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1.
Oncoimmunology ; 10(1): 1976439, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34721946

RESUMO

Spatial information on the tumor immune microenvironment is of clinical relevance. Here, we aimed to quantify the spatial heterogeneity of lymphocytes and cancer cells and evaluated its prognostic value in patients with nasopharyngeal carcinoma (NPC). The scanned immunohistochemistry images of 336 NPC patients from two different hospitals were used to generate cell density maps for tumor and immune cells. Then, Getis-Ord hotspot analysis, a spatial statistic method used to describe species biodiversity in ecological habitats, was applied to identify cancer, immune, and immune-cancer hotspots. The results showed that cancer hotspots were not associated with any of the studied clinical outcomes, while immune-cancer hotspots predicted worse overall survival (OS) in the training cohort. In contrast, a high immune hotspot score was significantly associated with better OS (HR 0.41, 95% CI 0.22-0.77, P = .006), disease-free survival (DFS) (HR 0.43, 95% CI 0.24-0.75, P = .003) and distant metastasis-free survival (DMFS) (HR 0.40, 95% CI 0.20-0.81, P = .011) in NPC patients in the training cohort, and similar associations were also evident in the validation cohort. Importantly, multivariate analysis revealed that the immune hotspot score remained an independent prognostic indicator for OS, DFS, and DMFS in both cohorts. We explored the spatial heterogeneity of cancer cells and lymphocytes in the tumor microenvironment of NPC patients using digital pathology and ecological analysis methods and further constructed three spatial scores. Our study demonstrates that spatial variation may aid in the identification of the clinical prognosis of NPC patients, but further investigation is needed.

3.
Plant Biotechnol J ; 19(12): 2501-2516, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34342129

RESUMO

The Orchidaceae is of economic and ecological importance and constitutes ˜10% of all seed plant species. Here, we report a genome physical map for Cymbidium sinense, a well-known species belonging to genus Cymbidium that has thousands of natural variation varieties of flower organs, flower and leaf colours and also referred as the King of Fragrance, which make it arose into a unique cultural symbol in China. The high-quality chromosome-scale genome assembly was 3.52 Gb in size, 29 638 protein-coding genes were predicted, and evidence for whole-genome duplication shared with other orchids was provided. Marked amplification of cytochrome- and photosystem-related genes was observed, which was consistent with the shade tolerance and dark green leaves of C. sinense. Extensive duplication of MADS-box genes, and the resulting subfunctional and expressional differentiation, was associated with regulation of species-specific flower traits, including wild-type and mutant-type floral patterning, seasonal flowering and ecological adaption. CsSEP4 was originally found to positively regulate gynostemium development. The CsSVP genes and their interaction proteins CsAP1 and CsSOC1 were significantly expanded and involved in the regulation of low-temperature-dependent flowering. Important genetic clues to the colourful leaf traits, purple-black flowers and volatile trait in C. sinense were also found. The results provide new insights into the molecular mechanisms of important phenotypic traits of Cymbidium and its evolution and serve as a powerful platform for future evolutionary studies and molecular breeding of orchids.

4.
Aging (Albany NY) ; 13(5): 7147-7165, 2021 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-33658397

RESUMO

Whether tenofovir disoproxil fumarate (TDF) is superior to entecavir in reducing hepatocellular carcinoma (HCC) risk among treatment-naïve chronic hepatitis B (CHB) patients remains controversial. We aimed to clarify this controversy. Several databases, including PubMed and Embase, were retrieved through November 2020. Cohort studies comparing the effectiveness of TDF and entecavir in reducing HCC incidence among treatment-naïve CHB patients were included if they reported multivariable-adjusted or propensity-score-matched risk estimates. A random-effects model was used to pool hazard ratios (HRs). Thirteen cohort studies, involving 4097 HCC cases and 80202 CHB patients, were included. Multivariable-adjusted meta-analysis revealed no significant difference in HCC incidence between TDF and entecavir groups (HR 0.86, 95% confidence interval 0.72-1.04), which was consistent with propensity-score-matched meta-analysis (HR 0.83, 95% confidence interval 0.66-1.03). Subgroup analysis showed that the observed similarity of TDF to entecavir for HCC prevention persisted in studies with follow-up length of ≥4 years but not in those with follow-up length of <4 years (Pinteraction<0.01). In conclusion, TDF is similar to entecavir in reducing HCC incidence among treatment-naïve CHB patients. Heterogeneous results of included studies may result from their disparity in follow-up length. Our findings should be treated with caution and need to be further confirmed.


