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Metastasis is one of the major causes of treatment failure in the patients with colon cancer. The aim of our study is to find key proteins and pathways that drive invasion and metastasis in colon cancer. Eight rounds of selection of cancer cells invading through matrigel-coated chamber were performed to obtain highly invasive colon cancer sublines HCT116-I8 and RKO-I8. Stable Isotope Labeling by Amino Acids in Cell Culture technology was used to identify the differently expressed proteins, and the proteomics data were analyzed by ingenuity pathway analysis. PAK1-PBD immunoprecipitation combined with Western blot were carried out to determine Cdc42 activity, and qRT-PCR and Western blot were used to determine gene expression. The functional role of Cdc42BPA and Cdc42 pathway in colon cancer invasion was studied by loss-of-function experiments including pharmacological blockade, siRNA knockdown, chamber invasion, and WST-1 assays. Human colon cancer tissue microarray was analyzed by immunohistochemistry for overexpression of Cdc42BPA and its correlation with clinicopathological parameters and patient survival outcomes. HCT116-I8 and RKO-I8 cells showed significantly stronger invasive potential as well as decreased E-cadherin and increased vimentin expressions compared with parental cells. The differently expressed proteins in I8 cells compared with parental cells were identified. Bioinformatics analysis of proteomics data suggested that Cdc42BPA protein and Cdc42 signaling pathway are important for colon cancer invasion, which was confirmed by experimental data showing upregulation of Cdc42BPA and higher expression of active GTP-bound form of Cdc42 in HCT116-I8 and RKO-I8 cells. Functionally, pharmacological and genetic blockade of Cdc42BPA and Cdc42 signaling markedly suppressed colon cancer cell invasion and reversed epithelial mesenchymal transition process. Furthermore, compared with adjacent normal tissues, Cdc42BPA expression was significantly higher in colon cancer tissues and further upregulated in metastatic tumors in lymph nodes. More importantly, Cdc42BPA expression was correlated with metastasis and poor survival of the patients with colon cancer. This study provides the first evidence that Cdc42BPA and Cdc42 signaling are important for colon cancer invasion, and Cdc42BPA has potential implications for colon cancer prognosis and treatment.
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Neoplasias del Colon/patología , Proteína Quinasa de Distrofia Miotónica/metabolismo , Transducción de Señal , Proteína de Unión al GTP cdc42/metabolismo , Biomarcadores , Línea Celular Tumoral , Humanos , Invasividad Neoplásica , Pronóstico , ProteómicaRESUMEN
Mycophenolate mofetil (MMF) is an important immunosuppressant used in renal transplantation, and mycophenolic acid (MPA) is the active component released from the ester prodrug MMF. The objective of this study was to investigate the population pharmacokinetics of mycophenolic acid (MPA) following oral administration of MMF in Chinese adult renal transplant recipients and to identify factors that explain MPA pharmacokinetic variability. Pharmacokinetic data for MPA and covariate information were retrospectively collected from 118 patients (79 patients were assigned to the group for building the population pharmacokinetic model, while 39 patients were assigned to the validation group). Population pharmacokinetic data analysis was performed using the NONMEM software. The pharmacokinetics of MPA was best described by a two-compartment model with a first-order absorption rate with no lag time. Body weight and serum creatinine level were positively correlated with apparent clearance (CL/F). The polymorphism in uridine diphosphate glucuronosyltransferase gene, UGT2B7, significantly explained the interindividual variability in the initial volume of distribution (V1/F). The estimated population parameters (and interindividual variability) were CL/F 18.3 L/h (34.2%) and V1/F 27.9 L (21.3%). The interoccasion variability was 13.7%. These population pharmacokinetic data have significant clinical value for the individualization of MMF therapy in Chinese adult renal transplant patients.
