Search Results
You are looking at 101 - 110 of 546 items for
- Abstract: Aging x
- Abstract: Inflammation x
- Abstract: Cognition x
Search for other papers by Charissa van Zwol-Janssens in
Google Scholar
PubMed
Search for other papers by Aglaia Hage in
Google Scholar
PubMed
Search for other papers by Kim van der Ham in
Google Scholar
PubMed
Search for other papers by Birgitta K Velthuis in
Google Scholar
PubMed
Search for other papers by Ricardo P J Budde in
Google Scholar
PubMed
Search for other papers by Maria P H Koster in
Google Scholar
PubMed
Search for other papers by Arie Franx in
Google Scholar
PubMed
Search for other papers by Bart C J M Fauser in
Google Scholar
PubMed
Search for other papers by Eric Boersma in
Google Scholar
PubMed
Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands
Search for other papers by Daniel Bos in
Google Scholar
PubMed
Search for other papers by Joop S E Laven in
Google Scholar
PubMed
Search for other papers by Yvonne V Louwers in
Google Scholar
PubMed
Search for other papers by the CREW consortium in
Google Scholar
PubMed
Besides age, estrogen exposure plays a crucial role in changes in bone density (BD) in women. Premature ovarian insufficiency (POI) and polycystic ovary syndrome (PCOS) are conditions in reproductive-aged women in which the exposure to estrogen is substantially different. Women with a history of preeclampsia (PE) are expected to have normal estrogen exposure. Within the CREw-IMAGO study, we investigated if trabecular BD is different in these women because of differences in the duration of estrogen exposure. Trabecular BD was measured in thoracic vertebrae on coronary CT scans. Women with a reduced estrogen exposure (POI) have a lower BD compared to women with an intermediate exposure (PE) (mean difference (MD) −26.8, 95% CI −37.2 to −16.3). Women with a prolonged estrogen exposure (PCOS) have the highest BD (MD 15.0, 95% CI 4.3–25.7). These results support the hypothesis that the duration of estrogen exposure in these women is associated with trabecular BD.
Significance statement
Our results suggest that middle-aged women with PCOS have a higher BD and women with POI have a lower BD. We hypothesized that this is due to either a prolonged estrogen exposure, as seen in women with PCOS, or a reduced estrogen exposure, as in women with POI. In the counseling of women with reproductive disorders on long-term health issues, coronary CT provides a unique opportunity to assess both coronary artery calcium score for cardiovascular screening as well as trabecular BD.
Search for other papers by R H M Dykgraaf in
Google Scholar
PubMed
Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
Search for other papers by S Schalekamp-Timmermans in
Google Scholar
PubMed
Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
Search for other papers by M C Adank in
Google Scholar
PubMed
Department of Internal Medicine, Academic Center for Thyroid Diseases, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
Search for other papers by S A A van den Berg in
Google Scholar
PubMed
Department of Internal Medicine, Academic Center for Thyroid Diseases, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
Search for other papers by B M N van de Lang-Born in
Google Scholar
PubMed
Search for other papers by T I M Korevaar in
Google Scholar
PubMed
Search for other papers by A Kumar in
Google Scholar
PubMed
Search for other papers by B Kalra in
Google Scholar
PubMed
Search for other papers by G V Savjani in
Google Scholar
PubMed
Division of Obstetrics and Fetal Medicine, Department of Obstetrics and Gynecology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
Search for other papers by E A P Steegers in
Google Scholar
PubMed
Search for other papers by Y V Louwers in
Google Scholar
PubMed
Search for other papers by J S E Laven in
Google Scholar
PubMed
Objective
The primary objective of this study is to establish maternal reference values of anti‐Müllerian hormone (AMH) in a fertile multi-ethnic urban pregnant population and to evaluate the effect of gestational age. The secondary objective of this study is to explore the association between AMH and placental biomarkers.
Design
This study was embedded in the Generation R Study, an ongoing population-based prospective cohort study from early pregnancy onwards.
