Molecular and Cellular Biochemistry最新文献

{"title":"The role of physical exercise in modulating microRNAs expression in acute myocardial infarction: a review.","authors":"Raphael Furtado Marques, Marcelo Souza de Andrade, Andressa Coelho Ferreira, Carlos José Moraes Dias, Nivaldo de Jesus Silva Soares Junior, Carlos Alberto Alves Dias Filho, Rachel Melo Ribeiro","doi":"10.1007/s11010-025-05229-8","DOIUrl":"10.1007/s11010-025-05229-8","url":null,"abstract":"<p><p>MicroRNAs (miRNAs) have emerged as promising tools for diagnosis and treatment in numerous pathophysiological processes, including cardiovascular diseases (CVD). In this context, acute myocardial infarction (AMI) is one of the leading causes of death by CVD worldwide. In this sense, physical exercise (PE) is considered a non-pharmacological strategy to reduce the complex alterations in AMI. This study is an integrative review of the literature to explore the effects of PE on the cardiomyocyte post-AMI, including an understanding of the mechanisms by which the PE acts on the miRNAs expression. A review was performed on PubMed, Scopus, and Web of Science. After the searches, all records were imported into the Mendeley software, and duplicate articles were removed. The year of publication of the papers was not limited. 19 studies were performed on animal models, 10 in experimental models using rats, and 08 in models with mice and only one study was carried out on patients with AMI. The results showed the potential use of miRNAs as diagnostic tools and attractive biomarkers for treating AMI. In addition, PE can regulate miRNAs expression in the myocardial cell, promotes apoptosis resistance, autophagy regulation, lower cardiac fibrosis and cardiac hypertrophy, and higher angiogenesis through the signaling of miRNAs. The main microRNAs mitigating the deleterious effects of AMI and modulated by PE were miRNA-222, miRNA-1192, miRNA-146, and miRNA-126. PE modulates the expression of specific miRNAs that support cardiac function, promoting cardioprotective effects or facilitating cardiac recovery post-AMI.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"3593-3603"},"PeriodicalIF":3.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143425857","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":"Accumulation of microtubule-associated protein tau promotes hepatocellular carcinogenesis through inhibiting autophagosome-lysosome fusion.","authors":"Xuemin Liu, Zhiwei Hao, Huanhuan He, Xuan Wang, Wenqi Wang, Xiji Shu, Binlian Sun, Zhiyong Hu, Shaobo Hu, Xiaoying Hou, Yue Xiao, Hongyan Zhou, Yuchen Liu, Jianzhi Wang, Zhengqi Fu","doi":"10.1007/s11010-024-05193-9","DOIUrl":"10.1007/s11010-024-05193-9","url":null,"abstract":"<p><p>Dysregulated expression of microtubule-associated protein tau (MAPT) has been reported in a variety of human cancers. However, whether and how Tau influences hepatocellular carcinogenesis remains elusive. This study was aimed to investigate the role and the underlying mechanism of Tau in the proliferation, invasion, migration and sorafenib sensitivity of hepatocellular carcinoma (HCC) cells. An increased level of Tau was found in the primary tumor samples of HCC compared with the adjacent normal liver tissues, and the increase of Tau was positively correlated with p62 evidenced by the data obtained from The Cancer Genome Atlas (TCGA), Gene Expression Profiling Interactive Analysis (GEPIA), and human samples from HCC patients. The high Tau expression was also correlated with a poorer survival in HCC patients demonstrated by using the GEPIA survival analysis and OncoLnc database. Further studies showed that Tau overexpression promoted the growth, invasion and migration and decreased sorafenib sensitivity in HepG2 and Huh7 cells; Tau also accelerated growth of xenograft tumors with blockage of autophagosome-lysosome fusion. Finally, overexpressing Tau inhibited AMPK, which contributed to Tau-induced promotion of hepatocellular carcinogenesis. In conclusion, our study provides the proof-of-concept evidence validating Tau as an attractive HCC target.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"3621-3635"},"PeriodicalIF":3.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882545","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":"Advancing Parkinson's diagnosis: seed amplification assay for α-synuclein detection in minimally invasive samples.","authors":"Elizabeth Carrazana, Leonardo Montalbán-Gutiérrez, Pedro Chana-Cuevas, Natalia Salvadores","doi":"10.1007/s11010-024-05190-y","DOIUrl":"10.1007/s11010-024-05190-y","url":null,"abstract":"<p><p>Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by tremor, rigidity, and bradykinesia, beginning with early loss of dopaminergic neurons in the ventrolateral substantia nigra and advancing to broader neurodegeneration in the midbrain. The clinical heterogeneity of PD and the lack of specific diagnostic