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1.
Biochem Soc Trans ; 47(6): 1635-1650, 2019 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-31829403

RESUMO

Taking advantage of high contrast and molecular specificity, fluorescence microscopy has played a critical role in the visualization of subcellular structures and function, enabling unprecedented exploration from cell biology to neuroscience in living animals. To record and quantitatively analyse complex and dynamic biological processes in real time, fluorescence microscopes must be capable of rapid, targeted access deep within samples at high spatial resolutions, using techniques including super-resolution fluorescence microscopy, light sheet fluorescence microscopy, and multiple photon microscopy. In recent years, tremendous breakthroughs have improved the performance of these fluorescence microscopies in spatial resolution, imaging speed, and penetration. Here, we will review recent advancements of these microscopies in terms of the trade-off among spatial resolution, sampling speed and penetration depth and provide a view of their possible applications.


Assuntos
Células/ultraestrutura , Microscopia de Fluorescência/métodos , Animais , Luz , Fótons
2.
ACS Nano ; 13(11): 13382-13389, 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31603304

RESUMO

Oxidative stress is one of the important mechanisms in cerebral ischemia/reperfusion (I/R) injury. Antioxidants with high brain accumulation are highly desired to help prevent cerebral I/R injury. Herein, intrathecal injection of polyoxometalate (POM) nanoclusters as nano-antioxidants with preferential brain uptake were applied for neuronal protection in cerebral I/R injury. Using powerful positron emission tomography imaging, the uptake of nano-antioxidants in the brain was non-invasively and real-timely monitored. Our results demonstrated that POM nanoclusters rapidly reached the ischemic penumbra after intrathecal injection and effectively scavenged reactive oxygen species (ROS) for inhibiting oxidative stress. The infarct size was reduced, and neurological function was restored in cerebral I/R injury rat models. As a proof-of-concept, the intrathecal injection of nano-antioxidants is an excellent therapeutic strategy to ameliorate cerebral I/R injury.

3.
Virol Sin ; 34(6): 610-617, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31359346

RESUMO

Foot-and-mouth disease virus (FMDV) can infect domestic and wild cloven-hoofed animals. The non-structural protein 3D plays an important role in FMDV replication and pathogenesis. However, the interaction partners of 3D, and the effects of those interactions on FMDV replication, remain incompletely elucidated. In the present study, using the yeast two-hybrid system, we identified a porcine cell protein, DEAD-box RNA helicase 1 (DDX1), which interacted with FMDV 3D. The DDX1-3D interaction was further confirmed by co-immunoprecipitation experiments and an indirect immunofluorescence assay (IFA) in porcine kidney 15 (PK-15) cells. DDX1 was reported to either inhibit or facilitate viral replication and regulate host innate immune responses. However, the roles of DDX1 during FMDV infection remain unclear. Our results revealed that DDX1 inhibited FMDV replication in an ATPase/helicase activity-dependent manner. In addition, DDX1 stimulated IFN-ß activation in FMDV-infected cells. Together, our results expand the body of knowledge regarding the role of DDX1 in FMDV infection.

