Objective To summarize the advance of bioenergetic metabolic mechanisms of cancer cell. Methods Literatures about the recent studies on the bioenergetic metabolic mechanisms of cancer cell were reviewed.Results Cancer cells required a steady source of metabolic energy in order to continue their uncontrolled growth and proliferation. Accelerated uptake of glucose and glycolysis was one of the biochemical characteristics of hypoxia cancer cells. Glucose transport and metabolism were essential for the survival of tumor cells, leading to poor prognosis. Conclusions The studies on relationships between hypoxia-inducible genes and cancer have come a new understanding of the bioenergetic metabolic mechanisms of cancer cell, become new and important supplementary means of diagnosis and treatment of cancer, and enhanced existing strategies so that the treatment could be more rationally applied and personalized for cancer patients.
ObjectiveTo elucidate whether hypoxia induced factor-1α (HIF-1α) gene improved hypoxia tolerant capability of bone marrow mesenchymal stem cells uptake(MSCs) or not and whether the capability was related to glucose uptake increase in hypoxia MSCs ex vivo or not. MethodsMSCs were randomly divided into normoxia non-HIF-1α transfection group (control group), normoxia HIF-1α transfection group, hypoxia non-HIF-1α transfection group, and hypoxia HIF-1α transfection group and then each group was cultured with normoxia (5% CO2 at 37 ℃) or hypoxia (94% N2, 1% O2, 5% CO2 at 37 ℃) for 8 h, respectively. Finally, the expressions of HIF-1α were detected by immunocytochemistry, RT-PCR, and Western blot methods, respectively. Apoptosis ratio (AR) and death ratio (DR) were tested by flow cytometry. The proliferation was detected by MTT method. Glucose uptake was assayed by radiation isotope method. Results① Compared with the normoxia non-HIF-1α transfection group, the expression of HIF-1α mRNA significantly increased (Plt;0.01) in the normoxia HIF-1α transfection group except for its protein (P=0.187); Both of mRNA and protein expressions of HIF-1α in the hypoxia HIF-1α transfection group were significantly higher than those in the hypoxia non-HIF-1α transfection group (Plt;0.01). ② The AR (P=0.001) and DR (P=0.003) in the hypoxia HIF-1α transfection group were significantly lower thanthose in the hypoxia non-HIF-1α transfection group, both of which were significantly higher than those in the normoxia non-HIF-1α transfection group (Plt;0.01). ③ The proliferation of MSCs in the hypoxia HIF-1α transfection group was significantly higher than that in the hypoxia non-HIF-1α transfection group (P=0.004), which significantly lower than that in the normoxia non-HIF-1α transfection group (P=0.001). ④ Compared with the hypoxia non-HIF-1α transfection group, the 3H-G uptake capability (P=0.004) of MSCs significantly increased in the hypoxia HIF-1α transfection group, which was significantly lower than that in the normoxia non-HIF-1α transfection group (P=0.001). ⑤ There were significantly negative relation between AR and HIF-1α protein (r=-0.71,P=0.005) or 3H-G uptake (r=-0.65,P=0.004), and significantly positive relation between HIF-1α protein expression and 3H-G uptake (r=0.77, P=0.003). ConclusionHIF-1α gene significantly improves anti-hypoxia capability of MSCs, which is fulfilled by increasing glucose upake.
