Publications by authors named "Aneesa Sultan"

22 Publications

  • Page 1 of 1

Melatonin abated Bisphenol A-induced neurotoxicity via p53/PUMA/Drp-1 signaling.

Environ Sci Pollut Res Int 2021 Jan 5. Epub 2021 Jan 5.

Signal Transduction Laboratory, Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, 45320, Pakistan.

Bisphenol A (BPA), an endocrine disruptor, is widely used in the manufacture of different daily life products. Accumulating evidence supports the association between the increasing incidence of neurodegenerative diseases and the BPA level in the environment. In the present study, we aimed to evaluate the neuroprotective role of melatonin against BPA-induced mitochondrial dysfunction-mediated apoptosis in the brain. Herein, adult Sprague Dawley rats were administrated (subcutaneously) with BPA (100 μg/kg BW, 1 mg/kg BW, and 10 mg/kg BW) and melatonin (4 mg/kg BW) for 16 days. Our results showed BPA exposure significantly increased the oxidative stress as demonstrated by increased free radicals (ROS), TBARs level, disrupted cellular architecture, and decreased antioxidant enzymes including SOD, CAT, APX, POD, and GSH levels. Additionally, BPA treatment increased the expression of PUMA, p53, and Drp-1 resulting in apoptosis in the brain tissue of rats. However, melatonin treatment significantly attenuated BPA-induced toxic effects by scavenging ROS, boosting antioxidant enzyme activities, and interestingly enervated brain apoptosis by normalizing p53, PUMA, and Drp-1 expressions at both transcriptional and translational level. Moreover, the brain tissue histology also revealed the therapeutic potential of melatonin by normalizing the cellular architecture. Conclusively, our finding suggests that melatonin could alleviate oxidative stress and mitochondrial dysfunction-linked apoptosis, rendering its neuroprotective potential against BPA-induced toxicity.
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http://dx.doi.org/10.1007/s11356-020-12129-5DOI Listing
January 2021

Pistacia integerrima alleviated Bisphenol A induced toxicity through Ubc13/p53 signalling.

Mol Biol Rep 2020 Sep 8;47(9):6545-6559. Epub 2020 Aug 8.

Signal Transduction Lab, Department of Biochemistry, Faculty of Biological Sciences, Quaid-I-Azam University, Islamabad, 45320, Pakistan.

Exposure to environmental toxicants such as Bisphenol A (BPA) has raised serious health issues globally particularly in developing countries. It is ubiquitously used in the manufacturing of canned food and feeding bottles. BPA generated reactive oxygen species can lead to several diseases including cardiotoxicity. However, the endpoints stimulated in BPA cardiotoxicity yet need to be investigated. The current study was aimed to investigate the underlying molecular pathways which may contribute in revealing the protective effects of Pistacia integerrima against BPA induced oxidative stress. The dose of 100 µg/kg BW of BPA, 200 mg/kg BW P. integerrima, and 4 mg/kg BW melatonin was administered to Sprague Dawley rats. Present results of western blotting and qRT-PCR showed the increased expression of p53, PUMA and Drp1, while downregulation of Ubc13 in heart tissues of BPA treated group whereas the levels were reversed upon treatment with P. integerrima. The role of BPA in heart tissue apoptosis was further confirmed by the increased level of P-p53, cytochrome C and disrupted cellular architecture whereas the P. integerrima has shown its ameliorative potential by mitigating the adverse effects of BPA. Moreover, the oxidant, antioxidant, lipid, and liver markers profile has also revealed the therapeutic potential of P. integerrima by maintaining the levels in the normal range. However, melatonin has also manifested the normalized expression of apoptotic markers, biochemical markers, and tissue architecture. Conclusively, the data suggest that P. integerrima may be a potential candidate for the treatment of BPA induced toxicity by neutralizing the oxidative stress through Ubc13/p53 pathway.
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http://dx.doi.org/10.1007/s11033-020-05706-xDOI Listing
September 2020

Apoptosis of Leukemia Cells by Ocimum basilicum Fractions Following TNF alpha Induced Activation of JNK and Caspase 3.

Curr Pharm Des 2019 ;25(34):3681-3691

Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.