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Inmunosupresores/farmacocinética , Trasplante de Riñón , Modelos Biológicos , Ácido Micofenólico/farmacocinética , Administración Oral , Adolescente , Adulto , Anciano , Pueblo Asiatico , Teorema de Bayes , China , Femenino , Glucuronosiltransferasa/genética , Glucuronosiltransferasa/metabolismo , Humanos , Inmunosupresores/administración & dosificación , Inmunosupresores/sangre , Absorción Intestinal , Masculino , Tasa de Depuración Metabólica , Persona de Mediana Edad , Ácido Micofenólico/administración & dosificación , Ácido Micofenólico/sangre , Variantes Farmacogenómicas , Estudios Retrospectivos , Adulto JovenRESUMEN
BACKGROUND: Many late adolescents experience a state of psychological sub-health, requiring early recognition and intervention. This study aims to assess the psychological state of late Chinese adolescents and uncover developmental trend of mental health through network analysis. METHOD: We analyzed data from 9072 Chinese high school adolescents in Shandong Province surveyed in 2020-2021, and divided them into the normal, the suspected, and the abnormal groups based on Symptom Checklist 90 (SCL-90) scores. Network analysis was employed to identify the core symptoms and bridge symptoms across different states. RESULTS: Anxiety and depression were the most central symptoms, without gender differences. Core symptoms, network structure, and network invulnerability varied across different psychological states. The abnormal group exhibited the highest value of natural connectivity, followed by the suspected and normal groups. This pattern extended to bridge networks. While not meeting diagnostic criteria, the suspected group demonstrated abnormalities in network edge invariance and global strength invariance. LIMITATIONS: The cross-sectional design cannot establish causality, and biases in self-report measurements cannot be ignored. CONCLUSION: Compared to traditional scale indicators, network structural characteristics may be a more sensitive assessment indicator.
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Ansiedad , Depresión , Humanos , Adolescente , Femenino , Masculino , China/epidemiología , Depresión/psicología , Depresión/epidemiología , Depresión/diagnóstico , Ansiedad/epidemiología , Ansiedad/psicología , Estudios Transversales , Salud Mental , Pueblos del Este de AsiaRESUMEN
Colorectal cancer (CRC) remains one of the leading causes of cancer-related death worldwide. The poor prognosis of this malignancy is attributed mainly to the persistent activation of cancer signaling for metastasis. Here, we showed that protein tyrosine phosphatase-like A domain containing 1 (PTPLAD1) is down-regulated in highly metastatic CRC cells and negatively associated with poor survival of CRC patients. Systematic analysis reveals that epithelial-to-mesenchymal transition (EMT) and mitochondrial fusion-to-fission (MFT) transition are two critical features for CRC patients with low expression of PTPLAD1. PTPLAD1 overexpression suppresses the metastasis of CRC in vivo and in vitro by inhibiting the Raf/ERK signaling-mediated EMT and mitofission. Mechanically, PTPLAD1 binds with PHB via its middle fragment (141-178 amino acids) and induces dephosphorylation of PHB-Y259 to disrupt the interaction of PHB-Raf, resulting in the inactivation of Raf/ERK signaling. Our results unveil a novel mechanism in which Raf/ERK signaling activated in metastatic CRC induces EMT and mitochondrial fission simultaneously, which can be suppressed by PTPLAD1. This finding may provide a new paradigm for developing more effective treatment strategies for CRC.
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Aminoácidos , Neoplasias del Colon , Humanos , Transición Epitelial-Mesenquimal/genética , Dinámicas Mitocondriales , Prohibitinas , Transducción de Señal , Quinasas rafRESUMEN
Despite both microplastics (MPs) and harmful algae blooms (HABs) may pose a severe threat to the immunity of marine bivalves, the toxification mechanism underlying is far from being fully understood. In addition, owing to the prevalence and sudden occurrence characteristics of MPs and HABs, respectively, bivalves with MP-exposure experience may face acute challenge of harmful algae under realistic scenarios. However, little is known about the impacts and underlying mechanisms of MP-exposure experience on the susceptibility of immunity to HABs in bivalve mollusks. Taking polystyrene MPs and diarrhetic shellfish toxin-producing Prorocentrum lima as representatives, the impacts of MP-exposure on immunity vulnerability to HABs were investigated in the thick-shell mussel, Mytilus coruscus. Our results revealed evident immunotoxicity of MPs and P. lima to the mussel, as evidenced by significantly impaired total count, phagocytic activity, and cell viability of haemocytes, which may result from the induction of oxidative stress, aggravation of haemocyte apoptosis, and shortage in cellular energy supply. Moreover, marked disruptions of immunity, antioxidant system, apoptosis regulation, and metabolism upon MPs and P. lima exposure were illustrated by gene expression and comparative metabolomic analyses. Furthermore, the mussels that experienced MP-exposure were shown to be more vulnerable to P. lima, indicated by greater degree of deleterious effects on abovementioned parameters detected. In general, our findings emphasize the threat of MPs and HABs to bivalve species, which deserves close attention and more investigation.
