Mechanism and recent updates on insulin-related disorders.

Insulin, a small protein with 51 amino acids synthesized by pancreatic ß-cells, is crucial to sustain glucose homeostasis at biochemical and molecular levels. Numerous metabolic dysfunctions are related to insulin-mediated altered glucose homeostasis. One of the significant pathophysiological conditions linked to the insulin associated disorder is diabetes mellitus (DM) (type 1, type 2, and gestational). Insulin resistance (IR) is one of the major underlying causes of metabolic disorders despite its association with several physiological conditions. Metabolic syndrome (MS) is another pathophysiological condition that is associated with IR, hypertension, and obesity. Further, several other pathophysiological disorders/diseases are associated with the insulin malfunctioning, which include polycystic ovary syndrome, neuronal disorders, and cancer. Insulinomas are an uncommon type of pancreatic ß-cell-derived neuroendocrine tumor that makes up 2% of all pancreatic neoplasms. Literature revealed that different biochemical events, molecular signaling pathways, microRNAs, and microbiota act as connecting links between insulin disorder and associated pathophysiology such as DM, insuloma, neurological disorder, MS, and cancer. In this review, we focus on the insulin-related disorders and the underlying mechanisms associated with the pathophysiology.

Exploring the Role of Glycolytic Enzymes PFKFB3 and GAPDH in the Modulation of Aß and Neurodegeneration and Their Potential of Therapeutic Targets in Alzheimer's Disease.

Alzheimer's disease (AD) is presently the 6th major cause of mortality across the globe. However, it is expected to rise rapidly, following cancer and heart disease, as a leading cause of death among the elderly peoples. AD is largely characterized by metabolic changes linked to glucose metabolism and age-induced mitochondrial failure. Recent research suggests that the glycolytic pathway is required for a range of neuronal functions in the brain including synaptic transmission, energy production, and redox balance; however, alteration in glycolytic pathways may play a significant role in the development of AD. Moreover, it is hypothesized that targeting the key enzymes involved in glucose metabolism may help to prevent or reduce the risk of neurodegenerative disorders. One of the major pro-glycolytic enzyme is 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-3 (PFKFB3); it is normally absent in neurons but abundant in astrocytes. Similarly, another key of glycolysis is glyceraldehyde-3-phosphate dehydrogenase (GAPDH) which catalyzes the conversion of aldolase and glyceraldehyde 3 phosphates to 1,3 bisphosphoglycerate. GAPDH has been reported to interact with various neurodegenerative disease-associated proteins, including the amyloid-ß protein precursor (AßPP). These findings indicate PFKFB3 and GAPDH as a promising therapeutic target to AD. Current review highlight the contributions of PFKFB3 and GAPDH in the modulation of Aßand AD pathogenesis and further explore the potential of PFKFB3 and GAPDH as therapeutic targets in AD.

Proteomic and molecular evidences of Il1rl2, Ric8a, Krt18 and Hsp90b1 modulation during experimental hepatic fibrosis and pomegranate supplementation.

The inspection of variations in the proteomic aspects conspire the biomarker discovery in diagnostics of peculiar diseases. Recent developments in high-throughput proteomic techniques have provided leverage in the discovery of biomarkers during the etiology of various diseases. We identified potential biomarkers by utilizing proteomics, bioinformatics and gene expression studies. Meticulous assessment of collagen and hydroxyproline levels along with the glycogen and protein carbonyl levels exhibited deterioration in the N' - Nitrosodiethylamine (NDEA) administered rat livers and subsequent salubrious effect of pomegranate juice. The immunohistochemical inspection of iNOS and nitrite estimation indicated the peccant fibrotic alterations. 2D proteome profiling and MALDI-TOF MS/MS furthered the significant biomarkers to be analyzed for the gene ontology by PANTHER, cluster analysis by DAVID and network simulation by STRING 10.0. Several genes found relevant after MALDI analysis were evaluated by real-time PCR (RTPCR). Our data revealed CYP2b15, HSP70, TRFE, HPT, Il1rl2, Ric8a, Krt18, Hsp90b1 and iNOS as novel biomarkers for the mechanism of pomegranate against liver fibrosis. It can be inferred that NDEA-induced liver fibrosis actuates various biological pathways by the identified biomarkers and pomegranate juice modifies them.

Pomegranate action in curbing the incidence of liver injury triggered by Diethylnitrosamine by declining oxidative stress via Nrf2 and NFκB regulation.

Unearthing and employment of healthy substitutes is now in demand to tackle a number of diseases due to the excessive repercussions of synthetic drugs. In this frame of reference pomegranate juice (PGJ) is a boon comprising of anthocyanins and hydrolysable tannins, known for its anti-oxidant and anti-inflammatory properties. Despite various documented roles of PGJ, there are no studies on antifibrotic potential in NDEA-induced mammalian liver fibrotic model. Hepatic fibrosis in rats was induced by the intra-peritoneal injection of NDEA (10 mlkg-1b.wt. of 1% NDEA) in two weeks. Biochemical, histopathological and ultra-structural studies were carried out on control, fibrotic and treated rats. The liver function indices and LPO were increased significantly by intoxication of NDEA. The antioxidant status was disturbed with the decrease in SOD, GST and catalase in the liver and membrane-ATPases as well. Histopathological observations by H&E, M&T, picro-sirius and ultra-structural scrutiny by SEM and TEM indicated liver damage and increase in COX2 and α-SMA by NDEA which was successfully rectified by the supplementation of PGJ. PGJ abrogates liver fibrosis instigated by NDEA in Wistar rats by declining oxidative stress via regulation of Nrf2 and NFκB. These findings point towards pomegranate as a potential and efficacious therapeutic agent against liver fibrosis.

Proteomic-genomic adjustments and their confluence for elucidation of pathways and networks during liver fibrosis.

Proteomics is the study of the functional aspect of all expressed proteins. Laudable progress has been made in context to protein profiles and interactions and this progress has been augmented with the help of the blueprint provided by the genomics field. Liver fibrosis is the starting point of various chronic liver diseases ultimately leading to cirrhosis. Current advances in high-throughput proteomic technologies have manifested the potential to reveal biomarkers for the diagnosis of liver fibrosis. This review explores the key up-to-date breakthroughs in proteo-genomics and their implementation to the important clinical question of liver fibrosis. The combination of proteomics with the informatics field, discovery of biomarkers, delineation of clinical pathways, challenges in proteomics for future research in relevance to clinical hepatology have been critically discussed.