Expression Levels Of Glucose Transporter Research Articles

MiRNA-10a promotes cancer cell proliferation in oral squamous cell carcinoma by upregulating GLUT1 and promoting glucose metabolism.

MicroRNA-10a (miRNA-10a) promotes lung cancer; however, to the best of our knowledge, its involvement in other cancer types is unknown. The present study aimed to investigate the role of miRNA-10a in oral cancer. Expression levels of miRNA-10a and glucose transporter 1 (GLUT1) in tumor tissues and adjacent healthy tissues obtained from patients with oral squamous cell carcinoma (OSCC) were detected by reverse transcription-quantitative polymerase chain reaction. Correlation analysis between the expression levels of miRNA-10a and GLUT1 was performed using Pearson's correlation coefficient. It was identified that miRNA-10a and GLUT1 were upregulated in tumor tissues compared with adjacent healthy tissues of patients with OSCC. Expression levels of miRNA-10a and GLUT1 were positively correlated in tumor tissues but not in adjacent healthy tissues. In addition, miRNA-10a overexpression promoted glucose uptake and upregulated GLUT1 in OSCC cells. Furthermore, GLUT1 overexpression promoted glucose uptake; however, no significant increase in the expression level of miRNA-10a in OSCC cells was detected. Overexpression of miRNA-10a and GLUT1 promoted OSCC cell proliferation, while GLUT1-knockdown inhibited OSCC cell proliferation. GLUT1-knockdown also attenuated the enhancing effect of miRNA-10a overexpression on cancer cell proliferation. Therefore, miRNA-10a may promote cancer cell proliferation in OSCC by upregulating GLUT1 and promoting glucose metabolism.

Effect of MED28 and Vitamin D on Glycolytic Metabolism and Cell Growth in Human Colorectal Cancer Cells

Mammalian Mediator Complex has been implicated in human diseases, including cancer and metabolic disorder. MED28, a Mediator subunit, was found highly expressed in several types of cancer. Vitamin D, a secosteroid with hormone‐like features, exhibits multiple biological roles, including calcium homeostasis and cell differentiation. Calcitriol, 1,25‐dihydroxyvitamin D3, and its analogues have been suggested to suppress cancer development through vitamin D receptor (VDR). Our laboratory has previously reported that MED28 mediates Wnt/β‐catenin signaling and glucose metabolism in human colorectal cancer (CRC) cells, and we have also reported that calcitriol inhibits MED28‐mediated cellular events; in this study, we further examine their underlying mechanisms. First, by immunohistochemistry, we observed higher expression levels of MED28 in cancer tissues than those of adjacent normal counterparts in a CRC tissue microarray containing 19 paired tissue samples. Secondly, we detected lower protein expression of MED28, glucose transporter 1 (GLUT1), lactate dehydrogenase (LDHA), and cyclin D1, and less lactate production and higher pH value of the medium when we cultured human CRC cells in low glucose medium as compared with high glucose (25 mM) medium. Thirdly, the employment of siMED28 decreased both glucose uptake and lactate production, accompanied by lower expression levels of GLUT1 and LDHA as well as cyclin D1. Calcitriol inhibited the expression of MED28, and the effects of calcitriol on glucose metabolism and cell growth resembled those of MED28 suppression. In contrast, ectopic expression of MED28 increased glucose uptake as well as the protein expression of GLUT1, LDHA, and cyclin D1. Moreover, MED28 appeared to co‐localize and physically interact with VDR. Taken together, our findings indicated that MED28 upregulated Warburg effect and cell growth, including glucose uptake, lactate production, and the expression levels of GLUT1, LDHA, and cyclin D1, and calcitriol inhibited these events, where the interaction of MED28 and VDR may be responsible for the suppressive effect of calcitriol on MED28.Support or Funding InformationThis work was supported by the grant MOST 106‐2320‐B‐039‐062‐MY3 to M‐F Lee.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Additional effects of duodenojejunal bypass on glucose metabolism in a rat model of sleeve gastrectomy.