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Toxinas Marinas , Mytilus , Animales , Toxinas Marinas/toxicidad , Microplásticos/metabolismo , Plásticos/metabolismo , Mytilus/metabolismo , MariscosRESUMEN
Irinotecan-induced hepatotoxicity can cause severe clinical complications in patients; however, the underlying mechanism and factors affecting hepatotoxicity have rarely been investigated. In this cross-sectional study, we screened all clinical, demographic, medication, and genetic variables among 126 patients receiving irinotecan and explored potential associations with the incidence and time to onset of irinotecan-induced hepatotoxicity. Approximately 38.9% of the patients suffered from hepatotoxicity after irinotecan administration. The presence of cardiovascular diseases increases the incidence of hepatotoxicity ≈2.9-fold and doubles the hazard of time to hepatotoxicity. Patients with liver metastasis had a >4-fold higher risk of hepatotoxicity and a 3.5-fold increased hazard of time to hepatotoxicity compared to those without liver metastasis. Patients who took cytochrome P450 (CYP) 3A inducers had a 4.4-fold increased incidence of hepatotoxicity, and furthermore, concomitant use of platinum-based antineoplastics revealed 4.2 times the hazard of time to hepatotoxicity compared to those receiving antimetabolites. The cumulative dose of irinotecan (5-9 cycles) increased hepatotoxicity by 8.5 times. However, the genotypes and phenotypes of UGT1A1*28/*6 failed to be predictive factors of hepatotoxicity. The findings of this study suggest that irinotecan-induced hepatotoxicity is not directly associated with genetic variables but is mostly related to concomitant use of CYP3A4 inducers and platinum, as well as the presence of liver metastasis and cardiovascular disease. Thus, close monitoring of liver function is recommended, especially in patients with liver impairment or using CYP3A inducers and platinum antineoplastic drugs, which may be the best way to prevent hepatotoxicity.
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Antineoplásicos , Enfermedad Hepática Inducida por Sustancias y Drogas , Neoplasias Hepáticas , Antineoplásicos/uso terapéutico , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Enfermedad Hepática Inducida por Sustancias y Drogas/genética , China/epidemiología , Estudios Transversales , Citocromo P-450 CYP3A/genética , Inductores del Citocromo P-450 CYP3A , Interacciones Farmacológicas , Humanos , Irinotecán/efectos adversos , Neoplasias Hepáticas/tratamiento farmacológicoRESUMEN
Most patients experience severe hematological toxicity during treatment with gemcitabine; thus, preventing such toxicity would improve the treatment effects and patient quality of life. We analyzed 13 polymorphisms in the transporters, metabolizing enzymes, targets, and genes involved in DNA damage and the folate pathway among 132 patients treated with gemcitabine and studied their association with the severity of the hematological toxicities. Single-locus analysis showed that the single-nucleotide polymorphisms (SNPs) RRM1 rs12806698 and rs11031918 and DCTD rs7663494 were significantly associated with severe neutropenia, hENT1 rs760370 and hCNT3 rs7867504 and rs4877831 were associated with severe leukopenia, CDA rs2072671, DCTD rs7663494, and WEE1 rs3910384 were associated with severe anemia, and MTHFR rs1801133 was associated with severe thrombocytopenia after stringent Bonferroni correction (P < .0038). The gene-gene interaction analysis identified the overall best models, including a 2-way interaction model (hCNT3 rs7867504 and dCK rs12648166) for severe leukopenia (P = .0022) and a 3-locus model (CDA rs207671, DCTD rs7663494, and WEE1 rs3910384) for severe anemia with a strong synergistic effect (P = .0001). The association with hematological toxicity was further strengthened by the results of a haplotype analysis, in which the homozygous genotype combination of rs3910384 CC, rs2072671 AA, rs12648166 GG, rs7867504 CC, and rs7663494 TT conferred high genetic susceptibility to severe thrombocytopenia. Our results suggest that the gene-gene interaction of gemcitabine metabolic pathway genes and WEE1 contributes to susceptibility to gemcitabine-induced hematological toxicity. Moreover, we propose a promising data-mining analysis approach (generalized multifactor dimensionality reduction) to detect and characterize gene-gene interactions.
