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1.
Front Microbiol ; 14: 1137369, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37065141

RESUMEN

Background: Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is associated with high mortality rates. Viral and bacterial coinfection is the primary cause of AECOPD. How coinfection with these microbes influences host inflammatory response and the gut microbiota composition is not entirely understood. Methods: We developed a mouse model of AECOPD by cigarette smoke exposure and sequential infection with influenza H1N1 virus and non-typeable Haemophilus influenzae (NTHi). Viral and bacterial titer was determined using MDCK cells and chocolate agar plates, respectively. The levels of cytokines, adhesion molecules, and inflammatory cells in the lungs were measured using Bio-Plex and flow cytometry assays. Gut microbiota was analyzed using 16S rRNA gene sequencing. Correlations between cytokines and gut microbiota were determined using Spearman's rank correlation coefficient test. Results: Coinfection with H1N1 and NTHi resulted in more severe lung injury, higher mortality, declined lung function in COPD mice. H1N1 enhanced NTHi growth in the lungs, but NTHi had no effect on H1N1. In addition, coinfection increased the levels of cytokines and adhesion molecules, as well as immune cells including total and M1 macrophages, neutrophils, monocytes, NK cells, and CD4 + T cells. In contrast, alveolar macrophages were depleted. Furthermore, coinfection caused a decline in the diversity of gut bacteria. Muribaculaceae, Lactobacillus, Akkermansia, Lachnospiraceae, and Rikenella were further found to be negatively correlated with cytokine levels, whereas Bacteroides was positively correlated. Conclusion: Coinfection with H1N1 and NTHi causes a deterioration in COPD mice due to increased lung inflammation, which is correlated with dysbiosis of the gut microbiota.

2.
Front Genet ; 13: 878607, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35646080

RESUMEN

Objective: We identify and explore the candidate susceptibility genes for cirrhosis and their underlying biological mechanism. Methods: We downloaded the genome-wide association studies summary data of 901 cirrhosis cases and 451,363 controls and integrated them with reference models of five potential tissues from the Genotype-Tissue Expression (GTEx) Project, including whole blood, liver, pancreas, spleen, and thyroid, to identify genes whose expression is predicted to be associated with cirrhosis. Then, we downloaded gene expression data of individuals with hepatocellular carcinoma from TCGA database to conduct differential expression analysis to validate these identified genes and explored their possible role in driving cirrhosis via functional enrichment and gene set enrichment analysis (GSEA). Results: We identified 10 significant genes (SKIV2L, JPH4, UQCC2, RP11-91I8.3, MAU2, ERAP1, PUS3, ZNF677, ARHGAP40, and SHANK3) associated with cirrhosis at a Bonferroni-corrected threshold of p < 0.01, among which two (SKIV2L and JPH4) were identified in the liver and five (SKIV2L, JPH4, MAU2, SHANK3, and UQCC2) were validated by differential expression analysis at an FDR-corrected threshold of p < 0.01. The enrichment analysis showed that the degradation process of RNA, which is enriched by 58 genes, is significantly under-enriched in liver cancer tissues (p = 0.0268). Conclusion: We have identified several candidate genes for cirrhosis in multiple tissues and performed differential genetic analysis using the liver cancer database to verify the significant genes. We found that the genes SKIV2L and JPH4 identified in the liver are of particular concern. Finally, through enrichment analysis, we speculate that the process of mRNA transcription and RNA degradation may play a role in cirrhosis.

3.
Infect Dis Poverty ; 10(1): 101, 2021 Jul 21.
Artículo en Inglés | MEDLINE | ID: mdl-34289905

RESUMEN

BACKGROUND: Eradication of infectious disease is the sanctified public health and sustainable development goal around the world. MAIN BODY: Three antimalarial barriers were developed to control imported malarial cases, and an effective surveillance strategy known as the "1-3-7 approach" was developed to eliminate malaria from the Chinese population. From 2011 to 2019, 5254 confirmed malaria cases were reported and treated in Yunnan Province, China. Among them, 4566 cases were imported from other countries, and 688 cases were indigenous from 2011 to 2016. Since 2017, no new local malarial case has been reported in China. Thus, malaria has been completely eliminated in Yunnan Province. However, malaria is detected in overseas travellers on a regular basis, such as visitors from neighbouring Myanmar. CONCLUSION: Hence, the strategies should be further strengthened to maintain a robust public health infrastructure for disease surveillance and vector control programs in border areas. Such programs should be supported technically and financially by the government to avert the possibility of a malarial resurgence in Yunnan Province.


