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1.
World J Gastroenterol ; 27(31): 5232-5246, 2021 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-34497447

RESUMO

BACKGROUND: Artificial intelligence in colonoscopy is an emerging field, and its application may help colonoscopists improve inspection quality and reduce the rate of missed polyps and adenomas. Several deep learning-based computer-assisted detection (CADe) techniques were established from small single-center datasets, and unrepresentative learning materials might confine their application and generalization in wide practice. Although CADes have been reported to identify polyps in colonoscopic images and videos in real time, their diagnostic performance deserves to be further validated in clinical practice. AIM: To train and test a CADe based on multicenter high-quality images of polyps and preliminarily validate it in clinical colonoscopies. METHODS: With high-quality screening and labeling from 55 qualified colonoscopists, a dataset consisting of over 71000 images from 20 centers was used to train and test a deep learning-based CADe. In addition, the real-time diagnostic performance of CADe was tested frame by frame in 47 unaltered full-ranged videos that contained 86 histologically confirmed polyps. Finally, we conducted a self-controlled observational study to validate the diagnostic performance of CADe in real-world colonoscopy with the main outcome measure of polyps per colonoscopy in Changhai Hospital. RESULTS: The CADe was able to identify polyps in the test dataset with 95.0% sensitivity and 99.1% specificity. For colonoscopy videos, all 86 polyps were detected with 92.2% sensitivity and 93.6% specificity in frame-by-frame analysis. In the prospective validation, the sensitivity of CAD in identifying polyps was 98.4% (185/188). Folds, reflections of light and fecal fluid were the main causes of false positives in both the test dataset and clinical colonoscopies. Colonoscopists can detect more polyps (0.90 vs 0.82, P < 0.001) and adenomas (0.32 vs 0.30, P = 0.045) with the aid of CADe, particularly polyps < 5 mm and flat polyps (0.65 vs 0.57, P < 0.001; 0.74 vs 0.67, P = 0.001, respectively). However, high efficacy is not realized in colonoscopies with inadequate bowel preparation and withdrawal time (P = 0.32; P = 0.16, respectively). CONCLUSION: CADe is feasible in the clinical setting and might help endoscopists detect more polyps and adenomas, and further confirmation is warranted.


Assuntos
Pólipos do Colo , Aprendizado Profundo , Inteligência Artificial , Pólipos do Colo/diagnóstico por imagem , Colonoscopia , Computadores , Humanos
2.
Zhongguo Zhong Yao Za Zhi ; 46(14): 3633-3642, 2021 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-34402287

RESUMO

This article is to explore the antidepressant mechanism of Shugan Lipi recipe in regulating tryptophan metabolism,and to find out their common pharmacodynamic substances. UPLC-Q-TOF-MS technology was used to establish fingerprints of Shugan Lipi recipe,and 124 components were identified. The depressed mouse model was replicated by triple-one multiple stress method. Chaihu Shugan Powder,Sini Powder and Xiaoyao Powder were administered in groups to observe the changes in body weight and behavior of the mice. The results showed that compared with the model group,the body weight,sucrose preference percentage and autonomous activity behavior of each administration group were improved. Among them,the effect of Chaihu Shugan Powder was better than that of Sini Powder and Xiaoyao Powder. LC-MS/MS method was used to determine the contents of 5-hydroxytryptamine( 5-HT),kynurenine( KYN) and tryptophan( TPP) in blood,liver,brain,colon and other tissues,as well as TDO enzyme activity in liver. Western blot and RT-PCR were used to detect the protein and gene expression of TDO enzyme,respectively. It was found that the three prescriptions increased the ratio of 5-HT/KYN in different degrees,decreased the ratio of KYN/TRP in liver,colon and brain,and decreased the expression level and activity of TDO enzyme in liver. The order of their ability to regulate tryptophan metabolism was Chaihu Shugan Powder>Sini Powder>Xiaoyao Powder. In addition,the correlation between the chromatographic peaks in the fingerprints of Shugan Lipi recipes and the pharmacodynamic indexes of tryptophan metabolism was analyzed by the grey relation analysis. The grey relation analysis found that the chemical components with the highest correlation with tryptophan metabolism were mainly from Paeoniae Radix Alba,Citri Reticulatae Pericarpium,Aurantii Fructus Immaturus and Aurantii Fructus. UPLC-Q-TOF-MS was used to analyze the migration components in the plasma of mice after administration of Shugan Lipi recipe,and to verify the common pharmacodynamic substances of Shugan Lipi recipe. The migration of these detected components in plasma was studied,and a total of 18 prototype components and 36 metabolites were identified. Therefore,it was believed that Chaihu Shugan Powder,Sini Powder and Xiaoyao Powder could play an antidepressant role by reducing the expression of TDO enzyme in the liver and regulating the metabolism of tryptophan.The components contained in Paeoniae Radix Alba,Citri Reticulatae Pericarpium,Aurantii Fructus Immaturus and Aurantii Fructus were the common pharmacodynamic substances of Shugan Lipi recipe,which played an important role in regulating tryptophan metabolism.


