Publications by authors named "Abdul Arif Khan"

38 Publications

Infection: Their potential implication in the Etiology of Cervical Cancer.

J Cancer 2021 11;12(16):4891-4900. Epub 2021 Jun 11.

Department of Biosciences, Shri Ram Group of College (SRGC), Muzaffarnagar 251001, India.

Pathogenic bacterial strains can alter the normal function of cells and induce different levels of inflammatory responses that are connected to the development of different diseases, such as tuberculosis, diarrhea, cancer etc. () is an intracellular obligate gram-negative bacterium which has been connected with the cervical cancer etiology. Nevertheless, establishment of causality and the underlying mechanisms of carcinogenesis of cervical cancer associated with remain unclear. Studies reveal the existence of in cervical cancer patients. The DNA repair pathways including mismatch repair, nucleotide excision, and base excision are vital in the abatement of accumulated mutations that can direct to the process of carcinogenesis. recruits DDR proteins away from sites of DNA damage and, in this way, impedes the DDR Therefore, by disturbing host cell-cycle control, chromatin and DDR repair, makes a situation favorable for malignant transformation. Inflammation originated due to infection directs over production of reactive oxygen species (ROS) and consequent oxidative DNA damage. This review may aid our current understanding of the etiology of cervical cancer in -infected patients.
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http://dx.doi.org/10.7150/jca.58582DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8247366PMC
June 2021

Exploring polyps to colon carcinoma voyage: can blocking the crossroad halt the sequence?

Authors:
Abdul Arif Khan

J Cancer Res Clin Oncol 2021 Aug 11;147(8):2199-2207. Epub 2021 Jun 11.

Division of Microbiology, Indian Council of Medical Research-National AIDS Research Institute, Pune, Maharashtra, India.

Colorectal cancer is an important public health concern leading to significant cancer associate mortality. A vast majority of colon cancer arises from polyp which later follows adenoma, adenocarcinoma, and carcinoma sequence. This whole process takes several years to complete and recent genomic and proteomic technologies are identifying several targets involved in each step of polyp to carcinoma transformation in a large number of studies. Current text presents interaction network of targets involved in polyp to carcinoma transformation. In addition, important targets involved in each step according to network biological parameters are also presented. The functional overrepresentation analysis of each step targets and common top biological processes and pathways involved in carcinoma indicate several insights about this whole mechanism. Interaction networks indicate TP53, AKT1, GAPDH, INS, EGFR, and ALB as the most important targets commonly involved in polyp to carcinoma sequence. Though several important pathways are known to be involved in CRC, the central common involvement of PI3K-AKT indicates its potential for devising CRC management strategies. The common and central targets and pathways involved in polyp to carcinoma progression can shed light on its mechanism and potential management strategies. The data-driven approach aims to add valuable inputs to the mechanism of the years-long polyp-carcinoma sequence.
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http://dx.doi.org/10.1007/s00432-021-03685-5DOI Listing
August 2021

Immune mediating molecules and pathogenesis of COVID-19-associated neurological disease.

Microb Pathog 2021 Jun 4;158:105023. Epub 2021 Jun 4.

Department of Biochemistry, ICMR-National JALMA Institute for Leprosy and Other Mycobacterial Diseases, Agra, 282001, India.

Background: Long period of SARS-CoV-2 infection has been associated with psychiatric and cognitive disorders in adolescents and children. SARS-CoV-2 remains dormant in the CNS leading to neurological complications. The wide expression of ACE2 in the brain raises concern for its involvement in SARS-CoV-2 infection. Though, the mechanistic insights about blood-brain barriers (BBB) crossing by SARS-CoV-2 and further brain infection are still not clear. Moreover, the mechanism behind dormant SARS-CoV-2 infections leading to chronic neurological disorders needs to be unveiled. There is an urgent need to find out the risk factor involved in COVID-19-associated neurological disease. Therefore, the role of immune-associated genes in the pathogenesis of COVID-19 associated neurological diseases is presented which could contribute to finding associated genetic risk factors.

Method: The search utilizing multiple databases, specifically, EMBASE, PubMed (Medline), and Google Scholar was performed. Moreover, the literature survey on the involvement of COVID-19, neuropathogenesis, and its consequences was done.

Description: Persistent inflammatory stimuli may promote the progression of neurodegenerative diseases. An increased expression level of cytokine, chemokine, and decreased expression level of immune cells has been associated with the COVID-19 patient. Cytokine storm was observed in severe COVID-19 patients. The nature of SARS-CoV-2 infection can be neuroinflammatory. Genes of immune response could be associated with neurodegenerative diseases.

Conclusion: The present review will provide a useful framework and help in understanding COVID-19-associated neuropathogenesis. Experimental studies on immune-associated genes in COVID-19 patients with neurological manifestations could be helpful to establish its neuropathogenesis.
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http://dx.doi.org/10.1016/j.micpath.2021.105023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8177310PMC
June 2021

Salmonella enterica subsp. enterica host-pathogen interactions and their implications in gallbladder cancer.

Microb Pathog 2021 Aug 29;157:105011. Epub 2021 May 29.

Department of Molecular and Human Genetics, Jiwaji University, Gwalior, MP, 474001, India.

Background: Several studies have linked chronic typhoid infection with gallbladder carcinoma without completely understood mechanism. This study was performed in order to understand role of Salmonella in gallbladder cancer etiology.

Methods: Known Salmonella host-pathogen interactions were screened from database in addition to known gallbladder carcinoma targets. Host-pathogen interaction map of S. enterica was prepared and screened for interactions with gallbladder carcinoma targets. Further functional overrepresentation analysis was performed to understand the role of human targets involved in Salmonella host-pathogen interactions in gallbladder carcinoma.

Results: Salmonella interact with several human proteins involved in gallbladder carcinoma. MAPK and RAC1 are the most important human proteins based on node degree value among all GBC associated interactors identified in current data search. Functional over-representation analysis reveals that Salmonella can induce adenocarcinoma which constitutes 85% of gallbladder cancer.

