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1.
Spinal Cord ; 62(8): 429-439, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38849489

RESUMO

STUDY DESIGN: Animal studies OBJECTIVES: To evaluate the therapeutic effect of olfactory mucosa mesenchymal stem cell (OM-MSCs) transplantation in mice with spinal cord injury (SCI) and to explore the mechanism by which OM-MSCs inhibit neuroinflammation and improve SCI. SETTING: Xiangya Hospital, Central South University; Affiliated Hospital of Guangdong Medical University. METHODS: Mice (C57BL/6, female, 6-week-old) were randomly divided into sham, SCI, and SCI + OM-MSC groups. The SCI mouse model was generated using Allen's method. OM-MSCs were immediately delivered to the lateral ventricle after SCI using stereotaxic brain injections. One day prior to injury and on days 1, 5, 7, 14, 21, and 28 post-injury, the Basso Mouse Scale and Rivlin inclined plate tests were performed. Inflammation and microglial polarization were evaluated using histological staining, immunofluorescence, and qRT-PCR. RESULTS: OM-MSCs originating from the neuroectoderm have great potential in the management of SCI owing to their immunomodulatory effects. OM-MSCs administration improved motor function, alleviated inflammation, promoted the transformation of the M1 phenotype of microglia into the M2 phenotype, facilitated axonal regeneration, and relieved spinal cord injury in SCI mice. CONCLUSIONS: OM-MSCs reduced the level of inflammation in the spinal cord tissue, protected neurons, and repaired spinal cord injury by regulating the M1/M2 polarization of microglia.


Assuntos
Transplante de Células-Tronco Mesenquimais , Camundongos Endogâmicos C57BL , Microglia , Mucosa Olfatória , Traumatismos da Medula Espinal , Animais , Traumatismos da Medula Espinal/terapia , Traumatismos da Medula Espinal/patologia , Transplante de Células-Tronco Mesenquimais/métodos , Mucosa Olfatória/citologia , Microglia/fisiologia , Camundongos , Feminino , Modelos Animais de Doenças , Células-Tronco Mesenquimais/fisiologia , Recuperação de Função Fisiológica/fisiologia , Polaridade Celular/fisiologia
2.
Molecules ; 28(3)2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36770726

RESUMO

Cepharanthine (CEP), a bisbenzylisoquinoline alkaloid from tubers of Stephania, protects against some inflammatory diseases. Aconitate decarboxylase 1 (ACOD1) is also known as immune-responsive gene 1 (IRG1), which plays an important immunometabolism role in inflammatory diseases by mediating the production of itaconic acid. ACOD1 exhibits abnormal expression in ulcerative colitis (UC). However, whether CEP can combat UC by affecting ACOD1 expression remains unanswered. This study was designed to explore the protective effects and mechanisms of CEP in treating colitis through in vitro and in vivo experiments. In vitro assays indicated that CEP inhibited LPS-induced secretion of pro-inflammatory cytokines and ACOD1 expression in RAW264.7 macrophages. Additionally, in the mouse model of DSS-induced colitis, CEP decreased macrophage infiltration and ACOD1 expression in colon tissue. After treatment with antibiotics (Abx), the expression of ACOD1 changed with the composition of gut microbiota. Correlation analysis also revealed that Family-XIII-AD3011-group and Rumini-clostridium-6 were positively correlated with ACOD1 expression level. Additionally, data of the integrative Human Microbiome Project (iHMP) showed that ACOD1 was highly expressed in the colon tissue of UC patients and this expression was positively correlated with the severity of intestinal inflammation. Collectively, CEP can counter UC by modulating gut microbiota and inhibiting the expression of ACOD1. CEP may serve as a potential pharmaceutical candidate in the treatment of UC.


