Journal of molecular medicine (Berlin, Germany)最新文献_第2页

Unravelling deregulated metabolites in seminal plasma of infertile men: a systematic review and bioinformatic analysis. 不育症男性精浆中代谢产物的解除：系统回顾和生物信息学分析。

IF 4.2

Journal of molecular medicine (Berlin, Germany) Pub Date : 2026-09-25 DOI: 10.1007/s00109-026-02719-0

Rafael Santos, Beatriz Marinheiro, Margarida Ramos, Pedro F Oliveira, Pedro O Corda, Margarida Fardilha, Joana Santiago

{"title":"Unravelling deregulated metabolites in seminal plasma of infertile men: a systematic review and bioinformatic analysis.","authors":"Rafael Santos, Beatriz Marinheiro, Margarida Ramos, Pedro F Oliveira, Pedro O Corda, Margarida Fardilha, Joana Santiago","doi":"10.1007/s00109-026-02719-0","DOIUrl":"10.1007/s00109-026-02719-0","url":null,"abstract":"Male infertility is a multifactorial condition accounting for 50% of infertility cases. Although conventional semen analysis remains the standard method for male infertility diagnosis, it fails to explain 30% of the cases and their underlying molecular causes. Metabolomics offers valuable insights into sperm metabolic dysfunction, enabling the identification of deregulated pathways involved in male infertility. Here, a systematic review including metabolomic studies that compare the seminal plasma metabolome of healthy and infertile men was conducted. A literature search was conducted in PubMed, Scopus, and Web of Science databases following PRISMA guidelines. Twenty metabolomic studies published until December 2025 were included and categorized into four groups: asthenozoospermia, oligozoospermia, obesity, and overall male infertility. A total of 284 metabolites were retrieved, of which eleven (down: L-tyrosine, D-fructose, L-valine, phenylalanine, proline, D-glucose, L-alanine, leucine, sorbitol, L-aspartic acid; up: uridine), six (down: D-fructose, glycine, maleic acid, L-valine, proline, and lysine), and ten (down: L-carnitine, L-tyrosine, L-valine, L-alanine, phenylalanine, proline, D-glucose, leucine, malic acid, and citraconic acid) were altered in asthenozoospermia, obesity, and overall infertility groups, respectively. These metabolites were associated with phenylalanine/tyrosine metabolism, fructose and mannose degradation, and β-oxidation of long-chain fatty acids. A bioinformatic analysis of the enzymes possibly involved in these pathways revealed associations with male infertility phenotypes and key sperm functions, including motility, vitality, and energy metabolism. This study provides a list of metabolites altered in the seminal fluid of infertile men, highlighting their potential as biomarkers of male infertility, and gives insights into the metabolic pathways affected in these conditions.","PeriodicalId":520678,"journal":{"name":"Journal of molecular medicine (Berlin, Germany)","volume":"104 1","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149066975","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}

引用次数: 0

Correction to: Constitutive activation of STAT3 is predictive of poor prognosis in human gastric cancer. 更正：STAT3的组成性激活可预测人类胃癌的不良预后。

IF 4.2

Journal of molecular medicine (Berlin, Germany) Pub Date : 2026-09-23 DOI: 10.1007/s00109-026-02712-7

Hua Xiong, Wan Du, Ji-Lin Wang, Ying-Chao Wang, Jie-Ting Tang, Jie Hong, Jing-Yuan Fang

引用次数: 0

MicroRNA-122 as a regulator and biomarker of liver disease. MicroRNA-122作为肝脏疾病的调节因子和生物标志物。

IF 4.2

Journal of molecular medicine (Berlin, Germany) Pub Date : 2026-09-19 DOI: 10.1007/s00109-026-02718-1

Sara Ahmadova, Zofia Wicik, Joanna Mucha, Jeff Palatini, Katarzyna Ziętal, Dagmara Mirowska-Guzel, Adam Przybylkowski, Ceren Eyileten

