Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 46
Filtrar
1.
Environ Pollut ; 289: 117899, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34358865

RESUMO

To prevent the spread of the COVID-19 epidemic, the Chinese megacity Wuhan has taken emergent lockdown measures starting on January 23, 2020. This provided a natural experiment to investigate the response of air quality to such emission reductions. Here, we decoupled the influence of meteorological and non-meteorological factors on main air pollutants using generalized additive models (GAMs), driven by data from the China National Environmental Monitoring Center (CNEMC) network. During the lockdown period (Jan. 23 - Apr. 8, 2020), PM2.5, PM10, NO2, SO2, and CO concentrations decreased significantly by 45 %, 49 %, 56 %, 39 %, and 18 % compared with the corresponding period in 2015-2019, with contributions by S(meteos) of 15 %, 17 %, 13 %, 10 %, and 6 %. This indicates an emission reduction of NOx at least 43 %. However, O3 increased by 43 % with a contribution by S(meteos) of 6 %. In spite of the reduced volatile organic compound (VOC) emissions by 30 % during the strict lockdown period (Jan. 23 - Feb. 14, 2020), which likely reduced the production of O3, O3 concentrations increased due to a weakening of the titration effect of NO. Our results suggest that conventional emission reduction (NOx reduction only) measures may not be sufficient to reduce (or even lead to an increase of) surface O3 concentrations, even if reaching the limit, and VOC-specific measures should also be taken.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , COVID-19 , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Poluição do Ar/prevenção & controle , China , Controle de Doenças Transmissíveis , Monitoramento Ambiental , Humanos , Material Particulado/análise , SARS-CoV-2
2.
J Cancer Res Ther ; 17(3): 790-796, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34269315

RESUMO

Objectives: The objective of the study is to provide an efficient and practical screening strategy to distinguish a broader spectrum of Lynch syndrome (LS) and LS mimics-associated colorectal cancer (CRC), including Lynch-like syndrome (LLS), constitutional mismatch repair-deficiency, familial CRC type X (FCCTX), and polymerase proofreading-associated polyposis syndrome. Materials and Methods: 1294 cases of CRC samples were detected mismatch repair (MMR) status using immunohistochemistry (IHC) staining, in which the cases with MLH1-deficient CRC underwent BRAF mutation analysis by IHC. Following the personal and/or family history survey, next-generation sequencing (NGS) was used to detect gene variants. Results: 1294 CRC patients were dichotomized into tumors caused by a deficient MMR (dMMR) system and a proficient MMR (pMMR) system after MMR status analysis. 45 patients with suspected sporadic dMMR CRC were then separated from MLH1-deficient CRC though BRAF mutation status analysis by IHC. Following the personal and/or family history survey for 1294 patients, as well as germline genetic testing by NGS, 34 patients were diagnosed as LS (8 cases), SLS (13 cases), LLS ( 6 cases), FCCTX (3 cases), and sporadic CRC (4 cases). Conclusions: Our screening strategy, which consists of clinical and molecular analyses, is expected to improve the screening efficiency and management for the LS and LS mimics.

3.
Int J Pharm ; 605: 120799, 2021 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-34126176

RESUMO

This research aimed to overcome the current challenges in the application of natural carotenoid antioxidants, such as their complex preparation processes, low bioavailability and poor drug stability. Herein, a mechanochemical method was used to prepare an inclusion complex (IC) that self-assembles into micelles in aqueous solution and achieves solid-phase loading of astaxanthin (AST). The NMR analysis, thermodynamics study, particle size analysis and electron microscopy image results showed that AST, hydroxypropyl ß-cyclodextrin (HPß-CD) and glyceryl monostearate (GMS) formed self-assembled micelles and maintained good stability in aqueous solution. The antioxidant performance experiments showed that the formation of IC increases free radical scavenging activity. The pharmacokinetic studies showed that the bioavailability of the astaxanthin inclusion complex increased 4-fold. The tissue distribution experiments showed that the astaxanthin inclusion complex targets the liver to exert its antioxidant effects. The proposed method uses an innovative preparation technology to produce an efficient drug delivery system without solvents, and it exerts powerful antioxidant activity against astaxanthin.


