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1.
Int J Mol Sci ; 24(17)2023 Aug 24.
Artículo en Inglés | MEDLINE | ID: mdl-37685975

RESUMEN

Reactive α-dicarbonyls (α-DCs), such as methylglyoxal (MGO), glyoxal (GO), and 3-deoxyglucosone (3-DG), are potent precursors in the formation of advanced glycation end products (AGEs). In particular, MGO and MGO-derived AGEs are thought to be involved in the development of vascular complications in diabetes. Experimental studies showed that citrus and pomegranate polyphenols can scavenge α-DCs. Therefore, the aim of this study was to evaluate the effect of a citrus and pomegranate complex (CPC) on the α-DCs plasma levels in a double-blind, placebo-controlled cross-over trial, where thirty-six elderly subjects were enrolled. They received either 500 mg of Citrus sinensis peel extract and 200 mg of Punica granatum concentrate in CPC capsules or placebo capsules for 4 weeks, with a 4-week washout period in between. For the determination of α-DCs concentrations, liquid chromatography tandem mass spectrometry was used. Following four weeks of CPC supplementation, plasma levels of MGO decreased by 9.8% (-18.7 nmol/L; 95% CI: -36.7, -0.7 nmol/L; p = 0.042). Our findings suggest that CPC supplementation may represent a promising strategy for mitigating the conditions associated with MGO involvement. This study was registered on clinicaltrials.gov as NCT03781999.


Asunto(s)
Citrus , Granada (Fruta) , Anciano , Humanos , Cápsulas , Productos Finales de Glicación Avanzada , Óxido de Magnesio , Piruvaldehído
2.
Molecules ; 28(6)2023 Mar 22.
Artículo en Inglés | MEDLINE | ID: mdl-36985839

RESUMEN

The most significant reactive α-dicarbonyl RCS involved in the pathomechanism of glycation and related diseases is methylglyoxal (MGO). Hyperglycemia promotes the generation of MGO and leads to the formation of advanced glycation end products (AGEs). Therefore, MGO trapping and glycation inhibition appear to be important therapeutic targets in prediabetes, diabetes, and in the early prevention of hyperglycemic complications. Peppermint leaf is commonly used as herbal tea, rich in polyphenols. Eriocitrin, its predominant component, in a double-blind, randomized controlled study reversed the prediabetic condition in patients. However, the antiglycation activity of this plant material and its polyphenols has not been characterized to date. Therefore, the aim of this study was to evaluate the ability of a peppermint leaf dry extract and its polyphenols to inhibit non-enzymatic protein glycation in a model with bovine serum albumin (BSA) and MGO as a glycation agent. Peppermint polyphenols were also evaluated for their potential to trap MGO in vitro, and the resulting adducts were analyzed by UHPLC-ESI-MS. To relate chemical composition to glycation inhibitory activity, the obtained peppermint extract was subjected to qualitative and quantitative analysis. The capability of peppermint leaf polyphenols to inhibit glycation (27.3-77.2%) and form adducts with MGO was confirmed. In the case of flavone aglycones, mono- and di-adducts with MGO were observed, while eriodictyol and eriocitrin effectively produced only mono-adducts. Rosmarinic acid and luteolin-7-O-glycosides did not reveal this action. IC50 of the peppermint leaf dry extract was calculated at 2 mg/mL, equivalent to a concentration of 1.8 µM/mL of polyphenols, including ~1.4 µM/mL of flavonoids and ~0.4 µM/mL of phenolic acids. The contribution of the four major components to the anti-AGE activity of the extract was estimated at 86%, including eriocitrin 35.4%, rosmarinic acid 25.6%, luteolin-7-O-rutinoside 16.9%, luteolin-7-O-ß-glucuronoside 8.1%, and others 14%. The effect of peppermint dry extract and polyphenols in inhibiting MGO-induced glycation in vitro was comparable to that of metformin used as a positive control.


