Nikonorova, Eugenia Ramilyevna

Nikonorova E., Krol T., Aksenov A., Adamov G., Baleev D.

Karamova A.E., Vorontsova A., Nikonorov A.А., Nikonorova E.R., Kubanov А.A.

Background: Despite the proven efficacy and safety of biologics in the treatment of psoriasis (Ps), a number of patients experience heterogeneity in response to therapy in both the short-term and long-term perspectives. Objective: To identify correlations between the blood cytokine levels, clinical severity indices and the effectiveness of the IL12/IL23 inhibitor (ustekinumab) therapy. Methods: The study enrolled 25 patients with psoriasis. The severity of the disease was assessed using PASI, BSA, sPGA. The clinical efficacy of ustekinumab was determined by the percentage of PASI reduction: high (≥75%) and low efficacy (≤50%). Blood cytokine levels were determined by multiplex immunological analysis (xMAP) technology. Statistical analysis was performed using RStudio and the R programming language. Results: Moderate Ps was diagnosed in 15 patients (60%), severe - in 10 (40%). The baseline levels of IL31, sCD40L and VEGF were respectively 2.3 (p=0.018), 2.3 (p=0.010), and 2 (p=0.033) times higher in severe Ps. By the 16th week, therapy was effective in 92% of patients and was accompanied by a 3.47-fold decrease in IL31 (p=0.002) and an increase in ICAM1 and VEGF by 35.8% (p=0.026) and 4.2 times (p0.001) respectively. A correlation between ∆PASI and IL12, IL17F, IL20, IL22, IL31, sCD40L, VEGF was found. Ustekinumab significantly modified cytokine interactions and neutralized their correlation with ∆PASI. Conclusion: IL31, sCD40L and VEGF baseline levels correlate with Ps severity, IL17F, IL20 and IL31 - with ∆PASI, demonstrating their potential use in objectively determining Ps severity and predicting the ustekinumab therapy effectiveness.

Kondrakhina I.N., Kondrakhin A.A., Nikonorov A., Nikonorova E.R., Deryabin D.G., Kubanov A.A.

Background: Pathological hair loss in women has emerged as a prevalent cause for seeking specialized dermatological and cosmetic services. The most common type of this condition is androgenetic alopecia, which arises due to hormonal and micronutrient imbalances.Furthermore, during the COVID-19 epidemic, there has been a notable increase in the number of female patients with pathological hair loss as a complication of the disease, with some individualsexperiencing alopecia the sole indication of asymptomatic COVID-19. Aims: The aim of the study wassearch for objective criteria for the differential diagnosis of androgenetic alopecia and post-COVID alopecia in women based on informative trichological and laboratory markers. Materials and methods: The including criteria for androgenetic alopecia (AGA) group were elevated dihydrotestosterone (DHT) levels, clinical indications of alopecia corresponding to initial stages of the condition, and a past experience of continuous observation untilFebruary 2020. For the post-COVID alopecia (COVID) group, inclusion criteria were a confirmed diagnosis of COVID-19 using RT-PCR and the presence of alopecia symptoms emerging within a year post-infection. Evaluation of quantitative characteristics of hairs was conducted was carried out based on trichogram and phototrichogram data, followed by image processing using a computer diagnostic program. Key indicators for hair growth were identified in patients' plasma, including DHT, vitamins B9 (folic acid), B12, D (25(OH)-D3 form), E, as well as calcium (Ca), iron (Fe), magnesium (Mg), selenium (Se), copper (Cu), and zinc (Zn). CART algorithm (Classification and Regression Trees) based on recursive partitioning of available data with selection of informative predictors and formation of a tree-like hierarchical structurewas applied to determine criteria to differentiate between patients with androgenetic and post-COVID alopecia. Results: Analysis of trichograms and phototrichograms revealed that unlike androgenetic alopecia, which primarily impacts hair follicles in the telogen and anagen phases in the androgen-dependent zone, post-COVID hair loss presents as a diffuse telogen effluvium pattern, involving the androgen-dependent (parietal) area of the scalp. Notably, patients with post-COVID alopecia exhibited elevated dihydrotestosterone levels compared to reference values, with no significant differencein comparison to AGA. While there were no variations in vitamin and certain trace element levels (Fe, Ca, Mg, Zn), individuals in COVID group have demonstrated a statistically significant reduction in copper content (46.4% lower than AGA; p=0.006) alongside an increase in selenium levels (24.7% higher than AGA; p=0.003). Conclusions: The performed study for the first time presents objective criteria for the differential diagnosis of androgenetic and post-COVID alopecia in women. The data obtained show a diffuse pattern of telogen effluvium after recovering from COVID-19, linked to an imbalance in trace elements - specifically, a decrease in copper (Cu) and an increase in selenium (Se). Based on this fact, the algorithm CART used allows for a highly effective differentiation of the compared variants of pathological hair loss in studied patients and forms the basis for pathogenetically justified conservative therapy.

Karamova A., Znamenskaya L., Vorontsova A., Obraztsova O., Nikonorov A., Nikonorova E., Deryabin D., Kubanov A.

Background/Objectives: Psoriasis is a chronic, inflammatory, immuno-mediated cutaneous disease characterized by a prominent TNFα-IL23/IL17 immune axis. In recent years, targeted therapies have become standard practice for managing moderate-to-severe psoriasis and have demonstrated efficacy. At the same time, identifying factors associated with the success or failure of TNFα inhibitor therapy remains one of the most difficult aspects in psoriasis treatment. Methods: A clinical, non-randomized study was conducted to evaluate the impact of TNFα inhibitors on the plasma cytokine profiles in patients with moderate-to-severe psoriasis vulgaris (ICD-10 code L40.0). The patients were treated with either etanercept, adalimumab, or infliximab for 16 weeks. Plasma cytokine profiles were assessed using a BioPlex200 System. Results: By the 16th week of therapy, a positive treatment response (PASI ≥ 75) was observed in 51 patients (63%), while 30 patients (37%) showed no response (PASI ≤ 50). When using etanercept, a positive effect was observed in 11 patients (41%), in 14 patients (52%) using adalimumab, and in 26 patients (96%) using infliximab. Analysis of the baseline cytokine levels revealed no differences between the “positive effect” and “no effect” groups, except for IL20, which was 2.61 times higher in the “positive effect” group compared to the “no effect” group, suggesting its potential predictive role in the effectiveness of therapy with TNFα inhibitors. Treatment led to a decrease in IL17F, IL31, sCD40L, and VEGF for all patients, and in IL20 for the “positive effect” group. The increase in ICAM1 in the “no effect” group suggests the possible retention of active migration and the fixation of T cells in the affected skin in these patients. No significant difference in cytokine levels was observed when categorizing patients into subgroups based on the effectiveness of therapy with etanercept, infliximab, and adalimumab; only a pre- and post-treatment difference in the whole cohort was noted. A random forest model showed the importance of VEGF, sCD40L, and ICAM1. Conclusions: The baseline levels of VEGF, sCD40L, and ICAM1, as well as IL20, could serve as potential predictors of treatment effectiveness using TNFa inhibitors. However, this hypothesis requires confirmation with a larger patient population.