Conclusion: Though, the role of MAPK/ERK and PI3K/AKT/mTOR pathway is already suggested for Salmonella mediated gallbladder cancer, but current data based approach indicate several new insight for exploration of the role of Salmonella in gallbladder cancer etiology. The results indicate about several other processes including CREB/SP-1 and BSG(CD147) signaling, that must be given consideration for understanding the role of Salmonella in gallbladder cancer.
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http://dx.doi.org/10.1016/j.micpath.2021.105011DOI Listing
August 2021

ACE2 and TMPRSS2 polymorphisms in various diseases with special reference to its impact on COVID-19 disease.

Microb Pathog 2021 Jan 2;150:104621. Epub 2020 Dec 2.

Division of Microbiology, ICMR-National AIDS Research Institute, Pune, 411026, India.

Background: A carboxypeptidase protein called ACE2 is found in many organs. ACE2 protein can play a pivotal role to regulate the pathological changes of several diseases including COVID-19. TMPRSS2 gene is expressed in many human tissues and plays a critical role in spreading the infection of the viruses including coronavirus and progression of prostate cancer, and hence could be used as a potential drug target. There are limited reports on occurrence of genetic polymorphism of ACE2 and TMPRSS2 in general population, expressions in pathological conditions, and its impact on COVID-19 disease. Hence we comprehended the occurrence of ACE2, TMPRSS2 polymorphism in general population, expression in various diseases and its impact on COVID-19 disease.

Method: We utilized multiple databases, PubMed (Medline), EMBASE and Google Scholar for literature search.

Description: ACE2 polymorphisms have significant linkages with various diseases, including severity of SARS-CoV-2 infection. Genetic variations of these genes contribute to individual's genetic susceptibility to viral infection and its subsequent clearance. The diversity and variations in the population distribution of these genes, might greatly influence and in turn reflect into the observed population and gender differences of the severity and clinical outcomes of SARS-CoV-2 infection.

Conclusion: There are diversities in distribution of ACE2 and TMPRSS2 polymorphisms among different populations. Analyzing the genetic variants and expression of ACE2 and TMPRSS2 genes, in a population may provide the genetic marker for susceptibility or resistance against the coronavirus infection, which might be useful for identifying the susceptible population groups for targeted interventions and for making relevant public health policy decisions.
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http://dx.doi.org/10.1016/j.micpath.2020.104621DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7709597PMC
January 2021

Bacterial nucleomodulins and cancer: An unresolved enigma.

Transl Oncol 2021 Jan 1;14(1):100922. Epub 2020 Nov 1.

Department of Biomedical Sciences, Cedars-Sinai Medical Center, Davis Bldg. Rm. 2008, 8700 Beverly Blvd. Los Angeles, CA 90048, United States.

Recent studies in microbial pathogenesis have identified several bacterial proteins with the potential to influence host cell nuclei. This field of research is in its infancy, however it is rapidly growing. In particular, the role of bacterial nucleomodulins in animal oncogenesis is an area that requires attention. Earlier research has suggested the role of nucleomodulins in plant tumor development and these findings may provide us with a better understanding of the role of these proteins in human cancer development. This proposition is further supported by previous identification of nucleomodulins present in bacteria that have been associated with cancer development, but their role in human cancer is unclear. In this article, we provide an update on the status of these nucleomodulins and their role in cancer etiology. We collected information about known bacterial nucleomodulins and tried to relate their mechanistic implication with already known plant tumor development model. The present research indicates that bacterial nucleomodulins may be an important target in cancer etiology and knowledge of their role in human oncogenesis may help us to create suitable alternative cancer management strategies.
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http://dx.doi.org/10.1016/j.tranon.2020.100922DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7644672PMC
January 2021

System biological investigations of hydroxychloroquine and azithromycin targets and their implications in QT interval prolongation.

Chem Biol Interact 2020 Dec 22;332:109299. Epub 2020 Oct 22.

Department of Biomedical Sciences, Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Davis Bldg. Rm. 2014 8700 Beverly Blvd. Los Angeles, CA, 90048, USA.

COVID-2019 pandemic is affecting people worldwide in the absence of an effective treatment strategy. Several suggestive therapeutic options through drug repurposing are recommended, but a complete consensus is not reached. A combination of Hydroxychloroquine (HCQ) and Azithromycin (AZM) has been widely tried and discussed but its administration has also led to potential adversities in patients. Studies are suggesting that most prominent adverse event with HCQ and AZM combination is QT interval prolongation. We studied interaction of HCQ with AZM and subsequent effect of this drug combination on QT interval prolongation. We performed system biological investigation of HCQ and AZM targets and screened important targets and pathways possibly involved in QT interval prolongation. The best core hub protein drug targets involved in QT interval prolongation were identified as HSP90AA1 exclusively associated with HCQ, while AKT1 exclusively associated with AZM on the basis of node degree value. It was found that PI3K/Akt, VEGF, ERBB2 pathways must be given consideration for understanding the role of HCQ and AZM in QT interval prolongation. Conclusion: Computational methods have certain limitations based on source database coverage and prediction algorithms and therefore this data needs experimental correlation to draw final conclusion, but current findings screen targets for QT interval prolongation associated with HCQ and AZM. These proteins and pathways may provide ways to reduce this major risk associated with this combination.
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http://dx.doi.org/10.1016/j.cbi.2020.109299DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7578186PMC
December 2020

Current status of probiotics for prevention and management of gastrointestinal cancers.

Expert Opin Biol Ther 2021 Mar 9;21(3):413-422. Epub 2020 Oct 9.

Department of Biomedical Sciences, Pathology and Laboratory Medicine, Cedars- Sinai Medical Centre, Los Angeles, USA.

