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Nucleic acids, because of their precise pairing and simple composition, have emerged as excellent materials for the formation of gels. The application of DNA hydrogels in the diagnosis and therapy of cancer has expanded significantly through research on the properties and functions of nucleic acids. Functional nucleic acids (FNAs) such as aptamers, Small interfering RNA (siRNA), and DNAzymes have been incorporated into DNA hydrogels to enhance their diagnostic and therapeutic capabilities. This review discusses various methods for forming DNA hydrogels, with a focus on pure DNA hydrogels. We then explore the innovative applications of DNA hydrogels in cancer diagnosis and therapy. DNA hydrogels have become essential biomedical materials, and this review provides an overview of current research findings and the status of DNA hydrogels in the diagnosis and therapy of cancer, while also exploring future research directions.
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INTRODUCTION: This study aimed to investigate the prevalence of disorders of gut-brain interaction (DGBI) and life stress in college students, and explore risk factors of DGBI in college students and the role of life stress. METHODS: A total of 2,578 college students filled up validated questionnaires assessing GI symptoms, lifestyle, and life stress. Participants were diagnosed as DGBI based on the Rome III criteria. Multivariate ordinal logistic regression analysis and mediation effect model were employed to explore potential risk factors of DGBI and the mediating role of life stress and lifestyle in DGBI. RESULTS: A total of 437 of 2,578 (17.0%) college students were diagnosed with DGBI. College students with DGBI had higher levels of life stress, including eight specific categories. Females (1.709 [1.437, 2.033]), staying up late (1.519 [1.300, 1.776]), and life stress (1.008 [1.006, 1.010]) were risk factors for DGBI, while postgraduates (0.751 [0.578, 0.976]) and regular diet (0.751 [0.685, 0.947]) were protective factors. Males and poor family economic were associated with a higher risk of DGBI after controlling stress, while an association between grade and DGBI was mediated by stress, regular diet, and sleep habits. CONCLUSION: DGBI was common among college students. Life stress and lifestyle were associated with DGBI and mediated partial association between grade and DGBI in college students. More attention should be paid to undergraduates.
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Helicobacter pylori eradication is crucial in the treatment of peptic ulcers caused by H. pylori infection, a disease highly prevalent in Asia. We present a pooled analysis of two randomized, double-blind, double-dummy, phase 3 studies evaluating the efficacy and safety of vonoprazan-based bismuth-containing quadruple therapy for H. pylori eradication. Patients aged ≥18 years with endoscopically confirmed duodenal or gastric ulcers were randomized 1 : 1 to receive vonoprazan 20 mg or lansoprazole 30 mg once daily for up to 6 (duodenal ulcers) or 8 weeks (gastric ulcers). H. pylori-positive patients received vonoprazan- or lansoprazole-based bismuth-containing quadruple therapy for the first 2 weeks. H. pylori eradication was determined using the carbon-13 urea breath test at a follow-up visit 4 weeks post-treatment. The H. pylori eradication rate was 90.6% with vonoprazan vs. 85.2% with lansoprazole (difference: 5.4%; 95% confidence interval (CI): -0.1, 10.8). H. pylori eradication rates were 7.1% (95% CI: 1.4, 12.8) and 12.6% (95% CI: 3.9, 22.0) higher in patients aged <65 years and current smokers, respectively, with vonoprazan vs. lansoprazole. In the Chinese subpopulation, the H. pylori eradication rate was 92.0% with vonoprazan vs. 86.0% with lansoprazole (difference: 6.1%; 95% CI: 0.5, 11.7). Treatment-emergent adverse events occurred in 72.7 vs. 62.6% of H. pylori-positive patients at baseline in the vonoprazan vs. lansoprazole arm. H. pylori eradication with vonoprazan-based quadruple therapy was noninferior to lansoprazole-based quadruple therapy and exceeded 90%, a clinically relevant threshold for determining the efficacy of H. pylori eradication regimens (ClinicalTrials.gov identifier: NCT03050359; NCT03050307).
