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The article offers information on the study related to influence of adalimumab on the expression profile of mRNAs and miRNAs related to IL-12 and IL-23 signal paths. Topics discussed include recommendation of adalimumab by Polish Dermatology Society for patients with moderate or severe form of psoriatic arthritis; determination of the expression pattern of mRNAs and miRNAs regulating their transcriptional activity associated with IL12/23 signaling pathway in normal human dermal fibroblast.

Background: The techniques of choice used in the treatment of extensive vascular lesions of the face are methods based on high-energy light sources, such as lasers and IPL (intense pulsed light). The techniques commonly employed to detect blood vessel abnormalities in skin primarily rely on semi-quantitative or qualitative scales. Methods: The study was conducted on a group of 38 volunteers; a series of three treatments was performed using an IPL source (Lumecca, Inmode, Israel). The vessels' response to the high-energy light was verified using the following quantitative methods: mexametric measurements, hyperspectral imaging, and directional reflectance measurements. Results: In the mexameter measurement, statistically non-significant differences were obtained in the hemoglobin content in the skin condition prior to and following multiple intense pulsed light sessions. Studies performed using a hyperspectral camera showed that at a wavelength of 580 nm, the increase in skin reflectance after the treatment was statistically significant. Total directional reflectance measurements showed that at wavelengths of 400-540 nm and 480-600 nm, following the IPL treatment, the skin reflectance increased statistically significantly. Implementing three consecutive intense pulsed light procedures appears adequate to obtain a clinically satisfactory reduction in vascular changes in the facial skin. Mexametric measurements do not enable the assessment of the reaction of blood vessels to IPL. Conclusions: Hyperspectral imaging is an effective method for the quantitative assessment of skin vascular lesions. The best results in the assessment of vascular lesions using hyperspectral imaging are obtained at wavelengths of 420 nm and 580 nm. The hemispheric directional reflectance method allows for a quick, accurate, and repeatable assessment of vascular skin changes.

Background: Simple onycholysis is a common complaint after trauma and consists in separation of the nail plate from the nail bed. If untreated, prolonged onycholysis may cause a disappearing nail bed (DNB) that leads to the shortening or narrowing of the nail plate., Objectives: This study is aimed at discussing possible treatment of chronic simple onycholysis with DNB by combined conservative methods., Methods: Simple onycholysis and DNB treatment consists of Onygen® cream application, nail bed massages, bracing procedures and nail folds taping with kinesio tape., Results: Long-lasting simple onycholysis with DNB may be fully eliminated by applying the combined pharmacological, orthonyxia and taping treatment., Conclusion: Advanced simple onycholysis, which leads to the DNB and, in consequence, to the shortening or narrowing of the nail plate, causes cosmetic discomfort for patients. A damaged nail apparatus is also more susceptible to new traumas. Even long-standing onycholysis with DNB can be successfully treated with easy-to-apply conservative methods. The key point of therapy is the use of several methods of treatment with different effects on the nail apparatus. The effects of described therapy are highly satisfactory, the only drawback being its long term, which is caused by slow growth of the nails., (© 2023 The Authors. Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

<br><b>Introduction:</b> Despite the use of highly specialized irradiation techniques in the treatment of head and neck tumors, it is still impossible to selectively destroy cancer cells without damaging normal structures, including connective tissue cells.</br> <br><b>Aim:</b> The aim of the study was to analyze the concentration of degradation markers such as collagen type I (carboxyterminal telopeptide of type I collagen; ICTP) and elastin (elastin-derived peptides; EDPs) as well as selected metalloproteinases (MMP-1, MMP-2, MMP-9) in patients with head and neck malignancies undergoing radiotherapy.</br> <br><b>Material and methods:</b> The test group consisted of 56 men, who underwent radical or palliative radiotherapy. The concentrations of ICTP, EDPs, MMP-1, MMP-2, MMP-9 were determined in three blood samples collected from patients prior to radiotherapy, immediately after its completion and 3 months after the therapy.</br> <br><b>Results</b>: Both radical and palliative radiotherapy contribute to a significant increase in the concentration of EDPs. At the time of healing of post-irradiation lesions, the level of EDPs was reduced in both groups. The ICTP concentration was not affected by radiotherapy. No significant differences were observed in the concentration of MMP-1 and MMP-2 before and after radiotherapy. Radical radiotherapy caused a statistically significant late reduction in the concentration of MMP-9. The lowest concentrations of MMP-1, MMP-2, MMP-9 in the serum of patients qualified for palliative radiotherapy were recorded in a samples collected three months post-irradiation.</br> <br><b>Conclusions:</b> The degradation markers of key extracellular matrix structural proteins may be helpful tools in the objective assessment of radiation-induced injuries to the connective tissue.</br&gt.

