Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 77
Filtrar
1.
Comput Intell Neurosci ; 2021: 7588221, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34603434

RESUMO

Reinforcement learning from demonstration (RLfD) is considered to be a promising approach to improve reinforcement learning (RL) by leveraging expert demonstrations as the additional decision-making guidance. However, most existing RLfD methods only regard demonstrations as low-level knowledge instances under a certain task. Demonstrations are generally used to either provide additional rewards or pretrain the neural network-based RL policy in a supervised manner, usually resulting in poor generalization capability and weak robustness performance. Considering that human knowledge is not only interpretable but also suitable for generalization, we propose to exploit the potential of demonstrations by extracting knowledge from them via Bayesian networks and develop a novel RLfD method called Reinforcement Learning from demonstration via Bayesian Network-based Knowledge (RLBNK). The proposed RLBNK method takes advantage of node influence with the Wasserstein distance metric (NIW) algorithm to obtain abstract concepts from demonstrations and then a Bayesian network conducts knowledge learning and inference based on the abstract data set, which will yield the coarse policy with corresponding confidence. Once the coarse policy's confidence is low, another RL-based refine module will further optimize and fine-tune the policy to form a (near) optimal hybrid policy. Experimental results show that the proposed RLBNK method improves the learning efficiency of corresponding baseline RL algorithms under both normal and sparse reward settings. Furthermore, we demonstrate that our RLBNK method delivers better generalization capability and robustness than baseline methods.


Assuntos
Reforço Psicológico , Recompensa , Algoritmos , Teorema de Bayes , Humanos , Bases de Conhecimento
2.
Trials ; 22(1): 545, 2021 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-34407832

RESUMO

BACKGROUND: Proton pump inhibitor (PPI) is effective for the treatment of nonerosive gastroesophageal reflux (NERD), but long-term use of PPI is prone to have complications and recurrence after withdrawal. Traditional Chinese medicine (TCM) can relieve the symptoms of reflux and improve the quality of life. The purpose of this study is to evaluate the safety and efficacy of Hewei Jiangni recipe (HWJNR) in the treatment of NERD with cold-heat complex syndrome, and clarify the mechanism of HWJNR on NERD based on the correlation analysis of intestinal flora and metabolites. METHODS: This is a single-center, randomized controlled, double-blind, placebo-controlled clinical trial in which 72 eligible participants with NERD and TCM syndrome of intermingled heat and cold will be randomly allocated in the ratio of 1:1 to two groups: TCM group and western medicine group. The TCM group will receive HWJNR with omeprazole enteric-coated tablets placebo, while the western medicine group will receive omeprazole enteric-coated tablets with HWJNR placebo. Each group will be treated for 8 weeks. The primary outcome is the score of gastroesophageal reflux disease (GERD) health-related quality of life questionnaire (GERD-Q). Secondary outcomes include SF-36 quality of life scale (SF-36), patient-reported outcomes (PRO) self-rating scale score, syndrome score of TCM, and adverse events. Mechanistic outcome is the correlation analysis of intestinal flora and metabolites from healthy individuals and NERD participants before and after the treatment respectively. DISCUSSION: The goal of this trial is to investigate the efficacy and safety of HWJNR in the treatment of NERD with cold-heat complex syndrome, and to study the composition structure and metabolite expression profile of intestinal flora in patients with NERD through 16SrRNA sequencing and metabolomic correlation analysis of fecal flora, which makes us identify the dominant links of treatment and reveal the potential mechanism of HWJNR. ChiCTR2000041225 . Registered on 22 December 2020.


Assuntos
Medicamentos de Ervas Chinesas , Qualidade de Vida , China , Método Duplo-Cego , Medicamentos de Ervas Chinesas/efeitos adversos , Temperatura Alta , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
3.
Cancer Med ; 10(19): 6795-6806, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34427987

RESUMO

The incidence and mortality of hepatocellular carcinoma (HCC) are gradually increasing during the past years. Recently, some studies have reported that malic enzyme (ME) plays an important role in cancer development, while the involvement of ME2 in HCC remains still undetermined. Here, we demonstrated that ME2 played an oncogenic role in HCC. ME2 was overexpressed in HCC tissues. TCGA database showed that the ME2 transcript level was inversely associated with the survival of HCC patients. Loss-of-function and gain-of-function assays showed that ME2 promoted HCC cell growth and migration. Furthermore, the xenografted tumorigenesis of MHCC97H cells was retarded by ME2 knockdown. ME2 silencing also suppressed the cell cycle process and induced apoptosis. Mechanistically, ME2 potentiated triglyceride synthesis, inhibition of which suppressed the proliferation and migration. We propose that ME2 promotes HCC progression by increasing triglyceride production.

