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1.
Cardiovasc Res ; 120(1): 82-94, 2024 02 27.
Article in English | MEDLINE | ID: mdl-37879102

ABSTRACT

AIMS: Tumour necrosis factor α (TNF-α) represents a classical pro-inflammatory cytokine, and its increased levels positively correlate with the severity of many cardiovascular diseases. Surprisingly, some heart failure patients receiving high doses of anti-TNF-α antibodies showed serious health worsening. This work aimed to examine the role of TNF-α signalling on the development and progression of myocarditis and heart-specific autoimmunity. METHODS AND RESULTS: Mice with genetic deletion of TNF-α (Tnf+/- and Tnf-/-) and littermate controls (Tnf+/+) were used to study myocarditis in the inducible and the transgenic T cell receptor (TCRM) models. Tnf+/- and Tnf-/- mice immunized with α-myosin heavy chain peptide (αMyHC) showed reduced myocarditis incidence, but the susceptible animals developed extensive inflammation in the heart. In the TCRM model, defective TNF-α production was associated with increased mortality at a young age due to cardiomyopathy and cardiac fibrosis. We could confirm that TNF-α as well as the secretome of antigen-activated heart-reactive effector CD4+ T (Teff) cells effectively activated the adhesive properties of cardiac microvascular endothelial cells (cMVECs). Our data suggested that TNF-α produced by endothelial in addition to Teff cells promoted leucocyte adhesion to activated cMVECs. Analysis of CD4+ T lymphocytes from both models of myocarditis showed a strongly increased fraction of Teff cells in hearts, spleens, and in the blood of Tnf+/- and Tnf-/- mice. Indeed, antigen-activated Tnf-/- Teff cells showed prolonged long-term survival and TNF-α cytokine-induced cell death of heart-reactive Teff. CONCLUSION: TNF-α signalling promotes myocarditis development by activating cardiac endothelial cells. However, in the case of established disease, TNF-α protects from exacerbating cardiac inflammation by inducing activation-induced cell death of heart-reactive Teff. These data might explain the lack of success of standard anti-TNF-α therapy in heart failure patients and open perspectives for T cell-targeted approaches.


Subject(s)
Autoimmune Diseases , Heart Failure , Myocarditis , Animals , Mice , CD4-Positive T-Lymphocytes , Cytokines/metabolism , Death , Endothelial Cells/pathology , Heart Failure/metabolism , Inflammation/metabolism , Myocarditis/metabolism , Myocardium/metabolism , Tumor Necrosis Factor Inhibitors , Tumor Necrosis Factor-alpha/metabolism
2.
J Inflamm (Lond) ; 20(1): 26, 2023 Aug 10.
Article in English | MEDLINE | ID: mdl-37563611

ABSTRACT

According to the World Health Organization (WHO), air pollution is one of the most serious threats for our planet. Despite a growing public awareness of the harmful effects of air pollution on human health, the specific influence of particulate matter (PM) on human immune cells remains poorly understood. In this study, we investigated the effect of PM on peripheral blood monocytes in vitro. Monocytes from healthy donors (HD) were exposed to two types of PM: NIST (SRM 1648a, standard urban particulate matter from the US National Institute for Standards and Technology) and LAP (SRM 1648a with the organic fraction removed). The exposure to PM-induced mitochondrial ROS production followed by the decrease of mitochondrial membrane potential and activation of apoptotic protease activating factor 1 (Apaf-1), Caspase-9, and Caspase-3, leading to the cleavage of Gasdermin E (GSDME), and initiation of pyroptosis. Further analysis showed a simultaneous PM-dependent activation of inflammasomes, including NLRP3 (nucleotide-binding oligomerization domain-like receptor pyrin domain containing 3) and Caspase-1, followed by cleavage of Gasdermin D (GSDMD) and secretion of IL-1ß. These observations suggest that PM-treated monocytes die by pyroptosis activated by two parallel signaling pathways, related to the inorganic and organic PM components. The release of IL-1ß and expression of danger-associated molecular patterns (DAMPs) by pyroptotic cells further activated the remnant viable monocytes to produce inflammatory cytokines (TNF-α, IL-6, IL-8) and protected them from death induced by the second challenge with PM.In summary, our report shows that PM exposure significantly impacts monocyte function and induces their death by pyroptosis. Our observations indicate that the composition of PM plays a crucial role in this process-the inorganic fraction of PM is responsible for the induction of the Caspase-3-dependent pyroptotic pathway. At the same time, the canonical inflammasome path is activated by the organic components of PM, including LPS (Lipopolysaccharide/endotoxin). PM-induced pyroptosis of human monocytes. Particulate matter (PM) treatment affects monocytes viability already after 15 min of their exposure to NIST or LAP in vitro. The remnant viable monocytes in response to danger-associated molecular patterns (DAMPs) release pro-inflammatory cytokines and activate Th1 and Th17 cells. The mechanism of PM-induced cell death includes the increase of reactive oxygen species (ROS) production followed by collapse of mitochondrial membrane potential (ΔΨm), activation of Apaf-1, Caspase-9 and Caspase-3, leading to activation of Caspase-3-dependent pyroptotic pathway, where Caspase-3 cleaves Gasdermin E (GSDME) to produce a N-terminal fragment responsible for the switch from apoptosis to pyroptosis. At the same time, PM activates the canonical inflammasome pathway, where activated Caspase-1 cleaves the cytosolic Gasdermin D (GSDMD) to produce N-terminal domain allowing IL-1ß secretion. As a result, PM-treated monocytes die by pyroptosis activated by two parallel pathways-Caspase-3-dependent pathway related to the inorganic fraction of PM and the canonical inflammasome pathway dependent on the organic components of PM.

