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1.
Trends Mol Med ; 2020 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-32402849

RESUMO

The pathogenesis of autoimmune diseases (AIDs) is not only attributed to genetic susceptibilities but also environmental factors, among which, disturbed gut microbiota has attracted increasing attention. Compositional and functional changes of gut microbiota have been reported in various AIDs, and increasing evidence suggests that disturbed gut microbiota contributes to their immunopathogenesis. The accepted mechanisms include abnormal microbial translocation, molecular mimicry, and dysregulation of both local and systemic immunity. Studies have also suggested microbiota-based classification models and therapeutic interventions for patients with AIDs. Further in-depth mechanistic studies on microbiota-autoimmunity interplay in AIDs are urgently needed and underway to explore novel and precise diagnostic biomarkers and develop disease and patient-tailored therapeutic strategies.

2.
Life Sci ; 253: 117572, 2020 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-32201276

RESUMO

AIMS: Liver fibrosis is a chronic liver disease characterized by hepatic stellate cell (HSC) activation. Peroxisome proliferator-activated receptor gamma (PPARγ) play an important role in HSC activation. This study aimed to investigate the role of PPARγ in the progression of human hepatic fibrosis and the mechanism by which microRNA-942 regulates HSC activation. METHODS: 70 chronic hepatitis B (CHB) patients liver tissues were used to assess PPARγ, α-SMA and miR-942 levels by immunoblot and real-time PCR. Human primary HSCs or LX2 cells were used to perform multiple molecular experiments based on the transfection of small interfering RNA (siRNA) or co-transfection of microRNA inhibitor. Site-directed mutagenesis and luciferase reporter assays were used to identify miR-942 targets. miR-942 expression and localization in hepatic fibrosis and co-localization between α-SMA were determined by fluorescence in situ hybridization (FISH). KEY FINDINGS: The mRNA expression of PPARγ was decreased in activated HSCs and CHB patients with liver fibrosis, which was negatively correlated with F stage and α-SMA. miR-942 negatively regulates PPARγ expression via targeting the PPARγ 3'UTR. Inhibiting PPARγ promoted TGFß1 induced HSC activation, and this effect was blocked after inhibiting the miR-942. Moreover, miR-942 was mainly expressed in fibrous septa and negatively correlated with PPARγ in liver fibrosis. SIGNIFICANCE: PPARγ targeting by miR-942 and decreasing HSC activation in human hepatic fibrosis. Hence, regulating PPARγ may be a promising therapeutic strategy for hepatic fibrosis.

3.
Artigo em Inglês | MEDLINE | ID: mdl-32062366

RESUMO

Albendazole (ABZ) is the first-line drug in treating echinococcosis, which is recommended by WHO. To address the poor bioavailability of albendazole, liposomal albendazole was formulated and is available in our hospital for many years. In this study, a sensitive, reliable and accurate UPLC-Q-TOF-MS method was developed and validated for the determination of albendazole and its metabolites, albendazole sulfoxide (ABZSO), albendazole sulfone (ABZSO2) and albendazole-2-aminosulfone (ABZSO2NH2) in naturally echinococcus granulosus (E. granulosus) infected sheep plasma and tissues with mebendazole (MBZ) as the internal standard (IS). Plasma and tissues samples were prepared by protein precipitation method. The separation was performed on an ACQUITY UPLC® BEH C18 column (2.1 × 50 mm, 1.7 µm) with a gradient mobile phase consisting of methanol and water containing 0.1% formic acid at 0.4 mL/min. The detection was performed on a quadrupole time-of-flight (Q-TOF) high-resolution mass spectrometer using positive electrospray ionization (ESI) source with a chromatographic run time of 6.0 min. The detection was operated using target ions of [M + H]+ at m/z 266.096 for ABZ, m/z 282.091 for ABZSO, m/z 298.086 for ABZSO2, m/z 240.081 for ABZSO2NH2 and m/z 296.104 for IS in selective ion mode, respectively. This method was validated in terms of selectivity, linearity, precision, accuracy, recovery, matrix effect, dilution effect, carryover effects, stability, calibration curve and LLOQ. All validation parameter results were within the acceptable range described in guideline for bioanalytical method validation. This method has been successfully applied to the pharmacokinetic study following single and multiple oral dose of 10 mg/kg liposomal albendazole, and tissue distribution study following multiple oral dose of 10 mg/kg, with emulsion albendazole as the reference preparation. The results in the article will provide valuable information for use in clinical applications of liposomal albendazole and also be beneficial for further development of liposomal albendazole in future studies.