Purpose: Leukemia, one of the major cancers, affects a large proportion of people around the world. Better treatment options for leukemia are required due to a large number of side effects associated with current therapeutic regimens. In the present study, we sought to determine the pathway of triggering apoptosis of leukemic cells by Ocimum basilicum (O. basilicum) plant extract.

Materials/methods: Methanolic extract of the O. basilicum plant material was prepared. The crude extract was fractionated into several fractions through column chromatography using ethyl acetate and n-hexane as eluting solvents. Cell viability of leukemic cells was assessed via Cell titer GLO assay and apoptosis was measured through Annexin V/PI staining. Two apoptotic molecules JNK and caspases were analyzed through western blotting while pro-inflammatory cytokines TNFα, CCL2 and CXCL8 using qPCR. Fractions were characterized through LC-MS.

Results: The most potent with lowest IC50 values among the fractions were BF2 (2:8 n-hexane:ethyl acetate) and BF3 (3:7 n-hexane:ethyl acetate). Cytotoxicity was associated with apoptosis. Apoptosis was found caspasedependent and P-JNK activation was detected sustained. A significant increase in the level of TNF α and a decrease in the level of CXCL8 were observed in BF2 and BF3 treated cells.

Conclusion: The fractions of O. basilicum extract were found to kill cells following JNK pathway activation. Excellent results were obtained with BF2 and BF3 probably due to predominant Epicatechin and Cinnamic acid derivatives in these fractions.
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http://dx.doi.org/10.2174/1381612825666191011100826DOI Listing
June 2020

Genetic Polymorphism of CYP2C19 in Pakistani Population.

Iran J Pharm Res 2019 ;18(2):1097-1102

Institute of Biomedical and Genetic Engineering, 24 Mauve Area, G-9/1, Islamabad, Pakistan.

CYP2C19 polymorphism is associated with pretreatment drug response prediction, metabolism, and disposition. Pakistan consists of a population comprising of various ethnic groups residing in different regions of the country each claiming diverse ethnic origins. The identification of CYP450 genotypic composition of these populations is therefore necessary to avoid adverse drug reactions in these individuals. The main objective of the study was to investigate the prevalence of CYP2C19*2 and CYP2C19*17 alleles in these ethnic groups. The study was conducted on one thousand and twenty-eight (n = 1028) healthy volunteers from nine ethnic groups of Pakistan namely Brusho (n = 28), Hazara (n = 102), Kalash (n = 64), Pathan (n = 170), Punjabi (n = 218), Saraiki (n = 59), Brahui (n = 118), Parsi (n = 90), and Sindhi (n = 179). DNA was extracted from leukocytes and analyzed by allele specific amplification polymerase chain reaction (ASA-PCR). Multi allelic polymorphism of CYP2C19 led to four distinct phenotypes identified as extensive metabolizer (EM), poor metabolizer (PM), intermediate metabolizer (IM), and ultra-rapid metabolizer (UM). Over all, the percentage of predicted poor metabolizer allele was 29.0% compared to UM allele (23.70%). Among the studied groups, Saraiki and Brahui showed highest percentage of PM allele (40%, 36%) whereas Parsi and Hazara had highest percentage of UM allele (37% and 30% respectively). In conclusion, the high allele frequency of PM (CYP2C19*2 and *17) in Pakistani population led to the recommendation of a pre-treatment test to monitor drug response and dosage (personalized medicine) to avoid post-treatment adverse drug reactions.
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http://dx.doi.org/10.22037/ijpr.2019.1100644DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6706708PMC
January 2019

Analysis of NT-proBNP and uric acid due to left ventricle hypertrophy in the patients of aortic valve disease.

Pak J Med Sci 2019 Jan-Feb;35(1):183-188

Iram Murtaza, PhD. Signal Transduction Lab, Department of Bio-Chemistry, Faculty of Biological Sciences, Quaid-I-Azam University Islamabad, Islamabad, Pakistan.

Objective: To evaluate the concentration of N terminal proBNP (NT-proBNP) and partially the serum uric acid in the severe condition of aortic valve dysfunction for assessment of left ventricle hypertrophy.