3.
Food Chem X ; 17: 100619, 2023 Mar 30.
Article in English | MEDLINE | ID: mdl-36974173

ABSTRACT

The present study aimed to evaluate the content of polyphenols and carotenoids as well as the health-promoting properties (antioxidant, antidiabetic, antiobesity, antiaging, and anti-inflammatory activities) in selected peaches cultivated in Poland. The qualitative analysis of the tested cultivars showed that the content of polyphenols was dominated by flavan-3-ols, and phenolic acids. In turn, the performed analysis clearly indicated that the dominant carotenoid was ß-carotene, which constituted on average 88% of the total amount of carotenoids. The general content of yellow pigments is as follows: all-trans-ß-carotene > 13 cis-ß-carotene > 9 cis-ß-carotene > zeaxanthin > ß-cryptoxanthin ≥ ß-cryptoxanthin-myristate > ß-cryptoxanthin-palmitate > crocin ≥ cis-violaxanthin > lutein. In addition, the present study showed that the peach fruit has a high potential in the context of inhibition of pancreatic lipase, which may indicate a potential antiobesity effect. However, the potential of the peaches to inhibit α-amylase, α-glucosidase, or 15-LOX has not been demonstrated.

4.
Foods ; 12(23)2023 Nov 29.
Article in English | MEDLINE | ID: mdl-38231877

ABSTRACT

The main goal of this research was to investigate how particle size influences the characteristics of pear (Pyrus Communis L.) pomace flour and to examine the impact of different pre-treatment methods on the phenolic content and associated bioactivities. Pear pomace flour was fractionated into different particle sizes, namely 1 mm, 710 µm, 180 µm, 75 µm and 53 µm. Then two extraction methods, namely maceration with methanol and two-step extraction with hexane via Soxhlet followed by ultrasound extraction with methanol, were tested. Total phenolic and total flavonoid contents ranged from 375.0 to 512.9 mg gallic acid/100 g DW and from 24.7 to 34.6 mg quercetin/100 g DW, respectively. Two-step extraction provided antioxidant activity up to 418.8 (in FRAP assay) and 340.0 mg Trolox/100 g DW (in DPPH assay). In order to explore various bioactive properties, this study assessed the inhibitory effects of enzymes, specifically α-amylase and ß-glucosidase (associated with antidiabetic effects), as well as angiotensin-converting enzyme (linked to potential antihypertensive benefits). Additionally, the research investigated antibacterial potential against both Gram-negative (E. coli) and Gram-positive (S. aureus) bacteria, revealing significant results (p < 0.05), particularly in the case of the two-step extraction method. This investigation underscores the substantial value of certain food industry wastes, highlighting their potential as bioactive ingredients within the framework of a circular economy.

5.
Food Chem X ; 15: 100418, 2022 Oct 30.
Article in English | MEDLINE | ID: mdl-36211787

ABSTRACT

The aim of the present study was to examine the nutritional (fat, fatty acids, minerals, sugars) and bioactive compounds (polyphenols, tocochromanols, triterpene) and their influence on in vitro anti-diabetic (pancreatic α-amylase and intestinal α-glucosidase), anti-obesity (pancreatic lipase) and anti-cholinergic (AChE and BuChE) inhibitory activity of 8 different popular nuts-pecan, pine, hazelnuts, pistachio, almonds, cashew, walnuts, and macadamia. The total content of phenolic compounds in nuts ranged from 432.9 (walnuts) to 5.9 (pistachio) mg/100 g. The dominant polyphenols are polymeric procyanidins (walnuts - 415.1 mg/100 g). Nuts are rich in tocochromanols (832.9-4377.5 µg/100 g), especially α- and γ-tocopherols. The highest content of α-tocopherol (vitamin E) was detected in hazelnuts and almonds (2551.0 and 2489.7 µg/100 g, respectively) while the lowest amounts were detected in macadamia, cashew and walnuts. The most abundant in nuts are oleanic and pomolic acids (35 and 22 % of total, respectively), while betulin, uvaol and erythrodiol are less characteristic triterpenes for nuts (<1%). Pine nuts are the nuts with the highest content of triterpene (690.3 mg/100 g). Pistachio and almonds are the richest in total fat (>45 %), but monounsaturated (17.5-79.3 %; hazelnuts, almonds, cashew, macadamia, pistachio and pecan) and polyunsaturated (7.5-69.3 %; pine, walnuts) are the dominant fatty acids. Moreover, nuts are low in Cu, Zn, Mn and Na content, but rich in K (464.5-1772.3 mg/100 g) and Mg (197.0-502.5 mg/100 g). Macadamia, walnuts and cashew are good sources of Se. Pistachio, almonds and cashew were characterized by the highest content of sugars, but the dominant sugar was saccharose (58.2-2399.3 mg/100 g). All nuts showed high activity in inhibiting intestinal α-glucosidase (>90 %), but lower ability to inhibit pancreatic α-amylase and pancreatic lipase activity. The activity in inhibiting acetyl- and butylcholinesterase was up to 30 %. As described above, all nuts contain various compounds that improve the nutritional value. Therefore they should be one of the important components of the daily human diet rich in functional foods.

