89 results on '"Kaiser Jamil"'
Search Results
2. Identification of novel allosteric binding sites and multi-targeted allosteric inhibitors of receptor and non-receptor tyrosine kinases using a computational approach
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Kaiser Jamil and Kavita Kumari Kakarala
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Binding Sites ,Lung Neoplasms ,biology ,Drug discovery ,Chemistry ,Allosteric regulation ,Fusion Proteins, bcr-abl ,Druggability ,General Medicine ,Computational biology ,Receptor tyrosine kinase ,Drug repositioning ,Allosteric Regulation ,Structural Biology ,Docking (molecular) ,Carcinoma, Non-Small-Cell Lung ,biology.protein ,Humans ,Tyrosine ,Protein Kinase Inhibitors ,Molecular Biology ,Tyrosine kinase ,Allosteric Site ,Proto-oncogene tyrosine-protein kinase Src - Abstract
EGFR1, VEGFR2, Bcr-Abl and Src kinases are key drug targets in non-small cell lung cancer (NSCLC), bladder cancer, pancreatic cancer, CML, ALL, colorectal cancer, etc. The available drugs targeting these kinases have limited therapeutic efficacy due to novel mutations resulting in drug resistance and toxicity, as they target ATP binding site. Allosteric drugs have shown promising results in overcoming drug resistance, but the discovery of allosteric drugs is challenging. The allosteric binding pockets are difficult to predict, as they are generally associated with high energy conformations and regulate protein function in yet unknown mechanisms. In addition, the discovery of drugs using conventional methods takes long time and goes through several challenges, putting the lives of many cancer patients at risk. Therefore, the aim of the present work was to apply the most successful, drug repurposing approach in combination with computational methods to identify kinase inhibitors targeting novel allosteric sites on protein structure and assess their potential multi-kinase binding affinity. Multiple crystal structures belonging to EGFR1, VEGFR2, Bcr-Abl and Src tyrosine kinases were selected, including mutated, inhibitor bound and allosteric conformations to identify potential leads, close to physiological conditions. Interestingly the potential inhibitors identified were peptides. The drugs identified in this study could be used in therapy as a single multi-kinase inhibitor or in a combination of single kinase inhibitors after experimental validation. In addition, we have also identified new hot spots that are likely to be druggable allosteric sites for drug discovery of kinase-specific drugs in the future.Communicated by Ramaswamy H. Sarma.
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- 2021
3. Azadirachta indica based biosynthesis of silver nanoparticles and evaluation of their antibacterial and cytotoxic effects
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Mohammed Rafi Shaik, M. Asimuddin, Kaiser Jamil, Abdulrahman Al-Warthan, Mujeeb Khan, Mohammed Rafiq H. Siddiqui, and Syed Farooq Adil
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Multidisciplinary ,Aqueous solution ,biology ,02 engineering and technology ,010501 environmental sciences ,Azadirachta ,021001 nanoscience & nanotechnology ,biology.organism_classification ,01 natural sciences ,Silver nanoparticle ,Minimum inhibitory concentration ,Silver nitrate ,chemistry.chemical_compound ,chemistry ,MTT assay ,Surface plasmon resonance ,0210 nano-technology ,Antibacterial activity ,lcsh:Science (General) ,0105 earth and related environmental sciences ,Nuclear chemistry ,lcsh:Q1-390 - Abstract
Due to the growing threat to the environment by the climate change, the development of sustainable and environmental friendly methods for the preparation of metallic nanoparticles (NPs) is highly desirable. Herein, we demonstrate a simple and eco-friendly method for the preparation of silver nanoparticles (AgNPs) using Azadirachta indica leaf extract and aqueous solution of silver nitrate (AgNO3). The effect of concentration of leaf extract and temperature on the synthesis of AgNPs is studied. It was revealed that 1 mM of AgNO3, leaf extract concentration of 60 mg/mL, 30 min of reaction time and a temperature 85 °C were found to be optimum for the synthesis good quality AgNPs. The formation of AgNPs was confirmed by UV–Vis analysis, where the UV spectrum exhibited a highest absorption peak at ∼410 nm corresponding to the surface Plasmon Resonance (SPR) of the AgNPs. Furthermore, the antibacterial activity of biosynthesised AgNPs was investigated and the inhibitory concentrations of 0.5 µg/mL for Escherichia coli and 1.0 µg/mL for Staphylococcus aureus were found. Besides, the in vitro cytotoxicity investigation of biosynthesized AgNPs against human acute lymphoblastic leukemia cells via MTT assay showed that the minimum inhibitory concentration of 15.6 µg/mL was required. Therefore, the eco-friendly and cost effective synthesis of AgNPs has potential for biomedical applications and this method can be used for the large scale production of AgNPs. Keywords: Azadirachta indica, AgNPs, Biosynthesis, Antimicrobial activities, Cytotoxicity
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- 2020
4. Polymorphism in EGFR Gene and its Association in Head and Neck Cancer Patients with Tobacco and Alcohol Consuming Habits
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K. Nagalakshmi, Kaiser Jamil, and P. Usha Rani
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Oncology ,medicine.medical_specialty ,biology ,business.industry ,Head and neck cancer ,Single-nucleotide polymorphism ,Single-strand conformation polymorphism ,medicine.disease ,Polymorphism (computer science) ,Internal medicine ,Genotype ,medicine ,biology.protein ,SNP ,Gene polymorphism ,Epidermal growth factor receptor ,business - Abstract
Single nucleotide polymorphism (SNP) in the epidermal growth factor receptor (EGFR) plays a crucial role in head and neck cancer (HNC) disease progression and targeted therapies. Hence the present study aims to identify the mutations in EGFR gene (exon 20) in HNC considering their exposure to tobacco and alcohol habits. Mutational analysis was carried out by polymerase chain reaction (PCR) followed by single stranded confirmatory polymorphism (SSCP) techniques on the study group comprising of 129 HNC cases and 150 healthy volunteers. Four different SNP’s (R776H, G779G, Q787Q, and L798H) were observed with the overall mutation rate of 75.19% in HNC cases and 46% in controls. Q787Q was found to be more prevalent (p,0.05) and its genotypes GG, GA, and AA were 24.80%, 61.24%, and 13.95%. The study concluded that EGFR was found to be a polymorphic gene associated with HNC disease, and these SNPs were also prevalent in healthy volunteers with tobacco and alcohol habits. The observed SNPs in healthy volunteers indicated the importance of relative risk to HNC disease. These mutations were known to increase growth factor signaling cascade and confer susceptibility to the inhibitors.
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- 2021
5. Role of cytochrome epoxygenase (CYP2J2) in the pathophysiology of coronary artery disease in South Indian population
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Javeed Ahmad Tantray, Kaiser Jamil, K. Pratap Reddy, and Shiva Kumar Yerra
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Adult ,Male ,Epoxygenase ,medicine.medical_specialty ,RD1-811 ,Genotype ,Homocysteine ,India ,Coronary Artery Disease ,030204 cardiovascular system & hematology ,Real-Time Polymerase Chain Reaction ,Cytochrome P-450 CYP2J2 ,CYP2J2 ,Coronary artery disease ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Cytochrome P-450 Enzyme System ,Risk Factors ,Internal medicine ,medicine ,Diseases of the circulatory (Cardiovascular) system ,Humans ,Genetic Predisposition to Disease ,Genetic Testing ,030212 general & internal medicine ,Letter to the Editor ,Genotyping ,Retrospective Studies ,Creatinine ,biology ,Cholesterol ,business.industry ,Incidence ,DNA ,Middle Aged ,medicine.disease ,Endocrinology ,Gene Expression Regulation ,chemistry ,RC666-701 ,biology.protein ,Surgery ,Female ,lipids (amino acids, peptides, and proteins) ,Cardiology and Cardiovascular Medicine ,business ,Follow-Up Studies ,Lipoprotein - Abstract
Background: The cytochrome P-450 2J2 (CYP2J2) is known to be one of the major enzymes of epoxygenase pathway of arachidonic acid in extrahepatic tissues, which produces series of regioisomeric cis-epoxyeicosatrienoic acids (EETs) such as 5,6-, 8,9-, 11,12-, and 14,15-EETs. In the present study, we analyzed the impact of a genetic variant in CYP2J2 on coronary artery disease (CAD) in the Telangana region of Indian population. Material and methods: The case–control study consisted of 100 CAD cases and 110 healthy controls. The deoxyribonucleic acid was extracted using the salting out method. Genotyping and gene expression was performed by polymerase chain reaction (PCR)-restriction fragment length polymorphism and real-time-PCR methods. Results: In the present study, the percentage of smokers, alcoholics, hypertensive patients, and diabetics was high. Increase in fasting glucose, urea, creatinine, fasting triglycerides, total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), total cholesterol/high-density lipoprotein (TC/HDL), LDL/HDL, homocysteine, and C-reactive protein levels were significantly higher in patients with CAD than in controls (p
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- 2019
6. Analysis of CCND1 protein and circulatory antioxidant enzyme activity association in oral squamous cell carcinoma
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Bader Homoud Alali, P. Udaykumar, Ayesha Mateen, Rabbani Syed, Shatha A. Alduraywish, Kaiser Jamil, P.S. Sushma, and Fahad M. Aldakheel
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Antioxidant ,QH301-705.5 ,medicine.medical_treatment ,Pharmacology ,Antioxidants ,Cyclin D1 ,medicine ,Basal cell ,Biology (General) ,chemistry.chemical_classification ,biology ,business.industry ,Smoking ,Cancer ,medicine.disease ,Enzyme assay ,CCND1 Protein ,Enzyme ,chemistry ,Catalase ,Circulatory system ,biology.protein ,Original Article ,OSCC ,General Agricultural and Biological Sciences ,business - Abstract
Antioxidants are involved in the process of cellular damage prevention, which is considered as an avenue for cancer development. Free radicals are produced in the body upon exposure to stress, cigarette smoke, alcohol, toxins found in personal care products, pesticides in foods, radiation from the sun, viruses, germs or fungi etc. CCND1/CyclinD1 protein was found to be overexpressed in Oral squamous cell carcinoma. One hundred patients with oral squamous cell carcinoma were recruited along with hundred controls for this study from MNJ institute of Oncology with the approval of Ethics Committee, 5 ml blood samples were collected from each patient and centrifuged to collect serum for various assays. The antioxidant enzymes like catalase, SOD, GPX and GST were estimated using enzymatic assays. Results were expressed as unit of activity for mg of protein. Insilco analysis is performed using STRING v 11 Protein interaction tool. The patients with oral cancer had significantly reduced activities of SOD, GST and GPX (1.49 ± 0.49, 3.97 ± 0.86 and 10.7 ± 0.73 respectively) compared to healthy controls (4.37 ± 1.43, 6.10 ± 1.12 and 13.8 ± 1.25 respectively) (p
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- 2021
7. Study of Antibacterial Properties of Ziziphus mauritiana based Green Synthesized Silver Nanoparticles against Various Bacterial Strains
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M. Asimuddin, Mohammed Rafiq H. Siddiqui, Neeshat Fathima, Syed Farooq Adil, Mohammed Rafi Shaik, Mujeeb Khan, Kaiser Jamil, and M. Shaistha Afreen
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plant extracts ,Geography, Planning and Development ,Flavonoid ,Nanoparticle ,TJ807-830 ,biological activity ,02 engineering and technology ,Management, Monitoring, Policy and Law ,medicine.disease_cause ,TD194-195 ,01 natural sciences ,Silver nanoparticle ,Renewable energy sources ,chemistry.chemical_compound ,Minimum inhibitory concentration ,medicine ,GE1-350 ,ziziphus mauritiana ,Escherichia coli ,chemistry.chemical_classification ,Aqueous solution ,biology ,Environmental effects of industries and plants ,010405 organic chemistry ,Renewable Energy, Sustainability and the Environment ,green synthesis ,Ziziphus ,021001 nanoscience & nanotechnology ,biology.organism_classification ,0104 chemical sciences ,Environmental sciences ,Silver nitrate ,chemistry ,0210 nano-technology ,silver nps ,Nuclear chemistry - Abstract
Due to their low cost and environmentally friendly nature, plant extracts based methods have gained significant popularity among researchers for the synthesis of metallic nanoparticles. Herein, green synthesis of silver nanoparticles was performed using the aqueous solution of Ziziphus mauritiana leaves extract (ZM-LE) as a bio-reducing agent. The as-obtained silver nanoparticles were characterized by using UV-Vis spectroscopy, XRD (X-ray diffraction), TEM (transmission electron microscopy), and FT-IR (Fourier-transform infrared spectroscopy). In addition, the effects of the concentrations of the leaves extract, silver nitrate, and the temperature on the preparation of nanoparticles were also investigated. In order to determine the nature of secondary metabolites present in leaves extract, a preliminary investigation of phytoconstituents was carried out using different methods including Folin-Ciocalteu and AlCl3 methods. The results have indicated the presence of a considerable amount of phenolic and flavonoid contents in the leaves extract, which are believed to be responsible for the reduction of silver ions and stabilization of resulting nanoparticles. Indeed, the FT-IR spectrum of silver nanoparticles also confirmed the presence of residual phytomolecules of leaves extract as stabilizing ligands on the surface of nanoparticles. The antibacterial properties of as-obtained silver nanoparticles were tested against various bacterial strains including Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, and Bacillus subtilis. The nanoparticles strongly inhibited the growth of S. aureus with a minimum inhibitory concentration (MIC) of 2.5 &mu, g/ml and moderately inhibited the growth of E. coli with a MIC of 5 &mu, g/ml.
