Association between plasma adiponectin levels and left ventricular systolic dysfunction in sepsis patients.

PURPOSE: As a well-known cardioprotective factor, the relevance of adiponectin (APN) to heart function following sepsis remains largely unknown. The present study evaluated the effects of plasma APN levels on heart function and 28-day mortality in sepsis patients. MATERIALS AND METHODS: This was a prospective study that was performed with 98 patients with sepsis and 32 controls. Left ventricular systolic dysfunction (LVSD) was defined as a left ventricular ejection fraction (LVEF) ≤ 45% based on echocardiography. The effects of APN on the development of sepsis-related LVSD and prediction of 28-day mortality were evaluated. RESULTS: Plasma APN levels significantly decreased in sepsis patients compared with controls, with rising severity of illness, and positively correlated with the LVEF and stroke volume index. Sepsis patients with LVSD had lower APN levels than patients without LVSD. According to the receiver operating characteristic curve, plasma APN levels had the comparable value in prediction of LVSD incidence than those conditional factors, including brain natriuretic peptide (BNP) and highly sensitive cardiac troponin T (hsTnT). Twenty-three of the 98 sepsis patients (23.47%) died at 28 days. Adiponectin levels were an independent predictive factor for 28-day mortality. CONCLUSIONS: Low APN levels were associated with the incidence of LVSD and 28-day mortality in sepsis patients. Adiponectin may be a novel factor that may be useful for the diagnosis of LVSD.

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.

Dapk1 improves inflammation, oxidative stress and autophagy in LPS-induced acute lung injury via p38MAPK/NF-κB signaling pathway.

OBJECTIVE: To investigate the impact of death-associated protein kinase 1 (Dapk1) on lipopolysaccharide (LPS)-induced acute lung injury (ALI) via p38MAPK/NF-κB pathway. METHODS: Dapk1+/+ and Dapk1-/- mice were randomized into Control, LPS, SB203580 (a p38MAPK pathway inhibitor) + LPS, and PDTC (a NF-κB pathway inhibitor) + LPS groups. Cell counts, lung wet to dry weight ratio (W/D weight ratio), as well as indicators of oxidative stress were determined followed by the detection with HE staining, ELISA, qRT-PCR, Western blotting and Immunofluorescence. Besides, to explore whether the effect of Dapk1 on ALI directly mediated via p38MAPK/NF-κB pathway, mice were injected with TC-DAPK 6 (a Dapk1 inhibitor) with or without SB203580/PDTC before LPS administration. RESULTS: LPS induced lung injury with increased lung W/D weight ratio, which could be partly reversed by SB203580 and PDTC in LPS-induced mice with activated p38MAPK/NF-κB pathway in lung tissues, especially in Dapk1-/- mice. SB203580 and PDTC reduced total cells and neutrophils in BALF in LPS-induced mice, accompanying with decreased levels of TNF-α, IL-6, MPO, LPO and MDA and the expressions of beclin-1, Atg5 and LC3II, but with the up-regulated activities of SOD and GSH-Px, as well as p62 protein expression. Besides, TC-DAPK 6 aggravated the pathologic injury in LPS-induced ALI with more serious inflammatory response, oxidative stress and autophagy as well as the activated p38MAPK/NF-κB pathway, which were reversed by SB203580 or PDTC. CONCLUSION: Dapk1 improved oxidative stress, inhibited autophagy, and reduce inflammatory response of LPS-induced ALI mice by inhibiting p38MAPK/NF-κB pathway.

Aqueous Extract of Whitmania Pigra Whitman Alleviates Thrombus Burden Via Sirtuin 1/NF-κB Pathway.

