RESUMEN
Heterocyclic compounds, particularly those containing azole rings, have shown extensive biological activity, including anticancer, antibacterial, and antifungal properties. Among these, the imidazole ring stands out due to its diverse therapeutic potential. In the presented study, we designed and synthesized a series of imidazole derivatives to identify compounds with high biological potential. We focused on two groups: thiosemicarbazide derivatives and hydrazone derivatives. We synthesized these compounds using conventional methods and confirmed their structures via nuclear magnetic resonance spectroscopy (NMR), MS, and elemental analysis, and then assessed their antibacterial and antifungal activities in vitro using the broth microdilution method against Gram-positive and Gram-negative bacteria, as well as Candida spp. strains. Our results showed that thiosemicarbazide derivatives exhibited varied activity against Gram-positive bacteria, with MIC values ranging from 31.25 to 1000 µg/mL. The hydrazone derivatives, however, did not display significant antibacterial activity. These findings suggest that structural modifications can significantly influence the antimicrobial efficacy of imidazole derivatives, highlighting the potential of thiosemicarbazide derivatives as promising candidates for further development in antibacterial therapies. Additionally, the cytotoxic activity against four cancer cell lines was evaluated. Two derivatives of hydrazide-hydrazone showed moderate anticancer activity.
Asunto(s)
Antibacterianos , Antifúngicos , Antineoplásicos , Bacterias Grampositivas , Pruebas de Sensibilidad Microbiana , Humanos , Antibacterianos/farmacología , Antibacterianos/síntesis química , Antibacterianos/química , Antineoplásicos/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Antifúngicos/farmacología , Antifúngicos/síntesis química , Antifúngicos/química , Bacterias Grampositivas/efectos de los fármacos , Nitroimidazoles/farmacología , Nitroimidazoles/química , Nitroimidazoles/síntesis química , Línea Celular Tumoral , Bacterias Gramnegativas/efectos de los fármacos , Relación Estructura-Actividad , Semicarbacidas/química , Semicarbacidas/farmacología , Semicarbacidas/síntesis química , Hidrazonas/química , Hidrazonas/farmacología , Hidrazonas/síntesis química , Candida/efectos de los fármacos , Estructura MolecularRESUMEN
The genus Utricularia (bladderworts) species are carnivorous plants that prey on invertebrates using traps with a high-speed suction mechanism. The outer trap surface is lined by dome-shaped glands responsible for secreting water in active traps. In terminal cells of these glands, the outer wall is differentiated into several layers, and even cell wall ingrowths are covered by new cell wall layers. Due to changes in the cell wall, these glands are excellent models for studying the specialization of cell walls (microdomains). The main aim of this study was to check if different cell wall layers have a different composition. Antibodies against arabinogalactan proteins (AGPs) were used, including JIM8, JIM13, JIM14, MAC207, and JIM4. The localization of the examined compounds was determined using immunohistochemistry techniques and immunogold labeling. Differences in composition were found between the primary cell wall and the cell secondary wall in terminal gland cells. The outermost layer of the cell wall of the terminal cell, which was cuticularized, was devoid of AGPs (JIM8, JIM14). In contrast, the secondary cell wall in terminal cells was rich in AGPs. AGPs localized with the JIM13, JIM8, and JIM14 epitopes occurred in wall ingrowths of pedestal cells. Our research supports the hypothesis of water secretion by the external glands.
