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The purpose of this study was to investigate the association between pregnancy-specific anxiety and elective cesarean section, and identify the critical period in which pregnancy-specific anxiety will affect the elective cesarean section. Primiparous women in the 1st trimester of pregnancy were invited to participate in the cohort. General information on maternal socio-demographic characteristics and environmental exposure were collected using questionnaires. Pregnancy-specific anxiety was assessed by using pregnancy-specific anxiety questionnaire in the 1st, 2nd and 3rd trimester, respectively. Delivery modes and pregnancy complications were abstracted from medical notes. Structural equation modeling (SEM) was adopted to examine the relationship between pregnancy-specific anxiety and elective cesarean section. Results indicated the overall elective cesarean section rate in this study was 45%. Among 1 874 pregnant women, 30.9% women experienced anxiety at least once during pregnancy, and 6.9% women suffered from anxiety in all three trimesters. Anxiety in the 2nd trimester was a significant predictor for elective cesarean section. Young maternal age and low educational level had indirect effects on women’s choice of elective caesarean section through affecting pregnancy-specific anxiety. More attention should be paid to maternal psychological problems, and professional counseling needs to be strengthened to protect women from pregnancy-specific anxiety. [ABSTRACT FROM AUTHOR]

The adsorption of volatile organic compounds by building materials reduces the pollutant concentrations in indoor air. We collected three interior building materials with adsorption potentials—latex paint, micro-carbonized plywood, and moisture-buffering siding—used the sorptive building materials test (SBMT) to determine how much they reduced indoor formaldehyde (HCHO) concentrations, and then assessed the consequent reduction in human cancer risk from HCHO inhalation. Adsorption of HCHO by building materials significantly improved the effective ventilation efficiency. For example, the equivalent ventilation rate for Celite siding—used for humidity control—was 1.44 m3/(m2·h) at 25°C, 50% relative humidity (RH); the loading factor (L) was 0.4 m2/m3, and the HCHO concentration was 0.2 ppm; this effect is equivalent to a higher ventilation rate of approximately 0.6 air changes per hour in a typical Taiwanese dwelling. There was also a substantial reduction of risk in Case MCP-2 (Cin,te: 245 μg/m3, 30°C, 50% RH): males: down 5.73 × 10−4; females: down 4.84 × 10−4). The selection of adsorptive building materials for interior surfaces, therefore, significantly reduces human inhalation of HCHO. Our findings should encourage developing and using innovative building materials that help improve indoor air quality and thus provide building occupants with healthier working and living environments. [ABSTRACT FROM AUTHOR]

Lung ischemia reperfusion injury (LIRI) is one of important complications following lung transplant and cardiopulmonary bypass. Although patients on hemodialysis are still excluded as lung transplant donors because of the possible effects of renal failure on the lungs, increased organ demand has led us to evaluate the influence of chronic kidney disease (CKD) on LIRI. A CKD model was induced by feeding Sprague-Dawley rats an adenine-rich (0.75%) diet for 2, 4 and 6 weeks, and an isolated rat lung in situ model was used to evaluate ischemia reperfusion (IR)-induced acute lung injury. The clinicopathological parameters of LIRI, including pulmonary edema, lipid peroxidation, histopathological changes, immunohistochemistry changes, chemokine CXCL1, inducible nitric oxide synthase (iNOS), proinflammatory and anti-inflammatory cytokines, heat shock protein expression, and nuclear factor-κB (NF-κB) activation were determined. Our results indicated that adenine-fed rats developed CKD as characterized by increased blood urea nitrogen and creatinine levels and the deposition of crystals in the renal tubules and interstitium. IR induced a significant increase in the pulmonary arterial pressure, lung edema, lung injury scores, the expression of CXCL1 mRNA, iNOS level, and protein concentration of the bronchial alveolar lavage fluid (BALF). The tumor necrosis factor-α levels in the BALF and perfusate; the interleukin-10 level in the perfusate; and the malondialdehyde levels in the lung tissue and perfusate were also significantly increased by LIRI. Counterintuitively, adenine-induced CKD significantly attenuated the severity of lung injury induced by IR. CKD rats exhibited increased heat shock protein 70 expression and decreased activation of NF-κB signaling. In conclusion, adenine-induced CKD attenuated LIRI by inhibiting the NF-κB pathway. [ABSTRACT FROM AUTHOR]

