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Potential role of nimbolide in chemoprevention and therapy of prostate cancer

中国药理学与毒理学杂志 2015年第S1期29卷 78-79页

作者： Jing-wen ZHANG MuthuK.SHANMUGAM Amudha DEIVASIGAMANI alan prem kumar KamMan HUI Gautam SETHI Department of Pharmacology Yong Loo Lin School of Medicine National University of Singapore Singapore 117597 Division of Cellular and Molecular Research Humphrey Oei Institute of Cancer Research National Singapore 1169610 Cancer Centre Cancer Science Institute of Singapore Centre for Translational Medicine Singapore 117599

OBJECTIVE Prostate cancer is one of the most commonly diagnosed cancers *** therapies for metastatic prostate cancer are only marginally effective,and hence novel treatment modalities are urgently *** evidence suggests that chronic inflammation plays a pivotal role in the development and progression of prostate *** agents that can suppress these inflammatory mediators could form the basis of novel therapy for prostate cancer *** our study,we focused on analyzing the potential anticancer effects of nimbolide,a terpenoid lactone derived from Azadirachta indica(Neem tree)against prostate *** Molecular biology techniques such as western blot analysis,DNA binding,luciferase assays,and immunohistochemistry were used for both in vitro and in vivo *** Data from the in vitrostudies indicated that nimbolide could inhibit cell proliferation,induce apoptosis and suppress cellular invasion and ***,nimbolide also abrogated the activation of pro-inflammatory STAT 3 transcription factor,and this effect was found to be mediated via an increased production of reactive oxygen species(ROS),whereas depletion of ROS attenuated pSTAT 3 inhibitory effects of the *** in vivo efficacy of nimbolide was also noted in transgenic adenocarcinoma of mouse prostate(TRAMP)model,in which this triterpenoid significantly suppressed the tumor progression and growth without exhibiting any substantial adverse *** Overall our findings indicate that nimbolide exhibits significant anticancer effects in prostate cancer,and these effects may be mediated at least in part through the modulation of STAT 3 signaling pathway.

关键词： prostate cancer nimbolide STAT3 ROS

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Targeting the PI3K/Akt signaling pathway in gastric carcinoma: A reality for personalized medicine?

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World Journal of Gastroenterology 2015年第43期21卷 12261-12273页

作者： Shikha Satendra Singh Wei Ney Yap Frank Arfuso Shreya Kar Chao Wang Wanpei Cai Arunasalam M Dharmarajan Gautam Sethi alan prem kumar Cancer Science Institute of Singapore National University of Singapore Department of Pharmacology Yong Loo Lin School of MedicineNational University of Singapore Davos Life Science Pte Ltd School of Biomedical Sciences Curtin Health Innovation Research InstituteCurtin University National University Cancer Institute Department of Biological Sciences University of North Texas

Frequent activation of phosphatidylinositol-3 kinases(PI3K)/Akt/m TOR signaling pathway in gastric cancer(GC) is gaining immense popularity with identification of mutations and/or amplifications of PIK3 CA gene or loss of function of PTEN,a tumor suppressor protein,to name a few; both playing a crucial role in regulating this pathway. These aberrations result in dysregulation of this pathway eventually leading to gastric oncogenesis,hence,there is a need for targeted therapy for more effective anticancer treatment. Several inhibitors are currently in either preclinical or clinical stages for treatment of solid tumors like GC. With so many inhibitors under development,further studies on predictive biomarkers are needed to measure the specificity of any therapeutic intervention. Herein,we review the common dysregulation of PI3K/Akt/m TOR pathway in GC and the various types of single or dual pathway inhibitors under development that might have a superior role in GC treatment. We also summarize the recent developments in identification of predictive biomarkers and propose use of predictive biomarkers to facilitate more personalized cancer therapy with effective PI3K/Akt/m TOR pathway inhibition.

关键词： Epidemiology Gastric cancer PI3K/Akt/ m TOR pathwa

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Garcinol suppresses the growth of human hepatocellular carcinoma by inducing abrogation of STAT3 phosphorylation,acetylation and dimerization

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中国药理学与毒理学杂志 2015年第S1期29卷 82-83页

作者： Muthu K SHANMUGAM Snehajyoti CHATTERJEE Peramaiyan RAJENDRAN Feng LI Parijat SENAPATI Kwong Fai WONG alan prem kumar John MLUK Kam Man HUI Gautam SETHI Tapas K KUNDU Department of Pharmacology Yong Loo Lin School of Medicine National University of Singapore Singapore 117957 Jawaharlal Nehru Centre for Advanced Scientific Research Molecular Biology and Genetics Unit Transcription and Disease Laboratory Jakkur P.O. Bangalore 560064 India Cancer Science Institute of Singapore National University of Singapore Singapore 117456 School of Biomedical Sciences Faculty of Health Sciences Curtin University Western Australia Division of Cellular and Molecular Research Humphrey Oei Institute of Cancer Research National Cancer Centre Singapore 169610 Institute of Molecular and Cell Biology Singapore 138673

