Molecular and Cellular Biochemistry最新文献

{"title":"Therapeutic applications and challenges in myostatin inhibition for enhanced skeletal muscle mass and functions.","authors":"Brock Wetzlich, Benard B Nyakundi, Jinzeng Yang","doi":"10.1007/s11010-024-05120-y","DOIUrl":"https://doi.org/10.1007/s11010-024-05120-y","url":null,"abstract":"<p><p>Myostatin, a potent negative regulator of skeletal muscle mass, has garnered significant attention as a therapeutic target for muscle dystrophies. Despite extensive research and promising preclinical results, clinical trials targeting myostatin inhibition in muscle dystrophies have failed to yield substantial improvements in muscle function or fitness in patients. This review details the mechanisms behind myostatin's function and the various inhibitors that have been tested preclinically and clinically. It also examines the challenges encountered in clinical translation, including issues with drug specificity, differences in serum myostatin concentrations between animal models and humans, and the necessity of neural input for functional improvements. Additionally, we explore promising avenues of research beyond muscle dystrophies, particularly in the treatment of metabolic syndromes and orthopedic disorders. Insights from these alternative applications suggest that myostatin inhibition may hold the potential for addressing a broader range of pathologies, providing new directions for therapeutic development.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142350255","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: External Qi of Yan Xin Qigong induces cell death and gene expression alterations promoting apoptosis and inhibiting proliferation, migration and glucose metabolism in small-cell lung cancer cells.","authors":"Xin Yan, Feng Li, Igor Dozmorov, Mark Barton Frank, Ming Dao, Michael Centola, Wei Cao, Dan Hu","doi":"10.1007/s11010-024-05107-9","DOIUrl":"https://doi.org/10.1007/s11010-024-05107-9","url":null,"abstract":"","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142350254","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":"Interconnections of screen time with neuroinflammation.","authors":"Ashish Verma, Anmol Kumar, Satendra Chauhan, Nisha Sharma, Anuradha Kalani, Prakash Chandra Gupta","doi":"10.1007/s11010-024-05123-9","DOIUrl":"https://doi.org/10.1007/s11010-024-05123-9","url":null,"abstract":"<p><p>The increasing prevalence of screen time among modern citizens has raised concerns regarding its potential impact on neuroinflammation and overall brain health. This review examines the complex interconnections between screen time and neuroinflammatory processes, particularly in children and adolescents. We analyze existing literature that explores how excessive digital media use can lead to alterations in neurobiological pathways, potentially exacerbating inflammatory responses in the brain. Key findings suggest that prolonged exposure to screens may contribute to neuroinflammation through mechanisms such as disrupted sleep patterns, diminished cognitive engagement, and increased stress levels. Similarly, we discuss the implications of these findings for mental health and cognitive development, emphasizing the need for a balanced approach to screen time. This review highlights the necessity for further research to elucidate the causal relationships and underlying mechanisms linking screen time and neuroinflammation, thereby informing guidelines for healthy media consumption.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142308057","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":"BsmI, ApaI and FokI variants of vitamin D receptor gene polymorphism as predictors of response to treatment in immune thrombocytopenia patients.","authors":"Rania A Radwan, Walaa A Elsalakawy, Doaa M Abdelaziz, Doaa M Abdelrazek, Sara M Radwan","doi":"10.1007/s11010-024-05100-2","DOIUrl":"https://doi.org/10.1007/s11010-024-05100-2","url":null,"abstract":"<p><p>Vitamin D receptor (VDR) polymorphisms are linked with the incidence and severity of several autoimmune diseases. The current work aimed at evaluating if VDR rs1544410 (BsmI), rs7975232 (ApaI) and rs2228570 (FokI) gene polymorphisms could be predictors of response to steroid treatment in patients with immune thrombocytopenia (ITP). The study involved 75 steroid treatment responders and 75 resistant ITP patients. All participants were subjected to VDR BsmI, ApaI and FokI gene polymorphisms analysis through genotyping by RT-PCR. Carrying the FokI F allele was significantly associated with low vitamin D level and increased risk of developing steroid resistance. Interestingly, the tri-allelic haplotypes BAF and BaF were significantly only present in steroid resistant ITP patients. Thus, the present study suggests that VDR FokI F allele may contribute to ITP pathogenesis and resistance to steroid treatment. Knowing the genetic background of patients helps to individualize treatment to obtain a better outcome.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142291458","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":"Association of high-sensitivity C-reactive protein and hematologic-inflammatory indices with risk of cardiovascular diseases: a population-based study with partial least squares structural equation modeling approach.","authors":"Somayeh Ghiasi Hafezi, Rana Kolahi Ahari, Maryam Saberi-Karimian, Zahra Eslami Giski, Amin Mansoori, Gordon A Ferns, Mahmoud Ebrahimi, Alireza Heidari-Bakavoli, Mohsen Moohebati, Sara Yousefian, Farnaz Farrokhzadeh, Habibollah Esmaily, Majid Ghayour-Mobarhan","doi":"10.1007/s11010-024-05122-w","DOIUrl":"https://doi.org/10.1007/s11010-024-05122-w","url":null,"abstract":"<p><p>Partial least squares structural equation modeling is a simple approach that may be used to determine the factors associated with diseases. In the current study, we aimed to explore the most associated high-sensitivity C-reactive protein (hs-CRP) as well as