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In this paper, we discuss what biomarkers to choose if there is a need to describe the results of laser therapy targeting keloid skin. We elevate the known cytomarkers (Krt14, Lgals7, Krt5, Dcn, Lum, Igfbp5, Cd31, Vwf, Stambpl1, Uqcrb, Cd3 and Acta2), biomarkers of the inflammatory response (Cd45/Ptprc, Adgre1, Ly6g, Il1b, Il4, Il13, Il22, Cxcl2 и Ccl17), as well as the proteins of extracellular matrix (type I and III collagens; precursors of COL5A1 and COLA1A; FTL, COL3A1, PGLS, CNN2, ANXA2, TPSAB1, COL12A1, precursors of APCS and ALB), and their encoding genes (FGF7, BAX, CCND1, MMP3, MMP9, CXCL1, -2, -5, -6 and -12; IL8, S100A7 and IL1A), those expression and co-location may potentially change the appearance and internal structure of damaged skin. We also describe how to choose biomarkers using the results genomic studies and their limitations. Moreover, we provide examples of how different groups of gene and protein biomarkers are used in experimental biology and clinical practice. According to the previously published data, well-known biomarkers verified on animal models, depend on their biological effects, let to characterize structural changes and changes in the composition of cells represented at the site of damage before and after the treatment. In addition, the published experimental and clinical data provide an opportunity to analyze the efficiency of new experimental approaches and compare them to each other.

The perturbed mK(3,1) equation is restudied to further explore the dynamics of solitary wave solutions by combining the geometric singular perturbation theorem and bifurcation analysis in this paper. Besides the solitary waves presented in literature [1–3], we show that this equation possesses a family of solitary waves which decay to some constants determined by their wave speeds and a parameter. It is shown that a portion of the solitary wave solutions to the mK(3,1) equation will persist under small perturbations and the wave speed selection principle is presented as well. In addition to the solitary waves, each of which has only one crest or trough and approximates to a solitary wave of the unperturbed equation as the perturbation parameter tends to zero, we theoretically prove the existence of a new type of solitary waves with coexisting crest and trough. The numerical simulations are carried out, and the results are in complete agreement with our theoretical analysis.

The decomposition problem for the control systems with singular perturbations is considered in the paper. A global invariant manifolds of slow motions are applied to show that the system under considferation can be reduced to two subsystems of the lower dimension. A two-link horisontal manipulator model is considered to illustrate the mathematical results. In contradictory to the works of other authors, asymptotic expansions are used for the approximate construction of splitting transformations, and not for solving initial or boundary value problems.

1AbstractThe testing of pharmacological hypotheses becomes faster and more accurate, but at the same time more difficult than even two decades ago. It takes more time to collect and analyse disease mechanisms and experimental facts in various specialized resources. We discuss a new approach to aggregating individual pieces of information about a single disease using Elsevier’s automated text mining technology. Developed algorithm allows for the collection of published facts in a unified format starting only with the name of the disease. The special template, which combines research and clinical descriptions of diseases was developed. The approach was tested, and information was collected for 55 rare monogenic diseases. Clinical, molecular, and pharmacological characteristics of diseases with supporting references from the literature are available in the form of tables and files. Manually curated templates for 10 rare diseases, including top ranked Cystic Fibrosis and Huntington’s disease, were published to demonstrate the results of the described approach.

107 patients (34 female and 73 male) diagnosed with “generalized psoriasis vulgaris, exudative form, progressive stage” were evaluated for the levels of anxiety and depression. These measurements were carried out along with psychiatrist interview, taking into consideration anamnestic and status information. 67,3% of patients unhesitatingly marked that a previous psychological trauma had caused the current exacerbation of psoriasis. The study reveals interrelationship between the psychiatric and somatic components of psoriasis. We managed to reach marked remission in 19 patients using low doses of psychotropic drugs along with primary dermatological treatment.

A previously developed model for mono-component droplet evaporation is revisited using new mathematical tools for its analysis. The analysis is based on steady-state mass, momentum, and energy balance equations for the vapor and air mixture surrounding a droplet. The previously obtained solution to these equations was based on the assumption that the parameter ε (proportional to the squared ratio of the diffusion coefficient and droplet radius) is equal to zero. The analysis presented in the paper is based on the method of integral manifolds, and it allowed us to present the droplet evaporation rate as the sum of the evaporation rate predicted by the model based on the assumption that [Formula: see text] and the correction proportional to ε. The correction is shown to be particularly important in the case of small water and methanol droplets (diameters less than 5 μm) evaporating in air at low pressure (0.1 atm.). In this case, this correction could reach 35% of the original evaporation rate. In the case of evaporation of relatively large droplets (with radii more than 10 μm) in air at atmospheric and higher pressures, these corrections are shown to be small (less than [Formula: see text] of the evaporation rate predicted by the model based on the assumption that [Formula: see text]).