Assuntos
Antioxidantes , Micelas , 2-Hidroxipropil-beta-Ciclodextrina , Glicerídeos , Solubilidade , Xantofilas
4.
Pharm Res ; 38(4): 693-706, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33754258

RESUMO

PURPOSE: This study aims to overcome the challenges of the current oral targeted drug delivery system, such as the complex preparation process, poor biocompatibility, and delayed drug release. METHODS: Here, a non-covalent polymer hydrogel was prepared using the mechanochemical method, and the solid phase loading of 5-amino salicylic acid (5-ASA) was realized. RESULTS: The results obtained from the thermodynamics study, particle size analysis, and electron microscopy show that chitosan (CS) and sodium alginate (SA) form a pH-sensitive hydrogel under the mechanochemical force and also maintain good stability in aqueous solution. Fluorescent tracers study showed that the pH-sensitive hydrogel could achieve the targeted drug release in the colon and the retention time was over 12 h. Next, in vivo efficacy studies, change in mice body weight, DAI (disease activity index) score, thymus, and spleen index, and the diseased state of the mice colon revealed that the pH-sensitive hydrogel is an improved drug delivery system over 5-ASA API commercial preparations as observed in the efficacy and toxicological studies. CONCLUSION: This method uses an innovative preparation technology that without the need of cross-linking agent to produce an efficient colon-targeted drug delivery system for the treatment of ulcerative colitis.


Assuntos
Colite Ulcerativa/tratamento farmacológico , Portadores de Fármacos/química , Composição de Medicamentos/métodos , Hidrogéis/química , Mesalamina/administração & dosagem , Administração Oral , Alginatos , Animais , Disponibilidade Biológica , Química Farmacêutica/métodos , Quitosana/química , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/imunologia , Colite Ulcerativa/patologia , Colo/efeitos dos fármacos , Colo/imunologia , Colo/patologia , Sulfato de Dextrana/administração & dosagem , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Liberação Controlada de Fármacos , Humanos , Concentração de Íons de Hidrogênio , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/imunologia , Mucosa Intestinal/patologia , Masculino , Mesalamina/farmacocinética , Camundongos , Tamanho da Partícula , Ratos
5.
Diagn Pathol ; 16(1): 14, 2021 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-33612108

RESUMO

BACKGROUND: Succinate dehydrogenase deficient gastrointestinal stromal tumors (SDH-deficient GISTs), which lack KIT or PDGFRA mutations demonstrate unique clinical and pathological features, and they respond poorly to standard targeted therapy. We herein present a novel case of SDH-deficient GIST in a three-month-old infant's colon mesentery, and he is the youngest patientto date. CASE PRESENTATION: The infantpresented with complaints of blood in the stool. CT showed a 6.3 × 4.6 cm mass in the left lower retroperitoneal. Complete resection of tumor and segmental bowel resection was performed without regional lymphadenectomy. Histologically, tumor cells were distinctive in their multinodular colon wall involvement with interspersed tracts of colon wall smooth muscle. The tumor was composed mainly of epithelioid cells. Immunohistochemically, the tumor cells were positive for Vim, CD117, PDGFR, while negative for SDHB. Mutational analysis showed a synonymous mutation for SDHB and wild-type for KIT and PDGFRA. Two months after surgery, metastases were found and Imatinib was administered. Unfortunately, the disease continued to progress, and the infant died 5 months after surgery. CONCLUSIONS: SDH-deficient GISTs comprise a subgroup of a relatively rare tumor type and show a number of clinically and biologically unique features, especially for infants. It is of great importance to developing new therapeutic targets and novel specific drugs.


Assuntos
Tumores do Estroma Gastrointestinal/genética , Tumores do Estroma Gastrointestinal/patologia , Succinato Desidrogenase/deficiência , Análise Mutacional de DNA/métodos , Tumores do Estroma Gastrointestinal/diagnóstico , Mutação em Linhagem Germinativa , Humanos , Lactente , Mutação/genética , Proteínas Proto-Oncogênicas c-kit/genética , Proteínas Proto-Oncogênicas c-kit/metabolismo , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/genética , Succinato Desidrogenase/metabolismo
6.
J Am Heart Assoc ; 10(2): e018633, 2021 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-33410330