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- 2020
8. Molecular insights into the coding region mutations of low-density lipoprotein receptor adaptor protein 1 (LDLRAP1) linked to familial hypercholesterolemia
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Babajan Banaganapalli, Kaiser Jamil, Zuhier Awan, Khalidah Khalid Nasser, Noor Ahmad Shaik, Ramu Elango, Faten Al‐Qahtani, and Nuha Alrayes
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0301 basic medicine ,Models, Molecular ,Genotype ,Mutation, Missense ,Familial hypercholesterolemia ,Biology ,Hyperlipoproteinemia Type II ,03 medical and health sciences ,Open Reading Frames ,Structure-Activity Relationship ,0302 clinical medicine ,Protein structure ,Drug Discovery ,Databases, Genetic ,Genetics ,medicine ,Coding region ,Missense mutation ,Humans ,Genetic Predisposition to Disease ,Molecular Biology ,Genetics (clinical) ,Genetic Association Studies ,Adaptor Proteins, Signal Transducing ,Signal transducing adaptor protein ,Computational Biology ,medicine.disease ,Phenotype ,030104 developmental biology ,Amino Acid Substitution ,ROC Curve ,Docking (molecular) ,030220 oncology & carcinogenesis ,LDL receptor ,Mutation ,Molecular Medicine ,Protein Binding - Abstract
Background Familial hypercholesterolemia (FH) is a lipid disorder caused by pathogenic mutations in LDLRAP1 gene. The present study has aimed to deepen our understanding about the pathogenicity predictions of FH causative genetic mutations, as well as their relationship to phenotype changes in LDLRAP1 protein, by utilizing multidirectional computational analysis. Methods FH linked LDLRAP1 mutations were mined from databases, and the prediction ability of several pathogenicity classifiers against these clinical variants, was assessed through different statistical measures. Furthermore, these mutations were 3D modelled in protein structures to assess their impact on protein phenotype changes. Results Our findings suggest that Polyphen-2, when compared with SIFT, M-CAP and CADD tools, can make better pathogenicity predictions for FH causative LDLRAP1 mutations. Through, 3D simulation and superimposition analysis of LDLRAP1 protein structures, it was found that missense mutations do not create any gross changes in the protein structure, although they could induce subtle structural changes at the level of amino acid residues. Near native molecular dynamic analysis revealed that missense mutations could induce variable degrees of fluctuation differences guiding the protein flexibility. Stability analysis showed that most missense mutations shifts the free energy equilibrium and hence they destabilize the protein. Molecular docking analysis demonstrates the molecular shifts in hydrogen and ionic bonds and Van der waals bonding properties, which further cause differences in the binding energy of LDLR-LDLRAP1 proteins. Conclusions The diverse computational approaches used in the present study may provide a new dimension for exploring the structure-function relationship of the novel and deleterious LDLRAP1 mutations linked to FH.
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- 2019
9. Promoter epigenetics of APC gene and its implication in sporadic breast cancer patients from South Indian population
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Kaiser Jamil, G. Suryanarayana Raju, and Nasrin Begam
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0301 basic medicine ,biology ,Tumor suppressor gene ,Adenomatous polyposis coli ,Cellular differentiation ,Wnt signaling pathway ,Methylation ,medicine.disease_cause ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,030220 oncology & carcinogenesis ,DNA methylation ,Genetics ,biology.protein ,Cancer research ,medicine ,Epigenetics ,Carcinogenesis - Abstract
Background The adenomatous polyposis coli (APC) gene is a tumor suppressor gene associated with both familial and sporadic cancer, whose protein plays an important role in the WNT signal transduction pathway. WNT signaling is a key developmental pathway involved in embryonic development, cell differentiation, cell proliferation and tissue maintenance in adults. APC protein acts as an antagonist of the WNT signaling pathway by binding and regulating the β-catenin protein. Impaired APC gene function usually leads to a lack of degradation of β-catenin, which could cause uncontrolled cell growth and lead to tumorigenic transformation. APC gene may be inactivated by aberrant DNA methylation of CpG islands in their promoter regions. Objective Hence the present study was designed to determine the role of promoter methylation of APC genes in sporadic breast cancer patients from South Indian population. Methods DNA methylation analyses of APC gene was performed by methylation-specific polymerase chain reaction (MSP).·Fifty biopsy samples of breast tumor and their corresponding non-malignant portions as controls were studied comparatively. APC mRNA expression analysis was also done using real time PCR. Results Thirty eight percent (38%) cancerous tissue samples (19/50) showed promoter hypermethylation in APC gene; however, none of normal tissues showed promoter hypermethylation. The difference in methylation frequency between cancerous and normal tissue was statistically significant (p = 0.0001). APC promoter methylation was positively associated with lymph node involvement (p = 0.048), APC Promote hyper methylation and decreased mRNA expression was significantly associated (p = 0.0034). Lower APC-mRNA expression was associated with patient's age above 50 years (p = 0.044). Conclusion In conclusion, our data showed that promoter hypermethylation of APC gene was a prognostic factor in breast cancer patients from South Indian population. The loss of APC gene function usually leads to an accumulation of β-catenin, which may promote tumorigenesis.
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- 2018
10. A Study of C677T Polymorphism of Methylenetetrahydrofolate Reductase (MTHFR) Gene and It’s Susceptibility in Coronary Artery Disease
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Javeed Ahmad Tantray, Karnati Pratap Reddy, Shiva Kumar Yerra, and Kaiser Jamil
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Coronary artery disease ,medicine.medical_specialty ,biology ,business.industry ,Internal medicine ,Methylenetetrahydrofolate reductase ,Materials Chemistry ,medicine ,biology.protein ,Mthfr c677t ,business ,medicine.disease ,Gastroenterology - Published
- 2018
11. TNF-alpha −308G/A and −238G/A polymorphisms and its protein network associated with type 2 diabetes mellitus
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Sindhu Joshi, Javeed Ahmad, Archana Jayaraman, Kaiser Jamil, and Shiva Kumar Yerra
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0301 basic medicine ,Genotypes ,030209 endocrinology & metabolism ,Single-nucleotide polymorphism ,Biology ,Bioinformatics ,Article ,03 medical and health sciences ,0302 clinical medicine ,Insulin resistance ,Diabetes mellitus ,Genotype ,Type 2 diabetes mellitus ,medicine ,Polymorphism ,lcsh:QH301-705.5 ,Agricultural and Biological Sciences(all) ,Type 2 Diabetes Mellitus ,Promoter ,medicine.disease ,Protein interaction network ,030104 developmental biology ,lcsh:Biology (General) ,TNF-α ,Tumor necrosis factor alpha ,General Agricultural and Biological Sciences ,TCF7L2 ,SNPs - Abstract
Several reports document the role of tumor necrosis factor alpha (TNF-α) and lipid metabolism in the context of acute inflammation as a causative factor in obesity-associated insulin resistance and as one of the causative parameter of type 2 diabetes mellitus (T2DM). Our aim was to investigate the association between −308G/A and −238G/A polymorphisms located in the promoter region of the TNF-α gene in T2DM in the Indian population with bioinformatics analysis of TNF-α protein networking with an aim to find new target sites for the treatment of T2DM. Demographics of 100 diabetes patients and 100 healthy volunteers were collected in a structured proforma and 3 ml blood samples were obtained from the study group, after approval of Institutional Ethics Committee of the hospital (IEC). The information on clinical parameters was obtained from medical records. Genomic DNA was extracted; PCR–RFLP was performed using TNF-α primers specific to detect the presence of SNPs. Various bioinformatics tools such as STRING software were used to determine its network with other associated genes. The PCR–RFLP studies showed that among the −238G/A types the GG genotype was 87%, GA genotype was 12% and AA genotype was 1%. Almost a similar pattern of results was obtained with TNF-α −308G/A polymorphism. The results obtained were evaluated statistically to determine the significance. By constructing TNF-α protein interaction network we could analyze ontology and hubness of the network to identify the networking of this gene which may influence the functioning of other genes in promoting T2DM. We could identify new targets in T2DM which may function in association with TNF-α. Through hub analysis of TNF-α protein network we have identified three novel proteins RIPK1, BIRC2 and BIRC3 which may contribute to TNF-mediated T2DM pathogenesis. In conclusion, our study indicated that some of the genotypes of TNF-α −308G/A, −238G/A were not significantly associated to type 2 diabetes mellitus, but TNF-α −308G/A polymorphism was reported to be a potent risk factor for diabetes in higher age (>45) groups. Also, the novel hub proteins may serve as new targets against TNF-α T2DM pathogenesis. Keywords: TNF-α, Type 2 diabetes mellitus, Polymorphism, Genotypes, SNPs, Protein interaction network
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- 2017
12. Estimation of Antibacterial Activity of Plants Extracts from Phyllanthus Emblica, Terminalia Chebula and Eucalyptus Globulus Against Oral Pathogens
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Kaiser Jamil
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0106 biological sciences ,0301 basic medicine ,Terminalia chebula ,03 medical and health sciences ,030104 developmental biology ,biology ,Traditional medicine ,Eucalyptus globulus ,Phyllanthus emblica ,biology.organism_classification ,Antibacterial activity ,01 natural sciences ,010606 plant biology & botany - Published
- 2017
13. PTEN and p16 genes as epigenetic biomarkers in oral squamous cell carcinoma (OSCC): a study on south Indian population
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Kaiser Jamil, M Ramakrishna, Pulivarthi Sushma, U Satyanarayana, P. Uday Kumar, and B Triveni
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Adult ,Male ,0301 basic medicine ,Biopsy ,India ,Models, Biological ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Biomarkers, Tumor ,medicine ,Humans ,PTEN ,Tensin ,Epigenetics ,Promoter Regions, Genetic ,Gene ,Cyclin-Dependent Kinase Inhibitor p16 ,Early Detection of Cancer ,Aged ,Mouth neoplasm ,biology ,Genes, p16 ,PTEN Phosphohydrolase ,Cancer ,DNA, Neoplasm ,General Medicine ,Methylation ,DNA Methylation ,Middle Aged ,medicine.disease ,Gene Expression Regulation, Neoplastic ,Cell Transformation, Neoplastic ,030104 developmental biology ,030220 oncology & carcinogenesis ,DNA methylation ,Carcinoma, Squamous Cell ,biology.protein ,Cancer research ,Female ,Mouth Neoplasms - Abstract
Phosphatase and tensin homolog (PTEN) and p16INK4a (p16) genes are tumor suppressor genes, associated with epigenetic alterations. PTEN and p16 promoter hypermethylation is a major epigenetic silencing mechanism leading to cancer. The cooperation between PTEN and p16 in pathogenesis of cancers suggest that their combination might be considered as potential molecular marker for specific subgroups of patients. Hence, the present study aimed to investigate whether PTEN and p16 promoter methylations were involved in oral squamous cell carcinoma (OSCC) in south Indian subjects. DNA methylation quantitative analyses of the two candidate tumor suppressor genes PTEN and p16 were performed by methylation-specific polymerase chain reaction (MSP). Fifty OSCC biopsy samples and their corresponding non-malignant portions as controls were studied comparatively. The methylation status was correlated with the clinical manifestations. Twelve out of 50 patients (24 %) were found to be methylated for PTEN gene, whereas methylation of the p16 gene occurred in 19 out of 50 cases (38 %). A statistically significant result was obtained (P =
- Published
- 2015
14. Identifying new targets in leukemogenesis using computational approaches
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Kaiser Jamil, Archana Jayaraman, and Haseeb A. Khan
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Prioritization ,Acute Lymphoblastic Leukemia (ALL) ,Microarray ,Agricultural and Biological Sciences(all) ,Microarray analysis techniques ,Lymphoblastic Leukemia ,In silico ,Microarray analysis ,Disease ,Computational biology ,Biology ,Bioinformatics ,Protein interaction network ,Gene prioritization ,Therapeutic targets ,Original Article ,General Agricultural and Biological Sciences ,Gene ,Protein network - Abstract
There is a need to identify novel targets in Acute Lymphoblastic Leukemia (ALL), a hematopoietic cancer affecting children, to improve our understanding of disease biology and that can be used for developing new therapeutics. Hence, the aim of our study was to find new genes as targets using in silico studies; for this we retrieved the top 10% overexpressed genes from Oncomine public domain microarray expression database; 530 overexpressed genes were short-listed from Oncomine database. Then, using prioritization tools such as ENDEAVOUR, DIR and TOPPGene online tools, we found fifty-four genes common to the three prioritization tools which formed our candidate leukemogenic genes for this study. As per the protocol we selected thirty training genes from PubMed. The prioritized and training genes were then used to construct STRING functional association network, which was further analyzed using cytoHubba hub analysis tool to investigate new genes which could form drug targets in leukemia. Analysis of the STRING protein network built from these prioritized and training genes led to identification of two hub genes, SMAD2 and CDK9, which were not implicated in leukemogenesis earlier. Filtering out from several hundred genes in the network we also found MEN1, HDAC1 and LCK genes, which re-emphasized the important role of these genes in leukemogenesis. This is the first report on these five additional signature genes in leukemogenesis. We propose these as new targets for developing novel therapeutics and also as biomarkers in leukemogenesis, which could be important for prognosis and diagnosis.
