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Comparison of Phenolic Metabolites in Purified Extracts of Three Wild-Growing Herniaria L. Species and Their Antioxidant and Anti-Inflammatory Activities In Vitro.
Kozachok, S, Kolodziejczyk-Czepas, J, Marchyshyn, S, Wojtanowski, KK, Zgórka, G, Oleszek, W
Molecules (Basel, Switzerland). 2022;(2)
Abstract
The work is aimed at phytochemical characterization and In Vitro evaluation of antioxidant actions, anti-inflammatory effects, and cytotoxicity of purified extracts from three rupturewort (Herniaria L.) species, i.e., Herniaria glabra (HG), H. polygama (HP), and H. incana herb (HIh). The total phenolic content established in the purified extracts (PEs) of HIh, HP, and HG was 29.6, 24.0, and 13.0%, respectively. Thirty-eight non-saponin metabolites were identified using LC-HR-QTOF-ESI-MS; however, only 9 were common for the studied Herniaria species. The most abundant phenolic compound in HG-PE was narcissin (7.4%), HP-PE shared 3 major constituents, namely cis-2-hydroxy-4-methoxycinnamic acid 2-O-β-glucoside (cis-GMCA, 5.8%), narcissin (5.4%), and rutin (5.3%). Almost half of HIh phenolic content (14.7%) belonged to oxytroflavoside A (7-O-methylkaempferol-3-O-[3-hydroxy-3-methylglutaryl-(1→6)]-[α-rhamnopyranosyl-(1→2)]-β-galactopyranoside). Antioxidant properties of the Herniaria PEs were evaluated employing an experimental model of human blood plasma, exposed to the peroxynitrite-induced oxidative stress. The assays demonstrated significant reduction of oxidative damage to protein and lipid plasma components (estimated by measurements of 3-nitrotyrosine, protein thiol groups, thiobarbituric acid-reactive substances), and moderate protection of its non-enzymatic antioxidant capacity. Anti-inflammatory properties of the Herniaria PEs were evaluated In Vitro as inhibitory effects against cyclooxygenases (COX-1 and -2) and concanavalin A-induced inflammatory response of the peripheral blood mononuclear cells (PBMCs). None of the studied plants showed inhibitory effects on COXs but all purified extracts partly reduced the release of interleukin 2 (IL-2) and tumor necrosis factor-alpha (TNF-α) from PBMCs, which suggested their prospective ability to up-regulate inflammatory response of the cells. The purified extract from H. glabra turned out to be the most efficient suppressor of PBMCs' inflammatory response. Additionally, cytotoxicity of purified Herniaria extracts on PBMCs was ruled out based on In Vitro studies.
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The effects of glutamine supplementation on markers of apoptosis and autophagy in sickle cell disease peripheral blood mononuclear cells.
Walter, PB, Hohman, LS, Rokeby, A, Lum, JJ, Hagar, R, Lavrisha, L, Saulys, A, Kuypers, FA, Vichinsky, E, Morris, CR
Complementary therapies in medicine. 2022;:102856
Abstract
OBJECTIVES L-Glutamine was FDA-approved for sickle cell disease (SCD) in 2017, yet the mechanism(s)-of-action are poorly understood. This study investigates the potential activation of autophagy as a previously unexplored mechanism-of-benefit. DESIGN Prospective, open-label, 8-week, phase-2 trial of oral L-glutamine (10 g TID) in patients with SCD at risk for pulmonary hypertension identified by Doppler-echocardiography by an elevated tricuspid-regurgitant-jet-velocity (TRV)≥ 2.5 m/s. Peripheral blood mononuclear cells (PBMCs) were isolated from blood samples taken from SCD patients at baseline, two, four, six and eight weeks of glutamine therapy, and from controls at baseline; BAX (pro-apoptotic marker) and LC3-II/LC3-I (autophagy marker) were measured via western blot analysis to assess apoptosis and autophagy respectively. SETTING Comprehensive SCD Center in Oakland, California. RESULTS Patients with SCD (n = 8) had a mean age of 44 ± 16, 50% were male; 63% Hb-SS, and mean TRV= 3.1 ± 0.7 m/s. Controls' mean age (n = 5) was 32 ± 12% and 57% were male; all were Hb-AA with a mean TRV= 1.8 ± 0.6. At baseline, SCD-PBMCs had 2-times higher levels of BAX and LC3-I versus controls (both p = 0.03). Levels of BAX expression increased by 300% after 8-weeks of glutamine supplementation (p = 0.005); LC3-I protein levels decreased while LC3-II levels increased by 70%, giving a significant increase in the LC3-II/LC3-I ratio (p = 0.02). CONCLUSION PBMCs from glutamine-supplemented SCD patients have upregulated apoptotic and autophagy proteins. The parallel increase in BAX and the LC3-II / LC3-I ratio with glutamine supplementation suggest a possible role of autophagic cell death. The increase in apoptotic markers provide insight into a possible mechanism used by peripheral PBMCs during glutamine supplementation in patients with SCD.
