Diabetes has been considered as the most dreaded non-communicable disease consuming the mankind rapidly. WHO has predicted the number of diabetics to be approximately 366 millions by 2030. The disease is characterized by hyperglycemia and... more
Diabetes has been considered as the most dreaded non-communicable disease consuming the mankind rapidly. WHO has predicted the number of diabetics to be approximately 366 millions by 2030. The disease is characterized by hyperglycemia and the basic symptoms are polyphagia, polydipsia and polyuria. The autoimmune type 1 diabetes represent almost 1% of the total diabetic population, the rest being that of type 2 diabetes (T2D). Type 2 diabetes has been linked to a variety of factors such as heredity, environmental factors, unhealthy eating habits, sedentary lifestyle, stress etc. The uncontrolled hyperglycemia has profound dele- terious effects on almost all the organs and results in various cardiovascular disorders, retinopathy, neuropathy, and nephropathy. Recent studies have revealed an array of pul- monary dysfunctions related with T2D ranging from respiratory defects to tuberculosis. Diabetes also predisposes the person to hepatic dysfunctions like NAFLD and HCC and a range of infections at various sites which are difficult to manage. Post-surgical infections are of special interest for subjects with uncontrolled hyperglycemia prior to surgery. Scientists all over the world are revealing different pathways and associated therapies for type 2 diabetes in order to control the pathological effects covering almost whole body physiology.
World Health Organization (WHO) considers obesity as one of the fastest growing metabolic disorders other than diabetes. It is a complex interplay of lifestyle and associated genes. Obesity has been considered as a disease with multiple... more
World Health Organization (WHO) considers obesity as one of the fastest growing metabolic disorders other than diabetes. It is a complex interplay of lifestyle and associated genes. Obesity has been considered as a disease with multiple targets and very often compared in this sense with its sibling disease type 2 diabetes. The disease is pathology of the adipocytes and develops as a result of hypertrophy and hyperplasia of these cells, former being the major concern but its effects could be seen on various organs in the form of cardio-vascular disease, stroke, cancer, diabetes, sexual dysfunction, respiratory problems and many more. An increase in the lipid content of the adipocytes changes the physiology of these cells towards more inflammatory phenotype. The array of molecules or adipokines secreted by these cells varies in concentration and type among healthy and obese subjects. On one hand where adiponectin concentration decreases, the resistin concentration increases resulting in insulin resistance among many other adipokine related effects. Specifically, an obese person develops hyperlipidemia, insulin resistance, vascular blockage, sleep apnoea, cancer etc. This review is an attempt to focus, in detail, about obesity related complications.
Alzheimer's disease (AD) is a neurodegenerative disorder in which the death of brain cells causes memory loss and cognitive decline i.e. dementia. The disease starts with mild symptoms and gradually becomes severe. AD is one of the... more
Alzheimer's disease (AD) is a neurodegenerative disorder in which the death of brain cells causes memory loss and cognitive decline i.e. dementia. The disease starts with mild symptoms and gradually becomes severe. AD is one of the leading causes of mortality worldwide. Several different hallmarks of the disease have been reported such as deposits of β-amyloid around neurons, hyperphosphorylated tau protein, oxidative stress, dyshomeostasis of bio-metals, low levels of acetylcholine etc. AD is not simple to diagnose since there is no single diagnostic test for it. Pharmacotherapy for AD currently provides only symptomatic relief and mostly targets cognitive revival. Computational biology approaches have proved to be reliable tools for selection of novel targets and therapeutic ligands. Molecular docking is a key tool in computer-assisted drug design and development. Docking has been utilized to perform virtual screening on large libraries of compounds, and propose structural hypotheses of how the ligands bind with the target with lead optimization. Another potential application of docking is optimization stages of the drug-discovery cycle. This review summarizes the known drug targets of AD, in vivo active agents against AD, state-of-the-art docking studies done in AD and future prospects of the docking with particular emphasis on AD.
