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Objective:To investigate the role and possible pathogenesis of high mobility group protein B1 (HMGB1) in lipopolysaccharide (LPS)-induced acute lung injury/acute respiratory distress syndrome (ALI/ARDS).Methods:① In vivo, 24 SPFC57BL/6 male mice were randomly divided into normal control group, ALI/ARDS model group, ethyl pyruvate (EP) treatment group and EP control group, with 6 mice in each group. The ALI/ARDS model was established by intraperitoneal injection of 20 mg/kg LPS. Mice in normal control group and EP control group were intraperitoneally injected with the same amount of sterile normal saline. Then, mice in the EP treatment group and EP control group were intraperitoneally injected with 40 mg/kg HMGB1 inhibitor EP. After 6 hours, the mice were sacrificed and lung tissues were collected. The expressions of heparan sulfate (HS), syndecans-1 (SDC-1), heparanase (HPA) and matrix metalloproteinases-9 (MMP-9) in lung tissues were detected by immunofluorescence technique. Orbital blood of mice was collected and serum was extracted to detect the content of HMGB1 by enzyme linked immunosorbent assay (ELISA). ② In vitro, human umbilical vein endothelial cells (HUVECs) were randomly divided into 6 groups: normal control group, HUVECs damage group (treated with 1 mg/L LPS for 6 hours), HMGB1 group (treated with 1 μmol/L recombinant HMGB1 for 6 hours), HMGB1+EP group (treated with recombinant HMGB1 for 1 hour and then added 1 μmol/L EP for 6 hours), LPS+EP group (treated with LPS for 1 hour and then added 1 μmol/L EP for 6 hours), EP group (treated with 1 μmol/L EP for 6 hours). The expressions of HS, SDC-1, HPA and MMP-9 in endothelial cells were detected by immunofluorescence technique. Results:① In vivo, light microscopy showed that the alveolar space was thickened after LPS stimulation, and there were a large number of inflammatory cells infiltrating in the alveolar space. Compared with ALI/ARDS model group, the expressions of HS and SDC-1 in lung tissue of EP treatment group were significantly increased [HS (fluorescence intensity): 0.80±0.20 vs. 0.53±0.02, SDC-1 (fluorescence intensity): 0.72±0.02 vs. 0.51±0.01, both P < 0.05], and the expressions of HPA and MMP-9 were significantly decreased [HPA (fluorescence intensity): 2.36±0.05 vs. 3.00±0.04, MMP-9 (fluorescence intensity): 2.55±0.13 vs. 3.26±0.05, both P < 0.05]; there were no significant changes of the above indexes in EP control group. Compared with ALI/ARDS model group, the content of serum HMGB1 in EP treatment group decreased significantly (μg/L: 131.88±16.67 vs. 341.13±22.47, P < 0.05); there was no significant change in the EP control group. ② In vitro, compared with HMGB1 group, the expressions of HS and SDC-1 in HMGB1+EP group were significantly higher [HS (fluorescence intensity): 0.83±0.07 vs. 0.56±0.03, SDC-1 (fluorescence intensity): 0.80±0.01 vs. 0.61±0.01, both P < 0.05], and the expressions of HPA and MMP-9 were significantly lower [HPA (fluorescence intensity): 1.30±0.02 vs. 2.29±0.05, MMP-9 (fluorescence intensity): 1.55±0.04 vs. 2.50±0.06, both P < 0.05]; the expression of HS, SDC-1, HPA and MMP-9 had no significant changes in EP group. Conclusion:HMGB1 participates in LPS-induced injury of endothelial cell glycocalyx, leading to increased lung permeability, and inhibition of HMGB1 can alleviate lung injury.
