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1.
Methods Mol Biol ; 2147: 163-173, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32840819

RESUMO

Functional vasculature is crucial for the maintenance of living tissues via the transport of oxygen, nutrients, and metabolic waste products. As a result, insufficient vascularization in thick engineered tissues will lead to cell death and necrosis due to mass transport and diffusional constraints. To circumvent these limitations, we describe the development of a microscale continuous optical bioprinting (µCOB) platform for 3D printing complex vascularized tissues with superior resolution and speed. By using the µCOB system, endothelial cells and other supportive cells can be printed directly into hydrogels with precisely controlled distribution and subsequent formation of lumen-like structures in vitro.

2.
Physiol Behav ; 228: 113190, 2020 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-33002497

RESUMO

BACKGROUND: Traumatic brain injury (TBI) can lead to cognitive dysfunction and motor dysfunction. TBI is a potential risk factor for subsequent dementia. Hyperphosphorylation of Tau and ApoE4 has been found in patients with TBI. A significant increase in miR-203 was also found in the peripheral blood of TBI mice. Thus, we hypothesize that miR-203 inhibitor protects against neuronal damage and behavioral deficits by inhibition of Tau phosphorylation, ApoE4 expression and apoptosis. METHODS: TBI mice were induced and treated with miR-203 inhibitor. Tau phosphorylation and ApoE4, hippocampal long-term potentiation (LTP), learning and memory, and motor function were separately detected by Western blot analysis, electrophysiology recording and behavioral assessments including Morris water maze test, beam-balance test, beam-walk test and rotarod test. Caspase-3 activity and bcl-2 expression were detected by ELISA. RESULTS: TBI induction led to increased phosphorylation of Tau and ApoE4 expression. Administration of miR-203 inhibitor suppressed TBI induced ApoE4 expression and Tau hyperphosphorylation, rescued TBI mediated hippocampal LTP deficits and hippocampus dependent learning and memory dysfunction. miR-203 inhibitor treatment also improved motor function. In addition, miR-203 inhibitor treatment inhibited neuronal apoptosis by inhibiting caspase-3 activity and increasing bcl-2 expression. CONCLUSION: miR-203 inhibitor treatment can rescue TBI-induced neural damage by inhibiting neuronal apoptosis and dementia markers like ApoE4 expression and Tau phosphorylation.

3.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(5): 1750-1756, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33067985

RESUMO

OBJECTIVE: To investigate the safety and efficacy of tumor-associated antigen-specific cytotoxic T lympho- cytes (TAA-CTL) in the treatment of multiple myeloma (MM) and non-Hodgkin lymphoma (NHL). METHODS: Peripheral blood mononuclear cells (PBMNC)of patients were collected. Dendritic cells (DC) were loaded with multiple tumor-associated antigens (TAA) (NY-ESO-1, MAGE-A3, MAGE-A4, WT1, Survivin, PRAME, LMP1 and LMP2A), then co-cultured with PBMNC to induce cytotoxic T lymphocytes (CTL). The phenotypes of cell products were detected, and the disease statuse was evaluated in 7 patients during or after infusion. The changes of TAA-CTL amount in the PBMNC of patients were measured by using IFN-γ ELISpot assay. RESULTS: TAA-CTL products were generated comprising CD3+ T cells (mean 82.98%) with a mixture of CD4+ (mean 42.09%) and CD8+ (mean 25.32%) T cells. Among them, 70% expressed effectors memory markers (CD45RO+CD62L-CCR7-). Each patient received TAA-CTL infusions for 1-4 times, and none of them showed obvious adverse reactions. The clinical symptoms and laboratory or imaging examination of 5 patients achieved positive effects. After cell therapy, the spot-forming cells (SFC) levels of most patients gradually increased and the peak often appeared about 2-3 weeks after the infusion. CONCLUSION: TAA-CTLs preliminarily show its safety and efficacy in MM and NHL patients, however, a larger population sample is needed to explore its clinical application value.

