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Gut microbiota and hypertension: role of exercise training. 肠道微生物群与高血压:运动训练的作用。
IF 3.5 4区 医学
Clinical and Experimental Hypertension Pub Date : 2026-12-31 Epub Date: 2025-12-27 DOI: 10.1080/10641963.2025.2608905
Meng Zhao, Qi Liu, Na-Jie Shi, Ying Li, Hong-Bao Li
{"title":"Gut microbiota and hypertension: role of exercise training.","authors":"Meng Zhao, Qi Liu, Na-Jie Shi, Ying Li, Hong-Bao Li","doi":"10.1080/10641963.2025.2608905","DOIUrl":"https://doi.org/10.1080/10641963.2025.2608905","url":null,"abstract":"<p><p>Regular exercise training can significantly improve the gut environment and influence the metabolic activity of the gut microbiota. These changes promote the production of beneficial metabolites, which may modulate blood pressure regulation through multiple mechanisms. The beneficial microbial species including <i>Faecalibacterium prausnitzii</i>, <i>Bifidobacterium</i> spp., <i>Lactobacillus</i> spp., <i>Roseburia</i> spp.,and <i>Bacteroides</i> spp. These beneficial microbes produce various metabolites during metabolism, including short-chain fatty acids, vitamins, lactic acid, bileacids, and gamma-aminobutyric acid. These metabolites are not only essential for maintaining gut health but also positively influence hypertension by modulating the nervous system, immune system, and improving metabolic function. This review aims to elucidate the complex interactions among exercise training, gut microbiota, and hypertension.</p>","PeriodicalId":10333,"journal":{"name":"Clinical and Experimental Hypertension","volume":"48 1","pages":"2608905"},"PeriodicalIF":3.5,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145846328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Long-term management of psoriasis recurrence via modulation of cutaneous microbiome: synergistic topical therapy with blue light and aptamer-functionalized curcumin formulation. 银屑病复发的长期管理通过调节皮肤微生物组:协同局部治疗蓝光和适配体功能化姜黄素制剂。
IF 8.1 2区 医学
Drug Delivery Pub Date : 2026-12-31 Epub Date: 2026-01-03 DOI: 10.1080/10717544.2025.2610532
Nan Jin, Yaling Chen, Huangyu Luo, Yanhong Su, Yumin Weng, Xin Lin, Tingting Zheng, Bingbing Li, Tianhui Liu, Jianmin Chen
{"title":"Long-term management of psoriasis recurrence via modulation of cutaneous microbiome: synergistic topical therapy with blue light and aptamer-functionalized curcumin formulation.","authors":"Nan Jin, Yaling Chen, Huangyu Luo, Yanhong Su, Yumin Weng, Xin Lin, Tingting Zheng, Bingbing Li, Tianhui Liu, Jianmin Chen","doi":"10.1080/10717544.2025.2610532","DOIUrl":"https://doi.org/10.1080/10717544.2025.2610532","url":null,"abstract":"<p><p>The recurrence following the discontinuation of medication is a formidable challenge in managing psoriasis. Changes in the microbiome accompany the onset of psoriasis relapse, highlighting a potential therapeutic modality. To evaluate the superiority of the topical administration of aptamer-functionalized curcumin mesoporous silica (Apt-GA+Cur@μmS) plus blue light (BL) in restoring dysbiosis and intervening in recurrence in a murine model, a psoriasis relapse murine model with double imiquimod induction was established. With a BL-responsive shell, Apt-GA+Cur@μmS released curcumin (Cur) to assist BL to improve the preventative and therapeutic effects in the psoriasis relapse murine model, as evidenced by the psoriasis area and severity index, histology, splenic index, and dorsal IL-17A level. We also observed a negative correlation between splenic nitric oxide (NO) levels and the splenic index, indicating a possible mechanism by which Apt-GA+Cur@μmS&BL may function in the treatment of splenomegaly. Treatment with Apt-GA+Cur@μmS&BL exhibited a higher alpha diversity than the model group, with levels similar to those of healthy mice, indicating that this combination could adjust the composition of the dorsal microbiome to a healthier state. A reduction in the combined relative abundance of <i>Staphylococcus</i>, <i>Streptococcus,</i> and <i>Corynebacterium</i> as well as restoration of dysbiosis was also verified through 16S rDNA gene sequencing <i>in vivo</i>. Collectively, BL and Apt-GA+Cur@μmS cotherapy alleviates psoriasiform lesions in a double imiquimod-induced murine model by inhibiting IL-17A and increasing splenic NO. Additionally, this cotherapy restores the eubiosis of the dorsal lesions. Thus, it is a promising and innovative therapeutic modality for psoriasis inflammation alleviation and recurrence intervention.