Biomedical Journal最新文献

{"title":"Cellular membranes as contested territories in the virus-host conflict.","authors":"Jim Zoladek, Sébastien Nisole","doi":"10.1016/j.bj.2026.101058","DOIUrl":"https://doi.org/10.1016/j.bj.2026.101058","url":null,"abstract":"<p><p>Cellular membranes emerge as contested territories in the virus-host conflict. Many viruses depend on host membrane systems throughout their life cycle for entry, replication, assembly, and egress. At the same time, innate immune sensing and interferon (IFN) signaling are themselves organized around membrane-associated platforms. Cellular membranes therefore function both as essential substrates for viral replication and as central sites of antiviral defense. In this review, we examine how IFN-induced responses reshape membrane biology through coordinated changes in lipid metabolism, membrane biophysics, intracellular trafficking, and organelle organization. These membrane-centered defenses restrict viral entry, alter endomembrane permissiveness, interfere with virion release, and disrupt the formation and function of virus-induced replication organelles. We further discuss how positive-strand RNA viruses counteract these pressures by reprogramming lipid metabolism and actively remodeling intracellular membranes to preserve replication-competent niches. Together, these observations support a unifying framework in which viruses and host defenses compete for control over membrane identity, organization, and accessibility. This membrane-centered perspective connects innate immune signaling, membrane homeostasis, and viral replication, and highlights membrane-associated processes as promising targets for broad-spectrum antiviral strategies.</p>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":" ","pages":"101058"},"PeriodicalIF":6.3,"publicationDate":"2026-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149317625","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":"Repurposing Ionophores to Tackle Antimicrobial Resistance with a Focus on PBT2.","authors":"Huiting Chen, Michael P Jennings, Freda E-C Jen","doi":"10.1016/j.bj.2026.101057","DOIUrl":"https://doi.org/10.1016/j.bj.2026.101057","url":null,"abstract":"<p><p>Antimicrobial resistance (AMR) remains a growing global health challenge. While resistant bacterial strains continue to emerge and spread, the development of new antibiotics has remained slow. This gap has increased interest in drug repurposing as a promising strategy to combat multidrug-resistant (MDR) pathogens. Ionophores are a structurally diverse group of natural and synthetic compounds that transport ions across biological membranes. Many ionophores were originally developed and widely used for the prevention and treatment of coccidiosis, a common protozoan parasitic intestinal disease in poultry and livestock. Recent studies suggest that some ionophores inhibit bacterial growth directly or enhance the activity of existing antibiotics by perturbing bacterial metal homeostasis, inducing oxidative stress, disturbing membrane function and disrupting biofilms. Among these compounds, PBT2, an 8-hydroxyquinoline derivative with zinc/copper ionophore activity, is an important example. PBT2 acts principally as an antibiotic adjuvant, restoring the activity of conventional antibiotics against several MDR pathogens when combined with zinc. PBT2 also demonstrates narrow-spectrum bactericidal activity as a monotherapy against selected Gram-negative bacteria, including Neisseria gonorrhoeae, Neisseria meningitidis and Helicobacter pylori. PBT2 has prior human exposure from Phase II trials in neurodegenerative diseases, but its antibacterial pharmacokinetics and pharmacodynamics remain undefined. This review summarises the discovery, classification and repurposing of ionophores, and examines the antibacterial activities of PBT2 and its proposed mechanisms of action. Finally, we discuss the translational barriers to the clinical use of ionophores, including bacterial selectivity, resistance risk, toxicity and safety.</p>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":" ","pages":"101057"},"PeriodicalIF":6.3,"publicationDate":"2026-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149242790","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":"Intermittent Parathyroid Hormone Mitigates Cyclophosphamide-Impaired Angiogenic-Osteogenic Patterns during Socket Healing.","authors":"Zhiwei Wang, Naoki Tsuji, Kazuto Hoshi, Atsuhiko Hikita","doi":"10.1016/j.bj.2026.101056","DOIUrl":"https://doi.org/10.1016/j.bj.2026.101056","url":null,"abstract":"<p><strong>Background: </strong>Medication-related osteonecrosis of the jaw (MRONJ) is characterized by impaired post-extraction bone healing, and altered angiogenesis has been implicated in its multifactorial pathogenesis. However, how vascular patterning evolves during impaired extraction socket healing remains insufficiently described. In this study, cyclophosphamide (Cy) and intermittent PTH (iPTH) were applied as opposing modulators of angiogenesis and osteogenesis to investigate how altered angiogenic patterning relates to bone regeneration during Cy-induced delayed extraction socket healing.