Biomolecules最新文献

{"title":"AMPK Signaling Axis-Mediated Regulation of Lipid Metabolism: Ameliorative Effects of Sodium Octanoate on Intestinal Dysfunction in Hu Sheep.","authors":"Huimin Zhang, Shuo Yan, Zimeng Ma, Ruilin Du, Xihe Li, Siqin Bao, Yongli Song","doi":"10.3390/biom15050707","DOIUrl":"10.3390/biom15050707","url":null,"abstract":"<p><p>At the present stage, heavy metal pollution, led by environmental exposure to cadmium (Cd), has caused incalculable losses in animal husbandry. The potential value of caprylic acid as a medium- and long-chain fatty acid with a unique role in regulating lipid metabolism has attracted much attention. Our previous study found that octanoic acid levels were significantly reduced under Cd-exposed conditions in Hu Sheep, on the basis of which we investigated the protective effect of sodium octanoate, a derivative of octanoic acid, against Cd exposure in Hu Sheep in the present study. In this study, an animal model of Cd exposure in Hu Sheep was established. Comprehensive assessment of Cd-induced intestinal injury using hematoxylin and eosin (H&E) staining, immunostaining and carried out in-depth analyses combined with lipid metabolomics and transcriptomics. The results showed that Cd exposure triggered intestinal inflammation, barrier function damage and oxidative stress imbalance. Lipid metabolomics analysis showed that Cd exposure severely disrupted lipid metabolic processes, especially the glycerophospholipid metabolic pathway, suggesting that lipid metabolic disorders are closely related to intestinal injury. Notably, sodium octanoate could partially reverse the lipid metabolism abnormality by regulating the Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) signaling pathway, effectively alleviating the Cd toxicity, which provides a brand-new prevention and control strategy for Cd-induced intestinal injury in the livestock industry pollution-mediated disease.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 5","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12108909/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144156536","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":"The Association Between Myokines, Inflammation, and Nutritional Status in Patients with Multiple Sclerosis.","authors":"Natalia Mogiłko, Sylwia Małgorzewicz","doi":"10.3390/biom15050703","DOIUrl":"10.3390/biom15050703","url":null,"abstract":"<p><strong>Background: </strong>Recent studies indicate that in progressive multiple sclerosis (MS)-an inflammatory and degenerative disease of the central nervous system-the biological pathways associated with these effects remain poorly understood. Changes in body weight, whether presenting as overweight or underweight, as well as alterations in adipose and muscle tissue, together with chronic inflammation, may contribute to the disease and influence its course.</p><p><strong>Objective: </strong>This case-control study aimed to measure inflammatory markers and myokine levels (myostatin and irisin), brain-derived neurotrophic factor (BDNF), and IL-6 in the serum of patients with multiple sclerosis and healthy control and assess whether the myokines and cytokines are associated with nutritional status.</p><p><strong>Methods: </strong>The study included 92 MS patients and 75 healthy volunteers. Nutritional status was assessed using the NRS (Nutritional Risk Screening) 2002 and GLIM (Global Leadership Initiative on Malnutrition) criteria. The risks of malnutrition or malnutrition were diagnosed based on ESPEN recommendations. Body composition analysis was performed using the BIA method with the InBody 120 analyzer. Routine laboratory parameters (albumin, lipidogram) were measured. Myostatin, irisin, BDNF, IL-6, and hsCRP were measured using ELISA methods. Statistical analysis was conducted using Statistica 13.0 software. Comparisons between the two groups were conducted using Student's <i>t</i>-test for normally distributed variables and the Mann-Whitney U test for non-normally distributed variables; the differences between groups were calculated using either ANOVA or the Kruskal-Wallis test. Post hoc analysis by the Bonferroni method was applied.