Asunto(s)
Pared Celular , Mucoproteínas , Proteínas de Plantas , Pared Celular/metabolismo , Mucoproteínas/metabolismo , Proteínas de Plantas/metabolismo , Lamiales/metabolismo , InmunohistoquímicaRESUMEN
Varicose veins (VVs) are the most common manifestation of chronic venous disease (CVD) and appear as abnormally enlarged and tortuous superficial veins. VVs result from functional abnormalities in the venous circulation of the lower extremities, such as venous hypertension, venous valve incompetence, and venous reflux. Previous studies indicate that enhanced angiogenesis and inflammation contribute to the progression and onset of VVs; however, dysregulations in signaling pathways associated with these processes in VVs patients are poorly understood. Therefore, in our study, we aimed to identify key regulators of angiogenesis and inflammation that are dysregulated in patients with VVs. Expression levels of 18 genes were analyzed in peripheral blood mononuclear cells (PBMC) using real-time PCR, as well as plasma levels of 6 proteins were investigated using ELISA. Higher levels of CCL5, PDGFA, VEGFC, TGF-alpha, TGF-beta 1, and VEGF-A, as well as lower levels of VEGFB and VEGF-C, were found to be statistically significant in the VV group compared to the control subjects without VVs. None of the analyzed factors was associated with the venous localization of the varicosities. The presented study identified dysregulations in key angiogenesis- and inflammation-related factors in PBMC and plasma from VVs patients, providing new insight into molecular mechanisms that could contribute to the development of VVs and point out promising candidates for circulatory biomarkers of this disease.
Asunto(s)
Inflamación , Leucocitos Mononucleares , Neovascularización Patológica , Várices , Humanos , Várices/metabolismo , Várices/patología , Várices/sangre , Femenino , Masculino , Persona de Mediana Edad , Neovascularización Patológica/metabolismo , Inflamación/metabolismo , Inflamación/sangre , Inflamación/patología , Leucocitos Mononucleares/metabolismo , Adulto , Anciano , Regulación de la Expresión Génica , AngiogénesisRESUMEN
Species in the genus Utricularia are carnivorous plants that prey on invertebrates using traps of leaf origin. The traps are equipped with numerous different glandular trichomes. Trichomes (quadrifids) produce digestive enzymes and absorb the products of prey digestion. The main aim of this study was to determine whether arabinogalactan proteins (AGPs) occur in the cell wall ingrowths in the quadrifid cells. Antibodies (JIM8, JIM13, JIM14, MAC207, and JIM4) that act against various groups of AGPs were used. AGP localization was determined using immunohistochemistry techniques and immunogold labeling. AGPs localized with the JIM13, JIM8, and JIM14 epitopes occurred in wall ingrowths of the pedestal cell, which may be related to the fact that AGPs regulate the formation of wall ingrowths but also, due to the patterning of the cell wall structure, affect symplastic transport. The presence of AGPs in the cell wall of terminal cells may be related to the presence of wall ingrowths, but processes also involve vesicle trafficking and membrane recycling, in which these proteins participate.
Asunto(s)
Pared Celular , Mucoproteínas , Proteínas de Plantas , Mucoproteínas/metabolismo , Proteínas de Plantas/metabolismo , Pared Celular/metabolismo , Tricomas/metabolismo , Hojas de la Planta/metabolismo , Lamiales/metabolismoRESUMEN
Various studies have shown that Hypogymnia physodes are a source of many biologically active compounds, including lichen acids. These lichen-specific compounds are characterized by antioxidant, antiproliferative, and antimicrobial properties, and they can be used in the cosmetic and pharmaceutical industries. The main aim of this study was to optimize the composition of natural deep eutectic solvents based on proline or betaine and lactic acid for the extraction of metabolites from H. physodes. The design of the experimental method and the response surface approach allowed the optimization of the extraction process of specific lichen metabolites. Based on preliminary research, a multivariate model of the experiment was developed. For optimization, the following parameters were employed in the experiment to confirm the model: a proline/lactic acid/water molar ratio of 1:2:2. Such a mixture allowed the efficient extraction of three depsidones (i.e., physodic acid, physodalic acid, 3-hydroyphysodic acid) and one depside (i.e., atranorin). The developed composition of the solvent mixtures ensured good efficiency when extracting the metabolites from the thallus of H. physodes with high antioxidant properties.
