Military Medical Research最新文献

{"title":"The concept of neurogenic organ dysfunction is not new and should encompass all aspects of the underlying pathophysiological mechanisms.","authors":"Josef Finsterer","doi":"10.1016/j.mmr.2026.100052","DOIUrl":"10.1016/j.mmr.2026.100052","url":null,"abstract":"","PeriodicalId":18581,"journal":{"name":"Military Medical Research","volume":"13 1","pages":"100052"},"PeriodicalIF":29.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13321067/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148368873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuro-skeletal units and Smart Analgesia: reprogramming sensory neurons for fracture repair.","authors":"Long Bai, Jia-Can Su","doi":"10.1016/j.mmr.2026.100044","DOIUrl":"10.1016/j.mmr.2026.100044","url":null,"abstract":"","PeriodicalId":18581,"journal":{"name":"Military Medical Research","volume":"13 1","pages":"100044"},"PeriodicalIF":29.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13264228/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148252133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Accelerating global efforts to prevent women's cancers.","authors":"Leeya F Pinder","doi":"10.1016/j.mmr.2026.100062","DOIUrl":"https://doi.org/10.1016/j.mmr.2026.100062","url":null,"abstract":"","PeriodicalId":18581,"journal":{"name":"Military Medical Research","volume":"13 1","pages":"100062"},"PeriodicalIF":29.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13487707/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148795315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nanobodies in biomedicine: from molecular characteristics to fabrication and clinical translation.","authors":"Cheng-Kun Cao, Xin-Yi Xu, Fei Liang, Min Yao, Yuan-Yuan Chen, Xiao-Kun Li, Zhi-Jian Su","doi":"10.1016/j.mmr.2026.100009","DOIUrl":"10.1016/j.mmr.2026.100009","url":null,"abstract":"<p><p>Nanobodies (Nbs), the antigen-binding single-domain fragments derived from camelid heavy-chain antibodies (Abs), have rapidly become a focus of biomedical research due to their compact size, high stability, strong antigen affinity, and ease of molecular engineering. This review systematically outlines their structural and functional features, current strategies for acquisition, screening, optimization, and large-scale production, and comprehensively discusses their wide-ranging applications in therapeutics, diagnostics, and basic research. Specifically, Nbs have shown outstanding efficacy in tumor, toxin, infectious, and cardiovascular disease treatments, while serving as versatile tools for molecular imaging, biosensing, protein purification, structural analysis, and intracellular regulation. The challenges of immunogenicity, off-target effects, and industrial-scale manufacturing are also critically examined. Furthermore, the integration of artificial intelligence in structure prediction, de novo design, and immunogenicity assessment has opened powerful new avenues for rational Nb engineering. Combined with emerging technologies such as gene therapy, nanomaterial delivery, and multispecific architectures, these advances promise to accelerate clinical translation. Overall, Nb technology is poised to become a cornerstone of next-generation precision medicine and biotechnology, offering innovative solutions for disease diagnosis, targeted therapy, and molecular discovery.</p>","PeriodicalId":18581,"journal":{"name":"Military Medical Research","volume":"13 1","pages":"100009"},"PeriodicalIF":29.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13127154/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147817503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Blockade of EP3 attenuates cardiac fibrosis by suppressing TGF-β1-Smad2/3 signaling through the Smurf2-mediated Smad7 ubiquitination.","authors":"Lan Ye, Hu Xu, Hui Tang, Qing-Wei Li, Xiu-Hui Mao, Er-Jiao Qiang, Jia-Yao Zhang, Bo Liang, Li-Hong Chen, You-Fei Guan, Xiao-Yan Zhang","doi":"10.1016/j.mmr.2026.100071","DOIUrl":"10.1016/j.mmr.2026.100071","url":null,"abstract":"<p><strong>Background: </strong>Sustained β-adrenergic activation induces cardiac fibrosis, which is characterized by excessive deposition of extracellular matrix (ECM) secreted by activated cardiac fibroblasts (CFs). Prostaglandin E₂ (PGE₂) is a dominant cyclooxygenase metabolite of arachidonic acid and exerts important biological actions by activating four G-protein-coupled receptors, including E-type prostanoid receptors 1-4 (EP1-EP4). The present study aimed to investigate the role of the EP3 receptor in isoproterenol (ISO)-induced cardiac fibrosis.