RESUMO
A great deal of attention has been focused on the secondary metabolites produced by marine endophytic fungi, which can be better alternatives to chemicals, such as biopesticides, for control of polyphagous pests. On the basis of its novel biocontrol attributes, chemical investigation of a marine alga-derived endophytic fungus, Acremonium vitellinum, resulted in the isolation of three chloramphenicol derivatives (compounds 1â»3). Their chemical structures were elucidated by detailed analysis of their nuclear magnetic resonance spectra, high-resolution electrospray ionization mass spectrometry, and by comparison with the data available in the literature. In this paper, compound 2 was firstly reported as the natural origin of these fungal secondary metabolites. The insecticidal activities of compounds 1â»3 against the cotton bollworm, Helicoverpa armigera, were evaluated. The natural compound 2 presented considerable activity against H. armigera, with an LC50 value of 0.56 ± 0.03 mg/mL (compared to matrine with an LC50 value of 0.24 ± 0.01 mg/mL). Transcriptome sequencing was used to evaluate the molecular mechanism of the insecticidal activities. The results presented in this study should be useful for developing compound 2 as a novel, ecofriendly and safe biopesticide.
Assuntos
Acremonium/fisiologia , Cloranfenicol/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Inseticidas/farmacologia , Larva/crescimento & desenvolvimento , Lepidópteros/crescimento & desenvolvimento , Controle Biológico de Vetores , Animais , Cloranfenicol/química , Cloranfenicol/isolamento & purificação , Proteínas de Insetos/genética , Inseticidas/química , Inseticidas/isolamento & purificação , Larva/efeitos dos fármacos , Larva/genética , Lepidópteros/efeitos dos fármacos , Lepidópteros/genéticaRESUMO
Considerable attention has been paid to marine derived endophytic fungi, owing to their capacity to produce novel secondary metabolites with potent bioactivities. In this study, two new compounds with a prenylated diphenyl ether structure-diorcinol L (1) and (R)-diorcinol B (2)-were isolated from the marine algal-derived endophytic fungus Aspergillus tennesseensis, along with seven known compounds: (S)-diorcinol B (3), 9-acetyldiorcinol B (4), diorcinol C (5), diorcinol D (6), diorcinol E (7), diorcinol J (8), and a dihydrobenzofuran derivative 9. Their structures were elucidated by extensive NMR spectroscopy studies. Compound 2 represents the first example of an R-configuration in the prenylated moiety. All these isolated compounds were examined for antimicrobial and cytotoxic activities. Compounds 1â»9 exhibited antimicrobial activities against some human- and plant-pathogenic microbes with MIC values ranging from 2 to 64 µg/mL. Moreover, compound 9 displayed considerable inhibitory activity against the THP-1 cell line in vitro, with an IC50 value of 7.0 µg/mL.
Assuntos
Organismos Aquáticos/microbiologia , Aspergillus/química , Endófitos/química , Éteres Fenílicos/isolamento & purificação , Prenilação , Bactérias/efeitos dos fármacos , Espectroscopia de Ressonância Magnética Nuclear de Carbono-13 , Linhagem Celular Tumoral , Humanos , Testes de Sensibilidade Microbiana , Éteres Fenílicos/química , Espectroscopia de Prótons por Ressonância MagnéticaRESUMO
OBJECTIVE: To study the expression and significance of the mammalian target of rapamycin (mTOR)/eukaryote initiating factor 4E binding protein 1(4EBP1)/hypoxia inducible factor-1α (HIF-1α)/vascular endothelial growth factor (VEGF) signaling pathway in asthmatic mice. METHODS: Forty SPF level 6-8 week-old female Balb/C mice were randomly divided into control, asthma, budesonide and mTOR inhibitor (rapamycin) intervention groups (n=10 each). The asthmatic mouse model was prepared via OVA induction and challenge test. The intervention groups were administered with rapamycin at the dosage of 3â mg/kg by an intraperitoneal injection or budesonide suspension at the dosage of l mg by aerosol inhalation respectively 30 minutes before the OVA challenge. The control and asthma groups were treated with normal saline instead. The concentrations of HIF-1α and VEGF in bronchoalveolar lavage fluid (BALF) were examined using ELISA 24 hours after the last challenge. The pathological changes of lung tissue were observed by hematoxylin-eosin (HE) staining. The p-mTOR and p-4EBP1 from the lung tissues were detected by immunohistochemistry and Western blot. Pearson analysis was used to study the correlation between p-mTOR, p-4EBP1, HIF-1α, and VEGF expression. RESULTS: Compared with the control group, inflammatory cell infiltration and secretions in the trachea increased in the asthma group. The levels of HIF-1α and VEGF in BALF and p-mTOR and p-4EBP1 expression in lung tissues also increased (P<0.01). Compared with the asthma group, inflammatory cell infiltration and secretions in the trachea were reduced in the two intervention groups, and the levels of HIF-1α and VEGF in BALF and p-mTOR and p-4EBP1 expression in lung tissues were also reduced (P<0.01). There were no significant differences in the above changes between the two intervention groups and control group (P>0.05). In the asthma group, there was a pairwise positive correlation between lung p-mTOR and p-4EBP1 expression and HIF-1α and VEGF levels in BALF (P<0.05). However, there were no correlations in the above indexes in the intervention groups and control group. CONCLUSIONS: p-mTOR, p-4EBP1, HIF-1α and VEGF together are involved in the pathogenesis of asthma. Rapamycin treatment can block this signaling pathway, suggesting that this pathway can be used as a novel target for asthma treatment.
