[Modern approaches to studying the molecular mechanisms of lung functioning in normal and pathological conditions].

Problems with breathing and lung function are caused by the development of various lung diseases associated with lifestyle, harmful environmental factors and genetic predisposition. Knowledge of the molecular mechanisms of the development of the pathological process will allow on time identification of the disease or the development of targeted therapy. The article provides an overview of modern methods that make it possible to most accurately reproduce the structural, functional and mechanical properties of the lung (organ-on-a-chip), to perform non-invasive molecular studies of biomarkers of bronchopulmonary pathology using saliva diagnostics, as well as using DNA and RNA aptamers, verify tumor markers in biological samples of human tissue.

[Caldesmon and tumor growth: prospects for optimizing diagnosis and targeted therapy].

Tumor invasion plays a key role in the progression of tumors. This process is regulated by the interactions of cells and tissues, in which physical, cellular and molecular determinants undergo changes throughout the entire period of progression of tumor growth. Tumor invasion is triggered and maintained by specialized signal cascades that control the dynamic state of the cytoskeleton in tumor cells, the processes of rearrangement of cell-matrix and intercellular connections, followed by cell migration to neighboring tissues.

[Slowdown of replicative aging of fibroblasts by hyaluronan complexes with gold nanoparticles.].

Determination the activity of the genes of sirtuin-1, hyaluronidase, TGF-β cytokine, calreticulin in the process of replicative aging of human fibroblasts in vitro and the effect of hyaluronan preparations with gold nanoparticles on the activity of replicative cell aging. Compared the expression of proteins of the studied genes using specific markers at 7 and 14 passages of cultivation of fibroblasts isolated from human skin, without drugs and in the presence of drugs in the growth medium. This work shows a decrease in the activity of the sirtuin 1 gene and an increase in the expression of hyaluronidase in the process of replicative aging of human fibroblasts.

[Investigation of signal molecules in saliva: prospects of application for diagnostics of myocardial infarction and the aging rate of different age people.].

Among the diseases of the cardiovascular system in elderly people, ischemic heart disease and myocardial infarction (MI) occupy the first place in the structure of mortality. One of the main causes of disability and death from MI is late diagnosis. In this regard, the search for new, highly informative and non-invasive methods for diagnosing MI is an important task of molecular gerontology.

[The personalized medicine and organization of geriatric care of population].

The article presents advisability of applying approaches of personalized medicine to solve problems of modern gerontology and geriatrics. The actuality of issue is conditioned by population aging due to rapid increasing of both percentage and absolute number of elderly people in total population of most countries. The ideology of personalized medicine or P4 medicine is targeted to developing individual preventive and therapeutic activities for specific personality.

Spinal cord tissue affects sprouting from aortic fragments in ex vivo co-culture.

It is a well-known fact, that there is a close interconnection between vascular and neural structures in both embryonic development and postnatal life. Different models have been employed to dissect the mechanisms of these interactions, ranging from in vitro systems (e.g.

Primary culture of mouse embryonic spinal cord neurons: cell composition and suitability for axonal regeneration studies.

Primary culture is an effective experimental model to study molecular mechanisms that drive axonal regeneration after central nervous system injury. However, the culture of spinal cord (SC) cells remains poorly characterized. Here, we have analyzed the cell composition of a primary SC culture during its maturation.

Retinoic acid co-treatment aggravates severity of dioxin-induced skin lesions in hairless mice via induction of inflammatory response.

Exposure to toxic halogenated polyaromatic hydrocarbons, of which 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is the most potent, induces diverse skin pathologies in humans, including chloracne, hyperkeratosis, hamartomas, etc. While the toxic effects of TCDD have been extensively studied, effective approaches to their treatment are still lacking. Retinoids are commonly used in therapy of acneiform skin diseases.

[Molecular markers of Alzheimer disease early diagnostic: investigation perspectives of peripheral tissues.].