</p><p><strong>Methods: </strong>To elucidate the role of EP3 in cardiac fibrosis, the global <i>EP3</i> gene knockout mice (EP3^-/-) and the LoxP-Cre system-based CF-specific <i>EP3</i> gene knockout mice (EP3^cKO) or cardiomyocyte (CM)-specific <i>EP3</i> gene knockout mice (EP3^mKO) were subcutaneously injected with ISO [5 mg/(kg·d)] for 7 d to establish a cardiac fibrosis model. In parallel, the EP3 agonist sulprostone and the EP3 antagonists DG041 and L798106 were used to elucidate the underlying mechanisms. Finally, the therapeutic potential of the EP3 antagonist DG041 was evaluated in the context of cardiac fibrosis.</p><p><strong>Results: </strong>Echocardiography assay showed that both EP3^-/- and EP3^cKO mice exhibited a significant improvement in cardiac diastolic function. Histological staining revealed that EP3^-/- and EP3^cKO, but not EP3^mKO, exhibited a significant attenuation of ISO-induced CF activation and ECM accumulation. Further investigation uncovered that EP3 was highly expressed in the CFs rather than CMs. Inhibition of EP3 in the CFs suppressed transforming growth factor-β1 (TGF-β1)-triggered phosphorylation of small mother against decapentaplegic (Smad)2/3 and the production of ECM proteins. Mechanistically, the blockade of EP3 in the CFs activated the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway, which promoted the degradation of Smad ubiquitination regulatory factor 2 (Smurf2) and subsequently suppressed the ubiquitination of Smad7, an inhibitory Smad, leading to an increase in the protein level of Smad7. Furthermore, the administration of an EP3 antagonist, DG041, markedly improved ISO-induced cardiac diastolic dysfunction and fibrosis.</p><p><strong>Conclusions: </strong>This study demonstrates that CF-EP3 contributes to β-adrenergic activation-induced cardiac fibrosis and target of EP3 represents a potential therapeutic strategy for the treatment of cardiac fibrosis.</p>","PeriodicalId":18581,"journal":{"name":"Military Medical Research","volume":"13 1","pages":"100071"},"PeriodicalIF":29.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13676097/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149216489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endothelial barrier and sepsis: mechanisms and potential therapeutic strategies.","authors":"Yan-Hong Jiang, Xing-Juan Li, De-Cao Ma, Yong-Lin Chen, Yi-Yu Shi, Yang Lu, Ren-Fang Mao","doi":"10.1016/j.mmr.2026.100013","DOIUrl":"10.1016/j.mmr.2026.100013","url":null,"abstract":"<p><p>Sepsis is a life-threatening condition characterized by an exaggerated and uncontrolled immune response, leading to widespread inflammation throughout the body. This immune response can compromise the integrity of the endothelial barrier, resulting in increased vascular permeability. The degree of vascular permeability in septic shock patients correlates with disease severity and significantly influences the outcomes of resuscitation and prognosis. This review systematically examines the structural regulation of the endothelial barrier and the dynamic mechanisms of its injury in subgroups of sepsis. In response to these mechanisms, emerging therapeutic strategies focus on glycocalyx protection, signal pathway modulation, cytoskeleton stability, and immune regulation, aiming to restore endothelial barrier function through multi-target synergism. In the future, combining analysis of endothelial barrier function and the dynamic regulation mechanism provides a new perspective for the precise treatment of sepsis.</p>","PeriodicalId":18581,"journal":{"name":"Military Medical Research","volume":"13 1","pages":"100013"},"PeriodicalIF":29.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13127147/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147817376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic potential of HDAC6 inhibitor Tubastatin A in health and diseases: current perspective and future directions.","authors":"Sonu Rajput, Sumeet Kumar Singh, Poonam Yadav, Amit Khurana, Ralf Weiskirchen, Umashanker Navik","doi":"10.1016/j.mmr.2026.100024","DOIUrl":"10.1016/j.mmr.2026.100024","url":null,"abstract":"<p><p>Histone deacetylase 6 (HDAC6) is a unique, predominantly cytoplasmic enzyme that regulates a broad spectrum of cellular and physiological processes, including cell proliferation, migration, intracellular transport, and differentiation. Its distinct structural configuration, comprising two catalytic deacetylase domains and a zinc finger ubiquitin-binding