RESUMO

Background Unruptured intracerebral aneurysm wall enhancement (AWE) on vessel wall magnetic resonance imaging scans may be a promising predictor for rupture-prone intracerebral aneurysms. However, the pathophysiology of AWE remains unclear. To this end, the association between AWE and histopathological changes was assessed in this study. Methods and Results A total of 35 patients with 41 unruptured intracerebral aneurysms who underwent surgical clipping were prospectively enrolled. A total of 27 aneurysms were available for histological evaluation. The macroscopic and microscopic features of unruptured intracerebral aneurysms with and without enhancement were assessed. The microscopic features studied included inflammatory cell invasion and vasa vasorum, which were assessed using immunohistochemical staining with CD68, CD3, CD20, and myeloperoxidase for the former and CD34 for the latter. A total of 21 (51.2%) aneurysms showed AWE (partial AWE, n=7; circumferential AWE, n=14). Atherosclerotic and translucent aneurysms were identified in 17 and 14 aneurysms, respectively. Aneurysm size, irregularity, and atherosclerotic and translucent aneurysms were associated with AWE on univariate analysis (P<0.05). Multivariate logistic regression analysis showed that atherosclerosis was the only factor significantly and independently associated with AWE (P=0.027). Histological assessment revealed that inflammatory cell infiltration, intraluminal thrombus, and vasa vasorum were significantly associated with AWE (P<0.05). Conclusions Though AWE on vessel wall magnetic resonance imaging scans may be associated with the presence of atherosclerotic lesions in unruptured intracerebral aneurysms, inflammatory cell infiltration within atherosclerosis, intraluminal thrombus, and vasa vasorum may be the main pathological features associated with AWE. However, the underlying pathological mechanism for AWE still needs to be further studied.


Assuntos
Artérias Cerebrais , Aneurisma Intracraniano , Imageamento por Ressonância Magnética/métodos , Placa Aterosclerótica , Procedimentos Cirúrgicos Vasculares/métodos , Angiografia Cerebral/métodos , Artérias Cerebrais/diagnóstico por imagem , Artérias Cerebrais/patologia , Correlação de Dados , Feminino , Humanos , Imuno-Histoquímica , Inflamação/diagnóstico por imagem , Inflamação/patologia , Aneurisma Intracraniano/diagnóstico por imagem , Aneurisma Intracraniano/patologia , Aneurisma Intracraniano/cirurgia , Masculino , Microcirurgia/métodos , Pessoa de Meia-Idade , Placa Aterosclerótica/diagnóstico por imagem , Placa Aterosclerótica/patologia , Trombose/diagnóstico por imagem , Vasa Vasorum/diagnóstico por imagem
7.
Acta Pharmacol Sin ; 42(1): 160-170, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32541921

RESUMO

Sorafenib is the first-line treatment of advanced hepatocellular carcinoma (HCC). However, there is a lack of validated biomarkers to predict sorafenib sensitivity. In this study we investigated the role of ACSL4, a positive-activating enzyme of ferroptosis, in sorafenib-induced cell death and HCC patient outcome. We showed that ACSL4 protein expression was negatively associated with IC50 values of sorafenib in a panel of HCC cell lines (R = -0.952, P < 0.001). Knockdown of ACSL4 expression by specific siRNA/sgRNA significantly attenuated sorafenib-induced lipid peroxidation and ferroptosis in Huh7 cells, and also rescued sorafenib-induced inhibition of xenograft tumor growth in vivo. We selected 29 HCC patients with surgery as primary treatment and sorafenib as postoperative adjunct therapy from a hospital-based cohort. A high proportion (66.7%) of HCC patients who had complete or partial responses to sorafenib treatment (according to the revised RECIST guideline) had higher ACSL4 expression in the pretreated HCC tissues, compared with those who had stable or progressed tumor growth (23.5%, P = 0.029). Since ACSL4 expression was independent of sorafenib treatment, it could serve as a useful predictive biomarker. Taken together, this study demonstrates that ACSL4 is essential for sorafenib-induced ferroptosis and useful for predicting sorafenib sensitivity in HCC. This study may have important translational impacts in precise treatment of HCC.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Coenzima A Ligases/metabolismo , Neoplasias Hepáticas/tratamento farmacológico , Sorafenibe/uso terapêutico , Animais , Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Coenzima A Ligases/genética , Ferroptose/efeitos dos fármacos , Técnicas de Inativação de Genes , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Masculino , Camundongos Endogâmicos BALB C , Prognóstico , Ensaios Antitumorais Modelo de Xenoenxerto
8.
J Craniofac Surg ; 31(8): 2360-2363, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33136891

