Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 65
Filtrar
1.
Biomaterials ; 255: 120141, 2020 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-32505753

RESUMO

Platelets attribute to the hypercoagulation of blood and maintenance of the tumor vascular integrity, resulting in limited intratumoral perfusion of nanoparticle into solid tumors. To overcome these adversities, we herein present an antiplatelet strategy based on erythrocyte membrane-enveloped proteinic nanoparticles that biomimic nitric oxide synthase (NOS)with co-loading of l-Arginine (LA) and photosensitizer IR783 for local NO release and inhibition of the activation of tumor-associated platelets specifically, thereby enhancing vascular permeability and accumulation of the nanoparticles in tumors. A cRGD-immobolized membrane structure is constructed to actively target platelets and cancer cells respectively, through overexpressed integrin receptors such as integrin αIIbß3 and αvß3, accelerating the inhibition of platelet activation and endocytosis of nanoparticles by tumor cells. Bio-mimicking the arginine/NO pathway in vivo, synergistical delivery of LA and IR783 enables LA molecules readily oxidize to NO with O2 that is mediated by activated IR783, the resulted NO not only retards the activity of platelets to disrupt the vascular integrity of tumor but also enhances toxicity to cancer cells. In addition, NIR-controlled release localizes the NO spatiotemporally to tumor-associated platelets and prevents undesirable systemic bleeding substantially. The reduction of the hypercoagulable state is further demonstrated by the down-regulation of tissues factor (TF) expression in tumor cells. Our study describes a promising approach to combat cancer, which advances the biomimetic NOS system as the potent therapeutic forces toward clinic applications.

2.
Sao Paulo Med J ; 138(1): 60-63, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32321107

RESUMO

BACKGROUND: Transcatheter arterial chemoembolization (TACE) is thought to prevent recurrence of hepatocellular carcinoma (HCC), but its efficacy is a matter of controversy. OBJECTIVES: We investigated the effect of preventive TACE on the tumor, nodes, metastasis (TNM) classification in cases of stage II HCC (T2N0M0) after R0 resection. DESIGN AND SETTING: Case-control study conducted in a tertiary-level public hospital. METHODS: We analyzed recurrence rates and mortality rates over time for 250 consecutive cases of HCC in TNM classification cases of stage II HCC (T2N0M0) after R0 resection. These cases were divided into patients who underwent TACE (TACE+) and presented microvascular invasion (MVI+; n = 80); TACE+ but did not present MVI (MIV-; n = 100); MVI+ but did not undergo TACE (TACE-, n = 30); and TACE-/MVI- (n = 40). RESULTS: MVI+ patients in the TACE+ group had significantly lower recurrence rates and mortality rates at one, two and three years than those in the TACE- group (all P < 0.05). Among MVI- patients, the TACE+ group did not have significantly lower recurrence rates and mortality rates at one, two and three years than the TACE- group (all P > 0.05). Regardless of whether TACE was performed or not, MVI- patients had significantly lower recurrence rates and mortality rates at two and three years after their procedures than did MVI+ patients (all P < 0.05). CONCLUSION: Recurrence rates and mortality rates for MVI+ patients were significantly higher than for MVI- patients, beyond the first year after TACE. Postoperative adjuvant TACE may be beneficial for HCC patients with MVI.


Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Estudos de Casos e Controles , Humanos , Invasividade Neoplásica , Recidiva Local de Neoplasia , Estudos Retrospectivos
3.
Life Sci ; 250: 117578, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32209426

