Current research in physiology最新文献

{"title":"Effect of chest mobilization on intercostal muscle stiffness","authors":"Yu Yokoyama ,&nbsp;Taiki Kodesho ,&nbsp;Takuya Kato ,&nbsp;Gakuto Nakao ,&nbsp;Yuhei Saito ,&nbsp;Keigo Taniguchi","doi":"10.1016/j.crphys.2022.10.002","DOIUrl":"10.1016/j.crphys.2022.10.002","url":null,"abstract":"<div><p>This study examined the effect of chest mobilization on intercostal (IC) muscle stiffness using the IC muscle shear modulus. Sixteen healthy young men participated on two days with a minimum of 24 h between the stretching and control conditions (SC and CC). The tasks were resting breathing and deep breathing. The IC muscle shear modulus and muscle activity and rib cage circumference were measured before and after each condition. In the SC, IC stretching was performed for 1 min x 5 sets. In the CC, resting breathing, in a sitting position, was performed for 5 min. In the SC, the IC muscle shear modulus decreased significantly (p &lt; 0.05) at maximum inspiration in the deep breathing task, but there was no significant difference in the CC pre- and post-intervention. The results suggest that IC muscle stretching decreases IC muscle stiffness and improves muscle flexibility and that the IC muscle shear modulus may measure the effectiveness of chest mobilization.</p></div>","PeriodicalId":72753,"journal":{"name":"Current research in physiology","volume":"5 ","pages":"Pages 429-435"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/55/0d/main.PMC9713255.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35254875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteomic analysis of temperature-dependent developmental plasticity within the ventricle of juvenile Atlantic salmon (Salmo salar)","authors":"Carlie A. Muir,&nbsp;Bradley S. Bork,&nbsp;Bryan D. Neff,&nbsp;Sashko Damjanovski","doi":"10.1016/j.crphys.2022.07.005","DOIUrl":"10.1016/j.crphys.2022.07.005","url":null,"abstract":"<div><p>In teleosts, cardiac plasticity plays a central role in mediating thermal acclimation. Previously, we demonstrated that exposure to elevated temperatures throughout development (+4°C) improved acute thermal tolerance of the heart in juvenile Atlantic salmon. Fish raised in a warmer thermal regime also displayed higher proportions of compact myocardium within their ventricles. In the present study, we investigated the molecular mechanisms supporting this temperature-specific phenotype by comparing relative protein abundance in ventricular tissue from the same experimental fish using mass spectrometry. We provide the first description of the ventricular proteome in juvenile Atlantic salmon and identify 79 proteins displaying differential abundance between developmental treatments. The subset of proteins showing higher abundance in fish raised under elevated temperatures was significantly enriched for processes related to ventricular tissue morphogenesis, and changes in protein abundance support a hypertrophic model of compact myocardium growth. Proteins associated with the vasculature and angiogenesis also showed higher abundance in the warm-developmental group, suggesting capillarization of the compact myocardium in the hearts of these fish. Proteins related to oxidative metabolism and protein homeostasis also displayed substantive shifts in abundance between developmental treatments, underscoring the importance of these processes in mediating thermal plasticity of cardiac function. While rapid growth under warm developmental temperatures has been linked to cardiomyopathies in farmed salmon, markers of cardiac pathology were not implicated in the present study. Thus, our findings offer a molecular footprint for adaptive temperature-dependent plasticity within the ventricle of a juvenile salmonid.</p></div>","PeriodicalId":72753,"journal":{"name":"Current research in physiology","volume":"5 ","pages":"Pages 344-354"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/06/ac/main.PMC9403292.