Molecular and Cellular Biochemistry最新文献

{"title":"Interconnection between gut microbial metabolites and mitochondrial ROS production: implications for cellular health.","authors":"Priyanka Gupta, Sumit Dutta, Krishanu Dutta, Piyush Bhattacharjee, Arjama Hazra, Rajiv Jash","doi":"10.1007/s11010-025-05397-7","DOIUrl":"https://doi.org/10.1007/s11010-025-05397-7","url":null,"abstract":"<p><p>Trillions of microbes inhabit the human gut and engage in diverse biological processes by secreting different metabolites. These metabolites influence mitochondrial function and produce ROS. This gut-mitochondrial communication plays a pivotal role in regulating cellular homeostasis, energy production, and oxidative stress management, all required for optimal health. Short-chain fatty acids, secondary bile acids, amines, and gaseous metabolites are major gut metabolites that aid in governing mitochondrial processes to facilitate effective energy production and avoid oxidative damage. In the case of damaged mitochondrial function, it can alter gut flora (dysbiosis), resulting in inflammation and assisting a number of diseases such as multiple sclerosis, Alzheimer's disease, IgA nephropathy, inflammatory bowel disease, and colorectal cancer. The gut-mitochondria axis is a multifaceted interaction that regulates a cell's energy homeostasis and provides novel therapeutic opportunities. Probiotics, prebiotics, dietary modifications, and metabolite therapies have the potential to restore gut-microbe balance, enhance mitochondrial function, and reduce oxidative stress. These measures have the potential for new treatments for many diseases by modulating the gut-mitochondria axis. This review surveys interactions among gut microbiota, mitochondrial ROS, and the gut-mitochondria axis, describing how such relationships affect health and disease.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145200374","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":"Metabolomics of abdominal adipose tissue samples collected from patients with obesity - a critical review.","authors":"Alina Jaroch","doi":"10.1007/s11010-025-05399-5","DOIUrl":"https://doi.org/10.1007/s11010-025-05399-5","url":null,"abstract":"<p><p>Obesity is a multifactorial metabolic disorder characterized by excessive fat accumulation and associated with numerous health risks, including insulin resistance, cardiovascular disease, and metabolic syndrome. Adipose tissue, particularly subcutaneous (SAT) and visceral (VAT) fat, plays a central role in metabolic regulation, yet its biochemical properties and functions differ significantly. While metabolomics offers a promising approach to studying adipose tissue at a molecular level, significant methodological limitations and inconsistencies in study design undermine the reliability of current findings. Although VAT is frequently characterized by a pro-inflammatory and lipolytic metabolic profile, whereas SAT is more involved in lipid storage and insulin, these generalizations overlook important depot-specific variations and fail to address the heterogeneity within adipose tissue. This critical review evaluates existing metabolomic studies, identifying key discrepancies in lipid metabolism, energy homeostasis, and inflammation-related pathways across VAT and SAT. It highlights the need for improved standardization in metabolomic analyses, greater inclusion of diverse populations, and more robust longitudinal studies. By addressing these issues, future research can provide more precise insights into adipose tissue's role in obesity-related metabolic dysfunction and better inform clinical strategies for obesity management.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145192146","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":"Monoamine oxidases are mediators of oxidative stress in human varicose Veins: interactions with obesity, inflammation, and angiotensin II.","authors":"Sonia Raţiu, Adrian Sturza, Paul S Muntean, Claudia Borza, Tiberiu Bratu, Danina M Muntean","doi":"10.1007/s11010-025-05398-6","DOIUrl":"https://doi.org/10.1007/s11010-025-05398-6","url":null,"abstract":"<p><p>Chronic venous disease (CVD) and its clinical manifestation, the varicose veins (VVs), are characterized by progressive structural and functional alterations of the venous walls, with obesity/overweight being one of the most frequent comorbidities. Monoamine oxidases (MAO-A and MAO-B) are mitochondrial flavoenzymes