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Role of prostate cancer stem-like cells in the development of antiandrogen resistance

Cancer Drug Resistance 2022年第2期5卷 459-471页

作者： Prem Prakash Kushwaha Shiv verma Shashank Kumar Sanjay Gupta Department of Urology Case Western Reserve UniversityClevelandOH 44106USA. The Urology Institute University Hospitals Cleveland Medical CenterClevelandOH 44106USA. Molecular Signaling and Drug Discovery Laboratory Department of BiochemistryCentral University of PunjabBathinda 151401India. Department of Pathology Case Western Reserve UniversityClevelandOH 44106USA. Department of Pharmacology Case Western Reserve UniversityClevelandOH 44106USA. Department of Nutrition Case Western Reserve UniversityClevelandOH 44106USA. Divison of General Medical Sciences Case Comprehensive Cancer CenterClevelandOH 44106USA.

Androgen deprivation therapy(ADT)is the standard of care treatment for advance stage prostate cancer.Treatment with ADT develops resistance in multiple ways leading to the development of castration-resistant prostate cancer(CRPC).Present research establishes that prostate cancer stem-like cells(CSCs)play a central role in the development of treatment resistance followed by disease progression.Prostate CSCs are capable of self-renewal,differentiation,and regenerating tumor heterogeneity.The stemness properties in prostate CSCs arise due to various factors such as androgen receptor mutation and variants,epigenetic and genetic modifications leading to alteration in the tumor microenvironment,changes in ATP-binding cassette(ABC)transporters,and adaptations in molecular signaling pathways.ADT reprograms prostate tumor cellular machinery leading to the expression of various stem cell markers such as Aldehyde Dehydrogenase 1 Family Member A1(ALDH1A1),Prominin 1(PROM1/CD133),Indian blood group(CD44),SRY-Box Transcription Factor 2(Sox2),POU Class 5 Homeobox 1(POU5F1/Oct4),Nanog and ABC transporters.These markers indicate enhanced self-renewal and stemness stimulating CRPC evolution,metastatic colonization,and resistance to antiandrogens.In this review,we discuss the role of ADT in prostate CSCs differentiation and acquisition of CRPC,their isolation,identification and characterization,as well as the factors and pathways contributing to CSCs expansion and therapeutic opportunities.

关键词： Prostate cancer second-generation antiandrogens cancer stem cells castration resistance prostate cancer androgen deprivation therapy

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Role of Pathogen-Related Protein 10 (PR 10) under Abiotic and Biotic Stresses in Plants

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Phyton-International Journal of Experimental Botany 2020年第2期89卷 167-182页

作者： Rakesh Kumar Sinha shiv Shankar verma Anshu Rastogi Department of Plant Biophysics&Biochemistry Biology Center of the Czech Academy of SciencesInstitute of PlantMolecular BiologyCeskeBudejovice37005Czech Republic School of Medicine Case Western Reserve UniversityCleveland44106USA Department of Ecology and Environmental Protection Laboratory of BioclimatologyPoznan University of Life SciencesPoznan60-649Poland

Members of the Pathogenesis Related(PR)10 protein family have been identified in a variety of plant species and a wide range of functions ranging from defense to growth and development has been attributed to them.PR10 protein possesses ribonuclease(RNase)activity,interacts with phytohormones,involved in hormone-mediated signalling,afforded protection against various phytopathogenic fungi,bacteria,and viruses particularly in response to biotic and abiotic stresses.The resistance mechanism of PR10 protein may include activation of defense signalling pathways through possible interacting proteins involved in mediating responses to pathogens,degradation of RNA of the invading pathogens.Moreover,several morphological changes have been shown to accompany the enhanced abiotic stress tolerance.In this review,the possible mechanism of action of PR10 protein against biotic and abiotic stress has been discussed.Furthermore,our findings also confirmed that the in vivo Nitric oxide(NO)is essential for most of environmental abiotic stresses and disease resistance against pathogen infection.The proper level of NO may be necessary and beneficial,not only in plant response to the environmental abiotic stress,but also to biotic stress.The updated information on this interesting group of proteins will be useful in future research to develop multiple stress tolerance in plants.