Assuntos
Paeonia , Triptofano , Animais , Antidepressivos , Cromatografia Líquida , Camundongos , Espectrometria de Massas em Tandem
3.
World J Gastroenterol ; 27(28): 4667-4686, 2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34366628

RESUMO

BACKGROUND: Sorafenib is the first-line treatment for patients with advanced hepatocellular carcinoma (HCC). Y-box binding protein 1 (YB-1) is closely correlated with tumors and drug resistance. However, the relationship between YB-1 and sorafenib resistance and the underlying mechanism in HCC remain unknown. AIM: To explore the role and related mechanisms of YB-1 in mediating sorafenib resistance in HCC. METHODS: The protein expression levels of YB-1 were assessed in human HCC tissues and adjacent nontumor tissues. Next, we constructed YB-1 overexpression and knockdown hepatocarcinoma cell lines with lentiviruses and stimulated these cell lines with different concentrations of sorafenib. Then, we detected the proliferation and apoptosis in these cells by terminal deoxynucleotidyl transferase dUTP nick end labeling, flow cytometry and Western blotting assays. We also constructed a xenograft tumor model to explore the effect of YB-1 on the efficacy of sorafenib in vivo. Moreover, we studied and verified the specific molecular mechanism of YB-1 mediating sorafenib resistance in hepatoma cells by digital gene expression sequencing (DGE-seq). RESULTS: YB-1 protein levels were found to be higher in HCC tissues than in corresponding nontumor tissues. YB-1 suppressed the effect of sorafenib on cell proliferation and apoptosis. Consistently, the efficacy of sorafenib in vivo was enhanced after YB-1 was knocked down. Furthermore, KEGG pathway enrichment analysis of DGE-seq demonstrated that the phosphoinositide-3-kinase (PI3K)/protein kinase B (Akt) signaling pathway was essential for the sorafenib resistance induced by YB-1. Subsequently, YB-1 interacted with two key proteins of the PI3K/Akt signaling pathway (Akt1 and PIK3R1) as shown by searching the BioGRID and HitPredict websites. Finally, YB-1 suppressed the inactivation of the PI3K/Akt signaling pathway induced by sorafenib, and the blockade of the PI3K/Akt signaling pathway by LY294002 mitigated YB-1-induced sorafenib resistance. CONCLUSION: Overall, we concluded that YB-1 augments sorafenib resistance through the PI3K/Akt signaling pathway in HCC and suggest that YB-1 is a key drug resistance-related gene, which is of great significance for the application of sorafenib in advanced-stage HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Apoptose , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Proteínas de Transporte , Linhagem Celular Tumoral , Proliferação de Células , Resistencia a Medicamentos Antineoplásicos , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Fosfatidilinositol 3-Quinase/metabolismo , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Sorafenibe/farmacologia , Proteína 1 de Ligação a Y-Box
4.
Bioresour Technol ; 316: 123929, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32763805

RESUMO

This research presents the tangerine seed activated carbon (TSAC), obtained from food waste (tangerine seed) by one-step pyrolysis method and applied to remove carbamate pesticides (CMs) from complex solutions. The effects of carbonization temperature and time on adsorption performance were studied. Structural properties of TSAC were determined by Fourier Transform Infrared Spectrometer, X-ray diffraction analysis, Raman spectroscopy, scanning electron microscope and nitrogen adsorption/desorption methods and compared with that of tangerine seed. The TSAC exhibited a specific surface area of 659.62 m2/g, a total pore volume of 0.6203 cc/g and a pore diameter of 1.410 nm. The influences of initial pesticide concentration, adsorption temperature and contact time were investigated through batch experiments. Pseudo-second-order kinetic model and Langmuir isotherm model were more suitable for CMs adsorption process onto TSAC. Furthermore, the thermodynamic research indicated that this adsorption process was spontaneous and exothermic.


