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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.

The aim of this study was to evaluate the influence of medial femoral condyle (MFC) free flap harvest on donor site muscle strength and kinematic parameters of gait. The study included 30 patients treated for head and neck squamous cell carcinoma who underwent reconstruction with an MFC free flap. In each case, the donor site was the left thigh. A dynamometer was used to measure muscle strength, in isokinetic bilateral mode and with concentric contraction for the extension/flexion knee pattern, at 18 months postoperative. In addition, kinematic data were obtained and evaluated. On statistical analysis, no significant difference in muscle strength of the quadriceps muscle was found between the left involved and right uninvolved lower extremities (P = 0.124). Also, when comparing hamstring strength, no statistically significant difference was found between the left involved and right uninvolved sides (P = 0.210). Moreover, spatiotemporal gait parameters did not differ significantly between the involved and uninvolved legs (all P > 0.05), and no differences in kinematic or kinetic parameters were observed. This study reports the effects of MFC free flap harvest on the knee muscle strength and locomotion of patients. For most biomechanical parameters investigated, there was no effect (positive or negative)., Competing Interests: Competing interests None., (Copyright © 2024 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

BACKGROUND Aquafilling® is a soft-tissue filler used in various procedures, including breast plastic surgery. Proponents claim it to be safe and effective without causing serious adverse effects. This study aimed to describe histological changes in breast tissue resulting from potentially harmful effects of Aquafilling®. MATERIAL AND METHODS Tissue samples were collected from 16 patients who underwent surgical removal of Aquafilling®. Histopathological evaluations were performed on hematoxylin and eosin-stained slides, with photographs captured using an Olympus BX 43 light microscope and an XC 30 digital camera at 40×, 100×, and 400× total magnification. RESULTS Inflammatory infiltrates, mainly consisting of macrophages and lymphocytes, were observed in the images. Tissue necrosis was visible in some areas. Fibrosis foci and blood vessels with thickened walls and detached endothelium were identified within mammary adipose tissue. CONCLUSIONS Due to the variety of clinical symptoms and presence of inflammation in all examined women, we recommend histopathological examinations for all cases of Aquafilling® surgical removal. The examination should include information on the extent of inflammation, progression of adipose and muscle tissue damage, and assessment of fibrosis severity. This will help clinicians make informed decisions about Aquafilling® use in patients and improve patient outcomes.

The aim of this prospective cohort study was to explore the effect of statins on long-term respiratory symptoms and pulmonary fibrosis in coronavirus disease 2019 (COVID-19) patients with diabetes mellitus (DM). Patients were recruited from three tertiary hospitals, categorized into Statin or Non-statin groups, and assessed on days 0, 28, and 90 after symptoms onset to record the duration of symptoms. Pulmonary fibrosis was scored at baseline and follow-up time points by high-resolution computed tomography scans. Each group comprised 176 patients after propensity score matching. Data analysis revealed that the odds of having cough and dyspnea were significantly higher in the Non-statin group compared to the Statin group during the follow-up period. Overall, there was no significant difference in the change in pulmonary fibrosis score between groups. However, Non-statin patients with > 5 years of DM were more likely to exhibit a significantly higher fibrosis score during the follow-up period as compared to their peers in the Statin group. Our results suggest that the use of statins is associated with a lower risk of developing chronic cough and dyspnea in diabetic patients with COVID-19, and may reduce pulmonary fibrosis associated with COVID-19 in patients with long-term (> 5 years) DM., (© 2023. The Author(s).)

BACKGROUND This retrospective population study identified 385 191 positive real-time reverse transcription-polymerase chain reaction (RT-PCR) tests for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from a single laboratory in Katowice, Poland, from April 2020 to July 2022. MATERIAL AND METHODS The material was nasopharyngeal, nasopharyngeal swab or bronchial lavage, and bronchoalveolar lavage (BAL) to confirm or exclude SARS-CoV-2 infection with the RT-PCR technique. Personal data are use according to the Provisions on the Protection of Personal Data by the Gyn-Centrum laboratory. RESULTS In 9 months of 2020, the number of SARS-CoV-2 results was 88 986; in 2021, it was 168 439, and in the first 7 months of 2022, it was 12 786. In 2020, the highest number of positive results was recorded in the third quarter (83 094 cases); 2021, in the 1st, 2nd, and 4th quarters (58 712; 37 720; and 71 753 cases, respectively), and in 2022, in the 1st quarter (127 613 cases) of the year. A positive result was observed more often in women and people aged 30-39, followed by those 40-49 years. Patients aged 10-19 years comprised the smallest population of SARS-CoV-2-positive cases. CONCLUSIONS In the Polish population studied, from April 2020 to July 2022, the detection rates of SARS-CoV-2 positivity were significantly higher for women than for men and in the 30-49 age group for both sexes. Also, the infection detection rate of 385 191 out of 1 332 659 patient samples, or 28.9%, supports that the Polish society adhered to public health recommendations for infection control during the COVID-19 pandemic.

