Molecular and Cellular Biochemistry最新文献

{"title":"Does autophagy play a key role in the protective effect of oleic acid against oxidative stress in endothelial cells?","authors":"Ana García-Aguilar, Olga Palomino, Adrián González, Carlos Guillén, María S Fernández-Alfonso, Luis Goya","doi":"10.1007/s11010-025-05410-z","DOIUrl":"https://doi.org/10.1007/s11010-025-05410-z","url":null,"abstract":"<p><p>Endothelial dysfunction is a primary cause of cardiovascular complications that lead to atherosclerosis, while oxidative stress has been highligthted as one mechanism involved in endothelial dysfunction. Prevention of oxidative stress may then be a strategy to avoid endothelial dysfunction and cardiovascular disease. As the ability of oleic acid of reducing reactive oxygen species and related oxidative stress has been shown, other potential cellular mechanisms that could be responsible for the protective effect have to be evaluated. Autophagy is considered a cellular adaptive response under stressful conditions; thus, its role in the protective mechanism of oleic acid in stressed endothelial (EA.hy926) cells was assessed. To that end, cell viability and markers of oxidative status, such as reactive oxygen species, reduced glutathione, glutathione peroxidase, and reductase were evaluated. Moreover, the expression of several key autophagy-related proteins, such as microtubule-associated protein 1 light chain 3 beta and ubiquitin-binding protein p62/sequestosome 1, were investigated. The results showed that oleic acid within the micromolar range stimulated autophagy. However, when autophagy was inhibited in endothelial cells under oxidative stress, changes in the chemoprotective effect of oleic acid were minimal. These results suggest a limited contribution of autophagy to the protective effect of oleic acid under conditions of severe oxidative stress.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145301904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Silencing of telomerase RNA component induces autophagy and ferroptosis in A549 and H838 lung cancer cells via AMPK-mediated signaling.","authors":"Honglian Zhou, Xiaobi Huang, Xiaoyan Cheng, Zijian Liu, Hui Yu, Zhong Huang, Yongyang Chen, Hongyi Liu, Xiaohong Xu, Zhixiong Yang, Wenmei Su","doi":"10.1007/s11010-025-05337-5","DOIUrl":"https://doi.org/10.1007/s11010-025-05337-5","url":null,"abstract":"<p><p>Long non-coding RNAs (lncRNAs) are involved in tumorigenesis. The telomerase RNA component (TERC) is a lncRNA that functions as an essential template for the addition of the telomere repeats; its dysfunctions has been associated with various human diseases. However, how dysregulation of TERC expression and activity affects lung adenocarcinoma (LUAD) progression remains elusive. RNA sequencing (RNA-seq) analysis was used to compare the expression levels of TERC in cancerous and adjacent normal lung tissues. Functional assays of TERC in LUAD cell lines were performed by siRNA-mediated knockdown. Cell proliferation was assessed using the water-soluble tetrazolium salt-1 (WST-1) assay, while colony formation capability was evaluated through colony formation assays. Cell migration and invasion were analyzed using Transwell assays. Reactive oxygen species (ROS) levels were determined by flow cytometry and examined by fluorescence microscopy. The morphology of mitochondria was observed using transmission electron microscopy. Protein expression was analyzed by western blot. The formation of autophagosomes was monitored by fluorescence microscopy following the expression of fluorescently tagged LC3. Xenograft experiments were conducted to test the inhibition of TERC knockdown in LUAD proliferation in vivo. RNA-seq analysis showed that the expression of TERC was upregulated in lung cancer tissues. Silencing TERC suppressed the proliferation, migration, and invasion of lung cancer cells in vitro. Additionally, it inhibited the growth of pulmonary xenografts in mice in vivo. Mechanistic analyses indicated that silencing of TERC increased the expression of autophagy-related proteins LC3B, Beclin-1, and AMP-activated protein kinase (AMPK), while the expression of p62 protein and ferroptosis-regulated proteins GPX4 and SLC7A11 were diminished. Importantly, inhibition of AMPK function counterbalanced the effects of TERC knockdown on autophagy and ferroptosis in LUAD cells. These findings reveal that suppression of TERC in lung cancer promotes autophagy and ferroptosis via regulation of AMPK. They help to understand the mechanism underlying TERC activity in tumorigenesis. It will be of interest to determine the clinical significance of TERC dysregulation in lung cancer.