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33444855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of combined aerobic and resistance exercise on serum Klotho secretion in healthy young men -a pilot study-","authors":"Takuma Morishima ,&nbsp;Eisuke Ochi","doi":"10.1016/j.crphys.2022.06.001","DOIUrl":"10.1016/j.crphys.2022.06.001","url":null,"abstract":"<div><p>The impact of combined aerobic and resistance exercise on Klotho (KL) secretion is unclear. Twelve healthy young men completed two randomized experimental trials: 1) resistance exercise (RE) and 2) resistance exercise with prior aerobic exercise (AE + RE). Following baseline blood pressure assessment and blood collection, the subjects in the RE trial maintained a supine position for 45 min, while the subjects in the AE + RE trial performed 45 min of aerobic exercise. After 45 min of resting or aerobic exercise, all subjects performed resistance exercise. Following resistance exercise, the subjects rested in a supine position for 60 min. Blood pressure assessment and blood collection were repeated. Aerobic and resistance exercise significantly increased serum KL concentrations, respectively (P &lt; 0.05), and no additive effect of aerobic exercise on KL secretion was observed immediately after resistance exercise in the AE + RE trial compared with the RE trial. However, serum KL levels at 30 and 60 min after resistance exercise were significantly higher in the AE + RE trial than in the RE trial. Serum ET-1 concentrations were significantly increased only in the RE trial. In conclusion, combined aerobic and resistance exercise could maintain higher levels of serum KL secretion after exercise compared with resistance exercise only.</p></div>","PeriodicalId":72753,"journal":{"name":"Current research in physiology","volume":"5 ","pages":"Pages 246-250"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/0e/8a/main.PMC9218281.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40400823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Skipping the first active meal appears to adversely alter reproductive function in female than male rats","authors":"Oluwakemi T. Oyelowo,&nbsp;Emmanuel O. Taire,&nbsp;Olubunmi I. Ajao","doi":"10.1016/j.crphys.2022.10.001","DOIUrl":"10.1016/j.crphys.2022.10.001","url":null,"abstract":"<div><p>There is a growing consciousness about chrono-nutrition and its physiological functions. The human feeding pattern establishes three meals a day, meal timing however may not be adhered to. Previous studies have reported ovarian dysfunctions in breakfast skipping among females. In this study, the investigation was carried out on the effects of breakfast skipping on reproductive functions in the male rat and comparison, to the female rat. Eight-week-old animals (10 rats per group) were used to mimic post-adolescence. Rats are active at night thus the meal model was divided as follows. Female rats who had all three meals (Control_F), Female rats who had a no-first-active meal (NFAM_F), Male rats who had all three meals (Control_M), and Male rats who had a no-first-active meal (NFAM_M). All animals were fed the same amount of food every day. After the expiration of the four weeks experiment, serum testosterone, estrogen, Luteinising Hormone (LH) Follicle Stimulating Hormone (FSH), and prolactin (PRL) were quantified using ELISA. Sperm was also analyzed. There was a significant increase (p &lt; 0.05) in the testosterone level and sperm count in the NFAM_M compared to the Control_M while the estrogen level was significantly reduced in the NFAM_F compared to the Control_F. LH, FSH, and PRL levels were significantly reduced in the NFAM_F compared to the NFAM_M. These findings further confirm that post-adolescent females are prone to breakfast skipping. The increase in testosterone levels and sperm count in the males establish that breakfast skipping might not interfere with the reproductive physiology in males as it does in females.</p></div>","PeriodicalId":72753,"journal":{"name":"Current research in physiology","volume":"5 ","pages":"Pages 414-420"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/3f/1e/main.PMC9576489.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40561805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glucose uptake as an alternative to oxygen uptake for assessing metabolic rate in Danio rerio larvae","authors":"Bridget L. Evans ,&nbsp;Adam F.L. Hurlstone ,&nbsp;Peter E. Clayton ,&nbsp;Adam Stevens ,&nbsp;Holly A. Shiels","doi":"10.1016/j.crphys.2022.05.002","DOIUrl":"10.1016/j.crphys.2022.05.002","url":null,"abstract":"<div><p>Respirometry, based on oxygen uptake, is commonly employed for measuring metabolic rate. There is a growing need for metabolic rate measurements suitable for developmental studies, particularly in <em>Danio rerio</em>, where many important developmental stages occur at &lt; 4 mm. However, respirometry becomes more challenging as the size of the organism reduces. Additionally, respirometry can be costly and require significant experience and technical knowledge which may