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BACKGROUND: A fetus with increased copy number of chromosome 20 was identified by NIPT. Here we utilize several genetic tests and analyses to illuminate the etiology of such aneuploidy. METHODS: Amniotic fluid cells were extracted from pregnant woman and sent for karyotype and chromosomal microarray analysis (CMA). Trio pedigree analysis was conducted with Chromosome Analysis Suite and uniparental disomy (UPD)-tool software. RESULTS: CMA identified consistent results, which were 2 regions of homozygosity: arr[GRCh37]20p12.2q11.1 (11265096_26266313)hmz and arr[GRCh37]20q11.21q13.2(29510306_54430467)hmz. The trio pedigree analysis discovered that the fetal chromosome 20 was the entire maternal UPD mosaic with isodisomy and heterodisomy. CONCLUSIONS: When a large segment of chromosome is homozygous, appropriate genetic tests are required to find the potential mechanisms for UPD formation.
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Cromosomas Humanos Par 20 , Disomía Uniparental , Embarazo , Femenino , Humanos , Disomía Uniparental/genética , Cromosomas Humanos Par 20/genética , Diagnóstico Prenatal/métodos , Cariotipificación , FetoRESUMEN
This study evaluated the association between inflammatory diets as measured by the Dietary Inflammatory index (DII), inflammation biomarkers and the development of preeclampsia among the Chinese population. We followed the reporting guidelines of the Strengthening the Reporting of Observational Studies in Epidemiology statement for observational studies. A total of 466 preeclampsia cases aged over 18 years were recruited between March 2016 and June 2019, and 466 healthy controls were 1:1 ratio matched by age (±3 years), week of gestation (±1 week) and gestational diabetes mellitus. The energy-adjusted DII (E-DII) was computed based on dietary intake assessed using a seventy-nine item semiquantitative FFQ. Inflammatory biomarkers were analysed by ELISA kits. The mean E-DII scores were -0·65 ± 1·58 for cases and -1·19 ± 1·47 for controls (P value < 0·001). E-DII scores positively correlated with interferon-γ (r s = 0·194, P value = 0·001) and IL-4 (r s = 0·135, P value = 0·021). After multivariable adjustment, E-DII scores were positively related to preeclampsia risk (Ptrend < 0·001). The highest tertile of E-DII was 2·18 times the lowest tertiles (95 % CI = 1·52, 3·13). The odds of preeclampsia increased by 30 % (95 % CI = 18 %, 43 %, P value < 0·001) for each E-DII score increase. The preeclampsia risk was positively associated with IL-2 (OR = 1·07, 95 % CI = 1·03, 1·11), IL-4 (OR = 1·26, 95 % CI = 1·03, 1·54) and transforming growth factor beta (TGF-ß) (OR = 1·17, 95 % CI = 1·06, 1·29). Therefore, proinflammatory diets, corresponding to higher IL-2, IL-4 and TGF-ß levels, were associated with increased preeclampsia risk.
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To examine the association between blood urea nitrogen (BUN) and risk of type 2 diabetes (T2DM) among Chinese adults, we performed an ongoing cohort study of 38578 Chinese adults (56.3% males; average age, 41.6 y) who underwent repeated health check-up examinations between 2009 and 2016 and without T2DM at baseline. During follow-up, incident T2DM cases were identified based on self-report, medication use, measurements of fasting plasma glucose, 2 h post oral glucose, or haemoglobinA1c. 2009 (5.2%) cases confirmed with incident T2DM were identified during median follow-up of 3.1 years. With increasing quartiles of BUN levels, the incidences of T2DM gradually increased with 0.69%, 1.11%, 1.53%, and 1.87% for quartile 1 to quartile 4 (p trend <0.001). Compared with quartile 1, the multivariate-adjusted hazard ratios (HRs) and its 95% confidence intervals (95% CIs) for T2DM risk were 1.16 (0.97-1.38) for quartile 2, 1.28 (1.07-1.51) for quartile 3, and 1.28 (1.08-1.52) for quartile 4 (p trend = 0.005). HR for per each standard deviation increase in BUN level was 1.10 (1.04-1.16) (p trend <0.001). This association tended to be more pronounced in those with a lower body mass index at baseline (p-interaction <0.001). Our results suggested that BUN levels were positively associated with incident T2DM risk among Chinese adults. Future prospective investigations in other populations are necessary to confirm our findings.
