Shams Tabrez

Nanotechnology-based approaches in anticancer research

Cancer is a highly complex disease to understand, because it entails multiple cellular physiological systems. The most common cancer treatments are restricted to chemotherapy, radiation and surgery. Moreover, the early recognition and treatment of cancer remains a technological bottleneck. There is an urgent need to develop new and innovative technologies that could help to delineate tumor margins, identify residual tumor cells and micrometastases, and determine whether a tumor has been completely removed or not. Nanotechnology has witnessed significant progress in the past few decades, and its effect is widespread nowadays in every field. Nanoparticles can be modified in numerous ways to prolong circulation, enhance drug localization, increase drug efficacy, and potentially decrease chances of multidrug resistance by the use of nanotechnology. Recently, research in the field of cancer nanotechnology has made remarkable advances. The present review summarizes the application of various nanotechnology-based approaches towards the diagnostics and therapeutics of cancer.

Toxicological effects of major environmental pollutants: an overview

The last quarter of the twentieth century had witnessed a global surge in awakening against the unabated menace of environmental pollution. Among the various types of environmental pollution, water pollution is an age-old problem but it has gained an alarming dimension lately because of the problems of population increase, sewage disposal, industrial waste, radioactive waste, etc. Present scenario of water pollution calls for immediate attention towards the remediation and detoxification of these hazardous agents in order to have a healthy living environment. The present communication will deal with the toxicological effects of major environmental pollutants, viz. heavy metals, pesticides, and phenols.

Use of Pseudomonas spp. for the bioremediation of environmental pollutants: a review

Environmental pollution implies any alteration in the surroundings but it is restricted in use especially to mean any deterioration in the physical, chemical, and biological quality of the environment. All types of pollution, directly or indirectly, affect human health. Present scenario of pollution calls for immediate attention towards the remediation and detoxification of these hazardous agents in order to have a healthy living environment. The present communication will deal with the use of naturally occurring microbes capable of bioremediating the major environmental pollutants.

Effect of wastewater intake on antioxidant and marker enzymes of tissue damage in rat tissues: implications for the use of biochemical markers.

In the present study, alteration in antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), glutathione-S-transferase (GST) and glutathione peroxidase (GPx) and marker enzymes of tissue damage alanine transaminase (ALT), aspartate transaminase (AST) and alkaline phosphatase (ALP) with laboratory exposure to wastewaters from Aligarh (AWW) and Saharanpur (SWW) were investigated in rat liver and kidney. Levels of malondialdehyde (MDA), reduced glutathione (GSH) and hydrogen peroxide (H(2)O(2)) were also determined. A profound enhancement of 5 and 2.5-folds in MDA level was recorded in the liver and kidney respectively as a result of oral administration of SWW to the rats. Exposure to both AWW and SWW resulted in 3-4-fold increase in GR activity and 3-fold increase in SOD and ALT activity in the hepatic tissue compared to control values. Ingestion of AWW and SWW resulted in 3.5-fold rise in renal AST levels whereas AWW caused 75% decline in GST activity in kidney of treated rats. Results indicate that wastewater (AWW/SWW) caused severe damage to renal and hepatic tissues and the effect seems in part to be mediated by suppression of antioxidant system with GR and SOD as potential candidates for hepatic toxicity biomarkers of wastewaters.

A Synopsis on the Role of Tyrosine Hydroxylase in Parkinson's Disease

Parkinsons disease (PD) is a common chronic progressive neurodegenerative disorder in elderly people. A consistent neurochemical abnormality in PD is degeneration of dopaminergic neurons in substantia nigra pars compacta, leading to a reduction of striatal dopamine (DA) levels. As tyrosine hydroxylase (TH) catalyses the formation of L-dihydroxyphenylalanine (L-DOPA), the rate-limiting step in the biosynthesis of DA, the disease can be considered as a TH-deficiency syndrome of the striatum. Problems related to PD usually build up when vesicular storage of DA is altered by the presence of either α-synuclein protofibrils or oxidative stress. Phosphorylation of three physiologically-regulated specific sites of N-terminal domain of TH is vital in regulating its kinetic and protein interaction. The concept of physiological significance of TH isoforms is another interesting aspect to be explored further for a comprehensive understanding of its role in PD. Thus, a logical and efficient strategy for PD treatment is based on correcting or bypassing the enzyme deficiency by the treatment with L-DOPA, DA agonists, inhibitors of DA metabolism or brain grafts with cells expressing a high level of TH. Neurotrophic factors are also attracting the attention of neuroscientists because they provide the essential neuroprotective and neurorestorative properties to the nigrostriatal DA system. PPAR-γ, a key regulator of immune responses, is likewise a promising target for the treatment of PD, which can be achieved by the use of agonists with the potential to impact the expression of pro- and anti-inflammatory cytokines at the transcriptional level in immune cells via expression of TH. Herein, we review the primary biochemical and pathological features of PD, and describe both classical and developing approaches aimed to ameliorate disease symptoms and its progression.