</p><p><strong>Results: </strong>In the MS group, high risks of malnutrition (69.0%) and malnutrition (14.0%) were observed. A statistically significant correlation was found between malnutrition (GLIM) and s-albumin (R = 0.2; <i>p</i> < 0.05) and hsCRP (R = 0.23; <i>p</i> < 0.05). The MS patient group displayed significantly lower levels of irisin, higher levels of hsCRP, and lower s-albumin compared to healthy volunteers. Malnourished patients with MS exhibited significantly lower irisin levels, as well as higher hsCRP in comparison to MS patients who were at risk or well nourished. The levels of myostatin, BDNF, and IL6 did not differ depending on nutritional status. Irisin correlated with hsCRP (R Spearman = -0.5; <i>p</i> = 0.01).</p><p><strong>Conclusions: </strong>Our findings highlight the interplay between chronic inflammation, nutritional status, and myokines level in multiple sclerosis.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 5","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12110006/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144156607","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":"Role of Tumor Necrosis Factor in Tuberculosis.","authors":"Fedor D Kireev, Julia A Lopatnikova, Alina A Alshevskaya, Sergey V Sennikov","doi":"10.3390/biom15050709","DOIUrl":"10.3390/biom15050709","url":null,"abstract":"<p><p>Tumor necrosis factor (TNF) is a key immunoregulatory cytokine with a dual role in the host response to <i>Mycobacterium tuberculosis</i>. While essential for granuloma formation, macrophage activation, and containment of latent infection, TNF can also contribute to tissue damage and immune pathology. This review systematically analyzes over 300 peer-reviewed studies published between 1980 and 2024, highlighting the molecular and cellular mechanisms of TNF action in tuberculosis (TB). Particular attention is given to TNF receptor signaling pathways, the balance between protective and pathological immune responses, and the modulation of TNF activity during anti-TNF therapy in patients with autoimmune diseases. We discuss how different TNF inhibitors vary in their capacity to interfere with host defense mechanisms, with monoclonal antibodies carrying a higher reactivation risk than receptor-based agents. To enhance conceptual clarity, we provide newly developed schematic representations that integrate current knowledge on TNF-driven immune dynamics, including its interaction with other cytokines, effects on granuloma stability, and role in intracellular bacterial control. Understanding the pleiotropic functions of TNF in tuberculosis pathogenesis is crucial for developing safe immunomodulatory strategies and optimizing the clinical management of patients at risk of latent TB reactivation.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 5","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12108764/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144156551","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":"Cell-Penetrating Peptide Based on Myosin Phosphatase Target Subunit Sequence Mediates Myosin Phosphatase Activity.","authors":"Andrea Kiss, Mohamad Mahfood, Zsófia Bodogán, Zoltán Kónya, Bálint Bécsi, Ferenc Erdődi","doi":"10.3390/biom15050705","DOIUrl":"10.3390/biom15050705","url":null,"abstract":"<p><p>Myosin phosphatase (MP) holoenzyme consists of protein phosphatase-1 (PP1) catalytic subunit (PP1c) associated with myosin phosphatase target subunit-1 (MYPT1) and it plays an important role in mediating the phosphorylation of the 20 kDa light chain (MLC20) of myosin, thereby regulating cell contractility. The association of MYPT1 with PP1c increases the phosphatase activity toward myosin; therefore, disrupting/dissociating this interaction may result in inhibition of the dephosphorylation of myosin. In this study, we probed how MYPT1^32-58 peptide including major PP1c interactive regions coupled with biotin and cell-penetrating TAT sequence (biotin-TAT-MYPT1) may influence MP activity. Biotin-TAT-MYPT1 inhibited the activity of MP holoenzyme and affinity chromatography as well as surface plasmon resonance (SPR) binding studies established its stable association with PP1c. Biotin-TAT-MYPT1 competed for binding to PP1c with immobilized GST-MYPT1 in SPR assays and it partially relieved PP1c inhibition by thiophosphorylated (on Thr696 and Thr853) MYPT1. Moreover, biotin-TAT-MYPT1 dissociated PP1c from immunoprecipitated PP1c-MYPT1 complex implying its holoenzyme disrupting ability. Biotin-TAT-MYPT1 penetrated into A7r5 smooth muscle cells localized in the cytoplasm and nucleus and exerted inhibition on MP with a parallel increase in MLC20 phosphorylation. Our results imply that the biotin-TAT-MYPT1 peptide may serve as a specific MP regulatory cell-penetrating peptide as well as possibly being applicable to further development for pharmacological interventions.