Aspartame (ASP) as an important sugar substitute is widely used in pharmaceutical and food processing. Here, we compared the effects of ASP and sucrose on mice pancreatic islet cells in vivo and observed that ASP with the condition of high concentration and long-term exposure (HASP) could cause insulin secretion (500 mg/kg for 1 month). Next, we conducted iTRAQ mass spectrometry to profile the global phosphoproteome and found that phosphorylation of zipper-interacting protein kinase (ZIPK) in murine pancreatic islet tissues were induced at Thr197, Thr242, Thr282, and Ser328 by high-sucrose (HS) treatment, but only induced at Thr197 and Ser328 by HASP treatment. Simultaneously, phosphorylation of STAT3 could be induced at Tyr705 and Ser727 by HS but not by HASP. Furthermore, presence of activated STAT3 accompanied with autophagy was observed in HS treatment. In turn, the inactivation of STAT3 as well as enhanced expression of caspase 3 was observed in HASP treatment. We generated Thr242APro and Thr282Pro on ZIPK using CRISPR-Cas9 in β-TC3 cells and found the weakened interaction with STAT3 as well as the reduced phosphorylation of STAT3 even under HS stimulation. Finally, we observed that ankyrin repeat domain containing 11 (ANKRD11) could interact with ZIPK and play an inhibitory role in the phosphorylation of Thr242APro and Thr282Pro of ZIPK. However, HASP can induce the retention of ANKRD11 in the cytoplasm by phenylpyruvic acid (the metabolite of ASP). Taken together, this study determined that ASP with high concentration and long-term exposure could lead to caspase-dependent apoptosis of pancreatic islet cells through ANKRD11/ZIPK/STAT3 inhibition. Our results give evidence of adverse effects of aspartame on islet cells in some extreme conditions, which might help people to reconsider the biosafety of non-nutritive sweeteners.

BACKGROUND AND OBJECTIVES The aim of this study was to compare the effects of low-carbohydrate diet (LCD) versus low-fat diet (LFD) on weight loss, glycemic control and metabolic risk factors in individuals with impaired glucose regulation (IGR) after 10-week intervention. METHODS AND STUDY DESIGN In this 10-week randomized controlled trial, 90 obese/overweight adults with IGR were randomly assigned to consume either low-carbohydrate diet (20%-25% energy from carbohydrates, 30%-45% energy from fat, 40%-45% en-ergy from protein), or low-fat diet (40%-55% energy from carbohydrates, 20%-30% energy from fat, 20%-30% energy from protein), or heath education (HE) group. The anthropometry and body composition were collected at baseline, week 4, week 8 and week 10. The glycemia and metabolic indicators were assessed at baseline and week 10. RESULTS A total of 69 participants (mean±SE age: 39.2±1.0 years, 72.5% women) completed the intervention and were included in the final analysis. At week 10, all three groups presented similar mean reduction in weight (LCD: 5.80±0.6 kg; LFD: 6.36±0.57 kg; HE: 4.49±0.98 kg), and fasting blood glucose (LCD: 0.73±0.13 mmol/L; LFD: 0.84±0.17 mmol/L; HE: 0.58±0.14 mmol/L). Additionally, there were no differences in the improvements of TG and liver function markers between diets, the low-fat diet exhibited more favorable effects on TC level. CONCLUSIONS Both diets achieved similar weight loss, fasting glucose, and insulin reduction in short-term, suggesting each diet pattern could be an effective strategy for the prediabetes management.

老年人的肌肉衰减与衰老相关的慢性炎症密切相关.n-3多不饱和脂肪酸(polyunsaturated fatty acids,PUFAs)具有抗炎特性,可能有利于减缓老年人的肌肉衰减进程.近年部分临床研究结果显示,大剂量补充n-3 PUFAs能够增加老年人(尤其是女性)肌肉质量、提高肌肉力量或改善肌肉功能,其机制可能与下调炎症因子基因表达、激活mTOR信号通路等有关,但也有部分研究者未发现这种作用.因此,本文系统总结了近年来n-3 PUFAs对老年人肌肉质量、力量和功能影响的随机对照临床试验,探讨n-3 PUFAs应用于老年人肌肉衰减防治的可能性.