Vorontsova A.A., Karamova A.E., Nikonorov A.A., Verbenko D.A., Kozlova I.V., Nikonorova E.R., Kubanov A.A.

   Introduction. The role of the cytokine environment and immune deregulation in the pathogenesis of mycosis fungoides is unquestionable. Despite the fact that one of the methods of therapy for the early stages of mycosis fungoides is phototherapy (PUVA, UVB-311 nm), the effect of ultraviolet radiation on the lymphoproliferative substrate and pathogenetic links in mycosis fungoides has not been fully studied.   Aim: to evaluate the effect of NB-UVB and PUVA therapy on the dynamics of cytokine mRNA expression in the affected skin of patients with mycosis fungoides.   Material and Methods. A comparative non-randomized study of the cytokine mRNA expression dynamics in the affected skin and of the effectiveness of phototherapy was carried out in 28 patients with early stage of mycosis fungoides. The IL4, IL17A, IL17F, and IL22 mRNA expression was determined relative to the endogenous control GAPDH using the real-time reverse transcription PCR (RT-PCR). Evaluation of the effectiveness of NB-UVB and PUVA therapy was carried out using a BSA score (skin lesion area) and a modified severity-weighted assessment tool (mSWAT) score.   Results. The study included 28 patients with early stages (IA–IIA) of mycosis fungoides; 9 patients received NB-UVB and 19 received PUVA therapy. 3.71-fold decrease in mSWAT (p < 0.008), and 3-fold decrease in BSA scores (p < 0.013) were observed in the NB-UVB-treated group. In the PUVA-treated group 3.47- and 2.19-fold lower scores of mSWAT (p < 0.001) and BSA (p < 0.001) were found. There were no significant differences in the expression of the studied cytokines in the NB-UVB-treated group; however, a significant 19 and 72 % increase in IL17F (p = 0.003) and IL22 (p = 0.021) was revealed afterPUVA therapy. Correlation analysis has shown a weak correlation between IL4 and IL17A (r = 0.43, p < 0.027), and IL17F (r = 0.43, p < 0.028) before the treatment. Under the influence of phototherapy, the formation of a cytokine network in the affected skin was observed: there were positive associations between IL4 and IL17A (r = 0.73, p < 0.001), IL17F (r = 0.7, p < 0.001) and IL22 (r = 0.43, p < 0.024); IL17A and IL17F (r = 0.78, p < 0.001); IL22 and IL17A (r = 0.63, p < 0.001) and IL17F (r = 0.66, p < 0.001). In the PUVA-treated group a high negative correlation between IL17A and mSWAT (r = -0.79415, p =0.010586), BSA (r = -0.75432, p = 0.018849) were found.   Conclusion: The positive correlations between IL4, IL17A, IL17F and IL22 in the affected skin of patients with mycosis fungoides may underlie the positive effect of phototherapy.

Karamova A.E., Vorontsova A.A., Obraztsova O.A., Nikonorova E.R., Nikonorov A.A., Deryabin D.G., Kubanov A.A.

Introduction. Dysregulation of the immune system and inflammationis associated with the pathogenesis of psoriasis andmanifestedas significant changes in cytokine profile. This fact can be used to monitor the course of the disease and its treatment. However, the results of these studies are insufficient, sometimes contradictory and require a more in-depth analysis. Aim to identify matches between cytokine profile, clinical scoresof psoriasis severity and the presence of psoriatic arthritis (PsA). Methods. Standardized clinical scores (PASI, BSA, and sPGA) were used to assess the severity of psoriasis. It was defined as moderate if 10 PASI 20 and sPGA was 23, and as severe if PASI 20 and sPGA was 45. Determination of the cytokine levelsin plasma was carried out by the multiplex immunological analysis using xMAP technology. Statistical analysis and visualization of the obtained data was carried out using RStudio for MacOS and the R programming language. Results. The total 113 patients with psoriasis vulgaris of moderate and severe severity were enrolled in the present study. On the basis of PASI score, moderate psoriasis was diagnosed in 55 (48.7%) patients and severe in 58 (51.3%) patients. PsA was diagnosed in 41 (36.3%) patients. Depends on disease severity the differences in the levels of IL-12, IL-20 and IL-22 were revealed. Significant difference in IL-6 level between patients with PsA and without it were shown. We have identified two independent cytokine networks, represented by a cluster of cytokines associated with psoriasis severity scores (IL1TNFIL-17A, IL-22, and IL-20), and a cluster which was not associated with severity (IL-21, IL-23, IL-25, IL-17F, IL-31, IL-33, IL-4, and IL-10). Conclusion. The results of the study for the first time describe the cytokine networks associated with the systemic inflammation in psoriasis; characterize the main effector cytokines determined the severity of the inflammatory response in skin and the development of PsA.

Arfenya K., Znamenskaya L., Vorontsova A., Obraztsova O., Nikonorov A., Nikonorova E., Deryabin D., Kubanov A.

An analysis of the relationship between plasma cytokines and the effectiveness of treatment with TNFαinhibitors was performed in 81 patients with moderate-to-severe psoriasis. Treatment efficacy was assessed by PASI score, and patients were classified into a positive effect (PASI≥75) and no effect group (PASI≤50). A positive effect was reached in 11 (41%) patients for etanercept, 14 (52%) for adalimumab, and 26 (96%) for infliximab. Data analysis did not show  differences in baseline TNFα levels and subsequent treatment effectiveness. The CART algorithm showed that at the baseline level of VEGF ≥ 32 pg/ml and IL17F &amp;lt; 26 pg/ml, there was an 83% probability of a positive effect. Random forest analysis showed the importance of VEGF, ICAM1, sCD40L, IL17F and IL31 baseline levels in the prediction of treatment effectiveness.   Significant differences between the groups before/after the treatment were found only for TNFα: the median values were more than 50 times higher in no effect compared with positive effect group. There were differences before/after therapy in the levels of IL20, ICAM1, IL22, IL23 in the no effect group. The treatment affected the cytokine profile in most cases regardless of the effectiveness of therapy.

