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Anti-cancer effects of sitagliptin,vildagliptin,and exendin-4 on triple-negative breast cancer cells via mitochondrial modulation

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BIOCELL 2022年第12期46卷 2645-2657页

作者： POOJA JAISWAL VERSHA TRIPATHI ANSHUL ASSAIYA DHARMENDRA KASHYAP RAHUL DUBEY ANAMIKA SINGH JANESH kumar HEM CHANDRA JHA rajesh SHARMA AMIT kumar DIXIT HAMENDRA SINGH PARMAR School of Biotechnology Devi Ahilya UniversityIndore452001India Laboratory of Membrane Protein Biology National Centre for Cell SciencePune411007India Department of Biosciences and Biomedical Engineering Indian Institute of TechnologyIndore452020India Department of Biotechnology IPS AcademyIndore452012India School of Pharmacy Devi Ahilya UniversityIndore452001India Central Council for Research in Ayurvedic Sciences Kolkata263645India

Triple-negative breast cancer(TNBC)cell line MDA-MB-231 is known for Warburg metabolism and defects in *** the other hand,dipeptidyl peptidase-IV(DPP-IV)inhibitors such as sitagliptin and vildagliptin and GLP-1 agonist exendin-4 are known to improve mitochondrial functions as well as biogenesis,but no study has evaluated the influence of these drugs on mitochondrial biogenesis on metastatic breast cancer cell *** have recently reported anticancer effects of 5-aminoimidazole-4-carboxamide riboside on MDA-MB-231 cells via activation of AMP-dependent kinase(AMPK),which activates the downstream transcription factors PGC-1α,PGC-1β,or FOXO1 for mitochondrial biogenesis;above-mentioned incretin-based therapies are also known to activate *** study evaluated the effects of sitagliptin,vildagliptin,and exendin-4 on MDA-MB-231 cells and the underlying changes in mitochondrial biogenesis,were *** with sitagliptin(100μM),vildagliptin(100μM),and exendin-4(10 nM)for 72 h to MDA-MB-231 cells led to a decrease in viability indicated by MTT assay,cell migration by scratch,and transwell migration assays,accompanied with marginal reduction in cell numbers along with the apoptotic appearance,the rate of apoptosis,and decreased lactate content in conditioned *** changes in the cancer phenotype were accompanied by an increase in the mitochondrial DNA to nuclear DNA ratio,increased MitoTracker green and red staining,and increased expression of transcription factors PGC-1α,NRF-1,NRF-2,TFAM,and ***-treatment of cells with these incretin-based drugs followed by 48 h treatment with 1μM doxorubicin increased doxorubicin sensitivity as observed by a decrease in viability by MTT ***,sitagliptin,vildagliptin,and exendin-4 exert their beneficial effects on TNBC cells via an increase in mitochondrial biogenesis that helps to switch Warburg metabolism into anti-Warburg *** response was in the order of:sitagliptin>vildagliptin>ex

关键词： Sitagliptin Vildagliptin Exendin-4 Apoptosis Migration Viability Chemo-sensitivity Mitochondrial biogenesis

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Oxidative Stressand Antioxidant Responses in Young Leaves of Mulberry Plants Grown Under Nitrogen, Phosphorus or Potassium Deficiency

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Journal of Integrative Plant Biology 2007年第3期49卷 313-322页

作者： rajesh kumar Tewari Praveen kumar Parma Nand Sharma Department of Botany University of LucknowLucknow226007India

The aim of this study was to associate the generation of reactive oxygen species （ROS） with Induced antloxidant responses and disturbed cellular redox environment in the nitrogen-（N）, phosphorus-（P）, or potassium-（K） deftcient mulberry （Morus alba L. var. Kanva-2） plants. The indicators of oxidative stress and cellular redox environment and antioxldant defense-related parameters were analyzed. Oeficlency of N, P or K suppressed growth, accelerated senescence, and decreased concentrations of chloroplastic pigments and glutathione. Lipid peroxidation and activities of superoxide dismutase, ascorbate peroxidase and glutathione reductase were also increased in these N, P, or K deprived plants. Concentration of hydrogen peroxide Increased in plants deficient in N or P. Oeficlency of N or P particularly altered the cellular redox environment as indicated by changes in the redox couples, namely ascorbic acid/total ascorbate decreased in P-, glutathione sulfydryl/total glutathione decreased in N-, and Increased in P-deficient plants. Activity staining of native gels for superoxide dismutase revealed Increased activity as Indicated by Increased intensity of bands, and induction of few new isoforms in P- and K-deficient plants. Oifferences in the patterns of superoxide dismutase isoforms and redox status （ascorbic acid/total ascorbate and glutathlone sulfydryl/total glutathione） Indicate that N-, P-, or K-deficiency altered antioxidant responses to varying extents in mulberry plants.

