Physiological research最新文献

{"title":"Can Alpha-Pinene Prevent Methotrexate-Induced Cardiac and Hepatic Damage?","authors":"S Cirrik, G Hacioglu, E Kabartan, B Tezcan Yavuz, C Sirin Tomruk","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The effects of alpha-pinene (AP), a monoterpenoid, known for its antioxidant, anti-inflammatory, and anti-apoptotic properties, on methotrexate (MTX)-induced cardiac and hepatic damage were investigated in this study. Male Sprague-Dawley rats were divided into Control, Vehicle, AP, MTX, and AP+MTX groups (n=7). AP (50 mg/kg/day, 14 days) was applied subcutaneously in the AP and AP+MTX groups. MTX (20 mg/kg) was injected three days before sacrification. Serum CK-MB, troponin T, ALT, and AST levels, as well as cardiac and hepatic MDA, GSH, caspase-3, and p53 levels, were measured by ELISA. Histological changes in tissues were evaluated by scoring in terms of tissue damage and cellular degeneration parameters after hematoxylin-eosin staining. MTX caused significant increase in serum CK-MB, troponin T, ALT, and AST levels, hepatic and cardiac lipid peroxidation, GSH depletion, and caspase-3 level. However, tissue levels of p53 did not change significantly. MTX-induced histological deterioration was observed in both tissues. These MTX-induced changes were significantly reduced in the AP+MTX group. Present results show that MTX-induced cardiac and hepatic damage is prevented by AP pretreatment. This protection can be attributed to the antioxidant and anti-apoptotic properties of AP. Considering the importance of MTX in cancer treatment, AP appears to have highly promising potential as a cardioprotective and hepatoprotective agent in anti-tumoral therapy. Key words: MDA, GSH, Caspase-3, p53, Oxidative stress, Apoptosis.</p>","PeriodicalId":20235,"journal":{"name":"Physiological research","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11414590/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142293712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Impact of COVID-19 Third Dose Vaccination on the Magnitude of Antigen Specific T Cells in Kidney Transplant Patients.","authors":"E Girmanova, J Duskova, P Mrazova, M Fialova, O Viklicky, P Hruba","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Measuring T cell response can add information about antivirus immunity provided by antibody test results. The study evaluates the impact of a third mRNA COVID-19 vaccine dose on T cell response and antibody production in kidney transplant recipients (25 KTRs) versus healthy controls (26 Hc). Results show a significant rise in S-activated CD4+CD154+IFN?+TNF?+ double producer cells in both KTRs (p=0.025) and Hc (p=0.009) as well as increased spike antibody response in KTRs (p=0.00019) and Hc (p=3.10-8) third-month post-third dose. Moreover, the study revealed a drop in seronegative KTRs (non-responders) from 9/25 (36%) pre-third dose to 2/25 (7%) at 3 months post-third dose while 5/9 (56%) of non-responders post-second dose showed specific T cell responses. Notably, the third dose significantly improved seroconversion rates in both KTRs and Hc, although Hc individuals exhibited higher antibody levels. Key words: mRNA COVID-19 vaccine, T cells, SARS-CoV-2 antibodies, Kidney transplantation, mRNA vaccination.</p>","PeriodicalId":20235,"journal":{"name":"Physiological research","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11414591/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142293721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modern Perspective of Lactate Metabolism.","authors":"J Vavřička, P Brož, D Follprecht, J Novák, A Kroužecký","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Once considered a metabolic waste product, today it is considered an important signaling molecule continuously forming under aerobic conditions. Lactate, a molecule primarily known as a byproduct of glycolysis, has gained importance in recent years due to its multifaceted role in various biological processes. Misconceptions surrounding lactate have persisted for centuries, especially the belief that elevated lactate levels were solely a result of low oxygen levels shaped early understanding. However, current research challenges this view and expands our comprehension of lactate's various roles. Unfortunately, despite all of the mentioned above lactate is rooted in modern society as a deterrent word and many people do not know its value in the human body, let alone clinical implementations or physical performance. The main goal of this review is to refresh current knowledge regarding lactate research and spread the overall information among a professional society. Key words: Lactate, Lactate metabolism, Lactic acid, Disease metabolism, Lactate shuttle.