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Antibacterianos , Quimioterapia Combinada , Infecções por Helicobacter , Helicobacter pylori , Lansoprazol , Úlcera Péptica , Inibidores da Bomba de Prótons , Pirróis , Sulfonamidas , Humanos , Pirróis/efeitos adversos , Pirróis/uso terapêutico , Pirróis/administração & dosagem , Sulfonamidas/uso terapêutico , Sulfonamidas/efeitos adversos , Sulfonamidas/administração & dosagem , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/microbiologia , Helicobacter pylori/efeitos dos fármacos , Pessoa de Meia-Idade , Masculino , Feminino , Método Duplo-Cego , Lansoprazol/uso terapêutico , Lansoprazol/administração & dosagem , Lansoprazol/efeitos adversos , Adulto , Antibacterianos/efeitos adversos , Antibacterianos/uso terapêutico , Antibacterianos/administração & dosagem , Inibidores da Bomba de Prótons/uso terapêutico , Inibidores da Bomba de Prótons/efeitos adversos , Inibidores da Bomba de Prótons/administração & dosagem , Úlcera Péptica/tratamento farmacológico , Úlcera Péptica/microbiologia , Idoso , Antiulcerosos/uso terapêutico , Antiulcerosos/administração & dosagem , Antiulcerosos/efeitos adversos , Resultado do Tratamento , Testes RespiratóriosRESUMO
INTRODUCTION: The therapeutic effect of probiotics for irritable bowel syndrome (IBS) was controversial. This study aims to evaluate the short-term efficacy of Bifidobacterium quadruple viable tablet in patients with diarrhea-predominant IBS and explore factors associated with response to probiotics. METHODS: A randomized, double-blind, placebo-controlled, multicenter trial was performed in 15 hospitals. A total of 290 patients who fulfilled the eligibility criteria were assigned to the probiotics or placebo group randomly with a ratio of 1:1 for a 4-week treatment and a 2-week follow-up. The primary outcome was the response rate. It was regarded as the proportion of patients with composite responses of improvement in both abdominal pain and diarrhea simultaneously. RESULTS: After 4-week continuous administration, the response rates of the probiotics and the placebo were 67.59% and 36.55%, respectively ( P < 0.001). In the probiotics, those with higher abdominal pain scores (2.674 [1.139-6.279]) were more likely to respond, but responders in placebo had lower Hamilton Depression Scale score (0.162 [0.060-0.439]), lower Hamilton Anxiety Scale score (0.335 [0.148-0.755]), and higher degree of bloating (2.718 [1.217-6.074]). Although the diversity of the microbiota was not significantly changed by probiotics, the abundance of bacteria producing short-chain fatty acids (SCFAs), including Butyricimonas ( P = 0.048), Pseudobutyrivibrio ( P = 0.005), Barnesiella ( P = 0.020), and Sutterella ( P = 0.020), and the concentration of SCFAs including butyric acid ( P = 0.010), valeric acid ( P = 0.019), and caproic acid ( P = 0.046) in feces increased. DISCUSSION: A Bifidobacterium quadruple viable tablet had a significant short-term efficacy for the treatment of diarrhea-predominant IBS and was more effective in patients with higher abdominal pain scores. This kind of probiotics could improve the abundance of several bacteria producing SCFAs and the concentration of fecal SCFAs compared with placebos.
