RESUMO
Laboratory analysis of trace metals using inductively coupled plasma (ICP) spectroscopy is not cost effective, and the complex spatial distribution of soil trace metals makes their spatial analysis and prediction problematic. Thus, for the health risk assessment of exposure to trace metals in soils, portable X-ray fluorescence (PXRF) spectroscopy was used to replace ICP spectroscopy for metal analysis, and robust geostatistical methods were used to identify spatial outliers in trace metal concentrations and to map trace metal distributions. A case study was carried out around an industrial area in Nanjing, China. The results showed that PXRF spectroscopy provided results for trace metal (Cu, Ni, Pb and Zn) levels comparable to ICP spectroscopy. The results of the health risk assessment showed that Ni posed a higher non-carcinogenic risk than Cu, Pb and Zn, indicating a higher priority of concern than the other elements. Sampling locations associated with adverse health effects were identified as 'hotspots', and high-risk areas were delineated from risk maps. These 'hotspots' and high-risk areas were in close proximity to and downwind from petrochemical plants, indicating the dominant role of industrial activities as the major sources of trace metals in soils. The approach used in this study could be adopted as a cost-effective methodology for screening 'hotspots' and priority areas of concern for cost-efficient health risk management.
Assuntos
Monitoramento Ambiental/métodos , Metais Pesados/análise , Poluentes do Solo/análise , Solo/química , Oligoelementos/análise , China , Análise Custo-Benefício , Monitoramento Ambiental/estatística & dados numéricos , Humanos , Indústrias , Medição de Risco/métodos , Medição de Risco/estatística & dados numéricos , Análise Espacial , Espectrometria por Raios XRESUMO
The present research was designed to study expression of AQP2, AQP4 and AQP8 in mouse intestines induced by unprocessed and processed Euphorbia lathyris. KM mice were given by different dose lavage of unprocessed and processed Euphorbia lathyris, Euphorbia factor L1, Euphorbia factor L2, Euphorbia factor L3. Samples of mouse intestine were collected for protein levels of AQP2, AQP 4 and AQP 8 which were assessed by immunohistochemical staining and mRNA expression of AQP2, AQP 4 and AQP 8 which were quantified by Real Time-PCR. Comparing to the normal control group, the protein levels of AQP2, AQP 4 and AQP 8 were significantly decreased (P<0.05)by Semen Euphorbiae group and Semen Euphorbiae Pulveratum group (unprocessed and processed Euphorbia lathyris) induced. Protein expression of AQP2, AQP 4 and AQP 8 in the Euphorbia factor L1, Euphorbia factor L2 and Euphorbia factor L3 group were not significantly lower than normal control group. There had no differences on the levels of AQP2 and AQP 8 mRNA expressions between the high-dose group of semen Euphorbiae group, semen Euphorbiae Pulveratum group and positive control group, while significantly lower than normal control group (P<0.05). Expression of AQP4 mRNA in the Semen Euphorbiae group and Semen Euphorbiae Pulveratum group has not significantly decreased. But levels of AQP2, AQP 4 and AQP 8 mRNA in the Euphorbia factor L1 group had no significant differences in normal control group and positive control group. These findings suggest that semen Euphorbiae could regulate expression of AQP2, AQP 4 and AQP 8 protein and mRNA, which may be the possible one reason of semen Euphorbiae induces diarrhea. The semen Euphorbiae group has more significant effects on the levels of AQP2, AQP 4 and AQP 8 protein and mRNA than semen Euphorbiae Pulveratum group, which may be one of the mechanisms of processing attenuation.
