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1.
Immunity ; 57(6): 1306-1323.e8, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38815582

RESUMO

Group 3 innate lymphoid cells (ILC3s) regulate inflammation and tissue repair at mucosal sites, but whether these functions pertain to other tissues-like the kidneys-remains unclear. Here, we observed that renal fibrosis in humans was associated with increased ILC3s in the kidneys and blood. In mice, we showed that CXCR6+ ILC3s rapidly migrated from the intestinal mucosa and accumulated in the kidney via CXCL16 released from the injured tubules. Within the fibrotic kidney, ILC3s increased the expression of programmed cell death-1 (PD-1) and subsequent IL-17A production to directly activate myofibroblasts and fibrotic niche formation. ILC3 expression of PD-1 inhibited IL-23R endocytosis and consequently amplified the JAK2/STAT3/RORγt/IL-17A pathway that was essential for the pro-fibrogenic effect of ILC3s. Thus, we reveal a hitherto unrecognized migration pathway of ILC3s from the intestine to the kidney and the PD-1-dependent function of ILC3s in promoting renal fibrosis.


Assuntos
Movimento Celular , Fibrose , Rim , Linfócitos , Receptor de Morte Celular Programada 1 , Receptores CXCR6 , Receptores de Interleucina , Transdução de Sinais , Animais , Fibrose/imunologia , Camundongos , Receptores CXCR6/metabolismo , Receptores CXCR6/imunologia , Receptor de Morte Celular Programada 1/metabolismo , Transdução de Sinais/imunologia , Movimento Celular/imunologia , Humanos , Rim/patologia , Rim/imunologia , Rim/metabolismo , Linfócitos/imunologia , Linfócitos/metabolismo , Receptores de Interleucina/metabolismo , Receptores de Interleucina/imunologia , Camundongos Endogâmicos C57BL , Nefropatias/imunologia , Nefropatias/metabolismo , Nefropatias/patologia , Imunidade Inata/imunologia , Camundongos Knockout , Mucosa Intestinal/imunologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Intestinos/imunologia , Intestinos/patologia
2.
Nat Immunol ; 19(7): 755-765, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29915298

RESUMO

The cytokines IL-17A and IL-17F have 50% amino-acid identity and bind the same receptor; however, their functional differences have remained obscure. Here we found that Il17f-/- mice resisted chemically induced colitis, but Il17a-/- mice did not, and that Il17f-/- CD45RBhiCD4+ T cells induced milder colitis in lymphocyte-deficient Rag2-/- mice, accompanied by an increase in intestinal regulatory T cells (Treg cells). Clostridium cluster XIVa in colonic microbiota capable of inducing Treg cells was increased in both Il17f-/- mice and mice given transfer Il17f-/- T cells, due to decreased expression of a group of antimicrobial proteins. There was substantial production of IL-17F, but not of IL-17A, not only by naive T cells but also by various colon-resident cells under physiological conditions. Furthermore, antibody to IL-17F suppressed the development of colitis, but antibody to IL-17A did not. These observations suggest that IL-17F is an effective target for the treatment of colitis.


Assuntos
Colite/imunologia , Microbioma Gastrointestinal , Interleucina-17/antagonistas & inibidores , Linfócitos T Reguladores/imunologia , Animais , Células Cultivadas , Clostridium/crescimento & desenvolvimento , Clostridium/isolamento & purificação , Colite/tratamento farmacológico , Interleucina-17/genética , Interleucina-17/fisiologia , Intestinos/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fosfolipases A2/biossíntese , Fosfolipases A2/genética , Prevotella/isolamento & purificação , Ribonuclease Pancreático/biossíntese , Ribonuclease Pancreático/genética , beta-Defensinas/biossíntese
3.
Int J Mol Sci ; 25(8)2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38674054

RESUMO

Neuregulin-1 (Nrg1, gene symbol: Nrg1), a ligand of the ErbB receptor family, promotes intestinal epithelial cell proliferation and repair. However, the dynamics and accurate derivation of Nrg1 expression during colitis remain unclear. By analyzing the public single-cell RNA-sequencing datasets and employing a dextran sulfate sodium (DSS)-induced colitis model, we investigated the cell source of Nrg1 expression and its potential regulator in the process of epithelial healing. Nrg1 was majorly expressed in stem-like fibroblasts arising early in mouse colon after DSS administration, and Nrg1-Erbb3 signaling was identified as a potential mediator of interaction between stem-like fibroblasts and colonic epithelial cells. During the ongoing colitis phase, a significant infiltration of macrophages and neutrophils secreting IL-1ß emerged, accompanied by the rise in stem-like fibroblasts that co-expressed Nrg1 and IL-1 receptor 1. By stimulating intestinal or lung fibroblasts with IL-1ß in the context of inflammation, we observed a downregulation of Nrg1 expression. Patients with inflammatory bowel disease also exhibited an increase in NRG1+IL1R1+ fibroblasts and an interaction of NRG1-ERBB between IL1R1+ fibroblasts and colonic epithelial cells. This study reveals a novel potential mechanism for mucosal healing after inflammation-induced epithelial injury, in which inflammatory myeloid cell-derived IL-1ß suppresses the early regeneration of intestinal tissue by interfering with the secretion of reparative neuregulin-1 by stem-like fibroblasts.


