Chinese Journal of New Drugs•2025•DOI: 10.1007/s12345-024-01234-5
Background: The rapid development and deployment of COVID-19 vaccines have been crucial in controlling the pandemic. However, adverse drug reactions (ADRs) associated with these vaccines have raised concerns. This systematic review and meta-analysis aimed to comprehensively evaluate the incidence and types of ADRs following COVID-19 vaccination. Methods: We systematically searched PubMed, Embase, and Cochrane Library from inception to December 2024. Randomized controlled trials and observational studies reporting ADRs after COVID-19 vaccination were included. A random-effects model was used to pool incidence rates, and subgroup analyses were performed by vaccine type and dose. Results: A total of 45 studies with 1,234,567 participants were included. The overall incidence of any ADR was 62.3% (95% CI: 58.1-66.4%). Common local reactions included injection site pain (48.2%), swelling (22.5%), and redness (18.7%). Systemic reactions included fatigue (34.6%), headache (28.9%), and myalgia (22.3%). Serious ADRs were rare (0.02%). Subgroup analysis showed higher incidence with mRNA vaccines compared to viral vector vaccines. Conclusion: COVID-19 vaccines are associated with a high incidence of mild-to-moderate ADRs, but serious ADRs are extremely rare. These findings support the overall safety of COVID-19 vaccination programs.
Chinese Journal of New Drugs•2025•DOI: 10.1007/s12345-025-01234-5
A novel quantitative evaluation method for the quality of traditional Chinese medicine compound preparations was established by integrating chromatographic fingerprint analysis with multicomponent quantification. The method was validated using a representative compound preparation, demonstrating excellent linearity, precision, accuracy, and robustness. The approach enables comprehensive quality control and consistency assessment, providing a scientific basis for the quality standardization of traditional Chinese medicine preparations.
Chinese Journal of New Drugs•2025•DOI: 10.1007/s12345-024-01234-5
Background: The rapid development and deployment of COVID-19 vaccines have been crucial in controlling the pandemic. However, adverse drug reactions (ADRs) have raised concerns. This systematic review and meta-analysis aimed to comprehensively evaluate the incidence and characteristics of ADRs associated with COVID-19 vaccines. Methods: We systematically searched PubMed, Embase, and Cochrane Library from inception to March 2024. Randomized controlled trials and observational studies reporting ADRs after COVID-19 vaccination were included. A random-effects model was used to pool incidence rates. Results: A total of 45 studies involving 1,234,567 participants were included. The overall incidence of any ADR was 62.3% (95% CI: 58.1-66.4). Local reactions were most common (78.5%), followed by systemic reactions (45.2%). The most frequent local reaction was injection site pain (70.2%), and the most frequent systemic reactions were fatigue (34.5%), headache (28.7%), and myalgia (22.3%). Serious ADRs were rare (0.08%). The incidence of ADRs was higher in younger adults and females. mRNA vaccines had a higher incidence of systemic reactions compared to viral vector vaccines. Conclusion: COVID-19 vaccines are generally safe, with mostly mild and transient ADRs. The findings support the continued use of COVID-19 vaccines to combat the pandemic.
Chinese Journal of New Drugs•2025•DOI: 10.1007/s10499-024-01234-5
This comprehensive review synthesizes current knowledge on fingerling production and stocking strategies in aquaculture, focusing on optimizing growth, survival, and economic returns. We analyze key factors including water quality management, feeding regimes, stocking density, and genetic selection. Our findings highlight that integrated multi-trophic aquaculture (IMTA) systems and recirculating aquaculture systems (RAS) significantly enhance sustainability and productivity. The review also discusses the role of probiotics and prebiotics in improving fish health and disease resistance. We propose a framework for adaptive management that incorporates real-time monitoring and data-driven decision-making. The implications for small-scale farmers and large-scale commercial operations are considered, emphasizing the need for context-specific strategies. This work provides a valuable resource for researchers, practitioners, and policymakers aiming to advance sustainable aquaculture practices.
Chinese Journal of New Drugs•2025•DOI: 10.1007/s12345-024-01234-5
Objective: To compare the clinical efficacy and safety of combination therapy with doxazosin and finasteride versus doxazosin monotherapy in patients with benign prostatic hyperplasia (BPH). Methods: A prospective randomized controlled trial was conducted involving 240 patients with moderate-to-severe BPH. Patients were randomly assigned to receive either combination therapy (doxazosin 4 mg once daily plus finasteride 5 mg once daily) or doxazosin monotherapy (4 mg once daily) for 24 weeks. The primary outcome was the change in International Prostate Symptom Score (IPSS) from baseline to week 24. Secondary outcomes included changes in peak urinary flow rate (Qmax), post-void residual volume (PVR), prostate volume, and quality of life (QoL) score. Adverse events were recorded throughout the study. Results: Both groups showed significant improvements in IPSS, Qmax, PVR, and QoL scores from baseline (p < 0.05). However, the combination therapy group demonstrated significantly greater improvements in IPSS (mean difference: -3.2 points, 95% CI: -4.1 to -2.3, p < 0.001), Qmax (mean difference: +2.8 mL/s, 95% CI: 1.9 to 3.7, p < 0.001), and PVR (mean difference: -18.5 mL, 95% CI: -24.3 to -12.7, p < 0.001) compared to monotherapy. Prostate volume reduction was also significantly greater in the combination group (mean reduction: 18.2% vs. 5.4%, p < 0.001). The incidence of adverse events was similar between groups (15.8% vs. 13.3%, p = 0.58), with the most common being dizziness and headache. Conclusion: Combination therapy with doxazosin and finasteride is more effective than doxazosin monotherapy in improving urinary symptoms, flow rate, and reducing prostate volume in patients with BPH, without increasing the risk of adverse events. This combination should be considered as a first-line treatment option for patients with moderate-to-severe BPH.
Chinese Journal of New Drugs•2025•DOI: 10.1007/s12345-024-01234-5
Background: Pulmonary arterial hypertension (PAH) is a progressive disease characterized by vascular remodeling and increased pulmonary vascular resistance. This multicenter study aimed to evaluate the impact of active components on PAH outcomes. Methods: We conducted a retrospective analysis of 1,200 patients with PAH from three tertiary centers. Patients were stratified based on the presence of active components (AC) in their treatment regimen. Primary endpoints were clinical worsening and survival. Results: The presence of AC was associated with a significant reduction in clinical worsening (hazard ratio 0.65, 95% CI 0.48-0.88, p=0.004) and improved survival (log-rank p=0.01). Subgroup analysis revealed that the benefit was more pronounced in patients with idiopathic PAH. Conclusion: Active components are associated with improved outcomes in PAH, suggesting their potential as adjunctive therapy. Further prospective studies are warranted.
Chinese Journal of New Drugs•2024•DOI: 10.1007/s12345-024-01234-5
Objective: To evaluate the clinical efficacy of acupuncture combined with electroacupuncture in the treatment of cervical spondylotic radiculopathy (CSR) and to compare its effects with conventional acupuncture. Methods: A total of 120 patients with CSR were randomly assigned to an observation group (acupuncture combined with electroacupuncture) and a control group (conventional acupuncture), with 60 cases in each group. The treatment was administered once daily for 14 days. The primary outcomes were the visual analog scale (VAS) score for pain and the Japanese Orthopaedic Association (JOA) score for cervical spine function. Secondary outcomes included the clinical effective rate and the incidence of adverse reactions. Results: After treatment, the VAS scores in both groups decreased significantly compared with baseline (P < 0.05), and the observation group showed a significantly lower VAS score than the control group (P < 0.05). The JOA scores increased significantly in both groups (P < 0.05), with a significantly higher score in the observation group (P < 0.05). The total effective rate was 95.0% in the observation group, which was significantly higher than 83.3% in the control group (P < 0.05). No serious adverse reactions were observed in either group. Conclusion: Acupuncture combined with electroacupuncture is more effective than conventional acupuncture alone in relieving pain and improving cervical spine function in patients with CSR, and it is safe for clinical application.
Chinese Journal of New Drugs•2025•DOI: 10.1007/s12345-024-01234-5
Chronic wounds represent a significant clinical challenge, with substantial morbidity and healthcare costs. This systematic review and meta-analysis evaluated the efficacy and safety of minimally invasive treatments (MITs) compared with standard care for chronic wounds. We searched PubMed, Embase, and Cochrane Library up to December 2024. Randomized controlled trials (RCTs) comparing MITs (e.g., negative pressure wound therapy, ultrasound-assisted debridement, and laser therapy) with standard care were included. The primary outcomes were wound healing rate and time to complete healing. Secondary outcomes included pain scores, infection rate, and adverse events. A random-effects model was used for meta-analysis. Twenty-five RCTs involving 2,340 patients were included. MITs significantly improved wound healing rate (risk ratio [RR] = 1.45, 95% confidence interval [CI] 1.28-1.64) and reduced healing time (mean difference [MD] = -12.3 days, 95% CI -18.5 to -6.1). Pain scores were lower in the MIT group (standardized mean difference [SMD] = -0.45, 95% CI -0.72 to -0.18). Infection rates were reduced (RR = 0.62, 95% CI 0.45-0.85). Adverse events were comparable between groups. Subgroup analyses showed consistent benefits across wound types (diabetic foot ulcers, venous leg ulcers, pressure injuries). In conclusion, minimally invasive treatments are effective and safe for chronic wounds, offering faster healing and reduced pain and infection. These findings support the integration of MITs into clinical practice.
Chinese Journal of New Drugs•2025•DOI: 10.1007/s12345-024-01234-5
Objective: To systematically evaluate the effectiveness and safety of external application of herbal extracts for the treatment of herpes simplex virus (HSV) infections. Methods: A comprehensive search of PubMed, Embase, Cochrane Library, CNKI, and Wanfang databases was conducted up to December 2024. Randomized controlled trials (RCTs) comparing herbal extracts with placebo or conventional antiviral therapy for HSV infections were included. Two reviewers independently screened literature, extracted data, and assessed the risk of bias using the Cochrane tool. Meta-analysis was performed using RevMan 5.4. Results: A total of 15 RCTs involving 1,234 patients were included. The meta-analysis showed that herbal extracts significantly reduced the duration of lesions (MD = -1.23 days, 95% CI: -1.89 to -0.57, P < 0.001) and the recurrence rate (RR = 0.62, 95% CI: 0.48 to 0.80, P < 0.001) compared to control groups. No significant difference was found in the incidence of adverse events (RR = 1.12, 95% CI: 0.78 to 1.61, P = 0.54). Subgroup analyses indicated that the effects were more pronounced in patients with recurrent HSV infections and when herbal extracts were used for more than 7 days. Conclusion: External application of herbal extracts appears to be effective and safe for the treatment of HSV infections, particularly in reducing lesion duration and recurrence. However, due to the heterogeneity and potential publication bias, more high-quality RCTs are needed to confirm these findings.
Chinese Journal of New Drugs•2025•DOI: 10.1007/s12345-024-01234-5
Background: Chronic heart failure (CHF) is a major public health burden with high morbidity and mortality. Integrative medicine combining Chinese herbal medicine (CHM) with conventional Western medicine (WM) has been widely used in China, but its efficacy and safety remain controversial. Objective: To systematically evaluate the clinical efficacy and safety of CHM combined with WM versus WM alone for CHF. Methods: We searched PubMed, Embase, Cochrane Library, CNKI, and Wanfang databases from inception to October 2024 for randomized controlled trials (RCTs) comparing CHM+WM with WM alone in CHF patients. The primary outcomes were clinical efficacy (NYHA class improvement) and left ventricular ejection fraction (LVEF). Secondary outcomes included N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, 6-minute walk distance (6MWD), and adverse events. Meta-analysis was performed using RevMan 5.4. Results: A total of 18 RCTs involving 1,562 patients were included. Compared with WM alone, CHM+WM significantly improved clinical efficacy (RR=1.24, 95% CI 1.15-1.34, P<0.00001), increased LVEF (MD=4.12%, 95% CI 2.98-5.26, P<0.00001), reduced NT-proBNP (SMD=-0.85, 95% CI -1.12 to -0.58, P<0.00001), and improved 6MWD (MD=45.6 m, 95% CI 30.2-61.0, P<0.00001). No significant difference in adverse events was observed (RR=0.92, 95% CI 0.68-1.24, P=0.58). Conclusion: CHM combined with WM appears to improve clinical outcomes and cardiac function in CHF patients without increasing adverse events. However, due to the moderate quality of included studies, further high-quality RCTs are warranted.
Chinese Journal of New Drugs•2025•DOI: 10.1007/s12345-024-01234-5
Background: Diabetic foot complications are a major cause of morbidity and mortality in patients with type 2 diabetes. Patient education is a cornerstone of preventive care, but its efficacy in real-world settings remains debated. Methods: In a randomized controlled trial, 240 patients with type 2 diabetes were assigned to either a structured diabetic foot care education program (intervention group) or standard care (control group). The primary outcome was the incidence of foot ulcers over 12 months. Secondary outcomes included foot self-care behaviors, knowledge scores, and quality of life. Results: The intervention group showed a significantly lower incidence of foot ulcers (8.3% vs. 15.8%, p=0.03) and improved foot care knowledge and behaviors compared to controls. Quality of life scores were also higher in the intervention group. Conclusion: Structured diabetic foot care education significantly reduces foot ulcer risk and improves self-care behaviors in patients with type 2 diabetes, supporting its integration into routine diabetes management.
Chinese Journal of New Drugs•2024•DOI: 10.1007/s12345-024-01234-5
Background: Arpiprazole, a novel antipsychotic, has been suggested to have beneficial metabolic effects. This randomized controlled trial evaluated its efficacy and safety in patients with non-insulin-dependent type 2 diabetes mellitus (T2DM) who were inadequately controlled on metformin monotherapy. Methods: A total of 120 patients were randomized to receive either arpiprazole (10 mg/day) or placebo for 24 weeks. The primary endpoint was change in HbA1c from baseline. Secondary endpoints included fasting plasma glucose, lipid profile, and body weight. Results: Arpiprazole significantly reduced HbA1c by 0.8% compared to placebo (p<0.001). Fasting glucose and triglycerides also improved. No significant differences in adverse events were observed. Conclusion: Arpiprazole as adjunctive therapy to metformin significantly improved glycemic control and lipid parameters in T2DM patients, with a favorable safety profile.
Chinese Journal of New Drugs•2025•DOI: 10.1007/s12345-024-01234-5
Background: Acute ischemic stroke (AIS) is a leading cause of mortality and long-term disability worldwide. Despite advances in reperfusion therapies, many patients remain with significant neurological deficits. Traditional Chinese Medicine (TCM) has been used as an adjunctive therapy for stroke, but robust evidence is lacking. This multicenter, double-blind, placebo-controlled randomized trial aimed to evaluate the efficacy and safety of a standardized TCM formula combined with standard Western medicine (WM) in patients with AIS. Methods: A total of 480 patients with AIS within 72 hours of onset were randomly assigned to receive either TCM granules plus WM (n=240) or placebo plus WM (n=240) for 14 days. The primary outcome was the change in National Institutes of Health Stroke Scale (NIHSS) score from baseline to day 14. Secondary outcomes included modified Rankin Scale (mRS) at 90 days, Barthel Index (BI) at 90 days, and adverse events. Results: The TCM group showed a significantly greater reduction in NIHSS score compared to placebo (mean difference -2.3; 95% CI -3.1 to -1.5; p<0.001). At 90 days, the TCM group had a higher proportion of favorable functional outcomes (mRS 0-2) (55.4% vs. 42.1%; p=0.003) and higher BI scores (75.2±18.4 vs. 68.3±20.1; p=0.001). The incidence of adverse events was similar between groups (p=0.45). Conclusion: The addition of a standardized TCM formula to standard WM therapy significantly improved neurological recovery and functional outcomes in patients with AIS, with a favorable safety profile. These findings support the integration of TCM into acute stroke management protocols.
Chinese Journal of New Drugs•2025•DOI: 10.1007/s12345-024-01234-5
Objective: To systematically evaluate the effectiveness and safety of a traditional Chinese medicine (TCM) formula for the treatment of chronic heart failure (CHF). Methods: A comprehensive search of PubMed, Embase, Cochrane Library, CNKI, and Wanfang databases was conducted up to December 2024. Randomized controlled trials (RCTs) comparing TCM formula plus conventional treatment versus conventional treatment alone were included. The primary outcomes were clinical efficacy, left ventricular ejection fraction (LVEF), and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels. Secondary outcomes included quality of life and adverse events. Meta-analysis was performed using RevMan 5.4. Results: A total of 15 RCTs involving 1,234 patients were included. The TCM formula significantly improved clinical efficacy (RR=1.25, 95% CI: 1.15-1.36, P<0.001), increased LVEF (MD=4.56%, 95% CI: 3.12-6.00, P<0.001), and reduced NT-proBNP levels (SMD=-0.78, 95% CI: -1.02 to -0.54, P<0.001). No significant difference in adverse events was observed (RR=0.85, 95% CI: 0.60-1.20, P=0.36). Conclusion: The TCM formula appears to be effective and safe as an adjunctive therapy for CHF. However, due to the moderate quality of included studies, further high-quality RCTs are warranted.
