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Effects of vitamin D supplementation on circulating concentrations of growth factors and immune-mediators in healthy women during pregnancy.
Khatiwada, A, Wolf, BJ, Mulligan, JK, Shary, JR, Hewison, M, Baatz, JE, Newton, DA, Hawrylowicz, C, Hollis, BW, Wagner, CL
Pediatric research. 2021;(3):554-562
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Abstract
BACKGROUND For the second aim of the Kellogg Foundation grant, this double-blind RCT investigated the impact of plasma vitamin D metabolite 25-hydroxyvitamin D (25(OH)D) on plasma immune-mediators during pregnancy. We hypothesized that higher 25(OH)D concentrations would associate with reduced pro-inflammatory and increased tolerogenic immune-mediator concentrations. METHODS Pregnant women enrolled at 10-14 weeks gestation were randomized to 400 or 4400 IU vitamin D3/day. Data on health, safety, circulating 25(OH)D, and 9 immune-mediators were collected at each trimester. Associations between immune-mediators and 25(OH)D at baseline and at second and third trimesters were examined. RESULTS Baseline TGF-β and second and third trimesters IFN-γ and IL-2 were associated with baseline 25(OH)D. Baseline immune-mediators were associated with immune-mediators at second and third trimesters for all immune-mediators except IL-5 and IL-10. Race was associated with baseline TGF-β, VEGF and IL-10 and with IL-10 at second and third trimesters. CONCLUSIONS Both treatment groups had increased 25(OH)D at second and third trimesters, greatest in the 4400 IU group. Though associations between baseline 25(OH)D and baseline TGF-β and second and third trimester IFN-γ and IL-2 were noted, vitamin D supplementation throughout pregnancy did not impact immune-mediators at later trimesters. Supplementing with vitamin D before conception conceivably influences immune-mediator responses during pregnancy. IMPACT In this vitamin D supplementation clinical trial, baseline (first trimester) but not increasing plasma 25(OH)D concentration impacted select plasma immune-mediator profiles in pregnant women. Baseline 25(OH)D was associated with baseline TGF-β and with IFN-γ and IL-2 at second and third trimesters. Baseline IFN-γ, CRP, TGF-β, TNF-α, VEGF, IL-2, and IL-4 were associated with concentrations at second and third trimesters for respective immune-mediators; however, 25(OH)D concentration at second and third trimesters were not. Some racial differences existed in immune-mediator concentrations at baseline and at second and third trimesters. This study assesses the impact of vitamin D supplementation on multiple immune-mediators in pregnant women of different racial/ethnic groups using longitudinal data from a relatively large randomized controlled trial. This study found that race was associated with baseline TGF-β, VEGF, and IL-10 and with IL-10 at second and third trimesters, a novel finding that sheds light where relationships were less well defined. The results of this study suggest that vitamin D supplementation before conception or early in pregnancy, rather than during pregnancy, may be necessary to significantly impact immune-mediator response. This study sets premise for future clinical trials to evaluate the effect of vitamin D supplementation before conception or prior to pregnancy.
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Effect of interscalene nerve block on the inflammatory response in shoulder surgery: a randomized trial.
Mejía-Terrazas, GE, Ruíz-Suárez, M, Vadillo-Ortega, F, Franco Y Bourland, RE, López-Muñoz, E
Journal of shoulder and elbow surgery. 2019;(9):e291-e303
Abstract
BACKGROUND Comparing techniques of general anesthesia and regional anesthesia in arthroscopic shoulder surgery, some studies have shown differences in the intensity of immediate postoperative pain and neuroendocrine response, but the inflammatory response when using balanced general anesthesia (BGA) vs. an ultrasound-guided (USG) single-dose interscalene block (SDIB) has not been compared. MATERIALS AND METHODS In a single-center, prospective, randomized clinical trial, the inflammatory response of 2 groups of 10 patients scheduled to undergo arthroscopic shoulder surgery was evaluated through measurement of a panel of cytokines that act on cells of the adaptive immune response to promote or inhibit inflammation, chemokines involved in chemotaxis, the erythrocyte sedimentation rate (ESR), the high-sensitivity C-reactive protein (CRP) level, and the white blood cell (WBC) count in 3 blood samples (before anesthesia, immediately postoperatively, and 24 hours postoperatively) with 2 types of anesthesia (BGA vs. USG SDIB). Postoperative pain intensity (immediately, at 12 hours, and at 24 hours) was also assessed. RESULTS The ESR and CRP level increased significantly at 24 hours after surgery; however, the increase in ESR (P < .0001) and CRP level (P < .0001) was lower in the USG SDIB group. Significant increases in the levels of soluble interleukin 2 receptor α (P = .022) and interleukin 12p40 (P = .016) occurred in the immediate postoperative period in the USG SDIB group. Immediate postoperative pain showed a significant increase (P < .001) in the BGA group. CONCLUSIONS In arthroscopic shoulder surgery, the use of a USG SDIB compared with the use of BGA is possibly associated with improved pain control in the immediate postoperative period and lower immunosuppression, even at 24 hours after surgery.
