RESUMEN
Spatiotemporal organization of distinct biological processes in cytomimetic compartments is a crucial step towards engineering functional artificial cells. Mimicking controlled bi-directional molecular communication inside artificial cells remains a considerable challenge. Here we present photoswitchable molecular transport between programmable membraneless organelle-like DNA coacervates in a synthetic microcompartment. We use droplet microfluidics to fabricate membraneless non-fusing DNA coacervates by liquid-liquid phase separation in a water-in-oil droplet, and employ the interior DNA coacervates as artificial organelles to imitate intracellular communication via photo-regulated uni- and bi-directional transfer of biomolecules. Our results highlight a promising new route to assembly of multicompartment artificial cells with functional networks.
Asunto(s)
Células Artificiales , Condensados Biomoleculares , Orgánulos/fisiología , ADN , Microfluídica/métodosRESUMEN
Primary liver cancer is the third leading cause of cancer-related death worldwide. Most patients are diagnosed at late stages with poor prognosis; thus, identification of modifiable risk factors for primary prevention of liver cancer is urgently needed. The well-established risk factors of liver cancer include chronic infection with hepatitis B virus (HBV) or hepatitis C virus (HCV), heavy alcohol consumption, metabolic diseases such as obesity and diabetes, and aflatoxin exposure. However, a large proportion of cancer cases worldwide cannot be explained by current known risk factors. Dietary factors have been suspected as important, but dietary aetiology of liver cancer remains poorly understood. In this review, we summarised and evaluated the observational studies of diet including single nutrients, food and food groups, as well as dietary patterns with the risk of developing liver cancer. Although there are large knowledge gaps between diet and liver cancer risk, current epidemiological evidence supports an important role of diet in liver cancer development. For example, exposure to aflatoxin, heavy alcohol drinking and possibly dairy product (not including yogurt) intake increase, while intake of coffee, fish and tea, light-to-moderate alcohol drinking and several healthy dietary patterns (e.g. Alternative Healthy Eating Index) may decrease liver cancer risk. Future studies with large sample size and accurate diet measurement are warranted and need to consider issues such as the possible aetiological heterogeneity between liver cancer subtypes, the influence of chronic HBV or HCV infection, the high-risk populations (e.g. cirrhosis) and a potential interplay with host gut microbiota or genetic variations.
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Dieta Saludable , Dieta/efectos adversos , Neoplasias Hepáticas/epidemiología , Neoplasias Hepáticas/etiología , Adulto , Anciano , Encuestas sobre Dietas , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Observacionales como Asunto , Factores de RiesgoRESUMEN
In this study, we report the relationship between hyperuricemia and hypertension in a middle-aged Chinese population, emphasizing the difference of gender. The cross-sectional study was conducted among 1776 adults aged 45-60 years, who participated in the Hefei Nutrition and Health Study (2012). Hyperuricemia was defined as serum uric acid (SUA)> 420 µmol/l for men, and > 360 µmol/l for women. Hypertension was defined as systolic blood pressure (SBP) ≥ 140 mmHg or diastolic blood pressure (DBP) ≥ 90 mmHg. Anthropometric measurements and biochemical data were collected using standardized procedures. Multivariate logistic regression analysis was performed to determine the relationship between hyperuricemia and hypertension with adjustment of potential confounding factors. Body mass index (BMI), waist circumference (WC), SBP, DBP, fasting glucose, SUA and the prevalence of hyperuricemia and hypertension were significantly higher in male than in female (p < 0.001). Females had significantly higher levels of triglycerides (TG) and high-density lipoprotein (HDL)-cholesterol (5.23 ± 0.87 vs 5.12 ± 1.01, p < 0.05, 1.50 ± 0.37 vs 1.28 ± 0.41, respectively.) than males. Simple correlation analysis showed that SUA was positively associated with WC and TG. In addition, after adjusting for potential confounders, hyperuricemia was associated with increased risk of hypertension in both males and females, with odds ratios (95% CI) of 1.680 (1.110-2.543) and 1.065 (1.012-1.118), respectively. Conclusions: The association of hyperuricemia with hypertension was stronger in males than in females, and middle-aged men with hyperuricemia had greater association with hypertension. Our findings remain to be confirmed in future prospective studies.