Methods: The study was conducted in the signal transduction lab department of biochemistry Quaid-I-Azam University, Islamabad from September 2013 to February 2017. NT-proBNP and serum uric acid were measured in one hundred patients of aortic valve dysfunction. The patients were divided into three main groups: 1) Aortic stenosis, 2) Aortic regurgitation, and 3) Aortic stenosis with Aortic regurgitation. The results were compared between disease and controls groups.

Results: High level of plasma NT-proBNP was detected in all the three disease groups of aortic valve (stenosis, p<0.001), (regurgitation, p<0.001) and (stenosis with regurgitation, p<0.001). In addition, non-significantly increased level of serum uric acid was also observed in left ventricle hypertrophy in all the three respective disease groups of aortic valve.

Conclusion: Increased secretion of NT-proBNP during cardiac remodeling can be related to the severity of left ventricle hypertrophy due to aortic valve abnormality in all the disease groups of severe stenosis, severe regurgitation, and combine disease condition of severe stenosis and severe regurgitation. However, non-significant increase in uric acid concentration is also identified which may be due to one of the factors involved in left ventricle hypertrophy in all the three disease groups of aortic valve. The interaction of uric acid with NT-proBNP during cardiac remolding due to aortic valve dysfunction is still not clear.
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http://dx.doi.org/10.12669/pjms.35.1.148DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6408659PMC
March 2019

Interplay of N acetyl cysteine and melatonin in regulating oxidative stress-induced cardiac hypertrophic factors and microRNAs.

Arch Biochem Biophys 2019 01 12;661:56-65. Epub 2018 Nov 12.

Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam, University, Islamabad, 45320, Pakistan. Electronic address:

Early and specific diagnosis of oxidative stress linked diseases as cardiac heart diseases remains a major dilemma for researchers and clinicians. MicroRNAs may serve as a better tool for specific early diagnostics and propose their utilization in future molecular medicines. We aimed to measure the microRNAs expressions in oxidative stress linked cardiac hypertrophic condition induced through stimulants as Endothelin and Isoproterenol. Cardiac hypertrophic animal models were confirmed by BNP, GATA4 expression, histological assays, and increased cell surface area. High oxidative stress (ROS level) and decreased antioxidant activities were assessed in hypertrophied groups. Enhanced expression of miR-152, miR-212/132 while decreased miR-142-3p expression was observed in hypertrophic condition. Similar pattern of these microRNAs was detected in HL-1 cells treated with HO. Upon administration of antioxidants, the miRNAs expression pattern altered from that of the cardiac hypertrophied model. Present investigation suggests that oxidative stress generated during the cardiac pathology may directly or indirectly regulate anti-hypertrophy pathway elements through microRNAs including antioxidant enzymes, which need further investigation. The down-regulation of free radical scavengers make it easier for the oxidative stress to play a key role in disease progression.
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http://dx.doi.org/10.1016/j.abb.2018.11.007DOI Listing
January 2019

Epidemiological, clinical and genetic characterization of aplastic anemia patients in Pakistan.

Ann Hematol 2019 Feb 13;98(2):301-312. Epub 2018 Nov 13.

Department of Biochemistry, Quaid-i-Azam University, Islamabad, 44000, Pakistan.

Aplastic anemia (AA) is the most serious non-malignant blood disorder in Pakistan, ranked second in prevalence, after thalassemia. We investigated various epidemiological, clinical, and genetic factors of AA in a Pakistani cohort of 214 patients reporting at our hospital between June 2014 and December 2015. A control group of 214 healthy subjects was included for comparison of epidemiological and clinical features. Epidemiological data revealed 2.75-fold higher frequency of AA among males. A single peak of disease onset was observed between ages 10 and 29 years followed by a steady decline. AA was strongly associated with lower socioeconomic profile, rural residence, and high rate of consanguineous marriages. Serum granulocyte colony-stimulating factor and thrombopoietin levels were significantly elevated in AA patients, compared to healthy controls (P < 0.0001), while there was no statistical significance in other nine cytokine levels screened. Allele frequencies of DRB1*15 (56.8%) and DQB1*06 (70.3%) were predominantly high in AA patients. Ten mutations were found in TERT and TERC genes, including two novel mutations (Val526Ala and Val777Met) in exons 3 and 7 of TERT gene. Despite specific features of the AA cohort, this study suggests that epidemiologic and etiologic factors as well as host genetic predisposition exclusively or cooperatively trigger AA in Pakistan.
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http://dx.doi.org/10.1007/s00277-018-3542-zDOI Listing
February 2019

Data of expression status of miR- 29a and its putative target mitochondrial apoptosis regulatory gene DRP1 upon miR-15a and miR-214 inhibition.

