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Now showing items 1 - 16 of 25

  • Sp9 Regulates Medial Ganglionic Eminence-Derived Cortical Interneuron Development

    Liu, Zhidong   Zhang, Zhuangzhi   Lindtner, Susan   Li, Zhenmeiyu   Xu, Zhejun   Wei, Song   Liang, Qifei   Wen, Yan   Tao, Guangxu   You, Yan   Chen, Bin   Wang, Yanling   Rubenstein, John L.   Yang, Zhengang  

    Immature neurons generated by the subpallial MGE tangentially migrate to the cortex where they become parvalbumin-expressing (PV+) and somatostatin (SST+) interneurons. Here, we show that the Sp9 transcription factor controls the development of MGE-derived cortical interneurons. SP9 is expressed in the MGE subventricular zone and in MGE-derived migrating interneurons. Sp9 null and conditional mutant mice have approximately 50% reduction of MGE-derived cortical interneurons, an ectopic aggregation of MGE-derived neurons in the embryonic ventral telencephalon, and an increased ratio of SST+/PV+ cortical interneurons. RNA-Seq and SP9 ChIP-Seq reveal that SP9 regulates MGE-derived cortical interneuron development through controlling the expression of key transcription factors Arx, Lhx6, Lhx8, Nkx2-1, and Zeb2 involved in interneuron development, as well as genes implicated in regulating interneuron migration Ackr3, Epha3, and St18. Thus, Sp9 has a central transcriptional role in MGE-derived cortical interneuron development.
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  • Vaccination of bovines against Echinococcus granulosus (cystic echinococcosis)

    Robinson, Christine   Shakes, Trevor   Huang, Yan   Gulnur, Tursun   Shi, Baoxing   Zhang, Zhuangzhi   Anderson, Garry A.   Lightowlers, Marshall W.  

    Hydatid disease is an important human zoonosis. Humans become infected from carnivores that are infected with the Echinococcus granulosus tapeworm. Carnivores become infected after consuming hydatid cysts from grazing animals, which are generally sheep, goats and cattle. A vaccine, known as EG95, can protect sheep and goats against cystic echinococcosis. This paper describes the adaptation of the EG95 vaccine for use in cattle. The monitoring of results used serology and also infection with E. granulosus eggs, followed by necropsy. Immunisation with living E. granulosus oncospheres showed that cattle could be immunised against E. granulosus. Immunisation of cattle with EG95 plus QuilA was also successful. A dose-response and adjuvant trial showed best results were achieved with 250 mu g of antigen and 5 mg of the adjuvant QuilA, which was 5 times the recommended sheep dose. After two vaccinations given one month apart, 90% protection was maintained for 12 months. At 12 months a third vaccination boosted protection to 99% which was maintained for a further 11 months. (C) 2012 Elsevier Ltd. All rights reserved.
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  • Determination of genetic diversity among Saccharina germplasm using ISSR and RAPD markers

    Cui, Cuiju   Li, Yan   Liu, Yanling   Li, Xiaojie   Luo, Shiju   Zhang, Zhuangzhi   Wu, Ruina   Liang, Guangjin   Sun, Juan   Peng, Jie   Tian, Pingping  

    Various species of genus Saccharina are economically important brown macroalgae cultivated in China. The genetic background of the conserved Saccharina germplasm was not clear. In this report, DNA-based molecular markers such as inter simple sequence repeats (ISSR) and random amplified polymorphic DNA (RAPD) were used to assess the genetic diversity and phylogenetic relationships among 48 Saccharina germplasms. A total of 50 ISSR and 50 RAPD primers were tested, of which only 33 polymorphic primers (17 ISSR and 16 RAPD) had an amplified clear and reproducible profile, and could be used. Seventeen ISSR primers yielded a total of 262 bands, of which 256 were polymorphic, and 15.06 polymorphic bands per primer were amplified from 48 kelp gametophytes. Sixteen RAPD primers produced 355 bands, of which 352 were polymorphic, and 22 polymorphic bands per primer were observed across 48 individuals. The simple matching coefficient of ISSR, RAPD and pooled ISSR and RAPD dendrograms ranged from 0.568 to 0.885, 0.670 to 0.873, and 0.667 to 0.862, revealing high genetic diversity. Based on the unweighted pair group method with the arithmetic averaging algorithm (UPGMA) cluster analysis and the principal components analysis (PCA) of ISSR data, the 48 gametophytes were divided into three main groups. The Mantel test revealed a similar polymorphism distribution pattern between ISSR and RAPD markers, the correlation coefficient r was 0.62, and the results indicated that both ISSR and RAPD markers were effective to assess the selected gametophytes, while matrix correlation of the ISSR marker system (r =3D 0.78) was better than that of the RAPD marker system (r =3D 0.64). Genetic analysis data from this study were helpful in understanding the genetic relationships among the selected 17 kelp varieties (or lines) and provided guidance for molecular-assisted selection for parental gametophytes of hybrid kelp breeding. (C) 2016 Academie des sciences. Published by Elsevier Masson SAS. All rights reserved.
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  • Transcription Factors Sp8 and Sp9 Coordinately Regulate Olfactory Bulb Interneuron Development