responsible for the constant generation of hydrogen peroxide (H₂O₂) during the catabolism of biogenic monoamines and neurotransmitters that contribute, when upregulated, to the oxidative stress in most mammalian tissues. However, their role in the VV pathophysiology and its modulation by vasoactive stimuli such as angiotensin II (Ang II) remains unclear. This exploratory study was double-aimed i) to assess MAO expression in human VV samples in relation to obesity and systemic inflammation and ii) to determine the impact of pharmacological MAO inhibition on oxidative stress under basal and Ang II-stimulated conditions. To this aim, 20 patients with VV and an indication for cryostripping were randomized according to their body mass index (BMI) into obese (n = 10) and non-obese (n = 10) groups, and VV samples were harvested and used to assess the following: i) MAO-A and MAO-B gene expression by qRT-PCR, as well as expression and localization by immunofluorescence, and ii) H₂O₂ by means of the ferrous xylenol orange oxidation (FOX) assay. Furthermore, the effect of selective MAO inhibition (clorgyline 10 μM for MAO-A, selegiline 10 μM for MAO-B) was tested ex vivo both at baseline and following acute stimulation with Ang II (100 nM). We showed that both MAO-A and MAO-B are constitutively expressed in the human venous walls, with higher levels in the varicose veins than in the adjacent perforator veins. The obese patients with inflammatory status (elevated serum C-reactive protein) had significantly increased MAO-A (but not MAO-B) expression as compared to the non-obese controls (p < 0.01). Acute ex vivo incubation with Ang II further enhanced the expression of both isoforms and increased H₂O₂ generation. MAO inhibition significantly mitigated the oxidative stress in both non-stimulated and Ang II-stimulated samples, regardless of the presence or absence of obesity. In conclusion, MAO isoforms, in particular MAO-A, are upregulated in the human varicose veins and can be further induced by Ang II, especially in the setting of obesity associated with low-grade inflammation. MAO contributed to the local oxidative stress, which was significantly reduced by its pharmacological inhibition with MAO-A and B inhibitors, thus pointing to MAO as a potential therapeutic target in patients with CVD.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145186373","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":"FKH domain-mediated nuclear FOXP3 suppresses gastric cancer malignancy via c-MYC/CDKN1A regulation, EMT inhibition, and PI3K/AKT signaling modulation.","authors":"Yu Chen, Xia Zhao, Yuze Zhu, Ling Xu, Juanjuan Wang, Zheyi Chen, Hui Chen, Tingting Rong, Yanhui Ma, Yi Liu, Yunlan Zhou, Yingxia Zheng, Lisong Shen, Guohua Xie","doi":"10.1007/s11010-025-05387-9","DOIUrl":"https://doi.org/10.1007/s11010-025-05387-9","url":null,"abstract":"<p><p>Gastric cancer (GC) remains a primary contributor to cancer-associated deaths worldwide, especially in East Asia. We investigated the function of nuclear-localized full-length FOXP3 (FOXP3FL) as an oncosuppressive factor in GC. Total FOXP3 was markedly reduced in GC tissues versus adjacent normal mucosa, with distinct cytoplasmic and nuclear patterns. Functional assays revealed that nuclear overexpression of FOXP3FL suppresses proliferation, migration, and invasion of GC cells in vitro and in vivo and promotes cellular senescence in vivo. Mechanistically, FOXP3FL directly represses MYC transcription and induces CDKN1A, thereby restraining proliferation and metastasis. These transcriptional changes, together with concomitant PTEN upregulation and PI3K-P110α downregulation, collectively attenuate PI3K/AKT signaling and impair epithelial-mesenchymal transition (EMT) in FOXP3FL-expressing GC cells. The forkhead (FKH) domain is essential: its deletion yields cytoplasmic FOXP3ΔFKH, which loses transcriptional control and antitumor activity. Our findings underscore nuclear-localized FOXP3FL as a tumor suppressor whose FKH domain is integral to its suppressive function.