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Síndrome do Intestino Irritável , Probióticos , Humanos , Síndrome do Intestino Irritável/terapia , Síndrome do Intestino Irritável/tratamento farmacológico , Bifidobacterium , Diarreia/terapia , Diarreia/complicações , Fezes/microbiologia , Dor Abdominal/etiologia , Dor Abdominal/terapia , Probióticos/uso terapêutico , Método Duplo-Cego , Resultado do TratamentoRESUMO
BACKGROUND: Our previous study showed that fucosyltransferase 2 (Fut2) deficiency is closely related to colitis. Colitis increases the risk for the development of colorectal cancer (CRC). This study aimed to investigate the effect and underlying mechanism of action of Fut2 in CRC. METHODS: Intestinal epithelium-specific Fut2 knockout (Fut2â³IEC) mice were used in this study. CRC was induced using azoxymethane (AOM) and dextran sulfate sodium (DSS). Immunofluorescence was used to examine the fucosylation levels. Proteomics and N-glycoproteomics analyses, Ulex Europaeus Agglutinin I (UEA-I) affinity chromatography, immunoprecipitation, and rescue assay were used to investigate the mechanism of Fut2 in CRC. RESULTS: The expression of Fut2 and α-1,2-fucosylation was lower in colorectal tumor tissues than in the adjacent normal tissues of AOM/DSS-induced CRC mice. More colorectal tumors were detected in Fut2â³IEC mice than in control mice, and significant downregulation of melanoma cell adhesion molecule (MCAM) fucosylation was detected in the colorectal tumor tissues of Fut2â³IEC mice. Overexpression of Fut2 inhibited cell proliferation, invasion and tumor metastasis in vivo and in vitro in SW480 and HCT116 cells. Moreover, fucosylation of MCAM may be a mediator of Fut2 in CRC. Peracetylated 2-F-Fuc, a fucosyltransferase inhibitor, repressed fucosylation modification of MCAM and reversed the inhibitory effects of Fut2 overexpression on SW480 cell proliferation, migration, and invasion. Our results indicate that Fut2 deficiency in the intestinal epithelium promotes CRC by downregulating the fucosylation of MCAM. CONCLUSIONS: The regulation of fucosylation may be an potential therapy for CRC, especially in patients with Fut2 gene defects.
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Colite , Neoplasias Colorretais , Animais , Camundongos , Colite/induzido quimicamente , Neoplasias Colorretais/patologia , Sulfato de Dextrana/efeitos adversos , Fucosiltransferases/genética , Fucosiltransferases/metabolismo , Mucosa Intestinal/patologia , Galactosídeo 2-alfa-L-FucosiltransferaseRESUMO
Maintenance of internal homeostasis is a sophisticated process, during which almost all organs get involved. Liver plays a central role in metabolism and involves in endocrine, immunity, detoxification and storage, and therefore it communicates with distant organs through such mechanisms to regulate pathophysiological processes. Dysfunctional liver is often accompanied by pathological phenotypes of distant organs, including the eyes. Many reviews have focused on crosstalk between the liver and gut, the liver and brain, the liver and heart, the liver and kidney, but with no attention paid to the liver and eyes. In this review, we summarized intimate connections between the liver and the eyes from three aspects. Epidemiologically, we suggest liver-related, potential, protective and risk factors for typical eye disease as well as eye indicators connected with liver status. For molecular mechanism aspect, we elaborate their inter-organ crosstalk from metabolism (glucose, lipid, proteins, vitamin, and mineral), detoxification (ammonia and bilirubin), and immunity (complement and inflammation regulation) aspect. In clinical application part, we emphasize the latest advances in utilizing the liver-eye axis in disease diagnosis and therapy, involving artificial intelligence-deep learning-based novel diagnostic tools for detecting liver disease and adeno-associated viral vector-based gene therapy method for curing blinding eye disease. We aim to focus on and provide novel insights into liver and eyes communications and help resolve existed clinically significant issues.
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Oftalmopatias , Hepatopatias , Humanos , Inteligência Artificial , InflamaçãoRESUMO
BACKGROUND: Rifaximin has been increasingly applied in irritable bowel syndrome (IBS) treatment. Whether there were differences in the effects of rifaximin on microbiota from different intestinal segments, especially the small intestine where rifaximin predominantly acted, has not been confirmed. METHODS: In this study, we used Trichinella spiralis infection to induce post infectious irritable bowel syndrome (PI-IBS) and measured visceral sensitivity of mice by means of abdominal withdrawal reflex (AWR) tests to colorectal distention (CRD). We compared the effects of rifaximin on the composition of ileal, colonic mucosal and fecal microbiota in PI-IBS mice. RESULTS: Rifaximin significantly reduced AWR scores and increased pain threshold in PI-IBS mice, and this effect was associated with the change in the relative abundance of ileal mucosal microbiota. Rifaximin could obviously decrease ileum mucosal microbiota alpha diversity assessed by Shannon microbial diversity index. Meanwhile, the analysis of beta diversity and relative abundance of microbiota at phylum, family and genus levels showed that rifaximin could improve the microbiota structure of ileal mucosa. However, for colonic mucosal and fecal microbiota, this effect of rifaximin was not obvious. Rifaximin could reshape the correlation of genera between different intestinal segments. CONCLUSION: Rifaximin improved visceral hypersensitivity in PI-IBS mice. Rifaximin mainly affected ileal mucosal microbiota, and its improvement effect on IBS might be closely related to the improvement of ileal microbiota structure.