The dynamics of BBB permeability after AIS in humans are not well understood. In the present study we measured the evolution of BBB permeability after AIS in humans using MRI. Patients presenting to our institution with a diagnosis of AIS underwent a single dynamic contrast-enhanced MRI (DCE-MRI) sequence to measure BBB permeability during their initial workup. Forty-two patients were included in the final analysis. The patient sample underwent DCE-MRI at a mean time of 23.8hrs after the onset of AIS symptoms (range: 1.3–90.7hrs). At all time-points the BBB permeability within the infarct region of the brain as defined on DWI/ADC was higher compared to the homologous region of the contralateral hemisphere (p<0.005). BBB permeability, expressed as a ratio of infarct permeability to contralateral permeability, was greatest at 6-48hrs after the onset of AIS. Although the data was not acquired longitudinally, these findings suggest that the permeability of the BBB is continually elevated following AIS, which contradicts previous assertions that BBB permeability after AIS follows a biphasic course. Knowledge of BBB dynamics following AIS may provide insight into future treatments for AIS, especially BBB stabilizing agents. [ABSTRACT FROM AUTHOR]

Background: Hospice care has been proved to result in changes to the medical behaviors of terminally ill patients. The aim of this study was to evaluate the effects and medical behavior changes of hospice-shared care intervention among terminally ill gastric cancer patients. Methods: A total of 174 patients who died of gastric cancer between 2012 and 2014 were identified. These patients were divided into two groups: a hospice-shared care group (n = 93) and a control group (n = 81). Results: Among the 174 patients, 84% had advanced stage (stage III or stage IV) cancer. The females and the patients cared by medical oncologists had a higher percentage of hospice-shared care than the males (71% vs 44%, p = 0.001) and those cared by other physicians (63% vs 41%, p = 0.004). Compared to the control group, the hospice-shared care group underwent lower incidence of life sustaining or aggressive medical treatments, including intensive care unit admission (2% vs 26%, p<0.001), intubation (1% vs 27%, p<0.001), cardiopulmonary-cerebral resuscitation (0% vs 11%, p = 0.001), ventilator use (1% vs 27%, p<0.001), inotropic agent use (8% vs 46%, p<0.001), total or partial parenteral nutrition use (38% vs. 58%, p = 0.029), and blood transfusion (45% vs 74%, p<0.001). Besides, the hospice-shared care group had a higher percentage of palliative treatments than the control group, including signed Do-Not-Resuscitate (DNR) orders (95% vs 37%, p<0.001), receiving home hospice care (16% vs 1%, p<0.001), and indicating home as the realistically preferred place of death (41% vs 19%, p = 0.001). The hospice ward admission rate in the hospice-shared care group increased from 30% to 53% from 2012 to 2014. Conclusion: The use of hospice-shared care for gastric cancer patients could increase the rate of signed DNR orders, decrease the use of life sustaining and aggressive/palliative treatments, and improve quality of life. [ABSTRACT FROM AUTHOR]

Ecosystem light use efficiency (LUE) is a key factor of production models for gross primary production (GPP) predictions. Previous studies revealed that ecosystem LUE could be significantly enhanced by an increase on diffuse radiation. Under large spatial heterogeneity and increasing annual diffuse radiation in China, eddy covariance flux data at 6 sites across different ecosystems from 2003 to 2007 were used to investigate the impacts of diffuse radiation indicated by the cloudiness index (CI) on ecosystem LUE in grassland and forest ecosystems. Our results showed that the ecosystem LUE at the six sites was significantly correlated with the cloudiness variation (0.24≤R2≤0.85), especially at the Changbaishan temperate forest ecosystem (R2 = 0.85). Meanwhile, the CI values appeared more frequently between 0.8 and 1.0 in two subtropical forest ecosystems (Qianyanzhou and Dinghushan) and were much larger than those in temperate ecosystems. Besides, cloudiness thresholds which were favorable for enhancing ecosystem carbon sequestration existed at the three forest sites, respectively. Our research confirmed that the ecosystem LUE at the six sites in China was positively responsive to the diffuse radiation, and the cloudiness index could be used as an environmental regulator for LUE modeling in regional GPP prediction. [ABSTRACT FROM AUTHOR]