Assuntos
Albendazol/sangue , Albendazol/farmacocinética , Cromatografia Líquida de Alta Pressão/métodos , Equinococose/tratamento farmacológico , Doenças dos Ovinos/tratamento farmacológico , Albendazol/química , Albendazol/uso terapêutico , Animais , Equinococose/veterinária , Echinococcus granulosus , Modelos Lineares , Lipossomos , Espectrometria de Massas/métodos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Ovinos , Distribuição Tecidual
4.
Environ Sci Technol ; 54(5): 2869-2877, 2020 03 03.
Artigo em Inglês | MEDLINE | ID: mdl-31888327

RESUMO

Bisphenol S (BPS), an alternative for bisphenol A (BPA) that is present in thermal paper and numerous consumer products, has been linked to estrogenic, cytotoxic, genotoxic, neurotoxic, and immunotoxic responses. However, the mechanisms of BPS toxicity remain poorly understood. Here, following exposure to environmentally relevant concentrations ranging from 0.1 to 100 µg/L BPS, transcriptional changes evaluated by enriched gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Ingenuity Pathway Analysis (IPA) predicted cardiac disease and impairment of immune function in zebrafish at the embryo-to-larvae stage. Consistent with impacts predicted by transcriptional changes, significant sublethal impacts were observed ranging from reduced heart rate [8.7 ± 2.4% reductions at 100 µg/L BPS treatment; P < 0.05] to abnormal cardiac morphology [atrial/ventricle area significantly increased; 36.2 ± 9.6% at 100 µg/L BPS treatment; P < 0.05]. RNA-sequencing analysis results also indicated changes in nitric oxide synthetase (NOS2) and interleukin 12 (IL12) after BPS treatment, which was confirmed at the protein level. Increased expression of other cytokine genes was observed in larvae, suggesting inflammatory responses may be contributing to cardiac impairment by BPS. BPS caused cardiotoxicity, which temporally corresponded with inflammatory responses as predicted from RNA sequencing and confirmed at the protein and cellular levels of biological organization. Additional study is needed to find causal linkages between these responses.


Assuntos
Transcriptoma , Peixe-Zebra , Animais , Compostos Benzidrílicos , Cardiotoxicidade , Fenóis , Sulfonas
5.
Anal Chem ; 92(3): 2612-2619, 2020 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-31948230

RESUMO

RNA modification, such as N1-methyladenosine (m1A), affects the secondary structure of RNA and its ability to recognize specific reader proteins. Methods for detecting site-specific m1A are in demand. We report here a ligation-assisted differentiation approach for quantitative detection of m1A in mRNA with single-base resolution. The methyl group in m1A disrupts the Watson-Crick base pairing with uridine, resulting in a lower ligation efficiency of certain ligases and lower amounts of ligation products. Detection of the ligation products using quantitative real-time PCR provided site-specific evaluation of m1A. We first screened appropriate ligase and found that T3 DNA ligase offered the best discrimination between m1A and adenosine. We successfully detected and quantified m1A at position 1674 of bromodomain containing 2 (BRD2) mRNA from HEK293T cells. In lung carcinoma tissues, the level of m1A at position 1674 of BRD2 mRNA was significantly decreased compared to the tumor-adjacent normal tissues, suggesting that site-specific m1A may be involved in carcinogenesis.