RESUMO

AIMS: RING1 and YY1-binding protein (RYBP) is an epigenetic regulator and plays crucial roles in embryonic development. The anti-tumor effect of RYBP has been reported in several cancers recently, but the role of RYBP in esophageal squamous cell carcinoma (ESCC) has not been fully elucidated. The present study aimed to investigate the biological function and the underlying molecular mechanisms of RYBP in ESCC. MATERIALS AND METHODS: We detected the expression of RYBP in ESCC tissue microarrays (TMA) by immunohistochemistry. Cell proliferation was assessed by CCK8 and colony formation assays. Cell cycle was analyzed by flow cytometry. Gene expression was determined by transcriptome arrays, quantitative real-time PCR (qRT-PCR) and Western blot. Four-week-old male nude mice were used to evaluate the effect of RYBP in ESCC growth. KEY FINDINGS: We found that RYBP was downregulated in ESCC compared with adjacent normal tissues. A high level of RYBP expression predicted a better outcome of ESCC patients. Furthermore, overexpression of RYBP inhibited ESCC growth both in vitro and in vivo. Transcriptome arrays and functional studies showed that RYBP decreased the expression of genes related to cell cycles, especially CDC6 and CDC45, which were essential to initiate the DNA replication and G1-S transition. SIGNIFICANCE: Taken together, our study suggests that RYBP suppresses ESCC proliferation by downregulating CDC6 and CDC45, thus inhibiting the G1-S transition.


Assuntos
Proteínas de Ciclo Celular/metabolismo , Neoplasias Esofágicas/metabolismo , Carcinoma de Células Escamosas do Esôfago/metabolismo , Regulação Neoplásica da Expressão Gênica , Proteínas Nucleares/metabolismo , Proteínas Repressoras/metabolismo , Idoso , Animais , Linhagem Celular Tumoral , Proliferação de Células , Regulação para Baixo , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/patologia , Feminino , Fase G1 , Humanos , Masculino , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , Transplante de Neoplasias , Análise de Sequência com Séries de Oligonucleotídeos , Fase S , Análise Serial de Tecidos , Transcriptoma
4.
Atherosclerosis ; 298: 7-13, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32126389

RESUMO

BACKGROUND AND AIMS: The relationship of polyunsaturated fatty acids (PUFAs) with cardiovascular risk is still controversial. We aimed to determine whether erythrocyte n-3 and n-6 PUFAs are related to the risk of carotid atherosclerosis. METHODS: From 2008 to 2019, baseline erythrocyte n-3 and n-6 PUFAs were determined in a cohort of 4040 Chinese adults (40-75 ys). The intima-media thickness (IMT) at the common carotid artery (CCA) and bifurcation of the carotid artery (BIF) and carotid plaque were assessed using ultrasonography at baseline and every 3 years. RESULTS: During a median follow-up of 8.8 years, we identified the following newly diagnosed cases: 535 cases of CCAIMT thickening, 654 cases of BIFIMT thickening, and 850 cases of carotid plaque. Higher erythrocyte docosahexaenoic acid (DHA) and arachidonic acid (ARA) and lower gamma-linolenic acid (GLA) were associated with decreased risks of BIFIMT thickening. N-3 eicosatrienoic acid (ETrA), docosapentaenoic acid (DPA), and n-6 dodecylthioacetic acid (DTA) presented a significant beneficial association with carotid IMT thickening in the short-term (2.8 y) follow-up (all p trend <0.02), although the association was attenuated in the relatively long-term (8.8 y) follow-up. In addition, carotid plaque risk was found to be inversely associated with ETrA and DHA but positively associated with alpha-linolenic acid (ALA). N-6 linolenic acid (LA) and eicosadienoic acid (EDA) were not significantly associated with carotid atherosclerosis risk. CONCLUSIONS: Higher erythrocyte very-long-chain n-3 and n-6 PUFAs (especially DHA and ARA) and lower erythrocyte GLA are associated with lower carotid atherosclerosis risk, suggesting potential cardioprotective roles of very-long-chain PUFAs.