Shagabieva J., Nosov N., Shpilevaja M.V., Deryabin D., Obraztcova O., Nikonorova E., Kubanov A., Solomka V.

Background. Neisseria gonorrhoeae can rapidly develop resistance to antimicrobial agents due to innate mechanisms for the acquisition of antimicrobial resistance genes. Because of the rapid formation of resistance mechanisms of N. gonorrhoeae to the antimicrobial agents used in gonococcal therapy, the risk of incurable forms of the disease is high. The purpose of the study is to to summarize the results of RU-GASP over a 16-year period and assess the trends of N. gonorrhoeae resistance to antimicrobials used in the regimens of antibiotic therapy of gonococcal infection in Russia. Materials and methods. Study Objective. The study included 5356 isolates of N. gonorrhoeae received from January 2005 to December 2021 in State Scientific Center of Dermatovenerology and Cosmetology, Moscow of the Ministry of Health of Russia under the RU-GASP program from specialized medical organizations of dermatovenerological profile of 37 subjects of the Russian Federation. Primary identification of N. gonorrhoeae was performed using bacterioscopic and bacteriological methods. The cultures identified as N. gonorrhoeae were frozen in a cryogenic medium and transported to SSCDC. Received cultures were verified by biochemical criteria on a VITEK 2 Compact analyzer. For cultures identified as N. gonorrhoeae with less than 99% probability, a time-of-flight ionization mass spectrometer MALDI Microflex (Bruker Daltonics GmbH, Germany) was used for mass spectrometric analysis. Antimicrobial susceptibility testing. Sensitivity testing of N. gonorrhoeae to six antimicrobials penicillin, spectinomycin, ceftriaxone, tetracycline, azithromycin and ciprofloxacin was performed by serial dilution in agar with determination of minimum suppressive concentrations (MSC, mg/L). N. gonorrhoeae sensitivity to antibacterial agents was evaluated according to EUCAST criteria (The European Committee on Antimicrobial Susceptibility Testing, 2022, http://www.eucast.org). Results. The study showed the absence of significant changes in the ratio of sensitive and resistant to the action of antimicrobial drugs strains of N. gonorrhoeae that is a consequence of the effectiveness of the RU-GASP program, which allowed to exclude in time from therapeutic use the drugs for which a high proportion of the identified resistant strains was observed. Conclusion. Analysis of RU-GASP results over a 16-year period confirms the use of third-generation cephalosporins (Ceftriaxone, Cefixime) as the drugs of choice for therapy of gonococcal infection, and the aminocyclic antibiotic spectinomycin as an alternative drug. The continued evolution of the molecular mechanisms of antibiotic resistance of N. gonorrhoeae dictates the need to continue the RU-GASP program.

Karamova A.E., Verbenko D.A., Vorontsova A.A., Zhilova M.B., Nikonorov A.A., Gatiatulina E.R., Znamenskaya L.F., Kubanov A.A.

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-1β, 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.

Kondrakhina I.N., Zatevalov A.M., Gatiatulina E.R., Nikonorov A.A., Deryabin D.G., Kubanov A.A.

Background. Androgenic alopecia (AGA) is the most common form of pathological hair loss with multiple micronutrient disorders involvedin its occurrence and development. Aimto evaluatethe effectiveness of personalized treatment of micronutrient deficiencies in patients with early stages of AGA and conservative therapy using a vasodilator drug minoxidil based on evidence-based medicine. Methods. A total 48 patients with stages IIV of AGA (according to the NorwoodHamilton scale) were recruited to experimental prospective clinical study evaluating the effectiveness of pharmaceutical forms of trace elements and vitamins. The primary diagnosis of micronutrient deficiency was carried out by comparing laboratory parameters of patients with AGA and 25 healthy volunteers. After that, conservative treatment with 5% topical minoxidilin AGA patients was enriched with 2-month personalized systemic supplementation of pharmaceutical forms of trace elements and vitamins. At the end of the study, the correspondence between changes in trace elements and vitamins content in the plasma and the trichogram parameters before and after conservative therapy was assessed. Results. The majority (96%) of the examined patients with AGA were characterized by mono- or polynutrient deficiencies. Personalized correction made it possible to restore the content of Se, Mg, Fe and vitamin E to the baseline levels and to achieve a significant increase in Zn, vitamin D and folic acid plasma content. The relationship between changes in the level of micronutrients and trichogram parameters was recorded only for Se (decrease in anagen hairs: r = 0.43; p = 0.037; decrease in hair density: r = 0.45; p = 0.028) and folic acid (an increase in anagen hairs: r = 0.41; p = 0.024); the positive effect of vitamin E on hair density was also detected. Conclusion. The results of the study allow to recommend a personalized treatment of folic acid and vitamin E deficiencies, with possible refusal to use the Se-containing drugs in conservative therapy of patients with the early stages of AGA.

Krol' T.A., Zinnatshina L.V., Gatiatulina E.R., Radimich A.I., Saybel O.L., Baleev D.N., Ossipov V.I.

Among representatives of the genus Arnica L., the Arnica montana L. species is the most studied and widely used for medical purposes. However, due to the fact that the A. montana species is endangered in most European countries, the possibility to use Arnica foliosa Nutt. as an alternative source of phytochemicals is being investigated. A deeper study of the chemical composition of A. foliosa extract may give the opportunity to expand the spectrum of its possible application. The purpose of the research was to perform a detailed study of the composition and content of biologically active compounds the aerial part of A. foliosa by high performance liquid chromatography with diode array detection in combination with high-resolution mass spectrometry. Sixteen phenolic compounds were detected in ethylacetate and butanol fractions of A. foliosa. There were identified thirteen derivatives of caffeoylquinic acid and three flavonoids. In the chloroform and diethyl ester fractions, phenolic compounds were absent. It was established that the ethylacetate fraction contains big amounts of two phenolic compounds – 3,4-dicaffeoylquinic and 4,5-dicaffeoylquinic acids, and eight compounds were presented in trace or very small quantities. All sixteen phenolic compounds were found in the butanol fraction, but their total content was almost 2-fold less than in the ethylacetate fraction.

