Effect of PUVA and NB-UVB Therapy on the Skin Cytokine Profile in Patients with Mycosis Fungoides.

BACKGROUND: Mycosis fungoides (MF) is the most common subtype of cutaneous T-cell lymphoma. The aim of the present study was to produce up-to-date information on different phototherapy approaches on skin cytokines in patients with MF. METHODS: A total of 27 patients with mycosis fungoides were treated with phototherapy: NB-UVB (narrow-band ultraviolet B therapy) (10 patients) and PUVA (long-wavelength ultraviolet radiation of spectrum A with the use of skin-photosensitizing furocoumarins) therapy (17 patients). Evaluation of the effectiveness of treatment was carried out using BSA (body surface area) and the modified assessment of the severity of the skin lesions scale (mSWAT) used to quantify tumor mass in cutaneous T-cell lymphomas. Average numbers of procedures were 30.2 and 27.8 in the NB-UVB and PUVA groups, respectively. The median total dose of NB-UVB irradiation was 19.9 J/cm2 and PUVA therapy was 104.0 J/cm2. The overall response to therapy including complete and partial remission was 74.9% in the total group; 70% in the NB-UVB group, and 77.7% in the PUVA therapy group. In the obtained biopsies from lesions, surrounding tissue before treatment and skin samples of four healthy volunteers, the concentration of the IL-1ß, IL-4, IL-6, IL-10, IL-17A, IL-17F, IL-21, IL-22, IL-23, IL-25, IL-31, IL-33, IFN-γ, sCD40L, and TNF-α cytokines was studied. An increase in IL-4 and TNF-α levels was shown in the lesional skin of patients compared to the skin of healthy controls. After the treatment, positive correlations of mSWAT with the levels of IL22, IL33, and TNF-α in the tumor tissue were found. The levels of IL10 and IFN-γ after PUVA treatment were increased in comparison to baseline. There was no difference in cytokine levels before/after NB-UVB therapy.

A Cross-sectional Study of Plasma Trace Elements and Vitamins Content in Androgenetic Alopecia in Men.

Androgenetic alopecia (AGA) is the most common variant of male pattern baldness in which occurrence and development of multiple genetic, hormonal, and metabolic factors are involved. We aimed to estimate plasma element content (Mg, Ca, Zn, Cu, Se, Fe), vitamin status (B12, D, E, and folic acid) in patients with AGA using direct colorimetric tests or atomic absorption spectrometry, and the influence of these parameters in the formation of various hair loss patterns. The study included 50 patients with I-IV stages of AGA divided into two groups with normal and high levels of dihydrotestosterone compared with 25 healthy individuals. The presence of two patterns of pathological hair loss in the androgen-dependent (parietal) and androgen-independent (occipital) areas of the scalp was confirmed. It was shown that all patients with AGA have a deficiency of elements (Zn, Cu, Mg, Se) and vitamins (B12, E, D, folic acid). However, the hair loss rate was not due to their content. А positive interrelation between quantitative trichogram parameters in the occipital region and iron metabolism in pairs "hair density vs Fe" and "hair diameter vs ferritin" was shown. In turn, in the parietal region, an inverse correlation of hair diameter with plasma Cu level was found, the most pronouncing in patients with high levels of dihydrotestosterone. The obtained results indicate the importance of multiple micronutrient deficiencies in the AGA occurrence accompanied by the existence of two different hair loss patterns, differently related to the content of certain trace elements and androgens in the blood.

Plasma Zinc Levels in Males with Androgenetic Alopecia as Possible Predictors of the Subsequent Conservative Therapy's Effectiveness.

Androgenic alopecia (AGA) is the most common type of progressive hair loss in man. The search for reliable predictors of the conservative treatment's effectiveness is an urgent problem today. Forty-eight patients with AGA, stages I-IV by the Norwood-Hamilton scale, were treated for 4 months with 5% topical minoxidil joints with corrections for trace element and vitamin imbalances. In most cases, the positive therapy's effect was shown in the parietal but not in the occipital area, whereas that effect was observed in others. The attempts to associate the therapy's effectiveness with initially defined genetic, hormonal, and metabolic parameters showed the absence of differences between groups with positive and negative outcomes. Among the studied nutrient parameters (Zn, Cu, Mg, Ca, Fe, and Se, as well as vitamins B12, E, D, and folic acid), differences between these groups was shown in zinc content only. The starting point from a zinc plasma level above 10 µmol/L likely provides the success of the subsequent conservative therapy and correlates with an increase in the hair density and diameter in the parietal area. The integral predictive value of the Zn plasma level was assessed as 72.3% (positive predictive value: -88%; and negative predictive value: -55%).

Apremilast Pharmacogenomics in Russian Patients with Moderate-to-Severe and Severe Psoriasis.

