A possible therapeutic potential of quercetin through inhibition of μ-calpain in hypoxia induced neuronal injury:a molecular dynamics simulation study

The neuroprotective property of quercetin is well reported against hypoxia and ischemia in past studies.This property of quercetin lies in its antioxidant property with blood-brain barrier permeability and anti-inflammatory capabilities.μ-Calpain,a calcium ion activated intracellular cysteine protease causes serious cellular insult,leading to cell death in various pathological conditions including hypoxia and ischemic stroke.Hence,it may be considered as a potential drug target for the treatment of hypoxia induced neuronal injury.As the inhibitory property of μ-calpain is yet to be explored in details,hence,in the present study,we investigated the interaction of quercetin with μ-calpain through a molecular dynamics simulation study as a tool through clarifying the molecular mechanism of such inhibition and determining the probable sites and modes of quercetin interaction with the μ-calpain catalytic domain.In addition,we also investigated the structure-activity relationship of quercetin with μ-calpain.Affinity binding of quercetin with μ-calpain had a value of –28.73 k J/mol and a Ki value of 35.87 μM that may be a probable reason to lead to altered functioning of μ-calpain.Hence,quercetin was found to be an inhibitor of μ-calpain which might have a possible therapeutic role in hypoxic injury.

Effect of protease inhibitor from Agaricus bisporus on glucose uptake and oxidative stress in 3T3-L1 adipocytes

Objective:To explore the effect of the protease inhibitor from Agaricus bisporus(J.E.Lange)Imbach(AbPI)on glucose uptake and oxidative stress in 3 T3-L1 adipocytes.Methods:Adipocytes were differentiated and stained with OilRed-O staining to confirm adipogenesis.The toxic/protective effect of AbPI on the adipocytes was determined by MTT assay,intracellular reactive oxygen species generation through flow cytometry,and morphologically through confocal microscopy using propidium iodide,4,6-diamino-2-phenylindol dihydrochloride,and 2’,7’-dichlorofluorescein diacetate dyes.The uptake of fluorescent glucose analog,2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-d-glucose by adipocytes was also studied through confocal microscopy.Results:MTT assay showed that the cell survival rate was(28.00±3.00)%,(92.33±2.60)%,and(71.34±2.10)%in the presence of 2 mM H2O2,AbPI alone,and AbPI and H2O2 both,respectively,in comparison to the control.Oil-Red-O staining indicated that Ab PI enhanced adipogenesis.AbPI stimulated the glucose uptake by adipocytes similar to the drug rosiglitazone,and showed insulinsensitizing effect in the presence of insulin,but failed to stimulate the uptake in the absence of insulin.Intracellular reactive oxygen species generation was reduced in differentiating adipocytes upon Ab PI treatment.Confocal microscopy showed that the damaged cell population rose to 3.50%,117.84%,and 261.50%in the presence of Ab PI alone,AbPI with H2O2,and H2O2 alone,respectively.Conclusions:The protease inhibitor enhances glucose uptake by adipocytes and exhibits a cytoprotective effect on them.

Synthesis of Single-stranded Polynorbornene with Pendant Group Bearing Benzenedicarboxaldehyde and Long Alkyl Chain

An unprecedented single-stranded polynorbornene with the pendant group containing benzenedicarboxaldehyde and a long alkyl chain（12） was synthesized by ring-open metathesis polymerization（ROMP） of the corresponding monomer（11）,which was obtained via the esterification of two crucial intermediates,namely,2-hexadecyloxy-5-hydroxymethyl-1,3-benzenedicarboxaldehyde（7,obtained via 6 steps） and 4-（4-aza-tricyclo[5.2.1.0 2.6 ]-dec-8en-4-yl）benzoic acid（10）.The target compound and all the intermediates were characterized by infrared（IR）,1 H NMR and high resolution mass spectroscopy（HRMS） analysis.

