Biomolecules最新文献

{"title":"<i>Astragalus membranaceus</i>: A Traditional Chinese Medicine with Multifaceted Impacts on Breast Cancer Treatment.","authors":"Zhong Tang, Xuefei Tian","doi":"10.3390/biom14101339","DOIUrl":"https://doi.org/10.3390/biom14101339","url":null,"abstract":"<p><p>Breast cancer, the most prevalent malignant tumor among women globally, remains a critical area of focus for researchers striving to refine therapeutic approaches. As an important component of traditional Chinese medicine, <i>Astragalus membranaceus</i> (AM) has demonstrated potential for multifaceted impacts on breast cancer treatment through various mechanisms. To guide clinical practice and further explore the under-researched field of AM in breast cancer treatment, this paper mainly reviews the regulatory roles of AM-derived compounds and extracts on breast cancer cell proliferation, migration, invasion, and chemoresistance. Furthermore, this study delves into the synergistic effects observed when AM is co-administered with chemotherapeutic agents, including the enhancement of chemosensitivity, mitigation of toxic side effects, and reversal of drug resistance. This review indicates that AM holds promise not only as a therapy in breast cancer treatment but also paves the way for innovative integrated treatment approaches that combine the benefits of traditional medicine with modern pharmaceuticals. Nevertheless, future research endeavors are also urged to elucidate the in vivo pharmacological effects and underlying mechanisms of AM to inform more effective clinical treatment strategies.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11506204/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142494413","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}

{"title":"Correction: Choi et al. β-Ionone Attenuates Dexamethasone-Induced Suppression of Collagen and Hyaluronic Acid Synthesis in Human Dermal Fibroblasts. <i>Biomolecules</i> 2021, <i>11</i>, 619.","authors":"Dabin Choi, Wesuk Kang, Soyoon Park, Bomin Son, Taesun Park","doi":"10.3390/biom14101337","DOIUrl":"https://doi.org/10.3390/biom14101337","url":null,"abstract":"<p><p>The authors would like to modify the Conflicts of Interest section of the published paper [...].</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11506704/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142494461","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}

{"title":"Cooperative Substructure and Energetics of Allosteric Regulation of the Catalytic Core of the E3 Ubiquitin Ligase Parkin by Phosphorylated Ubiquitin.","authors":"Xiang Ye, Sravya Kotaru, Rosana Lopes, Shannen Cravens, Mauricio Lasagna, A Joshua Wand","doi":"10.3390/biom14101338","DOIUrl":"https://doi.org/10.3390/biom14101338","url":null,"abstract":"<p><p>Mutations in the parkin gene product Parkin give rise to autosomal recessive juvenile parkinsonism. Parkin is an E3 ubiquitin ligase that is a critical participant in the process of mitophagy. Parkin has a complex structure that integrates several allosteric signals to maintain precise control of its catalytic activity. Though its allosterically controlled structural reorganization has been extensively characterized by crystallography, the energetics and mechanisms of allosteric regulation of Parkin are much less well understood. Allostery is fundamentally linked to the energetics of the cooperative (sub)structure of the protein. Herein, we examine the mechanism of allosteric activation by phosphorylated ubiquitin binding to the enzymatic core of Parkin, which lacks the antagonistic Ubl domain. In this way, the allosteric effects of the agonist phosphorylated ubiquitin can be isolated. Using native-state hydrogen exchange monitored by mass spectrometry, we find that the five structural domains of the core of Parkin are energetically distinct. Nevertheless, association of phosphorylated ubiquitin destabilizes structural elements that bind the ubiquitin-like domain antagonist while promoting the dissociation of the catalytic domain and energetically poises the protein for transition to the fully activated structure.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11506642/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142516279","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}

