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1.
Environ Pollut ; 291: 118094, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34517175

RESUMO

Indoor air quality ((IAQ) in classrooms was associated with the daily exposure of school-age children who are particularly vulnerable to air pollutants exposure, while few data exist to evaluate classroom indoor air quality nationwide in China. The subsample of the CIEHS 2018 study was performed in 66 classrooms of 22 primary schools nationwide in China. Temperature, relative humidity, PM2.5, PM10, CO2, CO, formaldehyde concentrations, bacteria and fungi were detected in all classrooms by using the instruments that meet the specified accuracy. The ratios of indoor to outdoor (I/O) of PM2.5 were calculated in each classroom to identify whether the indoor environment the pollutants comes from outdoors. The indoor PM2.5, PM10, CO, HCHO, bacteria and fungi GM concentration are 47.40 µg/m3, 72.91 µg/m3, 0.37 mg/m3, 0.02 mg/m3, 347.51 CFU/m3 and 362.76 CFU/m3, respectively. We observed that there were 66.5%, 52.6%, 22.4%, 1.8%, and 9.6% of the classrooms that exceeded the guideline values of PM2.5, PM10, CO2, HCHO, and bacteria, respectively. It should be attention that all of the classroom's PM2.5 concentrations in Shijiazhuang and Nanning, PM10 concentrations in Nanning, CO2 concentration in Lanzhou were exceeded the suggested values. Bacteria contamination in Shijiazhuang's classrooms is also serious. All classroom CO concentrations meet the requirement. The results indicated that classroom indoor PM2.5 was significantly positively correlated with indoor PM10 and CO2, while was negative correlated with temperature, CO, and fungi. Our results suggest that indoor air pollution in classrooms was a severe problem in Chinese primary schools. It is necessary to strengthen ventilation in the classroom to improve indoor air quality. What's more, a healthy learning environment should be created for primary school students.

2.
Biomed Res Int ; 2021: 5473959, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34485514

RESUMO

Background: The hypercoagulable status, which forms a vicious cycle with hematogenous metastasis, is a common systemic alteration in cancers. As modeling is a key approach in research, a model which is suitable for studying how the hypercoagulable status promotes hematogenous metastasis in breast cancer is urgently needed. Methods: Based on the tumor-bearing period (TBP) and postoperative incubation period (PIP), 4T1-breast cancer models were constructed to evaluate coagulation and tumor burden to generate multiple linear regression-based lung metastasis prediction formula. Platelets and 4T1 cells were cocultured for 30 min or 24 h in vitro to evaluate the early and late phases of their crosstalk, and then the physical characteristics (concentration and size) and procoagulant activity of the coculture supernatants were assayed. Results: The multiple linear regression model was constructed as log10 (photon number) = 0.147 TBP + 0.14 PIP + 3.303 (TBP ≤ 25 and PIP ≤ 17) to predict lung metastasis. Coculture of platelets and 4T1 cells contributed to the release of extracellular vesicles (EVs) and the development of the hypercoagulable status. Conclusions: In vivo and in vitro hypercoagulable status models were developed to explore the mechanism of hypercoagulable status which is characterized by platelet activation and promotes hematogenous metastasis in breast cancer.


Assuntos
Neoplasias da Mama/sangue , Neoplasias da Mama/patologia , Neoplasias Hematológicas/sangue , Neoplasias Hematológicas/patologia , Trombofilia/sangue , Trombofilia/patologia , Animais , Linhagem Celular Tumoral , Modelos Animais de Doenças , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Modelos Teóricos , Metástase Neoplásica , Ativação Plaquetária
3.
Aging (Albany NY) ; 13(16): 20836-20852, 2021 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-34461608

