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1.
J Org Chem ; 86(23): 17063-17070, 2021 12 03.
Artigo em Inglês | MEDLINE | ID: mdl-34797073

RESUMO

A tandem rhodium(III)-catalyzed system was established to access 3,4-dihydroisoquinolin-1(2H)-one by coupling of N-methoxy-3-methylbenzamide with 2-methylidenetrimethylene carbonate. This one-pot synthesis protocol processed smoothly under mild reaction conditions. Moreover, a total of 28 examples, broad substrate scope, and high functional-group compatibility were observed. Preliminary mechanism studies were also conducted and demonstrated that the rhodium(III) catalyst played a vital role in the C-H-allylation and N-alkylation cyclization process.


Assuntos
Ródio , Alquilação , Carbonatos , Catálise , Ciclização
2.
Parasitol Res ; 116(2): 577-587, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27878389

RESUMO

The spleen is one of the most important peripheral immune organs, which is frequently affected in infectious diseases. Infectious diseases can induce splenic alterations including splenic atrophy and functional alteration, while splenic atrophy may in turn interferes with recovery of infectious diseases. Angiostrongyliasis is an infectious disease by Angiostrongylus cantonensis (A. cantonensis), which invade non-permissive hosts, such as humans and mice, to cause severe damage to the central nervous system (CNS) and acute inflammatory response. A. cantonensis infection-induced CNS injury has been confirmed to be due to profound immunopathology derived from peripheral immune components. However, the mechanism of immunopathology remains largely unknown. Here, we found that A. cantonensis invaded non-permissive hosts such as mice in the brain, but not in the other peripheral organs. However, this infection induced severe spleen atrophy. We further recognized that this atrophy is associated with a decrease of total splenocyte number and disruption of splenic structure due to reduced proliferation and increased apoptotosis. These also resulted in deterioration of T cell profile in the periphery with a low CD4/CD8 ratio and B/T cell ratio, and increased ratio of CD4+CD25+Foxp3+ Treg, CD8+CD28- T, and CD38+T lymphocyte of spleen. Albendazole treatment can alleviate spleen atrophy and set T cell immune reconstitution in some extend. Our data showed that A. cantonensis infection can cause splenic atrophy. These results are suggested to put more emphasis to improve the function of immune system. Meanwhile, infection and treatment model will be useful to evaluate new therapeutic approaches which can prevent or reverse immunosuppression and infectious complications.


Assuntos
Angiostrongylus cantonensis/fisiologia , Baço/imunologia , Infecções por Strongylida/imunologia , Angiostrongylus cantonensis/imunologia , Animais , Biomphalaria/parasitologia , Encéfalo/imunologia , Encéfalo/parasitologia , Encéfalo/patologia , Modelos Animais de Doenças , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Baço/parasitologia , Baço/patologia , Infecções por Strongylida/parasitologia , Infecções por Strongylida/patologia , Linfócitos T Reguladores/imunologia
3.
Infect Dis Poverty ; 5: 25, 2016 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-27025210

RESUMO

Schistosomiasis is an important zoonotic parasitic disease that causes serious harms to humans and animals. Surveillance and diagnosis play key roles in schistosomiasis control, however, current techniques for surveillance and diagnosis of the disease have limitations. As genome data for parasites are increasing, novel techniques for detection incorporating nucleotide sequences are receiving widespread attention. These sensitive, specific, and rapid detection methods are particularly important in the diagnosis of low-grade and early infections, and may prove to have clinical significance. This paper reviews the progress of nucleic acid detection in the diagnosis and prevention of schistosomiasis, including such aspects as the selection of target genes, and development and application of nucleic acid detection methods.


Assuntos
Técnicas de Amplificação de Ácido Nucleico/métodos , Schistosoma/isolamento & purificação , Esquistossomose/parasitologia , Animais , DNA de Helmintos/genética , Fezes/parasitologia , Humanos , Schistosoma/classificação , Schistosoma/genética , Esquistossomose/diagnóstico , Esquistossomose/prevenção & controle
4.
Parasitol Res ; 112(3): 1039-46, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23377146