Introduction: Gastrointestinal cancers contribute to a significant number of cancer- associated mortality. The gastrointestinal tract harbors a multitude of microorganisms, known as the microbiota. Recently, the microbiota is considered to be an accessory organ resulting in several health benefits. The microbiota is involved in almost all aspects of an individual ranging from managing behavior to controlling metabolism, immune status and the response to a disease. Researchers are observing the modulation of microbiota in almost every disease, including cancer. Probiotics are microorganisms that can help to alter the host microbiota toward a healthy state thus providing benefits from many diseases including cancer.

Areas Covered: We explored the current status of the use of probiotics in cancer patients. Although probiotic bacteria can provide significant benefits to individuals suffering from cancer, the number of cancer-specific clinical products containing probiotics is not comparable to research studies showing their benefits. The lack of available products is due to several factors including a lack of risk assessment data of beneficial probiotics in cancer patients.

Expert Opinion: Laboratory investigations indicate a huge potential of probiotics for the prevention and management of gastrointestinal cancer, but more clinical studies are required to support their application in clinical settings.
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http://dx.doi.org/10.1080/14712598.2021.1828858DOI Listing
March 2021

Comparative host-pathogen protein-protein interaction analysis of recent coronavirus outbreaks and important host targets identification.

Brief Bioinform 2021 03;22(2):1206-1214

Department of Biomedical Sciences, Department of Pathology and Laboratory Medicine.

Last two decades have witnessed several global infectious outbreaks. Among these, coronavirus is identified as a prime culprit ranging from its involvement in severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS) to COVID-19. These infections involved in huge healthcare and economic cost incurred globally. Every time, coronavirus improved its infection ability and surprised the medical practitioners and researchers. Currently, COVID-19 is also causing numerous infections and stalled global activities. Global efforts are underway to identify potential viral targets for management of these outbreaks, but significant progress in prevention of these outbreaks is not yet achieved. We explored host-pathogen protein-protein interactions of MERS, SARS and COVID-19, and identified host targets common among all recent coronavirus outbreaks. Further, we tried to understand their potential for management of coronavirus. The common proteins involved in coronavirus host-pathogen interactions indicate their indispensable role in the pathogenesis and therefore targeting these proteins can give strategies to prevent current and future coronavirus outbreaks. Viral variability necessitates development of new therapeutic modalities for every outbreak, in contrast targeting necessary human proteins required by all coronaviruses can provide us a clue to prevent current and future coronavirus outbreaks. We found that targeting FURIN and TMPRSS2 can provide good results due to their common involvement in current and previous outbreaks. We also listed some known molecules against these two targets for their potential drug repurposing evaluation. Although, several recent studies undergoing with targeting these proteins for management of coronavirus, but safety evaluation and risk assessment must be given prime importance while targeting human proteins.
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http://dx.doi.org/10.1093/bib/bbaa207DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7546044PMC
March 2021

Neurological and cognitive significance of probiotics: a holy grail deciding individual personality.

Future Microbiol 2020 07 5;15:1059-1074. Epub 2020 Aug 5.

Department of Microbiology, Government College University Faisalabad, Pakistan.

The role of the human microbiome in the brain and behavioral development is an area of increasing attention. Recent investigations have found that diverse mechanisms and signals including the immune, endocrine and neural associations are responsible for the communication between gut microbiota and the brain. The studies have suggested that alteration of intestinal microbiota using probiotic formulations may offer a significant role in the maturation and organization of the brain and can shape the brain and behavior as well as mood and cognition in human subjects. The understanding of the possible impact of gut microflora on neurological function is a promising phenomenon that can surely transform the neurosciences and may decipher the novel etiologies for neurodegenerative and psychiatric disorders.
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http://dx.doi.org/10.2217/fmb-2019-0143DOI Listing
July 2020

Protein-protein interactions of HPV--human and their potential in cervical cancer.

Future Microbiol 2020 05 1;15:509-520. Epub 2020 Jun 1.

Department of Biomedical Sciences, Cedars-Sinai Medical Center, 8700 Baverly Blvd., Los Angeles, CA 90048, USA.

HPV is an important cause of cervical cancer, but (CT) is suspiciously involved in this disease ranging from direct to its involvement as a cofactor with HPV. We performed this study to understand the interaction of HPV and  with humans and its contribution to cervical cancer. Host-pathogen and pathogen-pathogen protein-protein interaction maps of HPV/CT/human were prepared and compared to analyze interactions during single/coinfection of and HPV. The interacting human proteins were detected by their involvement in cervical cancer. may interact with several cancer associated proteins while HPV and  largely interact with different human proteins, suggesting different pathogenesis.  coinfection with HPV may modulate cervical cancer development.
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http://dx.doi.org/10.2217/fmb-2019-0242DOI Listing
May 2020

COVID-2019-associated overexpressed Prevotella proteins mediated host-pathogen interactions and their role in coronavirus outbreak.

Bioinformatics 2020 Jul;36(13):4065-4069

Department of Pathology and Laboratory Medicine.

Motivation: The outbreak of COVID-2019 initiated at Wuhan, China has become a global threat by rapid transmission and severe fatalities. Recent studies have uncovered whole genome sequence of SARS-CoV-2 (causing COVID-2019). In addition, lung metagenomic studies on infected patients revealed overrepresented Prevotella spp. producing certain proteins in abundance. We performed host-pathogen protein-protein interaction analysis between SARS-CoV-2 and overrepresented Prevotella proteins with human proteome. We also performed functional overrepresentation analysis of interacting proteins to understand their role in COVID-2019 severity.

Results: It was found that overexpressed Prevotella proteins can promote viral infection. As per the results, Prevotella proteins, but not viral proteins, are involved in multiple interactions with NF-kB, which is involved in increasing clinical severity of COVID-2019. Prevotella may have role in COVID-2019 outbreak and should be given importance for understanding disease mechanisms and improving treatment outcomes.

