A mini-review of X-ray photodynamic therapy (XPDT) nonoagent constituents' safety and relevant design considerations.

Conventional photodynamic therapy (PDT) has proved effective in the management of primary tumors and individual metastases. However, most cancer mortality arises from wide-spread multiple metastases. The latter has thus become the principal target in oncology, and X-ray induced photodynamic therapy (XPDT or PDTX) offers a great solution for adapting the PDT principle to deep tumors and scattered metastases. Developing agents capable of being excited by X-rays and emitting visible light to excite photosensitizers is based on challenging physical and chemical technologies, but there are fundamental biological limitations that are to be accounted for as well. In the present review, we have established eight major groups of safety determinants of NPs encompassing 22 parameters of clinical applicability of XPDT nanoparticulate formulations. Most, if not all, of these parameters can be accounted for and optimized during the design and development of novel XPDT nanoparticles.

[Early Invasive Strategy in Patients over 75 Years with Acute Coronary Syndrome. A Single Center Study].

OBJECTIVE: to assess the clinical status, comorbidities, complications, in-hospital mortality and its structure in dependence of age and type of acute coronary syndrome (ACS) in case of early invasive strategy of ACS management. MATERIALS AND METHODS: we included in this retrospective study data of all patients (n=1353) with ACS subjected to emergency and urgent myocardial revascularization in High Medical Technologies Center (Kaliningrad, Russia) in 2014-2016. Age of 984 patients was <75 (group 1) and of 369 >75 years (group 2). RESULTS: Mean age was 60±8.6 and 80.1±4.2 years, in groups 1 and 2, respectively. Anamnesis of group 2 patients was substantially burdened by myocardial infarction and stroke, they significantly more often had reduced left ventricular ejection fraction (EF), congestive heart failure, valve disorders, and atrial fibrillation. Patients of group 2 more frequently had severe manifestations of acute heart failure (AHF) and cardiogenic shock. Portions of patients with Killip class III were 5.9 and 11.4%, IV -2.1% and 9.1% in 1 and 2, respectively. Group 2 patients compared with those of group 1 had higher GRACE score and higher bleeding risk. In-hospital all-cause mortality was 3.1 and 10%, ST elevation myocardial infarction mortality - 2.6 and 9.5% in groups 1 and 2, respectively. Non-ST elevation myocardial infarction + unstable angina mortality (0.5%) did not differ between groups. Mortality from AHF (2 and 6.5%) and percutaneous coronary intervention complications (stent thrombosis and no-reflow) (0.5 and 2.4%) was significantly higher in group 2. AHF mortality was similar in patients with preserved and mid-range EF of both groups, but among those with reduced EF it was significantly higher in group 2 compared with group 1 (7.3 vs. 18.6%, respectively). There were no significant differences between groups in rates of gastro-intestinal and major bleedings. CONCLUSIONS: Clinical course of ACS was more severe in patients aged >75 years compared with patients aged <75 years. Early invasive strategy was effective irrespective of patient's age and ACS type. Rate of fatal outcomes due to complications of stenting and AHF were higher among very elderly patients. AHF more often caused death in very elderly patients with reduced EF. The rest of the structure of complications and mortality was similar in patients of different ages.

Methods to Assess the Antioxidative Properties of Probiotics.

Probiotics prove useful in correcting and preventing numerous health conditions, including those having severe impact on society, e.g., obesity and cancer. Notably, these capabilities of probiotics appear to be associated with their antioxidant properties. The mechanisms of antioxidant action of probiotics range from immediate biochemical scavenging of reactive substances to induction of signaling events leading to increased capacity of the host's cytoprotective systems. Since the antioxidant effects of probiotics significantly vary in types and details, a broad selection of methods of assessment of these properties is required in order to identify, characterize, and develop novel probiotics for medical purposes, as well as to explain the mechanisms of action of probiotics already in use in healthcare. This review revises the versatile toolbox, which can be used to assess the antioxidant properties of probiotics.

Mitochondria as a Signaling Hub and Target for Phenoptosis Shutdown.

Mitochondria have long been studied as the main energy source and one of the most important generators of reactive oxygen species in the eukaryotic cell. Yet, new data suggest mitochondria serve as a powerful cellular regulator, pathway trigger, and signal hub. Some of these crucial mitochondrial functions appear to be associated with RNP-granules. Deep and versatile involvement of mitochondria in general cellular regulation may be the legacy of parasitic behavior of the ancestors of mitochondria in the host cells. In this regard, we also discuss here the perspectives of using mitochondria-targeted compounds for systemic correction of phenoptotic shifts.

[The role of a lysine residue in the antioxidant and dna-protective activity of oligopeptides].

Oligopeptides present in the living cell were found to have antioxidative activity and to be involved in the regulation of antioxidant balance by interaction with the redox-dependent cellular signaling cascades. Experiments on animal models have shown that the introduction of oligopeptides causes geroprotective and adaptogenic effects. In the present work, we investigate the biological action of a number of synthetic oligopeptides using bacterial biosensors. This approach allows us to precisely estimate the antioxidant properties of the compounds without affecting their participation in regulatory cascades typical to eukaryotic cells. It has been shown that the ability of oligopeptides to protect cells from action of physical prooxidant factors (UV irradiation) is related to the presence of a lysine residue in the molecule. For chemical pro-oxidants (dioxidine), we have observed a similar, though less strict pattern. This effect also correlates with DNA-protective activity of the investigated oligopeptides.

Antimutagenic activity of mitochondria-targeted plastoquinone derivative.

The ability of cationic plastoquinone derivative 10-(6'-plastoquinonyl) decyltriphenylphosphonium (SkQ1) to modify processes of spontaneous and induced mutagenesis was studied. It is shown that daily introduction of this compound into male Wistar rats in doses of 25 and 250 nmol/kg during two weeks decreases spontaneous level of chromosome aberrations in anaphase in the eye cornea from 0.39 +/- 0.09 to 0.13 +/- 0.08 and 0.14 +/- 0.05, respectively. The level of 8-hydroxy-2'-deoxyguanosine in blood serum of the investigated animals decreases from 32.12 +/- 1.55 to 25.90 +/- 2.26 and 25.76 +/- 1.50 ng/ml, respectively. These facts indicate that the decrease in spontaneous clastogenesis is caused by decreased level of DNA damage by endogenous reactive oxygen species. A higher dose of SkQ1 also decreases to control level chromosome aberrations caused by oxygen under pressure of 0.5 MPa for 60 min. It is also shown in experiments with bacterial biosensors that SkQ1 is able to efficiently protect cells against genotoxic effect of UV radiation at 300-400 nm.