Asunto(s)
Polifenoles , Piruvaldehído , Humanos , Polifenoles/química , Piruvaldehído/química , Mentha piperita/química , Luteolina/análisis , Óxido de Magnesio , Extractos Vegetales/química , Hojas de la Planta/química , Productos Finales de Glicación Avanzada/química , Ácido Rosmarínico
3.
Int J Mol Sci ; 23(23)2022 Nov 25.
Artículo en Inglés | MEDLINE | ID: mdl-36499065

RESUMEN

The excessive dietary intake of simple sugars and abnormal metabolism in certain diseases contribute to the increased production of α-dicarbonyls (α-DCs), such as methylglyoxal (MGO) and glyoxal (GO), the main precursors of the formation of advanced glycation end products (AGEs). AGEs play a vital role, for example, in the development of cardiovascular diseases and diabetes. Aspalathus linearis (Burman f.) R. Dahlgren (known as rooibos tea) exhibits a wide range of activities beneficial for cardio-metabolic health. Thus, the present study aims to investigate unfermented and fermented rooibos extracts and their constituents for the ability to trap MGO and GO. The individual compounds identified in extracts were tested for the capability to inhibit AGEs (with MGO or GO as a glycation agent). Ultra-high-performance liquid chromatography coupled with an electrospray ionization mass spectrometer (UHPLC-ESI-MS) was used to investigate α-DCs' trapping capacities. To evaluate the antiglycation activity, fluorescence measurement was used. The extract from the unfermented rooibos showed a higher ability to capture MGO/GO and inhibit AGE formation than did the extract from fermented rooibos, and this effect was attributed to a higher content of dihydrochalcones. The compounds detected in the extracts, such as aspalathin, nothofagin, vitexin, isovitexin, and eriodictyol, as well as structurally related phloretin and phloroglucinol (formed by the biotransformation of certain flavonoids), trapped MGO, and some also trapped GO. AGE formation was inhibited the most by isovitexin. However, it was the high content of aspalathin and its higher efficiency than that of metformin that determined the antiglycation and trapping properties of green rooibos. Therefore, A. linearis, in addition to other health benefits, could potentially be used as an α-DC trapping agent and AGE inhibitor.


Asunto(s)
Aspalathus , Aspalathus/química , Flavonoides/química , Extractos Vegetales/farmacología , Extractos Vegetales/química , Productos Finales de Glicación Avanzada
4.
Molecules ; 27(16)2022 Aug 19.
Artículo en Inglés | MEDLINE | ID: mdl-36014531

RESUMEN

Strawberry leaves are considered a valuable waste material; so far, mainly due to their antioxidant properties. Since the annual production of this crop is high, our study aimed to thoroughly examine the chemical composition and antidiabetes-related bioactivity of Fragaria × ananassa leaf of its popular and productive cultivar Senga Sengana. Leaves from three different seasons, collected after fruiting, were extensively analyzed (UHPLC-qTOF-MS/MS, HPLC-DAD). Some individual components were isolated and quantified, including specific flavonol diglycosides (e.g., 3-O-[ß-xylosyl(1‴→2″)]-ß-glucuronosides). The separated quercetin glycosides were tested in an antiglycation assay, and their methylglyoxal uptake capacity was measured. In addition, the biodegradable polyester precursor 2-pyrone-4,6-dicarboxylic acid (PDC) was confirmed at relatively high levels, providing further opportunity for strawberry leaf utilization. We want to bring to the attention of the food, pharmaceutical, and cosmetic industries the Senga Sengana strawberry leaf as a new botanical raw material. It is rich in PDC, ellagitannins, and flavonols-potent glycation inhibitors.


Asunto(s)
Fragaria , Flavonoles/análisis , Fragaria/química , Frutas/química , Taninos Hidrolizables/análisis , Hojas de la Planta/química , Pironas , Espectrometría de Masas en Tándem
5.
Molecules ; 27(8)2022 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-35458630

RESUMEN

Reactive oxygen and carbonyl species promote oxidative and carbonyl stress, and the development of diabetes, metabolic syndrome, cardiovascular diseases, and others. The traditional herb Cistus × incanus is known for its antioxidant properties; therefore, the current study aimed to assess how the chemical composition of a C. incanus water infusion corresponds with its antioxidative and antiglycative effects in vitro. The composition of infusions prepared from commercial products was analyzed with UHPLC-ESI-qTOF-MS. Total phenolics, flavonoids, and non-flavonoid polyphenols were determined. Antioxidant activity of infusions and selected polyphenols was investigated using DPPH, ABTS, and FRAP. Fluorometric measurements and methylglyoxal capture were performed to investigate the antiglycation activity. PCA and PLS-DA models were applied to explore the correlation between chemical and antioxidant results. The principal flavonoids in C. incanus were flavonols. In vitro tests revealed that a stronger antioxidant effect was demonstrated by plant material from Turkey rich in flavonoids, followed by Albania and Greece. Flavonols and ellagic acid displayed stronger antiradical and reducing power than EA-derived urolithins. Hyperoside was the most potent inhibitor of glycation. The results indicate that flavonoids are primarily responsible for rock rose antioxidant and antiglycation properties. PLS-DA modeling can be used to identify the origin of plant material with sensitivity and specificity exceeding 86%.