domain (ZnF-BUZ), enables HDAC6 to deacetylate a variety of non-histone substrates, such as α-tubulin, heat shock protein 90 (Hsp90), cortactin, and peroxiredoxin (Prdx). Furthermore, HDAC6 plays a key role in cellular stress responses and cell survival by facilitating the clearance of misfolded proteins, inducing autophagy, and modulating the unfolded protein response. Despite its cytoprotective roles, HDAC6 has emerged as a therapeutic target due to its involvement in multiple pathological pathways and age-related disorders. Tubastatin A (Tub A), a novel and highly selective HDAC6 inhibitor, demonstrates strong therapeutic potential against neurodegenerative, cardiovascular, autoimmune, metabolic, cancer, and other diseases. Tub A enhances the acetylation of both histone and non-histone proteins, thereby modulating gene expression and diverse cellular processes. It shows pharmacological effects, including anti-inflammatory, neuroprotective, anti-diabetic, anti-obesity, anti-oxidant, and other activities. Moreover, preclinical evidence suggests that Tub A effectively regulates multiple pathological pathways by inhibiting HDAC6, which contributes to ameliorating age-related disorders. Therefore, Tub A represents a promising epigenetic modulator with broad therapeutic relevance. Hence, further comprehensive and large-scale investigations are warranted to elucidate its clinical potential and its roles in disease management, as no clinical data related to Tub A activity are available. This review highlights the therapeutic potential of the selective HDAC6 inhibitor Tub A across various pathological conditions, discusses current preclinical findings, and outlines key challenges and future directions for clinical translation.</p>","PeriodicalId":18581,"journal":{"name":"Military Medical Research","volume":"13 1","pages":"100024"},"PeriodicalIF":29.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13127153/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147817468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ZBP1 activated by mitochondrial damage binds to STAT3 to suppress Legumain production and exacerbate macrophage inflammation in <i>Klebsiella pneumoniae</i>-induced sepsis.","authors":"Li-Ting Deng, Huan Yang, Xu-Fei Zhang, Ze-Xing Lin, Ni Kuang, Hai-Yang Jiang, Pei-Zhao Liu, Yang-Guang Li, Xuan-Heng Li, Wei-Zhen Li, Chu-Jun Ni, Ming-Jie Qiu, Yue Chao, Yu-Fei Pan, Yi-Yu Yang, Ye-Ting Zhu, Yun Zhao, Jian-An Ren, Xiu-Wen Wu","doi":"10.1016/j.mmr.2026.100059","DOIUrl":"10.1016/j.mmr.2026.100059","url":null,"abstract":"<p><strong>Background: </strong>Severe bacterial sepsis caused by <i>Klebsiella pneumoniae</i> (<i>KP</i>) is characterized by dysregulated inflammation, multiorgan injury, and high mortality, yet the key molecular drivers of this process remain incompletely understood. This study aimed to elucidate how the Z-DNA binding protein 1 (ZBP1) regulates inflammatory injury during <i>KP</i>-induced sepsis and to identify potential therapeutic targets with translational relevance.</p><p><strong>Methods: </strong>To investigate the role of macrophage ZBP1 in sepsis, we combined transcriptomic datasets from human sepsis cohorts and murine sepsis and <i>KP</i>-infection models with single-cell RNA sequencing of infected tissues. We further established both global and myeloid-specific <i>Zbp1</i> knockout (<i>Zbp1</i> ^<i>fl/fl</i> <i>Lyz2-Cre</i> ^<i>+/-</i> ) mice, as well as myeloid-specific <i>Lgmn</i> (encoded Legumain) knockout (<i>Lgmn</i> ^<i>fl/fl</i> <i>Lyz2-Cre</i> ^<i>+/-</i> , <i>Lgmn</i> ^<i>CKO</i> ) mice, to delineate the macrophage-dependent mechanisms of immune regulation. In addition, macrophage-targeted adeno-associated virus 9 (AAV9) vectors driven by the <i>F4/80</i> promoter were used to overexpress <i>Lgmn in vivo</i>. Flow cytometry, immunofluorescence, and survival analyses were performed to evaluate systemic inflammation, organ injury, and sepsis severity. The effect of recombinant LGMN supplementation on macrophage activation and barrier restoration was also assessed.</p><p><strong>Results: </strong>ZBP1 activation was driven by both type I interferon (IFN-I) signaling and mitochondrial damage. Mechanistically, ZBP1 directly interacted with signal transducer and activator of transcription 3 (STAT3), suppressed its phosphorylation and nuclear translocation, and consequently inhibited transcription of <i>Lgmn</i>, a gene associated with anti-inflammatory macrophage polarization and tissue repair. Genetic and myeloid-specific deletion of <i>Zbp1</i> resulted in reduced proinflammatory cytokine production and improved survival in both <i>KP-</i> and cecal ligation and puncture (CLP)-induced sepsis models. In contrast, <i>Lgmn</i> ^<i>CKO</i> aggravated systemic inflammation, organ injury, and barrier dysfunction, whereas macrophage-targeted AAV9-mediated <i>Lgmn</i> overexpression or recombinant LGMN supplementation alleviated macrophage inflammation, restored epithelial function, and improved survival.