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2.
Int J Biol Macromol ; 134: 1002-1012, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31063785

RESUMO

The combination of controlled release technology and targeted drug delivery has become a promising strategy for cancer therapy. In this study, cell-nanoparticle hybrid vector was constructed using mesenchymal stem cells as the targeting cellular carrier and biotinylated chitosan polymer nanoparticles as the drug depot. Drug-loaded nanoparticles (hydrodynamic size =377.0 ±â€¯14.6 nm and zeta potential = 9.6 ±â€¯1.9 mV) were prepared by encapsulating hydrophobic model drug curcumin into biotinylated chitosan polymer. The biotin-modified nanoparticles were anchored on biotinylated mesenchymal stem cells surface by biotin-avidin binding, achieving an upload of 54.73 ±â€¯3.95 pg/cell. The anchorage of nanoparticles on mesenchymal stem cells had no effect on their viability and homing property. Biotin-avidin binding lasted over 48 h, which could be sufficient for cell-directed tumor-tropic delivery. The in vitro and in vivo anti-tumor results advocate that cell-nanoparticle hybrid vector could prove beneficial in pulmonary melanoma metastasis therapy.


Assuntos
Quitosana , Curcumina/administração & dosagem , Portadores de Fármacos , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/metabolismo , Nanopartículas , Animais , Biotina , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Quitosana/química , Curcumina/química , Modelos Animais de Doenças , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Imunofluorescência , Masculino , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/efeitos dos fármacos , Camundongos , Nanopartículas/química , Nanopartículas/ultraestrutura , Neoplasias/terapia , Polímeros , Carga Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
3.
Light Sci Appl ; 8: 47, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31123586

RESUMO

The newly launched Fengyun-3D (FY-3D) satellite carried a wide-field auroral imager (WAI) that was developed by Changchun Institute of Optics, Fine Mechanics and Physics, Chinese Academy of Sciences (CIOMP), which will provide a large field of view (FOV), high spatial resolution, and broadband ultraviolet images of the aurora and the ionosphere by imaging the N2 LBH bands of emissions. The WAI consists of two identical cameras, each with an FOV of 68° in the along-track direction and 10° in the cross-track direction. The two cameras are tilted relative to each other to cover a fan-shaped field of size 130° × 10°. Each camera consists of an unobstructed four-mirror anastigmatic optical system, a BaF2 filter, and a photon-counting imaging detector. The spatial resolution of WAI is ~10 km at the nadir point at a reference height of 110 km above the Earth's surface. The sensitivity is >0.01 counts s-1 Rayleigh-1 pixel-1 (140-180 nm) for both cameras, which is sufficient for mapping the boundaries and the fine structures of the auroral oval during storms/substorms. Based on the tests and calibrations that were conducted prior to launch, the data processing algorithm includes photon signal decoding, geometric distortion correction, photometric correction, flat-field correction, line-of-sight projection and correction, and normalization between the two cameras. Preliminarily processed images are compared with DMSP SSUSI images. The agreement between the images that were captured by two instruments demonstrates that the WAI and the data processing algorithm operate normally and can provide high-quality scientific data for future studies on auroral dynamics.

4.
Oncol Res ; 27(7): 849-858, 2019 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-30982492

RESUMO

Over the past decade, natural compounds have been proven to be effective against many human diseases, including cancers. Triptolide (TPL), a diterpenoid triepoxide from the Chinese herb Tripterygium wilfordii Hook F, has exhibited attractive cytotoxic activity on several cancer cells. An increasing number of studies have emphasized the antitumor effects of TPL on non-small cell lung cancer (NSCLC). Here we mainly focused on the key molecular signaling pathways that lead to the inhibitory effects of TPL on human NSCLC, such as mitogen-activated protein kinases (MAPKs) modulation, inhibition of NF-κB activation, suppression of miRNA expression, etc. In addition, the effect of TIG on immune response in cancer patients is summarized for improved immune modulation utilization. However, the clinical use of TPL is often limited by its severe toxicity and water insolubility. Future clinical trials and drug delivery strategies that will evaluate the security and validate the underlying tumor-killing properties of TPL in human NSCLC are also to be discussed.