Previous studies have not completely elucidated the role of the histaminergic system in the pathogenesis of psoriasis. This study aimed to evaluate the effects of adalimumab and cyclosporine A on the expression of histaminergic system-related genes and miRNAs regulating these genes in bacterial lipopolysaccharide A (LPS)-stimulated human keratinocyte (HaCaT) cells. HaCaT cells were treated with 1 µg/mL LPS for 8 h, followed by treatment with 8 µg/mL adalimumab or 100 ng/mL cyclosporine A for 2, 8, or 24 h. Untreated cells served as controls. The cells were subjected to ribonucleic acid (RNA) extraction and microarray, quantitative real-time polymerase chain reaction, and enzyme-linked immunosorbent assay analyses. Statistical analysis was performed using the Statistica 13.0 PL (StatSoft, Cracow, Poland) and the Transcriptome Analysis Console programs (Affymetrix, Santa Clara, CA, USA) ( p < 0.05). The differential expression of the following two miRNAs was not affected in LPS-stimulated cells upon treatment with cyclosporine A or adalimumab: hsa-miR-583 (downregulated expression), involved in the regulation of histamine receptor 1 - HRH1 (overexpression); has-miR-1275 (downregulated expression), involved in the regulation of histamine receptor 1 - HRH3 (overexpression) and Solute carrier family 22 member 3 - SLC23A2 (downregulated expression)). Adalimumab and cyclosporine A modulated the histaminergic system in HaCaT cells in vitro . However, further studies are needed to elucidate the underlying mechanisms. Abbreviations: (-) - downregulated in comparison to the control, (+) - overexpression in comparison to the control, ACTB - β-actine, ADA - Adenosine deaminase, ADCYAP1 - Adenylate Cyclase Activating Polypeptide 1, BMP - bone morphogenetic protein, bp - base pair, cAMP - adenosine 3' 5'-cyclic monophosphate, CBX7 - Chromobox protein homolog 7, cDNA - double-stranded complementary DNA, CSA - cyclosporine A DAG - diacylglycerol, DIAPH - Diaphanous related formin 1, DNMT - DNA methyltransferases, DRD2 - Dopamine receptor D2, EDN1 - Endothelin 1, EDNRA - Endothelin receptor type A, ELISA - Enzyme-linked immunosorbent assay, EZH2 - Enhancer of zeste homolog 2, FC - fold change, GABRB1 - Gamma-aminobutyric acid (GABA) A receptor, alpha 1, GABRB2 - Gamma-aminobutyric acid (GABA) A receptor, alpha 2, GABRB3 - Gamma-aminobutyric acid (GABA) A receptor, alpha 3, HaCaT - Human adult, low-calcium, high-temperature keratinocytes, HIS - Human Histamine, HLAs - human leukocyte antigens, HNMT - Histamine N-methyltransferase, HNMT - Histamine N-Methyltransferase, HRH1 - histamine receptor 1, HRH2 - histamine receptor 2, HRH3 - histamine receptor 3, HRH4 - histamine receptor 4, HTR6 - 5-Hydroxytryptamine Receptor 6, IGF1 - Insulin-like growth factor 1, IL10 -interleukin 10, IL12 -interleukin 12, IL6 - interleukin 6, IP3 - inositol 1,4,5-triphosphate, LPS - bacterial lipopolysaccharide A, LYN - LYN Proto-Oncogene, Src Family Tyrosine Kinase, MAPKs -mitogen-activated protein kinases, miRNA - micro RNA, MMP2 - matrix metalloproteinase-2, NHDF - Normal Human Dermal Fibroblasts, NHEK - Normal Human Epidermal Keratinocytes, OCT3 - organic cation transporter 3, PANTHER - Protein ANalysis THrough Evolutionary Relationships Classification, PBS - phosphate-buffered saline, PI3K-AKT - phosphatidylinositol 3-kinase-protein kinase B, PIP2 - phosphatidylinositol 4,5 bisphosphate, PMSF - phenylmethylsulfonyl fluoride, PSORS1- psoriasis susceptibility gene 1, qRT-PCR - quantitative Reverse Transcription Polymerase Chain Reaction, RNA - ribonucleic acid, RNAi - RNA interference, RTqPCR - Real-Time Quantitative Reverse Transcription Reaction, SLC223A2 - Solute carrier family 22 member 3, SNX -Sorting nexin, SOX9 - SRY-Box Transcription Factor 9, TGF-α - transforming growth factor α, TGF-β - transforming growth factor beta, TNF-α - tumor necrosis factor alpha, TP53 - tumor protein 5 z, VAMP2 - Vesicle associated membrane protein 2.

