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Exosomes derived from tumor adjacent fibroblasts efficiently target pancreatic tumors

Acta Pharmaceutica Sinica B 2024年第7期14卷 3009-3026页

作者： Saini Setua Shabia Shabir Poornima Shaji Ana martinez Bulnes Anupam Dhasmana Swathi Holla Nivesh K.mittal Nirakar Sahoo Tripti Saini Francesco Giorgianni mohammad Sikander Andrew E.massey Bilal B.Hafeez manish K.Tripathi Vincent P.Diego meena Jaggi Junming Yue Nadeem Zafar murali m.yallapu Stephen W.Behrman Sheema Khan Subhash C.Chauhan Department of Pharmaceutical Sciences College of Pharmacyand College of MedicineUniversity of Tennessee Health Science Center(UTHSC)MemphisTN 36163USA Department of Computer Science Islamic University of Science and TechnologyAwantiporaJ&K 192122India Department of Immunology and microbiology School of MedicineUniversity of Texas Rio Grande ValleyMcAllenTX 78504USA South Texas Center of Excellence in Cancer Research School of Medicinethe University of Texas Rio Grande ValleyMcAllenTX 78504USA Himalayan School of Biosciences and Cancer Research Institute Himalayan Institute of Medical SciencesSwami Rama Himalayan UniversityDehradun 248016India Plough Center for Sterile Drug Delivery Solutions UTHSCMemphisTN 38104USA Department of Biology College of SciencesUTRGVMcAllenTX 78539USA National Institute of Biomedical Imaging and Bioengineering(NIBIB) National Institutes of HealthBethesdaMD 20892USA South Texas Diabetes and Obesity Institute UTRGVMcAllenTX 78504USA Dept.of Laboratory medicine&Pathology University of WashingtonSeattleWA 98195USA Department of Surgery Baptist Memorial Medical EducationBaptist Memorial HospitalMemphisTN 38120USA Baptist Health Sciences University MemphisTN 38104USA

The application of extracellular vesicles,particularly exosomes(EXs),is rapidly expanding in the field of medicine,owing to their remarkable properties as natural carriers of biological *** study investigates utilization of exosomes derived from stromal cells of tumor adjacent normal tissues(NAF-EXs)for personalized medicine,which can be derived at the time of diagnosis by endoscopic ***,we show that exosomes(EXs)derived from NAFs demonstrate differential bio-physical characteristics,efficient cellular internalization,drug loading efficiency,pancreatic tumor targeting and delivery of ***-derived EXs(NAF-EXs)were used for loading ormeloxifene(ORm),a potent anti-cancer and desmoplasia inhibitor as a model *** found that ORm maintains normal fibroblast cell phenotype and renders them incompatible to be triggered for a CAF-like phenotype,which may be due to regulation of Ca^(2+) influx in fibroblast ***-EXs-ORm effectively blocked oncogenic signaling pathways involved in desmoplasia and epithelial mesenchymal transition(EmT)and repressed tumor growth in xenograft mouse *** conclusion,our data suggests preferential tropism of NAF-EXs for PDAC tumors,thus imply feasibility of developing a novel personalized medicine for PDAC patients using autologous NAF-EXs for improved therapeutic outcome of anti-cancer ***,it provides the opportunity of utilizing this biological scaffold for effective therapeutics in combination with standard therapeutic regimen.

关键词： Pancreatic cancer Tumor adjacent normal tissue fibroblasts(NAF) Desmoplasia Extracellular vesicles Exosomes Tumor targeting Ormeloxifene Personalized medicine

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Bioactive nanotherapeutic trends to combat triple negative breast cancer

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Bioactive materials 2021年第10期6卷 3269-3287页

作者： Pallabita Chowdhury Upasana Ghosh Kamalika Samanta meena Jaggi Subhash C.Chauhan murali m.yallapu Department of Pharmaceutical Sciences University of Tennessee Health Science CenterMemphisTNUSA Department of Biomedical Engineering School of EngineeringRutgers UniversityThe State University of New JerseyPiscatawayNJ08854USA Department of Immunology and microbiology School of MedicineUniversity of Texas Rio Grande ValleyMcAllenTXUSA South Texas Center of Excellence in Cancer Research School of MedicineUniversity of Texas Rio Grande ValleyMcAllenTXUSA

The management of aggressive breast cancer,particularly,triple negative breast cancer(TNBC)remains a formidable challenge,despite treatment *** newer therapies such as atezolizumab,olaparib,and sacituzumab can tackle the breast cancer prognosis and/or progression,but achieved limited survival benefit(s).The current research efforts are aimed to develop and implement strategies for improved bioavailability,targetability,reduce systemic toxicity,and enhance therapeutic outcome of FDA-approved treatment *** review presents various nanoparticle technology mediated delivery of chemotherapeutic agent(s)for breast cancer *** article also documents novel strategies to employ cellular and cell membrane cloaked(biomimetic)nanoparticles for effective clinical *** technologies offer a safe and active targeting nanomedicine for effective management of breast cancer,especially TNBC.