Background: The skin is a protective barrier of the body against external factors, and its damage leads to a loss of integrity. Normal wound healing results in a correct, flat, bright, and flexible scar. Initial skin damage and patient specific factors in wound healing contribute that many of these scars may progress into widespread or pathologic hypertrophic and keloid scars. The changes in cosmetic appearance, continuing pain, and loss of movement due to contracture or adhesion and persistent pruritis can significantly affect an individual's quality of life and psychological recovery post injury. Many different treatment methods can reduce the trauma and surgical scars. Manual scar treatment includes various techniques of therapy. The most effectiveness is a combined therapy, which has a multidirectional impact. Clinical observations show an effectiveness of manual scar therapy., Material and Methods: The aim of this work was to evaluate effectiveness of the scar manual therapy combined with complementary methods on the postoperative scars. Treatment protocol included two therapies during 30 min per week for 8 weeks. Therapy included manual scar manipulation, massage, cupping, dry needling, and taping., Results: Treatment had a significant positive effect to influence pain, pigmentation, pliability, pruritus, surface area, and scar stiffness. Improvement of skin parameters (scar elasticity, thickness, regularity, color) was also noticed., Conclusion: To investigate the most effective manual therapy strategy, further studies are needed, evaluating comparisons of different individual and combined scar therapy modalities., (© 2022 The Authors. Skin Research and Technology published by John Wiley & Sons Ltd.)

Background: MAP kinases are some of the cascades that are specialized in the cell's response to external stimuli. Their impaired functioning can be observed during the course of psoriatic arthritis. Currently, the best-known class of biological drugs is the inhibitors of the proinflammatory cytokine TNF-α, including adalimumab., Objective: The aim of this study was to assess changes in the expression of MAP kinase genes in patients with psoriatic arthritis treated with adalimumab, as well as to determine which of the analyzed transcripts could be used as a diagnostic or therapeutic target., Methods: An analysis was performed on the total RNA extracted from PBMCs of patients with psoriatic arthritis before and after three months of adalimumab therapy as well as from a control group. Changes in the expression of the mitogen-activated protein kinase genes were assessed using the HG-U133A 2.0 oligonucleotide microarray method, while the obtained results were validated using the real-time RT-qPCR method., Results: Using the oligonucleotide microarray method, 14 genes coded for proteins from the MAPK group were identified with at least a two-fold change of expression in the control group and during adalimumab therapy. Validation of the results confirmed a statistically significant decrease in the transcriptional activity of the MAP2K2 gene in the group of patients three months after the administration of adalimumab relative to the control group., Conclusion: Adalimumab therapy alters the expression of MAPK-coding genes. The assessment of the number of MAP2K2 mRNA molecules can potentially be used in diagnostic analyses or in monitoring adalimumab therapy., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Introduction: Psoriasis is classified as an inflammatory and autoimmune disease. Changes in the concentration profile of some cytokines, such as interleukin-12 (IL-12), IL-23, and IL-17, play a key role in its pathogenesis. IL-6, IL-8 and interferon- γ (IFN-γ) are also hallmark cytokines in a psoriatic cytokine network. Cytokine-blocking drugs, which are a part of the inflammatory cascade, are now increasingly popular. One of them is ustekinumab, directed against IL-12 and IL-23, but also indirectly against other interleukins, which take part in the inflammatory reaction. Due to the complexity of inflammation pathways, new molecular markers are still being sought. Regardless of the type of therapy used, they allow to determine its effectiveness, signal the lack or loss of sensitivity to treatment., Aim: To evaluate the expression profile of genes related to the inflammatory reaction - IL-6, IL-8, and IFN-γ - in patients with psoriasis, depending on the duration of ustekinumab therapy., Material and Methods: The material for the study was the PBMCs of 14 patients suffering from psoriasis who were treated with ustekinumab. Monitoring was performed after 16, 28, and 40 weeks of therapy. The gene expression of IL-6, IL-8, and IFN-γ was measured using the RT-qPCR method., Results: There was a statistically significant increase in the expression of IL-6 and IFN-γ genes in psoriasis patients, depending on the duration of ustekinumab therapy., Conclusions: The increase in mRNA copy numbers of the pro-inflammatory IL-6 and IFN-γ genes in the following weeks of therapy may suggest that patients treated with ustekinumab may progressively develop resistance to biological treatment., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2022 Termedia Sp. z o. o.)

