RESUMEN
Vitamin D contributes to blood pressure (BP) regulation. We compared the association of BP in diabetic patients with either total vitamin D - the standard way of analyzing the vitamin D status - or free vitamin D, because only free vitamin D passes the cell membrane and interacts with the nuclear vitamin D receptor (VDR). An analytical cross-sectional study was conducted with 178 diabetic patients with impaired kidney function. Free and total vitamin D concentrations were measured in all patients. Multiple linear regression analysis considering patient age, sex, body mass index, height, smoking and drinking situation, the use of antihypertensive drugs, cholecalciferol treatment, C-reactive protein and estimated glomerular filtration rate as confounding factors were conducted to compare the association of free and total vitamin D with systolic and diastolic blood pressure (SBP and DBP). Multiple linear regression analysis revealed that neither SBP nor DBP was correlated with total vitamin D (SBP, 95% CI -0.405 ~ 0.159, p = 0.390; DBP, 95% CI -0.131 ~ 0.142, p = 0.933) (Table 2). However, the concentration of free vitamin D was independently associated with SBP (95% CI -2.691 ~ -0.210; p = 0.022) (Table 3), but not with DBP (95% CI -0.934 ~ 0.285; p = 0.293). In conclusion, free - but not total - vitamin D serum concentrations in patients with diabetes and impaired kidney function are inversely correlated with SBP. This study suggests that free vitamin D measurements might be more clinically relevant - as compared to measurements of total vitamin D - to adjust vitamin D therapy in diabetic patients with impaired kidney function.
Asunto(s)
Diabetes Mellitus , Hipertensión , Presión Sanguínea , Estudios Transversales , Humanos , Hipertensión/diagnóstico , Hipertensión/tratamiento farmacológico , Riñón , Vitamina DRESUMEN
BACKGROUND: Generalized anxiety disorder (GAD) is a common chronic mental disorder, and it also can cause depressive symptoms and cognitive impairment. The primary aim of this study was to determine whether inflow-frequency transcranial magnetic stimulation (ILF-TMS) improves anxiety symptoms in patients with GAD. METHODS: Sixty-two patients with GAD were randomly divided into 2 groups. Thirty-one patients in the active ILF-TMS group and 31 patients in the sham ILF-TMS group. All participants were assessed at baseline, week 2, week 4 and week 12. The intention-to-treat methodology was used for the analysis. RESULTS: The response rate was higher in the active group than in the sham group, with a significant difference at week 12 (response rate: 80.6% vs. 54.8%, respectively; Pâ¯=â¯0.03). Although the remission rate was higher in the active group at week 12, there was no statistically significant difference between the groups (remission rate: 71.0% vs. 48.4%; Pâ¯>â¯0.05). No statistically significant differences on the Hamilton Depression Rating Scale, Clinical Global Impression scale, and neurocognitive test between groups were observed (overall Pâ¯>â¯0.05). Adverse events that occurred in the active group were similar to those in the sham group, with no significant differences (Pâ¯>â¯0.05). CONCLUSION: The response rate was higher in the active group at the end of the trial, which indicated that ILF-TMS may be an effective and safe adjunctive tool to improve anxiety symptoms in patients with GAD.
RESUMEN
BACKGROUND: Host factors such as angiotensin-converting enzyme 2 (ACE2) and the transmembrane protease, serine-subtype-2 (TMPRSS2) are important factors for SARS-CoV-2 infection. Clinical and pre-clinical studies demonstrated that RAAS-blocking agents can be safely used during a SARS-CoV-2 infection but it is unknown if DPP-4 inhibitors or SGLT2-blockers may promote COVID-19 by increasing the host viral entry enzymes ACE2 and TMPRSS2. METHODS: We investigated telmisartan, linagliptin and empagliflozin induced effects on renal and cardiac expression of ACE2, TMPRSS2 and key enzymes involved in RAAS (REN, AGTR2, AGT) under high-salt conditions in a non-diabetic experimental 5/6 nephrectomy (5/6 Nx) model. In the present study, the gene expression of Ace2, Tmprss2, Ren, Agtr2 and Agt was assessed with qRT-PCR and the protein expression of ACE2 and TMPRSS2 with immunohistochemistry in the following experimental groups: Sham + normal diet (ND) + placebo (PBO); 5/6Nx + ND + PBO; 5/6Nx + high salt-diet (HSD) + PBO; 5/6Nx + HSD + telmisartan; 5/6Nx + HSD + linagliptin; 5/6Nx + HSD + empagliflozin. RESULTS: In the kidney, the expression of Ace2 was not altered on mRNA level under disease and treatment conditions. The renal TMPRSS2 levels (mRNA and protein) were not affected, whereas the cardiac level was significantly increased in 5/6Nx rats. Intriguingly, the elevated TMPRSS2 protein expression in the heart was significantly normalized after treatment with telmisartan, linagliptin and empagliflozin. CONCLUSIONS: Our study indicated that there is no upregulation regarding host factors potentially promoting SARS-CoV-2 virus entry into host cells when the SGLT2-blocker empagliflozin, telmisartan and the DPP4-inhibitor blocker linagliptin are used. The results obtained in a preclinical, experimental non-diabetic kidney failure model need confirmation in ongoing interventional clinical trials.