4.
Turk J Gastroenterol ; 32(5): 422-430, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-34231471

RESUMO

BACKGROUND: This systematic review and meta-analysis were carried out on well-conducted and adequately powered studies to explore whether arterial stiffness was associated with inflammatory bowel disease (IBD). METHODS: The search for potential literature was conducted on PubMed, MEDLINE, Cochrane Library, and Embase from inception to February 15, 2020. The studies assessing arterial stiffness in IBD were reviewed and included. RESULTS: Conclusively, 17 eligible trials with a total of 2188 participants were in compliance with the inclusion criteria. Of the included 2188 participants, the cases for ulcerative colitis (UC) and Crohn's disease (CD) were 558 and 693, respectively. Altogether 10 studies were conducted to evaluate the carotid-femoral pulse wave velocity (CPWV) in overall IBD patients, which was significantly increased with the mean difference (MD) and 95% CI as 0.70 (0.48-0.92, P < .01). The pooled results for CPWV in patients with CD and UC were also faster than that of control groups with MD and 95% CI as 1.09 (0.45-1.72) and 0.57 (0.57-1.24), respectively. The CPWV in CD and UC groups was comparable with a MD of 0.07 (P = .74, 95% CI: -0.32 to 0.45). CONCLUSION: Arterial stiffness had associations with the overall IBD, UC, and CD with a similar strength of association between UC and CD.

5.
J Vasc Interv Radiol ; 32(8): 1194-1202, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33819601

RESUMO

PURPOSE: To evaluate the performance of the integrated liver inflammatory score (ILIS) in predicting survival in patients with hepatocellular carcinoma (HCC) who received transarterial chemoembolization, and to compare ILIS to other prognostic scoring systems and inflammatory indices. MATERIALS AND METHODS: This study included 192 patients with unresectable HCC who underwent transarterial chemoembolization from 3 medical centers. The potential risk factors of the patients' overall survival (OS) were determined by multivariate Cox regression analysis. The predictive performances of ILIS in 1-, 2-, 3-, 4-, and 5-year survival were evaluated using receiver operating characteristic curves. The discriminatory power in the OS of ILIS and the other known scoring systems or inflammatory indices was determined by C-statistic. RESULTS: Multivariate regression analysis showed that high ILIS (P = .047), low lymphocyte count (P = .034), beyond up-to-seven criteria (P = .021), and nonresponse to the first transarterial chemoembolization session (P = .039) were risk factors for poor prognosis after transarterial chemoembolization. The predictive performances of ILIS for 1-, 2-, 3-, 4-, and 5-year survival were good, with area under the curve values of 0.627, 0.631, 0.621, 0.577, and 0.681, respectively. ILIS outperformed other standard scoring systems and inflammatory indices in predicting OS, with a C-statistic of 0.625. CONCLUSIONS: ILIS is a powerful prognostic index for predicting the survival of patients with HCC after transarterial chemoembolization, which suggests that ILIS before treatment should be considered during the patient evaluation process.

6.
J Integr Med ; 19(3): 274-281, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33775600

RESUMO

OBJECTIVE: The clinical symptoms of diarrhea-predominant irritable bowel syndrome (IBS-D) can be effectively improved by traditional Chinese medicine (TCM) treatment, based on the usage of specific therapies for different TCM syndromes. However, in the stage of diagnosis, the standard criteria for the classification of TCM syndrome were still deficient. Through serum metabolic profiling, this study aimed to explore potential biomarkers in IBS-D patients with different TCM syndromes, which can assist in diagnosis of the disease. METHODS: Serum samples were collected from healthy controls (30 cases), IBS-D patients with Liver-Stagnation and Spleen-Deficiency syndrome (LSSD, 30 cases), Yang Deficiency of Spleen and Kidney syndrome (YDSK, 11 cases) and Damp Abundance due to Spleen-Deficiency syndrome (DASD, 22 cases). Serum metabolic profiling was conducted by ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. The potential biomarkers were screened by orthogonal partial least square-discriminate analysis, while metabolic pathways undergoing alterations were identified by pathway enrichment analysis in MetaboAnalyst 4.0. RESULTS: Overall, 34 potential biomarkers were identified in LSSD group, 36 in YDSK group and 31 in DASD group. And the 13 metabolites shared by three groups were determined as the potential biomarkers of IBS-D. Glycerophospholipid metabolism was disturbed significantly in IBS-D patients, which may play a role in IBS-D through inflammation. What's more, three TCM syndromes have the specific potential biomarkers in glycerophospholipid metabolism. CONCLUSION: The serum metabolomics revealed that different TCM syndrome types in IBS-D may have different metabolic patterns during disease progression and glycerophospholipid metabolism was one of the pathways, whose metabolism was disturbed differently among three TCM syndromes in IBS-D. Therefore, the specific potential biomarkers in glycerophospholipid metabolism of three TCM syndromes in IBS-D can serve as the objective indicators, which can facilitate the TCM-syndrome objective classification of IBS-D.