Assuntos
Aquaporina 2/biossíntese , Aquaporina 4/biossíntese , Aquaporinas/biossíntese , Medicamentos de Ervas Chinesas/toxicidade , Euphorbia/química , Mucosa Intestinal/efeitos dos fármacos , Animais , Medicamentos de Ervas Chinesas/isolamento & purificação , Imuno-Histoquímica , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Camundongos EndogâmicosRESUMO
OBJECTIVE: Meta-analysis was used to assess the clinical efficacy of acupuncture treatment for simple obesity and to provide evidence-based medical data for treating obesity with acupuncture. METHODS: A comprehensive search of studies on MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials and Chinese databases (Wan Fang,CNKI and VIP) from 1 January 1915 through 30 November 2015 (MEDLINE search updated through 31 December 2015) was performed. We included only randomised controlled trials (RCTs) that used acupuncture and sham acupuncture to treat simple obesity. The effect of acupuncture on simple obesity was measured using body mass index (BMI), body fat mass (BFM), waist circumference (WC), hip circumference (HC), and body weight (BW). The Jadad scale was used to assess methodological quality. The random effects model was used in the pooled analysis to adjust for the heterogeneity of the included studies, and funnel plots were used to examine publication bias. The differences between treatment groups were reported as mean differences (MD). RESULTS: Eleven RCTs were selected after all relevant literature from the electronic databases had been screened. There were 338 and 305 participants in the acupuncture and sham acupuncture groups, respectively. Auricular and electro acupuncture were both able to reduce BMI in obese patients (MD 0.47 kg/m2, 95% CI 0.35 to 0.58, p<0.001; MD 0.50 kg/m2, 95% CI 0.38 to 0.62, p<0.001). BFM change after acupuncture treatment compared with sham treatment was statistically significant (MD 0.66 kg, 95% CI 0.51 to 0.80, p<0.001). There were also significant differences in WC and HC between the acupuncture and sham acupuncture groups (MDwc2.02 cm, 95% CI 0.21 to 3.83, p=0.03; MDHC2.74 cm, 95% CI 1.21 to 4.27, p=0.0004). BW was not statistically significantly different between the acupuncture and sham acupuncture groups (MD 0.60 kg, 95% CI -0.20 to 1.39, p=0.14). Begg's test and funnel plots showed that the potential publication bias of the included studies was very slight (p>0.05). CONCLUSION: Acupuncture for simple obesity appeared to be an effective treatment, but more studies on the safety of acupuncture used to treat simple obesity are required.
Assuntos
Terapia por Acupuntura , Obesidade/terapia , Adulto , Medicina Baseada em Evidências , HumanosRESUMO
Objective To construct a model of Seasonal Autoregressive Integrated Moving Average (SARIMA) for forecasting the epidemic of Japanese encephalitis (JE) in Xianyang, Shaanxi, China, and provide valuable reference information for JE control and prevention. Methods Theoretically epidemiologic study was employed in the research process. Monthly incidence data on JE for the period from Jan 2005 to Sep 2014 were obtained from a passive surveillance system at the Center for Diseases Prevention and Control in Xianyang, Shaanxi province. An optimal SARIMA model was developed for JE incidence from 2005 to 2013 with the Box and Jenkins approach. This SARIMA model could predict JE incidence for the year 2014 and 2015. Results SARIMA (1, 1, 1) (2, 1, 1)12 was considered to be the best model with the lowest Bayesian information criterion, Akaike information criterion, Mean Absolute Error values, the highest R2, and a lower Mean Absolute Percent Error. SARIMA (1, 1, 1) (2, 1, 1)12 was stationary and accurate for predicting JE incidence in Xianyang. The predicted incidence, around 0.3/100 000 from June to August in 2014 with low errors, was higher compared with the actual incidence. Therefore, SARIMA (1, 1, 1) (2, 1, 1)12 appeared to be reliable and accurate and could be applied to incidence prediction. Conclusions The proposed prediction model could provide clues to early identification of the JE incidence that is increased abnormally (≥0.4/100 000). According to the predicted Results in 2014, the JE incidence in Xianyang will decline slightly and reach its peak from June to August.
Assuntos
Encefalite Japonesa/epidemiologia , Modelos Biológicos , Estações do Ano , China/epidemiologia , Humanos , IncidênciaRESUMO
It has been well documented that Momordica charantia polysaccharide (MCP) has multiple biological effects such as immune enhancement, anti-oxidation and anti-cancer. However, the potential protective effects of MCP on stroke damage and its relative mechanisms remain unclear. Our present study demonstrated that MCP could scavenge reactive oxygen species (ROS) in intra-cerebral hemorrhage damage, significantly attenuating the neuronal death induced by thrombin in primary hippocampal neurons. Furthermore, we found that MCP prevented the activation of the c-Jun N-terminal protein kinase (JNK3), c-Jun and caspase-3, which was caused by the intra-cerebral hemorrhage injury. Taken together, our study demonstrated that MCP had a neuroprotective effect in response to intra-cerebral hemorrhage and its mechanisms involved the inhibition of JNK3 signaling pathway.