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Sulfonylureas are widely used oral anti-diabetic drugs. However, its long-term usage effects on patients' lifespan remain controversial, with no reports of influence on animal longevity. Hence, the anti-aging effects of chlorpropamide along with glimepiride, glibenclamide, and tolbutamide were studied with special emphasis on the interaction of chlorpropamide with mitochondrial ATP-sensitive K+ (mitoK-ATP) channels and mitochondrial complex II. Chlorpropamide delayed aging in Caenorhabditis elegans, human lung fibroblast MRC-5 cells and reduced doxorubicin-induced senescence in both MRC-5 cells and mice. In addition, the mitochondrial membrane potential and ATP levels were significantly increased in chlorpropamide-treated worms, which is consistent with the function of its reported targets, mitoK-ATP channels. Increased levels of mitochondrial reactive oxygen species (mtROS) were observed in chlorpropamide-treated worms. Moreover, the lifespan extension by chlorpropamide required complex II and increased mtROS levels, indicating that chlorpropamide acts on complex II directly or indirectly via mitoK-ATP to increase the production of mtROS as a pro-longevity signal. This study provides mechanistic insight into the anti-aging effects of sulfonylureas in C. elegans.
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Objective To study the relationship between essential hypertension(EH)with serum homocysteine(HCY),uroten-sinⅡ(UⅡ),angiotensin converting enzyme(ACE)and N-terminal pro-brain natriuretic peptide(NT-proBNP).Methods By collec-ting the clinical cases,UⅡwas determined by ELISA and HCY,ACE and NT-proBNP were simultaneously detected by ELISA.The detection results were analyzed and compared between the patients with essential hypertension(EH group)and the healthy con-trols.Results The levels of serum HCY,UⅡ,ACE and NT-proBNP in the EH group were significantly increased compared with the healthy control group;the area under curve (AUC)of serum HCY,UⅡ,ACE and NT-proBNP in the ROC curve in the EH group were 0.93,0.765,0.792 and 0.972 respectively,which showed clinical diagnostic significance.Conclusion The levels of HCY,UⅡ,ACE and NT-proBNP are highly expressed in EH and have significant differences compared with the healthy popula-tion,which has the diagnostic value to EH.
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Objective To explore applied characteristics of the prolene hernia system(PHS) in inguinal hernioplasty, and management during and after operation, and long-term effect of this kind of hemioplasty in aged patients. Methods 69 aged patients using PHS were followed and analyzed retrospectively. Results Tension-free inguinal hernioplasty with the PHS were performed in 69 aged patients of groin hernia. Operative time ranged from 45min to 160min. Post-operatively, 3 patients developed gentle scrotal swelling, and 20 patients had been adminis- tered anodyne for pain of incision, and 12 cases experienced retention of urine, 1 case developed pneumonia, and 2 cases oeeurred incisional infection and gore. 68 cases of them recovered daily life about 2 to 3 weeks after operation. During follow-up period from 6 months to 77 months,there was no recurrence of inguinal hernia and no pain in in-guinal region, but 2 patients feel discomfort sporadically. Conclusion The PHS strengthens the myopectineal orifice and seals up-area of it,so the system is especially preferred in treating aged patients of groin hernias who have some defectsof anatomic structure in inguinal region. The local anaesthesia is also suitable for this kind of hernioplasty in aged patients.
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Objective: To observe the effects of ginaton and nitroglycerin injection on expression of heat shock protein 70 (HSP70) and cardioprotective mechanism in rabbits with ischemia/reperfusion (I/R). Methods : Twenty New Zealand white rabbits were randomly divided into four groups, 5 rabbits being in each group. The model was not replicated in the sham-operated group. Myocardial I/R models were replicated in animals in normal saline, ginatone and nitroglycerin injection groups and were administered with normal saline, ginatone and nitroglycerin injection respectively 0.5 hour before ischemia. Western blot was used to measure HSP70 of ischemia and non-ischemia myocardium and the expression of HSP70 was analyzed semiquantitatively . Serum nitric oxide (NO), malondialdehyde (MDA) contents and total superoxide dismutase (TCD*2SOD) , creatine kinase (CK) activity were measured. Results: HSP70 was less expressed in sham-operated group and more expressed in normal saline group, ginaton group and nitroglycerin injection group. Expression of HSP70 of ischemia and non-ischemia myocardium in normal saline group was 2.5CD*2 and 2.1CD*2fold, in ginaton group 17.6CD*2 and 20.7CD*2fold and in nitroglycerin group 28.1CD*2 and 29.1CD*2fold to that in the shamCD*2operated group, respectively. The activity of TCD*2SOD was lower while MDA and CK levels were higher in the normal saline group than those in the sham-operated group (all P