7.
PLoS One ; 16(1): e0245622, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33465129

RESUMO

The multi-energy conversion system (MCS) plays an important role in improving the utilization of energy resources and realizing the energy transition. With the application of the new generation of information technologies, the new MCS can realize real-time information interaction, multi-energy collaboration, and real-time demand response, in which energy suppliers can intelligently motivate consumers' energy use behavior. In this paper, an MCS coupled with a cloud platform is proposed to address information explosion and data security issues. Due to the development of Internet technology, the increasing energy data, and the serious energy coupling, it is difficult for traditional optimization methods to deal with the interaction between participants of the MCS. Therefore, the non-cooperative game is used to formulate the interactions between participants with the aim of maximizing the energy suppliers' profit and minimizing the customers' cost. It is proved that the game model is an ordinary game with one Nash equilibrium. The simulation was performed with a gradient projection algorithm and the results show that the proposed MCS improves energy utilization efficiency through energy conversion while ensuring consumer satisfaction, and benefits both the customers and suppliers by reducing the energy consumption cost and the peak load demand, which effectively improve the supply quality and enrich the energy consumption patterns.


Assuntos
Economia/estatística & dados numéricos , Teoria do Jogo , Indústrias/métodos , Disseminação de Informação/métodos , Algoritmos , Segurança Computacional , Simulação por Computador , Comportamento do Consumidor/estatística & dados numéricos , Fontes de Energia Elétrica/estatística & dados numéricos , Eletricidade , Modelos Teóricos
8.
Dig Dis Sci ; 66(1): 19-28, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32095968

RESUMO

BACKGROUND: Gastroesophageal reflux disease (GERD) is a common disorder, and is typically treated with proton-pump inhibitors (PPIs) as the recommended first-line therapy. Recently, a new potassium-competitive acid blocker, vonoprazan, was launched in Japan. It is uncertain whether the standard dose of vonoprazan 20 mg is superior to that of PPIs for GERD, so a direct comparison of the therapeutic effects and adverse events between vonoprazan 20 mg and PPIs is needed. METHODS: MEDLINE, the Cochrane Central Register of Controlled Trials, and Embase were chosen as the literature sources. Randomized controlled trials for vonoprazan 20 mg and PPIs published in English were searched. Data from studies meeting the eligibility criteria were extracted individually by two researchers and compared to maintain consistency. RESULTS: Fifty-six articles were identified in the databases, and one study was manually searched and added to the analysis, ultimately yielding six eligible studies. For the main analysis, the risk ratios (RR) of efficacy and adverse events between vonoprazan and PPIs were 1.06 (0.99-1.13) and 1.08 (0.96-1.22), respectively. Subgroup analysis for patients with severe esophagitis at baseline showed significantly higher results for vonoprazan than lansoprazole, with an RR of 1.14 (1.06-1.22). CONCLUSIONS: Our findings suggest that vonoprazan is non-inferior to PPIs as therapy for patients with GERD. Subgroup analysis indicates that vonoprazan is more effective than PPIs for patients with severe erosive esophagitis. The safety outcomes for vonoprazan are similar to those for PPIs.


Assuntos
Refluxo Gastroesofágico/diagnóstico , Refluxo Gastroesofágico/tratamento farmacológico , Inibidores da Bomba de Prótons/uso terapêutico , Pirróis/uso terapêutico , Sulfonamidas/uso terapêutico , Refluxo Gastroesofágico/complicações , Azia/diagnóstico , Azia/tratamento farmacológico , Azia/etiologia , Humanos , Inibidores da Bomba de Prótons/efeitos adversos , Pirróis/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Sulfonamidas/efeitos adversos , Resultado do Tratamento
9.
Dig Liver Dis ; 53(5): 566-573, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33339748

RESUMO

BACKGROUND: Side effects of long-term acid suppression have increased the scholars' interest in nonpharmacologic intervention. AIMS: We summarized an umbrella review of the association between environmental factors and gastroesophageal reflux disease (GERD) and assessed their credibility. METHODS: We appraised systematic reviews and meta-analyses. For each meta-analysis, we considered the effect size, 95% confidence interval, the heterogeneity, small-study effects, P-value for excess significance and largest study significant, then we graded the evidence according to Assessment of Multiple Systematic Reviews and the GRADE assessment. RESULTS: 23 publications met the inclusion criteria (13 meta-analyses and 10 systematic reviews), which evaluated 24 environmental factors. Among observational studies, we identified 7 risk factors: overweight/obesity [GERD/erosive esophagitis (EE)/GERD symptom], central adiposity [EE], smoking [GERD], alcohol [GERD/EE/non-erosive reflux disease (NERD)], NSAID [GERD], coffee [EE], Helicobacter pylori eradication [EE], and 1 protective factor: physical activity [GERD], this was based on a suggestive evidence of credibility. Across intervention studies, we identified 1 risk factor-Helicobacter pylori eradication [GERD] and 1 protective factor-breathing exercises [GERD], evidence for both was low grade. CONCLUSIONS: We found varying levels of evidence for different environmental factors of GERD. None of them was proven to be convincing or highly recommended.

