Physiological research最新文献

{"title":"Bruton's Tyrosine Kinase: A Potential Novel Target for Neurological Disorders.","authors":"D Das, A Ghosh, D Greco, D Michaličková, O Slanař","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Bruton's tyrosine kinase (BTK) is a crucial part of the B-cell receptor signaling pathway that has been extensively studied in various types of malignancies. Recent studies have extended our knowledge on its role in metabolism as well as neurological disorders. It may play an important role in the pathophysiology of neurological diseases, such as multiple sclerosis, Alzheimer's disease, brain injury, and several others. Activation of inflammasomes, mainly NLRP3, is one of the core mechanisms by which it promotes inflammation in the brain related to aging and diseases. In this paper, we provide an overview of the less explored roles of BTK in several brain diseases and discuss the potential of its inhibition to become a therapeutic target for neurological diseases.</p>","PeriodicalId":20235,"journal":{"name":"Physiological research","volume":"74 2","pages":"233-248"},"PeriodicalIF":1.9,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12148142/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144161729","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":"Thyroid-Stimulating Hormone: An Important Target for the Prevention of Nonalcoholic Fatty Liver Disease.","authors":"Z Wang, H Wang, H Sun","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Non-alcoholic fatty liver disease (NAFLD) is one of the leading causes of cirrhosis and liver cancer. Its global prevalence increases annually, significantly affecting quality of life. Only a few patients manage to alleviate NAFLD through lifestyle modifications. The pathogenic mechanisms and therapeutic targets of this disease remain inadequately explored. In recent years, many studies highlighted a close relationship between the thyroid-stimulating hormone (TSH) and NAFLD. TSH has been shown to promote fat accumulation in the liver by participating in the ab initio synthesis, uptake and secretion of lipids. Moreover, TSH exacerbates hepatocyte inflammation and fibrosis by inducing endoplasmic reticulum stress and promoting the release of inflammatory factors. Although some of the conclusions remain controversial and are subject to debate, exploring the connection and possible pathways between TSH and NAFLD is crucial. Such research could advance early clinical prevention and intervention strategies, thereby reducing the incidence of severe NAFLD-associated comorbidities. Therefore, this review aims to summarize currently available evidence on the association between TSH and NAFLD focusing on the following objectives: elucidating the relationship between TSH and NAFLD; TSH may be a potential target for NAFLD prevention; exploring potential molecular targets that could block TSH-mediated promotion of NAFLD.</p>","PeriodicalId":20235,"journal":{"name":"Physiological research","volume":"74 2","pages":"175-187"},"PeriodicalIF":1.9,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12148143/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144161792","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":"Berberine Exerts Neuroprotective Effects in Alzheimer's Disease by Switching Microglia M1/M2 Polarization Through PI3K-AKT Signaling.","authors":"Y Hu, P Zhang, X Wang","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Berberine (BBR), a small molecule protoberberine isoquinoline alkaloid, is easy to cross the blood-brain barrier and is a potential drug for neurodegenerative diseases. Here, we explored the role and molecular mechanism of BBR in Alzheimer's disease (AD) progression. Weighted gene co-expression network analysis (WGCNA) was conducted to determine AD pathology-associated gene modules and differentially expressed genes (DEGs) were also identified. GO and KEGG analyses were performed for gene function and signaling pathway annotation. Cell counting kit-8 (CCK8) assay was applied to analyze cell viability. Immunofluorescence (IF) staining assay was conducted to measure the levels of polarization markers. The production of inflammatory cytokines was analyzed by enzyme-linked immunosorbent assay (ELISA). Reactive oxygen species (ROS) level and mitochondrial membrane potential (MMP) were detected using a ROS detection kit and a MMP Detection Kit (JC-1), respectively. AD pathology-associated DEGs were applied for GO function annotation and KEGG enrichment analysis, and the results uncovered that AD pathology was related to immune and inflammation. Lipopolysaccharide (LPS) exposure induced the M1 phenotype of microglia, and BBR suppressed LPS-induced M1 polarization and induced microglia toward M2 polarization. Through co-culture of microglia and neuronal cells, we found that BBR exerted a neuro-protective role by attenuating the injury of LPS-induced HMC3 on SH-SY5Y cells. Mechanically, BBR switched the M1/M2 phenotypes of microglia by activating PI3K-AKT signaling. In summary, BBR protected neuronal cells from activated microglia-mediated neuro-inflammation by switching the M1/M2 polarization in LPS-induced microglia via activating PI3K-AKT signaling. Key words Alzheimer's Disease, Berberine, Microglia polarization, Neuroinflammation, PI3K-AKT signaling.