Supplementary Information: Supplementary data are available at Bioinformatics online.
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http://dx.doi.org/10.1093/bioinformatics/btaa285DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7373214PMC
July 2020

Nanozymes for medical biotechnology and its potential applications in biosensing and nanotherapeutics.

Biotechnol Lett 2020 Mar 16;42(3):357-373. Epub 2020 Jan 16.

Department of Microbiology, Government College University Faisalabad, Faisalabad, Pakistan.

Recent past years have witnessed the development of several artificial enzymes, using different materials to mimic natural enzymes with respect to their structure and functions. The nanozymes are nanomaterials possessing similar characteristics to the natural enzymes and have emerged recently as an innovative class of artificial enzymes. The nanozymes have got remarkable attention from the researchers and notable developments have been achieved owing to their unique properties compared with natural enzymes and classic artificial enzymes. In this regard, several nanomaterials have been scrutinized so far to mimic different natural enzymes for wider applications ranging from imaging, sensing, water treatment, pollutant removal, and therapeutics. The applications of nanozymes in biomedicine research are fast-growing and various nanozymes have been implicated in diagnostic medicine, targeted cancer therapy. Such abilities make them an appropriate alternative for the development of affordable, sustainable and safe diagnostic as well as therapeutic agents.
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http://dx.doi.org/10.1007/s10529-020-02795-3DOI Listing
March 2020

Antifungal efficacy of Itraconazole loaded PLGA-nanoparticles stabilized by vitamin-E TPGS: In vitro and ex vivo studies.

J Microbiol Methods 2019 06 7;161:87-95. Epub 2019 Feb 7.

Nanobiotechnology Unit, Department of Pharmaceutics, College of Pharmacy, King Saud University, P.O. Box: 2457, Riyadh 11451, Saudi Arabia. Electronic address:

Itraconazole (ITZ) loaded Poly-(D, L-lactic-co-glycolic acid, PLGA) nanoparticles (PLGA-NPs) stabilized by D-α-Tocopherol polyethylene-glycol succinate-1000 (TPGS) were developed by nanoprecipitation and single emulsion solvent evaporation methods to improve antifungal activity of ITZ by enhancing its solubility, and hence bioavailability. Encapsulation efficiency, drug loading, in-vitro release, ex-vivo permeation and antifungal activity were performed for the optimized PLGA-NPs. Characterization of PLGA-NPs were performed by scanning electron microscopy, dynamic light scattering, differential scanning calorimetry, Fourier transform infrared spectroscopy, and powder X-ray diffractometry. We observed that nanoprecipitation method was more efficient in encapsulating ITZ by using 0.3% TPGS (stabilizer) than single emulsion solvent evaporation method. Our thermal analysis studies showed no characteristic peaks for crystalline ITZ, indicating drug efficiently encapsulated inside the nanoparticle with no compatibility issues. Drug loaded PLGA-NPs preserved the antifungal activity of ITZ against Candida albicans. Drug release profile from the NPs showed an initial burst release followed by an extended release phase suggesting the potential of NPs for sustained release applications. Furthermore, ITZ encapsulated in PLGA-NPs showed enhanced intestinal permeability in the ex-vivo study. In conclusion, the developed nano-system successfully encapsulated ITZ, yielding an increased permeation and consequential antifungal activity.
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http://dx.doi.org/10.1016/j.mimet.2019.01.020DOI Listing
June 2019

Hepatitis B virus precore G1896A mutation in chronic liver disease patients with HBeAg negative serology from North India.

Saudi J Biol Sci 2018 Nov 10;25(7):1257-1262. Epub 2016 May 10.

Department of Medicine, Maulana Azad Medical College, University of Delhi, New Delhi, India.

Hepatitis B with precore stop codon mutation is related with severe liver damage in HBeAg negative patients. It is of utmost importance to screen the G1896A precore mutation. The study was designed to assess the impact of G1986A mutations in patients with different clinical spectra of the liver disease by PCR-LCR. 210 HBV positive patients with HBeAg negative serology of different kind of liver diseases (AVH = 72, FH = 21, CH = 79, Cirrhosis = 20 and HCC = 18) were screened. Patients were screened for the presence or absence of precore G1896A mutation by PCR-LCR. Direct nucleotide sequencing was done to confirm the results of LCR. Precore mutant in HCC was 94.4% (17/18), 85.7% (18/21) in FH, 60% (12/20) in liver cirrhosis, 48.1% (38/79) in chronic hepatitis and 27.7% (20/72) in AVH cases. The serum ALT level was statistically significant between HBeAg negative WT and G1896A mutants in chronic hepatitis cases. ALT level and HBV DNA level was slightly raised in the pre core mutant but and was not significant. Genotype D had a higher prevalence (79.5%) as compared to genotype A (20.5%). The mutations detected by PCR-LCR were in 100% concordance with direct sequencing. The exceptionally high prevalence of G1896A in FH and HCC demonstrates that the precore mutants are strongly associated with the progression of liver diseases in patients with HBeAg negative serology. The findings are also suggestive of screening HBV precore G1896A mutation particularly in HBeAg negative cases. The precore G1896A mutation increases proportionately in severe form of liver diseases. LCR can be a suitable tool for screening of G1896A mutations.
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http://dx.doi.org/10.1016/j.sjbs.2016.05.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6252005PMC
November 2018

Survivin, a molecular target for therapeutic interventions in squamous cell carcinoma.

Cell Mol Biol Lett 2017 5;22. Epub 2017 Apr 5.

School of Studies in Biotechnology, Jiwaji University, Gwalior, 474001 MP India.

