RNA-Binding Protein CELF1 Controls MARCKS mRA Translation in Oral Cancer Cells

Post-transcriptional gene regulation plays an important role in controlling gene expression patterns in mammalian cells. CUG-binding and Embryonic Lethal vision-type RNA-binding protein 3 (ETR)-like Factor (CELF1), also known as CUGBP1, is a RNA-binding protein involved in post-transcriptional gene regulation through nuclear (alternative splicing) and cytoplasmic (mRNA turnover and translation) mRNA processing events. Primarily, CELF1 is known for its contribution to the development of myotonic dystrophy (DM1). But, published observations from our laboratory and others determined that CELF1 is overexpressed in head and neck squamous cell carcinoma (HNSCC) as well as multiple other cancers. Unpublished proteomic pulsed-stable isotope labeling by amino acids in cell culture (pSILAC) from our laboratory, has identified approximately putative 1350 CELF1 target proteins were controlled at the mRNA translation level in UM74B oral cancer cells. The pSILAC data and subsequent ribosome profiling validation experiments revealed that the protein expression of MARCKS (Myrisoylated alanine-rich kinase C substrate) is significantly reduced upon CELF1 knockdown in comparison to control oral cancer cells. MARCKS is known to play an important role in cell shape, cell motility, secretion, transmembrane transport, and regulation of the cell cycle in cancer cells. We have determined that MARKCS protein is overexpressed in HNSCC cell lines compared to primary normal oral keratinocytes. Moreover, CELF1 directly controls the expression of MARCKS, but its mRNA levels remain unchanged in oral cancer cells. CELF1 ribonucleoprotien immunoprecipitation (RNP-IP) experiments determined that MARCKS mRNA is directly associated with CELF1. The cell migratory role of MARCKS was evaluated by a scratch wound healing assay and transwell migration assay. Depletion of CELF1 and MARCKS independently resulted in reduction of cell migration. Moreover, overexpression of CELF1 in normal non-malignant human oral keratinocyte cells resulted in overexpression of MARCKS and enhanced cell migration. Finally, shRNA-mediated reduction of CELF1 in association with exogenously expressed MARCKS in oral cancer cells, we were able to rescue the CELF1-mediated cell migration phenotype. In conclusion, our results demonstrate that CELF1 controls cell migration through regulating MARCKS protein translation in oral cancer cells

ROLE OF CRM IN ERP ESPECIALLY FOR SELECTED ENGINEERING COMPANIES IN AHMEDABAD.

The purpose of this investigation is to identify the awareness of CRM in ERP and essential components of CRM-ERP integration and how it deals with HR concerns. CRM: The Business Focus factor and information quality of ERP solution, system quality of ERP solution, system use of ERP solution and appropriateness of ERP solutions in context to Engineering companies of Ahmedabad City. The total CRM-ERP integration oriented Engineering companies are 58 in Ahmedabad. The selection of 15 companies is made possible on the basis of five zones of Ahmedabad City. The source of data is primary and secondary. The primary data are collected through structured questionnaire administered to the respondents in person and through email; scale reliability test and Pearson correlations test are conducted as statistical tests for achieving the objectives

Treatment of severe falciparum malaria: quinine versus artesunate

Background: Malaria is the most important disease of human being. More than 40% of the world’s population is considered to be at risk of exposure of this disease. Malaria  infection  has  been  increasing  over  recent  years  due  to combination  of  factors  including  increasing  resistance  of  malarial  parasite. Most of the strains of  P. falciparum  are  now  resistance  to  conventional  drugs  like chloroquine  in  many areas. The  objective of this study was to compare  the  efficacy and safety  of quinine  and  artesunate  in  treatment  of  P. falciparum  malaria.Methods: This  is  hospital  based  prospective  study, conducted  amongst  35 randomly  selected  patients  of  severe  P. falciparum  malaria. Patients  with  any contraindications  of  either  drug  were  excluded  to  avoid  bias. Standard statistical tests were applied for qualitative as well as quantitative data.Results: As  per  the  study  end  point  results  of  difference  of  mortality  in patients  receiving  either  drug  was  not  significant (p > 0.75), but  difference  in clinical  parameters  like  fever  clearance  time (p <0.01), parasite  clearance  time (p < 0.001) and  coma  resolution  time (p < 0.001)  were  significant  among  patients receiving  artesunate. There  were  no  any  significant  differences  in  adverse  effects of  both  the  drugs. Mortality was same in both arms taking either drug.Conclusions: Artesunate  is  as  good  as  quinine  in  mortality  aspect  but artesunate  is  superior  in fever clearance time (FCT) &  parasite clearance time (PCT). Coma resolution time is faster with quinine as compared to artesunate. There are no significant adverse effects of either drug. So  artesunate  is  equivalent  or  superior  for  treatment  for  severe  falciparum malaria