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- 2015
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15. Decidual expression and localization of human surfactant protein SP-A and SP-D, and complement protein C1q
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Kaiser Jamil, Mahesh Choolani, Jinhua Lu, Uday Kishore, and Shanmuga Priyaa Madhukaran
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Adult ,Stromal cell ,Immunology ,Gene Expression ,Collectin ,chemical and pharmacologic phenomena ,Andrology ,Classical complement pathway ,Pregnancy ,Decidua ,medicine ,Humans ,Vimentin ,Molecular Biology ,Pulmonary Surfactant-Associated Protein A ,biology ,Complement C1q ,Keratin-7 ,Trophoblast ,Pulmonary Surfactant-Associated Protein D ,Immunohistochemistry ,Trophoblasts ,Complement system ,Pregnancy Trimester, First ,medicine.anatomical_structure ,Organ Specificity ,Abortion, Legal ,embryonic structures ,biology.protein ,Female ,Stromal Cells ,Antibody ,Biomarkers ,Immunostaining - Abstract
Surfactant proteins SP-A and SP-D, and complement protein C1q are soluble innate immune pattern recognizing molecules. SP-A, SP-D and C1q have an overall similar structure composed of an N-terminal triple-helical collagen region that is followed by a trimeric globular domain. While SP-A and SP-D belong to the collectin family (collagen containing lectin), C1q is the first recognition subcomponent of the classical pathway of the complement system. Recently, SP-A, SP-D and C1q have been considered to play important roles in early and late pregnancy. However, their expression in early human decidua has not been examined. Here, we investigated whether SP-A, SP-D and C1q are expressed within first trimester decidua in humans and their expression is associated with trophoblasts and decidual stromal cells. Decidual samples from women undergoing elective vaginal termination of pregnancy during first trimester were obtained from 25 subjects. Immunohistochemical studies using anti-human SP-A, anti-human SP-D and anti-human C1q antibodies were performed on decidual tissue sections along with anti-vimentin and cytokeratin-7 antibodies to identify stromal cells and trophoblasts. The expression was also examined by immunostaining and PCR using decidual and stromal cells. C1q expression was significantly higher when compared to SP-A and SP-D in the first trimester human decidua. Double immunostaining revealed that all stromal cells and trophoblasts expressed SP-A, SP-D and C1q, while only few invasive trophoblasts expressed C1q. Thus, expression of SP-A, SP-D and C1q in human decidua during first trimester suggests potential role of SP-A, SP-D and C1q during the early stages of pregnancy including implantation, trophoblast invasion and placental development.
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- 2015
16. Homology modelling and molecular docking of MDR1 with chemotherapeutic agents in non-small cell lung cancer
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Syed Subhani, Kaiser Jamil, and Archana Jayaraman
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ATP Binding Cassette Transporter, Subfamily B ,Lung Neoplasms ,Paclitaxel ,Molecular Sequence Data ,Antineoplastic Agents ,Docetaxel ,Biology ,Pharmacology ,Deoxycytidine ,Carboplatin ,Mice ,chemistry.chemical_compound ,Carcinoma, Non-Small-Cell Lung ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Animals ,Humans ,Amino Acid Sequence ,Lung cancer ,neoplasms ,Cisplatin ,Binding Sites ,General Medicine ,medicine.disease ,Gemcitabine ,Molecular Docking Simulation ,chemistry ,Structural Homology, Protein ,Docking (molecular) ,Thermodynamics ,Taxoids ,Sequence Alignment ,medicine.drug ,Combination drug - Abstract
MDR1, a protein commonly involved in drug transport, has been linked to multi drug resistance and disease progression in cancers such as non-small cell lung cancer. Hence, targeting this protein is essential for improving drug design and preventing adverse drug-drug interactions. The aim of the study was to examine chemotherapeutic drug binding to MDR1 and the interactions therein. We have used Schrodinger suite 2014, to perform homology modelling of human MDR1 based on Mouse MDR1, followed by Induced Fit Docking with Paclitaxel, Docetaxel, Gemcitabine, Carboplatin and Cisplatin drugs. Finally, we evaluated drug binding affinities using Prime/MMGBSA and using these scores we compared the affinities of combination therapies against MDR1. Analysis of the docking results showed Paclitaxel>Docetaxel>Gemcitabine>Carboplatin>Cisplatin as the order of binding affinities, with Paclitaxel having the best docking score. The combination drug binding affinity analysis showed Paclitaxel+Gemcitabine to have the best docking score and hence, efficacy. Through our investigation we have identified the residues Gln 195 and Gln 946 to be more frequently involved in drug binding interactions with MDR1. Our results suggest that, Paclitaxel or combination of Paclitaxel+Gemcitabine could serve as a suitable therapy against MDR1 in NSCLC patients. Thus, our study provides new insight into the possible repurposing of chemotherapeutic drugs in targeting elevated MDR1 levels in NSCLC patients, thereby ensuring better overall outcome. Further our study highlights the use of in silico methodologies in understanding drug binding to protein targets and its relevance to advancing lung cancer therapy.
- Published
- 2015
17. Screening of phytochemicals against protease activated receptor 1 (PAR1), a promising target for cancer
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Kaiser Jamil and Kavita Kumari Kakarala
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Virtual screening ,Low toxicity ,Phytochemicals ,Antagonist ,Cell Biology ,Drug resistance ,Pharmacology ,Biology ,medicine.disease ,Biochemistry ,Metastasis ,Molecular Docking Simulation ,Protease-Activated Receptor 1 ,Docking (molecular) ,Catalytic Domain ,Neoplasms ,Toxicity ,medicine ,Humans ,Receptor, PAR-1 ,Molecular Biology ,Protein Binding - Abstract
Drug resistance and drug-associated toxicity are the primary causes for withdrawal of many drugs, although patient recovery is satisfactory in many instances. Interestingly, the use of phytochemicals in the treatment of cancer as an alternative to synthetic drugs comes with a host of advantages; minimum side effects, good human absorption and low toxicity to normal cells. Protease activated receptor 1 (PAR1) has been established as a promising target in many diseases including various cancers. Strong evidences suggest its role in metastasis also.There are no natural compounds known to inhibit its activity, so we aimed to identify phytochemicals with antagonist activity against PAR1.We screened phytochemicals from Naturally Occurring Plant-based Anticancer Compound-Activity-Target database (NPACT, http://crdd.osdd.net/raghava/npact/ ) against PAR1 using virtual screening workflow of Schrödinger software. It analyzes pharmaceutically relevant properties using Qikprop and calculates binding energy using Glide at three accuracy levels (high-throughput virtual screening, standard precision and extra precision).Our study led to the identification of phytochemicals, which showed interaction with at least one experimentally determined active site residue of PAR1, showed no violations to Lipinski's rule of five along with predicted high human absorption. Furthermore, structural interaction fingerprint analysis indicated that the residues H255, D256, E260, S344, V257, L258, L262, Y337 and S344 may play an important role in the hydrogen bond interactions of the phytochemicals screened. Of these residues, H255 and L258 residues were experimentally proved to be important for antagonist binding. The residues Y183, L237, L258, L262, F271, L332, L333, Y337, L340, A349, Y350, A352, and Y353 showed maximum hydrophobic interactions with the phytochemicals screened. The results of this work suggest that phytochemicals Reissantins D, 24,25-dihydro-27-desoxywithaferin A, Isoguaiacin, 20-hydroxy-12-deoxyphorbol angelate, etc. could be potential antagonist of PAR1. However, further experimental studies are necessary to validate their antagonistic activity against PAR1.
- Published
- 2014
18. Polymorphism of CYP3A4*2 and eNOS genes in the diabetic patients with hyperlipidemia undergoing statin treatment
- Author
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Vidya Kandula, M. Asimuddin, Ramoji Kandula, Shiva Kumar Yerra, Kaiser Jamil, and Sindu Joshi
- Subjects
Adult ,Blood Glucose ,Male ,medicine.medical_specialty ,Statin ,Genotype ,Nitric Oxide Synthase Type III ,medicine.drug_class ,Hyperlipidemias ,Type 2 diabetes ,Pharmacology ,Polymorphism, Single Nucleotide ,Young Adult ,chemistry.chemical_compound ,Sex Factors ,Insulin resistance ,Gene Frequency ,Enos ,Internal medicine ,Diabetes mellitus ,Hyperlipidemia ,Genetics ,medicine ,Cytochrome P-450 CYP3A ,Humans ,Molecular Biology ,Genetic Association Studies ,Aged ,biology ,Cholesterol ,business.industry ,Age Factors ,Beclomethasone ,Case-control study ,nutritional and metabolic diseases ,General Medicine ,Middle Aged ,biology.organism_classification ,medicine.disease ,Lipids ,Endocrinology ,Diabetes Mellitus, Type 2 ,chemistry ,Case-Control Studies ,Female ,lipids (amino acids, peptides, and proteins) ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,business - Abstract
In individuals with diabetes, a log linear relationship exists between cholesterol levels and cardiovascular disease. Type 2 diabetes (T2D) and Statins, a cholesterol lowering drug, have a complex relationship. Statins are potent modulators of CYP3A4 2 enzyme and endothelial nitric oxide synthase (eNOS) functions in a number of cholesterol-independent, cardio protective actions in T2D. The aim of this study was to evaluate the CYP3A4 2 and eNOS gene mutations in a large number of T2D patients undergoing statin treatments. Blood samples were collected from 386 subjects in which 196 diabetic patients with hyperlipidemia were undergoing statin treatment (108 females and 88 males). The 190 healthy non-diabetic volunteers formed the control group. We investigated single nucleotide polymorphisms in diabetic patients and controls, and found that the statin therapy was not found to be effective in lowering LDL-cholesterol levels. Statistical analysis showed that T2D patients had significantly higher values of not only glucose levels but also a very high value of Triglycerides and cholesterol at the time of presentation. Our results for CYP3A4 2 showed that the genotype TT (wild type) had lower LDL when compared to TC (heterozygous). Similarly, the genotype TC (heterozygous) had lower LDL when compared to CC (homozygous). A similar trend was observed in the GG (wild type) and GT (heterozygous) of eNOS. In conclusion, we have described for the first time a significant correlation of statin treatment and CYP3A4 2 and eNOS gene polymorphisms in T2D, suggesting a new genetic susceptibility factor for insulin resistance and hyperlipidemia in T2D.