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Association of serum FAM19A5 with metabolic and vascular risk factors in human subjects with or without type 2 diabetes.
Lee, YB, Hwang, HJ, Kim, JA, Hwang, SY, Roh, E, Hong, SH, Choi, KM, Baik, SH, Yoo, HJ
Diabetes & vascular disease research. 2019;(6):530-538
Abstract
OBJECTIVES A recent experimental study revealed that family with sequence similarity 19 [chemokine (C-C motif)-like] member A5 (FAM19A5), a novel secreted adipokine, has inhibitory effects on vascular smooth muscle cell proliferation and migration, and on neointima formation in injured arteries. We investigated the associations between serum FAM19A5 concentration and cardio-metabolic risk factors for the first time in human subjects. METHODS Circulating FAM19A5 concentrations and their associations with cardio-metabolic risk factors were explored in 223 individuals (45 without diabetes and 178 with type 2 diabetes). RESULTS Serum FAM19A5 concentrations (pg/mL) were greater in patients with type 2 diabetes [median (interquartile range), 172.70 (116.19, 286.42)] compared with non-diabetic subjects [92.09 (70.32, 147.24)] (p < 0.001). Increasing serum FAM19A5 tertile was associated with trends of increasing waist-to-hip ratio, fasting plasma glucose, glycated haemoglobin and mean brachial-ankle pulse wave velocity. Serum FAM19A5 was positively correlated with waist circumference, waist-to-hip ratio, alanine aminotransferase, fasting plasma glucose, glycated haemoglobin and mean brachial-ankle pulse wave velocity. Multiple stepwise regression analyses identified waist-to-hip ratio, low-density lipoprotein cholesterol and brachial-ankle pulse wave velocity as determining factors for log-transformed serum FAM19A5 concentration (R2 = 0.0689). CONCLUSION A novel adipokine FAM19A5 was related to various metabolic and vascular risk factors in humans, suggesting its potential as a biomarker of cardio-metabolic disease.
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Omega-3 supplementation with resistance training does not improve body composition or lower biomarkers of inflammation more so than resistance training alone in older men.
Cornish, SM, Myrie, SB, Bugera, EM, Chase, JE, Turczyn, D, Pinder, M
Nutrition research (New York, N.Y.). 2018;:87-95
Abstract
The purpose of this study was to evaluate the effectiveness of 3.0 g/d of omega-3 fatty acid (eicosapentaenoic acid and docosahexaenoic acid) supplementation combined with progressive resistance training to improve body composition and lower inflammatory cytokines in older men when compared to placebo and resistance training. We hypothesized that completing a 12-week omega-3 supplementation period along with whole body resistance exercise (3 times/wk) would result in a significantly greater improvement in lean tissue mass as well as a significant decrease in interleukin-6 and tumor necrosis factor-α when compared to placebo. A total of 23 older men (≥65 years old) were randomized to an omega-3 supplementation group (n = 11) or placebo group (n = 12), and all the participants completed the same whole body progressive resistance training program. Baseline and 12-week data collection included body composition, muscle strength, functional ability, and inflammatory cytokines. Results indicated a significant main effect for time (all P < .05) for percent body fat (-2.5%), lean tissue mass (+1.1%), lumbar bone mineral density (+1.1%), hip bone mineral content (+1.1%), chest press strength (+31%), leg press strength (+37%), timed-up-and-go (-6.6%), and 6-minute walk distance (+4.5%) from baseline to post 12 weeks. No significant effects were noted for the 2 inflammatory cytokines measured (P > .05). We conclude that progressive resistance training exercise is an excellent method to enhance parameters of body composition, skeletal muscle strength, and functional ability in older men, whereas omega-3 supplementation did nothing to enhance these parameters or influence inflammatory biomarkers.