Background: The aim of the study was to evaluate the variances in the expression pattern of mRNAs and miRNAs related to the EMT in the Ishikawa (histological grade 1; G1), EC-1A (histological grade 2; G2), and KLE (histological grade 3; G3) cell cultures under cisplatin treatment., Methods: Endometrial cancer cell lines were exposed to 75.22 mg (an average concentration of the drug used in patients with endometrial cancer) for 12.24 and 48 hours in comparison to the untreated cells (control). The molecular analysis included: extraction of total RNA, microarray analysis (mRNA and miRNA), RTqPCR, and the ELISA assay., Results: Out of 226 mRNAs associated with the EMT, the number of mRNAs differentially expressed in endometrial cancer cell cultures treated with cisplatin compared to a control culture was as follows: Ishikawa line - 87 mRNAs; EC-1A - 84 mRNAs; KLE - 71 mRNAs (p<0.05). The greatest changes in the Ishikawa line treated with the drug compared to the control were noticed for mRNA STAT1 TGFβ1, SMAD3, FOXO8, whereas in EC-1A they were mRNA TGFβ1, BAMBI, SMAD4, and in KLE mRNA COL1A1, FOXO8, TGFβ1. The analysis also showed that miR-106a, miR-30d, miR-300 are common for all cell lines used in this experiment., Conclusion: Cisplatin changes the expression profile of genes associated with EMT in endometrial cancer cell lines. It seems that the expression pattern of TGFβ1 might be a promising, supplementary molecular marker of the effectiveness of cisplatin therapy. The analysis showed that miR-30d, miR-300, and miR-106a are involved in the regulation of the expression of EMT-related genes., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Introduction: Tumor necrosis factor-α (TNF-α) plays an extremely important role in the regulation of hypothalamicpituitary-adrenal axis. It is believed that chronic inflammation is the main cause of cancerogenesis and TNF-α plays a significant role in both of these processes. Unfortunately, the function of TNF-α in human adrenal steroidogenesis has not been explained enough., Aim: To evaluate the changes in transcriptional activity of STAR , CYP11A1 , CYP11B1 , and CYP11B2 in H295R cell line exposed to TNF-α., Material and Methods: NCI-H295R, human adrenocortical cell line was exposed to human recombinant TNF-α at the concentrations ranging from 0.001 to 10 nM for 3, 12, 24, and 48 h. Cells not exposed to TNF-α were the control of this experiment. RTqPCR assay was used to determine the changes in the expression of genes encoding STAR , CYP11A1 , CYP11B1 , and CYP11B2., Results: The highest differences between stimulated and non-stimulated cells were observed in the expression of STAR (FC = +2.2; 0.01 nM of TNF-α; 48 h); CYP11A1 (FC = +3.5; 0.1 nM of TNF-α; 24 h); CYP11B1 (FC = +7.0; 10 nM of TNF-α; 48 h); CYP11B2 (FC = +2.5; 10 nM of TNF-α; 48 h). Statistically significant differences ( p < 0.05) in the expression were found only for CYP11A1. The interaction effect between genes was also noticed ( p < 0.05)., Conclusions: The research showed the impact of TNF-α on the expression of the key genes encoding enzymes involved in adrenal steroidogenesis. Different expression patterns of was observed, depending on time and TNF-α concentration increased synthesis of this pro-inflammatory cytokine may intensify adrenal steroidogenesis., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2021 Termedia Sp. z o. o.)

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.)

Competing Interests: The authors declare no conflict of interest.

Background: It is important to understand the molecular mechanisms involved in cancer drug resistance and to study the activity of new drugs, e.g. salinomycin., Objective: The purpose of the study was to analyze changes in the expression of genes associated with drug resistance in the Ishikawa endometrial cancer cell line when treated with salinomycin. In addition, changes in the level of miRNA potentially regulating these mRNAs were evaluated., Materials and Methods: Endometrial cancer cells were treated with 1 μM of salinomycin for 12, 24 and 48 hours periods. Untreated cells were a control culture. The molecular analysis consists of mRNA and miRNA microarray analysis and the RTqPCR technique., Results: The following was observed about the number of mRNAs differentiating the cell culture exposed to the drug compared to a control culture: H-12 vs. C - 9 mRNAs, H&#95;24 vs. C - 6 mRNAs, and H&#95;48 vs. C - 1 mRNA. It was noted that 4 of the 9 differentiating mRNAs were characteristic for 12 hours of exposure to salinomycin and they correspond to the following genes: TUFT1, ABCB1, MTMR11, and MX2. After 24 hours, 2 mRNAs were characteristic for this time of incubation cells with salinomycin: TUFT1 and MYD88 and after 48 hours, SLC30A5 could also be observed., Discussion: The highest differences in expression were indicated for TUFT1, MTMR11, and SLC30A5. The highest influence probability was determined between TUFT1 and hsa- miR-3188 (FC + 2.48), MTMR11and has-miR-16 (FC -1.74), and between SLC30A5 and hsa-miR-30d (FC -2.01)., Conclusion: Salinomycin induces changes in the activity of mRNA and miRNA participating in drug resistance; however, the observed changes in character are the expected result of anti-cancer treatment., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Autophagy plays a dual role of tumor suppression and tumor promotion in colorectal cancer. The study aimed to find those microRNAs (miRNAs) important in BECN1 , LAMP2 , and PINK1 regulation and to determine the possible role of the epigenetic changes in examined colorectal cancer using an in silico approach., Methods: A total of 44 pairs of surgically removed tumors at clinical stages I‒IV and healthy samples (marginal tissues) from patients' guts were analyzed. Analysis of the obtained results was conducted using the PL-Grid Infrastructure and Statistica 12.0 program. The miRNAs and CpG islands were estimated using the microrna.org database and MethPrimer program., Results: The autophagy-related genes were shown to be able to be regulated by miRNAs ( BECN1 -49 mRNA, LAMP2 -62 mRNA, PINK1 -6 mRNA). It was observed that promotion regions containing at least one CpG region were present in the sequence of each gene., Conclusions: The in silico analysis performed allowed us to determine the possible role of epigenetic mechanisms of regulation gene expression, which may be an interesting therapeutic target in the treatment of colorectal cancer.

