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Multifaceted role of mTOR (mammalian target of rapamycin) signaling pathway in human health and disease

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Signal Transduction and Targeted Therapy 2023年第11期8卷 5159-5183页

作者： Vivek Panwar Aishwarya Singh Manini Bhatt Rajiv K.Tonk Shavkatjon Azizov Agha Saquib Raza Shinjinee Sengupta Deepak Kumar Manoj garg Department of Pharmaceutical Chemistry School of Pharmaceutical SciencesShoolini UniversitySolanHimachal Pradesh173229India Amity Institute of Molecular Medicine and Stem Cell Research(AIMMSCR) Amity University Uttar PradeshSector-125NoidaUttar Pradesh201313India Department of Biomedical Engineering Indian Institute of TechnologyRoparPunjab140001India Department of Pharmaceutical Chemistry School of Pharmaceutical SciencesDelhi Pharmaceutical Sciences and Research University(DPSRU)New Delhi110017India Laboratory of Biological Active Macromolecular Systems Institute of Bioorganic ChemistryAcademy of Sciences UzbekistanTashkent100125Uzbekistan Faculty of Life Sciences Pharmaceutical Technical University100084TashkentUzbekistan Rajive Gandhi Super Speciality Hospital TahirpurNew Delhi110093India

The mammalian target of rapamycin(mTOR)is a protein kinase that controls cellular metabolism,catabolism,immune responses,autophagy,survival,proliferation,and migration,to maintain cellular *** mTOR signaling cascade consists of two distinct multi-subunit complexes named mTOR complex 1/2(mTORC1/2).mTOR catalyzes the phosphorylation of several critical proteins like AKT,protein kinase C,insulin growth factor receptor(IGF-1R),4E binding protein 1(4E-BP1),ribosomal protein S6 kinase(S6K),transcription factor EB(TFEB),sterol-responsive element-binding proteins(SREBPs),Lipin-1,and Unc-51-like autophagy-activating *** signaling plays a central role in regulating translation,lipid synthesis,nucleotide synthesis,biogenesis of lysosomes,nutrient sensing,and growth factor *** emerging pieces of evidence have revealed that the constitutive activation of the mTOR pathway due to mutations/amplification/deletion in either mTOR and its complexes(mTORC1 and mTORC2)or upstream targets is responsible for aging,neurological diseases,and human ***,we provide the detailed structure of mTOR,its complexes,and the comprehensive role of upstream regulators,as well as downstream effectors of mTOR signaling cascades in the metabolism,biogenesis of biomolecules,immune responses,and ***,we summarize the potential of long noncoding RNAs(lncRNAs)as an important modulator of mTOR ***,we have highlighted the potential of mTOR signaling in aging,neurological disorders,human cancers,cancer stem cells,and drug ***,we discuss the developments for the therapeutic targeting of mTOR signaling with improved anticancer efficacy for the benefit of cancer patients in clinics.

关键词： metabolism homeostasis mTOR

An update on the role of medical treatment including antioxidant therapy in varicocele

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Asian Journal of Andrology 2016年第2期18卷 222-228,J0004页

作者： Harshit garg Rajeev Kumar Department of Urology All india Institute of Medical Sciences New Delhi India

Varicocele-associated male infertility has classically been managed using surgery or assisted reproductive techniques. With increasing evidence of oxidative stress as a pathophysiological factor in varicocele-associated infertility, medical therapy especially antioxidants might become a treatment option with lower risks. We reviewed the existing literature on the role of various medical agents in the management of male infertility attributed to varicoceles. Medical therapy is typically evaluated in three different situations such as （a） comparison of two drugs or one drug with placebo, （b） comparison of drugs versus surgery, and （c） comparison of drugs as adjuvant therapy with surgery versus drug therapy alone. Due to heterogeneity of data and lack of well-conducted studies, there is insufficient data to recommend routine use of medical therapy for men with varicocele-associated infertility and surgery remains the treatment of choice. Pregnancy and live birth rates are usually not reported in most studies and mere improvement in sperm parameters or antioxidant capacity is insufficient to support its routine use. Antioxidant therapy is a potential option due to its theoretical benefit, data from preclinical studies, and lack of major side effects. Adjuvant therapy with antioxidants after surgical repair of varicocele may improve the outcome and is a potential area for further research.

关键词： antioxidant therapy drug therapy male infertility varicocele

Multi-objective linear fractional inventory model with possibility and necessity constraints under generalised intuitionistic fuzzy set environment

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CAAI Transactions on Intelligence Technology 2019年第3期4卷 175-181页

作者： Totan Garai Harish garg Department of Mathematics Silda Chandra Sekhar CollegeJhargram-721515West BengalIndia School of Mathematics Thapar Institute of Engineering&TechnologyDeemed UniversityPatiala-147004PunjabIndia

This study presented a multi-objective linear fractional inventory (LFI) problem with generalised intuitionistic fuzzy numbers. In modelling, the authors have assumed the ambiances where generalised trapezoidal intuitionistic fuzzy numbers (GTIFNs) used to handle the uncertain information in the data. Then, the given multi-objective generalised intuitionistic fuzzy LFI model was transformed into its equivalent deterministic linear fractional programming problem by employing the possibility and necessity measures. Finally, the applicability of the model is demonstrated with a numerical example and the sensitivity analysis under several parameters is investigated to explore the study.

