Cellular and Molecular Life Sciences最新文献

{"title":"Inflammatory metabolite 7α,25-OHC promotes TIMP1 expression in COVID-19 monocytes through synergy effect of SMARCC1/JUND/H3K27ac.","authors":"Ying Feng, Zheng Wu, Kefan Hu, Shenzhen Yuan, Jun Li, Yi Wang, Zhongyi Wang, Han Yang, Zhi-Hui Luo, Jingjiao Zhou","doi":"10.1007/s00018-025-05721-w","DOIUrl":"10.1007/s00018-025-05721-w","url":null,"abstract":"<p><p>Chromatin remodeling factors are involved in the inflammatory responses, contributing to tissue damage and multi-organ dysfunction in COVID-19 patients. However, the underlying mechanisms remain unclear. In this study, high-dimensional analyses of single-cell RNA sequencing and single-cell ATAC sequencing data revealed increased chromatin accessibility at the promoters or enhancers of the pro-inflammatory cytokine tissue inhibitor of metalloproteinase-1 (TIMP1), as well as altered gene transcription profiles in monocytes from COVID-19 patients. Motif enrichment and positive regulators analyses identified SMARCC1, the core subunit of the chromatin remodeling complex, and the transcription factor JUND as positive regulators to co-modulate TIMP1 expression. In-vitro experiments, co-immunoprecipitation and chromatin immunoprecipitation (ChIP)-qPCR, and others, demonstrated the collaboration of SMARCC1 and JUND. Increased 7α,25-dihydroxycholesterol (7α,25-OHC) enhanced SMARCC1-JUND interactions to co-regulate TIMP1 expression. Further investigation indicated that 7α,25-OHC promoted the expression of SMARCC1 and its co-localization with H3K27ac, which involved in the expression of TIMP1 and inflammatory responses. Our study highlights the critical roles of SMARCC1 and JUND in COVID-19 inflammation, and offers the potential targets for the prevention and treatment of COVID-19.</p>","PeriodicalId":10007,"journal":{"name":"Cellular and Molecular Life Sciences","volume":"82 1","pages":"208"},"PeriodicalIF":6.2,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12095718/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144119064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic changes in neuroendocrine neoplasms.","authors":"Chunhua Hu, Lingyi Chen, Yi Ding, Mujie Ye, Qiyun Tang","doi":"10.1007/s00018-025-05656-2","DOIUrl":"10.1007/s00018-025-05656-2","url":null,"abstract":"<p><p>Neuroendocrine neoplasms (NENs) are a group of highly heterogeneous neoplasms originating from neuroendocrine cells with a gradually increased incidence. Metabolic change is one of the recognized markers of tumor progression, which has been extensively and systematically studied in other malignant tumors. However, metabolic change in NENs has been relatively poorly studied, and systematic reviews are lacking. We reviewed the relationship between metabolic changes and NENs from the aspects of glucose metabolism, lipid metabolism, metabolic syndrome, amino acid metabolism and metabolomics, and discussed the potential therapeutic strategies of metabolic changes for NENs.</p>","PeriodicalId":10007,"journal":{"name":"Cellular and Molecular Life Sciences","volume":"82 1","pages":"205"},"PeriodicalIF":6.2,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12084448/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Downregulation of CMIP contributes to preeclampsia development by impairing trophoblast function via the PDE7B-cAMP pathway.","authors":"Yina Li, Xinjing Yan, Haiyang Yu, Yuanbo Zhou, Yongrui Gao, Xinyuan Zhou, Yujie Yuan, Yangnan Ding, Qianqian Shi, Yang Fang, Hongmei Du, Enwu Yuan, Xin Zhao, Linlin Zhang","doi":"10.1007/s00018-025-05726-5","DOIUrl":"10.1007/s00018-025-05726-5","url":null,"abstract":"<p><strong>Background: </strong>Preeclampsia (PE) is one of the leading causes of perinatal maternal and fetal morbidity and mortality, but its precise mechanism remains elusive. Previous research has suggested that c-Maf-inducible protein (CMIP) is abnormally expressed in PE pathophysiology. Therefore, we aimed to explore the potential role of CMIP and its downstream molecules in PE.</p><p><strong>Methods: </strong>Multiplex immunofluorescence and immunohistochemical assays were conducted on preeclamptic placentas. Functional analysis of CMIP was performed in HTR-8/SVneo cells through transfection experiments in which either CMIP was overexpressed or downregulated. RNA sequencing was utilized to identify the molecular pathways downstream of CMIP. The impact of hypoxia on CMIP levels was assessed in three different types of trophoblast cells. The therapeutic efficacy of CMIP was evaluated in an N(ω)-nitro-L-arginine methyl ester (L-NAME)-induced rat model of PE.