Dulaglutide restores endothelial progenitor cell levels in diabetic mice and mitigates high glucose-induced endothelial injury through SIRT1-mediated mitochondrial fission.

Type 2 diabetes mellitus (T2DM) significantly impairs the functionality and number of endothelial progenitor cells (EPCs) and resident endothelial cells, critical for vascular repair and regeneration, exacerbating the risk of vascular complications. GLP-1 receptor agonists, like dulaglutide, have emerged as promising therapeutic agents due to their multifaceted effects, including the enhancement of EPC activity and protection of endothelial cells. This study investigates dulaglutide's effects on peripheral blood levels of CD34+ and CD133+ cells in a mouse model of lower limb ischemia and its protective mechanisms against high-glucose-induced damage in endothelial cells. Results demonstrated that dulaglutide significantly improves blood flow, reduces tissue damage and inflammation in ischemic limbs, and enhances glycemic control. Furthermore, dulaglutide alleviated high-glucose-induced endothelial cell damage, evident from improved tube formation, reduced reactive oxygen species accumulation, and restored endothelial junction integrity. Mechanistically, dulaglutide mitigated mitochondrial fission in endothelial cells under high-glucose conditions, partly through maintaining SIRT1 expression, which is crucial for mitochondrial dynamics. This study reveals the potential of dulaglutide as a therapeutic option for vascular complications in T2DM patients, highlighting its role in improving endothelial function and mitochondrial integrity.

Prevalence of hyperthyroidism with hypercalcemia in Xindu district and the efficacy of vitamin D3 treatment in these patients: a randomized trial.

BACKGROUND: This trial aimed to analyze the relationship between hyperthyroidism and the morbidity rate of hypercalcemia in the Xindu district, Chengdu, Sichuan province. We observed the level of serum calcium, the bone metabolic and thyroid autoimmune-related antibodies index during vitamin D3 treatment combined with traditional antithyroid drugs (ATD). METHODS: Our research included hyperthyroid patients with a first-time diagnosis of Graves diseases (GD) combined with hypercalcemia on the basis of conventional anti-hyperthyroidism therapy, which were randomized into a vitamin D3 group (vitamin D3, 800-1,200 IU/day) and an ATD group (methimazole, 15-30 mg/day). All hyperthyroidism patients with hypercalcemia were analyzed, and changes in serum calcium (Ca2+), parathyroid hormone (PTH), thyroid function, thyroid autoimmune-related antibodies, and 25-dihydroxyvitamin D (25-OHVit D) levels during treatment of thyrotoxicosis with added vitamin D3 were explored. RESULTS: In total, 184 patients with hyperthyroidism were observed, including 36 (19.57%) patients associated with hypercalcemia, with an age of onset of (56.39±5.80) years old. Twelve (6.52%) of these 36 cases reported digestive symptoms as the first manifestation, and four (2.17%) patients presented with a hypercalcemia crisis as the first manifestation. Serum Ca2+, free triiodothyronine (FT3), free thyroxine (FT4), and thyrotropin hormone receptor antibody (TRAb) levels increased in patients with hypercalcemia. Following the addition of vitamin D3 treatment, serum Ca2+, FT3, FT4, and TRAb levels were significantly decreased relative to the ATD group, while the thyroid-stimulating hormone (TSH), PTH, and 25-OHVit D levels were normalized. CONCLUSIONS: Our study highlighted the importance of taking functional digestive disturbance into consideration in hyperthyroidism diagnosis, even in the absence of the typical symptoms. The level of thyroid related antibodies, thyroid function, and bone metabolism in hyperthyroidism patients combined with hypercalcemia could be improved by vitamin D3 adjuvant therapy. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR2100047870.

Abnormalities of the PRMT1-ADMA-DDAH1 metabolism axis and probucol treatment in diabetic patients and diabetic rats.

BACKGROUND: Symmetrical dimethylarginine (ADMA) endogenously inhibits nitric oxide synthase (NOS) and strongly indicates oxidant stress, whose formation primarily derived from type 1 protein arginine N-methyltransferase (PRMT1) and whose metabolism was governed by type 1 dimethylarginine dimethylaminohydrolase (DDAH1). This study aimed to evaluate participation of the PRMT1-ADMA-DDAH1 metabolism axis in the kidneys of type 2 diabetes model rats and human subjects, and the effect of probucol on this axis and renal function. METHODS: A total of 30 rats were randomly assigned to a normal group (NC, n=10), diabetic group (DM, n=10), and a diabetics under probucol treatment group (PM, n=10). Throughout 8 weeks of probucol treatment, plasma NOS, the malondialdehyde (MDA), superoxide dismutase (SOD), nitric oxide (NO), and catalase (CAT) activity were evaluated by chemical colorimetric approach. ADMA concentration was evaluated with an enzyme-linked immunosorbent assay (ELISA) and analysis of expression of PRMT1 and DDAH1 in kidneys with reverse transcription-polymerase chain reaction (RT-PCR), immunohistochemistry (IHC) and western blotting were performed. RESULTS: The expression of DDAH1 in the kidney, and the plasma NOS, NO, SOD, and CAT activities in diabetic group were lower, while MDA and the expression of PRMT1 and ADMA were higher in contrast to the control group. In diabetics rats receiving probucol, the expressions of DDAH1 and ADMA were downregulated, whereas that of PRMT1 was upregulated. Probucol inhibited the indexes of oxidative stress and improved the kidney function in both diabetic rats and humans. CONCLUSIONS: We found that the expression of the PRMT1-ADMA-DDAH1 axis was altered in the kidneys of diabetic rats. Moreover, results indicated that probucol therapy regulates expression at both ends of this axis, which may preserve renal function by reducing oxidant stress. Therefore, probucol may partially restore expression of the PRMT1-ADMA-DDAH1 axis in diabetic kidneys, immigrate oxidant stress, and enhance renal function.