关键词： Multi-objective linear fractional inventory model possibility and necessity constraints generalised intuitionistic fuzzy set environment

Hesitant adopters:COVID-19 vaccine hesitancy among diverse vaccinated adults in the United States

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Infectious Medicine 2023年第2期2卷 89-95页

作者： Sharon Reece sheena CarlLee Aaron J.Scott Don E.Willis Brett Rowland Kristin Larsen Ijanae Holman-Allgood Pearl A.McElfish College of Medicine University of Arkansas for Medical Sciences NorthwestFayettevilleAR 72703USA Office of Community Health and Research University of Arkansas for Medical Sciences NorthwestSpringdaleAR 72703USA College of Medicine University of Arkansas for Medical Sciences NorthwestSpringdaleAR 72703USA

Background:Despite the United States(US)having an abundant supply of COVID-19 vaccines,vaccination rates lag behind other high-income countries,suggesting that vaccine hesitancy and attitudes play a greater role in public health measures than pure supply and *** the acknowledgment that vaccination attitudes and status may or may not be correlated,this study examined COVID-19 vaccine hesitancy among vaccinated US adults by asking:(1)What is the prevalence of COVID-19 vaccine hesitancy among the vaccinated?(2)Does COVID-19 vaccine hesitancy vary across sociodemographic characteristics?(3)Does COVID-19 vaccine hesitancy vary by healthcare access and influenza vaccination over the past 5 years?Methods:Data were collected through an online survey of 2022 US adults with a final analytic sample of 1383 vaccinated ***:Overall,48.8%of vaccinated adults reported some level of hesitancy,while a slight majority reported they were“not at all hesitant”.Younger respondents,women,and Black and American Indian or Alaska Native participants had greater adjusted odds of being more hesitant towards receiving the COVID-19 ***-dents who had a primary care physician had greater adjusted odds than those who did not have a primary care physician of being more hesitant towards receiving the COVID-19 ***:This is the first population-based national sample study examining COVID-19 vaccine hesitancy among vaccinated individuals from subgroups of distinctive backgrounds in order to inform targeted strategies for reducing vaccine *** can assist in efforts to increase vaccination rates and also decrease vaccine hesitancy at the national level.

关键词： COVID-19 vaccine Vaccine hesitancy Hesitant adopters US adults

Comments on ＂Some new distance measures for type-2 fuzzy sets and distance measure based ranking for group decision making problems＂

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Frontiers of Computer Science 2018年第2期12卷 396-400页

作者： Sukhveer SINGH Harish garg School of Mathematics Thapar University Patiala 147004 India

In this article, we have pointed out that some propositions corresponding to the distance measure between the type-2 fuzzy sets （T2FSs） as provided by Singh （Frontiers of Computer Science, 2014, 8（5）, 741-752）, are incorrect by a counterexample. Further, these propositions have been corrected in the present manuscript by giving a correct relation between the T2FSs and validating it with a numerical example.

关键词： type-2 fuzzy set distance measure incorrect assertion counterexample

Epithelial plasticity and cancer stem cells:Major mechanisms of cancer pathogenesis and therapy resistance

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World Journal of Stem Cells 2017年第8期9卷 118-126页

作者： Minal garg Department of Biochemistry University of LucknowLucknow 226007India

Epithelial-mesenchymal transition(EMT) has been linked with aggressive tumor biology and therapy resistance. It plays central role not only in the generation of cancer stem cells(CSCs) but also direct them across the multiple organ systems to promote tumor recurrence and metastasis. CSCs are reported to express stem cell genes as well as specific cell surfacemarkers and allow aberrant differentiation of *** facilitates cancer cells to leave primary tumor, acquire migratory characteristics, grow into new environment and develop radio-chemo-resistance. Based on the current information, present review discusses and summarizes the recent advancements on the molecular mechanisms that derive epithelial plasticity and its major role in generating a subset of tumor cells with stemness properties and pathophysiological spread of tumor. This paper further highlights the critical need to examine the regulation of EMT and CSC pathways in identifying the novel probable therapeutic *** improved therapeutic strategies based on the co-administration of inhibitors of EMT, CSCs as well as differentiated tumor cells may provide improved antineoplastic response with no tumor relapse.

