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Vitamin D is a critical fat-soluble vitamin for the nervous system. Research suggests a potential link between vitamin D deficiency and attention-deficit hyperactivity disorder (ADHD), particularly in children and adolescents. The core symptoms of ADHD are associated with deficits in striatal functions, and maintaining sufficient levels of vitamin D may help prevent or alleviate ADHD symptoms. However, the molecular changes in the striatum caused by vitamin D supplementation that may contribute to the brain processes linked to ADHD symptoms remain unclear. In this study, we established a mouse model fed diets with three different dose gradients of vitamin D3 (0, 500, and 2000 IU/kg·day) from postnatal day 21 (P21) to 14 weeks of age. Striatal tissues from mice with gradient vitamin D3 intake were subjected to reduced representation bisulfite sequencing (RRBS), RNA-sequencing, and neurotransmitter profiling by liquid chromatography-mass spectrometry (LC-MS). Our findings indicate that vitamin D supplementation since childhood influenced the overall landscape of DNA methylations and the expression of many genes involved in critical neurological functions in a dose-dependent manner. Additionally, our data demonstrate how vitamin D modulated neuropeptide signaling pathways, as well as cholinergic and dopaminergic synapses in the striatum, through an orchestrated mechanism involving epigenetic and transcriptional regulations. Furthermore, we observed a synergistic effect of vitamin D on dopamine release following acute methylphenidate injection into our mouse model. In summary, this study provides mechanistic insights into how dietary vitamin D supplementation since childhood can modulate specific signal transductions among striatal cells, underscoring the importance of vitamin D supplementation for ADHD management.
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Objective: To observe the effect of lipid regulating therapy on carotid atherosclerotic plaque in diabetic patients. Methods: The REACH study, conducted between March 2009 and February 2012, enrolled asymptomatic patients with magnetic resonance imaging (MRI) confirmed carotid atherosclerotic plaque, who had never taken lipid-lowering drugs. Patients were treated with a moderate dose of rosuvastatin for 24 months. Blood lipid levels were measured and carotid MRI was performed at baseline, 3 and 24 months after treatment. The volume of carotid wall and lipid-rich necrotic core (LRNC) were measured by image analysis software. This study retrospectively analyzed patients in the REACH study. Patients were divided into diabetes group and non-diabetic group. The changes of blood lipid level and MRI parameters of carotid atherosclerotic plaque were compared between the two groups and their correlation was analyzed. Results: A total of 38 patients with carotid atherosclerotic plaque were included in this study, including 13 patients (34.2%) in the diabetic group and 25 patients (65.8%) in the non-diabetic group. Baseline parameters were comparable between the two groups, except higher HbA1c level in diabetes group (P<0.05). Compared with baseline, the total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) and triglyceride (TG) levels were significantly decreased at 3 and 24 months in both two groups (P<0.05). The change of high-density lipoprotein cholesterol (HDL-C) in diabetes group was not obvious, while it was significantly increased in non-diabetic group at 24 months ((1.38±0.33) mmol/l vs. (1.26±0.26) mmol/l, P<0.05). MRI results showed that the volume and percentage of LRNC remained unchanged at 3 months, slightly decreased at 24 months (64.86 (45.37, 134.56) mm3 vs. 75.76 (48.20, 115.64) mm3, P>0.05) and (15.84% (11.47%, 24.85%) vs. 16.95% (11.64%, 22.91%), P>0.05) in diabetic group. In non-diabetic group, the volume and percentage of LRNC were significantly decreased at 3 months (63.01 (44.25, 188.64) mm3 vs. 72.49 (51.91, 199.59) mm3, P<0.05) and (13.76% (8.81%, 27.64%) vs. 16.04% (11.18%, 27.05%), P<0.05) respectively. Both parameters further decreased to (55.63 (27.18, 179.40) mm3) and (12.71% (8.39%, 24.41%)) at 24 months (both P<0.05). Wall volume, lumen volume and percent wall volume (PWV) were not affected post therapy in both two groups(P>0.05). There were no correlations between the changes of plaque parameters including volume and percentage of LRNC, wall volume, lumen volume, PWV and the changes of blood lipid parameters (TC, LDL-C, HDL-C and TG) in 3 and 24 months (P>0.05). Conclusion: Lipid-lowering therapy possesses different effects on carotid atherosclerotic plaque in diabetic and non-diabetic patients, and the LRNC improvement is more significant in non-diabetic patients as compared to diabetic patients.
