IL-17A-producing T cells exacerbate fine particulate matter-induced lung inflammation and fibrosis by inhibiting PI3K/Akt/mTOR-mediated autophagy.

Fine particulate matter (PM2.5) is the primary air pollutant that is able to induce airway injury. Compelling evidence has shown the involvement of IL-17A in lung injury, while its contribution to PM2.5-induced lung injury remains largely unknown. Here, we probed into the possible role of IL-17A in mouse models of PM2.5-induced lung injury. Mice were instilled with PM2.5 to construct a lung injury model. Flow cytometry was carried out to isolate γδT and Th17 cells. ELISA was adopted to detect the expression of inflammatory factors in the supernatant of lavage fluid. Primary bronchial epithelial cells (mBECs) were extracted, and the expression of TGF signalling pathway-, autophagy- and PI3K/Akt/mTOR signalling pathway-related proteins in mBECs was detected by immunofluorescence assay and Western blot analysis. The mitochondrial function was also evaluated. PM2.5 aggravated the inflammatory response through enhancing the secretion of IL-17A by γδT/Th17 cells. Meanwhile, PM2.5 activated the TGF signalling pathway and induced EMT progression in bronchial epithelial cells, thereby contributing to pulmonary fibrosis. Besides, PM2.5 suppressed autophagy of bronchial epithelial cells by up-regulating IL-17A, which in turn activated the PI3K/Akt/mTOR signalling pathway. Furthermore, IL-17A impaired the energy metabolism of airway epithelial cells in the PM2.5-induced models. This study suggested that PM2.5 could inhibit autophagy of bronchial epithelial cells and promote pulmonary inflammation and fibrosis by inducing the secretion of IL-17A in γδT and Th17 cells and regulating the PI3K/Akt/mTOR signalling pathway.

Upregulation of Klotho potentially inhibits pulmonary vascular remodeling by blocking the activation of the Wnt signaling pathway in rats with PM2.5-induced pulmonary arterial hypertension.

We evaluated the effects of Klotho on pulmonary vascular remodeling and cell proliferation and apoptosis in rat models with PM2.5-induced pulmonary arterial hypertension (PAH) via the Wnt signaling pathway. After establishing rat models of PM2.5-induced PAH, these Sprague-Dawley male rats were randomized into control and model groups. Cells extracted from the model rats were sub-categorized into different groups. Activation of Wnt/ß-catenin signaling transcription factor was detected by a TOPFlash/FOPFlash assay. A serial of experiment was conducted to identify the mechanism of Klotho on PHA via the Wnt signaling pathway. VEGF levels and PaCO2 content were higher in the model group, while PaO2, NO2- /NO3- content and Klotho level was lower compared to the control group. In comparison to the control group, the model group had decreased Klotho and Bax levels, and elevated Wnt-1, ß-catenin, bcl-2, survivin, and PCNA expression, VEGF, IL-6, TNF-α, TNF-ß1, and bFGF levels, as well as the percentage of pulmonary artery ring contraction. The Klotho vector, DKK-1 and DKK-1 + Klotho vector groups exhibited reduced cell proliferation, luciferase activity, and the expression of Wnt-1, ß-catenin, bcl-2, survivin, and PCNA, as well as shortened S phase compared with the blank and NC groups. Compared with the Klotho vector and DKK-1 groups, the DKK-1 + Klotho vector groups had reduced cell proliferation, luciferase activity, and the expression of Wnt-1, ß-catenin, bcl-2, survivin, and PCNA, as well as a shortened S phase. Conclusively, Klotho inhibits pulmonary vascular remodeling by inactivation of Wnt signaling pathway.

miR-143 suppresses the proliferation of NSCLC cells by inhibiting the epidermal growth factor receptor.

MicroRNAs (miRs) regulate the proliferation and metastasis of numerous cancer cell types. It was previously reported that miR-143 levels were downregulated in non-small cell lung cancer (NSCLC) tissues and cell lines, and that the migration and invasion of NSCLC cells was inhibited upon suppression of cell proliferation and colony formation by the upregulation of miR-143. Epidermal growth factor receptor (EGFR), which is a vital factor in the promotion of cancer cell proliferation and has been investigated as a potential focus in cancer therapy, has been reported to be a possible target of miR-143. The present study aimed to investigate the role of miR-143 in NSCLC using NSCLC cell lines and primary cells from NSCLC patients. NSCLC cells were co-transfected with EGFR and miR-143, and the mRNA and protein expression of EGFR were analyzed. Furthermore, the activity of the transfected cancer cells with regard to colony formation, migration, invasion and apoptosis were evaluated. The levels of miR-143 were decreased in the NSCLC cell lines and primary cells from patients with NSCLC compared with the controls. Following transfection with miR-143, the ability of NSCLC cells to proliferate, form colonies, migrate and invade was inhibited. Similarly, knockdown of EGFR led to the suppression of NSCLC cell proliferation. The mRNA and protein expression levels of EGFR were significantly reduced following miR-143 overexpression, and the level of miR-143 was inversely correlated with that of EGFR in NSCLC cells. The results of the present study demonstrated that miR-143 was able to suppress NSCLC cell proliferation and invasion by inhibiting the effects of EGFR, suggesting that EGFR may be considered a potential target for NSCLC therapy.

Clinical evaluation compared to the pulse indicator continuous cardiac output system in the hemodynamic assessment of critically ill patients.