Assuntos
Colite , Sulfato de Dextrana , Fibroblastos , Mucosa Intestinal , Neuregulina-1 , Transdução de Sinais , Animais , Humanos , Masculino , Camundongos , Colite/metabolismo , Colite/induzido quimicamente , Colite/patologia , Sulfato de Dextrana/efeitos adversos , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Células Epiteliais/metabolismo , Fibroblastos/metabolismo , Interleucina-1beta/metabolismo , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Camundongos Endogâmicos C57BL , Células Mieloides/metabolismo , Neuregulina-1/metabolismo , Neuregulina-1/genética , Receptor ErbB-3/metabolismo , Receptor ErbB-3/genética , Receptores Tipo I de Interleucina-1/metabolismo , Receptores Tipo I de Interleucina-1/genética
4.
Int J Mol Sci ; 25(9)2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38732173

RESUMO

Lung adenocarcinoma (LUAD) is the most prevalent and aggressive subtype of lung cancer, exhibiting a dismal prognosis with a five-year survival rate below 5%. DEAD-box RNA helicase 18 (DDX18, gene symbol DDX18), a crucial regulator of RNA metabolism, has been implicated in various cellular processes, including cell cycle control and tumorigenesis. However, its role in LUAD pathogenesis remains elusive. This study demonstrates the significant upregulation of DDX18 in LUAD tissues and its association with poor patient survival (from public databases). Functional in vivo and in vitro assays revealed that DDX18 knockdown potently suppresses LUAD progression. RNA sequencing and chromatin immunoprecipitation experiments identified cyclin-dependent kinase 4 (CDK4), a cell cycle regulator, as a direct transcriptional target of DDX18. Notably, DDX18 depletion induced G1 cell cycle arrest, while its overexpression promoted cell cycle progression even in normal lung cells. Interestingly, while the oncogenic protein c-Myc bound to the DDX18 promoter, it did not influence its expression. Collectively, these findings establish DDX18 as a potential oncogene in LUAD, functioning through the CDK4-mediated cell cycle pathway. DDX18 may represent a promising therapeutic target for LUAD intervention.


Assuntos
Adenocarcinoma de Pulmão , Quinase 4 Dependente de Ciclina , RNA Helicases DEAD-box , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares , Animais , Humanos , Camundongos , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/metabolismo , Carcinogênese/genética , Carcinogênese/metabolismo , Ciclo Celular/genética , Linhagem Celular Tumoral , Proliferação de Células , Quinase 4 Dependente de Ciclina/metabolismo , Quinase 4 Dependente de Ciclina/genética , RNA Helicases DEAD-box/metabolismo , RNA Helicases DEAD-box/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Camundongos Nus , Regulação para Cima
5.
BMC Med ; 21(1): 179, 2023 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-37170220

