Molecular Medicine最新文献

{"title":"Dysfunctional glycolysis-UCP2-fatty acid oxidation promotes CTLA4^intFOXP3^int regulatory T-cell production in rheumatoid arthritis.","authors":"Jiawen Han, Zhongyang Zhou, Hongxia Wang, Yuxin Chen, Wuguo Li, Meiqin Dai, Jing Bian, Erming Zhao, Jiaying He, Xinyao Zhang, Huanfa Yi, Lan Shao","doi":"10.1186/s10020-025-01372-6","DOIUrl":"10.1186/s10020-025-01372-6","url":null,"abstract":"","PeriodicalId":18813,"journal":{"name":"Molecular Medicine","volume":"31 1","pages":"310"},"PeriodicalIF":6.4,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12512393/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145258770","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":"WGX50 attenuates radiation enteritis by targeting ferroptosis and redox homeostasis via EGFR.","authors":"Zhijing Yin, Guanjun Chen, Yunqing Liu, Yiqi Tan, Jingyi Tang, Ganghua Zhang, Dongqing Wei, Yuxing Zhu, Ke Cao","doi":"10.1186/s10020-025-01375-3","DOIUrl":"10.1186/s10020-025-01375-3","url":null,"abstract":"<p><strong>Background: </strong>Radiation enteritis (RE) is a common complication in patients undergoing abdominal and pelvic radiotherapy. Despite the advancements in radiotherapy, effective treatments remain limited. WGX50, a bioactive compound from Sichuan pepper, has shown anti-inflammatory and antioxidant properties. This study investigates the protective effects of WGX50 on RE, focusing on its potential to reduce radiation-induced damage in the intestine.</p><p><strong>Methods: </strong>Network pharmacology and molecular docking were used to identify the molecular targets of WGX50. In vitro, human intestinal epithelial cells (HIEC6) and colon cells (NCM460) were exposed to radiation and treated with WGX50. In vivo, C57BL/6 mice were administered WGX50 prior to radiation exposure. Various assays, including CCK-8, colony formation, flow cytometry, histopathology, and 16S rRNA sequencing, were performed to evaluate cell proliferation, apoptosis, oxidative stress, intestinal damage, and gut microbiota composition. Tissue transcriptome sequencing was conducted to explore differentially expressed genes.</p><p><strong>Results: </strong>In vitro, WGX50 significantly mitigated radiation-induced cell damage, enhanced cell proliferation, and reduced apoptosis at non-toxic concentrations. In vivo, WGX50 treatment preserved intestinal morphology and reduced inflammatory infiltration in irradiated mice. WGX50 also protected goblet cells, maintaining mucin production and epithelial barrier function critical for intestinal homeostasis. Molecular docking, dynamics simulations and surface plasmon resonance (SPR) revealed stable binding of WGX50 to Epidermal Growth Factor Receptor (EGFR), key targets involved in oxidative stress regulation and ferroptosis inhibition. Mechanistically, WGX50 upregulated the EGFR-SLC7A11-GPX4 axis, suppressing ferroptosis and protecting intestinal cells. Additionally, 16S rRNA sequencing showed that WGX50 mitigated radiation-induced gut microbiota dysbiosis, preserving microbial diversity and promoting beneficial bacterial populations.</p><p><strong>Conclusion: </strong>WGX50 demonstrates potent radioprotective effects by reducing oxidative stress, suppressing ferroptosis, and maintaining intestinal homeostasis, including goblet cell function and gut microbiota composition. These findings support WGX50's potential as a novel therapeutic agent for the prevention and treatment of radiation enteritis.