Most of the exogenous and endogenous chemical compounds are metabolized by enzymes of xenobiotic processing pathways, including the phase I cytochrome p450 species. Carcinogens and their metabolites are generally detoxified by phase II enzymes like glutathione-S-transferases (GST). The balance of enzymes determines whether metabolic activation of pro-carcinogens or inactivation of carcinogens occurs. Under certain conditions, deregulated expression of xenobiotic enzymes may also convert endogenous substrates to metabolites that can facilitate DNA adduct formation and ultimately lead to cancer development. In this study, we aimed to test the association between deregulation of metabolizing genes and brain tumorigenesis. The expression profile of metabolizing genes CYP1A1 and GSTP1 was therefore studied in a cohort of 36 brain tumor patients and controls using Western blotting. In a second part of the study we analyzed protein expression of GSTs in the same study cohort by ELISA. CYP1A1 expression was found to be significantly high (p<0.001) in brain tumor as compared to the normal tissues, with ~4 fold (OR=4, 95%CI=0.43-37) increase in some cases. In contrast, the expression of GSTP1 was found to be significantly low in brain tumor tissues as compared to the controls (p<0.02). This down regulation was significantly higher (OR=0.05, 95%CI=0.006-0.51; p<0.007) in certain grades of lesions. Furthermore, GSTs levels were significantly down-regulated (p<0.014) in brain tumor patients compared to controls. Statistically significant decrease in GST levels was observed in the more advanced lesions (III-IV, p<0.005) as compared to the early tissue grades (I-II). Thus, altered expression of these xenobiotic metabolizing genes may be involved in brain tumor development in Pakistani population. Investigation of expression of these genes may provide information not only for the prediction of individual cancer risk but also for the prevention of cancer.
In this work, an evolving Linked Quantum Register has been introduced, that are group vector of binary pair of genes, uses local topological space to represent those nodes. The optimal points of node for topology control have high connectivity and have low energy consumption, and have interference at low. The register works in higher dimension. In this modeling order-2 Quantum Inspired Genetic Algorithm has been used and higher order can be used to achieve greater versatility in topology control of nodes. Numerical result has been obtained, analysis is done as how the result has previously been obtained with Quantum Genetic Algorithm and results are compared too. For future work, metrics for LQR are hinted that would exploit the algorithm to work in more computational intensive problem.
Exposure to wood smoke leads to mucosal irritation and physiological and neurological abnormalities in human.Blood samples along with histories were taken from 100(50Tandoor occupants and 50 controls) male individualsliving in the same locality. SYSMIX KX-21 (Japan) and Shimadzu Double Beam Spectrophotometer 1700 Pharma (Japan) were used for blood profiling and serum biochemistry. In workers, blood cholesterol was 131 ± 4.8 mg/dl, triglyceride was 125 ± 10mg/dl, and serum glutamate pyruvate transaminase level was 68 ± 2.4IU/L and glucose level was 113 ± 2.1 mg/dl. The total red blood cell count was 5.6 ± 0.035mill/cmm, hemoglobin level was15 ± 0.054mg/dl, hematocrit value was49 ± 0.22 mg/dl, mean corpuscular volume was 86 ± 0.22 fl,mean corpuscular hemoglobin was 31 ± 0.12 pg, mean corpuscular hemoglobin concentration was 35 ± 0.12gm/dl, neutrophils were 77 ± 0.50%, lymphocytes were 45 ± 1.0 %, eosinophilswere6.0 ± 0.14%, monocytes were 7.7 ± 0.19 %, total leukocyte count were 11014 ± 115/cmm, and platelets were235864 ± 5491 /cmm. In control group the blood cholesterol, triglyceride, serum glutamate pyruvate transaminase and glucose level was111 ± 2.4mg/dl,97 ± 1.5mg/dl, 28 ± 1.1IU/L and 101 ± 1.2 mg/dl respectively, while thetotal red blood cell count, hemoglobin level, hematocrit value, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobinconcentration, neutrophils, lymphocytes, eosinophils, monocytes, leukocyte, and platelets were4.3 ± 0.027mil/cmm, 12 ± 0.064 mg/dl, 38 ± 0.11mg/dl, 75 ± 0.30fl, 25 ± 0.37pg, 31 ± 0.11gm/dl, 56 ± 0.82%, 34 ± 1.0, 3.1 ± 0.20%, 4.2 ± 0.12%, 6573 ± 125, and 169162 ± 2454 /cmm respectively.The levels in both groups were statistically compared using t test and the p value was determined.The results showed that there was significant increase in blood biochemical parameters as well as in complete blood count in workers as compared to control and are therefore at more risk to heart, lungs and blood diseases.
