A strategy for emergency treatment of Schistosoma japonicum-infested water

<p>Abstract</p> <p>Background</p> <p>Schistosomiasis japonica, caused by contact with <it>Schistosoma japonicum </it>cercaria-infested water when washing, bathing or production, remains a major public-health concern in China. The purpose of the present study was to investigate the effect of a suspension concentrate of niclosamide (SCN) on killing cercaria of <it>S. japonicum </it>that float on the water surface, and its toxicity to fish, so as to establish an emergency-treatment intervention for rapidly killing cercaria and eliminating water infectivity.</p> <p>Results</p> <p>At 30 min after spraying 100 mg/L SCN, with niclosamide dosages of 0.01, 0.02, 0.03, 0.04 g/m², the water infectivity reduced significantly and no infectivity was found at 60 min after spraying SCN. The surface of static water was sprayed with 100 mg/L SCN, the peak concentration was found at 0 min, and the solution diffused to site with a water depth of 10 cm after 10 min. 30 min later, SCN diffused to the whole water body, and distributed evenly. After spraying 100 mg/L SCN onto the surface of the water with a volume of(3.14 × 20²×50)cm³, with niclosamide dosages of 0.02 g/m², 96 h later, no death of zebra fish was observed.</p> <p>Conclusions</p> <p>By spraying 100 mg/L SCN, with a niclosamide dosage of 0.02 g/m²onto the surface of <it>S. japonicum</it>-infested water, infectivity of the water can be eliminated after 30-60 min, and there is no evident toxicity to fish. This cercaria-killing method, as an emergency-treatment intervention for infested water, can be applied in those forecasting and early warning systems for schistosomiasis.</p

Observation of a ppb mass threshoud enhancement in \psi^\prime\to\pi^+\pi^-J/\psi(J/\psi\to\gamma p\bar{p}) decay

The decay channel $\psi^\prime\to\pi^+\pi^-J/\psi(J/\psi\to\gamma p\bar{p})$ is studied using a sample of $1.06\times 10^8$ $\psi^\prime$ events collected by the BESIII experiment at BEPCII. A strong enhancement at threshold is observed in the $p\bar{p}$ invariant mass spectrum. The enhancement can be fit with an $S$-wave Breit-Wigner resonance function with a resulting peak mass of $M=1861^{+6}_{-13} {\rm (stat)}^{+7}_{-26} {\rm (syst)} {\rm MeV/}c^2$ and a narrow width that is $\Gamma<38 {\rm MeV/}c^2$ at the 90% confidence level. These results are consistent with published BESII results. These mass and width values do not match with those of any known meson resonance.Comment: 5 pages, 3 figures, submitted to Chinese Physics

Activin B Promotes Epithelial Wound Healing In Vivo through RhoA-JNK Signaling Pathway

Background: Activin B has been reported to promote the proliferation and migration of keratinocytes in vitro via the RhoA-JNK signaling pathway, whereas its in vivo role and mechanism in wound healing process has not yet been elucidated. Principal Findings: In this study, we explored the potential mechanism by which activin B induces epithelial wound healing in mice. Recombinant lentiviral plasmids, with RhoA (N19) and RhoA (L63) were used to infect wounded KM mice. The wound healing process was monitored after different treatments. Activin B-induced cell proliferation on the wounded skin was visualized by electron microscopy and analyzed by 59-bromodeoxyuridine (BrdU) incorporation assay. Protein expression of p-JNK or p-cJun was determined by immunohistochemical staining and immunoblotting analysis. Activin B efficiently stimulated the proliferation of keratinocytes and hair follicle cells at the wound area and promoted wound closure. RhoA positively regulated activin B-induced wound healing by up-regulating the expression of p-JNK and p-cJun. Moreover, suppression of RhoA activation delayed activin B-induced wound healing, while JNK inhibition recapitulated phenotypes of RhoA inhibition on wound healing. Conclusion: These results demonstrate that activin B promotes epithelial wound closure in vivo through the RhoA-Rock

Differences in carotid arterial morphology and composition between individuals with and without obstructive coronary artery disease: A cardiovascular magnetic resonance study