tests present significant challenges, highlighting the need for reliable biomarkers for early diagnosis. Alpha-synuclein (α-Syn), a protein aggregating into Lewy bodies and neurites in PD patients, has emerged as a key biomarker due to its central role in PD pathophysiology and potential to reflect pathological processes. Additionally, α-Syn allows earlier differentiation between PD and other neurodegenerative disorders with similar symptoms. Currently, detection of α-Syn pathology in post-mortem brain tissue remains the primary means of achieving a conclusive diagnosis, often revealing significant misdiagnoses. Seed amplification assay (SAA), initially developed for prion diseases, has been adapted to detect α-Syn aggregates in cerebrospinal fluid, showing promise for early diagnosis. Recent studies have demonstrated that SAA can also detect α-Syn aggregates in peripheral samples collected via minimally invasive procedures, such as skin, olfactory mucosa, saliva, and blood. However, the lack of standardized protocols limits clinical application. Standardizing protocols is essential to improve assay reliability and enable accurate patient identification for emerging therapies. This review examines studies on SAA for detecting α-Syn aggregates in minimally invasive samples, focusing on sample collection, processing, and reaction conditions.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"3297-3314"},"PeriodicalIF":3.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142932308","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":"MAPK signaling mediated intestinal inflammation induced by endoplasmic reticulum stress and NOD2.","authors":"Siyuan Peng, Yan Zhao, Wang Jiang, Yan Long, Tian Hu, Mengling Li, Jinyue Hu, Yueming Shen","doi":"10.1007/s11010-025-05212-3","DOIUrl":"10.1007/s11010-025-05212-3","url":null,"abstract":"<p><p>Endoplasmic reticulum (ER) stress is crucially involved in inflammatory bowel disease (IBD), but the mechanisms remain incompletely understood. This study aimed to elucidate how ER stress promotes inflammation in IBD. ER stress marker Grp78 and NOD2 in colon tissues of Crohn's disease (CD) patients and IBD model mice were detected by immunohistochemical analysis. THP-1 cells were exposed to ER stress and the expression of NOD2 and inflammatory cytokines was detected by PCR. We found that ER stress markers Grp78 and NOD2 were upregulated in intestinal tissues of CD patients and in THP-1 cells exposed to ER stress. ER stress inhibitor reduced Grp78 and NOD2 expression in colitis model mice and alleviated colitis. ER stress inducer cooperated with NOD2 ligand MDP to upregulate TNF-α, IL-8 and IL-1β, and activate MAPK signaling in THP-1 cells. Moreover, inhibitors of MAPK signaling led to the downregulation of IL-1β, IL-8 and TNF-α in THP-1 cells stimulated by ER stress inducer and MDP. In conclusion, ER stress upregulates NOD2 and promotes inflammation in IBD, at least partially due to the activation of MAPK pathway.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"3709-3717"},"PeriodicalIF":3.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142979418","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":"Current understanding of PEAK family members in regulation of cellular signaling pathways and cancer therapy.","authors":"Mana Alavi, Raheleh Roudi, Alberto D'Angelo, Navid Sobhani, Fatemeh Safari","doi":"10.1007/s11010-025-05219-w","DOIUrl":"10.1007/s11010-025-05219-w","url":null,"abstract":"<p><p>Cancer evades therapy by multiple mechanisms, leading to uncontrolled cell growth and metastasis. Targeted therapies have shown promise in treating cancer by focusing on pathways within cancer cells. The PEAK family, comprising PEAK1 (SgK269), PEAK2 (SgK223/Pragmin), and the latest addition, PEAK3 (C19orf35), plays a crucial role in modulating cellular processes. Dysregulation and hyperactivity of these proteins, through overexpression or mutations, are associated with a wide range of cancers. This review delves into the different roles of the PEAK family members in regulating cell signaling pathways and highlights their potential in cancer therapy.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"3521-3533"},"PeriodicalIF":3.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143374317","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":"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":"3343-3362"},"PeriodicalIF":3.5,"publicationDate":"2025-06-01","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}

