The association between subclinical hypothyroidism and metabolic syndrome: an update meta-analysis of observational studies.

The association between subclinical hypothyroidism (SCH) and metabolic syndrome (MetS) has been widely discussed. This study aimed to conduct an update and comprehensive meta-analysis to reveal the risk of MetS and its components in SCH. PubMed, Embase and ISI Web of Knowledge were searched to identify relevant studies through February 20th, 2020. Review Manager 5.3 and Stata 14.0 were used to conduct the meta-analysis. Both fixed-effects and random-effects models were used. In total, 18 articles (19 studies) incorporating 79,727 participants were included. The pooled OR for MetS comparing subjects with SCH with euthyroid subjects was 1.28 (95% CI: 1.19 to 1.39, p = 0.04, I2 = 40%). Subgroup analysis results showed significant associations of SCH and MetS in the adult subgroup (OR = 1.28, 95% CI: 1.18-1.40), Asian population subgroup (OR = 1.30, 95% CI: 1.19-1.42) and cross-sectional study design subgroup (OR = 1.31, 95% CI: 1.16-1.47). Significant associations of SCH and MetS also existed in all MetS definition criteria subgroups except the Chinese Diabetes Society (CDS) subgroup. SCH was correlated with MetS and was not affected by the subgroup analysis stratified by the proportion of females in the total population, the TSH cutoff value in SCH diagnostic criteria, or the adjustment for confounding factors. SCH was identified to be associated with an increased risk of obesity, hypertension, high triglyceride (TG) levels and low high-density lipoprotein cholesterol (HDL-C) levels. In conclusion, SCH is significantly associated with an increased risk of MetS and four out of five components of MetS.

Lower normal free thyroxine is associated with a higher risk of metabolic syndrome: a retrospective cohort on Chinese population.

BACKGROUND: Recently, the relationship between thyroid hormones (THs) across the euthyroid ranges and metabolic syndrome (MetS) has been widely discussed. This study aimed to present specific cutoff values of THs to assess the association between THs and MetS in a euthyroid cohort. METHODS: Data of 2694 subjects, aged 18-80 years, who attended health examination in Xi'an Electric Power Central Hospital from April 2011 to December 2015 were collected and analyzed. The first cohort enrolled 929 participants (followed up by 2221 person-years totally) to assess correlations between serum thyrotropin (TSH), triiodothyronine (T3), thyroxine (T4) levels and MetS. The second cohort included 698 participants (followed up by 1709 person-years totally) to evaluate relationships between serum free triiodothyronine (FT3), free thyroxine (FT4) levels and MetS. MetS was defined according to the criteria of the American Heart Association/National Heart, Lung, and Blood Institute (AHA/NHLBI) scientific statements of 2009. Euthyroidism was defined as serum TSH, FT3 and FT4 levels within the reference ranges without taking any thyroid medication. RESULTS: The cutoff values for TSH, T3, T4, FT3 and FT4 were 2.0mIU/L, 1.9 nmol/L, 117 nmol/L, 4.3 pmol/L and 16 pmol/L, respectively. Participants were categorized into two groups according to cutoff values: the lower-THs group and the higher-THs group. There was no significant difference in the risk of MetS between two groups in TSH, T3, T4 and FT3. The incidence of MetS was significantly higher in lower-FT4 group than higher-FT4 group (1.00 vs 0.622 (0.458, 0.846), P = 0.002). The lower-FT4/higher-TSH group had the highest hazard ratios of MetS. (2.131vs 1.0 (1.380,3.291), P = 0.006). CONCLUSIONS: Lower normal FT4 (FT4 ≤ 16.0 pmol/L) is an independent risk factor for MetS, and lower normal thyroid function (TSH > 2.0 mIU/L and FT4 ≤ 16.0 pmol/L) is associated with a higher risk of developing MetS.

Effect of Dihydrotestosterone on CostimulatoryMolecules in a Mouse Model of Graves' Disease.

