{"title":"CircRSU1 alleviates LPS-induced human pulmonary microvascular endothelial cell injury by targeting miR-1224-5p/ITGA5 axis.","authors":"Yongtao Cheng, Fenggong Wang, Cui Guo, Shenghua Yuan, Jianzhong Li, Yuangang Zhang","doi":"10.4149/gpb_2023031","DOIUrl":"10.4149/gpb_2023031","url":null,"abstract":"<p><p>To investigate the potential functions and regulatory mechanism of circRSU1 on septic acute lung injury (sepsis-ALI) progression. We used lipopolysaccharide (LPS)-stimulated human pulmonary microvascular endothelial cells (HPMECs) to establish the cell model of sepsis-ALI in vitro. qRT-PCR and Western blotting were used for the detection of genes and proteins. The migration and tubulogenesis of HPMECs were assessed by transwell, wound healing, and tube formation assays. Inflammatory factors were detected by ELISA analysis. Cell permeability (PA) was determined by transendothelial resistance (TEER) and fluorescein isothiocyanate (FITC) with transwell assay. The interaction between miR-1224-5p and circRSU1 or ITGA5 (Integrin Subunit Alpha 5) was studied by dual-luciferase reporter and RNA pull-down assays. CircRSU1 expression was decreased after LPS treatment in HPMECs. Functionally, re-expression of circRSU1 in HPMECs could alleviate LPS-induced inflammatory response, the inhibition of cell migration and tube formation and enhancement of cell permeability. Mechanistically, circRSU1 acted as a sponge for miR-1224-5p. LPS treatment enhanced miR-1224-5p expression, and inhibition of miR-1224-5p reversed LPS-evoked HPMEC dysfunction mentioned above. Moreover, miR-1224-5p could abolish the protective effects of circRSU1 on HPMECs. In addition, miR-1224-5p directly targeted ITGA5, and circRSU1 was able to regulate ITGA5 expression via interacting with miR-1224-5p. CircRSU1 could alleviate LPS-induced HPMEC injury by miR-1224-5p/ITGA5 axis, indicating the potential molecular contribution of circRSU1 in sepsis-ALI.</p>","PeriodicalId":12514,"journal":{"name":"General physiology and biophysics","volume":"43 1","pages":"1-11"},"PeriodicalIF":1.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139680983","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}
{"title":"Combination therapy of metformin and atorvastatin against benzopyrene-induced lung cancer via inflammatory signaling pathway.","authors":"Xuecong Ning, Shusen Zhang, Zhiguo Gao, Aimin Li","doi":"10.4149/gpb_2023030","DOIUrl":"10.4149/gpb_2023030","url":null,"abstract":"<p><p>The most prevalent cause of lung cancer is smoking tobacco, but exposure to second hand smoke, air pollution, and certain chemicals and substances at work can also raise the risk of disease. In this study, we scrutinized the chemoprotective effect of the metformin and atorvastatin combination against benzo[a]pyrene (BaP)-induced lung cancer in mice of Swiss albino. BaP (50 mg/kg) was used for induction of lung cancer and mice were treated with metformin, atorvastatin or their combination. Metformin + atorvastatin combination significantly (p< 0.001) improved the body weight, liver weight, suppressed the lung weight and tumor incidence and altered the levels of immunocompetent cells, polyamines, lung tumor markers, lung parameters and antioxidant parameters, respectively. Metformin + atorvastatin combination also suppressed cytokines levels, inflammatory parameters and caspase parameters. On the basis of the results, we can conclude that metformin + atorvastatin combination remarkably suppressed lung cancer via the inflammatory pathway.</p>","PeriodicalId":12514,"journal":{"name":"General physiology and biophysics","volume":"43 1","pages":"57-71"},"PeriodicalIF":1.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139680984","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}
Mária Makovická, Adela Vrbenská, Peter Makovický, Barbora Durcová, Jozef Škarda, Vojtěch Kamarád, Mária Miklošová, Kvetoslava Rimárová, Patricie Michalčová, Klaudia Kráľová, Jozef Muri