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Hipertensión/complicaciones , Hiperuricemia/complicaciones , Pueblo Asiatico , Índice de Masa Corporal , China/epidemiología , Estudios Transversales , Femenino , Humanos , Hipertensión/sangre , Hipertensión/diagnóstico , Hipertensión/epidemiología , Hiperuricemia/sangre , Hiperuricemia/diagnóstico , Hiperuricemia/epidemiología , Lipoproteínas HDL/sangre , Masculino , Persona de Mediana Edad , Factores Sexuales , Triglicéridos/sangre , Ácido Úrico/sangre , Circunferencia de la CinturaRESUMEN
Cortex-like cytoskeleton, a thin layer of cross-linked cytoplasmic proteins underlying the cell membrane, plays an essential role in modulating membrane behavior and cell surface properties. However, bottom-up construction of functional cortex-like cytoskeleton in artificial cells remains a challenge. Here, we present metal-phenolic networks as artificial cortical cytoskeletons in liposome-based artificial cells. The metal-phenolic cytoskeleton-reinforced artificial cells exhibit long-term stability, enhanced resistance to a variety of harsh environments, tunable permeability, and well-controlled morphologies. We anticipate that our stable artificial cell models will stride forward to practical applications of liposome-based microsystem.
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Células Artificiales , Liposomas/metabolismo , Citoesqueleto/metabolismo , Microtúbulos , Membrana Celular/metabolismo , Metales/metabolismoRESUMEN
AIM: To explore novel therapeutic target of cisplatin resistance in human gastric cancer. METHODS: The sensitivity of SGC7901 cells and cisplatin-resistant SGC7901 cells (SGC7901/DDP) for cisplatin were detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay. High-quality total RNA which isolated from SGC7901/DDP cells and SGC7901 cells were used for mRNA microarray analysis. Results were analyzed bioinformatically to predict their roles in the development of cisplatin resistance and the expression of 13 dysregulated mRNAs we selected were validated by quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: SGC7901/DDP cells highly resistant to cisplatin demonstrated by MTT assay. A total of 1308 mRNAs (578 upregulated and 730 downregulated) were differentially expressed (fold change ≥ 2 and P-value < 0.05) in the SGC7901/DDP cells compared with SGC7901 cells. The expression of mRNAs detected by qRT-PCR were consistent with the microarray results. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes pathway and protein-protein interaction analysis demonstrated that the differentially expressed mRNAs were enriched in PI3K-Akt, Notch, MAPK, ErbB, Jak-STAT, NF-kappaB signaling pathways which may be involved in cisplatin resistance. Several genes such as PDE3B, VEGFC, IGFBP3, TLR4, HIPK2 and EGF may associated with drug resistance of gastric cancer cells to cisplatin. CONCLUSION: Exploration of those altered mRNAs may provide more promising strategy in diagnosis and therapy for gastric cancer with cisplatin resistance.
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Antineoplásicos/farmacología , Cisplatino/farmacología , Regulación Neoplásica de la Expresión Génica , Neoplasias Gástricas/genética , Línea Celular Tumoral , Supervivencia Celular , Biología Computacional , Resistencia a Múltiples Medicamentos/genética , Resistencia a Antineoplásicos , Perfilación de la Expresión Génica , Humanos , FN-kappa B/metabolismo , Análisis de Secuencia por Matrices de Oligonucleótidos , Fosfatidilinositol 3-Quinasas/metabolismo , ARN Mensajero/metabolismo , Neoplasias Gástricas/tratamiento farmacológicoRESUMEN
OBJECTIVE: Association of Signal transducers and activators of transcription-4 (STAT4) gene polymorphism with susceptibility to inflammatory bowel disease have been investigated in a number of epidemiological studies, but the results are inclusive. The aim of this meta-analysis was to more precisely estimate the relationship. METHODS: The databases of Pubmed and CBM updated to October, 2014 were retrieved. Random- or fixed-effect model was used to estimate odd radio (OR) and corresponding 95% confidence interval (95%CI) on the basis of heterogeneity. RESULTS: Seven articles containing 2196 Crohn's disease (CD) cases, 1588 ulcerative colitis (UC) cases and 4126 controls were identified. We detected a significant association between STAT4 rs7574865 polymorphism and IBD susceptibility in overall population (GG vs. GT+TT, OR=0.855, 95% CI=0.760-0.962, P=0.009), but not in Caucasian and Asian population, respectively. No association was detected between rs7574865 polymorphism and CD susceptibility in overall, Asian and Caucasian population, respectively. Interestingly, a significant association was detected between rs7574865 with UC susceptibility in overall population (G vs. T, OR=0.881, 95% CI=0.798-0.972, P=0.012; GG vs. GT+TT, OR=0.788, 95% CI=0.679-0.914, P=0.002; GG vs. TT, OR=0.683, 95% CI=0.498-0.937, P=0.018) and Caucasians (GG vs. GT+TT, OR=0.833, 95% CI=0.701-0.990, P=0.038; GG+GT vs. TT, OR=0.667, 95% CI=0.456-0.975, P=0.037; GG vs. TT, OR=0.636, 95% CI=0.433-0.934, P=0.021), respectively, and a possible association was found in Asian population (GG vs. GT+TT, OR=0.709, 95% CI=0.503-0.998, P=0.049). CONCLUSIONS: STAT4 rs7574865 gene is IBD risk factor, and this gene polymorphism is associated with UC susceptibility, especially in Caucasians. To confirm these findings, further studies with more sample size are required for a definitive conclusion.