Sleeve gastrectomy with duodenojejunal bypass (SG-DJB) is expected to become a popular procedure in East Asia. The aim of this study was to evaluate the effects of duodenojejunal bypass on glucose metabolism in a rat model of sleeve gastrectomy (SG). Twenty-four Sprague-Dawley rats were divided into two groups: SG-DJB and SG alone. 6 weeks after surgery, body weight, feed intake, and metabolic parameters were measured, and oral glucose tolerance tests (OGTT) were performed. The mRNA expression of factors related to gluconeogenesis and glucose transport was evaluated using jejunal samples. Protein expression of factors with significantly different mRNA expression levels was evaluated using immunohistochemistry. Body weight and metabolic parameters did not significantly differ between the two groups. During the OGTT, the SG-DJB group showed an early increase in serum insulin followed by an early decrease in blood glucose compared with the SG group. Expression levels of glucose transporter 1 (GLUT1) and sodium-glucose cotransporter 1 (SGLT1) mRNA and protein in the alimentary limb (AL) were greater in the SG-DJB group than in the SG group. The additional effects of duodenojejunal bypass on glucose metabolism after SG may be related to increased expression of GLUT1 and SGLT1 in the AL.

Glucose-linked sub-50-nm unimer polyion complex-assembled gold nanoparticles for targeted siRNA delivery to glucose transporter 1-overexpressing breast cancer stem-like cells

Cancer stem-like cells (CSCs) treatment is a plausible strategy for enhanced cancer therapy. Here we report a glucose-installed sub-50-nm nanocarrier for the targeted delivery of small interfering RNA (siRNA) to CSCs through selective recognition of the glucose ligand to the glucose transporter 1 (GLUT1) overexpressed on the CSC surface. The siRNA nanocarrier was constructed via a two-step assembling process. First, a glucose-installed poly(ethylene glycol)-block-poly(l-lysine) modified with lipoic acid (LA) at the ω-end (Glu-PEG-PLL-LA) was associated with a single siRNA to form a unimer polyion complex (uPIC). Second, a 20 nm gold nanoparticle (AuNP) was decorated with ~65 uPICs through AuS bonding. The glucose-installed targeted nanoparticles (Glu-NPs) exhibited higher cellular uptake of siRNA payloads in a spheroid breast cancer (MBA-MB-231) cell culture compared with glucose-unconjugated control nanoparticles (MeO-NPs). Notably, the Glu-NPs became more efficiently internalized into the CSC fraction, which was defined by aldehyde dehydrogenase (ALDH) activity assay, than the other fractions, probably due to the higher GLUT1 expression level on the CSCs. The Glu-NPs elicited significantly enhanced gene silencing in a CSC-rich orthotopic MDA-MB-231 tumor tissue following systemic administration to tumor-bearing mice. Ultimately, the repeated administrations of polo-like kinase 1 (PLK1) siRNA-loaded Glu-NPs significantly suppressed the growth of orthotopic MDA-MB-231 tumors. These results demonstrate that Glu-NP is a promising nanocarrier design for CSC-targeted cancer treatment.

Inhibition of microRNA-218 promotes oral squamous cell carcinoma growth by targeting GLUT1 to affect glucose metabolism.

Glucose transporter 1 (GLUT1) is a key player in glucose metabolism that has important roles in oral squamous cell carcinoma (OSCC), while microRNA-218 can target GLUT1 to achieve its biological roles. Therefore, we hypothesize that microRNA-218 may target GLUT1 to participate in OSCC. Tumor tissues and adjacent healthy tissues were collected from OSCC patients, and blood samples were collected from both OSCC patients and healthy controls. Expression of microRNA-218 and GLUT1 in those tissues was detected by qRT-PCR. All patients were followed up for 5 years. Diagnostic and prognostic values of serum microRNA-218 for OSCC were investigated by ROC curve analysis and survival curve analysis, respectively. MicroRNA-218 knockdown OSCC cell lines were established. The effects on cell proliferation, glucose uptake as well as GLUT1 expression were detected by CCK-8 assay, glucose uptake assay and Western blot. MicroRNA-218 expression level was decreased while GLUT1 expression level was increased in tumor tissues compared with adjacent healthy tissues. Serum level of microRNA-218 was lower, while serum level of GLUT1 was higher in cancer patients than that in healthy control. Serum microRNA-218 and GLUT1 can be used to accurately predict OSCC and its prognosis. MicroRNA-218 knockdown promoted tumor cell proliferation, increased glucose uptake and promoted GLUT1 expression. Inhibition of microRNA-218 can promote oral cancer cell growth by targeting GLUT1 to affect glucose metabolism.