Assuntos
Praguicidas , Eliminação de Resíduos , Poluentes Químicos da Água/análise , Adsorção , Carbamatos , Carvão Vegetal , Concentração de Íons de Hidrogênio , Cinética , Sementes/química , Espectroscopia de Infravermelho com Transformada de Fourier , Termodinâmica , Água
5.
Scand J Gastroenterol ; 55(6): 732-736, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32567400

RESUMO

Aims: The studies on post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) in pancreas divisum (PD) patients without chronic pancreatitis (CP) are rare. In this study, we aimed to evaluate the incidence of PEP in PD patients without CP and the risk and protective factors for PEP.Methods: Consecutive patients with symptomatic PD that underwent ERCP from January 2005 to December 2017 were retrospectively analyzed. The patients were divided into PD without CP group and CP group. The basic information and medical records of patients were collected. The risk and protective factors for PEP in PD patients without CP were analyzed by univariate logistic analysis.Results: A total of 89 ERCP procedures were performed in 51 PD patients without CP, and 249 procedures in 136 patients with CP. The incidence of PEP was significantly higher in PD patients without CP than those with CP (15.7% vs. 5.6%, p = .005). Female gender were independent risk factors for PEP, while dorsal duct stent placement was a protective factor.Conclusion: CP may be a protective factor against PEP in PD patients. Female was a risk factor for PEP in PD patients and dorsal duct stent placement was a preventive factor that reduced the incidence of PEP in PD patients without CP.

6.
Mediators Inflamm ; 2020: 1945832, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32410847

RESUMO

The intestinal tract consists of various types of cells, such as epithelial cells, Paneth cells, macrophages, and lymphocytes, which constitute the intestinal immune system and play a significant role in maintaining intestinal homeostasis by producing antimicrobial materials and controlling the host-commensal balance. Various studies have found that the dysfunction of intestinal homeostasis contributes to the pathogenesis of inflammatory bowel disease (IBD). As a novel mediator, extracellular vesicles (EVs) have been recognized as effective communicators, not only between cells but also between cells and the organism. In recent years, EVs have been regarded as vital characters for dysregulated homeostasis and IBD in either the etiology or the pathology of intestinal inflammation. Here, we review recent studies on EVs associated with intestinal homeostasis and IBD and discuss their source, cargo, and origin, as well as their therapeutic effects on IBD, which mainly include artificial nanoparticles and EVs derived from microorganisms.

7.
Anal Chim Acta ; 1105: 224-230, 2020 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-32138922

RESUMO

An on-line cyclodextrin assisted sweeping-micellar electrokinetic chromatography (CD assisted sweeping-MEKC) was developed for the simultaneous separation and concentration of four neutral analytes (erianin, dendrophenol, naringenin and scoparone) in Dendrobium officinale Kimura et Migo (D. officinale). The D. officinale was directly determined by this on-line stacking method after simple extraction and dilution. The optimized background solution (BGS) was 50 mM phosphoric acid (PA) containing 100 mM SDS and 30% (v/v) methanol. The best separation and concentration performance of analytes dissolved in 90 mM CD and 100 mM PA was achieved in a short analysis time when injected at 50 mbar for 100 s. Compared with conventional sweeping-MEKC and MEKC method, significant improvement in enrichment efficiency was achieved by using this proposed method. A series of validation studies of the present method was performed under the optimal conditions. Good linearities were obtained with the correlation coefficients in the range of 0.994-0.999, the detection limits were ranged from 13 to 40 ng/mL. Sensitivity enhancement factors (SEFs) were in the range of 28.5-46.8 compared with traditional injection (injection time 3 s). Therefore, the proposed method was successfully applied for the separation and concentration of neutral analytes in real samples.


Assuntos
Compostos de Benzil/análise , Bibenzilas/análise , Cromatografia Capilar Eletrocinética Micelar , Cumarínicos/análise , Ciclodextrinas/química , Flavanonas/análise , Fenol/análise , Dendrobium/química , Micelas , Estrutura Molecular
8.
J Pharm Biomed Anal ; 182: 113118, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32004769

RESUMO

The stems of Dendrobium officinale, a well-known and expensive food material and herbal medicine in Asia, has recently suffered adulterants and counterfeits by using lower-price confusing Dendrobium species such as D. devonianum or D. transparens in the herbal market. However, robust methods that could authenticate D. officinale from its confusing species effectively are still lacking, especially for the dried samples. This study committed to discover specific peptides biomarkers for the authentication of D. officinale from the other two Dendrobium species using label-free proteomics by nanoLC LTQ Orbitrap mass spectrometry. Multivariate statistical analysis was applied to visualize the difference between the three Dendrobium species. As a result, 29 peptides among a total of 343 measurable peptides were selected to be potential biomarkers for the classification of these Dendrobium species. The validation of the representative peptide biomarkers was carried out by the synthesized peptides and 3 peptide biomarkers were found significant for the authentication of D. officinale. Further analysis showed that peptide ALGLELDLSER may also be a biomarker for the discrimination of the D. officinale originated from different geographical regions.