</p><p><strong>Materials and methods: </strong>Following Cy administration, six- to eight-week-old female C57BL/6J mice underwent maxillary first molar extraction, and iPTH was administered daily to designated groups. Samples were collected on day 3 and day 7. Newly formed vessels and bone in the extraction socket were assessed using micro-CT, histology, immunofluorescence staining, and qualitative lightsheet imaging. In vitro experiments using HUEhT-2 and MC3T3-E1 cells assessed how 4-hydroperoxy cyclophosphamide (4-HC) and iPTH influenced cell viability, migration, and functional behavior.</p><p><strong>Results: </strong>Cy treatment was associated with impaired early vascular growth and altered vascular morphology, together with reduced bone formation. Compared with Cy alone, iPTH was associated with greater vessel area and length on day 3 and more vascular branch points on days 3 and 7, but did not significantly improve all vascular or bone outcomes. In vitro, iPTH improved the viability and migration of 4-HC-treated HUEhT-2 endothelial cells, whereas clear recovery was not observed in MC3T3-E1 preosteoblast-like cells.</p><p><strong>Conclusions: </strong>Cy-induced delayed extraction socket healing was accompanied by vascular impairment, suggesting that altered angiogenesis may be one of several contributors to delayed healing. iPTH improved some vascular features but did not uniformly restore vascular or bone outcomes, indicating that angiogenic-osteogenic coupling in impaired extraction socket healing needs further study.</p>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":" ","pages":"101056"},"PeriodicalIF":6.3,"publicationDate":"2026-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149236744","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":"GABAergic Interneurons in the Insular Cortex Alleviate Acute Stress-Induced Gastric Injury by Suppressing the IC-NTS Glutamatergic Pathway.","authors":"Yuwei Wang, Fanghao Dong, Min Li, Zepeng Wang, Na Li, Xiaoli Ma, Haiji Sun","doi":"10.1016/j.bj.2026.101055","DOIUrl":"https://doi.org/10.1016/j.bj.2026.101055","url":null,"abstract":"<p><p>Acute stress induces gastric mucosal injury, but the central mechanisms remain unclear. We investigated whether GABAergic interneurons, particularly somatostatin (SST) neurons, in the insular cortex (IC) are involved using restraint water-immersion stress (RWIS) in mice. RWIS upregulated GAD65 and SST but downregulated parvalbumin (PV) in the IC. Chemogenetic inhibition of IC GABAergic or SST neurons exacerbated gastric mucosal injury and reduced gastric tight junction proteins (Occludin, Claudins) and PCNA, whereas activation of SST neurons attenuated injury and increased these proteins. Inhibiting IC SST neurons projecting specifically to the nucleus tractus solitarius (NTS) did not affect injury. However, simultaneous inhibition of both SST and glutamatergic neurons in the IC significantly reduced injury and increased Occludin, Claudins, and PCNA levels compared to SST inhibition alone. Thus, IC SST neurons protect against RWIS-induced gastric injury by indirectly suppressing glutamatergic activity in the IC-NTS pathway.</p>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":" ","pages":"101055"},"PeriodicalIF":6.3,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149214873","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":"Context-Dependent Associations of HO-1 Modulation with Ferroptosis-Associated Injury and Vascular Cell Functions In Vitro.","authors":"Patrick Yan-Tyng Liu, Kang-Shuo Chang, Wei-Yin Lin, Horng-Heng Juang","doi":"10.1016/j.bj.2026.101054","DOIUrl":"https://doi.org/10.1016/j.bj.2026.101054","url":null,"abstract":"<p><strong>Background: </strong>Heme oxygenase-1 (HO-1) participates in vascular redox regulation, but its context-dependent relationships with ferroptosis-associated endothelial injury and vascular-cell functions remain incompletely defined.</p><p><strong>Material and methods: </strong>Human umbilical vein endothelial cells (HUVECs), human aortic endothelial cells (HAECs), and human aortic smooth muscle cells (HASMCs) were examined using FAC/RSL3 treatment, hydrogen peroxide, iron chelator Dp44MT, HO-1 inducer cobalt protoporphyrin (CoPP), HO-1 inhibitor Zn(II) protoporphyrin IX (ZnPP), HO-1 knockdown, and HO-1 overexpression. Outcomes included viability, lipid peroxidation, Annexin V/PI staining, total assay-detectable cellular iron, mitochondrial Fe²⁺-associated fluorescence, ROS, protein abundance, proliferation, tube-network formation, and collagen-gel contraction.</p><p><strong>Results: </strong>FAC/RSL3 treatment produced cell injury accompanied by increased lipid peroxidation and sensitivity to liproxstatin-1. Dp44mT reduced FAC-associated total cellular iron and mitochondrial Fe²⁺ signals and attenuated several injury-associated readouts. Pharmacological and genetic modulation of HO-1 was associated with changes in FAC/RSL3/Dp44mT responses, ROS levels, proliferation, and tube network formation. In HASMCs, CoPP treatment was associated with reduced ROS levels and collagen-gel contraction, as well as altered protein abundance of GDF15 and WISP1.