The transcription factor Sp1 is implicated in the activation of G0/G1 phase genes. Modulation of Sp1 transcription activities may affect G1-S checkpoint, resulting in changes in cell proliferation. In this study, our results demonstrated that activated poly(ADP-ribose) polymerase 1 (PARP-1) promoted cell proliferation by inhibiting Sp1 signaling pathway. Cell proliferation and cell cycle assays demonstrated that PARP inhibitors or PARP-1 siRNA treatment significantly inhibited proliferation of hepatoma cells and induced G0/G1 cell cycle arrest in hepatoma cells, while overexpression of PARP-1 or PARP-1 activator treatment promoted cell cycle progression. Simultaneously, inhibition of PARP-1 enhanced the expression of Sp1-mediated checkpoint proteins, such as p21 and p27. In this study, we also showed that Sp1 was poly(ADP-ribosyl)ated by PARP-1 in hepatoma cells. Poly(ADP-ribosyl)ation suppressed Sp1 mediated transcription through preventing Sp1 binding to the Sp1 response element present in the promoters of target genes. Taken together, these data indicated that PARP-1 inhibition attenuated the poly(ADP-ribosyl)ation of Sp1 and significantly increased the expression of Sp1 target genes, resulting in G0/G1 cell cycle arrest and the decreased proliferative ability of the hepatoma cells. [ABSTRACT FROM AUTHOR]

Objective: To examine the prevalence of snoring during pregnancy and its effects on key pregnancy outcomes. Methods: Pregnant women were consecutively recruited in their first trimester. Habitual snoring was screened by using a questionnaire in the 1st and 3rd trimester, respectively. According to the time of snoring, participants were divided into pregnancy onset snorers, chronic snorers and non-snorers. Logistic regressions were performed to examine the associations between snoring and pregnancy outcomes. Results: Of 3 079 pregnant women, 16.6% were habitual snorers, with 11.7% were pregnancy onset snorers and 4.9% were chronic snorers. After adjusting for potential confounders, chronic snorers were independently associated with gestational diabetes mellitus (GDM) (RR 1.66, 95%CI 1.09–2.53). Both pregnancy onset and chronic snorers were independently associated with placental adhesion (RR 1.96, 95%CI 1.17–3.27, and RR 2.33, 95%CI 1.22–4.46, respectively). Pregnancy onset snorers were at higher risk of caesarean delivery (RR 1.37, 95%CI 1.09–1.73) and having macrosomia (RR 1.54, 95%CI 1.05–2.27) and large for gestational age (LGA) (RR 1.71, 95%CI 1.31–2.24) infants. In addition, being overweight or obese before pregnancy plays an important role in mediating snoring and adverse pregnancy outcomes. Conclusions: Maternal snoring may increase the risk of adverse pregnancy outcomes, and being overweight or obese before pregnancy with snoring is remarkable for researchers. Further studies are still needed to confirm our results. [ABSTRACT FROM AUTHOR]

When a long distance oil pipeline crosses an earthquake disaster area, inertial force and strong ground motion can cause the pipeline stress to exceed the failure limit, resulting in bending and deformation failure. To date, researchers have performed limited safety analyses of oil pipelines in earthquake disaster areas that include stress analysis. Therefore, using the spectrum method and theory of one-dimensional beam units, CAESAR II is used to perform a dynamic earthquake analysis for an oil pipeline in the XX earthquake disaster area. This software is used to determine if the displacement and stress of the pipeline meet the standards when subjected to a strong earthquake. After performing the numerical analysis, the primary seismic action axial, longitudinal and horizontal displacement directions and the critical section of the pipeline can be located. Feasible project enhancement suggestions based on the analysis results are proposed. The designer is able to utilize this stress analysis method to perform an ultimate design for an oil pipeline in earthquake disaster areas; therefore, improving the safe operation of the pipeline. [ABSTRACT FROM AUTHOR]

