Mohd. Haris Siddiqui

Biophysical Evaluation of Radiofrequency Electromagnetic Field Effects on Male Reproductive Pattern

There are possible hazardous health effects of exposure to radiofrequency electromagnetic radiations emitted from mobile phone on the human reproductive pattern. It is more effective while keeping mobile phones in pocket or near testicular organs. Present review examines the possible concern on radio frequency radiation interaction and biological effects such as enzyme induction, and toxicological effects, including genotoxicity and carcinogenicity, testicular cancer, and reproductive outcomes. Testicular infertility or testicular cancer due to mobile phone or microwave radiations suggests an increased level of reactive oxygen species (ROS). Though generation of ROS in testis has been responsible for possible toxic effects on physiology of reproduction, the reviews of last few decades have well established that these radiations are very harmful and cause mutagenic changes in reproductive pattern and leads to infertility. The debate will be focused on bio-interaction mechanism between mobile phone and testicular cancer due to ROS formation. This causes the biological damage and leads to several changes like decreased sperm count, enzymatic and hormonal changes, DNA damage, and apoptosis formation. In the present review, physics of mobile phone including future research on various aspects has been discussed.

Titanium dioxide nanoparticles as guardian against environmental carcinogen benzo[alpha]pyrene.

Polycyclic aromatic hydrocarbons (PAH), like Benzo[alpha]Pyrene (BaP) are known to cause a number of toxic manifestations including lung cancer. As Titanium dioxide Nanoparticles (TiO2 NPs) have recently been shown to adsorb a number of PAHs from soil and water, we investigated whether TiO2 NPs could provide protection against the BaP induced toxicity in biological system. A549 cells when co-exposed with BaP (25 µM, 50 µM and 75 µM) along with 0.1 µg/ml,0.5 µg/ml and 1 µg/ml of TiO2 NPs, showed significant reduction in the toxic effects of BaP, as measured by Micronucleus Assay, MTT Assay and ROS Assay. In order to explore the mechanism of protection by TiO2 NP against BaP, we performed in silico studies. BaP and other PAHs are known to enter the cell via aromatic hydrocarbon receptor (AHR). TiO2 NP showed a much higher docking score with AHR (12074) as compared to the docking score of BaP with AHR (4600). This indicates a preferential binding of TiO2 NP with the AHR, in case if both the TiO2 NP and BaP are present. Further, we have done the docking of BaP with the TiO2 NP bound AHR-complex (score 4710), and observed that BaP showed strong adsorption on TiO2 NP itself, and not at its original binding site (at AHR). TiO2 NPs thereby prevent the entry of BaP in to the cell via AHR and hence protect cells against the deleterious effects induced by BaP.

Multiple Targets for the Management of Alzheimer’s Disease

AD is a progressive and irreversible neurodegenerative disease and the most common cause of dementia in the elderly population. Βeta- amyloid cascade formation along with several cytoskeleton abnormalities succeeding to the hyperphosphorylation of microtubule-associated tau protein in neurons leads to the elicitation of several neurotoxic incidents. As an outcome of these phenomena, steady growth of dementia in aged population is becoming ubiquitous in both developed and developing countries. Thus, the key aspiration is to endow with stable daily life functionality to the person suffering from dementia and to cut down or slower the symptoms of disease leading to disruptive behavior. In sight of this, the proteins amyloid-beta, BACE-1, RAGE and AChE are being aimed for the treatment of AD successfully. Currently, there are several medicines for the treatment of AD under survey like Galangin, Cymserine, Tolserine, Bisnorcymserine and Huperzine A. The article emphasizes clinical and neurobiological aspects of AD. The purpose of this review article is to provide a brief introduction of AD along with the related concept of beta-secretase, beta amyloid and neurotransmitter in the progression of disease. In the present review, we summarize the available evidence on the new therapeutic approaches that target amyloid and neurotransmitter in the AD.

Molecular interaction analysis of cigarette smoke carcinogens NNK and NNAL with enzymes involved in DNA repair pathways: An in silico approach.