Asunto(s)
Depsidos , Lactonas , Depsidos/química , Depsidos/aislamiento & purificación , Depsidos/farmacología , Lactonas/química , Lactonas/aislamiento & purificación , Lactonas/farmacología , Disolventes Eutécticos Profundos/química , Antioxidantes/química , Antioxidantes/farmacología , Antioxidantes/aislamiento & purificación , Prolina/química , Líquenes/química , Ácido Láctico/química , Tecnología Química Verde/métodos , Betaína/química , Betaína/análogos & derivados , Betaína/farmacología , Solventes/química , Dibenzoxepinas , HidroxibenzoatosRESUMEN
BACKGROUND: Fatty acids are essential for human health. Currently, there is a search for alternative sources of fatty acids that could supplement such sources as staple crops or fishes. Turions of aquatic plants accumulate a variety of substances such as starch, free sugars, amino acids, reserve proteins and lipids. Our aim is to see if turions can be a valuable source of fatty acids. METHODS: Overwintering shoots and turions of aquatic carnivorous plants were collected. The plant material was extracted with hexane. The oils were analyzed using a gas chromatograph with mass spectrometer. RESULTS: The dominant compound in all samples was linolenic acid. The oil content was different in turions and shoots. The oil content of the shoots was higher than that of the turions, but the proportion of fatty acids in the oils from the shoots was low in contrast to the oils from the turions. The turions of Utricularia species were shown to be composed of about 50% fatty acids. CONCLUSIONS: The turions of Utricularia species can be used to obtain oil with unsaturated fatty acids. In addition, the high fatty acid content of turions may explain their ability to survive at low temperatures.
Asunto(s)
Ácidos Grasos , Brotes de la Planta , Ácidos Grasos/análisis , Brotes de la Planta/química , Cromatografía de Gases y Espectrometría de Masas , Ácido alfa-Linolénico/análisis , Aceites de Plantas/química , Aceites de Plantas/análisisRESUMEN
Over the years, several new medicinal substances have been introduced for the treatment of diseases caused by bacteria and parasites. Unfortunately, due to the production of numerous defense mechanisms by microorganisms and parasites, they still pose a serious threat to humanity around the world. Therefore, laboratories all over the world are still working on finding new, effective methods of pharmacotherapy. This research work aimed to synthesize new compounds derived from 3-trifluoromethylbenzoic acid hydrazide and to determine their biological activity. The first stage of the research was to obtain seven new compounds, including six linear compounds and one derivative of 1,2,4-triazole. The PASS software was used to estimate the potential probabilities of biological activity of the newly obtained derivatives. Next, studies were carried out to determine the nematocidal potential of the compounds with the use of nematodes of the genus Rhabditis sp. and antibacterial activity using the ACCT standard strains. To determine the lack of cytotoxicity, tests were performed on two cell lines. Additionally, an antioxidant activity test was performed due to the importance of scavenging free radicals in infections with pathogenic microorganisms. The conducted research proved the anthelmintic and antibacterial potential of the newly obtained compounds. The most effective were two compounds with a 3-chlorophenyl substituent, both linear and cyclic derivatives. They demonstrated higher efficacy than the drugs used in treatment.
Asunto(s)
Antibacterianos , Antinematodos , Semicarbacidas , Antibacterianos/farmacología , Línea Celular , HidrazinasRESUMEN
Diosmetin is a natural substance widely distributed in nature, with documented multidirectional biological effects. The wide spectrum of biological activity of diosmetin gives hope that derivatives of this flavonoid may also be used as drugs or dietary supplements used in many diseases. Modification of the structure may, on the one hand, lead to an increase in biological potency, new biological activity, or an increase in solubility and thus bioavailability. This is an important direction of research because the use of pure diosmetin is limited due to its low bioavailability. This work is an attempt to collect information on the possibility of modifying the structure of diosmetin and its impact on biological activity.