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Pueblo Asiatico/genética , Predisposición Genética a la Enfermedad , Enfermedades Inflamatorias del Intestino/genética , Polimorfismo de Nucleótido Simple/genética , Factor de Transcripción STAT4/genética , Población Blanca/genética , Biomarcadores/sangre , China/epidemiología , Colitis Ulcerosa/genética , Enfermedad de Crohn/genética , Medicina Basada en la Evidencia , Humanos , Enfermedades Inflamatorias del Intestino/diagnóstico , Enfermedades Inflamatorias del Intestino/etnología , Valor Predictivo de las Pruebas , Factores de Riesgo , Sensibilidad y EspecificidadRESUMEN
To investigate the possible risk factors related to macrosomia. Pregnant women and their newborns (n = 1041) were recruited from a cohort study in Maternal and Child Care Center of Hefei from January 2011 to July 2012. Questionnaires were applied to collect the demographic data besides the medical records. Detailed health records of the entire pregnancy were obtained using retrospective study. Meanwhile the data of neonatal outcomes was prospectively tracked. Associations between exposure risk factors and macrosomia were analyzed using Pearson's chi squared test. Logistic regression models were used to assess the independent association between these potential predictors and macrosomia. The incidence of macrosomia of this cohort was 11.24% of which male: female = 2.55:1. Male incidence (8.07%) of macrosomia was higher than female (3.17%), p < 0.001. Body mass index (BMI) before pregnancy (pre-BMI), maternal height, parity were not independently associated with macrosomia; multiple logistic regression analysis indicated that macrosomia was mainly independently associated with weight gain in pregnancy (OR=1.14, 95% CI [1.10-1.19]), maternal age (OR = 1.09, 95% CI [1.03-1.15]) and gestational age (OR = 1.62, 95% CI [1.31-1.99]), respectively. Our findings indicate that weight gain in pregnancy, maternal age and gestational age should be considered as independent risk factors for macrosomia.
RESUMEN
Epidemiological studies demonstrate a linkage between morbidity and mortality and particulate matter (PM), particularly fine particulate matter (PM2.5) that can readily penetrate into the lungs and are therefore more likely to increase the incidence of respiratory and cardiovascular diseases. The present study investigated the compositions of cooking oil fume (COF)-derived PM2.5, which is the major source of indoor pollution in China. Furthermore, oxidative stress, cytotoxicity, apoptosis, and cell cycle arrest induced by COF-derived PM2.5 in primary fetal alveolar type II epithelial cells (AEC II cells) were also detected. N-acetyl-L-cysteine (NAC), a radical scavenger, was used to identify the role of oxidative stress in the abovementioned processes. Our results suggested that compositions of COF-derived PM2.5 are obviously different to PM2.5 derived from other sources, and COF-derived PM2.5 led to cell death, oxidative stress, apoptosis, and G0/G1 cell arrest in primary fetal AEC II cells. Furthermore, the results also showed that COF-derived PM2.5 induced apoptosis through the endoplasmic reticulum (ER) stress pathway, which is indicated by the increased expression of ER stress-related apoptotic markers, namely GRP78 and caspase-12. Besides, the induction of oxidative stress, cytotoxicity, apoptosis, and cell cycle arrest was reversed by pretreatment with NAC. These findings strongly suggested that COF-derived PM2.5-induced toxicity in primary fetal AEC II cells is mediated by increased oxidative stress, accompanied by ER stress which results in apoptosis.
