Paeoniflorin Effect of Schwann Cell-Derived Exosomes Ameliorates Dorsal Root Ganglion Neurons Apoptosis through IRE1α Pathway

Background. Diabetic peripheral neuropathy (DPN) is a common complication of diabetes but its pathogenesis is not fully clarified. Endoplasmic reticulum (ER) stress has been confirmed to be involved in the development of DPN. Dorsal root ganglion neuron (DRGn) is the target cell of DPN injure in the peripheral neurons system. Schwann cell (SCs)-derived exosomes (SC-EXOs) can carry IRE1α signal transduction factors in ER stress to DRGn. The aim of this study is to investigate the effect of SC-EXOs treated with paeoniflorin (PF) on DRGn stimulated by high glucose. Methods. SCs were divided into Control group (Control), 150 mM glucose group (HG), high osmotic pressure group (HOP), and low, middle, and high dose PF group (PF1, PF10, and PF100). Exosomes were obtained from SCs by ultracentrifugation and identified according to marker proteins, including CD63, Alix, Hsp70, and TSG101. ER stress initiating factor GRP78, the IRE1α pathway information transmission factor IRE1α, and the phosphorylation level of IRE1α were detected by Western blot, DRGn is divided into Control group (Control), 50 mM glucose group + Control exosomes group (HG + EXOs Control), 50 mM glucose group (HG), and 50 mM glucose group + administration exosomes group (HG + EXOs PF1, HG + EXOs PF10, and HG + EXOs PF100); ER morphology of primary DRGn was observed by using the transmission electron microscope, the level of DRGn apoptosis was analyzed by TUNEL, and the downstream proteins of ER stress including CHOP, XBP1S, JNK, and p-JNK in DRG and the expression of apoptosis-related proteins Bcl-2, Bax, Caspase-3, and Caspase-12 were measured by Western blot. Results. Compared with the exosomes in the HG group, the exosomes after the intervention of PF can significantly reduce the expression of GRP78, IRE1α, and the phosphorylation level of IRE1α P < 0.05 ; compared with the DRGn in the HG group, the SC-EXOs treated with PF could regulate the expression of proteins downstream of IRE1α pathway in ER stress ( P < 0.05 or P < 0.01 ), improve the morphological integrity of ER, and reduce apoptosis in DRGn ( P < 0.05 or P < 0.01 ). Conclusion. PF regulates the information of ER stress carried by SC-EXOs and further affects downstream of IRE1α pathway in DRGn, thus reducing ER stress-induced apoptosis. PF can interfere with DPN through affecting information communication carried by EXOs between SCs and DRGn.

The protective effects of melatonin in high glucose environment by alleviating autophagy and apoptosis on primary cortical neurons

Cognitive dysfunction has been regarded as a complication of diabetes. Melatonin shows a neuroprotective effect on various neurological diseases. However, it’s protective effect on cortical neurons in high glucose environment has not been reported. Our present study aims to observe the protective effect of melatonin on rat cortical neurons and its relationship with autophagy in high glucose environment. The rat primary cortical neurons damaged model was induced by high glucose. The CCK-8, flow cytometry, Western Blot and immunofluorescence methods were used to examine the cell viability, apoptosis rate and proteins expression. Our results showed that there were no differences in cell viability, apoptosis rate, and protein expression among the control MLT and mannitol group. The cell viability of the glucose group was significantly lower than that of the control group, and the apoptosis rate of the glucose group was significantly higher than that of the control group. Compared with the glucose group, the glucose + melatonin group showed a significant increase in cell viability and a notable decrease in apoptosis rate. Melatonin concentration of 0.1-1 mmol/L can significantly reduce the injury of cortical neurons by high glucose. Compared with the control group, the glucose group showed a significant reduction of Bcl-2 protein expression, while remarkable elevations of Bax, caspase-3, Beclin-1 and LC3B levels. The neurons pre-administered with melatonin obtained significantly reversed these changes induced by high glucose. The phosphorylation levels of Akt and mTOR in the glucose group were significantly lower than those in the control group, were significantly increased in the glucose + MLT group compared with the glucose group. These data indicated that melatonin has a neuroprotective effect on cortical neurons under high glucose environment, which may work by activating Akt/mTOR pathway and following the down-regulation of autophagy.