OBJECTIVE Hepatocellular carcinoma(HCC)is the fifth most common malignancy worldwide and the third cause of global cancer *** of signal transducer and activator of transcription 3(STAT3)is commonly observed in tumor cells and is a critical mediator of on cogenic signaling in HCC and controls the expression of several genes involved in proliferation,survival,metastasis and *** drug-targeted therapies,besides being expensive,are associated with serious side effects and ***,novel agents that can suppress STAT3 activation have potential for both prevention and treatment of *** the present report,we investigated whether the potent HAT/KAT inhibitor,garcinol,(apolyisoprenylatedbenzophenone),could suppress STAT3 activation in HCC cells and in nude mice *** The effect of garcinol on HCC cell lines wasdetermined by MTT assay,immunoblotting,DNA binding assays,immuno-fluorescenceand immune-histochemical *** effect of garcinolon the inhibition of tumor growth in vivo was also investigated using HCCxenograft tumor modelin athymic nu/nu *** We found that garcinol could inhibit constitutive STAT3 activation in a dose-and time-dependent manner both by inhibiting STAT3 phosphorylation and acetylation in HCC *** investigated for molecular mechanism(s),we found that garcinol interferes with the dimer formation of STAT3 thereby inhibits its nuclear *** modeling showed that garcinol could bind to the SH2 domain of STAT3 and suppresses its dimerization in *** understand the cellular mechanism(s)of inhibition of STAT3 function by garcinol,we observed that upon inhibition of STAT3 dimerization bygarcinol,STAT3 DNA binding ability gets *** inhibition of STAT3 activation by garcinol led to the suppression of various gene products involved in proliferation,survival,and ***,when administered i.p.,garcinol inhibited the growth of human HCC xenograft tumors in

关键词： STAT3 HCC garcinol acetylation dimerization nude m

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Garcinol sensitizes human head and neck carcinoma to cisplatin in a xenograft mouse model despite downregulation of proliferative biomarkers

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中国药理学与毒理学杂志 2015年第S1期29卷 80-80页

作者： Feng Li Muthu K. Shanmugam Kodappully Sivaraman Siveen Fan Wang Tina H. Ong Ser Yue Loo Mahadeva M.M. Swamy Somnath Mandal alan prem kumar Boon Cher Goh Tapas Kundu Kwang Seok Ahn Ling Zhi Wang Kam Man Hui Gautam Sethi Department of Pharmacology Yong Loo Lin School of Medicine National University of Singapore Singapore 117957 Cancer Science Institute of Singapore Centre for Translational Medicine Singapore 117957 Division of Cellular and Molecular Research Humphrey Oei Institute of Cancer Research National Cancer Centre Singapore 169610 Genome Institute of Singapore Agency for Science Technology and Research (A*STAR) Singapore Jawaharlal Nehru Centre for Advanced Scientific Research Molecular Biology and Genetics Unit Transcription and Disease Laboratory Bangalore 560064 India School of Biomedical Sciences Faculty of Health Sciences Curtin University Western Australia 6009 Australia Department of Biological Sciences University of North Texas Denton Texas 76203 Department of Haematology-Oncology National University Health System Singapore 117957 College of Korean Medicine Kyung Hee University Seoul 130-701 Republic of Korea

OBJECTIVE Platinum compounds such as cisplatin and carboplatin are frequently used as the first-line chemotherapy for the treatment of the head and neck squamous cell carcinoma(HNSCC).In the present study,we investigated whether garcinol,apolyisoprenylated benzophenone can chemosensitize HNSCC to *** The effect of garcinol and cisplatin on HNSCC was assessed by MTT,Western blotting,real time PCR,FACS,immunohistochemistry,DNA binding assay and xenograft mouse *** We found that garcinol inhibited the viability of a panel of diverse HNSCC cell lines,enhanced the apoptotic effect of cisplatin,suppressed constitutive as well as cisplatin-induced NF-κB activation,and downregulated the expression of various oncogenic gene products(cyclin D1,Bcl-2,survivin and VEGF).In vivo study showed that administration of garcinol alone(0.5 mg·kg-1,ip five times/week)significantly suppressed the growth of the tumor,and this effect was further increased by *** the markers of proliferation index(Ki-67)and microvessel density(CD31)were downregulated in tumor tissues by the combination of cisplatin and *** pharmacokinetic results of garcinol indicated that good systemic exposure was achievable after ip administration of garcinol at 0.5and 2mg·kg-1 with mean peak concentration(cmax)of 1825.4 and 6635.7nmol·L-1 in the mouse serum,*** Overall,our results suggest that garcinol can indeed potentiate the effects of cisplatin by negative regulation of various inflammatory and proliferative biomarkers.

