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1.
Virulence ; 12(1): 2314-2326, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34490839

RESUMO

To resolve the growing problem of drug resistance in the treatment of bacterial and fungal pathogens, specific cellular targets and pathways can be used as targets for new antimicrobial agents. Endogenous riboflavin biosynthesis is a conserved pathway that exists in most bacteria and fungi. In this review, the roles of endogenous and exogenous riboflavin in infectious disease as well as several antibacterial agents, which act as analogues of the riboflavin biosynthesis pathway, are summarized. In addition, the effects of exogenous riboflavin on immune cells, cytokines, and heat shock proteins are described. Moreover, the immune response of endogenous riboflavin metabolites in infectious diseases, recognized by MHC-related protein-1, and then presented to mucosal associated invariant T cells, is highlighted. This information will provide a strategy to identify novel drug targets as well as highlight the possible clinical use of riboflavin.

2.
J Med Microbiol ; 70(8)2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34397349

RESUMO

Introduction. Lactococcus petauri LZys1 (L. petauri LZys1) is a type of lactic acid bacteria (LAB), which was initially isolated from healthy human gut.Hypothesis/Gap Statement. It was previously anticipated that L. petauri LZys1 has potential characteristics of probiotic properties. The genetic structure and the regulation functions of L. petauri LZys1 need to be better revealed.Aim. The aim of this study was to detect the probiotic properties L. petauri LZys1 and to reveal the genome information related to its genetic adaptation and probiotic profiles.Methodology. Multiple in vitro experiments were carried out to evaluate its lactic acid-producing ability, resistance to pathogenic bacterial strains, auto-aggregation and co-aggregation ability, and so on. Additionally, complete genome sequencing, gene annotation, and probiotic associated gene analysis were performed.Results. The complete genome of L. petauri LZys1 comprised of 1 985 765 bp, with a DNA G+C content of 38.07 %, containing 50 tRNA, seven rRNA, and four sRNA. A total of 1931 genes were classified into six functional categories by Kyoto Encyclopaedia of Genes and Genomes (KEGG) database. The neighbour-joining phylogeny tree based on the whole genome of L. petauri LZys1 and other probiotics demonstrated that L. petauri LZys1 has a significant similarity to Lactococcus garvieae. The functional genes were detected to expound the molecular mechanism and biochemical processes of its potential probiotic properties, such as atpB gene.Conclusion. All the results described in this study, together with relevant information previously reported, made L. prtauri LZys1 a very interesting potential strain to be considered as a prominent candidate for probiotic use.


Assuntos
Trato Gastrointestinal/microbiologia , Genoma Bacteriano , Lactococcus , Probióticos , Animais , Bactérias/crescimento & desenvolvimento , Bactérias/patogenicidade , Sequência de Bases , Fezes/microbiologia , Genes Bacterianos , Humanos , Lactococcus/citologia , Lactococcus/genética , Lactococcus/isolamento & purificação , Lactococcus/fisiologia , Masculino , Anotação de Sequência Molecular , Mariposas/microbiologia , Filogenia , Polissacarídeos Bacterianos/biossíntese , Polissacarídeos Bacterianos/genética , Sequenciamento Completo do Genoma , Adulto Jovem
3.
J Med Microbiol ; 70(3)2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33528353

