Transgelin inhibits proliferation and invasion of human thyroid cancer cells by blocking the mitogen-activated protein kinase/extracellular signal-regulated kinase signaling pathway / 中华内分泌代谢杂志

Objective:To explore the role of transgelin(TAGLN) in the occurrence and development of papillary thyroid carcinoma (PTC) and its possible signal pathway.Methods:One hundred cases of PTC tissues and corresponding paracancerous normal thyroid tissues were collected. Realtime quantitative PCR (RT-qPCR), Western blotting, and immunohistochemistry were used to analyze the expression of TAGLN in PTC tissues and corresponding paracancerous normal thyroid tissues. PTC cells were transfected with plasmid and shRNA lentivirus vector respectively to up-regulate or down-regulate the expression of TAGLN in order to detect the effects of them on the proliferation, invasion, and migration by cell proliferation assay(cell counting kit-8, CCK-8)and cell invasion and migration assays (Transwell). The effects of TAGLN on mitogen-activated protein kinase (MAPK)/extracellular-signal regulating kinase (ERK) signal pathway was detected with Western blotting.Results:RT-qPCR showed that there was no difference in the expression of TAGLN mRNA between PTC and corresponding paracancerous normal thyroid tissues ( P>0.05); Western blotting demonstrated that the expression of TAGLN protein in PTC tissues was significantly lower than that in corresponding paracancerous normal thyroid tissues ( P<0.01). Immunohistochemical results revealed that the expression of TAGLN in PTC tissues was significantly lower than that in corresponding paracancerous normal thyroid tissues. Overexpression of TAGLN inhibited the proliferation, invasion, and migration of PTC cells ( P<0.01), but knockdown of TAGLN promoted the proliferation, invasion, and migration of PTC cells ( P<0.01). Overexpression of TAGLN decreased the expression of phosphorylated ERK ( P<0.05), whereas silencing TAGLN increased phosphorylated ERK level in PTC cells( P<0.01). Conclusion:The expression of TAGLN in PTC is significantly decreased. It is related to the occurrence and development of PTC, and its mechanism may be related to MAPK/ERK signal pathway.

Effect of human umbilical cord mesenchymal stem cell exosomes on myocardial fibrosis in rats with Adriamycin-induced dilated cardiomyopathy / 中华实用儿科临床杂志

Objective:To evaluate the effects of human umbilical cord mesenchymal stem cells-derived exosomes (hUCMSCs-ex) injection on cardiac function and myocardial fibrosis in dilated cardiomyopathy (DCM) rats induced by Adriamycin(ADR).Methods:One hundred male SD rats were randomly divided into the normal group (20 rats) and the DCM group (80 rats). The rats in DCM group were treated with ADR by intravenous injection to induce DCM.DCM rats were randomly divided equally into DCM group, low-dose group, medium-dose group and high-dose group which were received intravenous injection 1 mL/kg Dulbecco′s modified eagle medium(DMEM), 20 μg/kg, 100 μg/kg and 250 μg/kg exosomes.After modeling, 10 rats in normal group and 30 rats in DCM group were randomly selected to receive echocardiography to evaluate the cardiac function.After exosomes treatment, 10 rats were randomly selected form each group for echocardiography to evaluate the cardiac function.The morphological changes in myocardial cells were observed by using Masson staining in each group; Western blot detection between groups of rats was used to analyze the expression of myocardial collagen Ⅰ type(COLⅠ), Smad2 and alpha smooth muscle actin (α-SMA).Results:Left ventricular ejection fraction(LVEF) and left ventricular fraction shortening (LVFS)in the DCM group [(64.30±3.51)% and (38.70±2.85)%] were significantly lower than those of the normal group [(78.80±1.52)% and (50.60±1.50)%], and the differences were statistically significant ( t=20.518, 22.311, all P<0.01). The left ventricular end-diastolic diameter(LVEDD) and left ventricular end-systolic diameter (LVESD) [(4.62±0.13) mm and (3.40±0.12) mm] of the DCM group were significantly higher than those of the normal group[(3.29±0.24) mm and (3.16±0.33) mm], and the differences were statistically significant( t=2.854, 3.800, all P<0.01). After exosomes treatment, LVEF[(84.3±2.6)% and (83.4±3.2)%] in the medium-dose and high-dose groups were significantly higher than that in the DCM group [(79.2±2.4)%], and the diffe-rences were statistically significant(all P<0.01). Masson staining found that collagen fibers were less in exosomes treating group than those in the DCM group; Western blot test showed that high-dose exosomes can reduce the expression of α-SMA and Smad2, high-dose and low-dose exosomes can both significantly reduce the expression of COLⅠ. Conclusions:It suggests that exosomes intravenous injection from hUCMSCs-ex can significantly improve myocardial fibrosis in DCM rats induced by ADR and cardiac function.