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Antimetabolitos Antineoplásicos/efectos adversos , Proteínas de Ciclo Celular/genética , Desoxicitidina/análogos & derivados , Enfermedades Hematológicas/inducido químicamente , Proteínas de Transporte de Membrana/genética , Proteínas Tirosina Quinasas/genética , Anciano , Desoxicitidina/efectos adversos , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Gravedad del Paciente , Polimorfismo de Nucleótido Simple , GemcitabinaRESUMEN
OBJECTIVE: Prior pulmonary tuberculosis (PTB) on chest X-ray (CXR) was commonly found in infertile patients receiving examinations before in vitro fertilization and embryo transfer (IVF-ET). It was unclear whether untreated PTB would affect pregnancy outcomes after IVF-ET. METHOD: We conducted a retrospective cohort study of 14,254 infertile patients who had received IVF-ET at Peking University Third Hospital in 2017. Prior PTB was defined as the presence of signs suggestive of old or inactive PTB on CXR, with or without a clinical TB history. Patients who had prior PTB on CXR but had not received a clinical diagnosis and anti-TB therapy were included for analysis. Live birth, clinical pregnancy, and miscarriage rates were compared between the untreated PTB and non-PTB groups. RESULTS: The untreated PTB group had significantly lower clinical pregnancy (31.7% vs. 38.1%) and live birth (23.8% vs. 30.6%) rates than the non-PTB group (both P < 0.001). Multivariate analysis revealed that untreated PTB was a risk factor for decreased live birth rate [odds ratio ( OR), 0.80; 95% confidence interval ( CI), 0.66-0.98; P = 0.028] in all patients and for increased miscarriage ( OR, 4.19; 95% CI, 1.69-10.39; P = 0.002) and decreased live birth ( OR, 0.45; 95% CI, 0.24-0.83; P = 0.011) rates in patients with unexplained infertility. CONCLUSIONS: Untreated PTB was associated with adverse pregnancy outcomes after IVF-ET, especially in patients with unexplained infertility, highlighting the clinical significance of PTB in this specific patient population.
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Transferencia de Embrión/estadística & datos numéricos , Fertilización In Vitro/estadística & datos numéricos , Infertilidad Femenina/epidemiología , Complicaciones Infecciosas del Embarazo/epidemiología , Resultado del Embarazo/epidemiología , Tuberculosis Pulmonar/epidemiología , Aborto Espontáneo/epidemiología , Adulto , China/epidemiología , Femenino , Humanos , Infertilidad Femenina/diagnóstico por imagen , Infertilidad Femenina/etiología , Nacimiento Vivo/epidemiología , Persona de Mediana Edad , Embarazo , Complicaciones Infecciosas del Embarazo/diagnóstico , Radiografía Torácica , Estudios Retrospectivos , Tuberculosis Pulmonar/complicaciones , Tuberculosis Pulmonar/diagnóstico por imagen , Adulto JovenRESUMEN
This study aimed to screen novel anticancer strategies from FDA-approved non-cancer drugs and identify potential biomarkers and therapeutic targets for colorectal cancer (CRC). Methods: A library consisting of 1056 FDA-approved drugs was screened for anticancer agents. WST-1, colony-formation, flow cytometry, and tumor xenograft assays were used to determine the anticancer effect of azelastine. Quantitative proteomics, confocal imaging, Western blotting and JC-1 assays were performed to examine the effects on mitochondrial pathways. The target protein of azelastine was analyzed and confirmed by DARTS, WST-1, Biacore and tumor xenograft assays. Immunohistochemistry, gain- and loss-of-function experiments, WST-1, colony-formation, immunoprecipitation, and tumor xenograft assays were used to examine the functional and clinical significance of ARF1 in colon tumorigenesis. Results: Azelastine, a current anti-allergic drug, was found to exert a significant inhibitory effect on CRC cell proliferation in vitro and in vivo, but not on ARF1-deficient or ARF1-T48S mutant cells. ARF1 was identified as a direct target of azelastine. High ARF1 expression was associated with advanced stages and poor survival of CRC. ARF1 promoted colon tumorigenesis through its interaction with IQGAP1 and subsequent activation of ERK signaling and mitochondrial fission by enhancing the interaction of IQGAP1 with MEK and ERK. Mechanistically, azelastine bound to Thr-48 in ARF1 and repressed its activity, decreasing Drp1 phosphorylation. This, in turn, inhibited mitochondrial fission and suppressed colon tumorigenesis by blocking IQGAP1-ERK signaling. Conclusions: This study provides the first evidence that azelastine may be novel therapeutics for CRC treatment. ARF1 promotes colon tumorigenesis, representing a promising biomarker and therapeutic target in CRC.
