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Harnessing the potential of gene editing technology using CRISPR in inflammatory bowel disease

World Journal of Gastroenterology 2019年第18期25卷 2177-2187页

作者： Viktor Limanskiy arpita Vyas Lakshmi Shankar Chaturvedi Dinesh Vyas Department of Surgery San Joaquin General Hospital College of Medicine CNSU College of Medicine and College of Pharmacy California Northstate University

The molecular scalpel of clustered regularly interspersed short palindromic repeats/CRISPR associated protein 9(CRISPR/Cas9) technology may be sharp enough to begin cutting the genes implicated in inflammatory bowel disease(IBD) and consequently decrease the 6.3 billion dollar annual financial healthcare burden in the treatment of IBD. For the past few years CRISPR technology has drastically revolutionized DNA engineering and biomedical research field. We are beginning to see its application in gene manipulation of sickle cell disease,human immunodeficiency virus resistant embryologic twin gene modification and IBD genes such as Gatm(Glycine amidinotransferase, mitochondrial),nucleotide-binding oligomerization domain-containing protein 2, KRT12 and other genes implicated in adaptive immune convergence pathways have been subjected to gene editing, however there are very few publications. Furthermore,since Crohn's disease and ulcerative colitis have shared disease susceptibility and share genetic gene profile, it is paramount and is more advantageous to use CRISPR technology to maximize impact. Although, currently CRISPR does have its limitations due to limited number of specific Cas enzymes, off-target activity,protospacer adjacent motifs and crossfire between different target sites. However,these limitations have given researchers further insight on how to augment and manipulate enzymes to enable precise gene excision and limit crossfire between target sites.

关键词： Clustered regularly interspersed short palindromic repeats Inflammatory bowel disease Crohn’s disease Ulcerative colitis Gene excision Gene editing Gene therapy Financial impact of inflammatory bowel disease on healthcare Clustered regularly interspersed short palindromic repeats crossfire

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Light signaling and UV-B-mediated plant growth regulation^FA

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Journal of Integrative Plant Biology 2020年第9期62卷 1270-1292页

作者： arpita Yadav Deeksha Singh Maneesh Lingwan Premachandran Yadukrishnan Shyam Kumar Masakapalli Sourav Datta Department of Biological Sciences Indian Institute of Science Education and Research(IISER)BhopalBhopalMadhya Pradesh462066India School of Basic Sciences Indian Institute of Technology(IIT)MandiKamandHimachal Pradesh175005India

Light plays an important role in plants' growth and development throughout their life cycle. Plants alter their morphological features in response to light cues of varying intensity and quality. Dedicated photoreceptors help plants to perceive light signals of different wave-lengths. Activated photoreceptors stimulate the down-stream signaling cascades that lead to extensive gene expression changes responsible for physiological and developmental responses. Proteins such as ELONGATED HYPOCOTYL5 (HY5) and CONSTITUTIVELY PHOTO-MORPHOGENIC 1 (COP1) act as important factors which modulate light-regulated gene expression, especially during seedling development. These factors function as central regulatory intermediates not only in red, far-red, and blue light pathways but also in the UV-B signaling pathway. UV-B radiation makes up only a minor fraction of sunlight, yet it imparts many positive and negative effects on plant growth. Studies on UV-B perception, signaling, and response in plants has considerably surged in recent times. Plants have developed different strat-egies to use UV-B as a developmental cue as well as to withstand high doses of UV-B radiation. Plants' re-sponses to UV-B are an integration of its cross-talks with both environmental factors and phytohormones. This review outlines the current developments in light sig-naling with a major focus on UV-B-mediated plant growth regulation.

关键词： plant Plants seedling

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Acute oedema associated with risperidone use:a report

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General Psychiatry 2020年第4期33卷 247-248页

作者： arpita Thakur Vijay Niranjan Pali Rastogi Ramghulam Razdan Department of Psychiatry Mahatma Gandhi Memorial Medical CollegeIndoreMadhya PradeshIndia Department of Psychiatry MGM Medical College IndoreIndoreMadhya PradeshIndia

Risperidone acts by potent serotonergic,dopaminergic and alpha adrenergic receptor *** most common side effects reported are extrapyramidal symptoms,dizziness,sedation,insomnia,headache,anxiety,nausea,constipation and weight *** associated with risperidone use is a rare side *** we present a report on pedal oedema associated with use of oral risperidone 4 mg per day for acute-onset psychotic *** this case report we want to make clinicians aware about this important side effect as it can affect patients*compliance and quality of life.

