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1.
Front Med ; 2020 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-32146606

RESUMO

Oncolytic virotherapy (OVT) is a novel form of immunotherapy using natural or genetically modified viruses to selectively replicate in and kill malignant cells. Many genetically modified oncolytic viruses (OVs) with enhanced tumor targeting, antitumor efficacy, and safety have been generated, and some of which have been assessed in clinical trials. Combining OVT with other immunotherapies can remarkably enhance the antitumor efficacy. In this work, we review the use of wild-type viruses in OVT and the strategies for OV genetic modification. We also review and discuss the combinations of OVT with other immunotherapies.

2.
Microb Pathog ; 143: 104092, 2020 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-32145322

RESUMO

Aeromonas veronii is a widely distributed novel pathogen that can affect humans and animals, it can cause sepsis in fish with high mortality and serious economic losses to aquaculture. In the study, the gut microbiome of the infected and uninfected grass carp with Aeromonas veronii were analyzed probiotics and pathogenic bacteria by the Miseq high-throughput sequencing, the results showed that the infected fish were significantly higher in Proteobacteria, Firmicutes, Fusobacteria, and the immune factors in liver and kidney were up-regulated by qRT-PCR. In order to effectively inhibit the pathogen, we screened an actinomycete strain and had good antibacterial effect on Aeromonas veronii. The new antagonistic bacteria was named as Streptomyces flavotricini X101, the whole genome sequencing revealed that the metabolic process was most active. After grass carp was inoculated with the minimum inhibitory concentration of 900 µg/mL of the strain's fermentation supernatant, then Aeromonas veronii was injected, we found that the pathological symptoms such as body surface, anus and abdominal congestion were alleviated by H&E staining. Cellular experiments showed that it wasn't toxic to liver cells of grass carp. Overall, this is the first study of changes in intestinal flora, phenotype, and immune factors in grass crap infected with Aeromonas veronii, it had important theoretical significance and application value for immunization and prevention.

3.
Int J Surg ; 76: 163-170, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32173614

RESUMO

BACKGROUND: Recurrence is still major obstacle to long-term survival in laryngeal squamous cell carcinoma (LSCC). We aimed to establish and validate a nomogram to precisely predict recurrence probability in patients with LSCC. METHODS: A total of 283 consecutive patients with LSCC received curative-intend surgery between 2011 and 2014 at were enrolled in this study. Subsequently, 283 LSCC patients were randomly assigned to a training cohort (N = 171) and a validation cohort (N = 112) in a 3:2 ratio. According to the results of multivariable Cox regression analysis in the training cohort, we developed a nomogram. The predictive accuracy and discriminative ability of the nomogram were evaluated by calibration curve and concordance index (C-index), and compared with TNM stage system by C-index, receiver operating characteristic (ROC) analysis. Decision curve analysis (DCA) was performed to estimate clinical value of our nomogram. RESULTS: Six independent factors rooted in multivariable analysis of the training cohort to predict recurrence were age, tumor site, smoking, alcohol, N stage and hemoglobin, which were all integrated into the nomogram. The calibration curve for the probability of recurrence presented that the nomogram-based predictions were in good correspondence with actual observations. The C-index of the nomogram was 0.81 (0.75-0.88), and the area under curve (AUC) of nomogram in predicting recurrence free survival (RFS) was 0.894, which were significantly better than traditional TNM stage. Decision curve analysis further affirmed that our nomogram had a larger net benefit than TNM stage. The results were confirmed in the validation cohort. CONCLUSION: A risk prediction nomogram for patients with LSCC, incorporating readily assessable clinicopathologic variables, generates more accurate estimations of the recurrence probability when compared TNM stage alone, but still needs additional data before being used in clinical implications.