Assuntos
Asma/metabolismo , Proteínas de Transporte/fisiologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/fisiologia , Pulmão/química , Fosfoproteínas/fisiologia , Transdução de Sinais/fisiologia , Serina-Treonina Quinases TOR/fisiologia , Fator A de Crescimento do Endotélio Vascular/fisiologia , Proteínas Adaptadoras de Transdução de Sinal , Animais , Asma/tratamento farmacológico , Proteínas de Transporte/análise , Proteínas de Ciclo Celular , Fatores de Iniciação em Eucariotos , Feminino , Subunidade alfa do Fator 1 Induzível por Hipóxia/análise , Pulmão/patologia , Camundongos , Camundongos Endogâmicos BALB C , Fosfoproteínas/análise , Serina-Treonina Quinases TOR/análise , Fator A de Crescimento do Endotélio Vascular/análiseRESUMO
White spot syndrome virus (WSSV) is the main pathogen of shrimp culture, and has brought great losses of the shrimp aquaculture industry every year since it has been found. However, the specific mechanism of the virus into the cell is not very clear. Recent research suggests that clathrin-mediated endocytosis is involved in WSSV infection. By sequence analysis, clathrin coat AP17 is an σ subunit of AP-2 complex which is involved in clathrin-mediated endocytosis. To obtain the full-length sequence of Clathrin coat AP17 of Litopenaeus vannamei (LvCCAP17), the rapid amplification of cDNA ends (RACE) was performed to get the sequence of 3'and 5' end and splicing by DNAMAN. The full-length sequence of LvCCAP17 is 842 bp and expected to encoding 142 amino acids, and the amino acid sequence was analyzed by online software. The mRNA expression of LvCCAP17 in different tissues was carried out with quantitative real-time PCR and the LvCCAP17 was detected in all tested tissues of Litopenaeus vannamei. The transcriptional expression level of LvCCAP17 in epithelium and hepatopancreas was significantly up-regulated after WSSV infection. Far-Western blotting and ELISA assay showed that LvCCAP17 interacted with rVP26 and rVP37. Silencing of LvCCAP17 gene by double-strand RNA (dsRNA) interference significantly delay of cumulative mortality rate in WSSV infected shrimp and reduced the expression level of immediate early gene 1(ie1) and vp28. These results indicated that clathrin-meated endocytosis is responsible for WSSV infection.