4.
J Virol ; 93(11)2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-30894473

RESUMO

The role of nucleotide-binding oligomerization domain 2 (NOD2) in foot-and-mouth disease virus (FMDV)-infected cells remains unknown. Here, we showed that FMDV infection activated NOD2-mediated beta interferon (IFN-ß) and nuclear factor-κB (NF-ĸB) signaling pathways. NOD2 inhibited FMDV replication in the infected cells. FMDV infection triggered NOD2 transcription, while it reduced the abundance of NOD2 protein. Our results revealed that FMDV 2B, 2C, and 3C proteinase (3Cpro) were responsible for the decrease in NOD2 protein levels. 3Cpro is a viral proteinase that can cleave multiple host proteins and limit protein synthesis. Our previous studies determined that FMDV 2B suppressed protein expression of RIG-I and LGP2. Here, we found that 3Cpro and 2B also decreased NOD2 expression. However, this is the first report that 2C induced the reduction of NOD2 protein levels. We determined that both 2B- and 2C-induced decreases in NOD2 were independent of the cleavage of host eukaryotic translation initiation factor 4 gamma (eIF4G), induction of cellular apoptosis, or proteasome, lysosome, and caspase pathways. The interactions between NOD2 and 2B or 2C were observed in the context of viral infection. The carboxyl-terminal amino acids 105 to 114 and 135 to 144 of 2B were essential for the reduction of NOD2, while the residues 105 to 114 were required for the interaction. Amino acids 116 to 260 of the carboxyl terminus of 2C were essential for the interaction, while truncated 2C mutants did not reduce NOD2. These data suggested novel antagonistic mechanisms of FMDV that were mediated by 2B, 2C, and 3Cpro proteins.IMPORTANCE NOD2 was identified as a cytoplasmic viral pattern recognition receptor in 2009. Subsequently, many viruses were reported to activate NOD2-mediated signaling pathways. This study demonstrated that FMDV infection activated NOD2-mediated IFN-ß and NF-ĸB signaling pathways. Host cells have developed multiple strategies against viral infection; however, viruses have evolved many strategies to escape host defenses. FMDV has evolved multiple mechanisms to inhibit host type I IFN production. Here, we showed that NOD2 suppressed FMDV replication during viral infection. FMDV 2B, 2C, and 3Cpro decreased NOD2 protein expression by different mechanisms to promote viral replication. This study provided new insight into the immune evasion mechanisms mediated by FMDV and identified 2B, 2C, and 3Cpro as antagonistic factors for FMDV to evade host antiviral responses.

5.
Antiviral Res ; 160: 183-189, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30408499

RESUMO

The mechanisms that enable Seneca Valley Virus (SVV) to escape the host innate immune response are not well known. Previous studies demonstrated that SVV 3Cpro suppresses innate immune responses by cleavage of host proteins and degradation of IRF3 and IRF7 protein expression. Here, we showed that SVV 3C protease (3Cpro) has deubiquitinating activity. Overexpressed 3Cpro inhibits the ubiquitination of cellular substrates, acting on both lysine-48- and lysine-63-linked polyubiquitin chains. SVV infection also possessed deubiquitinating activity. The ubiquitin-proteasome system was significantly involved in SVV replication. Furthermore, 3Cpro inhibited the ubiquitination of retinoic acid-inducible gene I (RIG-I), TANK-binding kinase 1 (TBK1), and TNF receptor-associated factor 3 (TRAF3), thereby blocking the expression of interferon (IFN)-ß and IFN stimulated gene 54 (ISG54) mRNAs. A detailed analysis revealed that mutations (H48A, C160A, or H48A/C160A) that ablate the Cys and His residues of 3Cpro abrogated its deubiquitinating activity and the ability of 3Cpro to block IFN-ß induction. Together, our results demonstrate a novel mechanism developed by SVV 3Cpro to promote viral replication, and may also provide a novel strategy for improving ubiquitination-based therapy.


Assuntos
Cisteína Endopeptidases/metabolismo , Enzimas Desubiquitinantes/metabolismo , Interações Hospedeiro-Patógeno , Evasão da Resposta Imune , Picornaviridae/imunologia , Picornaviridae/patogenicidade , Proteínas Virais/metabolismo , Substituição de Aminoácidos , Análise Mutacional de DNA , Fatores Imunológicos/metabolismo , Picornaviridae/crescimento & desenvolvimento , Replicação Viral
6.
J Am Chem Soc ; 140(44): 14971-14979, 2018 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-30336003

RESUMO

The interaction between radionuclides and nanomaterials could generate Cerenkov radiation (CR) for CR-induced photodynamic therapy (PDT) without requirement of external light excitation. However, the relatively weak CR interaction leaves clinicians uncertain about the benefits of this new type of PDT. Therefore, a novel strategy to amplify the therapeutic effect of CR-induced PDT is imminently required to overcome the disadvantages of traditional nanoparticulate PDT such as tissue penetration limitation, external light dependence, and low tumor accumulation of photosensitizers. Herein, magnetic nanoparticles (MNPs) with 89Zr radiolabeling and porphyrin molecules (TCPP) surface modification (i.e., 89Zr-MNP/TCPP) were synthesized for CR-induced PDT with magnetic targeting tumor delivery. As a novel strategy to break the depth and light dependence of traditional PDT, these 89Zr-MNP/TCPP exhibited high tumor accumulation under the presence of an external magnetic field, contributing to excellent tumor photodynamic therapeutic effect together with fluorescence, Cerenkov luminescence (CL), and Cerenkov resonance energy transfer (CRET) multimodal imaging to monitor the therapeutic process. The present study provides a major step forward in photodynamic therapy by developing an advanced phototherapy tool of magnetism-enhanced CR-induced PDT for effective targeting and treatment of tumors.