5.
Life Sci ; 246: 117366, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32001266

RESUMO

BACKGROUND: Hydroxychloroquine exhibits synergistic anticancer properties as an adjuvant. However, the role and molecular mechanisms underlying of HCQ as monotherapy for lung adenocarcinoma (LUAD) have yet to be elucidated. METHODS: We assessed the antitumor effects of HCQ in LUAD cells through a series of in vitro and in vivo assays. GEO database and R packages were used to predict molecular mechanisms of HCQ in the treatment of lung adenocarcinoma, followed by verification of gene expression and subcellular localization via immunoblotting, immunofluorescent and immunohistochemistry assays. RESULTS: We showed the phenotypic effects that HCQ inhibited cell growth, induced apoptosis and cell cycle arrest at G1/S transition in A549 and PC-9 cells, which was associated with inhibition of CDK2, CDK4, CyclinD1 and CyclinE, but up-regulation of p21 and p27Kip1. Bioinformatic analysis predicted that 63 targets related to HCQ and LUAD were mainly enriched in JAK-STAT and FoxO pathways. Then, we observed that HCQ decreased the phosphorylation of STAT3, but increased the expression of FoxO3a and its accumulation in the nucleus. The specific STAT3 inhibitor cryptotanshinon augmented the HCQ-induced upregulation and nuclear translocation of FoxO3a. In addition, HCQ increased the expression of p27Kip1, which was impaired by FoxO3a blockade with siRNA. Finally, ablation of p27Kip1 expression abrogated the cytotoxicity of HCQ. More importantly, similar results were further confirmed in vivo. CONCLUSIONS: Taken together, this study suggests that STAT3/FoxO3a/p27Kip1 signaling pathway is involved in the anticancer effects of HCQ, and provides preliminary evidence for therapeutic prospects of HCQ alone in LUAD.


Assuntos
Adenocarcinoma/tratamento farmacológico , Antineoplásicos/uso terapêutico , Proteína Forkhead Box O3/metabolismo , Hidroxicloroquina/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Fator de Transcrição STAT3/metabolismo , Células A549 , Transporte Ativo do Núcleo Celular/efeitos dos fármacos , Adenocarcinoma/metabolismo , Animais , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Neoplasias Pulmonares/metabolismo , Camundongos Nus , Transplante de Neoplasias
6.
Säo Paulo med. j ; 138(1): 60-63, Jan.-Feb. 2020. tab
Artigo em Inglês | LILACS-Express | ID: biblio-1099382

RESUMO

ABSTRACT BACKGROUND: Transcatheter arterial chemoembolization (TACE) is thought to prevent recurrence of hepatocellular carcinoma (HCC), but its efficacy is a matter of controversy. OBJECTIVES: We investigated the effect of preventive TACE on the tumor, nodes, metastasis (TNM) classification in cases of stage II HCC (T2N0M0) after R0 resection. DESIGN AND SETTING: Case-control study conducted in a tertiary-level public hospital. METHODS: We analyzed recurrence rates and mortality rates over time for 250 consecutive cases of HCC in TNM classification cases of stage II HCC (T2N0M0) after R0 resection. These cases were divided into patients who underwent TACE (TACE+) and presented microvascular invasion (MVI+; n = 80); TACE+ but did not present MVI (MIV−; n = 100); MVI+ but did not undergo TACE (TACE−, n = 30); and TACE−/MVI− (n = 40). RESULTS: MVI+ patients in the TACE+ group had significantly lower recurrence rates and mortality rates at one, two and three years than those in the TACE- group (all P < 0.05). Among MVI- patients, the TACE+ group did not have significantly lower recurrence rates and mortality rates at one, two and three years than the TACE- group (all P > 0.05). Regardless of whether TACE was performed or not, MVI− patients had significantly lower recurrence rates and mortality rates at two and three years after their procedures than did MVI+ patients (all P < 0.05). CONCLUSION: Recurrence rates and mortality rates for MVI+ patients were significantly higher than for MVI− patients, beyond the first year after TACE. Postoperative adjuvant TACE may be beneficial for HCC patients with MVI.

7.
Cell Death Differ ; 27(8): 2344-2362, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32051546

RESUMO

Rab5 is a master regulator for endosome biogenesis and transport while its in vivo physiological function remains elusive. Here, we find that Rab5a is upregulated in several in vivo and in vitro myogenesis models. By generating myogenic Rab5a-deficient mice, we uncover the essential roles of Rab5a in regulating skeletal muscle regeneration. We further reveal that Rab5a promotes myoblast differentiation and directly interacts with insulin receptor substrate 1 (IRS1), an essential scaffold protein for propagating IGF signaling. Rab5a interacts with IRS1 in a GTP-dependent manner and this interaction is enhanced upon IGF-1 activation and myogenic differentiation. We subsequently identify that the arginine 207 and 222 of IRS1 and tyrosine 82, 89, and 90 of Rab5a are the critical amino acid residues for mediating the association. Mechanistically, Rab5a modulates IRS1 activation by coordinating the association between IRS1 and the IGF receptor (IGFR) and regulating the intracellular membrane targeting of IRS1. Both myogenesis-induced and IGF-evoked AKT-mTOR signaling are dependent on Rab5a. Myogenic deletion of Rab5a also reduces the activation of AKT-mTOR signaling during skeletal muscle regeneration. Taken together, our study uncovers the physiological function of Rab5a in regulating muscle regeneration and delineates the novel role of Rab5a as a critical switch controlling AKT-mTOR signaling by activating IRS1.

