BioFactors最新文献

{"title":"Investigating the impact of Ras-related protein RAB7A on colon adenocarcinoma behavior and its clinical significance","authors":"Zhili Shan,&nbsp;Xin Chen,&nbsp;Hong Chen,&nbsp;Xiaojun Zhou","doi":"10.1002/biof.70006","DOIUrl":"https://doi.org/10.1002/biof.70006","url":null,"abstract":"<p>The Ras-related protein RAB7A has been implicated in the development and prognosis of various cancers. This study aims to investigate the prognostic significance of RAB7A in colon adenocarcinoma (COAD). We conducted a retrospective cohort study of COAD cases to assess RAB7A expression and its clinical relevance. The chi-square test was employed to establish associations between clinical features and RAB7A expression. Survival analyses, including Kaplan–Meier and Cox regression, were employed to evaluate the impact of RAB7A expression and clinical characteristics on COAD patient outcomes. Furthermore, we validated our clinical findings using The Cancer Genome Atlas (TCGA) dataset. To elucidate the tumor-related role of RAB7A in COAD, we conducted cellular assays and mouse models. Elevated RAB7A expression in COAD tissues exhibited significant associations with tumor size, invasion depth, and lymph node metastasis (all <i>p</i> &lt; 0.05). Univariate and multivariate analyses revealed that high RAB7A expression was significantly correlated with poorer overall survival. In vitro cellular assays, coupled with knockdown strategies, demonstrated that RAB7A promotes COAD tumor proliferation and invasion, a finding further substantiated by in vivo xenograft experiments. RAB7A may serve as a valuable biomarker and potential therapeutic target in the management of COAD.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"51 1","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143380757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The in vitro and in vivo skin-whitening activity of Ectoine through enhanced autophagy in melanocytes and keratinocytes and zebrafish model","authors":"Wei-Chen Jane,&nbsp;Siang-Jyun Chen,&nbsp;Jhih-Hsuan Hseu,&nbsp;Xuan-Zao Chen,&nbsp;Sudhir Pandey,&nbsp;Hsueh-Wei Chang,&nbsp;Hsin-Ling Yang,&nbsp;You-Cheng Hseu,&nbsp;Yung-Luen Yu","doi":"10.1002/biof.70004","DOIUrl":"https://doi.org/10.1002/biof.70004","url":null,"abstract":"<p>Ectoine, a natural bacterial osmolyte, suppressed UVA irradiated-α-melanocyte stimulating hormone (MSH) stimulated melanogenesis through antioxidant Nrf2 pathways in human keratinocytes; however, the underlying skin whitening mechanisms were not elucidated. The depigmenting efficiency of Ectoine (0–400 μM) through antimelanogenesis and melanin degradation by autophagy promotion was investigated in melanoma (B16F10) and melanin-feeding keratinocyte (HaCaT) cells and in vivo zebrafish model. MTT assay, Western blotting, GFP-LC3 puncta, AVO formation, melanin assay, immunofluorescence staining, TEM techniques, siLC3 transfection, and zebrafish model were utilized. Ectoine-induced autophagy in B16F10 and HaCaT cells was shown by enhanced LC3-II accumulation, autophagosome GFP-LC3 puncta, autolysosome AVOs formation, ATG4B downregulation, and Beclin-1/Bcl-2 dysregulation. The immunoprecipitation data revealed that Ectoine increased the association between LC3-II and p62 proteins in B16F10 and HaCaT cells. Importantly, antioxidant NAC pretreatment antagonized the Ectoine-induced ATG4B diminution in B16F10 and HaCaT cells. Ectoine inhibited melanogenesis by suppressing melanosome gp100, tyrosinase, TRP-1/-2, and/or melanin formation via autophagy in α-MSH-stimulated B16F10 and melanin-feeding HaCaT cells. TEM findings displayed that Ectoine increased melanosome-engulfing autophagosomes and autolysosomes in α-MSH-stimulated B16F10 and melanin-feeding HaCaT cells. Ectoine-inhibited melanogenesis in α-MSH-stimulated B16F10 cells and melanin-feeding HaCaT cells was reversed by pretreatment with the autophagy inhibitor 3-MA or LC3 silencing. In vivo study demonstrated that Ectoine (5 mM) suppressed endogenous body pigmentation by antimelanogenesis and melanin degradation through autophagy induction in a zebrafish model. The in vitro and in vivo study demonstrated that Ectoine inhibits melanogenesis and enhances melanin degradation by triggering autophagy. Ectoine could be utilized as a whitening ingredient in cosmetic formulations.