- Published
- 2014
19. Corrigendum to 'Sequence-structure based phylogeny of GPCR Class A Rhodopsin receptors' [Mol. Phylogenet. Evol. 74 (2014) 66–96]
- Author
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Kavita Kumari Kakarala and Kaiser Jamil
- Subjects
Genetics ,biology ,Phylogenetics ,Rhodopsin ,Mole ,biology.protein ,Computational biology ,Receptor ,Sequence structure ,Molecular Biology ,Ecology, Evolution, Behavior and Systematics ,G protein-coupled receptor - Published
- 2014
20. Genetic Variation in MicroRNAs and Risk of Oral Squamous Cell Carcinoma in South Indian Population
- Author
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Kaiser Jamil, Pulivarthi Sushma, M Ramakrishna, U Satyanarayana, B Triveni, and P. Uday Kumar
- Subjects
Oncology ,Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Pathology ,Epidemiology ,Population ,India ,Single-nucleotide polymorphism ,Biology ,Polymerase Chain Reaction ,Polymorphism, Single Nucleotide ,Young Adult ,Risk Factors ,Internal medicine ,Genetic variation ,Genotype ,medicine ,Carcinoma ,Humans ,Genetic Predisposition to Disease ,education ,Aged ,Mouth neoplasm ,education.field_of_study ,Squamous Cell Carcinoma of Head and Neck ,Public Health, Environmental and Occupational Health ,Middle Aged ,medicine.disease ,Genotype frequency ,stomatognathic diseases ,MicroRNAs ,Head and Neck Neoplasms ,Carcinoma, Squamous Cell ,Female ,Mouth Neoplasms ,Restriction fragment length polymorphism ,Polymorphism, Restriction Fragment Length - Abstract
Background MicroRNAs (miRNAs) are small non-coding RNA molecules, implicated in several activities like initiation, progression and prognosis of various cancers. Single nucleotide polymorphisms (SNPs) in miRNA genes can lead to alteration in mRNA expression, resulting in diverse functional consequences. The aim of our study was to investigate the association of miR-149C>T and miR-196a2C>T SNPs with susceptibility to development of oral squamous cell carcinoma (OSCC) in South Indian subjects. Materials and methods 100 OSCC patients and 102 healthy controls from the general population were recruited for the study. Genetic analysis was performed by polymerase chain reaction/restriction fragment length polymorphism (PCR/RFLP) as per a standard protocol. Results The genotype frequencies in miR-196a2 polymorphism, of TT, CT and CC in the OSCC patients were 69%,10% and 22% respectively while for control group it was 80%, 15% and 5% respectively. The CC genotype of miR196a2 polymorphism was significantly associated with oral squamous cell carcinoma. The genotype frequencies in miR-149 polymorphisms of CC, CT and TT in the oral squamous cell carcinoma (OSCC) patients were 72%, 22% and 6% respectively and for control group 88%, 12% and 0% respectively. CT and TT genotypes of miR149 polymorphism were found to be significantly associated with OSCC (p = 0.05 and 0.07). Conclusions Our study suggests that miR-196a2C>T and miR-149C>T polymorphisms may play crucial roles in the development of OSCC in South Indian subjects.
- Published
- 2015
21. Association of Vascular Endothelial Growth Factor A (VEGFA) and its Receptor (VEGFR2) Gene Polymorphisms with Risk of Chronic Myeloid Leukemia and Influence on Clinical Outcome
- Author
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A. V. N. Swamy, Kaiser Jamil, Vijay Kumar Kutala, Atya Kapley, Raghunadharao Digumarti, Sangeetha Aula, and Samyuktha Lakkireddy
- Subjects
0301 basic medicine ,Adult ,Male ,Vascular Endothelial Growth Factor A ,Genotyping Techniques ,Molecular Sequence Data ,India ,Biology ,Polymerase Chain Reaction ,Polymorphism, Single Nucleotide ,Pathogenesis ,03 medical and health sciences ,0302 clinical medicine ,Polymorphism (computer science) ,Risk Factors ,hemic and lymphatic diseases ,Leukemia, Myelogenous, Chronic, BCR-ABL Positive ,Genotype ,Genetics ,medicine ,Humans ,Genetic Predisposition to Disease ,neoplasms ,Alleles ,Pharmacology ,Base Sequence ,L-Lactate Dehydrogenase ,Case-control study ,Myeloid leukemia ,Kinase insert domain receptor ,General Medicine ,Sequence Analysis, DNA ,medicine.disease ,Vascular Endothelial Growth Factor Receptor-2 ,Up-Regulation ,Leukemia ,Vascular endothelial growth factor A ,030104 developmental biology ,030220 oncology & carcinogenesis ,Case-Control Studies ,Cancer research ,Molecular Medicine ,Female ,Polymorphism, Restriction Fragment Length - Abstract
Vascular endothelial growth factor A (VEGFA) and its kinase insert domain receptor (VEGFR2/KDR) were reported to be upregulated in chronic myeloid leukemia (CML); however, the influence of polymorphisms in VEGFA and VEGFR2 in CML pathogenesis and therapeutic response, have not yet been elucidated.We aimed to analyze these polymorphisms in 212 CML patients and 212 healthy controls by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) approach.The VEGFA+936CT polymorphism did not differ significantly between the CML patients and controls. The frequency of CT genotype was higher in CML patients than in controls (25 vs. 18%), higher in males than in females (29 vs. 18%), was more prevalent in the patients with splenomegaly (p = 0.03), and was negatively associated with lactate dehydrogenase (LDH) levels (p = 0.01). The frequency of VEGFR2 mutant T-allele was higher in CML patients than controls (p0.0001). In the dominant model, patients having the combined AT and TT genotypes were associated with 2.6-fold higher risk of CML [odds ratio (OR) = 2.6, 95% confidence interval (CI) = 1.71–3.97, p0.0001]. VEGFR2 AT genotype was significantly associated with high blast count (p = 0.006), minor hematological response (p = 0.03) and poor cytogenetic response (p = 0.003), indicating its role in therapeutic resistance. In contrast, poor molecular response was observed in patients with TT genotype (p = 0.02). VEGFA+936CT polymorphism was found to have synergistic interaction with VEGFR2+1416AT in inflating the risk for CML further (P(interaction) = 0.0002).Our results indicate that VEGFR2+1416AT polymorphism may be a useful marker in assessing the disease progression in CML patients. In addition, VEGFA+936CT was observed to have additive effect in inflating the risk further.
- Published
- 2015
22. Correlation and Identification of Variable number of Tandem repeats of eNOS Gene in Coronary artery disease (CAD)
- Author
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Moin Uddin Biyabani, Rabbani Syed, Shiva Prasad, Kaiser Jamil, and Farha Deeba
- Subjects
Nitric oxide (NO) ,medicine.medical_specialty ,Bioinformatics ,Coronary artery disease ,Polymorphism (computer science) ,Enos ,Internal medicine ,Genotype ,medicine ,cardiovascular diseases ,GeneralLiterature_REFERENCE(e.g.,dictionaries,encyclopedias,glossaries) ,Allele frequency ,ComputingMilieux_MISCELLANEOUS ,Agricultural and Biological Sciences(all) ,biology ,Nitric oxide synthase ,Gene polymorphism ,biology.organism_classification ,medicine.disease ,Genotype frequency ,Coronary artery disease (CAD) ,Variable number tandem repeat ,Endocrinology ,Original Article ,General Agricultural and Biological Sciences - Abstract
Endothelium-derived nitric oxide (NO) is synthesized from l-arginine by endothelial nitric oxide synthase (eNOS) encoded by the NOS3 gene on chromosome7. Since reduced NO synthesis has been implicated in the development of coronary atherosclerosis; polymorphisms of NOS gene might be associated with increased susceptibility to coronary artery disease (CAD). We therefore undertook this study to determine the association between the occurrence of CAD and eNOS4 b/a polymorphism in South Indian patients. We investigated the polymorphisms in the 27 base-pair tandem repeats in intron4 of the eNOS gene in 100 unrelated CAD patients with positive coronary angiograms and 100 age and sex matched control subjects without any history of symptomatic CAD. The eNOS gene intron4 b/a VNTR polymorphism was analyzed by polymerase chain reaction. The plasma lipids levels and other risk factors were also determined. The genotype frequencies for eNOS4b/b, eNOS4a/b and eNOS4a/a were 63, 26 and 11 per cent in CAD subjects, and 72, 20 and 8 per cent in control subjects, respectively. The genotype frequencies did not differ significantly between the two groups. The frequency of the a allele was 0.24 per cent in CAD subjects and 0.18 per cent in control subjects and no significant association was found between patients and control group (P=0.57, Odds ratio=3.62). Plasma lipids, glucose and creatinine levels were significantly increased in CAD group. The genotypic frequencies and the allele frequency did not differ significantly between the CAD patients and controls indicating that this polymorphism was not an independent risk factor for the development of CAD in South Indian patients.
- Published
- 2010
23. Thymidylate synthase gene polymorphisms effecting 5-FU response in breast cancer patients
- Author
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Kalyana Kumar, Kaiser Jamil, and Mohana Vamsy
- Subjects
Antimetabolites, Antineoplastic ,Cancer Research ,Breast Neoplasms ,Single-nucleotide polymorphism ,Drug resistance ,Pharmacology ,Polymorphism, Single Nucleotide ,Thymidylate synthase ,Breast cancer ,Genotype ,Biomarkers, Tumor ,Genetics ,Genetic predisposition ,medicine ,Humans ,Allele ,Allele frequency ,biology ,Thymidylate Synthase ,General Medicine ,medicine.disease ,Enhancer Elements, Genetic ,Oncology ,Drug Resistance, Neoplasm ,Cancer research ,biology.protein ,Female ,Fluorouracil ,Menopause - Abstract
Our study supports the Drug-Gene Interaction principle, where patients experience adverse drug reactions (ADRs) due to genetic predisposition or due to single nucleotide polymorphisms (SNPs) in drug metabolizing genes. The target enzyme for 5- Fluorouracil is thymidylate synthase (TYMS) this enzyme is also involved in folate metabolism. We determined the frequencies of polymorphisms in drug metabolizing enzyme like TYMS and correlated the drug response in 140 breast cancer patients compared to 150 controls, using PCR and RFLP method. In our results the TYMS1494del polymorphism was statistically significant; allele frequencies for 6bp deletion and 6bp insertion were 0.85 and 0.15 in BC (Breast Cancer) patients compared with 0.95 and 0.04 in controls. The enhancer region 2R/3R heterozygote genotypes were found to be not significant for BC risk. In this study combined genotypes showed 2 fold increased risk of BC. Frequency distribution of 2R and 3R allele among BC patients was 0.85 and 0.15 and 0.95 and 0.04 in controls respectively. Correlation analysis of TYMS enhancer region polymorphisms with drug response suggested that the response was poor in BC patients with 2R/3R and 2R/2R genotypes, but patients with poor response were fewer in number, that this gene may be important in drug response. Genetic screening of the drug metabolizing enzyme like TYMS for the presence of polymorphisms in breast cancer patients will become increasingly useful in individualizing drug therapy.
- Published
- 2010
24. Phylogenetic analysis of ALAD and MGP genes related to lead toxicity
- Author
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Muhummadh Khan, Kaiser Jamil, and AP Shaik
- Subjects
Insecta ,Sequence analysis ,Health, Toxicology and Mutagenesis ,Toxicology ,Mega ,Sequence Analysis, Protein ,Phylogenetics ,Animals ,Humans ,Genetic Predisposition to Disease ,Chordata ,Databases, Protein ,Gene ,Phylogeny ,Genetics ,Extracellular Matrix Proteins ,Polymorphism, Genetic ,Multiple sequence alignment ,Bacteria ,biology ,Phylogenetic tree ,Porphobilinogen synthase ,Calcium-Binding Proteins ,Fungi ,Public Health, Environmental and Occupational Health ,Porphobilinogen Synthase ,Archaea ,Lead Poisoning ,Dehydratase ,biology.protein - Abstract
Experimental studies in our laboratory have established the role of δ-aminolevulinic acid dehydratase (ALAD) and matrix γ-carboxyglutamic acid (MGP) gene polymorphisms in the etiology of lead toxicity. Polymorphisms in these genes influenced the levels of lead in subjects exposed to this metal. In extension to our studies, we aimed to investigate the possible role of these proteins in evolution by studying the phylogenetic relationship and divergence of ALAD and MGP genes using computational phylogenetic methods. The human ALAD and MGP protein sequences from various species were retrieved from Swiss-Prot database and were compared using Basic Local Alignment Search Tool. Multiple sequence alignment was carried out using ClustalW with defaults, and phylogenetic trees for both the genes were built using neighbor-joining method as in Mega software. Our study indicated that ALAD is a highly conserved protein with the same metal binding site distributed in all the phyla (from archaea to chordates). Phylogenetic analysis of MGP gene revealed that it had an important role in the evolution of endogenous skeleton in contrast to exoskeleton of insects. Occurrence of these genes in evolution with conserved metal binding sites strengthens the role of ALAD and MGP genes in regulating heme biosynthesis and mineralization, respectively, in evolution and helps in better understanding of lead poisoning.