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Evaluation of irisin and visfatin levels in very low birth weight preterm newborns compared to full term newborns-A prospective cohort study.
Mól, N, Zasada, M, Tomasik, P, Klimasz, K, Kwinta, P
PloS one. 2018;(9):e0204835
Abstract
Premature infants represent one of the groups with increased risk for metabolic syndrome. Our study is the first one to evaluate irisin and visfatin levels, associated with the metabolic syndrome, both in blood of preterm and full-term infants, as well as in the breastmilk of their mothers. A total of 72 newborns was enrolled in the study, including 53 very low birth weight preterm infants and a control group of 19 term infants. The levels of irisin and visfatin were determined by a commercial enzyme-linked immunoabsorbent assay both in the baby serum and maternal milk twice, first during the 1st week of life and then 4 weeks later. Preterm infants had significantly lower serum irisin levels compared to the term infants. Overall, serum irisin level during the 1st week of life was positively correlated with several anthropometric measurements at birth, as well as during 5th weeks of age. In contrast, serum visfatin levels during 5th week of life were negatively correlated with z-scores of birth weight, weight and head circumference during 5th week of age. We found a strong negative correlation between serum irisin and serum visfatin levels at both analyzed time points. The level of milk visfatin was significantly higher in the mothers of the preterm group during 5th week of life. In conclusion, our results provide further evidence that irisin and visfatin may play physiologic roles in development of both preterm and full-term newborns during their first month after birth. Observed differences in irisin and visfatin serum and breastmilk concentrations during the earliest stages of life may contribute to development of catch up growth, but also, they might eventually lead to a higher risk for metabolic syndrome in prematurely born children in later years.
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Effect of Vegan Fecal Microbiota Transplantation on Carnitine- and Choline-Derived Trimethylamine-N-Oxide Production and Vascular Inflammation in Patients With Metabolic Syndrome.
Smits, LP, Kootte, RS, Levin, E, Prodan, A, Fuentes, S, Zoetendal, EG, Wang, Z, Levison, BS, Cleophas, MCP, Kemper, EM, et al
Journal of the American Heart Association. 2018;(7)
Abstract
BACKGROUND Intestinal microbiota have been found to be linked to cardiovascular disease via conversion of the dietary compounds choline and carnitine to the atherogenic metabolite TMAO (trimethylamine-N-oxide). Specifically, a vegan diet was associated with decreased plasma TMAO levels and nearly absent TMAO production on carnitine challenge. METHODS AND RESULTS We performed a double-blind randomized controlled pilot study in which 20 male metabolic syndrome patients were randomized to single lean vegan-donor or autologous fecal microbiota transplantation. At baseline and 2 weeks thereafter, we determined the ability to produce TMAO from d6-choline and d3-carnitine (eg, labeled and unlabeled TMAO in plasma and 24-hour urine after oral ingestion of 250 mg of both isotope-labeled precursor nutrients), and fecal samples were collected for analysis of microbiota composition. 18F-fluorodeoxyglucose positron emission tomography/computed tomography scans of the abdominal aorta, as well as ex vivo peripheral blood mononuclear cell cytokine production assays, were performed. At baseline, fecal microbiota composition differed significantly between vegans and metabolic syndrome patients. With vegan-donor fecal microbiota transplantation, intestinal microbiota composition in metabolic syndrome patients, as monitored by global fecal microbial community structure, changed toward a vegan profile in some of the patients; however, no functional effects from vegan-donor fecal microbiota transplantation were seen on TMAO production, abdominal aortic 18F-fluorodeoxyglucose uptake, or ex vivo cytokine production from peripheral blood mononuclear cells. CONCLUSIONS Single lean vegan-donor fecal microbiota transplantation in metabolic syndrome patients resulted in detectable changes in intestinal microbiota composition but failed to elicit changes in TMAO production capacity or parameters related to vascular inflammation. CLINICAL TRIAL REGISTRATION URL: http://www.trialregister.nl. Unique identifier: NTR 4338.