Effect of Liver Kinase B1 on Osteogenic/Adipogenic Differentiation of Bone Marrow Mesenchymal Stem Cells in High Glucose Environment

Bone marrow mesenchymal stem cells (BMSCs) present reduced proliferation under high glucose condition. Liver kinase B1 (LKB1) can maintain the homeostasis of hematopoietic stem cells. However, whether LKB1 regulates BMSCs osteogenic/adipogenic differentiation under high glucose is unclear. Rat BMSCs were isolated and separated into control group, high glucose group, and LKB1 group (BMSCs were transfected with pc-DNA 3.1-LKB1 plasmid under high glucose condition) followed by analysis of LKB1 expression by Real time PCR and Western blot, osteocalcin, type I collagen, RUNX2 and OPN mRNA level by real-time PCR, FABP4 and PPARγ2 level by western blot. In high glucose group, LKB1 expression was significantly decreased, with reduced expression of osteocalcin, type I collagen, RUNX2 and OPN mRNA and elevated FABP4 and PPARγ2 level compared to control group (P < 0.05). Transfection of LKB1 plasmid reduced LKB1 expression, upregulated osteocalcin, type I collagen, RUNX2 and OPN mRNA and downregulated FABP4 and PPARγ2. Compared with the high glucose group, there was a statistical difference (P <0.05). High glucose can inhibit LKB1 expression and BMSCs osteogenic differentiation, and promote adipogenic differentiation. Upregulating LKB1 expression can promote BMSCs osteogenic differentiation.

Association between fasting blood glucose levels at admission and overall survival of patients with pancreatic cancer

Background The associations between fasting blood glucose and staging and overall survival of patients with pancreatic cancer are still controversial. This study aimed to investigate the association between fasting blood glucose levels and overall survival (OS) of patients with pancreatic cancer and to evaluate the impact of differentiation and staging of pancreatic cancer. Methods This was a retrospective study of patients with pathologically confirmed pancreatic cancer admitted to Shengjing Hospital of China Medical University between 01/2012 and 12/2016. The outcome was the OS. The factors associated with OS were examined using univariable and multivariable Cox and logistic regression analyses. Results A total of 253 patients were included. Preoperative blood glucose levels were not significantly associated with the OS of patients with pancreatic cancer (HR = 1.04, 95%CI: 0.78–1.40, P = 0.781). Only CA199 > 1000 was independently associated with OS (HR = 1.86, 95%CI: 1.15–3.02, P = 0.012). The median survival in the normal glucose group was 20.5 months (95% confidence interval (CI): 14.2–26.9). The median survival in the high glucose group was 14.2 months (95% CI: 9.7–18.6). There was no statistically significant difference between the two groups (P = 0.573). Multivariable logistic regression analyses were performed to determine if blood glucose levels influenced the 1- and 2-year OS. No significant association was observed for 1-year (OR = 1.27, 95%CI: 0.71–2.29, P = 0.418) or 2-year (HR = 1.37, 95%CI: 0.76–2.46, P = 0.296) OS. Conclusions Fasting blood glucose levels are not associated with the OS of patients with pancreatic adenocarcinoma.

Impact of In-Ovo Injection of Folic Acid and Glucose on Hatchability and Post-Hatching Performance of Broiler Chicken

The present study was designed to investigate the impact of in-ovo injection of folic acid and glucose on hatching eggs from 55 weeks old broiler breeders. A total number of 900 hatching eggs were collected from Arbor Acres broiler breeders, then, eggs were divided into 6 groups including 1) Negative Control (non-injected, NC), 2) Dry Punch Control (pricked without injecting any solution, DPC), 3) Positive Control (eggs were injected with 0.5 mL normal saline, PC), 4) Folic Acid group (eggs were injected with 0.2 mg/ egg folic acid, FA), 5) Glucose group (eggs were injected with 125 mg/ egg glucose, Glu), and 6) Folic Acid with Glucose group (eggs were injected with 0.2 mg folic acid with 125 mg/ egg glucose, FA+Glu). Each treatment was divided into five replicates of 30 eggs each. Eggs were injected into the albumen under the air sac. After in-ovo injection, the eggs were stored for four days before hatching. After hatching, the chickens were reared in groups according to the treatments. All treatments were divided into 10 replications of 9 chickens in each. In-ovo injection with folic acid decreased the albumen pH significantly to 9.19 after 4 days of injection, while the negative control was 9.43. Hatching quality was severely affected by all in-ovo injection treatments, but no significant differences were found between the treatment groups concerning the hatchability of fertile eggs. Injection treatments had no significant effect on the growth rate or the production number in any of the weeks. Injection of folic acid and (FA+Glu) significantly increased chickens’ body weight at two and four weeks of age. Also, the dressing percentage when using folic acid and (FA+Glu) was significantly increased to 72.1% and 72.5%, respectively, compared to the positive control group (68.3%). In conclusion, our data suggested that in-ovo injection with a mixture of folic acid and glucose (0.2 mg folic acid+ 125 mg/ egg glucose) could be used to enhance carcass characteristics. Further studies should be conducted to find the effects of in-ovo injection folic acid and glucose on different incubation days and at different sites of injection.

