Helicobacter pylori is a risk factor for the development of peptic ulcers with autophagy dysfunction.Omeprazole was widely known as the first-line regimen for H.pylori-associated gastritis.Objectives:The objective of ...Helicobacter pylori is a risk factor for the development of peptic ulcers with autophagy dysfunction.Omeprazole was widely known as the first-line regimen for H.pylori-associated gastritis.Objectives:The objective of this work was to assess the role of omeprazole on cell pyroptosis and autophagy.Methods:The clinical samples were collected.Quantitative polymerase chain reaction,western blotting,enzyme linked immunosorbent assay,and immunofluorescence(IF)analysis were conducted to reveal the mechanism of omeprazole on cell pyroptosis and autophagy.Results:The results revealed that omeprazole could decrease cell pyroptosis,which was attributed to the downregulation of cleaved caspase-1 expression,resulting in the inhibition of gasdermin E and interleukin-18/1βmaturation and secretion as well as the resolution of inflammation.Mechanistically,omeprazole treatment led to drastic downregulation of mammalian target of rapamycin(mTOR)activity was observed in BGC823 cells,leading to enhanced autophagy characterized by increased LC3II expression,which further reduced cell pyroptosis.This omeprazole-mediated phenomenon was enhanced after phosphodiesterase-4(PDE4)inhibitor dipyridamole(DIP)treatment.In addition,activation of mTOR by MHY1485 could rescue the suppression of cell pyroptosis induced by omeprazole.Most importantly,IF analysis suggested that phosphorylation of mTOR and PDE4 activity and caspase-1 were enhanced in H.pylori-infected gastric mucosa.Conclusion:These findings indicate that omeprazole suppresses cell pyroptosis through PDE4-mediated autophagy in gastric epithelial cells,and DIP enhanced the omeprazole-mediated inhibition of cell pyroptosis,implying that DIP is an alternative combined therapy strategy in improving the treatment of patients with H.pylori infection.展开更多
Rotavirus diarrhea is a major worldwide cause of infantile gastroenteritis; however, the mechanism responsible for intestinal fluid loss remains unclear. Water transfer across the intestinal epithelial membrane seems ...Rotavirus diarrhea is a major worldwide cause of infantile gastroenteritis; however, the mechanism responsible for intestinal fluid loss remains unclear. Water transfer across the intestinal epithelial membrane seems to occur because of aquaporins(AQPs). Accumulating evidence indicates that alterations in AQPs may play an important role in pathogenesis. Here, we focus on changes in AQPs in a mouse model of rotavirus diarrhea. In the present study, 32 of 35 mice developed diarrhea and mild dehydration within 24 hours after infection with rotavirus strain SA11. Intestinal epithelial cells demonstrated cytoplasmic vacuolation, malaligned villi, and atrophy. AQP1 expression was significantly attenuated in the ileum and colon in comparison with controls; likewise, AQP4 and-8 protein expression were significantly decreased in the colon of rotavirus diarrhea-infected mice. In contrast, AQP3 protein expression was significantly increased in the colon of rotavirus-infected mice in comparison with controls. These results indicate that rotavirus diarrhea is associated with the downregulation of AQP1,-4, and-8 expression. Therefore, AQPs play an important role in rotavirus diarrhea.展开更多
Professor Yongsui Dong(April 1932–January 2023)was a chief physician and doctoral supervisor of the Department of Pediatrics,Tongji Hospital,Tongji Medical College of Huazhong University of Science and Technology,and...Professor Yongsui Dong(April 1932–January 2023)was a chief physician and doctoral supervisor of the Department of Pediatrics,Tongji Hospital,Tongji Medical College of Huazhong University of Science and Technology,and a pioneer,medical educator,and clinical scientist in the field of pediatric infectious and digestive diseases in China.Professor Dong graduated from the Medical College of Fudan University(formerly Shanghai First Medical College)with excellent grades in 1956.展开更多
In response to the current coronavirus disease 2019(COVID-19)pandemic,it is crucial to understand the origin,transmission,and evolution of severe acute respiratory syndrome coronavirus 2(SARS-Co V-2),which relies on c...In response to the current coronavirus disease 2019(COVID-19)pandemic,it is crucial to understand the origin,transmission,and evolution of severe acute respiratory syndrome coronavirus 2(SARS-Co V-2),which relies on close surveillance of genomic diversity in clinical samples.Although the mutation at the population level had been extensively investigated,how the mutations evolve at the individual level is largely unknown.Eighteen time-series fecal samples were collected from nine patients with COVID-19 during the convalescent phase.The nucleic acids of SARS-CoV-2 were enriched by the hybrid capture method.First,we demonstrated the outstanding performance of the hybrid capture method in detecting intra-host variants.We identified 229 intra-host variants at 182 sites in 18 fecal samples.Among them,nineteen variants presented frequency changes>0.3 within 1-5 days,reflecting highly dynamic intrahost viral populations.Moreover,the evolution of the viral genome demonstrated that the virus was probably viable in the gastrointestinal tract during the convalescent period.Meanwhile,we also found that the same mutation showed a distinct pattern of frequency changes in different individuals,indicating a strong random drift.In summary,dramatic changes of the SARS-CoV-2 genome were detected in fecal samples during the convalescent period;whether the viral load in feces is sufficient to establish an infection warranted further investigation.展开更多
基金supported by National Natural Science Foundation of China(No.82200607)Guangdong Basic and Applied Basic Research Foundation(Nos.2020A1515110109,2021A1515012194,2023A1515030064)+3 种基金Basic and Applied Research Project of Guangzhou Municipal Science and Technology Project(No.202201020631)Guangzhou Medical Key Disciplines and Specialties(No.011006003)Guangzhou Key Laboratory of Pediatric Inflammatory Bowel Disease(No.2023A03J0866)National Health Commission Key Laboratory of Tropical Disease Prevention and Control(2022NHCTDCKFKT21001).
