SIRT-associated attenuation of cellular senescence in vascular wall.

This review focuses on the vital function that SIRT1 and other sirtuins play in promoting cellular senescence in vascular smooth muscle cells, which is a key element in the pathogenesis of vascular aging and associated cardiovascular diseases. Vascular aging is a gradual process caused by the accumulation of senescent cells, which results in increased vascular remodeling, stiffness, and diminished angiogenic ability. Such physiological alterations are characterized by a complex interplay of environmental and genetic variables, including oxidative stress and telomere attrition, which affect gene expression patterns and trigger cell growth arrest. SIRT1 has been highlighted for its potential to reduce cellular senescence through modulation of multiple signaling cascades, particularly the endothelial nitric oxide (eNOS)/NO signaling pathway. It also modulates cell cycle through p53 inactivation and suppresses NF-κB mediated expression of adhesive molecules at the vascular level. The study also examines the therapeutic potential of sirtuin modulation in vascular health, identifying SIRT1 and its sirtuin counterparts as potential targets for reducing vascular aging. This study sheds light on the molecular basis of vascular aging and the beneficial effects of sirtuins, paving the way for the development of tailored therapies aimed at enhancing vascular health and prolonging life.

Comprehensive Assessment of Graphene Oxide Nanoparticles: Effects on Liver Enzymes and Cardiovascular System in Animal Models and Skeletal Muscle Cells.

The growing interest in graphene oxide (GO) for different biomedical applications requires thoroughly examining its safety. Therefore, there is an urgent need for reliable data on how GO nanoparticles affect healthy cells and organs. In the current work, we adopted a comprehensive approach to assess the influence of GO and its polyethylene glycol-modified form (GO-PEG) under near-infrared (NIR) exposure on several biological aspects. We evaluated the contractility of isolated frog hearts, the activity of two rat liver enzymes-mitochondrial ATPase and diamine oxidase (DAO), and the production of reactive oxygen species (ROS) in C2C12 skeletal muscle cells following direct exposure to GO nanoparticles. The aim was to study the influence of GO nanoparticles at multiple levels-organ; cellular; and subcellular-to provide a broader understanding of their effects. Our data demonstrated that GO and GO-PEG negatively affect heart contractility in frogs, inducing stronger arrhythmic contractions. They increased ROS production in C2C12 myoblasts, whose effects diminished after NIR irradiation. Both nanoparticles in the rat liver significantly stimulated DAO activity, with amplification of this effect after NIR irradiation. GO did not uncouple intact rat liver mitochondria but caused a concentration-dependent decline in ATPase activity in freeze/thaw mitochondria. This multifaceted investigation provides crucial insights into GOs potential for diverse implications in biological systems.

Anticarcinogenic Potency of EF24: An Overview of Its Pharmacokinetics, Efficacy, Mechanism of Action, and Nanoformulation for Drug Delivery.

EF24, a synthetic monocarbonyl analog of curcumin, shows significant potential as an anticancer agent with both chemopreventive and chemotherapeutic properties. It exhibits rapid absorption, extensive tissue distribution, and efficient metabolism, ensuring optimal bioavailability and sustained exposure of the target tissues. The ability of EF24 to penetrate biological barriers and accumulate at tumor sites makes it advantageous for effective cancer treatment. Studies have demonstrated EF24's remarkable efficacy against various cancers, including breast, lung, prostate, colon, and pancreatic cancer. The unique mechanism of action of EF24 involves modulation of the nuclear factor-kappa B (NF-κB) and nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathways, disrupting cancer-promoting inflammation and oxidative stress. EF24 inhibits tumor growth by inducing cell cycle arrest and apoptosis, mainly through inhibiting the NF-κB pathway and by regulating key genes by modulating microRNA (miRNA) expression or the proteasomal pathway. In summary, EF24 is a promising anticancer compound with a unique mechanism of action that makes it effective against various cancers. Its ability to enhance the effects of conventional therapies, coupled with improvements in drug delivery systems, could make it a valuable asset in cancer treatment. However, addressing its solubility and stability challenges will be crucial for its successful clinical application.

Oxidative Stress, Reductive Stress and Antioxidants in Vascular Pathogenesis and Aging.

