Biomedical Journal最新文献

{"title":"Co-radiotherapy with tyrosine kinase inhibitors might benefit survival in hepatoma patients with portal vein tumor thrombosis","authors":"Hui-Ling Huang ,&nbsp;Wei-Ming Lin ,&nbsp;Chia-Hsuan Lai ,&nbsp;Te-Sheng Chang ,&nbsp;Sheng-Nan Lu","doi":"10.1016/j.bj.2025.100904","DOIUrl":"10.1016/j.bj.2025.100904","url":null,"abstract":"<div><h3>Background</h3><div>Hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) is associated with a poor prognosis, and current treatment options yield suboptimal results. This article aims to share our treatment outcomes for PVTT using tyrosine kinase inhibitors (TKIs), radiation therapy (RT), and their combination.</div></div><div><h3>Methods</h3><div>From 2010 to 2021, a total of 160 Child-Pugh class A HCC patients with PVTT, but without extrahepatic spread, were enrolled. Among them, 26, 10, 81, and 43 patients underwent no treatment, RT, TKIs, and combination therapy, respectively.</div></div><div><h3>Results</h3><div>Compared to the no treatment group (median survival: 2 months), the RT group (4.5 months, <em>p</em> = 0.034), TKIs group (5.0 months, <em>p</em> = 0.0017), and combination group (15.0 months, <em>p</em> &lt; 0.001) all demonstrated a survival benefit. The multivariate Cox model showed adjusted hazard ratios and 95 % confidence intervals of 0.35 (0.16–0.78), 0.40 (0.25–0.63) and 0.26 (0.15–0.44) for RT, TKIs, combination groups, respectively. From clinical observation of patients who survived for two years, we found that 20 % of RT patients achieved good local control, and the RT group had longer durations of TKI use.</div></div><div><h3>Conclusions</h3><div>In this series, 26.9 % (43/160) of HCC patients with PVTT underwent combination treatment with TKIs and RT, achieving a median survival of 15.0 months. The contributions of RT were 20 % disease control rate and may extend the duration of TKIs use. Therefore, all candidates without contraindications should be considered for combination treatment.</div></div>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":"49 2","pages":"Article 100904"},"PeriodicalIF":4.4,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144858825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long non-coding RNAs as modulators of metabolic reprogramming for endogenous heart regeneration: Mechanisms and therapeutic potential","authors":"Xueping Wu ,&nbsp;Yehui Lv ,&nbsp;Zhihong Li ,&nbsp;Zhifang Yang","doi":"10.1016/j.bj.2025.100914","DOIUrl":"10.1016/j.bj.2025.100914","url":null,"abstract":"<div><div>Myocardial infarction (MI) is one of the leading causes of death worldwide, with its high incidence and mortality posing a significant threat to human health. Despite some progress in the treatment of myocardial infarction, mortality rates remain alarmingly high. Adult mammals have limited myocardial regenerative capacity, and extensive cell death caused by myocardial ischemia severely impairs cardiac function, leading to heart failure or death. In contrast, neonatal myocardium possesses a robust regenerative ability, which gradually diminishes after birth. The loss of cardiomyocyte regenerative capacity is often accompanied by a shift in energy metabolism—from reliance on glucose (glycolysis) to fatty acid oxidation. This metabolic reprogramming significantly impacts CM proliferation. Long non-coding RNAs (lncRNAs) orchestrate cardiac regeneration through epigenetic control (e.g., Bvht/PRC2-mediated silencing), metabolic reprogramming (e.g., GATA6-AS1 suppression of FAO), and miRNA sponging (e.g., CAREL sequestration of miR-296). However, our understanding of the metabolic determinants and pathways that promote myocardial regeneration after myocardial infarction is still insufficient. This review investigates the interplay between lncRNAs and metabolic reprogramming in cardiovascular function, aiming to identify novel therapeutic targets and strategies to enhance myocardial regeneration post-MI.</div></div>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":"49 2","pages":"Article 100914"},"PeriodicalIF":4.4,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New concepts for glioblastoma vaccine immunotherapy.","authors":"Mariam Shallak, Amruth K B Shaik, Andrea Gatta, Mattia Volpi, Roberto S Accolla, Greta Forlani","doi":"10.1016/j.bj.2026.100974","DOIUrl":"https://doi.org/10.1016/j.bj.2026.100974","url":null,"abstract":"<p><strong>Background: </strong>Glioblastoma remains one of the most lethal malignancies, characterized by rapid recurrence, profound intratumoral heterogeneity, and a highly immunosuppressive microenvironment. Among immunotherapeutic strategies, peptide-based vaccines have attracted attention for their safety, specificity, and capacity to elicit tumor-directed T cell responses. Over the past two decades, several platforms targeting tumor-associated or tumor-specific antigens, including EGFRvIII, WT1, and survivin, have advanced into clinical trials. While early-phase studies demonstrated immunogenicity and occasional survival benefits, phase III trials have largely failed to confirm durable efficacy, underscoring the challenges posed by the ongoing complexity of tumor evasion mechanisms among which down regulation of MHC (HLA) expression in tumor cells, lack or reduced tumor antigen expression and a suppressive tumor microenvironment certainly play a role.