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.)

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.

Background: Ustekinumab is a monoclonal antibody that shows the ability to bind to subunit p40, common for interleukin 12 (IL-12) and IL-23, which prevents the activation of the JAK STAT signaling pathway., Objectives: The objective of the study was to evaluate the efficacy of therapy that uses anti-IL-12/23 medicine in patients with psoriasis vulgaris, based on the disease clinical progression indices (Psoriasis Area and Severity Index (PASI), Dermatology Life Quality Index (DLQI) and Body Surface Area (BSA)) and to determine the possibilities of using changes in the expression profiles of tumor necrosis factor α (TNF-α), tumor necrosis factor receptor (TNFR1) and TNFR2 as molecular markers showing the response to ustekinumab therapy., Material and Methods: The group under study was composed of 14 patients (10 men and 4 women, aged 49.3 ±10.2 years) with diagnosed psoriasis vulgaris, treated with ustekinumab. The group was divided into subgroups because of the selected 3 stages of therapy. The control group consisted of 20 healthy volunteers (11 men and 9 women, aged 46 ±10 years). The 120-week long observation involved a clinical assessment of the patients (PASI, BSA and DLQI), based on the following scheme: 0-4-12 weeks of the observation. The analysis of molecular changes in the TNF-α, TNFR1 and TNFR2 expression profiles was performed with the quantitative reverse-transcription polymerase chain reaction (RT-qPCR) method, using the patients' full blood. The statistical analysis was performed with STATISTICA v. 12.0 PL (StatSoft Inc., Tulsa, USA) with the level of statistical significance p < 0.05., Results: Gradually reduced PASI, BSA and DLQI values were observed during anti-IL-12/23 therapy. An increased level of the TNF-α transcription activity was observed in the analyzed group when compared to the control. Correlations between the clinical and molecular parameters were also indicated., Conclusions: Ustekinumab constitutes an efficient and safe form of pharmacotherapy in psoriasis vulgaris. We did not observe any reduced efficacy of the treatment when reclassifying patients for the therapy. Tumor necrosis factor α, TNFR1 and TNFR2 may serve as supplementary markers of molecular response to the medicine.

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.)

Endometrial cancer develops as a result of abnormal cell growth associated with uncontrolled cell proliferation, excessive activation of signaling pathways and miRNA activity. The aim of this study was to determine the expression profile of genes associated with cell proliferation and to assess which miRNAs can participate in the regulation of their expression. The study enrolled 40 patients with endometrial cancer and 10 patients without neoplastic changes. The expression profile of genes associated with cell proliferation and the expression profile of miRNAs were assessed using microarrays. RT-qPCR was performed to validate mRNA microarray results. The mirTAR tool was used to identify miRNAs that regulate the activity of genes associated with cell proliferation. Decreased expression of IGF1 and MYLK , as well as SOD2 overexpression, were observed in endometrial cancer using both mRNA microarrays and RT-qPCR. Microarray analysis showed low levels of NES and PRKCA , but this was only partially validated using RT-qPCR. Reduced activity of MYLK may be caused by increased miR-200c, miR-155 and miR-200b expression. Cell proliferation is disturbed in endometrial cancer, which may be associated with an overexpression of miR-200a, miR-200c, and miR-155, making it a potential diagnostic marker.

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.)

BACKGROUND SEMA3B is known as an inhibitor of angiogenesis and cell proliferation. During carcinogenesis, the loss of SEMA3B function is observed, which results in the progression of neoplastic changes. The aim of this study was to evaluate the expression profile of SEMA3B in endometrial cancer (G1-G3) in comparison to the control group and to assess whether the observed changes in expression could become a molecular marker in endometrial cancer. MATERIAL AND METHODS The study group consisted of 45 patients diagnosed with endometrial cancer (G1, 17; G2, 15; G3, 13). The control group included 15 patients. SEMA3B expression was assessed using the immunohistochemical method. Statistical analysis was carried out using the Statistica 12 PL program (StatSoft, USA). It included the Kruskal-Wallis test and post hoc Dunn's test (p<0.05). RESULTS Statistically significant differences in the level of SEMA3B expression were observed between all analyzed groups. The expression pattern of SEMA3B was as follows: cancer cells G1>G2>G3; endothelial cells: G3>G1>G2; stromal cells: G2>G1>G3. CONCLUSIONS Analysis of the SEMA3B expression profile shows the complexity of neoplastic transformation, which confirms the different expression of SEMA3B in endometrial cancer cells and endothelial cells. The present results and data in the literature data suggest that SEMA3B expression indicates the progression of carcinogenesis in the context of endometrial cancer.