Asunto(s)
Malaria , China/epidemiología , Gobierno , Humanos , Malaria/epidemiología , Malaria/prevención & control , Mianmar , Salud Pública
4.
Phytochemistry ; 190: 112842, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34214924

RESUMEN

A phytochemical investigation on the flowers of Sophora davidii resulted in the isolation of three unusual matrine-adenine hybrids, sophovicines A-C, together with biogenetically related analogue sophocarpine. Their structures and absolute configurations were determined by NMR analysis, single-crystal X-ray diffraction, and electronic circular dichroism (ECD) data. Since sophovicines represent the first example of matrine-adenine hybrids, a putative biosynthetic pathway toward sophovicines A-C was proposed. In addition, computational molecular modeling suggested that compounds sophovicines B and C may have potent activities against human cytomegalovirus (HCMV). So, the inhibit effects of isolates on HCMV were evaluated. The results show that sophovicines B and C can inhibit HCMV replication effectively with IC50 values of 7.12 and 7.32 µM, respectively.


Asunto(s)
Sophora , Adenina/farmacología , Alcaloides , Citomegalovirus , Humanos , Estructura Molecular , Quinolizinas/farmacología , Matrinas
5.
Foodborne Pathog Dis ; 18(9): 640-646, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34292761

RESUMEN

Escherichia coli, Staphylococcus aureus, Shigella, Pseudomonas aeruginosa, and Klebsiella pneumoniae are common foodborne pathogens. In this study, the light-induced PMAxx-coupled multiplex PCR (PMAxx-mPCR) was established to detect the aforementioned five foodborne pathogens in fresh juice at the same time. Moreover, PMAxx pretreatment could effectively distinguish live bacteria from dead bacteria. The optimized PMAxx pretreatment conditions were incubation with a final concentration of 10 µmol/L PMAxx for 10 min and then photolysis for 8 min. After PMAxx pretreatment, the difference in Ct values with or without PMAxx was determined by quantitative real-time PCR. The results showed a significant difference in Ct value before and after PMAxx treatment. Finally, the bacteria-contaminated fresh juice samples treated with PMAxx dye were detected by mPCR. The detection limit of PMAxx-mPCR was 102 colony-forming units (CFU)/mL for E. coli, Shigella, P. aeruginosa, and K. pneumoniae and 103 CFU/mL for S. aureus. Compared with mPCR detection of samples without PMAxx treatment, the proposed method solved the false-positive problem due to dead bacteria. Hence, an accurate and efficient method for the simultaneous detection of five types of pathogenic bacteria was established. This method could be applied to analytical procedures for ensuring food safety.


Asunto(s)
Reacción en Cadena de la Polimerasa Multiplex , Staphylococcus aureus , Bacterias/genética , Escherichia coli , Microbiología de Alimentos , Reacción en Cadena en Tiempo Real de la Polimerasa , Staphylococcus aureus/genética
6.
ACS Omega ; 5(16): 9301-9310, 2020 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-32363280

RESUMEN

Antimicrobial peptides (AMPs) are a class of templates with application potential for drug development. Amphibians are important sources of AMPs. Duttaphrynus melanostictus is the main source of traditional Chinese medicine "Chansu", which has anti-infection effect while without a clear mechanism. This study aimed to find the cathelicidin peptide in D. melanostictus and then investigate the activity in vivo and in vitro, and an AMP-encoding gene (cathelicidin-DM, GenBank: KJ820824.1) was obtained from the constructed cDNA library of D. melanostictus. The MIC test and SYTOX Green uptake were used for the evaluation of the bactericidal capacity and mechanisms. The serum stability tests were used for the evaluation of the application potential. The skin wound infection model and in vivo imaging were used for in vitro application of possibility evaluation. The results showed that cathelicidin-DM was a 37 amino acid AMP with good bactericidal ability, which was similar to melittin: both can kill bacteria within 15 min. Moreover, cathelicidin-DM exhibits good therapeutic potential in the mouse wound infection model, and it can be enriched to the site of infection for treatment. Thus, cathelicidin-DM could be a new template for antimicrobial drug development given its good antibacterial activity in vivo and in vitro.

