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Copyright © 2021 The Korean Academy of Asthma, Allergy and Clinical Immunology. Arginine kinase (AK) was first identified as an allergen in the Indian-meal moth and subsequently shown to occur as allergen in various invertebrates and shellfish. The cDNA coding for AK from the house dust mite (HDM) species Dermatophagoides pteronyssinus, Der p 20, has been isolated, but no recombinant Der p 20 (rDer p 20) allergen has been produced and characterized so far. We report the expression of Der p 20 as recombinant protein in Escherichia coli. rDer p 20 was purified and shown to be a monomeric, folded protein by size exclusion chromatography and circular dichroism spectroscopy, respectively. Using AK-specific antibodies, Der p 20 was found to occur mainly in HDM bodies, but not in fecal particles. Thirty percent of clinically well-characterized HDM allergic patients (n = 98) whose immunoglobulin E (IgE) reactivity profiles had been determined with an extensive panel of purified HDM allergens (Der f 1, 2; Der p 1, 2, 4, 5, 7, 10, 11, 14, 15, 18, 21, 23 and 37) showed IgE reactivity to Der p 20. IgE reactivity to Der p 20 was more frequently associated with lung symptoms. AKs were detected in several invertebrates with specific antibodies and Der p 20 showed IgE cross-reactivity with AK from shrimp (Litopenaeus vannamei). Thus, Der p 20 is a cross-reactive HDM allergen and may serve as a diagnostic marker for HDM-induced lung symptoms such as asthma.

Copyright © 2021 The Korean Academy of Asthma, Allergy and Clinical Immunology. Arginine kinase (AK) was first identified as an allergen in the Indian-meal moth and subsequently shown to occur as allergen in various invertebrates and shellfish. The cDNA coding for AK from the house dust mite (HDM) species Dermatophagoides pteronyssinus, Der p 20, has been isolated, but no recombinant Der p 20 (rDer p 20) allergen has been produced and characterized so far. We report the expression of Der p 20 as recombinant protein in Escherichia coli. rDer p 20 was purified and shown to be a monomeric, folded protein by size exclusion chromatography and circular dichroism spectroscopy, respectively. Using AK-specific antibodies, Der p 20 was found to occur mainly in HDM bodies, but not in fecal particles. Thirty percent of clinically well-characterized HDM allergic patients (n = 98) whose immunoglobulin E (IgE) reactivity profiles had been determined with an extensive panel of purified HDM allergens (Der f 1, 2; Der p 1, 2, 4, 5, 7, 10, 11, 14, 15, 18, 21, 23 and 37) showed IgE reactivity to Der p 20. IgE reactivity to Der p 20 was more frequently associated with lung symptoms. AKs were detected in several invertebrates with specific antibodies and Der p 20 showed IgE cross-reactivity with AK from shrimp (Litopenaeus vannamei). Thus, Der p 20 is a cross-reactive HDM allergen and may serve as a diagnostic marker for HDM-induced lung symptoms such as asthma.

© 2020 Elsevier B.V. The chemical and biochemical analysis of bodily fluids after death is an important thanatochemical approach to assess the cause and time since death. Vitreous humor (VH) has been used as a biofluid for forensic purposes since the 1960s. Due to its established relevance in toxicology, a literature review highlighting the use of VH with an emphasis on endogenous compounds has not yet been undertaken. VH is a chemically complex aqueous solution of carbohydrates, proteins, electrolytes and other small molecules present in living organisms; this biofluid is useful tool for its isolated environment, preserved from bacterial contamination, decomposition, autolysis, and metabolic reactions. The post-mortem analysis of VH provides an important tool for the estimation of the post-mortem interval (PMI), which can be helpful in determining the cause of death. Consequently, the present review evaluates the recent chemical and biochemical advances with particular importance on the endogenous compounds present at the time of death and their modification over time, which are valuable for the PMI prediction and to identify the cause of death.