Regulatory effects of brown adipose tissue thermogenesis on maternal metabolic adaptation, placental efficiency, and fetal growth in mice.

To determine the role of UCP1-mediated thermogenesis in controlling maternal metabolic adaptation to pregnancy, energy metabolism of C57BL/6 wild-type (WT) and Ucp1 gene knockout ( Ucp1-/-) mice was studied during pregnancy. With the progression of pregnancy, maternal energy expenditure rates (EERs), expression of UCP1, and core body temperature steadily declined in WT dams. Despite no significant alterations in core body temperature and weight gain during pregnancy, Ucp1-/- dams exhibited lower rates in EER decline. High-fat (HF) feeding not only robustly increased maternal UCP1 expression and core body temperature but also abolished gestation-suppressed EER in WT dams. However, HF-increased EERs were significantly attenuated in Ucp1-/- dams. Significantly increased fetal body weights and fetal/placental weight ratio were detected in fetuses from Ucp1-/- dams compared with fetuses from WT dams. Markedly increased expression levels of glucose transporter 1 and amino acid transporters were also observed in placentas from Ucp1-/- dams. Furthermore, blood glucose concentrations of fetuses from Ucp1-/- dams were significantly higher than those of fetuses from WT dams, indicating that maternal UCP1 has an inhibitory effect on placental efficiency and fetal growth. Taken all together, this study demonstrated that maternal brown adipose tissue plays an important role in controlling maternal metabolic adaptation and placental nutrient transport.

2-(4-Methoxyphenyl)ethyl-2-Acetamido-2-deoxy-β-d-pyranoside (A Salidroside Analog) Confers Neuroprotection with a Wide Therapeutic Window by Regulating Local Glucose Metabolism in a Rat Model of Cerebral Ischemic Injury

2-(4-Methoxyphenyl)ethyl-2-acetamido-2-deoxy-β-d-pyranoside (salidroside analog-4g, SalA-4g), has shown neuroprotective prospects for the treatment of ischemic stroke. However, the dose–response and time window study for SalA-4g, and the mechanism of SalA-4g-mediated neuroprotection remain unclear. Here, we systematically investigated the therapeutic time window and dosage of SalA-4g in permanent focal cerebral ischemia in rats. SalA-4g dose-dependently improved stroke outcome. Either pre-treatment or post-treatment of SalA-4g exhibited notable neuroprotection, and maintained for up to 6 h after ischemia onset. Moreover, significant neurological functional recovery was found after SalA-4g administration in long-term functional assays. Further studies suggested that SalA-4g ameliorated neuronal cell death, elevated local glucose metabolism and enhanced the expression level of glucose transporter 1 and 3 in the ipsilateral cortex and striatum. We suggest that data of this study are critical in exploring the clinical application prospects of SalA-4g for the treatment of ischemic stroke.