BACKGROUND: Whitmania pigra Whitman (W pigra), a traditional Chinese medicine, has functions of breaking stagnant and eliminating blood stasis. The aim of this study was to investigate the underlying mechanism of W pigra against deep vein thrombosis (DVT). METHODS: A rat model of DVT induced by inferior vena cava stenosis was successfully established. Rats were administered vehicle (saline solution, p.o.), three doses of W pigra aqueous extract (34.7, 104.2, or 312.5 mg crude W pigra/kg, p.o.), heparin (200 U/kg, i.v.), or clopidogrel (25 mg/kg, p.o.) once daily for 2 d. Thrombus weight and histopathological changes were examined. Blood samples were collected to determine blood cell counts, blood viscosity, blood coagulation, blood fibrinolysis, serum levels of interleukin-1ß, and tumor necrosis factor-α. Protein expressions of Sirtuin1 (SIRT1), acetylated p65 (Ace-p65), and phosphorylated p65 (p-p65) were determined by Western blot. Furthermore, SIRT1-specific inhibitor EX527 was applied to confirm the role of SIRT1 in the antithrombotic effect of W pigra. RESULTS: W pigra significantly decreased thrombus weight. W pigra had no effects on blood cell counts, whole blood viscosity, blood coagulation, blood fibrinolysis. However, it reduced tissue factor protein expression in the vein wall and thrombus. Moreover, it sharply increased SIRT1 protein expression and decreased leukocytes recruitment in the thrombus and vein wall, serum levels of interleukin-1ß and tumor necrosis factor-α, and protein expressions of Ace-p65 and p-p65. Furthermore, the antithrombotic effect of W pigra was significantly abolished by EX527. CONCLUSIONS: Aqueous extract of W pigra effectively reduced DVT burden by inhibiting inflammation via SIRT1/nuclear factor-kappa B signaling 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.

Angiographic Characteristics and Endovascular Treatment of Anterior Cerebral Artery A1 Segment Aneurysms.

OBJECTIVE: This report aimed to review the angiographic characteristics and evaluate the safety and feasibility of endovascular treatment of A1 aneurysms. METHODS: Nineteen ruptured and 13 unruptured A1 aneurysms treated endovascularly were evaluated in this study. The angiographic and clinical records were retrospectively reviewed. RESULTS: Endovascular treatments were successfully applied in all 32 aneurysms. Conventional coiling was performed in 24 aneurysms, stent-assisted coiling in 7, and solo stenting in 1. The immediate angiographic result was 1 aneurysm in 15, two aneurysms in 10, and 3 in 7 aneurysms according to the Raymond grade. Intraoperative rupture was detected in 1 case without clinical consequence, and no other procedure-related complication occurred. Angiographic follow-up (mean, 12 months; range, 2-42 months) of 25 aneurysms showed total occlusion in 20, improvement in 1, stability in 3, and recurrence in 1. The only recurrence was detected in a case treated using conventional coiling, and it was retreated with stent-assisted coiling. Clinical follow-up (mean, 25 months; range, 6-93 months) was available in 24 of 30 patients, and the modified Rankin Scale score was 0-1 in 22 patients. CONCLUSIONS: Endovascular treatment is technically feasible and safe for A1 aneurysms.

Bioactive glycosides from the roots of Ilex asprella.

Context The roots of Ilex asprella (Hook. et Arn.) Champ. ex Benth. (Aquifoliaceae) are widely used in Chinese medicine to treat influenza, amygdalitis, pertussis, etc. Their mechanism of action is still unknown, which raises the need to identify new bioactive compounds in this plant. Objective In this study, we isolated a novel saponin containing sulphonic groups, namely, asprellcoside A (1) and a known phenolic glycoside compound (2) from the roots of Ilex asprella and evaluated their bioactivities. Materials and methods Molecular structures were elucidated by analysing their spectral and chemical properties. The viability of A549 cells was tested using a MTT assay. Ability of the compounds to inhibit viruses was determined using the neuraminidase activity assay. Their anti-inflammatory effects were tested using the IP-10 activity assay using various concentrations (compound 1: 0.6, 0.2, 0.6, 1.70, 5.00 and 15.00 µM; compound 2: 0.4, 1.2, 3.6, 11.0, 33.0 and 100 µM). Their inhibitory effect on platelet aggregation induced by adenosine diphosphate (ADP) in rabbit plasma was determined at 60 and 80 µM. Results Both compounds inhibit influenza virus strain A/PuertoRico/8/1934 (H1N1) strongly with EC50 values of 4.1 and 1.7 µM, respectively. Both compounds inhibit the secretion of IP-10 with EC50 values of 6.6 and 2.5 µM, respectively. Compound 1 alone inhibited platelet aggregation significantly, with the rate of suppression being 47 ± 8 and 38 ± 3%, at 60 and 80 µM, respectively. Conclusions The results suggest that both compounds may be valid therapeutics against influenza virus infection and that compound 1 may be a novel agent for treating thrombosis.

Treatment of fenestrated vertebrobasilar junction-related aneurysms with endovascular techniques.