53BP1 regulates DNA double-strand break (DSB) repair. In functional assays for specific DSB repair pathways, we found that 53BP1 was important in the conservative non-homologous end-joining (C-NHEJ) pathway, and this activity was dependent upon RNF8 and RNF168. We observed that 53BP1 protein was diffusely abundant in nuclei, and upon ionizing radiation, 53BP1 was everywhere degraded except at DNA damage sites. Depletion of RNF8 or RNF168 blocked the degradation of the diffusely localized nuclear 53BP1, and ionizing radiation induced foci (IRIF) did not form. Furthermore, when 53BP1 degradation was inhibited, a subset of 53BP1 was bound to DNA damage sites but bulk, unbound 53BP1 remained in the nucleoplasm, and localization of its downstream effector RIF1 at DSBs was abolished. Our data suggest a novel mechanism for responding to DSB that upon ionizing radiation, 53BP1 was divided into two populations, ensuring functional DSB repair: damage site-bound 53BP1 whose binding signal is known to be generated by RNF8 and RNF168; and unbound bulk 53BP1 whose ensuing degradation is regulated by RNF8 and RNF168. [ABSTRACT FROM AUTHOR]

Background: Axl is a cell surface receptor tyrosine kinase, and activation of the Axl attenuates inflammation induced by various stimuli. Growth arrest-specific 6 (Gas6) has high affinity for Axl receptor. The role of Gas6/Axl signaling in ischemia-reperfusion-induced acute lung injury (IR-ALI) has not been explored previously. We hypothesized that Gas6/Axl signaling regulates IR-induced alveolar inflammation via a pathway mediated by suppressor of cytokine signaling 3 (SOCS3). Methods: IR-ALI was induced by producing 30 min of ischemia followed by 90 min of reperfusion in situ in an isolated and perfused rat lung model. The rats were randomly allotted to a control group and IR groups, which were treated with three different doses of Gas6. Mouse alveolar epithelium MLE-12 cells were cultured in control and hypoxia-reoxygenation (HR) conditions with or without Gas6 and Axl inhibitor R428 pretreatment. Results: We found that Gas6 attenuated IR-induced lung edema, the production of proinflammatory cytokines in perfusates, and the severity of ALI ex vivo. IR down-regulated SOCS3 expression and up-regulated NF-κB, and Gas6 restored this process. In the model of MLE-12 cells with HR, Gas6 suppressed the activation of TRAF6 and NF-κB by up-regulating SOCS3. Axl expression of alveolar epithelium was suppressed in IR-ALI but Gas6 restored phosphorylation of Axl. The anti-inflammatory effect of Gas6 was antagonized by R428, which highlighted that phosphorylation of Axl mediated the protective role of Gas6 in IR-ALI. Conclusions: Gas6 up-regulates phosphorylation of Axl on alveolar epithelium in IR-ALI. The Gas6/Axl signaling activates the SOCS3-mediated pathway and attenuates IR-related inflammation and injury. [ABSTRACT FROM AUTHOR]

Ischemia-reperfusion (IR)-induced acute lung injury (ALI) is implicated in several clinical conditions including lung transplantation, cardiopulmonary bypass surgery, re-expansion of collapsed lung from pneumothorax or pleural effusion and etc. IR-induced ALI remains a challenge in the current treatment. Carbonic anhydrase has important physiological function and influences on transport of CO2. Some investigators suggest that CO2 influences lung injury. Therefore, carbonic anhydrase should have the role in ALI. This study was undertaken to define the effect of a carbonic anhydrase inhibitor, acetazolamide (AZA), in IR-induced ALI, that was conducted in a rat model of isolated-perfused lung with 30 minutes of ischemia and 90 minutes of reperfusion. The animals were divided into six groups (n = 6 per group): sham, sham + AZA 200 mg/kg body weight (BW), IR, IR + AZA 100 mg/kg BW, IR + AZA 200 mg/kg BW and IR+ AZA 400 mg/kg BW. IR caused significant pulmonary micro-vascular hyper-permeability, pulmonary edema, pulmonary hypertension, neutrophilic sequestration, and an increase in the expression of pro-inflammatory cytokines. Increases in carbonic anhydrase expression and perfusate pCO2 levels were noted, while decreased Na-K-ATPase expression was noted after IR. Administration of 200mg/kg BW and 400mg/kg BW AZA significantly suppressed the expression of pro-inflammatory cytokines (TNF-α, IL-1, IL-6 and IL-17) and attenuated IR-induced lung injury, represented by decreases in pulmonary hyper-permeability, pulmonary edema, pulmonary hypertension and neutrophilic sequestration. AZA attenuated IR-induced lung injury, associated with decreases in carbonic anhydrase expression and pCO2 levels, as well as restoration of Na-K-ATPase expression. [ABSTRACT FROM AUTHOR]

