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Exosomes derived from tumor adjacent fibroblasts efficiently target pancreatic tumors

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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

Management of proximal tibial stress fracture associated with advanced knee osteoarthritis:A systematic review

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Chinese Journal of Traumatology 2024年第3期27卷 147-152页

作者： Mukesh Kumar Saini Mahendra Singh Devendra Singh Prem manohar Seervi Pera Jayavardhan Reddy Neelam Ramana Reddy Department of Orthopaedics Dr SN Medical CollegeJodhpur342011India Department of Orthopaedics Star HospitalsB Block Banjara HillsHyderabad500034India

Purpose:Tibial stress fracture associated with knee osteoarthritis is an unusual and difficult clinical *** is no clear existing treatment guideline for this uncommon clinical *** aim of this study is to review the impact of various treatment options for patients with advanced knee osteoarthritis associated with proximal tibial stress ***:The study was performed using the databases of PubMed and *** index for non-randomized studies score was used to evaluate the included studies’*** concluded data included the treatment approach,reported outcome measure,and time to fracture *** literature search was started in December 2021 and accomplished in January 2022.A narrative description of the different methods and comparison of their results were ***:Out of total assessed 69 studies,9 studies were included in our *** commonest treatment approach used was total knee arthroplasty by long tibial stem *** mean preoperative knee society score and knee functional score were 30.62 and 23.17,*** mean postoperative knee society knee score was 86.87,while the functional score was *** average reported time to achieve fracture union was 4 months(a range of 2.07-5.50 months).Conclusion:The optimal clinical outcome for treating either acute or mobile tibial stress fracture in patients with advanced knee osteoarthritis can be achieved with long stem total knee ***,due to heterogeneity of data,comparison of different treatment options for chronic proximal tibial stress fracture mal-union/non-union coexisting with knee osteoarthritic and such inferences need to be judged cautiously.

关键词： Tibial stress fracture Knee osteoarthritis Total knee arthroplasty

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

Elastic and Optoelectronic Properties of KCdF3:ab initio Calculations through LDA/GGA/Tb-mbJ within FP-LAPW Method

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Chinese Physics Letters 2015年第1期32卷 108-112页

作者： K. Ephraim babu N. murali K. Vijaya babu b. Kishore babu V. Veeraiah Modelling and Simulation in Materials Science Laboratory Department of Physics Andhra University Visakhapatnam 530003 Andhra Pradesh India Department of Engineering Chemistry A UCE(A) Andhra University Visakhapatnam 530003 Andhra Pradesh India

Ab initio calculations are performed on the electronic, structural, elastic and optical properties of the cubic per- ovskite KCdF3. Tile Kohn Sham equations are solved by applying the full potential linearized augmented plane wave （FP-LAPW） method. The exchange correlation effects are included through the local density approximation （LDA ）, generalized gradient approximation （GGA） and modified becke-Johnson （mbJ） exchange potential The calculated lattice constant is in good agreement with the experimental result. The elastic properties such as elastic constants, anisotropy factor, shear modulus, Young＇s modulus and Poisson＇s ratio are calculated. KCdF3 is ductile and elastically anisotropic. The calculations of the electronic band structure, density of states （DOS） and charge density show that this compound has an indirect energy band gap （M-F） with a mixed ionic and covalent bonding. The contribution of the different bands is analyzed from the total and partial density of states curves. Optical response of the dielectric functions, optical reflectivity, absorption coefficient, real part of optical conductivity, refractive index, extinction coefficient and electron energy loss, are presented for the energy range of O-40eV. The compound KCdF3 can be used for high-frequency optical and optoelectronic devices.

