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1.
Calcium-phosphate homeostasis in secondary progressive multiple sclerosis patients during mitoxantrone therapy.
Lis, M, Niedziela, N, Nowak-Kiczmer, M, Kubicka-Bączyk, K, Adamczyk-Sowa, M
Neurological research. 2021;(12):1050-1055
Abstract
OBJECTIVES To assess calcium-phosphate parameters in SPMS patients treated with mitoxantrone (MTX). METHODS Thirty eight SPMS patients eligible for MTX therapy in the Department of Neurology in Zabrze, Poland were enrolled in a prospective study from March 2016 to November 2019. The parameters of serum calcium-phosphate metabolism and the neurological status according to the Expanded Disability Status Scale (EDSS) were assessed. In patients with hypovitaminosis D, vitamin D (VitD) supplementation was introduced (4000 IU/day for 1 month and later 2000 IU /day). RESULTS Most patients were women [57.89%]. The mean age [years] was 56.11 (±7.74). The median time from diagnosis to inclusion day (ID) was 7.50 [4.00-14.00] [years]. Due to VitD supplementation, an increase in serum VitD was observed during the study. 84.21% of patients presented with hypovitaminosis D before MTX treatment compared to 47.37% after treatment. Before MTX therapy, none of the patients underwent surgical repair of the fracture compared to 42.11% of patients after MTX treatment (p < 0.01). DISCUSSION Deficiency of VitD was observed at the baseline in most SPMS patients eligible for MTX therapy. Due to adverse reactions to MTX treatment, this therapy requires patient compliance, cautious drug administration and monitoring during the therapy.
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2.
Hepatic transcriptomic signatures of statin treatment are associated with impaired glucose homeostasis in severely obese patients.
Margerie, D, Lefebvre, P, Raverdy, V, Schwahn, U, Ruetten, H, Larsen, P, Duhamel, A, Labreuche, J, Thuillier, D, Derudas, B, et al
BMC medical genomics. 2019;(1):80
Abstract
BACKGROUND Clinical data identified an association between the use of HMG-CoA reductase inhibitors (statins) and incident diabetes in patients with underlying diabetes risk factors such as obesity, hypertension and dyslipidemia. The molecular mechanisms however are unknown. METHODS An observational cross-sectional study included 910 severely obese patients, mean (SD) body mass index (BMI) 46.7 (8.7), treated with or without statins (ABOS cohort: a biological atlas of severe obesity). Data and sample collection took place in France between 2006 and 2016. Transcriptomic signatures of statin treatment in human liver obtained from genome-wide transcriptomic profiling of five different statin drugs using microarrays were correlated to clinico-biological phenotypes and also assigned to biological pathways and mechanisms. Patients from the non-statin-users group were matched to patients in the statin users group by propensity score analysis to minimize confounding effects from age, gender, parental familial history of diabetes, BMI, waist circumference, systolic and diastolic blood pressure and use of anti-hypertensive drugs as pre-specified covariates. RESULTS We determined the hepatic, statin-related gene signature from genome-wide transcriptomic profiling in severely obese patients with varying degrees of glucose tolerance and cardio-metabolic comorbidities. One hundred and fifty seven patients on statin treatment in the matched cohort showed higher diabetes prevalence (OR = 2.67; 95%CI, 1.60-4.45; P = 0.0002) and impairment of glucose homeostasis. This phenotype was associated with molecular signatures of increased hepatic de novo lipogenesis (DNL) via activation of sterol regulatory element-binding protein 1 (SREBP1) and concomitant upregulation of the expression of key genes in both fatty acid and triglyceride metabolism. CONCLUSIONS A DNL gene activation profile in response to statins is associated with insulin resistance and the diabetic status of the patients. Identified molecular signatures thus suggest that statin treatment increases the risk for diabetes in humans at least in part via induction of DNL. TRIAL REGISTRATION NCT01129297 . Registered May 242,010 (retrospectively registered).
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3.
Magnesium transport and homeostasis-related gene expression in skeletal muscle of young and old adults: analysis of the transcriptomic data from the PROOF cohort Study.
