RESUMEN
Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social deficits and repetitive/stereotyped behaviors. Prenatal exposure to valproic acid (VPA) has been reported to induce ASD-like symptoms in human and rodents. However, the etiology and pathogenesis of ASD have not been well elucidated. This study aimed to explore the mechanisms underlying VPA-induced ASD-like behaviors using zebrafish model and investigated whether vitamin A could prevent VPA-induced neurotoxicity. Here, zebrafish embryos were exposed to 0, 25 and 50⯵M VPA from 4 to 96â¯h post fertilization (hpf) and the neurotoxicity was assessed. Our results showed that VPA affected the normal development of zebrafish larvae and induced ASD-like behaviors, including reduced locomotor activity, decreased distance near conspecifics, impaired social interaction and repetitive swimming behaviors. Exposure to VPA decreased the GFP signal in transgenic HuC:egfp zebrafish according to the negative effect of VPA on the expression of neurodevelopmental genes. In addition, VPA enhanced oxidative stress by promoting the production of reactive oxygen species (ROS) and hydrogen peroxide (H2O2) and inhibiting the activity of superoxide dismutase, then triggered apoptosis by upregulation of apoptotic genes. These adverse outcomes were mitigated by vitamin A, suggesting that vitamin A rescued VPA-induced ASD-like symptoms by inhibiting oxidative stress and apoptosis. Overall, this study identified vitamin A as a promising strategy for future therapeutic regulator of VPA-induced ASD-like behaviors.
Asunto(s)
Trastorno del Espectro Autista , Trastorno Autístico , Efectos Tardíos de la Exposición Prenatal , Embarazo , Animales , Femenino , Humanos , Ácido Valproico/toxicidad , Trastorno Autístico/inducido químicamente , Trastorno Autístico/prevención & control , Trastorno Autístico/tratamiento farmacológico , Pez Cebra , Trastorno del Espectro Autista/inducido químicamente , Trastorno del Espectro Autista/prevención & control , Trastorno del Espectro Autista/tratamiento farmacológico , Vitamina A/uso terapéutico , Larva , Peróxido de Hidrógeno , Conducta Social , Conducta Animal , Estrés Oxidativo , Modelos Animales de Enfermedad , Efectos Tardíos de la Exposición Prenatal/inducido químicamenteRESUMEN
Microscale gas chromatography (µGC) systems are miniaturized instruments that typically incorporate one or several microfabricated fluidic elements; such systems are generally well suited for the automated sampling and analysis of gas-phase chemicals. Advanced µGC systems may incorporate more than 15 elements and operate these elements in different coordinated sequences to execute complex operations. In particular, the control software must manage the sampling and analysis operations of the µGC system in a time-sensitive manner; while operating multiple control loops, it must also manage error conditions, data acquisition, and user interactions when necessary. To address these challenges, this work describes the investigation of multithreaded control software and its evaluation with a representative µGC system. The µGC system is based on a progressive cellular architecture that uses multiple µGC cells to efficiently broaden the range of chemical analytes, with each cell incorporating multiple detectors. Implemented in Python language version 3.7.3 and executed by an embedded single-board computer, the control software enables the concurrent control of heaters, pumps, and valves while also gathering data from thermistors, pressure sensors, capacitive detectors, and photoionization detectors. A graphical user interface (UI) that operates on a laptop provides visualization of control parameters in real time. In experimental evaluations, the control software provided successful operation and readout for all the components, including eight sets of thermistors and heaters that form temperature feedback loops, two sets of pressure sensors and tunable gas pumps that form pressure head feedback loops, six capacitive detectors, three photoionization detectors, six valves, and an additional fixed-flow gas pump. A typical run analyzing 18 chemicals is presented. Although the operating system does not guarantee real-time operation, the relative standard deviations of the control loop timings were <0.5%. The control software successfully supported >1000 µGC runs that analyzed various chemical mixtures.
