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Didymin Alleviates Cerebral Ischemia-Reperfusion Injury by Activating the PPAR Signaling Pathway
Qiang Li,Hongting Zhang,Xiumei Liu 연세대학교의과대학 2022 Yonsei medical journal Vol.63 No.10
Purpose: Cerebral ischemia-reperfusion (IR) injury is a severe secondary injury induced by reperfusion after stroke. Didymin has been reported to have a protective effect on intracerebral hemorrhage. However, the underlying mechanism of didymin on regu lating cerebral IR injury remains largely unknown. Materials and Methods: A rat cerebral IR model and oxygen-glucose deprivation/reperfusion (OGD/R) model in PC12 cells were established. Hematoxylin and eosin (H&E) was used to detect the pathological changes in brain tissues, and TUNEL staining was performed to detect apoptosis of brain tissues. MTT and flow cytometry were used to measure the viability and apoptosis of PC12 cells. QRT-PCR and western blot were used to detect inflammation cytokines in PC12 cells. Western blot was used to measure the expression of PPAR-γ, RXRA, Bax, c-caspase-3, and Bcl-2. Results: Didymin pretreatment decreased apoptotic rates, reduced levels of Bax and c-caspase-3, and increased Bcl-2 level in vivo and in vitro. Additionally, didymin pretreatment increased viability and decreased the inflammation levels [interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, and monocyte chemotactic protein (MCP)-1] of OGD/R treated PC12 cells. Moreover, did ymin activated the peroxisome proliferator-activated receptors (PPAR) signaling pathway and increased the expression of PPAR-γ and RXRA in OGD/R treated PC12 cells. Inhibition of PPAR-γ eliminated the protective effect of didymin on OGD/R treated cells. Conclusion: Didymin protected neuron cells against IR injury in vitro and in vivo by activation of the PPAR pathway. Didymin may be a candidate drug for IR treatment.
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Qian Dong,Buxian Jiang,Hong Zhang,Zhong Jiang,Hongting Lu,Chuanmin Yang,Yu Cheng,Xiwei Hao 연세대학교의과대학 2006 Yonsei medical journal Vol.47 No.6
The purpose of this study was to investigate and discuss imaging methods and management strategies for congenital choledochal cyst with co-existing intrahepatic dilation and aberrant bile duct as well as other complicated biliary anomalies. In this study we reviewed and analyzed 72 patients with congenital choledochal cyst, ranging in age from 15 days to 12 years old and who were seen at our hospital during the past 12 years, from January 1993 to October 2005. The image manifestation and clinical significance of patients with co- xisting intrahepatic biliary dilation and aberrant bile duct were carefully examined during operation via MRCP, cholangiography and choledochoscope. Twenty-two cases (30.1%) presented with intrahepatic bile duct dilation and 12 of these were of the cystic type. That is, the orifice of the dilated intrahepatic tract that converged into the common hepatic duct showed membrane or septum-like stenosis. In 10 cases the dilation tapered off from the porta hepatis to the initiating terminals of the intra-hepatic bile ducts and was not accompanied by stenosis. An aberrant bile duct was observed in 2 of the cases. In 3 cases, the right and left hepatic ducts converged at the choledochal cyst. In conclusion, the imaging methods for intrahepatic bile duct dilation possess important clinical significance. Further, for hepatojejunostomy with radical excision of a choledochal cyst, additional operative procedures for intrahepatic stenosis, possible bile duct malformation and pancreaticobiliary common duct calculi can potentially reduce postoperative complications.
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Dihua Wu,Xiru Zhang,Yujie Chen,Sanchuan Yu,Hongting Zhao 한국화학공학회 2020 Korean Journal of Chemical Engineering Vol.37 No.2
Thin film composite polyesteramide nanofiltration membranes were fabricated with interfacial polymerization from carboxylated chitosan and trimesoyl chloride on a microporous polysulfone support membrane. Salt rejection was improved by building a multiple-layer structure that was formed by sequentially repeating the cycles of the interfacial reactions. The chemical structure, surface morphology and charge were characterized for the polyesteramide top layer. The effects of the concentrations of the reactant solutions and the number of cycles of reactant depositions and reactions on the separation performance were investigated. The single-layer polyesteramide membrane produced from 3.5 wt% carboxylated chitosan and 0.7 wt% TMC has a negatively charged surface and shows favorable separation performance: pure water permeation flux of 7.3 L/(m2 h) at 0.6MPa gauge feed pressure, and salt rejection of 95.0% for Na2SO4, 65.7% for MgSO4, 33.2% for MgCl2 and 66.3% for NaCl. The multiple-layer polyesteramide membranes show a more negatively charged surface and higher salt rejection than the single-layer polyesteramide membranes. The single-layer polyesteramide membrane PS-[(C-CS)1.0/TMC] with a relatively loose structure shows good retention for the reactive black 5 anionic dye. This study opens an interesting research area to explore a new type of thin film composite nanofiltration membrane.
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Pituitary P62 deficiency leads to female infertility by impairing luteinizing hormone production
Li Xing,Zhou Ling,Peng Guiliang,Liao Mingyu,Zhang Linlin,Hu Hua,Long Ling,Tang Xuefeng,Qu Hua,Shao Jiaqing,Zheng Hongting,Long Min 생화학분자생물학회 2021 Experimental and molecular medicine Vol.53 No.-
P62 is a protein adaptor for various metabolic processes. Mice that lack p62 develop adult-onset obesity. However, investigations on p62 in reproductive dysfunction are rare. In the present study, we explored the effect of p62 on the reproductive system. P62 deficiency-induced reproductive dysfunction occurred at a young age (8 week old). Young systemic p62 knockout (p62 -/- ) and pituitary-specific p62 knockout (p62 flox/flox αGSU cre ) mice both presented a normal metabolic state, whereas they displayed infertility phenotypes (attenuated breeding success rates, impaired folliculogenesis and ovulation, etc.) with decreased luteinizing hormone (LH) expression and production. Consistently, in an infertility model of polycystic ovary syndrome (PCOS), pituitary p62 mRNA was positively correlated with LH levels. Mechanistically, p62 -/- pituitary RNA sequencing showed a significant downregulation of the mitochondrial oxidative phosphorylation (OXPHOS) pathway. In vitro experiments using the pituitary gonadotroph cell line LβT2 and siRNA/shRNA/plasmid confirmed that p62 modulated LH synthesis and secretion via mitochondrial OXPHOS function, especially Ndufa2, a component molecule of mitochondrial complex I, as verified by Seahorse and rescue tests. After screening OXPHOS markers, Ndufa2 was found to positively regulate LH production in LβT2 cells. Furthermore, the gonadotropin-releasing hormone (GnRH)-stimulating test in p62 flox/flox αGSU cre mice and LβT2 cells illustrated that p62 is a modulator of the GnRH-LH axis, which is dependent on intracellular calcium and ATP. These findings demonstrated that p62 deficiency in the pituitary impaired LH production via mitochondrial OXPHOS signaling and led to female infertility, thus providing the GnRH-p62-OXPHOS(Ndufa2)-Ca 2+ /ATP-LH pathway in gonadotropic cells as a new theoretical basis for investigating female reproductive dysfunction.
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