Data Brief 2018 Feb 20;16:1000-1004. Epub 2017 Dec 20.

Signal Transduction Lab, Department of Bio-Chemistry, Faculty of Biological Sciences, Quaid-i-Azam University Islamabad, Islamabad, Pakistan.

Data is about the mitochondrial apoptosis regulatory framework genes PUMA, DRP1 (apoptotic), and ARC (anti-apoptotic) analysis after the employment of their controlling miRNAs inhibitors. The data represents putative conserved targeting of seed regions of miR-15a, miR-29a, and miR-214 with respective target genes PUMA, DRP1, and ARC. Data is of cross interference in expression levels of one miRNA family, miR-29a and its putative target DRP1 upon the inhibitory treatment of other miRNAs 15a and 214.
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http://dx.doi.org/10.1016/j.dib.2017.12.040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5752092PMC
February 2018

Absence of SNCA polymorphisms in Pakistani Parkinsons disease patients.

J Pak Med Assoc 2017 Oct;67(10):1512-1516

Institute of Biomedical and Genetic Engineering (IBGE), Islamabad.

Objective: To elucidate the genetic risk and role of alpha-synuclein gene in the pathogenesis of Parkinson's disease in Pakistani population.

Methods: This case-control study was conducted at Institute of Biomedical and Genetic Engineering (IBGE), Islamabad from May 2013 to May 2016, and comprised patients with Parkinson's disease and their ethnically-matched healthy controls. Allele-specific polymerase chain reaction was used for screening of three pathogenic single nucleotide polymorphisms in alpha-synuclein gene. Moreover, 20% samples were randomly selected for bidirectional Sanger sequencing to confirm the results. SPSS 13 was used for data analysis.

Results: Of the 374 participants, 174(46.5%) were patients and 200(53.5%) were controls. The mean age for the onset of the disease was 55±13 years. No polymorphism was observed for rs104893875(G>A), rs104893877(G>A) and rs104893878(C>G) in alpha-synuclein gene in samples of patients and controls.

Conclusions: Alpha-synuclein gene mutations might not be relevant to all the populations in causing Parkinson's disease.
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October 2017

Interplay of mitochondria apoptosis regulatory factors and microRNAs in valvular heart disease.

Arch Biochem Biophys 2017 11 6;633:50-57. Epub 2017 Sep 6.

Signal Transduction Lab, Department of Bio-Chemistry, Faculty of Biological Sciences, Quaid-i-Azam University Islamabad, Pakistan. Electronic address:

Valvular heart disease (VHD) is an active process involving a wide range of pathological changes. The major complications of VHD are stenosis and regurgitation, which are macroscopic phenomena, induced in part through cellular changes. Altered expression of mitochondria associated genes causes membrane potential depolarization, leading to the increased levels of apoptosis observed in cardiac dysfunction. Objective of this study is to find molecular medicine candidates that can control expression of the key mitochondria apoptosis regulatory genes. Present study aims to assess the way microRNA are involved in regulating mitochondrial apoptosis regulatory genes and observation of their expression in the heart valve dysfunction. Apoptotic genes PUMA and DRP1 were found to be highly expressed, whereas anti-apoptotic gene ARC was down regulated. The expression level of GATA-4 transcription factor was also reduced in cardiac valve tissues. MicroRNAs miR-15a and miR-29a were repressed, while miR-214 was up regulated. Furthermore, study showed that PUMA, DRP1 and ARC expression might be attenuated by their respective miRNAs. Our results indicate that mitochondria regulatory genes might be controlled by miR-15a, miR-29a and miR-214, in VHD patients. Present study may provide platform for future research regarding potential therapeutic role of miRNAs in CVDs.
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http://dx.doi.org/10.1016/j.abb.2017.09.001DOI Listing
November 2017

Further evidence for the association of CYP2D6*4 gene polymorphism with Parkinson's disease: a case control study.