</p>","PeriodicalId":18813,"journal":{"name":"Molecular Medicine","volume":"31 1","pages":"309"},"PeriodicalIF":6.4,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12505694/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145251893","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":"CAMKK2 restored mitochondrial dynamics homeostasis to alleviate pulmonary fibrosis via AMPK/PGC-1α signaling pathway in lung fibroblasts.","authors":"Yanlin Zhou, Yuqi Wang, Mengyuan Wang, Bin Li, Kai Xu, Xiaoyue Pan, Zhongzheng Li, Qiwen Wang, Wanyu He, Jiaojiao Pang, Yingchun Guo, Yuqing Zhang, Koji Sakamoto, Juntang Yang, Lan Wang, Guoying Yu","doi":"10.1186/s10020-025-01373-5","DOIUrl":"10.1186/s10020-025-01373-5","url":null,"abstract":"","PeriodicalId":18813,"journal":{"name":"Molecular Medicine","volume":"31 1","pages":"308"},"PeriodicalIF":6.4,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12502149/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145239320","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":"LncRNA CASC19 promotes pancreatic cancer progression by increasing PSPC1 protein stability and facilitating the oncogenic PSPC1/ β-Catenin pathway.","authors":"Moumita Mukherjee, Swati Ghosh, Atanu Maity, Sukanta Ray, Hemabha Saha, Ranjit Prasad Bahadur, Srikanta Goswami","doi":"10.1186/s10020-025-01363-7","DOIUrl":"10.1186/s10020-025-01363-7","url":null,"abstract":"","PeriodicalId":18813,"journal":{"name":"Molecular Medicine","volume":"31 1","pages":"305"},"PeriodicalIF":6.4,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12482102/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145191589","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":"NET degradation attenuates ricin-induced acute lung injury and protects mice from ARDS.","authors":"Anita Sapoznikov, Yentl Evgy, Liat Fux, Ilya Ruderfer, Yakir Nataf, Yael Hayon, Shay Zamin, Roey Mizrachi, Rachel Pessah, Yoav Gal, Alon Ben-David, Noam Erez, Reut Falach","doi":"10.1186/s10020-025-01370-8","DOIUrl":"10.1186/s10020-025-01370-8","url":null,"abstract":"<p><strong>Background: </strong>Neutrophils are critical first responders of the innate immune system, rapidly recruited to sites of infection or sterile injury. Upon activation by pathogen- or damage-associated molecular patterns, neutrophils initiate antimicrobial responses, including cytokine release, phagocytosis, and the formation of neutrophil extracellular traps (NETs). While NETosis plays a protective role, excessive NET formation can exacerbate inflammation and tissue damage. Pulmonary exposure to ricin, a potent toxin derived from Ricinus communis, results in acute lung injury characterized by neutrophil infiltration, cytokine production, vascular leakage, and pulmonary edema. This study investigated the contribution of NETosis to ricin-induced lung pathology and explored the therapeutic potential of targeting NETosis with a long acting recombinant DNase I (PRX-119) to attenuate lung injury.</p><p><strong>Methods: </strong>CD1 outbreed mice were pulmonary exposed to ricin, and bronchoalveolar lavage fluid (BALF) and lung tissues were collected at various time points post-exposure. NETosis was assessed by immunofluorescence and Western blot analysis of markers, including peptidyl arginine deiminase 4 (PAD4), citrullinated histone H3 (citH3) and myeloperoxidase (MPO). Therapeutic intervention included administration of a NET-degrading DNase agent in combination with an anti-ricin antibody. Cell-free DNA levels, NETosis markers, neutrophil infiltration, lung histopathology, vascular permeability and the expression of pro- and anti-inflammatory mediators were evaluated. Weight loss and survival were also monitored and compared between anti-ricin monotherapy and combined anti-ricin and plant-produced human recombinant long acting (LA) DNase I (PRX-119), a novel NET degradation therapy.</p><p><strong>Results: </strong>Ricin exposure led to elevated pulmonary levels of PAD4, citH3 and MPO, accompanied by extensive NET formation in both BALF and lung tissue. Mice receiving combined therapy with a newly developed DNase I - based agent (PRX-119) and an anti-ricin antibody treatment exhibited significantly improved survival and reduced weight loss compared to antibody monotherapy. The combined treatment not only significantly reduced NETosis markers, but also improved lung histopathology, reduced vascular leakage and pulmonary edema and altered the levels of proteins involved with pro- or anti-inflammatory effects, Dkk-1, CD93 and Periostin.