    Li, Jiwen   Wang, Chunyang   Zhang, Zhuangzhi   Wen, Yan   An, Lei   Liang, Qifei   Xu, Zhejun   Wei, Song   Li, Weiwei   Guo, Teng   Liu, Guoping   Tao, Guangxu   You, Yan   Du, Heng   Fu, Zhuoning   He, Miao   Chen, Bin   Campbell, Kenneth   Alvarez-Buylla, Arturo   Rubenstein, John L.   Yang, Zhengang  

    Neural stem cells in the postnatal telencephalic ventricular-subventricular zone (V-SVZ) generate new interneurons, which migrate tangentially through the rostral migratory stream (RMS) into the olfactory bulb (OB). The Sp8 and Sp9 transcription factors are expressed in neuroblasts, as well as in the immature and mature intemeurons in the V-SVZ-RMS-OB system. Here we show that Sp8 and Sp9 coordinately regulate OB interneuron development: although Sp9 null mutants show no major OB interneuron defect, conditional deletion of both Sp8 and Sp9 resulted in a much more severe reduction of OB interneuron number than that observed in the Sp8 conditional mutant mice, due to defects in neuronal differentiation, tangential and radial migration, and increased cell death in the V-SVZ-RMS-OB system. RNA-Seq and RNA in situ hybridization reveal that, in Sp8/Sp9 double mutant mice, but not in Sp8 or Sp9 single mutant mice, newly born neuroblasts in the V-SVZ-RMS-OB system fail to express Prokr2 and Tshz1 expression, genes with known roles in promoting OB interneuron differentiation and migration, and that are involved in human Kallmann syndrome.
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  • A Pilot Study for Control of Hyperendemic Cystic Hydatid Disease in China RID A-8455-2011

    Zhang, Wenbao   Zhang, Zhuangzhi   Yimit, Turhong   Shi, Baoxin   Aili, Hasyeti   Tulson, Gulnor   You, Hong   Li, Jun   Gray, Darren J.   McManus, Donald P.   Wang, Jincheng  

    Background: Cystic hydatid disease (CHD) is a global parasitic zoonosis caused by the dog tapeworm, Echinococcus granulosus. The disease is hyperendemic in western China because of poor economic development; limited community knowledge of CHD; widespread, small-scale household animal production; home killing of livestock; and the feeding of dogs with uncooked offal. Methodology/Principal Findings: A control program focusing on monthly praziquantel (PZQ) treatment of all registered dogs and culling unwanted and stray dogs has been designed to control CHD in hyperendemic areas in China. A pilot field control project in two counties (Hutubi and Wensu) in Xinjiang, China showed that after 4 years of treatment, the prevalence of dogs with E. granulosus was reduced from 14.7% and 18.6%, respectively, to 0%, and this caused a 90%-100% decrease of CHD in sheep born after commencement of the control program. Conclusions/Significance: The strategy aimed at preventing eggs being released from dogs into the environment by treating animals before adult tapeworms are patent can decrease E. granulosus transmission and considerably reduce hyperendemic CHD. Monthly treatment of dogs with PZQ and culling unwanted and stray dogs have been shown to be an efficient, highly cost-effective and practicable measure for implementation in rural communities. As a result, the Chinese Ministry of Health has launched an extensive CHD control program in 117 counties in western China using this control strategy.
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  • The PROK2/PROKR2 signaling pathway is required for the migration of most olfactory bulb interneurons

    Wen, Yan   Zhang, Zhuangzhi   Li, Zhenmeiyu   Liu, Guoping   Tao, Guangxu   Song, Xiaolei   Xu, Zhejun   Shang, Zicong   Guo, Teng   Su, Zihao   Chen, Haotian   You, Yan   Li, Jiada  