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 5","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12110079/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144156589","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 Novel Ashwagandha (<i>Withania somnifera</i>) Formulation Mitigates Sleep Deprivation-Induced Cognitive Impairment and Oxidative Stress in a Rat Model.","authors":"Besir Er, Busra Ozmen, Emre Sahin, Cemal Orhan, Nurhan Sahin, Abhijeet A Morde, Muralidhara Padigaru, Kazim Sahin","doi":"10.3390/biom15050710","DOIUrl":"10.3390/biom15050710","url":null,"abstract":"<p><p>Ashwagandha (<i>Withania somnifera</i>) is a well-known adaptogenic herb traditionally used to enhance sleep quality and mitigate stress-induced cognitive decline. This study investigated the effects of different doses of ashwagandha root extract (AE) formulations on cognitive function, oxidative stress, and neuronal plasticity in a rat model of sleep deprivation (SD). Forty-nine rats were randomly assigned to seven groups: control, wide platform (WP), SD, SD + A1 (15 mg/kg AE 1.5%), SD + A2 (30 mg/kg AE 1.5%), SD + A3 (5.5 mg/kg AE 8.0%), and SD + A4 (11 mg/kg AE 8.0%). The extract was administered orally for four weeks. SD induced via a modified wide platform model significantly impaired spatial memory, increased oxidative stress, and suppressed GABA receptor activity. Treatment with all AE doses, except 15 mg/kg AE 1.5%, considerably reduced serum corticosterone (12% for SD + A2, 15% for SD + A3, and 32% for SD + A4), CRH (11% for SD + A2, 14% for SD + A3, and 17% for SD + A4), ACTH (22% for SD + A2, 26% for SD + A3, and 38% for SD + A4), and MDA levels (31% for SD + A2, 34% for SD + A3, and 46% for SD + A4) (<i>p</i> < 0.05). All doses improved antioxidant enzyme activity and memory performance, while AE 8.0% doses notably increased serotonin (19% for SD + A3 and 33% for SD + A4) and dopamine levels (40% for SD + A3 and 50% for SD + A4). Moreover, AE treatment enhanced markers of neuronal plasticity and partially improved GABAergic function. These findings suggest that AE formulations, particularly at higher concentrations, exert neuroprotective effects against SD-induced cognitive impairment by modulating oxidative stress, neurotransmitter balance, and neuroplasticity, indicating their potential application in managing stress-related neurological disorders.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 5","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12109121/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144156447","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":"Robust Method for Confidence Interval Estimation in Outlier-Prone Datasets: Application to Molecular and Biophysical Data.","authors":"Victor V Golovko","doi":"10.3390/biom15050704","DOIUrl":"10.3390/biom15050704","url":null,"abstract":"<p><p>Estimating confidence intervals in small or noisy datasets is a recurring challenge in biomolecular research, particularly when data contain outliers or exhibit high variability. This study introduces a robust statistical method that combines a hybrid bootstrap procedure with Steiner's most frequent value (MFV) approach to estimate confidence intervals without removing outliers or altering the original dataset. The MFV technique identifies the most representative value while minimizing information loss, making it well suited for datasets with limited sample sizes or non-Gaussian distributions. To demonstrate the method's robustness, we intentionally selected a dataset from outside the biomolecular domain: a fast-neutron activation cross-section of the ¹⁰⁹Ag(n, 2n)^108mAg reaction from nuclear physics. This dataset presents large uncertainties, inconsistencies, and known evaluation difficulties. Confidence intervals for the cross-section were determined using a method called the MFV-hybrid parametric bootstrapping (MFV-HPB) framework. In this approach, the original data points were repeatedly resampled, and new values were simulated based on their uncertainties before the MFV was calculated. Despite the dataset's complexity, the method yielded a stable MFV estimate of 709 mb with a 68.27% confidence interval of [691, 744] mb, illustrating the method's ability to provide interpretable results in challenging scenarios. Although the example is from nuclear science, the same statistical issues commonly arise in biomolecular fields, such as enzymatic kinetics, molecular assays, and diagnostic biomarker studies. The MFV-HPB framework provides a reliable and generalizable approach for extracting central estimates and confidence intervals in situations where data are difficult to collect, replicate, or interpret. Its resilience to outliers, independence from distributional assumptions, and compatibility with small-sample scenarios make it particularly valuable in molecular medicine, bioengineering, and biophysics.