Assuntos
Nanopartículas de Magnetita/química , Fotoquimioterapia , Animais , Sobrevivência Celular/efeitos dos fármacos , Feminino , Transferência Ressonante de Energia de Fluorescência , Humanos , Neoplasias Mamárias Experimentais/diagnóstico por imagem , Neoplasias Mamárias Experimentais/patologia , Camundongos , Camundongos Endogâmicos BALB C , Porfirinas/química , Porfirinas/farmacologia , Tomografia por Emissão de Pósitrons , Radioisótopos/química , Radioisótopos/farmacologia , Células Tumorais Cultivadas , Zircônio/química , Zircônio/farmacologia
7.
FASEB J ; : fj201701351, 2018 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-29906248

RESUMO

Foot-and-mouth disease (FMD) is a highly contagious virus that affects cloven-hoofed animals. To understand better the role of nonstructural protein 2B of the causative agent FMD virus (FMDV) in the process of virus replication, we identified a porcine host protein, cyclophilin A (CypA), which interacts with FMDV 2B. The 2B-CypA interaction was confirmed by coimmunoprecipitation and GST pull-down assays. CypA showed antiviral functions during FMDV infection. Overexpression of CypA decreased FMDV leader protein (Lpro) and 3A at protein levels. CypA-induced reduction of Lpro enhanced the synthesis of host proteins and increased the integrality of host eukaryotic translation initiation factor (eIF)-4γ (eIF4G). The reduction of Lpro and 3A was dependent on the proteasome pathway. No interaction was identified between CypA and Lpro or 3A. However, CypA-induced reduction of Lpro and 3A was suppressed by 2B, and disruption of 2B-CypA interaction impaired this inhibitive effect induced by 2B. In summary, our findings identify the antiviral role of CypA against FMDV and provide key insights into how FMDV antagonizes host antiviral response by 2B protein.-Liu, H., Xue, Q., Cao, W., Yang, F., Ma, L., Liu, W., Zhang, K., Liu, X., Zhu, Z., Zheng, H. Foot-and-mouth disease virus nonstructural protein 2B interacts with cyclophilin A, modulating virus replication.

8.
Cell ; 173(4): 934-945.e12, 2018 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-29606354

RESUMO

Fusion is thought to open a pore to release vesicular cargoes vital for many biological processes, including exocytosis, intracellular trafficking, fertilization, and viral entry. However, fusion pores have not been observed and thus proved in live cells. Its regulatory mechanisms and functions remain poorly understood. With super-resolution STED microscopy, we observed dynamic fusion pore behaviors in live (neuroendocrine) cells, including opening, expansion, constriction, and closure, where pore size may vary between 0 and 490 nm within 26 milliseconds to seconds (vesicle size: 180-720 nm). These pore dynamics crucially determine the efficiency of vesicular cargo release and vesicle retrieval. They are generated by competition between pore expansion and constriction. Pharmacology and mutation experiments suggest that expansion and constriction are mediated by F-actin-dependent membrane tension and calcium/dynamin, respectively. These findings provide the missing live-cell evidence, proving the fusion-pore hypothesis, and establish a live-cell dynamic-pore theory accounting for fusion, fission, and their regulation.


Assuntos
Membrana Celular/metabolismo , Endocitose/fisiologia , Fusão de Membrana/fisiologia , Actinas/metabolismo , Animais , Cálcio/metabolismo , Bovinos , Membrana Celular/química , Células Cromafins/citologia , Células Cromafins/metabolismo , Dinaminas/metabolismo , Estimulação Elétrica , Corantes Fluorescentes/química , Corantes Fluorescentes/metabolismo , Masculino , Microscopia Confocal , Modelos Biológicos , Técnicas de Patch-Clamp , Vesículas Secretórias/fisiologia
9.
Virology ; 518: 1-7, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29427864