    Neural stem cells in the subventricular zone (SVZ) of the lateral ventricle generate new interneurons, which migrate tangentially through the rostral migratory stream (RMS) to the olfactory bulb (OB). The PROK2 (prokineticin 2) and PROKR2 (prokineticin receptor 2) signaling pathway has been identified to cause human Kallmann syndrome, a developmental disease that associates hypogonadism with anosmia (OB developmental defects). However, the identities and properties of PROK2(+) and PROKR2(+) cells in the SVZ-RMS-OB remain largely unknown. Here we examine the expression patterns of Prok2 and Prokr2 in the SVZ-RMS-OB using Prok2(EGFP) transgenic and Prokr2(LacZ/+) knockin mice. Our results show that Prokr2 is expressed in postmitotic immature interneurons in the SVZ-RMS-OB. Prok2 is not expressed in the SVZ, but a few PROK2(+) cells are found in the medial part of the RMS; they are not neural progenitors or migrating neuroblasts. In the OB, Prok2 is expressed in a subset of granule cells and tufted cells, but no coexpression of Prok2 and Prokr2 in the OB cells is observed. In Prok2 and Prokr2 mutant mice, severe tangential and radial migration defects of neuroblasts in the SVZ-RMS-OB result in loss of similar to 75% of GABAergic interneurons in the OB. These analyses demonstrate that PROK2/PROKR2 signaling is crucial for the tangential and radial migration of OB interneurons.
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  • Solid lipid nanoparticle suspension enhanced the therapeutic efficacy of praziquantel against tapeworm

    Xie, Shuyu   Pan, Baoliang   Shi, Baoxin   Zhang, Zhuangzhi   Zhang, Xu  

    Hydatid disease caused by tapeworm is an increasing public health and socioeconomic concern. In order to enhance the therapeutic efficacy of praziquantel (PZQ) against tapeworm, PZQ-loaded hydrogenated castor oil solid lipid nanoparticle (PZQ-HCO-SLN) suspension was prepared by a hot homogenization and ultrasonication method. The stability of the suspension at 4 C and room temperature was evaluated by the physicochemical characteristics of the nanoparticles and in-vitro release pattern of the suspension. Pharmacokinetics was studied after subcutaneous administration of the suspension in dogs. The therapeutic effect of the novel formulation was evaluated in dogs naturally infected with Echinococcus granulosus. The results showed that the drug recovery of the suspension was 97.59% +/- 7.56%. Nanoparticle diameter, polydispersivity index, and zeta potential were 263.00 +/- 11.15 nm, 0.34 +/- 0.06, and -11.57 +/- 1.12 mV, respectively and showed no significant changes after 4 months of storage at both 4 degrees C and room temperature. The stored suspensions displayed similar in-vitro release patterns as that of the newly prepared one. SLNs increased the bioavailability of PZQ 5.67-fold and extended the mean residence time of the drug from 56.71 to 280.38 hours. Single subcutaneous administration of PZQ-HCO-SLN suspension obtained enhanced therapeutic efficacy against tapeworm in infected dogs. At the dose of 5 mg/kg, the stool-ova reduction and negative conversion rates and tapeworm removal rate of the suspension were 100%, while the native PZQ were 91.55%, 87.5%, and 66.7%. When the dose reduced to 0.5 mg/kg, the native drug showed no effect, but the suspension still got the same therapeutic efficacy as that of the 5 mg/kg native PZQ. These results demonstrate that the PZQ-HCO-SLN suspension is a promising formulation to enhance the therapeutic efficacy of PZQ.
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  • SP8 and SP9 coordinately promote D2-type medium spiny neuron production by activating Six3 expression

    Xu, Zhejun   Liang, Qifei   Song, Xiaolei   Zhang, Zhuangzhi   Lindtner, Susan   Li, Zhenmeiyu   Wen, Yan   Liu, Guoping   Guo, Teng   Qi, Dashi   Wang, Min   Wang, Chunyang   Li, Hao   You, Yan   Wang, Xin   Chen, Bin   Feng, Hua   Rubenstein, John L.   Yang, Zhengang  