Setting
City of Rotterdam, the Netherlands, out of hospital setting.
Patients
In 5806 women, serum AMH levels were determined in early pregnancy (median 13.5 weeks; 95% range 10.5–17.2).
Intervention(s)
None.
Main outcome measures
Maternal AMH levels in early pregnancy and its association with placental biomarkers, including human chorionic gonadotrophin (hCG), soluble fms-like tyrosine kinase-1 (sFLT), and placental growth factor (PLGF).
Results
A nomogram of AMH in early pregnancy was developed. Serum AMH levels showed a decline with advancing gestational age. Higher AMH levels were associated with a higher level of the placental biomarkers hCG and sFLT in early pregnancy. This last association was predominantly mediated by hCG. AMH levels were negatively associated with PLGF levels.
Conclusion
In this large study, we show that AMH levels in early pregnancy decrease with advancing gestational age. The association between AMH and the placental biomarkers hCG, sFLT, and PLGF suggests a better placental development with lower vascular resistance in mothers with higher AMH levels. Hence, AMH might be useful in predicting adverse pregnancy outcomes due to impaired placental development.
Search for other papers by Xu-Feng Chen in
Google Scholar
PubMed
Search for other papers by Cong He in
Google Scholar
PubMed
Search for other papers by Peng-Cheng Yu in
Google Scholar
PubMed
Search for other papers by Wei-Dong Ye in
Google Scholar
PubMed
Search for other papers by Peizhen Han in
Google Scholar
PubMed
Search for other papers by Jia-Qian Hu in
Google Scholar
PubMed
Search for other papers by Yulong Wang in
Google Scholar
PubMed
Next-generation sequencing (NGS) is of great benefit to clinical practice in terms of identifying genetic alterations. This study aims to clarify the gene background and its influence on thyroid tumor in Chinese population. NGS data and corresponding clinicopathological features (sex, age, tumor size, extrathyroidal invasion, metastasis, multifocality and TNM stage) were collected and analyzed retrospectively from 2844 individual thyroid tumor samples during July 2021 to August 2022. 2337 (82%) of the cohort possess genetic alterations including BRAF (71%), RAS (4%), RET/PTC (4%), TERT (3%), RET (2.2%) and TP53 (1.4%). Diagnostic sensitivity before surgery can be significantly increased from 0.76 to 0.91 when cytology is supplemented by NGS. Our results show that BRAF positive papillary thyroid cancer (PTC) patients tend to have elder age, smaller tumor size, less vascular invasion, more frequent tumor multifocality and significantly higher cervical lymph node metastatic rate. Mutation at RET gene codon 918 and 634 is strongly correlated with medullary thyroid cancer (MTC), However it did not display more invasive clinical characteristics. TERT positive patients are more likely to have elder age, larger tumor size, more tumor invasiveness, and more advanced TNM stage, indicating poor prognosis. Patients with TERT, RET/PTC1 and CHEK2 mutation are more susceptible to lateral lymph node metastasis. In conclusion. NGS can be a useful tool which provides practical gene evidence in the process of diagnosis and treatment in thyroid tumors.
