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Immunomodulatory oligonucleotide IMT504:Effects on mesenchymal stem cells as a first-in-class immunoprotective/immunoregenerative therapy

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World Journal of Stem Cells 2017年第3期9卷 45-67页

作者： Jorge Zorzopulos Steven M Opal Andrés Hernando-Insúa juan M Rodriguez Fernanda Elías juan Fló Ricardo A lópez Norma A Chasseing Victoria A lux-lantos Maria F Coronel Raul Franco Alejandro D Montaner David l Horn Immunotech S.A. Ciudad de Buenos Aires C1440FFXArgentina Infectious Disease Division Memorial Hospital of Rhode Island and Alpert Medical SchoolProvidenceRI 02905United States Fundación Pablo Cassara Ciudad Autonoma de Buenos Aires C1440FFXArgentina Instituto de Biología y Medicina Experimental(IBYME-CONICET) Ciudad Autónoma de Buenos Aires C1428ADNArgentina Instituto de Ciencia y Tecnolog'DR.Cesar Milstein” Fundación Pablo CassaráCiudad Autonoma de Buenos Aires C1440FFXArgentina David Horn llC DoylestownPA 18902United States

The immune responses of humans and animals to insults(i.e., infections, traumas, tumoral transformation and radiation) are based on an intricate network of cells and chemical messengers. Abnormally high inflammation immediately after insult or abnormally prolonged proinflammatory stimuli bringing about chronic inflammation can lead to life-threatening or severely debilitating diseases. Mesenchymal stem cell(MSC) transplant has proved to be an effective therapy in preclinical studies which evaluated a vast diversity of inflammatory conditions. MSCs lead to resolution of inflammation, preparation for regeneration and actual regeneration, and then ultimate return to normal baseline or homeostasis. However, in clinical trials of transplanted MSCs, the expectations of great medical benefit have not yet been fulfilled. As a practical alternative to MSC transplant, a synthetic drug with the capacity to boost endogenous MSC expansion and/or activation may also be effective. Regarding this, IMT504, the prototype of a major class of immunomodulatory oligonucleotides, induces in vivo expansion of MSCs, resulting in a marked improvement in preclinical models of neuropathic pain, osteoporosis, diabetes and sepsis. IMT504 is easily manufactured and has an excellent preclinical safety record. In the small number of patients studied thus far, IMT504 has been well-tolerated, even at very high dosage. Further clinical investigation is necessary to demonstrate the utility of IMT504 for resolution of inflammation and regeneration in a broad array of human diseases that would likely benefit from an immunoprotective/immunoregenerative therapy.

关键词： Immunohomeostasis Immunoprotection Immunoregeneration Inflammation Mesenchymal stem cells IMT504

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Pharmacokinetic evaluation of Shenfu Injection in beagle dogs after intravenous drip administration

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Acta Pharmaceutica Sinica B 2016年第6期6卷 584-592页

作者： Yuqiao Zhang Dali Tian Yuyou Huang ling li juan Mao juan Tian Jinsong Ding School of Pharmaceutical Sciences Central South University China Resources San-Jiu (Ya’an) Pharmaceutical Co. Ltd.

Shenfu Injection (SFI) is a well-defined Chinese herbal formulation that is obtained from red ginseng and processed aconite root. The main active constituents in SFI are ginsenosides and aconitum alkaloids. In this work, ginsenosides (ginsenoside Rg 1, ginsenoside Rbl and ginsenoside Rc) and aconitum alkaloids (benzoylmesaconine and fuziline) were used as the index components to explore the pharmacokinetic behavior of SFI. A selective and sensitive HPlC MS/MS method was developed for the quantification of ginsenosides and aconitum alkaloids in dog plasma and was used to characterize the pharmacokinetics of the five index components after intravenous drip of three different dosages of SFI in beagle dogs. The pharmacokinetic properties of the index components were linear over the dose range of 2-8 ml/kg. (C) 2016 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND

关键词： HPlC-MS/MS Ginsenoside Aconittun alkaloids Phammcokinetics Shenfu Injection Beagle dogs

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Expression and significance of p53 and mdm2 in patients with leukoplakia cancer

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Asian Pacific Journal of Tropical Medicine 2013年第10期6卷 831-834页

作者： juan-juan Cui Xiao-lan Han Wei-Min Wang Department of Stomatology the First Affiliated Hospital of Anhui Medical University