DNA damage occurs almost all the times in cells, but is repaired also continuously. Occurrence of all these mutations and their accumulation in one cell which finally becomes tumorigenic/carcinogenic appears possible if the DNA repair mechanism is hampered. We hypothesize that alterations in DNA repair pathways, either all or at least at one i.e. genetic, translational or posttranslational level, becomes quite imperative for the initiation and progression of Cancer. Therefore, we investigated the interaction capability of some carcinogens with the enzymes involved in the DNA repair mechanisms. Cigarette smokes derivatives like NNK and NNAL are well established carcinogens. Hence, we analyzed 72 enzymes involved in the DNA repair Mechanisms for their interactions with ligands (NNK and NNAL). The binding efficiencies with enzymes ranging from +36.96 to -7.47 Kcal/Mol. Crystal Structure of Human Carbonmonoxy-Haemoglobin at 1.25 Å Resolution, PDB ID-1IRD as a +Ve control, showed binding energy -6.31 to -6.68 Kcal/Mol. and Human heat shock factor-binding protein 1, PDB ID- 3CI9 as a -Ve control, showed - 3.91 to +2.09 Kcal/Mol. Binding was characterized for the enzymes sharing equivalent or better interaction as compared to +Ve control. Study indicated the loss of functions of these enzymes, which probably could be a reason for fettering of DNA repair pathways resulting in damage accumulation and finally cancer formation.

Compounds isolated from Ageratum houstonianum inhibit the activity of matrix metalloproteinases (MMP-2 and MMP-9): An oncoinformatics study

Background: In osteosarcoma tissue, both MMP-2 and MMP-9 are over expressed compared to their expression in non-affected stromal tissue. Hence, gelatinases are attractive targets for anti-osteosarcoma drugs. Objective: To study the inhibitory activity of compounds isolated from Ageratum houstonianum against MMP-2 and MMP-9 by in-silico approach. Material and Methods: We performed docking study using ‘Autodock 4.2’ between 1,2-benzenedicarboxylic acid-bis (2-ethylhexyl) ester; squalene; 3,5-bis (1,1-dimethylethyl) phenol; pentamethyl tetrahydro-5H-chromene; (1, 4-cyclohexylphenyl) ethanone and 6-vinyl-7-methoxy-2,2-dimethylchromene with MMP-2 and MMP-9. Results: Among all six compounds isolated from Ageratum houstonianum, (1, 4-cyclohexylphenyl) ethanone showed the maximum potential as a putative inhibitor of both MMP-2 and MMP-9 enzymes with reference to ΔG (−7.95 and −8.2 kcal/mol, respectively) and Ki (1.48 and 0.98 μM, respectively) values. Total intermolecular energy of docking for (1, 4-cyclohexylphenyl) ethanone-MMP catalytic domain-interaction was found to be −8.55 kcal/mol for MMP-2 and −9.21 kcal/mol for MMP-9. Conclusion: This study explores molecular interactions between human MMPs (MMP-2 and MMP-9) and six natural compounds. This study predicts that (1,4-cyclohexylphenyl) ethanone is a more efficient inhibitor of human MMP-2 and MMP-9 enzymes compared to the other natural compounds used in this study with reference to Ki and ΔG values.

LPO and ROS Production in Rat Brain Exposed to Microwaves: Computational Elucidation of Melatonin in Repair System

It is widely accepted that non-ionizing electromagnetic fields are present in the environment and are alarming as a major pollutant or electro-pollutant for health risk. The present study aimed to investigate the protective measures of melatonin against exposure of microwave radiations. Study also explored the mechanistic correlation among microwave radiation, melatonin and biological effects by computational method. For this, 60-day-old male Wistar rats were divided into four groups (n = 4/group): sham exposed (control), Melatonin (Mel) treated (2 mg/kg), 2.45 GHz microwave (MWs) exposed and MWs + Mel treated. Exposure took place in Plexiglas cages for 2 h a day for 35 days where, power density (0.2 mW/cm2) and specific absorption rate (SAR-0.14 W/kg) were estimated. Results show that melatonin prevent oxidative damage biochemically by significant decrease (p < 001) the levels of lipid peroxide (LPO) and reactive oxygen species (ROS) in the brain. However, exposure of microwave individually shows significant changes in LPO and ROS level. The effective dose of melatonin was validated by in silico method and which reveals the interaction of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) Eenzmyes of Central Nervous System (CNS) with melatonin. Where, AChE showed better interaction with the binding energy of −9.01 kcal/mol and inhibition constant 3.11 uM by comparing with BuChE. These results concluded that the melatonin has strong antioxidative potential against microwave radiation, which could be achieved by an implementation of computational approach.

