Exosomes Derived from Human Umbilical Cord Mesenchymal Stem Cells Enhance Insulin Sensitivity in Insulin Resistant Human Adipocytes.

Insulin resistance is an essential characteristic of type 2 diabetes mellitus (T2DM), which can be induced by glucotoxicity and adipose chronic inflammation. Mesenchymal stem cells (MSCs) and their exosomes were reported to ameliorate T2DM and its complications by their immunoregulatory and healing abilities. Exosomes derived from MSCs contain abundant molecules to mediate crosstalk between cells and mimic biological function of MSCs. But the role of exosomes derived from human umbilical cord mesenchymal stem cells (hUC-MSCs) in insulin resistance of human adipocytes is unclear. In this study, exosomes were harvested from the conditioned medium of hUC-MSCs and added to insulin-resistant adipocytes. Insulin-stimulated glucose uptake was measured by glucose oxidase/peroxidase assay. The signal pathway involved in exosome-treated adipocytes was detected by RT-PCR and Western blotting. The biological characteristics and function were compared between hUC-MSCs and human adipose-derived mesenchymal stem cells (hAMSCs). The results showed that hAMSCs had better adipogenic ability than hUC-MSCs. After induction of mature adipocytes by adipogenesis of hAMSC, the model of insulin-resistant adipocytes was successfully established by TNF-α and high glucose intervention. After exosome treatment, the insulin-stimulated glucose uptake was significantly increased. In addition, the effect of exosomes could be stabilized for at least 48 h. Furthermore, the level of leptin was significantly decreased, and the mRNA expression of sirtuin-1 and insulin receptor substrate-1 was significantly upregulated after exosome treatment. In conclusion, exosomes significantly improve insulin sensitivity in insulin-resistant human adipocytes, and the mechanism involves the regulation of adipokines.

Investigation of a plasmid containing a novel immunotoxin VEGF165-PE38 gene for antiangiogenic therapy in a malignant glioma model.

Inhibition of tumor neovascularization has profound effects on the growth of solid tumors. Our previous studies have shown the effect of VEGF165-PE38 recombinant immunotoxin on proliferation and apoptosis in human umbilical vein endothelial cells in vitro. In this study, we explored the direct inhibition of angiogenesis in chick chorioallantoic membrane and antiangiogenic therapy in a malignant glioma model. HEK293 cells were transfected with the pVEGF165PE38-IRES2-EGFP plasmid. ELISA was used to confirm the expression of VEGF165-PE38 in the transfected cells. These cells released 1396 + or - 131.9 pg VEGF165-PE38/1x10(4) cells/48 h into the culture medium and the supernatant was capable of inhibiting the growth of capillary-like structures in chick chorioallantoic membrane assay. In a murine malignant glioma model, plasmid was directly administered via multiple local intratumoral delivery. After day 16 the tumor volume in mice treated with pVEGF165PE38-IRES2-EGFP was significantly lower than that in mice in the control groups. Immunohistochemistry studies showed that the treated group had decreased expression of CD31. Quantitative analysis of microvessel density in the treated group was 1.99 + or - 0.69/0.74 mm(2), and was significantly lower than that in the control groups (9.33 + or - 1.99/0.74 mm(2), 8.09 + or - 1.39/0.74 mm(2) and 8.49 + or - 1.69/0.74 mm(2)). Immunohistochemistry analysis indicated that immunotoxin VEGF165-PE38 was distributed in the treated group in malignant glioma tissue. Our findings provide evidence that the in vivo production of VEGF165-PE38 through gene therapy using a eukaryotic expression plasmid had potential antiangiogenic activity in malignant glioma in vivo.

Maternal exercise and its beneficial effects on glucose metabolism in offspring.

It shows that detrimental exposures and conditions in mothers can lead to the development of obesity and type 2 diabetes in offspring. This can lead to a vicious cycle of metabolic dysfunction, where rising rates of obesity, pre-diabetes, and diabetes in individuals of reproductive age, propagating risks to subsequent generations. It is well established that regular exercise has important health benefits for people with obesity and type 2 diabetes. Recently, increasing studies aim to examine the effects of maternal exercise on metabolic health in offspring. This review aims to demonstrate the evidence linking maternal exercise during critical periods of development and its implications for glucose metabolism in offspring, including intervention timing, sexual dimorphism, different exercise type, and intensity. Then we further examine the potential role of epigenetic modifications in this process.

