Evaluation of wound healing active principles in the transdermal patch formulated with crude bio wastes and plant extracts against GSK-3 beta - an in silico study.

The wound-healing process is accelerated by inhibiting proteins that decelerate the wound-healing pathway. One of the active proteins involved in enhancing healing at the nuclear level and in gene expression is catenin. Inhibition of Glycogen Synthase Kinase 3ß (GSK3 ß) phosphorylates and degrades catenin via the downstream Wnt signalling pathway, thereby stabilizing catenin. A medicated wound dressing transdermal patch designed with fusion of bio wastes, viz. physiologically clotted fibrin, fish scale collagen, and the ethanolic extract of Mangifera indica (L.) and spider web, was analysed against GSK3ß to enhance healing. In our earlier studies, the compounds present in the transdermal patch were identified using GC-MS analysis; 12 compounds exhibiting the wound healing mechanism were analyzed using PASS software and filtered out. From these 12 compounds, 6 compounds that possessed drug-likeness were screened by SwissADME and vNN-ADMET to dock against GSK3ß in the present work. The PyRx results confirmed the binding of the six ligands to the active site of the target protein. Though the remaining filtered ligands also exhibited inhibitory activity, Molecular dynamics simulation studies were carried out with 100 ns on a complex of 10,12 Tricosadiyonic acid, Nopyl acetate and 2 Methyl 4 Heptanol as they showed binding affinity of -6.2Kcal/mol, -5.7Kcal/mol and -5.1Kcal/mol respectively. The stability of the complex was validated using MD simulation parameters RMSD, RMSF, Rg, and Number of Hydrogen bonds. These results implied that the transdermal patch would be efficient in accelerating the wound healing process through the inactivation of GSK3ß.Communicated by Ramaswamy H. Sarma.

Screening of Atherosclerotic Druggable Targets from the Proteome Network of Differentially Expressed Genes.

Differently expressed genes of atherosclerotic sample analysis are helpful to sort the prominent genes that influence the plaque formation and progression. Scientific evidence-based protein-protein interaction network (PPIN) studies were used to find hub proteins in complex disease conditions. Druggable capacity is one of the important parameters to confirm as a successful drug target. Construction of protein interaction network and principal node analysis (PNA) on atherosclerotic data sets lead to screen the hub proteins. Furthermore, druggable property of protein pocket confirms the targetability of susceptible target candidates and for target selection. Differentially expressed genes are identified through GEO2R analyzer on data sets of various atherosclerotic samples. STRING database and Cytoscape are employed to construct PPIN. Targets were identified by PNA such as centrality measures and clustering algorithm. Gene Ontology enrichment also used as one of the screening parameters to filter the candidates related to atherosclerotic terms. Topological evaluation of target protein was successfully done by ITASSER and GROMACS, respectively. Grid-based principle of DoGSiteScorer is utilized for druggability analysis. Six proteins such as integrin alpha L (ITGAL), metallothionein 1F (MT1F), metallothionein 1X (MT1X), P-selectin glycoprotein ligand-1 (SELPLG), solute carrier family 30 A, zinc transporter protein (SLC30A1), and TNFSF13B are screened as potential biomarkers through network-based analysis. Among the six, ITGAL, SELPLG, SLC30A1, and TNSF13B are identified as better prioritized atherosclerotic targets through druggability efficiency.

Protein Network Studies on PCOS Biomarkers With S100A8, Druggability Assessment, and RNA Aptamer Designing to Control Its Cyst Migration Effect.

The prevalence of polycystic ovary syndrome (PCOS) has been gradually increasing among adult females worldwide. Laparoscopy drilling on ovary is the only available temporary solution with a high incidence of reoccurrence. S100A8 with S100A9 complex is believed to facilitate the cyst migration in PCOS condition. The high evident protein interaction network studies between PCOS biomarkers, cancer invasion markers, and the interactors of S100A8 confirm that this protein has strong interaction with other selective PCOS biomarkers, which may be associative in the immature cyst invasion process. Through the network studies, intensive structural and pathway analysis, S100A8 is identified as a targetable protein. In this research, the non-SELEX in silico method is adapted to construct RNA Library based on the consensus DNA sequence of Glucocorticoid Response Element (GRE) and screened the best nucleotide fragments which are bound within the active sites of the target protein. Selected sequences are joined as a single strand and screened the one which competitively binds with minimal energy. In vitro follow-up of this computational research, the designed RNA aptamer was used to infect the MCF7 cell line through Lipofectamine 2000 mediated delivery to study the anti-cell migration effect. Wound Scratch assay confirms that the synthesized 18-mer oligo has significant inhibition activity toward tumor cell migration at the cellular level.

Report on biopharmaceutical profile of recent biotherapeutics and insilco docking studies on target bindings of known aptamer biotherapeutics.

Accumulated Toxicity, disease recurrence and drug resistivity problems have been observed due to the synthetic and semisynthetic therapeutic practices, which alternatively led to focus on Bio-therapeutics production than xenobiotics. Quick plasma clearance and high potency are the reasons for trending research with huge pharma market of numerous Bio-therapeutics than ever before. Researchers proved that most of the nano and micro Bio-therapeutics have multiple beneficial therapeutic effects. We have analyzed the past, and present scenario of some notable clinically approved Bio-therapeutics to identify the future formulation needs with advanced techniques. Protein-related drugs are the foremost Bio-therapeutics such as antibodies, enzymes, and short, fragmented polypeptides show aggregation properties during storage, naked peptide moieties are resisted by the polar cell membrane, and also the antidrug antibodies were reported. Even though Nucleic acid nano-bodies are excellent target binders than proteins, they had only a few minutes of half-life. Maintaining homogeneousness upon storage of Bio-therapeutics is still a significant challenge in industrial-scale formulation. Notably, plant systems are identified as most useful cost-effective hosts to produce human enzymes than animal systems without any possible viral loads. Irrespective of numerous advancements in routes of administration and additives, subcutaneous is still a golden one to achieve better dynamics. Additionally, the interactions and effective bonds made by each class of well-known aptamer biotherapeutics which are considered as future drugs were studied.