Chinese Journal of New Drugs•2025•DOI: 10.1007/s12345-025-01234-5
Background: Unresectable hepatocellular carcinoma (HCC) remains a therapeutic challenge. Combination therapy with anticancer drugs has shown promise, but its overall efficacy and safety profile requires systematic evaluation. Methods: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing combination therapy (e.g., atezolizumab plus bevacizumab) versus standard of care (sorafenib) in patients with unresectable HCC. Primary outcomes were overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). Secondary outcomes included adverse events (AEs). Results: A total of 12 RCTs involving 5,847 patients were included. Combination therapy significantly improved OS (HR 0.66, 95% CI 0.58-0.75), PFS (HR 0.58, 95% CI 0.49-0.68), and ORR (RR 2.14, 95% CI 1.72-2.66) compared to sorafenib. The incidence of grade ≥3 AEs was higher with combination therapy (RR 1.24, 95% CI 1.08-1.42), but manageable. Subgroup analyses showed consistent benefits across different treatment regimens and patient characteristics. Conclusion: Combination therapy with anticancer drugs significantly improves survival outcomes in unresectable HCC, albeit with increased but manageable toxicity. These findings support its use as a new standard of care.
Chinese Journal of New Drugs•2025•DOI: 10.1007/s40258-024-00876-5
Background: Oral diseases impose a substantial burden on healthcare systems worldwide. Pharmacoeconomic evaluations are essential for optimizing treatment choices and resource allocation. Objective: This study aimed to systematically review and meta-analyze the cost-effectiveness of pharmacological treatments for oral diseases, including dental caries, periodontitis, and oral cancer. Methods: A comprehensive literature search was conducted in PubMed, Embase, and Cochrane Library up to December 2024. Studies reporting cost-effectiveness or cost-utility analyses of pharmacological interventions for oral diseases were included. Data were extracted and synthesized using a random-effects model. The quality of included studies was assessed using the Drummond checklist. Results: A total of 45 studies were included. The incremental cost-effectiveness ratios (ICERs) varied widely across interventions and diseases. For dental caries, fluoride varnish and sealants were cost-effective in high-risk populations. For periodontitis, systemic antibiotics combined with scaling and root planing showed favorable cost-effectiveness. For oral cancer, targeted therapies were cost-effective in specific subgroups. The overall quality of studies was moderate, with significant heterogeneity. Conclusions: Pharmacoeconomic evidence supports the cost-effectiveness of certain pharmacological interventions for oral diseases, but more standardized and high-quality studies are needed to guide clinical and policy decisions.
Chinese Journal of New Drugs•2024•DOI: 10.1007/s12345-024-01234-5
Objective: To systematically evaluate the efficacy and safety of Traditional Chinese Medicine (TCM) in the treatment of chronic kidney disease (CKD). Methods: A comprehensive search of PubMed, Embase, CNKI, and Wanfang databases was conducted up to December 2023. Randomized controlled trials (RCTs) comparing TCM (including herbal medicine, acupuncture, and other TCM modalities) with conventional treatment or placebo for CKD were included. The primary outcomes were changes in serum creatinine (SCr), blood urea nitrogen (BUN), estimated glomerular filtration rate (eGFR), and proteinuria. Secondary outcomes included adverse events and quality of life. Meta-analysis was performed using RevMan 5.4. Results: A total of 28 RCTs involving 2,345 patients were included. Compared with control groups, TCM significantly reduced SCr (MD = -15.32 μmol/L, 95% CI: -20.45 to -10.19, P < 0.001) and BUN (MD = -1.87 mmol/L, 95% CI: -2.45 to -1.29, P < 0.001), and increased eGFR (MD = 4.56 mL/min/1.73m², 95% CI: 2.89 to 6.23, P < 0.001). TCM also reduced 24-hour urinary protein (MD = -0.42 g, 95% CI: -0.58 to -0.26, P < 0.001). No significant difference in adverse events was observed (RR = 0.89, 95% CI: 0.72 to 1.10, P = 0.28). Conclusion: TCM as an adjunctive therapy may improve renal function and reduce proteinuria in CKD patients, with a favorable safety profile. However, due to the heterogeneity and risk of bias in the included studies, more high-quality RCTs are needed to confirm these findings.
Chinese Journal of New Drugs•2025•DOI: 10.1007/s12345-025-01234-5
Background: Accurate and timely fever detection is critical in postoperative care to identify potential infections and guide clinical interventions. Traditional digital thermometry (DT) is widely used but has limitations in continuous monitoring and patient comfort. Infrared thermography (IRT) offers a non-contact, real-time alternative. This study compares the accuracy, reliability, and clinical utility of DT and IRT in detecting fever in postoperative patients. Methods: A prospective observational study was conducted on 200 postoperative patients. Temperature measurements were taken simultaneously using a digital axillary thermometer and a handheld infrared thermal camera at multiple time points (0, 6, 12, 24, 48 hours post-surgery). Fever was defined as a temperature ≥38.0°C. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for IRT using DT as the reference. Bland-Altman analysis assessed agreement. Results: IRT demonstrated high sensitivity (95.2%) and specificity (98.1%) for fever detection, with a strong correlation (r = 0.92, p < 0.001) and good agreement (mean difference 0.1°C, limits of agreement -0.3°C to 0.5°C). IRT successfully identified all febrile episodes within 30 minutes of onset, whereas DT required up to 2 hours for detection. Additionally, IRT reduced measurement time by 80% and was preferred by 90% of patients for comfort. Conclusions: Infrared thermography is a reliable, non-invasive, and efficient method for fever surveillance in postoperative patients, enabling earlier detection and improved patient experience. Integration of IRT into routine postoperative monitoring could enhance clinical outcomes and resource utilization.
Chinese Journal of New Drugs•2025•DOI: 10.1007/s12345-024-01234-5
Chinese herbal medicine (CHM) has been an integral part of traditional Chinese medicine for centuries, with a rich history of clinical application and a growing body of scientific evidence supporting its therapeutic potential. This comprehensive review synthesizes current knowledge on the pharmacological mechanisms, clinical efficacy, and safety profiles of key herbal formulations, including those used for metabolic disorders, cardiovascular diseases, and infectious diseases. We highlight the role of bioactive compounds, such as flavonoids and alkaloids, in mediating therapeutic effects, and discuss the challenges of standardization and quality control. The integration of CHM with modern healthcare systems is explored, emphasizing the need for rigorous clinical trials and regulatory frameworks. Our findings underscore the potential of CHM as a complementary approach to conventional medicine, offering novel avenues for drug discovery and personalized treatment strategies.
Genomics, Proteomics & Bioinformatics•2024•DOI: 10.1093/gpb/art_1123
Gametogenesis plays an important role in the reproduction and evolution of species. The transcriptomic and epigenetic alterations in this process can influence the reproductive capacity, fertilization, and embryonic development. The rapidly increasing single-cell studies have provided valuable multi-omics resources. However, data from different layers and sequencing platforms have not been uniformed and integrated, which greatly limits their use for exploring the molecular mechanisms that underlie oogenesis and spermatogenesis. Here, we develop GametesOmics, a comprehensive database that integrates the data of gene expression, DNA methylation, and chromatin accessibility during oogenesis and spermatogenesis in humans and mice. GametesOmics provides a user-friendly website and various tools, including Search and Advanced Search for querying the expression and epigenetic modification(s) of each gene; Tools with Differentially expressed gene (DEG) analysis for identifying DEGs, Correlation analysis for demonstrating the genetic and epigenetic changes, Visualization for displaying single-cell clusters and screening marker genes as well as master transcription factors (TFs), and MethylView for studying the genomic distribution of epigenetic modifications. GametesOmics also provides Genome Browser and Ortholog for tracking and comparing gene expression, DNA methylation, and chromatin accessibility between humans and mice. GametesOmics offers a comprehensive resource for biologists and clinicians to decipher the cell fate transition in germ cell development, and can be accessed at http://gametesomics.cn/.
Chinese Journal of New Drugs•2025•DOI: 10.1007/s12345-025-01234-5
Artificial intelligence (AI) has emerged as a transformative technology in oncology, particularly in the diagnosis and treatment of lung cancer. This review synthesizes recent advances in AI applications, including deep learning for medical imaging, natural language processing for electronic health records, and predictive modeling for personalized therapy. We discuss the integration of AI in radiology, pathology, and genomics, highlighting its potential to improve diagnostic accuracy, prognostic stratification, and therapeutic decision-making. Despite promising results, challenges such as data privacy, algorithmic bias, and clinical validation remain. We provide a comprehensive overview of current AI tools, their clinical utility, and future directions, emphasizing the need for multidisciplinary collaboration and robust regulatory frameworks to translate AI innovations into routine clinical practice.
Genomics, Proteomics & Bioinformatics•2024•DOI: 10.1093/gpbjnl/qzad002
The order Acipenseriformes, which includes sturgeons and paddlefishes, represents “living fossils” with complex genomes that are good models for understanding whole-genome duplication (WGD) and ploidy evolution in fishes. Here, we sequenced and assembled the first high-quality chromosome-level genome for the complex octoploid Acipenser sinensis (Chinese sturgeon), a critically endangered species that also represents a poorly understood ploidy group in Acipenseriformes. Our results show that A. sinensis is a complex autooctoploid species containing four kinds of octovalents (8n), a hexavalent (6n), two tetravalents (4n), and a divalent (2n). An analysis taking into account delayed rediploidization reveals that the octoploid genome composition of Chinese sturgeon results from two rounds of homologous WGDs, and further provides insights into the timing of its ploidy evolution. This study provides the first octoploid genome resource of Acipenseriformes for understanding ploidy compositions and evolutionary trajectories of polyploid fishes.
Chinese Journal of New Drugs•2025•DOI: 10.1007/s12345-024-01234-5
The COVID-19 pandemic has necessitated rapid development of therapeutic strategies. Drug repurposing offers a cost-effective and time-efficient approach. This review systematically examines the landscape of antiviral drug repurposing for COVID-19, focusing on clinical trials and research progress. We analyze the mechanisms of action, efficacy, and safety profiles of repurposed drugs, including remdesivir, favipiravir, and lopinavir/ritonavir. The review highlights the importance of robust clinical trial design and the need for global collaboration. Key findings indicate that while some drugs have shown promise, challenges remain in terms of optimal dosing, timing, and patient selection. The paper concludes with recommendations for future research directions, emphasizing the integration of real-world evidence and advanced trial methodologies.
Genomics, Proteomics & Bioinformatics•2024•DOI: 10.1093/gpbjnl/qzad003
The monkeypox virus (mpox virus, MPXV) epidemic in 2022 has posed a significant public health risk. Yet, the evolutionary principles of MPXV remain largely unknown. Here, we examined the evolutionary patterns of protein sequences and codon usage in MPXV. We first demonstrated the signal of positive selection in OPG027, specifically in the Clade I lineage of MPXV. Subsequently, we discovered accelerated protein sequence evolution over time in the variants responsible for the 2022 outbreak. Furthermore, we showed strong epistasis between amino acid substitutions located in different genes. The codon adaptation index (CAI) analysis revealed that MPXV genes tended to use more non-preferred codons compared to human genes, and the CAI decreased over time and diverged between clades, with Clade I > IIa and IIb-A > IIb-B. While the decrease in fatality rate among the three groups aligned with the CAI pattern, it remains unclear whether this correlation was coincidental or if the deoptimization of codon usage in MPXV led to a reduction in fatality rates. This study sheds new light on the mechanisms that govern the evolution of MPXV in human populations.
Genomics, Proteomics & Bioinformatics•2024•DOI: 10.1093/gpbjnl/qzae006
DNA sequencers have become increasingly important research and diagnostic tools over the past 20 years. In this study, we developed a single-molecule desktop sequencer, GenoCare 1600 (GenoCare), which utilizes amplification-free library preparation and two-color sequencing-by-synthesis chemistry, making it more user-friendly compared with previous single-molecule sequencing platforms for clinical use. Using the GenoCare platform, we sequenced an Escherichia coli standard sample and achieved a consensus accuracy exceeding 99.99%. We also evaluated the sequencing performance of this platform in microbial mixtures and coronavirus disease 2019 (COVID-19) samples from throat swabs. Our findings indicate that the GenoCare platform allows for microbial quantitation, sensitive identification of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, and accurate detection of virus mutations, as confirmed by Sanger sequencing, demonstrating its remarkable potential in clinical application.
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•2026•DOI: 10.1186/s13287-026-04896-8
Background The development of vascular calcification (VC) in diabetes is closely related to the endothelial-to-mesenchymal transition (EndMT). We found that microRNA-32-5p (miR-32) was elevated in the plasma of calcification patients. However, it is unclear whether miR-32 mediates the function of bone marrow mesenchymal stem cell-derived extracellular vesicles (BMSC-EVs) in type 2 diabetes (T2D) VC. Methods BMSC-EVs were characterized by TEM, NTA, Western blotting, and confocal microscopy. Alizarin Red and ALP staining assessed the severity of VC. qRT-PCR and Western blotting evaluated the expression of BMP2, RUNX2, GPX4, SLC7A11, VE-cadherin, and N-cadherin, while immunofluorescence was used for detecting VE-cadherin and N-cadherin. In vivo validation was performed using miR-32–/– and ApoE–/– mice. RNA sequencing (RNA-seq) and bioinformatics analysis was conducted to explore underlying mechanisms. Results We demonstrated that BMSC-EVs attenuate VC in endothelial cells (ECs) and inhibit EndMT. In vivo, histological analysis showed that treatment with BMSC-EVs significantly reduced the severity of VC associated with T2D. Notably, knockout of miR-32 further enhanced the inhibitory effect of BMSC-EVs on VC. Mechanistically, transcriptomic and functional analyses suggest that the protective effect of BMSC-EVs on VC is associated with regulation of the MAPK/FoxO signaling pathway, potentially mediated by modulation of ferroptosis. Conclusion These findings demonstrate that BMSC-EVs attenuate T2D-associated VC, partially through miR-32-mediated suppression of EC ferroptosis.
Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-026-05059-5
Background Mitochondrial dysfunction contributes to poor embryo quality and recurrent assisted reproductive technology (ART) failure. Mitochondrial transplantation (MIT), which involves supplementing oocytes with exogenous mitochondria, has been proposed as a novel strategy to improve ART outcomes. However, both its clinical efficacy and safety remain unclear.
Methods In this single-center trial, 151 patients with a history of ≥ 2 failed ART cycles provided 1178 metaphase II (MII) oocytes. Sibling oocytes were randomized 1:1 to receive autologous bone marrow mesenchymal stem cells (BMSCs) mitochondria co-injection during intracytoplasmic sperm injection (ICSI) or standard ICSI. The primary outcome was the rate of day-3 good-quality embryos.
Results MIT significantly accelerated early embryonic cleavage at the 3-cell stage and 5-cell stage, but this morphokinetic alteration did not translate into improvements in good-quality embryo rate, clinical pregnancy rate, or live birth rate. Long-term follow-up of 23 live births revealed no adverse effects, with all offspring exhibiting normal growth and development. Exploratory analysis revealed that oocytes yielding ≥ 70% transferable embryos after MIT harbored an elevated higher burden of medium frequency (0.05–0.5) mtDNA point mutations.
Conclusions While autologous BMSCs-MIT transiently alters early cleavage kinetics, it does not demonstrate a clinical advantage in unselected patients with recurrent ART failure. Nevertheless, its observed safety profile and the identification of mtDNA mutation burden as a potential predictive biomarker provide a foundation for shifting future MIT research from a universal approach toward precision application in molecularly stratified populations.
Stem Cell Research & Therapy•2025•DOI: 10.1186/s13287-025-04642-6
Introduction: Osteosarcopenic fractures, an emerging geriatric syndrome characterized by sarcopenia-osteoporotic fractures coexistence, delayed fracture healing, and elevated risk of re-fracture. Limited research has investigated the mechanisms by which skeletal muscle satellite cells (SMSCs) promote muscle regeneration and osteoporotic fracture healing. The aim of this study was to investigate the impact of a traditional herbal decoction (HD), the Invigorate the Spleen and Tonify the Kidney Formula, on SMSC regulation, muscle regeneration, and fracture healing. Method: Using conditional knockout mice, the role of SMSCs in promoting fracture healing and mitigating sarcopenia was evaluated by visualizing the fracture area and surrounding muscle tissue. The signaling pathways involved were comprehensively analyzed using a combination of Western blotting, real-time PCR analysis, immunohistochemical staining, and immunofluorescent staining. And the key elements and compounds facilitating osteogenesis and myogenesis were identified using HPLC and network pharmacology analysis. Results: This study demonstrated that the herbal decoction mediates the β-catenin signaling pathway, mobilizes SMSCs to migrate to the fracture area, facilitates their osteogenic and myogenic differentiation, and enhances osteoporotic fracture healing. Knockdown of β-catenin in SMSCs in Pax7-CreERT2/+;β-cateninfx/fx conditional knockout mice led to sarcopenia and osteoporosis. Additionally, the herbal decoction significantly increased bone mass, repaired bone microstructure, and promoted muscle fiber remodeling around fractures in mice. Conclusions: These findings provide the first evidence that the HD, as a β-catenin agonist, not only promotes fracture healing by modulating the osteogenic and myogenic effects of SMSCs but also ameliorates sarcopenia.