{"title":"tRNA and tsRNA: From Heterogeneity to Multifaceted Regulators.","authors":"Yun Li, Zongyu Yu, Wenlin Jiang, Xinyi Lyu, Ailian Guo, Xiaorui Sun, Yiting Yang, Yunfang Zhang","doi":"10.3390/biom14101340","DOIUrl":"https://doi.org/10.3390/biom14101340","url":null,"abstract":"<p><p>As the most ancient RNA, transfer RNAs (tRNAs) play a more complex role than their constitutive function as amino acid transporters in the protein synthesis process. The transcription and maturation of tRNA in cells are subject to stringent regulation, resulting in the formation of tissue- and cell-specific tRNA pools with variations in tRNA overall abundance, composition, modification, and charging levels. The heterogeneity of tRNA pools contributes to facilitating the formation of histocyte-specific protein expression patterns and is involved in diverse biological processes. Moreover, tRNAs can be recognized by various RNase under physiological and pathological conditions to generate tRNA-derived small RNAs (tsRNAs) and serve as small regulatory RNAs in various biological processes. Here, we summarize these recent insights into the heterogeneity of tRNA and highlight the advances in the regulation of tRNA function and tsRNA biogenesis by tRNA modifications. We synthesize diverse mechanisms of tRNA and tsRNA in embryonic development, cell fate determination, and epigenetic inheritance regulation. We also discuss the potential clinical applications based on the new knowledge of tRNA and tsRNA as diagnostic and prognostic biomarkers and new therapeutic strategies for multiple diseases.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11506809/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142494471","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}

{"title":"Chemical Profiling of Polar Lipids and the Polyphenolic Fraction of Commercial Italian <i>Phaseolus</i> Seeds by UHPLC-HRMS and Biological Evaluation.","authors":"Vadym Samukha, Francesca Fantasma, Gilda D'Urso, Ester Colarusso, Anna Schettino, Noemi Marigliano, Maria Giovanna Chini, Gabriella Saviano, Vincenzo De Felice, Gianluigi Lauro, Francesco Maione, Giuseppe Bifulco, Agostino Casapullo, Maria Iorizzi","doi":"10.3390/biom14101336","DOIUrl":"https://doi.org/10.3390/biom14101336","url":null,"abstract":"<p><p>The common bean (<i>Phaseolus vulgaris</i> L.) is one of the oldest food crops in the world. In this study, the ultra-high-performance liquid chromatography high-resolution mass spectrometry (UHPLC-MS/MS) technique was used to characterize the polar lipid composition and polyphenolic fraction of five bean varieties commonly consumed in Italy: Cannellino (PVCA), Controne (PVCO), Borlotti (PVBO), Stregoni (PVST), and Vellutina (PVVE). Lipid content represents a minor fraction of the whole metabolome in dry beans, and little is known about their polar lipids, which could be potentially bioactive components. Thirty-three compounds were detected through UHPLC-MS/MS, including oxylipins, phospholipids, N-acyl glycerolipids, and several fatty acids. The dichloromethane extracts were subjected to principal component analysis (PCA), with the results showing greater differentiation for the Borlotti variety. Moreover, 27 components belonging to different polyphenol classes, such as phenolic acids, flavonoids, catechins, anthocyanins and their glycosides, and some saponins, were identified in the hydroalcoholic seed extracts. In addition, the mineral content of the beans was determined. Considering the high number of compounds in the five apolar seed extracts, all samples were examined to determine their in vitro inhibitory activity against the enzyme cyclooxygenase-2 (COX-2), which is inducible in inflammatory cells and mediates inflammatory responses. Only PVCO showed the best inhibition of the COX-2 enzyme with an IC₅₀ = 31.15 ± 2.16 µg/mL. In light of these results, the potential anti-inflammatory properties of PVCO were evaluated in the LPS-stimulated murine macrophage cell line J774A.1. Herein, we demonstrate, for the first time, that PVCO at 30 µg/mL can significantly reduce the release of TNF-α, with a less significant anti-inflammatory effect being observed in terms of IL-6 release.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11505683/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142494456","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}

