Biomolecules最新文献

{"title":"Voltage-Dependent Anion Channels in Male Reproductive Cells: Players in Healthy Fertility?","authors":"Stefano Conti Nibali, Giuseppe Battiato, Xena Giada Pappalardo, Vito De Pinto","doi":"10.3390/biom14101290","DOIUrl":"https://doi.org/10.3390/biom14101290","url":null,"abstract":"<p><p>Male infertility affects nearly 50% of infertile couples, with various underlying causes, including endocrine disorders, testicular defects, and environmental factors. Spermatozoa rely on mitochondrial oxidative metabolism for motility and fertilization, with mitochondria playing a crucial role in sperm energy production, calcium regulation, and redox balance. Voltage-dependent anion channels (VDACs), located on the outer mitochondrial membrane, regulate energy and metabolite exchange, which are essential for sperm function. This review offers an updated analysis of VDACs in the male reproductive system, summarizing recent advances in understanding their expression patterns, molecular functions, and regulatory mechanisms. Although VDACs have been widely studied in other tissues, their specific roles in male reproductive physiology still remain underexplored. Special attention is given to the involvement of VDAC2/3 isoforms, which may influence mitochondrial function in sperm cells and could be implicated in male fertility disorders. This update provides a comprehensive framework for future research in reproductive biology, underscoring the significance of VDACs as a molecular link between mitochondrial function and male fertility.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11506323/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142494477","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":"Phosphatidylserine: A Novel Target for Ischemic Stroke Treatment.","authors":"Jiaqi Guo, Jiachen He, Shuaili Xu, Xi Chen, Zhanwei Zhu, Xunming Ji, Di Wu","doi":"10.3390/biom14101293","DOIUrl":"https://doi.org/10.3390/biom14101293","url":null,"abstract":"<p><p>Over the past 40 years, research has heavily emphasized stroke treatments that directly target ischemic cascades after stroke onset. Much attention has focused on studying neuroprotective drugs targeting one aspect of the ischemic cascade. However, the single-target therapeutic approach resulted in minimal clinical benefit and poor outcomes in patients. Considering the ischemic cascade is a multifaceted and complex pathophysiological process with many interrelated pathways, the spotlight is now shifting towards the development of neuroprotective drugs that affect multiple aspects of the ischemic cascade. Phosphatidylserine (PS), known as the \"eat-me\" signal, is a promising candidate. PS is involved in many pathophysiological changes in the central nervous system after stroke onset, including apoptosis, inflammation, coagulation, and neuronal regeneration. Moreover, PS might also exert various roles in different phases after stroke onset. In this review, we describe the synthesis, regulation, and function of PS under physiological conditions. Furthermore, we also summarize the different roles of PS after stroke onset. More importantly, we also discuss several treatment strategies that target PS. We aim to advocate a novel stroke care strategy by targeting PS through a translational perspective.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11506168/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142494540","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":"Modulation of Carnitine Palmitoyl Transferase 1b Expression and Activity in Muscle Pathophysiology in Osteoarthritis and Osteoporosis.","authors":"Chiara Greggi, Manuela Montanaro, Maria Giovanna Scioli, Martina Puzzuoli, Sonia Gino Grillo, Manuel Scimeca, Alessandro Mauriello, Augusto Orlandi, Elena Gasbarra, Riccardo Iundusi, Sabina Pucci, Umberto Tarantino","doi":"10.3390/biom14101289","DOIUrl":"https://doi.org/10.3390/biom14101289","url":null,"abstract":"<p><p>In the pathophysiology of osteoarthritis and osteoporosis, articular cartilage and bone represent the target tissues, respectively, but muscle is also involved. Since many changes in energy metabolism occur in muscle with aging, the aim of the present work was to investigate the involvement of carnitine palmitoyl transferase 1b (Cpt1b) in the muscle pathophysiology of the two diseases. Healthy subjects (CTR, <i>n</i> = 5), osteoarthritic (OA, <i>n</i> = 10), and osteoporotic (OP, <i>n</i> = 10) patients were enrolled. Gene expression analysis conducted on muscle and myoblasts showed up-regulation of <i>CPT1B</i> in OA patients; this result was confirmed by immunohistochemical and immunofluorescence analyses and enzyme activity assay, which showed increased Cpt1b activity in OA muscle. In addition, CPT1B expression resulted down-regulated in cultured OP myoblasts. Given the potential involvement of Cpt1b in the modulation of oxidative stress, we investigated ROS levels, which were found to be lower in OA myoblasts, and gene expression of nicotinamide adenine dinucleotide phosphate hydrogen oxidase 4 (Nox4), which resulted up-regulated in OA cells. Finally, the immunofluorescence of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (Bnip3) showed a decreased expression in OP myoblasts, with respect to CTR and OA. Contextually, through an ultrastructural analysis conducted by Transmission Electron Microscopy (TEM), the presence of aberrant mitochondria was observed in OP muscle. This study highlights the potential role of Cpt1b in the regulation of muscle homeostasis in both osteoarthritis and osteoporosis, allowing for the expansion of the current knowledge of what are the molecular biological pathways involved in the regulation of muscle physiology in both diseases.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11505991/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142494531","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":"Alternative Splicing of the Last <i>TKFC</i> Intron Yields Transcripts Differentially Expressed in Human Tissues That Code In Vitro for a Protein Devoid of Triokinase and FMN Cyclase Activity.","authors":"María Jesús Costas, Ana Couto, Alicia Cabezas, Rosa María Pinto, João Meireles Ribeiro, José Carlos Cameselle","doi":"10.3390/biom14101288","DOIUrl":"10.3390/biom14101288","url":null,"abstract":"<p><p>The 18-exon human <i>TKFC</i> gene codes for dual-activity triokinase and FMN cyclase (TKFC) in an ORF, spanning from exon 2 to exon 18. In addition to TKFC-coding transcripts (classified as <i>tkfc</i> type by their intron-17 splice), databases contain evidence for alternative <i>TKFC</i> transcripts, but none of them has been expressed, studied, and reported in the literature. A novel full-ORF transcript was cloned from brain cDNA and sequenced (accession no. DQ344550). It results from an alternative 3' splice-site in intron 17. The cloned cDNA contains an ORF also spanning from exon 2 to exon 18 of the <i>TKFC</i> gene but with a 56-nt insertion between exons 17 and 18 (classified as <i>tkfc_ins56</i> type). This insertion introduces an in-frame stop, and the resulting ORF codes for a shorter TKFC variant, which, after expression, is enzymatically inactive. <i>TKFC</i> intron-17 splicing was found to be differentially expressed in human tissues. In a multiple-tissue northern blot using oligonucleotide probes, the liver showed a strong expression of the <i>tkfc</i>-like splice of intron 17, and the heart preferentially expressed the <i>tkfc_ins56</i>-like splice. Through a comparison to global expression data from massive-expression studies of human tissues, it was inferred that the intestine preferentially expresses <i>TKFC</i> transcripts that contain neither of those splices. An analysis of transcript levels quantified by RNA-Seq in the GTEX database revealed an exception to this picture due to the occurrence of a non-coding short transcript with a <i>tkfc</i>-like splice. Altogether, the results support the occurrence of potentially relevant transcript variants of the <i>TKFC</i> gene, differentially expressed in human tissues. (This work is dedicated in memoriam to Professor Antonio Sillero, 1938-2024, for his lifelong mentoring and his pioneering work on triokinase).</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11506722/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142494435","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":"Modulating <i>OCA2</i> Expression as a Promising Approach to Enhance Skin Brightness and Reduce Dark Spots.","authors":"Eunbyul Cho, Kyong Eun Hyung, Yun-Ho Choi, Hyeyeon Chun, Daehyun Kim, Seung-Hyun Jun, Nae-Gyu Kang","doi":"10.3390/biom14101284","DOIUrl":"10.3390/biom14101284","url":null,"abstract":"<p><p>The oculocutaneous albinism II (<i>OCA2</i>) gene encodes a melanosomal transmembrane protein involved in melanogenesis. Recent genome-wide association studies have identified several single nucleotide polymorphisms within <i>OCA2</i> genes that are involved in skin pigmentation. Nevertheless, there have been no attempts to modulate this gene to improve skin discoloration. Accordingly, our aim was to identify