© 2020 Elsevier B.V. The chemical and biochemical analysis of bodily fluids after death is an important thanatochemical approach to assess the cause and time since death. Vitreous humor (VH) has been used as a biofluid for forensic purposes since the 1960s. Due to its established relevance in toxicology, a literature review highlighting the use of VH with an emphasis on endogenous compounds has not yet been undertaken. VH is a chemically complex aqueous solution of carbohydrates, proteins, electrolytes and other small molecules present in living organisms; this biofluid is useful tool for its isolated environment, preserved from bacterial contamination, decomposition, autolysis, and metabolic reactions. The post-mortem analysis of VH provides an important tool for the estimation of the post-mortem interval (PMI), which can be helpful in determining the cause of death. Consequently, the present review evaluates the recent chemical and biochemical advances with particular importance on the endogenous compounds present at the time of death and their modification over time, which are valuable for the PMI prediction and to identify the cause of death.

© 2020 The Authors Background: Haemostatic activation and hypercoagulability are frequently observed in patients with metastatic colorectal cancer (mCRC), increase risk of venous thromboembolism (VTE) and have been implicated in tumour proliferation and progression. To date, the association of haemostatic biomarkers with oncologic outcomes including overall survival (OS), progression free survival (PFS) and disease control rate (DCR) is incompletely understood. Methods: Within the framework of the Vienna Cancer and Thrombosis Study, a prospective observational cohort study, we conducted an exploratory analysis to investigate the association of six known biomarkers of haemostasis with oncologic outcomes in 99 patients with mCRC prior to chemotherapy initiation. Results: Patients with high levels of factor VIII activity (FVIII), D-dimer, prothrombin fragment 1 + 2 (F1 + 2) and fibrinogen (defined as levels >75th percentile) had significantly shorter median OS than patients with lower levels. Elevation of four biomarkers was associated with mortality in multivariable analysis, adjusting for age, sex, number of metastatic sites and VTE (hazard ratio [95% CI] for death per doubling of levels: FVIII: 2.06 [1.28–3.30]; sP-selectin: 1.55 [1.07–2.24]; D-dimer: 1.40 [1.18–1.65]; F1 + 2: 1.64 [1.10–2.46]). Patients with elevated levels had numerically shorter median PFS across all markers and disease control rate (DCR) was significantly smaller in those with high levels of FVIII and F1 + 2 (adjusted odds ratio [95% CI] for DCR per doubling of levels: 0.23 [0.09–0.62] and 0.36 [0.16–0.82]) compared to patients with lower levels. Conclusion: Specific elevated haemostatic biomarkers are associated with higher mortality and partially with worse response to chemotherapy in patients with mCRC.

© 2019 Elsevier B.V. Fabry disease (FD [MIM:301500]) is an X-linked lysosomal storage disorder caused by mutations in the GLA gene. Deficient activity of its product, lysosomal enzyme α-galactosidase A (α-Gal A), leads to excessive accumulation of glycosphingolipids in cells of multiple organs. The establishing of the diagnosis is challenge in female patients because of milder clinical manifestation and normal α-Gal A activity. The globotriaosylsphingosine (lysoGb3) is described as a more sensitive diagnostic biomarker for females with pathogenic mutation in the GLA gene. Thus, the aim of this study is to improve the biochemical diagnostic efficiency for FD in females. Here we report the α-Gal A/lysoGb3 ratio as the novel biochemical criteria for diagnosis of female patients with FD, using dried blood spots (DBS) as test samples. It showed 100% sensitivity in distinguishing our group of 35 female patients from control (n = 140). Whereas measurement of α-Gal A and lysoGb3 alone showed 8.6% and 74.4% respectively. A new approach of using the ratio of α-Gal A activity to lysoGb3 concentration in DBS may provide a more accurate screening tool for identification of FD females.