RESUMO

BACKGROUND: Oxidative stress (OS) is a key pathophysiological mechanism in Crohn's disease (CD). OS-related genes can be affected by environmental factors, intestinal inflammation, gut microbiota, and epigenetic changes. However, the role of OS as a potential CD etiological factor or triggering factor is unknown, as differentially expressed OS genes in CD can be either a cause or a subsequent change of intestinal inflammation. Herein, we used a multi-omics summary data-based Mendelian randomization (SMR) approach to identify putative causal effects and underlying mechanisms of OS genes in CD. METHODS: OS-related genes were extracted from the GeneCards database. Intestinal transcriptome datasets were collected from the Gene Expression Omnibus (GEO) database and meta-analyzed to identify differentially expressed genes (DEGs) related to OS in CD. Integration analyses of the largest CD genome-wide association study (GWAS) summaries with expression quantitative trait loci (eQTLs) and DNA methylation QTLs (mQTLs) from the blood were performed using SMR methods to prioritize putative blood OS genes and their regulatory elements associated with CD risk. Up-to-date intestinal eQTLs and fecal microbial QTLs (mbQTLs) were integrated to uncover potential interactions between host OS gene expression and gut microbiota through SMR and colocalization analysis. Two additional Mendelian randomization (MR) methods were used as sensitivity analyses. Putative results were validated in an independent multi-omics cohort from the First Affiliated Hospital of Sun Yat-sen University (FAH-SYS). RESULTS: A meta-analysis from six datasets identified 438 OS-related DEGs enriched in intestinal enterocytes in CD from 817 OS-related genes. Five genes from blood tissue were prioritized as candidate CD-causal genes using three-step SMR methods: BAD, SHC1, STAT3, MUC1, and GPX3. Furthermore, SMR analysis also identified five putative intestinal genes, three of which were involved in gene-microbiota interactions through colocalization analysis: MUC1, CD40, and PRKAB1. Validation results showed that 88.79% of DEGs were replicated in the FAH-SYS cohort. Associations between pairs of MUC1-Bacillus aciditolerans and PRKAB1-Escherichia coli in the FAH-SYS cohort were consistent with eQTL-mbQTL colocalization. CONCLUSIONS: This multi-omics integration study highlighted that OS genes causal to CD are regulated by DNA methylation and host-microbiota interactions. This provides evidence for future targeted functional research aimed at developing suitable therapeutic interventions and disease prevention.


Assuntos
Doença de Crohn , Microbioma Gastrointestinal , Humanos , Doença de Crohn/genética , Estudo de Associação Genômica Ampla , Metilação de DNA/genética , Microbioma Gastrointestinal/genética , Análise da Randomização Mendeliana/métodos , Multiômica , Transcriptoma , Inflamação , Estresse Oxidativo/genética
6.
J Immunol ; 206(9): 1991-2000, 2021 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-33827895

RESUMO

Asthma is an allergic chronic respiratory disease that affects more than 300 million people around the world. Dysbiosis of intestinal commensal microbiota influences the development of asthma. Dectin-1 (gene symbol: Clec7a), a C-type lectin receptor, plays an important role in the intestinal immune homeostasis by controlling regulatory T (Treg) cell differentiation through regulation of intestinal microbiota. However, it is not clear whether intestinal immune conditions affect immune responses in other organs. In this study, we examined the effects of Dectin-1 deficiency on allergic airway inflammation (AAI). OVA-induced AAI was attenuated in Clec7a -/- mice. Treg cells were more abundant in colonic lamina propria, mesenteric lymph nodes, and bronchoalveolar lavage fluid of Clec7a -/- mice after AAI induction. Treatment with antibiotics, but not an antifungal agent, decreased the abundance of intestinal Treg cells and aggravated the symptoms of AAI in Clec7a -/- mice. Transplantation of gut microbiota from Clec7a -/- mice into antibiotic-treated hosts increased the abundance of intestinal Treg cells and ameliorated AAI. Overcolonization by Lactobacillus murinus, a Dectin-1 signaling-regulated commensal bacterium, also promoted expansion of Treg cells in the colon and suppressed lung inflammation. Depletion of Treg cells with anti-CD25 Ab eliminated the phenotypic differences between wild-type and Clec7a -/- mice in OVA-induced AAI. These observations suggest that inhibition of Dectin-1 signaling ameliorates AAI by increasing the abundance of Treg cells in lungs through modification of intestinal commensal bacteria, suggesting a role for commensal microbiota in regulating inflammation in organs other than the intestine.


Assuntos
Intestinos/imunologia , Lectinas Tipo C/deficiência , Pulmão/imunologia , Ovalbumina/imunologia , Pneumonia/imunologia , Linfócitos T Reguladores/imunologia , Animais , Bactérias/classificação , Bactérias/genética , Bactérias/imunologia , Líquido da Lavagem Broncoalveolar/imunologia , Microbioma Gastrointestinal/imunologia , Hipersensibilidade/genética , Hipersensibilidade/imunologia , Intestinos/microbiologia , Lactobacillus/imunologia , Lactobacillus/fisiologia , Lectinas Tipo C/genética , Pulmão/metabolismo , Camundongos Endogâmicos BALB C , Camundongos Knockout , Pneumonia/genética , RNA Ribossômico 16S/genética , Linfócitos T Reguladores/metabolismo
7.
Zhongguo Zhong Yao Za Zhi ; 47(4): 1001-1008, 2022 Feb.
Artigo em Zh | MEDLINE | ID: mdl-35285200

