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BACKGROUND: Helicobacter pylori (H. pylori) is the predominant etiological agent of gastritis and disrupts the integrity of the gastric mucosal barrier through various pathogenic mechanisms. After H. pylori invades the gastric mucosa, it interacts with immune cells in the lamina propria. Macrophages are central players in the inflammatory response, and H. pylori stimulates them to secrete a variety of inflammatory factors, leading to the chronic damage of the gastric mucosa. Therefore, the study aims to explore the mechanism of gastric mucosal injury caused by inflammatory factors secreted by macrophages, which may provide a new mechanism for the development of H. pylori-related gastritis. METHODS: The expression and secretion of CCL3 from H. pylori infected macrophages were detected by RT-qPCR, Western blot and ELISA. The effect of H. pylori-infected macrophage culture medium and CCL3 on gastric epithelial cells tight junctions were analyzed by Western blot, immunofluorescence and transepithelial electrical resistance. EdU and apoptotic flow cytometry assays were used to detect cell proliferation and apoptosis levels. Dual-luciferase reporter assays and chromatin immunoprecipitation assays were used to study CCL3 transcription factors. Finally, gastric mucosal tissue inflammation and CCL3 expression were analyzed by hematoxylin and eosin staining and immunohistochemistry. RESULTS: After H. pylori infection, CCL3 expressed and secreted from macrophages were increased. H. pylori-infected macrophage culture medium and CCL3 disrupted gastric epithelial cells tight junctions, while CCL3 neutralizing antibody and receptor inhibitor of CCL3 improved the disruption of tight junctions between cells. In addition, H. pylori-infected macrophage culture medium and CCL3 recombinant proteins stimulated P38 phosphorylation, and P38 phosphorylation inhibitor improved the disruption of tight junctions between cells. Besides, it was identified that STAT1 was a transcription factor of CCL3 and H. pylori stimulated macrophage to secret CCL3 through the JAK1-STAT1 pathway. Finally, after mice were injected with murine CCL3 recombinant protein, the gastric mucosal injury and inflammation were aggravated, and the phosphorylation level of P38 was increased. CONCLUSIONS: In summary, our findings demonstrate that H. pylori infection stimulates macrophages to secrete CCL3 via the JAK1-STAT1 pathway. Subsequently, CCL3 damages gastric epithelial tight junctions through the phosphorylation of P38. This may be a novel mechanism of gastric mucosal injury in H. pylori-associated gastritis.
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Quimiocina CCL3 , Mucosa Gástrica , Infecções por Helicobacter , Helicobacter pylori , Macrófagos , Helicobacter pylori/fisiologia , Quimiocina CCL3/metabolismo , Quimiocina CCL3/genética , Animais , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patologia , Mucosa Gástrica/microbiologia , Macrófagos/metabolismo , Macrófagos/microbiologia , Camundongos , Infecções por Helicobacter/metabolismo , Infecções por Helicobacter/patologia , Homeostase , Camundongos Endogâmicos C57BL , Humanos , Apoptose , Proliferação de Células , Masculino , Células RAW 264.7RESUMO
Helicobacter pylori (H. pylori) is a gram-negative bacteria with a worldwide infection rate of 50%, known to induce gastritis, ulcers and gastric cancer. The interplay between H. pylori and immune cells within the gastric mucosa is pivotal in the pathogenesis of H. pylori-related disease. Following H. pylori infection, there is an observed increase in gastric mucosal macrophages, which are associated with the progression of gastritis. H. pylori elicits macrophage polarization, releases cytokines, reactive oxygen species (ROS) and nitric oxide (NO) to promote inflammatory response and eliminate H. pylori. Meanwhile, H. pylori has developed mechanisms to evade the host immune response in order to maintain the persistent infection, including interference with macrophage phagocytosis and antigen presentation, as well as induction of macrophage apoptosis. Consequently, the interaction between H. pylori and macrophages can significantly impact the progression, pathogenesis, and resolution of H. pylori infection. Moreover, macrophages are emerging as potential therapeutic targets for H. pylori-associated gastritis. Therefore, elucidating the involvement of macrophages in H. pylori infection may provide novel insights into the pathogenesis, progression, and management of H. pylori-related disease.