Objective: We sought to determine differences with cardiovascular magnetic resonance (CMR) in the morphology and composition of the carotid arteries between individuals with angiographically-defined obstructive coronary artery disease (CAD, = 50% stenosis, cases) and those with angiographically normal coronaries (no lumen irregularities, controls). Methods and results: 191 participants (50.3% female; 50.8% CAD cases) were imaged with a multi-sequence, carotid CMR protocol at 1.5T. For each segment of the carotid, lumen area, wall area, total vessel area (lumen area + wall area), mean wall thickness and the presence or absence of calcification and lipid-rich necrotic core were recorded bilaterally. In male CAD cases compared to male controls, the distal bulb had a significantly smaller lumen area (60.0 [plus or minus] 3.1 vs. 79.7 [plus or minus] 3.2 mm[super]2, p less than 0.001) and total vessel area (99.6 [plus or minus] 4.0 vs. 119.8 [plus or minus] 4.1 mm[super]2; p less than 0.001), and larger mean wall thickness (1.25 [plus or minus] 0.03 vs. 1.11 [plus or minus] 0.03 mm; p = 0.002). Similarly, the internal carotid had a smaller lumen area (37.5 [plus or minus] 1.8 vs. 44.6 [plus or minus] 1.8 mm[super]2; p = 0.006) and smaller total vessel area (64.0 [plus or minus] 2.3 vs. 70.9 [plus or minus] 2.4 mm[super]2; p = 0.04). These metrics were not significantly different between female groups in the distal bulb and internal carotid or for either gender in the common carotid. Male CAD cases had an increased prevalence of lipid-rich necrotic core (49.0% vs. 19.6%; p = 0.003), while calcification was more prevalent in both male (46.9% vs. 17.4%; p = 0.002) and female (33.3% vs. 14.6%; p = 0.031) CAD cases compared to controls. Conclusion: Males with obstructive CAD compared to male controls had carotid bulbs and internal carotid arteries with smaller total vessel and lumen areas, and an increased prevalence of lipid-rich necrotic core. Carotid calcification was related to CAD status in both males and females. Carotid CMR identifies distinct morphological and compositional differences in the carotid arteries between individuals with and without angiographically-defined obstructive CAD.Carotid Atherosclerosis (MRI) Progression Study (CAMPS, HL076378) and Cardiovascular Research Training Program (T-32, HL07838); and the General Clinical Research Center at the Wake Forest University School of Medicine (M01 RR-07122)

Laboratory-Evolved Mutants of an Exogenous Global Regulator, IrrE from Deinococcus radiodurans, Enhance Stress Tolerances of Escherichia coli

The tolerance of cells toward different stresses is very important for industrial strains of microbes, but difficult to improve by the manipulation of single genes. Traditional methods for enhancing cellular tolerances are inefficient and time-consuming. Recently, approaches employing global transcriptional or translational engineering methods have been increasingly explored. We found that an exogenous global regulator, irrE from an extremely radiation-resistant bacterium, Deinococcus radiodurans, has the potential to act as a global regulator in Escherichia coli, and that laboratory-evolution might be applied to alter this regulator to elicit different phenotypes for E. coli.To extend the methodology for strain improvement and to obtain higher tolerances toward different stresses, we here describe an approach of engineering irrE gene in E. coli. An irrE library was constructed by randomly mutating the gene, and this library was then selected for tolerance to ethanol, butanol and acetate stresses. Several mutants showing significant tolerances were obtained and characterized. The tolerances of E. coli cells containing these mutants were enhanced 2 to 50-fold, based on cell growth tests using different concentrations of alcohols or acetate, and enhanced 10 to 100-fold based on ethanol or butanol shock experiments. Intracellular reactive oxygen species (ROS) assays showed that intracellular ROS levels were sharply reduced for cells containing the irrE mutants. Sequence analysis of the mutants revealed that the mutations distribute cross all three domains of the protein.To our knowledge, this is the first time that an exogenous global regulator has been artificially evolved to suit its new host. The successes suggest the possibility of improving tolerances of industrial strains by introducing and engineering exogenous global regulators, such as those from extremophiles. This new approach can be applied alone or in combination with other global methods, such as global transcriptional machinery engineering (gTME) for strain improvements

Molecular Epidemiology and Evolution of Human Enterovirus Serotype 68 in Thailand, 2006–2011

BACKGROUND: Publications worldwide have reported on the re-occurrence of human enterovirus 68 (EV68), a rarely detected pathogen usually causing respiratory illness. However, epidemiological data regarding this virus in particular on the Asian continent has so far been limited. METHODOLOGY/FINDINGS: We investigated the epidemiology and genetic variability of EV68 infection among Thai children with respiratory illnesses from 2006-2011 (n = 1810). Semi-nested PCR using primer sets for amplification of the 5'-untranslated region through VP2 was performed for rhino-enterovirus detection. Altogether, 25 cases were confirmed as EV68 infection indicating a prevalence of 1.4% in the entire study population. Interestingly, the majority of samples were children aged >5 years (64%). Also, co-infection with other viruses was found in 28%, while pandemic H1N1 influenza/2009 virus was the most common co-infection. Of EV68-positive patients, 36% required hospitalizations with the common clinical presentations of fever, cough, dyspnea, and wheezing. The present study has shown that EV68 was extremely rare until 2009 (0.9%). An increasing annual prevalence was found in 2010 (1.6%) with the highest detection frequency in 2011 (4.3%). Based on analysis of the VP1 gene, the evolutionary rate of EV68 was estimated at 4.93 × 10(-3) substitutions/site/year. Major bifurcation of the currently circulating EV68 strains occurred 66 years ago (1945.31 with (1925.95-1960.46)95% HPD). Among the current lineages, 3 clusters of EV68 were categorized based on the different molecular signatures in the BC and DE loops of VP1 combined with high posterior probability values. Each cluster has branched off from their common ancestor at least 36 years ago (1975.78 with (1946.13-1984.97)95% HPD). CONCLUSION: Differences in epidemiological characteristic and seasonal profile of EV68 have been found in this study. Results from Bayesian phylogenetic investigations also revealed that EV68 should be recognized as a genetically diverse virus with a substitution rate identical to that of enterovirus 71 genotype B (4.2 × 10(-3 )s/s/y)