5.
Sci Rep ; 9(1): 6220, 2019 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-30996271

RESUMO

With the rapid growth of the aging population, exploring the biological basis of aging and related molecular mechanisms has become an important topic in modern scientific research. Aging can cause multiple organ function attenuations, leading to the occurrence and development of various age-related metabolic, nervous system, and cardiovascular diseases. In addition, aging is closely related to the occurrence and development of tumors. Although a number of studies have used various mouse models to study aging, further research is needed to associate mouse and human aging at the molecular level. In this paper, we systematically assessed the relationship between human and mouse aging by comparing multi-tissue age-related gene expression sets. We compared 18 human and mouse tissues, and found 9 significantly correlated tissue pairs. Functional analysis also revealed some terms related to aging in human and mouse. And we performed a crosswise comparison of homologous age-related genes with 18 tissues in human and mouse respectively, and found that human Brain_Cortex was significantly correlated with Brain_Hippocampus, which was also found in mouse. In addition, we focused on comparing four brain-related tissues in human and mouse, and found a gene-GFAP-related to aging in both human and mouse.

6.
Sci China Life Sci ; 62(5): 661-667, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30900164

RESUMO

The lack of refined spatial detail on bird distribution in China has hindered further research due to the large geographic unit (provincial level) in existing national bird distribution data. Based on multi-source bird distribution data, we built a more spatially detailed distribution database for every bird species (1,371 species) in China, covering 2,908 counties. The sources on bird distribution are grouped into six categories: Handbooks, Literature; Fauna, Avifauna; Paper; Citizen Science data by ornithologists or birders; GPS tracing; and Website data. The database contains the following records: taxonomy, distribution data, suspicious species information, and data sources. Our database recorded 835 species (61%) appearing outside the distribution range previously known. The use of provincial boundaries as the smallest geographical unit has created misleading distribution results due to geographic aggregation for most species. The new database was built based on increased observational frequency and individuals observed in previously undetected areas particularly in Western China and towards higher altitudes and latitudes. They coincided with the discovery of the range expansion of some waterfowls into Xinjiang. The dataset provides a new base for Chinese and international ornithology studies, especially for those requiring more detailed distribution information for many taxa and large-scale regional research.

7.
Brain Behav Immun ; 79: 114-124, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30682501

RESUMO

Antidepressant-like effects of metabotropic glutamate receptor 5 (mGluR5) have been verified by specific antagonists or whole body knock-out (KO) mice. Previous experiments indicate that blocking mGluR5 exerts antidepressant-like effects through neuronal mechanisms, like modulating NMDA receptor activity or 5-HT system. Here we found that transplanting bone marrow from mGluR5 KO mice to WT mice could also show antidepressant-like effects, which were confirmed by sucrose preference test and tail suspension test. Furthermore, mGluR5 deficiency dramatically inhibits cytokines release from bone marrow cells, such as IL-1ß, TNF-α and IL-6, alleviating proinflammatory responses in LPS-induced depression model. In addition, inhibited cytokines could decrease the activation of brain endothelial cells in ERK-dependent manner. These data provide the evidence that blocking mGluR5 could improve depression through inhibiting peripheral immune responses, confirming the causal relationship between peripheral immune phenotype and brain behavior.

8.
Chin Med J (Engl) ; 132(1): 51-62, 2019 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-30628959

RESUMO

BACKGROUND: Some porous materials have been developed to enhance biologic fusion of the implants to bone in spine fusion surgeries. However, there are several inherent limitations. In this study, a novel biomedical porous tantalum was applied to in vitro and in vivo experiments to test its biocompatibility and osteocompatibility. METHODS: Bone marrow-derived mesenchymal stem cells (BMSCs) were cultured on porous tantalum implant. Scanning electron microscope (SEM) and Cell Counting Kit-8 assay were used to evaluate the cell toxicity and biocompatibility. Twenty-four rabbits were performed discectomy only (control group), discectomy with autologous bone implanted (autograft group), and discectomy with porous tantalum implanted (tantalum group) at 3 levels: L3-L4, L4-L5, and L5-L6 in random order. All the 24 rabbits were randomly sacrificed at the different post-operative times (2, 4, 6, and 12 months; n = 6 at each time point). Histologic examination and micro-computed tomography scans were done to evaluate the fusion process. Comparison of fusion index scores between groups was analyzed using one-way analysis of variance. Other comparisons of numerical variables between groups were made by Student t test. RESULTS: All rabbits survived and recovered without any symptoms of nerve injury. Radiographic fusion index scores at 12 months post-operatively between autograft and tantalum groups showed no significant difference (2.89 ±â€Š0.32 vs. 2.83 ±â€Š0.38, F = 244.60, P = 0.709). Cell Counting Kit-8 assay showed no significant difference of absorbance values between the leaching liquor group and control group (1.25 ±â€Š0.06 vs. 1.23 ±â€Š0.04, t = -0.644, P = 0.545), which indicated the BMSC proliferation without toxicity. SEM images showed that these cells had irregular shapes with long spindles adhered to the surface of tantalum implant. No implant degradation, wear debris, or osteolysis was observed. Histologic results showed solid fusion in the porous tantalum and autologous bone implanted intervertebral spaces. CONCLUSION: This novel porous tantalum implant showed a good biocompatibility and osteocompatibility, which could be a valid biomaterial for interbody fusion cages.