Obesity in humans and mice is typified by an activated macrophage phenotype in the visceral adipose tissue (VAT) leading to increased macrophage-mediated inflammation. microRNAs (miRNAs) play an important role in regulating inflammatory pathways in macrophages, and in this study we compared miRNA expression in the VAT of insulin resistant morbidly obese humans to a non-obese cohort with normal glucose tolerance. miR-223-3p was found to be significantly upregulated in the whole omental tissue RNA of 12 human subjects, as were 8 additional miRNAs. We then confirmed that miR-223 upregulation was specific to the stromal vascular cells of human VAT, and found that miR-223 levels were unchanged in adipocytes and circulating monocytes of the non-obese and obese. miR-223 ablation increased basal / unstimulated TLR4 and STAT3 expression and LPS-stimulated TLR4, STAT3, and NOS2 expression in primary macrophages. Conversely, miR-223 mimics decreased TLR4 expression in primary macrophage, at the same time it negatively regulated FBXW7 expression, a well described suppressor of Toll-like receptor 4 (TLR4) signaling. We concluded that the abundance of miR-223 in macrophages significantly modulates macrophage phenotype / activation state and response to stimuli via effects on the TLR4/FBXW7 axis. [ABSTRACT FROM AUTHOR]

Ischemia-reperfusion (IR)-induced acute lung injury (ALI) is implicated in several clinical conditions like lung transplantation, acute pulmonary embolism after thrombolytic therapy, re-expansion of collapsed lung from pneumothorax or pleural effusion, cardiopulmonary bypass and etc. Because mortality remains high despite advanced medical care, prevention and treatment are important clinical issues for IR-induced ALI. Vascular endothelial growth factor (VEGF) has a controversial role in ALI. We therefore conducted this study to determine the effects of anti-VEGF antibody in IR-induced ALI. In the current study, the IR-induced ALI was conducted in a rat model of isolated-perfused lung in situ in the chest. The animals were divided into the control, control + preconditioning anti-VEGF antibody (bevacizumab, 5mg/kg), IR, IR + preconditioning anti-VEGF antibody (1mg/kg), IR+ preconditioning anti-VEGF antibody (5mg/kg) and IR+ post-IR anti-VEGF antibody (5mg/kg) group. There were eight adult male Sprague-Dawley rats in each group. The IR caused significant pulmonary micro-vascular hyper-permeability, pulmonary edema, neutrophilic infiltration in lung tissues, increased tumor necrosis factor-α, and total protein concentrations in bronchoalveolar lavage fluid. VEGF and extracellular signal-regulated kinase (ERK) were increased in IR-induced ALI. Administration of preconditioning anti-VEGF antibody significantly suppressed the VEGF and ERK expressions and attenuated the IR-induced lung injury. This study demonstrates the important role of VEGF in early IR-induced ALI. The beneficial effects of preconditioning anti-VEGF antibody in IR-induced ALI include the attenuation of lung injury, pro-inflammatory cytokines, and neutrophilic infiltration into the lung tissues. [ABSTRACT FROM AUTHOR]

Co-expression analysis has been employed to predict gene function, identify functional modules, and determine tumor subtypes. Previous co-expression analysis was mainly conducted at bulk tissue level. It is unclear whether co-expression analysis at the single-cell level will provide novel insights into transcriptional regulation. Here we developed a computational approach to compare glioblastoma expression profiles at the single-cell level with those obtained from bulk tumors. We found that the co-expressed genes observed in single cells and bulk tumors have little overlap and show distinct characteristics. The co-expressed genes identified in bulk tumors tend to have similar biological functions, and are enriched for intrachromosomal interactions with synchronized promoter activity. In contrast, single-cell co-expressed genes are enriched for known protein-protein interactions, and are regulated through interchromosomal interactions. Moreover, gene members of some protein complexes are co-expressed only at the bulk level, while those of other complexes are co-expressed at both single-cell and bulk levels. Finally, we identified a set of co-expressed genes that can predict the survival of glioblastoma patients. Our study highlights that comparative analyses of single-cell and bulk gene expression profiles enable us to identify functional modules that are regulated at different levels and hold great translational potential. [ABSTRACT FROM AUTHOR]