© 2019 Elsevier B.V. Fabry disease (FD [MIM:301500]) is an X-linked lysosomal storage disorder caused by mutations in the GLA gene. Deficient activity of its product, lysosomal enzyme α-galactosidase A (α-Gal A), leads to excessive accumulation of glycosphingolipids in cells of multiple organs. The establishing of the diagnosis is challenge in female patients because of milder clinical manifestation and normal α-Gal A activity. The globotriaosylsphingosine (lysoGb3) is described as a more sensitive diagnostic biomarker for females with pathogenic mutation in the GLA gene. Thus, the aim of this study is to improve the biochemical diagnostic efficiency for FD in females. Here we report the α-Gal A/lysoGb3 ratio as the novel biochemical criteria for diagnosis of female patients with FD, using dried blood spots (DBS) as test samples. It showed 100% sensitivity in distinguishing our group of 35 female patients from control (n = 140). Whereas measurement of α-Gal A and lysoGb3 alone showed 8.6% and 74.4% respectively. A new approach of using the ratio of α-Gal A activity to lysoGb3 concentration in DBS may provide a more accurate screening tool for identification of FD females.

© 2019 Elsevier B.V. Fabry disease (FD [MIM:301500]) is an X-linked lysosomal storage disorder caused by mutations in the GLA gene. Deficient activity of its product, lysosomal enzyme α-galactosidase A (α-Gal A), leads to excessive accumulation of glycosphingolipids in cells of multiple organs. The establishing of the diagnosis is challenge in female patients because of milder clinical manifestation and normal α-Gal A activity. The globotriaosylsphingosine (lysoGb3) is described as a more sensitive diagnostic biomarker for females with pathogenic mutation in the GLA gene. Thus, the aim of this study is to improve the biochemical diagnostic efficiency for FD in females. Here we report the α-Gal A/lysoGb3 ratio as the novel biochemical criteria for diagnosis of female patients with FD, using dried blood spots (DBS) as test samples. It showed 100% sensitivity in distinguishing our group of 35 female patients from control (n = 140). Whereas measurement of α-Gal A and lysoGb3 alone showed 8.6% and 74.4% respectively. A new approach of using the ratio of α-Gal A activity to lysoGb3 concentration in DBS may provide a more accurate screening tool for identification of FD females.

© 2019 Elsevier B.V. Fabry disease (FD [MIM:301500]) is an X-linked lysosomal storage disorder caused by mutations in the GLA gene. Deficient activity of its product, lysosomal enzyme α-galactosidase A (α-Gal A), leads to excessive accumulation of glycosphingolipids in cells of multiple organs. The establishing of the diagnosis is challenge in female patients because of milder clinical manifestation and normal α-Gal A activity. The globotriaosylsphingosine (lysoGb3) is described as a more sensitive diagnostic biomarker for females with pathogenic mutation in the GLA gene. Thus, the aim of this study is to improve the biochemical diagnostic efficiency for FD in females. Here we report the α-Gal A/lysoGb3 ratio as the novel biochemical criteria for diagnosis of female patients with FD, using dried blood spots (DBS) as test samples. It showed 100% sensitivity in distinguishing our group of 35 female patients from control (n = 140). Whereas measurement of α-Gal A and lysoGb3 alone showed 8.6% and 74.4% respectively. A new approach of using the ratio of α-Gal A activity to lysoGb3 concentration in DBS may provide a more accurate screening tool for identification of FD females.

© 2019 Elsevier B.V. Fabry disease (FD [MIM:301500]) is an X-linked lysosomal storage disorder caused by mutations in the GLA gene. Deficient activity of its product, lysosomal enzyme α-galactosidase A (α-Gal A), leads to excessive accumulation of glycosphingolipids in cells of multiple organs. The establishing of the diagnosis is challenge in female patients because of milder clinical manifestation and normal α-Gal A activity. The globotriaosylsphingosine (lysoGb3) is described as a more sensitive diagnostic biomarker for females with pathogenic mutation in the GLA gene. Thus, the aim of this study is to improve the biochemical diagnostic efficiency for FD in females. Here we report the α-Gal A/lysoGb3 ratio as the novel biochemical criteria for diagnosis of female patients with FD, using dried blood spots (DBS) as test samples. It showed 100% sensitivity in distinguishing our group of 35 female patients from control (n = 140). Whereas measurement of α-Gal A and lysoGb3 alone showed 8.6% and 74.4% respectively. A new approach of using the ratio of α-Gal A activity to lysoGb3 concentration in DBS may provide a more accurate screening tool for identification of FD females.

