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Maternal Overnutrition in Beef Cattle: Effects on Fetal Programming, Metabolic Health, and Postnatal Outcomes. 肉牛母体营养过剩:对胎儿编程、代谢健康和产后结局的影响。
IF 3.6 3区 生物学
Biology-Basel Pub Date : 2025-06-02 DOI: 10.3390/biology14060645
Borhan Shokrollahi, Myungsun Park, Gi-Suk Jang, Shil Jin, Sung-Jin Moon, Kyung-Hwan Um, Sun-Sik Jang, Youl-Chang Baek
{"title":"Maternal Overnutrition in Beef Cattle: Effects on Fetal Programming, Metabolic Health, and Postnatal Outcomes.","authors":"Borhan Shokrollahi, Myungsun Park, Gi-Suk Jang, Shil Jin, Sung-Jin Moon, Kyung-Hwan Um, Sun-Sik Jang, Youl-Chang Baek","doi":"10.3390/biology14060645","DOIUrl":"10.3390/biology14060645","url":null,"abstract":"<p><p>Maternal overnutrition and targeted supplements during pregnancy strongly affect fetal development in beef cattle, influencing gene expression, tissue development, and productivity after birth. As modern feeding practices often result in cows receiving energy and protein above requirements, understanding the balance between adequate nutrition and overconditioning is critical for sustainable beef production. This review synthesizes findings from recent studies on maternal overnutrition and supplementation, focusing on macronutrients (energy, protein, methionine) and key micronutrients (e.g., selenium, zinc). It evaluates the timing and impact of supplementation during different gestational stages, with emphasis on fetal muscle and adipose tissue development, immune function, and metabolic programming. The role of epigenetic mechanisms, such as DNA methylation and non-coding RNAs, is also discussed in relation to maternal dietary inputs. Mid-gestation supplementation promotes muscle growth by activating muscle-specific genes, whereas late-gestation diets enhance marbling and carcass traits. However, maternal overnutrition may impair mitochondrial efficiency, encourage fat deposition over muscle, and promote collagen synthesis, reducing meat tenderness. Recent evidence highlights sex-specific fetal programming differences, the significant impact of maternal diets on offspring gut microbiomes, and breed-specific nutritional responses, and multi-OMICs integration reveals metabolic reprogramming mechanisms. Targeted trace mineral and methionine supplementation enhance antioxidant capacity, immune function, and reproductive performance. Precision feeding strategies aligned with gestational requirements improve feed efficiency and minimize overfeeding risks. Early interventions, including protein and vitamin supplementation, optimize placental function and fetal development, supporting stronger postnatal growth, immunity, and fertility. Balancing nutritional adequacy without excessive feeding supports animal welfare, profitability, and sustainability in beef cattle systems.</p>","PeriodicalId":48624,"journal":{"name":"Biology-Basel","volume":"14 6","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12190084/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144498715","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}
引用次数: 0
Research Progress on the Interaction Between SIRT1 and Mitochondrial Biochemistry in the Aging of the Reproductive System. 生殖系统衰老过程中SIRT1与线粒体生物化学相互作用的研究进展
IF 3.6 3区 生物学
Biology-Basel Pub Date : 2025-06-02 DOI: 10.3390/biology14060643
Yang Li, Kai Kang, Huimingda Bao, Siqi Liu, Bangyi Zhao, Guangdong Hu, Jiang Wu
{"title":"Research Progress on the Interaction Between SIRT1 and Mitochondrial Biochemistry in the Aging of the Reproductive System.","authors":"Yang Li, Kai Kang, Huimingda Bao, Siqi Liu, Bangyi Zhao, Guangdong Hu, Jiang Wu","doi":"10.3390/biology14060643","DOIUrl":"10.3390/biology14060643","url":null,"abstract":"<p><p>The protein associated with the silencing information regulator 2-associated enzyme1 (SIRT1) is a highly conserved nicotinamide adenine dinucleotide (NAD<sup>+</sup>)-dependent deacetylase and a key member of the sirtuin family. SIRT1 plays an essential role in various cellular physiological processes, primarily localized in the nucleus but also active in the cytoplasm and mitochondria. Recent studies have demonstrated its capacity to delay aging in multiple organs and tissues, although its underlying mechanisms remain incompletely understood. Additionally, SIRT1 exerts a significant influence on metabolic regulation and genetic processes. As the primary source of cellular energy, mitochondria are central to numerous biological functions. Mitochondrial dysfunction has been implicated in the onset and progression of various diseases and is increasingly recognized for its role in aging-related processes. This article investigates the interaction between SIRT1 and mitochondria in regulating reproductive system aging and elucidates their potential mechanisms of action, providing insights for clinical research into reproductive system aging.