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Regulatory Mechanism of DHCR7 Gene Expression by Estrogen in Chicken Granulosa Cells of Pre-Hierarchical Follicles. 雌激素对鸡分级前卵泡颗粒细胞DHCR7基因表达的调控机制
IF 4.8 2区 生物学
Biomolecules Pub Date : 2025-05-05 DOI: 10.3390/biom15050668
Dandan Li, Longxiao Hu, Qingqing Wei, Li Kang, Yi Sun, Yunliang Jiang
{"title":"Regulatory Mechanism of <i>DHCR7</i> Gene Expression by Estrogen in Chicken Granulosa Cells of Pre-Hierarchical Follicles.","authors":"Dandan Li, Longxiao Hu, Qingqing Wei, Li Kang, Yi Sun, Yunliang Jiang","doi":"10.3390/biom15050668","DOIUrl":"10.3390/biom15050668","url":null,"abstract":"<p><p>The difference in chicken egg production is closely related to the efficiency of follicle selection, which is marked by granulosa cell differentiation and progesterone production with cholesterol as the substrate. The conversion of 7-dehydrocholesterol to cholesterol catalyzed by 7-Dehydrocholesterol reductase (DHCR7) is the rate-limiting step in cholesterol synthesis. Our previous study revealed that estrogen enhanced the mRNA expression of three <i>DHCR7</i> transcript variants (T1, T3, and T4) in a dose-dependent manner in the granulosa cells of chicken pre-hierarchical follicles (Pre-GCs). This study investigates the molecular mechanisms through which estrogen regulates <i>DHCR7</i> in chicken Pre-GCs. At the transcriptional level, through CUT&RUN-qPCR, we found that under basal conditions, sterol-regulatory element binding protein 2 (SREBP2) bound to the promoters of three <i>DHCR7</i> transcript variants to promote cholesterol synthesis in Pre-GCs to maintain low cholesterol levels; meanwhile upon estrogen treatment, estrogen receptors α and β bound to the regulatory regions of three chicken <i>DHCR7</i> transcript variants, leading to a reduction in the interaction between SREBP2 and <i>DHCR7</i>. At the translational level, the upstream open reading frames (uORFs) and N6-methyladenosine (m<sup>6</sup>A) modification in the 5'UTR of different <i>DHCR7</i> transcripts differentially regulate the expression of T3 and T4, as detected by dual-luciferase reporter assays, but this regulation is not affected by estrogen. This study systematically explores the molecular mechanisms through which estrogen upregulates <i>DHCR7</i> expression in chicken Pre-GCs and provides a clue for understanding the molecular mechanisms underlying cholesterol synthesis in chicken ovarian follicles.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 5","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12108600/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144156462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Racial and Ethnic Disparities in NAFLD: Harnessing Epigenetic and Gut Microbiota Pathways for Targeted Therapeutic Approaches. NAFLD的种族和民族差异:利用表观遗传和肠道微生物群途径进行靶向治疗。
IF 4.8 2区 生物学
Biomolecules Pub Date : 2025-05-05 DOI: 10.3390/biom15050669
Mohamed Zaiou, Olivier Joubert
{"title":"Racial and Ethnic Disparities in NAFLD: Harnessing Epigenetic and Gut Microbiota Pathways for Targeted Therapeutic Approaches.","authors":"Mohamed Zaiou, Olivier Joubert","doi":"10.3390/biom15050669","DOIUrl":"10.3390/biom15050669","url":null,"abstract":"<p><p>Nonalcoholic fatty liver disease (NAFLD) is a growing global health concern, impacting approximately 32.4% of the worldwide population. As a disease linked to metabolic dysfunction, NAFLD continues to rise alongside global increases in obesity, type 2 diabetes mellitus (T2DM), and metabolic syndrome. There is considerable evidence indicating that NAFLD disproportionately affects racial, ethnic, and minority groups, although the exact reasons for these disparities remain elusive. Contributing factors to this disease may include socioeconomic status, cultural influences, stress, genetic factors, and lifestyle choices. Emerging evidence suggests that these causal factors could influence epigenetic mechanisms, particularly DNA methylation and histone modifications, as well as the composition and diversity of gut microbiota. Nevertheless, there is a scarcity of research that comprehensively examines the interplay between epigenetic changes and gut microbiome variations in relation to NAFLD disparities across different racial and ethnic populations globally. This paper intends to (i) explore the connections between NAFLD, ethnic disparities, gut microbiota composition, and epigenetic alterations, while reviewing pertinent studies that illustrate how these factors contribute to health inequities among various ethnic groups impacted by this disease; (ii) explore potential therapeutic targets and biomarkers to advance the management of NAFLD; and (iii) provide insights to enhance our understanding of the mechanisms associated with this disease, thereby promoting further research in this field. Advancements in this area are anticipated to enhance our understanding of disease susceptibilities in at-risk groups and to provide new therapeutic options for NAFLD and its associated complications.