6.
Oxid Med Cell Longev ; 2022: 2457687, 2022.
Article in English | MEDLINE | ID: mdl-36211827

ABSTRACT

Background: Activation of endothelial cells by inflammatory mediators secreted by CD4+ T lymphocytes plays a key role in the inflammatory response. Exosomes represent a specific class of signaling cues transporting a mixture of proteins, nucleic acids, and other biomolecules. So far, the impact of exosomes shed by T lymphocytes on cardiac endothelial cells remained unknown. Methods and Results: Supernatants of CD4+ T cells activated with anti-CD3/CD28 beads were used to isolate exosomes by differential centrifugation. Activation of CD4+ T cells enhanced exosome production, and these exosomes (CD4-exosomes) induced oxidative stress in cardiac microvascular endothelial cells (cMVECs) without affecting their adhesive properties. Furthermore, CD4-exosome treatment aggravated the generation of mitochondrial reactive oxygen species (ROS), reduced nitric oxide (NO) levels, and enhanced the proliferation of cMVECs. These effects were reversed by adding the antioxidant apocynin. On the molecular level, CD4-exosomes increased NOX2, NOX4, ERK1/2, and MEK1/2 in cMVECs, and ERK1/2 and MEK1/2 proteins were found in CD4-exosomes. Inhibition of either MEK/ERK with U0126 or ERK with FR180204 successfully protected cMVECs from increased ROS levels and reduced NO bioavailability. Treatment with NOX1/4 inhibitor GKT136901 effectively blocked excessive ROS and superoxide production, reversed impaired NO levels, and reversed enhanced cMVEC proliferation triggered by CD4-exosomes. The siRNA-mediated silencing of Nox4 in cMVECs confirmed the key role of NOX4 in CD4-exosome-induced oxidative stress. To address the properties of exosomes under inflammatory conditions, we used the mouse model of CD4+ T cell-dependent experimental autoimmune myocarditis. In contrast to exosomes obtained from control hearts, exosomes obtained from inflamed hearts upregulated NOX2, NOX4, ERK1/2, MEK1/2, increased ROS and superoxide levels, and reduced NO bioavailability in treated cMVECs, and these changes were reversed by apocynin. Conclusion: Our results point to exosomes as a novel class of bioactive factors secreted by CD4+ T cells in immune response and represent potential important triggers of NOX4-dependent endothelial dysfunction. Neutralization of the prooxidative aspect of CD4-exosomes could open perspectives for the development of new therapeutic strategies in inflammatory cardiovascular diseases.


Subject(s)
Endothelial Cells , Exosomes , Acetophenones , Animals , Antioxidants/pharmacology , CD28 Antigens/metabolism , Endothelial Cells/metabolism , Exosomes/metabolism , Inflammation Mediators/metabolism , MAP Kinase Signaling System , Mice , Mitogen-Activated Protein Kinase Kinases/metabolism , NADPH Oxidase 4/metabolism , NADPH Oxidases/metabolism , Nitric Oxide/metabolism , Oxidative Stress , RNA, Small Interfering/metabolism , Reactive Oxygen Species/metabolism , Superoxides/metabolism , T-Lymphocytes/metabolism
7.
J Sci Food Agric ; 102(1): 185-197, 2022 Jan 15.
Article in English | MEDLINE | ID: mdl-34061348