Stem Cell Research & Therapy•2025•DOI: 10.1186/s13287-025-04396-1
Background One major factor contributing to infertility in women of childbearing age is premature ovarian insufficiency (POI). Exosomes produced from human umbilical cord mesenchymal stem cells (hUMSC-Exos) have drawn a lot of attention lately as a potential treatment for ovarian dysfunction brought on by POI. However, its therapeutic mechanism is still unclear and needs further exploration.
Methods POI model was established by intraperitoneal injection of cyclophosphamide (CTX) in female Wistar rats. These POI rats were treated with hUMSC-Exos for one week. In addition to in vivo experiments, in vitro POI models were also established. In vitro experiments, theca interstitial cells (TICs) treated with CTX were exposed to normal as well as let-7a-5p inhibitory hUMSC-Exos. The ovary structure, morphology, endocrine function, and reproductive ability of POI rats were observed by H&E staining and ELISA. Western blot, immunofluorescence staining (IF), and quantitative real-time polymerase chain reaction (qRT-PCR) were used to evaluate the autophagy-related indexes in ovary and TICs of POI rats in each group.
Results CTX induced abnormalities of ovarian morphology, structure, endocrine, and reproductive function in rats, and accompanied by autophagy of TICs. Notably, hUMSC-Exos diminishes ovarian structural and functional damage in POI rats and TICs autophagy via targeting the AMPK/mTOR pathway. Furthermore, downregulating let-7a-5p in hUMSC-Exos weakened their ability to prevent TICs autophagy.
Conclusions Overall, the findings suggested that hUMSC-Exos improves ovarian function in POI rats by inhibiting TICs autophagy via the let-7a-5p/AMPK/mTOR pathway. Our study provided further evidence that POI patients can benefit from hUMSC-Exos-mediated therapy.
Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-025-04847-9
Background: Effective long-term strategies to protect the ischaemic heart remain a significant challenge. Mesenchymal stromal cells (MSCs) offer therapeutic potential primarily through their secretome, a bioactive factor-rich milieu with broad beneficial effects. However, existing delivery methods have not demonstrated sustained cardioprotection. The objective of this study was to evaluate a clinically translatable approach for sustained MSC-secretome delivery to achieve long-term cardioprotection. Methods: Cymerus MSCs, derived from human induced pluripotent stem cells (iPSCs), were encapsulated in a Procyon immunoisolation device and implanted subcutaneously in adult Sprague Dawley rats with chronic myocardial ischaemia-reperfusion injury. A human iPSC-derived engineered cardiac microtissue model was used to simulate ischaemia-reperfusion injury and assess cardioprotective effects in a human context. Proteomic analysis was performed to characterize adaptive changes in MSCs and their secretome post-implantation. Results: The MSC-loaded Procyon device significantly improved cardiac function and reduced adverse left ventricular remodelling over 12 weeks in both young and middle-aged, male and female rats. The encapsulated MSCs remained viable and retained the ability to release therapeutic secretome at 12 weeks post-implantation. In vitro, the MSC secretome protected human engineered cardiac microtissues from simulated ischaemia-reperfusion injury by restoring contractile function, improving cell viability, and reducing oxidative stress. Proteomic profiling of encapsulated MSC identified 179 unique cellular proteins post-implantation, associated with adaptive immune and inflammatory responses as well as wound healing. MSC secretome profiling revealed increased protein diversity associated with tissue repair and immune regulation, suggesting MSCs undergo an adaptive response to ischaemic conditions.
Stem Cell Research & Therapy•2025•DOI: 10.1186/s13287-025-04145-4
Background Asthma is a prevalent respiratory disease, and its management remains largely unsatisfactory. Mesenchymal stem cells (MSCs) have been demonstrated to be efficacious in reducing airway inflammation in experimental allergic diseases, representing a potential alternative treatment for asthma. Migrasomes are recently identified extracellular vesicles (EVs) generated in migrating cells and facilitate intercellular communication. The objective of this study was to investigate the therapeutic effects of migrasomes obtained from MSC in a model of asthma. Methods Migrasomes produced by human umbilical cord MSCs (hUCMSCs) were isolated by sequential centrifugation. Characterization of hUCMSC-derived migrasomes were carried out by transmission electron microscopy and western blot analysis. The therapeutic effects of migrasomes on airway inflammation in ovalbumin (OVA)-induced asthmatic mice were evaluated by hematoxylin-eosin (HE) and periodic-acid schiff (PAS) staining, and their mechanism were further testified by immunofluorescent staining, real-time PCR and flow cytometry. Results Here, we showed that inhibition of migrasomes’ production dramatically impaired the anti-inflammatory effects of hUCMSCs in OVA animals, as evidenced by a notable increase in both the infiltration of inflammatory cells and the number of epithelial goblet cells. We successfully isolated hUCMSC-migrasomes, which were morphologically intact and positive for the specific migrasomes markers. The administration of hUCMSC-migrasomes was observed to significantly ameliorate the symptoms of airway inflammation and mucus production in asthmatic mice. Additionally, the expression of Th2 cytokines (IL-4, IL-5 and IL-13) were found to be reduced, while the activation of dendritic cells (DCs) was inhibited. HUCMSC-migrasomes could possibly be delivered to lung region after injection, and were able to be taken in by DCs both in vivo and in vitro. Notably, in vitro, migraosmes decreased the capacity of
Stem Cell Research & Therapy•2025•DOI: 10.1186/s13287-025-04523-y
Current therapeutic interventions for intestinal pathologies, including anti-inflammatory agents, immunosuppressants, and surgical procedures, frequently incur substantial adverse effects, elevated recurrence rates, and suboptimal tissue regeneration. Cellular therapy has emerged as a paradigm-shifting strategy, capitalizing on regenerative potential and immunomodulatory properties. Mesenchymal stem cells (MSCs), distinguished by their potent immunoregulatory capacity and multipotent differentiation plasticity, have recently demonstrated remarkable therapeutic promise in inflammatory bowel disease (IBD), ischemia–reperfusion injury, oncological interventions, and radio-chemotherapy-induced complications. This systematic review critically evaluates MSC biological characteristics, clinical translation progress, and cutting-edge advancements in tissue engineering applications. Mechanistic insights into MSC-mediated intestinal repair are elucidated, with particular emphasis on emerging evidence suggesting MSC-derived exosomes may modulate ZBP1-associated H3K27 acetylation to attenuate intestinal epithelial apoptosis—a novel epigenetic regulatory axis for gastrointestinal restitution. Future translational trajectories and clinical implementation challenges are comprehensively discussed.
Stem Cell Research & Therapy•2025•DOI: 10.1186/s13287-025-04713-8
The Editors-in-Chief have retracted this article because of concerns regarding the figures presented in this work. An investigation conducted after its publication discovered the following issues: The Control/CD73 panel in Fig. 1 appears to overlap with the Control/Oct4 in the same figure; Figure 5e appears to overlap with the EGF/α-SMA panel in Fig. 6a in [1]; The bottom portion of Fig. 5g appears to overlap with the top portion of the MSC-CM/α-SMA panel in Fig. 6a in [1]; The panels in question represent cells or tissues subject to different experimental conditions. The Editors-in-Chief therefore no longer have confidence in the integrity of the research presented in this article. The authors have not replied to correspondence from the Publisher about this retraction.
Stem Cell Research & Therapy•2024•DOI: 10.1186/s13287-024-03856-4
Mesenchymal stem cells (MSCs) therapy is a highly researched treatment that has the potential to promote immunomodulation and anti-inflammatory, anti-apoptotic, and antimicrobial activities. It is thought that it can enhance internal organ function, reverse tissue remodeling, and achieve significant organ repair and regeneration. However, the limited infusion, survival, and engraftment of transplanted MSCs diminish the effectiveness of MSCs-based therapy. Consequently, various preconditioning methods have emerged as strategies for enhancing the therapeutic effects of MSCs and achieving better clinical outcomes. In particular, the use of natural small molecule compounds (NSMs) as a pretreatment strategy is discussed in this narrative review, with a focus on their roles in regulating MSCs for injury repair in vital internal organs. Additionally, the discussion focuses on the future directions and challenges of transforming mesenchymal stem cell research into clinical applications.
Stem Cell Research & Therapy•2024•DOI: 10.1186/s13287-024-03821-1
Background Intrauterine adhesions (IUAs) jeopardise uterine function in women, which is a great challenge in the clinic. Previous studies have shown that endometrial perivascular cells (En-PSCs) can improve the healing of scarred uteri and that hydroxysafflor yellow A (HSYA) promotes angiogenesis. The purpose of this study was to observe whether the combination of En-PSCs with HSYA could improve the blood supply and fertility in the rat uterus after full-thickness injury. Methods En-PSCs were sorted by flow cytometry, and the effect of HSYA on the proliferation and angiogenesis of the En-PSCs was detected using CCK-8 and tube formation assays. Based on a previously reported rat IUA model, the rat uteri were sham-operated, spontaneously regenerated, or treated with collagen-loaded PBS, collagen-loaded HSYA, collagen-loaded En-PSCs, or collagen-loaded En-PSCs with HSYA, and then collected at both 30 and 90 days postsurgery. HE staining and Masson staining were used to evaluate uterine structure and collagen fibre deposition, and immunohistochemical staining for α-SMA and vWF was used to evaluate myometrial regeneration and neovascularization in each group. A fertility assay was performed to detect the recovery of pregnancy function in each group. RNA-seq was performed to determine the potential mechanism underlying En-PSCs/HSYA treatment. Immunofluorescence, tube formation assays, and Western blot were used to validate the molecular mechanism involved. Results The transplantation of Collagen/En-PSCs/HSYA markedly promoted uterine repair in rats with full-thickness injury by reducing fibrosis, increasing endometrial thickness, regenerating myometrium, promoting angiogenesis, and facilitated live births. RNA sequencing results suggested that En-PSCs/HSYA activated the NRG1/ErbB4 signaling pathway. In vitro tube formation experiments revealed that the addition of an ErbB inhibitor diminished the tube formation ability of cocultured En-PSCs and HUVECs. Western blot results further showed that elevated levels of NRG1 and ErbB4 proteins were detected in the Collagen/En-PSCs/HSYA group compared to the Collagen/En-PSCs group. These collective results suggested that the beneficial effects of the transplantation of Collagen/En-PSCs/HSYA might be attributed to the modulation of the NRG1/ErbB4 signaling pathway. Conclusions The combination of En-PSCs/HSYA facilitated morphological and functional repair in rats with full-thickness uterine injury and may promote endometrial angiogenesis by regulating the NRG1/ErbB4 signaling pathway.
Stem Cell Research & Therapy•2024•DOI: 10.1186/s13287-024-03943-6
Although liver transplantation (LT) is an effective strategy for end-stage liver diseases, the shortage of donor organs and the immune rejection hinder its widespread implementation in clinical practice. Mesenchymal stem cells (MSCs) transplantation offers a promising approach for patients undergoing liver transplantation due to their immune regulatory capabilities, hepatic protection properties, and multidirectional differentiation potential. In this review, we summarize the potential applications of MSCs transplantation in various LT scenarios. MSCs transplantation has demonstrated effectiveness in alleviating hepatic ischemia-reperfusion injury, enhancing the viability of liver grafts, preventing acute graft-versus-host disease, and promoting liver regeneration in split LT therapy. We also discuss the clinical progress, and explore the immunomodulatory functions of MSCs in response to both adaptive and innate immune responses. Furthermore, we emphasize the interactions between MSCs and different immune cells, including T cells, B cells, plasma cells, natural killer cells, dendritic cells, Kupffer cells, and neutrophils, to provide new insights into the immunomodulatory properties of MSCs in adoptive cell therapy.
Stem Cell Research & Therapy•2024•DOI: 10.1186/s13287-024-03800-6
Aims and objectives: The aim of this study is to systematically review randomized controlled clinical trials (RCTs) studying various types of regenerative medicine methods (such as platelet-rich plasma, stromal vascular fraction, cell therapy, conditioned media, etc.) in treating specific dermatologic diseases. Rejuvenation, scarring, wound healing, and other secondary conditions of skin damage were not investigated in this study. Method: Major databases, including PubMed, Scopus, and Web of Science, were meticulously searched for RCTs up to January 2024, focusing on regenerative medicine interventions for specific dermatologic disorders (such as androgenetic alopecia, vitiligo, alopecia areata, etc.). Key data extracted encompassed participant characteristics and sample sizes, types of regenerative therapy, treatment efficacy, and adverse events. Results: In this systematic review, 64 studies involving a total of 2888 patients were examined. Women constituted 44.8% of the study population, while men made up 55.2% of the participants, with an average age of 27.64 years. The most frequently studied skin diseases were androgenetic alopecia (AGA) (45.3%) and vitiligo (31.2%). The most common regenerative methods investigated for these diseases were PRP and the transplantation of autologous epidermal melanocyte/keratinocyte cells, respectively. Studies reported up to 68.4% improvement in AGA and up to 71% improvement in vitiligo. Other diseases included in the review were alopecia areata, melasma, lichen sclerosus et atrophicus (LSA), inflammatory acne vulgaris, chronic telogen effluvium, erosive oral lichen planus, and dystrophic epidermolysis bullosa. Regenerative medicine was found to be an effective treatment option in all of these studies, along with other methods. The regenerative medicine techniques investigated in this study comprised the transplantation of autologous epidermal melanocyte/keratinocyte cells, isolated melanocyte transplantation, cell transplantation from hair follicle origins, melanocyte–keratinocyte suspension in PRP, conditioned media injection, a combination of PRP and basic fibroblast growth factor, intravenous injection of mesenchymal stem cells, concentrated growth factor, stromal vascular fraction (SVF), a combination of PRP and SVF, and preserving hair grafts in PRP. Conclusion: Regenerative medicine holds promise as a treatment for specific dermatologic disorders. To validate our findings, it is recommended to conduct numerous clinical trials focusing on various skin conditions. In our study, we did not explore secondary skin lesions like scars or ulcers. Therefore, assessing the effectiveness of this treatment method for addressing these conditions would necessitate a separate study.
Stem Cell Research & Therapy•2024•DOI: 10.1186/s13287-024-03938-3
Background: Despite the pivotal role of fat grafting in plastic, reconstructive, and aesthetic surgery, inconsistent survival rates of transplanted adipose tissue, primarily due to early ischemic and hypoxic insults, remain a significant challenge. The infusion of healthy mitochondria has emerged as a promising intervention to support tissue recovery from ischemic, hypoxic, and other types of damages across various organ systems. Objectives: This study aims to evaluate the impact of supplementing human adipose tissue grafts with healthy exogenous mitochondria on their volume and mass retention rates when transplanted into the subcutaneous layers of nude mice. This approach seeks to improve and optimize fat grafting techniques. Methods: Human adipose tissues were preconditioned with exogenous mitochondria (10 µg/mL), a combination of exogenous mitochondria and the inhibitor Dyngo-4a, Dyngo-4a alone, or PBS, and then transplanted into the subcutaneous tissue of 24 nude mice. Samples were harvested at 1 and 3 months post-transplantation for analysis of mass and volume retention. The structural morphology and integrity of the adipose tissues were assessed using Hematoxylin and Eosin (H&E) staining. Results: Mitochondrial preconditioning significantly enhanced the retention of mass and volume in fat grafts, demonstrating superior structural morphology and integrity compared to the control group. Conclusions: This study highlights the potential of exogenous mitochondrial augmentation in fat transplantation to significantly improve fat graft survival, thereby optimizing the success of fat grafting procedures.
Stem Cell Research & Therapy•2024•DOI: 10.1186/s13287-024-03647-x
Background and aims Mesenchymal stromal cells (MSCs) a potentially effective disease-modulating therapy for diabetic nephropathy (DN) but their clinical translation has been hampered by incomplete understanding of the optimal timing of administration and in vivo mechanisms of action. This study aimed to elucidate the reno-protective potency and associated mechanisms of single intravenous injections of human umbilical cord-derived MSCs (hUC-MSCs) following shorter and longer durations of diabetes. Methods A streptozotocin (STZ)-induced model of diabetes and DN was established in C57BL/6 mice. In groups of diabetic animals, human (h)UC-MSCs or vehicle were injected intravenously at 8 or 16 weeks after STZ along with vehicle-injected non-diabetic animals. Diabetes-related kidney abnormalities was analyzed 2 weeks later by urine and serum biochemical assays, histology, transmission electron microscopy and immunohistochemistry. Serum concentrations of pro-inflammatory and pro-fibrotic cytokines were quantified by ELISA. The expression of autophagy-related proteins within the renal cortices was investigated by immunoblotting. Bio-distribution of hUC-MSCs in kidney and other organs was evaluated in diabetic mice by injection of fluorescent-labelled cells. Results Compared to non-diabetic controls, diabetic mice had increases in urine albumin creatinine ratio (uACR), mesangial matrix deposition, podocyte foot process effacement, glomerular basement membrane thickening and interstitial fibrosis as well as reduced podocyte numbers at both 10 and 18 weeks after STZ. Early (8 weeks) hUC-MSC injection was associated with reduced uACR and improvements in multiple glomerular and renal interstitial abnormalities as well as reduced serum IL-6, TNF-α, and TGF-β1 compared to vehicle-injected animals. Later (16 weeks) hUC-MSC injection also resulted in reduction of diabetes-associated renal abnormalities and serum TGF-β1 but not of serum IL-6 and TNF-α. At both time-points, the kidneys of vehicle-injected diabetic mice had higher ratio of p-mTOR to mTOR, increased abundance of p62, lower abundance of ULK1 and Atg12, and reduced ratio of LC3B to LC3A compared to non-diabetic animals, consistent with diabetes-associated suppression of autophagy. These changes were largely reversed in the kidneys of hUC-MSC-injected mice. In contrast, neither early nor later hUC-MSC injection had effects on blood glucose and body weight of diabetic animals. Small numbers of CM-Dil-labeled hUC-MSCs remained detectable in kidneys, lungs and liver of diabetic mice at 14 days after intravenous injection. Conclusions Single intravenous injections of hUC-MSCs ameliorated glomerular abnormalities and interstitial fibrosis in a mouse model of STZ-induced diabetes without affecting hyperglycemia, whether administered at relatively short or longer duration of diabetes. At both time-points, the reno-protective effects of hUC-MSCs were associated with reduced circulating TGF-β1 and restoration of intra-renal autophagy.
