum corrects errors in the original article 'Vitamin B6 prevents Isocarbophos-induced posterior cerebral artery injury in offspring rats through up-regulating S1P receptor expression' published in Acta Biochim Biophys Sin 2021, 53(12): 1691–1701. The errors were found in Figure 2B (Vit B6 + Fingolimod), Figure 5 (Saline), and Figure 7 (Isocarbophos/Control). The correct figures are shown. The authors apologize for the error. The corrigendum does not affect the interpretation of data and conclusions.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025086
Liver regeneration is a critical adaptive response to hepatic injury, requiring precise metabolic reprogramming to meet the energetic and biosynthetic demands of proliferating hepatocytes. While the oncoprotein Gankyrin is well-established as a promoter of liver fibrosis and hepatocarcinogenesis, its role in metabolic adaptations underlying liver regeneration remains unclear. In this study, we demonstrate that Gankyrin deficiency in the liver (Gank△Hep/Y) induces hepatic hypertrophy and aberrant glycogen accumulation. Gankyrin expression is significantly upregulated after partial hepatectomy (PHx), whereas Gank△Hep/Y -PHx mice exhibit impaired liver regeneration. This impairment is marked by a delayed restoration of the liver-to-body weight ratio, blunted glycogenolysis, and reduced fatty acid uptake. Mechanistically, Gankyrin activates Pygl and Cd36, key regulators of glycogenolysis and lipid uptake, respectively. Pharmacological inhibition of PYGL activity retards liver regeneration. Furthermore, we identify a novel interaction between Gankyrin and FOXO1, wherein Gankyrin promotes FOXO1 ubiquitination and subsequent proteasomal degradation. This Gankyrin-dependent suppression of FOXO1 leads to the transcriptional upregulation of Pygl and Cd36, thereby fueling hepatocyte proliferation. Collectively, our findings reveal Gankyrin as a master regulator of liver regeneration, integrating metabolic reprogramming with proliferative signaling through the FOXO1-PYGL/CD36 axis. These insights not only elucidate the mechanistic underpinnings of liver regeneration but also unveil the therapeutic potential of targeting the Gankyrin/FOXO1 pathway to mitigate hepatic insufficiency and enhance regenerative capacity in clinical settings.
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•2025•DOI: 10.3724/abbs.2025061
Glutamine metabolism is a hallmark of cancer metabolism. This study aims to perform a comprehensive and systematic single-cell profile of glutamine metabolism in premalignant and malignant gastric lesions. We use single-cell transcriptomics data from chronic atrophic gastritis (CAG) and early gastric cancer (EGC) lesions and investigate glutamine metabolism features at the single-cell level. Experiments are implemented to validate the expression and biological role of ERO1LB in gastric cancer (GC). A single-cell atlas based on 22511 cells from premalignant and early-malignant gastric lesions is established. Among these cells, epithelial cells constitute the dominant cell population in both CAG and EGC lesions. The activity of glutamine metabolism is higher in epithelial cells from EGC lesions than in those from CAG lesions. Among the epithelial cell subpopulations, glutamine metabolism is more active in the epithelial cell subpopulation cluster_4 in EGCs than in CAG lesions. As a key marker gene of this subpopulation, ERO1LB is experimentally proven to be overexpressed in human GC tissue lesions. In both in vitro and in vivo experiments, overexpression of ERO1LB in GC cells increases glutamine metabolism, facilitates cell growth and migration and prevents cell apoptosis, and vice versa. This study provides insight into the cellular heterogeneity of glutamine metabolism within the gastric mucosa in premalignant and malignant gastric lesions and identifies ERO1LB as a key orchestrator of glutamine metabolism, which may help to identify markers for GC prevention and contribute to our understanding of GC pathogenesis.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025185
Diabetic cardiomyopathy (DCM) is a major complication of diabetes and a leading contributor to heart failure, in which cardiomyocyte senescence plays an increasingly recognized role. However, the underlying mechanisms driving this process remain poorly defined. Here, we identify the (pro)renin receptor (PRR) as a critical mediator of cardiomyocyte senescence in DCM. Using a high-fat diet and streptozotocin (STZ)-induced DCM mouse model, as well as primary cardiomyocytes exposed to high glucose and palmitic acid, we demonstrate that PRR expression is significantly upregulated in diabetic hearts and closely associated with key senescence markers, including SA-β-gal, γ-H2AX, p16, and p21. PRR overexpression exacerbates these senescence phenotypes and promotes the secretion of profibrotic senescence-associated secretory phenotype factors, contributing to increased myocardial fibrosis and cardiac dysfunction. Mechanistically, PRR stabilizes the p53 protein by inhibiting tripartite motif-containing 24 (TRIM24)-mediated ubiquitination and proteasomal degradation, thereby activating the p53-p21 axis. These findings reveal a novel role of the PRR in diabetic myocardial senescence and provide potential therapeutic targets for attenuating DCM progression.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025002