ABSTRACT

BACKGROUND: Juices are currently a fast-growing segment in the fruit and vegetable industry sector. However, there are still no reports on the diversity of the phytochemical profile and health-promoting properties of commercial sea buckthorn (Hippophaë rhamnoides) juices. This study aimed to identify and quantify phytoprostanes, phytofurans by ultra high-performance liquid chromatography coupled with triple quadrupole mass spectrometry (UHPLC-QqQ-MS/MS), tocopherols, tocotrienols by ultra-performance liquid chromatography coupled with a fluorescence detector (UPLC-FL), carotenoids, and free amino acids by ultra-performance liquid chromatography coupled with a photodiode detector-quadrupole and tandem time-of-flight mass spectrometry (UPLC-PDA-Q/TOF-MS), and assess their anti-cholinergic, anti-diabetic, anti-obesity, anti-inflammatory, and antioxidant potential by in vitro assays of commercial sea buckthorn juices. RESULTS: Phytoprostanes (PhytoPs) and phytofurans (PhytoFs) in sea buckthorn juices were identified for the first time. Juices contained eight F1 -, D1 -, B1 - and L1 -phytoprostanes and one phytofuran (32.31-1523.51 ng and up to 101.47 µg/100 g dry weight (DW)), four tocopherol congeners (22.23-94.08 mg 100 g-1 DW) and three tocotrienols (5.93-25.34 mg 100 g-1 DW). Eighteen carotenoids were identified, including ten xanthophylls, seven carotenes and phytofluene, at a concentration of 133.65 to 839.89 mg 100 g-1 DW. Among the 20 amino acids (175.92-1822.60 mg 100 g-1 DW), asparagine was dominant, and essential and conditionally essential amino acids constituted 11 to 41% of the total. The anti-enzyme and antioxidant potential of juices correlated selectively with the composition. CONCLUSION: Sea buckthorn juice can be a valuable dietary source of vitamins E and A, oxylipins and amino acids, used in the prevention of metabolic syndrome, inflammation, and neurodegenerative processes. The differentiation of the composition and the bioactive potential of commercial juices indicate that, for the consumer, it should be important to choose juices from the declared berry cultivars and crops. © 2021 Society of Chemical Industry.


Subject(s)
Carotenoids/chemistry , Fruit and Vegetable Juices/analysis , Hippophae/chemistry , Plant Extracts/chemistry , Tocopherols/chemistry , Tocotrienols/chemistry , Amino Acids/chemistry , Antioxidants/chemistry , Chromatography, High Pressure Liquid , Fruit/chemistry , Tandem Mass Spectrometry
8.
Cardiovasc Res ; 118(2): 573-584, 2022 01 29.
Article in English | MEDLINE | ID: mdl-33576779

ABSTRACT

AIMS: Angiotensin (Ang) II signalling has been suggested to promote cardiac fibrosis in inflammatory heart diseases; however, the underlying mechanisms remain obscure. Using Agtr1a-/- mice with genetic deletion of angiotensin receptor type 1 (ATR1) and the experimental autoimmune myocarditis (EAM) model, we aimed to elucidate the role of Ang II-ATR1 pathway in development of heart-specific autoimmunity and post-inflammatory fibrosis. METHODS AND RESULTS: EAM was induced in wild-type (WT) and Agtr1a-/- mice by subcutaneous injections with alpha myosin heavy chain peptide emulsified in complete Freund's adjuvant. Agtr1a-/- mice developed myocarditis to a similar extent as WT controls at day 21 but showed reduced fibrosis and better systolic function at day 40. Crisscross bone marrow chimaera experiments proved that ATR1 signalling in the bone marrow compartment was critical for cardiac fibrosis. Heart infiltrating, bone-marrow-derived cells produced Ang II, but lack of ATR1 in these cells reduced transforming growth factor beta (TGF-ß)-mediated fibrotic responses. At the molecular level, Agtr1a-/- heart-inflammatory cells showed impaired TGF-ß-mediated phosphorylation of Smad2 and TAK1. In WT cells, TGF-ß induced formation of RhoA-GTP and RhoA-A-kinase anchoring protein-Lbc (AKAP-Lbc) complex. In Agtr1a-/- cells, stabilization of RhoA-GTP and interaction of RhoA with AKAP-Lbc were largely impaired. Furthermore, in contrast to WT cells, Agtr1a-/- cells stimulated with TGF-ß failed to activate canonical Wnt pathway indicated by suppressed activity of glycogen synthase kinase-3 (GSK-3)ß and nuclear ß-catenin translocation and showed reduced expression of Wnts. In line with these in vitro findings, ß-catenin was detected in inflammatory regions of hearts of WT, but not Agtr1a-/- mice and expression of canonical Wnt1 and Wnt10b were lower in Agtr1a-/- hearts. CONCLUSION: Ang II-ATR1 signalling is critical for development of post-inflammatory fibrotic remodelling and dilated cardiomyopathy. Our data underpin the importance of Ang II-ATR1 in effective TGF-ß downstream signalling response including activation of profibrotic Wnt/ß-catenin pathway.


Subject(s)
Angiotensin II/metabolism , Autoimmune Diseases/metabolism , Autoimmunity , CD4-Positive T-Lymphocytes/metabolism , Myocarditis/metabolism , Myocytes, Cardiac/metabolism , Receptor, Angiotensin, Type 1/metabolism , Wnt Signaling Pathway , Animals , Autoimmune Diseases/genetics , Autoimmune Diseases/immunology , Autoimmune Diseases/pathology , CD4-Positive T-Lymphocytes/immunology , Cell Proliferation , Cells, Cultured , Disease Models, Animal , Fibrosis , Inflammation Mediators/metabolism , Lymphocyte Activation , Mice, Inbred BALB C , Mice, Knockout , Myocarditis/genetics , Myocarditis/immunology , Myocarditis/pathology , Myocytes, Cardiac/immunology , Myocytes, Cardiac/pathology , Receptor, Angiotensin, Type 1/genetics , Wnt Proteins/genetics , Wnt Proteins/metabolism , Wnt1 Protein/genetics , Wnt1 Protein/metabolism , beta Catenin/genetics , beta Catenin/metabolism
9.
J Sci Food Agric ; 102(4): 1466-1474, 2022 Mar 15.
Article in English | MEDLINE | ID: mdl-34398983

