{"title":"Naringenin protects myocardial ischemia/reperfusion injury by regulating miR-24-3p to inhibit cell death-inducing p53 target 1 expression.","authors":"Xiao Jin, Ling Jin, Bingxin Wu, Danping Xu","doi":"10.4149/gpb_2023035","DOIUrl":"10.4149/gpb_2023035","url":null,"abstract":"<p><p>Myocardial ischemia/reperfusion (I/R) causes serious threats to human life. Naringenin, a polyphenolic compound naturally occurring in citrus fruit, has cardioprotective effects against myocardial I/R injury. Besides, miR-24-3p is also reported to have cardioprotective effects. We intended to explore whether the cardioprotective effects of naringenin relate to miR-24-3p and its underlying mechanism. In this study, we used an in vivo rat myocardial I/R model and an in vitro cardiomyocyte H9c2 hypoxia/reoxygenation (H/R) model. Myocardial injury was detected by hematoxylin-eosin staining and ELISA for creatine kinase (CK), malondialdehyde (MDA), and lactate dehydrogenase (LDH). miR-24-3p and cell death inducing p53 target 1 (Cdip1) mRNA expressions were examined by RT-PCR. We find that naringenin pretreatment significantly relieves myocardial I/R injury, reduces LDH, CD, and MDA levels, and increases miR-24-3p expression. Furthermore, miR-24-3p alleviates myocardial I/R injury partially through regulating Cdip1. Moreover, naringenin protects myocardial I/R injury partially by regulating miR-24-3p to inhibit Cdip1 expression. In conclusion, our data suggest naringenin protects myocardial I/R injury partially through miR-24-3p/Cdip1 axis.</p>","PeriodicalId":12514,"journal":{"name":"General physiology and biophysics","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139680989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kyeong-Eon Park, SooHee Lee, Sung Il Bae, Yeran Hwang, Seong-Ho Ok, Seung Hyun Ahn, Gyujin Sim, Soonghee Chung, Ju-Tae Sohn
{"title":"Theophylline-induced endothelium-dependent vasodilation is mediated by increased nitric oxide release and phosphodiesterase inhibition in rat aorta.","authors":"Kyeong-Eon Park, SooHee Lee, Sung Il Bae, Yeran Hwang, Seong-Ho Ok, Seung Hyun Ahn, Gyujin Sim, Soonghee Chung, Ju-Tae Sohn","doi":"10.4149/gpb_2023023","DOIUrl":"10.4149/gpb_2023023","url":null,"abstract":"<p><p>This study aimed to examine the endothelial dependence of vasodilation induced by the phosphodiesterase inhibitor theophylline in isolated rat thoracic aortas and elucidate the underlying mechanism, with emphasis on endothelial nitric oxide (NO). The effects of various inhibitors and endothelial denudation on theophylline-induced vasodilation, and the effect of theophylline on vasodilation induced by NO donor sodium nitroprusside, cyclic guanosine monophosphate (cGMP) analog bromo-cGMP, and β-agonist isoproterenol in endothelium-denuded aorta were examined. The effects of theophylline and sodium nitroprusside on cGMP formation were also examined. We examined the effect of theophylline on endothelial nitric oxide synthase (eNOS) phosphorylation and intracellular calcium levels. Theophylline-induced vasodilation was greater in endothelium-intact aortas than that in endothelium-denuded aortas. The NOS inhibitor, NW-nitro-L-arginine methyl ester; non-specific guanylate cyclase (GC) inhibitor, methylene blue; and NO-sensitive GC inhibitor, 1H-[1,2,4]oxadiazolo[4,3-a] quinoxalin-1-one inhibited theophylline-induced vasodilation in endothelium-intact aortas. Theophylline increased the vasodilation induced by sodium nitroprusside, bromo-cGMP, and isoproterenol. Theophylline increased cGMP formation in endothelium-intact aortas, and sodium nitroprusside-induced cGMP formation in endothelium-denuded aortas. Moreover, theophylline increased stimulatory eNOS (Ser1177) phosphorylation and endothelial calcium levels, but decreased the phosphorylation of inhibitory eNOS (Thr495). These results suggested that theophylline-induced endothelium-dependent vasodilation was mediated by increased endothelial NO release and phosphodiesterase inhibition.</p>","PeriodicalId":12514,"journal":{"name":"General physiology and biophysics","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49676375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Daniela Vargová, Ján Dargaj, Soňa Fraňová, Matúš Dohál, Ján Ľupták, Ján Švihra, Lukáš Briš, Marián Grendár, Martina Šutovská
