Stroke is currently one of the most common causes of death and disability in the world, and its pathophysiology is a complex process, involving the oxidative stress and inflammatory reaction. Unfortunately, no biochemical factors useful in the diagnostics and treatment of stroke have been clearly established to date. Therefore, researchers are increasingly interested in the inflammatory response triggered by cerebral ischemia and its role in the development of cerebral infarction. This article gives an overview of the available literature data concerning the role of pro-inflammatory cytokines in acute stroke. Detailed analysis of their role in cerebral circulation disturbances can also suggest certain immune response regulatory mechanisms aimed to reduce damage to the nervous tissue in the course of stroke.
Introduction: Since 1956 there have been numerous scientific articles about free radical theory of aging which both confirm and deny the theory. Due to oxygen metabolism, there are relatively high concentrations of molecular oxygen in human cells, especially in mitochondria. Under normal physiological conditions, a small fraction of oxygen is constantly converted to ROS, such as superoxide radical (O2−•,), H2O2, and related metabolites. Aim of the study: The aim of this work was to show the relation between the activity of main antioxidative enzymes and the age of the examined patients. Materials and methods: The analysis of antioxidant defense was performed on the blood samples from 184 “aged“ individuals aged 65–90+ years, and compared to the blood samples of 37 individuals just about at the beginning of aging, aged 55–59 years. Results: The statistically significant decreases of Zn,Cu-superoxide dismutase (SOD-1), catalase (CAT), and glutathione peroxidase (GSH-Px) activities were observed in elderly people in comparison with the control group. Moreover, an inverse correlation between the activities of SOD-1, CAT, and GSH-Px and the age of the examined persons was found. No age-related changes in glutathione reductase activities and malondialdehyde concentrations were observed. Conclusion: Lower activities of fundamental antioxidant enzymes in the erythrocytes of elderly people, which indicate the impairment of antioxidant defense in the aging organism and the intensity of peroxidative lipid structures, were observed.
Dyslipidemia is listed among important cardiovascular disease risk factors. Treating lipid disorders is difficult, and achieving desirable levels of LDL-cholesterol (LDL-C) is essential in both the secondary and primary prevention of cardiovascular disease. For many years, statins became the basis of lipid-lowering therapy. Nevertheless, these drugs are often insufficient due to their side effects and restrictive criteria for achieving the recommended LDL-C values. Even the addition of other drugs, i.e., ezetimibe, does not help one achieve the target LDL-C. The discovery of proprotein convertase subtilisin/kexin type 9 (PCSK9) discovery has triggered intensive research on a new class of protein-based drugs. The protein PCSK9 is located mainly in hepatocytes and is involved in the metabolism of LDL-C. In the beginning, antibodies against the PCSK9 protein, such as evolocumab, were invented. The next step was inclisiran. Inclisiran is a small interfering RNA (siRNA) that inhibits the expression of PCSK9 by binding specifically to the mRNA precursor of PCSK9 protein and causing its degradation. It has been noticed in recent years that siRNA is a powerful tool for biomedical research and drug discovery. The purpose of this work is to summarize the molecular mechanisms, pharmacokinetics, pharmacodynamics of inclisiran and to review the latest research.
During a stroke, a series of biochemical and metabolic changes occur which eventually lead to the death of cells by necrosis or apoptosis. This is a multi-stage process involving oxidative stress and an inflammatory response from the first signs of occlusion of a blood vessel until the late stages of regeneration and healing of ischemic tissues. The purpose of the research was to assess the concentration of pro-inflammatory cytokines IL-6 and TNF-α in the blood serum of patients with ischemic stroke (AIS) and to investigate their role as new markers in predicting functional prognosis after thrombolytic therapy. The researches have shown that the concentrations of the measured biomarkers were higher compared to the control group. Serum levels of IL-6 and THF-α before the initiation of intravenous thrombolysis were lower in the subgroup of patients with a favourable functional result (mRS: 0–2 pts) compared to the group of patients with an unfavourable functional result (mRS: 3–6 pts). A positive correlation was found between the concentration of IL-6 and TNF-α in patients with AIS during <4.5 h and on one day after the onset of stroke, which means that the concentration of IL-6 increases with the increase in TNF-α concentration. It has also been shown that higher levels of IL-6 in the acute phase of stroke and on the first and seventh days, and TNF-α during onset, were associated with poorer early and late prognosis in patients treated with intravenous thrombolysis. A relationship was found between the level of IL-6 and TNF-α in the subacute AIS and the severity of the neurological deficit. It has been shown that the investigated biomarkers may be a prognostic factor in the treatment of thrombolytic AIS.
Glucocorticoids (GCs), which are secreted by the adrenal cortex, are important regulators in the metabolism of carbohydrates, lipids, and proteins. For the proper functioning of the body, strict control of their release is necessary, as increased GCs levels may contribute to the development of obesity, type 2 diabetes mellitus, hypertension, cardiovascular diseases, and other pathological conditions contributing to the development of metabolic syndrome. 11β-hydroxysteroid dehydrogenase type I (11β-HSD1) locally controls the availability of the active glucocorticoid, namely cortisol and corticosterone, for the glucocorticoid receptor. Therefore, the participation of 11β-HSD1 in the development of metabolic diseases makes both this enzyme and its inhibitors attractive targets in the pharmacotherapy of the above-mentioned diseases.
MicroRNAs (miRNAs) are short and noncoding RNA fragments that bind to the messenger RNA. They have different roles in many physiological or pathological processes. MicroRNA‐21, one of the first miRNAs discovered, is encoded by the MIR21 gene and is located on the chromosomal positive strand 17q23.2. MicroRNA‐21 is transcribed by polymerase II and has its own promoter sequence, although it is in an intron. It is intra‐ and extracellular and can be found in many body fluids, alone or combined with another molecule. It regulates many signalling pathways and therefore plays an important role in the cardiovascular system. Indeed, it is involved in the differentiation and migration of endothelial cells and angiogenesis. It contributes to the reconstruction of a myocardial infarction, and it can also act as a cellular connector or as an antagonist to cardiac cell apoptosis. By playing all these roles, it can be interesting to use it as a biomarker, especially for cardiovascular diseases.