关键词： Pathogenesis-related(PR) PR10 abiotic stress biotic stress ribonuclease stress tolerance nitric oxide

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Resistance to second generation antiandrogens in prostate cancer: pathways and mechanisms

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Cancer Drug Resistance 2020年第4期3卷 742-761页

作者： Shiv verma Kumari Sunita Prajapati Prem Prakash Kushwaha Mohd Shuaib Atul Kumar Singh Shashank Kumar Sanjay Gupta Department of Urology Case Western Reserve UniversityClevelandOH 44106USA The Urology Institute University Hospitals Cleveland Medical CenterClevelandOH 44106USA School of Basic and Applied Sciences Department of Biochemistry and Microbial SciencesCentral University of PunjabBathinda 151001India Department of Nutrition Case Western Reserve UniversityClevelandOH 44106USA Divison of General Medical Sciences Case Comprehensive Cancer CenterClevelandOH 44106USA Department of Urology Louis Stokes Cleveland Veterans Affairs Medical CenterClevelandOH 44106USA

Androgen deprivation therapy targeting the androgens/androgen receptor(AR)signaling continues to be the mainstay treatment of advanced-stage prostate cancer.The use of second-generation antiandrogens,such as abiraterone acetate and enzalutamide,has improved the survival of prostate cancer patients;however,a majority of these patients progress to castration-resistant prostate cancer(CRPC).The mechanisms of resistance to antiandrogen treatments are complex,including specific mutations,alternative splicing,and amplification of oncogenic proteins resulting in dysregulation of various signaling pathways.In this review,we focus on the major mechanisms of acquired resistance to second generation antiandrogens,including AR-dependent and AR-independent resistance mechanisms as well as other resistance mechanisms leading to CRPC emergence.Evolving knowledge of resistance mechanisms to AR targeted treatments will lead to additional research on designing more effective therapies for advanced-stage prostate cancer.

关键词： Prostate cancer second-generation antiandrogens androgen receptor castration resistance prostate cancer

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Inflammatory mediator release by Brugia malayi from macrophages of susceptible host Mastomys coucha and THP-1 and RAW 264.7 cell lines

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Asian Pacific Journal of Tropical Medicine 2011年第2期4卷 92-96页

作者： shiv Kumar verma Vikas Kushwaha Vijaya Dubey Kirti Saxena Aakanksha Sharma Puvvada Kalpana Murthy Division of Parasitology Central Drug Research InstituteCSIRLucknow 226001India

Objective:To investigate which life stage of the parasite has the ability to stimulate release of pro- or anti-inflammatory mediators from macrophages.Methods:The human macrophage/ monocyte cell line THP-1,the mouse macrophage cell line RAW 264.7 and naive peritoneal macrophages（PM） from the rodent host Mastomys coucha（M.coucha） were incubated at 37℃in 5%CO2 atmosphere with extracts of microfilariae（Mf）,third stage infective larvae（L3） and adult worms（Ad） of Brugia malayi.After 48 hr post exposure,IL-1β,IL-6,TNF-α,IL-10 and nitric oxide（NO） in cell-free supernatants were estimated.Results:Extracts of all the life stages of the parasite were capable of stimulating pro-（IL-1β,IL-6 and TNF-α） and anti-inflammatory （IL-10） cytokines in both the cell lines and peritoneal macrophages of M.coucha.Mf was the strongest stimulator of pro-inflammatory cytokines followed by L3 and Ad;however,Ad was a strong stimulator of IL-10 release.Mf was found to have potential to modulate LPS-induced NO release in RAW cells.Ad-induced NO release was concentration dependent with maximum at 20μg/mL in both RAW and PMs.Conclusions:The results show that parasites at all life stages were capable of stimulating pro-（IL-1β,IL-6 and TNF-α） and anti-inflammatory（IL-10） cytokines and NO release from macrophages of susceptible host M.coucha,human and mouse macrophage cell lines.Mf can suppress the LPS-induced NO release in RAW cells.The findings also show that the two cell lines may provide a convenient in vitro system for assaying parasite-induced inflammatory mediator release.

