Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used therapeutic agents that exhibit frequent and sometimes severe adverse effects, including gastrointestinal ulcerations and cardiovascular disorders. In an effort to obtain safer NSAIDs, we assessed the direct cyclooxygenase (COX) inhibition activity and we investigated the potential COX binding mode of some previously reported 2-(trimethoxyphenyl)-thiazoles. The in vitro COX inhibition assays were performed against ovine COX-1 and human recombinant COX-2. Molecular docking studies were performed to explain the possible interactions between the inhibitors and both COX isoforms binding pockets. Four of the tested compounds proved to be good inhibitors of both COX isoforms, but only compound A3 showed a good COX-2 selectivity index, similar to meloxicam. The plausible binding mode of compound A3 revealed hydrogen bond interactions with binding site key residues including Arg120, Tyr355, Ser530, Met522 and Trp387, whereas hydrophobic contacts were detected with Leu352, Val349, Leu359, Phe518, Gly526, and Ala527. Computationally predicted pharmacokinetic profile revealed A3 as lead candidate. The present data prove that the investigated compounds inhibit COX and thus confirm the previously reported in vivo anti-inflammatory screening results suggesting that A3 is a suitable candidate for further development as a NSAID.

Sortase A inhibition is a well establish strategy for decreasing bacterial virulence by affecting numerous key processes that control biofilm formation, host cell entry, evasion and suppression of the immune response and acquisition of essential nutrients. A meta-analysis of structures known to act as Sortase A inhibitors provided the starting point for identifying a new potential scaffold. Based on this template a series of new potential Sortase A inhibitors, that contain the 2-phenylthiazole moiety, were synthesized. The physicochemical characterisation confirmed the identity of the proposed structures. Antibacterial activity evaluation showed that the new compounds have a reduced activity against bacterial cell viability. However, the compounds prevent biofilm formation at very low concentrations, especially in the case of E. faecalis. Molecular docking studies performed estimate that this is most likely due to the inhibition of Sortase A. The new compounds could be used as add-on therapies together with known antibacterial agents in order to combat multidrug-resistance enterococcal infections.

Background and aims. Synthesis of new potential antimicrobial agents and evaluation of their lipophilicity.Methods. Ten new thiazolyl-oxadiazoline derivatives were synthesized and their structures were validated by 1H-NMR and mass spectrometry. The lipophilicity of the compounds was evaluated using the principal component analysis (PCA) method. The necessary data for applying this method were obtained by reverse-phase thin-layer chromatography (RP-TLC). The antimicrobial activities were tested in vitro against four bacterial strains and one fungal strain.Results. The lipophilicity varied with the structure but could not be correlated with the antimicrobial activity, since this was modest.Conclusions. We have synthesized ten new heterocyclic compounds. After their physical and chemical characterization, we determined their lipophilicity and screened their antimicrobial activity.

Introduction and Aims: Cardiovascular involvement remains one of the leading causes of morbidity and mortality in children with Chronic Kidney Disease on Renal Replacement Therapy. Left ventricular hypertrophy, aortic calcifications, arterial stiffness, hypertension and fluid overload have been recognized as important risk factors for sudden death in pediatric patients with end-stage renal disease. This study is designed to assess the relationship between the End Stage Renal Disease and Left Ventricular Mass and Diastolic Dysfunction.

Background/Objectives: Mitochondrial dysfunction and immune activation are reported across many chronic diseases, yet whether such shared signals are reproducible across independent cohorts is rarely tested. We compared the peripheral blood transcriptomes of two clinically distinct disorders, pulmonary arterial hypertension (PAH) and bipolar disorder (BD), to determine which shared transcriptomic signals remain directionally concordant across independent cohorts. Methods: Five public microarray cohorts (two PAH, three BD) were analyzed through differential expression, Hallmark gene set enrichment, and weighted gene co-expression network analysis. Instead of focusing on overlapping genes, we quantified the directional reproducibility of pathway-level signals using a stability index, evaluated against chance baselines, permutation testing, and complementary reproducibility metrics. Results: Both disorders converged on an overlapping mitochondrial–immune transcriptional program, and the interferon-α response was the only Hallmark pathway with positive normalized enrichment score (NES) values across all five cohorts and was significantly enriched in four of them. Beyond the interferon response, the broader pathway signature was directionally concordant across the two PAH cohorts (stability index = 0.66; Spearman ρ = 0.61) but not across the three BD cohorts (0.22; ρ = 0.14). Conclusions: PAH and BD share a peripheral mitochondrial–immune transcriptional program whose most reproducible element is type I interferon signaling, a signal directionally preserved across all cohorts despite differences in blood fraction. The broader transcriptomic program showed variable reproducibility that depended in part on the blood fraction sampled, highlighting the importance of evaluating both reproducibility and sample characteristics before inferring shared disease biology.