Assuntos
Lesões Encefálicas/tratamento farmacológico , Hemorragia Cerebral/complicações , Proteína Quinase 10 Ativada por Mitógeno/metabolismo , Momordica charantia/química , Fármacos Neuroprotetores/farmacologia , Fitoterapia , Polissacarídeos/farmacologia , Animais , Apoptose/efeitos dos fármacos , Western Blotting , Lesões Encefálicas/etiologia , Lesões Encefálicas/metabolismo , Radicais Livres/metabolismo , Immunoblotting , Técnicas Imunoenzimáticas , Imunoprecipitação , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacosRESUMO
BACKGROUND: CA 19-9 is one of the most frequently used biomarkers for tumors. METHODS: We analyzed the influential factors of the Carbohydrate Antigen 19-9 (CA 19-9) levels in Chinese general population to better interpret the results of the CA 19-9 screening tests. 36,924 apparently healthy individuals and 1,335 patients with gastrointestinal (GI) tumors were involved in this study. Serum CA 19-9 levels were measured using a Roche Cobas E601. RESULTS: The serum CA 19-9 levels in apparently healthy individuals were correlated with age and gender. Its level was positively correlated with the age of males, while it showed a V-shape curve in female populations. This effect could be due to sex hormones, such as prolactin, which were found to have a negative effect on the level of CA 19-9 in the present study. CONCLUSIONS: Our data indicates that gender and age could affect the CA19-9 serum level. We can set up different cut-off values according to the patient's gender and age, which can help us to get a more individualized representation in different populations.
Assuntos
Biomarcadores Tumorais/sangue , Antígeno CA-19-9/sangue , Adolescente , Adulto , Idoso , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
T lymphopenia, occurring in the early phase of sepsis in response to systemic inflammation, is commonly associated with morbidity and mortality of septic infections. We have previously shown that a sufficient number of T cells is required to constrain Toll-like receptors (TLRs) mediated hyperinflammation. However, the underlying mechanisms remains unsolved. Herein, we unveil that CD4+ T cells engage with MHC II of macrophages to downregulate TLR pro-inflammatory signaling. We show further that the direct contact between CD4 molecule of CD4+ T cells or the ectodomain of CD4 (soluble CD4, sCD4), and MHC II of resident macrophages is necessary and sufficient to prevent TLR4 overactivation in LPS and cecal ligation puncture (CLP) sepsis. sCD4 serum concentrations increase after the onset of LPS sepsis, suggesting its compensatory inhibitive effects on hyperinflammation. sCD4 engagement enables the cytoplasmic domain of MHC II to recruit and activate STING and SHP2, which inhibits IRAK1/Erk and TRAF6/NF-κB activation required for TLR4 inflammation. Furthermore, sCD4 subverts pro-inflammatory plasma membrane anchorage of TLR4 by disruption of MHC II-TLR4 raft domains that promotes MHC II endocytosis. Finally, sCD4/MHCII reversal signaling specifically interferes with TLR4 but not TNFR hyperinflammation, and independent of the inhibitive signaling of CD40 ligand of CD4+ cells on macrophages. Therefore, a sufficient amount of soluble CD4 protein can prevent excessive inflammatory activation of macrophages via alternation of MHC II-TLR signaling complex, that might benefit for a new paradigm of preventive treatment of sepsis.
Assuntos
Antígenos CD4 , Sepse , Humanos , Antígenos CD4/metabolismo , Receptor 4 Toll-Like/genética , Lipopolissacarídeos/metabolismo , Macrófagos/metabolismo , Sepse/genética , Sepse/metabolismo , Inflamação/metabolismoRESUMO
Understanding of the mechanism of colorectal carcinogenesis has been gaining momentum for some years on account of its high incidence and impact on the lives of individuals affected. Different genetic abnormalities have been found in colorectal cancers from different sites. For example, proximal colon cancer is usually related to the nucleotide instability pathway, as microsatellite instability (MSI). However, distal colon cancer is usually associated with specific chromosomal instability (CIN). The development of cancer at the rectum, though similar to that at the colon, displays its own unique features. These differences might be partially attributed to different embryological development and physiological circumstances. Environmental factors such as diet and alcohol intake also differ in their role in the development of tumors in the three segments, proximal colon, distal colon, and rectum. "Proximal shift" of colon cancer has been known for some time, and survival rates of colorectal cancer are higher when rectal cancers are excluded, both of which emphasize the three different segments of colorectal cancer and their different properties. Meanwhile, colonic and rectal cancers are distinctive therapeutic entities. The concept of three entities of colorectal cancer may be important in designing clinical trails or therapeutic strategies. However, the dispute about the inconsistency of data concerning the site-specific mechanism of colorectal carcinoma does exist, and more evidence about molecular events of carcinogenesis and targeted therapy needs to be collected to definitely confirm the conception.