4.
Transl Res ; 219: 30-44, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32119844

RESUMO

Accurately prognostic evaluation of patients with stage I-II pancreatic ductal adenocarcinoma (PDAC) is of importance to treatment decision and patient management. Most previously reported prognostic signatures were based on risk scores summarized from quantitative expression measurements of signature genes, which are susceptible to experimental batch effects and impractical for clinical applications. Based on the within-sample relative expression orderings of genes, we developed a robust qualitative transcriptional prognostic signature, consisting of 64 gene pairs (64-GPS), to predict the overall survival (OS) of 161 stage I-II PDAC patients in the training dataset who were treated with surgery only. Samples were classified into the high-risk group when at least 25 of 64 gene pairs suggested it was at high risk. The signature was successfully validated in 324 samples from 6 independent datasets produced by different laboratories. All samples in the low-risk group had significantly better OS than samples in the high-risk group. Multivariate Cox regression analyses showed that the 64-GPS remained significantly associated with the OS of patients after adjusting available clinical factors. Transcriptomic analysis of the 2 prognostic subgroups showed that the differential expression signals were highly reproducible in all datasets, whereas the differences between samples grouped by the TNM staging system were weak and irreproducible. The epigenomic analysis showed that the epigenetic alternations may cause consistently transcriptional changes between the 2 different prognostic groups. The genomic analysis revealed that mutation­induced disturbances in several key genes, such as LRMDA, MAPK10, and CREBBP, might lead to poor prognosis for PDAC patients. Conclusively, the 64-GPS can robustly predict the prognosis of patients with stage I-II PDAC, which provides theoretical basis for clinical individualized treatment.

5.
Artigo em Chinês | MEDLINE | ID: mdl-32086918

RESUMO

Objective:The aim of this study is to investigate the effect of sublingual immunotherapy with Dermatophagoides Farinae on the expression of specific IgG4(sIgG4) in patients with allergic rhinitis (AR) in Hainan area. Method:Seventy-two patients with dust-mite allergic rhinitis, all three generations of whom were local islanders in Hainan, were randomly divided into control group(36 cases) and SLIT group(36 cases). sIgG4 and sIgE expression levels were detected before treatment, 6 months after treatment, 12 months after treatment, and 18 months after treatment. The patient's symptom score, medication score, VAS score and adverse reactions was also assessed. Finally, through statistical analysis of the relevant data collected at 4 time points in the two groups of patients, the efficacy, safety and changes of sIgG4 antibody expression level in patients with allergic rhinitis receiving sublingual specific immunotherapy in Hainan were observed. Result:Symptoms scores, medication scores and VAS scores were significantly improved in the SLIT group after treatment compared with before treatment(P<0.05), and serum sIgG4 increased significantly(P<0.01), serum sIgE showed no significant change(P>0.05). In the control group, symptom scores, medication scores and VAS scores were also significantly improved compared with before treatment(P<0.05), while serum sIgG4 and sIgE showed no significant change(P>0.05). When comparing the two groups, Symptoms scores, medication scores and VAS scores of the SLIT group were significantly lower than those of the control group at 12 months and 18 months after treatment(P<0.05). sIgG4 expression levels in the SLIT group were significantly higher than those in the control group after 6, 12 and 18 months of treatment(P<0.01). There was no significant difference in sIgE expression level between the two groups(P>0.05). No severe systemic adverse reactions occurred in the two groups, and 3 patients showed mild adverse reactions in the SLIT group. Conclusion:Sublingual immunotherapy of Dermatophagoides Farinae was effective and could increase the expression of sIgG4 in patients with Dermatophagoides farinae AR, sIgG4 is expected to be an immunological marker for the objective evaluation of the clinical efficacy of Hapten.


Assuntos
Antígenos de Dermatophagoides/uso terapêutico , Imunoglobulina G/sangue , Rinite Alérgica/terapia , Imunoterapia Sublingual , Animais , China , Dermatophagoides farinae , Humanos , Rinite Alérgica/imunologia , Resultado do Tratamento
6.
Nature ; 577(7789): 216-220, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31915399

RESUMO

Precise protein sequencing and folding are believed to generate the structure and chemical diversity of natural channels1,2, both of which are essential to synthetically achieve proton transport performance comparable to that seen in natural systems. Geometrically defined channels have been fabricated using peptides, DNAs, carbon nanotubes, sequence-defined polymers and organic frameworks3-13. However, none of these channels rivals the performance observed in their natural counterparts. Here we show that without forming an atomically structured channel, four-monomer-based random heteropolymers (RHPs)14 can mimic membrane proteins and exhibit selective proton transport across lipid bilayers at a rate similar to those of natural proton channels. Statistical control over the monomer distribution in an RHP leads to segmental heterogeneity in hydrophobicity, which facilitates the insertion of single RHPs into the lipid bilayers. It also results in bilayer-spanning segments containing polar monomers that promote the formation of hydrogen-bonded chains15,16 for proton transport. Our study demonstrates the importance of the adaptability that is enabled by statistical similarity among RHP chains and of the modularity provided by the chemical diversity of monomers, to achieve uniform behaviour in heterogeneous systems. Our results also validate statistical randomness as an unexplored approach to realize protein-like behaviour at the single-polymer-chain level in a predictable manner.