Genes Environ 2017 1;39:18. Epub 2017 Jul 1.

Synaptic Signalling and Neurodegeneration, German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.

Background: Genetic and environmental risk factors play an important role for the susceptibility to sporadic Parkinson's disease (PD). It was hypothesized that a splice variant of the gene ( allele) is associated with PD because it alters the ability to metabolize toxins and in particular neurotoxins. codes for the drug metabolizing enzyme debrisoquine 4-hydroxylase. The CYP2D6*4 variant results in an undetectable enzyme activity and consequently in a reduction in metabolism of some toxins.

Methods: Some of agricultural chemicals have neurotoxic potential and CYP2D6 is involved in their detoxification. Thus, we conducted a case control study to investigate the association of the CYP2D6*4 with PD in a Pakistani subpopulation that is known to be exposed to high levels of some agricultural pesticides, insecticides and herbicides.

Results: We found a significantly higher allele and genotype frequency of the variant in 174 sporadic PD patients when compared to 200 controls. In addition, there was a trend to an earlier age of PD onset and a tremor dominant phenotype in variant carriers.

Conclusion: Our data provide further evidence that a poor metabolizer status may increase the risk to develop PD especially in populations that are exposed to environmental toxins.
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http://dx.doi.org/10.1186/s41021-017-0078-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5493842PMC
July 2017

A report of whole-genome sequencing in neurologic Wilson's disease.

Neurol India 2017 May-Jun;65(3):629-631

Synaptic Signaling and Neurodegeneration, German Cancer Research Center, Heidelberg; Synaptic Signaling and Neurodegeneration, German Center for Neurodegenerative Diseases, Bonn; Institute of Pathophysiology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.

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http://dx.doi.org/10.4103/neuroindia.NI_1274_16DOI Listing
July 2019

Can IFNL3 polymorphisms predict response to interferon/ribavirin treatment in hepatitis C patients with genotype 3?

J Gen Virol 2016 10 5;97(10):2592-2598. Epub 2016 Aug 5.

Institute of Biomedical Genetic Engineering (IBGE), 24 Mauve Area, G-9/1, Islamabad, Pakistan.

Favourable genotypes of IFNL3 polymorphism CC for rs12979860 and TT for rs8099917 are strongly associated with the interferon/ribavirin treatment outcome in hepatitis C virus (HCV) patients with genotypes 1 and 4. Contrarily, conflicting results have been reported for patients with HCV genotypes 2 and 3. Therefore, we sought to investigate the association between IFNL3 with sustained virological response (SVR) after treatment to ascertain the predictive value of IFNL3 single-nucleotide polymorphisms (SNPs) in HCV patients with genotype 3. For this purpose, we genotyped five IFNL3 SNPs, rs12980275, rs12979860, rs9109886, rs8099917 and rs7248668, in HCV patients with genotype 3 and assessed its association with SVR, individually and in haplotype. Interestingly, we report that the IFNL3 SNPs we genotyped have shown no association with SVR following treatment, either individually or in haplotype, indicating that genotyping IFNL3 SNPs have limited predictive value in HCV patients with genotype 3. Therefore, we propose that IFNL3 genotyping can be excluded from a patient's pre-treatment workup for subsequent treatment choice. This will greatly reduce the economic burden for HCV patients with genotype 3 in resource-limited regions, especially South Asia where genotype 3 is predominant.
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http://dx.doi.org/10.1099/jgv.0.000572DOI Listing
October 2016

Extracellular vesicles in ovarian cancer: applications to tumor biology, immunotherapy and biomarker discovery.

Expert Rev Proteomics 2016 ;13(4):395-409

h Princess Margaret Cancer Centre and Department of Medical Biophysics , University of Toronto , Toronto , ON , Canada.