Evaluation of aberrant metabolism related proteins in oral submucous fibrosis: A pilot study

ObjectivesThe mortality rate within five years of diagnosis is very high (>60%) for patients with oral cancer (OC), primarily due to late stage detection. Oral submucous fibrosis (OSF) is a heterogeneous oral lesion that has a high probability of developing into OC. One of the hallmark characteristics of malignant cells is alteration of metabolic pathways as the disease progresses towards carcinogenesis. This study aims to examine the altered metabolism-related proteins using immunohistochemistry (IHC). MethodsThe expression levels of glucose transporter 1 (GLUT1), hexokinase 2 (HK2), and fatty acid synthase (FASN) were analyzed in normal oral mucosa (NOM) (n = 30) and oral sub mucous fibrosis (OSF) (n = 30) using IHC. The degree of intensity and distribution of immunostaining was semi-quantitatively assessed. ResultsThe expression levels of GLUT-1, HK 2, and FASN were higher in the OSF group (p < 0.001) than in NOM control group. ConclusionsThese results indicate evidence of increased levels and alteration in the expression of metabolism-related proteins. Overexpression of these proteins may play an oncogenic role in the proliferative processes and disease progression of OSF. These results serve as a fundamental base for employing these proteins in future clinical applications.

Antidiabetic and antihyperlipidemic effects of the flower extract of Eriobotrya japonica in streptozotocin-induced diabetic mice and the potential bioactive constituents in vitro

This study was designed to evaluate the effects of flower extracts of Eriobotrya japonica (EJ) on diabetes and hyperlipidemia for 4 weeks in streptozotocin (STZ)-induced diabetic mice. EJ treatment significantly lowered levels of blood glucose, HbA1C, plasma triglyceride (TG), and total cholesterol (TC) but increased the size of the islets of Langerhans within the pancreas. Membrane expression levels of glucose transporter 4 (GLUT4) and phospho-Akt in the skeletal muscles from EJ-treated STZ mice were increased, but G6Pase mRNA levels were decreased, contributing to EJ’s antidiabetic activity. EJ caused an increase in hepatic expression of peroxisome proliferator-activated receptor α (PPARα) but a decrease in lipogenic FAS and mRNA levels of SREBP2, which decreased plasma TG and TC levels. One explanation for EJ’s antidiabetic and hypolipidemic activity is that tormentic acid represents the major component of EJ. These findings support the amelioration of the diabetic and dyslipidemic state by EJ in STZ-induced diabetic mice.

Glycolysis is essential for chemoresistance induced by transient receptor potential channel C5 in colorectal cancer

BackgroundElevated intracellular Ca2+ ([Ca2+]i) level could lead to [Ca2+]i overload and promote apoptosis via different pathways. In our previously study, up-regulated expression of transient receptor potential canonical channel (TRPC5) was proven to increase [Ca2+]i level, and resulted in chemoresistance whereas not apoptosis in human colorectal cancer (CRC) cells. The ATP-dependent homeostatic maintenance of resting [Ca2+]i should be important in this process. Increased glycolysis was found to be an important adenosine triphosphate (ATP) source in cancer. This study aimed to explore the potential mechanism of aerobic glycolysis in transient receptor potential channel TRPC5 induced chemoresistance.MethodsIn this study, we examined glucose transporter 1 (GLUT1) expression, glucose consumption and celluar ATP production to determine glycolytic activity. Real-time PCR and western blot were analyzed to determine TRPC5 expression at the mRNA and protein levels in human CRC cells (HCT-8, LoVo), and fluorouracil (5-Fu) resistant CRC cells (HCT-8/5-Fu, LoVo/5-Fu). 3-bromopyruvate (3-BP) and 2-Deoxy-D-glucose (2DG) were used to inhibit glycolysis. Glycolytic activity, intracellular Ca2+ ([Ca2+]i) and the half maximal inhibitory concentration of 5-Fu (5-Fu IC50) were measured. Western blot was analyzed to determine cleaved Caspase-3 protein level. Flow cytometry was performed to detect the apoptosis rates. Immunohistochemistry staining was performed to determine TRPC5 and GLUT1 expression level in human CRC tissues.ResultsOverproduced of TRPC5 and increased glycolysis were found in HCT-8/5-Fu and LoVo/5-Fu than in HCT-8 and LoVo cells. Compared to HCT-8 cells, the HCT-8/5-Fu cells showed higher [Ca2+]i levels which decreased after treated with TRPC5-specific shRNA. Furthemore, inhibition of glycolysis resulted in decreased ATP production, elevation of [Ca2+]i level and cleaved caspase-3, increased apoptotic cells rate, and a remarkable reversal of 5-Fu resistance in HCT-8/5-Fu cells, while showed no effect in HCT-8 cells. BAPTA-AM, a [Ca2+]i chelator, could reduce the elevation of cleaved caspase-3 and increased apoptotic cells rate due to glycolysis inhibition. Advanced CRC patients with high expression of TRPC5/GLUT1 displayed poorer chemotherapy outcome, and notably, the significant association between high TRPC5 expression and chemoresistance is GLUT1 expression level dependent.ConclusionsWe demonstrated the essential role of glycolysis in TRPC5 induced chemoresistance in human CRC cells via maintaining [Ca2+]i homeostasis.