</p>","PeriodicalId":48624,"journal":{"name":"Biology-Basel","volume":"14 6","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12189226/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144498696","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}
引用次数: 0
Fermentation Products Originated from Bacillus subtilis Promote Hepatic-Intestinal Health in Largemouth Bass, Micropterus salmoides. 枯草芽孢杆菌发酵产物促进大口黑鲈肝肠健康。
IF 3.6 3区 生物学
Biology-Basel Pub Date : 2025-06-02 DOI: 10.3390/biology14060646
Kaifang Liu, Shubin Liu, Dexiang Feng, Pengwei Xun, Hanjun Jiang, Yanwei Zhang, Gaoliang Yuan, Xusheng Guo
{"title":"Fermentation Products Originated from <i>Bacillus subtilis</i> Promote Hepatic-Intestinal Health in Largemouth Bass, <i>Micropterus salmoides</i>.","authors":"Kaifang Liu, Shubin Liu, Dexiang Feng, Pengwei Xun, Hanjun Jiang, Yanwei Zhang, Gaoliang Yuan, Xusheng Guo","doi":"10.3390/biology14060646","DOIUrl":"10.3390/biology14060646","url":null,"abstract":"<p><p>The fermentation product FP-WeiGuangSu is regarded as a novel, green and efficient antibiotic substitute. Such products constitute one of the principal strategies for addressing bacterial diseases in aquaculture in the future. This study investigates the effects of FPs derived from <i>Bacillus subtilis</i> on the antioxidant capacity and gut microbiota of Largemouth Bass (<i>Micropterus salmoides</i>). Experimental diets containing 0, 1%, 3% and 5% FPs (Control, H1, H2 and H3) were fed to <i>M. salmoides</i>. Although short-term administration of FPs exerted no significant influence on the growth performance of Largemouth Bass, serological findings demonstrated that supplementation with FPs decreased the contents of the liver injury markers ALT, AST and AKP, along with liver MDA content, and enhanced antioxidant capacity (SOD, CAT and GSH-px). Notably, the addition of 1% FPs significantly improved the systemic antioxidant performance (SOD, CAT, GSH-px and T-AOC). Moreover, the FP supplementation increased the expression levels of <i>il-10</i> and <i>IgM</i>, and lipolysis-related genes. The results of gut microbiota analysis revealed that FPs significantly altered the diversity and structure of gut microbiota. The LEfSe results indicated that the microbial marker of the control group was <i>Cetobacterium</i>, those of the H1 group were <i>Bacillus</i> and <i>Mycoplasma</i>, those of the H2 group were <i>Acinetobacter</i>, <i>Paenibacillus</i> and g_unclassified_<i>Rhizobiaceae</i>, and that of the H3 group was <i>Enterococcus</i>. The most significant microbial marker upon the addition of FPs was <i>Paenibacillus</i>, and the pathways for biosynthesis of secondary metabolites, biosynthesis of antibiotics, and biosynthesis of amino acids were significantly activated. The Bugbase analysis results suggested that, compared with the control group, the abundance of anaerobic bacteria in the FP group decreased, while the abundance of microorganisms with mobile-element-containing and oxidative-stress-tolerant phenotypes increased. Hence, this study demonstrated that 1-3% FP dietary supplementation can be used to enhance antioxidant ability, and liver and intestine health of <i>M. salmoides</i> in the aquaculture industry and can be regarded as a promising feed additive in aquaculture.</p>","PeriodicalId":48624,"journal":{"name":"Biology-Basel","volume":"14 6","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12189297/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144498677","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}
引用次数: 0
Neurocognitive Outcomes After Extracranial Surgery and General Anesthesia in Patients with a History of Mild-to-Moderate Traumatic Brain Injury: Systemic Review and Meta-Analysis. 有轻中度创伤性脑损伤病史的患者在颅外手术和全身麻醉后的神经认知结局:系统回顾和荟萃分析。
IF 3.6 3区 生物学
Biology-Basel Pub Date : 2025-05-31 DOI: 10.3390/biology14060640