</p><p><strong>Conclusions: </strong>These findings demonstrate for the first time that NETosis plays a significant pathological role in ricin-induced lung injury. Moreover, they underscore the therapeutic potential of combining advanced NET-degrading agents, specifically PRX-119, an advanced DNAse I under development, with toxin-neutralizing antibodies as a promising strategy to reduce acute lung damage and enhance clinical outcomes.</p>","PeriodicalId":18813,"journal":{"name":"Molecular Medicine","volume":"31 1","pages":"304"},"PeriodicalIF":6.4,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12481763/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145191631","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":"LAG-3 palmitoylation-inducing dysfunction of decidual CD4⁺T cells is associated with recurrent pregnancy loss.","authors":"Liyuan Cui, Fengrun Sun, Xinhang Meng, Yujie Luo, Jinfeng Qian, Songcun Wang","doi":"10.1186/s10020-025-01361-9","DOIUrl":"10.1186/s10020-025-01361-9","url":null,"abstract":"<p><p>Recurrent pregnancy loss (RPL) profoundly impacts not only the physical health but also the psychological well-being of women. Despite its profound effects, the underlying pathophysiological mechanisms of RPL remain largely elusive, with few discernible warning signs. Lymphocyte activation gene-3 (LAG-3) is a crucial immune checkpoint that modulates immune responses during infection and tumor. In the present study, we examined the expression of LAG-3 on CD4⁺T cells during pregnancy via cytometry by time-of-flight and flow cytometry. Our findings revealed a higher frequency of LAG-3⁺ decidual CD4⁺T (dCD4⁺T) cells in response to trophoblasts during normal pregnancy. This specific LAG-3⁺ subset of dCD4⁺T cells was found to produce a greater number of anti-inflammatory cytokines. Notably, blocking LAG-3 was highly effective in inhibiting the production of anti-inflammatory cytokines, which is detrimental to the maintenance of pregnancy. A decrease in the number of LAG-3⁺dCD4⁺T cells was correlated with miscarriage. Interestingly, the RNA level of LAG-3 (data analyzed from the two published single-cell databases) remained stable in RPL. Palmitoylation might play a role in regulating LAG-3 expression during RPL, as the palmitoylation of LAG-3⁺dCD4⁺T cells was increased in RPL. Additionally, the general palmitoylation inhibitor 2-bromopalmitate was found to upregulate LAG-3 expression on dCD4⁺T cells both in vitro and in vivo. Collectively, these findings highlighted the significant roles of LAG-3 in regulating the function of dCD4⁺T cell and maintaining normal pregnancy. Furthermore, they suggested that lower LAG-3 expression on dCD4⁺T cells could serve as a potential biomarker for diagnosis of RPL.</p>","PeriodicalId":18813,"journal":{"name":"Molecular Medicine","volume":"31 1","pages":"298"},"PeriodicalIF":6.4,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12482660/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145192089","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":"APP SUMOylation prevents BACE1 cleavage of APP and increases BACE1 degradation to promote the nonamyloidogenic pathway.","authors":"Yen-Chen Liu, Wei-Lun Hsu, Yun-Li Ma, Chung-Yao Yin, Kuang-Min Cheng, Eminy H Y Lee","doi":"10.1186/s10020-025-01354-8","DOIUrl":"10.1186/s10020-025-01354-8","url":null,"abstract":"","PeriodicalId":18813,"journal":{"name":"Molecular Medicine","volume":"31 1","pages":"301"},"PeriodicalIF":6.4,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12482303/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145192105","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":"Fundamental prognostic difference of ATM gene mutation and deletion in newly diagnosed mantle cell lymphoma.","authors":"Ales Obr, Diana Malarikova, Eva Kriegova, Helena Urbankova, Zuzana Zemanova, Jirina Manakova, Anna Petrackova, Michaela Vatolikova, Adela Berkova, Kristina Forsterova, Tomas Furst, Andrea Hruskova, Patrik Flodr, Veronika Hanackova, Vit Prochazka, Tomas Papajik, Marek Trneny, Pavel