Institute of Biomedical and Genetic Engineering IBGE

Islamabad, Pakistan

Institute of Biomedical and Genetic Engineering IBGE

Islamabad, Pakistan
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Popolo A.,University of Salerno | Pinto A.,University of Salerno | Daglia M.,University of Pavia | Nabavi S.F.,Baqiyatallah Medical Sciences University | And 2 more authors.
Seminars in Cancer Biology | Year: 2017

Diets containing high quantities of plant foods are linked with a decreased likelihood of incidence of cancer. Several common plant-based dietary components exert effects on DNA methylation levels, and can positively influence genome stability and the transcription of tumor suppressors and oncogenes. Indole-3-carbinol (I3C) is a substance present in vegetables of the Brassicaeae family, especially broccoli, white cabbage, Brussels sprouts and cauliflower. The in vivo biological effects of I3C are ascribed to a series of oligomeric products (including 3,3'-diindolylmethane), developed under acidic conditions. I3C is one of the many natural products and bioactive compounds found in foods which have recently received much attention for its potential effects in cancer prevention and treatment. In vitro studies report that I3C suppresses the proliferation of different tumor cells, including those isolated from breast, prostate, endometrium, and colon cancers. I3C resulted to be a potent in vivo chemopreventive agent for certain hormone-dependent cancers, including breast and cervical cancer. However, the mechanisms underlying these effects are not well defined. In this review, we have analysed recent literature on the use of indole derivatives against various forms of cancer, and have identified the main signalling pathways involved in their anti-cancer effect as PI3K/Akt/mTOR and the aryl hydrocarbon receptor. © 2017.

Alakbarzade V.,University of Exeter | Alakbarzade V.,University College London | Hameed A.,Institute of Biomedical and Genetic Engineering IBGE | Quek D.Q.Y.,National University of Singapore | And 17 more authors.
Nature Genetics | Year: 2015

The major pathway by which the brain obtains essential omega-3 fatty acids from the circulation is through a sodium-dependent lysophosphatidylcholine (LPC) transporter (MFSD2A), expressed in the endothelium of the blood-brain barrier. Here we show that a homozygous mutation affecting a highly conserved MFSD2A residue (p.Ser339Leu) is associated with a progressive microcephaly syndrome characterized by intellectual disability, spasticity and absent speech. We show that the p.Ser339Leu alteration does not affect protein or cell surface expression but rather significantly reduces, although not completely abolishes, transporter activity. Notably, affected individuals displayed significantly increased plasma concentrations of LPCs containing mono- and polyunsaturated fatty acyl chains, indicative of reduced brain uptake, confirming the specificity of MFSD2A for LPCs having mono-and polyunsaturated fatty acyl chains. Together, these findings indicate an essential role for LPCs in human brain development and function and provide the first description of disease associated with aberrant brain LPC transport in humans. © 2015 Nature America, Inc. All rights reserved.

PubMed | Copenhagen University, Institute of Biomedical and Genetic Engineering IBGE, University of Antwerp, National University of Singapore and 6 more.
Type: | Journal: Disease models & mechanisms | Year: 2017

A consanguineous family from Pakistan was ascertained with a novel deafness-dystonia syndrome with motor regression, ichthyosis-like features and signs of sensory neuropathy. By applying a combined strategy of linkage analysis and whole-exome sequencing in the presented family, a homozygous nonsense mutation, c.4G>T (p.Glu2*), in FITM2 was identified. FITM2 and its paralog FITM1 constitute an evolutionary conserved protein family involved in partitioning of triglycerides into cellular lipid droplets. Despite the role of FITM2 in neutral lipid storage and metabolism, no indications for lipodystrophy were observed in the affected individuals. In order to obtain independent evidence for the involvement of FITM2 in the human pathology, downregulation of the single Fitm ortholog, CG10671, in Drosophila melanogaster was pursued using RNA-interference. Characteristics of the syndrome, including progressive locomotor impairment, hearing loss and disturbed sensory functions, were recapitulated in Drosophila, which supports the causative nature of the FITM2 mutation. Mutation-based genetic counseling can now be provided to the family and insight is obtained in the potential impact of genetic variation in FITM2.

Kavaklioglu T.,Max Planck Institute for Psycholinguistics | Ajmal M.,Institute of Biomedical and Genetic Engineering IBGE | Hameed A.,Institute of Biomedical and Genetic Engineering IBGE | Francks C.,Max Planck Institute for Psycholinguistics
Neuropsychologia | Year: 2016