目的 探讨麦绿素对高尿酸血症人群的尿酸、血脂,以及肝、肾功能等代谢性指标的影响.方法 采用平行随机对照干预研究设计,选取2020年7月1日至2021年9月14日浙江大学医学院附属第二医院、金华市中心医院、衢州市柯城区人民医院收治的高尿酸血症患者57例,分为研究组(平衡饮食联合麦记片,32例)和对照组(平衡饮食,25例).收集2组患者干预第1、90天的相关数据.结果 2组患者一般资料比较,差异无统计学意义(P>0.05),具有可比性.2组患者干预前尿酸水平比较,差异无统计学意义(P>0.05);研究组患者干预后尿酸水平较对照组明显降低.麦绿素干预的研究组患者发生尿酸偏高的风险是对照组的0.160倍(95％可信区间:0.044～0.587).结论 麦绿素具有一定降低高尿酸血症患者尿酸的作用.

饮食管理是慢性肾脏病(chronic kidney disease,CKD)防治中关键的一环.植物性饮食是指大部分或全部由植物衍生的食物组成的饮食,含有很少或没有动物性食物.近年来植物性饮食用于防治慢性肾病的研究不断增多.大型流行病学研究及临床干预结果提示,植物性饮食不仅可以降低CKD的患病风险,并且有利于延缓CKD患者肾功能的减退.就植物性饮食防治CKD的研究进展进行综述.

根据《中国居民营养与慢性病状况报告(2020年)》数据显示,居民超重、肥胖问题不断凸显.18岁及以上居民男性和女性的平均体重分别为69.6 千克和59 千克,与2015 年发布结果相比分别增加3.4千克和1.7千克.城乡各年龄组居民超重率、肥胖率继续上升,分别为34.3％和16.4％.经历了一个冬天,你的体重有没有增加呢?新的一年的目标是否还是减肥呢?

超重肥胖是慢性代谢性疾病的主要危险因素,与过早死亡风险增加密切相关.低碳水化合物饮食(LCD)经干预研究证实可在短期内(≤6个月)有效控制超重肥胖患者的体重和体脂肪,涉及的机制包括调节能量代谢、抗炎、抗氧化、改变脂质代谢相关基因表达及调节肠道菌群等.但是对于LCD能否持续减轻体重和降低超重肥胖风险,目前的研究结论并不一致.本文总结LCD控制超重肥胖的作用机制、流行病学研究、干预研究及潜在风险研究的进展,为后续研究与临床应用提供参考.

The objective of the present study was to investigate the effects of polo-like kinase 1 (PLK1) and the phosphorylation of human cell division cycle protein 14A (Cdc14A) by PLK1 on beta-cell function and cell cycle regulation. Mouse beta-TC3 cells were incubated with small interfering RNA (siRNA) to knock down the expression of PLK1. Cell cycle analysis was performed using flow cytometry, and cell proliferation and apoptosis was determined. Insulin secretion was evaluated by a radioimmunoassay under both low and high glucose conditions. Mouse beta-TC3 cells were transfected with a wild type or a non-phosphorylatable Cdc14A mutant (Cdc14A(S351A/363A); Cdc14A(AA)) to investigate whether the phosphorylation of Cdc14A is involved in cellular regulation of PLK1 under high glucose conditions. It was found that PLK1 siRNA significantly promoted cellular apoptosis, inhibited cell proliferation, decreased insulin secretion and reduced Cdc14A expression under both low and high glucose conditions. Cdc14A overexpression promoted beta-TC3 cell proliferation and insulin secretion, while Cdc14A(AA) overexpression inhibited cell proliferation and insulin secretion under high glucose conditions. PLK1 siRNA partially reversed the proliferation-promoting effects of Cdc14A and further intensified the inhibition of proliferation by Cdc14A(AA) under high glucose conditions. Similarly, Cdc14A overexpression partially reversed the insulin-inhibiting effects of PLK1 siRNA, while Cdc14A(AA) overexpression showed a synergistic inhibitory effect on insulin secretion with PLK1 siRNA under high glucose conditions. In conclusion, PLK1 promoted cell proliferation and insulin secretion while inhibiting cellular apoptosis in beta-TC3 cell lines under both low and high glucose conditions. In addition, the phospho-regulation of Cdc14A by PLK1 may be involved in beta-TC3 cell cycle regulation and insulin secretion under high glucose conditions.