关键词： antioxidants potassium-deficiency lipid peroxidation Morus alba mulberry nitrogen-deficiency oxidative stress phosphorus-deficiency reactive oxygen species

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A New Exponential Fuzzy Entropy of Order-(α,β)and its Application in Multiple Attribute Decision-Making Problems

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Communications in Mathematics and Statistics 2017年第2期5卷 213-229页

作者： rajesh Joshi Satish kumar Department of Mathematics Maharishi Markandeshwar University MullanaAmbala 133207India

Fuzzy entropy is an important concept to measure the fuzzy *** of fuzziness of a fuzzy set is the measure of its *** the present communication,we have defined an exponential fuzzy entropy of order-(α,β).Besides establishing the validity of the proposed measure,we have also discussed some of its *** last,we have given the application of the proposed measure in multiple attribute decision-making *** this section,we have considered two cases for the weights of attributes:One is the case when weights are completely unknown to us,and the other is the case when weights are partially known to us.

关键词： Exponential entropy Fuzzy set Fuzzy entropy Exponential fuzzy entropy MADM

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Gastroprotective effect of Acacia nilotica young seedless pod extract:Role of polyphenolic constituents

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Asian Pacific Journal of Tropical Medicine 2012年第7期5卷 523-528页

作者： Vijay kumar Bansal rajesh kumar Goel Department of Pharmaceutical Sciences NIMS UniversityJaipurIndia Department of Pharmaceutical Sciences and Drug Research Punjabi University PatialaIndia

Objective:To systematically evaluate antiulcer potential of Acacia nilotica in different ulcer models in ***:Different extracts[ethanolie,50%hydroethanolic(50:50),70% hydroethanolic(70:30) and aqueous]of young seedless pods were examined in pylorus ligation induced gastric ulcers in *** parameters like,volume of gastric acid secretion,pH,free acidity,total acidity,ulcer index,mucin content and antioxidant studies were determined and were compared between extract treated,standard and vehicle control following ulcer induction. The most active extract was also evaluated in swimming stress induced and NSAID induced gastric ***:Among different extracts of young seedless pods only hydroethanolic extracts showed significant antiulcer activity in pyloric ligation induced *** more the 70%hydroethanolic extract showed better protection as compared to 50%hydroethanolic *** 70%hydroethanolic extract also showed significant mucoprotection in swimming stress induced and nonsteroidal antiinflammatory drugs induced gastric ***: The results of present study concluded that the hydroethanolic extract of young seedless pods of Acacia nilotica has antiulcer activity in pylorus ligation,swimming stress and NSAID induced rat ulcer *** extract containing more amount of phenolic components show high antiulcer activity,indicating the phenolic component of the extract to be responsible for the activity of the extracts.

关键词： Peptic ulcer Acacia nilotica Ulcer index Tannins Flavonoids

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Physics design of 14 MeV neutron generator facility at the Institute for Plasma Research

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Plasma Science and Technology 2023年第12期25卷 115-121页

作者： H L SWAMI S VALA M RAJPUT M ABHANGI Ratnesh kumar A SAXENA rajesh kumar Institute for Plasma Research Gandhinagar 382428India Homi Bhabha National Institute Training School ComplexMumbai 400094India

