Chinese Journal of Physiology最新文献

{"title":"Ophiopogonin D improves oxidative stress and mitochondrial dysfunction in pancreatic β cells induced by hydrogen peroxide through Keap1/Nrf2/ARE pathway in diabetes mellitus.","authors":"Hongyan Zhang, Xuezhi Kang, Jun Ruan, Li Ma, Wenbo Peng, Haonan Shang, Bing Wang, Yongning Sun","doi":"10.4103/cjop.CJOP-D-23-00069","DOIUrl":"10.4103/cjop.CJOP-D-23-00069","url":null,"abstract":"<p><p>Diabetes mellitus (DM) is a metabolic disease characterized by high blood sugar. Due to its complex pathogenesis, no effective drugs have been found so far. Ophiopogonin D (OP-D) has anti-inflammatory, antioxidant, and anticancer activities, but its role in DM has not been studied so far. Hydrogen peroxide (H₂O₂) was used to induce INS-1 cells. INS-1 cells induced by H₂O₂ were treated with OP-D, and cell apoptosis, oxidative stress damage, and related indexes of mitochondrial function were respectively detected by cell counting kit-8, flow cytometry, western blot, enzyme-linked immunosorbent assay, real-time quantitative polymerase chain reaction, JC-1 fluorescent probe, and related kits. Subsequently, molecular docking techniques were used to investigate the relationship between OP-D and Keap1 and to explore the regulation mechanism of OP-D on H₂O₂-induced oxidative stress and mitochondrial function in INS-1 cells. OP-D inhibited the apoptosis and oxidative stress level of H₂O₂-induced INS-1 cells, thereby inhibiting cell damage. Moreover, OP-D inhibited mitochondrial dysfunction in H₂O₂-induced INS-1 cells. At last, we found that Keap1/Nrf2 specific signaling pathway inhibitor ML385 was able to reverse the inhibitory effect of OP-D on H₂O₂-induced oxidative stress and mitochondrial dysfunction in INS-1 cells. In conclusion, OP-D improves oxidative stress and mitochondrial dysfunction in pancreatic β cells induced by H₂O₂ through activating Keap1/Nrf2/ARE pathway in DM.</p>","PeriodicalId":10251,"journal":{"name":"Chinese Journal of Physiology","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139039578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effect of long-term moderate exercise on myocardial metabolome in rats.","authors":"Zheng Ping, Xiao Li Zhang, Zi Wen Wang, Xue Bin Cao","doi":"10.4103/cjop.CJOP-D-23-00126","DOIUrl":"10.4103/cjop.CJOP-D-23-00126","url":null,"abstract":"<p><p>Regular moderate physical exercise is beneficial for the cardiovascular system. Our prior study has demonstrated a long-term moderate exercise (4-week of 60-min 74.0% V̇O_2max treadmill running) is optimal in protecting from exhaustive exercise-induced cardiac ischemic injury. This study is aimed to investigate the effect of long-term moderate exercise on myocardial metabolome in rats. Thirteen male Sprague-Dawley rats were randomly assigned into the control group (C) and the long-term moderate exercise group (E). The targeted metabolomics of the myocardium was analyzed by ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) system. Results showed that the metabolites categories of bile acids (BAs), fatty acids (FAs), and phenylpropanoic acids were significantly decreased. The biosynthesis of unsaturated FAs pathway was significantly downregulated. The altered metabolites in the E Group included decreased FAs (pentadecanoic acid, 10Z-heptadecenoic acid, dihomo-gamma-linolenic acid, docosahexaenoic acid, docosapentaenoic acid, and 10Z-nonadecenoic acid), decreased BAs (chenodeoxycholic acid and beta-muricholic acid), decreased organic acids (glycolic acid and 2-hydroxyglutaric acid), decreased carbohydrate (N-acetylneuraminic acid, Neu5Ac), decreased amino acids (α-aminobutyric acid and norvaline), decreased phenylpropanoic acids (hydroxyphenyllactic acid), and benzoic acids (4-hydroxybenzoic acid and phthalic acid). The results indicated that long-term moderate exercise has promoted lipids utilization in myocardium while exerted little influence on carbohydrate metabolism and diminished many detrimental metabolites. Notably, decrease of myocardial carbohydrate Neu5Ac after long-term moderate exercise might predict a prospective metabolomics biomarker for cardioprotection. This research has displayed the effect of long-term moderate exercise on myocardial metabolomic profiling in rats and indicated some promising metabolites which can be applied for exercise benefits in future.