Assuntos
Antivirais/uso terapêutico , Carcinoma Hepatocelular/prevenção & controle , Guanina/análogos & derivados , Hepatite B Crônica/tratamento farmacológico , Neoplasias Hepáticas/prevenção & controle , Tenofovir/uso terapêutico , Carcinoma Hepatocelular/etiologia , Guanina/uso terapêutico , Humanos , Neoplasias Hepáticas/etiologia , Fatores de Risco
5.
Mol Cancer ; 20(1): 14, 2021 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-33430876

RESUMO

Currently, there is no strong evidence of the well-established biomarkers for immune checkpoint inhibitors (ICIs) in nasopharyngeal carcinoma (NPC). Here, we aimed to reveal the heterogeneity of tumour microenvironment (TME) through virtual microdissection of gene expression profiles. An immune-enriched subtype was identified in 38% (43/113) of patients, which was characterized by significant enrichment of immune cells or immune responses. The remaining patients were therefore classified as a non-Immune Subtype (non-IS), which exhibited highly proliferative features. Then we identified a tumour immune evasion state within the immune-enriched subtype (18/43, 42%), in which high expression of exclusion- and dysfunction-related signatures was observed. These subgroups were designated the Evaded and Active Immune Subtype (E-IS and A-IS), respectively. We further demonstrated that A-IS predicted favourable survival and improved ICI response as compared to E-IS and non-IS. In summary, this study introduces the novel immune subtypes and demonstrates their feasibility in tailoring immunotherapeutic strategies.


Assuntos
Heterogeneidade Genética , Imunoterapia , Carcinoma Nasofaríngeo/imunologia , Carcinoma Nasofaríngeo/terapia , Microambiente Tumoral , Estudos de Coortes , Genoma Humano , Humanos , Carcinoma Nasofaríngeo/genética , Prognóstico , Reprodutibilidade dos Testes , Microambiente Tumoral/genética
6.
J Natl Cancer Inst ; 113(4): 471-480, 2021 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-33094348

RESUMO

BACKGROUND: Induction chemotherapy (IC) followed by concurrent chemoradiotherapy is the mainstay treatment for patients with locoregionally advanced nasopharyngeal carcinoma. However, some patients obtain little benefit and experience unnecessary toxicities from IC. We intended to develop a gene-expression signature that can identify beneficiaries of IC. METHODS: We screened chemosensitivity-related genes by comparing gene-expression profiles of patients with short-term tumor response or nonresponse to IC (n = 95) using microarray analysis. Chemosensitivity-related genes were quantified by digital expression profiling in a training cohort (n = 342) to obtain a gene signature. We then validated this gene signature in the clinical trial cohort (n = 187) and an external independent cohort (n = 240). Tests of statistical significance are 2-sided. RESULTS: We identified 43 chemosensitivity-related genes associated with the short-term tumor response to IC. In the training cohort, a 6-gene signature was developed that was highly accurate at predicting the short-term tumor response to IC (area under the curve [AUC] = 0.87, sensitivity = 87.5%, specificity = 75.6%). We further found that IC conferred failure-free survival benefits only in patients in the benefit group (hazard ratio [HR] = 0.54, 95% confidence interval [CI] = 0.34 to 0.87; P = .01) and not on those in the no-benefit group (HR = 1.25, 95% CI = 0.62 to 2.51; P = .53). In the clinical trial cohort, the 6-gene signature was also highly accurate at predicting the tumor response (AUC = 0.82, sensitivity = 87.5%, specificity = 71.8%) and indicated failure-free survival benefits. In the external independent cohort, similar results were observed. CONCLUSIONS: The 6-gene signature can help select beneficiaries of IC and lay a foundation for a more individualized therapeutic strategy for locoregionally advanced nasopharyngeal carcinoma patients.