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Four weeks of spice consumption lowers plasma proinflammatory cytokines and alters the function of monocytes in adults at risk of cardiometabolic disease: secondary outcome analysis in a 3-period, randomized, crossover, controlled feeding trial.
Oh, ES, Petersen, KS, Kris-Etherton, PM, Rogers, CJ
The American journal of clinical nutrition. 2022;(1):61-72
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Abstract
BACKGROUND Numerous studies demonstrate acute anti-inflammatory properties of individual spices, but none have examined the effect of longer-term consumption of a spice blend incorporated in a meal. OBJECTIVES We investigated the effect of longer-term spice consumption on inflammatory cytokines and monocyte subsets [classical (CM), intermediate (IM), nonclassical (NCM)] in adults at risk of cardiometabolic disease. METHODS A 3-period, randomized, crossover, controlled feeding trial was conducted. Participants (n = 71 recruited; n = 63 completed) randomly consumed diets differing in terms of the quantity of spices: 0.547 g (low-dose spice diet; LSD), 3.285 g (medium-dose spice diet; MSD), or 6.571 g (high-dose spice diet; HSD) · d-1 · 2100 kcal-1, for 4 wk with a ≥2-wk washout between diets. At baseline and after each diet period, proinflammatory cytokines (IL-1β, IL-6, IL-8, monocyte chemoattractant protein-1, and TNF-α) in plasma and LPS-stimulated peripheral blood mononuclear cell culture supernatants, and the phenotype and function of monocyte subsets, were measured in fasted participants. Postprandial proinflammatory cytokines also were quantified at baseline by consumption of a low-spice-dose test meal, and after each diet period by consumption of a test meal containing a spice dose corresponding to daily spice consumption during the preceding 4-wk diet period. RESULTS Fasting plasma IL-6 was reduced (mean ± SEM: -118.26 ± 50.63 fg/mL; P < 0.05) after MSD compared with baseline. Postprandial plasma IL-1β, IL-8, and TNF-α were lower (mean ± SEM -9.47 ± 2.70 fg/mL, -0.20 ± 0.05 pg/mL, and -33.28 ± 12.35 fg/mL, respectively) after MSD compared with LSD (main diet effect; P < 0.05). CM adherence was reduced (mean ± SEM: -0.86 ± 0.34; P = 0.034) after HSD compared with LSD. IM migration was reduced after MSD and HSD compared with LSD (mean ± SEM: -0.39 ± 0.09 and -0.56 ± 0.14, respectively; P < 0.05). CONCLUSIONS Four weeks of MSD consumption reduced fasting plasma IL-6 and postprandial plasma IL-1β, IL-8, and TNF-α as well as altering monocyte function.This trial was registered at clinicaltrials.gov as NCT03064932.
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Spectrally and Time-Resolved Fluorescence Imaging of 22-NBD-Cholesterol in Human Peripheral Blood Mononuclear Cells in Chronic Kidney Disease Patients.
