Hyperglycemia causes increased protein glycation and the formation of early glycation products and advanced glycation end products (AGEs) which are major factors responsible for the complications associated with diabetes. The aim of the present study was to investigate the antioxidant as well as antiglycative potential of ethyl acetate fraction of guava leaves. Oral administration of the extract at different doses showed a significant decrease in blood glucose level. It also showed an improved antioxidant potential as evidenced by decreased lipid peroxidation and a significant increase in the activity of various antioxidant enzymes such as catalase, superoxide dismutase, glutathione peroxidase and glutathione reductase. Glycated hemoglobin as well as fructosamine which are indicators of glycation was also reduced significantly in treated groups when compared to diabetic control. In vitro studies also support the antioxidant as well as antiglycative potential of guava leaves.
Chemokine (C-C motif) receptor 7 (CCR7), a class A subtype G-Protein Coupled Receptor (GPCR), is involved in the migration, activation and survival of multiple cell types including dendritic cells, T cells, eosinophils, B cells, endothelial cells and different cancer cells. Together, CCR7 signaling system has been implicated in diverse biological processes such as lymph node homeostasis, T cell activation, immune tolerance, inflammatory response and cancer metastasis. CCL19 and CCL21, the two well-characterized CCR7 ligands, have been established to be differential in their signaling through CCR7 in multiple cell types. Although the differential ligand signaling through single receptor have been suggested for many receptors including GPCRs, there exists no resource or platform to analyse them globally. Here, first of its kind, we present the cell-type-specific differential signaling network of CCL19/CCL21-CCR7 system for effective visualization and differential analysis of chemokine/GPCR signaling.Database URL:
http:// www. netpath. org/ pathways? path_ id= NetPath_ 46.
Context: Antiglycative potential of Psidium guajava L. (Myrtaceae) leaves has been established. However, the molecular basis of its antiglycative potential remains unknown. Objective: The ethyl acetate fraction of P. guajava leaves (PGEt) was evaluated to determine the cardioprotective effect and its mechanism of action compared to quercetin. Materials and methods: After the induction of diabetes by streptozotocin (55 mg/kg body weight), PGEt and quercetin (50 mg/kg body weight) was administered for 60 days. Rats were grouped as follows: Group C: Control, Group D: Diabetic, Group D þ E: Diabetic rats treated with PGEt, Group D þ Q: Diabetic rats treated with quercetin. The antiglycative potential was evaluated by assaying glycosylated haemoglobin, serum fructosamine and advanced glycation end product levels. The differential receptor for advanced glycation end products and nuclear factor kappa B (NFjB) protein levels was determined by western blot and the transcript level changes of connective tissue growth factor (CTGF), brain natriuretic peptide (BNP) and TGF-b1 in heart tissue were assessed by RT-PCR analysis. Results: Glycated haemoglobin and serum fructosamine levels were found to be enhanced in diabetic rats when compared with control. Administration of PGEt significantly reduced the glycated haemoglobin and fructosamine levels to a larger extent than quercetin treated diabetic rats. PGEt reduced the translocation of NFjB from cytosol to nucleus when compared with diabetic rats. Expression of TGF-b1, CTGF and BNP was downregulated in PGEt treated groups compared with diabetic controls. Discussion and conclusion: Administration of PGEt ameliorated diabetes associated changes in the myocardium to a greater extent than quercetin.
ARTICLE HISTORY
Earlier studies from one of the investigator's laboratory have demonstrated the presence of a high molecular weight protein (182 kDa) in the blood serum of laboratory animals subjected to pressure-induced cardiac hypertrophy and suggested that this protein may be involved in the development of cardiac hypertrophy. Studies have shown that this protein is also involved in earlier stages of cardiac complications associated with diabetes, but the role of this protein in diabetic heart is less understood. So we aimed to check whether this protein is having any protective role in diabetic heart. The protein was purified from serum of rats induced with cardiac hypertrophy and the purified protein was injected through tail vein of diabetic rats for further studies. The results of various antioxidant enzymes and the TBARS levels have indicated the antioxidant activity of this protein. Real-time PCR analysis of gene expression revealed the upregulation of certain muscle-specific genes like β-MHC, MLC-2, and skeletal α actin in diabetic group and also in presence of 182-kDa protein. The results further showed a down regulation of genes such as cardiac α-actin and α- MHC implicating the role of this protein in the development of cardiac hypertrophy in diabetes. Increased cardiac hypertrophy as revealed by the expression of various genes and improved antioxidant potential in presence of 182 kDa protein in diabetes at the earlier stages is beneficial for counteracting the myocardial damage associated with diabetes.
Interleukin-11 (IL-11) is a pleiotropic cytokine that belongs to gp130 family. It plays a signifi cant role in the synthesis and maturation of hematopoietic cells, inhibition of adipogenesis, regulation of embryo implantation, and trophoblasts invasion. Although IL-11 signaling has been described in several biological processes, a centralized resource documenting these molecular reactions induced by IL-11 is not publicly available. In the current study, we have manually annotated the molecular reactions and interactions induced by IL-11 from literature available. We have documented 40 unique molecules involved in 18 protein -protein interactions, 26 enzyme -substrate reactions, 7 translocation events, and 4 activation/ inhibition reactions. We have also annotated 23 genes reported to be differentially regulated under IL-11 stimulation. We have enabled the data availability in standard exchange formats from ' NetPath ' , a repository for signaling pathways. We believe that this will help in the identifi cation of potential therapeutic targets in IL-11-associated disorders.
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