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1.
J Clin Gastroenterol ; 58(3): 232-241, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38227844

RESUMO

BACKGROUND AND AIMS: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is a potentially valuable tool for the diagnosis of pelvic lesions. The aim of this meta­analysis was to evaluate the efficacy and feasibility of EUS-FNA in the diagnosis of pelvic lesions. METHODS: We performed a computerized search of PubMed, EMBASE, Cochrane Library, and Science Citation Index, through March 2023. The main outcome measures examined in the meta-analysis were sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy. RESULTS: We evaluated 22 trials that used surgical pathology or imaging follow-up results as the reference standard. The studies comprised 844 patients. The cumulative sensitivity, specificity, PPV, NPV, and accuracy were 94%, 100%, 100%, 89%, and 96%, respectively. In the subgroup analysis, the prospective studies revealed the cumulative sensitivity, specificity, PPV, NPV, and accuracy were 91%, 100%, 100%, 85%, and 93%, respectively. CONCLUSIONS: In conclusion, we provide evidence that EUS-FNA is a qualitative diagnostic technique with high sensitivity, specificity, PPV, and accuracy. However, its NPV is slightly low, which does not exclude the risk of a missed diagnosis, and more randomized controlled trials or prospective studies are still needed in the future. EUS-FNA is effective and feasible for pelvic space-occupying lesions. This technique has high clinical application value for pelvic lesions.


Assuntos
Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico , Neoplasias Pancreáticas , Humanos , Estudos Prospectivos , Valor Preditivo dos Testes , Sensibilidade e Especificidade , Neoplasias Pancreáticas/patologia
2.
J Inflamm Res ; 16: 6073-6086, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38107381

RESUMO

Purpose: To explore the molecular mechanisms of intestinal injury and treatment by analyzing changes in cellular heterogeneity and composition in rat ileal tissue during injury and treatment processes. Methods: We constructed a rat model of SAP and evaluated treatment with an injected of monoacylglycerol lipase (MAGL) inhibitor (JZL184) solution using three experimental groups: healthy male Sprague-Dawley (SD) rats injected with vehicle (CON), male SD SAP model rats injected with vehicle (SAP), and male SAP rats injected with JZL184. We obtained and prepared a single-cell suspension of ileal tissue of each rat for single-cell transcriptome sequencing. Results: This project classified changes in cellular heterogeneity and composition in rat ileal tissue during SAP-induced intestinal injury and MAGL treatment. We found that the number of fibroblast clusters was decreased in the SAP group relative to the CON group, and increased after JZL184 treatment. Further analysis of differences in gene expression between cell clusters in each group reveals that fibroblasts had the greatest number of differentially expressed genes. Most notably, expression of genes involved in communication between cells was found to vary during SAP-induced intestinal injury and JZL184 treatment. Among these changes, the degree of difference in expression of genes involved in communication between fibroblasts and other cells was the highest, indicating that fibroblasts in rat ileal tissue affect intestinal injury and repair through cell-to-cell communication. In addition, our results reveal that differentially expressed RNA-binding proteins in fibroblasts may affect their functions in intestinal injury and treatment by affecting the expression of genes regulating communication between cells. Conclusion: These findings emphasize the importance of understanding the interactions between fibroblasts and other cells in the context of intestinal injury, providing valuable insights for further exploring molecular mechanisms and insight for discovering new treatment targets and strategies.