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Gastrite , Helicobacter pylori , Humanos , Macrófagos , Fagocitose , ApoptoseRESUMO
BACKGROUND: Patients are recommended not to drive for at least the first 24 h after endoscopy with propofol sedation. However, the evidence underlying these recommendations is scarce. We hypothesized that after endoscopic procedures performed under propofol sedation, the subject's driving ability was restored in less than 24 h. METHODS: We prospectively enrolled thirty patients between 20 and 70 years possessing a legitimate driver's license scheduled for endoscopy at our hospital. The sample chosen was a convenience sample. Gastroscopy or colonoscopy was performed with propofol sedation. Before and after endoscopy, the investigator drove the subjects to the laboratory to assess their driving skills using a driving simulation system, which employs 3 driving scenarios designed by professional transportation researchers. The blood propofol concentration was estimated before endoscopy, and 2 and 4 h after endoscopy. The primary outcome was the time required for subjects to recover their driving ability after propofol sedation. The secondary outcome was the blood propofol concentration before and after endoscopic procedures under propofol anesthesia. RESULTS: Thirty volunteers participated in the study and 18 of them completed all the interventions. In the low-risk S-curve scene, the mean acceleration, lane deviation, and number of deviations from the path at baseline (0.016 cm/s2, 42.50 cm, and 0.83, respectively) were significantly less than that at post-2 h (0.029 cm/s2, P = 0.001; 53.80 cm, P = 0.014; 2.06, P = 0.022). In the moderate-(overtaking) and high-risk (emergency collision avoidance) scenes, the tested parameters at baseline and post-2 h were statistically comparable. In the low-, moderate-, and high-risk scenes the tested parameters at baseline and post-4 h were statistically comparable. The total range of propofol was 120-280 mg.The mean blood concentration of propofol at post-2 h was 0.81 ± 0.40 µg/mL, and at post-4 h was below the limit of detection. CONCLUSION: After endoscopy performed under propofol sedation, subjects' driving abilities were completely restored at 4 h when tested on a simulator.
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Anestesia , Endoscopia Gastrointestinal , Hipnóticos e Sedativos , Propofol , Humanos , Anestesia/efeitos adversos , Hipnóticos e Sedativos/administração & dosagem , Projetos Piloto , Propofol/administração & dosagem , Estudos Prospectivos , Período de Recuperação da AnestesiaRESUMO
BACKGROUND: Earlier studies suggest that probiotics have protective effects in the prevention of respiratory tract infections (RTIs). Whether such benefits apply to RTIs of viral origin and mechanisms supporting the effect remain unclear. AIM: To determine the role of gut microbiota modulation on clinical and laboratory outcomes of viral RTIs. METHODS: We conducted a systematic review of articles published in Embase and MEDLINE through 20 April 2020 to identify studies reporting the effect of gut microbiota modulation on viral RTIs in clinical studies and animal models. The incidence of viral RTIs, clinical manifestations, viral load and immunological outcomes was evaluated. RESULTS: We included 58 studies (9 randomized controlled trials; 49 animal studies). Six of eight clinical trials consisting of 726 patients showed that probiotics administration was associated with a reduced risk of viral RTIs. Most commonly used probiotics were Lactobacillus followed by Bifidobacterium and Lactococcus. In animal models, treatment with probiotics before viral challenge had beneficial effects against influenza virus infection by improving infection-induced survival (20/22 studies), mitigating symptoms (21/21 studies) and decreasing viral load (23/25 studies). Probiotics and commensal gut microbiota exerted their beneficial effects through strengthening host immunity. CONCLUSION: Modulation of gut microbiota represents a promising approach against viral RTIs via host innate and adaptive immunity regulation. Further research should focus on next generation probiotics specific to viral types in prevention and treatment of emerging viral RTIs.
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Microbioma Gastrointestinal , Probióticos , Infecções Respiratórias , Animais , Bifidobacterium , Humanos , Lactobacillus , Infecções Respiratórias/prevenção & controleRESUMO
BACKGROUND AND AIM: To investigate the efficacy and safety of premedication with simethicone/Pronase during esophagogastroduodenoscopy (EGD) with sedation. METHODS: Six hundred and ten patients were randomly allocated to two groups based on type of premedication given. Premedication used in the control group was 10 mL lidocaine hydrochloride mucilage (LHM, N = 314) and premedication used in the intervention group was 80 mL simethicone/Pronase solution plus 10 mL lidocaine hydrochloride mucilage (SP/LHM, N = 296). EGD was done under sedation. Visibility scores, number of mucosal areas that needed cleansing, water consumption for cleansing, time taken for examination, diminutive lesions, pathological diagnosis, patients' gag reflex and oxygenation (pulse oximetry) were recorded. RESULTS: SP/LHM has significantly lower total visibility score than LHM (7.978 ± 1.526 vs 6.348 ± 1.097, P < 0.01). During the procedure, number of intragastric areas that needed cleansing and amount of water consumed were significantly less in the SP/LHM than in the LHM group (P < 0.01). In SP/LHM (P = 0.01), endoscopy procedure duration was significantly longer. Although there was no significant difference in rate of detection of diminutive lesions between LHM and SP/LHM, the endoscopist carried out more biopsies in SP/LHM. This led to a higher rate of diagnosis of atrophic gastritis (P = 0.014) and intestinal metaplasia (P = 0.024). There was no significant difference in gag reflex (P = 0.604) and oxygenation during the endoscopy procedure for either group of patients. CONCLUSION: Routine use of premedication with simethicone/Pronase should be recommended during EGD with sedation.
