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BACKGROUND AND AIMS: Adequate bowel preparation is crucial for clear mucosal visualization during colonoscopy. We aimed to comprehensively compare oral sulfate solution (OSS) and 3-L split-dose polyethylene glycol (PEG) for bowel preparation before colonoscopy. METHODS: This randomized, active-controlled, noninferiority study was performed in 10 medical centers. Eligible subjects were enrolled to receive OSS or 3-L PEG in a split-dose regimen. The quality of bowel preparation, adverse reactions, and acceptability were evaluated. The quality of bowel preparation was evaluated using the Boston Bowel Preparation Scale. Safety was evaluated by adverse reactions. The study population was divided into the full analysis set (FAS), the safety set, the modified FAS (mFAS), and the per-protocol set (PPS). RESULTS: Three hundred forty-eight potentially eligible subjects were enrolled. Three hundred forty-four subjects were included in the FAS and safety set, 340 subjects were included in the mFAS, and 328 subjects were included in the PPS. Adequate bowel preparation of the OSS was not inferior to 3-L PEG in the mFAS (98.22% vs 97.66%) and the PPS (98.17% vs 98.78%). There was no significant difference in acceptability between the 2 groups (94.74% vs 94.80%, P = .9798). Overall adverse reactions were similar (50.88% vs 44.51%, P = .2370) between the 2 groups. CONCLUSIONS: The split-dose OSS regimen was not inferior to the split-dose 3-L PEG regimen for the quality of bowel preparation in a Chinese adult population. The safety and acceptability of the 2 groups were similar. (Clinical trial registration number: NCT05465889.).
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Catárticos , Polietilenoglicóis , Adulto , Humanos , Polietilenoglicóis/efeitos adversos , Sulfatos , Colonoscopia/métodos , Administração OralRESUMO
BACKGROUND & AIMS: We performed a systematic review and meta-analysis to comprehensively estimate adenoma miss rate (AMR) and advanced AMR (AAMR) and explore associated factors. METHODS: We searched the PubMed, Web of Science, and Ovid EMBASE databases for studies published through April 2018 on tandem colonoscopies, with AMR and AAMR as the primary outcomes. We performed meta-regression analyses to identify risk factors and factors associated with outcome. Primary outcomes were AMR and AAMR and secondary outcomes were AMR and AAMR for different locations, sizes, pathologies, morphologies, and populations. RESULTS: In a meta-analysis of 43 publications and more than 15,000 tandem colonoscopies, we calculated miss rates of 26% for adenomas (95% confidence interval [CI] 23%-30%), 9% for advanced adenomas (95% CI 4%-16%), and 27% for serrated polyps (95% CI 16%-40%). Miss rates were high for proximal advanced adenomas (14%; 95% CI 5%-26%), serrated polyps (27%; 95% CI 16%-40%), flat adenomas (34%; 95% CI 24%-45%), and in patients at high risk for colorectal cancer (33%; 95% CI 26%-41%). Miss rates could be decreased by adequate bowel preparation and auxiliary techniques (P = .06; P = .04, and P = .01, respectively). The adenoma detection rate (ADR), adenomas per index colonoscopy, and adenomas per positive index colonoscopy (APPC) were independently associated with AMR (P = .02, P = .01, and P = .008, respectively), whereas APPC was the only factor independently associated with AAMR (P = .006). An APPC value greater than 1.8 was more effective in monitoring AMR (31% vs 15% for AMR P < .0001) than an ADR value of at least 34% (27% vs 17% for AMR; P = .008). The AAMR of colonoscopies with an APPC value below 1.7 was 35%, vs 2% for colonoscopies with an APPC value of at least 1.7 (P = .0005). CONCLUSIONS: In a systematic review and meta-analysis, we found that adenomas and advanced adenomas are missed (based on AMR and AAMR) more frequently than previously believed. In addition to ADR, APPC deserves consideration as a complementary indicator of colonoscopy quality, if it is validated in additional studies.
