Purpose: At the molecular level, disc degeneration (DD) has been associated with dissociation of matrix assembly, leading to the loss of structural integrity. As a result of matrix dissociation, tissue ECM proteins are expected to leak into the newly developed blood vessels that circulate in the peripheral blood, indicating diseased states. Experimental design: To identify the IVD tissue-ECM proteins leaked into diseased plasma, global proteomic analysis was performed on 10 healthy volunteers (HV) and 10 diseased subjects (DS) after depletion of highly abundant proteins such as Albumin and IgG. Results: 28 proteins were identified as matrix-associated proteins identical to the proteins found in intervertebral disc tissues. Of these, 26 were from DS and 21 from HV. Among these candidates, aggrecan and fibulin 1 were found to be up and downregulated significantly in the DS group. Interestingly, diseased plasma had a specific expression of COL2A1, native to the nucleus pulposus. Conclusions and clinical relevance: The upregulated and unique presence of aggrecan and collagen type 2A1 respectively in diseased plasma remains indicative of intervertebral disc disease progression. This identification could aid in understanding the altered protein signature that remains indicative of tissue damage and the circulation of damaged tissue products.

Background and Purpose: The aromatase enzyme plays a fundamental role in addressing the development of estrogen receptors and giving attention to the therapy of reproductive disorders and cancer diseases. In clinical use, the objectionable effects found in these target inhibitors are indispensable in finding novel aromatase inhibitors with more selective, less toxic, and more effective drug potency. Experimental Approach: The research framework of this study is to identify a potent inhibitor for the aromatase target by profiling molecular descriptors of the ligand and finding a functional pocket of the target by docking and MD simulations. For assessing cellular metabolic activities as an indicator of cell viability and cytotoxicity, in-vitro studies were performed by using colorimetric MTT assay. Cell morphology was assessed by phase-contrast light microscope. Cell cycle distribution and apoptosis were determined by flowcytometry and Annexin V-FITC/PI staining assay. Key Results: This study reported herein the most promising compound CHEMBL598797 (Ziprasidone) showed excellent activity potential to inhibit aromatase in search of finding the novel compound based on better drug design methods and experimental studies and could be effective as the high potential drug candidate against aromatase enzyme. Conclusion and Implications: We concluded that the compound ziprasidone effectively blocks the cell cycle at the G1-S phase and induces cancer cell death. Further in-vivo studies can be evaluated for developing this compound as an anticancer agent. Overall, our outcomes based on the in-silico and the high-quality experimental results may pave the way for identifying effective drug candidates for better therapeutic interest for breast cancer.