RESUMO

Introduction. Since mcr-1 was first reported in China, there have been ten variants of MCR appearing nationwide so far. Multidrug-resistant Enterobacteriaceae bacteria carrying both NDM and MCR have become a serious threat to global public health.Hypothesis/Gap Statement. The genetic structure of mcr-9 needs to be better understood in order to better prevent and control the transmission of drug-resistant genes.Aims. The aim of this study was to characterize the presence of two Enterobacter hormaechei isolates, which carries bla NDM-5 CME2 and the coexistence of mcr-9 and bla NDM-1 strain CMD2, which were isolated from a patient with diabetes in Sichuan, China.Methodology. The microbroth dilution method was used for antibiotic susceptibility. Conjugation experiment was used to investigate the transferability of bla NDM-1, bla NDM-5 and mcr-9. Whole-genome sequencing was performed on Illumina HiSeq platform. The ability of biofilm formation was detected by crystal-violet staining, the virulence of the bacteria was measured by Galleria mellonella killing assay.Results. bla NDM-5 carrier CME2 and CMD2 with bla NDM-1 and mcr-9 were resistant to carbapenems, ß-lactam, aminoglycoside, quinolone and tetracycline, while CMD2 was also resistant to colistin. Conjugation assay and plasmid replicon typing further demonstrated that both bla NDM-1 and bla NDM-5 were respectively present on the self-transferrable IncX3 plasmid, mcr-9 was located on the self-transferrable IncHI2 plasmid. Through the analysis of mcr-9 gene context, the structure was DUF4942-rcnR-rcnA-copS-IS903-mcr-9-wbuC-qseC-qseB-IS1R-ΔsilR-IS903, bla NDM-1 context was IS3000-ΔISAba125-IS5-bla NDM-1-ble-trpF-groS-groL-insE-ΔIS26 structure, bla NDM-5 structure was IS3000-bla NDM-5-ble-trpF-dsbC-ΔIS26-umuD-ISKox3-tnpR-parA. Biofilm formation of CME2 was stronger than CMD2. There was no significant difference in virulence between the two strains.Conclusion. This study reveals two multiple drug-resistant E. hormaechei isolates from diabetes patient samples. E. hormaechei carrying two NDM-resistant genes is already a serious threat, where MCR is an important cause of treatment failure in bacterial infections. This study is a reminder not only to prevent infection in patients with diabetes, but also to constantly monitor the epidemic and spread of the drug-resistant gene.


Assuntos
Enterobacteriáceas Resistentes a Carbapenêmicos/isolamento & purificação , Coinfecção/microbiologia , Complicações do Diabetes/microbiologia , Enterobacter/isolamento & purificação , Infecções por Enterobacteriaceae/microbiologia , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Biofilmes/crescimento & desenvolvimento , Enterobacteriáceas Resistentes a Carbapenêmicos/efeitos dos fármacos , Enterobacteriáceas Resistentes a Carbapenêmicos/genética , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Farmacorresistência Bacteriana Múltipla/genética , Enterobacter/efeitos dos fármacos , Enterobacter/genética , Genoma Bacteriano/genética , Humanos , Masculino , Testes de Sensibilidade Microbiana , Plasmídeos/genética , Fatores de Virulência/genética , Adulto Jovem
4.
Microb Biotechnol ; 13(5): 1489-1501, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32395911

RESUMO

The GATA-type sexual development transcription factor NsdD has been implicated in virulence, secondary metabolism and asexual development in filamentous fungi. However, little is known about its function in the yeast-to-hypha transition and in microsclerotium formation. In the current study, the orthologous NsdD gene MrNsdD in the entomopathogenic fungus Metarhizium rileyi was characterized. Transcriptional analysis indicated that MrNsdD was involved in yeast-to-hypha transition, conidiation and microsclerotium formation. After targeted deletion of MrNsdD, dimorphic transition, conidiation, fungal virulence and microsclerotium formation were all impaired. Compared with the wild-type strain, the ΔMrNsdD mutants were hypersensitive to thermal stress. Furthermore, transcriptome sequencing analysis revealed that MrNsdD regulated a distinct signalling pathway in M. rileyi during the yeast-to-hypha transition or microsclerotium formation, but exhibited overlapping regulation of genes during the two distinct developmental stages. Taken together, characterization of the MrNsdD targets in this study will aid in the dissection of the molecular mechanisms of dimorphic transition and microsclerotium development.


Assuntos
Metarhizium , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Fatores de Transcrição GATA , Regulação Fúngica da Expressão Gênica , Metarhizium/genética , Metarhizium/metabolismo , Esporos Fúngicos/metabolismo , Virulência
5.
Open Med (Wars) ; 15: 266-273, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32292823

RESUMO

Matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF MS) has become one of the most popular methods for the rapid and cost-effective detection of clinical pathogenic microorganisms. This study aimed to evaluate and compare the diagnostic performance of MALDI-TOF MS with that of conventional approaches for the direct identification of pathogens from urine samples. A systematic review was conducted based on a literature search of relevant databases. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR) and area under the summary receiver operating characteristic (SROC) curve of the combined studies were estimated. Nine studies with a total of 3920 subjects were considered eligible and included in the meta-analysis. The pooled sensitivity was 0.85 (95% CI 0.79-0.90), and the pooled specificity was 0.93 (95% CI 0.82-0.97). The PLR and NLR were 11.51 (95% CI 4.53-29.26) and 0.16 (95% CI 0.11-0.24), respectively. The area under the SROC curve was 0.93 (95% CI 0.91-0.95). Sensitivity analysis showed that the results of this meta-analysis were stable. MALDI-TOF MS could directly identify microorganisms from urine samples with high sensitivity and specificity.