Pinpointing genes involved in non-right-handedness has the potential to clarify developmental contributions to human brain lateralization. Major-gene models have been considered for human handedness which allow for phenocopy and reduced penetrance, i.e. an imperfect correspondence between genotype and phenotype. However, a recent genome-wide association scan did not detect any common polymorphisms with substantial genetic effects. Previous linkage studies in families have also not yielded significant findings. Genetic heterogeneity and/or polygenicity are therefore indicated, but it remains possible that relatively rare, or even unique, major-genetic effects may be detectable in certain extended families with many non-right-handed members. Here we applied whole exome sequencing to 17 members from a single, large consanguineous family from Pakistan. Multipoint linkage analysis across all autosomes did not yield clear candidate genomic regions for involvement in the trait and single-point analysis of exomic variation did not yield clear candidate mutations/genes. Any genetic contribution to handedness in this unusual family is therefore likely to have a complex etiology, as at the population level. © 2015 Elsevier Ltd

Jan T.,International Islamic University, Islamabad | Iqbal J.,International Islamic University, Islamabad | Ismail M.,Institute of Biomedical and Genetic Engineering IBGE | Mansoor Q.,Institute of Biomedical and Genetic Engineering IBGE | And 2 more authors.
Applied Surface Science | Year: 2014

In this paper, ZnO nanorods doped with varying amounts of Ni have been prepared by chemical co-precipitation technique. Structural investigations provide the evidence that Ni is successfully doped into ZnO host matrix without having any secondary phases. Scanning electron microscopy (SEM) images reveal the formation of rodlike structure of undoped ZnO with average length and diameter of 1 μm and 80 nm, respectively. Raman spectroscopy results show that the E1 LO phonons mode band shifts to the higher values with Ni doping, which is attributed to large amount of crystal defects. Ni doping is also found to greatly influence the optical properties of ZnO nanorods. The influence of Ni doping on antibacterial characteristics of ZnO nanorods have been studied by measuring the growth curves of Escherichia coli (E. coli), Methicillin-resistant Staphylococcus aureus (S. aureus) and Pseudomonas aeruginosa (P. aeruginosa) bacteria in the presence of prepared nanorods. ZnO nanorods antibacterial potency is found to increase remarkably with Ni doping against S. aureus and P. aeruginosa microbials, which might possibly be due to the increase in reactive oxygen species (ROS) generation. Interestingly, it is observed that Ni doped ZnO nanorods completely eradicates these multi-drug resistant bacteria. © 2014 Elsevier B.V.

Zahoor A.,Institute of Biomedical and Genetic Engineering IBGE | Zahoor A.,International Islamic University, Islamabad | Mansoor Q.,Institute of Biomedical and Genetic Engineering IBGE | Farooqi A.A.,Institute of Biomedical and Genetic Engineering IBGE | And 3 more authors.
Cellular and Molecular Biology | Year: 2015

TRAIL mediated signaling in cancer cells has emerged as one amongst the most deeply studied molecular phenomenon. Data obtained through genetic studies has highlighted highly polymorphic nature of DR4 and in accordance with this concept, we aimed to investigate the association between Colorectal cancer and polymorphisms in TRAIL and DR4 gene. We selected 100 patients with colorectal cancer and 100 healthy, sex and age matched volunteers randomly. C626G and A1322G in DR4 gene were analyzed using Polymerase Change Reaction (PCR)-Restriction Fragment Length Polymorphism (RFLP) and Amplification Refractory Mutation System (ARMS) techniques. PCR-RFLP was used to study TRAIL 1595 C>T. TRAIL gene 1595 C>T genotypes percentage in colorectal cancer patients was statistically non-significant. CC was 43% in patients and 50% in controls. CT was 45% in patients and 43% in controls. TT was 12% in patients and 7% in controls. C allele was 0.655% in cancer patients and 0.715% in controls. T allele was 0.345% in patients and 0.285% in controls. DR4 gene 626 C>G genotypes percentage analysis indicated that CC was 28% in patients and 2% in controls. GC was 42% in patients and 40% in controls. GG was 30% in patients and 58% in controls. CC was statistically significant (p=0.00000207) in cancer patients. C allele was 0.49% in patients and 0.22% in controls. G allele was 0.51% in patients and 0.78% in controls. For DR4 A1322G, homozygous GG genotype was 36% in the patients and in controls. There was statistically insignificant difference (p> 0.05). The heterozygous GT genotype was 30% in patients and 29% in controls. This difference was statistically insignificant (p value > 0.05). Similarly, the homozygous genotype TT of the minor allele was (35%) in controls and patients (34 %). This difference was also statistically insignificant (p value > 0.05). C allele was 0.51% in patients and 0.5% in controls. T allele was 0.49% in patients and 0.495% in controls. Future studies must converge on a larger sample size, sporadic mutations of DR4 and TRAIL and expression profiling. © 2015.