10.
Artigo em Inglês | MEDLINE | ID: mdl-33281910

RESUMO

Aim: This study aims to uncover the pharmacological mechanism of Tongxie Anchang Decoction (TXACD), a new and effective traditional Chinese medicine (TCM) prescription, for treating irritable bowel syndrome with diarrhea predominant (IBS-D) using network pharmacology. Methods: The active compounds and putative targets of TXACD were retrieved from TCMSP database and published literature; related target genes of IBS-D were retrieved from GeneCards; PPI network of the common target hub gene was constructed by STRING. Furthermore, these hub genes were analyzed using gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Results: A total of 54 active compounds and 639 targets were identified through a database search. The compound-target network was constructed, and the key compounds were screened out according to the degree. By using the PPI and GO and KEGG enrichment analyses, the pharmacological mechanism network of TXACD in the treatment of IBS-D was constructed. Conclusions: This study revealed the possible mechanisms by which TXACD treatment alleviated IBS-D involvement in the modulation of multiple targets and multiple pathways, including the immune regulation, inflammatory response, and oxidative stress. These findings provide novel insights into the regulatory role of TXACD in the prevention and treatment of IBS-D and hold promise for herb-based complementary and alternative therapy.

11.
Medicine (Baltimore) ; 99(52): e23868, 2020 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-33350782

RESUMO

BACKGROUND: Diarrhea-predominant irritable bowel syndrome (IBS-D) is a kind of functional gastrointestinal disorder with obscure pathogenesis, and exploration about differential gene expression and cell heterogeneity of T lymphocytes in peripheral blood in IBS-D patients still remains unknown. Clinicians tend to use symptomatic treatment, but the efficacy is unstable and symptoms are prone to relapse. Traditional Chinese Medicine (TCM) is used frequently in IBS-D with stable and lower adverse effects. Tong-Xie-An-Chang Decoction (TXACD) has been proven to be effective in the treatment of IBS-D. However, the underlying therapeutic mechanism remains unclear. This trial aims to evaluate the clinical efficacy and safety of TXACD in IBS-D and elucidate the gene-level mechanism of IBS-D and therapeutic targets of TXACD based on single-cell sequencing technology. METHODS/DESIGN: This is a randomized controlled, double-blind, double-simulation clinical trial in which 72 eligible participants with IBS-D and TCM syndrome of liver depression and spleen deficiency will be randomly allocated in the ratio of 1:1 to two groups: the experimental group and the control group. The experimental group receives Tong-Xie-An-Chang Decoction (TXACD) and Pinaverium bromide tablets placebo; the control group receives pinaverium bromide tablets and TXACD placebo. Each group will be treated for 4 weeks. The primary outcome: the rate of IBS-Symptom Severity Score (IBS-SSS). The secondary outcomes: TCM syndrome score, adequate relief and IBS-Quality of Life Questionnaire (IBS-QOL). Mechanistic outcome is the single-cell sequencing profiling of the T lymphocytes in peripheral blood from IBS-D participants before and after the treatment and healthy individuals. DISCUSSION: This trial will prove the efficacy and safety of TXACD with high-quality evidence and provide a comprehensive perspective on the molecular mechanism of IBS-D by single-cell sequencing profiling, which makes us pinpoint specific biomarkers of IBS-D and therapeutic targets of TXACD.


Assuntos
Diarreia , Medicamentos de Ervas Chinesas , Síndrome do Intestino Irritável , Qualidade de Vida , Adulto , Misturas Complexas/administração & dosagem , Misturas Complexas/efeitos adversos , Diarreia/tratamento farmacológico , Diarreia/etiologia , Diarreia/psicologia , Método Duplo-Cego , Monitoramento de Medicamentos/métodos , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/efeitos adversos , Feminino , Perfilação da Expressão Gênica/métodos , Humanos , Síndrome do Intestino Irritável/sangue , Síndrome do Intestino Irritável/complicações , Síndrome do Intestino Irritável/tratamento farmacológico , Síndrome do Intestino Irritável/fisiopatologia , Masculino , Medicina Tradicional Chinesa/métodos , Extratos Vegetais/administração & dosagem , Extratos Vegetais/efeitos adversos , Avaliação de Sintomas , Linfócitos T , Resultado do Tratamento
12.
Medicine (Baltimore) ; 99(51): e23806, 2020 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-33371156