BACKGROUNDMicroRNA has been reported to play an important role in congenital heart disease (CHD) in children. Recently, microRNA-486-5p (miR-486-5p) has been found increased in patients with cyanotic heart disease compared with those without heart disease. The present study aimed to investigate the effect of miR-486-5p on hypoxia-induced cardiomyocyte injury to reveal the role of miR-486-5p in cyanotic congenital heart disease (CCHD).METHODSReverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to determine the expression of miR-486-5p in hypoxia-induced H9C2 cells. Dual luciferase reporter gene assay was used to confirm IGF-1 was a direct target of miR-486-5p. miR-486-5p inhibitor and IGF-1-siRNA were transfected into H9C2 cells. The cell viability was detected by MTT. Cell apoptosis was detected using flow cytometry. The expression of IGF-1, Bcl-2, caspase-3, caspase-9, and Bax mRNA and protein were detected by RT-qPCR and western blotting, respectively.RESULTSmiR-486-5p expression gradually increased with prolonged hypoxia time in H9C2 cells. Dual luciferase reporter gene results confirmed IGF-1 was a direct target of miR-486-5p. In addition, inhibition of miR-486-5p significantly increased the hypoxia-induced decrease in cell survival and attenuated hypoxia-induced apoptosis. Furthermore, inhibition of miR-486-5p significantly attenuated the hypoxia-induced decrease in the level of IGF-1 and Bcl-2 and the increase in pro-apoptotic proteins such as caspase-3, caspase-9 and Bax. These effects could be reversed by IGF-1-siRNA.CONCLUSIONThe data demonstrated that inhibition of miR-486-5p increased cardiomyocyte growth and reduced cell apoptosis under hypoxic conditions by targeting IGF-1, indicating that miR-486-5p may be an effective target for the treatment of CCHD.

Objective To investigate the association between plasma levels of nucleotide-binding oligomerization domain-like (NOD)-like receptor protein 3 (NLRP3) and high mobility group box-1 (HMGB1) and their prognostic significance in neonatal patients with congenital heart disease (CHD). Methods This study enrolled neonatal patients with CHD and collected their demographic and clinical data. Plasma concentrations of NLRP3 and HMGB1 were measured using enzyme-linked immunosorbent assays. Spearman’s analysis was used to determine the correlation between NLRP3 and HMGB1 levels. The association between NLRP3 and HMGB1 levels and 2-year survival and mortality were evaluated using Kaplan–Meier curve and logistic regression analyses. Results A total of 84 neonatal patients with CHD were included in the study. Plasma NLRP3 and HMGB1 levels were significantly higher in deceased patients compared with those that survived. There was a positive correlation between NLRP3 and HMGB1 levels in neonatal patients with CHD. Patients with elevated levels of NLRP3 and HMGB1 showed significantly lower 2-year survival and higher mortality rates compared with those with lower NLRP3 and HMGB1 levels. Conclusion Neonatal patients with CHD and a poor prognosis had higher NLRP3 and HMGB1 levels, which suggests that these might be potential biomarkers of CHD prognosis.