Asunto(s)
Flavonoides , Flavonoides/farmacología , Flavonoides/químicaRESUMEN
Chronic venous disease (CVD) is a condition characterized by functional disturbances in the microcirculation of the superficial and deep veins, affecting up to 30% of the global population. Diosmin, a phlebotropic drug, is commonly used in the treatment of CVD, and its beneficial effects have been described in numerous clinical studies. However, the precise molecular mechanism underlying the activity of diosmin is not yet fully understood. Therefore, the objective of our study was to investigate whether diosmin has an impact on oxygen management, as cardiovascular diseases are often associated with hypoxia. In our study, patients were administered a daily dosage of 2 × 600 mg of diosmin for 3 months, and we evaluated several factors associated with oxygen management, angiogenesis, and inflammation using biochemical assays. Our findings indicate that diosmin reduced the levels of fibroblast growth factors (FGF) and vascular endothelial growth factor (VEGF-C), while increasing endostatin and angiostatin levels, suggesting a potential influence on angiogenesis regulation. Furthermore, diosmin exhibited anti-inflammatory properties by suppressing the levels of tumor necrosis factor-alpha (TNF-α), interleukin 1-beta (IL-1ß), and interleukin 6 (IL-6), while promoting the production of interleukin 12 (IL-12). Additionally, diosmin significantly decreased the levels of hypoxia-inducible factor (HIF), anion gap (AG), and lactate, indicating its potential influence on the hypoxia-inducible factor pathway. These findings suggest that diosmin may play a crucial role in modulating oxygen management and inflammation in the context of chronic venous disease.
Asunto(s)
Enfermedades Cardiovasculares , Diosmina , Humanos , Diosmina/farmacología , Diosmina/uso terapéutico , Factor A de Crecimiento Endotelial Vascular , Interleucina-12 , Factores de Crecimiento de Fibroblastos , Hipoxia , Inflamación , Interleucina-6 , Ácido Láctico , Homeostasis , OxígenoRESUMEN
Abdominal aortic aneurysm (AAA) is a chronic vascular disease caused by localized weakening and broadening of the abdominal aorta. AAA is a clearly underdiagnosed disease and is burdened with a high mortality rate (65-85%) from AAA rupture. Studies indicate that abnormal regulation of angiogenesis and inflammation contributes to progression and onset of this disease; however, dysregulations in the molecular pathways associated with this disease are not yet fully explained. Therefore, in our study, we aimed to identify dysregulations in the key regulators of angiogenesis and inflammation in patients with AAA in peripheral blood mononuclear cells (using qPCR) and plasma samples (using ELISA). Expression levels of ANGPT1, CXCL8, PDGFA, TGFB1, VEGFB, and VEGFC and plasma levels of TGF-alpha, TGF-beta 1, VEGF-A, and VEGF-C were found to be significantly altered in the AAA group compared to the control subjects without AAA. Associations between analyzed factors and risk factors or biochemical parameters were also explored. Any of the analyzed factors was associated with the size of the aneurysm. The presented study identified dysregulations in key angiogenesis- and inflammation-related factors potentially involved in AAA formation, giving new insight into the molecular pathways involved in the development of this disease and providing candidates for biomarkers that could serve as diagnostic or therapeutic targets.
Asunto(s)
Aneurisma de la Aorta Abdominal , Leucocitos Mononucleares , Humanos , Animales , Leucocitos Mononucleares/metabolismo , Aneurisma de la Aorta Abdominal/metabolismo , Aorta Abdominal/metabolismo , Biomarcadores/metabolismo , Inflamación/metabolismo , Modelos Animales de EnfermedadRESUMEN
Since Charles Darwin and his book carnivorous plants have aroused interest and heated debate. In addition, there is growing interest in this group of plants as a source of secondary metabolites and in the application of their biological activity. The aim of this study was to trace the recent literature in search of the application of extracts obtained from families Droseraceae, Nepenthaceae, and Drosophyllaceae to show their biological potential. The data collected in the review clearly indicate that the studied Nepenthales species have great biological potential in terms of antibacterial, antifungal, antioxidant, anti-inflammatory, and anticancer use. We proposed that further investigations should include: (i) bioactivity-guided investigations of crude plant extract to connect a particular type of action with a specific compound or a group of metabolites; (ii) a search for new bioactive properties of carnivorous plants; (iii) establishment of molecular mechanisms associated with specific activity. Furthermore, further research should be extended to include less explored species, i.e., Drosophyllum lusitanicum and especially Aldrovanda vesiculosa.
