Molecular and Cellular Biochemistry最新文献

{"title":"Editorial Expression of Concern: Estrogen receptor, calcium mobilization and rat sperm motility.","authors":"G Sethi Saberwal,M K Sharma,N Balasinor,J Choudhary,H S Juneja","doi":"10.1007/s11010-024-05114-w","DOIUrl":"https://doi.org/10.1007/s11010-024-05114-w","url":null,"abstract":"","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142265012","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 METTL3/TRAP1 axis as a key regulator of 5-fluorouracil chemosensitivity in colorectal cancer","authors":"Qingjie Kang, Xiaoyu Hu, Zhenzhou Chen, Xiaolong Liang, Song Xiang, Ziwei Wang","doi":"10.1007/s11010-024-05116-8","DOIUrl":"https://doi.org/10.1007/s11010-024-05116-8","url":null,"abstract":"<p>Colorectal cancer (CRC) remains a significant clinical challenge, with 5-Fluorouracil (5-FU) being the frontline chemotherapy. However, chemoresistance remains a major obstacle to effective treatment. METTL3, a key methyltransferase involved in RNA methylation processes, has been implicated in CRC carcinogenesis. However, its role in modulating CRC sensitivity to 5-FU remains elusive. In this study, we aimed to investigate the role and mechanisms of METTL3 in regulating 5-FU chemosensitivity in CRC cells. Initially, we observed that 5-FU treatment inhibited cell viability and induced apoptosis, accompanied by a reduction in METTL3 expression in HCT-116 and HCT-8 cells. Subsequent assays including drug sensitivity, EdU, colony formation, TUNEL staining, and flow cytometry revealed that METTL3 depletion enhanced 5-FU sensitivity and increased apoptosis induction both in vitro and in vivo. Conversely, METTL3 overexpression conferred resistance to 5-FU in both cell lines. Moreover, knockdown of METTL3 in 5-FU-resistant CRC cell lines HCT-116/FU and HCT-15/FU significantly decreased 5-FU tolerance and induced apoptosis upon 5-FU treatment. Mechanistically, we found that METTL3 regulated 5-FU sensitivity and apoptosis induction by modulating TRAP1 expression. Further investigations using m6A colorimetric ELISA, dot blot, MeRIP-qPCR and RNA stability assays demonstrated that METTL3 regulated TRAP1 mRNA stability in an m6A-dependent manner. Additionally, overexpression of TRAP1 mitigated the cytotoxic effects of 5-FU on CRC cells. In summary, our study uncovers the pivotal role of the METTL3/TRAP1 axis in modulating 5-FU chemosensitivity in CRC. These findings provide new insights into the mechanisms underlying CRC resistance to 5-FU and may offer potential targets for future therapeutic interventions.</p><h3 data-test=\"abstract-sub-heading\">Graphical abstract</h3><p>Proposed working model of METTL3 regulating 5-FU sensitivity and apoptosis induction in CRC cells. METTL3 is frequently upregulated in CRC cells and is mainly localized in the nucleus of tumor cells [41]. In this study, we observed that down-regulating METTL3 levels led to a decrease in m6A modification on TRAP1 mRNA in both HCT-116 and HCT-8 cells. This reduction in m6A modification resulted in decreased stability of TRAP1 mRNA, ultimately facilitating 5-FU-induced apoptosis and heightening sensitivity to the drug. Our findings suggest a potential mechanism wherein elevated METTL3 expression in CRC cells may regulate TRAP1 expression in an m6A-dependent manner, thereby enabling cells to evade 5-FU-induced apoptosis and contribute to resistance against 5-FU chemotherapy.\u0000</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142264941","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":"Navigating heme pathways: the breach of heme oxygenase and hemin in breast cancer","authors":"Valeria Consoli, Valeria Sorrenti, Maria Gulisano, Mariarita Spampinato, Luca Vanella","doi":"10.1007/s11010-024-05119-5","DOIUrl":"https://doi.org/10.1007/s11010-024-05119-5","url":null,"abstract":"<p>Breast cancer remains a significant global health challenge, with diverse subtypes and complex molecular mechanisms underlying its development and progression. This review comprehensively examines recent advances in breast cancer research, with a focus on classification, molecular pathways, and the role of heme oxygenases (HO), heme metabolism implications, and therapeutic innovations. The classification of breast cancer subtypes based on molecular profiling has significantly improved diagnosis and treatment strategies, allowing for tailored approaches to patient care. Molecular studies have elucidated key signaling pathways and biomarkers implicated in breast cancer pathogenesis, shedding light on potential targets for therapeutic intervention. Notably, emerging evidence suggests a critical role for heme oxygenases, particularly HO-1, in breast cancer progression and therapeutic resistance, highlighting the importance of understanding heme metabolism in cancer biology. Furthermore, this review highlights recent advances in breast cancer therapy, including targeted therapies, immunotherapy, and novel drug delivery systems. Understanding the complex interplay between breast cancer subtypes, molecular pathways, and innovative therapeutic approaches is essential for improving patient outcomes and developing more effective treatment strategies in the fight against breast cancer.