α-Amylase Inhibitor’s Performance in the Control of Diabetes Mellitus: An Application of Computational Biology

Diabetes mellitus is the most widespread disorders prevalent in current period. α-Amylase enzyme plays a key role in the onset of the abnormal condition by breaking starch into glucose; hence its inhibitors need to be studied thoroughly. Due to the various side effects posed by the existing commercial non-proteinaceous inhibitors, exploration of the natural plant-based inhibitors of the enzyme is the present-day demand. Ample of plants have been extensively studied and reported to exhibit hypoglycaemic properties. This article describes the mode of action of amylase enzyme, phytochemicals which behave as amylase inhibitors and classes of its inhibitors and summarizes various plants studied for their enzyme inhibitory properties including computational tools and techniques to analyse the binding pattern exploration of inhibitors using molecular interaction with enzymes of interest.

Herbal Remedies: A Boon for Diabetic Neuropathy

ABSTRACT Diabetic neuropathy is a chronic complication of diabetes mellitus affecting about 50% of patients. Its symptoms include decreased motility and severe pain in peripheral parts. The pathogenesis involved is an abnormality in blood vessels that supply the peripheral nerves, metabolic disorders such as myo-inositol depletion, and increased nonenzymatic glycation. Moreover, oxidative stress in neurons results in activation of multiple biochemical pathways, which results in the generation of free radicals. Apart from available marketed formulations, extensive research is being carried out on herbal-based natural products to control hyperglycemia and its associated complications. This review is focused to provide a summary on diabetic neuropathy covering its etiology, types, and existing work on herbal-based therapies, which include pure compounds isolated from plant materials, plant extracts, and Ayurvedic preparations.

Decoding the antineoplastic efficacy of Aplysin targeting Bcl-2: A de novo Perspective

The B-cell lymphoma-2 (Bcl-2) family proteins have been attributed to be the key regulators in programmed cell death and apoptosis with a prominent role in human cancer. Understanding the fundamental principles of cell survival and death have been the main cornerstone in cancer drug discovery for identification of novel anticancer agents. In this context the Bcl-2 family of anti-and pro-apoptotic proteins provide an excellent opportunity for development of anticancer agents, as blocking the Bcl-2 or Bcl-XL functionally promotes apoptosis in tumor cells and also sensitize them to chemo- and radiotherapies. The present study reports the identification of novel Aplysin analogs as BCL-2 inhibitors from a sequential virtual screening approach using drug-like, ADMET, docking, pharmacophore filters and molecular dynamics simulation. We identified promising Aplysin analogs that have a potential to be Bcl-2 inhibitors just like the standard drug Obatoclax. One of the compound analog 11 was identified to be a promising inhibitor of Bcl-2 in the docking, pharmacophore and simulation based models.The molecular modeling information provided here can be vital in designing of the novel Bcl-2 inhibitors.

Salinity–induced modulations in the protective defense system and programmed cell death in Nostoc muscorum

To study the biochemical adaptive responses of the blue green algae Nostoc muscorum to the salinity- induced stress they were exposed to various concentrations (5, 10, 15, 20 or 200 mM) of sodium chloride (NaCl). A dose-dependent inhibition of total protein content showed an adverse effect of NaCl on the growth of N. muscorum. Four-day treatment of NaCl (5–20 mM) progressively increased the content of the total peroxide with subsequent increase of the superoxide dismutase (SOD) activity, proline and total phenol content only up to 10 mM NaCl. Higher concentrations of NaCl caused significant decrease in both the enzymatic and non-enzymatic antioxidants. Induction of two polypeptides of ~29.10 and 40.15 kD as well as upregulation of many polypeptides as compared to control indicates the induction of SOD and dehydrin-like proteins, which supports the theory of adaptation against the salt stress. Furthermore, adaptation of N. muscorum to lower concentrations (5–20 mM) of NaCl was also confirmed by no fragmentation of DNA while DNA fragmentation indicating programmed cell death (PCD) could only be seen at 200 mM NaCl for 12 hours. We hypothesized that proline may confer a positive role to combat salinity stress and the same was confirmed by treatment of the test blue green algae with exogenous proline (1 and 10 μM). The results exhibited 16% reduction in the level of total peroxides, which is a well known oxidative stress marker in the 10 μM proline-treated NaCl group as compared to direct exposure to NaCl.