Highly pathogenic avian influenza A virus H5N1 NS1 protein induces caspase-dependent apoptosis in human alveolar basal epithelial cells

<p>Abstract</p> <p>Background</p> <p>It is widely considered that the multifunctional NS1 protein of influenza A viruses contributes significantly disease pathogenesis by modulating a number of virus and host-cell processes, but it is highly controversial whether this non-structural protein is a proapoptotic or antiapoptotic factor in infected cells.</p> <p>Results</p> <p>NS1 protein of influenza A/chicken/Jilin/2003 virus, a highly pathogenic H5N1 strain, could induce apoptosis in the carcinomic human alveolar basal epithelial cells (A549) by electron microscopic and flow cytometric analyses. NS1 protein-triggered apoptosis in A549 cells is via caspase-dependent pathway.</p> <p>Conclusions</p> <p>Influenza A virus NS1 protein serves as a strong inducer of apoptosis in infected human respiratory epithelial cells and plays a critical role in disease pathogenesis.</p

Toll-like receptor activation by helminths or helminth products to alleviate inflammatory bowel disease

Helminth infection may modulate the expression of Toll like receptors (TLR) in dendritic cells (DCs) and modify the responsiveness of DCs to TLR ligands. This may regulate aberrant intestinal inflammation in humans with helminthes and may thus help alleviate inflammation associated with human inflammatory bowel disease (IBD). Epidemiological and experimental data provide further evidence that reducing helminth infections increases the incidence rate of such autoimmune diseases. Fine control of inflammation in the TLR pathway is highly desirable for effective host defense. Thus, the use of antagonists of TLR-signaling and agonists of their negative regulators from helminths or helminth products should be considered for the treatment of IBD

The NS1 protein of influenza a virus interacts with heat shock protein Hsp90 in human alveolar basal epithelial cells: Implication for virus-induced apoptosis

<p>Abstract</p> <p>Background</p> <p>Our previous study showed that the NS1 protein of highly pathogenic avian influenza A virus H5N1 induced caspase-dependent apoptosis in human alveolar basal epithelial cells (A549), supporting its function as a proapoptotic factor during viral infection, but the mechanism is still unknown.</p> <p>Results</p> <p>To characterize the mechanism of NS1-induced apoptosis, we used a two-hybrid system to isolate the potential NS1-interacting partners in A549 cells. We found that heat shock protein 90 (Hsp90) was able to interact with the NS1 proteins derived from both H5N1 and H3N2 viruses, which was verified by co-immunoprecitation assays. Significantly, the NS1 expression in the A549 cells dramatically weakened the interaction between Apaf-1 and Hsp90 but enhanced its interaction with cytochrome c (Cyt c), suggesting that the competitive binding of NS1 to Hsp90 might promote the Apaf-1 to associate with Cyt c and thus facilitate the activation of caspase 9 and caspase 3.</p> <p>Conclusions</p> <p>The present results demonstrate that NS1 protein of Influenza A Virus interacts with heat hock protein Hsp90 and meidates the apoptosis induced by influenza A virus through the caspase cascade.</p

A new therapeutic strategy for lung tissue injury induced by influenza with CR2 targeting complement inhibitior

