| 1. |
- Eriksson, Anders, et al.
(författare)
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Implication of coronin 7 in body weight regulation in humans, mice and flies
- 2015
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Ingår i: BMC Neuroscience. - : Springer Science and Business Media LLC. - 1471-2202. ; 16
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Tidskriftsartikel (refereegranskat)abstract
- Background: Obesity is a growing global concern with strong associations with cardiovascular disease, cancer and type-2 diabetes. Although various genome-wide association studies have identified more than 40 genes associated with obesity, these genes cannot fully explain the heritability of obesity, suggesting there may be other contributing factors, including epigenetic effects. Results: We performed genome wide DNA methylation profiling comparing normal-weight and obese 9-13 year old children to investigate possible epigenetic changes correlated with obesity. Of note, obese children had significantly lower methylation levels at a CpG site located near coronin 7 (CORO7), which encodes a tryptophan-aspartic acid dipeptide (WD)-repeat containing protein most likely involved in Golgi complex morphology and function. Anatomical profiling of coronin 7 (Coro7) mRNA expression in mice revealed that it is highly expressed in appetite and energy balance regulating regions, including the hypothalamus, striatum and locus coeruleus, the main noradrenergic brain site. Interestingly, we found that food deprivation in mice downregulates hypothalamic Coro7 mRNA levels, and injecting ethanol, an appetite stimulant, increased the number of Coro7 expressing cells in the locus coeruleus. Finally, by employing the genetically-tractable Drosophila melanogaster model we were able to demonstrate an evolutionarily conserved metabolic function for the CORO7 homologue pod1. Knocking down the pod1 in the Drosophila adult nervous system increased their resistance to starvation. Furthermore, feeding flies a high-calorie diet significantly increased pod1 expression. Conclusion: We conclude that coronin 7 is involved in the regulation of energy homeostasis and this role stems, to some degree, from the effect on feeding for calories and reward.
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| 2. |
- Tsartsalis, Athanasios N., et al.
(författare)
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Bone Metabolism Markers in Thalassemia Major-Induced Osteoporosis: Results from a Cross-Sectional Observational Study
- 2019
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Ingår i: Current molecular medicine. - : BENTHAM SCIENCE PUBL LTD. - 1566-5240 .- 1875-5666. ; 19:5, s. 335-341
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Tidskriftsartikel (refereegranskat)abstract
- Background: Thalassemia major (TM) patients eventually face many new health conditions, including endocrinopathies and low bone mineral density, usually observed in the aging general population. Objective: The aim of the current study was to evaluate the biomarkers of bone remodeling in TM patients and to compare them with both osteoporotic and healthy population, in order to investigate the new therapeutic paths. Methods: Sixty-four patients with TM (32 men and 32 women) participated in the study. The patients were evaluated with dual-energy X-ray absorptiometry (DXA) of the lumbar spine and femoral neck and with markers of bone remodeling including receptor activator of nuclear factor kappa-B ligand (RANKL), osteoprotegerin (OPG), C-terminal telopeptide (CTX), and sclerostin. Results were compared with those from 12 postmenopausal women with osteoporosis and 12 women with normal bone mineral density. Results: The statistical analysis of the biochemical markers of bone metabolism revealed overall significant differences between the three groups only for RANKL and OPG/RANKL (p=0.049 and p=0.009). RANKL was higher and OPG/RANKL was lower in TM patients compared to osteoporosis group. Conclusion: Patients with TM do not have a higher probability of suffering from osteoporosis from the general population. However, some markers of osteoclast activity differ between patients with TM and osteoporosis, indicating the possible differences in terms of anti-osteoporotic treatment. The lack of significant differences among the three groups in regards to the levels of CTX and sclerostin may indicate the potential efficacy of the current osteoporotic treatment also for TM patients.
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| 3. |
- Tsartsalis, Athanasios N., et al.
