Detoxification of insecticides,allechemicals and heavy metals by glutathione S‐transferase SlGSTE1 in the gut of Spodoptera litura

Insect glutathione S‐transferases (GSTs) play important roles in detoxifying toxic compounds and eliminating oxidative stress caused by these compounds. In this study, detoxification activity of the epsilon GST SlGSTE1 in Spodoptera litura was analyzed for several insecticides and heavy metals. SlGSTE1 was significantly up‐regulated by chlorpyrifos and xanthotoxin in the midgut of S. litura. The recombinant SlGSTE1 had V_max (reaction rate of the enzyme saturated with the substrate) and K_m (michaelis constant and equals to the substrate concentration at half of the maximum reaction rate of the enzyme) values of 27.95 ± 0.88 μmol/min/mg and 0.87 ± 0.028 mmol/L for glutathione, respectively, and V_max and K_m values of 22.96 ± 0.78 μmol/min/mg and 0.83 ± 0.106 mmol/L for 1‐chloro‐2,4‐dinitrobenzene, respectively. In vitro enzyme indirect activity assay showed that the recombinant SlGSTE1 possessed high binding activities to the insecticides chlorpyrifos, deltamethrin, malathion, phoxim and dichloro‐diphenyl‐trichloroethane (DDT). SlGSTE1 showed higher binding activity to toxic heavy metals cadmium, chromium and lead than copper and zinc that are required for insect normal growth. Western blot analysis showed that SlGSTE1 was induced in the gut of larvae fed with chlorpyrifos or cadmium. SlGSTE1 also showed high peroxidase activity. All the results together indicate that SlGSTE1 may play an important role in the gut of S. litura to protect the insect from the toxic effects of these compounds and heavy metals.     

Second-Hand Cigarette Smoke Impairs Bacterial Phagocytosis in Macrophages by Modulating CFTR Dependent Lipid-Rafts

Introduction

First/Second-hand cigarette-smoke (FHS/SHS) exposure weakens immune defenses inducing chronic obstructive pulmonary disease (COPD) but the underlying mechanisms are not fully understood. Hence, we evaluated if SHS induced changes in membrane/lipid-raft (m-/r)-CFTR (cystic fibrosis transmembrane conductance regulator) expression/activity is a potential mechanism for impaired bacterial phagocytosis in COPD.

Methods

RAW264.7 murine macrophages were exposed to freshly prepared CS-extract (CSE) containing culture media and/or Pseudomonas-aeruginosa-PA01-GFP for phagocytosis (fluorescence-microscopy), bacterial survival (colony-forming-units-CFU), and immunoblotting assays. The CFTR-expression/activity and lipid-rafts were modulated by transient-transfection or inhibitors/inducers. Next, mice were exposed to acute/sub-chronic-SHS or room-air (5-days/3-weeks) and infected with PA01-GFP, followed by quantification of bacterial survival by CFU-assay.

Results

We investigated the effect of CSE treatment on RAW264.7 cells infected by PA01-GFP and observed that CSE treatment significantly (p<0.01) inhibits PA01-GFP phagocytosis as compared to the controls. We also verified this in murine model, exposed to acute/sub-chronic-SHS and found significant (p<0.05, p<0.02) increase in bacterial survival in the SHS-exposed lungs as compared to the room-air controls. Next, we examined the effect of impaired CFTR ion-channel-activity on PA01-GFP infection of RAW264.7 cells using CFTR172-inhibitor and found no significant change in phagocytosis. We also similarly evaluated the effect of a CFTR corrector-potentiator compound, VRT-532, and observed no significant rescue of CSE impaired PA01-GFP phagocytosis although it significantly (p<0.05) decreases CSE induced bacterial survival. Moreover, induction of CFTR expression in macrophages significantly (p<0.03) improves CSE impaired PA01-GFP phagocytosis as compared to the control. Next, we verified the link between m-/r-CFTR expression and phagocytosis using methyl-β-cyclodextran (CD), as it is known to deplete CFTR from membrane lipid-rafts. We observed that CD treatment significantly (p<0.01) inhibits bacterial phagocytosis in RAW264.7 cells and adding CSE further impairs phagocytosis suggesting synergistic effect on CFTR dependent lipid-rafts.