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Nitrógeno de la Urea Sanguínea , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/epidemiología , Adulto , Anciano , Pueblo Asiatico/estadística & datos numéricos , Glucemia/análisis , Índice de Masa Corporal , China/epidemiología , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de RiesgoRESUMEN
Findings for the roles of dairy products, Ca and vitamin D on ovarian cancer risk remain controversial. We aimed to assess these associations by using an updated meta-analysis. Five electronic databases (e.g. PubMed and Embase) were searched from inception to 24 December 2019. Pooled relative risks (RR) with 95 % CI were calculated. A total of twenty-nine case-control or cohort studies were included. For comparisons of the highest v. lowest intakes, higher whole milk intake was associated with increased ovarian cancer risk (RR 1·35; 95 % CI 1·15, 1·59), whereas decreased risks were observed for higher intakes of low-fat milk (RR 0·84; 95 % CI 0·73, 0·96), dietary Ca (RR 0·71; 95 % CI 0·60, 0·84) and dietary vitamin D (RR 0·80; 95 % CI 0·67, 0·95). Additionally, for every 100 g/d increment, increased ovarian cancer risks were found for total dairy products (RR 1·03; 95 % CI 1·01, 1·04) and for whole milk (RR 1·07; 95 % CI 1·03, 1·11); however, decreased risks were found for 100 g/d increased intakes of low-fat milk (RR 0·95; 95 % CI 0·91, 0·99), cheese (RR 0·87; 95 % CI 0·76, 0·98), dietary Ca (RR 0·96; 95 % CI 0·95, 0·98), total Ca (RR 0·98; 95 % CI 0·97, 0·99), dietary vitamin D (RR 0·92; 95 % CI 0·87, 0·97) and increased levels of circulating vitamin D (RR 0·84; 95 % CI 0·72, 0·97). These results show that whole milk intake might contribute to a higher ovarian cancer risk, whereas low-fat milk, dietary Ca and dietary vitamin D might reduce the risk.
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Calcio de la Dieta/administración & dosificación , Productos Lácteos , Dieta , Neoplasias Ováricas/epidemiología , Vitamina D/administración & dosificación , Animales , Calcio/sangre , Estudios de Casos y Controles , Estudios de Cohortes , Productos Lácteos/efectos adversos , Dieta/efectos adversos , Femenino , Humanos , Leche/química , Riesgo , Vitamina D/sangreRESUMEN
Cancer-induced bone pain (CIBP) is a challenging medical problem that considerably influences cancer patients' quality of life. Currently, few treatments have been developed to conquer CIBP because of a poor understanding of the potential mechanisms. Our previous work has proved that spinal RANTES (a major ligand for CCR5) was involved in the maintenance of CIBP. In this study, we attempted to investigate whether spinal CCR5 and its downstream PKCγ pathway is involved in the maintenance of CIBP. Inoculation of Walker 256 cells into the tibia could induce a marked mechanical allodynia with concomitant upregulation of spinal CCR5 and p-PKCγ expression from day 6 to day 15 after inoculation. Spinal CCR5 was prominently expressed in microglia, and mechanical allodynia was attenuated by intrathecal injection of DAPTA (a specific antagonist of CCR5) with downregulation of spinal CCR5 and p-PKCγ expression levels at day 15 in inoculated rats. Pre-intrathecal injection of RANTES could reverse the anti-allodynia effects of DAPTA. Intrathecal administration of GF109203X (an inhibitor of PKC) could alleviate mechanical allodynia as well as decrease of spinal p-PKCγ expression level, but no influence on spinal CCR5 level. Our findings suggest that CCR5/PKCγ signaling pathway in microglia may contribute to the maintenance of CIBP in rats.
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Neoplasias Óseas/metabolismo , Dolor en Cáncer/metabolismo , Proteína Quinasa C/metabolismo , Receptores CCR5/metabolismo , Transducción de Señal/fisiología , Animales , Neoplasias Óseas/tratamiento farmacológico , Dolor en Cáncer/tratamiento farmacológico , Inhibidores Enzimáticos/administración & dosificación , Femenino , Indoles/administración & dosificación , Inyecciones Espinales , Maleimidas/administración & dosificación , Proteína Quinasa C/antagonistas & inhibidores , Ratas , Ratas Wistar , Transducción de Señal/efectos de los fármacosRESUMEN
Tumor metastasis to bone can subsequently lead to bone cancer pain (BCP). Currently, BCP is difficult to conquer due to a poor understanding of the potential mechanisms. Several studies have indicated that astrocyte-specific connexin 43 (Cx43) was involved in the neuropathic pain, and Cx43 induced the release of chemokine CXCL12 in bone marrow stromal cells. However, whether spinal Cx43 mediates the production of CXCL12 to participate in the maintenance of BCP is still unknown. Here we showed that Walker 256 tumor cells inoculation into the tibia induced a significant mechanical allodynia, which was accompanied by upregulation of spinal p-Cx43 and CXCL12 expression levels from day 6 to day 18 after inoculation. Spinal Cx43 was mainly expressed in astrocytes, and intrathecal (43)Gap26 (a selective Cx43 blocker) markedly attenuated mechanical allodynia as well as reduced p-Cx43 and CXCL12 expression at day 18 after inoculation. Pre-intrathecal administration of CXCL12 almost abolished the attenuated mechanical allodynia by (43)Gap26. Furthermore, intrathecal injection of anti-CXCL12 neutralizing antibody could ameliorate mechanical allodynia with concomitant inhibition of upregulation of CXCL12 expression, but not influence on p-Cx43 expression. Our results indicate that Cx43 mediates CXCL12 production from spinal dorsal horn in astrocytes to maintain bone cancer pain in rats. These findings may improve our understanding of the underlying mechanisms of BCP and provide a novel target for the treatment of BCP.