Assuntos
Neoplasias Colorretais/metabolismo , Animais , Neoplasias Colorretais/classificação , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Humanos , Estadiamento de Neoplasias , Prognóstico , Fatores de RiscoRESUMO
OBJECTIVE: To evaluate the metabolic characteristics of insulin secretion and insulin sensitivity in isolated impaired fasting glucose (iIFG) and isolated fasting hyperglycemia (IFH) and to clarify the factors responsible for the development of IFH. METHODS: Receiver operating characteristic curve (ROC) analysis was conducted in 1852 subjects. Three groups were classified according to a 75 g oral glucose tolerance test (OGTT): (1) normal glucose tolerance (NGT), n = 557; (2) iIFG, n = 221; (3) IFH, n = 81. The three groups were compared with insulin secretion (insulinogenic index) and insulin sensitivity (insulin sensitivity index). RESULTS: Using ROC analysis, the optimal cut point of fasting plasma glucose (FPG) related to diabetes diagnosis with OGTT was 6.695 mmol/L and the optimal cut point of FPG related to impaired glucose to lerance (IGT) diagnosis with OGTT was 5.590 mmol/L. From NGT to iIFG and IFH in these subjects, the insulinogenic index and insulin sensitivity index showed gradual decrease. CONCLUSION: Subjects with iIFG and IFH exhibit distinctly impaired early-phase insulin secretion and insulin sensitivity, indicating that both reduced insulin secretion and insulin resistance are the determinants of deterioration from NGT to iIFG and IFH.
Assuntos
Diabetes Mellitus Tipo 2/sangue , Hiperglicemia/sangue , Insulina/sangue , Adulto , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/fisiopatologia , Jejum/sangue , Feminino , Teste de Tolerância a Glucose , Humanos , Hiperglicemia/metabolismo , Hiperglicemia/fisiopatologia , Insulina/metabolismo , Resistência à Insulina , Secreção de Insulina , Masculino , Pessoa de Meia-Idade , Curva ROCRESUMO
This study was a cross-sectional case-control study aimed at (1) identifying risk factors contributing to the measles epidemic and (2) evaluating the impacts of measles-containing vaccines (MCVs), with the goal of providing evidence-based recommendations for measles elimination strategies in China. Data on measles cases from 2000 to 2014 were obtained from a passive surveillance system at the Center for Diseases Prevention and Control in Xianyang. The effectiveness of MCVs was evaluated in 357 patients with a vaccination history and 503 healthy randomly selected controls. Patient data were subjected to multivariable logistic regression modeling. From 2005 to 2014, the average incidence of measles in Xianyang was 5.42 cases per 100,000 people. The second MCV dose was highly protective in 8-month-old infants. MCVs in general have been highly protective in 8-month-old infants. Multivariable logistic regression modeling indicated that age (≥2 years vs. <2years), MCV dose 2 vaccination, and MV vaccination were each independently associated with measles case status. In conclusions: A MCV should be administered on time to all age-eligible children, reproductive-age women, and migrant populations, to maximize herd immunity to measles.