Assuntos
Expressão Gênica , Quimioterapia de Indução , Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/genética , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/genética , Adulto , Idoso , Área Sob a Curva , Estudos de Coortes , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Perfilação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/mortalidade , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/mortalidade , Neoplasias Nasofaríngeas/patologia , Sensibilidade e Especificidade , Resultado do Tratamento
8.
Cell Res ; 30(11): 1024-1042, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32686767

RESUMO

Nasopharyngeal carcinoma (NPC) is an aggressive malignancy with extremely skewed ethnic and geographic distributions. Increasing evidence indicates that targeting the tumor microenvironment (TME) represents a promising therapeutic approach in NPC, highlighting an urgent need to deepen the understanding of the complex NPC TME. Here, we generated single-cell transcriptome profiles for 7581 malignant cells and 40,285 immune cells from fifteen primary NPC tumors and one normal sample. We revealed malignant signatures capturing intratumoral transcriptional heterogeneity and predicting aggressiveness of malignant cells. Diverse immune cell subtypes were identified, including novel subtypes such as CLEC9A+ dendritic cells (DCs). We further revealed transcriptional regulators underlying immune cell diversity, and cell-cell interaction analyses highlighted promising immunotherapeutic targets in NPC. Moreover, we established the immune subtype-specific signatures, and demonstrated that the signatures of macrophages, plasmacytoid dendritic cells (pDCs), CLEC9A+ DCs, natural killer (NK) cells, and plasma cells were significantly associated with improved survival outcomes in NPC. Taken together, our findings represent a unique resource providing in-depth insights into the cellular heterogeneity of NPC TME and highlight potential biomarkers for anticancer treatment and risk stratification, laying a new foundation for precision therapies in NPC.


Assuntos
Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/imunologia , Análise de Célula Única , Transcriptoma/genética , Linfócitos B/imunologia , Comunicação Celular , Diferenciação Celular , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Imunidade , Células Matadoras Naturais/imunologia , Macrófagos/metabolismo , Monócitos/metabolismo , Células Mieloides/metabolismo , Carcinoma Nasofaríngeo/patologia , Fenótipo , Prognóstico , Processos Estocásticos , Análise de Sobrevida , Linfócitos T/imunologia , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia
9.
J Immunother Cancer ; 8(2)2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32690665

RESUMO

BACKGROUND: Tumor-infiltrating lymphocytes have been reported as prognostic markers in tumors. We aimed to assess the prognostic value of total T cell (CD3+) density, cytotoxic T cell (CD8+) density and memory T cell (CD45RO+) density in patients with nasopharyngeal carcinoma (NPC). METHODS: The expression of CD3, CD8 and CD45RO was detected by immunohistochemistry in the training (n=221) and validation cohorts (n=115). The densities of these three markers were quantified by digital pathology both in the tumor and stroma. Then, we developed the immune score based on the density of these three markers and further analyzed its prognostic value. RESULTS: The high density of CD3+, CD8+ and CD45RO+ T cells both in the tumor and/or stroma were significantly associated with the decrease in mortality in the training cohort, respectively. High immune score predicted a prolonged overall survival (OS) (HR 0.34, 95% CI 0.18 to 0.64, p=0.001, disease-free survival (DFS) (HR 0.44, 95% CI 0.25 to 0.78, p=0.005) and distant metastasis-free survival (DMFS) (HR 0.43, 95% CI 0.21 to 0.87, p=0.018) in NPC patients. The findings were confirmed in the validation cohort. Multivariate analysis revealed that immune score remained an independent prognostic indicator for OS, DFS and DMFS. In addition, we established a nomogram with the integration of all independent variables to predict individual risk of death. CONCLUSIONS: We established an immune score model, which provides a reliable estimate of the risk of death, disease progress and distant metastasis in NPC patients.


Assuntos
Linfócitos do Interstício Tumoral/imunologia , Carcinoma Nasofaríngeo/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/mortalidade , Prognóstico , Análise de Sobrevida
10.
Chemistry ; 26(54): 12472-12480, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32578255