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Neoplasias Óseas/fisiopatología , Carcinoma 256 de Walker/fisiopatología , Quimiocina CXCL12/biosíntesis , Conexina 43/metabolismo , Dolor/fisiopatología , Asta Dorsal de la Médula Espinal/metabolismo , Animales , Anticuerpos Neutralizantes/farmacología , Neoplasias Óseas/metabolismo , Carcinoma 256 de Walker/metabolismo , Línea Celular Tumoral , Conexina 43/antagonistas & inhibidores , Conexina 43/inmunología , Femenino , Hiperalgesia/fisiopatología , Dolor/metabolismo , Péptidos/farmacología , Fosforilación , Estimulación Física , Ratas Wistar , Tacto , Regulación hacia ArribaRESUMEN
BACKGROUND: Iron may damage sarcomeric proteins through oxidative stress. We explored the left ventricular (LV) torsional mechanics in patients with beta-thalassaemia major and its relationship to myocardial iron load. Using HL-1 cell and B6D2F1 mouse models, we further determined the impact of iron load on proteolysis of the giant sarcomeric protein titin. METHODS AND RESULTS: In 44 thalassaemia patients aged 25 ± 7 years and 38 healthy subjects, LV torsion and twisting velocities were determined at rest using speckle tracking echocardiography. Changes in LV torsional parameters during submaximal exercise testing were further assessed in 32 patients and 17 controls. Compared with controls, patients had significantly reduced LV apical rotation, torsion, systolic twisting velocity, and diastolic untwisting velocity. T2* cardiac magnetic resonance findings correlated with resting diastolic untwisting velocity. The increments from baseline and resultant LV torsion and systolic and diastolic untwisting velocities during exercise were significantly lower in patients than controls. Significant correlations existed between LV systolic torsion and diastolic untwisting velocities in patients and controls, both at rest and during exercise. In HL-1 cells and ventricular myocardium of B6D2F1 mice overloaded with iron, the titin-stained pattern of sarcomeric structure became disrupted. Gel electrophoresis of iron-overloaded mouse myocardial tissue further showed significant decrease in the amount of titin isoforms and increase in titin degradation products. CONCLUSIONS: Resting and dynamic LV torsional mechanics is impaired in patients with beta-thalassaemia major. Cell and animal models suggest a potential role of titin degradation in iron overload-induced alteration of LV torsional mechanics.
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Hierro/metabolismo , Contracción Miocárdica , Miocardio/metabolismo , Proteínas Quinasas/metabolismo , Talasemia/metabolismo , Función Ventricular Izquierda , Adolescente , Adulto , Animales , Fenómenos Biomecánicos , Estudios de Casos y Controles , Línea Celular , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Ratones , Miocitos Cardíacos/metabolismo , Estudios Prospectivos , Proteolisis , Talasemia/complicaciones , Talasemia/diagnóstico por imagen , Talasemia/fisiopatología , Torsión Mecánica , Ultrasonografía , Adulto JovenRESUMEN
The present study investigated the association between the presence of periodontitis and aortic calcification (AC) risk among Chinese adults. A total of 6059 individuals who underwent regular health check-ups and received a diagnosis of periodontitis between 2009 and 2016 were included. The outcome was AC, assessed by a chest low-dose spiral CT scan. Cox proportional hazards regression analysis was used to assess the association between periodontitis and AC risk after adjusting for several confounders. After a median follow-up period of 2.3 years (interquartile range: 1.03-4.97 years), 843 cases of AC were identified, with 532 (12.13%) and 311 (18.59%) patients in the non-periodontitis group and periodontitis group, respectively. Multivariate analyses demonstrated that, compared with those without periodontitis, the hazard ratio and 95% confidence interval for AC risk in participants with periodontitis was 1.18 (1.02-1.36) (P = .025) in the fully adjusted model. Stratified analyses showed that the positive relationship between periodontitis and AC was more evident in males and participants <65 years of age (pinteraction = .005 and .004, respectively). Our results show that the presence of periodontitis was positively associated with AC among Chinese adults, especially among males and younger participants.