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"51 1","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143186511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Leveraging supramolecular systems in biomedical breakthroughs","authors":"Shreya Maity,&nbsp;Vishal Kumar Deb,&nbsp;Sayani Mondal,&nbsp;Akansha Chakraborty,&nbsp;Kousik Pramanick,&nbsp;Suman Adhikari","doi":"10.1002/biof.70005","DOIUrl":"https://doi.org/10.1002/biof.70005","url":null,"abstract":"<p>Supramolecular systems, intricate assemblies of molecular subunits organized through various intermolecular interactions, offer versatile platforms for diverse applications, including gene therapy, antimicrobial therapy, and cellular engineering. These systems are cost-effective and environmentally friendly, contributing to their attractiveness in biomaterial design. Furthermore, supramolecular biomaterials based on acyclic, macrocyclic compounds and lipid-based assembly offer potential applications in distinct types of biomedical approaches. In this context, they can transport several therapeutic agents very effectively to the target site. Supramolecular hydrogels exhibit potent antimicrobial activity by disrupting microbial membranes, offering promising solutions to combat drug-resistant pathogens. Additionally, supramolecular luminescent nanoparticles enable targeted cell imaging, facilitating disease diagnosis and treatment with high specificity and sensitivity. In cellular engineering, supramolecular assemblies of small molecules demonstrate biological activities, overcoming challenges in cancer treatment by inhibiting signaling pathways and inducing apoptosis in cancer cells. This review emphasizes the applications of supramolecular systems from gene therapy to cellular imaging, tissue engineering, and antimicrobial therapy, showcasing their potential to drive innovation and address pressing healthcare challenges.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"51 1","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143112117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Agmatine suppresses glycolysis via the PI3K/Akt/mTOR/HIF-1α signaling pathway and improves mitochondrial function in microglia exposed to lipopolysaccharide","authors":"Katarina Milosevic,&nbsp;Ana Milosevic,&nbsp;Ivana Stevanovic,&nbsp;Anica Zivkovic,&nbsp;Danijela Laketa,&nbsp;Marija M. Janjic,&nbsp;Ivana Bjelobaba,&nbsp;Irena Lavrnja,&nbsp;Danijela Savic","doi":"10.1002/biof.2149","DOIUrl":"10.1002/biof.2149","url":null,"abstract":"<p>Modulating metabolic pathways in activated microglia can alter their phenotype, which is relevant in uncontrolled neuroinflammation as a component of various neurodegenerative diseases. Here, we investigated how pretreatment with agmatine, an endogenous polyamine, affects metabolic changes in an in vitro model of neuroinflammation, a murine microglial BV-2 cell line exposed to lipopolysaccharide (LPS). Hence, we analyzed gene expression using qPCR and protein levels using Western blot and ELISA. Microglial metabolic status was assessed by measuring lactate release and cellular ATP by enzymatic and luminescence spectrophotometry. Mitochondrial functionality was analyzed by fluorescent probes detecting mitochondrial membrane potential (mtMP) and superoxide production. Our findings suggest that kinase pathways associated with hypoxia-inducible factor-1α (HIF-1α) regulate energy metabolism in pro-inflammatory activated microglia. We have shown that LPS induces HIF-1α and genes for glucose transporter and glycolytic rate, increases lactate production and causes mitochondrial dysfunction, suggesting a metabolic shift towards glycolysis. Agmatine inhibits the PI3K/Akt pathway and negatively regulates mammalian target of rapamycin (mTOR) phosphorylation and HIF-1α levels, reducing lactate and tumor necrosis factor (TNF) production, which is supported by pharmacological blockade of PI3K. Pretreatment with agmatine also rescues mitochondrial function by counteracting the LPS-induced decline in mtMP and increase in mitochondrial superoxide, resulting in an anti-apoptotic effect. Agmatine alone increases intracellular ATP levels and maintains this effect even under pro-inflammatory conditions. Our study emphasizes the ability of agmatine to engage in metabolic reprogramming of pro-inflammatory microglia through increased ATP production and modulation of signaling pathway involved in promoting glycolysis and cytokine release.