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Factor 1 de Ribosilacion-ADP/metabolismo , Neoplasias del Colon/tratamiento farmacológico , Dinaminas/metabolismo , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Dinámicas Mitocondriales/efectos de los fármacos , Ftalazinas/farmacología , Proteínas Activadoras de ras GTPasa/metabolismo , Factor 1 de Ribosilacion-ADP/genética , Animales , Antialérgicos/farmacología , Apoptosis , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Proliferación Celular , Neoplasias del Colon/metabolismo , Neoplasias del Colon/patología , Dinaminas/genética , Quinasas MAP Reguladas por Señal Extracelular/genética , Femenino , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Persona de Mediana Edad , Pronóstico , Tasa de Supervivencia , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de Xenoinjerto , Proteínas Activadoras de ras GTPasa/genéticaRESUMEN
Metastasis is the main factor of treatment failure in cancer patients, but the underlying mechanism remains to be elucidated and effective new treatment strategies are urgently needed. This study aims to explore novel key metastasis-related microRNAs (miRNAs) in esophageal squamous cell carcinoma (ESCC). By comparing miRNA profiles of the highly metastatic ESCC cell sublines, we established through serial in vivo selection with the parental cells, we found that the expression level of miR-515-3p was lower in ESCC tumor tissues than adjacent normal tissues, further decreased in metastatic tumors, and moreover, markedly associated with advanced stage, metastasis and patient survival. The in vitro and in vivo assays suggested that miR-515-3p could increase the expression of the epithelial markers as well as decrease the expression of the mesenchymal markers, and more importantly, suppress invasion and metastasis of ESCC cells. Mechanistically, we revealed that miR-515-3p directly regulated vimentin and matrix metalloproteinase-3 (MMP3) expression by binding to the coding sequence and 3'untranslated region, respectively. In addition, the data from whole-genome methylation sequencing and methylation-specific PCR indicated that the CpG island within miR-515-3p promoter was markedly hypermethylated in ESCC cell lines and ESCC tumor tissues, which may lead to deregulation of miR-515-3p expression in ESCC. Furthermore, our preclinical experiment provides solid evidence that systemic delivery of miR-515-3p oligonucleotide obviously suppressed the metastasis of ESCC cells in nude mice. Taken together, this study demonstrates that miR-515-3p suppresses tumor metastasis and thus represents a promising prognostic biomarker and therapeutic strategy in ESCC.
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Biomarcadores de Tumor/biosíntesis , Neoplasias Esofágicas/metabolismo , Regulación Neoplásica de la Expresión Génica , Metaloproteinasa 3 de la Matriz/biosíntesis , MicroARNs/biosíntesis , Proteínas de Neoplasias/biosíntesis , ARN Neoplásico/biosíntesis , Vimentina/biosíntesis , Línea Celular Tumoral , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patología , Humanos , Metaloproteinasa 3 de la Matriz/genética , MicroARNs/genética , Metástasis de la Neoplasia , Proteínas de Neoplasias/genética , ARN Neoplásico/genéticaRESUMEN
Lung cancer is the most frequent cancer worldwide with a poor prognosis. Identification of novel cancer targets and useful therapeutic strategies without toxicity are urgently needed. In this study, we screened natural products for anticancer bioactivity in a library consisting of 429 small molecules. We demonstrated for the first time that daurisoline, a constituent of Rhizoma Menispermi, repressed lung cancer cell proliferation by inducing cell cycle arrest at the G1 phase. Furthermore, daurisoline was found not only to suppress the growth of lung tumor xenografts in animals without obvious side effects, but also to inhibit cell migration and invasion. Mechanistically, quantitative proteomics and bioinformatics analyses, Western blotting and qRT-PCR confirmed that daurisoline exerted its anticancer effects by inhibiting the expression levels of ß-catenin and its downstream targets c-myc and cyclin D1. Furthermore, our data from Drug Affinity Responsive Target Stability (DARTS), isothermal titration calorimetry (ITC) and a series of functional assays demonstrated that daurisoline could target HSP90 directly and disrupt its interaction with ß-catenin, therefore increasing the ubiquitin-mediated proteasomal degradation of ß-catenin. This study reveals that daurisoline could be a promising therapeutic strategy for the treatment of lung cancer.
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Antineoplásicos/farmacología , Bencilisoquinolinas/farmacología , Carcinogénesis/efectos de los fármacos , Proteínas HSP90 de Choque Térmico/efectos de los fármacos , Neoplasias Pulmonares/patología , beta Catenina/metabolismo , Animales , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Femenino , Proteínas HSP90 de Choque Térmico/metabolismo , Humanos , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Resistance to tumor-necrosis-factor-related apoptosis-inducing ligand (TRAIL) of cancer cell remains a key obstacle for clinical cancer therapies. To overcome TRAIL resistance, this study identifies curcumol as a novel safe sensitizer from a food-source compound library, which exhibits synergistic lethal effects in combination with TRAIL on non-small cell lung cancer (NSCLC). SILAC-based cellular thermal shift profiling identifies NRH:quinone oxidoreductase 2 (NQO2) as the key target of curcumol. Mechanistically, curcumol directly targets NQO2 to cause reactive oxygen species (ROS) generation, which triggers endoplasmic reticulum (ER) stress-C/EBP homologous protein (CHOP) death receptor (DR5) signaling, sensitizing NSCLC cell to TRAIL-induced apoptosis. Molecular docking analysis and surface plasmon resonance assay demonstrate that Phe178 in NQO2 is a critical site for curcumol binding. Mutation of Phe178 completely abolishes the function of NQO2 and augments the TRAIL sensitization. This study characterizes the functional role of NQO2 in TRAIL resistance and the sensitizing function of curcumol by directly targeting NQO2, highlighting the potential of using curcumol as an NQO2 inhibitor for clinical treatment of TRAIL-resistant cancers.
