Biomedical Journal最新文献

{"title":"Structural Overview of GLP-1 Analogs.","authors":"Wijnand J C van der Velden, Asta F Andresen, Mette M Rosenkilde","doi":"10.1016/j.bj.2026.101037","DOIUrl":"https://doi.org/10.1016/j.bj.2026.101037","url":null,"abstract":"<p><p>Glucagon-like peptide-1 (GLP-1) analogs exert potent metabolic effects through structural features that govern receptor engagement, signaling, and pharmacokinetics. Key structural determinants include N-terminal modifications that confer resistance to dipeptidyl peptidase-4 degradation, as well as C-terminal and backbone elements that stabilize peptide helicity and enhance GLP-1 receptor affinity. Lipidation and albumin-binding strategies prolong systemic exposure by increasing circulating half-life, forming the basis of long-acting agents such as liraglutide and semaglutide. Structural variation further modulates signaling bias between G protein pathways and β-arrestin recruitment, potentially influencing therapeutic efficacy. Emerging multi-receptor agonists extend these principles across incretin receptor families and are increasingly supported by computational approaches to peptide optimization. Collectively, these advances illustrate how rational design drives the development of next-generation incretin therapeutics. This review synthesizes current insights into structural determinants of GLP-1 analogs and highlights future directions in the field.</p>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":" ","pages":"101037"},"PeriodicalIF":6.3,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148944229","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":"KRAS Expression Complements Genomic Profiling in Identifying Therapeutic Vulnerability in Gastric Cancer.","authors":"Yu-Lun Chen, Wei-Ching Chen, Ta-Sen Yeh, Hsing-Hua Ho, Tse-Ching Chen, Wen-Ching Wang","doi":"10.1016/j.bj.2026.101036","DOIUrl":"https://doi.org/10.1016/j.bj.2026.101036","url":null,"abstract":"<p><strong>Background: </strong>Gastric cancer (GC) remains a major therapeutic challenge. Although alterations in the RAS pathway occur in over 50% of tumors, only a limited proportion are clinically actionable. We investigated whether KRAS expression complements genomic profiling for patient stratification and therapeutic vulnerability in GC.</p><p><strong>Methods: </strong>Comprehensive genomic profiling was performed in 19 Taiwanese GC patients and compared with TCGA-STAD data (n = 434). KRAS mRNA expression and overall survival were evaluated by meta-analysis of 13 independent cohorts (n = 2,521). Protein-level validation was performed by immunohistochemistry in an independent cohort (n = 121). Functional KRAS dependency and response to combined MEK/SHP2 inhibition were assessed in eight GC cell lines.</p><p><strong>Results: </strong>KRAS amplification was entirely contained within the KRAS-high population, whereas most KRAS-high tumors lacked detectable amplification. High KRAS expression was associated with poorer overall survival (HR 1.23, p = 0.001) and remained an independent prognostic factor after multivariable adjustment (adjusted HR 1.24, p = 0.003). Protein-level analysis showed a concordant trend. KRAS expression correlated strongly with functional dependency (R² = 0.88, p = 0.005), was enriched in MSI and CIN subtypes, and identified cell lines with enhanced sensitivity to combined MEK/SHP2 inhibition.</p><p><strong>Conclusions: </strong>KRAS expression complements genomic profiling by identifying biologically relevant KRAS-dependent GCs beyond mutation or amplification alone. Integrating expression-based stratification with genomic profiling may improve patient selection for RAS pathway-directed combination therapies.</p>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":" ","pages":"101036"},"PeriodicalIF":6.3,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148886403","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":"Age-stratified gut microbiome variation in a Taiwanese cohort.","authors":"Yuan-Ming Yeh, Hao-Tsai Cheng, Chien-Chang Chen, Chia-Jung Kuo, Cheng-Tang Chiu, Puo-Hsien Le, Cheng-Hsun Chiu","doi":"10.1016/j.bj.2026.101035","DOIUrl":"https://doi.org/10.1016/j.bj.2026.101035","url":null,"abstract":"","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":" ","pages":"101035"},"PeriodicalIF":6.3,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148824649","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":"Adipocyte-specific MICU1 deficiency impairs memory and compromises hippocampal integrity in adult male mice.","authors":"Wei-Hsuan Wang, Pei-Jane Tsai, Ching-Han Lin, Hao-Yeh Tsai, Yau-Sheng Tsai, Pei-Chun Chen","doi":"10.1016/j.bj.2026.101034","DOIUrl":"https://doi.org/10.1016/j.bj.2026.101034","url":null,"abstract":"<p><p>Peripheral metabolic stress is increasingly implicated in cognitive decline, but whether adipocyte-specific perturbation of mitochondrial calcium regulation is associated with hippocampal vulnerability remains unclear. Here, we used