7.
Braz J Microbiol ; 50(4): 961-967, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31456171

RESUMEN

Klebsiella pneumoniae belongs to Enterobacteriaceae, which is the commonest bacterium causing nosocomial respiratory tract infection. It ranks second in bacteremia and urinary tract infection in gram-negative bacteria. Therefore, the rapid and accurate identification of K. pneumoniae was of great significance for the guide of clinical medication, and timely treatment of patients. The purpose of this study was to establish a rapid and sensitive molecular detection method for K. pneumoniae based on loop-mediated isothermal amplification (LAMP) technology. Firstly, local BLAST and NCBI BLAST were used to analyze the genome of K. pneumoniae. According to the principle of interspecific and intraspecific specificity, CelB (GenBank ID 11847805) was selected as the specific gene. Then, the LAMP and PCR identification systems were established with this target gene. Thirty-six clinical isolates of K. pneumoniae and 50 non-K. pneumoniae were used for the specific evaluation, and both LAMP and PCR could specifically distinguish K. pneumoniae from non-K. pneumoniae. A 10-fold series diluted positive plasmids and simulated infected blood samples were used as the templates in the sensitivity assay, and the results showed that the sensitivity could reach 1 copy/reaction. In summary, a rapid, specific, and sensitive LAMP method was established to detect K. pneumoniae in clinics.


Asunto(s)
Proteínas Bacterianas/genética , Técnicas de Tipificación Bacteriana/métodos , Infecciones por Klebsiella/microbiología , Klebsiella pneumoniae/aislamiento & purificación , Técnicas de Amplificación de Ácido Nucleico/métodos , Bacteriemia/diagnóstico , Bacteriemia/microbiología , Cartilla de ADN/genética , Humanos , Infecciones por Klebsiella/diagnóstico , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/metabolismo , Plásmidos/genética , Sensibilidad y Especificidad
8.
Clin Lab ; 65(4)2019 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-30969069

RESUMEN

BACKGROUND: Escherichia coli is the most common pathogenic bacteria that frequently causes life-threatening opportunistic human infections, diarrhea, and septicemia in immunocompromised hosts. METHODS: This study aimed to establish a loop-mediated isothermal amplification (LAMP) method for the rapid and sensitive detection of a hypothetical protein from an E. coli-specific gene (GenBank ID: 13702648). The gene was obtained through local and online BLAST, and specific primers were designed for this gene. Reaction conditions were optimized at 65ºC for 30 minutes and 80ºC for 2 minutes, whereas the reaction system contained 5.2 mM Mg2+, 8 U of Bst 2.0 DNA polymerase, 1.4 mM deoxyribonucleotide, and 0.2 and 1.6 µM of the outer and inner primers, respectively. The LAMP method was evaluated using 240 strains of E. coli and 150 strains of non-E. coli. RESULTS: Positive reactions were observed on all 240 strains of E. coli while all non-E. coli strains were negative. Plasmids with the specific gene and mice blood with E. coli were used for sensitivity analysis. The detection limit of LAMP was 100 bacterium/reaction. CONCLUSIONS: Results showed that the LAMP targeted to the hypothetical protein (GenBank ID: 13702648) is a fast, specific, sensitive, inexpensive, and suitable method for the detection of E. coli.


