Investigating the mechanism and efficacy material basis of Xiehuo Xiaoying decoction for treating Graves' disease via thyroid cell apoptosis based on proteomics and molecular docking techniques.

ETHNOPHARMACOLOGICAL RELEVANCE: For numerous years, the Xiehuo Xiaoying decoction (XHXY), a traditional Chinese medicine formula, has demonstrated substantial promise in treating Graves' disease (GD) in clinical settings, showcasing significant potential. However, the therapeutic mechanism and efficacy material basis of XHXY remains obscure. AIM OF THE STUDY: This work aims to investigate the underlying mechanisms and to study the efficacy material basis of XHXY in anti-GD effect using a combination of TMT quantitative proteomics and molecular docking method. MATERIALS AND METHODS: GD model was initiated by administering Ad-TSH289. Subsequently, the mice underwent a four-week regimen that included oral gavage of XHXY at doses of 17 g/kg·d and 34 g/kg·d, along with intraperitoneal injections of Gentiopicroside (GPS). Utilizing the principles of pharmacological chemistry in traditional Chinese medicine, we employed high-performance liquid chromatography quadrupole time-of-flight mass spectrometry (HPLC-QTOF/MS) to discern prescribed prototype composition of XHXY in serum samples from mouse. TMT proteomics research provided evidence of XHXY's putative targets and important pathways in vivo. The binding activity of probable action targets and prototype composition was detected by molecular docking. Finally, Immunohistochemistry (IHC) and TUNEL staining were used to verify the mechanism of XHXY and GPS in anti-GD. RESULTS: XHXY and GPS alleviated GD by ameliorating the pathological changes and reducing thyroxine and TRAb levels. In mouse serum, a total of 31 prototypical XHXY ingredients were detected, and the majority of these components were from monarch and minister medicine. Proteomics study results indicated that the XHXY may mainly regulate targets including FAS-associated death domain protein (FADD), Apolipoprotein C-III, etc. and main pathways are Apoptosis, Cholesterol metabolism, TNF signalling pathway, etc. Strong binding activity of the prototypical active ingredient and GPS towards FADD, Caspase 8, and Caspase 3 was demonstrated by molecular docking. XHXY and its primary component, GPS, elevated the expression of FADD, Caspase 8, and Caspase 3, and enhance apoptosis in thyroid cells, as lastly validated by TUNEL and IHC staining. CONCLUSIONS: XHXY exhibits a favorable therapeutic effect in treating GD by promoting apoptosis in thyroid cells through the upregulation of FADD, Caspase 8, and Caspase 3 expression. And GPS is the main efficacy material basis for its therapeutic effect in anti-GD.

Association between serum 25-hydroxyvitamin D and diabetic kidney disease in Chinese patients with type 2 diabetes.

OBJECTIVE: The objective was to assess the association between 25-hydroxyvitamin D (25OHD) level and diabetic kidney disease (DKD) in Chinese patients with type 2 diabetes. METHODS: Data pertaining to 351 in-patients with type 2 diabetes were collected. Subjects were classified into three groups based on the level of urinary albumin-to-creatinine ratio (UACR). UACR < 30 mg/g was defined as normoalbuminuria, while UACR levels of 30-300 mg/g and ≥ 300 mg/g were defined as microalbuminuria and macroalbuminuria, respectively. Serum 25OHD and other clinical characteristics among various UACR groups were compared. The relationship between albuminuiria and 25OHD was analyzed. RESULTS: The prevalence of 25OHD insufficiency in the microalbuminuria group was significantly higher than that in the normoalbuminuria group (25.1% vs. 19.6%; P < 0.05); patients with macroalbuminuria had the highest prevalence of 25OHD deficiency (37.8%; P < 0.01 versus normoalbuminuria). Logistic regression analyses demonstrated that low 25OHD levels were associated with DKD [odds ratio (OR) = 1.51, 95% confidence interval (CI) 1.16-1.97). The association was more robust after adjusting for sex, hypertension, increased systolic blood pressure, glycemic status, and hyperuricemia (OR = 1.62, 95% CI 1.19-2.20). CONCLUSIONS: The prevalence of vitamin D insufficiency/deficiency in patients with albuminuria was overtly higher than that in patients without albuminuria among Chinese adults with type 2 diabetes. Vitamin D insufficiency/deficiency was independently associated with DKD in type 2 diabetes.

[Testosterone Undecanoate Pills improves insulin resistance in type-2 diabetes men with hypogonadism].