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Síndrome do Intestino Irritável , Microbiota , Camundongos , Animais , Síndrome do Intestino Irritável/tratamento farmacológico , Rifaximina/farmacologia , Intestinos , Mucosa IntestinalRESUMO
COVID-19 is characterized by a predominantly prothrombotic state, which underlies severe disease and poor outcomes. Imbalances of the gut microbiome have been linked with abnormal hemostatic processes. Understanding the relationship between the gut microbiome and abnormal coagulation parameters in COVID-19 could provide a novel framework for the diagnosis and management of COVID-related coagulopathies (CRC). This cross-sectional study used shotgun metagenomic sequencing to examine the gut microbiota of patients with CRC (n = 66) and compared it to COVID control (CCs) (n = 27) and non-COVID control (NCs) (n = 22) groups. Three, 1, and 3 taxa were found enriched in CRCs, CCs, and NCs. Next, random forest models using 7 microbial biomarkers and differential clinical characteristics were constructed and achieved strong diagnostic potential in distinguishing CRC. Specifically, the most promising biomarker species for CRC were Streptococcus thermophilus, Enterococcus faecium, and Citrobacter portucalensis. Conversely, Enterobacteriaceae family and Fusicatenibacter genus are potentially protective against CRC in COVID patients. We further identified 4 species contributing to 20 MetaCyc pathways that were differentially abundant among groups, with S. thermophilus as the main coding species in CRCs. Our findings suggest that the alterations of gut microbiota compositional and functional profiles may influence the pathogenesis of CRC and that microbiota-based diagnosis and treatment could potentially benefit COVID patients in preventing and alleviating thrombosis-related clinical outcomes.
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Transtornos da Coagulação Sanguínea , COVID-19 , Microbioma Gastrointestinal , Microbiota , Humanos , Estudos Transversais , COVID-19/complicações , Transtornos da Coagulação Sanguínea/etiologiaRESUMO
OBJECTIVE: Little is known about association between the efficacy of probiotics and baseline gut microbiota in irritable bowel syndrome (IBS). We aimed to explore gut microbiota in diarrhea-predominant IBS (IBS-D) and whether baseline gut microbiota was related to the efficacy of Bacillus subtilis and Enterococcus faecium (BE). METHODS: This study recruited 19 healthy controls (HC) and 50 IBS-D patients, among whom 19 patients were administrated 500 mg BE orally three times daily for 2 weeks. Clinical data and fecal samples were collected from patients before and after treatment. 16S rRNA sequencing was performed to obtain fecal bacterial data. RESULTS: There was no significant difference of alpha diversity, beta diversity, profiles of microbial phyla and genera between HC and IBS. BE improved IBS-SSS (IBS severity scoring system) and stool consistency, and altered Enterococcus, Blautia, Lachnoclostridium and Fusobacterium without significant impact on microbial structure in IBS-D. Notably, baseline fecal bacterial composition differed between non-responders and responders to BE concerning abdominal pain and bloating, with Atopobium, Pyramidobacter, Ruminococcus gnavus and Peptostreptococcus enriched in responders in terms of abdominal pain. There was reduced abundance of Prevotella, Ruminococcaceae UCG, Eubacterium eligens, Faecalibacterium and Eubacterium coprostanoligenes in responders compared with non-responders. Furthermore, BE increased beneficial bacteria including Faecalibacterium, Blautia and Butyricicoccus, decreased Lachnoclostridium and Bilophila, and influenced some microbial metabolic pathways in responders, such as mineral absorption, metabolism of arachidonic acid, d-arginine, D-ornithine, phenylalanine and vitamin B6. CONCLUSION: Baseline fecal microbiome is associated with the efficacy of BE in attenuating abdominal pain and bloating in IBS-D.