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145286560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Crosstalk between tumor-associated macrophages and the B7/CD28 family in immune checkpoint inhibitor-induced immunotherapy.","authors":"Rui Bai, Wenjie Sun","doi":"10.1007/s11010-025-05405-w","DOIUrl":"https://doi.org/10.1007/s11010-025-05405-w","url":null,"abstract":"<p><p>The tumor microenvironment (TME) is a complex ecosystem containing various cells and secreted molecules that play critical roles in the progression of tumorigenesis. In recent years, antitumor strategies aimed at reshaping the TME have attracted much attention. Tumor-associated macrophages (TAMs) are the most abundant immune cells infiltrating the TME, contributing more than 50% of the tumor mass. In a variety of cancers, TAMs participate in the processes of tumor formation, migration, and invasion and are significantly related to a poor prognosis. Furthermore, TAMs play crucial roles in the regulation of the TME, chemoresistance, and immunotherapy resistance, and are potential targets in tumor therapy. TAMs are supposed to be carriers of ligands of immune checkpoint inhibitors (ICIs). Therefore, it is expected that TAMs can regulate T cell immune function through providing costimulatory/coinhibitory signals and may significantly influence the immune response related to ICIs. B7/CD28 family members are the best studied immune checkpoint receptors and ligands. Several studies have demonstrated that these B7/CD28 family members are highly expressed on TAMs, eliminating the inhibitory signal of T cell activation. However, the role of TAMs and B7/CD28 family members in ICI-induced immunotherapy is complicated and need to be illustrated. This study aims to review the crosstalk between TAMs and the B7/CD28 family, highlight the role of TAM-mediated tumor immune escape in ICI immunotherapy, explore the application prospects of TAMs in reversing ICI resistance.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145286568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigenetic modulation of CTCs as a novel therapeutic target in oncology.","authors":"Husni Farah, Munther Kadhim Abosaoda, Hayjaa Mohaisen Mousa, S Renuka Jyothi, Priya Priyadarshini Nayak, J Bethanney Janney, Gurjant Singh, Ashish Singh Chauhan","doi":"10.1007/s11010-025-05402-z","DOIUrl":"https://doi.org/10.1007/s11010-025-05402-z","url":null,"abstract":"<p><p>Tumor metastasis is the primary cause of high mortality rates among cancer patients. Invasive tumor cells disseminate through the bloodstream as circulating tumor cells (CTCs) and subsequently colonize secondary organs. In addition to genetic mutations that govern biological processes, epigenetic alterations also regulate tumor cell gene expression and chromosome stability. Dysregulation of these patterns is pivotal to carcinogenesis, tumor progression, and metastasis. This narrative review initiates with a comprehensive overview of the biology of CTCs and the processes that contribute to epithelial-mesenchymal transition (EMT), immune surveillance, and colonization. Subsequently, the impact of epigenetic modifications in CTCs on these metastatic processes during CTC migration, survival, and dissemination will be examined. In addition, the paper presents the implications of targeting epigenetics in CTCs for cancer patients and introduces CTCs as new biomarkers for early detection, prognosis, and targeted therapies to improve patient outcomes.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145274929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanism of maternal gestational diabetes mellitus exacerbating myocardial injury in male offspring by upregulating growth differentiation factor 15 to promote mitochondrial dysfunction.","authors":"Mingdong Zhu, Fengling Yin, Yanan Qiu, Yang Liu","doi":"10.1007/s11010-025-05395-9","DOIUrl":"https://doi.org/10.1007/s11010-025-05395-9","url":null,"abstract":"<p><p>Gestational diabetes mellitus (GDM) is a prevalent metabolic disturbance in pregnancy. This study analyzed the mechanism of maternal GDM inducing myocardial injury in male offspring through growth differentiation factor-15 (GDF-15). Pregnant rats were randomly assigned to the GDM-mother (streptozotocin [STZ] induction) and the Control-mother (normal saline injection) groups. Here, 32 male offspring from the Control-mother group and 92 from the GDM-mother group were used for experiments. The myocardial ischemia model was established by left anterior descending (LAD) coronary artery ligation in 6-week-old male offspring. Male offspring in the GDM-mother group were treated with sh-Gdf15, pyrroloquinoline quinone, or rotenone. Cardiac function, oxidative stress-associated indicators, myocardial infarct size and necrosis, inflammatory infiltration, cardiomyocyte apoptosis, mitochondrial damage, and Gdf15 mRNA and protein expression