RESUMO

Angiostrongyliasis, also known as eosinophils meningitis, is caused by Angiostrongylus cantonensis parasites in the human central nervous system. Currently, the drug of choice for treatment of angiostrongyliasis is albendazole, but dead worm lysis causes severe inflammatory response, which leads to central nervous system damage. Tribendimidine, a broad-spectrum anti-helmintic drug developed in China, is a derivative of amidantel. This study was designed to test the efficacy of tribendimidine against A. cantonensis in mice. We treated 65 infected female BALB/c mice with tribendimidine or albendazole by oral route. We observed that tribendimidine at doses of 50, 100 and 200 mg/kg/day was effective, and the worm reduction rates were 54.8 %,77.4 %, and 100 % compared with the control group. In addition, the therapeutic effect of early tribendimidine treatment (7 days post-infection [PI]) was better than the late treatment (14 days PI), in comparison with the albendazole group (20 mg/kg/day). The index of therapeutic efficacy included body weight, neurological function, survival time, worm reduction, mRNA levels of proinflammatory cytokines in brain tissue, histopathological examination and electron microscopy scanning. The results showed that tribendimidine could kill the larvae of A. cantonensis in the mice model, and the worm's body wall was observed to be damaged. After treatment with tribendimidine, the survival conditions such as body weight and neurological function were improved, and brain inflammation was reduced in infected mice. This study showed a strong efficacy of tribendimidine against A. cantonensis and provided suitable alternative treatments to further explore its potential use in treatment of human angiostrongyliasis.


Assuntos
Angiostrongylus cantonensis/efeitos dos fármacos , Anti-Helmínticos/administração & dosagem , Fenilenodiaminas/administração & dosagem , Infecções por Strongylida/tratamento farmacológico , Administração Oral , Albendazol/administração & dosagem , Animais , Modelos Animais de Doenças , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Carga Parasitária , Infecções por Strongylida/parasitologia , Análise de Sobrevida , Fatores de Tempo , Resultado do Tratamento
5.
Parasitol Res ; 112(3): 1261-72, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23319265

RESUMO

rSj16, a recombined protein from Schistosoma japonicum, has been identified as an anti-inflammatory molecule. In this study, we demonstrated that rSj16 strongly suppressed the growth of murine myeloid leukemia WEHI-3B JCS cells in a dose- and time-dependent manner. rSj16 induced apoptosis by increasing the proportion of sub-G1 apoptotic cells as well as causing cell cycle arrest at the G0/G1 phase. The expressions of cyclin D1, D2, D3, and E, and Cdk 2, 4, and 6 genes in WEHI-3B JCS cells were significantly down-regulated at 24 h as measured by real-time PCR. Furthermore, apoptosis induced by rSj16 was confirmed by 4,6-diamidino-2-phenylindole nuclear staining assay and annexin V/propidium iodide double staining. A reduction of the mitochondrial membrane potential indicated an active involvement of mitochondria in the apoptosis process. rSj16 treatment induced an increase in the activity of caspase 3, 6, and 9, and expression of pro-apoptotic Bax. Meanwhile, the decreased expression of anti-apoptotic Bcl-2 was observed after rSj16 treatment. Taken together, our results implied that rSj16 can inhibit proliferation by inducing G0/G1 cell cycle arrest and apoptosis of murine myeloid leukemia cells via activation of the caspase-mediated mechanism by regulating the expression of Bcl-2 family.


Assuntos
Apoptose , Pontos de Checagem do Ciclo Celular , Células Precursoras de Granulócitos/fisiologia , Proteínas de Protozoários/metabolismo , Schistosoma japonicum/patogenicidade , Fatores de Virulência/metabolismo , Animais , Linhagem Celular Tumoral , Perfilação da Expressão Gênica , Células Precursoras de Granulócitos/efeitos dos fármacos , Camundongos , Proteínas de Protozoários/genética , Reação em Cadeia da Polimerase em Tempo Real , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Schistosoma japonicum/genética , Fatores de Tempo , Fatores de Virulência/genética
6.
Parasitol Res ; 112(3): 933-43, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23224730

RESUMO

Galectin plays an important role in host-parasite interactions. In this study, we identified a novel gene encoding galectin-10 (AcGal-10) from the cDNA library of Angiostrongylus cantonensis and characterized its biological role in the parasite. Sequence and phylogeny analysis showed that AcGal-10 is related to other galectin family members with the conserved loci (H(84)-D(86)-R(88)-V(96)-N(98)-W(105)-E(108)-R(110)). The mRNA level of AcGal-10 was expressed in reactive oxygen stress radicals. We have identified two proteins of A. cantonensis galectin-10 gene, one of which was reported (AcGAL10-W) and the others is AcGAL-10-M. In addition, recombinant AcGal-10 (rAcGal-10) was constructed into the pGEX-4T-1 plasmid, purified, and finally confirmed by SDS-PAGE and LC-MS. Hemagglutination assay showed that the minimum concentration of rAcGAL10-W and rAcGAL10-M required for the hemagglutination of BALB/c mice erythrocyte was 25 µg/mL, and the carbohydrate-binding ability showed no difference between rAcGAL10-W and rAcGAL10-M. The mRNA levels of AcGal-10 were indeed expressed higher after stimulation with H(2)O(2) and recombinant A. cantonensis galectin-10. A mutation of AcGal-10 was also found, but there was no significant difference compared with the wild type. Furthermore, we also confirmed that recombinant AcGal-10 plays a role in the activation of the microglia. In conclusion, the report here showed that AcGal-10 may be an important molecule related to infection of A. cantonensis.