Zeeshan A Khan, Tahiris A Duran, Dewan Md Sumsuzzman, Ling-Sha Ju, Christoph N Seubert, Anatoly E Martynyuk
{"title":"Neurocognitive Outcomes After Extracranial Surgery and General Anesthesia in Patients with a History of Mild-to-Moderate Traumatic Brain Injury: Systemic Review and Meta-Analysis.","authors":"Zeeshan A Khan, Tahiris A Duran, Dewan Md Sumsuzzman, Ling-Sha Ju, Christoph N Seubert, Anatoly E Martynyuk","doi":"10.3390/biology14060640","DOIUrl":"10.3390/biology14060640","url":null,"abstract":"<p><p>Accelerated neurocognitive decline associated with surgeries under general anesthesia (GA), a phenomenon referred to as postoperative neurocognitive disorder (PND), is a significant public health concern. It not only poses inherent risks but may also contribute to the development of other neurodegenerative disorders. We systematically searched five databases for studies examining cognitive function in patients with mild-to-moderate TBI with (participant) or without (control) subsequent extracranial surgeries/GA. A random effects model was applied to calculate mean differences (MDs) and 95% confidence intervals (CIs). Five outcomes were analyzed post hoc: trail-making tests A and B (TMT-A/B), Glasgow Outcome Scale-Extended (GOSE), and length of stay (LOS) in intensive care units (ICUs) and hospitals. Five studies met the criteria for our meta-analysis. Patients with a history of mild-to-moderate TBI who underwent extracranial surgeries/GA exhibited worse outcomes in TMT-A [MD = 2.04; CI 0.38-3.70; <i>p</i> = 0.016] and TMT-B [MD = 16.59; CI 9.58-23.60; <i>p</i> < 0.001]. Differences in the ICU and hospital LOS and GOSE between the study groups were insignificant. Our results suggest that extracranial surgeries/GA may worsen neurocognitive outcomes without affecting functional recovery in mild-to-moderate TBI patients. Given the limited number of studies identified and the high incidence of TBI, more research on PND in TBI patients is warranted.</p>","PeriodicalId":48624,"journal":{"name":"Biology-Basel","volume":"14 6","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12189922/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144498726","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}
引用次数: 0
Cannabinoid Modulation of Excitability and Short-Term Neuronal Dynamics in the Dorsal and Ventral Hippocampus. 大麻素对海马背侧和腹侧兴奋性和短期神经元动力学的调节。
IF 3.6 3区 生物学
Biology-Basel Pub Date : 2025-05-31 DOI: 10.3390/biology14060642
Giota Tsotsokou, Ioanna-Maria Sotiropoulou, Klearchos Stampolitis, George D Oikonomou, Aikaterini-Paraskevi Avdi, Costas Papatheodoropoulos
{"title":"Cannabinoid Modulation of Excitability and Short-Term Neuronal Dynamics in the Dorsal and Ventral Hippocampus.","authors":"Giota Tsotsokou, Ioanna-Maria Sotiropoulou, Klearchos Stampolitis, George D Oikonomou, Aikaterini-Paraskevi Avdi, Costas Papatheodoropoulos","doi":"10.3390/biology14060642","DOIUrl":"10.3390/biology14060642","url":null,"abstract":"<p><p>Endocannabinoids, acting primarily through CB1 receptors, are critical modulators of neuronal activity, influencing cognitive functions and emotional processing. CB1 receptors are highly expressed in the hippocampus, primarily on GABAergic interneurons, modulating the excitation/inhibition balance. Previous evidence suggests the functional heterogeneity of CB1 receptors along the dorsoventral axis of the hippocampus. However, it is not known whether CB1 receptors differentially modulate basic aspects of the local neuronal network along the hippocampus. This study investigated how CB1 receptor activation modulates excitability, paired-pulse inhibition (PPI), and short-term neuronal dynamics (STND) in the dorsal and ventral CA1 hippocampus under physiologically relevant conditions. Using extracellular recordings from hippocampal slices of male Wistar rats, we compared the effects of two CB1 receptor agonists, ACEA and WIN55,212-2, on network activity in the dorsal and ventral hippocampus. We found that both agonists significantly increased excitability and reduced PPI in the dorsal, but not the ventral, hippocampus. Similarly, CB1 receptor activation modulated STND more prominently in the dorsal hippocampus, reducing facilitation at low frequencies and reversing depression at high frequencies, whereas effects on the ventral region were minimal. These dorsoventral differences in the actions of cannabinoid receptor agonists occurred despite similar CB1 receptor