Assuntos
Epidemias , Programas de Imunização , Vacina contra Sarampo/administração & dosagem , Sarampo/epidemiologia , Adolescente , Adulto , Estudos de Casos e Controles , Criança , Pré-Escolar , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Incidência , Lactente , Masculino , Sarampo/mortalidade , Fatores de Risco , Estações do Ano , Resultado do Tratamento , Adulto JovemRESUMO
The use of mineral magnetic measurements as a potential pollution proxy is explored as an alternative means of monitoring heavy metal pollution in playground dust in industrial areas. Dust samples were collected from playgrounds in an industrial area in Nanjing. The magnetic properties of the samples were analyzed, and the total and acid-extractable concentrations of heavy metals were measured.Mineral magnetic concentration parameters[mean magnetic susceptibility (χlf) 939.31×10-8 m3·kg-1 and saturation isothermal remanent magnetization (SIRM) 16618.74×10-5 A·m2·kg-1] indicate that the dust samples contain high concentrations of magnetic minerals when compared to the non-industrial zone of the city. High and stable S-ratio values (mean 0.97, standard deviation 0.01) indicate the prominence of ferromagnetic minerals. Low values of anhysteretic remanent magnetization (χARM)/χlf(2.35) and χARM/SIRM (0.12×10-3 m·A-1) indicate predominantly coarse pseudo single domain (PSD) and multi-domain (MD) magnetic grain size assemblages. The playground dust is considered moderately to highly polluted, and the enrichment factor values for Cd, Zn, Cu, and Pb indicate extremely high contamination levels in the playground dust. Mineral magnetic parameters[χlf, SIRM, hard isothermal remanent magnetization (HIRM), χARM, and χARM/SIRM] reveal significant correlations with total and acid-extractable concentrations of the trace metals, and the correlations with total concentrations are stronger. The most significant correlations were found with mineral magnetic concentrations (χARM and SIRM) and total concentrations of the elements Mn, Ni, and Cr and the Tomlinson pollution load index (PLI) (0.69 ≤ r ≤ 0.86, P<0.01). Consistent spatial characteristics between them were also found, showing that the total concentrations of heavy metals and magnetic parameter values are higher in the playgrounds near and downwind of the power plant. Results of a principal component analysis indicate that anthropogenic activities (mainly from coal consumption by power plants) are the main sources for both heavy metals and magnetic minerals. In summary, significant correlations and consistent spatial characteristics between heavy metal contents and magnetic parameters and the same anthropogenic source for heavy metals and magnetic minerals confirm that magnetic parameters could be considered as efficient indicators for heavy metal contamination in the playground dust in industrial areas.
RESUMO
The pollution characteristics and light extinction contribution of water-soluble ions of PM2.5 in Hangzhou were investigated by sampling and laboratory analysis of aerosol samplers in 2013. The water-soluble ions were dominant in PM2.5 and the total mass concentration was 37.5 µg·m-3, accounting for 44.4% of the PM2.5 mass concentration. Water-soluble ions were mainly composed of secondary ions(SO42-,NO3- and NH4+), which accounted for 83.4% of total ions. The highest mass concentrations of PM2.5 and major ions were observed in winter and the lowest in summer. The proportions of water-soluble ions in PM2.5 in summer and autumn were obviously higher than those in winter and spring and proportions of secondary ions in water-soluble ions were very close in each season. The contribution was the greatest to PM2.5 from secondary ions generation caused by fuel combustion and automobile exhaust. The annual average values of SOR and NOR were 0.27 and 0.15 respectively, the conversion rate of SO2 in atmosphere was greater than that of NOx. There was obvious positive correlation between SOR or NOR and humidity which indicated the important contribution of heterogeneous oxidation process to the generation of SO42- and NO3-. The annual average of[NO3-]/[SO42-] was 0.63, and the aerosol pollution was primarily affected by emissions from coal burning. In haze days, with the increase of haze pollution level, the mass concentrations of PM2.5, water-soluble ions, secondary ions as well as SOR and NOR all increased gradually, and the stable weather condition in haze days could efficiently promote the accumulation and secondary conversion of pollutants. There were obvious positive correlations between mass concentrations of PM2.5 and SNA and the atmospheric light extinction coefficient. The IMPROVE formula which was used to calculate the light extinction coefficients of different chemical components could efficiently indicate the tendency of aerosol scattering. The extinction contribution of SNA could reach 60.8%. The extinction coefficient of SNA was the highest in winter and lowest in summer, and its value and contribution proportion both increased gradually as the haze pollution level rose.