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Calcinosis , Calcificación Vascular , Humanos , Estudios de Cohortes , Periodontitis , China , Radiografía Torácica , Aorta Torácica/diagnóstico por imagen , Calcinosis/diagnóstico por imagen , Calcinosis/etiologíaRESUMEN
Objectives: To quantify the burden and variation trends of cancers in children under 5 years at the global, regional, and national levels from 1990 to 2019. Methods: Epidemiological data for children under 5 years who were diagnosed with any one childhood cancer were obtained from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) from 1990 to 2019. The outcomes were the absolute numbers and rates of incidence, prevalence, mortality, and disability-adjusted life-years (DALYs) for different types of cancer. Results: In 2019, 8,774,979.1 incident cases (95% uncertainty interval [UI]: 6,243,599.2 to11,737,568.5) and 8,956,583.8 (6,446,323.9 to 12,364,520.8) prevalent cases of cancer in children under 5 years were identified worldwide; these cancers resulted in 44,451.6 (36,198.7 to 53,905.9) deaths and 3,918,014.8 (3,196,454.9 to 4,751,304.2) DALYs. From 1990 to 2019, although the numbers of incident and prevalent cases only decreased by -4.6% (-7.0 to -2.2) and -8.3% (-12.6 to -3.4), respectively, the numbers of deaths and DALYs clearly declined by -47.8% (-60.7 to -26.4) and -47.7% (-60.7 to -26.2), respectively. In 2019, the middle sociodemographic index (SDI) regions had the highest incidence and prevalence, whereas the low SDI regions had the most mortality and DALYs. Although all of the SDI regions displayed a steady drop in deaths and DALYs between 1990 and 2019, the low-middle and low SDI regions showed increasing trends of incidence and prevalence. Leukemia remained the most common cancer globally in 2019. From 1990 to 2019, the burdens of leukemia, liver cancer, and Hodgkin's lymphoma declined, whereas the incidence and prevalence of other cancers grew, particularly testicular cancer. Conclusions: The global childhood cancer burden in young children has been steadily decreasing over the past three decades. However, the burdens and other characteristics have varied across different regions and types of cancers. This highlights the need to reorient current treatment strategies and establish effective prevention methods to reduce the global burden of childhood cancer.
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Leucemia , Neoplasias Testiculares , Niño , Preescolar , Carga Global de Enfermedades , Humanos , Incidencia , Masculino , Años de Vida Ajustados por Calidad de VidaRESUMEN
BACKGROUND: Anthracycline has been shown to degrade titin that plays a role in myocardial twisting and untwisting. This study aimed to test the hypothesis that left ventricular (LV) twisting and untwisting motion may be altered in children after anthracycline therapy. METHODS: Thirty-six childhood leukemia survivors aged 15.6 ± 5.5 years and 20 healthy controls aged 16.8 ± 7.7 years (P = 0.54) were studied. LV twisting and untwisting motion was determined using speckle tracking imaging, whereas LV ejection fraction and systolic and diastolic mitral annular velocities were determined respectively by three-dimensional and tissue-Doppler echocardiography. RESULTS: Compared with controls, patients had significantly lower LV ejection fraction (P = 0.01) but similar systolic and diastolic mitral annular velocities (all P > 0.05). Their peak LV torsion (P = 0.003), systolic twisting velocity (P < 0.001), and diastolic untwisting velocity (P = 0.04) were significantly lower than controls, which could be attributable to their reduced apical rotation (P = 0.03) and apical untwisting rate (P = 0.002). For the whole cohort, LV systolic torsion and twisting velocity correlated significantly with apical untwisting rate (P < 0.001) and LV diastolic untwisting velocity (P < 0.001). In patients, none of the twisting or untwisting parameters were found to correlate with cumulative anthracycline dose (all P > 0.05). Twenty-eight (78%) patients had LV ejection fractions ≥50%. Although their systolic and diastolic mitral annular velocities were similar to those of controls, their peak LV torsion (P = 0.005), apical untwisting rate (P = 0.01), and LV systolic twisting velocity (P = 0.001) remained significantly lower. CONCLUSION: Impairment of LV twisting and untwisting motion is evident in children after anthracycline therapy, even in those with "normal" LV ejection fractions.
