Objective To observe the expression of a two-pore domain K+ channel KCNK16 in rat islets,and to explore its regulation by insulin secretagogues.Methods Real time-PCR and immunohistochemistry were employed to observe the expression of KCNK16 in rat islets and other tissues.Rat islets were exposed to glucose,prolactin,palmitate,and trichostatin A (TSA) for 24 h and KCNK16 expression were determined by realtime-PCR and Western blot.Glucose-and KCl-stimulated insulin secretion were assayed by ELISA after islets were exposed to TSA for 24 h.The dose-and time-dependent effects of TSA on KCNK16 expression in INS1-E cells were determined by RTPCR.Results KCNK16 was highly expressed in rat islets.Glucose,prolactin,and palmitate did not affect the expression of KCNK16 in rat islets.TSA treatment significantly potentiated glucose-and KCl-stimulated insulin secretion in isolated rat islets (P < 0.05),along with decreased KCNK16 mRNA and protein expressions (P < 0.01).TSA inhibited KCNK16 expression in a dose-and time-dependent manner in INS1-E cells (P<0.05).Conclusion KCNK16 is exclusively and highly expressed in rat islets and its expression can be down-regulated by TSA treatment.It is possible that TSA enhances insulin secretion via decreasing KCNK16 expression.
This paper presents a multi-label classification method for weak labeling, which deals with data by using the way of pairs constraints projection based on similarity. The method can make better use of characteristics of the sample with weak label and improve the classification performance.
Endothelial dysfunction as well as abnormal thyroid hormone levels may be responsible for increased cardiovascular risk in Graves' disease (GD). Asymmetric dimethylarginine (ADMA) and N-terminal-pro-B-type natriuretic peptide (NT-proBNP) are new markers of endothelial and myocardial dysfunction, respectively. The purpose of this study was to investigate the relationship among the serum levels of ADMA, NT-proBNP, and thyroid hormones in GD patients. This was a cross-sectional investigation conducted in a university teaching hospital. Two hundred and thirty-nine GD (Female: 182, Male: 57) patients and 81 normal controls were enrolled in this study. Serum levels of ADMA were positively related with FT3 (r = 0.584, P < 0.001), FT4 (r = 0.551, P < 0.001), and TRAb levels (r = 0.502, P < 0.001). Serum NT-proBNP levels were positively associated with FT3 (r = 0.243, P < 0.001) and FT4 levels (r = 0.274, P < 0.001), as well as heart rate (r = 0.271, P < 0.03). The elevation of serum ADMA and NT-proBNP levels were also observed in patients with controlled hyperthyroidism. It is thus concluded that serum ADMA and NT-proBNP levels were increased in GD patients. Future studies may determine the usefulness of these two biomarkers to detect early signs of endothelial dysfunction, vascular stiffness, and fluid volume in GD patients.
The expression of X-linked inhibitor of apoptosis (XIAP) and the P2X7 receptor were demonstrated in a variety of tumors. The purpose of the present study was to investigate the associations of XIAP and P2X7 receptor expression with the clinicopathological features of patients with papillary thyroid carcinoma (PTC). In this cross-sectional study, a total of 62 cases were examined, including 43 patients with PTCs and 19 with benign nodular goiters. XIAP and P2X7 receptor expression were examined by immunohistochemical methods on formalin-fixed, paraffin-embedded thyroid tissues. The staining intensity and extent were evaluated and scored using a semi-quantitative method. The immunohistochemical staining score integrating the intensity and extent of XIAP and P2X7 receptors in PTCs was higher than in nodular goiters. XIAP (OR: 5.6, 95% CI: 1.5-21.1, P=0.009) and P2X7 receptor (OR: 6.1, 95% CI: 1.5-24.4, P=0.007) expression were associated with lymph node metastasis in PTCs. In logistic regression analysis, P2X7 receptor expression, tumor size, and capsular infiltration were predictors for lymph node metastasis (P=0.001). Our results suggested that XIAP and P2X7 receptor expression may predict the aggressiveness of PTC.
Objective To study the expressions and significance of p73 in thyroid carcinoma tissue.Methods The expression of p73 was investigated with immunohistochemistry in 107 specimens of thyroid carcinoma and 31 specimens of benign thyroid disorders.Results The positive rate of p73 in the thyroid carcinoma group was 66.4% and that in the benign thyroid tissue was 12.9% respectively,the difference between the rates of the two groups was statistically significant(P<0.05).Conclusion p73 could be involved in the development of thyroid carcinoma.