4.
Artigo em Inglês | MEDLINE | ID: mdl-33023158

RESUMO

In rural China around 60 million left-behind children (LBC) experience prolonged separation from migrant worker parents. They are vulnerable to a range of psychosocial problems. The aim of this study was to determine whether a community-based intervention consisting of Children's Centres can improve psychosocial well-being and school performance of these children. The intervention was carried out in 20 villages, for children aged 7 to 15 years, irrespective of left-behind status. Nine hundred and twenty children, 438 LBC and 256 children living with parents (RC) attended the Centres. At follow-up after one year, there were improvements compared to baseline in total difficulties (measured with the Strengths and Difficulties Questionnaire) in children left behind by both parents (p = 0.009), children left behind by one parent (p = 0.008) and RC (p = 0.05). Postintervention school performance significantly improved in both categories of LBC (p < 0.001), but not RC (p = 0.07); social support score increased in both categories of LBC (p < 0.001) and RC (p = 0.01). Findings from interviews with key stakeholders were overwhelmingly positive about the impacts. With strong local leadership and community motivation, a low-cost intervention can improve children's psychosocial well-being in these settings. Allowing communities to adapt the model to their own situation fosters local ownership, commitment, with benefits for children, parents, carers, and communities.

5.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 744-749, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33018094

RESUMO

The recent progress in recognizing low-resolution instantaneous high-density surface electromyography (HD-sEMG) images opens up new avenues for the development of more fluid and natural muscle-computer interfaces. However, the existing approaches employed a very large deep convolutional neural network (ConvNet) architecture and complex training schemes for HD-sEMG image recognition, which requires learning of >5.63 million(M) training parameters only during fine-tuning and pre-trained on a very large-scale labeled HD-sEMG training dataset, as a result, it makes high-end resource-bounded and computationally expensive. To overcome this problem, we propose S-ConvNet models, a simple yet efficient framework for learning instantaneous HD-sEMG images from scratch using random-initialization. Without using any pre-trained models, our proposed S-ConvNet demonstrate very competitive recognition accuracy to the more complex state of the art, while reducing learning parameters to only ≈ 2M and using ≈ 12 × smaller dataset. The experimental results proved that the proposed S-ConvNet is highly effective for learning discriminative features for instantaneous HD-sEMG image recognition, especially in the data and high-end resource-constrained scenarios.

6.
J Neural Eng ; 17(5): 056011, 2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-33043903

RESUMO

OBJECTIVE: Removal of common mode noise and artifacts from extracellularly measured action potentials, herein referred to as spikes, recorded with multi-electrode arrays (MEAs) which included severe noise and artifacts generated by an ultrahigh field (UHF) 16.4 Tesla magnetic resonance imaging (MRI) scanner. APPROACH: An adaptive virtual referencing (AVR) algorithm is used to remove artifacts and thus enable extraction of neural spike signals from extracellular recordings in anesthetized rat brains. A 16-channel MEA with 150-micron inter-site spacing is used, and a virtual reference is created by spatially averaging the 16 signal channels which results in a reference signal without extracellular spiking activity while preserving common mode noise and artifacts. This virtual reference signal is then used as the input to an adaptive FIR filter which optimally scales and time-shifts the reference to each specific electrode site to remove the artifacts and noise. MAIN RESULTS: By removing artifacts and reducing noise, the neural spikes at each electrode site can be well extracted, even from data originally recorded with a high noise floor due to electromagnetic interference and artifacts generated by a 16.4T MRI scanner. The AVR method enables many more spikes to be detected than would otherwise be possible. Further, the filtered spike waveforms can be well separated from each other using PCA feature extraction and semi-supervised k-means clustering. While data in a 16.4T MRI scanner contains significantly more noise and artifacts, the developed AVR method enables similar data quality to be extracted as recorded on benchtop experiments outside the MRI scanner. SIGNIFICANCE: AVR of extracellular spike signals recorded with MEAs has not been previously reported and fills a technical need by enabling low-noise extracellular spike extraction in noisy and challenging environments such as UHF MRI that will enable further study of neuro-vascular coupling at UHF.