ABSTRACT

BACKGROUND: Nowadays it is highly important to find new, cheap and widely available sources of tocopherol and tocotrienol compounds, and leaves are promising unconventional sources. The main goal of this study was to extend the currently limited knowledge concerning tocopherol and tocotrienol isomers composition determined using ultra-high performance liquid chromatography with fluorescence detection analysis for various fruit tree leaves such as apple, pear, quince, apricot, peach, plum, sour cherry and sweet cherry. The leaves were collected 2 weeks after tree blooming and after fruit collection. Tocopherol and tocotrienol isomers were identified and quantified for the first time in all fruit tree leaves. RESULTS: The total tocopherol content ranged from 203.34 to 260.86 µg g-1 dry weight for spring leaves and from 23.83 to 235.62 µg g-1 dry weight for autumn leaves and consisted mainly of α-tocopherol. The rest of the isomers of tocopherol and tocotrienols were also found, but in trace amounts. A significantly lower content of tocopherols and tocotrienols was detected in leaves after autumn collection of fruits compared to leaves collected after blooming. Among the analyzed leaves, time collected and species were significantly more important than their cultivars. Regarding quantification analysis, apricot > peach > > plums > apples leaves were identified as the best sources of tocopherols, and sweet and sour cherry leaves exhibited a lower content. CONCLUSION: Fruit tree leaves are a novel significant source and good material for isolation of α-tocopherol for application in cosmetics, pharmaceuticals or in the food industry - for example, production of beverages or other functional foods. © 2021 Society of Chemical Industry.


Subject(s)
Tocotrienols , Fruit , Tocopherols , Trees , Vitamin E
10.
Molecules ; 26(24)2021 Dec 15.
Article in English | MEDLINE | ID: mdl-34946676

ABSTRACT

The functional food market has been in a state of constant expansion due to the increasing awareness of the impact of the diet on human health. In the search for new natural resources that could act as a functional ingredient for the food industry, microalgae represent a promising alternative, considering their high nutritional value and biosynthesis of numerous bioactive compounds with reported biological properties. In the present work, the phytochemical profile, antioxidant activity, and enzymatic inhibitory effect aiming at different metabolic disorders (Alzheimer's disease, Type 2 diabetes, and obesity) were evaluated for the species Porphyridium purpureum, Chlorella vulgaris, Arthorspira platensis, and Nannochloropsis oculata. All the species presented bioactive diversity and important antioxidant activity, demonstrating the potential to be used as functional ingredients. Particularly, P. purpureum and N. oculata exhibited higher carotenoid and polyphenol content, which was reflected in their superior biological effects. Moreover, the species P. purpureum exhibited remarkable enzymatic inhibition for all the analyses.


Subject(s)
Antioxidants , Enzyme Inhibitors , Microalgae/chemistry , Animals , Antioxidants/chemistry , Antioxidants/pharmacology , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/pharmacology , Swine
11.
Sci Rep ; 11(1): 20253, 2021 10 12.
Article in English | MEDLINE | ID: mdl-34642358

ABSTRACT

This paper presents characterization of healthy potential new sources of functional constituents with reference to basic plant sources. In this study, the phenolics, triterpene, isoprenoids (chlorophylls and carotenoids), amino acids, minerals, sugars and organic acids of different cultivars of pome species-apple, pear, quince-leaves vs. fruits and their enzymatic in vitro enzyme inhibition of hyperglycemic (α-glucosidase, α-amylase), obesity (pancreatic lipase), cholinesterase (acetylcholinesterase, butylcholinesterase), inflammatory (15-LOX, COX-1 and -2) and antioxidant capacity (ORAC, FRAP, ABTS) were evaluated. Leaves of pome species as a new plant sources were characterized by higher content of bioactive and nutritional compounds than basic fruits. The dominant fraction for quince, pear, and apple fruits was polymeric procyanidins. In quince and pear leaves flavan-3-ols, and in apple dihydrochalcones dominated. Triterpene was present in equal content in leaves and fruits. Leaves are excellent sources of amino acids and minerals (especially Ca, Mg, Fe, and K), with high content of organic acids and low content of sugars compared to fruits of pome species. Leaves of apples and pears most effectively inhibited COX-1, COX-2, α-amylase, and α-glucosidase enzyme but quince leaves showed the most effective inhibition of pancreatic lipase, AChE and BuChE, 15-LOX, and antioxidant capacity, which particularly correlated with bioactive compounds. Present study shows that leaves are promising sources of valuable compounds and may be used to produce functional foods as well as for medical purposes.