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"51 1","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11780571/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143063274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Control of Mycobacterium tuberculosis infection in the elderly: Is there a role for epigenetic reprogramming reversal?","authors":"Dámaris P. Romero-Rodríguez,&nbsp;Carlos A. Díaz-Alvarado,&nbsp;Héctor Isaac Rocha-González,&nbsp;Esmeralda Juárez","doi":"10.1002/biof.2151","DOIUrl":"10.1002/biof.2151","url":null,"abstract":"<p>With the increase in the elderly population worldwide, the number of subjects suffering from tuberculosis (TB) has shown an increased prevalence in this group. Immunosenescence is essential in this phenomenon because it may reactivate the lesions and render their adaptive immunity dysfunctional. In addition, inflammation in the lungs of the elderly subjects is also dysfunctional. Although effective drugs are available, they are often tolerated inadequately, reducing adherence to the therapy and leading to therapeutic failure. Comorbidities, poor general health status, and other medications may lead to increased drug adverse reactions and reduced adherence to treatment in the elderly. Hence, older adults require an individualized approach for better outcomes. Trained immunity, which involves epigenetic reprogramming, may contribute to balancing the dysfunction of innate and adaptive immunity in older people. This review analyzes the relationship between inflammation, age, and <i>Mycobacterium tuberculosis</i>. Moreover, we hypothesize that immunomodulation using trained immunity activators will help reduce inflammation while enhancing antimicrobial responses in the elderly. Understanding immunomodulation's molecular and physiological effects will lead to informed decisions about TB prevention and treatment strategies uniquely designed for the elderly.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"51 1","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143063275","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Untargeted metabolomics reveals biomarkers for the diagnosis of coronary artery plaques as observed by coronary cardiac computed tomography","authors":"Manar Shmet,&nbsp;Mansor Amasha,&nbsp;Ali Khattib,&nbsp;Ron Schweitzer,&nbsp;Saeed Khatib,&nbsp;Jihad Hamudi,&nbsp;Majdi Halabi,&nbsp;Soliman Khatib","doi":"10.1002/biof.2156","DOIUrl":"10.1002/biof.2156","url":null,"abstract":"<p>Atherosclerosis is a major cause of morbidity and mortality worldwide; in Israel, ischemic heart disease is the second leading cause of death for both genders aged 45 and above. Atherosclerosis involves stiffening of the arteries due to the accumulation of lipids and oxidized lipids on the blood vessel walls, triggering the development of artery plaque. Coronary artery disease (CAD) is the most common manifestation of atherosclerosis. The prevalence of CAD in the general population remains high, despite efforts to improve the identification of risk factors and preventive treatments. The discovery of new biomarkers is vital to improving the diagnosis of CAD and its risk factors. We aimed to identify novel biomarkers that could provide an early diagnosis of coronary artery atherosclerotic plaques, their type, and the percentage of stenosis. We used an untargeted metabolomics approach to identify potential biomarkers that could enable highly sensitive and specific CAD detection. The study consisted of 109 patients who underwent cardiac computed tomography angiography at the Cardiology Department of Ziv Medical Center. Fifty-four patients were diagnosed with coronary atherosclerotic plaques (CAD group), and 55 without plaques used control. Untargeted metabolomics using LC–MS/MS revealed 2560 metabolites in the patients' serum: 106 showed statistically significant upregulation in the serum of the CAD group compared with the healthy control group (<i>p</i> &lt; 0.05). These metabolites belonged to the following chemical families: acyl-carnitines, cyclodipeptides, lysophosphatidylcholine, and primary bile acids. In contrast, 98 metabolites displayed statistically significant downregulation in the serum of the CAD group compared with the control group, belonging to the following chemical families: GABA amino acids and derivatives (inhibitory neurotransmitters), lipids, and secondary bile acids. Our comprehensive untargeted serum metabolomic analysis revealed biomarkers that can be used for the diagnosis of patients with CAD. Further cohort studies with a larger number of participants are needed to validate the detected biomarkers.