</p><p><strong>Main body: </strong>As far as tumor antigens, recent insights also question the centrality of neoantigens, highlighting instead the immunogenicity of shared tumor-associated antigens, which may provide a more reliable foundation for broadly applicable vaccines in GBM. A major barrier to efficacy remains impaired antigen presentation, particularly the downregulation of MHC-II pathways. In this context, strategies leveraging the transcriptional activator CIITA to restore MHC-II expression hold promise both for reprogramming GBM cells into effective antigen-presenting cells and for the isolation of new families of MHC class II-bound peptides relevant for the triggering of tumor-specific CD4+ T cells.</p><p><strong>Conclusion: </strong>This new approach could pave the way for next-generation peptide vaccines, particularly when integrated with combinatorial modalities such as checkpoint inhibitors, myeloid-targeted therapies, or oncolytic viruses.</p>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":" ","pages":"100974"},"PeriodicalIF":4.4,"publicationDate":"2026-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147580091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glibenclamide attenuates neuronal pyroptosis by modulating K_ATP channels in the hippocampus of palmitic acid-induced lipotoxic mice.","authors":"Chung-Lin Chen, Liang-Chu Chang, Chao-Yu Chen, Yen-Shuo Lai, Pei-Chun Chen, Ching-Han Lin","doi":"10.1016/j.bj.2026.100972","DOIUrl":"https://doi.org/10.1016/j.bj.2026.100972","url":null,"abstract":"<p><p>Metabolic lipotoxicity contributes to neuroinflammation and cognitive dysfunction, yet the cellular mechanisms linking saturated fatty acids to hippocampal injury remain incompletely understood. In this study, we investigated whether glibenclamide (GB), a clinically used ATP-sensitive potassium (K_ATP) channel inhibitor, modulates hippocampal inflammatory responses induced by palmitic acid (PA). Male C57BL/6N mice were subjected to chronic PA injections with or without GB treatment for four weeks. Behavioral tests, histological analyses, and molecular assays were performed to evaluate hippocampal function and inflammatory signaling. Chronic PA exposure impaired recognition memory and was associated with neuronal apoptosis, microglial activation, and lipid accumulation in the hippocampus. PA treatment also increased the expression of inflammasome-associated markers, including NLRP3, caspase-1, gasdermin D (GSDMD), and IL-1β, together with elevated levels of pro-inflammatory cytokines (IL-6, MCP-1, TNF-α). GB treatment attenuated these changes and reduced markers of inflammasome activation in both hippocampal tissue and PA-treated BV2 microglial cells. Immunofluorescence analysis further revealed spatial proximity between SUR1/K_ATP channel components and GSDMD at the microglial cell surface following PA exposure. These findings indicate that PA-induced lipotoxic stress promotes microglial activation and inflammasome-associated pyroptotic signaling in the hippocampus. GB treatment mitigates these inflammatory responses, suggesting that modulation of microglial signaling pathways may represent a potential strategy for metabolic disorder-associated cognitive dysfunction.</p>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":" ","pages":"100972"},"PeriodicalIF":4.4,"publicationDate":"2026-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147572118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Response to: \"Clearing the Fog, But Not the Entire Picture: Elastase Pretreatment for ALK FISH in Lung Cancer\".","authors":"Sheng-Chi Hsu, Tsai-Hsien Hung, Hsiao-Chun Wu, Kwai-Fong Ng, Tse-Ching Chen","doi":"10.1016/j.bj.2026.100973","DOIUrl":"https://doi.org/10.1016/j.bj.2026.100973","url":null,"abstract":"","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":" ","pages":"100973"},"PeriodicalIF":4.4,"publicationDate":"2026-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147572146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Developmental Origins and Environmental Determinants of Cardiovascular-Kidney-Metabolic Syndrome: A Pediatric Precision Prevention Perspective.","authors":"You-Lin Tain, Chien-Ning Hsu","doi":"10.1016/j.bj.2026.100970","DOIUrl":"https://doi.org/10.1016/j.bj.2026.100970","url":null,"abstract":"<p><p>Cardiovascular-Kidney-Metabolic Syndrome (CKMS), formally defined by the American Heart Association in 2023, emphasizes the interconnections among chronic kidney disease, cardiovascular disease, obesity, and diabetes. Although CKMS typically manifests in adulthood, accumulating evidence indicates that vulnerability is established early in life through