RESUMO

Heparanase (HPSE), an endoglycosidase that cleaves heparan sulfate, regulates a variety of biological processes that promote tumor progression. In this study, we analyzed the correlation between HPSE expression and prognosis in cancer patients, using multiple databases (Oncomine, TIMER, PrognoScan, GEPIA, Kaplan-Meier plotter, miner v4.1, DAVID). HPSE expression was significantly increased in bladder, breast, lung, and stomach cancer compared to matched normal tissues. The increased HPSE expression correlated with poor prognosis and increased immune infiltration levels of B cells, CD8+ and CD4+ T cells, macrophages, neutrophils and dendritic cells in bladder and breast cancer. In breast cancer, the high HPSE expression was associated with basal-like subtypes, younger age (0-40), advanced Scarff-Bloom-Richardson grade, Nottingham Prognostic Index and p53 mutation status. In addition, using a mouse model of breast cancer, our data showed that HPSE upregulated IL-10 expression and promoted macrophage M2 polarization and T cell exhaustion. Together, our data provide a novel immunological perspective on the mechanisms underlying breast cancer progression, and indicate that HPSE may serve as a biomarker for immune infiltration and prognosis in breast cancer.

4.
Bioresour Technol ; 341: 125824, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34450443

RESUMO

To recover resource from waste activated sludge (WAS) is of great significance. This study proposed a promising way, i.e., stepwise alkaline treatment coupled with ammonia stripping, to remarkably enhance short-chain fatty acids (SCFAs) production from WAS anaerobic digestion. The maximal production of SCFAs, with the value of 323 mg COD/g volatile suspended solid, was obtained with first initial pH = 10 adjustment followed by second initial pH = 10 adjustment on third day coupled with ammonia stripping. Mechanistic studies showed that solubilization of both extracellular polymeric substances and cells could be accelerated by stepwise initial pH = 10 adjustment. However, without ammonia stripping, the activities of either acidogens or methanogens could be inhibited by free ammonia formed under alkaline conditions; positively, anaerobes related to SCFAs production were enriched with ammonia stripping. Moreover, the proposed strategy can simultaneously achieve nitrogen and carbon recovery, providing some solutions for the carbon-neutral operation of wastewater treatment plants.


Assuntos
Amônia , Esgotos , Ácidos Graxos Voláteis , Fermentação , Concentração de Íons de Hidrogênio
5.
Environ Res ; 202: 111731, 2021 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-34297935

RESUMO

BACKGROUND: Significant efforts have been directed toward addressing the adverse health effects of particulate matter, while few data exist to evaluate indoor exposure nationwide in China. OBJECTIVES: This study aimed to investigate dwellings particulate matter levels in the twelve cities in China and provide large data support for policymakers to accelerate the legislative process. METHODS: The current study was based on the CIEHS 2018 study and conducted in 12 cities of China. A total of 2128 air samples were collected from 610 residential households during the summer and winter. Both PM10 and PM2.5 were detected with a light-scattering dust meter in both the living room and bedroom. The Wilcoxon rank-sum test was performed to evaluate the correlations between PM2.5 and PM10 concentrations and both sampling season and site. Ratios of the living room to bedroom were calculated to evaluate the particulate matter variation between rooms. Hierarchical clustering was used to probe the question of whether the concentration varies between cities throughout China. RESULTS: The geometric means of the PM2.5 in living rooms and bedrooms were 39.80 and 36.55 µg/m3 in the summer, and 70.97 and 67.99 µg/m3 in the winter, respectively. In the summer, approximately 70 % of indoor dwelling PM2.5 exceeded the limit of 25 µg/m3, and for PM10 approximately 60 % of dwellings demonstrated levels higher than 50 µg/m3; the corresponding values were over 90 % and 80 % in winter, respectively. In Shijiazhuang, Lanzhou, Luoyang and Qingdao, the geometric means of the PM2.5 concentrations were observed to be 1.5 to 4.3 times higher during winter than during summer; similar concentrations in summer and winter were observed in Harbin, Wuxi, and Shenzhen, while the PM2.5 concentrations in Panjin were approximately 1.5 times higher in summer than in winter. There was no significant difference in particulate matter concentrations between the living rooms and bedrooms. Scatter plots showed that cities with low GDP and a small population had higher concentrations, while Shenzhen, which has a higher GDP and a large permanent population, had a relatively low concentration of particulate matter. CONCLUSIONS: Our results suggest that indoor air pollution is a severe problem in China. It is necessary to continue monitoring indoor air quality to observe the changing trend under the tremendous effort of the Chinese government.