Associations Between PET Textural Features and GLUT1 Expression, and the Prognostic Significance of Textural Features in Lung Adenocarcinoma.

We evaluated the association between positron emission tomography (PET) textural features and glucose transporter 1 (GLUT1) expression level and further investigated the prognostic significance of textural features in lung adenocarcinoma. We evaluated 105 adenocarcinoma patients. We extracted texture-based PET parameters of primary tumors. Conventional PET parameters were also measured. The relationships between PET parameters and GLUT1 expression levels were evaluated. The association between PET parameters and overall survival (OS) was assessed using Cox's proportional hazard regression models. In terms of PET textural features, tumors expressing high levels of GLUT1 exhibited significantly lower coarseness, contrast, complexity, and strength, but significantly higher busyness. On univariate analysis, the metabolic tumor volume, total lesion glycolysis, contrast, busyness, complexity, and strength were significant predictors of OS. Multivariate analysis showed that lower complexity (HR=2.017, 95%CI=1.032-3.942, p=0.040) was independently associated with poorer survival. PET textural features may aid risk stratification in lung adenocarcinoma patients.

Expression Changes in Lactate and Glucose Metabolism and Associated Transporters in Basal Ganglia following Hypoxic-Ischemic Reperfusion Injury in Piglets.

The neonatal brain has active energy metabolism, and glucose oxidation is the major energy source of brain tissue. Lactate is produced by astrocytes and released to neurons. In the central nervous system, lactate is transported between neurons and astrocytes via the astrocyte-neuron lactate shuttle. The aim of this study was to investigate the regulatory mechanisms of energy metabolism in neurons and astrocytes in the basal ganglia of a neonatal hypoxic-ischemic brain injury piglet model. A total of 35 healthy piglets (3-5 days of age; 1.0-1.5 kg) were assigned to a control group (n = 5) or a hypoxic-ischemic model group (n = 30). The hypoxic-ischemic model group was further divided into 6 groups according to the 1H-MR spectroscopy and PET/CT scan times after hypoxia-ischemia (0-2, 2-6, 6-12, 12-24, 24-48, and 48-72 hours; n = 5/group). 1H-MR spectroscopy data were processed with LCModel software. Maximum standard uptake values refer to the maximum standard uptake values for glucose (or FDG). The maximum standard uptake values of the basal ganglia-to-occipital cortex ratio were analyzed. The expression levels of glucose transporters and monocarboxylate transporters were detected by immunohistochemical analysis. Lactate levels decreased after an initial increase, with the maximal level occurring around 2-6 hours following hypoxia-ischemia. After hypoxia-ischemia, the maximum standard uptake values of the basal ganglia and basal ganglia/occipital cortex initially increased then decreased, with the maximum occurring at approximately 6-12 hours. The lactate and glucose uptake (basal ganglia/occipital cortex maximum standard uptake values) levels were positively correlated. The expression levels of glucose transporter-1 and glucose transporter-3 were positively correlated with the basal ganglia/occipital cortex. The expression levels of monocarboxylic acid transporter-2 and monocarboxylic acid transporter-4 were positively correlated with lactate content. The results indicate that lactate and glucose transporters have a synergistic effect on the energy metabolism of neurons and astrocytes following hypoxic-ischemic reperfusion brain injury.