Search for other papers by Peter Ergang in
Google Scholar
PubMed
Search for other papers by Anna Mikulecká in
Google Scholar
PubMed
Department of Physiology, Faculty of Science, Charles University, Prague, Czech Republic
Search for other papers by Martin Vodicˇka in
Google Scholar
PubMed
Search for other papers by Karla Vagnerová in
Google Scholar
PubMed
Search for other papers by Ivan Mikšík in
Google Scholar
PubMed
Department of Physiology, Faculty of Science, Charles University, Prague, Czech Republic
Search for other papers by Jirˇí Pácha in
Google Scholar
PubMed
Stress is an important risk factors for human diseases. It activates the hypothalamic–pituitary–adrenal (HPA) axis and increases plasma glucocorticoids, which are powerful regulators of immune system. The response of the target cells to glucocorticoids depends not only on the plasma concentrations of cortisol and corticosterone but also on their local metabolism. This metabolism is catalyzed by 11β-hydroxysteroid dehydrogenases type 1 and 2, which interconvert glucocorticoid hormones cortisol and corticosterone and their 11-oxo metabolites cortisone and 11-dehydrocorticosterone. The goal of this study was to determine whether stress modulates glucocorticoid metabolism within lymphoid organs – the structures where immune cells undergo development and activation. Using the resident-intruder paradigm, we studied the effect of social stress on glucocorticoid metabolism in primary and secondary lymphoid organs of Fisher 344 (F344) and Lewis (LEW) rats, which exhibit marked differences in their HPA axis response to social stressors and inflammation. We show that repeated social defeat increased the regeneration of corticosterone from 11-dehydrocorticosterone in the thymus, spleen and mesenteric lymphatic nodes (MLN). Compared with the F344 strain, LEW rats showed higher corticosterone regeneration in splenocytes of unstressed rats and in thymic and MLN mobile cells after stress but corticosterone regeneration in the stroma of all lymphoid organs was similar in both strains. Inactivation of corticosterone to 11-dehydrocorticosterone was found only in the stroma of lymphoid organs but not in mobile lymphoid cells and was not upregulated by stress. Together, our findings demonstrate the tissue- and strain-dependent regeneration of glucocorticoids following social stress.
Search for other papers by T P McVeigh in
Google Scholar
PubMed
Search for other papers by R J Mulligan in
Google Scholar
PubMed
Search for other papers by U M McVeigh in
Google Scholar
PubMed
Search for other papers by P W Owens in
Google Scholar
PubMed
Search for other papers by N Miller in
Google Scholar
PubMed
Search for other papers by M Bell in
Google Scholar
PubMed
Aix-Marseille Université, Faculté de Médecine, Marseille, France
Search for other papers by F Sebag in
Google Scholar
PubMed
Aix-Marseille Université, Faculté de Médecine, Marseille, France
Search for other papers by C Guerin in
Google Scholar
PubMed
Search for other papers by D S Quill in
Google Scholar
PubMed
Search for other papers by J B Weidhaas in
Google Scholar
PubMed
Search for other papers by M J Kerin in
Google Scholar
PubMed
Search for other papers by A J Lowery in
Google Scholar
PubMed
Introduction
MicroRNAs (miRNAs) are small noncoding RNA molecules that exert post-transcriptional effects on gene expression by binding with cis-regulatory regions in target messenger RNA (mRNA). Polymorphisms in genes encoding miRNAs or in miRNA–mRNA binding sites confer deleterious epigenetic effects on cancer risk. miR-146a has a role in inflammation and may have a role as a tumour suppressor. The polymorphism rs2910164 in the MIR146A gene encoding pre-miR-146a has been implicated in several inflammatory pathologies, including cancers of the breast and thyroid, although evidence for the associations has been conflicting in different populations. We aimed to further investigate the association of this variant with these two cancers in an Irish cohort.
Methods
The study group comprised patients with breast cancer (BC), patients with differentiated thyroid cancer (DTC) and unaffected controls. Germline DNA was extracted from blood or from saliva collected using the DNA Genotek Oragene 575 collection kit, using crystallisation precipitation, and genotyped using TaqMan-based PCR. Data were analysed using SPSS, v22.
Results
The total study group included 1516 participants. This comprised 1386 Irish participants; 724 unaffected individuals (controls), 523 patients with breast cancer (BC), 136 patients with differentiated thyroid cancer (DTC) and three patients with dual primary breast and thyroid cancer. An additional cohort of 130 patients with DTC from the South of France was also genotyped for the variant. The variant was detected with a minor allele frequency (MAF) of 0.19 in controls, 0.22 in BC and 0.27 and 0.26 in DTC cases from Ireland and France, respectively. The variant was not significantly associated with BC (per allele odds ratio = 1.20 (0.98–1.46), P = 0.07), but was associated with DTC in Irish patients (per allele OR = 1.59 (1.18–2.14), P = 0.002).