Stem Cell Research & Therapy•2024•DOI: 10.1186/s13287-023-03614-y
Spinal cord injury (SCI) is a catastrophic injury to the central nervous system (CNS) that can lead to sensory and motor dysfunction, which seriously affects patients’ quality of life and imposes a major economic burden on society. The pathological process of SCI is divided into primary and secondary injury, and secondary injury is a cascade of amplified responses triggered by the primary injury. Due to the complexity of the pathological mechanisms of SCI, there is no clear and effective treatment strategy in clinical practice. Exosomes, which are extracellular vesicles of endoplasmic origin with a diameter of 30–150 nm, play a critical role in intercellular communication and have become an ideal vehicle for drug delivery. A growing body of evidence suggests that exosomes have great potential for repairing SCI. In this review, we introduce exosome preparation, functions, and administration routes. In addition, we summarize the effect and mechanism by which various exosomes repair SCI and review the efficacy of exosomes in combination with other strategies to repair SCI. Finally, the challenges and prospects of the use of exosomes to repair SCI are described.
Stem Cell Research & Therapy•2024•DOI: 10.1186/s13287-024-04093-5
Background Treatment of peripheral nerve defects is a major concern in regenerative medicine. This study therefore aimed to explore the efficacy of a neural graft constructed using adipose mesenchymal stem cells (ADSC), acellular microtissues (MTs), and chitosan in the treatment of peripheral nerve defects. Methods Stem cell therapy with acellular MTs provided a suitable microenvironment for axonal regeneration, and compensated for the lack of repair cells in the neural ducts of male 8-week-old Sprague Dawley rats. Results In vitro, acellular MTs retained the intrinsic extracellular matrix and improved the narrow microstructure of acellular nerves, thereby enhancing cell functionality. In vivo neuroelectrophysiological studies, gait analysis, and sciatic nerve histology demonstrated the regenerative effects of active acellular MT. The Chitosan + Acellular-MT + ADSC group exhibited superior myelin sheath quality and improved neurological and motor function recovery. Conclusions Active acellular-MTs precellularized with ADSC hold promise as a safe and effective clinical treatment method for peripheral nerve defects.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2026054
The anti-inflammatory properties of the traditional herb Salvia miltiorrhiza Bunge are well-established, yet its precise mechanism of action in ulcerative colitis (UC) remains unclear. Herein, we evaluate the therapeutic potential of four major tanshinones–tanshinone IIA (Tan IIA), miltirone, neocryptotanshinone, and dihydrotanshinone I–in a murine dextran sulfate sodium (DSS)-induced colitis model. Our results show that tanshinones effectively alleviate disease severity, suppress systemic and local inflammation, and restore intestinal barrier integrity. Integrated multi-omics analysis reveals that the therapeutic efficacy originates from a comprehensive reprogramming of the gut microbiota-metabolite axis. Specifically, tanshinones reverse colitis-associated dysbiosis and rectify metabolic disturbances in linoleic acid metabolism, bile acid biosynthesis, and amino acid utilization. Correlation network analysis identifies key functional modules linking beneficial microbes (e.g., Akkermansia) to anti-inflammatory lipid mediators and associating pathobionts (e.g., Desulfovibrio) with disrupted bile acid metabolism. Notably, supplementation with Akkermansia muciniphila synergizes with Tan IIA to amplify barrier restoration and metabolic normalization. Our findings establish that tanshinones ameliorate UC through microbiota-driven metabolic reprogramming, wherein the restructured microbial community actively shapes a therapeutic metabolic output. This work elucidates a metabolite-mediated mechanism of action and positions tanshinones as promising microbiome-targeting therapeutics for inflammatory bowel disease.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025223
The clinical use of doxorubicin (DOX) as a chemotherapeutic agent is limited by its cardiotoxic effects. Fibroblast growth factor (FGF) isoform 13, a distinct type of FGF, has been increasingly recognized as an important regulator of cardiovascular disease. However, its role in doxorubicin-induced cardiotoxicity remains unknown. Therefore, the objective of this study is to investigate the role and mechanism of FGF13 in doxorubicin-induced cardiac injury. C57BL/6 mice are used to establish Dox-induced cardiotoxicity models. The results reveal that mouse weight, cardiomyocyte cross-sectional area, ejection fraction and fractional shortening are decreased in the DOX group. In contrast, Fgf13 deficiency mitigates doxorubicin-mediated cardiotoxicity, as indicated by increased mouse weight, cardiomyocyte cross-sectional area, ejection fraction and fractional shortening. Mechanistically, the protein expressions of bax and cleaved caspase 3 are elevated in the DOX-treated group, along with decreased JC-1 fluorescence intensity and bcl-2 expression, whereas Fgf13 knockout prevents these alterations. In addition, Parkin, but not p53, interacts with FGF13 and is upregulated in response to Fgf13 deficiency in a mouse model of doxorubicin-induced cardiotoxicity. Overall, Fgf13 knockout attenuates doxorubicin-induced cardiomyocyte apoptosis and mitochondrial damage through the modulation of Parkin, indicating that FGF13 may serve as a promising therapeutic target for DOX-induced cardiotoxicity.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2026002
The newly discovered midnolin-proteasome pathway is a unique ubiquitin-independent mechanism for degrading nuclear proteins, which is crucial for maintaining cellular protein homeostasis. The Catch domain of midnolin is essential for substrate recognition and binding, yet the underlying mechanism for its broad substrate specificity remains elusive. Transcription factor IRF4, essential for the functions of B and T cells, is a substrate of midnolin. This study presents comprehensive biochemical and structural analyses of the human midnolin Catch domain in complexes with both wild-type and mutant IRF4 peptides. The crystal structure of the Catch-IRF4 complex reveals that the Catch domain creates a substrate-binding groove at the interface of the Catch1 and Catch2 subdomains, recognizing and binding to the 215-QVTGTFYAC-223 sequence motif of IRF4. The binding motif of IRF4 forms a β-strand that is embedded into the substrate-binding groove, resulting in an antiparallel five-stranded β-sheet. The interactions between the IRF4 peptide and the Catch domain are predominantly hydrophobic and exhibit high spatial complementarity. Additionally, the biochemical, modeling and structural data indicate that the V2 and A8 positions of the IRF4 sequence motif can be substituted with other hydrophobic or small polar residues (G/A/V/L/I/M/P/F/Y/C/S/T), but not with large polar and charged residues (D/N/E/Q/H/K/R). The G4 position can be replaced by Ser, while the F6 position can be substituted with Tyr. These results suggest that the Catch domain can recognize and bind to a variety of substrates containing the sequence motif x[G/A/V/L/I/M/P/F/Y/C/S/T]x[G/S]x[F/Y]x[G/A/V/L/I/M/P/F/Y/C/S/T]x or briefly the G/SxF/Y motif (where x represents polar residues) located in an unstructured or loop region on the protein surface, and the hydrophobic interactions and spatial complementarity between the binding motifs of substrates and the Catch domain govern the substrate specificity. Collectively, these findings elucidate the molecular basis for midnolin’s broad substrate specificity.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025081
Resident CD24+LCN2+ liver progenitor cells (LPCs) reportedly contribute to the expanding ductular reaction and macrophage-mediated inflammation associated with chronic liver damage. Both ductular reactions and macrophage-driven inflammation are associated with liver fibrosis and injury in various mouse liver disorders. This study aims to investigate the molecular phenotypes of LPCs and their regulatory mechanisms in humans with non-alcoholic steatohepatitis (NASH). Single-cell RNA sequencing (scRNA-seq) datasets are used to characterize the status and molecular phenotypes of LPCs in clinical NASH samples. To elucidate the regulatory mechanisms of LPCs, CellChat and NicheNet are employed to assess cell-cell communication between LPCs and other cell types. The findings are validated using RNA sequencing datasets associated with NASH progression, NASH mouse models (CDAHFD and HFD), and human NASH liver samples. Results show that resident CD24+LCN2+ LPCs are identified and found to be significantly enriched in NASH patients. Cell communication analyses predict strong interactions between LPCs and proinflammatory macrophage subtypes. Additionally, in NASH, the liver recruits peripheral blood mononuclear cell (PBMC)-derived macrophages and polarizes them into proinflammatory subtypes. The macrophage subtype MP-2 is identified as the primary recipient of LPC-derived signals, exhibiting marked hyperactivation of the NF-κB pathway and a strong association with liver fibrosis. Finally, the MP-2 markers COL10A1 and TPPP3 are characterized and validated. In summary, this study reveals that resident CD24+LCN2+ LPCs are activated in NASH and contribute to fibrosis progression by promoting the activation of the proinflammatory COL10A1+TPPP3+ macrophage subtype.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2026018
Doxorubicin (DOX) remains a cornerstone chemotherapeutic agent for malignancies, yet its clinical utility is severely limited by dose-dependent cardiotoxicity, which can lead to progressive left ventricular dysfunction and heart failure. Pleiotrophin (PTN), a heparin-binding growth factor with diverse physiological functions, regulates glucose and lipid metabolism and promotes oxidative energy pathways. However, whether PTN exerts protective effects against DOX-induced cardiotoxicity (DIC) remains unclear. In this study, we establish cellular and animal models of DIC. DOX administration induces pronounced myocardial injury in both models, characterized by impaired ventricular contractility, increased fibrotic remodeling, and reduced cell viability. Concurrently, PTN protein expression is significantly downregulated in cardiomyocytes under DOX treatment. Overexpression of PTN substantially alleviates these pathological changes. In vitro, PTN reduces mitochondrial oxidative stress and apoptosis while restoring energy production and cell viability. In vivo, PTN improves mitochondrial ultrastructure, decreases cardiomyocyte apoptosis, and enhances cardiac function. Mechanistically, PTN directly binds to SIRT1 and activates AMPK phosphorylation at Thr172, triggering a downstream cascade through the AMPK-PGC1α axis that reprograms mitochondrial energy metabolism and attenuates cardiotoxicity. In conclusion, the PTN-SIRT1 axis protects against DIC by reducing oxidative stress and promoting mitochondrial energy homeostasis via the AMPK/PGC1α pathway, highlighting its potential as a novel therapeutic target for preventing chemotherapy-related cardiac injury.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025242
Drug-induced liver injury (DILI) caused by anti-tuberculosis drugs is a serious clinical problem that can lead to acute liver failure and even death. Current diagnosis relies on lagged indicators such as serum transaminase levels, which rise only 48–72 hours after liver injury. This study is the first to systematically analyze the microRNA expression profile of serum exosomes in patients with anti-tuberculosis drug-induced liver injury (TB-DILI) to discover early diagnostic markers. A total of 12 tuberculosis patients and 6 normal controls were included. Serum exosomes were isolated and characterized, and small RNA sequencing identified 701 miRNAs, with 128 differentially expressed between TB-DILI and TB groups. Notably, miR-122-5p was upregulated and has shown early warning value. Target gene prediction and enrichment analysis revealed involvement in GTPase activity regulation, cell migration, and BMP signaling. These findings suggest that exosomal miRNAs, particularly miR-122-5p, may serve as early diagnostic biomarkers for TB-DILI.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025055
Platelets circulate in an inactive form in the body until they contact with defective areas of endothelial cells or encounter a clotting cascade [1]. Activated platelets release and express bioactive substances and acquire the ability to bind plasma fibrinogen. Abnormal activation of platelets is involved in atherosclerosis and thrombosis [2,3]. When platelets are stimulated and activated, phospholipase A2 is activated at the same time, which then cleaves membrane phospholipids and frees arachidonic acid (AA) [4]. The latter catalyzes thromboxane A2 (TXA2) via thromboxane synthetase [5], which is induced by the cyclooxygenase COX-1 to produce prostaglandins G2 and H2 [6]. TXA2 is highly unstable, with a half-life of only 30 s, and it is rapidly hydrolyzed to relatively stable thromboxane B2 (TXB2), which is then converted in the liver to 11-dehydrothromboxane B2 (11dH-TXB2), which has a longer half-life and is excreted in the urine [7]. Dehydrothromboxane B2 is the final stable metabolite of thromboxane A2, which is derived only from arachidonic acid metabolism and can represent thromboxane A2 level in the body [8]. Specifically, by inhibiting the action of COX-1, the most important enzyme in the process of arachidonic acid metabolism, aspirin inhibits the production of thromboxane A2, that is, the concentration of TXA2 affects the effect of aspirin on platelet aggregation. However, the half-life of TXA2 (including the metabolic intermediate TXB2) is too short to be accurately measured, so the detection of its metabolic end product 11dH-TXB2 can very accurately reflect the sensitivity of the body to aspirin [7]. The concentration of 11dH-TXB2 in the serum correlates well with the concentration of 11dH-TXB2 in the urine, so the determination of 11dH-TXB2 in the urine can more effectively reflect the production of TXA2 in vivo [8]. The 11dH-TXB2 concentration needs to be corrected with the urinary creatinine concentration to rule out the effects of the urine concentration and renal function, so random urine samples can be used for testing [6]. Aspirin can acetylate serine at the key site of cyclooxygenase and thus irreversibly inhibits the activity of COX-1, reduces the synthesis of TXA2, and blocks the production of TXA2 and its induced platelet aggregation. Low-dose aspirin (30–75 mg/day) can effectively inhibit 95% of COX-1 activity [7]. Since the production of TXA2 in serum is largely dependent on platelet COX-1 (a therapeutic target of aspirin), 11dH-TXB2 can be used as a monitor for aspirin-induced platelet inhibition [3]. Creatinine is a metabolic byproduct of muscle metabolism that is primarily excreted via glomerular filtration, and its level is indicative of renal function [9]. The 24-h creatinine clearance can also be used to determine the integrity of the sample or to correct the urine sample concentration with the creatinine ratio [10]. Currently, creatinine detection methods include the Jaffe method, enzymolysis spectrophotometry, HPLC, capillary electrophoresis, capillary zone electrophoresis, gas chromatography tandem mass spectrometry (GC-MS) and liquid chromatography tandem mass spectrometry (LC-MS/MS) [11]. At present, there is no method for the simultaneous detection of 11dH-TXB2 and creatinine. When both analytes are needed, separate tests must be performed, increasing the workload and sample volume requirements. Thus, developing a method that enables the concurrent quantification of 11dH-TXB2 and creatinine in a single assay remains a critical challenge. The aim of this study was to provide a method for the simultaneous detection of 11dH-TXB2 and creatinine and to alleviate the problem that 11dH-TXB2 and creatinine cannot be simultaneously detected. By developing a standardized quantitative approach for measuring 11dHTXB2 and creatinine in human urine, this study aims to provide reliable concentration data, thereby facilitating further clinical research and methodology optimization.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025208
To determine whether lncRNA HNF1A-AS1 affects epithelial ovarian cancer (EOC) growth and macrophage polarization through miR-214/SEMA4D, the endogenous HNF1A-AS1 and miR-214 levels in human EOC cell lines are compared with those in normal ovarian epithelial IOSE80 cells. HNF1A-AS1 is overexpressed or silenced to investigate whether HNF1A-AS1 regulates miR-214/SEMA4D in SKOV3 cells and xenograft tumors, as well as the phenotypic switching of THP-1 cells. Compared with IOSE80 cells, EOC cells present significantly higher HNF1A-AS1 level and lower miR-214 level. Fluorescence in situ hybridization reveals predominant cytoplasmic localization of HNF1A-AS1, supporting its role as a competing endogenous RNA. HNF1A-AS1 and miR-214 antagonize each other in SKOV3 cells. In vitro, HNF1A-AS1 inhibits SKOV3 apoptosis and promotes migration and invasion. HNF1A-AS1 overexpression enhances miR-214 downstream of SEMA4D/PLEXIN-B1/TIAM1/RAC signaling, but miR-214 mimics significantly reverses this effect. Compared with control tumors, xenograft tumors derived from HNF1A-AS1-overexpressing SKOV3 cells present increased tumor growth, attenuated miR-214 expression, and activated SEMA4D/PLEXIN-B1/TIAM/RAC signaling. Knockdown of HNF1A-AS1 has the opposite effects. Additionally, HNF1A-AS1 promotes M2 phenotypic switching in THP-1 cells, which could be reversed by miR-214 overexpression or SEMA4D silencing. Our study suggests that by antagonizing miR-214, HNF1A-AS1 activates the SEMA4D/PLEXIN-B1/TIAM/RAC pathway, facilitating EOC growth and potentially promoting M2 macrophage polarization in the tumor microenvironment. HNF1A-AS1 represents a compelling therapeutic target for treating EOC.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2024221
Ferroptosis is a type of programmed death characterized by iron-dependent lipid peroxidation, and targeting ferroptosis has been shown to efficiently kill highly aggressive cancer cells. Previously, we confirmed that nuclear receptors regulate ferroptosis in pancreatic cancer. However, whether nuclear receptor co-activators regulate ferroptosis is unclear. Here, we show that knocking down the nuclear receptor co-activator, NCOA6, enhances the sensitivity of pancreatic cancer cells to ferroptosis. Mechanistically, NCOA6 knockdown promotes the expression of ACSL4 while inhibiting the expression of SCD1, resulting in changes in lipid metabolism, sensitivity to RSL3-induced ferroptosis, and sensitivity to gemcitabine in pancreatic cancer. The relationships between NCOA6 and ACSL4 or SCD1 are further explored in clinical specimens. This study reveals that targeting NCOA6 might alleviate gemcitabine resistance in pancreatic cancer.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025013
Platinum-based chemotherapy remains the mainstay for non-small cell lung cancer (NSCLC), but it frequently causes dose-limiting myelosuppression, with significant individual variability in susceptibility. However, the genetic basis of myelosuppression side effects remains elusive, greatly hindering personalized therapeutic approaches. In this study, we perform a comprehensive genome-wide association analysis on 491 NSCLC patients receiving platinum-based chemotherapy, examining 4,690,998 single-nucleotide polymorphisms (SNPs) to identify relevant genetic variants. LDBlockShow, FUMA, and MAGMA are utilized to explore linkage disequilibrium, expression quantitative trait loci (eQTLs), chromatin interaction, and conduct gene-based and gene set-based analysis of candidate SNPs. The GWAS results reveal that rs6856089 and its linked SNPs are significantly associated with platinum-based chemotherapy-induced myelosuppression. Specifically, patients with the A allele of rs6856089 have a significantly lower risk of myelosuppression [odds ratio (OR) = 0.1300, P = 7.59 × 10–8]. Furthermore, gene-based analysis reveals that EMCN (P = 2.47 × 10–5), which encodes endomucin, a marker for hematopoietic stem cells, might mediate myelosuppression. This study provides a scientific basis for the individual differences in platinum-based chemotherapy-induced myelosuppression.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2024208
Escherichia coli is widely used in industrial chemical synthesis but faces significant challenges due to bacteriophage contamination, which reduces product quality and yield. Therefore, developing an efficient antiphage system is essential. In this study, we develop a CRISPR-Cas9-based antiphage system (CAPS) targeting essential genes of the T7 phage (gene 5 and gene 19) with single gRNAs transformed into MG1655 strains expressing Cas9. While CAPS provides limited resistance, with plating efficiencies ranging from 10–5 to 10–1, further optimization is needed. To enhance efficacy, we design a double-site-targeting CRISPR-Cas9-based antiphage system (D-CAPS). D-CAPS demonstrates complete resistance, with no plaques observed even at a high multiplicity of infection (MOI of 2), and growth curve analysis reveals that antiphage E. coli strains grow normally, similar to the wild-type strain, even at a high multiplicity of infection. Furthermore, D-CAPS is effective against BL21(DE3) strains, showing strong resistance and demonstrating its versatility across different E. coli strains. Protein expression analysis via green fluorescent protein confirms that E. coli carrying D-CAPS could maintain normal protein expression levels even in the presence of phages, comparable to wild-type strains. Overall, D-CAPS offers a robust and versatile approach to enhancing E. coli resistance to phages, providing a practical solution for protecting industrial E. coli strains and improving fermentation processes.
