[Effects of postconditioning on autophagy of lung ischemic reperfusion injury in rats].

OBJECTIVE: To explore the effects of postconditioning on autophagy of lung injury in situ during lung ischemic reperfusion. METHODS: Twenty-four male Sprague-Dawley rats were randomly divided into 3 groups of sham-operated (S), ischemic-reperfusion (I/R) and ischemic postconditioning (IpostC) (n = 8 each). All underwent left thoracotomy after anesthesia. In the S group, a line was only placed around left hilum but not fastened. In the I/R group, a line was fastened to block the blood flow of left lung for 30 min and then loosened for reperfusion for 120 min. In the IpostC group, after blocking the blood flow of left lung for 30 min, left hilum was fastened for 30 sec and loosened for 30 sec. Lung tissues were measured by Western blot. Histopathological changes of lung tissues were observed, lung injury scores calculated and autophagic vacuoles determined by electron microscope. RESULTS: The relative expression levels of mammalian target of rapamycin (mTOR) and phosphorylated mTOR (p-mTOR) in group I/R (0.40 ± 0.03, 0.33 ± 0.10) were not different with those of group S (0.37 ± 0.07, 0.31 ± 0.10) (both P > 0.05). However, both significantly increased in group IpostC (0.46 ± 0.09, 0.55 ± 0.07) (both P < 0.05). As compared with group S, the relative expression level of LC3-IIand lung injury score significantly increased in groups I/R and IpostC (0.53 ± 0.08, 0.38 ± 0.03 vs 0.25 ± 0.06; 15.79 ± 1.33, 11.67 ± 1.55 vs 5.58 ± 0.39) while obviously declined in group IpostC versus group I/R (all P < 0.05). In group I/R, neutrophil infiltration, interstitial edema, atelectasis and hyaline membrane formation were observed microscopically in lung tissues and the formation of autophagic vacuoles was evident under electron microscope. The changes of group IpostC were milder than those of group I/R. CONCLUSIONS: Ischemic postconditioning has protective effects on lung ischemic reperfusion injury by attenuating autophagy. It may be related with strengthening mTOR.

Exploration of pyroptosis-associated prognostic gene signature and lncRNA regulatory network in ovarian cancer.

Ovarian cancer (OC), is a tumor that poses a serious threat to women's health due to its high mortality rate and bleak prognosis. Pyroptosis, a type of programmed cell death, is important for determining the prognosis of a patient's prognosis for cancer and may represent a novel target for treatment. However, research into how prognosis is impacted by pyroptosis-related genes (PRGs) is poorly understood. In this study, a prognostic model was created using bioinformatic analysis of PRGs in OC. In OC, we discovered 18 pyroptosis regulators that were either up- or down-regulated. By analyzing prognoses, we developed a 9-genes based prognostic model. Each OC patient received a risk score that could be used to categorize them into two subgroups: those with high risk and/or low chance of survival and those with low risk and/or high chance of survival. Functional enrichment and immunoinfiltration analysis indicated that low expression of immune pathways in high-risk group may account for the decrease of survival possibility. In Multivariable cox regression studies, age, clinical stage and the prognostic model were discovered to be independent factors impacting the prognosis for OC. To forecast OC patient survival, a predictive nomogram was developed. Furthermore, we found a correlation between predictive PRGs and clinical stage, indicating that AIM2, CASP3, ZBP1 and CASP8 may play a role in the growth of tumor in OC. After detailed and complete bioinformatics analysis, the lncRNA RP11-186B7.4/hsa-miR-449a/CASP8/AIM2/ZBP1 regulatory axis was identified in OC. Our study may provide a novel approach for prognostic biomarkers and therapeutic targets of OC.

[Modulation of lung oxidant/antioxidant status by ischemic post-conditioning during ischemia/ reperfusion injury: experiment with rats].