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Contaminantes Atmosféricos/toxicidad , Puntos de Control del Ciclo Celular , Culinaria , Estrés Oxidativo , Material Particulado/toxicidad , Animales , Apoptosis , Línea Celular , China , Células Epiteliales/metabolismo , Células Epiteliales/fisiología , Pulmón/citologíaRESUMEN
The JAK2/STAT3 signal pathway is an important component of survivor activating factor enhancement (SAFE) pathway. The objective of the present study was to determine whether the JAK2/STAT3 signaling pathway participates in hydrogen sulfide (H2S) postconditioning, protecting isolated rat hearts from ischemic-reperfusion injury. Male Sprague-Dawley rats (230-270 g) were divided into 6 groups (N = 14 per group): time-matched perfusion (Sham) group, ischemia/reperfusion (I/R) group, NaHS postconditioning group, NaHS with AG-490 group, AG-490 (5 µM) group, and dimethyl sulfoxide (DMSO; <0.2%) group. Langendorff-perfused rat hearts, with the exception of the Sham group, were subjected to 30 min of ischemia followed by 90 min of reperfusion after 20 min of equilibrium. Heart rate, left ventricular developed pressure (LVDP), left ventricular end-diastolic pressure (LVEDP), and the maximum rate of increase or decrease of left ventricular pressure (± dp/dt(max)) were recorded. Infarct size was determined using triphenyltetrazolium chloride (TTC) staining. Myocardial TUNEL staining was used as the in situ cell death detection method and the percentage of TUNEL-positive nuclei to all nuclei counted was used as the apoptotic index. The expression of STAT3, bcl-2 and bax was determined by Western blotting. After reperfusion, compared to the I/R group, H2S significantly improved functional recovery and decreased infarct size (23.3 ± 3.8 vs 41.2 ± 4.7%, P < 0.05) and apoptotic index (22.1 ± 3.6 vs 43.0 ± 4.8%, P < 0.05). However, H2S-mediated protection was abolished by AG-490, the JAK2 inhibitor. In conclusion, H2S postconditioning effectively protects isolated I/R rat hearts via activation of the JAK2/STAT3 signaling pathway.
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Sulfuro de Hidrógeno/metabolismo , Poscondicionamiento Isquémico , Janus Quinasa 2/metabolismo , Daño por Reperfusión Miocárdica/metabolismo , Factor de Transcripción STAT3/metabolismo , Animales , Apoptosis , Janus Quinasa 2/análisis , Masculino , Ratas , Ratas Sprague-Dawley , Factor de Transcripción STAT3/análisis , Transducción de Señal , TirfostinosRESUMEN
OBJECTIVE: To find out the differences of dietary patterns among freshmen coming from urban and rural areas that might have influenced their bone mineral density and body mass index (BMI). METHODS: With stratified random sampling method, dietary patterns and their bone mineral density, BMI of 1319 freshmen were studied. RESULTS: (1) The ratios of urban freshmen who chose "western food" pattern (χ(2) = 31.548, P = 0.000; χ(2) = 13.068, P = 0.001), "animal food" pattern (χ(2) = 8.279, P = 0.016; χ(2) = 41.137, P = 0.000) or "calcium food" pattern (χ(2) = 37.254, P = 0.000; χ(2) = 15.651, P = 0.000) were higher than that of rural freshmen, and the ratios of rural freshmen who chose "Chinese traditional" pattern (χ(2) = 36.194, P = 0.000; χ(2) = 25.936, P = 0.000) were higher than that of urban freshmen. (2) The average height, weight, BMI, speed of sound (SOS) of male freshmen from rural areas were lower than that from the city and the differences were statistically significant (P < 0.05). Among those female freshmen, only height and weight were significantly different (P < 0.05). (3) In both rural and urban freshmen, the factor scores of "western food" pattern had a positive correlation with BMI, with the correlation coefficients as 0.187, 0.192, 0.551, 0.465 (P < 0.001). The factor scores of "calcium food" pattern were positively related to bone mineral density (SOS values) with correlation coefficients as 0.680, 0.342, 0.841, 0.786, P < 0.001 respectively. The factor scores on "Chinese traditional" pattern were negatively correlated with BMI, with correlation coefficients as -0.223, -0.093 (P < 0.05) which were positively related to bone mineral density (SOS values) in both rural and urban male freshmen, with correlation coefficients as 0.905, 0.711 (P < 0.001). CONCLUSION: Different dietary patterns chosen by urban and rural freshmen had a significant impact on both bone mineral density and BMI.
