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1.
JACC Cardiovasc Interv ; 16(12): 1503-1513, 2023 06 26.
Artículo en Inglés | MEDLINE | ID: mdl-37380233

RESUMEN

BACKGROUND: Patients with chronic kidney disease (CKD) undergoing coronary angiography (CAG) are at high risk of contrast-associated acute kidney injury (CA-AKI) and mortality. Therefore, there is a clinical need to explore safe, convenient, and effective strategies for preventing CA-AKI. OBJECTIVES: This study sought to assess whether simplified rapid hydration is noninferior to standard hydration for CA-AKI prevention in patients with CKD. METHODS: This multicenter, open-label, randomized controlled study was conducted across 21 teaching hospitals and included 1,002 patients with CKD. Patients were randomized to either simplified hydration (SH) (SH group, with normal saline from 1 hour before to 4 hours after CAG at a rate of 3 mL/kg/h) or standard hydration (control group, with normal saline 12 hours before and 12 hours after CAG at a rate of 1 mL/kg/h). The primary endpoint of CA-AKI was a ≥25% or 0.5-mg/dL rise in serum creatinine from baseline within 48 to 72 hours. RESULTS: CA-AKI occurred in 29 of 466 (6.2%) patients in the SH group and in 38 of 455 (8.4%) patients in the control group (relative risk: 0.8; 95% CI: 0.5-1.2; P = 0.216). In addition, the risk of acute heart failure and 1-year major adverse cardiovascular events did not differ significantly between the groups. However, the median hydration duration was significantly shorter in the SH group than in the control group (6 vs 25 hours; P < 0.001). CONCLUSIONS: In CKD patients undergoing CAG, SH is noninferior to standard hydration in preventing CA-AKI with a shorter hydration duration.


Asunto(s)
Lesión Renal Aguda , Insuficiencia Renal Crónica , Humanos , Angiografía Coronaria/efectos adversos , Solución Salina , Resultado del Tratamiento , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/prevención & control , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/diagnóstico
2.
J Ethnopharmacol ; 317: 116763, 2023 Dec 05.
Artículo en Inglés | MEDLINE | ID: mdl-37315646

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: As prevalent acute respiratory condition in clinical practice, acute lung injury has a quick start and severe symptoms which can harm patients physically. Chaihu Qingwen granules (CHQW) is a classic formula for the treatment of respiratory diseases. Clinical observation shows that CHQW has good efficacy in treating colds, coughs, and fevers. AIM OF THE STUDY: The aim of this study was to investigate the anti-inflammatory effect of CHQW on lipopolysaccharide (LPS)-induced acute lung injury (ALI) model in rats and to explore its potential mechanism, as well as to clarify its substance composition. MATERIALS AND METHODS: Male SD rats were randomly divided into the blank group, the model group, the ibuprofen group, the Lianhua Qingwen capsule group and the CHQW group (2, 4 and 8 g/kg, respectively). The LPS-induced acute lung injury (ALI) model in rats was established after pre-administration. The histopathological changes in the lung and the levels of inflammatory factors in bronchoalveolar lavage fluid (BALF) and serum of ALI rats were observed. The inflammation-related proteins toll-like receptor 4 (TLR4), inhibitory kappa B alpha (IκBα), phospho-IκBα (p-IκBα), nuclear-factor-kappa B (NF-κB), and NLR family pyrin domain containing 3(NLRP3) expression levels were measured by western blotting analysis and immunohistochemical analysis. The chemical composition of CHQW was identified by liquid chromatography-quadrupole-time of flight-mass spectrometry (LC-Q-TOF-MS). RESULTS: CHQW significantly ameliorated lung tissue pathological injury in LPS-induced ALI rats and decreased the release of inflammatory cytokines (interleukin-1ß, interleukin-17 and tumor necrosis factor-α) in BALF and serum. In addition, CHQW decreased the expression of TLR4, p-IκBα and NF-κB proteins, increased the level of IκBα, regulated the TLR4/NF-κB signaling pathway, and inhibited the activation of NLRP3. The chemical components of CHQW were analyzed by LC-Q-TOF-MS, and a total of 48 components were identified by combining information from the literature, mainly flavonoids, organic acids, lignans, iridoids and phenylethanoid glycosides. CONCLUSION: The results of this study showed that the pretreatment of CHQW had a strong protective effect on LPS-induced ALI in rats, reducing lung tissue lesions and decreasing inflammatory cytokines released in BALF and serum. The protective mechanism of CHQW may be related to the inhibition of the TLR4/NF-κB signaling pathway and NLRP3 activation. The main active ingredients of CHQW are flavonoids, organic acids, lignans, iridoids and phenylethanoid glycosides.