© 2019 Elsevier B.V. Fabry disease (FD [MIM:301500]) is an X-linked lysosomal storage disorder caused by mutations in the GLA gene. Deficient activity of its product, lysosomal enzyme α-galactosidase A (α-Gal A), leads to excessive accumulation of glycosphingolipids in cells of multiple organs. The establishing of the diagnosis is challenge in female patients because of milder clinical manifestation and normal α-Gal A activity. The globotriaosylsphingosine (lysoGb3) is described as a more sensitive diagnostic biomarker for females with pathogenic mutation in the GLA gene. Thus, the aim of this study is to improve the biochemical diagnostic efficiency for FD in females. Here we report the α-Gal A/lysoGb3 ratio as the novel biochemical criteria for diagnosis of female patients with FD, using dried blood spots (DBS) as test samples. It showed 100% sensitivity in distinguishing our group of 35 female patients from control (n = 140). Whereas measurement of α-Gal A and lysoGb3 alone showed 8.6% and 74.4% respectively. A new approach of using the ratio of α-Gal A activity to lysoGb3 concentration in DBS may provide a more accurate screening tool for identification of FD females.

© 2019 Elsevier B.V. Fabry disease (FD [MIM:301500]) is an X-linked lysosomal storage disorder caused by mutations in the GLA gene. Deficient activity of its product, lysosomal enzyme α-galactosidase A (α-Gal A), leads to excessive accumulation of glycosphingolipids in cells of multiple organs. The establishing of the diagnosis is challenge in female patients because of milder clinical manifestation and normal α-Gal A activity. The globotriaosylsphingosine (lysoGb3) is described as a more sensitive diagnostic biomarker for females with pathogenic mutation in the GLA gene. Thus, the aim of this study is to improve the biochemical diagnostic efficiency for FD in females. Here we report the α-Gal A/lysoGb3 ratio as the novel biochemical criteria for diagnosis of female patients with FD, using dried blood spots (DBS) as test samples. It showed 100% sensitivity in distinguishing our group of 35 female patients from control (n = 140). Whereas measurement of α-Gal A and lysoGb3 alone showed 8.6% and 74.4% respectively. A new approach of using the ratio of α-Gal A activity to lysoGb3 concentration in DBS may provide a more accurate screening tool for identification of FD females.

© Springer Science+Business Media, LLC, part of Springer Nature 2020. We describe here the Oncobox method for scoring efficiencies of anticancer target drugs (ATDs) using high throughput gene expression data. The method rationale, design, and validation are given along with the examples of its practical applications in biomedicine. The method is based on the analysis of intracellular molecular pathways activation and measuring expressions of molecular target genes for every ATD under consideration. Using Oncobox method requires collection of normal (control) expression profiles and annotated databases of molecular pathways and drug target genes. Both microarray and RNA sequencing profiles are acceptable, although the latter type of data prevails in the most recent applications of this technique.

© Springer Science+Business Media, LLC, part of Springer Nature 2020. Intracellular molecular pathways (IMPs) control all major events in the living cell. IMPs are considered hotspots in biomedical sciences and thousands of IMPs have been discovered for humans and model organisms. Knowledge of IMPs activation is essential for understanding biological functions and differences between the biological objects at the molecular level. Here we describe the Oncobox system for accurate quantitative scoring activities of up to several thousand molecular pathways based on high throughput molecular data. Although initially designed for gene expression and mainly RNA sequencing data, Oncobox is now also applicable for quantitative proteomics, microRNA and transcription factor binding sites mapping data. The Oncobox system includes modules of gene expression data harmonization, aggregation and comparison and a recursive algorithm for automatic annotation of molecular pathways. The universal rationale of Oncobox enables scoring of signaling, metabolic, cytoskeleton, immunity, DNA repair, and other pathways in a multitude of biological objects. The Oncobox system can be helpful to all those working in the fields of genetics, biochemistry, interactomics, and big data analytics in molecular biomedicine.

