Frontiers in PhysiologyPub Date : 2025-01-31eCollection Date: 2025-01-01DOI: 10.3389/fphys.2025.1525836
Francisco J Chorro, Luis Such-Miquel, Samuel Cuñat, Oscar Arias-Mutis, Patricia Genovés, Manuel Zarzoso, Antonio Alberola, Luis Such-Belenguer, Irene Del Canto
{"title":"Effects of Eleclazine (GS6615) on the proarrhythmic electrophysiological changes induced by myocardial stretch.","authors":"Francisco J Chorro, Luis Such-Miquel, Samuel Cuñat, Oscar Arias-Mutis, Patricia Genovés, Manuel Zarzoso, Antonio Alberola, Luis Such-Belenguer, Irene Del Canto","doi":"10.3389/fphys.2025.1525836","DOIUrl":"https://doi.org/10.3389/fphys.2025.1525836","url":null,"abstract":"<p><strong>Purpose: </strong>Myocardial stretch is a proarrhythmic factor. Eleclazine (GS6615) is a late sodium current (INaL) inhibitor that has shown protective effects against arrhythmias in various experimental models. Data on its effects during myocardial stretch are lacking. The aim of this study was to investigate the electrophysiological modifications induced by eleclazine basally and during acute ventricular stretch.</p><p><strong>Methods: </strong>Left ventricular stretch was induced at baseline and during perfusion with eleclazine in 26 Langendorff rabbit heart preparations. Programmed stimulation and high-resolution mapping techniques were applied using multiple epicardial electrodes.</p><p><strong>Results: </strong>At baseline, both the ventricular refractory period measured at a fixed cycle length (250 m) and its surrogate obtained during ventricular fibrillation (VF) decreased significantly during stretch (baseline 128 ± 15 vs. stretch 110 ± 14 m; n = 15; p < 0.001, and baseline 52 ± 13 vs. stretch 44 ± 9 m; n = 11; p < 0.05), while the VF dominant frequency (DF) increased significantly (DF baseline 13 ± 3 vs. stretch 17 ± 5Hz; n = 11; p < 0.01). Eleclazine 1.4 μM prolonged refractoriness, diminished both DF and conduction velocity during the arrhythmia, and avoided the stretch induced variations in refractoriness (baseline 148 ± 19 vs. stretch 150 ± 23 m; n = 15; ns, and baseline 73 ± 15 vs. stretch 77 ± 15 m; n = 11; ns) and in DF (baseline 12 ± 5 vs. stretch 12 ± 3 Hz; ns). The VF complexity index was inversely related to refractoriness (r = -0.64; p < 0.001). Under eleclazine perfusion, the VF activation patterns were less complex, and the arrhythmia stopped in 6 out of 11 experiments (55%; p < 0.05 vs. baseline).</p><p><strong>Conclusion: </strong>Eleclazine (GS6615) reduced the proarrhythmic electrophysiological changes induced by myocardial stretch and slowed and simplified activation patterns during VF in the experimental model used.</p>","PeriodicalId":12477,"journal":{"name":"Frontiers in Physiology","volume":"16 ","pages":"1525836"},"PeriodicalIF":3.2,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11825515/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143432857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Frontiers in PhysiologyPub Date : 2025-01-31eCollection Date: 2025-01-01DOI: 10.3389/fphys.2025.1541198
Ze-Hou Wang, Zong-Jin Zhang, Yue-Fen Wang, Jin Xie, Yi-Min Li, Cun Shen, Yuan Meng, Wen-Jing Zhao, Lu-Ying Sun, Wei Jing Liu
{"title":"Serum advanced glycation end products as a putative biomarker in Type2 DKD patients' prognosis.","authors":"Ze-Hou Wang, Zong-Jin Zhang, Yue-Fen Wang, Jin Xie, Yi-Min Li, Cun Shen, Yuan Meng, Wen-Jing Zhao, Lu-Ying Sun, Wei Jing Liu","doi":"10.3389/fphys.2025.1541198","DOIUrl":"https://doi.org/10.3389/fphys.2025.1541198","url":null,"abstract":"<p><strong>Aim: </strong>Advanced glycation end products (AGEs) are pivotal mediators in diabetic kidney disease (DKD). However, their prognostic utility remains underexplored. This study introduced corrected lgAGEs [novel biomarker derived by adjusting logarithmically transformed AGEs (lgAGEs) levels based on serum albumin (ALB) levels] to enhance the prediction of adverse renal outcomes in patients with type 2 DKD (T2DKD).