RESUMO

Seneca Valley Virus (SVV) is a newly emerged virus belonging to the family Picornaviridae. Basic knowledge of the immunological response to SVV is limited. To date, one study has demonstrated that SVV 3Cpro mediates the cleavage of host MAVS, TRIF, and TANK at specific sites and consequently escapes the host's antiviral innate immunity. In this study, we show that SVV 3Cpro reduces IRF3 and IRF7 protein expression level and phosphorylation. SVV infection also reduces expression of IRF3 and IRF7 protein. The degradation of IRF3 and IRF7 is dependent on the 3Cpro protease activity. We also identify interactions between 3Cpro and IRF3 and IRF7 in PK-15 cells. A detailed analysis revealed that the degradation of IRF3 and IRF7 blocks the transcription of IFN-ß, IFN-α1, IFN-α4, and ISG54. Together, our results demonstrate a novel mechanism developed by SVV 3Cpro to allow the virus to escape the host's intrinsic innate immune system.


Assuntos
Regulação da Expressão Gênica/imunologia , Imunidade Inata , Fator Regulador 3 de Interferon/metabolismo , Fator Regulador 7 de Interferon/metabolismo , Picornaviridae/classificação , Picornaviridae/fisiologia , Animais , Linhagem Celular , Humanos , Fator Regulador 3 de Interferon/genética , Fator Regulador 7 de Interferon/genética , Suínos
10.
J Vet Diagn Invest ; 30(2): 245-248, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29105585

RESUMO

Citrobacter freundii is considered a ubiquitous organism and an opportunistic pathogen. Reports of C. freundii-associated disease in mammals have been very limited. We report an outbreak of C. freundii septicemia and encephalitis in sheep, with a high mortality rate; 13 adult sheep were found dead over a 6-d period on a farm in central China that housed ~1,370 sheep. Three animals were autopsied and showed septicemia, congestion of meningeal vessels, and pleural effusion. C. freundii was isolated in abundance in pure culture from 19 of 21 organs. All 3 C. freundii isolates had similar antimicrobial resistance phenotypes for 10 of the 11 agents tested, and were sensitive to 8 of the 11 agents. We reproduced C. freundii infection in sheep experimentally by oral or subcutaneous inoculation routes, and recovered the challenge organism from all of the experimentally infected sheep. Intramuscular injection of enrofloxacin protected sheep against an otherwise fatal challenge. Our results suggest that C. freundii played a major role in this disease outbreak.


Assuntos
Citrobacter freundii/isolamento & purificação , Surtos de Doenças/veterinária , Encefalite/veterinária , Infecções por Enterobacteriaceae/veterinária , Sepse/veterinária , Doenças dos Ovinos/mortalidade , Animais , China/epidemiologia , Encefalite/epidemiologia , Encefalite/mortalidade , Infecções por Enterobacteriaceae/epidemiologia , Infecções por Enterobacteriaceae/mortalidade , Feminino , Testes de Sensibilidade Microbiana/veterinária , Sepse/epidemiologia , Sepse/mortalidade , Ovinos , Doenças dos Ovinos/epidemiologia , Doenças dos Ovinos/microbiologia
11.
Biomed Res Int ; 2017: 2481348, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29226127

RESUMO

Foot-and-mouth disease virus (FMDV) is the etiological agent of FMD, which affects domestic and wild cloven-hoofed animals. The structural protein VP1 plays an important role in FMDV pathogenesis. However, the interacting partners of VP1 in host cells and the effects of these interactions in FMDV replication remain incompletely elucidated. Here, we identified a porcine cell protein, serine/threonine kinase 3 (STK3), which interacts with FMDV VP1 using the yeast two-hybrid system. The VP1-STK3 interaction was further confirmed by coimmunoprecipitation experiments in human embryonic kidney 293T and porcine kidney 15 (PK-15) cells. The carboxyl-terminal region (amino acids 180-214) of VP1 was essential for its interaction with STK3. The effects of overexpression and underexpressing of STK3 in PK-15 cells were assessed, and the results indicated that STK3 significantly inhibited FMDV replication. Our data expand the role of STK3 during viral infection, provide new information regarding the host cell kinases that are involved in viral replication, and identify potential targets for future antiviral strategies.