</p>","PeriodicalId":10251,"journal":{"name":"Chinese Journal of Physiology","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139039581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sevoflurane attenuates proliferative and migratory activity of lung cancer cells via mediating the microRNA-100-3p/sterol O-Acyltransferase 1 axis.","authors":"Bicheng Fu, Fucheng Zhou, Jian Zhang, Xianglong Kong, Boxiong Ni, Jianlong Bu, Shidong Xu, Changjun He","doi":"10.4103/cjop.CJOP-D-22-00124","DOIUrl":"10.4103/cjop.CJOP-D-22-00124","url":null,"abstract":"<p><p>Recently, evidence has shown that microRNA-100-3p (miR-100-3p) has been revealed as a tumor suppressor in diverse human diseases, while its capability in lung cancer warrants further validation. In this work, we aimed to discuss the impact of sevoflurane on biological functions of lung cancer cells by modulating the miR-100-3p/sterol O-acyltransferase 1 (SOAT1) axis. Lung cancer cell lines (A549 and H460) were treated with various concentrations of sevoflurane. Cell viability, proliferation, migration, and invasion were evaluated using MTT, colony formation, wound healing, and transwell assays. Moreover, miR-100-3p and SOAT1 expressions were evaluated by reverse transcription-quantitative polymerase chain reaction in lung cancer cells. The target interaction between miR-100-3p and SOAT1 was predicted by bioinformatics analysis and verified by the dual-luciferase reporter gene assay. The findings of our work demonstrated that sevoflurane impeded the abilities on viability, proliferation, migration, and invasion of A549 and H460 cells. The expression of miR-100-3p was reduced, and SOAT1 expression was elevated in lung cancer cells. miR-100-3p targeted SOAT1. Besides, sevoflurane could lead to expressed improvement of miR-100-3p or limitation of SOAT1. Downregulation of miR-100-3p or upregulation of SOAT1 restored the suppression of sevoflurane on abilities of viability, proliferation, migration, and invasion in A549 and H460 cells. In the rescue experiment, downregulation of SOAT1 reversed the impacts of downregulation of miR-100-3p on sevoflurane on lung cancer cells. Collectively, our study provides evidence that sevoflurane restrained the proliferation and invasion in lung cancer cells by modulating the miR-100-3p/SOAT1 axis. This article provides a new idea for further study of the pathogenesis of lung cancer.</p>","PeriodicalId":10251,"journal":{"name":"Chinese Journal of Physiology","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139039580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Icariside II suppresses ferroptosis to protect against MPP⁺-Induced Parkinson's disease through Keap1/Nrf2/GPX4 signaling.","authors":"Wenbo Fan, Jianwu Zhou","doi":"10.4103/cjop.CJOP-D-23-00107","DOIUrl":"10.4103/cjop.CJOP-D-23-00107","url":null,"abstract":"<p><p>Parkinson's disease (PD) is recognized as a degenerative and debilitating neurodegenerative disorder. The novel protective role of icariside II (ICS II) as a plant-derived flavonoid compound in neurodegenerative diseases has aroused much attention. Herein, the definite impacts of ICS II on the process of PD and the relevant action mechanism were studied. Human neuroblastoma SK-N-SH cells were challenged with 1-methyl-4-phenylpyridinium ion (MPP⁺) to construct the PD cell model. MTT assay and flow cytometry analysis, respectively, appraised cell viability and apoptosis. Caspase 3 Activity Assay examined caspase 3 activity. Corresponding kits examined oxidative stress levels. BODIPY 581/591 C11 assay evaluated lipid reactive oxygen species. Iron Assay Kit assessed iron content. Western blot tested the expression of apoptosis-, ferroptosis- and Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2)/glutathione