Assuntos
Proteínas de Artrópodes/genética , Clatrina/genética , Penaeidae/genética , Penaeidae/imunologia , Vírus da Síndrome da Mancha Branca 1/fisiologia , Sequência de Aminoácidos , Animais , Proteínas de Artrópodes/química , Proteínas de Artrópodes/metabolismo , Sequência de Bases , Clatrina/química , Clatrina/metabolismo , Penaeidae/virologia , Filogenia , Interferência de RNA , RNA de Cadeia Dupla/genética , RNA de Cadeia Dupla/metabolismo , Alinhamento de SequênciaRESUMO
OBJECTIVE: To investigate the changes and clinical significance of lymphocyte subsets in infants with bronchitis, bronchopneumonia, and bronchiolitis. METHODS: A total of 111 children with bronchitis, 418 children with bronchopneumonia, and 83 children with bronchiolitis were enrolled as disease groups, and 235 healthy children were enrolled as control group. Flow cytometry was applied to measure lymphocyte subsets. RESULTS: The bronchitis group had significantly lower numbers of T cells and CD3+CD8+ T cells than the control group (P<0.05). The bronchopneumonia group had significantly lower numbers of T cells and CD3+CD8+ T cells, a significantly higher number of T helper (Th) cells, and a significantly higher CD4/CD8 ratio than the control group, as well as a significantly higher number of Th cells than the bronchitis group. Compared with the children with mild bronchopneumonia, those with severe bronchopneumonia showed a reduction in T cells and an increase in B cells (P<0.05). The bronchiolitis group had a significantly higher number of Th cells, a significantly higher CD4/CD8 ratio, and a significantly lower number of CD3+CD8+ T cells than the control group (P<0.01). The disease groups showed a significantly higher number of B cells and a significantly lower number of natural killer cells than the control group (P<0.05). CONCLUSIONS: A low, disturbed cellular immune function and a high humoral immune function are involved in the development and progression of lower respiratory tract infectious diseases. The changes in immune function are related to the type and severity of diseases.
Assuntos
Subpopulações de Linfócitos/imunologia , Infecções Respiratórias/imunologia , Bronquiolite/imunologia , Bronquite/imunologia , Broncopneumonia/imunologia , Relação CD4-CD8 , Pré-Escolar , Feminino , Humanos , Lactente , Células Matadoras Naturais/imunologia , MasculinoRESUMO
The interaction between viral structural proteins and host plays key functions in viral infection. In previous studies, most research have been undertaken to explore the interaction of envelope structural proteins with host molecules. However, how the nucleocapsid proteins of WSSV interacted with host molecules remained largely unknown. In this study, the interaction of nucleocapsid protein VP51 and ribosomal protein L7 of Litopenaeus vannamei (LvRPL7) was reported. Furthermore, the mRNA transcriptional response of LvRPL7 to WSSV was investigated. The results showed that LvRPL7 was widely distributed in all analyzed tissues of L. vannamei. The high expression levels of LvRPL7 were found in the tissues of muscle and gills. The temporal expression of LvRPL7 in WSSV-challenged shrimp showed that LvRPL7 was up-regulated (P < 0.5) in the muscle at 8 h and 24 h post WSSV challenge and then restored to the normal levels. But the LvRPL7 expression was up-regulated (P < 0.5) in the hepatopancreas at 8 h post WSSV challenge and down-regulated at 12 h and 24 h post WSSV challenge. Indirect immunofluorescence assay indicated that LvRPL7 was mainly located on the surface and cytoplasm of hemocytes. Far-Western blotting showed that VP51 bound with LvRPL7. Moreover, ELISA results appeared that LvRPL7 interacted with VP51 in concentration dependent manner. Neutralization assay in vivo showed that anti-LvRPL7 antibody significantly delayed WSSV infection. Our results reveal that LvRPL7 was involved in WSSV infection.
Assuntos
Proteínas de Artrópodes/metabolismo , Proteínas do Nucleocapsídeo/metabolismo , Penaeidae/virologia , Proteínas Ribossômicas/metabolismo , Vírus da Síndrome da Mancha Branca 1/fisiologia , Animais , Proteínas de Artrópodes/genética , Interações Hospedeiro-Patógeno , Penaeidae/metabolismo , RNA Mensageiro/metabolismo , Proteínas Ribossômicas/genéticaRESUMO
OBJECTIVES: Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease that affects the quality of life (QoL) of patients. This study aimed to evaluate the differences in perceptions of PBC among physicians from different hospital departments and patients with PBC. METHODS: An online survey regarding the general knowledge, diagnosis, and management of PBC was completed by physicians and patients. RESULTS: A total of 239 patients with PBC and 239 physicians from eight hospital departments (gastroenterology, infectious diseases, rheumatology, hepatobiliary surgery, pathology, clinical laboratory, ultrasound, and radiology) completed the survey. The results showed that physicians from departments other than gastroenterologists and rheumatologists lacked knowledge of PBC, and that junior gastroenterologists were uncertain about the diagnostic and treatment pathways of PBC. Importantly, the lack of knowledge significantly impacted the QoL of patients, especially the emotional scores of PBC-40 (odds ratio -2.556, 95% confidence interval -3.852 to -1.260, P < 0.001). In addition, there was a perceived knowledge gap between patients and gastroenterologists. CONCLUSIONS: Physicians must improve their awareness of PBC. Patient education and patient-physician communication are important for improving the patient's QoL.