Asunto(s)
Cistus , Antioxidantes/química , Antioxidantes/farmacología , Cistus/química , Flavonoides/química , Flavonoides/farmacología , Flavonoles , Fenoles/química , Fenoles/farmacología , Extractos Vegetales/química , Extractos Vegetales/farmacología , Polifenoles/química , Polifenoles/farmacología , Agua
6.
Int J Mol Sci ; 22(18)2021 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-34576189

RESUMEN

Reactive carbonyl species (RCS) such as methylglyoxal (MGO) or glyoxal (GO) are the main precursors of the formation of advanced glycation end products (AGEs). AGEs are a major factor in the development of vascular complications in diabetes. Vasoprotectives (VPs) exhibit a wide range of activities beneficial to cardiovascular health. The present study aimed to investigate selected VPs and their structural analogs for their ability to trap MGO/GO, inhibit AGE formation, and evaluate their antioxidant potential. Ultra-high-performance liquid chromatography coupled with an electrospray ionization mass spectrometer (UHPLC-ESI-MS) and diode-array detector (UHPLC-DAD) was used to investigate direct trapping capacity and kinetics of quenching MGO/GO, respectively. Fluorimetric and colorimetric measurements were used to evaluate antiglycation and antioxidant action. All tested substances showed antiglycative effects, but hesperetin was the most effective in RCS scavenging. We demonstrated that rutin, diosmetin, hesperidin, and hesperetin could trap both MGO and GO by forming adducts, whose structures we proposed. MGO-derived AGE formation was inhibited the most by hesperetin, and GO-derived AGEs by diosmetin. High reducing and antiradical activity was confirmed for quercetin, rutin, hesperetin, and calcium dobesilate. Therefore, in addition to other therapeutic applications, some VPs could be potential candidates as antiglycative agents to prevent AGE-related complications of diabetes.


Asunto(s)
Productos Finales de Glicación Avanzada/metabolismo , Animales , Antioxidantes/metabolismo , Cromatografía Líquida de Alta Presión , Hesperidina/farmacología , Humanos , Concentración de Iones de Hidrógeno , Piruvaldehído/farmacología , Espectrometría de Masa por Ionización de Electrospray
7.
Molecules ; 25(24)2020 Dec 09.
Artículo en Inglés | MEDLINE | ID: mdl-33317096

RESUMEN

Galega officinalis L. has been known for centuries as an herbal medicine used to alleviate the symptoms of diabetes, but its comprehensive chemical composition and pharmacological activity are still insufficiently known. The current study involved the qualitative and quantitative phytochemical analysis and in vitro evaluation of the antioxidative and methylglyoxal (MGO) trapping properties of galega herb. Ultra high-performance liquid chromatography coupled with both the electrospray ionization mass spectrometer and diode-array detector (UHPLC-ESI-MS and UHPLC-DAD) were used to investigate the composition and evaluate the anti-MGO capability of extracts and their components. Hot water and aqueous methanol extracts, as well as individual compounds representing phytochemical groups, were also assessed for antioxidant activity using DPPH (2,2-diphenyl-1-(2,4,6-trinitrophenyl)hydrazyl) and ABTS (2,2'-azino-bis(3-ethylbenz-thiazoline-6-sulfonic acid) assays. Quercetin and metformin were used as a positive control. We confirmed the presence of tricyclic quinazoline alkaloids, guanidines, flavonoids, and hydroxycinnamic acids (HCAs) in galega extracts. The polyphenolic fraction was dominated by mono-, di-, and triglycosylated flavonols, as well as monocaffeoylhexaric acids. The in vitro tests indicated which G. officinalis components exhibit beneficial antioxidative and MGO trapping effects. For galega extracts, flavonols, and HCAs, a potent antiradical activity was observed. The ability to trap MGO was noted for guanidines and flavonoids, whereas HCA esters and quinazoline alkaloids were ineffective. The formation of mono-MGO adducts of galegine, hydroxygalegine, and rutin in the examined water infusion was observed.


