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The filamentation ability of Candida albicans represents one of the main virulence factors allowing for host tissue penetration and biofilm formation. The aim of this paper was to study the genetic background of the hyperfilamentous biofilm development in vitro in C. albicans isolated from the oral cavity of a lung cancer patient. Analyzed C. albicans isolates (CA1, CA2, CA3) were chosen based on their different structures of mature biofilm. The CA3 isolate possessing hyperfilamentation properties and forming high biofilm was compared with CA1 and CA2 isolates exhibiting low or average biofilm-forming ability, respectively. The detailed biofilm organization was studied with the use of confocal scanning laser microscopy. The whole transcriptome analysis was conducted during three stages of biofilm development (24 h, 48 h, 72 h). In contrast to CA1 and/or CA2 isolate, the CA3 isolate was characterized by a significant upregulation of genes encoding for cell wall proteins (HWP1, PGA13, PGA44, ALS3) and candidalysin (ECE1), as well as being involved in iron metabolism (FRE1, ALS3), sulfur metabolism (HAL21), the degradation of aromatic compounds (HQD2), and membrane transport (DIP5, PHO89, TNA1). In contrast, some genes (SCW11, FGR41, RBE1) in the CA3 were downregulated. We also observed the overexpression of a few genes over time-mainly FRE1, ATX1, CSA2 involved in iron metabolism. This is the first insight into the potential function of multiple genes in the hyperfilamentous biofilm formation in C. albicans , primarily isolated from host tissue, which may have an important clinical impact on cancer patients. Moreover, the presented data can lay the foundation for further research on novel pathogen-specific targets for antifungal drugs.

Sixteen new Ciprofloxacin derivatives were designed and successfully synthesized. In an in silico experiment, lipophilicity was established for obtained compounds. All compounds were screened for antimicrobial activity using standard and clinical strains. As for Gram-positive hospital microorganisms, all tested derivatives were active. Measured MICs were in the range 1-16 µg/mL, confirming high antimicrobial potency. Derivative 12 demonstrated activity against all standard Gram-positive Staphylococci , within the range of 0.8-1.6 µg/mL and was confirmed as the leading structure with MICs 1 µg/mL for S. pasteuri KR 4358 and S. aureus T 5591 (clinical strains). All compounds were screened for their in vitro cytotoxic properties via the MTT method. Three of the examined compounds ( 3 , 11 and 16 ) showed good activity against cancer cells, and in parallel were found not to be cytotoxic toward normal cells. Doxorubicin SI ranged 0.14-1.11 while the mentioned three ranged 1.9-3.4. Selected Ciprofloxacin derivatives were docked into the crystal structure of topoisomerase II (DNA gyrase) in complex with DNA (PDB ID: 5BTC). In summary, leading structures were established ( 3 , 11 , 12 and 16 ). We have observed poor results in preformed studies for disubstituted derivatives, suggesting that 3-oxo-4-carboxylic acid core is the active DNA-gyrase binding site, and when structural changes were made in this fragment, there was an observed decrease in antibacterial potency.

Eleven novel imide-tetrazoles were synthesized. In the initial stage of research, in silico structure-based pharmacological prediction was conducted. All compounds were screened for antimicrobial activity using standard and clinical strains. Within the studied group, compounds 1 - 3 were recognized as leading structures with the most promising results in antimicrobial studies. Minimal inhibitory concentration values for compounds 1 , 2 , 3 were within the range of 0.8-3.2 μg/mL for standard and clinical Gram-positive and Gram-negative bacterial strains, showing in some cases higher activity than the reference Ciprofloxacin. Additionally, all three inhibited the growth of all clinical Staphylococci panels: Staphylococcus aureus (T5592; T5591) and Staphylococcus epidermidis (5253; 4243) with MIC values of 0.8 μg/mL. Selected compounds were examined in topoisomerase IV decatenation assay and DNA gyrase supercoiling assay, followed by suitable molecular docking studies to explore the possible binding modes. In summary, the presented transition from substrate imide-thioureas to imide-tetrazole derivatives resulted in significant increase of antimicrobial properties. The compounds 1 - 3 proposed here provide a promising basis for further exploration towards novel antimicrobial drug candidates.

Several human tissues are investigated in studies of molecular biomarkers associated with diseases development. Special attention is focused on the blood and its components due to combining abundant information about systemic responses to pathological processes as well as high accessibility. In the current study, transcriptome profiles of peripheral blood mononuclear cells (PBMCs) were used to compare differentially expressed genes between patients with lower extremities arterial disease (LEAD), abdominal aortic aneurysm (AAA) and chronic venous disease (CVD). Gene expression patterns were generated using the Ion S5XL next-generation sequencing platform and were analyzed using DESeq2 and UVE-PLS methods implemented in R programming software. In direct pairwise analysis, 21, 58 and 10 differentially expressed genes were selected from the comparison of LEAD vs. AAA, LEAD vs. CVD and AAA vs. CVD patient groups, respectively. Relationships between expression of dysregulated genes and age, body mass index, creatinine levels, hypertension and medication were identified using Spearman rank correlation test and two-sided Mann-Whitney U test. The functional analysis, performed using DAVID website tool, provides potential implications of selected genes in pathological processes underlying diseases studied. Presented research provides new insight into differences of pathogenesis in LEAD, AAA and CVD, and selected genes could be considered as potential candidates for biomarkers useful in diagnosis and differentiation of studied diseases.

External apical root resorption (EARR) is one of the most serious complications associated with orthodontic treatment. The aim of the study was to analyze the relationships between selected single nucleotide polymorphisms (SNPs) in Interleukin 1 receptor antagonist ( IL1RN ), purinoreceptor P2X7 ( P2RX7 ) and EARR in patients after orthodontic treatment. The study comprised 101 patients who underwent a complex orthodontic treatment with a combination of fixed appliances. Roots were measured based on orthopantomograms and lateral cephalometric radiographs taken before and at the end of the treatment using diagnostic software. Proportional measurements of selected teeth were made using the modified Linge and Linge methods. Based on the presence or absence of EARR, patients were divided into two groups: control group, 61 patients without EARR (with 0.90 ≤ rRCR ≤ 1.00), and EARR group, 40 patients with EARR (rRCR < 0.90). Root resorption in selected groups was also evaluated with the scores of Malmgren and Levander. SNP analysis was performed using the real-time polymerase chain reaction (PCR) method. The analysis indicated that a specific haplotype of P2RX7 (rs208294) and IL1RN (rs419598) modified the risk of EARR development ( p < 0.05), with a Bonferroni correction. The analysis of the P2RX7 and IL1RN gene polymorphisms showed that the presence of SNPs of these genes may predispose individuals to EARR. These findings indicate that EARR is a complex condition influenced not only by environmental factors and needs further study on the genetic risk factors.