Physiological research最新文献

{"title":"RPS3 Aggravates Sepsis-Induced Acute Kidney Injury Through Activating NF-kappaB Mediated Renal Inflammatory Responses.","authors":"X Zhang, Q Ma, J Wang, Z Zhang, J Zhang","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Excessive inflammatory responses represent one of the primary causes of sepsis- associated acute kidney injury (S-AKI). The activation of the nuclear factor-kappa B (NF-kappaB) signaling pathway plays a critical role in the pathogenesis and progression of S-AKI. Previous studies have demonstrated that ribosomal protein S3 (RPS3) serves as a pivotal regulator of the NF-kappaB pathway; however, its specific biological functions in the context of S-AKI remain to be fully elucidated. This study aims to elucidate the regulatory mechanisms of RPS3 in S-AKI-associated inflammation and to explore the underlying molecular pathways. First, we conducted an analysis of RPS3 level in urine and TNF-alpha level in serum from S-AKI patients recruited at our hospital. Second, we established a murine model of S-AKI by intraperitoneal injection of LPS, followed by the evaluation of renal function, inflammatory response, RPS3 expression, and NF-kappaB activation in renal tissues. Finally, we explored the regulatory role and underlying mechanism of RPS3 in the LPS-induced inflammatory response in HK-2 cells through RPS3 knockdown and the introduction of an NF-kappaB agonist. The results demonstrated that urinary RPS3 and serum TNF-alpha levels were significantly elevated in patients with S-AKI, with a positive correlation observed between these two parameters. In LPS-induced S-AKI mice, renal function was impaired, accompanied by a robust inflammatory response, increased RPS3 protein expression, and enhanced NF-kappaB activation in kidney tissue. Knockdown of RPS3 in HK-2 cells mitigated LPS-induced the inflammatory response and suppressed NF-kappaB activation. However, the effects of RPS3 silencing were partially reversed upon intervention with an NF-kappaB agonist. Collectively, these findings indicate that RPS3 plays a critical role in the inflammatory response of S-AKI via activation of the NF-kappaB signaling pathway, suggesting its potential as a novel therapeutic target for S-AKI. Key words Sepsis-associated acute kidney injury \" Inflammatory response \" Ribosomal protein S3 \" Nuclear factor-kappa B.</p>","PeriodicalId":20235,"journal":{"name":"Physiological research","volume":"75 1","pages":"63-77"},"PeriodicalIF":2.0,"publicationDate":"2026-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13128005/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147434926","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":"Protective Effects of Opuntiol on Lipopolysaccharide-Induced Acute Kidney Injury in Mice.","authors":"Y Li, C Yang, M Liu, C Li, X Li, L Kong","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>This study investigates the protective effect of opuntiol, a naturally occurring flavonoid, against lipopolysaccharide (LPS)-induced acute kidney injury in mice. Acute kidney injury (AKI) is a serious clinical complication characterized by inflammation, oxidative stress, and apoptosis, often resulting in high morbidity and mortality. Male mice were divided into six groups and administered opuntiol (25, 50 and 100 mg/kg b. wt.) intraperitoneally prior to LPS (10 mg/kg b. wt.) administration. The most effective dose was 50 mg/kg b. wt., as indicated in the dose-finding study. Kidney function markers (urea, creatinine, blood urea nitrogen (BUN), uric acid), antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH), inflammatory cytokines tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB), cyclooxygenase-2 (COX-2), and gene expression levels (pro-inflammatory, apoptotic, and antioxidant genes) were analyzed using biochemical assays and qRT-PCR. Opuntiol significantly reduced elevated levels of serum urea, creatinine, BUN, and uric acid compared to the LPS group. Further, opuntiol restored antioxidant enzyme activities and MDA levels were significantly decreased. Opuntiol also downregulated inflammatory markers and gene expressions (TNF-alpha, NF-kappaB, TLR4, Bax, Caspase-3, etc.) while upregulating anti-apoptotic (Bcl-2) and antioxidant (Nrf-2) genes. Opuntiol offers significant protection against LPS-induced AKI by mitigating oxidative damage, inflammation, and apoptotic signaling. It enhances renal function and promotes antioxidant defense. These findings support the therapeutic potential of opuntiol as a novel nephroprotective agent in managing sepsis-associated kidney injury and encourage further preclinical and clinical investigations. Key words Opuntiol \" Acute kidney injury \" Lipopolysaccharide \" Oxidative stress \" Inflammation \" Apoptosis.