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Anthropogenic VOC emissions are classified into four sources:industrial, mobile, life, and agricultural. An anthropogenic VOC emission inventory in Jiangmen for 2014 was developed using both "top-down" and "bottom-up" emission factor methods, based on statistical survey data. The results showed that the total anthropogenic VOC emissions in Jiangmen were 75.09 kt. VOC emissions from the industrial, mobile, life, and agricultural sources were 41.37, 19.16, 11.07, and 3.50 kt, respectively, which contributed 55.09%, 25.51%, 14.74%, and 4.65% of the total anthropogenic VOC emissions. Motorcycle manufacturing, container manufacturing, coating, printing ink, manufacturing of paint and similar products, printing and packaging printing, plastics and rubber products, artificial leather manufacturing, leather tanning, burning of fossil fuels, manufacturing of basic chemical raw materials, electronics manufacturing, adhesives manufacturing, and furniture manufacturing are key industries in Jiangmen, each of which emit more than 1000 t of VOCs annually. The main emission sources in Pengjiang, Jianghai, and Heshan are industrial, which account for more than 50% of emissions in each of these districts, whereas the main emission sources in Enping and Taishan are agricultural. Districts and county-level cities will be able to achieve better emission reduction by using the local VOC inventory in the formulation of VOC emission reduction policies.
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Volatile organic compounds (VOCs) are an important source of industrial stench. This study was aimed at sampling and analyzing the stench source and its impact on the sensitive spot residential areas, concentrating on certain automobile manufacturing enterprise. The odor concentration and VOCs species of each vent stack, plant boundary, and sensitive spot in the enterprise were determined for November 15 and 17, 2016 via qualitative and quantitative analysis using the triangle odor bag method and gas pre-concentration system-gas chromatography-mass spectra. The results show that the odor concentrations of all vent stacks in the original equipment manufacturing plant and the engine plant were below the criterion level, those of the plant boundaries in the engine plant were below the limits, and those of the plant boundaries and sensitive spots in the original equipment manufacturing plant exceeded the allowed standards. A total of 54 VOCs species were identified, including aromatics, halogenated compounds, alkanes, alkene, cycloalkanes, ketones, esters, ethers, alcohols, sulfur compounds, and oxygen ring compounds. Halogenated compounds were the most abundant VOCs species, followed by aromatics. As a result, aromatics and halogenated compounds are the representative odorants in automobile making. 1,3-Butadiene and ethyl toluene were selected to be the typical odorants of sensitive spots according to mass concentration, detector odor threshold, and threshold dilution multiples of characteristic VOCs species in sensitive spots. The results show that the majority of characteristic VOCs species were from paint composition through the qualitative analysis based on paint used in coating shops. 1,3-Butadiene, which contributed the most to odor pollution, excluding the impact of other emission sources on sensitive spots, originates from spraying and drying processes of coating shops in the original equipment manufacturer. It is recommended that the enterprise should adopt environmentally friendly paints with low VOCs components or RTO purification equipment with higher processing efficiency to reduce the impact of stench on the sensitive residential areas from automobile making.
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BACKGROUND: Astigmatism is one of the most significant obstacles for achieving satisfactory visual function. This study was to evaluate the influence of astigmatism on contrast sensitivity (CS) and higher-order aberrations. METHODS: CS, accommodation response and wavefront aberration were measured in 113 patients with astigmatism, aged 18 - 36 years. Both single and binocular visual performance were examined under four lighting conditions: photopia, photopia with glare, scotopia and scotopia with glare respectively. Accommodation response was classified as normal, abnormal and low. The contribution of the power and axis of astigmatism to CS, accommodation response and wavefront aberration was analyzed. RESULTS: As the dioptric power of astigmatism increased, the loss of CS spatial frequency changed from high to intermediate, and then to low frequency. CS scores varied at different illuminance levels, descending in the following sequence: photopia, photopia with glare, scotopia, and scotopia with glare. However, the normal accommodation group showed better CS values under photopia with glare than without glare. The range of influenced direction of sine-wave gratings remained mostly at the meridian line of high dioptric power, which would be expanded when optical accommadation attenuated. The patients with symmetrical astigmatism got higher CS scores with binoculus vision than with dominant eye vision, while the patients with asymmetrical astigmatism did this only at scotopia with glare. Among higher-order aberrations, coma aberration, secondary coma aberration and the total higher order aberration were influenced by astigmatism, all of which rising with the power of astigmatism increased. CONCLUSIONS: Reducing astigmatism might improve the performance of visual function. Not only the power of astigmatism should be cut down, but also the binocular axes should be made symmetrically.