In recent years there has been tremendous interest in both the basic biology and applications of extracellular vesicles (EVs) in translational cancer research. This includes a better understanding of their biogenesis and mechanisms of selective cargo packaging, their precise roles in horizontal communication, and their application as non-invasive biomarkers. The rapid advances in next-generation omics technologies are the driving forces for these discoveries. In this review, the authors focus on recent results of EV research in ovarian cancer. A deeper understanding of ovarian cancer-derived EVs, the types of cargo molecules and their biological roles in cancer growth, metastases and drug resistance, could have significant impact on the discovery of novel biomarkers and innovative therapeutics. Insights into the role of EVs in immune regulation could lead to novel approaches built on EV-based immunotherapy.
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http://dx.doi.org/10.1586/14789450.2016.1165613DOI Listing
December 2016

Clinical role of HER2 gene amplification and chromosome 17: a study on 154 IHC-equivocal cases of invasive breast carcinoma patients.

Tumour Biol 2016 Jul 6;37(7):8665-72. Epub 2016 Jan 6.

Department of Biochemistry, Quaid-i-Azam University, Islamabad, 45320, Pakistan.

Accurate evaluation of human epidermal growth factor receptor 2 (HER2) status is quite crucial for invasive breast tumor patients in order to select anti-HER2 therapy for effective clinical outcomes. Immunohistochemistry (IHC) assay is routinely used to evaluate the HER2 oncoprotein overexpression but is unable to explain the chromosomal and genetic alterations and has been considered as a hot issue in IHC-equivocal cases. We investigated these molecular aberrations in correlation with prognostic factors. A cohort of 154 IHC-equivocal (+2) cases was selected and retrospectively analyzed by dual-probe fluorescence in situ hybridization (FISH) assay by using locus-specific HER2 and centromere enumeration probes (CEP17) for the identification of HER2 proto-oncogene amplification and chromosomal copy number per cell, respectively. The data were analyzed by SPSS 16.0 version using chi-square test (p < 0.05). We identified 36 out of 154 cases (23.4 %) showing HER2 gene amplification (average HER2 gene copies per cell >4 or <4 with HER2/CEP17 ratio >2) in concordance with HER2 oncoprotein overexpression, and significant correlation was observed with prognostic parameters including histological type, tumor grade II to III, histology and pathological type, lymphatic invasion, ductal carcinoma in situ (DCIS), and estrogen-positive and progesterone-negative receptors. Of the 154 cases, 18 cases (11.7 %) showed polysomy 17 with CEP17 probe signals per cell ≥3 and 22 cases (14.3 %) presented monosomy 17 (CEP17 probe signals per cell ≤1). Our data indicate that the use of anti-HER2 therapy should not be suggested unless true evaluation of HER2 protein expression is made regarding gene amplification essentially in IHC-ambiguous invasive breast tumors.
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http://dx.doi.org/10.1007/s13277-015-4657-7DOI Listing
July 2016

The erratic antibiotic susceptibility patterns of bacterial pathogens causing urinary tract infections.

EXCLI J 2015 4;14:916-25. Epub 2015 Aug 4.

Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan ; Institute of Health and Management Sciences, Shaheed Zulfiqar Ali Bhutto Medical University, Islamabad, Pakistan.

Increasing trend of antibiotic resistance and expression of Extended Spectrum Beta Lactamases (ESBLs) are serious threats for public health as they render the treatment ineffective. Present study was designed to elucidate the antibiotic-susceptibility patterns of ESBL and non-ESBL producing E. coli and K. pneumoniae causing urinary tract infections so that the ineffective antibiotics could be removed from the line of treatment. The bacterial isolates obtained from the urine of patients visiting a tertiary health care facility were cultured for strain identification using API20E. Antimicrobial susceptibility and ESBL detection were done by Kirby-bauer diffusion technique. Almost 53.4 % isolates of E. coli and 24.5 % isolates of K. pneumoniae were found to be ESBL producers. The ESBL producing bacteria were found to be more resistant towards various antibiotics. The most effective drugs against E. coli ESBL isolates were imipenem (99.54 %), ampicillin-sulbactam (97.48 %), piperacillin-tazobactam (96.86 %), fosfomycin (94.51 %), amikacin (92.26 %) and nitrofurantoin (90.68 %). The most effective drugs against K. pneumoniae ESBL isolates were imipenem (97.62 %), piperacillin-tazobactam (95.35 %), ampicillin-sulbactam (90.48 %) and amikacin (88.37 %). The antibiotics having the highest resistance, particularly by the ESBL producers were amoxicillin clavulanic acid, sulphamethoxalzole/ trimethoprim, cefuroxime, cefpirome, ceftriaxone and ciprofloxacin. Most of the isolates showed multi drug resistance (MDR). High frequency of ESBL producing E. coli and K. pneumoniae were observed as compared to previous data. Penicillins, cephalosporins and some representatives of fluoroquinolones were least effective against the common UTIs and are recommended to be removed from the line of treatment.
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http://dx.doi.org/10.17179/excli2015-207DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4669912PMC
December 2015