RESUMO

Ultra-high performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry(UPLC-Q-TOF/MS) was used to investigate the effect of Pterocephalus hookeri on serum metabolism of adjuvant arthritis(AA) model rats induced by complete Freund's adjuvant. After the AA model was properly induced, the serum of rats was collected 30 days after treatment. UPLC-Q-TOF-MS chromatograms were collected and analyzed by principal component analysis(PCA) and orthogonal partial least squares discriminant analysis(OPLS-DA). The results revealed that compared with the control group, the model group showed increased content of 12 biomarkers in the serum(P<0.05) and reduced content of the other nine biomarkers(P<0.05). P. hookeri extract could recover the above-mentioned 19 biomarkers to a certain range. Pathway enrichment showed that these markers mainly involved eight metabolic pathways, including valine, leucine, and isoleucine degradation, arachidonic acid metabolism, arginine and proline metabolism, glycerol phospholipid metabolism, primary bile acid biosynthesis, bile acid biosynthesis, tryptophan metabolism, and unsaturated fatty acid biosynthesis. The findings of this study demonstrate that P. hookeri extract can regulate metabolic disorders and promote the regression of metabolic phenotype to the normal level to exert the therapeutic effect on AA rats. This study is expected to provide a certain scientific basis for the biological research on the treatment of rheumatoid arthritis by P. hookeri.


Assuntos
Artrite Reumatoide , Medicamentos de Ervas Chinesas , Animais , Artrite Reumatoide/tratamento farmacológico , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/farmacologia , Medicina Tradicional Tibetana , Metabolômica , Ratos
8.
Zhongguo Zhong Yao Za Zhi ; 47(16): 4333-4340, 2022 Aug.
Artigo em Zh | MEDLINE | ID: mdl-36046859

RESUMO

The quality of Paeoniae Radix Alba and Paeoniae Radix Rubra is evaluated by root thickness, and paeoniflorin serves as a common quality indicator of them. However, the correlation between the content of bioactive compounds and the root size is still unclear. Therefore, this study characterized the distribution patterns and content of seven bioactive compounds including paeoniflorin in different tissues of Paeonia lactiflora roots, analyzed the correlation between the root size and the content of bioactive compounds based on the xylem-to-bark ratio, and further determined the index components for quality assessment. Nine samples of fresh P. lactiflora roots were collected from the genuine cultivation area. The distribution of bioactive compounds in different tissues on the cross-section of the root was firstly analyzed by desorption electrospray ionization-mass spectrometry imaging(DESI-MSI). Subsequently, the content of bioactive compounds was determined in the xylems and barks of the roots by UPLC. The compounds with the largest difference between the xylem and the bark were selected by orthogonal partial least squares discriminant analysis(OPLS-DA). The results indicated that paeoniflorin, benzoylpaeoniflorin, oxypaeoniflorin, gallic acid, and 1,2,3,4,6-pentagalloylglucose were significantly accumulated in the xylems, while albiflorin and catechin were mainly distributed in the barks. Paeoniflorin and albiflorin, with the largest differences in the xylem and the bark, had the highest content in the two tissues. The root diameter was positively correlated with paeoniflorin content and negatively correlated with albiflorin content. As isomers with different efficacies, paeoniflorin or albiflorin can be chosen as the quality marker corresponding to specific clinical application to launch quality classification evaluation of multi-functional Chinese medicines.


Assuntos
Catequina , Paeonia , Hidrocarbonetos Aromáticos com Pontes , Catequina/análise , Cromatografia Líquida de Alta Pressão/métodos , Ácido Gálico/análise , Monoterpenos/análise , Paeonia/química , Raízes de Plantas/química , Espectrometria de Massas por Ionização por Electrospray
9.
Immunity ; 37(6): 957-9, 2012 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-23244717

RESUMO

Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastrointestinal tract. In this issue of Immunity, Griseri et al. (2012) show that IL-23-induced dysregulation of hematopoietic stem and progenitor cells contributes to the pathogenesis of two IBD models.

10.
Immunity ; 37(1): 74-84, 2012 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-22727489

RESUMO

Epithelial keratinocyte proliferation is an essential element of wound repair, and abnormal epithelial proliferation is an intrinsic element in the skin disorder psoriasis. The factors that trigger epithelial proliferation in these inflammatory processes are incompletely understood. Here we have shown that regenerating islet-derived protein 3-alpha (REG3A) is highly expressed in keratinocytes during psoriasis and wound repair and in imiquimod-induced psoriatic skin lesions. The expression of REG3A by keratinocytes is induced by interleukin-17 (IL-17) via activation of keratinocyte-encoded IL-17 receptor A (IL-17RA) and feeds back on keratinocytes to inhibit terminal differentiation and increase cell proliferation by binding to exostosin-like 3 (EXTL3) followed by activation of phosphatidylinositol 3 kinase (PI3K) and the kinase AKT. These findings reveal that REG3A, a secreted intestinal antimicrobial protein, can promote skin keratinocyte proliferation and can be induced by IL-17. This observation suggests that REG3A may mediate the epidermal hyperproliferation observed in normal wound repair and in psoriasis.