RESUMO

BACKGROUND: Gene alterations are very vital when it comes to the molecular pathogenesis of glioma. In this study, there was the design of the probable candidate genes in the glioma. METHODS: Gene Expression Omnibus (GEO) database data sets of glioma tissue were retrieved and the differentially expressed genes (DEGs) from the individual microarray were merged. The following were performed: Gene Ontology; enrichment analysis; Kyoto Encyclopedia of Genes and Genomes (KEGG); pathway analysis; protein-protein interaction networks analysis. RESULTS: The following were selected: 4 GEO data sets that included 370 high-grade glioma samples as well as 169 low-grade glioma samples. Identification of a total of 174 DEGs was done. Out of the identified DEGs, 82 were upregulated and 92 were downregulated genes. According to the Gene Ontology analysis, the primary biologic focus of DEGs included passive transmembrane transporter activity, regulation of channel activity, as well as the revelation that the biologic roles of DEGs aimed primarily on regulating channel activity, as well as the monovalent inorganic cation transmembrane transporter activity. The most significant pathway in KEGG analysis was PI3K-AKT signaling pathway. Some of the significant hub genes as per the protein-protein interaction network analysis included CDC20, NDC80, DLGAP5, CENPF, CENPE, ASPM, TPX2, TOP2A, RRM2, and PRC1. CONCLUSION: From this study, it is evidenced that the use of integrated bioinformatics analyses in screening for pathways and DEGs in glioma can help us understand the clinical significance of understanding glioma, the molecular mechanism that underlies the development of glioma, as well as the provision of an effective target to treat glioma.


Assuntos
Glioma/genética , Glioma/metabolismo , Mapas de Interação de Proteínas , Transdução de Sinais , Biologia Computacional , Regulação para Baixo , Redes Reguladoras de Genes , Humanos , Regulação para Cima
9.
Hum Biol ; 91(4): 257-277, 2020 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-32767896

RESUMO

The Fujian Tanka people are officially classified as a southern Han ethnic group, whereas they have customs similar to Daic and Austronesion people. Whether they originated in Han or Daic people, there is no consensus. Three hypotheses have been proposed to explain the origin of this group: (1) the Han Chinese origin, (2) the ancient Daic origin, (3) and the admixture between Daic and Han. This study addressed this issue by analyzing the paternal Y chromosome and maternal mtDNA variation of 62 Fujian Tanka and 25 neighboring Han in Fujian. The southern East Asian predominant haplogroups (e.g., Y-chromosome O1a1a-P203 and O1b1a1a-M95, and mtDNA F2a, M7c1, and F1a1) had relatively high frequencies in Tanka. The interpopulation comparison revealed that the Tanka have a closer affinity with Daic populations than with Han Chinese in paternal lineages but are closely clustered with southern Han populations such as Hakka and Chaoshanese in maternal lineages. Network and haplotype-sharing analyses also support the admixture hypothesis. The Fujian Tanka mainly originate from the ancient indigenous Daic people and have only limited gene flows from Han Chinese populations. Notably, the divergence time inferred by the Tanka-specific haplotypes indicates that the formation of Fujian Tanka was a least 1033.8-1050.6 years before present (the early Northern Song dynasty), indicating that they are an indigenous population, not late Daic migrants from southwestern China.


Assuntos
Cromossomos Humanos Y/genética , DNA Mitocondrial/genética , Genética Populacional/métodos , Grupo com Ancestrais do Continente Asiático/genética , China/etnologia , DNA Mitocondrial/história , Grupos Étnicos/genética , Feminino , Testes Genéticos/métodos , Haplótipos/genética , História Antiga , Humanos , Masculino , Polimorfismo de Nucleotídeo Único/genética
10.
J Craniofac Surg ; 2020 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-32657985