关键词： HNSCC chemoresistance NF-κB proliferation garcinol

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Recent advances in catalytic combustion of AP-based composite solid propellants

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Defence Technology（防务技术） 2021年第3期17卷 1013-1031页

作者： Narendra Yadav prem kumar Srivastava Mohan Varma Department of Space Engineering&Rocketry India Department of Chemistry Birla Institute of TechnologyMesraRanchiIndia

Composite solid propellants(CSPs) have widely been used as main energy source for propelling the rockets in both space and military applications. Internal ballistic parameters of rockets like characteristic exhaust velocity, specific impulse, thrust, burning rate etc., are measured to assess and control the performance of rocket motors. The burn rate of solid propellants has been considered as most vital parameter for design of solid rocket motors to meet specific mission requirements. The burning rate of solid propellants can be tailored by using different constituents, extent of oxidizer loading and its particle size and more commonly by incorporating suitable combustion catalysts. Various metal oxides(MOs),complexes, metal powders and metal alloys have shown positive catalytic behaviour during the combustion of CSPs. These are usually solid-state catalysts that play multiple roles in combustion of CSPs such as reduction in activation energy, enhancement of rate of reaction, modification of sequences in reaction-phase, influence on condensed-phase combustion and participation in combustion process in gas-phase reactions. The application of nanoscale catalysts in CSPs has increased considerably in recent past due to their superior catalytic properties as compared to their bulk-sized counterparts. A large surface-to-volume ratio and quantum size effect of nanocatalysts are considered to be plausible reasons for improving the combustion characteristics of propellants. Several efforts have been made to produce nanoscale combustion catalysts for advanced propellant formulations to improve their energetics. The work done so far is largely scattered. In this review, an effort has been made to introduce various combustion catalysts having at least a metallic entity. Recent developments of nanoscale combustion catalysts with their specific merits are discussed. The combustion chemistry of a typical CSP is briefly discussed for providing a better understanding on role of co

关键词： Composite solid propellants Burn rate modifier Metallic nano-catalysts Catalytic combustion Thermal decomposition

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Proximate Composition,Mineral Content and Fatty Acids Analyses of Aromatic and Non-Aromatic Indian Rice

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Rice science 2017年第1期24卷 21-31页

作者： Deepak kumar VERMA prem Prakash SRIVASTAV Agricultural and Food Engineering Department Indian Institute of TechnologyKharagpur 721302India

Awareness on nutritive value and health benefits of rice is of vital importance in order to increase the consumption of rice in daily diet of the human beings. In this study, a total of six aromatic and two non-aromatic rice accessions grown in India were analysed for their nutritional quality attributes including proximate composition, mineral contents and fatty acids. Data with three replications were used to measure Pearson＇s simple correlation co-efficient in order to establish the relationship among various nutritional quality attributes. The result on proximate composition showed that Govind Bhog had the highest moisture（13.57%） and fat（0.92%） content, which signifies its tasty attribute. Badshah Bhog exhibited the highest fibre content（0.85%）, carbohydrate content（82.70%） and food energy（365.23 k Cal per 100 g）. Among the minerals, the higher Ca（98.75 mg/kg）, Zn（17.00 mg/kg） and Fe（31.50 mg/kg） were in Gopal Bhog, whereas the highest Na（68.85 mg/kg） was in Badshah Bhog, the highest K（500.00 mg/kg） was in Swetganga, Khushboo and Sarbati. The highest contents of unsaturated fatty acids viz. oleic acid（49.14%）, linoleic acid（46.99%） and linolenic acid（1.27%） were found in Sarbati, whereas the highest content of saturated fatty acids viz. myristic acid（4.60%） and palmitic acid（31.91%） were found in Govind Bhog and stearic acid（6.47%） in Todal. The identified aromatic rice accessions Gopal Bhog, Govind Bhog and Badshah Bhog and non-aromatic rice accession Sarbati were found nutritionally superior among all eight tested accessions. The nutritional quality oriented attributes in this study were competent with recognized prominent aromatic and non-aromatic rice accessions as an index of their nutritional worth and recommend to farmers and consumers which may be graded as export quality rice with good unique nutritional values in international market.

