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Current and emerging therapeutic approaches for colorectal cancer:A comprehensive review

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World Journal of Gastrointestinal Surgery 2023年第4期15卷 495-519页

作者： Anil Kumar Vipasha Gautam arushi Sandhu Kajal Rawat Antika Sharma Lekha Saha Department of Pharmacology Post Graduate Institute of Medical Education and ResearchChandigarh 160012India

Colorectal cancer(CRC)affects 1 in 23 males and 1 in 25 females,making it the third most common cancer.With roughly 608000 deaths worldwide,CRC accounts for 8%of all cancer-related deaths,making it the second most common cause of death due to cancer.Standard and conventional CRC treatments include surgical expurgation for resectable CRC and radiotherapy,chemotherapy,immunotherapy,and their combinational regimen for non-resectable CRC.Despite these tactics,nearly half of patients develop incurable recurring CRC.Cancer cells resist the effects of chemotherapeutic drugs in a variety of ways,including drug inactivation,drug influx and efflux modifications,and ATPbinding cassette transporter overexpression.These constraints necessitate the development of new target-specific therapeutic strategies.Emerging therapeutic approaches,such as targeted immune boosting therapies,non-coding RNA-based therapies,probiotics,natural products,oncolytic viral therapies,and biomarkerdriven therapies,have shown promising results in preclinical and clinical studies.We tethered the entire evolutionary trends in the development of CRC treatments in this review and discussed the potential of new therapies and how they might be used in conjunction with conventional treatments as well as their advantages and drawbacks as future medicines.

关键词： Colorectal cancer Chemotherapy Immunotherapy RNA interference Probiotics Oncolytic viral therapy

Modernising autism spectrum disorder model engineering and treatment via CRISPR-Cas9:A gene reprogramming approach

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World Journal of Clinical Cases 2023年第14期11卷 3114-3127页

作者： arushi Sandhu Anil Kumar Kajal Rawat Vipasha Gautam Antika Sharma Lekha Saha Department of Pharmacology Post Graduate Institute of Medical Education and Research(PGIMER)Chandigarh 0172ChandigarhIndia

A neurological abnormality called autism spectrum disorder(ASD)affects how a person perceives and interacts with others,leading to social interaction and communication issues.Limited and recurring behavioural patterns are another feature of the illness.Multiple mutations throughout development are the source of the neurodevelopmental disorder autism.However,a well-established model and perfect treatment for this spectrum disease has not been discovered.The rising era of the clustered regularly interspaced palindromic repeats(CRISPR)-associated protein 9(Cas9)system can streamline the complexity underlying the pathogenesis of ASD.The CRISPR-Cas9 system is a powerful genetic engineering tool used to edit the genome at the targeted site in a precise manner.The major hurdle in studying ASD is the lack of appropriate animal models presenting the complex symptoms of ASD.Therefore,CRISPR-Cas9 is being used worldwide to mimic the ASD-like pathology in various systems like in vitro cell lines,in vitro 3D organoid models and in vivo animal models.Apart from being used in establishing ASD models,CRISPR-Cas9 can also be used to treat the complexities of ASD.The aim of this review was to summarize and critically analyse the CRISPRCas9-mediated discoveries in the field of ASD.

关键词： Autism spectrum disorder CRISPR-Cas9 Cellular models Organoids Animal models Therapeutic strategies

Emerging use of artificial intelligence in inflammatory bowel disease

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World Journal of Gastroenterology 2020年第44期26卷 6923-6928页

作者： arushi Kohli Erik A Holzwanger Alexander N Levy Department of Internal Medicine Tufts Medical CenterBostonMA 02111United States Division of Gastroenterology and Hepatology Tufts Medical CenterBostonMA 02111United States

Inflammatory bowel disease(IBD)is a complex,immune-mediated gastrointestinal disorder with ill-defined etiology,multifaceted diagnostic criteria,and unpredictable treatment response.Innovations in IBD diagnostics,including developments in genomic sequencing and molecular analytics,have generated tremendous interest in leveraging these large data platforms into clinically meaningful tools.Artificial intelligence,through machine learning facilitates the interpretation of large arrays of data,and may provide insight to improving IBD outcomes.While potential applications of machine learning models are vast,further research is needed to generate standardized models that can be adapted to target IBD populations.