Lajdova, I, Ovsonkova, L, Spustova, V, Oksa, A, Chorvat, D, Mateasik, A, Marcek Chorvatova, A
Molecules (Basel, Switzerland). 2021;(22)
Abstract
The interaction of the fluorescent probe 22-NBD-cholesterol with membranes of human peripheral blood mononuclear cells (PBMC) was tested by time- and spectrally resolved fluorescence imaging to monitor the disturbance of lipid metabolism in chronic kidney disease (CKD) and its treatment with statins. Blood samples from healthy volunteers (HV) and CKD patients, either treated or untreated with statins, were compared. Spectral imaging was done using confocal microscopy at 16 spectral channels in response to 458 nm excitation. Time-resolved imaging was achieved by time-correlated single photon counting (TCSPC) following excitation at 475 nm. The fluorescence of 22-NBD-cholesterol was mostly integrated into plasmatic membrane and/or intracellular membrane but was missing from the nuclear region. The presence of two distinct spectral forms of 22-NBD-cholesterol was uncovered, with significant variations between studied groups. In addition, two fluorescence lifetime components were unmasked, changing in CKD patients treated with statins. The gathered results indicate that 22-NBD-cholesterol may serve as a tool to study changes in the lipid metabolism of patients with CKD to monitor the effect of statin treatment.
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The effect of moderate wine consumption on cytokine secretion by peripheral blood mononuclear cells: A randomized clinical study in coronary heart disease patients.
Fragopoulou, E, Argyrou, C, Detopoulou, M, Tsitsou, S, Seremeti, S, Yannakoulia, M, Antonopoulou, S, Kolovou, G, Kalogeropoulos, P
Cytokine. 2021;:155629
Abstract
Many studies conclude that wine consumption is related to lower risk for cardiovascular diseases partially through the amelioration of inflammatory biomarkers. The aim of the present study was to examine the effects of wine consumption on the inflammatory response and to compare these effects with the consumption of similar amount of alcohol without the wine micro-constituents in cardiovascular disease patients. Therefore, a randomized, single-blind, controlled, three-arm parallel intervention study was designed. Cardiovascular disease patients were randomly assigned to one of the three groups. In Group A participants consumed no alcohol, in Group B (ethanol group) and Group C (wine group) participants consumed 27 g of alcohol per day. Biological samples were collected at the beginning, on the 4th and 8th week and several biomarkers were measured. Peripheral blood mononuclear cells that were isolated from patients were incubated under basal and inflammatory conditions for 4 and 24 h and the secretion of interleukin 1β (IL-1β) and tumor necrosis factor α (TNFα) was measured. No significant difference was observed among the three groups before the initiation or during the intervention in the most soluble biomarkers. Higher TNFα secretion by peripheral blood mononuclear cells was observed at basal conditions in the ethanol group both at 4 and 24 h of incubation versus baseline secretion. Furthermore, lower secretion of the ΤNFα was observed after 8 weeks of intake in the wine group versus the ethanol group, both at 4 and 24 h of incubation. In conclusion, the light to moderate wine consumption for 8 weeks revealed an attenuation of the ethanol consumption effect on cytokine secretion at basal conditions from the patients' peripheral blood mononuclear cells.
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Impairment of effector molecules response in diabetes induces susceptibility to Leishmania amazonensis infection.
Silva, TF, Gonçalves, MD, Concato, VM, Bortoleti, BTDS, Tomiotto-Pellissier, F, Sanfelice, RA, Rodrigues, ACJ, Detoni, MB, Simão, ANC, Custodio, LA, et al
Immunology letters. 2021;:58-65
Abstract
Type 2 Diabetes is a chronic disease resulting from insulin dysfunction that triggers a low-grade inflammatory state and immune impairment. Leishmaniasis is an infectious disease characterized by chronic inflammation resulted from the parasite's immunomodulation ability. Thus, due to the delicate immune balance required in the combat and resistance to Leishmania infection and the chronic deregulation of the inflammatory response observed in type 2 diabetes, we evaluated the response of PBMC from diabetic patients to in vitro Leishmania amazonensis infection. For that, peripheral blood was collected from 25 diabetic patients and 25 healthy controls matched for age for cells extraction and subsequent experimental infection for 2 or 24 h and analyzed for phagocytic and leishmanicidal capacity by optical microscopy, oxidative stress by GSSG generation, labeling of intracellular mediators by enzyme-Linked immunosorbent assay, and cytokines measurement with cytometric beads array technique. We found that the diabetic group had a higher percentage of infected cells and a greater number of amastigotes per cell. Also, even inducing NF-kB phosphorylation and increasing TNF production after infection, cells from diabetic patients were unable to downregulate NRF2 and generate oxidative stress, which may be associated with the exacerbated levels of IL-6 observed. PBMC of diabetic individuals are more susceptible to infection by L. amazonensis and fail to control the infection over time due to the inability to generate effector microbicidal molecules.
