ABSTRACT
BACKGROUND: The effect of human 8-Oxoguanine DNA Glycosylase (hOGG1) on exogenous chemicals in esophageal squamous cell carcinoma (ESCC) remain unclear. The study plans to determine hOGG1 expression levels in ESCC and possible interactions with known environmental risk factors in ESCC. MATERIAL AND METHODS: We analyzed levels of exposure to urinary nitrosamines in volunteers from high and low prevalence areas by GC-MS. And we performed the interaction between hOGG1 gene and nitrosamine disinfection by-products by analyzing hOGG1 gene expression in esophageal tissues. RESULTS: In ESCC, nitrosamine levels were significantly increased and hOGG1 mRNA expression levels were significantly decreased. There was a statistically significant interaction between reduced hOGG1 mRNA levels and non-tap drinking water sources in ESCC. The apparent indirect association between ESCC and NMEA indicated that 33.4% of the association between ESCC and NMEA was mediated by hOGG1. CONCLUSION: In populations which exposed to high levels of environmental pollutants NDMA, low expression of hOGG1 may promote the high incidence of esophageal cancer in Huai'an. hOGG1 may be a novel mediator in nitrosamine-induced esophageal tumorigenesis.
Subject(s)
Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Nitrosamines , Humans , Esophageal Neoplasms/chemically induced , Esophageal Neoplasms/genetics , Esophageal Squamous Cell Carcinoma/chemically induced , Esophageal Squamous Cell Carcinoma/complications , Nitrosamines/toxicity , Cell Transformation, Neoplastic , RNA, MessengerABSTRACT
BACKGROUND: The inflammatory response after hepatic ischemia reperfusion (I/R) contributes to liver dysfunction and failure after transplantation. Butyrate is a four-carbon fatty acid, normally produced by bacterial fermentation of fiber in mammalian intestines, with anti-inflammatory activities. The purpose of the present study was to investigate the protective effect of butyrate preconditioning, if any, against hepatic I/R injury in rats and the underlying mechanisms involved. METHODS: Male Sprague-Dawley rats were subjected to a partial (70%) hepatic ischemia for 60 min after pretreatment with either vehicle or butyrate, followed by 3, 6, and 24 h of reperfusion. Hepatic injury was evaluated by biochemical and histopathologic examinations. Neutrophil infiltration was measured by myeloperoxidase (MPO) activity. The expression of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) was measured by enzyme-linked immunosorbent assay (Elisa) and Real-time reverse-transcriptase polymerase chain reaction (RT-PCR). The expression of nuclear factor kappa B (NF-κB) p65 was determined by immunohistochemistry and Western blot analysis. RESULTS: Butyrate treatment markedly improved hepatic function and histology, as indicated by reduced transaminase levels and ameliorated tissue pathologic changes. The expression of tumor necrosis factor-alpha, interleukin-6, and myeloperoxidase activity was attenuated by butyrate. Butyrate also reduced I/R-induced nuclear translocation of NF-κB p65 in Kupffer cells. CONCLUSION: Our results suggest that butyrate alleviates I/R-induced liver injury, possibly by suppressing inflammatory factors production and preventing NF-κB activation in Kupffer cells.
Subject(s)
Butyrates/pharmacology , Hepatitis/drug therapy , Kupffer Cells/drug effects , Reperfusion Injury/drug therapy , Transcription Factor RelA/antagonists & inhibitors , Transplantation Conditioning/methods , Animals , Cell Nucleus/metabolism , Hepatitis/immunology , Hepatitis/metabolism , Interleukin-6/genetics , Interleukin-6/metabolism , Kupffer Cells/metabolism , Liver/drug effects , Liver/immunology , Liver/metabolism , Liver Transplantation , Male , Neutrophils/immunology , Peroxidase/metabolism , RNA, Messenger/metabolism , Rats , Rats, Sprague-Dawley , Reperfusion Injury/immunology , Reperfusion Injury/metabolism , Transcription Factor RelA/metabolism , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/metabolismABSTRACT
OBJECTIVE: To investigate the impact of polyethylene glycols (PEG) upon islet survival in homogeneous murine islet transplantation and understand the impact of PEGylation in combination with rapamycin upon anti-rejection therapy in homogeneous mice islet transplantation. METHODS: The subcutaneously pre-vascularized STZ-induced diabetic mice treated with transplanted islets of BALB/c mice were randomly divided into 6 groups: Group A with normal mice islets; Group B with PEG-packed islets; Group C with normal mice islets and 1.5 mg x kg(-1) x d(-1) rapamycin; Group D with PEG-packed islets and 1.5 mg x kg(-1) x d(-1) rapamycin; Group E with normal mice islets and 3 mg x kg(-1) x d(-1) rapamycin; Group F with PEG-packed islets and 3 mg x kg(-1) x d(-1) rapamycin. The post-transplantation blood glucose was monitored. Transplanted islets were analyzed by H&E and insulin immunostain. RESULTS: The survival time in group B was significantly prolonged as compared with group A (P < 0.01). The survival time in group C were (35.0 +/- 3.1) d and groups D, E, F had survival of up to 6 weeks. Transplantation sites of group A were observed with a more abundant infiltration of immune cells than group B. And the unmodified islets in group A were completely destroyed after transplantation. Insulin-positive islet cells were not detected at the entire transplantation site in group A while the presence was found at the transplantation site in group B. CONCLUSION: PEG-packed islets can significantly improve the survival time of transplanted islets. When combined with rapamycin, it can reduce the dose of rapamycin.