关键词： edema effect. acute

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Hepatoprotective potential of ethanolic extract of Ziziphus oenoplia(L.)Mill roots against antitubercular drugs induced hepatotoxicity in experimental models

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Asian Pacific Journal of Tropical Medicine 2012年第4期5卷 283-288页

作者： Ch V Rao AKS Rawat Anil P Singh arpita Singh Neeraj Verma Pharmacognosy and Ethnopharmacology Division National Botanical Research Institute(Council of Scientific and Industrial Research)Rana Pratap MargP.O.Box No.436Lucknow 226001Uttar PradeshIndia Department of Pharmacology Goel Institute of Pharmacy & SciencesFaizabad Road(Near Indira Canal) Lucknow 227105Uttar PradeshIndia

Objective:To evaluate the hepatoprotective potential of ethanolic(50%) extract of Ziziphus oenoplia(L.) Mill(***) root against isoniazid(INH) and rifampicin(RIF) induced liver damage in animal ***:Five groups of six rats each were selected for the *** extract at a dose of 150 and 300 mg/kg as well as silymarin(100 mg/kg) were administered orally once daily for 21 d in INH + RIF treated *** serum levels of glutamic oxaloacetic transaminase(SGOT),glutamate pyruvate transaminase(SGPT),alkaline phosphatase (SALP),and bilirubin were estimated along with activities of superoxide dismutase,catalase, glutathione S-transferase,glutathione peroxidase,and hepatic melondialdehyde formation. Histopathological analysis was carried out to assess injury to the ***:The considerably elevated serum enzymatic activities of glutamic oxaloacetic transaminase,glutamate pyruvate transaminase,alkaline phosphatase and bilirubin due to INH + RIF treatment were restored towards norma) in a dose dependent manner after the treatment with ethanolic extract of *** ***,the decreased activities of superoxide dismutase,catalase, glutathione S-transferase and glutathione peroxidase were also restored towards normal dose *** addition,ethanolic extract also significantly prevented the elevation of hepatic melondialdehyde formation in the liver of INH + RIF intoxicated rats in a dose dependent manner. The biochemical observations were supplemented with histopathological examination of rat liver ***:The results of this study slrongly indicate that ethanolic extract of *** has a potent hepatoprotective action against INH + RIF induced hepatic damage in rats.

关键词： Ziziphus oenoplia(Rhamnaceae) Rifampicin Isoniazid Hepatotoxicity

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Mutation in angiotensin II type 1 receptor disrupts its binding to angiotensin II leading to hypotension： An insight into hydrogen bonding patterns

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Frontiers of physics 2012年第5期7卷 477-484页

作者： arpita KUNDU Sudha RAMAIAH Anand ANBARASU Medical & Biological Computing Laboratory School of Biosciences and Technology VIT University Vellore-632014 Tamil Nadu India

To understand the role of angiotensin II type 1 receptor gene （AGTR1） gene products in relation to hypotension we have analyzed the single nucleotide polymorphisms （SNPs） associated with this gene. This can help us to understand the genetic variations that can alter the function of the gene products. In this present study, we report the polymorphic variant associated with AGTR1 and its weak interaction with angiotensin II （AngII） which leads to hypotension. Out of 1318 SNPs, six are found to be non-synonymous, of which rs1064533 shows significant damaging effect. A missense mutation （T1255G）, i.e., from thymine to guanine for rs1064533 in AGTR1 gene results in amino acid substitution from cysteine （Cys） to tryptophan （Trp） in the receptor protein. A strong hydrogen bond exists between Cys289 of native AGTR1 protein and glutamine 167 of AngII. Interestingly, it is replaced by a weak hydrogen bond in the mutant protein between Trp289 （mutant residue） and serine 340. Such a substitution from small, hydrophilic to bulky, hydrophobic residue in AGTR1 protein results in reduced binding affinity of the receptor protein with AngII, leading to hypotension. The results presented from this in silico study will open up new prospect for genetic analysis of AGTR1 gene and will be beneficial to the researchers for understanding the role played by AGTR1 gene in hypotension disease.