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Sedação Consciente/métodos , Detecção Precoce de Câncer/métodos , Endoscopia Gastrointestinal/métodos , Pré-Medicação/métodos , Pronase/farmacologia , Simeticone/farmacologia , Neoplasias Gástricas/diagnóstico , Adolescente , Adulto , Idoso , Antiespumantes/farmacologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Método Simples-Cego , Adulto JovemRESUMO
The aim of this position statement is to reinforce the key points of hygiene in digestive endoscopy. The present article details the minimum hygiene requirements for reprocessing of endoscopes and endoscopic devices, regardless of the reprocessing method (automated washer-disinfector or manual cleaning) and the endoscopy setting (endoscopy suite, operating room, elective or emergency procedures). These minimum requirements are mandatory for patient safety. Both advanced diagnostic and therapeutic endoscopies should be carried out in an environment that is safe for patients and staff. Particular attention is given to contaminants. Procedural errors in decontamination, defective equipment, and failure to follow disinfection guidelines are major factors contributing to transmission of infection during endoscopy. Other important risk factors include inadequate cleaning, use of older endoscopes with surface and working channel irregularities, and contamination of water bottles or irrigating solutions. Infections by multidrug-resistant organisms have become an increasing problem in health-care systems worldwide. Since 2010, outbreaks of multidrug-resistant bacteria associated with endoscopic retrograde cholangiopancreatography have been reported from the USA, France, Germany, and The Netherlands. In many endoscopy units in Asia and the Middle East, reprocessing procedures have lagged behind those of Western countries for cultural reasons or lack of financial resources. This inconsistency in standards is now being addressed, and the World Endoscopy Organization has prepared this position statement to highlight key points for quality assurance in any endoscopy unit in any country.
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Consenso , Endoscópios , Endoscopia do Sistema Digestório/normas , Gastroenterologia , Higiene/normas , Sociedades Médicas , Ásia , Humanos , Oriente MédioRESUMO
Background: Colorectal cancer is a predominant contributor to global cancer-related morbidity and mortality. The oncogene PTOV1 has been linked to various human malignancies, yet its specific role in CRC pathogenesis requires further elucidation. Methods: Our study used a comprehensive array of authoritative bioinformatics tools, such as TIMER, UCSC Xena, GEO, Human Protein Atlas, UALCAN, CIBERSORTx and others which used to investigate the complex effects of PTOV1 on gene expression profiles, diagnostic and prognostic biomarkers, tumor immunology, signaling pathways, epigenetic alterations, and genetic mutations. Gene expression validation was conducted using Western blot and qRT-PCR. The in vitro proliferative and migratory potentials of CRC cells were evaluated using CCK-8 assays, colony formation, and transwell migration assays, respectively. MSP was applied to assess the methylation status of the PTOV1 promoter region. Results: Our results reveal a significant association between increased PTOV1 expression, driven by promoter hypomethylation, and poor patient prognosis in CRC. Elevated PTOV1 levels were positively correlated with the enrichment of diverse immune cell subsets and immune-related molecules within the tumor microenvironment. In vitro assays demonstrated that PTOV1 knockdown markedly reduced CRC cell proliferation, colony formation, and migration, while ectopic PTOV1 expression had the opposite effect. Importantly, PTOV1 was shown to regulate the PI3K-AKT signaling pathway, significantly influencing the phosphorylation of AKT1 and the expression of cell cycle regulators P21 and P27. The pharmacological inhibition of AKT1 phosphorylation using MK2206 effectively counteracted the proliferative effects induced by PTOV1 overexpression. Conclusion: The ability of PTOV1 to enhance CRC cell proliferation via modulation of the AKT1 signaling pathway establishes it as a potential therapeutic target and a promising biomarker for prognostic stratification in CRC.