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The PNPLA3 I148M variant modulates the fibrogenic phenotype of human hepatic stellate cells.
Bruschi, FV, Claudel, T, Tardelli, M, Caligiuri, A, Stulnig, TM, Marra, F, Trauner, M
Hepatology (Baltimore, Md.). 2017;(6):1875-1890
Abstract
UNLABELLED The genetic polymorphism I148M of patatin-like phospholipase domain-containing 3 (PNPLA3) is robustly associated with hepatic steatosis and its progression to steatohepatitis, fibrosis, and cancer. Hepatic stellate cells (HSCs) are key players in the development of liver fibrosis, but the role of PNPLA3 and its variant I148M in this process is poorly understood. Here we analyzed the expression of PNPLA3 during human HSC activation and thereby explored how a PNPLA3 variant impacts hepatic fibrogenesis. We show that expression of PNPLA3 gene and protein increases during the early phases of activation and remains elevated in fully activated HSCs (P < 0.01). Knockdown of PNPLA3 significantly decreases the profibrogenic protein alpha-smooth muscle actin (P < 0.05). Primary human I148M HSCs displayed significantly higher expression and release of proinflammatory cytokines, such as chemokine (C-C motif) ligand 5 (P < 0.01) and granulocyte-macrophage colony-stimulating factor (P < 0.001), thus contributing to migration of immune cells (P < 0.05). Primary I148M HSCs showed reduced retinol (P < 0.001) but higher lipid droplet content (P < 0.001). In line with this, LX-2 cells stably overexpressing I148M showed augmented proliferation and migration, lower retinol, and abolished retinoid X receptor/retinoid A receptor transcriptional activities but more lipid droplets. Knockdown of I148M PNPLA3 (P < 0.001) also reduces chemokine (C-C motif) ligand 5 and collagen1α1 expression (P < 0.05). Notably, I148M cells display reduced peroxisome proliferator-activated receptor gamma transcriptional activity, and this effect was attributed to increased c-Jun N-terminal kinase, thereby inhibiting peroxisome proliferator-activated receptor gamma through serine 84 phosphorylation and promoting activator protein 1 transcription. Conversely, the c-Jun N-terminal kinase inhibitor SP600125 and the peroxisome proliferator-activated receptor gamma agonist rosiglitazone decreased activator protein 1 promoter activity. CONCLUSIONS These data indicate that PNPLA3 is required for HSC activation and that its genetic variant I148M potentiates the profibrogenic features of HSCs, providing a molecular mechanism for the higher risk of progression and severity of liver diseases conferred to patients carrying the I148M variant. (Hepatology 2017;65:1875-1890).
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Visfatin is a positive predictor of bone mineral density in young survivors of acute lymphocytic leukemia.
Siviero-Miachon, AA, Spinola-Castro, AM, de Martino Lee, ML, Calixto, AR, Geloneze, B, Lazaretti-Castro, M, Guerra-Junior, G
Journal of bone and mineral metabolism. 2017;(1):73-82
Abstract
Bone mass acquisition may be compromised in survivors of childhood acute lymphocytic leukemia due to various factors, including adiposity. Fat accumulation can affect bone through the direct effect of adipokines or indirectly through the state of chronic inflammation. The aim of this study was to evaluate the effect of body composition and adipokines on bone mass in survivors of acute lymphocytic leukemia. This was a cross-sectional study of 56 survivors aged between 15 and 24 years, 44.6 % of whom received cranial radiotherapy (18-24 Gy), assessed according to body fat, lean mass, and bone mineral density (dual energy X-ray absorptiometry), computed tomography scan-derived abdominal adipose tissue, and adipokines by a multiple regression analysis. Both lumbar spine L1-L4 (trabecular bone) and total body (cortical bone) bone mineral density were positively correlated with visfatin (p < 0.050). Lean mass index was positively correlated, while waist-to-height ratio was negatively correlated with cortical bone (p < 0.010). Low bone mineral density for chronological age was detected in 5.4 % of patients in total body, and 8.9 % at the lumbar spine. In survivors of acute lymphocytic leukemia, visfatin may play an important role in the complex relationship between body composition and bone. At present, visfatin may represent a model for further study of bone metabolism, and could possibly explain the unknown mechanisms linking bone metabolism and cancer.