ABSTRACT. Cadmium (Cd) is produced mainly as a by-product of zinc mining. In Thailand, the largest zinc mine is located in the Mae Sot district, Tak Province. Samples of Monopterus albus were collected from paddy fields in 4 sites, three downstream and one upstream from the zinc mine. The upstream site was considered to be uncontaminated while the three downstream sites were considered to be contaminated with Cd. Studies on the accumulation level of cadmium were conducted on the liver of the fish using the atomic absorption spectrophotometer technique. The metallothionein (MT) gene expression level in the liver, as a potential biomarker for long-term Cd exposure in their natural habitat, was also assessed. The level of hepatic MT gene expression was performed by quantitative real-time PCR. The result showed that Cd accumulation in the liver was much higher in swamp eels collected from the downstream sites when compared to those collected from the upstream site. The hepatic MT level in the upstream site was 0.75-fold, 2 M. Wahid et al. Genetics and Molecular Research 16 (3): gmr16039748 while the other three downstream sites were 0.36-, 4.44-and 0.94-fold. There is no parallel correlation between hepatic cadmium levels and hepatic MT gene expression. This study then suggests that MT gene expression biomarkers might be not suitable for swamp eels with prolonged exposure to Cd.
Introduction: Lack of efficient collateralisation during vascular occlusion leads to tissue ischemia in coronary, peripheral and cerebrovascular disease. Patients with peripheral, coronary, and cerebrovascular disease have elevated levels of the anti-angiogenic isoform of VEGF (VEGF-A 165 b), which correlate with poorer outcomes. In experimental animals, VEGF-A 165 b neutralisation improves blood flow and collateralisation after femoral or coronary artery ligation. Hypothesis: We tested the hypothesis that a potent, high affinity, humanised neutralising antibody to VEGF-A 165 b could have therapeutic potential in models of cardiovascular disease. Methods: A mouse monoclonal antibody to VEGF-A 165 b was humanised by cloning and site directed mutagenesis. Multiple clones were screened, and one with high affinity (measured by biolayer interferometry) was amplified. The efficacy in vitro was tested using endothelial cell migration assays and in vivo using the hindlimb ischemia (HLI) model in C57Bl6 mice fed a high fat high sucrose (HFHS) diet, and in Zucker Diabetic Fatty rats. Results: One clone (HC4LC2) had a VEGF-A 165 b affinity of 600pM. 0.3μg/ml of this clone reversed the inhibitory effect of recombinant human VEGF-A 165 b (31±4%, N=6 of VEGF-A 165 a alone) on migration of endothelial cells to 40ng/ml rhVEGF-A 165 a (89±9% N=3). Human monocyte dependent inhibition of VEGF-A 165 a mediated migration was dose dependently reversed by HC4LC2 (EC50, 55ng/ml, N=9 per concentration). HLI in HFHS mice impaired blood flow after 28 days in IgG treated mice (70±7.7% of pre-ischemic blood flow, N=6), which was restored to normal (93.3±5.5, p<0.05, N=8) by intraperitoneal injection of 1mg/kg HC4LC2. Blood flow recovery after HLI was also seen in ZDF rats treated with HC4LC2 (106±16% of pre-ischemic flow, N=5) compared with IgG treated animals (76±.9%, N=5, p<0.05, two-way ANOVA, all values mean ±SEM). Conclusions: These results indicate that HC4LC2 is a humanised, high affinity neutralising antibody to VEGF-A 165 b that could have therapeutic potential for patients with cardiovascular disease, by enhancing collateral formation.
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