Objective Graves' disease is the most common autoimmune thyroid disease and its prevalence and clinical manifestations are disparate between females and males. Costimulatory molecules play an essential role in regulating autoimmune responses. The objective of this study was to determine if expression of inhibitory molecules was correlated with treatment by dihydrotestosterone (DHT) in an in vivo BALB/c mouse model of experimental autoimmune Graves' disease.Methods Female BALB/c mice were immunized three times with thyroid stimulating hormone receptor A-subunit encoded by adenovirus to establish a Graves' disease model. Three different doses of DHT or a matching placebo were administered by implantation of slow-release pellets a week before the first immunization. Four weeks after the third immunization, the mice were euthanatized, and then the spleen and thymus were removed. Total thyroxine and free thyroxine levels in serum of mice were detected using a radioimmunoassay kit. Real-time polymerase chain reaction was performed to estimate the expression of costimulatory molecules in lymphocytes from the spleen and thymus. Flow cytometry was used to analyze the percentage of CD4+ T cells in splenic lymphocytes. Quantitative data were compared with unpaired t-tests. Correlation between two variables was analyzed using Analysis of Variance.Results Treatment with DHT can dramatically reduce total thyroxine and free thyroxine levels. Higher expression of programmed death-1 was found in the spleen of Graves' disease mice receiving 5 mg of DHT treatment (0.635±0.296 vs. 0.327±0.212; t=2.714, P=0.014), similarly, T-cell immunoglobulin domain and mucin domain 3 (TIM-3) in both the spleen (1.004±0.338 vs. 0.646±0.314; t=2.205, P=0.022) and the thymus (0.263±0.127 vs. 0.120±0.076; t=3.221, P=0.004) also increased after 5 mg of DHT treatment compared with the parallel placebo model mice. Moreover, the percentage of CD4+ T cells declined in the splenic lymphocytes of Graves' disease mice treated with 5 mg of DHT (19.90%±3.985% vs. 24.05%±2.587%; t=2.804, P=0.012). A significant negative association was observed between expression of TIM-3 in the spleen and serum levels of total thyroxine (r=-0.7106, P=0.014) as well as free thyroxine (r=-0.6542, P=0.029).Conclusion This study demonstrates that DHT can ameliorate experimental autoimmune Graves' disease, which may occur by up-regulating expression of programmed death-1 and TIM-3 and inhibiting development of CD4+ T cells.

miR-223 enhances the sensitivity of non-small cell lung cancer cells to erlotinib by targeting the insulin-like growth factor-1 receptor.

Lung cancer is the leading cause of cancer-related fatalities worldwide, and non-small cell lung cancer (NSCLC) is the main pathological type. MicroRNAs (miRNAs or miRs) are a class of small non-coding RNAs, which are involved in tumor initiation and progression. miR­223 is a tumor suppressor miRNA that has been reported in various types of cancer, including lung cancer. In the present study, to characterize the biological behavior of miR­223 in NSCLC, we established an miR­223 overexpression model in erlotinib-resistant PC­9 (PC­9/ER) cells by infection with lentivirus to induce the overexpression of miR­223. As a result, miR­223 enhanced the sensitivity of the PC­9/ER cells to erlotinib by inducing apoptosis in vitro. Additionally, in vivo experiments were performed using nude mice which were injected with the cancer cells [either the PC­9 (not resistant), PC­9/ER, or the PC­9/ER cells infected with miR­223)]. We found that the tumor volumes were reduced in the rats injected with the cells infected with miR­223. To further explore the underlying mechanisms, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis were used to identify the target molecules of miR­223. miR­223 was demonstrated to act as a local regulator of insulin-like growth factor-1 receptor (IGF-1R) in the acquired resistance to tyrosine kinase inhibitors (TKIs). Notably, the οverexpression of IGF-1R in NSCLC was downregulated by miR­223, and the activation of Akt/S6, the downstream pathway, was also inhibited. The inhibition of IGF-1R by miR­223 was attenuated by exogenous IGF-1 expression. Therefore, miR­223 may regulate the acquired resistance of PC­9/ER cells to erlotinib by targeting the IGF-1R/Akt/S6 signaling pathway. The overexpression of miR­223 may partially reverse the acquired resistance to epidermal growth factor receptor-TKIs, thus, providing a potential therapeutic strategy for TKI-resistant NSCLC.

[A Quercetin-Based Fluorescent Probe for the Recognition of Fluorid Ions].