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Maternal diet and offspring telomere length: a systematic review.
Habibi, N, Bianco-Miotto, T, Phoi, YY, Jankovic-Karasoulos, T, Roberts, CT, Grieger, JA
Nutrition reviews. 2021;(2):148-159
Abstract
CONTEXT Many studies assert a negative influence of inappropriate maternal diet and nutritional status during pregnancy on offspring, not only in utero but throughout life, because of the role in the programing of noncommunicable diseases. Telomere length is a biomarker of aging, and shorter telomeres are associated with chronic disease later in life. Maternal nutrition and nutritional status may be an important determinant of offspring telomere length. OBJECTIVE A systematic review was conducted to determine the effect of maternal nutrition and nutritional status in pregnancy on offspring telomere length. DATA SOURCES This systematic review was conducted according to PRISMA guidelines. Database searches of PubMed, CINAHL, Scopus, Medline, and Web of Science were performed. STUDY SELECTION Included studies assessed the association between maternal nutrition (dietary intake and nutritional status) during pregnancy and offspring telomere length measured in cord blood, serum, plasma, and peripheral blood mononuclear cells. DATA EXTRACTION Three authors screened and determined the quality of the articles; disagreements were resolved by a fourth author. All authors compared the compiled data. RESULTS Seven studies were extracted and evaluated. Studies comprised a double-blind placebo-controlled trial (n = 1), prospective cohort studies (n = 5), and a cross-sectional study (n = 1). Higher circulating maternal folate and 25-hydroxyvitamin D3 concentrations, along with higher maternal dietary caffeine intakes, were associated with longer offspring telomere length, whereas higher dietary intake of carbohydrate, folate, n-3 polyunsaturated fatty acids, vitamin C, or sodium was not. CONCLUSION The limited but suggestive evidence highlights the need for further research to be conducted in this area, particularly longitudinal studies involving larger cohorts of pregnant women. SYSTEMATIC REVIEW REGISTRATION PROSPERO registration no. CRD42019136506.
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Adenosine A2A Receptors Are Upregulated in Peripheral Blood Mononuclear Cells from Atrial Fibrillation Patients.
Godoy-Marín, H, Duroux, R, Jacobson, KA, Soler, C, Colino-Lage, H, Jiménez-Sábado, V, Montiel, J, Hove-Madsen, L, Ciruela, F
International journal of molecular sciences. 2021;(7)
Abstract
Atrial fibrillation (AF) is the most common form of cardiac arrhythmia seen in clinical practice. While some clinical parameters may predict the transition from paroxysmal to persistent AF, the molecular mechanisms behind the AF perpetuation are poorly understood. Thus, oxidative stress, calcium overload and inflammation, among others, are believed to be involved in AF-induced atrial remodelling. Interestingly, adenosine and its receptors have also been related to AF development and perpetuation. Here, we investigated the expression of adenosine A2A receptor (A2AR) both in right atrium biopsies and peripheral blood mononuclear cells (PBMCs) from non-dilated sinus rhythm (ndSR), dilated sinus rhythm (dSR) and AF patients. In addition, plasma adenosine content and adenosine deaminase (ADA) activity in these subjects were also determined. Our results revealed increased A2AR expression in the right atrium from AF patients, as previously described. Interestingly, increased levels of adenosine content and reduced ADA activity in plasma from AF patients were detected. An increase was observed when A2AR expression was assessed in PBMCs from AF subjects. Importantly, a positive correlation (P=0.001) between A2AR expression in the right atrium and PBMCs was observed. Overall, these results highlight the importance of the A2AR in AF and suggest that the evaluation of this receptor in PBMCs may be potentially be useful in monitoring disease severity and the efficacy of pharmacological treatments in AF patients.