Kondrakhina I.N., Verbenko D.A., Zatevalov A.M., Gatiatulina E.R., Nikonorov A.A., Deryabin D.G., Kubanov A.A.

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.

Kondrakhina I.N., Verbenko D.A., Zatevalov A.M., Gatiatulina E.R., Nikonorov A.A., Deryabin D.G., Kubanov A.A.

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%).

Tinkov A.A., Ajsuvakova O.P., Filippini T., Zhou J., Lei X.G., Gatiatulina E.R., Michalke B., Skalnaya M.G., Vinceti M., Aschner M., Skalny A.V.

Selenium (Se) homeostasis is tightly related to carbohydrate and lipid metabolism, but its possible roles in obesity development and in adipocyte metabolism are unclear. The objective of the present study is to review the current data on Se status in obesity and to discuss the interference between Se and selenoprotein metabolism in adipocyte physiology and obesity pathogenesis. The overview and meta-analysis of the studies on blood Se and selenoprotein P (SELENOP) levels, as well as glutathione peroxidase (GPX) activity in obese subjects, have yielded heterogenous and even conflicting results. Laboratory studies demonstrate that Se may modulate preadipocyte proliferation and adipogenic differentiation, and also interfere with insulin signaling, and regulate lipolysis. Knockout models have demonstrated that the selenoprotein machinery, including endoplasmic reticulum-resident selenoproteins together with GPXs and thioredoxin reductases (TXNRDs), are tightly related to adipocyte development and functioning. In conclusion, Se and selenoproteins appear to play an essential role in adipose tissue physiology, although human data are inconsistent. Taken together, these findings do not support the utility of Se supplementation to prevent or alleviate obesity in humans. Further human and laboratory studies are required to elucidate associations between Se metabolism and obesity.

Gatiatulina E.R., Sheina E.A., Nemereshina O.N., Popova E.V., Polyakova V.S., Agletdinov E.F., Sinitskii A.I., Skalny A.V., Nikonorov A.A., Tinkov A.A.

The present study aimed to assess the effect of Zn supplementation on trace element levels in the liver, serum, and hair of rats with dietary-induced non-alcoholic fatty liver disease (NAFLD). A total of 26 3-month-old female Wistar rats were divided into four groups: control, NAFLD, Zn-supplemented (227 mg/L zinc as Zn sulfate Zn(SO)4 dissolved in a drinking water), and NAFLD-Zn-supplemented. NAFLD was verified by histological assessment of liver samples. The serum was examined for routine biochemical parameters. Trace elements content was assessed using inductively coupled plasma mass spectrometry (ICP-MS). Zn treatment resulted in an improvement in liver weight and morphology. Dietary supplementation with Zn prevented NAFLD-induced decrease liver Co. The tendency to increase liver Fe in the Zn-treated group was observed. Zn treatment decreased hepatic Al and serum V levels. However, Zn administration did not affect NAFLD-induced I, Mn, and Se depletion in the liver. Hair Zn levels raised in Zn-supplemented groups. Conclusively, the results of the study indicate that Zn supplementation could have a beneficial effect in modulation of the altered trace element status and liver morphology. •Zn treatment improved liver weight and morphology in rats with NAFLD. •Zn supplementation decreased liver Al in NAFLD. •Treatment by Zn prevented depletion of liver Co. •Zn decreased serum V and increased hair Zn levels. •No effect of Zn on NAFLD-induced hepatic I, Mn and Se depletion was observed.

Yan Y., Jin L., Li J., Chen G.

Moon M.K., Lee G., Choi S., Lee I., Lee A., Kim M.J., Park S., Cho Y.H., Park Y.J., Oh S., Park J., Cho N.H., Choi K.

Pota G., Puzone A., Carrella E., Pezzella A., Luciani G., D’Errico G., Vitiello G.

Kadı A., Öner S., Yuca H., Arslan M.E., Atila A., İncekara Ü., Karakaya S.

Kandinov I., Shaskolskiy B., Kravtsov D., Larkin A., Kubanov A., Shpilevaya M., Shagabieva J., Nosov N., Gryadunov D.

IntroductionThe emergence of multidrug resistance in N. gonorrhoeae is a serious global problem, and gonorrhea may soon become an incurable disease. The aim of the study was to characterize the N. gonorrhoeae population in Russia from 2015 to 2023 and predict the potential spread of the most concerning clones.MethodsA total of 996 N. gonorrhoeae isolates were examined during the analyzed period. Ceftriaxone and azithromycin susceptibility testing were performed using the agar dilution method. Microarray-based assays and sequencing were employed to identify the genotypes and genetic markers of antimicrobial resistance.ResultsNo ceftriaxone-resistant isolates were found in Russia, however, the number of isolates with reduced susceptibility to ceftriaxone has increased to 22.6% in recent years. Since 2020, approximately 12.5% of isolates have exhibited resistance to azithromycin annually. Two clusters of isolates pose a particular threat to Russia: NG-MAST G2212, linked to MLST 1901/1902, carries a mosaic structure in the penA gene; G12302, linked to MLST 9363, contains mosaic alleles in the mtrR and mtrD genes. Additionally, two new high-risk genogroups were characterized: G18898 and G16206. Both are associated with MLST 10314 and harbor mosaic variants of penA or mtrR/mtrD. Analysis of time series data suggests that isolates with mosaic alleles are unlikely to be eradicated from the population in the near future, potentially worsening the epidemiological situation of gonorrhea in Russia.ConclusionsThe native genetic strains of N. gonorrhoeae in Russia, which are susceptible to cephalosporins and macrolides, are being progressively replaced by globally dominant lineages. To further characterize this epidemiologic shift, ongoing surveillance strategies using molecular epidemiology and the identification of genetic markers will be crucial in curbing the growth and spread of N. gonorrhoeae resistance. Such efforts are vital in ensuring the availability of effective treatments for gonococcal infection.

Karamova A.E., Vorontsova A., Nikonorov A.А., Nikonorova E.R., Kubanov А.A.