关键词： Artificial intelligence Machine learning Automated diagnostics Colorectal neoplasia screening Multiomic data Predictive models

Pimavanserin for the treatment of psychosis in Alzheimer’s disease: A literature review

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World Journal of Psychiatry 2020年第7期10卷 162-174页

作者： Shilpa Srinivasan Rajesh R Tampi Kripa Balaram arushi Kapoor Department of Neuropsychiatry and Behavioral Science Palmetto Health USC Medical GroupUniversity of South Carolina School of MedicineColumbiaSC 29203United States Department of Psychiatry and Behavioral Sciences Cleveland Clinic Akron GeneralAkronOH 44307United States MD Department of PsychiatryMetroHealthClevelandOH 44109United States Penn Memory Center at the Penn Neuroscience Center Perelman Center for Advanced MedicinePhiladelphiaPA 19104United States

BACKGROUND Alzheimer’s disease(AD)is among the most prevalent forms of dementia in the world and neuropathological studies suggest similar high prevalence of mixed(AD+vascular)dementias.Approximately 25%-50%of individuals with AD develop psychosis sometime during their illness.The presence of psychosis in AD worsens outcomes.Currently there are no United States Food and Drug Administration(FDA)approved medications for the treatment of psychosis in AD.Pimavanserin,a novel atypical antipsychotic medication,was approved by the FDA for the treatment of hallucinations and delusions associated with Parkinson disease psychosis and is currently in clinical trials for the treatment of psychosis in AD.AIM To evaluate the existing literature regarding the use of pimavanserin for treating psychosis among individuals with AD.METHODS A literature review of clinical studies of pimavanserin treatment for psychosis in individuals with AD was performed using the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines.Trials were identified by systematically searching PubMed,MEDLINE,EMBASE,Cochrane Central Register of Controlled Trials,Web of Science,and Scopus through October 2019.The 5-point Jadad scoring system was used to assess the methodologic quality of the randomized placebo-controlled trials.RESULTS A total of 499 citations were retrieved and pooled in EndNote and de-duplicated to 258 citations.This set was uploaded to Covidence for screening.Two separate screeners(Srinivasan S and Tampi RR)evaluated the titles,abstracts,and full text of eligible articles.Of the identified 258 abstracts,98 articles underwent full text review and 2 publications from 1 randomized controlled trial(RCT)were included in the final analysis.The quality of evidence was assessed to be of good methodologic quality,scoring 4 out of 5 using the 5-point Jadad questionnaire with the Jadad Scoring calculation.This systematic review found only one RCT that evaluated the use of pimavanserin for the treatment of psychosis among individu

关键词： Pimavanserin Alzheimer’s disease Psychosis Psychotic disorders Antipsychotic agents

A systematic investigation of secondary phase dissolution in Mg-Sn alloys

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Journal of Magnesium and Alloys 2019年第4期7卷 725-737页

作者： arushi Dev Niladri Naskar Nishant Kumar Ashutosh Jena Manas Paliwal Department of Materials Science and Engineering Indian Institute of TechnologyGandhinagarPalaj CampusGandhinagarGujarat 382355India Seoul Nation University Seoul 08826Republic of Korea

As-cast Mg-Sn alloys(3,6,and 9 wt%Sn)were solution treated at 653,703 and 753 K(380,430 and 480℃)for 1,4,8,12 and 24 h to determine the variation of secondary phase with respect to Sn content,temperature and time.Mg-3 wt%Sn exhibits Mg2Sn dissolution at all solution treatment temperatures whereas Mg-6 and 9 wt%Sn alloy displays Mg2Sn reprecipitation and dissolution depending on the heat treatment temperature.In addition,a combined mathematical model that predicts the secondary phase dissolution and solute redistribution as a function of temperature and time is presented in this work.This model is a significant improvement compared to the previous studies where the dissolution and homogenization processes are considered independently.The effect of grain size and solute mobility upon the dissolution and homogenization kinetics is discussed as well.