Asunto(s)
Técnicas de Laboratorio Clínico/métodos , Escherichia coli/genética , Técnicas de Amplificación de Ácido Nucleico , Animales , Cartilla de ADN/genética , Diarrea/microbiología , Humanos , Huésped Inmunocomprometido , Límite de Detección , Ratones , Plásmidos/genética , Reacción en Cadena de la Polimerasa , Reproducibilidad de los Resultados , Sensibilidad y Especificidad
9.
Virol Sin ; 34(3): 270-277, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-30989428

RESUMEN

As a universal pathogen leading to neonatal defects and transplant failure, human cytomegalovirus (HCMV) has strict species specificity and this has prevented the development of a suitable animal model for the pathogenesis study. The mechanism of cross-species barrier remains elusive and there are so far no non-human cell culture models that support HCMV replication. The Chinese tree shrew (Tupaia belangeri chinensis) is a small laboratory animal and evolutionary closely related with primates. We investigated the susceptibility of primary tree shrew dermis fibroblasts (TSDF) to HCMV infection. Infection with a GFP-expressing HCMV virus resulted in green fluorescence in infected cells with the expression of IE1, UL44 and pp28. The titers of cell-free viruses reached 103 PFU/mL at 96 hpi, compared to titers of 104 PFU/mL observed in primary human foreskin fibroblasts. Our results suggested that TSDF was semi-permissive for HCMV infection. The TSDF model could be further used to investigate key factors influencing cross-species multiplication of HCMV.


Asunto(s)
Citomegalovirus/fisiología , Dermis/virología , Fibroblastos/virología , Musarañas , Animales , Células Cultivadas , Cromosomas Artificiales Bacterianos , Dermis/citología , Modelos Animales de Enfermedad , Fluorescencia , Prepucio/citología , Prepucio/virología , Proteínas Fluorescentes Verdes , Humanos , Masculino , Especificidad de la Especie , Replicación Viral
10.
Emerg Microbes Infect ; 8(1): 232-241, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30866776

RESUMEN

Zika virus (ZIKV) is a mosquito-borne flavivirus that caused the public health emergency. Recently, we have proved a novel small animal tree shrew was susceptive to ZIKV infection and presented the most common rash symptoms as ZIKV patients. Here we further cultured the primary cells from different tissues of this animal to determine the tissue tropism of ZIKV infection in vitro. The results showed that the primary cells from tree shrew kidney, lung, liver, skin and aorta were permissive to ZIKV infection and could support viral replication by the detection of viral specific RNA intra- and extra-cells. In comparing, the skin fibroblast and vascular endothelial cells were highly permissive to ZIKV infection with high releasing of active virus particles in supernatants proved by its infectivity in established neonatal mouse model. The expressions of ZIKV envelop and nonstructural protein-1, and the effects and strong immune response of primary tree shrew cells were also detected followed by ZIKV infection. These findings provide powerful in vitro cell-level evidence to support tree shrew as animal model of ZIKV infection and may help to explain the rash manifestations in vivo.


Asunto(s)
Modelos Animales de Enfermedad , Tupaiidae/virología , Infección por el Virus Zika/virología , Virus Zika/patogenicidad , Animales , Aorta/citología , Aorta/virología , Células Cultivadas , Chlorocebus aethiops , Células HEK293 , Células Endoteliales de la Vena Umbilical Humana , Humanos , Riñón/citología , Riñón/virología , Hígado/citología , Hígado/virología , Pulmón/citología , Pulmón/virología , Piel/citología , Piel/virología , Células Vero , Replicación Viral
11.
Exp Ther Med ; 17(1): 131-136, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30651773

RESUMEN

Pseudomonas aeruginosa is one of the three most pathogenic bacteria that frequently cause life-threatening opportunistic human infections, pneumonia, and lower respiratory tract infections in immunocompromised hosts, particularly in the burns ward. The present study aimed to establish a loop-mediated isothermal amplification (LAMP) method for the rapid and sensitive detection of P. aeruginosa-specific gene hypothetical protein (GenBank ID: 882161). The gene was obtained through local and online BLAST, and specific primers were designed for this gene. Reaction conditions were optimized at 65°C for 30 min and 80°C for 2 min, whereas the reaction system contained 5.2 mM Mg2+, 8 U Bst 2.0 DNA polymerase, 1.4 mM deoxyribonucleotide and 0.2 and 1.6 µM of the outer and inner primers, respectively. The LAMP method was evaluated using 150 P. aeruginosa and 170 non-P. aeruginosa strains. Positive reactions were observed on 150 P. aeruginosa strains, whereas all non-P. aeruginosa strains exhibited negative results. Plasmids with the specific gene and mouse blood with P. aeruginosa were used for sensitivity assay. The detection limit of LAMP was 1 bacterium/reaction. Results indicated that the LAMP method targeted to hypothetical protein is a fast, specific, sensitive, inexpensive and suitable method for detection of P. aeruginosa.