6.
J Mater Chem B ; 8(5): 919-927, 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-31912848

RESUMO

Copper ions (Cu2+) and l-cysteine (l-Cys) in the human body always play critical roles in various physiological processes, while abnormal Cu2+ and l-Cys concentrations in the biological system lead to many diseases. In this manuscript, Si-doped carbon dots (Si-CDs) with near-infrared fluorescence were designed for the detection of Cu2+ and l-Cys through the fluorescence "on-off-on" mode. The carbon dots exhibited not only excellent optical merits including good stability against photobleaching and high chemical stability, but also superior biological compatibility. Interestingly, due to the abundant amino groups distributed on the surface of Si-CDs, they could bind to copper ions to form cupric amine complexes and then quench the fluorescence of Si-CDs due to an electron transfer process. In addition, upon the addition of l-Cys, the FL intensity of Si-CDs could be effectively recovered accompanied with complexation between Cu2+ and the functional groups in l-Cys, due to which Cu2+ was removed from the surface of Si-CDs. Notably, as far as we know, these are the first red-emitting carbon dots for copper ion and l-Cys assays in water samples and human plasma samples. Furthermore, this strategy was successfully applied to the determination of Cu2+ and l-Cys in living systems, demonstrating great practicability in biomedical applications.

7.
Neurobiol Dis ; 134: 104612, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31533065

RESUMO

Our understanding of mesial temporal lobe epilepsy (MTLE), one of the most common form of drug-resistant epilepsy in humans, is derived mainly from clinical, imaging, and physiological data from humans and animal models. High-throughput gene expression studies of human MTLE have the potential to uncover molecular changes underlying disease pathogenesis along with novel therapeutic targets. Using RNA- and small RNA-sequencing in parrallel, we explored differentially expressed genes in the hippocampus and cortex of MTLE patients who had undergone surgical resection and non-epileptic controls. We identified differentially expressed genes in the hippocampus of MTLE patients and differentially expressed small RNAs across both the cortex and hippocampus. We found significant enrichment for astrocytic and microglial genes among up-regulated genes, and down regulation of neuron specific genes in the hippocampus of MTLE patients. The transcriptome profile of the small RNAs reflected disease state more robustly than mRNAs, even across brain regions which show very little pathology. While mRNAs segregated predominately by brain region for MTLE and controls, small RNAs segregated by disease state. In particular, our data suggest that specific miRNAs (e.g., let-7b-3p and let-7c-3p) may be key regulators of multiple pathways related to MTLE pathology. Further, we report a strong association of other small RNA species with MTLE pathology. As such we have uncovered novel elements that may contribute to the establishment and progression of MTLE pathogenesis and that could be leveraged as therapeutic targets.

8.
IEEE Trans Vis Comput Graph ; 26(1): 906-916, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31478860

RESUMO

Combining data content with visual embellishments, infographics can effectively deliver messages in an engaging and memorable manner. Various authoring tools have been proposed to facilitate the creation of infographics. However, creating a professional infographic with these authoring tools is still not an easy task, requiring much time and design expertise. Therefore, these tools are generally not attractive to casual users, who are either unwilling to take time to learn the tools or lacking in proper design expertise to create a professional infographic. In this paper, we explore an alternative approach: to automatically generate infographics from natural language statements. We first conducted a preliminary study to explore the design space of infographics. Based on the preliminary study, we built a proof-of-concept system that automatically converts statements about simple proportion-related statistics to a set of infographics with pre-designed styles. Finally, we demonstrated the usability and usefulness of the system through sample results, exhibits, and expert reviews.