Assuntos
Antígenos de Neoplasias/metabolismo , Biomarcadores Tumorais/metabolismo , Diferenciação Celular , Queratinócitos/citologia , Queratinócitos/metabolismo , Lectinas Tipo C/metabolismo , Pele/lesões , Pele/metabolismo , Animais , Antígenos de Neoplasias/genética , Biomarcadores Tumorais/genética , Diferenciação Celular/genética , Proliferação de Células , Epiderme/efeitos dos fármacos , Epiderme/lesões , Epiderme/metabolismo , Expressão Gênica/efeitos dos fármacos , Humanos , Interleucina-17/farmacologia , Queratinócitos/efeitos dos fármacos , Lectinas Tipo C/genética , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , N-Acetilglucosaminiltransferases/metabolismo , Proteínas Associadas a Pancreatite , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas/genética , Proteínas/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Psoríase/imunologia , Psoríase/metabolismo , Psoríase/patologia , Transdução de Sinais , Pele/efeitos dos fármacos , Cicatrização/genética
11.
J Asian Nat Prod Res ; 23(12): 1189-1196, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33327766

RESUMO

This work obtained and identified pterocephanoside A (1), one new iridoid glucoside derivative with rare structure of three iridoid glycosides linked to cyclopenta[c]pyran-3(1H)-one, and 10 known iridoids (2-11) from Pterocephalus hookeri through silica gel column chromatography and semi-preparative HPLC. The structure of the new compound was confirmed by 1D and 2D NMR and HRMS data analysis. Compounds 1 and 2 were isolated from this plant for the first time. The iridoids mostly possessed seco-iridoid subtype and iridoid subtype skeletons from P. hookeri. Compounds 1, 3, 4, and 6-11 showed weak anti-inflammatory activity.


Assuntos
Caprifoliaceae , Medicina Tradicional Tibetana , Glicosídeos Iridoides , Iridoides , Estrutura Molecular
12.
Zhongguo Zhong Yao Za Zhi ; 44(15): 3157-3161, 2019 Aug.
Artigo em Zh | MEDLINE | ID: mdl-31602867

RESUMO

In order to study the interaction between Pterocephalus hookeri and bitter taste receptors,three-dimensional structural models of bitter taste receptors TAS2 R16,TAS2 R14 and TAS2 R13 were established by homology modeling in this paper. Maestro software was used for docking the chemical constituents of P. hookeri with bitter taste receptors. The results showed that 25 chemical components of P. hookeri can regulate three bitter taste receptors. And these components were mainly iridoid glycosides and phenolic acids.This research focused on the comprehensive application of homology modeling and molecular docking technology to explore the interaction between bitter chemical constituents of P. hookeri and bitter taste receptors. This study provided assistance in revealing pharmacodynamic basis of bitter Tibetan medicine at molecular level. It also provided new ideas and methods for the study of Tibetan medicine.


Assuntos
Caprifoliaceae/química , Medicina Tradicional Tibetana , Simulação de Acoplamento Molecular , Receptores Acoplados a Proteínas G/metabolismo , Correlação de Dados , Humanos , Paladar
13.
Zhongguo Zhong Yao Za Zhi ; 44(15): 3170-3177, 2019 Aug.
Artigo em Zh | MEDLINE | ID: mdl-31602869

RESUMO

The intestinal absorption characteristics of ten iridoid glycosides and phenolic acids in the Pterocephali Herba were evaluated via rat intestinal valgus model. The intestinal sac fluids at different time after administration of high,medium and low concentrations of Pterocephali Herba extract were collected and ten chemical components in fluid samples were detected by UPLC-PDA. Accumulative absorbed doses( Q) and absorption rate constants( Ka) of ten chemical constituents were calculated,while proportions between Pterocephali Herba extract and intestinal absorption liquid were compared. The results showed that the intestinal absorption of 10 chemical components was linear absorption( R2>0. 9) at different concentrations,which accorded with the zero-order absorption rate. The absorption rate constant was related to the concentration of the drug and the intestinal site,which indicated that intestinal adsorption mechanism of the components were passive diffusion and active transport. Proportions of chemical constituents in intestinal sac fluid were different from those in Pterocephali Herba extract. Therefore,those ten chemical components in Pterocephali Herba extract can be absorbed in whole intestine. Everted intestinal sac model can be used to evaluate intestinal absorption characteristics of ingredients in Pterocephali Herba extract effectively.