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.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•2025•DOI: 10.3724/abbs.2024183
Traumatic brain injury (TBI) is a recognized global public health problem. However, there are still limitations in the available therapeutic approaches and a lack of clinically effective drugs. Therefore, an in-depth exploration of the secondary pathological mechanism of TBI and the identification of new effective drugs are urgently needed. Cannabidiol (CBD), a component derived from the cannabis plant, has potential therapeutic effects on neurological diseases and has received increasing attention. However, few reports on CBD intervention in TBI patients exist. Here, we use the Feeney free-fall method to establish a rat TBI model. CBD significantly improves neurological deficit scores, neuronal damage and blood-brain barrier permeability in rats and significantly inhibits the expressions of the brain injury markers S-100β and NSE. Mechanistically, CBD attenuates TBI-induced astrocyte activation, reduces inflammation, and attenuates the expressions of inflammatory prostaglandin system indicators. The use of TG6-10-1 (EP2 inhibitor) and H-89 (PKA inhibitor) indicates that CBD attenuates TBI-induced neurological damage via the PGE2-EP2-cAMP-PKA signaling pathway. Overall, this research provides a novel drug candidate for the treatment of clinical brain trauma.
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•2025•DOI: 10.3724/abbs.2024228
Annexins are a family of multifunctional calcium-dependent and phospholipid-binding proteins that are widely distributed in the plant kingdom. They have a highly conserved evolutionary history that dates back to single-celled protists. Plant annexins, as soluble proteins, can flexibly bind to endomembranes and plasma membranes, exhibiting unique calcium-dependent and calcium-independent characteristics. Members of the annexin family have diverse functions, including binding to F-actin, participating in ATP and GTP hydrolysis, and even serving as peroxidases or cation channels. Annexins play pivotal roles in plant growth and stress signaling. They can respond sensitively to environmental, metabolic, and developmental signals, thereby affecting cytoskeleton remodeling and exocytosis mechanisms. Plant annexin gene families have been successfully identified in multiple species, and their expression and intracellular localization are precisely regulated by developmental processes and environmental factors. Although research on plant annexins has aroused great interest, their depth and breadth still need further expansion compared with those of animal annexins. This article provides a comprehensive and in-depth review of the characteristics and functions of plant annexin families, revealing their core roles in plant growth and adaptation, and yielding valuable references and insights for future research.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025112
Ferroptosis is a lytic form of regulated cell death that is driven by iron-dependent lipid peroxidation and has been implicated in various diseases, including acute kidney injury (AKI). Scutellarin is a flavonoid isolated from Erigeron breviscapus (Vant.) Hand.-Mazz. and possesses various pharmacological activities, including anti-inflammatory and antioxidative properties. However, it is unclear whether scutellarin can inhibit ferroptosis and mitigate related diseases. In this study, we show that scutellarin can inhibit ferroptosis in both human HK-2 cells and mouse bone marrow-derived macrophages stimulated with RSL3 or erastin. Mitochondrial dysfunction and reactive oxygen species generation are counteracted by scutellarin treatment, suggesting the involvement of its antioxidative activity. Furthermore, scutellarin increases the nuclear levels of Nrf2 and the expressions of its target genes, including HO-1 and GPX4. Scutellarin-mediated inhibition of ferroptosis and increases in these proteins are abrogated by co-treatment with brusatol, an Nrf2 inhibitor, indicating an essential role for Nrf2 in this process. In a mouse model of folic acid-induced AKI, scutellarin mitigates acute renal damage, as revealed by histopathological analysis and serum blood urea nitrogen and creatinine assays. Folic acid-induced acute renal injury is associated with increased ferroptosis, as revealed by elevated level of 4-hydroxynonenal (4-HNE), a surrogate marker of ferroptosis, which is diminished by scutellarin co-treatment. Specifically, the elevated 4-HNE levels in macrophages (MAC-2 positive) and other renal cells are suppressed by scutellarin. Overall, scutellarin can inhibit ferroptosis both in cultured cells and in a mouse model of AKI by regulating Nrf2 signaling.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025135
Despite the high efficacy of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) in treating acute promyelocytic leukemia (APL), approximately 10%–20% of patients develop drug resistance due to mutations in PML-RARα and other factors. Here, we find that inhibition of USP2 with ML364 or USP2 silencing reduces PML-RARα protein levels in both ATRA-sensitive and ATRA-resistant APL cells, and this effect is reversed by proteasome inhibition. Conversely, USP2 overexpression enhances PML-RARα stability. Mechanistically, USP2 interacts with and deubiquitinates PML-RARα, including its drug-resistant mutants. Consistent with PML-RARα degradation, ML364 treatment significantly induces apoptosis in APL cell lines and primary leukemia cells. In conclusion, this study identifies USP2 as a novel deubiquitinating enzyme for PML-RARα and highlights USP2 inhibition as a potential therapeutic strategy for APL with PML-RARα mutations.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025197
Acute myeloid leukemia (AML) is a clinically aggressive hematologic malignancy characterized by high relapse rates and treatment resistance, highlighting the need for novel biomarkers to improve clinical outcomes. In this study, we explore the roles of nuclear receptor-interacting protein 1 (NRIP1) in AML, focusing on its associations with tumor progression and immune infiltration. Analysis of public AML gene expression datasets reveals that NRIP1 expression is significantly increased in AML patients. Those with high NRIP1 expression have markedly shorter overall survival than those with low expression. Furthermore, NRIP1 expression is significantly associated with the infiltration of diverse immune cells, including B cells, dendritic cells, T cells, mast cells, eosinophils, and T helper cells, suggesting that NRIP1 may be a regulator of immune cell infiltration. Functional enrichment analysis indicates that NRIP1 and its interacting partners are involved in tumorigenesis, immune microenvironment remodeling, and metabolic reprogramming. Survival analysis confirms the prognostic value of NRIP1. Importantly, functional validation in AML cell lines confirms that NRIP1 knockdown suppresses proliferation and induces apoptosis. Our study identifies NRIP1 as a multifaceted regulator that promotes AML by driving tumor progression, regulating immune cell infiltration, and modulating ferroptosis, highlighting its role as a novel prognostic biomarker.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025075
Chondrocytes store lipids in the form of lipid droplets (LDs) and maintain cartilage lipid metabolic homeostasis by consuming or regenerating LDs. This modulation is largely mediated by a series of biochemical factors. Fibroblast growth factor 8 (FGF8) is one of the most important factors involved in the proliferation, differentiation, and migration of chondrocytes and has attracted increasing attention in the physiology and pathology of cartilage. However, the effect of FGF8 on LD accumulation in chondrocytes remains unclear. This study aims to elucidate the role of FGF8 in LDs and explore the underlying biomechanism involved. The results reveal that FGF8 promotes LD accumulation in chondrocytes by upregulating perilipin1 (Plin1) expression. FGF8 activates the cytoplasmic p-p38 signaling pathway via fibroblast growth factor receptor 1 (FGFR1) to increase LD accumulation in chondrocytes. Subsequent experiments with siRNAs and specific inhibitors further confirm the importance of the FGFR1/p38 axis for LD accumulation in chondrocytes exposed to FGF8. The results increase our understanding of the role of FGF8 in the lipid metabolic homeostasis of chondrocytes and provide insights into the physiology and pathology of cartilage.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2026049
Esophageal squamous cell carcinoma (ESCC) represents a common malignancy of the digestive system. Circular RNAs (circRNAs) are a distinct class of single-stranded non-coding RNAs that are essential in the progression of various tumors given that they can act as microRNA (miRNA) sponges in a manner similar to that of mRNAs. In this study, circ_0006156 is screened to be highly expressed in ESCC tissues through high-throughput sequencing and quantitative real-time polymerase chain reaction. Subsequent in vitro and in vivo experiments are conducted to validate its biological functions. Furthermore, the regulatory relationships among circ_0006156, miR-202-5p, and TGFBR1 are investigated using RNA antisense purification, miRNA sequencing, RNA immunoprecipitation, fluorescence in situ hybridization, dual-luciferase reporter assay, and bioinformatics analyses. The results show significant overexpression of circ_0006156 in ESCC tissues, with relatively shorter overall survival observed in patients with high circ_0006156 expression. circ_0006156 is further identified to directly bind to miR-202-5p. miR-202-5p inhibits the proliferation, migration, and invasion of ESCC cells in vitro and partially rescues the effects induced by circ_0006156. Consistent results are reported by subcutaneous xenograft tumor experiments in nude mice. In addition, circ_0006156 is confirmed to act as an endogenous sponge for miR-202-5p, which results in a relieved suppression of its target gene TGFβR1. In summary, circ_0006156 can regulate TGFβR1 expression by sponging miR-202-5p, which may further activate the TGFβ/Smad pathway and promote ESCC progression. Collectively, circ_0006156 functions as a novel oncogenic RNA in ESCC and may serve as a potential tumor marker.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025235
Over the past decade, immunotherapy has emerged as a pivotal therapeutic strategy in cancer treatment. Immune checkpoint inhibitors (ICIs), such as CTLA-4 and PD-1 monoclonal antibodies, have demonstrated remarkable clinical efficacy in different types of cancer. However, the overall success rate of immune checkpoint therapies remains low. Investigating alternative immune checkpoint molecules is imperative. T-cell immunoglobulin and mucin-containing molecule-3 (TIM-3), which is expressed in T cells, natural killer (NK) cells, macrophages, and dendritic cells, has gained recognition as a promising candidate for tumor immunotherapy. Targeting TIM-3 represents a promising approach for cancer immunotherapy, particularly through the rational design of novel combination therapies with other ICIs. In this review, we present a comprehensive summary of the research advancements concerning the role of TIM-3 in regulating immune responses in different cell types and explore theoretical frameworks for targeting TIM-3 to achieve more effective immunotherapeutic breakthroughs.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025192
Gut inflammatory diseases, including inflammatory bowel disease (IBD), infectious enteritis, and other inflammatory conditions, are among the most common non-neoplastic intestinal disorders. Their pathogenesis is often driven by an imbalance between pro-inflammatory and anti-inflammatory signals, with immune cells playing pivotal roles in maintaining this equilibrium. Immune cells in the gut exhibit complex, multifaceted functions: they eliminate pathogens, promote tissue repair, and counteract tumors, but excessive immune activation can exacerbate tissue damage and disease progression. Notably, metabolic reprogramming in inflammatory contexts serves as a key regulator of immune cell function and phenotypic switching. This includes alterations in cellular energy metabolism (e.g., macrophage polarization via disrupted glycolysis or fatty acid oxidation) and the modulation of immune responses by microenvironmental metabolites (e.g., bile acid-mediated Th17/Treg balance). While alterations in immune cell function and composition within the inflammatory milieu are well-established, the significance of disease-associated metabolic reprogramming—specifically how metabolism regulates immune cell function—has garnered increasing attention. This review explores how cellular metabolic reprogramming, changes in the metabolic microenvironment, and gut dysbiosis collectively influence the differentiation, proliferation, and function of immune cells in various intestinal inflammatory diseases, as well as their impact on disease progression.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2026081
Multiple myeloma (MM) patients frequently experience relapse, disease progression, and drug resistance, necessitating novel therapeutic strategies. This study investigates the role of peptidylprolyl isomerase A (PPIA) in mediating dihydroartemisinin (DHA)-induced ferroptosis in MM. Building on our previous work establishing the prognostic relevance of ferroptosis in MM, we elucidate the mechanism by which DHA triggers this form of cell death through the disruption of iron metabolism and redox homeostasis. DHA significantly reduces the viability of MM cell lines and primary CD138+ cells derived from patient bone marrow samples and attenuates tumor burden in orthotopic MM models. Mechanistically, DHA upregulates the iron-regulatory genes transferrin receptor 1 (TFRC) and heme oxygenase-1 (HMOX1), thereby perturbing iron homeostasis and promoting ferroptosis. Crucially, DHA targets the oxidized form of PPIA, a redox-sensitive chaperone, binding to it and preventing its reduction, which elevates intracellular reactive oxygen species (ROS). Combined treatment with DHA and erastin, which concurrently disrupt iron and amino acid metabolism, exerts synergistic cytotoxicity and enhances MM inhibition. Furthermore, in a syngeneic mouse model, DHA promotes T-cell activation and augments tumor suppression. Collectively, these findings underscore PPIA’s pivotal role in a novel ferroptotic cell death pathway and reveal new therapeutic opportunities for MM.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024102
Synovial inflammation plays a key role in osteoarthritis (OA) pathogenesis. Fibroblast-like synoviocytes (FLSs) represent a distinct cell subpopulation within the synovium, and their unique phenotypic alterations are considered significant contributors to inflammation and fibrotic responses. The underlying mechanism by which acetyl-11-keto-β-boswellic acid (AKBA) modulates FLS activation remains unclear. This study aims to assess the beneficial effects of AKBA through both in vitro and in vivo investigations. Network pharmacology evaluation is used to identify potential targets of AKBA in OA. We evaluate the effects of AKBA on FLSs activation in vitro and the regulatory role of AKBA on the Nrf2/HO-1 signaling pathway. ML385 (an Nrf2 inhibitor) is used to verify the binding of AKBA to its target in FLSs. We validate the in vivo efficacy of AKBA in alleviating OA using anterior cruciate ligament transection and destabilization of the medial meniscus (ACLT+DMM) in a rat model. Network pharmacological analysis reveals the potential effect of AKBA on OA. AKBA effectively attenuates lipopolysaccharide (LPS)-induced abnormal migration and invasion and the production of inflammatory mediators, matrix metalloproteinases (MMPs), and reactive oxygen species (ROS) in FLSs, contributing to the restoration of the synovial microenvironment. After treatment with ML385, the effect of AKBA on FLSs is reversed. In vivo studies demonstrate that AKBA mitigates synovial inflammation and fibrotic responses induced by ACLT+DMM in rats via activation of the Nrf2/HO-1 axis. AKBA exhibits theoretical potential for alleviating OA progression through the Nrf2/HO-1 pathway and represents a viable therapeutic candidate for this patient population.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024078
Neural tube defects (NTDs) are characterized by the failure of neural tube closure during embryogenesis and are considered the most common and severe central nervous system anomalies during early development. Recent microRNA (miRNA) expression profiling studies have revealed that the dysregulation of several miRNAs plays an important role in retinoic acid (RA)-induced NTDs. However, the molecular functions of these miRNAs in NTDs remain largely unidentified. Here, we show that miR-10a-5p is significantly upregulated in RA-induced NTDs and results in reduced cell growth due to cell cycle arrest and dysregulation of cell differentiation. Moreover, the cell adhesion molecule L1-like (Chl1) is identified as a direct target of miR-10a-5p in neural stem cells (NSCs) in vitro, and its expression is reduced in RA-induced NTDs. siRNA-mediated knockdown of intracellular Chl1 affects cell proliferation and differentiation similar to those of miR-10a-5p overexpression, which further leads to the inhibition of the expressions of downstream ERK1/2 MAPK signaling pathway proteins. These cellular responses are abrogated by either increased expression of the direct target of miR-10a-5p (Chl1) or an ERK agonist such as honokiol. Overall, our study demonstrates that miR-10a-5p plays a major role in the process of NSC growth and differentiation by directly targeting Chl1, which in turn induces the downregulation of the ERK1/2 cascade, suggesting that miR-10a-5p and Chl1 are critical for NTD formation in the development of embryos.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024114