</p>","PeriodicalId":20235,"journal":{"name":"Physiological research","volume":"74 1","pages":"129-140"},"PeriodicalIF":1.9,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11995938/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143693111","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 Role of Mdivi-1 in Reducing Mitochondrial Fission via the NF-kappaB/JNK/SIRT3 Signaling Pathway in Acute Kidney Injury.","authors":"X-Y Gou, Y Li, X-P Fan","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>To explore the effects and underlying mechanisms of Mdivi-1 on three common clinical models of acute kidney injury (AKI). Three common AKI cell models were constructed, classified into the control group (human renal tubular epithelial cells [HK-2] cells), the Iohexol group (HK-2 cells treated with Iohexol), the Genta group (HK-2 cells treated with Gentamicin), and the Cis group (HK-2 cells treated with Cisplatin). To explore the optimal protective concentration of Mdivi-1 for each AKI cell model, the experimental design consisted of the following seven groups: the control group (HK-2 cells cultured in medium), three injury groups (HK-2 cells subjected to Iohexol, Gentamicin, or Cisplatin), and the corresponding protection groups (with a certain concentration of Mdivi-1 added to each injury group). Cellular survival and apoptosis, reactive oxygen species (ROS) levels, and the expression of recombinant Sirtuin 3 (SIRT3) in each group were measured. Mitochondrial fission and fusion dynamics in cells were observed under an electron microscope. To explore relevant pathways, the changes in relevant pathway proteins were analyzed through Western blotting. The half maximal inhibitory concentration (IC50) values were 150.06 mgI/ml at 6 h in the Iohexol group, 37.88 mg/ml at 24 h in the Gentamicin group, and 13.48 microM at 24 h in the Cisplatin group. Compared with the control group, the three injury groups showed increased cell apoptosis rates and higher expressions of apoptotic proteins in HK-2 cells, with an accompanying decrease in cell migration. After the addition of corresponding concentrations of Mdivi-1, the optimal concentrations were 3 µM in the Iohexo-3 group, 1 microM in the Genta-1 group, and 5 µM in the Cis-5 group, HK-2 cells showed the highest survival rate, reduced apoptosis, decreased mitochondrial ROS and SIRT3 expression, and reduced mitochondrial fission and autophagy when compared with each injury group. Further verification with Western blot analysis after the addition of Mdivi-1 revealed a reduction in the expressions of mitochondrial fission proteins DRP1, Nrf2, SIRT3, Caspase-3, Jun N-terminal Kinase (JNK)/P-JNK, NF-kappaB, Bcl2, and autophagic protein P62, as well as reduced ROS levels. Mdivi-1 had protective effects on the three common AKI cell models by potentially reducing mitochondrial fission in cells and inhibiting the production of ROS through the mediation of the NF- B/JNK/SIRT3 signaling pathway, thereby exerting protective effects. Key words AKI, Cisplatin, Gentamicin, Iohexol, Mdivi-1.</p>","PeriodicalId":20235,"journal":{"name":"Physiological research","volume":"74 1","pages":"79-92"},"PeriodicalIF":1.9,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11995932/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692917","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":"Utilizing Hyperbaric Oxygen Therapy to Improve Cognitive Function in Patients With Alzheimer's Disease by Activating Autophagy-Related Signaling Pathways.","authors":"B Li, H Li, H Chen, Y Sui, J Zeng, X Lin, Q Fan, Z Song","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>To investigate the impact of hyperbaric oxygen therapy (HBOT) on the cognitive function of mice with Alzheimer's disease (AD), while also identifying the cellular pathways associated with autophagy involved in the treatment. Twenty-four APP/PSl double transgenic mice were randomly assigned to either Group A or Group B, while another 24 C57 mice were randomly allocated to Group C or Group D. HBOT was administered to mice in Group B and Group D, and the Morris water maze test was used to assess changes in mice behavior. Histological examination using hematoxylin and eosin staining was conducted to observe pathological alterations in the hippocampus of the mice brain tissue. Polymerase chain reaction (PCR) was employed to analyze autophagy-related gene pathways in the hippocampus of the mice. Following HBOT, mice in Group B exhibited a significant reduction in escape latency and a notable increase in residence time within the target quadrant compared with Group A (P<0.05), as well as Group C and Group D (P<0.01). The hippocampal neurons in Group A and Group B mice exhibited disorganized arrangements, characterized by pyknosis and margination. Conversely, neurons in Group C displayed orderly arrangements, retaining intact structures with round nuclei demonstrating clear nuclear staining and normal morphology. The cellular morphology of mice in Group D remained unaffected. PCR analysis revealed no notable disparity in autophagy-related gene expression between Group A and Group C. However, the expression levels of five genes including Tgfb1, Mapk14, Bid, Atg7, and Akt1, were significantly elevated in Group B compared to Group A. HBOT has the potential to improve the cognitive function in mice modeled with AD. This improvement of cognitive function appears to be mediated by the up-regulation of autophagy-related genes, specifically Tgfb1, Mapk14, Bid, Atg7, and Akt1. These results indicate that HBOT may offer a therapeutic strategy for treating AD by enhancing autophagy mechanisms. Key words Alzheimer's disease, Autophagy, Hyperbaric oxygen, Morris water maze, PCR.