RESUMO

BACKGROUND: Gene alterations are very vital when it comes to the molecular pathogenesis of glioma. In this study, there was the design of the probable candidate genes in the glioma. METHODS: Gene Expression Omnibus (GEO) database data sets of glioma tissue were retrieved and the differentially expressed genes (DEGs) from the individual microarray were merged. The following were performed: Gene Ontology; enrichment analysis; Kyoto Encyclopedia of Genes and Genomes (KEGG); pathway analysis; protein-protein interaction networks analysis. RESULTS: The following were selected: 4 GEO data sets that included 370 high-grade glioma samples as well as 169 low-grade glioma samples. Identification of a total of 174 DEGs was done. Out of the identified DEGs, 82 were upregulated and 92 were downregulated genes. According to the Gene Ontology analysis, the primary biologic focus of DEGs included passive transmembrane transporter activity, regulation of channel activity, as well as the revelation that the biologic roles of DEGs aimed primarily on regulating channel activity, as well as the monovalent inorganic cation transmembrane transporter activity. The most significant pathway in KEGG analysis was PI3K-AKT signaling pathway. Some of the significant hub genes as per the protein-protein interaction network analysis included CDC20, NDC80, DLGAP5, CENPF, CENPE, ASPM, TPX2, TOP2A, RRM2, and PRC1. CONCLUSION: From this study, it is evidenced that the use of integrated bioinformatics analyses in screening for pathways and DEGs in glioma can help us understand the clinical significance of understanding glioma, the molecular mechanism that underlies the development of glioma, as well as the provision of an effective target to treat glioma.

11.
BMC Cancer ; 20(1): 94, 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32013960

RESUMO

BACKGROUND: Lymphovascular invasion (LVI) is a vital risk factor for prognosis across cancers. We aimed to develop a scoring system for stratifying LVI risk in patients with breast cancer. METHODS: A total of 301 consecutive patients (mean age, 49.8 ± 11.0 years; range, 29-86 years) with breast cancer confirmed by pathological reports were retrospectively evaluated at the authors' institution between June 2015 and October 2018. All patients underwent contrast-enhanced Magnetic Resonance Imaging (MRI) examinations before surgery. MRI findings and histopathologic characteristics of tumors were collected for analysis. Breast LVI was confirmed by postoperative pathology. We used a stepwise logistic regression to select variables and two cut-points were determined to create a three-tier risk-stratification scoring system. The patients were classified as having low, moderate and high probability of LVI. The area under the receiver operating characteristic curve (AUC) was used to evaluate the discrimination ability of the scoring system. RESULTS: Tumor margins, lobulation sign, diffusion-weighted imaging appearance, MRI-reported axillary lymph node metastasis, time to signal intensity curve pattern, and HER-2 were selected as predictors for LVI in the point-based scoring system. Patients were considered at low risk if the score was < 3.5, moderate risk if the score was 3.5 to 6.0, and high risk if the score was ≥6.0. LVI risk was segmented from 0 to 100.0% and was positively associated with an increase in risk scores. The AUC of the scoring system was 0.824 (95% confidence interval [CI]: 0.776--0.872). CONCLUSION: This study shows that a simple and reliable score-based risk-stratification system can be practically used in stratifying the risk of LVI in breast cancer.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Imagem de Difusão por Ressonância Magnética/métodos , Metástase Linfática/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Feminino , Humanos , Modelos Logísticos , Pessoa de Meia-Idade , Invasividade Neoplásica , Estudos Retrospectivos
12.
Sci Total Environ ; 715: 136258, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32007868

RESUMO

Ground-based multi-axis differential optical absorption spectroscopy (MAX-DOAS) observations were performed from 27 December 2018 to 16 January 2019 in Changshou, one of subdistricts of Chongqing, China. Primary atmospheric pollutant in Changshou during wintertime was PM2.5, whose contribution averaged about 70.15% ± 9.5% of PM10. The ratio of PM2.5/PM10 decreased when PM2.5 pollution became worse, and it should attribute to biomass burning and the contribution of hygroscopic growth and enhanced heterogeneous chemistry under high relative humidity condition. Moreover, nitrogen dioxide (NO2), formaldehyde (HCHO) and glyoxal (CHOCHO) vertical profiles during the campaign period were retrieved separately. TROPOMI HCHO vertical column densities (VCDs) and MAX-DOAS HCHO VCDs were correlated well (R = 0.93). In order to identify the sources of volatile organic compound (VOC) in Changshou, the ratio of CHOCHO to HCHO (RGF) in five different layers were estimated. The estimated daily averaged RGF were 0.0205 ± 0.0077, 0.0727 ± 0.0286, 0.0864 ± 0.0296, 0.0770 ± 0.0275 and 0.0746 ± 0.0263 in 0-100 m, 100-200 m, 300-400 m, 500-600 m and 700-800 m layers, respectively. The estimated RGF will increase when biomass burnings were dominated. Using NO2 as a tracer of anthropogenic emissions, we found the RGF values gradually decrease with the increase of NO2 levels. RGF values in 0-100 m layer and all the other upper layers are 0.015-0.025 and 0.06-0.14, and that means the dominant sources of VOCs in 0-100 m layer and all the other upper layers are biogenic emission and anthropogenic emission (especially biomass burning), respectively. In addition, we found that RGF has site dependence which is in compliance with several previous studies.