6.
J Cogn Psychother ; 2021 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-34285137

RESUMO

Although negative life events are a risk factor for developing depression, cognitive control can help maintain one's mental health. However, whether thought-control ability (TCA) can alleviate the adverse effects of negative life events on depression is unclear. Therefore, two studies were conducted to test if it does, by having participant's complete measures of negative life events, TCA, and depression. Study 1, which included 140 healthy young adults, showed TCA mediated the relationship between negative life events and depressive symptoms, and that TCA also moderated the relationship between negative life events and depressive symptoms. Study 2 recruited patients with major depressive disorder (MDD) to test whether the findings could be generalized to individuals with MDD. Study 2 found TCA also mediated the relationship between negative life events and symptoms of MDD. Suggesting that improving the ability to control negative thoughts in daily life help maintain mental health and prevent depressive symptoms.

7.
Talanta ; 232: 122182, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34074380

RESUMO

Lanthanide nanoprobes have attracted extensive attention for applications in cellular imaging and biological sensing. Herein, water-dispersible europium (III)-based (Eu(III)-based) nanoprobes were prepared by reversible addition-fragmentation chain transfer (RAFT) polymerization-induced self-assembly (PISA) of hydrophobic monomers (Eu(III)-containing monomer and methyl methacrylate (MMA)) using hydrophilic macro-chain transfer agent poly(PEGMA)-CTA. The resulted poly(PMEu) nanoprobes showed spherical in shape in good monodispersity with average diameters of around 210 nm. The poly(PMEu) nanoprobles excellent aqueous dispersity, high aqueous stability and good luminescence properties with quantum yields of 37.21% and fluorescence lifetime of 312.4 µs. Moreover, the poly(PMEu) nanoprobes exhibited good cellular biocompatibility with cell viabilities of 88.2% and high fluorescence intensity for in vitro cellular imaging. The present approach provides a facile strategy for fabrication of luminescent Eu(III)-based nanoprobes with great potential applications for biological imaging.


Assuntos
Európio , Nanopartículas , Polimerização , Polímeros , Água
8.
Aging (Albany NY) ; 13(9): 12929-12954, 2021 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-33952716

RESUMO

Liver hepatocellular carcinoma (LIHC) remains one of the most common causes of cancer death. Prior research suggested that the PPM1G gene is involved in LIHC. To explore the role of PPM1G in LIHC, we used several online databases. Expression profiling was performed via the Gene Expression Profiling Interactive Analysis (GEPIA), Hepatocellular Carcinoma Database (HCCDB), Oncomine and Human Protein Atlas (HPA) platforms. Mutation profiles were investigated via cBio Cancer Genomics Portal (cBioPortal). Survival analysis was performed via the Kaplan-Meier (KM) plotter and International Cancer Genome Consortium (ICGC) platforms. The biological function of PPM1G was analyzed via the Enrichr database. The influence of PPM1G expression in the tumor immune microenvironment was assessed via Tumor Immune Estimation Resource (TIMER). PPM1G expression was upregulated in various tumors, including LIHC. Overexpression of PPM1G was associated with poor prognosis in LIHC. PPM1G expression might be regulated by promoter methylation, copy number variations (CNVs) and kinases and correlate with immune infiltration. The gene ontology (GO) terms associated with high PPM1G expression were mRNA splicing and the cell cycle. The results suggest that PPM1G is correlated with the prognosis of LIHC patients and associated with the tumor immune microenvironment in LIHC.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/mortalidade , Neoplasias Hepáticas/mortalidade , Proteína Fosfatase 2C/genética , Microambiente Tumoral/imunologia , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/imunologia , Variações do Número de Cópias de DNA , Metilação de DNA , Análise Mutacional de DNA , Conjuntos de Dados como Assunto , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica/imunologia , Redes Reguladoras de Genes/imunologia , Humanos , Estimativa de Kaplan-Meier , Fígado/imunologia , Fígado/patologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/imunologia , Mutação , Prognóstico , Regiões Promotoras Genéticas/genética , Microambiente Tumoral/genética , Regulação para Cima/imunologia
9.
Indoor Air ; 31(5): 1391-1401, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33876854