Background: Despite the proven efficacy and safety of biologics in the treatment of psoriasis (Ps), a number of patients experience heterogeneity in response to therapy in both the short-term and long-term perspectives. Objective: To identify correlations between the blood cytokine levels, clinical severity indices and the effectiveness of the IL12/IL23 inhibitor (ustekinumab) therapy. Methods: The study enrolled 25 patients with psoriasis. The severity of the disease was assessed using PASI, BSA, sPGA. The clinical efficacy of ustekinumab was determined by the percentage of PASI reduction: high (≥75%) and low efficacy (≤50%). Blood cytokine levels were determined by multiplex immunological analysis (xMAP) technology. Statistical analysis was performed using RStudio and the R programming language. Results: Moderate Ps was diagnosed in 15 patients (60%), severe - in 10 (40%). The baseline levels of IL31, sCD40L and VEGF were respectively 2.3 (p=0.018), 2.3 (p=0.010), and 2 (p=0.033) times higher in severe Ps. By the 16th week, therapy was effective in 92% of patients and was accompanied by a 3.47-fold decrease in IL31 (p=0.002) and an increase in ICAM1 and VEGF by 35.8% (p=0.026) and 4.2 times (p0.001) respectively. A correlation between ∆PASI and IL12, IL17F, IL20, IL22, IL31, sCD40L, VEGF was found. Ustekinumab significantly modified cytokine interactions and neutralized their correlation with ∆PASI. Conclusion: IL31, sCD40L and VEGF baseline levels correlate with Ps severity, IL17F, IL20 and IL31 - with ∆PASI, demonstrating their potential use in objectively determining Ps severity and predicting the ustekinumab therapy effectiveness.

Serini S., Trombino S., Cassano R., Marino M., Calviello G.

Background/Objectives. Psoriasis is a common chronic skin inflammatory disorder pathogenetically associated with genetic, environmental, and immunological factors. The hallmarks of psoriatic lesions include sustained inflammation related to alterations in the innate and adaptive immune response, uncontrolled keratinocyte proliferation, differentiation, and death, as well as dysregulated crosstalk between immune cells and keratinocytes. In search of novel therapeutic strategies based on the use of natural products and dietary components to combine to the available conventional and innovative therapeutics, we explored the anti-inflammatory, antioxidant, and immunomodulatory activities of Curcumin (CU)-based solid lipid nanoparticles (SLNs) carrying the omega-3 fatty acid linolenic acid (LNA) in an in vitro model of psoriasis that had been previously constructed and characterized by us. Methods. This in vitro model consists of differentiated in vitro THP-1 macrophages (Mφs) and NCTC-2544 keratinocytes exposed or not to conditioned medium (CM) from Mφs treated with the Toll-like receptor-7 ligand imiquimod (IMQ). Results. In Mφs, the treatment with CU-LNA-SLNs inhibited the IMQ-induced expression of proinflammatory cytokines (IL-23, IL-8, IL-6: 43%, 26.5% and 73.7% inhibition, respectively, vs IMQ-treated Mφs), as well as the hyperproliferative response (12.8% inhibition vs IMQ-treated Mφs) and the increase in cell death observed in keratinocytes treated with Mφ-derived CM (64.7% inhibition). Moreover, in the same conditions, CU-LNA-SLNs reverted to control levels of the increased keratinocyte expression of two markers of ferroptosis, a form of death recently involved in the pathogenesis of psoriasis (TFRC and MDA: 13.4% and 56.1% inhibition, respectively). Conclusions. These results suggest that CU-LNA-SLNs could inhibit psoriatic inflammation, as well as the hyperproliferation and death of keratinocytes in psoriatic lesions, and could be considered as a new possible therapeutic strategy for psoriasis to be further evaluated for the topic treatment of psoriatic skin in vivo.

Barik D., Rakhi Mol K.M., Anand G., Nandamol P.S., Das D., Porel M.

The compounds known as environmental pollutants are those that have a negative impact on the environment, the natural world, and the ecosystem. These pollutants are the result of several human activities, including waste disposal, transportation, industry, and agriculture. Pollutants in the environment have wide-ranging effects. They have possessed a long-term effect on the air, water, and soil, which causes a number of issues for the ecological systems. The emission of greenhouse pollutants is a significant factor in the alteration of global climate patterns. Additionally, the release of air pollutants such as carbon dioxide and sulfur dioxide adds to the formation of smog and poses a risk to respiratory health. Waterborne contaminants possess the potential to inflict harm upon aquatic ecosystems and pose a significant danger to the quality and safety of drinking water sources. The presence of soil contaminants has the potential to diminish the fertility of agricultural land and impede the functioning of terrestrial ecosystems. The main and extremely hazardous environmental contaminants are endocrine disruptors/pesticides/reactive dyes and inorganic toxic compounds metals, radionuclides, and metalloids. As the majority of these contaminants directly contaminate potable water, they are of great concern. Numerous studies are going on for the selective detection and removal of these pollutants from environment. In summary, it is critical to comprehend how different contaminants affect ecosystems because rising environmental pollution levels have a detrimental effect on them.

Xu W., Wen X., Fu Y., Yang J., Cui H., Fan R.

Nuclear receptor coactive 4 (NCOA4) is a specific receptor for ferritinophagy, transporting ferritin to lysosomal degradation, releasing free iron, and excessive iron levels may lead to cellular redox imbalance, contributing to cell death, predominantly ferroptosis. NCOA4 is regulated by a variety of transcriptional, post-transcriptional, translational, and post-translational modifications. Targeted modulation of NCOA4-mediated ferritinophagy has been successfully used as a therapeutic strategy in several disease models. Recent evidences have elucidated that ferritinophagy and ferroptosis played a major role in heavy metals toxicity. In this review, we explored the regulatory mechanism of NCOA4 as the sole receptor for ferritinophagy from multiple perspectives based on previous studies. The significant role of ferritinophagy-mediated ferroptosis in heavy metals toxicity was discussed in detail, emphasizing the great potential of NCOA4 as a target for heavy metals toxicity.

Sharma A., Pathania P., Hussain S., Sharma S.K.

Rezaeian M., Mohammadi S., Mohamadi M., Ahmadinia H., Mohammadi H., Ghaffarian-Bahraman A.

In most countries around the world, henna (Lawsonia inermis) has been widely used for centuries as a traditional cosmetic and therapeutic plant. However, there is a growing concern about the safety and potential toxicity associated with the use of henna. The research aimed to analyze the levels of mercury (Hg), cadmium (Cd), and nickel (Ni) in 36 henna samples (red, green, black) from both locally produced and imported products commonly used in Iran. The henna samples analysis was carried out using an atomic absorption spectrometry (AAS) system. The level of Hg in all samples was lower than 0.002 µg/g. The levels of Cd and Ni in the samples were at the ranges of 0.25 – 2.05 µg/g (mean = 0.85 µg/g) and 6.7 – 21.8 µg/g (mean = 14.35 µg/g), respectively. The level of Cd in 94.5% of samples was higher than the maximum permissible limits (0.3 µg/g) recommended by the World Health Organization (WHO). To our knowledge, this paper is the first investigation into the level of Hg, Cd, and Ni in Iran’s henna. The findings from this study showed that levels of Cd and Ni in henna samples used in Iran were high and seemed to pose a threat to health.

