The novel GLP-1/GIP dual agonist DA3-CH improves rat type 2 diabetes through activating AMPK/ACC signaling pathway.

BACKGROUND: Type 2 diabetes mellitus (T2DM) accounts for more than 95% of all diabetes. DA3-CH is a novel dual receptor agonist of glucagon like peptide-1 (GLP-1) and glucose dependent insulin stimulating polypeptide (GIP). The regulatory role of DA3-CH in T2DM has not been reported. METHODS: T2DM rat model was established successfully with high sugar and fat feed and streptomycin (STZ) induction. The mRNA and protein expression were measured with RT-PCR and western blotting. The apoptosis level in the pancreatic tissue was evaluated with Tunel staining. Blood glucose, fat, and oxidative stress indicators were measured. RESULTS: DA3-CH greatly improved T2DM symptoms by reducing blood glucose, blood fat, pancreatic tissue injury, apoptosis, and oxidative stress condition. The inactivation of Adenylate activated protein kinase (AMPK)/acetyl CoA carboxylase (ACC) signaling pathway in T2DM rats was promoted by DA3-CH. The influence of DA3-CH was significantly reversed by Com-C, the inhibitor of AMPK/ACC signaling pathway. CONCLUSIONS: DA3-CH might improve T2DM through targeting AMPK/ACC signaling pathway. This study might provide a novel therapeutic strategy for the prevention and treatment of T2DM through targeting DA3-CH and AMPK/ACC signaling pathway.

Effectiveness and safety of non-vitamin K antagonist oral anticoagulants in patients with hypertrophic cardiomyopathy with non-valvular atrial fibrillation.

Hypertrophic cardiomyopathy (HCM) patients with nonvalvular atrial fibrillation (AF) have an increased risk of suffering thromboembolic events. Vitamin K antagonists (VKA) are recommended as therapy but there is still limited data regarding the efficacy of prescribing non-vitamin K antagonist oral anticoagulants (NOACs). This retrospective study investigates the effectiveness and safety of NOAC administration in patients with HCM and AF. A total of 124 patients with HCM and AF on an oral anticoagulant therapy were recruited between January 2015 and December 2019; these patients were followed up until March 31, 2020. Kaplan-Meier analysis was used to compare the clinical outcomes in patients treated with NOACs versus warfarin. The Cox model was used to estimate the risk of clinically relevant bleeding. Our study included 124 patients, of which 48 (38.7%) received warfarin and 76 (61.3%) received NOACs. Survival analysis showed the patients undergoing NOACs had a lower risk of clinically relevant bleeding (log-rank P = 0.039) over a period of 53.6 months. The median time in therapeutic range (TTR) score was 50% (interquartile range: 40.43 to 57.08%). A total of nine patients (18.75%) had a good TTR with a median score of 66.35% (interquartile range: 64.58 to 77.75%). The incidence of death by all causes, cardiovascular death and thromboembolism were similar between NOAC and warfarin-treated patients (log-rank P = 0.239, log-rank P = 0.386, and log-rank P = 0.257, respectively). Patients treated with NOACs showed a significant reduction in the risk of clinical (P = 0.011) and gastrointestinal bleeding (P = 0.032). Cox multiple regression analysis showed age (HR 1.13, 95% CI 1.03-1.24; P = 0.013) and warfarin therapy (HR 7.37, 95% CI 1.63-33.36; P = 0.010) were independent predictors of clinically relevant bleeding. Compared to warfarin, NOACs were associated with a lower incidence of clinically relevant bleeding in HCM patients with AF, as demonstrated by the similar incidence of death by all causes, cardiovascular death and thromboembolic events.

[Expressions of ODF2 mRNA and protein are down-regulated in the sperm of asthenospermia patients].

OBJECTIVE: To investigate the mRNA and protein expressions of outer dense fiber 2 (ODF2) in the sperm of the asthenospermia patient and their differences from those in normal healthy men. METHODS: According to the WHO criteria, we collected semen samples from 45 asthenozoospermia patients and 15 normal healthy volunteers. Using computer-assisted sperm analysis (CASA), we divided the semen samples from the asthenospermia patients into a mild, a moderate and a severe group, and determined the mRNA and protein expressions of ODF2 in different groups by RT-PCR and Western blot. RESULTS: Compared with the normal healthy men, the expression of the ODF2 gene showed no statistically significant difference in the mild asthenospermia group (1.112 0 ± 0.525 5 vs 0.688 0 ± 0.372 0, P >0.05) but remarkably decreased in the moderate (0.483 3 ± 0.186 3, P <0.05) and severe asthenospermia patients (0.448 3 ± 0.340 8, P <0.01). The OD value (ODF2/ß-actin) of the ODF2 protein in the normal men exhibited no statistically significant difference from that in the mild asthenospermia group (0.458 7 ± 0.052 1 vs 0.326 1 ± 0.071 4, P >0.05), but markedly lower than in the moderate (0.145 4 ± 0.053 6, P <0.05) and severe asthenospermia patients (0.122 7 ± 0.045 7, P <0.01), which was consistent with the results of RT-PCR. CONCLUSIONS: Decreased mRNA and protein expressions of ODF2 in the sperm are positively correlated with declined sperm motility of the asthenospermia patient, which is suggestive of the involvement of the ODF2 gene in the regulation of sperm motility.