Epithelial mesenchymal transition induced nuclear localization of the extracellular matrix protein Fibronectin.

Fibronectin (FN), an extracellular matrix (ECM) glycoprotein, is a well-known marker for Epithelial Mesenchymal Transition (EMT). In the ECM, FN has been shown to form long fibrils and play critical roles in regulating cellular attachment and migration during EMT associated with physiological processes such as embryonic development, wound healing as well as pathological processes such as tissue fibrosis and cancer. Subsequently, the cytokine, Transforming Growth Factor ß (TGFß), an inducer of EMT, was found to induce FN expression in a c-Jun N-terminal kinase (JNK) dependent manner. Moreover, extracellular FN, by itself, was also shown to induce EMT in breast epithelial cells in serum-free condition. Collectively, all the literature published so far has shown and established the role of extracellular FN during EMT. In this report, we have shown that EMT induced entry of FN into the nucleus of mouse breast epithelial cells. To our knowledge, this is the first report showing nuclear localization of the extracellular matrix protein Fibronectin during EMT and thereby suggests a possible nuclear function for the ECM protein.

Donor-Derived Cell-Free DNA as a Non-Invasive Biomarker for Graft Rejection in Kidney Transplant Recipients: A Prospective Study among the Indian Population.

Monitoring graft health and detecting graft rejection is crucial for the success of post-transplantation outcomes. In Western countries, the use of donor-derived cell-free DNA (dd-cfDNA) has gained widespread recognition as a diagnostic tool for kidney transplant recipients. However, the role of dd-cfDNA among the Indian population remains unexplored. The recipients were categorized into two groups: the post-transplant recipient (PTR) group (n = 16) and the random recipient (RR) group (n = 87). Blood samples were collected daily from the PTR group over a 7-day period, whereas the RR group's samples were obtained at varying intervals. In this study, we used a targeted approach to identify dd-cfDNA, which eliminated the need for genotyping, and is based on the minor allele frequency of SNP assays. In the PTR group, elevated dd-cfDNA% levels were observed immediately after transplantation, but returned to normal levels within five days. Within the RR group, heightened serum creatinine levels were directly proportional to increased dd-cfDNA%. Sixteen recipients were advised to undergo biopsy due to elevated serum creatinine and other pathological markers. Among these sixteen recipients, six experienced antibody-mediated rejection (ABMR), two exhibited graft dysfunctions, two had active graft injury, and six (37.5%) recipients showed no rejection (NR). In cases of biopsy-proven ABMR and NR, recipients displayed a mean ± SD dd-cfDNA% of 2.80 ± 1.77 and 0.30 ± 0.35, respectively. This study found that the selected SNP assays exhibit a high proficiency in identifying donor DNA. This study also supports the use of dd-cfDNA as a routine diagnostic test for kidney transplant recipients, along with biopsies and serum creatinine, to attain better graft monitoring.

Epithelial-mesenchymal transition and its transcription factors.

Epithelial-mesenchymal transition or EMT is an extremely dynamic process involved in conversion of epithelial cells into mesenchymal cells, stimulated by an ensemble of signaling pathways, leading to change in cellular morphology, suppression of epithelial characters and acquisition of properties such as enhanced cell motility and invasiveness, reduced cell death by apoptosis, resistance to chemotherapeutic drugs etc. Significantly, EMT has been found to play a crucial role during embryonic development, tissue fibrosis and would healing, as well as during cancer metastasis. Over the years, work from various laboratories have identified a rather large number of transcription factors (TFs) including the master regulators of EMT, with the ability to regulate the EMT process directly. In this review, we put together these EMT TFs and discussed their role in the process. We have also tried to focus on their mechanism of action, their interdependency, and the large regulatory network they form. Subsequently, it has become clear that the composition and structure of the transcriptional regulatory network behind EMT probably varies based upon various physiological and pathological contexts, or even in a cell/tissue type-dependent manner.

Omicron variant: Current insights and future directions.

The global COVID-19 outbreak has returned with the identification of the SARS-CoV-2 Omicron variant (B.1.1.529) after appearing to be persistently spreading for the more than past two years. In comparison to prior SARS-CoV-2 variants, this new variant revealed a significant amount of mutation. This novel variety may have a greater rate of transmissibility which might impede the effectiveness of current diagnostic equipment as well as vaccination efficacy and also impede immunotherapies (Antibody / monoclonal antibody based). WHO designated B.1.1.529 as a variant of concern on November 26, 2021, identified as Omicron. The Omicron variant transmission method and severity, on the other hand, are well defined. The global spread of Omicron, which has now seized many nations, has resulted in numerous speculations regarding its origin and degree of infectivity. The following sections will go over its potential for transmission, omicron structure, and impact on COVID-19 vaccines, how it is different from delta variant and diagnostics.

Cytochrome C as a potential clinical marker for diagnosis and treatment of glioma.

Gliomas are the most prevalent kind of malignant and severe brain cancer. Apoptosis regulating mechanisms are disturbed in malignant gliomas, as they are in added forms of malignancy. Understanding apoptosis and other associated processes are thought to be critical for understanding the origins of malignant tumors and designing anti-cancerous drugs for the treatment. The purpose of this study was to evaluate the variation in the expression level of several apoptotic proteins that are responsible for apoptosis in low to high-grade glioma. This suggests a significant change in the expression of five apoptotic proteins: Clusterin, HSP27, Catalase, Cytochrome C, and SMAC. Cytochrome C, one of the five substantially altered proteins, is a crucial component of the apoptotic cascade. The complex enzyme Cytochrome C is involved in metabolic pathways such as respiration and cell death. The results demonstrated that Cytochrome C expression levels are lower in glioma tissues than in normal tissues. What's more intriguing is that the expression level decreases with an increase in glioma grades. As a result, the discovery shows that Cytochrome C may be a target for glioma prognostic biomarkers.