Gil J., Kim D., Choi S., Bae O.

Shirai M., Hara T., Kaji T., Yamamoto C.

Sarmiento-Ortega V.E., Alcántara-Jara D.I., Moroni-González D., Diaz A., Vázquez-Roque R.A., Brambila E., Treviño S.

Svagusa T., Matic N., Mirosevic V., Maldini K., Siljeg M., Milicic D., Gasparovic H., Rudez I., Urlic M., Tokic T., Ivankovic S., Tjesic-Drinkovic D., Sepac A., Muller D., Lucijanic M., et. al.

Karamova A., Znamenskaya L., Vorontsova A., Obraztsova O., Nikonorov A., Nikonorova E., Deryabin D., Kubanov A.

Background/Objectives: Psoriasis is a chronic, inflammatory, immuno-mediated cutaneous disease characterized by a prominent TNFα-IL23/IL17 immune axis. In recent years, targeted therapies have become standard practice for managing moderate-to-severe psoriasis and have demonstrated efficacy. At the same time, identifying factors associated with the success or failure of TNFα inhibitor therapy remains one of the most difficult aspects in psoriasis treatment. Methods: A clinical, non-randomized study was conducted to evaluate the impact of TNFα inhibitors on the plasma cytokine profiles in patients with moderate-to-severe psoriasis vulgaris (ICD-10 code L40.0). The patients were treated with either etanercept, adalimumab, or infliximab for 16 weeks. Plasma cytokine profiles were assessed using a BioPlex200 System. Results: By the 16th week of therapy, a positive treatment response (PASI ≥ 75) was observed in 51 patients (63%), while 30 patients (37%) showed no response (PASI ≤ 50). When using etanercept, a positive effect was observed in 11 patients (41%), in 14 patients (52%) using adalimumab, and in 26 patients (96%) using infliximab. Analysis of the baseline cytokine levels revealed no differences between the “positive effect” and “no effect” groups, except for IL20, which was 2.61 times higher in the “positive effect” group compared to the “no effect” group, suggesting its potential predictive role in the effectiveness of therapy with TNFα inhibitors. Treatment led to a decrease in IL17F, IL31, sCD40L, and VEGF for all patients, and in IL20 for the “positive effect” group. The increase in ICAM1 in the “no effect” group suggests the possible retention of active migration and the fixation of T cells in the affected skin in these patients. No significant difference in cytokine levels was observed when categorizing patients into subgroups based on the effectiveness of therapy with etanercept, infliximab, and adalimumab; only a pre- and post-treatment difference in the whole cohort was noted. A random forest model showed the importance of VEGF, sCD40L, and ICAM1. Conclusions: The baseline levels of VEGF, sCD40L, and ICAM1, as well as IL20, could serve as potential predictors of treatment effectiveness using TNFa inhibitors. However, this hypothesis requires confirmation with a larger patient population.

Wride A.M., Chen G.F., Spaulding S.L., Tkachenko E., Cohen J.M.

Biologic therapies targeting tumor necrosis factor alpha (TNF-α) (infliximab, adalimumab, certolizumab, etanercept), the p40 subunit shared by IL-12 and IL-23 (ustekinumab), the p19 subunit of IL-23 (guselkumab, tildrakizumab, risankizumab), IL-17A (secukinumab, ixekizumab), IL-17-RA (brodalumab) and both IL-17A and IL-17F (bimekizumab) have revolutionized the treatment of psoriasis. In both the short and long term, risankizumab had highest Psoriasis Area and Severity Index 90 scores compared to other oral and injectable biologics. IL-23 inhibitors had lowest rates of short-term and long-term adverse events and most favorable long-term risk-benefit profile compared to IL-17, IL-12/23, and TNF-α inhibitors.

Lidiková J., Čeryová N., Grygorieva O., Bobková A., Bobko M., Árvay J., Šnirc M., Brindza J., Ňorbová M., Harangozo Ľ., Kňazovická V.

AbstractThis study aimed to evaluate the mineral content, and content of bioactive compounds in fruits of Cornelian cherry (Cornus mas L.). Neochlorogenic acid, chlorogenic acid, caffeic acid, and rutin were determined in the samples. Vitamin C content ranged from 610.36 to 1344 mg kg−1 FW. Content of K, Ca, P, Mg, and Na in samples ranged from 1750.8 to 2645.7 mg kg−1 FW, from 281.14 to 561.62 mg kg−1 FW, from 180.38 to 294.95 mg kg−1 FW, from 68.19 to 115.43 mg kg−1 FW, and from 2.48 to 71.33 mg kg−1 FW respectively. Content of Fe, Zn, Cu, Mn, Ni, Cr, and Co in samples ranged from 2.77 to 4.88 mg kg−1 FW, from 0.49 to 0.99 mg kg−1 FW, from 0.25 to 0.53 mg kg−1 FW, from 0.07 to 0.17 mg kg−1 FW, from 0.02 to 0.13 mg kg−1 FW, from 0.01 to 0.02 mg kg−1 FW, and from 0.01 to 0.08 mg kg−1 FW respectively. Variations across cultivars were found to be statistically significant, indicating that genetics is a key factor influencing the concentration of bioactive compounds and minerals in Cornelian cherry fruits. Understanding the genetic factors influencing mineral and bioactive compound content in cornelian cherry cultivars is essential for targeted breeding programs, crop improvement, and the development of cultivars with enhanced nutritional and health-promoting attributes. This knowledge contributes to sustainable agriculture and supports the production of crops that align with consumer preferences and health trends.

Papp K.A., Lebwohl M.G., Thaçi D., Jaworski J., Kwiek B., Trefler J., Dudek A., Szepietowski J.C., Reznichenko N., Narbutt J., Baran W., Kolinek J., Daniluk S., Bartnicka-Maslowska K., Reich A., et. al.