A high energy and high yield neutron source is a prime requirement for technological studies related to fusion reactor development. It provides a high-energy neutron environment for small-scale fusion reactor components research and testing such as tritium breeding, shielding, plasmafacing materials, reaction cross-section data study for fusion materials, etc. Along with ITER participation, the Institute of Plasma Research, India is developing an accelerator-based 14 MeV neutron source with a yield of 10^(12)n s^(-1). The design of the source is based on the deuterium–tritium fusion reaction. The deuterium beam is accelerated and delivered to the tritium target to generate 14 MeV neutrons. The deuterium beam energy and tritium availability in the tritium target are the base parameters of the accelerator-based neutron source design. The paper gives the physics design of the neutron generator facility of the Institute for Plasma Research. It covers the requirements, design basis, and physics parameters of the neutron generator. As per the analytical results generator can produce more than 1 × 10^(12)n s^(-1)with a 110 keV D^(+) ion beam of 10 mA and a minimum 5 Ci tritium target. However, the detailed simulation with the more realistic conditions of deuteron ion interaction with the tritium titanium target shows that the desired results cannot be achieved with 110 keV. The safe limit of the ion energy should be 300 keV as per the simulation. At 300 keV ion energy and 20 mA current, it reaches 1.6 × 10^(12)n s^(-1). Moreover, it was found that to ensure sufficiently long operation time a tritium target of more than 20 Ci should be used. The scope of the neutron source is not limited to the fusion reactor research studies, it is extended to other areas such as medical radioisotopes research, semiconductor devices irradiations, and many more.

关键词： neutron generator neutronics accelerator physics design nuclear fusion

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中国东北大地幔楔间断面结构的接收函数成像研究

中国东北大地幔楔间断面结构的接收函数成像研究

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作者： kumar rajesh 吉林大学

学位级别：硕士

东北亚是指从中国东北一直延伸到朝鲜半岛、日本、蒙古等地的亚洲地理区域。其在漫长而曲折的历史时期经历了许多不同的地质发展和演化阶段。古元古代初期,东北亚处于大陆边缘。中晚元古代时期,东北亚板块碰撞造山运动开始。在中生代时... 详细信息

东北亚是指从中国东北一直延伸到朝鲜半岛、日本、蒙古等地的亚洲地理区域。其在漫长而曲折的历史时期经历了许多不同的地质发展和演化阶段。古元古代初期,东北亚处于大陆边缘。中晚元古代时期,东北亚板块碰撞造山运动开始。在中生代时期,东北亚的海平面急剧下降,这与地震、火山活动的增加和大量大型金属矿床的形成相吻合。在整个古近纪时期,构造演化和火山喷发再次影响了东北亚,从而塑造了我们今天所了解的这个地区。本研究利用2009-2011年127个NECESSArray地震台网记录的高质量波形数据计算得到了研究区内P波接收函数,从而对东北亚壳幔间断面的性质有了更深入的认识。用于进行观测的34,060个接收函数是从646个远震事件的记录中获得的。为了确定各测点下的平均地壳厚度(H)和P/S波的波速比,本研究采用了H-k叠加技术。H-k叠加方法假设地壳介质是均匀的,根据预测的相对于直达P波的延迟时间,搜索得到能量最强的直达Ps震相和莫霍面的Pp Ps、Ps Ps和Ps Ps+Pp Ss等多次反射波。为了在每个深度对接收函数振幅进行叠加,并根据所选择的背景速度模型计算转换震相的射线路径和走时,可以利用CCP叠加将时间域接收函数映射到起伏的间断面上。本研究结果显示松辽盆地部分地区的地壳很薄,很可能与白垩纪时期盆地形成有关。这些位置的较薄的地壳证实了前人研究中推测的地幔上升流的可能性,而松辽盆地东部边界也存在大量的中新生代火山活动。在大兴安岭地区,莫霍面深度约为37km,而大兴安岭重力梯度带下方莫霍面厚度变化约4km。松辽盆地下方莫霍面最浅的区域对应郯庐断裂带的位置,这一现象是本研究显著的特征。莫霍面的复杂结构,尤其在郯庐断裂带下方存在5km左右的变化,表明断裂可能延伸到上地幔,可能与在那个时期发生的局部地幔隆升相关。本研究结果表明,莫霍面减薄与松辽盆地白垩系广泛发育的断裂形成过程相一致。CCP叠加结果显示,在123-129°E之间,地幔过渡带增厚了约35km。这一发现与前人通过P波层析成像在地幔转换带中发现停滞的太平洋板块的研究结果一致。Moho界面和LAB深度在不同的地区中有所不同。而在松辽盆地中部莫霍面最厚、LAB最浅,这两个不连续面深度相对连续。除了“CC”剖面外,124°E-125°E之间的区域发生显著变化,LAB达到最深。松辽盆地与三江盆地、二连盆地与海拉尔盆地的地壳厚度差异表明这些盆地的形成过程与机制可能不同。大兴安岭地区最南端莫霍面较浅,与以往地震资料一致,表明该地区较高的起伏可能受到地幔流上涌的动力支撑。松辽盆地下方莫霍面深度由东南向西北逐渐增大。松辽盆地北部沉积层增厚,地壳明显厚于盆地南部。松辽盆地地壳的Vp/Vs值略高于周围地区,但并不显著。此外,地质证据表明,晚侏罗世和晚白垩世都发生了地幔热物质上升。随着热物质的上升,大陆地壳穹顶抬升了2-3km,导致大量正断层形成。松辽盆地下方的这些特征表明地幔热流促进了地壳变薄以及后续的基性和超基性地壳的形成。地震层析成像显示长白山下方410km深处表现为低速异常区,地幔转换带呈现明显的高速异常。接收函数研究清楚地揭示了660km间断面显著的特征,与地震层析成像结果获得的构造异常相互印证。从40°N延伸到45.5°N北部,表现为较集中的大而缓的凹陷。随着进入松辽盆地,逐渐呈现弧形特征。410km和660km深度间断面厚度变化差异显著,地幔转换带在(40°N,130°E)顶界面深度只有410km。地幔转换带410km间断面最深处位于42°N,125°E到130°E之间。此外,在长白山火山以西约200km处,间断面发生了适当的抬升。

