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SARS-CoV2 Nsp3 protein triggers cell death and exacerbates amyloid β42-mediated neurodegeneration

Neural Regeneration Research 2024年第6期19卷 1385-1392页

作者： Aditi Singh Anuradha Venkatakrishnan Chimata prajakta deshpande Soumya Bajpai Anjali Sangeeth Mrigendra Rajput Amit Singh Department of Biology University of Dayton Premedical Program University of Dayton Center for Tissue Regeneration and Engineering at Dayton (TREND) University of Dayton The Integrative Science and Engineering Center University of Dayton Center for Genomic Advocacy (TCGA) Indiana State University

Infection caused by the severe acute respiratory syndrome coronavirus 2(SARS-CoV2) virus, responsible for the coronavirus disease 2019(COVID-19) pandemic, induces symptoms including increased inflammatory response, severe acute respiratory syndrome(SARS), cognitive dysfunction like brain fog, and cardiovascular defects. Long-term effects of SARS-CoV2 COVID-19 syndrome referred to as post-COVID-19 syndrome on age-related progressive neurodegenerative disorders such as Alzheimer’s disease remain understudied. Using the targeted misexpression of individual SARS-CoV2 proteins in the retinal neurons of the Drosophila melanogaster eye, we found that misexpression of nonstructural protein 3(Nsp3), a papain-like protease, ablates the eye and generates dark necrotic spots. Targeted misexpression of Nsp3 in the eye triggers reactive oxygen species production and leads to apoptosis as shown by cell death reporters, terminal deoxynucleotidyl transferase(TdT) dUTP Nick-end labeling(TUNEL) assay, and dihydroethidium staining. Furthermore, Nsp3 misexpression activates both apoptosis and autophagy mechanism(s) to regulate tissue homeostasis. Transient expression of SARS-CoV2 Nsp3 in murine neuroblastoma, Neuro-2a cells, significantly reduced the metabolic activity of these cells and triggers cell death. Misexpression of SARS-CoV2 Nsp3 in an Alzheimer’s disease transgenic fly eye model(glass multiple repeats [GMR]>amyloid β42) further enhances the neurodegenerative rough eye phenotype due to increased cell death. These findings suggest that SARS-CoV2 utilizes Nsp3 protein to potentiate cell death response in a neurodegenerative disease background that has high pre-existing levels of neuroinflammation and cell death.

关键词： Alzheimer's disease apoptosis autophagy COVID-19 Drosophila necrosis Neuro-2a cells neurodegeneration post COVID-19 syndrome SARS-CoV2

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Exploring the efficacy of natural products in alleviating Alzheimer’s disease

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Neural Regeneration Research 2019年第8期14卷 1321-1329页

作者： prajakta deshpande Neha Gogia Amit Singh Department of Biology University of Dayton Dayton OH USA Premedical Program University of Dayton Dayton OH USA Center for Tissue Regeneration and Engineering at Dayton (TREND) University of Dayton Dayton OH USA The Integrative Science and Engineering Center University of Dayton Dayton OH USA Center for Genomic Advocacy (TCGA) Indiana State University Terre Haute IN USA

Alzheimer’s disease(hereafter AD) is a progressive neurodegenerative disorder that affects the central nervous system. There are multiple factors that cause AD, viz., accumulation of extracellular Amyloid-beta 42 plaques, intracellular hyper-phosphorylated Tau tangles, generation of reactive oxygen species due to mitochondrial dysfunction and genetic mutations. The plaques and tau tangles trigger aberrant signaling, which eventually cause cell death of the neurons. As a result, there is shrinkage of brain, cognitive defects, behavioral and psychological problems. To date, there is no direct cure for AD. Thus, scientists have been testing various strategies like screening for the small inhibitor molecule library or natural products that may block or prevent onset of AD. Historically, natural products have been used in many cultures for the treatment of various diseases. The research on natural products have gained importance as the active compounds extracted from them have medicinal values with reduced side effects, and they are bioavailable. The natural products may target the proteins or members of signaling pathways that get altered in specific diseases. Many natural products are being tested in various animal model systems for their role as a potential therapeutic target for AD, and to address questions about how these natural products can rescue AD or other neurodegenerative disorders. Some of these products are in clinical trials and results are promising because of their neuroprotective, anti-inflammatory, antioxidant, anti-amyloidogenic, anticholinesterase activities and easy availability. This review summarizes the use of animal model systems to identify natural products, which may serve as potential therapeutic targets for AD.