关键词： Solution treatment Homogenization Dissolution Mg-Sn alloys

Is Rotational Trauma the Only Relevant Pathogenic Mechanism in Hemorrhagic Retinopathy of Shaken Baby Syndrome?

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Journal of Forensic Science and Medicine 2018年第2期4卷 104-107页

作者： BS arushi Tripathy Stephanie Dean DO Joyce L de Jong Carl J Schmidt Rudy J Castellani Department of Pathology Western Michigan University Homer Stryker MD School of MedicineKalamazoo Office of the Chief Medical Examiner BaltimoreMaryland Department of Pathology University of MichiganDetroitMichiganUSA

The pathogenesis of ocular hemorrhage in abusive head trauma/shaken baby syndrome(AHT/SBS)is complex.Whereas severe hemorrhagic retinopathy has a robust association with AHT/SBS,mild disease is less specific.We report the ocular and cerebral findings in an 8‑month‑old girl with spastic torticollis who presented following confessed,violent sagittal plane acceleration‑deceleration with impact.Autopsy revealed subdural hemorrhage over the convexities,ischemic brain injury,and preexisting polymicrogyria.Ocular examination showed extensive but unilateral retinal hemorrhage,extending broadly to the ora serrata,with perimacular retinal folds and retinoschisis.The retina of the right globe was entirely normal.The findings in this case,suggest that movement of the globe within the orbit with acceleration‑deceleration,in this case greater on one side due to torticollis,may be the primary factor for severe hemorrhagic retinopathy associated with AHT/SBS.The findings argue against putative global mechanisms,such as intracranial hypertension.

关键词： Abusive head trauma forensic neuropathology forensic science hemorrhagic retinopathy retinal hemorrhage retinoschisis shaken baby syndrome

Controllable Transdermal Drug Delivery of Theobroma cacao Extract Based Polymeric Hydrogel against Dermal Microbial and Oxidative Damage

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Food and Nutrition Sciences 2019年第10期10卷 1212-1235页

作者： Shriya Agarwal Vandana Tyagi Mugdha Agarwal arushi Pant Harleen Kaur Rachana Manisha Singh Department of Biotechnology Jaypee Institute of Information Technology Noida India Amity Institute of Biotechnology Amity University Noida India.

Human dermal layers are directly bared to the external environmental adversities like pollution, radiation, dust along with various chemical and mechanical stress conditions which constantly lead to the oxidative stress, eventually forming free radicals. These conditions also support the dermal microbial infections by invading the cutaneous layers. Therefore, the most efficient approach accepted globally to combat these complications is to opt for transdermal application of exogenous antioxidants which helps in reducing the ill effects of oxidative stress and promotes the DNA repair. However, many scientific findings exhibited the potential role of Theobroma cacao for providing efficient skin protection. Theobroma cacao known for its vital procyanidin flavonoids, phenolic compounds, methylxanthines, catechin and epicatechin phytoconstituents with numerous health benefits, besides helping in smoothening and softening the damaged skin. These therapeutic benefits of cocoa phytocompounds are attributed to its anti-inflammatory and antioxidative characteristics. This study addresses the fabrication and optimizations of Theobroma cacao extract loaded carbopol hydrogel system for increased antioxidative and antimicrobial effects. It was found in the studies that the hydrogel-based T. cacao extract (TCHG) has significantly improved the therapeutic index of the extract, making it more suitable for transdermal application. The optimized hydrogel was further characterized by physicochemical parameters, SEM analysis and in-vitro release kinetics. The reported findings showed the sustained compound release with comparatively significant antimicrobial activity of TCHG against microbial (Pseudomonas fluorescens, Bacillus licheniformis, Micrococcus luteus, Aspergillus niger, Trichoderma harzianum, Rhizopus oryzae) infections. Also, the higher ROS quenching ability of TCHG as compared to T. cacao extract promises to be an effective transdermal formulation.

关键词： Theobromine Hydrogel Oxidative Stress Release Kinetics Transdermal