Assuntos
Benzilisoquinolinas , Colite Ulcerativa , Colite , Animais , Camundongos , Humanos , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/metabolismo , Macrófagos , Colo/metabolismo , Benzilisoquinolinas/farmacologia , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Colite/metabolismo , Camundongos Endogâmicos C57BL
3.
Int J Colorectal Dis ; 37(4): 769-775, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35325272

RESUMO

BACKGROUND: Growing evidence indicates that inflammatory bowel disease (IBD) and dementia share similar pathological mechanisms, but no consensus has yet emerged on the effect that IBD and dementia are associated. To explore such a possible correlation, we summarize herein the epidemiological evidence. We subject relevant studies to meta-analysis. METHODS: We comprehensively searched Pubmed and Embase for relevant articles published to Dec 2021. The pooled risk ratio (RR) with the 95% confidence interval (CI) was used to estimate the effect; we calculated the generic inverse variance using a random-effects model. RESULTS: Seven studies involving 65,454 patients with dementia were included in the meta-analysis. The overall risk of dementia in IBD patients was significantly higher than that in the general population (risk ratio [RR], 1.35; 95% confidence interval [CI], 1.08-1.68; P = 0.008). The results of subgroup analyses were consistent with the overall results. The risk of Alzheimer's disease was higher in IBD patients (RR = 2.79, 95% CI = 1.1, 7.04; P < 0.001). CONCLUSIONS: Our results revealed that IBD may be a potential risk indicator for dementia.


Assuntos
Colite , Demência , Doenças Inflamatórias Intestinais , Demência/epidemiologia , Demência/etiologia , Humanos , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/epidemiologia , Razão de Chances , Fatores de Risco
4.
Gastroenterol Res Pract ; 2024: 6634377, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38989159

RESUMO

Background: Patients with inflammatory bowel disease (IBD) often experience worries related to travel due to frequent bowel movements. However, there is currently limited research focusing on the travel worries of patients with IBD. The aim of this study was to assess the level of worry regarding out-of-home activities in patients with IBD and identify factors associated with worry. Methods: This study included patients with IBD who visited the outpatient clinics between September 2020 and March 2022, during the COVID-19 pandemic. Participants completed a self-designed questionnaire, providing general clinical data and indicating their level of worry for out-of-home activities. Results: A total of 529 patients with IBD completed the questionnaire. Patients with Crohn's disease (CD) had a higher proportion of individuals under 40 years old and males compared to patients with ulcerative colitis (UC). Regarding out-of-home activities, patients with UC expressed greater worry about going out and taking buses than patients with CD. However, there were no significant differences observed between the two groups in terms of travel worries and worries about finding public washrooms. A significant majority (85.4%) of patients with clinically active IBD expressed worries about not finding public washrooms when going out, while 46.7% of patients in clinical remission had similar worries. Moreover, the worry about finding public washrooms was higher in patients with UC compared to those with CD, both during the clinical activity and remission. Conclusion: This survey conducted during the COVID-19 pandemic reported worries among patients with IBD about out-of-home activities. The patients with clinically active IBD, especially UC, expressed worries about not finding public washrooms when going out. We highlight the actual psychological and quality of life challenges faced by patients with IBD.

5.
World J Gastroenterol ; 29(30): 4657-4670, 2023 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-37662857

RESUMO

BACKGROUND: Fecal microbiota transplantation (FMT) has shown promising therapeutic effects on mice with experimental colitis and patients with ulcerative colitis (UC). FMT modulates the Toll-like receptor 4 (TLR4) signaling pathway to treat some other diseases. However, it remains unknown whether this modulation is also involved in the treatment of UC. AIM: To clarify the necessity of TLR4 signaling pathway in FMT on dextran sodium sulphate (DSS)-induced mice and explain the mechanism of FMT on UC, through association analysis of gut microbiota with colon transcriptome in mice. METHODS: A mouse colitis model was constructed with wild-type (WT) and TLR4-knockout (KO) mice. Fecal microbiota was transplanted by gavage. Colon inflammation severity was measured by disease activity index (DAI) scoring and hematoxylin and eosin staining. Gut microbiota structure was analyzed through 16S ribosomal RNA sequencing. Gene expression in the mouse colon was obtained by transcriptome sequencing. RESULTS: The KO (DSS + Water) and KO (DSS + FMT) groups displayed indistinguishable body weight loss, colon length, DAI score, and histology score, which showed that FMT could not inhibit the disease in KO mice. In mice treated with FMT, the relative abundance of Akkermansia decreased, and Lactobacillus became dominant. In particular, compared with those in WT mice, the scores of DAI and colon histology were clearly decreased in the KO-DSS group. Microbiota structure showed a significant difference between KO and WT mice. Akkermansia were the dominant genus in healthy KO mice. The ineffectiveness of FMT in KO mice was related to the decreased abundance of Akkermansia. Gene Ontology enrichment analysis showed that differentially expressed genes between each group were mainly involved in cytoplasmic translation and cellular response to DNA damage stimulus. The top nine genes correlating with Akkermansia included Aqp4, Clca4a, Dpm3, Fau, Mcrip1, Meis3, Nupr1 L, Pank3, and Rps13 (|R| > 0.9, P < 0.01). CONCLUSION: FMT may ameliorate DSS-induced colitis by regulating the TLR4 signaling pathway. TLR4 modulates the composition of gut microbiota and the expression of related genes to ameliorate colitis and maintain the stability of the intestinal environment. Akkermansia bear great therapeutic potential for colitis.