Assuntos
Doenças Autoimunes , Colangite , Gastroenterologistas , Cirrose Hepática Biliar , Humanos , Cirrose Hepática Biliar/diagnóstico , Qualidade de Vida , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: To study changes to CD4(+)CD25(high+)CD127(low) regulatory T cells (Treg) in peripheral blood from children with bronchiolitis, and to explore its clinical significance. METHODS: Thirty-one children with bronchiolitis and aged under two years were randomly enrolled as the bronchiolitis group, and 25 under two-year-olds with bronchopneumonia were randomly enrolled as the bronchopneumonia group. A further twenty-five children with non-infectious diseases such as hernia and renal calculus served as the control group. The level of CD4(+)CD25(high+)CD127(low) Treg in peripheral blood was measured by multi-color detection and multi-parameter flow cytometry. RESULTS: The proportion of CD4(+)CD25(high+)CD127(low) Treg in peripheral blood in the bronchiolitis group (8.0%±2.1%) was significantly lower than in the bronchopneumonia (9.6%±2.6%; P<0.05) and control groups (11.3%±2.9%; P<0.05). CONCLUSIONS: CD4(+)CD25(high+)CD127(low) Treg level in peripheral blood may be an index of immunological function in infants. A decreased level of CD4(+)CD25(high+)CD127(low) Treg in peripheral blood suggests that Treg cells may be involved in the pathogenesis and development of bronchiolitis.
Assuntos
Subunidade alfa de Receptor de Interleucina-2/sangue , Subunidade alfa de Receptor de Interleucina-7/sangue , Linfócitos T Reguladores/imunologia , Bronquiolite/imunologia , Pré-Escolar , Feminino , Citometria de Fluxo , Humanos , Lactente , MasculinoRESUMO
OBJECTIVE: To study myeloid-derived suppressor cells (MDSC) levels in peripheral blood of infants with recurrent wheezing, and the role of MDSC in the development of recurrent wheezing. METHODS: Thirty-one infants with recurrent wheezing at wheezing attacks were randomly enrolled in the study. Twenty-seven infants with bronchopneumonia and 27 preoperative infants (hernia or renal calculus), without infectious or neoplastic diseases, were selected as controls. The proportion of MDSC in peripheral blood mononuclear cells (PBMC) was measured by flow cytometry. RESULTS: The proportion of MDSC in PBMC in infants with wheezing was significantly higher than in those with bronchopneumonia and preoperative infants (P<0.05). CONCLUSIONS: MDSC levels increase in infants with recurrent wheezing, suggesting that MDSC may play a crucial role in the development of this disorder.
Assuntos
Leucócitos Mononucleares/imunologia , Células Mieloides/imunologia , Sons Respiratórios/imunologia , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , RecidivaRESUMO
AIM: To determine whether an antisense RNA corresponding to the human Alu transposable element (Aluas RNA) can protect human lens epithelial cells (HLECs) from methylglyoxal-induced apoptosis. METHODS: Cell counting kit-8 (CCK-8) and 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays were used to assess HLEC viability. HLEC viability/death was detected using a Calcein-AM/PI double staining kit; the annexin V-FITC method was used to detect HLEC apoptosis. The cytosolic reactive oxygen species (ROS) levels in HLECs were determined using a reactive species assay kit. The levels of malondialdehyde (MDA) and the antioxidant activities of total-superoxide dismutase (T-SOD) and glutathione peroxidase (GSH-Px) were assessed in HLECs using their respective kits. RT-qPCR and Western blotting were used to measure mRNA and protein expression levels of the genes. RESULTS: Aluas RNA rescued methylglyoxal-induced apoptosis in HLECs and ameliorated both the methylglyoxal-induced decrease in Bcl-2 mRNA and the methylglyoxal-induced increase in Bax mRNA. In addition, Aluas RNA inhibited the methylglyoxal-induced increase in Alu sense RNA expression. Aluas RNA inhibited the production of ROS induced by methylglyoxal, restored T-SOD and GSH-Px activity, and moderated the increase in MDA content after treatment with methylglyoxal. Aluas RNA significantly restored the methylglyoxal-induced down-regulation of Nrf2 gene and antioxidant defense genes, including glutathione peroxidase, heme oxygenase 1, γ-glutamylcysteine synthetase and quinone oxidoreductase 1. Aluas RNA ameliorated methylglyoxal-induced increases of the mRNA and protein expression of Keap1 that is the negative regulator of Nrf2. CONCLUSION: Aluas RNA reduces apoptosis induced by methylglyoxal by enhancing antioxidant defense.