expression levels in both regions, suggesting that functional differences arise from downstream mechanisms rather than receptor density. Pre-application of the GIRK channel blocker Tertiapin-Q occluded the effects of WIN55,212-2 on STND, indicating a significant role of GIRK channel-mediated signaling in CB1 receptor actions. These findings demonstrate that CB1 receptors modulate hippocampal circuitry in a region-specific manner, with the dorsal hippocampus being more sensitive to cannabinoid signaling, likely through differential engagement of intracellular signaling pathways such as GIRK channel activation. These results provide novel insights into how endocannabinoid signaling differentially regulates neuronal dynamics along the dorsoventral axis of the hippocampus. They also have important implications for understanding the role of cannabinoids in hippocampus-dependent behaviors.</p>","PeriodicalId":48624,"journal":{"name":"Biology-Basel","volume":"14 6","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12189292/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144498651","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}
引用次数: 0
Transcriptome and Metabolome Analyses of the Salt Stress Response Mechanism in Lonicera caerulea. 金银花盐胁迫响应机制的转录组和代谢组分析。
IF 3.6 3区 生物学
Biology-Basel Pub Date : 2025-05-31 DOI: 10.3390/biology14060641
Dandan Zang, Yadong Duan, Hengtian Zhao, Ning Wang, Yiming Zhang, Yanmin Wang, Huizi Liu
{"title":"Transcriptome and Metabolome Analyses of the Salt Stress Response Mechanism in <i>Lonicera caerulea</i>.","authors":"Dandan Zang, Yadong Duan, Hengtian Zhao, Ning Wang, Yiming Zhang, Yanmin Wang, Huizi Liu","doi":"10.3390/biology14060641","DOIUrl":"10.3390/biology14060641","url":null,"abstract":"<p><p><i>Lonicera caerulea</i> is a wild fruit species with high edible and medicinal value. However, the molecular regulation and metabolic mechanisms of <i>L. caerulea</i> under salt stress are still unclear. Salt stress causes damage to the cell membrane of <i>L. caerulea</i> and induces changes in malondialdehyde content, relative electrolyte leakage, leaves' stomatal opening, and the water loss rate. It also increases the activity of antioxidant enzymes and the content of soluble sugars. A comprehensive transcriptomic and metabolomic analysis of <i>L. caerulea</i> exposed to salt stress at four different (treatment) time intervals yielded a total of 99,574 unigenes and 1375 metabolites. Among these, 4081, 4042, and 4403 differentially expressed genes (DEGs) were identified in 12 transcriptomes, while 776, 832, and 793 differentially accumulated metabolites (DAMs) were detected in 12 metabolomes. The DEGs play important roles in several signaling pathways, including MAPK signaling, fatty acid metabolism, starch and sucrose metabolism, phenylpropanoid biosynthesis, and plant hormone signal transduction. KEGG pathway enrichment analysis revealed that these DEGs and DAMs are associated with flavonoid and lipid biosynthesis pathways. The combined transcriptomic and metabolomic analyses suggest that flavonoid and fatty acid compounds may be involved in regulating plant responses to salt stress. These findings will lay the foundation for the selection of <i>L. caerulea</i> germplasm resources and the expansion of its cultivation area. These research findings will lay the foundation for the cultivation of salt-tolerant new varieties of <i>L. caerulea</i> and their planting in saline-alkali soils.</p>","PeriodicalId":48624,"journal":{"name":"Biology-Basel","volume":"14 6","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12189683/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144498762","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}
引用次数: 0
Identification of Genomic Variants and Candidate Genes for Reproductive Traits and Growth Traits in Pishan Red Sheep Using Whole-Genome Resequencing. 利用全基因组重测序技术鉴定皮山红羊生殖性状和生长性状的基因组变异和候选基因
IF 3.6 3区 生物学
Biology-Basel Pub Date : 2025-05-30 DOI: 10.3390/biology14060636
Maimaitijiang Muhetapa, Mengting Zhu, Aladaer Qi, Sulaiman Yiming