RESUMO

BACKGROUND: Functional constipation (FC) is a common gastrointestinal disorder characterized by slow bowel movement and defecation difficulties, significantly impacting patients' quality of life and exerting heavy financial burden to whole society. However, more than 50% FC patients are not completely satisfied with current therapies and alternative therapies are urgently required. Increasing evidences have demonstrated that traditional Chinese medicine has a good therapeutic effect on FC, which is well known for its multitarget and multimode effects on diverse diseases as well as less side effects. Furthermore, studies proved that Qi Di Laxative Decoction was an effective treatment for FC. Its safety and effectiveness should be verified by further studies. METHODS: We will search the following electronic databases for randomized controlled trials to evaluate the clinical efficacy of Qi Di Laxative Decoction in treating FC: Wanfang and Pubmed Database, China National Knowledge Infrastructure Database, Cochrane Central Register of Controlled Trials, Cumulative Index of Nursing and Allied Health Literature, and Excerpta Medica database. Each database will be searched from inception to November 2020. The entire process will include study selection, data extraction, risk of bias assessment, and meta-analyses. RESULTS: This proposed study will evaluate the clinical efficacy of Qi Di Laxative Decoction for patients with FC. The outcomes will include changes in FC relief and adverse effect. CONCLUSION: This proposed systematic review will evaluate the existing evidence on the clinical efficacy of Qi Di Laxative Decoction in treating FC. DISSEMINATION AND ETHICS: The results of this review will be disseminated through peer-reviewed publication. Because all of the data used in this systematic review and meta-analysis has been published, this review does not require ethical approval. Furthermore, all data will be analyzed anonymously during the review process. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/M2ESR.


Assuntos
Protocolos Clínicos , Constipação Intestinal/tratamento farmacológico , Laxantes/normas , Medicina Tradicional Chinesa/normas , Humanos , Laxantes/uso terapêutico , Medicina Tradicional Chinesa/métodos , Metanálise como Assunto , Revisões Sistemáticas como Assunto , Resultado do Tratamento
13.
World J Gastroenterol ; 26(39): 5983-5996, 2020 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-33132649

RESUMO

BACKGROUND: Ulcerative colitis (UC) is an inflammatory bowel disease that is difficult to diagnose and treat. To date, the degree of inflammation in patients with UC has mainly been determined by measuring the levels of nonspecific indicators, such as C-reactive protein and the erythrocyte sedimentation rate, but these indicators have an unsatisfactory specificity. In this study, we performed bioinformatics analysis using data from the National Center for Biotechnology Information-Gene Expression Omnibus (NCBI-GEO) databases and verified the selected core genes in a mouse model of dextran sulfate sodium (DSS)-induced colitis. AIM: To identify UC-related differentially expressed genes (DEGs) using a bioinformatics analysis and verify them in vivo and to identify novel biomarkers and the underlying mechanisms of UC. METHODS: Two microarray datasets from the NCBI-GEO database were used, and DEGs between patients with UC and healthy controls were analyzed using GEO2R and Venn diagrams. We annotated these genes based on their functions and signaling pathways, and then protein-protein interactions (PPIs) were identified using the Search Tool for the Retrieval of Interacting Genes. The data were further analyzed with Cytoscape software and the Molecular Complex Detection (MCODE) app. The core genes were selected and a Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis was performed. Finally, colitis model mice were established by administering DSS, and the top three core genes were verified in colitis mice using real-time polymerase chain reaction (PCR). RESULTS: One hundred and seventy-seven DEGs, 118 upregulated and 59 downregulated, were initially identified from the GEO2R analysis and predominantly participated in inflammation-related pathways. Seven clusters with close interactions in UC formed: Seventeen core genes were upregulated [C-X-C motif chemokine ligand 13 (CXCL13), C-X-C motif chemokine receptor 2 (CXCR2), CXCL9, CXCL5, C-C motif chemokine ligand 18, interleukin 1 beta, matrix metallopeptidase 9, CXCL3, formyl peptide receptor 1, complement component 3, CXCL8, CXCL1, CXCL10, CXCL2, CXCL6, CXCL11 and hydroxycarboxylic acid receptor 3] and one was downregulated [neuropeptide Y receptor Y1 (NYP1R)] in the top cluster according to the PPI and MCODE analyses. These genes were substantially enriched in the cytokine-cytokine receptor interaction and chemokine signaling pathways. The top three core genes (CXCL13, NYP1R, and CXCR2) were selected and verified in a mouse model of colitis using real-time PCR Increased expression was observed compared with the control mice, but only CXCR2 expression was significantly different. CONCLUSION: Core DEGs identified in UC are related to inflammation and immunity inflammation, indicating that these reactions are core features of the pathogenesis of UC. CXCR2 may reflect the degree of inflammation in patients with UC.