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Adenoma/diagnóstico por imagem , Pólipos do Colo/diagnóstico por imagem , Colonoscopia , Neoplasias Colorretais/diagnóstico por imagem , Erros de Diagnóstico/estatística & dados numéricos , Adenoma/patologia , Colo/patologia , Pólipos do Colo/patologia , Neoplasias Colorretais/patologia , Humanos , Fatores de Risco , Carga TumoralRESUMO
Aims: The studies on post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) in pancreas divisum (PD) patients without chronic pancreatitis (CP) are rare. In this study, we aimed to evaluate the incidence of PEP in PD patients without CP and the risk and protective factors for PEP.Methods: Consecutive patients with symptomatic PD that underwent ERCP from January 2005 to December 2017 were retrospectively analyzed. The patients were divided into PD without CP group and CP group. The basic information and medical records of patients were collected. The risk and protective factors for PEP in PD patients without CP were analyzed by univariate logistic analysis.Results: A total of 89 ERCP procedures were performed in 51 PD patients without CP, and 249 procedures in 136 patients with CP. The incidence of PEP was significantly higher in PD patients without CP than those with CP (15.7% vs. 5.6%, p = .005). Female gender were independent risk factors for PEP, while dorsal duct stent placement was a protective factor.Conclusion: CP may be a protective factor against PEP in PD patients. Female was a risk factor for PEP in PD patients and dorsal duct stent placement was a preventive factor that reduced the incidence of PEP in PD patients without CP.
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Colangiopancreatografia Retrógrada Endoscópica , Pâncreas/anormalidades , Pancreatite Crônica/etiologia , Medição de Risco/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , China/epidemiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Pâncreas/diagnóstico por imagem , Pancreatite Crônica/epidemiologia , Fatores de Proteção , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Adulto JovemRESUMO
The intestinal tract consists of various types of cells, such as epithelial cells, Paneth cells, macrophages, and lymphocytes, which constitute the intestinal immune system and play a significant role in maintaining intestinal homeostasis by producing antimicrobial materials and controlling the host-commensal balance. Various studies have found that the dysfunction of intestinal homeostasis contributes to the pathogenesis of inflammatory bowel disease (IBD). As a novel mediator, extracellular vesicles (EVs) have been recognized as effective communicators, not only between cells but also between cells and the organism. In recent years, EVs have been regarded as vital characters for dysregulated homeostasis and IBD in either the etiology or the pathology of intestinal inflammation. Here, we review recent studies on EVs associated with intestinal homeostasis and IBD and discuss their source, cargo, and origin, as well as their therapeutic effects on IBD, which mainly include artificial nanoparticles and EVs derived from microorganisms.
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Vesículas Extracelulares/metabolismo , Homeostase , Doenças Inflamatórias Intestinais/patologia , Intestinos/patologia , Animais , Biomarcadores/metabolismo , Colite , Progressão da Doença , Enterócitos , Microbioma Gastrointestinal , Humanos , Sistema Imunitário , Inflamação , Doenças Inflamatórias Intestinais/imunologia , Mucosa Intestinal/imunologia , Camundongos , Microbiota , Modelos Biológicos , Nanopartículas/química , Nanotecnologia/métodos , Celulas de PanethAssuntos
Ductos Pancreáticos , Pancreatite , Recidiva , Humanos , Ductos Pancreáticos/diagnóstico por imagem , Pancreatite/etiologia , Pancreatite/complicações , Doença Aguda , Masculino , Colangiopancreatografia Retrógrada Endoscópica , Coristoma/complicações , Coristoma/diagnóstico por imagem , Coristoma/cirurgia , Feminino , Pessoa de Meia-IdadeRESUMO
BACKGROUND AND AIMS: Colonoscopy insertion is painful for some patients and is one of the main barriers to screening colonoscopy. Few studies have assessed the impact of the supine position (SP) on colonoscopy insertion, especially for unsedated patients. The aim of this randomized controlled trial was to clarify this issue. METHODS: Unsedated patients were randomized to SP or left horizontal position (LHP) as the starting position of colonoscopy insertion. The primary outcome measure was cecal intubation time (CIT), and the secondary outcome measures were descending colon intubation time (DIT), pain score of patients, difficulty score according to the endoscopist, and patients' acceptance of unsedated colonoscopy. RESULTS: A total of 347 patients were randomized to the SP group (175) or the LHP group (172). The CIT in the SP group was significantly shorter than that in the LHP group (275.0 seconds [interquartile range (IQR), 234.0-328.5 seconds] versus 316.0 seconds [IQR, 261.0-370.0 seconds], P < .001). The DIT was also shorter in the SP group (64.5 seconds [IQR, 52.0-86.3 seconds] versus 74.0 seconds [IQR, 62.0-92.0 seconds], P = .001). Compared with the LHP, the SP had a lower pain score (3.3 versus 3.9, P = .002), a lower difficulty score (3.1 versus 3.7, P < .001), a lower frequency of position change (7.1% versus 38.0%, P < .001), and less need for abdominal compression (39.1% versus 45.5%, P = .02). SP was the only modifiable and independent factor identified to reduce CIT and pain score and improve patients' acceptance of unsedated colonoscopy. CONCLUSIONS: As an economical and convenient method, SP can reduce CIT, ease pain, and improve patients' acceptance of unsedated colonoscopy. (Clinical trial registration number: NCT03289442.).