{"title":"Identification of Genomic Variants and Candidate Genes for Reproductive Traits and Growth Traits in Pishan Red Sheep Using Whole-Genome Resequencing.","authors":"Maimaitijiang Muhetapa, Mengting Zhu, Aladaer Qi, Sulaiman Yiming","doi":"10.3390/biology14060636","DOIUrl":"10.3390/biology14060636","url":null,"abstract":"<p><p>Sheep have evolved remarkable phenotypic diversity through artificial and natural selection, with reproductive traits being pivotal for breeding economics. As a unique genetic resource, Pishan red sheep exhibit exceptional advantages, including perennial estrus, high fecundity, and stable hereditary characteristics, establishing them as an optimal model for investigating reproductive genetics. In this study, we performed whole-genome resequencing of Pishan red sheep, generating 9084.81 Gb of raw data and identifying 53,968,686 high-quality single-nucleotide polymorphisms (SNPs). Through selective sweep analysis, 92 genomic regions under selection were detected, containing 90 positional candidate genes significantly associated with growth, reproduction, and immune functions. Notably, we revealed BMPRIB, UNC5C, PDLIM5, GRID2, and HPGDS as core positional candidate genes influencing litter size, operating through the TGF-beta and Thyroid hormone signaling pathways. A genome-wide association study (GWAS) further identified 59 trait-related SNPs, including 39 loci linked to growth traits (affecting positional candidate genes such as PROM1, TAPT1, LDB2, and KIF16B) and 20 loci of positional candidate genes associated with reproductive traits (involving ASPA, RAP1GAP2, PHIP, and WDR82).These findings not only elucidate the molecular basis of superior reproductive performance in Pishan red sheep, but also provide functional markers for precision breeding.</p>","PeriodicalId":48624,"journal":{"name":"Biology-Basel","volume":"14 6","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12189700/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144498693","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}
引用次数: 0
Recent Advances in the Therapeutic Effects and Molecular Mechanisms of Baicalin. 黄芩苷的治疗作用及分子机制研究进展。
IF 3.6 3区 生物学
Biology-Basel Pub Date : 2025-05-30 DOI: 10.3390/biology14060637
Xiaoyuan Qiu, Renyin Huang, Junke Xie, Shanshan Luo, Xiang Cheng, Jing Cui, Desheng Hu
{"title":"Recent Advances in the Therapeutic Effects and Molecular Mechanisms of Baicalin.","authors":"Xiaoyuan Qiu, Renyin Huang, Junke Xie, Shanshan Luo, Xiang Cheng, Jing Cui, Desheng Hu","doi":"10.3390/biology14060637","DOIUrl":"10.3390/biology14060637","url":null,"abstract":"<p><p>Baicalin, a kind of polyphenolic flavonoid, is a major bioactive flavone derived from the root of <i>Scutellaria baicalensis</i>, which has been widely utilized in clinical practice in China for thousands of years. In recent years, it has attracted increasing attention due to its potential therapeutic properties observed in preclinical studies involving various disease models. However, the precise mechanisms underlying its biological activities have not been fully elucidated. This review summarizes recent research progress on the molecular mechanisms through which baicalin exerts its effects, particularly in tumor suppression, cardiovascular protection, neuronal preservation, and glucose and lipid metabolism regulation in murine models. Additionally, we discuss the delivery methods of baicalin and its transformation by intestinal microbiota.</p>","PeriodicalId":48624,"journal":{"name":"Biology-Basel","volume":"14 6","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12190052/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144498750","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}
引用次数: 0
Overcoming Clusterin-Induced Chemoresistance in Cancer: A Computational Study Using a Fragment-Based Drug Discovery Approach. 克服簇蛋白诱导的癌症化疗耐药:使用基于片段的药物发现方法的计算研究。
IF 3.6 3区 生物学
Biology-Basel Pub Date : 2025-05-30 DOI: 10.3390/biology14060639
Engelo John Gabriel V Caro, Marineil C Gomez, Po-Wei Tsai, Lemmuel L Tayo
{"title":"Overcoming Clusterin-Induced Chemoresistance in Cancer: A Computational Study Using a Fragment-Based Drug Discovery Approach.","authors":"Engelo John Gabriel V Caro, Marineil C Gomez, Po-Wei Tsai, Lemmuel L Tayo","doi":"10.3390/biology14060639","DOIUrl":"10.3390/biology14060639","url":null,"abstract":"<p><p>Clusterin is one of the many known proteins implicated in cancer chemoresistance, which hinders the effectiveness of chemotherapy. This study aimed to design novel inhibitors targeting clusterin using fragment-based drug discovery (FBDD). This approach aims to develop new medicines by identifying small, simple molecules known as \"fragments\" that