Quercetin (Q) is one of the most common flavonoids present in roots, stems, leaves, flowers and fruits of most plants. In this study, a quercetin-based fluorescent probe for detecting fluorid ions had been proposed. With good selectivity and sensitivity for fluorid ions, Q-based fluorescent probe was easier to prepare, more eco-friendly and more innoxious compared with traditional fluorescent probe obtained by organic chemistry synthesis operation. There was a major fluorescence emission peak at 500 nm for Q in dimethyl sulfoxide (DMSO) when the excitation wavelength was 390 nm. The changes of fluorescence spectra were investigated before and after adding different anions into Q solution. The fluorescence emission intensity of Q even had no change when adding Cl-，Br-，I-，ClO-4，H2PO-4, respectively. While adding fluorid ions, the fluorescence emission intensity of Q was decreased obviously, which suggested fluorid ions could induce fluorescence quenching of Q in DMSO. And the fluorescence emission intensity of Q-F- system had almost no significant change when adding other anions (Cl-，Br-，I-，ClO-4，H2PO-4), which meant the progress for detecting fluorid ions didn't be affected by other anions, and Q showed a good selectivity for fluorid ions. The fluorescence titration spectra showed that the fluorescence emission intensity of Q was decreased with the increase of concentration of fluorid ions, and they were in concentration-dependent manner. The fluorescence titration curve exhibited that the Q as fluorescent probe can be applied to the quantification of fluorid ions with a good linearity (R2=0.991), linear range of 1.0～8.0×10-6 mol·L-1 and the detection limit of 1.0×10-7 mol·L-1. Not only the changes appeared in fluorescence spectra, but also the changes appeared in UV-visible spectra, compared with Q absorption spectrum, the location of band at 375 nm had no change after adding Cl-，Br-，I-，ClO-4，H2PO-4, respectively. However, when adding fluorid ions, the band at 375 nm was shifted to 394 nm, and the color of the solution was changed into dark yellow, which revealed the interactions between Q and fluorid ions. The probable mechanism of fluorid ions inducing fluorescence quenching of Q was obtained with 1H NMR spectrum and the changes of fluorescence emission intensity of Q-F- system in different polar solvents (DMSO containing different concentration of water). The interaction mode about Q and fluorid ions in DMSO was related with hydrogen bond. Both experiments suggested that the possible recognition mechanism on fluorid ions was: fluorid ions were destroyed or weakened by original hydrogen bonds, and were promoted charge transfer within quercetin molecule, which resulted in fluorescence intensity decreasing of quercetin. This method was successfully applied in detecting fluorid ions of samples in DMSO with good recovery.

Chemical composition, antimicrobial property and microencapsulation of Mustard (Sinapis alba) seed essential oil by complex coacervation.

In this study, the essential oil from mustard seed was isolated by simultaneous steam distillation and extraction (SDE) and analyzed by gas chromatography-mass spectrometry (GC-MS). Fourteen components were identified in the mustard seed essential oil with allyl isothiocyanate being the main component (71.06%). The essential oil has a broad-spectrum antimicrobial activity with inhibition zones and MIC values in the range of 9.68-15.57 mm and 128-512 µg/mL respectively. The essential oil was subsequently encapsulated in complex coacervation microcapsules with genipin, a natural water-soluble cross-linker. The optimum parameters for the hardening effectiveness of the genipin-hardened essential oil microcapsules were 8h at 40°C and pH 10.0 with a genipin concentration of 0.075 g/g gelatin. The genipin-hardened microcapsules had a particle size of mainly 5-10 µm and strong chemistry stability which is potential for its application in food preservation.

[A comparison study on clinical chromatographic fingerprintings of mycolic acids analysis of 18 standard strains of Mycobacteria in China].

OBJECTIVE: A clinical chromatographic fingerprinting of 18 standard strains of Mycobacteria commercialized in China by high-performance liquid chromatography approach was developed and improved in this laboratory. A comparison of clinical chromatographic fingerprintings of mycolic acids was carried out. METHODS: Mycolic acids were extracted from whole cultured cells of Mycobacteria by biochemical methods, and then samples was prepared for analysis after the mycolic acids were saponified, acidified and derived. The samples were detected by high-performance liquid chromatography under optimum conditions. RESULTS: Using above techniques a clinical chromatographic fingerprinting of Mycolic acids analysis was successfully established. The repeatability of the mycolic acids fingerprinting was evaluated. Coefficient of variation (CV) of chromatographic fingerprinting was between 0.20% - 0.83%. CONCLUSIONS: The first clinical chromatographic fingerprinting of 18 standard strains of Mycobacteria in China was established in this laboratory. Mycobacteria can be accurately identified according to chromatographic fingerprinting in a short time. Moreover, there was significant difference between BCG vaccine and Mycobacterium bovis when their peak was compared, which may lead to research of new tools for identifying insidious infection of tuberculosis and for the study of the mechanism of drug tolerance.