The rapid progress of genetic engineering furthermore opens up new prospects in the therapy of this difficult-to-treat disease. IL-23 inhibitors, phosphodiesterase 4 (PDE4) inhibitors, and Janus kinase (JAK) inhibitors are currently encouraging further research. Two drugs which are IL-23 inhibitors are now in phase III of clinical trials. The aim of the action of both drugs is selective IL-23 inhibition by targeting the p19 subunit. Guselkumab is a fully human monoclonal antibody. Tildrakizumab is a humanized monoclonal antibody, which also belongs to IgG class and is targeted to subunit p19 of interleukin 23 (IL-23). Phosphodiesterase inhibitors exert an anti-inflammatory action and their most common group is the PDE4 family. PDE4 inhibits cAMP, which reduces the inflammatory response of the pathway of Th helper lymphocytes, Th17, and type 1 interferon which modulates the production of anti-inflammatory cytokines such as IL-10 interleukins. The Janus kinase (JAK) signaling pathway plays an important role in the immunopathogenesis of psoriasis. Tofacitinib suppresses the expression of IL-23, IL-17A, IL-17F, and IL-22 receptors during the stimulation of lymphocytes. Ruxolitinib is a selective inhibitor of JAK1 and JAK2 kinases and the JAK-STAT signaling pathway. This article is a review of the aforementioned drugs as described in the latest available literature.

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.

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.

Background: Autophagocytosis is a biological process involving the controlled distribution of cell fragments and organelles in order to obtain an additional source of energy. LAMP3 (lysosome-associated membrane protein 3) is a heavily glycosylated integral membrane protein located mainly in the lysosomal membrane. Recent studies have shown that it participates in tumor metastasis and drug resistance. Its main role is contribution to tumor cells proliferation, migration and invasion. The aim of this study was to determine changes in transcriptional activity of LAMP3 at various stages of colorectal cancer. In addition, an attempt was made to select miRNAs potentially regulating LAMP3 expression using bioinformatic databases. Methods: The study was conducted on healthy colon samples and colon cancer samples in four stages. Molecular analysis included the extraction of total RNA, purification of the obtained extracts, expression profile analysis using oligonucleotide microarray technique and in silico determination of miRNAs potentially regulating the LAMP3 expression. Results: The level of LAMP3 expression is higher in colorectal adenocarcinoma cells than in non-cancerous cells and depends on the stage of the disease. Conclusions: LAMP3 may promote cancer progression, metastasis and cause the resistance to treatment.

Wstęp: Bóle kręgosłupa lędźwiowo-krzyżowego są obecnie jedną z najczęściej występujących dolegliwości bólowych wśród osób starszych. Za powstawanie bólów kręgosłupa bardzo często odpowiedzialne są zwyrodnienia, przeciążenia, choroby krążka międzykręgowego i osłabienie aparatu więzadłowego kręgosłupa.Materiał i metody: Badania zostały przeprowadzone wśród 60 pensjonariuszy Domu Pomocy Społecznej w Szczecinie z przewlekłymi dolegliwościami bólowymi odcinka lędźwiowo-krzyżowego. Przedział wiekowy wynosił 56–85 lat. W sposób losowy dokonano podziału na dwie 30-osobowe grupy (grupę badaną, gdzie została naklejona aplikacja KinesioTaping, oraz grupę kontrolną – bez aplikacji). Do oceny stopnia odczuwanego bólu użyto wizualno-analogowej skali VAS w formacie poziomej skali cyfrowej w zakresie 0–10, na której pensjonariusze zaznaczali natężenie odczuwanego bólu. W badaniu ruchomości kręgosłupa i tułowia zmierzono za pomocą centymetra zgięcie, wyprost, nachylenie i rotację. Rozpatrując zakres ruchu nachylenia z uwzględnieniem płci badanych, można zauważyć, że poprawa nastąpiła u mężczyzn w grupie badanej w zakresie nachylenia w obie strony.Wyniki: U wszystkich badanych, którym zaaplikowano Kinesio-Taping na okolicę lędźwiowo-krzyżową, nastąpiło zmniejszenie dolegliwości bólowych według skali VAS (p ≤ 0,001). Nastąpiła również istotna poprawa w zakresie: rotacji w prawą stronę (p ≤ 0,05), zgięcia ocenianego testem „palec–podłoga” (p ≤ 0,01) i ruchu wyprostu (p ≤ 0,01). Nie odnotowano różnic istotnych statystycznie pomiędzy grupą badaną a grupą kontrolną.Wnioski: KinesioTaping jest korzystną metodą redukującą dolegliwości bólowe oraz wpływającą na poprawę zakresu ruchów kręgosłupa w odcinku lędźwiowo-krzyżowym u osób starszych.