The Effect of Glandless Cottonseed Meal Content and Process Parameters on the Functional Properties of Snacks during Extrusion Cooking

The results of the present study indicate that glandless cottonseed meal (CSM) can be incorporated in extruded corn flour snacks at a 10% content level, which increases snack protein content to 12.8% and reduce fat content to 6.2%. To improve snacks’ nutritional quality, CSM and corn flour were extruded using a simple screw extruder. An expansion index (EI) ranging of 1.2 - 4.7 was obtained. Penetration force (PF) was 7 - 9 times harder than other extruded products. High extrusion temperature and high CSM concentrations decreased (p p p< 0.05) extrudates’ water solubility index. Extrusion conditions used showed a 68.5% starch gelatinization, and a starch availability of more than 97%, which explains the high expansion index obtained.

Artificial Neural Network Modeling to Predict the Non-Linearity in Reaction Conditions of Cholesterol Oxidase from <i>Streptomyces olivaceus</i><i>MTCC</i>6820

Cholesterol oxidase (COX) is widely used enzyme for total cholesterol estimation in human serum and for the fabrication of electro-chemical biosensors. COX is also used for the bioconversion of cholesterol;for the production of precursors of steroidal drugs and hormones. Enzyme activity depends decisively on defined conditions with respect to pH, temperature, ionic strength of the buffer, substrate concentration, enzyme concentration, reaction time. Standardization of these parameters is desirable to attain optimum activity of the enzyme. The present work aims to build a neural network model using five input parameters (pH, cholesterol concentration, 4-aminoantipyrine concentration, crude COX volume and horseradish peroxidase) and one output i.e., COX activity (U/ml) as a response. A feed forward back propagation neural network with Levenberg-Marquardt training algorithm was used to train the network. The network performance was assessed in terms of regression (R2), Mean Squared Error (MSE) and Mean Absolute Percentage Error (MAPE). A network topology of 5-10-1 was found to be optimum. The MSE, MAPE and R2 values of the neural model were 0.0075%, 0.12% and 0.9792% respectively. The maximum predicted activity of COX was 1.073 U/ml, which was close to the experimental value i.e., 1.1 U/ml at simulated optimum assay conditions. MSE and MAPE depicted the precision in the prediction efficiency of the developed ANN model. Higher R2 value showed a good correlation between the experimental and ANN predicted values. This proved the robustness of the ANN model to predict similar type of system (COX from other Streptomyces sp.) within the limits of the trained data set. The COX activity was enhanced by 1.71 folds after optimization of the reaction conditions.

Molecular Docking Studies of Myricetin and Its Analogues against Human PDK-1 Kinase as Candidate Drugs for Cancer

Phosphoinositide-dependent protein kinase-1 (PDK1), the class of serine threonine kinase, is a master regulator of the AGC family of kinases. It is a main component of the PI3K pathway. As it is reported that this pathway is most commonly, and this pathway is the most commonly deregulated among many cancers. So designing a selective inhibitor of PDK1 may have the efficacy as an anticancer agent. Herein, we describe our work focused on the structure based on screening of 95% similar analogues of Myricetin deposited in PubChem database as earlier studies have been suggested that myricetin acts as an anti cancer agent. Further molecular docking as well as the in silico ADMET studies are incorporated on these compounds to evaluate the binding and pharmacokinetic properties of these compounds. Due to low oral bioavailability, clinical use of myricetin is limited. Therefore this study is an attempt towards screening of structurally similar better compounds as compare with myricetin which can act as better inhibitor against PDK-1.

Resveratrol inhibits matrix metalloproteinases to attenuate neuronal damage in cerebral ischemia:a molecular docking study exploring possible neuroprotection