(författare)
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The role of biphosphonates in the management of thalassemia-induced osteoporosis: a systematic review and meta-analysis
- 2018
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Ingår i: HORMONES-INTERNATIONAL JOURNAL OF ENDOCRINOLOGY AND METABOLISM. - : SPRINGER. - 1109-3099. ; 17:2, s. 153-166
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Forskningsöversikt (refereegranskat)abstract
- Thalassemia Major (TM) is a clinical entity with a high prevalence of low bone mass. The aim of the present study was to perform a meta-analysis of all available data on the role of bisphosphonates (BPs) in the therapy of thalassemia major-induced osteoporosis. The PRISMA recommendations for reporting systematic reviews and meta-analyses were used to guide the present study. We searched PubMed and the Cochrane Central Register of Controlled Trials (CENTRAL) through March 31, 2017 for articles related to thalassemia and BPs. To meta-analytically synthesize the primary endpoint, we used the standardized mean difference (SMD) after Hedgess g transformation under the scenario of a random effects model. Heterogeneity across studies was examined using the I (2) statistic. Nine randomized controlled trials (RCTs) containing original data were included in this review. Three studies were performed in Italy, one in Australia, three in Greece, one in Cyprus, and one in China. The BPs investigated included zoledronate, alendronate, pamidronate, clodronate, and neridronate. Zoledronate and alendronate showed a tendency to perform best as compared to neridronate and the placebo effect with respect to femoral neck, lumbar spine, total hip, and total body in terms of bone mass density (g/cm(2)). BPs and in particular, zolendronate, were quite effective in the treatment of osteoporosis. These findings suggested that bisphosphonates are still a front-line treatment of osteoporosis in TM. However, to draw more meaningful and significant conclusions for the use and efficacy of BP in TM, larger and more complete RCTs should be conducted.
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| 4. |
- Voisin, Sarah, et al.
(författare)
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Dietary fat quality impacts genome-wide DNA methylation patterns in a cross-sectional study of Greek preadolescents
- 2015
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Ingår i: European Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1018-4813 .- 1476-5438. ; 23, s. 654-662
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Tidskriftsartikel (refereegranskat)abstract
- The type and the amount of dietary fat have a significant influence on the metabolic pathways involved in the development of obesity, metabolic syndrome, diabetes type 2 and cardiovascular diseases. However, it is unknown to what extent this modulation is achieved through DNA methylation. We assessed the effects of cholesterol intake, the proportion of energy intake derived from fat, the ratio of polyunsaturated fatty acids (PUFA) to saturated fatty acids (SFA), the ratio of monounsaturated fatty acids (MUFA) to SFA, and the ratio of MUFA+PUFA to SFA on genome-wide DNA methylation patterns in normal-weight and obese children. We determined the genome-wide methylation profile in the blood of 69 Greek preadolescents (∼10 years old) as well as their dietary intake for two consecutive weekdays and one weekend day. The methylation levels of one CpG island shore and four sites were significantly correlated with total fat intake. The methylation levels of 2 islands, 11 island shores and 16 sites were significantly correlated with PUFA/SFA; of 9 islands, 26 island shores and 158 sites with MUFA/SFA; and of 10 islands, 40 island shores and 130 sites with (MUFA+PUFA)/SFA. We found significant gene enrichment in 34 pathways for PUFA/SFA, including the leptin pathway, and a significant enrichment in 5 pathways for (MUFA+PUFA)/SFA. Our results suggest that specific changes in DNA methylation may have an important role in the mechanisms involved in the physiological responses to different types of dietary fat.European Journal of Human Genetics advance online publication, 30 July 2014; doi:10.1038/ejhg.2014.139.
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| 5. |
- Henriksson, Hanna E., et al.
(författare)
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Blood plasma metabolic profiling of pregnant women with antenatal depressive symptoms
- 2019
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Ingår i: Translational Psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Antenatal depression affects similar to 9-19% of pregnant women and can exert persistent adverse effects on both mother and child. There is a need for a deeper understanding of antenatal depression mechanisms and the development of tools for reliable diagnosis and early identification of women at high risk. As the use of untargeted blood metabolomics in the investigation of psychiatric and neurological diseases has increased substantially, the main objective of this study was to investigate whether untargeted gas chromatography-mass spectrometry (GC-MS) plasma metabolomics in 45 women in late pregnancy, residing in Uppsala, Sweden, could indicate metabolic differences between women with and without depressive symptoms. Furthermore, seasonal differences in the metabolic profiles were explored. When comparing the profiles of cases with controls, independently of season, no differences were observed. However, seasonal differences were observed in the metabolic profiles of control samples, suggesting a favorable cardiometabolic profile in the summer vs. winter, as indicated by lower glucose and sugar acid concentrations and lactate to pyruvate ratio, and higher abundance of arginine and phosphate. Similar differences were identified between cases and controls among summer pregnancies, indicating an association between a stressed metabolism and depressive symptoms. No depression-specific differences were apparent among depressed and non-depressed women, in the winter pregnancies; this could be attributed to an already stressed metabolism due to the winter living conditions. Our results provide new insights into the pathophysiology of antenatal depression, and warrant further investigation of the use of metabolomics in antenatal depression in larger cohorts.