关键词： Alzheimer’s disease amyloid-beta 42 natural products Lunasin neuroprotective anti-inflammation antioxidant Drosophila cell death neurodegeneration

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Signaling interactions among neurons impact cell fitness and death in Alzheimer's disease

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Neural Regeneration Research 2023年第4期18卷 784-789页

作者： Catherine Yeates prajakta deshpande Madhuri Kango-Singh Amit Singh Department of Biology University of DaytonDaytonOHUSA Premedical Program University of DaytonDaytonOHUSA Center for Tissue Regeneration and Engineering at Dayton(TREND) University of DaytonDaytonOHUSA The Integrative Science and Engineering Center University of DaytonDaytonOHUSA Center for Genomic Advocacy(TCGA) Indiana State UniversityTerre HauteINUSA

The pathology of Alzheimer’s disease involves a long preclinical period,where the characteristic clinical symptoms of the changes in the brain are *** the preclinical period,homeostatic mechanisms may help prevent widespread cell *** has pointed towards selective cell death of diseased neurons playing a potentially protective *** the disease progresses,dysregulation of signaling pathways that govern cell death contributes to *** activation of the c-Jun N-terminal kinase pathway has been established in human and animal models of Alzheimer’s disease caused by amyloid-beta 42-or tau-mediated *** mosaic studies in Drosophila that examine amyloid-beta 42 in a subset of neurons suggest complex interplay between amyloid-beta 42-expressing and wild-type *** review examines the role of c-Jun N-terminal kinase signaling in the context of cell competition and short-range signaling interactions between amyloid-beta 42-expressing and wild-type *** competition is a conserved phenomenon regulating tissue integrity by assessing the fitness of cells relative to their neighbors and eliminating suboptimal *** clones of amyloid-beta 42 that juxtapose genetically distinct neuronal cell populations show promise for studying *** genetic mosaics with labeled clones of amyloid-beta 42-or tau-expressing and wild-type neurons will allow us to understand how short-range signaling alterations trigger cell death in neurons and thereby contribute to the progression of Alzheimer’s *** approaches have the potential to uncover biomarkers for early Alzheimer’s disease detection and new therapeutic targets for intervention.

关键词： Alzheimer’s disease amyloid-beta 42 mediated neurodegeneration cell competition Drosophila c-Jun N-terminal kinase signaling suboptimal cell super competition super competitor cell two clone-approach wild type cell

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Hippo signaling:bridging the gap between cancer and neurodegenerative disorders

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Neural Regeneration Research 2021年第4期16卷 643-652页

作者： Neha Gogia Anuradha Venkatakrishnan Chimata prajakta deshpande Aditi Singh Amit Singh Department of Biology University of DaytonDaytonOHUSA Medical Candidate University of Toledo College of Medicine and Life SciencesToledoOHUSA Premedical Program University of DaytonDaytonOHUSA Center for Tissue Regeneration and Engineering at Dayton(TREND) University of DaytonDaytonOHUSA The Integrative Science and Engineering Center University of DaytonDaytonOHUSA Center for Genomic Advocacy(TCGA) Indiana State UniversityTerre HauteINUSA

During development,regulation of organ size requires a balance between cell proliferation,growth and cell *** of these fundamental processes can cause a variety of *** cell proliferation results in cancer whereas excessive cell death results in neurodegenerative *** signaling pathways known-to-date have a role in growth *** them,evolutionarily conserved Hippo signaling pathway is unique as it controls both cell proliferation and cell death by a variety of mechanisms during organ sculpture and ***,a complex process of progressive death of neuronal population,results in fatal disorders with no available cure to *** normal development,cell death is required for sculpting of an ***,aberrant cell death in neuronal cell population can result in neurodegenerative *** pathway has gathered major attention for its role in growth regulation and cancer,however,other functions like its role in neurodegeneration are also emerging *** review highlights the role of Hippo signaling in cell death and neurodegenerative diseases and provide the information on the chemical inhibitors employed to block Hippo *** Hippo mediated cell death mechanisms will aid in development of reliable and effective therapeutic strategies in future.

关键词： animal models cell death mechanisms cell-signaling chemical inhibitors Drosophila eye Hippo pathway neurodegeneration neurological diseases therapeutic targets

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Starch based nanofibrous scaffolds for wound healing applications

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Bioactive Materials 2018年第3期3卷 255-266页

作者： Vijaya Sadashiv Waghmare Pallavi Ravindra Wadke Sathish Dyawanapelly Aparna deshpande Ratnesh Jain prajakta Dandekar Department of Pharmaceutical Sciences and Technology Institute of Chemical TechnologyMatungaMumbai 400019India Department of Chemical Engineering Institute of Chemical TechnologyMatungaMumbai 400019India Department of Physics Indian Institute of Science Education and Research(IISER)PashanPune 411008India