Coudy-Gandilhon, C, Gueugneau, M, Taillandier, D, Combaret, L, Polge, C, Roche, F, Barthélémy, JC, Féasson, L, Maier, JA, Mazur, A, et al
Magnesium research. 2019;(3):72-82
Abstract
Magnesium (Mg2+) is critical for a number of biological processes and 25% body Mg2+ is located in the skeletal muscle. Mg2+ transport and homeostasis systems (MgTHs) regulate intracellular Mg2+ concentration and muscle MgTHs are thus related to whole body Mg2+ homeostasis. Nonetheless, few studies have investigated the regulation of muscle MgTHs under (patho)physiological conditions. Herein, we assessed the relationship between the expression of MgTHs genes (Trpm6, Trpm7, Magt1, Mrs2, Cnnm1-4, Slc41a1-3) and relevant pathways in human sarcopenia, which is one of the most dramatic physiologic changes affecting the human body. Transcriptomic data were compared between young adult (YO, 22 y, n = 11) and old (EL, 73 y, n = 13) men from the PROOF cohort. MgTH mRNA levels did not change with aging, with the exception of a slight decrease for Slc41a3. Nevertheless, interindividual variations of mRNA levels revealed strong correlations between MgTHs in the YO group, while few were maintained in the EL muscle. Moreover, in the YO muscle, different clusters of MgTH mRNAs strongly correlated with divers physiological (BMI, blood pressure) and muscle characteristics (intramyocellular droplets, capillarization); however, most correlations changed or disappeared in the EL muscle. Further investigations of the whole transcriptome identified several sets of mRNAs correlated with defined MgTHs. There again was a sharp difference between YO and EL muscles, as the number of mRNAs correlated with MgTHs strongly decreased with aging. Gene ontology analyses of these sets of correlated mRNAs revealed 6 biological processes common to YO and EL, 3 specific to the YO (RNA processing, translation, respiration), and 2 (regulation of catabolic process, Wnt signaling) to the EL muscle. Overall, these observations lead to questions about potential resilience to muscle Mg2+ homeostasis in the elderly.
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4.
H. pylori eradication with antibiotic treatment causes changes in glucose homeostasis related to modifications in the gut microbiota.
Martín-Núñez, GM, Cornejo-Pareja, I, Coin-Aragüez, L, Roca-Rodríguez, MDM, Muñoz-Garach, A, Clemente-Postigo, M, Cardona, F, Moreno-Indias, I, Tinahones, FJ
PloS one. 2019;(3):e0213548
Abstract
BACKGROUND H. pylori infection and eradication cause perturbations of the gut microbiome. The gut microbiota has been identified as a potential contributor to metabolic diseases. We evaluate whether these alterations in intestinal microbiota composition produced by H. pylori infection and its posterior eradication with antibiotic treatment could be associated with glucose homeostasis in metabolically healthy subjects. METHODS Forty adult patients infected with H. pylori and 20 control subjects were recruited. The infected subjects were evaluated before and two months after eradication treatment (omeprazole, clarithromycin, amoxicillin). The microbiota composition in fecal samples was determined by 16S rRNA gene (V3-V4) sequencing using Illumina Miseq. RESULTS Patients (pre- and post-H. pylori eradication) showed a decreased bacterial richness and diversity with respect to controls. There was an improvement in glucose homeostasis in subjects two months after H. pylori eradication treatment. Changes in the amount of Rikenellaceae, Butyricimonas, E. biforme, B. fragilis, and Megamonas were inversely associated with changes in the glucose level or related parameters (Hb1ac) in H. pylori eradication subjects. CONCLUSIONS H. pylori infection and eradication with antibiotic treatment causes alteration of the human gut microbiome. The increase in SCFA-producing bacteria and glucose-removing bacteria, specifically members of Megamonas, Rikenellaceae and Butyricimonas, has been related with an improvement in glucose homeostasis after H. pylori eradication with antibiotic treatment.
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5.
Vitamin D supplementation does not improve plasma thiol/disulfide homeostasis.