12.
J Med Virol ; 91(6): 1097-1103, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-30633820

RESUMEN

AIMS: To investigate the association between two RIG-I-like receptor gene polymorphisms and hepatitis C virus (HCV) infection in Chinese Han population. METHODS: The current study genotyped two selected SNPs (IFIH1 rs3747517 and DDX58 rs9695310) using TaqMan allelic discrimination assay to assess their association with the susceptibility and clinical outcome of HCV infection among 3065 participants (1545 non-HCV infection individuals, 568 spontaneous HCV clearance cases, and 952 persistent infection patients). RESULTS: IFIH1 rs3747517 (dominant model: Adjusted odds ratio [OR] = 1.34, 95% confidence interval [CI] = 1.07-1.68; P = 0.009) and DDX58 rs9695310 (dominant model: Adjusted OR = 1.43, 95% CI = 1.15-1.78; P = 0.001) were associated with chronic hepatitis C (CHC). And the risk of CHC increased when people were carrying more unfavorable rs3747517-GA/AA and rs9695310-GC/CC genotypes from zero to two with the chronic rates of 56.72%, 59.38%, and 69.01%, respectively (Ptrend < 0.001). CONCLUSION: Genetic variations at IFIH1 rs3747517 and DDX58 rs9695310 were independent predictors of chronic hepatitis C in Chinese Han population.


Asunto(s)
Proteína 58 DEAD Box/genética , Predisposición Genética a la Enfermedad , Hepatitis C Crónica/etnología , Hepatitis C Crónica/genética , Helicasa Inducida por Interferón IFIH1/genética , Adulto , Anciano , Alelos , Pueblo Asiatico/etnología , Pueblo Asiatico/estadística & datos numéricos , Estudios de Casos y Controles , China , Femenino , Variación Genética , Genotipo , Hepacivirus , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Receptores Inmunológicos
13.
Gene ; 679: 405-411, 2018 Dec 30.
Artículo en Inglés | MEDLINE | ID: mdl-30218750

RESUMEN

Vitamin D binding protein (VDBP) plays an important role in the immune modulation and pathogenesis of hepatitis C viral (HCV) infection by influencing serum vitamin D levels. The present study aims to evaluate the association of VDBP genetic polymorphisms with susceptibility to and chronicity of HCV infection in a high-risk Chinese population. Seven genetic variants in the VDBP gene were genotyped in a case-control study of 886 patients with HCV persistent infection, 539 subjects with spontaneous clearance, and 1081 uninfected controls. Logistic regression analysis was used to assess the effects of these variants on HCV infection outcomes. The results showed that two variants rs7041-G and rs3733359-T alleles were significantly associated with increased susceptibility of HCV infection, and the combined effect of the two unfavorable alleles was related to an elevated risk of HCV infection in a locus-dosage manner (Ptrend = 8.16 × 10-4). Interaction analysis manifested that rs7041-GT/GG and rs3733359-CT/TT jointly increased risk of HCV infection. Moreover, haplotype analysis suggested that compared with the most frequent TC haplotype, the haplotype carrying GT indicated a risk effect of HCV infection [odds ratio (OR) = 1.464]. However, no significant associations were observed for the other five variants. These findings implied that VDBP rs7041-G and rs3733359-T variants may contribute to increased susceptibility to HCV infection in a high-risk Chinese population.