Background: Onychocryptosis, also known as ingrown toenails or ungues incarnati, is a fairly frequent condition, with global prevalence of approximately 20%., Objectives: This study is aimed at discussing possible conservative management of severe onychocryptosis, with a case report., Methods: Conservative approach is effective in reducing or even entirely correcting underlying nail deformities. Eliminating nail fold inflammation is necessary prior to the bracing procedure. The non-surgical approach combined with proper wound treatment of the involved nail folds is a promising alternative for a growing number of patients., Results: Nail plate deformities may be largely corrected or fully eliminated. As demonstrated by our case report, even advanced stages of onychocryptosis may be effectively treated with nonsurgical modalities., Conclusion: Proper podiatric care facilitates conservative approach to management of ingrown toenails, improving the patient's overall wellbeing and eliminating pain. The prerequisite for nonsurgical correction of the nail plate is treating inflammation first. Conservative correction is more aesthetically pleasing and less emotionally disturbing to the patients than partial or complete surgical avulsion. Lesser invasiveness is an advantage especially in the case of patients with chronic comorbidities., (© 2021 Wiley Periodicals LLC.)

Introduction: Adalimumab and cyclosporine A are drugs used in moderate to severe forms of psoriasis. Despite the molecular orientation of the drugs, there is a loss of adequate cell sensitivity to the anti-cytokine therapy., Aim: To determine the changes in the gene expression profile associated with drug resistance in the culture of normal human dermal fibroblasts (NHDF) exposed to adalimumab or cyclosporine A compared to the controls., Material and Methods: NHDF was exposed to adalimumab/cyclosporine A for 2, 8, 24 h compared to the control culture. Molecular analysis was performed using mRNA and miRNA microarray techniques. The obtained results were analysed using PL - Grid infrastructure ( p < 0.05)., Results: Of the 22277 ID mRNA, 47 are associated with drug resistance, of which the change in expression of 17 mRNA ID is statistically significant ( p < 0.05). The greatest change in transcriptional activity (FC ≥ 1.3) was observed for GLO1, SLC10A3, TUFT1, STATH, ABCB1, AGTR1 . Expression of these genes can be regulated by miR-199a-5p, miR-1231, miR-34a, miR-3188, and miR-106a (except AGTR1) ., Conclusions: The analysis of changes in the expression of mRNA and miRNA related to drug resistance gives the possibility of monitoring the effectiveness of anti-cytokine therapy., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Termedia.)

Introduction: One of the examples of genes whose expression can be altered by the action of ustekinumab is TGF-β. It is a pleiotropic cytokine whose activity affects psoriatic changes and the state of homeostasis of the whole organism., Aim: To evaluate the effect of ustekinumab on the transcriptional activity of TGF-β family genes in patients with psoriatic arthritis and to check whether the results obtained can be helpful in monitoring the progress of treatment., Material and Methods: From total PBMCs obtained from peripheral blood of 14 patients with psoriatic arthritis, total RNA was isolated. The expression level of the TGF- β 1, TGF- β 2 and TGF- β 3 genes was determined by RT-qPCR in real time., Results: In all the analysed samples, the presence of mRNA of three TGF-β isoforms was quantitated in each week of therapy. TGF- β 3 and the smallest TGF- β 2 showed the highest expression. Statistically significant correlations were observed in the amount of TGF- β 1 and TGF- β 3 /µg mRNA RNA, TGF- β 2 and TGF- β 2 /µg RNA and TGF- β 3 and TGF- β 3 /µg RNA., Conclusions: Ustekinumab influences the transcriptional activity of TGF-β genes, and the changes caused have a bearing on the patient's health., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Termedia.)