4.
Exp Ther Med ; 26(6): 578, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38023358

RESUMO

Acute pancreatitis (AP) is a severe inflammatory condition characterized by the activation of pancreatic enzymes within acinar cells, leading to tissue damage and inflammation. Interleukin (IL)-22 is a potential therapeutic agent for AP owing to its anti-inflammatory properties and ability to promote tissue repair. The present study evaluated the differentially expressed proteins in arginine-induced pancreatic acinar cell injury following treatment with IL-22, and the possible mechanisms involved in IL-22-mediated alleviation of AP. AR42J cells were stimulated using L-arginine to establish an acinar cell injury model in vitro and the damaged cells were subsequently treated with IL-22. The characteristics of the model and the potential therapeutic effects of IL-22 were examined by CCK-8 assay, flow cytometry, TUNEL assay, transmission electron microscopy and ELISA. Differentially expressed proteins in cells induced by arginine and treated with IL-22 were assessed using liquid chromatography-mass spectrometry. The identified proteins were further subjected to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis to elucidate their functional roles. The present study demonstrated that arginine-stimulated cells showed significant pathological changes resembling those in AP, which were alleviated after IL-22 treatment. Proteomic analysis then demonstrated that in IL-22-treated cells, proteins related to the formation and fusion of autophagosomes with lysosomes were significantly downregulated, whereas endocytosis related proteins were enriched in the upregulated proteins. After IL-22 treatment, western blotting demonstrated reduced expression of autophagy-associated proteins. In conclusion, by inhibiting the formation and fusion of autophagosomes with lysosomes, IL-22 may have mitigated premature trypsinogen activation, subsequently minimizing acinar cell injury induced by L-arginine. This was accompanied by concurrent upregulation of endocytosis, which serves a pivotal role in sustaining regular cellular material transport and signal propagation. This research underscored the potential of IL-22 in mitigating arginine-induced AR42J injury, which could be valuable in refining treatment strategies for AP.

5.
J Agric Food Chem ; 71(38): 13950-13964, 2023 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-37698386

RESUMO

Long-term consumption of a high-sugar diet may contribute to the pathogenesis of several chronic diseases, such as obesity and type 2 diabetes. Sweet peptides derived from a wide range of food sources can enhance sweet taste without compromising the sensory properties. Therefore, the research and application of sweet peptides are promising strategies for reducing sugar consumption. This work first outlined the necessity for global sugar reduction, followed by the introduction of sweet taste receptors and their associated transduction mechanisms. Subsequently, recent research progress in sweet peptides from different protein sources was summarized. Furthermore, the main methods for the preparation and evaluation of sweet peptides were presented. In addition, the current challenges and potential applications are also discussed. Sweet peptides can stimulate sweetness perception by binding sweet taste receptors T1R2 and T1R3 in taste buds, which is an effective strategy for reducing sugar consumption. At present, sweet peptides are mainly prepared artificially by synthesis, hydrolysis, microbial fermentation, and bioengineering strategies. Furthermore, sensory evaluation, electronic tongues, and cell models have been used to assess the sweet taste intensity. The present review can provide a theoretical reference for reducing sugar consumption with the aid of sweet peptides in the food industry.


Assuntos
Diabetes Mellitus Tipo 2 , Papilas Gustativas , Humanos , Paladar/fisiologia , Edulcorantes/química , Diabetes Mellitus Tipo 2/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Papilas Gustativas/metabolismo , Carboidratos , Peptídeos/metabolismo , Açúcares/metabolismo , Açúcares da Dieta/metabolismo , Percepção Gustatória/fisiologia
6.
J Clin Gastroenterol ; 57(9): 871-878, 2023 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-37267459

RESUMO

BACKGROUND AND AIM: Endoscopic ultrasound-directed trans-gastric retrograde cholangiopancreatography (EDGE) is a new procedure for treating pancreaticobiliary diseases in patients with Roux-en-Y gastric bypass (RYGB). The aim of this meta­analysis was to determine the overall outcomes and safety of EDGE. MATERIALS AND METHODS: We performed a computerized search of the main databases, including PubMed, EMBASE, Cochrane Library, and Science Citation Index, through October 2022. The main outcome measures examined in the meta-analysis were technical and clinical success rates and overall adverse event (AE) rate, especially the lumen-apposing metal stent (LAMS) dislodgement rate. AE rates were assessed according to LAMS size (15 vs. 20 mm), number of stages (single vs. two) and access route (gastrogastric vs. jejuno-gastric). RESULTS: Fourteen trials with a total of 574 patients who had undergone 585 EDGE procedures were included in this study. The cumulative technical and clinical success and AE rates were 98%, 94%, and 14%, respectively. The commonest AE was LAMS dislodgement (rate 4%). The overall AE rate was lower in the 20-mm LAMS than in the 15-mm LAMS group (odds ratio [OR]=5.79; 95% confidence interval [CI]: 2.35 to 14.29). There were no significant differences in AE rate between number of stages (OR=1.36; 95% CI: 0.51 to 3.64) or differing access routes (OR=1.03; 95% CI 0.48 to 2.22). CONCLUSION: We here provide evidence that EDGE for endoscopic retrograde cholangiopancreatography yields good treatment outcomes in patients with RYGBs. The AE rate is significantly lower with 20-mm versus 15-mm LAMS; thus, the former is likely preferable.