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Índice de Masa Corporal , Densidad Ósea , Conducta Alimentaria , Adolescente , China , Femenino , Humanos , Masculino , Población Rural , Estudiantes , Población Urbana , Adulto JovenRESUMEN
Realgar has been used successfully to treat diseases for thousands of years, but its poor water solubility and high toxicity hampered its further medical uses. Here, we first applied transdermal drug delivery system to deliver realgar nanoparticles to investigate its anticancer effect and toxicity in vivo. In this study, MTT assay and flow cytometry analysis demonstrated that realgar significantly suppressed the proliferation and induced apoptosis of B16 melanoma cells in a dose-dependent manner. Transdermal penetration studies in vitro showed realgar nanoparticles could be delivered efficiently through skin. Tests on tumor-bearing C57BL/6 mice displayed that realgar could decrease the tumor volume markedly via transdermal drug delivery compared with the intraperitoneal administration and the control. Hematoxylin-eosin and immunohistochemical staining revealed that it could inhibit angiogenesis. The monitoring of the hepatic injury, body weight, feeding behavior, motor activity, and skin irritation of each animal indicated little toxicity of realgar to mice. The results demonstrated that realgar nanoparticles can be dermally delivered to achieve high efficacy against menaloma in vivo with low toxicity.
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Arsenicales/administración & dosificación , Modelos Animales de Enfermedad , Sistemas de Liberación de Medicamentos/métodos , Melanoma Experimental/tratamiento farmacológico , Nanopartículas/administración & dosificación , Neoplasias Cutáneas/tratamiento farmacológico , Sulfuros/administración & dosificación , Administración Cutánea , Animales , Arsenicales/farmacocinética , Masculino , Melanoma Experimental/metabolismo , Melanoma Experimental/patología , Ratones , Ratones Endogámicos C57BL , Neoplasias Cutáneas/metabolismo , Neoplasias Cutáneas/patología , Sulfuros/farmacocinéticaRESUMEN
The JAK2/STAT3 signal pathway is an important component of survivor activating factor enhancement (SAFE) pathway. The objective of the present study was to determine whether the JAK2/STAT3 signaling pathway participates in hydrogen sulfide (H2S) postconditioning, protecting isolated rat hearts from ischemic-reperfusion injury. Male Sprague-Dawley rats (230-270 g) were divided into 6 groups (N = 14 per group): time-matched perfusion (Sham) group, ischemia/reperfusion (I/R) group, NaHS postconditioning group, NaHS with AG-490 group, AG-490 (5 µM) group, and dimethyl sulfoxide (DMSO; <0.2%) group. Langendorff-perfused rat hearts, with the exception of the Sham group, were subjected to 30 min of ischemia followed by 90 min of reperfusion after 20 min of equilibrium. Heart rate, left ventricular developed pressure (LVDP), left ventricular end-diastolic pressure (LVEDP), and the maximum rate of increase or decrease of left ventricular pressure (± dp/dt max) were recorded. Infarct size was determined using triphenyltetrazolium chloride (TTC) staining. Myocardial TUNEL staining was used as the in situ cell death detection method and the percentage of TUNEL-positive nuclei to all nuclei counted was used as the apoptotic index. The expression of STAT3, bcl-2 and bax was determined by Western blotting. After reperfusion, compared to the I/R group, H2S significantly improved functional recovery and decreased infarct size (23.3 ± 3.8 vs 41.2 ± 4.7%, P < 0.05) and apoptotic index (22.1 ± 3.6 vs 43.0 ± 4.8%, P < 0.05). However, H2S-mediated protection was abolished by AG-490, the JAK2 inhibitor. In conclusion, H2S postconditioning effectively protects isolated I/R rat hearts via activation of the JAK2/STAT3 signaling pathway.