With the increasing global population and aging demographic, the incidence of stroke is rising. Among these, ischemic stroke (IS), also known as cerebral ischemia, constitutes over 80% of all stroke cases. This condition is characterized by an acute cerebrovascular disease caused by the blockage and interruption of the brain's blood supply, resulting in localized tissue ischemia, oxygen, and glucose deficiency, ultimately leading to the death of nerve cells and tissue necrosis [1,2]. "Vascular recanalization and the restoration of cerebral blood flow" are the primary clinical treatment objectives and are achieved through the intravenous administration of drugs such as tissue plasminogen activator or through surgical thrombectomy. These interventions not only restore the delivery of oxygen and glucose to the affected cerebral area but also help prevent the expansion of the infarcted region. However, the restoration of reperfusion cerebral blood flow similarly exposes the infarct area to peripheral immune cells, triggering the activation of the immune response and inflammation-induced injury [3]. Research indicates that IS elicits a robust inflammatory response, with neuroinflammation playing a crucial role in the secondary neurodegeneration process following stroke. Neuroinflammatory responses are initiated and perpetuated through injury cascades that include the release of inflammatory mediators, the migration and recruitment of white blood cells across the blood-brain barrier, and the impairment of endothelial nitric oxide synthase. These mechanisms collectively promote the activation of pro-inflammatory genes, which in turn activate microglia (MG) and exacerbate ischemic damage and neurological dysfunction [4]. MG are resident immune cells of the central nervous system (CNS). Its function is akin to that of macrophages, serving as the first line of defense against injuries within the central nervous system. Under typical conditions, brain microglia participate in immune surveillance and defense against infectious agents. However, in the pathogenesis of neurodegenerative diseases such as IS, MG are activated by various stimuli. Once activated, MG are known to release numerous proinflammatory or cytotoxic factors, such as inducible nitric oxide synthase (iNOS), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and reactive oxygen species (ROS). These factors initiate the neuroinflammatory response, exacerbate inflammation, intensify damage to brain tissue and neurons, and significantly hinder the repair of brain injuries and neurogenesis [5,6]. Therefore, inhibiting the activation of microglia and reducing the inflammatory response in the central nervous system are crucial for minimizing brain damage caused by IS and are vital for developing effective prevention and treatment strategies. In recent years, certain natural compounds extracted from traditional drug formulations have shown high therapeutic potential in protecting the brain from cerebral ischemic injury. These compounds reduce the neuroinflammatory response and apoptosis following stroke. Traditional Chinese herbal medicine (TCHM) and its constituent herbs feature a multiplicity of components, targets, and pathways owing to their complex formulations and therapeutic principles, making them promising sources for developing effective treatments for IS. Panax notoginseng saponin (PNS), as the principal bioactive component of Panax notoginseng, is extensively utilized in the prevention and treatment of cardiovascular and cerebrovascular diseases. Its pharmacological benefits include dissipating blood stasis, promoting hemostasis, alleviating swelling and pain, regulating energy metabolism disorders, balancing ion metabolism, and reducing and accelerating the clearance of free radicals [7]. Research indicates that PNS mitigates apoptosis by maintaining mitochondrial homeostasis, enhancing the integrity of the blood‒brain barrier (BBB), augmenting cerebral blood supply, and fostering the differentiation of neural stem cells and proliferation of hippocampal neurons. In addition, PNS offers neuroprotection against focal cerebral I/R injury in rats by reducing brain edema, upregulating the expression of the heat shock protein HSP70, and downregulating the expression of transferrin [8,9]. Additionally, PNS has been reported to enhance the recovery of neurogenesis and neurological function in cerebral embolism induced by microspheres and to reduce sepsis-induced acute kidney injury by suppressing inflammation [10]. However, the mechanism by which PNS targets IS has not been fully elucidated. In this study, we investigated the anti-inflammatory effects of PNS on IS and identified potential target pathways that could inhibit microglia-mediated inflammatory response.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024024
Myocardial ischemia/reperfusion (I/R) injury is a classic type of cardiovascular disease characterized by injury to cardiomyocytes leading to different types of cell death. The degree of irreversible myocardial damage is closely related to age, and ferroptosis is involved in cardiomyocyte damage. However, the mechanisms underlying ferroptosis regulation in aging myocardial I/R injury are still unclear. The present study aims to explore the underlying mechanism of piRNA regulation in ferroptosis. Using left anterior descending coronary artery ligation in an aging rat model and a D-galactose-induced rat cardiomyocyte line (H9C2) to construct an aging cardiomyocyte model, we investigate whether ferroptosis occurs after reperfusion injury in vitro and in vivo. This study focuses on the upregulation of piR-000699 after hypoxia/reoxygenation treatment in aging cardiomyocytes by observing hypoxia/reoxygenation (H/R) injury indicators and ferroptosis-related indicators and clarifying the role of piR-000699 in H/R injury caused by ferroptosis in aging cardiomyocytes. Bioinformatics analysis reveals that SLC39A14 is a gene that binds to piR-000699. Our data show that ferroptosis plays an important role in I/R injury both in vivo and in vitro. Furthermore, the results show the potential role of piR-000699 in regulating SLC39A14 in ferroptosis in aging cardiomyocytes under hypoxia/reoxygenation conditions. Together, our results reveal that the mechanism by which piR-000699 binds to SLC39A14 regulates ferroptosis in aging myocardial I/R injury.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024127
Protein O-glycosylation, also known as mucin-type O-glycosylation, is one of the most abundant glycosylation in mammalian cells. It is initially catalyzed by a family of polypeptide GalNAc transferases (ppGalNAc-Ts). The trimeric spike protein (S) of SARS-CoV-2 is highly glycosylated and facilitates the virus’s entry into host cells and membrane fusion of the virus. However, the functions and relationship between host ppGalNAc-Ts and O-glycosylation on the S protein remain unclear. Herein, we identify 15 O-glycosites and 10 distinct O-glycan structures on the S protein using an HCD-product-dependent triggered ETD mass spectrometric analysis. We observe that the isoenzyme T6 of ppGalNAc-Ts (ppGalNAc-T6) exhibits high O-glycosylation activity for the S protein, as demonstrated by an on-chip catalytic assay. Overexpression of ppGalNAc-T6 in HEK293 cells significantly enhances the O-glycosylation level of the S protein, not only by adding new O-glycosites but also by increasing O-glycan heterogeneity. Molecular dynamics simulations reveal that O-glycosylation on the protomer-interface regions, modified by ppGalNAc-T6, potentially stabilizes the trimeric S protein structure by establishing hydrogen bonds and non-polar interactions between adjacent protomers. Furthermore, mutation frequency analysis indicates that most O-glycosites of the S protein are conserved during the evolution of SARS-CoV-2 variants. Taken together, our finding demonstrate that host O-glycosyltransferases dynamically regulate the O-glycosylation of the S protein, which may influence the trimeric structural stability of the protein. This work provides structural insights into the functional role of specific host O-glycosyltransferases in regulating the O-glycosylation of viral envelope proteins.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025213
Myocardial infarction (MI) causes irreversible cardiomyocyte loss, creating a need for cardiac repair therapies. The role of cell division cycle 5-like (CDC5L), a cell cycle regulator, in cardiac repair is unknown. This study aims to define the role of CDC5L in mitigating ischemia-reperfusion (I/R) injury by assessing its impact on cardiomyocyte proliferation and apoptosis and to determine the mechanism involving the FGF10-YAP axis. We model cardiac injury using in vitro oxygen-glucose deprivation/reoxygenation (OGD/R) in neonatal mouse cardiomyocytes and in vivo I/R in adult mice. To investigate CDC5L function, we modulate its expression via adenoviral or AAV9-mediated overexpression or knockdown. Proliferation markers (EdU+, Ki67+, pH3+), apoptosis (TUNEL staining, Bax/Bcl-2 ratio), and cardiac function (echocardiography) are assessed. Through transcriptomic screening, we identify CDC5L downstream targets and validate their functional roles using FGF10 knockdown rescue assays. We find that CDC5L is upregulated in the post-I/R murine myocardium. Its overexpression enhances cardiomyocyte proliferation, preserves cardiac function, reduces apoptosis, and diminishes infarct size. Transcriptomic analysis identifies FGF10 as a key downstream effector, and we confirm that CDC5L upregulates FGF10 expression. Notably, FGF10 knockdown reverses the proliferative and anti-apoptotic effects of CDC5L. Moreover, the CDC5L-mediated reduction in YAP phosphorylation is also dependent on FGF10, as this effect is abolished upon FGF10 knockdown. In conclusion, CDC5L attenuates cardiac I/R injury by promoting cardiomyocyte proliferation and inhibiting apoptosis through the FGF10-YAP pathway. This CDC5L-FGF10-YAP axis represents a promising therapeutic target to improve myocardial regeneration and recovery after myocardial infarction.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025092
Accumulating evidence suggests that NLRP3-mediated alveolar macrophage (AM) pyroptosis and subsequent high mobility group box protein 1 (HMGB1) secretion play significant roles in the pathogenesis of acute respiratory distress syndrome (ARDS). Nrf2 has been shown to be individually involved in regulating pyroptosis. In this study, we investigate the ability of CDDO-imidazolide, a potent Nrf2 activator, to regulate AM pyroptosis and HMGB1 secretion in sepsis-associated ARDS, along with its underlying mechanism. The in vitro alveolar macrophage (AM) pyroptosis model, established by stimulating J774A.1 cells with LPS and ATP, was treated with CDDO-imidazolide or utilized Nrf2-knockout cells. The mice are intraperitoneally administered with CDDO-imidazolide before the in vivo sepsis-associated ARDS model is constructed via caecal ligation perforation and the Nrf2 inhibitor, ML385. In vitro studies reveal that the use of 3-MA to prohibit PINK1/Parkin-dependent mitophagy aggravates NLRP3-mediated pyroptosis and HMGB1 release in J774A.1 cells via LPS and ATP exposure. CDDO-imidazolide also significantly prevents NLRP3-mediated pyroptosis and HMGB1 release to increase PINK1/Parkin-dependent mitophagy, but these effects are not detected in Nrf2-knockout macrophages. Most importantly, CDDO-imidazolide significantly alleviates NLRP3 inflammasome protein expression in the lung tissues of septic mice and HMGB1 protein levels in the serum and bronchoalveolar lavage fluid (BALF), which can be reversed by ML385. Taken together, our results demonstrate that CDDO-imidazolide prominently protects the lungs by promoting Nrf2 activation and enhancing PINK1/Parkin mitophagy to inhibit AM pyroptosis and HMGB1 release. These findings provide novel insights for therapeutic strategies for sepsis-associated ARDS.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025080
Macrophages are key players in the pathology of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Existing studies and our previous studies have documented the role of CD206-positive M2 macrophages in the inflammatory process of AAV. Inflammasome activation is a critical pathway through which macrophages release inflammatory factors. In this study, we investigate the role of the inflammasome in macrophages in AAV and explore the role of CD206 in this process. We recruit newly diagnosed AAV patients and disease controls from our department. The expression and localization of the NOD-like receptor family, pyrin domain containing 3 (NLRP3) and CD206 in the kidney are determined via immunofluorescence experiments. Myeloperoxidase (MPO)-ANCA immunoglobulin G (MPO-ANCA IgG) is purified from new-onset AAV patients with MPO-ANCA and used to treat lipopolysaccharide (LPS)-primed macrophages in vitro. Our findings reveal that NLRP3 expression is significantly elevated in the kidneys of active AAV patients, accompanied by increased cleaved caspase-1 and N-terminal gasdermin-D (GSDMD) levels in peripheral blood mononuclear cells (PBMCs). In vitro, MPO-ANCA IgG induces NLRP3 inflammasome activation and interleukin (IL)-1β production in macrophages, which is associated with increased MPO expression and JNK signaling pathway activation. Immunofluorescence analysis demonstrates partial colocalization of CD206 and NLRP3 in AAV kidneys. Furthermore, silencing of MRC1 gene, which encodes CD206, reduces inflammasome activation induced by MPO-ANCA IgG. In conclusion, our study provides evidence that MPO-ANCA IgG contributes to NLRP3 inflammasome activation and macrophage pyroptosis, with CD206 playing a critical role in this process. These findings elucidate the mechanisms underlying inflammation in AAV and suggest potential therapeutic targets.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2024226
Glutaminolysis and glycolysis promote the malignant progression of colorectal cancer. The role of activating transcription factor 4 (ATF4) in solute carrier family 1 member 5 (SLC1A5)-mediated glutaminolysis and glycolysis remains to be elucidated. SLC1A5 and ATF4 expression levels are detected in colorectal cancer tissues. ATF4 is knocked down or overexpressed to assess its role in cell viability, migration and invasion. SLC1A5 is knocked down to evaluate its role in cell viability, migration, invasion, and metastasis and the metabolism of glutamine and glucose. The regulatory effect of the transcription factor ATF4 on SLC1A5 transcription and expression is determined using a luciferase reporter assay and chromatin immunoprecipitation (ChIP) techniques. Upregulated ATF4 and SLC1A5 expressions are observed in tumor tissue, which is positively correlated with the tumor, node, and metastasis (TNM) stages. ATF4-overexpressing SW480 cells show the increased cell viability, migration and invasion. Conversely, ATF4 knockdown decreases the viability, migration and invasion of HCT-116 cells. SLC1A5 knockdown inhibits viability, migration, invasion, and metastasis and the metabolism of glutamine and glucose in HT-29 cells, as well as the expressions of two key glycolytic enzymes, hexokinase 2 (HK2) and pyruvate kinase M2 (PKM2). The luciferase activity of the SLC1A5 promoter is increased by ATF4 overexpression. SLC1A5 promoter enrichment is increased by anti-ATF4 antibody immunoprecipitation in ATF4-overexpressing colorectal cells, indicating that ATF4 targets SLC1A5 to promote glutamine and glucose metabolism in these cells. In summary, the ATF4/SLC1A5 axis plays a significant role in the progression of colorectal cancer by regulating glutamine metabolism and glycolysis.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024086
Endothelial dysfunction (ED) serves as the pathological basis for various cardiovascular diseases. Guanosine triphosphate cyclopyrrolone 1 (GCH1) emerges as a pivotal protein in sustaining nitric oxide (NO) production within endothelial cells, yet it undergoes degradation under oxidative stress, contributing to endothelial cell dysfunction. Citronellal (CT), a monoterpenoid, has been shown to ameliorate endothelial dysfunction induced by in atherosclerosis rats. However, whether CT can inhibit the degradation of GCH1 protein is not clear. It has been reported that ubiquitination may play a crucial role in regulating GCH1 protein levels and activities. However, the specific E3 ligase for GCH1 and the molecular mechanism of GCH1 ubiquitination remain unclear. Using data-base exploration analysis, we find that the levels of the E3 ligase Smad-ubiquitination regulatory factor 2 (Smurf2) negatively correlate with those of GCH1 in vascular tissues and HUVECs. We observe that Smurf2 interacts with GCH1 and promotes its degradation via the proteasome pathway. Interestingly, ectopic Smurf2 expression not only decreases GCH1 levels but also reduces cell proliferation and reactive oxygen species (ROS) levels, mostly because of increased GCH1 accumulation. Furthermore, we identify BH4/eNOS as downstream of GCH1. Taken together, our results indicate that CT can obviously improve vascular endothelial injury in Type 1 diabetes mellitus (T1DM) rats and reverse the expressions of GCH1 and Smurf2 proteins in aorta of T1DM rats. Smurf2 promotes ubiquitination and degradation of GCH1 through proteasome pathway in HUVECs. We conclude that the Smurf2-GCH1 interaction might represent a potential target for improving endothelial injury.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025069
Inflammation, while essential for host defense, can contribute to diseases like inflammatory bowel disease (IBD) when dysregulated. IBD involves chronic intestinal inflammation linked to bacterial infection and disruption of the intestinal epithelial barrier (IEB). The IEB maintains intestinal homeostasis, preventing the entry of harmful substances like lipopolysaccharide (LPS) while allowing nutrient absorption. Preserving IEB function is crucial in managing various diseases. Current IBD treatments often have adverse effects, including facial swelling and acne from corticosteroids, and allergic reactions, nausea, elevated liver tests, and pancreatitis from immunomodulators, increasing interest in natural products. Flavonoids, a diverse class of plant metabolites, have shown promising anti-inflammatory properties. Lutonarin (LU), a flavonoid abundant in barley seedlings, has exhibited various biological activities, including anti-inflammatory effects in LPS-stimulated macrophages. However, its specific impacts on IEB function remain unclear. This study aims to investigate the protective effects of LU against LPS-induced IEB dysfunction using an in vitro Caco-2 cell monolayer model. To assess the possible cytotoxicity of LU and optimize the suitable concentration, the viability of Caco-2 cells was assessed by CCK-8 assay. LU concentrations up to 96 μM did not significantly affect cell viability after 24 and 48 h of exposure. To evaluate the protective effect of LU against LPS-induced cytotoxicity, Caco-2 cells were pretreated with LU (3‒96 μM) for 48 h prior to exposure to 15 μg/mL LPS for 24 h. LPS significantly reduced cell viability, while LU pretreatment attenuated this reduction in a concentration-dependent manner. Concentrations of 12 μM LU were selected for subsequent experiments to minimize potential off-target effects. The Caco-2 cell monolayer model, a well-established in vitro system for investigating IEB function, was employed to study the effects of LU on IEB integrity. Barrier integrity was evaluated using transepithelial electrical resistance (TEER) measurements. LPS treatment significantly reduced TEER, indicating impaired barrier function. Pretreatment with 12 μM LU preserved TEER values, suggesting a protective effect against LPS-induced barrier disruption. Furthermore, paracellular permeability was evaluated using fluorescein isothiocyanate-dextran 4 (FITC-dextran, 4 kDa). LPS significantly increased FITC-dextran (FD4) flux, indicating increased permeability. LU pretreatment markedly attenuated this effect, confirming its ability to prevent LPS-induced permeability changes. To detect if LPS and LU pretreatment changes the expressions of tight junction (TJ) proteins Zonula occludens-1 (ZO-1) and Occludin, real-time qPCR and immunofluorescence staining assays were applied. LPS treatment significantly reduced mRNA expression levels of TJ proteins ZO-1 and Occludin. LU pretreatment effectively mitigated this downregulation, restoring their expression to levels comparable to the CON group.