关键词： Breast cancer treatment Triple negative breast cancer Chemotherapy Nanoparticles membrane cloaked nanoparticles Nanomedicine Biomimetic nanoparticles

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milk exosomes:Nature’s abundant nanoplatform for theranostic applications

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Bioactive materials 2021年第8期6卷 2479-2490页

作者： Benilde Adriano Nycol m.Cotto Neeraj Chauhan meena Jaggi Subhash C.Chauhan murali m.yallapu Department of Immunology and microbiology School of MedicineThe University of Texas Rio Grande ValleyMcAllenTX78504USA South Texas Center of Excellence in Cancer Research School of MedicineUniversity of Texas Rio Grande ValleyMcAllenTX78504USA

Exosomes are a unique subpopulation of naturally occurring extracellular vesicles which are smaller intracellular membrane nanoparticle *** have proven to be excellent nanocarriers for carrying lipids,proteins,mRNAs,non-coding RNAs,and DNAs,and disseminating long-distance intercellular communications in various biological *** various cell-line or biological fluid derived exosomes,milk exosomes are abundant in nature and exhibit many nanocarrier characteristics favorable for theranostic *** be an effective delivery carrier for their clinical translation,exosomes must inbuilt loading,release,targeting,and imaging/tracking *** the unmet gaps of milk exosomes in theranostic technology it is essential to focus the current review on drug delivery and imaging *** review delineates the efficiency of exosomes to load therapeutic or imaging agents and their successful delivery *** is emphasized on possible modifications of exosomes towards increasing the stability and delivery of *** article also summarizes the specific applications and the process of developing milk exosomes as a future pharmaceutical drug delivery vehicle.

关键词： milk exosomes Extracellular vesicles Drug delivery Imaging agents Theranostic applications

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Development of polyvinylpyrrolidone/paclitaxel self-assemblies for breast cancer

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Acta Pharmaceutica Sinica B 2018年第4期8卷 602-614页

作者： Pallabita Chowdhury Prashanth K.B.Nagesh Sheema Khan Bilal B.Hafeez Subhash C.Chauhan meena Jaggi murali m.yallapu Department of Pharmaceutical Sciences and Center for Cancer Research University of Tennessee Health Science Center

The goal of this investigation was to develop and demonstrate a polymer/paclitaxel selfassembly(PTX-SA) formulation. Polymer/PTX-SAs were screened based on smaller size of formulation using dynamic light scattering analysis. Additionally, fluorescence microscopy and flow cytometry studies exhibited that polyvinylpyrrolidone(PVP)-based PTX-SAs(PVP/PTX-SAs) had superior cellular internalization capability in mCF7 and mDA-mB-231 breast cancer cells. The optimized PVP/PTXSAs exhibited less toxicity to human red blood cells indicating a suitable formulation for reducing systemic toxicity. The formation of PVP and PTX self-assemblies was confirmed using fluorescence quenching and transmission electron microscopy which indicated that the PVP/PTX-SAs were spherical in shape with an average size range of 53.81 nm as detected by transmission electron microscopy(TEm).FTIR spectral analysis demonstrates incorporation of polymer and paclitaxel functional groups in PVP/PTX-SAs. Both proliferation(mTS) and clonogenic(colony formation) assays were used to validate superior anticancer activity of PVP/PTX-SAs in breast cancer cells over paclitaxel. Such superior anticancer activity was also demonstrated by downregulation of the expression of pro-survival protein(Bcl-x L), upregulation of apoptosis-associated proteins(Bid, Bax, cleaved caspase 7, and cleaved PARP)and β-tubulin stabilization. These results support the hypothesis that PVP/PTX-SAs improved paclitaxel delivery to cancer cells.