RESUMO
OBJECTIVE: To investigate whether human short interspersed nuclear element antisense RNA (Alu antisense RNA; Alu asRNA) could delay human fibroblast senescence and explore the underlying mechanisms. METHODS: We transfected Alu asRNA into senescent human fibroblasts and used cell counting kit-8 (CCK-8), reactive oxygen species (ROS), and senescence-associated beta-galactosidase (SA-ß-gal) staining methods to analyze the anti-aging effects of Alu asRNA on the fibroblasts. We also used an RNA-sequencing (RNA-seq) method to investigate the Alu asRNA-specific mechanisms of anti-aging. We examined the effects of KIF15 on the anti-aging role induced by Alu asRNA. We also investigated the mechanisms underlying a KIF15-induced proliferation of senescent human fibroblasts. RESULTS: The CCK-8, ROS and SA-ß-gal results showed that Alu asRNA could delay fibroblast aging. RNA-seq showed 183 differentially expressed genes (DEGs) in Alu asRNA transfected fibroblasts compared with fibroblasts transfected with the calcium phosphate transfection (CPT) reagent. The KEGG analysis showed that the cell cycle pathway was significantly enriched in the DEGs in fibroblasts transfected with Alu asRNA compared with fibroblasts transfected with the CPT reagent. Notably, Alu asRNA promoted the KIF15 expression and activated the MEK-ERK signaling pathway. CONCLUSION: Our results suggest that Alu asRNA could promote senescent fibroblast proliferation via activation of the KIF15-mediated MEK-ERK signaling pathway.
Assuntos
Sistema de Sinalização das MAP Quinases , RNA Antissenso , Humanos , Sistema de Sinalização das MAP Quinases/fisiologia , Espécies Reativas de Oxigênio/metabolismo , RNA Antissenso/metabolismo , RNA Antissenso/farmacologia , Senescência Celular , Envelhecimento , Quinases de Proteína Quinase Ativadas por Mitógeno , Fibroblastos , Cinesinas/metabolismo , Cinesinas/farmacologiaRESUMO
BACKGROUND/AIMS: The examination of HCV virological clearance through several randomized clinical trials of telaprevir in genotype 1 chronic hepatitis C. METHODOLOGY: We analyzed the effect of telaprevir on the end of treatment virological response and the sustained response, and investigated its harmful effect using meta-analysis of 5 randomized controlled trials. RESULTS: Overall analysis revealed a significant effect of telaprevir in both naive patients (RR, 1.32; 95% CI, 1.08-1.60) and previously failed treated patients (p<0.0001). Monotherapy and double therapy seemed to show no effect in naive patients. Triple therapy followed with PegIFN-2a plus ribavirin seemed to be effective in both naive patients and previously failed treated patients. Telaprevir was associated with a significantly higher incidence of serious adverse events (RR, 1.45; 95% CI, 1.00-2.10) and with discontinuation (RR, 2.23; 95% CI, 1.40-3.55) because of adverse events. In naive patients, relapsers and non-responders, the regimen of telaprevir/ PegIFN-2a/ribavirin for 12 weeks followed by PegIFN-2a/ribavirin for 12 weeks (T12PR24) was the optimal regimen regarding to efficiency and duration. CONCLUSIONS: Telaprevir combined with PegIFN-2a plus ribavirin may improve sustained response in genotype 1 chronic hepatitis C. Regimen T12PR24 may be the best regimen in this respect. New randomized controlled trials are required to confirm this meta-analysis.