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| 6. |
- Iliadis, Stavros I, et al.
(författare)
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Mid-pregnancy corticotropin-releasing hormone levels in association with postpartum depressive symptoms
- 2016
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Ingår i: Depression and anxiety (Print). - : Hindawi Limited. - 1091-4269 .- 1520-6394. ; 33:11, s. 1023-1030
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Tidskriftsartikel (refereegranskat)abstract
- Background: Peripartum depression is a common cause of pregnancy and postpartum related morbidity. The production of corticotropin-releasing hormone (CRH) from the placenta alters the profile of hypothalamus-pituitary-adrenal axis hormones and may be associated with postpartum depression. The purpose of this study was to assess, in non-depressed pregnant women, the possible association between CRH levels in pregnancy and depressive symptoms postpartum.Methods: A questionnaire containing demographic data and the Edinburgh Postnatal Depression Scale was filled in gestational weeks 17 and 32, and six weeks postpartum. Blood samples were collected in week 17 for assessment of CRH. A logistic regression model was constructed, using postpartum Edinburgh Postnatal Depression Scale score as the dependent variable and log transformed CRH levels as the independent variable. Confounding factors were included in the model. Sub-analyses after exclusion of study subjects with preterm birth, small for gestational age newborns, and women on corticosteroids were performed.Results: 535 women without depressive symptoms during pregnancy were included. Logistic regression showed an association between high CRH levels in gestational week 17 and postpartum depressive symptoms, before and after controlling for several confounders (unadjusted Odds Ratio = 1.11; 95% CI 1.01 – 1.22, adjusted Odds Ratio = 1.13; 95% CI 1.02 – 1.26, per 0.1 unit increase in log corticotropin-releasing hormone). Exclusion of women with preterm birth and newborns small for gestational age as well as women who used inhalation corticosteroids during pregnancy did not alter the results.Conclusions: This study suggests an association between high CRH levels in gestational week 17 and the development of postpartum depressive symptoms, among women without depressive symptoms during pregnancy.
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| 7. |
- Papadopoulou-Marketou, Nektaria, 1974-, et al.
(författare)
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Biomarkers of diabetic nephropathy: A 2017 update
- 2017
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Ingår i: Critical reviews in clinical laboratory sciences. - : TAYLOR & FRANCIS LTD. - 1040-8363 .- 1549-781X. ; 54:5, s. 326-342
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Forskningsöversikt (refereegranskat)abstract
- Diabetic nephropathy (DN), also named diabetic kidney disease (DKD), is a devastating complication in patients with both type 1 and 2 diabetes mellitus (T1D and T2D) and its diagnosis has been traditionally based on the presence of micro-albuminuria (MA). The aim of this article is to update, through review of the relevant medical literature, the most promising biomarkers for early DKD detection. MA has historically been employed as an early marker of microvascular complications, indicating risk for advanced CKD. However, due to the inability of MA to adequately predict DKD, especially in young patients or in non-albuminuric DKD, additional biomarkers of glomerular and/or tubular injury have been proposed to uncover early renal dysfunction and structural lesions, even before MA occurs. Defining new predictive biomarkers to use alongside urinary albumin excretion (UAE) during the initial stages of DKD would provide a window of opportunity for preventive and/or therapeutic interventions to prevent or delay the onset of irreversible long-term complications and to improve outcomes by minimizing the rates of severe cardio-renal morbidity and mortality in DKD patients.
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| 8. |
- Papadopoulou-Marketou, Nektaria, 1974-, et al.
(författare)
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Diabetic nephropathy in type 1 diabetes: a review of early natural history, pathogenesis, and diagnosis
- 2017
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Ingår i: Diabetes/Metabolism Research Reviews. - : WILEY. - 1520-7552 .- 1520-7560. ; 33:2
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Forskningsöversikt (refereegranskat)abstract
- Diabetic nephropathy constitutes a devastating complication in patients with type 1 diabetes mellitus, and its diagnosis is traditionally based on microalbuminuria. The aim of this review is to update through the medical literature the suggested early natural course of diabetic nephropathy, the theories behind the pathways of its pathogenesis, and its diagnosis. Poor glycemic control, dyslipidemia, smoking, advanced glycation end products, and environmental and genetic clues play an important role in the development of diabetic nephropathy. Microalbuminuria has been traditionally considered as a primary early marker of microvascular complication unraveling the risk for progress to the advanced stages of chronic kidney disease, but because of our inability to make an early diagnosis of diabetic nephropathy in young patients as well as nonalbuminuric diabetic nephropathy, recently, other additional markers of renal injury like serum and urinary neutrophil gelatinase-associated lipocalin, chitinase-3-like protein 1, cystatin C, and plasma growth differentiation factor 15 have been proposed to unmask early renal dysfunction, even before microalbuminuria supervenes. Copyright (C) 2016 John Wiley amp; Sons, Ltd.