peroxidase 4 (GPX4) signaling-associated proteins. Molecular docking verified the binding of ICS II with Keap1. The existing experimental results unveiled that ICS II elevated the viability whereas reduced the apoptosis, oxidative stress, and ferroptosis in MPP⁺-treated SK-N-SH cells in a concentration-dependent manner. Furthermore, ICS II declined Keap1 expression while raised Nrf2, heme oxygenase 1, and GPX4 expression. In addition, ICS II had a strong binding with Keap1 and Nrf2 inhibitor ML385 partially abolished the suppressive role of ICS II in MPP⁺-triggered apoptosis, oxidative stress, and ferroptosis in SK-N-SH cells. To summarize, ICS II might inhibit apoptosis, oxidative stress, and ferroptosis in the MPP⁺-stimulated PD cell model, which might be due to the activation of Keap1/Nrf2/GPX4 signaling.</p>","PeriodicalId":10251,"journal":{"name":"Chinese Journal of Physiology","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139039574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Irbesartan eases lipopolysaccharide-induced lung injury <i>In Vitro</i> and <i>In Vivo</i>.","authors":"Zhongyuan Zhang, Wei Wang","doi":"10.4103/cjop.CJOP-D-23-00131","DOIUrl":"10.4103/cjop.CJOP-D-23-00131","url":null,"abstract":"<p><p>Acute lung injury (ALI) is classified as a devastating pulmonary disorder contributing to significant incidence and fatality rate. Irbesartan (IRB) is an angiotensin II receptor blocker that has been proposed to protect against oleic acid-induced ALI. To this end, the current study is concentrated on ascertaining the role of IRB in ALI and figuring out the probable action mechanism. First, cell counting kit-8 (CCK-8) appraised the viability of human pulmonary microvascular endothelial cells (HPMVECs) exposed to ascending concentrations of IRB. HPMVEC injury model and a mouse model of ALI induced by lipopolysaccharide (LPS) were pretreated by IRB. In vitro, cell viability was estimated by CCK-8 assay, and lactate dehydrogenase (LDH) release was tested by LDH assay kit. Enzyme-linked immunosorbent assay (ELISA) and Western blotting estimated the expression levels of inflammatory factors. Fluorescein isothiocyanate-dextran was used to assess HPMVEC permeability. Western blotting examined the expression of adherent and tight junction proteins. In vivo, hematoxylin and eosin staining evaluated lung tissue damage and lung wet/dry (W/D) weight was measured. ELISA analyzed the levels of inflammatory factors in the serum and bronchoalveolar lavage fluid (BALF), and Western blotting examined the expression of inflammatory factors. The total cell, neutrophil, and macrophage numbers in BALF were determined using a cell counter. Lung capillary permeability was assayed by Evans blue albumin and total protein concentration in BALF was measured using bicinchoninic acid method. Immunofluorescence assay and Western blotting examined the expression of adherent and tight junction proteins in lung tissues. It was observed that IRB dose-dependently enhanced the viability while reduced LDH release, inflammatory response as well as permeability in LPS-challenged HPMVECs in vitro. In addition, LPS-stimulated lung tissue damage, pulmonary edema, inflammatory response as well as lung capillary permeability in vivo were all reversed following IRB treatment. Collectively, IRB treatment might elicit protective behaviors against LPS-triggered ALI.</p>","PeriodicalId":10251,"journal":{"name":"Chinese Journal of Physiology","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139039576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SPAG5 promotes the proliferation, migration, invasion, and epithelial-mesenchymal transformation of colorectal cancer cells by activating the PI3K/AKT signaling pathway.","authors":"Xuelian Zhang,&nbsp;Weiyu Wu,&nbsp;Xiaohui Li,&nbsp;Feng He,&nbsp;Lei Zhang","doi":"10.4103/cjop.CJOP-D-22-00165","DOIUrl":"10.4103/cjop.CJOP-D-22-00165","url":null,"abstract":"<p><p>Colorectal cancer (CRC) is a cancer that occurs in the rectum or colon with a high incidence. Sperm-associated antigen 5 (SPAG5), a gene that regulates cell division, has been observed highly expressed in a variety of cancers, but its role in CRC is unclear. This study aimed to investigate the regulatory role of SPAG5 in CRC. The expression of SPAG5 in multiple cancers and normal tissues was predicted by The Cancer Genome Atlas and Tumor Immune Estimation Resource, and the expression of SPAG5 in human normal intestinal epithelial cells NCM460 and human CRC cell lines Caco2, HT29, SW480, and LOVO was verified by western blotting (WB). The effects of silencing SPAG5 on cell viability, proliferation, and apoptosis were then investigated by cell counting kit-8, WB, and flow cytometry. The effects of silencing SPAG5 on cell migration and invasion were investigated by scratch assay and transwell assay. Finally, the phosphorylation levels of phosphoinositide 3-kinase (PI3K) and AKT in cells were detected by WB. The results showed that SPAG5 was highly expressed in CRC and was verified by WB. Silencing of SPAG5 inhibited cell viability and proliferation and increased the cell apoptosis rate. Furthermore, both cell invasion and migration abilities were suppressed by the low expression of SPAG5. Finally, WB results found that the phosphorylation levels of PI3K and AKT were reduced after SPAG5 silencing. In summary, the results showed that SPAG5 can promote the proliferation and invasion of CRC cells by targeting the PI3K/AKT signaling pathway.</p>","PeriodicalId":10251,"journal":{"name":"Chinese Journal of Physiology","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70707286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Klotho inhibits the activation of NLRP3 inflammasome to alleviate lipopolysaccharide-induced inflammatory injury in A549 cells and restore mitochondrial function through SIRT1/Nrf2 signaling pathway.","authors":"Yanjun Zeng, Gang Xu, Congrui Feng, Danyan Cai, Sizhi Wu, Yuanling Liu, Yuluo Chen, Wei Ma","doi":"10.4103/cjop.CJOP-D-23-00029","DOIUrl":"10.4103/cjop.CJOP-D-23-00029","url":null,"abstract":"<p><p>Acute lung injury is a severe clinical condition constituting a major cause of mortality in intensive care units. This study aimed to investigate the role of klotho in alleviating lipopolysaccharide (LPS)-induced acute lung injury. LPS-induced acute lung injury was used to simulate the acute lung injury caused by severe pneumonia in vitro. The viability and apoptosis of A549 cells were detected by cell counting kit-8 assay and flow cytometry. The inflammatory response, oxidative stress, and mitochondrial function in A549 cells were analyzed by commercial assay kits and 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethyl-benzimidazolyl carbocyanine iodide (JC-1) staining. The expression of apoptosis-related proteins, Sirtuin 1 (SIRT1)/nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway-related proteins, and NOD-like receptor family pyrin domain containing 3 (NLRP3) expression in A549 cells was detected by western blot. The mtDNA synthase level in A549 cells was analyzed by reverse transcription-quantitative polymerase chain reaction. The results showed that, klotho had no cytotoxic effect on A549 cells. The viability and mitochondrial function were inhibited and apoptosis, inflammatory response, and oxidative stress were aggravated in LPS-induced A549 cells, which were all reversed by klotho. Klotho activated the SIRT1/Nrf2 signaling pathway to inhibit the LPS-induced NLRP3 inflammasome activation in A549 cells. However, EX527, a SIRT1 inhibitor, attenuated the klotho effect to suppress viability and mitochondrial function and promoted apoptosis, inflammatory response, and oxidative stress of A549 cells. In conclusion, klotho inhibited the activation of NLRP3 inflammasome to alleviate LPS-induced inflammatory injury of A549 cells and restore mitochondrial function through activating the SIRT1/Nrf2 signaling pathway.</p>","PeriodicalId":10251,"journal":{"name":"Chinese Journal of Physiology","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70707478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correlation between serum beta-human chorionic gonadotropin levels and thyroid metabolic function in pregnant women with hyperemesis gravidarum.","authors":"Haiyan Zheng,&nbsp;Qian Wang,&nbsp;Feng Chen","doi":"10.4103/cjop.CJOP-D-23-00045","DOIUrl":"https://doi.org/10.4103/cjop.CJOP-D-23-00045","url":null,"abstract":"<p><p>As previously demonstrated, serum beta-human chorionic gonadotropin (β-hCG) is linked to identifying early gestational abnormalities. This research was aimed at investigating the correlation between serum β-hCG levels and thyroid metabolic function in pregnant women with hyperemesis gravidarum (HG). Ninety-one pregnant women with HG were selected as the study group and divided into early pregnancy (EP), mid-pregnancy (MP), and late pregnancy (LP) groups according to their gestational weeks, while 84 normal pregnant women were selected as the control group. Venous blood was collected from pregnant women in both groups and serum β-hCG levels were measured by chemiluminescent immunoassay. The levels of free thyroxine (FT4), free triiodothyronine (FT3), thyroid-stimulating hormone (TSH), thyroid peroxidase antibody (TPOAb), thyroid-stimulating hormone receptor antibody (TRAb), and thyroglobulin antibody (TgAb) were tested by chemiluminescent microparticle immunoassay. Visual analog scale (VAS) scores were utilized to assess the degree of HG. Pearson analysis was implemented to measure the correlations between serum β-hCG levels and serum FT3, FT4, TSH, TPOAb, TRAb, TgAb, as well as VAS scores and the correlations between β-hCG, FT3, FT4, TSH, TPOAb, TRAb, TgAb, as well as VAS scores and gestation period. The receiver operating characteristic (ROC) curve was plotted to analyze the diagnostic values of thyroid hormones, thyroid-related antibodies, and β-hCG levels for HG. Versus those in the control group, β-hCG, FT3, FT4, TPOAb, TRAb, TgAb levels, and VAS scores were higher and TSH levels were lower in the study group. Versus those in the EP group, β-hCG, FT3, FT4, TPOAb, TRAb, TgAb levels, and VAS scores of pregnant women in the MP and LP groups were decreased, and TSH levels were increased. Serum β-hCG levels of pregnant women with HG were positively correlated with FT3, FT4, TPOAb, TRAb, TgAb, and VAS scores and negatively correlated with TSH levels. Serum β-hCG, FT3, FT4, TPOAb, TRAb, TgAb levels, and VAS scores of pregnant women with HG had a negative correlation with the gestation period, while TSH levels had a positive correlation with the gestation period. The ROC curve analysis showed that β-hCG and thyroid function-related indicators were of high clinical values in the diagnosis of HG. Collectively, our article suggests that serum β-hCG expression of pregnant women with HG is abnormally elevated and closely related to the degree of HG and hyperthyroidism. In addition, β-hCG and thyroid function-related indicators have certain diagnostic efficacy for HG.</p>","PeriodicalId":10251,"journal":{"name":"Chinese Journal of Physiology","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71478665","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reducing myocardial infarction by combination of irisin and <i>Dendrobium nobile</i> Lindl through inhibiting nod-like receptor protein-3-related pyroptosis and activating PINK1/Parkin-mitophagy during aging.","authors":"Chen Ding, Chaofeng Zhang","doi":"10.4103/cjop.CJOP-D-23-00032","DOIUrl":"10.4103/cjop.CJOP-D-23-00032","url":null,"abstract":"<p><p>Aging, a crucial risk factor for ischemic heart disease, has negative impacts on cardioprotective mechanisms. As such, there is still an unmet requirement to explore potential therapies for improving the outcomes of myocardial ischemia/reperfusion (IR) injury in elderly subjects. Here, we aimed to confirm the cardioprotective function of irisin/Dendrobium nobile Lindl (DNL) combination therapy against myocardial IR injury in aged rats, with a focus on the involvement of pyroptosis and mitophagy. Male aged Wistar rats (22-24 months old, 400-450 g; n = 54) underwent myocardial IR or sham surgery. Before IR operation, rats were pretreated with irisin (0.5 mg/kg, intraperitoneally) and/or DNL (80 mg/kg, orally) for 1 or 4 weeks, respectively, at corresponding groups. Cardiac function, lactate dehydrogenase (LDH) and cardiac-specific isoform of troponin-I (cTn-I) levels, the expression of proteins involved in pyroptosis (nod-like receptor protein-3 (NLRP3), apoptosis-associated speck-like protein, c-caspase-1, and GSDMD-N) and mitophagy (PINK1 and Parkin), and pro-inflammatory cytokines levels were evaluated after 24 h of reperfusion. Irisin/DNL combined therapy significantly restored cardiac function and decreased LDH and cTn-I levels. It also downregulated pyroptosis-related proteins, upregulated PINK1 and Parkin, and decreased pro-inflammatory cytokines secretion. Pretreatment with Mdivi-1, as mitophagy inhibitor, abolished the cardioprotective action of dual therapy. This study revealed the cardioprotective effects of irisin/DNL combination therapy against IR-induced myocardial injury in aged rats, and also showed that the mechanism might be associated with suppression of NLRP3-related pyroptosis through enhancing the activity of the PINK1/Parkin mitophagy. This combination therapy is worthy of further detailed studies due to its potential to alleviate myocardial IR injury upon aging.</p>","PeriodicalId":10251,"journal":{"name":"Chinese Journal of Physiology","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71478670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PRPF19 promotes the proliferation, migration, and inhibits autophagy in prostate cancer by suppressing SLC40A1.","authors":"Guofei Zhang, Wansong Zhang, Mingjiang Dan, Feng Zou, Chunming Qiu, Canbiao Sun","doi":"10.4103/cjop.CJOP-D-22-00152","DOIUrl":"10.4103/cjop.CJOP-D-22-00152","url":null,"abstract":"<p><p>Prostate cancer (PCa) is a common cancer and the leading cause of cancer-related death in men. To investigate the role of pre-mRNA processing factor 19 (PRPF19) in proliferation, migration of PCa, and evaluate the potential ability of PRPF19 as a therapeutic target. PRPF19 expression was analyzed from The Cancer Genome Atlas and GEPIA databank. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to evaluate the transcription of PRPF9 and solute carrier family 40 member 1 (SLC40A1). Immunohistochemistry (IHC) was used to test PRPF9 expression in PCa tissues. The cell viability and 5-ethynyl-2'-deoxyuridine incorporation analysis were performed to assess cell proliferation. Transwell assay was performed to investigate the migration and invasion of cancer cells. Western blot was used to measure the expression level of PRPF9, E-cadherin, Vimentin and α-smooth muscle actin (α-SMA), SLC40A1, LC3, Beclin-1 and ATG7. Immunofluorescence assay was performed to measure LC3 expression in PCa cells. The bioinformatic analysis revealed PRPF19 was highly expressed in PCa which was certified by qRT-PCR, western blot and IHC detection in PCa tissues. The proliferation of PCa cells could be promoted by PRPF19 overexpression and suppressed by PRPF19 knockdown. Moreover, the migration and invasion of PCa cells could be positively regulated by PRPF19 which promoted the expression of E-cadherin, Vimentin, and α-SMA. Furthermore, the expression of LC3, Beclin-1, and ATG7 was negatively regulated by PRPF19, indicating that PRPF19 inhibited autophagy in PCa cells. In the double knockdown of PRPF19 and SLC40A1, PRPF19 repressed the mRNA and reduced protein level of SLC40A1, and SLC40A1 antagonized effects of PRPF19 on proliferation, migration and autophagy of PCa cells. PRPF19 promoted proliferation and migration, and inhibited autophagy in PCa by attenuating SLC40A1 expression, indicating PRPF19 was a potential therapeutic target for PCa treatment.</p>","PeriodicalId":10251,"journal":{"name":"Chinese Journal of Physiology","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70707139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}