7.
Nat Commun ; 11(1): 91, 2020 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-31900392

RESUMO

Prokaryotes use repetitive genomic elements termed CRISPR (clustered regularly interspaced short palindromic repeats) to destroy invading genetic molecules. Although CRISPR systems have been widely used in DNA and RNA technology, certain adverse effects do occur. For example, constitutively active CRISPR systems may lead to a certain risk of off-target effects. Here, we introduce post-synthetic masking and chemical activation of guide RNA (gRNA) to controlling CRISPR systems. An RNA structure profiling probe (2-azidomethylnicotinic acid imidazolide) is used. Moreover, we accomplish conditional control of gene editing in live cells. This proof-of-concept study demonstrates promising potential of chemical activation of gRNAs as a versatile tool for chemical biology.


Assuntos
Edição de Genes , RNA Guia/metabolismo , RNA/metabolismo , Sistemas CRISPR-Cas , Endonucleases/metabolismo , Células HeLa , Humanos , RNA/genética , RNA Guia/genética
8.
Prostate ; 80(5): 376-387, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31961962

RESUMO

BACKGROUND: The qualitative transcriptional characteristics, the within-sample relative expression orderings (REOs) of genes, are highly robust against batch effects and sample quality variations. Hence, we develop a qualitative transcriptional signature based on REOs to predict the biochemical recurrence risk of prostate cancer (PCa) patients after radical prostatectomy. METHODS: Gene pairs with REOs significantly correlated with the biochemical recurrence-free survival (BFS) were identified from 131 PCa samples in the training data set. From these gene pairs, we selected a qualitative transcriptional signature based on the within-sample REOs of gene pairs which could predict the recurrence risk of PCa patients after radical prostatectomy. RESULTS: A signature consisting of 74 gene pairs, named 74-GPS, was developed for predicting the recurrence risk of PCa patients after radical prostatectomy based on the majority voting rule that a sample was assigned as high risk when at least 37 gene pairs of the 74-GPS voted for high risk; otherwise, low risk. The signature was validated in six independent datasets produced by different platforms. In each of the validation datasets, the Kaplan-Meier survival analysis showed that the average BFS of the low-risk group was significantly better than that of the high-risk group. Analyses of multiomics data of PCa samples from TCGA suggested that both the epigenomic and genomic alternations could cause the reproducible transcriptional differences between the two different prognostic groups. CONCLUSIONS: The proposed qualitative transcriptional signature can robustly stratify PCa patients after radical prostatectomy into two groups with different recurrence risk and distinct multiomics characteristics. Hence, 74-GPS may serve as a helpful tool for guiding the management of PCa patients with radical prostatectomy at the individual level.