Fenestrated vertebrobasilar junction-related aneurysms (fVBJ-AN) are uncommon and endovascular management strategies have become the first options for the treatment of these lesions. This clinical study aimed to report our experience in the endovascular management of these lesions and to review the literature. We retrospectively reviewed 10 consecutive patients harboring 12 fVBJ-AN between January 2007 and December 2014. The demographic, angiographic and clinical data were reviewed. Additionally, a literature review was performed. Endovascular management strategies were successfully applied in all 10 patients. Post-procedural angiograms indicated total occlusion in eight (66.7%) aneurysms, a residual neck in one (8.3%) aneurysm, and three residual aneurysms (25%). No procedure-related complications were observed. Follow-up angiograms were obtained in eight patients and revealed nine occluded aneurysms and one improved aneurysm; two patients were lost to angiographic follow-up. Clinical follow-ups were obtained in all patients (until July 2015), and the modified Rankin Scale scores at 69.5months (range 17-101months) of follow-up were 0 in eight patients and 1 in two patients. Endovascular management strategies provided a high occlusion rate and an acceptable complication rate and are thus efficacious in the treatment of fVBJ-AN. Further studies are necessary to validate the utility of these treatments due to the low incidence of fVBJ-AN.

Parametric Digital Subtraction Angiography Imaging for the Objective Grading of Collateral Flow in Acute Middle Cerebral Artery Occlusion.

PURPOSE: To report the feasibility of parametric color-coded digital subtraction angiography (DSA) in complementing the traditional, subjective way of leptomeningeal collateral assessment in acute middle cerebral artery (MCA) occlusions. METHODS: Thirty-three consecutive patients with acute MCA occlusion who received endovascular treatment were recruited for investigation. Eighteen of 33 consecutive patients were included. The target downstream territory (TDT) of MCA and reference point at terminal internal carotid artery of each patient was contoured by 5 raters independently on the basis of anteroposterior 2-dimensional DSA. Two parameters of relative maximum density of TDT (rDensitymax) and peak time interval (ΔPT) between reference and TDT were extracted by the use of parametric DSA analysis software. Interrater reliability was tested with intraclass correlation coefficients. Parameters with sufficient interrater reliability entered validity evaluation. Then, the correlation test with the American Society of Interventional and Therapeutic Neuroradiology collateral grading system and efficacy in predicting favorable clinical outcome was evaluated. RESULTS: The intraclass correlation coefficient of rDensitymax and ΔPT were 0.983, 95% confidence interval 0.968-0.993 and 0.831, 95% confidence interval 0.705-0.923, respectively. The parameter rDensitymax showed a strong correlation with the American Society of Interventional and Therapeutic Neuroradiology collateral grading system score (r of Spearman correlation test = 0.869, P < 0.001) and mRS at 3 months (partial correlation coefficient = 0.616, P = 0.009), whereas ΔPT_average did not. A cut-off point of 0.224 in rDensitymax predicted a favorable clinical outcome with high sensitivity and specificity. CONCLUSIONS: The relative maximum contrast density of MCA territory on 2-dimensional DSA measured by parametric imaging technique appears to be a simple and reliable metric for the assessment of leptomeningeal collaterals in cases of acute MCA occlusion.

Treatment of ruptured vertebral artery dissecting aneurysms distal to the posterior inferior cerebellar artery: stenting or trapping?

PURPOSE: The treatment of ruptured vertebral artery dissecting aneurysms (VADAs) continues to be controversial. Our goal was to evaluate the safety, efficacy, and long-term outcomes of internal trapping and stent-assisted coiling (SAC) for ruptured VADAs distal to the posterior inferior cerebellar artery (supra-PICA VADAs), which is the most common subset. METHODS: A retrospective review was conducted of 39 consecutive ruptured supra-PICA VADAs treated with internal trapping (n = 20) or with SAC (n = 19) at our institution. The clinical and angiographic data were retrospectively compared. RESULTS: The immediate total occlusion rate of the VADAs was 80 % in the trapping group, which improved to 88.9 % at the follow-ups (45 months on average). Unwanted occlusions of the posterior inferior cerebellar artery (PICA) were detected in three trapped cases. Incomplete obliteration of the VADA or unwanted occlusions of the PICA were detected primarily in the VADAs closest to the PICA. In the stenting group, the immediate total occlusion rate was 47.4 %, which improved to 100 % at the follow-ups (39 months on average). The immediate total occlusion rate of the VADAs was higher in the trapping group (p < 0.05), but the later total occlusion was slightly higher in the stenting group (p > 0.05). CONCLUSIONS: Our preliminary results showed that internal trapping and stent-assisted coiling are both technically feasible for treating ruptured supra-PICA VADAs. Although not statistically significant, procedural related complications occurred more frequently in the trapping group. When the VADAs are close to the PICA, we suggest that the lesions should be treated using SAC.