CT-P43 is a candidate ustekinumab biosimilar in clinical development. This paper aims to demonstrate equivalent efficacy of CT-P43 to originator ustekinumab in adults with moderate to severe plaque psoriasis. This double-blind, phase III trial randomised patients (1:1) to receive subcutaneous CT-P43 or originator ustekinumab (45/90 mg for patients with baseline body weight ≤ 100 kg/> 100 kg) at week 0 and week 4 in Treatment Period I. Prior to week 16 dosing in Treatment Period II, patients receiving originator ustekinumab were re-randomised (1:1) to continue originator ustekinumab or switch to CT-P43; patients initially randomised to CT-P43 continued receiving CT-P43 (at weeks 16, 28 and 40). The primary endpoint of the trial was mean per cent improvement from baseline in Psoriasis Area Severity Index (PASI) score at week 12. Equivalence was concluded if confidence intervals (CIs) for the estimate of treatment difference were within pre-defined equivalence margins: ± 10% [90% CI; modified intent-to-treat set; Food and Drug Administration (FDA) approach] or ± 15% [95% CI; full analysis set for patients only receiving 45 mg doses in Treatment Period I; European Medicines Agency (EMA) approach]. Additional efficacy, pharmacokinetic, safety and immunogenicity endpoints were evaluated through week 52. Results to week 28 are reported here. In Treatment Period I, 509 patients were randomised (CT-P43: N = 256; originator ustekinumab: N = 253). The mean per cent improvement in PASI score at week12 was 77.93% and 75.89% for CT-P43 and originator ustekinumab, respectively (FDA approach); per the EMA approach, corresponding values were 78.26% and 77.33%. Estimated treatment differences were 2.05 (90% CI −0.23, 4.32) and 0.94 (95% CI −2.29, 4.16); equivalence was achieved for both sets of assumptions. Further efficacy parameters and pharmacokinetic, safety and immunogenicity outcomes were comparable between treatment groups, including after switching from originator ustekinumab to CT-P43. CT-P43 demonstrated equivalent efficacy to originator ustekinumab in patients with moderate to severe plaque psoriasis, with comparable pharmacokinetic, safety and immunogenicity profiles. ClinicalTrials.gov Identifier: NCT04673786; date of registration: 17 December, 2020

Bogdanova E.V., Kubanov A.A.

The paper describes changes in resources and performance of medical organizations providing medical care in the field of dermatovenereology in 20162022. The dynamics of the main rates of the service was analyzed, and the rates achieved in 2022 were compared with those before the pandemic of a new coronavirus infection. The rates of the provision of the population of the Russian Federation with dermatovenereologists, 24-hour and daytime dermatovenereological beds are presented. The analysis of the volumes of dermatovenereologic medical care dynamics provided in outpatient, inpatient and day hospital conditions was carried out. The dynamics of incidence of sexually transmitted infections is described, contribution of syphilis cases among foreign citizens to syphilis rates is presented. The changes in prevalence and incidence rates of diseases of the skin and subcutaneous tissue, as well as atopic dermatitis, psoriasis, contact dermatitis, other dermatitis, localized scleroderma, and discoid lupus erythematosus are analyzed.

Tenuta M.C., Loizzo M.R., Tundis R., Dugay A., Bouzidi C., Marie A., Acquaviva R., Cappello A.R., Deguin B.

Berry fruits are recognized as a “superfood” due to their high content of bioactive compounds and health benefits.

Oda-Yamamizo C., Mitsuda N., Milkowski C., Ito H., Ezura K., Tahara K.

AbstractAluminum toxicity is the main factor limiting the elongation of plant roots in acidic soil. The tree species Eucalyptus camaldulensis is considerably more resistant to aluminum than herbaceous model plants and crops. Hydrolyzable tannins (HTs) accumulating in E. camaldulensis roots can bind and detoxify the aluminum taken up by the roots. However, in herbaceous model plants, HTs do not accumulate and the genes involved in the HT biosynthetic pathway are largely unknown. The aim of this study was to establish a method for reconstituting the HT biosynthetic pathway in the HT non-accumulating model plant Nicotiana benthamiana. Four E. camaldulensis enzymes were transiently expressed in N. benthamiana leaves via Agrobacterium tumefaciens-mediated transformation. These enzymes included dehydroquinate dehydratase/shikimate dehydrogenases (EcDQD/SDH2 and EcDQD/SDH3), which catalyze the synthesis of gallic acid, the first intermediate of the HT biosynthetic pathway that branches off from the shikimate pathway. The others were UDP-glycosyltransferases (UGT84A25 and UGT84A26), which catalyze the conversion of gallic acid to β-glucogallin, the second intermediate. The co-expression of the EcDQD/SDHs in transgenic N. benthamiana leaf regions promoted the synthesis of gallic acid. Moreover, the co-expression of the UGT84As in addition to the EcDQD/SDHs resulted in the biosynthesis of β-glucogallin, the universal metabolic precursor of HTs. Thus, we successfully reconstituted a portion of the HT biosynthetic pathway in HT non-accumulating N. benthamiana plants. This heterologous gene expression system will be useful for co-expressing candidate genes involved in downstream reactions in the HT biosynthetic pathway and for clarifying their in planta functions.

Belinchon Romero I., Mateu Puchades A., Ribera Pibernat M., Ruiz Genao D.P., de la Cueva Dobao P., Carrascosa J.M.

Andersen C.S., Kvist-Hansen A., Siewertsen M., Enevold C., Hansen P.R., Kaur-Knudsen D., Zachariae C., Nielsen C.H., Loft N., Skov L.

For people with psoriasis, biomarkers aiding in the personalization of treatment with biologics are needed. We examined the usefulness of several biomarkers of inflammation in this respect. The neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR), and the systemic immune–inflammation index (SII) were measured in patients with psoriasis initiating TNF-α inhibitors (n = 131), IL-17/IL-17R inhibitors (n = 65), or IL-23/IL-12/23 inhibitors (n = 50). The blood levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, interferon (IFN)-γ, IL-17A, IL-6, soluble IL-6 receptor (sIL-6R), and soluble IL-6 signal transducer (sIL-6ST) were measured in patients initiating adalimumab (n = 62) or IL-17/IL-17R inhibitors (n = 24). Treatment response was defined by a psoriasis area and severity index (PASI) ≤ 2 three months after treatment initiation. Responders to TNF-α inhibitors had a lower NLR at baseline than non-responders (median and interquartile range (IQR) 2.15 (1.67–2.86) vs. 2.54 (1.88–3.55); p = 0.04). Responders to treatment with adalimumab had lower IL-6 levels at baseline than non-responders (0.99 (0.42–1.4) vs. 1.62 (0.96–2.41) pg/mL; p = 0.02). For the majority of patients, the IL-17A, IL-1β, and IFN-γ levels were below quantification limits. NLR and IL-6 may serve as predictive biomarkers of treatment response to TNF-α inhibitor therapy in patients with psoriasis.