Immunogenicity of DNA-advanced glycation end product fashioned through glyoxal and arginine in the presence of Fe3+: Its potential role in prompt recognition of diabetes mellitus auto-antibodies

Glyoxal, methylglyoxal and 3-deoxyglucosones are reactive dicarbonyl compounds, which transform free amino groups of proteins and lipoproteins macromolecule into advanced glycation end-products (AGEs). AGEs play a significant role in the pathophysiology of aging and diabetic complications because of their genotoxic effect. Glyoxal also reacts with free amino group of nucleic acids resulting in the formation of DNA-AGEs. The present study reports the genotoxicity and immunogenicity of AGEs formed by Glyoxal-Arginine-Fe(3+) (G-Arg-Fe(3+)) system as a glycating agent. Immunogenicity of native and G-Arg-Fe(3+)-DNA was probed in female rabbits. Immunofluorescence suggests the presence of immune complex deposition in the kidney section of immunized rabbits. Spectroscopic analysis and melting temperature indicates the structural modification in the human DNA. The modified human DNA is found to be highly immunogenic, whereas unmodified form was simply non-immunogenic. This study shows the presence of auto-antibodies against G-Arg-Fe(3+) modified human DNA in the sera of diabetes type 1 and in few cases type 2 patients due to secondary complications of nephropathy. The glyco-oxidative lesions have also been detected in the lymphocyte DNA isolated from patients having type 1 and type 2 diabetes. The results show structural perturbations generating new epitopes in G-Arg-Fe(3+)-DNA rendering it pretty immunogenic.

Current updates on computer aided protein modeling and designing

Determination of the three dimensional (3D) structure of a protein can provide important details about its biological functions and mechanism of action. However, despite their significance, the precise three-dimensional structures of most of the proteins are not fully determined till date. The main focus of the current review article is to gain a better understanding of the structural features of the proteins using computational techniques, and their relationship with function. Protein modeling and design is the method aimed to fold a primary amino acids sequence into protein structure with the ultimate goal of designing novel function and behavior. Moreover, proteins can also be designed from scratch or by similarity with the known protein structure. In the current article we have tried to cover various computer aided protein modeling and designing via homology and ab initio modeling, folding study using Molecular Dynamics (MD) methods and in silico mutation analysis.

Gene-environment interactions in heavy metal and pesticide carcinogenesis

Cancer is a complex disease involving a sequence of gene-environment interactions. Lifestyle, genetics, dietary factors, and environmental pollutants can increase the risk of cancer. Gene-environment interactions have been studied by a candidate-gene approach focusing on metabolism, DNA repair, and apoptosis. Here, we review the influence of gene-environment interactions in carcinogenesis, with emphasis on heavy metal and pesticide exposures.

Cancer chemoprevention by polyphenols and their potential application as nanomedicine.

Today cancer is a leading cause of death among the developed countries. Its highly complex nature makes it difficult to understand as it entails multiple cellular physiological systems such as cell signaling and apoptosis. The biggest challenges faced by cancer chemoprevention/chemotherapy is maintaining drug circulation and avoiding multidrug resistance. Overall there is modest evidence regarding the protective effects of nutrients from supplements against a number of cancers. Numerous scientific literatures available advocate the use of polyphenols for chemoprevention. Some groups have also suggested use of combination of nutrients in cancer prevention. However, we have yet to obtain the desired results in the line of cancer chemotherapy research. Nanotechnology can play a pivotal role in cancer treatment and prevention. Moreover, nanoparticles can be modified in various ways to prolong circulation, enhance drug localization, increase drug efficacy, and potentially decrease the chances of multidrug resistance. In this communication, we will cover the use of various polyphenols and nutrients in cancer chemoprevention. The application of nanotechnology in this regard will also be included. In view of available reports on the potential of nanoparticles, we suggest their usage along with different combination of nutrients as cancer chemotherapeutic agents.

Oxidative stress-mediated genotoxicity of wastewaters collected from two different stations in northern India

Oxidative stress-mediated genotoxicity of wastewaters taken from two different cities, Saharanpur (SWW) and Aligarh (AWW), were compared with a battery of short-term assays namely the Allium cepa genotoxicity test, the plasmid-nicking assay, and the Ames fluctuation test. Both test-water samples - when used undiluted - increased the frequency of chromosomal abnormalities and/or micronuclei and alterations in the mitotic index of root cells of Allium cepa. Bridges and fragmentation of the chromosome were the predominant effects of the Saharanpur water sample while the Aligarh sample induced mainly chromosome fragmentation. Single- and double-strand breaks were also observed in plasmid DNA treated with these test wastewaters. The plasmid-nicking assay performed on SWW resulted in linearization of plasmid DNA when 18μl was tested (in a total reaction volume of 20μl). However, with the same amount of AWW, all three forms of plasmid, viz. supercoiled, open circular and linear were observed. Supplementation with specific scavengers of reactive oxygen species (ROS) caused a significant decline in mutagenicity of test-water samples in all the tests, pointing at oxidative stress as the mediator of the observed genotoxicity. The role of heavy metals in the AWW-induced oxidative stress and that of phenolics in SWW cannot be ruled out.