8.
Elife ; 92020 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-31944179

RESUMO

Oligodendrocytes (OLs) myelinate axons and provide electrical insulation and trophic support for neurons in the central nervous system (CNS). Platelet-derived growth factor (PDGF) is critical for steady-state number and differentiation of oligodendrocyte precursor cells (OPCs), but its downstream targets are unclear. Here, we show for the first time that Gab1, an adaptor protein of receptor tyrosine kinase, is specifically expressed in OL lineage cells and is an essential effector of PDGF signaling in OPCs in mice. Gab1 is downregulated by PDGF stimulation and upregulated during OPC differentiation. Conditional deletions of Gab1 in OLs cause CNS hypomyelination by affecting OPC differentiation. Moreover, Gab1 binds to downstream GSK3ß and regulated its activity, and thereby affects the nuclear accumulation of ß-catenin and the expression of a number of transcription factors critical to myelination. Our work uncovers a novel downstream target of PDGF signaling, which is essential to OPC differentiation and CNS myelination.

9.
J Bioenerg Biomembr ; 52(2): 113-121, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31965456

RESUMO

Although mitochondrial metabolism has recently gained attention as a promising therapeutic strategy in cancer, little is known on the impact of mitochondrial respiration inhibition on oral tongue squamous cell carcinoma (OTSCC). Using in vitro and in vivo OTSCC models, our work demonstrates that inducing mitochondrial dysfunction by anti-malarial drug artesunate is effective in targeting OTSCC stem-cell like and bulk cells. Artesunate inhibits anchorage-independent colony formation, proliferation and survival in all tested OTSCC cell lines although with varying efficacy. Artesunate displays preferential anti-OTSCC activity by sparing normal cells. Mechanism analysis indicates that artesunate inhibits mitochondrial respiration via suppressing mitochondrial complex I and II but not IV or V, resulting in oxidative stress and damage. Interestingly, OTSCC cells that are more sensitive to artesunate have higher level of basal mitochondrial respiration and reversed respiratory capacity compared to those with less sensitivity to artesunate, suggesting the varying dependence on mitochondrial respiration among OTSCC cell lines. In addition, artesunate induces oxidative stress and damage in cells with low sensitivity to a less extent than in those with high sensitivity. We confirm that mitochondrial respiration inhibition is required for the action of artesunate in OTSCC. Mitochondrial dysfunction by artesunate further activates AMPK and suppresses Akt/mTOR. Importantly, the in vitro observations are reproducible in vivo OTSCC xenograft mouse model. Our findings provide pre-clinical evidence on the efficacy of artesunate and emphasize the therapeutic value of targeting mitochondrial respiration in OTSCC.

10.
J Gastrointest Surg ; 23(11): 2111-2118, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30895428

RESUMO

PURPOSE: To evaluate the survival benefit of combining radiotherapy with surgery in locally advanced esophageal squamous cell carcinoma (ESCC) patients aged over 65. METHODS: Using the SEER database, we selected patients age ≥ 65 years that were diagnosed as locally advanced ESCC during 2004-2013. Cancer-specific survival (CSS) was examined using the Kaplan-Meier analysis and compared by the log-rank test. Univariable and multivariable Cox proportional hazard models were established to identify possible prognostic factors. RESULTS: A total of 972 cases were included in the study. For surgical patients aged 65-79 years, 74 patients (32.9%) were treated by surgery alone and 122 patients (54.2%) had received additional neoadjuvant radiotherapy (NRT). NRT + surgery was associated with improved CSS comparing with surgery alone (HR, 0.58; 95%CI, 0.39 to 0.85; P = 0.005). In subgroup analysis, NRT was associated with improved CSS for patients aged 65-74 years (2-year CSS 56.6% versus 39.6%, P = 0.026). No significant differences of progonosis was observed for different treatment groups in 75-79 years patients (P = 0.972). CONCLUSIONS: In this SEER-based study, the addition of neoadjuvant radiotherapy before surgery was associated with improved CSS for locally advanced ESCC patients aged 65 to 74 years.

