Angiopoietin-1 and keratinocyte growth factor restore the impaired alveolar fluid clearance induced by influenza H5N1 virus infection

Poster Session: Novel TherapeuticsBackground: Acute respiratory distress syndrome (ARDS) caused by high pathogenic avian influenza (HPAI) H5N1 virus infection has resulted in severe illness and high mortality rates among patients. Patients with ARDS are often characterized by impaired alveolar fluid clearance and alveolar edema. An understanding of the mechanism responsible for human alveolar edema will lead to the development of novel therapeutic treatments for ARDS patients. We hypothesized that the paracrine soluble factors angiopoietin-1 (Ang-1) and keratinocyte growth factor (KGF) can resolve alveolar fluid clearance by up-regulating the expression of major sodium and chloride transporters impaired by HPAI H5N1 virus infection. Materials and Methods: Human alveolar epithelial cells grown on transwell inserts were infected with HPAI H5N1 (A/HK/483/97) and low pathogenic avian influenza (LPAI) H1N1 (A/HK/54/98) viruses at MOI 0.1 or incubated with conditioned culture medium containing Ang-1 and/or KGF. At 24 and 48 h post-infection, the rate of alveolar fluid transport and protein permeability across the alveolar epithelium was measured. Protein expression of sodium and chloride transporters (Na-K-ATPase, CFTR, and epithelial sodium channel alpha subunit) was measured by qPCR, ELISA, and Western blot. Results: HPAI H5N1 (A/HK/483/97) virus infection significantly reduced net alveolar fluid transport and protein permeability when compared with H1N1 (A/HK/54/98) virus infection at 24 h post-infection and further reduced it at 48 h post-infection. This reduction in alveolar fluid clearance was associated with a substantial reduction in protein expression of Na-K-ATPase, CFTR, and epithelial sodium channel alpha subunit. The influenza virus–infected cells treated with Ang-1 and KGF restored the impaired alveolar edema fluid clearance and protein permeability after HPAI H5N1 virus infection. Furthermore, the paracrine soluble factors Ang-1 and KGF up-regulated the protein expression of the major sodium and chloride transporters resulting from the HPAI influenza virus infection. Conclusions: The paracrine soluble factors Ang-1 and KGF play an important role in maintaining human alveolar fluid clearance by up-regulating the sodium and chloride transporting systems in human alveolar epithelium. This study enriches the understanding of the development of ARDS in human H5N1 disease and may aid in the development of possible therapeutic applications.published_or_final_versio

Behavioral and Emotional Disorders in Children during the COVID-19 Epidemic.

Since December 2019, health systems around the globe have struggled with an increasing number of cases of a viral respiratory syndrome that emerged in China. The cause is a new strain in the coronavirus family, provisionally named 2019 novel coronavirus (2019-nCoV), SARS-CoV-2 or COVID-19.The European Paediatric Association–Union of National European Paediatric Societies and Associations (EPA-UNEPSA) has established a collaborative working group with key Chinese academic institutions and medical centers with the purpose of facilitating the reciprocal exchange of information and sharing scientific knowledge. The aim of this commentary by the China-EPA-UNEPSA working group is to raise awareness regarding children’s psychological needs during epidemics and report early data collected in the COVID19–affected areas in China during the current outbreak, emphasizing the role of families and caregivers in the timely recognition and management of negative emotions

A comparative study of clinical presentation and risk factors for adverse outcome in patients hospitalised with acute respiratory disease due to MERS coronavirus or other causes

Middle East Respiratory syndrome (MERS) first emerged in Saudi Arabia in 2012 and remains a global health concern. The objective of this study was to compare the clinical features and risk factors for adverse outcome in patients with RT-PCR confirmed MERS and in those with acute respiratory disease who were MERS-CoV negative, presenting to the King Fahad Medical City (KFMC) in Riyadh between October 2012 and May 2014. The demographics, clinical and laboratory characteristics and clinical outcomes of patients with RT-PCR confirmed MERS-CoV infection was compared with those testing negative MERS-CoV PCR. Health care workers (HCW) with MERS were compared with MERS patients who were not health care workers. One hundred and fifty nine patients were eligible for inclusion. Forty eight tested positive for MERS CoV, 44 (92%) being hospital acquired infections and 23 were HCW. There were 111 MERS-CoV negative patients with acute respiratory illnesses included in this study as 'negative controls'. Patient with confirmed MERS-CoV infection were not clinically distinguishable from those with negative MERS-CoV RT-PCR results although diarrhoea was commoner in MERS patients. A high level of suspicion in initiating laboratory tests for MERS-CoV is therefore indicated. Variables associated with adverse outcome were older age and diabetes as a co-morbid illness. Interestingly, co-morbid illnesses other than diabetes were not significantly associated with poor outcome. Health care workers with MERS had a markedly better clinical outcome compared to non HCW MERS patients.published_or_final_versio

An environmentally friendly solution-processed ZrLaO gate dielectric for large-area applications in the harsh radiation environment

In this work, an eco-friendly aqueous solution-processed ZrLaO dielectric is demonstrated for large-area application in the harsh radiation environment. Appropriate La doping (10% La) into ZrOx could suppress the formation of Vo and improve the InOx/ZrLaO interface. The Zr0.9La0.1Oy thin films remained stable under 144 krad (SiO2) gamma-ray irradiation, no distinct composition variation or property degradation were observed. The resistor-loaded inverter based on InOx/Zr0.9La0.1Oy TFT demonstrated full swing characteristics with a gain of 13.3 at 4 V and remained 91% gain after 103 krad (SiO2) irradiation