RESUMO

In this work, pyrazine (A), aminopyrazine (B), quinoxaline (C), and 5,6,7,8-tetrahydroquinoxaline (D) have been screened out among a large number of pyrazine derivatives to construct Hofmann-type metal-organic frameworks (MOFs) Fe(L)[M(CN)4 ] (M=Pt, Pd) with similar 3D pillared-layer structures. X-ray single-crystal diffraction reveals that the alternate linkage between M and FeII ions through cyano bridges forms the 2D extended metal cyanide sheets, and ligands A-D acted as vertical columns to connect the 2D sheets to give 3D pillared-layer structures. Subsequently, a series of bivariate MOFs were constructed by pairwise combination of the four ligands A-D, which were confirmed by 1 H NMR, PXRD, FTIR, and Raman spectroscopy. The results demonstrated that ligand size and crystallization rate play a dominant role in constructing bivariate Hofmann-type MOFs. More importantly, the spin-crossover (SCO) properties of the bivariate MOFs can be finely tuned by adjusting the proportion of the two pillared ligands in the 3D Hofmann-type structures. Remarkably, the spin transition temperatures, Tc ↑ and Tc ↓ of Fe(A)x (B)1-x [Pt(CN)4 ] (x=0 to 1) can be adjusted from 239 to 254 K and from 248 to 284 K, respectively. Meanwhile, the width of the hysteresis loops can be widened from 9 to 30 K. Changing Pt to Pd, the hysteresis loops of Fe(A)x (B)1-x [Pd(CN)4 ] can be tuned from 9 (Tc ↑=215 K, Tc ↓=206 K) to 24 K (Tc ↑=300 K, Tc ↓=276 K). This research provides wider implications in the development of advanced bistable materials, especially in precisely regulating SCO properties.

11.
Mol Immunol ; 122: 69-79, 2020 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-32305690

RESUMO

Recent studies have shown that aberrant activation of the complement system plays an important role in the pathogenesis of preeclampsia. There is evidence to suggest that aberrant activation of the complement system may already be present during the first trimester. Here, we performed a prospective study in which peripheral blood samples were collected from 500 women during pregnancy. Twenty-one patients (41 specimens) suffering from preeclampsia later in pregnancy were classified into the study group, and sixty-three gravidas with normal pregnancies (136 specimens) were selected as the control group. The plasma concentrations of complement factor B (CFB), C1q, complement factor H (CFH), C3c, C4, C3a, C5a and soluble C5b-9 (sC5b-9) were measured. The levels of CFB (P = 0.004), CFH (P = 0.002), C1q (P = 0.044), C3c (P = 0.032) and C4 (P = 0.015) were significantly higher in preeclampsia than in normal pregnancy during the first trimester, and these levels became similar to those in normal pregnancy thereafter. Before the onset of preeclampsia, the levels of C3a, C5a and sC5b-9 in the preeclampsia group were similar to those in control group even in late pregnancy. C3a levels showed a significant positive correlation with C5a in normal pregnancy (r=0.658, P<0.01) but not in preeclampsia (r = 0.001, P = 1).Thus, we found that aberrant activation of the complement system in patients with preeclampsia was initiated during the first trimester but returned to normal pregnancy levels in the second trimester. At the same time, there is aberrant regulation of complement activation at the C3a-C5a level in preeclampsia during pregnancy.

12.
Cells ; 9(3)2020 02 27.
Artigo em Inglês | MEDLINE | ID: mdl-32120844

RESUMO

Epigenetic regulation plays an important role in the development and progression of nasopharyngeal carcinoma (NPC), but the epigenetic mechanisms underlying NPC metastasis remain poorly understood. Here, we demonstrate that hypermethylation of the UCHL1 promoter leads to its downregulation in NPC. Restoration of UCHL1 inhibited the migration and invasion of NPC cells in vitro and in vivo, and knockdown of UCHL1 promoted NPC cell migration and invasion in vitro and in vivo. Importantly, we found that UCHL1 interacts with CTTN, and may function as a ligase promoting CTTN degradation by increasing K48-linked ubiquitination of CTTN. Additionally, restoration of CTTN in NPC cells that overexpressed UCHL1 rescued UCHL1 suppressive effects on NPC cell migration and invasion, which indicated that CTTN is a functional target of UCHL1 in NPC. Our findings revealed that UCHL1 acts as a tumor suppressor gene in NPC and thus provided a novel therapeutic target for NPC treatment.


