Association of thyroid autoimmunity with the presence and severity of coronary atherosclerosis in patients undergoing coronary angiography.

Studies on the association of thyroid autoimmunity with cardiometabolic risk and coronary artery disease (CAD) have produced conflicting results. This study aimed to investigate the relationship of thyroid autoimmune bodies (thyroid peroxidase antibody [TPOAb] and thyroglobulin antibody [TgAb]) with CAD in euthyroid subjects undergoing coronary angiography. A total of 307 subjects who underwent coronary angiography were included. The severity of coronary atherosclerosis was evaluated by using Gensini score. Serum TSH, total T3, total T4, TPOAb, TgAb, lipid levels et al were measured and compared between the groups with and without CAD. Logistic multivariate regression analysis were performed to assess the associations. Levels of thyroid hormones were comparable between the two groups. The positive percentage of anti-Tg antibodies was higher in non-CAD group (15.22% vs 7.91%, χ2 = 3.95, p = .047) while no significant difference was observed for anti-TPO antibodies (19.57% vs 17.21%, χ2 = 0.243, p = .622). The natural log-transformed Gensini score (ln (Gensini score)) was lower in the TgAb+ group (2.94 ± 1.11 vs 2.41 ± 1.18, P = .015). There was no significant difference for ln (Gensini score) between TPOAb- and TPOAb+ group (2.90 ± 1.14 vs 2.85 ± 1.09, P = .782). Logistical regression analysis revealed that positive TgAb was inversely associated with the presence of CAD (OR: 0.387, 95% CI: 0.157-0.952, p = .039) independent of other risk factors. The results showed that TgAb positivity might be an independent protective factor for CAD.

Long noncoding RNA NONHSAT177112.1 aggravates inflammation and apoptosis in LPS-treated human cardiomyocytes.

Aim: To explore the roles of lncRNA NONHSAT177112.1 in the inflammatory injury of human cardiomyocytes (HCMs) induced by lipopolysaccharide (LPS). Materials & methods: The sublocalization of NONHSAT177112.1 was detected by FISH. HCMs were stimulated with LPS to induce inflammatory injury. NONHSAT177112.1 expression was detected by quantitative real-time PCR. Cell apoptosis and viability were detected by flow cytometry and CCK-8 assays. The expression of inflammatory cytokines and myocardial enzymes were detected by PCR and ELISA. Results: NONHSAT177112.1 is expressed in the nucleus and cytoplasm. NONHSAT177112.1 showed dynamic expression that first increased and then decreased during LPS stimulation. NONHSAT177112.1 knockdown reversed the promotion effect of LPS on inflammatory injury. Conversely, NONHSAT177112.1 overexpression exerted the opposite effects. Conclusion: NONHSAT177112.1 aggravates inflammatory injury in LPS-treated HCMs.

Propofol suppresses cell viability, cell cycle progression and motility and induces cell apoptosis of ovarian cancer cells through suppressing MEK/ERK signaling via targeting circVPS13C/miR-145 axis.

BACKGROUND: Propofol is a kind of common intravenous anaesthetic agent that plays an anti-tumor role in a variety of cancers, including ovarian cancer. However, the working mechanism of Propofol in ovarian cancer needs further exploration. METHODS: The viability and metastasis of ovarian cancer cells were assessed by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and transwell assays. Flow cytometry was used to evaluate the cell cycle and apoptosis. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to examine the abundance of circular RNA vacuolar protein sorting 13 homolog C (circVPS13C) and microRNA-145 (miR-145). The target relationship between miR-145 and circVPS13C was predicted by circinteractome database and verified by dual-luciferase reporter assay, RNA-binding protein immunoprecipitation (RIP) assay and RNA-pull down assay. Western blot assay was used to detect the levels of phosphorylated extracellular regulated MAP kinase (p-ERK), ERK, p-MAP kinse-ERK kinase (p-MEK) and MEK, in ovarian cancer cells. RESULTS: Propofol treatment suppressed the viability, cell cycle and motility and elevated the apoptosis rate of ovarian cancer cells. Propofol up-regulated miR-145 in a dose-dependent manner. Propofol exerted an anti-tumor role partly through up-regulating miR-145. MiR-145 was a direct target of circVPS13C. Propofol suppressed the progression of ovarian cancer through up-regulating miR-145 via suppressing circVPS13C. Propofol functioned through circVPS13C/miR-145/MEK/ERK signaling in ovarian cancer cells. CONCLUSION: Propofol suppressed the proliferation, cell cycle, migration and invasion and induced the apoptosis of ovarian cancer cells through circVPS13C/miR-145/MEK/ERK signaling in vitro.

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.

Irisin protects macrophages from oxidized low density lipoprotein-induced apoptosis by inhibiting the endoplasmic reticulum stress pathway.

Irisin is a newly discovered myokine which can relieve metabolic disorders and resist atherosclerosis. The effects of irisin on ox-LDL-induced macrophage apoptosis and endoplasmic reticulum stress-related pathways were observed in vitro. RAW264.7 macrophages were cultured in vitro and pretreated with irisin at 20, 40 and 80 ng/ml for 30 min, followed by culture with 100 mg/L ox-LDL and 5 mg/L tunicamycin (TM) for 12 h. The cell viability and apoptosis were detected by MTT assay and annexin V-FITC double staining. The nuclear translocation of activating transcription factor 6 (ATF6) was detected by immunofluorescence assay. Western blot was used to detect the expressions of p-PERK, p-eIF2α, C/EBP homologous protein (CHOP) and Bcl-2. Irisin reduced lipid accumulation in macrophages in a concentration-dependent pattern and significantly inhibited apoptosis induced by ox-LDL and TM. Compared with ox-LDL and TM groups, the expressions of CHOP, p-PERK and p-eIF2α in the irisin group significantly decreased, the translocation of ATF6 from cytoplasm to nucleus was significantly weakened, and Bcl-2 expression significantly increased. Irisin can alleviate the apoptosis of macrophages induced by ox-LDL, which may be achieved by inhibiting the PERK/eIF2α/CHOP and ATF6/CHOP endoplasmic reticulum stress signaling pathways.

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.

Resveratrol raises in vitro anticancer effects of paclitaxel in NSCLC cell line A549 through COX-2 expression.

The aim of this study was to determine the raising anticancer effects of resveratrol (Res) on paclitaxel (PA) in non-small cell lung cancer (NSCLC) cell line A549. The 10 µg/ml of Res had no effect on human fetal lung fibroblast MRC-5 cells or on A549 cancer cells and the 5 or 10 µg/ml of PA also had no effect on MRC-5 normal cells. PA-L (5 µg/ml) and PA-H (10 µg/ml) had the growth inhibitory effects in NSCLC cell line A549, and Res increased these growth inhibitory effects. By flow cytometry experiment, after Res (5 µg/ml)+PA-H (10 µg/ml) treatment, the A549 cells showed the most apoptosic cells compared to other group treatments, and after additional treatment with Res, the apoptosic cells of both two PA concentrations were raised. Res+PA could reduce the mRNA and protein expressions of COX-2, and Res+PA could reduce the COX-2 related genes of VEGF, MMP-1, MMP-2, MMP-9, NF-κB, Bcl-2, Bcl-xL, procollagen I, collagen I, collagen III and CTGF, TNF-α, IL-1ß, iNOS and raise the TIMP-1, TIMP-2, TIMP-3, IκB-α, p53, p21, caspase-3, caspase-8, caspase-9, Bax genes compared to the control cells and the PA treated cells. From these results, it can be suggested that Res could raise the anticancer effects of PA in A549 cells, thus Res might be used as a good sensitizing agent for PA.