Jan T.,International Islamic University, Islamabad | Iqbal J.,International Islamic University, Islamabad | Ismail M.,Institute of Biomedical and Genetic Engineering IBGE | Mahmood A.,National Institute of Lasers and Optronics
Journal of Applied Physics | Year: 2014

Here, synthesis, structural, morphological, Raman, optical properties and antibacterial activity of undoped and Ag doped ZnO nanorods by chemical co-precipitation technique have been reported. Structural analysis has revealed that Ag doping cannot deteriorate the structure of ZnO and wurtzite phase is maintained. Lattice constants are found to be decreased with the Ag doping. Fourier transform infrared and Raman spectroscopy also confirm the X-ray diffraction results. Scanning electron microscopy results have demonstrated the formation of ZnO nanorods with average diameter and length of 96 nm and 700 nm, respectively. Raman spectroscopy results suggest that the Ag doping enhances the number of defects in ZnO crystal. It has been found from optical study that Ag doping results in positional shift of band edge absorption peak. This is attributed to the successful incorporation of Ag dopant into ZnO host matrix. The antibacterial activity of prepared nanorods has been determined by two different methods and compared to that of undoped ZnO nanorods. Ag doped ZnO nanorods exhibit excellent antibacterial activity as compared to that of undoped ZnO nanorods. This excellent antibacterial activity may be attributed to the presence of oxygen vacancies and Zn2+ interstitial defects. Our preliminary findings suggest that Ag doped ZnO nanorods can be used externally to control the spreading of infections related with tested bacterial strains. © 2014 AIP Publishing LLC.

Farooqi A.A.,Rashid Latif Medical College RLMC | Bhatti S.,University of Health Sciences, Lahore | Ismail M.,Institute of Biomedical and Genetic Engineering IBGE
Cancer Cell International | Year: 2012

Cancer is a multifaceted molecular disorder that is modulated by a combination of genetic, metabolic and signal transduction aberrations, which severely impair the normal homeostasis of cell growth and death. Accumulating findings highlight the fact that different genetic alterations, such as mutations in tumor suppressor genes, might be related to distinct and differential sensitivity to targeted therapies. It is becoming increasingly apparent that a multipronged approach that addresses genetic milieu (alterations in upstream and/or parallel pathways) eventually determines the response of individual tumors to therapy. Cancerous cells often acquire the ability to evade death by attenuating cell death pathways that normally function to eliminate damaged and harmful cells. Therefore impaired cell death nanomachinery and withdrawal of death receptors from cell surface are some of major determinants for the development of chemotherapeutic resistance encountered during treatment. It is therefore essential to emphasize underlying factors which predispose cells to refractoriness against TRAIL mediated cell death pathway and the relevant regulatory components involved. We bring to limelight the strategies to re-sensitize TRAIL resistant cells via vitamins to induce apoptosis. © 2012 Farooqi et al.; licensee BioMed Central Ltd.

Shaikh R.,University of Karachi | Shahid S.M.,University of Karachi | Mansoor Q.,Institute of Biomedical and Genetic Engineering IBGE | Ismail M.,Institute of Biomedical and Genetic Engineering IBGE | Azhar A.,University of Karachi
JRAAS - Journal of the Renin-Angiotensin-Aldosterone System | Year: 2014

Diabetes mellitus (DM) has been a growing epidemic worldwide and poses a major socio-economic challenge. The leading cause of DM death is nephropathy due to end-stage renal disease (ESRD). This study aims to identify the possible association of I/D variants of the ACE gene and M268T (rs699) of the AGT gene of renin-angiotensin-aldosterone system (RAAS). Materials and methods: Study subjects include 115 patients with DM, 110 with diabetic nephropathy (DN) and 110 controls. Fasting blood samples were collected for biochemical analyses and PCR amplification of specific regions of the ACE and AGT genes using primers. Results: The distribution of ACE (I/D) II 28.8%, ID 35.6% and DD 35.6% while in DN II 24.5%, ID 41% and DD 34.5%. The AGT (M268T) genotypes were distributed in DM as TT 30.4%, MT 66.9% and MM 2.6% while in DN subjects TT 56.4%, MT 42.7% and MM 0.9%. Conclusion: Significant differences were observed in the DD genotype and D allele of the ACE gene and the TT genotype and T allele of AGT genes between diabetic patients with and without nephropathy. The study may conclude that the D allele polymorphism in the ACE gene and the T allele polymorphism in AGT gene may be considered as genetic risk factors for the development of nephropathy in diabetes. © 2014 The Author(s).

Farooqi A.A.,Institute of Biomedical and Genetic Engineering IBGE | Siddik Z.H.,University of Houston
Cell Biochemistry and Function | Year: 2015

Platelet-derived growth factor (PDGF)-mediated signalling has emerged as one of the most extensively and deeply studied biological mechanism reported to be involved in regulation of growth and survival of different cell types. However, overwhelmingly increasing scientific evidence is also emphasizing on dysregulation of spatio-temporally controlled PDGF-induced signalling as a basis for cancer development. We partition this multi-component review into recently developing understanding of dysregulation PDGF signalling in different cancers, how PDGF receptors are quantitatively controlled by microRNAs. Moreover, we also summarize most recent advancements in therapeutic targeting of PDGFR as evidenced by preclinical studies. Better understanding of the PDGF-induced intracellular signalling in different cancers will be helpful in catalysing the transition from a segmented view of cancer biology to a conceptual continuum. © 2015 John Wiley & Sons, Ltd.

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