</p><p><strong>Results: </strong>CMIP expression was downregulated in extrachorionic trophoblasts (EVTs) and syncytiotrophoblasts (STBs) in preeclamptic placentas. This downregulation of CMIP in trophoblast cells disrupts cell proliferation, migration, invasion, and angiogenesis by upregulating the PDE7B-cAMP pathway, while elevated CMIP levels enhance these cellular functions. Hypoxia reduced CMIP expression in all three types of trophoblast cells. Moreover, in a rat model of PE, supplementation with CMIP alleviated hypertension and increased fetal weight and number.</p><p><strong>Conclusions: </strong>Our study demonstrates for the first time that the CMIP-PDE7B-cAMP pathway contributes to PE development by influencing trophoblast function. The signaling pathway proteins involved in PE induced by CMIP may provide new clues to the occurrence of PE and new targets for future PE therapy.</p>","PeriodicalId":10007,"journal":{"name":"Cellular and Molecular Life Sciences","volume":"82 1","pages":"203"},"PeriodicalIF":6.2,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12081820/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GPI-anchorless prion disease is sensitive to oxidative stress and shows potential for treatment with edaravone, based on iPS-derived neuron study.","authors":"Kosuke Matsuzono, Hiroyuki Honda, Takafumi Mashiko, Reiji Koide, Eiji Sakashita, Hitoshi Endo, Tetsuyuki Kitamoto, Shigeru Fujimoto","doi":"10.1007/s00018-025-05698-6","DOIUrl":"10.1007/s00018-025-05698-6","url":null,"abstract":"<p><p>Only a few reports have generated induced pluripotent stem cells from patients with prion diseases, making it important to conduct translational studies using cells derived from individuals with prion protein (PRNP) mutations. In this study, we established induced pluripotent stem cells from a patient with a glycosylphosphatidylinositol-anchorless PRNP mutation (Y162X), which leads to abnormal deposits of prion protein in various organs. While no abnormal intracellular prion protein deposits were observed in the neurons differentiated from PRNP Y162X induced pluripotent stem cells, extracellular PrP aggregates secretions were significantly increased, and these cells were significantly more sensitive to oxidative stress compared to control cells. Utilizing this PRNP Y162X iPSC-derived neuron model, we discovered that edaravone reduced the sensitivity of PRNP Y162X cells to oxidative stress. Following this finding, we treated a PRNP Y162X patient with edaravone for two years, which successfully suppressed indicators of disease progression. Our study demonstrates that the pathology of the glycosylphosphatidylinositol-anchorless PRNP mutation is associated with oxidative stress and highlights the potential of induced pluripotent stem cell technology in identifying novel treatments for rare prion diseases.</p>","PeriodicalId":10007,"journal":{"name":"Cellular and Molecular Life Sciences","volume":"82 1","pages":"202"},"PeriodicalIF":6.2,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12081781/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Taurolidine inhibits influenza virus infection and prevents influenza-induced cytokine storm, vasoconstriction and lung damage.","authors":"Chaoxiang Lv, Jin Guo, Rongbo Luo, Yuanguo Li, Bingshuo Qian, Xiaopan Zou, Tiecheng Wang, Beilei Shen, Weiyang Sun, Yuwei Gao","doi":"10.1007/s00018-025-05636-6","DOIUrl":"https://doi.org/10.1007/s00018-025-05636-6","url":null,"abstract":"<p><p>Influenza virus causes worldwide outbreaks and seasonal epidemics, posing a severe threat to public health and social development. Effective prevention and treatment of influenza infections remain major challenge for global healthcare. In this study, we observed that taurolidine effectively inhibited the proliferation of several human or animal influenza virus strains and protected mice from lethal-infection. Taurolidine treatment decreased the viral titer in the lungs of infected mice, reduced the ratio of immune cells, and alleviated lung pathology. Additionally, taurolidine treatment attenuated the rise of blood pressure, pulse wave velocity, and pulmonary aortic thickness in a mouse model for influenza virus infection. We also found that taurolidine significantly decreased intracellular Ca²⁺ concentration and effectively alleviated pulmonary artery vasoconstriction during influenza virus infection. Mechanistically, we observed that vascular smooth muscle contraction signaling pathway was significantly enriched, and taurolidine inhibited the activation of the MLCK/p-MLC pathway. Taking together, these findings confirm the effectiveness of taurolidine as an antiviral agent and highlight its important roles in mitigating host immune cell infiltration and vasoconstriction induced by influenza virus infection.