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Objective: We aimed to investigate the role of forkhead box O1 (FoxO1) inhibitor AS1842856 (AS) in nonalcoholic steatohepatitis (NASH) mice and the potential mechanisms. Methods: Mice were given methionine‐choline‐sufficient (MCS), or methionine‐ and choline‐deficient (MCD) diet for 5 weeks, along with AS (60 mg/kg) or vehicle gavage treatment (0.2 mL/day). Body and liver weight, serum triglyceride (TG), low‐density lipoprotein‐cholesterol (LDL‐C), high‐density lipoprotein‐cholesterol (HDL‐C), alanine aminotransferase (ALT), aspartate aminotransferase (AST), fasting glucose and insulin levels were measured. Liver macrophage infiltration and ileal ZO‐1 protein expression were also detected. Interleukin (IL)‐6, IL‐1β, and tumor necrosis factor (TNF)‐α, sterol regulatory element binding protein (SREBP)‐1c, phosphoenolpyruvate carboxykinase (PEPCK), and glucose‐6‐phosphatase (G6Pase), α‐smooth muscle actin (SMA), recombinant collagen type III α1 (Col3a1), and connective tissue growth factor (Ctgf) expressions were measured. Stool samples were collected for 16S rDNA sequencing. Results: Compared to the MCD group, AS attenuated liver weight, reduced serum TG, ALT, and AST levels, increased HDL‐C levels, mitigated hepatic steatosis, decreased macrophage infiltration, and augmented ileal ZO‐1 proteins in NASH mice. It also reduced the levels of IL‐6, IL‐1β, and TNF‐α, alongside with the Srebp‐1c mRNA expression. However, no significant effects on Pepck, G6Pase, α‐SMA, Col3a1, or Ctgf were observed. Furthermore, AS promoted diversity and altered gut microbiota composition in NASH mice, causing increased beneficial bacteria like Akkermansia muciniphila, Parabacteroides distasonis, and Prevotellamassilia, which were associated with metabolic functions. Conclusion: FoxO1 inhibitor AS ameliorated hepatic steatosis, inflammation, and intestinal dysbiosis in NASH mice, making it a potentially promising treatment for NASH. [ABSTRACT FROM AUTHOR]

Ultrasonic-assisted ethanol solvent extraction methodology was used to extract anthocyanins from adzuki bean seed skin in this study. On the basis of single factor experiment, the effects of solid-liquid ratio, pH value, ethanol volume fraction, ultrasonic temperature, and ultrasonic power on the extraction effect of anthocyanin were investigated. Furthermore, the extraction process of adzuki bean seed skin was optimized using response surface methodology. The results showed that the priority order of factors affecting the extraction effect of anthocyanins was pH > ultrasonic temperature > ethanol concentration solid-liquid ratio, which also suggested the ultrasonic power had little effect on extraction rate. The optimum conditions for ultrasonic extraction of anthocyanins from adzuki bean seed skin were as follows: solid-liquid ratio 1 34 g/mL, pH value 3, ethanol volume fraction 30%, ultrasonic temperature 55 °C, and the ultrasonic power 350 W. Under the optimum conditions above, the extraction effect of anthocyanins from red bean seed skin reached the optimal value. The content of anthocyanins in the extraction solution reached (82.35 ± 3.28) mg/100 g. [ABSTRACT FROM AUTHOR]

Background: Preventive intervention can significantly reduce the human and economic costs of postpartum depression (PPD) compared with treatment post-diagnosis. However, identifying women with a high PPD risk and making a judgement as to the benefits of preventive intervention is a major challenge.Methods: This is a retrospective study of parturients that underwent a cesarean delivery. Control group was used as development cohort and validation cohort to construct the risk prediction model of PPD and determine a risk threshold. Ketamine group and development cohort were used to verify the risk classification of parturients by evaluating whether the incidence of PPD decreased significantly after ketamine treatment in high-risk for PPD population.Results: The AUC for the development cohort and validation cohort of the PPD prediction model were 0.751 (95%CI:0.700-0.802) and 0.748 (95%CI:0.680-0.816), respectively. A threshold of 19% PPD risk probability was determined, with a specificity and sensitivity in the validation cohort are 0.766 and 0.604, respectively. After matching the high-risk group and the low-risk group by propensity score, the results demonstrated that PPD incidence significantly reduced in the high-risk group following ketamine, versus non-ketamine, intervention (p < 0.01). In contrast, intervention in the low-risk group showed no significant difference in PPD outcomes (p > 0.01).Limitation: Randomized trials are needed to further verify the feasibility of the model and the thresholds proposed.Conclusion: This prediction model developed in this study shows utility in predicting PPD risk. Ketamine intervention significantly lowers PPD incidence in parturients with a risk classification threshold greater than 19%. [ABSTRACT FROM AUTHOR]