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Colonoscopia/métodos , Neoplasias Colorretais/diagnóstico , Duração da Cirurgia , Dor Processual/fisiopatologia , Aceitação pelo Paciente de Cuidados de Saúde , Posicionamento do Paciente/métodos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Decúbito DorsalRESUMO
BACKGROUND AND AIMS: Colonoscopy insertion is technically challenging, time-consuming, and painful, especially for the sigmoid. Several pilot studies indicated that the (left) tilt-down position could facilitate the insertion procedure, but no formal trials have been published to demonstrate its efficacy. We performed this study to verify the benefits of the left lateral tilt-down position (LTDP) on the insertion process. METHODS: This 2-center prospective trial randomized unsedated patients to the LTDP or left lateral horizontal position (LHP) to aid insertion. The primary outcome measure was cecal intubation time (CIT). Secondary outcome measures included decending colon intubation time (DIT), pain score of insertion, acceptance of unsedated colonoscopy for future examinations, difficulty score for insertion, and the adverse event rate of colonoscopy. RESULTS: Two hundred fifty-eight patients were randomized to the LTDP (128) or LHP (130) in 2 centers. The median CIT and DIT were shorter with patients positioned in LTDP than in LHP (CIT, 280.0 vs 339.5 s, P < .001; DIT, 53.0 vs 69.0 s, P < .001, respectively) and patients with high and low body mass index (BMI) benefited more from LTDP than from LHP, as opposed to patients with normal BMI. In addition, colonoscopy insertion in LTDP was less painful (3.4 ± 1.6 vs 4.0 ± 1.7, P = .02) and less difficult (3.1 ± 1.9 vs 3.7 ± 1.4, P < .001), showing a higher tendency to acceptance of unsedated colonoscopy (82.9% vs 73.8%, P = .08). The rates of adverse events were extremely low and did not differ significantly in the 2 groups. CONCLUSIONS: LTDP for colonoscopy insertion can reduce insertion time and pain, and potentially improves patients' acceptance of unsedated colonoscopy. (Clinical trial registration number: NCT02842489.).
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Colonoscopia/métodos , Posicionamento do Paciente/métodos , Adolescente , Adulto , Idoso , Colo/cirurgia , Colonoscopia/efeitos adversos , Feminino , Humanos , Intubação/efeitos adversos , Intubação/métodos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Dor/etiologia , Medição da Dor , Posicionamento do Paciente/efeitos adversos , Estudos Prospectivos , Fatores de Tempo , Adulto JovemRESUMO
BACKGROUND AND AIM: Endoscopic retrograde cholangiopancreatography (ERCP) is associated with risk of complications. Methods to facilitate ductal cannulation may reduce complications. Intraduodenal acid infusion is a physiological approach to stimulate secretin release in human body and may facilitate cannulation. The objective of this study was to investigate the effect of intraduodenal acid infusion on pancreatic duct cannulation during ERCP. METHODS: It was a single center, double-blind, randomized controlled trial. Consecutive patients undergoing first ERCP for pancreatic diseases were randomized toreceive 50 mL acetic acid intraduodenal infusion at ERCP (acetic acid group) or 50 mL saline (control group). The primary outcome, difficult cannulation rate (cannulation time >5 min), in the two groups was compared. RESULTS: Two hundred ten patients were included in the final analysis (105 in each group). The difficult cannulation rate were 39.1% in the control group and 20.9% in the acetic acid group, and the difference was statistically significant (P = 0.004). The overall successful deep cannulation rate was 89.5% and 85.7%, respectively (P = 0.402). The cannulation time was remarkably shortened (182 vs 286 s, P = 0.018), and the cannulation attempts were significantly decreased (3.4 vs 4.4, P = 0.008). The fluoroscopy time was also significantly reduced (60 vs 86 s, P = 0.028). The incidence of post-ERCP pancreatitis and hyperamylasemia was comparable (7.6% vs 10.5% and 10.5% vs 19.1%, P > 0.05). CONCLUSION: Intraduodenal acetic acid infusion can significantly decrease difficult pancreatic cannulation rate, facilitate pancreatic duct cannulation, and reduce radiation exposure (ClinicalTrials.gov number, NCT02800772).