{"title":"MicroRNA-122 as a regulator and biomarker of liver disease.","authors":"Sara Ahmadova, Zofia Wicik, Joanna Mucha, Jeff Palatini, Katarzyna Ziętal, Dagmara Mirowska-Guzel, Adam Przybylkowski, Ceren Eyileten","doi":"10.1007/s00109-026-02718-1","DOIUrl":"10.1007/s00109-026-02718-1","url":null,"abstract":"MicroRNA-122 (miR-122) is the most abundant liver-specific microRNA, comprising ~ 70% of the hepatic miRNA pool, and a central regulator of lipid metabolism, inflammation, fibrosis, viral replication, and hepatocarcinogenesis. This review synthesizes experimental, clinical, and molecular evidence on the role of miR-122 across the spectrum of liver disease, including metabolic dysfunction-associated fatty liver disease (MAFLD) and steatohepatitis (MASH), drug-induced acute liver injury, hepatitis B and C virus (HBV/HCV) infection, hepatocellular carcinoma (HCC), and colorectal cancer liver metastasis. Mechanistically, miR-122 governs hepatic lipogenesis through the Sirt1/LKB1/AMPK axis, modulates inflammation via LPS/TLR-4/FoxO3 signaling, and exerts tumor-suppressive and antiviral effects through Cyclin G1/p53, HO-1, NDRG3, GALNT10, PEG10, and NEGR1. A recurring theme is the compartment- and stage-dependent behavior of miR-122: hepatic expression declines with disease progression, whereas circulating levels rise with hepatocyte injury, reconciling apparently contradictory reports and underscoring the importance of specimen source and disease stage in biomarker interpretation. We further contrast the etiology-specific regulation of miR-122 in HBV- versus HCV-associated disease, in which epigenetic silencing and interferon-linked mechanisms drive divergent expression. Finally, we critically appraise the failed clinical translation of anti-miR-122 therapeutics (miravirsen, RG-101), highlighting viral resistance, safety liabilities, and the tumor-suppressor paradox that constrains inhibition-based strategies. Collectively, miR-122 emerges as a minimally invasive biomarker and a biologically informative, though therapeutically challenging, target in liver disease.","PeriodicalId":520678,"journal":{"name":"Journal of molecular medicine (Berlin, Germany)","volume":"104 1","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13588829/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149003267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Regulation of pancreatic beta-cell mass and its importance for antidiabetic therapies. 胰腺β细胞质量的调节及其在抗糖尿病治疗中的重要性。

IF 4.2

Journal of molecular medicine (Berlin, Germany) Pub Date : 2026-09-18 DOI: 10.1007/s00109-026-02716-3

Sigurd Lenzen

引用次数: 0

METTL3 mitigates age-related hearing loss by inhibiting NF-κB-mediated inflammatory responses through the m⁶A modification of NFKBIA. METTL3通过对NFKBIA的m6A修饰，抑制NF-κ b介导的炎症反应，从而减轻年龄相关性听力损失。

IF 4.2

Journal of molecular medicine (Berlin, Germany) Pub Date : 2026-09-18 DOI: 10.1007/s00109-026-02714-5

Jingqian Tan, Jia Luo, Liling Li, Dan Chen, Jianyan Wang, Chengyu Ge, Peng Li

{"title":"METTL3 mitigates age-related hearing loss by inhibiting NF-κB-mediated inflammatory responses through the m6A modification of NFKBIA.","authors":"Jingqian Tan, Jia Luo, Liling Li, Dan Chen, Jianyan Wang, Chengyu Ge, Peng Li","doi":"10.1007/s00109-026-02714-5","DOIUrl":"10.1007/s00109-026-02714-5","url":null,"abstract":"Age-related hearing loss (ARHL) is a prevalent and debilitating sensory deficit in the elderly, with chronic inflammation being a key pathogenic driver. The RNA methyltransferase METTL3, a primary mediator of N6-methyladenosine (m6A) modification, has been implicated in various aging-related diseases; however, its functional role and mechanism in ARHL remain poorly defined. ARHL models were established using 12-month-old C57BL/6 mice and by treating HEI-OC1 auditory cells with LPS and D-galactose. Auditory function and cochlear pathology were assessed through auditory brainstem response (ABR) thresholds and hematoxylin-eosin (H&E) staining, respectively. Inflammatory cytokine levels, gene and protein expression, were measured using ELISA, qPCR, Western blotting, and immunofluorescence. The molecular mechanism of METTL3 in inflammation was investigated using m6A RNA methylation quantification kit, RIP-qPCR analysis, and RNA stability assay. We found that both NFKBIA and METTL3 were significantly downregulated in the cochleae of ARHL mice. In HEI-OC1 cells, overexpression of NFKBIA suppressed the NLRP3 inflammasome and the pro-inflammatory NF-κB/IL-6/STAT3 axis. Furthermore, METTL3 overexpression mitigated NF-κB-mediated inflammation, an effect that was significantly attenuated upon NFKBIA knockdown. Mechanistically, METTL3 directly bound to NFKBIA mRNA and enhanced its stability through m6A modification. Critically, in ARHL mice, METTL3 overexpression restored NFKBIA levels, ameliorated hearing loss and cochlear damage, and suppressed the activation of the NLRP3 inflammasome and the NF-κB/IL-6/STAT3 pathway. Collectively, METTL3 mitigated ARHL by downregulating the NF-κB/IL-6/STAT3/NLRP3-mediated inflammatory responses through the enhancement of NFKBIA m6A modification.","PeriodicalId":520678,"journal":{"name":"Journal of molecular medicine (Berlin, Germany)","volume":"104 1","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148993627","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}