7.
Acta Derm Venereol ; 2020 10 07.
Artigo em Inglês | MEDLINE | ID: mdl-33026095

RESUMO

Syphilis, human immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV) share transmission routes. Syphilis infection can increase the risk of acquiring and transmitting HIV in key populations. The aims of this study were to investigate the risk factors and co-infection patterns for HIV, HBV and HCV in patients with syphilis. A retrospective study was conducted of 2,412 patients with syphilis (1,922 (79.68%) with latent syphilis, 336 (13.93%) with secondary syphilis, 78 (3.23%) with primary syphil­is, 72 (2.99%) with tertiary syphilis, and 4 (0.17%) with congenital syphilis). Positive results were observed in 8.21% (134/1,620) of patients tested for HIV, 5.75% (82/1,427) for HBV, and 1.02% (14/1,374) for HCV, respectively. Multivariate logistic regression analysis found that male sex (adjusted odds ratio (AOR) 26.03; 95% confidence interval (CI) 10.37­65.36), age < 55 years, especially age group 25­34-years (AOR 8.06; 95% CI 4.16­15.61), diagnosed at the Department of Infectious Disease (AOR 19.16; 95% CI 9.74­37.69), patients from Southern China, which is a geographical area south of the Qinling-Huaihe line (AOR 1.86; 95% CI 1.06­3.26) and having a rapid plasma reagin titre ≥1:32 (AOR 1.88; 95% CI 1.12­3.15) were independently associated with HIV infection. Risk factors for HBV co-infection in patients with syphilis, including male sex (AOR 1.78; 95% CI 1.12­2.83) and living in Southern China (AOR 4.66; 95% CI, 2.36­9.17) were also identified.

8.
Radiat Res ; 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33045079

RESUMO

Radiation-induced skin injury remains a serious concern for cancer radiotherapy, radiation accidents and occupational exposure, and the damage mainly occurs due to apoptosis and reactive oxygen species (ROS) generation. There is currently no effective treatment for this disorder. The ß-catenin signaling pathway is involved in the repair and regeneration of injured tissues. However, the role of the ß-catenin signaling pathway in radiation-induced skin injury has not been reported. In this study, we demonstrated that the ß-catenin signaling pathway was activated in response to radiation and that its activation by Wnt3a, a ligand-protein involved in the ß-catenin signaling pathway, inhibited apoptosis and the production of ROS in irradiated human keratinocyte HaCaT cells and skin fibroblast WS1 cells. Additionally, Wnt3a promoted cell migration after irradiation. In a mouse model of full-thickness skin wounds combined with total-body irradiation, Wnt3a was shown to facilitate skin wound healing. The results from RNA-Seq revealed that 24 genes were upregulated and 154 were downregulated in Wnt3a-treated irradiated skin cells, and these dysregulated genes were mainly enriched in the tight junction pathway. Among them, Marvel D3 showed the most obvious difference. We further found that the activated ß-catenin signaling pathway stimulated the phosphorylation of JNK by silencing Marvel D3. Treatment of irradiated cells with SP600125, a JNK inhibitor, augmented ROS production and impeded cell migration. Furthermore, treatment with Wnt3a or transfection with Marvel D3-specific siRNAs could reverse the above effects. Taken together, these findings illustrate that activated ß-catenin signaling stimulates the activation of JNK by negatively regulating Marvel D3 to ameliorate radiation-induced skin injury.

9.
Chin Med J (Engl) ; 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-33009019

RESUMO

BACKGROUND: Accumulating evidence has revealed that circulating microRNAs (miRNAs) can serve as non-invasive biomarkers for cancer diagnosis. This study aimed to identify differentially expressed miRNAs in serum which might become potential biomarkers for non-invasive diagnosis of papillary thyroid carcinoma (PTC). METHODS: The experiment was carried out between 2015 and 2017. In the screening stage, the Exiqon miRNA quantitative real-time polymerase chain reaction (qPCR) panel was applied to select candidate miRNAs. In the following training, testing, and external validation stages, the serum samples of 100 patients and 96 healthy controls (HCs) were analyzed to compare the expression levels of the identified miRNAs. The areas under the receiver operating characteristic curves (AUCs) were calculated to assess the diagnostic value of the identified signature. RESULTS: Three miRNAs (miR-25-3p, miR-296-5p, and miR-92a-3p) in serum were consistently up-regulated in PTC patients compared with HCs. A three-miRNA panel was constructed by logistic regression analysis and showed better diagnostic performance than a single miRNA for PTC detection. The AUCs of the panel were 0.727, 0.771, and 0.862 for the training, testing, and external validation stage, respectively. Meanwhile, the panel showed stable capability in differentiating PTC patients from patients with benign goiters, with an AUC as high as 0.969. For further exploration, the three identified miRNAs were analyzed in tissue samples (23 PTC vs. 23 HCs) and serum-derived exosomes samples (24 PTC vs. 24 HCs), and the altered expression in the tumor also indicated their close relationship with PTC disease. CONCLUSION: We identify a three-miRNA panel in serum which might serve as a promising biomarker for PTC diagnosis.

