Background: Endothelial dysfunction (ED) has emerged as a critical process in cardiorenal syndrome (CRS). The concept that ED is closely linked with cardiac and r

/pdf/the-central-role-of-endothelial-dysfunction-in-cardiorenal-3gn9g1yqqo.pdf

The Central Role of Endothelial Dysfunction in Cardiorenal Syndrome

https://espace.library.uq.edu.au/view/UQ:8de62da/UQ8de62da_OA.pdf

Oxidative stress: Normal pregnancy versus preeclampsia

Genetics ultimately defines an individual, yet the phenotype of an adult is extensively determined by the sequence of lifelong exposures, termed the exposome. The redox theory of aging recognizes that animals evolved within an oxygen-rich environment, which created a critical redox interface between an organism and its environment. Advances in redox biology show that redox elements are present throughout metabolic and structural systems and operate as functional networks to support the genome in adaptation to environmental resources and challenges during lifespan. These principles emphasize that physical and functional phenotypes of an adult are determined by gene-environment interactions from early life onward. The principles highlight the critical nature of cumulative exposure memories in defining changes in resilience progressively during life. Both plasma glutathione and cysteine systems become oxidized with aging, and the recent finding that cystine to glutathione ratio in human plasma predicts death in coronary artery disease (CAD) patients suggests this could provide a way to measure resilience of redox networks in aging and disease. The emerging concepts of cumulative gene-environment interactions warrant focused efforts to elucidate central mechanisms by which exposure memory governs health and etiology, onset and progression of disease.

Redox theory of aging: implications for health and disease.

In this paper, a pilot production process for mesenchymal stem/stromal freeze-dried secretome was performed in a validated good manufacturing practice (GMP)-compliant cell factory. Secretome was purified from culture supernatants by ultrafiltration, added to cryoprotectant, lyophilized and characterized. We obtained a freeze-dried, “ready-off-the-shelf” and free soluble powder containing extracellular vesicles and proteins. In the freeze-dried product, a not-aggregated population of extracellular vesicles was detected by nanoparticle tracking analysis; Fourier transform infrared spectra showed the simultaneous presence of protein and lipids, while differential scanning calorimetry demonstrated that lyophilization process successfully occurred. A proteomic characterization allowed the identification of proteins involved in immune response, response to stress, cytoskeleton and metabolism. Moreover, the product was not cytotoxic up to concentrations of 25 mg/mL (on human fibroblasts, chondrocytes and nucleus pulposus cells by MTT assay) and was blood compatible up to 150 mg/mL. Finally, at concentrations between 5 and 50 mg/mL, freeze-dried secretome showed to in vitro counteract the oxidative stress damage induced by H2O2 on nucleus pulposus cells by MTT assay.

Pilot Production of Mesenchymal Stem/Stromal Freeze-Dried Secretome for Cell-Free Regenerative Nanomedicine: A Validated GMP-Compliant Process

Background A common phenotype associated with heart failure is the development of cardiac hypertrophy. Cardiac hypertrophy occurs in response to stress, such as hypertension, coronary vascular disease, or myocardial infarction. The most critical pathophysiological conditions involved may include dilated hypertrophy, fibrosis and contractile malfunction. The intricate pathophysiological mechanisms of cardiac hypertrophy have been the core of several scientific studies, which may help in opening a new avenue in preventive and curative procedures. Objectives To our knowledge from the literature, the development of cardiac remodeling and hypertrophy is multifactorial. Thus, in this review, we will focus and summarize the potential role of oxidative stress in cardiac hypertrophy development. Conclusion Oxidative stress is considered a major stimulant for the signal transduction in cardiac cells pathological conditions, including inflammatory cytokines, and MAP kinase. The understanding of the pathophysiological mechanisms which are involved in cardiac hypertrophy and remodeling process is crucial for the development of new therapeutic plans, especially that the mortality rates related to cardiac remodeling/dysfunction remain high.

/pdf/oxidative-stress-and-cardiac-remodeling-an-updated-edge-2wwji3j041.pdf

Oxidative Stress and Cardiac Remodeling: An Updated Edge.

Free radicals or reactive oxygen species (ROS) are generated by oxygen metabolism which is balanced by the rate of oxidant formation and the rate of oxidant elimination. Oxidative stress is a result of imbalance between the generation of reactive oxygen species (ROS) and the antioxidant defence systems. Hypertension is one of the major risk factors for cardiovascular diseases and is considered as a leading cause of mortality and morbidity. These diseases affect more than 600 million people and it has been estimated that 29% of the world population will be suffering from hypertension by 2025. It has been indicated by experimental evidence that reactive oxygen species (ROS) play an important role in the pathophysiology of hypertension. The vasculature is a rich source of NADPH oxidase which produces most of the reactive oxygen species and plays an important role in renal dysfunction and vascular damage. Recent studies indicate that increased oxidative stress is the important mediator of endothelial injury in the pathology of hypertension associated to increased production of pro oxidants such as superoxideanion hydrogen peroxide, reduced nitric oxide synthesis and decreased bioavailability of antioxidants. Oxidative stress is found to be associated with endothelial dysfunction, inflammation, hypertrophy, apoptosis, cell migration, fibrosis, and angiogenesis in relation to vascular remodelling of hypertension. Results in humans are still less conclusive inspite of data available that involve oxidative stress as a causative factor of essential hypertension. The aim of this review is to present a novel focus on the role of oxidative stress in the pathophysiology of hypertension and recent biomarkers which are found to be associated with reactive oxygen species and the role of antioxidants as therapy of hypertension.

Oxidative stress and antioxidants in hypertension-a current review.

MicroRNAs (miRNAs) are a group of small RNAs, with around 19 to 25 nucleotides, which results from cleavage of larger non- coding RNAs. They act as regulators of gene expression post- transcriptionally both in plants and in animals. The first miRNA was discovered in 1993 by Victor Ambros and colleagues Rosalind Lee and Rhonda Feinbaum. Subsequently, many more short regulatory RNAs were identified in almost all multicellular organisms, including flowering plants, worms, flies, fish, mammals and in single cellular algae and DNA viruses. More than 500 human miRNAs have been experimentally identified till date. It has been studied by computational predictions of miRNA that up to 30% of human protein coding genes may be regulated by miRNAs. This makes miRNAs one of the most abundant groups of regulatory genes in human body. MicroRNAs are now perceived as a key layer of post- transcriptional control within the networks of gene regulation.

Nakshi Sinha

Papers

Oxidative stress and antioxidants in hypertension-a current review.

Biological and Clinical Implications of Micro-RNA in the Pathogenesis of Cancer and Human Diseases