Conclusion
The rs2910164 variant in MIR146A is significantly associated with DTC, but is not significantly associated with BC in this cohort.
Search for other papers by Eva Novoa in
Google Scholar
PubMed
Search for other papers by Marcel Gärtner in
Google Scholar
PubMed
Search for other papers by Christoph Henzen in
Google Scholar
PubMed
Objective
The study aimed to assess the possible systemic effects of intratympanic dexamethasone (IT-Dex) on the hypothalamic–pituitary–adrenal (HPA) axis, inflammation, and bone metabolism.
Design
A prospective cohort study including 30 adult patients of a tertiary referral ENT clinic treated with 9.6 mg IT-Dex over a period of 10 days was carried out.
Methods
Effects on plasma and salivary cortisol concentrations (basal and after low-dose (1 μg) ACTH stimulation), peripheral white blood cell count, and biomarkers for bone turnover were measured before (day 0) and after IT-Dex (day 16). Additional measurements for bone turnover were performed 5 months after therapy. Clinical information and medication with possible dexamethasone interaction were recorded.
Results
IT-Dex was well tolerated, and no effect was detected on the HPA axis (stimulated plasma and salivary cortisol concentration on day 0: 758±184 and 44.5±22.0 nmol/l; day 16: 718±154 and 39.8±12.4 nmol/l; P=0.58 and 0.24 respectively). Concentrations of osteocalcin (OC) and bone-specific alkaline phosphatase (BSAP) did not differ after dexamethasone (OC on days 0 and 16 respectively: 24.1±10.5 and 23.6±8.8 μg/l; BSAP on day 0, 16, and after 5 months respectively: 11.5±4.2, 10.3±3.4, and 12.6±5.06 μg/l); similarly, there was no difference in the peripheral white blood cell count (5.7×1012/l and 6.1×1012/l on days 0 and 16 respectively).
Conclusions
IT-Dex therapy did not interfere with endogenous cortisol secretion or bone metabolism.
Search for other papers by Chun-feng Lu in
Google Scholar
PubMed
Search for other papers by Xiao-qin Ge in
Google Scholar
PubMed
Search for other papers by Yan Wang in
Google Scholar
PubMed
Search for other papers by Jian-bin Su in
Google Scholar
PubMed
Search for other papers by Xue-qin Wang in
Google Scholar
PubMed
Search for other papers by Dong-mei Zhang in
Google Scholar
PubMed
Search for other papers by Feng Xu in
Google Scholar
PubMed
Search for other papers by Wang-shu Liu in
Google Scholar
PubMed
Search for other papers by Min Su in
Google Scholar
PubMed
Background
Prolonged heart rate-corrected QT (QTc) interval may reflect poor prognosis of patients with type 2 diabetes (T2D). Serum adenosine deaminase (ADA) levels are related to hyperglycemia, insulin resistance (IR) and inflammation, which may participate in diabetic complications. We investigated the association of serum ADA levels with prolonged QTc interval in a large-scale sample of patients with T2D.
Methods
In this cross-sectional study, a total of 492 patients with T2D were recruited. Serum ADA levels were determined by venous blood during fasting. QTc interval was estimated from resting 12-lead ECGs, and prolonged QTc interval was defined as QTc > 440 ms.
Results
In this study, the prevalence of prolonged QTc interval was 22.8%. Serum ADA levels were positively associated with QTc interval (r = 0.324, P < 0.0001). The proportion of participants with prolonged QTc interval increased significantly from 9.2% in the first tertile (T1) to 24.7% in the second tertile (T2) and 39.0% in the third tertile (T3) of ADA (P for trend < 0.001). After adjusting for other possible risk factors by multiple linear regression analysis, serum ADA level was still significantly associated with QTc interval (β = 0.217, t = 3.400, P < 0.01). Multivariate logistic regression analysis showed that female (OR 5.084, CI 2.379–10.864, P < 0.001), insulin-sensitizers treatment (OR 4.229, CI 1.290–13.860, P = 0.017) and ADA (OR 1.212, CI 1.094–1.343, P < 0.001) were independent contributors to prolonged QTc interval.
