BACKGROUND Acute pancreatitis(AP)encompasses a spectrum of pancreatic inflammatory conditions,ranging from mild inflammation to severe pancreatic necrosis and multisystem organ failure.Given the challenges associated ...BACKGROUND Acute pancreatitis(AP)encompasses a spectrum of pancreatic inflammatory conditions,ranging from mild inflammation to severe pancreatic necrosis and multisystem organ failure.Given the challenges associated with obtaining human pancreatic samples,research on AP predominantly relies on animal models.In this study,we aimed to elucidate the fundamental molecular mechanisms underlying AP using various AP models.AIM To investigate the shared molecular changes underlying the development of AP across varying severity levels.METHODS AP was induced in animal models through treatment with caerulein alone or in combination with lipopolysaccharide(LPS).Additionally,using Ptf1αto drive the specific expression of the hM3 promoter in pancreatic acinar cells transgenic C57BL/6J-hM3/Ptf1α(cre)mice were administered Clozapine N-oxide to induce AP.Subsequently,we conducted RNA sequencing of pancreatic tissues and validated the expression of significantly different genes using the Gene Expression Omnibus(GEO)database.RESULTS Caerulein-induced AP showed severe inflammation and edema,which were exacerbated when combined with LPS and accompanied by partial pancreatic tissue necrosis.Compared with the control group,RNA sequencing analysis revealed 880 significantly differentially expressed genes in the caerulein model and 885 in the caerulein combined with the LPS model.Kyoto Encyclopedia of Genes and Genomes enrichment analysis and Gene Set Enrichment Analysis indicated substantial enrichment of the TLR and NOD-like receptor signaling pathway,TLR signaling pathway,and NF-κB signaling pathway,alongside elevated levels of apoptosis-related pathways,such as apoptosis,P53 pathway,and phagosome pathway.The significantly elevated genes in the TLR and NOD-like receptor signaling pathways,as well as in the apoptosis pathway,were validated through quantitative real-time PCR experiments in animal models.Validation from the GEO database revealed that only MYD88 concurred in both mouse pancreatic tissue and human AP peripheral blood,while TLR1,TLR7,RIPK3,and OAS2 genes exhibited marked elevation in human AP.The genes TUBA1A and GADD45A played significant roles in apoptosis within human AP.The transgenic mouse model hM3/Ptf1α(cre)successfully validated significant differential genes in the TLR and NOD-like receptor signaling pathways as well as the apoptosis pathway,indicating that these pathways represent shared pathological processes in AP across different models.CONCLUSION The TLR and NOD receptor signaling pathways play crucial roles in the inflammatory progression of AP,notably the MYD88 gene.Apoptosis holds a central position in the necrotic processes of AP,with TUBA1A and GADD45A genes exhibiting prominence in human AP.展开更多
Acute pancreatitis(AP)is a common gastrointestinal disorder.Approximately15%-20%of patients develop severe AP.Systemic inflammatory response syndrome and multiple organ dysfunction syndrome may be caused by the massiv...Acute pancreatitis(AP)is a common gastrointestinal disorder.Approximately15%-20%of patients develop severe AP.Systemic inflammatory response syndrome and multiple organ dysfunction syndrome may be caused by the massive release of inflammatory cytokines in the early stage of severe AP,followed by intestinal dysfunction and pancreatic necrosis in the later stage.A study showed that 59%of AP patients had associated intestinal barrier injury,with increased intestinal mucosal permeability,leading to intestinal bacterial translocation,pancreatic tissue necrosis and infection,and the occurrence of multiple organ dysfunction syndrome.However,the real effect of the gut microbiota and its metabolites on intestinal barrier function in AP remains unclear.This review summarizes the alterations in the intestinal flora and its metabolites during AP development and progression to unveil the mechanism of gut failure in AP.展开更多
The kinetic processes of Xe(6p[1/2]0, 6p[3/2]2, and 6p[5/2]2) atoms under the focused condition were investigated. The atomic density of the laser prepared state significantly increases. Therefore, the probability of ...The kinetic processes of Xe(6p[1/2]0, 6p[3/2]2, and 6p[5/2]2) atoms under the focused condition were investigated. The atomic density of the laser prepared state significantly increases. Therefore, the probability of the energy-pooling between two high-lying atoms increases. There are three major types of the energy-pooling collisions. The first type is the energy-pooling ionization. Once the excitation laser is focused, the obvious ionization can be observed from the side window whenever the laser prepared state is 6p[1/2]0, 6p[3/2]2, or 6p[5/2]2 state. Ionization of Xe is attributed to the energy-pooling ionization or a Xe* atom reabsorbing another excitation photon. The second type is energy-pooling with big energy difference. When the 6p[1/2]0 state is the laser prepared state, the energy-pooling collision between two 6p[1/2]0 atoms can produce one 5d[3/2]1 atom and one 6s'[1/2]0 atom. The third type is energy-pooling with small energy difference. The intensities of fluorescence lines are much stronger that five secondary 6p states act as the upper states, and the rising edges of these fluorescence lines are much steeper. The primary mechanism of generating the secondary 6p atoms is energy-pooling collision instead of collision relaxation. Based on the collision probability, the rate of energy-pooling between two 6p[1/2]0 atoms is deduced (6.39x10^8s-1). In addition, the 6s atoms also increase under the focused condition. Therefore, all the fluorescence lines are serious trailing by radiation trapping.展开更多
基金Supported by National Natural Science Foundation of China,No.82260133 and No.82370661the Academic and Technical Leader of major disciplines in Jiangxi Province,No.20225BCJ23021+2 种基金the Jiangxi Medicine Academy of Nutrition and Health Management,No.2022-PYXM-01the Natural Science Foundation of Jiangxi Province,No.20224ACB216004the Technological Innovation Team Cultivation Project of the First Affiliated Hospital of Nanchang University,No.YFYKCTDPY202202.