</p><p><strong>Methods: </strong>In this prospective cohort study, 196 T2DKD patients were followed up longitudinally. Serum AGEs levels were log-transformed and adjusted for ALB to calculate corrected lgAGEs. Participants were stratified into the high- and low-level groups based on the median corrected lgAGEs. The association between corrected lgAGEs and renal outcomes was assessed using Cox proportional hazards models. Receiver operating characteristic (ROC) curve was utilized to evaluate the predictive performance of corrected lgAGEs alone and in combination with the urinary albumin-to-creatinine ratio (UACR).</p><p><strong>Results: </strong>High level of corrected lgAGEs was independently associated with adverse renal outcomes [hazard ratio (HR), 3.252; 95% confidence interval (CI), 1.461-7.243; <i>p</i> = 0.003]. Kaplan-Meier analysis demonstrated that patients in the high-level group (12 months) exhibited significantly shorter median survival times compared with those in the low-level group (50 months). ROC analysis showed that UACR alone had an area under the curve (AUC) of 0.782 (95% CI, 0.705-0.858), with 82.8% sensitivity and 61.5% specificity. Corrected lgAGEs achieved an AUC of 0.725 (95% CI, 0.637-0.814), with 69.0% sensitivity and 76.9% specificity. Combining UACR and corrected lgAGEs improved the specificity to 75.6%, with an AUC of 0.764 (95% CI, 0.682-0.847), while maintaining a sensitivity of 70.7%.</p><p><strong>Conclusion: </strong>Corrected lgAGEs are novel and independent biomarkers for predicting adverse renal outcomes in T2DKD. Combining UACR with corrected lgAGEs could enhance risk stratification by improving the specificity, highlighting its potential application in early identification of high-risk patients. These findings should be validated in broader populations in future research.</p>","PeriodicalId":12477,"journal":{"name":"Frontiers in Physiology","volume":"16 ","pages":"1541198"},"PeriodicalIF":3.2,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11825471/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143432861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Frontiers in PhysiologyPub Date : 2025-01-30eCollection Date: 2025-01-01DOI: 10.3389/fphys.2025.1475391
Wantang Su, Jianming Liu, Aozhe Wang, Haifeng Zhang, Yaqi Sun, Zhiyi Yan, Michael Svensson, Ji-Guo Yu, Li Zhao
{"title":"Distinct lipidomic profiles but similar improvements in aerobic capacity following sprint interval training versus moderate-intensity continuous training in male adolescents.","authors":"Wantang Su, Jianming Liu, Aozhe Wang, Haifeng Zhang, Yaqi Sun, Zhiyi Yan, Michael Svensson, Ji-Guo Yu, Li Zhao","doi":"10.3389/fphys.2025.1475391","DOIUrl":"10.3389/fphys.2025.1475391","url":null,"abstract":"<p><strong>Background: </strong>Exercise-induced metabolic changes, especially lipidomic changes are generally associated with improvements in cardiovascular health. Despite numerous previous studies, the differences in lipidomic profile response to different types of exercise training remain unclear. This study aimed to investigate how two different exercise intensities affect aerobic capacity and serum lipidomic profiles in healthy adolescents.</p><p><strong>Methods: </strong>Twenty-four healthy untrained male adolescents (13.08 ± 0.88 years old) were recruited and randomly assigned to moderate-intensity continuous training (MICT) group or sprint interval training (SIT) group to complete a specific training on a cycle ergometer for 6 weeks. Peak oxygen uptake (VO<sub>2</sub>peak) and body composition were measured, and blood samples were collected for serum lipoproteins and lipidomic analysis. Anthropometric, VO<sub>2</sub>peak, and serum biochemical data were analyzed using two-way repeated analysis of variance, while targeted lipidomic analysis was performed by principal component analysis and paired-sample <i>t</i>-test.