adipocyte-specific mitochondrial calcium uptake 1 knockout mice (aMICU1 KO) to examine whether adipocyte MICU1 deficiency is accompanied by memory-related behavioral changes and hippocampal pathology. aMICU1 KO mice showed no significant changes in body weight or adipose tissue mass but exhibited impaired spontaneous alternation in the Y-maze and reduced novel object recognition, whereas locomotor activity, anxiety-like behavior, impulsivity, and rotarod performance were not significantly altered. Histological and molecular analyses revealed reduced Nissl-positive cell counts in the dentate gyrus and CA regions, increased TUNEL staining, elevated cleaved caspase-3, and reduced BrdU+ and BrdU+/DCX+ cell populations. Hippocampal MICU1 expression was unchanged, supporting a non-cell-autonomous association rather than direct brain MICU1 loss. Adipose tissue and plasma analyses identified increased GDF15 as a prominent stress-associated circulating factor; however, hippocampal GFRAL/RET expression and downstream AKT/ERK phosphorylation were not robustly activated. Thus, GDF15 should be interpreted as a systemic stress-associated marker rather than a proven causal mediator. Together, these findings identify adipocyte MICU1 deficiency as a peripheral perturbation associated with hippocampal vulnerability and memory impairment, and they provide a foundation for future studies testing the adipocyte mitochondrial mechanisms and peripheral mediators that link adipose dysfunction to brain pathology.</p>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":" ","pages":"101034"},"PeriodicalIF":6.3,"publicationDate":"2026-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148787876","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":"Longitudinal Changes in Clonal Distribution and Fluoroquinolone Resistance of Ocular MRSA.","authors":"Ching-Hsi Hsiao, Eugene Yu-Chuan Kang, Ya-Tung Liu, Hung-Chi Chen, Lung-Kun Yeh, David H K Ma, Kuo-Hsuan Hung, Yhu-Chering Huang","doi":"10.1016/j.bj.2026.101033","DOIUrl":"https://doi.org/10.1016/j.bj.2026.101033","url":null,"abstract":"<p><strong>Background: </strong>Methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of ocular infections, with evolving molecular epidemiology observed in systemic infections in Taiwan. However, longitudinal data on clonal distribution and antibiotic susceptibility in ocular MRSA isolates remain limited.</p><p><strong>Material and methods: </strong>Patients with culture-proven S. aureus ocular infection at Chang Gung Memorial Hospital between 2013 and 2022 were included. MRSA isolates were characterized by pulsed-field gel electrophoresis, multilocus sequence typing, and staphylococcal cassette chromosome mec typing, and Panton-Valentine leucocidin genes detection. Antibiotic susceptibility was examined using disk diffusion method and E-test. Temporal trends were analyzed using chi-square tests for trend.</p><p><strong>Results: </strong>A total of 154 MRSA ocular isolates were identified. The predominant clone complex (CC) was CC59 (80/154, 52.0%), followed by CC8 (30/154, 19.5%) and CC45 (25/154, 16.2%). Over the decade, CC59 declined while CC8 increased significantly (P = 0.005 and P = 0.002, respectively), paralleling nationwide systemic MRSA trends. CC8 isolates were more frequently associated with eyelid disorders than CC59 (50.0% vs 28.8%; P = 0.045). CC59 isolates remained highly susceptible to fluoroquinolones (> 95%), while CC8 demonstrated marked resistance (≤ 11% susceptible; P < 0.0001). All isolates were susceptible to vancomycin and teicoplanin.</p><p><strong>Conclusions: </strong>Ocular MRSA infections in Taiwan demonstrate longitudinal changes in clonal distribution, characterized by declining CC59 and increasing CC8, and a concurrent increase in fluoroquinolone-resistant CC8. This evolution may compromise fluoroquinolone-based empirical therapy, a cornerstone of first-line treatment for ocular infections, and highlights the importance of continued molecular surveillance.</p>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":" ","pages":"101033"},"PeriodicalIF":6.3,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148757364","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":"Baseline imbalances in a real-world study of TKI plus radiotherapy for HCC with PVTT: Implications for interpreting survival outcomes.","authors":"Siyuan Zhu, Peiru Zhang","doi":"10.1016/j.bj.2026.101022","DOIUrl":"https://doi.org/10.1016/j.bj.2026.101022","url":null,"abstract":"","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":" ","pages":"101022"},"PeriodicalIF":6.3,"publicationDate":"2026-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148683393","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":"Gastric microbiota composition and its association with rescue eradication outcomes in refractory Helicobacter pylori infection.","authors":"Chia-Jung Kuo, Ngoc-Niem Bui, Yuan-Ming Yeh, Cheng-Yu Lin, Shih-Yu Wu, Wey-Ran Lin, Ming-Ling Chang, Cheng-Tang Chiu, Cheng-Hsun Chiu, Chih-Ho Lai","doi":"10.1016/j.bj.2026.101023","DOIUrl":"https://doi.org/10.1016/j.bj.2026.101023","url":null,"abstract":"<p><strong>Background: </strong>The relationship between gastric microbiota composition, Helicobacter pylori infection, and eradication outcomes remains unclear. This study aims to explore the association of gastric microbiota composition among patients with refractory H. pylori infection with the outcomes of rescue therapy.