Objective To elucidate whether glucose transporters-4 (GLUT-4) takes part in glucose uptake of mesenchymal stem cells (MSCs) and whether Akt gene improves translocation and expression of GLUT-4 in MSCs under hypoxic environment ex vivo. Methods MSCs, transfected by Akt gene and no, were cultured with normoxia (5% CO2) or hypoxia (94%N2, 1%O2 and 5% CO2) at 37 ℃ for 8 h. Glucose uptake was assayed by using radiation isotope 2-[3H]-deoxy-Dglucose (3H-G) and the expression of GLUT-4 protein and mRNA was assayed by immunocytochemistry, Western blot and RT-PCR, respectively. Results ①3 H-G intake of MSCs was significantly increased in hypoxiatransfection group than that in hypoxia-non-transfection 〔(1.39±0.13) fold, P<0.05〕, but which was lower than that in normoxia-non-transfection group, P<0.05. ②GLUT-4 was expressed by MSCs under any conditions. Compared with normoxia-non-transfection group, hypoxia decreased the expressions of GLUT-4 mRNA and protein significantly (P<0.05). ③Compared with hypoxianontransfection group, the expression of GLUT-4 〔mRNA(1.756±0.152) fold, total protein in cell (1.653±0.312) fold, protein in plasma membrane (2.041±0.258) fold〕 was increased in hypoxia-transfection group significantly (P<0.05), but which was lower than that in normoxianontransfection group (P<0.05). ④There was significantly positive relation between 3H-G intake and GLUT-4 protein expression in plasma membrane (r=0.415, P=0.001).Conclusion GLUT-4 may take part in glucose uptake of MSCs, and the capability of Akt gene to improve MSCs anti-hypoxia may be finished by its role in increasing the expression and translocation of GLUT-4.
Objective To observe the effects of high concentr at ion glucose on the calcium-activated potassium channel of rabbits′ retinal Müller cells. Methods The rabbits′retinal Müller cells were cultured in vitro under the condition of high concentration glucose, and identified by immunohistochemical staining and transmission electron microscopy. Patch-clamp technique was used to observe the changes of the calcium-activated potassium channel of retinal Müller cells caused by high concentration glucose at different time.Results High concentration glucose could inhibit the calcium-activated potassium channel of cultured retinal Müller cells in a time-dependent manner. Conclusion High concentration glucose may reduce the biological functions of Müller cells by inhibiting calcium-activated potassium channel. (Chin J Ocul Fundus Dis,2003,19:164-167)
ObjectiveTo explore the expressions of glucose regulated protein (GRP) 78 and GRP94 in rectal adenocarcinoma and their clinical significances.
MethodsIn 45 paraffin-embedded sections of rectal adenocarcinoma tissues and adjacent normal tissues, the expressions of GRP78 and GRP94 were examined by EnVisionTM.
ResultsThe positive rates of GRP78 and GRP94 protein expression in the rectal adenocarcinoma tissues were 53.33% (24/45) and 53.33% (24/45), while those in the adjacent normal tissues were 13.33% (6/45) and 15.56% (7/45), respectively. There was a statistical significance of the expression of GRP78 or GRP94 between the tumor tissues and the adjacent normal tissues (all P < 0.001), and it was found that the positive expression rates were relevant to the extent of differentiation, Dukes stage, and lymph node metastasis of cancer (all P < 0.05), but not to the patient's sex, age, and size of tumor (all P > 0.05). And there was a statistical significance in Spearman method about the rate of positive expression between GRP78 and GRP94 (rs=0.464, P < 0.01).
ConclusionGRP78 and GRP94 protein is highly expressed in rectal adenocarcinoma tissue, related to its metastasis and invasion, might be used as a useful indicator to judge the malignant degree.
ObjectiveTo systematically review the intervention efficacy of resistance exercise on prediabetes and type 2 diabetes. MethodsPubMed, The Cochrane Library, EMbase, Web of Science, EBSCO, VIP, WanFang Data and CNKI databases were electronically searched to collect randomized controlled trials (RCTs) of resistance exercise applied to pre-diabetic and type 2 diabetic population from 2010 to April, 2021. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Meta-analysis was then performed using Revman 5.1 and Stata 12.0 software. ResultsA total of 26 RCTs involving 2 078 patients were included. The results of meta-analysis showed that resistance exercise could improve fasting blood glucose (MD=?0.57, 95%CI ?0.69 to ?0.45, P<0.000 01), glycosylated hemoglobin (MD=?0.28, 95%CI ?0.33 to ?0.22, P<0.000 01), high density lipoprotein (MD=0.06, 95%CI 0.01 to 0.11, P=0.01), low density lipoprotein (MD=?0.35, 95%CI ?0.47 to ?0.24 , P<0.000 01), total cholesterol (MD=?0.25, 95%CI ?0.39 to ?0.12, P=0.000 3), steady-state model-insulin resistance index (MD=?0.74, 95%CI ?0.80 to ?0.68, P<0.000 01), and body mass index (MD=?0.54, 95%CI ?1.03 to ?0.05, P=0.03) compared with control group. ConclusionsResistance exercise can improve the blood glucose, blood lipid, and insulin resistance levels of individuals with abnormal glucose and lipid metabolism. Due to limited quality and quantity of the included studies, more high-quality studies are required to verify above conclusions.