{"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":"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":"3749-3763"},"PeriodicalIF":3.5,"publicationDate":"2025-06-01","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":"MTMR7 attenuates the proliferation and migration of pulmonary arterial smooth muscle cells in pulmonary hypertension by suppressing ERK/STAT3 signaling.","authors":"Jia Wang, Bing Xuan, Baomei Song, Ting Wang, Cong Lan, Wei Guo, Yongjian Yang, Xiongshan Sun","doi":"10.1007/s11010-025-05217-y","DOIUrl":"10.1007/s11010-025-05217-y","url":null,"abstract":"<p><p>Myotubularin-related protein 7 (MTMR7) represses proliferation in several cell types. However, the role of MTMR7 in pulmonary arterial smooth muscle cells (PASMCs) and pulmonary hypertension (PH) is unknown. The present study aimed to explore the role of MTMR7 in PH, as well as in the proliferation and migration of PASMCs. A monocrotaline (MCT)-induced PH mouse model was established. Mtmr7-transgenic (Mtmr7-Tg) mice and an adenovirus carrying the Mtmr7 vector (Ad-Mtmr7) were used to achieve MTMR7 overexpression in vivo and in vitro, respectively. Ultrasound and morphological analyses were used to evaluate the severity of PH. Cell counting kit-8 (CCK-8) and Ki-67 immunofluorescence staining were used to assess the proliferation of PASMCs. Wound-healing and transwell assays were used to assess cell migration. MTMR7 was upregulated in hypoxia-stimulated PASMCs and pulmonary arteries of MCT-treated mice. When compared with wild-type mice, PH-associated symptoms were significantly ameliorated in Mtmr7-Tg mice after MCT treatment when compared to wild-type mice. MTMR7 overexpression suppressed the proliferation and migration of PASMCs induced by hypoxia. Further experiments revealed that MTMR7 inhibited the phosphorylation levels of ERK1/2 and STAT3 both in vivo and in vitro. Restoring either ERK1/2 or STAT3 eliminated the protective role of MTMR7 against PH. Additionally, restoring ERK1/2 also reversed MTMR7-mediated STAT3 dephosphorylation. Our study highlights the inhibitory role of MTMR7 in PH and in the proliferation and migration of PASMCs and thus provides a novel potent therapeutic strategy for treating PH.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"3799-3812"},"PeriodicalIF":3.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143365510","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":"Exogenous hydrogen sulfide improves non-alcoholic fatty liver disease by inhibiting endoplasmic reticulum stress/NLRP3 inflammasome pathway.","authors":"Xiaodi Fu, Qi Zhang, Yuhang Chen, Ying Li, Honggang Wang","doi":"10.1007/s11010-025-05220-3","DOIUrl":"10.1007/s11010-025-05220-3","url":null,"abstract":"<p><p>Non-alcoholic fatty liver disease (NAFLD) is a common chronic liver disease worldwide, and its exact pathogenesis has not been fully studied. Hydrogen sulfide (H₂S) is the third gas signaling molecule discovered in mammals, following nitric oxide and carbon monoxide. It has the effects of anti-inflammation, anti-apoptosis, and so on, thereby playing an important role in many diseases. However, the role and mechanism of exogenous H₂S in NAFLD are not fully understood. In this study, we constructed in vitro and in vivo NAFLD models by feeding mice a high-fat diet and stimulating hepatocytes with palmitic acid, respectively, to investigate the improvement effect and mechanism of exogenous H₂S on NAFLD. The results showed that NaHS (a donor of H₂S) treatment alleviated lipid accumulation, inflammation, apoptosis and pyroptosis, and downregulated endoplasmic reticulum (ER) stress and nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NRRP3) inflammasome in NAFLD. The activation of NLRP3 inflammasome weakened NaHS improvement of NAFLD, indicating that exogenous H₂S ameliorated NAFLD by inhibiting NLRP3 inflammasome-mediated lipid synthesis, inflammation, apoptosis and pyroptosis. Similarly, the activation of ER stress weakened NaHS improvement of NAFLD and NaHS inhibition of NLRP3 inflammasome, indicating that exogenous H₂S suppressed NLRP3 inflammasome by downregulating ER stress, thus improving NAFLD. Additionally, the protein expressions of NLRP3 and cleaved caspase-1 were downregulated after inhibiting the reactive oxygen species (ROS)/extracellular signal-regulated kinases (ERK) and ROS/thioredoxin-interacting protein (TXNIP) pathways, indicating that ER stress activated NLRP3 inflammasome through the ROS/ERK and ROS/TXNIP pathways. In conclusion, our results indicated that exogenous H₂S inhibited NLRP3 inflammasome-mediated hepatocytes inflammation, lipid synthesis, apoptosis and pyroptosis by downregulating ER stress, thereby improving NAFLD; Furthermore, ER stress activated NLRP3 inflammasome through the ROS/ERK and ROS/TXNIP pathways in NAFLD. ER stress/NLRP3 inflammasome is expected to become a new target of H₂S for treating NAFLD.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"3813-3839"},"PeriodicalIF":3.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143374320","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":"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":"3399-3411"},"PeriodicalIF":3.5,"publicationDate":"2025-06-01","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}