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"33 1","pages":"2610532"},"PeriodicalIF":8.1,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145892446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Beyond the classroom: a qualitative study of voluntary home visits to older adults as a tool for empathy and professional growth in medical students. 课堂之外:对老年人自愿家访作为医学生移情和专业成长工具的定性研究。
IF 3.8 2区 医学
Medical Education Online Pub Date : 2026-12-31 Epub Date: 2025-12-22 DOI: 10.1080/10872981.2025.2605378
Adi Finkelstein, Naama Constantini, Netanel Gelkop, Tamar Guttman, Anya Krichevsky, Naama Mittelman, Gavriel Parker Sahala, Nir Weigert, Mici Phillips, Ohad Avny, Tali Sahar
{"title":"Beyond the classroom: a qualitative study of voluntary home visits to older adults as a tool for empathy and professional growth in medical students.","authors":"Adi Finkelstein, Naama Constantini, Netanel Gelkop, Tamar Guttman, Anya Krichevsky, Naama Mittelman, Gavriel Parker Sahala, Nir Weigert, Mici Phillips, Ohad Avny, Tali Sahar","doi":"10.1080/10872981.2025.2605378","DOIUrl":"https://doi.org/10.1080/10872981.2025.2605378","url":null,"abstract":"<p><p>Global populations are rapidly aging, posing significant challenges. Yet, ageism among clinicians and medical students persists, undermining empathy and care quality. Traditional short-term educational efforts have limited effect; sustained, relationship-based programs hold promise but remain understudied. To address this, we implemented a year-long service-learning project, where first-year medical students visit elderly individuals at their homes to engage in light physical activities and discuss life challenges. This qualitative study examines the project's impact on first, second, and third-year medical students.From August to October 2020, we recruited, via convenience sampling, first-year medical students of three consecutive cohorts (<i>n</i> = 313) that completed ten home visits with older adults; of these sixty (19%) students participated in focus groups/interviews and 128 (41%) submitted reflective assignments. Data was manually analyzed using Braun and Clarke's six-phase reflexive thematic approach until saturation. We adhered to the COREQ (Consolidated Criteria for Reporting Qualitative Research) checklist.Three major themes and seven sub-themes emerged. First, building trusting patient-physician relationships, characterized by empathy, trust, and effective communication, alongside a balance between physician responsibility and patient autonomy. Second, embracing uncertainty and holistic care, which involved navigating medical ambiguity and integrating psychosocial dimensions into clinical reasoning. Third, reflecting on vulnerability, aging, and mortality, encompassing the emotional impact of disability and decline; reframing aging positively; and processing experiences of death and loss. Participants described profound shifts in their perspectives on aging, care relationships, and their professional identities; changes that persisted throughout their pre-clinical training. To conclude, early and sustained engagement with older adults in their home environment through a structured service-learning project enhanced medical students' professional development, empathy, and attitudes toward aging. Incorporating similar programs into medical education curricula may provide substantial pedagogical benefits. Future research should assess long-term impacts on career choices and care quality.</p>","PeriodicalId":47656,"journal":{"name":"Medical Education Online","volume":"31 1","pages":"2605378"},"PeriodicalIF":3.8,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145811666","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A dual diacylglycerol kinase (DGK) alpha/zeta inhibitor augments the activity of human tumor infiltrating lymphocytes in in vivo and ex vivo models. 双二酰基甘油激酶(DGK) α /zeta抑制剂在体内和离体模型中增强了人肿瘤浸润淋巴细胞的活性。
