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Background: The associations of neutrophil-percentage-to-albumin ratio (NPAR) level with all-cause and cardiovascular disease (CVD)-cause mortality among patients with hypertension remain unclear. This study aims to investigate the associations of NPAR level with all-cause and CVD-cause mortality among patients with hypertension. Methods: This prospective cohort study included 8,990 patients with hypertension who participated in the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2010. Multivariable Cox proportional hazards regression models were used to compute hazard ratios and 95% CIs for the associations of NPAR level with all-cause mortality and CVD-cause mortality. Restricted cubic spline analyses were used to examine the nonlinear association of NPAR level with all-cause mortality and CVD-cause mortality. Results: This cohort study included data from 8,990 participants in analysis. During 104,474 person-years of follow-up, 3,069 all-cause deaths and 1,449 CVD-cause deaths were documented. Nonlinear associations were observed for NPAR levels with risk of all-cause mortality and CVD-cause mortality among patients with hypertension. Compared with participants in T1 of NPAR, there was a significantly increased risk of all-cause mortality and CVD-cause mortality for participants in both T2 and T3 in the fully adjusted model (model 3). The corresponding HRs for all-cause mortality were 1.10 (95% CI, 0.98-1.22) and 1.63 (95% CI, 1.45-1.82). The corresponding HRs for CVD-cause mortality were 1.10 (95% CI, 0.99-1.23) and 1.63 (95% CI, 1.46-1.81). Conclusions: Elevated NPAR level was significantly associated with an increased risk of all-cause and CVD-cause mortality in adults with hypertension. NPAR may be clinically useful for predicting long-term health outcomes and mortality in hypertensive population.
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BACKGROUND: Total anomalous pulmonary venous connection (TAPVC) is a rare congenital heart disease characterized by the inability of all pulmonary veins to connect to the left atrium. Our previous bibliometric article summarized the characteristics of only the 100 most cited papers in TAPVC research. The purpose of this study was to use comprehensive bibliometric analysis to examine the development history, current status, and future trends in the field of TAPVC. METHODS: All publications on TAPVC published between 2000 and 2023 were collected from the Web of Science Core Collection. The publication and citation data were quantitatively analyzed by publication year, country, institution, author, and journal. Co-authorship and co-occurrence analyses were performed using VOSviewer, and keyword and reference bursts were identified using CiteSpace. Pearson's test was used to examine the correlations between two continuous variables. RESULTS: As of July 20, 2023, we identified 368 publications with 3320 citations. These publications were published in 132 journals and authored by 1835 researchers from 457 institutions in 47 countries. For the number of publications, the top country, top institution, top author, and top journals were the United States (n = 82), Shanghai Jiao Tong University (n = 13), Huiwen Chen (n = 9), and Annals of Thoracic Surgery and Pediatric Cardiology (n = 29 each), respectively. For the number of citations, the top country, top affiliation, top author, and top journal were the United States (n = 1348), University of Toronto (n = 250), Christopher A. Caldarone (n = 315), and Annals of Thoracic Surgery (n = 746), respectively. The number of national publications significantly correlated with GDP (R = 0.887, P < 0.001), research & development (R&D) expenditure (R = 0.375, P = 0.013), population (R = 0.694, P < 0.001), and journals (R = 0.751, P < 0.001). The number of national citations significantly correlated with GDP (R = 0.881, P < 0.001), R&D expenditure (R = 0.446, P = 0.003), population (R = 0.305, P = 0.037), and journals (R = 0.917, P < 0.001). International collaboration in the field of TAPVC was not well developed. The most commonly cited publication discussed era changes in mortality and reoperation rate in TAPVC patients. The most common keywords were "total anomalous pulmonary venous connection" and "congenital heart disease". The keyword "case report" appeared most recently, with an average occurrence year of 2021.8. The co-occurrence analysis grouped 26 keywords into six themes: surgical repair of TAPVC, postoperative pulmonary vein stenosis, surgical repair of TAPVC patients with heterotaxy, application of echocardiography in diagnosing TAPVC, application of echocardiography in the prenatal diagnosis of TAPVC, and application of the sutureless technique in the surgical repair of TAPVC patients with right atrial isomerism or a single ventricle. Citation burst detection identified 32 references with citation bursts, seven of which had ongoing citation bursts until 2023. CONCLUSIONS: This study conducted a bibliometric analysis to provide a comprehensive overview of TAPVC research. We hope to offer new ideas for promoting development in the field of TAPVC.
