RESUMEN
BACKGROUND AND AIMS: Acute pancreatitis (AP) is a severe pancreatic disorder that remains associated with high mortality due to a lack of effective drugs and management strategies. This study aimed to investigate the molecular pathogenic mechanisms of AP involving p53 and endoplasmic reticulum (ER) stress pathways. METHODS: Expression of PRSS1 and p53 in human AP tissues was detected by immunohistochemistry and Western blotting. AP was induced with caerulein in humanized PRSS1 transgenic mice, and its severity was verified by histological imaging, evaluation of edema, serum amylase, and trypsin activity assays. A transferase-mediated d-UTP nick end-labeling assay was performed to evaluate acinar cell apoptosis associated with AP. The expression of ER stress genes was assessed by quantitative RT-PCR (qRT-PCR) and Western blotting. RESULTS: PRSS1 and p53 were highly expressed in human AP tissues. Expression of human PRSS1 in caerulein-treated mice induced significant acinar cell apoptosis and AP progression. P53 knockout significantly suppressed AP progression in humanized PRSS1 transgenic mice. The ER stress pathway was activated by PRSS1 and mediated the progression of AP in mouse pancreatic tissues. Application of a p53 inhibitor effectively ameliorated caerulein-induced AP in PRSS1 transgenic mice, while a p53 activator promoted the progression of AP. CONCLUSION: P53, which was activated by the ER stress pathway, promoted the progression of AP in mice expressing PRSS1 by inducing acinar cell apoptosis.
Asunto(s)
Células Acinares/metabolismo , Apoptosis/efectos de los fármacos , Estrés del Retículo Endoplásmico/efectos de los fármacos , Pancreatitis/metabolismo , Tripsina/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Animales , Ceruletida , Humanos , Ratones , Ratones TransgénicosRESUMEN
OBJECTIVE: To summarize data from a serological survey of high-risk populations in Guangdong Province, China, and to perform a meta-analysis to investigate the prevalence and seroprevalence of celiac disease (CD) in the Chinese general and high-risk populations. METHODS: We collected data from the serological survey of high-risk population of CD in Guangdong Province, China (N = 1390) by testing their serum tissue transglutaminase immunoglobulin A (tTG-IgA), deamidated gliadin peptides immunoglobulin A (DGP-IgA) and deamidated gliadin peptides immunoglobulin G (DGP-IgG). Additionally, a literature search was performed on PubMed, EMBASE, Cochrane Library and three Chinese databases for articles published up to 20 December 2020 to estimate the pooled prevalence and seroprevalence of CD in China. RESULTS: In the serological survey, 0.94% (13/1390) of individuals were positive for CD antibodies. In a meta-analysis of 18 studies, the seroprevalence of CD in the general Chinese population was 0.27% (95% confidence interval [CI] 0.02%-0.71%). While that in the high-risk population was 8.34% (95% CI 4.90%-12.54%) (odds ratio 7.27, 95% CI 4.06-13.04). The prevalence of biopsy-confirmed CD in high-risk Chinese populations was 4.44% (95% CI 1.53%-8.58%). The seroprevalence of CD varied with patients' geographical origin, being higher in northern China than in southern China. CONCLUSIONS: Early diagnosis of CD by serological screening in high-risk population and generous serological testing in those with vague symptoms, especially in northern China, are recommended.
Asunto(s)
Enfermedad Celíaca , Autoanticuerpos , Enfermedad Celíaca/diagnóstico , Enfermedad Celíaca/epidemiología , China/epidemiología , Gliadina , Humanos , Inmunoglobulina A , Prevalencia , Sensibilidad y Especificidad , Estudios Seroepidemiológicos , TransglutaminasasRESUMEN
BACKGROUND/AIMS: Previous study has shown a positive relationship between the hepatitis B virus (HBV) or hepatitis C virus (HCV) infection and cholangiocarcinoma (CCA); however, their correlation with different anatomical sites of CCA (i.e. ICC and ECC) has not been revealed. This study aims to evaluate the association of HBV or HCV infection with CCA, including the intrahepatic cholangiocarcinoma (ICC) and extrahepatic cholangiocarcinoma (ECC), and to determine the roles of α-1 fetoprotein (AFP), CA19-9, and lymph node involvement in CCA with HBV infection. MATERIALS AND METHODS: Relevant studies published between 2004 and 2016 were systematically searched and retrieved from PubMed, SpringerLink, and Science Direct using key terms such as "cholangiocarcinoma", "bile duct cancer", "extrahepatic cholangiocarcinoma", and "intrahepatic cholangiocarcinoma". The demographic, clinical, and laboratory data were extracted from the included studies, and the meta-analysis was performed using RevMan and STATA 11.0 software. RESULTS: A total of 13 studies with CCA matched the inclusion criteria in this meta-analysis, including 7,113 CCA patients and 24,763 controls. This meta-analysis showed that the HBV or HCV infections can significantly increase the risk of CCA, including ICC and ECC. In addition, the higher levels of AFP, lower levels of CA19-9, and lymph node involvement were detected in the CCA patients with HBV infection as compared to those without. CONCLUSION: The HBV and HCV infections significantly increased the risk of CCA, as well as ICC and ECC. The involvement of AFP, CA19-9, and lymph nodes may play an important role in the diagnosis of CCA.