Relationship between methylation of RSK4 gene and papillary thyroid carcinoma / 中华内分泌代谢杂志

Objective@#To detect the methylation status of ribosomal S6 kinase 4 (RSK4)in papillary thyroid carcinoma (PTC)and to study its correlation with mRNA expression and clinical features.@*Methods@#134 cases PTC tissues and corresponding paracancerous thyroid tissues were collected. DNA methylation status of RSK4 gene in PTC tissues and corresponding paracancerous tissues were analyzed by methylation specific PCR and bisulfite genomic sequencing, and mRNA expression was detected by quantitative realtime PCR. The relationship of DNA methylation status with mRNA expression and clinical features was analyzed.@*Results@#The methylation rate of RSK4 in PTC tissues was significantly higher than that in paracancerous tissues by methylation specific PCR (P<0.05)and bisulfite genomic sequencing (P<0.01). The RSK4 mRNA level in PTC tissues was significantly lower than that in paracancerous tissues (P<0.01). In PTC tissues, RSK4 mRNA expression in methylation group was lower than that in unmethylation group (P<0.01). The RSK4 mRNA level in PTC of methylation was lower than that in paracancerous tissues of methylation (P<0.01); the RSK4 mRNA level in PTC of unmethylation was also lower than that in paracancerous tissues of unmethylated ones (P<0.01). There was relationship of RSK4 hypermethylation with lymphatic metastasis and TNM grade (P<0.05). Serum concentrations of thyroid stimulating hormone, thyroid peroxidase antibody, and thyroglobulin antibody in methylation group were higher than those in unmethylation group (P<0.05).@*Conclusion@#The hypermethylation of RSK4 promoter′s CpG islands might be one of the mechanisms for poor expression of RSK4 in PTC, which may serve as a molecular target of early diagnosis and treatment.

Relationship between methylation of RSK4 gene and papillary thyroid carcinoma / 中华内分泌代谢杂志

Objective To detect the methylation status of ribosomal S6 kinase 4 ( RSK4 ) in papillary thyroid carcinoma ( PTC) and to study its correlation with mRNA expression and clinical features. Methods 134 cases PTC tissues and corresponding paracancerous thyroid tissues were collected. DNA methylation status of RSK4 gene in PTC tissues and corresponding paracancerous tissues were analyzed by methylation specific PCR and bisulfite genomic sequencing, and mRNA expression was detected by quantitative realtime PCR. The relationship of DNA methylation status with mRNA expression and clinical features was analyzed. Results The methylation rate of RSK4 in PTC tissues was significantly higher than that in paracancerous tissues by methylation specific PCR ( P<0.05) and bisulfite genomic sequencing ( P<0. 01 ) . The RSK4 mRNA level in PTC tissues was significantly lower than that in paracancerous tissues ( P<0.01) . In PTC tissues, RSK4 mRNA expression in methylation group was lower than that in unmethylation group ( P<0.01) . The RSK4 mRNA level in PTC of methylation was lower than that in paracancerous tissues of methylation ( P<0. 01);the RSK4 mRNA level in PTC of unmethylation was also lower than that in paracancerous tissues of unmethylated ones ( P<0. 01 ) . There was relationship of RSK4 hypermethylation with lymphatic metastasis and TNM grade ( P<0. 05 ) . Serum concentration, of thyroid stimulating hormone, thyroid peroxidase antibody, and thyroglobulin antibody in methylation group were higher than those in unmethylation group ( P<0.05) . Conclusion The hypermethylation of RSK4 promoter's CpG islands might be one of the mechanisms for poor expression of RSK4 in PTC, which may serve as a molecular target of early diagnosis and treatment.

Prevalence of diabetes mellitus and prediabetes: Changes during past 10 years in Shandong coastal area / 中华内分泌代谢杂志

Objective To determine the changes in the prevalence of type 2 diabetes mellitus and prediabetes in residents aged over 20 years in Shandong coastal areas during years 2004-2014. Methods A random stratified cluster sampling was conducted, and 3 944 inhabitants were investigated in Qingdao, Yantai, Weihai, and Rizhao regions. Results (1)The standardized rate of diabetes mellitus prevalence was 10.36% in 2014, increased by 2.38% as compared with 2004 and 0.85% as compared with 2009 (P<0.05). There were 341 newly diagnosed diabetes mellitus patients, accounting for 57.4% of the diabetes mellitus patients, increased by 6.09% as compared with 2004 and decreased by 4.11% as compared with 2009 (P<0.05). The standardized rate of prediabetes was 12.47% in 2014, increased by 2.63% as compared with 2004 and 0.61% as compared with 2009 (P<0.05). (2) The prevalence of diabetes mellitus and impaired glucose regulation in individuals aged under 50 years in 2014 was significantly higher than that in 2004, but lower than that in 2009 (P<0.05). (3) Compared with 2004 and 2009, the levels of diastolic blood pressure, total cholesterol, low density lipoprotein-cholesterol (LDL-C), and high density lipoprotein-cholesterol in subjects with prediabetes and diabetes mellitus increased significantly in 2014 (all P<0.05). The levels of serum uric acid in subjects with prediabetes and diabetes mellitus decreased significantly in 2014 (P<0.05). (4) The logistic regression analysis showed that the age, body mass index, waist-hip ratio, triglyceride, LDL-C, systolic blood pressure, and diabetic family history were the risk factors for abnormal glucose regulation, while total cholesterol was the protective factor. Conclusions The prevalence of diabetes mellitus and prediabetes increased during 10 years (2004-2014), but the growth rate dropped precipitously during last five years as compared with the first five years. The age of diabetes mellitus onset is getting older in residents of Shandong coastal area, especially in females. Aging, overweight, hypertension, lipid disorders, and diabetic family history were the risk factors of diabetes mellitus.