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Antraciclinas/efectos adversos , Ecocardiografía Doppler/métodos , Ecocardiografía Tridimensional/métodos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Anomalía Torsional/inducido químicamente , Anomalía Torsional/diagnóstico por imagen , Anomalía Torsional/fisiopatología , Disfunción Ventricular Izquierda/inducido químicamente , Disfunción Ventricular Izquierda/diagnóstico por imagen , Disfunción Ventricular Izquierda/fisiopatología , Adolescente , Antraciclinas/uso terapéutico , Estudios de Casos y Controles , Niño , Preescolar , Femenino , Humanos , Interpretación de Imagen Asistida por Computador , Masculino , Sobrevivientes , Adulto JovenRESUMEN
This study aimed to determine the levels of health-related behaviours (physical activity, screen exposure and sleep status) among Chinese students from primary, secondary and high schools during the pandemic of COVID-19, as well as their changes compared with their status before the pandemic. A cross-sectional online survey of 10,933 students was conducted among 10 schools in Guangzhou, China, between 8th and 15th March, 2020. After getting the informed consent from student's caregivers, an online questionnaire was designed and used to obtain time spending on health-related behaviours during the pandemic of COVID-19, as well as the changes compared with 3 months before the pandemic, which was completed by students themselves or their caregivers. Students were stratified by regions (urban, suburban, exurban), gender (boys and girls), and grades (lower grades of primary school, higher grades of primary schools, secondary schools and high schools). Data were expressed as number and percentages and Chi-square test was used to analyse difference between groups. Overall, the response rate of questionnaire was 95.3% (10,416/10,933). The median age of included students was 13.0 (10.0, 16.0) years and 50.1% (n = 5,219) were boys. 41.4%, 53.6% and 53.7% of total students reported less than 15 min per day in light, moderate and vigorous activities and 58.7% (n = 6,113) reported decreased participation in physical activity compared with the time before pandemic. Over 5 h of screen time spending on online study was reported by 44.6% (n = 4,649) of respondents, particular among high school students (81.0%). 76.9% of students reported increased screen time compared with the time before pandemic. Inadequate sleep was identified among 38.5% of students and the proportion was highest in high school students (56.9%). Our study indicated that, during the COVID-19 pandemic, the school closure exerted tremendous negative effects on school-aged children's health habits, including less physical activity, longer screen exposure and irregular sleeping pattern.
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COVID-19/epidemiología , Ejercicio Físico/psicología , Tiempo de Pantalla , Privación de Sueño/epidemiología , Estudiantes/psicología , Adolescente , COVID-19/psicología , Niño , China/epidemiología , Estudios Transversales , Femenino , Humanos , Masculino , Pandemias , Encuestas y CuestionariosRESUMEN
The association between dietary fat intake during pregnancy and the risk of developing preeclampsia has been examined in many epidemiological studies, but the results remain inconsistent. The aim of this study was to clarify this association in pregnant Chinese women. After conducting 1:1 matching, 440 pairs consisting of pregnant women with preeclampsia and hospital-based, healthy pregnant women matched by gestational week (± 1 week) and age (± 3 years) were recruited. A 79-item semi-quantitative food frequency questionnaire administered during face-to-face interviews was used to estimate the participants' dietary intake of fatty acids. We found that the intakes of arachidonic acid (AA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) were inversely associated with the risk of developing preeclampsia. Compared with the lowest quartile intake, the multivariate-adjusted odds ratios (95% confidence interval) of the highest quartile intake were 0.42 (0.26-0.68, p-trend < 0.001) for EPA, 0.52 (0.3-0.83, p-trend = 0.005) for DHA, and 0.41 (0.19-0.88, p-trend = 0.007) for AA. However, we did not observe any significant associations between the intake of total fatty acids, saturated fatty acids, and mono-unsaturated fatty acids and the risk of developing preeclampsia. Our results showed that the dietary intake of long-chain polyunsaturated fatty acids (i.e., EPA, DHA, and AA) may protect pregnant Chinese women against the development of preeclampsia.
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Grasas de la Dieta/efectos adversos , Ácidos Grasos/efectos adversos , Preeclampsia/etiología , Adulto , Ácido Araquidónico/efectos adversos , Estudios de Casos y Controles , Ácido Eicosapentaenoico/efectos adversos , Femenino , Humanos , Embarazo , Factores de Riesgo , Encuestas y CuestionariosRESUMEN
BACKGROUND: αB-crystallin (CRYAB) is a small heat shock protein that is able to inhibit neuroinflammatory responses under various pathological conditions. Some studies have proven that neuroinflammatory mechanisms play important roles in bone cancer pain (BCP). However, whether CRYAB participates in the maintenance of BCP has not yet been examined. METHODS: Walker256 tumour cells were inoculated into the tibia to induce a rat model of BCP. Von Frey hairs were used to measure mechanical allodynia. Immunohistochemistry and western blotting were used to examine the expression level of CRYAB in the spinal dorsal horn. RESULTS: The gradual development of mechanical allodynia was induced by the injection of Walker256 cells into the tibia. The downregulation of spinal CRYAB expression was found in BCP rats. The intrathecal administration of CRYAB (from days 9 to 15 post-inoculation) dose-dependently alleviated mechanical allodynia in BCP rats. Additionally, there were concomitant increases in spinal CRYAB expression and decreases in TNF-α expression. CONCLUSIONS: Spinal CRYAB may participate in the maintenance of BCP in rats. The findings will help to identify new drugs for the management of BCP.