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Bibliometría , Síndrome de Cimitarra , Humanos , Síndrome de Cimitarra/cirugía , Investigación Biomédica/tendenciasRESUMEN
BACKGROUND: Inter-leg systolic blood pressure difference (ILSBPD) has emerged as a novel cardiovascular risk factor. This study aims to investigate the predictive value of ILSBPD on all-cause and cardiovascular mortality in general population. METHODS: We combined three cycles (1999-2004) of the National Health and Nutrition Examination Survey (NHANES) data. Levels of ILSBPD were calculated and divided into four groups based on three cut-off values of 5, 10 and 15mmHg. Time-to-event curves were estimated with the use of the Kaplan-Meier method, and two multivariable Cox proportional hazards regression models were conducted to assess the hazard ratios (HRs) and 95% confidence intervals (CIs) of all-cause and cardiovascular mortality associated with ILSBPD. RESULTS: A total of 6 842 subjects were included, with the mean (SD) age of 59.5 (12.8) years. By December 31, 2019, 2 544 and 648 participants were identified all-cause and cardiovascular mortality respectively during a median follow-up of 16.6 years. Time-to-event analyses suggested that higher ILSBPD was associated with increased all-cause and cardiovascular mortality (logrank, p < 0.001). Every 5mmHg increment of ILSBPD brings about 5% and 7% increased risk of all-cause and cardiovascular mortality, and individuals with an ILSBPD ≥ 15mmHg were significantly associated with higher incidence of all-cause mortality (HR 1.43, 95%CI 1.18-1.52, p < 0.001) and cardiovascular mortality (HR 1.73, 95%CI 1.36-2.20, p < 0.001) when multiple confounding factors were adjusted. Subgroup and sensitivity analysis confirmed the relationship. CONCLUSIONS: Our findings suggest that the increment of ILSBPD was significantly associated with higher risk of all-cause and cardiovascular mortality in general population.
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Enfermedades Cardiovasculares , Humanos , Persona de Mediana Edad , Presión Sanguínea/fisiología , Encuestas Nutricionales , Enfermedades Cardiovasculares/epidemiología , Pierna , Factores de RiesgoRESUMEN
Air pollution is an important public health problem that endangers human health. However, the casual association and pathogenesis between particles < 2.5 µm (PM2.5) and hyperlipidemia remains incompletely unknown. Mendelian randomization (MR) and transcriptomic data analysis were performed, and an air pollution model using mice was constructed to investigate the association between PM2.5 and hyperlipidemia. MR analysis demonstrated that PM2.5 is associated with hyperlipidemia and the triglyceride (TG) level in the European population (IVW method of hyperlipidemia: OR: 1.0063, 95%CI: 1.0010-1.0118, p = 0.0210; IVW method of TG level: OR: 1.1004, 95%CI: 1.0067-1.2028, p = 0.0350). Mest, Adipoq, Ccl2, and Pcsk9 emerged in the differentially expressed genes of the liver and plasma of PM2.5 model mice, which might mediate atherosclerosis accelerated by PM2.5. The studied animal model shows that the Paigen Diet (PD)-fed male LDLR-/- mice had higher total cholesterol (TC), TG, and CM/VLDL cholesterol levels than the control group did after 10 times 5 mg/kg PM2.5 intranasal instillation once every three days. Our study revealed that PM2.5 had causality with hyperlipidemia, and PM2.5 might affect liver secretion, which could further regulate atherosclerosis. The lipid profile of PD-fed Familial Hypercholesterolemia (FH) model mice is more likely to be jeopardized by PM2.5 exposure.
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BACKGROUND: Given the fat redistribution in later stages of life, how the associations between abdominal obesity and the risk of morbidity and mortality have changed with age have not been elucidated, especially for waist to height ratio (WHtR). OBJECTIVE: To compare the strength of association between obesity indices and chronic diseases at baseline, and the subsequent mortality risk among US adults. METHODS: We included 21 109 participants from National Health and Nutrition Examination Survey 1999-2014. We performed logistic regression and receiver operating curve analysis to examine the discriminatory power of obesity indicators on cardiometabolic diseases and cancer at baseline. Sex-stratified and age-stratified Cox models were constructed to explore the prospective association between obesity indices and all-cause, cardiovascular and cancer mortality. RESULTS: Elevated WHtR, elevated waist circumference (WC) and body mass index (BMI)-classified obesity are associated with higher odds of hypertension (OR: 1.37-2.13), dyslipidemia (OR: 1.06 to 1.75, all p<0.05) and diabetes (OR: 1.40-3.16, all p<0.05). WHtR had significantly better discriminatory power to predict cardiometabolic health than BMI, especially for diabetes (area under the curve: 0.709 vs 0.654). After multivariable adjustment, all obesity indicators are associated with lower risk of all-cause mortality among females aged ≥65 years (HR: 0.64 to 0.85), but the association was only significant for BMI when obesity indicators were mutually adjusted (HR: 0.79). CONCLUSIONS: WHtR and WC appeared to be the better indicators for cardiometabolic health than BMI. However, BMI had a stronger and inverse association with a greater risk of all-cause mortality among older females.