文摘Helicobacter pylori is a risk factor for the development of peptic ulcers with autophagy dysfunction.Omeprazole was widely known as the first-line regimen for H.pylori-associated gastritis.Objectives:The objective of this work was to assess the role of omeprazole on cell pyroptosis and autophagy.Methods:The clinical samples were collected.Quantitative polymerase chain reaction,western blotting,enzyme linked immunosorbent assay,and immunofluorescence(IF)analysis were conducted to reveal the mechanism of omeprazole on cell pyroptosis and autophagy.Results:The results revealed that omeprazole could decrease cell pyroptosis,which was attributed to the downregulation of cleaved caspase-1 expression,resulting in the inhibition of gasdermin E and interleukin-18/1βmaturation and secretion as well as the resolution of inflammation.Mechanistically,omeprazole treatment led to drastic downregulation of mammalian target of rapamycin(mTOR)activity was observed in BGC823 cells,leading to enhanced autophagy characterized by increased LC3II expression,which further reduced cell pyroptosis.This omeprazole-mediated phenomenon was enhanced after phosphodiesterase-4(PDE4)inhibitor dipyridamole(DIP)treatment.In addition,activation of mTOR by MHY1485 could rescue the suppression of cell pyroptosis induced by omeprazole.Most importantly,IF analysis suggested that phosphorylation of mTOR and PDE4 activity and caspase-1 were enhanced in H.pylori-infected gastric mucosa.Conclusion:These findings indicate that omeprazole suppresses cell pyroptosis through PDE4-mediated autophagy in gastric epithelial cells,and DIP enhanced the omeprazole-mediated inhibition of cell pyroptosis,implying that DIP is an alternative combined therapy strategy in improving the treatment of patients with H.pylori infection.
基金supported by funding from Guangdong Natural Science Foundation (grants:S2012010009211,S2012010009538)Key Specialty Projects of Guangzhou Board of Health (grant:20121A021014)
文摘Rotavirus diarrhea is a major worldwide cause of infantile gastroenteritis; however, the mechanism responsible for intestinal fluid loss remains unclear. Water transfer across the intestinal epithelial membrane seems to occur because of aquaporins(AQPs). Accumulating evidence indicates that alterations in AQPs may play an important role in pathogenesis. Here, we focus on changes in AQPs in a mouse model of rotavirus diarrhea. In the present study, 32 of 35 mice developed diarrhea and mild dehydration within 24 hours after infection with rotavirus strain SA11. Intestinal epithelial cells demonstrated cytoplasmic vacuolation, malaligned villi, and atrophy. AQP1 expression was significantly attenuated in the ileum and colon in comparison with controls; likewise, AQP4 and-8 protein expression were significantly decreased in the colon of rotavirus diarrhea-infected mice. In contrast, AQP3 protein expression was significantly increased in the colon of rotavirus-infected mice in comparison with controls. These results indicate that rotavirus diarrhea is associated with the downregulation of AQP1,-4, and-8 expression. Therefore, AQPs play an important role in rotavirus diarrhea.
文摘Professor Yongsui Dong(April 1932–January 2023)was a chief physician and doctoral supervisor of the Department of Pediatrics,Tongji Hospital,Tongji Medical College of Huazhong University of Science and Technology,and a pioneer,medical educator,and clinical scientist in the field of pediatric infectious and digestive diseases in China.Professor Dong graduated from the Medical College of Fudan University(formerly Shanghai First Medical College)with excellent grades in 1956.
基金supported by grants from National Key R&D Program of China(2020YFC0848900)the Strategic Priority CAS Project(XDB38000000)Chinese Academy of Sciences and the National Major Science and Technology Project for Control and Prevention of Major Infectious Diseases in China(2018ZX10305409,2018ZX10301401,2018ZX10732401)
文摘In response to the current coronavirus disease 2019(COVID-19)pandemic,it is crucial to understand the origin,transmission,and evolution of severe acute respiratory syndrome coronavirus 2(SARS-Co V-2),which relies on close surveillance of genomic diversity in clinical samples.Although the mutation at the population level had been extensively investigated,how the mutations evolve at the individual level is largely unknown.Eighteen time-series fecal samples were collected from nine patients with COVID-19 during the convalescent phase.The nucleic acids of SARS-CoV-2 were enriched by the hybrid capture method.First,we demonstrated the outstanding performance of the hybrid capture method in detecting intra-host variants.We identified 229 intra-host variants at 182 sites in 18 fecal samples.Among them,nineteen variants presented frequency changes>0.3 within 1-5 days,reflecting highly dynamic intrahost viral populations.Moreover,the evolution of the viral genome demonstrated that the virus was probably viable in the gastrointestinal tract during the convalescent period.Meanwhile,we also found that the same mutation showed a distinct pattern of frequency changes in different individuals,indicating a strong random drift.In summary,dramatic changes of the SARS-CoV-2 genome were detected in fecal samples during the convalescent period;whether the viral load in feces is sufficient to establish an infection warranted further investigation.