Assuntos
Derivação Gástrica , Humanos , Derivação Gástrica/efeitos adversos , Derivação Gástrica/métodos , Colangiopancreatografia Retrógrada Endoscópica/efeitos adversos , Colangiopancreatografia Retrógrada Endoscópica/métodos , Estômago , Stents , Resultado do Tratamento
7.
Crit Rev Food Sci Nutr ; : 1-20, 2023 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-37366175

RESUMO

A large amount of poultry blood is annually generated, and currently underutilized or largely disposed of as waste, resulting in environmental pollution and waste of protein resources. As one of the main by-products during the poultry slaughter process, the produced poultry blood can serve as a promising food ingredient due to its excellent functional properties and abundant source of essential amino acids, bioactive peptides and functional components. This work provides a comprehensive summary of recent research progress in the composition, functional and bioactive properties, as well as the functional components of poultry blood. Furthermore, the main preparation methods of poultry blood-derived peptides and their bioactivities were reviewed. In addition, their potential applications in the food industry were discussed. Overall, poultry blood is characterized by excellent functionalities, including solubility, gelation, foaming, and emulsifying properties. The major preparation methods for poultry blood-derived peptides include enzymatic hydrolysis, ultrasound-assisted enzymatic methods, macroporous adsorbent resins, and subcritical water hydrolysis. Poultry blood-derived peptides exhibit diverse bioactivities. Their metallic off-flavors and bitterness can be improved by exopeptidase treatment, Maillard reaction, and plastein reaction. In addition, poultry blood is also abundant in functional components such as hemoglobin, superoxide dismutase, immunoglobulin, and thrombin.

8.
Int J Exp Pathol ; 104(4): 188-198, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37070207

RESUMO

Liver fibrosis is caused by chronic liver injury. There are limited treatments for it, and the pathogenesis is unclear. Therefore, there is an urgent need to explore the pathogenesis of liver fibrosis, and to try to identify new potential therapeutic targets. For this study we used the carbon tetrachloride abdominal injection induced liver fibrosis animal model in mice. Primary hepatic stellate cell isolation was performed by a density-gradient separation method, and this was followed by immunofluorescence stain analyses. Signal pathway analysis was performed by dual-luciferase reporter assay and western blotting. Our results showed that RUNX1 was upregulated in cirrhotic liver tissues compared with normal liver tissues. Besides, overexpression of RUNX1 caused more severe liver fibrosis lesions than control group under CCl4 -induced conditions. Moreover, α-SMA expression in the RUNX1 overexpression group was significantly higher than in the control group. Interestingly, we found that RUNX1 could promote the activation of TGF-ß/Smads in a dual-luciferase reporter assay. Thus we demonstrated that RUNX1 could be considered as a new regulator of hepatic fibrosis by activating TGF-ß/Smads signalling. Based on this, we concluded that RUNX1 may be developed as a new therapeutic target in the treatment of liver fibrosis in the future. In addition, this study also provides a new insight about the aetiology of liver fibrosis.


Assuntos
Subunidade alfa 2 de Fator de Ligação ao Core , Cirrose Hepática , Animais , Camundongos , Subunidade alfa 2 de Fator de Ligação ao Core/genética , Subunidade alfa 2 de Fator de Ligação ao Core/metabolismo , Fígado/metabolismo , Cirrose Hepática/metabolismo , Transdução de Sinais , Fator de Crescimento Transformador beta/metabolismo
9.
Front Pharmacol ; 13: 965348, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36003500

RESUMO

[This corrects the article DOI: 10.3389/fphar.2022.869482.].