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 5","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12109303/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144156351","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Biological Activities of Essential Oils and Hydrolates from Different Parts of Croatian Sea Fennel (Crithmum maritimum L.). 克罗地亚海茴香(Crithmum maritimum L.)不同部位精油和水合物的生物活性。
IF 4.8 2区 生物学
Biomolecules Pub Date : 2025-05-04 DOI: 10.3390/biom15050666
Livia Slišković, Nikolina Režić Mužinić, Olivera Politeo, Petra Brzović, Josip Tomaš, Ivana Generalić Mekinić, Marijana Popović
{"title":"Biological Activities of Essential Oils and Hydrolates from Different Parts of Croatian Sea Fennel (<i>Crithmum maritimum</i> L.).","authors":"Livia Slišković, Nikolina Režić Mužinić, Olivera Politeo, Petra Brzović, Josip Tomaš, Ivana Generalić Mekinić, Marijana Popović","doi":"10.3390/biom15050666","DOIUrl":"10.3390/biom15050666","url":null,"abstract":"<p><p>The traditional nutritional use of sea fennel (<i>Crithmum maritimum</i> L.) has been rediscovered and reestablished, making this halophyte plant a prominent ingredient in coastal cuisine and a subject of interest in various scientific disciplines, including pharmacy and medicine. The first objective of this study was to identify the volatile profiles of essential oils (EOs) and hydrolates derived from the leaves, flowers, and fruits of sea fennel using gas chromatography-mass spectrometry. A total of 25 different volatiles were identified in the EOs and 63 were identified in the hydrolates. Limonene was the most abundant component in the EOs (74.85%, 74.30%, and 67.41%, respectively), while in the hydrolates, it was terpinen-4-ol in the leaves (27.8%) and the flowers (36.7%) and (<i>Z</i>)-carveol in the fruits (11.4%). The second objective was to investigate the biological activities of the samples. The antioxidant and choline inhibitory activities of hydrolates were generally low, with the flower hydrolate providing the inhibition of both enzymes and the leaf hydrolate with the highest antiradical activity. The cytotoxic activities of the EOs and hydrolates were also investigated. The human breast adenocarcinoma cell line MDA-MB-23 was the most sensitive against EOs from the flowers and fruits, reaching the IC<sub>50</sub> after 48 and 72 h, respectively. The leaf hydrolate exhibited cytotoxic activity after 72 h, while the flower hydrolate was effective after 48 h. The MCF-7 cell line was sensitive to the flower and fruit EOs, and the IC<sub>50</sub> was reached at all the tested periods. Overall, the results highlight sea fennel as a rich source of bioactive compounds that have significant potential for greater utilization in the nutraceutical and pharmaceutical industries.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 5","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12108800/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144156576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Recent Advances in Multiple Strategies for the Biosynthesis of Sesquiterpenols. 倍半萜类化合物生物合成的多种策略研究进展。
IF 4.8 2区 生物学
Biomolecules Pub Date : 2025-05-03 DOI: 10.3390/biom15050664
Mengyuan Li, Ruiqi Chen, Jianjun Qiao, Weiguo Li, Hongji Zhu
{"title":"Recent Advances in Multiple Strategies for the Biosynthesis of Sesquiterpenols.","authors":"Mengyuan Li, Ruiqi Chen, Jianjun Qiao, Weiguo Li, Hongji Zhu","doi":"10.3390/biom15050664","DOIUrl":"10.3390/biom15050664","url":null,"abstract":"<p><p>Sesquiterpenols, a class of natural compounds composed of three isoprene units that form a 15-carbon skeleton with hydroxyl (-OH) group, are characterized by their volatility and potent aromatic properties. These compounds exhibit a wide range of biological activities, including antitumor, antibacterial, anti-inflammatory, anti-neurotoxic, antiviral, immunosuppressive, hepatoprotective, and cardiotonic effects. Due to their diverse physiological functionalities, sesquiterpenols serve as critical raw materials in the pharmaceutical, food, and cosmetic industries. In recent years, research on the heterologous synthesis of sesquiterpenol compounds using microbial systems has surged, attracting significant