    Dopamine receptor DRD1-expressing medium spiny neurons (D1 MSNs) and dopamine receptor DRD2-expressing medium spiny neurons (D2 MSNs) are the principal projection neurons in the striatum, which is divided into dorsal striatum (caudate nucleus and putamen) and ventral striatum (nucleus accumbens and olfactory tubercle). Progenitors of these neurons arise in the lateral ganglionic eminence (LGE). Using conditional deletion, we show that mice lacking the transcription factor genes Sp8 and Sp9 lose virtually all D2 MSNs as a result of reduced neurogenesis in the LGE, whereas D1 MSNs are largely unaffected. SP8 and SP9 together drive expression of the transcription factor Six3 in a spatially restricted domain of the LGE subventricular zone. Conditional deletion of Six3 also prevents the formation of most D2 MSNs, phenocopying the Sp8/9 mutants. Finally, ChIP-Seq reveals that SP9 directly binds to the promoter and a putative enhancer of Six3. Thus, this study defines components of a transcription pathway in a regionally restricted LGE progenitor domain that selectively drives the generation of D2 MSNs.
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  • Cortical Neural Stem Cell Lineage Progression Is Regulated by Extrinsic Signaling Molecule Sonic Hedgehog

    Zhang, Yue   Liu, Guoping   Guo, Teng   Liang, Xiaoyi G.   Du, Heng   Yang, Lin   Bhaduri, Aparna   Li, Xiaosu   Xu, Zhejun   Zhang, Zhuangzhi   Li, Zhenmeiyu   He, Miao   Tsyporin, Jeremiah   Kriegstein, Arnold R.   Rubenstein, John L.   Yang, Zhengang   Chen, Bin  

    Neural stem cells (NSCs) in the prenatal neocortex progressively generate different subtypes of glutamatergic projection neurons. Following that, NSCs have a major switch in their progenitor properties and produce g-aminobutyric acid (GABAergic) interneurons for the olfactory bulb (OB), cortical oligodendrocytes, and astrocytes. Herein, we provide evidence for the molecular mechanism that underlies this switch in the state of neocortical NSCs. We show that, at around E16.5, mouse neocortical NSCs start to generate GSX2-expressing (GSX2(+)) intermediate progenitor cells (IPCs). In vivo lineage-tracing study revealed that GSX2(+) IPC population gives rise not only to OB interneurons but also to cortical oligodendrocytes and astrocytes, suggesting that they are a tri-potential population. We demonstrated that Sonic hedgehog signaling is both necessary and sufficient for the generation of GSX2(+) IPCs by reducing GLI3R protein levels. Using single-cell RNA sequencing, we identify the transcriptional profile of GSX2(+) IPCs and the process of the lineage switch of cortical NSCs.
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  • Cloning and characterization of an Echinococcus granulosus ecdysteroid hormone nuclear receptor HR3-like gene

    Yang, Mei   Li, Jun   Wu, Jun   Wang, Hui   Guo, Baoping   Wu, Chuanchuan   Shou, Xi   Yang, Ning   Zhang, Zhuangzhi   McManus, Donald P.  

    Cystic echinococcosis is an important parasitic zoonosis caused by the dog tapeworm Echinococcus granulosus. Little is known about adult worm development at the molecular level. Transcription analysis showed that the E. granulosus hormone receptor 3-like (EgHR3) gene was expressed in protoscoleces and adult worms, indicating its role in early adult development. In this study, we cloned and characterized EgHR3 showing that its cDNA contains an open reading frame (ORF) of 1890 bp encoding a 629 amino acid protein, which has a DNA-binding domain (DBD) and a ligand-binding domain (LBD). Immunolocalization revealed the protein was localized in the parenchyma of protoscoleces and adult worms. Real-time PCR analysis showed that EgHR3 was expressed significantly more in adults than in other stages of development (p < 0.01) and that its expression was especially high in the early stage of adult worm development induced by bile acids. EgHR3 siRNA silenced 69-78% of the level of transcription in protoscoleces, which resulted in killing 43.6-60.9% of protoscoleces after 10 days of cultivation in vitro. EgHR3 may play an essential role in early adult worm development and in maintaining adult biological processes and may represent a novel drug or vaccine target against echinococcosis.
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  • Dlx1/2 are Central and Essential Components in the Transcriptional Code for Generating Olfactory Bulb Interneurons

    Guo, Teng   Liu, Guoping   Du, Heng   Wen, Yan   Wei, Song   Li, Zhenmeiyu   Tao, Guangxu   Shang, Zicong   Song, Xiaolei   Zhang, Zhuangzhi   Xu, Zhejun   You, Yan   Chen, Bin   Rubenstein, John L.  

