Molecular and Cellular Biochemistry最新文献

{"title":"Exploring ferroptosis and miRNAs: implications for cancer modulation and therapy.","authors":"Mobarakeh Ajam-Hosseini, Sadegh Babashah","doi":"10.1007/s11010-024-05169-9","DOIUrl":"https://doi.org/10.1007/s11010-024-05169-9","url":null,"abstract":"<p><p>Ferroptosis is a novel, iron-dependent form of non-apoptotic cell death characterized by the accumulation of lipid reactive oxygen species (ROS) and mitochondrial shrinkage. It is closely associated with the onset and progression of various diseases, especially cancer, at all stages, making it a key focus of research for developing therapeutic strategies. Numerous studies have explored the role of microRNAs (miRNAs) in regulating ferroptosis by modulating the expression of critical genes involved in iron metabolism and lipid peroxidation. Due to their diversity, unique properties, and dynamic expression patterns in diseases, exosomal miRNAs are emerging as promising biomarkers. Exosomes act as biological messengers, delivering miRNAs to target cells through specific internalization, thus influencing the ferroptosis response in recipient cells. This review summarizes the roles of miRNAs, with particular focus on exosomal miRNAs, in ferroptosis and their implications for cancer pathology. By examining the molecular mechanisms of miRNAs, we aim to provide valuable insights into potential therapeutic approaches.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143047154","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":"METTL3: a multifunctional regulator in diseases.","authors":"Na Li, Xiang Wei, Jian Dai, Jinfeng Yang, Sizheng Xiong","doi":"10.1007/s11010-025-05208-z","DOIUrl":"https://doi.org/10.1007/s11010-025-05208-z","url":null,"abstract":"<p><p>N6-methyladenosine (m⁶A) methylation is the most prevalent and abundant internal modification of mRNAs and is catalyzed by the methyltransferase complex. Methyltransferase-like 3 (METTL3), the best-known m⁶A methyltransferase, has been confirmed to function as a multifunctional regulator in the reversible epitranscriptome modulation of m⁶A modification according to follow-up studies. Accumulating evidence in recent years has shown that METTL3 can regulate a variety of functional genes, that aberrant expression of METTL3 is usually associated with many pathological conditions, and that its expression regulatory mechanism is related mainly to its methyltransferase activity or mRNA posttranslational modification. In this review, we discuss the regulatory functions of METTL3 in various diseases, including metabolic diseases, cardiovascular diseases, and cancer. We focus mainly on recent progress in identifying the downstream target genes of METTL3 and its underlying molecular mechanisms and regulators in the above systems. Studies have revealed that the use of METTL3 as a therapeutic target and a new diagnostic biomarker has broad prospects. We hope that this review can serve as a reference for further studies.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143033702","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":"Acid sphingomyelinase downregulation alleviates diabetic myocardial fibrosis in mice.","authors":"Changnong Chen, Yang Ji, Hao Liu, Lihua Pang, Jing Chen, Huanzhen Chen, Yujie Yao, Jinhao Ye, Sha Wang, Shiming Liu, Yun Zhong","doi":"10.1007/s11010-025-05206-1","DOIUrl":"https://doi.org/10.1007/s11010-025-05206-1","url":null,"abstract":"<p><p>Increased activity of acid sphingomyelinase (ASMase) has been linked to diabetes and organ fibrosis. Nevertheless, the precise influence of ASMase on diabetic myocardial fibrosis and the corresponding molecular mechanisms remain elusive. In this study, we aim to elucidate whether ASMase contributes to diabetic myocardial fibrosis through the phosphorylation mediated by MAPK, thereby culminating in the development of diabetic cardiomyopathy (DCM). In vitro experiments utilized cardiac fibroblasts (CFs) isolated from wild-type mice (WT). For in vivo studies, ASMase knockout mice were generated through TALEN gene editing technology. Additionally, a diabetes mellitus model was established by intraperitoneal injection of Streptozotocin (STZ), involving both ASMase knockdown mice (ASMase^+/--STZ) and WT mice. CFs were subjected to incubation with amitriptyline (AMP) (2.5 μM), advanced glycation end products (AGEs), and small interfering RNA (siRNA) over a duration of 24 h. Experimental assessments encompassed EdU