关键词： Drug delivery Nanoparticles Self-assemblies Polymer Cancer therapeutics Breast cancer

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Electrochemical behavior of cerium(Ⅳ) in a RTIL and its mixture with ethanol

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Journal of Rare Earths 2014年第7期32卷 641-647页

作者： Arijit Sengupta m.S.murali P.K.mohapatra Radiochemistry Division Bhabha Atomic Research Centre

A systematic study was carried out to explore the electrochemical behavior of Ce in room temperature ionic liquid（CnmimBr, where n=6, 8, 10） and mixture of C6 mimBr and ethanol by cyclic voltammetry. With increase in the number of carbon atoms on the alkyl substituent on methyl imidazolium cation, the electrochemical window of the ionic liquids was found to extend towards more negative potential value, as a result there was a possibility of reduction of Ce to lower oxidation states. The diffusion coefficient and activation energy for the diffusion were calculated in all the ionic liquids and one of their mixtures with ethanol. With increase in n value, the diffusion coefficient of Ce decreased due to increase in viscosity of the medium while the activation energy for the diffusion followed a reverse trend for C6 mimBr, C8 mimBr and C10 mimBr, respectively. The observations indicated that the nature of species of Ce might be different in room temperature ionic liquids（RTILs） from that present in their mixtures with ethanol.

关键词： cerium cyclic voltammetry diffusion coefficient activation energy ethanol Cn mimBr (n=6, 8, 10) rare earths

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Control of BLDC motor using mRPID controller with modified landsman converter

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International Journal of Intelligent Computing and Cybernetics 2021年第4期14卷 664-685页

作者： murali Dasari A.Srinivasula Reddy m.Vijaya Kumar Electrical Engineering Jawaharlal Nehru Technological University AnantapuramuAnanthapurIndia CmR Engineering College SecunderabadIndiaand Electrical and Electronics Engineering Jawaharlal Nehru Technological University AnantapuramuAnanthapurIndia

Purpose-The principal intention behind the activity is to regulate the speed,current and commutation of the brushless DC(BLDC)***,the authors can control the ***/methodology/approach-In order to regulate the current and speed of the motor,the multiresolution PID(mRPID)controller is *** altered Landsman converter is utilized in this proposed suppression circuit,and the obligation cycle is acclimated to acquire the ideal DC-bus voltage dependent on the speed of the BLDC *** adaptive neuro-fuzzy inference system-elephant herding optimization(ANFISEHO)calculation mirrors the conduct of the procreant framework in ***-Brushless DC motor’s dynamic properties are created,noticed and examined by mATLAB/Simulink *** performance will be compared with existing genetic ***/value-The presented approach and performance will be compared with existing genetic algorithms and optimization of different structure of BLDC motor.

关键词： Brushless DC(BLDC)motors Elephant herding optimization(EHO) Adaptive neuro-fuzzy inference system(ANFIS) Landsman converter

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Computation of PoA for Selfish Node Detection and Resource Allocation Using Game Theory

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Computer Systems Science & Engineering 2023年第11期47卷 2583-2598页

作者： S.Kanmani m.murali Department of CSE SRM Institute of Science and TechnologyKattankulathur603203India Department of Computing Technologies SRM Institute of Science and TechnologyKattankulathur603203India

The introduction of new technologies has increased communication network coverage and the number of associating nodes in dynamic communication networks(DCN).As the network has the characteristics like decentralized and dynamic,few nodes in the network may not associate with other *** uncooperative nodes also known as selfish nodes corrupt the performance of the cooperative ***,the nodes cause congestion,high delay,security concerns,and resource *** study presents an effective selfish node detection method to address these *** Price of Anarchy(PoA)and the Price of Stability(PoS)in Game Theory with the Presence of Nash Equilibrium(NE)are discussed for the Selfish Node *** is a novel experiment to detect selfish nodes in a network using ***,the least response dynamic-based Capacitated Selfish Resource Allocation(CSRA)game is introduced to improve resource usage among the *** suggested strategy is simulated using the Solar Winds simulator,and the simulation results show that,when compared to earlier methods,the new scheme offers promising performance in terms of delivery rate,delay,and throughput.

关键词： Dynamic communication network(DCN) price of anarchy(PoA) nash equilibrium(NE) capacitated selfish resource allocation(CSRA)game game theory price of stability(PoS)

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Synthesis and characterization of AlCoCrCuFeZnx high-entropy alloy by mechanical alloying

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Progress in Natural Science:materials International 2016年第4期26卷 380-384页

作者： m.murali S.P.Kumaresh Babu B.Jeevan Krishna A.Vallimanalan Department of metallurgical and materials Engineering National Institute of Technology

Equi-atomic and non equi-atomic multi-component systems were synthesized through different routes to form high-entropy single solid solution. One such high-entropy alloy（HEA） with hexanary composition AlCoCrCuFeZnxwas synthesized using mechanical alloying. The effect of zinc variation on the crystal structure and phase formation was characterized using XRD, FESEm with EDS and TEm. The synthesis resulted in both equi-atomic and non equi-atomic nano crystalline AlCoCrCuFeZn with a crystallite size less than 10 nm.