RESUMO

Household fine particulate matter (PM2.5 ) pollution greatly impacts residents' health. To explore the current national situation of household PM2.5 pollution in China, a study was conducted based on literature published from 1998 to 2018. After extracting data from the literature in conformity with the requirements, the nationwide household-weighted mean concentration of household PM2.5 (HPL) was calculated. Subgroup analyses of spatial, geographic, and temporal differences were also done. The estimated overall HPL in China was 132.2 ± 117.7 µg/m3 . HPL in the rural area (164.3 ± 104.5 µg/m3 ) was higher than that in the urban area (123.9 ± 122.3 µg/m3 ). For HPLs of indoor sampling sites, the kitchen was the highest, followed by the bedroom and living room. There were significant differences of geographic distributions. The HPLs in the South were higher than the North in four seasons. The inhaled dose of household PM2.5 among school-age children differed from provinces with the highest dose up to 5.9 µg/(kg·d). Countermeasures should be carried out to reduce indoor pollution and safeguard health urgently.


Assuntos
Poluentes Atmosféricos , Poluição do Ar em Ambientes Fechados/análise , Exposição Ambiental , Poluição do Ar em Ambientes Fechados/estatística & dados numéricos , Criança , China , Culinária , Monitoramento Ambiental , Características da Família , Humanos , Material Particulado , População Rural , Estações do Ano
10.
Bioresour Technol ; 331: 125035, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33820702

RESUMO

The plastic products have large consumption over last decades, resulting in a serious microplastics (MPs) pollution. Specially, the main removal way of MPs from wastewater is to transfer MPs from liquid to solid phase, leading to its enrichment in waste activated sludge (WAS). Anaerobic digestion has been served as the most potential technique to achieve both resource recovery and sludge reduction, herein this review provides current information on occurrence, effect, and fate of MPs in anaerobic digestion of WAS. The effects of MPs on WAS anaerobic digestion are greatly related to forms, particles sizes, contents, compositions and leachates of MPs. Also, the presence of MPs not only can change the effects of other pollutants on anaerobic digestion of WAS, but also can affect the fates of them. Besides, the future perspectives focused on the fate, effect and final removal of MPs during WAS anaerobic digestion process are outlined.


Assuntos
Microplásticos , Esgotos , Anaerobiose , Plásticos , Eliminação de Resíduos Líquidos , Águas Residuárias
11.
J Mater Chem B ; 9(9): 2266-2274, 2021 03 11.
Artigo em Inglês | MEDLINE | ID: mdl-33605286

RESUMO

A hybrid self-healing hydrogel (PM hydrogel), based on polyvinyl alcohol (PVA) and chemically exfoliated molybdenum disulfide (ce-MoS2) nanosheets, was prepared by a simple freeze-thaw method. Due to the excellent photothermal conversion properties of ce-MoS2 nanosheets, the PM hydrogel self-repaired rapidly under near infrared (NIR) light irradiation for only 3 min with a high healing efficiency of 91.8 ± 3.3%. The PVA content, ce-MoS2 nanosheet loading and light irradiation time played important roles in the self-healing performance. Additionally, the PM hydrogel also revealed good self-healing properties with a healing efficiency of 60.6 ± 3.6% after the cut surfaces were separated for 24 h. The present approach provides an effective strategy for fabricating fast light-triggered hydrogen-bond based self-healing systems. The as-prepared hybrid PM hydrogel has great potential as a soft biomaterial for long-term applications due to its biocompatibility and self-healing capability.


Assuntos
Dissulfetos/química , Hidrogéis/química , Luz , Molibdênio/química , Nanoestruturas/química , Álcool de Polivinil/química , Ligação de Hidrogênio , Fenômenos Mecânicos
12.
Ying Yong Sheng Tai Xue Bao ; 32(1): 317-325, 2021 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-33477240