Value of peak strain dispersion in discovering left ventricular dysfunction in diabetes mellitus

Cardiovascular disease is one of the main causes of death in diabetes mellitus (DM) patients. The aim of the current study was to explore the value of peak strain dispersion (PSD) for discovering early-stage left ventricular (LV) dysfunction in type 2 diabetes mellitus (T2DM) patients. One hundred and one T2DM patients and sixty healthy subjects were selected for this study. T2DM patients were further divided into controlled blood glucose (HbA1c < 7%, n = 46) and uncontrolled blood glucose (HbA1c ≥ 7%, n = 55) subgroups. All participants underwent conventional echocardiography and two-dimensional speckle-tracking echocardiography. Our results showed that an obvious difference was not observed in global longitudinal strain (GLS) between the controlled blood glucose group and the control group (− 20.34% vs − 21.22%, P = 0.068). Compared with the healthy controls, the uncontrolled blood glucose group showed an impaired GLS (− 18.62% vs − 21.22%, P < 0.001). Nevertheless, PSD was appreciably increased in the controlled blood glucose group (36.02 ms vs 32.48 ms, P = 0.01) and uncontrolled blood glucose group (57.51 ms vs 32.48 ms, P < 0.001). Multivariate linear regression analysis showed that HbA1c was closely related to PSD lesion in the LV in the T2DM group (β = 0.520, P < 0.001). PSD plays an important role in evaluating the coordination and synchronization of myocardial movement and provides a more accurate and sensitive index assessment of early LV systolic function in T2DM patients. In addition, HbA1c levels were related to LV dysfunction.

Effects of icariin and quercetin on high glucose-induced neuronal cell apoptosis

Purpose: To study the effects of icariin and quercetin on cell apoptotic changes in neurons induced by elevated glucose condition, and the mechanism involved. Methods: Neonatal male Sprague Dawley rats (n = 48) weighing 5 – 7 g were used. Neuronal cells were isolated from rat hippocampus and cultured after purification. The cells were randomly assigned to six groups: control, high glucose, icariin, quercetin, serine/threonine-specific protein kinase (Akt) inhibitor, and Akt agonist groups. The Akt inhibitor and agonist used in this study were MK-22062hci and SC79, respectively. The influence of icariin and quercetin on neuronal apoptotic changes were determined flow cytometrically, while their effects on levels of expression of Akt, p-Akt, bax and bcl-2 were determined with Western blotting. Results: Treatment with icariin or quercetin significantly inhibited apoptosis induced by high glucose. The concentrations of Akt, p-Akt, and bcl-2 proteins were markedly upregulated in high glucose group, relative to control (p < 0.05). The corresponding expression of bax was significantly down-regulated in high glucose group, relative to control (p < 0.05). Treatment with icariin or quercetin, or their agonists reversed high glucose-mediated alterations in these protein levels (p < 0.05). Conclusion: Icariin and quercetin inhibit neuronal cell apoptosis induced by high glucose through upregulation of bcl-2 expression and down- regulations of bax expression and Akt-induced protein phosphorylation. Thus, Icariin and quercetin possess potential benefits for the treatment of neurological diseases. Keywords: Apoptosis, High glucose condition, Hippocampal neurons, Icariin, Quercetin

Relating Factors for Impaired Fasting Glucose in Korean Adult: A Population Based Study