关键词：东北亚接收函数大地幔楔地幔转换带共转换点 H-k叠加

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Perturbing tumor cell metabolism with a Ru(Ⅱ)photo-redox catalyst to reverse the multidrug resistance of lung cancer

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Science China Chemistry 2023年第5期66卷 1482-1488页

作者： Siqi Wei Hui Liang Anyi Dao Yuzhen Xie Fengshu Cao Qingyan Ren Ashish kumar Yadav rajesh Kushwaha Arif Ali Mandal Samya Banerjee Pingyu Zhang Shaomin Ji Huaiyi Huang School of Pharmaceutical Science(Shenzhen)Shen Zhen Campus of Sun Yat-sen University Shenzhen 518107China Light Industry and Chemical Engineering College Guangdong University of TechnologyGuangzhou 510006China College of Chemistry and Environmental Engineering Shenzhen UniversityShenzhen 518060China Department of Chemistry Indian Institute of Technology(BHU)Varanasi UP-221005India

The novel concept of enzyme photocatalysis has recently attracted much attention in developing anticancer ***,the relationship between coenzyme depletion and cellular metabolomic changes has rarely been ***,we report the rational design of a deep-red light-triggered bis-tridentate Ru(Ⅱ)photocatalyst(Ru3),which induces cell metabolism disorder to combat multidrug ***3 exhibits promising multiple triplet excited states,a long lifetime,and high photocatalytic activity toward the ***,Ru3 shows high phototherapeutic activity(photo index=191–833)against diverse resistant(cisplatin,5-fluorouracil,or paclitaxel)lung cancer cells by inhibiting cellular peptide,lipid,and glycerophospholipid *** believe that cell metabolism inhibition by photo-redox catalysts is an effective form of therapeutics for drug-resistant cancer cells.

关键词： drug resistance photocatalytic therapy Ru(Ⅱ)photocatalyst NADPH cell metabonomic

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Zinc Oxide Nanostructures for NO_2 Gas–Sensor Applications:A Review

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Nano-Micro Letters 2015年第2期7卷 97-120页

作者： rajesh kumar O.Al-Dossary Girish kumar Ahmad Umar PG Department of Chemistry JCDAV College Department of Physics King Saud University Department of Chemistry Faculty of Arts and Sciences Najran University Promising Centre for Sensors and Electronic Devices (PCSED) Najran University

Because of the interesting and multifunctional properties,recently,ZnO nanostructures are considered as excellent material for fabrication of highly sensitive and selective gas ***,ZnO nanomaterials are widely used to fabricate efficient gas sensors for the detection of various hazardous and toxic *** presented review article is focusing on the recent developments of NO2gas sensors based on ZnO *** review presents the general introduction of some metal oxide nanomaterials for gas sensing application and finally focusing on the structure of ZnO and its gas sensing *** gas sensing characteristics such as gas response,response time,recovery time,selectivity,detection limit,stability and recyclability,etc are also discussed in this ***,the utilization of various ZnO nanomaterials such as nanorods,nanowires,nano-micro flowers,quantum dots,thin films and nanosheets,etc for the fabrication of NO2gas sensors are also ***,various factors such as NO2concentrations,annealing temperature,ZnO morphologies and particle sizes,relative humidity,operating temperatures which are affecting the NO2gas sensing properties are discussed in this ***,the review article is concluded and future directions are presented.