IF 6.5 2区 医学
Oncoimmunology Pub Date : 2026-12-31 Epub Date: 2025-12-29 DOI: 10.1080/2162402X.2025.2608439
Phurin Areesawangkit, Karen Pei-Yi Fong, Emma Niemeyer, Yan Li, Kelly Markowitz, Devora Delman, Ryan Krause, Justine Carl, Pat Feldman, Lisa Troung, Rodrigo Hess, Xiaodi Ren, Cynthia Timmers, Sunkyu Kim, Robert Brody, Sunil Singhal, Jarrod Predina, Evgeniy Eruslanov, Gregory Beatty, Bihui Melidosian, Steven M Albelda
{"title":"A dual diacylglycerol kinase (DGK) alpha/zeta inhibitor augments the activity of human tumor infiltrating lymphocytes in <i>in vivo</i> and <i>ex vivo</i> models.","authors":"Phurin Areesawangkit, Karen Pei-Yi Fong, Emma Niemeyer, Yan Li, Kelly Markowitz, Devora Delman, Ryan Krause, Justine Carl, Pat Feldman, Lisa Troung, Rodrigo Hess, Xiaodi Ren, Cynthia Timmers, Sunkyu Kim, Robert Brody, Sunil Singhal, Jarrod Predina, Evgeniy Eruslanov, Gregory Beatty, Bihui Melidosian, Steven M Albelda","doi":"10.1080/2162402X.2025.2608439","DOIUrl":"10.1080/2162402X.2025.2608439","url":null,"abstract":"<p><p>Endogenous or adoptively transferred tumor-infiltrating lymphocytes (TILs) often lose their functional capacity due to the activation of intrinsic inhibitory pathways, which then limits their ability to control tumor growth. In this study, we examined the effects of blocking a key intracellular inhibitory enzyme, diacylglycerol kinase (DGK) in human T cells, using a novel inhibitor (DGKi) called INCB165451 that blocks both DGKα and DGKζ, the two primary DGK isoenzymes that negatively regulate T cells through the diacylglycerol (DAG) signaling pathway. We first evaluated the effects of the DGKi in enhancing the efficacy of adoptive human T cell transfer in a non-small cell lung cancer (NSCLC) mouse model and found that the DGKi significantly potentiated anti-tumor efficacy through multiple mechanisms, including increased intratumoral T cell infiltration, upregulation of genes associated with inflammatory responses, and reduction of TIL hypofunction, as evidenced by enhanced cytokine production following ex vivo anti-CD3 antibody stimulation. We next studied the effects of the DGKi on human TILs derived from tumor digests or studied <i>in situ</i> in precision-cut tumor slices of both head and neck cancer and NSCLC patient samples. After stimulation of the TILs with anti-CD3 antibodies, we found that the DGKi enhanced gene and protein expression of proinflammatory cytokines and chemokines. Finally, we demonstrated that the DGKi could augment T cell activation in human tumor slices that were stimulated by an anti-EGFR/anti-CD3 bispecific T cell engager (BiTE). These data demonstrate strong activity of the DGKi in human TILs and highlight promising potential avenues for clinical translation.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"15 1","pages":"2608439"},"PeriodicalIF":6.5,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12758329/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145851153","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}
引用次数: 0
Differential expression of mitomiRs in pancreatic islet cells associated with maternal protein restriction. 与母体蛋白限制相关的胰岛细胞mitomir差异表达。
IF 1.7 4区 医学
Islets Pub Date : 2026-12-31 Epub Date: 2026-01-01 DOI: 10.1080/19382014.2025.2610590
Cecile Jacovetti, Romano Regazzi
{"title":"Differential expression of mitomiRs in pancreatic islet cells associated with maternal protein restriction.","authors":"Cecile Jacovetti, Romano Regazzi","doi":"10.1080/19382014.2025.2610590","DOIUrl":"10.1080/19382014.2025.2610590","url":null,"abstract":"<p><strong>Objective: </strong>Mitochondria are central to energy production and cellular homeostasis. Beyond importing diverse RNAs, they also encode hundreds of their own non-coding RNAs, contributing to a complex and dynamic RNA landscape. Early-life nutritional insults, such as fetal and postnatal protein deficiency, can impair mitochondrial function and increase the long-term diabetes risk. However, the mitochondrial non-coding transcriptome of pancreatic islets, particularly its responsiveness to nutritional cues, remains largely unexplored.