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OBJECTIVE: This study aimed to investigate the role of protein kinase D (PKD)1 in regulating the growth, apop-tosis, and drug sensitivity of the squamous carcinoma cell line SCC-25. METHODS: The SCC-25 cell line was transfected with either the control-shRNA or PKD1-shRNA plasmids. The stable transfected cells were selected, and the efficiency of PKD1 knockdown was detected by Western blot. The growth and apoptosis of SCC-25 were analyzed with a cell counting kit-8 (CCK8) and flow cytometry. The 50% inhibitory concentrations (IC50) of paclitaxel in the control and PKD1 knockdown cell lines were detected by CCK-8. The expression levels of Bax, Bcl-2, and P-gp were detected by Western blot. RESULTS: PKD1 was constitutively expressed and phosphorylated in various cancer cell lines. Inhibiting the expression of PKD1 in SCC-25 cells by RNA interference could inhibit the growth and promote the apoptosis of SCC-25 cells via downregulating Bcl-2 expression. Additionally, inhibiting PKD1 expression could downregulate the expression of P-gp, thereby decreasing both the IC50 and resistance index of paclitaxel. CONCLUSIONS: PKD1 plays an important role in regulating the biobehavior of SCC-25. It is a potential therapeutic target for oral squamous carcinoma.
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Carcinoma de Células Escamosas , Neoplasias de la Boca , Apoptosis , Línea Celular Tumoral , Proliferación Celular , HumanosRESUMEN
OBJECTIVE: The aim of this study was to investigate the effect of saliva of patients with chronic periodontitis (CPD) on the differentiation, activation, and secretion of osteoclast-maturing mediators of macrophages. METHODS: A total of 40 saliva samples were collected from healthy donors (n=20) and severe periodontitis patients (n=20). Peripheral blood mononuclear cells (PBMCs) and THP-1 monocyte line cells were challenged with 15% saliva for 5 days. The phenotype, surface marker, and phagocytosis of macrophages were analyzed by flow cytometry and microscopy. Osteoclast-maturing mediators were assayed by using enzyme-linked immunosorbent assay (ELISA) kits. RESULTS: When PBMCs were treated with CPD saliva for 5 days, 61.25%±11.33% of cells were transformed into large granular cells; 86.78%±13.69% of large granular cells were identified as CD14âºâºCD16⺠macrophages. When THP-1 cells were treated with CPD saliva, most cells attached to the bottom of cell culture plates, thereby exhibiting macrophage morphology and releasing additional osteoclast-maturing mediators. Furthermore, the phagocytosis of THP-1 cells considerably increased in the presence of CPD saliva (66.35%±9.67%) compared with medium control (33.33%±7.52%), or healthy saliva (40.71%±3.52%). CONCLUSIONS: Salivaâ¯from patients withâ¯CPD can induce macrophage differentiation, activateâ¯phagocytose microorganisms, and secrete osteoclast-maturing mediators.
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Leucocitos Mononucleares , Macrófagos , Periodontitis , Saliva , Diferenciación Celular , Humanos , Monocitos , Periodontitis/inmunologíaRESUMEN
Despite substantial progress in medical care, the morbidity rate of diabetic nephropathy (DN) remains high in patients with diabetes. Evidence suggests that connective tissue growth factor (CTGF) induced podocyte injury may contribute to DN and CTGF inhibition could reduce albuminuria. However, to date the mechanisms involved in the effect of CTGF on podocyte injury have not been fully understood. The aim of this study is to investigate the effects of therapeutic CTGF antibody on glomerular ß-catenin expression and podocyte epithelial-mesenchymal transition (EMT) in diabetic mice. C57BL/6J mice were randomly divided into three groups as the following: the control, DN, and DN treated by CTGF antibody group. DN was induced by a single intraperitoneal injection of streptozotocin and then CTGF antibody was administrated three times per week for 8 weeks. Urinary albumin excretion, mesangial proliferation and matrix deposition, and ß-catenin expression in glomeruli at mRNA and protein level were all increased in DN mice compared to that in the control. Besides, the development of EMT in podocytes from diabetic mice, demonstrated by the downregulation of nephrin and upregulation of desmin in glomeruli, was detected. Furthermore, blocking CTGF by specific antibody reduced albuminuria, prevented the overexpression of CTGF, as well as ß-catenin, in glomeruli and subsequently ameliorated podocyte EMT in DN mice. In summary, this study suggested that CTGF antibody protected podocytes against injury in DN mice by reducing ß-catenin overexpression and preventing podocyte EMT, which might provide new insight into the mechanism of CTGF inhibition in the treatment of DN. J. Cell. Biochem. 118: 3706-3712, 2017. © 2017 Wiley Periodicals, Inc.