{"title":"Immunobiochemical profile of clear cell renal cell carcinoma (ccRCC): A preliminary study.","authors":"Daniela Vargová, Ján Dargaj, Soňa Fraňová, Matúš Dohál, Ján Ľupták, Ján Švihra, Lukáš Briš, Marián Grendár, Martina Šutovská","doi":"10.4149/gpb_2023015","DOIUrl":"https://doi.org/10.4149/gpb_2023015","url":null,"abstract":"<p><p>Clear cell renal cell carcinoma (ccRCC) is the most common variant of RCC. It is an aggressive disease with an unfavorable prognosis. The rich immune infiltrates present in the tumor microenvironment (TME) of ccRCC produce various signaling molecules, especially cytokines, which primarily activate the Jak/STAT pathway and significantly influence tumor pathogenesis. STAT3 has a well-defined oncogenic character. Using multiplex assays and ELISA, we have measured the concentrations of 27 cytokines and STAT3 in tumor and healthy renal tissue from 16 patients with histologically verified ccRCC. We have detected significantly higher levels of G-CSF, IL-6, CXCL10, CCL3, and CCL4 in tumor tissue than in their healthy counterparts. There were significant differences in the levels of IL-1β and PDGF-BB between tumors of different nuclear grades (NG). Intratumoral IL-12p70 and IL-15 showed a significant positive correlation with intratumoral STAT3. The concentration of STAT3 in tumors was significantly lower than in the kidney. An increase in tumor STAT3 levels was associated with an increase in the pathological stage of the disease (TNM), but not with NG. The results of our study confirm the significant role of various cytokines and STAT3 in the pathogenesis of ccRCC and indicate their clinical relevance.</p>","PeriodicalId":12514,"journal":{"name":"General physiology and biophysics","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10233842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gangpu Wang, Zhiqian Liu, Qi Wang, Bingqi Liu, Jie Li
{"title":"Clinical and prognostic significance of CCPG1 in hepatocellular carcinoma.","authors":"Gangpu Wang, Zhiqian Liu, Qi Wang, Bingqi Liu, Jie Li","doi":"10.4149/gpb_2023017","DOIUrl":"https://doi.org/10.4149/gpb_2023017","url":null,"abstract":"<p><p>This study aimed to examine the clinical and prognostic significance of cell-cycle progression gene 1 (CCPG1) in hepatocellular carcinoma (HCC). We firstly analyzed CCPG1 expression in various cancers using The Cancer Genome Atlas and the Genotype-Tissue Expression project databases. The relative expression levels of CCPG1 were determined in 164 paired HCC and adjacent tissues using immunohistochemistry. The correlation between CCPG1 and clinicopathological characteristics of HCC was analyzed. Cox proportional models were used to identify the prognostic factors for overall survival (OS) and disease-free survival (DFS). The expression of CCPG1 was lower in HCC tissues than in adjacent non-tumor liver tissues. The expression of CCPG1 was significantly correlated with tumor number (p = 0.02) and tumor differentiation (p = 0.04) in HCC. Lower expression of CCPG1 in HCC patients was associated with poor OS and DFS (p < 0.01). Relative low expression of CCPG1 in HCC is significantly correlated with the poor prognosis of HCC patients after surgical resection, suggesting its possible role as a potential prognostic marker for HCC.</p>","PeriodicalId":12514,"journal":{"name":"General physiology and biophysics","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10259497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Petronela Rezbarikova, Jana Viskupicova, Magdalena Majekova, Lubica Horakova
{"title":"Interaction of quercetin and its derivatives with Ca2+-ATPase from sarcoplasmic reticulum: Kinetic and molecular modeling studies.","authors":"Petronela Rezbarikova, Jana Viskupicova, Magdalena Majekova, Lubica Horakova","doi":"10.4149/gpb_2023020","DOIUrl":"https://doi.org/10.4149/gpb_2023020","url":null,"abstract":"<p><p>Sarcoplasmic reticulum Ca2+-ATPases (SERCAs) regulate cellular calcium homeostasis and are targeted for age-related diseases. Among 14 SERCA mRNA splice variants, SERCA1a is specific to adult fast-twitch skeletal muscle. Quercetin derivatives (monochloropivaloylquercetin (CPQ), IC50 = 195.7 µM; 2-chloro-1,4-naphthoquinonequercetin (CHNQ), IC50 = 60.3 µM) were studied for their impact on SERCA1a using molecular modeling and enzyme kinetics. While there were some similarities in kinetic parameters and molecular modeling, the compounds exhibited diverse actions on SERCA1a. Quercetin reduced activity by 48% at 250 μM by binding to the cytosolic ATP-binding pocket with increased ATP affinity. CPQ bound near the Ca2+-binding site, possibly altering the transmembrane domain. CHNQ significantly reduced activity by 94% at 250 μM without binding to substrate sites. It was proposed that CHNQ induced global protein structure changes, inhibiting Ca2+-ATPase activity.</p>","PeriodicalId":12514,"journal":{"name":"General physiology and biophysics","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10233840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pengfei Lu, Kadeliya Yushan, Gulimilai Yusufu, Hiu Wang, Rui Mao