Correlation study on the serum uric acid and free fatty acid levels of Shandong coastal inhabitants / 中华内分泌代谢杂志

To evaluate the correlation of the serum uric acid and free fatty acid (FFA) levels in Shandong coastal residents. To investigate the correlation between serum uric acid and FFA based on 3860 individuals who have been long staying in Qingdao, Yantai, Weihai, Rizhao with a randomized, stratified cluster sampling method. According to FFA quartile, subjects were divided into four groups: group Q1 of 908, group Q21016, group Q3958, and group Q4978 cases. The prevalence of hyperuricemia and serum uric acid levels increased with the increasing FFA quartile. Compared with Q1, Q2, and Q3 groups, the prevalence of hyperuricemia in Q4 group and the increase of serum uric acid were statistically significant(P<0. 05). And in the group Q4, hyperuricemia prevalence is twice as the group A. According to the serum uric acid level, subjects were divided into the normal uric acid group(n=3331) and the hyperuricemia group ( n = 529). In the hyperuricemia group, their systolic blood pressure, diastolic blood pressure, waist circumference, hip circumference, triglycerides, total cholesterol, low density lipoprotein-cholesterol (LDL-C), glucose, uric acid, FFA, body mass index etc. were significantly higher than those of the normal uric acid group (all P<0. 01), while the high density lipoprotein-cholesterol ( HDL-C), cystatin, glomerular filtration rate (eGFR) are significantly lower than those of the normal uric acid group( all P<0. 01). Serum uric acid levels are positively correlated with systolic and diastolic blood pressures, waist and hip circumferences, triglycerides, total cholesterol, LDL-C, FFA, blood glucose, body mass index (all P<0. 01); and negatively correlated with eGFR (P<0. 01). Multiple regression analysis showed that systolic blood pressure, FFA, total cholesterol, triglycerides, LDL-C, blood glucose, body mass index, eGFR were factors influencing serum uric acid independently. Multivariate binary logistic regression analysis showed that systolic blood pressure, waist circumference, total cholesterol, blood glucose, and FFA are independent risk factors to predict hyperuricemia onset while eGFR is a protective factor. Serum uric acid level is closely related to the free fatty acid, and FFA seems to be involved in the development and progression of hyperuricemia.

Correlation study on the serum uric acid and free fatty acid levels of Shandong coastal inhabitants / 中华内分泌代谢杂志

To evaluate the correlation of the serum uric acid and free fatty acid (FFA) levels in Shandong coastal residents. To investigate the correlation between serum uric acid and FFA based on 3860 individuals who have been long staying in Qingdao, Yantai, Weihai, Rizhao with a randomized, stratified cluster sampling method. According to FFA quartile, subjects were divided into four groups: group Q1 of 908, group Q21016, group Q3958, and group Q4978 cases. The prevalence of hyperuricemia and serum uric acid levels increased with the increasing FFA quartile. Compared with Q1, Q2, and Q3 groups, the prevalence of hyperuricemia in Q4 group and the increase of serum uric acid were statistically significant(P<0. 05). And in the group Q4, hyperuricemia prevalence is twice as the group A. According to the serum uric acid level, subjects were divided into the normal uric acid group(n=3331) and the hyperuricemia group ( n = 529). In the hyperuricemia group, their systolic blood pressure, diastolic blood pressure, waist circumference, hip circumference, triglycerides, total cholesterol, low density lipoprotein-cholesterol (LDL-C), glucose, uric acid, FFA, body mass index etc. were significantly higher than those of the normal uric acid group (all P<0. 01), while the high density lipoprotein-cholesterol ( HDL-C), cystatin, glomerular filtration rate (eGFR) are significantly lower than those of the normal uric acid group( all P<0. 01). Serum uric acid levels are positively correlated with systolic and diastolic blood pressures, waist and hip circumferences, triglycerides, total cholesterol, LDL-C, FFA, blood glucose, body mass index (all P<0. 01); and negatively correlated with eGFR (P<0. 01). Multiple regression analysis showed that systolic blood pressure, FFA, total cholesterol, triglycerides, LDL-C, blood glucose, body mass index, eGFR were factors influencing serum uric acid independently. Multivariate binary logistic regression analysis showed that systolic blood pressure, waist circumference, total cholesterol, blood glucose, and FFA are independent risk factors to predict hyperuricemia onset while eGFR is a protective factor. Serum uric acid level is closely related to the free fatty acid, and FFA seems to be involved in the development and progression of hyperuricemia.