prohibit uptake in non-specialist/non-physiology labs. Thus, using equipment routine in most developmental/molecular biology laboratories, we measured glucose uptake in 96-h post fertilisation (hpf) zebrafish larvae and compared it to stop-flow respirometry measures of oxygen uptake to test whether glucose uptake was a suitable alternative measure of metabolic rate. A Passing-Bablok regression revealed that within a 95% limit of agreement, the rate of glucose uptake and the rate of oxygen uptake were equivalent as measures of metabolic rate in 96 hpf <em>Danio rerio</em> larvae. Thus, the methodology we outline here may be a useful alternative or a complementary method for assessing metabolic rate in small organisms.</p></div>","PeriodicalId":72753,"journal":{"name":"Current research in physiology","volume":"5 ","pages":"Pages 216-223"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2665944122000219/pdfft?md5=6901516fc7155a449eab9603dba411a5&pid=1-s2.0-S2665944122000219-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43733117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of an autism-associated KCNMB2 variant, G124R, on BK channel properties","authors":"Hans J. Moldenhauer ,&nbsp;Ria L. Dinsdale ,&nbsp;Sara Alvarez ,&nbsp;Alberto Fernández-Jaén ,&nbsp;Andrea L. Meredith","doi":"10.1016/j.crphys.2022.09.001","DOIUrl":"10.1016/j.crphys.2022.09.001","url":null,"abstract":"<div><p>BK K⁺ channels are critical regulators of neuron and muscle excitability, comprised of a tetramer of pore-forming αsubunits from the <em>KCNMA1</em> gene and cell- and tissue-selective β subunits (<em>KCNMB1-4</em>). Mutations in <em>KCNMA1</em> are associated with neurological disorders, including autism. However, little is known about the role of neuronal BK channel β subunits in human neuropathology. The β2 subunit is expressed in central neurons and imparts inactivation to BK channels, as well as altering activation and deactivation gating. In this study, we report the functional effect of G124R, a novel <em>KCNMB2</em> mutation obtained from whole-exome sequencing of a patient diagnosed with autism spectrum disorder. Residue G124, located in the extracellular loop between TM1 and TM2, is conserved across species, and the G124R missense mutation is predicted deleterious with computational tools. To investigate the pathogenicity potential, BK channels were co-expressed with β2^WT and β2^G124R subunits in HEK293T cells. BK/β2 currents were assessed from inside-out patches under physiological K⁺ conditions (140/6 mM K⁺ and 10 μM Ca²⁺) during activation and inactivation (voltage-dependence and kinetics). Using β2 subunits lacking inactivation (β2IR) revealed that currents from BK/β2IR^G124R channels activated 2-fold faster and deactivated 2-fold slower compared with currents from BK/β2IR^WT channels, with no change in the voltage-dependence of activation (V_1/2). Despite the changes in the BK channel opening and closing, BK/β2^G124R inactivation rates (τ_inact and τ_recovery), and the V_1/2 of inactivation, were unaltered compared with BK/β2^WT channels under standard steady-state voltage protocols. Action potential-evoked current was also unchanged. Thus, the mutant phenotype suggests the β2^G124R TM1-TM2 extracellular loop could regulate BK channel activation and deactivation kinetics. However, additional evidence is needed to validate pathogenicity for this patient-associated variant in <em>KCNMB</em>2.</p></div>","PeriodicalId":72753,"journal":{"name":"Current research in physiology","volume":"5 ","pages":"Pages 404-413"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/e6/fe/main.PMC9531041.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33490748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Empagliflozin restores cardiac metabolic flexibility in diet-induced obese C57BL6/J mice","authors":"Bingxian Xie ,&nbsp;Wesley Ramirez ,&nbsp;Amanda M. Mills ,&nbsp;Brydie R. Huckestein ,&nbsp;Moira Anderson ,&nbsp;Martha M. Pangburn ,&nbsp;Eric Y. Lang ,&nbsp;Steven J. Mullet ,&nbsp;Byron W. Chuan ,&nbsp;Lanping Guo ,&nbsp;Ian Sipula ,&nbsp;Christopher P. O'Donnell ,&nbsp;Stacy G. Wendell ,&nbsp;Iain Scott ,&nbsp;Michael J. Jurczak","doi":"10.1016/j.crphys.2022.05.003","DOIUrl":"10.1016/j.crphys.2022.05.003","url":null,"abstract":"<div><p>Sodium-glucose co-transporter type 2 (SGLT2) inhibitor therapy to treat type 2 diabetes unexpectedly reduced all-cause mortality and hospitalization due to heart failure in several large-scale clinical trials, and has since been