Objective:To study the relationship of the expressions of p53 and mdm2 in leukoplakia ***:RT-PCR was used to detect the mRNA of p53,mdm2 in patients with leukoplakia *** frequencies of p53,mdm2 in peripheral blood were detected by flow cytometric ***:The expression of p53mRNA in normal oral mucosa,simple oral leukoplakia,no-simple oral leukoplakia and leukoplakia cancer were 7.7%,27.3%,33.3%,56.8%,*** frequencies of p53 in normal oral mucosa,simple oral leukoplakia,no-simple oral leukoplakia and leukoplakia cancer were(0.3±0.1)%,(l.6±0.9)%,(1.9±1.1)%,(3.4±1.8)%.The expression of mdm2 mRNA in normal oral mucosa,simple oral leukoplakia,no-simple oral leukoplakia and leukoplakia cancer were 0.0%,6.8%,11.1%,37.8%,*** frequencies of mdm2 in normal oral mucosa,simple oral leukoplakia,no-simple oral leukoplakia and leukoplakia cancer were(0.1±0.1)%,(0.8±0.6)%,(1.2±0.8)%,(1.2±0.8)%.There was a positively correlation between p53 mRNA and mdm2 ***:The positive rate of p53 and mdm2 cells in the peripheral blood increases in patients with leukoplakia cancer tissue and has positive correlation with the severity of leukoplakia cancer.

关键词： Oral leukoplakia p53 mdm2 RT-PCR

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Downregulation of signal transduction and STAT3 expression exacerbates oxidative stress mediated by NlRP3 inflammasome

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Neural Regeneration Research 2018年第12期13卷 2147-2155页

作者： Hua Bai Qi-Fang Zhang juan-juan Duan De-Jun Yu li-Jie liu Medical laboratory Center Third Affiliated Hospital Guizhou Medical University Department of Neurology Third Affiliated Hospital Guizhou Medical University Key laboratory of Endemic and Ethnic Diseases of Ministry of Education and Key Laboratory of Medical Molecular Biology Guizhou Medical University

Activated nucleotide binding to the oligonucleotide receptor protein 3（NlRP3） inflammasome is possibly involved in the pathogenesis of Alzheimer＇s disease through oxidative stress and neurogenic inflammation. low expression of the signal transducer and activator of transcription 3（STAT3） gene may promote the occurrence of neurodegenerative diseases to some extent. To clarify the roles of the NlRP3 inflammasome and STAT3 expression in oxidative stress,（1） SHSY5 Y cells were incubated with 1 mM H2 O2 to induce oxidative stress injury, and the expression of human-cell-specific signal transduction, STAT3-shRNA silencing signal transduction and STAT3 were detected. Cells were pretreated with Ca2＋ chelator BAPATA-AM（0.1 mM） for 30 minutes as a control.（2） Western blot assay was used to analyze the expression of caspase-1, NlRP3, signal transduction and STAT3. Enzyme-linked immunosorbent assay was used to analyze interleukin-1β levels. Flow cytometry was carried out to calculate the number of apoptotic cells. We found that H2 O2 treatment activated NlRP3 inflammasomes and decreased phosphorylation of signal transduction and STAT3 serine 727. BAPTA-AM pretreatment abolished the H2 O2-induced activation of NlRP3 inflammasomes, caspase-1 expression, interleukin-1β expression and apoptosis in SHSY5 Y cells, and had no effect in cells with downregulated STAT3 expression by RNAi. The findings suggest that downregulation of signal transduction and STAT3 expression may enhance the oxidative stress mediated by NlRP3, which may not depend on the Ca2^＋ signaling pathway.

关键词： nerve regeneration signal transducer and activator of transcription 3 calcium caspase-l nucleotide binding to the oligonucleotide receptor protein 3 inflammasome hydrogen peroxide Alzheimer's disease shRNA SHSYSY cells neural regeneration

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Mechanically Robust Polylactide Fibers with Super Heat Resistance via Constructing in situ Nanofibrils

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Chinese Journal of Polymer Science 2023年第6期41卷 962-971,I0011页

作者： Jun lu li-Xiang Yi Yong-Huan Zhao Yang Meng Peng-Xiang Yu juan-juan Su Jian Han College of Materials and Textiles Zhejiang Sci-Tech UniversityHangzhou 310018China The Key lab of Industrial Textile Material and Manufacturing Technology Zhejiang ProvinceZhejiang Sci-Tech UniversityHangzhou 310018China

All-PlA fibers with excellent comprehensive performance and recycling convenience are realized *** molecular weight poly(D-lactide)(HPDlA)is incorporated into poly(l-lactide)(PllA)matrix to construct in situ nanofibrils structure by taking advantages of the microphase separation between HPDlA and *** tensile strength of HPDlA/PllA composite fibers(HDl-8)is enhanced from 2.1 cN/dtex of neat PllA-8 fibers up to 2.9 cN/*** boiling water shrinkage(BWS)and shrinkage in hot air(HAS)significantly decrease to 7.8%and 2.8%,*** abundance of in situ nanofibrils creates a grille-like structure that is crucial for both heat and hydrolysis *** strikingly,a hybrid shish-kebab structure induced by the in situ nanofibrils serves as a mechanical *** work paves a new way for heat resistance and self-reinforcement modification of PlA materials.