incorporation, transwell assays, and fluorescence staining, aimed at elucidating the functional characteristics of cardiac fibroblasts. The quantification of collagen I, phosphorylated MAPK levels within both cellular and murine cardiac contexts was accomplished through Western blot analysis. In the ASMase^±-STZ group, mice exhibited attenuated myocardial fibrosis and ameliorated cardiac diastolic function in comparison to the WT-STZ group. Furthermore, treatment of CFs with AMP and siRNA demonstrated a suppressive effect on the proliferation and fibrotic expression induced by AGEs in CFs. Our investigation unveiled that ASMase modulates myocardial fibrosis through the TGF-β-Smad3 and MAPK pathways, elucidating the intricate molecular mechanisms underlying the observed effects. Our findings indicate that ASMase plays a vital role in myocardial fibrosis in DCM, providing a foundation for developing new therapeutic strategies for the prevention and control of DCM.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143033701","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":"Correction to: Macrophage energy metabolism in cardiometabolic disease.","authors":"Angela Wong, Qiuyu Sun, Ismail I Latif, Qutuba G Karwi","doi":"10.1007/s11010-024-05197-5","DOIUrl":"https://doi.org/10.1007/s11010-024-05197-5","url":null,"abstract":"","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143024025","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 bone-vascular axis: the link between osteoporosis and vascular calcification.","authors":"Yue Sun, Dageng Huang, Yan Zhang","doi":"10.1007/s11010-025-05210-5","DOIUrl":"https://doi.org/10.1007/s11010-025-05210-5","url":null,"abstract":"<p><p>Osteoporosis and vascular calcification are chronic metabolic diseases threatening the health of aging people. The incidence of osteoporosis and vascular calcification increases year by year, and has drawn much attention from the scientific and clinical area. Many studies have found that osteoporosis and vascular calcification are not completely independent, but there are close correlations between them in the pathogenesis and underlying mechanisms. The underlying mechanisms of osteoporosis and vascular calcification include aging, oxidative stress, inflammatory response, lipid metabolism, calcium and phosphorus metabolism, vitamins, autophagy, and extracellular vesicles. This review updates the current understanding of the correlation and underlying mechanisms of osteoporosis and vascular calcification, and highlights the complexity of the bone-vascular axis, aiming to provide novel ideas for the prevention and treatment of osteoporosis and vascular calcification.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143029205","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":"Synaptic-mitochondrial transport: mechanisms in neural adaptation and degeneration.","authors":"Yang Ding, Huan Yang, Jie Gao, Can Tang, Yu-Yuan Peng, Xin-Mei Ma, Sen Li, Hai-Yan Wang, Xiu-Min Lu, Yong-Tang Wang","doi":"10.1007/s11010-025-05209-y","DOIUrl":"https://doi.org/10.1007/s11010-025-05209-y","url":null,"abstract":"<p><p>Synaptic plasticity is the basis for the proper functioning of the central nervous system. Synapses are the contact points between neurons and are crucial for information transmission, the structure and function of synapses change adaptively based on the different activities of neurons, thus affecting processes such as learning, memory, and neural development and repair. Synaptic activity requires a large amount of energy provided by mitochondria. Mitochondrial transport proteins regulate the positioning and movement of mitochondria to maintain normal energy metabolism. Recent studies have shown a close relationship between mitochondrial transport proteins and synaptic plasticity, providing a new direction for the study of adaptive changes in the central nervous system and new targets for the treatment of neurodegenerative diseases.