developmental programming shaped by maternal, perinatal, and early-childhood exposures. This review summarizes the developmental origins, environmental determinants, and mechanistic pathways of CKMS, with a particular emphasis on kidney programming and pediatric precision prevention. Recent nationally representative data indicate that CKMS risk-stage (stage ≥1) affects approximately 90% of U.S. adults and 40% of adolescents, highlighting the extensive population burden long before overt clinical disease develops, yet kidney health remains underrecognized within cardiometabolic risk assessment. In children, early metabolic disruption, excess adiposity, and subclinical cardiovascular dysfunction interact with structural or developmental renal vulnerability to accelerate CKD progression and amplify lifelong risk. Evidence from the Developmental Origins of Health and Disease framework demonstrates that maternal malnutrition, metabolic disease, toxicant exposures, preterm birth, and perinatal complications permanently alter nephron endowment, vascular function, and metabolic regulation. Animal studies reveal convergent mechanisms-including oxidative stress, aberrant renin-angiotensin activity, epigenetic modifications, gut microbiota dysbiosis, and sex-specific responses-that predispose offspring to CKMS and highlight targets for early-life reprogramming. Prevention should begin with maternal health and the first 1000 days, incorporating nutritional and lifestyle interventions, early screening for obesity, hypertension, and dyslipidemia, and emerging microbiome- or antioxidant-targeted therapies. Advances in multi-omics, digital health, and AI-enabled monitoring facilitate early risk stratification and precision prevention, although pediatric-specific guidelines remain limited. Viewed through a life-course lens, CKMS represents a gradual, self-reinforcing process rooted in developmental programming and environmental exposures. Integrating maternal and pediatric interventions within a life-course precision prevention framework provides a roadmap to disrupt disease trajectories, reduce intergenerational risk, and promote lifelong cardiovascular, kidney, and metabolic health.</p>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":" ","pages":"100970"},"PeriodicalIF":4.4,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147526103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clearing the Fog, But Not the Entire Picture: Elastase Pretreatment for ALK FISH in Lung Cancer.","authors":"Xiaoman Liu, Jiachun Xu","doi":"10.1016/j.bj.2026.100971","DOIUrl":"https://doi.org/10.1016/j.bj.2026.100971","url":null,"abstract":"","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":" ","pages":"100971"},"PeriodicalIF":4.4,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147526078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Steatosis Paradox: Unraveling Pathways of Suppressive Effect of Hepatic Steatosis on Hepatitis B Virus.","authors":"Shang-Chin Huang, Jia-Horng Kao","doi":"10.1016/j.bj.2026.100969","DOIUrl":"https://doi.org/10.1016/j.bj.2026.100969","url":null,"abstract":"<p><p>The global intersection of chronic hepatitis B (CHB) and metabolic dysfunction-associated steatotic liver disease (MASLD) has revealed an intriguing clinical paradox: hepatic steatosis is frequently associated with lower hepatitis B virus (HBV) viral loads, higher rates of HBsAg seroclearance, and even favorable clinical outcomes. Accumulating data suggest that lipid accumulation transforms hepatocytes into a hostile microenvironment for HBV through at least four pathways, including immune modulation, metabolic reprogramming, endoplasmic reticulum stress, and impaired autophagy. Deciphering these molecular pathways not only explains the unique natural history of CHB patients with concurrent MASLD but also highlights novel therapeutic targets such as selective modulators of cellular stress that could complement existing antivirals or immune enhancers to facilitate functional cure. In this review, the current evidence regarding the cellular mechanisms underlying the suppressive effect of steatosis on HBV is summarized, providing a translational roadmap for exploiting these virus-host metabolic interactions to develop next-generation, novel host-targeting therapies against HBV.</p>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":" ","pages":"100969"},"PeriodicalIF":4.4,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147526112","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circulating Short-Chain Fatty Acid (SCFA) Profiles as a Biomarker of Gut-Brain Axis Dysfunction: A Meta-Analysis for the SCFA Signature in Major Depression.","authors":"Quang Le Do, Ikbal Andrian Malau, Hoan Thi Nguyen, Jiaming Liu, Jane Pei-Chen Chang, Kuan-Pin Su","doi":"10.1016/j.bj.2026.100968","DOIUrl":"https://doi.org/10.1016/j.bj.2026.100968","url":null,"abstract":"<p><strong>Background: </strong>Major Depressive Disorder (MDD) is increasingly viewed through the lens of the neuroinflammatory hypothesis and gut-brain axis dysfunction. Short-Chain Fatty Acids (SCFAs), the primary metabolites produced by the gut microbiota, are vital signaling molecules that maintain intestinal barrier integrity, modulate peripheral immunity, and influence microglial function. While individual studies suggest altered SCFAs levels in MDD, a definitive, quantitative synthesis establishing a robust biomarker signature is currently lacking. This meta-analysis aimed to precisely characterize the signature of SCFAs (acetic, propionic, butyric, and isobutyric acid) in MDD patients compared to healthy controls.