关键词： Cytokines Macrophage ThP-1 RAW 264.7 Brugia malayi Infective larva Microfilaria Adult worm Mastomys coucha

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Modeling the effect of time delay in implementation of mitigation policies on the control of atmospheric greenhouse gases

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生物数学学报:英文版 2023年第8期16卷 75-108页

作者： Alok Kumar verma Maitri verma Department of Mathematics School of Physical and Decision Science Babasaheb Bhimrao Ambedkar University Lucknow India

Mitigation of the enhanced greenhouse gas(GHG)concentrations in the Earth's atmosphere is imperative to meet the climate change mitigation objective.Governments of many countries are developing and implementing various mitigation strategies to reduce their GHG emissions.However,a time delay between the formulation and implementation of these mitigation policies can affect their effectiveness in controlling greenhouse gas levels in the atmosphere.This work presents a nonlinear mathematical model to investigate the effect of application of mitigation strategies and the delay involved in their implementation over the reduction of atmospheric greenhouse gases.In model formulation,it is assumed that the mitigation strategies work two-fold;first they reduce the GHG emission rate from the anthropogenic source and second they increase the removal rate of greenhouse gas from the atmosphere.A comprehensive stability analysis of the proposed model system is made to examine its long-term behavior.The model analysis shows that an increase in the implementation rate of mitigation strategies and their efficiencies to cut down the GHG emission rate from point sources and increase the GHG uptake rate lead to reduction in equilibrium GHG concentration.It is found that a long delay in the execution of mitigation policies can destabilize the system dynamics and leads to the generation of periodic oscillations.The expression for the threshold value of the delay parameter at which periodic oscillations arise via Hopf-bifurcation is determined.The stability and direction of bifurcating periodic solutions are discussed.A sensitivity analysis is performed to investigate the effect of changes in key parameters over system dynamics.

关键词： Mathematical model greenhouse gases global warming mitigation strategies time delay Hopf-bifurcation

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Dynamics of some new solutions to the coupled DSW equations traveling horizontally on the seabed

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Journal of Ocean Engineering and Science 2024年第2期9卷 154-163页

作者： Raj Kumar Ravi Shankar verma Department of Mathematics Faculty of Engineering&TechnologyVeer Bahadur Singh Purvanchal UniversityJaunpur 222003India

The system of(1+1)-coupled Drinfel’d-Sokolov-Wilson equations describes the surface gravity waves travelling horizontally on the seabed.The objective of the present research is to construct a new variety of analytical solutions for the system.The invariants are derived with the aid of Killing form by using the optimal algebra classification via Lie symmetry approach.The invariant solutions involve time,space variables,and arbitrary constants.Imposing adequate constraints on arbitrary constants,solutions are represented graphically to make them more applicable in designing sea models.The behavior of solutions shows asymptotic,bell-shaped,bright and dark soliton,bright soliton,parabolic,bright and kink,kink,and periodic nature.The constructed results are novel as the reported results[26,28,29,30,33,38,42,49]can be deduced from the results derived in this study.The remaining solutions derived in this study,are absolutely different from the earlier findings.In this study,the physical character of analytical solutions of the system could aid coastal engineers in creating models of beaches and ports.

关键词： Coupled Drinfel’d-Sokolov-Wilson model Invariants Killing form Optimal sub algebra Lie symmetry reductions

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Connections between biomechanics and higher infectivity: a tale of the D614G mutation in the SARS-CoV-2 spike protein

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Signal Transduction and Targeted Therapy 2021年第2期6卷 193-194页

作者： Anshumali Mittal Vikash verma Luxmi Nagar JaspurUttarakhandIndiaUniversity of MassachusettsAmherstMAUSA Biology Department University of MassachusettsAmherstMAUSA

Mutations are known to play a critical role in how a species evolves.In a recent article that appeared in the journal Cell,Yurkovetskiy et al.1 reported the structural and functional properties of the SARS-CoV-2 spike protein variant D614G that explains the basis of its increased infectivity.They observed that the mutant(D614G)was 4 to 9-fold more infectious than the wild type(D614),and the increased infectivity was not limited to human angiotensin-converting enzyme 2(ACE2).1 The cryo-EM structure suggested that D614G mutation weakens the stability of the homotrimer that shifts protein conformation towards an ACE2-binding fusion-competent state.1 The authors additionally showed that the D614G variant is neutralized by monoclonal antibodies targeting the spike protein receptor-binding domain(RBD).