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BACKGROUND: Heparin-binding growth factor signaling is involved in the pathogenesis and development of human cancers. It can be regulated by sulfation of cell-surface heparan sulfate proteoglycans (HSPG). SULF1 is a heparin-degrading endosulfatase which can modulate the sulfation of HSPGs. AIM: The purpose of this study was to elucidate the role of SULF1 in modulating proliferation and invasion of esophageal squamous cell carcinoma (ESCC) by decreasing heparin-binding growth factor signaling. METHODS: We restored SULF1 expression in the ESCC cell line KYSE150, and examined the effects of SULF1 expression on the proliferation and invasion of KYSE150 cells. In addition, we investigated the expression of SULF1 in human ESCC tissues and analyzed the correlation of SULF1 expression with clinicopathologic characteristics of ESCC. RESULTS: Our study shows that re-expression of SULF1 in ESCC cell line results in the downregulation of hepatocyte growth factor-mediated activation of MAPK pathways with a resultant decrease in cell invasiveness. Cell proliferation was also inhibited in SULF1-transfected KYSE150 cells. Immunohistochemical assays reveal that SULF1 is expressed in nearly half of the human ESCC tissues but not in normal esophageal epithelial cells. SULF1 expression in human ESCC tissues is negatively correlated with tumor size and tumor invasion. CONCLUSION: This study identified that SULF1 inhibits proliferation and invasion of ESCC by decreasing heparin-binding growth factor signaling and suggested that SULF1 plays an inhibiting role in the pathogenesis of ESCC.
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Carcinoma de Células Escamosas/enzimologia , Neoplasias Esofágicas/enzimologia , Fatores de Crescimento de Fibroblastos/metabolismo , Sulfotransferases/metabolismo , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias Esofágicas/patologia , Esôfago/patologia , Feminino , Humanos , Sistema de Sinalização das MAP Quinases , Masculino , Pessoa de Meia-IdadeRESUMO
To analyze the association between non-alcoholic fatty liver disease (NAFLD) and the incidence of diabetic nephropathy in patients with type 2 diabetes, the incidence of diabetic nephropathy was assessed in 413 type 2 diabetic patients, by testing the 24 h urinary albumin excretion rate (UAER). The NAFLD was diagnosed based on patient's medical history and liver ultrasound. The difference in diabetic nephropathy incidence between patients with and without NAFLD was tested by X². Multivariate logistic regression analysis was used to assess the factors associated with diabetic nephropathy among type 2 diabetic patients. Total 363 out of 413 type 2 diabetic patients were enrolled in this study. The incidences of NAFLD and diabetic nephropathy in participants were approximately 56% (202/363) and 38% (137/363) respectively, and there was no significant difference in the prevalence of diabetic nephropathy between patients with and without NAFLD (37.1% vs. 38.5%, p = 0.787). The duration of diabetes (odds ratio [OR] 1.065, 95% confidence interval [CI] 1.014--1.120, p = 0.012), waist circumference (OR 1.077, 95% CI 1.040--1.116, p = 0.000), and fasting blood glucose (FBG; OR 1.136, 95% CI 1.023--1.1262, p = 0.017) were significantly associated with diabetic nephropathy, whereas sex, high blood pressure, total cholesterol (TC), triglyceride (TG), and ankle brachial pressure index (ABI) were not significantly associated with the disorder. The present results suggest that NAFLD is not related to the incidence of diabetic nephropathy in type 2 diabetes, but the duration of diabetes, waist circumference, and FBG are important factors for diabetic nephropathy in type 2 diabetes.
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Nefropatias Diabéticas/complicações , Nefropatias Diabéticas/epidemiologia , Hepatopatia Gordurosa não Alcoólica/complicações , Idoso , Diabetes Mellitus Tipo 2/complicações , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Estudos Retrospectivos , Fatores de RiscoRESUMO
BACKGROUND: Colorectal laterally spreading tumors (LSTs) with malignant potential require en bloc resection by endoscopic submucosal dissection (ESD), but lesions with deep submucosal invasion (SMI) are endoscopically unresectable. AIM: To investigate the factors associated with high-grade dysplasia (HGD)/carcinoma and deep SMI in colorectal LSTs. METHODS: The endoscopic and histological results of consecutive patients who underwent ESD for colorectal LSTs in our hospital from June 2013 to March 2019 were retrospectively analyzed. The characteristics of LST subtypes were compared. Risk factors for HGD/carcinoma and deep SMI (invasion depth ≥ 1000 µm) were determined using multivariate logistic regression. RESULTS: A total of 323 patients with 341 colorectal LSTs were enrolled. Among the four subtypes, non-granular pseudodepressed (NG-PD) LSTs (85.5%) had the highest rate of HGD/carcinoma, followed by the granular nodular mixed (G-NM) (77.0%), granular homogenous (29.5%), and non-granular flat elevated (24.2%) subtypes. Deep SMI occurred commonly in NG-PD LSTs (12.9%). In the adjusted multivariate analysis, NG-PD [odds ratio (OR) = 16.8, P < 0.001) and G-NM (OR = 7.8, P < 0.001) subtypes, size ≥ 2 cm (OR = 2.2, P = 0.005), and positive non-lifting sign (OR = 3.3, P = 0.024) were independently associated with HGD/carcinoma. The NG-PD subtype (OR = 13.3, P < 0.001) and rectosigmoid location (OR = 8.7, P = 0.007) were independent risk factors for deep SMI. CONCLUSION: Because of their increased risk for malignancy, it is highly recommended that NG-PD and G-NM LSTs are removed en bloc through ESD. Given their substantial risk for deep SMI, surgery needs to be considered for NG-PD LSTs located in the rectosigmoid, especially those with positive non-lifting signs.
