Human Parechovirus Genotypes -10, -13 and -15 in Pakistani Children with Acute Dehydrating Gastroenteritis

Human parechoviruses are known to cause asymptomatic to severe clinical illness predominantly respiratory and gastroenetric infections. Despite their global prevalence, epidemiological studies have not been performed in Pakistan. In this study, we retrospectively analyzed 110 fecal specimen and found 26 (24%) positive for viral RNA with HPeV-10 (n = 3, 23%), HPeV-13 (n = 4, 31%) and HPeV-15 (n = 6, 46%) genotypes. Clinical features of patients with different HPeV genotypes were compared. All HPeV positive children were aged ≤4 years (mean 13.92 months). The male-to-female ratio was 1: 1.17 (46.2 vs 53.8%) with significant association (p = .031) to HPeV infectivity. HPeV-10 and -13 were found during summer while HPeV-15 was only detected during late winter season. Disease symptoms were more severe in children infected with HPeV-10 and -13 as compared to HPeV-15. Fever and vomiting were observed in 100% cases of HPeV-10 and -13 while only 17% patients of HPeV-15 had these complaints. Phylogenetic analyses showed that HPeV-10, -13 and -15 strains found in this study have 9–13%, 16.8% and 21.8% nucleotide divergence respectively from the prototype strains and were clustered to distinct genetic lineages. This is the first report of HPeV-15 infection in humans although first identified in rhesus macaques. The arginine-glycine-aspartic acid (RGD) motif present at the C-terminal of VP1 responsible for the viral attachment to cellular integrins was not found in all of these strains. In conclusion, these findings enhance our knowledge related to the epidemiology and genetic diversity of the HPeV in Pakistan and support the need for continued laboratory based surveillance programs especially in infants and neonatal clinical settings. Further, the parechovirus pathogenesis, cross-species transmission and disease reservoirs must be ascertained to adopt better prevention measures.     

A combined approach to data mining of textual and structured data to identify cancer-related targets

Background  

We present an effective, rapid, systematic data mining approach for identifying genes or proteins related to a particular interest. A selected combination of programs exploring PubMed abstracts, universal gene/protein databases (UniProt, InterPro, NCBI Entrez), and state-of-the-art pathway knowledge bases (LSGraph and Ingenuity Pathway Analysis) was assembled to distinguish enzymes with hydrolytic activities that are expressed in the extracellular space of cancer cells. Proteins were identified with respect to six types of cancer occurring in the prostate, breast, lung, colon, ovary, and pancreas.     

Acanthocephala from lake fishes in Wisconsin: ecology and host relationships of Pomphorhynchus bulbocolli (Pomphorhynchidae)

Pomphorhynchus bulbocolli Linkins in Van Cleave, 1919, was considerably more common in fishes of the river-connected Tichigan Lake than of the landlocked Silver Lake, southeastern Wisconsin. It is reported from 17 species of principal, accessory, and occasional definitive hosts (new record in Moxostoma carinatum) and from 13 species of paratenic hosts (new records in Amia calva, Ictalurus punctatus, Lepomis cyanellus, and Pomoxis nigromaculatus). Infection patterns were influenced by fish species, feeding behavior, temperature, availability of intermediate host, type of water body, fish movement, and changes in fish host community. Host roles are not fixed but are often interchangeable. A seasonal cycle in prevalence, intensity, and maturation was evident, with greatest abundance and maturation during summer and recruitment during summer and autumn. Recruitment of new infections, development, and release of eggs, however, occurred all year. Sex ratio changed from near equal in new infections to one more highly in favor of females in older adults. Female fish were considerably more frequently and heavily infected than males. No relationship with fish age (size) was evident. Worms were mostly attached in posterior intestinal locations but initial establishment sites correlated with temperature. Translocation of P. bulbocolli due to competitive exclusion in concurrent infections was not observed. The significance of extraintestinal larval forms in the cycle of transmission was noted.     