One of the target drugs for plaque psoriasis treatment is apremilast, which is a selective phosphodiesterase 4 (PDE4) inhibitor. In this study, 34 moderate-to-severe and severe plaque psoriasis patients from Russia were treated with apremilast for 26 weeks. This allowed us to observe the effectiveness of splitting patient cohorts based on clinical outcomes, which were assessed using the Psoriasis Area Severity Index (PASI). In total, 14 patients (41%) indicated having an advanced outcome with delta PASI 75 after treatment; 20 patients indicated having moderate or no effects. Genome variability was investigated using the Illumina Infinium Global Screening Array. Genome-wide analysis revealed apremilast therapy clinical outcome associations at three compact genome regions with undefined functions situated on chromosomes 2, 4, and 5, as well as on a single single-nucleotide polymorphism (SNP) on chromosome 23. Pre-selected SNP sets were associated with psoriasis vulgaris analysis, which was used to identify four SNP-associated targeted therapy efficiencies: IL1ß (rs1143633), IL4 (IL13) (rs20541), IL23R (rs2201841), and TNFα (rs1800629) genes. Moreover, we showed that the use of the global polygenic risk score allowed for the prediction of onset psoriasis in Russians. Therefore, these results can serve as a starting point for creating a predictive model of apremilast therapy response in the targeted therapy of patients with psoriasis vulgaris.

Reconstructing genetic history of Siberian and Northeastern European populations.

Siberia and Northwestern Russia are home to over 40 culturally and linguistically diverse indigenous ethnic groups, yet genetic variation and histories of peoples from this region are largely uncharacterized. We present deep whole-genome sequencing data (∼38×) from 28 individuals belonging to 14 distinct indigenous populations from that region. We combined these data sets with additional 32 modern-day and 46 ancient human genomes to reconstruct genetic histories of several indigenous Northern Eurasian populations. We found that Siberian and East Asian populations shared 38% of their ancestry with a 45,000-yr-old Ust'-Ishim individual who was previously believed to have no modern-day descendants. Western Siberians trace 57% of their ancestry to ancient North Eurasians, represented by the 24,000-yr-old Siberian Mal'ta boy MA-1. Eastern Siberian populations formed a distinct sublineage that separated from other East Asian populations ∼10,000 yr ago. In addition, we uncovered admixtures between Siberians and Eastern European hunter-gatherers from Samara, Karelia, Hungary, and Sweden (from 8000-6600 yr ago); Yamnaya people (5300-4700 yr ago); and modern-day Northeastern Europeans. Our results provide new insights into genetic histories of Siberian and Northeastern European populations and evidence of ancient gene flow from Siberia into Europe.

Specificity of genetic diversity in D1S80 revealed by SNP-VNTR haplotyping.

BACKGROUND: The allele frequency patterns of the D1S80 variable number tandem repeat (VNTR) locus have been shown to be multimodal in many different human populations. AIM: To explore the complex allele distribution of the D1S80 polymorphic locus in different populations comparing the derived single nucleotide polymorphism (SNP) rs16824398-D1S80 haplotype frequencies in samples of European (Russians), Asian (Yakuts) and sub-Saharan African origin. SUBJECTS AND METHODS: The D1S80 locus together with its 5'-flanking region including SNP rs16824398 was amplified using allele-specific polymerase chain reaction (PCR). RESULTS: Haplotype phase determination sub-divided the total D1S80 allele spectrum into two allele sets marked by the corresponding SNP rs16824398 alleles. In non-African samples, the most frequent D1S80 alleles had 24 and 18 repeats that were associated with different SNP backgrounds (T and G alleles, respectively). Both combinations also occurred in Africans, but these samples exhibited an expanded spectrum of VNTR alleles on both SNP backgrounds. CONCLUSIONS: The sub-division of the D1S80 allele spectrum shape on the linked SNP background is indicative of populations of the main human groups. The reported differences in D1S80 allele spectra between populations of different ethnic origins can be explained by the ratios of chromosomes with T and G alleles.

Y-chromosome distribution within the geo-linguistic landscape of northwestern Russia.

Populations of northeastern Europe and the Uralic mountain range are found in close geographic proximity, but they have been subject to different demographic histories. The current study attempts to better understand the genetic paternal relationships of ethnic groups residing in these regions. We have performed high-resolution haplotyping of 236 Y-chromosomes from populations in northwestern Russia and the Uralic mountains, and compared them to relevant previously published data. Haplotype variation and age estimation analyses using 15 Y-STR loci were conducted for samples within the N1b, N1c1 and R1a1 single-nucleotide polymorphism backgrounds. Our results suggest that although most genetic relationships throughout Eurasia are dependent on geographic proximity, members of the Uralic and Slavic linguistic families and subfamilies, yield significant correlations at both levels of comparison making it difficult to denote either linguistics or geographic proximity as the basis for their genetic substrata. Expansion times for haplogroup R1a1 date approximately to 18,000 YBP, and age estimates along with Network topology of populations found at opposite poles of its range (Eastern Europe and South Asia) indicate that two separate haplotypic foci exist within this haplogroup. Data based on haplogroup N1b challenge earlier findings and suggest that the mutation may have occurred in the Uralic range rather than in Siberia and much earlier than has been proposed (12.9+/-4.1 instead of 5.2+/-2.7 kya). In addition, age and variance estimates for haplogroup N1c1 suggest that populations from the western Urals may have been genetically influenced by a dispersal from northeastern Europe (eg, eastern Slavs) rather than the converse.