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.)

The molecular mechanism of ustekinumab action involves an interruption of signaling pathways activated by IL-12/23. The aim of this paper was to evaluate the efficacy of the anti-IL12/23 therapy in seven psoriatic patients by assessing changes in the values of psoriasis area and severity index (PASI), dermatology life quality index (DLQI), body surface area (BSA) indexes, and an analysis of changes in the mRNA expression profile of genes IL12A, IL12B, IL23A during three 40-week long observation periods. The clinical (PASI, DLQI, BSA indexes) and molecular (RTqPCR for IL12A, IL12B, IL23A) analyses were performed on the day of ustekinumab therapy initiation, 4 weeks post first administration, and every 12 weeks thereafter. The statistically significant differences were observed only during Stage I for values of PASI (p = 0.0134), DLQI (p = 0.01299), BSA (p = 0.0355). During the subsequent stages, we observed lower values of PASI, BSA indexes, which suggests that the lesions are less intensified than at the moment of the therapy commencing. The relationship between the selected genes was observed: IL23A>IL12A>IL12B. In conclusion, the aforementioned clinical and molecular analysis suggests the efficacy of ustekinumab therapy in patients with psoriasis vulgaris can be analyzed with the PASI, BSA, DLQI indexes, and changes in the expression of selected genes. The analysis of IL12A, IL12B, IL23A expression may serve as a valuable supplementation for the therapeutic methods currently used to evaluate the degree of disease progression and treatment efficacy., (© 2019 Wiley Periodicals, Inc.)

Background: Psoriasis course involves increased secretion of pro-inflammatory cytokines, among others, a beta transforming growth factor (TGFβs) and its receptors. Cyclosporine A (CsA), an immunosuppressive medicine with the molecular mechanism of operation connected with the properties of cell cycle suppression, is often used in the treatment of severe forms of psoriasis. The efficacy of therapy is assessed based on the disease clinical progression indexes - Psoriasis Area and Severity Index (PASI), body surface area (BSA), and Dermatology Life Quality Index (DLQI). The aim of the study was the evaluation of the efficacy of the CsA treatment of patients with psoriasis vulgaris, based on the clinical parameters and an assessment of the expression profiles of TGFβs and TGFβRs, depending on the concurrent diabetes and metabolic syndrome., Methods: The group under study composed of 32 patients (15 with the metabolic syndrome, seven with diabetes) treated with CsA for 84 days. The molecular analysis included extraction of RNA, assessment of TGβF1-3, TGFβRI-III gene expression with the use of the RTqPCR method. The clinical assessment of the effects of this pharmacotherapy involved evaluation of the parameters: PASI, BSA, DLQI before therapy commencement, on the 42nd and 84th days of therapy., Results: A statistically significant change in the transcription activity of TGFβ1 in patients with and without diabetes (P = 0.018) and patients with and without metabolic syndrome (P = 0.023) was shown that on the 84th day of therapy., Conclusions: TGFb1 may be claimed as the supplementary molecular marker to evaluate the efficacy of CsA therapy. It seems that systemic diseases have an effect on the efficacy of the applied pharmacotherapy and the course of psoriasis., (© 2018 The International Society of Dermatology.)