Asunto(s)
Planta Carnívora , Droseraceae , Humanos , Plantas , CalorRESUMEN
Carnivorous plants are able to attract small animals or protozoa and retain them in their specialized traps. Later, the captured organisms are killed and digested. The nutrients contained in the prey bodies are absorbed by the plants to use for growth and reproduction. These plants produce many secondary metabolites involved in the carnivorous syndrome. The main purpose of this review was to provide an overview of the secondary metabolites in the family Nepenthaceae and Droseraceae, which were studied using modern identification techniques, i.e., high-performance liquid chromatography or ultra-high-performance liquid chromatography with mass spectrometry and nuclear magnetic resonance spectroscopy. After literature screening, there is no doubt that tissues of species from the genera Nepenthes, Drosera, and Dionaea are rich sources of secondary metabolites that can be used in pharmacy and for medical purposes. The main types of the identified compounds include phenolic acids and their derivatives (gallic, protocatechuic, chlorogenic, ferulic, p-coumaric acids, gallic, hydroxybenzoic, vanillic, syringic caffeic acids, and vanillin), flavonoids (myricetin, quercetin, and kaempferol derivatives), including anthocyanins (delphinidin-3-O-glucoside, cyanidin-3-O-glucoside, and cyanidin), naphthoquinones (e.g., plumbagin, droserone, and 5-O-methyl droserone), and volatile organic compounds. Due to the biological activity of most of these substances, the importance of the carnivorous plant as a pharmaceutical crop will increase.
Asunto(s)
Caryophyllales , Droseraceae , Animales , Droseraceae/química , Antocianinas , Planta Carnívora , GlucósidosRESUMEN
Phlebotropic flavonoids, including diosmin and its aglycone diosmetin, are natural polyphenols widely used in the prevention and treatment of chronic venous insufficiency (CVI). As oxidative stress plays an important role in the development of pathophysiology of the cardiovascular system, the study aimed to investigate the protective effects of diosmin and diosmetin on hydrogen peroxide (H2O2)-induced oxidative stress in endothelial cells. The cells were pretreated with different concentrations of the flavonoid prior to the H2O2 exposure. The cell viability, the level of intracellular reactive oxygen species (ROS), the activity of cellular antioxidant enzymes-including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase GPx-and the malondialdehyde (MDA) level were assessed. It was found that the H2O2-induced oxidative stress was ameliorated by diosmin/diosmetin in a concentration-dependent manner. The flavonoids restored the activity of cellular antioxidant enzymes and lowered the MDA level upregulated by the H2O2 exposure. These results indicate that diosmin and diosmetin may prevent oxidative stress in endothelial cells; therefore, they may protect against the development and progression of oxidative-stress-related disorders.
Asunto(s)
Antioxidantes , Diosmina , Antioxidantes/farmacología , Diosmina/farmacología , Peróxido de Hidrógeno/farmacología , Células Endoteliales , Estrés Oxidativo , Catalasa/farmacología , Especies Reactivas de Oxígeno/farmacología , Superóxido Dismutasa/farmacologíaRESUMEN
Diosmin is widely used as a venoactive drug in the pharmacological treatment of chronic venous disorders. It exerts a strong protective effect on blood vessels via an increase in the elasticity of vessel walls and reduces the permeability of capillary walls, thereby producing an anti-edematous effect. In this paper, we investigated the effectiveness of diosmin and diosmetin in modulating the level of proinflammatory factors in human skin fibroblasts treated with lipopolysaccharide (LPS). Two variants of the experiments were performed: the flavonoid was added 2 h prior to or 24 h after LPS stimulation. Our study revealed that both flavonoids reduced the levels of IL-6 and Il-1ß as well as COX-2 and PGE2 but had no impact on IL-10. However, the addition of the compounds prior to the LPS addition was more effective. Moreover, diosmetin modulated the proinflammatory factors more strongly than diosmin. Our investigations also showed that both flavonoids were potent inhibitors of elastase and collagenase activity, and no differences between the glycoside and aglycone forms were observed.