Objective: To explore the relationship between TβRII [type II TGFβ (transforming growth factor β) receptor] expression and clinicopathological characteristics, and to evaluate the prognostic significance of TβRII expression in breast cancer. Methods: Clinicopathological data and prognostic information of 108 patients with histologically confirmed breast cancer who were surgically treated at China Medical University between January 2007 and September 2008 were reviewed and the association between the clinicopathological characteristics and TβRII expression was analyzed by chi-square test and multivariate analysis. The expression of TβRII was assessed by immunohistochemistry. Results: Of the 108 patients, 60 cases were TβRII positive and 48 cases were negative. There was no significant association between TβRII expression of the patients older than 40 years and that of the younger than 40 years (56.0% vs 50.0%; P = 0.742). The TβRII expression rate was significantly increased in patients with lymph node metastasis compared to those without lymph node metastasis (67.40% vs 46.8%; P = 0.033). Statistically significant relationships were found between increasing tumor clinical stage and high TβRII expression (P = 0.011). TβRII expression was not associated with the expression of ER(estrogen receptor)、PR, (progesterone receptor)、Her-2 (human epidermal growth factor receptor 2) (P = 0.925,P = 0.861, and P = 0.840, respectively). Patients with high TβRII expression showed poorer 5-year disease-free survival (DFS) compared to those with low expression (66.7% vs 45.6%; P = 0.028) by univariate analysis. Survival analysis demonstrated that TβRII was associated with poor DFS (P = 0.011). Subgroup analysis revealed that TβRII expression was associated with shorter DFS in patients with lymph node metastasis, ER-positive, PR-positive or Her-2-negative tumors (P = 0.006, P = 0.016, P = 0.022, and P = 0.033, respectively). Cox regression analysis revealed that high TβRII expression was related to poor 5-year DFS, and it was an independent factor for predicting the poor outcome for breast cancer patients (P = 0.016). Conclusions: High levels of TβRII expression were associated with lymph node metastasis, increasing tumor clinical stage, and poorer 5-year DFS in patients with breast cancer. TβRII may be a potential prognostic marker for breast cancer. [ABSTRACT FROM AUTHOR]

Improving the separation efficiency of the inclined oil/water separator, a new type of gravity separation equipment, is of great importance. In order to obtain a comprehensive understanding of the internal flow field of the separation process of oil and water within this separator, a numerical simulation based on Euler multiphase flow analysis and the realizable k-ε two equation turbulence model was executed using Fluent software. The optimal value ranges of the separator’s various structural parameters used in the numerical simulation were selected through orthogonal array experiments. A field experiment on the separator was conducted with optimized structural parameters in order to validate the reliability of the numerical simulation results. The research results indicated that the horizontal position of the dispenser, the hole number, and the diameter had significant effects on the oil/water separation efficiency, and that the longitudinal position of the dispenser and the position of the weir plate had insignificant effects on the oil/water separation efficiency. The optimal structural parameters obtained through the orthogonal array experiments resulted in an oil/water separation efficiency of up to 95%, which was 4.996% greater than that realized by the original structural parameters. [ABSTRACT FROM AUTHOR]

Ventilator-induced lung injury is associated with inflammatory mechanism and causes high mortality. The objective of this study was to discover the role of IL-33 and its ST2 receptor in acute lung injury induced by mechanical ventilator (ventilator-induced lung injury; VILI). Male Wistar rats were intubated after tracheostomy and received ventilation at 10 cm H2O of inspiratory pressure (PC10) by a G5 ventilator for 4 hours. The hemodynamic and respiratory parameters were collected and analyzed. The morphological changes of lung injury were also assessed by histological H&E stain. The dynamic changes of lung injury markers such as TNF-α and IL-1β were measured in serum, bronchoalveolar lavage fluid (BALF), and lung tissue homogenization by ELISA assay. During VILI, the IL-33 profile change was detected in BALF, peripheral serum, and lung tissue by ELISA analysis. The Il-33 and ST2 expression were analyzed by immunohistochemistry staining and western blot analysis. The consequence of VILI by H&E stain showed inducing lung congestion and increasing the expression of pro-inflammatory cytokines such as TNF-α and IL-1β in the lung tissue homogenization, serum, and BALF, respectively. In addition, rats with VILI also exhibited high expression of IL-33 in lung tissues. Interestingly, the data showed that ST2L (membrane form) was highly accumulated in the membrane fraction of lung tissue in the PC10 group, but the ST2L in cytosol was dramatically decreased in the PC10 group. Conversely, the sST2 (soluble form) was slightly decreased both in the membrane and cytosol fractions in the PC10 group compared to the control group. In conclusion, these results demonstrated that ST2L translocation from the cytosol to the cell membranes of lung tissue and the down-expression of sST2 in both fractions can function as new biomarkers of VILI. Moreover, IL-33/ST2 signaling activated by mechanically responsive lung injury may potentially serve as a new therapy target. [ABSTRACT FROM AUTHOR]