Potential contribution of the gut microbiota to hypoglycemia after gastric bypass surgery.

Obesity has become a global health problem. Lifestyle modification and medical treatment only appear to yield short-term weight loss. Roux-en-Y gastric bypass (RYGB) is the most popular bariatric procedure, and it sustains weight reduction and results in the remission of obesity-associated comorbidities for obese individuals. However, patients who undergo this surgery may develop hypoglycemia. To date, the diagnosis is challenging and the prevalence of post-RYGB hypoglycemia (PRH) is unclear. RYGB alters the anatomy of the upper gastrointestinal tract and has a combined effect of caloric intake restriction and nutrient malabsorption. Nevertheless, the physiologic changes after RYGB are complex. Although hyperinsulinemia, incretin effects, dysfunction of ß-cells and α-cells, and some other factors have been widely investigated and are reported to be possible mediators of PRH, the pathogenesis is still not completely understood. In light of the important role of the gut microbiome in metabolism, we hypothesized that the gut microbiome might also be a critical link between RYGB and hypoglycemia. In this review, we mainly highlight the current possible factors predisposing individuals to PRH, particularly related to the gut microbiota, which may yield significant insights into the intestinal regulation of glucose metabolic homeostasis and provide novel clues to improve the treatment of type 2 diabetes mellitus.

Early-life nutrition and metabolic disorders in later life: a new perspective on energy metabolism.

Type 2 diabetes mellitus and metabolic disorders have become an epidemic globally. However, the pathogenesis remains largely unclear and the prevention and treatment are still limited. In addition to environmental factors during adulthood, early life is the critical developmental window with high tissue plasticity, which might be modified by external environmental cues. Substantial evidence has demonstrated the vital role of early-life nutrition in programming the metabolic disorders in later life. In this review, we aim to overview the concepts of fetal programming and investigate the effects of early-life nutrition on energy metabolism in later life and the potential epigenetic mechanism. The related studies published on PubMed database up to March 2020 were included. The results showed that both maternal overnutrition and undernutrition increased the riskes of metabolic disorders in offspring and epigenetic modifications, including DNA methylation, miRNAs, and histone modification, might be the vital mediators. The beneficial effects of early-life lifestyle modifications as well as dietary and nutritional interventions on these deleterious metabolic remolding were initially observed. Overall, characterizing the early-life malnutrition that reshapes metabolic disease trajectories may yield novel targets for early prevention and intervention and provide a new point of view to the energy metabolism.

Structural elucidation of three antioxidative polysaccharides from Tricholoma lobayense.

Tricholoma lobayense is a nutritious mushroom with great health benefits. Three polysaccharides with purity higher than 99% were successfully extracted from Tricholoma lobayense. The molecular weights of TLH-1, TLH-2 and TLH-3 were determined to be 8.43×105，5.36×105 and 4.53×103Da, respectively. The backbones of TLH-1 and TLH-2 were mainly composed of 1,4-linked α-d-glucopyranosyl. However, polysaccharide TLH-3 was found to be a highly branched glucogalactan, which is made up of 1,3-linked α-d-glucopyranosyl branched at C-6 and 1,3-linked ß-d-galactopyranosyl. In vitro antioxidant activity assays revealed that TLH-3 exhibited highest antioxidant activities among the polysaccharides from Tricholoma lobayense, which were comparable to those of ascorbic acid. The results suggested that the outstanding antioxidant activities of TLH-3 might depend on its low molecular weight, high branch degree, versatile linkage types and complex conformation. These characteristics make TLH-3 an attractive natural antioxidant for food and pharmaceutical applications.

[Clinical analysis of 4 treatments for woman polycystic ovarian syndrome with infertility].