Postpartum depressive symptom (PDS) is a common psychological and mental disorder after giving birth. Our previous studies showing the application of dexmedetomidine, an α2-AR agonist, can significantly improve maternal sleep, as well as relieve and reduce the incidence of PDS. This study investigated the association between α2 A AR gene polymorphisms and PDS. A total of 568 cesarean section patients were enrolled; the incidence of PDS is 18.13% (103 with PDS, 465 with non-PDS). The Edinburgh Postpartum Depression Scale score ≥10 was used to diagnose PDS at 42 days after delivery. The single-nucleotide polymorphisms of α2AR were sequenced by pyrosequencing. The effect of rs13306146 A > G polymorphism on α2AR transcription and the regulation of miR-646 on α2AR expression were assessed by dual luciferase reporter assays or gene transfection. Increased stress during pregnancy, poor relationship between mother-in-law and daughter-in-law, spousal relationship, domestic violence, antenatal depression, self-harm ideation, and stressful life events were all associated with increased PDS incidence (p < 0.05). The logistic regression analysis found that the α2AAR rs13306146 polymorphism was associated with PDS after adjusting confounding variables. The transcriptional function of the α2AAR rs13306146 A allele was decreased compared with the G allele, and the α2AAR expression level was correspondingly decreased (p < 0.05), as the strongest binding ability of miR-646 to the α2AAR rs13306146 AA genotype. The effect of α2AAR rs13306146 A > G polymorphism may change the binding ability of miR-646 at the 3′UTR of the α2AAR gene, affecting the expression of α2AAR. This study supports the involvement of the norepinephrine system in the pathogenesis of PDS. Genotypes of α2AAR may be novel and useful biomarkers for PDS. [ABSTRACT FROM AUTHOR]

Aims/Introduction: The predictive value of admission hyperglycemia in the long‐term prognosis of acute myocardial infarction patients is still controversial. We aimed to investigate this value based on the diabetes status. Materials and Methods: We carried out a multicenter, retrospective study of 1,288 acute myocardial infarction patients enrolled in 11 hospitals between March 2014 and June 2019 in Chengdu, China. The patients were classified into those with diabetes and those without diabetes, each was further divided into: hyperglycemia and non‐hyperglycemia subgroups, according to the optimal cut‐off value of the blood glucose to predict all‐cause mortality during follow up. The end‐points were all‐cause death and major adverse cardiovascular and cerebrovascular events, including all‐cause death, non‐fatal myocardial infarction, vessel revascularization and non‐fatal stroke. Results: In the follow‐up period of 15 months, we observed 210 (16.3%), 6 (0.5%), 57 (4.4%) and 34 (2.6%) cases of death, non‐fatal myocardial infarction, revascularization and non‐fatal stroke, respectively. The optimal cut‐off values of admission blood glucose for patients with diabetes and patients without diabetes to predict all‐cause mortality during follow up were 14.80 and 6.77 mmol/L, respectively. We divided patients with diabetes (n = 331) into hyperglycemia (n = 92) and non‐hyperglycemia (n = 239), and patients without diabetes (n = 897) into hyperglycemia (n = 425) and non‐hyperglycemia (n = 472). The cumulative rates of all‐cause death and major adverse cardiovascular and cerebrovascular events among the patients in each hyperglycemia group was higher than that in the corresponding non‐hyperglycemia group (P < 0.001). In patients without diabetes, admission hyperglycemia was an independent predictor of all‐cause mortality and major adverse cardiovascular and cerebrovascular events. Conclusion: Admission hyperglycemia was an independent predictor for long‐term prognosis in acute myocardial infarction patients without diabetes. [ABSTRACT FROM AUTHOR]