</p>","PeriodicalId":20235,"journal":{"name":"Physiological research","volume":"75 1","pages":"79-87"},"PeriodicalIF":2.0,"publicationDate":"2026-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13128012/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147434838","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":"Pelargonidin Inhibits Isoproterenol Induced Myocardial Fibrosis via Regulating Transforming Growth Factor-beta/Smad2/3 Signaling and Th2 Cytokines in Mice.","authors":"J Zhao, L Dong, L Yao","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Pelargonidin, a natural anthocyanidin, is known for its anti-inflammatory, antioxidant, and cytoprotective properties, however its role in myocardial fibrosis remains unclear. This study explored the therapeutic potential of pelargonidin in a mouse model of isoproterenol (ISO)-induced myocardial fibrosis. Male C57BL/6 mice were treated with ISO and subsequently administered either a low (20 mg/kg/day) or high (40 mg/kg/day) dose of pelargonidin, with captopril (15 mg/kg/day) serving as a reference control. Histological analysis revealed that pelargonidin significantly reduced collagen deposition in the myocardium in a dose-dependent manner. Molecular assessments showed decreased protein expression of alpha-SMA, COL3A1, and FN1, along with downregulation of TGF-beta/Smad2/3 signaling, as evidenced by reduced levels of TGF-beta and phosphorylated Smad2/3. Additionally, pelargonidin suppressed the expression of extracellular matrix-related genes and decreased circulating levels of Th2 cytokines IL-4 and IL-13. These findings indicate that pelargonidin mitigates myocardial fibrosis by targeting the TGF-beta/Smad2/3 pathway and modulating Th2-mediated immune responses. Overall, the results suggest that pelargonidin may serve as a promising therapeutic agent for myocardial fibrosis and related cardiovascular disorders. Key words Pelargonidin \" Myocardial fibrosis \" Transforming Growth Factor-beta \" Extracellular matrix \" Cytokines.</p>","PeriodicalId":20235,"journal":{"name":"Physiological research","volume":"75 1","pages":"15-27"},"PeriodicalIF":2.0,"publicationDate":"2026-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13127988/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147435066","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 Renal Na+/H+ Exchange in the Regulation of Acid-Base and Sodium Homeostasis in Premature Infants.","authors":"E Sulyok, P Mauchart, B Farkas, Á Várnagy, J Bódis","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Early clinical studies on renal acidifying processes and sodium reabsorption in premature infants were revisited in the context of Na+/H+ exchangers (NHEs) and their developmental regulation. Relevant literature was analyzed to highlight the physiological and clinical significance of NHEs in controlling Na+/H+ exchange during kidney maturation. The immature kidney's low NHE capacity may lead to transient H+ retention, metabolic acidosis, sodium depletion, and late hyponatremia in premature infants. Sodium depletion excessively activates the renin-angiotensin-aldosterone system (RAAS), which stimulates NHE, reduces sodium loss, and mitigates late metabolic acidosis. Interestingly, NaCl supplementation suppresses systemic RAS activity while also preventing late metabolic acidosis, potentially through renal RAS-mediated NHE upregulation. Circulating and renal RAS may have distinct roles in regulating NHE activation and in maturity-related changes in sodium and acid-base homeostasis in premature infants. Key words Renal immaturity \" Na+/H+ exchange \" Hormonal regulation.</p>","PeriodicalId":20235,"journal":{"name":"Physiological research","volume":"75 1","pages":"3-13"},"PeriodicalIF":2.0,"publicationDate":"2026-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13127995/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147434900","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":"Platelet Count and Platelet Indices as Predictive Markers of COVID-19 Mortality.","authors":"Z Kozelová, D Jarčušková, L Tomčo, L Lacková, Z Kozárová, M Valiková Bavoľárová, L Rušinová, M Kozárová","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The aim of the study was to analyze changes in platelet count and function in hospitalized COVID-19 patients and compare them with non-COVID-19 patients, focusing on the association between platelet indices and mortality beyond the known link between neutrophil-to-lymphocyte ratio (NLR) and COVID-19 severity. The study sample consisted of 572 patients, out of which 472 were hospitalized with COVID-19 infection from 15th October 2021 to 30th April 2022 in Louis Pasteur University Hospital Kosice, Slovak Republic and 100 represented the control group without COVID-19 infection. COVID-19 positive patients (n=472) had significantly larger size of platelets (MPV 