10.
Histol Histopathol ; 36(7): 765-773, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34132383

RESUMO

BACKGROUND: The histopathological discrepancy between endoscopic forceps biopsy (EFB) and post-resection specimens is considered a practical clinical problem. This retrospective study aimed to determine the current diagnostic concordance between the EFB and surgical specimens of colorectal cancer (CRC) and then investigated the useful factors in EFB diagnosis. METHODS: We used the representative pathological data of 2188 CRCs. The comparison of histopathological discrepancy between EFB and the related surgical specimens was performed. Furthermore, 418 biopsy specimen slides in our hospital were reviewed to determine the classification of intratumor desmoplastic reaction (DR). RESULTS: Among the 2188 patients, the positive sensitivity of EFB for adenocarcinoma was 82.7%. The discrepancy rate between the EFB and surgical specimens was 10.8-40.0% corresponding to different T stages. On the basis of DR classification, 32, 131, and 255 tumors were categorized as little, moderate and extensive, respectively. The correlation between DR classification and tumor invasion based on T stage was significant (Spearman's rho= 0.112; p<0.05). The extensive DR provided better estimates for advanced tumors than the little and moderate DR (χ²= 3.977, p=0.046). Besides DR, factors including deeper cutting the slides and histological types were significantly associated with "adenocarcinoma" diagnosis in EFB of CRCs (p<0.05). CONCLUSION: To the best of our knowledge, this is the first time that a DR classification specifically for EFB specimens was proposed. It might contribute to improve the accuracy of biopsy-based diagnosis of CRC.


Assuntos
Adenocarcinoma/classificação , Biópsia , Colonoscopia , Neoplasias Colorretais/classificação , Adenocarcinoma/diagnóstico , Adenocarcinoma/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Instrumentos Cirúrgicos , Adulto Jovem
11.
Exp Mol Pathol ; 121: 104644, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33945806

RESUMO

(AP) is a kind of inflammatory misorder existing in pancreas. Non-coding RNAs (ncRNAs) have been reported to play important roles in development of AP. The current study was designed to explore the role of circular RNA zinc finger protein 644 (circRNA circ_ZFP644) in caerulein-induced AR42J cells. AP model in vitro was established by exposure of rat pancreatic acinar AR42J cells to caerulein. Amylase activity was measured using a kit. Enzyme-linked immunosorbent assay (ELISA) was performed to examine the levels of several inflammatory factors. The expression of circ_ZFP644, microRNA (miR)-106b and protein inhibitor of activated STAT 3 (Pias3) was detected by quantitative real-time PCR (qRT-PCR) or western blot assay. And flow cytometry was employed to monitor cell apoptosis. Western blot assay was also conducted to analyze the expression of apoptosis-related proteins. The association among circ_ZFP644, miR-106b and Pias3 was validated by dual-luciferase reporter assay. Caerulein treatment activated amylase activity and promoted the secretion of inflammatory cytokines in AR42J cells. Circ_ZFP644 and Pias3 were downregulated, but miR-106b was upregulated in caerulein-induced AR42J cells. Enforced expression of circ_ZFP644 or miR-106b inhibition could reduce amylase activity and inflammatory cytokine secretion, while promote apoptosis in caerulein-induced AR42J cells, which was almost reversed by Pias3 knockdown. Circ_ZFP644 targeted miR-106b to upregulate Pias3 expression. Circ_ZFP644 might exert its anti-inflammation and pro-apoptosis roles in caerulein-induced AR42J cells by regulating miR-106b/Pias3 axis.


Assuntos
Células Acinares/efeitos dos fármacos , Ceruletídeo/toxicidade , Inflamação/prevenção & controle , MicroRNAs/genética , Chaperonas Moleculares/metabolismo , Pâncreas/efeitos dos fármacos , Proteínas Inibidoras de STAT Ativados/metabolismo , RNA Circular/administração & dosagem , Células Acinares/metabolismo , Células Acinares/patologia , Animais , Regulação da Expressão Gênica , Inflamação/induzido quimicamente , Inflamação/metabolismo , Inflamação/patologia , Chaperonas Moleculares/genética , Pâncreas/metabolismo , Pâncreas/patologia , Proteínas Inibidoras de STAT Ativados/genética , RNA Circular/genética , Ratos
12.
ACS Chem Neurosci ; 12(5): 845-856, 2021 03 03.
Artigo em Inglês | MEDLINE | ID: mdl-33586968