关键词： ZnO nanostructure Gas sensors Sensor parameters Sensor mechanism

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In vitro and in vivo anticancer potential and molecular targets of the new colchicine analog ⅢM-067

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Journal of Integrative Medicine 2023年第1期21卷 62-76页

作者： Sumera Malik Mubashir J.Mintoo Chilakala Nagarjuna Reddy rajesh kumar Pankul Kotwal Sandip BBharate Utpal Nandi Dilip M.Mondhe Sanket K.Shukla Pharmacology Division Council of Scientific and Industrial Research(CSIR)-Indian Institute of Integrative MedicineJammu 180001Jammu&KashmirIndia Academy of Scientific&Innovative Research(AcSIR) Ghaziabad 201002Uttar PradeshIndia Medicinal Chemistry Division CSIR-Indian Institute of Integrative MedicineJammu 180001Jammu&KashmirIndia Pharmacokinetics-Pharmacodynamics(PK-PD) Toxicology DivisionCSIR-Indian Institute of Integrative MedicineJammu 180001Jammu&KashmirIndia

Objective: The current study evaluated various new colchicine analogs for their anticancer activity and to study the primary mechanism of apoptosis and in vivo antitumor activity of the analogs with selective anticancer properties and minimal toxicity to normal ***: Sulforhodamine B(SRB) assay was used to screen various colchicine analogs for their in vitro cytotoxicity. The effect of N-[(7S)-1,2,3-trimethoxy-9-oxo-10-(pyrrolidine-1-yl)5,6,7,9-tetrahydrobenzo[a] heptalene-7-yl] acetamide(ⅢM-067) on clonogenicity, apoptotic induction, and invasiveness of A549 cells was determined using a clonogenic assay, scratch assay, and staining with 4’,6-diamidino-2-phenylindole(DAPI) and annexin V/propidium iodide. Mitochondrial membrane potential(MMP) and reactive oxygen species(ROS) levels were observed using fluorescence microscopy. Western blot analysis was used to quantify expression of proteins involved in apoptosis, cell cycle, and phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)/mammalian target of rapamycin(mTOR) signaling. Pharmacokinetic and in vivo efficacy studies against Ehrlich ascites carcinoma(EAC) and Ehrlich solid tumor models were conducted using Swiss albino ***: ⅢM-067 showed potent cytotoxicity and better selectivity than all other colchicine analogs screened in this study. The selective activity of ⅢM-067 toward A549 cells was higher among other cancer cell lines,with a selectivity index(SI) value of 2.28. ⅢM-067 demonstrated concentration-and time-dependent cytotoxicity against A549 cells with half-maximal inhibitory concentration values of 0.207, 0.150 and0.106 μmol/L at 24, 48 and 72 h, respectively. It also had reduced toxicity to normal cells(SI > 1) than the parent compound colchicine(SI = 1). ⅢM-067 reduced the clonogenic ability of A549 cells in a dose-dependent manner. ⅢM-067 enhanced ROS production from 24.6% at 0.05 μmol/L to 82.1% at 0.4 μmol/L and substantially decreased the MMP(100% in control to 5.6% at 0.4 μmol

关键词： Colchicine 1IIM-067 Apoptosis Antineoplastic agents Carcinoma Ehrlich tumor A549 cells

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Intermediate Energy Coulomb Excitation of Neutron-Rich Nuclei

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Chinese Physics Letters 2010年第3期27卷 104-107页

作者： Rajiv kumar rajesh Kharab H. C. Sharma Department of Applied Sciences Haryana College of Technology and Management Kaithal-136027 India Department of Physics Kurukshetra University Kurukshetra-136119 India

We reinvestigate the collective effects of the retardation as well as the bending on the Coulomb excitation cross sections and also on the B（E2） strengths of some neutron-rich isotopes using the intermediate energy Coulomb excitation theory. It is found that the B（E2） strengths extracted from the experimental Coulomb excitation cross section data get suppressed approximately by 6%. Furthermore, the obtained B（E2） strengths in the energy range 30-100 MeV/A are found to be in better agreement with the corresponding values known from other sources, than those obtained by using the recoil-corrected relativistic Coulomb excitation theory.

关键词： Nuclear physics

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