Klener","doi":"10.1186/s10020-025-01376-2","DOIUrl":"10.1186/s10020-025-01376-2","url":null,"abstract":"<p><strong>Background: </strong>Previous studies have suggested that, after acquisition of t(11;14), mantle cell lymphoma (MCL) pathogenesis may proceed via several different genetic second hits, which may shape different mutational profiles of clinically manifest lymphoma. The most prevalent second hit in MCL includes ATM aberrations, accounting for about half of patients with newly diagnosed MCL. As ATM and TP53 mutations tend to be exclusive in MCL, we retrospectively analyzed the prognostic role of ATM deletions and/or mutations in patients with newly diagnosed MCL, both in the entire cohort and in a subcohort of patients with wild-type TP53.</p><p><strong>Methods: </strong>To investigate deletions and mutations of ATM and TP53 in newly diagnosed MCL, we used fluorescence in situ hybridization and next-generation sequencing. To assess relationships between variables, non-parametric (Spearman) and chi-square tests were used. The Kruskal-Wallis test was used to analyze differences in continuous variables between two groups of patients. For survival analyses, the standard Kaplan-Meier estimator and log-rank test were employed. Univariate and multivariate Cox proportional hazard models were used to examine the prognostic value of various factors on patient survival.</p><p><strong>Results: </strong>We analyzed 187 patients with MCL (a median follow-up of 3.6 years). Eighty-one (43%) and 75 (40%) patients had ATM and TP53 aberrations, respectively. Of note, three (9%) patients with mutated ATM harbored a germline mutation. Patients with TP53 aberration had shorter survival rates. Although ATM deletion did not correlate with progression-free survival (PFS) in the entire cohort, it was associated with shorter PFS (hazard ratio 2.25, p = 0.01) in patients with wild-type TP53. A higher frequency of ATM deletion correlated with shorter PFS. Patients with ATM mutation (and wild-type TP53) had a trend toward better PFS (albeit not statistically significant). Moreover, patients with a higher variant allele frequency of ATM mutation tended to have longer PFS.</p><p><strong>Conclusions: </strong>ATM deletion is an important predictor of prognosis in MCL patients and should be routinely examined, especially in those with wild-type TP53. In contrast, an isolated ATM mutation may predict a better prognosis in the context of standard immunochemotherapy.</p>","PeriodicalId":18813,"journal":{"name":"Molecular Medicine","volume":"31 1","pages":"306"},"PeriodicalIF":6.4,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12481964/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145192087","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":"Selective inhibition of BRAF and CRAF sensitizes NF1-deficient malignant peripheral nerve sheath tumors to MEK inhibitors.","authors":"Jiawan Wang, Arnab Sarkar, Natalia Garcia, Lindy Zhang, Ana Calizo, Alla Lisok, Katia Campos, Funan He, Nishanth Punjaala, Teresa Marple, Kai Pollard, Siyuan Zheng, Calixto-Hope G Lucas, Vesselina G Cooke, Christine A Pratilas, Angelina V Vaseva","doi":"10.1186/s10020-025-01353-9","DOIUrl":"10.1186/s10020-025-01353-9","url":null,"abstract":"","PeriodicalId":18813,"journal":{"name":"Molecular Medicine","volume":"31 1","pages":"303"},"PeriodicalIF":6.4,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12482338/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145191661","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":"Genomic medicine in hepatology: mechanisms and liver treatment strategies.","authors":"D S Kozlov, S Rodimova, P Filatov, A Mozherov, P S Timashev, M V Zyuzin, D S Kuznetsova","doi":"10.1186/s10020-025-01358-4","DOIUrl":"10.1186/s10020-025-01358-4","url":null,"abstract":"","PeriodicalId":18813,"journal":{"name":"Molecular Medicine","volume":"31 1","pages":"302"},"PeriodicalIF":6.4,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12482204/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145192162","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}