TNF-α and RPLP0 drive the apoptosis of endothelial cells and increase susceptibility to high-altitude pulmonary edema.

High-altitude pulmonary edema (HAPE) is a fatal threat for sojourners who ascend rapidly without sufficient acclimatization. Acclimatized sojourners and adapted natives are both insensitive to HAPE but have different physiological traits and molecular bases. In this study, based on GSE52209, the gene expression profiles of HAPE patients were compared with those of acclimatized sojourners and adapted natives, with the common and divergent differentially expressed genes (DEGs) and their hub genes identified, respectively. Bioinformatic methodologies for functional enrichment analysis, immune infiltration, diagnostic model construction, competing endogenous RNA (ceRNA) analysis and drug prediction were performed to detect potential biological functions and molecular mechanisms. Next, an array of in vivo experiments in a HAPE rat model and in vitro experiments in HUVECs were conducted to verify the results of the bioinformatic analysis. The enriched pathways of DEGs and immune landscapes for HAPE were significantly different between sojourners and natives, and the common DEGs were enriched mainly in the pathways of development and immunity. Nomograms revealed that the upregulation of TNF-α and downregulation of RPLP0 exhibited high diagnostic efficiency for HAPE in both sojourners and natives, which was further validated in the HAPE rat model. The addition of TNF-α and RPLP0 knockdown activated apoptosis signaling in endothelial cells (ECs) and enhanced endothelial permeability. In conclusion, TNF-α and RPLP0 are shared biomarkers and molecular bases for HAPE susceptibility during the acclimatization/adaptation/maladaptation processes in sojourners and natives, inspiring new ideas for predicting and treating HAPE.

Association of CD14 gene -260C>T and -561C>T polymorphisms with cancer susceptibility: A meta-analysis.

BACKGROUND: Two polymorphisms, -260C>T (rs2569190) and -561C>T (rs5744455), in the CD14 gene have been implicated in susceptibility to cancer. However, the results remain inconclusive. The current meta-analysis was carried out aiming to confirm the function of these two polymorphisms on the susceptibility of cancer. METHODS: We collected eligible studies from databases, including PubMed, EMBASE, CNKI, Wanfang, and VIP (Weipu). We used logistic regression calculation to compute odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: After strict selection, 24 studies with 5854 cases and 10339 controls for -260C>T and seven studies with 1809 cases and 7289 controls for -561C>T were finally enlisted into our analysis reference material. Pool results revealed that neither -260C>T, nor -561C>T was found to have any association with overall cancer susceptibility. Nevertheless, when stratified by cancer type, we detected a decreased risk associated with other cancers in a heterozygous model (OR = 0.69, 95% CI = 0.51-0.93, p = 0.014) and a dominant model (OR = 0.70, 95% CI = 0.53-0.93, p = 0.012) for -561C>T. An increased risk was found in other cancers under an allele model (OR = 1.29, 95% CI = 1.03-1.62, p = 0.026), in laryngeal cancer under a dominant model (OR = 1.38, 95% CI = 1.11-1.71, p = 0.003) and for a score ≤ 9 under a recessive model (OR = 1.45, 95% CI = 1.09-1.91, p = 0.009) for -561C>T. CONCLUSIONS: In the present study, we conclude that the CD14 -260C>T and -561C>T polymorphisms might not be associated with overall cancer risk. Further studies are encouraged to confirm this conclusion.

Protective effect of naringin against radiation-induced heart disease in rats via Sirt1/NF-κB signaling pathway and endoplasmic reticulum stress.