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142264940","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":"Helicobacter pylori induces GBA1 demethylation to inhibit ferroptosis in gastric cancer","authors":"Chenjie Shen, Huan Liu, Yuhan Chen, Mengpei Liu, Qian Wang, Jiaqi Liu, Jingjing Liu","doi":"10.1007/s11010-024-05105-x","DOIUrl":"https://doi.org/10.1007/s11010-024-05105-x","url":null,"abstract":"<p>This research investigates potential therapeutic targets for gastric cancer, focusing on ferroptosis-related genes. Gastric cancer is known for its lower survival rates, necessitating new treatment strategies. This study employed Mendelian randomization to identify ferroptosis-related genes and methylation sites in gastric cancer, examining correlations between Helicobacter pylori infection, <i>GBA1</i> gene expression, and promoter methylation with single-cell datasets and the TCGA-STAD database. We used <i>Helicobacter pylori</i>-infected gastric cancer cell models and used next-generation sequencing to monitor methylation changes pre- and post-infection. <i>GBA1</i> expression levels were assessed via qRT-PCR and Western blot both before and after infection. The effect of <i>Helicobacter pylori</i> on GC cell proliferation was analyzed using CCK-8 and EdU assays after knocking down the <i>GBA1</i> gene. The association between <i>Helicobacter pylori</i> infection and ferroptosis, including its reversibility after <i>GBA1</i> knockdown, was evaluated using FerrOrange, GSH, MDA, and C11-BODIPY assays. Mass spectrometry measured the impact of Helicobacter pylori and <i>GBA1</i> knockdown on lipid metabolism. An in vivo subcutaneous tumor-bearing model was also established to confirm these findings. Mendelian randomization analysis revealed that high <i>GBA1</i> expression and reduced methylation levels of its promoter are risk factors for gastric cancer. Single-cell sequencing and TCGA-STAD datasets indicated a positive correlation between <i>Helicobacter pylori</i> infection and <i>GBA1</i> expression, with a concurrent negative correlation between <i>GBA1</i> promoter methylation and <i>GBA1</i> expression. In gastric cancer cell lines, <i>Helicobacter pylori</i> infection was observed to enhance <i>GBA1</i> expression and decrease methylation levels at its promoter. Additionally, <i>Helicobacter pylori</i> promoted GC cell proliferation, an effect mitigated by knocking down <i>GBA1</i>. Infection also reduced lipid peroxidation, increased glutathione levels, and impeded ferroptosis in GC cells; however, these effects were reversed following <i>GBA1</i> knockdown. Changes in sphingolipid metabolism induced by I were detected in GC cell lines. In vivo experiments using a subcutaneous tumor-bearing model demonstrated that <i>Helicobacter pylori</i> infection fosters tumorigenesis in GC cells. Our study demonstrates that <i>Helicobacter pylori</i> infection triggers demethylation and upregulation of <i>GBA1</i>, subsequently inhibiting ferroptosis in gastric cancer cells. These findings suggest that targeting the <i>GBA1</i> pathway may offer a novel therapeutic approach for managing gastric cancer.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142264938","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":"Synergistic potential of stem cells and microfluidics in regenerative medicine","authors":"Resmi Rajalekshmi, Devendra K. Agrawal","doi":"10.1007/s11010-024-05108-8","DOIUrl":"https://doi.org/10.1007/s11010-024-05108-8","url":null,"abstract":"<p>Regenerative medicine has immense potential to revolutionize healthcare by using regenerative capabilities of stem cells. Microfluidics, a cutting-edge technology, offers precise control over cellular microenvironments. The integration of these two fields provides a deep understanding of stem cell behavior and enables the development of advanced therapeutic strategies. This critical review explores the use of microfluidic systems to culture and differentiate stem cells with precision. We examined the use of microfluidic platforms for controlled nutrient supply, mechanical stimuli, and real-time monitoring, providing an unprecedented level of detail in studying cellular responses. The convergence of stem cells and microfluidics holds immense promise for tissue repair, regeneration, and personalized medicine. It offers a unique opportunity to revolutionize the approach to regenerative medicine, facilitating the development of advanced therapeutic strategies and enhancing healthcare outcomes.