Asunto(s)
Pueblo Asiatico/genética , Hepatitis C/genética , Polimorfismo de Nucleótido Simple , Proteína de Unión a Vitamina D/genética , Adulto , Anciano , Estudios de Casos y Controles , China , Femenino , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Haplotipos , Humanos , Masculino , Persona de Mediana Edad
14.
Mol Neurodegener ; 12(1): 38, 2017 05 12.
Artículo en Inglés | MEDLINE | ID: mdl-28499404

RESUMEN

BACKGROUND: Herpes simplex virus type 1 strain 129 (H129) has represented a promising anterograde neuronal circuit tracing tool, which complements the existing retrograde tracers. However, the current H129 derived tracers are multisynaptic, neither bright enough to label the details of neurons nor capable of determining direct projection targets as monosynaptic tracer. METHODS: Based on the bacterial artificial chromosome of H129, we have generated a serial of recombinant viruses for neuronal circuit tracing. Among them, H129-G4 was obtained by inserting binary tandemly connected GFP cassettes into the H129 genome, and H129-ΔTK-tdT was obtained by deleting the thymidine kinase (TK) gene and adding tdTomato coding gene to the H129 genome. Then the obtained viral tracers were tested in vitro and in vivo for the tracing capacity. RESULTS: H129-G4 is capable of transmitting through multiple synapses, labeling the neurons by green florescent protein, and visualizing the morphological details of the labeled neurons. H129-ΔTK-tdT neither replicates nor spreads in neurons alone, but transmits to and labels the postsynaptic neurons with tdTomato in the presence of complementary expressed TK from a helper virus. H129-ΔTK-tdT is also capable to map the direct projectome of the specific neuron type in the given brain regions in Cre transgenic mice. In the tested brain regions where circuits are well known, the H129-ΔTK-tdT tracing patterns are consistent with the previous results. CONCLUSIONS: With the assistance of the helper virus complimentarily expressing TK, H129-ΔTK-tdT replicates in the initially infected neuron, transmits anterogradely through one synapse, and labeled the postsynaptic neurons with tdTomato. The H129-ΔTK-tdT anterograde monosynaptic tracing system offers a useful tool for mapping the direct output in neuronal circuitry. H129-G4 is an anterograde multisynaptic tracer with a labeling signal strong enough to display the details of neuron morphology.


Asunto(s)
Colorantes Fluorescentes , Proteínas Fluorescentes Verdes , Vías Nerviosas/citología , Neuronas/citología , Coloración y Etiquetado/métodos , Animales , Herpesvirus Humano 1 , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos
15.
Kaohsiung J Med Sci ; 33(5): 224-228, 2017 May.
Artículo en Inglés | MEDLINE | ID: mdl-28433068

RESUMEN

Glucose-stimulated insulin secretion (GSIS) is one of the important physiological characteristics of islet ß cells, and extracellular-regulated protein kinase 1/2 (ERK1/2) is an important member of the mitogen-activated protein kinase family that regulates this process. The inflammatory cytokine interleukin (IL)-1ß can inhibit the insulin secretion of pancreatic ß cells, but the exact mechanism is unclear. This study was designed to investigate the inhibitory effect of IL-1ß on GSIS in ßTC-6 cells and its relation with the ERK1/2 signal transduction pathway. ß-TC6 cells were cultured and stimulated with 0mM, 1.38mM, or 5.5mM glucose. In addition, GSIS in ß-TC6 cells was blocked by IL-1ß at concentrations of 0.15 ng/mL, 1.5 ng/mL, and 15 ng/mL. After glucose stimulation and IL-1ß intervention, the insulin level in the cell supernatant was detected by radioimmunoassay, and the phosphorylation level of ERK1/2 was detected by western blotting assay. The insulin level in the 1.38mM glucose group was 108.52 ± 5.94 uIU/mL, which was significantly higher than the 0mM and 5.5mM glucose groups (p < 0.05). Compared with the 0mM glucose group, the level of ERK1/2 phosphorylation was increased in the 1.38mM and 5.5mM glucose groups. After intervention by 0.15 ng/mL, 1.5 ng/mL, and 15 ng/mL IL-1ß, the level of ERK1/2 phosphorylation induced by 1.38mM glucose stimulation decreased in a dose-dependent manner, and the insulin level correspondingly decreased. IL-1ß can inhibit GSIS in ßTC-6 cells, which is related to its inhibition of the phosphorylation of ERK1/2.