10.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 5580-5583, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33019242

RESUMO

The topic of automatic detection of sleep apnea which is a respiratory sleep disorder, affecting millions of patients worldwide, is continuously being explored by researchers. Electroencephalogram signal (EEG) represents a promising tool due to its direct correlation to neural activity and ease of extraction. Here, an innovative approach is proposed to automatically detect apnea by incorporating local variations of temporal features for identifying the global feature variations over a broader window. An EEG data frame is divided into smaller sub-frames to effectively extract local feature variation within one larger frame. A fully convolutional neural network (FCNN) is proposed that will take each sub-frame of a single frame individually to extract local features. Following that, a dense classifier consisting of a series of fully connected layers is trained to analyze all the local features extracted from subframes for classifying the entire frame as apnea/non-apnea. Finally, a unique post-processing technique is applied which significantly improves accuracy. Both the EEG frame length and post-processing parameters are varied to find optimal detection conditions. Large-scale experimentation is executed on publicly available data of patients with varying apnea-hypopnea indices for performance evaluation of the suggested method.

11.
Neurotox Res ; 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33025360

RESUMO

Prenatal glucocorticoid (GC) overexposure impacts fetal hippocampal neural stem cells (NSCs) and increases the risk for relative cognitive and mood disorders in offspring. However, the precise underlying mechanisms remain elusive. Here, we treated mouse hippocampal NSCs with dexamethasone (DEX) in vitro and found that DEX inhibited cell proliferation and Sirt7 expression. In addition, prenatal mouse overexposure to DEX induced the suppression of Sirt7 in the hippocampus of offspring. Sirt7 knockdown significantly decreased the percentage of proliferating cells but did not further reduce the NSC proliferation rate in the presence of DEX, whereas Sirt7 overexpression rescued DEX-induced inhibition of hippocampal NSC proliferation. Moreover, DEX inhibited Sirt7 expression through the glucocorticoid receptor (GR), and p21 was found to mediate the functional effect of DEX-induced Sirt7 suppression. In conclusion, our data demonstrate for the first time the effect of DEX on the Sirt7-p21 pathway in hippocampal NSCs, identifying a new potential therapeutic target for prenatal GC overexposure-related neurodevelopmental disorders in offspring.

12.
Acta Pharmacol Sin ; 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-32999412

RESUMO

Metrnl, a secreted protein expressed in white adipose tissue, has been identified as a novel adipokine. It is also highly expressed in barrier tissues, including the skin, intestinal and respiratory tract epithelium in both mice and humans. Research shows that its expression is upregulated by inflammation, chronic high-fat diets, exercise, cold exposure, etc., and it plays important roles in promoting neurite extension, enhancing white fat browning, improving insulin sensitivity, modulating lipid metabolism and regulating inflammatory response, the latter implying Metrnl is a new cytokine. These studies suggest that Metrnl could be a promising biomarker and a potential therapeutic target for the related diseases. For proving this, clinical studies need to be performed to bridge the gap between bench and bedside. In this paper, we summarize the progress in recent clinical research on Metrnl. Most of these clinical studies are designed to confirm the relationship between circulating Metrnl and metabolic or cardiovascular disease (type 2 diabetes and coronary heart disease), or immune inflammation-related diseases, such as colitis, psoriasis and arthritis. Although blood Metrnl seems to fluctuate and are affected by many factors, such as drugs, physical exercise, and cold exposure, these clinical studies provide reliable clues that Metrnl is associated with coronary heart disease, inflammation-related diseases, etc. Nevertheless, the roles of Metrnl in some diseases such as nervous system diseases remain unclear, and its putative involvement should be further clarified. These studies could promote the application of Metrnl in clinic as a new therapeutic target.