</p><p><strong>Conclusion: </strong>These findings reveal a previously unrecognized ZBP1-STAT3-LGMN signaling axis that contributes to immune and inflammatory dysregulation in <i>KP</i>-induced sepsis and suggest that targeting ZBP1 or restoring LGMN activity may represent a promising therapeutic strategy for severe bacterial infections.</p>","PeriodicalId":18581,"journal":{"name":"Military Medical Research","volume":"13 1","pages":"100059"},"PeriodicalIF":29.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13452355/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148697781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting intratumoral bacteria reverses MHC-I suppression and enhances nano-based chemoimmunotherapy in colorectal cancer.","authors":"Jing Feng, Yan-Hong Liu, Li-Ming Gong, Wen-Xuan Zhang, Chen-Fei Liu, Cong-Cong Xiao, Li-Qing Chen, Ming-Ji Jin, You-Yan Guan, Zhong-Gao Gao, Wei Huang","doi":"10.1016/j.mmr.2026.100036","DOIUrl":"10.1016/j.mmr.2026.100036","url":null,"abstract":"<p><strong>Background: </strong>Emerging evidence indicates that diverse bacteria colonize tumors and facilitate oncogenesis through multifaceted mechanisms, predominantly through immunosuppression of the tumor microenvironment (TME). <i>Fusobacterium nucleatum</i> (<i>F.n</i>) exemplifies this phenomenon in colorectal cancer (CRC), where it mediates immune evasion via tumor cell autophagy and upregulation of programmed death-ligand 1 (PD-L1). Effective strategies for combining precise elimination of intratumoral <i>F.n</i> with chemotherapy remain lacking.</p><p><strong>Methods: </strong>A targeted multimodal nano-based chemoimmunotherapy was engineered by co-loading hyaluronic acid (HA)-coated silver nanoparticles (Ag NPs) and paclitaxel (PTX) into tumor-targeting cationic liposomes (Cls). The combination was mechanistically evaluated for <i>F.n</i> eradication capacity, antitumor effects, and remodeling of the tumor immune microenvironment. Antitumor efficacy and safety were also evaluated <i>in vivo</i> using a tumor-bearing mouse model.</p><p><strong>Results: </strong>Intratumoral <i>F.n</i> subverted antitumor immunity through a dual mechanism, coupling major histocompatibility complex class I (MHC-I) degradation with PD-L1 upregulation. HA@Ag NPs/PTX Cls exerted synergistic antitumor effects through multimodal mechanisms. HA@Ag NPs/PTX Cls eliminated intratumoral bacteria, restoring microbial homeostasis, enhancing MHC-I antigen presentation, increasing production of tumor necrosis factor (TNF) and interferon (IFN), and downregulating PD-L1 to promote tumor immunorecognition. Combined with PTX-induced apoptosis, the nanotherapy inhibited both primary and metastatic tumors. Notably, bacterial clearance-triggered immune activation established long-term immunological memory, providing durable protection against tumor recurrence. These results highlighted the dual benefit of liposomes in addressing microbial dysbiosis and immune evasion in CRC.</p><p><strong>Conclusion: </strong>This innovative liposomal strategy disrupts the immunosuppressive TME and synergizes with a small-molecule chemotherapeutic agent to induce tumor cell apoptosis, representing a novel approach to potentiate cancer immunotherapy.</p>","PeriodicalId":18581,"journal":{"name":"Military Medical Research","volume":"13 1","pages":"100036"},"PeriodicalIF":29.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13185994/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147982004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retinal fundus images do not reflect brain volume, provided all predisposing factors influencing brain size are taken into account.","authors":"Josef Finsterer","doi":"10.1016/j.mmr.2026.100034","DOIUrl":"10.1016/j.mmr.2026.100034","url":null,"abstract":"","PeriodicalId":18581,"journal":{"name":"Military Medical Research","volume":"13 1","pages":"100034"},"PeriodicalIF":29.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13157085/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147868845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}