OBJECTIVE: The objective was to assess the effects of pulse indicator continuous cardiac output catheterization on the management of critically ill patients and the alteration of therapy in intensive care units. METHODS: One hundred thirty-two patients with primary physiological abnormalities of hypotension or hypoxemia were evaluated. Prior to catheterization, physicians were asked to complete a questionnaire that collected information regarding predictions of the ranges of several hemodynamic variables and plans for therapy. After catheterization, each chart was reviewed by a panel of intensive care attending physicians to determine the possibility of altering the therapy. RESULTS: Overall correct classification of the key variables ranged from 46.0% to 65.4%. Catheterization results prompted alterations in therapy for 45.5% of patients. The fellows were less accurate in predicting hemodynamic values for patients whose diagnoses were unknown, and the primary abnormality was hypotension. There was significant difference in the physicians' abilities to predict the hemodynamics for the subgroups with and without acute myocardial infarction. When the patients were divided into 3 subgroups by Acute Physiology and Chronic Health Evaluation II and Sepsis-related Organ Failure Assessment scores, the fellows had the most difficulty predicting the variables of the moderately ill patients in the middle subgroup, which led to the greatest percentage of therapy alterations for this subgroup; and this difference was significant. CONCLUSIONS: The hemodynamic variables obtained from pulse indicator continuous cardiac output catheterization improved the accuracy of bedside evaluations and led to alterations in therapeutic plans, particularly among the moderately ill patients with hypotension or unknown diagnoses.

Effects of chest compressions on cardiorespiratory function in a non-arrested porcine model.

BACKGROUND: The effects of chest compressions to hemodynamic and respiratory parameters during hands-only cardiopulmonary resuscitation (CPR) in a non-arrested patient who suddenly collapses are confusing. In this research, we investigated the effects of chest compressions in a non-arrested porcine model. METHODS: Fourteen male domestic pigs were randomized into sham control group (SHAM group, only anesthetized and instrumented without chest compression, n = 6) or chest compression group (CC group, 2 minutes of chest compressions, n = 8). Continuous hemodynamic parameters, dynamic lung compliance (Cdyn), and blood gas analysis outcomes were recorded. Serum levels of catecholamine were measured at baseline and 2 minutes, 30 minutes, 4 hours, and 24 hours after chest compressions. Chest computed tomography (CT) was performed at 30 minutes and 24 hours. Conventional histopathology evaluation was performed. RESULTS: After two minutes of chest compressions in the CC group, heart rate and extravascular lung water increased significantly; mean arterial pressure, stroke volume, and global ejection fraction significantly decreased. Cdyn significantly decreased to valley levels at 30 minutes and slowly recovered. Compared with the baseline, serum levels of catecholamine significantly increased at 2 minutes and rapidly decreased 24 hours later. At 30 minutes after chest compressions, chest CT showed local exudation, which was absorbed 24 hours later. CONCLUSIONS: This research showed that 2 minutes of chest compressions causes various heart and lung tissue damage in the normal a normal porcine model. It also impacts the hemodynamic and Cdyn.

Shen-fu injection attenuates postresuscitation myocardial dysfunction in a porcine model of cardiac arrest.

To investigate the effect of Shen-Fu injection (SFI) for the management of postresuscitation myocardial dysfunction in a porcine model of cardiac arrest. Ventricular fibrillation was induced electrically in anesthetized domestic swine. After 4 min of untreated ventricular fibrillation, cardiopulmonary resuscitation was initiated. Sixteen successfully resuscitated pigs were randomized to receive a continuous infusion of either SFI (0.24 mg/min) or saline placebo for 6 h, beginning 15 min after return of spontaneous circulation (ROSC). The SFI treatment produced better left ventricular +dP/dtmax, -dP/dtmax, cardiac output, and ejection fraction after ROSC. The SFI treatment also produced lower serum cardiac troponin I, lactate levels, and left ventricle malondialdehyde content after ROSC, whereas left ventricle superoxide dismutase, Na-K-ATPase, and Ca-ATPase activity were significantly increased in the SFI group when compared with saline group. The cardioprotective effect of SFI was further confirmed by myocardial ultrastructure examination. Shen-Fu injection can attenuate postresuscitation myocardial dysfunction through beneficial effects on energy metabolism and remarkable antioxidant capacity.

Comparison of the efficacy of nifekalant and amiodarone in a porcine model of cardiac arrest.

OBJECTIVE: To compare the efficacy of nifekalant and amiodarone in the treatment of cardiac arrest in a porcine model. METHODS: After 4min of untreated ventricular fibrillation, animals were randomly treated with nifekalant (2mgkg(-1)), amiodarone (5mgkg(-1)) or saline placebo (n=12 pigs per group). Precordial compression and ventilation were initiated after drug administration and defibrillation was attempted 2min later. Hemodynamics were continuously measured for 6h after successful resuscitation. RESULTS: Compared with saline, nifekalant and amiodarone equally decreased the number of electric shocks, defibrillation energy, epinephrine dose, and duration of cardiopulmonary resuscitation required for successful resuscitation (P<0.01). The incidence of restoration of spontaneous circulation (ROSC) and the 24-h survival rate were higher in both antiarrhythmic drug groups (P<0.05) vs. the saline group. Furthermore, post-resuscitation myocardial dysfunction at 4-6h after successful resuscitation was improved in animals given antiarrhythmic drugs as compared with the saline group (P<0.05). There were no differences between nifekalant and amiodarone for any of these parameters. CONCLUSION: The effect of nifekalant was similar to that of amiodarone for improving defibrillation efficacy and for the treatment of cardiac arrest. Administration of either nifekalant or amiodarone before defibrillation increased the ROSC and 24-h survival rates and improved post-resuscitation cardiac function in this porcine model.