Asunto(s)
Lesión Pulmonar Aguda , FN-kappa B , Ratas , Masculino , Animales , FN-kappa B/metabolismo , Receptor Toll-Like 4/metabolismo , Inhibidor NF-kappaB alfa , Proteína con Dominio Pirina 3 de la Familia NLR , Lipopolisacáridos/farmacología , Ratas Sprague-Dawley , Pulmón , Lesión Pulmonar Aguda/inducido químicamente , Lesión Pulmonar Aguda/tratamiento farmacológico , Lesión Pulmonar Aguda/metabolismo , Citocinas/metabolismo , Flavonoides/farmacología , Flavonoides/uso terapéutico , Antiinflamatorios/efectos adversos , Glicósidos/farmacología
3.
Curr Psychol ; 41(8): 5631-5639, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-33046955

RESUMEN

To assess the psychological effects of the novel coronavirus disease (COVID-19) on medical staff and the general public. During the outbreak of COVID-19, an internet-based questionnaire included The Self-rating Depression Scale (SDS), Perceived Stress Scale (PSS-10), and Impact of Event Scale-Revised (IES-R) was used to assess the impact of the pandemic situation on the mental health of medical staff and general population in Wuhan and its surrounding areas. Among the 1493 questionnaires completed, 827 (55.39%) of these were men, and 422 (28.27%) of these were medical personnel. The results suggest that the outbreak of COVID-19 has affected individuals significantly, the degree of which is related to age, sex, occupation and mental illness. There was a significant difference in PSS-10 and IES-R scores between the medical staff and the general population. The medical staff showed higher PSS-10 scores (16.813 ± 4.87) and IES-R scores (22.40 ± 12.12) compared to members of the general population PSS-10 (14.80 ± 5.60) and IES-R scores (17.89 ± 13.08). However, there was no statistically significant difference between the SDS scores of medical staff (44.52 ± 12.36) and the general public (43.08 ± 11.42). In terms of the need for psychological assistance, 50.97% of interviewees responded that they needed psychological counseling, of which medical staff accounted for 65.87% and non-medical staff accounted for 45.10%. During the ongoing COVID-19 outbreak, great attention should be paid to the mental health of the population, especially medical staff, and measures such as psychological intervention should be actively carried out for reducing the psychosocial effects.

4.
Biochim Biophys Acta Mol Cell Res ; 1867(10): 118791, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32619649

RESUMEN

BACKGROUND: Osteoarthritis is caused by cartilage dysplasia and has fetal origin. Prenatal dexamethasone exposure (PDE) induced chondrodysplasia in fetal rats by inhibiting transforming growth factor ß (TGFß) signaling. This study aimed to determine the effect of dexamethasone on fetal cartilage development and illustrate the underlying molecular mechanism. METHODS: Dexamethasone (0.2 mg/kg.d) was injected subcutaneously every morning in pregnant rats from gestational day (GD) 9 to GD21. Harvested fetal femurs and tibias at GD21 for immunofluorescence and gene expression analysis. Fetal chondrocytes were treated with dexamethasone (100, 250 and 500 nM), endoplasmic reticulum stress (ERS) inhibitor, and ryanodine receptor 1 (RYR1) antagonist for subsequent analyses. RESULTS: In vivo, prenatal dexamethasone exposure (PDE) decreased the total length of the fetal cartilage, the proportion of the proliferation area and the cell density and matrix content in fetal articular cartilage. Moreover, PDE increased RYR1 expression and intracellular calcium levels and elevated the expression of ERS-related genes, while downregulated the TGFß signaling pathway and extracellular matrix (ECM) synthesis in fetal chondrocytes. In vitro, we verified dexamethasone significantly decreased ECM synthesis through activating RYR 1 mediated-ERS. CONCLUSIONS: PDE inhibited TGFß signaling pathway and matrix synthesis through RYR1 / intracellular calcium mediated ERS, which ultimately led to fetal dysplasia. This study confirmed the molecular mechanism of ERS involved in the developmental toxicity of dexamethasone and suggested that RYR1 may be an early intervention target for fetal-derived adult osteoarthritis.