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Índice de Masa Corporal , Enfermedades Cardiovasculares/mortalidad , Neoplasias/mortalidad , Obesidad Abdominal , Circunferencia de la Cintura , Relación Cintura-Estatura , Anciano , Distribución de la Grasa Corporal , Factores de Riesgo Cardiometabólico , Diabetes Mellitus/epidemiología , Femenino , Humanos , Masculino , Mortalidad , Obesidad Abdominal/diagnóstico , Obesidad Abdominal/epidemiología , Obesidad Abdominal/metabolismo , Medición de Riesgo/métodos , Medición de Riesgo/estadística & datos numéricos , Factores de Riesgo , Estados Unidos/epidemiologíaRESUMEN
PURPOSE: The relationship between thigh circumference and all-cause and cause-specific mortality has not been consistent. We aimed to examine how thigh circumference associates with all-cause, cardiovascular, and cerebrovascular mortality among US adults. PATIENTS AND METHODS: This cohort study included 19,885 US adults who participated in the 1999-2006 National Health and Nutrition Examination Survey (NHANES) with thigh circumference being measured at baseline, and survival status was ascertained until 31 December 2015. We used Cox proportional hazards models to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CI) for mortality according to thigh circumference in quartiles. Kaplan-Meier survival curve and restricted cubic spline regression were performed to evaluate the prospective association. Finally, subgroup analyses by age, gender, body mass index (BMI), and medical history at baseline were conducted. RESULTS: During a median follow-up of 11.9 years, 3513 cases of death, 432 death cases due to cardiovascular disease, and 143 death cases due to cerebrovascular disease have occurred. Multivariate Cox regression indicated that every 1cm increase in thigh circumference was related to 4% and 6% decreased risk of all-cause mortality and cardiovascular mortality, respectively. Compared to the reference group, the highest quartile of thigh circumference significantly decreased all-cause mortality by 21% (HR 0.79, 95% CI 0.62-1.00, P<0.05). However, the association of thigh circumference with cerebrovascular mortality was not significant. BMI was a significant effect modifier among individuals with a BMI of less than 25 kg/m2 (P<0.0001). CONCLUSION: A low thigh circumference appears to be associated with increased risk of all-cause and cardiovascular mortality, but not cerebrovascular mortality.
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BACKGROUND: Although many studies have suggested the association between elevated blood pressure and atrial fibrillation (AF), how the relationship between systolic blood pressure (SBP) and AF differ by antihypertensive treatment has been unclear. Therefore, this study aimed to explore the relationship between SBP and AF in hypertensive patients with or without antihypertensive treatment. METHODS: This was a cross-sectional study that enrolled 7,808 hypertensive patients aged ≥18 years old in 2013 in Guangdong, China. AF was screened and diagnosed by rest 12-lead electrocardiogram (ECG) or by self-reported. Patients were categorized into 5 groups according to a 10 mmHg increment in SBP. We then performed logistic regression and restricted cubic spline regression to evaluate the relationship between SBP and AF. RESULTS: Out of 7,808 participants (women 52.9%, mean age 62.3 years), 78 cases of AF were identified. Both univariate and multivariate logistic regression illustrated that SBP associated with a lower chance of AF in all participants when SBP was treated as a continuous variable (P<0.05) or as a categorical variable (P for trend <0.001). Similar trend was found in patients with antihypertensive therapy (P for trend <0.001) but not for those without antihypertensive medications. CONCLUSIONS: Our findings suggested that higher SBP is associated with lower likelihood of AF among all hypertensive patients and participants with antihypertensive treatment.
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Fibrilación Atrial , Adolescente , Adulto , Fibrilación Atrial/tratamiento farmacológico , Presión Sanguínea , China , Estudios Transversales , Femenino , Humanos , Persona de Mediana Edad , Factores de RiesgoAsunto(s)
Presión Sanguínea/fisiología , Accidente Cerebrovascular Isquémico/etiología , Accidente Cerebrovascular Isquémico/fisiopatología , Anciano , Anciano de 80 o más Años , Antihipertensivos/uso terapéutico , Pueblo Asiatico , Isquemia Encefálica/tratamiento farmacológico , China/epidemiología , Estudios de Cohortes , Femenino , Humanos , Hipertensión/epidemiología , Hipertensión/fisiopatología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Accidente Cerebrovascular/tratamiento farmacológicoRESUMEN
Objectives: The relationship between selenium and all-cause mortality has been inconsistent from observational studies and clinical trials. The present study aimed to reveal the relationship between serum selenium and all-cause and cardiovascular disease (CVD) mortality and the potential gender differences.Methods: All participants were recruited from the 1999-2006 National Health and Nutrition Examination Survey (NHANES). Participants with available serum selenium data were followed up until 31 December 2015. Cox proportional hazards models were performed to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CI) for all-cause and CVD mortality according to baseline selenium level in quartiles. Multivariable-adjusted spline curves were performed to detect non-linearity in relationships.Results: There were 2,903 subjects (50.7% female) included in this study. The mean age was 61.9 ± 13.7 years, and the mean selenium levels were 136.4 ± 19.6 ug/L. A total of 858 (29.6%) cases of all-cause mortality and 126 (4.3%) CVD mortality occurred during the median follow-up duration of 10.2 years. On average, deceased participants had lower serum selenium levels, (135.1 ± 22.3 vs. 137.0 ± 18.4 ug/L; P = 0.02). Serum selenium was also lower in female than male (134.7 ± 19.7 vs. 138.2 ± 19.4 ug/L; P < 0.01). Comparing with the lowest quartile, participants with the highest selenium concentration had a lower risk for all-cause (HR: 0.60, 95%CI: 0.45, 0.78; P < 0.01, P for trend<0.01) and CVD mortality (HR: 0.73, 95%CI: 0.37, 1.43; P = 0.36, P for trend = 0.90). Selenium was significantly associated with all-cause and CVD mortality among both males and females, but only associated with CVD mortality in among females.Conclusion: This study demonstrated significant relationship between serum selenium and all-cause mortality in both genders, but the relationship with CVD mortality was only significant in females.
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Enfermedades Cardiovasculares/mortalidad , Selenio/sangre , Factores de Edad , Anciano , Glucemia , Presión Sanguínea , Índice de Masa Corporal , Enfermedades Cardiovasculares/sangre , Causas de Muerte , Comorbilidad , Femenino , Conductas Relacionadas con la Salud , Humanos , Lípidos/sangre , Masculino , Persona de Mediana Edad , Encuestas Nutricionales , Modelos de Riesgos Proporcionales , Factores de Riesgo , Factores Sexuales , Factores SocioeconómicosRESUMEN
BACKGROUND: It is uncertain how diastolic blood pressure (DBP) may associate with ischaemic stroke in elder patients with hypertension. We aimed to explore this relationship in a Chinese community. METHODS: A total of 3315 participants aged ≥60 years with essential hypertension were enrolled between January 2010 and December 2011, and being followed up until 31 December 2016. DBP levels were categorised into five groups (<60, 60-70, 70-80, 80-90 and ≥90 mm Hg), using 70-80 mm Hg as referent. We performed Cox regression analysis and subgroup analyses to evaluate the relationship between DBP and the incidence of ischaemic stroke. RESULTS: Among the 3315 participants, 44.49% were men and they were 71.4 years old on average. During a median follow-up period of 5.5 years, there were 206 onset cases of ischaemic stroke. The HRs for the first ischaemic stroke in the fully adjusted model were 1.32 (95% CI 0.73 to 2.40) for DBP <70 mm Hg, 1.50 (95% CI 1.13 to 2.73) for DBP between 80 and 89.9 mm Hg and 2.31 (95% CI 1.14 to 4.68) for DBP ≥90 mm Hg compared with DBP between 70 and 79.9 mm Hg (p=0.020 for trend). Subgroup and interaction analysis showed no significant findings. CONCLUSIONS: DBP had a non-linear association with the risk of ischaemic stroke among Chinese elderly patients with hypertension. DBP between 70 and 80 mm Hg may be an appropriate indicator for a lower stroke risk.
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Presión Sanguínea , Hipertensión/fisiopatología , Accidente Cerebrovascular Isquémico/epidemiología , Anciano , Antihipertensivos/uso terapéutico , Diástole , Femenino , Humanos , Hipertensión/tratamiento farmacológico , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Modelos de Riesgos ProporcionalesRESUMEN
BACKGROUND: Observational studies have suggested that selenium levels might associate with the risk of cardio-metabolic diseases, but how circulating selenium is related to dyslipidemia remains inconclusive. OBJECTIVES: To investigate the association of circulating selenium levels with lipid profiles and dyslipidemia among US adults. METHODS: Using the data collected from the National Health and Nutrition Examination Survey (NHANES 1999-2006), we performed multivariate logistic regression to examine the association of circulating selenium levels (in quartiles) with total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), non-HDL-C, and atherogenic index (AI). RESULTS: We included 2903 adults (49.3 % male) (average age: 61.9) for analysis. Circulating selenium had non-linear association with TC, LDL-C, HDL-C, and AI (all pâ¯<â¯0.05). When comparing with the lowest quartile, subjects with the highest quartile of circulating selenium (>147.00⯵g/L) had the higher odds of elevated TG (OR: 1.75, 95% CIâ¯=â¯1.14, 2.68), TC (OR: 2.47, 95% CIâ¯=â¯1.62, 3.76), LDL-C (OR: 2.52, 95% CIâ¯=â¯1.60, 3.96), non-HDL-C (OR: 2.17, 95% CIâ¯=â¯1.41, 3.33), AI (OR: 1.20, 95% CIâ¯=â¯0.73, 1.97) and low-HDL-C (OR: 2.10, 95% CIâ¯=â¯1.19, 3.72). Similar patterns were observed in subgroup analysis. CONCLUSIONS: Higher circulating selenium levels had non-linear association with lipid profiles and the increased odds of dyslipidemia.
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Dislipidemias/sangre , Encuestas Nutricionales , Selenio/sangre , Femenino , Humanos , Lípidos/sangre , Masculino , Persona de Mediana Edad , Análisis Multivariante , Oportunidad RelativaRESUMEN
BACKGROUND: The prognostic value of serum uric acid (SUA) for incident acute coronary syndrome (ACS) in hypertensive subjects is uncertain. Therefore, the present study examined the association between SUA and incident ACS in a large cohort of Chinese hypertensive adults. METHODS: This was a retrospective cohort study, which enrolled 5473 Chinese community-dwelling hypertensive patients from 1 January 2012 to 31 December 2012. Study outcomes were ACS events, and patients were followed until 31 December 2016. Cox regression analyses were conducted to determine adjusted HRs and 95% CIs for baseline SUA tertiles (low, middle and high group) and for men and women separately. RESULTS: A total of 5473 participants were included in the analysis (median follow-up was 4.5 years). Participants were divided into tertiles based on SUA levels. During follow-up, 9 (0.49%), 14 (0.77%) and 25 (1.37%) patients developed ACS in the lowest, middle and highest tertiles, respectively. When compared with the lowest tertile of SUA, the highest tertile of SUA was associated with ACS risk in all subjects and in men and women separately (HR: 2.62, 95% CI 1.14 to 7.01, p=0.0233; 2.15, 95% CI 1.08 to 6.04, p=0.021, and 3.49, 95% CI 1.25 to 7.74, p=0.017, respectively). CONCLUSIONS: Higher SUA levels were independently associated with an elevated risk of ACS incidence. The relationship between SUA levels and ACS in hypertensive patients was J-shaped.
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Síndrome Coronario Agudo/epidemiología , Hipertensión Esencial/epidemiología , Hiperuricemia/epidemiología , Ácido Úrico/sangre , Anciano , China/epidemiología , Hipertensión Esencial/sangre , Femenino , Humanos , Hiperuricemia/sangre , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Modelos de Riesgos ProporcionalesRESUMEN
Background: Ischemic stroke is a major public health problem and a main cause of death in China. However, how resting heart rate may associate with ischemic stroke among patients with hypertension remains unclear.Objective: To investigate the association between resting heart rate and ischemic stroke among elderlies with hypertension in China.Methods: We conducted a retrospective study of elderlies with hypertension who aged ≥60 years and were free from a stroke at baseline. Resting heart rate at baseline was treated as both continuous and categorical variable. Hazard ratios for ischemic stroke were estimated by multivariate Cox proportional hazards models.Results: A total of 3071 elderlies with hypertension [1369 (44.6%) men, an average age of 71.3 ± 7.1 years] were enrolled, and 182 cases of ischemic stroke occurred during a mean follow-up period of 5.5 years. Multivariate Cox regression showed that every 10 bpm increment in resting heart rate elevated the risk of ischemic stroke by 21% (95%CI: 1.05, 1.73; P = 0.018). After adjusting for confounders, resting heart rate ≥90 bpm significantly associated with the risk of ischemic stroke (HR: 1.35, 95% CI = 1.16, 2.78) when using the resting heart rate <60 bpm as a referent. Subgroup analysis showed that the relation between resting heart rate and risk of ischemic stroke was seem to be stronger in female (HR: 1.32 vs 1.11), those with uncontrolled hypertension (HR: 1.32 vs 1.12), people with combined diabetes and hypertension (HR: 1.31 vs 1.12), people with overweight (HR: 1.39 vs 1.02) and those who aged >75 (HR: 1.33 vs 1.11). Smoothing spline plots suggested the optimal resting heart rate for the lowest risk of ischemic stroke was between 60 and 80 bpm.Conclusions: In Chinese elderly hypertensive patients, elevated resting heart rate was an independent predictor of ischemic stroke, and the optimal resting heart rate was around 70 bpm.
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Isquemia Encefálica/epidemiología , Frecuencia Cardíaca/fisiología , Hipertensión/epidemiología , Accidente Cerebrovascular/epidemiología , Anciano , Anciano de 80 o más Años , Glucemia , Presión Sanguínea , Índice de Masa Corporal , China , Comorbilidad , Femenino , Humanos , Lípidos/sangre , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Factores de RiesgoRESUMEN
Previous studies indicated that let-7 enhances osteogenesis and bone formation of human adipose-derived mesenchymal stem cells (MSCs). We also have confirmed that let-7f-5p expression was upregulated during osteoblast differentiation in rat bone marrow-derived MSCs (BMSCs) and was downregulated in the vertebrae of patients with glucocorticoid (GC)-induced osteoporosis (GIOP). The study was performed to determine the role of let-7f-5p in GC-inhibited osteogenic differentiation of murine BMSCs in vitro and in GIOP in vivo. Here, we report that dexamethasone (Dex) inhibited osteogenic differentiation of BMSCs and let-7f-5p expression, while increasing the expression of transforming growth factor beta receptor 1 (TGFBR1), a direct target of let-7f-5p during osteoblast differentiation under Dex conditions. In addition, let-7f-5p promoted osteogenic differentiation of BMSCs, as indicated by the promotion of alkaline phosphatase (ALP) staining and activity, Von Kossa staining, and osteogenic marker expression (Runx2,Osx, Alp, and Ocn), but decreased TGFBR1 expression in the presence of Dex. However, overexpression of TGFBR1 reversed the upregulation of let-7f-5p during Dex-treated osteoblast differentiation. Knockdown of TGFBR1 reversed the effect of let-7f-5p downregulation during Dex-treated osteogenic differentiation of BMSCs. We also found that glucocorticoid receptor (GR) mediated transcriptional silencing of let-7f-5p and its knockdown enhanced Dex-inhibited osteogenic differentiation. Further, when injected in vivo, agomiR-let-7f-5p significantly reversed bone loss induced by Dex, as well as increased osteogenic marker expression (Runx2, Osx, Alp, and Ocn) and decreased TGFBR1 expression in bone extracts. These findings indicated that the regulatory axis of GR/let-7f-5p/TGFBR1 may be important for Dex-inhibited osteoblast differentiation and that let-7f-5p may be a useful therapeutic target for GIOP.
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Glucocorticoides/farmacología , MicroARNs/metabolismo , Osteoporosis/metabolismo , Receptor Tipo I de Factor de Crecimiento Transformador beta/metabolismo , Animales , Enfermedades Óseas Metabólicas/metabolismo , Diferenciación Celular/efectos de los fármacos , Ensayo de Inmunoadsorción Enzimática , Glucocorticoides/efectos adversos , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , MicroARNs/genética , Osteoblastos/efectos de los fármacos , Osteoblastos/metabolismo , Osteogénesis/efectos de los fármacos , Osteoporosis/inducido químicamente , Receptor Tipo I de Factor de Crecimiento Transformador beta/genéticaRESUMEN
Insulin-like growth factor-1 receptor (IGF-1R) is involved in both glucose and bone metabolism. IGF-1R signaling regulates the canonical Wnt/ß-catenin signaling pathway. In this study, we investigated whether the IGF-1R/ ß-catenin signaling axis plays a role in the pathogenesis of diabetic osteoporosis (DOP). Serum from patients with or without DOP was collected to measure the IGF-1R level using enzyme-linked immunosorbent assay (ELISA). Rats were given streptozotocin following a four-week high-fat diet induction (DOP group), or received vehicle after the same period of a normal diet (control group). Dual energy X-ray absorption, a biomechanics test, and hematoxylin-eosin (HE) staining were performed to evaluate bone mass, bone strength, and histomorphology, respectively, in vertebrae. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting were performed to measure the total and phosphorylation levels of IGF-1R, glycogen synthase kinase-3ß (GSK-3ß), and ß-catenin. The serum IGF-1R level was much higher in patients with DOP than in controls. DOP rats exhibited strikingly reduced bone mass and attenuated compression strength of the vertebrae compared with the control group. HE staining showed that the histomorphology of DOP vertebrae was seriously impaired, which manifested as decreased and thinned trabeculae and increased lipid droplets within trabeculae. PCR analysis demonstrated that IGF-1R mRNA expression was significantly up-regulated, and western blotting detection showed that phosphorylation levels of IGF-1R, GSK-3ß, and ß-catenin were enhanced in DOP rat vertebrae. Our results suggest that the IGF-1R/ß-catenin signaling axis plays a role in the pathogenesis of DOP. This may contribute to development of the underlying therapeutic target for DOP.
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Diabetes Mellitus Tipo 2/complicaciones , Osteoporosis/etiología , Receptor IGF Tipo 1/fisiología , beta Catenina/fisiología , Anciano , Animales , Densidad Ósea , Diabetes Mellitus Experimental/complicaciones , Femenino , Humanos , Masculino , Persona de Mediana Edad , Ratas , Transducción de Señal , EstreptozocinaRESUMEN
BACKGROUND: The magnitude and direction of association of low-density lipid cholesterol (LDL-C) with diabetes mellitus (DM) might differ by hypertensive status, but there is limited epidemiological evidence in China. METHODS: We examined the association between LDL-C levels and DM in 9892 participants with hypertension using logistic regression. Participants were stratified into three groups according to LDL-C levels (desirable, borderline high or high), then further divided into quartiles. Restricted cubic spline regression models, subgroup analysis and interaction tests were also conducted to evaluate the shape of association. RESULTS: After adjusting for covariates, lower LDL-C had a significant and inverse association with the likelihood of DM in all participants (OR: 0.944, 95% CI = 0.893, 0.998). In participants with desirable LDL-C concentrations (< 3.4 mmol/L), LDL-C protected against DM (OR = 1.240, 95% CI = 1.076, 1.429 per 1 mmol/L decrease). In participants with higher LDL-C concentrations (> 4.1 mmol/L), LDL-C increased the DM likelihood (OR = 1.536, 95% CI = 1.126, 2.096 per 1 mmol/L increase). Restricted cubic spline regression also found a U-shaped association between LDL-C levels and DM prevalence. CONCLUSIONS: There was a U-shaped association between LDL-C levels and DM in Chinese patients with hypertension.
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LDL-Colesterol/sangre , Diabetes Mellitus/sangre , Hipertensión/sangre , Anciano , Pueblo Asiatico , HDL-Colesterol/sangre , Estudios Transversales , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/etnología , Diabetes Mellitus/fisiopatología , Femenino , Humanos , Hipertensión/diagnóstico , Hipertensión/etnología , Hipertensión/fisiopatología , Masculino , Persona de Mediana Edad , Análisis de Regresión , Triglicéridos/sangreRESUMEN
BACKGROUND/AIMS: Plastrum testudinis extracts (PTE) show osteoprotective effects on glucocorticoid-induced osteoporosis in vivo and in vitro. However, the underlying molecular mechanism of PTE in promoting osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) is unclear. METHODS: BMSC proliferation was investigated using the Cell Counting Kit-8 assay. BMSC differentiation and osteogenic mineralization were assayed using alkaline phosphatase and Alizarin red staining, respectively. The mRNA expression levels of Let-7f-5p, Tnfr2, Traf2, Pi3k, Akt, ß-catenin, Gsk3ß, Runx2, and Ocn were measured using real time quantitative polymerase chain reaction. Protein levels of TNFR2, TRAF2, p-PI3K, p-AKT, p-ß-CATENIN, and p-GSK3ß were analyzed by western blotting. The functional relationship of Let-7f-5p and Tnfr2 was determined by luciferase reporter assays. RESULTS: The optimum concentration for PTE was 30 µg/ml. PTE significantly promoted BMSC osteogenic differentiation and mineralization after 7 and 14 days in culture, respectively. The combination of PTE and osteogenic induction exhibited significant synergy. PTE upregulated Let-7f-5p, ß-catenin, Runx2, and Ocn mRNA expression, and downregulated Tnfr2, Traf2, Pi3k, Akt, and Gsk3ß mRNA expression. PTE inhibited TNFR2, TRAF2, and p-ß-CATENIN protein expression, and promoted p-PI3K, p-AKT, and p-GSK3ß protein expression. In addition, Tnfr2 was a functional target of Let-7f-5p in 293T cells. CONCLUSIONS: Our results suggested that PTE may promote BMSC proliferation and osteogenic differentiation via a mechanism associated with the regulation of Let-7f-5p and the TNFR2/PI3K/AKT signaling pathway.
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Células de la Médula Ósea/metabolismo , Diferenciación Celular/efectos de los fármacos , Células Madre Mesenquimatosas/metabolismo , MicroARNs/biosíntesis , Osteogénesis/efectos de los fármacos , Fosfatidilinositol 3-Quinasas/biosíntesis , Proteínas Proto-Oncogénicas c-akt/biosíntesis , Receptores Tipo II del Factor de Necrosis Tumoral/biosíntesis , Transducción de Señal/efectos de los fármacos , Extractos de Tejidos/farmacología , Animales , Células de la Médula Ósea/citología , Femenino , Células Madre Mesenquimatosas/citología , Ratas , Ratas Sprague-DawleyRESUMEN
Osteoporotic vertebral fracture (OVF) is a worldwide health concern and lacks sufficient basic studies. Suitable animal models should be the foundation for basic study and treatment of OVF. There have been few studies on the development of animal models of osteoporotic vertebral bone defects. OVF models using various animal species should be developed to evaluate the therapeutic strategy in preclinical testing. We developed an OVF model in rats. Rat osteoporosis was induced by ovariectomy (OVX), and 3 months after OVX, a 3 mm diameter hemispheric vertebral bone defect was developed in lumbar vertebra 6 (L6). Sagittal plain X-rays of the rats, their bone quantity, bone microarchitecture, and histomorphology were analyzed: 3 months after OVX, rats showed significantly lower bone quantity, relative bone volume, and total volume bone mineral density. After the vertebral bone defect had developed for 16 weeks, no significant indication of self-healing could be observed from the sagittal plain X-rays, three-dimensional images, and histomorphology. These results indicate that the rat model of osteoporotic vertebral bone defect, induced by OVX and a 3 mm diameter hemispheric vertebral bone defect, can sufficiently mimic OVF patients in clinic and provide a sound basis for subsequent studies.
RESUMEN
BACKGROUND: Recent data have demonstrated that long-lived memory T cells are present in the human lung and can play significant roles in the pathogenesis of specific allergic and autoimmune diseases. However, most evidence has been obtained from mouse studies, and the potential roles of memory T cells in human allergic diseases, such as asthma, remain largely unknown. METHODS: Thirty-three asthmatics, 26 chronic obstructive pulmonary disease (COPD) patients, and 22 healthy volunteers were enrolled in this study. Peripheral blood mononuclear cells (PBMCs) were isolated from the peripheral blood, and cell surface staining (CD4, CD45RO, CRTH2, CD62L, and CCR7) was performed for the detection of memory CD4+ T cells in blood. After stimulation with interleukin-27 (IL-27) or IL-4 for 15 min, the STAT1/STAT6 phosphorylation of memory CD4+ T cells was measured separately by flow cytometric techniques. The cytokine-releasing profiles after 6 days of culture under neutralization, TH2, TH2 + lipopolysaccharide (LPS), and TH2 + house dust mite (HDM) conditions were detected by intracellular protein (IL-5, IL-17, and interferon (IFN)-γ) staining. Correlation analyses between the profile of memory CD4+ T cells and clinical characteristics of asthma were performed. RESULTS: The number of circulating memory CD4+ T (CD4+ Tm) cells in asthmatics was increased compared with that in the healthy subjects (48 ± 5.7 % vs. 32 ± 4.1 %, p < 0.05). Compared with COPD and healthy subjects, the phosphorylation of signal transducer and activator of transcription 1 (STAT1-py) was impaired in asthmatics, whereas the phosphorylation of signal transducer and activator of transcription 6 (STAT6-py) was slightly enhanced. This imbalance of STAT1-py/STAT6-py was attributed to TH2 memory cells but not non-TH2 memory cells in blood. The cytokine-releasing profiles of asthmatics was unique, specifically IL-5high, IL-17high, and IFN-rlow, compared with those of COPD patients and healthy subjects. The IL-17 production levels in CD4+ Tm cells are associated with disease severity and positively correlated with medication consumption in asthma. CONCLUSIONS: The long-lived, antigen-specific memory CD4+ T cells, rather than PBMCs or peripheral lymphocytes, might be the ideal T cell subset candidates for analyzing the endotype of asthma. Memory CD4+ T cells exhibiting a shift in STAT phosphorylation and specific cytokine-releasing profiles have the potential to facilitate the understanding of disease heterogeneity and severity, allowing the more personalized treatment of patients.
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Asma/inmunología , Citocinas/metabolismo , Memoria Inmunológica , Factores de Transcripción STAT/metabolismo , Linfocitos T CD4-Positivos , Estudios de Casos y Controles , Femenino , Humanos , Mediadores de Inflamación/metabolismo , Interleucina-17/metabolismo , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , Fosforilación , Enfermedad Pulmonar Obstructiva Crónica/inmunología , Células Th2/inmunologíaRESUMEN
Objective Tumor cells are able to support their malignant proliferation by changing metabolic models .Prostate cells rely much on lipid metabolism in which ATP-citrate lyase ( ACLY) plays a very important role .The aim of this research was to study the effects of downregulated ACLY on the cell proliferation , cycle distribution and apoptosis of androgen-independent prostate cancer cells DUl45. Methods DU145 cells were divided into two groups:the cells in experiment group were transfected with the small interfering RNA-mediated knockdown of ACLY , while the cells in control group were transfected with meaningless small interfering RNA.Cell counting Kit test ( CCK-8 ) was applied to detect the effects of the downregulation of ATP citrate lyase on the proliferation of DU145.Flow cytometry instrument was used to analyze the variation of cell cycle distribution and apoptosis rate between groups .Western blot was used to detect the change of intracellular Caspase-3 protein content. Results Western blot showed favorable effects of ACLY interference .Compared with control group , ACLY protein content significantly decreased in experiment group ( P0.05), while the percentage of G2 cells decreased and the percentage of S cells in-creased with most cell cycle blocking at G 0/G1 stage, which were of significant difference .Meanwhile the expression of apoptosis pro-tein Caspase-3 upregulated significantly . Conclusion ACLY is of vital significance to maintain the malignant proliferation of prostate cancer cells and its downregulation results in the inhibition of cell proliferation and the promotion of cell apoptosis .