</p>","PeriodicalId":20235,"journal":{"name":"Physiological research","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11414593/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142293719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Idiopathic Pulmonary Fibrosis: Review of Current Knowledge.","authors":"J Muri, B Durcová, R Slivka, A Vrbenská, M Makovická, P Makovický, J Škarda, P Delongová, V Kamarád, J Vecanová","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Idiopathic pulmonary fibrosis (IPF) is a severe and currently incurable disease that is associated with irreversible fibrotic remodeling of the lung parenchyma. Pathological remodeling of the lung leads to damage of the alveolo-capillary barrier. There is a reduction in the diffusing capacity of the lungs for respiratory gases. Later, changes in the mechanical properties of lung tissue occur - their compliance decreases and respiratory work increases. Impaired respiratory gases exchange with restrictive ventilatory failure lead to tissue hypoxia and muscle weakness. Progressive respiratory insufficiency develops. The triggers of fibrotic remodeling of the lung are currently unknown, as are the pathomechanisms that keep this process active. IPF can only be slowed pharmacologically, not reversed. It is therefore very important to start its treatment as soon as possible. Early detection of IPF patients requires a multidisciplinary approach. Diagnosis, treatment initiation, and monitoring in specialized centers offer the best chance of slowing disease progression, enhancing quality of life, and extending patient survival. In addition to antifibrotic therapy, good lifestyle management, maintenance of physical fitness and treatment of associated chronic diseases such as diabetes and cardiac comorbidities are important. Lung transplantation is an option for some patients with IPF. This is a challenging treatment modality, requiring close collaboration with transplant centers and expert selection of suitable candidates, influenced, among other things, by the availability of suitable donor lungs. Our article aims to provide current information about IPF, focusing on its functional consequences and clinical manifestation. We discuss the molecular and cellular mechanisms potentially involved in IPF development, as well as the morphological changes observed in lung biopsies and high-resolution computed tomography (HRCT) images. Finally, we summarize the existing treatment options. Key words: Idiopathic pulmonary fibrosis, Lung biopsy, HRCT, Antifibrotic therapy, Lung transplantation.</p>","PeriodicalId":20235,"journal":{"name":"Physiological research","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11414582/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142293717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Western Diet-Induced Nonalcoholic Fatty Liver Disease Mice Mimic the Key Transcriptomic Signatures Observed in Humans.","authors":"T Ishigure, T Sasase, M Tohma, K Uno, Y Toriniwa, T Saito, Y Saigo, K Edamura, K Miyajima, T Ohta","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease characterized by the accumulation of fat in the liver in the absence of excessive alcohol consumption or a secondary cause of hepatic steatosis. The prevalence of NAFLD is increasing worldwide and its management has become a public health concern. Animal models are traditionally used to elucidate disease mechanisms and identify potential drug targets; however, their translational aspects in human diseases have not been fully established. This study aimed to clarify the utility of animal models for translational research by assessing their relevance to human diseases using gene expression analysis. Weighted gene co-expression network analysis of liver tissues from Western diet (WD)-induced NAFLD mice was performed to identify the modules associated with disease progression. Moreover, the similarity of the gene co-expression network across species was evaluated using module preservation analysis. Nineteen disease-associated modules were identified. The brown module was positively associated with disease severity, and functional analyses indicated that it may be involved in inflammatory responses in immune cells. Moreover, the gene co-expression network of the brown module was highly preserved in human NAFLD liver gene expression datasets. These results indicate that WD-induced NAFLD mice have similar gene co-expression networks (especially genes associated with inflammatory responses) to humans and are thought to be a useful experimental tool for preclinical research on NAFLD. Keywords: Nonalcoholic fatty liver disease (NAFLD), Weighted gene co-expression network analysis (WGCNA), Western diet (WD).