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AIM: To investigate the effect of autophagy on cell ferroptosis in intestinal ischemia-reperfusion injury. METHODS: Twenty-four SPF grade Wistar rats weighing 200-220 g were divided into 4 groups (n = 6): sham operation group (sham group), ischemia group (I group), ischemia-reperfusion group (I/R group),and ischemia-reperfusion + autophagy inhibitor group (I/R + 3-MA group). The ischemia model was established by clamping the superior mesenteric artery for 1 hour, and the intestinal ischemia-reperfusion injury model was established by reperfusion for 2 hours. HE staining was used to observe the pathological changes of intestinal mucosa and Chiu score under light microscope. Fe
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AIM: To investigate the effect of dapagliflozin on myocardial injury in type 1 diabetes mice and its mechanism. METHODS: Normal C57BL / 6J male mice were randomly divided into normal control group (Control), diabetes cardiomyopathy group (DCM) and dapagliflozin group (DAPA). The model of diabetes was induced by streptozotocin (STZ) and given maintenance feed. DAPA group was given 10 mg · kg
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Intestinal ischemia/reperfusion injury (ll/RI) is a common pathological process in clinical practice. Ischemia/reperfusion causes damage to intestinal mucosa and distant organs, and induces systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndrome (MODS). Autophagy is a defense regulation mechanism under stress conditions, which can maintain the homeostasis of cytoplasm, proteins and organelles. The mechanism of autophagy is complex, which is Intestinal ischemia/reperfusion injury (II/RI) is a common pathological process in clinical practice. Ischemia/reperfusion causes damage to intestinal mucosa and distant organs, and induces systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndrome (MODS). Autophagy is a defense regulation mechanism under stress conditions, which can maintain the homeostasis of cytoplasm, proteins and organelles. The mechanism of autophagy is complex, which is co-regulated by protein complexes encoded by evolutionarily conserved autophagy-related gene (ATG) and a variety of signaling molecules and pathways. Studies have found that autophagy is involved in the process of intestinal ischemia-reperfusion injury. Therefore, revealing the mechanism of autophagy in II/RI can provide evidence for the prevention and treatment of II/RI.
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Pyroptosis is a newly discovered programmed cell death that can lead to inflammatory response, its occurrence depends on the sequential activation of inflammatory bodies and caspase, and then the pore-forming generated by the fragmentation of gasdermin D and its cell membrane polymerization. Pyroptosis is mainly comprised of the pathway that depends on caspase-1 activated by flammasomes and the non-classical pathway that depends on caspase-4/5/11 activated by cytoplasmic lipopolysaccharide. As an important mechanism mediating the inflammatory response of the body, pyroptosis plays an irreplaceable role in the body's response to noxious stimuli, which is closely related to many diseases such as nervous system diseases, cardiovascular system diseases and tumors. Recent studies have found that pyroptosis also plays a key role in the occurrence of intestinal ischemia-reperfusion (II/RI). This paper reviews the molecular characteristics, mechanism of pyroptosis and its relationship with II/RI in recent years, in order to provide theoretical basis for the prevention and treatment of II/RI.
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Objective To study the inhibitory effect of curcumin on the proliferation,migration and invasion of non-small cell lung cancer cell A549,and to discuss further if it is closely related to the expression of c-Jun N-terminal kinase (JNK) and relative protein p38.Methods A549 cells were cultured by conventional method,and then treated with different concentration of curcumin (10,20,40,80 μmol · L-1).The proliferation,migration and invasion of A549 cells were measured by real-time cellular analysis (RTCA).The expression levels of JNK,p-JNK,p38 and P-p38 were detected by real-time PCR and Western blotting.Results Curcumin showed an antiproliferation effect against A549 cells with IC50 =40 μmol · L-1,and curcumin exhibited obviously inhibitory effect on the migration and invasion of A549 cells.Additionally,compared with control group,curcumin suppressed the expression of JNK and p38 at the gene level,and significantly inhibited the expression of JNK,P-JNK,p38 and p38 (P＜0.05) at the protein level.Conclusion These results demonstrated that curcumin can inhibit the proliferation,migration and invasion of A549 cells via reducing the level of JNK,p38 phosphorylation,and blocking JNK signal transduction pathway.
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Objective To investigate the influence of curcumin and its analogue H8 on glucose and lipid metabolism disorder in db/db mice. Methods The type 2 diabetes mouse model (db/db mice) was intragastrically administrated with curcumin and analogue H8 for 8 weeks.The blood biochemical indexes were measured.The expression of PEPCK and G6Pase mRNA was detected by real-time PCR in liver tissues.The expression of PEPCK and G6Pase protein was detected by Western blotting. Results Curcumin analogue H8 reduced blood glucose and lipids in db/db mice (P<0.01) and improved liver function related enzymes significantly.The levels of PEPCK and G6Pase mRNA in db/db mice were significantly decreased (P<0.01) and the expression levels of PEPCK and G6Pase protein were significantly decreased(P<0.01). Conclusion Curcumin analogue H8 improves the glucose and lipid metabolism disorder in db/db mice,and it is related to inhibiting the expression of PEPCK and G6Pase gene and protein.