OBJECTIVE: To evaluate the effects of Testosterone Undecanoate Pills (TUP) on insulin resistance (IR) in type-2 diabetes men with hypogonadism. METHODS: We randomly divided 82 type-2 diabetes patients with hypogonadism into a treatment (n = 42) and a control group (n = 40), both maintaining their glucose- and lipid-reducing therapies, while the former treated orally with TUP in addition. After 6 months of medication, we compared the body mass index (BMI), waist circumference (WC), blood glucose level, HbA1c, lipid profile, IR index obtained by homeostatic model assessment (HOMA-IR), insulin sensitivity index (ISI), sex hormone levels, and sexual function scores between the two groups of patients. RESULTS: Compared with the baseline, the patients in the treatment group showed significant decreases after medication in BMI (ï¼»26.71 ± 2.39ï¼½ vs ï¼»25.15 ± 2.28ï¼½ kg/m2, P <0.05), WC (ï¼»89.96 ± 9.13ï¼½ vs ï¼»85.03 ± 9.58ï¼½ cm, P <0.05), HbA1C (ï¼»7.73 ± 1.31ï¼½ vs ï¼»7.01 ± 1.25ï¼½ %, P <0.05), and triglyeride (ï¼»1.97 ± 0.83ï¼½ vs ï¼»1.41 ± 0.69ï¼½ mmol/L, P <0.05), a markedly elevated level of total testosterone (ï¼»7.16 ± 2.21ï¼½ vs ï¼»14.22 ± 2.63ï¼½ nmol/L, P <0.05), and remarkable improvement in HOMA-IR (3.76 ± 1.18 vs 2.55 ± 1.03, P <0.05), ISI (96 ± 51 vs 138 ± 53, P <0.05) and total scores of the Aging Males' Symptoms (P <0.05). But no significant changes were observed in the scores of the International Index of Erectile Function (IIEF) after treatment (13.28 ± 6.38 vs 14.95 ± 6.08, P >0.05). CONCLUSIONS: TUP can significantly improve insulin resistance in type-2 diabetes men with hypogonadism.

Risk Factors for Hypogonadism in Male Patients with Type 2 Diabetes.

BACKGROUND: Male hypogonadism is an endocrine disease characterized by low levels of serum testosterone and is closely related to the development of diabetes. The purpose of the present study was to observe the risk factors for hypogonadism in male patients with type 2 diabetes. METHODS: A total of 213 patients with type 2 diabetes were enrolled and divided into a low total testosterone (TT) group (=75) and a normal TT group (=138). The patients' blood glucose, blood lipids, serum insulin, and sex hormones were measured. The correlations between the patients' metabolic index and sex hormone levels were analyzed. RESULTS: Compared with the normal TT group, body mass index (BMI), fasting insulin (FINS), and HOMA insulin resistance index (HOMA-IR) levels were significantly higher, but the luteinizing hormone (LH) levels were significantly lower in the low TT group (p < 0.05). Correlation analyses found that TT was negatively correlated with BMI, waist circumference (WC), FINS, and HOMA-IR. TT was positively correlated with LH and follicle-stimulating hormone (FSH). CONCLUSIONS: Several risk factors of diabetes associated closely with hypogonadism. BMI, metabolic syndrome (MS), HOMA-IR, and LH are independent risk factors for hypogonadism in male patients with type 2 diabetes.

Lithium Carbonate in the Treatment of Graves' Disease with ATD-Induced Hepatic Injury or Leukopenia.

Objective. GD with ATD-induced hepatic injury or leukopenia occurs frequently in clinical practice. The purpose of the present study was to observe the clinical effect of lithium carbonate on hyperthyroidism in patients with GD with hepatic injury or leukopenia. Methods. Fifty-one patients with GD with hepatic injury or leukopenia participated in the study. All patients were treated with lithium carbonate, in addition to hepatoprotective drugs or drugs that increase white blood cell count. Thyroid function, liver function, and white blood cells were measured. Clinical outcomes were observed after a 1-year follow-up. Results. After treatment for 36 weeks, symptoms of hyperthyroidism and the level of thyroid hormones were improved and liver function, and white blood cells returned to a normal level. Twelve patients (23.5%) obtained clinical remission, 6 patients (11.8%) relapsed after withdrawal, 25 patients (49.0%) received radioiodine therapy, and 8 patients (15.7%) underwent surgical procedures after lithium carbonate treatment. Conclusion. Lithium carbonate has effects on the treatment of mild-to-moderate hyperthyroidism caused by GD, and it is particularly suitable for patients with ATD-induced hepatic injury or leukopenia.