关键词： GGA Cd Elastic and Optoelectronic Properties of KCdF3:ab initio Calculations through LDA/GGA/Tb-mbJ within FP-LAPW Method LDA FP

Clinical and dietary predictors of common carotid artery intima media thickness in a population with type 1 and type 2 diabetes: A cross-sectional study

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World Journal of Diabetes 2017年第1期8卷 18-27页

作者： Kristina S Petersen Jennifer b Keogh Peter J Meikle manohar L Garg Peter M Clifton School of Pharmacy and Medical Sciences University of South Australia baker IDI Heart and Diabetes Institute Nutraceuticals Research Group University of NewcastleCallaghan

AIM To determine the clinical and dietary predictors of common carotid artery intima media thickness(CCA IMT) in a cohort of subjects with type 1 and type 2 diabetes. METHODS Participants with type 1(n = 23) and type 2 diabetes(n = 127) had mean and mean maximum CCA IMT measured using b mode ultrasound. Dietary intake was measured using a food frequency questionnaire. Clinical and dietary predictors of mean and mean maximum CCA IMT were determined using linear regression analysis adjusted for potential confounders. RESULTS The main predictors of mean and mean maximum CCA IMT were age and weight. After multivariate adjustment there were no dietary predictors of CCA IMT. However,in subjects that were not prescribed a lipid lowering medication alcohol consumption was positively associated with CCA IMT after multivariate adjustment. No difference existed in CCA IMT between subjects with type 1 or type 2 diabetes once age was adjusted for. CONCLUSION CCA IMT was predominantly predicted by age and weight in these subjects with diabetes. The finding that CCA IMT was not different between people with type 1 and type 2 diabetes warrants further investigation in a larger cohort.

关键词： Diabetes Carotid intima media thickness Arterial structure Diet Lipidomics Carotenoids

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

Diversity,Distribution and Prioritization of Fodder Species for Conservation in Kullu District,Northwestern Himalaya,India

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Journal of Mountain Science 2007年第3期4卷 259-274页

作者： S. S. Samant Man Singh manohar Lal Shreekar Pant G.b.Pant Institute of Himalayan Environment & Development Himachal UnitMohal-Kullu175 126Himachal PradeshIndia

In the Indian Himalayan Region predominantly rural in character, livestock is one of the main sources of livelihood and integral part of the economy. Livestock mostly rely on fodder from wild. The diversity, distribution, utilization pattern, nativity, endemism, rarity, seasonality of availability, nutritive values, perceived economic values and pressure use index of livestock have not been studied. The present study attempts to enumerate 150 species of fodder representing trees (51 spp.), shrubs (54 spp.) and herbs (45 spp.). Poaceae (19 spp.) and Fabaceae (13 spp.) amongst families and Salix (6 spp.), Ficus, Clematis, and Desmodium (5 spp., each) amongst genera are rich in species. Maximum species were found in the 1801 ~ 2600 m zone, and the remaining two zones showed relatively low diversity. Out of the 150 species, 109 are used in summer, 5 winter and 36 throughout year. During rainy season, mostly grasses are used as fodder. Only 83 species are native to the Himalayan region, one species, Strobilanthus atropuroureus is endemic and 35 species are near endemic. The nutritive values of the fodder species were reviewed, and economic values and status of the species were also assessed. The pressure use index of the species was calculated on the basis of cumulative values of the utilization pattern, altitudinal distribution, availability, status, nativity and endemism. Amongst the species, Grewia oppositifoilia, Morus serrata, Indigofera heterantha, Quercus leucotrichphora, Ulmus villosa, U. wallichiana and Aesculus indica showed highest PUI indicating high preference and pressure. Season wise prioritization of the species for different altitudinal zones has been done. Appropriate strategy and action plan have been suggested for the conservation and management of fodder species.