关键词： materials. fibers lactide

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Preliminary Retrieval of Aerosol Optical Depth from All-sky Images

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Advances in Atmospheric Sciences 2010年第2期27卷 421-426页

作者：霍娟吕达仁 Key laboratory for Atmosphere and Global Environment Observation Chinese Academy of Sciences

The relationship between the radiance ratio （radiance at wavelength 450 nm to 650 nm） and aerosol optical depth （AOD） is analyzed in this paper by numerical simulation and a ＂lUT＂（look-up table） approach is then presented for the retrieval of AOD from the radiance ratio. In this lUT approach, the AOD retrieval error depends mainly on the assumption of aerosol types. From the preliminary simulation, a typical error of 15%–20% in AOD obtained from the radiance ratio is estimated, due to neglecting changes in the ground albedo and background atmosphere. At its worst, the AOD error reached a maximum of around 50%, which will be refined in the future. In the latter part of the paper, comparisons are made between AOD from the imager and from the CE-318 sun photometer, both located at Xianghe observatory in Hebei Province （39.75° N, 116.96° E）. This field experiment shows that AOD from the imager is highly correlated with AOD from the sun photometer, with a correlation coefficient of 0.95 and an average retrieval error of around 7%. A contrast experiment confirms the feasibility of retrieving AOD from all-sky images, but more analysis and future research are required to improve the accuracy.

关键词： all-sky image aerosol AOD radiance ratio

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Analysis and Improvement of an Efficient Controlled Quantum Secure Direct Communication and Authentication Protocol

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Computers, Materials & Continua 2018年第12期57卷 621-633页

作者： Jifeng Zhong Zhihao liu juan Xu Navigation College Jimei UniversityXiamen361021China School of Computer Science and Engineering Southeast UniversityNanjing211189China Key laboratory of Computer Network and Information Integration Southeast UniversityMinistry of EducationNanjing211189China Institute for Quantum Computing University of WaterlooWaterlooONCanadaN2L3G1

The controlled quantum secure direct communication(CQSDC)with authentication protocol based on four particle cluster states via quantum one-time pad and local unitary operations is *** is found that there are some serious security issues in this *** eavesdropper(Eve)can eavesdrop on some information of the identity strings of the receiver and the controller without being detected by the selective-CNOT-operation(SCNO)*** the same attack,Eve can also steal some information of the secret message that the sender *** addition,the receiver can take the same kind of attack to eavesdrop on some information of the secret message out of the control of the *** means that the requirements of CQSDC are not *** last,we improve the original CQSDC protocol to a secure one.

关键词： Quantum cryptography controlled quantum secure direct communication selective-CNOT-operation attack

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local Discontinuous Galerkin Method for Parabolic Interface Problems

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Acta Mathematicae Applicatae Sinica 2015年第2期31卷 453-466页

作者： Zhi-juan ZHANG Xi-jun YU Department of Mathematics Nanchang University laboratory of Computational Physics Institute of Applied Physics and Computational Mathematics

In this paper, the minimal dissipation local discontinuous Galerkin method is studied to solve the parabolic interface problems in two-dimensional convex polygonal domains. The interface may be arbitrary smooth curves. The proposed method is proved to be l2 stable and the order of error estimates in the given norm is O（h｜logh｜^1/2）. Numerical experiments show the efficiency and accuracy of the method.

关键词： parabolic interface problem minimal dissipation local discontinuous Galerkin method error estimates

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Chaetocin reactivates the lytic replication of Epstein-Barr virus from latency via reactive oxygen species

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Science China(life Sciences) 2017年第1期60卷 66-71页

作者： Shilun Zhang juan Yin Jiang Zhong Department of Microbiology and Microbial Engineering School of Life Sciences Fudan University Shanghai 200438 China

Oxidative stress, regarded as a negative effect of free radicals in vivo, takes place when organisms suffer from harmful stimuli. Some viruses can induce the release of reactive oxygen species （ROS） in infected cells, which may be closely related with their pathogenicity. In this report, chaetocin, a fimgal metabolite reported to have antimicrobial and cytostatic activity, was studied for its effect on the activation of latent Epstein-Barr virus （EBV） in B95-8 cells. We found that chaetocin remarkably up-regulated EBV lytic transcription and DNA replication at a low concentration （50 nmol l-l）. The activation of latent EBV was accompanied by an increased cellular ROS level. N-acetyl-l-cysteine （NAC）, an ROS inhibitor, suppressed chaetocin-induced EBV activation. Chaetocin had little effect on histone H3K9 methylation, while NAC also significantly reduced H3K9 methylation. These results suggested that chaetocin reactivates latent EBV primarily via ROS pathways.

关键词： Epstein-Barr virus reactive oxygen species chaetocin

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A Note on list Edge and list Total Coloring of Planar Graphs without Adjacent Short Cycles

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Acta Mathematica Sinica,English Series 2014年第1期30卷 91-96页

作者： Hui juan WANG Jian liang WU School of Mathematics Shandong University

letGbe a planar graph with maximum degreeΔ.In this paper,we prove that if any4-cycle is not adjacent to ani-cycle for anyi∈{3,4}in G,then the list edge chromatic numberχl（G）=Δand the list total chromatic number... 详细信息

关键词： list edge coloring list total coloring planar graph cycle

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