Assuntos
Tantálio/química , Animais , Proliferação de Células/fisiologia , Discotomia , Vértebras Lombares/cirurgia , Microscopia Eletrônica de Varredura , Próteses e Implantes , Coelhos , Fusão Vertebral
9.
J Neuroinflammation ; 15(1): 146, 2018 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-29776443

RESUMO

Our knowledge of the pathophysiology about traumatic brain injury (TBI) is still limited. Neutrophils, as the most abundant leukocytes in circulation and the first-line transmigrated immune cells at the sites of injury, are highly involved in the initiation, development, and recovery of TBI. Nonetheless, our understanding about neutrophils in TBI is obsolete, and mounting evidences from recent studies have challenged the conventional views. This review summarizes what is known about the relationships between neutrophils and pathophysiology of TBI. In addition, discussions are made on the complex roles as well as the controversial views of neutrophils in TBI.


Assuntos
Lesões Encefálicas Traumáticas/patologia , Lesões Encefálicas Traumáticas/fisiopatologia , Neutrófilos/fisiologia , Animais , Humanos
10.
Front Genet ; 9: 12, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29441089

RESUMO

The 14-3-3 gene family members play key roles in various cellular processes. However, little is known about the numbers and roles of 14-3-3 genes in wheat. The aims of this study were to identify TaGF14 numbers in wheat by searching its whole genome through blast, to study the phylogenetic relationships with other plant species and to discuss the functions of TaGF14s. The results showed that common wheat harbored 20 TaGF14 genes, located on wheat chromosome groups 2, 3, 4, and 7. Out of them, eighteen TaGF14s are non-ε proteins, and two wheat TaGF14 genes, TaGF14i and TaGF14f, are ε proteins. Phylogenetic analysis indicated that these genes were divided into six clusters: cluster 1 (TaGF14d, TaGF14g, TaGF14j, TaGF14h, TaGF14c, and TaGF14n); cluster 2 (TaGF14k); cluster 3 (TaGF14b, TaGF14l, TaGF14m, and TaGF14s); cluster 4 (TaGF14a, TaGF14e, and TaGF14r); cluster 5 (TaGF14i and TaGF14f); and cluster 6 (TaGF14o, TaGF14p, TaGF14q, and TaGF14t). Tissue-specific gene expressions suggested that all TaGF14s were likely constitutively expressed, except two genes, i.e., TaGF14p and TaGF14f. And the highest amount of TaGF14 transcripts were observed in developing grains at 20 days post anthesis (DPA), especially for TaGF14j and TaGF14l. After drought stress, five genes, i.e., TaGF14c, TaGF14d, TaGF14g, TaGF14h, and TaGF14j, were up-regulated expression under drought stress for both 1 and 6 h, suggesting these genes played vital role in combating against drought stress. However, all the TaGF14s were down-regulated expression under heat stress for both 1 and 6 h, indicating TaGF14s may be negatively associated with heat stress by reducing the expression to combat heat stress or through other pathways. These results suggested that cluster 1, e.g., TaGF14j, may participate in the whole wheat developing stages, e.g., grain-filling (starch biosynthesis) and may also participate in combating against drought stress. Subsequently, a homolog of TaGF14j, TaGF14-JM22, were cloned by RACE and used to validate its function. Immunoblotting results showed that TaGF14-JM22 protein, closely related to TaGF14d, TaGF14g, and TaGF14j, can interact with AGP-L, SSI, SSII, SBEIIa, and SBEIIb in developing grains, suggesting that TaGF14s located on group 4 may be involved in starch biosynthesis. Therefore, it is possible to develop starch-rich wheat cultivars by modifying TaGF14s.

