Low Normal TSH Levels and Thyroid Autoimmunity are Associated with an Increased Risk of Osteoporosis in Euthyroid Postmenopausal Women.

BACKGROUND AND OBJECTIVE: Studies on the relationship of thyroid stimulating hormone (TSH) within the reference range and thyroid autoimmunity with osteoporosis have produced conflicting results. The objective of this study was to investigate the association of thyroid function and thyroid autoimmune bodies (TPOAb and TgAb) with osteoporosis in euthyroid postmenopausal women. METHODS: A total of 174 subjects were retrospectively included. Serum TSH, total T3, total T4, TPOAb, TgAb, vitamin D, calcium and bone mineral density were measured. Correlation and logistic multivariate regression analysis were performed. RESULTS: Levels of TSH were lower in osteoporosis group (TSH: 2.03±1.08 vs 2.40±1.24 mIU/L, p=0.040) while TT3 and TT4 levels were similar between the two groups. The positive percentage of anti-TPO antibodies was higher in osteoporosis group (17.9% vs 6.7%, χ2= 5.13, p=0.024) while no significant difference was observed for anti-Tg antibodies (17.9% vs 8.9%, χ2=3.05, p=0.081). The Spearman correlation analysis showed that TSH levels were significantly correlated with lumbar spine BMD (r= 0.161, P=0.035) and femoral neck BMD (r = 0.152, P= 0.045). Logistical regression analysis revealed that low-normal TSH levels and positive TPOAb was an independent risk factor for osteoporosis (OR: 0.698, 95% CI: 0.505-0.965, p=0.030; OR: 3.961, 95% CI: 1.176-13.345, p=0.026 respectively). CONCLUSION: The results showed that low-normal TSH levels and anti-TPO antibodies were independently associated with the presence of osteoporosis in postmenopausal women.

Abdominal aortic calcification and the risk of bone fractures: a meta-analysis of prospective cohort studies.

The relationship between abdominal aortic calcification (AAC) and bone fracture has been examined by some observational studies, but the results remain discordant. Therefore, we aimed to assess the link between them by conducting a meta-analysis of prospective studies. Relevant studies were identified by searching PubMed and EMBASE databases until the end of December 2016. Summary relative risks (RRs) and 95% confidence intervals (CIs) for associations between AAC and fracture risk were estimated with fixed- or random- effects models. Seven prospective studies were included in the final analysis. The summarized RRs of any type of fractures for the highest compared with the lowest category of AAC were 1.64 (95% CI 1.30-2.07, P = 0.000) with mild heterogeneity (I 2 = 30.1%, P = 0.188). Subgroup analysis showed that the association between AAC and fracture was not significantly modified by gender and follow-up length. Risks were similar when analyses were restricted to the studies with adjustment for bone mineral density (BMD) (RR = 1.76, 95% CI 1.31-2.38, P = 0.000, I 2 = 49.1%). For the specific type of fracture, severe AAC was significantly related with hip fracture (RR = 1.64, 95% CI 1.22-2.20, P = 0.001, n = 5), but not with vertebral (RR = 1.45, 95% CI 0.81-2.58, P = 0.213, n = 3) or non-vertebral fracture (RR = 1.35, 95% CI 0.96-1.88, P = 0.081, n = 3). There was no evidence of publication bias. Our findings demonstrated that AAC was significantly and independently associated with a higher fracture risk, especially for hip fracture.

Highly expressed lncRNA CCND2-AS1 promotes glioma cell proliferation through Wnt/ß-catenin signaling.

Glioma is the most common and aggressive primary brain tumor in adults. Long-non coding RNAs (lncRNAs) have been recently shown to play important roles in regulating numerous biological processes both in physiologic and pathologic condition. However, the role of lncRNAs in glioma remains largely unknown. In this study, we firstly found that lncRNA CCND2-AS2 is significantly up regulated in malignant glioma tissues and cell lines. Both loss- and gain-functions assays show that CCND2-AS1 promotes glioma cells proliferation and growth. In addition, we also revealed that highly expressed CCND2-AS1 could enhance Wnt/ß-catenin signaling in glioma. Taken together, our findings revealed a novel lncRNA CCND2-AS1 promotes glioma cell proliferation through Wnt/ß-catenin signaling and CCND2-AS1 might function as a potential novel therapeutic target for the treatment of glioma.

Subclinical hypothyroidism and the risk of metabolic syndrome: A meta-analysis of observational studies.