</p><p><strong>Results: </strong>VO<sub>2</sub>peak significantly improved from 39.05 ± 8.17 to 47.52 ± 8.51 [F (1, 44) = 14.75, <i>p</i> < 0.05] for MICT and from 40.13 ± 6.37 to 48.42 ± 7.01 [F (1, 44) = 14.75, <i>p</i> < 0.05] for SIT. A total of 28 lipids in MICT and 5 lipids in SIT showed significant changes out of 276 identified lipids (FC > 1.5 or <1/1.5, FDR <0.05). In MICT, 21 lipids, including sphingolipid (SP) and phospholipid (PL), decreased, while 7 lipids increased. In SIT, all 5 lipids, which were free fatty acid (FFA), decreased.</p><p><strong>Conclusion: </strong>Although both MICT and SIT induced similar and significant improvements in VO<sub>2</sub>peak, serum lipid adaptations to the training differed. The primary changes in serum lipidomic intermediates for both types of training were reductions; however, SIT affected FFA, while MICT predominantly influenced SPs and PLs.</p>","PeriodicalId":12477,"journal":{"name":"Frontiers in Physiology","volume":"16 ","pages":"1475391"},"PeriodicalIF":3.2,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11821953/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143413826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Frontiers in PhysiologyPub Date : 2025-01-30eCollection Date: 2025-01-01DOI: 10.3389/fphys.2025.1537537
Yueying Shi, Xiaoxiao Bai, Jingrong Yang, Xinyu Wu, Lei Wang
{"title":"Optimized measurement methods and systems for the dielectric properties of active biological tissues in the 10Hz-100 MHz frequency range.","authors":"Yueying Shi, Xiaoxiao Bai, Jingrong Yang, Xinyu Wu, Lei Wang","doi":"10.3389/fphys.2025.1537537","DOIUrl":"10.3389/fphys.2025.1537537","url":null,"abstract":"<p><p>The dielectric properties of active biological tissues within the 10Hz-100 MHz frequency range contain rich information about tissue morphology and function. Accurately understanding the dielectric properties of active human tissues holds significant value for disease diagnosis and electromagnetic protection. However, accurately measuring these properties has been challenging due to factors such as electrode polarization and distribution parameters. This study has developed a dual-purpose measuring cell that supports both four-electrode and two-electrode impedance measurements. Leveraging this development, we have established a system and methodology that is well-suited for the dielectric property measurement of active biological tissues within the frequency range of 10Hz to 100 MHz. Our measurements of dielectric properties in NaCl solutions of varying concentrations and pig liver tissues demonstrate the system's high accuracy and repeatability. For NaCl solutions, the maximum relative deviation is only 6.34%, with an average deviation of less than 1.5%. For pig liver tissues, the overall relative deviation is below 6%. Through the integration of the four-electrode and two-electrode measurement systems, we have successfully addressed the challenges of electrode polarization at low frequencies and the influence of distribution parameters at high frequencies, achieving a significant improvement in measurement accuracy across the spectrum.</p>","PeriodicalId":12477,"journal":{"name":"Frontiers in Physiology","volume":"16 ","pages":"1537537"},"PeriodicalIF":3.2,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11821640/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143413818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Frontiers in PhysiologyPub Date : 2025-01-30eCollection Date: 2025-01-01DOI: 10.3389/fphys.2025.1430946
Mira Hanna, Ahmed M A Akabawy, Mohamed Mansour Khalifa, Marawan Abd Elbaset, Reda Abdelnasser Imam, Hanan Seddiek
{"title":"Intracellular iron accumulation throughout the progression of sepsis influences the phenotype and function of activated macrophages in renal tissue damage.","authors":"Mira Hanna, Ahmed M A Akabawy, Mohamed Mansour Khalifa, Marawan Abd Elbaset, Reda Abdelnasser Imam, Hanan Seddiek","doi":"10.3389/fphys.2025.1430946","DOIUrl":"10.3389/fphys.2025.1430946","url":null,"abstract":"<p><p>Sepsis, the most common cause of acute kidney injury, remains a major socioeconomic burden. A dysregulated immune response leads to progressive organ dysfunction. Although numerous inflammatory pathways were described, most are still vague and need to be studied in terms of the