RESUMO

In order to evaluate the effects of polystyrene microplastics (PS-MPs) on the growth, physiology, and biochemical characteristics of submerged plants, we exposed a typical submerged plant, Hydrilla verticillata, to a series of concentrations (i.e. 0, 5, 10, 30, 50, 100 mg·L-1) of 3 µm polystyrene microplastics (PS-MPs) and measured parameters including height, biomass, chlorophyll content, antioxidant enzyme activity, photosynthetic fluorescence. The results showed that the height of H. Verticillata significantly decreased at the high PS-MP concentrations (50 to 100 mg·L-1), while the fresh weight significantly increased at the low PS-MP concentration (5 mg·L-1). The fresh weight of H. verticillata gradually decreased with the increasing PS-MP concentration but the dry weight did not change. The total amount of chlorophyll, chlorophyll a, and chlorophyll a/b significantly decreased with the increases of the PS-MP concentrations, while the chlorophyll b did not change. PS-MPs affected the antioxidant enzyme activities of H. verticillata. The activities of superoxide dismutase (SOD), catalase (CAT) and peroxidase (POD) were first increased and then decreased with the increasing PS-MP concentration. The chlorophyll fluorescence parameters (Fo, Fm, Fv/Fm) decreased with the increasing concentration of PS-MP and the 1-Qp-Lss value (reflective of the closing of PSⅡ reaction center) was increased under the stable state, probably due to the inhibited PSⅡ reaction center. The overall intensity of fluorescence imaging of H. verticillata decreased with the increasing concentration of PS-MPs. When the PS-MP concentration was lower than 10 mg·L-1, the photosynthetic activity of the leaves was normal. In contrast, when the PS-MP concentration was higher than 30 mg·L-1, it caused significant adverse effects on leaves, including weaker photosynthetic intensity and the presence of yellow or withered leaves. Our results suggested that H. verticillata could tolerate PS-MP pollution but its growth and photosynthesis would be inhibited at high concentrations (>30 mg·L-1). Our results provided basic information to better understand the eco-physiological effects of PS-MPs in the freshwater environment.


Assuntos
Hydrocharitaceae , Microplásticos , Clorofila , Clorofila A , Plásticos , Poliestirenos/toxicidade
13.
J Surg Res ; 258: 389-404, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33109405

RESUMO

BACKGROUND: Intestinal ischemia-reperfusion (I/R) injury is a common clinical event with high mortality, but its mechanism is elusive. Although long noncoding RNAs (lncRNAs) have recently emerged as critical molecules in I/R damage in other organs, the changes in their expression and potential roles in intestinal I/R remain unclear. METHODS: The expression profiles of both lncRNAs and mRNAs in mouse intestinal mucosa after intestinal I/R were explored by a microarray approach, and their biological functions were elucidated by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Then, some lncRNAs were further verified by qRT-PCR. Based on the coding-noncoding gene coexpression (CNC) network analyses, the role of lncRNA AK089510 in intestinal I/R-induced intestinal mucosa apoptosis was investigated by knockdown assay in vitro. RESULTS: A total of 3602 aberrantly expressed lncRNAs (1503 upregulated and 2099 downregulated) and 3158 mRNAs (1528 upregulated and 1630 downregulated) were identified. The dysregulated transcripts were enriched in the lipid metabolic process, apoptotic process, reactive oxygen species metabolic process, MAPK, TNF, ErbB, mTOR, and FoxO signaling pathways, and so on. The overexpression of lncRNA AK089510 was validated by qRT-PCR, and the CNC analysis revealed its target mRNAs. AK089510-siRNA reduced Casp6 and Casp7 expression and suppressed intestinal epithelial cell apoptosis after oxygen-glucose deprivation treatment. CONCLUSIONS: Our study revealed the lncRNA and mRNA expression patterns in mouse intestinal mucosa after intestinal I/R and predicted their potential functions and pathways. We identified AK089510 as a novel lncRNA involved in the apoptosis of intestinal mucosa, advancing our understanding of the molecular mechanisms of intestinal I/R injury.


Assuntos
Mucosa Intestinal/metabolismo , RNA Longo não Codificante/metabolismo , RNA Mensageiro/metabolismo , Traumatismo por Reperfusão/metabolismo , Animais , Células Cultivadas , Mucosa Intestinal/irrigação sanguínea , Masculino , Camundongos Endogâmicos C57BL , Análise em Microsséries , Traumatismo por Reperfusão/etiologia
14.
J Colloid Interface Sci ; 586: 601-612, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33189325