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It has been reported that the expression of tumor suppressor gene N-myc downstream-regulated gene 2 (NDRG2) was significantly reduced in human solid tumors, including esophageal squamous cell carcinoma (ESCC). This study aimed to explore whether the difference of NDRG2 expression exists in different stages of ESCC and provides a basis for the early diagnosis and prognosis of ESCC. Immunohistochemical staining was used to investigate the expression level of NDRG2 in samples from 91 patients with mild-to-moderate dysplasia, early ESCC, and advanced ESCC. The relationship between the expression of NDRG2 and clinicopathological characteristics of the patients was analyzed. The results showed that positive expression rates of NDRG2 in tissues adjacent to early ESCC (76.7%), or from mild-to-moderate dysplasia (74.1%), and early ESCC (83.3%) were significantly higher than in tissue from advanced ESCC (55.9%). The positive expression rate in advanced ESCC was significantly lower than in the other three tissue types (p < 0.05). There was a significant difference (p < 0.05) and correlation (Cramer's V = 0.351, p = 0.019, <0.05) between the expression of NDRG2 and the clinical stage in the 64 patients with ESCC. In conclusion, this study found that the expression of NDRG2 gradually decreased with the progression of esophageal lesions into advanced ESCC. This difference in positive expression rate was more obvious in male patients and patients under 60 years of age. Therefore, the detection of NDRG2 plays an important role in differentiating early ESCC from advanced ESCC.
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Carcinogênese/metabolismo , Neoplasias Esofágicas/metabolismo , Carcinoma de Células Escamosas do Esôfago/metabolismo , Regulação Neoplásica da Expressão Gênica , Proteínas Supressoras de Tumor/biossíntese , Carcinogênese/genética , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/genética , Carcinoma de Células Escamosas do Esôfago/patologia , Feminino , Humanos , Masculino , Proteínas Supressoras de Tumor/genéticaRESUMO
OBJECTIVE: We aimed to investigate the clinical outcomes of endoscopic submucosal dissection (ESD) for the treatment of colorectal laterally spreading tumors (LSTs) and the factors related to technical difficulty. METHODS: Consecutive patients who underwent ESD for colorectal LSTs between June 2013 and January 2019 were retrospectively included. Factors associated with difficult ESD procedures (defined as conversion to piecemeal resection or discontinuation of endoscopic procedure), and dissection with a slow speed (<8 mm2 /min), were determined using the logistic regression analysis. RESULTS: A total of 325 patients with 342 colorectal LSTs (median size 20.0 mm) were enrolled. The proportions of granular (LST-G) and non-granular LST (LST-NG) were 62.9% and 37.1%, respectively. The overall en bloc and complete resection rates were 89.8% and 81.9%, respectively. The endoscopic procedure was discontinued in four lesions (1.2%), and 31 (9.1%) converted to piecemeal resection because of technical difficulty. Using multivariate analysis, positive non-lifting sign (odds ratio [OR] 19.9, P < 0.001), tumor size ≥20 mm (OR 10.0, P < 0.001), and less experienced endoscopists (OR 3.7, P = 0.005) were independent factors for technically difficult procedure. Positive non-lifting sign (OR 3.7, P = 0.004), lesion size <20 mm (OR 3.7, P < 0.001), LST-NG type (OR 1.8, P = 0.034), and less colorectal ESD experience (OR 1.9, P = 0.016) were independent factors of slow-speed dissection. CONCLUSIONS: ESD was feasible and safe for treating colorectal LSTs. Positive non-lifting sign and tumor ≥20 mm indicated difficult ESD procedures. Technical failure was more likely to occur in lesions resected by less-experienced endoscopists. Dissection speed might be improved with more experienced operators.