12.
JCI Insight ; 4(4)2019 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-30821712

RESUMO

Immunotherapy has emerged as a promising approach to treat cancer. However, partial responses across multiple clinical trials support the significance of characterizing intertumor and intratumor heterogeneity to achieve better clinical results and as potential tools in selecting patients for different types of cancer immunotherapies. Yet, the type of heterogeneity that informs clinical outcome and patient selection has not been fully explored. In particular, the lack of characterization of immune response-related genes in cancer cells hinders the further development of metrics to select and optimize immunotherapy. Therefore, we analyzed single-cell RNA-Seq data from lung adenocarcinoma patients and cell lines to characterize the intratumor heterogeneity of immune response-related genes and demonstrated their potential impact on the efficacy of immunotherapy. We discovered that IFN-γ signaling pathway genes are heterogeneously expressed and coregulated with other genes in single cancer cells, including MHC class II (MHCII) genes. The downregulation of genes in IFN-γ signaling pathways in cell lines corresponds to an acquired resistance phenotype. Moreover, analysis of 2 groups of tumor-restricted antigens, namely neoantigens and cancer testis antigens, revealed heterogeneity in their expression in single cells. These analyses provide a rationale for applying multiantigen combinatorial therapies to prevent tumor escape and establish a basis for future development of prognostic metrics based on intratumor heterogeneity.


Assuntos
Adenocarcinoma de Pulmão/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Regulação Neoplásica da Expressão Gênica/imunologia , Neoplasias Pulmonares/genética , Evasão Tumoral/genética , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/imunologia , Adenocarcinoma de Pulmão/mortalidade , Antineoplásicos Imunológicos/farmacologia , Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Linhagem Celular Tumoral , Conjuntos de Dados como Assunto , Regulação para Baixo , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Genes MHC da Classe II/imunologia , Heterogeneidade Genética , Humanos , Interferon gama/imunologia , Interferon gama/metabolismo , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Medicina de Precisão/métodos , Prognóstico , RNA-Seq , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Transdução de Sinais/imunologia , Análise de Célula Única/métodos , Resultado do Tratamento , Evasão Tumoral/efeitos dos fármacos , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia , Sequenciamento Completo do Exoma
13.
Trends Cancer ; 5(2): 85-94, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30755308

RESUMO

Advances in immune profiling techniques have dramatically changed the cancer immunotherapy and monitoring landscape. High-throughput protein and gene expression technologies have paved the way for the discovery of therapeutic targets and biomarkers, and have made monitoring therapeutic response possible through the ability to independently assay the phenotype, specificity, exhaustion status, and lineage of single T cells. Although valuable insights into response profiling have been gained with current technologies, it has become evident that single-method profiling is insufficient to accurately capture an antitumor T cell response. We discuss and propose new methods that combine multiple axes of analysis to provide a comprehensive analysis of T cell repertoire in the fight against cancer.

14.
Cell Death Differ ; 26(9): 1859-1860, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30546073

RESUMO

Since the publication of the article, the authors became aware that Figs. 1c, 5k and 6m contained errors in representative image and PAS score in control groups. The corrected Figs. 1c, 5k, and 6m are given below, and the figure legends are the same as original.