6.
Fungal Genet Biol ; 134: 103278, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31610212

RESUMO

Transmembrane proteins as sensors encoded by fungal genes activate specific intracellular signal pathways in response to stress cues to help the fungus survive in a changing environment. To better understand the role of the cell wall integrity (CWI) pathway in the entomopathogenic fungus Metarhizium rileyi, an ortholog encoding the transmembrane protein Mid2, MrMid2, was identified and characterized functionally. Transcriptional analysis indicated that MrMid2 was involved in dimorphic transition, conidiation, and microsclerotium formation. After a targeted deletion of MrMid2, all three traits were impaired. Compared with the wild-type strain, the △MrMid2 mutants were hypersensitive to thermal stress, and cell wall and oxidative stress. Insect bioassays revealed that △MrMid2 mutants had decreased virulence levels following topical (22.5%) and injection bioassays (38.7%). Furthermore, transcription analysis showed that other genes of the CWI pathway, with the exception of another major sensor protein encoding gene, MrWsc1, were down-regulated in △MrMid2 mutants. These results suggest that MrMid2 plays important roles in dimorphic transition, conidiation, the stress response, virulence, and microsclerotium development in M. rileyi.


Assuntos
Parede Celular/metabolismo , Proteínas Fúngicas/genética , Genes Fúngicos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Glicoproteínas de Membrana/genética , Metarhizium/genética , Metarhizium/patogenicidade , Estresse Oxidativo/genética , Esporos Fúngicos/crescimento & desenvolvimento , Animais , Deleção de Genes , Regulação Fúngica da Expressão Gênica , Hifas/crescimento & desenvolvimento , Plasmídeos/genética , Transdução de Sinais/genética , Spodoptera/microbiologia , Transcriptoma , Virulência
7.
Artigo em Inglês | MEDLINE | ID: mdl-31452874

RESUMO

Background: A carbapenem-resistant hypermucoviscous Klebsiella pneumoniae isolate was recovered from human sputum. Methods: Whole genome sequencing of this isolate was carried out to reveal its clonal background, antimicrobial resistance determinants and virulence factors. Virulence assays were performed using wax moth larvae. The transfer of bla NDM-5 between bacterial strains was tested using conjugation. 59 genome assemblies of ST29 K. pneumoniae and 230 IncX3 plasmids regardless of the carriage of resistance gene were employed for phylogenetic analysis, respectively. Results: The strain carried a virulence plasmid pVir-SCNJ1 bearing the virulence gene rmpA and exhibited a high virulence in wax moth. This hypervirulent strain belongs to sequence type 29 and carries bla NDM-5, which is located on a conjugative plasmid, designated pNDM5-SCNJ1, belonging to type IncX3. pNDM5-SCNJ1 was fully sequenced and shows high similarity with pNDM_MGR194, except some deletion inside the ISAba125 region. Phylogenetic analysis of IncX3 plasmids revealed that although bla NDM-5 can be evolved from bla NDM-1 via point mutations within some IncX3 plasmids, most of bla NDM-5-carrying IncX3 plasmids probably have acquired bla NDM-5 in multiple events. Conclusions: In this study, we characterized a bla NDM-5-positive hypervirulent K. pneumoniae of sequence type 29 in China. Our results highlight the need for active surveillance on this lineage of carbapenem-resistant K. pneumoniae.


Assuntos
Enterobacteriáceas Resistentes a Carbapenêmicos/patogenicidade , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/patogenicidade , Sequenciamento Completo do Genoma/métodos , beta-Lactamases/genética , Animais , Enterobacteriáceas Resistentes a Carbapenêmicos/genética , Enterobacteriáceas Resistentes a Carbapenêmicos/isolamento & purificação , Evolução Molecular , Transferência Genética Horizontal , Genoma Bacteriano , Humanos , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/isolamento & purificação , Mariposas/microbiologia , Filogenia , Plasmídeos/genética , Análise de Sequência de DNA , Escarro/microbiologia , Virulência
8.
PLoS One ; 14(4): e0214686, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30978196