RESUMO

Interactions between the hypothalamic-pituitary-adrenal axis and the central 5-HT system in the depressive state remain largely unknown. The present study investigated corticosterone (CORT) regulations of extracellular 5-HT in the hippocampal CA3 in a mouse model of depression. Basal dialysate 5-HT, true extracellular 5-HT, 5-HT reuptake efficiency, and time courses of dialysate 5-HT following CORT injections at 10, 20, and 40 mg/kg were determined at baseline, depressive-like state and after subsequent fluoxetine (FLX) treatment using in vivo microdialysis in male C57BL/6 mice. Behavioral tests were used to determine behavioral phenotypes and therapeutic responses to FLX. Depressed mice showed decreased extracellular 5-HT, increased 5-HT reuptake efficiency, and absence of the increase in dialysate 5-HT response to CORT injections, which were all reversed in FLX-responsive mice. Surprisingly, the FLX nonresponsive mice continued to worsen behaviorally and exhibited lower extracellular 5-HT and higher 5-HT reuptake efficiency. Our study indicates that abolished-CORT induced 5-HT response, decreased extracellular 5-HT, and increased 5-HT reuptake efficiency might be the signature features associated with depressive-like state. Increased 5-HT reuptake efficiency was one of the underlying mechanisms, with target effectors remaining to be explored. The findings in the FLX nonresponsive mice suggest distinct neuromechanisms, which might be genetically predetermined.


Assuntos
Corticosterona , Serotonina , Animais , Fluoxetina/farmacologia , Hipocampo , Sistema Hipotálamo-Hipofisário , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Sistema Hipófise-Suprarrenal
13.
J Gastrointest Oncol ; 12(6): 2631-2642, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35070393

RESUMO

BACKGROUND: Cholangiocarcinoma (CCA), which consists of intrahepatic CCA (iCCA), perihilar CCA (pCCA), and distal CCA (dCCA), is an aggressive malignancy worldwide. PCCA and dCCA are often classified as extrahepatic CCA (exCCA). However, the differences in mutational characteristics between pCCA and dCCA remain unclear. METHODS: Deep sequencing targeting of 450 cancer genes was performed for genomic alteration detection. The tumor mutational burden (TMB) was measured by an algorithm developed in-house. Correlation analysis was conducted using Fisher's exact test. RESULTS: FGFR2 and ERBB2 mutations mainly occurred in iCCA and exCCA, respectively. In exCCA, the frequencies of PIK3CA, FAT4, KDM6A, MDM2, and TCF7L2 mutations were significantly higher in pCCA compared to dCCA, while the frequencies of TP53 and KRAS mutations were markedly lower in pCCA than those in dCCA. The prognosis-related mutations were different among the CCA subtypes. NF1 mutation was associated with short disease-free survival (DFS) and overall survival (OS), and ERBB2 mutation was associated with short DFS in dCCA patients. Meanwhile, MAP2K4 mutation was associated with long DFS and OS, and TERT mutation was associated with short DFS in pCCA. A series of mutations in genes, including ARID1A, ARID2, SMAD4, TERT, TP53, and KRAS, were found to be associated with the TMB. CONCLUSIONS: In this study, we investigated the comprehensive genomic characterizations of CCA patients, identified the significant alterations in each subtype, and identified potential biomarkers for prognosis prediction. These results provide molecular evidence for the heterogeneity of CCA subtypes and evidence for further precision targeted therapy of CCA patients.