can bind to a specific target, such as a disease-causing protein. In this study, a primary ligand-binding site and an allosteric site on the clusterin molecule were identified through hotspot analysis. We screened commercially available fragment libraries for anti-cancer activity and applied the \"rule of three\" to ensure drug-like properties. The highest-affinity fragment underwent \"fragment-growing\" to develop potential drug candidates. After docking and toxicity screening, 194 candidate drugs were identified. Quantitative structure-activity relationship (QSAR) analysis revealed that the chemical size and complexity of the fragments significantly contributed to their binding affinity. Pharmacokinetic analyses of candidate drugs from FBDD followed by molecular dynamics simulation of the top 1 final candidate drug precursor demonstrated comparatively better affinity (average = -34.01 kcal/mol) than the reference compound (average = -6.15 kcal/mol) and significant ligand flexibility. This study offers a potential strategy to identify fragments or molecules that may serve as drugs against clusterin-related chemoresistance.</p>","PeriodicalId":48624,"journal":{"name":"Biology-Basel","volume":"14 6","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12189888/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144498730","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}
引用次数: 0
DoDELLA-GAI2 Integrates Gibberellin and Ethylene Signaling to Regulate Chinese Yam (Dioscorea opposita) Tuber Development. 整合赤霉素和乙烯信号的DoDELLA-GAI2调控山药块茎发育
IF 3.6 3区 生物学
Biology-Basel Pub Date : 2025-05-30 DOI: 10.3390/biology14060635
Mingran Ge, Yanfang Zhang, Yanping Xing, Linan Xing, Huiqin Miao, Xiuwen Huo
{"title":"DoDELLA-GAI2 Integrates Gibberellin and Ethylene Signaling to Regulate Chinese Yam (<i>Dioscorea opposita</i>) Tuber Development.","authors":"Mingran Ge, Yanfang Zhang, Yanping Xing, Linan Xing, Huiqin Miao, Xiuwen Huo","doi":"10.3390/biology14060635","DOIUrl":"10.3390/biology14060635","url":null,"abstract":"<p><p>Yam (<i>Dioscorea opposita</i>) tuber development is a complex process regulated by various phytohormones, with gibberellin (GA) playing a crucial role. However, the underlying mechanisms and interaction of GA with other phytohormone pathways on yam tuber development remain incompletely understood. This study investigated the regulatory role of GA and its crosstalk with other phytohormones during yam tuber growth through phenotypic, cytological, physiological, and transcriptomic as well as targeted phytohormone metabolomics analyses. The results reveal that exogenous GA promoted tuber enlargement increases vascular bundle and the number and diameter of sieve tubes, and alters the expression of GA anabolism genes and GA signal transduction pathways. Integrated transcriptome and targeted metabolomics analyses revealed coordinated changes in GA and ethylene (ETH) biosynthesis and signaling pathways during tuber development, particularly <i>DELLA-GAI2</i> acting as a negative regulator of GA signaling. Overexpression of <i>DoDELLA-GAI2</i> in transgenic tobacco significantly reduced GA level, starch, cytokinin (CTK), and ETH content, as well as aerenchyma tissue growth and parenchyma cell size. Exogenous GA and ethephon treatments increased GA, starch, CTK, and ETH content, and downregulated <i>DoDELLA-GAI2</i> gene expression. The yeast two-hybrid and bimolecular fluorescence complementation (BiFC) assays confirmed a direct interaction between <i>DoDELLA-GAI2</i> and <i>DoMTCPB</i>, an upstream gene-encoding key enzyme in ETH biosynthesis. <i>DoDELLA-GAI2</i> acts as a negative regulator of ETH synthesis by interacting with <i>DoMTCPB</i>. GA-induced degradation of <i>DoDELLA</i>-<i>GAI2</i> relieves this inhibition, promoting ETH production and contributing to tuber growth. Taken together, our findings reveal a novel mechanism based on <i>DoDELLA-GAI2</i> integrating the GA and ETH signaling processes to regulate tuber development in <i>D. opposita</i>, offering a potential target for improving yam crop productivity.</p>","PeriodicalId":48624,"journal":{"name":"Biology-Basel","volume":"14 6","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12189092/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144498657","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}
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