9.
J Autoimmun ; : 102360, 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31806420

RESUMO

OBJECTIVE: Gut dysbiosis has been reported implicated in ankylosing spondylitis (AS), a common chronic inflammatory disease mainly affects sacroiliac joints and spine. Utilizing deep sequencing on the feces of untreated AS patients, our study aimed at providing an in-depth understanding of AS gut microbiota. METHODS: We analyzed the fecal metagenome of 85 untreated AS patients and 62 healthy controls by metagenomic shotgun sequencing, and 23 post-treatment feces of those AS patients were collected for comparison. Comparative analyses among different cohorts including AS, rheumatoid arthritis and Behcet's disease were performed to uncover some common signatures related to inflammatory arthritis. Molecular mimicry of a microbial peptide was also demonstrated by ELISpot assay. RESULTS: We identified AS-enriched species including Bacteroides coprophilus, Parabacteroides distasonis, Eubacterium siraeum, Acidaminococcus fermentans and Prevotella copri. Pathway analysis revealed increased oxidative phosphorylation, lipopolysaccharide biosynthesis and glycosaminoglycan degradation in AS gut microbiota. Microbial signatures of AS gut selected by random forest model showed high distinguishing accuracy. Some common signatures related to autoimmunity, such as Bacteroides fragilis and type III secretion system (T3SS), were also found. Finally, in vitro experiments demonstrated an increased amount of IFN-γ producing cells triggered by a bacterial peptide of AS-enriched species, mimicking type II collagen. CONCLUSIONS: These findings collectively indicate that gut microbiota was perturbed in untreated AS patients with diagnostic potential, and some AS-enriched species might be triggers of autoimmunity by molecular mimicry. Additionally, different inflammatory arthritis shared some common microbial signatures.

10.
Front Oncol ; 9: 1108, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31781482

RESUMO

Acute myeloid leukemia (AML) is a myeloid malignancy characterized by the proliferation of abnormal and immature myeloid blasts in the bone marrow. Circular RNA (circRNA) is a novel class of long non-coding RNA with a stable circular conformation that regulates various biological processes. The aberrant expression of circRNA and its impact on AML progression has been reported by a number of studies. Despite recent advances in circRNA research, our understanding of the leukemogenic mechanism of circRNA remains very limited, and translating the current circRNA-related research into clinical practice is challenging. This review provides an update on the functional roles of and research progress on circRNAs in AML with an emphasis on mechanistic insights. The challenges and opportunities associated with circRNA-based diagonostic and therapeutic development in AML are also outlined.

11.
Math Biosci Eng ; 16(6): 6907-6922, 2019 07 29.
Artigo em Inglês | MEDLINE | ID: mdl-31698595

RESUMO

Recently, fully convolutional network (FCN) has been successfully used to locate spliced regions in synthesized images. However, all the existing FCN-based algorithms use real-valued FCN to process each channel separately. As a consequence, they fail to capture the inherent correlation between color channels and the integrity of three channels. So, in this paper, quaternion fully convolutional network (QFCN) is proposed to generalize FCN to quaternion domain by replacing real-valued conventional blocks in FCN with quaternion conventional blocks. In addition, a new color image splicing localization algorithm is proposed by combining QFCNs and superpixel (SP)-enhanced pairwise conditional random field (CRF). QFCNs consider three different versions (QFCN32, QFCN16, and QFCN8) with different up-sampling layers. The SP-enhanced pairwise CRF is used to refine the results of QFCNs. Experimental results on three publicly available datasets demonstrate that the proposed algorithm outperforms the existing algorithms including some conventional algorithms and some deep learning-based algorithms.

12.
Opt Lett ; 44(18): 4527-4530, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31517922

RESUMO

A twin-Fano resonator based on a Mach-Zehnder interferometer (MZI) is demonstrated on a silicon-on-insulator platform. A dual-microring resonator replaces one of the couplers of the MZI to achieve twin-Fano resonance, which originates from the interference and coupling of modes in a dual-microring resonator. The slope can be tuned in a wide range from -84.2 dB/nm to 91.0 dB/nm by metal heaters integrated on one arm of the MZI, and the resonant wavelength remains fixed when the slope changes. The "X-type" spectrum is shown by self-alignment, which means manual alignment to form the X-type line is unnecessary after tuning dual-microrings because the X-type line can be produced easily by the difference in two correlated spectra rather than two independent spectra. The measurement shows high wavelength resolution of 1 pm in the region of the slope of 127.4 dB/nm, which can be applied to wavelength monitoring with ultra-high resolution.