Conclusion

Our data suggest that SHS impairs bacterial phagocytosis by modulating CFTR dependent lipid-rafts.     

DomeTree: a canonical toolkit for mitochondrial DNA analyses in domesticated animals

Mitochondrial DNA (mtDNA) is widely used in various genetic studies of domesticated animals. Many applications require comprehensive knowledge about the phylogeny of mtDNA variants. Herein, we provide the most up‐to‐date mtDNA phylogeny (i.e. haplogroup tree or matrilineal genealogy) and a standardized hierarchical haplogroup nomenclature system for domesticated cattle, dogs, goats, horses, pigs, sheep, yaks and chickens. These high‐resolution mtDNA haplogroup trees based on 1240 complete or near‐complete mtDNA genome sequences are available in open resource DomeTree ( http://www.dometree.org ). In addition, we offer the software MitoToolPy ( http://www.mitotool.org/mp.html ) to facilitate the mtDNA data analyses. We will continuously and regularly update DomeTree and MitoToolPy.     

Seroprevalence of the Hepatitis B,Hepatitis C,and Human Immunodeficiency Viruses and Treponema pallidum at the Beijing General Hospital from 2010 to 2014: A Cross-Sectional Study

BackgroundThe hepatitis B, hepatitis C, human immunodeficiency viruses and Treponema pallidum are important causes of infectious diseases concern to public health.MethodsBetween 2010 and 2014, we used an automated chemiluminescence microparticle immunoassay to detect the hepatitis B, hepatitis C, and human immunodeficiency viruses as well as Treponema pallidum (the rapid plasma regain test was used in 2010–2011). Positive human immunodeficiency virus tests were confirmed via western blotting.ResultsAmong 416,130 subjects, the seroprevalences for hepatitis B virus, hepatitis C virus, human immunodeficiency virus, and Treponema pallidum were 5.72%, 1.23%, 0.196%, and 0.76%, respectively. Among 671 patients with positive human immunodeficiency virus results, 392 cases were confirmed via western blotting. Hepatitis B and human immunodeficiency virus infections were more frequent in men (7.78% and 0.26%, respectively) than in women (4.45% and 0.021%, respectively). The hepatitis B and C virus seroprevalences decreased from 6.21% and 1.58%, respectively, in 2010, to 5.37% and 0.988%, respectively, in 2014. The human immunodeficiency virus seroprevalence increased from 0.04% in 2010 to 0.17% in 2014, and was elevated in the Infectious Disease (2.65%), Emergency (1.71%), and Dermatology and Sexually Transmitted Diseases (1.12%) departments. The specificity of the human immunodeficiency virus screening was 71.4%. The false positive rates for the Treponema pallidum screening tests increased in patients who were 60–70 years old. The co-infection rates for the hepatitis C and human immunodeficiency viruses were 0.47% in hepatitis C virus-positive patients and 7.33% in human immunodeficiency virus-positive patients.ConclusionsDuring 2010–2014, hepatitis B virus and human immunodeficiency virus infections were more frequent among men at our institution. Although the seroprevalences of hepatitis B and C viruses decreased, the seroprevalence of human immunodeficiency virus infection increased (with higher seroprevalences in high-risk departments). Older patients were more likely to exhibit false positive findings for syphilis.     

Prophylactic Use of Macrolide Antibiotics for the Prevention of Chronic Obstructive Pulmonary Disease Exacerbation: A Meta-Analysis

Background

Acute exacerbations of chronic obstructive pulmonary disease (AECOPDs) can lead to high frequencies and rates of hospitalization and mortality. Macrolides are a class of antibiotics that possess both antimicrobial and anti-inflammatory properties. Since the occurrence of AECOPDs is associated with aggravation of airway inflammation and bacterial infections, prophylactic macrolide treatment may be an effective approach towards the prevention of AECOPDs.

Methods

We systemically searched the PubMed, Embase and Cochrane Library databases to identify randomized controlled trials (RCTs) that evaluated the effect of prophylactic macrolide therapy on the prevention of AECOPDs. The primary outcomes were the total number of patients with one or more exacerbations as well as the rate of exacerbations per patient per year.