Asunto(s)
Diosmina , Diosmina/farmacología , Fibroblastos , Flavonoides/farmacología , Humanos , Mediadores de Inflamación , Lipopolisacáridos/farmacología , MetaloproteasasRESUMEN
A growing body of evidence indicates a crucial role of miRNA regulatory function in a variety of mechanisms that contribute to the development of diseases. In our previous work, alterations in miRNA expression levels and targeted genes were shown in peripheral blood mononuclear cells (PBMCs) from patients with lower extremity artery disease (LEAD), abdominal aortic aneurysm (AAA), and chronic venous disease (CVD) in comparison with healthy controls. In this paper, previously obtained miRNA expression profiles were compared between the LEAD, AAA, and CVD groups to find either similarities or differences within the studied diseases. Differentially expressed miRNAs were identified using the DESeq2 method implemented in the R programming software. Pairwise comparisons (LEAD vs. AAA, LEAD vs. CVD, and AAA vs. CVD) were performed and revealed 10, 8, and 17 differentially expressed miRNA transcripts, respectively. The functional analysis of the obtained miRNAs was conducted using the miRNet 2.0 online tool and disclosed associations with inflammation and cellular differentiation, motility, and death. The miRNet 2.0 tool was also used to identify regulatory interactions between dysregulated miRNAs and target genes in patients with LEAD, AAA, and CVD. The presented research provides new information about similarities and differences in the miRNA-dependent regulatory mechanisms involved in the pathogenesis of LEAD, AAA, and CVD.
RESUMEN
In the present study, the effects of foliar application of salicylic acid (100 µM), cerium oxide (50 mg L-1), and cerium oxide:salicylic acid nanoparticles (CeO2: SA-nanoparticles, 50 mg L-1 + 100 µM) on the growth and physiological responses of purslane (Portulaca oleracea L.) were examined in non-saline and saline conditions (50 and 100 mM NaCl salinity). Foliar applications mitigated salinity-induced adverse effects, and the highest plant height and N, P, Mg, and Mn content were recorded in the variant with non-saline × foliar use of CeO2: SA-nanoparticles. The highest values of fresh and dry weight were noted in the treatment with no-salinity × foliar use of CeO2:SA-nanoparticles. The highest number of sub-branches was observed in the foliar treatments with CeO2-nanoparticles and CeO2:SA-nanoparticles without salinity stress, while the lowest number was noted in the 100 mM NaCl treatment. Moreover, the foliar application of CeO2:SA-nanoparticles and cerium-oxide nanoparticles improved the total soluble solid content, K, Fe, Zn, Ca, chlorophyll a, and oil yield in the plants. The salinity of 0 and 50 mM increased the K content, 1000-seed weight, total soluble solid content, and chlorophyll b content. The use of 100 mM NaCl with no-foliar spray increased the malondialdehyde, Na, and H2O2 content and the Na+/K+ ratio. No-salinity and 50 mM NaCl × CeO2: SA-nanoparticle interactions improved the anthocyanin content in plants. The phenolic content was influenced by NaCl100 and the foliar use of CeO2:SA-nanoparticles. The study revealed that the foliar treatment with CeO2:SA-nanoparticles alleviated the side effects of salinity by improving the physiological responses and growth-related traits of purslane plants.
Asunto(s)
Cerio , Nanopartículas , Portulaca , Cerio/farmacología , Clorofila A , Peróxido de Hidrógeno , Ácido Salicílico/farmacología , Salinidad , Cloruro de Sodio/farmacologíaRESUMEN
Lower extremity artery disease (LEAD) is an underestimated chronic vascular disease caused by the formation of atherosclerotic plaques in the lower limb arteries. The pathological processes underlying this disease are regulated by many various factors, including microRNAs (miRNAs). miRNAs constitute a pool of small, non-coding RNAs with a gene expression modulatory function. In the presented study, differentially expressed miRNAs were identified in peripheral blood mononuclear cells from 18 patients with LEAD compared to 10 healthy volunteers using OpenArray RT-qPCR. Sixteen miRNAs were significantly differentially expressed in the LEAD group. Four out of them, hsa-miR-138-5p, -34a-3p, -34a-5p, and -766-3p, were consistent with a previous next-generation sequencing study. The in silico analysis performed for these four miRNAs showed associations with vascular smooth muscle cells differentiation, inflammation, and apoptosis, potentially resulting from modulation of genes involved in cell cycle, cellular adhesion, and Notch signaling. The presented study expands our knowledge on the role of miRNA in the pathology of LEAD, providing potential candidates for biomarkers of this disease.