Effect of Non-Starch Polysaccharide (NSP) of Wheat and Barley Supplemented with Exogenous Enzyme Blend on Growth Performance, Gut Microbial, Pancreatic Enzyme Activities, Expression of Glucose Transporter (SGLT1) and Mucin Producer (MUC2) Genes of Broiler Chickens

ABSTRACT The experiment was carried out in a completely randomized design (CRD) with 625 broiler chicks (Ross 308) for 5 repetitions (25 birds per each replicated) on the 5 treatments diet. Treatments included two different types of cereal grains (wheat, and barley) with or without an enzyme supplementation along with a corn-based diet as control group. The experimental diets were formulated to have similar contents of crude protein, metabolizable energy, total non-starch polysaccharides (NSP) and were fed in two periods of starter and grower. Experimental traits were consisted growth performance, ileal flora numeration, villus morphology in 3 parts of the intestine, digesta viscosity and pancreatic enzyme activity, and determining the gene expression level of glucose transporter (SGLT1) and mucin producer (MUC2) in the jejunum. Results indicated that inclusion of wheat and barley to corn-soy based diet with or without exo-enzymes blend on growth performance traits were significant (p<0.01). Feed intake and average daily gain in wheat diet was lower, conversely FCR was higher than other groups (p<0.01). Maximum microbial count were observed in wheat and barley diets and minimum were observed in enzyme supplemented diets respectively (p<0.01). Control group and enzyme supplemented diets had minimum counting of gram negative, coliform and clostridium, but maximum counting of lactobacilli and bifidobacter were observed in enzyme supplemented diets (p<0.01). Viscosity and activities of pancreatic a-amylase and lipase were significantly increased in chicks fed wheat and barley when compared to the control group fed on corn (p<0.01). Feeding wheat and barley diets reduced villus height in different parts of the small intestine when compared to those fed on a corn diet (p<0.01). Gene expression level of glucose transporter (SGLT1) and mucin producer (MUC2) in jejunum was significantly affected by the inclusion of wheat and barley to corn-soy based diet with or without exo-enzymes blend (p<0.01). In conclusion, the inclusion of wheat and barley to corn-soy based diet without enzyme supplementation has an adverse effect on growth, ileal microflora villi morphology, digesta viscosity, pancreatic enzyme activity, and gene expression level of nutrient transporters. However, enzyme supplemented to wheat and barley diets significantly improved those traits, and restored the negative effects.

Curcumin improves diabetes mellitus‑associated cerebral infarction by increasing the expression of GLUT1 and GLUT3.

Curcumin is characterized by anti‑inflammatory, anti‑oxidative, antiviral, antifibrotic, anticoagulation and glucose regulatory functions. However, whether it is protective in diabetes mellitus‑associated cerebral infarction remains to be fully elucidated. In the present study, it was demonstrated for the first time, to the best of our knowledge, that curcumin markedly improved neurological deficits, cerebral infarct volume and brain edema rate following middle cerebral artery occlusion (MCAO) surgery. It was also shown that the expression levels of glucose transporter (GLUT)1 and GLUT3 were reduced in the MCAO group. However, following curcumin treatment, the levels of GLUT1 and GLUT3 were markedly increased. In addition, curcumin markedly decreased cell apoptosis, indicating an anti‑apoptotic role of curcumin in the brain. To further evaluate whether curcumin prevented cell apoptosis by modulating the expression of GLUT1 and GLUT3, small interfering RNAs targeting GLUT1 and GLUT3 were selected. It was found that the knockdown of GLUT1 and GLUT3 inhibited the abundance of GLUT1, GLUT3 and B‑cell lymphoma 2, even following incubation with curcumin. These data showed that curcumin protected brain cells from apoptosis and cerebral infarction, predominantly by upregulating GLUT1 and GLUT3.

GLUT1 regulates cell glycolysis and proliferation in prostate cancer.