9.2+/-1.4 vs. 8.8+/-1.2, p=0.002) and therefore a higher percentage of platelets larger than 12 fl (P-LCR 33.7 % vs. 24.8 %, p=0.002) than patients in the control group (non-COVID19). The statistically significant relationship was between mortality in patients with COVID-19 infection (n=122) and the larger size of the platelets (MPV), higher platelet large cell ratio, (P-LCR), higher PLT/MPV ratio, higher platelet distribution width to plateletcrit ratio (PDW/PCT), higher neutrophil-to-lymphocyte ratio (NLR) (p<0.001, respectively) and lower platelet count (PLT) and lower plateletcrit (PCT) (p=0.006; p=0.028; respectively). In multivariable logistic regression analysis, a significant positive correlation between mortality, MPV (OR 2.29; 95 % CI 1.70-3.08, p<0.001) and age (OR 1.06; 1.03-1.08, p<0.001) was observed. When NLR was included into this model, MPV was stronger predictor of mortality (OR 2.48; 95 % CI 1.79-3.43, p<0.001) compared to NLR (OR 1.06; 95 % CI 1.03-1.08, p<0.001) and age (OR 1.04; 95 % CI 1.02-1.07, p<0.001). MPV is a strong and independent predictor of mortality in hospitalized COVID-19 patients, demonstrating superior prognostic value compared to established association between neutrophil-to-lymphocyte ratio (NLR) and COVID-19 severity. As a simple and routinely available parameter from standard blood count, MPV may serve as a practical and accessible tool for early risk stratification in the clinical management of COVID-19. Key words Platelets \" COVID-19 \" Mean platelet volume \" Neutrophil to lymphocyte ratio \" Mortality.</p>","PeriodicalId":20235,"journal":{"name":"Physiological research","volume":"75 1","pages":"55-61"},"PeriodicalIF":2.0,"publicationDate":"2026-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13128002/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147434097","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":"Role of PKM2 Tetramer in Modulating Endothelial Mitochondrial Dysfunction in a Rat Model of Chronic Thromboembolic Pulmonary Hypertension.","authors":"M-X Yang, Z-Z Wu, D-W Wu, M-H Chen, Q-X Wu, N Shao, C-S Deng","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Dysfunction of pulmonary artery endothelial cells (PAECs) contributes to the pathogenesis of chronic thromboembolic pulmonary hypertension (CTEPH). However, the role of mitochondrial metabolism in this process remains unclear. The present study evaluated whether the tetrameric form of pyruvate kinase muscle isoform 2 (PKM2) regulates PAEC mitochondrial metabolism through peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1alpha) and mitochondrial transcription factor A (mtTFA), thereby influencing arterial intimal remodeling in CTEPH. A CTEPH rat model was established by repeated injections of autologous thrombi. Activation of PKM2 tetramer expression was achieved through synthetic pyruvate kinase M2 activator (TEPP-46) administration. Pulmonary artery pressure (PAP), thrombus pathology, and protein expression levels of PKM2, mtTFA, and PGC-1alpha were assessed. Plasma lactate concentrations and tumor necrosis factor alpha (TNF-alpha) levels were measured. Rats with CTEPH demonstrated thrombotic obstruction, elevated PAP, and reduced expression of the PKM2 tetramer, mtTFA, and PGC-1alpha. Treatment with TEPP-46 was associated with a reduction in thrombus burden, lower PAP, and restoration of mitochondrial protein expression, accompanied by decreased lactate concentrations and TNF-alpha levels. In the CTEPH rat model, increased inflammation and elevated lactate concentrations were observed, along with decreased expression of mtTFA and PGC-1alpha in the pulmonary artery intima, which is indicative of mitochondrial dysfunction. The PKM2 tetramer may play a role in modulating PAEC mitochondrial function, reducing pulmonary artery pressure, and improving pulmonary arterial intimal remodeling in CTEPH. Key words Chronic thromboembolic pulmonary hypertension \" Lactic acid \" Mitochondrial transcription factor A \" Peroxisome proliferator-activated receptor gamma coactivator 1alpha \" Pyruvate kinase muscle.</p>","PeriodicalId":20235,"journal":{"name":"Physiological research","volume":"75 1","pages":"45-53"},"PeriodicalIF":2.0,"publicationDate":"2026-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13128003/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147434860","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":"Glucagon-Like Peptide-2 Ameliorates Lipid Metabolism in Metabolic Dysfunction-Associated Steatotic Liver Disease Through the Adiponectin-Adiponectin Receptor-Mediated AMPK/PPARalpha Pathway.","authors":"S-J Zhang, K Xu, F Zhu, J-G Chen, Y Zhang, Y-Q Teng, F-F Shen","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The aim of this study was to investigate the mechanisms by which glucagon-like peptide-2 (GLP-2) improves