Intervertebral disc degeneration (IDD) is a major cause of low back pain (LBP), and effective therapies are still lacking. Reactive oxygen species (ROS) stress induces NLRP3 inflammasome activation, and this, along with extracellular matrix metabolism (ECM) degradation in nucleus pulposus cells (NPCs), plays a crucial role in the progression of IDD. Daphnetin (DAP) is a biologically active phytochemical extracted from plants of the Genus Daphne, which possesses various bioactivities, including antioxidant properties. In the present study, we demonstrate that DAP significantly attenuates tert-butyl hydroperoxide (TBHP)-induced ECM degradation, oxidative stress and NLRP3 inflammasome activation in NPCs. Furthermore, DAP could facilitate mitophagy to increase the removal of damaged mitochondria, consequently reducing mitochondrial ROS accumulation and alleviating NLRP3 inflammasome activation. Mechanistically, we unveil that DAP activates mitophagy by stimulating the Nrf2/PINK1 signaling pathway in TBHP-induced NPCs. In vivo experiments further corroborate the protective effect of DAP against IDD progression in a rat model induced by disc puncture. Accordingly, our findings reveal that DAP could be a promising therapeutic candidate for the treatment of IDD.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2024157
The biomolecular assemblies (condensates or aggregates) formed by mutant proteins are a pathological hallmark of neurodegenerative diseases. Some RNA-binding proteins (RBPs) are typically prone to aggregation that is closely associated with disease pathologies. These RBPs include numerous well-recognized pathogenic proteins, such as TAR DNA binding protein of 43 kDa (TDP-43), fused in sarcoma (FUS), ataxin-2 (Atx2), and poly(A)-binding protein nuclear 1 (PABPN1). Recent studies have revealed that liquid-liquid phase separation (LLPS), as a mechanism, underlies the highly dynamic and reversible granule formation of RBPs, and highlighted that multivalent RNA molecules play crucial roles in this process. These granules are necessary for diverse physiological functions, such as RNA splicing, trafficking, and even RNA storage, during stress. However, the aberrant phase transition of these mutant RBPs usually results in the formation of solid-like aggregates or inclusions within both the cytoplasm and nucleus. More importantly, aggregates formed by RBPs can sequester specific proteins, RNAs or other interacting partners, consequently contributing to RBP-related pathologies. For example, wild-type PABPN1 forms dynamic nuclear speckles with the assistance of poly(A) RNAs, whereas Ala expansion of PABPN1 results in the formation of aggregates, which are involved in the disease progression of oculopharyngeal muscular dystrophy (OPMD). Although the biological importance of various RBP granules is realized in either the cytoplasm or nucleus, how RNA regulates the formation of granules and the transition to aberrant RBP aggregates remains largely unknown. The interaction of a protein with other biomolecules (proteins, nucleic acids, etc.) is the prerequisite for the protein executing its normal biological function in cells. Identifying protein-protein and protein-RNA interactions is fundamental for the biochemical investigation of an individual protein and for attempts to understand the functional role of the protein. To date, many methods for studying protein-protein interactions have been developed on the basis of various principles, but it is still difficult to clarify whether the interactions between proteins, especially the RBPs involved, are direct or indirect, since RBPs generally bind to diverse RNAs closely and are incorporated into macromolecular ribonucleoprotein (RNP) complexes. We have taken several pairs of RBPs as examples, including TDP-35 (C-terminal 35-kDa fragment of TDP-43) with TDP-43 or TIA1, PABPN1 with a 25-kDa component of the mammalian cleavage factor I complex (CFIm25) and Atx2 with DEAD-box RNA helicase 6 (DDX6), and applied modified co-immunoprecipitation (Co-IP) and supernatant/pellet (S/P) fractionation