13.
J Clin Neurosci ; 69: 15-20, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31526678

RESUMO

Photosensitive is probably caused by multiple factors including gender, familiar, etc. We aim to study the clinical and EEG features of Chinese Han patients with photosensitivity. A total of 5482 consecutive patients with possible epilepsy from 3 center in China. Of the 73 patients with PPR to IPS, 48 were female. 69.9% patients were evoked by frequency ranged 8 Hz-25 Hz, with accompanying seizures in 13 patients. 6 of 9 patients with eyes closure sensitivity experienced epileptic seizures during IPS. We found some new features: 1) The patients with eyes closure sensitivity apt to experience electro-clinical seizures provoked by IPS; 2) Female epilepsy patients with PPR and ECS maybe difficult to be seizure free. Preventive measures for related seizures should be performed to the patients with generalized PPR, upper threshold evoking frequency, and eyes closure sensitivity when they received the IPS.


Assuntos
Epilepsia Reflexa/epidemiologia , Epilepsia Reflexa/etiologia , Estimulação Luminosa/efeitos adversos , Adolescente , Adulto , Grupo com Ancestrais do Continente Asiático , Criança , China/epidemiologia , Eletroencefalografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
14.
Chem Res Toxicol ; 32(10): 2078-2085, 2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31433169

RESUMO

Hexavalent chromium [Cr(VI)] compounds that are generated during industrial processes are widely recognized as highly toxic and carcinogenic. It has been reported that exposure to Cr(VI) can produce some chromium intermediates and reactive oxygen species (ROS), which causes DNA damages, genetic instability, and eventually leads to the elevated risk of various diseases including cancers. In recent years, it has been proposed that epigenetic-based mechanisms may involve in the toxic heavy metals-induced cytotoxicity and mutagenicity besides the genetic-based mechanisms. However, whether Cr(VI) could impose its cytotoxic effect through dysregulating the RNA epigenetic modifications remains poorly defined. We systematically investigated the effects of Cr(VI) exposure on 14 kinds of modifications in mRNA of HEK293T cells. We found that Cr(VI) exposure can induce an obvious decrease of inosine in mRNA. In addition, we observed that the expression level of the adenosine deaminase acting on RNA (ADAR1) was significantly decreased upon Cr(VI) exposure, which could be responsible for the induced decrease of inosine in mRNA by Cr(VI) exposure. Together, we demonstrated that Cr(VI) could interrupt A-to-I RNA editing in mRNA, which may eventually lead to the cytotoxicity and mutagenicity.

15.
Neurosci Res ; 2019 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-31348996

RESUMO

Astrocytes are major glial cells critically in maintaining stability of the central nervous system and functional activation of astrocytes occurs rapidly in various diseased or traumatic events. We are interested in functional changes of astrocytes during the spinal cord injury, and studied expression of nerve growth factor (NGF) in activated astrocytes by mouse model of contused spinal cord injury and cell culture experiment. It revealed that the spinal cord injury resulted in apparent activation of astrocytes and microglial cells and decreased BMS scores. A larger number of astrocytes showed immunoreactivity to proNGF in the injured spinal cord areas, and proNGF expression increased and remained high level at 7 to 14dpi, which was coincided with upregulation of glial fibrillary acidic protein. The proNGF was clearly localized in both exosome-like vesicles and cytoplasm of astrocytes in culture. Electron microscopy confirmed exosome-like vesicles with proNGF-immunoreactivity in diameter sizes of 50-100 nm. Finally, cell culture with lipopolysaccharide (LPS) experiment indicated increasing expression and release of proNGF in the astrocytes with LPS exposure. This study demonstrated that reactive astrocytes increased proNGF expression after spinal cord injury, also suggesting involvement of exosome-like proNGF transport or release in triggering neuronal apoptosis and aggravating progression of spinal cord injury.

16.
Nanoscale ; 11(25): 12388-12396, 2019 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-31215952

RESUMO

The precise diagnosis of cancer remains a great challenge; therefore, it is our research interest to develop safe, tumor-specific reagents. In this study, we designed nanovesicles derived from erythrocyte membranes; the nanovesicles are capable of recognizing tumor cells for both circulating tumor cell (CTC) capture and tumor imaging. The tumor-targeting molecules folic acid (FA) and fluorescein Cy5 were modified on the nanovesicle surface. The developed nanovesicles exhibit excellent tumor targeting ability both in vitro and in vivo for CTC capture and in tumor imaging. Compared with traditional immunomagnetic beads, the proposed nanovesicles are capable of avoiding non-specific adsorption as a derivative of red blood cells. Combined with a non-invasive means of micromanipulation, the nanometer-sized vesicles show a high purity of CTC capture (over 90%). In vivo, the nanovesicles can also be employed for efficient tumor imaging without obvious toxicity and side effects. In brief, the nanovesicles prepared herein show potential clinical application for integrated diagnosis in vitro and in vivo.