Mertoglu, C, Siranli, G, Topal, I, Gok, G, Erel, O
Pediatrics international : official journal of the Japan Pediatric Society. 2018;(11):1008-1013
Abstract
BACKGROUND Impairment of thiol/disulfide homeostasis, as well as vitamin D deficiency, are responsible for the pathophysiology of many acute and chronic diseases. This study examined the relationship between thiol/disulfide homeostasis and vitamin D level and supplementation. METHODS A total of 203 healthy children were included in the study. The participants were divided into four groups according to 25-hydroxyvitamin D (25(OH)D) level: group 1, severe deficiency (<10 ng/mL); group 2, deficiency (10-20 ng/mL); group 3, insufficiency (20-30 ng/mL); and group 4, sufficiency (≥30 ng/mL). Furthermore, group 5 was defined as being on vitamin D supplementation. RESULT Native thiol was lower in group 5 than in groups 2-4 (P = 0.003). Disulfide was higher in groups 1, 4 and 5 than groups 2 and 3 (P < 0.001). Total thiol was lower in group 5 than in group 4 (P = 0.032). The ratio of native thiol/total thiol was lower in groups 1 and 5 compared with groups 2 and 3, and in group 4 compared with group 3 (P < 0.001). The ratios of disulfide/total thiol and disulfide/native thiol were higher in groups 1 and 5 than in groups 2 and 3 whereas only the disulfide/total thiol ratio was higher in group 4 than in group 3 (P < 0.001). CONCLUSIONS In healthy children, severe deficiency of vitamin D causes impairment of thiol/disulfide homeostasis and increases protein oxidation, which cannot be reversed by external vitamin D supplementation.
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6.
Dynamic thiol/disulphide homeostasis in acute pancreatitis.
Köseoğlu, H, Alışık, M, Başaran, M, Tayfur Yürekli, Ö, Solakoğlu, T, Tahtacı, M, Ersoy, O, Erel, Ö
The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology. 2018;(3):348-353
Abstract
BACKGROUND/AIMS: The dynamic thiol/disulfide homeostasis plays pivotal roles in many physiological mechanisms in an organism. We aimed to investigate whether dynamic thiol/disulfide homeostasis changes among patients with acute pancreatitis. MATERIALS AND METHODS This prospective trial contained 45 patients with acute pancreatitis and 45 sex-and age-matched healthy volunteers as control group. Thiol/disulfide homeostasis parameters were measured by a novel and automated assay, and detected results were compared between the two groups. RESULTS Disulfide/total thiol percent ratio and disulfide/native thiol percent ratios were significantly higher in acute pancreatitis group; besides the native thiol, total thiol levels and native thiol/total thiol percent ratios were significantly lower (for all p < 0.001). CONCLUSION The thiol/disulfide homeostasis is impaired in acute pancreatitis with a shift toward the oxidative status, and this deficiency might be a pathogenic factor in acute pancreatitis. The correction of this thiol/disulfide imbalance may be a new target in the management of acute pancreatitis.
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7.
Markers of metabolic health in children differ between weekdays--the result of unhealthier weekend behavior.
Hjorth, MF, Damsgaard, CT, Michaelsen, KF, Astrup, A, Sjödin, A
Obesity (Silver Spring, Md.). 2015;(4):733-6
Abstract
OBJECTIVE The aim of this study was to investigate whether indicators of metabolic health fluctuate during the week in a group of children posing unhealthier physical activity, sedentary time, and sleep during weekends compared to weekdays. METHODS A total of 807 eight- to eleven-year-old children had valid metabolic health markers from one, two, or three measurements contributing 2190 to 2240 observations of metabolic health markers. The weekly variation was tested using linear mixed models. RESULTS Homeostatic model assessment of insulin resistance (HOMAIR), triglycerides, leptin (all P < 0.001), and adiponectin (P = 0.03) decreased from Monday to Friday, whereas ghrelin increased (P < 0.001). HOMAIR , triglycerides, and leptin were 35%, 28%, and 33% higher on Mondays compared to Fridays, respectively, and ghrelin was 7% lower on Mondays compared to Fridays (all P < 0.001). CONCLUSIONS The large weekly variation in HOMAIR , triglycerides, and leptin was likely the result of unhealthier behaviors during weekends. These findings have public health relevance and raise methodological issues that should ideally be taken into account in future studies.
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8.
Integration of Peripheral and Glandular Regulation of Triiodothyronine Production by Thyrotropin in Untreated and Thyroxine-Treated Subjects.