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Neoplasias Óseas/patología , Dolor en Cáncer/fisiopatología , Cadena B de alfa-Cristalina/genética , Animales , Dolor en Cáncer/genética , Relación Dosis-Respuesta a Droga , Regulación hacia Abajo , Femenino , Hiperalgesia/genética , Hiperalgesia/fisiopatología , Ratas , Ratas Wistar , Asta Dorsal de la Médula Espinal/metabolismo , Factor de Necrosis Tumoral alfa/genética , Cadena B de alfa-Cristalina/administración & dosificaciónRESUMEN
Targeted proteomics has advantages over earlier conventional technologies for protein detection. We developed and validated an LC/MRM-MS-based targeted proteomic method combined with immunoaffinity precipitation for the enrichment and detection of low abundance chemerin isoforms in human biofluids. After tryptic digestion, each chemerin isoform was characterized by isoform-specific peptides, and the absolute quantification was achieved by using stable isotope-labeled peptides as internal standards. In serum, follicular fluid and synovial fluid, a total of 6 chemerin isoforms were identified and quantified, among which a novel natural isoform 153Q was discovered for the first time. The relative content of the six chemerin isoforms in human serum was 157S â« 156F â« 158K > 154F ≥ 155A > 153Q in the ratio of 25:17:5:2.5:2.2:1, respectively. The absolute contents were in the range of 88-3.5 ng/mL. This distribution remained consistent among the 3 biofluids analyzed. Total chemerin were found to be increased in both polycystic ovary syndrome (serum and follicular fluid) and rheumatoid arthritis (serum) patients. However, chemerin isoform analysis revealed that only 156F & 157S were increased in the former, while 155A, 156F & 157S were increased in the latter. This demonstrates the potential of this method in detailed characterization of changes in chemerin isoforms that may be of clinical relevance.
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Isótopos , Proteómica , Quimiocinas , Cromatografía Liquida , Femenino , Humanos , Espectrometría de Masas , Isoformas de ProteínasRESUMEN
Cancer-induced bone pain (CIBP) is seriously disruptive to the quality of life in cancer patients, and present therapies are limited. The Bv8/prokineticin 2, a new family of chemokines, has been demonstrated to be involved in inflammatory and neuropathic pain. However, whether it is involved in CIBP remains unclear. This study was designed to examine whether spinal Bv8 was involved in the development of CIBP in rats. A rat CIBP model was constructed by injecting Walker 256 carcinoma cells into the medullary cavity of rat tibia. Tibia inoculation with Walker 256 tumour cells resulted in the development of mechanical hyperalgesia. Compared with sham rats, spinal Bv8 mRNA and protein levels were markedly and time-dependently increased in CIBP rats. Intrathecal administration of Bv8 neutralizing antibody (5 ng) could markedly attenuate pain behaviour as well as up-regulation of spinal TNF-α expression at day 18 after inoculation. Intrathecal pre-treatment with synthetic Bv8 (50 pg) almost completely abolished these effects. These data suggested that spinal Bv8/prokineticin 2 participated in the development of CIBP. Targeting of spinal Bv8 might be a promising strategy for the management of cancer-induced bone pain.