关键词： Diversity utilization native endemic nutritive and economic value pressure use index prioritization conservation Indian Himalayan Region

The role of Epstein-barr virus in multiple sclerosis:from molecular pathophysiology to in vivo imaging

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Neural Regeneration Research 2019年第3期14卷 373-386页

作者： Yi Guan Dejan Jakimovski murali Ramanathan bianca Weinstock-Guttman Robert Zivadinov buffalo Neuroimaging Analysis Center Department of Neurology Jacobs School of Medicine and Biomedical Sciences University at BuffaloState University of New York Jacobs Comprehensive MS Treatment and Research Center Department of Neurology Jacobs School of Medicine and Biomedical SciencesUniversity at Buffalo State University of New York Department of Pharmaceutical Sciences State University of New York Center for biomedical Imaging at Clinical Translational Science Institute University at Buffalo State University of New York

Multiple sclerosis(MS) is a disease of the central nervous system characterized by inflammation, demyelination, and neuronal damage. Environmental and genetic factors are associated with the risk of developing MS, but the exact cause still remains unidentified. Epstein-barr virus(EbV), vitamin D, and smoking are among the most well-established environmental risk factors in MS. Infectious mononucleosis, which is caused by delayed primary EbV infection, increases the risk of developing MS. EbV may also contribute to MS pathogenesis indirectly by activating silent human endogenous retrovirus-W. The emerging b-cell depleting therapies, particularly anti-CD20 agents such as rituximab, ocrelizumab, as well as the fully human ofatumumab, have shown promising clinical and magnetic resonance imaging benefit. One potential effect of these therapies is the depletion of memory b-cells, the primary reservoir site where EbV latency occurs. In addition, EbV potentially interacts with both genetic and other environmental factors to increase susceptibility and disease severity of MS. This review examines the role of EbV in MS pathophysiology and summarizes the recent clinical and radiological findings, with a focus on b-cells and in vivo imaging. Addressing the potential link between EbV and MS allows the better understanding of MS pathogenesis and helps to identify additional disease biomarkers that may be responsive to b-cell depleting intervention.

关键词： Epstein-barr virus multiple sclerosis meningeal inflammation magnetic resonance imaging leptomeningeal contrast enhancement mononucleosis human endogeneous retrovirus-W b-cells

Hericium Erinaceus (bull.:Fr.) Pers.,A Medicinal Mushroom,Activates Peripheral Nerve Regeneration

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Chinese Journal of Integrative Medicine 2016年第10期22卷 759-767页

作者： Kah-Hui Wong Gowri Kanagasabapathy murali Naidu Pamela David Vikineswary Sabaratnam Department of Anatomy Faculty of Medicine University of Malaya Mushroom Research Centre University of Malaya Institute of biological Sciences Faculty of Science University of Malaya

Objective： To study the ability of aqueous extract of Hericium erinaceus mushroom in the treatment of nerve injury following peroneal nerve crush in Sprague-Dawley rats. Methods： Aqueous extract of Hericium erinaceus was given by daily oral administration following peroneal nerve crush injury in Sprague- Dawley rats. The expression of protein kinase b （Akt） and mitogen-activated protein kinase （MAPK） signaling pathways; and c-Jun and c-Fos genes were studied in dorsal root ganglia （DRG） whereas the activity of protein synthesis was assessed in peroneal nerves by immunohistochemical method. Results： Peripheral nerve injury leads to changes at the axonal site of injury and remotely located DRG containing cell bodies of sensory afferent neurons. Immunofluorescence studies showed that DRG neurons ipsilateral to the crush injury in rats of treated groups expressed higher immunoreactivities for Ak＇t, MAPK, c-Jun and c-Fos as compared with negative control group （P〈0.05）. The intensity of nuclear ribonucleoprotein in the distal segments of crushed nerves of treated groups was significantly higher than in the negative control group （P〈0.05）. Conclusion： H. erinaceus is capable of promoting peripheral nerve regeneration after injury. Potential signaling pathways include Akt, MAPK, c-Jun, and c-Fos, and protein synthesis have been shown to be involved in its action.

关键词： Hericium erinaceus dorsal root ganglia signaling pathways gene expression protein synthesis machinery peripheral nerve regeneration