Asunto(s)
Tratamiento Farmacológico de COVID-19 , Inhibidores de la Dipeptidil-Peptidasa IV , Antagonistas de Receptores de Angiotensina , Inhibidores de la Enzima Convertidora de Angiotensina , Animales , Inhibidores de la Dipeptidil-Peptidasa IV/farmacología , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Humanos , Riñón/metabolismo , Nefrectomía , Ratas , SARS-CoV-2 , Transportador 2 de Sodio-Glucosa , Glicoproteína de la Espiga del Coronavirus/genética , Glicoproteína de la Espiga del Coronavirus/metabolismoRESUMEN
Fibroblast growth factor 23 (FGF23) and parathyroid hormone (PTH) are regulators of renal phosphate excretion and vitamin D metabolism. In chronic kidney disease (CKD), circulating FGF23 and PTH concentrations progressively increase as renal function declines. Oxidation of PTH at two methionine residues (positions 8 and 18) causes a loss of function. The impact of n-oxPTH and oxPTH on FGF23 synthesis, however, and how n-oxPTH and oxPTH concentrations are affected by CKD, is yet unknown. The effects of oxidized and non-oxidized PTH 1-34 on Fgf23 gene expression were analyzed in UMR106 osteoblast-like cells. Furthermore, we investigated the relationship between n-oxPTH and oxPTH, respectively, with FGF23 in two independent patients' cohorts (620 children with CKD and 600 kidney transplant recipients). While n-oxPTH stimulated Fgf23 mRNA synthesis in vitro, oxidation of PTH in particular at Met8 led to a markedly weaker stimulation of Fgf23. The effect was even stronger when both Met8 and Met18 were oxidized. In both clinical cohorts, n-oxPTH-but not oxPTH-was significantly associated with FGF23 concentrations, independent of known confounding factors. Moreover, with progressive deterioration of kidney function, intact PTH (iPTH) and oxPTH increased substantially, whereas n-oxPTH increased only moderately. In conclusion, n-oxPTH, but not oxPTH, stimulates Fgf23 gene expression. The increase in PTH with decreasing GFR is mainly due to an increase in oxPTH in more advanced stages of CKD.
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Factores de Crecimiento de Fibroblastos/metabolismo , Tasa de Filtración Glomerular , Osteoblastos/patología , Hormona Paratiroidea/química , Hormona Paratiroidea/metabolismo , Insuficiencia Renal Crónica/patología , Adolescente , Animales , Niño , Femenino , Factor-23 de Crecimiento de Fibroblastos , Factores de Crecimiento de Fibroblastos/genética , Humanos , Masculino , Osteoblastos/metabolismo , Oxidación-Reducción , Estudios Prospectivos , Ratas , Insuficiencia Renal Crónica/genética , Insuficiencia Renal Crónica/metabolismoRESUMEN
AIMS: Angiotensin-converting enzyme-2 (ACE2) is the receptor for SARS-CoV-2. Animal studies suggest that renin-angiotensin-aldosterone system (RAAS) blockers might increase the expression of ACE2 and potentially increase the risk of SARS-CoV-2 infection. METHODS AND RESULTS: The effect of ACE inhibitor (ACEI) treatment on the pneumonia incidence in non-COVID-19 patients (25 studies, 330 780 patients) was associated with a 26% reduction of pneumonia risk (odds ratio [OR]: 0.74, P < .001). Pneumonia-related death cases in ACEI-treated non-COVID-19 patients were reduced by 27% (OR: 0.73, P = .004). However, angiotensin II receptor blockers (ARB) treatment (10 studies, 275 621 non-COVID-19 patients) did not alter pneumonia risk in patients. Pneumonia-related death cases in ARB-treated non-COVID-19 patients was analysed only in 1 study and was significantly reduced (OR, 0.47; 95% confidence interval, 0.30 to 0.72). Results from 11 studies (8.4 million patients) showed that the risk of getting infected with the SARS-CoV-2 virus was reduced by 13% (OR: 0.87, P = .014) in patients treated with ACEI, whereas analysis from 10 studies (8.4 million patients) treated with ARBs showed no effect (OR, 0.92, P = .354). Results from 34 studies in 67 644 COVID-19 patients showed that RAAS blockade reduces all-cause mortality by 24% (OR = 0.76, P = .04). CONCLUSION: ACEIs reduce the risk of getting infected with the SARS-CoV-2 virus. Blocking the RAAS may decrease all-cause mortality in COVID-19 patients. ACEIs also reduce the risk of non-COVID pneumonia. All-cause mortality due to non-COVID pneumonia is reduced by ACEI and potentially by ARBs.
