Selective Activation of G Protein-Coupled Estrogen Receptor 1 (GPER1) Reduces ER Stress and Pyroptosis via AMPK Signaling Pathway in Experimental Subarachnoid Hemorrhage.

Neuroinflammation is a critical pathogenic event following hemorrhagic stroke. Endoplasmic reticulum (ER) stress-induced apoptosis and nucleotide-binding domain, leucine-rich repeat, and pyrin domain-containing protein 3(NLRP3)-associated pyroptosis can contribute to the escalation of neuroinflammatory responses, leading to increased brain damage. G protein-coupled estrogen receptor 1(GPER1), as the most extensively characterized brain-derived estrogen, was reported to trigger neuroprotective effects. However, the anti-apoptotic and anti-pyroptotic effect of GPER1 activation and the underlying mechanism has not been fully elucidated. We established the experimental SAH model by intravascular perforation. The GPER1 selective agonist G1 was intravenously administered 1 h following SAH. For mechanistic exploration, the selective inhibitor of adenosine monophosphate-activated protein kinase (AMPK), dorsomorphin, was administered via intracerebroventricular injection 30 min prior to SAH induction. Post-SAH assessments included SAH grade, the short-term and long-term neurological outcomes, brain edema, cerebral blood flow, transmission electron microscopy (TEM), western blot (WB), ELISA, TUNEL staining, Fluoro-Jade C staining (FJC), and immunofluorescence staining. The expression of GPER1 was observed to elevate at 6 h and peaked at 24 h subsequent to SAH, predominantly co-localized with neurons. Post-treatment with G1 markedly ameliorated both the short-term and long-term neurological deficits of SAH mouse, as well as inhibiting the expression of neuronal ER stress-associated apoptotic proteins (i.e., CHOP, GRP78, Caspase-12, Cleaved Caspase-3, Bax, Bcl2) and pyroptosis-associated proteins (i.e., NLRP3, ASC, Cleaved Caspase-1). Additionally, our research revealed that inhibition of AMPK with dorsomorphin attenuated the neuroprotective effects of G1. This was accompanied by modifications in the molecular pathways associated with ER stress-induced apoptosis and pyroptosis. These data herein elucidated that GPER1 exerted neuroprotective effects by mitigating neuroinflammation in an AMPK-dependent manner, which modulates neuronal ER stress-associated apoptosis and pyroptosis. Boosting the anti-apoptotic and anti-pyroptotic effect by activating GPER1 may be an efficient treatment strategy for SAH patients.

The impact of telehealth education on self-management in patients with coexisting type 2 diabetes mellitus and hypertension: a 26-week randomized controlled trial.

BACKGROUND: The prevalence of coexisting type 2 diabetes mellitus and hypertension is increasing globally and posing significant health challenges. Effective self-management is crucial for controlling the disease and preventing complications. Telehealth education has emerged as a promising approach to enhancing self-management. OBJECTIVE: This study aimed to investigate the effects of telehealth education on glycolipid metabolism, blood pressure, and self-management in patients with coexisting type 2 diabetes mellitus and hypertension. METHODS: This study included 174 patients diagnosed with type 2 diabetes and hypertension from October 2022 to March 2023 at the 900th Hospital of the Joint Logistic Support Force of the Chinese People's Liberation Army. The patients were randomly assigned to the control group or the telehealth education group. The control group received conventional diabetes education including diet and exercise guidance, while the telehealth education group received additional online education through the WeChatapplication. Both groups were followed up for 26 weeks and the changes in glycolipid metabolism, blood pressure, and self-management were compared between the groups. RESULTS: After 26 weeks of intervention, the telehealth education group showed statistically significant reductions in weight, body mass index, fasting blood glucose, 2 h postprandial blood glucose, and hemoglobin A1c compared to the control group (P < 0.05). The telehealth education group also exhibited a significant decrease in systolic blood pressure and low-density lipoprotein-C level (P < 0.05). The Summary of Diabetes Self-Care Activities score, which reflects the level of diabetes self-management, demonstrated that the telehealth education group had a significantly better total score as well as superior scores in all five sub-categories (diet, blood glucose testing, medication use, and foot care) compared to the control group (P < 0.05). CONCLUSION: Our findings confirmed that telehealth education effectively enhanced the self-management capabilities of patients with coexisting type 2 diabetes and hypertension, leading to better glycolipid and blood pressure control. The use of telehealth education may potentially improve the interaction between medical staff and patients in the management of chronic diseases.

Research Landscape of Physiologically Based Pharmacokinetic Model Utilization in Different Fields: A Bibliometric Analysis (1999-2023).

PURPOSE: The physiologically based pharmacokinetic (PBPK) modeling has received increasing attention owing to its excellent predictive abilities. However, there has been no bibliometric analysis about PBPK modeling. This research aimed to summarize the research development and hot points in PBPK model utilization overall through bibliometric analysis. METHODS: We searched for publications related to the PBPK modeling from 1999 to 2023 in the Web of Science Core Collection (WoSCC) database. The Microsoft Office Excel, CiteSpace and VOSviewers were used to perform the analyses. RESULTS: A total of 4,649 records from 1999 to 2023 were identified, and the largest number of publications focused in the period 2018-2023. The United States was the leading country, and the Environmental Protection Agency (EPA) was the leading institution. The journal Drug Metabolism and Disposition published and co-cited the most articles. Drug-drug interactions, special populations, and new drug development are the main topics in this research field. CONCLUSION: We first visualize the research landscape and hotspots of the PBPK modeling through bibliometric methods. Our study provides a better understanding for researchers, especially beginners about the dynamization of PBPK modeling and presents the relevant trend in the future.

Glucagon-like peptide-1 receptor agonist liraglutide therapy for psoriasis patients with type 2 diabetes: a randomized-controlled trial.

OBJECTIVE: There were some clinical studies on GLP-1R agonist liraglutide therapy for psoriasis patients with type 2 diabetes, but there is a lack of randomized controlled trials and the mechanism of which remains unclear. METHOD: A total of 25 psoriasis patients with type 2 diabetes were randomized 1: 1 divided into the control group (n = 13) or liraglutide group (n = 12) for 12 weeks. We determined the PASI, the DLQI, histopathology of psoriasis skin, and the expression of IL-17, IL-23, and TNF-α in the psoriasis skin. RESULTS: After 12 weeks of treatment, the mean DLQI of the treatment group decreased from 22.00 ± 5.85 to 3.82 ± 3.60 (p < .05). Compared to week 12, the change in the baseline value of PASI and DLQI in the treatment group showed a significant difference compared with the control group (p < .05). The pathological changes of psoriasis skin and the expression of IL-17, IL-23, TNF-α in the psoriasis skin were improved in the treatment group. No serious adverse events occurred. CONCLUSION: The skin lesions in psoriasis patients with type 2 diabetes were significantly improved after treatment with liraglutide, which may be related to the inhibition of the expression of inflammatory factors such as IL-23, IL-17, and TNF-α.