BMC Medicine最新文献

{"title":"Inhibition of GCKIII kinases STK25 and MST3 mitigates organ lipotoxicity and enhances metabolic resilience under nutritional stress.","authors":"Emma Andersson, Xiangdong Gongye, Emmelie Cansby, Jingjing Zhang, Mara Caputo, Bernice Asiedu, Viktor Garellick, Sheri Booten, Sue Murray, Ferran Font-Gironès, Johan Ruud, Dan Emil Lind, Manoj Amrutkar, Brian W Howell, Ingrid Wernstedt Asterholm, Margit Mahlapuu","doi":"10.1186/s12916-025-04359-6","DOIUrl":"10.1186/s12916-025-04359-6","url":null,"abstract":"<p><strong>Background: </strong>Obesity has reached pandemic proportions, highlighting the urgent need for continued research to uncover the molecular mechanisms governing lipid homeostasis and ectopic fat deposition in overnutrition. Our recent translational studies demonstrated that STE20-type kinases STK25 and MST3 associate with intracellular lipid droplets and play a pivotal role in regulating the dynamic balance between fat storage and utilization. This study aimed to assess the in vivo effects of the combined inhibition of STK25 and MST3 in obese mice.</p><p><strong>Methods: </strong>We performed phenotypic characterization in three cohorts of mice fed a high-fat diet: (1) mice with genetic ablation of Stk25, (2) mice treated with Mst3-targeting antisense oligonucleotide (ASO), and (3) mice depleted of both STK25 and MST3 by injecting Stk25^-/- mice with Mst3 ASO. Whole-body metabolic physiology and organ lipotoxicity were examined in the STK25- and/or MST3-deficient mice compared with their respective controls by using histological assessments, immunofluorescence microscopy, molecular profiling, and biochemical assays.</p><p><strong>Results: </strong>We found that the inactivation of STK25 and MST3, either individually or in combination, provided equal protection against ectopic fat accumulation and associated lipotoxic damage in the liver, kidney, and skeletal muscle of obese mice. Strikingly, high-fat diet-fed STK25/MST3-deficient mice, but not mice lacking only one kinase, displayed reduced body and fat mass gain, which was accompanied by markedly increased abundance of thermogenesis markers in the brown adipose tissue (BAT).</p><p><strong>Conclusions: </strong>Dual inhibition of STK25 and MST3 in mice mitigates obesity-triggered lipotoxic injury to metabolic tissues and elevates indicators of BAT thermogenic capacity.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"518"},"PeriodicalIF":8.3,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12455811/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145124192","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}

{"title":"Retraction Note: NLRC5 exerts anti-endometriosis effects through inhibiting ERβ-mediated inflammatory response.","authors":"Bao Guo, Haiqing Zhu, Chengwei Xiao, Jing Zhang, Xiaojing Liu, Yuan Fang, Bing Wei, Junhui Zhang, Yunxia Cao, Lei Zhan","doi":"10.1186/s12916-025-04395-2","DOIUrl":"10.1186/s12916-025-04395-2","url":null,"abstract":"","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"516"},"PeriodicalIF":8.3,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12449793/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091236","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}