Anti-obesity effect of Lactobacillus plantarum CQPC01 by modulating lipid metabolism in high-fat diet-induced C57BL/6 mice.

Lactic acid bacteria (LAB) are an important group of microorganisms in the food industry. LAB with health benefits are considered natural elements promoting consumer health. The study investigated the anti-obesity effects of Lactobacillus plantarum CQPC01 (LP-CQPC01) on high-fat diet-induced mice. Liver morphology, liver function indexes, lipid indexes, and inflammatory factors in the serum and liver were determined. Expressions of lipid metabolism-related gene were also detected by qPCR. LP-CQPC01 slowed the HFD-induced increase in body weight, decreased the organ indexes, alleviated hepatic lipid accumulation, and inhibited the increased adipose cell volume. LP-CQPC01 decreased lipid levels of serum and liver, and the contents of pro-inflammatory factors, and increased the IL-4 and IL-10 contents. LP-CQPC01 downregulated the expressions of the C/EBP-α and PPARγ mRNA and upregulated CYP7A1, CPT1, LPL, CAT, SOD1, and SOD2 mRNA. Our results indicated that LP-CQPC01 is a potential probiotic for preventing or alleviating high-energy intake-related lipid conditions. PRACTICAL APPLICATIONS: Obesity is a factor of a variety of cardiovascular diseases. Therefore, it is necessary to suppress the occurrence of fat accumulation in time. This study investigated the effect of LP-CQPC01 on lipid regulation in mice fed a high-fat diet (HFD) and clarified the mechanism of strain to alleviate obesity by enhancing the decomposition of cholesterol and detoxification of fat. LP-CQPC01 reduced fat accumulation without oxidative damage, and was confirmed by the attenuated pathological changes of liver. This research can serve as a significant reference for future research, prevention, and treatment of high-energy intake-related lipid conditions, and the development of functional foods with anti-obesity activity.

Anti-thyroid drug-induced lupus: a case report and review of the literature

We report a case of drug-induced lupus (DIL) on a Chinese woman caused by methimazole (MMI). This report discusses DIL associated with MMI and briefly reviewed the literature concerning to anti-thyroid DIL.

Anti-thyroid drug-induced lupus: a case report and review of the literature.

We report a case of drug-induced lupus (DIL) on a Chinese woman caused by methimazole (MMI). This report discusses DIL associated with MMI and briefly reviewed the literature concerning to anti-thyroid DIL.

A surgeon led smoking cessation intervention in a head and neck cancer centre.

BACKGROUND: The government has recognised the role of healthcare professionals in smoking cessation interventions with integrated care pathways for identification and referral of at-risk patients who smoke. Referral for suspected cancers has been suggested as a 'teachable moment', whereby individuals are motivated and more likely to adopt risk-reducing behaviours. A head and neck cancer referral clinic could therefore provide opportunities for smoking cessation intervention. This study aims to pilot a brief smoking cessation intervention during a consultation visit for patients referred with suspected head and neck cancer and evaluate its acceptability and impact. METHODS: A brief script for smoking cessation intervention which included a smoking cessation referral was designed to be delivered to patients attending a rapid access clinic. Patient outcome data was collected by the stop smoking team for patients who accepted the referral. A subset of these patients was also interviewed by telephone; these findings were combined with data provided by the stop smoking services to assess the acceptability and impact of pilot smoking cessation intervention on patients. RESULTS: In total, 473 new patients attended the clinic during the study period, of whom 102 (22%) were smokers. Of these, 80 (78%) accepted a referral to stop smoking services. A total of 75 (74%) patients were approached subsequently in a telephone survey. Of the 80 newly referred patients, 29 (36%) quit smoking at least temporarily. Another eight patients reduced their smoking or set a quit date (10%), so the experience of attending the clinic and the intervention impacted favourably on almost half of the patients (46%). The patient survey found the intervention to be acceptable for 94% (n = 50) of patients. Qualitative analysis of patient responses revealed five elements which support the acceptability of the intervention. CONCLUSIONS: The findings of this pilot study suggest that discussion of smoking cessation with patients referred for suspected head and neck cancer may have an impact and facilitate the process towards quitting. A possible diagnosis of cancer appears to present a 'teachable moment' to encourage positive health behaviour change.