RESUMO
Using APS-3321, the atmospheric aerosol number concentrations (0.5-20 µm) were continuously monitored to analyze the characteristics of winter and spring pollution in 2014 in a northern suburb of Nanjing. The average number concentrations were (364.8±297.8) cm-3 and (79.6±62.4) cm-3 in winter and spring, respectively; fine particles (0.5-1.0 µm) accounted for 87.8% and 86.6% of the total, respectively. There were significant variations in number concentration at different periods. The diurnal variations in number concentrations were evident with high concentrations at night and low concentrations during the day. The early peaks were at 07:00 and 09:00, and number concentrations began to increase rapidly starting at 17:00 and 18:00 in winter and spring, respectively. The distribution of the number concentrations was unimodal, with peak sizes between 0.583 and 0.626 µm in winter and less than 0.542 µm in spring. With the increase in relative humidity, aerosol number concentrations increased gradually; at the same time, the peak size moved to a larger diameter which reflected the influence of hygroscopic growth of aerosols. During the total observation period, it reached 83.3% of the proportion of hazy days. The number concentration of particles less than 2.0 µm increased significantly with the increase in the haze pollution level, which was more obvious in winter. In spring, the proportion of fine particles increased with the increase in the haze level but in winter, it decreased during hazy days due to a significant increase in particle size caused by aging. The analysis of the typical pollution process in January indicated that there was a strong correlation between the source of air mass and the surface wind direction. Pollutants transmitted from the northern Jiangsu Province and the accumulation of pollutants due to slow winds were important causations of the pollution process.
RESUMO
The size distribution of particulate was analyzed by the FA-3 9 stage sampler in Northern-suburb of Nanjing from January to November in 2014. First, the monitoring result from FA-3 was compared with the results of the same period obtained from a medium flow size grading sampler (KC-120H) and online monitoring instrument of the Environmental Protection Agency. The data correlation coefficients were all greater than 0.95. The fine particle concentration from FA-3 was lower by 13.9% and 16.6%, while PM10 concentration was higher by 15.2% and 13.3% respectively. However, the deviations were in the acceptable range of atmospheric sampling which could indicate the accurate classification and sampling of particulate for FA-3. Particulate pollution in Northern-suburb Nanjing was serous in which the annual average concentrations of PM1.1, PM2.1 and PM10 were(65.6±37.6), (91.0±54.7) and (168.0±87.0) µg·m-3 respectively; fine particles dominated and most of them had a diameter of less than 1.1 µm. Particle size distribution was bimodal with peaks at 0.43-0.65 and 9-10 µm; the median diameter was 1.83 µm which was in the accumulation mode. In winter, the concentration of fine particle size was higher and in spring the coarse particle size was higher; in summer, the fine particle size concentration was not significantly reduced but coarse particle size was obviously lower than those in other seasons. The differences of particle size distribution in day and at night were very small in coarse segment and in fine segment, the nocturnal concentrations were mostly higher than diurnal concentrations. The precipitation had cleaning effect for each size range of particulate except in summer and the effect was more distinct in fine particle size. In haze days, with the aggravation of haze level, the particle concentration in the diameter range of 0.43-2.1 µm increased gradually while in this segment the particle concentration was significantly negatively correlated with visibility. Using relative humidity of 70% as the demarcation, the particle size distribution changed significantly:when humidity was greater than 70%, mass concentration of particle with a diameter of less than 0.43 µm reduced significantly but that with diameter range of 0.43-2.1 µm increased obviously which should be related to the particle hygroscopic growth. The air mass sources could be divided into four categories in northern-suburb of Nanjing. Air mass from the northwest with rapid transport velocity was the cleanest in which the fine particle size concentration was significantly lower than those in other directions; the air mass from local and surrounding was the most severely polluted with high concentrations in both fine and coarse segment, its transmission distance was short and wind speed was small which contributed greatly to air pollution of Nanjing with probability of occurrence of pollution reaching 73.9%.
RESUMO
It has been demonstrated that Src could modulate NMDA receptor, and PAR1 could also affect NMDAR signaling. However, whether PAR1 could regulate NMDAR through Src under ICH has not yet been investigated. In this study, we demonstrated the role of Src-PSD95-GluN2A signaling cascades in rat ICH model and in vitro thrombin challenged model. Using the PAR1 agonist SFLLR, antagonist RLLFS and Src inhibitor PP2, electrophysiological analysis showed that PAR1 regulated NMDA-induced whole-cell currents (INMDA) though Src in primary cultured neurons. Both in vivo and in vitro results showed the elevated phosphorylation of tyrosine in Src and GluN2A and enhanced interaction of the Src-PSD95-GluN2A under model conditions. Treatment with the PAR1 antagonist RLLFS, AS-PSD95 (Antisense oligonucleotide against PSD95) and Src inhibitor PP2 inhibited the interaction among Src-PSD95-GluN2A, and p-Src, p-GluN2A. Co-application of SFLLR and AS-PSD95, PP2, or MK801 (NMDAR inhibitor) abolished the effect of SF. In conclusion, our results demonstrated that activated thrombin receptor PAR1 induced Src activation, enhanced the interaction among Src-PSD95-GluN2A signaling modules, and up-regulated GluN2A phosphorylation after ICH injury. Elucidation of such signaling cascades would possibly provide novel targets for ICH treatment.