Objective To assess the differences between a glucose meter and autoanalyzer at home and broad.Method MEDLINE, CNKI, FMJS, and CBM were searched electronically (1995 to May, 2008). The statistical analysisof included studies was performed according to the Cochrane systematic reviews method. Result Twenty four studies, including 11 English records and 19 Chinese records involving 4 963 specimens, were included in this study. Meta-analysis showed us the blood glucose values of Abbott, Roche, and Johnson abroad subgroups are higher than the laboratory method, and their WMD (95%CI) are 0.57 (0.34,0.80), 0.43 (0.04,0.81), 0.41 (0.11,0.71). The blood glucose values of the Abbot and Roche domestic subgroups are comparable to the laboratory method [WMD= 0.60, 95%CI (– 0.79, 1.99); WMD= – 0.13, 95%CI (– 0.56, 0.29)]. The blood glucose value of the Johnson domestic subgroup is lower than laboratory method [WMD= – 0.95, 95%CI (– 1.42, – 0.48)]. Conclusion The results of the abroad studies are relatively consistent, and the blood glucose values of all abroad subgroups are higher than laboratory method. The domestic studies are different because of other factors.
Objective
To explore the relationship between obesity and the three targets including blood pressure, glucose, and lipid.
Methods
A total of 181 adult Tibetans who underwent physical examination between March and September 2015 at Xigaze People's Hospital were enrolled in this study. Their obesity degrees were assessed with body mass index (BMI) and waist circumference (WC) respectively. The levels of blood pressure, glucose, and lipid were compared at the different levels of BMI or WC.
Results
The incidence of systematic obesity and central obesity in these adults were 57.5% and 79.0%, respectively. Compared the overweight group with the normal BMI group, the systolic pressure and diastolic pressure of the former were 9.26 mm Hg (1 mm Hg=0.133 kPa) [95% confidence interval (CI) (3.46, 15.07) mm Hg, P=0.002] and 7.76 mm Hg [95%CI (3.96, 11.57) mm Hg, P<0.001] higher, respectively. Similarly, the systolic pressure and diastolic pressure of the central obesity group were 8.24 mm Hg [95%CI (1.03, 15.46) mm Hg,P=0.026] and 6.79 mm Hg [95%CI (2.03, 11.55) mm Hg, P=0.006] higher than those in the normal WC group, respectively. For the normal WC or normal BMI subjects, the detection rate of dyslipidemia reached up to 50.0% and 52.6%.
Conclusions
With the increase of BMI/WC values, the level of blood pressure rises. Even though WC or BMI is normal, the detection rate of dyslipidemia is high.