Introduction: The primary goal of psoriasis treatment is to reduce the inflammatory response and associated complications. In severe cases of psoriasis that are resistant to local treatment (e.g., keratolytic preparations) and at least two types of general treatment methods (e.g., retinoids and cyclosporine A), biological therapy is used. This study aimed to assess the systemic effects of adalimumab at a given stage of treatment in patients with psoriatic arthritis and evaluate how the drug can improve the clinical condition of the patients., Material and Methods: The study group consisted of patients with diagnosed psoriatic arthritis, while the control group consisted of individuals from whom peripheral blood mononuclear cells were obtained. The effects of the administration of adalimumab were assessed by analyzing the gene expression using oligonucleotide microarrays., Result: The apoptosis process was found to be one of the overrepresented categories (the PANTHER classification system 13.1 program, overrepresentation test, p < 0.05). The dermatological indexes decreased, indicating an improvement in the clinical conditions of the patients 3 months after the first dose of adalimumab., Conclusions: We found that adalimumab affects apoptosis, which is crucial in the development and course of psoriasis. The differential gene expression in peripheral blood mononuclear cells of patients with psoriatic arthritis indicated the potential systemic effects of adalimumab therapy. The analyses of dermatological (the Psoriasis Area and Severity Index, body surface area and Dermatology Life Quality Index) and inflammatory (Biernacki's reaction) parameters revealed the effectiveness of the therapy., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2021 Termedia & Banach.)

Competing Interests: The authors declare no conflict of interest.

Background: Ingrowing Nail is an ailment in the toe area. This problem is observed in 20% of the population, in all age groups, but most often occurs in teenagers and young adults. The process of ingrowing nail stimulates natural defense mechanisms of the body in the form of inflammation and severe pain., Aims: The aim of this paper was to make the VHO-Osthold® Perfect buckle effective as an alternative to nail plate surgery and to determine the patient's comfort during this method of treatment., Patients/methods: A descriptive case study conducted in a 15-year-old patient who had ingrowing nails in the big toes of both feet., Results: It has been shown that the VHO-Osthold® Perfect buckle therapy constitutes an effective method for ingrowing nails and one in a few conservative methods in orthonyxia, as an alternative to surgery., Conclusions: The study and clinical experience confirm that the therapy of ingrowing nails with the VHO-Osthold® Perfect buckle is painless and noninvasive. This treatment can be safely and effectively carried out by a qualified podiatrist or cosmetologist in podological practice., (© 2020 Wiley Periodicals LLC.)

Introdcution: Through interaction with receptors TNFR1 and TNFR2, TNF-α activates a signal path, which exacerbates an inflammatory process, constituting an inseparable element of psoriasis., Aim: To evaluate changes in the expression of TNF- α, TNFR1, TNFR2 during the 4-year-long adalimumab therapy in psoriatic patients, searching for the correlation between molecular and clinical markers. In addition, the role of miRNAs was analysed., Material and Methods: Whole blood and serum samples of psoriatic patients treated with adalimumab constituted material for the study. Changes in the expression of TNF- α and its receptors were evaluated with the use of the RTqPCR method and MALDI ToF mass spectroscopy, PASI, BSA, DAS28 indexes were used for the clinical analysis of the patients, while the role of miRNA molecules was determined basing on microrna.org database., Results: Different TNF-α expression patterns were determined in patients with observed resistance to the medicine. We found that there is a correlation between the molecular markers of an inflammatory process and the clinical indexes. The bioinformatic analysis indicates the potential role of miRNAs in the regulation of expression of the analysed genes. Changes in the profile of TNF-α during adalimumab therapy are significantly determined by the individual variability and susceptibility to the biological medicine or its loss., Conclusions: TNF-α seems to be a useful marker to evaluate the efficacy of therapy and occurring resistance to the medicine. A complex mechanism for the regulation of the analysed gene expression was underlined, which involved the potential role of miRNAs., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 Termedia.)

Aim: The aim of the study was to assess of sTNFαR1 concentration in the serum of patients with localized scleroderma (in comparison with a control group)., Material and Methods: This was a prospective study. The patients with localized scleroderma were divided into two groups: 21 persons treated with PUVA therapy and 20 persons treated with procaine penicillin. In the case of the patients treated with intramuscularly administered procaine penicillin (dose: 2,400,000 IU/day), achievement of a total dose of at least 30 million IU/day was considered as the end of the therapy. In the group of patients treated with photochemotherapy, the single initial dose during a PUVA session was 0.5 J/cm 2 and it was increased by 0.5 J/cm 2 every other day to reach the maximum value of 10 J/cm 2 , depending on the clinical condition. The study involved three sessions a week., Results: sTNFαR1 concentration in the serum of patients with localized scleroderma was significantly higher in comparison with the control group and correlated with the skin damage index. The difference in the determined particle level was higher in the group of patients undergoing photochemotherapy (median: 106.25 ng/ml) than in the group taking penicillin (median: 81.50 ng/ml). Patients treated with PUVA sessions demonstrated a greater decrease in sTNFαR1 concentration and an improvement of the clinical condition after therapy completion., Conclusions: The obtained results suggest a potential role of sTNFαR1 in the pathogenesis of localized scleroderma., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2020 Termedia Sp. z o. o.)