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Astigmatismo/fisiopatología , Sensibilidad de Contraste , Adolescente , Adulto , Femenino , Humanos , Masculino , Visión OcularRESUMEN
BACKGROUND: The motive of this study was to investigate the collaboration between MDR1 gene polymorphisms and anesthetic effects following pediatric tonsillectomy. METHODS: All together 178 children undergoing tonsillectomy with preoperative sevoflurane-remifentanil anesthesia were selected. In order to determine MDR1 gene polymorphisms of 3435Câ>âT, 1236Câ>âT, and 2677Gâ>âT/A, polymerase chain reaction-restriction fragment length polymorphism was used. Mean arterial pressure (MAP), diastolic blood pressure (DBP), systolic blood pressure (SBP), and heart rate (HR) at T0 (5 mins after the repose), T1 (0âmin after tracheal intubation), T2 (5 mins after the tracheal intubation), T3 (0âmin after the tonsillectomy), T4 (0âmin after removal of the mouth-gag) and T5 (5âmin after the extubation) were observed. The visual analog scale (VAS), the face, legs, activity, cry, and consolability (FLACC) pain assessment, and Ramsay sedation score were recorded after the patients gained consciousness. The adverse reactions were also observed. RESULTS: As compared to the CTâ+âTT genotype of MDR1 1236Câ>âT, the time of induction, respiration recovery, eye-opening, and extubation of children with the CC genotype was found to be shorter (all Pâ<.05); the MAP, SBP, DBP, and HR were significantly reduced at T5 in children that possessed the CC genotype (all Pâ<.05), the VAS at postoperative 1, 2, 4, and 8âhours and Ramsay sedation score were decreased, while the FLACC score increased (all Pâ<.05). It was found that the adverse reaction rate was lower in children bearing the CC genotype (Pâ<.05). CONCLUSION: It could be concluded that anesthetic effect in patients with the MDR1 1236Câ>âT CC genotype was found to be superior to those carrying the CTâ+âTT genotype.
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Anestésicos/uso terapéutico , Éteres Metílicos/uso terapéutico , Variantes Farmacogenómicas , Piperidinas/uso terapéutico , Subfamilia B de Transportador de Casetes de Unión a ATP/genética , Anestésicos/efectos adversos , Presión Sanguínea/efectos de los fármacos , Presión Sanguínea/genética , Niño , Preescolar , Quimioterapia Combinada , Femenino , Técnicas de Genotipaje , Frecuencia Cardíaca/efectos de los fármacos , Frecuencia Cardíaca/genética , Humanos , Hipnóticos y Sedantes/efectos adversos , Hipnóticos y Sedantes/uso terapéutico , Masculino , Éteres Metílicos/efectos adversos , Dimensión del Dolor , Piperidinas/efectos adversos , Polimorfismo de Nucleótido Simple , Cuidados Preoperatorios , Remifentanilo , Respiración/efectos de los fármacos , Sevoflurano , TonsilectomíaRESUMEN
People with cognitive deficits or executive dysfunction are often overweight or obese. Several human neuroimaging studies have found that executive function (EF) predicts food intake and weight gain; however, fewer studies have investigated the relationship between EF and weight loss. The Stroop task is a classic measure of EF that is used in many neuroimaging studies. In the present work, functional near infrared spectroscopy (fNIRS) data were collected during performance of the Stroop task from a sample of overweight or obese adolescents and young adults (n=31) who participated in a summer fitness and weight loss camp. We assessed the Stroop effect by interference in the reaction time (RT) to visual challenges, and by alterations in levels of oxygenated hemoglobin, as detected by fNIRS. In line with previous studies, we found that the Stroop effect was successfully induced by different visual task conditions among obese/overweight individuals. Moreover, our results reveal that better Stroop task performance is correlated with greater weight loss over a4-weekfitness intervention. Indeed, behavioral data demonstrated that reduced RT interference predicted a greater percentage of weight loss. Moreover, overweight/obese individuals with a greater hemodynamic response in the left ventrolateral and bilateral dorsolateral prefrontal cortex due to the Stroop effect lost more weight during the short-term fitness intervention than participants with lower levels of activation of these neural regions. Overall, our results support a role for prefrontal cortex-mediated EF in influencing food intake and weight loss outcomes in a population of a previously unstudied age.