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Antagonistas de Receptores de Angiotensina/uso terapéutico , COVID-19/fisiopatología , Sistema Renina-Angiotensina/fisiología , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Animales , COVID-19/epidemiología , COVID-19/patología , Humanos , Hipertensión/complicaciones , Pulmón , SARS-CoV-2RESUMEN
BACKGROUND: Vascular calcification is common in chronic kidney disease and is associated with significant cardiovascular morbidity and mortality. One of the important factors regulating vascular calcification is osteoprotegerin (OPG). There are, however, limited data on the impact of OPG on all-cause mortality and graft loss in kidney transplant recipients so far. Given its impact on vascular calcification, the aim of our study is to analyze whether OPG was a risk factor of all-cause mortality and graft loss in 600 stable kidney transplant recipients. MATERIALS AND METHODS: 600 stable renal transplant recipients (367 women, 233 men) were followed for all-cause mortality and graft loss for 3 years. Blood and urine samples for analysis and clinical data were collected at study entry. We performed Kaplan-Meier survival analysis and Cox regression models considering confounding factors such as age, estimated glomerular filtration rate (eGFR), cold ischemia time, HbA1c, phosphorus, calcium, and albumin. RESULTS: 65 patients died, and 38 patients had graft loss during the observation period. The OPG baseline concentrations had no effect on graft loss, whereas Kaplan-Meier survival curve showed that baseline plasma OPG concentrations were associated with all-cause mortality in stable kidney transplant recipients (p < 0.0001, log-rank test). After multiple Cox regression analysis adjusting for age, eGFR, cold ischemia time, HbA1c, phosphorus, calcium, and albumin, plasma levels of OPG remained an independent predictor of all-cause mortality (HR, 1.181; 95%CI 1.035 - 1.347; p = 0.014). CONCLUSION: Baseline plasma OPG is an independent risk factor for all-cause mortality but not graft loss in patients after kidney transplantation.
Asunto(s)
Trasplante de Riñón , Osteoprotegerina , Biomarcadores , Femenino , Humanos , Trasplante de Riñón/efectos adversos , Masculino , Factores de Riesgo , Receptores de TrasplantesRESUMEN
BACKGROUND: Increased fibroblast growth factor 23 (FGF23) is a risk factor for mortality, cardiovascular disease, and progression of chronic kidney disease. Limited data exist comparing the association of either c-terminal FGF23 (cFGF23) or intact FGF23 (iFGF23) in kidney transplant recipients (KTRs) with overall (all-cause) graft loss. METHODS: We conducted a prospective observational cohort study in 562 stable kidney transplant recipients. Patients were followed for graft loss and all-cause mortality for a median follow-up of 48 months. RESULTS: During a median follow-up of 48 months, 94 patients had overall graft loss (primary graft loss or death with functioning graft). Both cFGF23 and iFGF23 concentrations were significantly higher in patients with overall graft loss than those without (24.59 [11.43-87.82] versus 10.67 [5.99-22.73] pg/ml; p < 0.0001 and 45.24 [18.63-159.00] versus 29.04 [15.23-60.65] pg/ml; p = 0.002 for cFGF23 and iFGF23, respectively). Time-dependent ROC analysis showed that cFGF23 concentrations had a better discriminatory ability than iFGF23 concentrations in predicting overall (all-cause) graft loss. Cox regression analyses adjusted for risk factors showed that cFGF23 (HR for one unit increase of log transformed cFGF23: 1.35; 95% CI, 1.01-1.79; p = 0.043) but not iFGF23 (HR for one unit increase of log transformed iFGF23: 0.97; 95% CI, 0.75-1.25; p = 0.794) was associated with the overall graft loss. CONCLUSION: Elevated cFGF23 concentrations at baseline are independently associated with an increased risk of overall graft loss. iFGF23 measurements were not independently associated with overall graft loss. The cFGF23 ELISA might detect bioactive FGF23 fragments that are not detected by the iFGF23 ELISA.