shown to produce similar cardiovascular disease-protective effects in patients without diabetes. How SGLT2 inhibitor therapy improves cardiovascular disease outcomes remains incompletely understood. Metabolic flexibility refers to the ability of a cell or organ to adjust its use of metabolic substrates, such as glucose or fatty acids, in response to physiological or pathophysiological conditions, and is a feature of a healthy heart that may be lost during diabetic cardiomyopathy and in the failing heart. We therefore undertook studies to determine the effects of SGLT2 inhibitor therapy on cardiac metabolic flexibility <em>in vivo</em> in obese, insulin resistant mice using a [U¹³C]-glucose infusion during fasting and hyperinsulinemic euglycemic clamp. Relative rates of cardiac glucose versus fatty acid use during fasting were unaffected by EMPA, whereas insulin-stimulated rates of glucose use were significantly increased by EMPA, alongside significant improvements in cardiac insulin signaling. These metabolic effects of EMPA were associated with reduced cardiac hypertrophy and protection from ischemia. These observations suggest that the cardiovascular disease-protective effects of SGLT2 inhibitors may in part be explained by beneficial effects on cardiac metabolic substrate selection.</p></div>","PeriodicalId":72753,"journal":{"name":"Current research in physiology","volume":"5 ","pages":"Pages 232-239"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2665944122000220/pdfft?md5=ee7889519743c8106df5cf472933d5b5&pid=1-s2.0-S2665944122000220-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45017483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The influence of external stressors on physiological testing: Implication for return-to-play protocols","authors":"Chase J. Ellingson ,&nbsp;Jyotpal Singh ,&nbsp;Cody A. Ellingson ,&nbsp;Ryan Dech ,&nbsp;Jaroslaw Piskorski ,&nbsp;J. Patrick Neary","doi":"10.1016/j.crphys.2022.06.003","DOIUrl":"10.1016/j.crphys.2022.06.003","url":null,"abstract":"<div><p>External stressors such as alcohol, caffeine, and vigorous exercise are known to alter cellular homeostasis, affecting the autonomic nervous system (ANS) and overall physiological function. However, little direct evidence exists quantifying the impact of these external stressors on physiological testing. We assessed the impact of the above-listed stressors on spontaneous baroreflex sensitivity (BRS), heart rate variability (HRV), heart rate asymmetry (HRA), and systolic blood pressure variability (BPV). Seventeen male university varsity American-style football athletes completed two identical assessments on separate days, once presenting with one or more stressors (recent intake of caffeine, alcohol, or exercise participation; contraindicated assessment) and another with no stressors present (repeat assessment). Both assessments were conducted within one week and at the same time of day. The testing protocol consisted of 5-min of rest followed by 5-min of a squat-stand maneuver (0.05 Hz). Continuous beat-to-beat blood pressure and electrocardiogram measurements were collected and allowed for calculations of BRS, HRV, HRA, and BPV. Significant decreases (p &lt; 0.05) in HRV and HRA metrics (SDNN, SD2, SDNNd, SDNNa, SD2a, SD2d), HRV total power, and BRS-up sequence were found during the contraindicated assessment in comparison to the repeat assessment. When assessing those with exercise as their only stressor, high-frequency HRV and BRS-pooled were significantly decreased and increased, respectively, during the contraindicated assessment. Pre-season physiological baseline testing in sport is becoming increasingly prevalent and thus must consider external stressors to ascertain accurate and reliable data. This data confirms the need for stringent and standardized guidelines for pre-participation baseline physiological testing.</p></div>","PeriodicalId":72753,"journal":{"name":"Current research in physiology","volume":"5 ","pages":"Pages 240-245"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/d7/3b/main.PMC9213225.