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Neoplasias Colorretais , Ressecção Endoscópica de Mucosa , Colonoscopia/métodos , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Ressecção Endoscópica de Mucosa/efeitos adversos , Ressecção Endoscópica de Mucosa/métodos , Humanos , Mucosa Intestinal/patologia , Mucosa Intestinal/cirurgia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
OBJECTIVES: Colorectal endoscopic submucosal dissection (ESD) is challenging because of the difficulty in adequately visualizing the submucosal layer. Many traction methods have been developed to facilitate submucosal dissection; however, they are not widely applied. Therefore, we designed a new traction device, a traction ring, and conducted this pilot study to evaluate its feasibility and safety for colorectal ESD. METHODS: Twenty patients with colorectal lesions who underwent traction ring-assisted ESD were retrospectively included. The main outcomes included en bloc resection rate, R0 resection rate, procedure time, resection time, and intraoperative and postoperative complications. RESULTS: The median procedure time was 74.5 min (range 35-269 min). The median resection time was 55 min (range 25-209 min). Application of the traction system accounted for only 2.7% of the entire procedure time. The en bloc resection rate was 95.0% (19/20), whereas the R0 resection rate was 90.0% (18/20). All traction rings were successfully set and retrieved. Significant intraoperative bleeding was not observed. One patient experienced perforation after treatment, but no further intervention was required. No delayed complications were observed within 1 month post-ESD. CONCLUSION: Traction ring is an effective and safe method for colorectal ESD and can be used at any location in the colorectum.
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Neoplasias Colorretais , Ressecção Endoscópica de Mucosa , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Ressecção Endoscópica de Mucosa/métodos , Humanos , Projetos Piloto , Estudos Retrospectivos , Tração/métodos , Resultado do TratamentoRESUMO
INTRODUCTION: The secreted frizzled-related protein 1 (SFRP1) gene, as a Wnt signaling modulator, is frequently inactivated by promoter methylation in many tumors including gastric cancer, breast cancer, oral squamous cell carcinoma, and esophageal adenocarcinoma. However, the role of SFRP1 in esophageal squamous cell carcinoma (ESCC) is not clear. In this study, we investigated the epigenetic inactivation of the SFRP1 gene in ESCC. METHODS: Nine ESCC cell lines, two immortalized human esophageal epithelial cell lines, twenty ESCC tissues, and paired adjacent nontumor tissues were analyzed in the study. Methylation-specific polymerase chain reaction (PCR), bisulfite sequencing, reverse-transcription PCR, immunohistochemistry, and chromatin immunoprecipitation assay were used to detect SFRP1 promoter methylation, expression of the SFRP1 gene, and histone modification in the SFRP1 promoter region. RESULTS: The SFRP1 promoter was found to be highly methylated in 95% (19/20) of the ESCC tissues and in nine ESCC cell lines, compared with 65% (13/20) of the paired nontumor tissues. Moreover, we confirmed that complete methylation of the SFRP1 gene promoter was correlated with its greatly reduced expression level. After individual treatment with 5-aza-2'-deoxycytidine (DAC) and trichostatin A (TSA), the messenger RNA (mRNA) level of the SFRP1 gene was not obviously rescued in the EC9706 cell line. Combined incubation with DAC and TSA can, however, substantially increase the SFRP1 mRNA expression level in the EC9706 cell line. Chromatin immunoprecipitation assay showed that acetylated histone H3 and H4 were found in the SFRP1 promoter region. CONCLUSION: Promoter hypermethylation of SFRP1 is a frequent event in ESCC. Promoter methylation and histone acetylation may cooperatively regulate expression of the SFRP1 gene.
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Carcinoma de Células Escamosas/genética , Neoplasias Esofágicas/genética , Inativação Gênica , Peptídeos e Proteínas de Sinalização Intercelular/genética , Proteínas de Membrana/genética , Antimetabólitos Antineoplásicos/farmacologia , Azacitidina/análogos & derivados , Azacitidina/farmacologia , Carcinoma de Células Escamosas/metabolismo , Linhagem Celular Tumoral/efeitos dos fármacos , Metilação de DNA , Decitabina , Neoplasias Esofágicas/metabolismo , Inibidores de Histona Desacetilases/farmacologia , Humanos , Ácidos Hidroxâmicos/farmacologia , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Proteínas de Membrana/metabolismoRESUMO
To explore the role of DNA methyltransferase 1 (DNMT1) in esophageal squamous cell carcinoma (ESCC) and the potential of DNMT1-targeted small interfering RNA as ESCC therapy, we examined expression changes of DNMT1 in ESCC and investigated the effect of DNMT1 knockdown by RNA interference in a human ESCC cell line, KYSE30. DNMT1 messenger RNA was over-expressed in seven out of 12 ESCC samples, and the percentage of cells expressing DNMT1 was significantly higher in ESCC tissues compared with paired non-cancerous tissues. DNMT1 protein levels correlated with lymph node metastasis, but exhibited no correlation with sex, age, tumor site, or tumor differentiation. Knockdown of DNMT1 in KYSE30 cells using RNA interference resulted in a reduction of promoter methylation and re-expression of methyl-guanine methyl-transferase and retinoic acid receptors beta, inhibition of cell proliferation/viability and induction of cell apoptosis. These results indicate that DNMT1 over-expression is involved in ESCC and correlated with lymph node metastasis. Knockdown of DNMT1 led to promoter demethylation and re-expression of several tumor suppressor genes thereby inhibiting cell proliferation/viability and inducing cell apoptosis.
