Description

The pathological hallmark of Proliferative Diabetic Retinopathy (PDR) is ischemia-induced pathological growth of new blood vessels and expansion of Extracellular Matrix (ECM) in association with the outgrowth of fibro vascular epiretinal membranes at the vitreoretinal interface, which frequently results in catastrophic loss of vision due to vitreous haemorrhage and/or traction retinal detachment. Although the aetiology of fibrotic illnesses is highly different, and their pathophysiology is variable and depending on the causative agent or starting event, the presence of large numbers of myofibroblast and aberrant ECM build-up in the afflicted tissue is a common trait (s). Myofibroblast, the primary cellular mediators of fibrosis, are contractile cells that express -smooth muscle actin (-SMA), and their presence is associated with increasing fibrosis. They can manufacture many ECM components, including collagen, leading in fibrosis. 1 Inflammatory and fibrotic alterations in the epiretinal membranes of PDR patients are characterised by the presence of inflammatory cells and -SMA-expressing myofibroblast in the stromal compartment. The origin(s) of myofibroblast responsible for the excessive and unregulated synthesis of ECM proteins in PDR epiretinal membranes remain unknown. Endothelial cells may undergo Endothelial-to-Mesenchymal Transition (EndoMT) or Endothelial-to-Myofibroblast Transition (EndoMT) under normal and pathological conditions, according to growing data. 4 Endothelial cells lose their adherence and apical-basal polarity during EndoMT, resulting in highly invasive migratory spindle-shaped elongated mesenchymal cells. More crucially, biochemical alterations, such as reduced expression of endothelium markers, follow these unique changes in cell polarity and shape. CD31, VE-cadherin, and endothelial Nitric Oxide Synthase (eNOS), as well as the acquisition of mesenchymal markers such as -SMA, Fibroblast-Specific Protein-1 (FSP-1, also known as S100A4), calponin, and smooth muscle protein 22 (or transgenic). 4 Transitional cells may have both endothelial and mesenchymal characteristics. We recently investigated the possibility that EndoMT contributes to the myofibroblast population seen in the epiretinal membranes of PDR patients. To learn more about probable EndoMT, we double-labelled CD31/FSP-1 and CD31/-SMA. For the first time, we found that endothelial cells in epiretinal fibrovascular membranes from PDR patients contribute to the formation of fibroblasts/myofibroblasts via the EndoMT process. We discovered that certain CD31-expressing endothelial cells also express the fibroblast marker FSP-1 and the myofibroblast marker -SMA. The presence of CD31+/FSP-1+ and CD31+/-SMA+ cells shows that EndoMT is in an intermediate stage. Our findings imply that EndoMT is involved in the formation of fibroblasts and myofibroblasts, which are responsible for fibrosis and the advancement of PDR. EndoMT may potentially contribute to the loss of endothelial cells in PDR epiretinal membranes and the spontaneous regression of new blood vessels in individuals with end-stage PDR, according to these studies. Finally, we showed that transforming growth factor-1 and the proinflammatory cytokines interleukin-1 and tumour necrosis factor-induce phenotypic alterations in Human Retinal Microvascular Endothelial Cells (HRMEC). Endothelial cells in stimulated cell cultures altered shape, decreased endothelial cell markers, and increased endothelial cell markers. Markers of mesenchymal/myofibroblast differentiation. These data support the theory that EndoMT might contribute to the fibrotic process that occurs during PDR. A better knowledge of the molecular processes involved in the EndoMT process, as well as pharmacological blocking of these pathways, might constitute a potential therapeutic option for slowing the advancement of fibrosis associated with PDR. Lung cancer continues to be a disease marked by early metastases and low 5-year survival. Lung malignancies are nearly entirely generated from epithelial tissues, and the majority of tumour cells retain epithelial properties even as the tumour grows. However, a small proportion of cells are expected to go through an epithelial to mesenchymal transition, in which the malignant cells develop a fibroblast-like shape and lose intracellular adhesions and move about. This is an important step in cancer invasion and metastasis. These mesenchymal cells may eventually convert to an epithelial phenotype, allowing clinically meaningful metastasis development. Ongoing research is needed to identify how the epithelial to mesenchymal transition process may be used in lung cancer patients for screening, diagnostic investigations, and treatment choices. Lung cancer is still the leading cause of cancer-related mortality in both men and women in America, killing more people than melanoma, colorectal, breast, and prostate cancer combined. 1 Overall 5-year survival for individuals with Non-small Cell Lung Cancer (NSCLC) remains poor at 15%, owing mostly to the development of distant metastatic disease. Despite the hope that curative surgical excision of early stage NSCLC will result in disease-free people, 40% to 60% of these patients will develop metastases and die from lung cancer. The best current chemotherapeutic drugs' efficacy in controlling metastasis has hit a plateau, and future progress of cytotoxic treatment is doubtful. Following the advent of antibodies and small molecule inhibitors of epithelial growth factor receptor and vascular endothelial growth factor, targeted agents have lately sparked attention. However, novel drugs administered against these receptors produce survival advantages only in a subset of patients, and the use of targeted therapies in the general population of lung cancer patients delivers only moderate improvements.