Transcriptional up-regulation of BMP-4 and BMPR-II genes in the peripheral blood of breast cancer patients: A pilot study.

Cancer Biomark 2015 ;15(5):551-7

Nuclear Medicine of Oncology and Radiotherapy Institute (NORI), Islamabad, Pakistan.

Background: Bone morphogenetic proteins (BMPs) belong to the transforming growth factor beta (TGF-β) super family, which are primarily known for their inherent role in osteogenesis and ontogenesis. Accumulating evidence suggests the regulatory role of BMP-4 in cellular proliferation, apoptosis, differentiation and thus a possible oncogenic role.

Objective: Variable cellular expression and in vitro functional assays are indicative of the involvement of BMP related signaling in Breast cancer (BC). The differential expression of BMP-4 in the peripheral blood of BC patients may therefore be considered as a potential biomarker. Therefore, this study aimed to evaluate transcriptional expression of BMP-4 and its cognate receptor BMPR-II in the peripheral blood from the BC patients in relation to the healthy individuals.

Methods: The expression pattern of BMP-4 and BMPR-II was analyzed in the blood of breast cancer patients (n = 22) and healthy controls (n = 22) through Semi Quantitative Reverse transcription Polymerase chain reaction.

Results: An up-regulated expression of BMP-4 and BMPR-II was observed in the peripheral blood of breast cancer patients especially in the advanced-stage of the disease. Moreover, BMP-4 and BMPR-II expressions were found to be correlated.

Conclusion: The current preliminary results based on the transcriptional analysis suggest the prospective use of BMP4 as a biomarker, however further validation is required.
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http://dx.doi.org/10.3233/CBM-150494DOI Listing
July 2016

Knowledge and awareness about breast cancer and its early symptoms among medical and non-medical students of Southern Punjab, Pakistan.

Asian Pac J Cancer Prev 2015 ;16(3):979-84

Atta-ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, Islamabad, Pakistan E-mail :

Breast cancer is the leading cause of morbidity and mortality globally but has an even more significant impact in developing countries. Pakistan has the highest prevalence among Asian countries. A general lack of public awareness regarding the disease often results in late diagnosis and poor treatment outcomes. The literacy rate of the Southern Punjab (Pakistan) is low compared to its Northern part. It is therefore vital that university students and especially medical students develop a sound knowledge about the disease so that they can spread awareness to others who may be less educated. This study therefore considers current knowledge and understanding about the early signs of breast cancer amongst a study group of medical and non-medical university students of the Southern Punjab, Pakistan. A cross-sectional descriptive analysis of the university students was carried out using a self-administered questionnaire to assess their awareness of breast cancer from March to May 2014. A total of 566 students participated in this study, out of which 326 were non-medical and 240 were from a medical discipline. Statistical analysis was carried out using Graph Pad Prism Version 5 with a significance level set at p<0.05. The mean age of the non medical and medical participants was 23 (SD 2.1) and 22 (SD 1.3) years, respectively. Less than 35% students were aware of the early warning signs of the breast cancer development. Knowledge of medical students about risk factors was significantly better than the non medical ones, but on the whole was insufficient. Our study indicated that knowledge regarding breast cancer was generally insufficient amongst the majority of the university students (75% non-medical and 55% medical) of Southern Punjab, Pakistan. This study highlights the need to formulate an awareness campaign and to organize conferences to promote breast cancer awareness among students in this region.
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http://dx.doi.org/10.7314/apjcp.2015.16.3.979DOI Listing
December 2015

Effect of maternal iodine supplementation on thyroid function and birth outcome in goiter endemic areas.