metabolic dysfunction-associated steatotic liver disease (MASLD) induced by free fatty acids (FFAs) in HepG2 cells, with a focus on the regulation of the adiponectin (ADPN) signaling axis and the downstream AMP-activated protein kinase (AMPK)/peroxisome proliferator-activated receptor alpha (PPARalpha) pathway. An MASLD model was established in HepG2 cells by FFA exposure. Following GLP-2 treatment, improvements in lipid metabolism were evaluated using the Cell Counting Kit-8, Oil Red O staining, and biochemical assays. Differential gene expression was examined using RNA sequencing, and potential mechanisms were evaluated through Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analysis. Western blotting and reverse transcription polymerase chain reaction (RT-PCR) were performed to assess the expression of key molecular components within the signaling pathway. FFA treatment led to significant lipid accumulation in HepG2 cells, whereas GLP-2 reduced intracellular lipid droplet formation (p<0.01) and decreased triglyceride and total cholesterol levels in a dose-dependent manner (p<0.05). KEGG enrichment analysis indicated that GLP-2 acted on the adipokine, AMPK, and PPARalpha pathways. Western blotting and RT-PCR confirmed that GLP-2 restored protein expression (p<0.01) and mRNA expression (p<0.05) of adiponectin receptor 1, adiponectin receptor 2, and downstream signaling molecules AMPK and PPARalpha in FFA-treated HepG2 cells. GLP-2 alleviated FFA-induced hepatocyte steatosis by modulating the AMPK/PPARalpha pathway through the regulation of ADPN and its receptors. These findings provide a theoretical foundation for the potential use of gut hormones in the treatment of MASLD. Keywords Adiponectin \" AMPK \" Glucagon-like peptide-2 \" Metabolic dysfunction-associated steatotic liver disease \" PPARalpha.</p>","PeriodicalId":20235,"journal":{"name":"Physiological research","volume":"75 1","pages":"113-126"},"PeriodicalIF":2.0,"publicationDate":"2026-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13127996/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147435041","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":"TMAO Induced Kidney Aging by Activating ZBP1-Mediated Necroptosis.","authors":"Q Chen, Z Qiu, Y Zhao, L Bai, Y Chan, S Jin, F Ma, J Dai","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The present study was aimed to investigate whether trimethylamine-N-oxide (TMAO) contributed to kidney aging by activating necroptosis. Male C57BL/6J mice were randomly divided into Control group (3 months old) and Old group (18 months old), compared to 3-month-old controls, 18-month-old male C57BL/6J mice showed significant increases in plasma creatinine (Cre) and blood urea nitrogen (BUN) (P<0.05), enhanced renal fibrosis (P<0.001), elevated plasma TMAO (P<0.01), and upregulation of senescence markers p53, p21, and p16 (P<0.05, P<0.01, and P<0.001, respectively). In order to investigate the effects of TMAO on kidney aging, the mice were intraperitoneally injected with TMAO for one to three months, mice showed time-dependent increases in Cre and BUN (P<0.05, respectively), progressive fibrosis, and gradual upregulation of senescence markers, ZBP1, and phosphorylation of RIPK3 and MLKL (P<0.05, respectively). In addition, three months of DMB treatment (inhibitor for TMAO formation) significantly reduced the plasma Cre and BUN levels (P<0.001 and P<0.05), downregulated the senescence markers expression, and improved kidney fibrosis (P<0.001 or P<0.05, respectively). In conclusion, our studies revealed that TMAO induced kidney aging by activating ZBP1-mediated necroptosis. Moreover, the inhibition of TMAO generation might be a potential treatment for kidney aging. Key words Kidney aging \" Trimethylamine-N-oxide \" ZBP1 \" Necroptosis \" DMB.</p>","PeriodicalId":20235,"journal":{"name":"Physiological research","volume":"75 1","pages":"89-98"},"PeriodicalIF":2.0,"publicationDate":"2026-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13127997/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147434879","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":"Targeting the Toll-Like Receptor 4 Ameliorates Heart Failure in Aged Mice by Inhibiting the Formation of Neutrophil Extracellular Traps.","authors":"H Liu, X Chen, Z Wu","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Heart failure (HF) is a prevalent cardiovascular condition among the elderly population, with an incidence rate that continues to rise annually, highlighting the urgent need for effective therapeutic interventions. Sustained activation of Toll-like receptor 4 (TLR4) may contribute to left ventricular dysfunction and adverse cardiac remodeling through the induction of myocardial inflammation and oxidative stress - pathological processes that closely align with the