[Influence of age of patients with bronchopulmonary pathology on low-molecular DNA concentration in blood plasma.]

The aim of the work was to determine the concentration of low-molecular-weight plasma DNA (lmDNA) in patients with COPD and chronic non-obstructive bronchitis (CnonB) of two age groups - 34-59 and 60-80 years. The levels of lmDNA in healthy donors, patients with CnonB, healthy relatives of patients with COPD did not differ, while the concentration of lmDNA in patients with COPD was significantly lower. In COPD patients aged 34-59 years, the level of lmDNA was reduced by more than 7 times, and in COPD patients who survived to 60-80 years, it was 3 times lower compared to the value of this biochemical indicator in healthy donors of the same age. The reduction of lmDNA reflected a reduced systemic apoptotic activity in the body of patients with COPD. A significant difference in the concentration of lmDNA in patients with COPD and CnonB in remission can be used for differential diagnosis of the development of these pathological processes. An increase in the low level of lmDNA in COPD patients during aging may indicate the involvement of epigenetic mechanisms in life extension.

Decellularized Extracellular Matrix for Tissue Engineering (Review).

In recent years, decellularized tissues have evolved into a new, full-fledged platform for the creation of tissue-engineered constructions. Extracellular matrix (ECM) of each tissue provides a unique tissue-specific microenvironment for resident cells with the structure and biochemical signaling required for their functioning. The decellularized ECM (dECM) has been established to influence cell differentiation. The review provides recent data on the composition and functions of the ECM, methods for obtaining decellularized tissues, and their application in tissue engineering depending on their physical form (scaffold, powder, or hydrogel). The effect of the matrix source, decellularization and sterilization techniques on dECM composition has been considered. Regulatory mechanisms of cell differentiation by the extracellular matrix are discussed. Differences in the protein composition of the native and decellularized materials are presented. Application of dECM in the bioink composition for regeneration of various tissues using bioprinting technologies is also considered. It has been concluded that successful application of dECM in tissue engineering and regenerative medicine requires a permanent and biologically suitable dECM source, optimized tissue decellularization protocols, improved mechanical properties of dECM-derived bioinks, and prevention of immunological reaction of the organism.

Biphasic aggregation of a perylene bisimide dye identified by exciton-vibrational spectra.

The quantum efficiency of light emission is a crucial parameter of supramolecular aggregates that can be tuned by the molecular design of the monomeric species. Here, we report on a strong variation of the fluorescence quantum yield due to different phases of aggregation for the case of a perylene bisimide dye. In particular, a change of the dominant aggregation character from H- to J-type within the first aggregation steps is found, explaining the observed dramatic change in quantum yield. This behaviour is rationalised by means of a systematic study of the intermolecular potential energy surfaces using the time-dependent density functional based tight-binding (TD-DFTB) method. This provides a correlation between structural changes and a coupling strength and supports the notion of H-type stacked dimers and J-type stack-slipped dimers. The exciton-vibrational level structure is modelled by means of an excitonic dimer model including two effective vibrational modes per monomer. Calculated absorption and fluorescence spectra are found to be in reasonable agreement with experimental ones, thus supporting the conclusion on the aggregation behaviour.

Toxicogenomic Effects in Rat Blood Leukocytes and Chemoprophylaxis of Radiation-Induced Carcinogenesis.

Toxicogenomic parameters were studied in the blood of female rats after exposure to ionizing γ-radiation in a dose of 4 Gy and chemoprophylaxis with α-difluoromethylornithine, eleutherococcus or leuzea extracts, which were used in animals with morphological manifestations of tumor growth under conditions of radiation-induced carcinogenesis. Life-time evaluation of toxicogenomic effects was carried out by express method for measurements of blood nucleotid DNA - fluorescent indication. The level of hyperaneu/polyploidy increased in the blood leukocytes of control rats 30 days after radiation exposure. A significant decrease of genotoxicity as a result of drug treatment in comparison with the number and multiplicity of tumors in irradiated animals was found only in the endocrine and reproductive organs of rats treated by eleutherococcus extract.

Blood DNA radiosentivity as a predictive bindex of radiochemical treatment efficacy in cervical cancer patients.

Study of cervical cancer patients with I-III stage was performed with biomarker determination of the blood DNA radiosensitivity ex vivo. The biochemical index was measured before treatment start during 4 hours by use fluorescent dye. The relationship between changes of these index levels and volume tumor reductions after radiochemical treatment evidenced that blood DNA radiosensitivity was enabled to predict an outcome of the cervical cancer patient treatment earlier than the assessment of therapy efficacy by help of ultrasound measurements.

Peculiarities of measuring ion energy distribution in plasma with a retarding field analyzer.

Presented are the results from tailoring the retarding field energy analyzer to measure the degree of charge compensation and regular patterns in the separations of ions of different mass, with the multicomponent ion flow spreading out in the plasma-optical mass separator model.