scientific interest. However, challenges such as low yields and high production costs have impeded their industrial-scale application. The rapid development of synthetic biology has introduced innovative methodologies for the microbial production of sesquiterpenol compounds. Herein, we examine the latest synthetic biology strategies and progress in microbial sesquiterpenol production, focusing on adaptive sesquiterpenol synthase screening and expression, synthesis pathway regulation, intracellular compartmentalized expression strategies, and tolerance to terpenoid-related toxicity. Critical challenges and future directions are also discussed to advance research in sesquiterpenol biosynthesis.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 5","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12108891/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144156445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Identification of Critical Molecular Pathways Induced by HDAC11 Overexpression in Cardiac Mesenchymal Stem Cells. 心脏间充质干细胞中HDAC11过表达诱导的关键分子通路的鉴定
IF 4.8 2区 生物学
Biomolecules Pub Date : 2025-05-03 DOI: 10.3390/biom15050662
Chongyu Zhang, Neal L Weintraub, Yaoliang Tang
{"title":"Identification of Critical Molecular Pathways Induced by HDAC11 Overexpression in Cardiac Mesenchymal Stem Cells.","authors":"Chongyu Zhang, Neal L Weintraub, Yaoliang Tang","doi":"10.3390/biom15050662","DOIUrl":"10.3390/biom15050662","url":null,"abstract":"<p><p>HDAC11, the only class IV histone deacetylase, primarily functions as a fatty acid deacylase and has been implicated in metabolic regulation, cancer stemness, and muscle regeneration. However, its role in cardiac mesenchymal stem cells (CMSCs) remains unexplored. To investigate the effects of HDAC11 overexpression on the gene regulatory networks in CMSCs, we treated mouse CMSCs with an adenoviral vector encoding human HDAC11 (Ad-HDAC11) versus adenoviral GFP (Ad-GFP) as a control. Gene expression and pathway enrichment were assessed using RNA sequencing (RNA-seq), and HDAC11 overexpression was validated at the RNA and protein levels through qRT-PCR and Western blot. RNA-seq and Gene Ontology (GO) analysis revealed that HDAC11 overexpression activated cell cycle pathways while suppressing nucleotide transport and phagolysosome-related processes. Furthermore, pHH3 protein level was increased, suggested enhanced proliferation in HDAC11-overexpressed CMSCs. qRT-PCR also confirmed the downregulation of GM11266, a long non-coding RNA, in HDAC11-overexpressing CMSCs. In summary, HDAC11 overexpression promotes transcriptional reprogramming, cell cycle progression, and CMSC proliferation, underscoring its potential role in regulating CMSC growth and division.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 5","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12109384/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144156450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Combination of Periodontal Ligament Stem Cells and Metformin via Organic Cation Transporters for Periodontal Regeneration in Rats. 牙周韧带干细胞与二甲双胍通过有机阳离子转运体联合用于大鼠牙周再生。
IF 4.8 2区 生物学
Biomolecules Pub Date : 2025-05-03 DOI: 10.3390/biom15050663
Qingchen Qiao, Zeqing Zhao, Yaxi Sun, Jing Wang, Xiaowei Li, Li Zhang, Hao Yang, Ning Zhang, Ke Zhang, Yuxing Bai
{"title":"Combination of Periodontal Ligament Stem Cells and Metformin via Organic Cation Transporters for Periodontal Regeneration in Rats.","authors":"Qingchen Qiao, Zeqing Zhao, Yaxi Sun, Jing Wang, Xiaowei Li, Li Zhang, Hao Yang, Ning Zhang, Ke Zhang, Yuxing Bai","doi":"10.3390/biom15050663","DOIUrl":"10.3390/biom15050663","url":null,"abstract":"<p><p>Periodontal regeneration remains challenging due to individual variability, especially in treatments involving bioactive factors such as metformin. This study aimed to investigate the role of organic cation transporters (OCTs) in metformin-induced periodontal regeneration. The expression and function of OCTs in human periodontal ligament stem cells (hPDLSCs) were assessed, and OCT-mediated metformin uptake was quantified by high-performance liquid chromatography (HPLC). Osteogenic and cementogenic differentiation markers were analyzed in vitro, and periodontal regeneration was evaluated using a rat periodontal defect model. OCTs were differentially expressed and functional in hPDLSCs. Both the OCT1 inhibitor cimetidine and OCT1 knockdown significantly reduced intracellular metformin accumulation to 50-60% and 20-30% of control levels, respectively (<i>p</i> < 0.01). Cimetidine diminished the osteogenic and cementogenic effects of metformin by approximately 31-48% and 32-40%, respectively (<i>p</i> < 0.01). In vivo, oral administration of cimetidine decreased bone regeneration by 25% and cementum regeneration by 36% compared with controls receiving GelMA/hPDLSCs/metformin (<i>p</i> < 0.01). This study demonstrates that OCTs regulate metformin uptake in hPDLSCs, and that inhibition of OCT1 by cimetidine significantly reduces the osteogenic and cementogenic efficacy of metformin, providing the first evidence of drug interactions affecting periodontal regeneration mediated by OCT transport in rats.