Asunto(s)
Función Ejecutiva/fisiología , Sobrepeso/psicología , Sobrepeso/terapia , Corteza Prefrontal/fisiopatología , Pérdida de Peso , Adolescente , Adulto , Circulación Cerebrovascular/fisiología , Dieta Reductora , Terapia por Ejercicio , Femenino , Lateralidad Funcional , Humanos , Masculino , Sobrepeso/fisiopatología , Oxihemoglobinas/metabolismo , Estudios Prospectivos , Tiempo de Reacción , Espectroscopía Infrarroja Corta , Test de Stroop , Resultado del Tratamiento , Pérdida de Peso/fisiología , Adulto JovenRESUMEN
6-O-Angeloylenolin (6-OA), a sesquiterpene lactone isolated from Centipeda minima (L.) A. Br. (Compositae), has been used to treat respiratory diseases for centuries. However, whether and how 6-OA exerts anticancer effects against lung cancer remains to be elucidated. In this study, we showed that 6-OA markedly suppressed the cell viability and colony formation of lung cancer cells H1299 and A549, with no significant toxic effect on non-cancer cells HBE. Annexin V/7-AAD assay revealed that 6-OA induced cell apoptosis in dose- and time-dependent manners, which was further confirmed by the increased expression of cleaved caspase-3. To uncover the molecular mechanism how 6-OA exerts its anticancer effects, SILAC quantitative proteomics was performed to identify 6-OA-regulated proteins in lung cancer cells. Ingenuity Pathway Analysis revealed that these 6-OA-regulated proteins were mainly involved in Nrf2-mediated oxidative stress response, which was confirmed by the nuclear translocation of Nrf2 upon 6-OA treatment. Moreover, we found that 6-OA stimulated the accumulation of reactive oxygen species (ROS), whereas inhibition of ROS generation with N-acetyl l-cysteine could block the 6-OA-induced anticancer effects. Furthermore, blockade of cellular anti-oxidative system by Nrf2 knockdown significantly augmented the 6-OA-induced apoptosis. Taken together, we demonstrated that 6-OA exerts its anticancer effects by generating ROS, and inhibition of Nrf2 anti-oxidative system potentiated these effects. These results suggest that 6-OA may be used to treat lung cancer, with better outcome by combining with Nrf2 inhibitor to block Nrf2 pathway.
Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Antineoplásicos/uso terapéutico , Lactonas/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Factor 2 Relacionado con NF-E2/antagonistas & inhibidores , Sesquiterpenos/uso terapéutico , Adenocarcinoma/patología , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Humanos , Lactonas/farmacología , Neoplasias Pulmonares/patología , Especies Reactivas de Oxígeno/metabolismo , Sesquiterpenos/farmacologíaAsunto(s)
Neoplasias Colorrectales , Quinasas MAP Reguladas por Señal Extracelular , Glicoproteínas de Membrana/metabolismo , Neoplasias Colorrectales/genética , Progresión de la Enfermedad , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Humanos , Péptidos y Proteínas de Señalización Intracelular/genética , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Transducción de Señal/genética , Proteínas de Unión al GTP rab5/metabolismoRESUMEN
AIM: To investigate the pharmacokinetics of mycophenolic acid (MPA), an active metabolite of mycophenolate mofetil (MMF) in Chinese adult liver transplant patients. METHODS: Thirty-eight liver transplant patients (male 30, female 8) receiving MMF 1.0 g, twice daily in accordance with the recommended regimen were included in this study. Plasma MPA concentrations were measured by high performance liquid chromatography at 0.5, 1, 1.5, 2, 4, 6, 8, 10 and 12 h after the administration of a single dose. Pharmacokinetic parameters were calculated with 3P97 software. RESULTS: The plasma MPA concentration-time curve was characterized with an early sharp peak reached at 0.5 - 6.0 h after oral administration. And in some patients there was a small second peak due to enterohepatic circulation of mycophenolic acid glucuronide (MPAG), which underwent deglucuronidation and re-absorption as MPA at 4 to 12 h postdose. The mean peak plasma concentration (C(max)) and area under concentration-time curve (AUC(0-12 h)) were (12 +/- 7) microg x mL(-1) and (44 +/- 16) microg x h x mL(-1), respectively. However, a large variability of pharmacokinetic parameters existed in these patients. CONCLUSION: In view of the inter-individual variability of MMF pharmacokinetics, plasma MPA concentration should be monitored routinely after MMF administration for individual patient.