14.
J Clin Gastroenterol ; 55(2): 103-109, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-33136779

RESUMO

BACKGROUND AND STUDY AIM: There is limited evidence on the diagnostic performance of the stylet slow-pull (SP) method for endoscopic ultrasound-guided fine-needle aspiration/biopsy. The aim of this study was to compare the SP method with standard suction (SS) for endoscopic ultrasound-guided fine-needle aspiration/biopsy of solid pancreatic masses. METHODS: A computerized bibliographic search of the main databases, including PubMed, EMBASE, Cochrane Library, and Science Citation Index, was performed through February 2020. The main outcome measurements were diagnostic accuracy, cellularity, low blood contamination, adequate core tissue acquisition, and technical success rate. RESULTS: Eleven studies (including 6 randomized trials) were included, with a total of 504 patients who underwent SP and 551 who underwent SS. Diagnostic accuracy was significantly superior in the SP group, compared with the SS group [odds ratio (OR)=1.60; 95% confidence interval (CI), 1.14-2.26]. The SP group had higher pooled rates of low blood contamination (OR=1.93; 95% CI, 1.29-2.87) and adequate core tissue acquisition (OR=1.91; 95% CI, 1.11-3.26) than the SS group. There was no significant difference between groups in the adequacy of cellularity (OR=0.99; 95% CI, 0.63-1.57; P=0.98) or technical success rate (OR=0.38; 95% CI, 0.13-1.15; P=0.09). CONCLUSIONS: The authors provide evidence that SP is superior to SS in diagnostic accuracy, low blood contamination, and adequate core tissue acquisition, without reducing adequacy of cellularity or technical success rate.


Assuntos
Neoplasias Pancreáticas , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico , Humanos , Neoplasias Pancreáticas/diagnóstico por imagem , Sensibilidade e Especificidade , Sucção
15.
Medicine (Baltimore) ; 99(24): e20721, 2020 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-32541523

RESUMO

The aim of this study was to compare the efficacy and safety of cap-assisted endoscopic injection sclerotherapy (EIS) versus direct EIS in the management of esophageal variceal bleeding in patients with cirrhosis.This retrospective study included patients with cirrhosis and esophageal variceal bleeding who underwent EIS with or without the use of a transparent cap at Shandong Provincial Hospital between December 2014 and April 2017. Patients were divided into two groups: Group A (EIS with transparent cap, n = 50) and Group B (direct EIS, n = 45). Data collected included patients' demographics, procedure details, and rates of variceal eradication, variceal rebleeding, variceal recurrence, and survival during the follow-up period. All data were expressed as mean ±â€ŠSD. Quantitative variables were compared with Student t test; qualitative variables were compared with the Fisher exact test or chi-square test. P values less than .05 were considered significant.The mean follow-up duration was similar in both groups (16.3 ±â€Š10.2 mo in Group A and 15.5 ±â€Š9.5 mo in Group B). The volume of sclerosant (64.86 ±â€Š10.62 vs 104.73 ±â€Š21.25 ml, P = .044), mean number of sessions (2.37 ±â€Š1.15 vs 5.70 ±â€Š1.57, P = .042), time required to perform endoscopic treatment (6.57 ±â€Š1.50 vs 11.22 ±â€Š2.29 minutes, P = .049), and time to initial esophageal varices eradication (5.43 ±â€Š1.38 vs 8.93 ±â€Š1.5 wk, P = .041) were significantly smaller in the cap-assisted EIS group than in the direct EIS group. The probability of variceal recurrence and rebleeding was significantly higher in the direct EIS group than in the cap-assisted EIS group (14% versus 35.6% and 20% versus 40%). Only 22 patients (44%) developed complications in the cap-assisted group versus 30 patients (66.7%) in the EIS group (P = .039). The probability of survival was similar in both groups (86% versus 75.6%, P = .133).Modified EIS with the use of a transparent cap resulted in lower rates of esophageal variceal recurrence, rebleeding, and complications, compared with direct EIS.


Assuntos
Endoscopia , Varizes Esofágicas e Gástricas/terapia , Escleroterapia/métodos , Adulto , Desenho de Equipamento , Varizes Esofágicas e Gástricas/complicações , Feminino , Humanos , Injeções/instrumentação , Cirrose Hepática/complicações , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Escleroterapia/instrumentação , Resultado do Tratamento
16.
Behav Brain Res ; 389: 112618, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32360167