13.
Chin J Integr Med ; 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-33000416

RESUMO

OBJECTIVE: To summarize current hotspots and predict the potential trends in traditional drugs of diabetes treatment for further research. METHODS: Publications on the application of traditional drugs in diabetes treatment were searched from PubMed without language limits. Highly frequent MeSH terms were identified through Bibliographic Item Co-Occurrence Matrix Builder (BICOMB). Biclustering analysis results were visualized utilizing the gCLUTO software. Finally, a strategic diagram was generated. RESULTS: Totally 2,386 relevant publications were obtained from PubMed on November 9th, 2018, and 69 highly frequent MeSH terms were identified. Biclustering analysis revealed that these highly frequent MeSH terms were classified into 7 clusters. After calculating the density and centrality of each cluster, strategy diagram was presented. Cluster 0 "Chinese medicine monomers such as antioxidant and hypoglycemic effects" was considered as the most potential research hotspot. CONCLUSIONS: In this study, we found 7 topics related to the application of traditional drugs in diabetes treatment. The molecular mechanisms of Chinese medicine monomers in diabetes could become a potential hotspot with high centricity and low density.

14.
Eur J Dermatol ; 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33052103

RESUMO

BACKGROUND: The efficacy and safety of calcipotriol plus betamethasone dipropionate gel for the treatment of scalp psoriasis has previously been demonstrated in a four-week trial in a Chinese population. OBJECTIVE: To evaluate the long-term safety and efficacy of two-compound gel in Chinese adult patients with scalp psoriasis. MATERIALS AND METHODS: A multicentre, prospective, randomized, active-controlled trial was established in which subjects were randomized (at a ratio of 4:1) to receive either two-compound gel once daily or calcipotriol scalp solution twice daily for 28 weeks. Incidence of adverse drug reactions (ADRs) of any type and adverse events (AEs) of concern associated with long-term corticosteroid use on the scalp were evaluated. RESULTS: A total of 951 subjects were randomly assigned to receive either two-compound gel (n=760) or calcipotriol scalp solution (n=191). The incidence of ADRs was significantly lower in the two-compound gel group compared with the calcipotriol scalp solution group (11.7 vs. 22.2%, p<0.001). There was no significant difference in treatment-emergent adverse events (TEAEs) associated with long-term topical corticosteroid use on the scalp (1.1% vs. 0%, p=0.369) between the two groups. A statistically significant difference in the percentage of visits with treatment success according to the Subject's Global Assessment was observed (p=0.009); more subjects had visits with 100% treatment success (15.2 vs. 6.3%) and fewer subjects had visits with 0% treatment success (23.7 vs. 30.8%) using two-compound gel compared to calcipotriol scalp solution. CONCLUSIONS: The two-compound gel was well tolerated and effective in the long-term management of scalp psoriasis in Chinese patients.

15.
Anal Chem ; 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-32955856

RESUMO

We describe an efficient decision tree searching strategy (DTSS) to boost the identification of cross-linked peptides. The DTSS approach allows the identification of a wealth of complementary information to facilitate the construction of more protein-protein interaction networks for human cell lysate, which was tested by the use of a recently reported cross-linking data set (ACS Cent. Sci. 2019, 5, 1514-1522). A variant of the PhoX-linker, named pDSPE, was synthesized and applied to cross-link Escherichia coli cell lysate to demonstrate that the acquisition of doubly charged ions can significantly improve identification results. The method can be seamlessly integrated to other search engines to maximize the number of identified cross-links.

16.
Med Sci Monit ; 26: e925991, 2020 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-32980853

RESUMO

BACKGROUND Women with normal fasting glucose (FPG) range (5.1 ≤FPG <6.09 mmol/L) in early pregnancy are at high risk of gestational diabetes mellitus (GDM). The aim of this study was to compare the effectiveness of routine antenatal care with a midwife-managed clinic service in the prevention of GDM in early pregnancy at a hospital in China. MATERIAL AND METHODS We designed a prospective observational clinical study among pregnancy women with normal fasting glucose (FPG) range (5.1 ≤FPG <6.09 mmol/L) in early pregnancy. Routine antenatal care was compared with a midwife-managed clinic service providing diet and exercise education before week 16. A 75-g OGTT was performed at weeks 24-28 for both groups. Results of OGTT and gestational weight gain were compared between the 2 groups. RESULTS Of the 592 eligible women, 296 women received the antenatal nursing clinic service and 296 were enrolled in a control group. Thirty-three women were lost to follow-up during the study, leaving 279 in the intervention group and 280 in the control group. Baseline demographic characteristics were similar between the 2 groups. GDM was diagnosed in 115 participants (41.2%) in the intervention group and 141 (50.4%) in the control group. Subgroup analysis showed a significantly lower rate of GDM in the intervention group among the No-IVF population (37.8% vs. 49.0%, P=0.01%). For pre-pregnancy BMI, significant differences were found in the incidence of GDM and maternal hypertension between the different groups, showing that the overweight group benefited most from the midwife-managed antenatal clinic service. CONCLUSIONS The midwife-managed clinic service was feasible and effective in the prevention of GDM.

