Indirect influence of microRNA-146a on the association of IL-6 and TNF-α genetic polymorphisms with the increased risk of hip osteoarthritis.

Primary osteoarthritis (POA) is a complex hereditary disease that involves the interplay between genetics and epigenetics. MicroRNA molecules play important roles in epigenetic mechanisms. MicroRNA-146a (miR-146a) is a negative regulator of the immune response in osteoarthritis (OA). So, variations in the miR-146a gene could affect OA risk. The aim of this study was to investigate the relationships between single nucleotide polymorphisms (SNPs) in the miR-146a, interleukin-6 (IL-6), Toll-like receptor 10 (TLR10), and tumor necrosis factor-alpha (TNFA) genes and the risk for development of advanced-stage primary hip osteoarthritis (PHOA) and primary knee osteoarthritis (PKOA) in the Croatian population. A total of 609 POA patients and 656 healthy donors were genotyped for SNPs in the miR-146a (rs2910164, G>C). Since we used same patients and controls as two studies before us, we already had information about IL-6 (rs1800795, C>G), TLR10 (rs11096957, C>T), and TNFA (rs1800629, C>T) genotypes of our subjects. None of the differences were statistically significant comparing either allelic or genotypic frequencies of miR-146a SNP rs2910164 (G>C) between the PHOA and PKOA patients and controls. However, we found a significant association with risk to PHOA for the combination of genotypes (stratified miR-146a genotype with the IL-6, and stratified miR-146a genotype with the TNFA). In a multifactorial disease such as POA, we have shown the indirect relevance of a second modifying factor (miR-146a), which apparently contributes to the overall risk of PHOA. There was no risk association with the PKOA, indicating that these two localities (hip and knee) might have different risk-modifying factors.

Kinetics and Mechanism of Cyanobacteria Cell Removal Using Biowaste-Derived Activated Carbons with Assessment of Potential Human Health Impacts.

Harmful cyanobacteria blooms and the escalating impact of cyanotoxins necessitates the effective removal of cyanobacteria from water ecosystems before they release cyanotoxins. In this study, cyanobacteria removal from water samples taken from the eutrophic Aleksandrovac Lake (southern Serbia) was investigated. For that purpose, novel activated carbons derived from waste biomass-date palm leaf stalk (P_AC), black alder cone-like flowers (A_AC), and commercial activated carbon from coconut shell (C_AC) as a reference were used. To define the best adsorption conditions and explain the adsorption mechanism, the influence of contact time, reaction volume, and adsorbent mass, as well as FTIR analysis of the adsorbents before and after cyanobacteria removal, were studied. The removal efficiency of P_AC and A_AC achieved for the applied concentration of 10 mg/mL after 15 min was ~99%, while for C_AC after 24 h was only ~92% for the same concentration. To check the safety of the applied materials for human health and the environment, the concentrations of potentially toxic elements (PTEs), the health impact (HI) after water purification, and the toxicity (MTT and Comet assay) of the materials were evaluated. Although the P_AC and A_AC achieved much better removal properties in comparison with the C_AC, considering the demonstrated genotoxicity and cytotoxicity of the P_AC and the higher HI value for the C_AC, only the A_AC was further investigated. Results of the kinetics, FTIR analysis, and examination of the A_AC mass influence on removal efficiency indicated dominance of the physisorption mechanism. Initially, the findings highlighted the superior performance of A_AC, with great potential to be globally commercialized as an effective cyanobacteria cell adsorbent.

Transcriptomic Profiling for Prognostic Biomarkers in Early-Stage Squamous Cell Lung Cancer (SqCLC).

Squamous cell lung carcinoma (SqCLC) is associated with high mortality and limited treatment options. Identification of therapeutic targets and prognostic biomarkers is still lacking. This research aims to analyze the transcriptomic profile of SqCLC samples and identify the key genes associated with tumorigenesis, overall survival (OS), and a profile of the tumor-infiltrating immune cells. Differential gene expression analysis, pathway enrichment analysis, and Gene Ontology analysis on RNA-seq data obtained from FFPE tumor samples (N = 23) and healthy tissues (N = 3) were performed (experimental cohort). Validation of the results was conducted on publicly available gene expression data using TCGA LUSC (N = 225) and GTEx healthy donors' cohorts (N = 288). We identified 1133 upregulated and 644 downregulated genes, common for both cohorts. The most prominent upregulated genes were involved in cell cycle and proliferation regulation pathways (MAGEA9B, MAGED4, KRT, MMT11/13), while downregulated genes predominately belonged to immune-related pathways (DEFA1B, DEFA1, DEFA3). Results of the survival analysis, conducted on the validation cohort and commonly deregulated genes, indicated that overexpression of HOXC4 (p < 0.001), LLGL1 (p = 0.0015), and SLC4A3 (p = 0.0034) is associated with worse OS in early-stage SqCLC patients. In contrast, overexpression of GSTZ1 (p = 0.0029) and LILRA5 (p = 0.0086) was protective, i.e., associated with better OS. By applying a single-sample gene-set enrichment analysis (ssGSEA), we identified four distinct immune subtypes. Immune cell distribution suggests that the memory T cells (central and effector) and follicular helper T cells could serve as important stratification parameters.