Identification of chalcone derivatives as putative non-steroidal aromatase inhibitors potentially useful against breast cancer by molecular docking and ADME prediction

Aromatase is an influential target to overcome estrogen receptor positive breast cancer, as the enzyme is responsible for conversion of androstenedione to estrone, a promising drug target for therapeutic management of breast cancer. Chalcones are prominent biosynthetic compounds and parent candidate for the synthesis of heterocycles with diversified biological activities. The prime objective of the present study is to evaluate the binding interaction of 2-hydroxyphenyl- prop-2-en-1-one (1A-1X), 2-hydroxy-4-methoxyphenyl- prop-2-en-1-one (3A-3X), 2,4-dihydroxyphenyl- prop-2-en-1-one (9A-9X) and 1-hydroxynaphthalen-2-yl-prop-2-en-1-one (5A-5X) derivatives with aromatase enzyme by molecular docking study and also check their ADME properties by maestro suit. The designed chalcones derivatives have been docked against our target protein with PDB id 3S7S retrieved from the protein data bank, whereas exemestane has been taken as the positive control. As docking data revealed that docking score of 1K, 1U, 1B 3K 3N, 5K, 5U, 9S, 9K, 9N and 9F compounds found less than exemestane and all of these compounds with appropriate ADME properties have proven their excellent absorption as well as solubility characteristics. The present findings provided valuable information about binding interactions of chalcones derivatives to the active site of aromatase. These compounds may serve as potential lead compound for developing new aromatase inhibitors in breast cancer treatment

Identification of chalcone derivatives as putative non-steroidal aromatase inhibitors potentially useful against breast cancer by molecular docking and ADME prediction

283-293Aromatase is an influential target to overcome estrogen receptor positive breast cancer, as the enzyme is responsible for conversion of androstenedione to estrone, a promising drug target for therapeutic management of breast cancer. Chalcones are prominent biosynthetic compounds and parent candidate for the synthesis of heterocycles with diversified biological activities. The prime objective of the present study is to evaluate the binding interaction of 2-hydroxyphenyl- prop-2-en-1-one (1A-1X), 2-hydroxy-4-methoxyphenyl- prop-2-en-1-one (3A-3X), 2,4-dihydroxyphenyl- prop-2-en-1-one (9A-9X) and 1-hydroxynaphthalen-2-yl-prop-2-en-1-one (5A-5X) derivatives with aromatase enzyme by molecular docking study and also check their ADME properties by maestro suit. The designed chalcones derivatives have been docked against our target protein with PDB id 3S7S retrieved from the protein data bank, whereas exemestane has been taken as the positive control. As docking data revealed that docking score of 1K, 1U, 1B 3K 3N, 5K, 5U, 9S, 9K, 9N and 9F compounds found less than exemestane and all of these compounds with appropriate ADME properties have proven their excellent absorption as well as solubility characteristics. The present findings provided valuable information about binding interactions of chalcones derivatives to the active site of aromatase. These compounds may serve as potential lead compound for developing new aromatase inhibitors in breast cancer treatment

Emergency Medical Services Capacity for Prehospital Care of Stroke Patients in North Carolina

An acute stroke requires immediate medical attention. Emergency medical services (EMS) can positively impact acute stroke patients through early identification and expedited transport to specialized acute care facilities. However, EMS systems are not equally qualified and prepared to respond to, evaluate, and manage stroke patients in a timely manner. The aims of this dissertation were twofold. First, the capacity of EMS systems in North Carolina (NC) for prehospital stroke care was assessed. Education of EMS personnel on stroke should continue to be an area of focus, particularly the frequency and content of trainings. Significant progress has been made in prehospital stroke care in NC, specifically with the use of standardized patient care protocols, validated scales and screening tools, destination plans, and advance notification policies. However, improvements in the use of stroke destination plans and communication of stroke screen results remain to be realized. Overall deficiencies in EMS stroke care capacity were observed regardless of system patient volume and population density. Secondly, prehospital time intervals for EMS responses to patients suspected of having a stroke were evaluated. While national consensus guidelines recommend EMS responds to a stroke patient in 9 minutes and spends no more than 15 minutes at the scene before transport, almost half of suspected stroke events took longer than recommended in NC in 2009-2010. EMS units that responded with lights and sirens were associated with shorter time intervals, suggesting that a greater sense of urgency leads to expedited responses. Furthermore, EMS systems that included specific instructions in their stroke protocols to limit scene time were associated with significantly shorter time units spent at the scene with a suspected stroke patient. Prehospital stroke care requires continuous monitoring and quality improvement efforts at the system and personnel levels. This dissertation identified areas of system capacity in need of improvement and evaluated predictors of prehospital delays in NC. Other regions in the United States could similarly assess their stroke experiences using these tools. Finally, further study of the impact of EMS stroke care on emergency department and hospital processes are warranted.Doctor of Philosoph