Asunto(s)
Dexametasona/efectos adversos , Feto/metabolismo , Feto/patología , Osteocondrodisplasias/inducido químicamente , Osteocondrodisplasias/embriología , Canal Liberador de Calcio Receptor de Rianodina/metabolismo , Animales , Calcio/metabolismo , Cartílago Articular/embriología , Cartílago Articular/patología , Cartílago Articular/ultraestructura , Condrocitos/metabolismo , Condrocitos/patología , Estrés del Retículo Endoplásmico , Matriz Extracelular/metabolismo , Femenino , Masculino , Osteocondrodisplasias/patología , Embarazo , Efectos Tardíos de la Exposición Prenatal/patología , Ratas Wistar , Transducción de Señal , Factor de Crecimiento Transformador beta/metabolismo
5.
Biochem Pharmacol ; 175: 113918, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-32194056

RESUMEN

BACKGROUND: Dexamethasone is widely used in the treatment of joint diseases due to its anti-inflammatory properties. However, it can cause serious adverse effects. The anterior cruciate ligament (ACL) is an important stabilizer of the knee joint. However, the effect of dexamethasone treatment on the ACL is unclear. OBJECTIVE: This study aims to explore the effects of dexamethasone on ACL tissues and cells through in vitro and in vivo experiments. RESULTS: In vitro, we found that after treatment with dexamethasone, human ACL cell apoptosis was increased, type I collagen (COL1A1) content was decreased, mineralization related genes (ENPP1 and ANKH) and calcified nodules were increased, and endoplasmic reticulum stress (ERS) was enhanced. However, ERS inhibitors could significantly inhibit the increase in calcification and the decrease in COL1A1 induced by dexamethasone. In vivo, Wistar rats received the infra-articular injection with dexamethasone (0.5 mg/kg) for 8 weeks. We found that dexamethasone treatment decreased the COL1A1 content and increased the COL2A1 content in the ACL tissues of rats and that chondroid differentiation and mineralization occurred. Meanwhile, the expression of ERS-related proteins was increased. CONCLUSION: Dexamethasone increased the calcification of ACL cells and caused ACL degeneration through ERS, suggesting that long-term treatment with dexamethasone may cause adverse effects on ACL tissue and increase the risk of long-term rupture.


Asunto(s)
Ligamento Cruzado Anterior/efectos de los fármacos , Ligamento Cruzado Anterior/metabolismo , Antiinflamatorios/toxicidad , Calcio/metabolismo , Dexametasona/toxicidad , Estrés del Retículo Endoplásmico/efectos de los fármacos , Adulto , Animales , Ligamento Cruzado Anterior/patología , Células Cultivadas , Relación Dosis-Respuesta a Droga , Estrés del Retículo Endoplásmico/fisiología , Femenino , Humanos , Masculino , Ratas , Ratas Wistar , Adulto Joven
6.
Toxicol Lett ; 314: 18-26, 2019 Oct 10.
Artículo en Inglés | MEDLINE | ID: mdl-31299270

RESUMEN

Epidemiological investigations indicate that effects related to prenatal adverse environments on the organs of the offspring could continue to adulthood. This study intends to confirm that prenatal nicotine exposure (PNE) increases the susceptibility of osteoarthritis (OA) in the male offspring, and to explore the potential intrauterine programming mechanism. During pregnancy, rats were divided into a PNE group and a control group. After birth, rats were given a high-fat diet for 6 months and long-distance running for 6 weeks. The rats were euthanized at 18 months after birth (PM18) and on gestational day 20 (GD20), respectively. Knee joints were collected for histochemistry, immunohistochemistry, and quantitative polymerase chain reaction (qPCR) assays. Histological analyses and the Mankin's score showed increased cartilage destruction and accelerated OA progression in adult offspring from the PNE group. Immunohistochemistry results showed decreased expression of transforming growth factor beta (TGFß) signaling pathway. Furthermore, the expression of apoptosis factors (caspase-3 and caspase-8), inflammatory factors [interleukin (IL)-1, IL-6] and matrix degradation enzymes [matrix metalloproteinase (MMP)-3, MMP-13] were also significantly increased. Traced back to the intrauterine period, it was found that the number of chondrocytes and the contents of Col2A1 and aggrecan in the matrix in the PNE group were decreased. And, the expression of the TGFß signaling pathway was inhibited. These results suggested that PNE enhanced the susceptibility of OA in male elderly offspring rats by down-regulating TGFß signaling, which increased articular cartilage local inflammation, matrix degradation, and cell apoptosis. This study confirmed the developmental origin of OA, and clarified the congenital and the living environment impact on the occurrence and development of OA. Our findings provide a theoretical and experimental basis for OA early prevention.