{"title":"Burden of bacterial antimicrobial resistance 1990-2021 in China: a systematic analysis for the global burden of disease study 2021.","authors":"Yifei Chen, Jinxi Li, Yanhong Gong, Xiaoxv Yin","doi":"10.1186/s12916-025-04333-2","DOIUrl":"10.1186/s12916-025-04333-2","url":null,"abstract":"<p><strong>Background: </strong>China is confronted with a severe burden of antimicrobial resistance (AMR), and to date, there has been no comprehensive estimate of the historical trend of the AMR burden in China.</p><p><strong>Methods: </strong>Data on AMR were collected by the Global Antimicrobial Resistance Burden study 1990-2021. Logistic regression, polynomial models, stacked ensemble models, spatiotemporal Gaussian regression models, and mixed-effects meta-regression models are incorporated into the modeling framework to fit the burden of AMR and estimate the number of deaths and disability-adjusted life-years (DALYs) attributable to and associated with AMR in two counterfactual scenarios.</p><p><strong>Results: </strong>In 2021, it was estimated that 711,852 (95% uncertainty interval [UI] (586,447-837,256) deaths were associated with bacterial AMR in China, including 160,268 (132,375-188,160) deaths attributable to bacterial AMR. From 1990 to 2021, the number of deaths attributable to AMR among children under 5 years old declined by 95%, while that among the elderly aged 65 and above increased by 68%. Among the 12 infectious syndromes, the top three with the largest number of deaths attributed to AMR in 2021 were bloodstream infections (74,119), lower respiratory tract infections (60,839), and peritoneal and intra-abdominal infections (11,827). Among them, bloodstream infections were the infectious syndrome with the greatest increase in the number of deaths during the study period. In 2021, the pathogen with the highest number of deaths attributed to AMR was Staphylococcus aureus (39,643), and the one with the greatest increase in attributed deaths was Staphylococcus aureus, with an increase of 20,774 (16,880-24,668). In 2021, the pathogen-drug combination causing the highest number of AMR-attributed deaths was methicillin-resistant Staphylococcus aureus (26,023), and the pathogen with the highest annualized rate of change in attributed deaths over 31 years was third-generation cephalosporin-resistant Acinetobacter baumannii (17.5%).</p><p><strong>Conclusions: </strong>Bacterial antimicrobial resistance in China was a serious threat to public health, especially for elderly people. Meanwhile, intervention measures such as popularizing vaccination, reducing the misuse of antibiotics, and developing new antibiotics should be combined to address this significant health threat.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"517"},"PeriodicalIF":8.3,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12447600/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145085126","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}

{"title":"Spatiotemporal subtypes of brain and spinal cord atrophy in neuromyelitis optica spectrum disorders and multiple sclerosis.","authors":"Zhizheng Zhuo, Xiaolu Xu, Siyao Xu, Shi Yao, Jinyuan Weng, Fuqing Zhou, Tiantian Hua, Jun Sun, Dan Cheng, Guanmei Cao, Xinghu Zhang, Fudong Shi, Tielin Yang, Sven Haller, Andre Altmann, Yuehua Li, Decai Tian, Yunyun Duan, Yaou Liu","doi":"10.1186/s12916-025-04366-7","DOIUrl":"10.1186/s12916-025-04366-7","url":null,"abstract":"<p><strong>Background: </strong>Neuromyelitis optica spectrum disorders (NMOSD) and multiple sclerosis (MS) are autoimmune demyelinating diseases with overlapping clinical features but distinct patterns of brain and spinal cord atrophy. The precise atrophy subtypes specific to each disease remain elusive. This study aimed to identify shared and distinct atrophy subtypes in NMOSD and MS, using neuroimaging to explore their clinical significance and potential implications for tailored treatment strategies.</p><p><strong>Methods: </strong>Clinical and MRI data of 278 AQP4 + NMOSD and 391 MS patients were retrospectively and prospectively collected, alongside 1,065 healthy controls. 3D T1-weighted image derived structural measurements were used in a Subtype and Stage Inference model, to identify distinct brain and spinal cord atrophy subtypes of NMOSD and MS. The clinical characteristics of disease atrophy subtypes and clinical associations of atrophy stage were investigated.</p><p><strong>Results: </strong>The results showed that in NMOSD, three atrophy subtypes were identified: (1) cortical subtype with severe cognitive and physical disability; (2) spinal cord subtype with high number of relapses; and (3) cerebellum subtype with a favorable prognosis. In MS, three atrophy subtypes were identified: (1) cortical subtype featuring severe cognitive decline; (2) spinal cord subtype featuring high number of relapses; and (3) subcortical subtype featuring severe physical disability. Advanced stages in MS spinal cord and subcortical atrophy subtypes were associated with severe physical disability and cognitive decline, while advanced stage in all MS subtypes correlated with disability worsening.</p><p><strong>Conclusions: </strong>These novel imaging subtypes in NMOSD and MS may help interpret disease heterogeneity, develop stratified management, and assess prognosis.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"514"},"PeriodicalIF":8.3,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12403954/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144943106","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}