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Enterococcus faecium , Microbioma Gastrointestinal , Síndrome do Intestino Irritável , Humanos , Síndrome do Intestino Irritável/complicações , Diarreia/microbiologia , Enterococcus faecium/genética , Bacillus subtilis/genética , Microbioma Gastrointestinal/genética , RNA Ribossômico 16S/análise , Fezes/química , Dor AbdominalRESUMO
Alcohol-mediated reactive oxygen species (ROS) play a vital role in intestinal barrier injury. However, the mechanism of ROS accumulation in enterocytes needs to be explored further. In our study, we found that chronic-binge ethanol-fed mice had increased levels of gut oxidative stress and high intestinal permeability. The transcription profiles of the colonic epithelial cells showed that the level of NADPH oxidase 1 (NOX1) was significantly elevated in alcohol-exposed mice compared with isocaloric-exposed mice. In vitro, NOX1 silencing alleviated ROS accumulation and the apoptosis of human colonic epithelial cells (NCM460), while NOX1 overexpression accelerated oxidative stress injury of NCM460 cells. Propionic acid was reduced in the gut of chronic-binge ethanol-fed mice, compared with isocaloric-fed mice, as observed through untargeted metabolomic analysis. Supplementation with propionate relieved ethanol-induced liver and intestinal barrier injuries and reduced the level of ROS accumulation and apoptosis of ethanol-induced colonic epithelial cells. Propionate alleviating NOX1 induced ROS injury of colonic epithelial cells, independent of G protein-coupled receptors. Propionate significantly inhibited histone deacetylase 2 (HDAC2) expressions both in ethanol-exposed colonic epithelial cells and TNF-α-treated NCM460. Chromatin immunoprecipitation (ChIP) assays showed that propionate suppressed the NOX1 expression by regulating histone acetylation in the gene promoter region. In conclusion, NOX1 induces oxidative stress injury of colonic epithelial cells in alcohol-related liver disease. Propionate, which can act as an endogenous HDAC2 inhibitor, can decrease levels of apoptosis of intestinal epithelial cells caused by oxidative stress.
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Etanol , NADPH Oxidase 1 , Estresse Oxidativo , Animais , Humanos , Camundongos , Células Epiteliais/metabolismo , Etanol/toxicidade , Etanol/metabolismo , NADPH Oxidase 1/genética , NADPH Oxidase 1/metabolismo , Propionatos/farmacologia , Espécies Reativas de Oxigênio/metabolismoRESUMO
PURPOSE: Identifying the onset age of cancer is essential for its early intervention. The aim of this study was to characterize the features and investigate the variation tendency of first primary colorectal cancer (CRC) onset age in the USA. METHODS: For this retrospective population-based cohort analysis, data on patients diagnosed with first primary CRC (n = 330,977) between 1992 and 2017 were obtained from the Surveillance, Epidemiology, and End Results dataset. Annual percent changes (APC) and average APCs were calculated to examine the changes in average age at CRC diagnosis using the Joinpoint Regression Program. RESULTS: From 1992 to 2017, the average age at CRC diagnosis decreased from 67.0 to 61.2 years, declining by 0.22% and 0.45% annually before and after 2000. The age at diagnosis was lower in the distal than in the proximal CRC cases and the age has the downward trends in all subgroups of sex, race, and stage. Over one-fifth of CRC patients were initially diagnosed with distantly metastatic CRC, with the age lower than that in localized CRC cases (63.5 vs 64.8 years). CONCLUSIONS: The first primary CRC onset age has decreased significantly in the USA over the last 25 years and the modern lifestyle may be responsible for the decline. Specifically, the age of proximal CRC is invariably higher than that of distal CRC. Moreover, the age of advanced stage is lower than that of the early stage. Clinicians should adopt earlier screening age and more effective screening techniques for CRC.