experiments to characterize the association and sequestration of RBPs by using single-stranded DNA (ssDNA) chimera under ribonuclease (RNase) treatment. We designed several pieces of ssDNA oligonucleotides to mimic particular RNAs in cells that may mediate the association and sequestration of RBPs. The association of RBP proteins generally requires binding with multivalent RNA chains, since the bound RNAs tend to incorporate into a large protein-RNA complex with the help of RNA molecules. In Co-IP assay, especially for RBPs, RNase is often utilized to digest RNA in cell lysates to characterize whether the association of different RBPs is direct or indirect. It is important for us to demonstrate the active role of particular RNAs in the association or interaction of RBPs. Therefore, we designed and synthesized ssDNA chimeras to mimic the corresponding RNA that specifically bind to both RBPs simultaneously. In this case, ssDNA is used for rescuing the association of RBPs under the condition of RNase treatment, since the ssDNA oligonucleotide is resistant to nuclease activity. To design ssDNA chimeras for the RBPs of interest, first, the RNA sequences that bind to the two RPBs should be defined. The ssDNA should contain at least two portions (motifs) that specifically bind to each RBP, and each ssDNA portion may include 2–3 repeats of the binding sequence, so that the ssDNA can be recognized and bound efficiently by each RBP. Notably, the T base in ssDNA may sometimes be replaced with the U base (dU) for some more specific-binding RBPs, such as PABPN1. In the case of TDP-43 with Atx2, the binding specificities of the RNA sequences for TDP-43 and Atx2 are UG-rich and AUUUUU (AU5), respectively; then, the TG repeat portion is designed to bind to TDP-43, and the AT5 repeat is to bind to Atx2. Thus, an integrated method of co-IP and S/P fractionation was applied to characterize the association and sequestration of RBPs by combining ribonuclease (RNase) and ssDNA treatments.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024117
Aberrant DNA methylation patterns in the promoter region of PLCG2 are associated with dysregulated signaling pathways and cellular functions. Its role in colorectal cancer cells is still unknown. In this study, qRT-PCR is used to measure DNMT3B expression in colorectal cancer. Western blot analysis and immunohistochemistry are used to analyze DNMT3B and PLCG2 protein levels in colorectal tissues and cell lines. Cell Counting Kit-8 (CCK-8) and colony formation assays are used to assess the proliferation of colorectal cancer cells. Methylation-specific PCR (MSP) and bisulfite-sequencing PCR (BSP) are used to measure DNA methylation level. Our results show that DNMT3B is overexpressed in colorectal cells in the TCGA datasets according to Kaplan-Meier plots. DNMT3B is significantly overexpressed in tumor tissues compared to that in adjacent nontumor tissues. Western blot analysis results demonstrate high expression of DNMT3B in tumor tissues. Compared to normal colonic epithelial cells, colorectal cancer cell lines exhibit elevated level of PLCG2 methylation. Overexpression of PLCG2 effectively prevents the growth of colorectal cancer xenograft tumors in vivo. PLCG2 is identified as a key downstream regulatory protein of DNMT3B in colorectal cancer. DNMT3B inhibits PLCG2 transcription through methylation of the PLCG2 promoter region. DNMT3B controls colorectal cancer cell proliferation through PLCG2, which is useful for developing therapeutic approaches that target PLCG2 expression for the treatment of colorectal cancer.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024188
DNA replication stress is a significant contributor to spontaneous DNA damage and genome instability. While the impact of p53 deficiency on increasing DNA replication stress is known, the specific molecular mechanism underlying this phenomenon remains poorly understood. This study explores how p53 deficiency induces DNA replication stress by activating mTORC1 through R-loop formation, which is facilitated by the upregulation of RNR. Research has shown that p53 deficiency results in increased γH2AX expression and a higher mutation rate in the HPRT gene. Interestingly, these effects can be alleviated by rapamycin, an mTORC1 inhibitor. Additionally, rapamycin reduces the abundance of R-loop structures in p53KO cells, which is linked to mTORC1’s regulation of ribonucleotide reductase (RNR) level. These findings suggest that p53 deficiency-induced DNA replication stress relies on mTORC1 activation, with the upregulation of RNR expression and R-loop formation. Overall, this study underscores the importance of R-loops in mTORC1 activation-dependent DNA replication stress triggered by p53 deficiency.
Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-026-05080-8
Physiologically relevant liver models are essential for advancing hepatic disorder research, particularly for disease modeling and drug development, yet current in vitro systems inadequately recapitulate liver architecture and function. Human induced pluripotent stem cells (iPSCs) offer accessibility, robust proliferation, and multilineage differentiation potential, making iPSC-derived liver organoids a promising resource in hepatology. However, persistent bottlenecks include incomplete hepatic maturation, insufficient incorporation of non-parenchymal cells (notably immune and stromal populations), phenotypic instability, and lack of standardized differentiation protocols. This review systematically analyzes challenges and strategies in iPSC differentiation into liver organoids, focusing on multidimensional regulation of hepatobiliary development and the effects of cellular origin, culture system, and liver microenvironment. Future priorities include: (1) elucidating self-assembly mechanisms to enable precise control of hepatobiliary differentiation, improving organoid morphology and reproducibility; (2) replacing exogenous cytokines with small-molecule compounds at different stages to simplify and standardize protocols; (3) advancing liver organoid transplantation to validate physiological functionality and shift cell therapy from passive replacement toward active tissue reconstruction; (4) integrating artificial intelligence for intelligent and precise regulation of hepatic differentiation.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21311
BACKGROUND: Alzheimer’s disease (AD) is a neurodegenerative disorder. Although β-amyloid and Tau proteins are core biomarkers for AD diagnosis, their heterogeneity and diagnostic limitations necessitate the exploration of novel biomarkers for disease diagnosis and treatment. OBJECTIVE: To analyze the interaction between N6-methyladenosine (m6A) epitranscriptomic modifications and ferroptosis genes in AD using machine learning, bioinformatics analysis, and experimental validation, to identify characteristic genes for AD pathogenesis, and to reveal their association with immune microenvironment regulation, thereby providing novel biomarkers for early diagnosis and precise treatment of AD. METHODS: Genomic data of human hippocampal tissues from GSE5281, GSE48350 (training sets), and GSE33000 (validation set) in the GEO database were integrated. Differentially expressed m6A regulators in AD were screened in the training sets, and the correlation between m6A and ferroptosis genes was assessed to identify ferroptosis-related differentially expressed genes associated with m6A. Support vector machine recursive feature elimination combined with Boruta feature selection was used to determine AD characteristic genes. Gene set enrichment analysis was performed to dissect functional modules of characteristic genes. A logistic regression model combined with receiver operating characteristic curves was constructed to evaluate the diagnostic efficacy of characteristic genes in the validation set. Single-sample gene set enrichment analysis was applied to quantify immune cell infiltration levels and analyze their regulatory association with characteristic genes. Transcription factor/miRNA-mRNA regulatory networks were predicted using ENCORI, miRWalk 3.0, and NetworkAnalyst databases. Potential therapeutic compounds were screened via the CTD database. qRT-PCR and western blotting were used to validate characteristic genes in hippocampal tissues of APP/PS1 double-transgenic mice. RESULTS AND CONCLUSION: (1) Two significantly differentially expressed m6A regulators, Wilms tumor 1 associated protein (WTAP) and methyltransferase-like protein 14 (METTL14), were identified, with 16 ferroptosis-related genes associated with them. (2) Machine learning identified five core characteristic genes: fumarate hydratase (FH), aspartate aminotransferase (GOT1), HRas proto-oncogene (HRAS), metallothionein 3 (MT3), and SET domain containing 1B (SETD1B). (3) Characteristic genes were functionally enriched in oxidative phosphorylation, Huntington disease, Parkinson disease, fatty acid degradation and metabolism, and proteasome signaling pathways. (4) The logistic regression diagnostic model achieved area under the curve values of 0.873 and 0.904 in the training and validation sets, respectively, indicating excellent diagnostic efficacy. (5) Immune microenvironment analysis showed that HRAS was significantly correlated with chemokine receptor family and plasmacytoid dendritic cell infiltration levels. (6) A regulatory network comprising 5 mRNAs, 37 miRNAs, and 142 transcription factors was constructed, and 71 potential therapeutic drugs were predicted. (7) Experimental validation showed that mRNA and protein expression of GOT1, HRAS, and SETD1B in the hippocampus of APP/PS1 mice were significantly different (P < 0.05 or P < 0.01), consistent with bioinformatics analysis. (8) The results reveal that FH, GOT1, HRAS, MT3, and SETD1B can serve as characteristic genes for AD; immune infiltration correlation analysis suggests that HRAS may serve as a potential immunotherapeutic marker for AD, providing a theoretical basis for early diagnosis and targeted therapy.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21427
BACKGROUND: Due to the relatively special symptoms and anatomical structure of scaphoid fractures, untreated fractures or those with delayed treatment often lead to non-union of the fracture, carpal joint collapse, or loss of function, subsequently resulting in persistent or intermittent pain, swelling, and limited mobility in the carpal joint. Currently, although there are a wide variety of bone grafting techniques and the choice of treatment methods is complex, there is still no consensus on which bone grafting surgical method is superior.