RESUMO

BACKGROUND: The Gram-negative bacterium Kerstersia gyiorum, a potential etiological agent of clinical infections, was isolated from several human patients presenting clinical symptoms. Its significance as a possible pathogen has been previously overlooked as no disease has thus far been definitively associated with this bacterium. To better understand how the organism contributes to the infectious disease, we determined the complete genomic sequence of K. gyiorum SWMUKG01, the first clinical isolate from southwest China. RESULTS: The genomic data obtained displayed a single circular chromosome of 3, 945, 801 base pairs in length, which contains 3, 441 protein-coding genes, 55 tRNA genes and 9 rRNA genes. Analysis on the full spectrum of protein coding genes for cellular structures, two-component regulatory systems and iron uptake pathways that may be important for the success of the bacterial survival, colonization and establishment in the host conferred new insights into the virulence characteristics of K. gyiorum. Phylogenomic comparisons with Alcaligenaceae species indicated that K. gyiorum SWMUKG01 had a close evolutionary relationships with Alcaligenes aquatilis and Alcaligenes faecalis. CONCLUSIONS: The comprehensive analysis presented in this work determinates for the first time a complete genome sequence of K. gyiorum, which is expected to provide useful information for subsequent studies on pathogenesis of this species.


Assuntos
Alcaligenaceae/genética , Genoma Bacteriano , Infecções Respiratórias/patologia , Alcaligenaceae/classificação , Alcaligenaceae/isolamento & purificação , China , DNA Bacteriano/química , DNA Bacteriano/metabolismo , Humanos , Ferro/metabolismo , Lipopolissacarídeos/biossíntese , Filogenia , Infecções Respiratórias/microbiologia , Fatores de Virulência/genética
9.
Microb Pathog ; 124: 301-304, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30165112

RESUMO

Hypervirulent variants of klebsiella pneumoniae (hvKP), which cause serious infections not only healthy individuals, but also the immunocompromised patients, have been increasingly reported recently. One conjugation of a hypermucoviscous strian SWU01 co-carried the resistance gene blaKPC-2 and virulence gene iroN by the PCR detection from three carbapenem-resistance hvKP. To know the genetic context of this plasmid. The whole genome of this strain was sequenced. We got a 162,552-bp plasmid (pSWU01) which co-carried the resistance gene blaKPC-2 and virulence gene iroN. It is composed of a typical IncFII-type backbone, five resistance genes including blaCTX-M-65, blaKPC-2, blaSHV-12, blaTEM-1 and rmtB, and several virulence relevant factors including iroN, traT and toxin-antitoxin systems. The plasmid pSWU01 co-carrying the multidrug resistance determinants and virulence relevant factors from the hypermucoviscous K. pneumoniae represents a novel therapeutic challenge.


Assuntos
Proteínas de Bactérias/metabolismo , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/enzimologia , Fatores de Virulência/metabolismo , beta-Lactamases/metabolismo , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Humanos , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/genética , Metiltransferases/genética , Metiltransferases/metabolismo , Plasmídeos/genética , Plasmídeos/metabolismo , Transporte Proteico , Fatores de Virulência/genética , beta-Lactamases/genética
10.
PLoS One ; 12(6): e0180730, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28662212

RESUMO

Characterization of the feeding preferences of bivalve larvae would help improving the bivalve aquaculture and hatchery by providing appropriate microalgal diets. However, inaccurate and laborious identification and counting of microalgal species have challenged the selective feeding of bivalves. In the present study, we developed a highly specific and sensitive assay using quantitative polymerase chain reaction (qPCR) to assess the selective feeding of bivalve larvae based on species-specific primers targeting to microalgal 18S rDNA sequences. The assay exhibited good specificity. The detection limits of the qPCR assay were 769, 71, 781 and 21 18S rDNA copies for Chaetoceros calcitrans, Isochrysis galbana, Platymonas helgolandica and Nannochloropsis oculata, respectively. Using such assay, we found that C. calcitrans and I. galbana were preferentially ingested, whereas N. oculata was preferentially rejected in biodeposits of four bivalve species, Tegillarca gransa, Cyclina sinensis, Scapharca subcrenata and Sinonovacula constricta. Furthermore, our growth experiments revealed that C. calcitrans and I. galbana could significantly promote the shell growth, whereas feeding of N. oculata resulted in poorer growth of four bivalve species. These data indicated that qPCR might be useful in screening of efficient and reliable microalgal species for each bivalve species, leading to improved bivalve aquaculture and hatchery.