Effect of neohesperidin dihydrochalcone on the activity and stability of alpha‐amylase: a comparative study on bacterial,fungal, and mammalian enzymes

Neohesperidin dihydrochalcone (NHDC) was recently introduced as an activator of mammalian alpha‐amylase. In the current study, the effect of NHDC has been investigated on bacterial and fungal alpha‐amylases. Enzyme assays and kinetic analysis demonstrated the capability of NHDC to significantly activate both tested alpha‐amylases. The ligand activation pattern was found to be more similar between the fungal and mammalian enzyme in comparison with the bacterial one. Further, thermostability experiments indicated a stability increase in the presence of NHDC for the bacterial enzyme. In silico (docking) test locates a putative binding site for NHDC on alpha‐amylase surface in domain B. This domain shows differences in various alpha‐amylase types, and the different behavior of the ligand toward the studied enzymes may be attributed to this fact. Copyright © 2015 John Wiley & Sons, Ltd.     

Slow Regulated Release of H2S Inhibits Oxidative Stress Induced Cell Death by Influencing Certain Key Signaling Molecules

Hydrogen sulphide (H₂S) is one of three gaseous signaling molecules after nitric oxide and carbon monoxide. Various H₂S donor compounds have been synthesized to study its physiological function. Among these compounds sodium hydrosulphide (NaHS), a donor of releasing H₂S rapidly have shown to be protective in certain neuronal cell line but several in vivo studies have generated conflicting data. Furthermore several slow releasing H₂S donors have been shown to have positive effects on cells in culture. The intracellular concentration of H₂S and hence its rate of production may be a factor in keeping the balance between its neuroprotective and toxic effects. The present study was undertaken to deduce how a rapid releasing H₂S donor (NaHS) as opposed to a slow releasing donor (ADTOH), affect oxidative stress related intracellular components and survival of RGC-5 cells. It was concluded that when RGC-5 cells are exposed to the toxic effects of glutamate in combination with buthionine sulfoxime (Glu/BSO), ADTOH was more efficacious in inhibiting apoptosis, scavenging reactive oxygen species (ROS), stimulation of glutathione (GSH) and gluthathione-S-transferase (GST). Western blot and qPCR analysis showed ADTOH increased the levels of Nrf2, HO-1, PKCα, p-Akt, Bcl-2 and XIAP but caused a decrease of Nfκβ and xCT greater than NaHS. This study is first to compare the efficacy of two H₂S donor drugs as potential neuroprotectants and demonstrate that slow regulated release of H₂S to cell culture can be more beneficial in inhibiting oxidative stress induced cell death.     

Evaluating the physiological effect of strobilurin-based fungicide (Opera 183 g/L SE) against Sclerotium rolfsii and Aspergillus niger pathogens of Arachis hypogaea L.

Abstract

The present study was designed to investigate the effect of fungicide Opera 183?g/L SE on groundnut crop (either as seed or foliar treatment) to control damages and losses incurred especially by the soil borne pathogens Sclerotium rolfsii and Aspergillus niger. The results revealed that 0.15% Opera-treated seeds showed early germination, high percentage of germination, less mortality rate in S. rolfsii and A. niger-infested soil. Enhanced activities of defence-related enzymes, protein, carbohydrate and chlorophyll content up to 2–4 d were observed in Opera-treated plants as compared with untreated plants. Moreover, the application of Opera had a positive effect on yield up to 22%, green fodder at the time of harvest and no disease incidence. From the present study, it is recommended that application of Opera at 750?ml/hectare in the form of foliar treatment to groundnut plants could help in inducing resistance towards opportunistic pathogens and also could enhance the yield.     

Reliable structural information for rational design of benzoxazole type potential cholesteryl ester transfer protein (CETP) inhibitors through multiple validated modeling techniques

