Search

While a large wealth of literature on aging pertains to in silico, experimental, and predicted genes, many of those genes do not have validated phenotypic consequences in human. Online Mendelian Inheritance in Man (OMIM) provides an exceptional compendium of authoritative, validated aging genes and phenotypes, the interactions among which may enhance the overall perspective of aging mechanisms in human.Here, we reviewed and investigated the global clustering pattern of the OMIM-indexed aging genes (until April 2021) in the gene co-expression and physical interaction networks, using the two keywords "aging" and "ageing". To allow for validity check, we randomly selected six sets of genes from the human genome as control genes, each set consisting of a similar number of genes obtained from the OMIM search. STRING was implemented in the weighted setting and using the edge betweenness parameter, to construct the integrated and tissue-specific networks of the age-related and control genes.286 aging (ageing) genes and a wide spectrum of 96 associated phenotypes were detected, including late-onset neurodegenerative disorders, cancers, osteoarthritis, and longevity. Despite the general terms used and the vast range of age-related phenotypes, we detected single clustering of the OMIM-extracted aging (ageing) genes in each of the integrated weighted co-expression and physical interaction networks (p0.0005), as opposed to multiple clustering of the control genes (p≥0.04). TP53 was the overlapping hub gene in each of the networks. Three genes, TP53, APP, and SIRT1 were the consistent hub genes co-expressed across eleven selected human tissues frequently affected by age-related phenotypes.We propose predominant single clustering of the human phenotype-associated aging genes in the co-expression and physical interaction networks, and list the top pathways and genes involved.

Non-Steroid-Anti-Inflammatory-Drugs (NSAIDs) are the main focal points of linkage between inflammation and cancer. These compounds affect the catalytic conversion of Arachidonic Acid to the main molecules of prostaglandin family. These exchanges are catalyzed by CycloOxygenase isozymes called COX I & II which are constitutive proteins in important organs like liver or kidney and inducible one in inflamed tissues or tumors, respectively. This study discusses on a new mechanistic approach through discovery of 4th generation of NSAIDs. Here utilizing combinations of online databases including DRUG BANK and PUBCHEM in conjunction with computational algorithms like Fast Flexible Docking as in FLEXX software followed by applying new filtering processes including extraction of structural descriptors by means of PASS software. Also, correlation between docking scores and bioactivities were analyzed by SPSS software. However, important molecular substructures were analyzed with Library MCS software for detailed constructional engineering of the compounds. All molecules and substructures were searched for their potential anti inflammatory activity in databases and searching engines such as ISI, GOOGLE and etc. Consequently, new drug candidates were appeared in novel resources in order to synthesize, buy or extract for future in vitro assays.