Glucose transporter 1 (GLUT1) plays a critical role in tumorigenesis and tumor progression in multiple cancer types. However, the specific function and clinical significance of GLUT1 in prostate cancer (PCa) are still unclear. Therefore, in this study, we investigated the role of GLUT1 in PCa. GLUT1 protein levels in prostate cancer tissue and tumor-adjacent normal tissues were measured and compared. Furthermore, real-time PCR and Western blot analysis were both used to detect GLUT1 expression levels in different PCa cell lines. Flow cytometry and cell-based assays, such as a glucose uptake and lactate secretion assay, CCK-8 assay, and transwell migration and wound healing assay, were used to monitor cancer cell cycle distribution, glycolysis, proliferation, and motility, respectively. Moreover, a mouse tumor xenograft model was used to investigate the role of GLUT1 in tumor progression in vivo. GLUT1 expression levels are higher in PCa tissues than in tumor-adjacent normal tissues. The results from real-time PCR and Western blot analysis revealed a similar increase in the GLUT1 expression levels in PCa cell lines. Moreover, knockdown of GLUT1 inhibits cell glycolysis and proliferation and leads to cell cycle arrest at G2/M phase in the 22RV1 cell line but not in the PC3 cell line. In vivo experiments further confirmed that GLUT1 knockdown inhibits the growth of tumors derived from the 22RV1 cell line. In addition, we also showed that GLUT1 knockdown has no effect on cell migration in vitro. GLUT1 may play an important role in PCa progression via mediating glycolysis and proliferation. Our study also indicated a potential crosstalk between GLUT1-mediated glycolysis and androgen sensitivity in PCa.

The anti-hyperuricemic effect of epigallocatechin-3-gallate (EGCG) on hyperuricemic mice

Epigallocatechin-3-gallate (EGCG), a major constituent of green tea catechin, has been used for antioxidant. This study aimed to evaluate the antihyperuricemic activity of EGCG on hyperuricemic mice. We demonstrated that serum uric acid (UA) level was decreased significantly with dose-dependence by EGCG treated with 10, 20, and 50mg/kg. Compared with the model, data on blood urea nitrogen (BUN) supported that there was significance with high dose of EGCG (50mg/kg). Levels of serum creatinine (Cr) in each EGCG-treated group were decreased but not significant; the activities of hepatic xanthine oxidase (XOD) and adenosine deaminase (ADA) in high dose groups' EGCG were notably lower than those of model group. EGCG could downregulate the renal mRNA expression levels of glucose transporter 9 (GLUT9) and urate transporter 1 (URAT1) on hyperuricemic mice. These results presented that EGCG had obvious hypouricemic and renal protective effects on hyperuricemic mice. Our data may have a potential value in clinical practice in the treatment of hyperuricemia.

18F-fluorodeoxyglucose uptake predicts MET expression in lung adenocarcinoma.

ObjectiveMET is a member of the receptor tyrosine kinases. Several MET-targeting inhibitors and antagonistic antibodies have shown promising data in clinical trials of lung adenocarcinoma. Finding noninvasive diagnostic tools to estimate the status of MET is helpful in clinical practice. 18F-fluorodeoxyglucose positron emission tomography/computerized tomography (18F-FDG PET/CT) has been used routinely for the diagnosis and staging of tumors. However, the relationship between MET expression and 18F-FDG uptake has not been investigated yet. This study aimed to determine the correlation of MET expression with 18F-FDG uptake on PET-CT scan and whether or not 18F-FDG PET/CT can be used to predict the MET status of lung adenocarcinoma patients.Patients and methodsFifty-seven lung adenocarcinoma patients were analyzed in our study. Maximum standardized uptake value (SUVmax) was calculated in all PET/CT images. The expression levels of MET and two important glycolysis-related markers, glucose transporter 1 (GLUT1) and pyruvate kinase M2, were analyzed by immunohistochemistry of tissues. Spearman rank correlation was used to analyze the association between MET expression and SUVmax. In vitro MET knockdown in lung adenocarcinoma cells was used to examine the role of MET in tumor metabolism. The effect of MET on GLUT1 expression was investigated using Western blot assay and quantitative polymerase chain reaction.ResultsSUVmax was positively correlated with the expression levels of MET (r=0.458; P<0.001) and GLUT1 (r=0.551; P<0.001). SUVmax was significantly higher in patients with positive MET expression than in those with negative MET expression (9.92±6.62 vs 4.60±3.00; P=0.002). MET knockdown in lung adenocarcinoma cells led to a significant decrease in GLUT1 expression and 18F-FDG uptake.ConclusionMET could increase 18F-FDG uptake by upregulating GLUT1 expression. 18F-FDG PET/CT could be used to predict the MET status of lung adenocarcinoma patients and to supply valuable information to guide targeted therapy.

