ABSTRACT
The study investigates the mechanism by which Peganum harmala L. (Luotuopeng, LTP) inhibits tube formation in retinal vascular endothelial cells. Tube formation was induced by treatment of retinal vascular endothelial cells with glucose. The cells were divided into a normal group, model group, and an LTP group. The total length of tube formation was measured. The active components, targets, and pathway by which LTP acts in the treatment of diabetic retinopathy was explored by network pharmacology. The mRNA expression levels of targets [extracellular signal-regulated kinase 2 (ERK2), phosphoinositide 3 kinase catalytic alpha polypeptide (PIK3CA), serine/threonine-protein kinase 1 (AKT1)] related to the mitogen-activated protein kinase (MAPK) signaling pathway and vascular endothelial growth factor (VEGF) signaling pathway was measured by real-time PCR. The results of tube formation indicated that compared with the normal group, the total tube length increased in the model group (P < 0.01); after the treatment with LTP, the total tube length decreased compared with the model group (P < 0.01). Network pharmacology revealed that the targets of LTP included PIK3CA, AKT1, and ERK2, and the pathways involved the MAPK signaling pathway and the VEGF signaling pathway. Real-time PCR indicated that compared with the normal group, the mRNA expression levels of ERK2, PIK3CA and AKT1 were elevated in the model group (P < 0.05); after treatment with LTP, the mRNA expression levels of ERK2, PIK3CA and AKT1 decreased compared with the model group (P < 0.05). LTP may inhibit retinal vascular endothelial cell tube formation by regulating the MAPK signaling pathway and the VEGF signaling pathway. This study confirms the multi-targets and multi-pathways of LTP and provides a basis for its use in the treatment of diabetic retinopathy．
ABSTRACT
<p><b>Background</b>Placebo was defined as any therapy that is used for its nonspecific psychological and physiologic effect but has no specific pharmacologic impact on the condition being treated. Besides medication therapies, studies have found that the optimal dietary approach as well as physical activity and education are useful to control hyperglycemia in patients with type 2 diabetes (T2DM). The aim of this study was to evaluate the placebo effects of antidiabetic therapies in Asian and Caucasian T2DM patients and make a comparison between the two ethnicities.</p><p><b>Methods</b>A search using the MEDLINE database, EMBASE, and Cochrane Database was performed, from when recording began until December 2016. The main concepts searched in English were sulfonylurea (SU); alpha glucosidase inhibitors (AGI); metformin (MET); thiazolidinediones (TZD); dipeptidyl peptidase-4 inhibitors (DPP-4i); sodium-glucose cotransporter 2 inhibitors (SGLT2i); glucagon-like peptide-1 receptor agonist (GLP-1RA); type 2 diabetes (T2DM); placebo controlled; and randomized controlled trials. Using the Cochrane instrument, we evaluated the adequacy of randomization, allocation concealment procedures, and blinding.</p><p><b>Results</b>This study included 63 studies with a total of 7096 Asian patients involved and 262 studies with a total of 27,477 Caucasian patients involved. In Caucasian population, the use of placebo led to significant reductions of glycosylated hemoglobin (HbA1c), -0.683% (P = 0.008) in SU monotherapy treatment, -0.193% (P = 0.001) in DPP-4i treatment, and -0.230% (P < 0.001) in SGLT2i treatment, respectively. In Asian population, the use of placebo resulted in significant decreases of HbA1c, -0.162% (P = 0.012) in DPP-4i treatment and -0.269% (P = 0.028) in GLP-1RA add-on therapy, respectively. The placebo also significantly reduced body weight. In Caucasian population, placebo use resulted in 0.833 kg (P = 0.006) weight loss by SU treatment and 0.953 kg (P = 0.006) weight loss by GLP-1RA treatment. In Asian population, the placebo led to a weight change of 0.612 kg (P < 0.001) by GLP-1RA analog treatment. The changes of HbA1c and weight due to the placebo effect in other treatments were not significant in both Asian and Caucasian population. Comparisons of the placebo effect on HbA1c change and weight change in each treatment group indicated that no significant difference was found between Asian and Caucasian population.</p><p><b>Conclusions</b>The overall differences of the placebo effect on HbA1c changes as well as on body weight changes were not significant between Asian and Caucasian T2DM patients. The placebo effect on HbA1c changes and weight changes was not associated with baseline age, gender, baseline body mass index, baseline HbA1c, duration of diabetes, or study duration.</p>
ABSTRACT
<p><b>OBJECTIVE</b>To study the expression of RAS protein in human glioma tissues and its influence on tumor growth.</p><p><b>METHODS</b>RAS protein expression in glioma tissues was determined by immunohistochemical (IHC) staining. Subsequently, MTT cell proliferation assay, flow cytometry and Western blotting were used to assay U251 cells with reduced RAS expression.</p><p><b>RESULTS</b>The expression of RAS in glioma was increased and strongly correlated with pathological grade. Downregulation of RAS resulted in glioma cells growth suppression and increased apoptosis.</p><p><b>CONCLUSION</b>The expression level of RAS protein in human glioma was increased. Downregulation of RAS can inhibit glioblastoma cell growth through the RAS signal pathway.</p>
Subject(s)
Humans , Brain Neoplasms , Genetics , Metabolism , Pathology , Cell Growth Processes , Genetics , Cell Line, Tumor , Down-Regulation , Glioma , Genetics , Pathology , Immunohistochemistry , ras Proteins , GeneticsABSTRACT
<p><b>BACKGROUND</b>Invasion growth is the most characteristic biological phenotype of glioblastoma, but the molecular mechanism in glioma cell invasion is poorly understood. Recent data have showed that microRNA plays an essential role in tumor invasion. Our study aimed to explore the mechanism of miR-7 involved in the control of glioblastoma cell invasion.</p><p><b>METHODS</b>Glioma cell invasion was evaluated by transwell and scratch assays after up-regulation of miR-7 using miR-7 mimics in U87 and U251 cells. Luciferase reporter assay was used to determine focal adhesion kinase (FAK) as a target of miR-7. The levels of miR-7, matrix metalloproteinases (MMP)-2 and MMP-9 mRNA were detected by PCR assay, and the levels of FAK, MMP-2, MMP-9, total and phosphorylation serine/threonine kinase (AKT), and extracellular signal-regulated kinase (ERK) 1/2 were measured by Western blotting analysis.</p><p><b>RESULTS</b>Over-expression of miR-7 inhibited the invasion and migration activity of U87 and U251 cells. And up-regulation of miR-7 reduced FAK protein expression, Further, luciferase reporter assay showed that miR-7 modulated FAK expression directly by binding 3'UTR of FAK mRNA. In addition, miR-7 repressed p-ERK1/2 and p-AKT level, MMP-2 and MMP-9 expression. Finally, the inverse relationship between FAK and miR-7 expression was certificated in human glioma tissues.</p><p><b>CONCLUSION</b>To our knowledge, these data indicate for the first time that miR-7 directly regulates cell invasion by targeting FAK in glioblastoma and that miR-7 could be a potential therapeutic target for glioblastoma intervention.</p>