hematologic-inflammatory indices for the risk of cardiovascular disease (CVD). A total of 7362 healthy (non-CVD) participants aged 35-65 years old from baseline investigation were evaluated in the Phase 2 follow-up. Of these, 1022 individuals were found to have CVDs in the second phase (10-year follow-up) of the Mashhad Stroke and Heart Atherosclerotic Disorder (MASHAD) cohort study. We used partial least squares structural equation modeling to develop a prediction model for association of CVD risk factors and hs-CRP as well as hematologic-inflammatory indices in the study population. According to the study, age had the most significant impact on the presence of CVD. Increasing in age by one unit raises the risk of CVD by 0.166. Also, serum hs-CRP was found to have the second-highest impact on CVD; increasing in age by one unit raises the risk of CVD by 0.042. The study also discovered a strong and significant correlation between red cell distribution width (RDW) and CVD. Moreover, the study found that several factors such as hemoglobin (HGB), neutrophil (NEUT), neutrophil-to-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), and platelet-to-lymphocyte ratio (PLR) have indirect effects on CVD that are mediated by hs-CRP while controlling for age, sex and social-economic factors. Generally, the results showed that age, hs-CRP, and RDW were the most important risk factors on CVD.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142291457","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":"Sacubitril/valsartan attenuated myocardial inflammation, fibrosis, apoptosis and promoted autophagy in doxorubicin-induced cardiotoxicity mice via regulating the AMPKα-mTORC1 signaling pathway.","authors":"Feng Hu, Senbo Yan, Li Lin, Xiaoxia Qiu, Xinghe Lin, Weiwei Wang","doi":"10.1007/s11010-024-05117-7","DOIUrl":"10.1007/s11010-024-05117-7","url":null,"abstract":"<p><p>This study aimed to investigate the potential cardioprotective effects of sacubitril/valsartan (Sac/Val) in mice with doxorubicin (DOX)-induced cardiomyopathy, a common manifestation of cancer therapy-related cardiac dysfunction (CTRCD) associated with DOX. A total of thirty-two mice were equally classified into 4 groups: control group, DOX (total 24 mg/kg), Sac/Val (80 mg/kg), and Sac/Val + DOX (Sac/Val was given from seven days before doxorubicin administration). Neonatal rat ventricular myocytes was exposed to 5 µM of DOX for 6 h in vitro to mimic the in vivo conditions. A variety of techniques were used to investigate cardiac inflammation, fibrosis, apoptosis, and autophagy, including western blot, real-time quantitative PCR (RT-qPCR), immunohistochemistry, and fluorescence. Mice with DOX-induced cardiotoxicity displayed impaired systolic and diastolic function, characterized by elevated levels of cardiac inflammation, fibrosis, cardiomyocyte hypertrophy, apoptosis, and autophagy inhibition in the heart. Treatment with Sac/Val partially reversed these effects. In comparison to the control group, the protein expression of NLRP3, caspase-1, collagen I, Bax, cleaved caspase-3, and P62 were significantly increased, while the protein expression of Bcl-2 and LC3-II were significantly decreased in the myocardial tissues of the Dox-induced cardiomyopathy group. The administration of Sac/Val demonstrated the potential to partially reverse alterations in protein expression within the myocardium of mice with DOX-induced cardiotoxicity by modulating the AMPKα-mTORC1 signaling pathway and suppressing oxidative stress. Additionally, Sac/Val treatment may mitigate Dox-induced apoptosis and inhibition of autophagy in primary cardiomyocytes. Sac/Val seems to be cardioprotective against DOX-induced cardiotoxicity in the pre-treatment mice model. These findings could be attributed to the anti-inflammatory, antioxidant, anti-apoptotic, and de-autophagy effects of Sac/Val through regulation of the AMPKα-mTORC1 signaling pathway.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142291459","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":"Stress-induced extracellular vesicles: insight into their altered proteomic composition and probable physiological role in cancer.","authors":"Vaidehi Bhavsar, Ashish Sahu, Ravindra Taware","doi":"10.1007/s11010-024-05121-x","DOIUrl":"https://doi.org/10.1007/s11010-024-05121-x","url":null,"abstract":"<p><p>EVs (extracellular vesicles) are phospholipid bilayer vesicles that can be released by both prokaryotic and eukaryotic cells in normal as well as altered physiological conditions. These vesicles also termed as signalosomes, possess a distinctive cargo comprising nucleic acids, proteins, lipids, and metabolites, enabling them to play a pivotal role in both local and long-distance intercellular communication. The composition, origin, and release of EVs can be influenced by different physiological conditions and a variety of stress factors, consequently affecting the contents carried within these vesicles. Therefore, identifying the modified contents of EVs can provide valuable insights into their functional role in stress-triggered communication. Particularly, this is important when EVs released from tumor microenvironment are investigated for their role in the development and dissemination of cancer. This review article emphasizes the importance of differential EV shedding and altered proteomic content in response to reduced oxygen concentration, altered levels of glucose and glutamine, pH variations, oxidative stress and Ca²⁺ ion concertation and it is subsequent effects on the behavior of recipient cells.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142291460","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":"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":"20 1","pages":""},"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":"26 1","pages":""},"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":"22 1","pages":""},"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}