were examined using echocardiography, kits, TTC/H&E/TUNEL staining, flow cytometry, RT-qPCR, and western blot. GDM maternal rats had elevated blood glucose and a reduced body weight, representing successful modeling. Prenatal STZ exposure did not affect blood glucose but decreased the body weight in male offspring. The baseline cardiac function was not affected by prenatal STZ exposure, whereas LAD ligation-induced ischemia caused severe cardiac dysfunction in GDM male offspring versus controls. GDF-15 was upregulated in GDM rat male offspring, and its knockdown alleviated myocardial injury. Adult male offspring of GDM rats exhibited pronounced mitochondrial damage, and mitochondrial homeostasis restoration improved ischemia-caused cardiac dysfunction. Suppressing mitochondrial function partly abrogated cardioprotective effects of Gdf15 knockdown. Maternal GDM promoted myocardial injury in male offspring by upregulating GDF-15 to aggravate mitochondrial damage.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145274943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Yin and Yang of copper in cardiovascular health and disease.","authors":"Jiaoyu Li, Yang Li, Qianran Shen, Yan Zhang, Yi Yu, Xiaofang Li, Yuyan Xiong","doi":"10.1007/s11010-025-05401-0","DOIUrl":"https://doi.org/10.1007/s11010-025-05401-0","url":null,"abstract":"<p><p>Copper (Cu), an essential micronutrient and transition metal, plays a critical role in numerous biological processes, particularly within the cardiovascular system. Both cuprous (Cu⁺) and cupric (Cu²⁺) forms of copper are extensively involved in regulating key cellular biological processes, including apoptosis, autophagy, cell proliferation, mitochondrial dysfunction, inflammation, immune dysregulation, glucose/lipid metabolism and gut microbiota. Maintaining copper homeostasis is fundamental for cardiovascular health. Growing evidence indicates that copper dyshomeostasis may act as a critical trigger for the onset and progression of cardiovascular diseases (CVDs), such as atherosclerosis, stroke, hypertension, cardiac hypertrophy, heart failure, ischemia/reperfusion injury, and myocardial infarction. Accordingly, targeting copper dysregulation may offer a promising strategy for CVDs therapy. In this review, we summarize the essential functions of copper and examine how its dysregulation contributes to cellular dysfunction and the pathophysiology of CVDs. We further explore the molecular mechanisms by which copper imbalance drives CVD pathogenesis. Additionally, recent advances and current challenges in copper-targeted therapeutic strategies are discussed. By elucidating the Yin-Yang role of copper in cardiovascular biology, this review may provide a comprehensive foundation for future research and therapeutic development.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145275031","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retraction Note: Increase of autophagy and attenuation of apoptosis by Salvigenin promote survival of SH-SY5Y cells following treatment with H₂O₂.","authors":"Ghazaleh Rafatian, Fariba Khodagholi, Mahdi Moridi Farimani, Shahnaz Babaei Abraki, Mossa Gardaneh","doi":"10.1007/s11010-025-05404-x","DOIUrl":"https://doi.org/10.1007/s11010-025-05404-x","url":null,"abstract":"","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145251864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A diagnostic model of atherosclerosis based on the oxidative stress-glycolysis co-regulatory network.","authors":"Weiqing Han, Xiang Long, Shuqiang Zhu, Mingchun You, Jianjun Xu","doi":"10.1007/s11010-025-05396-8","DOIUrl":"https://doi.org/10.1007/s11010-025-05396-8","url":null,"abstract":"<p><p>Atherosclerosis (AS) is a major cardiovascular disorder, with challenges in early diagnosis and a lack of individualized treatment that require urgent attention. This study employed bioinformatics approaches to identify critical genetic markers linked to AS pathogenesis and explored their underlying molecular mechanisms to facilitate advancements in diagnostic accuracy and therapeutic interventions. We successfully identified genes exhibiting significant differential expression in AS, i.e., oxidative stress and glycolysis-related differentially expressed genes (OSGRDEGs). Through weighted gene co-expression network analysis, three modules (MEturquoise, MEred, and MEgreen) significantly associated with AS were screened, and 72 module genes were found to be identical to OSGRDEGs. A protein-protein interaction network was designed through comprehensive integration of data from the STRING database, followed by visualization and topological analysis employing Cytoscape software. Candidate genes were further evaluated using five distinct algorithms within the CytoHubba plugin, resulting in 12 