Assuntos
Cortactina/metabolismo , Metilação de DNA/genética , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/patologia , Proteólise , Ubiquitina Tiolesterase/genética , Animais , Linhagem Celular Tumoral , Movimento Celular/genética , Regulação para Baixo/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Células HEK293 , Humanos , Lisina/metabolismo , Camundongos Endogâmicos BALB C , Camundongos Nus , Invasividade Neoplásica , Metástase Neoplásica , Regiões Promotoras Genéticas , Ligação Proteica , Ubiquitina Tiolesterase/metabolismo , Ubiquitinação
13.
Eat Weight Disord ; 25(6): 1651-1661, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31728924

RESUMO

PURPOSE: Vitamin D insufficiency and obesity are recognized as worldwide concerns and have been linked with each other. New anthropometric indices reflect visceral obesity better than traditional anthropometric indices. Our aim was to identify the specific correlations of novel and traditional anthropometric indices with 25-hydroxyvitamin D (25(OH)D) concentrations by sex and age. METHODS: Cross-sectional data on sociodemographic characteristics, lifestyle factors, clinical characteristics and biochemical measurements were collected for 12,617 Chinese adults. Four traditional anthropometric indices, body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR) and waist-to-height ratio (WHtR), and two novel anthropometric indices, body roundness index (BRI) and body shape index (ABSI), were calculated. RESULTS: In both sexes, the mean values of BMI, WC, WHtR and BRI tended to increase with 25(OH)D insufficiency, regardless of adjustment (all P < 0.05). Males with insufficient 25(OH)D had increased odds of obesity (assessed by BMI, WC, WHtR, BRI and ABSI) compared to the odds of males with sufficient 25(OH)D. Females with insufficient 25(OH)D had a higher chance of general obesity (assessed by BMI). Low 25(OH)D status was associated with indicators of obesity only in participants aged 45-64 years in both sexes. CONCLUSION: A inverse association between obesity and lower vitamin D levels was found. Moreover, in addition to BMI, novel indicators of visceral adiposity, such as BRI and ABSI, were associated with lower 25(OH)D serum concentrations in males. The effects of optimizing vitamin D levels in obese Chinese adults need further examination, particularly in middle-aged males. LEVEL OF EVIDENCE: Level V, cross-sectional descriptive study.


Assuntos
Vitamina D , Adulto , Antropometria , Índice de Massa Corporal , China , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Circunferência da Cintura , Relação Cintura-Quadril
14.
Am J Reprod Immunol ; 83(2): e13202, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31646704

RESUMO

PROBLEM: The complement system plays a key role in normal placentation, and delicate regulation of complement system activation is critical for successful pregnancy. Therefore, establishing a normal range of complement components during pregnancy is important for clinical evaluation and research. METHODS: We performed a prospective study to investigate the normal range of complement components in circulation during different stages of pregnancy. Plasma concentrations of complement factor B (CFB), C1q, complement factor H (CFH), C3, C3c, and C4 were measured using an immunoturbidimetric assay; mannan-binding lectin (MBL), C3a, C5a, and soluble C5b-9 (sC5b-9) levels at different time points of pregnancy were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: A total of 733 plasma samples were collected from 362 women with a normal pregnancy and 65 samples from non-pregnant women. In the first trimester of pregnancy, the levels of CFB, CFH, MBL, C3c, C4, and C3a were 414.5 ± 85.9 mg/L (95% CI for mean: 402.4-426.6 mg/L), 381.0 ± 89.0 mg/L (95% CI for mean: 368.5-393.6 mg/L), 4274.5 ± 2752 ng/mL (95% CI for mean: 3881.1-4656.4 ng/mL), 1346.9 ± 419.8 mg/L (95% CI for mean: 1287.7-1406.0 mg/L), 357.4 ± 101.8 mg/L (95% CI for mean: 343.0-371.7 mg/L), and 182.5 ± 150.0 ng/mL (95% CI for mean: 186.9-229.1 ng/mL), respectively. The levels of C3 and C4 increased gradually throughout pregnancy. The levels of C1q, C5a, and sC5b-9 in the first and second trimesters were nearly the same as those in non-pregnant women. CONCLUSION: The results of this study show that pregnancy itself may influence the plasma levels of complement system components.