In our previous work, we built the model of PPARγ dependent pathways involved in the development of the psoriatic lesions. Peroxisome proliferator-activated receptor gamma (PPARγ) is a nuclear receptor and transcription factor which regulates the expression of many proinflammatory genes. We tested the hypothesis that low levels of PPARγ expression promote the development of psoriatic lesions triggering the IL17-related signaling cascade. Skin samples of normally looking and lesional skin donated by psoriasis patients and psoriatic CD3+ Tcells samples (n = 23) and samples of healthy CD3+ T cells donated by volunteers (n = 10) were analyzed by real-time PCR, ELISA and immunohistochemistry analysis. We found that the expression of PPARγ is downregulated in human psoriatic skin and laser treatment restores the expression. The expression of IL17, STAT3, FOXP3, and RORC in psoriatic skin before and after laser treatment were correlated with PPARγ expression according to the reconstructed model of PPARγ pathway in psoriasis.In conclusion, we report that PPARγ weakens the expression of genes that contribute in the development of psoriatic lesion. Our data show that transcriptional regulation of PPARγ expression by FOSL1 and by STAT3/FOSL1 feedback loop may be central in the psoriatic skin and T-cells.

In our previous work, we built the model of PPARγ dependent pathways involved in the development of the psoriatic lesions. Peroxisome proliferator-activated receptor gamma (PPARγ) is a nuclear receptor and transcription factor which regulates the expression of many proinflammatory genes. We tested the hypothesis that low levels of PPARγ expression promote the development of psoriatic lesions triggering the IL17-related signaling cascade. Skin samples of normally looking and lesional skin donated by psoriasis patients and psoriatic CD3+ Tcells samples (n = 23) and samples of healthy CD3+ T cells donated by volunteers (n = 10) were analyzed by real-time PCR, ELISA and immunohistochemistry analysis. We found that the expression of PPARγ is downregulated in human psoriatic skin and laser treatment restores the expression. The expression of IL17, STAT3, FOXP3, and RORC in psoriatic skin before and after laser treatment were correlated with PPARγ expression according to the reconstructed model of PPARγ pathway in psoriasis.In conclusion, we report that PPARγ weakens the expression of genes that contribute in the development of psoriatic lesion. Our data show that transcriptional regulation of PPARγ expression by FOSL1 and by STAT3/FOSL1 feedback loop may be central in the psoriatic skin and T-cells.

Psoriasis is a multigene and multifactorial skin disease with heterogeneous genetic inheritance. Mental disorders participate in the development of psoriasis as predisposing factors; a correlation of dermatological diseases with pathological anxiety and stress was shown. Meanwhile, there are no studies describing molecular mechanisms of the linkages between psycho-emotional disorders and skin diseases. The aim of this study is to find the associations between SNP in genes COMT (rs4680), DBH (rs141116007), CCKAR (rs1800857) and CCKBR (rs1805002), and psoriasis. Patients were selected according to the 10th revision of International Classification of Diseases (L-40). The sample size was 88 patients. The size of the control sample (population control) was 365 people. Genotyping was performed using PCR-RFLP and real-time PCR. Statistical analysis was performed using WinPepi software. Identification of complex genotypes was performed by the Monte Carlo method using APSampler 3.6.1 algorithm. Among the studied genes, only GA genotype of COMT gene is significantly associated with psoriasis [χ2 = 19.163 (p = 1.3E−5), F (p) = 1.2E−5, OR 3.47 (CI 99% = 1.61–7.91)]. At the moment, the functional significance of this phenomenon is difficult to explain.

A wide range of dynamic models, including those of heating, evaporation and ignition processes in fuel sprays, is characterised by large differences in the rates of change of variables. Invariant manifold theory is an effective technique for investigation of these systems. In constructing the asymptotic expansions of slow invariant manifolds, it is commonly assumed that a limiting algebraic equation allows one to find a slow surface explicitly. This is not always possible due to the fact that the degenerate equation for this surface (small parameter equal to zero) is either a high degree polynomial or transcendental. In many problems, however, the slow surface can be described in a parametric form. In this case, the slow invariant manifold can be found in parametric form using asymptotic expansions. If this is not possible, it is necessary to use an implicit presentation of the slow surface and obtain asymptotic representations for the slow invariant manifold in an implicit form. The results of development of the mathematical theory of these approaches and the applications of this theory to some examples related to modelling combustion processes, including those in sprays, are presented.

The perturbed mK(3,1) equation is restudied to further explore the dynamics of solitary wave solutions by combining the geometric singular perturbation theorem and bifurcation analysis in this paper. Besides the solitary waves presented in literature, we show that this equation possesses a family of solitary waves which decay to some constants determined by their wave speeds and a parameter. It is shown that a portion of the solitary wave solutions to the mK(3,1) equation will persist under small perturbations and the wave speed selection principle is presented as well. In addition to the solitary waves, each of which has only one peak or valley and approximates to a solitary wave of the unperturbed equation as the perturbation parameter tends to zero, we theoretically prove the existence of a new type of solitary waves with the coexisting peak and valley. The numerical simulations are carried out, and the results are in complete agreement with our theoretical analysis.