Hoermann, R, Midgley, JE, Larisch, R, Dietrich, JW
Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme. 2015;(9):674-80
Abstract
The objective of the study was to evaluate the roles of central and peripheral T3 regulation. In a prospective study involving 1,796 patients, the equilibria between FT3 and TSH were compared in untreated and L-T4-treated patients with varying functional states, residual thyroid secretory capacities and magnitudes of TSH stimulation. T3 concentrations were stable over wide variations in TSH levels (from 0.2 to 7 mU/l) and endogenous T4 production in untreated patients, but unbalanced in L-T4-treated athyreotic patients where T3 correlated with exogenous T4 supply. T3 stability was related to TSH-stimulated deiodinase activity by clinical observation, as predicted by theoretical modelling. Deiodinase activity in treated patients was reduced due to both diminished responsiveness to TSH and lack of thyroidal capacity. Deiodinase activity was increased in high thyroid volume, compared to lower volumes in euthyroid patients (<5 ml, p<0.001). While deiodinase differed between euthyroid and subclinically hypothyroid patients in high volume, 26.7 nmol/s (23.6, 29.2), n=214 vs. 28.9 nmol/s (26.7, 31.5), n=20, p=0.02, it was equivalent between the 2 functional groups in low volume, 23.3 nmol/s (21.3, 26.1), n=117 vs. 24.6 nmol/s (22.2, 27.5), n=38, p=0.22. These findings suggest that the thyroid gland and peripheral tissues are integrated in the physiological process of T3 homeostasis in humans via a feed-forward TSH motif, which coordinates peripheral and central regulatory mechanisms. Regulatory and capacity deficiencies collectively impair T3 homeostasis in L-T4-treated patients.
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9.
Quantifying phenotypic flexibility as the response to a high-fat challenge test in different states of metabolic health.
Kardinaal, AF, van Erk, MJ, Dutman, AE, Stroeve, JH, van de Steeg, E, Bijlsma, S, Kooistra, T, van Ommen, B, Wopereis, S
FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2015;(11):4600-13
Abstract
Metabolism maintains homeostasis at chronic hypercaloric conditions, activating postprandial response mechanisms, which come at the cost of adaptation processes such as energy storage, eventually with negative health consequences. This study quantified the metabolic adaptation capacity by studying challenge response curves. After a high-fat challenge, the 8 h response curves of 61 biomarkers related to adipose tissue mass and function, systemic stress, metabolic flexibility, vascular health, and glucose metabolism was compared between 3 metabolic health stages: 10 healthy men, before and after 4 wk of high-fat, high-calorie diet (1300 kcal/d extra), and 9 men with metabolic syndrome (MetS). The MetS subjects had increased fasting concentrations of biomarkers representing the 3 core processes, glucose, TG, and inflammation control, and the challenge response curves of most biomarkers were altered. After the 4 wk hypercaloric dietary intervention, these 3 processes were not changed, as compared with the preintervention state in the healthy subjects, whereas the challenge response curves of almost all endocrine, metabolic, and inflammatory processes regulating these core processes were altered, demonstrating major molecular physiologic efforts to maintain homeostasis. This study thus demonstrates that change in challenge response is a more sensitive biomarker of metabolic resilience than are changes in fasting concentrations.
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10.
Restoration of regulatory and effector T cell balance and B cell homeostasis in systemic lupus erythematosus patients through vitamin D supplementation.
Terrier, B, Derian, N, Schoindre, Y, Chaara, W, Geri, G, Zahr, N, Mariampillai, K, Rosenzwajg, M, Carpentier, W, Musset, L, et al
Arthritis research & therapy. 2012;(5):R221
Abstract
INTRODUCTION Systemic lupus erythematosus (SLE) is a T and B cell-dependent autoimmune disease characterized by the appearance of autoantibodies, a global regulatory T cells (Tregs) depletion and an increase in Th17 cells. Recent studies have shown the multifaceted immunomodulatory effects of vitamin D, notably the expansion of Tregs and the decrease of Th1 and Th17 cells. A significant correlation between higher disease activity and lower serum 25-hydroxyvitamin D levels [25(OH)D] was also shown. METHODS In this prospective study, we evaluated the safety and the immunological effects of vitamin D supplementation (100,000 IU of cholecalciferol per week for 4 weeks, followed by 100,000 IU of cholecalciferol per month for 6 months.) in 20 SLE patients with hypovitaminosis D. RESULTS Serum 25(OH)D levels dramatically increased under vitamin D supplementation from 18.7±6.7 at day 0 to 51.4±14.1 (p<0.001) at 2 months and 41.5±10.1 ng/mL (p<0.001) at 6 months. Vitamin D was well tolerated and induced a preferential increase of naïve CD4+ T cells, an increase of regulatory T cells and a decrease of effector Th1 and Th17 cells. Vitamin D also induced a decrease of memory B cells and anti-DNA antibodies. No modification of the prednisone dosage or initiation of new immunosuppressant agents was needed in all patients. We did not observe SLE flare during the 6 months follow-up period. CONCLUSIONS This preliminary study suggests the beneficial role of vitamin D in SLE patients and needs to be confirmed in randomized controlled trials.