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Ambreen F.,Quaid-i-Azam University | Ismail M.,Institute of Biomedical and Genetic Engineering | Qureshi I.Z.,Quaid-i-Azam University
Molecular Vision | Year: 2015

Purpose: To study the association of serum levels of inflammatory mediators and angiogenic factors with genetic polymorphism in Pakistani age-related macular degeneration (AMD) patients. Methods: This was a cross-sectional and case-control study that included 90 AMD patients diagnosed through slit-lamp examination, fundoscopy, and ocular coherence tomography. For reference and comparison purposes, 100 healthy agematched subjects (controls) were also recruited. IL-6, IL-8, VEGF, and CRP levels were estimated in the serum samples of patients and control subjects. Using restriction fragment length polymorphism, single nucleotide polymorphisms were studied in IL-6 (rs1800795, rs1800796, rs1800797), IL-8 (rs4073, rs2227306, rs2227543), VEGF (rs3025039, rs699947), and CRP genes (rs1205, rs1130864). Since the data were obtained from a sample population, the Box-Cox transformation algorithm was applied to reduce heterogeneity of error. Multivariate analyses of variance (M-ANOVA) were applied on the transformed data to investigate the association of serum levels of IL-6, IL-8, VEGF, and CRP with AMD. Genotype and allele frequencies were compared through χ2 tests applying Hardy-Weinberg equilibrium. The serum concentrations of IL-6 and IL-8, VEGF, and CRP between homozygotes and heterozygotes were compared through one-way ANOVA. Significance level was p<0.05. Results: Compared to control subjects, serum IL-6 (p<0.0001), IL-8 (p<0.0001), VEGF (p<0.0001), and CRP (p<0.0001) levels were significantly elevated in the AMD patients. For rs1800795, patients with the GG genotype showed significan-t ly raised levels of IL-6 compared to those with GC and CC genotypes (p<0.0001). Serum IL-8 levels were significantly higher in patients with the GG genotype compared to the GC and CC genotypes for the single nucleotide polymorphism (SNP) rs2227543 (p<0.002). Similarly, significantly higher VEGF levels were detected for genotype TT for rs3025039 SNP (p<0.038). However, no significant alteration in serum CRP levels was detected in hetero- or homozygotes for rs1205 and rs1130864 SNPs. Conclusions: Serum IL-6, IL-8, and VEGF levels are substantially increased in AMD, and the levels coincide with polymorphism in the respective gene. No such relationship appears to exist with regard to SNPs of CRP. © 2015 Molecular Vision. Source

Farooqi A.A.,Rashid Latif Medical College RLMC | Nawaz A.,The University of Lahore | Javed Z.,The University of Lahore | Bhatti S.,The University of Lahore | Ismail M.,Institute of Biomedical and Genetic Engineering
Archivum Immunologiae et Therapiae Experimentalis | Year: 2013

It is a well-acclaimed fact that proteins expressed as a consequence of oncogenic fusions, mutations or amplifications can facilitate ectopic protein-protein interactions that re-wire signal dissemination pathways, in a manner that escalates malignancy. BCR-ABL-mediated signal transduction cascades in leukemic cells are assembled and modulated by a finely controlled network of protein-protein interactions, mediated by characteristic signaling domains and their respective binding motifs. BCR-ABL functions in a cell context-specific and cell type-specific manner to integrate signals that affect uncontrolled cellular proliferation. In this review, we draw attention to the recent progress made in outlining resistance against TRAIL-mediated apoptosis and diametrically opposed roles of miRNAs in BCR-ABL-positive leukemic cells. BCR-ABL governs carcinogenesis through well-organized web of antiapoptotic proteins and over-expressed oncomirs which target death receptors and pro-apoptotic genes. Set of oncomirs which inversely correlate with expression of TRAIL via suppression of SMAD is an important dimension which is gradually gaining attention of the researchers. Contrary to this, some current findings show a new role of BCR-ABL in nucleus with spotlight on apoptosis. It seems obvious that genetic heterogeneity of leukemias poses therapeutic challenges, and pharmacological agents that target components of the cancer promoting nano-machinery still need broad experimental validation to be considered competent as a component of the therapeutic arsenal for this group of diseases. Rapidly developing technologies are empowering us to explain the molecular "nature" of a patient and/or tumor and with this integration of personalized medicine, with maximized efficacy, cost effectiveness will hopefully improve survival chances of the patient. © 2012 L. Hirszfeld Institute of Immunology and Experimental Therapy, Wroclaw, Poland. Source

Matin A.,Institute of Biomedical and Genetic Engineering | Jung S.-Y.,Namseoul University
Korean Journal of Parasitology | Year: 2011