15.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 44(12): 1338-1343, 2019 Dec 28.
Artigo em Chinês | MEDLINE | ID: mdl-31969497

RESUMO

OBJECTIVE: To investigate the effects of thanatos-associated protein 11 (THAP11) on the proliferation and apoptosis of esophageal cancer cell and the underlying mechanism.
 Methods: Expression of THAP11 in human esophageal epithelial cells (Het-1A) and esophageal cancer cells (Eca109, TE-1, Ec 9706) were detected by Western blotting. Esophageal cancer TE-1 cells were divided into 3 groups: a normal control (NC) group, a negative control (LV-NC) group and a THAP11 (LV-THAP11) group. Then the cell proliferation were detected by MTT assay, cell apoptosis were detected by flow cytometry, caspase-3 and caspase-9 levels were detected by caspases kits. Ubiquitination of p53 was determined in esophageal cancer TE-1 cells.
 Results: Expression of THAP11 was reduced in esophageal cancer cells compared with human esophageal epithelial cells (P<0.05). After transfection with LV-THAP11 in TE-1 cells, cell viability was reduced (P<0.05), while apoptosis rate and caspase-3 and caspase-9 levels were increased (P<0.05), indicating that THAP11 inhibited growth of esophageal cancer cells. In addition, the THAP11 increased the levels of p53 (P<0.05) and inhibited the ubiquitination of p53 regulated by MDM2. 
 Conclusion: THAP11 may inhibit the proliferation of esophageal cancer cells by inhibiting ubiquitination of p53.


Assuntos
Neoplasias Esofágicas , Proteínas Repressoras/metabolismo , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Humanos , Proteína Supressora de Tumor p53 , Ubiquitinação
16.
Nat Biotechnol ; 2018 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-30418433

RESUMO

We present tetramer-associated T-cell receptor sequencing (TetTCR-seq) to link T cell receptor (TCR) sequences to their cognate antigens in single cells at high throughput. Binding is determined using a library of DNA-barcoded antigen tetramers that is rapidly generated by in vitro transcription and translation. We applied TetTCR-seq to identify patterns in TCR cross-reactivity with cancer neoantigens and to rapidly isolate neoantigen-specific TCRs with no cross-reactivity to the wild-type antigen.

17.
FEMS Microbiol Lett ; 365(15)2018 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-29982506

RESUMO

The microbes associated with black corals remain poorly studied. The present study is the first attempt to investigate microbial community structure in the black corals Antipathes ceylonensis and A. dichotoma from the South China Sea by using high-throughput Illumina sequencing. A total of 52 bacterial and 3 archaeal phyla were recovered in this study, suggesting the black corals harboured highly diverse microbial communities. Among the 55 microbial phyla, Proteobacteria, Firmicutes, Bacteroidetes, Chloroflexi, Acidobacteria and Actinobacteria dominated in the two black corals from the South China Sea. Although most of the microbial phyla recovered from the two black corals have been reported in previous studies on coral-associated microbes, eight bacterial phyla including Synergistetes, Thermi, AncK6, GNO2, NKB19, NC10, WWE1 and GAL15, and the archaeal phylum Parvarchaeota are reported for the first time from corals in this study, which expands our knowledge about the diversity of coral-associated microbes. The comparison of microbial communities in the different black coral species indicated that A. ceylonensis harboured few abundant bacterial genera such as Citrobacter and Pseudomonas, whereas a high diversity of rare bacterial genera (<1% abundance), such as Winogradskyella and Rubricoccus, was detected only in A. dichotoma. These results suggested that the microbial community in black corals exhibited species-specific variation.


Assuntos
Antozoários/microbiologia , Archaea/isolamento & purificação , Bactérias/isolamento & purificação , Microbiota , Animais , Archaea/classificação , Archaea/genética , Bactérias/classificação , Bactérias/genética , Biodiversidade , China , Sequenciamento de Nucleotídeos em Larga Escala , Filogenia
18.
Sci Immunol ; 3(22)2018 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-29626170

RESUMO

Follicular helper CD4+ T cells (TFH) play an integral role in promoting B cell differentiation and affinity maturation. Whereas TFH cell frequencies are increased in lymph nodes (LNs) from individuals infected with HIV, humoral immunity remains impaired during chronic HIV infection. Whether HIV inhibits TFH responses in LNs remains unclear. Advances in this area have been limited by the difficulty of accessing human lymphoid tissues. Here, we combined high-dimensional mass cytometry with T cell receptor repertoire sequencing to interrogate the composition of TFH cells in primary human LNs. We found evidence for intact antigen-driven clonal expansion of TFH cells and selective utilization of specific complementarity-determining region 3 (CDR3) motifs during chronic HIV infection, but the resulting TFH cells acquired an activation-related TFH cell signature characterized by interleukin-21 (IL-21) dominance. These IL-21+ TFH cells contained an oligoclonal HIV-reactive population that preferentially accumulated in patients with severe HIV infection and was associated with aberrant B cell distribution in the same LN. These data indicate that TFH cells remain capable of responding to HIV antigens during chronic HIV infection but become functionally skewed and oligoclonally restricted under persistent antigen stimulation.