Assuntos
Dendrobium/química , Peptídeos/química , Extratos Vegetais/química , Proteômica/métodos , Biomarcadores/química , Dendrobium/classificação , Peptídeos/isolamento & purificação , Caules de Planta
9.
J Dig Dis ; 20(12): 656-662, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31618520

RESUMO

OBJECTIVE: We conducted a randomized trial aiming at improving patients' informed consent for undergoing endoscopic retrograde cholangiopancreatography (ERCP) in clinical care by comparing the efficacy of an additional educational video to written informed consent with that of written informed consent alone. METHODS: This was a single-center, randomized controlled trial. Consecutive patients undergoing ERCP were randomized to a video education or a control group. An educational video detailing ERCP procedure plus standard written informed consent was administered to the video education group, while the control group reviewed standard written informed consent only. The primary outcome was the patients' perception of the risk or possibility of ERCP complications. Their perception of the benefits of ERCP, alternative treatments and overall satisfaction with the process of informed consent were also compared. RESULTS: In total 205 patients were included in the study (104 in the control group and 101 in the video education group). Patients' comprehension of ERCP-related complications in the video education group was significantly increased (P < 0.001), and these patients were more likely to correctly identify the incidence of such complications. Significantly more patients in the video education group were very satisfied with informed consent process (87.1% vs 76.0%, P = 0.040) and fewer patients needed additional explanations (31.7% vs 47.1%, P = 0.024). CONCLUSIONS: A supplementary educational video could greatly improve patient's understanding of ERCP procedure, in particular, its potential risks and complications, as well as their overall satisfaction with the process of informed consent (ClinicalTrials.gov no. NCT02810379).


Assuntos
Recursos Audiovisuais , Colangiopancreatografia Retrógrada Endoscópica , Consentimento Livre e Esclarecido , Educação de Pacientes como Assunto/métodos , Colangiopancreatografia Retrógrada Endoscópica/efeitos adversos , Colangiopancreatografia Retrógrada Endoscópica/métodos , Compreensão , Feminino , Humanos , Consentimento Livre e Esclarecido/psicologia , Consentimento Livre e Esclarecido/normas , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Melhoria de Qualidade , Medição de Risco , Gestão de Riscos/legislação & jurisprudência , Gestão de Riscos/métodos , Gestão de Riscos/normas
10.
Cell Death Dis ; 10(6): 391, 2019 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-31564717

RESUMO

Psychosocial stress is a critical inducing factor of inflammatory bowel diseases (IBD), while autophagy is a novel central issue of IBD development. The present study investigated the potential role of autophagy in stress-related IBD in patients and animal model. The correlation between psychosocial stress and intestinal autophagy was determined in 23 patients with IBD. Corticotropin-releasing hormone (CRH), a well-established inducer of psychosocial stress, was administrated in dextran sulfate sodium (DSS)-induced IBD mice and lipopolysaccharide (LPS)-stimulated bone marrow-derived macrophages (BMDM). In IBD patients, the autophagy markers beclin-1, LC3-II/I ratio, Atg16L1, and Atg4B were significantly enhanced. The psychosocial stress score was positively associated with the levels of beclin-1 and the LC3II/I ratio in intestinal biopsy specimens. In IBD mouse model, CRH significantly aggravated intestinal inflammation, increased Paneth cell metaplasia, and enhanced intestinal autophagy (beclin-1, Atg16L1, PIK3R4, and Atg4B upregulation; GAA, CTSD, and PPKAA1 downregulation). Additionally, the CRH-induced gut microbial dysbiosis was evidenced by a marked increase in the number of detrimental bacteria. In LPS-stimulated BMDM, CRH substantially increased M1/M2 polarization and thus promoted inflammation. In both IBD mice and LPS-treated BMDM, blockade of autophagy by chloroquine abrogated the unbeneficial effects of CRH, whereas autophagy inducer rapamycin resulted in a pronounced protective effect against IBD lesion. Our data demonstrate that psychosocial stress may link the enhanced intestinal autophagy by modulating gut microbiota and inflammation to aggravate IBD. These data indicate autophagy as a promising therapeutic target for psychosocial stress-related IBD.