Starch is an attractive polymer for wound healing applications because of its wide availability,low cost,biocompatibility,biodegradability and wound-healing ***,we have fabricated starch-based nanofibrous scaffolds by electrospinning for wound healing *** diameter of the optimized nanofibers was determined by field emission scanning electron microscopy(FE-SEM)and was found to be in the range of 110e300 *** mechanical strength(0.5e0.8 MPa)of the nanofibrous scaffolds was attuned using polyvinyl alcohol(plasticizer)and glutaraldehyde(crosslinking agent),to impart them with sufficient durability for skin tissue *** of negative interactions between the polymers was confirmed by Attenuated Total Reflectance-Fourier Transform Infrared Spectroscopy(ATR-FTIR),differential scanning microscopy(DSC)and thermal gravimetric analysis(TGA).Cellular assays with L929 mouse fibroblast cells indicated the ability of the scaffolds to promote cellular proliferation,without exhibiting any toxic effect to the ***,the nanofibrous scaffolds demonstrated potential for wound healing applications.

关键词： Starch Nanofibers Electrospinning Scaffold Wound healing

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Molecular dynamics study on growth of carbon dioxide and methane hydrate from a seed crystal

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Chinese Journal of Chemical Engineering 2019年第9期27卷 2074-2080页

作者： prajakta Nakate Bappa Ghosh Subhadip Das Sudip Roy Rajnish Kumar Chemical Engineering and Process Development National Chemical LaboratoryPune 411008India Physical and Materials Chemistry Division National Chemical LaboratoryPune 411008India Department of Chemistry Chaudhary Ranbir Singh UniversityfindHaryana-126102 Department of Chemical Engineering Indian Institute of TechnologyMadrasChennai 600036Tamil NaduIndia

In the current work,molecular dynamics simulation is employed to understand the intrinsic growth of carbon dioxide and methane hydrate starting from a seed crystal of methane and carbon dioxide *** comparison was carried out because it has relevance to the recovery of methane gas from natural gas hydrate reservoirs by simultaneously sequestering a greenhouse gas like *** seed crystal of carbon dioxide and methane hydrate was allowed to grow from a super-saturated mixture of carbon dioxide or methane molecules in water *** different concentrations(1:6 and 1:8.5)of CO2/CH4 molecules per water molecule were chosen based on gas–water composition in hydrate *** molecular level growth as a function of time was investigated by all atomistic molecular dynamics simulation under suitable temperature and pressure range which was well above the hydrate stability zone to ensure significantly faster growth *** concentration of CO2 molecules in water played a significant role in growth kinetics,and it was observed that maximizing the CO2 concentration in the aqueous phase may not result in faster growth of CO2 *** the contrary,methane hydrate growth was independent of methane molecule concentration in the aqueous *** have validated our results by performing experimental work on carbon dioxide hydrate where it was seen that under conditions appropriate for liquid CO2,the growth for carbon dioxide hydrate was very slow in the beginning.

关键词： CH4 recovery Natural gas hydrate CO2 sequestration Kinetics F4 order parameter Cage dynamics Thermodynamics

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Characteristics and distinct prognostic determinants of individuals with hepatosplenic T-cell lymphoma over the past two decades

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World Journal of Clinical Oncology 2024年第6期15卷 745-754页

作者： Ayrton Bangolo Pierre Fwelo Shraboni Dey Tanni Sethi Sowmya Sagireddy Jawaria Chatta Ashish Goel Sneha Nagpaul Eric Pin-Shiuan Chen Chiranjeeve Saravanan Sheeja Gangan Joel Thomas Sarah Potiguara Vignesh K Nagesh Daniel Elias Charlene Mansour prajakta H Ratnaparkhi Priyanshu Jain Midhun Mathew Taylor Porter Shadiya Sultan Shailaja Abbisetty Linh Tran Megha Chawla Abraham Lo Simcha Weissman Christina Cho Department of Internal Medicine Palisades Medical CenterNorth BergenNJ 07047United States Department of Epidemiology Human Geneticsand Environmental SciencesUTHealth School of Public HealthHoustonTX 77030United States Department of Medicine Palisades Medical CenterNorth BergenNJ 07047United States Stem Cell Transplantation and Cellular Therapy John Theurer Cancer CenterHackensackNJ 07601United States