</p>","PeriodicalId":20235,"journal":{"name":"Physiological research","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11414584/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142293723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"First Application of Whole Genome Sequencing in Myelinated Retinal Nerve Fibers (MRNF).","authors":"E Scott Sills, C Harrity, H I Chu, J W Wang, S H Wood, S L Tan","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Genetic features are currently unknown in myelinated retinal nerve fibers (MRNF). For a 20-year-old asymptomatic female with unilateral MRNF, we performed whole genome sequencing (WGS) by standard workflow protocol to produce contiguous long-read sequences with Illumina DNA PCR-Free Prep. After tagmentation, libraries were sequenced on separate runs via NovaSeq 6000 platform at 2 x 150bp read length. Gene variants included rs2248799, rs2672589, rs7555070, rs247616_T and rs2043085_C all associated with an increased macular degeneration risk, and seven novel variants of uncertain significance. For optic disc enlargement, variants rs9988687_A, rs11079419_T, rs6787363 and rs10862708_A suggested an increased risk for this condition. In contrast, modeling revealed retinal detachment risk was reduced by variants identified at rs9651980_T, rs4373767_T, and rs7940691_T which were among five other previously unreported variants. WGS data placed proband at the 66th and 64th percentiles for disc anomaly and retinal detachment risk, respectively. Additionally, risk determined from 16 loci associated with age-related macular degeneration found the patient to be at the 18th percentile for this diagnosis (i.e., below average genetic predisposition). Fundoscopic findings showed mean RNFL thickness was lower with MRNF (77 OS vs. 96?m OD) and RNFL symmetry was impaired (43 %) but stable between 2020 and 2023. Rim area and cup volume were also substantially different (2.33 OS vs. 1.34mm2 OD, and 0.001 OS vs. 0.151mm3 OD, respectively). As the first known evaluation of MRNF via WGS, these data reveal a mixed picture with variants associated with different risks for potentially related ocular pathologies. In addition, we identify multiple new variants of unknown significance. Factors affecting gene expression in MRNF require further study. Key words: Whole genome sequencing, Retina, Myelination, Anatomy, Gene variants.</p>","PeriodicalId":20235,"journal":{"name":"Physiological research","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11414596/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142293715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Influence of Lipid Class Used for Omega-3 Fatty Acid Supplementation on Liver Fat Accumulation in MASLD.","authors":"I Sabinari, O Horakova, T Cajka, V Kleinova, M R Wieckowski, M Rossmeisl","doi":"10.33549/physiolres.935396","DOIUrl":"10.33549/physiolres.935396","url":null,"abstract":"<p><p>Metabolic dysfunction-associated steatotic liver disease (MASLD) occurs in subjects with obesity and metabolic syndrome. MASLD may progress from simple steatosis (i.e., hepatic steatosis) to steatohepatitis, characterized by inflammatory changes and liver cell damage, substantially increasing mortality. Lifestyle measures associated with weight loss and/or appropriate diet help reduce liver fat accumulation, thereby potentially limiting progression to steatohepatitis. As for diet, both total energy and macronutrient composition significantly influence the liver's fat content. For example, the type of dietary fatty acids can affect the metabolism of lipids and hence their tissue accumulation, with saturated fatty acids having a greater ability to promote fat storage in the liver than polyunsaturated ones. In particular, polyunsaturated fatty acids of n-3 series (omega-3), such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), have been intensively studied for their antisteatotic effects, both in preclinical animal models of obesity and hepatic steatosis and in overweight/obese patients. Their effects may depend not only on the dose and duration of administration of omega-3, or DHA/EPA ratio, but also on the lipid class used for their supplementation. This review summarizes the available evidence from recent comparative studies using omega-3 supplementation via different lipid classes. Albeit the evidence is mainly limited to preclinical studies, it suggests that phospholipids and possibly wax esters could provide greater efficacy against MASLD compared to traditional chemical forms of omega-3 supplementation (i.e., triacylglycerols, ethyl esters). This cannot be attributed solely to improved EPA and/or DHA bioavailability, but other mechanisms may be involved. Keywords: MASLD • Metabolic dysfunction-associated steatotic liver disease • NAFLD • Non-alcoholic fatty liver disease • n-3 polyunsaturated fatty acids.