Atherosclerosis and its comorbidities are the major contributors to the global burden of death worldwide. Lower extremities arterial disease (LEAD) is a common manifestation of atherosclerotic disease of arteries of lower extremities. MicroRNAs belong to epigenetic factors that regulate gene expression and have not yet been extensively studied in LEAD. We aimed to indicate the most promising microRNA and gene expression signatures of LEAD, to identify interactions between microRNA and genes and to describe potential effect of modulated gene expression. High-throughput sequencing was employed to examine microRNAome and transcriptome of peripheral blood mononuclear cells of patients with LEAD, in relation to controls. Statistical significance of microRNAs and genes analysis results was evaluated using DESeq2 and uninformative variable elimination by partial least squares methods. Altered expression of 26 microRNAs (hsa-let-7f-1-3p, hsa-miR-34a-5p, -122-5p, -3591-3p, -34a-3p, -1261, -21-5p, -15a-5p, -548d-5p, -34b-5p, -424-3p, -548aa, -548t-3p, -4423-3p, -196a-5p, -330-3p, -766-3p, -30e-3p, -125b-5p, -1301-3p, -3184-5p, -423-3p, -339-3p, -138-5p, -99a-3p, and -6087) and 14 genes (AK5, CD248, CDS2, FAM129A, FBLN2, GGT1, NOG, NRCAM, PDE7A, RP11-545E17.3, SLC12A2, SLC16A10, SLC4A10, and ZSCAN18) were the most significantly differentially expressed in LEAD group compared to controls. Discriminative value of revealed microRNAs and genes were confirmed by receiver operating characteristic analysis. Dysregulations of 26 microRNAs and 14 genes were used to propose novel biomarkers of LEAD. Regulatory interactions between biomarker microRNAs and genes were studied in silico using R multiMiR package. Functional analysis of genes modulated by proposed biomarker microRNAs was performed using DAVID 6.8 tools and revealed terms closely related to atherosclerosis and, interestingly, the processes involving nervous system. The study provides new insight into microRNA-dependent regulatory mechanisms involved in pathology of LEAD. Proposed microRNA and gene biomarkers of LEAD may provide new diagnostic and therapeutic opportunities.

Isoquinoline alkaloids belong to the toxic secondary metabolites occurring in plants of many families. The high biological activity makes these compounds promising agents for use in medicine, particularly as anticancer drugs. The aim of our study was to evaluate the cytotoxicity and proapoptotic activity of sanguinarine, berberine, and extracts of Chelidonium majus L. and Berberis thunbergii DC. IC10, IC50, and IC90 doses were established toward hematopoietic cancer cell lines using trypan blue staining. Alterations in the expression of 18 apoptosis-related genes in cells exposed to IC10, IC50, and IC90 were evaluated using real-time PCR. Sanguinarine and Chelidonium majus L. extract exhibit significant cytotoxicity against all studied cell lines. Lower cytotoxic activity was demonstrated for berberine. Berberis thunbergii DC. extract had no influence on cell viability. Berberine, sanguinarine, and Chelidonium majus L. extract altered the expression of apoptosis-related genes in all tested cell lines, indicating the induction of apoptosis. The presented study confirmed the substantial cytotoxicity and proapoptotic activity of sanguinarine, berberine, and Chelidonium majus L. extract toward the studied hematopoietic cell lines, which indicates the utility of these substances in anticancer therapy.