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| 9. |
- Papadopoulou-Marketou, Nektraria, et al.
(författare)
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NGAL and cystatin C: two possible early markers of diabetic nephropathy in young patients with type 1 diabetes mellitus: one year follow up
- 2015
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Ingår i: HORMONES-INTERNATIONAL JOURNAL OF ENDOCRINOLOGY AND METABOLISM. - : HELLENIC ENDOCRINE SOC. - 1109-3099. ; 14:2, s. 232-240
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Diabetic nephropathy constitutes a major long-term complication in patients with type 1 diabetes mellitus (T1D) and its diagnosis is based on microalbuminuria. The aim of this observational follow-up study was to explore the role of neutrophil-gelatinase-associated lipocalin (NGAL) and cystatin C in unravelling early diabetic nephropathy even in patients with normoalbuminuria.DESIGN: Fifty-six euthyroid patients with T1D, with mean age 13.1 (SD: 3.2) years, and 49 healthy controls with mean age 12.8 (SD: 6.6) were recruited. Besides standard blood chemistry and urinary albumin excretion, serum NGAL (ELISA) and cystatin C (nephelometry) were measured at enrollment and after 12-15 months. GFR was calculated with the bedside Schwartz formula (eGFR) and the Lund strategy formula (L-eGFR).RESULTS: At baseline, mean NGAL levels were not significantly different between children with diabetes and controls. At re-evaluation, mean NGAL value and mean eGFR value in patients with diabetes were increased (p=0.032 and p=0.003 respectively). At both baseline and reevaluation, NGAL was positively correlated with cystatin C (r=0.41, pless than0.001), systolic arterial pressure z-score (r=0.3, p=0.031) and creatinine (r=0.32, p=0.010). NGAL correlated negatively with eGFR (r=-0.26, p=0.049) and L-eGFR (r=-0.33, p=0.010). Cystatin C had a negative correlation to eGFR (r=-0.29, p=0.025) and a positive one with creatinine (r=0.35, p=0.009) at reevaluation. No statistically significant correlation was found between cystatin C and microalbuminuria (p=0.736).CONCLUSIONS: NGAL and cystatin C, known markers of renal injury, correlate with renal function decline in T1D, suggesting that they may be used as supplementary tests to urine albumin excretion in order to unmask early renal dysfunction.
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| 10. |
- Papadopoulou-Marketou, Nektaria, 1974-, et al.
(författare)
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NGAL as an Early Predictive Marker of Diabetic Nephropathy in Children and Young Adults with Type 1 Diabetes Mellitus
- 2017
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Ingår i: Journal of Diabetes Research. - : Hindawi Publishing Corporation. - 2314-6745 .- 2314-6753. ; 2017
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: Type 1 diabetes (T1D) is often associated with early microvascular complications. Previous studies demonstrated that increased systolic (SAP) and diastolic arterial blood pressures (DAP) are linked to microvascular morbidity in T1D. The aim of the study was to investigate the predictive role of neutrophil gelatinase-associated lipocalin (NGAL) in unravelling early cardio-renal dysfunction in T1D.METHODS: Two T1D patient groups participating in two-centre prospective cohorts were studied. Group A consisted of 57 participants aged 13.9 years (SD: 3.1) and group B consisted of 59 patients aged 28.0 years (SD: 4.4). Forty-nine healthy children [age: 10.5 years (SD: 6.6)] and 18 healthy adults [age 27.7 years (SD: 4.2)] served as controls. Serum concentrations of NGAL (ELISA) were determined, and SAP and DAP were examined (SAP and DAP also expressed as z-scores in the younger group). RESULTS: NGAL correlated positively with SAP in both patient groups (P = 0.020 and P = 0.031, resp.) and SAP z-score (P = 0.009) (group A) and negatively with eGFR in both groups (P < 0.001 and P < 0.001, resp.).CONCLUSIONS: NGAL may be proposed as a biomarker of early renal dysfunction even in nonalbuminuric T1D patients, since it was strongly associated with renal function decline and increasing systolic arterial pressure even at prehypertensive range in people with T1D, in a broad age range.
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