Assuntos
Colite Ulcerativa , Colite , Animais , Colite/induzido quimicamente , Colite/genética , Colite Ulcerativa/genética , Biologia Computacional , Perfilação da Expressão Gênica , Humanos , Camundongos , Software
14.
Mol Cell ; 80(4): 607-620.e12, 2020 11 19.
Artigo em Inglês | MEDLINE | ID: mdl-33113344

RESUMO

Aberrant mitophagy has been implicated in a broad spectrum of disorders. PINK1, Parkin, and ubiquitin have pivotal roles in priming mitophagy. However, the entire regulatory landscape and the precise control mechanisms of mitophagy remain to be elucidated. Here, we uncover fundamental mitophagy regulation involving PINK1 and a non-canonical role of the mitochondrial Tu translation elongation factor (TUFm). The mitochondrion-cytosol dual-localized TUFm interacts with PINK1 biochemically and genetically, which is an evolutionarily conserved Parkin-independent route toward mitophagy. A PINK1-dependent TUFm phosphoswitch at Ser222 determines conversion from activating to suppressing mitophagy. PINK1 modulates differential translocation of TUFm because p-S222-TUFm is restricted predominantly to the cytosol, where it inhibits mitophagy by impeding Atg5-Atg12 formation. The self-antagonizing feature of PINK1/TUFm is critical for the robustness of mitophagy regulation, achieved by the unique kinetic parameters of p-S222-TUFm, p-S65-ubiquitin, and their common kinase PINK1. Our findings provide new mechanistic insights into mitophagy and mitophagy-associated disorders.


Assuntos
Drosophila melanogaster/crescimento & desenvolvimento , Mitocôndrias/patologia , Proteínas Mitocondriais/metabolismo , Mitofagia , Fator Tu de Elongação de Peptídeos/metabolismo , Proteínas Quinases/metabolismo , Animais , Citosol/metabolismo , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Feminino , Células HeLa , Humanos , Masculino , Mitocôndrias/genética , Mitocôndrias/metabolismo , Proteínas Mitocondriais/genética , Fator Tu de Elongação de Peptídeos/genética , Fosforilação , Domínios e Motivos de Interação entre Proteínas , Proteínas Quinases/genética , Transporte Proteico , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo
15.
Medicine (Baltimore) ; 99(35): e21903, 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32871923

RESUMO

INTRODUCTION: Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) characterized by a relapsing-remitting course owing to recurrent intestinal inflammation. UC often has symptoms such as intermittent rectal bleeding, diarrhea, and abdominal pain. As the precise etiology of UC has not completely clarified, UC has become a public health challenge worldwide. According to an epidemiological survey, there were about 350,000 new cases of IBD in China from 2005 to 2014. By 2025, the number of IBD patients in China will reach 1.5 million. Traditional Chinese medicine (TCM) has been widely used to treat UC in China, however, it is still challenging to systematically determine the efficacy of in UC. Therefore, this trial aims to evaluate the clinical efficacy and safety of CHM in the treatment of mild active UC patients. METHODS: A multi-center, double-blinding, double-dummy, active-controlled, randomized trial will be established. A total of 240 patients in 6 centers with mild active UC (Mayo score is 3-5 points) and TCM syndrome of damp-heat stasis blocking and spleen-qi deficiency will be randomly allocated in the ratio of 1:1 to 2 groups: the experimental group and the control group. The experimental group will receive Hudi enteric-coated capsules (HEC) and enteric-coated mesalazine tablets placebo; the control group will receive enteric-coated mesalazine tablets and HEC placebo. Each group will be treated for 8 weeks. The primary therapeutic outcome: the rate of clinical efficacy and clinical remission at 8 weeks of treatment (last survey point) according to the modified Mayo score. The secondary outcomes: individual symptom score, TCM syndrome score, endoscopic response rate, mucosal healing rate, and quality of life scale score. Outcomes will be assessed at baseline and the end of the trial. Besides, intestinal mucosa, stools and blood biopsies from the mild active UC patients before and after treatment will be collected to reveal the underlying mechanisms. DISCUSSION: The results of this trial will provide compelling evidence of the efficacy and safety of HEC for treatment of mild active UC and preliminarily show the potential mechanism of how HEC acts. Finally, it will widen treatment options for patients with mild active UC.