OBJECTIVE: To review the research status of scaphoid nonunion, summarize different bone grafting surgeries for the treatment of nonunion of fractures at home and abroad in recent years, explore the clinical efficacy, advantages and disadvantages of various bone grafting techniques, and provide guidance for clinical diagnosis and treatment.
METHODS: A computer was used to search for relevant articles published in the PubMed, MEDLINE, EMBASE, CNKI, China Medical Library, VIP, and WanFang databases from 1980 to 2024. The Chinese and English search terms were “scaphoid nonunion, surgery, bone graft, bone flap, scaphoid proximal pole.” A total of 687 articles were retrieved, and 54 articles were selected for review through inclusion and exclusion criteria.
RESULTS AND CONCLUSION: (1) Non-vascularized graft is still the mainstream treatment for scaphoid nonunion. Among them, simple cancellous bone transplantation has fast bone formation (healing rate 85%-100%) and is suitable for cases without deformity; cortical cancellous bone has strong support (healing rate 88%-93%), which is more conducive to restoring the morphology of the scaphoid. (2) There is no significant difference in the healing rate between iliac bone and distal radial donors, but the distal radial donor site has fewer complications (5% vs. 18%). (3) Vascularized grafts can significantly improve the efficacy of complex cases: radial styloid bone flap healing rate 81%-92%, pronator quadratus pedicled flap healing rate 93.3%, free medial femoral condyle flap has outstanding effect on joint surface reconstruction (healing rate 95%), free iliac bone flap success rate 91.7%-100%, but high technical requirements. (4) The treatment of scaphoid nonunion needs to follow the principle of individualization: non-vascularized grafts are suitable for simple, well-vascularized fractures, while vascularized grafts are aimed at ischemic necrosis or complex deformities. (5) In the future, standardized imaging evaluation (such as MRI grading), biological enhancement techniques (bone morphogenetic protein 2, 3D printed scaffolds), and the popularization of microsurgery are needed to improve efficacy, while combining patient age and occupational needs to formulate the optimal plan, balancing functional recovery and complication prevention.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21402
BACKGROUND: There are individual differences in the effectiveness of arthroscopic surgery in improving knee osteoarthritis, and subjective scoring scales may be biased in evaluating the clinical efficacy of arthroscopic treatment for knee osteoarthritis. OBJECTIVE: To explore the correlation between gait parameters and joint function recovery in patients with knee osteoarthritis after arthroscopic surgery. METHODS: A total of 98 patients with knee osteoarthritis admitted to Chongqing Armed Police Corps Hospital from October 2023 to October 2024 were selected as the research subjects. According to Lysholm knee function score after 6 months of follow-up, they were divided into the excellent group (n=63) and the fair group (n=35). Clinical data including gender, age, body mass index, disease duration, respiration, heart rate, Kellgren-Lawrence grade, smoking history, drinking history, hypertension history, location of onset, and postoperative complications were collected. The intraoperative and postoperative indicators, as well as the knee joint function scores and gait parameters at different times before and after surgery were compared between the two groups. Multivariate Logistic regression was used to analyze the independent influencing factors of knee joint function recovery. Stratified regression analysis was conducted to explore the impact of different clinical and pathological characteristics after treatment on gait parameters. Generalized estimating equations were used to analyze the differences in gait parameters among patients with different knee joint functions after treatment. Generalized additive models were used to analyze the impact of gait parameters on Lysholm score after treatment. Receiver operating characteristic curves were drawn to analyze the value of gait parameters in judging the recovery of knee joint function after treatment. RESULTS AND CONCLUSION: (1) There were significant differences in age, disease duration, Kellgren-Lawrence grade, and postoperative complications between the excellent and fair groups (P < 0.05). (2) The fair group had longer operation time, more intraoperative blood loss, longer postoperative swelling regression time, and longer rehabilitation time than the excellent group (P < 0.05). (3) After surgery, the fair group had higher Western Ontario and McMaster Universities Osteoarthritis Index and visual analog scale scores, and lower Lysholm score, step frequency, and step speed than the excellent group (P < 0.05). (4) Logistic regression analysis showed that age, Kellgren-Lawrence grade, postoperative complications, and postoperative swelling regression time were independent risk factors affecting knee joint function recovery (P < 0.05). (5) Stratified regression analysis showed that age, Kellgren-Lawrence grade, postoperative swelling regression time, and postoperative complications