Background: Individuals with impaired fasting glucose who have poor health behaviors are at a greater risk for a variety of health outcomes. This study aimed to investigate the relationship between health literacy and health behaviors in Korean adults with impaired fasting glucose (IFG). Methods: This study adopted a secondary data analysis of the Korea National Health and Nutrition Examination Survey (KNHANES), which used a stratified, multi-stage, cluster-sampling design to obtain a nationally representative sample. This study analyzed the KNANES Health Examination Survey and Health Behavior Survey from 2016 to 2018. Multiple logistic regression analysis was employed to compute the odds ratios of health behaviors and health literacy to identify the risk factors for impaired fasting glucose.Results: Among the 9919 participants, 7093 (71.5%) were in the normal fasting glucose group and 2826 (28.5%) were in the impaired fasting glucose group. The presence of an impaired fasting glucose level varied significantly by sex, age, economic status, and whether participants dined out regularly, drank alcohol regularly, recognized nutrition fact labels, and utilized nutrition facts labels.Conclusions: Individuals with impaired fasting glucose were less likely to practice health behaviors and had lower health literacy compared with those with non-impaired fasting glucose. Our results suggest that improving health literacy in subjects with impaired fasting glucose is effective in improving their health behaviors.

Higher blood glucose impairs cardiac autonomic modulation in fasting and after carbohydrate overload in adults

This study aimed to assess whether the blood glucose levels influence cardiac autonomic modulation under fasting and after carbohydrate overload conditions. Participants (n=108) were separated into lower blood glucose and higher blood glucose groups, based on the median (90.5 mg•dL-1) of fasting glucose assessed. The SD2, SDNN, LF indices, and LF/HF increased, and HF decreased after dextrose overload compared to fasting (p<0.05). Body mass (78.9 vs 69.7 kg), abdominal circumference (90.2 vs 82.2 cm), systolic (113 vs 108 mmHg) and diastolic (72 vs 67 mmHg) blood pressure were higher (p < 0.05) in the higher blood glucose group. Heart rate variability (HRV) indices (SD1: 21.0 vs 26.5; SD2: 76.8: vs 86.1; RMSSD: 28.7 vs 37.5; SDNN: 56.1 vs 62.5 ms; pNN50: 10.6 vs 18.9%, HF: 328.4 vs 506.0; LF: 982.8 vs 1259.0 ms2), and the area under the curve of these indices after dextrose overload were lower in the higher blood glucose group (p < 0.05). Additionally, glycemia after dextrose overload was correlated with HRV indices (Rho = – 0.216 to – 0.273, p < 0.05). Individuals with higher blood glucose, even in the normality range, showed impairment in the cardiac autonomic modulation both at fasting and after carbohydrate overload. Novelty: - Higher fasting blood glucose impairs cardiac autonomic modulation - Carbohydrate overload impairs cardiac autonomic modulation

Effect of Insulin-Like Growth Factor-1 on Bone Formation of Bone Marrow Mesenchymal Stem Cells Under High Glucose Environment by Regulating Insulin Like Growth Factor Binding Protein 2(IGFBP-2)/p38 Pathway

Diabetes easily affects the biological properties of bone marrow mesenchymal stem cells (BMSCs). Insulin-like growth factor-1 (IGF-1) promotes bone healing during osteoporotic fractures. However, IGF-1's effect on BMSCs high glucose is unclear. Rat BMSCs were assigned into control group, high glucose group, and IGF-1 group in which BMSCs were transfected with pc-DNA 3.1-IGF-1 plasmid on the basis of high glucose followed by analysis of IGF-1, RUNX2 and OPN mRNA level by real time PCR, cell proliferation by MTT assay, alkaline phosphatase (ALP) activity, IGFBP-2 level by ELISA, and p38 phosphorylation by Western blot. High glucose group showed significantly decreased IGF-1, RUNX2 and OPN mRNA level, reduced ALP activity, IGFBP-2 expression and p38 phosphorylation compared to control group (P < 0 05). Transfection of IGF-1 plasmid under high-glucose environment significantly upregulated IGF-1, RUNX2 and OPN mRNA, increased ALP activity, IGFBP-2 expression and p38 phosphorylation compared to high-glucose group (P < 0 05). IGF-1 expression is reduced in high glucose environment. Up-regulation of IGF-1 can promote BMSCs osteogenic differentiation through the IGFBP-2/p38 pathway.