mechanisms to improve the therapeutic intervention. We tackled the relationship between intracellular iron overload and macrophage polarization within 6, 24, and 72 h of sepsis induction. In our study, sepsis-induced kidney injury was caused by using the cecal ligation and puncture (CLP) model. Our results indicated severe renal tissue damage with a progressive increase in serum BUN and creatinine with architectural tissue damage and positive PAS staining. There was increased expression of CD8<sup>+</sup> CD68<sup>+</sup> M1 macrophage markers with upregulation of iNOS and co-expression of CD163<sup>+</sup>. Alternatively, Arg1<sup>+</sup> Fizz1<sup>+</sup> M2 macrophage markers were downregulated with increased iNOS/Arg1 ratio. TFR1, cubilin, and DMT1, as iron transport systems, were increased compared to sham but were significant after 72 h, while ZIP8 showed no significant change. There was a correlation between iron overload and M1 macrophage polarization with CD163<sup>+</sup> phenotype, together with fibrotic changes. The intracellular iron overload with downregulation of ferritin was strongly related to macrophage polarization that was exaggerated at 72 h. Finally, early introduced therapy to target free iron during sepsis is a proposed novel solution for protecting the renal tissue from acute injury due to macrophage activation that may end up with chronic kidney injury, if not mortality.</p>","PeriodicalId":12477,"journal":{"name":"Frontiers in Physiology","volume":"16 ","pages":"1430946"},"PeriodicalIF":3.2,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11821637/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143413831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Frontiers in PhysiologyPub Date : 2025-01-30eCollection Date: 2024-01-01DOI: 10.3389/fphys.2024.1527523
Georg Langen, Frank Warschun, Olaf Ueberschär, Michael Behringer
{"title":"The interaction of post-activation potentiation and fatigue on skeletal muscle twitch torque and displacement.","authors":"Georg Langen, Frank Warschun, Olaf Ueberschär, Michael Behringer","doi":"10.3389/fphys.2024.1527523","DOIUrl":"10.3389/fphys.2024.1527523","url":null,"abstract":"<p><strong>Introduction: </strong>Tensiomyography (TMG) assesses skeletal muscle contractile properties based on the electrically stimulated radial muscle displacement. As the relationship between twitch displacement and associated torque is poorly understood, it is unclear how it is affected by post-activation potentiation and muscle fatigue. This study investigated how the interaction of potentiation and fatigue affects the rectus femoris (RF) twitch displacement and associated torque.</p><p><strong>Materials and methods: </strong>Sixteen resistance-trained men (n = 8) and women (n = 8) performed two sets of five and five sets of ten seated maximum voluntary isometric knee extensions to induce potentiation and fatigue. Twitch displacement and torque were measured at baseline before the first set, after each set, and every 2 min for 15 min after the last set.</p><p><strong>Results: </strong>The exercise effectively induced potentiation and fatigue as peak twitch torque increased by 44.1% after the first set, decreased by 32.9% after the last set and remained decreased by 26.4% after 15 min. Twitch displacement was considerably less affected by the exercise. Consequently, TMG parameters could not accurately detect potentiated or fatigued participants as indicated by the peak twitch torque.</p><p><strong>Discussion: </strong>The TMG parameters' insufficient diagnostic accuracy likely resulted from a reduced signal-to-noise ratio at 90° knee flexion and the associated longer muscle length of the RF, compared to more extended knee angles commonly employed in TMG studies. These results highlight an important methodological consideration as the joint angle, i.e. muscle length, appears to influence the TMG parameters' ability to detect exercise-induced changes in contractile properties.</p>","PeriodicalId":12477,"journal":{"name":"Frontiers in Physiology","volume":"15 ","pages":"1527523"},"PeriodicalIF":3.2,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11821631/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143413815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Frontiers in PhysiologyPub Date : 2025-01-29eCollection Date: 2024-01-01DOI: 10.3389/fphys.2024.1477070