Introduction: Searching for new therapeutic possibilities constitutes a challenge for modern medicine and an answer to better understanding of molecular mechanisms of pro-inflammatory diseases. The JAK-STAT pathway plays an important role in the inflammatory processes, which is supported by the fact that its inhibitors are used to treat, for instance, psoriasis and rheumatoid arthritis., Aim: To determine whether the epigenetic mechanisms - methylation of gene promotion regions and miRNAs may serve as a new therapeutic strategy for JAK-STAT pathway inhibition., Material and Methods: Basing on MethPrimer (plus CpG Island Prediction) program and microrna.org database of the said mechanism in the regulation of the JAK-STAT signalling pathway, the gene expression was performed, indicating or excluding the possibility of their use as new potential therapeutic strategies., Results: A different number of CpG islands (CGI) for each gene (JAK1-4 CGI; JAK2-2 CGI; JAK3-5 CGI, TYK2-6 CGI; STAT1-2 CGI; STAT2-1 CGI; STAT3-3 CGI; STAT5A-4 CGI; STAT5B-3 CGI) might be a new therapeutic goal. What is more, our results show that genes associated with JAK-STAT signalling pathways can be regulated by miRNAs (JAK1-42 miRNAs; JAK2-47 miRNAs; JAK3-15 miRNAs, TYK2-4 miRNAs; STAT1-17 miRNAs; STAT2-30 miRNAs, STAT3-36 miRNAs, STAT4-15 miRNAs; STAT5A-10 miRNAs; STAT5B-23 miRNAs)., Conclusions: The epigenetic mechanisms of the regulation of the JAK-STAT signalling pathway gene expression constitute a promising new therapeutic strategy for treatment of those diseases, during which disorders are observed in gene expression models of the analysed signalling pathway., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2020 Termedia Sp. z o. o.)

Background: Dermatofibroma (DF) is a common benign skin lesion in a majority of cases located on the legs or upper limbs. The etiology of DF is still unclear., Objectives: Reflectance confocal microscopy features of DF were described., Methods: Forty patients with DF diagnosis confirmed by dermoscopy were examined using reflectance confocal microscopy VivaScope 1500 from March 2018 to April 2019., Results: DF was more common in females (80%) than males (20%). Thirty-six lesions (90%) were located on the limbs while four (10%) were on the trunk. Dermoscopically, 18 lesions (45%) revealed typical features: central white area with a brown network in the periphery. Twenty-two DFs (55%) were found with a central white patch and globular-like structures, surrounded by a thin brown network. In reflectance confocal microscopy, all revealed a typical honeycombed pattern, although in some cases (30%), streaming was observed. In two lesions (5%) in epidermis, few dendritic cells were observed, and one DF revealed roundish pagetoid cells (2.5%). The dermoepidermal junction (DEJ) in all lesions was abounded in dilated vessels. The most common observable feature of DF was bright "rings" composed of monomorphic, regular cells surrounding dark dermal papillae. In five lesions (12.5%), rings were "double" because of exceptionally pigmented DF., Conclusion: Reflectance confocal microscopy enables us to describe microscopic features of DF. There are four confocal microscopic features observable in each DF: in the epidermis, normal honeycombed pattern, sometimes with local streaming, in DEJ, edged papillae, bright rings, and dilated vessels., (© 2020 the International Society of Dermatology.)

Apoptosis is a natural physiological process involving programmed cell death. Thanks to this process, it is possible to maintain the homeostasis of the body and the immune system. Dysfunctions of this mechanism lead to development of autoimmune diseases such as psoriasis; these diseases are chronic and treatment is extremely difficult. In psoriasis (a skin disease), apoptosis disorders are manifested by keratinocyte proliferation dysfunction. Autoimmune diseases coexisting with psoriasis include multiple sclerosis, autoimmune thyroid disease, and diabetes, but the common pathogenesis of these diseases is not fully understood. Given the heterogenous nature and chronic and recurrent course of psoriasis, the selection of an effective therapeutic strategy is still a problem. This literature review was focused on the process of apoptosis as a factor in the development of autoimmune diseases, with particular emphasis on psoriasis. The work also includes a review of therapeutic methods of psoriasis based on the latest literature.