{"title":"Correlation of microsatellite status and EBV infection with clinical characteristics of patients with gastric cancer.","authors":"Pengfei Lu, Kadeliya Yushan, Gulimilai Yusufu, Hiu Wang, Rui Mao","doi":"10.4149/gpb_2023021","DOIUrl":"https://doi.org/10.4149/gpb_2023021","url":null,"abstract":"<p><p>This study was designed to investigate the correlation of microsatellite status (MS) and Epstein-Barr virus (EBV) infection with the clinical characteristics of gastric cancer (GC) patients. MS was detected by immunohistochemistry. EBV was detected by in situ hybridization. There were 31.3% cases showed mismatch repair-deficient (dMMR)/ microsatellite instability (MSI) and 68.7% cases showed mismatch repair-proficient (pMMR)/ microsatellite stability (MSS). The dMMR/MSI was more common in the elderly, in patients with cardia GC, smaller tumor diameter or non-poorly differentiated carcinoma. The survival in dMMR/MSI patients tended to be longer than that in pMMR/MSS patients. Total 7.6% cases showed EBV-positive (EBV(+)) among 198 GC patients. EBV(+) was more common in patients with advanced GC or poorly differentiated adenocarcinoma. MSI was more common in EBV-negative (EBV(-)) patients than in EBV(+) patients. The dMMR/MSI patients with stage II GC benefited from chemotherapy. The survival of EBV(+) patients tended to be longer than that of EBV(-) patients.</p>","PeriodicalId":12514,"journal":{"name":"General physiology and biophysics","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10233844","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yanli Xu, Xiaodi Kang, Huafang Liu, Hongli Jiang, Wenjing Wang
{"title":"LncRNA XIST promotes insulin resistance in gestational diabetes mellitus via the microRNA-181b-5p/NDRG2 axis.","authors":"Yanli Xu, Xiaodi Kang, Huafang Liu, Hongli Jiang, Wenjing Wang","doi":"10.4149/gpb_2023019","DOIUrl":"https://doi.org/10.4149/gpb_2023019","url":null,"abstract":"<p><p>Many studies have explored the role of lncRNA X inactivation-specific transcript (XIST) in diabetes. This study was designed to unravel the regulatory mechanism of XIST on animal models of gestational diabetes mellitus (GDM) progression via the microRNA (miR)-181b-5p/N-myc downstream-regulated gene 2 (NDRG2) axis. XIST, miR-181b-5p, and NDRG2 expression levels in GDM mice were detected. The GDM mice were subjected to gain- and loss-of-function assays to examine the change of glucose metabolism indices (fasting blood glucose (FBG), fasting insulin (FINS) and homeostasis model assessment of insulin resistance (HOMA-IR)), serum oxidative stress factors (glutathione (GSH), superoxide dismutase (SOD), and malondialdehyde (MDA)), serum inflammatory factors (interleukin-1 β (IL-1β), IL-6, and tumor necrosis factor α (TNF-α)), pathological changes of pancreatic tissues, and apoptotic cells in pancreatic islets in GDM mice. XIST and NDRG2 expression were elevated while miR-181b-5p expression was depleted in GDM mice. Down-regulated XIST or NDRG2 or up-regulated miR-181b-5p reduced the FBG level, HOMA-IR, and serum IL-1β, IL-6, and TNF-α, and MDA contents, elevated the FINS, GSH, and SOD level, mitigated pathological changes in pancreatic tissues, and decelerated apoptotic cells in pancreatic islets in GDM mice. Silenced XIST dampens insulin resistance in GDM mice via the modulation of the miR-181b-5p/NDRG2 axis.</p>","PeriodicalId":12514,"journal":{"name":"General physiology and biophysics","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10233843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Songlin Zhang, Hang Xie, Yajuan Du, Boxiang Wang, Beidi Lan, Haiyan Wang
{"title":"DNMT1-induced miR-133b suppression via methylation promotes myocardial fibrosis after myocardial infarction.","authors":"Songlin Zhang, Hang Xie, Yajuan Du, Boxiang Wang, Beidi Lan, Haiyan Wang","doi":"10.4149/gpb_2023018","DOIUrl":"https://doi.org/10.4149/gpb_2023018","url":null,"abstract":"<p><p>Myocardial fibrosis is an underlying cause of many cardiovascular diseases. Novel insights into the epigenetic control of myocardial fibrosis are now emerging. The current work is focused on investigating the biological role of DNA methyltransferase 1 (DNMT1) in myocardial fibrosis as well as the underlying mechanism. Our findings revealed that DNMT1 expression levels were upregulated, whereas miR-133b expression levels were decreased in a rat model of myocardial fibrosis following myocardial infarction. In vitro, the expression levels of DNMT1 increased and those of miR-133b decreased after Ang-II treatment in cardiac fibroblasts. DNMT1 knockdown inhibited Ang-II-induced cardiac myofibroblast activation, and DNMT1 overexpression increased the proliferation and collagen generation of cardiac myofibroblasts. Furthermore, DNMT1 expression levels decreased, while miR-133b expression levels increased after treatment with 5-Aza (5-Azacytidine, a known inhibitor of DNA