Asunto(s)
Antioxidantes/química , Galega/química , Fitoquímicos/química , Alcaloides/química , Antioxidantes/farmacología , Cromatografía Líquida de Alta Presión , Flavonoides/química , Guanidinas/química , Hidroxibenzoatos/química , Técnicas In Vitro , Medicina Tradicional , Estructura Molecular , Fitoquímicos/farmacología , Extractos Vegetales/química , Extractos Vegetales/farmacología , Preparaciones de Plantas/química , Preparaciones de Plantas/farmacología , Plantas Medicinales/química , Polifenoles/química , Piruvaldehído/análogos & derivados , Piruvaldehído/química , Quinazolinas/química , Espectrometría de Masa por Ionización de Electrospray
8.
J Exp Bot ; 70(18): 4689-4704, 2019 09 24.
Artículo en Inglés | MEDLINE | ID: mdl-31087066

RESUMEN

The chloroplast thylakoid network is a dynamic structure which, through possible rearrangements, plays a crucial role in regulation of photosynthesis. Although the importance of the main components of the thylakoid membrane matrix, galactolipids, in the formation of the network of internal plastid membrane was found before, the structural role of monogalactosyldiacylglycerol (MGDG) and digalactosylidacylglycerol (DGDG) is still largely unknown. We elucidated detailed structural modifications of the thylakoid membrane system in Arabidopsis thaliana MGDG- and DGDG-deficient mutants. An altered MGDG/DGDG ratio was structurally reflected by formation of smaller grana, local changes in grana stacking repeat distance, and significant changes in the spatial organization of the thylakoid network compared with wild-type plants. The decrease of the MGDG level impaired the formation of the typical helical grana structure and resulted in a 'helical-dichotomic' arrangement. DGDG deficiency did not affect spatial grana organization but changed the shape of the thylakoid membrane network in situ from lens like into a flattened shape. Such structural disturbances were accompanied by altered composition of carotenoid and chlorophyll-protein complexes, which eventually led to the decreased photosynthetic efficiency of MGDG- and DGDG-deficient plants.


Asunto(s)
Arabidopsis/metabolismo , Galactolípidos/deficiencia , Tilacoides/metabolismo , Cloroplastos/metabolismo
9.
Molecules ; 23(8)2018 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-30044380

RESUMEN

Adenosine receptors are involved in many physiological processes and pathological conditions and are therefore attractive therapeutic targets. To identify new types of effective ligands for these receptors, a library of adenosine derivatives bearing a boron cluster or phenyl group in the same position was designed. The ligands were screened in silico to determine their calculated affinities for the A2A and A3 adenosine receptors. An virtual screening protocol based on the PatchDock web server was developed. In the first screening phase, the effects of the functional group (organic or inorganic modulator) on the adenosine ligand affinity for the receptors were determined. Then, the lead compounds were identified for each receptor in the second virtual screening phase. Two pairs of the most promising ligands, compounds 3 and 4, and two ligands with lower affinity scores (compounds 11 and 12, one with a boron cluster and one with a phenyl group) were synthesized and tested in a radioligand replacement assay for affinity to the A2A and A3 receptors. A reasonable correlation of in silico and biological assay results was observed. In addition, the effects of a phenyl group and boron cluster, which is new adenosine modifiers, on the adenosine ligand binding were compared.


Asunto(s)
Adenosina/análogos & derivados , Adenosina/química , Boranos/química , Receptor de Adenosina A3/química , Receptores de Adenosina A2/química , Adenosina/farmacología , Sitios de Unión , Boranos/farmacología , Simulación por Computador , Células HeLa , Humanos , Ligandos , Simulación del Acoplamiento Molecular , Estructura Molecular , Unión Proteica , Conformación Proteica , Ensayo de Unión Radioligante , Receptor de Adenosina A3/metabolismo , Receptores de Adenosina A2/metabolismo , Relación Estructura-Actividad
10.
Platelets ; 27(5): 433-9, 2016 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-26836594

RESUMEN

Recently, polyphenols have gained attention as potential natural cardioprotective therapeutics, due to their antiplatelet, anti-inflammatory and anticoagulant activity. Species belonging to the genus Rubus sp. have been reported to be a source of polyphenolic compounds with antioxidative proprieties and beneficial biological activities. This study investigates the effects of leaf extracts obtained from red raspberry (Rubus idaeus L.) and European dewberry (Rubus caesius L.) on the reactivity of blood platelets. In ADP-stimulated blood, raspberry and dewberry extracts (15 µg/ml) markedly decreased platelet surface membrane expression of activated GPIIbIIIa receptor by 16% and 21%, respectively (P < 0.01) and significantly inhibited platelet aggregation (by 31-41% for raspberry and by 38-55% for dewberry, P < 0.01). In platelet-rich plasma (PRP), the extracts had no effect on ADP-induced platelet aggregation. The effectiveness of the extracts in whole blood and the lack of their activity in PRP indicate that leukocytes are likely to participate in the platelet response to the extracts. Our experiments show that the extracts significantly reduced the amount of free radicals released by activated neutrophils in whole blood (P < 0.001), as well as in suspensions of isolated neutrophils (P < 0.05). Moreover, the reduced number of neutrophils leads to the decreased efficiency of the extracts in the inhibition of platelet aggregation. In summary, our findings show that the raspberry and dewberry leaf extracts considerably modulated blood platelet reactivity in whole blood: they influenced blood platelet aggregation, possibly via the modulation of the redox status dependent on the oxidative activity of neutrophils.