Background: Vascular endothelial growth factor (VEGF)-C, -D, and VEGF receptor-3 are proteins characterized as crucial for tumor lymphangiogenesis. It is accompanied by angiogenesis during wound healing, but also in the neoplastic process. The research studies have shown that the lymphatic system plays a key role in the progression of carcinogenesis., Objective: The aim of this study was to evaluate changes in the expression of VEGF-C, VEGF-D and VEGFR-3 in different grades of endometrial cancer (G1-G3)., Methods: The study included 45 patients diagnosed with endometrial cancer (G1=17; G2=15; G3=13) and 15 patients without neoplastic changes. The expression of VEGF-C, VEGF-D, and VEGFR-3 was assessed using microarray technique and immunohistochemistry. Statistical analysis was performed using the one-way ANOVA and Tukey's post-hoc test., Results: Statistically significant changes in the expression at the transcriptome level were found only in the case of VEGF-C (G1 vs. C, fold change - FC = -1.15; G2 vs. C, FC = -2.33; G3 vs. C, FC = - 1.68). However, VEGF-D and VEGFR-3 were expressed at the protein level. Analysis of VEGF-D expression showed that the optical density of the reaction product in G1 reached 101.7, while the values in G2 and G3 were 142.7 and 184.4, respectively. For VEGF-R3, the optical density of the reaction product reached the following levels: 72 in control, 118.77 in G1, 145.8 in G2, and 170.9 in G3., Conclusion: An increase in VEGF-D and VEGFR-3 levels may indicate that VEGF-D-dependent processes are intensified along with the dedifferentiation of tumor cells. The lack of VEGF-C expression in endometrial cancer samples may suggest that this tumor is characterized by a different mechanism of metastasis than EMT. Our study emphasizes that when analyzing the metastatic potential of cancer, the expression of more than one factor should be taken into account., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: In the course of neoplastic diseases, a reduction in SEMA3F expression is observed, which translates into an increase in the proliferative and proangiogenic potential of cells forming the tumor and the surrounding microenvironment., Objective: The aim of this study was to determine the changes in SEMA3F level in endometrial cancer depending on its grade., Methods: The study material consisted of tissue samples: 15 without neoplastic changes (control group) and 45 with endometrial cancer (G1, 17; G2, 15; G3, 13; study group). SEMA3F expression was assessed using the immune-histochemical method., Results: The expression of SEMA3F was observed in the control group (Me = 159.38) and in the study group (G1, Me = 121.32; G2, Me = 0; G3, Me = 130.37). Differences between each grade and control and between individual grades were statistically significant. There were no significant correlations between SEMA3F expression and weight and Body Mass Index (BMI). The reduced SEMA3F expression in tumor tissue compared to healthy tissue indicates that this protein plays key roles in proliferation and angiogenesis., Conclusion: We found that depending on the severity of the disease, cancer adopts different survival strategies, where SEMA3F plays an important role. As a molecular marker, SEMA3F is not sensitive to weight and BMI., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Neuropilins (NRPs) participate in many processes related to cancer development such as angiogenesis, lymphangiogenesis and metastasis. Although endometrial cancer is one of the most common gynecological cancers, it has not been studied in terms of NRPs expression., Objective: The aim of this study was to investigate the potential utility of NRPs as important factors in the diagnosis and treatment of endometrial cancer., Methods: Our study consisted of 45 women diagnosed with endometrial cancer at the following degrees of histological differentiation: G1, 17; G2, 15; G3, 13 cases. The control group included 15 women without neoplastic changes. The immunohistochemical reactions were evaluated using light microscopy., Results: We did not detect the expression of NRP-1 and NRP-2 in the control group. NRP-1 expression was found exclusively in cancer cells. It was higher in G2 and G3 and reached about 190% of G1. NRP-2 expression was observed in the endothelium and was similar across all three cancer grades. In cancer cells, NRP-2 expression increased with the degree of histological differentiation., Conclusion: NRP1 and NRP2 are candidates for complementary diagnostic molecular markers and promising new targets for molecular, personalized anticancer therapies., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: EDIL3 is an extracellular matrix protein that plays a key role in angiogenesis. Changes in the pattern of its expression also affect cellular processes and the tumor microenvironment. Elevated level of EDIL3 is considered an unfavorable prognostic marker of survival., Objective: The aim of this study was to evaluate the changes in EDIL3 expression in endometrial cancer at various degrees of its differentiation (G1-G3) and to discuss its potential role as a molecular diagnostic marker and therapeutic target., Methods: The study group consisted of 45 patients with endometrial cancer: G1, 17; G2, 15; G3, 13. The control group (C) included 15 patients without neoplastic changes. The expression of EDIL3 was assessed using immunohistochemistry. Statistical analysis was performed using the Statistica 12 PL software (p<0.05)., Results: Analysis of EDIL3 expression showed that the average optical density of the reaction product in G1 reached 130% of the control, while the values in G2 and G3 were 153% and 158%, respectively. Regardless of the endometrial cancer grade, an increase in EDIL3 level was observed compared to the control., Conclusion: In our study, we demonstrated overexpression of EDIL3 protein in endometrial cancer. Differences in expression between degrees of tumor differentiation suggest the potential of using changes in EDIL3 level as a new complementary diagnostic marker and target for anti-angiogenic therapy., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Introduction: Psoriasis is a chronic, immunologic, multi-factor inflammatory skin disease, strongly associated with a higher level of a number of cytokines, such as isoforms of transforming growth factor β (TGF-β1-3) and its receptors (TGF-βRI-III). One of the most popular and important drugs used to treat this disease is cyclosporin A (CsA)., Aim: The aim of this study was to investigate the expression of genes encoding the transforming growth factor (TGF)-β isoforms and receptors of the cytokine TGF-βRs in psoriatic patients during an 84-day long observation of the effects of cyclosporin A therapy. It made an attempt to determine the usefulness of testing mRNA expression of TGF- β 1 - 3 and its receptors TGF- β RI-III as the supplementary molecular markers of lost sensitivity to the medicine., Material and Methods: The study group consisted of 32 patients with psoriasis (20 men and 12 women) treated with cyclosporin A. The changes in expression patterns of TGF- β 1-3 and TGF- β RI-III were performed by real-time quantitative reverse transcription PCR (RTqPCR)., Results: The expression of TGF- β 1-3 and TGF- β RI-III were detected in the whole period of therapy with CsA. Changes in transcriptional activities of TGF- β 1-3 and TGF- β RI-III during pharmacotherapy were observed. Differences in the expression of these genes were found before and after 42 and 84 days of using CsA., Conclusions: The changes in expression profiles of TGF- β 1-3 and TGF- β RI-III during CsA therapy can be a useful molecular marker of lost sensitivity to the medicine.

