Molecular and Cellular Biochemistry最新文献

{"title":"HuD and alpha-crystallin A axis protects neuro-retinal cells in early diabetes.","authors":"Chongtae Kim, Subeen Oh, Young-Hoon Park","doi":"10.1007/s11010-025-05364-2","DOIUrl":"https://doi.org/10.1007/s11010-025-05364-2","url":null,"abstract":"<p><p>Diabetic retinopathy (DR) is a prevalent microvascular complication of diabetes; however, neuro-retinal degeneration is also observed in patients with diabetes without signs of DR. The mechanisms leading to neuro-retinal cell loss before vascular complications manifest in diabetes remain poorly understood. In this study, we investigated the neuronal RNA-binding protein HuD as a novel regulator of neuro-retinal degeneration in the early stage of diabetes. We determined the expression of HuD and alpha-crystallin A (CRYAA) in the retinal ganglion cell layer. HuD and CRYAA were down-regulated in the retinas of streptozotocin-induced diabetic rats and in neuro-retinal cells (R-28) treated with high glucose. Cryaa mRNA was identified as a novel target transcript of HuD, and we demonstrated that HuD post-transcriptionally regulates the expression of Cryaa mRNA by binding to its 3'-untranslated region. Silencing and overexpression of HuD positively regulated the expressions of Cryaa mRNA and protein. We demonstrated that the increase in inflammatory cytokines such as TNFα, IL-1β, and IL-6 in R-28 cells under hyperglycemic conditions was a result of both CRYAA and HuD levels. Silencing HuD and CRYAA enhanced high glucose-induced R-28 cell death, whereas their overexpression alleviated this effect. HuD post-transcriptionally regulates CRYAA expression, influencing the function and viability of neuro-retinal cells under diabetic conditions. Our results suggest that the HuD/CRYAA axis plays a crucial role in neuro-retinal cells and has the potential to serve as a prognostic factor and therapeutic target for diabetic neuro-retinal degeneration.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144822018","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":"PACS2/PKCα/NOX4 pathway damaged the renal vascular endothelial barrier by promoting ROS production in diabetic nephropathy mice.","authors":"Xinru Zheng, Qianjun Zhu, Jie Ouyang, Jing Zhang, Quanjun Liu, Jianing Fan, Peng Gao, Haijiao Long, Hong Xiang, Hongwei Lu","doi":"10.1007/s11010-025-05363-3","DOIUrl":"https://doi.org/10.1007/s11010-025-05363-3","url":null,"abstract":"<p><p>Renal vascular endothelial barrier dysfunction plays an important role in the pathogenesis of diabetic nephropathy (DN). Reactive oxygen species (ROS) contribute to barrier dysfunction in various aspects of diabetes. Phosphofurin acidic cluster sorting protein 2 (PACS2) is related to the ROS production, but the specific signaling pathway in endothelial cells remains unclear. In this study, we explored the mechanistic function of PACS2 and its downstream PKCα/NOX4 signaling pathway in endothelial barrier damage in DN. A significant upregulation of PACS2 expression was observed in human umbilical vein endothelial cells treated with high glucose and palmitic acid and glomerular endothelial cells derived from STZ + HFD-induced DN mice. SiRNA-mediated silencing or knockdown of PACS2 reversed the impaired vascular barrier function in vivo and in vitro. Furthermore, the inhibition of PACS2 significantly downregulated the protein expression of PKCα and NOX4 protein and the production of ROS in endothelial cells. Collectively, our findings indicate that the PACS2/PKCα/NOX4 signaling pathway may participate in the pathogenesis of DN by regulating vascular endothelial barrier function.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144799645","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":"Licochalcone A inhibits glioma migration, invasion, and growth by triggering mitochondrial dysfunction and ROS-mediated oxidative damage.","authors":"Chao Yu, Deyan Yang, Nannan Li, Xiaotong Feng, Qile Song, Fusen Zhang, Yuyang Fu, Ping Li","doi":"10.1007/s11010-025-05367-z","DOIUrl":"10.1007/s11010-025-05367-z","url":null,"abstract":"<p><p>Glioma is a common malignant tumor in nervous system, but the treatment efficacy is still unsatisfactory. Licochalcone A (Lic-A) is a kind of flavonoid isolated from glycyrrhiza and shows anti-tumor effect. This study aimed to investigate anti-tumor efficacy of Lic-A on glioma using both in vivo and in vitro models. The in vitro results showed that Lic-A inhibited the growth, migration, and invasion of glioma cells in a dose-dependent way. Lic-A induced mitochondrial dysfunction by regulating Bcl-2 family and induced reactive oxygen species (ROS), while ROS inhibition enhanced the migration and invasion of glioma cells. Finally, animal experiments confirmed that Lic-A inhibited the growth of glioma in vivo. In conclusion, our results suggest that Lic-A can inhibit the migration and invasion of glioma cells while inducing apoptosis of glioma cells. The mechanism may be related to the activation of ATM/ATR pathway and the induction of oxidative stress.