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| 1 | Biotin biosynthesis in Mycobacterium tuberculosis: physiology, biochemistry and molecular intervention显示文摘Biotin is an important micronutrient that serves as an essential enzyme cofactor.Bacteria obtain biotin either through de novo synthesis or by active uptake from exogenous sources.Mycobacteria are unusual amongst bacteria in that their primary source of biotin is through de novo synthesis.Here we review the importance of biotin biosynthesis in the lifecycle of Mycobacteria.Genetic screens designed to identify key metabolic processes have highlighted a role for the biotin biosynthesis in bacilli growth,infection and survival during the latency phase.These studies help to establish the biotin biosynthetic pathway as a potential drug target for new anti-tuberculosis agents. | Wanisa Salaemae Al Azhar Grant W.Booker Steven W.Polyak | 2011 | Protein & Cell2011,2,9: | 3 |
| 2 | Free fatty acids receptors 2 and 3 control cell proliferation by regulating cellular glucose uptake显示文摘BACKGROUND Colorectal cancer(CRC)is a worldwide problem,which has been associated with changes in diet and lifestyle pattern.As a result of colonic fermentation of dietary fibres,short chain free fatty acids are generated which activate free fatty acid receptors(FFAR)2 and 3.FFAR2 and FFAR3 genes are abundantly expressed in colonic epithelium and play an important role in the metabolic homeostasis of colonic epithelial cells.Earlier studies point to the involvement of FFAR2 in colorectal carcinogenesis.AIM To understand the role of short chain FFARs in CRC.METHODS Transcriptome analysis console software was used to analyse microarray data from CRC patients and cell lines.We employed short-hairpin RNA mediated down regulation of FFAR2 and FFAR3 genes,which was validated using quantitative real time polymerase chain reaction.Assays for glucose uptake and cyclic adenosine monophosphate(cAMP)generation was done along with immunofluorescence studies to study the effects of FFAR2/FFAR3 knockdown.For measuring cell proliferation,we employed real time electrical impedancebased assay available from xCELLigence.RESULTS Microarray data analysis of CRC patient samples showed a significant down regulation of FFAR2 gene expression.This prompted us to study the FFAR2 in CRC.Since,FFAR3 shares significant structural and functional homology with FFAR2,we knocked down both these receptors in CRC cell line HCT 116.These modified cell lines exhibited higher proliferation rate and were found to have increased glucose uptake as well as increased level of glucose transporter 1.Since,FFAR2 and FFAR3 signal through G protein subunit(Gαi),knockdown of these receptors was associated with increased cAMP.Inhibition of protein kinase A(PKA)did not alter the growth and proliferation of these cells indicating a mechanism independent of cAMP/PKA pathway.CONCLUSION Our results suggest role of FFAR2/FFAR3 genes in increased proliferation of colon cancer cells via enhanced glucose uptake and exclude the role of PKA mediated cAMP signalling.Alternate pathways could be involved that would ultimately result in increased cell proliferation as a result of down regulated FFAR2/FFAR3 genes.This study paves the way to understand the mechanism of action of short chain FFARs in CRC. | Saeed Al Mahri Amal Al Ghamdi Maaged Akiel Monira Al Aujan Sameer Mohammad Mohammad Azhar Aziz | 2020 | World Journal of Gastrointestinal Oncology2020,12,5: | 2 |
| 3 | A New Rank Test Nonparametric Procedure for Radar Detection in Multiple Target Situations显示文摘This paper deals with the detection performance evaluation of a new nonparametric procedure. The test statistics of the proposed processor have a simple statistical form which is derived from that of the suboptimum rank test procedure [1]. The performance of the new distributionfree detection technique is obtained through Monte-Carlo simulations and compared with that of the suboptimum scheme when detecting nonfluctuating target embedded in Gaussian noise and in the presence of interfering target returns among the reference samples. The new nonparametric detector is shown to give a relative improvement over the suboptimum processor, especially, when the background environment contains a numerous-number of extraneous targets. | Mohamed B EL Mashade & Abdel Atty Moussa (Electrical Engineering Dept., Faculty of Engineering, Al Azhar Universityt Nasr City, Cairo, Egypt) | 1998 | Journal of Systems Engineering and Electronics1998,9,3: | 1 |
| 4 | Oxidative stress induces DNA fragmentation and caspase activation via the c-Jun NH2-terminal kinase pathway in H9c2 cardiac muscle cells显示文摘 | Turner NA Xia F Azhar G ct al | 1998 | J Mol Cell Cardiol1998,30,: | 1 |
| 5 | Tocilizumab in severe COVID-19-A randomized,double-blind,placebo-controlled trial显示文摘Background:The therapeutic effectiveness of interleukin-6 receptor inhibitor in critically ill hospitalized patients with coronavirus disease 2019(COVID-19)is uncertain.Methods:To evaluate the efficacy and safety of the outcome as recovery or death of tocilizumab for severe acute respiratory syndrome-coronavirus-2(SARS-CoV-2)infection,we conducted a randomized,double-blinded,placebo-controlled phase 2 trial in critically ill COVID-19 adult patients.The patients were randomly assigned in a 4:1 ratio to receive standard medical treatment plus the recommended dose of either tocilizumab or the placebo drug.Randomization was stratified.The primary outcome was the recovery or death after administration of tocilizumab or a placebo drug.The secondary outcomes were clinical recovery or worsening of the patients’symptoms and inflammatory markers and discharge from the hospital.Results:Of 190 patients included in this study,152 received tocilizumab,and 38 received a placebo.The duration of hospital stay of the interventional group was 12.9±9.2,while the placebo group had a more extended hospital stay(15.6±8.8).The mortality ratio for the primary outcome,ie,mortality or recovery in the tocilizumab group was 17.8%;p=0.58 by log-rank test).The mortality ratio in the placebo group was 76.3%;p=0.32 by log-rank test).The inflammatory markers in the tocilizumab group significantly declined by day 16 compared to the placebo group.Conclusions:The use of tocilizumab was associated with decreased mortality,earlier improvement of inflamma-tory markers,and reduced hospital stay in patients with severe COVID-19. | Muhammad Irfan Malik Sardar Al Fareed Zafar Fabiha Qayyum Muna Malik Muhammad Sohaib Asghar Muhammad Junaid Tahir Ammarah Arshad Fatima Khalil Hafiza Shafia Naz Mudassar Aslam Jodat Saleem Abdul Aziz Mustafa Usman Azhar Muhammad Naqash Zohaib Yousaf | 2022 | Infectious Medicine2022,1,2: | 0 |