RESUMO

The fabrication of flexible electronic sensors with self-healing capability is of great importance for the applications in wearable devices and skin-like electronics. Herein, a molybdenum disulfide (MoS2) nanosheets-based hydrogel (Gel-PEG-MoS2, GPM hydrogel), with near infrared (NIR) light-induced self-healing property, was first reported as a flexible sensor. Only a small amount of MoS2 nanosheets (0.04 wt‰) could impart the hydrogel with fast self-healing property under NIR irradiation in 90 s. The healing efficiencies increased with the increasing of MoS2 loadings. Moreover, the GPM hydrogel exhibited both contact and noncontact sensing properties based on its deformation-dependent and light-sensitive conductivity, showing potential application as mechanical sensor and light-activated switches. By employing the versatile MoS2 nanosheets, the hydrogel exhibited both fast self-healing ability and mechanical/light sensing capability. Therefore, the MoS2-based hydrogel provides a two-pronged approach for construction of self-healing flexible electronics.

15.
Cell Death Dis ; 11(10): 895, 2020 10 22.
Artigo em Inglês | MEDLINE | ID: mdl-33093445

RESUMO

Accumulating evidence indicates that hepatocellular carcinoma (HCC) tumorigenesis, recurrence, metastasis, and therapeutic resistance are strongly associated with liver cancer stem cells (CSCs), a rare subpopulation of highly tumorigenic cells with self-renewal capacity and differentiation potential. Previous studies identified B cell leukemia/lymphoma-11b (BCL11B) as a novel tumor suppressor with impressive capacity to restrain CSC traits. However, the implications of BCL11B in HCC remain unclear. In this study, we found that low BCL11B expression was an independent indicator for shorter overall survival (OS) and time to recurrence (TTR) for HCC patients with surgical resection. In vitro and in vivo experiments confirmed BCL11B as a tumor suppressor in HCC with inhibitory effects on proliferation, cell cycle progression, apoptosis, and mobility. Furthermore, BCL11B could suppress CSC traits, as evidenced by dramatically decreased tumor spheroid formation, self-renewal potential and drug resistance. A Cignal Finder Array and dual-luciferase activity reporter assays revealed that BCL11B could activate the transcription of P73 via an E2F1-dependent manner. Thus, we concluded that BCL11B is a strong suppressor of retaining CSC traits in HCC. Ectopic expression of BCL11B might be a promising strategy for anti-HCC treatment with the potential to cure HBV-related HCC regardless of P53 mutation status.


Assuntos
Carcinogênese/efeitos dos fármacos , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Células-Tronco Neoplásicas/efeitos dos fármacos , Proteínas Repressoras/fisiologia , Proteína Supressora de Tumor p53/fisiologia , Proteínas Supressoras de Tumor/fisiologia , Animais , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Carcinogênese/genética , Carcinogênese/metabolismo , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sinergismo Farmacológico , Regulação Neoplásica da Expressão Gênica , Genes Supressores de Tumor , Células Hep G2 , Humanos , Masculino , Camundongos , Camundongos Nus , Proteínas Repressoras/farmacologia , Transdução de Sinais , Proteína Tumoral p73/fisiologia , Proteína Supressora de Tumor p53/genética , Proteínas Supressoras de Tumor/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto
16.
Int J Oncol ; 57(4): 890-904, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32945393

RESUMO

Triple­negative breast cancer (TNBC), which is characterized by inherently aggressive behavior and lack of recognized molecular targets for therapy, poses a serious threat to women's health worldwide. However, targeted treatments have yet to be made available. A crosstalk between tumor cells and platelets (PLT) contributing to growth, angiogenesis and metastasis has been reported in numerous cancers. Heparanase (Hpa), the only mammalian endoglycosidase that cleaves heparan sulfate, has been demonstrated to contribute to the growth, angiogenesis and metastasis of numerous cancers. Hypoxia affects the growth, angiogenesis and metastasis of nearly all solid tumors, and the ability of Hpa to promote invasion is enhanced in hypoxia. However, whether Hpa can strengthen the crosstalk between tumor cells and PLT, and whether enhancing the biological function of Hpa in TNBC promotes malignant progression, have yet to be fully elucidated. The present study, based on bioinformatics analysis and experimental studies in vivo and in vitro, demonstrated that Hpa enhanced the crosstalk between TNBC cells and PLT to increase the supply of oxygen and nutrients, while also conferring tolerance of TNBC cells to oxygen and nutrient shortage, both of which are important for overcoming the stress of hypoxia and nutritional deprivation in the tumor microenvironment, thereby promoting malignant progression, including growth, angiogenesis and metastasis in TNBC. In addition, the hypoxia­inducible factor­1a (HIF-1a)/vascular endothelial growth factor­a (VEGF- a)/phosphorylated protein kinase B (p-)Akt axis may be the key pathway involved in the effects of Hpa on the biological processes mentioned above. Therefore, improving local hypoxia, anti­Hpa treatment and inhibiting PLT activation may improve the prognosis of TNBC.