{"title":"Immune checkpoint inhibitors use in liver transplantation for hepatocellular carcinoma: a global cohort study.","authors":"Delin Ma, Pengcheng Wei, Qian Cheng, Jialing Hao, Zuyin Li, Zhuomiaoyu Chen, Wenzai Shi, Zhigao Yuan, Chen Lo, Yongjing Luo, Liyi Qiao, Jie Gao, Jiye Zhu, Zhao Li","doi":"10.1186/s12916-025-04352-z","DOIUrl":"10.1186/s12916-025-04352-z","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC) remains a major contributor to global cancer mortality, with liver transplantation (LT) offering curative potential for patients in the early stages. While immune checkpoint inhibitors (ICIs) are effective in managing tumor progression, concerns about graft rejection persist. This study investigates how peri-LT ICIs administration affects rejection rates and survival outcomes in HCC patients.</p><p><strong>Methods: </strong>This global study analyzed 386 HCC patients receiving Peri-LT ICIs therapy, integrating data from a systematic literature review and institutional registries. The risk of graft rejection and survival outcomes were assessed using logistic and Cox regression, along with restricted cubic splines modeling dose-response dynamics.</p><p><strong>Results: </strong>Overall graft rejection rates did not significantly differ between Pre-LT (17.5%) and Post-LT (22.1%) ICI users (P = 0.351); however, Post-LT use was associated with higher rates of graft loss/dysfunction (47.1% vs. 25.9%, P < 0.05) and rejection-related mortality (47.1% vs. 18.5%, P < 0.05). In Pre-LT patients, washout periods >30 days (OR = 0.36, 95% CI: 0.18-0.72, P = 0.004) and >1.5 half-life counts (OR = 0.24, 95% CI: 0.12-0.50, P < 0.001) were associated with reduced rejection risk. Post-LT, high PD-L1 expression on graft tissue correlated with increased rejection risk (P < 0.001). Graft rejection following Pre-LT ICIs was linked to poorer overall survival (HR = 5.17, 95% CI: 2.21-12.24, P < 0.001).</p><p><strong>Conclusions: </strong>With careful management, peri-LT ICIs may be considered for HCC patients. Optimizing washout periods and monitoring graft PD-L1 expression may improve transplant outcomes.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"515"},"PeriodicalIF":8.3,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12403418/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144943028","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}

{"title":"Fecal microbiota transplantation improves bile acid malabsorption in patients with inflammatory bowel disease: results of microbiota and metabolites from two cohort studies.","authors":"Gaochen Lu, Sheng Zhang, Rui Wang, Xia Wu, Yaoyao Chen, Quan Wen, Bota Cui, Faming Zhang, Pan Li","doi":"10.1186/s12916-025-04353-y","DOIUrl":"10.1186/s12916-025-04353-y","url":null,"abstract":"<p><strong>Background: </strong>Bile acid malabsorption (BAM) or bile acid diarrhea (BAD) complicates more than 30% of Crohn's disease (CD), yet no non-invasive biomarker reliably identifies patients who will benefit from fecal microbiota transplantation (FMT). We investigated whether serum 7α-hydroxy-4-cholesten-3-one (C4), a hepatic bile-acid synthesis precursor, can predict BAM and FMT response in inflammatory bowel disease (IBD).</p><p><strong>Methods: </strong>We included 106 pairs of IBD patients treated with FMT from two longitudinal cohorts of prospective trials and 24 matched healthy individuals to identify a multi-omics analysis of microbiota-metabolism and evaluate real-world effectiveness of FMT. Fecal and serum samples before and after FMT along with medical information were collected and detected through 16S rRNA amplicon sequencing and untargeted liquid chromatography mass spectrometry. Mice models were used to preliminarily verify the exacerbation of colitis through administration of primary BAs and treated by FMT.</p><p><strong>Results: </strong>Patients in BAM group tended to achieve sustained higher and stable clinical response (66.67% vs. 49.41%) and remission (52.38% vs. 40.00%) than non-BAM group at 3 months after FMT, along with a significantly decrease of C4 (P < 0.001), improvement of obvious abdominal pain and diarrhea, which was especially obvious in CD patients with ileal resection and ileal /ileocolonic type. Random forest classifiers predicted BAM in IBD patients with 18 or top 4 differential OTUs, showing an area under the curve of 0.92 and 0.83, respectively. Furthermore, results from primary bile acid-induced colitis mice models reinforced these findings.</p><p><strong>Conclusions: </strong>Serum C4 and a minimal gut microbiota may identify IBD patients with BAM who are most likely to achieve durable remission after FMT. These translatable biomarkers can guide precision use of microbiota-directed therapy.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov: NCT01790061 and NCT01793831.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"511"},"PeriodicalIF":8.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12403533/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144943035","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}

