Predictive , Preventive , Personalized Medicine Research Articles

COMPARATIVE RISK-ORIENTED INTEGRATED ASSESSMENT OF LUNG HEALTH STATUS IN PREVENTIVE PLANNING OF REHABILITATION TREATMENT PROGRAMS IN A SANATORIUM

Introduction. COPD is a heterogeneous disease, the variability and diversity of which depends on a combination of genetics and risk factors. At present, during the period of the deciphered human genome, an earlier assessment of the prognostic risk of the development of cochlea in young people is needed to understand the possibilities of establishing reversible lung lesions. Aim as a part of preventive phenotyping in young people; substantiate the importance of a comparative risk-oriented complex epigenetic and genetic assessment of the lung health status for predictive assessment of the risk of developing COPD. Materials and methods. In this cohort study, 293 young people (11-23 years old) took part, including 142 male and 151 female, who were divided into four groups. 1st group - 132 conditionally healthy non-smokers (51 male and 81 female), 2nd - 54 conditionally healthy smokers (39 male and 15 female), 3rd - 86 non-smokers, with chronic lung diseases (52 persons – chronical tracheobronchitis; 43 persons – bronchial asthma), 4th - 21 smokers with chronic lung diseases (HRTB - 12 persons, BA - 9 persons). To assess the differences in epigenetic and genetic criteria, methods such as spirometry, gas analysis, electronic auscultation, digital acoustic analysis of respiratory work, analysis of gene polymorphisms for the alpha1-antitrypsin-SERPINA-1 complex in venous blood serum were used. We have developed a computer program, taking into account the risk factors for the prognostic development of COPD in a cohort of smoking and non-smoking young people aged 11-23 years with or without a diagnosis of chronic lung disease. Results. Among the most reliable, informative, sensitive and specific phenotyping indicators in assessing the prognostic degree of COPD risk in adolescents: cough, sputum production, ARI frequency per year, smoking index, electronic auscultation data, FEV1%, FVC%, FEV1 / FVC%, CO, O2, AAT, SERPINA. These criteria made up the characteristics of risk phenotypes, which allows the subjects to be graded according to groups (phenotypes) of the prognostic risk of COPD - low, moderate, high or extremely high, depending on the scale of criterion values. In young people in the context of predictive preventive personalized medicine. This made it possible to draw up an algorithm for assessing risk groups and a computer program based on this algorithm, which makes it possible to determine the phenotypes of COPD risk in young people. Conclusion: Starting from adolescence, it is possible to record the initial functional disorders of the respiratory status in combination with genetic polymorphisms, which confirms the need for preventive screening for the primary identification of risk groups and the formation of preventive programs in young people. The developed algorithm and computer program make it possible to determine the prognostic risk of COPD in young people - from low to moderate, high and extremely high, in terms of the implementation of the concept of 3P (personalized, preventive, and predictive) medicine.

Intestinal alkaline phosphatase modulation by food components: predictive, preventive, and personalized strategies for novel treatment options in chronic kidney disease.

Alkaline phosphatase (AP) is a ubiquitous membrane-bound glycoprotein that catalyzes phosphate monoesters' hydrolysis from organic compounds, an essential process in cell signaling. Four AP isozymes have been described in humans, placental AP, germ cell AP, tissue nonspecific AP, and intestinal AP (IAP). IAP plays a crucial role in gut microbial homeostasis, nutrient uptake, and local and systemic inflammation, and its dysfunction is associated with persistent inflammatory disorders. AP is a strong predictor of mortality in the general population and patients with cardiovascular and chronic kidney disease (CKD). However, little is known about IAP modulation and its possible consequences in CKD, a disease characterized by gut microbiota imbalance and persistent low-grade inflammation. Mitigating inflammation and dysbiosis can prevent cardiovascular complications in patients with CKD, and monitoring factors such as IAP can be useful for predicting those complications. Here, we review IAP's role and the results of nutritional interventions targeting IAP in experimental models to prevent alterations in the gut microbiota, which could be a possible target of predictive, preventive, personalized medicine (PPPM) to avoid CKD complications. Microbiota and some nutrients may activate IAP, which seems to have a beneficial impact on health; however, data on CKD remains scarce.

Infections of the lung: a predictive, preventive and personalized perspective through the lens of evolution, the emergence of SARS-CoV-2 and its pathogenesis.