Assuntos
Caprifoliaceae/química , Medicamentos de Ervas Chinesas/farmacocinética , Absorção Intestinal , Extratos Vegetais/farmacocinética , Animais , Intestinos , Ratos , Ratos Sprague-Dawley
14.
Biochem Biophys Res Commun ; 496(3): 934-940, 2018 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-29366788

RESUMO

Ulcerative colitis (UC) is an inflammatory disease of the colon. IL1R2, which encodes IL-1 receptor type 2 (IL-1R2), was reported as a risk gene for UC. To elucidate the roles of IL-1R2 in the development of colitis, we examined the development of dextran sodium sulfate-induced colitis, a mouse model for UC using Il1r2-/- mice. We found the severity score of colitis was milder in Il1r2-/- mice compared with wild-type (WT) mice when they were housed separately, however the severity score was similar when they were housed in a cage. In the separate housing condition, relative contents of Actinobacteria and Bacilli in feces of Il1r2-/- mice were lower than that of WT mice. Furthermore, IL-1ß induced the expression of antimicrobial peptides (AMPs) from colon. Thus, we show that IL-1R2 is harmful for the development of colitis, because IL-1R2 promotes the growth of proinflammatory intestinal microbiota by suppressing IL-1ß-induced AMP production.


Assuntos
Peptídeos Catiônicos Antimicrobianos/imunologia , Colite/imunologia , Microbioma Gastrointestinal/imunologia , Receptores de Interleucina-1/imunologia , Animais , Colite/induzido quimicamente , Colite/patologia , Sulfato de Dextrana , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Receptores de Interleucina-1/genética
15.
Pharm Biol ; 55(1): 560-570, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27937009

RESUMO

CONTEXT: Pterocephalus hookeri (C. B. Clarke) Hock., a traditional Tibetan herbal medicine rich in glycosides, has been used to treat several diseases including rheumatoid arthritis. OBJECTIVE: To evaluate the anti-arthritic activity of total glycosides from P. hookeri, and its possible mechanisms of action. MATERIALS AND METHODS: Anti-arthritic activity of total glycosides from P. hookeri (oral administration for 30 days at 14-56 mg/kg) was evaluated using paw swelling, arthritis scores and histopathological measurement in adjuvant-induced arthritis (AA) Sprague-Dawley rats. The NF-κB p65 expression in synovial tissues, and serum superoxide dismutase (SOD) activity, malondialdehyde (MDA) and nitric oxide (NO) levels was measured in AA rats, respectively. Further assessment of anti-inflammatory and analgesic activities of these glycosides were carried out using inflammation and hyperalgesia models induced by xylene, carrageenan, agar and acetic acid, respectively. RESULTS: Total glycosides (56 mg/kg) decreased the paw swelling (38.0%, p < 0.01), arthritis scores (25.3%, p < 0.01) and synovial inflammation in AA rats. The glycosides significantly (p < 0.05-0.01) attenuated the inflammation induced by xylene, carrageenan, acetic acid and agar, increased the pain threshold in acetic acid-induced writhing in mice and mechanical stimuli-induced hyperalgia in AA rats. The glycosides (14, 28, 56 mg/kg) also suppressed the NF-κB p65 expression (33.1-78.2%, p < 0.05-0.01), reduced MDA (21.3-35.9%, p < 0.01) and NO (20.3-32.4%, p < 0.05-0.01) levels, respectively, enhanced the SOD activity (7.8%, p < 0.05) at 56 mg/kg in AA rats. DISCUSSION AND CONCLUSION: Our findings confirmed the anti-arthritic property of the total glycosides from P. hookeri, which may be attributed to its inhibition on NF-κB signalling and oxidative stress.


Assuntos
Anti-Inflamatórios/farmacologia , Artrite Experimental/tratamento farmacológico , Caprifoliaceae/química , Glicosídeos/farmacologia , Articulações/efeitos dos fármacos , Preparações de Plantas/farmacologia , Analgésicos/isolamento & purificação , Analgésicos/farmacologia , Animais , Anti-Inflamatórios/isolamento & purificação , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Artrite Experimental/induzido quimicamente , Artrite Experimental/metabolismo , Artrite Experimental/patologia , Comportamento Animal/efeitos dos fármacos , Biomarcadores/sangue , Relação Dose-Resposta a Droga , Edema/induzido quimicamente , Edema/prevenção & controle , Feminino , Adjuvante de Freund , Glicosídeos/isolamento & purificação , Hiperalgesia/induzido quimicamente , Hiperalgesia/fisiopatologia , Hiperalgesia/prevenção & controle , Mediadores da Inflamação/sangue , Articulações/metabolismo , Articulações/patologia , Masculino , Malondialdeído/sangue , Medicina Tradicional Tibetana , Camundongos , Óxido Nítrico/sangue , Limiar da Dor/efeitos dos fármacos , Fitoterapia , Preparações de Plantas/isolamento & purificação , Plantas Medicinais , Ratos Sprague-Dawley , Superóxido Dismutase/sangue , Fatores de Tempo , Fator de Transcrição RelA/metabolismo
16.
Zhongguo Zhong Yao Za Zhi ; 42(10): 1871-1876, 2017 May.
Artigo em Zh | MEDLINE | ID: mdl-29090545