关键词： ACE2 al. D61

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A Cooperative Approach of Frequency Regulation Through Virtual Inertia Control and Enhancement of Low Voltage Ride-through in DFIG-based Wind Farm

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Journal of Modern Power Systems and Clean Energy 2022年第6期10卷 1519-1530页

作者： Preeti verma Seethalekshmi K. Bharti Dwivedi Department of Electrical Engineering Institute of Engineering and TechnologyLucknow 226021Uttar PradeshIndiawhich is a constituent institute of Dr.A.P.J.Abdul Kalam Technical UniversityLucknowUttar Pradesh(U.P.)India IEEE

Doubly-fed induction generator(DFIG)-based wind farms(WFs)are interfaced with power electronic converters.Such interfaces are attributed to the low inertia generated in the WFs under high penetration and that becomes prevalent in a fault scenario.Therefore,transient stability enhancement along with frequency stability in DFIG-based WFs is a major concern in the present scenario.In this paper,a cooperative approach consisting of virtual inertia control(VIC)and a modified grid-side converter(GSC)approach for low voltage ride-through(LVRT)is proposed to achieve fault ride-through(FRT)capabilities as per the grid code requirements(GCRs)while providing frequency support to the grid through a synthetic inertia.The proposed approach provides LVRT and reactive power compensation in the system.The participation of the VIC in a rotor-side converter(RSC)provides frequency support to the DFIG-based WFs.The combined approach supports active power compensation and provides sufficient kinetic energy support to the system in a contingency scenario.Simulation studies are carried out in MATLAB/Simulink environment for symmetrical and unsymmetrical faults.The superiority of the proposed scheme is demonstrated through analysis of the performance of the scheme and that of a series resonance bridge-type fault current limiter(SR-BFCL).

关键词： Virtual inertia controller(VIC) doubly-fed induction generator(DFIG) fault ride-through(FRT)capability wind farm(WF) fault current limiter(FCL)

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Surface Modification Aspects for Improving Biomedical Properties in Implants:A Review

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Acta Metallurgica Sinica(English Letters) 2024年第2期37卷 213-241页

作者： J.Sharath Kumar Rakesh Kumar Rajeev verma Industrial and Production Department Dr B R Ambedkar National Institute of Technology JalandharJalandharPunjab144008India

The primary focus during surgery is to ensure successful implantation by achieving long-term and stable fixation of implants.Orthopaedic surgery is now more focused on the development of novel biomaterials intended to improve implant performance.To obtain a better understanding of metal implants,this article investigated the causes of material failures in certain cases and analysed a few case studies.The interaction between the implant and bone tissue was a crucial aspect of successful implantation,and this study explored the factors influencing this interaction as well as ways to improve it.Several modern approaches used for modifying implant surfaces were systematically illustrated and briefly analysed.Thermal spray coatings were often favoured because of their wide range of coating materials,but other substantial surface modifications(such as friction stir processing and laser surface texturing)were also used for a selection of applications.Notably,implant surfaces with desirable features,such as biocompatibility,antibacterial properties,corrosion resistance,and wear resistance,were essential for optimising implant functionality.This systematic review's main aim is to provide exhaustive reference information and a broad overview to advance the production and design of orthopaedic implants.

关键词： Biomaterials Surface treatments Thermal spray coatings Antibacterial Biocompatibility Corrosion resistance Wear resistance

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Battery energy storage-based system damping controller for alleviating sub-synchronous oscillations in a DFIG-based wind power plant

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Protection and Control of Modern Power Systems 2023年第2期8卷 260-277页

作者： Neevatika verma Narendra Kumar Rajeev Kumar Department of Electrical Engineering Delhi Technological UniversityNew DelhiIndia Electrical Engineering Department Jamia Millia IslamiaNew DelhiIndia Electrical and Electronics Engineering Department KIET Group of InstitutionsGhaziabadIndia

This paper presents the issue of the Sub-synchronous resonance(SSR)phenomenon in a series compensated DFIG-based wind power plant and its alleviation using a Battery Energy Storage-based Damping Controller(BESSDCL).A supplementary damping signal is developed considering the angular speed deviation and is incorporated into the BESS control system.Wide-area Measurement System data is used to determine the angular speed deviation.A lin-earized system model is developed to perform eigenvalue analysis,and to detect and examine unstable SSR modes.The variation of wind speed and three-phase fault are also taken into consideration to validate the robustness of the controller.To further verify the efficacy of the proposed damping controller,time-domain simulations are performed using MATLAB/Simulink.The application of the proposed BESSDCL stabilizes all the unstable system modes effectively at wind speeds of 7 m/s,9 m/s,and 11 m/s,and at 40%,50%,and 60%series compensation levels,as well three-phase fault conditions.

关键词： Battery energy storage system Damping controller Doubly-fed induction generator(DFIG) Series

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