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142265009","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":"Mechanisms of ferroptosis and glucagon-like peptide-1 receptor agonist in post-percutaneous coronary intervention restenosis","authors":"Miao Wang, Liren Wang, Huanxin Sun, Hong Yuan, Yonghong Li","doi":"10.1007/s11010-024-05118-6","DOIUrl":"https://doi.org/10.1007/s11010-024-05118-6","url":null,"abstract":"<p>Cardiovascular disease (CVD) claims millions of lives every year, with atherosclerotic cardiovascular disease (ASCVD) being the main cause. ASCVD treatment includes drug therapy, lifestyle intervention, and Percutaneous Coronary Intervention (PCI) all of which significantly enhance cardiovascular function and reduce mortality. However, hyperplasia can lead to vascular obstruction, worsen angina symptoms, or even cause heart disease, affecting patients' long-term prognosis. Therefore, finding effective ways to combat hyperplasia is crucial for cardiovascular therapy. In recent years, ferroptosis has gained attention as a new form of cell death closely associated with several diseases, including cardiovascular diseases. It involves complex metabolic processes critical for cellular homeostasis and normal function. Abnormal proliferation and phenotypic transformation of vascular smooth muscle cells (VSMC) are crucial mechanisms underlying cardiovascular disease development. Inhibiting ferroptosis in VSMC has the potential to significantly reduce neointima proliferation. Glucagon-like peptide-1 receptor agonist (GLP-1RA) constitutes a widely employed class of hypoglycemic agents with direct implications for the cardiovascular system, mitigating adverse cardiovascular events. Research indicates that the stimulation of GLP-1 holds promise as a therapeutic strategy in mitigating cardiovascular events such as restenosis. Hence, investigating the potential of GLP-1RA as a treatment option for cardiovascular ailments carries immense clinical significance.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142264939","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":"Knockdown of the Clock gene in the liver aggravates MASLD in mice via inhibiting lipophagy","authors":"Shuhong Yang, Xinxin Ren, Jia Liu, Yan Lei, Minqian Li, Fang Wang, Shuting Cheng, Junjie Ying, Jie Ding, Xiaohui Chen","doi":"10.1007/s11010-024-05109-7","DOIUrl":"https://doi.org/10.1007/s11010-024-05109-7","url":null,"abstract":"<p>The increased global prevalence of metabolic dysfunction-associated steatohepatitis (MASLD) has been closely associated with chronic disorders of the circadian clock. Herein, we investigate the role of <i>Clock</i>, a core circadian gene, in the pathogenesis of MASLD. Wild-type (WT) and liver-specific <i>Clock</i> knockdown (<i>Clock</i>-KD) mice were fed a Western diet for 20 weeks to induce MASLD. A cellular MASLD model was established by treating AML12 cells with free fatty acids and the effects of <i>Clock</i> knockdown were examined following transfection with <i>Clock</i> siRNA. Increased lipid deposition and more severe steatohepatitis and fibrosis were observed in the livers of Western diet-fed but not normal chow diet-fed <i>Clock</i>-KD mice after 20 weeks compared to WT mice. Moreover, the <i>Clock</i> gene was found to be significantly downregulated in WT MASLD mice. The <i>Clock</i> gene was shown to regulate the expression of lipophagy-related proteins (LC3B, P62, RAB7, and PLIN2) in vivo and in vitro. Knockdown of <i>Clock</i> was found to inhibit lipophagy resulting in increased accumulation of lipid droplets in the mouse liver and AML12 cells. Interestingly, the CLOCK protein was shown to interact with P62. However, knockdown of the <i>Clock</i> gene did not promote transcription of the <i>P62</i> gene but suppressed degradation of the P62 protein during lipophagy in AML12 cells. The hepatic <i>Clock</i> gene regulates lipophagy and affects lipid droplet deposition in liver cells, and thus plays a critical role in the development of MASLD induced by a Western diet.