- Published
- 2009
25. Polymorphisms in MGP gene and their association with lead toxicity
- Author
-
Kaiser Jamil and Abjal Pasha Shaik
- Subjects
Vitamin ,Adult ,Male ,Adolescent ,Genotype ,Health, Toxicology and Mutagenesis ,Population ,Single-nucleotide polymorphism ,Toxicology ,Polymerase Chain Reaction ,Polymorphism, Single Nucleotide ,Restriction fragment ,chemistry.chemical_compound ,Hemoglobins ,Young Adult ,Humans ,Allele ,education ,MGP gene polymorphisms ,DNA Primers ,education.field_of_study ,Extracellular Matrix Proteins ,Blood lead levels ,biology ,Base Sequence ,Calcium-Binding Proteins ,Promoter ,Lead toxicity ,Middle Aged ,Molecular biology ,PCR ,chemistry ,Lead ,Toxicity ,biology.protein ,Female ,Polymorphism, Restriction Fragment Length ,Research Article - Abstract
Matrix gamma-carboxy glutamic acid protein (MGP) is a 10-kDa secreted protein containing five residues of the vitamin K-dependent calcium binding amino acid gamma-carboxyglutamic acid (Gla). This study was carried out to examine the effects of MGP gene promoter polymorphism (T-138C) on blood lead levels (BLL) and hematological parameters in 113 battery manufacturing unit workers occupationally exposed to lead and 102 controls. Genotypes for the MGP T-138C polymorphism were determined by PCR and restriction fragment length digestion. BLL were determined by Anode Stripping Voltammetry using ESA Model 3010B Lead analyzer. Complete blood picture (CBP) was analyzed using ADVIA Cell counter for each sample. The frequencies of MGP-TT, CT and CC genotypes in our population were 38.6%, 44.3%, and 17.2%, respectively. The frequencies for T and C alleles were 0.612 and 0.386, respectively. Although BLL did not differ significantly among genotypes; they were higher in workers with TT/CT genotype compared to CC genotype subjects (76-88 microg/dL vs 22-45 microg/dL, p0.05). About 29.2% of volunteers (n = 33) from the occupationally exposed group had hemoglobin levels below 10.0 gms/dl. There was no significant difference in total white cell count and platelet count between occupational and non-exposed groups. The possible role of SNPs in the promoter region of MGP gene with relation to lead toxicity was investigated for the first time in the Indian population; although significance could not be achieved in this study, further assessments over a larger population size may help in better understanding of the consequences of lead exposure.
- Published
- 2009
26. Novel mutations of CYP3A4 in fine needle aspiration cytology samples of breast cancer patients and its clinical correlations
- Author
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K. Suseela, M. Ch. Vamsy, G. Suman, and Kaiser Jamil
- Subjects
Adult ,Cancer Research ,Biopsy, Fine-Needle ,Mutant ,Breast Neoplasms ,Biology ,Polymerase Chain Reaction ,Polymorphism, Single Nucleotide ,Breast cancer ,Biomarkers, Tumor ,Genetics ,medicine ,Cytochrome P-450 CYP3A ,Humans ,Coding region ,Allele ,Gene ,Aged ,Neoplasm Staging ,Aged, 80 and over ,COLD-PCR ,Point mutation ,Carcinoma, Ductal, Breast ,Wild type ,General Medicine ,Middle Aged ,Prognosis ,medicine.disease ,Molecular biology ,Gene Expression Regulation, Neoplastic ,Survival Rate ,Oncology ,Mutation ,Female - Abstract
Human Cytochrome P450 3A4 is a major P450 enzyme in the liver and gastrointestinal tract. It plays an important role in the metabolism of a wide variety of drugs, some endogenous steroids, and harmful environmental contaminants. To investigate the interindividual variation in CYP3A4 levels we have carried out a study on the genetic polymorphism of 100 breast cancer subjects using fine needle aspiration cytology (FNAC) sampling procedure. DNA was extracted from all the samples and PCR was carried out for detecting the CYP3A4 gene polymorphisms. We selected exon-7 and 10 which are present on the 5'-flanking coding region of the gene using the respective primers for PCR followed by direct automated sequencing method for detecting the mutations. These mutations were compared to the wild type sequence structures obtained from GenBank database (accession no. AF209389). We found two novel point mutations which are heterozygous mutant alleles. The two variant alleles were Ile222Arg and Phe175Val occurring in coding region of exon-7. Ile222Arg mutation was found in 3 malignant cases whereas Phe175Val mutation was found in 4 malignant cases. This is the first report of these two novel point mutations in CYP3A4 gene. These mutations in the gene in respective patients were found to relate to drug response in invasive ductal carcinomas of breast cancer.
- Published
- 2009
27. Homology models of the mutated EGFR and their response towards quinazolin analogues
- Author
-
Sabitha Kotra, Kishore Kumar Madala, and Kaiser Jamil
- Subjects
Models, Molecular ,Stereochemistry ,Molecular Sequence Data ,Mutation, Missense ,Ligands ,Protein Structure, Secondary ,Receptor tyrosine kinase ,chemistry.chemical_compound ,Gefitinib ,Catalytic Domain ,Materials Chemistry ,medicine ,Quinazoline ,Amino Acid Sequence ,Epidermal growth factor receptor ,Homology modeling ,Amino Acids ,Physical and Theoretical Chemistry ,Protein Kinase Inhibitors ,Spectroscopy ,Binding Sites ,biology ,Chemistry ,Computer Graphics and Computer-Aided Design ,ErbB Receptors ,Biochemistry ,Structural Homology, Protein ,Docking (molecular) ,Quinazolines ,biology.protein ,Thermodynamics ,Mutant Proteins ,Erlotinib ,Sequence Alignment ,Tyrosine kinase ,medicine.drug - Abstract
One of the most intensely studied tyrosine kinases is the epidermal growth factor receptor (EGFR). The tyrosine kinase receptors are known to be over expressed in some solid tumors and non-small cell lung cancers, causing differential susceptibility to the quinazoline inhibitors. In this study we have taken SYK tyrosine kinase coordinates from PDB database to model two new EGFR receptors with these mutations G695S and L834R and conducted all the docking studies of the inhibitors, also evaluated these two models for quality of structure using PROCHECK. Seven quinazoline analogues (gefitinib, erlotinib, CI-1033, and EKB-569 and other analogues) were selected for comparisons among the two new models. This study determined the receptor/inhibitor interactions, at that active domain binding sites consisting of 15 amino acids. We were able to calculate the energy data for each of the seven inhibitors. This data has been important in interpreting the affinity between the inhibitors evaluated against the three models of EGFR (wild-type and two mutated types). "Affinity"-based studies have indicated the order of response based on docking energy levels (Van der Waals and electrostatic interactions). The active ATP binding sites consisting of 15 amino acid residues were identified and the total energy (E(total)) which showed the affinity between the inhibitor molecules and the receptor (Van der Waals and electrostatic interactions). The selection of the quinazoline analogues was purely on their emergence as possible candidates in the drug discovery areas. This study describes the successful application of these models that we constructed for molecular docking studies to rationally design compounds predicted to bind favorably to the modeled EGFR catalytic sites.
- Published
- 2008
28. Genomic Distribution, Expression and Pathways of Cancer Metasignature Genes Through Knowledge Based Data Mining
- Author
-
Kaiser Jamil and Muhummadh Khan
- Subjects
Cancer Research ,Oncology ,Expression (architecture) ,medicine ,Cancer ,Distribution (pharmacology) ,Data mining ,Biology ,medicine.disease ,computer.software_genre ,Gene ,computer - Published
- 2008
29. A study on the ALAD gene polymorphisms associated with lead exposure
- Author
-
Abjal Pasha Shaik and Kaiser Jamil
- Subjects
Adult ,Male ,Adolescent ,Genotype ,Health, Toxicology and Mutagenesis ,India ,Toxicology ,Lead poisoning ,Hemoglobins ,Young Adult ,Occupational Exposure ,medicine ,Humans ,Genetic Predisposition to Disease ,Gene ,Genetics ,biology ,Porphobilinogen synthase ,Public Health, Environmental and Occupational Health ,Porphobilinogen Synthase ,Middle Aged ,medicine.disease ,Lead Poisoning ,Lead ,Dehydratase ,Toxicity ,Lead exposure ,biology.protein ,Female ,Occupational exposure ,Polymorphism, Restriction Fragment Length - Abstract
δ-aminolevulinic acid dehydratase (ALAD) plays an important role in lead poisoning, and polymorphisms in this gene may affect the response of individuals to lead toxicity symptoms. This study was carried out to examine the effects of ALAD gene polymorphism (G177C) on blood lead levels (BLL) and hematological parameters. In all, 113 battery manufacturing unit workers and 102 occupationally unexposed controls from Hyderabad, A.P, India formed the study group. Genotypes for the ALAD G177C polymorphism were determined by Polymerase chain reaction and restriction fragment length digestion. BLL were determined by anode stripping voltammetry using ESA Model 3010B Lead analyzer. Complete blood picture was analyzed using ADVIA cell counter for each sample. The frequencies for ALAD1 and ALAD2 alleles were 0.98 and 0.01, respectively. ALAD 1-2 and ALAD 2-2 genotypes together were considered as a single group and compared with the ALAD 1-1 genotype group. BLL did not differ significantly among ALAD1-1, 1-2, and 2-2 genotypes; however, subjects from the ALAD 1-2/2-2 genotype group showed higher BLL concentrations of 80.51 μg/dL when compared with subjects from the ALAD 1-1 genotype group (50.4 μg/dL). Approximately 29.2% volunteers ( n = 33) from the occupationally exposed group had hemoglobin levels below 10.0 g/dL. There was no significant difference in total white cell count and platelet count between occupational and non-exposed lead-exposed groups. BLL of occupationally exposed individuals were significantly high compared with the unexposed group. ALAD G177C polymorphism along with BLL and assessment of hematological parameters may play an important role in evaluation and better understanding of the consequences of lead exposure.
- Published
- 2008
30. Study on the Conserved and the Polymorphic Sites of MTHFR Using Bioinformatics Approaches
- Author
-
Muhummadh Khan and Kaiser Jamil
- Subjects
Genetics ,Computational Theory and Mathematics ,biology ,Methylenetetrahydrofolate reductase ,biology.protein ,Computer Science Applications - Published
- 2008
31. Determination of AChE levels and genotoxic effects in farmers occupationally exposed to pesticides
- Author
-
Rambabu Naravaneni and Kaiser Jamil
- Subjects
Adult ,Time Factors ,DNA damage ,Aché ,Health, Toxicology and Mutagenesis ,Down-Regulation ,India ,Poison control ,Physiology ,Biology ,Toxicology ,medicine.disease_cause ,Risk Assessment ,030226 pharmacology & pharmacy ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Occupational Exposure ,medicine ,Humans ,Lymphocytes ,030212 general & internal medicine ,Pesticides ,Chromosome Aberrations ,Dose-Response Relationship, Drug ,General Medicine ,Middle Aged ,Pesticide ,Acetylcholinesterase ,language.human_language ,Agricultural Workers' Diseases ,Comet assay ,chemistry ,Case-Control Studies ,Toxicity ,language ,Colorimetry ,Comet Assay ,Seasons ,Biomarkers ,Genotoxicity ,DNA Damage ,Mutagens - Abstract
Pesticides can cause cytogenetic effects and lower the acetyl cholinesterase (AChE) levels in farmers exposed to pesticides. In this study, 210 farmers exposed to pesticides and 160 non-exposed individuals were enrolled for determining the genotoxicity and AChE levels. The AChE levels were determined in plasma and RBC lysate from blood samples collected from farmers and control subjects. AChE (true and pseudo) estimation done by the colorimetric method revealed that there was a progressive fall in both the RBC and plasma AChE levels in exposed individuals compared to unexposed individuals, which correlated with the severity of exposure (253.5 versus 311.1 and 142.3 versus 152.1; P < 0.001). Cytogenetic studies showed an increase in DNA damage and higher chromosomal aberrations (CAs) in exposed farmers compared to the control subjects (26.13 versus 07.61 and 21.37 versus 1.52; P < 0.001). When comparing the AChE levels with DNA damage and structural CA frequencies, there was a negative linear correlation. Therefore based on these findings, it is concluded that genotoxic biomarkers like CA frequencies, DNA damage data along with AChE levels are important parameters for determining farmer's health who are exposed to pesticides in any situation. Human & Experimental Toxicology (2007) 26, 723—731
- Published
- 2007
32. Biased signaling: potential agonist and antagonist of PAR2
- Author
-
Kavita Kumari Kakarala and Kaiser Jamil
- Subjects
0301 basic medicine ,Agonist ,Models, Molecular ,medicine.drug_class ,In silico ,Molecular Conformation ,Drug design ,Pharmacology ,Biology ,Molecular Dynamics Simulation ,Substance K ,Ligands ,03 medical and health sciences ,Structural Biology ,Drug Discovery ,medicine ,Receptor, PAR-2 ,Receptor ,Molecular Biology ,Protease-activated receptor 2 ,G protein-coupled receptor ,Binding Sites ,General Medicine ,Cell biology ,Molecular Docking Simulation ,030104 developmental biology ,Drug development ,Drug Design ,Protein Binding ,Signal Transduction - Abstract
Protease activated receptor 2 (PAR2) has emerged as one of the promising therapeutic targets to inhibit rapidly metastasizing breast cancer cells. However, its elusive molecular mechanism of activation and signaling has made it a difficult target for drug development. In this study, in silico methods were used to unfold PAR2 molecular mechanism of signaling based on the concept of GPCR receptor plasticity. Although, there are no conclusive evidences of the presence of specific endogenous ligands for PAR2, the efficacy of synthetic agonist and antagonist in PAR2 signaling has opened up the possibilities of ligand-mediated signaling. Furthermore, it has been proved that ligands specific for one GPCR can induce signaling in GPCRs belonging to other subfamilies. Therefore, the aim of this study was to identify potential agonists and antagonists from the GPCR ligand library (GLL), which may induce biased signaling in PAR2 using the concept of existence of multiple ligand-stabilized receptor conformations. The results of our in silico study suggest that PAR2 may show biased signaling mainly with agonists of serotonin type 1, β-adrenergic type 1,3 and antagonists of substance K (NK1), serotonin type 2, dopamine type 4, and thromboxane receptors. Further, this study also throws light on the putative ligand-specific conformations of PAR2. Thus, the results of this study provide structural insights to putative conformations of PAR2 and also gives initial clues to medicinal chemists for rational drug design targeting this challenging receptor.