high-confidence hub genes associated with AS pathogenesis. The 12 hub genes screened by machine algorithm were further screened by modeling to obtain 7 key genes. Finally, statistical analysis revealed marked variations in the infiltration levels of eight immune cell populations across the comparative groups. Monocytes and M0 macrophages showed significant negative correlations in subtypes A and B. Notably, APOE and CXCL1 demonstrated strong positive associations with M0 macrophages and monocytes, respectively, as evidenced by our correlation analysis. This study highlights the use of a bioinformatics approach to identify molecular markers of AS, with future work focused on validating their potential clinical applications.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145232976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unraveling the interplay between RAS axes and NOX signaling in fibroblasts during cardiac fibrosis.","authors":"Gauri Chaturvedi, Anita Chauhan, Nandini Dubey, Sandeep Seth, Jagriti Bhatia, Subhash Chandra Yadav, Harlokesh Narayan Yadav","doi":"10.1007/s11010-025-05400-1","DOIUrl":"https://doi.org/10.1007/s11010-025-05400-1","url":null,"abstract":"<p><p>Cardiac fibrosis results from cardiovascular diseases (CVDs) and is characterized by excessive extracellular matrix (ECM) accumulation, particularly collagen, leading to cardiac dysfunction. Despite the availability of treatments for CVDs, no targeted therapies are available to prevent disease progression to irreversible stages. Further research is needed to explore the pathways and signaling molecules involved in this progression. The renin-angiotensin system (RAS) plays a significant role, with pharmacological agents targeting its harmful axis, i.e., Angiotensin-converting enzyme (ACE)/Angiotensin II (Ang II)/Angiotensin 1 receptor (AT1R) axis, while an antagonistic axis, ACE2/Angiotensin 1-7 (Ang 1-7)/mitochondrial assembly receptor (MasR) axis offers cardioprotective effects. Reactive oxygen species (ROS) also contribute to CVDs, with NADPH oxidases (NOXes) being key inducers of ROS. NOX1, NOX2, NOX4, and NOX5 are upregulated in pathological conditions, exacerbating the disease. This review focuses on the mechanisms by which the ACE/Ang II/AT1R and ACE2/Ang 1-7/MasR axes regulate NOX activity, aiming to enhance our understanding of future targeted therapies.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145225718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TAP1 promotes immune escape by activating JNK/STAT1/PD-L1 signaling in EBV-associated gastric cancer.","authors":"Wenqing Shan, Guoqingyuan Li, Hailing Zhang, Ranran Zhang, Jialong Liu, Liping Gao, Yizhang Li, Lilan Fan, Chaoran Yang, Jing Liu","doi":"10.1007/s11010-025-05319-7","DOIUrl":"10.1007/s11010-025-05319-7","url":null,"abstract":"<p><p>Epstein-Barr virus (EBV) infection accounts for approximately 10% of gastric cancer (GC) cases and is strongly linked to immune evasion, although the precise mechanisms remain unclear. Transporter associated with antigen processing 1 (TAP1), a member of ATP-binding cassette subfamily B, is overexpressed in EBV-associated gastric cancer (EBVaGC) and is implicated in tumor immune evasion. TAP1 expression levels in EBV-positive and EBV-negative gastric cancer samples were analyzed using TCGA and GEO datasets. Molecular biology techniques were used to investigate the regulatory pathways involved in TAP1. The role of TAP1 in modulating immunotherapy responses was validated using T-cell cytotoxicity assays and mouse models. TAP1 was significantly overexpressed in EBV-positive gastric cancer tissues and cell lines. Mechanistic studies revealed that EBV latent membrane protein 2A (LMP2A) activates the NF-κB P65 pathway, which directly binds to the TAP1 promoter and enhances transcription. Furthermore, TAP1 expression was positively correlated with PD-L1 levels. In immunocompetent mice, shTAP1 MFC cells exhibited significantly reduced growth relative to that in immunodeficient mice. TAP1 upregulates PD-L1 via the JNK/STAT1 pathway, thereby influencing tumor immunotherapy responses. Notably, TAP1 silencing combined with PD-1 monoclonal antibody treatment significantly inhibited gastric cancer cell proliferation. This study revealed a mechanism through which the EBV protein LMP2A drives TAP1 expression via NF-κB signaling. TAP1, in turn, regulates PD-L1 expression via the JNK/STAT1 pathway, contributing to immune evasion. These findings highlight TAP1 as a promising therapeutic target for improving the efficacy of immunotherapy in gastric cancer.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"5429-5446"},"PeriodicalIF":3.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144275394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}