Assuntos
Autofagia , Microbioma Gastrointestinal , Doenças Inflamatórias Intestinais/patologia , Estresse Psicológico , Adulto , Animais , Autofagia/efeitos dos fármacos , Proteínas Relacionadas à Autofagia/genética , Proteínas Relacionadas à Autofagia/metabolismo , Catepsina D/genética , Catepsina D/metabolismo , Cloroquina/farmacologia , Colo/metabolismo , Colo/patologia , Hormônio Liberador da Corticotropina/farmacologia , Modelos Animais de Doenças , Feminino , Microbioma Gastrointestinal/efeitos dos fármacos , Humanos , Doenças Inflamatórias Intestinais/induzido quimicamente , Doenças Inflamatórias Intestinais/metabolismo , Ativação de Macrófagos/efeitos dos fármacos , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade
11.
Phytochem Anal ; 30(6): 710-719, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31264752

RESUMO

INTRODUCTION: The main active components in hawthorn leaves possess various biological activities such as anti-inflammatory, antioxidant, and hypolipidemic effects. Therefore, it is necessary to develop an effective and reliable extraction method to extract these active compounds from hawthorn leaves. OBJECTIVE: To establish a simple, rapid, and sensitive method for extraction and determination of polyphenolic compounds from hawthorn leaves. METHODS: In this study, a microwave-assisted reaction and extraction (MARE) combined with ultra-high-performance liquid chromatography with ultraviolet detector method was established to extract and determine the polyphenolic compounds in hawthorn leaves. The solid reagent aqueous solutions were applied as extraction solvents, preventing the use of organic solvents. The target analytes were identified by quadrupole time-of-flight tandem mass spectrometry. Several experimental parameters that can significantly affect the extraction efficiency were evaluated and optimised. RESULTS: The optimal conditions were as follows: 0.1 g of sodium carbonate was used as solid reagent, the amount of sodium borate was set at 0.01 g, extraction time was 10 min, extraction temperature was set at 50°C, pH value was adjusted to 7. The validation experiments demonstrated that the method had high sensitivity with the limits of detection in the range 26.5-37.7 ng/mL. The average recoveries ranged from 80.22% to 93.27%. CONCLUSION: In this work, the proposed MARE method was successfully applied to extract and determine polyphenolic compounds in hawthorn leaf samples. Compared with other reported methods, the present method was faster, greener, and more sensitive.


Assuntos
Crataegus/química , Micro-Ondas , Folhas de Planta/química , Concentração de Íons de Hidrogênio , Limite de Detecção , Polifenóis/análise , Reprodutibilidade dos Testes
12.
J Pharm Biomed Anal ; 175: 112738, 2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31362249

RESUMO

Turmeric (Curcuma longa L, Zingiberaceae) rhizomes exhibit versatile biological activities including the significant anti-cancer property. As an herbal medicine, the therapeutic effects of turmeric may be expressed by multi-components which have complicated integration effects on multi-targets. Therefore, having previously found three A549 cell-binding curcuminoids (curcumin, Cur; demethoxycurcumin, DMcur; bisdemethoxycurcumin, BMcur) from turmeric, studies were undertaken in this paper to determine the anti-cancer mechanism and integration effects of these curcuminoids by using chemical markers' knockout and UHPLC-LTQ Orbitrap MS-based metabolomics. Four curcuminoid-containing fractions including a mixture of 3 cell-binding curcuminoids (CE), and three individual curcuminoids with natural proportion in turmeric were prepared by chemical markers' knockout method. CE, Cur, DMcur and BMcur fractions showed significant anti-cancer activity on A549 cells. The activities of CE, Cur and BMcur fractions were comparative with the turmeric crude extract (TcE). In the metabolomics study, CE and three individual curcuminoid fractions changed the expression of 25 metabolites in A549 cells, which were involved in glycerophospholipid catabolism, sphingolipid metabolism and fatty acid metabolism, etc. Among them, glycerophospholipid catabolism was disordered greatly in CE group, while sphingolipid metabolism was suggested to be closely related to DMcur and BMcur activity. Furthermore, the metabolomics data showed that three curcuminoids existed synergistic and antagonistic actions and the use of multi-curcuminoids is more powerful than use of single curcuminoid on the metabolic alterations of A549 cells.