9.
Endocrine ; 67(2): 321-330, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31786774

RESUMO

PURPOSE: Serum complement C3 has been shown to contribute to the incidence of type 2 diabetes (T2D), but how serum complement C3 affects islet ß-cell function throughout the course of T2D is unclear. This study explored whether serum complement C3 is independently associated with changes in islet ß-cell function over time in patients with T2D. METHODS: Serum complement C3 was measured, and endogenous ß-cell function was evaluated by area under the C-peptide curve (AUCcp) during an oral glucose tolerance test (OGTT) in 411 patients with T2D at baseline from 2011 to 2015. Next, 347 of those patients with available data were pooled for a final follow-up analysis from 2014 to 2018. Changes in islet ß-cell function at follow-up were evaluated by AUCcp percentage changes (ΔAUCcp%). In addition, other possible clinical risks for diabetes were also examined. RESULTS: The 347 patients included in the analysis had a diabetes duration of 4.84 ± 3.63 years at baseline. Baseline serum complement C3 (baseline C3) levels were positively correlated with baseline natural logarithm of AUCcp (lnAUCcp) (n = 347, r = 0.288, p < 0.001), and baseline C3 was independently associated with baseline lnAUCcp (ß = 0.17, t = 3.52, p < 0.001) after adjustment for baseline glycemic status and other clinical confounders by multivariate liner regression analysis. Compared with the baseline values, complement C3 changes (ΔC3) and ΔAUCcp% was -0.15 ± 0.28 mg/ml and -17.2 ± 18.4%, respectively, at a follow-up visit 4.57 ± 0.78 years later. Moreover, ΔC3 was positively correlated with ΔAUCcp% (n = 347, r = 0.302, p < 0.001). Furthermore, each 0.1 mg/ml increase in ΔC3 was associated with a higher ΔAUCcp% (1.41% [95% CI, 0.82-2.00%]) after adjusting for changes in glycemic status and other clinical confounders at follow-up. CONCLUSIONS: In addition to serum complement C3 being independently associated with islet ß-cell function at baseline, its changes were also independently associated with changes in islet ß-cell function over time in patients with T2D.

10.
Analyst ; 144(24): 7278-7282, 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31696169

RESUMO

Benefiting from the simple DNAzyme and a duplex-specific nuclease, a series of microRNA-stimulated DNAzyme logic gates were rationally assembled for the highly accurate detection of multiple low-abundant microRNA biomarkers that correspond to the specific aberrant microRNA expression patterns of cancer tissues, thus showing a great potential in early diagnosis.

11.
Syst Biol Reprod Med ; : 1-11, 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31714804

RESUMO

The objective of this study was to identify proteins that are differentially expressed in the cystic wall tissues of ovarian endometriotic cysts, simple ovarian cysts, and in normal ovarian tissues. Specimens of ovarian endometriotic cyst wall tissue, simple ovarian cyst wall tissue, and normal ovarian tissue (six specimens per group) were collected from patients who received gynecologic surgery, respectively. Differentially expressed proteins related to the ovarian endometriotic cysts were screened by use of isobaric tags for relative and absolute quantitation (iTRAQ) combined with functional annotation and bioinformatics analyses. All differentially expressed proteins related to cysts were validated using immunohistochemistry methods in recurrent and non-recurrent ovarian endometriotic cyst. A total of 359 proteins were identified as up-regulated in ovarian endometriotic cyst groups when compared with both the normal ovary and simple ovarian cyst groups. The levels of 27 proteins were >two-fold higher in the ovarian endometriotic cyst group than that in the other two groups. Of note, the five most significantly upregulated proteins were Charcot-Leyden Crystal Galectin (CLC), Defensin, alpha 1 (DEFA1), S100 calcium-binding protein A9 (S100A9), S100 calcium-binding protein A8 (S100A8), and Ferritin Light Chain (FTL). Immunohistochemistry results showed that the changes of S100A9 and S100A8 were consistent with the results shown by iTRAQ. However, no similarity of CLC, DEFA1, and FTL proteins was found between iTRAQ and immunohistochemistry. The ratio of patients with abnormally high S100A9 and S100A8 expression in the recurrent ovarian endometriotic cyst group was significantly higher than that in the non-recurrent group (P < 0.05). Our data identify differentially expressed proteins S100A9 and S100A8, and suggest they may serve as novel molecular markers to predict postoperative recurrence of an ovarian endometriotic cysts.Abbreviations: iTRAQ: isobaric tags for relative and absolute quantitation; HPRD: Human Protein Reference Database; GO: Gene Ontology; KEGG: Kyoto Encyclopedia of Genes and Genomes; EM: Endometriosis; COX-2: cyclooxyenase-2; NF-kB: nuclear factor kappa-B; PR-B: progesterone receptor type B.

