Andrii Sydorchuk, Larysa Sydorchuk, Adelina Gutnitska, Valentina Vasyuk, Oleksii Tkachuk, Valentina Dzhuryak, Yuriy Myshkovskii, Petro Kyfiak, Ruslan Sydorchuk, Oksana Iftoda
{"title":"The role of NOS3 (rs2070744) and GNB3 (rs5443) genes' polymorphisms in endothelial dysfunction pathway and carotid intima-media thickness in hypertensive patients.","authors":"Andrii Sydorchuk, Larysa Sydorchuk, Adelina Gutnitska, Valentina Vasyuk, Oleksii Tkachuk, Valentina Dzhuryak, Yuriy Myshkovskii, Petro Kyfiak, Ruslan Sydorchuk, Oksana Iftoda","doi":"10.4149/gpb_2022060","DOIUrl":"https://doi.org/10.4149/gpb_2022060","url":null,"abstract":"<p><p>The mechanisms orchestrating the balance between nitric oxide and endothelium-derived contracting factors, and genetic predisposition to endothelial dysfunction in hypertensive patients remain to be determined. One-hundred hypertensive patients participated in the case-control study to clarify the risk of endothelial dysfunction and carotid \"intima media\" thickness (IMT) changes depending on NOS3 (rs2070744) and GNB3 (rs5443) genes' polymorphisms. It is found that presence of NOS3 gene's С-allele significantly elevates the risk of atherosclerotic plaques on carotid arteries (OR95%CI: 1.24-11.20; р = 0.019) and the probability of low NOS3 gene expression (OR95%CI: 17.72-520.0; р < 0.001). Homozygous carriage of С-allele of GNB3 gene is protective and corresponds to the lowest chances of the carotid IMT increase, atherosclerotic plaques formation and sVCAM-1 elevation (OR = 0.10-0.34; OR95%CI: 0.03-0.95; р ≤ 0.035-0.001). Vice versa, Т-allele of GNB3 gene significantly augments the risk of the carotid IMT increase (OR95%CI: 1.09-7.74; р = 0.027) including development of atherosclerotic plaques, associating GNB3 (rs5443) with cardiovascular pathology.</p>","PeriodicalId":12514,"journal":{"name":"General physiology and biophysics","volume":"42 2","pages":"179-190"},"PeriodicalIF":1.5,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9089301","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":"Protective effects of NF-κB inhibitor and continuous perfusion of pulmonary arteries on pulmonary injury in piglet models of deep hypothermia low flow.","authors":"Yewei Xie, Rufang Zhang, Jia Li","doi":"10.4149/gpb_2022058","DOIUrl":"https://doi.org/10.4149/gpb_2022058","url":null,"abstract":"<p><p>Deep hypothermia with low flow perfusion (DHLF) is a common cardiopulmonary bypass (CPB) technique. The associated lung ischemia/reperfusion injury is a major cause of postoperative morbidity and mortality in patients undergoing DHLP; we aimed to investigate the effects of nuclear factor-κB (NF-κB) inhibitor pyrrolidine dithiocarbamate (PDTC) with continuous perfusion of pulmonary arteries (CPP) on DHLF-induced lung injury and the related molecular mechanisms. Twenty-four piglets were randomly divided into the DHLF (control), CPP (with DHLF), or CPP+PDTC (intravenous PDTC before CPP with DHLF) groups. Lung injury was evaluated by respiratory function measurement, lung immunohistochemistry, and serum levels of TNF, IL-8, IL-6, and NF-κB before CPB, at CPB completion, and at 1 h post-CPB. Western blot was used to detect NF-κB protein expression in lung tissues. After CPB, decreased parcial pressure of oxygen (PaO2) and increased parcial pressure of carbon dioxide (PaCO2) and serum levels of TNF, IL-8, IL-6, and NF-κB were observed in the DHLF group. Both CPP and CPP+PDTC groups showed better indices of lung function, decreased levels of TNF, IL-8, and IL-6, and less severe pulmonary edemas and injuries. PDTC with CPP further improved pulmonary function and mitigated pulmonary injury than did CPP alone. PDTC with CPP better attenuates DHLF-induced lung injury than does CPP alone.</p>","PeriodicalId":12514,"journal":{"name":"General physiology and biophysics","volume":"42 2","pages":"169-177"},"PeriodicalIF":1.5,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9152582","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":"Stress, depression, and hippocampus: from biochemistry to electrophysiology.","authors":"Alzbeta Idunkova, Lubica Lacinova, Lucia Dubiel-Hoppanova","doi":"10.4149/gpb_2023001","DOIUrl":"https://doi.org/10.4149/gpb_2023001","url":null,"abstract":"<p><p>Major depressive disorder is a very common serious mental illness with increasing prevalence in the population. Its pathology includes biochemical, morphological, and electrophysiological changes in various brain areas. In spite of decades of extensive research pathophysiology of depression is still not sufficiently understood. When depression occurs just before or during pregnancy, it may have a detrimental effect on perinatal and/or postnatal brain development, affecting the offspring's behavior. An important role in the pathology of depression is the hippocampus as a center for cognition and memory. Here we review changes in morphology, biochemical, and electrical signaling caused by depression in first and second generation identified in various animal models.