Assuntos
Antineoplásicos/farmacologia , Curcuma/química , Diarileptanoides/metabolismo , Diarileptanoides/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Extratos Vegetais/farmacologia , Células A549 , Antineoplásicos/metabolismo , Linhagem Celular Tumoral , Cromatografia Líquida de Alta Pressão/métodos , Curcuma/metabolismo , Curcumina/metabolismo , Curcumina/farmacologia , Humanos , Metabolômica/métodos , Fitoterapia , Extratos Vegetais/metabolismo , Rizoma/química , Rizoma/metabolismo
13.
Inflammation ; 42(5): 1666-1679, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31236857

RESUMO

Alpha7 nicotinic acetylcholine receptor (α7nAChR) has been reported to be protective in several kinds of disorders through inflammatory suppression. Here, we investigated the role of α7nAChR in inflammatory bowel disease (IBD) on α7nAChR deficient mice (α7nAChR-/-) and the wild-type mice (α7nAChR+/+). Three percent dextran sulfate sodium (DSS) was used for the creation of IBD mice model and lipopolysaccharides (LPS)/DSS as an inflammatory stressor in murine bone marrow-derived macrophages (BMDMs). The severity of IBD was determined and HE staining as well as enzyme-linked immunosorbent assay (ELISA) and real-time PCR were used to detect the level of inflammatory activation. Western blot was used to determine the levels of autophagy-related proteins. Transmission electron microscopy and mRFP-GFP-LC3 plasmid were applied to determine the levels of autophagy. We demonstrated that deficiency in α7nAChR produced a detrimental effect on IBD severity and inflammatory reaction in DSS-induced colitis models. Those effects were led to via autophagy dysfunction. α7nAChR deficiency attenuated the protective and anti-inflammatory effect of autophagy inducer in IBD mice and BMDMs challenged with LPS/DSS. The alleviative effect of activating α7nAChR was attenuated through inhibiting adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK)-mediated signaling. In conclusion, α7nAChR contributes to alleviate IBD through the induction of AMPK-mammalian target of rapamycin rabbit (mTOR)-p70 ribosomal protein S6 kinase (p70S6K)-mediated autophagy, thus providing a novel target for the treatment of IBD.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Autofagia/efeitos dos fármacos , Doenças Inflamatórias Intestinais/prevenção & controle , Proteínas Quinases S6 Ribossômicas 70-kDa/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Receptor Nicotínico de Acetilcolina alfa7/fisiologia , Animais , Camundongos , Camundongos Knockout , Coelhos , Ativação Transcricional
14.
J Dig Dis ; 20(8): 391-400, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31069993

RESUMO

OBJECTIVE: Cancer recurrence is a complicated problem for clinicians that contributes to poor prognosis. This study aimed to use advanced gastric carcinoma genes profiles to predict increased risk of cancer recurrence in order to identify patients in need of adjuvant therapy for prognosis improvement. METHODS: Differentially expressed genes were identified for advanced gastric carcinoma by analyzing the GSE2685 from the Gene Expression Omnibus database (GEO) using R package. The candidate genes were then obtained by gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, protein-protein interaction analysis and survival analysis. Logistic regression analysis was performed to determine the relationship between candidate genes and the recurrence of gastric carcinoma. RESULTS: Collagen type IV alpha 1 (COL4A1) was overexpressed in gastric carcinoma tissue by analyzing the GSE2685 gene expression profiles from the Gene Expression Omnibus database. COL4A1 was also overexpressed in gastric carcinoma tissue from the Cancer Genome Atlas dataset and further determined that higher COL4A1 expression led to poorer overall survival. A univariate analysis suggested that COL4A1 was strongly correlated with T stage and gastric carcinoma recurrence (P = 0.014 and 0.041, respectively). Moreover, a multiple logistic regression analysis indicated that COL4A1 was significantly associated with gastric carcinoma recurrence (hazard ratio 1.605, 95% confidence interval 1.063-2.677, P = 0.008). CONCLUSIONS: COL4A1 may promote gastric carcinoma recurrence and could be used as a therapeutic target for gastric carcinoma recurrence.


Assuntos
Carcinoma/genética , Colágeno Tipo IV/análise , Recidiva Local de Neoplasia/genética , Neoplasias Gástricas/genética , Adulto , Idoso , Biomarcadores Tumorais/genética , Carcinoma/mortalidade , Biologia Computacional , Bases de Dados Genéticas , Feminino , Ontologia Genética , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Prognóstico , Fatores de Risco , Neoplasias Gástricas/mortalidade , Análise de Sobrevida
15.
Inflammation ; 42(4): 1147-1159, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30937839

RESUMO

Inflammatory bowel disease (IBD) is a group of inflammatory conditions of the colon and small intestine, comprised of ulcerative colitis and Crohn's disease. Among the complicated pathogenic factors of IBD, the overaction of inflammatory and immune reaction serves as an important factor. Inflammasome is a form of innate immunity as well as inflammation. Among all kinds of inflammasomes, the NOD-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome is the most studied one, and has been revealed to be involved in the pathogenesis and progression of IBD. Here, in this review, the association between the NLRP3 inflammasome and IBD will be discussed. Furthermore, several NLRP3 inflammasome inhibitors which have been demonstrated to be effective in the alleviation of IBD will be described in this review.