{"title":"Potential Roles of IP₃ Receptors and Calcium in Programmed Cell Death and Implications in Cardiovascular Diseases.","authors":"Chanon Piamsiri, Nadezhda Fefelova, Sri Harika Pamarthi, Judith K Gwathmey, Siriporn C Chattipakorn, Nipon Chattipakorn, Lai-Hua Xie","doi":"10.3390/biom14101334","DOIUrl":"https://doi.org/10.3390/biom14101334","url":null,"abstract":"<p><p>Inositol 1,4,5-trisphosphate receptors (IP₃Rs) play a crucial role in maintaining intracellular/cytosolic calcium ion (Ca²⁺_i) homeostasis. The release of Ca²⁺ from IP₃Rs serves as a second messenger and a modulatory factor influencing various intracellular and interorganelle communications during both physiological and pathological processes. Accumulating evidence from in vitro, in vivo, and clinical studies supports the notion that the overactivation of IP₃Rs is linked to the pathogenesis of various cardiac conditions. The overactivation of IP₃Rs results in the dysregulation of Ca²⁺ concentration ([Ca²⁺]) within cytosolic, mitochondrial, and nucleoplasmic cellular compartments. In cardiovascular pathologies, two isoforms of IP₃Rs, i.e., IP₃R1 and IP₃R2, have been identified. Notably, IP₃R1 plays a pivotal role in cardiac ischemia and diabetes-induced arrhythmias, while IP₃R2 is implicated in sepsis-induced cardiomyopathy and cardiac hypertrophy. Furthermore, IP₃Rs have been reported to be involved in various programmed cell death (PCD) pathways, such as apoptosis, pyroptosis, and ferroptosis underscoring their multifaceted roles in cardiac pathophysiology. Based on these findings, it is evident that exploring potential therapeutic avenues becomes crucial. Both genetic ablation and pharmacological intervention using IP₃R antagonists have emerged as promising strategies against IP₃R-related pathologies suggesting their potential therapeutic potency. This review summarizes the roles of IP₃Rs in cardiac physiology and pathology and establishes a foundational understanding with a particular focus on their involvement in the various PCD pathways within the context of cardiovascular diseases.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11506173/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142494547","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}

{"title":"Stress-Induced Evolution of the Nucleolus: The Role of Ribosomal Intergenic Spacer (rIGS) Transcripts.","authors":"Anastasia A Gavrilova, Margarita V Neklesova, Yuliya A Zagryadskaya, Irina M Kuznetsova, Konstantin K Turoverov, Alexander V Fonin","doi":"10.3390/biom14101333","DOIUrl":"https://doi.org/10.3390/biom14101333","url":null,"abstract":"<p><p>It became clear more than 20 years ago that the nucleolus not only performs the most important biological function of assembling ribonucleic particles but is also a key controller of many cellular processes, participating in cellular adaptation to stress. The nucleolus's multifunctionality is due to the peculiarities of its biogenesis. The nucleolus is a multilayered biomolecular condensate formed by liquid-liquid phase separation (LLPS). In this review, we focus on changes occurring in the nucleolus during cellular stress, molecular features of the nucleolar response to abnormal and stressful conditions, and the role of long non-coding RNAs transcribed from the intergenic spacer region of ribosomal DNA (IGS rDNA).</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11505599/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142494555","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}

{"title":"Increased Cardiometabolic Risk in Men with Hypoprolactinemia: A Pilot Study.","authors":"Robert Krysiak, Karolina Kowalcze, Witold Szkróbka, Bogusław Okopień","doi":"10.3390/biom14101335","DOIUrl":"https://doi.org/10.3390/biom14101335","url":null,"abstract":"<p><p>Low prolactin levels in men predispose them to mood disturbances, sexual dysfunction, and diabetes. The purpose of the current study was to assess cardiometabolic risk in males with hypoprolactinemia. This prospective study included three age-matched groups of young and middle-aged men: individuals with cabergoline-induced hypoprolactinemia (<i>n</i> = 15), cabergoline-treated subjects with prolactin levels within the reference range (<i>n</i> = 20), and untreated men with normal prolactin levels (<i>n</i> = 31). In men with hypoprolactinemia, the cabergoline dose was reduced in order to normalize prolactin concentration. Anthropometric parameters, blood pressure, QRISK3 score; plasma concentrations of prolactin, glucose, insulin, lipids, uric acid, high-sensitivity C-reactive protein (hsCRP), fibrinogen, homocysteine, and testosterone; whole-blood levels of glycated hemoglobin (HbA_1C); urinary albumin-to-creatinine ratio (UACR); and carotid intima-media thickness were assessed at baseline and six months later. Men with hypoprolactinemia were characterized by higher body mass index, fat content, waist circumference, systolic blood pressure, fasting and 2 h post-load glucose, HbA_1C, HOMA1-IR, uric acid, hsCRP, fibrinogen, homocysteine, and UACR; by lower HDL cholesterol and testosterone; by greater intima-media thickness; and by a higher QRISK3 score than their peers with normal prolactin levels. There were no statistically significant differences in the measured parameters between both groups of men with normal prolactin levels. Normalization of prolactin concentration was accompanied by normalization of biochemical variables, systolic blood pressure, and QRISK3 score. Although cabergoline dose reduction did not cause statistically significant changes in the remaining anthropometric parameters and intima-media thickness, six months later, they did not differ from those observed in the remaining study groups. Our findings suggest that iatrogenic hypoprolactinemia is associated with increased cardiometabolic risk, which is reversible and resolves after the normalization of prolactin levels.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11506548/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142494516","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}