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Neoplasias Óseas/complicaciones , Hormonas Gastrointestinales/fisiología , Neuropéptidos/fisiología , Dolor/etiología , Animales , Western Blotting , Neoplasias Óseas/fisiopatología , Carcinoma 256 de Walker/patología , Modelos Animales de Enfermedad , Ensayo de Inmunoadsorción Enzimática , Femenino , Hormonas Gastrointestinales/análisis , Metástasis de la Neoplasia , Trasplante de Neoplasias , Neuropéptidos/análisis , Dolor/fisiopatología , Dimensión del Dolor , Ratas , Ratas Sprague-Dawley , Reacción en Cadena en Tiempo Real de la Polimerasa , Médula Espinal/química , Factor de Necrosis Tumoral alfa/fisiologíaRESUMEN
Microbial degradation of lignocellulose is one of the key problems that need to be solved urgently in the process of utilizing biomass resource. Bacillus amyloliquefaciens MN-8 is our previously isolated bacterium capable of degrading lignin. To determine the capability of strain MN-8 to degrade lignocellulose of corn straw, B. amyloliquefaciens MN-8 was inoculated and fermented with solid-state corn straw powder-MSM culture medium. The changes in the enzyme activity and degradation products of lignocellulose were monitored in the process of fermentation using the FTIR and GC/MS. The results showed that B. amyloliquefaciens MN-8 could produce lignin peroxidase, manganese peroxidase, cellulase and hemicellulase enzymes. The activities of all these enzymes reached the peak after being incubated for 10-16 days, and the highest enzyme activities were 55.0, 16.7, 45.4 and 60.5 U · g(-1), respectively. After 24 d of incubation, the degradation percentages of lignin, cellulose and hemicellulose were up to 42.9%, 40.6% and 27.1%, respectively. The spectroscopic data by FTIR indicated that the intensities of characteristic absorption peaks of lignin, cellulose and hemicellulose of the corn straw were decreased, indicating that the lignocellulose was degraded partly after being fermented by B. amyloliquefaciens MN-8. GC/MS analysis also demonstrated that strain MN-8 could degrade lignocellulose efficiently. It could depolymerize lignin into some monomeric compounds with retention of phenylpropane structure unit, such as amphetamine, benzene acetone and benzene propanoic acids, by the rupture of ß-O-4 bond connected between lignin monomer, and it further oxidized some monomer compounds into Cα carbonyl compounds, such as 2-amino-1-benzeneacetone and 4-hydroxy-3,5-dimethoxy-acetophenone. The GC/MS analysis of the degradation products of cellulose and hemicellulose showed that there were not only monosaccharide compounds, such as glucose, mannose and galactose, but also some glycolysis products including formic acid, acetic acid, propionic acid, 1,1-ethanediol and 3-hydroxy butyric acid. Our results demonstrated that B. amyloliquefaciens MN-8 is capable of degrading lignocelluse of the corn straw effectively and the degradation capacity depends on the lignocellulase activity.
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Bacillus/enzimología , Lignina/metabolismo , Tallos de la Planta , Zea mays , Proteínas Bacterianas/metabolismo , Biomasa , Reactores Biológicos , Celulasa/metabolismo , Celulosa/metabolismo , Fermentación , Glicósido Hidrolasas/metabolismo , Peroxidasas/metabolismo , Polisacáridos/metabolismoRESUMEN
It has been shown that triptolide has beneficial effects in the treatment of neuropathic pain, but its effects on bone cancer pain (BCP) remain unclear. In this study, we aimed to explore the potential role of spinal regulated activation of normal T cell expressed and secreted (RANTES) in the antinociceptive effects of triptolide on BCP. A BCP model was induced by injecting Walker 256 mammary gland carcinoma cells into the intramedullary space of rat tibia. Intrathecal administration of triptolide (0.5, 1, 2 µg) could dose-dependently alleviate mechanical hyperalgesia and spontaneous pain. In addition, there were also concomitant decreases in RANTES mRNA and protein expression levels in spinal dorsal horn. These results suggest that the antinociceptive effects of triptolide are related with inhibition of spinal RANTES expression in BCP rats. The findings of this study may provide a promising drug for the treatment of BCP.
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Analgésicos/farmacología , Neoplasias Óseas/complicaciones , Quimiocina CCL5/antagonistas & inhibidores , Diterpenos/farmacología , Dolor/tratamiento farmacológico , Fenantrenos/farmacología , Animales , Western Blotting , Carcinoma 256 de Walker , Modelos Animales de Enfermedad , Compuestos Epoxi/farmacología , Femenino , Trasplante de Neoplasias , Dolor/etiología , Dimensión del Dolor , Ratas , Ratas Sprague-Dawley , Reacción en Cadena en Tiempo Real de la Polimerasa , Médula Espinal/metabolismo , Médula Espinal/fisiologíaRESUMEN
The mechanical property of extracellular matrix and cell-supporting substrates is known to modulate neuronal growth, differentiation, extension and branching. Here we show that substrate stiffness is an important microenvironmental cue, to which mouse hippocampal neurons respond and integrate into synapse formation and transmission in cultured neuronal network. Hippocampal neurons were cultured on polydimethylsiloxane substrates fabricated to have similar surface properties but a 10-fold difference in Young's modulus. Voltage-gated Ca(2+) channel currents determined by patch-clamp recording were greater in neurons on stiff substrates than on soft substrates. Ca(2+) oscillations in cultured neuronal network monitored using time-lapse single cell imaging increased in both amplitude and frequency among neurons on stiff substrates. Consistently, synaptic connectivity recorded by paired recording was enhanced between neurons on stiff substrates. Furthermore, spontaneous excitatory postsynaptic activity became greater and more frequent in neurons on stiff substrates. Evoked excitatory transmitter release and excitatory postsynaptic currents also were heightened at synapses between neurons on stiff substrates. Taken together, our results provide compelling evidence to show that substrate stiffness is an important biophysical factor modulating synapse connectivity and transmission in cultured hippocampal neuronal network. Such information is useful in designing instructive scaffolds or supporting substrates for neural tissue engineering.