17.
Clin Chim Acta ; 511: 67-74, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32979338

RESUMO

AIMS: The present study aimed to determine the prognostic significance of soluble Programmed Death-ligand 1 (sPD-L1) in hepatocellular carcinoma (HCC) patients undergoing transcatheter arterial chemoembolization (TACE). METHODS: We treated 114 HCC patients with TACE from 2012 to 2013 and determined their sPD-L1 levels by enzyme-linked immunosorbent assay. We evaluated prognosis according to mRESIST criteria and analyzed prognostic values by Cox regression and Kaplan-Meier analysis. We further evaluated correlations between sPD-L1 level and inflammatory status, as well as immunosuppressive environment. RESULTS: sPD-L1 levels were significantly increased in patients who developed HCC progression (P = 0.002) and death (P < 0.001). Patients with higher pre-treatment sPD-L1 levels had a significantly shorter time to progression (10.50 vs. 18.25 months, P = 0.001) and decreased overall survival (16.50 vs. 28.50 months, P = 0.003). Importantly, sPD-L1 levels positively correlated with SII (r = 0.284, P = 0.002), sIL-2R (r = 0.239, P = 0.010), IL-10 (r = 0.283, P = 0.002), HBV-DNA loads (r = 0.229, P = 0.014), and CRP (r = 0.237, P = 0.011). Moreover, high sPD-L1 levels had increased numbers of Treg cells (FOXP3+; P = 0.026), Macrophage cells (CD68+; P = 0.014), and M2-Macrophage cells (CD163+; P = 0.026) CONCLUSIONS: sPD-L1 level is a prognostic indicator of poor outcomes after TACE. High sPD-L1 might reflect increased immune activation in an immunosuppressive environment that hindered anti-tumor response activity.


Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Antígeno B7-H1 , Biomarcadores Tumorais , Carcinoma Hepatocelular/terapia , Humanos , Imunossupressão , Neoplasias Hepáticas/terapia , Prognóstico
18.
BMC Genet ; 21(1): 63, 2020 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-32552710

RESUMO

BACKGROUND: The disease gene of fragile X syndrome, FMR1 gene, encodes fragile X mental retardation protein (FMRP). The alternative splicing (AS) of FMR1 can affect the structure and function of FMRP. However, the biological functions of alternatively spliced isoforms remain elusive. In a previous study, we identified a new 140bp exon from the intron 9 of human FMR1 gene. In this study, we further examined the biological functions of this new exon and its underlying signaling pathways. RESULTS: qRT-PCR results showed that this novel exon is commonly expressed in the peripheral blood of normal individuals. Comparative genomics showed that sequences paralogous to the 140 bp sequence only exist in the genomes of primates. To explore the biological functions of the new transcript, we constructed recombinant eukaryotic expression vectors and lentiviral overexpression vectors. Results showed that the spliced transcript encoded a truncated protein which was expressed mainly in the cell nucleus. Additionally, several genes, including the BEX1 gene involved in mGluR-LTP or mGluR-LTD signaling pathways were significantly influenced when the truncated FMRP was overexpressed. CONCLUSIONS: our work identified a new exon from amid intron 9 of human FMR1 gene with wide expression in normal healthy individuals, which emphasizes the notion that the AS of FMR1 gene is complex and may in a large part account for the multiple functions of FMRP.