Peripheral blood mononuclear cells (PBMCs), including rare circulating stem and progenitor cells (CSPCs), have important yet poorly understood roles in the maintenance and repair of blood vessels and perfused organs. Our hypothesis was that the identities and functions of CSPCs in cardiovascular health could be ascertained by analyzing the patterns of their co-expressed markers in unselected PBMC samples. Because gene microarrays had failed to detect many stem cell-associated genes, we performed quantitative real-time PCR to measure the expression of 45 primitive and tissue differentiation markers in PBMCs from healthy and hypertensive human subjects. We compared these expression levels to the subjects' demographic and cardiovascular risk factors, including vascular stiffness. The tested marker genes were expressed in all of samples and organized in hierarchical transcriptional network modules, constructed by a bottom-up approach. An index of gene expression in one of these modules (metagene), defined as the average standardized relative copy numbers of 15 pluripotency and cardiovascular differentiation markers, was negatively correlated (all p<0.03) with age (R2 = −0.23), vascular stiffness (R2 = −0.24), and central aortic pressure (R2 = −0.19) and positively correlated with body mass index (R2 = 0.72, in women). The co-expression of three neovascular markers was validated at the single-cell level using mRNA in situ hybridization and immunocytochemistry. The overall gene expression in this cardiovascular module was reduced by 72±22% in the patients compared with controls. However, the compactness of both modules was increased in the patients' samples, which was reflected in reduced dispersion of their nodes' degrees of connectivity, suggesting a more primitive character of the patients' CSPCs. In conclusion, our results show that the relationship between CSPCs and vascular function is encoded in modules of the PBMCs transcriptional network. Furthermore, the coordinated gene expression in these modules can be linked to cardiovascular risk factors and subclinical cardiovascular disease; thus, this measure may be useful for their diagnosis and prognosis. [ABSTRACT FROM AUTHOR]

Hypercapnic acidosis (HCA) has protective effects in animal models of acute lung injury, but the mechanism underlying the effect of HCA is unclear. Heme oxygenase-1 (HO-1) is an antioxidant enzyme that protects tissue from inflammation injury. We investigated whether HO-1 contributes to the protective effects of HCA in ischemia-reperfusion (IR)-induced lung injury. Typical acute lung injury in rats was successfully induced by 40 min of ischemia and 90 min of reperfusion in an isolated perfused lung model. The rat lungs were randomly assigned to the control group, IR group or IR + HCA group with or without zinc protoporphyrin IX (ZnPP), an HO-1 activity inhibitor. At the end of the experiment, bronchoalveolar lavage fluid (BALF) and lung tissues were collected to evaluate the degree of lung injury. In in vitro experiments, HO-1 siRNA transfected A549 cells were exposed to a normoxic or hypoxia-reoxygenation (H/R) environment in the presence or absence of HCA. IR caused significant increases in the pulmonary arterial pressure, lung weight to body weight and wet/dry ratios, lung weight gain, capillary filtration coefficient, lung injury scores, neutrophil infiltration, and concentrations of protein and TNF-α in the BALF. IR also induced degradation of inhibitor of nuclear factor (NF)-κB-α, increased IκB kinase (IKK)-β phosphorylation and nuclear translocation of NF-κB, and up-regulated HO-1 expression and activity. Furthermore, IR decreased Bcl-2 protein expression and increased the number of active caspase-3 stained cells. HCA treatment enhanced HO-1 expression and activity, and accordingly reduced IKK-NF-κB signaling, inhibited apoptosis, and significantly attenuated IR-induced changes. Treatment with ZnPP partially blocked the protective effect of HCA. In addition, HO-1 siRNA significantly reversed HCA-mediated inhibition of NF-κB signaling in A549 cells subjected to H/R. In conclusion, the protective effect of HCA in IR lung injury in rats was mediated in part by the anti-inflammatory and anti-apoptotic action of HO-1. [ABSTRACT FROM AUTHOR]