Alzheimer's disease (AD) is a progressive neurodegenerative disorder of elderly and old age people. For intravital diagnosis of the expression of signaling molecules - AD markers, cerebrospinal fluid (CSF) and peripheral tissues are used: lymphocytes and blood platelets, buccal and olfactory epithelium, skin fibroblasts. There are several changes in the production of hyper phosphorylated form of τ-protein, BACE1 and peptide Аβ42 in CSF in case of AD, but CSF taking may have a number of side effects.

First results of the double-blind randomized placebo-controlled multicenter clinical trial of DIM-based therapy designed as personalized approach to reverse prostatic intraepithelial neoplasia (PIN).

Background: Targeted pharmacological correction is used extensively in medical practice today. 3,3'-Diindolylmethane (DIM) is known as a substance with various anticancer properties. An interim study of the efficacy of a new drug Infemin on the basis of diindolylmethane (DIM) with improved bioavalability has been conducted.

Morphofunctional and signaling molecules overlap of the pineal gland and thymus: role and significance in aging.

Deficits in neuroendocrine-immune system functioning, including alterations in pineal and thymic glands, contribute to aging-associated diseases. This study looks at ageing-associated alterations in pineal and thymic gland functioning evaluating common signaling molecules present in both human and animal pinealocytes and thymocytes: endocrine cell markers (melatonin, serotonin, pCREB, AANAT, CGRP, VIP, chromogranin А); cell renovation markers (p53, AIF, Ki67), matrix metalloproteinases (MMP2, MMP9) and lymphocytes markers (CD4, CD5, CD8, CD20). Pineal melatonin is decreased, as is one of the melatonin pathway synthesis enzymes in the thymic gland.

Double-blind randomized placebo-controlled multicenter clinical trial (phase IIa) on diindolylmethane's efficacy and safety in the treatment of CIN: implications for cervical cancer prevention.

Background: The article presents the results of a clinical trial on the efficacy and safety of a novel pharmaceutical composition in the form of vaginal suppositories containing diindolylmethane in the course of cervical intraepithelial neoplasia (CIN) I-II conservative treatment. It offers an attractive drug therapy for more personalized prevention of cervical cancer.

Methods: A total of 78 women of reproductive age were included.

Chitosan as a Modifying Component of Artificial Scaffold for Human Skin Tissue Engineering.

We compared the structure and mechanical properties of scaffolds based on pure collagen, pure chitosan, and a mixture of these polymers. The role of the composition and structure of scaffolds in the maintenance of cell functions (proliferation, differentiation, and migration) was demonstrated in two experimental models: homogeneous tissue analogues (scaffold populated by fibroblasts) and complex skin equivalents (fibroblasts and keratinocytes). In contrast to collagen scaffolds, pure chitosan inhibited the growth of fibroblasts that did not form contacts with chitosan fibers, but formed specific cellular conglomerates, spheroids, and lose their ability to synthesize natural extracellular matrix.

Safety and tolerability of DIM-based therapy designed as personalized approach to reverse prostatic intraepithelial neoplasia (PIN).

Background: It has been shown previously that novel formulation of 3,3'-diindolylmethane (DIM) substance with high bioavailability (Infemin) inhibits tumor development due to the tumor growth rate reduction in the xenograft model of prostate cancer. Prostatic intraepithelial neoplasia (PIN) is considered to be promising as a personalized and preventive treatment strategy of prostate cancer (PC). We assessed the safety of Infemin in men with PIN and discussed the interim results.

Preclinical antitumor activity of the diindolylmethane formulation in xenograft mouse model of prostate cancer.

Aim: Preclinical study of the specific anticancer pharmacological activity of the formulation containing active substance 3,3ʹ-diindolylmethane (DIM), cod liver oil, polysorbate 80 and α-tocopherol acetate (vitamin E), in vivo in a xenograft animal model of LNCaP.