Background: The human skin microbiome is represented by bacteria, fungi, viruses, and mites., Aims: Every human being possess their own unique skin microbiome because intrinsic and environmental factors have a significant impact on the quality and quantity of microorganism. Every site of the body is a separate microbial niche., Patients: The feet are one of the most unique and heterogeneous microbial niches of human body with areas that differ by skin thickness, anatomical features, distribution of sweat glands, pH, and the availability of oxygen., Results: Healthy skin of the foot is inhabited by Corynebacteriaceae, Micrococcaceae, Propionibacteriaceae, Actinobacteria, Clostridiales, Lactobacillaceae, Streptococcaceae, Enterobacteriaceae, Moravellaceae, Neisseriaceae, Pastereullaceae, and Proteobacteria. The most common fungi present on the feet are Malassezzia, Cryptococcus, Aspergillus, Rhodotorula, Epicoccum, Saccharomyces, Candida, Epidermophyton Microsporum, and Trichophyton., Conclusions: The disturbance of the foot microbiome causes dysbiosis and may lead to pitted keratolysis, fungal, and viral infections or even to protothecosis., (© 2020 Wiley Periodicals, Inc.)

Biological drugs are an alternative to treatment of psoriasis and psoriatic arthritis. Adalimumab is a representative of the anti-TNF group. The underlying of this disease is a cellular homeostasis disorder-apoptosis. Many proteins are involved in the apoptosis induction pathways, including those from the BCL-2 family. The aim of the study was to perform a transcriptional analysis of the genes coding selected proteins from the BCL-2 family in patients treated with adalimumab therapy, and to determine the direction of these changes. The test materials were peripheral blood mononuclear cells. The cells were obtained from 20 patients with psoriatic arthritis who were being treated with adalimumab (study group) and 20 healthy volunteers (control). The gene expression profile was determined using the real-time quantitative reverse transcription polymerase chain reaction technique. Statistically significant changes were observed in the expression level of the BNIP3, BNIP3L, and BCL2L1 genes (p < .05) during a 24-month observation of therapy. We indicated that adalimumab therapy has an impact on the expression of the analyzed genes, which may constitute a new class of molecular markers for assessing the effectiveness of a therapy. It appears that the BNIP3L gene could be used as a potential diagnostic marker of psoriasis., (© 2020 Wiley Periodicals LLC.)

Introduction: Adalimumab and etanercept are drugs used in anti-TNF therapy in patients with psoriasis and psoriatic arthritis. Despite the molecular targeting of these drugs, the loss of pharmacological response to treatment is observed in patients. The development of personalized medicine makes it possible to use not only clinical parameters of disease severity, but also molecular marker systems., Aim: The aim of the study was to evaluate the changes in TNF- α, TNFR1 , and TNFR2 expression in relation to parameters of disease severity (PASI, BSA, DAS28) in patients treated with adalimumab and etanercept. We have attempted to determine whether changes in the TNF- α, TNFR1 , and TNFR2 expression profile may be a useful molecular marker of the therapeutic potential of anti-TNF drugs., Material and Methods: The study group consisted of 3 patients initially treated with adalimumab, followed by etanercept. The control group included 20 healthy volunteers. The expression profile of TNFR1 and TNFR2 was determined at the mRNA level, while TNF- α expression was evaluated at the transcriptome and proteome levels using the RT-qPCR method (transcriptional activity assay) and MALDI-TOF MS (protein level assessment)., Results: Depending on the drug, different expression profiles of the studied cytokines are observed., Conclusions: The obtained data indicate that TNF- α, TNFR1 , and TNFR2 may be useful markers of the efficacy of anti-TNF therapy, thus complementing clinical parameters., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2020 Termedia Sp. z o. o.)

Background: Psoriasis is a multifactorial autoimmune disease, which underlies the abnormalities of the apoptotic process. In cases of psoriasis and psoriatic arthritis, biological treatment is used. This study aimed to determine any changes in the expression of the genes associated with apoptosis in patients with psoriatic arthritis treated with adalimumab and to assess any phenotypic modifications based on changes in dermatological indexes., Methods: The study included 20 patients with psoriatic arthritis treated biologically and 20 healthy volunteers. The research material consisted of peripheral blood mononuclear cells (PBMCs) from which the total RNA was isolated. Changes in the gene expression were determined using oligonucleotide microarrays and RT-qPCR. The clinical condition was assessed based on selected indicators: PASI, BSA [%], DAS28, and DLQI, which were determined every 3 months., Results: There were changes in the expression of genes associated with apoptosis. Significant differences were found for ROCK1, RhoA, and LIMK2 expression profiles in PBMCs. At the initial stage of treatment, a decrease in the PASI and BSA rates was observed. At the later stages, the values of these indicators increased once again. There were correlations between the changes in these genes' expression and the dermatological markers., Conclusion: Adalimumab influences the expression of genes related to apoptosis and the values of dermatological indicators of patients. Changes in the expression level of genes associated with apoptosis suggest that ROCK1, RhoA, and LIMK2 may be genes that can potentially be indicators of treatment effectiveness and lack of response to biological treatment.