13.
Front Oncol ; 10: 583053, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33520699

RESUMO

Background: Deregulated purine metabolism is critical for fast-growing tumor cells by providing nucleotide building blocks and cofactors. Importantly, purine antimetabolites belong to the earliest developed anticancer drugs and are still prescribed in clinics today. However, these antimetabolites can inhibit non-tumor cells and cause undesired side effects. As liver has the highest concentration of purines, it makes liver cancer a good model to study important nodes of dysregulated purine metabolism for better patient selection and precisive cancer treatment. Methods: By using a training dataset from TCGA, we investigated the differentially expressed genes (DEG) of purine metabolism pathway (hsa00230) in hepatocellular carcinoma (HCC) and determined their clinical correlations to patient survival. A prognosis model was established by Lasso-penalized Cox regression analysis, and then validated through multiple examinations including Cox regression analysis, stratified analysis, and nomogram using another ICGC test dataset. We next treated HCC cells using chemical drugs of the key enzymes in vitro to determine targetable candidates in HCC. Results: The DEG analysis found 43 up-regulated and 2 down-regulated genes in the purine metabolism pathway. Among them, 10 were markedly associated with HCC patient survival. A prognostic correlation model including five genes (PPAT, DCK, ATIC, IMPDH1, RRM2) was established and then validated using the ICGC test dataset. Multivariate Cox regression analysis found that both prognostic risk model (HR = 4.703 or 3.977) and TNM stage (HR = 2.303 or 2.957) independently predicted HCC patient survival in the two datasets respectively. The up-regulations of the five genes were further validated by comparing between 10 pairs of HCC tissues and neighboring non-tumor tissues. In vitro cellular experiments further confirmed that inhibition of IMPDH1 significantly repressed HCC cell proliferation. Conclusion: In summary, this study suggests that purine metabolism is deregulated in HCC. The prognostic gene correlation model based on the five purine metabolic genes may be useful in predicting HCC prognosis and patient selection. Moreover, the deregulated genes are targetable by specific inhibitors.

14.
Light Sci Appl ; 8: 100, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31754427

RESUMO

Abundances of a range of air pollutants can be inferred from satellite UV-Vis spectroscopy measurements by using the unique absorption signatures of gas species. Here, we implemented several spectral fitting methods to retrieve tropospheric NO2, SO2, and HCHO from the ozone monitoring instrument (OMI), with radiative simulations providing necessary information on the interactions of scattered solar light within the atmosphere. We analyzed the spatial distribution and temporal trends of satellite-observed air pollutants over eastern China during 2005-2017, especially in heavily polluted regions. We found significant decreasing trends in NO2 and SO2 since 2011 over most regions, despite varying temporal features and turning points. In contrast, an overall increasing trend was identified for tropospheric HCHO over these regions in recent years. Furthermore, generalized additive models were implemented to understand the driving forces of air quality trends in China and assess the effectiveness of emission controls. Our results indicated that although meteorological parameters, such as wind, water vapor, solar radiation and temperature, mainly dominated the day-to-day and seasonal fluctuations in air pollutants, anthropogenic emissions played a unique role in the long-term variation in the ambient concentrations of NO2, SO2, and HCHO in the past 13 years. Generally, recent declines in NO2 and SO2 could be attributed to emission reductions due to effective air quality policies, and the opposite trends in HCHO may urge the need to control anthropogenic volatile organic compound (VOC) emissions.