DEVELOPMENT AND VALIDATION OF A HIGH-PERFORMANCE THIN-LAYER CHROMATOGRAPHY FOR THE DETERMINATION OF TERBUTALINE SULFATE, BROMHEXINE HYDROCHLORIDE, AND ETOPHYLLINE IN PHARMACEUTICAL DOSAGE FORM

Objective: The study aimed to development and validation of simple, precise, and reliable high-performance thin-layer chromatography (HPTLC) for the determination of terbutaline sulfate (TBS), bromhexine hydrochloride (BRH), and etophylline (ETP) in pharmaceutical dosage form. Methods: A simple, precise, rapid, and accurate HPTLC method was developed for the estimation of TBS, BRH, and ETP in pharmaceutical dosage form. Pre-coated silica gel G60 F254 aluminum sheet (10 cm2×10 cm2 and thickness 0.2 mm) was used as stationary phase while mobile phase consisting of benzene: methanol:glacial acetic acid 8:0.5:1.5 v/v/v detection at 275 nm. The present method had validated according to ICH guidelines. Results: Migration distance found 80 mm at 275 nm. The retention factor found to be 0.24, 0.57, and 0.68, respectively. The detector response was linear in the concentration range of 60–210 ng/band, 2400–8400 ng/band, and 96–336 ng/band, respectively. The linear regression equation being Y=32.20x−562.9, Y=11.79x−1711, and Y=1.756x−5636, respectively. The limit of detection for TBS 0.677 μg, for BRH 8.123 μg, and for ETP 57.915 μg and limit of quantification to be 2.053, 24.617, and 175.5 μg, respectively, were found. The developed method validated by ICH guideline, i.e., accuracy, precision, robustness, specificity, and system suitability. Conclusion: In this study, we had developed a simple, fast, and reliable HPTLC method for the determination of TBS, BRH, and ETP in pharmaceutical dosage form

Design, Synthesis, Molecular Docking, and Antibacterial Evaluation of Some Novel Flouroquinolone Derivatives as Potent Antibacterial Agent

Objective. Quinolone moiety is an important class of nitrogen containing heterocycles widely used as key building blocks for medicinal agents. It exhibits a wide spectrum of pharmacophores and has bactericidal, antiviral, antimalarial, and anticancer activities. In view of the reported antimicrobial activity of various fluoroquinolones, the importance of the C-7 substituents is that they exhibit potent antimicrobial activities. Our objective was to synthesize newer quinolone analogues with increasing bulk at C-7 position of the main 6-fluoroquinolone scaffold to produce the target compounds which have potent antimicrobial activity. Methods. A novel series of 1-ethyl-6-fluoro-4-oxo-7-{4-[2-(4-substituted phenyl)-2-(substituted)-ethyl]-1-piperazinyl}-1,4-dihydroquinoline-3-carboxylic acid derivatives were synthesized. To understand the interaction of binding sites with bacterial protein receptor, the docking study was performed using topoisomerase II DNA gyrase enzymes (PDB ID: 2XCT) by Schrodinger’s Maestro program. In vitro antibacterial activity of the synthesized compounds was studied and the MIC value was calculated by the broth dilution method. Results. Among all the synthesized compounds, some compounds showed potent antimicrobial activity. The compound 8g exhibited good antibacterial activity. Conclusion. This investigation identified the potent antibacterial agents against certain infections

Study of Thermal Properties on UV-Curable Coatings Derived from Oleochemical Polyols

Abstract: Over the last few years, UV radiation curing has become a well established coating technology used for several different applications. Polymeric component based on renewable resource is another area for getting low VOC coatings. In the present study cellulose and soya fatty acid were used to prepare oleochemical polyols which in turn reacted with diisocyanates to get PU which is further reacted with hydroxyl terminated acrylates to get oligomeric urethane acrylates. These polymeric compounds are used without any organic solvent for UV-coating formulation and cured by UV light on the metal surfaces. Thus effect of different types of polyols were used to prepared UV coatings studied on thermal properties like dynamic mechanical properties (DMA) and thermogravimetric analysis (TGA