Search

Layer‐by‐layer multilayered film has been creating great opportunities in developing controlled drug and other bioactive molecular delivery system. In this work, coumarin bearing micelles of poly(acrylic acid‐coumarin methacrylate) is first synthesized in a one‐step copolymerization and the reversible photo‐crosslinkable multilayers containing coumarin groups are then fabricated via layering the micelles with polyethyleneimine (PEI). The film growth behavior of polyetheleneimine/poly(acrylic acid‐coumarin methacrylate) (PEI/P(AA‐r‐CMA)) multilayer is found to rely on deposit solution pH. Increasing PEI solution pH and decreasing P(AA‐r‐CMA) pH can greatly accelerate film growing process. This is explained by PEI diffusivity and destabilization of P(AA‐r‐CMA) micelle at solution/multilayer interface. Nile red (NR) is loaded into the film as a model drug via simple post diffusion driven by hydrophobic interactions. Furthermore, photo‐crosslink and decrosslink of PEI/P(AA‐r‐CMA) film is achieved by irradiating the films with light of 365 and 254 nm wavelength, respectively, which therefore ensures the possibility of fine control over drug delivery procedure. [ABSTRACT FROM AUTHOR]

BECN1, a protein essential for autophagy, is involved in adipocyte differentiation, lipolysis and insulin resistance. The discovery of new mechanisms for modifying BECN1 in adipocytes may provide novel therapeutic targets for obesity. This study aimed to investigate the impact of mutations at the acetylation sites of BECN1 on adipocyte differentiation and lipolysis. We found that Ace‐BECN1 levels were increased in 3T3‐L1 adipocyte differentiation and isoproterenol‐/TNF‐α‐stimulated lipolysis and in subcutaneous and visceral adipose tissues of high‐fat diet mice. K414 was identified as an acetylation site of BECN1, which affects the stability of the BECN1 protein. Mutation at K414 of BECN1 affected autophagy, differentiation and lipolysis in 3T3‐L1 adipocytes. These data indicated the potential of BECN1 K414 as a key molecule and a drug target for regulating autophagy and lipid metabolism in adipocytes. [ABSTRACT FROM AUTHOR]

Background: Associations between sex hormones and diabetic vascular complications have recently been studied, but the role luteinizing hormone (LH) plays in diabetic kidney disease (DKD) remains uncertain. We aimed to investigate the relationship of LH and DKD in Chinese men and postmenopausal women with type 2 diabetes mellitus (T2DM). Methods: Data were collected from 1775 T2DM men and postmenopausal women in hospital. The odds ratios (OR) and corresponding 95% confidence intervals (CI) in relation to LH quartiles were obtained by multiple logistic regression analysis. Results: LH levels were significantly higher in patients with macroalbuminuria than in those with microalbuminuria, but were not higher in patients with microalbuminuria than in those with normoalbuminuria. Consistently, LH in those with an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73m2 were significantly higher than in those with eGFR≥60 mL/min/1.73m2. The prevalence of macroalbuminuria was obviously increased for subjects of the fourth quartile of LH vs the first to third quartile (20.4% vs 6.2%, 8.0%, 12.2% in men; 25.3% vs 5.5%, 3.8%, 9.3% in postmenopausal women). Multivariate logistic regression demonstrated that subjects within the highest quartile of LH had higher odds of macroalbuminuria than those within the lowest quartile (OR 4.00, 95% CI, 1.87‐8.55 for men; OR 9.62, 95% CI, 3.42‐27.08 for postmenopausal women), independent of age, diabetes duration, or other metabolic factors. The area under the curve for detecting macroalbuminuria based on LH was 0.662 for men, and 0.767 for postmenopausal women. Conclusion: High LH levels are positively associated with established DKD among Chinese men and postmenopausal women. Elevated LH may be a promising clinical factor for identifying established DKD. [ABSTRACT FROM AUTHOR]

We aimed to determine whether sodium-glucose cotransporter type 2 inhibitors (SGLT2is) and incretin-based agents combination therapy produces more benefits than SGLT2is alone in patients with type 2 diabetes mellitus (T2DM). PubMed, Embase, and the Cochrane Library were searched for randomized controlled trials (RCTs) comparing SGLT2is plus Dipeptidyl-Peptidase 4 inhibitors (SGLT2is/DPP4is) or glucagon like peptide-1 receptor agonists (SGLT2is/GLP-1RAs) against SGLT2is as monotherapy or add-on to metformin in T2DMs. A total of 13 studies with 7350 participants were included. Combination with GLP-1RAs exhibited more HbA1c reduction (WMD: -0.8; 95% CI, -1.14 to -0.45%), weight loss (-1.46; 95% CI, -2.38 to -0.54 kg), and systolic blood pressure (SBP) reduction (-2.88; 95% CI, -4.52 to -1.25 mmHg) versus SGLT2is alone but increased the gastrointestinal disorder risk (RR: 1.68; 95% CI, 1.14-2.47). Combination with DPP4is exhibited an extra effect on HbA1c reduction (-0.47; 95% CI, -0.58 to -0.37%), a neutral effect on weight (0.19; 95% CI, -0.11 to 0.48 kg) and SBP (-0.01; 95% CI, -0.85 to 0.63 mmHg), and ameliorated the genital infections risk (0.73; 95% CI, 0.54-0.97) versus SGLT2is. Meta-regression indicated the hypoglycemic efficacy of SGLT2is/DPP4is is higher in Asians than in other ethnics, and the differences in BMI across ethnic groups may mediate this effect. SGLT2is and incretin-based agents combination therapy is efficacious and safe versus SGLT2is alone in T2DMs. Particularly, combination with GLP-1RAs shows additional benefits to glycemic, weight, and SBP control to a larger extent than DPP4is, while combination with DPP4is ameliorates the risk for genital infection seen with SGLT2is. We highlight the need for individualized treatment related to the selection of this novel combination therapy. [ABSTRACT FROM AUTHOR]