Asunto(s)
Articulaciones/efectos de los fármacos , Nicotina/toxicidad , Agonistas Nicotínicos/toxicidad , Osteoartritis/inducido químicamente , Efectos Tardíos de la Exposición Prenatal , Transducción de Señal , Factor de Crecimiento Transformador beta/metabolismo , Factores de Edad , Agrecanos/metabolismo , Animales , Apoptosis/efectos de los fármacos , Caspasa 3/metabolismo , Caspasa 8/metabolismo , Condrocitos/efectos de los fármacos , Condrocitos/metabolismo , Condrocitos/patología , Condrogénesis/efectos de los fármacos , Colágeno Tipo II/metabolismo , Femenino , Edad Gestacional , Interleucina-1/metabolismo , Interleucina-6/metabolismo , Articulaciones/metabolismo , Articulaciones/patología , Masculino , Exposición Materna , Metaloproteinasa 13 de la Matriz/metabolismo , Metaloproteinasa 3 de la Matriz/metabolismo , Osteoartritis/metabolismo , Osteoartritis/patología , Embarazo , Ratas Wistar , Factores de Riesgo , Factores Sexuales
7.
Front Immunol ; 9: 1775, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30123216

RESUMEN

The thymic stromal lymphopoietin (TSLP)/TSLP receptor (TSLPR) axis is involved in multiple inflammatory immune diseases, including coronary artery disease (CAD). To explore the causal relationship between this axis and CAD, we performed a three-stage case-control association analysis with 3,628 CAD cases and 3,776 controls using common variants in the genes TSLP, interleukin 7 receptor (IL7R), and TSLPR. Three common variants in the TSLP/TSLPR axis were significantly associated with CAD in a Chinese Han population [rs3806933T in TSLP, Padj = 4.35 × 10-5, odds ratio (OR) = 1.18; rs6897932T in IL7R, Padj = 1.13 × 10-7, OR = 1.31; g.19646A>GA in TSLPR, Padj = 2.04 × 10-6, OR = 1.20]. Reporter gene analysis demonstrated that rs3806933 and rs6897932 could influence TSLP and IL7R expression, respectively. Furthermore, the "T" allele of rs3806933 might increase plasma TSLP levels (R2 = 0.175, P < 0.01). In a stepwise procedure, the risk for CAD increased by nearly fivefold compared with the maximum effect of any single variant (Padj = 6.99 × 10-4, OR = 4.85). In addition, the epistatic interaction between TSLP and IL33 produced a nearly threefold increase in the risk of CAD in the combined model of rs3806933TT-rs7025417TT (Padj = 3.67 × 10-4, OR = 2.98). Our study illustrates that the TSLP/TSLPR axis might be involved in the pathogenesis of CAD through upregulation of mRNA or protein expression of the referenced genes and might have additive effects on the CAD risk when combined with IL-33 signaling.


Asunto(s)
Enfermedad de la Arteria Coronaria/etiología , Enfermedad de la Arteria Coronaria/metabolismo , Citocinas/genética , Epistasis Genética , Regulación de la Expresión Génica , Interleucina-33/genética , Receptores de Citocinas/genética , Anciano , Alelos , Estudios de Casos y Controles , China , Enfermedad de la Arteria Coronaria/diagnóstico , Enfermedad de la Arteria Coronaria/mortalidad , Citocinas/sangre , Citocinas/metabolismo , Femenino , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Interleucina-33/metabolismo , Desequilibrio de Ligamiento , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Polimorfismo de Nucleótido Simple , Modelos de Riesgos Proporcionales , Receptores de Citocinas/metabolismo , Receptores de Interleucina-7/genética , Transducción de Señal , Linfopoyetina del Estroma Tímico
8.
Zhonghua Xin Xue Guan Bing Za Zhi ; 40(1): 3-7, 2012 Jan.
Artículo en Chino | MEDLINE | ID: mdl-22490625