OBJECTIVE: To investigate the therapeutic effects of 4 different treatments for woman polycystic ovarian syndrome (PCOS) with infertility. METHODS: One hundred and twenty women PCOS with infertility were divided into 4 Groups : patients in Group 1 were directly treated with clomiphene (CC)/CC + human menopausal gonadotropin (HMG) + human chorionic gonadotropin (HCG) to accelerate ovulation; patients in Group 2 were treated with the same way as Group 1 after taking marvolon for 2 cycles; patients in Group 3 took marvolon for 2 cycles and metformin for 8 weeks, and then were treated the same as Group 1; patients in Group 4 were treated with laparosocopy. The body mess index (BMI), emmenia period, weight, volume of ovary, LH, and T were measured before and after the treatment in all patients. The cycle ovulatory rate and occurrence rate of luteinized unruptued follicle syndrome (LUFS) within 2 months and the pregnancy rate within 6 months after the treatment were also observed. RESULTS: In all patients, BMI, emmenia period, serum T, and serum LH decreased significantly (P <0.05 or 0.01). The body mess indexes were significantly lower in Group 2 and Group 3 than those in Group 4 and Group 1, and Group 4 was also lower than Group 1 (P < 0.05 or 0.01). There was no difference in emmenia period between the 4 groups (P = 0.289). The volumes of ovary were enlarged in Group 1, and they were shrunk in the residual groups, which was significantly lower in Group 4 than in Group 2 and 3 (P < 0.01). The cycle ovulation rates were 53%, 72 %, 78 %, and 76%; the pregnancy rates within 6 months were 20%, 47%, 50%, and 57%, respectively; and they were significantly higher in the Group 2, 3 and 4 than in Group 1 (P <0.01). The occurrence rates of LUFS were 32%, 16%, 15%, and 13%, and they were significantly lower in Group 2, 3 and 4 than in Group 1 (P <0. 01). CONCLUSION: The effects of marvolon or marvolon and metformin are the same as those of laparoscopy not only in controlling the symptoms of PCOS, but also in increasing the cycle ovulation rate, pregnancy rate within 6 months, and decreasing the occurrence rate of LUFS. The symptoms of PCOS can be controlled better, but the cycle ovulation rate and pregnancy rate within 6 months can not be improved when clomiphene is used alone.

The Ras/Raf/MEK/ERK signaling pathway and its role in the occurrence and development of HCC.

Hepatocellular carcinoma (HCC) is the fifth most common tumor worldwide and has a very poor prognosis. Its occurrence has been on the increase in recent years. Surgical resection and liver transplantation are the primary methods of treatment for HCC patients, but can only be applied to 15% of patients. The median survival time of unresectable or metastasizing HCC patients is only a few months. Existing systemic treatment methods are not effective for advanced HCC patients and a new method of treatment is needed for these patients. It has been established that the HCC occurs in multiple stages, however, the pathogenesis at a molecular level is not clear and many key factors are yet to be determined. In the past 30 years, it has become evident that the Ras/Raf/MEK/extracellular signal-regulated kinase (ERK) signaling pathway plays a significant role in the occurrence and development of HCC. This review focused on the association between the Ras/Raf/MEK/ERK signaling pathway and HCC.

[Pollution Assessment and Spatial Distribution Characteristics of Heavy Metals in Soils of Coal Mining Area in Longkou City].