13.
Oncol Rep ; 42(6): 2537-2549, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31638193

RESUMO

Adipocyte infiltration in pancreatic cancer (PC) has been demonstrated to be independently associated with PC risk and an active contributor to tumor progression. However, to date, little is known about these unique pancreatic tumor­surrounding adipocytes, or their response to cancer cells. The present study utilized an in vitro indirect coculture model in which the phenotypic changes of adipocytes following exposure to PC cells were directly observed. RNA­sequencing was performed on 3T3­L1 adipocytes cultured with or without Panc­1 cancer cells, and significant changes were identified at the transcriptional level. In terms of delipidation and the impaired function of glucose and lipid metabolism, coculture with tumor cells resulted in an altered metabolic phenotype in mature adipocytes. In co­cultured adipocytes, the appearance of fibroblast­like cells was observed, and the mesenchymal cell differentiation pathway was enriched following the integrated analysis into the transcriptome. In addition, reverse transcription­quantitative PCR analyses of co­cultured adipocytes revealed a loss in gene expression of mature adipocyte markers, and a gain in gene expression of fibroblast­specific markers. It was also confirmed that newly generated cancer­associated adipocytes could facilitate the invasive capacities of the tumor, and may contribute to PC stromal remodeling. The present study supports a novel concept that reprogramming of stromal adipocytes orchestrated by PC cells may generate cancer­associated adipocytes with activated phenotypes, which may ultimately drive pancreatic tumor progression.

14.
Med Sci Monit ; 25: 8025-8033, 2019 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-31654522

RESUMO

BACKGROUND This study aimed to investigate the effects of xanthoxyletin, a plant-derived coumarin, on human oral squamous cancer cells in vitro and in mouse xenografts in vivo. MATERIAL AND METHODS The study included SCC-1 human oral cancer cells and EBTr normal embryonic bovine tracheal epithelial cells, which were treated with 0 µM, 5 µM, 10 µM, and 20 µM of xanthoxyletin for 24 hours. The MTT assay assessed cell viability, and autophagy was detected by electron microscopy. Cell apoptosis was investigated using 4',6-diamidino-2-phenylindole (DAPI), annexin V, and propidium iodide (PI) fluorescence flow cytometry, which was also used to investigate the cell cycle. Protein expression was measured by Western blot. Mouse xenografts were used for the in vivo evaluation of the effects of xanthoxyletin. RESULTS Xanthoxyletin significantly inhibited the proliferation of oral cancer cells (IC50, 10-30 µM) with lower cytotoxicity for normal cells. Xanthoxyletin treatment was associated with G2/M arrest of the cell cycle and with increased apoptosis and autophagy of SCC-1 cells. Apoptosis and autophagy induced by xanthoxyletin were also associated with changes in expression of the apoptosis-associated proteins, Bax and Bcl-2, and the autophagy-associated proteins, LC3I, LC3II, Beclin 1, p62, and VSp34. Xanthoxyletin inhibited the expression of components of the signaling cascade of the MEK/ERK pathway in the SCC-1 oral cancer cells. The in vivo effects of xanthoxyletin showed inhibition of growth of mouse xenografts. CONCLUSIONS Xanthoxyletin inhibited the proliferation of human oral squamous carcinoma cells and induced apoptosis, autophagy, and cell cycle arrest by modulation of the MEK/ERK signaling pathway.

15.
Proc Natl Acad Sci U S A ; 116(38): 18943-18950, 2019 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-31484776

RESUMO

Rapid advances in genomic technologies have led to a wealth of diverse data, from which novel discoveries can be gleaned through the application of robust statistical and computational methods. Here, we describe GeneFishing, a semisupervised computational approach to reconstruct context-specific portraits of biological processes by leveraging gene-gene coexpression information. GeneFishing incorporates multiple high-dimensional statistical ideas, including dimensionality reduction, clustering, subsampling, and results aggregation, to produce robust results. To illustrate the power of our method, we applied it using 21 genes involved in cholesterol metabolism as "bait" to "fish out" (or identify) genes not previously identified as being connected to cholesterol metabolism. Using simulation and real datasets, we found that the results obtained through GeneFishing were more interesting for our study than those provided by related gene prioritization methods. In particular, application of GeneFishing to the GTEx liver RNA sequencing (RNAseq) data not only reidentified many known cholesterol-related genes, but also pointed to glyoxalase I (GLO1) as a gene implicated in cholesterol metabolism. In a follow-up experiment, we found that GLO1 knockdown in human hepatoma cell lines increased levels of cellular cholesterol ester, validating a role for GLO1 in cholesterol metabolism. In addition, we performed pantissue analysis by applying GeneFishing on various tissues and identified many potential tissue-specific cholesterol metabolism-related genes. GeneFishing appears to be a powerful tool for identifying related components of complex biological systems and may be used across a wide range of applications.

