miRNA in Parkinson's disease: From pathogenesis to theranostic approaches

Parkinson's disease (PD) is an age associated neurological disorder which is specified by cardinal motor symptoms such as tremor, stiffness, bradykinesia, postural instability, and non-motor symptoms. Dopaminergic neurons degradation in substantia nigra region and aggregation of αSyn are the classic signs of molecular defects noticed in PD pathogenesis. The discovery of microRNAs (miRNA) predicted to have a pivotal part in various processes regarding regularizing the cellular functions. Studies on dysregulation of miRNA in PD pathogenesis has recently gained the concern where our review unravels the role of miRNA expression in PD and its necessity in clinical validation for therapeutic development in PD. Here, we discussed how miRNA associated with ageing process in PD through molecular mechanistic approach of miRNAs on sirtuins, tumor necrosis factor-alpha and interleukin-6, dopamine loss, oxidative stress and autophagic dysregulation. Further we have also conferred the expression of miRNAs affected by SNCA gene expression, neuronal differentiation and its therapeutic potential with PD. In conclusion, we suggest more rigorous studies should be conducted on understanding the mechanisms and functions of miRNA in PD which will eventually lead to discovery of novel and promising therapeutics for PD.     

Screening for microbial trehalases: extracellular trehalases produced byFusarium species

Two hundred microorganisms comprising actinomycetes, bacteria, fungi and yeasts were screened for extracellular trehalases by their growth on trehalose in solid and liquid culture.Candida albicans, Gelasinospora retispora and four isolates belonging to the genusFusarium produced extracellular trehalases. The production of trehalase by theFusarium spp. was influenced by the nutrient composition of the medium and the carbon source; of the substrates examined starch produced the highest enzyme titre. Trehalase was an inducible enzyme and was repressed when theFusarium spp. were grown on glucose. The properties of the trehalases from two of theFusarium spp. (isolates MU-105 and TR-8) were typical of non-regulatory trehalases. Activity of several α-glucosidases, an amylase, an invertase and a cellobiase was also demonstrated when the two isolates were grown on trehalose.     

Lacrimal Proline Rich 4 (LPRR4) Protein in the Tear Fluid Is a Potential Biomarker of Dry Eye Syndrome

Dry eye syndrome (DES) is a complex, multifactorial, immune-associated disorder of the tear and ocular surface. DES with a high prevalence world over needs identification of potential biomarkers so as to understand not only the disease mechanism but also to identify drug targets. In this study we looked for differentially expressed proteins in tear samples of DES to arrive at characteristic biomarkers. As part of a prospective case-control study, tear specimen were collected using Schirmer strips from 129 dry eye cases and 73 age matched controls. 2D electrophoresis (2DE) and Differential gel electrophoresis (DIGE) was done to identify differentially expressed proteins. One of the differentially expressed protein in DES is lacrimal proline rich 4 protein (LPRR4). LPRR4 protein expression was quantified by enzyme immune sorbent assay (ELISA). LPRR4 was down regulated significantly in all types of dry eye cases, correlating with the disease severity as measured by clinical investigations. Further characterization of the protein is required to assess its therapeutic potential in DES.     

Sequence analysis,structure and binding site prediction of Sigma 1 receptor protein by in silico method

Sigma 1 Receptor is a subtype of opioid receptor that participates in membrane remodeling and cellular differentiation in the nervous system. Sigma1 Receptor protein with amino acid length ranging from 229 is widely distributed in the liver and moderately in the intestine, kidney, white pulp of the spleen, adrenal gland, brain, placenta and the lung. In this study, the three dimensional structure for sigma 1 receptor protein has been developed by in- silico analysis based on evolutionary trace analysis of 37 sigma proteins from different sources. The present work focus on identification of functionally important residues and its interaction with antipsychotic drugs reported in literature.     

Amino acids influence the glucose uptake through GLUT4 in CHO-K1 cells under high glucose conditions

According to studies earlier, amino acids have proven to be antidiabetic, antiglycating, and anticataractogenic. The present study was to explore whether amino acids as mixtures could enhance glucose uptake in CHO-K1 cells specifically. The cells in F-12K1 serum-free medium were exposed to normal (7 mM) and high glucose (12, 17 and 27 mM) in the presence and absence of amino acids mixture (AAM) in varying concentration (2.5, 5 and 10 mM). The mixture 5 and 10 mM AAM increased the 2-deoxyglucose (2DG) uptake at all glucose concentration significantly. There was also a significant increase in the GLUT4 (glucose transporter) translocation as revealed by flow cytometer. Addition of a mixture of amino acids was found to improve cell viability, which got altered by high glucose in the CHO-K1 cells. Amino acids as mixture had a beneficial effect in improving the net utilization of glucose as an additive effect with insulin.     