Squamous cell carcinoma (SCC) is the most common cancer worldwide. The treatment of locally advanced disease generally requires various combinations of radiotherapy, surgery, and systemic therapy. Despite aggressive multimodal treatment, most of the patients relapse. Identification of molecules that sustain cancer cell growth and survival has made molecular targeting a feasible therapeutic strategy. Survivin is a member of the Inhibitor of Apoptosis Protein (IAP) family, which is overexpressed in most of the malignancies including SCC and totally absent in most of the normal tissues. This feature makes survivin an ideal target for cancer therapy. It orchestrates several important mechanisms to support cancer cell survival including inhibition of apoptosis and regulation of cell division. Overexpression of survivin in tumors is also associated with poor prognosis, aggressive tumor behavior, resistance to therapy, and high tumor recurrence. Various strategies have been developed to target survivin expression in cancer cells, and their effects on apoptosis induction and tumor growth attenuation have been demonstrated. In this review, we discuss recent advances in therapeutic potential of survivin in cancer treatment.
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http://dx.doi.org/10.1186/s11658-017-0038-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5415770PMC
August 2017

Colorectal cancer-inflammatory bowel disease nexus and felony of Escherichia coli.

Life Sci 2017 Jul 12;180:60-67. Epub 2017 May 12.

Nanomedicine Research Unit, Department of Pharmaceutics, College of Pharmacy, PO Box 2457, King Saud University, Riyadh 11451, Saudi Arabia; King Abdullah Institute for Nanotechnology, King Saud University, PO Box 2455, Riyadh 11451, Saudi Arabia.

Colorectal cancer (CRC) has a multifactorial etiology. Although the exact cause of CRC is still elusive, recent studies have indicated microbial involvement in its etiology. Escherichia coli has emerged as an important factor in CRC development since the bacterium can cause changes in the gut that lead to cancerous transformation. A number of studies indicate that chronic inflammation induced by microorganisms, including E. coli, during inflammatory bowel disease (IBD) predisposes an individual to CRC. The evidence that support the role of E. coli in the etiology of CRC, through IBD, is not limited only to chronic inflammation. The growth of E. coli as an intracellular pathogen during IBD and CRC enable the bacteria to modulate the host cell cycle, induce DNA damage and accumulate mutations. These are some of the contributing factors behind the etiology of CRC. The present article considers the current status of the involvement of E. coli, through IBD, in the etiology of CRC. We discuss how intracellular E. coli infection can cause changes in the gut that can eventually lead to cellular transformation. In addition, the recent management strategies that target E. coli for prevention of CRC are also discussed.
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http://dx.doi.org/10.1016/j.lfs.2017.05.016DOI Listing
July 2017

Non-invasive administration of biodegradable nano-carrier vaccines.

Am J Transl Res 2017 15;9(1):15-35. Epub 2017 Jan 15.

Nanomedicine Research Unit, Department of Pharmaceutics, College of Pharmacy, King Saud UniversityP. O. Box: 2457, Riyadh 11451, Saudi Arabia; King Abdullah Institute for Nanotechnology, King Saud UniversityP. O. Box: 2455, Riyadh 11451, Saudi Arabia.

Polymeric nanoparticulate carriers play an important role and holding a significant potential for the development of novel immunomodulatory agents as easily they are taken up by antigen presenting cells. They allow an enhanced antigen stability, better immunogenicity and immunostimulatory effect with sustained and controlled release of the antigen to the target sites. Better information and vital understanding of mechanism of action, interaction of such vectors with the APCs and dendritic cells and antigen release kinetics in immunomodulatory effects, and improved knowledge of their fate and distribution are now needed, those collectively would speed up the rational strategies of nanoparticles as carriers for vaccines and other protein antigens. The evolution of such innovative adjuvants for protein and DNA immunizations are an exciting and growing zone in immunology, which may enhance the clinical outcomes in many infectious and non-infectious diseases. This review summarizes the recent advances in nano-vaccinology with polymeric (especially biodegradable) carriers, their methods of preparation, surface modification, their interaction with antigen presenting cells, release of antigens, its kinetics and mechanism in the delivery of vaccines via non-invasive routes.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5250701PMC
January 2017

Inter-kingdom prediction certainty evaluation of protein subcellular localization tools: microbial pathogenesis approach for deciphering host microbe interaction.

Brief Bioinform 2018 01;19(1):12-22

Microbial pathogenesis involves several aspects of host-pathogen interactions, including microbial proteins targeting host subcellular compartments and subsequent effects on host physiology. Such studies are supported by experimental data, but recent detection of bacterial proteins localization through computational eukaryotic subcellular protein targeting prediction tools has also come into practice. We evaluated inter-kingdom prediction certainty of these tools. The bacterial proteins experimentally known to target host subcellular compartments were predicted with eukaryotic subcellular targeting prediction tools, and prediction certainty was assessed. The results indicate that these tools alone are not sufficient for inter-kingdom protein targeting prediction. The correct prediction of pathogen's protein subcellular targeting depends on several factors, including presence of localization signal, transmembrane domain and molecular weight, etc., in addition to approach for subcellular targeting prediction. The detection of protein targeting in endomembrane system is comparatively difficult, as the proteins in this location are channelized to different compartments. In addition, the high specificity of training data set also creates low inter-kingdom prediction accuracy. Current data can help to suggest strategy for correct prediction of bacterial protein's subcellular localization in host cell.
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http://dx.doi.org/10.1093/bib/bbw093DOI Listing
January 2018

Antifungal efficacy of amphotericin B encapsulated fibrin microsphere for treating Cryptococcus neoformans infection in Swiss albino mice.

Braz J Infect Dis 2016 Jul-Aug;20(4):342-8. Epub 2016 Jun 11.

King Saud University, College of Pharmacy, Department of Pharmaceutics, Riyadh, Saudi Arabia.