OBJECTIVE: To investigate the effects of ischemic post-conditioning (IPO) on the lung endogenous oxidant-antioxidant system and nitric oxide level during the early stage of ischemia/reperfusion (I/R) injury. METHODS: Twenty four male Sprague-Dawley rats were randomly divided into 3 equal groups: sham-operation (S) group, I/R Group, undergoing ischemia by blocking the lung hilus for 1 h and then reperfusion for 30 min, IPO Group, undergoing blocking the lung hilus for 1 h and then 3 cycles of 10 s ischemia and 10 s reperfusion. Then the rats were killed with their lungs taken out. The levels of glutathione (GSH), nitric oxide (NO), malondialdehyde (MDA), xanthine oxidase (XO), and endogenous antioxidant enzymes, i. e, superoxide dismutase (SOD), and catalase (CAT), and activities of gultathionine peroxidase (GPX) and myeloperoxidase (MPO), a neutrophil accumulation marker, were measured respectively. RESULTS: In IPO group, Compared with I/R group, antioxidant systems such as the levels of SOD, CAT, GPX, and GSH of IPO Group were (41.4 +/- 4.4 ) U/mg, (19.5 +/- 1.6) U/mg, (168 +/- 13) U/mg, and (1.72 +/- 0.26) U/g, all significantly higher than those of I/R Group [(19.6 +/- 2.8) U/mg, (8.4 +/- 0.8) U/mg, (72 +/- 8) U/mg, and (0.89 +/-+/- 0.07) mg/g respectively, all P < 0.05); and the levels of XO, MPO, and MDA of Group IPO were (50 +/- 6) U/g, (5.0 +/- 0.5) U/g, and (0.91 +/- 0.08) nmol/mg respectively, all significantly lower than those of I/R Group [(83 +/- 8) U/g, (7.6 +/- 0.7) U/g and (1.58 +/- 0.17) nmol/mg respectively, all P < 0.05). The endogenous NO level of IPO Group was (93 +/- 7) micromol/g, significantly higher than that of I/R Group [(22 +/- 4) micromol/g, P < 0.01]. CONCLUSION: Post-conditioning at onset of reperfusion reduces lung I/R injury. The lung protection of IPO may be mediated, in part, by inhibiting the oxidant generation and oxidizing, and may be associated with the increasing of the endogenous NO level.

[Long-term outcome of lung cancer patients treated with surgical resection: A report of 210 cases].

BACKGROUND: To study the prognostic factors in patients with lung cancer after curative resection. METHODS: A retrospective study was conducted on 210 cases of clinicopathological survival data of lung cancer patients who underwent surgical resection from January 1987 to December 1999. Nine conventional prognostic factors were analyzed by COX model. RESULTS: The overall 3-, 5- and 10-year survival rates were 37.4%, 30.1% and 23.5% respectively. Univariate analysis showed that regional lymph nodes status (N), primary tumor status (T), histological type of lung cancer, the type of operation and curability of surgical resection were significantly related to disease specific survival. Multivariate analysis showed that regional lymph nodes status, primary tumor status and curability of surgical resection were the three independent predictors of long term outcome. The hazard ratio of death was 2.42 for patients with N2-3 vs N0-1( P =0.000 1), 3.50 for patients with T2-4 vs T1( P =0.033 0) and 1.77 for patients with incomplete resection vs complete resection ( P =0.022 4). CONCLUSIONS: Primary tumor status, regional lymph nodes status and curability of surgical resection are the three important prognostic factors of lung cancer. In order to improve long-term survival of lung cancer patients, it is very important to operate in the earlier stage of tumor, to extensively dissect intra-pulmonary and ipsilateral mediastinal lymph nodes and to avoid incomplete resection.

Induction of mucin secretion from human bronchial tissue and epithelial cells by rhinovirus and lipopolysaccharide.

AIM: To examine the effects of rhinovirus and lipopolysaccharide (LPS) on mucin secretion from bronchial tissue and epithelial cells in vitro. METHODS: Human small bronchial tissue fragments (HSBTF) and human bronchial epithelial cells (HBEC) were cultured with rhinovirus 16 and LPS, respectively and culture supernatants were collected for mucin measurement. To determine mucin levels in the culture supernatants, a MUC5AC enzyme linked immunosorbent assay and an enzyme linked lectin assay procedure with dolichos biflorus agglutinin (DBA) were developed, and mucin release was expressed as percentage increased (or decreased) secretion over baseline level. RESULTS: A concentration-dependent release of DBA mucin and MUC5AC mucin were observed when HSBTF were infected with various concentrations of rhinovirus 16 at 37 degree. The maximum-induced DBA mucin and MUC5AC mucin release were approximately 258 % and 83 % over baseline. The response of HSBTF to rhinovirus was completely abolished by metabolic inhibitors. Rhinovirus was also able to induce a concentration-dependent release of DBA mucin and MUC5AC mucin from primarily cultured HBEC. LPS 100 mg/L was able to provoke up to approximately 19 % and 54 % increase in DBA and MUC5AC mucin release over baseline, respectively from HSBTF, and 3.1 % and 57 % increase from HBEC at 20 h. Soybean trypsin inhibitor (SBTI) 30 mg/L was able to inhibit LPS-induced mucin release from HSBTF and HBEC. CONCLUSION: Rhinovirus is able to induce mucin secretion from human bronchial tissue and bronchial epithelial cells in vitro. LPS can induce MUC5AC mucin release from HSBTF and HBEC.