Assuntos
Colite Ulcerativa , Colite , Receptor 4 Toll-Like , Animais , Camundongos , Colite/induzido quimicamente , Colite/terapia , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/genética , Colite Ulcerativa/terapia , Modelos Animais de Doenças , Transplante de Microbiota Fecal , Transdução de Sinais , Receptor 4 Toll-Like/genética
6.
Zhong Yao Cai ; 35(4): 648-50, 2012 Apr.
Artigo em Zh | MEDLINE | ID: mdl-23019915

RESUMO

OBJECTIVE: To optimize the extraction technology of total triterpenoids from Hypodematium sinense. METHODS: With 5% vanillin-glacial acetic acid solution and 72% sulfuric acid as chromogenic agent and the content of total tripenoids as index,using single factor experiment and orthogonal test,the optimal extraction condition was determined. RESULTS: The optimal conditions were solid-liquid ratio 1:12, 60% ethanol concentration, and ultrasonic extraction time of 60 min at 60 degrees C. CONCLUSION: The extraction technology is feasible and can be used as extraction process of total triterpenoids from Hypodematium sinense.


Assuntos
Gleiquênias/química , Tecnologia Farmacêutica/métodos , Triterpenos/isolamento & purificação , Ultrassom , Medicamentos de Ervas Chinesas/análise , Medicamentos de Ervas Chinesas/isolamento & purificação , Etanol/química , Componentes Aéreos da Planta/química , Solventes , Temperatura , Fatores de Tempo , Triterpenos/análise
7.
Gut Pathog ; 14(1): 41, 2022 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-36271438

RESUMO

BACKGROUND: The natural protoberberine jatrorrhizine (JA) is reported to have several medicinal properties and a significant effect on the gut microbiota of mice. The regulation of gut microbiota is generally known to play an important role in the intestinal mucosal immune response to ulcerative colitis (UC). However, whether JA can be used in the treatment of UC is still unclear. Our study aimed to investigate the underlying therapeutic effects and mechanisms of JA in treating colitis. RESULTS: Compared with the DSS-induced colitis model group, the JA + DSS treated group had more significant improvements in weight loss, disease activity index score, colon length shortening, and pathological inflammation. 16s rRNA sequencing analysis showed that JA treatment protected colitis mice against DSS-induced disturbance of gut microbiota. At the phylum level, reductions in Deferribacteres and Proteobacteria were observed in the JA-treated group; At the genus level, the JA-treated group showed an increased relative abundance of Akkermansia and decreased abundance of Escherichia-Shigella, Desulfovibrio, Mucispirillum, etc. Network pharmacology was then used to screen out five drug-disease target genes (NOS2, ESR1, CALM1, CALM2, CALM3). Transcriptomics analysis further validated that the NOS2 expression was significantly reduced in colon tissue of JA-administered mice compared with DSS control mice. Additionally, analysis of correlation suggested that NOS2 expression was negatively correlated with the relative abundance of AKKermansia and positively correlated with Desulfovibrio, Rikenella. CONCLUSION: JA alleviates ulcerative colitis via regulating gut microbiota and NOS2 expression.