Asunto(s)
Plaquetas/efectos de los fármacos , Plaquetas/metabolismo , Extractos Vegetales/farmacología , Agregación Plaquetaria/efectos de los fármacos , Rubus/química , Antioxidantes/metabolismo , Biomarcadores , Comunicación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Humanos , Recuento de Leucocitos , Neutrófilos/efectos de los fármacos , Neutrófilos/inmunología , Neutrófilos/metabolismo , Fosforilación , Activación Plaquetaria/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Estallido Respiratorio/efectos de los fármacos , Estallido Respiratorio/inmunología
11.
Anticancer Drugs ; 25(10): 1141-51, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-25035962

RESUMEN

The most important factors involved in tumor metastasis and angiogenesis are metalloproteinases (MMPs), vascular endothelial growth factor, and multifunctional transforming growth factor ß1. These factors are responsible for extracellular matrix degradation, induction of vascular permeability, and enhancement of tumor cells' invasion and metastasis. Elevated expression and secretion of the above-mentioned factors are correlated with the higher aggressiveness of tumors and low patient survival for example, patients with ovarian cancer. Therefore, regulation of the expression, secretion, and activity of these factors is still considered a potent target for therapeutic intervention in cancer patients. Nitric oxide (NO) donors belong to the class of agents with multivalent targeted activities in cancer cells and are considered potential anticancer therapeutics. Our studies have shown that NO donors such as spermine/NO and diethylenetriamine/NO decrease the secretion of vascular endothelial growth factor-A from the OVCAR-3 ovarian cancer cell line, but not from the SK-OV-3 ovarian cancer cell line. The release of MMP-2 from both cell lines was reduced in a soluble guanylate cyclase-dependent manner by spermine/NO and diethylenetriamine/NO. Nevertheless, MMP-2 activity was only affected in SK-OV-3 cells. Both NO donors reduced the transmigration of the ovarian cancer cell lines. We did not observe any significant effect of spermine/NO and diethylenetriamine/NO on mRNA expression of the tested aggressiveness factors. In conclusion, our data indicated that NO donors reduced the metastatic potential of ovarian cancer cells, but its impact is rather low and requires high concentrations of donors. Moreover, both the tested cell lines differed in the susceptibility to NO donors.


Asunto(s)
Antineoplásicos/farmacología , Donantes de Óxido Nítrico/farmacología , Compuestos Nitrosos/farmacología , Neoplasias Ováricas/patología , Espermina/análogos & derivados , Línea Celular Tumoral/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Femenino , Humanos , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Invasividad Neoplásica , Espermina/farmacología , Factor de Crecimiento Transformador beta1/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo
12.
Bioorg Med Chem Lett ; 24(14): 3073-8, 2014 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-24881569

RESUMEN

An impact of adenosine modification with electroneutral, lipophilic 1,12-dicarba-closo-dodecaborane or electronegative 7,8-dicarba-nido-undecaborane boron cluster at the 6-N, 2'-C and 2-C positions on human neutrophil oxidative burst, neutrophil adherence to fibronectin and protein kinase C activity was studied. Modification of adenosine with 1,12-dicarba-closo-dodecaborane, but not 7,8-dicarba-nido-undecaborane, changes the function of adenosine from an inactive to an active state in regulating neutrophil response to PMA stimulation by reducing neutrophils' reactivity through a mechanism involving the PKC signaling pathway. Our results show that exogenously administered adenosine derivatives can be useful in regulating the oxidative burst of neutrophils in the inflammatory process.