Assuntos
Carbocianinas , Eritrócitos , Neoplasias Experimentais , Células Neoplásicas Circulantes/metabolismo , Imagem Óptica , Animais , Carbocianinas/química , Carbocianinas/farmacologia , Eritrócitos/química , Eritrócitos/metabolismo , Feminino , Células HCT116 , Humanos , Células MCF-7 , Camundongos , Camundongos Endogâmicos BALB C , Neoplasias Experimentais/diagnóstico por imagem , Neoplasias Experimentais/metabolismo
17.
Nanoscale ; 11(17): 8293-8303, 2019 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-30977474

RESUMO

Capturing circulating tumor cells (CTCs) from peripheral blood for subsequent analyses has shown potential in precision medicine for cancer patients. Broad as the prospect is, there are still some challenges that hamper its clinical applications. One of the challenges is to maintain the viability of the captured cells during the capturing and releasing processes. Herein, we have described a composite material that could encapsulate a magnetic Fe3O4 core in a MIL-100 shell (MMs), which could respond to pH changes and modify the anti-EpCAM antibody (anti-EpCAM-MMs) on the surface of MIL-100. After the anti-EpCAM-MMs captured the cells, there was no need for additional conditions but with the acidic environment during the cell culture process, MIL-100 could realize automatic degradation, leading to cell self-release. This self-release model could not only improve the cell viability, but could also reduce the steps of the release process and save human and material resources simultaneously. In addition, we combined clinical patients' case diagnosis with the DNA sequencing and next generation of RNA sequencing technologies in the hope of precision medicine for patients in the future.


Assuntos
Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Estruturas Metalorgânicas/química , Células Neoplásicas Circulantes/metabolismo , Anticorpos Imobilizados/química , Anticorpos Imobilizados/imunologia , Carcinoma Hepatocelular/genética , Linhagem Celular Tumoral , Sobrevivência Celular , Molécula de Adesão da Célula Epitelial/imunologia , Óxido Ferroso-Férrico/química , Humanos , Neoplasias Hepáticas/genética , Nanopartículas de Magnetita/química , Masculino , Pessoa de Meia-Idade , Mutação , Células Neoplásicas Circulantes/patologia , Transcriptoma , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo
18.
Chronic Dis Transl Med ; 5(1): 44-52, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30993263

RESUMO

Objective: To explore genes potentially co-expressed with cyclin E in gastric cancer and discover possible targets for gastric cancer treatment. Methods: The Cancer Genome Atlas (TCGA) stomach adenocarcinoma sequencing data were used to predict genes co-expressed with cyclin E. Co-expression genes predicted by cBioPortal online analysis with Pearson correlation coefficient ≥0.4 were analyzed by gene ontology (GO) enrichment annotation using the PANTHER online platform (Ver. 7). Interactions between proteins encoded by these genes were analyzed using the STRING online platform (Ver. 10.5) and Cytoscape software (Ver. 3.5.1). Genes displaying a high degree of connection were analyzed by transcription factor enrichment prediction using FunRich software (Ver. 3). The significant transcription factor and cyclin E expression levels and their impact on gastric cancer progression were analyzed by Western blotting and Kaplan-Meier survival curve analysis. Results: After filtering the co-expression gene prediction results, 78 predicted genes that included 73 protein coding genes and 5 non-coding genes with Pearson correlation coefficient ≥0.4 were selected. The expressions of the genes were considered to be correlated with cyclin E expression. Among the 78 genes co-expressed with cyclin E, 19 genes at the central of the regulatory network associated with cyclin E were discovered. Nuclear transcription factor Y subunit alpha (NF-YA) was identified as a significant transcription factor associated with cyclin E co-expressing genes. Analysis of specimen donors' clinical records revealed that high expression of NF-YA tended to be associated with increased cyclin E expression. The expression of both was associated with progression of gastric cancer. Western blotting results showed that compared with normal tissues, NF-YA and cyclin E were highly expressed in tumor tissues (P < 0.001). Survival curve analysis clearly demonstrated relatively poor overall survival of gastric cancer patients with high cyclin E or high NF-YA expression level, compared to patients with low cyclin E or NF-YA expression (P < 0.05). Conclusions: NF-YA may promote gastric cancer progression by increasing the transcription of cyclin E and other cell cycle regulatory genes. NF-YA might be a potential therapeutically useful prognostic factor for gastric cancer.