关键词： High-entropy alloy mechanical alloying Crystallite size Lattice strain Selected area diffraction

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RAmAN SPECTROSCOPIC STUDY ON PREDICTION OF TREATmENT RESPONSE IN CERVICAL CANCERS

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Journal of Innovative Optical Health Sciences 2013年第2期6卷 63-70页

作者： S.RUBINA m.S.VIDYASAGAR C.murali KRISHNA Chilakapati Laboratory Advanced Centre for TreatmentResearch and Education in CancerTata Memorial Centre Kharghar 410210India Department of Radiotherapy and Oncology Shirdi Sai Baba Cancer Hospital Kasturba Medical College Manipal UniversityManipal 576104India

Concurrent chemoradiotherapy(CCRT)is the choice of treatment for locally adv anced cervical cancers;however,tumors exhibit diverse response to *** prediction of tumor response leads to individualizing treatment *** evaluation criteria in solid tumors(RECIST),the current modality of tumor response assessment,is often subject ive and carried out at the first visit after treatment,which is about four ***,there is a need for better predictive tool for *** spectroscopic techniques,sensitive to molecular alteration,are being pursued as potential diagnostic *** pilot study ains to explore the fiber-optic-based Raman spectroscopy approach in prediction of tumor response to CCRT,before taking up extensive in vivo *** vivo Raman spectra were acquired from biopsies collected from 11 normal(148 spectra),16 tumor(201 spectra)and 13 complete response(151 CR spectra),one partial response(8 PR spectra)and one nonresponder(8 NR spectra)*** was analyzed using principal component linear discriminant analysis(PC-LDA)followed by leave-one-out cross-validation(LOO-CV).Findings suggest that normal tissues can be efficiently classified from both pre-and post-treated tumor biopsies,while there is an overlap between pre-and post-CCRT tumor *** of CR,PR and NR tissues were subjected to principal component analysis(PCA)and a tendency of classification was observed,corroborating previous ***,this study further supports the feasibility of Raman spectroscopy in prediction of tumor radioresponse and prospective noninvasive in vivo applications.

关键词： Concurrent chemoradiotherapy tumor response principal component linear discriminant analysis principal component analysis response evaluation criteria in solid tumors

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STUDIES ON mOLECULAR WEIGHT DISTRIBUTION OF CARBON FIBER POLYmER PRECURSORS SYNTHESIZED USING mIXED SOLVENTS

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Chinese Journal of Polymer Science 2012年第5期30卷 664-673页

作者： G.Santhana Krishnan A.Burkanudeen N.murali Hemant Phadnis materials Science Division CSIRNational Aerospace LaboratoriesBangalore-560017India Post Graduate and Research Department of Chemistry Jamal Mohammed CollegeBharathidasan UniversityTiruchirappalliIndia malvern Application Laboratory Naimex HouseBangalore-560045India

The molecular weight distributions were estimated for carbon fiber polymer precursors such as poly（acrylonitrile-co-itaconic acid） synthesized by semi batch solution polymerization in mixed solvents media with the azonitrile compounds as initiator under the different ratios of solvent and non solvent from 0.75 to 2.5 in weight. The copolymer was characterized by using Fourier transform infrared spectroscopy （FTIR） and nuclear magnetic resonance （1H-NmR） analyses. The molecular weight distributions were evaluated by mv/mn ratios estimated from viscosity and osmotic measurements, and mw/mn estimated from size exclusion chromatography. The molecular weight distributions of these polymers as determined from m, Jmn and mw/mn are 2.9 to 3,2 and 2.0 to 2.5 respectively. The molecular distributions were close to a narrow distribution of 2.0 when the solvent/non-solvent ratio was varied between 1.4 and 2.0. Intrinsic viscosity [η] as a function of molecular weight of poly（acrylonitrile-co-itaconic acid） was evaluated by means of low angle laser light scattering with size exclusion chromatography （SEC-LALLS） and viscometry with SEC （SEC-VISCO）. The relationship between [η] and mw for poly（acrylonitrile-co-itaconic acid） in DmF at 50℃ was [q] = 1.1×10-5 mw0.79, where [η] is obtained in dL/g.

关键词： molecular weight distribution Size exclusion chromatography Osmometry Viscometry Polyacrylonitrilecopolyrner.

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