Assuntos
Bivalves/fisiologia , Comportamento Alimentar , Larva/fisiologia , Microalgas , Animais , Bivalves/crescimento & desenvolvimento , Reação em Cadeia da Polimerase em Tempo Real
11.
Parasitol Res ; 116(1): 377-385, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27796563

RESUMO

Paragonimiasis skrjabini is a kind of zoonosis and prevalent in 16 provinces in China, such as Chongqing, Fujian, Sichuan, and Yunnan. However, sensitive and efficient diagnostic methods for the infection are limited. In order to provide a more convenient and simple method for serologic diagnosis, the recombinant P. skrjabini cysteine protease (PsCP) was expressed, purified, and then used to develop an indirect enzyme-linked immunosorbent assay (ELISA) for detecting anti-PsCP antibodies in human. Given the positive/negative cutoff value as 0.606, the maximum dilution of human sera in which anti-PsCP antibodies could be detected was 1:12,800. In addition, the coefficients of variation (CVs) of inter-assay and intra-assay experiments were both below 10 %. Furthermore, the sensitivity of the PsCP-based ELISA was 95.5 %, and the indirect ELISA displays no cross-reactivity with human antisera against Echinococcus granulosus, Taenia solium, Schistosoma japonicum, and Trichinella spiralis, either. In conclusion, recombinant PsCP was readily produced and used to establish a simple PsCP-based ELISA that provided a highly specific and sensitive method for analysis of clinical samples. Besides, the method can also probably be used to diagnose P. skrjabini infection in animals.


Assuntos
Proteínas de Helminto/imunologia , Paragonimíase/diagnóstico , Paragonimíase/parasitologia , Paragonimus/isolamento & purificação , Proteínas Recombinantes , Animais , Anticorpos Anti-Helmínticos/sangue , Antígenos de Helmintos , China , Reações Cruzadas , Ensaio de Imunoadsorção Enzimática/métodos , Humanos , Soros Imunes/imunologia , Testes Imunológicos , Sensibilidade e Especificidade
12.
PLoS One ; 9(3): e92034, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24643068

RESUMO

BACKGROUND: Paragonimiasis is a food-borne trematodiasis, a serious public health issue and a neglected tropical disease. Paragonimus skrjabini is a unique species found in China. Unlike paragonimiasis westermani, it is nearly impossible to make a definitive diagnosis for paragonimiasis skrjabini by finding eggs in sputum or feces. Immunodiagnosis is the best choice to detect paragonimiasis skrjabini. There is an urgent need to develop a novel, rapid and simple immunoassay for large-scale screening patients in endemic areas. METHODOLOGY/PRINCIPAL FINDINGS: To develop a rapid, simple immunodiagnostic assay for paragonimiasis, rabbit anti-human IgG was conjugated to colloidal gold particles and used to detect antibodies in the sera of paragonimiasis patients. The synthesis and identification of colloidal gold particles and antibody-colloidal gold conjugates were performed. The size of colloidal gold particles was examined using a transmission electron microscope (TEM). The average diameter of colloidal gold particles was 17.46 nm with a range of 14.32-21.80 nm according to the TEM images. The formation of antibody-colloidal gold conjugates was monitored by UV/Vis spectroscopy. Excretory-secretory (ES) antigen of Paragonimus skrjabini was coated on nitrocellulose membrane as the capture line. Recombinant Staphylococcus protein A was used to prepare the control line. This rapid gold immunochromatographic strip was assembled in regular sequence through different accessories sticked on PVC board. The relative sensitivity and specificity of the strip was 94.4% (51/54) and 94.1% (32/34) respectively using ELISA as the standard method. Its stability and reproducibility were quite excellent after storage of the strip at 4°C for 6 months. CONCLUSIONS/SIGNIFICANCE: Immunochromatographic strip prepared in this study can be used in a rapid one-step immunochromatographic assay, which is instantaneous and convenient.