</p>","PeriodicalId":20235,"journal":{"name":"Physiological research","volume":"74 1","pages":"141-147"},"PeriodicalIF":1.9,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11995944/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692926","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":"WITHDRAWAL Monitoring of Caffeine Consumption Effect on Skin Blood Properties by Diffuse Reflectance Spectroscopy.","authors":"Matija Milanic, Rok Hren, Jost Stergar, Urban Simoncic","doi":"10.33549/physiolres.930000.74.161","DOIUrl":"10.33549/physiolres.930000.74.161","url":null,"abstract":"<p><p>Matija MILANIC1,2, Rok HREN1,3,4, Jost STERGAR1,2, Urban SIMONCIC1,2 1Faculty of Mathematics and Physics, University of Ljubljana, Ljubljana, Republic of Slovenia, 2Jožef Stefan Institute, Ljubljana, Republic of Slovenia, 3Institute of Mathematics, Physics, and Mechanics, Ljubljana, Republic of Slovenia, 4Syreon Research Institute, Budapest, Hungary Physiol Res 2024 Mar 11;73(1):47-56. doi: 10.33549/physiolres.935138. PMID: 38466004 This paper has been retracted on the base of author´s request.</p>","PeriodicalId":20235,"journal":{"name":"Physiological research","volume":"74 1","pages":"161"},"PeriodicalIF":1.9,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11995939/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692929","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":"Phytochemical Screening and Monitoring of Intercellular Changes in Murine Leydig Cells After the Treatment of Trigonella foenum-graecum L. Microgreens In Vitro.","authors":"T Jambor, Z Goc, L Zuscikova, H Greifova, A Kovacik, E Kovacikova, M Pec, N Lukac","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The objective of our in vitro study was to quantify the biochemical profile where the total polyphenol, flavonoid and phenolic acid content was determined. The antioxidant potential of microgreen extract from Trigonella foenum-graecum L., was measured molybdenum reducing power assay. Specifically, the study assessed parameters such as metabolic activity (AlamarBlueTM assay), membrane integrity (CFDA-AM assay), mitochondrial potential (JC-1 assay), as well as reactive oxygen species generation (NBT assay). In addition, the steroid hormone release in TM3 murine Leydig cells after 12 h and 24 h exposures were quantified by enzyme-linked immunosorbent assay. The gained results indicate the highest value in total flavonoid content (182.59+/-2.13 mg QE) determination, supported by a significant (108.25+/-1.27 mg TE) antioxidant activity. The effects on metabolic activity, cell membrane integrity, and mitochondrial membrane potential were found to be both time- and dose-dependent. Notably, a significant suppression in reactive oxygen species generation was confirmed at 150, 200 and 250 microg/ml after 24 h exposure. In addition, progesterone and testosterone release was stimulated up to 250 microg/ml dose of Trigonella, followed by a decline in both steroid production at 300 and 1000 microg/ml. Our results indicate, that Trigonella at lower experimental doses (up to 250 microg/ml) may positively affect majority of monitored cell parameters in TM3 Leydig cells. Overleaf, increasing experimental doses may negatively affect the intracellular parameters already after 12 h of in vitro exposure. Key words Microgreens, Trigonella foenum-graecum L., Fenugreek, Leydig cells, Male reproduction.</p>","PeriodicalId":20235,"journal":{"name":"Physiological research","volume":"74 1","pages":"115-128"},"PeriodicalIF":1.9,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11995942/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692898","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 Structure and Functional Changes of Thyroid in Severe Acute Pancreatitis Rats.","authors":"B Yang, H Qiao, Y Liu, X Wang, W Peng","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Severe acute pancreatitis (SAP) is associated with metabolic disorders, hypocalcemia, and multiple organ failure. The objective of this study was to investigate changes in thyroid ultrastructure and function in rats with SAP and to provide a theoretical basis for the clinical treatment of thyroid injury in patients with SAP. 64 male SPF Wistar rats were randomly divided into the SAP group and the control group. Pancreatic enzymatic indicators and thyroid hormones were detected, pathology scores were evaluated, and morphological changes were observed under light microscopy and transmission electron microscopy (TEM) in both groups. The serum levels of triiodothyronine (T3), tetraiodothyronine (T4) and Ca2+ were significantly lower in the SAP group than in the control group (P<0.05), whereas the level of calcitonin (CT) was significantly higher than that in the control group (P<0.05). The thyroid structure (pathology and electron microscopy) of the SAP rats was seriously damaged and worsened over time. SAP can cause thyroid injury through a variety of mechanisms, which can also retroact to pancreatitis to aggravate the inflammatory response. This study may have theoretical significance for basic research on SAP. Key words Severe acute pancreatitis, Thyroid, Structure and functional changes, Transmission electron microscopy.