Asunto(s)
Glucosa/farmacología , Insulina/metabolismo , Interleucina-1beta/farmacología , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , Animales , Línea Celular , Secreción de Insulina , Ratones , Fosforilación/efectos de los fármacos , Radioinmunoensayo , Transducción de Señal/efectos de los fármacos
16.
Arch Pharm Res ; 39(6): 771-7, 2016 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-27138284

RESUMEN

Two new ursane-type triterpenoid saponins, bodiniosides M (1) and N (2), along with three known saponins, oblonganosides I (3), pseudobuxussaponin B (4) and bodinioside A (5), were isolated from the aerial parts of Elsholtzia bodinieri. The structures of compounds 1 and 2 were characterized by spectroscopic data as well as acid hydrolysis and GC analysis as 3-O-ß-D-xylopyranosyl-19α-hydroxy-23-acetoxy-urs-12(13)-en-28-oic acid 28-O-α-L-rhamnopyranosyl-(1-2)-ß-D-glucopyranoside and 3-O-ß-D-glucopyranosyl-2α,19α-dihydroxy-urs-12(13)-en-28,20ß-lactone. Compounds 1 and 5 exhibited potent anti-HCV activities in vitro with a selective index of 6.53 and 4.41, respectively.


Asunto(s)
Antivirales/aislamiento & purificación , Descubrimiento de Drogas/métodos , Lamiaceae/química , Saponinas/aislamiento & purificación , Triterpenos/aislamiento & purificación , Animales , Antivirales/farmacología , Línea Celular , Supervivencia Celular/efectos de los fármacos , Hepacivirus/efectos de los fármacos , Estructura Molecular , Componentes Aéreos de las Plantas/química , Saponinas/farmacología , Triterpenos/farmacología
17.
Nat Prod Res ; 30(20): 2278-84, 2016 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-27093392

RESUMEN

A new flavonoid glycoside, eriodictyol 7-O-(6″-caffeoyl)-ß-D-glucopyranoside (1), along with 14 known compounds, were isolated from the whole plants of Elsholtzia bodinieri. All of the structures were determined by spectroscopic methods and chemical transformation. Compound 1 and luteolin (9) exhibited potent anti-HCV activities with a selective index of 135.85 and 20.84, respectively.


Asunto(s)
Flavonas/aislamiento & purificación , Flavonas/farmacología , Flavonoides/aislamiento & purificación , Flavonoides/farmacología , Glucósidos/aislamiento & purificación , Glucósidos/farmacología , Lamiaceae/química , Antivirales/química , Antivirales/farmacología , Evaluación Preclínica de Medicamentos/métodos , Flavonoides/química , Glicósidos/química , Glicósidos/aislamiento & purificación , Glicósidos/farmacología , Hepacivirus/efectos de los fármacos , Luteolina/farmacología , Estructura Molecular
18.
Immunology ; 147(4): 443-52, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26725773

RESUMEN

Human/simian immunodeficiency virus (HIV/SIV) infection can cause severe depletion of CD4(+) T cells in both plasma and mucosa; it also results in damage to the gut mucosa barrier, which makes the condition more conducive to microbial translocation. In this study, we used SIV-infected Chinese rhesus macaques to quantify the extent of microbial translocation and the function of immune cells in the entire gastrointestinal tract and to compare their differences between rapid and slow progressors. The results showed that in the slow progressors, microbial products translocated considerably and deeply into the lamina propria of the gut; the tissue macrophages had no significant differences compared with the rapid progressors, but there was a slightly higher percentage of mucosal CD8(+) T cells and a large amount of extracellular microbial products in the lamina propria of the intestinal mucosa of the slow progressors. The data suggested that although microbial translocation increased markedly, the mucosal macrophages and CD8(+) T cells were insufficient to clear the infiltrated microbes in the slow progressors. Also, therapies aimed at suppressing the translocation of microbial products in the mucosa could help to delay the progression of SIV disease.