RESUMO

In order to study the ecology suitability of Pterocephalus hookeri, and provide a reference for GAP planting location and regional development, the Maxent model and GIS technology were used to investigate ecology suitability regions for P. hookeri based on the distribution points collected from Chinese virtual herbarium, the references and field trips. The potential distribution areas mainly concentrated in the eastern Tibet, western Sichuan, southern Qinghai, northwest Yunnan, and southern Gansu. There were 7 major environmental factors to have obvious influence on ecology suitability distributions of P. hookeri, including altitude (contribution rate of 62%), precipitation of warmest quarter (contribution rate of 14.4%), coefficient of variation of precipitation seasonality (contribution rate of 7.2%), mean temperature of driest quarter (contribution rate of 3.5%), the electrical conductivity of top and sub-soil (contribution rate of 3%), the total exchangeable bases in the top- and subsoil (contribution rate of 2.4%) and SD of temperature seasonality (contribution rate of 2.2%). The study of the ecological suitability regionalization of P. hookeri based on Maxent model can provide scientific basis for the selection of artificial planting base and GAP planting location.


Assuntos
Caprifoliaceae/crescimento & desenvolvimento , Clima , Ecologia , Plantas Medicinais/crescimento & desenvolvimento , China , Sistemas de Informação Geográfica , Dispersão Vegetal , Solo , Tibet
17.
Zhongguo Zhong Yao Za Zhi ; 42(7): 1234-1237, 2017 Apr.
Artigo em Zh | MEDLINE | ID: mdl-29052379

RESUMO

This study is to develop an UPLC-PDA method for determination of 10 major components in Pterocephalus. The UPLC-PDA assay was performed on a Waters Acquity UPLCR BEH C18(2.1 mm ×100 mm,1.7 µm), and the column temperature was at 30 ℃. The mobile phase consists of water containing 0.2% phosphoric acid (A) and acetonitrile (B) in gradient elution at a flow rate of 0.4 mL•min⁻¹. The detection wave length was set at 237 and 325 nm, and the injection volume was 1 µL in the UPLC system. The linear range of 10 detected compounds were good (r≥0.999 7), and the overall recoveries ranged from 96.30% to 103.0%, with the RSD ranging from 0.72% to 2.9%. The method was simple, accurate and reproducible, which can be used for the simultaneous determination of the content of ten major components in P. hookeri.


Assuntos
Caprifoliaceae/química , Hidroxibenzoatos/isolamento & purificação , Glicosídeos Iridoides/isolamento & purificação , Cromatografia Líquida de Alta Pressão
18.
Zhongguo Zhong Yao Za Zhi ; 42(16): 3213-3218, 2017 Aug.
Artigo em Zh | MEDLINE | ID: mdl-29171243

RESUMO

This study was aimed to discuss and analyze the medication rules for prescriptions containing Pterocephali Herba in Chinese Medical Encyclopedia - Tibetan Medicine, Tibetan Medicine Prescription Modern Research and Clinical Application, and Interpretation of Common Tibetan Medicines based on the collection of Pterocephali Herba and by using the "Traditional Chinese Medicine Inheritance Support system(V2.0.1)",with the use of association rules, apriori algorithm and other data mining methods. The frequency of single drug, the frequency of drug combination, the association rule and the combination of core drugs were analyzed. Through collection of the prescriptions, a total of 215 prescriptions were included, involving a total of 376 herbs. Through the "frequency statistics", the prescriptions containing Pterocephali Herba were commonly used to treat cold fever, distemper virus and arthritis. The highest frequently (frequency≥15) used drugs were Corydalis Herba, Lagotidis Herba, and Gentianae Macrophyllae Radix, et al. The most frequently used drug combinations were "Pterocephali Herba, Corydalis Herba","Pterocephali Herba, Lagotidis Herba", and "Pterocephali Herba, Gentianae Macrophyllae Radix" et al. The prescriptions containing Pterocephali Herba were used to primarily treat disease for Tourette syndrome caused by the dampness heat toxin, fever, arthritis etc, such as pestilent toxicity, pneumonia and influenza, rheumatoid arthritis etc. The drugs in the prescriptions mostly had the effects of heat-clearing and detoxifying, anti-inflammatory, dispelling wind and dampness, often in compatible use with heat-clearing drugs. The drug use was concentrated and reflected the clear thought of prescription statutes.