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Serum Levels of Visfatin and Interleukin-6 in Non-Obese Versus Obese Men with Coronary Artery Disease.
Naz, Sh, Sandhu, QSh, Akhtar, A, Zafar, U, Khalid, A, Saeed, M
Journal of the College of Physicians and Surgeons--Pakistan : JCPSP. 2017;(2):71-74
Abstract
OBJECTIVE To evaluate and compare the serum levels of visfatin, interleukin-6 and lipid profile in non-obese and obese male patients with coronary artery disease. STUDY DESIGN Observational, comparative study. PLACE AND DURATION OF STUDY Punjab Institute of Cardiology and Lahore General Hospital, Lahore, from July to December 2013. METHODOLOGY The participants included 20 non-obese group I with coronary artery disease (CAD) and 20 obese males group II with coronary artery disease (angiographically confirmed). All the participants were in the age group of 35 - 55 years being non-smokers and non-diabetic. Serum visfatin and interleukin-6 levels were analysed by Enzyme Linked Immunosorbent Assay (ELISA). Lipid profile was also evaluated. Results were compared with T-test and Mann Whitney U test. The values were considered significant at 0.05 level of significance. RESULTS Serum visfatin 9.05 versus 3.9 ng/ml and interleukin-6 12.80 versus 0.60 pg/ml levels were significantly (p-value < 0.001 of both) raised in the obese CAD group as compared to non-obese with CAD. Lipid profile also showed raised levels of total serum cholesterol, low density lipoproteins, triglycerides, very low density lipoproteins and low levels of high density lipoproteins in obese group. CONCLUSION Significantly raised levels of serum visfatin and interleukin-6 indicate adipose tissue as an imperative source of these adipocytokines involved in inflammation in CAD. Altered lipid profile also seen in obese patients with CAD.
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Detraining-induced alterations in adipokines and cardiometabolic risk factors after nonlinear periodized resistance and aerobic interval training in obese men.
Nikseresht, M, Hafezi Ahmadi, MR, Hedayati, M
Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme. 2016;(10):1018-1025
Abstract
This study compared the effects of nonlinear resistance training (NRT), aerobic interval training (AIT), and detraining on adipokines and cardiometabolic risk factors in middle-aged obese men. Thirty-three obese men were randomly allocated to NRT (n = 12), AIT (n = 10), and control (CON, n = 11) groups. Subjects in experimental groups performed exercise protocols 3 days per week for 12 weeks followed by a 4-week detraining period. The NRT involved 55 min of weight training with flexible periodization. The AIT consisted of running on a treadmill (4 × 4-min intervals at 90% of maximal heart rate, with each interval separated by 3 min at 65%). Peak oxygen consumption increased significantly after training compared with CON (P < 0.01), but it increased more in the AIT group than in the NRT group (P = 0.004). After detraining, peak oxygen consumption decreased significantly in both training groups (P < 0.001); however, the value in the AIT group was still higher than that in the CON group (P = 0.003). No significant changes were observed in serum levels of omentin-1 and interleukin (IL)-18 after training (P > 0.05), but omentin-1 decreased significantly in both training groups and IL-18 increased significantly in the NRT group after detraining (P < 0.05). High-density lipoprotein cholesterol (HDL-C) increased significantly after training in the AIT group compared with the CON group (P < 0.05) and returned to the pre-training level after detraining. Conversely, apelin-13 increased significantly in response to training, compared with baseline (P < 0.05), and remained unchanged after detraining. Both training regimens had similar effects on most markers; however, AIT seems to have stronger anti-coronary disease effects (as indicated by HDL-C and peak oxygen consumption) than NRT.