关键词： aromatic unsaturated nutritional proximate accession carbohydrate oleic vital competent attribute

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Efficient Single-Stage Bridgeless AC to DC Converter Using Grey Wolf Optimization

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Computer Systems Science & Engineering 2022年第11期43卷 487-499页

作者： prema Kandasamy K.prem kumar Department of Electrical and Electronics Engineering Thangavelu Engineering CollegeChennai-600097India Department of Electrical and Electronics Engineering Rajalakshmi Engineering CollegeChennai-602105India

Bridgeless single-stage converters are used for efficient(alternative current)AC-(direct current)DC *** converters control generators,likeelectromagnetic meso-and micro-scale generators with low *** factorcorrection helps increase the factor of the power *** main advantage ofthe power factor is it shapes the input current for increasing the real power of theAC *** this paper,a two-switch bridgeless rectifier topology is designedwith a power factor correction *** the proposed converter topologyto have good power quality parameters,the closed loop scheme,which uses thegrey wolf optimization(GWO)algorithm,is *** successes ofGWO encourage this research to implement GWO in the *** performanceof the proposed topology is analyzed under different load *** is carried out using the MATLAB/Simulink environment,and theresults are compared with those of conventional(proportional integral derivative)PID and(particle swarm optimization)PSO *** validate the simulation results,a 350-W hardware prototype is implemented,and the voltage ripple,efficiency,and power factor under different load conditions are analyzed and *** comparative study clearly indicates that the proposed convertertopology with a closed loop control scheme using the GWO algorithm improves the power factor to 0.9732 and reduces the voltage ripple to 0.12%with a conversion efficiency of 98.25%.

关键词： Bridgeless AC converter DC converter GWO controller power factor

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Data with Non-Euclidean Geometry and Its Characterization

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Journal of Artificial Intelligence and Technology 2022年第1期2卷 3-8页

作者： prem kumar Singh Department of Computer Science and Engineering Gandhi Institute of Technology and Management-VisakhapatnamIndia

Recently,dealing with the non-Euclidean data and its characterization is considered as one of the major issues by *** first problem arises while defining the distinction among Euclidean and non-Euclidean geometry with its *** second problem arises while dealing with the non-Euclidean geometry in true,false,and uncertain *** third problem arises while investigating some patterns in non-Euclidean data *** paper focused on tackling these issues with some real-life examples in data processing,data visualization,knowledge representation,and quantum computing.

关键词： anisotropy Euclidean geometry heteroclinic orbit knowledge representation many-valued attributes non-Euclidean geometry

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Four-Way Turiyam Set-Based Human Quantum Cognition Analysis

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Journal of Artificial Intelligence and Technology 2022年第4期2卷 144-151页

作者： prem kumar Singh Department of Computer Science and Engineering Gandhi Institute of Technology and Management-VisakhapatnamAndhra Pradesh 530045India

Recently, the Turiyam set was introduced for characterization of data sets beyond true, false, and uncertain regionsbased on human cognition. This set is able to represent the unknown, undefined, or conduit metaphor of human quantumcognition precisely. One of the suitable examples is USA–Russia conflicts or Cold war is beyond the characterization of win,draw, or loss. It is totally based on the conduit metaphor of USA and Russia. In this case, a set of countries that may supportRussia (Sr) can be characterized as true regions. A set of countries that does not support Russia (i.e., supporting the USA) can becharacterized as false regions (Su). There is also a set of countries that supports both Russia–USA based on the given *** types of countries and their vote are uncertain. The fourth case is some countries like India, China, and UAE that choosenothing to fulfill their conduit metaphor. It is called Turiyam or four-dimension cognition. The characterization of this typeof four-dimension Turiyam cognition and its representation is one of the crucial tasks for data science researchers. It is indeed arequirement to understand the human quantum cognition and its conduit metaphor. To tackle this issue, the current paper will tryto introduce a method for characterization of this undefined, unknown, or Turiyam cognition via a defined interval set. Theobjective is to provide a way to explore them in known graph (t), not known graph (f), partial graph (i), or unknown graph (l) withan example.

关键词： fourth dimensions knowledge representation non-Euclidean Quaternion Turiyam set unknown

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A New High Performance Realization of Hyperchaotic Modified Canonical Chua Circuit Using JFETs

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Chinese Physics Letters 2008年第8期25卷 2803-2805页

作者： prem Bhushan Mital Umesh kumar R.S. Prasad IEC College of Engineering and Technology GB Nagar Pin-201 306 India Indian Institute of Technology Delhi Pin-110016 India Inderprastha Eng. College Sahibabad Ghaziabad (UP) India

A new implementation of hyperchaotic modified canonical Chua circuit using junction field-effect transistors （JFETs） is proposed. The design is based on a source coupled JFET circuit to approximate a smooth cubic nonlinearity and a two-terminal negative resistance element containing a p-n-p silicon transistor and an n-channel JFET. The realization is supported by Orcad Pspice simulation and numerical MATLAB results. The hyperchaotic nature is confirmed by two positive Lyapunov exponents associated with the attractor which is a fractal with a Lyapunov dimension between 3 and 4.

关键词： OSCILLATOR

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