Search

Gene expression is regulated and tightly controlled by epigenetic mechanisms. Alterations of these mechanisms are frequently observed in various diseases, particularly, in various types of cancer. Malignant transformation is caused by the impairment of the mechanisms of cell differentiation and cell cycle control associated with epigenetic changes. Altered patterns of epigenetic modification associated with malignancies can potentially be reversed by some agents that act on the key proteins responsible for DNA/histone modification and chromatin remodelling. Examples of such substances include the inhibitors of DNA methyltransferases or histone deacetylase. During the recent years, a number of such substances have been evaluated as potential therapeutic agents against certain types of cancer in preclinical and clinical studies, and some of them have been approved for treatment of hematological cancers. Application of epidrugs for therapy of solid tumors remains, however, more challenging. In this review, we summarize the current knowledge on the most studied mechanisms of epigenetic modification and the available epigenetically active drugs.

Atherosclerosis is a lipoprotein-driven inflammatory disorder leading to a plaque formation at specific sites of the arterial tree. After decades of slow progression, atherosclerotic plaque rupture and formation of thrombi are the major factors responsible for the development of acute coronary syndromes (ACSs). In this regard, the detection of high-risk (vulnerable) plaques is an ultimate goal in the management of atherosclerosis and cardiovascular diseases (CVDs). Vulnerable plaques have specific morphological features that make their detection possible, hence allowing for identification of high-risk patients and the tailoring of therapy. Plaque ruptures predominantly occur amongst lesions characterized as thin-cap fibroatheromas (TCFA). Plaques without a rupture, such as plaque erosions, are also thrombi-forming lesions on the most frequent pathological intimal thickening or fibroatheromas. Many attempts to comprehensively identify vulnerable plaque constituents with different invasive and non-invasive imaging technologies have been made. In this review, advantages and limitations of invasive and non-invasive imaging modalities currently available for the identification of plaque components and morphologic features associated with plaque vulnerability, as well as their clinical diagnostic and prognostic value, were discussed.

Chronic obstructive pulmonary disease (COPD) is a multifactorial disease, in which systemic inflammation plays a key role. This 6-month randomized double-blinded placebo-controlled study evaluates the possible effect of natural preparation Inflaminat on clinical symptoms of COPD, indicators of respiratory function, and exacerbation frequency in 60 patients with moderate severity of COPD. Inflaminat is a combination of natural ingredients black elder (Sambucus nigra L.) berries, violet (Viola tricolor L.) herb, and calendula (Calendula officinalis L.) flowers. The preparation has been previously demonstrated to possess anticytokine and anti-inflammatory effects in experimental studies. In present study, COPD dynamics were evaluated by means of BCSS (Breathlessness, Cough, and Sputum Scale) and spirometry tests. It was shown that 6-months Inflaminat administration led to significant decrease of BCSS points from 3.0 &plusmn, 0.6 to 1.9 &plusmn, 0.7, (p = 0.002) as well as significant increase of FEV1 from 66 &plusmn, 18% to 73 &plusmn, 17%, (p = 0.042), there were no beneficial dynamics in placebo group. Side effects associated with preparation administration were not identified. The results of the study suggest that Inflaminat may be employed in treatment of patients with moderate severity of COPD, since it has a positive effect on COPD symptoms according BCSS and indicators of respiratory function FEV1.

This randomized double-blinded, placebo-controlled clinical trial evaluated the progression of intima-media thickness of common carotid artery (cIMT) and the effect of phytoestrogen therapy on atherosclerosis development in early and late postmenopausal women. The 2-year cIMT progression was evaluated in 315 early postmenopausal women aged 40−55 years and in 231 late postmenopausal women aged 60−69 years free of cardiovascular disease. B-mode ultrasound was done at baseline and after 12 and 24 months of follow-up. The study revealed no significant changes in the rate of cIMT progression in 315 early postmenopausal women. By contrast, a statistically significant difference in the rate of atherosclerosis development was observed in late postmenopausal women treated with phytoestrogens compared to placebo (p = 0.008). The rate of cIMT progression in the placebo group was 0.019 mm/year led to a significant increase of cIMT during the observation period (p = 0.012), while the rate of cIMT progression in phytoestrogen late postmenopausal recipients was 0.011 mm/year, and total change did not reach statistical significance during the follow-up period (p = 0.101). These results suggest that late postmenopausal women can be a suitable cohort for trials assessing the anti-atherosclerosis effects of phytoestrogen preparations. In particular, the beneficial effect of phytoestrogens on cIMT progression was demonstrated in late postmenopausal women.

Background: Salidroside, one of the main active ingredients in Fructus Ligustri Lucidi (FLL), is well demonstrated to exert anti-osteoporotic effect. However, the plasma pharmacokinetic profile of salidroside in FLL in estrogen-deficient rats remains unknown. Objective: The objective was to develop a sensitive, rapid, and accurate ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) method for the determination of the pharmacokinetics profile of salidroside after oral administration of FLL aqueous extract in normal and ovariectomized (OVX) rats. Materials and Methods: OVX and normal rats were orally administrated with FLL at a bolus of 7 g/kg. Plasma samples were precipitated by methanol, and the supernatant was chromatographed by a Waters BEH C18column with a gradient elution of ammonium acetate and acetonitrile. Quantification was carried out on the electrospray ionization, positive multiple reaction monitoring modes. Results: The lower limit of detection was 50 ng/mL, and the dynamic linear range was 50–30,000 ng/mL with a value of R2 > 0.99. The intra- and inter-day precisions were lower than 14.67%, and accuracy was in the range of 99.29%–103.37%. The recovery of salidroside ranged from 88.90% to 101.78%, with the matrix effect ranging from 85.53% to 100.45%. The t1/2, MRT0–∞, and apparent volume of distribution for salidroside increased in OVX rats. Conclusion: A sensitive, accurate, and rapid method was successfully established and validated for the determination of plasma characteristics of salidroside in Sprague–Dawley (SD) rats. The results suggest that ovariectomy could interfere with salidroside metabolism in SD rats.

Atherosclerosis is a chronic arterial disease characterized by vascular inflammation, accumulation of lipids in the arterial wall, and formation and growth of atherosclerotic plaques followed by ischemia. In subclinical atherosclerosis, cholesterol retention in subendothelial cells leads to induction of local inflammation, generation of foam cells and lesion formation, followed by a chain of other pathogenic events. Atherosclerotic progression can frequently be fatal, since plaque rupture may lead to thrombosis and acute events, such as myocardial infarction, stroke and sudden death. Traditional anti-atherosclerotic therapy is mainly focused on improving the blood lipid profile and does not target various stages of plaque progression. Obviously, treating the disease at initial stages is better than beginning treatment at advanced stages and, in that regard, current atherosclerosis management can be improved. Cholesterol retention is an important component of atherogenesis that precedes plaque formation. Therapeutic targeting of cholesterol retention may be beneficial for preventing further atherogenic progression. For this purpose, we suggest using herbal preparations due to good tolerability and suitability for long-lasting treatment. We developed test systems based on cultured human intimal aortic cells for rapid screening of potential anti-atherogenic drugs. With the help of these test systems, we selected several natural substances with significant anti-atherogenic activity and further use these compounds to prepare herbal preparations for anti-atherosclerotic therapy. These preparations were clinically tested and showed good safety and a potent anti-atherogenic potential.