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Factor-23 de Crecimiento de Fibroblastos/sangre , Supervivencia de Injerto/fisiología , Trasplante de Riñón , Receptores de Trasplantes , Adulto , Anciano , Biomarcadores/sangre , Causas de Muerte , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Enfermedades Renales/cirugía , Trasplante de Riñón/mortalidad , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Curva ROC , Factores de RiesgoRESUMEN
Fibroblast growth factor 23 (FGF23) is produced by bone cells and regulates renal phosphate and vitamin D metabolism, as well as causing left ventricular hypertrophy. FGF23 deficiency results in rapid aging, whereas high plasma FGF23 levels are found in several disorders, including kidney or cardiovascular diseases. Regulators of FGF23 production include parathyroid hormone (PTH), calcitriol, dietary phosphate, and inflammation. We report that insulin and insulin-like growth factor 1 (IGF1) are negative regulators of FGF23 production. In UMR106 osteoblast-like cells, insulin and IGF1 down-regulated FGF23 production by inhibiting the transcription factor forkhead box protein O1 (FOXO1) through phosphoinositide 3-kinase (PI3K)/protein kinase B (PKB)/Akt signaling. Insulin deficiency caused a surge in the serum FGF23 concentration in mice, which was reversed by administration of insulin. In women, a highly significant negative correlation between FGF23 plasma concentration and increase in plasma insulin level following an oral glucose load was found. Our results provide strong evidence that insulin/IGF1-dependent PI3K/PKB/Akt/FOXO1 signaling is a powerful suppressor of FGF23 production in vitro as well as in mice and in humans.
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Factores de Crecimiento de Fibroblastos/metabolismo , Regulación de la Expresión Génica/fisiología , Insulina/fisiología , Animales , Línea Celular Tumoral , Diabetes Mellitus Experimental/metabolismo , Femenino , Factor-23 de Crecimiento de Fibroblastos , Factores de Crecimiento de Fibroblastos/sangre , Glucosa/administración & dosificación , Glucosa/metabolismo , Glucuronidasa/metabolismo , Humanos , Insulina/sangre , Insulina/metabolismo , Proteínas Klotho , Masculino , Ratones , Fosfatidilinositol 3-Quinasas/metabolismo , Embarazo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas , Transducción de Señal/fisiologíaRESUMEN
BACKGROUND: Endostatin is a 20-kDa C-terminal fragment of collagen XVIII, known for its ability to inhibit the proliferation of capillary endothelial cells. Previous studies suggested that circulating endostatin independently predicts incident chronic kidney disease. However, the impact of endostatin on graft loss level in kidney transplant recipients (KTRs) remains unknown. METHODS: We conducted a prospective observational cohort study in 574 maintenance KTRs. Patients were followed for kidney graft loss and all-cause mortality during a median follow-up of 48 months. Serum-, and urine-samples and clinical data were collected at baseline. Serum Endostatin concentration was analyzed by an ELISA. RESULTS: Among 574 patients, 37 patients had graft loss and 62 patients died. For graft loss, the optimal cut-off value based on receiver operating characteristics analysis (area under the curve 0.79, 95% CI 0.71-0.86, p < 0.001) of endostatin was 147.3 pmol/L. Kaplan-Meier curves revealed that higher serum endostatin concentrations positively correlated with graft loss (p < 0.001). Multivariable Cox regression analyses showed that baseline endostatin concentrations were significantly associated with graft loss after adjusting for graft loss risk factors (adjusted hazard ratio [HR] 8.34; 95% CI 2.19-31.72; p = 0.002). The adjusted HRs for classical graft loss risk factors such as baseline estimated glomerular filtration rate and urinary protein excretion were lower (1.91 and 5.44, respectively). In contrast to graft loss, baseline endostatin concentrations were not associated with all-cause mortality. CONCLUSION: Increased serum endostatin at baseline is independently associated with the risk of graft loss in KTRs.
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Endostatinas/sangre , Rechazo de Injerto/epidemiología , Fallo Renal Crónico/cirugía , Trasplante de Riñón/efectos adversos , Adulto , Anciano , Biomarcadores/sangre , Estudios Transversales , Femenino , Estudios de Seguimiento , Tasa de Filtración Glomerular , Rechazo de Injerto/etiología , Humanos , Estimación de Kaplan-Meier , Fallo Renal Crónico/mortalidad , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Valores de Referencia , Medición de Riesgo/métodos , Factores de RiesgoRESUMEN
BACKGROUND: Sclerostin is a hormone contributing to the bone-vascular wall cross talk and has been implicated in cardiovascular events and mortality in patients with chronic kidney disease (CKD). We analyzed the relationship between sclerostin and mortality in renal transplant recipients. METHODS: 600 stable renal transplant recipients (367men, 233 women) were followed for all-cause mortality for 3 years. Blood and urine samples for analysis and clinical data were collected at study entry. We performed Kaplan-Meier survival analysis and Cox regression models considering confounding factors such as age, eGFR, cold ischemia time, HbA1c, phosphate, calcium, and albumin. Optimal cut-off values for the Cox regression model were calculated based on ROC analysis. RESULTS: Sixty-five patients died during the observation period. Nonsurvivors (n = 65; sclerostin 57.31 ± 30.28 pmol/L) had higher plasma sclerostin levels than survivors (n = 535; sclerostin 47.52 ± 24.87 pmol/L) (p = 0.0036). Kaplan-Meier curve showed that baseline plasma sclerostin concentrations were associated with all-cause mortality in stable kidney transplant recipients (p = 0.0085, log-rank test). After multiple Cox regression analysis, plasma levels of sclerostin remained an independent predictor of all-cause mortality (hazard ratio, 1.011; 95% CI 1.002-1.020; p = 0.0137). CONCLUSIONS: Baseline plasma sclerostin is an independent risk factor for all-cause mortality in patients after kidney transplantation.