Assuntos
Angiostrongylus cantonensis/efeitos dos fármacos , Angiostrongylus cantonensis/fisiologia , Galectinas/biossíntese , Perfilação da Expressão Gênica , Estresse Oxidativo , Espécies Reativas de Oxigênio/toxicidade , Sequência de Aminoácidos , Animais , Eritrócitos/efeitos dos fármacos , Galectinas/genética , Hemaglutinação , Camundongos , Camundongos Endogâmicos BALB C , Modelos Moleculares , Dados de Sequência Molecular , Filogenia , Ligação Proteica , Conformação Proteica , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Ratos , Ratos Sprague-Dawley , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos
7.
Parasitol Res ; 112(1): 207-14, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23073569

RESUMO

Angiostrongylus cantonensis is a rodent nematode. Adult worms of A. cantonensis live in the pulmonary arteries of rats. Humans and mice are accidental hosts or named nonpermissive hosts. The larva cannot develop into an adult worm and only causes serious eosinophilic meningitis or meningoencephalitis if humans or mice eat food containing larva of A. cantonensis in the third stage. The differing consequences largely depend on differing immune responses of the host to parasite during A. cantonensis invasion and development. Microglia is considered to be the key immune cell in the central nervous system like macrophage. To further understand the reasons for why mice and rats attain different outcomes in A. cantonensis infection, we set up the method to isolate and culture newborn rats' primary microglia and observe the activation of the microglia cells, comparing with mice microglia cell line N9. We treated cells with soluble antigen of the fourth larva of A. cantonensis (L4 larva) and measured mRNA levels of IL-1ß, IL-5, IL-6, IL-13, eotaxin, iNOS, and TNF-α by real-time PCR. The results showed that N9 expressed high mRNA level of IL-6, IL-1ß, TNF-α, iNOS, IL-5, IL-13, and eotaxin, but primary microglia only had IL-5, IL-13, and eotaxin mRNA level. It implies that microglia from rats and mice had different reaction to soluble antigen of A. cantonensis. Therefore, we supposed that microglia may play an immune modulation role during the brain inflammation induced by A. cantonensis.


Assuntos
Angiostrongylus cantonensis/imunologia , Antígenos de Helmintos/imunologia , Microglia/imunologia , Microglia/parasitologia , Animais , Antígenos de Helmintos/isolamento & purificação , Células Cultivadas , Citocinas/biossíntese , Perfilação da Expressão Gênica , Larva/imunologia , Camundongos , Óxido Nítrico Sintase Tipo II/biossíntese , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase em Tempo Real
8.
J Biochem ; 148(3): 349-58, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20587646

RESUMO

The main protease of the coronavirus causing severe acute respiratory syndrome performs proteolytic processing of the viral polyproteins. The active form of the enzyme is a homodimer with each subunit consisting of three structural domains. Domains I and II, hosting the complete catalytic machinery, constitute the N-terminal chymotrypsin-like folding scaffold and connect to the extra C-terminal domain III by a long loop. Previously, the domain III-truncated enzyme was demonstrated to fold independently into an intact chymotrypsin-like fold, but it showed no enzyme activity. To further delineate the structure-function relationships of the domain III and the long loop, we generated some truncated and mutated M(pro) forms bearing various combinations of the loop with other structural parts of the enzyme. Their conformational and association properties were investigated in detail. Far-ultraviolet circular dichroism (CD) measurements revealed that these fragments could fold independently. The secondary, tertiary and quaternary structures of these mixtures were monitored by CD, fluorescence spectroscopy and analytical ultracentrifugation. However, no enzyme activity was observed for any mutant or mixtures. These observations indicate that the covalent linkage between the chymotrypsin like and the extra domain is essential for enzymatic activity of the main coronavirus protease and for the integrity of its quaternary structure.


Assuntos
Cisteína Endopeptidases/química , Vírus da SARS/enzimologia , Proteínas Virais/química , Quimotripsina , Proteases 3C de Coronavírus , Estrutura Quaternária de Proteína , Estrutura Terciária de Proteína , Subunidades Proteicas
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