Results

Nine RCTs comprising 1666 patients met the inclusion criteria. Pooled evidence showed macrolides could reduce the frequency of exacerbations in patients with COPD by both unweighted (RR = 0.70; 95% CI: 0.56–0.87; P < 0.01) and weighted approaches (RR = 0.58, 95% CI: 0.43–0.78, P < 0.01). Subgroup analysis showed only 6–12 months of erythromycin or azithromycin therapy could be effective. Moreover, among studies with 6–12 months of azithromycin therapy, both the daily dosing regimen and the intermittent regimen significantly reduced exacerbation rates. The overall number of hospitalizations and the all-cause rate of death were not significantly different between the treatment and control groups. A tendency for more adverse events was found in the treatment groups (OR = 1.55, 95%CI: 1.003–2.39, P = 0.049).

Conclusions

Our results suggest 6-12 months erythromycin or azithromycin therapy could effectively reduce the frequency of exacerbations in patients with COPD. However, Long-term treatment may bring increased adverse events and the emergence of macrolide-resistance. A recommendation for the prophylactic use of macrolide therapy should weigh both the advantages and disadvantages.     

The Role of China in the Global Spread of the Current Cholera Pandemic

Epidemics and pandemics of cholera, a severe diarrheal disease, have occurred since the early 19th century and waves of epidemic disease continue today. Cholera epidemics are caused by individual, genetically monomorphic lineages of Vibrio cholerae: the ongoing seventh pandemic, which has spread globally since 1961, is associated with lineage L2 of biotype El Tor. Previous genomic studies of the epidemiology of the seventh pandemic identified three successive sub-lineages within L2, designated waves 1 to 3, which spread globally from the Bay of Bengal on multiple occasions. However, these studies did not include samples from China, which also experienced multiple epidemics of cholera in recent decades. We sequenced the genomes of 71 strains isolated in China between 1961 and 2010, as well as eight from other sources, and compared them with 181 published genomes. The results indicated that outbreaks in China between 1960 and 1990 were associated with wave 1 whereas later outbreaks were associated with wave 2. However, the previously defined waves overlapped temporally, and are an inadequate representation of the shape of the global genealogy. We therefore suggest replacing them by a series of tightly delineated clades. Between 1960 and 1990 multiple such clades were imported into China, underwent further microevolution there and then spread to other countries. China was thus both a sink and source during the pandemic spread of V. cholerae, and needs to be included in reconstructions of the global patterns of spread of cholera.     

Effect of Dexmedetomidine on Preventing Postoperative Agitation in Children: A Meta-Analysis

Background

Emergence agitation (EA) is one of the most common postoperative complications in children. The purpose of this meta-analysis is to assess the effect of dexmedetomidine for preventing postoperative agitation in children.

Methods

We searched the Cochrane Central Register of Controlled Trails, MEDLINE, and EMBASE. Randomized controlled trials were included. The following outcome measures were evaluated: incidence of EA, number of patients requiring rescue, time to eye-open, time to extubation, time to discharge from the postanesthesia care unit (PACU).

Results

We analyzed 19 trials (1608 patients) that met the inclusion criteria. Compared with placebo, intravenous dexmedetomidine significantly reduced the incidence of EA [risk ratio (RR) 0.34, 95% confidence interval (CI) 0.25–0.44, P<0.00001). Dexmedetomidine also decreased the incidence of severe pain (RR 0.41, 95% CI 0.27–0.62, P<0.0001) and requirement of a rescue drug (RR 0.31, 95% CI 0.18–0.53, P<0.0001). However, compared with placebo, dexmedetomidine increased the time to eye-open by 0.98 min (P = 0.01) and the time to PACU discharge by 4.63 min (P = 0.02). Dexmedetomidine was also compared with midazolam, propofol, ketamine, and fentanyl, among others. No significant difference was found in the incidence of EA for most of these comparisons, with the exception of fentanyl and propofol, where dexmedetomidine was more beneficial.

Conclusions

Dexmedetomidine was proved effective for preventing EA and for reducing severe pain and the requirement of rescue drugs. It slightly increased the time to eye-open and the time to PACU discharge. Dexmedetomidine was also more beneficial than propofol or fentanyl in preventing EA.