Autophagy is a highly conserved mechanism of self-digestion that removes damaged organelles and proteins from cells. Depending on the way the protein is delivered to the lysosome, four basic types of autophagy can be distinguished: macroautophagy, selective autophagy, chaperone-mediated autophagy and microautophagy. Macroautophagy involves formation of autophagosomes and is controlled by specific autophagy-related genes. The steps in macroautophagy are initiation, phagophore elongation, autophagosome maturation, autophagosome fusion with the lysosome, and proteolytic degradation of the contents. Selective autophagy is macroautophagy of a specific cellular component. This work focuses on mitophagy (selective autophagy of abnormal and damaged mitochondria), in which the main participating protein is PINK1 (phosphatase and tensin homolog-induced putative kinase 1). In chaperone-mediated autophagy, the substrate is bound to a heat shock protein 70 chaperone before it is delivered to the lysosome. The least characterized type of autophagy is microautophagy, which is the degradation of very small molecules without participation of an autophagosome. Autophagy can promote or inhibit tumor development, depending on the severity of the disease, the type of cancer, and the age of the patient. This paper describes the molecular basis of the different types of autophagy and their importance in cancer pathogenesis., Competing Interests: CONFLICTS OF INTEREST The authors declare no conflicts of interest.

Introduction: Tumour necrosis factor (TNF-α) is one of the main cytokines participating in inflammation and immune response. Biological effects of the cytokine action, mediated by two receptors: TNFRSF1A and TNFRSF1B involve activation of many signal paths, thus change the transcription activity of many genes. The mechanism of action of an anti-TNF medicine consists in blocking TNF-α though preventing activation of signal paths., Aim: To single out mRNA and microRNA genes relating to TNF-α signal paths, the expression of which could indicate sensitivity of cells to the medicine in question., Material and Methods: The material used in the research consisted in the cell line of regular human skin fibroblasts NHDF (CC-2511 Lonza, Basel, Switzerland) exposed to adalimumab with a concentration of 8.00 μg/ml of the medium for 2, 8 and 24 h, compared with the control material, i.e. non-stimulated cells. Molecular analysis was performed using the oligonucleotide expressive micro-matrices technology HG-U133A, miRNA 2.0 Array micro-matrices and RTqPCR., Results: mRNA: BIRC5, MAP3K4, ZFAND5, JUN differentiate cells exposed to the anti-TNF medicine, regardless of the time of cell/medicine incubation. TNF-α transcription activity is reduced during exposure of NHDF cells to adalimumab. miRNA regulating transcription activity of the said 4 mRNA and miRNA related to TNF-α and its receptors was also singled out., Conclusions: It was ascertained that adalimumab has therapeutic potential and affects genes engaged in signal paths activated by TNF-α. The results indicate the TNF-α usefulness as the molecular, supplementary marker in diagnostics and control of treatment effects., Competing Interests: The authors declare no conflict of interest.

Objective: The aim of this study was to evaluate the influence of adalimumab on expression profile of genes associated with the histaminergic system in Normal Human Dermal Fibroblast (NHDF) cells stimulated with 8.00  μ g/ml of adalimumab and the identification of miRNAs regulating these genes' expression., Methods: NHDFs were cultured with or without the presence of adalimumab for 2, 8, and 24 hours. The expression profile of genes and miRNA were determined with the use of microarray technology., Results: Among 22283 ID mRNA, 65 are associated with the histaminergic system. It can be observed that 15 mRNAs differentiate NHDFs cultures with adalimumab form control. The analysis of miRNAs showed that, among 1105 ID miRNA, 20 miRNAs are differentiating in cells treated with adalimumab for 2 hours, 9 miRNA after 8 hours, and only 3 miRNAs after 24 hours., Conclusion: It was also determined that miRNAs play certain role in the regulation of the expression of genes associated with the histaminergic system. The results of this study confirmed the possibility of using both genes associated with this system as well as miRNAs regulating their expression, as complementary molecular markers of sensitivity to the adalimumab treatment.