Ruoting Yang, Aarti Gautam, Rasha Hammamieh, Robert C Roach, Beth A Beidleman
{"title":"Transcriptomic signatures of severe acute mountain sickness during rapid ascent to 4,300 m.","authors":"Ruoting Yang, Aarti Gautam, Rasha Hammamieh, Robert C Roach, Beth A Beidleman","doi":"10.3389/fphys.2024.1477070","DOIUrl":"10.3389/fphys.2024.1477070","url":null,"abstract":"<p><strong>Introduction: </strong>Acute mountain sickness (AMS) is a common altitude illness that occurs when individuals rapidly ascend to altitudes ≥2,500 m without proper acclimatization. Genetic and genomic factors can contribute to the development of AMS or predispose individuals to susceptibility. This study aimed to investigate differential gene regulation and biological pathways to diagnose AMS from high-altitude (HA; 4,300 m) blood samples and predict AMS-susceptible (AMS+) and AMS-resistant (AMS─) individuals from sea-level (SL; 50 m) blood samples.</p><p><strong>Methods: </strong>Two independent cohorts were used to ensure the robustness of the findings. Blood samples were collected from participants at SL and HA. RNA sequencing was employed to profile gene expression. Differential expression analysis and pathway enrichment were performed to uncover transcriptomic signatures associated with AMS. Biomarker panels were developed for diagnostic and predictive purposes.</p><p><strong>Results: </strong>At HA, hemoglobin-related genes (HBA1, HBA2, and HBB) and phosphodiesterase 5A (PDE5A) emerged as key differentiators between AMS+ and AMS- individuals. The cAMP response element-binding protein (CREB) pathway exhibited contrasting regulatory patterns at SL and HA, reflecting potential adaptation mechanisms to hypoxic conditions. Diagnostic and predictive biomarker panels were proposed based on the identified transcriptomic signatures, demonstrating strong potential for distinguishing AMS+ from AMS- individuals.</p><p><strong>Discussion: </strong>The findings highlight the importance of hemoglobin-related genes and the CREB pathway in AMS susceptibility and adaptation to hypoxia. The differential regulation of these pathways provides novel insights into the biological mechanisms underlying AMS. The proposed biomarker panels offer promising avenues for the early diagnosis and prediction of AMS risk, which could enhance preventive and therapeutic strategies.</p>","PeriodicalId":12477,"journal":{"name":"Frontiers in Physiology","volume":"15 ","pages":"1477070"},"PeriodicalIF":3.2,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11813865/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143406746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Frontiers in PhysiologyPub Date : 2025-01-29eCollection Date: 2024-01-01DOI: 10.3389/fphys.2024.1497297
James P Hardwick, Byoung-Joon Song, Paul Rote, Charles Leahy, Yoon Kwang Lee, Alexandra Rudi Wolf, Danielle Diegisser, Victor Garcia
{"title":"The CYP4/20-HETE/GPR75 axis in the progression metabolic dysfunction-associated steatosis liver disease (MASLD) to chronic liver disease.","authors":"James P Hardwick, Byoung-Joon Song, Paul Rote, Charles Leahy, Yoon Kwang Lee, Alexandra Rudi Wolf, Danielle Diegisser, Victor Garcia","doi":"10.3389/fphys.2024.1497297","DOIUrl":"https://doi.org/10.3389/fphys.2024.1497297","url":null,"abstract":"<p><strong>Introduction: </strong>Metabolic-dysfunction-associated steatosis liver disease (MASLD) is a progressive liver disease from simple steatosis, steatohepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. Chronic liver diseases (CLDs) can lead to portal hypertension, which is a major cause of complications of cirrhosis. CLDs cause structural alterations across the liver through increased contents of extracellular matrix (ECM), driving dysfunction of liver sinusoidal endothelial cells (LSECs) alongside hepatic stellate cells (HSCs) and activated resident or infiltrating immune cells. Bioactive arachidonic metabolites have diverse roles in the progression of MASLD. Both secreted levels of 20-hydroxyeicosatetraenoic acid (20-HETE) and epoxyeicosatrienoic acid (EET) are elevated in patients with liver cirrhosis.