Curr Med Res Opin 2015 Apr 13;31(4):667-74. Epub 2015 Feb 13.

Department of Biochemistry, Quaid-i-Azam University , Islamabad , Pakistan.

Objective: The study was undertaken to examine the clinical and endocrine parameters of thyroid in a total of 460 pregnant women belonging to non-goiter areas (group 1; n = 156) and endemic areas without (group 2; n = 154) and with iodine supplementation (group 3; n = 150), and their respective newborns.

Methods: Women of group 3 with visible goiter were administered two capsules of iodized oil orally each containing 200 mg of iodine, from weeks 6--8 of pregnancy. Blood samples were obtained from all groups during each trimester, at parturition (umbilical cord blood) and after delivery. Serum triiodothyronine (T3), thyroxine (T4) and thyroid stimulating hormone (TSH) levels were measured by specific enzyme immunoassays.

Results: In group 2, serum T4 concentrations were low while T3 and TSH levels were high which showed hypothyroidism in the women of endemic areas. Goiter size decreased in most of the subjects who received a single dose of iodized oil and resulted in increase in serum concentrations of thyroid hormones; whereas, TSH levels decreased. Iodine supplementation also resulted in raised T4 and low TSH levels in the cord blood of neonates. During the course of study, two abortions, three still births and one cretin were reported in group 2; none was reported in group 3; and one still birth was reported in group 1.

Conclusions: The oral administration of a single dose of iodized oil is capable of correcting iodine deficiency both clinically and endocrinologically in mothers and neonates. Iodine supplementation has the potential to positively impact the birth weight of newborns.
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http://dx.doi.org/10.1185/03007995.2015.1011779DOI Listing
April 2015

The transcriptional repressor ZEB1 promotes metastasis and loss of cell polarity in cancer.

Cancer Res 2008 Jan;68(2):537-44

Department of Visceral Surgery, University of Freiburg, Freiburg, Germany.

Invasion and metastasis are the hallmarks of malignant tumor progression and the main cause of death in cancer. The embryonic program "epithelial-mesenchymal transition" (EMT) is thought to trigger invasion by allowing tumor cell dissemination. Here, we describe that the EMT-inducing transcriptional repressor ZEB1 promotes colorectal cancer cell metastasis and loss of cell polarity. Thereby, ZEB1 suppresses the expression of cell polarity factors, in particular of Lgl2, which we found reduced in colorectal and breast cancers. We further show that retention of Lgl2 expression is critical for the epithelial phenotype and that its loss might be involved in metastasis. Thus, by linking EMT, loss of polarity, and metastasis, ZEB1 is a crucial promoter of malignant tumor progression.
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http://dx.doi.org/10.1158/0008-5472.CAN-07-5682DOI Listing
January 2008

The transcription factor ZEB1 (deltaEF1) represses Plakophilin 3 during human cancer progression.

FEBS Lett 2007 Apr 21;581(8):1617-24. Epub 2007 Mar 21.

Max F. Perutz Laboratories, Department of Medical Biochemistry, Medical University Vienna, Dr. Bohrgasse 9, A-1030 Vienna, Austria.

Plakophilin 3 (PKP3) belongs to the p120ctn family of armadillo-related proteins predominantly functioning in desmosome formation. Here we report that PKP3 is transcriptionally repressed by the E-cadherin repressor ZEB1 in metastatic cancer cells. ZEB1 physically associates with two conserved E-box elements in the PKP3 promoter and partially represses the activity of corresponding human and mouse PKP3 promoter fragments in reporter gene assays. In human tumours ZEB1 is upregulated in invasive cancer cells at the tumour-host interface, which is accompanied by downregulation of PKP3 expression levels. Hence, the transcriptional repression of PKP3 by ZEB1 contributes to ZEB1-mediated disintegration of intercellular adhesion and epithelial to mesenchymal transition.
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http://dx.doi.org/10.1016/j.febslet.2007.03.026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2938730PMC
April 2007