This study was designed to explore the protective effect and mechanism of naringin (NG) on radiation-induced heart disease (RIHD) in rats. Rats were divided into four x-ray (XR) irradiation groups with different absorbed doses (0/10/15/20 Gy), or into three groups (control, XR, and XR + NG groups). Subsequently, the ultrasonic diagnostic apparatus was adopted to assess and compare the left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS), left ventricular internal diameter at end diastole (LVIDd), and left ventricular internal diameter at end systole (LVIDs) in rats. Hematoxylin-eosin (H&E) staining and Masson staining were applied to detect the pathological damage and fibrosis of heart tissue. Western blot was used to measure the expression levels of myocardial fibrosis-related proteins, endoplasmic reticulum stress-related proteins, and Sirt1 (silent information regulator 1)/NF-κB (nuclear factor kappa-B) signaling pathway-related proteins in cardiac tissues. Additionally, enzyme-linked immunosorbent assay was utilized to detect the activities of pro-inflammatory cytokines, malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT) in cardiac tissue. The results showed that NG treatment significantly attenuated the 20 Gy XR-induced decline of LVEF and LVFS and the elevation of LVIDs. Cardiac tissue damage and fibrosis caused by 20 Gy XR were significant improved after NG treatment. Meanwhile, in rats irradiated by XR, marked downregulation was identified in the expressions of fibrosis-related proteins (Col I, collagen type I; α-SMA, α-smooth muscle actin; and TGF-ß1, transforming growth factor-beta 1) and endoplasmic reticulum stress-related proteins (GRP78, glucose regulatory protein 78; CHOP, C/EBP homologous protein; ATF6, activating transcription factor 6; and caspase 12) after NG treatment. Moreover, NG treatment also inhibited the production of pro-inflammatory cytokines [interleukin-6, interleukin-1ß, and monocyte chemoattractant protein-1 (MCP-1)], reduced the expression of MDA, and promoted the activities of SOD and CAT. Also, NG treatment promoted Sirt1 expression and inhibited p65 phosphorylation. Collectively, XR irradiation induced cardiac injury in rats in a dose-dependent manner. NG could improve the cardiac injury induced by XR irradiation by inhibiting endoplasmic reticulum stress and activating Sirt1/NF-κB signaling pathway.

[Clinical significance of detection of thrombus precursor protein in severe sepsis].

OBJECTIVE: To evaluate the significance of the changes in plasma thrombus precursor protein (TPP) in severe sepsis. METHODS: Enzyme linked immunoadsorbent assay (ELISA) was used in the determination of plasma TPP in 22 patients with severe sepsis group. Prothrombin time (PT), activated partial thromboplastin time(APTT), fibrin(Fib), D-Dimer were also determined and the values were compared with those obtained from 10 patients with infection and 8 healthy normal controls. At the same time, scores of sepsis related organ failure assessment(SOFA), simplified acute physiology score (SAPSII), Marshall criteria were made respectively in patients with severe sepsis on 1,3,5 days after admission to the ICU. Analysis of correlation between TPP and scores was done. RESULTS: (1)The concentration of TPP and positive rate of D-Dimer in severe sepsis were obviously higher than that in the ordinary infection group and normal control group (all P<0.05). But there were no differences in levels of PT, APTT, and Fib among three groups. (2)The concentration of TPP rose continuously in nonsurvivors due to severe sepsis, and it was positively correlated with scores of SOFA, SAPSII, Marshall criteria. CONCLUSION: TPP levels showed a higher specificity and sensitivity in detecting hypercoagulability state in severe than D-Dimer, PT, APTT, Fib assay. It can be used as a diagnostic and prognostic parameter for early hypercoagulability states and outcome of severe sepsis.

[Clinical significance of soluble selectins and matrix metalloproteinases-9 in patients after successful cardiopulmonary resuscitation].

OBJECTIVE: To investigate whether patients after successful cardiopulmonary resuscitation (CPR) exist elevated levels of soluble P-and E-selectin (sP-selectin, sE-selectin), matrix metalloproteinases-9 (MMP-9) and to evaluate the clinical significance of changes in these cytokine levels. METHODS: Plasma levels of sP-and sE-selectin, MMP-9 of 82 patients who survived >or=48 hours after CPR were determined on the second day after successful CPR. They were classified into different groups according to whether causing systemic inflammatory response syndrome (SIRS) and developing sepsis. Sixty-five non-critically ill patients were served as control group. RESULTS: Incidence of SIRS was 68.3% (56/82 cases) after successful CPR. Plasma levels of sP-selectin were higher in patients with SIRS compared with those in patients without SIRS or control group (all P<0.01). Plasma levels of sE-selectin and MMP-9 were not significantly different between patients with SIRS and without SIRS (all P>0.05), but were higher in both patient groups than those in the control group (all P<0.01) 43.9% of the patients developed sepsis within 1 week after CPR. Plasma levels of sP-selectin were higher in patients developing sepsis than those in patients without sepsis (P<0.05), but plasma levels of sE-selectin and MMP-9 were not significantly different between two groups (all P>0.05). Plasma levels of sE-selectin and MMP-9 were higher in nonsurvivors than those in survivors (both P<0.01), but plasma levels of sP-selectin were not significantly different between two groups (all P>0.05). CONCLUSION: SIRS is a frequent but unspecific finding after CPR with only minor impact on outcome. Determination of sP-and sE-selectin, MMP-9 early after CPR might help to identify patients at a high risk for sepsis or an adverse, respectively.