</p>","PeriodicalId":12514,"journal":{"name":"General physiology and biophysics","volume":"42 2","pages":"107-122"},"PeriodicalIF":1.5,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9089302","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":"Silencing of long non-coding RNA SOX2-overlapping transcript relieves myocardial ischemia/reperfusion injury through up-regulating miRNA-146a-5p.","authors":"Zhongxin Li, Guangdong Liu, Hua Huang","doi":"10.4149/gpb_2022065","DOIUrl":"https://doi.org/10.4149/gpb_2022065","url":null,"abstract":"<p><p>Long non-coding RNAs (lncRNAs) are involved in the development of myocardial ischemia/reperfusion injury (MIRI). In this study, we aimed to explore the regulatory effect and mechanism of lncRNA SOX2-overlapping transcript (SOX2-OT) in MIRI. The viability of oxygen and glucose deprivation/reperfusion (OGD/R)-treated H9c2 cells was detected by MTT assay. The levels of interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, malondialdehyde (MDA), and superoxide dismutase (SOD) were measured by ELISA. The target relationship between SOX2-OT and miR-146a-5p was predicted by LncBase, and subsequently confirmed by Dual luciferase reporter assay. The effects of SOX2-OT silencing on myocardial apoptosis and function were further validated in MIRI rats. The expression of SOX2-OT was increased in OGD/R-treated H9c2 cells and myocardial tissues of MIRI rats. Silencing of SOX2-OT increased the viability and inhibited the inflammation and oxidative stress of OGD/R-treated H9c2 cells. SOX2-OT negatively regulated its target miR-146a-5p. Silencing of miR-146a-5p reversed the effects of sh-SOX2-OT on OGD/R-treated H9c2 cells. In addition, silencing of SOX2-OT also alleviated myocardial apoptosis and improved myocardial function in MIRI rats. Silencing of SOX2-OT relieved the apoptosis, inflammation, and oxidative stress of myocardial cells via up-regulating miR-146a-5p, contributing to the remission of MIRI.</p>","PeriodicalId":12514,"journal":{"name":"General physiology and biophysics","volume":"42 2","pages":"191-199"},"PeriodicalIF":1.5,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9089303","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":"Construction of a novel lncRNA-miRNA-mRNA competing endogenous RNA network in muscle in response to exercise training.","authors":"Mingkun Nie, Qingling Liu, Cheng Yan","doi":"10.4149/gpb_2022062","DOIUrl":"https://doi.org/10.4149/gpb_2022062","url":null,"abstract":"<p><p>Physical inactivity has evidently been a hazard factor for many diseases, including cardiovascular disease, diabetes, cancer, etc. Rising evidence indicates that RNA, as competitive endogenous RNA (ceRNA), plays an important role in adaptive changes in skeletal muscle in response to exercise training. Although the effects of exercise-induced fitness on skeletal muscle have been well established, the mechanisms underlying are not fully understood. The purpose of this study is to construct a novel ceRNA network in skeletal muscle in response to exercise training. Skeletal muscle gene expression profiles were downloaded from the GEO database. Then, we identified differentially expressed lncRNAs, miRNAs, and mRNAs between the pre-exercise and post-exercise samples. Subsequently, we constructed lncRNA-miRNA-mRNA regulatory networks based on the ceRNA theory. 1153 mRNAs (687 upregulated and 466 downregulated), 7 miRNAs (3 upregulated and 4 downregulated), and 5 lncRNAs (3 upregulated and 2 downregulated) were identified as differentially expressed genes. 3 lncRNAs, 5 miRNAs and 227 mRNAs were obtained to build miRNA-mediated ceRNA networks. We constructed a novel ceRNA regulatory network in muscle in response to exercise training, which provides insights into molecular mechanisms underlying the health benefits brought by physical activity.</p>","PeriodicalId":12514,"journal":{"name":"General physiology and biophysics","volume":"42 2","pages":"123-133"},"PeriodicalIF":1.5,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9089300","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}
Tomas Baka, Peter Stanko, Kristina Repova, Silvia Aziriova, Kristina Krajcirovicova, Andrej Barta, Stefan Zorad, Fedor Simko