Subject(s)
Malus/chemistry , Phytochemicals/pharmacology , Pyrus/chemistry , Rosaceae/chemistry , Antioxidants/chemistry , Antioxidants/pharmacology , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/pharmacology , Flavonoids/chemistry , Flavonoids/pharmacology , Fruit/chemistry , Functional Food , Health Promotion , Phytochemicals/chemistry , Plant Leaves/chemistry , Proanthocyanidins/chemistry , Proanthocyanidins/pharmacology
12.
Int J Mol Sci ; 22(18)2021 Sep 17.
Article in English | MEDLINE | ID: mdl-34576234

ABSTRACT

Cardiac fibrosis is a pathological process associated with the development of heart failure. TGF-ß and WNT signaling have been implicated in pathogenesis of cardiac fibrosis, however, little is known about molecular cross-talk between these two pathways. The aim of this study was to examine the effect of exogenous canonical WNT3a and non-canonical WNT5a in TGF-ß-activated human cardiac fibroblasts. We found that WNT3a and TGF-ß induced a ß-catenin-dependent response, whereas WNT5a prompted AP-1 activity. TGF-ß triggered profibrotic signatures in cardiac fibroblasts, and co-stimulation with WNT3a or co-activation of the ß-catenin pathway with the GSK3ß inhibitor CHIR99021 enhanced collagen I and fibronectin production and development of active contractile stress fibers. In the absence of TGF-ß, neither WNT3a nor CHIR99021 exerted profibrotic responses. On a molecular level, in TGF-ß-activated fibroblasts, WNT3a enhanced phosphorylation of TAK1 and production and secretion of IL-11 but showed no effect on the Smad pathway. Neutralization of IL-11 activity with the blocking anti-IL-11 antibody effectively reduced the profibrotic response of cardiac fibroblasts activated with TGF-ß and WNT3a. In contrast to canonical WNT3a, co-activation with non-canonical WNT5a suppressed TGF-ß-induced production of collagen I. In conclusion, WNT/ß-catenin signaling promotes TGF-ß-mediated fibroblast-to-myofibroblast transition by enhancing IL-11 production. Thus, the uncovered mechanism broadens our knowledge on a molecular basis of cardiac fibrogenesis and defines novel therapeutic targets for fibrotic heart diseases.


Subject(s)
Fibroblasts/metabolism , Interleukin-11/metabolism , Myocardium/metabolism , Transforming Growth Factor beta1/metabolism , Wnt Proteins/metabolism , beta Catenin/metabolism , Collagen/chemistry , Collagen/metabolism , Fibrosis/pathology , Heart/physiology , Humans , MAP Kinase Kinase Kinases/metabolism , Myofibroblasts/metabolism , RNA-Seq , Signal Transduction , Stress Fibers/metabolism , Wnt Signaling Pathway/drug effects , Wnt-5a Protein/metabolism , Wnt3A Protein/metabolism
13.
Foods ; 10(9)2021 Aug 25.
Article in English | MEDLINE | ID: mdl-34574101

ABSTRACT

This study aimed to evaluate the feasibility of microencapsulating chokeberry extract by extrusion, and assess the effects of the selected carrier substance on the contents of polyphenolic compounds, antioxidant activity, color of microspheres, and ability of microspheres to inhibit α-amylase and α-glucosidase, after 14 and 28 days of storage. The results showed that appropriate selection of the polysaccharide coating is of great importance for the proper course of the microencapsulation process, the polyphenolic content of chokeberry capsules, and their antioxidant and antidiabetic properties. The addition of guar gum to a sodium alginate solution significantly increased the stability of polyphenolic compounds in microspheres during storage, whereas the addition of chitosan had a significantly negative effect on the stability of polyphenols. The coating variant composed of sodium alginate and guar gum was also found to be the most favorable for the preservation of the antioxidant activity of the capsules. On the other hand, capsules composed of sodium alginate, guar gum, and chitosan showed the best antidiabetic properties, which is related to these tricomponent microspheres having the best α-glucosidase inhibition.

14.
Br Dent J ; 231(4): 225-231, 2021 08.
Article in English | MEDLINE | ID: mdl-34446893

ABSTRACT

'Necrotising periodontal diseases' is an umbrella term for necrotising gingivitis, necrotising periodontitis, necrotising stomatitis and noma. These rapidly destructive conditions are characterised by pain, interdental ulceration and gingival necrosis which, if left untreated, can result in osteonecrosis. Research indicates that patients with a history of alcohol misuse are at an increased risk of malnutrition, which negatively affects the immune response and predisposition to necrotising periodontal diseases. This article will discuss that osteonecrosis of the alveolar bone does not exclusively occur in association with antiresorptive medications, but can occur as a severe form of necrotising gingivitis. In this article, we will describe two cases to highlight the occurrence, presentation and management of necrotising periodontal diseases secondary to alcohol misuse.