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Ácido Acético/administração & dosagem , Cateterismo/efeitos adversos , Cateterismo/métodos , Colangiopancreatografia Retrógrada Endoscópica/efeitos adversos , Colangiopancreatografia Retrógrada Endoscópica/métodos , Pancreatopatias/diagnóstico , Ductos Pancreáticos , Adolescente , Adulto , Método Duplo-Cego , Feminino , Fluoroscopia/efeitos adversos , Humanos , Hiperamilassemia/etiologia , Hiperamilassemia/prevenção & controle , Infusões Intralesionais , Masculino , Pessoa de Meia-Idade , Pancreatite/etiologia , Pancreatite/prevenção & controle , Adulto JovemRESUMO
Background: Lifestyle modification is the cornerstone of non-alcoholic fatty liver disease (NAFLD) prevention and treatment. Short video platforms can facilitate easier access to health information for patients, thereby influencing lifestyle changes. An increasing number of individuals rely on online platforms to acquire health-related information about NAFLD. However, the quality of information regarding NAFLD on these platforms remains unclear. Objective: This study aimed to investigate the quality of information about NAFLD on TikTok. Methods: A total of 497 videos were retrieved from TikTok. The basic video information, including the video source, was extracted. Two independent raters evaluated the quality and reliability of the videos using the Global Quality Score system and a modified DISCERN tool. Propensity score matching (PSM) was used to compare video quality across sources. Results: NAFLD-related videos on TikTok were divided into three groups according to the uploader: health professionals, medical institutions, and science bloggers. Overall, the quality of NAFLD videos on TikTok was not satisfactory. Before PSM, there were no significant differences in video quality or content between the three groups. After PSM, the quality of NAFLD videos from health professionals was significantly better than the videos created by other groups. Besides, the videos of health professionals outperformed those of medical institutions and science bloggers in terms of the definition of disease, risk factors, and treatment, but were inferior to those of medical institutions considering the symptoms and tests of NAFLD. Conclusion: The quality of NAFLD-related videos on TikTok needs improvement. Compared with videos created by science bloggers and medical institutions, videos from health professionals may provide accurate guidance on the treatment and prevention of NAFLD.
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Hepatopatia Gordurosa não Alcoólica , Mídias Sociais , Humanos , Pontuação de Propensão , Reprodutibilidade dos Testes , Fatores de RiscoRESUMO
BACKGROUND & AIM: Exosomes are effective mediators of cell-to-cell interactions and transport several regulatory molecules, including microRNAs (miRNAs), involved in diverse fundamental biological processes. The role of macrophage-derived exosomes in the development of inflammatory bowel disease (IBD) has not been previously reported. This study investigated specific miRNAs in macrophage-derived exosomes in IBD and their molecular mechanism. METHODS: A dextran sulfate sodium (DSS)-induced IBD mouse model was established. The culture supernatant of murine bone marrow-derived macrophages (BMDMs) cultured with or without lipopolysaccharide (LPS) was used for isolating exosomes, which were subjected to miRNA sequencing. Lentiviruses were used to alter miRNA expression and investigate the role of macrophage-derived exosomal miRNAs. Both mouse and human organoids were co-cultured with macrophages in a Transwell system to model cellular IBD in vitro. RESULTS: LPS-induced macrophages released exosomes containing various miRNAs and exacerbated IBD. Based on miRNA sequencing of macrophage-derived exosomes, miR-223 was selected for further analysis. Exosomes with upregulated miR-223 expression contributed to the exacerbation of intestinal barrier dysfunction in vivo, which was further verified using both mouse and human colon organoids. Furthermore, time-dependent analysis of the mRNAs in DSS-induced colitis mouse tissue and miR-223 target gene prediction were performed to select the candidate gene, resulting in the identification of the barrier-related factor Tmigd1. CONCLUSION: Macrophage-derived exosomal miR-223 has a novel role in the progression of DSS-induced colitis by inducing intestinal barrier dysfunction through the inhibition of TMIGD1.