Assuntos
Antivirais/uso terapêutico , Hepacivirus/genética , Hepatite C Crônica/dietoterapia , Oligopeptídeos/uso terapêutico , Antivirais/efeitos adversos , Quimioterapia Combinada , Genótipo , Hepatite C Crônica/diagnóstico , Hepatite C Crônica/virologia , Humanos , Interferon-alfa/uso terapêutico , Oligopeptídeos/efeitos adversos , Polietilenoglicóis/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Proteínas Recombinantes/uso terapêutico , Ribavirina/uso terapêutico , Fatores de Tempo , Resultado do TratamentoRESUMO
SV40 PolyA (Simian virus 40 PolyA, also called PolyA) sequence is DNA sequence (240 bp) that possesses the activity of transcription termination and can add PolyA tail to mRNA. PolyA contains AATAAA hexanucleotide polyadenylation signal. Fourteen copies of Alu in sense orientation (Alu14) were inserted downstream of GFP in pEGFP-C1 to construct pAlu14 plasmid, and then HeLa cells were transiently transfected with pAlu14. Northern blot and fluorescence microscope were used to observe GFP RNA and protein expressions. Our results found that Alu tandem sequence inhibited remarkably GFP gene expression, but produced higher-molecular-mass GFP fusion RNA. PolyA and its sequence that was deleted AATAAA signal in sense or antisense orientation were inserted between GFP and Alu tandem sequence in pAlu14. The results showed that all the inserted PolyA sequences partly eliminated the inhibition induced by Alu14. PolyA sequences without AATAAA signal in sense or antisense orientation still induced transcription termination. Antisense PolyA (PolyAas) was divided into four fragments that all are 60 bp long and the middle two fragments were named 2F2R and 3F3R. 2F2R or 3F3R was inserted upstream of Alu tandem sequence in pAlu14. The molecular mass of GFP fusion RNA increased when the copy number of 2F2R increased. 2F2R can support transcription elongation when 2F2R is located upstream of other 2F2R. Nevertheless, 2F2R located upstream of Alu tandem sequence can induce transcription termination. Inserting one copy or 64 copies of 3F3R in upstream of Alu tandem sequence caused the production of lower-molecular-mass GFP RNA.
Assuntos
Expressão Gênica , Proteínas de Fluorescência Verde/genética , Poli A/metabolismo , Vírus 40 dos Símios/genética , Transcrição Gênica , Elementos Alu , Códon de Terminação , Proteínas de Fluorescência Verde/metabolismo , Células HeLa , Humanos , Poli A/genética , Vírus 40 dos Símios/metabolismo , TransfecçãoRESUMO
BACKGROUND: Little is known about the renoprotective effects of statins on the regulation of urinary oxidative stress markers and proteinuria in patients with diabetic nephropathy. Therefore, we conducted this protocol of systematic review and meta-analysis to evaluate the role of statins in patients with early diabetic nephropathy. METHODS: We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols reporting guidelines to conduct this study. The electronic databases EMBASE, PUBMED, CINAHL, and Web of Science will be searched from the earliest available time to July 2022. The population is defined as participants with early diabetic nephropathy. The Intervention groups are given any one of the statins, such as simvastatin or rosuvastatin. The control groups are treated with angiotensin-converting enzyme inhibitor or placebo alone. The primary outcome is estimated glomerular filtration rate; secondary outcome is serological indicators including triglyceride, cholesterol, C-reactive protein, and complications. The Jadad scale will be used to assess the methodological quality of each study included in this meta-analysis. RESULT CONCLUSION: We hypothesized that statins would have a positive renoprotective effect in such patients. OSF REGISTRATION NUMBER: 10.17605/OSF.IO/ESMWR.
Assuntos
Diabetes Mellitus , Nefropatias Diabéticas , Inibidores de Hidroximetilglutaril-CoA Redutases , Diabetes Mellitus/tratamento farmacológico , Nefropatias Diabéticas/tratamento farmacológico , Taxa de Filtração Glomerular , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Metanálise como Assunto , Revisões Sistemáticas como AssuntoRESUMO
BACKGROUND: Fatty liver is a common chronic liver disease worldwide. It is associated with an increasing morbidity in China in recent years. The aim of this study was to analyze the effect of drinking alcohol on the hemoglobin and biochemical values of patients with fatty liver. METHODS: We investigated the clinical and laboratory data of 669 patients with fatty liver. Of the 669 patients, 166 consumed alcohol more than 60 g per week for at least 2 years, and 503 did not have a history of long-term alcohol consumption. We further analyzed the relationship between alcohol consumption and clinical characteristics of these patients. RESULTS: The values of aspartate transaminase (AST), gamma-glutamyl transpeptidase (GGT), and hemoglobin in the long-term consumption group were significantly higher than those in the non long-term consumption group (P<0.05). In the patients without long-term alcohol consumption, the values of GGT and hemoglobin in patients with light alcohol consumption were significantly higher than those in non alcohol consumers (P<0.05). CONCLUSION: Alcohol consumption is associated with significantly increased values of AST, GGT, and hemoglobin in patients with fatty liver, suggesting their potential roles in hepatic steatosis.