Assuntos
Inflamassomos/antagonistas & inibidores , Doenças Inflamatórias Intestinais/tratamento farmacológico , Proteína 3 que Contém Domínio de Pirina da Família NLR , Animais , Colite Ulcerativa , Doença de Crohn , Humanos , Inflamassomos/química , Inflamassomos/imunologia , Inflamação/prevenção & controle , Doenças Inflamatórias Intestinais/etiologia , Doenças Inflamatórias Intestinais/patologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/imunologia
16.
J Chromatogr A ; 1602: 150-159, 2019 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-30961967

RESUMO

A rapid and effective method was successfully established for the extraction and determination of chlorogenic acid, protocatechuic acid, malic acid, caffeic acid and gallic acid in fruit (chaenomeles speciosa) via matrix solid-phase dispersion (MSPD) microextraction combined with ultra-high performance liquid chromatography with quadrupole time-of-flight tandem mass spectrometry (UHPLC-Q-TOF/MS). Several major extraction parameters were investigated and optimized, such as the type of sorbent, the amount of sorbent, the grinding time, the type and concentration of the eluting solvent. The optimal extraction conditions were obtained by using 20 mg of calix[8]arene as dispersing adsorbent, selecting 60 s as the appropriate grinding time and applying 250 mM of 1-dodecyl-3-methylimidazolium bromide as eluent solvent. Moreover, the calibration curves of the analytes were in the range of 0.01-500 µg/mL with the determination coefficients (r2) higher than 0.9995. The limits of detection and limits of quantification were in the range of 0.202-1.056 ng/mL and 0.674-3.521 ng/mL, respectively. The recoveries of the target compounds at two spiked levels were between 82.19 and 113.36%. Furthermore, this method had acceptable reproducibility (RSD ≤ 3.84%). The proposed approach combined the advantages of MSPD microextraction with UHPLC-Q-TOF/MS, and could be applicable for the analysis organic acids in fruit.


Assuntos
Calixarenos/química , Ácidos Carboxílicos/isolamento & purificação , Frutas/química , Líquidos Iônicos/química , Microextração em Fase Sólida/métodos , Adsorção , Íons/análise , Limite de Detecção , Modelos Lineares , Padrões de Referência , Reprodutibilidade dos Testes , Solventes/química , Espectrometria de Massas em Tandem , Fatores de Tempo
17.
Dig Dis Sci ; 64(8): 2088-2094, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30778871

RESUMO

BACKGROUND AND AIMS: Endoscopic biliary sphincterotomy (EST) is commonly performed during therapeutic endoscopic retrograde cholangiopancreatography (ERCP), but is an independent risk factor for post-ERCP pancreatitis, bleeding and duodenal perforation. These are partly ascribed to the electrosurgical current mode used for EST, and currently the optimal current model for EST remains controversial. In this study, we aimed to compare the rate of complications undergoing EST using the Endocut versus the blended current. METHODS: A systematic search of databases was performed for relevant published and prospective studies including randomized clinical trials (RCTs) to compare Endocut with blended current modes for EST. Data were collected from inception until 1 July 2018, using post-ERCP pancreatitis, bleeding and perforation as primary outcomes. RESULTS: Three RCTs including a total of 594 patients met the inclusion criteria. Our meta-analysis results showed the rate of post-ERCP pancreatitis, primarily mild to moderate pancreatitis, was no different between Endocut versus blended current modes [risk ratio (RR) 0.61, 95% confidence interval (CI) 0.25-1.52, P = 0.29]. However, the risk of endoscopically bleeding events, primarily mild bleeding, was lower in studies using Endocut versus blended current (RR 0.54, 95% CI 0.31-0.95, P = 0.03). Notably, none of the patients experienced perforation in these three trials. CONCLUSIONS: The rate of post-ERCP pancreatitis was not significantly different when using the Endocut versus blended current during EST. Nevertheless, compared with the blended current, Endocut reduced the incidence of endoscopically evident bleeding; however, the available data were insufficient to assess the perforation risk.