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Neoplasias do Colo , Neoplasias Colorretais , Humanos , Estados Unidos/epidemiologia , Pessoa de Meia-Idade , Adulto , Idade de Início , Estudos Retrospectivos , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/patologia , Estudos de Coortes , IncidênciaRESUMO
Contemporary systems for the diagnosis and management gastrointestinal symptoms not attributable to organic diseases (Functional GI Disorders, FGID, now renamed Disorders of Gut-Brain Interaction, DGBI) seek to categorize patients into narrowly defined symptom-based sub-classes to enable targeted treatment of patient cohorts with similar underlying putative pathophysiology. However, an overlap of symptom categories frequently occurs and has a negative impact on treatment outcomes. There is a lack of guidance on their management. An Asian Pacific Association of Gastroenterology (APAGE) working group was set up to develop clinical practice guidelines for management of patients with functional dyspepsia (FD) who have an overlap with another functional gastrointestinal disorder: FD with gastroesophageal reflux (FD-GERD), epigastric pain syndrome with irritable bowel syndrome (EPS-IBS), postprandial distress syndrome with IBS (PDS-IBS), and FD-Constipation. We identified putative pathophysiology to provide a basis for treatment recommendations. A management algorithm is presented to guide primary and secondary care clinicians.
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Dispepsia , Refluxo Gastroesofágico , Gastroenteropatias , Síndrome do Intestino Irritável , Humanos , Dispepsia/diagnóstico , Síndrome do Intestino Irritável/diagnóstico , Gastroenteropatias/complicações , Constipação Intestinal/complicações , ÁsiaRESUMO
Drug-induced liver injury (DILI) is caused by various drugs with complex pathogenesis, and diverse clinical and pathological phenotypes. Drugs damage the liver directly through drug hepatotoxicity, or indirectly through drug-mediated oxidative stress, immune injury and inflammatory insult, which eventually lead to hepatocyte necrosis. Recent studies have found that the composition, relative content and distribution of gut microbiota in patients and animal models of DILI have changed significantly. It has been confirmed that gut microbial dysbiosis brings about intestinal barrier destruction and microorganisms translocation, and the alteration of microbial metabolites may cause or aggravate DILI. In addition, antibiotics, probiotics, and fecal microbiota transplantation are all emerging as prospective therapeutic methods for DILI by regulating the gut microbiota. In this review, we discussed how the altered gut microbiota participates in DILI.
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Doença Hepática Induzida por Substâncias e Drogas , Microbioma Gastrointestinal , Hepatopatias , Probióticos , Animais , Humanos , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/terapia , Transplante de Microbiota Fecal , Disbiose , Probióticos/uso terapêuticoRESUMO
Piezo1, a non-selective cation channel directly activated by mechanical forces, is widely expressed in the digestive system and participates in biological functions physiologically and pathologically. In this review, we summarized the latest insights on Piezo1's cellular effect across the entire digestive system, and discussed the role of Piezo1 in various aspects including ingestion and digestion, material metabolism, enteric nervous system, intestinal barrier, and inflammatory response within digestive system. The goal of this comprehensive review is to provide a solid foundation for future research about Piezo1 in digestive system physiologically and pathologically.
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Sistema Digestório , Sistema Nervoso Entérico , Canais Iônicos , Humanos , Canais Iônicos/metabolismo , Sistema Digestório/metabolismo , Mecanotransdução Celular , AnimaisRESUMO
Mucus secreted by goblet cells (GCs) may play an important role in intestinal transit function. Our previous study found that Piezo1 protein is essential for GC function; however, the effect of GC Piezo1 on intestinal transit function is unclear. Our study aimed to investigate the effect of Piezo1 in GCs on intestinal transit and the potential mechanism. We compared intestinal mucus, fecal form, intestinal transit time, intestinal epithelial cell composition, and stem cell function in WT and GC-specific Piezo1-deficient (Piezo1ΔGC) mice. Our results revealed a correlation between mucus and intestinal transit: the less mucus there was, the slower the intestinal transit. Piezo1 deficiency in GCs led to decreased mucus synthesis and also disrupted the ecological niche of colon stem cells (CSCs). Through organoid culture, we found that the capacity of proliferation and differentiation in Piezo1ΔGC mouse CSCs was significantly decreased, which also led to a reduced source of GCs. Further studies found that the reduced Wnt and Notch signals in colon crypts might be the potential mechanism. These results indicated the importance of GC Piezo1 in intestinal transit function, which acts by maintaining the homeostasis of intestinal epithelial cells and mucus.