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Colite , Exossomos , Doenças Inflamatórias Intestinais , MicroRNAs , Humanos , Camundongos , Animais , Exossomos/metabolismo , Lipopolissacarídeos/farmacologia , Doenças Inflamatórias Intestinais/metabolismo , MicroRNAs/genética , Colite/induzido quimicamente , Macrófagos/metabolismo , Glicoproteínas de Membrana/metabolismoRESUMO
Background and aims: Compared with self-prepared LRD, a prepackaged low-residue diet (LRD) can improve patient compliance, but whether it can further improve the quality of bowel preparation is uncertain. The study aimed to compare the application of the prepackaged formula LRD with self-prepared LRD in bowel preparation for colonoscopy. Methods: A multicenter randomized controlled trial was conducted in 15 centers. The eligible subjects were randomly assigned to one of two groups: the formula LRD group and the self-prepared LRD group. On the day before the colonoscopy, subjects in the self-prepared LRD group were instructed to consume a restricted LRD prepared by themselves, while subjects in the formula LRD group were given six bags of prepackaged formula LRD and instructed to consume them according to their individual need. The primary outcome was an adequate bowel preparation rate. Secondary outcomes mainly included Boston Bowel Preparation Scale (BBPS) scores, dietary restriction compliance rate, tolerance, satisfaction, adenoma detection rate (ADR), and adverse reactions. The trial was registered at ClinicalTrials.gov under the identifier NCT03943758. Results: A total of 550 subjects were recruited. Compared with the self-prepared LRD group, the formula LRD group showed a higher adequate bowel preparation rate (94.5 vs. 80.4%; P < 0.01), BBPS scores (7.87 ± 1.13 vs. 6.75 ± 1.47; P < 0.01), dietary compliance rate (92.4 vs. 78.9%; P < 0.01), tolerance (P < 0.01 in degree of hunger, intensity of physical strength, and negative influence on daily activities), satisfaction (8.56 ± 1.61 vs. 7.20 ± 2.02; P < 0.01), and ADR (25.6 vs. 16.0%; P < 0.01). There was no significant difference in adverse reactions. Conclusion: Compared with self-prepared LRD, the formula LRD showed similar safety and higher bowel preparation quality, compliance, and tolerance in bowel preparation. More formula LRDs could be designed according to different dietary habits and ethnic populations, and further researches are warranted to confirm their effect. Clinical trial registration: https://register.clinicaltrials.gov, identifier: NCT03943758.
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No fully validated risk-stratification strategies have been established in China where colonoscopies resources are limited. We aimed to develop and validate a fecal immunochemical test (FIT)-based risk-stratification model for colorectal neoplasia (CN); 10,164 individuals were recruited from 175 centers nationwide and were randomly allocated to the derivation (n = 6776) or validation cohort (n = 3388). Multivariate logistic analyses were performed to develop the National Colorectal Polyp Care (NCPC) score, which formed the risk-stratification model along with FIT. The NCPC score was developed from eight independent predicting factors and divided into three levels: low risk (LR 0-14), intermediate risk (IR 15-17), and high risk (HR 18-28). Individuals with IR or HR of NCPC score or FIT+ were classified as increased-risk individuals in the risk-stratification model and were recommended for colonoscopy. The IR/HR of NCPC score showed a higher prevalence of CNs (21.8%/32.8% vs. 11.0%, P < 0.001) and ACNs (4.3%/9.2% vs. 2.0%, P < 0.001) than LR, which was also confirmed in the validation cohort. Similar relative risks and predictive performances were demonstrated between non-specific gastrointestinal symptoms (NSGS) and asymptomatic cohort. The risk-stratification model identified 73.5% CN, 82.6% ACN, and 93.6% CRC when guiding 52.7% individuals to receive colonoscopy and identified 55.8% early-onset ACNs and 72.7% early-onset CRCs with only 25.6% young individuals receiving colonoscopy. The risk-stratification model showed a good risk-stratification ability for CN and early-onset CRCs in Chinese population, including individuals with NSGS and young age.
