Study of human allergic milk whey protein from different mammalian species using computational method

Nowadays, safety and quality assessment of food used for human consumption have to consider by its possible contribution to the maintenance or improvement of the consumer''s health. Milk is an important food with many nutrients. Cow milk is an important source of energy, protein, vitamins and minerals for the growing child as well as adults. But, numerous cow milk proteins have been implicated in allergic responses and most of these have been shown to contain multiple allergic epitopes. The present study disclosed best alternatives to cow milk, which are not allergic and as good as cow milk in nutritional value. The in silico analysis of casein (alpha s1, alpha s2, beta and kappa) and beta-lactoglobulin, unveils that sheep milk is a more suitable alternate to cow milk for allergic infants and buffalo milk for allergic adult humans.     

Evaluation of Salmonella enterica Serovar Typhimurium TTSS-2 Deficient fur Mutant as Safe Live-Attenuated Vaccine Candidate for Immunocompromised Mice

Salmonella enterica serovar Typhimurium has been extensively exploited as live attenuated vaccines (LAV) which generally confers better protection than killed or subunit vaccines. However, many LAV are limited by their inherent ability to access systemic organs in many of the vaccinated hosts, especially those which are immunocompromised. We evaluated the efficacy of a live-attenuated SPI2-deficient (ΔssaV) S. Typhimurium vaccine candidate (MT13) that additionally devoids the ferric uptake regulator (fur). We used specific pathogen free (SPF) streptomycin-pretreated mouse colitis model that included healthy C57BL/6 and immunocompromised iNos ^−/−, IL10^−/− and CD40L^−/− in the background of C57BL/6 mice to assess the efficacy of developed vaccine candidate. In our study, the S. Typhimurium MT13 strain was established as a safe vaccine candidate to be administered in immunocompromised mice as it was found to be systemically attenuated without conferring significant pathological signs and growth defect within the host. In bacterial challenge experiment, the MT13-vaccinated C57BL/6 mice were protected from subsequent wild-type S. Typhimurium infection by inducing proficient mucosal immunity. The MT13 strain elicited efficient O-antigen specific mucosal secretory IgA associated protective response which was comparable with its parental ssaV mutant. Vaccination with MT13 also showed proficient T-cell activation in host mice; which has direct relation with pathogen clearance from host tissues. Collectively, these data implicate the possible application of SPI-2 deficient fur mutant (MT13) as a novel live attenuated vaccine strain with adept immunogenicity and improved safety, even in immunocompromised hosts. Further, this vaccine candidate can be employed to express heterologous antigens targeted against several other diseases, especially related to enterocolitic pathogens.     

Mitochondrial-derived free radicals mediate asbestos-induced alveolar epithelial cell apoptosis

Asbestos causes pulmonary toxicity by mechanisms that in part involve reactive oxygen species (ROS). However, the precise source of ROS is unclear. We showed that asbestos induces alveolar epithelial cell (AEC) apoptosis by a mitochondrial-regulated death pathway. To determine whether mitochondrial-derived ROS are necessary for causing asbestos-induced AEC apoptosis, we utilized A549-rho(omicron) cells that lack mitochondrial DNA and a functional electron transport. As expected, antimycin, which induces an oxidative stress by blocking mitochondrial electron transport at complex III, increased dichlorofluoroscein (DCF) fluorescence in A549 cells but not in A549-rho(omicron) cells. Compared with A549 cells, rho(omicron) cells have less asbestos-induced ROS production, as assessed by DCF fluorescence, and reductions in total glutathione levels as well as less caspase-9 activation and apoptosis, as assessed by TdT-mediated dUTP nick end labeling staining and DNA fragmentation. A mitochondrial anion channel inhibitor that prevents ROS release from the mitochondria to the cytoplasm also blocked asbestos-induced A549 cell caspase-9 activation and apoptosis. Finally, a role for nonmitochondrial-derived ROS with exposure to high levels of asbestos (50 microg/cm(2)) was suggested by our findings that an iron chelator (phytic acid or deferoxamine) or a free radical scavenger (sodium benzoate) provided additional protection against asbestos-induced caspase-9 activation and DNA fragmentation in rho(omicron) cells. We conclude that asbestos fibers affect mitochondrial DNA and functional electron transport, resulting in mitochondrial-derived ROS production that in turn mediates AEC apoptosis. Nonmitochondrial-associated ROS may also contribute to AEC apoptosis, particularly with high levels of asbestos exposure.     