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 5","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12109080/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144156572","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":"Examining the Effects of the RUNX1 p.Leu43Ser Variant on FPD/AML Phenotypes Using a CRISPR/Cas9-Generated Knock-In Murine Model.","authors":"Ana Marin-Quilez, Ignacio García-Tuñón, Rocío Benito, José Luis Ordoñez, Lorena Díaz-Ajenjo, Ana Lama-Villanueva, Carmen Guerrero, Jesús Pérez-Losada, José Ramón González-Porras, Jesús María Hernández-Rivas, Mónica Del Rey, José María Bastida","doi":"10.3390/biom15050708","DOIUrl":"10.3390/biom15050708","url":null,"abstract":"<p><p>Germline heterozygous variants in <i>RUNX1</i> lead to Familial Platelet Disorder with Myeloid Leukemia Predisposition (FPD/AML). Cellular and/or animal models are helpful to uncovering the role of a variant in disease progression. Twenty-five mice per genotype (RUNX1^WT/WT, RUNX1^WT/L43S, RUNX1^L43S/L43S), previously generated by CRISPR/Cas9, and nine sub-lethally irradiated mice per genotype were investigated. Peripheral blood (PB), bone marrow (BM), and spleen samples were analyzed by flow cytometry and histopathology. Deregulated genes were analyzed by RNA-seq in BM. An aberrant myeloid Mac1⁺Sca1⁺ckit^- population in the PB, BM, and spleen of two homozygous and one heterozygous mouse was observed, as well as BM hypercellularity. No Mac1⁺Sca1⁺ckit^- cells were detected in any RUNX1^WT/WT mice. Moreover, the spleen of both homozygous mice showed destruction of the white/red pulp and the presence of apoptotic cells. The aberrant population was also detected in four irradiated mice, two heterozygous and two homozygous, in their PB, BM, and spleen. RNA-seq studies showed 698 genes significantly deregulated in the three non-irradiated Mac1⁺Sca1⁺ckit^- mice vs. six healthy mice, highlighting the alteration of genes involved in apoptosis and DNA repair. These results indicate that the homozygous form of the variant p.Leu43Ser may contribute to the pathogenesis of aberrant cells.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 5","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12109519/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144156710","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":"Molecular and Biophysical Perspectives on Dormancy Breaking: Lessons from Yeast Spore.","authors":"Keiichiro Sakai, Yohei Kondo, Kazuhiro Aoki, Yuhei Goto","doi":"10.3390/biom15050701","DOIUrl":"10.3390/biom15050701","url":null,"abstract":"<p><p>Dormancy is a physiological state that enables cells to survive under adverse conditions by halting their proliferation while retaining the capacity to resume growth when conditions become favorable. This remarkable transition between dormant and proliferative states occurs across a wide range of species, including bacteria, fungi, plants, and tardigrades. Among these organisms, yeast cells have emerged as powerful model systems for elucidating the molecular and biophysical principles governing dormancy and dormancy breaking. In this review, we provide a comprehensive summary of current knowledge on the molecular mechanisms underlying cellular dormancy, with particular focus on the two major model yeasts: <i>Saccharomyces cerevisiae</i> and <i>Schizosaccharomyces pombe</i>. Recent advances in multifaceted approaches-such as single-cell RNA-seq, proteomic analysis, and live-cell imaging-have revealed dynamic changes in gene expression, proteome composition, and viability. Furthermore, insights into the biophysical properties of the cytoplasm have offered new understanding of dormant cell regulation through changes in cytoplasmic fluidity. These properties contribute to both the remarkable stability of dormant cells and their capacity to exit dormancy upon environmental cues, deepening our understanding of fundamental cellular survival strategies across diverse species.