Assuntos
Consumo de Bebidas Alcoólicas/efeitos adversos , Aspartato Aminotransferases/sangue , Ensaios Enzimáticos Clínicos , Fígado Gorduroso Alcoólico/diagnóstico , Fígado Gorduroso/diagnóstico , Hemoglobinas/metabolismo , gama-Glutamiltransferase/sangue , Adulto , Idoso , Biomarcadores/sangue , Distribuição de Qui-Quadrado , China , Fígado Gorduroso/sangue , Fígado Gorduroso Alcoólico/sangue , Fígado Gorduroso Alcoólico/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica , Valor Preditivo dos Testes , Prognóstico , Medição de Risco , Fatores de Risco , Fatores de Tempo , Regulação para CimaRESUMO
OBJECTIVE: To study the expression of serum Clara cell secretory protein 10 (CC10) and total IgE concentration in wheezing children under 5 years old. METHODS: Fifty-nine children with recurrent wheezing under 5 years old were classified into two groups: wheezing group 1 with atopic high risks (n=33) and wheezing group 2 without atopic high risks (n=26). Twenty-three children without infectious diseases served as a control group. Serum levels of CC10 and IgE were measured using a solid-phase sandwich ELISA. RESULTS: The serum levels of CC10 in wheezing group 1 (3.95 ± 1.26 ng/mL) and wheezing group 2 (5.41 ± 1.64 ng/mL) were significantly lower than those in the control group (8.72 ± 2.23 ng/mL; P<0.01). The wheezing group 1 showed more decreased serum levels of CC10 compared with wheezing group 2 (P<0.05). The serum IgE levels in wheezing group 1 were significantly higher than those in wheezing group 2 and the control group (P<0.05). There were no significant differences in serum IgE levels between the wheezing group 2 and control group. There was a negative correlation between serum levels of CC10 and IgE in wheezing group 1 (r=-0.912, P < 0.01). CONCLUSIONS: Serum CC10 levels decrease remarkably in wheezing children, and more significant decrease is noted in patients with atopic high risks. Serum CC10 levels are negatively correlated to serum IgE levels in patients with atopic high risks.
Assuntos
Sons Respiratórios/imunologia , Uteroglobina/sangue , Pré-Escolar , Feminino , Humanos , Imunoglobulina E/sangue , Lactente , MasculinoRESUMO
AIM: to study the molecular mechanisms underlying α-tocopheryl succinate (α-TOS)-induced apoptosis in erbB2-positive breast cancer cells and to determine whether α-TOS and the human recombinant TNF-related apoptosis-inducing ligand (hrTRAIL) act synergically to induce cell death of erbB2-expressing breast cancer cells. METHODS: the annexin V binding method was used to measure apoptosis induced by α-TOS and/or hrTRAIL. RT-PCR and Western blotting were performed to detect gene and protein expression. A colorimetric assay was performed to detect caspase activity. The TransAM(TM) NF-κB p65 kit was used to assess NF-κB activation. RESULTS: α-TOS (100 µmol/L) significantly inhibited NF-κB nuclear translocation in erbB2-expressing breast cancer cells; this inhibition is expected to result in the inactivation of NF-κB. α-TOS (50 and 100 µmol/L) inhibited the expression of Flice-like inhibitory protein (FLIP) and cellular inhibitor of apoptosis protein 1 (c-IAP1) in erbB2-positive cells. α-TOS (100 µmol/L) inhibited Akt activation and augmented the activity of caspase 3 and caspase 8 in breast cancer cells expressing erbB2. α-TOS (50 µmol/L) and hrTRAIL (30 mg/mL) acted synergically to induce apoptosis in breast cancer cells. α-TOS also decreased the hrTRAIL-induced transient activation of NF-κB . CONCLUSION: our results suggest that α-TOS mediates the apoptosis of erbB2-positive breast cancer cells and acts synergically with hrTRAIL via the NF-κB pathway.