11.
Oncotarget ; 9(1): 1444-1460, 2018 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-29416705

RESUMO

Circular RNAs, as recently discovered new endogenous non-coding RNAs, are important gene modulators with critical roles in tumor initiation and malignant progression. With the development of RNA sequencing and microarray technologies, numerous of functional circRNAs have been identified in cancerous tissues and cell lines. Mechanistically, circRNAs function as miRNA sponges, miRNA reservoirs or parental gene expression regulators. In this review, we discuss the properties and functions of circRNAs and their clinical implication as promising biomarkers for cancer research. Moreover, some emerging fields, such as exosome-loaded and immune response-associated circRNAs, are also discussed, suggesting novel insights into the carcinogenesis and therapy associated with these molecules.

12.
Int J Surg ; 51: 174-179, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29360612

RESUMO

BACKGROUND: Anterior temporal lobectomy (ATL) is the standard surgical treatment for temporal lobe epilepsy (TLE), but patients may suffer from recurrent seizures post-surgery. Invasive electrical monitoring plays a critical role in precisely identifying the epileptic foci. This study aimed to evaluate and compare the benefits of long-term invasive electroencephalography (EEG) monitoring and two-stage surgery with the classical approach to examine their effect on post-surgical brain function and complications. MATERIALS AND METHODS: Patients with TLE (N = 198) who underwent epilepsy surgery were retrospectively evaluated. Diagnosis of TLE was confirmed based on clinical grounds (semiology), EEG findings, and magnetic resonance imaging (MRI). Long-term invasive video EEG was performed; epileptiform discharges were recorded. Patients underwent either classical ATL or modified two-step surgery with electrodes implantation. Histopathological examination was performed. The patients were followed up at 1, 3, and 5 years after surgery. RESULTS: Twenty-three and 175 patients underwent classical ATL and two-stage surgery, respectively. On histopathological examination, inflammation, hippocampal sclerosis, and cortical dysplasia were found to be the leading pathological causes of epileptic foci in both groups. MRI results were not consistent with the pathological findings. Grade II and III Engel scores were more frequent in the ATL group compared to two-stage surgery during follow-up. No postoperative complications were reported in two-stage surgery during follow-up, but one patient had mild hemiplegia in the ATL group. CONCLUSIONS: Preoperative invasive monitoring with long-term EEG helps locate the epileptic foci precisely. Postsurgical complications are rare compared to classical ATL, with better prognosis and seizure freedom after surgery.


Assuntos
Lobectomia Temporal Anterior/efeitos adversos , Epilepsia do Lobo Temporal/cirurgia , Complicações Pós-Operatórias/terapia , Convulsões/terapia , Adolescente , Adulto , Eletrodos , Eletroencefalografia , Epilepsia do Lobo Temporal/diagnóstico por imagem , Epilepsia do Lobo Temporal/fisiopatologia , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/fisiopatologia , Estudos Retrospectivos , Convulsões/fisiopatologia
13.
Genes (Basel) ; 9(1)2018 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-29300342

RESUMO

There is increasing evidence for the contribution of synuclein alpha (SNCA) to the etiology of neurological disorders, such as Parkinson's disease (PD). However, little is known about the detailed role of SNCA in human cancers, especially lung cancers. Here, we evaluated the effects of SNCA on the occurrence and prognosis of lung adenocarcinoma (ADC). Comprehensive bioinformatics analyses of data obtained from the Oncomine platform, the human protein atlas (HPA) project and the cancer cell line encyclopedia (CCLE) demonstrated that SNCA expression was significantly reduced in both ADC tissues and cancer cells. The results of relevant clinical studies indicated that down-regulation of SNCA was statistically correlated with shorter overall survival time and post-progression survival time. Through analysis of datasets obtained from the Gene Expression Omnibus database, significant low levels of SNCA were identified in cisplatin-resistant ADC cells. Moreover, small interfering RNA (siRNA)-mediated knockdown of protein tyrosine kinase 7 (PTK7) elevated the expression of SNCA in the ADC cell lines H1299 and H2009. Our work demonstrates that low levels of SNCA are specifically found in ADC and that this gene may be a potential therapeutic target for this subset of lung cancers. Determination of the role of SNCA in ADC biology would give us some insightful information for further investigations.