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142264943","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":"SIRT1 in acute lung injury: unraveling its pleiotropic functions and therapeutic development prospects","authors":"Yina Chen, Shuangyan Peng, Junjie Liang, Ke Wei","doi":"10.1007/s11010-024-05111-z","DOIUrl":"https://doi.org/10.1007/s11010-024-05111-z","url":null,"abstract":"<p>Acute lung injury (ALI) is a continuum of lung changes caused by multiple lung injuries, often associated with severe complications and even death. In ALI, macrophages, alveolar epithelial cells and vascular endothelial cells in the lung are damaged to varying degrees and their function is impaired. Research in recent years has focused on the use of SIRT1 for the treatment of ALI. In this paper, we reviewed the role of SIRT1 in ALI in terms of its cellular and molecular mechanism, targeting of SIRT1 by non-coding RNAs and drug components, as well as pointing out the value of SIRT1 for clinical diagnosis and prognosis. Based on the current literature, SIRT1 exhibits diverse functionalities and possesses significant therapeutic potential. Targeting SIRT1 may provide new therapeutic ideas for the treatment of ALI.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142264942","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":"Myeloid-derived suppressor cells alleviate adverse ventricular remodeling after acute myocardial infarction","authors":"Yan-Ge Wang, Ding-Hang Wang, Wen-Hui Wei, Xin Xiong, Jing-Jing Wu, Zhan-Ying Han, Long-Xian Cheng","doi":"10.1007/s11010-024-05112-y","DOIUrl":"https://doi.org/10.1007/s11010-024-05112-y","url":null,"abstract":"<p>The fundamental pathophysiological mechanism in the progression of chronic heart failure following acute myocardial infarction (AMI) is ventricular remodeling, in which innate and adaptive immunity both play critical roles. Myeloid-derived suppressor cells (MDSCs) have been demonstrated to function in a range of pathological conditions, such as infections, inflammation, autoimmune diseases, and tumors. However, it is unclear how MDSCs contribute to cardiac remodeling following AMI. This study aimed to identify the function and underlying mechanism of MDSCs in controlling cardiac remodeling following AMI. Following AMI in mice, MDSCs frequencies changed dynamically, considerably increased on day 7 in blood, spleens, lymph nodes and hearts, and decreased afterwards. Consistently, mice with AMI displayed enhanced cardiac function on day 14 post-AMI, reduced infract size and higher survival rates on day 28 post-AMI following the adoptive transfer of MDSCs. Furthermore, MDSCs inhibited the inflammatory response by decreasing pro-inflammatory cytokine (TNF-α, IL-17, Cxcl-1, and Cxcl-2) expression, up-regulating anti-inflammatory cytokine (TGF-β1, IL-10, IL-4, and IL-13) expression, reducing CD3⁺ T cell infiltration in the infarcted heart and enhancing M2 macrophage polarization. Mechanistically, MDSCs improved the release of anti-inflammatory factors (TGF-β1 and IL-10) and decreased the injury of LPS-induced cardiomyocytes in vitro in a manner dependent on cell–cell contact. Importantly, blockade of IL-10 partially abolished the cardioprotective role of MDSCs. This study found that MDSCs contributed to the restoration of cardiac function and alleviation of adverse cardiac remodeling after AMI possibly by inhibiting inflammation.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142203231","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 interplay between oxidative stress, zinc, and metabolic dysfunction in polycystic ovarian syndrome","authors":"Olivia G. Camp, Daniel N. Moussa, Richard Hsu, Awoniyi O. Awonuga, Husam M. Abu-Soud","doi":"10.1007/s11010-024-05113-x","DOIUrl":"https://doi.org/10.1007/s11010-024-05113-x","url":null,"abstract":"<p>Polycystic ovarian syndrome (PCOS) is a functional endocrine disorder characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovarian morphology that has been associated with chronic disease and comorbidities including adverse metabolic and cardiac disorders. This review aims to evaluate the role of oxidative stress and zinc in the metabolic dysfunction observed in PCOS, with a focus on insulin resistance. Recent studies indicate that oxidative stress markers are elevated in PCOS and correlate with hyperandrogenemia, obesity, and insulin resistance. Zinc, an essential trace element, is crucial for metabolic processes, particularly in the pancreas for beta-cell function and glucagon secretion. Insufficient zinc levels have been linked to diabetes, obesity, and lipid metabolism disorders. This review aims to highlight the interplay between oxidative stress, zinc, and metabolic dysfunction in PCOS, suggesting that zinc supplementation could mitigate some metabolic and endocrine manifestations of PCOS.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142226143","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}