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Proteínas Adaptadoras Transductoras de Señales/sangre , Trasplante de Riñón/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Femenino , Humanos , Trasplante de Riñón/efectos adversos , Masculino , Persona de Mediana Edad , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Regulación hacia Arriba , Adulto JovenRESUMEN
Dipeptidyl peptidase type 4 (DPP-4) inhibitors were reported to have beneficial effects in experimental models of chronic kidney disease. The underlying mechanisms are not completely understood. However, these effects could be mediated via the glucagon-like peptide-1 (GLP-1)/GLP-1 receptor (GLP1R) pathway. Here we investigated the renal effects of the DPP-4 inhibitor linagliptin in Glp1r-/- knock out and wild-type mice with 5/6 nephrectomy (5/6Nx). Mice were allocated to groups: sham+wild type+placebo; 5/6Nx+ wild type+placebo; 5/6Nx+wild type+linagliptin; sham+knock out+placebo; 5/6Nx+knock out+ placebo; 5/6Nx+knock out+linagliptin. 5/6Nx caused the development of renal interstitial fibrosis, significantly increased plasma cystatin C and creatinine levels and suppressed renal gelatinase/collagenase, matrix metalloproteinase-1 and -13 activities; effects counteracted by linagliptin treatment in wildtype and Glp1r-/- mice. Two hundred ninety-eight proteomics signals were differentially regulated in kidneys among the groups, with 150 signals specific to linagliptin treatment as shown by mass spectrometry. Treatment significantly upregulated three peptides derived from collagen alpha-1(I), thymosin ß4 and heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1) and significantly downregulated one peptide derived from Y box binding protein-1 (YB-1). The proteomics results were further confirmed using western blot and immunofluorescence microscopy. Also, 5/6Nx led to significant up-regulation of renal transforming growth factor-ß1 and pSMAD3 expression in wild type mice and linagliptin significantly counteracted this up-regulation in wild type and Glp1r-/- mice. Thus, the renoprotective effects of linagliptin cannot solely be attributed to the GLP-1/GLP1R pathway, highlighting the importance of other signaling pathways (collagen I homeostasis, HNRNPA1, YB-1, thymosin ß4 and TGF-ß1) influenced by DPP-4 inhibition.
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Inhibidores de la Dipeptidil-Peptidasa IV/farmacología , Riñón/efectos de los fármacos , Linagliptina/farmacología , Insuficiencia Renal Crónica/tratamiento farmacológico , Transducción de Señal/efectos de los fármacos , Animales , Colágeno Tipo I/metabolismo , Cadena alfa 1 del Colágeno Tipo I , Dipeptidil Peptidasa 4/metabolismo , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Modelos Animales de Enfermedad , Regulación hacia Abajo/efectos de los fármacos , Receptor del Péptido 1 Similar al Glucagón/genética , Ribonucleoproteína Nuclear Heterogénea A1/metabolismo , Humanos , Riñón/patología , Riñón/cirugía , Linagliptina/uso terapéutico , Masculino , Ratones , Ratones Noqueados , Nefrectomía/efectos adversos , RNA-Seq , Insuficiencia Renal Crónica/etiología , Insuficiencia Renal Crónica/patología , Timosina/metabolismo , Factores de Transcripción/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo , Regulación hacia Arriba/efectos de los fármacosRESUMEN
BACKGROUND/AIMS: Impaired birth outcomes, like low birth weight, have consistently been associated with increased disease susceptibility to hypertension in later life. Alterations in the maternal or fetal metabolism might impact on fetal growth and influence birth outcomes. Discerning associations between the maternal and fetal metabolome and surrogate parameters of fetal growth could give new insight into the complex relationship between intrauterine conditions, birth outcomes, and later life disease susceptibility. METHODS: Using flow injection tandem mass spectrometry, targeted metabolomics was performed in serum samples obtained from 226 mother/child pairs at delivery. Associations between neonatal birth weight and concentrations of 163 maternal and fetal metabolites were analyzed. RESULTS: After FDR adjustment using the Benjamini-Hochberg procedure lysophosphatidylcholines (LPC) 14: 0, 16: 1, and 18: 1 were strongly positively correlated with birth weight. In a stepwise linear regression model corrected for established confounding factors of birth weight, LPC 16: 1 showed the strongest independent association with birth weight (CI: 93.63 - 168.94; P = 6.94×10-11 ). The association with birth weight was stronger than classical confounding factors such as offspring sex (CI: -258.81- -61.32; P = 0.002) and maternal smoking during pregnancy (CI: -298.74 - -29.51; P = 0.017). CONCLUSIONS: After correction for multiple testing and adjustment for potential confounders, LPC 16: 1 showed a very strong and independent association with birth weight. The underlying molecular mechanisms linking fetal LPCs with birth weight need to be addressed in future studies.