© Springer Science+Business Media, LLC, part of Springer Nature 2020. DNA mutations govern cancer development. Cancer mutation profiles vary dramatically among the individuals. In some cases, they may serve as the predictors of disease progression and response to therapies. However, the biomarker potential of cancer mutations can be dramatically (several orders of magnitude) enhanced by applying molecular pathway-based approach. We developed Oncobox system for calculation of pathway instability (PI) values for the molecular pathways that are aggregated mutation frequencies of the pathway members normalized on gene lengths and on number of genes in the pathway. PI scores can be effective biomarkers in different types of comparisons, for example, as the cancer type biomarkers and as the predictors of tumor response to target therapies. The latter option is implemented using mutation drug score (MDS) values, which algorithmically rank the drugs capacity of interfering with the mutated molecular pathways. Here, describe the mathematical basis and algorithms for PI and MDS values calculation, validation and implementation. The example analysis is provided encompassing 5956 human tumor mutation profiles of 15 cancer types from The Cancer Genome Atlas (TCGA) project, that totally make 2,316,670 mutations in 19,872 genes and 1748 molecular pathways, thus enabling ranking of 128 clinically approved target drugs. Our results evidence that the Oncobox PI and MDS approaches are highly useful for basic and applied aspects of molecular oncology and pharmacology research.

© 2019, © 2019 Informa UK Limited, trading as Taylor  &  Francis Group. Introduction: Due to the polymorphic clinical presentations and manifestations of systemic lupus erythematosus (SLE), biomarkers with enough diagnostic and prognostic value are of paramount importance. Recently, anti-double stranded DNA (anti-dsDNA) auto-antibodies have been proposed to monitor the response to different therapies. It has also been suggested that they should be employed as entry markers in trial studies. However, their clinical use remains still debated and, sometimes, controversial, due to conflicting findings reported. Areas covered: Through an extensive literature review, we evaluated changes in anti-dsDNA auto-antibodies levels before and after the administration of the treatment (either biological or non-biological). Expert opinion: Anti-dsDNA auto-antibodies related findings are still difficult to compare mainly because of the different detecting methods employed, even though in most studies included in this review a consistent decreasing pattern after the treatment seems to emerge. Hence, if properly standardized, anti-dsDNA auto-antibody profile may be a reliable biomarker to monitor the effectiveness of biologics as well as of non-biological drugs, especially if grouped in composite outcomes scores, such as the ‘Lupus Multivariable Outcome Score’ (LUMOS) or measured with other biomarkers, such as anti-nucleosome auto-antibodies. We recommend the assessment of anti-dsDNA auto-antibodies levels in both daily practice and research settings.

This study aimed to investigate the effects of propofol through evaluating its interaction with nitric oxide (NO), hydrogen sulfide (H2S), and carbon monoxide (CO). Wistar male rats were divided in 4 groups: (1) bolus injection of propofol (1% 10 mg/mL, 100 mg/kg bw, i.p.); (2) Nω-nitro-l-arginine methyl ester (L-NAME; NO synthase inhibitor, 60 mg/kg bw, i.p.) + bolus injection of propofol (1% 10 mg/mL, 100 mg/kg bw, i.p.); (3) DL-propargylglycine (DL-PAG; H2S synthase inhibitor, 50 mg/kg bw, i.p.) + bolus injection of propofol (1% 10 mg/mL, 100 mg/kg bw, i.p.); (4) zinc protoporphyrin IX (ZnPPIX; CO synthase inhibitor, 50 μmol/kg bw, i.p.) + bolus injection of propofol (1% 10 mg/mL, 100 mg/kg bw, i.p.). Increased levels of albumins, low-density lipoproteins, alkaline phosphatase, amylase, high-sensitivity Troponin T, and fibrinogen were found in L-NAME + propofol group. Platelet crit, platelet count, total cholesterol, and high-density lipoproteins were elevated in ZnPPIX + propofol group. Hydrogen peroxide was increased in all groups treated with gasotransmitters inhibitors. Reduced glutathione was reduced in all groups, superoxide dismutase activity only in L-NAME + propofol. The effect of propofol on various biochemical, haematological, and oxidative stress markers may be at least in part mediated through interaction with 3 estimated gasotransmitters.