A natural and biocompatible fibrin microsphere is one of the most promising dual delivery vehicle as compared to other traditionally designed delivery modalities. It represents sustained delivery of encapsulated drug and is easily biodegradable in the blood circulation. In the present study, we evaluated the systemic augmentation of the antifungal activity of amphotericin B loaded in fibrin microsphere (AMB-fibrin microsphere) against cryptococcosis in Swiss albino mice. Mice infected with Cryptococcus neoformans were treated with 0.5mg/kg AMB-fibrin microsphere that was given alternately for 7 days. The antifungal potential of AMB-fibrin microsphere was assessed on the basis of reduction of cfu count in the systemic circulation and various vital organs of infected mice. The formulation was found to be highly effective in reducing intracellular pathogen from the experimental animals where fibrin microsphere significantly controlled the release of amphotericin B for longer time duration. The AMB-fibrin microsphere chemotherapy was significantly more effective than free amphotericin B in reducing the fungal burden and showed better survival efficacy (p<0.05). The current study demonstrating the use of novel amphotericin B loaded fibrin microsphere not only imparts protection to the encapsulated amphotericin B but also offers an effective strategy to decrease the drug associated toxicities.
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http://dx.doi.org/10.1016/j.bjid.2016.04.006DOI Listing
March 2017

Optimizing indomethacin-loaded chitosan nanoparticle size, encapsulation, and release using Box-Behnken experimental design.

Int J Biol Macromol 2016 Jun 15;87:329-40. Epub 2016 Feb 15.

Nanomedicine Research Unit, Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia; King Abdullah Institute for Nanotechnology, King Saud University, Riyadh, Saudi Arabia. Electronic address:

Indomethacin chitosan nanoparticles (NPs) were developed by ionotropic gelation and optimized by concentrations of chitosan and tripolyphosphate (TPP) and stirring time by 3-factor 3-level Box-Behnken experimental design. Optimal concentration of chitosan (A) and TPP (B) were found 0.6mg/mL and 0.4mg/mL with 120min stirring time (C), with applied constraints of minimizing particle size (R1) and maximizing encapsulation efficiency (R2) and drug release (R3). Based on obtained 3D response surface plots, factors A, B and C were found to give synergistic effect on R1, while factor A has a negative impact on R2 and R3. Interaction of AB was negative on R1 and R2 but positive on R3. The factor AC was having synergistic effect on R1 and on R3, while the same combination had a negative effect on R2. The interaction BC was positive on the all responses. NPs were found in the size range of 321-675nm with zeta potentials (+25 to +32mV) after 6 months storage. Encapsulation, drug release, and content were in the range of 56-79%, 48-73% and 98-99%, respectively. In vitro drug release data were fitted in different kinetic models and pattern of drug release followed Higuchi-matrix type.
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http://dx.doi.org/10.1016/j.ijbiomac.2016.02.033DOI Listing
June 2016

Systems Biology Approaches for the Prediction of Possible Role of Chlamydia pneumoniae Proteins in the Etiology of Lung Cancer.

PLoS One 2016 12;11(2):e0148530. Epub 2016 Feb 12.

Nanomedicine Research Unit, Department of Pharmaceutics, College of Pharmacy, PO Box 2457, King Saud University, Riyadh 11451, Saudi Arabia.

Accumulating evidence has recently supported the association of bacterial infection with the growth and development of cancers, particularly in organs that are constantly exposed to bacteria such as the lungs, colon, cervical cancer etc. Our in silico study on the proteome of Chlamydia pneumoniae suggests an unprecedented idea of the etiology of lung cancer and have revealed that the infection of C. pneumoniae is associated with lung cancer development and growth. It is reasonable to assume that C. pneumoniae transports its proteins within host-intracellular organelles during infection, where they may work with host-cell proteome. The current study was performed for the prediction of nuclear targeting protein of C. pneumoniae in the host cell using bioinformatics predictors including ExPASy pI/Mw tool, nuclear localization signal (NLS) mapper, balanced sub cellular localization predictor (BaCeILo), and Hum-mPLoc 2.0. We predicted 47/1112 nuclear-targeting proteins of C. pneumoniae connected with several possible alterations in host replication and transcription during intracellular infection. These nuclear-targeting proteins may direct to competitive interactions of host and C. pneumoniae proteins with the availability of same substrate and may be involved as etiological agents in the growth and development of lung cancer. These novel findings are expected to access in better understanding of lung cancer etiology and identifying molecular targets for therapy.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0148530PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4752481PMC
July 2016

Growth inhibition and chemo-radiosensitization of head and neck squamous cell carcinoma (HNSCC) by survivin-siRNA lentivirus.

Radiother Oncol 2016 Feb 30;118(2):359-68. Epub 2015 Dec 30.

School of Studies in Biotechnology, Jiwaji University, Gwalior, India. Electronic address:

Background: Survivin expression is often associated with aggressive tumor behavior and therapy resistance. In this study, we investigated the effect of survivin knockdown by survivin-siRNA lentiviral vector (Svv-Lent) on the response of HNSCC to chemo-radiotherapy, tumor growth and metastasis.

Methods: Four human HNSCC (OSC19, Cal27, Cal33 and FaDu) and one normal HOK cell lines were included in the study, and survivin knockdown was achieved with Svv-Lent treatment. Cell proliferation and apoptosis were measured by MTT and TUNEL assay, respectively. Transwell assays were performed to measure in vitro cell migration and matrigel invasion. Xenograft tumors were developed in nude mice by injecting Cal27 cells subcutaneously and following tail-vein injection of lung and liver metastasis.

Results: Knockdown of survivin significantly suppressed HNSCC cell proliferation and induced apoptosis in vitro. Survivin inhibition could also significantly reduce in vitro cell migration and matrigel invasion that might be due to inactivation of matrix metalloproteinases. In vivo studies showed significant repression of Cal27 xenograft tumor growth and tissue metastasis leading to improvement in mice survival in the Svv-Lent treated group compared to controls. Our data indicated that survivin expression in HNSCC cells contributed to chemo-radioresistance, and its down-regulation increased anti-cancer effects of paclitaxel, cisplatin and radiation.