Conclusions
Serum ADA levels were independently associated with prolonged QTc interval in patients with T2D.
Search for other papers by Estíbaliz Castillero in
Google Scholar
PubMed
Search for other papers by Ana Isabel Martín in
Google Scholar
PubMed
Search for other papers by Maria Paz Nieto-Bona in
Google Scholar
PubMed
Search for other papers by Carmen Fernández-Galaz in
Google Scholar
PubMed
Search for other papers by María López-Menduiña in
Google Scholar
PubMed
Search for other papers by María Ángeles Villanúa in
Google Scholar
PubMed
Search for other papers by Asunción López-Calderón in
Google Scholar
PubMed
Chronic inflammation induces skeletal muscle wasting and cachexia. In arthritic rats, fenofibrate, a peroxisome proliferator-activated receptor α (PPARα (PPARA)) agonist, reduces wasting of gastrocnemius, a predominantly glycolytic muscle, by decreasing atrogenes and myostatin. Considering that fenofibrate increases fatty acid oxidation, the aim of this study was to elucidate whether fenofibrate is able to prevent the effect of arthritis on serum adipokines and on soleus, a type I muscle in which oxidative metabolism is the dominant source of energy. Arthritis was induced by injection of Freund's adjuvant. Four days after the injection, control and arthritic rats were gavaged daily with fenofibrate (300 mg/kg bw) or vehicle over 12 days. Arthritis decreased serum leptin, adiponectin, and insulin (P<0.01) but not resistin levels. In arthritic rats, fenofibrate administration increased serum concentrations of leptin and adiponectin. Arthritis decreased soleus weight, cross-sectional area, fiber size, and its Ppar α mRNA expression. In arthritic rats, fenofibrate increased soleus weight, fiber size, and Ppar α expression and prevented the increase in Murf1 mRNA. Fenofibrate decreased myostatin, whereas it increased MyoD (Myod1) and myogenin expressions in the soleus of control and arthritic rats. These data suggest that in oxidative muscle, fenofibrate treatment is able to prevent arthritis-induced muscle wasting by decreasing Murf1 and myostatin expression and also by increasing the myogenic regulatory factors, MyoD and myogenin. Taking into account the beneficial action of adiponectin on muscle wasting and the correlation between adiponectin and soleus mass, part of the anticachectic action of fenofibrate may be mediated through stimulation of adiponectin secretion.
Search for other papers by Helle Keinicke in
Google Scholar
PubMed
Search for other papers by Gao Sun in
Google Scholar
PubMed
Search for other papers by Caroline M Junker Mentzel in
Google Scholar
PubMed
Search for other papers by Merete Fredholm in
Google Scholar
PubMed
Search for other papers by Linu Mary John in
Google Scholar
PubMed
Search for other papers by Birgitte Andersen in
Google Scholar
PubMed
Search for other papers by Kirsten Raun in
Google Scholar
PubMed
Search for other papers by Marina Kjaergaard in
Google Scholar
PubMed
The prevalence of non-alcoholic fatty liver disease (NAFLD) has increased dramatically worldwide and, subsequently, also the risk of developing non-alcoholic steatohepatitis (NASH), hepatic fibrosis, cirrhosis and cancer. Today, weight loss is the only available treatment, but administration of fibroblast growth factor 21 (FGF21) analogues have, in addition to weight loss, shown improvements on liver metabolic health but the mechanisms behind are not entirely clear. The aim of this study was to investigate the hepatic metabolic profile in response to FGF21 treatment. Diet-induced obese (DIO) mice were treated with s.c. administration of FGF21 or subjected to caloric restriction by switching from high fat diet (HFD) to chow to induce 20% weight loss and changes were compared to vehicle dosed DIO mice. Cumulative caloric intake was reduced by chow, while no differences were observed between FGF21 and vehicle dosed mice. The body weight loss in both treatment groups was associated with reduced body fat mass and hepatic triglycerides (TG), while hepatic cholesterol was slightly decreased by chow. Liver glycogen was decreased by FGF21 and increased by chow. The hepatic gene expression profiles suggest that FGF21 increased uptake of fatty acids and lipoproteins, channeled TGs toward the production of cholesterol and bile acid, reduced lipogenesis and increased hepatic glucose output. Furthermore, FGF21 appeared to reduce inflammation and regulate hepatic leptin receptor-a expression. In conclusion, FGF21 affected several metabolic pathways to reduce hepatic steatosis and improve hepatic health and markedly more genes than diet restriction (61 vs 16 out of 89 investigated genes).