Assuntos
Hemorragia Cerebral/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Quinases da Família src/metabolismo , Animais , Masculino , Neurônios/metabolismo , Fosforilação/fisiologia , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/fisiologia , Trombina/metabolismo , Ativação Transcricional/fisiologia , Tirosina/metabolismo , Regulação para Cima/fisiologiaRESUMO
PURPOSE: CXCL3 and its receptor CXCR2 were considered to play particularly important roles in the progression of malignancies. However, the investigations about CXCL3/CXCR2 axis in prostate cancer have been poorly involved. Herein we firstly reported our studies on the expression and biological roles of CXCL3 and CXCR2 in prostate cancer. METHODS: Expression levels of CXCL3 and CXCR2 in prostate cancer cell lines (PC-3, DU145 and LNCaP), immortalized prostate stromal cell line (WPMY-1) and immortalized prostate epithelial cell line (RWPE-1) were investigated by RT-PCR, ELISA and western blot, whereas expression levels of CXCL3 in a prostate tissue microarray were detected by immunohistochemistry. Cell counting kit-8 and transwell assays were, respectively, utilized to determine the effects of exogenous CXCL3 on the cell proliferation and migration. We further examined whether CXCL3 could regulate the expression of genes correlated with prostate tumorigenesis by RT- PCR. RESULTS: Elevated expression of CXCR2 was detected in DU145, LNCaP and RWPE-1. Moreover, high-level CXCL3 can be secreted by PC-3 and RWPE-1, and CXCL3 protein expression level in tissue microarray is concordant with prostate cancer metastasis. Exogenous CXCL3 does not contribute to proliferation, but has a significant effect on migration of prostate cancer cells and RWPE-1. Finally, our data showed that exogenous CXCL3 can regulate the expression of genes including ERK, TP73, NUMB, BAX and NDRG3. CONCLUSION: Our findings suggest that CXCL3 and its receptor CXCR2 are overexpressed in prostate cancer cells, prostate epithelial cells and prostate cancer tissues, which may play multiple roles in prostate cancer progression and metastasis.
Assuntos
Quimiocinas CXC/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Neoplasias da Próstata/genética , RNA Mensageiro/metabolismo , Receptores de Interleucina-8B/genética , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Quimiocinas CXC/metabolismo , Quimiocinas CXC/farmacologia , Células Epiteliais/metabolismo , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Masculino , Proteínas de Membrana/genética , Proteínas do Tecido Nervoso/genética , Próstata/citologia , Próstata/metabolismo , Neoplasias da Próstata/metabolismo , Receptores de Interleucina-8B/metabolismo , Células Estromais/metabolismo , Proteína Tumoral p73/genética , Proteína X Associada a bcl-2/genéticaRESUMO
OBJECTIVE: To investigate the circadian rhythmicity of adiponectin in patients with Cushing's syndrome and obesity, as well as in normal subjects. The effects of glucocorticoids, insulin and leptin on the secretion of adiponectin were also explored. METHODS: 15 patients with Cushing's syndrome and 10 with obesity as well as 9 normal subjects were recruited and their serum adiponectin, glucocorticoids, insulin and leptin levels were determined 6 times a day (8:00, 12:00, 16:00, 20:00, 24:00, 3:00). RESULTS: Circadian rhythmicity of adiponectin was not observed, but the adiponectin levels in patients with obesity were lower than those in the normal subjects at all 6 time spots. The area under curve (AUC) of serum adiponectin concentrations were significantly negatively correlated with body mass index (BMI, r = 0.46, P < 0.01), waist circumference (r = -0.33, P < 0.05) and insulin AUC (r = -0.36, P < 0.05). A multiple linear regression analysis revealed that BMI and waist circumference were two significant independent parameters of the plasma adiponectin level. The adiponectin levels did not manifest any change after short term dexamethasone administration with both high and low doses, but were obviously decreased after surgery. CONCLUSIONS: Neither long-term endogenous hyperglucocorticoidism nor short-term dexamethasone administration affects the serum adiponectin levels and the serum adiponectin concentrations remain unchanged even with elevated postprandial insulin levels.