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Carcinoma de Células Escamosas/genética , DNA (Citosina-5-)-Metiltransferases/genética , DNA (Citosina-5-)-Metiltransferases/metabolismo , Neoplasias Esofágicas/genética , Regulação Neoplásica da Expressão Gênica , RNA Mensageiro/metabolismo , Apoptose , Caderinas/genética , Caderinas/metabolismo , Carcinoma de Células Escamosas/enzimologia , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Proliferação de Células , Sobrevivência Celular , DNA (Citosina-5-)-Metiltransferase 1 , DNA (Citosina-5-)-Metiltransferases/antagonistas & inibidores , Metilação de DNA , Neoplasias Esofágicas/enzimologia , Neoplasias Esofágicas/patologia , Humanos , Metástase Linfática , O(6)-Metilguanina-DNA Metiltransferase/genética , O(6)-Metilguanina-DNA Metiltransferase/metabolismo , Regiões Promotoras Genéticas , Protocaderinas , Interferência de RNA , Receptores do Ácido Retinoico/genética , Receptores do Ácido Retinoico/metabolismo , Ubiquitina Tiolesterase/genética , Ubiquitina Tiolesterase/metabolismo , Regulação para Cima/genéticaRESUMO
OBJECTIVE: To investigate systematically previous studies on the accuracy of artificial intelligence (AI)-assisted diagnostic models in detecting esophageal neoplasms on endoscopic images so as to provide scientific evidence for the effectiveness of these models. METHODS: A literature search was conducted on the PubMed, EMBASE and Cochrane Library databases for studies on the AI-assisted detection of esophageal neoplasms on endoscopic images published up to December 2020. A bivariate mixed-effects regression model was used to calculate the pooled diagnostic efficacy of AI-assisted system. Subgroup analyses and meta-regression analyses were performed to explore the sources of heterogeneity. The effectiveness of AI-assisted models was also compared with that of the endoscopists. RESULTS: Sixteen studies were included in the systematic review and meta-analysis. The pooled sensitivity, specificity, positive and negative likelihood ratios, diagnostic odds ratio and area under the summary receiver operating characteristic curve regarding AI-assisted detection of esophageal neoplasms were 94% (95% confidence interval [CI] 92%-96%), 85% (95% CI 73%-92%), 6.40 (95% CI 3.38-12.11), 0.06 (95% CI 0.04-0.10), 98.88 (95% CI 39.45-247.87) and 0.97 (95% CI 0.95-0.98), respectively. AI-based models performed better than endoscopists in terms of the pooled sensitivity (94% [95% CI 84%-98%] vs 82% [95% CI 77%-86%, P < 0.01). CONCLUSIONS: The use of AI results in increased accuracy in detecting early esophageal cancer. However, most of the included studies have a retrospective study design, thus further validation with prospective trials is required.
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Inteligência Artificial , Neoplasias Esofágicas , Endoscopia , Neoplasias Esofágicas/diagnóstico , Humanos , Estudos Prospectivos , Estudos Retrospectivos , Sensibilidade e EspecificidadeRESUMO
OBJECTIVE: We aimed to establish a standardized procedure for white light gastroscopy (WLG) to screen gastric lesions including early gastric cancer (EGC) in China and to verify its efficacy and feasibility in clinical practice. METHODS: A standardized WLG procedure for outpatients at nine tertiary hospitals in Beijing was established. Clinical information of the participants and details of the endoscopic procedures were recorded. RESULTS: A total of 1051 participants were enrolled in a baseline conventional endoscopic survey between March 2014 and December 2015, while 2156 patients were enrolled in the standardized WLG operation from January 2016 to June 2017. The procedure time of the standardized procedure was significantly longer than that of the baseline conventional procedure (P = 0.003). More images were obtained during the standardized procedure compared with the baseline conventional procedure (P < 0.001). The overall detection rate of gastric lesions in the standardized procedure group was significantly higher than that in the baseline procedure group (52.5% vs 38.4%, P < 0.01). The satisfaction scores of both participants and endoscopists in the standardized procedure group were significantly higher than in the baseline procedure group. CONCLUSIONS: Compared with the conventional procedure, standardized WLG procedure significantly improves the detection rate of gastric lesions as well as the satisfaction score of participants and endoscopists despite its longer procedure time. It is effective and feasible in clinical practice in China for the use of currently available endoscopic equipment.