Mesenchymal stromal cells isolated from gestationally diabetic human placenta exhibit insulin resistance, decreased clonogenicity and angiogenesis

Pregnancy is known to be a diabetogenic state. With sedentary lifestyle and wrong dietary choices, gestational diabetes mellitus is on the rise. This raises a concern as placenta is becoming an acceptable choice, as a source of Mesenchymal Stromal Cells (MSCs). In our current study we questioned whether there exists a difference between MSCs isolated from normal and diabetic (Gd-P-MSCs) placenta, as the health of the cells used in therapy is of prime importance. We isolated and verified the Gd-P-MSCs based on their surface markers and differentiation potential. We looked at viability and proliferation and did not see a difference between the two. We analysed the glucose uptake potential of these cells by assessing the remnant glucose in the media, glucose within the cells by 2-NBDG and by glycogen storage. Despite only a slight downregulation of mRNA expression levels of glucose transporters, Gd-P-MSCs exhibited decreased glucose uptake even upon insulin stimulation and decreased glycogen storage, indicative of an insulin resistant state. We then assessed the colony forming ability of the cells and found a decreased clonogenicity in Gd-P-MSCs. We also examined the angiogenic potential of the cells by tube formation. Gd-P-MSCs showed decreased angiogenic potential when compared to normal cells. Thus we show for the first time, the effect of gestational diabetes on cells isolated from the chorionic villi of term placenta. Gd-P-MSCs are indeed insulin resistant, exhibit decreased clonogenicity and angiogenic potential. The present investigation is of relevance to the choice of sample for MSC isolation for therapeutic purposes.

The Effects of Selenium Supplementation on Gene Expression Related to Insulin and Lipid in Infertile Polycystic Ovary Syndrome Women Candidate for In Vitro Fertilization: a Randomized, Double-Blind, Placebo-Controlled Trial.

http://www.irct.ir : IRCT201704245623N113.

Oncophosphosignaling Favors a Glycolytic Phenotype in Human Drug Resistant Leukemia.

In chemoresistant leukemia cells (Lucena-1), the low molecular weight protein tyrosine phosphatase (LMWPTP) is about 20-fold more active than in their susceptible counterpart (K562). We found this phosphatase ensures the activated statuses of Src and Bcr-Abl. Since, phosphorylation and dephosphorylation of proteins represent a key post-translational regulation of several enzymes, we also explored the kinome. We hereby show that LMWPTP superactivation, together with kinome reprogramming, cooperate towards glucose addiction. Resistant leukemia cells present lower levels of oxidative metabolism, in part due to downexpression of the following mitochondrial proteins: pyruvate dehydrogenase subunit alpha 1, succinate dehydrogenase, and voltage-dependent anion channel. Those cells displayed higher expression levels of glucose transporter 1 and higher production of lactate. In addition, Lucena-1 siRNA LMWPTP cells showed lower expression levels of glucose transporter 1 and lower activity of lactate dehydrogenase. On the other hand, K562 cells overexpressing LMWPTP presented higher expression/activity of both proteins. In this study, we show that LMWPTP is a pivotal mediator of metabolic reprogramming that confers survival advantages to leukemia cells against death stimuli. J. Cell. Biochem. 118: 3846-3854, 2017. © 2017 Wiley Periodicals, Inc.