16.
World Neurosurg ; 130: 1-6, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31254713

RESUMO

BACKGROUND: Cases of multiple intracranial tumors are common; however, cases of multiple intraspinal tumors are rare. Except for cases of neurofibromatosis, it is very rare for tumors of different pathological types to exist concurrently at the same spinal level. Only 9 cases have been reported to date, with meningioma found with schwannoma in 7 cases and with neurofibroma in 2 cases. CASE DESCRIPTION: We have reported another rare case in which neurofibroma and meningioma were identified within a single dumbbell-shaped tumor at the same cervical level without neurofibromatosis. The preoperative magnetic resonance imaging findings indicated a single extra- and intradural extramedullary dumbbell-shaped neurogenic tumor on the left ventral side of the cervical spine. Intraoperatively, we found that the mass consisted of 2 pathologically different tumors. The results of surgical resection were mostly satisfactory. CONCLUSIONS: To the best of our knowledge, the present case is the first reported case of intradural neurofibroma (not meningioma) and extradural meningioma growing mixed together at the same spinal level without neurofibromatosis. The precise mechanism underlying the formation of the tumor is unknown, and multidirectional differentiation of a common progenitor cell is one possibility. Intra- and extradural exploration and component biopsies are useful for treatment planning, especially when the magnetic resonance imaging is not sufficiently sensitive for the diagnosis of coexisting tumor types.


Assuntos
Vértebras Cervicais/diagnóstico por imagem , Neoplasias Meníngeas/diagnóstico por imagem , Meningioma/diagnóstico por imagem , Neurofibroma/diagnóstico por imagem , Neurofibromatoses , Neoplasias da Coluna Vertebral/diagnóstico por imagem , Vértebras Cervicais/cirurgia , Feminino , Humanos , Neoplasias Meníngeas/complicações , Neoplasias Meníngeas/cirurgia , Meningioma/complicações , Meningioma/cirurgia , Pessoa de Meia-Idade , Neurofibroma/complicações , Neurofibroma/cirurgia , Neoplasias da Coluna Vertebral/complicações , Neoplasias da Coluna Vertebral/cirurgia
17.
Chin J Integr Med ; 25(12): 948-955, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31161441

RESUMO

Osteosarcoma is a rare primary malignancy of bone that is prone to early metastasis. Resection surgery and chemotherapeutic regimens are current standard treatments for osteosarcoma. However, the long-term survival rate of patients with osteosarcoma is low due to a high risk of metastasis. Hence, a new approach is urgently needed to improve the treatment of osteosarcoma. Compared with chemotherapy, natural active constituents isolated from herbs exhibit less adverse effects and better anti-tumor effects. This study aimed to summarize the anticancer effects of constituents of herbs on the progression and metastasis of osteosarcoma cells. It showed that many constituents of herbs inhibited osteosarcoma by targeting proliferation, matrix metalloproteinases, integrin and cadherin, and angiogenesis. The findings might be beneficial for the development of new drugs and treatment strategies.

18.
Shanghai Kou Qiang Yi Xue ; 28(1): 67-70, 2019 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-31081003

RESUMO

PURPOSE: To investigate the correlation between the expression of lncRNA PCAT-1 and clinicopathological features of oral squamous cell carcinoma. METHODS: In this study, 112 oral tissue specimens, including 60 oral squamous cell carcinoma, and 52 non-cancer oral tissues were collected from Department of Stomatology in Anhui Provincial Hospital during 2013 to 2016. Reverse transcription quantitative PCR (RT-PCR) was performed to detect the expression of PCAT-1 and c-Myc. The correlation between the levels of PCAT-1 and clinical features (age, gender, high risk habit, histological stage, cervical lymphatic metastasis, differentiation) were analyzed. Graphpad Prism 7.0 software package was used for statistical analysis. RESULTS: Significant different levels of PCAT-1 were found between the high risk habit (alcohol and tobacco) group and low risk habit group, between patients with cervical lymphnode metastasis and patients without cervical lymphnode metastasis. The expression of PCAT-1 and c-Myc were up-regulated in OSCC, and there were positive correlation between the expression of PCAT-1 and c-Myc; up-regulated expression of PCAT-1 may be associated with higher morbidity of OSCC. CONCLUSIONS: PCAT-1 is overexpressed in oral squamous cell carcinoma and is associated with higher morbidity of OSCC.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Bucais , RNA Longo não Codificante , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/metabolismo , Humanos , Linfonodos , Metástase Linfática , Morbidade , Neoplasias Bucais/diagnóstico , Neoplasias Bucais/metabolismo , Prognóstico , RNA Longo não Codificante/metabolismo
19.
Front Pharmacol ; 10: 338, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31130856