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Objective: To observe the effects of exosomes derived from human umbilical cord mesenchymal stem cells on the proliferation and invasion of pancreatic cancer cells, and to analyze the contents of exosomes and explore the mechanisms affecting pancreatic cancer cells. Methods: Exosomes extracted from human umbilical cord mesenchymal stem cells were added to pancreatic cancer cells BxPC3, Panc-1 and mouse models of pancreatic cancer, respectively. The proliferative activity and invasion abilities of BxPC3 and Panc-1 cells were measured by cell counting kit-8 (CCK-8) and Transwell assays. The expressions of miRNAs in exosomes were detected by high-throughput sequencing. GO and KEGG were used to analyze the related functions and the main metabolic pathways of target genes with high expressions of miRNAs. Results: The results of CCK-8 cell proliferation assay showed that the absorbance of BxPC3 and Panc-1 cells in the hucMSCs-exo group was significantly higher than that in the control group [(4.68±0.09) vs. (3.68±0.01), P<0.05; (5.20±0.20) vs. (3.45±0.17), P<0.05]. Transwell test results showed that the number of invasion cells of BxPC3 and Panc-1 in hucMSCs-exo group was significantly higher than that in the control group (129.40±6.02) vs. (89.40±4.39), P<0.05; (134.40±7.02) vs. (97.00±6.08), P<0.05. In vivo experimental results showed that the tumor volume and weight in the exosomes derived from human umbilical cord mesenchymal stem cells (hucMSCs-exo) group were significantly greater than that in the control group [(884.57±59.70) mm(3) vs. (695.09±57.81) mm(3), P<0.05; (0.94±0.21) g vs. (0.60±0.13) g, P<0.05]. High-throughput sequencing results showed that miR-148a-3p, miR-100-5p, miR-143-3p, miR-21-5p and miR-92a-3p were highly expressed. GO and KEGG analysis showed that the target genes of these miRNAs were mainly involved in the regulation of glucosaldehylation, and the main metabolic pathways were ascorbic acid and aldehyde acid metabolism, which were closely related to the development of pancreatic cancer. Conclusion: Exosomes derived from human umbilical cord mesenchymal stem cells can promote the growth of pancreatic cancer cells and the mechanism is related to miRNAs that are highly expressed in exosomes.
Asunto(s)
Ratones , Animales , Humanos , MicroARNs/metabolismo , Exosomas/genética , Sincalida/metabolismo , Neoplasias Pancreáticas/metabolismo , Carcinoma Ductal Pancreático/genética , Células Madre Mesenquimatosas/metabolismo , Cordón UmbilicalRESUMEN
<p><b>OBJECTIVE</b>To estimate the contribution of known identified risk factors to breast cancer incidence and mortality in China, and provide evidence to support the prevention and control of breast cancer for Chinese females.</p><p><b>METHODS</b>We calculated the proportion of breast cancer attributable to specific risk factors. Data on exposure prevalence were obtained from Meta-analyses and large-scale national surveys of representative samples of the Chinese population. Data on relative risks were obtained from Meta-analyses and large-scale prospective studies. Cancer mortality and incidence were taken from the Third National Death Survey and from cancer registries in China.</p><p><b>RESULTS</b>The first 5 risk factors of breast cancer in China were benign breast disease (RR = 2.62), family history of breast cancer (RR = 2.39), smoking (RR = 1.86), overweight (RR = 1.60) and age at menarche (RR = 1.54). The proportion of breast cancer deaths attributable to reproductive factors, lifestyle factors, benign breast disease, the use of external hormone and family history of breast cancer was 27.84%, 23.55%, 15.09%, 3.60% and 2.49%, respectively. The total population attributable fraction (PAF) was 55.95% for risk factors in our study. Overall, we estimated that 79 862 breast cancer cases and 22 456 deaths were attributed to the five risk factors in China in 2005.</p><p><b>CONCLUSIONS</b>The prevention and control of unhealthy lifestyle factors may significantly reduce the number and death of breast cancer in China.</p>
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Femenino , Humanos , Enfermedades de la Mama , Neoplasias de la Mama , Epidemiología , Genética , China , Epidemiología , Predisposición Genética a la Enfermedad , Menarquia , Metaanálisis como Asunto , Sobrepeso , Factores de Riesgo , FumarRESUMEN
<p><b>OBJECTIVE</b>To draw a chorochromatic atlas of mortality on China Cancer Database in order to display the geographical distribution of selected diseases in China and to identify its demographic and disease-specific patterns in the 1990's.</p><p><b>METHODS</b>The source of data was from nationwide cause-of-death surveys conducted in the 1990's. Standardized rates were computed by direct method using the population age distribution in 1964 as the standard of weights. Inverse distance weight (IDW) was applied as the method of interpolation with the help of Arcview system to draw a choropleth map of cancer mortality.</p><p><b>RESULTS</b>The IDW maps of cancer mortality shows a continuous and smooth variation, especially compared with maps drawn by filling method.</p><p><b>CONCLUSION</b>With the application of inverse distance weight interpolation, it seemed feasible to draw continuous map of cancer on sampling data.</p>