17.
J Mol Graph Model ; 101: 107734, 2020 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-32931981

RESUMO

This paper presents a computational study of the adsorptive desulfurization of small aromatic sulfur compounds by conjugated microporous polymers (CMPs). The density-functional tight-binding method augmented with an R-6 dispersion correction is employed to investigate the physisorption binding mechanism and electronic properties of the CMP-aromatic sulfur complexes. We show that the widely extended π conjugation in the CMP skeletons is favorable for the non-covalent adsorption of aromatic thiophene and dibenzothiophene via π-π, H-π, and S-π interactions. The average binding energies are calculated to be -6.2 âˆ¼ -15.2 kcal/mol for CMP- thiophene/dibenzothiophene systems. For the dibenzothiophene molecule with larger size and more extended conjugation, it binds more than twice stronger to CMP than the thiophene molecule. We show that the replacement of quinoline unit to the phenylene group in the network linker effectively enhances the average binding capacities by around 0.8-1.8 kcal/mol. Our calculations theoretically demonstrate that CMPs materials are kind of promising candidates for the adsorptive desulfurization of small aromatic sulfur compounds. This paper provides useful theoretical guidance for design of novel carbon-based adsorbents for adsorptive desulfurization.

18.
Genome Med ; 12(1): 77, 2020 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-32878637

RESUMO

BACKGROUND: Long non-coding RNAs (lncRNAs) are extensively intricate in the tumorigenesis and metastasis of various cancer types. Nevertheless, the detailed molecular mechanisms of lncRNA in non-small cell lung cancer (NSCLC) still remain mainly undetermined. METHODS: qPCR was performed to verify LINC00301 expression in NSCLC clinical specimens or cell lines. Fluorescence in situ hybridization (FISH) was conducted to identify the localization of LINC00301 in NSCLC cells. Chromatin immunoprecipitation (ChIP) was subjected to validate the binding activity between FOXC1 and LINC00301 promoters. RNA immunoprecipitation (RIP) was performed to explore the binding activity between LINC00301 and EZH2. RNA pull-down followed by dot-blot, protein domain mapping, and RNA electrophoresis mobility shift assay (EMSA) were conducted to identify the detailed binding regions between LINC00301 and EZH2. Alpha assay was conducted to quantitatively assess the interaction between LINC00301 and EZH2. RESULTS: LINC00301 is highly expressed in NSCLC and closely corelated to its prognosis by analyzing the relationship between differentially expressed lncRNAs and prognosis in NSCLC samples. in vitro and in vivo experiments revealed that LINC00301 facilitates cell proliferation, releases NSCLC cell cycle arrest, promotes cell migration and invasion, and suppresses cell apoptosis in NSCLC. In addition, LINC00301 increases regulatory T cell (Treg) while decreases CD8+ T cell population in LA-4/SLN-205-derived tumors through targeting TGF-ß. The transcription factor FOXC1 mediates LINC00301 expression in NSCLC. Bioinformatics prediction and in vitro experiments indicated that LINC00301 (83-123 nucleotide [nt]) can directly bind to the enhancer of zeste homolog 2 (EZH2) (612-727 amino acid [aa]) to promote H3K27me3 at the ELL protein-associated factor 2 (EAF2) promoter. EAF2 directly binds and stabilizes von Hippel-Lindau protein (pVHL), so downregulated EAF2 augments hypoxia-inducible factor 1 α (HIF1α) expression by regulating pVHL in NSCLC cells. Moreover, we also found that LINC00301 could function as a competing endogenous RNA (ceRNA) against miR-1276 to expedite HIF1α expression in the cytoplasm of NSCLC cells. CONCLUSIONS: In summary, our present research revealed the oncogenic roles of LINC00301 in clinical specimens as well as cellular and animal experiments, illustrating the potential roles and mechanisms of the FOXC1/LINC00301/EZH2/EAF2/pVHL/HIF1α and FOXC1/LINC00301/miR-1276/HIF1α pathways, which provides novel insights and potential theraputic targets to NSCLC.