{"title":"Identification of Multifunctional Putative Bioactive Peptides in the Insect Model Red Palm Weevil (<i>Rhynchophorus ferrugineus</i>).","authors":"Carmen Scieuzo, Roberta Rinaldi, Fabiana Giglio, Rosanna Salvia, Mohammed Ali AlSaleh, Jernej Jakše, Arnab Pain, Binu Antony, Patrizia Falabella","doi":"10.3390/biom14101332","DOIUrl":"https://doi.org/10.3390/biom14101332","url":null,"abstract":"<p><p>Innate immunity, the body's initial defense against bacteria, fungi, and viruses, heavily depends on antimicrobial peptides (AMPs), which are small molecules produced by all living organisms. Insects, with their vast biodiversity, are one of the most abundant and innovative sources of AMPs. In this study, AMPs from the red palm weevil (RPW) <i>Rhynchophorus ferrugineus</i> (Coleoptera: Curculionidae), a known invasive pest of palm species, were examined. The AMPs were identified in the transcriptomes from different body parts of male and female adults, under different experimental conditions, including specimens collected from the field and those reared in the laboratory. The RPW transcriptomes were examined to predict antimicrobial activity, and all sequences putatively encoding AMPs were analyzed using several machine learning algorithms available in the CAMP_R3 database. Additionally, anticancer, antiviral, and antifungal activity of the peptides were predicted using iACP, AVPpred, and Antifp server tools, respectively. Physicochemical parameters were assessed using the Antimicrobial Peptide Database Calculator and Predictor. From these analyses, 198 putatively active peptides were identified, which can be tested in future studies to validate the <i>in silico</i> predictions. Genome-wide analysis revealed that several AMPs have predominantly emerged through gene duplication. Noticeably, we detect a newly originated defensin allele from an ancestral defensin via the deletion of two amino acids following gene duplication in RPW, which may confer an enhanced resilience to microbial infection. Our study shed light on AMP gene families and shows that high duplication and deletion rates are essential to achieve a diversity of antimicrobial mechanisms; hence, we propose the RPW AMPs as a model for exploring gene duplication and functional variations against microbial infection.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11506011/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142494512","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}

{"title":"A Survey on Computational Methods in Drug Discovery for Neurodegenerative Diseases.","authors":"Caterina Vicidomini, Francesco Fontanella, Tiziana D'Alessandro, Giovanni N Roviello","doi":"10.3390/biom14101330","DOIUrl":"https://doi.org/10.3390/biom14101330","url":null,"abstract":"<p><p>Currently, the age structure of the world population is changing due to declining birth rates and increasing life expectancy. As a result, physicians worldwide have to treat an increasing number of age-related diseases, of which neurological disorders represent a significant part. In this context, there is an urgent need to discover new therapeutic approaches to counteract the effects of neurodegeneration on human health, and computational science can be of pivotal importance for more effective neurodrug discovery. The knowledge of the molecular structure of the receptors and other biomolecules involved in neurological pathogenesis facilitates the design of new molecules as potential drugs to be used in the fight against diseases of high social relevance such as dementia, Alzheimer's disease (AD) and Parkinson's disease (PD), to cite only a few. However, the absence of comprehensive guidelines regarding the strengths and weaknesses of alternative approaches creates a fragmented and disconnected field, resulting in missed opportunities to enhance performance and achieve successful applications. This review aims to summarize some of the most innovative strategies based on computational methods used for neurodrug development. In particular, recent applications and the state-of-the-art of molecular docking and artificial intelligence for ligand- and target-based approaches in novel drug design were reviewed, highlighting the crucial role of in silico methods in the context of neurodrug discovery for neurodegenerative diseases.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11506269/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142494430","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}