14.
Water Sci Technol ; 76(9-10): 2313-2320, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29144289

RESUMO

A new circular microchannel device has been proposed for the removal of chromium(III) from aqueous waste solution by using kerosene as a diluent and (2-ethylhexyl) 2-ethylhexyl phosphonate as an extractant. The proposed device has several advantages such as a flexible and easily adaptable design, easy maintenance, and cheap setup without the requirement of microfabrication. To study the extraction efficiency and advantages of the circular microchannel device in the removal of chromium(III), the effects of various operating conditions such as the inner diameter of the channel, the total flow velocity, the phase ratio, the initial pH of aqueous waste solution, the reaction temperature and the initial concentration of extractant on the extraction efficiency are investigated and the optimal process conditions are obtained. The results show that chromium(III) in aqueous waste solution can be effectively removed with (2-ethylhexyl) 2-ethylhexyl phosphonate in the circular microchannel. Under optimized conditions, an extraction efficiency of chromium(III) of more than 99% can be attained and the aqueous waste solution can be discharged directly, which can meet the Chinese national emission standards.


Assuntos
Cromo/isolamento & purificação , Extração Líquido-Líquido/métodos , Poluentes Químicos da Água/isolamento & purificação , Purificação da Água/métodos , Cromo/análise , Concentração de Íons de Hidrogênio , Querosene/análise , Extração Líquido-Líquido/instrumentação , Água , Poluentes Químicos da Água/análise , Purificação da Água/instrumentação
15.
Sci Rep ; 7(1): 9998, 2017 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-28855570

RESUMO

Both brain native inflammatory cells and infiltrated peripheral white blood cells (WBCs) are primary participants in the brain inflammatory damage post-TBI. Metabotropic glutamate receptor 5 (mGluR5) has been reported to regulate microglias and astrocytes to affect inflammation after TBI, but its effect on modulating infiltrated peripheral WBCs remains unclear. In a mouse moderate TBI model, we found that mGluR5 knockout (KO) significantly reduced neutrophil infiltration and inflammatory cytokine expression in the brain at 24 hours post TBI, which was accompanied by improved neurological dysfunction. Further investigation indicated that mGluR5 KO reduced the permeability of blood-brain barrier (BBB), the entrance for neutrophils to enter brain, and markedly decreased the mRNA levels of neutrophil-associated chemokines in brain tissue, including CXCL1, CXCL2, CCL2, CCL4 and CCL5. Using brain microvascular endothelial cells (BMECs), neutrophils and a BBB model in vitro, we confirmed the inhibitory effect of mGluR5 deficiency on neutrophil infiltration and demonstrated that blockade of protein kinase C (PKC) signaling was involved in it. These results provide insight into the role of mGluR5 in the regulation of inflammation in the acute phase of TBI, which may provide novel clues for TBI therapy.


Assuntos
Barreira Hematoencefálica/patologia , Lesões Encefálicas Traumáticas/patologia , Infiltração de Neutrófilos , Receptor de Glutamato Metabotrópico 5/metabolismo , Animais , Células Cultivadas , Citocinas/biossíntese , Modelos Animais de Doenças , Células Endoteliais/fisiologia , Camundongos , Camundongos Knockout , Receptor de Glutamato Metabotrópico 5/deficiência
17.
PLoS One ; 12(4): e0175977, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28414793

RESUMO

Radiotherapy is a powerful tool in the treatment of cancer that has the advantage of preserving normal tissues. However, tumor radioresistance currently remains a major impediment to effective RT. Thus, exploring effective radiation sensitizers is urgently needed. In this study, we have shown that diosmetin, the aglycone of the lavonoid glycoside from olive leaves, citrus fruits and some medicinal herbs, has a promising effect on radiotherapy sensitization. In our results, DIO could induce G1 phase arrest and thus enhance the radiosensitivity of radioresistant A549/IR lung cancer cells. Furthermore, DIO also restrains the IR-induced DNA damage repair by inhibiting the activated Akt signaling pathway. The combination of Akt inhibition (DIO, LY294002 or MK-2206) and radiation potently blocked A549/IR cancer cell proliferation. In summary, these observations suggest that the natural compound DIO could act as a potential drug for the treatment of radioresistant lung cancer cells.


Assuntos
Flavonoides/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Tolerância a Radiação/efeitos dos fármacos , Radiossensibilizantes/farmacologia , Transdução de Sinais/efeitos dos fármacos , Células A549 , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cromonas/farmacologia , Reparo do DNA/efeitos dos fármacos , Fase G1/efeitos dos fármacos , Compostos Heterocíclicos com 3 Anéis/farmacologia , Humanos , Morfolinas/farmacologia
18.
Sci Rep ; 7: 40735, 2017 01 27.
Artigo em Inglês | MEDLINE | ID: mdl-28128221