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008361","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":"Epigallocatechin 3-gallate-induced neuroprotection in neurodegenerative diseases: molecular mechanisms and clinical insights.","authors":"Md Rezaul Islam, Abdur Rauf, Sumiya Akter, Happy Akter, Md Ibrahim Khalil Al-Imran, Samiul Islam, Meherun Nessa, Chaity Jahan Shompa, Md Nabil Rihan Shuvo, Imtiaz Khan, Waleed Al Abdulmonem, Abdullah S M Aljohani, Muhammad Imran, Marcello Iriti","doi":"10.1007/s11010-025-05211-4","DOIUrl":"https://doi.org/10.1007/s11010-025-05211-4","url":null,"abstract":"<p><p>Neurodegenerative diseases (NDs) are caused by progressive neuronal death and cognitive decline. Epigallocatechin 3-gallate (EGCG) is a polyphenolic molecule in green tea as a neuroprotective agent. This review evaluates the therapeutic effects of EGCG and explores the molecular mechanisms that show its neuroprotective properties. EGCG protects neurons in several ways, such as by lowering oxidative stress, stopping Aβ from aggregation together, changing cell signaling pathways, and decreasing inflammation. Furthermore, it promotes autophagy and improves mitochondrial activity, supporting neuronal survival. Clinical studies have demonstrated that EGCG supplementation can reduce neurodegenerative biomarkers and enhance cognitive function. This review provides insights into the molecular mechanisms and therapeutic potential of EGCG in treating various NDs. EGCG reduces oxidative stress by scavenging free radicals and enhancing antioxidant enzyme activity, aiding neuronal defense. It also protects neurons and improves cognitive abilities by inhibiting the toxicity and aggregation of Aβ peptides. It changes important cell signaling pathways like Nrf2, PI3K/Akt, and MAPK, which are necessary for cell survival, cell death, and inflammation. Additionally, it has strong anti-inflammatory properties because it inhibits microglial activation and downregulates pro-inflammatory cytokines. It improves mitochondrial function by reducing oxidative stress, increasing ATP synthesis, and promoting mitochondrial biogenesis, which promotes neurons' survival and energy metabolism. In addition, it also triggers autophagy, a cellular process that breaks down and recycles damaged proteins and organelles, eliminating neurotoxic aggregates and maintaining cellular homeostasis. Moreover, it holds significant promise as an ND treatment, but future research should focus on increasing bioavailability and understanding its long-term clinical effects. Future studies should focus on improving EGCG delivery and understanding its long-term effects in therapeutic settings. It can potentially be a therapeutic agent for managing NDs, indicating a need for further research.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008352","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 role of α-tocopherol in the prevention and treatment of Alzheimer's disease.","authors":"Michał Pelczarski, Szymon Wolaniuk, Monika Zaborska, Jakub Sadowski, Anna Sztangreciak-Lehun, Rafał Jakub Bułdak","doi":"10.1007/s11010-025-05214-1","DOIUrl":"https://doi.org/10.1007/s11010-025-05214-1","url":null,"abstract":"<p><p>Scientific reports from various areas of the world indicate the potential role of tocopherols (vitamin E) in particular α-tocopherol in the prevention and therapy of Alzheimer's disease. The current phenomenon is related to the growing global awareness of eating habits and is also determined by the need to develop the prevention, management and therapy of Alzheimer's disease. This article is a review of current research on the action of the active form of vitamin E-α-tocopherol and its impact on the development and course of Alzheimer's disease. Additionally, to contrast this information, selected primary research on this topic was included. The aim of this article is to analyze and summarize the available scientific information on the effects of the active form of vitamin E, α-tocopherol, on the development and course of Alzheimer's disease. In the structure of the review, particular attention was paid to the analysis of the pathophysiological processes of the disease and the biochemical features of the action of α-tocopherol. To discuss the relationship between the effect of α-tocopherol and the occurrence of Alzheimer's disease, a literature review was conducted using the following databases: PubMed, Google Scholar, and Elsevier. During the search process, the following keywords were used: \"tocopherols\", \"vitamin E\", \"α-tocopherol\", \"Alzheimer's disease\" in various combinations. The process was conducted in accordance with the adopted search strategy taking into account the inclusion and exclusion criteria. Alzheimer's disease (AD) is the most common, irreversible neurodegenerative disease, so many scientists are actively looking for substances and/or strategies to prevent its development and to slow down its course in patients. Alpha-tocopherols (ATF) are a factor that inhibits the pathophysiological processes associated with the development of AD by reducing the formation of atherogenic amyloid B (AB). Additionally, this type of tocopherols has antioxidant and anti-inflammatory properties and has a positive effect on the metabolic functioning of mitochondria. It has been shown that a higher intake of α-tocopherol (ATF) was associated with a reduced risk of developing dementia and the occurrence of mild types of cognitive impairment (MCI). Various sources indicate an insufficient supply of ATF in the diet. ATF supplementation may potentially help to slow down the course of Alzheimer's disease, which is why this substance may be popularized in the treatment of this disease in the future. However, there is a need for further research on this issue.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008364","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":"Tumor microenvironment noise-induced polarization: the main challenge in macrophages' immunotherapy for cancer.","authors":"Jesus Sierra, Ugo Avila-Ponce de León, Pablo Padilla-Longoria","doi":"10.1007/s11010-025-05205-2","DOIUrl":"https://doi.org/10.1007/s11010-025-05205-2","url":null,"abstract":"<p><p>Disturbance of epigenetic processes can lead to altered gene function and malignant cellular transformation. In particular, changes in the epigenetic landscape are a central topic in cancer biology. The initiation and progression of cancer are now recognized to involve both epigenetic and genetic alterations. In this paper, we study the epigenetic mechanism (related to the tumor microenvironment) responsible for increasing tumor-associated macrophages that promote the occurrence and metastasis of tumor cells, support tumor angiogenesis, inhibit T-cell-mediated anti-tumor immune response, and lead to tumor progression. We show that the tumor benefits from the macrophages' high degree of plasticity and larger epigenetic basins corresponding to phenotypes that favor cancer development through a process that we call noise-induced polarization. Moreover, we propose a mechanism to promote the appropriate epigenetic stability for immunotherapies involving macrophages, which includes p53 and APR-246 (eprenetapopt). Our results show that a combination therapy may be necessary to ensure the proper epigenetic stability of macrophages, which otherwise will contribute to cancer progression. On the other hand, we conclude that macrophages may remain in the anti-tumoral state in types of cancer that exhibit less TP53 mutation, like colorectal cancer; in these cases, macrophages' immunotherapy may be more suitable. We finally mention the relevance of the epigenetic potential (Waddington's landscape) as the backbone for our study, which encapsulates the biological information of the system.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008399","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":"Cardiovascular protective effects of natural flavonoids on intestinal barrier injury.","authors":"Peng Zhou, Hui-Juan Xu, Liang Wang","doi":"10.1007/s11010-025-05213-2","DOIUrl":"https://doi.org/10.1007/s11010-025-05213-2","url":null,"abstract":"<p><p>Natural flavonoids may be utilized as an important therapy for cardiovascular diseases (CVDs) caused by intestinal barrier damage. More research is being conducted on the protective properties of natural flavonoids against intestinal barrier injury, although the underlying processes remain unknown. Thus, the purpose of this article is to present current research on natural flavonoids to reduce the incidence of CVDs by protecting intestinal barrier injury, with a particular emphasis on intestinal epithelial barrier integrity (inhibiting oxidative stress, regulating inflammatory cytokine expression, and increasing tight junction protein expression). Furthermore, the mechanisms driving intestinal barrier injury development are briefly explored, as well as natural flavonoids having CVD-protective actions on the intestinal barrier. In addition, natural flavonoids with myocardial protective effects were docked with ZO-1 targets to find natural products with higher activity. These natural flavonoids can improve intestinal mechanical barrier function through anti-oxidant or anti-inflammatory mechanism, and then prevent the occurrence and development of CVDs.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008372","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}