BACKGROUND The BRAF mutation V600E (BRAF(V600E)) is the most common genetic alteration in papillary thyroid carcinoma (PTC), while overexpression of X-linked inhibitor of apoptosis (XIAP) has been found in various tumors. Both of these events are implicated in carcinogenesis, tumor progression, recurrence, etc. There are few reports, however, of the BRAF(V600E) mutation and XIAP overexpression in PTC patients. The aim of this study was to investigate the frequency of the BRAF(V600E) mutation in PTC and its relationship to clinicopathological parameters and the expression of XIAP. METHODS Genomic DNA was extracted from 123 paraffin-embedded PTC tumor tissue samples and amplified for analysis of the V600E mutation in exon 15 of the BRAF gene by polymerase chain reaction. XIAP expression was examined by immunohistochemical methods in 46 PTCs, 18 benign nodular goiters, and 10 Hashimoto's thyroiditis samples. RESULTS The BRAF(V600E) mutation was found in 34.1% of PTC, and was especially prevalent in the classic type. BRAF(V600E) was significantly correlated with younger age at diagnosis (p = 0.026), tumor size (p = 0.009), and histological variants (p = 0.024). There was a trend towards association with extrathyroidal invasion (p = 0.067). By logistic regression analysis, a significant relationship was found between tumor size and the BRAF(V600E) mutation (p = 0.03). XIAP was expressed in 82.6% of PTCs, which was a higher percentage than observed in the group of benign thyroid disorders (35.7%, p < 0.001). Neither the intensity (p = 0.611) nor the extent (p = 0.723) of XIAP staining was correlated with the presence of BRAF(V600E) in PTC patients. CONCLUSIONS These data indicate that BRAF(V600E) is associated some of the aggressive clinicopathological features of PTC including younger age at diagnosis, larger tumor size, and classic histological type, as well as also extrathyroidal invasion. XIAP-positive staining was more prevalent in PTCs than in the benign thyroid disorders. Although BRAF(V600E) and XIAP expression are commonly seen in PTC, their presence together seems unrelated.
Objective To investigate the changes of serum N-terminal-pro-B-type natriuretic peptide (NT-proBNP) concentration in patients with Graves' disease (GD) and its clinical significance. Methods Two hundred and sixty-nine patients with GD were enrolled in this study. Serum concentrations of thyroid hormones,TRAb, and NT-proBNP were measured. Results Serum NT-proBNP levels were positively associated with FT3(r=0.260, P<0.01), FT4(r=0.297,P<0.01) and heart rate (r=0.251, P<0.05) independent of age,sex and body mass index (BMI). The difference of serum NT-proBNP concentrations between newly-onset and treated patients existed (P<0.01) after the adjustment for thyroid hormone levels, age, sex and BMI. Serum FT4level exerted a significant impact on NT-proBNP level (P <0.01). Serum NT-proBNP increased even in patients with controlled thyroid function. Conclusion Serum NT-proBNP level in patients with GD increases with elevation of FT4 independent of sex, age and BMI. The measurement of serum NT-proBNP concentration appears to be helpful to monitor the alteration of vascular stiffness and fluid volume in GD patients, and may provide useful evidence for early intervention of cardiovascular disease induced by hyperthyroidism.
To investigate the circadian rhythmicity of adiponectin in patients with Cushing's syndrome and obesity, as well as in normal subjects. The effects of glucocorticoids, insulin and leptin on the secretion of adiponectin were also explored.15 patients with Cushing's syndrome and 10 with obesity as well as 9 normal subjects were recruited and their serum adiponectin, glucocorticoids, insulin and leptin levels were determined 6 times a day (8:00, 12:00, 16:00, 20:00, 24:00, 3:00).Circadian rhythmicity of adiponectin was not observed, but the adiponectin levels in patients with obesity were lower than those in the normal subjects at all 6 time spots. The area under curve (AUC) of serum adiponectin concentrations were significantly negatively correlated with body mass index (BMI, r = 0.46, P < 0.01), waist circumference (r = -0.33, P < 0.05) and insulin AUC (r = -0.36, P < 0.05). A multiple linear regression analysis revealed that BMI and waist circumference were two significant independent parameters of the plasma adiponectin level. The adiponectin levels did not manifest any change after short term dexamethasone administration with both high and low doses, but were obviously decreased after surgery.Neither long-term endogenous hyperglucocorticoidism nor short-term dexamethasone administration affects the serum adiponectin levels and the serum adiponectin concentrations remain unchanged even with elevated postprandial insulin levels.
Objective:To observe the effect of Erxian Decoction(EXD) and its two dissected recipes,the recipe of warming Kidney(WK) and the recipe of norurishing Yin (NY),on gonadotropin releasing hormone (GnRH) gene transcription and expression of CT_(1-7) cell line,using serum-pharmacological method.Methods:SD rats were medicated with EXD,WK and NY for 4 consecutive days,their sera were collected 1h after the last medication for in vitro cell culture.GnRH secretion of GT_(1-7) cells was determined by radioimmunoassay and the effect of the treatment on GnRH mRNA of GT_(1-7) cells were observed by Northern bolt.Results:All the three treatments could promote the secretion of GnRH,the effect of EXD was the best.After being cultured for 24 hrs,the GnRH mRNA level in the EXD and WK group showed a trend of decreasing,but in the NY group,it increased significantly after 48 hrs culture.Conclusion:TcM theory of “Kidney governs reproduction” may be related with the GnRH neurons in hypothalamus and its function in regulating gonad axis,EXD and its dissected recipes could directly regulate the secretion and gene expression of GnRH of GT_(1-7) cells.