    Generation of olfactory bulb (OB) interneurons requires neural stem/progenitor cell specification, proliferation, differentiation, and young interneuron migration and maturation. Here, we show that the homeobox transcription factors Dlx1/2 are central and essential components in the transcriptional code for generating OB interneurons. In Dlx1/2 constitutive null mutants, the differentiation of GSX2(+) and ASCL1(+) neural stem/progenitor cells in the dorsal lateral ganglionic eminence is blocked, resulting in a failure of OB interneuron generation. In Dlx1/2 conditional mutants (hGFAP-Cre; Dlx1/2(F/-) mice), GSX2(+) and ASCL1(+) neural stem/progenitor cells in the postnatal subventricular zone also fail to differentiate into OB interneurons. In contrast, overexpression of Dlx1&2 in embryonic mouse cortex led to ectopic production of OB-like interneurons that expressed Gad1, Sp8, Sp9, Arx, Pbx3, Etv1, Tshz1, and Prokr2. Pax6 mutants generate cortical ectopia with OB-like interneurons, but do not do so in compound Pax6; Dlx1/2 mutants. We propose that DLX1/2 promote OB interneuron development mainly through activating the expression of Sp8/9, which further promote Tshz1 and Prokr2 expression. Based on this study, in combination with earlier ones, we propose a transcriptional network for the process of OB interneuron development.
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  • In vitro culture of Echinococcus multilocularis producing protoscoleces and mouse infection with the cultured vesicles

    Wang, Hui   Li, Jun   Guo, Baoping   Zhao, Li   Zhang, Zhuangzhi   McManus, Donald P.   Wen, Hao   Zhang, Wenbao  

    Background: Alveolar echinococcosis (AE) is a lethal zoonosis caused by the fox-tapeworm Echinococcus multilocularis. The disease is difficult to treat and an effective therapeutic drug is urgently needed. Reliable models are essential for drug development. In this study, we developed both in vitro and in vivo models of larval E. multilocularis. Results: The protoscoleces (PSC) of E. multilocularis from jirds were successfully cultured in a modified RPMI1640 based medium containing 25 % (v/v) fetal bovine serum (FBS). After 100 days of culture, PSC developed to larval vesicles (small unilocular cysts) and the fast growing vesicles produced PSC in brood capsules. In addition, mice were intraperitoneally injected with 30 cultured small vesicles and 100 % of the mice had resulting metacestode masses. Conclusions: Larval protoscoleces and vesicles of E. multilocularis grow healthily in vitro in the RPMI1640 based medium containing 25 % FBS. Echinococcus multilocularis in vitro and in vivo models provide a valuable platform for investigating the biology of the parasite and screening effective therapeutic drugs against AE.
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  • An in vitro larval migration assay for assessing anthelmintic activity of different drug classes against Ascaris suum

    Zhao, Jianguo   Williams, Andrew R.   Hansen, Tina Vicky Alstrup   Thamsborg, Stig M.   Cai, Jianping   Song, Shuaibao   Chen, Gang   Kang, Ming   Zhang, Zhuangzhi   Liu, Qun  

    In vitro methods have been developed for the detection of anthelmintic resistance in a range of nematode species. However, the life cycle of Ascaris suum renders the commonly used egg hatch assay and larval development assay unusable. In this study we developed a combined multi-well culture and agar gel larval migration assay to test the effect of benzimidazole and tetrahydropyrimidinfimidazothiazole anthelmintics against nine isolates of A. suum collected from locations in China and Denmark. Drugs tested were thiabendazole, fenbendazole, mebendazole, levamisole, and pyrantel. The percentages of larvae that migrated to the surface of each treated and control well were used to calculate the drug concentration which inhibits 50% of the larvae migration (EC50). The values of EC50 of thiabendazole, fenbendazole, mebendazole, levamisole, and pyrantel against A. suum isolates ranged 74-150, 4.9-13.9, 2.3-4.3, 358-1150 and 1100-4000 nM, respectively. This combined multi-well culture and agar gel larval migration assay was a sensitive bioassay for anthelmintic activity and could serve as an in vitro method to detect for lowered drug efficacy against A. suum or possibly to screen for anthelmintic drug candidates. (C) 2017 Elsevier B.V. All rights reserved.
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  • Dendritic cells treated by Trichinella spiralis muscle larval excretory/secretory products alleviate TNBS-induced colitis in mice

    Jin, Xuemin   Yang, Yong   Bai, Xue   Shi, Haining   Zhang, Wenbao   Zhang, Zhuangzhi   Jia, Wanzhong   Lin, Jiaojiao   Liu, Mingyuan   Liu, Xiaolei  

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  • Genome-wide sequencing of small RNAs reveals a tissue-specific loss of conserved microRNA families in Echinococcus granulosus.