Materials And Methods: The DIM, cod liver oil, polysorbate 80 and α-tocopherol acetate (vitamin E) formulation was intragastrically administered to BALB/c-nude (nu/nu) mice during 33 days post inoculation at the dose of 133 mg/kg/day. Antitumor activity of the test drug was estimated by the rate of tumor growth inhibition (T/C% - treated versus control), dividing the tumor volumes from treatment groups with the control groups.

[Development of national and international standards of population age distribution for medical statistics, health-demographic analysis and risk assessment].

The current European standard (CES) and the World population age distribution standard is widely used in medical and demographic studies, performed by international (WHO, etc.) and national organizations. The Russian Federal Service of States Statistics (RosStat) uses CES in demographic yearbooks and other publications.

Comparative preclinical pharmacokinetics study of 3,3'-diindolylmethane formulations: is personalized treatment and targeted chemoprevention in the horizon?

Background: 3,3'-Diindolylmethane (DIM) is known as an agent of natural origin that provides protection against different cancers due to the broad spectrum of its biological activities in vivo. However, this substance has a very poor biodistribution and absorption in animal tissues. This preclinical trial was conducted to evaluate the pharmacokinetics and bioavailability of various DIM formulations in animal model.

[Proteomics as a fundamental tool for subclinical screening, tests verification and assessment of applied therapy].

Proteomics is a science which studies proteins of the body, interactions of proteins and their biological functions. Today, it is an essential partner in establishing preclinical diagnosis protocols. In conjunction with other sciences such as genomics and bioinformatics it will be possible to diagnose diseases on the earliest stages before its clinical onset or to gain the dynamics of pathological processes in the body and response to drug therapy.

[Introduction into PPPM: experience of the past and tomorrow's reality].

Health service today is on the verge of broad changes. The intensive practical application of the achievements of genomics, proteomics, metabolomics and bioinformatics has significantly deepened and continues to deepen our view of the pathological processes taking place at a level of biostructures. In the nearest future this progress will give medical practitioners the opportunity to focus on a subclinical stage of the disease, i.

[The Russian and international standards of age-related allocation of population for medical statistics, medical demographic analysis and risk assessment].

The actual European standard of age-related allocation of population in action is largely implemented in medical demographic studies of international (WHO etc.) and national organizations. The Rosstat also implements this standard in its demographic yearbooks and other publications.

Introduction into PPPM as a new paradigm of public health service: an integrative view.

In the present state of healthcare, usual medical care is generally given to the already diseased person, while the key link-personal health monitoring underlain by predictive, preventive, and personalised medicine (PPPM) techniques that are being intensively elaborated worldwide-is simply missing. It is this link, based on the recognition of subclinical conditions, prediction, and further preventive measures, that is capable of regulating morbidity and diminishing the rates of disability among able-bodied population, thus significantly cutting the traditionally high costs of treating the already diseased people. To achieve the above-mentioned goal-the elaboration of the PPPM concept and its practical implementation-it is necessary to create a fundamentally new strategy based upon the subclinical recognition of the signs-bioindicators of cryptic abnormalities long before the disease clinically manifests itself.

[Neuroimmunoendocrine mechanisms of regulation of reproductive function].

Modern molecular biological studies have significantly improved understanding of structural and functional organization of the female reproductive system. The paper gives a brief overview of the literature and own research on verification and expression in the endometrium and placenta of many peptides, biogenic amines, steroids, cytokines and other signalling molecules, which, acting as hormones, enzymes, inhibitors, receptors, growth factors, immunoregulatory agents, transport's and binding proteins, provide the local regulation of intercellular neuroimmunoendocrine relationships that play a key role in the mechanisms of human embryogenesis and reproduction.

[Refutation of traditional views of the disease and formation of the scientific basis of pathology (17-19th centuries)].

This paper focuses on the revision of disease concepts that prevailed during the Galenism era and the formation of the scientific basis of pathology at the time of two scientific revolutions of the 17-19th centuries.