{"title":"Histopathological findings in lung biopsies with usual interstitial pneumonia: Definition of a new classification score for histological fibrotic stages.","authors":"Mária Makovická, Adela Vrbenská, Peter Makovický, Barbora Durcová, Jozef Škarda, Vojtěch Kamarád, Mária Miklošová, Kvetoslava Rimárová, Patricie Michalčová, Klaudia Kráľová, Jozef Muri","doi":"10.4149/gpb_2023029","DOIUrl":"10.4149/gpb_2023029","url":null,"abstract":"<p><p>The objective of this article is to describe and classify usual interstitial pneumonia (UIP) changes according to their relevance in the pathology of the idiopathic pulmonary fibrosis (IPF) process. In a cohort of 50 patients (25♀, 25♂) with UIP findings, the percentage ratio between fibrotic and preserved parts of the lungs was quantified. Three quantitative stages of fibrotic involvement of the lung parenchyma and concomitant changes were defined. These are initial (≤20%), advanced (21-40%), and diffuse (≥41%) fibrosis of the lungs. Histologically, temporal heterogeneity is predominant with thickened alveolar septa, interstitial fibrosis, and the presence of fibroblastic foci up to mature diffuse fibrosis with honeycomb changes. The finding is accompanied by variably mature lymphocytic inflammation, presence of macrophages, emphysema, bronchioloectasia of the alveoli, bronchiectasis, bronchial muscle wall hypertrophy, hypertrophy of the vessel walls, alveolar mucosa, focal haemorrhage, and hyalinization of the lungs. Pneumocyte hyperplasia, occasionally atypical in appearance with hobnail changes, as well as squamous metaplasia are observed. In the methodically quantified stages of fibrous involvement, 14 subjects were classified (6♀, 8♂) into the stage of initial fibrosis, 21 subjects (11♀; 10♂) into the stage of advanced fibrosis, and 15 subjects (8♀; 7♂) into the stage of diffuse fibrosis.</p>","PeriodicalId":12514,"journal":{"name":"General physiology and biophysics","volume":"43 1","pages":"49-55"},"PeriodicalIF":1.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139680986","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}
{"title":"Microbubbles activated by low-frequency ultrasound enhance the anti-tumor effects of curcumin in glioma cells by suppressing the TGF-β1/Smad/VEGF/NCAM signaling pathway.","authors":"Lixia Mei, Zhen Zhang, Xiaole Song, Xiaodi Zhao","doi":"10.4149/gpb_2023024","DOIUrl":"10.4149/gpb_2023024","url":null,"abstract":"<p><p>This study investigated whether microbubbles activated by low-frequency ultrasound enhanced the anti-tumor effects of curcumin in glioma cells. CCK8 proliferation assay, scratch migration assay, and transwell invasion assay were performed to estimate the proliferation, migration, and invasion rates of the glioma cells in blank control and different treatment groups, respectively. Quantitative RT-PCR (qRT-PCR) analysis was performed to determine the relative expression levels of VEGF and NCAM mRNAs in the various experimental groups. Western blotting was performed to determine the activity status of the TGF-β1/Smad signaling pathway in various groups of glioma cells by estimating the expression levels of p-SMAD2/3, VEGF, and NCAM proteins. Combined treatment (Cur-Us-MBs) with microbubbles activated by low-frequency ultrasound and curcumin significantly reduced the in vitro proliferation, migration, and invasiveness of glioma cells compared to the control and other treatment groups. Furthermore, Cur-Us-MBs significantly reduced the expression levels of VEGF and NCAM mRNAs and proteins and p-Smad2/3 proteins , including those cells stimulated with rhTGF-β. These suggested that microbubbles activated by low-frequency ultrasound enhanced the inhibition of TGF-β1/Smad/VEGF/NCAM signaling pathway by curcumin,and enhanced the antitumor effects of curcumin by significantly reducing in vitro proliferation, migration, and invasiveness of glioma cells through this pathway.</p>","PeriodicalId":12514,"journal":{"name":"General physiology and biophysics","volume":"43 1","pages":"73-84"},"PeriodicalIF":1.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139680988","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}
{"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":"43 1","pages":"13-23"},"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":" ","pages":"469-478"},"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":"42 5","pages":"387-401"},"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":"42 5","pages":"431-442"},"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":"42 5","pages":"457-468"},"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":"42 5","pages":"403-415"},"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}