Asunto(s)
Microbioma Gastrointestinal , Mucosa Intestinal/citología , Mucosa Intestinal/inmunología , Síndrome de Inmunodeficiencia Adquirida del Simio/inmunología , Síndrome de Inmunodeficiencia Adquirida del Simio/virología , Virus de la Inmunodeficiencia de los Simios/inmunología , Animales , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Progresión de la Enfermedad , Mucosa Intestinal/microbiología , Mucosa Intestinal/patología , Mucosa Intestinal/virología , Recuento de Linfocitos , Macaca mulatta , Macrófagos/inmunología , Macrófagos/metabolismo , Masculino , Fagocitosis/inmunología , Carga Viral
19.
Int J Mol Med ; 36(6): 1479-86, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26458567

RESUMEN

Dilated cardiomyopathy (DCM) is a major cause of sudden cardiac death and heart failure, and it is characterized by genetic and clinical heterogeneity, even for some patients with a very poor clinical prognosis; in the majority of cases, DCM necessitates a heart transplant. Genetic mutations have long been considered to be associated with this disease. At present, mutations in over 50 genes related to DCM have been documented. This study was carried out to elucidate the characteristics of gene mutations in patients with DCM. The candidate genes that may cause DCM include MYBPC3, MYH6, MYH7, LMNA, TNNT2, TNNI3, MYPN, MYL3, TPM1, SCN5A, DES, ACTC1 and RBM20. Using next-generation sequencing (NGS) and subsequent mutation confirmation with traditional capillary Sanger sequencing analysis, possible causative non-synonymous mutations were identified in ~57% (12/21) of patients with DCM. As a result, 7 novel mutations (MYPN, p.E630K; TNNT2, p.G180A; MYH6, p.R1047C; TNNC1, p.D3V; DES, p.R386H; MYBPC3, p.C1124F; and MYL3, p.D126G), 3 variants of uncertain significance (RBM20, p.R1182H; MYH6, p.T1253M; and VCL, p.M209L), and 2 known mutations (MYH7, p.A26V and MYBPC3, p.R160W) were revealed to be associated with DCM. The mutations were most frequently found in the sarcomere (MYH6, MYBPC3, MYH7, TNNC1, TNNT2 and MYL3) and cytoskeletal (MYPN, DES and VCL) genes. As genetic testing is a useful tool in the clinical management of disease, testing for pathogenic mutations is beneficial to the treatment of patients with DCM and may assist in predicting disease risk for their family members before the onset of symptoms.


Asunto(s)
Cardiomiopatía Dilatada/genética , Predisposición Genética a la Enfermedad/genética , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Mutación , Adulto , Anciano , Análisis de Varianza , Cardiomiopatía Dilatada/diagnóstico , Cardiomiopatía Dilatada/fisiopatología , Electrocardiografía , Femenino , Pruebas Genéticas/métodos , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Fenotipo , Reproducibilidad de los Resultados , Sensibilidad y Especificidad
20.
Yi Chuan ; 37(7): 635-44, 2015 07.
Artículo en Chino | MEDLINE | ID: mdl-26351163

RESUMEN

Inherited cardiomyopathy is the most common hereditary cardiac disease. It also causes a significant proportion of sudden cardiac deaths in young adults and athletes. So far, approximately one hundred genes have been reported to be involved in cardiomyopathies through different mechanisms. Therefore, the identification of the genetic basis and disease mechanisms of cardiomyopathies are important for establishing a clinical diagnosis and genetic testing. Next-generation semiconductor sequencing (NGSS) technology platform is a high-throughput sequencer capable of analyzing clinically derived genomes with high productivity, sensitivity and specificity. It was launched in 2010 by Life Technologies of USA, and it is based on a high density semiconductor chip, which was covered with tens of thousands of wells. NGSS has been successfully used in candidate gene mutation screening to identify hereditary disease. In this review, we summarize these genetic variations, challenge and application of NGSS in inherited cardiomyopathy, and its value in disease diagnosis, prevention and treatment.


Asunto(s)
Cardiomiopatías/genética , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Cardiomiopatías/diagnóstico , Pruebas Genéticas , Humanos
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