Assuntos
Colite Ulcerativa/terapia , Medicina Tradicional Chinesa , Método Duplo-Cego , Humanos , Medicina Tradicional Chinesa/efeitos adversos , Resultado do Tratamento
16.
World J Gastroenterol ; 26(28): 4170-4181, 2020 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-32821078

RESUMO

BACKGROUND: Recent research suggests that although prokinetic agents, acid suppressors, and radical treatment for Helicobacter pylori infection may be effective in patients with functional dyspepsia (FD), a large proportion of patients still fail to respond to these treatments or may suffer from severe adverse reactions. Many traditional Chinese medicinal herbs can regulate the status of the entire body and have special advantages in the treatment of functional diseases. The present study was designed to verify the efficacy of Biling Weitong Granules (BLWTG), a traditional Chinese medicinal herbal compound formula, in alleviating epigastric pain syndrome (EPS) in FD patients, in an attempt to provide an effective prescription for the clinical treatment of this disease. AIM: To evaluate the clinical efficacy and safety of BLWTG in treating EPS in patients with FD. METHODS: In this multicenter, stratified, randomized, double-blind, placebo-controlled, parallel group clinical trial, eligible patients were randomized into the BLWTG and placebo groups who were treated for 6 wk. Efficacy indicators including the severity and frequency of EPS and the time to pain resolution and safety indicators including adverse events were observed and compared. RESULTS: The baseline demographic data and clinical characteristics, such as epigastric pain symptoms, pain intensity, and frequency of attacks, were matched between the two groups before randomization. After 6 wk of treatment and after the center effect was eliminated, the epigastric pain was significantly improved in 28.33% and 85.59% of the patients in the placebo and BLWTG groups, respectively (P < 0.05). At 6 wk, the resolution rate of epigastric pain was 15% and 69.49% in the placebo and BLWTG groups, respectively (P < 0.05). The differences of total FD clinical score between these two groups were significant (P < 0.05) at 2, 4, and 6 wk (P < 0.05). The scores of each item and the total score in the Functional Digestive Disorders Quality of Life Questionnaire showed significant differences between the two groups at 6 wk after both the center and interaction effects were eliminated (P < 0.05). There was no significant difference in the incidence of adverse events between the two groups, and no serious adverse event was noted during the observation. CONCLUSION: Compared with placebo, BLWTG markedly improved EPS in FD patients without causing serious adverse reactions.


Assuntos
Dispepsia , Infecções por Helicobacter , Helicobacter pylori , Método Duplo-Cego , Dispepsia/tratamento farmacológico , Humanos , Medicina Tradicional Chinesa , Qualidade de Vida , Resultado do Tratamento
17.
Front Microbiol ; 11: 731, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32425906

RESUMO

Ulcerative colitis is a gastrointestinal disorder intricately associated with intestinal dysbiosis, but effective treatments are currently limited. Indigo naturalis, a traditional Chinese medicine derived from indigo plants, has been widely used in the treatment of ulcerative colitis. However, the specific mechanisms have not yet been identified. Accordingly, in this study, we evaluated the effects and mechanisms of indigo naturalis on dextran sulfate sodium (DSS)-induced colitis in rats. Our results showed that indigo naturalis potently alleviated DSS-induced colitis in rats, and reversed DSS-induced intestinal dysbiosis using bacterial 16S rRNA amplicon sequencing. The protective effects of indigo naturalis were gut microbiota dependent, as demonstrated by antibiotic treatments and fecal microbiota transplantation. Depletion of the gut microbiota through a combination of antibiotic treatments blocked the anti-inflammatory effect of indigo naturalis on the DSS-induced colitis, and the recipients of the gut microbiota from indigo naturalis-treated rats displayed a significantly attenuated intestinal inflammation, which was actively responsive to therapeutic interventions with indigo naturalis. Notably, supplement with indigo naturalis greatly increased the levels of feces butyrate, which was positively correlated with the relative abundances of Ruminococcus_1 and Butyricicoccus. We further showed that indigo naturalis-dependent attenuation of colitis was associated with elevated expression of short-chain fatty acid-associated receptors GPR41 and GPR43. Collectively, these results suggested that indigo naturalis alleviates DSS-induced colitis in rats through a mechanism of the microbiota-butyrate axis, particularly alterations in Ruminococcus_1 and Butyricicoccus abundances, and target-specific microbial species may have unique therapeutic promise for ulcerative colitis.