引用次数: 0

Prospective associations of premature senescence, inflammation, and MERCSs in the cardioprotective effect of CBD in HFpEF. 在HFpEF中，CBD的心脏保护作用与过早衰老、炎症和mercs的前瞻性关联。

IF 4.2

Journal of molecular medicine (Berlin, Germany) Pub Date : 2026-09-18 DOI: 10.1007/s00109-026-02715-4

Alejandro Silva-Palacios, Alejandra María Zúñiga-Muñoz, Elizabeth Soria-Castro, Edith Álvarez-León, Wylly Ramses García-Niño, Gabriela Navarrete-Anastasio, Dilan Raza, Omar Emiliano Aparicio-Trejo, Ricardo Jair Ramírez-Carreto, Verónica Salas-Venegas, Anahí Chavarría, Roger Alexis Maldonado-Ruíz, Hugo Alves-Figueiredo, Gerardo García-Rivas, Cecilia Zazueta

{"title":"Prospective associations of premature senescence, inflammation, and MERCSs in the cardioprotective effect of CBD in HFpEF.","authors":"Alejandro Silva-Palacios, Alejandra María Zúñiga-Muñoz, Elizabeth Soria-Castro, Edith Álvarez-León, Wylly Ramses García-Niño, Gabriela Navarrete-Anastasio, Dilan Raza, Omar Emiliano Aparicio-Trejo, Ricardo Jair Ramírez-Carreto, Verónica Salas-Venegas, Anahí Chavarría, Roger Alexis Maldonado-Ruíz, Hugo Alves-Figueiredo, Gerardo García-Rivas, Cecilia Zazueta","doi":"10.1007/s00109-026-02715-4","DOIUrl":"10.1007/s00109-026-02715-4","url":null,"abstract":"Heart failure with preserved ejection fraction (HFpEF) remains a clinical challenge lacking effective therapies. While Cannabidiol (CBD) suggests cardioprotective potential, its efficacy and underlying in HFpEF are poorly understood. This study investigated the effects of CBD on a murine model of HFpEF induced by a high-fat diet and L-NAME for 8 weeks. CBD was administered subcutaneously every three days. Hemodynamic performance was assessed via invasive pressure-volume loops, complemented by histological analysis and oxidative stress markers. Cellular senescence, NLRP3-mediated inflammation and Mitochondria-Endoplasmic Reticulum Contact Sites (MERCSs) were evaluated through immunofluorescence, RT-qPCR, and transmission electron microscopy. CBD treatment failed to reduce cardiac hypertrophy but improves cardiac fibrosis and diastolic dysfunction. These improvements were associated with a marked reduction in senescent cells accumulation and on systemic cytokine levels that may be associated with the senescence-associated secretory phenotype (SASP). Notably, CBD suppressed the NLR3-mediated proinflammatory state by preserving inter-organelle distance and MERCSs integrity. Our findings demonstrate, for the first time, that CBD modulates MERCSs communication to regulate senescence and inflammation in HFpEF. These results position CBD as a promising intervention for mitigating the pathology of HFpEF through the regulation of MERCSs, although the signaling pathways involved in this protective mechanism need to be characterized.","PeriodicalId":520678,"journal":{"name":"Journal of molecular medicine (Berlin, Germany)","volume":"104 1","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149003280","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}