</p><p><strong>Methods: </strong>We performed RNA sequencing to profile small non-coding RNAs in mitochondrial fractions of islet cells from offspring of rats exposed to low-protein (LP) or control diets during gestation and lactation and employed mRNA-miRNA network analysis to explore the potential regulatory roles of differentially expressed mitomiRs in LP-exposed pups.</p><p><strong>Results: </strong>Protein deficiency during gestation and lactation led to a profound remodeling of the small non-coding RNA landscape in whole islets, with microRNAs and piRNAs showing the most pronounced changes. In mitochondrial fractions, LP exposure resulted in a striking shift in microRNA composition, with 33 mitomiRs detected in control islets versus 23 in LP-exposed rats, and only 5 shared between groups. Notably, ten mitomiRs were selectively depleted from the cytosol and enriched in mitochondria of LP-exposed islets. Amongst these, miR-10a-5p and miR-126a-5p, are predicted to target genes involved in mitochondrial metabolism and structural organization.</p><p><strong>Conclusion: </strong>Early-life protein restriction triggers a highly selective reorganization of the mitomiR landscape in pancreatic islets. The identified mitomiRs may serve as regulators of mitochondrial function and intracellular signaling, potentially influencing <i>β</i>-cell metabolic coupling and contributing to diabetes susceptibility.</p>","PeriodicalId":14671,"journal":{"name":"Islets","volume":"18 1","pages":"2610590"},"PeriodicalIF":1.7,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12758298/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145878226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
PI3Kγ inhibition drives M1 macrophage differentiation and synergizes with PD-L1 blockade to improve survival in poorly immunogenic head and neck squamous cell carcinoma. PI3Kγ抑制驱动M1巨噬细胞分化,并与PD-L1阻断协同提高免疫原性差的头颈部鳞状细胞癌的生存率。
IF 4.6 4区 医学
Cancer Biology & Therapy Pub Date : 2026-12-31 Epub Date: 2025-12-22 DOI: 10.1080/15384047.2025.2600701
Pete P Jordanides, Sushmitha Jagadeesha, Puja Upadhaya, Nathan M Ryan, Kelvin Anderson, Felipe F Lamenza, Suvekshya Shrestha, Arham Siddiqui, Anna R Bopp, Sherefuddin H Pracha, Peyton Roth, Reegan Kehres, Xiaokui Mo, Steve Oghumu
{"title":"PI3Kγ inhibition drives M1 macrophage differentiation and synergizes with PD-L1 blockade to improve survival in poorly immunogenic head and neck squamous cell carcinoma.","authors":"Pete P Jordanides, Sushmitha Jagadeesha, Puja Upadhaya, Nathan M Ryan, Kelvin Anderson, Felipe F Lamenza, Suvekshya Shrestha, Arham Siddiqui, Anna R Bopp, Sherefuddin H Pracha, Peyton Roth, Reegan Kehres, Xiaokui Mo, Steve Oghumu","doi":"10.1080/15384047.2025.2600701","DOIUrl":"10.1080/15384047.2025.2600701","url":null,"abstract":"<p><strong>Background: </strong>Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer globally with high mortality rates, highlighting the urgent need for novel therapeutic strategies. We investigated the efficacy of combining phosphoinositide 3-kinase gamma (PI3Kγ) inhibition with programmed death-ligand 1 (PD-L1) blockade in a poorly immunogenic HNSCC model.</p><p><strong>Materials and methods: </strong>Mouse bone marrow-derived macrophages (BMDMs) were differentiated and polarized in the presence or absence of the PI3Kγ inhibitor IPI-549 or culture supernatants from MOC2 cells treated with or without IPI-549. MOC2 cells were orthotopically injected into C57BL/6 mice, and treated with anti-PD-L1, IPI-549, combined anti-PD-L1 and IPI-549 or vehicle control. Tumor burden, survival, and immunological responses were evaluated.</p><p><strong>Results and conclusion: </strong>Dual inhibition of PI3Kγ (using IPI-549) and PD-L1 demonstrated nearly significant reduction in primary tumor burden and significantly increased survival compared to single or control treatments. PI3Kγ inhibition promoted macrophage differentiation toward an antitumoral M1 phenotype. In the bone marrow, dual therapy significantly increased MHC-II expression across various myeloid cell subsets and effectively normalized myelopoiesis. Notably, combination therapy increased CD8+ T-cell infiltration into tumors while decreasing T-cell exhaustion marker (LAG-3, CTLA-4, and TIM-3) and protumoral cytokine (IL-4). Combined PI3Kγ and PD-L1 inhibition offers a promising strategy for treating poorly immunogenic HNSCC by simultaneously targeting multiple immunosuppressive mechanisms. These findings provide a strong rationale for combining PI3Kγ and PD-L1 inhibitors as a therapeutic strategy for poorly immunogenic HNSCC, potentially improving clinical outcomes for patients.