关键词： AGTR1 AnglI hypotension rs1064533 cysteine tryptophan

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Analysis of phytochemical profile of Terminalia arjuna bark extract with antioxidative and antimicrobial properties

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Asian Pacific Journal of Tropical Biomedicine 2013年第12期3卷 960-966页

作者： Shreya Mandal arpita Patra Animesh Samanta Suchismita Roy arpita Mandal Tapasi Das Mahapatra Shrabani Pradhan Koushik Das Dilip Kumar Nandi Department of Nutrition Microbiology and Human PhysiologyRaja N L Khan Women's College

Objective:To investigate phytochemical screening,antimicrobial activity and qualitative thin layer chromatographic separation of flavonoid components,antioxidant activity and total flavonoid compound of Terminalia ***:For phytochemical screening,some common and available standard tests were *** bioassay was done through agar well diffusion *** of antioxidant activity and flavonoid compounds were done through thin layer *** antioxidant activity was measured by 2,2-diphenyl-1-picrylhydrazyl(DPPH)in colorimetric *** chloride colorimetric method was used for total flavonoid ***:Phytochemical screening showed the active compounds presence in high concentration,such as phytosterol,lactones,flavonoids,phenolic compounds and tannins and *** anlimicrobial activity of extract showed that greater inhibition zone against Gram negative bacteria than Gram positive *** methanolic extract showed a promising antioxidant activity,as absorption of DPPH redicles decreased in DPPH free radical scavenging *** components having antioxidant property present in the methanol extract at a level of199.00 mg quercetin equivalent/g of dried methanol extract in colorimetric ***:The Terminalia arjuna bark extract revealed the presence of bio-active constituents which are known to exhibit medicinal as well as physiological activities.

关键词： Terminalia arjuna Phytocompound TLC Antioxidant Total flavonoid Antimicrobial activity DPPH

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The actin cytoskeleton coordinates the signal transduction and antigen processing functions of the B cell antigen receptor

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Frontiers in Biology 2013年第5期8卷 475-485页

作者： Chaohong LIU Margaret K. FALLEN Heather MILLER arpita UPADHYAYA Wenxia SONG Department of Cell Biology & Molecular Genetics University of Maryland College Park MD 20742 USA Department of Physics University of Maryland College Park MD 20742 USA Division of Immunology Children's Hospital of Chongqing Medical University Chongqing 400014 China

The B cell antigen receptor （BCR） is the sensor on the B cell surface that surveys foreign molecules （antigen） in our bodies and activates B cells to generate antibody responses upon encountering cognate antigen. The binding of antigen to the BCR induces signaling cascades in the cytoplasm, which provides the first signal for B cell activation. Subsequently, BCRs internalize and target bound antigen to endosomes, where antigen is processed into T cell recognizable forms. T helper cells generate the second activation signal upon binding to antigen presented by B cells. The optimal activation of B cells requires both signals, thereby depending on the coordination of BCR signaling and antigen transport functions. Antigen binding to the BCR also induces rapid remodeling of the cortical actin network of B cells. While being initiated and controlled by BCR signaling, recent studies reveal that this actin remodeling is critical for both the signaling and antigen processing functions of the BCR, indicating a role for actin in coordinating these two pathways. Here we will review previous and recent studies on actin reorganization during BCR activation and BCR- mediated antigen processing, and discuss how actin remodeling translates BCR signaling into rapid antigen uptake and processing while providing positive and negative feedback to BCR signaling.

关键词： actin cytoskeleton endocytosis signal transduction receptor

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Finding neoepitopes in mouse models of personalized cancer immunotherapy

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Frontiers in Biology 2016年第5期11卷 366-375页

作者： Sahar Al Seesi Alok Das Mohapatra arpita Pawashe Ion I. Mandoiu Fei Duan Department of Immunology and Carole and Ray Neag Comprehensive Cancer Center University of Connecticut Cancer Center Farmington CT 06030 USA Department of Computer Science & Engineering University of Connecticut Storrs CT 06269 USA

