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Acinetobacter baumannii is an emerging multi-drug resistant pathogen causing significant mortality in hospitalized ICU patients which demands developing new methods for prevention and treatment. A. baumannii 19606 proteome was analysed in silico through the online tool Vaxign for finding potential vaccine candidates. The selected nuclease (NucAb) was predicted to possess all the attributes of a promising vaccine candidate like outer membrane localization, high adhesin probability (0.53), one transmembrane helix only, non-homology to human proteins and presence of B-cell and T-cell epitopes binding with high affinity (percentile rank ≤ 1) to HLA alleles prevalent at high frequency in North Indian populations. nuc Ab gene was highly prevalent (100%) among the clinical isolates (40/40) and conserved (>98%) among NCBI sequenced Acinetobacter strains. It was cloned in pET28a, purified and its immunoprotective potential was validated in murine pneumonia model. Immunization of BALB/c mice with recombinant NucAb (25 μg) elicited high antibody titre (1–5 × 10 5 ) which reduced bacterial load by 5 log cycles in lungs of mice challenged with optimized lethal dose (10 8 CFU). Lung histopathology revealed marked suppression of inflammation. Pro-inflammatory cytokines (TNF-α and IL-6) levels were reduced significantly and anti-inflammatory (IL-10) cytokine increased in lungs and serum leading to decreased severity and slow progression of disease. Though active immunization showed low survival rate (20%), passive immunization improved the survival (40%). This is the first study reporting an outer membrane nuclease as a vaccine candidate in Gram negative bacterium, A. baumannii through reverse vaccinology approach. [ABSTRACT FROM AUTHOR]

Abstract: Prebiotics are substances that promote the growth of beneficial microorganisms thus, having health benefits as functional food. In the present study, comparative effect of prebiotics inulin and lactulose on 1,2-dimethylhydrazine dihydrochloride (DMH) induced procarcinogenic biomarkers in early colon carcinogenesis is described. It was found that aberrant crypt foci counts were significantly (p <0.05) less in both prebiotics+DMH treated group compared with DMH treated group, but percent reduction was maximum (p <0.05) in inulin+DMH treated group. The activity of β-glucuronidase and β-glucosidase decreased significantly (p <0.05) in animals belonging to inulin+DMH group compared with lactulose+DMH treated. The study suggests that prebiotic inulin may possess better prophylactic potential than lactulose due to reduced biomarkers of colon carcinogenesis in the initiation phase. [Copyright &y& Elsevier]

Abstract: The aim of this study was to investigate and characterize different crystal forms of arteether, a rapidly acting, highly potent antimalarial drug for the treatment of acute Plasmodium falciparum malaria. Six different crystal forms were prepared utilizing various polar and non-polar solvents. Scanning electron microscopy (SEM) revealed differences in the surface characteristics of the six forms from those of a commercial sample. Differential scanning calorimetry (DSC) revealed the absence of a desolvation endotherm indicating that the forms were neither hydrates nor solvates. Powder X-ray diffraction (PXRD) patterns of the forms showed much weaker major peaks than in the commercial sample indicating them to be less crystalline. Solubility and dissolution studies showed that the most amorphous form was the most soluble and possessed the highest antimalarial activity. [Copyright &y& Elsevier]

Abstract: Inclusion of artesunate in the cavity of β-cyclodextrin (β-CD) as well as its methyl and hydroxypropyl derivatives was investigated experimentally and by molecular modeling studies. The effect of PEG on the inclusion was also studied. A 1:1 stoichiometry was indicated by phase-solubility studies both in the presence and absence of PEG and suggested by the mass spectrometry. The mode of inclusion was supported by 2D NMR and results were further verified by docking studies utilizing Fast Rigid Exhaustive Docking acronym. The thermodynamic parameters were determined for both binary and ternary systems using solution calorimetry and were found to be best for the methyl-β-cyclodextrin (Me-β-CD) system. However, the presence of PEG improves the complexation ability as evident from elevation in the numerical value of the stability constant (K). Solubility and dissolution profile of binary complex is enhanced in the presence of PEG, which is approximately at par with drug Me-β-CD complexes. In vivo studies showed 100% survivability in artesunate–Me-β-CD complexes. [Copyright &y& Elsevier]