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"27 1","pages":"2600701"},"PeriodicalIF":4.6,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12758254/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145809559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Bilateral hypertensive retinopathy (grade 4): Case report and review of the literature on intravitreal injection anti-VEGF therapy. 双侧高血压性视网膜病变(4级):玻璃体内注射抗vegf治疗1例及文献回顾
IF 3.5 4区 医学
Clinical and Experimental Hypertension Pub Date : 2026-12-31 Epub Date: 2025-12-23 DOI: 10.1080/10641963.2025.2604831
Yang Jianjun
{"title":"Bilateral hypertensive retinopathy (grade 4): Case report and review of the literature on intravitreal injection anti-VEGF therapy.","authors":"Yang Jianjun","doi":"10.1080/10641963.2025.2604831","DOIUrl":"10.1080/10641963.2025.2604831","url":null,"abstract":"<p><strong>Objective: </strong>To introduce bilateral hypertensive retinopathy (HR) (grade 4) complicated with macular edema (ME) patients with binocular intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) treatment.</p><p><strong>Methods: </strong>Three cases of hypertensive retinopathy were observed. The fundus examination was consistent with HR (grade 4). The patients received anti-VEGF intraocular injection.</p><p><strong>Results: </strong>The patient's ME and optic nerve edema were significantly reduced, visual acuity was significantly improved, and a case of secondary choroidal neovascularization (CNV) in the fundus of HR (grade 4) was also noted.</p><p><strong>Conclusions: </strong>The use of intravitreal anti-VEGF agents in stage IV hypertensive retinopathy appears satisfactory but not perfect. In severe cases with vitreous hemorrhage, early injection avoids vitrectomy.</p>","PeriodicalId":10333,"journal":{"name":"Clinical and Experimental Hypertension","volume":"48 1","pages":"2604831"},"PeriodicalIF":3.5,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145818438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Comments on "efficacy of mindfulness-based interventions on perinatal mood disorders and neonatal outcomes: a systematic review and meta-analysis". 对“基于正念的干预对围产期情绪障碍和新生儿结局的疗效:一项系统回顾和荟萃分析”的评论。
IF 2 3区 医学
Journal of Psychosomatic Obstetrics & Gynecology Pub Date : 2026-12-31 Epub Date: 2025-12-29 DOI: 10.1080/0167482X.2025.2611110
Archana Mehta, Sushma Narsing Katkuri, Varshini Vadhithala, Arun Kumar, Sushma Verma, Dhanya Dedeepya
{"title":"Comments on \"efficacy of mindfulness-based interventions on perinatal mood disorders and neonatal outcomes: a systematic review and meta-analysis\".","authors":"Archana Mehta, Sushma Narsing Katkuri, Varshini Vadhithala, Arun Kumar, Sushma Verma, Dhanya Dedeepya","doi":"10.1080/0167482X.2025.2611110","DOIUrl":"https://doi.org/10.1080/0167482X.2025.2611110","url":null,"abstract":"","PeriodicalId":50072,"journal":{"name":"Journal of Psychosomatic Obstetrics & Gynecology","volume":"47 1","pages":"2611110"},"PeriodicalIF":2.0,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145858930","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}
引用次数: 0
Bile salt hydrolase activity as a rational target for MASLD therapy. 胆汁盐水解酶活性作为MASLD治疗的合理靶点。
IF 11 1区 医学
Gut Microbes Pub Date : 2026-12-31 Epub Date: 2026-01-02 DOI: 10.1080/19490976.2025.2608437
Elizabeth V Jones, Yongtao Wang, Wenchao Wei, James C Reed, Snehal N Chaudhari, Darrick K Li, Jerome Boursier, Sonja Lang, Münevver Demir, Anna Mae Diehl, Andrew S Allegretti, Bernd Schnabl, Raymond T Chung, A Sloan Devlin