RESUMO

Dorsal raphe (DR) and median raphe (MR) 5-HT neurons are two distinct sub-systems known to be regulated by 5-HT1A and 5-HT1B auto-receptors. Whether the auto-receptors in each sub-system are functionally altered in depressive-like state remains unknown. The present study is aimed to study a specific circuit (DR-ventral hippocampus and MR-dorsal hippocampus) within each sub-system to investigate changes in receptor sensitivity in the pathogenesis of depression. A mouse model of depression was developed through the social defeat paradigm, and was then treated with fluoxetine (FLX). 5-HT1A auto-receptor in the neuronal cell body (DR or MR) and 5-HT1B auto-receptor in the axonal terminal (ventral or dorsal hippocampus) were directly targeted by local perfusion of antagonists (5-HT1A: WAY100635; 5-HT1B: GR127935) through reverse microdialysis. Time courses of dialysate 5-HT measured at the axonal terminal were subsequently determined for each circuit. At baseline, 5-HT1A and 5-HT1B antagonists dose-dependently increased dialysate 5-HT, with sub-circuit specificity. In the depressive-like state, greater increases in dialysate 5-HT were observed only in the DR-ventral hippocampus circuit following local delivery of both antagonists, which were then fully restored following the FLX treatment. In contrast, no changes were observed in the MR-dorsal hippocampus circuit. Our results demonstrate differential changes in sensitivities of 5-HT1A and 5-HT1B auto-receptors in the DR-ventral hippocampus and MR-dorsal hippocampus circuits. 5-HT1A and 5-HT1B auto-receptors in the DR-ventral hippocampus circuit are sensitized in the depressive-like state. Taken together, these results suggest that the DR sub-system maybe the neural substrate mediating depressive phenotypes.


Assuntos
Autorreceptores/metabolismo , Depressão/metabolismo , Núcleo Dorsal da Rafe/metabolismo , Hipocampo/metabolismo , Neurônios/metabolismo , Receptor 5-HT1A de Serotonina/metabolismo , Receptor 5-HT1B de Serotonina/metabolismo , Animais , Masculino , Camundongos Endogâmicos C57BL , Microdiálise , Vias Neurais/metabolismo , Comportamento Social
17.
Biochem Biophys Res Commun ; 525(4): 962-967, 2020 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-32173532

RESUMO

The endocannabinoid 2-arachidonoylglycerol (2-AG) is an anti-nociceptive lipid, which is inactivated through cellular uptake and subsequent catabolism by monoacylglycerol lipase (MAGL). The present study aimed to explore the effects of inhibition of MAGL on intestinal permeability. We first tested it in differentiated CaCO2 cells after 21 days' culture. The rat model of water avoidance stress (WAS) was established, and rats were divided into four groups according to intervention. Rats received intraperitoneal injection (i.p.) of an MAGL inhibitor (JZL184) alone, JZL184 and a the cannabinoid receptor 1 (CB1) receptor antagonist (SR141716A), JZL184 and a cannabinoid receptor 2 (CB2) receptor antagonist (AM630) or vehicle alone (control). We analyzed the fluorescein isothiocyanate-dextran (FD4) permeability and 2-AG level. Expression of MAGL and tight-junction-associated proteins were detected by western blot. Compared with the control group, MAGL expression was higher and 2-AG levels lower among WAS rats. Intestinal permeability was increased following administration of JZL184 which occurred due to up-regulation of tight-junction-associated proteins Claudin-1, Claudin-2, Claudin-5 and Occludin. The effects of MAGL inhibition were mediated by CB1, indicating that MAGL may represent a novel target for the treatment of reduced intestinal permeability in the context of chronic stress.


Assuntos
Ácidos Araquidônicos/metabolismo , Endocanabinoides/metabolismo , Glicerídeos/metabolismo , Mucosa Intestinal/metabolismo , Monoacilglicerol Lipases/antagonistas & inibidores , Receptor CB1 de Canabinoide/metabolismo , Receptor CB2 de Canabinoide/antagonistas & inibidores , Estresse Fisiológico/efeitos dos fármacos , Animais , Benzodioxóis/administração & dosagem , Células CACO-2 , Claudina-1/metabolismo , Claudina-2/metabolismo , Claudina-5/metabolismo , Modelos Animais de Doenças , Humanos , Indóis/administração & dosagem , Mucosa Intestinal/efeitos dos fármacos , Intestinos/efeitos dos fármacos , Intestinos/fisiologia , Masculino , Monoacilglicerol Lipases/metabolismo , Ocludina/metabolismo , Permeabilidade/efeitos dos fármacos , Piperidinas/administração & dosagem , Ratos , Ratos Wistar , Estresse Fisiológico/genética , Estresse Fisiológico/fisiologia
18.
Onco Targets Ther ; 12: 8905-8914, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31802902