The present paper takes the coal mining area of Longkou City as the research area. Thirty-six topsoil (0-20 cm) samples were collected and the contents of 5 kinds of heavy metals were determined, including Cd, As, Ni, Ph, Cr. Geo-statistics analysis was used to analyze the spatial distribution of heavy metals. Principal component analysis (PCA) was used to explore the pollution sources of heavy metals and the degree of heavy metals pollution was evaluated by weighted average comprehensive pollution evaluation method. The results showed that enrichment phenomenon was significant for the 5 kinds of heavy metals. Taking secondary standard of National Environment Quality Standard for Soil as the background value, their exceed standard rates were 72.22%, 100%, 100%, 91.67%, 100%, respectively. Average contents of heavy metals in the soil samples were all over the national standard level two and were 1.53, 11.86, 2.40, 1.31, 4.09 times of the background value. In addition, the average contents were much higher than the background value of the topsoil in the eastern part of Shandong Province and were 9.85, 39.98, 8.85, 4.29, 12.71 times of the background value. According to the semivariogram model, we obtained the nugget-effects of 5 kinds of heavy metals and their values were in the order of As (0.644) > Cd (0.627) > Cr (0.538) > Ni (0.411) > Pb (0.294), all belonging to moderate spatial correlation. On the whole, the central part of the Sangyuan Coal Mine and its surrounding areas were the most seriously polluted, while the pollution of heavy metals in the east and west of the study area was relatively light. Principal component analysis suggested that the enrichment of Cd, As, Ni, Cr was due to irrigation of wastewater, the discharge of industry and enterprise, and the industrial activity. Automobile exhaust and coal combustion were the main pollution sources of Pb. The single-factor assessment of heavy metals pollution showed that the degree of different heavy metals pollution was in the order of As > Cr > Ni > Cd > Pb. Simultaneously, comprehensive pollution evaluation showed that the degree of heavy metals pollution in the study area was very serious, with comprehensive pollution index ranging from 2.17 to 4.66, among which, the numbers of moderate and heavy pollution samples were 10 and 26, respectively. Areas with heavy pollution were mainly distributed in the Sangyuan Coal Mine, Beizao Coal Mine, Liuhai Coal Mine; and the areas with moderate pollution covered Wali Coal Mine, Liangjia Coal Mine, and other regions. The results of this paper will provide data reference and theoretical support for the study of ecological risk assessment in the study area.

Blood pressure control rate and associated risk factors in hospitals of different grades in Chongqing, China.

OBJECTIVE: The present article aimed to provide accurate estimate of the control rate of hypertension and the influencing factors in hospitals of different grades in Chongqing. METHODS: In this survey, hypertensive outpatients were recruited from 5 tertiary hospitals, 6 secondary hospitals and 5 primary hospitals in 9 districts of Chongqing from November 2011 to May 2012. Outpatients were investigated by clinical interview with BP measurement and questionnaire. Univariate analyses and logistic regression analysis was used to assess the effect of variables on control of hypertension. RESULT: A total of 2742 hypertensives were studied, of which 820 were from primary hospitals, 901 from secondary hospitals and 1021 from tertiary hospitals. The total control rate for hypertensive outpatients in Chongqing was 46.0%. The control rate of the primary,secondary and tertiary hospitals were 38.7%、46.7%、51.1%. Multinomial Logistic Regression showed that the control rate was positively correlated with mastery of knowledge of hypertension, normal BMI;whereas it was positively correlated with peasantry,the dissatisfactory with doctor's manner and the distrust to doctor. CONCLUSION: Blood pressure control rate of hypertensive outpatients in Chongqing was low.High BMI, peasantry, lack of knowledge of hypertension, doctors' manners, distrust to doctor were the key reasons for low BP control rate.

In vivo magnetic resonance tracking of Feridex-labeled bone marrow-derived neural stem cells after autologous transplantation in rhesus monkey.

Bone marrow stroma cells-derived neural stem cells (BMSCs-D-NSCs) transplantation is a promising strategy for the treatment of nervous system disorders. The development of a non-invasive method to follow the fate of BMSCs-D-NSCs in vivo is very important for the future application of this treatment. In this paper, we show for the first time, that BMSCs-D-NSCs from rhesus monkeys can be labeled in vitro with the superparamagnetic iron oxide (SPIO) contrast agent Feridex and Poly-L-lysine (PLL) without affecting morphology, cell cycle, telomerase activity, proliferation and differentiation ability of the labeled cells. Furthermore, when autografted into the striatum, these cells survived, differentiated and were incorporated into the brain, and could be reliably tracked using MRI, as confirmed by histological examination of the grafting sites with PKH(67) fluorescence. These results suggest that Feridex labeling of BMSCs-D-NSCs is feasible, efficient and safe for MRI tracing following autografting into the rhesus monkey nervous system.