GSK-3 is a member of cellular kinases with diversified functions such as cellular differentiation, metabolic signaling, neuronal functions and apoptosis. It has been validated as an important therapeutic target in Alzheimer’s disease and... more
GSK-3 is a member of cellular kinases with diversified functions such as cellular differentiation, metabolic signaling, neuronal functions and apoptosis. It has been validated as an important therapeutic target in Alzheimer’s disease and type 2 diabetes. Few molecules targeting GSK-3 are currently in clinical trials. In this study, we have compared certain docking and computational ADME (Absorption, Distribution, Metabolism, Excretion) parameters of a few GSK-3 targeted ligands (Indirubin, Hymenialdisine, Meridianins, 6-bromoindirubin-3-oxime) against two control molecules (Tideglusib and LY-2090314) to derive and analyze the basic drug-like properties of the test compounds. Docking between the GSK-3 and various ligands was done using AutoDock while ADME parameters were derived from ADMET server PreADMET and admetSAR. Various docked images were retrieved from docking, indicating the docking sites in the target protein. Out of four compounds tested, 6-bromoindirubin-3-oxime (6-BIO) was found as the best docking and ADME parameters, followed by Hymenialdisine (HMD). The LigPlot interaction results show two residues Leu (188) and Thr (138) to be common at the interaction site. The LD50 of 6-BIO is better than one of the control ligands while very similar to the other. Some of the parameters were very similar to the control ligands, thus, making it a suitable candidate among the test ligands. From this in-silico study, we concluded that 6-BIO is a potent drug candidate which could be further tested in vitro and in vivo to establish a drug molecule. Since, 6-BIO is a chemically modified form of the basic molecule Indirubin, we can hypothesize that certain other modified indirubins could be tested as GSK-3 targeted ligands.
Amyloidogenic pathway in Alzheimer’s disease (AD) involves breakdown of APP by 𝛽-secretase followed by 𝛾-secretase and results in formation of amyloid beta plaque. 𝛽-secretase has been a promising target for developing novel... more
Amyloidogenic pathway in Alzheimer’s disease (AD) involves breakdown of APP by 𝛽-secretase followed by 𝛾-secretase and results in formation of amyloid beta plaque. 𝛽-secretase has been a promising target for developing novel anti-Alzheimer drugs. To test different molecules for this purpose, test ligands like acylguanidine 7a, rosiglitazone, pioglitazone, and tartaric acid were docked against our target protein 𝛽-secretase enzyme retrieved from Protein Data Bank, considering MK-8931 (phase III trial, Merck) as the positive control. Docking revealed that, with respect to their free binding energy, acylguanidine 7a has the lowest binding energy followed by MK-8931 and pioglitazone and binds significantly to 𝛽-secretase. In silico ADMET predictions revealed that except tartaric acid all other compounds had minimal toxic effects and had good absorption as well as solubility characteristics. These compounds may serve as potential lead compound for developing new anti-Alzheimer drug.
Non-parenteral drug delivery routes primarily remove the local pain at the injection site. The drugs administered through the oral route encounter the process of hepatic first pass metabolism. Among the alternative delivery routes,... more
Non-parenteral drug delivery routes primarily remove the local pain at the injection site. The drugs administered through the oral route encounter the process of hepatic first pass metabolism. Among the alternative delivery routes, mucosal route is being investigated as the most preferred route. Different mucosal routes include the gastrointestinal tract (oral), vagina, buccal cavity and nasal cavity. Novel formulations are being developed using natural and synthetic polymers that could increase the residence time of the drug at mucosal surface in order to facilitate permeation and reduce (or bypass) the first pass metabolism. For recombinant drugs, the formulations are accompanied by enzyme inhibitors and penetration enhancers. Buccal cavity (buccal and sublingual mucosa) has smaller surface area than the gastrointestinal tract but the drugs can easily escape the first pass metabolism. Chitosan is the most applied natural polymer while synthetic polymers include Carbopol and Eudragit. Chitosan has inherent properties of mucoadhesion and penetration enhancement apart from biodegradability and efflux pump inhibition. This review hoards the important research purview of chitosan as a compatible drug carrier macromolecule for mucosal delivery on single platform.