- Published
- 2015
33. Association of MDR1 gene (C3435T) polymorphism and gene expression profiling in lung cancer patients treated with platinum-based chemotherapy
- Author
-
Kaiser Jamil, Syed Subhani, and Sharanabasappa Somanath Nirni
- Subjects
Oncology ,Adult ,Male ,medicine.medical_specialty ,ATP Binding Cassette Transporter, Subfamily B ,Lung Neoplasms ,Genotype ,Paclitaxel ,medicine.medical_treatment ,Antineoplastic Agents ,Biology ,Polymorphism, Single Nucleotide ,Polymorphism (computer science) ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Genetics ,Carcinoma ,medicine ,Humans ,Lung cancer ,Genetic Association Studies ,Aged ,Pharmacology ,Chemotherapy ,Lung ,Gene Expression Profiling ,Cancer ,General Medicine ,Middle Aged ,medicine.disease ,Up-Regulation ,Radiation therapy ,medicine.anatomical_structure ,Treatment Outcome ,Molecular Medicine ,Cisplatin - Abstract
Chemotherapy is the standard and recommended treatment for lung cancer apart from surgery and radiotherapy. Chemotherapy is administered as mono-agents or as combination therapy. In this study, we examined the role of MDR1 C3435T polymorphisms in lung cancer patients undergoing chemotherapy. We genotyped 126 cases with lung cancer and 111 healthy controls, using the polymerase chain reaction–restriction fragment length polymorphism method (PCR–RFLP). Frequencies of MDR1 C3435C, C3435T and T3435T genotypes were 61, 16 and 23 % in lung cancer patients and 86, 9 and 5 % in the controls, respectively. The T3435T genotypes had a 5.23-fold increased risk for lung cancer. (OR 5.23; 95 % CI 2.082–13.146; p = 0.0004). Patients with TT genotypes were more frequent in stage IV and were significantly associated with the disease (p = 0.05). Habitual smoker lung cancer patients were 50 % CC genotypes whereas TT genotypes were 34 %. The non-smokers had 46 % CC genotypes and 23 % TT genotypes. Furthermore, we collected tissue biopsy samples for expression analysis from 20 patients (for controls we used the non-cancerous region of the same tissue). The present study showed mRNA expression of MDR1 was up-regulated in 80 % of the cancer group in comparison with the control group (p = 0.0002). We also correlated the association between MDR1 genotypes with different combinations of chemotherapy. The combinations and genotype distributions in the group receiving paclitaxel + cisplatin were as follows: CC (67 %), CT (24 %) and TT (9 %) genotypes, respectively, and the group receiving carboplatin + gemcitabine CC (46 %), CT (19 %) and TT (35 %) genotypes, respectively. We found that MDR1 (rs1045642) C3435T polymorphism and gene expression was significantly associated with the clinical outcome in lung carcinoma patients. In conclusion, it is suggested that MDR1 TT genotypes had higher risk for the development of lung cancer. Also, this polymorphism could be used as a genetic marker for predicting the clinical outcome of lung cancer patients.
- Published
- 2015
34. Expression of surfactant proteins SP-A and SP-D in murine decidua and immunomodulatory effects on decidual macrophages
- Author
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Uday Kishore, Lubna Kouser, Hrishikesh Pandit, Aghila Rani Koippallil Gopalakrishnan, Shanmuga Priyaa Madhukaran, Fatimah S. Alhamlan, Eswari Dodagatta Marri, Kaiser Jamil, and Taruna Madan
- Subjects
0301 basic medicine ,Lipopolysaccharides ,Stromal cell ,Lipopolysaccharide ,Immunology ,Primary Cell Culture ,Inflammation ,Biology ,Flow cytometry ,Andrology ,03 medical and health sciences ,chemistry.chemical_compound ,Mice ,Fetus ,Pregnancy ,medicine ,Decidua ,Immunology and Allergy ,Animals ,Decidual cells ,Innate immune system ,medicine.diagnostic_test ,Pulmonary Surfactant-Associated Protein A ,Tumor Necrosis Factor-alpha ,Macrophages ,Hematology ,Pulmonary Surfactant-Associated Protein D ,Antigens, Differentiation ,Mice, Inbred C57BL ,030104 developmental biology ,medicine.anatomical_structure ,chemistry ,Gene Expression Regulation ,Tumor necrosis factor alpha ,Female ,medicine.symptom ,Stromal Cells - Abstract
Surfactant proteins SP-A and SP-D are pattern recognition innate immune molecules that belong to the C-type lectin family. In lungs, they play an important role in the clearance of pathogens and control of inflammation. SP-A and SP-D are also expressed in the female reproductive tract where they play an important role in pregnancy and parturition. However, the role of SP-A and SP-D expressed at the feto-maternal interface (decidua) remains unclear. Here, we have examined the expression of SP-A and SP-D in the murine decidua at 17.5 (pre-parturition) and 19.5dpc (near parturition) and their effect on lipopolysaccharide (LPS)-treated decidual macrophages. SP-A and SP-D were localized to stromal cells in the murine decidua at 17.5 and 19.5dpc in addition to cells lining the maternal spiral artery. Purified pre-parturition decidual cells were challenged with LPS with and without SP-A or SP-D, and expression of F4/80 and TNF-α were measured by flow cytometry. On their own, SP-A or SP-D did not affect the percentage of F4/80 positive cells while they suppressed the percentage of TNF-α positive cells. However, simultaneous addition of SP-A or SP-D, together with LPS, reduced TNF-α secreting F4/80 positive cells. It is likely that exogenous administration of SP-A and SP-D in decidua can potentially control infection and inflammation mediators during spontaneous term labor and infection-induced preterm labor. Thus, the presence of SP-A and SP-D in the murine decidua is likely to play a protective role against intrauterine infection during pregnancy.
- Published
- 2015
35. Transcriptional factor PU.1 regulates decidual C1q expression in early pregnancy in human
- Author
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Jinhua Lu, Shanmuga Priyaa Madhukaran, Uday Kishore, Mahesh Choolani, Boon Heng Dennis Teo, and Kaiser Jamil
- Subjects
lcsh:Immunologic diseases. Allergy ,Transcriptional factor ,Reproduction (economics) ,Immunology ,Academic practice ,Early pregnancy factor ,chemical and pharmacologic phenomena ,Biology ,Pregnancy ,Decidua ,Immunology and Allergy ,implantation ,License ,C1q ,Stromal cells ,transcription factor ,Law and economics ,Original Research ,Trophoblast ,Creative commons ,trophoblast ,Implantation ,Expression (architecture) ,biology.protein ,Transcription factor ,Stromal Cells ,lcsh:RC581-607 ,c1q - Abstract
"Copyright: © 2015 Madhukaran, Kishore, Jamil, Teo, Choolani and Lu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms." C1q is the first recognition subcomponent of the complement classical pathway, which in addition to being synthesized in the liver, is also expressed by macrophages and dendritic cells (DCs). Trophoblast invasion during early placentation results in accumulation of debris that triggers the complement system. Hence, both early and late components of the classical pathway are widely distributed in the placenta and decidua. In addition, C1q has recently been shown to significantly contribute to feto-maternal tolerance, trophoblast migration, and spiral artery remodeling, although the exact mechanism remains unknown. Pregnancy in mice, genetically deficient in C1q, mirrors symptoms similar to that of human preeclampsia. Thus, regulated complement activation has been proposed as an essential requirement for normal successful pregnancy. Little is known about the molecular pathways that regulate C1q expression in pregnancy. PU.1, an Ets-family transcription factor, is required for the development of hematopoietic myeloid lineage immune cells, and its expression is tissue-specific. Recently, PU.1 has been shown to regulate C1q gene expression in DCs and macrophages. Here, we have examined if PU.1 transcription factor regulates decidual C1q expression. We used immune-histochemical analysis, PCR, and immunostaining to localize and study the gene expression of PU.1 transcription factor in early human decidua. PU.1 was highly expressed at gene and protein level in early human decidual cells including trophoblast and stromal cells. Surprisingly, nuclear as well as cytoplasmic PU.1 expression was observed. Decidual cells with predominantly nuclear PU.1 expression had higher C1q expression. It is likely that nuclear and cytoplasmic PU.1 localization has a role to play in early pregnancy via regulating C1q expression in the decidua during implantation.
- Published
- 2015
36. Homology Modelling and Docking Studies of Human α2-Adrenergic Receptor Subtypes
- Author
-
Archana Jayaraman, Kavita Kumari Kakarala, and Kaiser Jamil
- Subjects
Drug ,media_common.quotation_subject ,Computational biology ,Pharmacology ,Biology ,Homology (biology) ,chemistry.chemical_compound ,chemistry ,Docking (molecular) ,In vivo ,Binding site ,Neurotransmitter ,Receptor ,media_common ,G protein-coupled receptor - Abstract
α2-adrenergic receptors play a key role in the regulation of sympathetic system, neurotransmitter release, blood pressure and intraocular pressure. Although α2-adrenergic receptors mediate a number of physiological functions in vivo and have great therapeutic potential, the absence of crystal structure of α2-adrenergic receptor subtypes is a major hindrance in the drug design efforts. The therapeutic efficacy of the available drugs is not selective for subtype specificity (α2a, α2b and α2c) leading to unwanted side effects. We used Homology modelling and docking studies to understand and analyze the residues important for agonist and antagonist binding. We have also analyzed binding site volume, and the residue variations which may play important role in ligand binding. We have identified residues through our modelling and docking studies, which would be critical in giving subtype specificity and may help in the development of future subtype-selective drugs.