</p>","PeriodicalId":20235,"journal":{"name":"Physiological research","volume":"74 1","pages":"105-114"},"PeriodicalIF":1.9,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11995943/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692923","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":"Direct Effects of Waterpipe Smoke Extract on Aortic Endothelial Cells: An In Vitro Study.","authors":"N E Zaaba, P Yuvarayu, S Beegam, O Elzaki, K Arafat, S Attoub, A Nemmar","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Waterpipe smoking (WPS) has adverse health effects that include endothelial dysfunction with mechanisms involving oxidative stress and inflammation. Nonetheless, there is a scarcity of data on the direct impact of WPS on endothelial function. In this study, we assessed the in vitro effects of waterpipe smoke extract (WPSE) on aortic endothelial cell lines, namely the TeloHAEC. The WPSE markedly caused concentration- and time-dependent decreases in cellular viability. When compared with the control, at a concentration of 20 % and an incubation period of 48 h, the WPSE significantly increased the levels of lactate dehydrogenase, and markers of oxidative stress including thiobarbituric acid reactive substances, superoxide dismutase, catalase, and reduced glutathione. Moreover, the concentrations of proinflammatory cytokine (tumor necrosis factor alpha), and adhesion molecules (E-selectin and intercellular adhesion molecule-1) were also significantly augmented. Likewise, WPSE triggered mitochondrial dysfunction, DNA oxidative damage, as well as apoptosis in TeloHAEC cells. Similarly, cells cultured with WPSE have shown increased expression of phosphorylated nuclear factor-kappaB and hypoxia-inducible factor 1-alpha (HIF-1alpha). In conclusion, our study showed that WPSE triggers endothelial inflammation, oxidative stress, DNA damage, mitochondrial dysfunction, and apoptosis via mechanisms involving the activation of nuclear factor-kappaB and HIF-1alpha. Key words Waterpipe smoking, Aortic endothelial cells, Inflammation, Oxidative Stress.</p>","PeriodicalId":20235,"journal":{"name":"Physiological research","volume":"74 1","pages":"69-78"},"PeriodicalIF":1.9,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11995937/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143691808","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":"Efficacy of Rhythmic Photic Stimulation for Autonomic Nervous System Regulation in University Students.","authors":"S-Y Yang, P-C Wang, C-M Chen, P-H Lin, C Liu","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>University students frequently encounter stress and anxiety, impacting their autonomic nervous system and mental health. Rhythmic photic stimulation (RPS) at various frequencies is considered a potential intervention for anxiety and depression, but its effectiveness is not fully understood. This research aimed to assess the impact of RPS at theta (6 Hz), alpha (10 Hz), and beta (25 Hz) frequencies on autonomic nervous system regulation in university students, comparing the effects between those with and without depression symptoms. Conducted at a southern Taiwan university, this quasi-experimental study involved RPS interventions at specified frequencies, with pre and post assessments of heartbeat, blood pressure, and heart rate variability. Among 62 participants (average age 20.29±0.61), those without depression showed a notable blood pressure reduction following theta-frequency RPS compared to other frequencies (p<0.05). A similar pattern was observed when comparing non-depressed and depressed participants after theta-RPS, with depressed individuals experiencing an increase in sympathetic activity (p<0.05). RPS, particularly at theta frequency, can significantly influence the autonomic nervous system, suggesting a potential for reducing anxiety-related physiological markers in university students. Further verification with a larger and longitudinal study is warranted. Key words Binaural beat, Rhythmical photic stimulation, Autonomic nervous system, University student.</p>","PeriodicalId":20235,"journal":{"name":"Physiological research","volume":"74 1","pages":"149-160"},"PeriodicalIF":1.9,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11995936/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692452","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}