Broad-Spectrum Antiviral Activity of RNA Interference against Four Genotypes of Japanese Encephalitis Virus Based on Single MicroRNA Polycistrons

Japanese encephalitis virus (JEV), a neurotropic mosquito-borne flavivirus, causes acute viral encephalitis and neurologic disease with a high fatality rate in humans and a range of animals. Small interfering RNA (siRNA) is a powerful antiviral agent able to inhibit JEV replication. However, the high rate of genetic variability between JEV strains (of four confirmed genotypes, genotypes I, II, III and IV) hampers the broad-spectrum application of siRNAs, and mutations within the targeted sequences could facilitate JEV escape from RNA interference (RNAi)-mediated antiviral therapy. To improve the broad-spectrum application of siRNAs and prevent the generation of escape mutants, multiple siRNAs targeting conserved viral sequences need to be combined. In this study, using a siRNA expression vector based on the miR-155 backbone and promoted by RNA polymerase II, we initially identified nine siRNAs targeting highly conserved regions of seven JEV genes among strains of the four genotypes of JEV to effectively block the replication of the JEV vaccine strain SA14-14-2. Then, we constructed single microRNA-like polycistrons to simultaneously express these effective siRNAs under a single RNA polymerase II promoter. Finally, these single siRNAs or multiple siRNAs from the microRNA-like polycistrons showed effective anti-virus activity in genotype I and genotype III JEV wild type strains, which are the predominant genotypes of JEV in mainland China. The anti-JEV effect of these microRNA-like polycistrons was also predicted in other genotypes of JEV (genotypes II and IV), The inhibitory efficacy indicated that siRNAs×9 could theoretically inhibit the replication of JEV genotypes II and IV

Prevalence of chronic kidney disease in population-based studies: Systematic review

which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background: Chronic kidney disease (CKD) is becoming a major public health problem worldwide. This article reviews the published evidence of prevalence of CKD in population-based study samples that used the standardized definition from the Kidney Disease Outcomes Quality Initiative of the National Kidney Foundation (K/DOQI) practice guideline, and particularly focus on performance of serum-creatinine based equations for GFR estimation. We provide a summary of available data about the burden of CKD in various populations. Methods: We performed a systematic review of available published data in MEDLINE. A combination of various keywords relevant to CKD was used in this research. Related data of included studies were extracted in a systematic way. Results: A total of 26 studies were included in this review. The studies were conducted in different populations, and the number of study participants ranged from 237 to 65181. The median prevalence of CKD was 7.2 % in persons aged 30 years or older. In persons aged 64 years or older prevalence of CKD varied from 23.4 % to 35.8%. Importantly, the prevalence of CKD strongl

Voluntary heart rate reduction following yoga using different strategies

Background/Aims: One month of yoga training has been shown to reduce the pulse rate voluntarily without using external cues. Hence, the present study was designed to understand the strategies used by yoga practitioners and autonomic changes associated with voluntary heart rate reduction. Materials and Methods: Fifty volunteers (group mean age ± S.D., 25.4 ± 4.8 years; 25 males) were assessed in two trials on separate days. Each trial was for 12 minutes, with a ′pre′ state and ′during′ state of 6 minutes each. For both trials the ′pre′ state was relaxation with eyes closed. In the ′during′ state of Trial I, subjects were asked to voluntarily reduce their heart rate using a strategy of their choice. From their responses to specific questions it was determined that 22 out of 50 persons used breath regulation as a strategy. Hence, in the ′during′ state of Trial II, subjects were asked to voluntarily reduce their heart rate by breath regulation. Results: In the first trial, the heart rate was reduced by an average of 19.6 beats per minute and in the second trial (with breath regulation exclusively) an average decrease of 22.2 beats per minute was achieved. Conclusions: Hence, the strategy used did not markedly alter the outcome

