Summary: Background:The study was undertaken to assess the influence of functional -308G/A TNF-α (rs 1800629) and -174G/C IL-6 (rs1800795) promoter polymorphisms on the therapeutic response to etanercept, a TNF-α blocker, in patients with rheumatoid arthritis (RA).Methods:Seventy-three patients suffering from active RA were studied, at baseline and 6 and 12 months after therapy. The therapeutic response was estimated according to the European League Against Rheumatism response criteria. Patients were genotyped for -308G/A TNF-α and -174G/C IL-6 polymorphisms by the PCR-RFLP method, and the influence of genotype on etanercept response was assessed.Results:No difference in the percentage of responders (patients who had DAS28 improvement > 1.2) between patients with the TNF-α-308GG and GA and AA genotype was detected after 6 and 12 months of treatment. After 12 months of treatment the percentage of responders was significantly increased in patients with the IL-6 -174GG genotype compared with those with the GC or CC genotype (p=0.006 by Chi-square test). Evaluation of the patients according to their combined IL-6/TNF-α genotypes showed that patients with the IL-6 -174GG / TNF-α -308GG genotype were more frequent among the responders compared to those with other combined genotypes (p=0.022 by Chisquare test). More precisely, all patients with the combined IL-6 -174GG / TNF-α -308GG genotype were responders after 12 months of etanercept treatment.Conclusions:The study suggests that patients who are genetically low TNF-α and IL-6 producers are the best responders to etanercept therapy.

Adiponectin (ADIPOQ) as both a regulator of metabolic homeostasis and a protein involved in immune response might be of particular interest to contemporary laboratory medicine, especially in terms of minimally invasive diagnostics. The diverse roles of ADIPOQ with regard to the immune and metabolic aspects of colorectal carcinogenesis have been proposed. However, the expression of its receptors ADIPOR1 and ADIPOR2 is scarcely explored in peripheral blood mononuclear cells (PBMCs). Moreover, ADIPORs’ relationships with the immune response mediator TNF-α have not been previously investigated in the PBMCs of CRC patients. This study used both in silico and observational case–control analyses with the aim of exploring the association of ADIPOR gene expression and ADIPOQ single nucleotide polymorphisms (SNPs) with the inflammatory marker TNF-α and lipid status parameters in patients with CRC. Publicly available transcriptomic datasets (GSE47756, GSE44076) obtained from analyses of monocytes and CRC tissue samples were employed for the in silico evaluation of ADIPORs’ specific genetic traits. GSE47756 and GSE44076 datasets were processed with GSEA software to provide a genetic fingertip of different signaling pathways associated with ADIPORs’ mRNA levels. The case–control aspect of the study included the PBMC samples of 73 patients diagnosed with CRC and 80 healthy volunteers. The PCR method was carried out for the PBMC gene expression analysis (ADIPOR1, ADIPOR2, TNF-α mRNA levels) and for the subjects’ genotyping (ADIPOQ rs266729, ADIPOR1 rs7539542). GSEA showed significant associations of ADIPOR mRNA expression with gene sets related to metabolic and immune homeostasis in both datasets. The case–control study revealed the association of ADIPOR1 rs7539542 with reduced lipid status parameters in CRC. In addition, PBMC ADIPOR1 mRNA levels decreased in CRC (p < 0.001), whereas ADIPOR2 mRNA did not differ between the groups (p = 0.442). A reduction in PBMC TNF-α mRNA levels was noted in CRC (p < 0.05). Our results indicate that ADIPOR1 and ADIPOR2 play a significant role in the alteration of both metabolic and immune homeostasis during the progression of CRC. For the first time, ADIPOR1 is shown to be a specific receptor for mediating ADIPOQ’s effects in the PBMCs of CRC patients.

Antimicrobial resistance (AMR) is a global public health threat that affects cancer patients more than the general population. In this work, a composite system based on Zn-alginate hydrogel and activated charcoal (AC) particles that, upon contact with physiological fluids, simultaneously releases bioactive agents (Zn²⁺ and AC particles impregnated with povidone–iodine) was designed to locally address specific problems characteristic for malignant wounds (MWs). This composite was comprehensively investigated in vitro regarding its morphology (field-emission scanning electron microscopy), Zn²⁺ release (flame atomic absorption spectrometry), iodine adsorption and desorption from AC particles (energy dispersive X-ray analysis and UV–visible spectroscopy) as well as its antimicrobial and antitumor activity. With respect to the ongoing AMR crises, antimicrobial activity was tested against a wide range of wild multi-drug resistant bacterial and yeast strains, all isolated from patient wounds. Since Zn²⁺ ions proved to be selectors of resistant strains of bacteria, the synergistic activity of AC particles and adsorbed iodine was shown to be crucial for excellent antibacterial activity. On the other hand, the synergy of AC particles and Zn²⁺ ions showed an equally strong antifungal effect. In addition, antimicrobial concentrations of Zn²⁺ ions showed cytotoxic activity against two cancer cell lines derived from cancers affecting skin either as metastatic cancer (breast cancer MDA-MB-453 cell line) or primary cancer of the skin (malignant melanoma Fem-X cell line), which enables Zn²⁺ ions to be further investigated as potent local agents targeting malignant cells.

The aim of the study was to explore putative influence of - 308 G/A TNFα and –174 G/C IL-6 promoter polymorphisms (releated to TNFα and IL-6 level) on the therapeutic response to etanercept, a TNFα blocker, in patients with rheumathoid arthritis (RA). 73 patients suffering from active RA were examined at the begining of etanercept treatment and 6- and 12-months following the begining of the treatment. The therapeutic response was estimated according to the European League Against Rheumatism response criteria. Patients were genotyped for –308 G/A TNFα and –174 G/C IL-6 gene polymorphisms by the PCR-RFLP method, and influence of the genotype to clinical response to etanercept was assessed. Association between –308 G/A TNFα polymorphism and a response to etanercept after 6 and 12 months of therapy was not found. After 12 months the percentage of responders (patients who had DAS28 improvement > 1.2) was significantly increased in patients with the –174 GG IL-6 genotype (95.7 %) compared with those with the –174 GC IL-6 (75.6 %) and –174 CC IL-6 (44.4 %) genotype (p = 0.006). The best responders after 12 months were patients with –308 GG TNFα/–174 GG IL-6 genotype combination compared to the other genotype combinations (p = 0.022). The patients with RA exhibiting –308 GG TNFα/–174 GG IL-6 genotype respond better to etanercept than patients with other genotypes examined. This finding suggests that this polymorphism combination should be considered as a genetic marker of responsiveness to TNFα blockers in RA.