Asunto(s)
Adenosina/análogos & derivados , Adenosina/farmacología , Boratos/química , Compuestos de Boro/química , Neutrófilos/efectos de los fármacos , Adenosina/química , Relación Dosis-Respuesta a Droga , Humanos , Estructura Molecular , Neutrófilos/metabolismo , Relación Estructura-Actividad
13.
Mediators Inflamm ; 2014: 498395, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25120288

RESUMEN

Cholesterol oxidase (ChoD) is considered to be an important virulence factor for Mycobacterium tuberculosis (Mtb), but its influence on macrophage activity is unknown. Here we used Nocardia erythropolis ChoD, which is very similar to the Mtb enzyme (70% identity at the amino-acid level), to evaluate the impact of bacterial ChoD on the activity of THP-1-derived macrophages in vitro. We found that ChoD decreased the surface expression of Toll-like receptor type 2 (TLR2) and complement receptor 3 (CR3) on these macrophages. Flow cytometry and confocal microscopy showed that ChoD competed with lipoteichoic acid for ligand binding sites on TLR2 but not on CR3, suggesting that ChoD signaling is mediated via TLR2. Binding of ChoD to the membrane of macrophages had diverse effects on the activity of macrophages, activating p38 mitogen activated kinase and stimulating production of a large amount of interleukin-10. Moreover, ChoD primed macrophages to enhance the production of reactive oxygen species in response to the phorbol myristate acetate, which was reduced by "switching off" TLR-derived signaling through interleukin-1 receptor-associated kinases 1 and 4 inhibition. Our study revealed that ChoD interacts directly with macrophages via TLR2 and influences the biological activity of macrophages during the development of the initial response to infection.


Asunto(s)
Colesterol Oxidasa/metabolismo , Macrófagos/metabolismo , Receptor Toll-Like 2/metabolismo , Línea Celular , Supervivencia Celular/fisiología , Humanos , Interleucina-10/metabolismo , Unión Proteica , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/fisiología
14.
Biomedicines ; 11(11)2023 Nov 03.
Artículo en Inglés | MEDLINE | ID: mdl-38001968

RESUMEN

BACKGROUND: The abnormal serum concentration of methylglyoxal (MGO) has been presented as an indicator of chronic complications in diabetes (DM). Because such complications are also found in pre-DM, we decided to assess the concentration of this compound in individuals with pre-DM, without cardio-vascular diseases. METHODS: Frozen samples from individuals newly diagnosed with pre-DM (N = 31) and healthy subjects (N = 11) were prepared and MGO concentration was determined using UHPLC-ESI-QqTOF-MS. RESULTS: Statistical significance was established when the groups were compared for body weight, BMI, fasting glucose level, fatty liver and use of statins but not for the other descriptive parameters. The positive linear correlation showed that the higher HbA1c, the higher MGO concentration (p = 0.01). The values of MGO were within the normal range in both groups (mean value for pre-DM: 135.44 nM (±SD = 32.67) and for the control group: 143.25 nM (±SD = 17.93); p = 0.46 (±95% CI)), with no statistical significance between the groups. CONCLUSIONS: We did not confirm the elevated MGO levels in the group of patients with pre-DM. The available data suggests a possible effect of statin intake on MGO levels. This thesis requires confirmation on a larger number of patients with an assessment of MGO levels before and after the introduction of statins.

15.
Inflamm Res ; 61(1): 11-6, 2012 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-21960458

RESUMEN

OBJECTIVE AND DESIGN: We present a retrospective analysis of previously collected blood samples to determine whether the immune response of neutrophils depends on the season i.e., short versus long days, in which blood samples were collected. METHODS: The bactericidal activity and adhesive capacity of neutrophils, the production of reactive oxygen species (ROS), and CD11b/CD18 molecule expression level were investigated. The investigated neutrophils were divided into two groups based on the time of blood collection: the winter season with short days and the summer season with long days. RESULTS: We found seasonal variation in measurements of all the analyzed functional responses of neutrophils to stimuli. The strongest adhesion, as well as maximum values of ROS production, was presented by neutrophils isolated from the summer group. The highest bactericidal activity of neutrophils was also observed in blood donors from summer group. CONCLUSIONS: The magnitude of the immune functional activity of neutrophils varies with the season of the year and is decreased in winter.