ObjectiveTo observe and analyze the correlation between time within target glucose range (TIR) and hemoglobin A1c (HbA1c) and the risk of diabetic retinopathy (DR). MethodsA retrospective clinical study. From March 2020 to August 2021, 91 patients with type 2 diabetes mellitus (T2DM) who were hospitalized in Department of Endocrinology and Metabolic Diseases, Affiliated Hospital of Weifang Medical University, were included in the study. All patients underwent Oburg's no-dilatation ultra-wide-angle laser scan ophthalmoscopy, HbA1c and continuous glucose monitoring (CGM) examinations. According to the examination results and combined with the clinical diagnostic criteria of DR, the patients were divided into non-DR (NDR) group and DR group, with 50 and 41 cases respectively. The retrospective CGM system was used to monitor the subcutaneous interstitial fluid glucose for 7 to 14 consecutive days, and the TIR was calculated. Binary logistic regression was used to analyze the correlation between TIR, HbAlc and DR in patients with T2DM0. At the same time, a new indicator was generated, the predicted probability value (PRE_1), which was generated to represent the combined indicator of TIR and HbA1c in predicting the occurrence of DR. The receiver operating characteristic curve (ROC curve) was used to analyze the value of TIR, HbAlc and PRE_1 in predicting the occurrence of DR. ResultsThe TIR of patients in the NDR group and DR group were (81.58±15.51)% and (67.27±22.09)%, respectively, and HbA1c were (8.03±2.16)% and (9.01±2.01)%, respectively. The differences in TIR and HbA1c between the two groups of patients were statistically significant (t=3.501,-2.208; P=0.001, 0.030). The results of binary logistic regression analysis showed that TIR, HbA1c and DR were significantly correlated (odds ratio=0.960, 1.254; P=0.002, 0.036). ROC curve analysis results showed that the area under the ROC curve (AUC) of TIR, HbA1c and PRE_1 predicting the risk of DR were 0.704, 0.668, and 0.707, respectively [95% confidence interval (CI) 0.597-0.812, P=0.001; 95%CI 0.558-0.778, P=0.006; 95%CI 0.602-0.798, P=0.001]. There was no statistically significant difference between TIR, HbA1c and PRE_1 predicting the AUC of DR risk (P>0.05). The linear equation between HbAlc and TIR was HbAlc (%) = 11.37-0.04×TIR (%). ConclusionsTIR and HbA1c are both related to DR and can predict the risk of DR. The combined use of the two does not improve the predictive value of DR. There is a linear correlation between TIR and HbAlc.
Objective To explore the effect of ghrelin on insulin secretion and expression of glucose transporter protein-2 (Glut-2) in isolated pancreas of rats. Methods Twenty five Wistar rats were randomly devided into normal control group (NC group), high concentration of glucose group (HCG group), high concentration of glucose with high concentration of ghrelin group (10-8mol/L, HCG+HCGh group), medium concentration of ghrelin group(10-9mol/L, HCG+MCGh group), and low concentration of ghrelin group (10-10mol/L, HCG+LCGh group) with 5 rats in each group. The rat isolated pancreas perfusion models were established firstly, then from the distal end of abdominal aortas, the models were perfused with low concentration of glucose (5.5mmol/L), high concentration of glucose (33.3mmol/L) or high concentration of glucose added with different concentrations of ghrelin. Levels of insulin outflowed from portal vein were tested by ELISA method, expression levels of Glut-2 protein were tested by immunohistochemical method,and ultrastructure changes of islet β cell were observed under the transmission electron microscope. Results There were no significant difference on levels of fasting blood glucose (FBG), fasting insulins (FINS), homeostasis model of assess-ment for insulin resistence index (HOMA-IR), and homeostasis model of assessment for pancreatic β cell function (HOMA-β),(P>0.05). There were no significant difference on insulin levels of effluent from portal vein of 5 groups (P>0.05) when isolated pancreas perfused with 5.5mmol/L glucose, while had 2 secretion peaks in 3min and 10-12min after 33.3 mmol/L glucose perfusion, where HCG+HCGh group at the top. The mean density value of Glut-2 protein in NC group was higher than that of other 4 groups (P<0.05). The results of transmission electron microscopy showed that apoptosis was lighter in NC group than that of other 4 groups, and apoptosis of HCG+HCGh group was lighter than that of HCG+MCGh group and HCG+LCGh group. Conclusions In isolated pancreas of rats, ghrelin promotes high concentration of glucose-stimulated insulin secretion, decreases expression of Glut-2 protein, and protects the islet β cell.