Hydroxytriamides as potent gamma-secretase inhibitors

Using a cell-based assay, we have identified optimal residues and key recognition elements necessary for inhibition of gamma-secretase. An (S)-hydroxy group or 3,5-difluorophenylacetyl group at the amino terminus and N-methyltertiary amide moiety at the carboxy terminus provided potent gamma-secretase inhibitors with an IC(50) <10 nM.     

3-O-beta-D-Galactopyranoside of quercetin as an active principle from high altitude Podophyllum hexandrum and evaluation of its radioprotective properties

The aqueous-ethanolic extract (AEE) of high altitude Podophyllum hexandrum has earlier been reported to render a radioprotective effect against lethal gamma radiation in in vitro model. AEE has also been reported to possess metal chelating and DNA protecting properties. The present study was undertaken to isolate and characterize the bioactive principle present in AEE and investigate its role in radiation protection. A novel molecule was found to be present in AEE and was assigned as 3-O-beta-D-galactoside of quercetin by acid hydrolysis, LC-MS, LC-APCI-MS/MS and 13C NMR spectra. Various biological activities were investigated at in vitro level. The antioxidant potential of AEE in lipid and aqueous phase was determined against numerous stresses. AEE was found to be significantly (p < 0.05) protective, i.e., against Fe2+ and Cu2+-induced linoleic acid degradation, respectively. Radiation-induced lipid oxidation studies revealed that AEE maximally works at a [lignan]/0.25 kGy ratio 400 (ratio of concentration of AEE divided by the radiation dose, i.e., 0.25 kGy) and no drug-induced lipid oxidation at all concentrations tested was found. In a time-dependent study, total antioxidant activity was maximally exhibited at 1 mg/ml. The site-specific and non-site-specific deoxyribose degradation assay exhibited a dose-dependant hydroxyl scavenging potential of AEE (0.05-500 microg/ml). The anti-lipid peroxidation ability of AEE against radiation (0.25 kGy)-induced lipid peroxidation was higher in case of neural tissue homogenate as compared to kidney homogenate [activity ratio: 0.039 (brain) < 0.24 (kidney)]. The protein protection study using bovine serum albumin was also done for two time intervals (2 h and 4 h) and significant (p < 0.05) protection was observed at 500 microg/ml (> 97%). This study implies that 3-O-beta-D-galactoside present in AEE renders radioprotection by protecting lipids, proteins in renal and neural model system against supra-lethal (0.25 kGy) gamma radiation.     

Effect of antibiotics on growth and laccase production from Cyathus bulleri and Pycnoporus cinnabarinus

The effect of nine different antibiotics (chloramphenicol, ampicillin trihydrate, kanamycin A monosulfate, neomycin sulfate, erythromycin, thiostrepton, tetracycline, apramycin sulfate and streptomycin sulfate) on growth and laccase production from Cyathus bulleri and Pycnoporus cinnabarinus has been investigated. All the antibiotics tested at a concentration of 200 mg/l affected the fungal growth, release of protein and laccase production to different extent. Inhibition in fungal growth was found to be positively correlated with increase in laccase production. Interestingly, apramycin sulfate inhibited biomass production (14.9-26.2%), nevertheless, it stimulated maximum laccase production (18.2 U/ml) in both the fungi. Increasing concentrations of apramycin sulfate enhanced laccase production from P. cinnabarinus but not from C. bulleri.     

Studies on synthesis and evaluation of quantitative structure-activity relationship of 5-[(3'-chloro-4',4'-disubstituted-2-oxoazetidinyl)(N-nitro)amino]-6-hydroxy-3-alkyl/aryl[1,3]azaphospholo[1,5-a]pyridin-1-yl-phosphorus dichlorides

A new series of 5-[(3'-chloro-4',4'-disubstituted-2-oxoazetidinyl)(N-nitro)amino]-6-hydroxy-3-alkyl/aryl[1,3]azaphospholo[1,5-a]pyridin-1-yl-phosphorus dichlorides has been synthesized and subjected to acute antibacterial and antifungal screening studies. All the derivatives belonging to this series delineated remarkable activity as compared to standard drugs (ampicillin and clotrimazole). Compounds are quantitatively analyzed in relation to their different physicochemical parameters. Significant correlations were obtained between biological activity and polarizability parameter (MR).