BACKGROUND Hepatosplenic T-cell lymphoma(HSTCL)is a rare and aggressive peripheral T-cell lymphoma with historically dismal outcomes,representing less than one percent of non-Hodgkin *** its rarity,the true incidence of HSTCL is unknown and most data have been extrapolated through case *** the best of our knowledge,the largest and most up to date study addressing the epidemiology and outcomes of patients with HSTCL in the United States covered a period from 1996 to 2014,with a sample size of 122 *** To paint the most updated epidemiological picture of *** A total of 186 patients diagnosed with HSTCL,between 2000 and 2017,were ultimately enrolled in our study by retrieving data from the Surveillance,Epidemiology,and End Results *** analyzed demographics,clinical characteristics,and overall mortality(OM)as well as cancer-specific mortality(CSM)of *** with a P value<0.01 in the univariate Cox regression were incorporated into the multivariate Cox model to determine the independent prognostic factors,with a hazard ratio of greater than 1 representing adverse prog-nostic *** Overall,the outlook for this rare malignancy is very *** this retrospective cohort study of the United States population,non-Hispanic blacks and the elderly had a higher *** data highlights the need for larger prospective studies to investigate factors associated with worse prognosis in one ethnic group,such as treatment delays,which have been shown to increase mortality in this racial/ethnic group for other cancers.

关键词： Extra nodal lymphoma Mortality Survival Racial disparity Age

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Performance of waist circumference relative to BMI in predicting risk of obesity and hypertension among affluent Indian adults

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Health 2013年第8期5卷 16-22页

作者： Shobha Rao prajakta Parab-Waingankar Biometry and Nutrition Unit Agharkar Research Institute Pune India

In view of the fact that Asians have higher abdominal fat at lower levels of body mass index (BMI), measures of abdominal adiposity such as waist circumference (WC) and waist to hip ratio (WHR) were investigated as predictors of hypertension. Data on BMI, WC, WHR and blood pressure (BP) were recorded through a cross-sectional study on 419 urban adults (210 men and 209 women;aged 30-60 years) in Pune, India. Abdominal obesity was higher among women than men (35.9% vs. 32.4%). However, age adjusted mean systolic BP (124.3 ± 15.1 mmHg vs. 114.7 ± 17.2 mmHg), diastolic BP (82.9 ± 10.5 mmHg vs. 76.4 ± 10.7 mmHg) and prevalence of hypertension (34.3% vs. 21.5%) was significantly higher (p < 0.01) among men than among women. Although both WC and WHR increased with increase in BMI, correlation coefficient of BMI with WC was significantly (p < 0.01) higher than that with WHR in both sexes, suggesting that WC could be better for assessing adiposity. In men, odds ratio [OR (95% CI) = 2.19 (1.08-4.45)] for hypertension was significant (p < 0.05) only for those in highest tertile of WC while it was significant (p < 0.01) even in the middle tertile in case of women [8.24 (2.67-25.43) for higher and 5.71 (1.82-17.89) for middle tertile]. Optimal cutoff for identifying obesity and hypertension showed significant (p < 0.01) area under curve (AUC) and sensitivity for WC than WHR in both sexes. The risk cutoffs were lower compared to those proposed by the World Health Organization especially for men, but were comparable with reported Asian studies. Thus, it was evident that WC performed better than BMI and WHR for assessing the risk of hypertension and may be used as a simple, convenient and inexpensive screening tool in epidemiological studies.

关键词： Abdominal Adiposity Asians Blood Pressure Body Mass Index Waist Circumference Waist to Hip Ratio

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Analysis of RFID Based Positioning Technique Using Received Signal Strength and Directional Antenna

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Positioning 2016年第2期7卷 80-89页

作者： prajakta Shirke Amol Potgantwar V. M. Wadhai Department of Computer Engineering Sandip Foundation’s Sandip Institute of Technology and Research Centre Nashik India Sinhgad College of Academy Pune India

Automatic robot navigation is being utilized in many industries for the purpose of high speed work delivery. Color follower, fix path follower robots are current solution to this activities but dynamic path configuration is not possible in these robots. Hence new system proposes effective and fully dynamic path follower robots using RFID and directional antenna. Radio Frequency Identification (RFID) system permits automatic identification of objects with RFID tags using radio waves which have been widely used in mobile robot navigation, localization and mapping both in indoor and outdoor environment. This article presents a navigation strategy for autonomous mobile robot using passive RFID system. Proposed robot system is provided with RFID tag functionality which will load tag number and direction instruction. At some turning point, user will put RF tag, this tag will be read by RF reader which is placed on robot. As per direction instruction robot will change the direction and reach to the destination. Also as per the movement, robot will send its GPS location to PC (Personal Computer) which will be displayed on PC. Hence main goal is to provide more reliable and low energy consumption based indoor positioning system which will be achieved using directional antenna.

关键词： Global Positioning System (GPS) Indoor Positioning System (IPS) Radio Frequency Identification (RFID) Received Signal Strength (RSS)

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Molecular dynamics study on growth of carbon dioxide and methane hydrate from a seed crystal

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中国化学工程学报（英文版） 2019年第9期

作者： prajakta Nakate Bappa Ghosh Subhadip Das Sudip Roy Rajnish Kumar

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