Conjunctival Reconstruction with Progenitor Cell-Derived Autologous Epidermal Sheets in Rhesus Monkey

Severe ocular surface diseases are some of the most challenging problems that the clinician faces today. Conventional management is generally unsatisfactory, and the long-term ocular consequences of these conditions are devastating. It is significantly important to find a substitute for conjunctival epithelial cells. This study was to explore the possibility of progenitor cell-derived epidermal sheets on denuded amniotic membrane to reconstruct ocular surface of conjunctiva damaged monkeys. We isolated epidermal progenitor cells of rhesus monkeys by type IV collagen adhesion, and then expanded progenitor cell-derived epidermal sheets on denuded amniotic membrane ex vivo. At 3 weeks after the conjunctiva injury, the damaged ocular surface of four monkeys was surgically reconstructed by transplanting the autologous cultivated epidermal progenitor cells. At 2 weeks after surgery, transplants were removed and examined with Hematoxylin-eosin staining, Periodic acid Schiff staining, immunofluorescent staining, scanning and transmission electron microscopy. Histological examination of transplanted sheets revealed that the cell sheets were healthy alive, adhered well to the denuded amniotic membrane, and had several layers of epithelial cells. Electron microscopy showed that the epithelial cells were very similar in appearance to those of normal conjunctival epithelium, even without goblet cell detected. Epithelial cells of transplants had numerous desmosomal junctions and were attached to the amniotic membrane with hemidesmosomes. Immunohistochemistry confirmed the presence of the conjunctival specific markers, mucin 4 and keratin 4, in the transplanted epidermal progenitor cells. In conclusion, our present study successfully reconstructed conjunctiva with autologous transplantation of progenitor cell-derived epidermal sheets on denuded AM in conjunctival damaged monkeys, which is the first step toward assessing the use of autologous transplantation of progenitor cells of nonocular surface origin. Epidermal progenitor cells could be provided as a new substitute for conjunctival epithelial cells to overcome the problems of autologous conjunctiva shortage

YangZheng XiaoJi exerts anti-tumour growth effects by antagonising the effects of HGF and its receptor, cMET, in human lung cancer cells

BACKGROUND: Hepatocyte growth factor (HGF) is a cytokine that has a profound effect on cancer cells by stimulating migration and invasion and acting as an angiogenic factor. In lung cancer, the factor also plays a pivotal role and is linked to a poor outcome in patients. In particular, HGF is known to work in combination with EGF on lung cancer cells. In the present study, we investigated the effect of a traditional Chinese medicine reported in cancer therapies, namely YangZheng XiaoJi (YZXJ) on lung cancer and on HGF mediated migration and invasion of lung cancer cells. METHODS: Human lung cancer cells, SKMES1 and A549 were used in the study. An extract from the medicine was used. Cell migration was investigated using the EVOS and by ECIS. Cell–matrix adhesion and in vitro invasion were assessed. In vivo growth of lung cancer was tested using an in vivo xenograft tumour model and activation of the HGF receptor in lung tumours by an immunofluorescence method. RESULTS: Both lung cancer cells increased their migration in response to HGF and responded to YZXJ by reducing their speed of migration. YZXJ markedly reduced the migration and in vitro invasiveness induced by HGF. It worked synergistically with PHA665752 and SU11274, HGF receptor inhibitors on the lung cancer cells both on HGF receptor activation and on cell functions. A combination of HGF and EGF resulted in a greater increase in cell migration, which was similarly inhibited by YZXJ, and in combination with the HGF receptor and EGF receptor inhibitors. In vivo, YZXJ reduced the rate of tumour growth and potentiated the effects of PHA665752 on tumour growth. It was further revealed that YZXJ significantly reduced the degree of phosphorylation of the HGF receptor in lung tumours. CONCLUSION: YZXJ has a significant role in reducing the migration, invasion and in vivo tumour growth of lung cancer and acts to inhibit the migratory and invasive effects induced by HGF and indeed by HGF/EGF. This effect is likely attributed to the inhibition of the HGF receptor activation. These results indicate that YZXJ has a therapeutic role in lung cancer and that combined strategy with methods to block HGF and EGF should be considered. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12967-015-0639-1) contains supplementary material, which is available to authorized users