Subject(s)
Alcoholism , Gingivitis, Necrotizing Ulcerative , Gingivitis , Noma , Osteonecrosis , Periodontal Diseases , Alcoholism/complications , Gingivitis, Necrotizing Ulcerative/etiology , Gingivitis, Necrotizing Ulcerative/therapy , Humans , Osteonecrosis/chemically induced , Osteonecrosis/therapy
15.
Food Chem ; 349: 129156, 2021 Jul 01.
Article in English | MEDLINE | ID: mdl-33581431

ABSTRACT

This study focused on the identification (by LC-PDA-qTof-ESI-MS) and quantification (by UPLC-PDA) of isoprenoids of the fruit tree leaves (FTL) of commonly consumed fruits: apple, pears, quince, apricot, peach, plums, sweet and sour cherry. The FTL were collected at 2 time points: after tree blooming and after fruit collection. In FTL 7 carotenoids and 16 chlorophylls were identified, but the number of labeled chlorophyll compounds depended on the species. FTL of apple, sour cherry and apricot were identified as the best sources of chlorophylls (mean 404.8, 388.7 and 364.5 mg/100 g dw, respectively) and sweet and sour cherry leaves as the best sources of carotenoids (831.4 and 1162.0 mg/100 g dw, respectively). A lower content of chlorophylls and carotenoids, but not significantly, was detected in leaves after autumn collection of fruits compared to leaves collected after blooming. Fruit tree leaves are good material for isolation of chlorophylls and carotenoids for application in cosmetics, pharmaceuticals or in the food industry, e.g. production of beverages or puree.


Subject(s)
Carotenoids/analysis , Chlorophyll/analysis , Chromatography, Liquid , Fruit/chemistry , Plant Leaves/chemistry , Spectrometry, Mass, Electrospray Ionization , Trees/chemistry , Malus/chemistry , Rosaceae/chemistry , Terpenes/analysis
16.
Food Chem ; 338: 128105, 2021 Feb 15.
Article in English | MEDLINE | ID: mdl-33092003

ABSTRACT

Sea buckthorn berries fit into the strategy of seeking natural factors in the non-communicable diseases prevention, but their sensory qualities are a challenge for consumers and food industry. The study aimed to evaluate anti-cholinesterase (anti-acetylcholinesterase and -butylcholinesterase), anti-diabetic (anti-α-amylase, -α-glucosidase, -pancreatic lipase) and antioxidant potential (FRAP, ORAC), phenolic compounds (UPLC-PDA-FL), basic chemical composition, and sensory quality of sea buckthorn-based smoothies. Eighteen novel products containing sea buckthorn (25-50%) with other fruits and vegetables were analyzed. Sea buckthorn enriched the smoothies in flavonols (25.46-95.13 mg/100 g), and fruits and vegetables provided phenolic acids and procyanidins. The anti-BuChE effect was higher than anti-AChE, while products with apricot, orange, grape and parsley root were strong inhibitors of carbohydrates digesting enzymes. Lipase inhibition by all smoothies was over 50%. Products with 75% fruits or 50% vegetables were the most sensory attractive. The results will be valuable in designing innovative food with rarely used berries.


Subject(s)
Antioxidants/analysis , Beverages , Cholinesterase Inhibitors/analysis , Fruit/chemistry , Hippophae/chemistry , Hypoglycemic Agents/analysis , Taste , Humans
17.
J Sci Food Agric ; 101(6): 2294-2303, 2021 Apr.
Article in English | MEDLINE | ID: mdl-33006384

ABSTRACT

BACKGROUND: Obesity and type 2 diabetes mellitus are the most extended current chronic diseases and also Alzheimer pathology which is a progressive degenerative neurological disorder. Therefore, finding effective enzyme inhibitors responsible for the development of these diseases are essential. Therefore, the aim of this study was to investigate the impact of fruit purée (Cydonia oblonga, Ziziphus jujube and Malus domestica) and pomegranate juice cultivar ('Mollar de Elche' and 'Wonderful') of dried pomegranate sheets (DS) on the inhibition of enzymes associated with metabolic (α-amylase, α-glucosidase, and pancreatic lipase activity), and neurological disorder (acetylcholinesterase and butyrylcholinesterase activity). Quality properties (colour coordinates, texture properties and sensory characteristics) of DS were also studied. In addition, it was researched the effect of storage conditions (4 months at 4 and 20 °C) on phenolic content. RESULTS: DS from jujube had the highest antioxidant capacity and were characterized by the highest storage stability with respect to phenolic compounds. The α-amylase and α-glucosidase half maximal inhibitory concentration (IC50 , in mg mL-1 ) inhibition of DS ranged from 107 to 216 and from 55.2 to values indicating no effect, respectively. The inhibition toward pancreatic lipase (IC50 < 5 mg mL-1 ), acetylcholinesterase (ranged 9.15-22.2%) and butyrylcholinesterase (ranged 20.6-48.6%) was increased with the presence of total flavonoids and hydroxycinnamic acids content (identifying mainly in DS from quinces). It is noteworthy that none of the samples presented off-flavour notes, supporting the high quality of the products. CONCLUSION: DS can be an innovative supplement to a diet as a snack used in the prevention of neurological changes and disorders of carbohydrate and lipid metabolism. © 2020 Society of Chemical Industry.