The long evolutionary battle between humans and pathogens has played an important role in shaping the current network of host-pathogen interactions. Each organ brings new challenges from the perspective of a pathogen to establish a suitable niche for survival while subverting the protective mechanisms of the host. Lungs, the organ for oxygen exchange, have been an easy target for pathogens due to its accessibility. The organ has evolved diverse capabilities to provide the flexibility required for an organism’s health and at the same time maintain protective functionality to prevent and resolve assault by pathogens. The pathogenic invasions are strongly challenged by healthy lung architecture which includes the presence and activity of the epithelium, mucous, antimicrobial proteins, surfactants, and immune cells. Competitively, the pathogens in the form of viruses, bacteria, and fungi have evolved an arsenal of strategies that can over-ride the host’s protective mechanisms. While bacteria such as Mycobacterium tuberculosis (M. tuberculosis) can survive in dormant form for years before getting active in humans, novel pathogens can wreak havoc as they pose a high risk of morbidity and mortality in a very short duration of time. Recently, a coronavirus strain SARS-CoV-2 has caused a pandemic which provides us an opportunity to look at the host manipulative strategies used by respiratory pathogens. Their ability to hide, modify, evade, and exploit cell’s processes are key to their survival. While pathogens like M. tuberculosis have been infecting humans for thousands of years, SARS-CoV-2 has been the cause of the recent pandemic. Molecular understanding of the strategies used by these pathogens could greatly serve in design of predictive, preventive, personalized medicine (PPPM). In this article, we have emphasized on the clinically relevant evasive strategies of the pathogens in the lungs with emphasis on M. tuberculosis and SARS-CoV-2. The molecular basis of these evasive strategies illuminated through advances in genomics, cell, and structural biology can assist in the mapping of vulnerable molecular networks which can be exploited translationally. These evolutionary approaches can further assist in generating screening and therapeutic options for susceptible populations and could be a promising approach for the prediction, prevention of disease, and the development of personalized medicines. Further, tailoring the clinical data of COVID-19 patients with their physiological responses in light of known host-respiratory pathogen interactions can provide opportunities to improve patient profiling and stratification according to identified therapeutic targets.

Endothelial progenitor cells as the target for cardiovascular disease prediction, personalized prevention, and treatments: progressing beyond the state-of-the-art.

Stimulated by the leading mortalities of cardiovascular diseases (CVDs), various types of cardiovascular biomaterials have been widely investigated in the past few decades. Although great therapeutic effects can be achieved by bare metal stents (BMS) and drug-eluting stents (DES) within months or years, the long-term complications such as late thrombosis and restenosis have limited their further applications. It is well accepted that rapid endothelialization is a promising approach to eliminate these complications. Convincing evidence has shown that endothelial progenitor cells (EPCs) could be mobilized into the damaged vascular sites systemically and achieve endothelial repair in situ, which significantly contributes to the re-endothelialization process. Therefore, how to effectively capture EPCs via specific molecules immobilized on biomaterials is an important point to achieve rapid endothelialization. Further, in the context of predictive, preventive, personalized medicine (PPPM), the abnormal number alteration of EPCs in circulating blood and certain inflammation responses can also serve as important indicators for predicting and preventing early cardiovascular disease. In this contribution, we mainly focused on the following sections: the definition and classification of EPCs, the mechanisms of EPCs in treating CVDs, the potential diagnostic role of EPCs in predicting CVDs, as well as the main strategies for cardiovascular biomaterials to capture EPCs.

Сandidate SNP-markers of rheumatoid arthritis that can significantly alter the affinity of the TATA-binding protein for human gene promoters

Rheumatoid polyarthritis (RA) is an autoimmune disease with autoantibodies, including antibodies to citrullant antigens and proinflammatory cytokines, such as TNF-α and IL-6, which are involved in the induction of chronic synovitis, bone erosion, followed by deformity. Immunopathogenesis is based on the mechanisms of the breakdown of immune tolerance to its own antigens, which is characterized by an increase in the activity of T-effector cells, causing RA symptomatology. At the same time, against the background of such increased activity of effector lymphocytes, a decrease in the activity of a number of regulatory cells, including regulatory T-cells (Treg) and myeloid suppressor cells, is recorded. There is reason to say that it is the change in the activity of suppressor cells that is the leading element in RA pathogenesis. That is why only periods of weakening (remission) of RA are spoken of. According to the more powerful female immune system compared to the male one, the risk of developing RA in women is thrice as high, this risk decreases during breastfeeding and grows during pregnancy as well as after menopause in proportion to the level of sex hormones. It is believed that 50 % of the risk of developing RA depends on the conditions and lifestyle, while the remaining 50 % is dependent on genetic predisposition. That is why, RA fits the main idea of postgenomic predictive-preventive personalized medicine that is to give a chance to those who would like to reduce his/her risk of diseases by bringing his/her conditions and lifestyle in line with the data on his/her genome sequenced. This is very important, since doctors consider RA as one of the most frequent causes of disability. Using the Web service SNP_TATA_Z-tester (http://beehive.bionet.nsc.ru/cgi-bin/mgs/tatascan_fox/start.pl), 227 variants of single nucleotide polymorphism (SNP) of the human gene promoters were studied. As a result, 43 candidate SNP markers for RA that can alter the affinity of the TATA-binding protein (TBP) for the promoters of these genes were predicted.