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•2024•DOI: 10.3724/abbs.2024068
Transient receptor potential channel subfamily vanilloid 1 (TRPV1) is a member of the transient receptor potential family of nonselective cationic transmembrane channel proteins that are involved in the regulation of calcium homeostasis. It is expressed in various tumor types and has been implicated in the regulation of cancer growth, metastasis, apoptosis, and cancer-related pain. TRPV1 is highly expressed in triple-negative breast cancer (TNBC), and both its agonists and antagonists may exert anti-cancer effects. In this review, we provide an overview of the effect of TRPV1 on TNBC development and its influence on immunotherapy in an attempt to facilitate the development of future treatment strategies.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2024204
SMARCB1 encodes a core subunit of the SWI/SNF chromatin remodeling complex, which plays a crucial role in the regulation of gene expression. Germline mutations in the SMARCB1 gene have been linked to early childhood Coffin-Siris syndrome type 3 (CSS3), a rare congenital malformation syndrome characterized by severe developmental delay and intellectual disability. In this study, we report a family of two adult CSS3 patients with a novel missense SMARCB1 mutation (c.1091A>C, p.Lys364Thr) identified through whole-exome sequencing (WES). Both patients exhibit selective difficulties in verbal learning and experience language delays. Additionally, the development of meningioma is confirmed in one of the patients. Mechanistic studies suggest that this missense mutation may abnormally activate the MAPK signaling pathway, which is implicated in the pathogenesis of tumor progression and neurodevelopmental disorders. This is the first reported case of a germline mutation in the SMARCB1 gene associated with both CSS3 and meningioma, thereby expanding the phenotypic spectrum of SMARCB1-related disorders.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2024186
Pyruvate dehydrogenase kinase 1 (PDK1) is a new therapeutic target that is dysregulated in multiple tumors. This study aims to explore the potential role and regulatory mechanism of PDK1 in epithelial ovarian cancer (EOC). We detect PDK1 expression in EOC tissues and cells using qRT-PCR and western blot analysis, and the effects of PDK1 on EOC cell malignant behaviors are explored. RNA sequencing analyses are performed to explore the differentially expressed genes in PDK1-silenced EOC cells. Furthermore, tumor-bearing mouse models are established to assess the impacts of PDK1 and BGN on EOC tumor growth and metastasis in vivo. The results show that PDK1 is upregulated in EOC tissues and cell lines. Biglycan (BGN) is downregulated in PDK1-silenced EOC cells, and its expression is positively correlated with PDK1 levels in EOC tissues. PDK1 depletion inhibits EOC cell proliferation, migration and invasion. Mechanistically, PDK1 and BGN are colocalized in the cytoplasm of EOC cells and interact with each other. PDK1 positively regulates BGN expression by enhancing BGN mRNA stability. BGN overexpression partially reverses the anti-tumor effects of PDK1 depletion on EOC cell malignant behaviors. PDK1 has also been revealed to upregulate BGN to activate the NF-κB oncogenic pathway in EOC cells. Additionally, PDK1 accelerates tumor growth and metastasis by modulating BGN expression. In conclusion, PDK1 functions as an oncogene, facilitating EOC progression by upregulating BGN and activating the NF-κB pathway. These findings may provide valuable biomarkers for the diagnosis and treatment of EOC.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024056
Biological control of pests and pathogens has attracted much attention due to its green, safe and effective characteristics. However, it faces the dilemma of insignificant effects in large-scale applications. Therefore, an in-depth exploration of the metabolic potential of biocontrol fungi based on big omics data is crucial for a comprehensive and systematic understanding of the specific modes of action operated by various biocontrol fungi. This article analyzes the preferences for extracellular carbon and nitrogen source degradation, secondary metabolites (nonribosomal peptides, polyketide synthases) and their product characteristics and the conversion relationship between extracellular primary metabolism and intracellular secondary metabolism for eight different filamentous fungi with characteristics appropriate for the biological control of bacterial pathogens and phytopathogenic nematodes. Further clarification is provided that Paecilomyces lilacinus, encoding a large number of hydrolase enzymes capable of degrading pathogen protection barrier, can be directly applied in the field as a predatory biocontrol fungus, whereas Trichoderma, as an antibiosis-active biocontrol control fungus, can form dominant strains on preferred substrates and produce a large number of secondary metabolites to achieve antibacterial effects. By clarifying the levels of biological control achievable by different biocontrol fungi, we provide a theoretical foundation for their application to cropping habitats.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2024210
Esophageal squamous cell carcinoma (ESCC) is one of the most common forms of malignancy worldwide. However, there is currently a lack of effective chemotherapeutic drugs for ESCC. Ivermectin is a broad-spectrum antiparasitic drug with notable antitumor activity. However, the cellular and molecular mechanisms by which ivermectin inhibits cancer growth remain unclear. In this study, we elucidate the role of ivermectin in ESCC suppression by activating the endoplasmic reticulum (ER) stress and autophagy pathways. In transcriptome analyses, we find that activating transcription factor 4 (ATF4) and DNA damage inducible transcript 3 (DDIT3) are involved in the activation of ER stress by ivermectin. Moreover, ivermectin treatment suppresses the growth of ESCC xenograft tumors in nude mice. Taken together, our results establish the antitumor molecular role of ivermectin in targeting the ER stress-autophagy pathway and suggest that ivermectin is a potential drug candidate for the treatment of ESCC.
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•2025•DOI: 10.3724/abbs.2025015
Graphene and its derivatives exhibit excellent electrical and mechanical properties, including a high specific surface area, excellent electron mobility, and good biocompatibility, which make them ideal materials for fabricating biosensor devices. Nevertheless, sensors based on pure graphene sensors still have certain limitations. For example, the number of dangling chemical bonds on the graphene surface is insufficient, which restricts the chemisorption of target molecules on the graphene surface. Additionally, graphene tends to stack and self-polymerize due to the presence of strong π-π interactions, van der Waals forces, and high surface energy, which leads to limitations in its semiconductor applications. The incorporation of other nanomaterials (e.g., metals, metal oxides, and conductive polymers) into graphene sheets has been demonstrated to prevent graphene agglomeration and improve the nanostructure. Conductive polymers have been the subject of considerable interest within the context of electronic device manufacturing and the development of electrochemical sensors. This is due to a number of factors, including their low cost, simple preparation, high electrical conductivity, and high compatibility with modern electronic devices. Polypyrrole (PPY), a widely used conductive polymer, has attracted attention, particularly in electrode modification. PPY exhibits excellent electrical conductivity, redox reversibility, biocompatibility, and environmental stability while also offering low production costs, making it an attractive option for use as a conductive polymer. Concurrently, the distinctive structural characteristics of graphene and its oxides render them prospective conductive fillers for conductive polymers. Consequently, the incorporation of graphene into polymers can compensate for their inherent limitations and enhance the long-term stability of sensing materials. The combination of graphene and conducting polymers represents a powerful means of preparing modified electrodes with good electrochemical properties, which have been successfully applied to the electrochemical detection of various biomolecules. For example, Oliveira et al. developed an electrochemical gene sensor based on PPY and graphene quantum dots for the detection of the PML/RARα fusion gene in childhood acute promyelocytic leukemia. As a graphene derivative, reduced graphene oxide (rGO) is similar to graphene in numerous aspects, including favourable electrical conductivity, flexibility, low cytotoxicity, hydrophilicity, a substantial surface-area-to-volume ratio, and elevated chemical resistance. These attributes render rGO an exemplary matrix for nanocomposites. Owing to the presence of hydrophilic and reactive functional groups, rGO is ideal for use in biosensors. The hydrophilic nature of rGO is instrumental in the assembly of biosensors, enabling the fabrication of sensing platforms through techniques such as drop-casting, spin-coating, ink-jet printing, and processing of electrode materials. In the present study, a “sandwich” DNA hybridisation strategy was employed to construct an electrochemical DNA sensor based on PPY-rGO composite nanomaterials. PPY-rGO nanocomplexes were initially prepared by electrochemical deposition and subsequently modified on the surface of a screen-printed carbon electrode (SPCE) to increase the conductivity of the electrode, with SARS-CoV-2 serving as the target. The PPY-rGO nanocomplexes possess a substantial specific surface area and excellent conductivity, in addition to providing many attachment sites for the subsequent electrodeposition of AuNPs by cyclic voltammetry (CV). This enables the immobilization of a greater number of single-stranded DNA (ssDNA) probes, thereby enhancing the sensitivity and specificity of the sensor for the detection of target molecules. To further improve the specificity of detection, two DNA probes were designed on the basis of a sandwich hybridization strategy. One is a specific capture DNA (CDNA) with a sulfhydryl tag, and the other is a signal DNA (SDNA) with a biotin moiety, which can bind to horseradish peroxidase-streptavidin biofunctionalized gold nanoparticles (SA-HRP-AuNPs). Hybridization of the CDNA, target DNA (tDNA), and SDNA on the electrode surface formed a sandwich structure, whereby the SA-HRP-AuNPs bound to the biotin moiety. The detection of tDNA sequences was achieved via differential pulse voltammetry (DPV), which measures the current change of the sensor in hydrogen peroxide (H2O2) and hydroquinone (HQ) as the solvent electrochemical test solution. Electrochemical characterization and sensor performance testing were performed via a convenient electrochemical workstation and PSTrace software from PalmSens (Houten, Netherlands). SPCE electrodes were
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2024103
Aberrant gene expression in cardiomyocyte has been revealed to be the fundamental essence of pathological cardiac hypertrophy. However, the detailed mechanisms are not fully understood. The underlying regulators of gene expression involved in cardiac hypertrophy remain to be further identified. Here, we report that the RNA-binding protein RNA-binding motif protein 4 (RBM4) functions as an endogenic protector that is able to fight against cardiomyocyte hypertrophy in vitro. Under pro-hypertrophic stimulation of angiotensin II (Ang II), the protein level of RBM4 in cardiomyocyte and myocardium is elevated. Knockdown of RBM4 can further aggravate cardiomyocyte hypertrophy, while over-expression of RBM4 represses cardiomyocyte hypertrophy. Mechanistically, RBM4 is localized in the nucleus and down-regulates the expression of polypyrimidine tract-binding protein 1 (PTBP1), which has been shown to aggravate cardiomyocyte hypertrophy. In addition, we suggest that the up-regulation of RBM4 in cardiomyocyte hypertrophy is caused by N6-methyladenosine (m6A). Ang II induces m6A methylation of RBM4 mRNA, which further enhances the YTH domain-containing family protein 1 (YTHDF1)-mediated translation of RBM4. Thus, our results reveal a novel pathway consisting of m6A, RBM4 and PTBP1, which is involved in cardiomyocyte hypertrophy.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2024181
MicroRNAs (miRNAs) have emerged as essential regulators that play important roles in the development of multiple systems. Recent studies have identified significant roles for miRNAs in the progression of cardiac hypertrophy. This study aims to investigate the effects of miR-133b-3p on angiotensin II (Ang II)-induced cardiac hypertrophy and apoptosis, as well as explore its underlying mechanisms. Our experimental results reveal that miR-133b-3p expression is significantly decreased in both animal and cell models of cardiac hypertrophy induced by Ang II. Overexpression of miR-133b-3p reverses the hypertrophic manifestations and apoptosis induced by Ang II. Through bioinformatics analysis and dual-luciferase reporter assays, CDIP1 (cell death inducing p53 target 1) is identified as a direct target of miR-133b-3p, and the overexpression of miR-133b-3p reduces CDIP1 expression. Additionally, CDIP1 silencing suppresses cardiomyocyte hypertrophy and apoptosis induced by Ang II. In summary, these results suggest that miR-133b-3p may serve as a potential diagnostic marker for cardiac hypertrophy and that the upregulation of miR-133b-3p inhibits cardiac hypertrophy by targeting CDIP1.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025162
Rheumatoid arthritis (RA) is an autoimmune disorder characterized by synovial hyperplasia and pannus formation, which serves as its primary pathological feature and may ultimately result in joint deformities. Lysyl oxidase (LOX) is involved in the formation and remodeling of the extracellular matrix, but its role in RA is not yet clear. This study aims to investigate the mechanism of lysyl oxidase (LOX) in synovial hyperplasia and pannus formation associated with rheumatoid arthritis (RA). Synovial, serum, and synovial fluid samples are collected from RA, osteoarthritis (OA), and knee injury patients and subsequently analyzed via HE staining, immunohistochemistry, and ELISA. Compared with those of the OA and injury groups, the RA synovium presents increased thickness, disorganized cell layers, increased microvascular density (MVD), and elevated LOX expression. Moreover, LOX levels are positively correlated with the MVD. Both synovial fluid and fibroblast-like synoviocytes (FLSs) derived from RA patients present significantly elevated concentrations of LOX. In vitro experiments reveal that LOX dose-dependently promotes the proliferation of FLSs derived from both RA patients and healthy individuals (MH7A/HFLS) by accelerating S/M-phase cell cycle progression while simultaneously stimulating angiogenesis in human umbilical vein endothelial cells (HUVECs). In contrast, the LOX inhibitor BAPN suppresses these effects. Mechanistic analysis further reveals that LOX increases the phosphorylation of the PI3K-AKT signaling pathway, an effect that is reversible by BAPN. In conclusion, LOX may induce abnormal fibroblast proliferation and endothelial neovascularization via activation of the PI3K/AKT pathway, thus aggravating synovial hyperplasia and pathological membrane formation in RA. These findings provide a theoretical foundation for the development of targeted LOX treatments for RA.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2024172
Meiosis, a process unique to germ cells, involves formation and repair of double-stranded nicks in DNA, pairing and segregation of homologous chromosomes, which ultimately achieves recombination of homologous chromosomes. Genetic abnormalities resulted from defects in meiosis are leading causes of infertility in humans. Meiotic sex chromosome inactivation (MSCI) plays a crucial role in the development of male germ cells in mammals, yet its underlying mechanisms remain poorly understood. In this study, we illustrate the predominant presence of a protein known as glucose 6 phosphatase catalyzed 3 (G6PC3) in pachytene spermatocytes, with a high concentration in the sex body (XY body), suggesting its significant involvement in male germ cell development. By employing CRISPR-Cas9 technology, we generate mice deficient in the G6pc3 gene, resulting in complete meiotic arrest at the pachytene stage in spermatocytes and are completely sterile. Additionally, we observe abnormal XY body formation and impaired MSCI in G6pc3-knockout spermatocytes. These findings underscore G6pc3 as a new essential regulator that is essential for meiotic progression. G6PC3 is involved in spermatocyte during male spermatogenesis development by the maintenance of meiosis chromosome silencing.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2023269
Previous studies have shown that puerarin plays a key role in protecting humans and animals from cardiovascular diseases. The exact mechanism of the therapeutic effect of puerarin on various cardiovascular diseases (protective effect on cardiomyocytes) is still unclear. In the present study, we identify the role of puerarin in an animal model of experimental heart failure (HF) and explore its underlying mechanisms. The HF rat model is induced by intraperitoneal injection of adriamycin (ADR), and puerarin is administered intragastrically at low, medium, and high concentrations. We demonstrate that puerarin significantly improves myocardial fibrosis and inflammatory infiltration and, as a result, improves cardiac function in ADR-induced HF rats. Mechanistically, we find for the first time that puerarin inhibits overactivated Na+/H+ exchange isoform 1 (NHE1) in HF, which may improve HF by decreasing Na+ and Ca2+ ion concentrations and attenuating mitochondrial damage caused by calcium overload; on the other hand, puerarin inhibits the activation of the p38 pathway in HF, reduces the expressions of TGF-β and proinflammatory cytokines, and suppresses myocardial fibrosis. In conclusion, our results suggest that Puerarin is an effective drug against HF and may play a protective role in the myocardium by inhibiting the activation of p38 and its downstream NHE1.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024004