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Gastroscopia , Neoplasias Gástricas , China , Detecção Precoce de Câncer , Estudos de Viabilidade , Humanos , Neoplasias Gástricas/diagnósticoRESUMO
OBJECTIVE: To evaluate the effect of ilaprazole enteric tablets on intragastric pH in duodenal ulcer patients. METHODS: A randomized, double blind, positive controlled clinical trial was carried out. A total of forty-two patients with duodenal ulcer were randomized into low dose ilaprazole group (5 mg/d), medium dose ilaprazole group (10 mg/d), high dose ilaprazole group (20 mg/d) and omeprazole group (20 mg/d). An ambulatory 24 hour intragastric pH study was performed at the fifth treatment day. Fraction time pH above 3, 4 or 5, median values of 24 hour diurnal pH and 12 hour nocturnal pH, the percentage of patients with total time pH above 3, 4 or 5 at least for 18 hours were evaluated. RESULTS: There were no significant differences of fraction time pH above 3 or 4, median values of 24 hour diurnal pH and 12 hour nocturnal pH and the percentage of patients with total time pH above 3, 4 or 5 at least for 18 hours among all the groups with different doses of ilaprazole and the omeprazole group. The fraction time pH above 5 in medium and high dose ilaprazole groups were (87.96 + or - 12.29)% and (89.86 + or - 15.18)% respectively, which was higher than that in low dose ilaprazole group [(67.17 + or - 30.16)%] and omeprazole group [(76.14 + or - 16.75)%], P < 0.05. CONCLUSION: Ilaprazole has a strong effect on intragastric acid control with a dose dependent trend.
Assuntos
Benzimidazóis/uso terapêutico , Úlcera Duodenal/tratamento farmacológico , Inibidores da Bomba de Prótons/uso terapêutico , Estômago/fisiopatologia , Sulfóxidos/uso terapêutico , 2-Piridinilmetilsulfinilbenzimidazóis , Adulto , Antiulcerosos/uso terapêutico , Método Duplo-Cego , Úlcera Duodenal/fisiopatologia , Feminino , Humanos , Concentração de Íons de Hidrogênio , Masculino , Pessoa de Meia-Idade , Omeprazol/uso terapêutico , Adulto JovemRESUMO
Endoscopic drainage of pancreatic fluid collections (PFCs) with fewer complications and less trauma has gradually replaced surgery or percutaneous drainage to become the first-line treatment for PFCs. In recent years, the differential efficacy of various stent techniques to drain different types of PFCs has been controversial. This review summarizes the clinical applications of endoscopic ultrasound-guided stent placement for PFCs drainage.
RESUMO
OBJECTIVE: To investigate the effectiveness and safety of transparent cap-assisted endoscopy in removing foreign bodies in the esophagus. METHODS: Patients with foreign body lodged in the esophagus who received a transparent cap-assisted or conventional endoscopy between October 2004 and July 2018 were retrospectively enrolled. Propensity score matching was performed. The success rate of the endoscopic procedure, procedure time, clearness of endoscopic view and adverse event rate were compared between the two groups. RESULTS: Of the 838 patients who had a foreign body lodged in the esophagus, 728 (86.9%) underwent endoscopic intervention. After matched by prospensity score, 224 patients each received either transparent cap-assisted endoscopy or conventional endoscopy. No difference was noted between the two groups in terms of the success rate (100% vs 99.1%, P = 0.499). Transparent cap-assisted endoscopy was associated with shorter procedure time for removing jujube pits ([4.24 ± 2.81] min vs [7.62 ± 8.15] min, P = 0.001), fish bones ([2.99 ± 2.15] min vs [6.49 ± 6.54] min, P < 0.001) and other sharp objects ([4.29 ± 3.36] min vs [10.60 ± 19.79 min], P = 0.027) and higher rates of clear endoscopic views in extracting jujube pits, fish bones, poultry bones and other sharp objects (98% vs 43.4%, 97.5% vs 74.1%, 100% vs 81.3% and 100% vs 82.7%; all P < 0.05). No significant differences in the rates of adverse event were observed between the groups (P = 1.000). CONCLUSION: Transparent cap-assisted endoscopic technique is effective and safe for removing sharp foreign bodies in the esophagus.