Assuntos
Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , NF-kappa B/fisiologia , Receptor ErbB-2/metabolismo , alfa-Tocoferol/farmacologia , Neoplasias da Mama , Caspases/genética , Caspases/metabolismo , Linhagem Celular Tumoral , Feminino , Humanos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Ligante Indutor de Apoptose Relacionado a TNF/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
OBJECTIVE: To study the value of eosinophils (EOS) and interleukin-17 (IL-17) in nasopharyngeal secretions in the evaluation of progress of wheezing in children under 5 years old. METHODS: Fifty-three children under five years old who had recurrent wheezing were classified into two groups: wheezing group I with atopic body (n=27) and wheezing group II without atopic body (n=26). Twenty pre-surgical children with non-infectious disease were used as the control group. Nasopharyngeal secretions were collected. Inflammatory cells in nasopharyngeal secretions were counted under the microscope. IL-17 levels in supernatants were measured using ELISA. RESULTS: EOS counts in nasopharyngeal secretions in wheezing group I were significantly higher than those in wheezing group II and the control group (p<0.05, p<0.01, respectively). There were no significant differences in EOS counts between wheezing II and the control groups. The IL-17 levels in both wheezing groups were significantly higher than those in the control group (p<0.01), and the wheezing group I had increased IL-17 levels than wheezing group II (1 474+/-974 pg/mL vs 788+/-132 pg/mL; p<0.05). The IL-17 level was positively correlated with the EOS counts in wheezing group I (r=0.62, p<0.05). CONCLUSIONS: EOS counts and IL-17 levels in nasopharyngeal secretions may be used as indices for identifying the tendency to develop asthma in children under 5 years old with wheezing.
Assuntos
Eosinófilos/fisiologia , Interleucina-17/análise , Nasofaringe/metabolismo , Sons Respiratórios/imunologia , Pré-Escolar , Feminino , Humanos , Lactente , Contagem de Leucócitos , MasculinoRESUMO
Endophytic fungi have proven to be prolific producers of bioactive secondary metabolites with agricultural applications. In this study, bioassay-guided isolation of the endophytic fungus Acremonium vitellinum yielded four anthraquinone derivatives (compounds 1-4), including a previously undescribed dimethylated derivative of bipolarin, 6,8-di-O-methylbipolarin (1). Their structures were determined by 1D and 2D nuclear magnetic resonance analysis as well as high-resolution electrospray ionization mass spectrometry data, and the absolute configuration of 1 was established by comparing the calculated and experimental electronic circular dichroism spectra. The insecticidal activity of the isolated compounds against the cotton bollworm Helicoverpa armigera was evaluated. The new compound 1 showed the strongest larvicidal activity against the 3rd instar larvae of H. armigera with an LC50 value of 0.72 mg/mL. In addition, transcriptome sequencing was performed to evaluate the molecular mechanism of the insecticidal activity. In total, 5732 differentially expressed genes were found, among which 2904 downregulated genes and 2828 upregulated genes were mainly involved in cell autophagy, apoptosis, and DNA mismatch repair and replication. The results presented in this study reveal how 1 exerts its insecticidal effects against H. armigera via genome-wide differential gene expression analyses. Our findings suggest that anthraquinone derivatives are potential biopesticides for cotton bollworm control.
Assuntos
Acremonium/química , Antraquinonas/química , Antraquinonas/farmacologia , Inseticidas/química , Inseticidas/farmacologia , Animais , Antraquinonas/isolamento & purificação , Endófitos/química , Proteínas de Insetos/genética , Inseticidas/isolamento & purificação , Larva/efeitos dos fármacos , Larva/genética , Mariposas/efeitos dos fármacos , Mariposas/genética , Mariposas/crescimento & desenvolvimentoRESUMO
The Yunnan province has one of the most serious outbreaks of the plague epidemic in China. Small mammals and fleas are risk factors for the occurrence of plague in commensal plague foci. Understanding the relationship between fleas and small mammals will help control fleas and prevent the onset of the plague. Four hundred and twenty-one small mammals, belonging to 9 species, were captured. Of these, 170 small mammals (40.4%) were found infested with fleas. A total of 992 parasitic fleas (including 5 species) were collected. The number of Leptopsylla segnis and Xenopsylla cheopis accounted for 91.03% (903/992). The final multiple hurdle negative binomial regression model showed that when compared with Rattus tanezumi, the probability of flea infestation with Mus musculus as well as other host species decreased by 58% and 99%, respectively, while the number of flea infestations of the other host species increased by 4.71 folds. The probability of flea prevalence in adult hosts increased by 74%, while the number of fleas decreased by 76%. The number of flea infestations in small male mammals increased by 62%. The number of fleas in small mammals weighing more than 59 g has been multiplied by about 4. R. tanezumi is the predominant species in households in the west Yunnan province, while L.segnis and X. cheopis were dominant parasitic fleas. There is a strong relationship between the abundance of fleas and the characteristics of small mammals (e.g. Species, age, sex, and body weight).