[Prospective study of systemic inflammatory response syndrome of patients with nosocomial G- bacteria infection].

OBJECTIVE: To study the characteristics of systemic inflammatory response syndrome (SIRS) of inpatients with nosocomial G- bacteria infection in order to find on effective treatment. METHODS: Eighty-two inpatients of SIRS with lower respiratory tract infection with G- bacteria were studied prospectively until discharge or death. They were divided into two groups: observation group (42 cases) and control group (40 cases). Bacteria culture of sputum and drug sensitivity was performed. Routine treatment was carried out in the control group, and rhubarb and antibiotics with lower endotoxin releasing property were given to the observation group. The course of SIRS, the incidence of MODS, and the mortality were compared. RESULTS: The duration with SIRS in observation group and control group was respectively (6.2+/-1.3) days and (7.4+/-1.2) days, u=3.91, P<0.05; the incidence of MODS was 11.4 percent and 32.3 percent, respectively, chi(2)=4.27, P<0.05. The mortality rates of the patients with SIRS in two groups were 8.6 percent and 29.0 percent, respectively. CONCLUSION: The results indicated that the treatment with rhubarb could obviously reduce the duration of SIRS compared with routine method. The same is true in the incidence of MODS and mortality rate.

[Protective effect and mechanism of morphine on acute myocardial ischemia/reperfusion injury in rats].

OBJECTIVE: To explore the protective effect of morphine and its mechanism on acute myocardial ischemia/reperfusion (AMIR) injury in rats, by the method of detecting calcitonin gene-related peptide (CGRP) and endothelin-1 (ET-1) levels, as well as myocardial infarct size. METHODS: Forty SD rats were randomly divided into four groups: ischemia/reperfusion group (n=10), morphine preconditioning group (n=10), morphine and naloxone hydrochloride group (n=10), and normal controls (n=10). The animal model of AMIR was established in rats. The left anterior descending branch (LAD) of rat coronary was tied and un-tied. Animals were then sacrificed and hearts were harvested to determine myocardial infarct size by 2, 3, 5-triphenyl tetrazolium chloride (TTC). Radioimmunoassay was used to detect CGRP and ET-1 levels in plasma, and routine method was used to measure creatine kinase isoenzyme (CK-MB) in serum. RESULTS: Plasma ET-1 and CGRP levels were increased significantly than that in normal controls in acute myocardial infarction (AMI) at 10 minutes of LAD tied (all P<0.01). Plasma ET-1 and CK-MB levels in morphine preconditioning group in AMIR at 45 hours of reperfusion were decreased significantly as compared with that in the same group in AMI at 10 minutes, and myocardial infarct size decreased significantly (all P<0.01), while, plasma CGRP levels were markedly increased. Significant differences in those parameters were found between morphine preconditioning group and morphine combined with naloxone hydrochloride group (all P<0.01). CONCLUSION: Intravenous morphine has protective effects on AMI by increased plasma CGRP level, decreased plasma ET-1 level, and reduced myocardial infarct size.

Curcumin inhibits expression of inhibitor of DNA binding 1 in PC3 cells and xenografts.

Inhibitor of DNA binding 1 (Id1) plays an important role in genesis and metastatic progression of prostate cancer. We previously reported that down regulation of Id1 by small interfering RNA could inhibit the proliferation of PC3 cells and growth of its xenografted tumors. Curcumin, the active ingredient of turmeric, has shown anti-cancer properties via modulation of a number of different molecular regulators. Here we investigated whether Id1 might be involved in the anti-cancer effects of curcumin in vivo and in vitro. We firstly confirmed that curcumin inhibited cell viability in a dose-dependent fashion, and induced apoptosis in PC3 cells, associated with significant decrease in the mRNA and protein expression of Id1. Similar effects of curcumin were observed in tumors of the PC3 xenografted mouse model with introperitoneal injection of curcumin once a day for one month. Tumor growth in mice was obviously suppressed by curcumin during the period of 24 to 30 days. Both mRNA and protein levels of Id1 were significantly down-regulated in xenografted tumors. Our findings point to a novel molecular pathway for curcumin anti-cancer effects. Curcumin may be used as an Id1 inhibitor to modulate Id1 expression.