Regional differences in the genetic variability of Finno-Ugric speaking Komi populations.

The Komi (Komi-Zyryan) people are one of the most numerous ethnic groups belonging to the Finno-Ugric linguistic community. They occupy an extensive territory in north Russia to the west of the Ural Mountains, in the northeast of the East European Plain. This is an area of long-term interactions between Europeans and North Asians. Genetic variability was evaluated in two geographically distinct populations, the Izhemski and Priluzski Komi. We searched for polymorphisms of the TP53 gene (a 16-bp duplication in intron 3 and three RFLPs: for Bsh1236I at codon 72, for MspI in intron 6, and for BamHI in the 3' flanking region) and for variable number tandem repeat (VNTR) polymorphisms of locus D1S80 and of the 3' untranslated region of the gene for apolipoprotein B (ApoB). Some data from our previous studies of TP53, 3'ApoB, and D1S80 variability were involved in the comparison of Komi with other Eastern European populations. Multidimensional scaling analysis of genetic distances was used for the evaluation of genetic relationships between populations. The results revealed some affinity between Priluzski Komi and Eastern Slavonic populations, and significant segregation of Izhemski Komi from other ethnic groups studied. The unique genetic features of Izhemski Komi may have been determined by their ethnogenesis or the pressure of environmental factors, such as special nutrition and adaptation to extreme climatic conditions.

Variability of the 3'APOB minisatellite locus in Eastern Slavonic populations.

OBJECTIVE: To describe and compare the 3' apolipoprotein (Apo) B minisatellite allele frequency distributions of Eastern Slavonic populations and their Uralic, Altaic, and Caucasian speaking neighbors. METHODS: Healthy individuals of 10 populations among Russians, Byelorussians, Komis and Bashkirs were studied for variable number tandem repeats (VNTRs) in the 3'ApoB minisatellite region. Data were analyzed with other results reported for this polymorphism in eastern Europeans and Siberians. RESULTS: Allele frequency spectra in Eastern Slavonic, Northern Caucasian and Finno-Ugric speaking populations are bimodal with the main peak in alleles 34-36 and a secondary mode around allele 48, whereas Altaic speaking populations have a unimodal allele frequency distribution with a peak of around 34-36 VNTRs. Population relationships were revealed using both multidimensional scaling analysis (based on Nei's genetic distance estimate) and testing for genetic heterogeneity. Eastern Slavonic populations (Russians, Ukrainians, Byelorussians) were most closely related to each other and formed a separate tight clusterwhen plotted. Testing for genetic heterogeneity among the Eastern Slavonic ethnic groups revealed maximum diversity among Byelorussians, followed by Russians, then Ukrainians. The 3'ApoB minisatellite variability reveals little heterogeneityamong the Eastern Slavonic ethnic groups, whereas there wassignificant heterogeneity for Northern Caucasian and Altaic speakers. CONCLUSION: For this 3'ApoB polymorphism the Eastern Slavonic populations, despite their wide geographical distribution, appear to be much more homogenous than other ethnic groups of the region. Multidimensional scaling analysis of these data allowed for differentiation between individual populations from an ethnic group even if there is little heterogeneity.

Apolipoprotein B 3'-VNTR polymorphism in Eastern European populations.

Apolipoprotein B 3' (3' ApoB) minisatellite polymorphism was studied in healthy unrelated individuals from the Russian Federation and the Republic of Belarus, in 10 populations from five ethnic groups: Russians, Byelorussians, Adygeis, Kalmyks and Yakuts. The analysis was carried out using PCR and electrophoresis followed by silver staining. Overall, 25 alleles of the 3' ApoB minisatellite, ranging from 25 to 55 repeats, were detected. Heterozygosity indices were high and varied from 0.73 to 0.84. The distributions of alleles of this minisatellite in the Caucasoid populations (Russians, Byelorussians and Adygeis) had a bimodal character, whereas that for Mongoloid populations (Kalmyks and Yakuts) had a unimodal distribution. Nei's genetic distances between the populations studied and some reference populations of Europe and Asia were estimated. Despite their allele distribution homogeneity, different East Slavonic ethnic groups were clearly resolved by multidimensional analyses. The East Slavonic and Adygei populations revealed a high similarity with European Caucasoids. The Mongoloid populations (Kalmyks and Yakuts) were considerably different from those of the European Caucasoid populations, but were similar to other Asian Mongoloid populations. The results demonstrate the variability of 3' ApoB minisatellite polymorphism not only in distant populations but also, to a certain extent, in genetically relative ones.