ABSTRACT
BACKGROUND: Insulin producing cells generated by liver cell transdifferentiation, could serve as an attractive source for regenerative medicine. The present study assesses the relationship between DNA methylation pTFs induced liver to pancreas transdifferentiation. RESULTS: The transdifferentiation process is associated with DNA demethylation, mainly at gene regulatory sites, and with increased expression of these genes. Active inhibition of DNA methylation promotes the pancreatic transcription factor-induced transdifferentiation process, supporting a causal role for DNA demethylation in this process. CONCLUSIONS: Transdifferentiation is associated with global DNA hypomethylation, and with increased expression of specific demethylated genes. A combination of epigenetic modulators may be used to increase chromatin accessibility of the pancreatic transcription factors, thus promoting the efficiency of the developmental process.
Subject(s)
DNA Demethylation , Insulins , Cell Transdifferentiation/genetics , Chromatin , DNA , Insulins/genetics , Liver , Pancreas , Transcription Factors/geneticsABSTRACT
Angiogenesis is a multi-stage process of new blood vessel development from pre-existing vessels toward an angiogenic stimulus. The process is essential for tissue maintenance and homeostasis during embryonic development and adult life as well as tumor growth. Under normal conditions, angiogenesis is involved in physiological processes, such as wound healing, cyclic regeneration of the endometrium, placental development and repairing certain cardiac damage, in pathological conditions, it is frequently associated with cancer development and metastasis. The control mechanisms of angiogenesis in carcinogenesis are tightly regulated at the genetic and epigenetic level. While genetic alterations are the critical part of gene silencing in cancer cells, epigenetic dysregulation can lead to repression of tumor suppressor genes or oncogene activation, becoming an important event in early development and the late stages of tumor development, as well. The global alteration of the epigenetic spectrum, which includes DNA methylation, histone modification, chromatin remodeling, microRNAs, and other chromatin components, is considered one of the hallmarks of cancer, and the efforts are concentrated on the discovery of molecular epigenetic markers that identify cancerous precursor lesions or early stage cancer. This review aims to highlight recent findings on the genetic and epigenetic changes that can occur in physiological and pathological angiogenesis and analyze current knowledge on how deregulation of epigenetic modifiers contributes to tumorigenesis and tumor maintenance. Also, we will evaluate the clinical relevance of epigenetic markers of angiogenesis and the potential use of "epi-drugs" in modulating the responsiveness of cancer cells to anticancer therapy through chemotherapy, radiotherapy, immunotherapy and hormone therapy as anti-angiogenic strategies in cancer.
ABSTRACT
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the caused disease - coronavirus disease 2019 (COVID-19), has affected so far >6,000,000 people worldwide, with variable grades of severity, and has already inflicted >350,000 deaths. SARS-CoV-2 infection seems severely affected by background diseases such as diabetes mellitus and its related complications, that seem to be favoring the most severe manifestations of SARS-CoV-2 and, therefore, require special attention in clinical care units. The present literature review focus on addressing several hypotheses explaining why diabetic patients could develop multi-organ failure in severe acute respiratory syndrome coronavirus (SARS-CoV) infections. Undoubtedly, as diabetes related complications are present it is expected to emphasize the severity of the COVID-19. Dermatological complications can occur and worsen in diabetic patients, and diseases such as acanthosis nigricans and psoriasis are prone to more severe manifestations of COVID-19. Approaches to treat SARS-CoV-2 infected patients, based on different solutions i.e. plasma therapy, use of antiviral compounds, development of vaccines or new therapeutic agents are ongoing.