Background: Endoglin is a marker of active, proliferating endothelial cells of blood vessels. In many cancers, it is present in both peripheral vessels and vessels located inside the tumor. Endoglin is more specific and sensitive compared to other tumor angiogenesis markers. It is suggested that endoglin can be considered a reliable marker of disease outcome., Objective: The aim of the study was to assess the expression of endoglin and to determine its potential usefulness as a complementary molecular marker of endometrial cancer., Method: The study included 60 women who underwent hysterectomy: 45 with endometrioid endometrial cancer (study group) and 15 without neoplastic changes (control group). The study group was further divided according to the degree of histological differentiation: G1, 17; G2, 15; and G3, 13. The expression of endoglin was determined immunohistochemically with mouse anti-Endoglin monoclonal antibody. The obtained reactions were evaluated using light microscopy., Results: Analysis of endoglin expression in endothelium showed that it reached 145% of the control. In G2, we observed that the endoglin level decreased and was similar to the control, while in G3 it increased and was even higher than in G1. In cancer cells, endoglin expression increased with the grade of endometrial cancer., Conclusion: Endoglin can be considered a valuable complementary molecular marker, allowing to visualize the advancement of the cancer process, including endometrial cancer., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objective: The aim of this study was to evaluate the influence of adalimumab on the expression pattern of genes associated with JAK/STAT signaling pathway in Normal Human Dermal Fibroblast (NHDF) cells stimulated with 8 µg/ml of adalimumab and the identification of miRNAs regulating these genes' expression., Method: NHDFs were cultured with or without the presence of adalimumab for 2, 8, and 24h. The microarray technology was used to determine expression profile of mRNAs and miRNAs., Results: Out of 22283 ID mRNA, 37 are associated with the JAK/STAT signaling pathway. It can be observed that 18 mRNAs differentiate NHDFs cultures with adalimumab from control. The analysis of miRNAs showed that, among 1105 ID miRNAs, 20 miRNAs are differentiating in cells treated with adalimumab for 2h, 9 miRNAs after 8h, and only 3 miRNAs after 24h., Conclusion: It can be observed that miRNAs play an extremely important role in the regulation of the expression of genes associated with JAK/STAT signaling pathway. The results of this study show the possibility of using changes in mRNAs and miRNAs profile expression, as complementary molecular markers of adalimumab treatment effectiveness., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Background/aims: Psoriasis, an autoimmune diseases of the skin, characterized by patches of abnormal/inflammed skin, although not usually life-threatening, it causes severe discomfort, esthetic impairments, and may lead to impaired social functions and social withdrawal. Besides UV-phototherapy, various anti-inflammatory treatments are applied, depending on the severity of symptoms. In 2008, adalimumab (fully humanized human anti-TNF antibody) was launched for the treatment of psoriasis. In the quest to better understand the pathomechanism of adalimumab's therapeutic effects, and the acquired resistance to the drug, we have investigated how its administration affect the regulation of the expression of selected caspases, including those activated by inflammosome., Methods: The research was initially carried out on normal human dermal fibroblasts (NHDF) treated with adalimumab for 2, 8 and 24 hours in vitro. Then, expression profile of genes encoding caspases and their regulatory micro-RNAs was determined with the use of oligonucleotide microarray. The validation of the microarray results was carried out by qRT-PCR. The in vitro study was followed by ex-vivo investigation of adalimumab's effects on the expression of caspase-6 in blood of the psoriatic patients. The samples were collected before, and 2 hours after adalimumab's administration and the analysis was determined by qRT-PCR., Results: The result of the analysis indicated that introduction of adalimumab to the NHDF culture resulted in the change of the transcription activity of genes encoding caspases and genes encoding miRNAs. The analysis revealed 5 different miRNA molecules regulating the expression of: CASP2, CASP3 and CASP6. There were no statistically significant differences in the expression of gene encoding caspase-6 in the patients' blood before and 2 hours after the anti-TNF drug administration., Conclusion: We have found that adalimumab administration affects caspases expression, thus they may be used as molecular markers for monitoring the therapy with the use of an anti-TNF drugs, including adalimumab. It is likely that the mechanisms responsible for changed expression profiles of genes encoding caspase-2,-3, and -6, may be caused by the upregulation of the respective microRNA molecules. Increased expression of genes encoding specific caspases may induce inflammatory processes, as well as trigger apoptosis. Furthermore, the proapoptotic activity of caspases may be enhanced by miRNA molecules, which exhibit proapoptotic function. The overexpression of such miRNAs was observed in our study., (© 2018 The Author(s). Published by S. Karger AG, Basel.)

Background: The aim of the study was to evaluate the changes in the expression of genes - TNF-α, IFN-γ, depending on the time and concentration of IL-12 used to expose the Normal Human Dermal Fibroblast (NHDF) cells., Methods: The material for the study included NHDF exposed to IL-12 in various IL-12 concentrations (1/10/100 ng/ml) and exposure time 0.5h, 1h, 2h, 4h, 8h, 24h, compared to the control. Changes in gene expression were evaluated with the use of the RTqPCR method. The statistical analysis was performed with the use of Statistica 12.5 PL The role of genes of the JAK-STAT signaling pathway in the induction of the inflammatory process was determined with the use of the PANTHER overrepresentation test., Results: Regardless of the time of NHDF exposure and the IL-12 concentrations used, we observed changes in the expressions of TNF-α and IFN-γ. Increased expression of one transcript involves the decreased expression of the other. We assessed that genes of the JAK-STAT signaling pathway are engaged in 6 biological processes, 8 molecular functions, 6 signaling pathways., Conclusion: The conducted studies indicate that conclusions about the intensity of the inflammatory process, and the efficacy of the anti-cytokine therapeutic strategy, may be made on the basis of the TNF-α, IFN-γ expression., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)