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 5","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12109108/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144156565","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":"Melatonin Secretion and Impacts of Training and Match Schedules on Sleep Quality, Recovery, and Circadian Rhythms in Young Professional Football Players.","authors":"Antonio Almendros-Ruiz, Javier Conde-Pipó, Paula Aranda-Martínez, Jesús Olivares-Jabalera, Darío Acuña-Castroviejo, Bernardo Requena, José Fernández-Martínez, Miguel Mariscal-Arcas","doi":"10.3390/biom15050700","DOIUrl":"10.3390/biom15050700","url":null,"abstract":"<p><p>Modern elite football is becoming increasingly physically demanding, often requiring training and matches to be played at night. This schedule may disrupt circadian rhythms and melatonin secretion, thereby impairing sleep and recovery. This study investigated the effects of training time on melatonin secretion, circadian phase markers, and sleep parameters in elite youth soccer players. Forty male players (aged 16-18 years) from an elite Spanish youth football club were studied. Two groups followed the same training program but trained either in the morning (MT) or in the evening (ET). Salivary melatonin was measured at six time points to determine the mean levels, dim light melatonin onset (DLMO), amplitude, and acrophase. Chronotype, sleep quality (PSQI), and daytime sleepiness (ESS) were assessed using validated questionnaires. Dietary intake and anthropometric variables were also recorded. The MT group had higher mean melatonin levels (<i>p</i> = 0.026) and earlier DLMO (<i>p</i> = 0.023) compared to the ET group. Sleep quality was significantly better in the MT group (<i>p</i> < 0.001), despite shorter sleep duration (<i>p</i> = 0.014). No major differences in diet or anthropometry were observed. The chronotype had a secondary effect on the circadian markers. Evening training is associated with alterations in melatonin rhythms and reduced sleep quality, possibly due to light-induced chronodisruption. These findings highlight the importance of training timing as a modifiable factor in the chronobiology and recovery of athletes. Incorporating circadian principles into training schedules may optimize resting time and thus performance and long-term health in athletes.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 5","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12109335/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144156517","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":"Genetic Polymorphism of <i>CYP2R1</i>, <i>CYP27A1</i>, <i>CYP27B1</i>, and Vitamin D Metabolites Plasma Levels in Patients with Cardiovascular Disease: A Pilot Study.","authors":"Mohamed Abouzid, Łukasz Kruszyna, Dominika Kaczmarek, Leonid Kagan, Aniceta Ada Mikulska-Sauermann, Dorota Filipowicz, Matylda Resztak, Franciszek K Główka, Marta Karaźniewicz-Łada","doi":"10.3390/biom15050699","DOIUrl":"10.3390/biom15050699","url":null,"abstract":"<p><p>The active form of vitamin D, calcitriol (1,25(OH)₂D₃), is produced from 25(OH)D₃ via enzymes encoded by <i>CYP2R1</i>, <i>CYP27A1</i>, and <i>CYP27B1</i>. Polymorphisms in these genes may alter vitamin D metabolism and increase cardiovascular disease risk. This preliminary study investigated these polymorphisms in 27 patients with cardiovascular disease and 26 healthy volunteers using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP), while measuring 25(OH)D₃ and 1,25(OH)₂D₃ concentrations by UPLC-MS/MS and ELISA, respectively. Among patients, those with the GT genotype of <i>rs10877012</i> (<i>CYP27B1</i>) had higher 25(OH)D₃ levels compared to other genotypes. Additionally, this polymorphism was associated with lower 1,25(OH)₂D₃ in TT homozygotes, suggesting reduced <i>CYP27B1</i> activity. Furthermore, the TT genotype of <i>rs6709815</i> (<i>CYP27A1</i>) was three times more prevalent in cardiac patients than in healthy controls, possibly indicating increased susceptibility to the disease. Although these findings suggest a genetic influence on vitamin D metabolism in cardiovascular disease, larger and more comprehensive studies are needed to confirm these associations.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 5","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12109444/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144156476","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}