Abdominal artery aneurysm (AAA) refers to abdominal aortic dilatation of 3 cm or greater. AAA is frequently underdiagnosed due to often asymptomatic character of the disease, leading to elevated mortality due to aneurysm rupture. MiRNA constitute a pool of small RNAs controlling gene expression and is involved in many pathologic conditions in human. Targeted panel detecting altered expression of miRNA and genes involved in AAA would improve early diagnosis of this disease. In the presented study, we selected and analyzed miRNA and gene expression signatures in AAA patients. Next, generation sequencing was applied to obtain miRNA and gene-wide expression profiles from peripheral blood mononuclear cells in individuals with AAA and healthy controls. Differential expression analysis was performed using DESeq2 and uninformative variable elimination by partial least squares (UVE-PLS) methods. A total of 31 miRNAs and 51 genes were selected as the most promising biomarkers of AAA. Receiver operating characteristics (ROC) analysis showed good diagnostic ability of proposed biomarkers. Genes regulated by selected miRNAs were determined in silico and associated with functional terms closely related to cardiovascular and neurological diseases. Proposed biomarkers may be used for new diagnostic and therapeutic approaches in management of AAA. The findings will also contribute to the pool of knowledge about miRNA-dependent regulatory mechanisms involved in pathology of that disease.

Chronic venous disease (CVD) is a vascular disease of lower limbs with high prevalence worldwide. Pathologic features include varicose veins, venous valves dysfunction and skin ulceration resulting from dysfunction of cell proliferation, apoptosis and angiogenesis. These processes are partly regulated by microRNA (miRNA)-dependent modulation of gene expression, pointing to miRNA as a potentially important target in diagnosis and therapy of CVD progression. The aim of the study was to analyze alterations of miRNA and gene expression in CVD, as well as to identify miRNA-mediated changes in gene expression and their potential link to CVD development. Using next generation sequencing, miRNA and gene expression profiles in peripheral blood mononuclear cells of subjects with CVD in relation to healthy controls were studied. Thirty-one miRNAs and 62 genes were recognized as potential biomarkers of CVD using DESeq2, Uninformative Variable Elimination by Partial Least Squares (UVE-PLS) and ROC (Receiver Operating Characteristics) methods. Regulatory interactions between potential biomarker miRNAs and genes were projected. Functional analysis of microRNA-regulated genes revealed terms closely related to cardiovascular diseases and risk factors. The study shed new light on miRNA-dependent regulatory mechanisms involved in the pathology of CVD. MicroRNAs and genes proposed as CVD biomarkers may be used to develop new diagnostic and therapeutic methods.

The antimicrobial properties of essential oil from Lavandula sp. raise hopes related to its use in phytotherapy. This study aimed to evaluate the antimicrobial activity of essential oils from cultivars of L. angustifolia (‘Hidcote Blue Strain’, ‘Hidcote Blue’) and L. × intermedia (‘Phenomenal’, ‘Grosso’) grown in central-eastern Poland, that is, at the border of the northern lavender cultivation range. The chemical composition of the essential oils was determined by GC/MS. Essential oil concentrations (20, 10, 5, 2.5, 1.25, 0.6, 0.3, 0.16, 0.08, and 0.04 mg/mL) were tested to determine the minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC) or minimum fungicidal concentration (MFC) towards ten strains of Gram-positive bacteria, five Gram-negative bacteria, and eight yeasts in vitro culture. Essential oils from the Lavendula cultivars showed antimicrobial activity against all microorganisms analysed. The yeasts were characterised by higher sensitivity to lavender oil compared to bacteria, while Gram-positive bacteria were more sensitive than Gram-negative bacteria. The lowest MIC values for bacteria and fungi were obtained for ‘Grosso’. Furthermore, the ‘Grosso’ oil showed the highest fungicidal activity, while the highest bactericidal activity was found in ‘Hidcote Blue’ and ‘Grosso’. Using Staphylococcus aureus as an example, it was shown that different bacterial strains of the same species show varying sensitivity to the essential oil. A higher oil content was noted for the cultivars L. × intermedia, especially for the ‘Phenomenal’. Linalyl acetate and linalool were the main components of the essential oil in all cultivars. However, in the ‘Grosso’ oil, a high content of terpinen-4-ol (18.08%) was also recorded. An analysis of the relationships between the content of the main components in the analysed essential oils and the antimicrobial activity of essential oils suggested that linalool and terpinen-4-ol were compounds potentially responsible for antimicrobial activity. The obtained results allow us to conclude that essential oil with significant antimicrobial activity can be obtained from Lavandula sp. plants harvested in the northern part of the cultivation range.