RESUMO

OBJECTIVE: MicroRNA (miRNA) is an endogenous, non-coding small RNA that plays a key role in regulating organism biology and pathology. The aim of this study was to investigate the expression characteristics of microRNA-186-5p in esophageal cancer (ECa) and its correlation with clinical progression and prognosis, and to further explore its underlying mechanisms. METHODS: Real-time quantitative PCR (qRT-PCR) was used to detect microRNA-186-5p level in 45 pairs of ECa tissue samples and adjacent ones, and to analyze the expression of microRNA-186-5p and clinical progression of ECa and prognosis. The relationship between microRNA-186-5p level in ECa cell lines was further verified by qRT-PCR. Finally, the potential mechanism was explored using luciferase reporter gene assay and cell recovery experiment. RESULTS: QRT-PCR results revealed that the expression of microRNA-186-5p in ECa tissues was remarkably lower than that in adjacent tissues, and the difference was statistically significant. Compared with patients with high expression of microRNA-186-5p, patients with low expression of microRNA-186-5p had higher incidence of pathological stage and lower overall survival rate. Besides, compared with the miR-NC group, the microRNA-186-5p mimics group had a significant decrease in proliferation and metastasis ability of ECa cells. Subsequent qRT-PCR validation in ECa cell lines and tissues indicated a significant increase in HOXA9 expression and a negative correlation with microRNA-186-5p. CONCLUSION: The expression of microRNA-186-5p was remarkably decreased in ECa, which was remarkably correlated with pathological stage, distant metastasis and poor prognosis of ECa. The results suggested that microRNA-186-5p may inhibit cell proliferation of ECa by regulating HOXA9.

20.
Brain Res ; 1714: 166-173, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-30794767

RESUMO

Corticosterone (CORT) has long been shown to modulate 5-HT system, and to alter hippocampal functions in various physiological and pathological conditions. However, CORT-elicited changes in the hippocampal 5-HT transmission and the immobility phenotype had not been fully addressed. The current study sought to explore effects of acute CORT subcutaneously injected at 10, 20, 40 mg/kg on the extracellular 5-HT in the hippocampus and the immobility time in male CD-1 mice. Following an injection of CORT or vehicle, time course of the extracellular 5-HT in the hippocampal CA3 was determined using in vivo microdialysis. The immobility time was measured at 0 min, 60 min, 120 min, 180 min in the forced swimming test (FST) and the tail suspension test (TST), respectively. Results showed that the vehicle, used to dissolve CORT, did not affect the dialysate 5-HT, nor the immobility time, by comparing the pre- and post-injection. CORT was found to dose-dependently increase the dialysate 5-HT and decrease the immobility time when compared to their vehicle-treated controls. The peak increase in the dialysate 5-HT and the decrease in the immobility time were both obtained at the 120 min following the CORT injection. Furthermore, a negative correlation was detected between the immobility time and the peak increase in the dialysate 5-HT. Our results indicated that acute CORT injection elicits antidepressant-like actions on the hippocampal 5-HT and the immobility time. The study suggested that hippocampal 5-HT responses may be one of the neurochemical bases for the immobility phenotype following CORT injection.


Assuntos
Corticosterona/farmacologia , Hipocampo/efeitos dos fármacos , Serotonina/metabolismo , Animais , Antidepressivos/metabolismo , Comportamento Animal/efeitos dos fármacos , Encéfalo/metabolismo , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Corticosterona/metabolismo , Depressão/tratamento farmacológico , Depressão/genética , Elevação dos Membros Posteriores , Hipocampo/metabolismo , Masculino , Camundongos , Natação , Lobo Temporal/metabolismo
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