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Red Nerviosa/fisiología , Neuronas/fisiología , Animales , Canales de Calcio/metabolismo , Señalización del Calcio , Células Cultivadas , Medios de Cultivo , Hipocampo/citología , Ratones , Células PC12 , RatasRESUMEN
BACKGROUND: Altered septal curvature and left ventricular (LV) geometry secondary to right ventricular (RV) dilation render two-dimensional assessment of LV mechanics difficult in repaired tetralogy of Fallot (TOF) patients. The novel three-dimensional (3D) speckle tracking echocardiography enables comprehensive evaluation of true 3D LV mechanics. METHODS AND RESULTS: Seventy-six patients aged 23.6 ± 8.3 years, 55 with isolated repair (group I) and 21 with subsequent pulmonary valve replacement (group II), and 34 healthy controls were studied. Three-dimensional volume datasets were acquired for assessment of LV global and regional 3D strain, systolic dyssynchrony index (SDI), twist, twist gradient (twist/LV length), and ejection fraction. A global performance index was calculated as (global 3D strainâ¢twist gradient)/SDI. The septal curvature and LV eccentricity were determined from the mid-ventricular short-axis. Compared with controls, group I and II patients had significantly reduced LV global 3D strain, LV twist, twist gradient, septal curvature, and global performance index, and greater LV systolic and diastolic eccentricity and SDI (all p<0.05). All but the four apical LV segments in patients had reduced regional 3D strain compared with controls (all p<0.05). Septal curvature correlated with LV global 3D strain (r=0.41, p<0.001), average septal strain (r=0.38, p<0.001), twist (r=0.32, p<0.001), twist gradient (r=0.33, p<0.001), and global performance index (r=0.43, p<0.001). CONCLUSIONS: Adverse 3D LV mechanics as characterized by impaired global and regional 3D systolic strain, mechanical dyssynchrony, and reduced twist is related to reduced septal curvature in repaired TOF patients with and without pulmonary valve replacement.
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Ecocardiografía Tridimensional/métodos , Válvula Pulmonar/fisiopatología , Tetralogía de Fallot/fisiopatología , Disfunción Ventricular Izquierda/fisiopatología , Adolescente , Adulto , Análisis de Varianza , Ecocardiografía Doppler en Color/métodos , Femenino , Ventrículos Cardíacos/diagnóstico por imagen , Ventrículos Cardíacos/fisiopatología , Humanos , Masculino , Válvula Pulmonar/cirugía , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Tetralogía de Fallot/cirugía , Disfunción Ventricular Izquierda/diagnóstico , Adulto JovenRESUMEN
AIMS: Subendocardial layer of the ventricle has been shown to be sensitive to anthracycline damage. This study tested the hypothesis that anthracycline therapy for childhood malignancies has differential impact on deformation and rotation of left ventricular (LV) subendocardial and subepicardial layers and hence transmural myocardial strain and rotation gradients. METHODS AND RESULTS: Thirty-two anthracycline-treated survivors of childhood malignancies aged 19.3 ± 5.4 years and 28 controls were studied. Apical four-chamber and parasternal LV short-axis acquisitions at base, papillary muscle level, and apex were analysed for layer-specific myocardial strain and apical and basal rotation and rotational velocities using two-dimensional speckle tracking echocardiography. Transmural strain and rotation gradients were calculated as differences between peak systolic strain and rotation between the inner and outer layers, respectively. Compared with controls, patients had significantly lower transmural circumferential, but not radial or longitudinal, strain gradients (P< 0.05), accounted by the reduced subendocardial circumferential strain, at all three ventricular levels (all P< 0.05). No significant difference in basal transmural rotation gradient was found between patients and controls (P= 0.32). On the other hand, apical rotation, systolic twisting velocity, and diastolic untwisting velocity were reduced preferentially at the subendocardial layer in patients (all P< 0.05), hence accounting for their significantly reduced transmural rotation gradient compared with controls (P< 0.001). The LV ejection fraction correlated inversely with apical transmural circumferential strain gradient (r= -0.39, P= 0.002) and rotation gradient (r= 0.33, P= 0.01). CONCLUSION: Preferential impairment of subendocardial circumferential deformation and apical rotation with consequential reduction of transmural circumferential strain and rotation gradients occurs in anthracycline-treated survivors of childhood cancers.