Comparative modeling of PON2 and analysis of its substrate binding interactions using computational methods

Paraoxonase (PON) constitutes a family of calcium-dependent mammalian enzymes comprising of PON1, PON2, and PON3. PON family shares ~60% sequence homology. These enzymes exhibit multiple activities like paraoxonase, arylesterase, and lactonase in a substrate dependent manner. Decreased PON activity has been reported in diseases like cardiovascular disease, atherosclerosis, and diabetes. Even though, PON2 is the oldest member of the family, PON1 is the only member studied in silico. In this study, the structure of PON2 was modeled using MODELLER 9v7 and its interactions with relevant ligands and it's physiological substrate homocysteine thiolactone was performed using AutoDock 4.0. The results reveal that PON1 and PON2 share common ligand binding patterns for arylesterase and lactonase activity, whereas in case of paraoxon binding, the residues involved in the interactions were different. Interestingly, the substrate HCTL was found to have the lowest free energy of binding (ΔG) and highest affinity for PON2 than PON1.     

Selective and frequency dependent predation of aquatic mosquito predator Diplonychus indicus Venkatesan & Rao (Hemiptera: Belostomatidae) on immature stages of three mosquito species

Frequency dependent mosquito larval size (II and IV instars) and species selection by the water bug Diplonychus indicus against three mosquito species Culex quinquefasciatus, Aedes aegypti and Anopheles stephensi was studied in the laboratory. The different frequencies used for each species selection were 20:30:50, 30:50:20, 50:20:30, 25:35:40, 35:40:25 and 40:25:35 of fourth instars of the respective three prey species. All nymphal water bugs (I–V instars) selected IV instar mosquito larvae and the mean proportion of late (larger) larvae eaten by the predator instars was significantly higher than the mean proportion of early (smaller) larvae eaten (F= 2.28; P < 0.001). In all six ratios used to determine the frequency dependent mosquito species selection, all the stages of the water bug selected Ae. aegypti over the other two species (F= 452.43; P < 0.001). The mean number of mosquito larvae eaten increased as its density increased based on various ratios of larvae offered. The study indicated that the predatory efficiency of D. indicus was high when Ae. aegypti was offered as prey, suggesting the utility of this mosquito predator in the control of dengue vectors.     

Plasma peptidome profiling of acute hepatitis E patients by MALDI-TOF/TOF

Background  

Hepatitis E is endemic to resource-poor regions, where it manifests as sporadic cases and large waterborne outbreaks. The disease severity ranges from acute self-limited hepatitis with low mortality to fulminant hepatic failure with high mortality. It is believed that the host response plays an important role in determining the progression and outcome of this disease. We profiled the plasma peptidome from hepatitis E patients to discover suitable biomarkers and understand disease pathogenesis.     

Hyperinsulinemia-induced vascular smooth muscle cell (VSMC) migration and proliferation is mediated by converging mechanisms of mitochondrial dysfunction and oxidative stress

Atherosclerosis is one of the major complications of diabetes and involves endothelial dysfunction, matrix alteration, and most importantly migration and proliferation of vascular smooth muscle cells (VSMCs). Although hyperglycemia and hyperinsulinemia are known to contribute to atherosclerosis, little is known about the specific cellular signaling pathways that mediate the detrimental hyperinsulinemic effects in VSMCs. Therefore, we investigated the cellular mechanisms of hyperinsulinemia-induced migration and proliferation of VSMCs. VSMCs were treated with insulin (100 nM) for 6 days and subjected to various physiological and molecular investigations. VSMCs subjected to hyperinsulinemia exhibited increased migration and proliferation, and this is paralleled by oxidative stress [increased NADPH oxidase activity, NADPH oxidase 1 mRNA expression, and reactive oxygen species (ROS) generation], alterations in mitochondrial physiology (membrane depolarization, decreased mitochondrial mass, and increased mitochondrial ROS), changes in mitochondrial biogenesis-related genes (mitofusin 1, mitofusin 2, dynamin-related protein 1, peroxisome proliferator-activated receptor gamma coactivator 1-alpha, peroxisome proliferator-activated receptor gamma coactivator 1-beta, nuclear respiratory factor 1, and uncoupling protein 2), and increased Akt phosphorylation. Diphenyleneiodonium, a known NADPH oxidase inhibitor significantly inhibited migration and proliferation of VSMCs and normalized all the above physiological and molecular perturbations. This study suggests a plausible crosstalk between mitochondrial dysfunction and oxidative stress under hyperinsulinemia and emphasizes counteracting mitochondrial dysfunction and oxidative stress as a novel therapeutic strategy for atherosclerosis.