Assuntos
Proteínas do Capsídeo/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Virais/metabolismo , Replicação Viral/fisiologia , Animais , Antivirais/farmacologia , Linhagem Celular , Febre Aftosa/tratamento farmacológico , Febre Aftosa/virologia , Vírus da Febre Aftosa/efeitos dos fármacos , Células HEK293 , Humanos , Suínos , Replicação Viral/efeitos dos fármacos
12.
Biophys J ; 113(11): 2406-2414, 2017 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-29211994

RESUMO

Endocytosis generates spherical or ellipsoid-like vesicles from the plasma membrane, which recycles vesicles that fuse with the plasma member during exocytosis in neurons and endocrine secretory cells. Although tension in the plasma membrane is generally considered to be an important factor in regulating endocytosis, whether membrane tension inhibits or facilitates endocytosis remains debated in the endocytosis field, and has been rarely studied for vesicular endocytosis in secretory cells. Here we report that increasing membrane tension by adjusting osmolarity inhibited both the rapid (a few seconds) and slow (tens of seconds) endocytosis in calyx-type nerve terminals containing conventional active zones and in neuroendocrine chromaffin cells. We address the mechanism of this phenomenon by computational modeling of the energy barrier that the system must overcome at the stage of membrane budding by an assembling protein coat. We show that this barrier grows with increasing tension, which may slow down or prevent membrane budding. These results suggest that in live secretory cells, membrane tension exerts inhibitory action on endocytosis.


Assuntos
Membrana Celular/metabolismo , Células Cromafins/citologia , Células Cromafins/metabolismo , Endocitose , Animais , Feminino , Espaço Intracelular/metabolismo , Cinética , Masculino , Camundongos , Concentração Osmolar
13.
Vet Immunol Immunopathol ; 186: 51-54, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28413050

RESUMO

This study evaluated whether there was an association between polymorphisms within the Toll-like receptor 2 gene (TLR2) of Chinese Holstein cattle and susceptibility to bovine tuberculosis (BTB). In a case-control study including 210 BTB cases and 237 control cattle, we found only two common single-nucleotide polymorphisms (SNPs) within the entire coding region of the TLR2 gene, A631G (rs95214857) and T1707C (rs1388116488). Additionally, the allele and genotype distributions of A631G and T1707C were not different between case and control groups, indicated that these SNPs were not associated with susceptibility to BTB. These results suggested that polymorphisms in the TLR2 gene might not play a significant role in the BTB risk in Chinese Holstein cattle.


Assuntos
Polimorfismo de Nucleotídeo Único , Receptor 2 Toll-Like/genética , Tuberculose Bovina/genética , Animais , Bovinos , China
14.
Can J Vet Res ; 81(1): 22-27, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28154458

RESUMO

The objective of this study was to assess the efficacy of a trivalent inactivated Haemophilus parasuis serovars 4, 5, and 12 vaccine with polymeric adjuvant gel (GEL) and commercial vaccines against Glässer's disease in piglets. Commercial vaccines containing inactivated H. parasuis serovars 4 and 5 (China), inactivated H. parasuis serovars 1 and 6 (Spain), and inactivated H. parasuis serovar 5 (USA) were also evaluated. Our results demonstrated that the trivalent inactivated H. parasuis serovars 4, 5, and 12 vaccine with GEL adjuvant can provide better protection against the 3 most common pathogenic serovars circulating in China than other commercial vaccines tested. Our findings also indicated that inactivated H. parasuis serovars 1 and 6 vaccine cross-protects piglets against H. parasuis serovars 4 and 5; inactivated H. parasuis serovar 5 vaccine cross-protects piglets against H. parasuis serovar 4 challenge; but none of the commercial vaccines tested in this study protected piglets against H. parasuis serovar 12. Our results provide a basis for further identification of common protective antigens that can induce cross-protection against heterogeneous serovars.


Assuntos
Vacinas Bacterianas/imunologia , Infecções por Haemophilus/veterinária , Haemophilus parasuis/classificação , Doenças dos Suínos/prevenção & controle , Animais , Anticorpos Antibacterianos/sangue , Vacinas Bacterianas/efeitos adversos , Feminino , Infecções por Haemophilus/microbiologia , Infecções por Haemophilus/prevenção & controle , Sorogrupo , Suínos , Vacinas de Produtos Inativados/efeitos adversos , Vacinas de Produtos Inativados/imunologia
15.
Ir Vet J ; 70: 2, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28078081

