Targeting the chromatin structural changes of antitumor immunity.

Epigenomic imbalance drives abnormal transcriptional processes, promoting the onset and progression of cancer. Although defective gene regulation generally affects carcinogenesis and tumor suppression networks, tumor immunogenicity and immune cells involved in antitumor responses may also be affected by epigenomic changes, which may have significant implications for the development and application of epigenetic therapy, cancer immunotherapy, and their combinations. Herein, we focus on the impact of epigenetic regulation on tumor immune cell function and the role of key abnormal epigenetic processes, DNA methylation, histone post-translational modification, and chromatin structure in tumor immunogenicity, and introduce these epigenetic research methods. We emphasize the value of small-molecule inhibitors of epigenetic modulators in enhancing antitumor immune responses and discuss the challenges of developing treatment plans that combine epigenetic therapy and immunotherapy through the complex interaction between cancer epigenetics and cancer immunology.

Endothelial Function in Patients with Subclinical Hypothyroidism: A Meta-Analysis.

The purpose of this meta-analysis was to determine whether patients with subclinical hypothyroidism (SCH) have impaired endothelial function, which is assessed by carotid intima-media thickness (C-IMT) and flow-mediated dilatation (FMD) of brachial artery. PubMed, Embase and Cochrane Library databases and the key studies references were searched in our study, prior to July 2017 for all language articles about FMD or C-IMT in SCH and euthyroid subjects. Two authors screened documents and extracted data by pre-established standard independently. The pooled estimate for continuous data was calculated using random-effects models. Statistical heterogeneity was evaluated using I2 statistics. Subgroup analyses were conducted to assess the robustness of the meta-analysis. Publication bias was examined with funnel plot analysis and Egger's test. In this meta-analysis, 10 studies with 760 subjects are related to FMD with SCH and 23 studies with 1521 subjects are related to C-IMT with SCH. The pooled estimate of the weighted mean difference (WMD) has revealed that SCH correlated with increased C-IMT [WMD 0.069 mm; 95% CI (0.042, 0.095); p<0.001] and decreased FMD [WMD -1.848%; 95% CI (-2.298, -1.399); p<0.001] with high heterogeneity.: Compared with EU controls, SCH was also associated with an increased diastolic blood pressure (DBP), systolic blood pressure (SBP), triglyceride (TG), total cholesterol (TC) levels, and low density lipoprotein cholesterol (LDL-C). This meta-analysis demonstrates that SCH is associated with endothelial dysfunction, which may relate with increased thyroid-stimulating hormone (TSH). Hypertension and dyslipidemia may play a crucial part in the development of endothelial dysfunction.

The Change of Left Ventricular Function in Rats with Subclinical Hypothyroid and the Effects of Thyroxine Replacement.

OBJECTIVE: The main purpose of this study was to explore the relationships between serca2a, Ryr2, adipokines, and the left ventricular function in the subclinical hypothyroidism with different TSH levels and to determine the impact of L-T4 treatment on these indexes. METHODS: Sixty-five male Wistar rats were randomly divided into five groups: control group; sHT A, B, and C group; and sHT + T4 group. The sHT rats were induced by methimazole (MMI), and the sHT + T4 rats were administered with L-T4 treatment after 8 weeks of MMI administration. Serum TT4, TSH, APN, chemerin, and TNF-α were detected by radioimmunoassay kits and ELISA kits; left ventricular function was measured by PowerLab system via subclavian artery catheter. The expression of Serca2a, Ryr2, APN, chemerin, and TNF-α were detected by RT-PCR, Western blot, and immunohistochemistry. RESULTS: The sHT groups had significantly higher TSH, chemerin, and TNF-α and lower Serca2a, Ryr2, and APN. The left ventricular pressure and heart rate in sHT groups were significantly lower in control and sHT + T4 group. Histopathological examination revealed the pathological changes in the sHT rats' heart. L-T4 administration reduced TSH level and improved left ventricular function. CONCLUSIONS: TSH can impair left ventricular function by regulating several factors, and L-T4 treatment ameliorates it in sHT rats.

Adipokine expression and endothelial function in subclinical hypothyroidism rats.

The purpose of our study was to observe adipokine expression and endothelial function in subclinical hypothyroidism (sHT) rats and to determine whether levothyroxine (LT4) treatment affects these changes. Sixty-five male Wistar rats were randomly divided into five groups: the control group; sHT A, B and C groups and the sHT + T4 group. The sHT rats were induced by methimazole (MMI) and the sHT + T4 rats were administered LT4 treatment after 8 weeks of MMI administration. Thyroid function and lipid levels were measured using radioimmunoassays and enzymatic colorimetric methods, respectively. Serum adiponectin (APN), chemerin, TNF-α, endothelin (ET-1) and nitric oxide (NO) levels were measured using ELISA kits and a nitric-reductive assay. The expression of APN, chemerin and TNF-α in visceral adipose tissue (VAT) was measured in experimental rats using RT-PCR and Western blotting. Hematoxylin-eosin (HE) staining was used to observe changes in adipose tissue. The sHT rats had significantly higher levels of thyroid-stimulating hormone (TSH), TNF-α, chemerin, ET-1, total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) and lower levels of APN and NO than those in control and sHT + T4 rats. Based on Pearson correlation analysis, the levels of chemerin, TNF-α, ET-1, LDL-C, TC and triglyceride (TG) were positively correlated with TSH, but APN and NO levels were negatively correlated with TSH. These findings demonstrated that high TSH levels contribute to the changes of adipokines and endothelial dysfunction in sHT, but LT4 treatment ameliorates those changes.