- Published
- 2015
37. Application of Human Lymphocytes for Evaluating Toxicity of Anti-Cancer Drugs
- Author
-
G. Suman and Kaiser Jamil
- Subjects
Pharmacology ,Cisplatin ,Biology ,medicine.disease_cause ,Carboplatin ,Comet assay ,chemistry.chemical_compound ,chemistry ,Toxicity ,Cancer cell ,medicine ,MTT assay ,Viability assay ,Genotoxicity ,medicine.drug - Abstract
Important discoveries came forth when human cell lines were used for screening drugs and other chems. This investigation dets. the toxicity profiles of neoplastic drugs utilizing human lymphocytes from peripheral blood samples of healthy non-smoking donors and the blood samples of cancer patients suffering from acute myeloid leukemia (AML) were collected. The order of toxicities (LC50) using MTT assay was found to be as follows; Cisplatin > Carboplatin > Cyclophosphamide > 5-FU > Vincristine. The values were calcd. using statistical anal. The MTT assay is now widely adopted by researchers and industry, as it is a rapid Spectrophotometric method for detg. cell viability in cells. The changes induced by individual drugs could be unique to each compd. which might reflect in genotoxicity, hence utilizing the Single Cell Gel Electrophoresis (SCGE) assay, genotoxicity of the drugs was detd. as comet tails of DNA damages. It was found that the values obtained were significant (p
- Published
- 2006
38. Methylenetetrahydrofolate Reductase (MTHFR) C677T and A1298C Polymorphisms and Breast Cancer in South Indian Population
- Author
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Kaiser Jamil and C. H. Kalyankumar
- Subjects
Oncology ,Gynecology ,Cancer Research ,medicine.medical_specialty ,biology ,business.industry ,medicine.disease ,digestive system diseases ,Breast cancer ,Methylenetetrahydrofolate reductase ,Internal medicine ,biology.protein ,Medicine ,Mthfr c677t ,business ,South indian population ,Allele frequency - Abstract
In this study investigations were made to detect the assocn. of MTHFR C677T and A1298C polymorphisms in breast cancer patients, in the South Indian population. Eighty eight women patients with breast cancer and 95 healthy women as controls were included in the study after their consent to participate in this program. MTHFR gene polymorphisms were detd. by the PCR-RFLP method. The allele frequencies of the MTHFR C677T were 27.84% in the breast cancer subjects and 19.47% in the controls. The allele frequencies of the MTHFR A1298C were 25.56% in the breast cancer subjects and 17.89% in the controls. Frequencies of MTHFR C677C, C677T and T677T were 47.9%, 44.8%, 7.1% in breast cancer patients and 63.2, 34.5 and 4.6% in the controls. Frequencies of MTHFR A1298A, A1298C and C1298C were 54.8, 40.8 and 5.1% in breast cancer patients and 66.9, 30.1 and 2.9% in the controls. When we compared the frequencies of C677T and T677T with C677C, A1298C and C1298C with A1298A, we found less significant assocn. between specific MTHFR variants in breast cancer patients. Our findings suggest that MTHFR C677T and A1298C gene variants do not have a major influence on the susceptibility to breast cancer in south Indian population. [on SciFinder(R)]
- Published
- 2006
39. Cytotoxicity and Genotoxicity Induced by the Pesticide Profenofos on Cultured Human Peripheral Blood Lymphocytes
- Author
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G. Prabhavathy Das, Abjal Pasha Shaik, and Kaiser Jamil
- Subjects
Insecticides ,Cell Survival ,Health, Toxicology and Mutagenesis ,Lymphocyte ,Biology ,Toxicology ,medicine.disease_cause ,chemistry.chemical_compound ,medicine ,Humans ,Lymphocytes ,Cytotoxicity ,Cells, Cultured ,Chromosome Aberrations ,Pharmacology ,Chemical Health and Safety ,Dose-Response Relationship, Drug ,Organothiophosphates ,Organophosphate ,Public Health, Environmental and Occupational Health ,In vitro toxicology ,Trypan Blue ,General Medicine ,Molecular biology ,Solutions ,Comet assay ,medicine.anatomical_structure ,chemistry ,Toxicity ,Trypan blue ,Comet Assay ,Genotoxicity ,DNA Damage ,Mutagens - Abstract
Profenofos is a broad-spectrum organophosphate insecticide and acaricide used widely for agricultural and household purposes. The aim of this investigation was to determine its toxicity profile in vitro, using lymphocytes from peripheral blood samples of healthy human donors. We found the IC(50) of profenofos to be 3.5 microM as measured by Trypan blue dye exclusion method. Chromosomal analyses of the metaphase plates of the samples treated with sublethal concentrations of profenofos revealed satellite associations and chromatid breaks and gaps, indicating its effect on chromosomes. The results were further supported by comet assay, where single-strand breaks in DNA were observed as comet tail lengths. The results were statistically significant (p0.01, ANOVA). Hence, it may be proposed that in vitro assays like the comet assay and chromosomal aberrations test, which indicate genetic damage, could be used to study the effect of organophosphorus pesticide poisoning in humans.
- Published
- 2006
40. Protease activated receptor-2 (PAR2): possible target of phytochemicals
- Author
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Kavita Kumari Kakarala and Kaiser Jamil
- Subjects
In silico ,Phytochemicals ,Breast Neoplasms ,Pharmacology ,Biology ,Breast cancer ,Structural Biology ,medicine ,Humans ,Receptor, PAR-2 ,Computer Simulation ,Receptor ,Molecular Biology ,Protease-activated receptor 2 ,G protein-coupled receptor ,Cell Proliferation ,Binding Sites ,Cell growth ,Cell Cycle ,General Medicine ,medicine.disease ,Docking (molecular) ,Female ,Signal transduction ,Protein Binding ,Signal Transduction - Abstract
The use of phytochemicals either singly or in combination with other anticancer drugs comes with an advantage of less toxicity and minimal side effects. Signaling pathways play central role in cell cycle, cell growth, metabolism, etc. Thus, the identification of phytochemicals with promising antagonistic effect on the receptor/s playing key role in single transduction may have better therapeutic application. With this background, phytochemicals were screened against protease-activated receptor 2 (PAR2). PAR2 belongs to the superfamily of GPCRs and is an important target for breast cancer. Using in silico methods, this study was able to identify the phytochemicals with promising binding affinity suggesting their therapeutic potential in the treatment of breast cancer. The findings from this study acquires importance as the information on the possible agonists and antagonists of PAR2 is limited due its unique mechanism of activation.
- Published
- 2014
41. Antimicrobial Activity of Some Pentacyclic Triterpenes and Their Synthesized 3-O-Lipophilic Chains
- Author
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Uppuluri V. Mallavadhani, Peddi Srinivasa Reddy, Kaiser Jamil, and Anita Mahapatra
- Subjects
Gram-negative bacteria ,Amyrin ,Gram-positive bacteria ,Pharmaceutical Science ,Microbial Sensitivity Tests ,Bacillus subtilis ,Bacillus sphaericus ,chemistry.chemical_compound ,Ursolic acid ,Organic chemistry ,Oleanolic Acid ,Pharmacology ,Bacteria ,Esterification ,biology ,Plant Extracts ,Fatty Acids ,fungi ,General Medicine ,Diospyros ,biology.organism_classification ,Antimicrobial ,Triterpenes ,Anti-Bacterial Agents ,Molecular Weight ,Plant Leaves ,chemistry ,Pentacyclic Triterpenes - Abstract
The major metabolites of Diopsyros melanoxylon viz. amyrins and ursolic acid and their lipophilic 3-O-fatty acid ester chains (C12-C18), which are synthesized now under mild esterification conditions in excellent yields (80-95%), were evaluated for their antimicrobial activity against a series of Gram positive and Gram negative bacteria. Significantly these compounds were found to exhibit potent activity against Gram negative bacteria Pseudomonas syringae (ATCC #13457) and fairly good activity against Gram positive bacteria, Bacillus sphaericus (ATCC #14577) and Bacillus subtilis (ATCC #6051).
- Published
- 2004
42. ANTIMICROBIAL DRUG RESISTANCE IN STRAINS OF Escherichia coli ISOLATED FROM FOOD SOURCES
- Author
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Mohammed Uddin Rasheed, Zelalem Teklemariam, Kaiser Jamil, Parveez Ahamed, and Nooruddin Thajuddin
- Subjects
lcsh:Arctic medicine. Tropical medicine ,lcsh:RC955-962 ,Antibiotic sensitivity ,Colony Count, Microbial ,India ,Pasteurization ,Drug resistance ,Biology ,Microbiology ,beta-Lactam Resistance ,law.invention ,Antibiotic resistance ,Disk Diffusion Antimicrobial Tests ,law ,Drug Resistance, Bacterial ,Escherichia coli ,Animals ,Food microbiology ,Food science ,Raw meat ,E. coli ,Agriculture ,General Medicine ,Antimicrobial ,Anti-Bacterial Agents ,Multiple drug resistance ,Infectious Diseases ,Multidrug resistant ,ESBL ,Food Microbiology ,Medicine ,Cattle - Abstract
A variety of foods and environmental sources harbor bacteria that are resistant to one or more antimicrobial drugs used in medicine and agriculture. Antibiotic resistance in Escherichia coli is of particular concern because it is the most common Gram-negative pathogen in humans. Hence this study was conducted to determine the antibiotic sensitivity pattern of E. coli isolated from different types of food items collected randomly from twelve localities of Hyderabad, India. A total of 150 samples comprising; vegetable salad, raw egg-surface, raw chicken, unpasteurized milk, and raw meat were processed microbiologically to isolate E. coli and to study their antibiotic susceptibility pattern by the Kirby-Bauer method. The highest percentages of drug resistance in isolates of E. coli were detected from raw chicken (23.3%) followed by vegetable salad (20%), raw meat (13.3%), raw egg-surface (10%) and unpasteurized milk (6.7%). The overall incidence of drug resistant E. coli was 14.7%. A total of six (4%) Extended Spectrum β-Lactamase (ESBL) producers were detected, two each from vegetable salads and raw chicken, and one each from raw egg-surface and raw meat. Multidrug resistant strains of E. coli are a matter of concern as resistance genes are easily transferable to other strains. Pathogen cycling through food is very common and might pose a potential health risk to the consumer. Therefore, in order to avoid this, good hygienic practices are necessary in the abattoirs to prevent contamination of cattle and poultry products with intestinal content as well as forbidding the use of untreated sewage in irrigating vegetables. Variedade de alimentos e fontes ambientais contem bactérias resistentes a uma ou mais drogas antimicrobianas usadas em medicina e agricultura. Resistência antibiótica pela Escherichia coli é particularmente preocupante porque ela é o patógeno mais comum Gram negativo em humanos. Portanto este estudo foi conduzido para determinar o aspecto de sensibilidade antibiótica da E. coli isolados de diferentes tipos de alimentos obtidos ao acaso de 12 localidades de Hyderabad, India. Um total de 150 amostras compreendendo saladas, vegetais, superfícies de ovos crus, galinhas cruas, leite não pasteurizado e carne crua foram processados microbiologicamente para isolar E. coli e estudar o quadro de sensibilidade antibiótica pelo método de Kirby-Bauer. A maior percentagem de resistência à droga foi isolada de E. coli obtidos de galinha crua (23,3%) seguido de saladas e vegetais (20%), carne crua (13,3%), superfície do ovo cru (10%) e leite não pasteurizado (6,7%). Incidência total de E. coli resistente foi de 14,7%. Um total de seis (4%) Extended Spectrum β-Lactamase (ESBL) produtores foram detectados, dois cada de salada de vegetais e galinha crua e um cada de superfície de ovo cru e carne crua. Espécies resistentes a múltiplas drogas de E. coli são matéria de preocupação uma vez que os genes de resistência podem facilmente ser transferidos para outras linhagens. O ciclo do patógeno é muito comum nos alimentos e pode ser risco potencial para a saúde do consumidor. Portanto, para evitar isto boas práticas de higiene são necessárias nos abatedouros para prevenir a contaminação de gado e aves com conteúdo intestinal assim como proibir o uso de águas de esgoto não tratadas para irrigar vegetais.
- Published
- 2014
43. Structure and putative signaling mechanism of Protease activated receptor 2 (PAR2) - a promising target for breast cancer
- Author
-
Kavita Kumari Kakarala, Vinod Devaraji, and Kaiser Jamil
- Subjects
Agonist ,Molecular model ,medicine.drug_class ,Molecular Sequence Data ,Antineoplastic Agents ,Breast Neoplasms ,Computational biology ,Biology ,Molecular Dynamics Simulation ,Ligands ,Materials Chemistry ,medicine ,Humans ,Receptor, PAR-2 ,Amino Acid Sequence ,Molecular Targeted Therapy ,Physical and Theoretical Chemistry ,Spectroscopy ,Protease-activated receptor 2 ,Phylogeny ,G protein-coupled receptor ,Binding Sites ,Mechanism (biology) ,Hydrogen Bonding ,Isoxazoles ,Computer Graphics and Computer-Aided Design ,Protein Structure, Tertiary ,Protease-Activated Receptor 1 ,Biochemistry ,Rhodopsin ,Structural Homology, Protein ,biology.protein ,Female ,Oligopeptides ,Function (biology) ,Protein Binding ,Signal Transduction - Abstract
Experimental evidences have observed enhanced expression of protease activated receptor 2 (PAR2) in breast cancer consistently. However, it is not yet recognized as an important therapeutic target for breast cancer as the primary molecular mechanisms of its activation are not yet well-defined. Nevertheless, recent reports on the mechanism of GPCR activation and signaling have given new insights to GPCR functioning. In the light of these details, we attempted to understand PAR2 structure & function using molecular modeling techniques. In this work, we generated averaged representative stable models of PAR2, using protease activated receptor 1 (PAR1) as a template and selected conformation based on their binding affinity with PAR2 specific agonist, GB110. Further, the selected model was used for studying the binding affinity of putative ligands. The selected ligands were based on a recent publication on phylogenetic analysis of Class A rhodopsin family of GPCRs. This study reports putative ligands, their interacting residues, binding affinity and molecular dynamics simulation studies on PAR2-ligand complexes. The results reported from this study would be useful for researchers and academicians to investigate PAR2 function as its physiological role is still hypothetical. Further, this information may provide a novel therapeutic scheme to manage breast cancer.
- Published
- 2014
44. Hypoglycaemic, hypolipidemic and antioxidant properties of tulsi (Ocimum sanctum linn) on streptozotocin induced diabetes in rats
- Author
-
Kaiser Jamil, Eshrat Halim M. A. Hussain, and Mala Rao
- Subjects
chemistry.chemical_classification ,medicine.medical_specialty ,Antioxidant ,biology ,Chemistry ,Thiobarbituric acid ,Glutathione peroxidase ,medicine.medical_treatment ,Diabetes ,Clinical Biochemistry ,Glutathione ,Streptozotocin ,Lipid peroxidation ,Superoxide dismutase ,chemistry.chemical_compound ,Endocrinology ,Internal medicine ,medicine ,TBARS ,biology.protein ,medicine.drug - Abstract
Effect of oral administration of 200 mg/Kg body weight of the aqueous extract ofOcimum sanctum (Tulsi) mixed with diet for eight weeks to diabetic (streptozotocin induced) rats was studied. There was significant reduction in fasting blood glucose, serum lipid profile, lipid peroxidation products, (LPO) and improvement in glucose tolerance. The aqueous extract also decreased LPO formation (thiobarbituric acid reactive substances TBARS) and increased antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), glutathione transferase (GT) and one antioxidant reduced glutathione (GSH) in plasma and rat liver, lung, kidney and brain. The decrease in TBARS and increase in GSH, SOD, CAT, GPX, and GT clearly shows the antioxidant property ofOcimum sanctum.