Assuntos
Colangiopancreatografia Retrógrada Endoscópica/métodos , Eletrocirurgia/métodos , Esfinterotomia Endoscópica/métodos , Colangiopancreatografia Retrógrada Endoscópica/efeitos adversos , Duodenopatias/etiologia , Eletrocirurgia/efeitos adversos , Humanos , Perfuração Intestinal/etiologia , Pancreatite/etiologia , Hemorragia Pós-Operatória/etiologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Fatores de Risco , Esfinterotomia Endoscópica/efeitos adversos , Resultado do Tratamento
19.
Eur J Gastroenterol Hepatol ; 31(2): 170-177, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30418256

RESUMO

OBJECTIVE: Adequate bowel preparation is essential for a successful colonoscopy; clinical studies suggest reinforced education can improve the preparation process. However, there have been no trials to compare WeChat directions (the most widely used social media app in China) with those of the short message service (SMS). This study was aimed to assess the effect of WeChat and SMS on the bowel preparation quality. PARTICIPANTS AND METHODS: This was a single-center, prospective, endoscopically blinded, randomized, controlled study. Patients in reinforced education groups received additional reminder messages by WeChat and SMS 2 days before colonoscopy. The primary outcome was bowel preparation quality evaluated by the Boston bowel preparation scale (BBPS) score and the rate of adequacy (BBPS score ≥6). Secondary outcomes included polyp detection rate, adenoma detection rate, and mean total adenomas detected. Patient tolerance level and subjective feelings were also evaluated. RESULTS: The total BBPS score and the percentage of adequacy were significantly higher in the reinforced education groups compared with the control (WeChat vs. control, P<0.001; SMS vs. control, P<0.001). Moreover, statistically significant differences between the two interventions were found in the total BBPS score but not in the rate of adequacy (P=0.007 and 0.561, respectively). The detection of adenomas, using multiplicity detection rate, advanced adenoma detection rate, and mean total adenomas detected, was much higher in the intervention groups (P=0.039, 0.037, and 0.019, respectively). CONCLUSION: WeChat was superior to SMS for bowel preparation, although both of them may help improving the detection of adenomas.


Assuntos
Adenoma/diagnóstico , Catárticos/uso terapêutico , Neoplasias do Colo/diagnóstico , Pólipos do Colo/diagnóstico , Colonoscopia/métodos , Educação de Pacientes como Assunto/métodos , Sistemas de Alerta , Mídias Sociais , Envio de Mensagens de Texto , Irrigação Terapêutica/métodos , Adenoma/patologia , Adulto , Idoso , Catárticos/efeitos adversos , China , Neoplasias do Colo/patologia , Pólipos do Colo/patologia , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Valor Preditivo dos Testes , Estudos Prospectivos , Irrigação Terapêutica/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
20.
J Mol Graph Model ; 86: 192-198, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30388693

RESUMO

The epoxy resin coating is a fundamental species with epoxy resins used as main components to form the final film. Unexpectedly, bulky CO2 bubbles that occasionally appeared during the curing process of epoxy resin coatings might destroy the final film properties. With an attempt to thoroughly understand the formation mechanism of CO2 bubbles and further propose countermeasures to control them, Density Function Theory (DFT) in this paper was employed to calculate the absorption process, the curing reaction and the formation mechanism of CO2 bubbles. The gas phase basicity (GB) values and pKa values of common amine curing agents were calculated. The total Gibbs free energies difference of the curing reactions between polluted curing agents and epoxy resins were calculated according to a thermodynamic cycle. Whether in gas phase or resin phase, the energetically negative ΔGsolv indicated that the curing reactions might occur spontaneously and CO2 molecules would be separated and released from amine molecules. The total Gibbs free energy calculations also revealed that the re-absorption of CO2 by the curing system was energetically unfavorable. Thus, the formation mechanism of CO2 bubbles of epoxy resin coatings could be summarize in three steps: (1) Carbon dioxide pollutes accidentally the curing agents. (2) CO2 molecules are gradually released as the curing process occurs. (3) CO2 molecules are collected to form big bubbles which can lead to seriously surface and/or internal defects. Finally, based on practical experiences three tips were proposed to control CO2 bubbles. The present results not only evidenced the nature of the unexpected bubbles of epoxy resin coatings, but also additionally paved to the way to full utilization of the formation mechanism to improve the epoxy coatings' properties.


Assuntos
Dióxido de Carbono/química , Resinas Epóxi/química , Algoritmos , Materiais Revestidos Biocompatíveis , Teoria da Densidade Funcional , Termodinâmica
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