{"title":"Shrinking the malaria map in Indonesia: progress of subnational control, elimination, and future strategies.","authors":"Herdiana Herdiana, Hellen Dewi Prameswari, Riskha Tiara Puspadewi, Sri Budi Fajariyani, Ajib Diptyanusa, Minerva Theodora, Dedy Supriyanto, William A Hawley","doi":"10.1186/s12916-025-04355-w","DOIUrl":"10.1186/s12916-025-04355-w","url":null,"abstract":"<p><strong>Background: </strong>Indonesia has a complex pattern of malaria transmission alongside a highly decentralized system of governance. Indonesia applies a subnational elimination strategy to achieve nationwide malaria elimination by 2030. This review describes Indonesia's subnational verification process, assesses progress towards subnational elimination over the past several decades, and explores strategies to accelerate achievement of elimination, including the challenges of high transmission in lowland Papua region and zoonotic malaria in Sumatra and Kalimantan islands.</p><p><strong>Methods: </strong>Published and unpublished data, reports, and grey literature in Indonesian and English from 1950 to 2023 were collected and analyzed. These reports document strategies, geographic coverage, and malaria metrics. Most of the unpublished data and reports are from the Ministry of Health of Indonesia, including the guidelines describing processes for certification of district-level malaria elimination.</p><p><strong>Results: </strong>While the number of malaria cases has fluctuated over the years, cases decreased significantly by 2015 but increased during the Coronavirus disease-19 (COVID-19) pandemic. Nonetheless, as of 2023, 389 of 514 districts and five of 38 provinces had been verified as having no local transmission of malaria, with the most rapid progress observed in western Indonesia. We describe the malaria elimination verification process in detail, including the criteria used and challenges encountered. Malaria cases are now localized in the Papua region, which reports more than 90% of cases in the country. The lowland Papua region experiences high transmission with malaria incidence of over 400 cases per 1000 person-years due to its efficient vectors and high year-round rainfall. Expansion of malaria transmission to highland Papua due to climate change is likely happening. In the west, pockets of transmission persist in remote areas and among mobile and migrant populations. Further, frequent outbreaks occur in malaria-free districts, with two districts now experiencing re-established transmission. In addition, reports of zoonotic Plasmodium knowlesi infections in humans are increasing.</p><p><strong>Conclusions: </strong>Existing interventions will need to be well-managed, and new combinations of interventions implemented if Indonesia is to achieve its goal of malaria elimination by 2030, particularly in high-endemic Papua, which will remain a source of importation of malaria to other regions of Indonesia if malaria there is not eliminated.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"512"},"PeriodicalIF":8.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12403376/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144943129","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}

{"title":"Practice of data sharing plans in clinical trial registrations and concordance between registered and published data sharing plans: a cross-sectional study.","authors":"Jingyi Zhang, Barbara E Bierer, Harriette G C Van Spall, Yingxin Liu, Xuerui Bai, Lehana Thabane, Gregory Y H Lip, Xin Sun, David Moher, Guowei Li","doi":"10.1186/s12916-025-04328-z","DOIUrl":"10.1186/s12916-025-04328-z","url":null,"abstract":"<p><strong>Background: </strong>The International Committee of Medical Journal Editors (ICMJE) recommends that trial authors must specify data sharing plans when trials are registered and published, yet this uptake remains unclear. We aimed to assess the practice of data sharing plans in trial registration platforms and the concordance between registered and published data sharing plans.</p><p><strong>Methods: </strong>We included clinical trials published between 2021 and 2023 in six high-profile journals (The Lancet, The New England Journal of Medicine, JAMA, BMJ, JAMA Internal Medicine, and Annals of Internal Medicine) that enrolled participants no earlier than 2019 and registered on clinical trial platforms. One study outcome was data sharing plans in the trial registration platform, where trials clearly responding a \"yes\" to \"Plan to share\" were considered as planning to share data (including study protocols, statistical analysis plans, analytic codes, and individual participant data). The concordance between registered and published plans to share data was also assessed, which included plans to either share data (Yes/Yes) and not to share data (No/No) in both registration and publications. Univariate analyses were used to assess associations between trial characteristics and registered plans to share data and between trial characteristics and concordance.</p><p><strong>Results: </strong>Of the 383 included registration IDs, only 44.6% (171/383) planned to share data in registration. Trials with drug versus non-drug interventions had increased odds of registering plans to share data (OR = 2.71, 95% CI: 1.63, 4.63). There were seven trial publications, each pooling two trials and having two registration IDs. We selected the registration IDs with a later start date, resulting in 376 trial publications for concordance assessment. Over half (216/376, 57.4%) had discordance between registration and publications. COVID-19-related trials were associated with decreased odds of data sharing concordance (OR = 0.59, 95% CI: 0.37, 0.91). Additionally, significant discordance was consistently found in statistical analysis plans or study protocols, analytic codes, and individual participant data.</p><p><strong>Conclusions: </strong>Most registered trials do not specify plans to share data. More than half of published trials have data sharing discordance between registration and publication. Efforts are required to improve the reporting and reliability of plans to share clinical trial data.</p><p><strong>Trial registration: </strong>This study was registered on the Open Science Framework ( https://osf.io/k6etb ).</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"510"},"PeriodicalIF":8.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12403310/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144942993","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}