RESUMO

BACKGROUND: Prior to the 1990s, P. multocida capsular serogroup A was the most prevalent in China, followed by serogroups B and D. Thirty years later, serogroup D became the most prevalent, followed by serogroups A and B. However, the P. multocida capsular serogroups currently circulating in China remain unclear. Therefore, the aim of the present study was to provide an update on P. multocida serogroups isolated from diagnostic samples collected from clinically diseased pigs in Central and Eastern China from 2011 to 2015. RESULTS: Between February 2011 and October 2015, 296 isolates of Pasteurella multocida were collected from 3212 pigs with clinical respiratory disease in 12 provinces of China (isolation rate of 9.2%). Of the 296 collected isolates, 146 (49.3%) were P. multocida capsular type A, 141 (47.6%) were capsular type D, and one was capsular type B. Streptococcus suis (94/193; 48.7%), Haemophilus parasuis (76/193; 39.3%), Escherichia coli (53/193; 27.5%), and Bordetella bronchiseptica (26/193; 13.5%) were frequently isolated together with P. multocida. A total of 14 toxigenic P. multocida strains co-isolated with other pathogens from 32 cases of atrophic rhinitis were classified into serogroup D. The virulence of P. multocida capsular type A isolates was higher than that of capsular type D isolates based on LD50 studies in mice. CONCLUSIONS: Over the past 5 years, P. multocida capsular type A was the most frequently isolated from diagnostic submissions in Central and Eastern China, followed by serogroups D and B.

16.
Can J Vet Res ; 80(4): 287-293, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27733783

RESUMO

The objective of this study was to assess the minimum dose, antigen content, and immunization duration of a trivalent vaccine containing inactivated Haemophilus parasuis serovars 4, 5, and 12 and the Montanide GEL 01 PR adjuvant in piglets and pregnant sows. Our results demonstrated that the minimum vaccine dose was 2 mL per pig and the optimal antigen content 2.0 × 109, 1.0 × 109, and 1.0 × 109 colony-forming units/mL of serovars 4, 5, and 12, respectively. The vaccine provided effective protection 14 d after the 2nd vaccination, and the period of immune protection was 180 d (6 mo) after the 2nd vaccination. Maternal antibodies provided early protection for the piglets, and vaccinating the sows before farrowing helped to control disease and protected the piglets during lactation; the piglets were protected during the finishing period by being vaccinated during lactation. Our findings provide a basis for developing a commercial trivalent vaccine of inactivated H. parasuis serovars 4, 5, and 12 against Glässer's disease.


Assuntos
Antígenos de Bactérias/química , Vacinas Bacterianas/imunologia , Infecções por Haemophilus/veterinária , Haemophilus parasuis , Animais , Antígenos de Bactérias/imunologia , Relação Dose-Resposta Imunológica , Feminino , Infecções por Haemophilus/microbiologia , Infecções por Haemophilus/prevenção & controle , Imunização , Gravidez , Suínos , Vacinas de Produtos Inativados/imunologia
17.
Vet Immunol Immunopathol ; 180: 53-58, 2016 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-27692096

RESUMO

Glässer's disease, which is caused by Haemophilus parasuis, is a major threat to swine throughout the world. At present, the predominant method of controlling this disease is through vaccination with an inactivated vaccine, which has many limitations. For example, there is no available method to differentiate between infected and vaccinated animals. In addition, inactivated vaccines do not contain all of the virulent serovars that circulate in a region. Additionally, novel vaccines that address the shortcomings of inactivated vaccines are not available. Here, we summarize existing knowledge concerning H. parasuis vaccines, and provide some suggestions that may help to improve H. parasuis vaccines.


Assuntos
Vacinas Anti-Haemophilus/imunologia , Haemophilus parasuis/imunologia , Animais , Engenharia Genética , Suínos , Vacinas de DNA/imunologia , Vacinas de Produtos Inativados/imunologia , Vacinas de Subunidades/imunologia
18.
BMC Vet Res ; 12(1): 138, 2016 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-27377264