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144789577","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":"A review on the epigenetic regulation of testosterone synthesis in Leydig cells.","authors":"Haoran Xu, Jing Zhao, Wenfa Lyu, Jun Wang","doi":"10.1007/s11010-025-05366-0","DOIUrl":"https://doi.org/10.1007/s11010-025-05366-0","url":null,"abstract":"<p><p>Epigenetics studies heritable changes in gene expression without altering the DNA sequence and is involved in diverse biological processes. In male reproduction, Leydig cells, the main site of testosterone synthesis, play an important role in maintaining the reproductive process. However, the role of epigenetics in the mechanism of testosterone synthesis in Leydig cells is still not well understood. This review systematically describes how classic epigenetic modifications such as DNA methylation, RNA methylation, histone modification, and non-coding RNA regulate the testosterone synthesis process of Leydig cells in different species. Accumulating evidences revealed that epigenetics can regulate the process of testosterone synthesis in Leydig cells. In future, we aim to provide new ideas for male reproduction by investigating the relationship between testosterone synthesis mechanisms and epigenetics.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144789576","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":"Targeted delivery aspects of proanthocyanidins in breast cancer treatment: from discovery to development.","authors":"Krishna Kuna, Seshadri Nalla, Jailani Shiekmydeen, Pavan C Akkiraju, Mahesh P More, Srinivas Ganta, Srinivas Enaganti, Rahul S Tade","doi":"10.1007/s11010-025-05365-1","DOIUrl":"https://doi.org/10.1007/s11010-025-05365-1","url":null,"abstract":"<p><p>Proanthocyanidins (PACs), a group of naturally occurring polyphenolic compounds found in a variety of fruits, vegetables, nuts, and seeds, have shown remarkable potential in the treatment of breast cancer (BC). These bioactive molecules exhibit antioxidant, anti-inflammatory, and anticancer properties by triggering apoptosis, halting cell cycle progression, and suppressing angiogenesis and metastasis. PACs further contribute to immune modulation and regulate critical signaling pathways like PI3K/Akt and MAPK, which are closely linked to cancer development. When combined with other bioactive agents, PACs have been shown to enhance therapeutic efficacy. Advanced delivery approaches, including PAC conjugation with targeting molecules and natural biopolymers, such as proteins and polysaccharides, are being explored to improve their effectiveness. Despite increasing interest in the anticancer potential of PACs, a comprehensive analysis of their molecular mechanisms, synergistic effects, and formulation strategies specifically in the context of breast cancer is lacking. This review aims to fill that gap by compiling and critically evaluating current preclinical evidence, novel delivery approaches, and safety considerations related to PACs in breast cancer therapy. Although preclinical investigations provide encouraging evidence, the availability of clinical studies remains scarce, emphasizing the need for further exploration. The discussion also encompasses the safety profile and possible toxicological concerns of PACs, underlining their therapeutic potential and existing challenges. Despite current limitations, PACs hold promise for BC treatment, with future research aiming to refine their clinical applicability.