    Bai, Yun   Zhang, Zhuangzhi   Jin, Lei   Kang, Hui   Zhu, Yongqiang   Zhang, Lu   Li, Xia   Ma, Fengshou   Zhao, Li   Shi, Baoxin   Li, Jun   McManus, Donald P   Zhang, Wenbao   Wang, Shengyue  

    BACKGROUND: MicroRNAs (miRNAs) are important post-transcriptional regulators which control growth and development in eukaryotes. The cestode Echinococcus granulosus has a complex life-cycle involving different development stages but the mechanisms underpinning this development, including the involvement of miRNAs, remain unknown.; RESULTS: Using Illumina next generation sequencing technology, we sequenced at the genome-wide level three small RNA populations from the adult, protoscolex and cyst membrane of E. granulosus. A total of 94 pre-miRNA candidates (coding 91 mature miRNAs and 39 miRNA stars) were in silico predicted. Through comparison of expression profiles, we found 42 mature miRNAs and 23 miRNA stars expressed with different patterns in the three life stages examined. Furthermore, considering both the previously reported and newly predicted miRNAs, 25 conserved miRNAs families were identified in the E. granulosus genome. Comparing the presence or absence of these miRNA families with the free-living Schmidtea mediterranea, we found 13 conserved miRNAs are lost in E. granulosus, most of which are tissue-specific and involved in the development of ciliated cells, the gut and sensory organs. Finally, GO enrichment analysis of the differentially expressed miRNAs and their potential targets indicated that they may be involved in bi-directional development, nutrient metabolism and nervous system development in E. granulosus.; CONCLUSIONS: This study has, for the first time, provided a comprehensive description of the different expression patterns of miRNAs in three distinct life cycle stages of E. granulosus. The analysis supports earlier suggestions that the loss of miRNAs in the Platyhelminths might be related to morphological simplification. These results may help in the exploration of the mechanism of interaction between this parasitic worm and its definitive and intermediate hosts, providing information that can be used to develop new interventions and therapeutics for the control of cystic echinococcosis.=20
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  • Dendritic cells treated by Trichinella spiralis muscle larval excretory/secretory products alleviate TNBS-induced colitis in mice.

    Jin, Xuemin   Yang, Yong   Bai, Xue   Shi, Haining   Zhang, Wenbao   Zhang, Zhuangzhi   Jia, Wanzhong   Lin, Jiaojiao   Liu, Mingyuan   Liu, Xiaolei  

    BACKGROUND: Therapeutic potential of helminth have been shown to have a protective effect on immune-mediated diseases such as Crohn's disease (CD), which is associated with increased production of T helper cell type 1. However, helminth therapy is unacceptable to patients due to side-effects and the fear of parasites. As helminths regulate the cellular immune responses through innate cells such as dendritic cells (DCs), cellular immunotherapy has been considered a therapeutic option to treat CD.; METHODS: Bone marrow-dendritic cells were generated, enriched and treated with Trichinella spiralis muscle larval excretory/secretory products (Ts-MLES). DCs maturation was measured by flow cytometry and cytokine production of DCs were measured by ELISA. Colitis was generated by intrarectal administration of 2,4,6-trinitrobenzene sulfonic acid (TNBS) solution. For adoptive transfer, Ts-MLES treated-DCs injected intravenously 24=E2=80=AFh prior to TNBS challenge. Disease activity index (DAI) including weight loss, diarrhea, and bloody stool were measured. Colon segments were stained with hematoxylin and eosin (H.E.) and periodic acid schiff (PAS) staining for histological damage scoring. The relative mRNA expression of cytokines in colon was analyzed by RT-PCR. Cytokine production in colon was measured by ELISA. Splenocytes were separated and cytokine profiles including Th1 (IFN-gamma), Th2 (IL-4, IL-13), and Treg subsets (IL-10, TGF-beta) were analyzed by flow cytometry.; RESULTS: Ts-MLES regulated the maturation and cytokine production of DCs. Ts-MLES -DC ameliorated the severity of the TNBS-induced colitis. In the colon and the spleen, Ts-MLES-DC decreased IFN-gamma (Th1) significantly and increased Th2 (IL-4, IL-13)- and Treg (IL-10, TGF-beta)- related cytokines.; CONCLUSIONS: Ts-MLES-DC ameliorated the severity of the TNBS-induced colitis through decreasing IFN-gamma. Ts-MLES-DC skewed the Th1-mediated response toward the Th2 type and regulatory T cell response. Copyright =C2=A9 2019 Elsevier B.V. All rights reserved.
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