hallmark features of HF. Preclinical studies in animal models have demonstrated that TLR4 deficiency improves cardiac function in aged mice; however, the precise role and underlying mechanisms of TLR4 in human HF remain poorly understood. This study aims to test the central hypothesis that TLR4 serves as a critical molecular link between chronic inflammation and the pathophysiology of HF. HF was induced in 18-month-old male C57BL/6J mice via continuous subcutaneous infusion of isoproterenol (ISO, 30 mg/kg/day) over a period of 3 weeks. Thereafter, mice received daily intraperitoneal injections of the TLR4 inhibitor TAK-242 (2 mg/kg), deoxyribonuclease I (DNase I, 5 mg/kg), or the peptidylarginine deiminase 4 (PAD4) inhibitor GSK484 (4 mg/kg) for 7 consecutive days. Cardiac function was assessed using a ultrasound imaging system. HE staining and Masson staining were employed to evaluate myocardial pathological changes and collagen deposition. ELISA was performed to measure serum levels of myeloperoxidase-DNA (MPO-DNA), neutrophil elastase-DNA (NE-DNA), cTnI, NT-proBNP, IL-1beta, IL-6 and TNF-alpha. Immunofluorescence staining was performed to detect the co-localization levels of Ly6G with myeloperoxidase (MPO) and citrullinated histone H3 (cit-H3) in myocardial tissue, in order to assess the formation level of neutrophil extracellular traps (NETs). Western blot were utilized to determine the expression level of TLR4 protein. The expression of TLR4 was significantly upregulated in the myocardial tissue of aged HF mice. Inhibition of TLR4 not only markedly improved cardiac function but also alleviated pathological damage to myocardial tissue and reduced collagen fiber deposition. Concurrently, it also decreased the serum levels of MPO-DNA, NE-DNA, NT-proBNP, cTnI, and inflammatory factors. Moreover, the colocalization levels of Ly6G with MPO or cit-H3 in myocardial tissue was also diminished. These findings were consistent with the effects observed following DNase I and GSK484 interventions. Targeting TLR4 can mitigate inflammatory responses and enhance cardiac function in HF mice by inhibiting NETs formation. Key words Heart failure \" Cardiac function \" Inflammation \" Toll-like receptor 4 \" Neutrophil extracellular traps.</p>","PeriodicalId":20235,"journal":{"name":"Physiological research","volume":"75 1","pages":"29-43"},"PeriodicalIF":2.0,"publicationDate":"2026-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13128013/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147434876","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":"Reactivity of Isolated Arteries After 5-Week-Lasting Period of Intermittent Fasting Followed by the Return to Ad Libitum Regimen in Healthy Rats Fed With Normal and High-Fat Diet.","authors":"A Zemančíková, J Török, M Kvandová, M Olos, P Bališ","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Intermittent fasting (IF) represents one of the dietary regimens being effectively used in non-pharmacological prevention and treatment of cardiometabolic disorders. The aim of the present study was to detect the retained alterations at the level of arterial function caused by a 5-week-lasting period of IF in adult male Wistar-Kyoto rats after their switching back to ordinary feeding (4 weeks of ad libitum regimen). The rats were administered a diet containing normal or high percentage of fat. Control rat groups were fed continuously ad libitum. The decreased weekly calorie intake in rats during IF period was associated with the discontinuation of body weight gain, irrespective of the type of diet; moreover, rats fed with a high-fat diet had significantly increased systolic blood pressure in comparison with the other groups. At the end of the experiment, large and small arteries were isolated from the rats and arterial rings with intact or removed perivascular adipose tissue (PVAT) were prepared for isometric tension recording. In the rat groups exposed to IF period, the aorta rings with intact PVAT showed a significant increase in relaxation responses when compared to groups without IF. The effect of IF was also manifested in the increase in sensitivity of arterial preparations to noradrenaline which was, however, mostly attenuated by the enhanced anticontractile influence of PVAT. These results indicate that the improvement of PVAT properties could represent one of the mechanisms by which IF-induced beneficial effects on vascular function might be preserved even after the return to ad libitum regimen.</p>","PeriodicalId":20235,"journal":{"name":"Physiological research","volume":"74 Suppl 2","pages":"S219-S229"},"PeriodicalIF":2.0,"publicationDate":"2025-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12849786/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145966532","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}