{"title":"Bile salt hydrolase activity as a rational target for MASLD therapy.","authors":"Elizabeth V Jones, Yongtao Wang, Wenchao Wei, James C Reed, Snehal N Chaudhari, Darrick K Li, Jerome Boursier, Sonja Lang, Münevver Demir, Anna Mae Diehl, Andrew S Allegretti, Bernd Schnabl, Raymond T Chung, A Sloan Devlin","doi":"10.1080/19490976.2025.2608437","DOIUrl":"10.1080/19490976.2025.2608437","url":null,"abstract":"<p><p>Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease in the United States, yet therapeutic options remain limited. Emerging evidence implicates the gut‒liver axis and intestinal permeability in disease pathogenesis. Previous studies in animal models and human cell culture indicated that bile salt hydrolases (BSHs), which are gut bacterial enzymes that deconjugate host-derived bile acids, damage intestinal barrier integrity and cause liver damage through the generation of unconjugated bile acids (UBAs). However, the relevance of these findings to MASLD patients is unknown. Here, we demonstrate that BSH activity is elevated in fecal samples from MASLD patients with advanced liver fibrosis and correlates with reduced fecal bile acid levels, which is consistent with a proposed model of increased intestinal permeability during MASLD progression. Through anaerobic culturing and activity-guided screening, we identify diverse BSH-active bacteria from patient fecal samples, suggesting broad microbial contributions to bile acid deconjugation in MASLD patients. Importantly, small-molecule BSH inhibitors suppressed BSH activity in both fecal communities and monocultures from MASLD patients without affecting bacterial viability. These findings indicate that BSH activity is a microbial function associated with MASLD progression and suggest that BSH inhibitors could be developed as a microbiome-targeted strategy for MASLD treatment.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"18 1","pages":"2608437"},"PeriodicalIF":11.0,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12773562/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145888261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Role of callose accumulation in the suppression of calcium-deficiency-induced necrosis in Arabidopsis thaliana cotyledons. 胼胝质积累在抑制钙缺乏诱导的拟南芥子叶坏死中的作用
IF 3.6
Plant signaling & behavior Pub Date : 2026-12-31 Epub Date: 2026-01-06 DOI: 10.1080/15592324.2025.2607237
Yusuke Shikanai, Takehiro Kamiya, Akihiro Saito, Kyoko Higuchi, Toru Fujiwara
{"title":"Role of callose accumulation in the suppression of calcium-deficiency-induced necrosis in <i>Arabidopsis thaliana</i> cotyledons.","authors":"Yusuke Shikanai, Takehiro Kamiya, Akihiro Saito, Kyoko Higuchi, Toru Fujiwara","doi":"10.1080/15592324.2025.2607237","DOIUrl":"https://doi.org/10.1080/15592324.2025.2607237","url":null,"abstract":"<p><p>Calcium (Ca) deficiency symptoms, such as blossom end rot in tomato and tip burn in lettuce, are among the most serious physiological disorders in agriculture. A common feature of this disorder is the expansion of necrosis. However, mechanisms underlying Ca-deficiency-induced necrosis remain poorly understood. We previously identified callose synthase genes (<i>GSL1</i>, <i>GSL8</i>, <i>GSL10</i>) as the causal genes of low-Ca-sensitive <i>Arabidopsis thaliana</i> mutants, which exhibit severe cell death in true leaves and reduced callose accumulation in cotyledons under low-Ca conditions. This raises the question of whether callose accumulation suppresses the spread of cell death. To clarify their relationship within the same organ, we examined callose deposition and cell death in the cotyledons of the <i>gsl10</i> mutant. Although the <i>gsl10</i> mutant showed a comparable level of total cell death to wild-type plants, the necrotic spots were larger. Furthermore, the largest necrotic spots were typically found at the cotyledon tip, but this tendency was weaker in <i>gsl10</i> mutant. Collectively, our results suggest that callose does not suppress the initiation of cell death but rather limits its propagation, thereby leading to the formation of a characteristic necrotic pattern preferentially occurring at the cotyledon tip.</p>","PeriodicalId":94172,"journal":{"name":"Plant signaling & behavior","volume":"21 1","pages":"2607237"},"PeriodicalIF":3.6,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145914304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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