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Peso al Nacer , Sangre Fetal/metabolismo , Lisofosfatidilcolinas/análisis , Adulto , Femenino , Humanos , Recién Nacido , Modelos Lineales , Lisofosfatidilcolinas/química , Masculino , Metabolómica , Embarazo , Factores Sexuales , Fumar , Espectrometría de Masas en TándemRESUMEN
BACKGROUND/AIMS: Angiogenesis is a key feature during embryo development but is also part of the pathogenesis of cancer in adult life. Angiogenesis might be modulated by inflammation. METHODS: We established an angiogenesis model in chick chorioallantoic membrane (CAM) induced by the exposure of lipopolysaccharide (LPS), and analyzed the effects of the antioxidant N-acetylcysteine (NAC) on angiogenesis in this model as well as on the expression of key genes known to involved in the regulation of angiogenesis. RESULTS: Treatment with NAC was able to normalize LPS induced angiogenesis and restore the LPS-induced damage of vascular epithelium in chick CAM. Using quantitative PCR, we showed that NAC administration normalized the LPS induced expression of Keap1-Nrf2 signaling and oxidative stress key enzyme gene expressions (SOD, GPx and YAP1). CONCLUSION: We established a LPS-induced angiogenesis model in chick CAM. NAC administration could effectively inhibit LPS-induced angiogenesis and restore the integrity of endothelium on chick CAM. LPS exposure caused an increased expression of genes involved in oxidative stress in chick CAM. NAC administration could abolish this effect.
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Acetilcisteína/farmacología , Antioxidantes/farmacología , Lipopolisacáridos/farmacología , Neovascularización Fisiológica/efectos de los fármacos , Angiotensinas/genética , Angiotensinas/metabolismo , Animales , Aorta Torácica/efectos de los fármacos , Aorta Torácica/fisiología , Embrión de Pollo , Pollos , Membrana Corioalantoides/efectos de los fármacos , Membrana Corioalantoides/metabolismo , Claudinas/genética , Claudinas/metabolismo , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , Estrés Oxidativo/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Superóxido Dismutasa/genética , Superóxido Dismutasa/metabolismoRESUMEN
BACKGROUND/AIMS: Angiogenesis plays a key role during embryonic development. The vascular endothelin (ET) system is involved in the regulation of angiogenesis. Lipopolysaccharides (LPS) could induce angiogenesis. The effects of ET blockers on baseline and LPS-stimulated angiogenesis during embryonic development remain unknown so far. METHODS: The blood vessel density (BVD) of chorioallantoic membranes (CAMs), which were treated with saline (control), LPS, and/or BQ123 and the ETB blocker BQ788, were quantified and analyzed using an IPP 6.0 image analysis program. Moreover, the expressions of ET-1, ET-2, ET3, ET receptor A (ETRA), ET receptor B (ETRB) and VEGFR2 mRNA during embryogenesis were analyzed by semi-quantitative RT-PCR. RESULTS: All components of the ET system are detectable during chicken embryogenesis. LPS increased angiogenesis substantially. This process was completely blocked by the treatment of a combination of the ETA receptor blockers-BQ123 and the ETB receptor blocker BQ788. This effect was accompanied by a decrease in ETRA, ETRB, and VEGFR2 gene expression. However, the baseline angiogenesis was not affected by combined ETA/ETB receptor blockade. CONCLUSION: During chicken embryogenesis, the LPS-stimulated angiogenesis, but not baseline angiogenesis, is sensitive to combined ETA/ETB receptor blockade.