Subject(s)
Alzheimer Disease/enzymology , Diabetes Mellitus, Type 2/enzymology , Enzyme Inhibitors/chemistry , Fruit and Vegetable Juices/analysis , Fruit/chemistry , Plant Preparations/chemistry , Pomegranate/chemistry , Acetylcholinesterase/chemistry , Butyrylcholinesterase/chemistry , Cholinesterase Inhibitors/chemistry , Humans , Lipase/antagonists & inhibitors , Lipase/chemistry , Malus/chemistry , Rosaceae/chemistry , Ziziphus/chemistry , alpha-Amylases/antagonists & inhibitors , alpha-Amylases/chemistry , alpha-Glucosidases/chemistry
18.
Molecules ; 25(20)2020 Oct 12.
Article in English | MEDLINE | ID: mdl-33053861

ABSTRACT

The aim of the study was to analyze potential health-promoting and nutritional components (polyphenols, L-ascorbic acid, carotenoids, chlorophylls, amino acids, organic acid, sugars, ash and pectins) of selected sprouts (radish, lentil, black medick, broccoli, sunflower, leek, beetroot, mung beans) and microgreens (kale, radish, beetroot, green peas, amaranth). Moreover, antioxidant capacity (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS), ferric reducing ability of plasma (FRAP), and oxygen radical absorbance capacity (ORAC)), in vitro anti-diabetic potential (inhibition of α-amylase and α-glucosidase), and anti-obesity (pancreatic lipase) and anti-cholinergic (acetylcholinesterase and butyrylcholinesterase) activity were evaluated. The results of this study show that sprouts are effective in antioxidant capacity as a result of a high content of polyphenols and L-ascorbic acid. Additionally, sprouts are better sources of amino acids, pectins and sugars than microgreens. Microgreens were characterized by high content of carotenoids and chlorophylls, and organic acid, without any sugars, exhibiting higher anti-diabetic and anti-cholinergic activity than sprouts. Some selected sprouts (broccoli, radish, lentil) and microgreens (radish, amaranths, kale) should be used daily as superfoods or functional food.


Subject(s)
Functional Food , Phytochemicals/analysis , Amino Acids/analysis , Antioxidants/analysis , Ascorbic Acid/analysis , Carotenoids/analysis , Oxygen Radical Absorbance Capacity , Polyphenols/analysis
19.
Foods ; 9(9)2020 Sep 01.
Article in English | MEDLINE | ID: mdl-32883021

ABSTRACT

The World Health Organization (WHO) and the Food and Agriculture Organization of the United Nations (FAO) constantly emphasize the importance of increasing fruit and vegetable consumption; these natural products help in the prevention of major diseases. Smoothies are a simple and convenient way of doing so; thus, their demand is constantly growing and their market is becoming important for the food industry. Therefore, the objective of this research was to determine Millennial consumer opinion towards novel fruit- and vegetable-smoothies available on the retail market. Napping®, descriptive sensory analysis, and consumer studies were conducted. Napping® results group samples into four clusters of smoothies; the main grouping factor was the type of fruit and the percentage of vegetables. Penalty analysis showed that smoothies need improvement mainly dealing with sweetness, bitterness, and vegetable flavors. Millennial consumers formed a homogeneous sensory group in which the overall liking was negatively correlated with the level of sweetness, and earthy, carrot, beetroot, and pear flavors. The key liking drivers were sourness and notes of mango, banana, and peach flavors. This research is a new insight into the perception of smoothies, provides comprehensive knowledge for the food industry, and can guide the design of new healthy smoothies.

20.
Molecules ; 25(17)2020 Aug 21.
Article in English | MEDLINE | ID: mdl-32825580

ABSTRACT

Sea buckthorn (Hippophaë rhamnoides L.) juice with inulin, maltodextrin, and inulin:maltodextrin (1:2 and 2:1) were spray-, freeze- and vacuum-dried at 50, 70 and 90 °C. The study aimed to assess the impact of drying methods and carrier agents on physical properties (moisture content, water activity, true and bulk density, porosity, color parameters, browning index), chemical components (hydroxymethylfurfural and phenolic compounds) and antioxidant capacity of sea buckthorn juice powders. Storage of powders was carried out for six months. Inulin caused stronger water retention in powders than maltodextrin. Vacuum drying provided powders with the highest bulk density. Maltodextrin did not promote browning and HMF formation as strongly as inulin. More phenolic compounds were found in powders with maltodextrin. Storage increased the antioxidant capacity of powders. The results obtained will be useful in optimizing the powders production on an industrial scale, designing attractive food ingredients.


Subject(s)
Antioxidants/analysis , Desiccation/methods , Fruit and Vegetable Juices/analysis , Hippophae/chemistry , Plant Extracts/analysis , Plant Extracts/chemistry , Powders/chemistry , Food Handling , Freeze Drying , Hygroscopic Agents/chemistry , Inulin/chemistry , Polysaccharides/chemistry
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