</p><p><strong>Conclusions: </strong>The findings identify context-dependent associations between HO-1 modulation and vascular-cell responses in vitro. This study highlights HO-1 as a versatile regulator of vascular cell function, providing a critical molecular framework for developing novel therapeutic strategies to treat atherosclerosis and related cardiovascular diseases.</p>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":" ","pages":"101054"},"PeriodicalIF":6.3,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149147570","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":"Harnessing Acoustic Energy Against Orthopedic Biofilms: Ultrasound-Based Therapeutic Strategies for Implant-Associated and Bone Infections.","authors":"Wael Farchoukh, Bshara Sleem, Ahmad Hammad, Jeffrey Yammine, Said Saghieh, Rida Kassim","doi":"10.1016/j.bj.2026.101045","DOIUrl":"https://doi.org/10.1016/j.bj.2026.101045","url":null,"abstract":"<p><p>Orthopedic implant-associated and bone infections remain difficult to eradicate because microorganisms can establish biofilms on prosthetic surfaces, devitalized bone, and synovial aggregates. These communities impede antimicrobial penetration and host clearance, while metabolically altered and persister-like states further contribute to treatment failure and recurrence. Ultrasound-based technologies are being investigated as adjunctive strategies because acoustic energy can provide mechanical biofilm disruption, trigger local drug release, activate sonosensitizers, enhance catalytic reactions, and, in selected systems, modulate the infected tissue microenvironment. This narrative review critically examines the mechanistic basis and translational evidence for ultrasound-assisted antimicrobial delivery, phase-transition systems, sonodynamic therapy (SDT), ultrasound-enhanced nanozyme catalysis, piezocatalytic strategies, and multifunctional hydrogel platforms in orthopedic infection. Particular attention is given to the maturity and clinical relevance of the infection models, the contribution of non-ultrasound co-therapies, ultrasound dose reporting, and the distinction between direct regenerative effects and secondary recovery after bacterial clearance. Current evidence remains predominantly preclinical and heterogeneous, and clinical translation will require standardized acoustic dosimetry, chronic and polymicrobial infection models, tissue-specific safety assessment, and integration with established surgical and antimicrobial pathways.</p>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":" ","pages":"101045"},"PeriodicalIF":6.3,"publicationDate":"2026-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149103550","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":"Clinical Landscape of Microbiome Modulators in Gynecological Tumor Treatment: From Pre-Clinical to Clinical Trials.","authors":"Jiaxin Zhang, Xiaohui Jiang, Zilin Lin, Hong Li, Sunlu Jiang","doi":"10.1016/j.bj.2026.101043","DOIUrl":"https://doi.org/10.1016/j.bj.2026.101043","url":null,"abstract":"<p><p>Intestinal microbiota dysbiosis is linked to gynecological tumors (endometrial, ovarian, cervical cancers), and microbiome modulators show therapeutic potential by regulating gut microbiota. This Perspective analyzes the field from pre-clinical to clinical stages. Pre-clinically, a Web of Science bibliometric analysis (2010-2025, 114 articles, 86 reviews) revealed focus on \"epithelial ovarian cancer,\" \"estrogen,\" and \"mechanism,\" with key studies by Baker et al. (2017, gut microbiota-estrogen-endometrial cancer link) and Kopustinskiene et al. (2020, flavonoids' anti-tumor effect via gut flora). Clinically, 4 INFORMA-database trials (2 closed, 1 completed, 1 planning) targeted ovarian/endometrial cancer (no cervical cancer trials), using live microorganisms/faecal modulators mainly for immuno-oncology therapy; bacteriophages (e.g., M13) also emerged as potential modulators. Challenges include unclear optimal combination therapies, lack of cervical cancer trials, and limited modulator types. This analysis offers a field overview and future research directions. The intestinal microbiota constitutes a complex ecological community that influences the normal physiological and pathological processes of distal organs through its metabolic activities. Previous research has demonstrated that dysbiosis of the intestinal microbiota can contribute to the development of endometrial cancer, ovarian cancer, and cervical cancer ^1-3. Microbiome modulators enhance host health by regulating the intestinal microbiota and hold potential as therapeutic agents for gynecological tumors ⁴. Consequently, it is imperative to analyze the landscape of clinical trials investigating the efficacy of microbiome modulators in the treatment of gynecological tumors.