Asunto(s)
Perfilación de la Expresión Génica , MicroARNs , Arterias/metabolismo , Biomarcadores , Perfilación de la Expresión Génica/métodos , Humanos , Leucocitos Mononucleares/metabolismo , Extremidad Inferior , MicroARNs/genéticaRESUMEN
Lower extremity artery disease (LEAD) is an underdiagnosed and globally underestimated vascular disease caused by the progressive and chronic formation of atherosclerotic plaques in the arteries of the lower limbs. Much evidence indicates that the abnormal course of pathophysiological processes underlying LEAD development is associated with altered miRNA modulatory function. In the presented study, relationships between miRNA expression and clinical indicators of this disease (ABI, claudication distance, length of arterial occlusion, Rutherford category, and plaque localization) were identified. MiRNA expression profiles were obtained using next-generation sequencing in peripheral blood mononuclear cells (PBMCs) of 40 LEAD patients. Correlation analysis performed using the Spearman rank correlation test revealed miRNAs related to ABI, claudication distance, and length of arterial occlusion. In the DESeq2 analysis, five miRNAs were found to be dysregulated in patients with Rutherford category 3 compared to patients with Rutherford category 2. No miRNAs were found to be differentially expressed between patients with different plaque localizations. Functional analysis performed using the miRNet 2.0 website tool determined associations of selected miRNAs with processes underlying vascular pathology, such as vascular smooth muscle cell differentiation, endothelial cell apoptosis, response to hypoxia, inflammation, lipid metabolism, and circadian rhythm. The most enriched functional terms for genes targeted by associated miRNAs were linked to regulation of the cell cycle, regulation of the transcription process, and nuclear cellular compartment. In conclusion, dysregulations of miRNA expression in PBMCs of patients with LEAD are indicative of the disease and could potentially be used in the prediction of LEAD progression.
RESUMEN
Vascular diseases are one of the most common causes of death and morbidity. Lower extremity artery disease (LEAD), abdominal aortic aneurysm (AAA) and chronic venous disease (CVD) belong to this group of conditions and exhibit various presentations and courses; thus, there is an urgent need for revealing new biomarkers for monitoring and potential treatment. Next-generation sequencing of mRNA allows rapid and detailed transcriptome analysis, allowing us to pinpoint the most pronounced differences between the mRNA expression profiles of vascular disease patients. Comparison of expression data of 519 DNA-repair-related genes obtained from mRNA next-generation sequencing revealed significant transcriptomic marks characterizing AAA, CVD and LEAD. Statistical, gene set enrichment analysis (GSEA), gene ontology (GO) and literature analyses were applied and highlighted many DNA repair and accompanying processes, such as cohesin functions, oxidative stress, homologous recombination, ubiquitin turnover, chromatin remodelling and DNA double-strand break repair. Surprisingly, obtained data suggest the contribution of genes engaged in the regulatory function of DNA repair as a key component that could be used to distinguish between analyzed conditions. DNA repair-related genes depicted in the presented study as dysregulated in AAA, CVD and LEAD could be utilized in the design of new biomarkers or therapies associated with these diseases.
Asunto(s)
Aneurisma de la Aorta Abdominal , Transcriptoma , Humanos , Aneurisma de la Aorta Abdominal/genética , Perfilación de la Expresión Génica , Arterias , Biomarcadores , Extremidad Inferior/irrigación sanguínea , Secuenciación de Nucleótidos de Alto Rendimiento , Daño del ADNRESUMEN
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.