RESUMEN

OBJECTIVE: To explore the relationship between genetic polymorphisms of CACNA1C that encoded the a1c subunit of the L-type calcium channel and the efficacy of calcium channel blocker (CCB, Nifedipine extended release tablet/20 mg/d) in essential hypertension (EH) patients of Han Chinese in Wenzhou. METHODS: For the enrolled 103 EH patients, Multiplex Polymerase Chain Reaction (Multi-PCR) and matrix assisted laser desorption ionization time of flight MS (MLDI-TOF MS) were performed to detect their genotypes (rs216008, rs1051375, rs2299661, rs10848683, rs215976), blood pressure (BP) after CCB monotherapy was compared among patients with different genotypes. RESULTS: (1) Blood pressure was significantly reduced in all patients post CCB (P < 0.05 vs. pre-CCB). (2) Diastolic blood pressure reduction was more significant in subjects with rs2299661 C/C genotype (wild genotype) than in subjects with rs2299661C/G and rs2299661G/G genotype (mutational genotype) [(12.46 ± 7.91) mm Hg (1 mm Hg = 0.133 kPa) vs. (7.22 ± 8.01) mm Hg and (5.93 ± 9.77) mm Hg, P < 0.05]. (3) Systolic blood pressure reduction was more significant in subjects with rs216008 C/C genotype (wild genotype) than in subjects with rs216008 C/T genotype (mutational genotype) [(20.60 ± 12.35) mm Hg vs. (13.62 ± 10.21) mm Hg, P < 0.05]. (4) Blood pressure reduction was similar between subjects with genotype of rs1051375, rs10848683 and rs215976. CONCLUSION: EH patients with wild genotype of rs2299661 and rs216008 in CACNA1C are more likely to be responders of CCB monotherapy.


Asunto(s)
Bloqueadores de los Canales de Calcio/uso terapéutico , Canales de Calcio Tipo L/genética , Hipertensión/tratamiento farmacológico , Hipertensión/genética , Polimorfismo de Nucleótido Simple , Adulto , Anciano , Pueblo Asiatico/genética , Femenino , Humanos , Masculino , Persona de Mediana Edad
9.
Nat Genet ; 43(4): 345-9, 2011 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-21378986

RESUMEN

Coronary artery disease (CAD) causes more than 700,000 deaths each year in China. Previous genome-wide association studies (GWAS) in populations of European ancestry identified several genetic loci for CAD, but no such study has yet been reported in the Chinese population. Here we report a three-stage GWAS in the Chinese Han population. We identified a new association between rs6903956 in a putative gene denoted as C6orf105 on chromosome 6p24.1 and CAD (P = 5.00 × 10⁻³, stage 2 validation; P = 3.00 × 10⁻³, P = 1.19 × 10⁻8 and P = 4.00 × 10⁻³ in three independent stage 3 replication populations; P = 4.87 × 10⁻¹², odds ratio = 1.51 in the combined population). The minor risk allele A of rs6903956 is associated with decreased C6orf105 mRNA expression. We report the first GWAS for CAD in the Chinese Han population and identify a SNP, rs6903956, in C6orf105 associated with susceptibility to CAD in this population.


Asunto(s)
Pueblo Asiatico/genética , Enfermedad de la Arteria Coronaria/genética , Alelos , Estudios de Casos y Controles , China , Cromosomas Humanos Par 6/genética , Femenino , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Humanos , Desequilibrio de Ligamiento , Masculino , Polimorfismo de Nucleótido Simple , ARN Mensajero/genética , Factores de Riesgo
10.
Phytother Res ; 24(3): 393-8, 2010 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-19653192

RESUMEN

Astragalus polysaccharide (APS), the main extract from the traditional Chinese medicinal herb Astragalus membranaceus, has been reported to benefit the treatment of immune-inflammatory diseases and metabolic disorders. In atherosclerotic plaques, proinflammatory cytokines exert adverse effects on lipids thereby aggravating atherosclerosis. Recent evidence shows that tumor necrosis factor-alpha (TNF-alpha) can down-regulate the expression of ATP-binding cassette transporter A1 (ABCA1), which plays a vital role in reverse cholesterol transport and determines the process of atherosclerosis. In the present study, the effects of APS on ABCA1 expression, cholesterol effluent rate and total cholesterol content of THP-1 derived foam cells exposed to TNF-alpha were investigated. Compared with the foam cells exposed to TNF-alpha, ABCA1 expression was promoted in the presence of APS. Consequently the cholesterol effluent rate increased and the total cholesterol content decreased significantly. TNF-alpha could enhance the activity of nuclear factor-kappa B (NF-kappaB) in the foam cells. This effect could be attenuated by APS. These findings suggest that APS could protect ABCA1 against the lesion of TNF-alpha in THP-1 derived foam cells, which may contribute to its antiatherosclerotic properties.


Asunto(s)
Transportadoras de Casetes de Unión a ATP/metabolismo , Planta del Astrágalo/química , Células Espumosas/efectos de los fármacos , Polisacáridos/farmacología , Factor de Necrosis Tumoral alfa/farmacología , Línea Celular Tumoral , Colesterol/análisis , Humanos , FN-kappa B/metabolismo
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