</p>","PeriodicalId":10007,"journal":{"name":"Cellular and Molecular Life Sciences","volume":"82 1","pages":"201"},"PeriodicalIF":6.2,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12078922/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"miR-126-5p protects from URSA via inhibiting Caspase-1-dependent pyroptosis of trophoblast cells.","authors":"Xiaoxiao Zhu, Ke Xu, Shuang Ai, Yingjie Zhang, Chu Chu, Ran Wei, Shufeng Gao, Lu Liu, Wei Li, Yunhong Zhang, Siambi Kikete, Xinkui Liu, Zhen Zhang, Xia Li","doi":"10.1007/s00018-025-05713-w","DOIUrl":"10.1007/s00018-025-05713-w","url":null,"abstract":"<p><p>Unexplained recurrent spontaneous abortion (URSA) is a distressing pregnancy complication that seriously threat to women's reproductive health. Trophoblast pyroptosis was involved in the occurrence of URSA, but the potential mechanism remains unclear. In this work, we found CASP1 transcription and the level of pyroptosis were significantly elevated in the villous tissues of URSA patients. Suppression of cell pyroptosis by Gasdermin-D (GSDMD) or Caspase-1 inhibitors can reduce embryo resorption rate of URSA mice, while Caspase-1 over-expression in normal pregnant (NP) mice can aggravate embryo resorption. Meanwhile, a pronounced decline in the expression of microRNA-126-5p (miR-126-5p) was found in URSA patients, which was inversely related to CASP1 expression. Over-expression of miR-126-5p restrained trophoblast pyroptosis via inhibiting Caspase-1/GSDMD signaling pathway by direct binding to 3'-UTR of CASP1. Moreover, experiments in vivo substantiated that up-regulation of miR-126-5p effectively suppressed Caspase-1-mediated pyroptosis in placental tissue and significantly reduced embryo resorption rate. Collectively, these results underscored that diminished miR-126-5p expression plays a crucial role in URSA by enhancing trophoblast pyroptosis through activating Caspase-1/GSDMD signaling pathway. As a result, miR-126-5p shows significant promise as a possible biomarker for diagnosis and treatment of URSA.</p>","PeriodicalId":10007,"journal":{"name":"Cellular and Molecular Life Sciences","volume":"82 1","pages":"204"},"PeriodicalIF":6.2,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12081782/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"USP1 inhibits influenza A and B virus replication in MDCK cells by mediating RIG-I deubiquitination.","authors":"Yuejiao Liao, Siya Wang, Tian Tang, Chengfang Li, Chenhao Yang, Liyuan Ma, Jin Ye, Jiamin Wang, Di Yang, Zilin Qiao, Zhongren Ma, Zhenbin Liu","doi":"10.1007/s00018-025-05733-6","DOIUrl":"10.1007/s00018-025-05733-6","url":null,"abstract":"<p><p>The post-translational modification and stability regulation of RIG-I play critical roles in promoting IFN-I production and maintaining immune homeostasis. In this study, we found that ubiquitin-specific peptidase 1 (USP1) promotes RIG-I protein stability through deubiquitination, which in turn enhances antiviral immunity through the production of inflammatory cytokines, and inhibits the replication of influenza virus in MDCK cells. In contrast, USP1 knockdown inhibited the deubiquitination of RIG-I, decreased the RIG-I protein level, and significantly increased the influenza virus titer. Meanwhile, inhibition of USP1 expression did not have a significant effect on the proliferation of MDCK cells, suggesting that USP1 could be used as a target gene to establish a vaccine-producing MDCK cell line. The above results provide a more comprehensive understanding of the function of USP1 and the antiviral response mechanism, and provide a theoretical and methodological basis for the screening of target genes for the artificial establishment of high-yield MDCK cell lines for vaccine production.</p>","PeriodicalId":10007,"journal":{"name":"Cellular and Molecular Life Sciences","volume":"82 1","pages":"200"},"PeriodicalIF":6.2,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12078747/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aging and chronic inflammation: impacts on olfactory dysfunction-a comprehensive review.","authors":"Yingqi Xie, Shenglei Wang, Xudong Cha, Fengzhen Li, Zengyi Xu, Jian Wu, Huanhai Liu, Wenwen Ren","doi":"10.1007/s00018-025-05637-5","DOIUrl":"10.1007/s00018-025-05637-5","url":null,"abstract":"<p><p>Olfactory dysfunction (OD) is a common nasal disease, particularly prevalent among the elderly population, significantly impacting the affected individuals' quality of life. This review focuses on the influence of aging and chronic inflammation on olfactory dysfunction, presenting insights from both the peripheral and central olfactory systems. By exploring the molecular mechanisms and pathological changes underlying the occurrence of olfactory dysfunction in relation to age-related diseases and chronic inflammation conditions, we aim to provide a comprehensive theoretical foundation for further research and offer valuable insights for more effective treatment of olfactory dysfunction.