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145137999","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":"Downregulation of Tra2α and Tra2β suppresses lipopolysaccharide-induced inflammation in macrophages by regulating MyD88 mRNA alternative splicing.","authors":"Yu Fu, Luyao Zhang, Yanjing Wang, Bo Cheng, Weiye Shi, Peiyuan Chen, Jinyu Liu, Xiaolei Zhou, Yingze Wang","doi":"10.1007/s11010-025-05394-w","DOIUrl":"https://doi.org/10.1007/s11010-025-05394-w","url":null,"abstract":"<p><p>RNA binding proteins (RBPs) play a pivotal role in the posttranscriptional regulation of inflammatory processes. Transformer-2 (Tra2) is an evolutionarily conserved RBP that regulates mRNA alternative splicing, encoding two homologous proteins in vertebrates, Tra2α and Tra2β. Dysregulation of Tra2α or Tra2β may lead to the development of several inflammatory diseases. However, the roles of Tra2α and Tra2β in inflammation remain unclear. In the current research, the expression levels of Tra2α and Tra2β were upregulated in RAW264.7 macrophage cells stimulated by lipopolysaccharide (LPS). Downregulation of Tra2α or Tra2β inhibited the expression of inflammatory factors induced by LPS. Notably, combined suppression of Tra2α and Tra2β cooperatively reduced LPS-activated inflammation and suppressed the activation of NFκB and MAPK pathways. Myeloid differentiation primary response gene 88 (MyD88), a crucial adaptor in the TLR4 pathway, expresses splicing variants MyD88-L and MyD88-S, which exert pro-inflammatory and anti-inflammatory effects, respectively. We found that Tra2α and Tra2β proteins interacted with MyD88 mRNA. Moreover, downregulation of Tra2α and Tra2β promoted the expression of MyD88-S mRNA variants, thereby modulating the inflammatory response. Therefore, our findings demonstrated that Tra2α and Tra2β cooperatively regulated inflammation by modulating the alternative splicing of MyD88 in LPS-stimulated macrophages. These mechanistic insights into Tra2-mediated regulation of macrophage inflammation may provide novel therapeutic targets for treating inflammatory diseases.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145124804","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":"Mitochondrial abnormalities in nondiabetic and nonhypertensive glomerular diseases: a comprehensive review.","authors":"Baris Afsar, Rengin Elsurer, Krista L Lentine","doi":"10.1007/s11010-025-05393-x","DOIUrl":"https://doi.org/10.1007/s11010-025-05393-x","url":null,"abstract":"<p><p>Glomerulonephritis (GN) is a general term which encompasses various types of glomerular disorders characterized by damage to the capillary endothelium, basement membrane, podocytes, mesangium, or parietal epithelial cells with different combinations leading to proteinuria, hematuria, and azotemia. Although disease process begins in the cells of mentioned above, there is cross-talk with tubular cells leading to tubular atrophy and interstitial fibrosis in the final stages of most GN. Recent developments in genetic, molecular, serologic methods enhances understanding of the pathophysiology and management of GN although more work is needed. The recent ultra-structural studies demonstrated various subcellular disorders present in the context of GN. Mitochondria are one of the most studied subcellular organelles, and various mitochondrial structural and functional alterations have been identified in GNs, including focal segmental glomerulosclerosis, IgA nephropathy, lupus nephritis and anti-glomerular basement membrane disease. However, these studies are still at an early stage and currently the impacts of mitochondrial dysfunction on the development and progression of glomerular disease are not well defined. In the current review article, we examine how mitochondrial dysfunction associates with GN, and discuss the unknowns, conflicting issues and potential treatment options regarding mitochondrial dysfunction and GN.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145130789","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":"Risk factors for mild cognitive impairment in Parkinson disease: a systematic review and meta-analysis.","authors":"Yaodan Zhang, Fang Chen, Fengchun Ren","doi":"10.1007/s11010-025-05392-y","DOIUrl":"https://doi.org/10.1007/s11010-025-05392-y","url":null,"abstract":"<p><strong>Background: </strong>Mild cognitive impairment (MCI) is a common non-motor manifestation of Parkinson's disease (PD) and often precedes dementia. However, evidence on its demographic and clinical risk factors remains inconsistent. This study aimed to synthesize available data through a meta-analysis to identify determinants of MCI in PD.