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40400822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elucidating the combined effect of intermittent hypoxia training and acetazolamide on hypoxia induced hematological and physiological changes","authors":"Megha A. Nimje ,&nbsp;Himadri Patir ,&nbsp;Rajeshkumar Tirpude ,&nbsp;Bhuvnesh Kumar","doi":"10.1016/j.crphys.2022.07.004","DOIUrl":"10.1016/j.crphys.2022.07.004","url":null,"abstract":"<div><p>As the number of people travelling to altitude increases, the risk of life threatening medical emergencies also increases. It is important that we have effective strategies to minimize the risk of altitude illness. In this study, an attempt was made to investigate the combined effect of non-pharmacological (Intermittent hypoxia training; IHT) and pharmacological (acetazolamide; ACZ) intervention as a prophylactic strategy in order to minimize the risk of high altitude hypoxic related problems using rats as an animal model. Male Sprague Dawley rats were subjected to IHT for 4 h consecutively for 5 days at 12% FiO₂ under normobaric conditions with and without oral ACZ administration at 25 mg/kg body weight. Validation of the intervention was performed by exposing the rats to extreme hypoxia (EH) at 8% FiO₂ to further assess the effect of IHT and ACZ on hypoxic acclimatization. The principal findings of this study is that the combined effect of IHT and ACZ improves the arterial oxygenation by alterations in hemodynamics and in blood gasometry, thereby resulting into an increase in the oxygen carrying capacity of the blood with increase in SpO₂ (peripheral oxygen saturation). The present study showed that the combined effect of IHT with ACZ could be refined as a prophylactic measure for better outcomes during altitude ascent and rapid altitude acclimatization rather than IHT or ACZ alone.</p></div>","PeriodicalId":72753,"journal":{"name":"Current research in physiology","volume":"5 ","pages":"Pages 327-337"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9307424/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40625926","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A New Prospect for the Treatment of Nephrotic Syndrome Based on Network Pharmacology Analysis","authors":"Rini Varghese,&nbsp;Anuradha Majumdar","doi":"10.1016/j.crphys.2021.12.004","DOIUrl":"10.1016/j.crphys.2021.12.004","url":null,"abstract":"<div><p>Network pharmacology is an emerging field which is currently capturing interest in drug discovery and development. Chronic kidney conditions have become a threat globally due to its associated lifelong therapies. Nephrotic syndrome (NS) is a common glomerular disease that is seen in paediatric and adult population with characteristic manifestation of proteinuria, oedema, hypoalbuminemia, and hyperlipidemia. It involves podocyte damage with tubulointerstitial fibrosis and glomerulosclerosis. Till date there has been no specific treatment available for this condition that provides complete remission. Repurposing of drugs can thus be a potential strategy for the treatment of NS. Recently, epigenetic mechanisms were identified that promote progression of many renal diseases. Therefore, in the present study, we investigated two epigenetic drugs valproic acid (VPA) and all-trans retinoic acid (ATRA). Epigenetic drugs act by binging about changes in gene expression without altering the DNA sequence. The changes include DNA methylation or histone modifications. The targets for the two drugs ATRA and VPA were collated from ChEMBL and Binding DB. All the genes associated with NS were collected from DisGeNET and KEGG database. Interacting proteins for the target genes were acquired from STRING database. The genes were then subjected to gene ontology and pathway enrichment analysis using a functional enrichment software tool. A drug-target and drug-potential target-protein interaction network was constructed using the Cytoscape software. Our results revealed that the two drugs VPA and ATRA had 65 common targets that contributed to kidney diseases. Out of which, 25 targets were specifically NS associated. Further, our work exhibited that ATRA and VPA were synergistically involved in pathways of inflammation, renal fibrosis, glomerulosclerosis and possibly mitochondrial biogenesis and endoplasmic reticulum stress. We thus propose a synergistic potential of the two drugs for treating chronic kidney diseases, specifically NS. The outcomes will undoubtedly invigorate further preclinical and clinical explorative studies. We identify network pharmacology as an initial inherent approach in identifying drug candidates for repurposing and synergism.</p></div>","PeriodicalId":72753,"journal":{"name":"Current research in physiology","volume":"5 ","pages":"Pages 36-47"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/1f/9c/main.PMC8783131.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39735654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}