Assuntos
Proteínas do Sistema Complemento/análise , Gravidez/sangue , Adulto , Ativação do Complemento , Ensaio de Imunoadsorção Enzimática , Feminino , Seguimentos , Humanos , Resultado da Gravidez , Trimestres da Gravidez/sangue , Estudos Prospectivos , Valores de Referência
15.
Nat Prod Res ; : 1-8, 2019 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-31815549

RESUMO

Two new lignans, noreucol A (1) and (+)-epicycloolivil (2), along with seven known compounds (3-9) were isolated from the aqueous extract of Eucommia ulmoides Oliver. Compound 1 was a new norlignan and 2 was an epimer at C-7 of (+)-cycloolivil (3). Their structures were elucidated by spectroscopic methods, and the absolute configurations of new compounds were determined by conformational analysis and DFT theoretic electronic circular dichroism spectra calculations. In addition, the neuroprotective activity of compounds 1-3 against glutamate-induced HT-22 cells injury were evaluated, and only compound 1 exhibited moderate effect at the concentrations ranging from 10 ∼ 50 µM.

16.
J Immunother Cancer ; 7(1): 298, 2019 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-31722750

RESUMO

BACKGROUND: Immunotherapy, especially immune checkpoint inhibition, has provided powerful tools against cancer. We aimed to detect the expression of common immune checkpoints and evaluate their prognostic values in nasopharyngeal carcinoma (NPC). METHODS: The expression of 9 immune checkpoints consistent with 13 features was detected in the training cohort (n = 208) by immunohistochemistry and quantified by computational pathology. Then, the LASSO cox regression model was used to construct an immune checkpoint-based signature (ICS), which was validated in a validation cohort containing 125 patients. RESULTS: High positive expression of PD-L1 and B7-H4 was observed in tumour cells (TCs), whereas PD-L1, B7-H3, B7-H4, IDO-1, VISTA, ICOS and OX40 were highly expressed in tumour-associated immune cells (TAICs). Eight of the 13 immune features were associated with patient overall survival, and an ICS classifier consisting of 5 features (B7-H3TAIC, IDO-1TAIC, VISTATAIC, ICOSTAIC, and LAG3TAIC) was established. Patients with high-risk scores in the training cohort had shorter overall (P < 0.001), disease-free (P = 0.002), and distant metastasis-free survival (P = 0.004), which were confirmed in the validation cohort. Multivariate analysis revealed that the ICS classifier was an independent prognostic factor. A combination of the ICS classifier and TNM stage had better prognostic value than the TNM stage alone. In addition, the ICS classifier was significantly associated with survivals in patients with high EBV-DNA load. CONCLUSIONS: We determined the expression status of nine immune checkpoints consistent with 13 features in NPC and further constructed an ICS prognostic model, which might add prognostic value to the TNM staging system.


Assuntos
Carcinoma Nasofaríngeo/imunologia , Neoplasias Nasofaríngeas/imunologia , Antígenos CD/imunologia , Antígenos B7/imunologia , Antígeno B7-H1/imunologia , Biologia Computacional , Receptor Celular 2 do Vírus da Hepatite A/imunologia , Humanos , Indolamina-Pirrol 2,3,-Dioxigenase/imunologia , Proteína Coestimuladora de Linfócitos T Induzíveis/imunologia , Estimativa de Kaplan-Meier , Carcinoma Nasofaríngeo/mortalidade , Neoplasias Nasofaríngeas/mortalidade , Estadiamento de Neoplasias , Prognóstico , Receptores OX40/imunologia , Inibidor 1 da Ativação de Células T com Domínio V-Set/imunologia
17.
Nat Prod Bioprospect ; 9(5): 329-336, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31630376

RESUMO

Aqueous ethanol extracts of powdered stems of Dendrobium loddigesii afforded three new phenolics including threo-7-O-ethyl-9-O-(4-hydroxyphenyl)propionyl-guaiacylglycerol (1), (R)-4,5,4'-trihydroxy-3,3',α-trimethoxybibenzyl (2) and (S)-5,5',7-trihydroxy-3',4'-dimethoxyflavanone (3), together with eleven known analogues. Their structures were determined by extensive spectroscopic analysis. To identify natural antioxidants, whitening, and anti-aging agents, the abilities of these phenolics were assessed to scavenge the 1,2-diphenyl-2-picrylhydrazyl (DPPH) radical, their abilities to inhibit tyrosinase production, and their abilities to stimulate collagen production by human dermal fibroblasts-adult (HDFa) assay. It was found that compounds 1, 4-8, 13 and 14 exhibited significant DPPH radical scavenging activities, compound 10 exhibited tyrosinase inhibitory activity (IC50 37.904 µg/mL), and compound 9 showed significant collagen production with an EC50 value of 3.182 µg/mL. These results suggest that phenolic constituents from D. loddigesii may be candidate antioxidants, skin-whitening and/or anti-aging agents.