The main pathophysiology of cerebral ischemia is the structural alteration in the neurovascular unit, coinciding with neurovascular matrix degradation. Resveratrol has been reported to be one of the most potent chemopreventive agents that can inhibit cellular processes associated with ischemic stroke. Matrix metalloproteinases （MMPs） has been considered as a potential drug target for the treatment of cerebral ischemia. To explore this, we tried to investigate the inter-action of resveratrol with MMPs through molecular docking studies. At 30 minutes before and 2 hours after cerebral ischemia/reperfusion induced by occlusion of the middle cerebral artery, 40 mg/kg resveratrol was intraperitoneally administered. After resveratrol administration, neu-rological function and brain edema were significantly alleviated, cerebral infarct volume was signiifcantly reduced, and nitrite and malondialdehyde levels in the cortical and striatal regions were signiifcantly decreased. The molecular docking study of resveratrol and MMPs revealed that resveratrol occupied the active site of MMP-2 and MMP-9. The binding energy of the complexes was –37.848672 kJ/mol and –36.6345 kJ/mol for MMP-2 and MMP-9, respectively. In case of MMP-2, Leu 164, Ala 165 and Thr 227 were engaged in H-Bonding with resveratrol and in case of MMP-9, H-bonding was found with Glu 402, Ala 417 and Arg 424 residues. These ifndings collectively reveal that resveratrol exhibits neuroprotective effects on cerebral ischemia through inhibiting MMP-2 and MMP-9 activity.

Invitro Biodegradability of Silk Fibroin/Xanthan Biopolymeric Composite Scaffolds

Silk fibroin/xanthan scaffolds were prepared by blending silk fibroin and xanthan in the ratios 80SF:20Xa(SFX82),60SF:40Xa(SFX64),and 50SF:50Xa(SFX55)using freeze drying method.In-vitro degradation behavior of the prepared scaffolds was studied for 37 days in phosphate buffer saline.The degradation rate was the function of silk fibroin,xanthan and^-crystallite contents in the silk fibroin/xanthan composites.SFX82 degraded extremely slowly whereas SFX55 showed faster degradation rate.Hydrophilic xanthan was the main contributor of weight loss.SFX82 and SFX64 exhibited surface degradation whereas SFX55 showed bulk degradation which indicated that higher silk fibroin ratios favor surface degradation.Due to bulk degradation,SFX55 showed maximum surface roughness among the composite scaffolds.The FTIR spectrum revealed total loss of xanthan from the composites after degradation.The broad and low-intensity peaks in the FTIR spectrum of composite scaffolds con finned reduction in 0-sheet crystallite content during degradation.XRD analysis also confirmed reduction in 0-sheet crystals and revealed that degraded composite scaffold had predominantly amorphous structure.The degraded scaffold showed higher porous structure than the non-degraded scaffold.The in vitro degradability testing gives a good approximation of degradation of scaffold in vivo and helps in designing a robust biopolymeric composite scaffold for tissue engineering.

Synthesis of polynorbornene with pendant moiety bearing azide and terminal alkyne groups

A powerful approach to the synthesis of an unprecedented polynorbornene with pendant moiety bearing azide and terminal alkyne groups is developed. Two key intermediates, namely, 3-azido-5-（2-（trimethylsilyl）ethynyl） benzyl alcohol and 4-（4-azatricyclo [5.2.1.0^2.6]dec-8-en-4-yl） benzoic acid, were optimally synthesized for convergent synthesis of the corresponding monomer.

Trends in lactose-derived bioactives:synthesis and purification

Lactose obtained from cheese whey is a low value commodity despite its great potential as raw material for the production of bioactive compounds.Among them,prebiotics stand out as valuable ingredients to be added to food matrices to build up functional foods,which currently represent the most active sector within the food industry.Functional foods market has been growing steadily in the recent decades along with the increasing awareness of the World population about healthy nutrition,and this is having a strong impact on lactose-derived bioactives.Most of them are produced by enzyme biocatalysis because of molecular precision and environmental sustainability considerations.The current status and outlook of the production of lactose-derived bioactive compounds is presented with special emphasis on downstream operations which are critical because of the rather modest lactose conversion and product yields that are attainable.Even though some of these products have already an established market,there are still several challenges referring to the need of developing better catalysts and more cost-effective downstream operations for delivering high quality products at affordable prices.This technological push is expected to broaden the spectrum of lactose-derived bioactive compounds to be produced at industrial scale in the near future.