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Diurnal variation in gene expression of human peripheral blood mononuclear cells after eating a standard meal compared with a high protein meal: A cross-over study.
Davis, R, Murgia, C, Dordevic, AL, Bonham, MP, Huggins, CE
Clinical nutrition (Edinburgh, Scotland). 2021;(6):4349-4359
Abstract
BACKGROUND & AIMS Eating at night has been linked to impaired glucose metabolism and dyslipidaemia that is likely a consequence of an underlying disrupted circadian rhythm in metabolic processes. The aim of this study was to explore the gene expression differences after eating a standard test meal or high protein test meal at night compared with the same meal in the morning. METHODS In a cross over design, 10 healthy adults fasted for >10 h and then completed four acute meal challenges at 8am and 8pm on non-consecutive days separated by a wash out, consuming either a high protein low carbohydrate test meal or an isocaloric standard protein and carbohydrate test meal. Fasting and two-hour postprandial blood samples were collected to measure gene expression. For a subset of five participants RNA sequencing was completed on the Illumina NextSeq500. RESULTS The time of day a meal is consumed had an effect on which genes were differentially regulated in the acute postprandial period, with only 6.5% of differentially expressed genes the same both morning and night. More genes were involved in lipid metabolic pathways in the morning and immune pathways at night. RTqPCR analysis of target genes suggested that key regulatory genes responsible for nutrient sensing and lipid and glucose metabolism are differentially expressed at night. These may play a role in improved blood glucose control in peripheral tissues that is observed after eating in the morning but to a lesser extent or not at all at night. Modulation of the macronutrient composition of a meal led to changes in expression of genes involved in the circadian clock and metabolism. CONCLUSIONS Investigating the differences in the transcriptomic response to food at night provides a greater understanding of the mechanisms underlying the changing metabolic phenotypes, characterised by circulating metabolic biomarkers, according to the time of day.
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Tandem Mass Spectrometry as Strategy for the Selective Identification and Quantification of the Amyloid Precursor Protein Tyr682 Residue Phosphorylation Status in Human Blood Mononuclear Cells.
Reveglia, P, Nasso, R, Angiolillo, A, Lecce, L, Paolillo, C, De Tullio, S, Gelzo, M, Di Costanzo, A, Matrone, C, Corso, G
Biomolecules. 2021;(9)
Abstract
Background: Alzheimer's disease (AD) is a devastating neurodegenerative disease without guidelines for early diagnosis or personalized treatment. Previous studies have highlighted a crucial role of increasing phosphorylation levels of the amyloid precursor protein (APP) Tyr682 residue in predicting neuronal deficits in AD patients. However, the lack of a method for the identification and quantification of Tyr682 phosphorylation levels prevents its potential clinical applications. Methods: Here we report a method to identify and quantify APP Tyr682 phosphorylation levels in blood mononuclear cells of AD patients by tandem mass spectrometry (tMS). Results: This method showed excellent sensitivity with detection and quantification limits set respectively at 0.035 and 0.082 ng injected for the phosphorylated peptide and at 0.02 and 0.215 ng injected for the non-phosphorylated peptide. The average levels of both peptides were quantified in transfected HELA cells (2.48 and 3.53 ng/μg of protein, respectively). Preliminary data on 3 AD patients showed quantifiable levels of phosphorylated peptide (0.10-0.15 ng/μg of protein) and below the LOQ level of non-phosphorylated peptide (0.13 ng/μg of protein). Conclusion: This method could allow the identification of patients with increased APP Tyr682 phosphorylation and allow early characterization of molecular changes prior to the appearance of clinical signs.