19.
Sci Total Environ ; 665: 995-1002, 2019 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-30893755

RESUMO

Although Bisphenol F (BPF), a bisphenol A (BPA) analogue with a similar chemical structure to that of BPA, is widely used in commercial products, little is known about its potential toxic effects on the reproductive neuroendocrine system in vivo. The present study aimed to comprehensively evaluate the effects of BPF on the reproductive neuroendocrine system in zebrafish and to assess the potential mechanisms underlying its association with estrogen receptor (ER) and aromatase (AROM) pathways. Long-term exposure to environmentally relevant and low levels of BPF led to increased expression of reproductive neuroendocrine-related genes (kiss1, kiss1r, gnrh3, lhß, and fshß) in the zebrafish brain, as well as increased levels of adrenocorticotropic, gonadotropin-releasing, luteinizing, and follicle-stimulating hormones in the zebrafish brain and vitellogenin in the zebrafish liver. In addition, these effects were associated with an increase in erα, erß, cyp19a, and cyp19b activity. Meanwhile, ER and AROM antagonists, alone or in combination, significantly attenuated the stimulation of kiss1, lhß, vtg, and gnrh3 expression, thereby suggesting that chronic BPF exposure affects the regulation of the reproductive neuroendocrine system through activation of the ER and AROM pathways. Moreover, since BPF and bisphenol S induced toxic and reproductive neuroendocrine effects similar to those of BPA, the current accepted usage of BPA and its analogs should be reconsidered in the future.


Assuntos
Compostos Benzidrílicos/toxicidade , Sistemas Neurossecretores/efeitos dos fármacos , Fenóis/toxicidade , Reprodução/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/fisiologia , Animais , Relação Dose-Resposta a Droga , Feminino , Masculino , Distribuição Aleatória
20.
J Clin Neurosci ; 63: 27-31, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30837110

RESUMO

Narcolepsy is a life-long neurological disorder characterized by excessive daytime sleepiness (EDS) and cataplexy. At present, Sodium oxybate, modafinil, methylphenidate and other stimulants are recommended first-line therapies for narcolepsy but are difficult to obtain in China. One hundred forty-eight patients with narcolepsy were treated with antidepressants and administered the Epworth Sleepiness Scale (ESS) and the Maintenance of Wakefulness Test (MWT) before and after treatment from August 2012 to August 2017. The subjects were followed for 1-6 years after treatment. Improvement in sleepiness, cataplexy, cataplexy-like episodes, and antidepressant side effects were assessed. There were significant differences in the mean sleep latency (MSL) and sleep onset rapid eye movement periods (SOREMPs) in MWT and ESS scores, cataplexy and cataplexy-like episodes before and after treatment (p < 0.01). Venlafaxine demonstrated significantly greater improvements in MSL in the MWT (p < 0.01). Early awakenings and dry mouth were the most common adverse effects.


Assuntos
Antidepressivos/uso terapêutico , Modafinila/uso terapêutico , Narcolepsia/tratamento farmacológico , Cloridrato de Venlafaxina/uso terapêutico , Adulto , Antidepressivos/administração & dosagem , Antidepressivos/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modafinila/administração & dosagem , Modafinila/efeitos adversos , Estudos Prospectivos , Cloridrato de Venlafaxina/administração & dosagem , Cloridrato de Venlafaxina/efeitos adversos
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