compounds that can reduce <i>OCA2</i> expression and to develop a formula that can improve skin brightness and reduce hyperpigmented spots. In this study, we investigated the effects of <i>OCA2</i> expression reduction on melanin levels, melanosome pH, and autophagy induction through siRNA knockdown. Additionally, we identified several bioactives that effectively reduce <i>OCA2</i> expression. Ultimately, in a clinical trial, we demonstrated that topical application of those compounds significantly improved skin tone and dark spots compared to vitamin C, a typical brightening agent. These findings demonstrate that <i>OCA2</i> is a promising target for the development of efficacious cosmetics and therapeutics designed to treat hyperpigmentation.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11506640/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142494530","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":"Candidate Molecular Biomarkers of Traumatic Brain Injury: A Systematic Review.","authors":"Tatiana V Butkova, Kristina A Malsagova, Valeriya I Nakhod, Denis V Petrovskiy, Alexander A Izotov, Evgenii I Balakin, Ksenia A Yurku, Alexey S Umnikov, Vasiliy I Pustovoyt, Anna L Kaysheva","doi":"10.3390/biom14101283","DOIUrl":"https://doi.org/10.3390/biom14101283","url":null,"abstract":"<p><p>Traumatic brain injury (TBI) is one of the leading causes of mortality and disability among young and middle-aged individuals. Adequate and timely diagnosis of primary brain injuries, as well as the prompt prevention and treatment of secondary injury mechanisms, significantly determine the potential for reducing mortality and severe disabling consequences. Therefore, it is crucial to have objective markers that indicate the severity of the injury. A number of molecular factors-proteins and metabolites-detected in the blood immediately after trauma and associated with the development and severity of TBI can serve in this role. TBI is a heterogeneous condition with respect to its etiology, clinical form, and genesis, being accompanied by brain cell damage and disruption of blood-brain barrier permeability. Two oppositely directed flows of substances and signals are observed: one is the flow of metabolites, proteins, and nucleic acids from damaged brain cells into the bloodstream through the damaged blood-brain barrier; the other is the infiltration of immune cells (neutrophils and macrophages) and serological proteins. Both flows aggravate brain tissue damage after TBI. Therefore, it is extremely important to study the key signaling events that regulate these flows and repair the damaged tissues, as well as to enhance the effectiveness of treatments for patients after TBI.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11506336/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142494450","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":"Understanding the Key Determinants of Cardiovascular and Metabolic Disease Progression to Develop Effective Therapeutic Strategies.","authors":"Adriana Georgescu","doi":"10.3390/biom14101281","DOIUrl":"https://doi.org/10.3390/biom14101281","url":null,"abstract":"<p><p>Cardiovascular disease (CVD) is a general term that is used to describe a range of conditions affecting the cardiovascular system [...].</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11505940/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142494473","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":"New Insights into Health Conditions Related to Malfunctions in Clock Genes.","authors":"Kaja Majewska, Mikołaj Seremak, Katarzyna Podhorodecka, Maria Derkaczew, Bartosz Kędziora, Paulina Boniecka, Kamila Zglejc-Waszak, Agnieszka Korytko, Małgorzata Pawłowicz, Joanna Wojtkiewicz","doi":"10.3390/biom14101282","DOIUrl":"https://doi.org/10.3390/biom14101282","url":null,"abstract":"<p><p>Chronotypes play a crucial role in regulating sleep-wake cycles and overall health. The aim of this study was to investigate chronotype, sleep quality, polymorphisms of clock genes and the level of leptin in serum. We used standardized questionnaires to assess chronotype and sleep quality. Genetic analysis was performed to determine the selected clock gene polymorphism. Serum leptin level was measured by the Elisa method. The results showed that serum leptin concentration was elevated in women, as well as in men who had a high waist-to-hip ratio (WHR) and body mass index (BMI). The evidence indicated that younger students (<22 years old) were most likely to experience poor sleep quality. Nevertheless, our multivariate analysis revealed that young age and a morning-oriented chronotype were associated with better sleep quality. We noted that clock gene polymorphisms were present in 28.6% of the participants. Moreover, polymorphisms of PER1 c.2247C>T (rs2735611) and PER2 c.