Virtual screening of natural inhibitors targeting ornithine decarboxylase with pharmacophore scaffolding of DFMO and validation by molecular dynamics simulation studies.

Ornithine decarboxylase (ODC) is an enzyme that initiates polyamine synthesis in human. Polyamines play key roles in cell-cell adhesion, cell motility and cell cycle regulation. Higher synthesis of polyamines also occurs in rapidly proliferating cancer cells are mediated by ODC. As per earlier studies, di-flouro-methyl-orninthine (DFMO) is a proven efficient inhibitor ODC targeting the catalytic activity, however, its usage is limited due to side effects. Targeting ODC is considered as a potential therapeutic modality in the treatment of cancer. In this study, it is attempted to use DFMO scaffold to build a ligand-based pharmocophore query using MOE to screen similar active compounds from Universal Natural Products Database with better ADMET properties. The identified compounds were virtually screened against the active cavity of ODC using Glide. Further, potential natural hits targeting ODC were shortlisted based on Molecular Mechanics/Generalized-Born/Surface Area (MM-GBSA) score. Finally, molecular dynamics simulations were performed for the natural molecule hit and DFMO in complex with ODC using Desmond. Among the hits shortlisted, 2-amino-5, 9, 13, 17-tetramethyloctadeca-8, 16-diene-1, 3, 14-triol (UNPD208110) was found to be highly potential, as it showed a higher binding affinity in terms of interactions with key active cavity residues, and also showed better ADMET property, HUMO-LUMO gap energy and more stable complex formation with ODC compared to DFMO. Hence, the proposed molecule (UNPD208110) shall be favourably considered as a potential natural inhibitor targeting ODC-mediated disease conditions.

Ornithine and its role in metabolic diseases: An appraisal.

Ornithine is a non-essential amino acid produced as an intermediate molecule in urea cycle. It is a key substrate for the synthesis of proline, polyamines and citrulline. Ornithine also plays an important role in the regulation of several metabolic processes leading to diseases like hyperorithinemia, hyperammonemia, gyrate atrophy and cancer in humans. However, the mechanism of action behind the multi-faceted roles of ornithine is yet to be unraveled completely. Several types of cancers are also characterized by excessive polyamine synthesis from ornithine by different rate limiting enzymes. Hence, in this review we aim to provide extensive insights on potential roles of ornithine in many of the disease related cellular processes and also on the structural features of ornithine interacting proteins, enabling development of therapeutic modalities.

Unraveling genomic and phenotypic nature of multidrug-resistant (MDR) Pseudomonas aeruginosa VRFPA04 isolated from keratitis patient.

Multidrug-resistant (MDR) Pseudomonas aeruginosa VRFPA04, obtained from a keratitis patient was found to exhibit resistance to betalactam (Penicillins, cephalosporins, including carbapenems, except aztreonam), aminoglycosides, quinolone group of drugs and susceptible to colistin. The complete genome sequencing of the ocular isolate to measure and ascertain the degree of multidrug resistance in VRFPA04 strain resulted in 6,818,030bp (6.8Mb) genome sizes, which happen to be the third largest genome available in the Genbank to date. Two chromosomally integrated class I integrons carrying blaVIM-2 carbapenemase gene, multiple secretory systems consisting of types I-VI and VIII proteins and ocular virulence factors exo-T, Y, U and exotoxin A, a gene that inhibits protein synthesis which could have caused corneal cell death and Phytohormone auxin biosynthetic protein were detected in the genome of VRFPA04 Genome. In addition, 58 Regions of Genomic Plasticity (RGPs) regions, multiple phage genomes, genomic islands, CRISPR genes and RND family efflux pumps, such as MexCD-OprJ and MexEF-OprN and its regulators, MexT and MexR, were unraveled in VRFPA04. Thus, the current study reveals the virulence factors and resistome nature of an ocular isolate P aeruginosa VRFPA04 genome.

Knowledge, Attitude and Practices of Parents Regarding Primary Teeth Care of their Children in Davangere city, India

Objetivo: Avaliar o conhecimento, atitudes e práticas de pais da cidade de Davangere, Índia, a respeito do cuidado com osdentes decíduos de seus filhos. Método: Mil questionários contendo aproximadamente 10 perguntas em dois idiomas Inglês e em dialeto local) foram distribuídos aos pais da cidade de Davangere, Índia. As respostas foram tabuladas e os resultados expressos por meioda distribuição de freqüência (absoluta e percentual). Resultados: A maioria dos pais não tinham consciência da importância dos dentes decíduos. Apenas 4% dos entrevistados tinham conhecimento sobre os dentes decíduos. Quando perguntados sobre a importância dos dentes decíduos, 82%dos pais disseram que esses elementos dentários não são importantes. Quanto à freqüência de escovação, a maioria(91,1%) dos pais relatou que eles solicitavam que os seus filhos escovassem os dentes uma única vez ao dia. Noventa vírgula seis por cento dos pais afirmaram que escolheriam os pediatras dos seus filhos. Apesar de trazerem os filhos ao cirurgião-dentista regularmente para consultas de rotina, muitos preferem não restaurá-los, mas deixá-los como estão (32%) e até mesmo extraí-los (61%).Conclusão: Verifica-se uma falta de conhecimento entre amaioria dos pais de Davangere, relativas aos cuidados com a dentição decídua de seus filhos. Deste modo, um alto nível deconsciência era obviamente desejável entre esses pais.

Objective: To assess the knowledge, attitude and practices of parents of Davangere city regarding the care of primary teeth. Methods: 1000 questionnaires containing about 10 questions written both in English and local language (Kannada) were prepared for data collection and were personally distributed to 1000 parents of Davangere city. Reponses obtained were tabulated and the results of the questionnaire were expressed as frequency distribution and computed in percentages. Results: Most of the parents were unaware of the importance of the primary teeth. Only 4% of parents had knowledge about primary teeth. When questioned about the importance of primary teeth, 82% of parents told that primary teeth are not important. For frequency of brushing, majority (91.1%) of parents reported that only once they ask their children to brush in a day. 90.6% parents stated that they would choose their child's paediatricians. Despite bringing their children to the dentist on a regular basis for check-ups, many would prefer not to have these teeth filled but would rather that they were left (32%) or even extracted (61%). Conclusion: There is a lack of knowledge in majority of parents of Davangere, pertaining to primary teeth care of their children. Thus, a high level of awareness was obviously desirable among these parents.