</p><p><strong>Methods: </strong>We systematically searched major databases across PubMed, Embase, and Web of Science databases for studies quantifying SCFAs levels up to September 15, 2025. Studies examining SCFAs levels in depressed patients and depressive-like murine models, as well as studies investigating SCFAs interventions for depressive-like behavior, were selected for synthesis. Risk of bias was evaluated using the Newcastle-Ottawa Scale. The effect sizes were synthesized using a random-effects model and presented as standardized mean differences.</p><p><strong>Results: </strong>Eight human and 52 murine studies were included in the meta-analyses. Depressed patients showed significantly lower concentrations in blood (plasma and serum) of propionic (SMD = -0.60, p-value = 0.007), butyric (SMD = -0.50, p-value = 0.006), isobutyric (SMD = -0.72, p-value = 0.020), valeric (SMD = -0.43, p-value = 0.040) and isovaleric acids (SMD = -0.75, p-value = 0.002). Secondary analysis of MDD patients confirmed consistent reductions. High heterogeneity was observed. In murine models, SCFAs depletion was frequently observed, while supplementation improved depressive-like behaviors.</p><p><strong>Conclusion: </strong>MDD is characterized by a significant, quantifiable deficit in the circulating SCFAs metabolome, which provides strong empirical validation for the gut-brain axis hypothesis in depression. We advocate for the investigation of SCFAs as novel, measurable peripheral biomarkers and targeted therapeutic agents (e.g., butyrate supplementation) for precision nutritional psychiatry.</p>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":" ","pages":"100968"},"PeriodicalIF":4.4,"publicationDate":"2026-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147497673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CRISPR-Cas9-mediated elimination of plasmid-borne carbapenemase genes restores ertapenem susceptibility in clinical Klebsiella pneumoniae isolates.","authors":"Shu-Fang Kuo, Tsung-Yu Huang, Chih-Yi Lee, Fang-Ju Chen, Chen-Hsiang Lee","doi":"10.1016/j.bj.2026.100966","DOIUrl":"https://doi.org/10.1016/j.bj.2026.100966","url":null,"abstract":"<p><strong>Background: </strong>Carbapenem-resistant Klebsiella pneumoniae (CRKP) represents a critical public health threat due to its broad-spectrum antimicrobial resistance and capacity for horizontal gene transfer.</p><p><strong>Methods: </strong>Three clinical CRKP isolates, each carrying one of the three major classes of carbapenemase as class A (bla_KPC), class B (bla_NDM), and class D (bla_OXA) were selected. A CRISPR/Cas9-based system (pCasKP-pSGKP) was employed to target carbapenem resistance genes in these strains (KP21040 with bla_OXA-181, KP4-78 with bla_NDM-1, and KP5-4 with bla_KPC-2).</p><p><strong>Results: </strong>CRISPR/Cas9-mediated editing led to partial reduction or complete loss of resistance plasmids, as evidenced by S1 nuclease-pulsed-field gel electrophoresis. This plasmid elimination correlated with a marked restoration of susceptibility to ertapenem, showing a greater than 64-fold reduction in minimum inhibitory concentrations (MICs) across all strains. In KP21040, MICs for ertapenem and levofloxacin decreased to 0.006 μg/mL and 0.125 μg/mL, respectively. Whole-genome analysis revealed that bla_OXA-181 was flanked by insertion sequence (IS)26 elements, which mediated homologous recombination upon CRISPR-induced double-strand breaks, resulting in excision of a ∼15 kb segment including bla_OXA-181 and qnrS1. These findings suggest that ISs may enhance CRISPR efficacy by promoting recombination-driven deletion. Moreover, the complete removal of all three resistance plasmids was observed in the KP5-4 strain harboring bla_KPC-2.</p><p><strong>Conclusion: </strong>This study demonstrates that CRISPR/Cas9-based genome editing can eliminate plasmid-encoded carbapenemase genes in clinical CRKP isolates and, in specific genetic contexts, facilitate the concurrent removal of associated quinolone resistance determinants. These findings support CRISPR-based genome editing as a proof-of-concept strategy for addressing plasmid-mediated multidrug resistance in Gram-negative pathogens.</p>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":" ","pages":"100966"},"PeriodicalIF":4.4,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147479603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}