This review is focused on the mechanisms that regulate health, disease and aging redox status, the signal pathways that counteract oxidative and reductive stress, the role of food components and additives with antioxidant properties (curcumin, polyphenols, vitamins, carotenoids, flavonoids, etc.), and the role of the hormones irisin and melatonin in the redox homeostasis of animal and human cells. The correlations between the deviation from optimal redox conditions and inflammation, allergic, aging and autoimmune responses are discussed. Special attention is given to the vascular system, kidney, liver and brain oxidative stress processes. The role of hydrogen peroxide as an intracellular and paracrine signal molecule is also reviewed. The cyanotoxins ß-N-methylamino-l-alanine (BMAA), cylindrospermopsin, microcystins and nodularins are introduced as potentially dangerous food and environment pro-oxidants.

ß-N-Methylamino-L-Alanine (BMAA) Modulates the Sympathetic Regulation and Homeostasis of Polyamines.

The neurotoxin ß-N-methylamino-L-alanine (BMAA) is a non-proteinogenic amino acid produced by cyanobacteria. Non-neuronal toxicity of BMAA is poorly studied with a reported increase in reactive oxygen species and a decrease in the antioxidant capacity of liver, kidney, and colorectal adenocarcinoma cells. The aim of this research is to study the toxicity of BMAA (0.1-1 mM) on mitochondria and submitochondrial particles with ATPase activity, on the semicarbazide-sensitive amino oxidases (SSAOs) activity of rat liver, and on an in vitro model containing functionally active excitable tissues-regularly contracting heart muscle preparation with a preserved autonomic innervation. For the first time the BMAA-dependent inhibition of SSAO activity, the elimination of the positive inotropic effect of adrenergic innervation, and the direct and reversible inhibition of adrenaline signaling in ventricular myocytes with 1 mM BMAA were observed. Additionally, it is confirmed that 1 mM BMAA can activate mitochondrial ATPase indirectly. It is concluded that a higher dose of BMAA may influence multiple physiological and pathological processes as it slows down the degradation of biogenic amines, downregulates the sympathetic neuromediation, and embarrasses the cell signaling of adrenergic receptors.

Review of Cyanotoxicity Studies Based on Cell Cultures.

Cyanotoxins (CTs) are a large and diverse group of toxins produced by the peculiar photosynthetic prokaryotes of the domain Cyanoprokaryota. Toxin-producing aquatic cyanoprokaryotes can develop in mass, causing "water blooms" or "cyanoblooms," which may lead to environmental disaster-water poisoning, extinction of aquatic life, and even to human death. CT studies on single cells and cells in culture are an important stage of toxicological studies with increasing impact for their further use for scientific and clinical purposes, and for policies of environmental protection. The higher cost of animal use and continuous resistance to the use of animals for scientific and toxicological studies lead to a progressive increase of cell lines use. This review aims to present (1) the important results of the effects of CT on human and animal cell lines, (2) the methods and concentrations used to obtain these results, (3) the studied cell lines and their tissues of origin, and (4) the intracellular targets of CT. CTs reviewed are presented in alphabetical order as follows: aeruginosins, anatoxins, BMAA (ß-N-methylamino-L-alanine), cylindrospermopsins, depsipeptides, lipopolysaccharides, lyngbyatoxins, microcystins, nodularins, cyanobacterial retinoids, and saxitoxins. The presence of all these data in a review allows in one look to advance the research on CT using cell cultures by facilitating the selection of the most appropriate methods, conditions, and cell lines for future toxicological, pharmacological, and physiological studies.

New Data on Cylindrospermopsin Toxicity.

Cylindrospermopsin (CYN) is a widely spread cyanotoxin that can occur in fresh water and food. This research aims to investigate CYN toxicity by studying the effects of drinking 0.25 nM of CYN-contaminated water from a natural source, and of the direct application of moderate concentrations of CYN on different animal targets. The chosen structures and activities are rat mitochondria inner membrane permeability, mitochondrial ATP synthase (ATPase) and rat liver diamine oxidase (DAO) activities (EC 1.4.3.22.), the force of the contraction of an excised frog heart preparation with functional innervation, and the viability of a human intestinal epithelial cell line (HIEC-6). The oral exposure to CYN decreased the reverse (hydrolase) activity of rat liver ATPase whereas its short-term, in vitro application was without significant effect on this organelle, DAO activity, heart contractions, and their neuronal regulation. The application of CYN reduced HIEC-6 cells' viability dose dependently. It was concluded that CYN is moderately toxic for the human intestinal epithelial cells, where the regeneration of the epithelial layer can be suppressed by CYN. This result suggests that CYN may provoke pathological changes in the human gastrointestinal tract.