Conclusions: Our findings suggest that sustained survivin expression facilitates HNSCC tumor growth and confers resistance to chemo-radiotherapy. Svv-Lent therapy may be able to enhance the cytotoxic effect of commonly used anticancer drugs such as cisplatin and paclitaxel, and radiotherapy that could provide a promising strategy for the effective control of resistant head and neck cancer.
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http://dx.doi.org/10.1016/j.radonc.2015.12.007DOI Listing
February 2016

In vitro evaluation of anticancer and antibacterial activities of cobalt oxide nanoparticles.

J Biol Inorg Chem 2015 Dec 12;20(8):1319-26. Epub 2015 Nov 12.

Department of Surgery, Al-Faisal University Riyadh, Riyadh, 11451, Saudi Arabia.

Cobalt oxide nanoparticles (Co3O4-NPs) were synthesized using simple urea-based thermal decomposition method. Phase purity and particle size of as-synthesized nanoparticles were characterized through X-ray diffraction pattern (XRD) and transmission electron microscopy. Through XRD morphology of the Co3O4-NPs was found to be variable in size with range of 36 nm. In our present study, we explored the potential cytotoxic and antibacterial effects of Co3O4-NPs in human colorectal types of cancerous cells (HT29 and SW620) and also nine Gram-positive and Gram-negative bacteria. Co3O4-NPs showed promising anticancer activity against HT29 and SW620 cells with IC50 value of 2.26 and 394.5 μg/mL, respectively. However, no significant effect of Co3O4-NPs was observed against bacterial strains. Furthermore, a detailed study has been carried out to investigate the possible mechanism of cell death in HT29 cancer cell line through the analysis of expression level of anti-apoptotic Bcl2 and BclxL markers. Western blot analysis results suggested significant role of Co3O4-NPs exposure in cell death due to apoptosis.
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http://dx.doi.org/10.1007/s00775-015-1310-2DOI Listing
December 2015

Bacterial munch for infants: potential pediatric therapeutic interventions of probiotics.

Future Microbiol 2015 30;10(11):1881-95. Epub 2015 Oct 30.

Department of Microbiology, Government College University, Faisalabad, Pakistan.

Probiotics are viable microorganisms with the capacity to alter the gastrointestinal microbiota of the host. The recent scientific advancements and development of probiotic formulations have rekindled the importance of these clinical interpretations, underlining the starring role of the gut flora in host metabolism, defense and immune regulation. Despite encouraging preliminary results from randomized clinical trials of probiotics for various clinical conditions including irritable bowel syndrome, necrotizing enterocolitis, gastroenteritis, antibiotic-associated diarrhea, infantile colic, and improvement of digestion and immune function, further evidence is needed to determine the reproducibility of the findings and elucidate the underlying mechanisms. In this review, we have considered the postnatal development of gut flora and appraised the role of probiotics in health and disease condition among infants.
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http://dx.doi.org/10.2217/fmb.15.102DOI Listing
September 2016

Characteristics and Antibiotic Resistance of Urinary Tract Pathogens Isolated From Punjab, Pakistan.

Jundishapur J Microbiol 2015 Jul 25;8(7):e19272. Epub 2015 Jul 25.

Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.

Background: Urinary tract infection (UTI) is deemed the most prevalent infectious disease in that it has now touched the overall incidence of 18/1000 persons per year in the general population.

Objectives: This study sought to determine the characteristics of isolates from patients with UTI and their susceptibility to commonly used antibiotics in Punjab, Pakistan.

Patients And Methods: Totally, 1429 urine samples were analyzed from UTI patients for the isolation of uropathogens at Chughtai's Lahore Lab, Lahore, Pakistan, during a period of 14 months. The antimicrobial susceptibility test was performed via the disc diffusion method for the isolates obtained from 392 (26%) positive cultures.

Results: The highest percentage (67%) of isolates was from females in comparison to males (33%). The frequency of Escherichia coli was the highest (62%) in culture-positive urine samples, followed by E. faecalis (15%), Candida (14%), Pseudomonas (6%), Klebsiella spp. (1%), Proteus (1%), and Staphylococcus aureus (1%). E. coli was highly resistant to antimicrobial drugs, viz. cephalexin (95%), cephradine (95%), pipemidic acid (92%), amikacin (91%), and nalidixic acid (91%). Most of the routine β-lactam antibiotics like amoxicillin/clavulanic acid, ampicillin, and aztreonam were also ineffective against E. coli, with resistance rates of 84%, 84%, and 72%, correspondingly. This pathogen showed maximum susceptibility (97%) against three drugs, namely imipenem, meropenem, and cefoperazone. Piperacillin and fosfomycin also provided significant results against E. coli with respective susceptibility rates of 96% and 90%.

Conclusions: Our results showed that broad-spectrum antibiotics such as imipenem, meropenem, fosfomycin, cefoperazone/sulbactam, and vancomycin would be the first line and the most effective drugs for the empirical treatment of urinary tract pathogens due to their higher resistance rates against other drugs like cephalexin, cephradine, ciprofloxacin, levofloxacin, and norfloxacin.
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http://dx.doi.org/10.5812/jjm.19272v2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4584077PMC
July 2015

Computational prediction of Escherichia coli proteins host subcellular targeting and their implications in colorectal cancer etiology.

Cancer Lett 2015 Aug 24;364(1):25-32. Epub 2015 Apr 24.

Nanomedicine Research Unit, Department of Pharmaceutics, College of Pharmacy, PO Box 2457, King Saud University, Riyadh 11451, Saudi Arabia; King Abdullah Institute for Nanotechnology, King Saud University, P.O.Box 2455, Riyadh 11451, Saudi Arabia.