Effects of iron ions and iron chelation on the efficiency of experimental radiotherapy of animals with gliomas.

We evaluated the effect of iron ion chelation on the growth of gliomas and radiotherapy efficiency in tumor-bearing animals. The rats with transplanted glioma-35 received iron-containing water; desferroxamine was injected for metal chelation. Long-term treatment with iron-containing water promoted glioma growth in rats and improved the efficiency of radiotherapy due to combination of apoptosis and ferroptosis. Desferroxamine reduced the efficiency of this treatment and was inessential for the efficiency of radiotherapy alone.

[Blood DNA Radiosensitivity May Be Predictive Marker for Efficacy of Radiation Therapy in Glioma Tumorbearing Individuals].

Animal and clinical studies were conducted to evaluate the association between the blood DNA radiosensitivity, assessed by determining the original S-index ex vivo, and the response of gliomas to irradiation in vivo. Possible modifications of the latter after administration of iron-containing water (ICW) in rats were also explored. The study was performed on the rats with subcutaneously implanted experimental glioma-35. The tumors were locally X-irradiated with a single 15 Gy dose as a radiation therapy (RT). ICW (60-63 mg · Fe 2+/l) was administered as a drinking water for 3 days before treatment. The animals underwent blood sampling for analysis of the DNA concentration and leukocyte count. The DNA index was estimated 24 h after RT. The S-index was evaluated within 4 h before RT. The mean initial S-index in the blood samples of glioma-bearing rats was 0.73 ± 0.05. Addition of ICW ex vivo resulted in a significantly increased S-index in a half of the samples. In general, the irradiated rats, which had been given pretreatment with ICW and demonstrated an ex vivo increase of the S-index to > 1.0, showed the most marked inhibition of tumor progression and the smallest tumor volume 25 days after irradiation. They also exhibited the lowest rate of growth and the longest survival. Determination of the biochemical S-index and evaluation of its changes ex vivo caused by ICW may be predictive of the response of experimental glioma to irradiation with radiomodification. The S-index may serve as a predictive indicator in clinic of the efficient evaluation of RT in patients with glioma.

[DNA POLYMORPHISM AND RISK OF OCCLUSIVE VASCULAR LESIONS IN PATIENTS WITH CARDIOVASCULAR DISEASES].

A method for diagnostics of occlusive vascular lesions in patients with cardiovascular diseases is proposed. Results of this study extend possibilities for diagnostics of occlusive vascular lesions in patients with cardiovascular diseases.

[Predicting of the effectiveness of radiotherapy and chemoradiotherapy for cancer patients].

Studies carried out on samples of tumor and non-tumor tissue indicate that markers of radiosensitivity for predicting individual patient response to the planned radiation therapy may be the indicators of apoptosis and molecular profiles read from the DNA of patients. At present there is developed a technology for rapid and economical determining of indicators for the reasonable use of radiation therapy in the radiological practice in patients with breast cancer, bladder cancer and malignant glioblastomas by means of an evaluation of radiosensitivity of the DNA of blood.

[Personalized treatment of tumor-bearings after prediction of radio and chemoradio-therapy efficacy by means of blood DNA radiosensitivity].

Ongoing studies on the tumor and non-tumor samples carried out worldwide give evidence that some apoptotic indexes, DNA-based microarray molecular profiling analysis as well as determination of single nucleotide polymorphisms in the genome of a patient's tumor can serve perspective markers of radiosensitivity for the response prediction in individual patients to intendedradiation therapy. Over the last years there has been an increasing interest in radiogenomic and characterization of DNA array molecular profiles that can predict the response to irradiation in tumor and non-tumor tissues. Now a technology of the short-term and inexpensive determination of indices aimed at an objectively based use of radiation therapy in experiment or clinic after evaluation of blood DNA radiosensitivity has been developed.

[Effects of iron ion additional introduction in radiation therapy of tumor-bearing animals].

The gender differences of the transplantable glioma-35 growth were revealed in tumor-bearing rats. The effect of mineral iron containing water (ICW) as drinking water was studied during radiation therapy (RT) in tumor bearing male rats. It was shown that ICW used separately had a weak anti cancer effect. The ICW use after irradiation caused no significant changes in hematological reactions as compared with RT only. The mineral water administration before irradiation resulted in the reduction of the supercoiled DNA index on the 1st and 21st day after irradiation, as well as in monocytopeny and a definite decrease in the tumor volume on the 21st day of the experiment as compared with control, which is associated with the ferroptosis effect of ICW. It was established that the reaction peculiarities of the blood DNA structure index in irradiated rats at the early stage of glioma growth may serve an express marker of the efficiency of RT.

[Comparative effects of difluoromethylornithine and tincture of Siberian ginseng root on radiation carcinogenesis and life span in rats].