关键词：上皮间充质的转变 Anticancer 治疗癌症干细胞分子的致病肿瘤恶化

Trichilia connaroides Wight an d Arnott:Ethnobotany,Phytochemistry and Pharmacology

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中国天然药物 2011年第4期9卷 241-248页

作者： Garima garg G.B.Pant University of Agriculture and Technology

Trichilia connaroides(Meliaceae) is an evergreen tree widely distributed in South and East *** has been traditionally used as an anti-feedant and in the treatment of cholera,arthritis,pharyngitis,tonsillitis and various other *** plant parts are rich in biologically active tetranortriterpenoids(limonoids) and possess good therapeutic *** present review illustrates the ethnobotanical uses and research advances till date on its phytochemical constituents and pharmacological activities so that its potential as a multipurpose medicinal agent is understood and appreciated.

关键词： Meliaceae Trichilia connaroides Tetranorterpenoids Limonoids

DNA Barcoding and Systematic Review of Minervaryan Frogs(Dicroglossidae:Minervarya) of Peninsular India:Resolution of a Taxonomic Conundrum with Description of a New Species

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Asian Herpetological Research 2021年第4期12卷 345-370页

作者： Sonali garg S.D.BIJU Systematics Lab Department of Environmental StudiesUniversity of Delhi

The genus Minervarya is among the most widely distributed,commonly occurring,and taxonomically confusing groups of dicroglossid frogs in *** studies have provided evidence that this genus contains complexes of morphologically conserved but genetically divergent taxa—some widely distributed across South and Southeast Asia,and many particularly restricted to the Western Ghats region of the Indian Peninsula—posing several challenges in resolving long-standing taxonomic ***,we present a systematic review of minervaryan species found in Peninsular India,based on extensive DNA barcoding with nearly 400 samples from the entire range of the genus,including 277 new samples and topotypic material for most available names from the study area,combined with detailed morphological *** a result,we recognise 18 species in Peninsular India,including a new species described herein as Minervarya pentali *** to the comprehensive nature of the study,including comparisons with all available types,certain long-standing taxonomic uncertainties on the status of ten previously known taxa are resolved Rana(Tomopterna)parambikulamana Rao,1937(=Minervarya parambikulamana),Rana(Hylorana)sauriceps Rao,1937(=Minervarya sauriceps),and Fejervarya kudremukhensis Kuramoto,Joshy,Kurabayashi,and Sumida,2008"2007"(=Minervarya kudremukhensis),are considered as junior subjective synonyms of Rana(Rana)limnocharis mysorensis Rao,1922(=Minervarya mysorensis);Nyctibatrachus sanctipdustris *** Rao,1920(=Minervarya modesta)is proposed to be a synonym of Rana limnocharis syhadrensis Annandale,1919(=Minervarya syhadrensis);while Rana murthii Pillai,1979(=Minervarya murthii)and Fejervarya mudduraja Kuramoto,Joshy,Kurabayashi,and Sumida,2008"2007"(=Minervarya mudduraja)are considered as junior subjective synonyms of Rana nilagirica Jerdon,1853(=Minervarya nilagirica).At the same time,Rana brevipalmata Peters,1871(=Minervarya brevipalmata),previously known only from its ori

关键词： amphibia distribution Fejervarya integrative taxonomy Minervarya pentali sp.nov. morphology species groups Western Ghats Biodiversity Hotspot

Publish/subscribe based information dissemination over VANET utilizing DHT

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Frontiers of Computer Science 2012年第6期6卷 713-724页

作者： Tulika PANDEY Deepak garg Manoj Madhav GORE Department of Computer Science and IT Sam Higginbotom Institute of AgricultureTechnology and SciencesAllahabad 211007India Department of Computer Science and Engineering Thapar UniversityPatiala 147004India Department of Computer Science and Engineering Motilal Nehru National Institute of TechnologyAllahabad 211004India

A vehicular ad-hoc network （VANET） can be visualized as a network of moving vehicles communicating in an asynchronous and autonomous fashion. Efficient and scalable information dissemination in VANET applications is a major challenge due to the movement of vehicles which causes unpredictable changes in network topology. The publish/subscribe communication paradigm provides decoupling in time, space, and synchronization between communicating entities, and presents itself as an elegant solution for information dissemination for VANET like environments. In this paper, we propose our approach for information dissemination which utilizes publish/subscribe and distributed hash table （DHT） based overlay networks. In our approach, we assume a hybrid VANET consisting of stationary info-stations and moving vehicles. These info-stations are installed at every major intersection of the city and vehicles can take the role of publisher, subscriber, or broker depending upon the context. The info-stations form a DHT based broker overlay among themselves and act as rendezvous points for related publications and subscriptions. Further, info-stations also assist in locating vehicles that have subscribed to information items. We consider different possible deployments of this hybrid VANET with respect to the number of info-stations and their physical connectivity with each other. We perform simulations to assess the performance of our approach in these different deployment scenarios and discuss their applicability in urban and semi-urban areas.

关键词： vehicular ad-hoc network (VANET) peer-to- peer overlay network publish/subscribe communication paradigm distributed hash table (DHT)