Asunto(s)
Neutrófilos/citología , Estaciones del Año , Antiinfecciosos/farmacología , Antígeno CD11b/biosíntesis , Antígenos CD18/biosíntesis , Adhesión Celular , Colorantes/farmacología , Escherichia coli/metabolismo , Humanos , Sistema Inmunológico , Masculino , Neutrófilos/metabolismo , Neutrófilos/fisiología , Especies Reactivas de Oxígeno , Estudios Retrospectivos , Sales de Tetrazolio/farmacología , Tiazoles/farmacología , Factores de Tiempo
16.
Immunol Invest ; 41(4): 382-98, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22221142

RESUMEN

Several groups of author have published that, in most cases of carcinoma, circulating lymphocytes are unable to carry out immune functions successfully. A molecular mechanism responsible for T lymphocytes defective reactivity in cancer patients is not completely defined. We evaluated whether the impaired function of peripheral blood lymphocytes (PBLs) from ovarian cancer patients could be associated with signaling elements such as JAK3, STAT3 and CD3-zeta chain. The study addressed to the simultaneous expression and phosphorylation status of mentioned molecules evaluation in regard to lymphocyte function in patients with advanced ovarian cancer has not yet been demonstrated by others. We found that PBLs of cancer patients showed lower JAK3, CD3-zeta molecules expression levels, as well as lower STAT3 and CD3-zeta phosphorylation levels than cells of control. The lower proliferative response and IL-2 production capacity of cancer patients PBLs in comparison with that of the control group cells were the functional consequences of reported in this study signaling abnormalities.


Asunto(s)
Complejo CD3/metabolismo , Janus Quinasa 3/metabolismo , Linfocitos/metabolismo , Neoplasias Ováricas/inmunología , Neoplasias Ováricas/metabolismo , Factor de Transcripción STAT3/metabolismo , Transducción de Señal , Adulto , Anciano , Femenino , Humanos , Linfocitos/inmunología , Persona de Mediana Edad , Fosforilación
17.
Bioorg Med Chem ; 20(22): 6621-9, 2012 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-23063523

RESUMEN

Methods for the synthesis of adenosine/boron cluster conjugates are proposed and the potential of the obtained derivatives to modulate neutrophil activity, especially reactive oxygen species (ROS) production in vitro, is described. An efficient inhibition of ROS production in activated neutrophils by adenosine modified at the 2'-C and 6-N positions with a para-carborane cluster (C(2)B(10)H(11)) was discovered. The high affinity of the selected compounds for adenosine receptor A(2A) was established. These results are in agreement with the possible involvement of receptor A(2A) in the biological activities of adenosine/boron cluster conjugates. This study extends the range of innovative molecules available for testing as agents affecting inflammatory processes.


Asunto(s)
Adenosina/análogos & derivados , Boro/química , Neutrófilos/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Adenosina/síntesis química , Adenosina/farmacología , Supervivencia Celular/efectos de los fármacos , Humanos , Neutrófilos/citología , Receptor de Adenosina A2A/química , Receptor de Adenosina A2A/metabolismo
18.
Res Microbiol ; 170(2): 80-85, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-30521846

RESUMEN

Infectious urolithiasis is a consequence of long-standing urinary tract infections with urease-positive bacteria, especially Proteus spp. However, because of the often mixed nature of urinary tract infections, in the case of urinary stones formation, several species of bacteria may be involved in the process. The purpose of the study was to determine the impact of the bacterial species: Escherichia coli, Klebsiella pneumoniae, Providencia stuartii, Pseudomonas aeruginosa and Staphylococcus aureus on the crystallization caused by Proteus mirabilis. The studies were conducted in synthetic urine with the addition of P. mirabilis and a representative of another species. During the experiments the viability of bacteria, pH, presence and morphology of crystals, and the intensity of crystallization were assessed. Crystallization of calcium and magnesium phosphates occurred in all investigated configurations. However, there were differences observed in the course and intensity of crystallization between the mixed culture and the P. mirabilis culture. Although most intense crystallization took place in the pure culture of P. mirabilis it was also demonstrated that the presence of other uropathogens increased the survival of P. mirabilis. This synergistic effect could be responsible for the persistence and recurrence of urolithiasis in the urinary tract.


Asunto(s)
Cristalización , Interacciones Microbianas , Proteus mirabilis/metabolismo , Orina/química , Orina/microbiología , Coinfección/microbiología , Escherichia coli/patogenicidad , Humanos , Klebsiella pneumoniae/patogenicidad , Viabilidad Microbiana , Minerales , Infecciones Urinarias/microbiología , Urolitiasis/microbiología
19.
Immunobiology ; 223(1): 1-7, 2018 01.
Artículo en Inglés | MEDLINE | ID: mdl-29017822