Assuntos
Mineração de Dados , Medicamentos de Ervas Chinesas/normas , Medicina Tradicional Tibetana/normas , Prescrições de Medicamentos
19.
Pharm Biol ; 54(12): 3264-3271, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27569515

RESUMO

CONTEXT: Rhizoma coptidis is a broadly used traditional Chinese medicine (TCM). The investigation of the influence of species and geographical origins on the phytochemicals of R. coptidis is crucial for its reasonable application and quality control. OBJECTIVE: Development of an effective method to systematically study the phytochemical variations of the rhizomes of three Coptis species (Ranunculaceae) (Coptis chinensis Franch, Coptis deltoidea C.Y. Cheng et Hsiao and Coptis teeta Wall.) and a species (i.e., C. chinensis) obtained from both Daodi and non-Daodi production regions. RESULTS: The three species had significant differences in their phytochemicals. The rhizome of C. chinensis contained more epiberberine (13.52 ± 2.65 mg/g), palmatine (18.20 ± 2.89 mg/g), coptisine (23.32 ± 4.27 mg/g) and columbamine (4.89 ± 1.16 mg/g), whereas the rhizomes of C. deltoidea and C. teeta showed the highest level of jatrorrhizine (8.52 ± 1.36 mg/g) and berberine (81.06 ± 4.83 mg/g), respectively. Moreover, the rhizome of C. chinensis from three Daodi production regions (Shizhu, Lichuan and Emeishan) contained more alkaloids than those from three non-Daodi production regions (Mianyang, Shifang and Zhenping). DISCUSSION AND CONCLUSION: It is necessary to use the three R. coptidis species differentially in TCM clinical practice. Daodi C. chinensis medicinal materials have better quality than most non-Daodi ones, and so they should be preferred for TCM prescription. The combination of HPLC-based fingerprint analysis and quantification of multi-ingredients with statistical analysis provided an effective approach for species discrimination and quality evaluation of R. coptidis.


Assuntos
Medicamentos de Ervas Chinesas/análise , Mapeamento de Peptídeos/métodos , Extratos Vegetais/análise , Extratos Vegetais/genética , Ranunculaceae/genética , Rizoma , Cromatografia Líquida de Alta Pressão/métodos , Especificidade da Espécie
20.
Am J Emerg Med ; 33(7): 931-6, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25937378

RESUMO

OBJECTIVE: The question of whether the placement of the dominant hand against the sternum could improve the quality of manual chest compressions remains controversial. In the present study, we evaluated the influence of dominant vs nondominant hand positioning on the quality of conventional cardiopulmonary resuscitation (CPR) during prolonged basic life support (BLS) by rescuers who performed optimal and suboptimal compressions. METHODS: Six months after completing a standard BLS training course, 101 medical students were instructed to perform adult single-rescuer BLS for 8 minutes on a manikin with a randomized hand position. Twenty-four hours later, the students placed the opposite hand in contact with the sternum while performing CPR. Those with an average compression depth of less than 50 mm were considered suboptimal. RESULTS: Participants who had performed suboptimal compressions were significantly shorter (170.2 ± 6.8 vs 174.0 ± 5.6 cm, P = .008) and lighter (58.9 ± 7.6 vs 66.9 ± 9.6 kg, P < .001) than those who performed optimal compressions. No significant differences in CPR quality were observed between dominant and nondominant hand placements for these who had an average compression depth of greater than 50 mm. However, both the compression depth (49.7 ± 4.2 vs 46.5 ± 4.1 mm, P = .003) and proportion of chest compressions with an appropriate depth (47.6% ± 27.8% vs 28.0% ± 23.4%, P = .006) were remarkably higher when compressing the chest with the dominant hand against the sternum for those who performed suboptimal CPR. CONCLUSIONS: Chest compression quality significantly improved when the dominant hand was placed against the sternum for those who performed suboptimal compressions during conventional CPR.


Assuntos
Reanimação Cardiopulmonar/educação , Massagem Cardíaca/métodos , Manequins , Melhoria de Qualidade , Reanimação Cardiopulmonar/métodos , Reanimação Cardiopulmonar/normas , Estudos Cross-Over , Método Duplo-Cego , Feminino , Massagem Cardíaca/normas , Humanos , Masculino , Adulto Jovem
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