<p>Abstract</p> <p>Background</p> <p>Influenza is a respiratory disease that seriously threatens human health. In fact, influenza virus itself does not make critical contribution to mortality induced by influenza, but "cytokine storm" produced by the excessive immune response triggered by the virus can result in inflammatory reaction of lung tissues and fatal lung tissue injury, and thus increase influenza mortality. Therefore, besides antiviral drugs, immunosuppression drugs should also be included in infection treatment.</p> <p>Presentation of the hypothesis</p> <p>Complement is the center of inflammatory reaction. If complement system is over activated, the body will have strong inflammatory reaction or tissue injury, resulting in pathological process. Many studies have proved that, inflammatory injury of lung tissues caused by influenza virus is closely related to complement activation. Therefore, inhibiting complement activation can significantly reduce inflammatory injury in lung tissues. As complement is both a physiological defense and pathological damage medium, systematic inhibition may result in side effects including infection. Therefore, we design targeting complement inhibitors for complement activation sites, i.e. with CR2 as targeting vector, complement inhibitors like CD59 and Crry are targeted to inflammatory sites to specially inhibit the complement activation in local injury, thus local inflammatory reaction is inhibited.</p> <p>Testing the hypothesis</p> <p>CR2-CD59 and CR2-Crry targeting complement inhibitors are fusion-expressed, and their biological activity is examined via in <it>vivo </it>and in vitro tests. CR2 targeting complement inhibitors are used to treat mouse influenza viral pneumonia model, with PBS treatment group as the control. The survival and lung tissue injury of the mice is observed and the effect of CR2 targeting complement inhibitors on pneumonia induced by influenza virus is evaluated.</p> <p>Implications of the hypothesis</p> <p>CR2 targeting complement inhibitors are expected to be ideal drugs for viral pneumonia.</p

Effect of Temperature on Electromagnetic Performance of Active Phased Array Antenna

Active phased array antennas (APAAs) can suffer from the effects of harsh thermal environments, which are caused by the large quantity of power generated by densely packed T/R modules and external thermal impacts. The situation may be worse in the case of limited room and severe thermal loads, due to heat radiation and a low temperature sink. The temperature field of the antenna can be changed. Since large numbers of temperature-sensitive electronic components exist in T/R modules, excitation current output can be significantly affected and the electromagnetic performance of APAAs can be seriously degraded. However, due to a lack of quantitative analysis, it is difficult to directly estimate the effect of temperature on the electromagnetic performance of APAAs. Therefore, this study investigated the electromagnetic performance of APAAs as affected by two key factors—the uniformly distributed temperature field and the temperature gradient field—based on different antenna shapes and sizes, to provide theoretical guidance for their thermal design

Influence of hyperuricemia on the reproductive function of female rats and its mechanism

Objective To investigate the influence of hyperuricemia (HUA) on the reproductive function of female rats and its mechanism. Methods A total of 18 female Wistar rats were randomly divided into HUA group, HUA recovery group (HR group), and control group (N group), with 6 rats in each group. The rats in the HUA group and the HR group were given intragastric administration of 50 mg/kg uric acid and intraperitoneal injection of 250 mg/kg oteracil potassium every day, and since week 9, the rats in the HR group were given an equal volume of normal saline by gavage and intraperitoneal injection, while the treatment remained unchanged for those in the HUA group, for another 7 weeks; the rats in the N group were given an equal vo-lume of normal saline by gavage and intraperitoneal injection for 16 weeks. At week 16, body weight, uterine mass, and ovarian mass were measured for all three groups, and uterine and ovarian coefficients were calculated; hematoxylin-eosin staining was used to observe the pathological changes of the uterus and ovarian tissue; enzyme-linked immunosorbent assay was used to measure the serum levels of gonadotropin-releasing hormone (GnRH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2); the vaginal exfoliation cell smear method was used to observe the estrous cycle of rats; colorimetry was used to measure the levels of malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH) in uterine tissue of the three groups; immunofluorescence assay was used to measure the fluorescence intensity of tumor necrosis factor-α (TNF-α) in uterine tissue of the three groups. Results Compared with the N group, the HUA group had significant reductions in uterine coefficient, number of follicles, endometrial thickness, and estrous interval, a significant increase in the serum level of FSH, significant reductions in the levels of SOD and GSH in uterine tissue, and a significant increase in the content of MDA (F=7.80-111.40,t=3.95-12.37,P&lt;0.05), as well as an increase in the fluorescence intensity of TNF-α in uterine tissue. Compared with the HUA group, the HR group had significant increases in the number of follicles, endometrial thickness, the serum level of FSH, and the levels of SOD and GSH in uterine tissue and a significant reduction in the level of MDA (t=3.40-11.56,P&lt;0.05), as well as a reduction in the fluorescence intensity of TNF-α in uterine tissue. Conclusion HUA can cause the decline of reproductive function in female rats, which may be associated with the increase in the serum level of uric acid, the disorder of sex hormone secretion, the increase in the level of oxidative stress, and the induction of inflammatory response

