The present study aims to investigate the gastroprotective effect of Brucea javanica oil emulsion(BJOE) in animals. Gastroprotective potential of BJOE was studied on absolute ethanol,aspirin, reserpine and restraint p...The present study aims to investigate the gastroprotective effect of Brucea javanica oil emulsion(BJOE) in animals. Gastroprotective potential of BJOE was studied on absolute ethanol,aspirin, reserpine and restraint plus water immersion-induced gastric ulcers in mice as well as glacial acetic acid(GAA) and pyloric ligation(PL)-induced gastric ulcers in rats. Except for ulcer scores, total acidity as well as pepsin activity as for the PL-induced gastric ulcer model and ulcer incidence as for the GAA-induced gastric ulcer model were also determined. Histopathological evaluation as for aspirin, reserpine, PL-induced models was conducted. Results showed that BJOE significantly(P < 0.05) reduced ulcer index in the mouse and rat models in a dose-dependent manner. It had significant(P < 0.05) suppressive effect on total activity of gastric juice as well in PL-induced model. Histopathological examination for the stomach samples confirmed the findings in the aspirin, reserpine or PLinduced gastric lesion models, which showed relatively complete mucosa structure and less inflammation. It is concluded that BJOE could be effective on gastric ulcer in rodents and its gastroprotective activity might be related to antioxidant, anti-inflammatory ability and promote gastric mucus secreted. The results may provide beneficial basis for increasing BJOE's clinical indication in future.展开更多
Background: Necroptosis is a form of programmed cell death resulting in tissue inflammation due to the release of intracellular contents. Its role and regulatory mechanism in the context of acute lung injury (ALI) are...Background: Necroptosis is a form of programmed cell death resulting in tissue inflammation due to the release of intracellular contents. Its role and regulatory mechanism in the context of acute lung injury (ALI) are unclear. Parkin (Prkn), an E3 ubiquitin ligase, has recently been implicated in the regulation of necroptosis. In this study, we aimed to investigate the role and mechanism of Parkin in the process of ALI. Methods: Lipopolysaccharides (LPS)-induced mouse ALI model was utilized, and the pathological changes in lung tissues were characterized. To elucidate the roles of Parkin and necroptosis in this context, mixed lineage kinase domain-like ( Mlkl ) knockout mice, Prkn conditional knockout mice, and the necroptosis inhibitor were employed. Additionally, alveolar type 2 (AT2) cell-specific Parkin deletion and lineage-tracing mice were introduced to explore the specific roles and mechanisms of Parkin in AT2 cells. Results: A dose-dependent increase in Parkin expression in mouse lung tissues following LPS administration was observed, correlating with a shift from epithelial apoptosis to necroptosis. Notably, depletion of MLKL sig- nificantly mitigated the pathological changes associated with ALI, particularly the inflammatory response. Conversely, the deletion of Parkin exacerbated the injury pathology, significantly enhancing necroptosis, particularly in AT2 cells. This led to increased inflammation and post-LPS fibrosis. However, treatment with GSK872, a necroptosis inhibitor, substantially mitigated the phenotype induced by Parkin deletion. Importantly, Parkin deletion impaired the proliferation and differentiation of AT2 cells into AT1 cells. Conclusions: These findings underscore the multifaceted role of Parkin in the progression of lung injury, inflammation, and fibrosis through the regulation of AT2 cell necroptosis. Therefore, Parkin may hold potential as a therapeutic target for managing lung injury and fibrosis.展开更多
文摘The present study aims to investigate the gastroprotective effect of Brucea javanica oil emulsion(BJOE) in animals. Gastroprotective potential of BJOE was studied on absolute ethanol,aspirin, reserpine and restraint plus water immersion-induced gastric ulcers in mice as well as glacial acetic acid(GAA) and pyloric ligation(PL)-induced gastric ulcers in rats. Except for ulcer scores, total acidity as well as pepsin activity as for the PL-induced gastric ulcer model and ulcer incidence as for the GAA-induced gastric ulcer model were also determined. Histopathological evaluation as for aspirin, reserpine, PL-induced models was conducted. Results showed that BJOE significantly(P < 0.05) reduced ulcer index in the mouse and rat models in a dose-dependent manner. It had significant(P < 0.05) suppressive effect on total activity of gastric juice as well in PL-induced model. Histopathological examination for the stomach samples confirmed the findings in the aspirin, reserpine or PLinduced gastric lesion models, which showed relatively complete mucosa structure and less inflammation. It is concluded that BJOE could be effective on gastric ulcer in rodents and its gastroprotective activity might be related to antioxidant, anti-inflammatory ability and promote gastric mucus secreted. The results may provide beneficial basis for increasing BJOE's clinical indication in future.
基金supported by the National Natural Science Foundation of China(Nos.82370085 and 82170017 to CC)funding from the Zhejiang Province Public Welfare Fund Project(No.LY24H050003)+1 种基金the Discipline Cluster of Oncology at Wenzhou Medical University,China(No.Z1-2023004)startup research funds from both the Quzhou Affiliated Hospital and The First Affiliated Hospital of Wenzhou Medical University。
文摘Background: Necroptosis is a form of programmed cell death resulting in tissue inflammation due to the release of intracellular contents. Its role and regulatory mechanism in the context of acute lung injury (ALI) are unclear. Parkin (Prkn), an E3 ubiquitin ligase, has recently been implicated in the regulation of necroptosis. In this study, we aimed to investigate the role and mechanism of Parkin in the process of ALI. Methods: Lipopolysaccharides (LPS)-induced mouse ALI model was utilized, and the pathological changes in lung tissues were characterized. To elucidate the roles of Parkin and necroptosis in this context, mixed lineage kinase domain-like ( Mlkl ) knockout mice, Prkn conditional knockout mice, and the necroptosis inhibitor were employed. Additionally, alveolar type 2 (AT2) cell-specific Parkin deletion and lineage-tracing mice were introduced to explore the specific roles and mechanisms of Parkin in AT2 cells. Results: A dose-dependent increase in Parkin expression in mouse lung tissues following LPS administration was observed, correlating with a shift from epithelial apoptosis to necroptosis. Notably, depletion of MLKL sig- nificantly mitigated the pathological changes associated with ALI, particularly the inflammatory response. Conversely, the deletion of Parkin exacerbated the injury pathology, significantly enhancing necroptosis, particularly in AT2 cells. This led to increased inflammation and post-LPS fibrosis. However, treatment with GSK872, a necroptosis inhibitor, substantially mitigated the phenotype induced by Parkin deletion. Importantly, Parkin deletion impaired the proliferation and differentiation of AT2 cells into AT1 cells. Conclusions: These findings underscore the multifaceted role of Parkin in the progression of lung injury, inflammation, and fibrosis through the regulation of AT2 cell necroptosis. Therefore, Parkin may hold potential as a therapeutic target for managing lung injury and fibrosis.