Recent evidences indicate potential Escherichia coli involvement in colorectal cancer etiology. Colorectal cancer cells are exclusively colonized by enteroinvasive E. coli, which regulates several factors that can affect colorectal cancer progression in susceptible individuals. Earlier, we predicted nuclear targeting of E. coli proteins and their role in colorectal cancer etiology. In this study, we predict targeting of E. coli proteins in host cell mitochondria and cytoplasm and their role in colorectal cancer. Several important biological processes are regulated in the cell cytoplasm and mitochondria, where the targeting of E. coli proteins may have several possible implications. A total of 87/561 and 315/561 E. coli proteins were found to target host cell mitochondria and cytoplasm respectively. These include several proteins with the ability to influence normal growth behavior. The current article provides an outline for E. coli protein targeting in host cells and suggests that these proteins can contribute to the colorectal cancer etiology through a variety of strategies.
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http://dx.doi.org/10.1016/j.canlet.2015.04.024DOI Listing
August 2015

Recent developments in L-asparaginase discovery and its potential as anticancer agent.

Crit Rev Oncol Hematol 2016 Apr 12;100:1-10. Epub 2015 Jan 12.

Department of Biological Sciences, Rani Durgavati University, Jabalpur, MP, India.

L-Asparaginase (EC3.5.1.1) is an enzyme, which is used for treatment of acute lymphoblastic leukaemia (ALL) and other related blood cancers from a long time. This enzyme selectively hydrolyzes the extracellular amino acid L-asparagine into L-aspartate and ammonia, leading to nutritional deficiencies, protein synthesis inhibition, and ultimately death of lymphoblastic cells by apoptosis. Currently, bacterial asparaginases are used for treatment purpose but offers scepticism due to a number of toxicities, including thrombosis, pancreatitis, hyperglycemia, and hepatotoxicity. Resistance towards bacterial asparaginase is another major disadvantage during cancer management. This situation attracted attention of researchers towards alternative sources of L-asparaginase, including plants and fungi. Present article discusses about potential of L-asparaginase as an anticancer agent, its mechanism of action, and adverse effects related to current asparaginase formulations. This article also provides an outlook for recent developments in L-asparaginase discovery from alternative sources and their potential as a less toxic alternative to current formulations.
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http://dx.doi.org/10.1016/j.critrevonc.2015.01.002DOI Listing
April 2016

In silico prediction of escherichia coli proteins targeting the host cell nucleus, with special reference to their role in colon cancer etiology.

Authors:
Abdul Arif Khan

J Comput Biol 2014 Jun 10;21(6):466-75. Epub 2014 Mar 10.

Department of Pharmaceutics, College of Pharmacy, King Saud University , Riyadh, Saudi Arabia .

The potential role of Escherichia coli in the development of colorectal carcinoma (CRC) has been investigated in many studies. Although the exact mechanism is not clear, chronic inflammation caused by E. coli and other related events are suggested as possible causes behind E. coli-induced colon cancer. It has been found that CRC cells, but not normal cells, are colonized by an intracellular form of E. coli. We predicted nuclear targeting of bacterial proteins in the host cell through computational tools nuclear localization signal (NLS) mapper and balanced subcellular localization predictor (BaCeILo). During intracellular E. coli residence, such targeting is highly likely and may have a possible role in colon cancer etiology. We observed that several gene expression-associated proteins of E. coli can migrate to the host nucleus during intracellular infections. This situation provides an opportunity for competitive interaction of host and pathogen proteins with similar cellular substrates, thereby increasing the chances of development of colon cancer. Moreover, the results indicated that proteins localized in the membrane of E. coli mostly act as secretary proteins in host cells. No exact correlation was observed between NLS prediction and nuclear localization prediction by BaCeILo. This is partly because of a number of reasons, including that only 30% of nuclear proteins carry NLS and that proteins <40 kDa molecular weight can passively target the host nucleus. This study concludes that detection of gene expression-specific E. coli proteins and their targeting of the nucleus may have a profound impact on CRC etiology.
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http://dx.doi.org/10.1089/cmb.2014.0001DOI Listing
June 2014

Synthesis and anti-Candidal activity of N-(4-aryl/cyclohexyl)-2-(pyridine-4-yl carbonyl) hydrazinecarbothioamide.

Bioorg Med Chem Lett 2014 Mar 30;24(5):1299-302. Epub 2014 Jan 30.

Stem Cell & Tissue Re-Engineering Program, Research Center, King Faisal Specialized Hospital & Research Center, MBC-03, PO Box 3354, Riyadh 11211, Saudi Arabia.

Eighteen N-(4-aryl/cyclohexyl)-2-(pyridine-4-yl carbonyl) hydrazinecarbothioamide derivatives were synthesized, evaluated against ten clinical isolates of Candida spp. and compared with itraconazole. Introduction of p-chloro (2c), p-iodo (2q), m-chloro (2l) and o-nitro (2r) substitution at phenyl ring of thiosemicarbazide enhanced the anti-Candida activity. Compound (2c) bearing p-cholorophenyl ring was found to be the most effective against Candida albicans ATCC 66027, Candida spp. 12810 (blood) and Candida spp. 178 (HVS) with MIC value of 0.09-0.78 μg/mL, whereas itraconazole exhibits the inhibitory activity with MIC value of 0.04-1.56 μg/mL against all tested strains. There is a correlation between anti-Candidal activity and p-chloro substitution at phenyl ring of thiosemicarbazide. All synthesized compounds were investigated for their potential cytotoxicity against non cancer cell line MCF-10A. The active compounds 2c, 2r and 2a were further investigated for their cytotoxic effects on three cancer cell lines; HT1080 (skin), HepG2 (liver) and A549 (lung). The active compounds showed minimal cytotoxic activity against non cancer cell line and all three cancer cell lines. Moreover, compound 2c displaying better activity against C. albicans ATCC66027 and Candida spp. [blood] compared to reference drug (itraconazole), represents a good lead for the development of newer, potent and broad spectrum anti-Candidal agents.
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http://dx.doi.org/10.1016/j.bmcl.2014.01.060DOI Listing
March 2014
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