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Enfermedades de las Arterias Carótidas , Placa Aterosclerótica , Rosuvastatina Cálcica , Arterias Carótidas/diagnóstico por imagen , Arterias Carótidas/patología , Enfermedades de las Arterias Carótidas/diagnóstico por imagen , Enfermedades de las Arterias Carótidas/tratamiento farmacológico , HDL-Colesterol/uso terapéutico , LDL-Colesterol , Diabetes Mellitus , Humanos , Imagen por Resonancia Magnética/métodos , Necrosis/patología , Placa Aterosclerótica/diagnóstico por imagen , Placa Aterosclerótica/tratamiento farmacológico , Estudios Retrospectivos , Rosuvastatina Cálcica/uso terapéuticoRESUMEN
Objective: To explore the effect of remote "Internet+" interactive management strategy on blood pressure control in patients with hypertension during normalized epidemic prevention and control of COVID-19. Methods: This is a randomized controlled study. A total of 394 patients with hypertension who were treated in Chinese People's Liberation Army General Hospital from October 2019 to December 2020 were randomly divided into experimental group (197 cases) and control group (197 cases). The experimental group adopted remote "Internet+" interaction mode to carry out remote blood pressure intervention, and the control group received traditional blood pressure control mode, and the intervention time was 6 months. Evaluation indicators included blood pressure level, blood pressure lowering speed, time to target blood pressure, blood pressure measurement times, communication times with doctors, medication compliance, blood pressure measurement compliance and disease awareness after 6 months of intervention. The evaluation indexes of the two groups were compared, and the bivariate Pearson correlation analysis was used to explore the relationship between the speed of blood pressure reduction and the times of blood pressure measurement and doctor communication in all patients. Results: A total of 394 patients with hypertension were included in this study, including 209 males, aged (67.6±2.8) years old. After 6 months of intervention, the systolic and diastolic blood pressure of the two groups were both lower than the baseline blood pressure before intervention (both P<0.05), the systolic blood pressure ((125.7±11.7) mmHg (1 mmHg=0.133 kPa) vs. (132.6±12.9) mmHg, P<0.001) and diastolic blood pressure ((72.4±10.7) mmHg vs. (79.8±11.6) mmHg, P<0.001) in the experimental group were lower than those in the control group. The blood pressure reduction speed of the experimental group was faster than that of the control group ((18.63±1.59) mmHg/d vs. (13.26±2.85) mmHg/d, P<0.001), and the time to reach the target blood pressure in the experimental group was shorter than that in the control group ((23.69±2.93) d vs. (47.12±5.81) d, P<0.001). Compared with the control group, the blood pressure measurement times ((0.98±0.13) times/d vs. (0.20±0.40) times/d, P<0.05) and the number of communications with doctors ((0.97±0.16) times/week vs. (0.12±0.32) times/week, P<0.05) were significantly higher in the experimental group. Correlation analysis showed that the speed of blood pressure reduction was positively correlated with the number of blood pressure measurements (r=0.419, P<0.01) and the number of communications with doctors (r=0.857, P<0.01). The proportion of standardized medication (93.91% (185/197) vs. 51.78% (102/197), P<0.001), timely measurement (97.46% (192/197) vs. 47.21% (93/197), P<0.001) and high-degree disease awareness (94.42% (186/197) vs. 49.24% (97/197), P<0.001) were significantly higher in the experimental group than those in the control group. Conclusions: The remote "Internet+" interactive management strategy can effectively improve patients' blood pressure control. The doctor-patient interaction can improve medication compliance and measurement compliance of patients, and help shorten the time to reach the target blood pressure.
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COVID-19 , Epidemias , Hipertensión , Anciano , Presión Sanguínea , Humanos , Hipertensión/prevención & control , Internet , Masculino , Persona de Mediana Edad , SARS-CoV-2RESUMEN
Objective: To observe the biocompatibility of porcine omental derived extracellular matrix (ECM) hydrogel with human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and the feasibility of ECM hydrogel as a delivery vector of cell transplantation. Methods: A series of chemical, physical and enzymatic methods were applied to acellularize the porcine omentum. Subsequently, the extracted ECM was prepared into thermosensitive hydrogel. The biochemical composition of the hydrogel was identified by histological staining. The microstructure was observed by scanning electron microscopy. The hydrogel was then injected into the myocardium of mice to observe its in situ gelation ability. Differentiation of human induced pluripotent stem cells into cardiomyocytes was achieved by small molecule induction, and then the obtained hiPSC-CMs were cultured. hiPSC-CMs cultured onto the prepared hydrogel were defined as the hydrogel group, while conventionally cultured hiPSC-CMs were defined as the control group. Cardiomyocyte viability and growth patterns were detected using live/dead staining, CCK-8 and phalloidin staining. Immunofluorescence staining and Western blot of cardiomyocytes were used to determine the survival and phenotypic maintenance markers of cardiomyocytes in materials. Results: The results of HE staining, oil red O staining and DAPI fluorescence staining showed that there was no significant cell debris, nucleus and lipid residue in the prepared ECM hydrogel. The Sirius red staining and Alcian blue staining showed that the hydrogel retained collagen and glycolaminoglycan, which were the main components of ECM. The prepared hydrogel behaves as a viscous liquid at 4 â and as a gel state at 37 â. Scanning electron microscope results showed that the microstructure of the hydrogel was composed of irregular fibers and pores of different sizes. Under the guidance of ultrasound, the prepared ECM hydrogel could be successfully injected into the myocardium of mice. Immediately after the injection, the hyperechoic signal could be observed under ultrasound, suggesting that the hydrogel remained in the myocardium. HE staining of myocardial tissue evidenced that there was lump of gel in the injection area. The differentiated hiPSC-CMs were co-cultured with the prepared ECM hydrogel, and the results of live/dead staining showed that most of the hiPSC-CMs in the hydrogel group and the control group were alive, dead cells were scanty. The results of CCK-8 test showed that the absorbance values of the two groups were similar (P>0.05). The results of phalloidin staining showed that hiPSC-CMs could extend normally when co-cultured with ECM hydrogel. The cell morphology of the hydrogel group was similar with that of the control group, and there was no statistically significant difference in the F-actin coverage area per cell between the two groups (P>0.05). Immunofluorescence staining of cardiomyocyte markers showed that there was no significant difference in the coverage area of α-actinin and connexin-43 (Cx-43) per field between the hydrogel group and the control group (both P>0.05), the quantitative results of DAPI staining showed that there was no statistically significant difference in the number of cells between the two groups (P>0.05). Meanwhile, the results of Western blot showed that the expression levels of α-actinin and Cx-43 in cardiomyocytes in the hydrogel group were similar as those in the control group (both P>0.05). Conclusions: These results show that preparation of the ECM hydrogel from porcine omentum is successful. The hydrogel has good biocompatibility and no obvious cytotoxicity. Besides, the hydrogel can support the survival of hiPSC-CMs in vitro and maintain its phenotype. These properties make it a promising injectable cardiac tissue engineering material.
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Células Madre Pluripotentes Inducidas , Animales , Diferenciación Celular , Células Cultivadas , Matriz Extracelular , Humanos , Hidrogeles , Ratones , Miocitos Cardíacos , PorcinosRESUMEN
OBJECTIVE: We aimed at identifying the predictive roles of Low-Density Lipoprotein Triglycerides (LDL-TG) for major adverse cardiovascular events (MACEs). PATIENTS AND METHODS: A longitudinal study in a routine health check-up population was performed with an average follow-up of 4.8 years. The participants involved in this study were 1680, from 2007 to 2009, and all had followed-up for all-cause mortality, cardiovascular disease mortality, and the development of MACEs. The demographic information and anthropometric parameters at baseline were recorded. The baseline and follow-up conventional lipid parameters were measured. We also examined the level LDL-TG, as well as the relationship between its level and MACEs. RESULTS: MACEs individuals were characterized by statistically higher baseline LDL-TG (17.22 ± 8.05 vs. 16.39 ±7.35 nmol/l, p = 0.017). The univariate regression for MACEs group indicated that the LDL-TG (b = 0.813, HR = 2.254, 95% CI: 1.454-3.494, p < 0.001), older age, sex and other factors were a significant risk for MACEs. Furthermore, in the adjusted Cox model showed that only higher baseline LDL-TG (b =0.512, HR = 1.669, 95% CI: 1.013-2.748, p = 0.044) and older age (b = 0.062, HR = 1.064, 95% CI: 1.034-1.094, p < 0.001, Table IV) were still predictors for MACEs. CONCLUSIONS: Higher baseline LDL-TG closely associated with MACEs and it is a moderate and independent predictive factor for MACEs.
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Enfermedades Cardiovasculares , LDL-Colesterol , Modelos de Riesgos Proporcionales , Humanos , Lipoproteínas LDL , Estudios Longitudinales , Pronóstico , Factores de Riesgo , TriglicéridosRESUMEN
UNLABELLED: Human natural killer (NK) cells, which can directly lyse porcine endothelial cells, play an important role in xenotransplantation. HLA-G is a nonclassical major histocompatibility complex (MHC) class I molecules that has been implicated in protecting susceptible target cells from lysis by NK cells. The objective was to study the effect of protecting porcine endothelial cells transfected with HLA-G1 from human NK cell lysis. METHODS: The recombinant expression vector pcDNA3-HLA-G1 was transfected into primary cultured porcine aortic endothelial cells (PAECs) by lipofection. Surface expression of HLA-G1 in transected PAECs was confirmed by an immunofluoresence technique. Peripheral blood mononuclear cells (PBMC) and NK cell line (NK92) were used as NK effects cells with pcDNA3-HLA-G1-transfected PAECs as targets in a MTT method using pcDNA3 transfection as a negative control. RESULTS: Expression of HLA-G1 on PAECs conferred significant protection against NK-mediated lysis. The rate of NK92 cytotoxicity was reduced to 41.5% +/- 14.0% from 75.3% +/- 10.5% in the control group (P < .01). Similarly the rate of the PBMC cytotoxicity among different donors (n = 7) was reduced to 45.4% +/- 12.1% in contrast to 74.6% +/- 11.2% in the control group (P < .05). CONCLUSIONS: HLA-G1 molecules can directly protect xenogeneic PAECs against attack by human NK cells. These results indicate that the expression of HLA-G1 on the porcine cell surface may provide a new approach to overcome NK-mediated immunity to xenografts.