Sclerostin domain containing protein 1 (SOSTDC1) is down-regulated and acts as a tumor suppressor in some kinds of cancers. However, the expression pattern and biological significance of SOSTDC1 in thyroid cancer are largely unknown. We demonstrated that SOSTDC1 was significantly down-regulated in thyroid cancer. Ectopic over-expression of SOSTDC1 inhibited proliferation and induced G1/S arrest in thyroid cancer cells. Moreover, SOSTDC1 over-expression suppressed the growth of tumor xenografts in nude mice. We also found that elevated SOSTDC1 led to inhibition of cyclin A2 and cyclin E2. Together, our results demonstrate that SOSTDC1 is down-regulated in thyroid cancer and might be a potential therapeutic target in the treatment of thyroid cancer.
Aims/IntroductionTo explore angiopoietin‐like protein 8 (ANGPTL‐8) levels, and its association with hepatocellular lipid content (HCL) and insulin resistance in patients with different extents of non‐alcoholic fatty liver disease (NAFLD).Materials and MethodsIn 48 adults were recruited, of which 12 had no NAFLD (HCL < 5.5%; group 1), 18 had mild NAFLD (5.5% ≤ HCL < 10.0%; group 2) and 18 had moderate‐to‐severe NAFLD (HCL ≥ 10.0%; group 3). The peripheral insulin sensitivity of all participants was monitored by a hyperinsulinemic‐euglycemic clamp (M value), as well as the magnetic resonance image of HCL. Serum ANGPTL‐8, blood glucose levels and lipid profiles were also recorded in the study.ResultsGroup 3 had a worse metabolic profile, and had the highest ANGPTL‐8 level (1,129 ± 351 pg/mL vs 742 ± 252 pg/mL, 765 ± 301 pg/mL, P = 0.001) compared with those in group 1 and group 2. In all metabolic profiles, HCL positively correlated the strongest with ANGPTL‐8 (r = 0.436, P = 0.042). Multivariate stepwise linear regression analysis showed ANGPTL‐8 and alanine aminotransferase were independent determinants of HCL (P = 0.002, P < 0.001, respectively), and these two indexes explained 67.4% of the variation of HCL (P < 0.001).Conclusions
ANGPTL‐8 was positively correlated with hepatocellular lipid content independent of obesity and insulin resistance, indicating that ANGPTL‐8 might be a new and important important predictor of the severity of NAFLD.
Aims/IntroductionOptimal glycemic targets during short‐term intensive insulin therapy in patients with newly diagnosed type 2 diabetes are not standardized. The present study was carried out to determine the optimal glycemic targets during therapy by analyzing the impacts of glucose levels on therapeutic outcomes.Materials and MethodsA total of 95 individuals with newly diagnosed type 2 diabetes were enrolled. Short‐term intensive insulin therapy was carried out using an insulin pump to achieve and maintain glycemic targets (fasting blood glucose ≤6.0 mmol/L, 2‐h postprandial blood glucose ≤7.8 mmol/L) for 14 days, with daily eight‐point capillary blood glucose profiles recorded. Patients were followed up for 1 year after discharge.ResultsIn most participants, the mean blood glucose and glycemic excursion parameters during the therapy were controlled within the normal range. Mean blood glucose was independently associated with amelioration of acute insulin response (r = −0.25, P = 0.015) and 1‐year remission (odds ratio 0.12, 95% confidence interval 0.034–0.426), but negatively associated with more level 1 hypoglycemia (r = −0.34, P = 0.001), although major hypoglycemia was rare. Among mean blood glucose tertiles, patients in the middle (68.7%) and lower (75.0%) tertiles had a higher 1‐year remission rate compared with the upper tertile (32.3%, both P < 0.001), whereas only the middle tertile did not have increased hypoglycemia compared with the upper tertile (8.1 ± 5.4 vs 7.2 ± 3.9 events/person, P = 0.48).ConclusionsStricter glycemic control during short‐term intensive insulin therapy produced more remission despite self‐manageable hypoglycemia. Based on glycemic parameters in the middle mean tertile, we propose new glycemic targets that are approximately 0.4 mmol/L lower than current the targets, as long‐term benefit outweighs short‐term risks.
Fufang Xue Shuan Tong (FXST) capsules, a traditional Chinese medicine, have been used to treat diabetic nephropathy for many years. FXST has been shown to attenuate elevated levels of oxidative stress in the retina of diabetic rats. However, whether FXST protects kidneys through the same mechanism(s) remains unclear. In this study, diabetes was induced in rats by administration of a high-fat diet and low-dose streptozotocin. Rats were administered low (450 mg/kg/day), middle (900 mg/kg/day) or high (1800 mg/kg/day) doses of FXST orally for 3 months. Another group was administered 50 mg/kg/day orally for the same period. The results indicated that all doses of FXST reduced urinary protein excretion and creatinine clearance and ameliorated the diabetic nephropathy-related mesangial matrix expansion. However, only middle and high doses of FXST prevented glomerular hypertrophy in diabetic rats, and the high dose showed the greatest inhibitory effect with regard to mesangial matrix expansion. Furthermore, superoxide dismutase activities were significantly elevated, whereas malondialdehyde levels were significantly reduced in the renal cortex following FXST treatment. The kidney-protective role of FXST is not inferior to that of captopril, one of the most commonly used drugs for the treatment of diabetic nephropathy. In conclusion, FXST retards the progression of diabetic nephropathy, while high-dose FXST shows the most prominent effect in counteracting the pathological changes of diabetic nephropathy. The renoprotective action of FXST is induced by the reduction of oxidative stress in diabetic nephropathy.
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