Immunohistological staining of unknown chemokine RANTES/CCL5 expression in jawbone marrow defects\u2014osteoimmunology and disruption of bone remodeling in clinical case studies targeting on predictive preventive personalized medicine

BackgroundFatty degenerative osteonecrosis in the medullary spaces of the jawbone (FDOJ) may be identified as a lesser known source of RANTES/CCL5 (R/C) overexpression. The chemokine R/C also interferes with bone metabolism leading to osteolysis in areas affected by FDOJ. Many dental surgeries require functioning repair mechanisms and these may be disrupted by R/C overexpression.ObjectiveTo clarify the way in which R/C expression from adipocytes in FDOJ causes a disturbance in osteogenesis and impacts on medullary stem cells by investigating the detection of R/C expression with immunochemical staining.Materials and methodsWe examined the tissue samples of 449 patients with FDOJ to assess the level of the chemokine R/C using bead-based Luminex® analysis. In six clinical case studies of FDOJ, we compared bone density, histological findings, R/C expression, and immunohistochemical staining.ResultsR/C is overexpressed by up to 30-fold in the 449 FDOJ cases when compared with healthy jawbone samples. The comparison of the six clinical cases consistently shows greatly reduced bone density, (i.e., osteolysis), but varies in terms of the level of agreement across the other three parameters.DiscussionR/C from FDOJ sources may be implicated in several immune responses and considered a key pathogenetic pathway for increased adipogenesis rather than desirable osteogenesis. Adipocytes pathogenetically act via R/C expression in local FDOJ and systemically on the immune system.ConclusionR/C may be regarded as an important trigger for possible pathological developments in the fate of hematopoietic stem cells. FDOJ is not a rigidly uniform process but reflects changing stages of development. The absence of correlating findings should not be interpreted as a misdiagnosis. It seems appropriate to direct further research in the field of “maxillo–mandibular osteoimmunology” focusing on R/C overexpression in FDOJ areas. This may contribute to the development of personalized strategies in preventive medicine.

SNP_TATA_Comparator: genomewide landmarks for preventive personalized medicine.

Year after year, conditions, quality, and duration of human lives have been improving due to the progress of science, technology, education, and medicine, which however has a downside. Owing to improvement in children's nutrition, developmental acceleration occurs that imbalances a child's system. Because of virtual worlds of the Internet, social experience of teenagers expands and clashes with puberty of adolescents. Due to the comfort of cities, urbanization emerges and causes stress to adults because of artificial light, noise, pollution, violations of personal space, and family disruption. At old age, all these factors taken together contribute to loneliness, cancer, diabetes, drug addiction, and sporadic Alzheimer's disease, which shorten the lifespan, as reviewed in the US, 1990-2010. That is why, a person may ask oneself: "What can I do now to keep my health in my old age?" To help them, we provide this comprehensive review on predictive preventive personalized medicine. This branch of molecular medicine uses single nucleotide polymorphisms to prevent diseases on the basis of the difference between the individual and reference human genomes.

Biomedical and candidate SNP markers of chronopathologies can significantly change the affinity of the ТАТА-binding protein to the promoters of human genes

The computational analysis of millions of unannotated SNPs from the 1000 Genomes Project may speed up the search for biomedical SNP markers. We combined the analysis of SNPs at the binding sites of the TATA-binding protein (TBP) using a previously described Web service (http://beehive.bionet.nsc.ru/cgi-bin/mgs/tatascan/start.pl) with a keyword search for biochemical markers of chronopathologies that correspond to the clinical manifestations of these SNPs. We found 32 known and candidate SNP markers of circadian-rhythm disturbances in the [–70;–20] region of the promoters of 14 human genes (location of proven binding sites of TBP). These SNPs include rs17231520 and rs569033466 (both confer risk of chronopathologies in the liver); rs35036378 (behavioral chronoaberrations); rs549858786 (rheumatoid arthritis with a chronoaberration of IL1B expression); rs563207167, rs11557611, and rs5505 (all three: chronopathologies of the tumor—host balance, blood pressure, and the reproductive system); rs1143627 (bipolar disorder with circadian dependence of diagnosis and treatment); rs16887226 and rs544850971 (both: lowered resistance to endotoxins because of the imbalance between the circadian and immune systems); rs367732974 and rs549591993 (both: circadian dependence of heart attacks); rs563763767 (circadian dependence of myocardial infarction); rs2276109 and rs572527200 (both: circadian dependence of asthma attacks); rs34223104, rs563558831, and rs10168 (circadian optima of treatment with methotrexate and cyclophosphamide); and rs397509430, rs33980857, rs34598529, rs33931746, rs33981098, rs34500389, rs63750953, rs281864525, rs35518301, and rs34166473 (all: neurosensory hearing loss and restless legs syndrome). For these SNPs, we evaluated the α (significance) of changes in the affinity of TBP for promoters, where increased affinity corresponds to overexpression of the genes, and decreased affinity to deficient expression (Z-test). Verification of these 32 SNP markers according to the clinical standards and protocols may advance the field of predictive preventive personalized medicine.