</p><p><strong>Methods: </strong>CLD samples were evaluated for changes in free fatty acids (FFA), cholesterol, bilirubin, bile acid, reactive oxygen species (ROD), lipid peroxidation, myeloperoxidase activity and hydroxyproline levels to evaluate the degrees of liver damage and fibrosis. To address the role of the CYP4/20-HETE/GPR75 axis, we measured the amount and the synthesis of 20-HETE in patients with CLD, specifically during the progression of MASLD. Additionally, we evaluated gene expression and protein levels of GPR75, a high-affinity receptor for 20-HETE across CLD patient samples.</p><p><strong>Results: </strong>We observed an increase in 20-HETE levels and synthesis during the progression of MASLD. Increased synthesis of 20-HETE correlated with the expression of <i>CYP4A11</i> genes but not CYP4F2. These results were confirmed by increased P4504A11 protein levels and decreased P4504F2 protein levels during the development and progression of MASLD. The gene expression and protein levels of GPR75, the major receptor for 20-HETE, increased in the progression of MASLD. Interestingly, the <i>CYP4A11</i> and <i>GPR75</i> mRNA levels increased in steatohepatitis but dramatically dropped in cirrhosis and then increased in patients with HCC. Also, protein levels of P4504A11 and GPR75 mirrored their mRNA levels.</p><p><strong>Discussion: </strong>These results indicate that the <i>CYP4A11</i> and subsequent <i>GPR75</i> genes are coordinately regulated in the progression of MASLD and may have multiple roles, including 20-HETE activation of peroxisome proliferator-activated receptor α (PPARα) in steatosis and GPR75 in CLD through either increased cell proliferation or vasoconstriction in portal hypertension during cirrhosis. The abrupt reduction in <i>CYP4A11</i> and <i>GPR75</i> in patients with cirrhosis may also be due to increased 20-HETE, serving as a feedback mechanism via <i>GPR75</i>, leading to reduced <i>CYP4A11</i> and <i>GPR75</i> gene expression. This work illustrates key correlations associated with the CYP4/20-HETE/GPR75 axis and the progression of liver disease in humans.</p>","PeriodicalId":12477,"journal":{"name":"Frontiers in Physiology","volume":"15 ","pages":"1497297"},"PeriodicalIF":3.2,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11826315/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143432751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Frontiers in PhysiologyPub Date : 2025-01-28eCollection Date: 2024-01-01DOI: 10.3389/fphys.2024.1511960
Jessica M L Grittner, Rebecca Barok, Edgar Juarez Lopez, Misha Shah, Brendan J Dougherty
{"title":"Age and estrogen-associated reductions in hypoxic ventilatory response and chemosensitivity in female rats.","authors":"Jessica M L Grittner, Rebecca Barok, Edgar Juarez Lopez, Misha Shah, Brendan J Dougherty","doi":"10.3389/fphys.2024.1511960","DOIUrl":"10.3389/fphys.2024.1511960","url":null,"abstract":"<p><p>Respiratory function is modulated by circulating steroid hormones. In female rats, steroid hormones fluctuate across the normal estrous cycle and decline with age, similar to human menopause. To determine the influence of steroid hormones, and mimic aspects of age-related reductions in hormones, the ovariectomy model is often employed. Ovariectomy (OVX) induces an immediate and persistent decrease in steroid hormones. The current study aimed to interrogate whether the OVX model of hormone reduction impacted specific aspects of respiratory function [chemosensitivity and the hypoxic ventilatory response (HVR)] in a manner consistent with natural age-related declines in hormones. Using barometric plethysmography, three experimental groups of