引用次数: 0

Correction to: Suppression of OTUD4 protects against myocardialischemia‑reperfusion injury by increasing autophagic fluxand inhibiting apoptosis in cardiomyocytes. 更正：抑制OTUD4通过增加心肌细胞的自噬通量和抑制细胞凋亡来保护心肌缺血再灌注损伤。

IF 4.2

Journal of molecular medicine (Berlin, Germany) Pub Date : 2026-09-16 DOI: 10.1007/s00109-026-02711-8

Xin-Xin Sun, Lin Qi, Ming-Jun Dai, Fang-Lin Lu, Yi-Min Xiao, Wei-Jin Sun, Yu Zhuang

引用次数: 0

Anti-hyperuricemia therapy alleviates diet-induced gut inflammation via AhR-IL-22-signalling. 抗高尿酸血症治疗通过ahr - il -22信号传导缓解饮食诱导的肠道炎症。

IF 4.2

Journal of molecular medicine (Berlin, Germany) Pub Date : 2026-09-04 DOI: 10.1007/s00109-026-02713-6

Soledad Bouquez, Paola López Campos, Macarena Ottobre, Maite Duhalde-Vega

{"title":"Anti-hyperuricemia therapy alleviates diet-induced gut inflammation via AhR-IL-22-signalling.","authors":"Soledad Bouquez, Paola López Campos, Macarena Ottobre, Maite Duhalde-Vega","doi":"10.1007/s00109-026-02713-6","DOIUrl":"10.1007/s00109-026-02713-6","url":null,"abstract":"High-fat diets (HFD) are implicated in metabolic disorders through mechanisms involving hyperuricemia, gut dysbiosis, and intestinal barrier dysfunction. This study investigated the effects of pharmacological uric acid reduction on gut homeostasis in HFD-fed mice. We assessed serum uric acid, gut microbial composition, pro- and anti-inflammatory cytokine expression, intestinal barrier dysfunction markers, and tryptophan metabolism in mice subjected to HFD with or without allopurinol treatment. AhR antagonist CH-223191 was used to provide functional evidence for the role of AhR activation in mediating the observed effects. HFD induced hyperuricemia, microbial dysbiosis characterized by increased Proteobacteria and altered Firmicutes/Bacteroidetes ratios, and elevated pro-inflammatory cytokines (IL-1β, IL-6, TNF-α). These changes correlated with decreased IL-10 and IL-22, increased serum LPS, and systemic inflammation (IL-6, CRP). Allopurinol treatment normalized uric acid levels, restored microbial balance, reduced gut and systemic inflammation, improved intestinal barrier function, and modulated tryptophan metabolism by decreasing IDO1 activity and restoring indole production. Pharmacological blockade of AhR with CH-223191 reversed the anti-inflammatory and barrier-protective effects of allopurinol treatment, providing functional evidence for the role of AhR/IL22 axis in mediating gut protection. Targeting hyperuricemia effectively reverses HFD-induced gut dysbiosis, inflammation, and barrier dysfunction through metabolite-mediated immunoregulatory mechanisms involving the AhR-IL-22 axis. These findings propose uric acid modulation as a promising therapeutic strategy for metabolic and inflammatory gut diseases.","PeriodicalId":520678,"journal":{"name":"Journal of molecular medicine (Berlin, Germany)","volume":"104 1","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148889860","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}

引用次数: 0

Neutrophil extracellular traps in tumor progression: from mechanistic insights and regulatory factors to clinical detection and diagnosis. 中性粒细胞胞外陷阱在肿瘤进展：从机制的见解和调节因素到临床检测和诊断。

IF 4.2

Journal of molecular medicine (Berlin, Germany) Pub Date : 2026-09-01 DOI: 10.1007/s00109-026-02709-2