8.
Microb Biotechnol ; 15(8): 2208-2222, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35439340

RESUMO

Cepharanthine (CEP) is an active alkaloid isolated from Stephania Cepharantha Hayata. It is reported that the anti-inflammatory properties of CEP could be employed to treat a variety of diseases. In this study, we first found that CEP ameliorates ulcerative colitis (UC) induced by DSS. The effect of CEP on gut microbiota was further evaluated by 16S rRNA gene sequencing, antibiotic pretreatment and faecal microbiota transplantation (FMT). Results showed that the abundances of gut microbiota, such as Romboutsia, Turicibacter and Escherichia-Shigella (especially Romboutsia), were significantly reduced after CEP treatment. Additionally, we explored the mechanisms of CEP by a strategy integrating transcriptomics with network pharmacology. The transcriptome data confirmed that CEP functioned through cytokine and cytokine receptor pathways. The expression levels of 10 pro-inflammatory hub genes (such as CXCL1, CXCL9, CCL7) were positively correlated with the abundance of Romboutsia. Our data identified Romboutsia as a potential pathobiont in UC. Collectively, we confirmed that CEP relieved colon inflammation by modulating gut microbiota and pro-inflammatory cytokine expression. CEP can be adopted to design novel effective therapeutic strategies for UC.


Assuntos
Colite Ulcerativa , Colite , Microbioma Gastrointestinal , Animais , Benzilisoquinolinas , Colite/tratamento farmacológico , Colite/terapia , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colo , Citocinas/metabolismo , Sulfato de Dextrana/efeitos adversos , Modelos Animais de Doenças , Camundongos , Camundongos Endogâmicos C57BL , RNA Ribossômico 16S/genética
9.
World J Gastroenterol ; 27(21): 2834-2849, 2021 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-34135557

RESUMO

BACKGROUND: Emerging evidence has demonstrated that fecal microbiota transplantation (FMT) has a promising therapeutic effect on mice with experimental colitis and patients with ulcerative colitis (UC), although the mechanism of FMT is unclear. AIM: To evaluate the protective effect of FMT on UC and clarify its potential dependence on the gut microbiota, through association analysis of gut microbiota with colon transcriptome in mice. METHODS: Dextran sodium sulfate (DSS)-induced experimental colitis was established and fecal microbiota was transplanted by gavage. Severity of colon inflammation was measured by body weight, disease activity index, colon length and histological score. Gut microbiota alteration was analyzed through 16S ribosomal ribonucleic acid sequencing. The differentially expressed genes (DEGs) in the colon were obtained by transcriptome sequencing. The activation status of colonic T lymphocytes in the lamina propria was evaluated by flow cytometry. RESULTS: Compared with the DSS group, the weight loss, colon length shortening and inflammation were significantly alleviated in the FMT group. The scores of disease activity index and colon histology decreased obviously after FMT. FMT restored the balance of gut microbiota, especially by upregulating the relative abundance of Lactobacillus and downregulating the relative abundance of Clostridium_sensu_stricto_1 and Turicibacter. In the transcriptomic analysis, 128 DEGs intersected after DSS treatment and FMT. Functional annotation analysis suggested that these DEGs were mainly involved in T-lymphocyte activation. In the DSS group, there was an increase in colonic T helper CD4+ and T cytotoxic CD8+ cells by flow cytometry. FMT selectively downregulated the ratio of colonic CD4+ and CD8+ T cells to maintain intestinal homeostasis. Furthermore, Clostri dium_sensu_stricto_1 was significantly related to inflammation-related genes including REG3G, CCL8 and IDO1. CONCLUSION: FMT ameliorated DSS-induced colitis in mice via regulating the gut microbiota and T-cell modulation.


Assuntos
Colite Ulcerativa , Colite , Microbioma Gastrointestinal , Animais , Linfócitos T CD8-Positivos , Colite/induzido quimicamente , Colite/terapia , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/terapia , Colo , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Transplante de Microbiota Fecal , Humanos , Camundongos
13.
Int J Infect Dis ; 25: 130-5, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24911886