</p>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":" ","pages":"101043"},"PeriodicalIF":6.3,"publicationDate":"2026-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149103610","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":"Backs under pressure: measuring and estimating lumbar spinal loads","authors":"Aila Akosua Kattner (Scientific Communicator)","doi":"10.1016/j.bj.2026.101042","DOIUrl":"10.1016/j.bj.2026.101042","url":null,"abstract":"<div><div>This issue of the <em>Biomedical Journal</em> examines lumbar spinal loading and current approaches to its assessment using invasive measurements, biomechanical modeling, imaging, wearable technologies, and AI-assisted methods. Other contributions address coumarin derivatives as modulators of autophagy and PI3K/mTOR signaling in cancer and apply multi-omics approaches to uric acid metabolism and cardiometabolic disease. Further studies investigate molecular mechanisms linking mechanical irritation to oral squamous cell carcinoma progression, predictors of HBsAg seroclearance after antiviral treatment withdrawal, and age-dependent effects of exercise and losartan. Additional contributions explore PD-L1 signaling in allergic asthma, the antiviral activity of BPR2-D2 against chikungunya virus replication, and differences in objective tear function between patients with and without mental disorders.</div></div>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":"49 5","pages":"Article 101042"},"PeriodicalIF":6.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149057696","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}

{"title":"Zfp469 Deletion Attenuates Liver Fibrosis by Suppressing Extracellular Matrix Production in Hepatic Stellate Cells.","authors":"Nantawat Satthawiwat, Archittapon Nokkeaw, Bootsakorn Boonkaew, Chinnatam Phetkong, Denita Charoenthanakitkul, Nuchanart Suntornnont, Ratchanon Wiphuosana, Thammachanok Boonto, Wirawit Srivongtrakul, Xinyu Wu, Chaiyaboot Ariyachet","doi":"10.1016/j.bj.2026.101044","DOIUrl":"https://doi.org/10.1016/j.bj.2026.101044","url":null,"abstract":"<p><strong>Background: </strong>Liver fibrosis is driven by excessive extracellular matrix (ECM) deposition following chronic injury. Mutations in the human zinc finger protein 469 (ZNF469) cause Brittle Cornea Syndrome, a systemic connective tissue disorder, yet its functional role in hepatic fibrogenesis remains unexplored in vivo. This study investigated the impact of the murine ortholog, Zfp469, on liver fibrosis using CRISPR-generated knockout (KO) models and integrated transcriptomic and cellular analyses.</p><p><strong>Materials and methods: </strong>Zfp469-KO and wild-type mice were subjected to chronic carbon tetrachloride (CCl₄) administration or a choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD). Fibrosis was quantified via Masson's trichrome and Sirius Red staining. To assess cell-intrinsic effects, primary hepatic stellate cells (HSCs) were isolated for in vitro activation assays. Bulk and single-cell RNA sequencing datasets across toxic, metabolic, and cholestatic models were analyzed via pseudotime trajectory and single-cell co-expression network frameworks to map Zfp469 dynamics and network topology.</p><p><strong>Results: </strong>Zfp469 deficiency significantly attenuated collagen accumulation and mitigated the progression of liver injury in both toxin- and diet-induced models. Importantly, the loss of Zfp469 did not alter baseline liver morphology or homeostasis. At the cellular level, Zfp469-KO HSCs exhibited a blunted activation response with reduced expression of key myofibroblast markers (Col1a1, Col1a2, and Acta2) in vitro. Multi-model transcriptomic profiling demonstrated that Zfp469 is specifically enriched in activated HSCs, occupies key network modules, and exhibits etiology-dependent activation kinetics while maintaining a conserved pro-fibrotic gene signature.</p><p><strong>Conclusions: </strong>This study provides the first in vivo evidence that Zfp469 is a critical, cell-autonomous regulator of hepatic ECM production. By demonstrating that Zfp469 is required for pathological fibrogenesis but dispensable for normal liver function, our findings identify the Zfp469-ECM axis as a promising therapeutic target for chronic liver diseases.</p>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":" ","pages":"101044"},"PeriodicalIF":6.3,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149073213","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":"The Mononuclear Phagocyte System: A Dispersed Organ; Introduction and Comments.","authors":"Hsi-Hsien Lin, Kirtana Sivasubramanian, Annabell Roberti, Siamon Gordon","doi":"10.1016/j.bj.2026.101041","DOIUrl":"https://doi.org/10.1016/j.bj.2026.101041","url":null,"abstract":"<p><p>Mononuclear phagocytes are widely distributed throughout the body and interact with other cellular systems to preserve homeostasis and health. Recent studies have revealed the remarkable plasticity and adaptability of their cellular recognition and trophic responses beyond phagocytosis and immunity. We invited several early-career investigators to review the nature and interactions of selected Mononuclear Phagocyte populations within established organ systems, apart from lympho-haematopoietic tissues. This special issue indicates that the Mononuclear Phagocyte System (MPS) can be considered on a par with Neuro-Endocrine and other physiologic organ systems in the mouse and human. As a guide to the context of individual reviews, we provide a concise overview of the field and suggestions for further reading and research.</p>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":" ","pages":"101041"},"PeriodicalIF":6.3,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149015557","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}