18.
Mediators Inflamm ; 2019: 4038619, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31814801

RESUMO

Anemia is one of the most common complications in patients with inflammatory bowel disease (IBD). Hepcidin as a key regulator of iron metabolism is pivotal in mediating the occurrence of anemia of chronic disease. Herein, we analyzed the levels of hepcidin in sera from IBD patients by enzyme-linked immunosorbent assay and investigated its potential role in regulating the anemia in IBD. We observed that the levels of serum hepcidin were increased in active IBD patients compared with those in remitted IBD patients and healthy controls and that serum hepcidin was associated with disease activity, CRP, and ESR, respectively. Importantly, we found that the increased levels of serum hepcidin were positively correlated with the severity of anemia and the imbalance of iron metabolism in anemic UC and CD patients. Proinflammatory factors (e.g., IL-6, IL-17, and TNF-α) were positively correlated with the concentrations of serum hepcidin in IBD patients. Interestingly, hepcidin was found to be decreased in patients with Crohn's disease after successful therapy with anti-TNF-α mAb (i.e., infliximab), indicating the underlying association between TNF-α and hepcidin expression. To investigate the specific mechanisms involved, we cultured LO2 and HepG2 cell lines in vitro under stimulation with TNF-α and observed that the levels of hepcidin mRNA were markedly upregulated in caspase-3/8- and NF-κB-dependent manners. Therefore, our data suggest that TNF-α stimulates the expression of hepcidin in IBD patients, resulting in aggravated anemia and that blockage of TNF-α or the caspase-3/8 and NF-κB pathways could downregulate hepcidin expression. This study provides inspiration for the therapy and management of anemia in IBD.


Assuntos
Anemia/tratamento farmacológico , Anemia/metabolismo , Anticorpos Monoclonais/uso terapêutico , Hepcidinas/metabolismo , Doenças Inflamatórias Intestinais/tratamento farmacológico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adolescente , Adulto , Idoso , Anemia/imunologia , Anticorpos Monoclonais/imunologia , Proteína C-Reativa/metabolismo , Caspase 3/metabolismo , Caspase 8/metabolismo , Criança , Doença de Crohn/tratamento farmacológico , Doença de Crohn/imunologia , Doença de Crohn/metabolismo , Feminino , Células Hep G2 , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Hepcidinas/genética , Humanos , Doenças Inflamatórias Intestinais/imunologia , Doenças Inflamatórias Intestinais/metabolismo , Interleucina-17/metabolismo , Interleucina-6 , Masculino , Pessoa de Meia-Idade , NF-kappa B/metabolismo , RNA Mensageiro/metabolismo , Fator de Necrose Tumoral alfa/imunologia , Adulto Jovem
19.
Sci Total Environ ; 694: 133742, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31756833

RESUMO

Urban heat island (UHI) effect has serious negative impacts on urban ecosystems and human well-being. Mitigation of UHI using nature-based solutions is highly desirable. It was well known that urban green infrastructure (UGI), i.e., urban vegetation, can effectively mitigate UHI effect. However, the potential of urban blue infrastructure (UBI), i.e., urban surface water, on UHI mitigation is not well understood, although its potential to lower UHI effect via evaporation is similar to the biophysical mechanism of evapotranspiration through vegetation. In this paper, we study the relationship between UBI and land surface temperature (LST) in Wuhan city in central China, using a normalized difference water index (NDWI), maximum local cool island intensity and the maximum cooling distance as indicators for the cooling effects of UBI, respectively. We found a significant negative linear relationship between mean LST and NDWI after NDWI passes a critical threshold value. NDWI is an effective biophysical parameter to delineate the spatial distribution of UBI. The cooling effects of UBI are influenced both by its size and shape. Water surface temperature decreased logarithmically with increasing UBI size, critical threshold values of UBI size corresponding to maximum cooling efficiency do exists. Maximum cooling distance and maximum local cool island intensity are also affected by the shape and size of UBI, and exhibit seasonal and spatial variations. These results provide insights for urban landscape planning regarding how to use UBI as a nature-based solution to improve urban thermal environment.

20.
Ying Yong Sheng Tai Xue Bao ; 30(10): 3403-3410, 2019 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-31621226

RESUMO

Residential area, usually consisting of buildings and vegetation, is one of the dominant land use types and an important kind of habitat in the urban area. Therefore, it plays an important role in urban biodiversity conservation. Previous studies found that plant diversity abroad in urban residential areas was influenced by socioeconomic factors. However, it is not clear whether this result hold for Chinese cities which have completely different urban management regime. In this study, we investigated plant species diversity in 39 residential neighborhoods in Shanghai. Biodiversity indexes, regression analysis, and partial least square regression analysis were employed to estimate the relationships between plant diversity and socioeconomic factors of population density, house price, house age and greenspace coverage. Our results showed that socioeconomic factors did affect plant diversity in urban residential areas in Shanghai. The effects varied with plant species, population density, house price, house age, and greenspace coverage. The house age had the strongest effect on most plant taxa, then followed by population density, house price, and greenspace coverage. We tested the hypotheses of "luxury effect" and "legacy effect", and found that they only partially explained the spatial distribution of plant taxa in Shanghai. These results could provide insights for management and conservation of plant diversity, as well as urban landscape planning and design in Shanghai.


Assuntos
Biodiversidade , Plantas , China , Cidades , Fatores Socioeconômicos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...