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"51 1","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143057954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vitamin D modulates the content of inflammatory microRNAs in extracellular vesicles from human adipocyte cells in inflammatory context","authors":"Thomas Payet,&nbsp;Julien Astier,&nbsp;Lorrine Bournot,&nbsp;Flavie Sicard,&nbsp;Stéphane Robert,&nbsp;Romaric Lacroix,&nbsp;Martin Wabitsch,&nbsp;Jean-François Landrier,&nbsp;Lourdes Mounien","doi":"10.1002/biof.70003","DOIUrl":"10.1002/biof.70003","url":null,"abstract":"<p>Inflammation of adipose tissue is a contributing factor to many chronic diseases associated with obesity. We previously showed that micronutrients such as vitamin D (VD) limited this metabolic inflammation by decreasing inflammatory markers expression including miR-155 (microRNA-155) or miR-146a in different in vitro and in vivo models. These miRNAs could be incorporated into extracellular vesicles (EVs) in order to modulate the activity of target cells. Nevertheless, the role of VD on the miRNAs contained in EVs from adipose tissue in inflammatory conditions remains unclear. In this study, we used a human model of SGBS (Simpson-Golabi-Behmel syndrome) adipocytes preincubated with 1,25(OH)₂D (the active form of VD) before an inflammatory stress with tumor necrosis factor α (TNFα). First, we confirmed by quantitative PCR that the expression of classical inflammatory factors (TNFα and chemokine ligand 2 [CCL2/MCP1]), miR-146a, and miR-155 was increased significantly under inflammatory conditions in SGBS cells and that VD prevented this up-regulation. Secondly, transmission electron microscope imaging of EVs preparations in supernatant allowed visualization of small and large vesicles under these conditions. Then, EVs were obtained with isolation kit and the expression of miR-155 and miR-146a were measured. The expression of miR-155 under TNFα effect was increased in EVs while miR-146a was not detected. Moreover, we also showed that the TNFα-mediated expression of miR-155 in EVs was significantly reduced by a VD pre-incubation of cells. Using miRNA PCR array, we also identified 33 miRNAs, organized in 5 clusters that were differentially regulated by TNFα and VD. Bioinformatic analysis of biological pathways revealed that the different miRNAs targeting genes that are involved in important cell process such as the regulation of transcription or protein phosphorylation. In conclusion, these results support for the first time that VD modulated the expression of miRNAs in EVs from adipocytes, which could represent a new mechanism of regulation of inflammation by micronutrients.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"51 1","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11779547/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143063276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lobaric acid suppresses the stemness potential of colorectal cancer cells through mTOR/AKT","authors":"Sultan Pulat,&nbsp;Jaycee Augusto Gumiran Paguiri,&nbsp;Chathurika D. B. Gamage,&nbsp;Mücahit Varlı,&nbsp;Rui Zhou,&nbsp;So-Yeon Park,&nbsp;Jae-Seoun Hur,&nbsp;Hangun Kim","doi":"10.1002/biof.70002","DOIUrl":"10.1002/biof.70002","url":null,"abstract":"<p><i>Stereocaulon alpinum</i> has been found to have potential pharmaceutical properties due to the presence of secondary metabolites such as usnic acid, atranorin, and lobaric acid (LA) which have anticancer activity. On the other hand, the effect of LA on the stemness potential of colorectal cancer (CRC) cells remains unexplored, and has not yet been thoroughly investigated. In this study, we examined the inhibitory activity of LA from <i>Stereocaulon alpinum</i> against the stemness potential of CRC cells and investigated the possible underlying mechanisms. The results demonstrated that LA did not inhibit the cell viability of CSC221 and DLD1. In addition, LA significantly decreased the spheroid formation of CSC221 and DLD1. Moreover, LA treatment suppressed cancer stem cell (CSC) markers; aldehyde dehydrogenase 1 (ALDH1), B-cell-specific Moloney leukemia virus insertion site 1 (BMI1), musashi1 (MSI1), and leucine-rich repeat-containing G-protein coupled receptor 5 (Lgr5), along with the sonic hedgehog (Shh) and mTOR/AKT pathways that contribute significantly to maintaining the stemness of CRC cells. Therefore, LA may be a new therapeutic approach for reducing the stemness of CRC cells.