BML-111, a lipoxin receptor agonist, ameliorates 'two-hit'-induced acute pancreatitis-associated lung injury in mice by the upregulation of heme oxygenase-1.

The objective of this study is to investigate the effects of BML-111 on acute pancreatitis-associated lung injury (APALI) induced by cerulein with subsequent an LPS administration in mice and its possible mechanisms. One hundred and twenty-eight mice were randomly allocated to four groups, namely the APALI group, the BML-111 pretreatment group, the BM-111 control group, and the control group. The 'two-hit' mice APALI model was established by intraperitoneal injection of cerulein 7 times at hourly intervals and Escherichia coli lipopolysaccharide (LPS) once after the last dose of cerulein immediately. The samples were taken at 3, 6, 12, and 24 h after the last injection. Serum levels of amylase, TNF-a, IL-1ß and IL-10, were determined. Histological score of the pancreas and lung, the wet/dry weight ratio, and heme oxygenase-1 (HO-1) expression in the lung were also evaluated. BML-111 pretreatment significantly reduced the serum levels of amylase, TNF-α, IL-1ß, the wet/dry weight ratio of lung, and the pathology injury scores of pancreas and lung, and the serum levels of IL-10 were markedly increased. The severity of pancreatic and lung histology were also significantly improved by the administration of BML-111, and the expressions of HO-1 in lung tissues also increased in the BML-111 group compared with those in the APALI group. In conclusion, BML-111 exerts protective effects on APALI induced by cerulein and LPS. In addition to its anti-inflammatory effects, the beneficial effects may also be due to the upregulation of HO-1 expression in the lung tissues.

Effects of α-methylnorepinephrine on cardiac function and myocardium at early stage of resuscitation in rabbits.

BACKGROUND: Recent studies have shown that α2-adrenergic agonists can reduce postresuscitation myocardial injury. This study was undertaken to observe changes of hemodynamics, myocardial injury markers cTnT and cardiac morphology by establishing a cardiopulmonary resuscitation model with rabbits, and to detect whether α-methyl norepinephrine (α-MNE) can reduce the myocardial injury after CPR and improve cardiac function. METHODS: Eighteen health rabbits, weighing 2.5-3.5 kg, both male and female, were provided by the Lanzhou Institute of Veterinary Medicine. After setting up a rabbit model of cardiopulmonary resuscitation, 18 rabbits were randomly divided into three groups. The rabbits in group A as an operation-control group were subjected to anesthesia, endotracheal intubation, and surgery without induction of ventricular fibrillation. The rabbits in group B as an epinephrine group were administered with 30 µg/kg epinephrineduring CPR. The rabbits in group C as a MNE group were administered with 100 µg/kg a-MNE during CPR. The left ventricular end-diastolic pressure (LVEDP), left ventricular pressure rise and fall rate (±dp/dt) and serum concentrations of BNP were measured. Statistical package of SPSS 10.0 was used for data analysis and significant differences between means were evaluated by ANOVA. RESULTS: Compared to group A, the LVEDP of other two groups increased respectively (P<0.01 all), and peak±dp/dt decreased in the other two groups (P<0.01). The increase of LVEDP was lower in group C than in group B (P<0.05), whereas peak±dp/dt was higher in group C than in group B (P<0.05) at the same stage. Compared to group A, the cTnT of the remaining two groups increased, respectively (P<0.01), and peaked at 30 minutes. cTnT was less elevated in group C than in group B (P<0.05) during the same period. In groups B and C, myocardial injury was seen under a light microscope, but the injury in group C was lighter than that in group B. CONCLUSION: Methylnorepinephrine can lessen myocardial dysfunction after CPR.

[Nutrient balance and mechanism of biological degradation of oil].

This paper studied the nutrient balance and mechanism for enhancing the bioremediation of petroleum contaminated soils by the bio-slurry method. Oil degrading strains isolated and screened from Liaohe oil field was used. The results show that the suitable weight ratio of N and P element in the nutrient is 5.67:1, which is similar to their proportion in the microbial cells. It was found that the degradation of oil was significantly enhanced by adding nutriment and about 30% oil was decreased in the 14,000 mg/kg-15,000 mg/kg samples during 16 days. Using (NH4)2SO4, NH4NO3, NaNO3, CO(NH2)2 as the nitrogen source respectively, it shows that the inorganic nitrogen is better than the organic one, and the nitrogen in nitrate is more effective than that in ammonia. Adding nutrient salt can change the system's pH and promote the growing of the microbes.