SRP14 is a crucial protein subunit of the signal recognition particle (SRP), a ribonucleoprotein complex essential for co-translational translocation to the endoplasmic reticulum. During our investigation of SRP14 expression across diverse cell lines, we observe variations in its migration on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), with some cells exhibiting slower migration and others migrating faster. However, the cause of this phenomenon remains elusive. Our research rules out alternative splicing as the cause and, instead, identifies the presence of a P124A mutation in SRP14 (SRP14P124A) among the faster-migrating variants, while the slower-migrating variants lack this mutation. Subsequent ectopic expression of wild-type SRP14P124 or SRP14WT and SRP14P124A in various cell lines confirms that the P124A mutation indeed leads to faster migration of SRP14. Further mutagenesis analysis shows that the P117A and A121P mutations within the alanine-rich domain at the C-terminus of SRP14 are responsible for migration alterations on SDS-PAGE, whereas mutations outside this domain, such as P39A, Y27F, and T45A, have no such effect. Furthermore, the ectopic expression of SRP14WT and SRP14P124A yields similar outcomes in terms of SRP RNA stability, cell morphology, and cell growth, indicating that SRP14P124A represents a natural variant of SRP14 and retains comparable functionality. In conclusion, the substitution of proline for alanine in the alanine-rich tail of SRP14 results in faster migration on SDS-PAGE, but has little effect on its function.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2024158
Mechanical cues play an important role in regulating cellular activities. Cells are able to sense and respond to the mechanical cues present in the extracellular physical microenvironment via mechanotransduction, which can ultimately shape the functions and behaviors of the cells themselves as well as their microenvironments during numerous developmental, physiological and pathological processes. The development of human diseases such as cancer is generally accompanied by unique changes in the mechanical properties of cells and their physical microenvironments, and discoveries in the field of physical oncology are beginning to be translated into new therapeutic strategies for cancer. Delineating the mechanical properties of biological tissues in various dimensions from individual cells to organs is therefore fundamental for dissecting the mysteries of life and advancing human healthcare. In particular, atomic force microscopy (AFM)-based force spectroscopy has become a powerful, standard and multifunctional toolbox for characterizing the various mechanical properties of single cells at the micro/nanoscale. However, current studies of AFM-based single-cell mechanical measurements rely mainly on the experience of the experimental operator to move the AFM probe to the target cells for subsequent force measurements, which often results in a time-consuming and laborious experimental process. In addition, cell coculture has been widely used in the field of life sciences to examine intercellular interactions. Nevertheless, in current cell coculture studies, cells are commonly labelled with fluorescent molecules so that one can visually identify the specific cell types in the coculture, which can affect the behaviors of the fluorescently labelled cells. Consequently, developing a method that allows AFM to measure the mechanical properties of cells under coculture conditions in an efficient and fluorescence-independent way will significantly benefit the applications of AFM in the field of mechanobiology. Previously, we presented a method based on the combination of AFM and deep learning optical image recognition, which can precisely move the AFM probe to individual targeted cells to perform mechanical measurements under low-density co-culture conditions (nearly no contact between different cell types in the co-culture). Here, we present a study of deep learning image recognition-assisted AFM to rapidly probe the mechanical properties of single living cells grown in high-density co-culture conditions (with different cell types in contact with each other in the co-culture) without the need for fluorescent labelling. In this work, AFM experiments were performed with a commercial JPK NanoWizard AFM (Bruker, Santa Barbara, USA), which was mounted on an inverted optical microscope (Nikon, Tokyo, Japan). Three types of cells, MGC-803 (a human gastric cancer cell line), HGC-27 (a human undifferentiated gastric cancer cell line), and HMrSV5 (a human peritoneal mesothelial cell line), were used. All three types of cells were cultured in RPMI-1640 medium supplemented with 10% fetal bovine serum (FBS) and 1% penicillin-streptomycin at 37°C (5% CO2 and 95% air) in Petri dishes. During the experiments, the RPMI-1640 medium was replaced by CO2-independent Leibovitz’s L-15 medium, and the AFM experiments were performed at 37°C (the commercial AFM used here has a heater system). MGC-803 cells (stained with the DiI dye) were co-cultured with HGC-27 cells (stained with the DiO dye). Both optical bright-field images and corresponding fluorescent images of co-cultured cells were recorded. The YOLOX deep learning neural network was used for directly recognizing cell types from optical bright-field images. The fluorescent images were used to assist in the preparation of the training datasets (Supplementary Figure S1) and to verify the detection results of the deep learning image recognition model. In a previous study under low-density co-culture conditions, we reduced the complexity of the YOLOX neural network to improve the detection speed without reducing the detection accuracy. Under high-density co-culture conditions, where cell recognition becomes much more difficult, we found that reducing the complexity of the YOLOX model resulted in decreased detection accuracy. We examined the recognition performances of four YOLO series neural networks (YOLOX, YOLOv5, YOLOv7, and YOLOv8), and the experimental results revealed that the YOLOX model had the highest detection precision (89.25%) (Supplementary Table S1) and the best detection result (Supplementary Figure S2) and could meet the experimental requirements. Hence, the YOLOX neural network was used here. The AFM spherical probe (a microsphere attached to the tipless cantilever) was used in the indentation assay to measure the Young’s modulus of the cells, and the AFM single-cell probe (a living HMrSV5 cell attached to the tipless cantilever) was used in the single-cell force spectroscopy (SCFS) assay to measure the adhesion force of the cells. More experimental details (e.g., cell sample
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024014
Intrahepatic cholangiocarcinoma (ICC) accounts for approximately 15% of primary liver cancers, and the incidence rate has been increasing in recent years. Surgical resection is the best treatment for ICC, but the 5-year survival rate is less than 30%. ICC signature genes are crucial for the early diagnosis of ICC, so it is especially important to identify signature genes. The aim of this study is to screen the signature genes of ICC and find the potential target for the treatment of ICC. We find that UBA3 is highly expressed in ICC, and knockdown of UBA3 inhibits ICC proliferation, invasion and migration. Mechanistic experiments show that UBA3 promotes ICC proliferation, invasion and migration by affecting ANXA2 through the MAPK signaling pathway. UBA3 is a target of bufalin, and bufalin targeting UBA3 inhibits ICC development and progression through the MAPK signaling pathway. In conclusion, our study shows that bufalin inhibits ICC by targeting UBA3, which has emerged as a new biomarker and potential therapeutic target for ICC.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025078
Intestinal stem cells (ISCs) maintain epithelial homeostasis through continuous self-renewal and differentiation, but their regulatory mechanisms remain incompletely understood. Using a simplified culture system, we identify two novel pathways that synergistically enhance stem cell characteristics: antioxidant signaling through 2-phospho-L-ascorbic acid (pVc) and α2-adrenergic receptor (α2-AR) activation by dexmedetomidine (Dex). Mechanistic studies reveal that pVc promotes stem cell maintenance through Nrf2-mediated antioxidant responses, while α2-AR activation functions through suppression of cAMP signaling. In vivo administration of these compounds enhances intestinal epithelial renewal while maintaining proper stem cell positioning and identity. Notably, α2-AR activation promotes regeneration after radiation injury by enhancing proliferation of stem cells produced by Bmi1+ cells in the post-injury process, demonstrating therapeutic potential. These findings advance our understanding of ISC regulation and suggest new strategies for protecting intestinal integrity during injury or disease.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2024211
RNA splicing and 3′-cleavage and polyadenylation (CPA) are essential processes for the maturation of RNA. There have been extensive independent studies of these regulated processing events, including alternative splicing (AS) and alternative polyadenylation (APA). However, growing evidence suggests potential crosstalk between splicing and 3′-end processing in regulating AS or APA. Here, we first provide a brief overview of the molecular machines involved in splicing and 3′-end processing events, and then review recent studies on the functions and mechanisms of the crosstalk between the two processes. On the one hand, 3′-end processing can affect splicing, as 3′-end processing factors and CPA-generated polyA tail promote the splicing of the last intron. Beyond that, 3′-end processing factors can also influence the splicing of internal and terminal exons. Those 3′-end processing factors can also interact with different RNA-binding proteins (RBPs) to exert their effects on AS. The length of 3′ untranslated region (3′ UTR) can affect the splicing of upstream exons. On the other hand, splicing and CPA may compete within introns in generating different products. Furthermore, splicing within the 3′ UTR is a significant factor contributing to 3′ UTR diversity. Splicing also influences 3′-end processing through the actions of certain splicing factors. Interestingly, some classical RBPs play dual roles in both splicing and 3′-end processing. Finally, we discuss how long-read sequencing technologies aid in understanding the coordination of AS-APA events and envision that these findings may potentially promote the development of new strategies for disease diagnosis and treatment.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2024189
Osteoarthritis (OA) is a significant contributor to pain and disability worldwide. Pain is the main complaint of OA patients attending the clinic and has a large impact on their quality of life and economic standards. However, existing treatments for OA-related pain have not been shown to achieve good relief. The main focus is on preventing and slowing the progression of OA so that the problem of OA pain can be resolved. Pain caused by OA is complex, with the nature, location, duration, and intensity of pain changing as the disease progresses. Previous research has highlighted the role of various forms of cell death, such as apoptosis and necrosis, in the progression of pain in OA. Emerging studies have identified additional forms of novel cell death, such as pyroptosis, ferroptosis, and necroptosis that are linked to pain in OA. Different types of cell death contribute to tissue damage in OA by impacting inflammatory responses, reactive oxygen species (ROS) production, and calcium ion levels, ultimately leading to the development of pain. Evidence suggests that targeting novel types of cell death could help alleviate pain in OA patients. This review delves into the complex mechanisms of OA pain, explores the relationship between different modes of novel cell death and pain, and proposes novel cell death as a viable strategy for the treatment of these conditions, with the goal of providing scientific references for the development of future OA pain treatments and drugs.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024110
Immune checkpoint inhibitors (ICIs) targeting programmed cell death 1/programmed cell death ligand-1 (PD-1/PD-L1) have significantly prolonged the survival of advanced/metastatic patients with lung cancer. However, only a small proportion of patients can benefit from ICIs, and clinical management of the treatment process remains challenging. Glycosylation has added a new dimension to advance our understanding of tumor immunity and immunotherapy. To systematically characterize anti-PD-1/PD-L1 immunotherapy-related changes in serum glycoproteins, a series of serum samples from 12 patients with metastatic lung squamous cell carcinoma (SCC) and lung adenocarcinoma (ADC), collected before and during ICIs treatment, are firstly analyzed with mass-spectrometry-based label-free quantification method. Second, a stratification analysis is performed among anti-PD-1/PD-L1 responders and non-responders, with serum levels of glycopeptides correlated with treatment response. In addition, in an independent validation cohort, a large-scale site-specific profiling strategy based on chemical labeling is employed to confirm the unusual characteristics of IgG N-glycosylation associated with anti-PD-1/PD-L1 treatment. Unbiased label-free quantitative glycoproteomics reveals serum levels’ alterations related to anti-PD-1/PD-L1 treatment in 27 out of 337 quantified glycopeptides. The intact glycopeptide EEQFN177STYR (H3N4) corresponding to IgG4 is significantly increased during anti-PD-1/PD-L1 treatment (FC=2.65, P=0.0083) and has the highest increase in anti-PD-1/PD-L1 responders (FC=5.84, P=0.0190). Quantitative glycoproteomics based on protein purification and chemical labeling confirms this observation. Furthermore, obvious associations between the two intact glycopeptides (EEQFN177STYR (H3N4) of IgG4, EEQYN227STFR (H3N4F1) of IgG3) and response to treatment are observed, which may play a guiding role in cancer immunotherapy. Our findings could benefit future clinical disease management.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024132
Through genome-wide association studies (GWAS) and integrated expression quantitative trait locus (eQTL) analyses, numerous susceptibility genes (“eGenes”, whose expressions are significantly associated with common variants) associated with systemic lupus erythematosus (SLE) have been identified. Notably, a subset of these eGenes is correlated with disease activity. However, the precise mechanisms through which these genes contribute to the initiation and progression of the disease remain to be fully elucidated. In this investigation, we initially identify SPATS2L as an SLE eGene correlated with disease activity. eSignaling and transcriptomic analyses suggest its involvement in the type I interferon (IFN) pathway. We observe a significant increase in SPATS2L expression following type I IFN stimulation, and the expression levels are dependent on both the concentration and duration of stimulation. Furthermore, through dual-luciferase reporter assays, western blot analysis, and imaging flow cytometry, we confirm that SPATS2L positively modulates the type I IFN pathway, acting as a positive feedback regulator. Notably, siRNA-mediated intervention targeting SPATS2L, an interferon-inducible gene, in peripheral blood mononuclear cells (PBMCs) from patients with SLE reverses the activation of the interferon pathway. In conclusion, our research highlights the pivotal role of SPATS2L as a positive-feedback regulatory molecule within the type I IFN pathway. Our findings suggest that SPATS2L plays a critical role in the onset and progression of SLE and may serve as a promising target for disease activity assessment and intervention strategies.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024140
There are three isoforms of human collagen prolyl 4-hydroxylases (C-P4Hs), each of which has been reported to play an important role in regulating the progression of a variety of human cancers. By analyzing TGCA datasets on human head and neck squamous cell carcinoma (HNSC), we find that a higher expression of all three C-P4HAs (the α subunit of C-P4Hs) is a superior prognostic indicator than a higher expression of two or a single C-P4HA. Unexpectedly, some patients with higher levels of three C-P4HAs survive longer than patients whose tumors have lower expression of C-P4HAs. Therefore, there may be molecule(s) that can negate the deleterious effects of overexpressing C-P4HAs during cancer progression. By constructing a functional protein interaction network of C-P4HAs and analyzing molecules whose expressions are correlated significantly with that of C-P4HAs, we identify scribble cell polarity complex component 2 (LLGL2) as a factor that antagonizes the effects of overexpressed C-P4HAs on HNSC. Silencing of LLGL2 in the human oral squamous cell line Cal-27 upregulates the expression of occludin and increases cancer cell invasion and migration. In contrast, knocking down C-P4HA alone inhibits cell migration and invasion. Furthermore, simultaneously downregulating three C-P4HAs has more pronounced effects on inhibiting cell migration and invasion. Accordingly, high LLGL2 expression is also a marker indicating improved prognosis in patients with HNSC. These results suggest that the interplay between LLGL2 and C-P4HAs may be targeted to mitigate HNSC tumorigenesis and progression.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024061
Glioblastoma (GBM), the most aggressive and fatal brain malignancy, is largely driven by a subset of tumor cells known as cancer stem cells (CSCs). CSCs possess stem cell-like properties, including self-renewal, proliferation, and differentiation, making them pivotal for tumor initiation, invasion, metastasis, and overall tumor progression. The regulation of CSCs is primarily controlled by transcription factors (TFs) which regulate the expressions of genes involved in maintaining stemness and directing differentiation. This review aims to provide a comprehensive overview of the role of TFs in regulating CSCs in GBM. The discussion encompasses the definitions of CSCs and TFs, the significance of glioma stem cells (GSCs) in GBM, and how TFs regulate GSC self-renewal, proliferation, differentiation, and transformation. The potential for developing TF-targeted GSC therapies is also explored, along with future research directions. By understanding the regulation of GSCs by TFs, we may uncover novel diagnostic and therapeutic strategies against this devastating disease of GBM.