Abstract

The drug design and discovery of lipid modulators is very demanding as no new molecule has entered into the market in the last 35 years. Cholesteryl ester transfer protein (CETP) is a promising target as lipid modulators. Inhibition of the CETP enzyme reduces the risk of cardiovascular events. The first CETP inhibitor torcetrapib and related drug candidates failed in the clinical trial due to the off-target effects leading to high toxicity. Thus, newer CETP inhibitors have now paramount importance to accelerate the drug discovery efforts in the field of cardiovascular disease (CVD). In the present study, 140 benzoxazole compounds were studied by using different chemometric techniques, for example, pharmacophore mapping, molecular docking, three-dimensional quantitative structure–activity relationship comparative molecular field analysis (3D-QSAR CoMFA), topomer CoMFA and Bayesian classification, in order to generate complete and reliable information regarding the structural requirements for the CETP inhibition. The best pharmacophore hypothesis was statistically significant (regression coefficient of 0.957 and a lower root mean square of 0.890). Molecular docking study revealed that cyano-substituted compounds form hydrogen bond with targeted macromolecule. The 3D-QSAR CoMFA model also produced a leave-one-out (LOO) cross-validated Q² of 0.527, an R² of 0.853 and an R²_Pred of 0.603. Similarly, two topomer CoMFA models were also statistically significant and reliable in terms of their Q², R² and R²_Pred values. The Bayesian classification study also provided the excellent ROC values of 0.919 and 0.939 for training and test sets, respectively. Overall, this study may help in the rational design of newer benzoxazole type compounds with higher CETP inhibition.

Communicated by Ramaswamy H. Sarma     

Synthesis, structural characterization and in vitro cytotoxicity and anti-bacterial activity of some copper(I) complexes with N,N′-disubstituted thioureas

A series of copper(I) complexes of N,N′-disubstituted thioureas, [C₆H₅CONHCSNHR]Cu(I)Cl where R = C₆H₅ (1a), 2-ClC₆H₄ (2a), 3-ClC₆H₄ (3a), 4-ClC₆H₄ (4a), 2,3-Cl₂C₆H₃ (5a), 2,4-Cl₂C₆H₃ (6a), 2,5-Cl₂C₆H₃ (7a), 2,6-Cl₂C₆H₃ (8a), 3,4-Cl₂C₆H₃ (9a) and 3,5-Cl₂C₆H₃ (10a) have been synthesized. These complexes (1a–10a) have been characterized by elemental analyses, IR, ¹H and ¹³C NMR spectroscopy, cyclic voltammetry and single crystal XRD for 1a and 8a, and for ligand 7. The X-ray crystal structures reveal that the complexes 1a and 8a are mononuclear in the solid state in which the copper atoms adopt a distorted tetrahedral geometry. In both the cases, the neutral N,N′-disubstituted thiourea ligands have been coordinated to the Cu(I) through the sulphur atom in a terminal mode. The complexes have been screened for their in vitro cytotoxic activity in human cell lines carcinomas A498 (Renal), EVSA-T (Breast), H226 (Lung), IGROV (Ovarian), M19 (Melanoma-Skin), MCF-7 (Breast) and WIDR (Colon). They show a moderate cytotoxicity against these seven human cancer cell lines comparable to that of the less active standard chemotherapeutic drugs used for comparison. They were also screened for their anti-bacterial activity and were found less active than the standard drug Imipenem.     

Lack of association between interleukin-13 gene polymorphisms (−1055 C/T and +2044 G/A) in Iranian patients with lung cancer

Lung cancer is one of the leading causes of death from cancer. Both immune cells and tumor cells play a key role in lung cancer immunity by secretion of cytokines and developing type-2 cell-mediated immune response. IL-13 is an immunoregulatory cytokine affecting tumor immunosurveillance by deviation of immune response from Th1 to Th2. In the present study we sought to determine the association of single nucleotide polymorphisms (SNPs) of IL-13 gene at positions +2044 (G/A) and −1055 (C/T) and lung cancer. One hundred forty one patients and 113 controls were recruited; control group was subdivided into smoker and nonsmoker individuals for serum detection. Genotyping was carried out by PCR-RFLP assay and IL-13 detection by ELISA method. No statistically significant difference was found in the frequency of genotypes, alleles, and haplotypes at positions +2044 (G/A) and −1055 (C/T) of IL-13 gene between lung cancer patients and controls. Serum level of IL-13 was not detectable in both groups. The results of this study reveal that although +2044 (G/A) and −1055 (C/T) SNPs in IL-13 are implicated in some pulmonary processes, they do not confer susceptibility to lung cancer in Iranian population.