Assuntos
Anticorpos Anti-Helmínticos/química , Anticorpos Monoclonais/química , Cromatografia de Afinidade/métodos , Paragonimíase/diagnóstico , Paragonimus/isolamento & purificação , Animais , Anticorpos Anti-Helmínticos/imunologia , Anticorpos Monoclonais/imunologia , Cromatografia de Afinidade/normas , Coloides , Feminino , Ouro/química , Humanos , Paragonimíase/imunologia , Paragonimíase/parasitologia , Paragonimus/imunologia , Tamanho da Partícula , Coelhos , Fitas Reagentes , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
13.
Parasitol Int ; 61(4): 645-9, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22814214

RESUMO

Paragonimiasis has previously been reported in the Southwest Provinces of China, including Chongqing and Sichuan. The construction of Three Gorges Dam, which was begun in 1994, has resulted in substantial changes to the depth and the flow pattern of the Yangtze River. To investigate epidemiology of the paragonimiasis, 724 people aged 2-49 years were selected and examined for Paragonimus infection by intradermal test (IDT), and enzyme-linked immunosorbent assay (ELISA). A survey of eating habits was conducted face-to-face in 5 endemic counties. Freshwater crabs were collected from seven sites in the 5 counties to determine the rate of infection with Paragonimus metacercariae. Additionally, we analyzed 213 case reports from the region dated 2006 to 2009. According to the survey results, the prevalence of Paragonimus skrjabini infection in freshwater crab was 39.65%, and the human infection rates detected by IDT and ELISA were 14.36% (104/724) and 7.46% (54/724), respectively. These results show that the Three Gorges Reservoir is still an area of high paragonimiasis endemicity. The water level of the Yangtze River has risen to 175 m, and the area of water coverage in the region has increased to 1084 km(2). These conditions will favor the growth and expansion of the freshwater crab population.


Assuntos
Paragonimíase/parasitologia , Paragonimus/isolamento & purificação , Adolescente , Adulto , Animais , Braquiúros/parasitologia , Doenças do Gato/epidemiologia , Doenças do Gato/parasitologia , Gatos , Criança , Pré-Escolar , China/epidemiologia , Reservatórios de Doenças/parasitologia , Doenças do Cão/epidemiologia , Doenças do Cão/parasitologia , Cães , Ensaio de Imunoadsorção Enzimática , Interações Hospedeiro-Parasita , Humanos , Pessoa de Meia-Idade , Paragonimíase/epidemiologia , Adulto Jovem
14.
J Ethnopharmacol ; 103(2): 154-9, 2006 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-16198523

RESUMO

Astragalosides is the major active constituent of Radix Astragali. The present study was carried out to investigate the effect of crude astragalosides fraction (CAF) on rats liver fibrosis and its possible mechanisms. Hepatic fibrosis was induced by subcutaneous injection with 50% CCl(4) in Sprague-Dawley rats. The amount of CCl(4) administered was 1 mg kg(-1). The alanine aminotransferase (ALT), aspartate aminotransferase (AST) levels in plasma and hydroxyproline (Hyp), malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-px) contents in liver tissue were assayed by spectrophotometry. The hyaluronic acid (HA) and procollagen III (PC III) were assessed by radioimmunoassay. Tumor necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta1 (TGF-beta1) levels in culture supernatants of Kupffer cells (KCs) were determined with ELISA. Liver samples collected after 8 weeks of CCl(4) treatment were stained with hematoxylin-eosin (HE) and massion, and scored. Intragastric administration of CAF (10, 20 and 40 mg kg(-1)) significantly decreased indices of liver and spleen, the serum transaminase activities, HA and PC III levels, and Hyp and MDA contents in liver tissue in rats of hepatic fibrosis. Decreased SOD and GSH-px levels were reversed after administration of CAF. Histopathological scores showed CAF had inhibitory effect on the progression of hepatic fibrosis. In the in vitro experiments, CAF significantly reduced TNF-alpha and TGF-beta1 levels in culture supernatants of KCs. The results showed CAF significantly inhibited the progression of hepatic fibrosis induced by CCl(4), and the inhibitory effect of CAF on hepatic fibrosis might be associated with its ability to scavenge free radical and inhibit the production of TNF-alpha and TGF-beta1 from activated KCs.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Cirrose Hepática Experimental/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Animais , Macrófagos do Fígado/efeitos dos fármacos , Macrófagos do Fígado/metabolismo , Cirrose Hepática Experimental/enzimologia , Cirrose Hepática Experimental/metabolismo , Masculino , Raízes de Plantas , Ratos , Ratos Sprague-Dawley , Fator de Crescimento Transformador beta/metabolismo , Fator de Crescimento Transformador beta1 , Fator de Necrose Tumoral alfa/metabolismo
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