{"title":"Ivabradine curbs isoproterenol-induced kidney fibrosis.","authors":"Tomas Baka, Peter Stanko, Kristina Repova, Silvia Aziriova, Kristina Krajcirovicova, Andrej Barta, Stefan Zorad, Fedor Simko","doi":"10.4149/gpb_2022057","DOIUrl":"https://doi.org/10.4149/gpb_2022057","url":null,"abstract":"<p><p>This study investigated whether chronic isoproterenol administration could induce kidney alterations and whether ivabradine, a heart rate (HR)-reducing substance exerting cardiovascular protection, is able to attenuate potential kidney damage. Twenty-eight Wistar rats were divided into non-diseased controls, rats treated with ivabradine, rats treated with isoproterenol, and rats treated with isoproterenol plus ivabradine. Six weeks of isoproterenol administration was associated with decreased systolic blood pressure (SBP) (by 25%) and glomerular, tubulointerstitial and vascular/perivascular fibrosis due to enhanced type I collagen volume (7-, 8-, and 4-fold, respectively). Ivabradine reduced HR (by 15%), partly prevented SBP decline (by 10%) and site-specifically mitigated kidney fibrosis by decreasing type I collagen volume in all three sites investigated (by 69, 58, and 67%, respectively) and the ratio of type I collagen-to-type III collagen in glomerular and vascular/perivascular sites (by 79 and 73%, respectively). We conclude that ivabradine exerts protection against kidney remodelling in isoproterenol-induced kidney damage.</p>","PeriodicalId":12514,"journal":{"name":"General physiology and biophysics","volume":"42 2","pages":"209-215"},"PeriodicalIF":1.5,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9458852","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}
Alparslan Koç, Mustafa Gazi, Ali Caner Sayar, Didem Onk, Muhammet Ali Arı, Bahadır Süleyman, Ahmet Gökhan Ağgül, Fikret Altındağ, Durdu Altuner, Halis Süleyman
{"title":"Molecular mechanism of the protective effect of adenosine triphosphate against paracetamol-induced liver toxicity in rats.","authors":"Alparslan Koç, Mustafa Gazi, Ali Caner Sayar, Didem Onk, Muhammet Ali Arı, Bahadır Süleyman, Ahmet Gökhan Ağgül, Fikret Altındağ, Durdu Altuner, Halis Süleyman","doi":"10.4149/gpb_2022055","DOIUrl":"https://doi.org/10.4149/gpb_2022055","url":null,"abstract":"<p><p>Toxic doses of paracetamol are also known to be close to therapeutic doses. This study aimed to biochemically investigate the protective effect of ATP against paracetamol-induced oxidative liver injury in rats and to examine the tissues histopathologically. We divided the animals into the paracetamol alone (PCT), ATP + paracetamol (PATP), and healthy control (HG) groups. Liver tissues were examined biochemically and histopathologically. Malondialdehyde level, AST and ALT activity in the PCT group were significantly higher than those in the HG and PATP groups (p < 0.001). The glutathione (tGSH) level, superoxide dismutase (SOD) and catalase (CAT) activity in the PCT group was significantly lower than that in the HG and PATP groups (p < 0.001), while animal SOD activity was significantly different between the PATP and HG groups (p < 0.001). The activity of CAT was almost the same. In the group treated with paracetamol alone, lipid deposition, necrosis, fibrosis, and grade 3 hydropic degeneration were observed. No histopathological damage was observed of the ATP-treated group, except for grade 2 edema. We discovered that ATP reduces the oxidative stress caused by paracetamol ingestion and protects against paracetamol-induced liver injury at the macroscopic and histological levels.</p>","PeriodicalId":12514,"journal":{"name":"General physiology and biophysics","volume":"42 2","pages":"201-208"},"PeriodicalIF":1.5,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9458853","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}
Elshymaa A Abdel-Hakeem, Nagwa M Zenhom, Sahar A Mokhemer
{"title":"Testicular cytoprotective effect of glucagon like peptide-1 in diabetic rats involves inhibition of apoptosis, endoplasmic reticulum stress and activation of autophagy.","authors":"Elshymaa A Abdel-Hakeem, Nagwa M Zenhom, Sahar A Mokhemer","doi":"10.4149/gpb_2022064","DOIUrl":"https://doi.org/10.4149/gpb_2022064","url":null,"abstract":"<p><p>This study aimed to explore the possible cytoprotective effects of exenatide, a glucagon-like peptide-1 (GLP-1) receptor agonist, in the testicles of diabetic rats. Exenatide has numerous advantageous properties in addition to its hypoglycemic effect. However, its impact on testicular tissue in diabetes needs more clarification. Therefore, rats were divided into control, exenatide-treated, diabetic and exenatide-treated diabetic groups. Blood glucose and serum levels of insulin, testosterone, pituitary gonadotropins and kisspeptin-1 were measured. Real-time PCR for beclin-1, p62, mammalian target of rapamycin (mTOR), and AMP-activated protein kinase (AMPK), were estimated in testicular tissue in addition to markers of oxidative stress, inflammation, and endoplasmic reticulum stress. Also, immuno-expression of protein P53, nuclear erythroid factor2 (Nrf2) and vimentin was conducted. Exenatide was able to attenuate diabetic toxic changes and enhance autophagy in testicular tissue. These results indicate the protective effect of exenatide against diabetic testicular dysfunction.