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Antagonistas de los Receptores de la Endotelina B/farmacología , Lipopolisacáridos/farmacología , Neovascularización Fisiológica/efectos de los fármacos , Receptor de Endotelina A/metabolismo , Receptor de Endotelina B/metabolismo , Animales , Pollos , Membrana Corioalantoides/efectos de los fármacos , Membrana Corioalantoides/metabolismo , Desarrollo Embrionario/efectos de los fármacos , Endotelina-1/genética , Endotelina-1/metabolismo , Oligopéptidos/farmacología , Péptidos Cíclicos/farmacología , Piperidinas/farmacología , Receptor de Endotelina A/química , Receptor de Endotelina A/genética , Receptor de Endotelina B/química , Receptor de Endotelina B/genética , Transducción de Señal/efectos de los fármacos , Receptor 2 de Factores de Crecimiento Endotelial Vascular/genética , Receptor 2 de Factores de Crecimiento Endotelial Vascular/metabolismoRESUMEN
BACKGROUND/AIMS: The ET system might be involved in the pathogenesis of hypertensive disorders during pregnancy. The objective is to analyse the impact of ET-1 in hypertensive pregnant women by a strict meta-analysis of published human clinical studies. METHODS: Based on the principle of Cochrane systematic reviews, Cohort studies in PubMed (Medline), Google Scholar and China Biological Medicine Database (CBM-disc) designed to identify the role of endothelin-1 (ET-1) in the pathophysiology of gestational hypertension and preeclampsia were screened. Review Manager Version 5.0 (Rev-Man 5.0) was applied for statistical analysis. Mean difference and 95% confidence interval (CI) were shown in inverse variance (IV) fixed-effects model or IV random-effects model. RESULTS: Sixteen published cohort studies including 1739 hypertensive cases and 409 controls were used in the meta-analysis. ET-1 plasma concentrations were higher in hypertensive pregnant women as compared to the controls (mean difference between groups: 19.02 [15.60ï½22.44], P < 0.00001,). These finding were driven by severity of hypertension and/or degree of proteinuria. CONCLUSION: Plasma ET-1 concentrations are elevated in hypertensive disorders during human pregnancy. In particular women with preeclampsia (hypertensive pregnant women with proteinuria) have substantially elevated plasma ET-1 concentration as compared to pregnant women with normal blood pressure.
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Endotelina-1/sangre , Hipertensión/fisiopatología , Complicaciones del Embarazo/fisiopatología , Femenino , Humanos , Hipertensión Inducida en el Embarazo/fisiopatología , Preeclampsia/fisiopatología , Embarazo , ProteinuriaRESUMEN
BACKGROUND: This study examines the relationship between eicosapentaenoic acid (EPA) intake from food and depression. EPA, an Omega-3 fatty acid commonly found in fish and seafood, has garnered attention for its potential role in depression prevention and treatment. METHODS: We selected 30,976 participants from the National Health and Nutrition Examination Survey (NHANES) conducted between 2005 and 2018. Depressive symptoms were diagnosed using the Patient Health Questionnaire (PHQ-9). EPA intake was assessed through dietary evaluation. Logistic regression and restricted cubic spline regression (RCS) were employed to assess the correlation between EPA and depressive symptom. RESULTS: The prevalence of depressive symptoms was 7.3 %. Participants with depressive symptoms exhibited lower EPA intake from food compared to non-depressed individuals. This negative association with depressive symptoms persisted even after accounting for various potential influencing factors (e.g., age, gender, body mass index, total energy intake, comorbidities). Notably, EPA demonstrated a nonlinear association with depressive symptoms, particularly in females. CONCLUSIONS: This study emphasizes a significant negative correlation between EPA consumption and depressive symptoms, particularly in females. This suggests that maintaining a rich EPA diet may play a role in depression prevention and treatment.
Asunto(s)
Ácido Eicosapentaenoico , Ácidos Grasos Omega-3 , Adulto , Femenino , Animales , Humanos , Depresión/epidemiología , Depresión/prevención & control , Encuestas Nutricionales , DietaRESUMEN
STUDY OBJECTIVES: This study aimed to investigate the unique characteristics and clinical significance of the nocturnal sleep onset rapid eye movement period (nSOREMP) in the Chinese population with narcolepsy, enhancing our understanding and management of the disorder globally. METHODS: This retrospective analysis investigated narcolepsy in Chinese patients from six hospitals, using the International Classification of Sleep Disorders. A parallel retrospective analysis of the Chinese Clinical Sleep Database focused on polysomnography records was conducted to evaluate nSOREMP prevalence in other sleep disorders. RESULTS: The study found a 2.51% nSOREMP prevalence in other sleep disorders in the Chinese Clinical Sleep Database. Significant differences in age, N2 and rapid eye movement percentages, rapid eye movement latency, and various indexes were noted among patients with narcolepsy with or without nSOREMP and other sleep disorders with nSOREMP in the Chinese Clinical Sleep Database. nSOREMP prevalence in narcolepsy type 1 was 33.33% and in narcolepsy type 2 was 28.30%. Noteworthy disparities in narcolepsy type 1 included N2 percentages, rapid eye movement latency, and SOREMPs on Multiple Sleep Latency Test. In narcolepsy type 2, differences were significant for age, sleep latency, N2 and rapid eye movement latencies, arousal index, mean sleep latency on the Multiple Sleep Latency Test, and Multiple Sleep Latency Test SOREMPs. CONCLUSIONS: This study highlights the distinct characteristics of nSOREMP in the Chinese population. Patients exhibiting symptoms suggestive of the onset of narcolepsy are advised to undergo a Multiple Sleep Latency Test, irrespective of the occurrence of SOREMP during nocturnal polysomnography. CITATION: Zeng S, Feng F, Li W, et al. Exploring sleep characteristics in Chinese patients with narcolepsy: insights from the nocturnal sleep onset rapid eye movement period (nSOREMP). J Clin Sleep Med. 2024;20(8):1349-1355.