-12C>G (rs2304672) genes were associated with serum leptin level and chronotype, respectively. These findings provide insights into the relationships between chronotype, sleep quality, clock gene polymorphisms and obesity risk in biomedical students. Understanding these factors can contribute to better sleep management and potential interventions to improve health outcomes in humans.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11505610/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142494539","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 and Biological Characterization of Metabolites from <i>Silene viridiflora</i> Using Mass Spectrometric and Cell-Based Assays.","authors":"Nilufar Z Mamadalieva, Alexey Koval, Maksud M Dusmuratov, Hidayat Hussain, Vladimir L Katanaev","doi":"10.3390/biom14101285","DOIUrl":"https://doi.org/10.3390/biom14101285","url":null,"abstract":"<p><p>A comprehensive metabolite profiling of the medicinal plant <i>Silene viridiflora</i> using an UHPLC-ESI-MS/MS method is described for the first time. A total of 71 compounds were identified and annotated, the most common of which were flavonoids, triterpene glycosides, and ecdysteroids. The three major compounds schaftoside, 26-hydroxyecdysone, and silviridoside can be chosen as the markers for the assessment of the quality of <i>S. viridiflora</i> preparations. The methanol extract and a variety of metabolites identified in <i>S. viridiflora</i> were screened for their cytotoxic and Wnt pathway-inhibiting activities against triple-negative breast cancer (TNBC), the deadliest form of cancer in women. 2-Deoxy-20-hydroxyecdysone with submicromolar IC₅₀ was identified as a result. The structure-activity relationship derived from the data from the in vitro proliferation assay showed that the hydroxyl group present at position C-2 of steroid core reduces the ecdysteroids' cytotoxicity against cancer cells.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11505650/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142494455","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":"Validation of the Enzyme-Linked ImmunoSpot Analytic Method for the Detection of Human IFN-γ from Peripheral Blood Mononuclear Cells in Response to the SARS-CoV-2 Spike Protein.","authors":"Laura E Carreto-Binaghi, Milton Nieto-Ponce, Andrea Palencia-Reyes, Rodolfo L Chávez-Domínguez, Jessica Blancas-Zaragoza, Pablo Franco-Mendoza, Montserrat A García-Ramos, Claudia I Hernández-Lázaro, Martha Torres, Claudia Carranza","doi":"10.3390/biom14101286","DOIUrl":"https://doi.org/10.3390/biom14101286","url":null,"abstract":"<p><p>COVID-19 vaccine evaluations are mainly focused on antibody analyses, but there is growing interest in measuring the cellular immune responses from the researchers evaluating these vaccines. The cellular responses to several COVID-19 vaccines have been studied using the enzyme-linked immunospot (ELISPOT) assay for IFN-γ. However, the ELISPOT assay is no longer used only for research purpose and so the performance of this assay must be validated. Since the bioanalytical validation of ELISPOT-IFN-γ is essential for evaluating the method's effectiveness and establishing confidence in a vaccine's immunogenicity, the present work validates the ELISPOT-IFN-γ assay's performance in determining the frequency of IFN-γ-producing cells after stimulation with the SARS-CoV-2 spike protein. The validation was performed in peripheral blood mononuclear cells from volunteers immunized with anti-COVID-19 vaccines. According to the findings, the LOD was 17 SFU and the LLOQ was 22 SFU, which makes the method highly sensitive and suitable for evaluating low levels of cellular responses. The procedure's accuracy is confirmed by the correlation coefficients for the spike protein and anti-CD3⁺, being 0.98 and 0.95, respectively. The repeatability and intermediate precision tests were confirmed to be reliable by obtaining a coefficient of variation of ≤25%. The results obtained in this validation enable the assay to be employed for studying antigen-specific cells and evaluating cellular responses to vaccines.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11506497/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142516287","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}