The intervention of epithelial-mesenchymal transition in homeostasis of human retinal pigment epithelial cells: a review.

The health and activity of photoreceptors and Bruch's membrane are promoted by the retinal pigment epithelium (RPE), which is essential for normal vision. Age-related macular degeneration (AMD), diabetic retinopathy (DR), and proliferative vitreoretinopathy (PVR) are examples of retinopathies that result in vision loss. Epithelial-mesenchymal transition (EMT) is a process in which epithelial cells transform into mesenchymal cells as a result of a faulty microenvironment, and it is associated with the oculopathies stated above. Cell differentiation, autophagy, growth factors (GFs), the blood-retinal barrier (BRB), and other complicated signaling pathways all contribute to proper morphology, and their disruption by harmful compounds has an impact on RPE function. The inducer and suppressor of EMT in RPE, on the other hand, are unknown. The current article reviews the experimental research investigations, suggested that certain modulators like glucosamine (Glc-N) and bradykinin (BK) suppress the TGFß signaling pathway and that other variables like oxidative stress triggered EMT, which is not found in normal RPE homeostasis. Finding molecular targets and treatments to prevent and restore RPE function, as well as understanding how EMT regulators affect RPE degeneration, are therefore crucial.

Network pharmacology-based evaluation of natural compounds with paclitaxel for the treatment of metastatic breast cancer.

Metastatic breast cancer is a prevalent life-threatening disease. Paclitaxel (PTX) is widely used in metastatic breast cancer therapy, but the side effects limit its chemotherapeutic application. Multidrug strategies have recently been used to maximize potency and decrease the toxicity of a particular drug by reducing its dosage. Therefore, we have evaluated the combined anti-cancerous effect of PTX with tested natural compounds (andrographolide (AND), silibinin (SIL), mimosine (MIM) and trans-anethole (TA)) using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, trypan blue dye exclusion assay, proliferating cell nuclear antigen (PCNA) staining, network pharmacology, molecular docking, molecular dynamics (MD) and in vivo chick chorioallantoic membrane (CAM) angiogenesis assay. We observed a reduction in the IC50 value of PTX with tested natural compounds. Further, the network pharmacology-based analysis of compound-disease-target (C-D-T) network showed that PTX, AND, SIL, MIM and TA targeted 55, 61, 56, 31 and 18 proteins of metastatic breast cancer, respectively. Molecular docking results indicated that AND and SIL inhibited the C-D-T network's core target kinase insert domain receptor (KDR) protein more effectively than others. While MD showed that the binding of AND with KDR was stronger and more stable than others. In trypan blue dye exclusion assay and PCNA staining, AND and SIL along with PTX were found to be more effective than PTX alone. CAM assay results suggested that AND, SIL and TA increase the anti-angiogenic potential of PTX. Thus, natural compounds can be used to improve the anti-cancer potential of PTX.