RESUMO

OBJECTIVES: Antiretroviral therapy (ART) reduces the morbidity and mortality of patients infected with HIV. Standard ART includes either nevirapine or efavirenz, however the efficacy of these drugs is limited in patients receiving rifampin treatment for tuberculosis (TB). We compared the efficacy and safety of nevirapine- and efavirenz-based ART regimens in patients co-infected with both HIV and TB through a systematic review and meta-analysis. METHODS: A comprehensive search of the literature was carried out to identify clinical trials comparing the efficacy and safety of nevirapine- and efavirenz-based ART regimens in HIV-associated TB. Eligible clinical studies included at least one primary or secondary event; the primary event was virological response and secondary events were TB treatment outcomes, mortality, and safety profile. RESULTS: This meta-analysis compared five randomized clinical trials and four retrospective clinical trials. Both included patients co-infected with HIV and TB; 833 received nevirapine, while 1424 received efavirenz. The proportion of patients achieving a virological response by the end of the follow-up was higher in the efavirenz group: plasma viral load <400 copies/ml, risk ratio (RR) 1.10, 95% confidence interval (CI) 1.03-1.17 (p = 0.004); plasma viral load<50 copies/ml, RR 1.07, 95% CI 0.98-1.16 (p = 0.146). No significant differences were found in either mortality (RR 0.70, 95% CI 0.44-1.13, p = 0.142) or TB treatment outcomes (RR 1.01, 95% CI 0.96-1.06, p = 0.766). Due to adverse advents, nevirapine-based regimens significantly increased the risk of discontinuation of assigned ART (RR 0.43, 95% CI 0.23-0.81, p = 0.009). CONCLUSIONS: Although efavirenz-based ART was associated with more satisfactory virological outcomes, nevirapine-based ART could be considered an acceptable alternative for patients for whom efavirenz cannot be administered.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Benzoxazinas/uso terapêutico , Coinfecção , Infecções por HIV/tratamento farmacológico , Nevirapina/uso terapêutico , Alcinos , Fármacos Anti-HIV/efeitos adversos , Terapia Antirretroviral de Alta Atividade , Antituberculosos/uso terapêutico , Benzoxazinas/efeitos adversos , Contagem de Linfócito CD4 , Ensaios Clínicos como Assunto , Ciclopropanos , Infecções por HIV/imunologia , Infecções por HIV/mortalidade , Infecções por HIV/virologia , Humanos , Nevirapina/efeitos adversos , Rifampina/uso terapêutico , Resultado do Tratamento , Tuberculose/tratamento farmacológico , Carga Viral
14.
PLoS One ; 6(9): e23621, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21912640

RESUMO

BACKGROUND: The programmed cell death-1 receptor/programmed cell death-1 ligand (PD-1/PD-L1) pathway plays a crucial role in tumor evasion from host immunity. This study was designed to evaluate the association between circulating PD-L1/PD-1 and prognosis after cryoablation in patients with HBV-related hepatocellular carcinoma (HCC). METHODOLOGY/PRINCIPAL FINDINGS: In the present study, 141 HBV-related HCC patients were enrolled and of those 109 patients received cryoablation. Circulating PD-L1/PD-1 expression was tested by flow cytometry, and 23 patients were simultaneously evaluated for intratumoral PD-L1 expression by immunohistochemical staining. Circulating PD-1/PD-L1 expression was associated with severity of diseases in patients with HCC, and the circulating PD-L1 expression was closely correlated with intratumoral PD-L1 expression. Of the clinical parameters, PD-1/PD-L1 expression was associated with tumor size, blood vessel invasion and BCLC staging. Moreover, PD-1/PD-L1 expression dropped after cryoablation while being elevated at the time of tumor recurrence. Patients with higher expression of circulating PD-L1, as well as circulating PD-1, had a significantly shorter overall survival and tumor-free survival than those with lower expression. Multivariate analysis confirmed that circulating PD-L1 could serve as an independent predictor of overall survival and tumor-recurrence survival in HCC patients after cryoablation. CONCLUSIONS/SIGNIFICANCE: Upregulation of circulating PD-L1/PD-1 is associated with poor post-cryoablation prognosis in patients with HBV-related hepatocellular carcinoma.


Assuntos
Antígeno B7-H1/sangue , Carcinoma Hepatocelular/diagnóstico , Criocirurgia , Vírus da Hepatite B/fisiologia , Neoplasias Hepáticas/diagnóstico , Receptor de Morte Celular Programada 1/sangue , Regulação para Cima , Adulto , Idoso , Antígeno B7-H1/metabolismo , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/cirurgia , Carcinoma Hepatocelular/virologia , Progressão da Doença , Feminino , Humanos , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Receptor de Morte Celular Programada 1/metabolismo
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