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Objective: To discuss the postoperative analgesia efficacy of multimodal analgesia of ropivacaine combined with dezocine, and to illuminate the feasibility of multimodal analgesia in the children undergoing cheiloplasty.Methods:In the randomized, controlled and double blind study, sixty children scheduled for cheiloplasty were randomly divided into ropivacaine group,dezocine group and multimodal analgesia group (n=20). The children in ropivacaine group and multimodal analgesia group were treated with infraobital nerve blockade (1.5 mL 0.25% ropivacaine)before skin incision.The children in dezocine group received the same volume of normal saline. The patients in dezocine group and the multimodal analgesia group received dezocine (0.15 mg·kg-1 )20 min before the end of operation, and the children in ropivacaine group received the same volume of normal saline.The children’s ages and weights,duration of anesthesia and operation, reviving and extubation time,agitation score and incidence,laryngospasm or bronchospasm,CRIES scores at 2,4,6,8,12, and 24 h after operation and adverse reactions were all recorded.Results:There were no significant differences in the age,weight,the duration of anesthesia and operation of the children between three groups (P >0.05).Compared with ropivacaine group,the reviving and extubation time of the children in dezocine group and multimodal analgesia group were increased (P 0.05).There were no laryngospasm or bronchospasm occured in all groups.The CRIES score at 2 h after operation of the children in multimodal analgesia group was the lowest and there were significant differences compared with other two groups (P 0.05).There were no significant differences in the CRIES scores at 8,12,and 24 h after operation between three groups (P > 0.05).Compared with other two groups,the incidence of tachycardia and the cases using analgesic in multimodal analgesia group were the lowest,and there were significant differences compared with other two groups (P < 0.05 ).There was no respiratory inhibition in all groups.Conclusion:The multimodal analgesia of ropivacaine combined with dezocine can effectively prolong the postoperative analgesia duration and reduce adverse reactions, and it can be safely used in the postoperative analgesia in the children undergoing cheiloplasty.
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Objective To determine the expression level of microRNA-25 in animal models of diabetic nephropathy and human renal tubular epithelial cells (HK-2) cultured in different conditions, and to explore its regulating effect on the fibrosis in diabetic nephropathy. Methods The expression of microRNA-25 was detected by real-time PCR. The downstream target protein of microRNA-25 was verified by bioinformatic prediction, transient transfection of cells and Western blotting. Results MicroRNA-25 was down-regulated in animal models of diabetic nephropathy and HK-2 cells which were cultured in high-glucose medium (P<0. 01). MAP2K4 might be the downstream target protein of microRNA-25. Overexpression of microRNA-25 reduced the protein expression of MAP2K4 and α-SMA (P<0. 01). Conclusion MicroRNA-25 inhibits the fibrosis in diabetic nephropathy by regulating the expression of MAP2K4.
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ObjectiveTo investigate the effect of mesenchymal stem cells (MSCs) transfected with hepatic growth factor (HGF) gene on the survival volume of free grain fat grafts.Methods MSCs of male Wistar rats were transfected with Ad-GFP or Ad-HGF.The transfection infectivity of Ad-GFP to MSCs,the expression of HGF were measured using ELISA assay.150 rats were randomly divided into 5 groups:control group (group A),MSCs group (group B),Ad HGF group (group C),MSCs transplanted with Ad-GFP group (group D),and MSCs transplanted with Ad-HGF (MSCsHGF) group (group E).Then,the same volume of frain fat graft,mixed with DMEM LG andMSCs,Ad HGF,MSCs-GFP,MSCs HGF respectively,were transplanted to rats back,but control group were only mixed with DMEM-LG.Fat graft was obtained on days 3,5,7,14,28,and 60 after implantation.The volume of fat graft was measured by messcylinder,and the expression of HGF and CD34 in transplanted fat tissue were detected by immunohistochemistry.ResultsThe transfection infectivity of Ad-GFP to MSCs was 89.6 ％ at 100 MOI,the expression of HGF in MSCs culture medium reached to the level after being transfected with Ad-HGF for 48 h.Compared with other 4 groups,at days 3,5,7,and 14 post-transplantation,the expression of HGF in E group transplanted fat of group E had statistics significance (P＜0.05).The persentage of survival volume of fat graft in group E was significantly higher than that of other group ( P＜0.05) at days 28,and 60 post transplantation.ConclusionsMSCs transplanted with Ad-HGF could secrete HGF and increase the survival volume of fat grafts.