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Neoplasias Colorretais , Detecção Precoce de Câncer , Humanos , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologia , Estudos Prospectivos , Fatores de RiscoRESUMO
BACKGROUND: Colon cancer is one of the most frequent malignancies and causes high mortality worldwide. Exploring the tumor-immune interactions in the tumor microenvironment and identifying new prognostic and therapeutic biomarkers will assist in decoding the novel mechanism of tumor immunotherapy. BGN is a typical extracellular matrix protein that was previously validated as a signaling molecule regulating multiple processes of tumorigenesis. However, its role in tumor immunity requires further investigation. METHODS: The differentially expressed genes in three GEO datasets were analyzed, and BGN was identified as the target gene by intersection analysis of PPIs. The relevance between clinical outcomes and BGN expression levels was evaluated using data from the GEO database, TCGA and tissue microarray of colon cancer samples. Univariable and multivariable Cox regression models were conducted for identifying the risk factors correlated with clinical prognosis of colon cancer patients. Next, the association between BGN expression levels and the infiltration of immune cells as well as the process of the immune response was analyzed. Finally, we predicted the immunotherapeutic response rates in the subgroups of low and high BGN expression by TIS score, ImmuCellAI and TIDE algorithms. RESULTS: BGN expression demonstrated a statistically significant upregulation in colon cancer tissues than in normal tissues. Elevated BGN was associated with shorter overall survival as well as unfavorable clinicopathological features, including tumor size, serosa invasion and length of hospitalization. Mechanistically, pathway enrichment and functional analysis demonstrated that BGN was positively correlated with immune and stromal scores in the TME and primarily involved in the regulation of immune response. Further investigation revealed that BGN was strongly expressed in the immunosuppressive phenotype and tightly associated with the infiltration of multiple immune cells in colon cancer, especially M2 macrophages and induced Tregs. Finally, we demonstrated that high BGN expression presented a better immunotherapeutic response in colon cancer patients. CONCLUSION: BGN is an encouraging predictor of diagnosis, prognosis and immunotherapeutic response in patients with colon cancer. Assessment of BGN expression represents a novel approach with great promise for identifying patients who may potentially benefit from immunotherapy.
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Intestinal mucosal barrier, mainly consisting of the mucus layer and epithelium, functions in absorbing nutrition as well as prevention of the invasion of pathogenic microorganisms. Paneth cell, an important component of mucosal barrier, plays a vital role in maintaining the intestinal homeostasis by producing antimicrobial materials and controlling the host-commensal balance. Current evidence shows that the dysfunction of intestinal mucosal barrier, especially Paneth cell, participates in the onset and progression of inflammatory bowel disease (IBD). Autophagy, a cellular stress response, involves various physiological processes, such as secretion of proteins, production of antimicrobial peptides, and degradation of aberrant organelles or proteins. In the recent years, the roles of autophagy in the pathogenesis of IBD have been increasingly studied. Here in this review, we mainly focus on describing the roles of Paneth cell autophagy in IBD as well as several popular autophagy-related genetic variants in Penath cell and the related therapeutic strategies against IBD.
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Autofagia , Doenças Inflamatórias Intestinais/imunologia , Celulas de Paneth/imunologia , Animais , Estresse do Retículo Endoplasmático , Variação Genética , Humanos , Doenças Inflamatórias Intestinais/genética , Espécies Reativas de OxigênioRESUMO
AIMS: Gender-related phenotypes in the cardiovascular system have been observed in various genetically modified mice. Here, we report that cardiac functions are significantly improved only in male CD38-null mice and we explore the potential mechanisms of the sexual dimorphism mediated by CD38 deficiency. MAIN METHODS: Cardiac functions of mice were measured by pressure-volume conductance catheter technique and echocardiography. Serum sex steroids were determined by radioimmunoassay. Relative mRNA levels of myocardial contractile-associated proteins in cardiomyocytes were analyzed by real-time PCR analysis. To clarify the effects of testosterone on the sexual dimorphism, flutamide, an androgen receptor antagonist, was subcutaneously infused into the male null mice for 6 weeks with an osmotic mini-pump. KEY FINDINGS: The myocardial contractility, contraction and relaxation velocities were significantly enhanced only in male CD38-null mice, in which the levels of serum testosterone were markedly elevated. The elevated testosterone levels in the null mice were correlated to an obvious decrease in expression of androgen receptor and dramatic increases in expressions of major genes involved in myocardial contraction, including ryanodine receptor type 2 (RyR2), sarcoplasmic reticular Ca(2+) ATPase (SERCA2) and Na(+)/Ca(2+)-exchanger protein 1 (NCX1), and α myosin heavy chain (α-MHC). More importantly, all of the alternations that were observed in the male null mice were almost completely restored by flutamide administration. SIGNIFICANCE: Elevated serum level of testosterone in the male CD38(-/-) mice enhances cardiac functions through upregulation of major calcium regulatory proteins, which improve our understanding on sex disparities and molecular mechanisms in the incidence and manifestation of heart diseases.