Lin28a up-regulation is associated with the formation of restenosis via promoting proliferation and migration of vascular smooth muscle cells.

To explore the potential role of Lin28a in the development of restenosis after percutaneous transluminal angioplasty, double-balloon injury surgery and mono-balloon injury surgery were used to establish restenosis and atherosclerosis models, respectively, so as to better distinguish restenosis from atherosclerotic lesions. Immunohistochemical analysis revealed that significantly higher expression of Lin28a was observed in the iliac arteries of restenosis plaques than that of atherosclerosis plaques. Immunofluorescence studies showed the colocalization of Lin28a with α-smooth muscle actin in restenosis plaques, rather than in atherosclerosis plaques, which suggested that Lin28a might be related to the unique behaviour of vascular smooth muscle cells (VSMCs) in restenosis. To further confirm above hypothesis, Lin28a expression was up-regulated by transfection of Lenti-Lin28a and inhibited by Lenti-Lin28a-shRNA transfection in cultured VSMCs, and then the proliferation and migration capability of VSMCs were detected by EdU and Transwell assays, respectively. Results showed that the proliferation and migration of VSMCs were significantly increased in accordance with the up-regulation of Lin28a expression, while above behaviours of VSMCs were significantly suppressed after inhibiting the expression of Lin28a. In conclusion, the up-regulation of Lin28a exerts its modulatory effect on VSMCs' proliferation and migration, which may play a critical role in contributing to pathological formation of restenosis.

Integrated analysis identifies DUSP5 as a novel prognostic indicator for thyroid follicular carcinoma.

BACKGROUND: Differentiated thyroid cancer involves thyroid follicular carcinoma (FTC) and papillary thyroid carcinoma (PTC). Patients with FTC have a worse prognosis than those with PTC for early metastasis through blood of FTC. However, the mechanism of poor prognosis of FTC is still unclear. Here, we aim to evaluate the role of DUSP5 in the prognostic evaluation of FTC. METHOD: We searched the Gene Expression Omnibus (GEO) database for the differentially expressed genes (DEGs) between FTC and PTC, and then combined with survival analysis of cBioPortal database to locate the gene significantly related to prognosis. Tissue microarrays and clinical tissues were used to examine DUSP5 expression by immunohistochemical (IHC) staining between FTC and PTC tissues. In vitro experiment, proliferation, migration and invasion of FTC were observed after regulation of DUSP5 by transfection of siRNA and plasmids, respectively. RESULTS: After searching the GEO database, 26 DEGs were found. DUSP5 was significantly associated with prognosis of FTC in combination with survival analysis. Data of IHC staining showed lower expression of DUSP5 in FTC compared to PTC tissues. Furthermore, overexpression of DUSP5 inhibited the proliferation, migration and invasion accompanied with low level of MMP9 and Vimentin and high level of E-cadherin. Nevertheless, inhibition of DUSP5 ameliorated above damaging effect on the proliferation, migration and invasion. CONCLUSION: DUSP5 was differentially expressed in FTC and PTC tissues. Low level of DUSP5 in FTC participates in the high frequency of metastasis, and further contributes to poor prognosis of FTC. DUSP5 could be served as a novel therapeutic target for FTC.

Efficacy of low-protein diet for diabetic nephropathy: a systematic review of randomized controlled trials.

BACKGROUND: A low-protein diet (LPD) is believed to be beneficial in slowing the progression of kidney disease. It is reported that low protein diet can improve protein, sugar and lipid metabolism, and reduce the symptoms and complications of renal insufficiency. However, there has been controversial regarding the effects of protein restriction on diabetic nephropathy (DN). OBJECTIVE: To investigate the efficacy of LPD on renal function in patients with type 1 or 2 DN by meta-analysis of randomized controlled trials (RCTs). DESIGN: PubMed, MEDLINE, EMBASE and China National Knowledge Infrastructure databases were searched. Eleven randomized controlled trials met the inclusion criteria, of which 10 were English and 1 was Chinese. The primary outcome was a change in glomerular filtration rate (GFR). The secondary outcome was a change in proteinuria. Random-effects models were used to calculate the standardized mean difference (SMD) and the corresponding 95% confidence intervals (CI). Subgroup analyses were also performed. RESULTS: Our research indicated that LPD was not associated with a significant improvement in GFR (1.59 ml · min-1 · 1.73 m-2, 95% CI -0.57, 3.75, I2 = 76%; p = 0.15). This effect was consistent across the subgroups regardless of type of diabetes, course of diabetes and intervention period. Our results also showed that there was no significant difference on improvement of proteinuria in patients of LPD and those in normal-protein diet groups (- 0.48, 95%CI-1.70, 0.74, I2 = 94%, p = 0.44). Subgroup analysis revealed that LPD resulted in increased excretion of proteinuria in patients with type 2 diabetes (1.32, 95% CI 0.17, 2.47, I2 = 86%, p = 0.02). CONCLUSION: The present research showed that LPD was not significantly associated with improvement of renal function in patients with either type 1 or 2 diabetic nephropathy. Although these results do not completely eliminate the possibility that LPD is beneficial for patients with diabetic nephropathy, it does not seem to be significant benefit to renal function.