18.
Nat Prod Res ; : 1-6, 2019 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-31542946

RESUMO

Two new lanostane-type triterpenoids characterized with farnesyl hydroquinone moieties, ganocalidoins A (1) and B (2), were isolated from the fruiting body of Ganoderma calidophilum, together with two known tripterpenes (3-4). The structures of compounds 1 and 2 were determined by extensive spectroscopic data including HRESIMS, 1D and 2D NMR. Ganocalidoins A and B showed anti-oxidant capacity with IC50 values of 38.7 ± 2.8 and 34.2 ± 1.8 µM, respectively. The compounds did not show tyrosinase inhibition activity.

19.
Mikrochim Acta ; 186(8): 576, 2019 07 25.
Artigo em Inglês | MEDLINE | ID: mdl-31346739

RESUMO

A composite probe has been developed for fluorometric determination and imaging of phosphate in real water samples and in cells. The method is based on the use of weakly blue fluorescent bromine-doped carbon dots (C-dots) containing aromatic carbon-bromine groups and loaded with Fe3+ ions. The carboxy, phenolic hydroxy and aldehyde groups on the surface of the C-dots can coordinate with Fe3+ to form an adsorbed complex that reduces the blue fluorescence through an inner filter effect. If phosphate is added, it will capture Fe3+ on the surface of C-dots and restore fluorescence by ~88% via a displacement approach. The probe, best operated at excitation/emission maxima of 370/418 nm, has a linear response in the 0.4 to 22 µM phosphate concentration range and a 0.25 µM of detection limit. The relative standard deviation (at a phosphate level of 8.0 µM) is 3.6% (for n = 5). The method was applied to confocal imaging of phosphate in HeLa cells. Graphical abstractSchematic representation of the synthesis of bromine-doped carbon dots (C-dots) by a "one-step" approach. They are shown to be capable of (a) detecting phosphate in real water samples through the displacement approach, and (b) of imaging intracellular phosphate.


Assuntos
Compostos Férricos/química , Corantes Fluorescentes/química , Fosfatos/análise , Pontos Quânticos/química , Espectrometria de Fluorescência , Bromo/química , Carbono/química , Água Doce/análise , Células HeLa , Humanos , Íons/química , Limite de Detecção , Microscopia Confocal
20.
J Zhejiang Univ Sci B ; 20(4): 343-354, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30932379

RESUMO

Rice stripe virus (RSV) causes dramatic losses in rice production worldwide. In this study, two monoclonal antibodies (MAbs) 16E6 and 11C1 against RSV and a colloidal gold-based immunochromatographic strip were developed for specific, sensitive, and rapid detection of RSV in rice plant and planthopper samples. The MAb 16E6 was conjugated with colloidal gold and the MAb 11C1 was coated on the test line of the nitrocellulose membrane of the test strip. The specificity of the test strip was confirmed by a positive reaction to RSV-infected rice plants and small brown planthopper (SBPH), and negative reactions to five other rice viruses, healthy rice plants, four other vectors of five rice viruses, and non-viruliferous SBPH. Sensitivity analyses showed that the test strip could detect the virus in RSV-infected rice plant tissue crude extracts diluted to 1:20 480 (w/v, g/mL), and in individual viruliferous SBPH homogenate diluted to 1:2560 (individual SPBH/µL). The validity of the developed strip was further confirmed by tests using field-collected rice and SBPH samples. This newly developed test strip is a low-cost, fast, and easy-to-use tool for on-site detection of RSV infection during field epidemiological studies and paddy field surveys, and thus can benefit decision-making for RSV management in the field.


Assuntos
Cromatografia de Afinidade/métodos , Doenças das Plantas/virologia , Tenuivirus/isolamento & purificação , Anticorpos Monoclonais/química , China , Colódio/química , Coloides/química , Coloide de Ouro/química , Teste de Materiais , Membranas Artificiais , Oryza/virologia , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Especificidade da Espécie
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