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 5","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12108652/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144156655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Prebiotics and Probiotics Supplementation in Pigs as a Model for Human Gut Health and Disease. 在猪体内添加益生元和益生菌作为人类肠道健康和疾病的模型。
IF 4.8 2区 生物学
Biomolecules Pub Date : 2025-05-03 DOI: 10.3390/biom15050665
Raffaella Rossi, Edda Mainardi
{"title":"Prebiotics and Probiotics Supplementation in Pigs as a Model for Human Gut Health and Disease.","authors":"Raffaella Rossi, Edda Mainardi","doi":"10.3390/biom15050665","DOIUrl":"10.3390/biom15050665","url":null,"abstract":"<p><p>Animal models are an essential part of translational research for the purpose of improving human health. The pig is a potential human research model that can be used to assess the effects of dietary interventions, pathologies, and drugs on gut health and the microbiome, due to its anatomical and physiological similarity to humans. It is recognised that a healthy gut is closely linked to the prevention of several chronic diseases, including obesity, diabetes, gastrointestinal inflammation, as well as neurological and cardiovascular diseases. The use of prebiotics and probiotics plays an important role in maintaining a healthy digestive system, which is responsible for modulating all other body functions. The present review focuses on the applications of prebiotics and probiotics in the pig as an animal model in healthy and diseased conditions, in order to highlight the efficacy of these molecules in the perspective of human health outcomes. The data support the use of prebiotics to improve intestinal health in both healthy and diseased states. In addition, the use of human microbiota-associated (HMA) gnotobiotic pigs provided a good model to study the intestinal and systemic immune response and microbiota composition following probiotic supplementation after a vaccine or virus challenge.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 5","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12109129/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144155851","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Liquid Biopsy-Derived Tumor Biomarkers for Clinical Applications in Glioblastoma. 液体活检衍生的肿瘤生物标志物在胶质母细胞瘤中的临床应用。
IF 4.8 2区 生物学
Biomolecules Pub Date : 2025-05-02 DOI: 10.3390/biom15050658
Bruna Pereira de Lima, Leticia Silva Ferraz, Sylvie Devalle, Helena Lobo Borges
{"title":"Liquid Biopsy-Derived Tumor Biomarkers for Clinical Applications in Glioblastoma.","authors":"Bruna Pereira de Lima, Leticia Silva Ferraz, Sylvie Devalle, Helena Lobo Borges","doi":"10.3390/biom15050658","DOIUrl":"10.3390/biom15050658","url":null,"abstract":"<p><p>Glioblastoma (GBM) is the most aggressive primary brain tumor in adults, characterized by rapid growth and resistance to chemotherapy. Conventional treatments remain largely ineffective, with patient survival averaging around 18 months after diagnosis. Current diagnostic methods rely on invasive tissue biopsies and imaging tests. While traditional biopsies involve extracting tissue samples, their routine use is often limited by surgical risks and the challenge of accessing sensitive brain regions. Liquid biopsy has emerged as a promising noninvasive alternative, analyzing circulating tumor components-such as DNA, RNA, extracellular vesicles, and microRNAs-found in body fluids. This approach enables initial diagnosis and continuous disease monitoring, offering a significant advantage over traditional biopsies, which are impractical for frequent repetition during treatment follow-up. This review highlights recent advances in liquid biopsy-derived biomarkers for the clinical management of GBM. The discussion includes the advantages, limitations, and potential of these biomarkers as tools for early diagnosis and disease monitoring. A narrative review of the literature published over the last decade (2014-2024) was conducted using major health-focused scientific databases. The analysis focuses on evaluating the clinical relevance and applicability of liquid biopsy in GBM, offering insights into its potential as a minimally invasive and effective tool for improving glioblastoma management.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 5","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12108610/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144156557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Distinct Clinical Phenotypes in KIF1A-Associated Neurological Disorders Result from Different Amino Acid Substitutions at the Same Residue in KIF1A. KIF1A相关神经系统疾病的不同临床表型是由于KIF1A相同残基上不同的氨基酸取代所致。