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Anticuerpos/farmacología , Factor de Crecimiento del Tejido Conjuntivo/antagonistas & inhibidores , Nefropatías Diabéticas/prevención & control , Transición Epitelial-Mesenquimal , Glomérulos Renales/metabolismo , Podocitos/metabolismo , beta Catenina/biosíntesis , Animales , Factor de Crecimiento del Tejido Conjuntivo/metabolismo , Nefropatías Diabéticas/metabolismo , Nefropatías Diabéticas/patología , Glomérulos Renales/patología , Masculino , Ratones , Podocitos/patologíaRESUMEN
PGE2 exerts its biological effect through binding to various EP receptors that result inactivation of various signal transduction pathways. It also plays an important role in mice glomerular mesangial cells (MCs) damage induced by transforming growth factor-ß1 (TGF-ß1); however, the molecular mechanisms remain unknown. In the present study, we tested the efficacy of four selective agonists of PGE2 receptor, EP1A (17-phenyl trinor prostaglandin E2 ethyl amid), EP2A (butaprost), EP3A (sulprostone) and EP4A (cay10580), on mice MCs. Compared with the cAMP produced by TGF-ß1, additional pretreatment of EP3A decreased the cAMP level. MCs treated with EP1A and EP3A augmented PGE2, cyclooxygenase-2 (COX-2), membrane-bound PGE synthase 1 (mPGES1), laminin (LN), connective tissue growth factor (CTGF) and cyclin D1 expression stimulated by TGFß1. EP1A and EP3A increased the number of cells in S+G2/M phase and reduced cells in G0/G1 phase. EP1 and EP3 agonists also strengthened TGFß1-induced mitogen-activated protein kinase (p38MAPK) and extracellular-signal-regulated kinase 1/2 (ERK1/2) phosphorylation. Whereas MCs treated with EP2A and EP4A weakened PGE2, COX-2, mPGES1, LN, CTGF and cyclin D1 expression stimulated by TGFß1. EP2A and EP4A decreased the number of cells in S+G2/M phase and increased cells in G0/G1 phase. EP2 and EP4 agonists weakened TGFß1-induced p38MAPK and ERK1/2 phosphorylation. These findings suggest that PGE2 has an important role in the progression of kidney disease via the EP1/EP3 receptor, whereas EP2 and EP4 receptors are equally important in preserving the progression of chronic kidney failure. Thus, agonists of EP2 and EP4 receptors may provide a basis for treating kidney damage induced by TGF-ß1.
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Micro-inflammation plays an important role in the pathogenesis of spontaneously hypertensive rat (SHR). In the present study, we investigated the therapeutic potential of resveratrol (RSV), a polyphenol with anti-fibrosis activity in hypertensive renal damage model. In SHR renal damage model, RSV treatment blunted the increase in urine albumin excretion, urinary ß2-microglobulin (ß2-MG), attenuated the decrease in creatinine clearance rate (CCR). The glomerular sclerosis index (1.54±0.33 compared with 0.36±0.07) and tubulointerstitial fibrosis (1.57±0.31 compared with 0.19±0.04) were significantly higher in SHRs compared with Wistar Kyoto rats (WKYs), which were significantly lower by RSV treatment. The increases in mesangium accumulation and the expression of renal collagen type I (Col I), fibronectin (Fn), plasminogen activator inhibitor-1 (PAI-1) and transforming growth factor-ß1 (TGF-ß1) in SHR were also reduced by RSV treatment. Nuclear factor κB (NF-κB) expression was increased in the cytoplasm and nuclei of the SHR kidneys, which was significantly decreased by RSV treatment. Furthermore, the protein level of IκB-α significantly decreased in the kidneys of the SHR when compared with the WKYs. RSV treatment partially restored the decreased IκB-α level. In SHR kidney, increased expression of interleukin-6 (IL-6), intercellular adhesion molecule-1 (ICAM-1) and monocyte chemoattractant protein 1 (MCP-1) were observed. These changes were attenuated by RSV treatment. No changes in blood pressure were detected between SHR group and SHR + RSV group. Taken together, the present study demonstrated that RSV treatment may significantly attenuate renal damage in the SHR model of chronic kidney disease (CKD). The renal protective effect is associated with inhibition of IL-6, ICAM-1 and MCP-1 expression via the regulation of the nuclear translocation of NF-κB, which suggesting that micro-inflammation may be a potential therapeutic target of hypertensive renal damage.
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Fibrosis/tratamiento farmacológico , Hipertensión/tratamiento farmacológico , Inflamación/tratamiento farmacológico , Estilbenos/administración & dosificación , Lesión Renal Aguda/tratamiento farmacológico , Lesión Renal Aguda/genética , Lesión Renal Aguda/patología , Animales , Presión Sanguínea/efectos de los fármacos , Colágeno Tipo I/genética , Modelos Animales de Enfermedad , Fibronectinas/genética , Fibrosis/patología , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Hipertensión/genética , Hipertensión/patología , Inflamación/genética , Inflamación/patología , Riñón/efectos de los fármacos , Riñón/patología , Inhibidor 1 de Activador Plasminogénico/genética , Ratas , Resveratrol , Factor de Crecimiento Transformador beta1/genética , Microglobulina beta-2/genéticaRESUMEN
OBJECTIVES: To determine the role of high mobility group chromosomal protein N2 (HMGN2) in the development of periodontitis plaque biofilm. METHODS: Saliva samples were collected before clinical interventions in patients with periodontitis (25 Mild periodontitis, 25 Moderate periodontitis and 25 Severe periodontitis) and healthy controls ( n=25).Following an estimation of dental plaque index, the level of HMGN2 in saliva was determined by enzyme-linked immunosorbent assay (ELISA).The recombinant human HMGN2 protein was purified and tested, its inhibitive effects on Porphyromonas gingivalis (P.g)growth and formation of P.g bioflim were detected by K-B antibacterial annulus and crystal violet staining, respectively. RESULTS: The healthy controls had lower levels of HMGN2 in saliva than those with periodontitis, especially those with severe periodontitis ( P<0.01).The level of HMGN2 was negatively correlated with dental plaque index ( r=-0.363, P<0.05). HMGN2 inhibited the development of main periodontal bacteria biofilm ( P<0.05). CONCLUSIONS: HMGN2 is involved in the development of periodontitis plaque biofilm and plays an important role in the development of periodontitis.
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Placa Dental/metabolismo , Proteína HMGN2/metabolismo , Periodontitis/metabolismo , Saliva/metabolismo , Estudios de Casos y Controles , Humanos , Porphyromonas gingivalisRESUMEN
OBJECTIVES: To explore the effects of the Smoothened (Smo) inhibitor PF-5274857 on cigarette smoke (CS)-induced epithelial-mesenchymal transition (EMT) and apply a new idea fororal squamous cell carcinoma (OSCC) treatment. METHODS: Beas-2b cells were used to investigate the CS-induced EMT. Both pretreat and post-treat were performed in the study. In pretreat group, after being pretreated with 3 µmol/L PF-5274857 for 2 h, cells were cultured with CS for 8 d; In post-treat group, cells were treated by 3 µmol/L PF-5274857 for 4 d after CS cultrue. Western blot and immunofluorescence were applied to examine the EMT markers E-cadherin, vimentin, and smooth muscle actin α (α-SMA) in Beas-2b epithelial cells. The transwell culture system was used in migration assays. RESULTS: Pretreat Beas-2b cells with PF-5274857 for 2 h can prevent the CS-induced EMT for epithelial and mesenchymal markers, as well as migration capacity. Up regulated E-cadherin and down regulated vimentin and α-SMA were observed by Western blot. Furthermore Beas-2b cells induced by CS that underwent EMT showed increased E-cadherin and decreased vimentin and α-SMA after treatment with PF-5274857 for 4 d. Importantly, the elevated migration capacity level was also decreased. CONCLUSIONS: The Smo inhibitor PF-5274857 has both preventive effect and therapeutic potential against CS-induced EMT.
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2,2'-Dipiridil/análogos & derivados , Células Epiteliales/citología , Transición Epitelial-Mesenquimal , Piperazinas/farmacología , Humo/efectos adversos , 2,2'-Dipiridil/farmacología , Cadherinas , Línea Celular , Células Epiteliales/efectos de los fármacos , Humanos , Productos de Tabaco/efectos adversosRESUMEN
The prostaglandin E2 receptor, EP2 (E-prostanoid 2), plays an important role in mice glomerular MCs (mesangial cells) damage induced by TGFß1 (transforming growth factor-ß1); however, the molecular mechanisms for this remain unknown. The present study examined the role of the EP2 signalling pathway in TGFß1-induced MCs proliferation, ECM (extracellular matrix) accumulation and expression of PGES (prostaglandin E2 synthase). We generated primary mice MCs. Results showed MCs proliferation promoted by TGFß1 were increased; however, the production of cAMP and PGE2 (prostaglandin E2) was decreased. EP2 deficiency in these MCs augmented FN (fibronectin), Col I (collagen type I), COX2 (cyclooxygenase-2), mPGES-1 (membrane-associated prostaglandin E1), CTGF (connective tissue growth factor) and CyclinD1 expression stimulated by TGFß1. Silencing of EP2 also strengthened TGFß1-induced p38MAPK (mitogen-activated protein kinase), ERK1/2 (extracellular-signal-regulated kinase 1/2) and CREB1 (cAMP responsive element-binding protein 1) phosphorylation. In contrast, Adenovirus-mediated EP2 overexpression reversed the effects of EP2-siRNA (small interfering RNA). Collectively, the investigation indicates that EP2 may block p38MAPK, ERK1/2 and CREB1 phosphorylation via activation of cAMP production and stimulation of PGE2 through EP2 receptors which prevent TGFß1-induced MCs damage. Our findings also suggest that pharmacological targeting of EP2 receptors may provide new inroads to antagonize the damage induced by TGFß1.
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Células Mesangiales/efectos de los fármacos , Subtipo EP2 de Receptores de Prostaglandina E/metabolismo , Transducción de Señal , Factor de Crecimiento Transformador beta/farmacología , Animales , Western Blotting , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Factor de Crecimiento del Tejido Conjuntivo/genética , Factor de Crecimiento del Tejido Conjuntivo/metabolismo , AMP Cíclico/metabolismo , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Ciclina D1/genética , Ciclina D1/metabolismo , Ciclooxigenasa 2/genética , Ciclooxigenasa 2/metabolismo , Dinoprostona/metabolismo , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Expresión Génica , Oxidorreductasas Intramoleculares/genética , Oxidorreductasas Intramoleculares/metabolismo , Células Mesangiales/metabolismo , Ratones Endogámicos C57BL , Fosforilación , Cultivo Primario de Células , Prostaglandina-E Sintasas , Interferencia de ARN , Subtipo EP2 de Receptores de Prostaglandina E/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoRESUMEN
Roles of the prostaglandin E2 E-prostanoid 4 receptor (EP4) on extracellular matrix (ECM) accumulation induced by TGF-ß1 in mouse glomerular mesangial cells (GMCs) remain unknown. Previously, we have identified that TGF-ß1 stimulates the expression of FN and Col I in mouse GMCs. Here we asked whether stimulation of EP4 receptors would exacerbate renal fibrosis associated with enhanced glomerular ECM accumulation. We generated EP4(Flox/Flox) and EP4(+/-) mice, cultured primary WT, EP4(Flox/Flox) and EP4(+/-) GMCs, AD-EP4 transfected WT GMCs (EP4 overexpression) and AD-Cre transfected EP4(Flox/Flox) GMCs (EP4 deleted). We found that TGF-ß1-induced cAMP and PGE2 synthesis decreased in EP4 deleted GMCs and increased in EP4 overexpressed GMCs. Elevated EP4 expression in GMCs augmented the coupling of TGF-ß1 to FN, Col I expression and COX2/PGE2 signaling, while TGF-ß1 induced FN, Col I expression and COX2/PGE2 signaling were down-regulated in EP4 deficiency GMCs. 8 weeks after 5/6 nephrectomy (Nx), WT and EP4(+/-) mice exhibited markedly increased accumulation of ECM compared with sham-operated controls. Albuminuria, blood urea nitrogen and creatinine (BUN and Cr) concentrations were significantly increased in WT mice as compared to those of EP4(+/-) mice. Urine osmotic pressure was dramatically decreased after 5/6 Nx surgery in WT mice as compared to EP4(+/-) mice. The pathological changes in kidney of EP4(+/-) mice was markedly alleviated compared with WT mice. Immunohistochemical analysis showed significant reductions of Col I and FN in the kidney of EP4(+/-) mice compared with WT mice. Collectively, this investigation established EP4 as a potent mediator of the pro-TGF-ß1 activities elicited by COX2/PGE2 in mice GMCs. Our findings suggested that prostaglandin E2, acting via EP4 receptors contributed to accumulation of ECM in GMCs and promoted renal fibrosis.
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Células Mesangiales/metabolismo , Subtipo EP4 de Receptores de Prostaglandina E/metabolismo , Albuminuria/metabolismo , Animales , Nitrógeno de la Urea Sanguínea , Creatinina/metabolismo , Ciclooxigenasa 2/metabolismo , Dinoprostona/metabolismo , Matriz Extracelular/metabolismo , Enfermedades Renales/metabolismo , Glomérulos Renales/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Nefrectomía/métodos , Presión Osmótica/fisiología , Transducción de Señal/fisiología , Factor de Crecimiento Transformador beta1/metabolismoRESUMEN
OBJECTIVE: To investigate changes of adiponectin and its receptors (Adipo R) in rats following chronic renal failure. METHODS: Male SD rats were randomly divided into two groups: control group and chronic renal failure (CRF) group. The CRF group were gavaged with adenine (300 mg/kg/d) for 4 weeks and the control group with drinking water. All rats were anesthetized at 2nd or 4th week and blood and urine samples were collected for detection of renal function, 24 h urine protein and adiponectin concentration. Renal tissues were also collected for HE staining, immunohistochemistry and RT-PCR screening. RESULTS: Compared with control group, the serum concentrations of urea and creatinine, 24 h urine protein excretion in the CRF group were significantly higher at 2nd week and further increased at 4th week (p < 0.05). The adiponectin levels in serum and urine in the CRF group were significantly higher than those of control group (p < 0.01). The renal expressions of Adipo R1 and Adipo R2 in CRF group were also significantly increased compared to control group (p < 0.01). The increased expressions of Adipo R1 and Adipo R2 were positively related to the adiponectin levels in serum, urine, and 24 h urine protein. CONCLUSION: The significant changes in expression of adiponectin and its receptors in rat CRF model could be an adaptive response that may provide the basis to understand pathological changes in chronic kidney disease.
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Adiponectina/sangre , Fallo Renal Crónico/sangre , Riñón/metabolismo , Receptores de Adiponectina/metabolismo , Adiponectina/orina , Animales , Riñón/patología , Fallo Renal Crónico/patología , Pruebas de Función Renal , Masculino , ARN Mensajero/metabolismo , Distribución Aleatoria , RatasRESUMEN
BACKGROUND: Serum phosphorus control is critical for chronic kidney disease (CKD) 5D patients. Currently, clinical profile for an oral phosphorus binder in the mainland Chinese population is not available. OBJECTIVE: To establish the efficacy, safety, and tolerability of lanthanum carbonate in CKD 5D patients. DESIGN: Multicenter, randomized, double blind, placebo-controlled study. A central randomization center used computer generated tables to allocate treatments. SETTING: Twelve tertiary teaching hospitals and medical university affiliated hospitals in mainland China. PARTICIPANTS: Overall, 258 hemodialysis or continuous ambulatory peritoneal dialysis (CAPD) adult patients were enrolled. INTERVENTION: After a 0-3-week washout period and a 4-week lanthanum carbonate dose-titration period, 230 patients were randomized 1:1 to receive lanthanum carbonate (1500 mg-3000 mg) or placebo for a further 4-week maintenance phase. MAIN OUTCOME MEASURES: Efficacy and safety of lanthanum carbonate to achieve and maintain target serum phosphorus concentrations were assessed. RESULTS: In the titration phase, serum phosphorus concentrations of all patients decreased significantly. About three-fifths achieved target levels without significantly disturbing serum calcium levels. At the end of the maintenance period, the mean difference in serum phosphorus was significantly different between the lanthanum carbonate and placebo-treated groups (0.63±0.62 mmol/L vs. 0.15±0.52 mmol/L, P < 0.001). The drug-related adverse effects were mild and mostly gastrointestinal in nature. CONCLUSION: Lanthanum carbonate is an efficacious and well-tolerated oral phosphate binder with a mild AE profile in hemodialysis and CAPD patients. This agent may provide an alternative for the treatment of hyperphosphatemia in CKD 5D patients in mainland China. TRIAL REGISTRATION: No. ChiCTR-TRC-10000817.
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Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Hiperfosfatemia/tratamiento farmacológico , Hiperfosfatemia/epidemiología , Lantano/administración & dosificación , Insuficiencia Renal Crónica/tratamiento farmacológico , Insuficiencia Renal Crónica/epidemiología , Adolescente , Adulto , Anciano , China/epidemiología , Comorbilidad , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Medición de Riesgo , Resultado del Tratamiento , Adulto JovenRESUMEN
OBJECTIVE: The aim of this study was to investigate the association of Glycoprotein IIb (GPIIb) human platelet antigen-3 (HPA-3) a/b polymorphism with end-stage renal disease (ESRD) on hemodialysis (HD) and native Arteriovenous fistula (AVF) thrombosis. METHODS: The polymorphism in the GPIIb subunit of the receptor HPA-3 (a and b alleles) was identified by polymerase chain reaction with sequence-specific primers (PCR-SSP) in 145 HD patients and 120 healthy controls from a Chinese Han population. The HD patients were classified into two groups: G1 and G2. G1 included 65 HD patients presented at least one AVF thrombosis episode and G2 included 80 HD patients without any episode of AVF thrombosis. RESULTS: There were no significant differences in either HPA-3 a/b genotypes (aa, ab, and bb) frequency distribution (p = 0.396) or allele (a and b) frequency distribution (p = 0.146) between HD patients and control groups. However, there were significant differences in both HPA-3 a/b genotypes (aa, ab, and bb) distribution (χ(2) = 6.127, p = 0.047) and allele (a and b) frequency distribution (χ(2) = 5.954, p = 0.015) between G1 and G2. The relative risk of native AVF dysfunction in ab + bb patients compared with that of aa patients was 2.31 (95% confidence interval: 1.18-4.52). CONCLUSIONS: These findings suggest an association between AVF thrombosis and the HPA-3b allele, and it is likely that HPA-3 a/b polymorphisms could be useful markers for potential risk of native AVF thrombosis in HD patients.
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Derivación Arteriovenosa Quirúrgica , Fallo Renal Crónico/genética , Glicoproteína IIb de Membrana Plaquetaria/genética , Polimorfismo Genético , Diálisis Renal/efectos adversos , Trombosis/genética , Adulto , Femenino , Humanos , Fallo Renal Crónico/terapia , Masculino , Persona de Mediana Edad , Factores de Riesgo , Trombosis/etiologíaRESUMEN
AIM: To describe the rates and patterns of unintentional injuries among primary and middle school students in China. METHODS: A cross-sectional survey was conducted in Maanshan City of the Anhui Province in eastern China. All students attending six primary and four middle schools, selected randomly, were asked to report unintentional injuries occurring in the 12-mo period before the survey. The occurrence of unintentional injuries that resulted in medical attendance was summarized by study grade, sex, month and external causes. RESULTS: The annual event-based injury rate per 100 students was higher among boys (21.7) than girls (17.6). Only 1.9% of the episodes resulted in hospitalization, and 17.8% resulted in missing school. The most frequent injuries were falls (38.2%) and transportation-related injuries (19.6%). The risk of injury was lower in middle schools than primary schools. Distribution by month of occurrence showed two peaks in boys during spring and autumn, but no clear peak was observed in girls. CONCLUSION: The descriptive epidemiology of unintentional injuries among students in China provides useful information on the distributions in person, place and time, which in turn provide hints for the further exploration of possible risk factors that are important in planning strategies for future prevention.
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Accidentes/estadística & datos numéricos , Salud Urbana , Heridas y Lesiones/epidemiología , Adolescente , Distribución por Edad , Niño , China/epidemiología , Estudios Transversales , Femenino , Humanos , Masculino , Estaciones del Año , Distribución por Sexo , Índices de Gravedad del TraumaRESUMEN
OBJECTIVE: To describe the rate and pattern of unintentional school injuries among primary and middle school students and to explore the major risk factors involved. STUDY DESIGN: A cross-sectional survey of more than 10,000 students attending 6 primary and 4 middle schools selected randomly from all schools in Maanshan City of Anhui Province in eastern China was conducted to collect information on school injuries occurring in the 12-month period before the survey. Rate ratios for risk factors were estimated using the negative binomial regression analysis. RESULTS: The annual person-based school injury rate was 5.22 (95% CI: 3.90-6.53) percent. The annual event-based injury rate was 5.40 (95% CI: 4.04-6.76) per 100 students. Most injuries in school were relatively mild and only 1.53% (9/590) of the episodes resulted in hospitalization. The most frequent injures were falls (73%), and the most commonly injured sites were the upper limbs (46%). Male sex, primary school grades, poor health status, poor ability to concentrate, bad risk-taking behavior and high study-related stress were important risk factors. CONCLUSION: This study provided useful baseline information on school injuries in China and identified important risk factors that would be important in planning prevention strategies.
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Prevención de Accidentes , Estudiantes/estadística & datos numéricos , Heridas y Lesiones/epidemiología , Adolescente , Niño , China/epidemiología , Estudios Transversales , Femenino , Humanos , Incidencia , Masculino , Análisis Multivariante , Análisis de Regresión , Factores de Riesgo , Heridas y Lesiones/etiología , Heridas y Lesiones/prevención & controlRESUMEN
OBJECTIVE: To probe into the effects of familial factors on injury-related behaviors in children. METHODS: Injury-related behaviors and familial factors of 6884 children were investigated with Family Questionnaire and Child Behavior Checklist. Multi-nominal logistic regression analysis was performed. RESULTS: There were 1670 (24.26%) children having serious injury-related behaviors and 3683 (53.50%) children having moderate injury-related behaviors. Factors contributing to children's injury-related behaviors would include punishment or indifference as well as the mode of parents' education; reintegral type of family; the level of parents' cognition on injuries; unfit location of medicine at home and careless attitudes of parents. CONCLUSION: There was close relationship between children's injury-related behaviors and familial factors. To avoid injury-related behaviors and to prevent injury occurrence, the importance of familial factors must be stressed.
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Conducta Infantil/psicología , Heridas y Lesiones/psicología , Niño , Familia/psicología , Femenino , Humanos , Modelos Logísticos , Masculino , Encuestas y Cuestionarios , Heridas y Lesiones/etiología , Heridas y Lesiones/prevención & controlRESUMEN
Renal mesangial cell hypertrophy is a characteristic of diabetic nephropathy as well as a response to renal stress or injury. Because hypertrophy is a result of increased protein content per cell without DNA replication, those proteins that control the cell cycle, such as the cyclin kinase inhibitor p21, represent fertile ground for studying the mechanism of this structural alteration. A key role for p21 in promoting mesangial cell (MC) hypertrophy has been established using p21 knockout mouse models. Furthermore, some of the biologic effects of IGF-1, including cell proliferation, have been shown to be positively influenced by p21. In an attempt to begin to translate these findings ultimately to the bedside, methods to attenuate p21 levels in wild-type kidney cells were examined. With the use of a phosphorothioated antisense oligodeoxynucleotide (ODN) to p21, which has previously been shown to decrease specifically and effectively p21 protein levels in a variety of cell types, it is shown that attenuation of p21 in MC leads to a dose-dependent reduction of hypertrophy in the milieu of hyperglycemic culture media. Furthermore, the hypertrophic effect of the IGF-1 on MC is also attenuated using the same antisense p21 ODN. There was no evidence of apoptosis or other toxicity in MC transfected with the concentrations of antisense p21 ODN used in these experiments. Because the use of antisense ODN in human disease is already established in other medical disciplines, the stage is now set for the use of antisense p21 ODN to attenuate renal cell hypertrophy in vivo, leading to a new strategy for treatment of diabetic nephropathy and other diseases characterized by MC hypertrophy.
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Ciclinas/biosíntesis , Mesangio Glomerular/patología , Hiperglucemia/genética , Factor I del Crecimiento Similar a la Insulina/fisiología , Inhibidor p21 de las Quinasas Dependientes de la Ciclina , Ciclinas/efectos de los fármacos , Humanos , Hiperglucemia/patología , Hipertrofia , Oligodesoxirribonucleótidos Antisentido/farmacologíaRESUMEN
The tonic smooth muscles of lower esophageal sphincter (LES) and internal anal sphincter (IAS) are subject to modulation by the neurohumoral agents. We report that angiotensin (Ang) II-induced contraction of rat IAS and LES smooth muscle cells (SMC) was inhibited by Clostridium botulinum C3 exozyme, HA 1077 and Y 27632, suggesting a role for Rho kinase and a Rho-associated kinase (ROK). Ang II-induced contraction of the SMC was also attenuated by genistein, antibodies to the pp60(c-src), p(190) RhoGTPase-activating protein (p190 RhoGAP), carboxyl terminus of Galpha13, carboxyl terminus peptide, and ADP ribosylation factor (ARF) antibody. Ang II-induced increase in p(190) RhoGAP tyrosine phosphorylation was attenuated by genistein. Furthermore, Ang II-induced increase in smooth muscle tone and phosphorylation of myosin light chain (MLC; 20 kDa; MLC20-P) were attenuated by Y 27632 and genistein. The results suggest an important role for Galpha13 and pp60(c-src) in the intracellular events responsible for the activation of RhoA/ROK in Ang II-induced contraction of LES and IAS SMC.
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Contracción Muscular/fisiología , Miocitos del Músculo Liso/fisiología , Proteínas Serina-Treonina Quinasas/metabolismo , Transducción de Señal/fisiología , Proteínas de Unión al GTP rho/metabolismo , ADP Ribosa Transferasas , Canal Anal/fisiología , Angiotensina II/farmacología , Animales , Anticuerpos/farmacología , Toxinas Botulínicas , Inhibidores Enzimáticos/farmacología , Unión Esofagogástrica/fisiología , Péptidos y Proteínas de Señalización Intracelular , Contracción Muscular/efectos de los fármacos , Músculo Liso/efectos de los fármacos , Músculo Liso/fisiología , Miocitos del Músculo Liso/efectos de los fármacos , Miocitos del Músculo Liso/ultraestructura , Cadenas Ligeras de Miosina/efectos de los fármacos , Cadenas Ligeras de Miosina/metabolismo , Fosforilación , Ratas , Transducción de Señal/efectos de los fármacos , Vasoconstrictores/farmacología , Quinasas Asociadas a rhoRESUMEN
We examined the role of mitogen-activated protein kinase (p(44/42) MAPK) in ANG II-induced contraction of lower esophageal sphincter (LES) and internal anal sphincter (IAS) smooth muscles. Studies were performed in the isolated smooth muscles and cells (SMC). ANG II-induced changes in the levels of phosphorylation of different signal transduction and effector proteins were determined before and after selective inhibitors. ANG II-induced contraction of the rat LES and IAS SMC was inhibited by genistein, PD-98059 [a specific inhibitor of MAPK kinases (MEK 1/2)], herbimycin A (a pp60(c-src) inhibitor), and antibodies to pp60(c-src) and p(120) ras GTPase-activating protein (p(120) rasGAP). ANG II-induced contraction of the tonic smooth muscles was accompanied by an increase in tyrosine phosphorylation of p(120) rasGAP. These were attenuated by genistein but not by PD-98059. ANG II-induced increase in phosphorylations of p(44/42) MAPKs and caldesmon was attenuated by both genistein and PD-98059. We conclude that pp60(c-src) and p(44/42) MAPKs play an important role in ANG II-induced contraction of LES and IAS smooth muscles.
Asunto(s)
Angiotensina II/farmacología , Sistema Digestivo/efectos de los fármacos , Proteína Quinasa 1 Activada por Mitógenos/fisiología , Proteínas Quinasas Activadas por Mitógenos/fisiología , Contracción Muscular/fisiología , Músculo Liso/efectos de los fármacos , Proteínas Proto-Oncogénicas pp60(c-src)/fisiología , Animales , Anticuerpos/farmacología , Benzoquinonas , Proteínas de Unión a Calmodulina/metabolismo , Fenómenos Fisiológicos del Sistema Digestivo , Inhibidores Enzimáticos/farmacología , Femenino , Flavonoides/farmacología , Genisteína/farmacología , Técnicas In Vitro , Lactamas Macrocíclicas , Masculino , Proteína Quinasa 3 Activada por Mitógenos , Contracción Muscular/efectos de los fármacos , Músculo Liso/fisiología , Fosforilación , Proteínas Tirosina Quinasas/antagonistas & inhibidores , Proteínas Proto-Oncogénicas pp60(c-src)/antagonistas & inhibidores , Proteínas Proto-Oncogénicas pp60(c-src)/inmunología , Quinonas/farmacología , Ratas , Ratas Sprague-Dawley , Rifabutina/análogos & derivados , Tirosina/metabolismo , Proteína Activadora de GTPasa p120/inmunología , Proteína Activadora de GTPasa p120/farmacologíaRESUMEN
Studies were performed to compare the actions of Ang II in the internal anal sphincter (IAS) vs. lower esophageal sphincter (LES) smooth muscles in vitro, in opossum and rabbit. Studies also were carried out in isolated smooth muscle cells. In opossum, Ang II produced no discernible effects in the IAS, but did produce a concentration-dependent contraction in the LES. Conversely, in the rabbit, while Ang II caused a modest response in the LES, it caused a significant contraction in the IAS. The contractile responses of Ang II in the opossum LES were mostly resistant to different neurohumoral antagonists but were antagonized by AT1 antagonist losartan. AT2 antagonist PD 123,319, rather than inhibiting, prolonged the contractile action of Ang II. The contractile actions of Ang II in the opossum LES were not modified by the tyrosine kinase inhibitors (genistein and tyrphostin 1 x 10(-6) M) but were partially attenuated by the PKC inhibitor H-7 (1 x 10(-6) M), Ca2+ channel blocker nicardipine (1 x 10(-5) M), Rho kinase inhibitor HA-1077 (1 x 10(-7) M) or p(44/42) MAP kinase inhibitor PD 98059 (5 x 10(-5) M). The combination of HA-1077 and H-7 did not cause an additive attenuation of Ang II responses. Western blot analyses revealed the presence of both AT1 and AT2 receptors. We conclude that Ang lI-induced contraction of sphincteric smooth muscle occurs primarily by the activation of AT1 receptors at the smooth muscle cells and involves multiple pathways, influx of Ca2+, and PKC, Rho kinase and p(44/42) MAP kinase.
Asunto(s)
1-(5-Isoquinolinesulfonil)-2-Metilpiperazina/análogos & derivados , Canal Anal/efectos de los fármacos , Angiotensina II/farmacología , Esófago/efectos de los fármacos , Músculo Liso/efectos de los fármacos , 1-(5-Isoquinolinesulfonil)-2-Metilpiperazina/farmacología , Canal Anal/fisiología , Animales , Relación Dosis-Respuesta a Droga , Combinación de Medicamentos , Esófago/fisiología , Femenino , Flavonoides/farmacología , Genisteína/farmacología , Imidazoles/farmacología , Losartán/farmacología , Masculino , Contracción Muscular/efectos de los fármacos , Contracción Muscular/fisiología , Músculo Liso/fisiología , Nicardipino/farmacología , Zarigüeyas , Piridinas/farmacología , Conejos , Especificidad de la Especie , Tirfostinos/farmacologíaRESUMEN
Effect of ANG II was investigated in in vitro smooth muscle strips and in isolated smooth muscle cells (SMC). Among different species, rat internal and sphincter (IAS) smooth muscle showed significant and reproducible contraction that remained unmodified by different neurohumoral inhibitors. The AT(1) antagonist losartan but not AT(2) antagonist PD-123319 antagonized ANG II-induced contraction of the IAS smooth muscle and SMC. ANG II-induced contraction of rat IAS smooth muscle and SMC was attenuated by tyrosine kinase inhibitors genistein and tyrphostin, protein kinase C (PKC) inhibitor H-7, Ca(2+) channel blocker nicardipine, Rho kinase inhibitor Y-27632 or p(44/42) mitogen-activating protein kinase (MAPK(44/42)) inhibitor PD-98059. Combinations of nicardipine and H-7, Y-27632, and PD-98059 caused further attenuation of the ANG II effects. Western blot analyses revealed the presence of both AT(1) and AT(2) receptors. We conclude that ANG II causes contraction of rat IAS smooth muscle by the activation of AT(1) receptors at the SMC and involves multiple intracellular pathways, influx of Ca(2+), and activation of PKC, Rho kinase, and MAPK(44/42).