© 2019 The Authors Background: The aim was to estimate the prevalence of harmful alcohol use in relation to socio-demographic characteristics among acutely ill medical patients, and examine identification measures of alcohol use, including the alcohol biomarker phosphatidylethanol 16:0/18:1 (PEth). Methods: A cross-sectional study, lasting one year at one hospital in Oslo, Norway and one in Moscow, Russia recruiting acute medically ill patients (≥ 18 years), able to give informed consent. Self-reported data on socio-demographics, mental distress (Symptom Check List-5), alcohol use (Alcohol Use Disorder Identification Test-4 (AUDIT-4) and alcohol consumption past 24 h were collected. PEth and alcohol concentration were measured in whole blood. Results: Of 5883 participating patients, 19.2% in Moscow and 21.1% in Oslo were harmful alcohol users, measured by AUDIT-4, while the prevalence of PEth-positive patients was lower: 11.4% in Oslo, 14.3% in Moscow. Men in Moscow were more likely to be harmful users by AUDIT-4 and PEth compared to men in Oslo, except of those being ≥ 71 years. Women in Oslo were more likely to be harmful users compared to those in Moscow by AUDIT-4, but not by PEth for those aged < 61 years. Conclusions: The prevalence of harmful alcohol use was high at both study sites. The prevalence of harmful alcohol use was lower when assessed by PEth compared to AUDIT-4. Thus, self-reporting was the most sensitive measure in revealing harmful alcohol use among all groups except for women in Moscow. Hence, screening and identification with objective biomarkers and self-reporting might be a method for early intervention.

© 2019 by the authors. Licensee MDPI, Basel, Switzerland. Adiponectin is encoded by the ADIPOQ gene and participates in the pathogenesis of cardiovascular and metabolic diseases. The goal of the study was to assess associations of rs17300539, rs266729, rs182052, rs2241766, and rs17366743 single nucleotide polymorphisms (SNPs) of the ADIPOQ gene with concentrations of serum adiponectin and with coronary atherosclerosis and type 2 diabetes mellitus in 447 patients (316 men and 131 women) subjected to coronary angiography. SNPs of the ADIPOQ gene of the study participants were genotyped using real-time PCR. Multivariate linear regression adjusted for covariates revealed significant association between rs182052 SNP and serum adiponectin concentration (β= –0.11; 95% confidence interval (95%CI): – 0.19, –0.03; p = 0.016). Regression analysis revealed an increase in prevalence of unstable angina (OR (odds ratio) = 2.55; 95%CI 1.4–4.82; p = 0.018) and coronary artery disease (OR = 1.55; 95%CI 1.15– 2.09; p = 0.021) per copy of the rs182052 A allele. Prevalence of type 2 diabetes mellitus was higher in subjects with the rs182052 A allele (OR = 2.29; 95%CI 1.29-4.21; p = 0.024). Regression analysis of rs266729 showed that prevalence of unstable angina was increased (OR = 3.59; 95%CI 1.17–10.01; p = 0.045) in the subjects with the GG genotype and prevalence of coronary artery disease (CAD) was significantly increased (OR = 1.48; 95%CI 1.09–2.03; p = 0.045) per copy of the G allele. Haplotype analysis revealed that the subjects with the GCATT haplotype have lower adiponectin levels (β= – 0.15; p = 0.042) and higher prevalence of unstable angina (OR = 3.597; p = 0.007) compared with reference haplotype carriers. Thus, the results indicate that minor A allele of rs182052 of the ADIPOQ gene is significantly associated with a decrease in serum adiponectin levels, and two SNPs (rs182052 and rs266729) of the ADIPOQ gene are significantly associated with cardiovascular and metabolic diseases.

© 2019 Elsevier Inc. In order to investigate the prevalence and prognostic value of the polymorphic variant (1245A>C) of the HSD3B1 gene, in the tumors of patients with castration-resistant prostate cancer, we retrospectively analyzed a small number of tumor samples from 44 patients by genomic sequencing. We noticed a relatively high prevalence in the overall study group (n = 23; 52.2%) as well as in the subgroup of patients undergoing second systemic treatment (n = 20; 51.2%) where we assessed for survival outcomes. However, this alteration was neither associated with the time to progression nor with survival.