Department of Rheumatology and Clinical Immunology, Charité-University Medicine, Berlin, Germany
Search for other papers by Janko Sattler in
Google Scholar
PubMed
Bone Research Program, ANZAC Research Institute, University of Sydney, Sydney, NSW, Australia
Concord Clinical School, The University of Sydney, Sydney, Australia
Search for other papers by Jinwen Tu in
Google Scholar
PubMed
Search for other papers by Shihani Stoner in
Google Scholar
PubMed
Key Laboratory for Space Bioscience and Biotechnology, Institute of Special Environmental Biophysics, School of Life Sciences, Northwestern Polytechnical University, Shaanxi, China
Search for other papers by Jingbao Li in
Google Scholar
PubMed
Search for other papers by Frank Buttgereit in
Google Scholar
PubMed
Concord Clinical School, The University of Sydney, Sydney, Australia
Department of Endocrinology & Metabolism, Concord Hospital, Sydney, Australia
Search for other papers by Markus J Seibel in
Google Scholar
PubMed
Concord Clinical School, The University of Sydney, Sydney, Australia
Search for other papers by Hong Zhou in
Google Scholar
PubMed
Concord Clinical School, The University of Sydney, Sydney, Australia
Department of Endocrinology & Metabolism, Concord Hospital, Sydney, Australia
Search for other papers by Mark S Cooper in
Google Scholar
PubMed
Patients with chronic immune-mediated arthritis exhibit abnormal hypothalamo-pituitary-adrenal (HPA) axis activity. The basis for this abnormality is not known. Immune-mediated arthritis is associated with increased extra-adrenal synthesis of active glucocorticoids by the 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) enzyme. 11β-HSD1 is expressed in the central nervous system, including regions involved in HPA axis regulation. We examined whether altered 11β-HSD1 expression within these regions contributes to HPA axis dysregulation during arthritis. The expression of 11β-HSD1, and other components of glucocorticoid signaling, were examined in various brain regions and the pituitary gland of mice with experimentally induced arthritis. Two arthritis protocols were employed: The K/BxN spontaneous arthritis model for chronic arthritis and the K/BxN serum transfer arthritis model for acute arthritis. 11β-HSD1 mRNA (Hsd11b1) was expressed in the hippocampus, hypothalamus, cortex, cerebellum and pituitary gland. Hypothalamic Hsd11b1 expression did not change in response to arthritis in either model. Pituitary Hsd11b1 expression was however significantly increased in both chronic and acute arthritis models. Hippocampal Hsd11b1 was decreased in acute but not chronic arthritis. Chronic, but not acute, arthritis was associated with a reduction in hypothalamic corticotropin-releasing hormone and arginine vasopressin expression. In both models, serum adrenocorticotropic hormone and corticosterone levels were no different from non-inflammatory controls. These findings demonstrate inflammation-dependent regulation of Hsd11b1 expression in the pituitary gland and hippocampus. The upregulation of 11β-HSD1 expression in the pituitary during both chronic and acute arthritis, and thus, an increase in glucocorticoid negative feedback, could contribute to the abnormalities in HPA axis activity seen in immune-mediated arthritis.
