Age- and sex-dependent DNA hypomethylation controlled by growth hormone in mouse liver

In mammals, differences in liver function and aging have been observed between sexes; however, the epigenetic mechanisms underlying such differences remain largely unexplored. In this study, we investigated sex- and age-dependent DNA methylation status in the mouse liver. We analyzed 90 known sex-differentially expressed genes, and identified sex-dependent methylation in Zfp809, Hsd3b5, Treh, Cxcl11, Cyp17a1, and Nnmt genes. After 4 weeks of age, we noted the gradual establishment of sex-dependent hypomethylation in each of these genes in either males or females. The exposure of male mice to female-like growth hormone (GH) profile repressed male-predominant hypomethylation and promoted female-predominant hypomethylation. The occurrence of age-dependent hypomethylation, including at loci for which we also observed sex-dependent changes in DNA methylation, was accompanied by the downregulation of DNMT3A/B. In addition, we found that age-dependent hypomethylation was promoted through liver regeneration induced by partial hepatectomy, suggesting that DNMT activities were not enough to retain methylation levels. In conclusion, our results demonstrate that sex-dependent GH profiles influence the age-progressive hypomethylation under decreased DNMT3A/B levels in certain regions of the genome.     

Polyvinyl alcohol scaffolds and supplementation support 3D and sphere culturing of human cancer cell lines by reducing apoptosis and promoting cellular proliferation

Three-dimensional (3D) culturing mimics the heterogeneous cellular conditions of the in vivo tumor microenvironment compared to 2D monolayer-cultured cells and 3D cultures of established cancer cell lines (sphere culture) or patient-derived cancer cells (organoid culture) are frequently used for cancer research or drug screening and evaluation. To establish more cost and time-efficient 3D culture methods for cancer cell lines, we supplemented sphere culture medium with polyvinyl alcohol (PVA) and found that 3D sphere cultures of breast and pancreatic cancer cell lines were significantly increased. Mechanistically, we found that PVA prevented cell death and promoted cellular proliferation while maintaining levels of stemness-related gene expression. Furthermore, we showed that polyvinyl formal resin (PVF) 3D scaffolds made by cross-linked PVA can function in serum-free, long-term 3D cultures to support maintenance of sphere- or tumor-like cell masses for diverse cancer cell types. Taken together, we demonstrate the effectiveness of PVA and PVF in human cancer cell line culture protocols.     

Low-dose levodopa therapy in Japanese patients with Parkinson's disease: a retrospective study

OBJECTIVE: To investigate the efficacy and the rate of adverse events of chronic low-dose levodopa-carbidopa therapy in Japanese patients with Parkinson's disease (PD). PATIENTS AND METHODS: A total of 92 Japanese PD patients treated with low doses of levodopa from the outset were studied. Both disease-specific motor disabilities and quality of life (QOL) in the patients were evaluated using the Unified Parkinson's Disease Rating Scale (UPDRS) and the Parkinson's Disease 39 Quality of Life Questionnaire (PDQ39), respectively. RESULTS: In the overall patient group, the mean duration of treatment, the mean daily dose of levodopa, the disability scores and the motor scores of UPDRS were 6.2 years, 186.4 mg, 8.0 and 19.2, respectively. The rates of motor fluctuations, dyskinesias and hallucinations were 8.7%, 6.5% and 14.1%, respectively. The mean summary index of PDQ39 scores was 23.1. Patients with motor fluctuations showed a significantly earlier disease onset. Dose of levodopa, age at onset, and treatment duration were not associated with the occurrence of dyskinesias. Patients with hallucination had higher doses of levodopa and dopamine agonist. CONCLUSIONS: Our results demonstrate that chronic administration of a low-dose levodopa preparation can provide satisfactory benefit with a low incidence of motor complications, and can result in good QOL in Japanese patients with PD. The concomitant use of a small amount of dopamine agonist and amantadine from the outset has partly contributed to a reduced dose of levodopa and the lesser occurrence of motor complications.     

Effects of aerobic and resistance exercise training on insulin action in the elderly

Background:   Aging is associated with a declining glucose tolerance, which is primarily caused by peripheral insulin resistance, and with a decline in physical activity. The aim of this study was to assess the effect of aerobic and resistance exercise training on insulin action in the elderly.
Methods:   Fourteen healthy male subjects (age: 65–73 years) were enrolled and divided into two exercise groups: resistance training (RT) or a combined aerobic and resistance training (CT). Subjects participated in each training program three times a week for 12 weeks. Before and after the training program, insulin action was determined using the euglycemic clamp technique at insulin infusion rates of 40 (low) or 400 (high) mU/m² per min. Body composition was measured by dual-energy X-ray absorptiometry (DXA).
Results:   Percent fat decreased significantly in both groups. Fat-free mass (FFM) tended to increase in the RT group ( P  = 0.054), but not in the CT group. In the CT group, the glucose infusion rate (GIR) increased 16.6% ( P  < 0.05) at the low insulin infusion rate and 21.7% ( P  < 0.01) at the high rate. In the RT group, GIR tended to increase at the low insulin infusion rate, but was not statistically significant ( P  = 0.052) and increased 9.9% ( P  < 0.05) at the high rate. When calculated per FFM, the increased insulin action persisted in the CT group ( P  < 0.01), but not in the RT group.
Conclusion:   The combination of aerobic and resistance training is more effective for improving the decreased insulin action in the elderly than resistance training alone.     

晨尿微量白蛋白浓度检测对筛检早期糖尿病肾病的临床价值

目的探讨晨尿微量白蛋白浓度检测对筛选早期糖尿病肾病的临床价值.方法110例2型糖尿病病人纳入研究,收集晨尿及24 h尿样,检测晨尿微量白蛋白浓度和24 h尿白蛋白排泄率(UAER),并绘制晨尿白蛋白浓度受试者工作曲线(ROC).结果晨尿微量白蛋白浓度与UAER相关(r=0.93,P＜0.001).晨尿微量白蛋白浓度的ROC 100%敏感度截断点微量白蛋白浓度值为10 mg/L(特异度为69%),敏感度与特异度最佳截断点微量白蛋白浓度值为25mg/L(敏感度90%,特异度88%).结论晨尿微量白蛋白浓度检测对于筛选早期糖尿病肾病准确性较高.且较UAER简便、经济,可作为筛检2型糖尿病早期肾病的方法之一.