Assuntos
Infecções por HIV/imunologia , Linfonodos/imunologia , Receptores de Antígenos de Linfócitos T/imunologia , Linfócitos T Auxiliares-Indutores/imunologia , Adolescente , Adulto , Sequência de Aminoácidos , Animais , Linfócitos B/imunologia , Feminino , Humanos , Interleucinas/imunologia , Interleucinas/metabolismo , Ativação Linfocitária/imunologia , Masculino , Pessoa de Meia-Idade , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos de Linfócitos T/metabolismo , Linfócitos T Auxiliares-Indutores/metabolismo , Adulto Jovem
19.
Accid Anal Prev ; 117: 368-380, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29530303

RESUMO

The use of statistical models for analyzing traffic safety (crash) data has been well-established. However, time series techniques have traditionally been underrepresented in the corresponding literature, due to challenges in data collection, along with a limited knowledge of proper methodology. In recent years, new types of high-resolution traffic safety data, especially in measuring driver behavior, have made time series modeling techniques an increasingly salient topic of study. Yet there remains a dearth of information to guide analysts in their use. This paper provides an overview of the state of the art in using time series models in traffic safety research, and discusses some of the fundamental techniques and considerations in classic time series modeling. It also presents ongoing and future opportunities for expanding the use of time series models, and explores newer modeling techniques, including computational intelligence models, which hold promise in effectively handling ever-larger data sets. The information contained herein is meant to guide safety researchers in understanding this broad area of transportation data analysis, and provide a framework for understanding safety trends that can influence policy-making.


Assuntos
Acidentes de Trânsito/estatística & dados numéricos , Condução de Veículo/psicologia , Modelos Estatísticos , Segurança , Estudos de Tempo e Movimento , Coleta de Dados/métodos , Planejamento Ambiental , Humanos , Pesquisa , Projetos de Pesquisa
20.
Oncol Lett ; 15(3): 3127-3132, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29435046

RESUMO

The role of long non-coding RNAs (lncRNAs) in the carcinogenesis and progression of tumors has been receiving increasing attention. Colon cancer-associated transcript 2 (CCAT2), a type of oncogenic lncRNA, is regarded as a novel biomarker of poor prognosis and metastasis in various types of cancer. However, the molecular contributions of CCAT2 to gastric cancer (GC) progression remain largely unclear. The aim of the present study was to demonstrate the effect of silencing CCAT2 on the biological behavior of GC BGC-823 cells and illustrate the potential underlying molecular mechanisms. A short hairpin RNA interference plasmid pRNAT-U6.1-CCAT2 targeting CCAT2 was successfully constructed. At 48 h after transfection with the interference plasmid, the survival rate of BGC-823 cells was significantly decreased, as determined by the MTT assay. In addition, RT-qPCR results revealed that CCAT2 gene expression was effectively suppressed by the transfection, while POU domain class 5 transcription factor 1B (POU5F1B) gene expression was significantly decreased. Terminal deoxynucleotidyl transferase dUTP nick end labeling assay further revealed that the apoptotic index was significantly higher in the interference group. Western blot analysis also demonstrated that the expression of beclin-1 protein was significantly increased, whereas the expression levels of phosphoinositide 3-kinase (PI3K) and mammalian target of rapamycin (mTOR) proteins were downregulated in the interference group. In conclusion, CCAT2 was able to positively regulate the expression of POU5F1B gene. Furthermore, silencing of CCAT2 gene inhibited the proliferation of BGC-823 cells, as well as induced apoptosis and autophagy in BGC-823 cells, by suppression of the PI3K/mTOR signaling pathways.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA