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Knowledge regarding the occurrence of short-chain and medium-chain chlorinated paraffins (SCCPs and MCCPs) in foodstuffs and their dietary exposure risks for rural Tibetan residents remains largely unknown. Herein, we collected main foodstuffs (including highland barley, vegetables, Tibetan butter, mutton, and yak beef) across the rural Tibetan Plateau and characterized the CP profiles and concentrations. The highest SCCPs concentrations were detected in Tibetan butter (geometric mean (GM): 240.6 ng/g wet weight (ww)), followed by vegetables (59.4 ng/g ww), mutton (51.4 ng/g ww), highland barley (46.3 ng/g ww), and yak beef (31.7 ng/g ww). For MCCPs, the highest concentrations were also detected in Tibetan butter (319.5 ng/g ww), followed by mutton (181.9 ng/g ww), vegetables (127.0 ng/g ww), yak beef (71.2 ng/g ww), and highland barley (30.3 ng/g ww). The predominant congener profiles of SCCPs were C13Cl7-8 in mutton and yak beef, C10Cl7-8 in Tibetan butter, and C10-11Cl6-7 in highland barley and vegetables. The predominant congener profiles of MCCPs were C14Cl7-9 in all sample types. Combined with our previous results of free-range chicken eggs, the median estimated daily intakes (EDIs) of SCCPs and MCCPs via diet for Tibetan rural adults and children was estimated to be 728.8 and 1853.9 ng/kg bw/day and 2565.6 and 5952.8 ng/kg bw/day, respectively. In the worst scenario, MCCPs might induce potential health risks for rural Tibetan population. To our knowledge, this is the first systematic dietary exposure research of SCCPs and MCCPs in the remote rural areas.
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Exposición Dietética , Parafina , Población Rural , Tibet , Humanos , Exposición Dietética/estadística & datos numéricos , Exposición Dietética/análisis , Parafina/análisis , Población Rural/estadística & datos numéricos , Adulto , Contaminación de Alimentos/análisis , Contaminación de Alimentos/estadística & datos numéricos , Niño , Persona de Mediana Edad , Hidrocarburos Clorados/análisis , Medición de Riesgo , Femenino , Masculino , China , Preescolar , Adolescente , Adulto Joven , Dieta/estadística & datos numéricos , Contaminantes Ambientales/análisisAsunto(s)
Enfermedades Cardiovasculares , Hipertensión , Adulto , Humanos , Pueblos del Este de Asia , Prevalencia , Factores de Riesgo , EtnicidadRESUMEN
BACKGROUND: To compare the demographic and clinical features, laboratory and imaging findings in mycoplasma pneumoniae pneumonia (MPP) children with non-MPP (NMPP) children and general MPP (GMPP) children with refractory MPP (RMPP) children and analysis the relationship with the severity of disease. METHODS: The study included 265 children with MPP and 230 children with NMPP in the Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University from 2020 to 2021. The children with MPP included RMPP (n = 85) and GMPP (n = 180). Demographic and clinical characteristics, laboratory and imaging findings of all children were measured as baseline data within 24 h after admission and the differences between MPP and NMPP, RMPP and GMPP patients were compared. ROC curves were used to evaluate the diagnostic and predictive value of different indicators for RMPP. RESULTS: Fever duration and hospital stay in children with MPP were longer than those with NMPP. The number of patients with imaging features of pleural effusion, lung consolidation and bronchopneumonia in MPP group was significantly higher than that in NMPP group. Compared with NMPP group, the levels of C-reactive protein (CRP), procalcitonin (PCT), serum amyloid A (SAA), erythrocyte sedimentation rate (ESR), lactic dehydrogenase (LDH), prothrombin time (PT), fibrinogen (FIB) and D-dimer and inflammatory cytokines (interleukin [IL]-6, IL-8, IL-10 and IL-1ß) in MPP group were significantly higher (P < 0.05). The clinical symptoms and pulmonary imaging findings were more severe in RMPP group. The levels of white blood cell (WBC), CRP, PCT, SAA, ESR, alanine aminotransferase (ALT), LDH, ferritin, PT, FIB, D-dimer and inflammatory cytokines in RMPP group were higher than those in GMPP group. There was no significant difference in the level of lymphocyte subsets between the RMPP and GMPP group. IL-6, IL-10, LDH, PT, D-dimer and lung consolidation were independent risk factors for RMPP. IL-6 levels and LDH activity were good predictors of RMPP. CONCLUSION: In conclusion, there were differences in clinical characteristics and serum inflammatory markers between MPP group and NMPP group, RMPP group and GMPP group. IL-6, IL-10, LDH, PT and D-dimer can be used as predictive indicators for RMPP.
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Neumonía por Mycoplasma , Humanos , Niño , Neumonía por Mycoplasma/diagnóstico , Interleucina-10 , Interleucina-6 , Estudios Retrospectivos , Biomarcadores , Mycoplasma pneumoniae , Proteína C-Reactiva/análisis , Citocinas , Polipéptido alfa Relacionado con CalcitoninaRESUMEN
Aquaculture of the blood clam Tegillarca granosa accounts for approximately 50% of Arcidae (ark shell) production in China. Vibrio infection severely threatens the sustainability of the clam aquaculture industry. Exposure to Vibrio induces an immune response in blood clams. However, the underlying mechanism remains poorly understood. In this study, immune responses of hemocytes in blood clams were detected after Vibrio infection; the immersion method was used in vivo to mimic the clam's natural infection process. After 24 h of exposure to Vibrio infection, the Vibrio load in hemolymph fluid in both the treatment â (25,033.33 ± 19,563.11 CFU/mL) and treatment â ¡ (122,163.33 ± 194,409.49 CFU/mL) groups were significantly higher, than that in the control group (13.67 ± 37.73 CFU/mL) (P < 0.05). Correspondingly, the production of intracellular reactive oxygen species was approximately 1.40 (treatment â ) and 2.12 (treatment â ¡) fold higher than that in the control group (P < 0.05), and the induced DNA damage showed a similar trend (P < 0.05). Vibrio infection also significantly increased lysozyme content, adenosine triphosphate content, and peroxidase isozyme activity, in both the serum and hemocyte lysates (P < 0.05). The expression of immune-associated genes (ABCA3, c-Myc, Caspase 3, and HSP70) was upregulated under infection conditions. The phagocytic activity was approximately 1.99 (treatment â ) and 2.57 (treatment â ¡) fold that in control clams (P < 0.05). In addition, the total hemocyte count and red granulocyte percentage both significantly decreased by approximately 75-90% after Vibrio infection. These results provided novel insights into the mechanism of hemocyte immunity in T. granosa against Vibrio infection, which may aid in the future prevention and control of Vibrio infection in vivo.
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Arcidae , Bivalvos , Vibriosis , Vibrio , Animales , Hemocitos , Vibrio/fisiología , Vibriosis/veterinaria , InmunidadRESUMEN
This study elucidates the association between urinary zinc concentration and the risk of developing dyslipidemia and its subtypes in China's ethnic minority residents. Based on the baseline survey data of the Chinese Multi-Ethnic Cohort (CMEC) study, 10,620 subjects were included in the study. Logistic regression analysis evaluated the relationship between urinary zinc concentration and dyslipidemia and its subtypes. After adjustment, compared with urinary zinc concentration quartile 1 (Q1), the odds ratios (ORs) and 95% confidence intervals (95% CIs) of dyslipidemia participants in the quartile 2 (Q2), quartile 3 (Q3), and quartile 4 (Q4) groups were 1.091 (0.963, 1.237), 1.151 (1.051, 1.304), and 1.393 (1.230, 1.579), respectively (P for trend < 0.001). While that of hypertriglyceridemia participants in the Q2, Q3, and Q4 groups were 1.130 (0.979, 1.306), 1.283 (1.113, 1.480), and 1.483 (1.287, 1.709), respectively (P for trend < 0.001). Lastly, the ORs and 95% CIs of hyperbetalipoproteinemia participants in the Q2, Q3, and Q4 groups were 1.166 (0.945, 1.439), 1.238 (1.007, 1.522), and 1.381 (1.126, 1.695), respectively (P for trend < 0.002). This study found that urinary zinc concentrations were not associated with hypercholesterolemia and hypoalphalipoproteinemia. The dose-response relationship was non-linear between urinary zinc concentration and dyslipidemia, hypertriglyceridemia and hyperbetalipoproteinemia (P for trend < 0.001). In the stratified analysis, urinary zinc levels were positively associated with the risk of dyslipidemia, hypertriglyceridemia, and hyperbetalipoproteinemia in male, ≥ 60 years old, Miao nationality, hypertension, diabetes, and BMI ≥ 24.0 kg/m2 subgroups. Our study provides some possible evidence that elevated urinary zinc concentrations are associated with an increased risk of dyslipidemia, hypertriglyceridemia, hyperbetalipoproteinemia.
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Dislipidemias , Hiperlipoproteinemia Tipo II , Hipertrigliceridemia , Humanos , Masculino , Persona de Mediana Edad , Zinc , Etnicidad , Pueblos del Este de Asia , Grupos Minoritarios , Dislipidemias/epidemiologíaRESUMEN
Metals play an important role in the development of diabetes mellitus (DM). The association of metals with diabetes among the Dong ethnicity in China remains poorly understood. The current study aimed to evaluate the association of single metal exposure and multi-metal co-exposure with DM risk. Urinary concentrations of arsenic, cadmium, chromium, copper, iron, lead, manganese, mercury, molybdenum, nickel, strontium, vanadium, and zinc were measured using inductively coupled plasma-mass spectrometry (ICP-MS) among 4479 Dong ethnic participants aged 30-79 years from the China Multi-Ethnic Cohort (CMEC) study. Based on tertiles, the metal exposure can be divided into three groups: low, middle, and high exposure. Multivariate logistic regression models and principal component analysis were performed to determine exposure to single-metal and multi-metal co-exposure in relation to DM. A decrease in risk of DM was associated with iron (OR = 0.78, 95% CI: 0.61-1.00 and 0.68, 0.53-0.88 for the middle and high vs. low) and strontium (OR = 0.87, 95% CI: 0.69-1.12 and 0.67, 0.51-0.86 for the middle and high vs. low), respectively. A principal component 3 (PC3) characterized by iron and strontium showed an inverse association with DM. A principal component 4 (PC4) characterized by manganese and lead positively associated with DM. Exposure to high concentrations of urinary iron and strontium may reduce the risk of diabetes mellitus. This study revealed an increase in the risk of diabetes mellitus by co-exposure to high concentrations of urinary manganese and lead.
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Arsénico , Diabetes Mellitus , Humanos , Estudios de Cohortes , Manganeso/toxicidad , Etnicidad , Hierro , Estroncio , Diabetes Mellitus/epidemiología , Arsénico/toxicidad , Vanadio , China/epidemiologíaRESUMEN
BACKGROUND: Although it is known that obesity is inseparable from diabetes, many anthropometric indices are used for determining obesity. At the same time, research on the predictive indices of diabetes in Chinese minority populations is lacking. Therefore, this study determines the relationship between different anthropometric indices and diabetes, and identifies the best index and best cut-off values for predicting diabetes. METHOD: In total, 11,035 Dong and Miao ethnic participants (age: 30-79 years) from the China Multi-Ethnic Cohort study were included. The logistic regression model was used to examine the relationship between the different anthropometric indices and diabetes risk. The receiver operating characteristic curve and the area under the curve (AUC) were used to identify the best predictor of diabetes. RESULTS: In multivariate adjusted logistic regression models, body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), a body shape index (ABSI), body roundness index (BRI), and visceral adiposity index (VAI) were positively correlated with diabetes risk. Among Chinese Dong men and women and Miao men, WHR had the largest AUC (0.654/0.719/0.651). Among Miao women, VAI had the largest AUC(0.701). The best cut-off values of WHR for Dong men and women and Miao men were 0.94, 0.92, and 0.91, respectively. The best cut-off value of VAI for Miao women was 2.20. CONCLUSION: Obesity indicators better predict diabetes in women than men. WHR may be the best predictor of diabetes risk in both sex of Dong ethnicity and Miao men, and VAI may be the best predictor of diabetes risk in Miao women.
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Diabetes Mellitus , Etnicidad , Adulto , Anciano , Índice de Masa Corporal , China/epidemiología , Estudios de Cohortes , Estudios Transversales , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Obesidad/complicaciones , Obesidad Abdominal , Valor Predictivo de las Pruebas , Curva ROC , Factores de Riesgo , Circunferencia de la Cintura , Relación Cintura-Estatura , Relación Cintura-CaderaRESUMEN
It has been previously reported that family history of hypertension (FHH) and exposure to metals are each independent risk factor for hypertension, but the interaction between the two in relation to hypertension risk has been poorly studied. The object of this study is Dong ethnic group in Guizhou, China. The impacts of exposure to metals and FHH on hypertension incidence were examined by using the restrictive cubic spline (RCS) model as well as the multivariate logistic regression model. As a result, FHH, together with cobalt and lead exposure, was identified to show independent significant correlation with hypertension incidence (P < 0.05). The risk of hypertension increased with the increase in lead and cobalt exposure quartiles. Typically, the RCS model revealed such dose-response relation. To further confirm the association of cobalt, lead, and FHH with the risk of hypertension, multiplication and addition models were used to analyze the influence of the interactions between these variables on the risk of hypertension. The results showed that there was a multiplying interaction between the influence of the FHH and cobalt on the risk of hypertension. As for the additive interaction between cobalt and FHH, the relative excess risk due to interaction (RERI) was determined to be 0.596 (95% Cl: 0.001-1.191), the attributable proportion due to interaction (AP) was calculated as 0.256 (95% Cl: 0.075-0.437), whereas the synergy index (S) was identified to be 1.814 (95% Cl: 1.080-3.047). Our study provides some limited evidence that a FHH and cobalt exposure synergistically promote the prevalence of hypertension.
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Cobalto , Hipertensión , Cobalto/toxicidad , Estudios Transversales , Humanos , Hipertensión/inducido químicamente , Hipertensión/epidemiología , Prevalencia , Factores de RiesgoRESUMEN
Exposure to heavy metals in the environment exerts serious effects on kidney health. However, the effects of joint exposure on the kidneys have been rarely studied, particularly in non-occupational exposure high-risk populations. This study provided a reference threshold range of heavy metals in urine and explored the effect of joint exposure on nephrolithiasis in men. The data were obtained from the China Multi-Ethnic Cohort database, and 1502 men were included in the study. A two-piece-wise regression model was used to assess the dose-response relationship between heavy metal exposure and nephrolithiasis. The least absolute shrinkage and selection operator regression model was used to calculate the score of joint exposure to heavy metals. The threshold effect analysis revealed a linear relationship between the concentration of arsenic (As) in the urine and the prevalence of nephrolithiasis, whereas a nonlinear relationship was observed with cadmium (Cd), chromium (Cr), mercury (Hg), and lead (Pb). In addition, As, Cd, Cr, Hg, and Pb may significantly affect the joint exposure effect. Moreover, the final risk of nephrolithiasis increased by 123% (P for trend < 0.001). This study found a threshold relationship between heavy metals (Cd, Cr, Hg, Pb) in male urine and the occurrence of nephrolithiasis. Joint exposure to heavy metals in urine caused a high-risk effect on nephrolithiasis. The study provided a reference threshold value of related studies and indicated that environmental pollution caused by heavy metals should be reduced.
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Arsénico , Mercurio , Metales Pesados , Nefrolitiasis , Arsénico/análisis , China/epidemiología , Monitoreo del Ambiente , Humanos , Masculino , Mercurio/toxicidad , Metales Pesados/análisis , Metales Pesados/toxicidad , Nefrolitiasis/inducido químicamente , Nefrolitiasis/epidemiología , Prevalencia , Medición de RiesgoRESUMEN
Electrochemical precipitation is a promising technique for hardness abatement without the addition of external ions. However, the scale layer on cathode deteriorated the removal efficiency and limited the practical application. Herein, a fenced cathode structure was designed to prevent cathodic precipitation. The cathode was fenced by a crystallization-inducing material for separating the OH- production and crystallization processes. Precipitation on the cathode was confirmed to shift to the crystallization-inducing material, and the clean fenced cathode provided efficient long-term OH- production. At a current density of 40 A/m2, the Ca2+ or Mg2+ removal efficiency increased by 12.8% or 46.1%, respectively, compared to those of a traditional cathode. Thermodynamic equilibrium in synthetic water and mine water, mass transfer and the location of precipitation were analyzed to elucidate the electrochemical precipitation process. The enhanced mechanism was ascribed to the crystallization-inducing material, which remarkably promoted the crystallization process, and hindered OH- migration, thereby increased the pH of alkaline microenvironment. Notably, a recovery design was proposed to recover pure calcite and brucite from alkalinity-free wastewater. The design reveals a promising strategy for enhancing the crystallization process and reducing cathodic scale, also initiating a new research direction toward hardness removal.
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BACKGROUND: Airway remodeling is one of the most important pathological features of chronic asthma. This study aimed to determine whether microRNA-221 (hereafter, miR-221) can affect airway remodeling in a mouse model of ovalbumin (OVA)-induced chronic asthma. METHODS: Adeno-associated viruses (AAVs) "Bearing miR-221 sponges" were used to downregulate miR-221 in asthmatic mice. Staining with hematoxylin and eosin (H&E), Masson trichrome, and periodic acid-Schiff reagent was used to assess histological changes. The affected signaling pathway in mouse airway smooth muscle cells (ASMCs) was also identified by gene chip technology. A PI3K/AKT-inhibitor (LY294002) was used to confirm the role of the pathway in ASMCs. RESULTS: The inhibition of miR-221 in a murine asthma model was found to reduce airway hyper-responsiveness, mucus metaplasia, airway inflammation, and airway remodeling (p < 0.05). Furthermore, miR-221 was found to regulate collagen deposition in the extracellular matrix (ECM) of ASMCs. Bioinformatics analysis and western blot analysis confirmed that the PI3K-AKT pathway was involved in ECM deposition in ASMCs. CONCLUSION: miR-221 might play a crucial role in the mechanism of remodeling via the PI3K/AKT pathway in chronic asthma and it could be considered as a potential target for developing therapeutic strategies.
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The present study aimed to examine the functional role of miR-223 in the regulation of mast cell apoptosis. Overexpressed miR-223 in mast cells transfected by Lipofectamine 2000 was used as a model, and miR-223 was found to promote mast cell apoptosis. To investigate the underlying mechanisms involved, the potential and putative target molecules of miR-223 were detected by bioinformatical analysis using predictive software, and western blotting. Insulin-like growth factor-1 receptor (IGF-1R) was found to be the functional target of miR-223 in the promotion of cell apoptosis. The downstream PI3K/protein kinase B (Akt) signaling pathway was also inhibited, and signaling was mediated by IGF-1R. Furthermore, the relative luciferase activity of the reporter containing the 3'-untranslated region (3'-UTR) of IGF-1R was significantly suppressed, while suppression of miR-223-inhibited IGF-1R protein expression was also observed. In conclusion, the results suggest that IGF-1R is the functional target for miR-223 promotion of cell apoptosis, and its downstream PI3K/Akt signaling pathway was suppressed by miR-223 through targeting of IGF-1R.
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In this study, we aimed to assess the effects of microRNA-223 (miR-223) on interleukin-6 (IL-6) secretion in mast cells and determine the underlying molecular mechanisms. Mast cells (P815) were transfected with miR-223 lentiviral vector and miR-223 inhibitor. miR-223 expression was then evaluated using reverse transcription-quantitative PCR (RT-qPCR). IL-6 levels in the supernatant were analyzed using enzyme-linked immunosorbent assay. The signaling pathways in mast cells with downregulated miR-223 were initially evaluated by gene chip. Downregulation of miR-223 and its target gene was tested using a luciferase reporter assay. The expression of phosphate-AKT (p-AKT) and its target protein insulin-like growth factor-1 receptor (IGF1R) was assessed by western blot analysis. Phosphatidylinositol 3-kinase (PI3K)-inhibitor (LY294002) and insulin-like growth factor-1 (IGF1) were used to determine the effect of miR-223 on IL-6 secretion in mast cells. The results showed that microRNA-223 reduced IL-6 concentration in the mast cells. The gene chip results predicted an induction of the PI3K-AKT signaling pathway in the mast cells. Luciferase reporter assay confirmed IGF1R gene to be a target of miR-223. The p-AKT and IGF1R levels increased following miR-223 downregulation in mast cells. In addition, the specific PI3Kinhibitor LY294002 decreased IL-6 secretion. Incubation with IGF1 resulted in the induction of IL-6 secretion in miR-223expressing mast cells. In conclusion, it was shown that miR-223 reduces IL-6 secretion in mast cells by inhibiting the IGF1R/PI3K signaling pathway.
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Interleucina-6/metabolismo , Mastocitos/metabolismo , MicroARNs/metabolismo , Fosfatidilinositol 3-Quinasa/metabolismo , Receptor IGF Tipo 1/metabolismo , Transducción de Señal , Animales , Western Blotting , Cromonas/farmacología , Perfilación de la Expresión Génica , Regulación de la Expresión Génica/efectos de los fármacos , Genes Reporteros , Luciferasas/metabolismo , Mastocitos/efectos de los fármacos , Ratones , Morfolinas/farmacología , Inhibidores de Proteínas Quinasas/farmacología , Transducción de Señal/efectos de los fármacosRESUMEN
Mast cells play a pivotal role in the immediate reaction in asthma. In a previous study, it was found that MicroRNA-221 (miR-221) was associated with asthma. Hence, in the present study, the role and the potential mechanisms of miR-221 on immunoglobulin E (IgE)-mediated activation of mast cells degranulation were investigated. MiR-221 expression was first quantified by qRT-PCR in IgE-mediated activation of mast cells. RBL-2H3 cells were then transfected with miR-221 mimic or miR-221 inhibitor, the IgE-mediated degranulation was detected in mast cells. The influence of miR-221 on expression of phospholipase C gamma (PLCγ1), p-PLCγ1, protein kinase B (Akt), phospho-Akt (p-Akt), inhibitor of kappa B (IκB-α), and phospho-IκB-α (p-IκB-α) were examined by Western blot, whereas free calcium ion (Ca(2+)) level was measured by flow cytometry and NF-κB expression was determined by EMSA. Phosphoinositide 3-kinase (PI3K)-inhibitor (LY294002) and NF-κB-inhibitor [pyrrolidine dithiocarbamate (PDTC)] were used to investigate the role of PI3K/Akt pathway and NF-κB in miR-221 promoting IgE-mediated activation of mast cells degranulation. The expression of miR-221 was upregulated in IgE-mediated activation of mast cells, and it was overexpressed in miR-221 mimic transfected cells. The degranulation was found to be significantly increased in miR-221 overexpressed cells while it was found to be significantly decreased in miR-221 downregulated cells. The expression of p-PLCγ1, p-Akt, p-IκB-α as well as NF-κB and Ca(2+) release were increased in miR-221 overexpressed cells. PI3K-inhibitor (LY294002) could rescue the promotion of degranulation caused by miR-221 in IgE-mediated activation of mast cells. However, NF-κB-inhibitor (PDTC) could not rescue the promotion of degranulation caused by miR-221 in IgE-mediated activation of mast cells. MiR-221 promotes IgE-mediated activation of mast cells degranulation by PI3K/Akt/PLCγ/Ca(2+) signaling pathway, in a non-NF-κB dependent manner.
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Degranulación de la Célula/efectos de los fármacos , MicroARNs/inmunología , Fosfatidilinositol 3-Quinasas/metabolismo , Transducción de Señal , Animales , Calcio/metabolismo , Línea Celular , Humanos , Inmunoglobulina E/inmunología , Mastocitos , MicroARNs/antagonistas & inhibidores , MicroARNs/genética , FN-kappa B/metabolismo , Fosfolipasa C gamma/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas , Ratas Wistar , Transducción de Señal/efectos de los fármacos , TransfecciónRESUMEN
Mast cells play a central role in asthma. Moreover, serum miRNA-221-3p (miR-221) has been shown to be markedly increased in children with asthma. In the current study, we aimed to examine miR-221 expression in an asthma model and elucidate the mechanisms regulating interleukin (IL)-4 secretion in mast cells. Using polymerase chain reaction, we found that miR-221 was upregulated in a murine asthma model and in P815 mast cells after lipopolysaccharide (LPS) stimulation. Moreover, miR-221 upregulated IL-4 secretion from P815 cells, as shown by enzyme-linked immunosorbent assays. Bioinformatics analysis, luciferase reporter gene assays, and western blotting showed that phosphatase and tensin homolog (PTEN) was a target of miR-221 and could block IL-4 secretion stimulated by miR-221. The phosphorylation of p38 (protein) and activity of nuclear factor-kappaB (NF-κB) were increased after overexpression of miR-221, as shown by electrophoretic mobility shift assays. Finally, treatment with specific inhibitors could block IL-4 secretion. In conclusion, miR-221, which was overexpressed in a murine asthma model, stimulated IL-4 secretion in mast cells through a pathway involving PTEN, p38, and NF-κB.
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Interleucina-4/metabolismo , Mastocitos/metabolismo , MicroARNs/genética , Proteínas de Microfilamentos/metabolismo , FN-kappa B/metabolismo , Monoéster Fosfórico Hidrolasas/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Animales , Asma/genética , Asma/inmunología , Asma/metabolismo , Línea Celular , Citocinas/metabolismo , Modelos Animales de Enfermedad , Femenino , Regulación de la Expresión Génica , Lipopolisacáridos/inmunología , Mastocitos/inmunología , Fosfohidrolasa PTEN/genética , Fosforilación , Inhibidores de Proteínas Quinasas/farmacología , Interferencia de ARN , Tensinas , Receptores Toll-Like/genética , Receptores Toll-Like/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/antagonistas & inhibidoresRESUMEN
OBJECTIVE: To evaluate the value of clinical signs in the identification of Mycoplasma pneumonia in children's community acquired pneumonia. METHOD: We searched the Cochrane library, PubMed, CNKI, Wan Fang and VIP databases. According to the inclusion and exclusion criterias, we selected and extracted the related information in the literature. According to the QUADAS evaluation system, we established the quality evaluation standard to evaluate the quality of the included studies and analyzed the difference of the clinical manifestations between Mycoplasmae pneumoniae and non-Mycoplasma pneumoniae in children's community acquired pneumonia. We used the RevMan 5.3 software to do the meta-analysis and collected the data according to the requirements. We calculated the pooled sensitivities, specificities and 95%CIs. Then we calculated the negative and positive likelihood ratio, the ratio of the diagnosis and the pre-/post-test probabilities with 95% CIs. RESULT: A total of 11 articles were included in the literature. In summary, the cases of the clinical signs of true positive (TP) and false positive (FP) were as follows : chest pain: TP: 287, FP: 1090; rales: TP: 1906, FP: 6886; headache: TP: 590, FP: 2051; pleural effusion: TP: 10, FP: 16; consolidation: TP: 75, FP: 83; emphysema: TP: 443, FP: 116. The pooled sensitivity, the pooled specificity, the diagnostic ratio (DOR) and 95% CI were: chest pain: pooled sensitivity: 0.12, 95% CI: 0.10-0.13, pooled specificity: 0.89, 95% CI: 0.88-0.90, DOR: 1.05, 95% CI: 0.92-1.21; rales: pooled sensitivity: 0.66, 95% CI: 0.64, 0.67, pooled specificity: 0.36, 95% CI: 0.35, 0.37, DOR: 1.12, 95% CI: 1.02, 1.22; headache: pooled sensitivity: 0.23, 95% CI: 0.21-0.25, pooled specificity: 0.80, 95%CI: 0.79-0.80, DOR: 1.16, 95%CI: 1.05-1.29; pleural effusion: pooled sensitivity: 0.04, 95% CI: 0.02, 0.08, pooled specificity: 0.98, 95% CI: 0.96, 0.99, DOR: 1.28, 95% CI: 0.56, 2.89; consolidation: pooled sensitivity: 0.32, 95% CI: 0.26, 0.39, pooled specificity: 0.87, 95% CI: 0.84, 0.90, DOR: 1.88, 95% CI: 1.23, 2.90; emphysema: pooled sensitivity: 0.22, 95% CI: 0.17, 0.29, pooled specificity: 0.73, 95% CI: 0.69, 0.77, DOR: 1.05, 95% CI: 0.68, 1.61. CONCLUSION: The value of clinical symptoms and signs in the identification of mycoplasma pneumonia in children's community acquired pneumonia was not significant. Although the clinical symptoms/signs of chest pain, headache, rales and chest X-ray manifestations of pleural effusion, consolidation, emphysema could suggest Mycoplasma pneumoniae infection, the presence or absence of any clinical signs were not positive or negative indicators for the identification of Mycoplasma pneumoniae infections.
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Infecciones Comunitarias Adquiridas/diagnóstico , Neumonía por Mycoplasma/diagnóstico , Dolor en el Pecho , Niño , Cefalea , Humanos , Mycoplasma pneumoniae , Derrame Pleural , Radiografía Torácica , Ruidos Respiratorios , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: Mast cells play a central role in allergic and inflammatory disorders by inducing degranulation and inflammatory mediator release. Recent reports have shown that miRNAs play an important role in inflammatory response regulation. Therefore, the role of miR-223 in mast cells was investigated. METHODS: The expression of miR-223 was quantified by quantitative real-time polymerase chain reaction (qRT-PCR) in immunoglobulin E (IgE)-mediated mast cells. After successful miR-223 inhibition by transfection, degranulation was detected in IgE-mediated mast cells. The phosphorylation of IκB-α and Akt were examined using western blotting. NF-κB was tested using electrophoretic mobility shift assay. PI3K-inhibitor (LY294002) was used to investigate whether the PI3K/Akt pathway was essential for mast cell activation. The TargetScan database and a luciferase reporter system were used to identify whether insulin-like growth factor 1 receptor (IGF-1R) is a direct target of miR-223. RESULTS: MiR-223 expression was up-regulated in IgE-mediated mast cells, whereas its down-regulation promoted mast cell degranulation. Levels of IκB-α and Akt phosphorylation as well as NF-κB were increased in miR-223 inhibitor cells. LY294002 could block the PI3K/Akt signaling pathway and rescue the promotion caused by suppressing miR-223 in mast cells. IGF-1R was identified as a direct target of miR-223. CONCLUSIONS: These findings suggest that down-regulation of miR-223 promotes degranulation via the PI3K/Akt pathway by targeting IGF-1R in mast cells.