Psoriasis is a chronic, recurrent, inflammatory, and proliferative skin disease. Its etiology has not yet been fully assessed, but undoubtedly it is a multifaceted disease. The key role in its pathomechanism is played by genetic, immunologic, and environmental factors and stress. If traditional methods of psoriasis treatment (phototherapy, methotrexate, retinoids, cyclosporine A) fail, we reach for the following biopharmaceuticals - infliximab, etanercept, adalimumab, or ustekinumab. However, genetic engineering progress discovers new possibilities - the pending clinical trials involve IL-17, IL-23 antagonists, PDE4 and -3 and -1. Psoriasis etiopathogenesis mainly involves the IL-17A, IL-17F, and IL-17A/F subtypes, which affect the keratinocytes. The biological therapy molecularly oriented with the antagonists of interleukin 17 is based mainly on the influence onto the cytokine in the manner that prevents it from binding with the receptor. Three biopharmaceuticals are currently under third phase studies: two fully humanized antibodies neutralizing IL-17 - ixekizumab and secukinumab, and one human monoclonal antibody, brodalumab. The below work will be devoted to the analysis of possible undesirable symptoms, which were observed during the studies. We will try to review the latest literature concerning the most important clinical trials conducted in many centers., (© 2019 The International Society of Dermatology.)

It is believed that IL-17 is involved in the signaling pathways of nuclear factor κB (NFκB) and mitogen-activated kinases (MAPKs). Adalimumab, a full anti-TNF-α monoclonal antibody, was used for treatment of moderate to severe psoriasis. This study aimed to investigate the effect of adalimumab on changes in the expression of genes associated with IL-17 signaling pathways in normal human dermal fibroblast (NHDF) culture. NHDFs treated with adalimumab at 2, 8, and 24 hr were compared with those of control. Microarray technique and PANTHER program were used to determine the expression of genes. The number of mRNA IDs differentiating the culture displayed on adalimumab in comparison with the control culture (-3.0 < FC > + 3.0) was as follows: H-2-32 mRNA ID, H-8-3 mRNA ID, H-2 and H-8-47 mRNA ID, H-8 and H-24-1 mRNA ID. Analysis by the PANTHER program indicated that adalimumab significantly affects the six signaling pathways and 19 biological processes associated with IL-17. The strongest changes in the expression profile concerned pathway genes associated with the chemokine and cytokine signaling pathway, the gonadotropin-releasing hormone receptor pathway, and the CCKR signaling map., (© 2019 Wiley Periodicals, Inc.)

The psoriasis therapy consists of the inhibition of cytokines involved in inducing and development of this disease. The aim of the study was to evaluate the changes in the expression of genes related to the oxidative stress phenomenon in the culture of normal human dermal fibroblasts of Normal Human Dermal Fibroblasts (NHDF) exposed to adalimumab. NHDF culture was exposed to adalimumab for 2-, 8-, and 24-hr periods. The control consisted of the same cells not exposed to adalimumab. The oligonucleotide microarrays HG-U133A 2.0 were used to analyze the changes in gene expression in NHDF culture. Analysis showed that there are 3,881 ID mRNA involved in the induction and development of oxidative stress, the expression of which changes significantly due to the exposure of NHDF cells to adalimumab (p < .05) among 1,369 ID mRNA of them. These include genes associated with apoptosis, the p38 MAPK pathway and the PDGF pathway, and above all with pathways not yet classified. Studies have shown that two genes: NR4A2 and IL1RN, whose expression has changed the most, expressed as Fold Change (FC) seem to be the most promising molecular markers to monitor therapy and loss of cell sensitivity to treatment., (© 2019 Wiley Periodicals, Inc.)