</p><p><strong>Methodology: </strong>This systematic review and meta-analysis followed PRISMA guidelines. Electronic databases were searched using MeSH terms and validated keywords. Studies were selected through a multi-step screening process by independent reviewers. Data extraction and quality assessment were performed using the Newcastle-Ottawa Scale. Meta-analyses were conducted using Comprehensive Meta-Analysis (v2). Random- or fixed-effects models were applied based on heterogeneity (I² threshold = 50%). Beggs and Mazumdar test assessed publication bias, with significance set at (P < 0.1).</p><p><strong>Results: </strong>This meta-analysis included 33 studies, Significant risk factors for MCI in individuals with PD included older age (effect size = 0.4, 95% CI: 0.315-0.498, P ≤ 0.001), older age at disease onset (effect size = 0.18, 95% CI: 0.05-0.327, P ≤ 0.001), and longer disease duration (effect size = 0.14, 95% CI: 0.08-0.2, P ≤ 0.001). Higher educational attainment showed a protective effect (effect size = -0.438, 95% CI: -0.555 to -0.321, P ≤ 0.001). No significant association was found between gender and MCI (OR = 0.899, 95% CI: 0.749-1.079, P = 0.253). Disease severity, based on UPDRS and Hoehn and Yahr scales, was significantly associated with increased MCI risk.</p><p><strong>Conclusion: </strong>Advanced age, later disease onset, longer disease duration, and greater severity are key risk factors for MCI in PD. These findings highlight the need for early detection and proactive management to guide clinical decisions.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145081079","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: Endothelial dysfunction in cardiovascular diseases: mechanisms and in vitro models.","authors":"Ana Grego, Cristiana Fernandes, Ivo Fonseca, Marina Dias-Neto, Raquel Costa, Adelino Leite-Moreira, Sandra Marisa Oliveira, Fábio Trindade, Rita Nogueira-Ferreira","doi":"10.1007/s11010-025-05390-0","DOIUrl":"https://doi.org/10.1007/s11010-025-05390-0","url":null,"abstract":"","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145081094","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: HIV-1 genome-encoded hiv1-mir-H1 impairs cellular responses to infection.","authors":"Deepak Kaul, A Ahlawat, Sunny Duttagupta","doi":"10.1007/s11010-025-05383-z","DOIUrl":"https://doi.org/10.1007/s11010-025-05383-z","url":null,"abstract":"","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145070066","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 many ways to inhibit translation by Sorafenib in liver cancer cells.","authors":"Laura Contreras, Sara Ricciardi, Stefano Biffo, Jordi Muntané, Jesús de la Cruz","doi":"10.1007/s11010-025-05391-z","DOIUrl":"https://doi.org/10.1007/s11010-025-05391-z","url":null,"abstract":"<p><p>Sorafenib targets various tyrosine kinase receptors, inhibiting cell growth and proliferation, angiogenesis and metastasis in tumour cells. It is used to treat certain types of cancers including renal, thyroid and liver (hepatocellular carcinoma) cancers. Although Sorafenib is approved for advanced hepatocellular carcinoma, it only extends patient´s lives by a few months, highlighting the urgent need to better understand how it works and to develop more effective treatments. Sorafenib specifically inhibits translation initiation in hepatocellular carcinoma cells. Herein, we revealed that this inhibition results, at least, from the activation of PERK, triggering a stress response that leads to eIF2α phosphorylation, the inhibition of MNK1a-signalling-dependent eIF4E phosphorylation, and the aberrant assembly of the canonical eIF4F complex. Sorafenib also inhibits the ERK1/2 MAPK signalling in HepG2 cells. However, the mTORC1 pathway does appear to play a pivotal role in Sorafenib-dependent translation inhibition, as revealed by the phosphorylation levels of RPS6 and 4EBP1 proteins and the effects on translation of gene silencing 4EBP1/2 in Sorafenib-treated cells. Translation inhibition correlates with reduced production of cancer-promoting proteins like Cyclin D1 and c-Myc. Overexpression of the phosphomimetic eIF4E-S209D variant, which constitutively activates eIF4E, shows that inhibition of eIF4E phosphorylation directly causes Cyclin D1 down-regulation and cell-cycle delay in Sorafenib-treated cells. Taken together, our results confirm that Sorafenib induces translation reprogramming, whose understanding is crucial for improving its efficacy as a cancer therapy.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145065064","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}