Comparative transcriptome analysis reveals the potential mechanism of GA3-induced dormancy release in Suaeda glauca black seeds

Suaeda glauca Bunge produces dimorphic seeds on the same plant, with brown seeds displaying non-dormant characteristics and black seeds exhibiting intermediate physiological dormancy traits. Previous studies have shown that black seeds have a very low germination rate under natural conditions, but exogenous GA3 effectively enhanced the germination rate of black seeds. However, the physiological and molecular mechanisms underlying the effects of GA3 on S. glauca black seeds are still unclear. In this study, transcriptomic profiles of seeds at different germination stages with and without GA3 treatment were analyzed and compared, and the TTF, H2O2, O2–, starch, and soluble sugar contents of the corresponding seed samples were determined. The results indicated that exogenous GA3 treatment significantly increased seed vigor, H2O2, and O2– contents but decreased starch and soluble sugar contents of S. glauca black seeds during seed dormancy release. RNA-seq results showed that a total of 1136 DEGs were identified in three comparison groups and were involved mainly in plant hormone signal transduction, diterpenoid biosynthesis, flavonoid biosynthesis, phenylpropanoid biosynthesis, and carbohydrate metabolism pathway. Among them, the DEGs related to diterpenoid biosynthesis (SgGA3ox1, SgKAO and SgGA2ox8) and ABA signal transduction (SgPP2Cs) could play important roles during seed dormancy release. Most genes involved in phenylpropanoid biosynthesis were activated under GA3 treatment conditions, especially many SgPER genes encoding peroxidase. In addition, exogenous GA3 treatment also significantly enhanced the expression of genes involved in flavonoid synthesis, which might be beneficial to seed dormancy release. In accordance with the decline in starch and soluble sugar contents, 15 genes involved in carbohydrate metabolism were significantly up-regulated during GA3-induced dormancy release, such as SgBAM, SgHXK2, and SgAGLU, etc. In a word, exogenous GA3 effectively increased the germination rate and seed vigor of S. glauca black seeds by mediating the metabolic process or signal transduction of plant hormones, phenylpropanoid and flavonoid biosynthesis, and carbohydrate metabolism processes. Our results provide novel insights into the transcriptional regulation mechanism of exogenous GA3 on the dormancy release of S. glauca black seeds. The candidate genes identified in this study may be further studied and used to enrich our knowledge of seed dormancy and germination

A data-driven mathematical model of multi-drug resistant Acinetobacter baumannii transmission in an intensive care unit

Major challenges remain when attempting to quantify and evaluate the impacts of contaminated environments and heterogeneity in the cohorting of health care workers (HCWs) on hospital infections. Data on the detection rate of multidrug-resistant Acinetobacter baumannii (MRAB) in a Chinese intensive care unit (ICU) were obtained to accurately evaluate the level of environmental contamination and also to simplify existing models. Data-driven mathematical models, including mean-field and pair approximation models, were proposed to examine the comprehensive effect of integrated measures including cohorting, increasing nurse-patient ratios and improvement of environmental sanitation on MRAB infection. Our results indicate that for clean environments and with strict cohorting, increasing the nurse-patient ratio results in an initial increase and then a decline in MRAB colonization. In contrast, in contaminated environments, increasing the nurse-patient ratio may lead to either a consistent increase or an initial increase followed by a decline of MRAB colonization, depending on the level of environmental contamination and the cohorting rate. For developing more effective control strategies, the findings suggest that increasing the cohorting rate and nurse-patient ratio are effective interventions for relatively clean environments, while cleaning the environment more frequently and increasing hand washing rate are suitable measures in contaminated environments