Background Because of the highly heterogeneous nature of breast cancer, each subtype differs in response to several treatment regimens. This has limited the therapeutic options for metastatic breast cancer disease requiring exploration of diverse therapeutic models to target tumor specific biomarkers. Methods Differentially expressed breast cancer genes identified through extensive data mapping were studied for their interaction with other target proteins involved in breast cancer progression. The molecular mechanisms by which these signature genes are involved in breast cancer metastasis were also studied through pathway analysis. The potential drug targets for these genes were also identified. Results From 50 DEGs, 20 genes were identified based on fold change and p-value and the data curation of these genes helped in shortlisting 8 potential gene signatures that can be used as potential candidates for breast cancer. Their network and pathway analysis clarified the role of these genes in breast cancer and their interaction with other signaling pathways involved in the progression of disease metastasis. The miRNA targets identified through miRDB predictor provided potential miRNA targets for these genes that can be involved in breast cancer progression. Several FDA approved drug targets were identified for the signature genes easing the therapeutic options for breast cancer treatment. Conclusion The study provides a more clarified role of signature genes, their interaction with other genes as well as signaling pathways. The miRNA prediction and the potential drugs identified will aid in assessing the role of these targets in breast cancer.
Background: Colorectal cancer is known to be the most common type of cancer worldwide with high diseaserelated mortality. It is the third most common cancer in men and women and is the second major cause of death globally due to cancer. It is a complicated and fatal disease comprising of a group of molecular heterogeneous disorders. Results: This study identifies the potential biomarkers of CRC through differentially expressed analysis, system biology, and proteomic analysis. Ten publicly available microarray datasets were analyzed and seven potential biomarkers were identified from the list of differentially expressed genes having a p value < 0.05. The expression profiling and the functional enrichment analysis revealed the role of these genes in cell communication, signal transduction, and immune response. The protein-protein interaction showed the functional association of the source genes (CTNNB1, NNMT, PTCH1, CALD1, CXCL14, CXCL8, and TNFAIP3) with the target proteins, such as AXIN, MAPK, IL6, STAT, APC, GSK3B, and SHH. Conclusion: The integrated pathway analysis indicated the role of these genes in important physiological responses, such as cell cycle regulation, WNT, hedgehog, MAPK, and calcium signaling pathways during colorectal cancer. These pathways are involved in cell proliferation, chemotaxis, cellular growth, differentiation, tissue patterning, and cytokine production. The study shows the regulatory role of these genes in colorectal cancer and the pathways that can be effected after the dysregulation of these genes.
The production and up-regulation of inflammatory mediators are contributing factors for the development and maintenance of neuropathic pain. In the present study, the post-treatment of synthetic 1,3,4 oxadiazole derivative (B3) for its neuroprotective potential in chronic constriction injury-induced neuropathic pain was applied. In-silico studies were carried out through Auto Dock, PyRx, and DSV to obtain the possible binding and interactions of the ligands (B3) with COX-2, IL-6, and iNOS. The sciatic nerve of the anesthetized rat was constricted with sutures 3/0. Treatment with 1,3,4-oxadiazole derivative was started a day after surgery and continued until the 14th day. All behavioral studies were executed on day 0, 3rd, 7th, 10th, and 14th. The sciatic nerve and spinal cord were collected for further molecular analysis. The interactions in the form of hydrogen bonding stabilizes the ligand target complex. B3 showed three hydrogen bonds with IL-6. B3, in addition to correcting paw posture/deformation induced by CCI, attenuates hyperalgesia (p < 0.001) and allodynia (p < 0.001). B3 significantly raised the level of GST and GSH in both the sciatic nerve and spinal cord and reduced the LPO and iNOS (p < 0.001). B3 attenuates the pathological changes induced by nerve injury, which was confirmed by H&E staining and IHC examination. B3 down-regulates the over-expression of the inflammatory mediator IL-6 and hence provides neuroprotective effects in CCI-induced pain. The results demonstrate that B3 possess anti-nociceptive and anti-hyperalgesic effects and thus minimizes pain perception and inflammation. The possible underlying mechanism for the neuroprotective effect of B3 probably may be mediated through IL-6.
Aims/introductionDue to the heterogeneous nature of type 2 diabetes mellitus and its complex effects on hemodynamics, there is a need to identify new candidate markers which are involved in the development of type 2 diabetes mellitus (DM) and can serve as potential targets. As the global diabetes prevalence in 2019 was estimated as 9.3% (463 million people), rising to 10.2% (578 million) by 2030 and 10.9% (700 million) by 2045, the need to limit this rapid prevalence is of concern. The study aims to identify the possible biomarkers of type 2 diabetes mellitus with the help of the system biology approach using R programming.Materials and methodsSeveral target proteins that were found to be associated with the source genes were further curated for their role in type 2 diabetes mellitus. The differential expression analysis provided 50 differentially expressed genes by pairwise comparison between the biologically comparable groups out of which eight differentially expressed genes were short-listed. These DEGs were as follows: MCL1, PTX3, CYP3A4, PTGS1, SSTR2, SERPINA3, TDO2, and GALNT7.ResultsThe cluster analysis showed clear differences between the control and treated groups. The functional relationship of the signature genes showed a protein–protein interaction network with the target protein. Moreover, several transcriptional factors such as DBX2, HOXB7, POU3F4, MSX2, EBF1, and E4F1 showed association with these identified differentially expressed genes.ConclusionsThe study highlighted the important markers for diabetes mellitus that have shown interaction with other proteins having a role in the progression of diabetes mellitus that can serve as new targets in the management of DM.
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