RESUMO

Benzo(a)pyrene (BaP) is a polycyclic aromatic hydrocarbon that specifically causes cancer and is widely distributed in the environment. Poly (ADP-ribosylation), as a key post-translational modification in BaP-induced carcinogenesis, is mainly catalyzed by poly (ADP-ribose) glycohydrolase (PARG) in eukaryotic organisms. Previously, it is found that PARG silencing can counteract BaP-induced carcinogenesis in vitro, but the mechanism remained unclear. In this study, we further examined this process in vivo by using heterozygous PARG knockout mice (PARG+/-). Wild-type and PARG+/- mice were individually treated with 0 or 10 µg/m3 BaP for 90 or 180 days by dynamic inhalation exposure. Pathological analysis of lung tissues showed that, with extended exposure time, carcinogenesis and injury in the lungs of WT mice was progressively worse; however, the injury was minimal and carcinogenesis was not detected in the lungs of PARG+/- mice. These results indicate that PARG gene silencing protects mice against lung cancer induced by BaP inhalation exposure. Furthermore, as the exposure time was extended, the protein phosphorylation level was down-regulated in WT mice, but up-regulated in PARG+/- mice. The relative expression of Wnt2b and Wnt5b mRNA in WT mice were significantly higher than those in the control group, but there was no significant difference in PARG+/- mice. Meanwhile, the relative expression of Wnt2b and Wnt5b proteins, as assessed by immunohistochemistry and Western blot analysis, was significantly up-regulated by BaP in WT mice; while in PARG+/- mice it was not statistically affected. Our work provides initial evidence that PARG silencing suppresses BaP induced lung cancer and stabilizes the expression of Wnt ligands, PARG gene and Wnt ligands may provide new options for the diagnosis and treatment of lung cancer.

20.
Huan Jing Ke Xue ; 40(5): 2027-2035, 2019 May 08.
Artigo em Chinês | MEDLINE | ID: mdl-31087837

RESUMO

To study the pollution characteristics, sources, and transportation process of PM2.5 and its chemical compositions in the Zhengzhou-Xinxiang region, PM2.5 samples were collected using a middle volume sampler, in Zhengzhou and Xinxiang urban areas for 30 consecutive days during the winter of 2016. The mass concentration of PM2.5 was measured gravimetrically. 17 trace metals were determined by inductively coupled plasma-mass spectrometry (ICP-MS), and 7 water-soluble ions were determined by ion chromatography. The enrichment factor (EF) method and principal component analysis were employed to determine the source apportionment. The results showed that the daily mean PM2.5 mass concentration during the winter sampling period of 2016 in Xinxiang and Zhengzhou was 223.87 µg·m-3 and 226.67 µg·m-3, respectively, which indicated that pollution levels were relatively high in both cities. The concentration of three macro elements (Al, Ca, and Fe) accounted for 50% of the total metal elements in both cities, while the heavy metals concentration was higher in Xinxiang than in Zhengzhou. The EFs of Cd, Ag, and Pb in Xinxiang were far higher than 1000, while only Cd was higher than 1000 in Zhengzhou. NO3-, SO42-, and NH4+ were the main ions in the two cities. They exceeded 94% of total water-soluble ions and existed in the forms of (NH4)2SO4 and NH4NO3. The principle component analysis showed that the main contributors to PM2.5 were a mixture of biomass combustion and secondary aerosol in Xinxiang, and a mixture of coal combustion and traffic emissions in Zhengzhou, accounting for 34.94% and 33.99% of total PM2.5 emissions, respectively.

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