Jiraskova Zakostelska Z., Reiss Z., Tlaskalova-Hogenova H., Rob F.

Psoriasis is a chronic, immune-mediated, inflammatory disease primarily affecting the skin. It is currently coming to light that patients with psoriasis have disrupted intestinal barrier and often suffer from comorbidities associated with the gastrointestinal tract. Moreover, there is growing evidence of both cutaneous and intestinal paradoxical reactions during biologic treatment in patients with psoriasis. This review focuses on barrier defects and changes in immune responses in patients with psoriasis, which play an important role in the development of the disease but are also influenced by modern biological treatments targeting IL-17 and TNFα cytokines. Here, we highlight the relationship between the gut–skin axis, microbiota, psoriasis treatment, and the incidence of paradoxical reactions, such as inflammatory bowel disease in patients with psoriasis. A better understanding of the interconnection of these mechanisms could lead to a more personalized therapy and lower the incidence of treatment side effects, thereby improving the quality of life of the affected patients.

Li J., Chen L., Jiang H., Li M., Wang L., Li J., Wang Y., Guo Q.

There is a lack of information on the compound profile of Cornus officinalis Sieb. et Zucc. seeds. This greatly affects their optimal utilization. In our preliminary study, we found that the extract of the seeds displayed a strong positive reaction to the FeCl3 solution, indicating the presence of polyphenols. However, to date, only nine polyphenols have been isolated. In this study, HPLC-ESI-MS/MS was employed to fully reveal the polyphenol profile of the seed extracts. A total of 90 polyphenols were identified. They were classified into nine brevifolincarboxyl tannins and their derivatives, 34 ellagitannins, 21 gallotannins, and 26 phenolic acids and their derivatives. Most of these were first identified from the seeds of C. officinalis. More importantly, five new types of tannins were reported for the first time: brevifolincarboxyl-trigalloyl-hexoside, digalloyl-dehydrohexahydroxydiphenoyl (DHHDP)-hexdside, galloyl-DHHDP-hexoside, DHHDP-hexahydroxydiphenoyl(HHDP)-galloyl-gluconic acid, and peroxide product of DHHDP-trigalloylhexoside. Moreover, the total phenolic content was as high as 79,157 ± 563 mg gallic acid equivalent per 100 g in the seeds extract. The results of this study not only enrich the structure database of tannins, but also provide invaluable aid to its further utilization in industries.

Leone G.M., Mangano K., Petralia M.C., Nicoletti F., Fagone P.

Due to the key role of tumor necrosis factor-alpha (TNF-α) in the pathogenesis of immunoinflammatory diseases, TNF-α inhibitors have been successfully developed and used in the clinical treatment of autoimmune disorders. Currently, five anti-TNF-α drugs have been approved: infliximab, adalimumab, golimumab, certolizumab pegol and etanercept. Anti-TNF-α biosimilars are also available for clinical use. Here, we will review the historical development as well as the present and potential future applications of anti-TNF-α therapies, which have led to major improvements for patients with several autoimmune diseases, such as rheumatoid arthritis (RA), ankylosing spondylitis (AS), Crohn’s disease (CD), ulcerative colitis (UC), psoriasis (PS) and chronic endogenous uveitis. Other therapeutic areas are under evaluation, including viral infections, e.g., COVID-19, as well as chronic neuropsychiatric disorders and certain forms of cancer. The search for biomarkers able to predict responsiveness to anti-TNF-α drugs is also discussed.

Lauffer F., Eyerich K.

Schlapbach C.

Pritulo O.A., Petrov A.A., Maraqa M.Y.

BACKGROUND: Currently, many researchers attach great importance in psoriasis pathogenesis to hyperproduction of vascular endothelial growth factor (VEGF) and endothelin-1, which leads to increased angiogenesis in dermis and mediates processes of immune inflammation. At the same time, possibility of using these angiogenesis biomarkers as additional indicators of immune inflammation activity and disease activity has been poorly studied. AIMS: the purpose of the study was to assess the relationship between serum concentrations of VEGF and endothelin-1, structural changes in the capillary bed according to videodermatoscopy, and severity and prevalence of skin lesions in patients with psoriasis, duration of disease, presence of nail lesions, synovitis, enthesitis and spondylitis, as well as concomitant diseases of the cardiovascular system. MATERIALS AND METHODS: The work is based on examination data analysis of 132 patients with moderate and severe psoriasis vulgaris for the period 20202022. Patients were determined the levels of VEGF and endothelin-1 in blood plasma and underwent digital dermatoscopy to study the characteristics of angiogenesis vascular loci (vascular glomeruli) in the papillary dermis. All psoriasis patients with symptoms of musculoskeletal system lesions were examined by a rheumatologist, which was supplemented by ultrasonography of the joints. RESULTS: According to the results of enzyme immunoassay, it was found that the examined patients had an increased concentration of VEGF and endothelin-1 in blood plasma compared to the control group (respectively 19.5 [4.7; 48.1] pg/ml and 274.5 [146; 439] pg/ml versus 5.2 [0.5; 9.8] pg/ml and 96.5 [32; 188] pg/ml, p=0.004 and p=0.002). It was found that an increase in plasma concentrations of VEGF and endothelin-1 correlates with an increase in density of vascular glomeruli (respectively r=0.65 and r=0.74) and the average diameter of the glomerulus (respectively r=0.58 and r=0.56). A more pronounced increase in plasma concentrations of VEGF and endothelin-1 in patients with psoriasis was noted in patients with psoriatic arthritis and in the presence of synovitis. VEGF levels were higher in patients with severe psoriasis and in patients with nail lesions. Correlation analysis showed the strongest relationship between VEGF concentration and DAS28, DLQI, PASI and NAPSI values, as well as endothelin-1 concentration and PASI, BSA and DLQI values. CONCLUSIONS: The work showed that the plasma concentration of VEGF and endothelin-1 characterizes the degree of angiogenesis expression in the psoriasis pathogenesis, reflects morphology changes in capillaries of the affected skin, and can also be used as a marker of severe psoriasis and an increased risk of developing damage to the nails and synovial membranes of the joints.