19.
Addiction ; 2020 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-32918512

RESUMO

BACKGROUND AND AIMS: Three to 10 minutes of smoking cessation advice by physicians is effective to increase quit rates, but is not routinely practised. We examined the effectiveness of physicians' very brief (approximately 30 sec) smoking cessation intervention on quit rates among Chinese outpatient smokers. DESIGN: A pragmatic, open-label, individually randomized controlled trial. SETTING: Seventy-two medical outpatient departments of hospitals and/or community health centers in Guangdong, China. PARTICIPANTS: Chinese adults who were daily cigarette smokers (n = 13 671, 99% males) were invited by their physician to participate during outpatient consultation. Smokers who were receiving smoking cessation treatment or were judged to need specialist treatment for cessation were excluded. INTERVENTIONS: The intervention group (n = 7015) received a 30-sec intervention including physician's very brief advice, a leaflet with graphic warnings and a card with contact information of available cessation services. The control group (n = 6656) received a very brief intervention on consuming vegetables and fruit. A total of 3466 participants in the intervention group were further randomized to receive a brief booster advice from trained study personnel via telephone 1 month following their doctor visit. MEASUREMENTS: The primary outcome was self-reported 7-day point prevalence abstinence (PPA) in the intervention and control groups at the 12-month follow-up. Secondary outcomes included self-reported 30-day abstinence and biochemically validated abstinence at 12-month follow-up. FINDINGS: By intention-to-treat, the intervention (versus control) group had greater self-reported 7-day abstinence [9.1 versus 7.8%, odds ratio (OR) = 1.14, 95% confidence interval (CI) = 1.03-1.26, P = 0.008] and 30-day abstinence (8.0 versus 6.9%, OR = 1.14, 95% CI = 1.03-1.27, P = 0.01) at 12-month follow-up. The effect size increased when only participants who received the intervention from compliant physicians were included (7-day PPA, OR = 1.42, 95% CI = 1.11-1.74). The group difference in biochemically validated abstinence was small (0.8 versus 0.8%, OR = 1.00, 95% CI = 0.71-1.42, P = 0.99). CONCLUSION: A 30-sec smoking cessation intervention increased self-reported abstinence among mainly male smokers in China at 12-month follow-up (risk difference = 1.3%), and should be feasible to provide in most settings and delivered by all health-care professionals.

20.
Artigo em Inglês | MEDLINE | ID: mdl-32903648

RESUMO

Scrub typhus is a zoonotic disease caused by Orientia tsutsugamushi (O. tsutsugamushi). Orientia tsutsugamushi has various genotypes and more new strains with difference in sequences increasingly appeared. Whether the accurateness of one special nested PCR method which amplifies segment instead of entire open reading frame (ORF) sequence meets the current work of identifying new strains and classifying genotypes remains to be confirmed. And the origins and evolution of this organism have not been thoroughly elucidated. Accordingly, in this study, segments and the entire ORF of the 56-kDa type-specific antigen (TSA56) gene of O. tsutsugamushi were collected, including 209 clinically isolated strains in Guangzhou, China from 2012 to 2016 and 139 reference strains worldwide. By performing phylogenetic analysis, we proved that the accurateness of the particular PCR method which almost met detection need. This re-grouping result showed that segments perfectly represented and identified strains of Karp, Boryong, Gilliam, TA763, Kawasaki and part of Kato genotype, and this accuracy is not restricted by region and time. Sequence diversification of Shimokoshi and some Kato strains made their genotyping need to consider entire ORF sequences, but their weak recognition might not be due to recombination. The frequent genetic recombination and high point mutations contributed to genetic diversification of the TSA56 gene. Major overlapping regions of most recombination events occurred between strains of the same genotype, especially Karp and Kato genotype. And cross-genotype overlapping events occurred between Karp and Boryong/Gilliam/TA763/Kato, Kato and Kawasaki/Gilliam/TA686, Boryong and TA686, and Gilliam and Kawasaki. But Segment has quite low recombination frequency and stable mutation trend from 1943 to 2016. So segment is a relatively conserved part of the TSA56 ORF as for its stable trend of genetic diversity, and it may anchor and represent the entire TSA56 ORF gene. And genetic diversity is rejected as one potential reason for the increased incidence of scrub typhus. But an occasional recombination event created an unrecognized genotype which might be due to the breakage of VD II and AD II. Additionally, strains in Guangzhou were homologous and Karp genotype was detected as a dominant.

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