methylation) in Ang-II-induced cardiac fibroblasts. BSP (Bisulfite sequencing PCR) results showed a marked decrease in methylation levels in the miR-133b promoter region upon overexpression of DNMT1, whereas knockdown of DNMT1 blocked increased methylation levels in the miR-133b promoter region in Ang-II-induced cardiac fibroblasts. Finally, 5-Aza treatment reduced the progression of myocardial fibrosis after myocardial infarction in rats in vivo. Collectively, our results suggest that DNMT1 mediates CTGF expression in cardiac fibroblast activation by regulating the methylation of miR-133b. The present work reveals the unique role of the DNMT1/miR-133b/CTGF axis in myocardial fibrosis, thus suggesting its great therapeutic potential in the treatment of cardiac diseases.</p>","PeriodicalId":12514,"journal":{"name":"General physiology and biophysics","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10259505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Juraj Pivko, Alexander Makarevich, Lucia Olexiková, Elena Kubovičová, Peter Makovický, Linda Dujičková, Jiří Bezdíček
{"title":"The morphological and functional ultrastructure of cells in pre-implantation embryos.","authors":"Juraj Pivko, Alexander Makarevich, Lucia Olexiková, Elena Kubovičová, Peter Makovický, Linda Dujičková, Jiří Bezdíček","doi":"10.4149/gpb_2023011","DOIUrl":"https://doi.org/10.4149/gpb_2023011","url":null,"abstract":"<p><p>Cells of pre-implantation embryos are equipped with many morphological and functional systems through which they can synthesize specific proteins and effectively ensure the protection of early embryonic development. Here we present evidence for the existence of these systems in morphologically normal and abnormal bovine blastocyst stage embryos in vivo at the ultrastructural and actin cytoskeleton levels. The appearance of organelles in the trophectoderm (TE) and inner cell mass (ICM) cells, responsible for their synthetic activities and their role in the development of early bovine embryos are described. We point out the importance of endocytic processes and the participation of extracellular vesicles in the formation of intercellular contacts and homeostasis of the embryo microenvironment. Several changes in the ultrastructural morphology of embryos produced by different methods (ICSI, parthenogenetic AC/DC electrical activation, IVF with separated sperm) and freezing/thawed embryos are described. We also show alterations occurred in the organelles after viral contamination of embryos with BHV-1 and BVDV viruses, and in embryos from over-conditioned cows. Recorded changes in organelles and appearance of cellular autophagic structures (vesicles, multivesicular bodies and autophagolysosomes) may negatively affect embryo metabolism and lead to the emergence of pathological processes in TE and ICM cells of preimplantation embryos.</p>","PeriodicalId":12514,"journal":{"name":"General physiology and biophysics","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9820975","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Martina Martinikova, Robert Ruzinak, Egon Kurca, Michael Teodor Grey, Stefan Sivak
{"title":"Biomedical research brings mTBI biomarkers a step closer to the bedside - implementation in clinical practice.","authors":"Martina Martinikova, Robert Ruzinak, Egon Kurca, Michael Teodor Grey, Stefan Sivak","doi":"10.4149/gpb_2023013","DOIUrl":"https://doi.org/10.4149/gpb_2023013","url":null,"abstract":"<p><p>Research in the field of TBI (traumatic brain injury) has long been focused on severe brain injury, while the number of mild injuries far overweigh severe injuries. Mild head injuries constitute up to 95% of all traumatic head injuries. The purpose of this work is to identify mTBI (mild traumatic brain injury) patients who are unlikely to benefit from CT (computed tomography) scanning. Biomarkers capable of clearly discriminating between CT-positive and CT-negative subjects are needed. Biomarkers hold the potential to document whether a concussion occurred, especially when the history is unclear and neurocognitive sequelae persist. Recently, following advances in proteomics analysis, investigators have introduced ubiquitin C-terminal hydrolase-L1 (UCH-L1) and glial fibrillary acidic protein (GFAP) as two promising brain injury biomarkers. The authors provide an update on the current knowledge of TBI biomarkers, especially protein biomarkers for neuronal cell body injury (UCH-L1) and astroglial injury (GFAP, S100B), and a focused literature review dealing with implementation of mTBI biomarkers in clinical practice.</p>","PeriodicalId":12514,"journal":{"name":"General physiology and biophysics","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9820977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}