RESUMEN

Primary cytoreduction, followed by chemotherapy, is a standard treatment of patients with epithelial ovarian cancer (EOC). However, the effectiveness of this treatment depend on various elements e.g. type of operation. It is accepted that optimal surgery correlates with longer survival of patients. The other element, an efficiency of immune system after surgical intervention although important is less elucidated. The aim of this study was to establish the impact of optimal and sub-optimal operation on immunological status of EOC patients regarding also their overall survival (OS). On the day of primary cytoreduction and 7days after, the selected serum immunological parameters were determined in 49 patients with confirmed EOC. We found that, the level of immunosuppressive (interleukin 10; transforming growth factor-ß - TGF-ß1) and pro-inflammatory (interleukin-6 and 8) cytokines was significantly higher in the group of patients with advanced stage of disease, compared to early stage. However, the number of circulating CD3+, CD4+ or CD8+ cells, CD19+ and NK cells was similar in both group of EOC patients. The overall survival of patients who underwent optimal cytoreduction was significantly higher than that in whom only sub-optimal surgery was performed. Sub-optimal cytoreduction only partially weakened the serum level of TGF-ß1 and IL-8 and what is more enhanced the number of circulating CD4+CD25+high cells in patients with advanced stage of disease. Sub-optimal surgery and high post-operative level of TGF-ß1 increased the hazard ratio for patients. Besides, we noticed that the high pre-operative concentration of TGF-ß1 could distinguish all EOC patients (independently of FIGO classification) for whom optimal or sub-optimal surgery would be applied. Sub-optimal debulking resulted in higher immunosuppression and lower OS of EOC patients.


Asunto(s)
Procedimientos Quirúrgicos de Citorreducción , Células Epiteliales/patología , Neoplasias Glandulares y Epiteliales/inmunología , Neoplasias Ováricas/inmunología , Ovario/patología , Complicaciones Posoperatorias/inmunología , Linfocitos T Reguladores/inmunología , Carcinoma Epitelial de Ovario , Femenino , Humanos , Terapia de Inmunosupresión , Interleucina-10/sangre , Interleucina-6/sangre , Interleucina-8/sangre , Persona de Mediana Edad , Neoplasias Glandulares y Epiteliales/mortalidad , Neoplasias Glandulares y Epiteliales/cirugía , Neoplasias Ováricas/mortalidad , Neoplasias Ováricas/cirugía , Ovario/cirugía , Análisis de Supervivencia , Factor de Crecimiento Transformador beta1/sangre , Resultado del Tratamiento , Microambiente Tumoral
20.
Medicine (Baltimore) ; 97(12): e0180, 2018 03.
Artículo en Inglés | MEDLINE | ID: mdl-29561432

RESUMEN

Smouldering inflammation, thrombocytosis, and platelet hyper-reactivity are linked to malignancy. The relationships between preoperative diagnostic blood morphology parameters and cancer have been the focus of much interest, because some of these parameters are correlated with advanced cancer stages and poor patient survival rates. This study aimed to perform an observational, retrospective analysis of the intradiversity of blood platelet parameters in patients with different International Federation of Gynaecology and Obstetrics (FIGO) stages and different histological types of epithelial ovarian carcinomas (EOC), and also an analysis of the overall survival rate.In all, 94 EOC patients were included in this analysis (23 mucinous, 33 serous, 20 undifferentiated, 14 endometrioid, and 4 clear cell carcinoma cases). Peripheral blood samples were collected and analyzed before drug or surgical treatment.The platelet-to-neutrophil ratio (PNR) was related to the histological type of EOC, particularly mucinous carcinoma. In patients with mucinous cancer, the PNR was significantly lower compared with patients with nonmucinous cancer, and this parameter distinguished between mucinous and nonmucinous groups of patients (area under receiver-operating characteristic [ROC] curve 0.721 ±â€Š.056; sensitivity 82.6%; specificity 61%; P < .001; ROC analysis), regardless of the FIGO stage. Moreover, elevated PNR values were correlated with lower survival rate of EOC patients.The reduced PNR, similar to the lower level of cancer antigen 125, is characteristic for mucinous ovarian carcinoma patients. Moreover, elevated PNR index might correlate with poor survival of patients.


Asunto(s)
Plaquetas/patología , Neoplasias Glandulares y Epiteliales/sangre , Neoplasias Glandulares y Epiteliales/patología , Neoplasias Ováricas/sangre , Neoplasias Ováricas/patología , Adulto , Anciano , Anciano de 80 o más Años , Análisis de Varianza , Antígeno Ca-125/sangre , Carcinoma Epitelial de Ovario , Humanos , Proteínas de la Membrana/sangre , Persona de Mediana Edad , Periodo Preoperatorio , Curva ROC , Estudios Retrospectivos , Análisis de Supervivencia , Adulto Joven
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