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BACKGROUND: Heterotopic gastric mucosa in the upper oesophagus (HGMUE) was considered as geneogenous manifestation. However, its clinical characteristics may be beyond our knowledge if we focus on its extra-oesophageal presentation. So the aim of this study was to investigate the relationship between HGMUE and laryngopharyngeal symptoms. METHOD: Eight hundred and eleven patients who had gastric endoscopy examination were enrolled in this study and the cervical oesophagus was examined for the patch during withdrawal of the endoscope. Questionnaire for gastroesophageal reflux disease (GERD-Q) and Reflux Symptom Index (RSI) were completed by all the patients. Pathology feature and therapeutic effect of HGMUE patients were evaluated. RESULT: About 34.53% of the patients undergoing the gastroduodenoscopy had laryngopharyngeal (LP) symptoms. The relevance rate of HGMUE in LP(+) group (10.69%) was higher than that in LP(-) group (2%). The LP symptoms were related to the histological type and expression of H+-K+-ATPase in the histological sample of HGMUE patients. The positive rate of H+-K+-ATPase was 100% in LP(+) group, and that in LP(-) group was 28.6%. PPI therapy was effective for improving the LP symptoms in HGMUE patients. The RSI score in LP(+) patients decreased from 8.12 ± 1.46 at baseline to 4 ± 0.74 at the end of 8 weeks after treatment of PPI. CONCLUSION: HGMUE was an important cause of LP symptoms in patients, especially in those who had no evidence of GERD. The mechanism of HGMUE-induced LP symptoms was due to its location and the function of acid secretion according to the endoscopic finding and histologic characteristics.
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Doenças do Esôfago , Refluxo Gastroesofágico , Refluxo Laringofaríngeo , Humanos , Doenças do Esôfago/diagnóstico , Doenças do Esôfago/patologia , Mucosa Gástrica/patologia , Gastroscopia , Adenosina Trifosfatases , Refluxo Laringofaríngeo/diagnósticoRESUMO
OBJECTIVE: Helicobacter pylori infection is mostly a family-based infectious disease. To facilitate its prevention and management, a national consensus meeting was held to review current evidence and propose strategies for population-wide and family-based H. pylori infection control and management to reduce the related disease burden. METHODS: Fifty-seven experts from 41 major universities and institutions in 20 provinces/regions of mainland China were invited to review evidence and modify statements using Delphi process and grading of recommendations assessment, development and evaluation system. The consensus level was defined as ≥80% for agreement on the proposed statements. RESULTS: Experts discussed and modified the original 23 statements on family-based H. pylori infection transmission, control and management, and reached consensus on 16 statements. The final report consists of three parts: (1) H. pylori infection and transmission among family members, (2) prevention and management of H. pylori infection in children and elderly people within households, and (3) strategies for prevention and management of H. pylori infection for family members. In addition to the 'test-and-treat' and 'screen-and-treat' strategies, this consensus also introduced a novel third 'family-based H. pylori infection control and management' strategy to prevent its intrafamilial transmission and development of related diseases. CONCLUSION: H. pylori is transmissible from person to person, and among family members. A family-based H. pylori prevention and eradication strategy would be a suitable approach to prevent its intra-familial transmission and related diseases. The notion and practice would be beneficial not only for Chinese residents but also valuable as a reference for other highly infected areas.