RESUMO

Due to complicated interactions in the atmospheric environment, quantifying the influence of individual meteorological factors on local PM2.5 concentration remains challenging. The Beijing-Tianjin-Hebei (short for Jing-Jin-Ji) region is infamous for its serious air pollution. To improve regional air quality, characteristics and meteorological driving forces for PM2.5 concentration should be better understood. This research examined seasonal variations of PM2.5 concentration within the Jing-Jin-Ji region and extracted meteorological factors strongly correlated with local PM2.5 concentration. Following this, a convergent cross mapping (CCM) method was employed to quantify the causality influence of individual meteorological factors on PM2.5 concentration. The results proved that the CCM method was more likely to detect mirage correlations and reveal quantitative influences of individual meteorological factors on PM2.5 concentration. For the Jing-Jin-Ji region, the higher PM2.5 concentration, the stronger influences meteorological factors exert on PM2.5 concentration. Furthermore, this research suggests that individual meteorological factors can influence local PM2.5 concentration indirectly by interacting with other meteorological factors. Due to the significant influence of local meteorology on PM2.5 concentration, more emphasis should be given on employing meteorological means for improving local air quality.

19.
Front Pharmacol ; 8: 960, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29354058

RESUMO

Resistance to temozolomide (TMZ), the standard chemotherapy agent for glioblastoma (GBM), poses a major clinical challenge to GBM prognosis. Understanding the mechanisms of TMZ resistance can help to identify novel drug targets and more effective therapies. Recent studies suggest that bioenergetic alterations of cancer cells play important roles in drug resistance. In our study, the altered metabolism of cancer cells was observed using a metabolic PCR array. We found that stearoyl-coenzyme A desaturase 1 (SCD1), a key rate-limiting enzyme for synthesis of monounsaturated fatty acids, was significantly upregulated in TMZ-resistant GBM cells compared to their parental counterparts. Overexpression of SCD1 promoted resistance to TMZ in parental GBM cells, whereas SCD1 downregulation by siRNA could re-sensitize TMZ-resistant cells in vitro. Combinational treatment of TMZ and an SCD1-specific inhibitor showed a combined inhibitory effect on TMZ-resistant glioma cells. We also observed that overexpression of SCD1 promoted Akt/GSK3ß/ß-catenin signaling, while silencing of SCD1 inhibited the signaling. The combination of an Akt activator with exogenous SCD1 or the combined inhibition of Akt and enforced expression of SCD1 resulted in the most significant changes of Akt signaling. Functionally, significantly lower viability and mobility rates were observed in TMZ-resistant cells when treated with Akt inhibitors and an SCD1 inhibitor simultaneously compared to when treated individually. In conclusion, our study identified SCD1 along with its functional pathway as a novel target in the development of TMZ resistance. SCD1 inhibition used alone or in combination with Akt inhibition could effectively overcome TMZ resistance in gliomas.

20.
Sci Total Environ ; 575: 956-962, 2017 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-27742060

RESUMO

Climate change mainly refers to long-term change in weather variables, and it has significant impact on sustainability and spread of infectious diseases. Among three leading infectious diseases in China, dysentery is exclusively sensitive to climate change. Previous researches on weather variables and dysentery mainly focus on determining correlation between dysentery incidence and weather variables. However, the contribution of each variable to dysentery incidence has been rarely clarified. Therefore, we chose a typical county in epidemic of dysentery as the study area. Based on data of dysentery incidence, weather variables (monthly mean temperature, precipitation, wind speed, relative humidity, absolute humidity, maximum temperature, and minimum temperature) and lagged analysis, we used principal component analysis (PCA) and classification and regression trees (CART) to examine the relationships between the incidence of dysentery and weather variables. Principal component analysis showed that temperature, precipitation, and humidity played a key role in determining transmission of dysentery. We further selected weather variables including minimum temperature, precipitation, and relative humidity based on results of PCA, and used CART to clarify contributions of these three weather variables to dysentery incidence. We found when minimum temperature was at a high level, the high incidence of dysentery occurred if relative humidity or precipitation was at a high level. We compared our results with other studies on dysentery incidence and meteorological factors in areas both in China and abroad, and good agreement has been achieved. Yet, some differences remain for three reasons: not identifying all key weather variables, climate condition difference caused by local factors, and human factors that also affect dysentery incidence. This study hopes to shed light on potential early warnings for dysentery transmission as climate change occurs, and provide a theoretical basis for the control and prevention of dysentery.


Assuntos
Disenteria/epidemiologia , Tempo (Meteorologia) , China/epidemiologia , Mudança Climática , Humanos , Umidade , Incidência , Temperatura Ambiente
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