Molecular analysis is key to a better understanding of drug resistance during therapy. The aim of this study was to evaluate changes in the expression of tumor necrosis factor α (TNF-α), interleukin (IL)-IL12A, IL12B, IL23A, interferon gamma (IFN-γ) in psoriatic patients during 84 days of treatment and TNF-α on the protein level. The study group consisted of 32 psoriatic patients during cyclosporine A therapy. The molecular analysis was made by using real-time reverse transcription polymerase chain assay (RTqPCR) and MALDI ToF mass spectroscopy three times: after 0, 42, 84 days of treatment. Statistically significant differences (p < .05) in transcriptional activity were observed for genes: TNF-α (0 vs. 42nd days p = .006; 0 vs. 84th days p = .005), IL23A (0 vs. 42nd days p = .041), IFN-γ (0 vs. 42th days p = .040; 0 vs. 84th days p = .041), IL17 (0 vs. 42nd p = .000003 0 vs. 84th p = .001650), IL12A (0 vs. 42nd p = .0047 vs. 84th p = .0063). The expression of TNF-α was downregulated during therapy, IL23A was upregulated during CsA treatment, while the expression of IFN-γ and IL17 were higher after 42 days and lower after 84 days compared to 0 days of CsA treatment. It seems that TNF-α, IL12A, IL23A, IFN-γ, and IL17 can be useful complementary molecular markers to assess the efficacy of psoriasis treatment., (© 2019 Wiley Periodicals, Inc.)

The aim of this study was to assess changes in the expression of STAT1, STAT3, STAT4, SOCS2, and IL17 in psoriatic patients under ustekinumab treatment and in healthy volunteers. The study group consisted of 14 patients suffering from psoriasis vulgaris qualified for ustekinumab therapy (4 women, 10 men) The control group consisted of 14 healthy volunteers (7 women, 7 men), their whole blood was used as a material in this study. A quantitative reverse transcription polymerase chain assay was used to amplify analyzed genes. To indicate the differences in expression of selected genes in the test and control groups, the Kruskal-Wallis and the post hoc Dunn's test was carried out. After 40 weeks of observation of the effectiveness of ustekinumab in patients with psoriasis, the expression of STAT1, STAT3, STAT4, IL17, and SOCS2 was silenced. Statistic differences in expression were observed for STAT3 (40 vs. 0 weeks, p < .05; 0 week vs. C, p < .05) and SOCS2 (0 week vs. C, p < .05). Patients with psoriasis vulgaris have higher levels of STAT1, STAT3, STAT4, SOCS2, and IL17 expression compared to healthy individuals. On the other hand, the treatment of ustekinumab lasting 40 weeks caused a decrease in the transcriptional activity of the analyzed genes., (© 2019 Wiley Periodicals, Inc.)

Metabolic diseases concurrent with psoriasis may considerably affect the intensity of its symptoms and therapy efficacy. Cyclosporine A (CsA) is one of the medicines used in conventional therapy of psoriasis. The aim of the study was to determine whether Diabetes 2 and metabolic syndromes influence the efficacy of the CsA therapy in psoriatic patients. The sample group was composed of 32 patients with diagnosed moderate to severe forms of psoriasis vulgaris. The group was divided into subgroups, with regard to concurrently occurring Diabetes 2 and metabolic syndromes. The subgroups were composed of as follows: with diabetes-7 patients, without diabetes-25, with metabolic syndrome-15, without concurrent metabolic syndrome-17, with a metabolic syndrome without diabetes-8 and with both a metabolic syndrome and diabetes-7 patients. The efficacy of therapy was evaluated in each subgroup on the basis of the following scales: PASI, BSA, DLQI on the day of therapy commencing, after 42 and 84 days of the CsA therapy. The statistical analysis was performed with the use of STATISICA 12 (Cracow, Poland; p < .05). The following tests were used: The ANOVA Friedeman test, the posthoc test for ANOVA Friedeman test, the Mann-Whitney U test. We observed clinical improvement measured with PASI BSA scales in each subgroup. The patients themselves also reported improved comfort in their lives, which is confirmed by the lower score in the DLQI scale after 42 and 84 days of the pharmacotherapy. Differences in the values of each scale in a given subgroup turned to be statistically significant. The biggest differences occur after the first 42 days of therapy and they last in the later period of observations. We did not determine any statistically significant differences as a response to treatment in the subgroups subject to comparison. Diabetes and a metabolic syndrome concurrent with psoriasis vulgaris do not affect the efficacy of CsA therapy, which indicates no necessity to modify the standard dosage of the medicine and therapy regime., (© 2019 Wiley Periodicals, Inc.)