- Published
- 2001
45. Effects of Vepacide (Azadirachta indica) on asp artate and al anine aminotransferase profiles in a subchronic study with rats
- Author
-
M. K. J. Siddiqui, Mohammed F. Rahman, and Kaiser Jamil
- Subjects
Male ,0301 basic medicine ,Insecticides ,medicine.medical_specialty ,Necrosis ,Health, Toxicology and Mutagenesis ,Administration, Oral ,Aspartate transaminase ,Kidney ,Toxicology ,03 medical and health sciences ,chemistry.chemical_compound ,Sex Factors ,0302 clinical medicine ,Oral administration ,Internal medicine ,medicine ,Animals ,Aspartate Aminotransferases ,Rats, Wistar ,Dose-Response Relationship, Drug ,030102 biochemistry & molecular biology ,biology ,Alanine Transaminase ,General Medicine ,Azadirachta ,biology.organism_classification ,Triterpenes ,Rats ,medicine.anatomical_structure ,Endocrinology ,Liver ,Alanine transaminase ,chemistry ,030220 oncology & carcinogenesis ,Toxicity ,biology.protein ,Female ,medicine.symptom ,Biomarkers ,Toxicant - Abstract
The aim of this study was to ascertain the long-term effects of Vepacide, a neem-based pesticide on biochemical profiles. Albino Wistar rats were treated orally with 80 (low), 160 (medium) and 320 mg/kg (high) doses of Vepacide in coconut oil for 90 days. Control rats received the same volume of the vehicle. Vepacide caused increase of aspartate and alanine aminotransferase in serum, kidney and lung, and these enzymes decreased in liver in both male and female rats when measured after 45 and 90 days of treatment. The two-way analysis of variance (ANOVA) showed that the alterations in these enzymes were dose–and time-dependent. Sexual dimorphism was observed when male rats were compared with female rats (Student t-test at P< 0.05). Positive correlation was observed with regard to these enzymes between serum, kidney and lung, whereas in the case of serum and liver, a negative correlation was recorded. These enzyme profiles elucidate that they increased in serum with simultaneous decrease in liver, indicating necrosis of liver, whereas in other tissues, the level of enzymes increased, showing an adaptive mechanism due to the chemical stress. The affected enzymes were recovered to normal conditions after 28 days of post-treatment (withdrawal study). Due to the Vepacide treatment, lung was more affected followed by liver and kidney. This study has indicated that these enzymes could be useful as biomarkers for the insult of any toxicant. Besides, they can also help in predictive toxicology.
- Published
- 2001
46. Preliminary studies on the hypoglycaemic effect ofAbroma augusta in alloxan diabetic rats
- Author
-
Halim Eshrat, Mala Rao, M. Ali Hussain, and Kaiser Jamil
- Subjects
Aqueous extract ,Ldl cholesterol ,medicine.medical_specialty ,biology ,business.industry ,Clinical Biochemistry ,biology.organism_classification ,medicine.disease ,chemistry.chemical_compound ,Endocrinology ,chemistry ,Dry weight ,Internal medicine ,Alloxan ,Diabetes mellitus ,Diabetes Mellitus ,medicine ,Abroma augusta ,business - Abstract
The hypoglycemic effect of the aqueous extract ofAbroma augusta (Family: Steculiceae) was studied in normal as well as alloxan diabetic rats. Treatement of diabetic rats with 4 ml (4gm dry weight) of agueous extract ofA. augusta for 16 weeks resulted in gradual but significant fall in fasting blood glucose and improvement in glucose tolerance. Serum total and LDL cholesterol and triacylglycerol which increased in diabetic rats showed improvement. These results show that the water extract ofA. augusta has both hypoglycemic and hypocholesterolemic effects.
- Published
- 2001
47. Isolation of TNT tolerant pseudomonas species (Strain KA) from TNT contaminated soil biotransformation of TNT
- Author
-
Avinash M. Tope and Kaiser Jamil
- Subjects
Chromatography ,biology ,Strain (chemistry) ,Chemistry ,Mechanical Engineering ,General Chemical Engineering ,Biomedical Engineering ,Environmental engineering ,General Physics and Astronomy ,musculoskeletal system ,biology.organism_classification ,Thin-layer chromatography ,Computer Science Applications ,chemistry.chemical_compound ,Biotransformation ,Ammonium ,Gas chromatography ,Electrical and Electronic Engineering ,Microbial biodegradation ,Bacteria ,Transformation efficiency - Abstract
"A 2,4,6-trinitrotoluene (TNT) utilising bacterium, Pseudomonas species (strain KA) was isolated from soils of a munitions processing unit and studied for itsability to grow and metabolise TNT. The result indicated that the isolate could grow aerobically in a minimal salt medium containing 0.25 mM/l TNT at 30 °C. It could completely transform 0.25 mM/l TNT in 5 days giving 2-isomeric monoaminodinitrotoluenes, namely 4-aminodinitrotoluene and 2-aminodinitrotoluene. Products of TNT transformation were analysed and confirmed by thin layer chromatography and gas chromatography coupled with mass spectrometry. Both, growth of the isolate and biotransformation rates were better supported on sugar and ammonium salt when added to the medium separately. Pseudomonas species (strain KA) showed maximum TNT transformation efficiency in the presence of mannose. For degradation of TNT, this strain can be employed to initiate the process in association with the other microbial members that can collectively degrade TNT .
- Published
- 2001
48. Sequence-structure based phylogeny of GPCR Class A Rhodopsin receptors
- Author
-
Kavita Kumari Kakarala and Kaiser Jamil
- Subjects
Likelihood Functions ,Rhodopsin ,Class C GPCR ,Sequence Analysis, DNA ,Biology ,Neuropeptide Y receptor ,Receptors, G-Protein-Coupled ,Evolution, Molecular ,Biochemistry ,Genetics ,biology.protein ,GPR18 ,Animals ,Humans ,Homology modeling ,Galanin ,Receptor ,Molecular Biology ,Ecology, Evolution, Behavior and Systematics ,Phylogeny ,G protein-coupled receptor - Abstract
Current methods of G protein coupled receptors (GPCRs) phylogenetic classification are sequence based and therefore inappropriate for highly divergent sequences, sharing low sequence identity. In this study, sequence structure profile based alignment generated by PROMALS3D was used to understand the GPCR Class A Rhodopsin superfamily evolution using the MEGA 5 software. Phylogenetic analysis included a combination of Neighbor-Joining method and Maximum Likelihood method, with 1000 bootstrap replicates. Our study was able to identify potential ligand association for Class A Orphans and putative/unclassified Class A receptors with no cognate ligand information: GPR21 and GPR52 with fatty acids; GPR75 with Neuropeptide Y; GPR82, GPR18, GPR141 with N-arachidonylglycine; GPR176 with Free fatty acids, GPR10 with Tachykinin & Neuropeptide Y; GPR85 with ATP, ADP & UDP glucose; GPR151 with Galanin; GPR153 and GPR162 with Adrenalin, Noradrenalin; GPR146, GPR139, GPR142 with Neuromedin, Ghrelin, Neuromedin U-25 & Thyrotropin-releasing hormone; GPR171 with ATP, ADP & UDP Glucose; GPR88, GPR135, GPR161, GPR101with 11-cis-retinal; GPR83 with Tackykinin; GPR148 with Prostanoids, GPR109b, GPR81, GPR31with ATP & UTP and GPR150 with GnRH I & GnRHII. Furthermore, we suggest that this study would prove useful in re-classification of receptors, selecting templates for homology modeling and identifying ligands which may show cross reactivity with other GPCRs as signaling via multiple ligands play a significant role in disease modulation.
- Published
- 2013
49. The codon 399 Arg/Gln XRCC1 polymorphism is associated with lung cancer in Indians
- Author
-
Umamaheshwar Rao Naidu Madireddy, Kirmani Natukula, Usha Rani Pingali, Venkata Satya Suresh Attili, and Kaiser Jamil
- Subjects
Male ,Cancer Research ,Lung Neoplasms ,Genotype ,Epidemiology ,DNA repair ,Glutamine ,non-small cell lung cancer (NSCLC) ,India ,Biology ,Adenocarcinoma ,Arginine ,Polymerase Chain Reaction ,XRCC1 ,Risk Factors ,Carcinoma, Non-Small-Cell Lung ,medicine ,Humans ,Genetic Predisposition to Disease ,Lung cancer ,Codon ,Genotyping ,Neoplasm Staging ,Genetics ,Polymorphism, Genetic ,Public Health, Environmental and Occupational Health ,Base excision repair ,DNA ,Middle Aged ,medicine.disease ,Prognosis ,DNA-Binding Proteins ,Survival Rate ,X-ray Repair Cross Complementing Protein 1 ,Oncology ,Case-Control Studies ,Carcinoma, Squamous Cell ,Female ,Restriction fragment length polymorphism ,Polymorphism, Restriction Fragment Length ,Follow-Up Studies - Abstract
Background: The XRCC1 (X-ray repair cross complimenting group-I) gene in BER (base excision repair) pathway is essential for DNA repair process. Polymorphisms in this gene are associated with variations in the repair efficiency which might predispose individuals to development of various cancers. Two variants of XRCC1gene (at codon 399), Gln/Gln and Arg/Gln, have been shown to be related to lowered DNA repair capacity and increased genomic instability in multiple studies. Hence our investigation focused on genotyping these variants to correlate with other multiple risk factors in lung cancer (NSCLC) patients since we hypothesized that these variants of the XRCC1 gene might influence disease susceptibility. Materials and Methods: We examined the frequency of the polymorphism in one hundred cases and an almost equal number of controls after recording their demographics with a structured questionnaire. Genomic DNA from blood samples was extracted for PCR studies, followed by RFLP to determine the variants. The significance of the data was statistically analyzed. Results: The three genotypes in cases and controls were Arg/Arg (40% and 54.45%); Gln/Gln (19% and 9.90%), and Arg/Gln (41.0% and 35.64%) respectively. Among these 3 genotypes, we found Gln/Gln and Arg/Gln to show association with lung cancer. Correlating these genotypes with several parameters, we also found that these two variants were associated with risk in males (p
- Published
- 2013
50. Subacute effects of a phosphorothionate pesticide on mixed function oxidases of wistar rats
- Author
-
Mohammed Mahboob, Kaiser Jamil, and M.K.J. Siddiqui
- Subjects
Male ,Insecticides ,Cytochrome ,Administration, Oral ,Pharmacology ,Kidney ,Cerebro ,Mixed Function Oxygenases ,Cytochrome P-450 Enzyme System ,Cytochrome b5 ,medicine ,Animals ,Sulfhydryl Compounds ,Rats, Wistar ,Lung ,Analysis of Variance ,Oxidase test ,Dose-Response Relationship, Drug ,biology ,Brain ,Cytochrome P450 ,Organothiophosphorus Compounds ,General Medicine ,Pollution ,Rats ,medicine.anatomical_structure ,Liver ,Biochemistry ,Monocrotophos ,Toxicity ,biology.protein ,Food Science - Abstract
Subacute oral toxicity of a newly developed phosphorothionate insecticide (2‐butenoic acid‐3‐(diethoxy‐phosphinothioyl) methyl ester), coded as RPR‐2, was studied in male rats by oral (multiple) intubation of low (0.014 mg kg‐1 day‐1), medium (0.028 mg kg‐1 day‐1), and high (0.042 mg kg‐1 day‐1) dose for 90 days. The medium and high dose produced toxic symptoms along‐with some mortality (20%) occurred in the high dose treated rats. The medium and high doses caused significant inhibition in cytochrome P‐450 activity in liver, lung, kidney and brain tissues at 45 and 90 days. The high dose caused significant decrease in cyt.b5 activity of all the four tissues at 45 and 90 days. Whereas, medium dose brought such effect in liver and lung at 45 and 90 days. Kidney and brain cyt.b5 activity decreased significantly at 90th day due to medium dose. Low dose also caused inhibition in cyt.b5 activity in brain at 90th day. Cytochrome P‐450 reductase activity was decreased significantly in liver, lung, kidney...
- Published
- 2000
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