Influence of alpha-difluoromethylornithine (DFMO) and tincture of Siberian ginseng root (TSGR) on radiation carcinogenesis and life span in rats has been studied. The results of the study demonstrate that DFMO as well as TSGR significantly improved survival and decreased incidence and multiplicity of malignant and benign tumors in rats subjected to ionizing radiation. Beneficial effect on the rat survival rate and anticarcinogenic action of DFMO were more expressed compared with TSGR.

[Inhibitory effect of bioginseng on radiation-induced carcinogenesis in rats].

Influence of bioginseng (biotechnological pharmaceutical drug from ginseng radix culture) on radiation-induced carcinogenesis has been studied. LIO female rats were divided into 3 groups. Rats of the first group (n=25) were used as intact control and weren't exposed to any influence. Rats of the second (n=50) and third (n=50) groups were exposed to single total body gamma-irradiation at a dose of 4 Gy. Animals of the 2nd group weren't exposed to any influence after irradiation, while animals of the 3rd group were given bioginseng with tap water (20 ml/l) until the end of study (438 days). In the control group 22,7% of animals developed tumors. In the 2nd group (irradiated control) 70% of animals were bearing multiple tumors one third of which were malignant. Mammary gland tumors were most frequent. Compared to the 2nd group the 3rd group receiving irradiation and bioginseng demonstrated the decrease in tumor incidence by 24.5% and 2,4 rate of decrease in tumors number. For the malign tumors was observed the decrease by 26.8% and 2,9 times, accordingly. For the mammary tumors the decrease was by 23.0% and 2,0 times, for mammary adenocarcinomas by 23.4% and 3,5 times, accordingly. The incidence and number of endocrine and reproductive organs tumors was 20,9% and 5,6 times, accordingly. Therefore, bioginseng effectively inhibits carcinogenesis induced by ionizing radiation in female rats.

[Biochemical markers predicting response to radiation- and radiochemo-therapy in cancer patients].

In last years there is increasing interest in radiogenomics and the characterization of DNA array molecular profiles that can predict tumor and no tumor tissues radioresponse. Ongoing studies carried out worldwide in the banking of tumor and no tumor samples give evidence that perspective markers for response prediction in individual patient to intended radiation therapy can be some apoptotic indexes, spectrum a number of specific proteins, and DNA-based microarray molecular profiling analysis as well determination of single nucleotide polymorphisms in genome of the patients. So far there are only a few robust reports of molecular markers predicting tumor and no tumor tissues response to radiation. The results of new studies, which in future should be validated in larger definitive trials, are likely to see in nearest years. It is needed to determine technologies of methods and to define more precisely areas of its applications.

Hematological and toxicogenomic effects of ferromagnetic screening of natural electromagnetic fields.

Aftereffects of ferromagnetic screening on the hematological and toxicogenomic parameters in rats were traced over 45 days. Two-day ferromagnetic screening of male and female rats (reducing permanent constituent of magnetic field induction by 4-10 µT) led to leukopenia observed on day 14 of the experiment. Life-time evaluation of the toxicogenomic effects was carried out by rapid method for measurement of blood nucleotide DNA by fluorescent indication. In male blood leukocytes, increased aneuploidy and polyploidy were observed after 48 h of ferromagnetic screening and remained high on days 12 and 28 after screen removal. In contrast to males, leukocyte apoptosis in females was increased only 48 h after the start of ferromagnetic screening.

[Effect of additional administration of ferric ion on the life span of irradiated animals].

There were established regularity of early biological reactions, restoration and life span shortening in rats after gamma-irradiation of animals with low (25 and 50 cGy) or 600 cGy doses in combination with various regimen of ferric ions introduction with drinking water (60-63 mg/l).

[The influence of ferromagnetic screening from natural electromagnetic fields on the hematological and toxicogenomic indexes in animals].

The aim of the study was to reveal during 45 days consequences of ferromagnetic screening (FS) on the hematological and toxicogenomic indexes in rats. An express-method of nucleiod DNA content in blood by help fluorescent indication was used for alive quantitative evaluation of the toxicogenomic effects. The FS for both gender rats during 48 hrs resulted in both decreased magnetic field by 4-10 microT1 and leucopenia by 14 day of experiment. The aneu-/polyploidy index in male leucocytes was increased by 48 hr of FS and lasted out to 12-28 days after the screen removal. The leukocyte apoptosis was enhanced in female in 48 hrs only after the FS start.

[Effect of additional administration of iron ions on the efficacy of radiotherapy of glioma-bearing animals].

Our analysis failed to establish any antitumor effect of treatment of rats with transplantable glioma-35 with iron-containing mineral drinking water (ICMW). The latter treatment combined with irradiation (15 Gy) was followed by enhanced genotoxic effect in white blood cells. Post-irradiation administration of ICMW did not influence glioma growth significantly as compared with radiation alone. Pre- and post-iradiation drinking of ICMW resulted in marked leukopenia 24 hrs after exposure as well as to significant decrease in tumor size (20-40 days after of experiment) as compared with control.