</p>","PeriodicalId":20235,"journal":{"name":"Physiological research","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11412347/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141627418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondrial Physiology of Cellular Redox Regulations.","authors":"P Ježek, A Dlasková, H Engstová, J Špačková, J Tauber, P Průchová, E Kloppel, O Mozheitova, M Jabůrek","doi":"10.33549/physiolres.935269","DOIUrl":"10.33549/physiolres.935269","url":null,"abstract":"<p><p>Mitochondria (mt) represent the vital hub of the molecular physiology of the cell, being decision-makers in cell life/death and information signaling, including major redox regulations and redox signaling. Now we review recent advances in understanding mitochondrial redox homeostasis, including superoxide sources and H2O2 consumers, i.e., antioxidant mechanisms, as well as exemplar situations of physiological redox signaling, including the intramitochondrial one and mt-to-cytosol redox signals, which may be classified as acute and long-term signals. This review exemplifies the acute redox signals in hypoxic cell adaptation and upon insulin secretion in pancreatic beta-cells. We also show how metabolic changes under these circumstances are linked to mitochondrial cristae narrowing at higher intensity of ATP synthesis. Also, we will discuss major redox buffers, namely the peroxiredoxin system, which may also promote redox signaling. We will point out that pathological thresholds exist, specific for each cell type, above which the superoxide sources exceed regular antioxidant capacity and the concomitant harmful processes of oxidative stress subsequently initiate etiology of numerous diseases. The redox signaling may be impaired when sunk in such excessive pro-oxidative state.</p>","PeriodicalId":20235,"journal":{"name":"Physiological research","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11412358/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140855885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolomics and Lipidomics for Studying Metabolic Syndrome: Insights into Cardiovascular Diseases, Type 1 & 2 Diabetes, and Metabolic Dysfunction-Associated Steatotic Liver Disease.","authors":"S Rakusanova, T Cajka","doi":"10.33549/physiolres.935443","DOIUrl":"10.33549/physiolres.935443","url":null,"abstract":"<p><p>Metabolomics and lipidomics have emerged as tools in understanding the connections of metabolic syndrome (MetS) with cardiovascular diseases (CVD), type 1 and type 2 diabetes (T1D, T2D), and metabolic dysfunction-associated steatotic liver disease (MASLD). This review highlights the applications of these omics approaches in large-scale cohort studies, emphasizing their role in biomarker discovery and disease prediction. Integrating metabolomics and lipidomics has significantly advanced our understanding of MetS pathology by identifying unique metabolic signatures associated with disease progression. However, challenges such as standardizing analytical workflows, data interpretation, and biomarker validation remain critical for translating research findings into clinical practice. Future research should focus on optimizing these methodologies to enhance their clinical utility and address the global burden of MetS-related diseases.</p>","PeriodicalId":20235,"journal":{"name":"Physiological research","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11412346/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142111208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic Pathways of Acylcarnitine Synthesis.","authors":"J Brejchova, K Brejchova, O Kuda","doi":"10.33549/physiolres.935261","DOIUrl":"10.33549/physiolres.935261","url":null,"abstract":"<p><p>Acylcarnitines are important markers in metabolic studies of many diseases, including metabolic, cardiovascular, and neurological disorders. We reviewed analytical methods for analyzing acylcarnitines with respect to the available molecular structural information, the technical limitations of legacy methods, and the potential of new mass spectrometry-based techniques to provide new information on metabolite structure. We summarized the nomenclature of acylcarnitines based on historical common names and common abbreviations, and we propose the use of systematic abbreviations derived from the shorthand notation for lipid structures. The transition to systematic nomenclature will facilitate acylcarnitine annotation, reporting, and standardization in metabolomics. We have reviewed the metabolic origins of acylcarnitines important for the biological interpretation of human metabolomic profiles. We identified neglected isomers of acylcarnitines and summarized the metabolic pathways involved in the synthesis and degradation of acylcarnitines, including branched-chain lipids and amino acids. We reviewed the primary literature, mapped the metabolic transformations of acyl-CoAs to acylcarnitines, and created a freely available WikiPathway WP5423 to help researchers navigate the acylcarnitine field. The WikiPathway was curated, metabolites and metabolic reactions were annotated, and references were included. We also provide a table for conversion between common names and abbreviations and systematic abbreviations linked to the LIPID MAPS or Human Metabolome Database.</p>","PeriodicalId":20235,"journal":{"name":"Physiological research","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11412349/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140944588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}