BACKGROUND： Cancer immunotherapy uses one＇s own immune system to fight cancerous cells. As immune system is hard- wired to distinguish self and non-self, cancer immunotherapy is predicted to target cancerous cells specifically, therefore is less toxic than chemotherapy and radiation therapy, two major treatments for cancer. Cancer immunologists have spent decades to search for the specific targets in cancerous cells. METHODS： Due to the recent advances in high throughput sequencing and bioinformatics, evidence has merged that the neoantigens in cancerous cells are probably the cancer-specific targets that lead to the destruction of cancer. We will review the transplantable murine tumor models for cancer immunotherapy and the bioinformatics tools used to navigate mouse genome to identify tumor-rejecting neoantigens. RESULTS： Several groups have independently identified point mutations that can be recognized by T cells of host immune system. It is consistent with the note that the formation ofpeptide-MHC I-TCR complex is critical to activate T cells. Both anchor residue and TCR-facing residue mutations have been reported. While TCR-facing residue mutations may directly activate specific T cells, anchor residue mutations improve the binding of peptides to MHC I molecules, which increases the presentation of peptides and the T cell activation indirectly. CONCLUSIONS： Our work indicates that the affinity of neoepitopes for MHC I is not a predictor for anti-tumor immune responses in mice. Instead differential agretopic index （DAI）, the numerical difference of epitope-MHC I affinities between the mutated and un-mutated sequences is a significant predictor. A similar bioinformatics pipeline has been developed to generate personalized vaccines to treat human ovarian cancer in a Phase I clinical trial.

关键词： cancer immunotherapy tumor antigens neoantigens neoepitopes differential agretopic index (DAI) RNA-Seq single nucleotide variant (SNV)

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A novel vague set approach for selective contrast enhancement of mammograms using multiresolution

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Journal of Biomedical Science and Engineering 2009年第8期2卷 575-581页

作者： arpita Das Mahua Bhattacharya Institute of Radio Physics & Electronics University of Calcutta Kolkata India

The proposed algorithm introduces a novel vague set approach to develop a selective but robust, flexible and intelligent contrast enhancement technique for mammograms. Wavelet based filtering analysis can produce Low Frequency (LF) and High Frequency (HF) subbands of the original input images. The extremely small size microcalcifications become visible under multiresolution techniques. LF subband is then fuzzified by conventional fuzzy c-means clustering (FCM) algorithm with justified number of clusters. HF components, representing the narrow protrusions and other fine details are also fuzzified by FCM with justified number of clusters. Vague set approach captures the hesitancies and uncertainties of truly affected masses/other breast abnormalities with normal glandular tissues. After highlighting the masses/microcalcifications accurately, both LF and HF subbands are transformed back to the original resolution by inverse wavelet transform. The results show that the proposed method can successfully enhance the selected regions of mammograms and provide better contrast images for visual interpretation.

关键词： Multiresolution Vague Set Approach True- membership Functions False-Membership Functions

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p38γand p38δas biomarkers in the interplay of colon cancer and inflammatory bowel diseases

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Cancer Communications 2022年第9期42卷 897-901页

作者： Pilar Fajardo Maria Taskova Miguel A.Martín-Serrano Jonas Hansen Sofie Slott Anna K.Jakobsen Marie-Louise Wibom Beñat Salegi Alberto Muñoz Antonio Barbachano arpita Sharma John Mark Gubatan Aida Habtezion Juan J.Sanz-Ezquerro Kira Astakhova Ana Cuenda Department of Immunology and Oncology National Centre of Biotechnology/Consejo Superior de Investigaciones CientíficasDarwin 3Madrid 28049Spain PhD Programme in Molecular Bioscience Doctoral SchoolUniversidad Autónoma de MadridMadrid 28049Spain Department of Chemistry Technical University of Denmark2800 Kongens LyngbyDenmark Adolphe Merkle Institute University of FribourgChemin des Verdiers 41700 FribourgSwitzerland Stanford School of Medicine StanfordCA 94305USA Instituto de Investigaciones Biomédicas“Alberto Sols” Consejo Superior de Investigaciones CientíficasUniversidad Autónoma de MadridMadrid 28029Spain Centro de Investigación Biomédica en Red-Cáncer Instituto de Salud Carlos IIIMadrid 28029Spain Instituto de Investigación Sanitaria del Hospital Universitario La Paz Madrid 28029Spain Department of Medicine Division of Gastroenterology and HepatologyStanford University School of MedicineStanfordCA 94305USA Department of Molecular and Cellular Biology Centro Nacional de Biotecnología/Consejo Superior de Investigaciones CientíficasDarwin 3Madrid 28049Spain

Dear Editor,Colorectal cancer(CRC)is the second leading cause of cancer death according to the World Health *** with inflammatory bowel disease(IBD),ulcerative colitis(UC)or Crohn’s disease(CD)are at increased risk of developing colitis-associated CRC(CAC)[1];however,our understanding of the inflammationcancer interplay at the molecular level is still limited.

关键词： inflammatory death p38 CRC

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