</p>","PeriodicalId":12514,"journal":{"name":"General physiology and biophysics","volume":"42 2","pages":"135-148"},"PeriodicalIF":1.5,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10311818","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":"Circ_0001498 contributes to lipopolysaccharide-induced lung cell apoptosis and inflammation in sepsis-related acute lung injury via upregulating SOX6 by interacting with miR-574-5p.","authors":"Wei Hu, Qin Wang, Zhichun Luo, Yaqiong Shi, Liangping Zhang, Zhijun Zhang, Jianlin Liu, Kelan Liu","doi":"10.4149/gpb_2022054","DOIUrl":"https://doi.org/10.4149/gpb_2022054","url":null,"abstract":"<p><p>Circular RNAs (circRNAs) have important regulation in in sepsis-related acute lung injury (ALI). Circ_0001498 was significantly overexpressed in sepsis-induced acute respiratory distress syndrome. The aims of this study were to explore role and mechanism of circ_0001498 in lipopolysaccharide (LPS)-treated WI-38 cells. Human samples were collected from 56 sepsis patients and 46 healthy volunteers at Liyang People's Hospital. Circ_0001498, microRNA-574-5p (miR-574-5p) or sex-determining region Y-related high-mobility-group box 6 (SOX6) levels were detected via reverse transcription-quantitative polymerase chain reaction assay. Cell viability was determined through Cell Counting Kit-8 assay. Apoptosis rate was examined by flow cytometry. Western blot was used for measurement of proteins. Inflammatory cytokines were detected via enzyme-linked immunosorbent assay. Target relation was analyzed via dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. Circ_0001498 was overexpressed in sepsisrelated ALI patients and LPS-treated WI-38 cells. Silencing circ_0001498 reduced LPS-induced cell apoptosis and inflammation. Circ_0001498 interacted with miR-574-5p. The regulation of circ_0001498 knockdown was abolished by miR-574-5p inhibitor. Furthermore, miR-574-5p directly targeted SOX6 and circ_0001498 upregulated SOX6 via targeting miR-574-5p. Overexpression of miR-574-5p alleviated LPS-induced cell injury by downregulating SOX6. This research identified that circ_0001498 facilitated sepsis-related ALI progression by targeting miR-574-5p to upregulate SOX6.</p>","PeriodicalId":12514,"journal":{"name":"General physiology and biophysics","volume":"42 1","pages":"37-47"},"PeriodicalIF":1.5,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10601774","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}
Maria Komelkova, Boris Yushkov, Stanislav Fedorov, Roman Ibragimov, Pavel Platkovskiy, Desheng Hu, Shanshan Luo, Alexey Sarapultsev
{"title":"Early-life maternal deprivation in rats increases sensitivity to the subsequent stressors: a pilot study","authors":"Maria Komelkova, Boris Yushkov, Stanislav Fedorov, Roman Ibragimov, Pavel Platkovskiy, Desheng Hu, Shanshan Luo, Alexey Sarapultsev","doi":"10.4149/gpb_2023022","DOIUrl":"https://doi.org/10.4149/gpb_2023022","url":null,"abstract":"Early life experiences, particularly maternal deprivation (MD), have long-lasting implications on emotional and cognitive development. Using Wistar rats as a model, this study explores the impact of MD followed by predator stress exposure (PSS) to simulate aspects of post-traumatic stress disorder (PTSD). A cohort of 41 male rat pups underwent MD from postnatal days 2 to 14, followed by PSS at day 90. Female rat pups were not included in the experiment. Behavior was subsequently assessed using the Elevated Plus Maze test 14 days post-PSS. While MD led to subtle changes such as decreased activity and increased anxiety-like behavior, PSS induced pronounced anxiogenic effects. Notably, PSS after MD resulted in decreased basal corticosterone levels, mirroring conditions observed in PTSD. The findings suggest that although MD itself does not induce significant behavioral changes, it predisposes individuals to heightened sensitivity to subsequent stressors. This study underscores the utility of a two-stage PSS model for more accurately reflecting the complexities inherent in stress-related disorders, including PTSD.","PeriodicalId":12514,"journal":{"name":"General physiology and biophysics","volume":"14 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135704116","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}