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144784786","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":"AMPK/mTOR balance during exercise: implications for insulin resistance in aging muscle.","authors":"Xie Mingzheng, Weng You","doi":"10.1007/s11010-025-05362-4","DOIUrl":"https://doi.org/10.1007/s11010-025-05362-4","url":null,"abstract":"<p><p>Age-related reductions in skeletal muscle insulin responsiveness promote metabolic dysregulation and contribute to an elevated probability of type 2 diabetes onset. The malfunction of nutrient-responsive signaling routes, specifically AMP-activated protein kinase (AMPK) and mechanistic target of rapamycin (mTOR), constitutes a central component of this biological process. The integrated activity of these kinases in controlling energy dynamics, protein formation, and glucose processing is fundamental to ensure metabolic homeostasis in skeletal muscle tissue. Through its modulation of AMPK and mTOR pathways, exercise helps reinstate signaling equilibrium and supports better insulin efficacy in aging skeletal muscle. This review explores the molecular mechanisms by which different forms of exercise-endurance, resistance, and combined training-modulate the AMPK/mTOR axis in aging muscle. This analysis focuses on exercise-induced AMPK signaling as a catalyst for mitochondrial development, enhanced glucose processing, and intensified fatty acid breakdown, while also temporally coordinating mTOR activity to support muscle maintenance without exacerbating insulin resistance. By integrating insights from aging biology, exercise physiology, and molecular metabolism, this review highlights the therapeutic potential of targeting AMPK/mTOR signaling through physical activity to combat insulin resistance in the elderly.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144784785","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 disease management through phytochemical interventions.","authors":"R Prabhu Ramya, K B Megha, S Reshma, M J Ajai Krishnan, S Amir, Rashmi Sharma, P V Mohanan","doi":"10.1007/s11010-025-05360-6","DOIUrl":"https://doi.org/10.1007/s11010-025-05360-6","url":null,"abstract":"<p><p>Mitochondrial diseases are a diverse group of disorders caused by dysfunction in mitochondria, the energy-generating organelles of cells. These disorders result from mutations in either nuclear or mitochondrial DNA and can be classified as primary (genetic origin) or secondary (environmentally induced). Due to their systemic impact, mitochondrial dysfunction leads to a wide range of clinical symptoms varying from tissue type and patient age. This review aims to provide a comprehensive overview of mitochondrial diseases, focusing on their classification, pathophysiology, diagnostic challenges and emerging therapeutic strategies. Current diagnostic approaches face limitations due to the complexity and heterogeneity of mitochondrial disorders. Recent evidence highlights the potential of phytochemicals such as polyphenols, flavonoids, alkaloids and terpenoids in modulating mitochondrial function. These natural compounds can enhance mitochondrial biogenesis, reduce oxidative stress and improve cellular energy metabolism. Phytochemicals represent a promising therapeutic avenue for mitigating mitochondrial dysfunction. However, further research is needed to validate their efficacy and develop standardized treatment protocols. An improved understanding of the molecular mechanisms involved in mitochondrial pathology will aid in developing more targeted diagnostic and therapeutic strategies.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144775793","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":"Nitric oxide induces apoptosis of human primary melanocytes by regulating calcium homeostasis via VDAC1.","authors":"Jiawei Lu, Yifei Feng, Yidan Wang, Yongkai Yu, Wene Zhao, Xuechen Cao, Ziyu Li, Yan Lu","doi":"10.1007/s11010-025-05361-5","DOIUrl":"https://doi.org/10.1007/s11010-025-05361-5","url":null,"abstract":"<p><p>Vitiligo is an autoimmune skin disease that originates from damage and loss of melanocytes (MCs). Studies have identified abnormal nitric oxide (NO) metabolism in vitiligo patients, but the mechanisms by which NO contributes to MC loss remain unclear. Skin samples from patients with vitiligo and healthy controls were collected to evaluate the expression of three nitric oxide synthases (NOS) isoforms. Keratinocytes, MCs, and fibroblasts were exposed to a cytokine cocktail (IFN-γ, TNF-α, IL-1β and LPS) to simulate the pro-inflammatory microenvironment of vitiligo. Then NOS activation and the capacity for NO production were examined in each cell type. Sodium nitroprusside (SNP) was used as the NO donor to evaluate its cytotoxic effects on MCs. Cell viability, trypan blue staining rate, and lactate dehydrogenase release were measured following SNP exposure. Ultrastructural changes in MCs were observed using transmission electron microscopy. Apoptosis rate, intracellular calcium concentration, and mitochondrial membrane potential were assessed using flow cytometry. BAPTA-AM was used for