15.
Opt Express ; 27(16): A1225-A1240, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31510516

RESUMO

We present the trend and seasonal variability of stratospheric NO2 column for the first time over the polluted atmosphere at Hefei, China, retrieved using Fourier transform infrared spectroscopy (FTIR) between 2015 and 2018. The FTIR observed stratospheric NO2 columns over Hefei show a peak in June and reach a minimum in January. The mean stratospheric NO2 column concentration in June is (3.49 ± 0.25) × 1015 molecules*cm-2, and is 39.20% ± 8.95% higher than that in January with a mean value of (2.51 ± 0.21) × 1015 molecules*cm-2. We find a negative trend of (-0.34 ± 0.05) %/yr in the FTIR observations of stratospheric NO2 column. The FTIR data are compared to the satellite OMI observations to assess the new data set quality and also applied to evaluate the GEOS-Chem model simulations. We find in general the OMI observations and GEOS-Chem model results are in good agreement with the coincident FTIR data, and they all show similar seasonal cycles with strong correlation coefficients of 0.84-0.86. The annual average OMI minus FTIR difference is (1.48 ± 5.33) × 1014 molecules*cm-2 (4.82% ± 17.37%), and average GEOS-Chem minus FTIR difference is (2.36 ± 2.33) × 1014 molecules*cm -2 (7.66% ± 7.49%). Their maximum differences occur in April and May with mean differences of 12-16%. We also found negative trends in the stratospheric NO2 column over Hefei for 2015-2018 with both OMI observations (-0.91 ± 0.09%/yr) and GEOS-Chem model results (-0.31 ± 0.05%/yr), demonstrating some consistency among them.

16.
Cancer Cell ; 36(2): 139-155.e10, 2019 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-31327655

RESUMO

The mechanisms that enable immune evasion at metastatic sites are poorly understood. We show that the Polycomb Repressor Complex 1 (PRC1) drives colonization of the bones and visceral organs in double-negative prostate cancer (DNPC). In vivo genetic screening identifies CCL2 as the top prometastatic gene induced by PRC1. CCL2 governs self-renewal and induces the recruitment of M2-like tumor-associated macrophages and regulatory T cells, thus coordinating metastasis initiation with immune suppression and neoangiogenesis. A catalytic inhibitor of PRC1 cooperates with immune checkpoint therapy to reverse these processes and suppress metastasis in genetically engineered mouse transplantation models of DNPC. These results reveal that PRC1 coordinates stemness with immune evasion and neoangiogenesis and point to the potential clinical utility of targeting PRC1 in DNPC.


Assuntos
Adenocarcinoma/metabolismo , Movimento Celular , Autorrenovação Celular , Quimiocina CCL2/metabolismo , Células-Tronco Neoplásicas/metabolismo , Complexo Repressor Polycomb 1/metabolismo , Neoplasias da Próstata/metabolismo , Evasão Tumoral , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/imunologia , Adenocarcinoma/secundário , Animais , Antineoplásicos Imunológicos/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Movimento Celular/efeitos dos fármacos , Autorrenovação Celular/efeitos dos fármacos , Quimiocina CCL2/genética , Inibidores Enzimáticos/farmacologia , Regulação Neoplásica da Expressão Gênica , Humanos , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Macrófagos/imunologia , Macrófagos/metabolismo , Masculino , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos NOD , Camundongos Knockout , Camundongos Nus , Camundongos SCID , Metástase Neoplásica , Células-Tronco Neoplásicas/imunologia , Células-Tronco Neoplásicas/patologia , Células PC-3 , Complexo Repressor Polycomb 1/antagonistas & inibidores , Complexo Repressor Polycomb 1/genética , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/imunologia , Neoplasias da Próstata/patologia , Receptores Androgênicos/deficiência , Receptores Androgênicos/genética , Receptores CCR4/genética , Receptores CCR4/metabolismo , Transdução de Sinais , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Evasão Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
17.
Nat Cell Biol ; 21(4): 534, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30842593

RESUMO

In the version of this Article originally published the same blot was inadvertently presented as both p-Rb and Cyclin A in Fig. 2a. This blot corresponds to the p-Rb panel, as can be seen in the unprocessed version of these blots in Supplementary Fig. 9. The corrected version of the panel is shown below, together with a completely uncropped image of both blots. In addition, in the 'Viral transduction' section of the Methods, the pLKO.1 plasmids encoding short hairpin RNAs targeting human Rnd1 were incorrectly listed as clones TRCN0000018338 and TRCN0000039977. The correct clone numbers are TRCN0000047434 and TRCN0000047435.