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Narcolepsia , Polisomnografía , Sueño REM , Humanos , Narcolepsia/fisiopatología , Masculino , Femenino , Estudios Retrospectivos , Adulto , China/epidemiología , Sueño REM/fisiología , Persona de Mediana Edad , Prevalencia , Adolescente , Adulto Joven , Pueblos del Este de AsiaRESUMEN
STUDY OBJECTIVES: To investigate the cost-effectiveness of cognitive behavioral therapy for insomnia (CBTI), with an additional focus on digital CBTI (dCBTI) in adults with insomnia. METHODS: We searched eight electronic databases for economic evaluations of CBTI: PubMed, Scopus, Web of Science, psycINFO, Cochrane, Library, CINAHL, ProQuest, and National Health Service Economic Evaluation Database. Meta-analyses were performed to investigate the effects and costs between CBTI and control groups (no treatment, other treatments included hygiene education and treatment as usual). Subgroup analyses for dCBTI were conducted. RESULTS: Twelve randomized controlled trial studies between 2004 and 2023 were included in our systematic review and meta-analyses. The incremental cost-utility ratios and incremental cost-effectiveness ratios showed that the CBTI and dCBTI groups were more cost-effective than controls, from healthcare perspective and societal perspective, respectively. Compared to controls, CBTI demonstrated significantly better efficacy within 12 months. Healthcare costs were significantly higher in the CBTI groups compared to the controls within 6 months but there was no difference at 12 months. Additionally, dCBTI was associated with significantly lower presenteeism costs compared to controls at 6 months. CONCLUSIONS: Our findings suggest that CBTI is more cost-effective than other treatments or no treatment for adults with insomnia. It may bring more economic benefits in the long term, especially in long-lasting efficacy and cost reduction. In addition, dCBTI is one of the cost-effective options for insomnia. PROSPERO REGISTRATION NUMBER: CRD42â 022â 383â 440. URL: www.crd.york.ac.uk/PROSPERO. NAME FOR PROSPERO REGISTRATION: Cost-effectiveness of cognitive behavioral therapy for insomnia (CBTI): a systematic review with meta-analysis.
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Terapia Cognitivo-Conductual , Análisis Costo-Beneficio , Trastornos del Inicio y del Mantenimiento del Sueño , Humanos , Trastornos del Inicio y del Mantenimiento del Sueño/terapia , Trastornos del Inicio y del Mantenimiento del Sueño/economía , Terapia Cognitivo-Conductual/economía , Terapia Cognitivo-Conductual/métodos , Costos de la Atención en Salud/estadística & datos numéricosRESUMEN
Background: Vitamin D deficiency (VDD) or vitamin D insufficiency is common in kidney transplant recipients (KTRs). The impact of VDD on clinical outcomes in KTRs remain poorly defined and the most suitable marker for assessing vitamin D nutritional status in KTRs is unknown so far. Methods: We conducted a prospective study including 600 stable KTRs (367 men, 233 women) and a meta-analysis to pool existing evidence to determine whether 25(OH)D or 1,25(OH)2D predicted graft failure and all-cause mortality in stable KTRs. Results: Compared with a higher 25(OH)D concentration, a low concentration of 25(OH)D was a risk factor for graft failure (HR 0.946, 95% CI 0.912-0.981, p = 0.003), whereas 1,25 (OH)2D was not associated with the study end-point graft loss (HR 0.993, 95% CI 0.977-1.009, p = 0.402). No association was found between either 25(OH)D or 1,25 (OH)2D and all-cause mortality. We furthermore conducted a meta-analysis including 8 studies regarding the association between 25(OH)D or 1,25(OH)2D and graft failure or mortality, including our study. The meta-analysis results were consistent with our study in finding that lower 25(OH)D levels were significantly associated with the risk of graft failure (OR = 1.04, 95% CI: 1.01-1.07), but not associated with mortality (OR = 1.00, 95% CI: 0.98-1.03). Lower 1,25(OH)2D levels were not associated with the risk of graft failure (OR = 1.01, 95% CI: 0.99-1.02) and mortality (OR = 1.01, 95% CI: 0.99-1.02). Conclusion: Baseline 25(OH)D concentrations but not 1,25(OH)2D concentrations were independently and inversely associated with graft loss in adult KTRs.