Anti-diabetic effect of loganin by inhibiting FOXO1 nuclear translocation via PI3K/Akt signaling pathway in INS-1 cell

Objective(s): JiangTangXiaoKe (JTXK) granule, a Chinese traditional herbal formula, has been clinically used and demonstrated to be beneficial in controlling high glucose and to relieve the symptoms of  Type 2 diabetes mellitus patients for decades. In this study, we explored how loganin, one of the components in JTXK granule, mediated the anti-diabetic effect.Materials and Methods: We generate a cell model with the dysfunction of insulin secretion by over-expression FOXO1 in INS-1 cells. MTT method was used to detect cytotoxicity after treated with Loganin. ELISA analysis was used to examine insulin secretion. The expression levels of FOXO1 and Akt were evaluated by Western blot.Results: Treatment with Loganin did not change the expression level of FOXO1 in INS-1 cells, but increased phosphorylation of FOXO1 and inhibited the nuclear translocation and accumulation of FOXO1, which improved the insulin secretion of the cells. Mechanistically, we found PI3K/Akt signaling pathway involved in these effects, which were blocked by an Akt inhibitor, LY294002.Conclusion: Loganin mediated the subcellular distribution of FOXO1 via PI3K/Akt signaling pathway, which protected the function of insulin secretion in islet INS-1 cells

Salvianolic acid B plays an anti-obesity role in high fat diet-induced obese mice by regulating the expression of mRNA, circRNA, and lncRNA

Background Adipose tissue plays a central role in obesity-related metabolic diseases such as type 2 diabetes. Salvianolic acid B (Sal B), a water-soluble ingredient derived from Salvia miltiorrhiza, has been shown to reduce obesity and obesity-related metabolic diseases by suppressing adipogenesis. However, the role of Sal B in white adipose tissue (WAT) is not yet clear. Methods Illumina Hiseq 4000 was used to study the effects of Sal B on the expression of long non-coding RNA (lncRNA) and circular RNA (circRNA) in epididymal white adipose tissue induced by a high fat diet in obese mice. Results RNA-Seq data showed that 234 lncRNAs, 19 circRNAs, and 132 mRNAs were differentially expressed in WAT under Sal B treatment. The up-regulated protein-coding genes in WAT of the Sal B-treated group were involved in the insulin resistance pathway, while the down-regulated genes mainly participated in the IL-17 signaling pathway. Other pathways may play an important role in the formation and differentiation of adipose tissue, such as B cell receptor signaling. Analysis of the lncRNA–mRNA network provides potential targets for lncRNAs in energy metabolism. We speculate that Sal B may serve as a potential therapeutic approach for obesity

Aqueous Extract of Mori Folium Exerts Bone Protective Effect Through Regulation of Calcium and Redox Homeostasis via PTH/VDR/CaBP and AGEs/RAGE/Nox4/NF-κB Signaling in Diabetic Rats

Purpose: The present study is aimed to explore whether the aqueous extract of Mori Folium (MF) exhibits bone protective effect by regulating calcium and redox homeostasis in diabetic rats, and to identify the signaling pathways involved in this process.Methods: Diabetic rats were established using high-sugar and high-fat diet and streptozotocin (STZ) (30 mg/kg for 3 consecutive days). The serum levels of osteocalcin (OC), insulin-like growth factor-1 (IGF-1), tartrate-resistant acid phosphatase (TRAP), phosphorus (P), calcium (Ca), 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], parathormone (PTH), advanced glycation end products (AGEs), superoxide dismutase (SOD), and malondialdehyde (MDA), total antioxidant capacity (TAC), 8-hydroxy-2′-deoxyguanosine (8-OH-dG), and interleukin 6 (IL-6) were determined by ELISA or biochemical assays. Histopathological alterations in the femurs were evaluated by the stainings of hematoxylin-eosin (H&E) and alizarin red S. In addition, femoral strength was detected by a three-point bending assay, bone microstructure was detected with micro-computer tomography. Bone material properties were examined by Fourier-transform infrared spectroscopy. Furthermore, the expressions of IGF-1, runt-related transcription factor 2 (Runx2), osteoprotegerin (OPG), receptor activator of nuclear factor kappa-B ligand (RANKL), cathepsin K, AGEs, receptor of advanced glycation end products (RAGE), NADPH oxidase 4 (Nox4), and nuclear factor kappa-B (NF-κB) in the femurs and tibias, and the alterations in the levels of calcium-binding protein-28k (CaBP-28k), transient receptor potential V6 (TRPV6), and vitamin D receptor (VDR) in the kidneys and duodenums were determined by western blot and immunohistochemical analysis.Results: Treatment of diabetic rats with MF aqueous extract induces an increase in the levels of OC and IGF-1 as well as a decrease in TRAP level in serum. MF treatment also upregulates the expression of OPG, downregulates the expressions of AGEs, RAGE, Nox4, NF-κB, and RANKL, which leads to improve bone microstructure and strength exhibited by an increase in cortical area ratio, cortical thickness, and trabecular area ratio as well as ultimate load, elastic modulus, and bending stress in the femurs and tibias of diabetic rats. In addition, MF aqueous extract preserves bone material properties by decreasing the ratio of fatty acid/collagen and increasing the ratio of mineral/matrix in the femurs of diabetic rats. Moreover, MF treatment increases the levels of P, Ca, and 1,25(OH)2D3, and decreases the level of PTH in the serum, as well as upregulates the expressions of TRPV6 and VDR in the duodenums and CaBP-28k in the kidneys of diabetic rats. Additionally, MF has ability of rebuilding redox homeostasis and eliminating inflammatory stress by increasing the levels of SOD and TAC as well as decreasing the levels of IL-6, AGEs, MDA, and 8-OH-dG.Conclusions: MF treatment may improve bone quality through maintenance of calcium homeostasis via regulating the PTH/VDR/CaBP signaling, and elimination of oxidative stress via regulating the AGEs/RAGE/Nox4/NF-κB signaling. These results may suggest the potential of MF in preventing the development of diabetic osteoporosis