all had negative effects on step frequency and step speed (β < 0, P < 0.05). (6) Generalized estimating equation analysis showed that the degree of knee joint function recovery was associated with gait characteristics (β > 0, P < 0.05). (7) Generalized additive model analysis showed that the effects of step frequency and step speed on Lysholm score after treatment were linear. (8) Receiver operating characteristic curve analysis showed that the combined detection of step frequency and step speed had higher predictive efficacy (area under the curve > 0.85, P < 0.05). (9) These findings suggest that arthroscopic surgery can improve knee joint function in patients with knee osteoarthritis, and dynamic tracking of postoperative gait parameter changes combined with functional scoring scales reveals the association between step frequency, step speed, and knee joint function outcome, further clarifying its clinical predictive value and providing a new quantitative tool for clinical functional assessment to achieve more precise postoperative rehabilitation guidance.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21456
BACKGROUND: Existing treatments can effectively reduce fracture risk in patients with osteoporosis, but their effectiveness is limited in patients with concurrent inflammatory diseases (such as rheumatoid arthritis) or severe postmenopausal osteoporosis. Therefore, the development of novel therapeutic strategies with both anti-inflammatory and anti-osteoclast properties is of great clinical significance. OBJECTIVE: To develop an innovative Sr²⁺ and bromodomain inhibitor Birabresib-loaded nanocomposite material (Bir@Sr-MBG) and characterize their cytocompatibility and in vitro immunomodulatory, anti-osteoclast differentiation, and osteoclast differentiation-promoting effects. METHODS: (1) Strontium-bioactive glass (Sr-MBG) was synthesized using a modified microemulsion-assisted sol-gel method. Birabresib was loaded into the mesoporous structure of Sr-MBG using an optimized solution adsorption method. The resulting material, designated Bir@Sr-MBG, was characterized for drug encapsulation efficiency, drug loading rate, and in vitro drug release. (2) Primary mouse bone marrow macrophages were cultured with different concentrations of Birabresib or Bir@Sr-MBG, and cytocompatibility was assessed by CCK-8 assay. (3) For immunomodulation, cells were divided into five groups: control, lipopolysaccharide (LPS), LPS+Sr-MBG, LPS+Birabresib, and LPS+Bir@Sr-MBG. After 24 h incubation, immunofluorescence staining for iNOS (M1 marker) and CD206 (M2 marker) was performed; qPCR and ELISA were used to measure expression of IL-1β, IL-6, TNF-α, and IL-4. (4) For osteoclast differentiation, bone marrow macrophages were induced with RANKL and divided into four groups: control, Sr-MBG, Birabresib, and Bir@Sr-MBG. After 5 days, TRAP staining, cytoskeletal staining, and scanning electron microscopy were performed; qPCR was used to measure osteoclast-related genes (CTSK, c-Fos, TRAP, NFATc1). (5) For osteogenic differentiation, rat bone marrow mesenchymal stem cells were cultured in osteogenic medium and divided into five groups: control, LPS, LPS+Sr-MBG, LPS+Birabresib, and LPS+Bir@Sr-MBG. After 7 days, alkaline phosphatase and alizarin red staining were performed; qPCR was used to measure osteogenic genes (ALP, Runx2, OCN, OPN). RESULTS AND CONCLUSION: (1) The drug encapsulation efficiency of Bir@Sr-MBG was 44.82%, drug loading rate was 7.47%, and sustained release of Birabresib was observed for over 168 h. (2) CCK-8 assay showed good cytocompatibility for Birabresib at 0.1-1 μg/mL and Bir@Sr-MBG at 20-200 μg/mL. (3) Immunofluorescence staining showed that Bir@Sr-MBG improved the inflammatory microenvironment by regulating macrophage polarization, with stronger anti-inflammatory effects than Sr-MBG or Birabresib alone. qPCR and ELISA confirmed that Bir@Sr-MBG downregulated pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) and upregulated anti-inflammatory cytokine (IL-4) more effectively than Sr-MBG or Birabresib. (4) TRAP staining, cytoskeletal staining, SEM, and qPCR showed that Bir@Sr-MBG had stronger anti-osteoclast differentiation effects than Sr-MBG or Birabresib. (5) ALP staining, alizarin red staining, and qPCR showed that under inflammatory conditions, Bir@Sr-MBG promoted osteogenic differentiation of rat bone marrow mesenchymal stem cells more effectively than Sr-MBG or Birabresib. (6) These results indicate that Bir@Sr-MBG effectively regulates bone metabolism and improves the bone microenvironment through a dual mechanism, showing significant therapeutic potential for osteoporosis.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21583
BACKGROUND: Hydrogel cardiac patches, with their excellent biocompatibility and tunable mechanical properties, demonstrate significant potential in treating acute myocardial infarction, especially when combined with stem cell technology. Hydrogels modified with active components of traditional Chinese medicine (TCM) can promote the proliferation, differentiation, migration, and homing of stem cells. This synergistic effect provides a new approach for stem cell transplantation therapy based on hydrogel cardiac patches.