18.
Elife ; 82019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30924768

RESUMO

While genomic sequencing routinely identifies oncogenic alterations for the majority of cancers, many tumors harbor no discernable driver lesion. Here, we describe the exceptional molecular phenotype of a genomically quiet kidney tumor, clear cell papillary renal cell carcinoma (CCPAP). In spite of a largely wild-type nuclear genome, CCPAP tumors exhibit severe depletion of mitochondrial DNA (mtDNA) and RNA and high levels of oxidative stress, reflecting a shift away from respiratory metabolism. Moreover, CCPAP tumors exhibit a distinct metabolic phenotype uniquely characterized by accumulation of the sugar alcohol sorbitol. Immunohistochemical staining of primary CCPAP tumor specimens recapitulates both the depletion of mtDNA-encoded proteins and a lipid-depleted metabolic phenotype, suggesting that the cytoplasmic clarity in CCPAP is primarily related to the presence of glycogen. These results argue for non-genetic profiling as a tool for the study of cancers of unknown driver.


Assuntos
Carcinoma de Células Renais/patologia , Respiração Celular , Neoplasias Renais/patologia , Aerobiose , Histocitoquímica , Humanos , Imuno-Histoquímica , Redes e Vias Metabólicas , Oxirredução
19.
Nat Med ; 25(2): 284-291, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30559419

RESUMO

Activating BRAF mutants and fusions signal as RAS-independent constitutively active dimers with the exception of BRAF V600 mutant alleles which can function as active monomers1. Current RAF inhibitors are monomer selective, they potently inhibit BRAF V600 monomers but their inhibition of RAF dimers is limited by induction of negative cooperativity when bound to one site in the dimer1-3. Moreover, acquired resistance to these drugs is usually due to molecular lesions that cause V600 mutants to dimerize4-8. We show here that PLX8394, a new RAF inhibitor9, inhibits ERK signaling by specifically disrupting BRAF-containing dimers, including BRAF homodimers and BRAF-CRAF heterodimers, but not CRAF homodimers or ARAF-containing dimers. Differences in the amino acid residues in the amino (N)-terminal portion of the kinase domain of RAF isoforms are responsible for this differential vulnerability. As a BRAF-specific dimer breaker, PLX8394 selectively inhibits ERK signaling in tumors driven by dimeric BRAF mutants, including BRAF fusions and splice variants as well as BRAF V600 monomers, but spares RAF function in normal cells in which CRAF homodimers can drive signaling. Our work suggests that drugs with these properties will be safe and useful for treating tumors driven by activating BRAF mutants or fusions.


Assuntos
Compostos Heterocíclicos com 2 Anéis/farmacologia , Mutação/genética , Multimerização Proteica , Proteínas Proto-Oncogênicas B-raf/genética , Transdução de Sinais , Sulfonamidas/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Humanos , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas B-raf/metabolismo
20.
Sci Rep ; 7(1): 17368, 2017 12 12.
Artigo em Inglês | MEDLINE | ID: mdl-29234099

RESUMO

Recently, atmospheric ozone pollution has demonstrated an aggravating tendency in China. To date, most research about atmospheric ozone has been confined near the surface, and an understanding of the vertical ozone structure is limited. During the 2016 G20 conference, strict emission control measures were implemented in Hangzhou, a megacity in the Yangtze River Delta, and its surrounding regions. Here, we monitored the vertical profiles of ozone concentration and aerosol extinction coefficients in the lower troposphere using an ozone lidar, in addition to the vertical column densities (VCDs) of ozone and its precursors in the troposphere through satellite-based remote sensing. The ozone concentrations reached a peak near the top of the boundary layer. During the control period, the aerosol extinction coefficients in the lower lidar layer decreased significantly; however, the ozone concentration fluctuated frequently with two pollution episodes and one clean episode. The sensitivity of ozone production was mostly within VOC-limited or transition regimes, but entered a NOx-limited regime due to a substantial decline of NOx during the clean episode. Temporary measures took no immediate effect on ozone pollution in the boundary layer; instead, meteorological conditions like air mass sources and solar radiation intensities dominated the variations in the ozone concentration.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...