Reexamining Spatiotemporal Disparities of Financial Development in China Based on Functional Data Analysis

Essentially, financial development is a continuous and time-varying process. This paper explicitly accounts for this by introducing functional data analysis to convert discrete observations into a smooth curve in order to represent the continuous process of financial development at the regional level. Regional disparities in financial development in China are reexamined from three dimensions: financial scale enlargement, financial structure adjustment, and financial intermediary efficiency. Disparities are then decomposed using an extended functional Theil index. It is necessary to introduce functional data into the research of financial development level. Through the functional research of China’s financial development level index of three different dimensions, the financial development level can be studied at the level of speed and acceleration, which fills up the research gap. The results imply that (1) the disparity in the level of financial scale enlargement and disparity in velocity and acceleration of financial intermediary efficiency are both statistically significant across regions, while the regional disparity in financial structure adjustment is insignificant, and (2) the downward trends of the total disparity in three dimensions are all dominated by the declining intraregional disparities. Since all 31 provinces have broken the traditional regional division, China does not need to implement region-specific protective policies in strengthening its deepening financial reforms

an integrated prefetching and caching scheme for mobile web caching system

Int Assoc Comp & Informat Sci, Cent Michigan Univ, Qingdao Technol UnivWeb caching and prefetching play an important role in improving the performance of Web access in wireless environment. In this paper, we present a compact set of algorithms for integrating web caching and prefetching for wireless local area n

Prevalence and Predisposing Factors for Depressive Status in Chinese Patients with Obstructive Sleep Apnoea: A Large-Sample Survey.

Recently, there are few studies reporting on depressive status and obstructive sleep apnoea (OSA) in China. A large-sample survey was to be performed to explore the prevalence of depressive status and related factors in Chinese patients with OSA.From among a randomly-selected group of OSA patients, 1,327 met inclusion criteria. After screening with the Symptom Checklist 90 (SCL-90) and Self-Rating Depression Scale (SDS), patients were assigned to OSA without depressive status (control group, n = 698) and OSA with depressive status (n = 629) groups. Using chi-squared testing, the correlation analyses between the depressive status and OSA patient demographic and clinical variables were tested. Then depression-related risk factors in OSA patients were analysed using stepwise linear regression analysis. The effects of family and social factors on depressive status in OSA patients were investigated using Mann-Whitney U (one of nonparametric test).The prevalence of depressive status was 47.4% in OSA patients. Depressive status was significantly associated with female gender, single status, Family Burden Scale of Disease (FBS), Family APGAR Index (APGAR), apnoea-hypopnea index (AHI), and Perceived Social Support Scale (PSSS). Stepwise linear regression analysis further indicated that single status, hypoxemia, APGAR, AHI, PSSS, AHI, and FBS were all risk factors for depressive status in OSA patients. The total of the FBS score and three of its sub-factors scores (family daily activities, family relationships and mental health of family members) were higher, and the total of the APGAR score and two of its sub-factors scores (adaptability and affection) were lower in OSA with depressive status compared with the control group. Besides, the total score for the PSSS and scores for its two sub-factors (family support and social support) were all lower in OSA patients with depressive status than those of the control group.Depressive status has high comorbid rate in Chinese OSA patients and is significantly associated with single status, apnoea-hypopnea index, hypoxemia, family and social supports

Salvianolic acid B improves glucolipid metabolism by regulating adipogenic transcription factors in mice with diet-induced obesity

Objective: To determine the effect of Salvianolic acid B (Sal B) on glucose and lipid metabolism in mice with high-fat diet (HFD)-induced obesity, and to investigate the underlying mechanisms by measuring the expression levels of key adipogenic transcription factors. Methods: Six-week-old C57BL/6J male mice were fed for 12 weeks with a HFD to induce obesity or a standard diet to serve as normal controls. A mean body weight increase of more than 20% after these 12 weeks was used as the criteria for obesity. HFD-fed obese mice then received a supplement of Sal B (100 mg/kg body weight/day), metformin (75 mg/kg body weight/day) or water (an equivalent volume; served as model controls) by oral gavage for an additional 8 weeks, and the normal controls received water (an equivalent volume) by oral gavage for the same period. Results: Sal B significantly reduced body weight gain (P < .05) without influencing food intake in HFD-fed obese mice relative to model controls. Sal B also reduced the body fat mass of the obese mice relative to model controls in a time-dependent manner (P < .05). Sal B significantly decreased the serum concentrations of low-density lipoprotein cholesterol, total cholesterol, triglyceride and free fatty acids by 25.5%, 20.2%, 20.6% and 13.4%, respectively, and increased the concentration of high-density lipoprotein cholesterol by 50.1% relative to model controls. In addition, Sal B significantly lowered fasting glucose concentrations and improved insulin sensitivity relative to model controls (P < .05). Sal B acted by ameliorating the histopathological changes in both brown and white adipose tissues of obese mice. Moreover, in brown adipose tissue, Sal B up-regulated the mRNA and protein expression of PPARγ and c/EBPα, and the protein expression of PPARα and SREBP-1 (P < .05). In white adipose tissue, Sal B down-regulated the mRNA expression of PPARγ and c/EBPα, and decreased the protein expression of PPARγ and SREBP-1(P < .05). Conclusions: The results suggest that Sal B can reduce body weight gain and regulate glucose and lipid metabolism in mice with diet-induced obesity by regulating adipogenic transcription factors in their adipose tissues