</p><p><strong>Material and methods: </strong>Patients who failed to respond to second- or third-line eradication therapies were prospectively enrolled. The composition of the gastric microbiota was analyzed using 16S rRNA gene sequencing prior to rescue therapy. The eradication outcomes were confirmed using the [¹³C]-urea breath test.</p><p><strong>Results: </strong>Among 1,590 screened participants, 23 patients with refractory H. pylori infection who underwent rescue therapy based on antimicrobial susceptibility testing were enrolled. The alpha diversity did not differ between success and failure groups; however, the beta diversity analysis revealed a distinct microbial composition. The success group was enriched in Streptococcus, Neisseria, Cutibacterium, and Staphylococcus, with two significant species, Streptococcus mitis and Streptococcus cristatus. In contrast, Prevotella colorans was enriched in the failure group.</p><p><strong>Conclusions: </strong>Distinct gastric microbiota signatures were associated with treatment outcomes in patients with refractory H. pylori infection. These findings provide insights that may facilitate the development of microbiota-based diagnostics and interventions to improve eradication success.</p>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":" ","pages":"101023"},"PeriodicalIF":6.3,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148677097","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":"Distinguishing true from false idiopathic pulmonary fibrosis: Progress in biomarkers for early identification of rheumatoid arthritis.","authors":"Yu Su, Xi Qin, Luhan Guo, Hulei Zhao","doi":"10.1016/j.bj.2026.101021","DOIUrl":"https://doi.org/10.1016/j.bj.2026.101021","url":null,"abstract":"<p><strong>Background: </strong>Patients initially diagnosed with idiopathic pulmonary fibrosis (IPF) have an underlying risk of being in a preclinical phase of rheumatoid arthritis (RA), but effective biomarkers for early identification of this transition are lacking.</p><p><strong>Objective: </strong>This review aims to comprehensively summarize predictive markers for future RA in patients meeting IPF diagnostic criteria, supporting early risk stratification and pre-arthritic intervention.</p><p><strong>Methods: </strong>Using \"idiopathic pulmonary fibrosis\", \"rheumatoid arthritis\", \"predictive markers\", \"markers\", \"clinical research\", \"in vitro experiments\", \"mechanism\", and their combinations as keywords, a structured literature search was conducted in the PubMed database for relevant literature from 2001 to 2025.</p><p><strong>Results: </strong>The propensity for RA to develop in patients initially meeting IPF diagnostic criteria has a multi-dimensional basis: genetic susceptibility provides the background; immune dysregulation mediates the dissemination of autoimmunity from a pulmonary origin to systemic involvement; inflammatory markers reflect disease activity; environmental exposure acts as an external trigger. Based on these mechanisms, four predictive marker types were identified: genetic susceptibility, immune activation, inflammatory injury, and environmental exposure. However, current studies are mainly cross-sectional and retrospective, lacking prospective validation of predictive efficacy; combined application strategies, clinical value and microbiome-based indicators all require further clinical verification.</p><p><strong>Conclusion: </strong>This review identified four early-warning markers-genetic susceptibility, immune activation, inflammatory injury, and environmental exposure-that may signal future RA in patients initially presenting with IPF. These findings support shifting from passive diagnosis to active screening for earlier intervention. Future research should focus on multi-dimensional prediction models, prospective cohort studies, and ultimately achieving early identification and intervention for this hidden RA-prone population.</p>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":" ","pages":"101021"},"PeriodicalIF":6.3,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148668269","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":"Low-energy extracorporeal shock wave therapy is associated with reduced inflammation and fibrosis in an E₂-induced rat model of endometriosis and remains effective under menopause-mimicking conditions.","authors":"Kuo-Chung Lan, Yin-Hua Cheng, Cheng-Rung Huang, Pei-Ling Weng, Yung-Chiao Chang, Jai-Hong Cheng","doi":"10.1016/j.bj.2026.101024","DOIUrl":"https://doi.org/10.1016/j.bj.2026.101024","url":null,"abstract":"<p><strong>Background: </strong>Endometriosis is an estrogen-dependent inflammatory disorder marked by ectopic lesions, chronic pelvic inflammation, and frequent recurrence. Extracorporeal shock wave therapy (ESWT) is a non-invasive modality with anti-inflammatory and regenerative potential, but its efficacy under varying estrogen conditions remains unclear.