IF 4.8 2区 生物学
Biomolecules Pub Date : 2025-05-02 DOI: 10.3390/biom15050656
Lu Rao, Wenxing Li, Yufeng Shen, Wendy K Chung, Arne Gennerich
{"title":"Distinct Clinical Phenotypes in KIF1A-Associated Neurological Disorders Result from Different Amino Acid Substitutions at the Same Residue in KIF1A.","authors":"Lu Rao, Wenxing Li, Yufeng Shen, Wendy K Chung, Arne Gennerich","doi":"10.3390/biom15050656","DOIUrl":"10.3390/biom15050656","url":null,"abstract":"<p><p>KIF1A is a neuron-specific kinesin motor responsible for intracellular transport along axons. Pathogenic <i>KIF1A</i> mutations cause KIF1A-associated neurological disorders (KAND), a spectrum of severe neurodevelopmental and neurodegenerative conditions. While individual <i>KIF1A</i> mutations have been studied, how different substitutions at the same residue affect motor function and disease progression remains unclear. Here, we systematically examine the molecular and clinical consequences of mutations at three key motor domain residues-R216, R254, and R307-using single-molecule motility assays and genotype-phenotype associations. We find that different substitutions at the same residue produce distinct molecular phenotypes, and that homodimeric mutant motor properties correlate with developmental outcomes. In addition, we present the first analysis of heterodimeric KIF1A motors-mimicking the heterozygous context in patients-and demonstrate that while heterodimers retain substantial motility, their properties are less predictive of clinical severity than homodimers. These results highlight the finely tuned mechanochemical properties of KIF1A and suggest that dysfunctional homodimers may disproportionately drive the diverse clinical phenotypes observed in KAND. By establishing residue-specific genotype-phenotype relationships, this work provides fundamental insights into KAND pathogenesis and informs targeted therapeutic strategies.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 5","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12109325/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144156667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Probiotics as Anti-Tumor Agents: Insights from Female Tumor Cell Culture Studies. 益生菌作为抗肿瘤药物:来自女性肿瘤细胞培养研究的见解。
IF 4.8 2区 生物学
Biomolecules Pub Date : 2025-05-02 DOI: 10.3390/biom15050657
Chiara Giorgi, Francesca Lombardi, Francesca Rosaria Augello, Ylli Alicka, Massimiliano Quintiliani, Skender Topi, Annamaria Cimini, Vanessa Castelli, Michele d'Angelo
{"title":"Probiotics as Anti-Tumor Agents: Insights from Female Tumor Cell Culture Studies.","authors":"Chiara Giorgi, Francesca Lombardi, Francesca Rosaria Augello, Ylli Alicka, Massimiliano Quintiliani, Skender Topi, Annamaria Cimini, Vanessa Castelli, Michele d'Angelo","doi":"10.3390/biom15050657","DOIUrl":"10.3390/biom15050657","url":null,"abstract":"<p><p>Breast and ovarian cancers are among the most prevalent cancers in women. Cancerous cells are characterized by their ability to continuously cycle and migrate, forming metastases. Some probiotic strains have shown anti-tumorigenic effects. This study tested the impact of probiotics on OVCAR-3 and MDA-MB-231 cell lines by analyzing proteins involved in cell cycle regulation (pP53, Cyclin D1, pERK1), cell survival (AKT), and cell migration (RhoA) using Western blotting and scratch wound tests. Results indicated a reduction in these proteins and decreased cell migration velocity post-treatment. These findings suggest that certain probiotic combinations can arrest the cell cycle, promote cell death, and reduce cell migration, potentially serving as promising candidates alongside standard therapies.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 5","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12108976/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144156404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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