Methylation of sodium iodide symporter promoter correlated with aggressiveness and metastasis in papillary thyroid carcinoma: a meta-analysis.

BACKGROUND: Methylation of sodium iodide symporter promoter has been reported to increase the incidence of papillary thyroid carcinoma (PTC). In this meta-analysis stratified via methylation of sodium iodide symporter promoter, we evaluate the relationship between methylation of sodium iodide symporter promoter and PTC. The association between methylation with aggressiveness and metastasis potential of PTC is also discussed. METHODS: We searched electronic databases for original articles and references of included studies both in English and Chinese from 1966 to 2014. Two reviewers selected the case-control study and extracted data from relevant literature independently. RESULTS: Seven articles, including 360 cases and 268 controls, were involved in this meta-analysis. The prevalence of PTC in patients with methylated sodium iodide symporter promoter was significantly higher than those with non-methylated promoter (OR=7.36, 95% CI: 4.25-12.74, P<0.001). Stratified analysis showed that PTC patients with multiple lesions, capsule invasion and lymphatic metastasis had significantly higher rates of methylation (OR=2.22, 95% CI: 1.12-4.41, P=0.02; OR=2.14, 95% CI: 1.12-4.08, P=0.02; OR=3.56, 95% CI: 1.97-6.46, P<0.0001). But no relationship was found among the methylation of sodium iodide symporter and age, gender and size of tumor. CONCLUSIONS: The methylation of sodium iodide symporter promoter is related with PTC and its aggressive and metastatic potential. Due to the limited sample size, more clinical researches should be taken in the future.

New agent to treat advanced or metastasized thyroid cancer, its efficacy, safety, and mechanism.

BACKGROUND: Vandetanib is the first US Food and Drug Administration approved agent to treat advanced or metastasized thyroid cancer. To gain a better understanding of the drug, we conducted a systematic review of its efficacy and safety in patients with thyroid cancers. METHODS: Trial data was retrieved from Pubmed, EMBASE, Medline, China National Knowledge Infrastructure, and the Cochrane database without restrictions on language. A systematic review of the literature was performed to assess median progression-free survival (PFS) and adverse events associated with vandetanib therapy for advanced or metastasized thyroid cancers. RESULTS: Vandetanib statistically prolonged PFS in comparison with the placebo (30.5 vs. 19.3 months, hazard ratio 0.46), It even prolonged PFS in surgically unresectable or metastatic differentiated thyroid cancer cases compared with the placebo (11.1 vs. 5.9 months, hazard ratio 0.63). Rash, diarrhea, neutropenia, and hypertension were the most frequent side effects. CONCLUSION: Vandetanib can significantly improve PFS. Though it has some side effects, it is still a promising agent in the treatment of advanced or metastasized thyroid cancer, especially in those with metastasized or advanced medullary thyroid carcinoma.

Association between sodium iodide symporter and differentiated Thyroid cancer: a meta-analysis of 9 studies.

CONTEXT: As many studies proved that sodium iodide symporter (NIS) plays a key role in radioactive iodide (RAI) therapy of thyroid cancer, however, a growing number of studies suggests that part of differentiated thyroid carcinomas (DTC) with overexpression of NIS are insensitive to RAI well. OBJECTIVE: The aim of this meta-analysis is to assess the expression of NIS in differentiated thyroid cancer, compared with normal thyroid tissue. DATA SOURCES: PUBMED, Sinomed, CNKI, Wanfang and VIP were searched for relevant case-control studies up to now. STUDY SELECTION: Studies that concerning the qualitative expression NIS in DTC were included. DATA EXTRACTION: Working independently, authors used a standard form to extract data. For quality assessment, Newcastle-Ottawa Scale (NOS) were applied. DATA SYNTHESIS: Totally nine eligible studies included, involving 765 cases and 473 controls. The results revealed that the expression of NIS had a statistically increased in DTC, compared with controls (OddsRadio OR: 1.47, 95% CI: 1.12 to 1.94, Z=2.78, P=0.005). Since the existence of the significant heterogeneity, subgroup analysis and sensitivity analysis were performed and found that the heterogeneity came from the different criteria evaluate positive NIS expression (Liu 2008, Mu 2010) and the small simple size of the control group (Lin. J D2001). The heterogeneity disappeared or dropped to below 50% after remove these studies. CONCLUSION: Our study shows that the expression of NIS is significantly increased in DTC, which could help explain the reason for individual with a poor response to RAI therapy. In other word, the reduced iodide uptake in thyroid cancer may not caused by the decreased expression of NIS, function of NIS protein or its post-transcriptional translocation might be the point.