</p><p><strong>Methods: </strong>Endometriosis-like lesions were induced in female rats by suturing uterine fragments to the peritoneum, followed by daily 17β-estradiol (E₂) or PBS for 28 days. Sprague-Dawley rats were assigned to control, E₂, E₂ + ESWT (0.1 or 0.25 mJ/mm²), or ovariectomy (OVX) + ESWT groups. ESWT was applied twice weekly for three weeks. Body weight, food intake, lesion morphology, histology, and serum E₂ were assessed. Inflammatory and fibrotic markers were analyzed as follows: transforming growth factor beta (TGF-β) and tumor necrosis factor-alpha (TNF-α) were evaluated by both immunohistochemistry (IHC) and quantitative real-time RT-PCR (qRT-PCR), whereas interleukin (IL)-6, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), cyclooxygenase (COX)-2, vascular endothelial growth factor (VEGF), cytokeratin (CK)-18, superoxide dismutase (SOD), inducible nitric oxide synthase (iNOS), and hypoxia-inducible factor-1 alpha (HIF-1α) were assessed by qRT-PCR only.</p><p><strong>Results: </strong>E₂ reduced body weight and food intake and induced cystic peritoneal lesions with upregulated fibrotic and inflammatory markers. ESWT at both energy levels significantly reduced lesion size, cystic formation, the number of endometrial glands (hematoxylin-eosin, H&E staining), fibrosis area ratio (Masson trichrome staining), and expression of fibrosis-, inflammation- oxidative stress-, and hypoxia-related genes and proteins regardless of ovarian status. OVX combined with ESWT produced comparable or slightly enhanced reductions in several markers. ESWT did not alter systemic E₂ levels, whereas OVX resulted in reduced serum estrogen levels.</p><p><strong>Conclusion: </strong>Low-energy ESWT attenuated E₂-induced endometriotic lesions, accompanied by reductions in proliferation, inflammation, and fibrosis, without altering circulating estrogen levels. These effects were also observed under menopause-mimicking conditions with controlled estrogen exposure. These findings suggest that ESWT may serve as a complementary non-hormonal adjunctive approach and may provide a useful experimental framework for future mechanistic and preclinical studies.</p>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":" ","pages":"101024"},"PeriodicalIF":6.3,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148668299","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":"Fu's subcutaneous needling therapy significantly enhances pain relief in sciatica rats by promoting mitochondrial autophagy","authors":"Yarong Sun,&nbsp;Zhenquan Wei,&nbsp;Po-En Chiu,&nbsp;Ruolin Xie,&nbsp;Jiaqi Li,&nbsp;Yunhua Zang,&nbsp;Li-Wei Chou","doi":"10.1016/j.bj.2025.100927","DOIUrl":"10.1016/j.bj.2025.100927","url":null,"abstract":"<div><h3>Background</h3><div>Mitochondrial autophagy is linked to neuropathic pain. This study explores how Fu's subcutaneous needling (FSN) affects sciatica via mitochondrial autophagy modulation.</div></div><div><h3>Methods</h3><div>40 male SD rats were divided into four groups. Except for the control group (COT), the other three groups were utilized to establish a chronic sciatic nerve injury model. Mechanical pain thresholds were measured. FSN and acupuncture (ACP) groups received treatments every other day for four sessions. Mitochondrial quantity and morphology were examined under a transmission electron microscope, and the expression levels of PINK1, Parkin, and P62 proteins in the rat pyriform were analyzed through immunohistochemistry and immunofluorescence. Furthermore, the levels of TNF-α and IL-6 inflammatory factors in the serum of all groups were measured using ELISA, and the expression levels of midbrain opioid receptors κ and μ mRNA in each group of rats were determined via qPCR.</div></div><div><h3>Results</h3><div>FSN and ACP groups showed higher pain thresholds than the model group from the second intervention. FSN outperformed ACP after the fourth intervention. Transmission electron microscope showed improved mitochondrial morphology in FSN and ACP groups, with FSN showing better morphology. FSN upregulated PINK1/Parkin and downregulated P62. FSN also reduced TNF-α and IL-6 levels.</div></div><div><h3>Conclusions</h3><div>FSN alleviates neuropathic pain by enhancing mitochondrial autophagy, restoring mitochondrial dynamics, and reducing inflammation. It shows promise as a therapeutic strategy for neuropathic pain.</div></div>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":"49 4","pages":"Article 100927"},"PeriodicalIF":6.3,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145430382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}