Since the pathogenesis of atopic dermatitis could not be explained only by a population genetic and phenotypic profiles, epigenetic regulator factors have been considered. Epigenetics is the study of inherited changes in gene expression that are not related to changes in its nucleotide sequence. One of the main classical regulatory mechanisms in human cells is DNA methylation. It is not clear how permanent modifications caused by this process are and whether it is possible to affect them by changing the activity of enzymes that trigger remodeling reactions. In this chapter we analyze all recent studies in this field. We focus more on methylation of innate and adaptive immune factors, with an emphasis on T-lymphocyte genes such as CD3, CD4, and CD8.

BackgroundPlaque psoriasis is a chronic autoimmune disorder characterized by the development of red scaly plaques. To date psoriasis lesional skin transcriptome has been extensively studied, whereas only few proteomic studies of psoriatic skin are available.AimThe aim of this study was to compare protein expression patterns of lesional and normally looking skin of psoriasis patients with skin of the healthy volunteers, reveal differentially expressed proteins and identify changes in cell metabolism caused by the disease.MethodsSkin samples of normally looking and lesional skin donated by psoriasis patients (n = 5) and samples of healthy skin donated by volunteers (n = 5) were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). After protein identification and data processing, the set of differentially expressed proteins was subjected to protein ontology analysis to characterize changes in biological processes, cell components and molecular functions in the patients’ skin compared to skin of the healthy volunteers.ResultsThe performed analysis identified 405 and 59 differentially expressed proteins in lesional and normally looking psoriatic skin compared to healthy control. We discovered decreased expression of KNG1, APOE, HRG, THBS1 and PLG in normally looking skin of the patients. Presumably, these changes were needed to protect the epidermis from spontaneous activation of kallikrein-kinin system and delay the following development of inflammatory response. In lesional skin, we identified several large groups of proteins with coordinated expression. Mainly, these proteins were involved in different aspects of protein and RNA metabolism, namely ATP synthesis and consumption; intracellular trafficking of membrane-bound vesicles, pre-RNA processing, translation, chaperoning and degradation in proteasomes/immunoproteasomes.ConclusionOur findings explain the molecular basis of metabolic changes caused by disease in skin lesions, such as faster cell turnover and higher metabolic rate. They also indicate on downregulation of kallikrein-kinin system in normally looking skin of the patients that would be needed to delay exacerbation of the disease. Data are available via ProteomeXchange with identifier PXD021673.

Interactions of genes in intersecting signaling pathways, as well as environmental influences, are required for the development of psoriasis. Peroxisome proliferator-activated receptor gamma (PPARγ) is a nuclear receptor and transcription factor which inhibits the expression of many proinflammatory genes. We tested the hypothesis that low levels of PPARγ expression promote the development of psoriatic lesions. We combined experimental results and network functional analysis to reconstruct the model of PPARγ-downregulated signaling in psoriasis. We hypothesize that the expression of IL17, STAT3, FOXP3, and RORC and FOSL1 genes in psoriatic skin is correlated with the level of PPARγ expression, and they belong to the same signaling pathway that regulates the development of psoriasis lesion.

Interactions of genes in intersecting signaling pathways, as well as environmental influences, are required for the development of psoriasis. Peroxisome proliferator-activated receptor gamma (PPARγ) is a nuclear receptor and transcription factor which inhibits the expression of many proinflammatory genes. We tested the hypothesis that low levels of PPARγ expression promote the development of psoriatic lesions. We combined experimental results and network functional analysis to reconstruct the model of PPARγ downregulated signaling in psoriasis. We hypothesize that the expression of IL17, STAT3, FOXP3, and RORC and FOSL1 genes in psoriatic skin are correlated with the level of PPARγ expression and they belong to the same signaling pathway that regulates the development of psoriasis lesion.

The PD-regulators design problem for the singularly perturbed control system is considered in the paper. It is shown that this problem can be reduced to the P-regulators design problems for two subsystems of the lower dimension.

The studies of the phenomena of transient traveling waves on transmission lines are interesting in the theoretical phase simulations and real applications. The traveling waves problem for the singularly perturbed semi-linear parabolic equations is considered in the paper. It is shown that the corresponding problem for a singularly perturbed ODE system can be reduced to a certain problem of lower dimension using a splitting transformation based on the technique of slow and fast integral manifolds.

Our modern lifestyle and low air quality provoke disorders of the respiratory system, which are often chronic. This chapter focuses on two major chronic respiratory illnesses: asthma and chronic obstructive pulmonary disease (COPD). Hyperstimulation of the immune response leads to asthma progression, while the inflammation-mediated destruction of the pulmonary tissues is a critical element in the development of COPD.

In children with normal hearing, inflammatory disorders caused by infections of the middle ear (otitis media) are the most common ear illnesses. Many of older adults experience some level of hearing loss. Several factors can lead to either a partial loss or the total inability to hear (deafness) including exposure to noise, a hereditary predisposition, chronic infections, traumas, medications, and aging.