For various biomedical applications, biopolymeric films are often crosslinked using chemical crosslinker such as glutaraldehyde, which is considered as a toxic chemical. In this report, we have prepared and characterized biopolymeric... more
For various biomedical applications, biopolymeric films are often crosslinked using chemical crosslinker such as glutaraldehyde, which is considered as a toxic chemical. In this report, we have prepared and characterized biopolymeric films using different combinations of chitosan, CMC, alginate and PVA using glyoxal as the crosslinker. The prepared films were subjected to various physico-chemical and mechanical characterizations such as swelling index, surface pH, surface morphology analysis using SEM, interact ion study using XRD, flexibility study using tensile testing and hardness testing. Glyoxal crosslinking resulted in variation of physico-chemical and mechanical alteration of the chitosan-PVA films while it had the negligible effect on the CAP film. Further, the hardness of the films demonstrated a decrease in value in the crosslinked films as compared to non-crosslinked films. We have interpreted that glyoxal is a potential crosslinker for chitosan-based composite polymers while in this case, it did not show any significant effect on CMC and alginate based composite structures. Therefore, using this type of films would be the cheap, safe and new alternative in drug delivery and other biomedical applications.
A B S T R A C T World Health Organization (WHO) has identified diabetes as one of the fastest growing non-communicable diseases with 422 million patients around the world in 2014. Diabetes, a metabolic disease, is characterized primarily... more
A B S T R A C T World Health Organization (WHO) has identified diabetes as one of the fastest growing non-communicable diseases with 422 million patients around the world in 2014. Diabetes, a metabolic disease, is characterized primarily by hyperglycemia which results in various macrovascular and microvascular complications like cardiovascular disease and neuropathies which can significantly deteriorate the quality of life. The body either does not manufactures enough insulin (type 1 diabetes or T1DM) or becomes insensitive to physiologically secreted insulin or both (type 2 diabetes or T2DM). The majority of the diabetic population is affected by type 2 diabetes. Currently, hyperglycemia is treated by a broad range of molecules such as biguanides, sulfonylurea, insulin, thiazolidinediones, incretin mimetics, and DPP-4 inhibitors exerting different mechanisms. However, new drug classes have indeed come in the market such as SGLT-2 inhibitors and other are in the experimental stages such as GPR 40 agonists, GSK-3 inhibitors, GK activators and GPR21 inhibitors which definitely could be anticipated as safe and effective for diabetes therapy. This article reviews the general approach to currently approved therapies for type 2 diabetes and focusing on novel approaches that could be a panacea and might be useful in the future for diabetes patients.
Anaerobic bacteria isolated from industrial wastewater and soil samples were tested for current production in double chambered Microbial fuel cell (MFC), made from glass tubes (50 ml) and graphite rods as electrodes. The MFC developed... more
Anaerobic bacteria isolated from industrial wastewater and soil samples were tested for current production in double chambered Microbial fuel cell (MFC), made from glass tubes (50 ml) and graphite rods as electrodes. The MFC developed from these isolates was characterised by measuring the voltage, current, current density and power density across the cell. Of all the cultures, the isolate from Amleshwar industry water sample (WS 1) showed the maximum value for all the parameters tested i.e. voltage = 542mV, current = 0.272 mA, current density = 183.44 mA/m2 and power density = 99.42 mW/m2. Once the exoelectrogenic activity of the isolates was confirmed by current production, these were tested for hydrogen production in a single chambered Microbial electrolytic cell (MEC). The MECs were constructed using air-sealed plastic containers of working volume 200 ml with graphite rods as electrodes and an external voltage supply of 0.7 V. Three MECs were operated with different mixed culture...
Response surface methodology was used to optimise a two-step process of cellulase mediated saccharification of rice straw by an isolated bacterium Lysinibacillus sphaericus. CMC concentration, yeast extract, pH and incubation temperature... more
Response surface methodology was used to optimise a two-step process of cellulase mediated saccharification of rice straw by an isolated bacterium Lysinibacillus sphaericus. CMC concentration, yeast extract, pH and incubation temperature were optimised for cellulase production using a central composite design and their optimum values were determined to be 4.3% (w/v), 2.1% (w/v), 6.2 and 45.2 °C respectively. The CMCase activity at these values was 5.16±0.07 U/ml, which was 2.5 times that of the un-optimised system. Similarly, pretreated rice straw, enzyme load, incubation time and Tween-80 concentrations were optimised for enhanced saccharification of rice straw by optimised cellulase preparations, and their optimum values were calculated as 1.84% (w/v), 40 U, 57.4 h and 0.76 mM respectively. A percent saccharification of 69.5% was reported at optimal conditions. HPLC analysis revealed that hydrolysate produced at optimal conditions of saccharification constituted 70.8% of glucose.