On the Morphology, Structure and Field Emission Properties of Silver-Tetracyanoquinodimethane Nanostructures

Silver-tetracyanoquinodimethane(Ag-TCNQ) nanostructured arrays with different morphologies were grown by an organic vapor-transport reaction under different conditions. The field emission properties of nanostructured arrays were studied systematically. Their morphology and crystal structure were characterized by SEM and XRD, respectively. It was found that the field emission properties were strongly dependent on the reaction temperature and the initial Ag film thickness. The lowest turn-on field with 10-nm-thick silver film is about 2.0 V/μm, comparable to that of carbon nanotubes. The film crystal structure and the morphology are contributed to the final emission performance

Two Prp19-Like U-Box Proteins in the MOS4-Associated Complex Play Redundant Roles in Plant Innate Immunity

Plant Resistance (R) proteins play an integral role in defense against pathogen infection. A unique gain-of-function mutation in the R gene SNC1, snc1, results in constitutive activation of plant immune pathways and enhanced resistance against pathogen infection. We previously found that mutations in MOS4 suppress the autoimmune phenotypes of snc1, and that MOS4 is part of a nuclear complex called the MOS4-Associated Complex (MAC) along with the transcription factor AtCDC5 and the WD-40 protein PRL1. Here we report the immuno-affinity purification of the MAC using HA-tagged MOS4 followed by protein sequence analysis by mass spectrometry. A total of 24 MAC proteins were identified, 19 of which have predicted roles in RNA processing based on their homology to proteins in the Prp19-Complex, an evolutionarily conserved spliceosome-associated complex containing homologs of MOS4, AtCDC5, and PRL1. Among these were two highly similar U-box proteins with homology to the yeast and human E3 ubiquitin ligase Prp19, which we named MAC3A and MAC3B. MAC3B was recently shown to exhibit E3 ligase activity in vitro. Through reverse genetics analysis we show that MAC3A and MAC3B are functionally redundant and are required for basal and R protein–mediated resistance in Arabidopsis. Like mos4-1 and Atcdc5-1, mac3a mac3b suppresses snc1-mediated autoimmunity. MAC3 localizes to the nucleus and interacts with AtCDC5 in planta. Our results suggest that MAC3A and MAC3B are members of the MAC that function redundantly in the regulation of plant innate immunity

Climate Variability and Hemorrhagic Fever with Renal Syndrome Transmission in Northeastern China

Background: The transmission of hemorrhagic fever with renal syndrome (HFRS) is influenced by climatic variables. However, few studies have examined the quantitative relationship between climate variation and HFRS transmission. ---------- Objective: We examined the potential impact of climate variability on HFRS transmission and developed climate-based forecasting models for HFRS in northeastern China. ---------- Methods: We obtained data on monthly counts of reported HFRS cases in Elunchun and Molidawahaner counties for 1997–2007 from the Inner Mongolia Center for Disease Control and Prevention and climate data from the Chinese Bureau of Meteorology. Cross-correlations assessed crude associations between climate variables, including rainfall, land surface temperature (LST), relative humidity (RH), and the multivariate El Niño Southern Oscillation (ENSO) index (MEI) and monthly HFRS cases over a range of lags. We used time-series Poisson regression models to examine the independent contribution of climatic variables to HFRS transmission. ----------- Results: Cross-correlation analyses showed that rainfall, LST, RH, and MEI were significantly associated with monthly HFRS cases with lags of 3–5 months in both study areas. The results of Poisson regression indicated that after controlling for the autocorrelation, seasonality, and long-term trend, rainfall, LST, RH, and MEI with lags of 3–5 months were associated with HFRS in both study areas. The final model had good accuracy in forecasting the occurrence of HFRS. ---------- Conclusions: Climate variability plays a significant role in HFRS transmission in northeastern China. The model developed in this study has implications for HFRS control and prevention

Spatiotemporal Dynamics of Hemorrhagic Fever with Renal Syndrome, Beijing, People's Republic of China

We used geographic information systems to characterize the dynamic change in spatial distribution of hemorrhagic fever with renal syndrome (HFRS) in Beijing, People's Republic of China. The seasonal variation in its incidence was observed by creating an epidemic curve. HFRS was associated with developed land, orchards, and rice paddies

Withanolides-Induced Breast Cancer Cell Death Is Correlated with Their Ability to Inhibit Heat Protein 90

Withanolides are a large group of steroidal lactones found in Solanaceae plants that exhibit potential anticancer activities. We have previously demonstrated that a withanolide, tubocapsenolide A, induced cycle arrest and apoptosis in human breast cancer cells, which was associated with the inhibition of heat shock protein 90 (Hsp90). To investigate whether other withanolides are also capable of inhibiting Hsp90 and to analyze the structure-activity relationships, nine withanolides with different structural properties were tested in human breast cancer cells MDA-MB-231 and MCF-7 in the present study. Our data show that the 2,3-unsaturated double bond-containing withanolides inhibited Hsp90 function, as evidenced by selective depletion of Hsp90 client proteins and induction of Hsp70. The inhibitory effect of the withanolides on Hsp90 chaperone activity was further confirmed using in vivo heat shock luciferase activity recovery assays. Importantly, Hsp90 inhibition by the withanolides was correlated with their ability to induce cancer cell death. In addition, the withanolides reduced constitutive NF-κB activation by depleting IκB kinase complex (IKK) through inhibition of Hsp90. In estrogen receptor (ER)-positive MCF-7 cells, the withanolides also reduced the expression of ER, and this may be partly due to Hsp90 inhibition. Taken together, our results suggest that Hsp90 inhibition is a general feature of cytotoxic withanolides and plays an important role in their anticancer activity