{"title":"Proteomics and metabolomics studies in pigmented villonodular synovitis uncover the regulation of monocyte differentiation by the ADGRE5-NF-κB pathway.","authors":"Minghao Ge, Runze Yang, Baojun Xu, Lei Fan, Maosen Xu, Tianhao Xu, Jian Li, Yusheng Li, Meng Gong, Weili Fu","doi":"10.1186/s12916-025-04358-7","DOIUrl":"10.1186/s12916-025-04358-7","url":null,"abstract":"<p><strong>Background: </strong>Pigmented villonodular synovitis (PVNS), or tenosynovial giant cell tumor (TGCT), is a locally aggressive soft tissue tumor primarily affecting the synovium of joints, particularly the knee. In PVNS, the synovial tissue thickens and becomes aggressive, leading to joint destruction, a process reminiscent of the tissue remodeling seen in autoimmune diseases. Despite being considered benign, PVNS often leads to severe joint damage and has a high recurrence rate following treatment. The underlying molecular mechanisms of PVNS remain poorly understood, necessitating further research to uncover its pathogenesis and identify potential therapeutic targets. This study aims to investigate the pathological mechanisms of PVNS, focusing on the role of metabolic pathways, immune cell infiltration, and osteoclast differentiation in the progression of the disease.</p><p><strong>Methods: </strong>Synovial fluid samples from PVNS patients were subjected to high-throughput proteomic and metabolomic analyses. Differentially expressed proteins (DEPs) and metabolites were identified, and pathway enrichment analysis was performed. Western blot validation and two-way orthogonal partial least squares (O2PLS) analysis confirmed key findings and explored the relationships among identified biomarkers.</p><p><strong>Results: </strong>A total of 156 DEPs and 62 differential metabolites were identified. The \"Osteoclast differentiation signalling\" and \"Nuclear factor-κB (NF-κB) survival signalling\" pathways were significantly upregulated in PVNS samples, with Tumor Necrosis Factor Superfamily Member 11 (TNFSF11), Cathepsin K (CTSK), Adhesion G Protein-Coupled Receptor E5 (ADGRE5), and NF-κB showing marked increases in expression. Metabolomic analysis revealed that \"Linoleic acid metabolism\" and \"Biosynthesis of unsaturated fatty acids\" pathways were enhanced in PVNS, with metabolites such as 13-L-Hydroperoxylinoleic acid and 13-OxoODE being highly expressed. Western blot validation confirmed the elevated levels of ADGRE5, TNFSF11, CTSK, and NF-κB, suggesting a link between enhanced energy metabolism, lipid oxidation, and osteoclast differentiation.  CONCLUSIONS: This study highlights the critical role of metabolic adaptations and immune cell activity in the progression of PVNS. The findings suggest that targeting ADGRE5 and NF-κB could offer new therapeutic strategies for controlling disease progression and reducing joint destruction in PVNS patients. Further research is needed to elucidate this disease's specific regulatory mechanisms and cell types.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"513"},"PeriodicalIF":8.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12403606/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144943094","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}

{"title":"Pregnancy complications as a marker of future cardiovascular disease risk.","authors":"Sonia M Grandi, Graeme Smith","doi":"10.1186/s12916-025-04317-2","DOIUrl":"https://doi.org/10.1186/s12916-025-04317-2","url":null,"abstract":"","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"509"},"PeriodicalIF":8.3,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12398064/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144943134","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}