文摘BACKGROUND Acute pancreatitis(AP)encompasses a spectrum of pancreatic inflammatory conditions,ranging from mild inflammation to severe pancreatic necrosis and multisystem organ failure.Given the challenges associated with obtaining human pancreatic samples,research on AP predominantly relies on animal models.In this study,we aimed to elucidate the fundamental molecular mechanisms underlying AP using various AP models.AIM To investigate the shared molecular changes underlying the development of AP across varying severity levels.METHODS AP was induced in animal models through treatment with caerulein alone or in combination with lipopolysaccharide(LPS).Additionally,using Ptf1αto drive the specific expression of the hM3 promoter in pancreatic acinar cells transgenic C57BL/6J-hM3/Ptf1α(cre)mice were administered Clozapine N-oxide to induce AP.Subsequently,we conducted RNA sequencing of pancreatic tissues and validated the expression of significantly different genes using the Gene Expression Omnibus(GEO)database.RESULTS Caerulein-induced AP showed severe inflammation and edema,which were exacerbated when combined with LPS and accompanied by partial pancreatic tissue necrosis.Compared with the control group,RNA sequencing analysis revealed 880 significantly differentially expressed genes in the caerulein model and 885 in the caerulein combined with the LPS model.Kyoto Encyclopedia of Genes and Genomes enrichment analysis and Gene Set Enrichment Analysis indicated substantial enrichment of the TLR and NOD-like receptor signaling pathway,TLR signaling pathway,and NF-κB signaling pathway,alongside elevated levels of apoptosis-related pathways,such as apoptosis,P53 pathway,and phagosome pathway.The significantly elevated genes in the TLR and NOD-like receptor signaling pathways,as well as in the apoptosis pathway,were validated through quantitative real-time PCR experiments in animal models.Validation from the GEO database revealed that only MYD88 concurred in both mouse pancreatic tissue and human AP peripheral blood,while TLR1,TLR7,RIPK3,and OAS2 genes exhibited marked elevation in human AP.The genes TUBA1A and GADD45A played significant roles in apoptosis within human AP.The transgenic mouse model hM3/Ptf1α(cre)successfully validated significant differential genes in the TLR and NOD-like receptor signaling pathways as well as the apoptosis pathway,indicating that these pathways represent shared pathological processes in AP across different models.CONCLUSION The TLR and NOD receptor signaling pathways play crucial roles in the inflammatory progression of AP,notably the MYD88 gene.Apoptosis holds a central position in the necrotic processes of AP,with TUBA1A and GADD45A genes exhibiting prominence in human AP.
基金Supported by the National Natural Science Foundation of China,No.81760120 and No.81960128the Key Program of Science and Technology Department of Jiangxi Province,No.20171BBG70084 and No.20192ACBL20037.
文摘Acute pancreatitis(AP)is a common gastrointestinal disorder.Approximately15%-20%of patients develop severe AP.Systemic inflammatory response syndrome and multiple organ dysfunction syndrome may be caused by the massive release of inflammatory cytokines in the early stage of severe AP,followed by intestinal dysfunction and pancreatic necrosis in the later stage.A study showed that 59%of AP patients had associated intestinal barrier injury,with increased intestinal mucosal permeability,leading to intestinal bacterial translocation,pancreatic tissue necrosis and infection,and the occurrence of multiple organ dysfunction syndrome.However,the real effect of the gut microbiota and its metabolites on intestinal barrier function in AP remains unclear.This review summarizes the alterations in the intestinal flora and its metabolites during AP development and progression to unveil the mechanism of gut failure in AP.
基金supported by the National Natural Science Foundation of China(No.11475177 and No.61505210)Key Laboratory of Chemical Laser Foundation(KLCL 2017)
文摘The kinetic processes of Xe(6p[1/2]0, 6p[3/2]2, and 6p[5/2]2) atoms under the focused condition were investigated. The atomic density of the laser prepared state significantly increases. Therefore, the probability of the energy-pooling between two high-lying atoms increases. There are three major types of the energy-pooling collisions. The first type is the energy-pooling ionization. Once the excitation laser is focused, the obvious ionization can be observed from the side window whenever the laser prepared state is 6p[1/2]0, 6p[3/2]2, or 6p[5/2]2 state. Ionization of Xe is attributed to the energy-pooling ionization or a Xe* atom reabsorbing another excitation photon. The second type is energy-pooling with big energy difference. When the 6p[1/2]0 state is the laser prepared state, the energy-pooling collision between two 6p[1/2]0 atoms can produce one 5d[3/2]1 atom and one 6s'[1/2]0 atom. The third type is energy-pooling with small energy difference. The intensities of fluorescence lines are much stronger that five secondary 6p states act as the upper states, and the rising edges of these fluorescence lines are much steeper. The primary mechanism of generating the secondary 6p atoms is energy-pooling collision instead of collision relaxation. Based on the collision probability, the rate of energy-pooling between two 6p[1/2]0 atoms is deduced (6.39x10^8s-1). In addition, the 6s atoms also increase under the focused condition. Therefore, all the fluorescence lines are serious trailing by radiation trapping.