Assuntos
Processamento Alternativo , Éxons , Proteína do X Frágil de Retardo Mental/genética , Células HEK293 , Humanos , Íntrons
19.
J Nat Prod ; 83(4): 1217-1228, 2020 04 24.
Artigo em Inglês | MEDLINE | ID: mdl-32159343

RESUMO

Environmental toxicant- and oxidant-induced [e.g., cigarette smoke (CS)] respiratory oxidative stress and inflammatory response play a vital role in the onset and progression of COPD. The nuclear factor erythroid 2-related factor 2 (Nrf2) represents an important mechanism for regulating intracellular oxidative stress and inflammatory response and is a promising target for developing agents against COPD. Herein, a bioactivity-guided purification of goldenberry (whole fruits of Physalis peruviana L.) led to the isolation of a novel and potent Nrf2 activator 4ß-hydroxywithanolide E (4ß-HWE). Our study indicated that (i) 4ß-HWE activated the Nrf2-mediated defensive response through interrupting Nrf2-Keap1 protein-protein interaction (PPI) via modification of Cys151 and Cys288 cysteine residues in Keap1 and accordingly suppressing the ubiquitination of Nrf2. (ii) 4ß-HWE enhanced intracellular antioxidant capacity and inhibited oxidative stress in normal human lung epithelial Beas-2B cells and wild-type AB zebrafish. (iii) 4ß-HWE blocked LPS-stimulated inflammatory response and inhibited LPS-stimulated NF-κB activation in RAW 264.7 murine macrophages. (iv) 4ß-HWE effectively suppressed oxidative stress and inflammatory response in a CS-induced mice model of pulmonary injury. Collectively, these results display the feasibility of using 4ß-HWE to prevent or alleviate the pathological progression of COPD and suggest that 4ß-HWE is a candidate or a leading molecule against COPD.


Assuntos
Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Pulmão/patologia , Fator 2 Relacionado a NF-E2/metabolismo , Physalis/química , Vitanolídeos/farmacologia , Animais , Antioxidantes/farmacologia , Células Epiteliais/efeitos dos fármacos , Frutas , Humanos , Proteína 1 Associada a ECH Semelhante a Kelch/química , Camundongos , Estrutura Molecular , Fator 2 Relacionado a NF-E2/química , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Fumaça , Tabaco , Vitanolídeos/química , Vitanolídeos/isolamento & purificação
20.
Gene ; 731: 144359, 2020 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-31935509

RESUMO

FMRP is an RNA-binding protein, loss of which causes fragile X syndrome (FXS). FMRP has several isoforms resulted from alternative splicing (AS) of fragile X mental retardation 1 (FMR1) gene, but their biological functions are still poorly understood. In the analysis of alternatively spliced FMR1 transcripts in the blood cells from a patient with FXS-like phenotypes (normal CGG repeats and no mutation in coding sequence of FMR1), we identified three novel FMR1 transcripts that include a previously unidentified microexon (46 bp), terming the exon 9a. This microexon exists widely in unaffected individuals, inclusion of which introduces an in-frame termination codon. To address whether these exon 9a-containing transcripts could produce protein by evading nonsense-mediated decay (NMD), Western blot was used to analysis blood cell lysate from unaffected individuals and a 34 kDa protein that consistent in size with the molecular weight of the predicted truncated protein produced from mRNA with this microexon was found. Meanwhile, treatment of peripheral blood mononuclear cells with an inhibitor of NMD (Cycloheximide) did not result in significant increase in exon 9a-containing transcripts. Using confocal immunofluorescence, we found the truncated protein displayed both nuclear and cytoplasmic localization in HEK293T and HeLa cells due to lacking C-terminal domains including KH2, NES, and RGG, while the full-length FMRP protein mainly localized in the cytoplasm. Therefore, we hypothesize that the inclusion of this microexon to generate exon 9a-containing transcripts may regulate the normal functionality of FMRP, and the dysregulation of normal FMRP due to increased exon 9a-containing alternatively spliced transcripts in that patient may be associated with the manifestation of FXS phenotype.


Assuntos
Proteína do X Frágil de Retardo Mental/genética , Proteína do X Frágil de Retardo Mental/metabolismo , Splicing de RNA/fisiologia , Adulto , Processamento Alternativo/fisiologia , Estudos de Casos e Controles , Núcleo Celular/metabolismo , Citoplasma/metabolismo , Éxons/genética , Síndrome do Cromossomo X Frágil/genética , Síndrome do Cromossomo X Frágil/metabolismo , Síndrome do Cromossomo X Frágil/patologia , Células HEK293 , Células HeLa , Humanos , Masculino , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Distribuição Tecidual
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