The existence of symbiotic relationships between Acanthamoeba and a variety of bacteria is well-documented. However, the ability of Acanthamoeba interacting with host bacterial pathogens has gained particular attention. Here, to understand the interactions of Escherichia coli K1 and E. coli K5 strains with Acanthamoeba castellanii trophozoites and cysts, association assay, invasion assay, survival assay, and the measurement of bacterial numbers from cysts were performed, and nonpathogenic E. coli K12 was also applied. The association ratio of E. coli K1 with A. castellanii was 4.3 cfu per amoeba for 1 hr but E. coli K5 with A. castellanii was 1 cfu per amoeba for 1 hr. By invasion and survival assays, E. coli K5 was recovered less than E. coli K1 but still alive inside A. castellanii. E. coli K1 and K5 survived and multiplied intracellularly in A. castellanii. The survival assay was performed under a favourable condition for 22 hr and 43 hr with the encystment of A. castellanii. Under the favourable condition for the transformation of trophozoites into cysts, E. coli K5 multiplied significantly. Moreover, the pathogenic potential of E. coli K1 from A. castellanii cysts exhibited no changes as compared with E. coli K1 from A. castellanii trophozoites. E. coli K5 was multiplied in A. castellanii trophozoites and survived in A. castellanii cysts. Therefore, this study suggests that E. coli K5 can use A. castellanii as a reservoir host or a vector for the bacterial transmission. © 2011, Korean Society for Parasitology. Source

Raza R.,COMSATS Institute of Information Technology | Matin A.,Institute of Biomedical and Genetic Engineering | Sarwar S.,COMSATS Institute of Information Technology | Barsukova-Stuckart M.,Jacobs University Bremen | And 3 more authors.
Dalton Transactions | Year: 2012

The biological significance of polyoxometalates is well renowned owing to their anticancer, antiviral and antibiotic properties. Here another therapeutic aspect of polyoxometalates has been explored as alkaline phosphatase inhibitors along with the remarked anticancer and amoebicidal properties. Synthesis and inhibitory studies of a set of seven polyoxotungstates against two major isozymes of alkaline phosphatase i.e. tissue specific and tissue non-specific alkaline phosphatase revealed their promising activity as alkaline phosphatase inhibitors. All compounds exhibited alkaline phosphatase inhibitory potency in nanomolar ranges. For tissue specific alkaline phosphatase, Na 10[H2W12O42]·27H 2O (A6) was found to be the most potent inhibitor (Ki value 313 ± 7 nM), while for tissue non-specific alkaline phosphatase Na33[H7P8W48O184] ·92H2O (A3) showed the highest inhibition potency (K i values 135 ± 10 nM). Moreover cytotoxicity evaluation of these compounds against lung carcinoma cells and immortalized human corneal epithelial cells demonstrated their anticancer potential with no cytotoxic effects on normal human cell lines. All anticancer drugs result in an impaired immune system and such immunocompromised persons become vulnerable to opportunistic infections specially Acanthamoeba which causes granulomatous amoebic encephalitis (GAE) which almost always results in death. The exclusive property of our tested polyoxotungstates is their strong amoebicidal activity against Acanthamoeba. Hence the study reveals a new window towards cancer therapy with the combined control of elevated levels of alkaline phosphatase and granulomatous amoebic encephalitis in cancer patients. © 2012 The Royal Society of Chemistry. Source

Liaquat A.,Quaid-i-Azam University | Shauket U.,Institute of Biomedical and Genetic Engineering | Ahmad W.,Quaid-i-Azam University | Javed Q.,Quaid-i-Azam University
Clinical Chemistry and Laboratory Medicine | Year: 2015

Background: Inflammation plays an imperative role in the etiology of cardiovascular diseases (CVD). The role of cytokines in the development and progression of idiopathic dilated cardiomyopathy (IDCM) is still uncertain. The current study was conducted to evaluate the association of tumor necrosis factor-α (TNF-α)-238G/A and IL-6-572G/C gene polymorphism with IDCM in a Pakistani population. Methods: IDCM cases (n=250) and healthy controls (n=300) were genotyped using PCR-RFLP. Results: The variant genotypes of both the loci showed significant differences between patients and controls (p<0.05). However,-238G/A polymorphism did not show association with the disease in the presence of covariates. We also conducted a meta-analysis of both the loci with regards to CVD in accordance with the Prisma checklist. No significant relation of the TNF-α-238G/A polymorphism with CVD was found; however, this single nucleotide polymorphism (SNP) showed an association with the disease in the Asian population after subgroup analysis (p=0.01). Whereas, the IL-6-572G/C polymorphism showed that the variant genotype (GC+CC) was associated with higher risk of CVD in contrast to the GG genotype. Furthermore, subgroup meta-analysis demonstrated a significant association of the-572 polymorphism with CVD in Asians, but no association was observed among Western populations with this SNP. Conclusions: Our findings support an association between the IL-6-572G/C polymorphism and IDCM risk. The role of the TNF-α-238G/A polymorphism in IDCM is still unclear. Further studies are warranted to determine the serum cytokine levels in relation to the cytokines' SNP in diverse ethnic groups to ascertain the molecular basis of the disease pathology. © 2015 by De Gruyter 2015. Source

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