BACKGROUND: Observational studies on the association between subclinical hypothyroidism (SCH) and metabolic syndrome (MetS) have produced inconsistent results. Therefore, we performed a meta-analysis to evaluate the effect of SCH on the risk of MetS. METHODS: Multiple databases were searched to identify studies on the association between SCH and the risk of MetS, up to February 2015. Relevant information for analysis was extracted. A random-effects model was used to calculate the pooled risk estimates. RESULTS: 9 studies (7 cross-sectional and 2 case-control studies) were included. The pooled odds ratio (OR) for MetS comparing SCH with euthyroid subjects was 1.31 (95%CI: 1.08 to 1.60, p = 0.006, I(2) = 50%). Subgroup analyses by countries revealed a significant association for the studies from Asian (OR = 1.244, 95% CI: 1.030-1.503, I(2) = 25%) other than non-Asian (OR = 1.548, 95% CI: 0.925-2.591, I(2) = 73.5%) countries. A positive association was identified in the IDF subgroup (OR = 1.288, 95% CI: 1.055-1.572, I(2) = 0%), but not in the NCEP-ATP III (OR = 1.351, 95% CI: 0.950-1.923, I(2) = 66.4%), Chinese (OR = 1.430, 95% CI: 0.891-2.294) and Japanese (OR = 1.542, 95% CI: 0.594-4.005, I(2) = 78.3%) subgroup. A certain degree of heterogeneity was observed among studies which cannot be explained by study design, diagnostic criteria and location. CONCLUSION: Our results demonstrated that SCH was significantly associated with a higher risk of MetS. Well-designed cohort studies were warranted to confirm our findings.

Metabolic syndrome and the risk of bone fractures: A Meta-analysis of prospective cohort studies.

Increasing evidence has suggested an association between metabolic syndrome (MetS) and bone fractures. However, because of controversial results it is still not clear whether this effect is protective or detrimental. Therefore, we conducted a meta-analysis of prospective studies to assess the association between them. Pertinent studies were identified by searching PubMed and EMBASE databases until the end of July 2015. Summary relative risks (RRs) and 95% confidence intervals (CIs) for associations between MetS and fracture risk were estimated with random effects models. Our meta-analysis included five prospective studies. The summarized RRs of any type of fractures for MetS were 0.76 (95%CI: 0.59-0.97, P = 0.026) with moderate heterogeneity (I(2) = 63.80%, P = 0.064). Notably, subgroup analyses by gender showed that significant inverse associations were observed only in men (summarized RR = 0.66; 95%CI = 0.51-0.86, P = 0.002; I(2) = 27.90%, P = 0.235; n = 5) but not in women (summarized RR = 0.96, 95%CI: 0.60-1.54, P = 0.866; I(2) = 83.40%, P = 0.002; n = 3). However, the difference of the pooled RRs from the two subgroups did not reach statistical significance with a test of interaction (p = 0.179 for the interaction test). When pooling the RRs of non-vertebral fractures, significant inverse associations were similarly observed in men (RR = 0.72, 95%CI: 0.52-0.99, P = 0.048) but not in women (RR = 0.99, 95%CI: 0.60-1.64, P = 0.969). There was no evidence of publication bias. Our findings demonstrated that MetS was significantly associated with a lower fracture risk. There might be gender differences in the relationship of MetS with fractures, but further confirmation is needed.

Glycogen synthase kinase-3 and p38 MAPK are required for opioid-induced microglia apoptosis.

Opioids have been widely applied in clinics as one of the most potent pain relievers for centuries, but their abuse has deleterious physiological effects beyond addiction. We previously reported that opioids inhibit cell growth and trigger apoptosis in lymphocytes. However, the underlying mechanism by which microglia apoptosis in response to opioids is not yet known. In this study, we show that morphine induces microglia apoptosis and caspase-3 activation in an opioid-receptor dependent manner. Morphine decreased the levels of microglia phosphorylated Akt (p-Akt) and p-GSK-3ß (glycogen synthase kinase-3 beta) in an opioid-receptor dependent manner. More interestingly, GSK-3ß inhibitor SB216763 significantly increases morphine-induced apoptosis in both BV-2 microglia and mouse primary microglial cells. Moreover, co-treatment of microglia with SB216763 and morphine led to a significant synergistic effect on the level of phospho-p38 mitogen-activated protein kinase (MAPK). In addition, inhibition of p38 MAPK by its specific inhibitor SB203580 significantly inhibited morphine-induced apoptosis and caspase-3 activation. Taken together, our data clearly demonstrates that morphine-induced apoptosis in microglial cells, which is mediated via GSK-3ß and p38 MAPK pathways.