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"51 1","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143057952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Involvement of metformin and aging in salivary expression of ACE2 and TMPRSS2","authors":"Yosuke Shikama,&nbsp;Kunihiro Otsuka,&nbsp;Yuka Shikama,&nbsp;Masae Furukawa,&nbsp;Naozumi Ishimaru,&nbsp;Kenji Matsushita","doi":"10.1002/biof.2154","DOIUrl":"10.1002/biof.2154","url":null,"abstract":"<p>SARS-CoV-2-related proteins, ACE2 and TMPRSS2, are determinants of SARS-CoV-2 infection. Although these proteins are expressed in oral-related tissues, their expression patterns and modulatory mechanisms in the salivary glands remain unknown. We herein showed that full-length ACE2, which has both a fully functional enzyme catalytic site and high-affinity SARS-CoV-2 spike S1-binding sites, was more highly expressed in salivary glands than in oral mucosal epithelial cells and the lungs. Regarding TMPRSS2, zymogen and the cleaved form were both expressed in the salivary glands, whereas only zymogen was expressed in murine lacrimal glands and the lungs. Metformin, an AMPK activator, increased stimulated saliva secretion and full-length ACE2 expression and decreased cleaved TMPRSS2 expression in the salivary glands, and exerted the same effects on soluble ACE2 (sACE2) and sTMPRSS2 in saliva. Moreover, metformin decreased the expression of beta-galactosidase, a senescence marker, and ADAM17, a sheddase of ACE2 to sACE2, in the salivary glands. In aged mice, the expression of ACE2 was decreased in the salivary glands, whereas that of sACE2 was increased in saliva, presumably by the up-regulated expression of ADAM17. The expression of TMPRSS2 in the salivary glands and sTMPRSS2 in saliva were both increased. Collectively, these results suggest that the protein expression patterns of ACE2 and TMPRSS2 in the salivary glands differ from those in other oral-related cells and tissues, and also that metformin and aging affect the salivary expression of ACE2 and TMPRSS2, which have the potential as targets for preventing the transmission of SARS-CoV-2.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"51 1","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11771682/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Harnessing the ubiquitin proteasome system as a key player in stem cell biology","authors":"Hind Atta,&nbsp;Dina H. Kassem,&nbsp;Mohamed M. Kamal,&nbsp;Nadia M. Hamdy","doi":"10.1002/biof.2157","DOIUrl":"10.1002/biof.2157","url":null,"abstract":"<p>Intracellular proteins take part in almost every body function; thus, protein homeostasis is of utmost importance. The ubiquitin proteasome system (UPS) has a fundamental role in protein homeostasis. Its main role is to selectively eradicate impaired or misfolded proteins, thus halting any damage that could arise from the accumulation of these malfunctioning proteins. Proteasomes have a critical role in controlling protein homeostasis in all cell types, including stem cells. We will discuss the role of UPS enzymes as well as the 26S proteasome complex in stem cell biology from several angles. First, we shall overview common trends of proteasomal activity and gene expression of different proteasomal subunits and UPS enzymes upon passaging and differentiation of stem cells toward various cell lineages. Second, we shall explore the effect of modulating proteasomal activity in stem cells and navigate through the interrelation between proteasomes' activity and various proteasome-related transcription factors. Third, we will shed light on curated microRNAs and long non-coding RNAs using various bioinformatics tools that might have a possible role in regulating UPS in stem cells and possibly, upon manipulation, can enhance the differentiation process into different lineages and/or delay senescence upon cell passaging. This will help to decipher the role played by individual UPS enzymes and subunits as well as various interrelated molecular mediators in stem cells' maintenance and/or differentiation and open new avenues in stem cell research. This can ultimately provide a leap toward developing novel therapeutic interventions related to proteasome dysregulation.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"51 1","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143021745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}