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Not AvailableSix different isolates of Sclerotinia sclerotiorum were isolated from vegetable host crops namely brinjal, cauliflower, French bean, and pea on potato dextrose agar. These isolates were subjected for morphological characterization, cross infectivity/pathogenicity test and chemo-sensitivity towards bioagent and new molecules of fungicides. On the basis of morphological characteristics viz., colony colour and texture, the tested isolates were categorized into two groups. Cross infectivity / pathogenicity test were performed on French bean, dolichos bean and pea using leaf detachment technique. Results on cross infectivity revealed non-host specificity of tested isolates of the pathogen. As regards to chemo- sensitivity of these isolates with tebuconazole 250 EC, azoxystrobin 23 SC, fluopyram 17.7+ tebuconazole 17.7 SC, Fluopicolide 6.25 %+Propamocarb Hydrochloride 62.5% SC at concentration of 250, 500, 1000 and 1500 ppm, the combination fungicide fluopyram 17.7+ tebuconazole 17.7 SC was found most effective at concentration of 250 ppm against tested isolates of S. sclerotiorum. In case of in vitro evaluation of bioagent, Trichoderma asperellum against these isolates, the highest mycelial growth inhibition (50.46%) against pea isolate (PSS- 1) and the lowest inhibition (26.15%) in case of French bean isolate (BSS-1) was observed. Cross infectivity and chemo sensitivity of the pathogen clearly indicate the emergence of this pathogen as broad spectrum covering wide host range.Not Availabl

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Not AvailableSix different isolates of Sclerotinia sclerotiorum were isolated from vegetable host crops namely brinjal, cauliflower, French bean, and pea on potato dextrose agar. These isolates were subjected for morphological characterization, cross infectivity/pathogenicity test and chemo-sensitivity towards bioagent and new molecules of fungicides. On the basis of morphological characteristics viz., colony colour and texture, the tested isolates were categorized into two groups. Cross infectivity/pathogenicitytest wereperformedon French bean, dolichos bean and pea using leaf detachment technique. Results on cross infectivity revealed non-host specificity of tested isolates of the pathogen. As regards to chemo-sensitivity of these isolates with tebuconazole 250 EC, azoxystrobin 23 SC, fluopyram 17.7+ tebuconazole 17.7 SC, Fluopicolide 6.25%+Propamocarb Hydrochloride 62.5% SC at concentration of 250, 500, 1000 and …Not Availabl

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Not AvailableNew Delhi metallo-β-lactamase-1 (NDM-1) is the major contributor to the emergence of carbapenem resistance in Gram-negative pathogens (GNPs) and has caused many clinically available β-lactam antibiotics to become obsolete. A clinically approved inhibitor of metallo-β-lactamase (MBL) that could restore the activity of carbapenems against resistant GNPs has not yet been found, making NDM-1 a serious threat to human health. Here, we have rationally developed an inhibitor for the NDM-1 enzyme, which has the ability to penetrate the outer membrane of GNPs and inactivate the enzyme by depleting the metal ion (Zn2+) from the active site. The inhibitor reinstated the activity of meropenem against NDM-1 producing clinical isolates of GNPs like Klebsiella pneumoniae and Escherichia coli. Further, the inhibitor efficiently restored meropenem activity against NDM-1 producing K. pneumoniae in a murine sepsis infection model. These findings demonstrate that a combination of the present inhibitor and meropenem has high potential to be translated clinically to combat carbapenem-resistant GNPs.Not Availabl

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Not AvailableInfections caused by drug-resistant Gram-negative pathogens continue to be significant contributors to human morbidity. The recent advent of New Delhi metallo-β-lactamase-1 (blaNDM-1) producing pathogens, against which few drugs remain active, has aggravated the problem even further. This paper shows that aryl-alkyl-lysines, membrane-active small molecules, are effective in treating infections caused by Gram-negative pathogens. One of the compounds of the study was effective in killing planktonic cells as well as dispersing biofilms of Gram-negative pathogens. The compound was extremely effective in disrupting preformed biofilms and did not select resistant bacteria in multiple passages. The compound retained activity in different physiological conditions and did not induce any toxic effect in female Balb/c mice until concentrations of 17.5 mg/kg. In a murine model of Acinetobacter baumannii burn infection, the compound was able to bring the bacterial burden down significantly upon topical application for 7 days.Not Availabl

Novel rhodanines with anticancer activity: design, synthesis and CoMSIA study

Three different series of some novel N-substituted rhodanines were designed for anticancer activity and prepared from the corresponding dithiocarbamates. The synthesized compounds were analyzed by IR, NMR and MASS to confirm their structures. All the titled compounds were found to be of Z configuration based on NMR spectral analysis. All the synthesized rhodanines were screened for in vitro anticancer activity against MCF-7 breast cancer cells at the concentration of 10 mu g. The compounds showed moderate to significant cytotoxicity. Amongst them, interestingly, compounds 10, 22 and 33 with cinnamoyl substitution at the 5th position of the thiazolidine ring system showed significant activity. Further, we subjected all these compounds to a CoMSIA study to study their 3D quantitative structure activity relationships (3D QSAR). The illustration about the design of novel rhodanines, synthesis, analysis, activity against MCF-7 cells and SAR via CoMSIA study are reported here