intracellular calcium chelation and small interfering RNA was used to silence VDAC1 expression in MCs. Inducible NOS (iNOS) expression was significantly upregulated in patients in the active vitiligo lesions. Under pro-inflammatory conditions, keratinocytes and fibroblasts produced increased NO via iNOS activation. MCs exposed to a high-NO environment displayed dose-dependent cellular damage. SNP-treated MCs showed ultrastructural features of apoptosis, including condensed nuclear chromatin and swollen mitochondria. Flow cytometry and analysis of pro-apoptotic markers confirmed mitochondrial-mediated apoptosis in MCs. Both calcium chelation and VDAC1 silencing alleviated the apoptosis of MCs by restoring calcium homeostasis and mitochondrial membrane potential. NO-induced apoptosis in MCs was mediated by calcium overload and mitochondrial dysfunction. iNOS activation may represent a contributor to melanocyte loss in vitiligo and a potential therapeutic target.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144768787","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 gut microbiota-NLRP3 inflammasome connection: current evidence and perspectives for non-communicable diseases.","authors":"Denise Mafra, Livia Alvarenga, Patricia Coelho de Velasco, Larissa de Mattos Manhães, Ludmilla Dias de Santana E Santana, Natalia Alvarenga Borges","doi":"10.1007/s11010-025-05359-z","DOIUrl":"https://doi.org/10.1007/s11010-025-05359-z","url":null,"abstract":"<p><p>Inflammasomes are cytoplasmic multiprotein complexes belonging to the innate immune system, playing a crucial role in responses to microbial infections and controlling mucosal immune responses and metabolic activities. The Nod-Like Pyrin Receptor Domain 3 (NLRP3) inflammasome is one of the most studied and may be a key element in the relationship between gut microbiota and systemic inflammation. Chronic non-communicable diseases have been closely associated with alterations in the gut microbiota (dysbiosis) and the activation of the inflammasome complex. Dysbiosis can expose the host to pathogenic microorganisms and their metabolites, thus triggering immune and inflammatory responses. This review discusses the importance of addressing the interaction between the gut microbiota and the NLRP3 inflammasome pathway and its possible effects on human health. Modulation of the intestinal microbiota may be a crucial factor in preventing and mitigating inflammation, and the NLRP3 inflammasome pathway appears to be substantially involved in this process.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144775804","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":"Effect of metabotropic glutamate receptor 6 on cell morphology and melanosome transfer in melanocytes.","authors":"Jing Ni, Guangming Zhao, Yuejian Liu, Yi Yang, Zhiqi Song","doi":"10.1007/s11010-025-05287-y","DOIUrl":"10.1007/s11010-025-05287-y","url":null,"abstract":"<p><p>The melanosome transfer pathway from melanocytes to keratinocytes has been extensively investigated; however, the underlying molecular mechanisms remain unclear. Therefore, the function of metabotropic glutamate receptor 6 (mGluR6) in the control of melanocyte-to-keratinocyte melanosome transfer, intracellular calcium levels in melanocytes, and the formation of filopodia were explored in this study. Primary melanocytes and keratinocytes were isolated from human foreskin samples. mGluR6 expression was suppressed using lentiviral-mediated short hairpin RNA (shRNA). Scanning electron microscopy (SEM), confocal laser scanning microscopy (CLSM), flow cytometry, and western blot analyses were used to assess filopodia formation, cytoskeletal organization, and melanosome transfer. We found that melanocytes expressed mGluR6 and that mGluR6 knockdown influenced the establishment of dendritic formation, melanocyte filopodia, and microphthalmia-associated transcription factors. Similarly, the efficiency of melanosome transfer from melanocytes to keratinocytes was reduced. According to these findings, melanosome transfer between melanocytes and keratinocytes mostly occurs by filopodia delivery, and mGluR6 directly influences melanosome transfer by altering melanocyte morphology. Comprehensive knowledge of melanosome transfer is essential when developing therapies for skin illnesses characterized by hyperpigmentation or hypopigmentation.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"4873-4882"},"PeriodicalIF":3.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144013122","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}