Assuntos
Ritmo Circadiano , Síndrome de Cushing/sangue , Hidrocortisona/sangue , Insulina/sangue , Peptídeos e Proteínas de Sinalização Intercelular/sangue , Leptina/sangue , Adiponectina , Adolescente , Adulto , Área Sob a Curva , Índice de Massa Corporal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/sangueRESUMO
OBJECTIVE: To observe the effect of berberine on the differentiation of 3T3-L1 preadipocytes into adipocytes and to elucidate its mechanism. METHODS: 3T3-L1 preadipocytes were cultured and then divided into 7 groups into whose media were added berberine of the concentrations of 0, 0.1, 1, 10, and 100 micro mol/L, 100 nmol/Linsulin, and 10 micro mol/L berberine + 100 nmol/L insulin. The proliferation of 3T3-L1 preadipocytes was detected by MTT method. The accumulation of lipid in the cytoplasm of differentiated adipocytes was observed by oil red O staining. The peroxisome proliferation activated receptor gamma2 (PPARgamma2) mRNA and protein were detected by RT-PCR and Western blotting respectively. RESULTS: MTT method showed that the absorbance at 570 nm of 3T3-L1 preadipocytes increased by 17% (P < 0.01), 36% (P < 0.001), and 22% (P < 0.05) in the groups of 1, 10, and 100 micro mol/L berberine, by 53% (P < 0.0001)in the group of 100 nmol/L insulin, and by 66% in the group of 10 micro mol/L berberine + 100 nmol/L insulin. There were less and smaller lipid droplets in the 3T3-L1 adipocytes treated with berberine as compared with the untreated control cells and only 10% - 20% of the treated cells displayed big lipid drops. RT-PCR showed that berberine significantly reduced the expression of PPARgamma2 mRNA by 48% (P < 0.01) in the course of 3T3-L1 adipocyte differentiation. Western blotting showed that berberine inhibited the expression of PPARgamma2 protein. CONCLUSION: Berberine promotes the proliferation of 3T3-L1 preadipocytes, decreases the accumulation of lipid drops therein, and inhibits the terminal differentiation of adipocyte, which may be associated with its effect on decreasing the expression of PPARgamma2 mRNA and protein, suggesting that berberine has advantages in the treatment of obesity patients with type 2 diabetes.
Assuntos
Adipócitos/citologia , Berberina/farmacologia , Células 3T3-L1 , Animais , Diferenciação Celular/efeitos dos fármacos , Divisão Celular/efeitos dos fármacos , Camundongos , RNA Mensageiro/análise , Receptores Citoplasmáticos e Nucleares/análise , Receptores Citoplasmáticos e Nucleares/genética , Células-Tronco/citologia , Fatores de Transcrição/análise , Fatores de Transcrição/genéticaRESUMO
The accumulation of Pb in urban soils is still apparent in China, and scientific assessment and management of risks from Pb-contaminated soils is necessarily based on contamination levels and extent evaluated accurately. Lead concentration in urban soils has a strong spatial variation and complex spatial structures. Carried out in a single spatial scale, most current investigations cannot comprehensively reveal characteristics of spatial structures, and did not promote more scientific assessment and management of risk. Exploring a new method which can help identify the overall spatial structures is needed. To achieve this aim, this paper firstly investigated the factors linked to the spatial variability of Pb concentration in urban soils, and three major factors were identified: various pollution sources, hierarchical pollution processes and heterogeneous urban landscape. These factors were form a nested hierarchical spatial structure with three spatial levels. Based on the conceptual spatial structure, we proposed a method framework guided by geostatistical theory and focused on linear mixed model (LMM). This proposed framework can divide the nested hierarchical spatial structures of Pb concentration in urban soils into three levels: global trend, random variation with spatial autocorrelation, and outliers. Two recommendations were given to promote the multiple-scale investigation in spatial variation of soil Pb contamination in urban area including: finding more efficient sampling strategy and determining the characteristic scale.