OBJECTIVE: To focus on the application scenarios of novel biomaterial hydrogel cardiac patches combined with TCM in the treatment of myocardial infarction, and to discuss their development prospects.
METHODS: PubMed and CNKI databases were searched for literature on TCM combined with hydrogel cardiac patches for the treatment of acute myocardial infarction from January 2010 to January 2025. English search terms included "hydrogel, cardiac patch, myocardial infarction, Chinese medicine, stem cell, drug delivery system"; Chinese search terms included "水凝胶, 心脏贴片, 心肌梗死, 中药, 干细胞, 递药系统". According to inclusion and exclusion criteria, 99 articles were finally included for review.
RESULTS AND CONCLUSION: Hydrogel cardiac patches, with their excellent biocompatibility, tunable mechanical properties, and drug-loading capacity, provide ideal mechanical support and microenvironment for myocardial repair. As a hydrophilic polymer biomaterial, the three-dimensional network structure of hydrogel cardiac patches can highly mimic the physical properties of the natural cardiac extracellular matrix, providing a microenvironment for loaded biological cells to proliferate or maintain activity, and helping cell migration, adhesion, spreading, differentiation, and intercellular connection formation. Hydrogels modified with TCM can load stem cells, fully induce and regulate them, and more effectively perform cell regeneration therapy in the myocardial infarction area to achieve better repair. Therefore, the combined application of TCM and hydrogel cardiac patches has great development potential and prospects. Currently, the combined application mainly focuses on the following aspects: precise sustained-release therapy of TCM active ingredients via hydrogel cardiac patch loading; cell regeneration therapy via induced pluripotent stem cells delivered by TCM-modified hydrogel patches; and repair of cardiac electrophysiological function via TCM combined with conductive hydrogels. In future research, it is necessary to deeply understand the characteristics of hydrogels made from different materials and methods, and the therapeutic effects and mechanisms of TCM monomers and compound extracts, to achieve more combined applications of TCM and hydrogel cardiac patches.
Chinese Journal of Pathophysiology•2026•DOI: 10.3969/j.issn.1000-4718.2026.04.010
AIM: Acute hypoxia can induce transient contraction of coronary arteries, leading to myocardial ischemia and even cardiac dysfunction. However, the precise regulatory mechanisms remain unclear. In this study, we applied various interventions to isolated porcine coronary arteries by modulating cytoplasmic calcium concentrations mediated by calcium channels on the plasma membrane and sarcoplasmic reticulum, aiming to investigate the relationship between hypoxic contraction and intracellular calcium levels as well as calcium sensitization effects. METHODS: Isolated rings of the porcine left anterior descending coronary artery served as the experimental model. Based on distinct intervention targets, four core experimental groups were established. The specific grouping, sample size (n) for each group, and treatments were as follows: (1) nitric oxide (NO)-soluble guanylyl cyclase (sGC) pathway and energy metabolism intervention groups including control (n=5), nitric oxide synthase inhibitor nitro-L-arginine (NLA, 10^-4 mol/L; n=4 to 5), soluble guanylyl cyclase (sGC) antagonist 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 3×10^-5 mol/L; n=5), endothelium-denuded (n=5), normal glucose incubation (n=3), and glucose-free incubation (n=3) groups; (2) calcium source intervention groups including normal calcium control (n=4), calcium-free incubation with 5×10^-3 mol/L ethylene glycol tetraacetic acid (EGTA; n=4), L-type calcium channel antagonist nifedipine (10^-6 mol/L; n=5 to 7), non-selective cation channel inhibitor NiCl2 (5×10^-5 mol/L; n=5 to 7), sarcoplasmic reticulum Ca²⁺-ATPase inhibitor thapsigargin (2×10^-6 mol/L; n=5 to 7), and inositol trisphosphate (IP3) receptor antagonist 2-aminoethoxydiphenyl borate (2-APB, 10^-4 mol/L; n=5 to 7) groups; (3) myosin light chain kinase (MLCK) pathway intervention groups including control (n=4) and MLCK-specific inhibitor 1-(5-iodonaphthalene-1-sulfonyl)-1H-hexahydro-1,4-diazepine hydrochloride (ML-7, 10^-5 mol/L; n=6) groups; (4) myosin light chain phosphatase (MLCP) activity and endothelium-dependence intervention groups including endothelium-intact (n=4) and mechanically endothelium-denuded (n=6) groups. All arterial rings were pre-contracted with either U46619 (3×10^-7 mol/L) or KCl (6×10^-2 mol/L) and then subjected to 10 minutes of hypoxia (95% N2+5% CO2). Changes in vascular tension were continuously monitored and recorded using a multi-channel physiological signal acquisition system. Furthermore, combined with Western blotting, the phosphorylation level of myosin light chain (MLC) and the activity of MLCP were determined; the phosphorylation levels of MLC and MLCP were also compared between endothelium-intact and endothelium-denuded coronary arteries under hypoxic conditions. RESULTS: (1) Hypoxic constriction of porcine coronary arteries is dependent on the activation of endothelium-derived nitric oxide (NO) and sGC in vascular smooth muscle cells. (2) Hypoxic contraction in porcine coronary arteries is independent of extracellular Ca²⁺ influx. (3) Hypoxic contraction in porcine coronary arteries does not rely on intracellular Ca²⁺ release from the sarcoplasmic reticulum. (4) Hypoxic contraction in porcine coronary arteries leads to inhibition of myosin light chain phosphatase activity, suggesting increased calcium sensitization in coronary artery smooth muscle. CONCLUSION: The mechanism underlying acute hypoxia-induced vasoconstriction exhibits distinct characteristics: it does not rely on extracellular calcium influx mediated by plasma membrane calcium channels, nor is it associated with intracellular calcium mobilization from sarcoplasmic reticulum stores. Instead, it is mediated by a significant enhancement in calcium sensitivity regulated by myosin light chain phosphatase, a process referred to as calcium sensitization.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025061
Glutamine metabolism is a hallmark of cancer metabolism. This study performed a comprehensive single-cell profile of glutamine metabolism in premalignant and malignant gastric lesions using single-cell transcriptomics data from chronic atrophic gastritis (CAG) and early gastric cancer (EGC). A single-cell atlas based on 22,511 cells was established. Epithelial cells constituted the dominant population in both CAG and EGC lesions. Glutamine metabolism activity was higher in epithelial cells from EGC than in those from CAG. Among epithelial subpopulations, cluster_4 exhibited elevated glutamine metabolism in EGC. ERO1LB, a key marker gene of this subpopulation, was experimentally validated to be overexpressed in human GC tissue lesions. In vitro and in vivo experiments demonstrated that ERO1LB overexpression in GC cells increased glutamine metabolism, facilitated cell growth and migration, and prevented apoptosis, while targeted suppression reversed these effects. The study provides insight into the cellular heterogeneity of glutamine metabolism within the gastric mucosa in premalignant and malignant lesions and identifies ERO1LB as a key orchestrator of glutamine metabolism, potentially aiding in the identification of markers for GC prevention and contributing to the understanding of GC pathogenesis. Limitations include the preliminary nature of the evidence for ERO1LB's role in CAG-induced carcinogenesis, necessitating further mechanistic studies.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025202
Gastric cancer (GC) remains the fifth most common malignancy and third leading cause of cancer-related mortality worldwide, with over 60% of cases occurring in East Asia. Despite advances in endoscopic screening and perioperative FLOT regimens, the 5-year survival rate for advanced or metastatic GC is still below 20%. This study investigates the expression and mechanistic role of V-set and immunoglobulin domain containing 2 (VSIG2) in GC progression. Western blot, qRT-PCR, and immunohistochemical staining revealed that VSIG2 is abnormally downregulated in GC tissues and cells, and its low expression correlates with tumor size, lymph node metastasis, TNM stage, and vascular invasion. Kaplan-Meier analysis confirmed that reduced VSIG2 expression is associated with poor patient prognosis. Functional assays, including CCK-8, EdU, Transwell, and wound healing in vitro, as well as nude mouse subcutaneous tumor and liver metastasis models in vivo, demonstrated that VSIG2 inhibits GC growth, proliferation, and metastasis. Mechanistically, co-immunoprecipitation and immunofluorescence showed that VSIG2 directly interacts with ANXA2 and co-localizes at the cell membrane. VSIG2 competes with FBXW10 for ANXA2 binding, relying on FBXW10-mediated K63 polyubiquitination of ANXA2 to induce its membrane localization and subsequent inactivation of NF-κB signaling. These findings establish VSIG2 as a membrane-localized tumor suppressor that restrains GC progression by blocking the ANXA2–FBXW10–NF-κB axis, offering a potential therapeutic target for high-risk gastric cancer patients.