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Saúde da Família , Infecções por Helicobacter/prevenção & controle , Helicobacter pylori , Controle de Infecções/organização & administração , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , China , Consenso , Técnica Delphi , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/transmissão , Humanos , Lactente , Pessoa de Meia-Idade , Adulto JovemRESUMO
Cholangiocyte death accompanied by the progression of primary biliary cholangitis (PBC) has not yet been thoroughly investigated. Thus, we are aimed to explore the role of HSP90 and a potential treatment strategy in cholangiocyte necroptosis. First, we detected the expression of HSP90 and necroptotic markers in liver tissues from patients and mice with PBC by immunohistochemistry (IHC) and real-time polymerase chain reaction (PCR). Then, the HSP90 inhibitor, 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG), was administered by intraperitoneal injection to evaluate its therapeutic effect for PBC by IHC, real-time PCR, and western blotting. Human intrahepatic bile duct epithelial cells (HIBECs) were induced to necroptosis by toxic bile acid and lipopolysaccharide (LPS) treatment, and evaluated via Cell Counting Kit-8 and flow cytometry assays. Additionally, 17-DMAG, cycloheximide, and a proteasome inhibitor were used to evaluate the role of HSP90 in cholangiocyte necroptosis. We found that the expression of HSP90 was elevated in the cholangiocytes of patients and mice with PBC, along with higher expressions of receptor-interacting serine/threonine-protein kinase 1 (RIPK1), RIPK3, mixed lineage kinase domain-like protein (MLKL), and phosphorylated-MLKL (p-MLKL). Proinflammatory cytokines and antibody levels of the E2 subunit of pyruvate dehydrogenase complex decreased after treatment with 17-DMAG in PBC mice. Meanwhile, RIPK1, RIPK3, phosphorylated-RIPK3, MLKL, and p-MLKL protein expressions decreased with 17-DMAG treatment. In vitro, 17-DMAG and necrostatin-1 prevented glycochenodeoxycholic acid and LPS-induced necroptosis of HIBECs. Immunoprecipitation and high-performance liquid chromatography-mass spectrometry analysis showed that RIPK1 combined with HSP90. Additionally, the 17-DMAG treatment reduced the RIPK1 half-life. Overall, 17-DMAG might be a potential therapeutic agent for PBC via cholangiocyte necroptosis prevention by accelerating RIPK1 degradation.
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Cirrose Hepática Biliar , Necroptose , Humanos , Animais , Camundongos , Lipopolissacarídeos/toxicidade , Proteínas Quinases/metabolismo , Proteínas de Choque Térmico HSP90 , Células Epiteliais/metabolismoRESUMO
Recently, the coronavirus disease 2019 (COVID-19) has caused a global pandemic. Several studies indicate that the digestive system can also be affected by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Therefore, patients with digestive symptoms should have a capsule endoscopy (CE). COVID-19 patients with gastrointestinal (GI) symptoms who underwent CE were recruited from March 2020 to April 2020. We collected patients' data and performed a prospective follow-up study for 6 months. All 11 COVID-19 cases with GI symptoms who underwent CE presented gastritis. Eight cases (72.7%) had intestinal mucosa inflammation. Among them, two cases showed intestinal ulcers or erosions. Moreover, two cases displayed colonic mucositis. One case was lost during follow-up. At 3-6 months after hospital discharge, five patients underwent CE again, presenting gastrointestinal lesions. Five of the 10 cases had GI symptoms, such as abdominal pain, diarrhea, constipation, and others. Among these five cases, the GI symptoms of three patients disappeared at the last follow-up and two patients still presented diarrhea symptoms. Overall, we observed damaged digestive tract mucosa that could be caused by SARS-CoV-2. Moreover, after discharge, some patients still presented intestinal lesions and GI symptoms.
Assuntos
COVID-19/complicações , COVID-19/patologia , Endoscopia por Cápsula , Gastroenteropatias/diagnóstico , Trato Gastrointestinal/patologia , Adulto , Idoso , Feminino , Seguimentos , Gastrite/complicações , Gastrite/diagnóstico , Gastrite/patologia , Gastroenteropatias/complicações , Gastroenteropatias/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
FUT2, a protein that uses l-fucose to mediate fucosylation of intestinal epithelial cells, is one of the detected gene variants in IBD patients. We aimed to investigate whether exogenous l-fucose could be an enteral nutritional supplement to protect intestinal barrier function. The effect of l-fucose on the restoration of epithelial barrier function in both the DSS-induced colitis mouse model and LPS-stimulated Caco-2 cells was investigated, and the impact on fucosylation of epithelial cells was examined. The severity of DSS-induced colitis was significantly reduced by l-fucose. Restoration of epithelial barrier function by l-fucose was detected. Direct l-fucose-mediated protection of tight junctions was observed in Caco-2 cells. Moreover, exogenous l-fucose promoted the exogenous metabolic pathway of l-fucose, and fucosylation of epithelial cells both in vivo and in vitro. Moreover, knockout of the FUT2 gene restrained fucosylation and the protective effect of l-fucose on barrier function. The severity of colitis was not improved by l-fucose in Fut2 knockout mice. Therefore we conclude that exogenous l-fucose protects intestinal barrier function and relieves intestinal inflammation via upregulation of FUT2-mediated fucosylation of intestinal epithelial cells.