RESUMO

BACKGROUND: There is no information concerning the genotype of Canine parvovirus (CPV) currently circulating in Henan province, China. Therefore, the aim of the present study was to provide insights into the epidemiology and molecular characterization of CPV circulating in Henan province from 2009 to 2014. RESULTS: Nineteen thousand nine hundred seven dogs from pet hospitals in the cities of Luoyang, Anyang, Jiaozuo, Sanmenxia, Xinxiang, Zhengzhou in Henan province between 2009 and 2014 were investigated. Over the 6-year period, 1169 CPV-positive cases were identified and the morbidity of CPV infection ranged from 4.16 to 8.06 %, although morbidity was not significant (P > 0.05) between 2009 and 2014. Factors associated with morbidity included sampling season, dog age, breed, vaccination status, and sex. CPV co-infection with coccidium (10.00 %), canine distemper virus (4.79 %), hookworm (2.40 %), canine coronavirus (1.11 %), roundworm (1.03 %), tapeworm (0.17 %) and Babesia spp. (0.09 %) were observed. The new CPV-2a variant was more prevalent than the new CPV-2b variant in Henan province. CPV 2c was not observed in this study. CONCLUSIONS: The epidemiology of CPV infection and identification of the circulating genotypes in Henan province, China from 2009 to 2014 determined that the new CPV-2a variant was more prevalent.


Assuntos
Doenças do Cão/epidemiologia , Infecções por Parvoviridae/veterinária , Animais , Proteínas do Capsídeo/genética , China/epidemiologia , Coinfecção , Cães , Feminino , Genótipo , Masculino , Tipagem Molecular , Infecções por Parvoviridae/epidemiologia , Parvovirus Canino/genética , Prevalência , Fatores de Risco
19.
Cell Stem Cell ; 18(6): 817-26, 2016 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-27133795

RESUMO

Transplantation of human pluripotent stem cell (hPSC)-derived neurons is a promising avenue for treating disorders including Parkinson's disease (PD). Precise control over engrafted cell activity is highly desired, as cells do not always integrate properly into host circuitry and can cause suboptimal graft function or undesired outcomes. Here, we show tunable rescue of motor function in a mouse model of PD, following transplantation of human midbrain dopaminergic (mDA) neurons differentiated from hPSCs engineered to express DREADDs (designer receptors exclusively activated by designer drug). Administering clozapine-N-oxide (CNO) enabled precise DREADD-dependent stimulation or inhibition of engrafted neurons, revealing D1 receptor-dependent regulation of host neuronal circuitry by engrafted cells. Transplanted cells rescued motor defects, which could be reversed or enhanced by CNO-based control of graft function, and activating engrafted cells drives behavioral changes in transplanted mice. These results highlight the ability to exogenously and noninvasively control and refine therapeutic outcomes following cell transplantation.


Assuntos
Neurônios/transplante , Doença de Parkinson/terapia , Células-Tronco Pluripotentes/citologia , Transplante de Células-Tronco , Animais , Diferenciação Celular , Linhagem Celular , Clozapina/análogos & derivados , Modelos Animais de Doenças , Neurônios Dopaminérgicos/metabolismo , Desenho de Drogas , Potenciais Pós-Sinápticos Excitadores , Glutamatos/metabolismo , Células-Tronco Embrionárias Humanas/metabolismo , Humanos , Mesencéfalo/patologia , Camundongos , Atividade Motora , Neostriado/metabolismo , Doença de Parkinson/patologia , Doença de Parkinson/fisiopatologia , Receptores de Dopamina D1/metabolismo , Ácido gama-Aminobutírico/metabolismo
20.
Nat Biotechnol ; 34(1): 89-94, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26655496

RESUMO

Serotonin neurons located in the raphe nucleus of the hindbrain have crucial roles in regulating brain functions and have been implicated in various psychiatric disorders. Yet functional human serotonin neurons are not available for in vitro studies. Through manipulation of the WNT pathway, we demonstrate efficient differentiation of human pluripotent stem cells (hPSCs) to cells resembling central serotonin neurons, primarily those located in the rhombomeric segments 2-3 of the rostral raphe, which participate in high-order brain functions. The serotonin neurons express a series of molecules essential for serotonergic development, including tryptophan hydroxylase 2, exhibit typical electrophysiological properties and release serotonin in an activity-dependent manner. When treated with the FDA-approved drugs tramadol and escitalopram oxalate, they release or uptake serotonin in a dose- and time-dependent manner, suggesting the utility of these cells for the evaluation of drug candidates.


Assuntos
Neurônios/citologia , Células-Tronco Pluripotentes/citologia , Serotonina/metabolismo , Humanos , Neurônios/metabolismo
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