Background. In the treatment of moderate to severe psoriasis, cyclosporine A (CsA) conventional therapy is used and biological, anti-cytokine treatment using, for example, anti-TNF drug—adalimumab. Aim. This study aimed at investigating the effect of CsA and adalimumab on the profile of mRNAs and protein expression associated with transforming growth factor β (TGFβ) pathways in human keratinocyte (HaCaT) culture previously exposed to lipopolysaccharide (LPS). Materials and Methods. HaCaT culture was exposed to 1 ng/ml LPS for 8 hours+8 μg/ml adalimumab for 2, 8, and 24 hours or 1 ng/ml LPS for 8 hours+100 ng/ml CsA for 2, 8, and 24 hours and compared to the control culture. Sulphorodamine B cytotoxicity assay was performed. The expression profile of mRNA related to TGFβ paths was indicated by microarray and RTqPCR analyses. The ELISA test was used to analyze changes on the proteome level. Statistical analysis consisted of ANOVA analysis and the post hoc Tukey test (p<0.05). Results. The cytotoxicity test showed that LPS, adalimumab, and cyclosporine in the concentration used in this experiment did not have any cytotoxicity effect on HaCaT cells. The largest fold changes (FC) in expression in (∣FC∣>4.00) was determined for TGFβ1-3, TGFβRI-III, SKIL, SMURF2, SMAD3, BMP2, BMP6, JAK2, UBE2D1, SKP2, EDN1, and PRKAR2B (p<0.05). In addition, on the protein level, the direct changes observed at mRNA were the same. Conclusion. Analysis of the microarray expression profile of genes associated with TGFβ signaling pathways has demonstrated the potential of cyclosporin A and adalimumab to induce changes in their transcriptional activity. The anti-TNF drug seems to affect TGFβ cascades to a greater extent than cyclosporin A. The obtained results suggest that the regularity of taking the drug is important for the efficacy of psoriasis therapy.
The main aim of the study was to assess changes in adiponectin and fibroblast growth factor 21 (FGF21) levels in pregnant women with intrahepatic cholestasis during ursodeoxycholic acid (UDCA) therapy. The study included 40 pregnant women with intrahepatic cholestasis (ICP) treated with UDCA. In the pregnant ICP group, material for further analysis was collected three times: before the first dose of drug T1, 4 weeks after the first dose of drug T2, 8 weeks after the first dose of drug T3, and 1 day after delivery T4 (P < .05). Regarding changes in the adiponectin concentration profile, three statistical significance (P < .05) was found: before the first dose and 8 weeks of treatment and 1 day after delivery, as well as between 4 and 8 weeks of UDCA acid therapy. In the fourth and eighth weeks of treatment, adiponectin levels reached a higher concentration than before the first dose of UDCA, but a decrease was observed 1 day after delivery. It has been confirmed that UDCA therapy has an impact on the dynamics of changes in adiponectin and FGF21 levels as well as indicators characterizing liver function.
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