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STAT3 signaling is a major intrinsic pathway for cell proliferation owing to its frequent activation in injured tissues. Various STAT3-regulated genes encode cytokines and growth factors, the receptors of which in turn activate the same STAT3 pathways, thereby regulating cell proliferation. In present study, we aimed to analyze several compounds for their wound healing and tissue repair potential by computer-aided virtual screening and Molecular dynamics (MD) simulation. Based on literature studies, a total of 36 drug molecules were selected having critical functions in wound healing and tissue repair. The pharmacological features (ADME and toxicity) of these molecules were predicted to find lead molecules among them. Further, a comparative study was performed to screen binding efficiency of STAT3 with many conventional wound healers by molecular docking. Among all, W6S, Strychnin, Prednisone and N-(6-(4-(3-(4-((4-Methylpiperazin-1-yl) methyl)-3- (trifluoromethyl)phenyl)ureido)phenoxy)pyrimidin-4-yl)cyclopropanecarboxamide showed best docking with STAT3 protein. The calculated binding energy of these molecules with STAT3 was found to be -8.9 Kca/mol for N-(6-(4-(3-(4-((4-Methylpiperazin-1-yl) methyl)-3-(trifluoromethyl) phenyl)ureido)phenoxy)pyrimidin-4-yl)cyclopropanecarboxamide, -8.7 Kcal/mol for W6S, -8.5 Kcal/mol for Strychnine and -8.4 Kcal/mol for Prednisone . The result was reconsidered for MD simulation. The simulation result showed stable binding of the ligand with STAT3 protein for 100 ns. These compounds showed better interaction potential with STAT3 was compared to known tissue repair molecules. Our data paves way for further exploration of these molecules as novel cell proliferators to be tested in various types of wound and tissue injuries.Communicated by Ramaswamy H. Sarma.

Despite substantial progress in surgery, managing multi-tissue injuries is strenuous to accomplish and requires a multi-staged serial treatment of individual tissues. Stimulated regeneration affects the complete structural and functional repair of both hard and soft tissues post-injury and thus serves as an attractive therapeutic option to target multi-tissue injuries. This study utilized data mining and structural analysis to identify a target that has the ability to evoke healing of the two most commonly injured tissues i.e., bone and muscle, and stimulate the inherent vascular connectivity between the tissues. To find out the multipotential molecule the gene expression profile from GSE34747 was extracted and processed to identify the differentially expressed genes (DEGs). The DEGs were then subjected to gene ontology enrichment analysis to filter out a target that is likely to regulate the multi-tissue regeneration. Further, STITCH and PubChem databases were screened to determine a stimulatory drug against the identified target molecule. Finally, the binding affinity and stability of the potential drug candidate(s) against the target were analysed by molecular docking and molecular dynamics simulation. The results revealed that bone morphogenetic protein-4 (BMP-4) was associated with the regulation of the multiple regeneration processes. The computational screening results suggested Retinoic acid and Torularhodin as potential drug candidates for the stimulation of BMP-4. Both drugs demonstrated slightly different but stable interactions with BMP-4, suggesting that the identified drug candidates are likely to serve as potential leads to further enhance tissues regeneration.Communicated by Ramaswamy H. Sarma.

Purpose: Lithium chloride (LiCl) is clinically used for manic disorders. Its role has been shown in improving cell survival by decreasing Bax and p53 expression and increasing Bcl-2 concentration in the cell. This potential of LiCl is responsible for reducing irradiated cell death. In this study, we have explored the role of LiCl as a radioprotectant affecting survival genes. Materials and methods: To find out the cellular response upon LiCl pretreatment to radiation-exposed KG1a cells; viability, clonogenic assay and microarray studies were performed. This was followed by the detection of transcription factor binding motif in coregulated genes. These results were confirmed by reverse transcription-polymerase chain reaction (RT-PCR) and chromatin immunoprecipitation (CHIP). Results: LiCl improved irradiated KG1a cell survival and its clonogenicity at 2 mM concentration (clinically used). Microarray data analysis showed differential expression of cell-protecting genes playing an important role in apoptosis, cell cycle, adhesion and inflammation, etc. The coregulation analysis revealed genes involved in bile acid biosynthesis were also affected by LiCl treatment, these genes are likely to be responsible for radiation-induced gastrointestinal (GI) syndrome through bile production. Conclusions: This is the first study with respect to global genetic expression upon LiCl treatment to radiation-exposed cells. Our results suggest considering repurposing of LiCl as a protective agent for radiation injury.