female rats were assessed for HVR, chemosensitivity, and respiratory neural drive during progressive hypoxic challenges (FIO<sub>2</sub>: 0.15, 0.12, and 0.09): young (3-5 mos. old; in proestrus; n = 10), young OVX (3-5 mos. old; n = 10), and aged (>20 mos. old; n = 10). Our findings indicted that sex hormone loss did not appear to impact chemosensitivity or neural drive. Natural aging, but not OVX, resulted in decreased HVR as well as reduced magnitude in ventilatory output during stepwise hypoxia. Differences in metabolism were important to the interpretation of these results. Collectively, these data support the concept that aging impacts female respiratory function in complex and unique ways that differ from OVX.</p>","PeriodicalId":12477,"journal":{"name":"Frontiers in Physiology","volume":"15 ","pages":"1511960"},"PeriodicalIF":3.2,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11810928/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143398439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Frontiers in PhysiologyPub Date : 2025-01-28eCollection Date: 2025-01-01DOI: 10.3389/fphys.2025.1541639
Qianqian Chen, Yanfei Li, Xinchen Heng, Lei Zhao, Bin Wu
{"title":"The effects of 8 weeks of multi-directional movement training combined with balance training on the change of direction of young table tennis players.","authors":"Qianqian Chen, Yanfei Li, Xinchen Heng, Lei Zhao, Bin Wu","doi":"10.3389/fphys.2025.1541639","DOIUrl":"10.3389/fphys.2025.1541639","url":null,"abstract":"<p><strong>Background: </strong>Change of direction (COD) skills are crucial for athletic performance in sports such as table tennis. Improving COD can enhance overall agility and responsiveness during competition.</p><p><strong>Objective: </strong>To investigate the effects of an 8-week multi-directional movement training combined with balance training on the COD performance of young table tennis players.</p><p><strong>Methods: </strong>Thirty young table tennis players from the same team were randomly assigned to two groups: the multi-directional movement training combined with the balance training group (MB, n = 15) and the control group (CON, n = 15). The MB group underwent balance training on unstable surfaces, while the CON group performed the same balance exercises on stable ground. Both groups participated in the same multi-directional movement training program, which was conducted three times a week with 24-48 h of recovery between sessions for a duration of 8 weeks.</p><p><strong>Results: </strong>Significant group effects were observed in the modified agility test, non-dominant leg, dominant leg, and push block side lunge right test (p < 0.05). No significant group effects were found for the hexagon agility test, 3 m side slide test, A-movement test, or the whole table variable speed pendulum test (p > 0.05). Significant time-by-group interactions were noted for all variables (p < 0.05), indicating that improvements over time differed between the MB and CON groups. In the MB group, significant improvements were observed across all tests post-intervention, with high effect sizes (Partial η<sup>2</sup> values ranging from 0.361 to 0.815). In contrast, the CON group showed significant time effects in only a few tests, including the 3 m side slide test, A-movement test, modified agility test, and push block side lunge right test (p < 0.05), with no significant time effects for other variables.</p><p><strong>Conclusion: </strong>This study aimed to explore whether multi-directional movement training, when combined with balance exercises, could improve COD skills in young table tennis players. The results will inform future training strategies for enhancing agility and movement efficiency in table tennis athletes.</p>","PeriodicalId":12477,"journal":{"name":"Frontiers in Physiology","volume":"16 ","pages":"1541639"},"PeriodicalIF":3.2,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11811084/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143398471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}