Medical Science Monitor Basic Research最新文献

{"title":"The Effects of Progranulin in a Rat Model of Acute Myocardial Ischemia/Reperfusion are Mediated by Activation of the P13K/Akt Signaling Pathway","authors":"A. M. Alyahya, A. Al-Masri, A. Hersi, E. El Eter, S. Husain, R. Lateef, Ola H. Mawlana","doi":"10.12659/MSMBR.916258","DOIUrl":"https://doi.org/10.12659/MSMBR.916258","url":null,"abstract":"Background Progranulin is an adipokine, encoded by the progranulin (GRN) gene. Progranulin is expressed in atherosclerosis, but its effects in cardiac ischemia and reperfusion injury are unknown. Therefore, this study aimed to investigate the effects of progranulin in a rat model of acute myocardial ischemia/reperfusion (MI/R) injury in vivo. Material/Methods The model of acute MI/R injury was established in male Wistar rats by ligation of the left anterior descending (LAD) coronary artery for 30 minutes and reperfusion for 60 minutes. Before modeling, one group was treated with progranulin (0.03 μg/kg), and one group was treated with the P13K/Akt inhibitor, LY294002 (3 mg/kg). Left ventricular function (LV) was monitored, including the LV systolic pressure (LVSP), LV end-diastolic pressure (LVEDP), and changes in LV pressure. At the end of the study, blood and myocardial tissue were examined. Cardiac biochemical markers, histopathology, gene expression, and apoptosis were analyzed. Results Progranulin improved cardiac function following acute MI/R injury and significantly improved recovery of cardiac contractility and LVSP. Progranulin significantly reduced myocyte apoptosis, inflammation, and tissue edema, and was highly expressed in cardiac tissue following MI/R injury. The cardioprotective effect of progranulin was reduced by blocking the P13K/Akt signaling pathway. Conclusions In the rat model of acute MI/R injury, progranulin had a protective effect on cardiac function and morphology, associated with activation of the P13K/Akt signaling pathway. The mechanisms of the anti-apoptotic, anti-inflammatory, and inotropic effects of progranulin in the setting of acute MI/R injury require further in vivo studies.","PeriodicalId":18491,"journal":{"name":"Medical Science Monitor Basic Research","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2019-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88331100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exosome-Mediated MiR-155 Transfer Contributes to Hepatocellular Carcinoma Cell Proliferation by Targeting PTEN","authors":"Jing Sun, Dong Zhang, Cai-Jie Gao, Ye-wei Zhang, Q. Dai","doi":"10.12659/MSMBR.918134","DOIUrl":"https://doi.org/10.12659/MSMBR.918134","url":null,"abstract":"Background Most eukaryocytes release nano vesicles (30–120 nm), named exosomes, to various biological fluids such as blood, lymph, and milk. Hepatocellular carcinoma (HCC) is one of the tumors with the highest incidence rate in primary malignant carcinoma of the liver. However, the mechanism of HCC proliferation remains elusive. In this study, we aim to explore whether HCC cell-derived exosomes affect the proliferation of cancer cells. Material/Methods Exosomes were isolated from HCC cells by ultracentrifugation and were visualized the phenotype by transmission electron microscopy. Cell proliferation was detected by Cell Counting Kit-8 assays and EdU (5-ethynyl-2-deoxyuridine) incorporation assays. Dual-luciferase assays were performed to validate the paired correlation of miR-155 and 3′-UTR of PTEN (gene of phosphate and tension homology deleted on chromosome 10). A xenograft mice model was constructed to verify the effect of exosome-mediated miR-155 on cell proliferation in vivo. Results Our finding showed that miR-155 was enriched in exosomes released from HCC cells. The exosome-containing miR-155 transferred into new HCC targeted cells and lead to the elevation of HCC cells’ proliferation. Besides, the exosomal miR-155 directly bound to 3′-UTR of PTEN leading to the reduction of relevant targets in recipient liver cells. The knockdown of PTEN attenuated the proliferation of HCC cells treated with the exosomal miR-155. Moreover, nude-mouse experiment results revealed a promotional effect of the exosomal miR-155 on HCC cell-acquired xenografts. Conclusions Our study indicated that exosomal-specific miR-155 transfers to adjacent and/or more distant cells and stimulates the proliferation of HCC cells.","PeriodicalId":18491,"journal":{"name":"Medical Science Monitor Basic Research","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2019-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86286759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Experiences of Screening for Human Immunodeficiency Virus, Viral Hepatitis B, and Viral Hepatitis C Infections at a Hospital in Thailand: Test Utilization and Outcomes","authors":"V. Lekskulchai","doi":"10.12659/MSMBR.918374","DOIUrl":"https://doi.org/10.12659/MSMBR.918374","url":null,"abstract":"Background To prevent the transmission of HIV and hepatitis B and C viruses, early detection is necessary; however, in the early stage, most infected people are symptomless. Screening for these infections should be targeted to certain clinical settings to increase the early detection rate. Material/Methods This retrospective study was conducted by analyzing data from patients’ medical records to determine how the screening tests for these viral infections were utilized and what the clinical outcomes from the test utilization were. Results From 11 676 collected records, the screening tests for HIV, HBV, and HCV infections were utilized in 871, 556, and 236 cases, respectively. The tests for HIV and HCV were utilized the most in people with chronic non-infectious diseases, while the test for HBV infection was utilized the most in pregnant women. The positive results of these tests were highly found in the group of patients with acute non-infectious diseases. HIV infection was newly detected in 1.38% of patients, and HBV and HCV infections were newly detected in 5.58% and 2.12%, respectively. Conclusions Screening for HIV and HBV infections was performed according to the guidelines of the national HIV and HBV programs. The Outpatient Department (OPD) and medical ward may be the most appropriate clinical settings for HIV screening because most patients are there and blood tests are often ordered there, too. The national programs helped slow the rates of HIV and HBV infections in this community.","PeriodicalId":18491,"journal":{"name":"Medical Science Monitor Basic Research","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2019-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91189398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Features of 4 Novel NOTCH3 Mutations of Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy in China","authors":"Weiwei Qin, Z. Ren, M. Xia, Miaomiao Yang, Yingying Shi, Yue Huang, Xiangqian Guo, Jiewen Zhang","doi":"10.12659/MSMBR.918830","DOIUrl":"https://doi.org/10.12659/MSMBR.918830","url":null,"abstract":"Background This study aimed to identify NOTCH3 mutations and describe the genetic and clinical features and magnetic resonance imaging results in 11 unrelated patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) from Henan province in China. Material/Methods NOTCH3 was directly sequenced in 11 unrelated patients of Chinese descent. The clinical presentations and magnetic resonance imaging features were retrospectively analyzed in the 11 index patients with a definite diagnosis. Results Seven different mutations were identified in 11 unrelated patients, including 4 novel mutations (p.P167S, p.P652S, p.C709R, and p.R1100H) in China and 3 reported mutations (p.C117R, p.R578C, and p.R607C). Four novel mutations (p.P167S, p.P652S, p.C709R, and p.R1100H) were predicted to be probably pathogenic using an online pathogenicity prediction program through comprehensive analysis. Clinical presentations in symptomatic patients included stroke, cognitive decline, psychiatric disturbances, and migraine. Multiple lacunars infarcts and leukoaraiosis were detected on MRI in most symptomatic patients, while white-matter lesions were identified in the temporal pole or the external capsule in all affected patients. Conclusions The mutation spectrum of CADASIL patients from Henan province in China displayed some differences from that of those reported previously. DNA sequencing was used to diagnose all 11 patients as having CADASIL, and we found 4 novel mutations. The present results further contribute to the enrichment of NOTCH3 mutation databases.","PeriodicalId":18491,"journal":{"name":"Medical Science Monitor Basic Research","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2019-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86151278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Benefit of Reducing Body Weight Loss with A Nutritional Support Pathway in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation.","authors":"Takashi Aoyama, Kanako Yoshitsugu, Masafumi Fukaya, Tetsuo Kume, Miho Kawashima, Kazuko Nakajima, Hidekazu Arai, Osamu Imataki, Terukazu Enami, Raine Tatara, Takashi Ikeda","doi":"10.12659/MSMBR.917329","DOIUrl":"10.12659/MSMBR.917329","url":null,"abstract":"<p><strong>Background: </strong>This retrospective, historically controlled investigative study examined the benefit of a nutritional support pathway that included nutritional education before the start of conditioning and emphasized oral nutrition in response to nutrition-related adverse events in patients undergoing hematopoietic stem cell transplantation (HSCT).</p><p><strong>Material and methods: </strong>Participants were patients undergoing allogeneic HSCT; 46 were in the control group (i.e., did not follow our nutritional pathway) and 36 were in the group that underwent nutritional intervention (enhanced nutrition group). We compared the following parameters between groups from the day before the start of conditioning to the day after completion of parenteral nutrition (PN): percent loss of body weight (%LBW), percent loss of skeletal muscle mass (%LSMM), and estimated basal energy expenditure (EBEE) sufficiency rate. The relationship between each parameter and %LBW was also examined. We also compared nutritional indices, gastrointestinal graft versus host disease (GvHD) grade, oral energy intake, and %LBW between groups.</p><p><strong>Results: </strong>There was a relationship between %LBW, %LSMM, and EBEE sufficiency rate in both groups. Compared with the control group, the enhanced nutrition group had significantly improved energy intake amount, EBEE sufficiency rate, PN duration, and oral energy intake over time. The enhanced nutrition group also had increased oral energy intake, no difference in gastrointestinal GvHD grade, and improved %LBW compared with the control group.</p><p><strong>Conclusions: </strong>Use of our nutritional support pathway in patients undergoing HSCT may be beneficial for %LBW and gastrointestinal GvHD grade, enabling early enhanced nutritional intervention after HSCT.</p>","PeriodicalId":18491,"journal":{"name":"Medical Science Monitor Basic Research","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2019-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6754707/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88026063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antifungal and Synergistic Effects of the Ethyl Acetate Extract of Tanacetum vulgare (L.) Against Candida albicans.","authors":"Ariana Kameri, Ferit Koçani, Zeqir Hashani, Kemajl Kurteshi, Blerim Kamberi, Arsim Kurti, Arben Haziri","doi":"10.12659/MSMBR.917394","DOIUrl":"10.12659/MSMBR.917394","url":null,"abstract":"<p><p>BACKGROUND With the continued demand for new, effective, and safe endodontic therapies, the aim of this study was assessment of efficiency of the ethyl acetate (EthOAc) extract of Tanacetum vulgare (L.) against Candida albicans. MATERIAL AND METHODS The antifungal effectiveness of the EthOAc extract of T. vulgare was determined using the agar disk diffusion method. The inhibition zones induced by the EthOAc extract were compared after 5 minutes, 60 minutes, and 24 hours to those induced by standard solutions (2% chlorhexidine, saturated calcium hydroxide, and 2% sodium hypochlorite). Statistical analysis of the results was performed using the Kruskal-Wallis test and one-way ANOVA. RESULTS The inhibition zone of chlorhexidine against C. albicans was 30.3-19.3 mm, but in combination with EthOAc extract (100 mg/mL) of T. vulgare, this inhibition was from 32.7-30 mm, indicating that this combination exerted a marked synergistic effect against C. albicans. The inhibition zone of sodium hypochlorite (69.7-65 mm) was higher than the inhibition zone of EthOAc extract and chlorhexidine. The combination of EthOAc extract with sodium hypochlorite resulted in a loss of antifungal activity. Furthermore, the activity of the EthOAc extract against C. albicans was decreased after mixing the extract with dentine at a concentration of 25 mg/50 µL (30.3-20.7 mm). The EthOAc extract did not show a genotoxic effect on lymphocyte cells. CONCLUSIONS The EthOAc extract of T. vulgare may be a useful tool to discover natural bioactive agents that have antifungal activity against C. albicans and could be used as endodontic therapies.</p>","PeriodicalId":18491,"journal":{"name":"Medical Science Monitor Basic Research","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2019-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6730044/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79941600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fibromyalgia and its New Lessons for Neuropsychiatry.","authors":"Laura Duque,&nbsp;Gregory Fricchione","doi":"10.12659/MSMBR.915962","DOIUrl":"https://doi.org/10.12659/MSMBR.915962","url":null,"abstract":"<p><p>Fibromyalgia (FM) is a centralized pain state that until recently has been shrouded in mystery and questionable as a disease entity in the eyes of many physicians, who considered it purely psychogenic. Fibromyalgia is now thought of as a discrete diagnosis with a clustering of symptoms characterized by central nervous system pain amplification along with anergia, memory loss, disturbances of mood, and sleep disruption. The condition is present in approximately 2% to 8% of the population. We review the link between inflammatory mechanisms and FM from a neuropsychiatric perspective. Recent studies are pointing to a neuroinflammatory etiology that may open up more effective treatment strategies in the future. Better conceptualization of FM may also elucidate a neuropsychiatric understanding of how nociception, dysthymia, and suicidality co-develop and feed off one another.</p>","PeriodicalId":18491,"journal":{"name":"Medical Science Monitor Basic Research","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2019-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.12659/MSMBR.915962","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37389935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"microRNA-211-3p has a Role in the Effects of Lipopolysaccharide on Endoplasmic Reticulum Stress in Cultured Human Skin Fibroblasts.","authors":"Yongxiang Wang,&nbsp;Chunyan Wang","doi":"10.12659/MSMBR.915379","DOIUrl":"https://doi.org/10.12659/MSMBR.915379","url":null,"abstract":"<p><p>BACKGROUND Lipopolysaccharide (LPS) in bacterial infection of skin wounds delays wound healing. This study aimed to investigate the effects of LPS and endoplasmic reticulum stress in cultured skin fibroblasts and microRNA-211-3p (miR-211-3p) signaling. MATERIAL AND METHODS Human skin fibroblasts were cultured in increasing concentrations of LPS at 0 ng/ml, 5 ng/ml, 10 ng/ml, and 20 ng/ml for 0, 12 h, 24 h, 36 h, and 48 h. Cell proliferation was determined using the MTT assay. Protein expression levels of the transcription factors GRP78, CHOP, p-JNK, and the endoplasmic reticulum stress apoptosis proteins, caspase-12 and Bcl-2, were determined by Western blot. The expression of miR-211-3p in human skin fibroblasts was detected by quantitative polymerase chain reaction (qPCR). RESULTS Cell proliferation of human skin fibroblasts decreased with increasing concentrations of LPS in a dose-dependent and time-dependent way. Protein levels of GRP78, CHOP, p-JNK, caspase-12, and Bcl-2 were increased 8 h and 12 h after LPS treatment compared with 0 h and 4 h after treatment. However, the expression of miR-211-3p was decreased in human skin fibroblasts after treatment with LPS. When miR-211-3p was overexpressed, the endoplasmic reticulum stress/CHOP related proteins, including GRP78, CHOP, p-JNK, caspase-12, and Bcl-2 were unchanged after the addition of LPS. Overexpression of miR-211-3p also reduced inhibitory effects of LPS on the growth of human skin fibroblasts. CONCLUSIONS This study showed that microRNA-211-3p had a role in the effects of LPS on endoplasmic reticulum stress and CHOP activation in cultured human skin fibroblasts.</p>","PeriodicalId":18491,"journal":{"name":"Medical Science Monitor Basic Research","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2019-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/96/b6/medscimonitbasicres-25-164.PMC6607940.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37075111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mental Wellbeing, Quality of Life, and Perception of Chronic Illness in Yoga-Experienced Compared with Yoga-Naïve Patients.","authors":"Shirley Telles,&nbsp;Ram Kumar Gupta,&nbsp;Ankur Kumar,&nbsp;Deepak K Pal,&nbsp;Deepshikha Tyagi,&nbsp;Acharya Balkrishna","doi":"10.12659/MSMBR.914663","DOIUrl":"https://doi.org/10.12659/MSMBR.914663","url":null,"abstract":"<p><p>BACKGROUND Perception of chronic illness and a positive outlook improve recovery, and yoga can improve wellbeing. This study aimed to compare perception, mental wellbeing, and quality of life in yoga-experienced compared with yoga-naïve patients with chronic illness and to determine whether the duration of yoga practice in the yoga-experienced group had any correlation with the perception of illness, mental wellbeing, and quality of life. MATERIAL AND METHODS A cross-sectional comparative study recruited 419 patients with chronic non-communicable disease. Yoga-experienced patients (n=150) (mean age, 41.9±13.6 years) and yoga-naïve patients (n=269) (mean age, 41.2±12.6 years) were assessed for the perception of their illness, mental wellbeing, and quality of life using the Warwick-Edinburgh mental wellbeing scale (WEMWBS) and the World Health Organization quality of life (WHOQOL-BREF) self-reporting questionnaire. RESULTS The yoga-experienced group had significantly increased mental wellbeing, personal control as a dimension of their perception of illness, and psychological and environmental quality of life compared with the yoga-naïve group (all, p<0.05), when comparisons were made using the Mann-Whitney U test. The duration of yoga practised in months was positively-correlated with mental wellbeing and different aspects of quality of life. There was a negative correlation with the perception of illness suggesting that the illness was perceived to be less severe (all, p<0.05) when correlations were made using Spearman's rank correlation coefficient. CONCLUSIONS In patients with chronic illness, yoga improved mental wellbeing, aspects of quality of life, and resulted in a positive perception of illness.</p>","PeriodicalId":18491,"journal":{"name":"Medical Science Monitor Basic Research","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2019-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.12659/MSMBR.914663","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37253998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Urocortin Induces Phosphorylation of Distinct Residues of Signal Transducer and Activator of Transcription 3 (STAT3) via Different Signaling Pathways.","authors":"Giovanni Corsetti,&nbsp;Zhaokan Yuan,&nbsp;Claudia Romano,&nbsp;Carol Chen-Scarabelli,&nbsp;Alessandro Fanzani,&nbsp;Evasio Pasini,&nbsp;Francesco S Dioguardi,&nbsp;Francesco Onorati,&nbsp;Daniele Linardi,&nbsp;Richard Knight,&nbsp;Hemang Patel,&nbsp;Giuseppe Faggian,&nbsp;Louis Saravolatz,&nbsp;Tiziano M Scarabelli","doi":"10.12659/MSMBR.914611","DOIUrl":"https://doi.org/10.12659/MSMBR.914611","url":null,"abstract":"<p><p>BACKGROUND Urocortin (Ucn) is a member of the hypothalamic corticotrophin-releasing factor family and has been shown to reduce cell death in the heart caused by ischemia/reperfusion (I/R) injury. Signal transducer and activator of transcription 3 (STAT3) is a transcription factor known to function as a pro-survival and anti-apoptotic factor, whose activation depends on a variety of cytokines, including IL-6. A recent study demonstrated that urocortin induced IL-6 release from cardiomyocytes in a CRF-R2-dependent manner, suggesting a possible link between CRF-R2 stimulation and STAT3 activation. MATERIAL AND METHODS Experimental work was carried out in HL-1 cardiac myocytes exposed to serum starvation for 16-24 h. RESULTS Ucn stimulation led to IL-6 expression and release from mouse atrial HL-1 cardiomyocytes. Ucn treatment led to rapid phosphorylation of JAK2, which was blocked by the protein synthesis inhibitor cycloheximide or the JAK inhibitor AG490. Urocortin treatment induced STAT3 phosphorylation at Y705 and S727 through transactivation of JAK2 in an IL-6-dependent manner, but had no effect on STAT1 activity. Kinase inhibition experiments revealed that urocortin induces STAT3 S727 phosphorylation through ERK1/2 and Y705 phosphorylation through Src tyrosine kinase. In line with this finding, urocortin failed to induce phosphorylation of Y705 residue in SYF cells bearing null mutation of Src, while phosphorylation of S727 residue was unchanged. CONCLUSIONS Here, we have shown that Ucn induces activation of STAT3 through diverging signaling pathways. Full understanding of these signaling pathways will help fully exploit the cardioprotective properties of endogenous and exogenous Ucn.</p>","PeriodicalId":18491,"journal":{"name":"Medical Science Monitor Basic Research","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2019-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.12659/MSMBR.914611","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37390235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}