</p>","PeriodicalId":10007,"journal":{"name":"Cellular and Molecular Life Sciences","volume":"82 1","pages":"199"},"PeriodicalIF":6.2,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12069206/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143986603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decoding microRNA arm switching: a key to evolutionary innovation and gene regulation.","authors":"Danillo Pinhal, Leandro de B Gonçalves, Vinícius F Campos, James G Patton","doi":"10.1007/s00018-025-05663-3","DOIUrl":"https://doi.org/10.1007/s00018-025-05663-3","url":null,"abstract":"<p><p>miRNA arm switching is a pivotal regulatory mechanism that allows organisms to fine-tune gene expression by selectively utilizing either the 5p or 3p strand of a miRNA duplex. This process, conserved across species, facilitates adaptive responses to developmental cues, environmental changes, and disease states. By dynamically altering strand selection, arm switching reshapes gene regulatory networks, contributing to phenotypic diversity and evolutionary innovation. Despite its growing recognition, the mechanisms driving arm switching-such as thermodynamic properties and enzyme-mediated processing-remain incompletely understood. This review synthesizes current findings, highlighting arm switching as a highly conserved mechanism with profound implications for the evolution of regulatory networks. We explore how this phenomenon expands miRNA functionality, drives phenotypic plasticity, and co-evolves with miRNA gene duplications to fuel the diversification of biological functions across taxa.</p>","PeriodicalId":10007,"journal":{"name":"Cellular and Molecular Life Sciences","volume":"82 1","pages":"197"},"PeriodicalIF":6.2,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12065703/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143992973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of intraflagellar transport protein IFT140 in the formation and function of motile cilia in mammals.","authors":"Yi Tian Yap, Jiehong Pan, Jian Xu, Shuo Yuan, Changmin Niu, Cheng Zheng, Wei Li, Ting Zhou, Tao Li, Yong Zhang, Michael J Holtzman, Gregory J Pazour, Rex A Hess, Christopher V Kelly, Aminata Touré, Steven L Brody, Zhibing Zhang","doi":"10.1007/s00018-025-05710-z","DOIUrl":"https://doi.org/10.1007/s00018-025-05710-z","url":null,"abstract":"<p><p>Cilia are microtubular structures extending from the surface of most mammalian cells. They can be categorized as motile cilia and primary sensory cilia. Both types possess intraflagellar transport (IFT) machinery, composed of unique protein complexes that travel along the microtubules to deliver proteins for ciliary and flagellar assembly, disassembly, and homeostasis. Although the role of IFT in primary cilia formation has been well studied, little is known about its role in mammalian motile cilia assembly. We generated conditional knockout mice by breeding floxed Ift140 mice with the FOXJ1-Cre transgenic mouse line to specifically delete Ift140 from cells that assemble motile cilia. Mice with Ift140 deficiency did not have laterality defects or gross; however most died prior to sexual maturity. Those mutants that survived to adulthood were completely infertile. Males demonstrated abnormal spermatogenesis associated with reduced sperm count and motility, together with short length flagella, and abnormal morphology. Cilia length was diminished in the epithelial cells of the efferent ductules and airways. Cilia from cultured tracheal epithelial cells were also short and had reduced beat frequency (CBF). Ultrastructural studies revealed the presence of inner and outer dynein arms, but an abnormal central apparatus, and the accumulation of particles within the cilia. Overall, the short length and abnormal localization of ciliary proteins in Ift140 conditional mutants resulted in inadequate cilia function despite proper localization of the dynein motor complexes. We propose a key role of Ift140 for motile cilia assembly in certain tissues and suggest that genetic alterations of IFT140 could be associated with motile ciliopathies.</p>","PeriodicalId":10007,"journal":{"name":"Cellular and Molecular Life Sciences","volume":"82 1","pages":"198"},"PeriodicalIF":6.2,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12065702/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143968760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}