Yijun Zhang, Zhaoyang Zeng, Wei Xiong, Jiadi Luo, Chunmei Fan

{"title":"Neutrophil extracellular traps in tumor progression: from mechanistic insights and regulatory factors to clinical detection and diagnosis.","authors":"Yijun Zhang, Zhaoyang Zeng, Wei Xiong, Jiadi Luo, Chunmei Fan","doi":"10.1007/s00109-026-02709-2","DOIUrl":"10.1007/s00109-026-02709-2","url":null,"abstract":"Neutrophil extracellular traps (NETs), web-like DNA structures released by neutrophils, were initially recognized as key components of the anti-infective immune response but are now implicated in tumor progression. Tumor cells orchestrate the reprogramming of tumor-associated neutrophils (TANs) and trigger NET formation through paracrine signaling, thereby establishing a \"tumor cell-TAN-NETs\" positive feedback loop. This axis serves not only as a key hub for awakening dormant tumor foci and mediating immune evasion, but also as a core mechanism driving distant metastasis and dictating poor clinical prognosis. Notably, targeted disruption of this axis effectively reverses tumor therapy resistance and significantly sensitizes tumors to radiotherapy, chemotherapy, and immune checkpoint blockade, establishing NETs as novel therapeutic targets poised to overcome the current bottlenecks in cancer treatment. Nevertheless, limitations in detection technologies, prognostic modeling challenges, tumor heterogeneity, and inconsistent research findings constrain clinical translation. Future studies should prioritize optimizing detection methods, conducting rigorous clinical validation, and identifying specific therapeutic targets to accelerate the translational progress of NETs from basic research to clinical practice. This review synthesizes current knowledge on the biological mechanisms, regulatory pathways, and detection approaches of NETs, providing a theoretical basis for their clinical application in precision oncology.","PeriodicalId":520678,"journal":{"name":"Journal of molecular medicine (Berlin, Germany)","volume":"104 1","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148868902","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}

引用次数: 0

L-ICON3 Suppresses Endometriosis in a Murine Model. L-ICON3抑制小鼠子宫内膜异位症

IF 4.2

Journal of molecular medicine (Berlin, Germany) Pub Date : 2026-08-27 DOI: 10.1007/s00109-026-02710-9

Ramanaiah Mamillapalli, Akanksha Garg, Graciela Krikun, Shant Apelian, Shutaro Habata, Rula Atwani, Nimisha Gawde, Zhiwei Hu, Hugh S Taylor

{"title":"L-ICON3 Suppresses Endometriosis in a Murine Model.","authors":"Ramanaiah Mamillapalli, Akanksha Garg, Graciela Krikun, Shant Apelian, Shutaro Habata, Rula Atwani, Nimisha Gawde, Zhiwei Hu, Hugh S Taylor","doi":"10.1007/s00109-026-02710-9","DOIUrl":"10.1007/s00109-026-02710-9","url":null,"abstract":"Endometriosis is a chronic, systemic gynecological disorder that affects 190 million women worldwide. Current treatments consist of hormonal suppression and surgical excision; however, both have considerable side effects and a high risk of recurrence. Here, we report a systemic therapy to treat endometriosis by L-ICON3, a novel chimeric immunoconjugate molecule that binds to tissue factor (TF), which is upregulated in endometriosis. Endometriosis was induced in mice by implanting endometrium from donors and that developed into experimental endometriosis after 6 weeks. Mice were then randomly assigned to three groups (n = 12 per group). Group 1 received recombinant L-ICON3 treatment, whereas group 2 and 3 received PBS and an IgG isotype control, respectively, for an additional 6 weeks. Then mice were euthanized, and endometriotic lesions were collected and analyzed. Primary outcomes included lesion size and endometriosis wall thickness, and immunohistochemistry staining for immune markers. L-ICON3-treated mice demonstrated 2.5-fold decrease in lesion size and endometriosis wall thickness, as well as enhanced recruitment of T and NK cells into lesions, while also showing a significant decrease in TF expression compared to treatments with isotype control IgG or PBS. Our findings demonstrate the L-ICON3 is a promising novel therapeutic approach for the treatment of endometriosis that selectively binds TF and recruits T and NK immune cells into the lesions.","PeriodicalId":520678,"journal":{"name":"Journal of molecular medicine (Berlin, Germany)","volume":"104 1","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13521994/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148842729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0