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1.
Nucleic Acids Res ; 52(D1): D1193-D1200, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-37897359

RESUMO

circRNADisease v2.0 is an enhanced and reliable database that offers experimentally verified relationships between circular RNAs (circRNAs) and various diseases. It is accessible at http://cgga.org.cn/circRNADisease/ or http://cgga.org.cn:9091/circRNADisease/. The database currently includes 6998 circRNA-disease entries across multiple species, representing a remarkable 19.77-fold increase compared to the previous version. This expansion consists of a substantial rise in the number of circRNAs (from 330 to 4246), types of diseases (from 48 to 330) and covered species (from human only to 12 species). Furthermore, a new section has been introduced in the database, which collects information on circRNA-associated factors (genes, proteins and microRNAs), molecular mechanisms (molecular pathways), biological functions (proliferation, migration, invasion, etc.), tumor and/or cell line and/or patient-derived xenograft (PDX) details, and prognostic evidence in diseases. In addition, we identified 7 159 865 relationships between mutations and circRNAs among 30 TCGA cancer types. Due to notable enhancements and extensive data expansions, the circRNADisease 2.0 database has become an invaluable asset for both clinical practice and fundamental research. It enables researchers to develop a more comprehensive understanding of how circRNAs impact complex diseases.


Assuntos
Bases de Dados Genéticas , Neoplasias , RNA Circular , Humanos , Linhagem Celular , Neoplasias/genética
2.
BMC Cancer ; 23(1): 551, 2023 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-37322408

RESUMO

Polymerase I and transcript release factor (PTRF) plays a role in the regulation of gene expression and the release of RNA transcripts during transcription, which have been associated with various human diseases. However, the role of PTRF in glioma remains unclear. In this study, RNA sequencing (RNA-seq) data (n = 1022 cases) and whole-exome sequencing (WES) data (n = 286 cases) were used to characterize the PTRF expression features. Gene ontology (GO) functional enrichment analysis was used to assess the biological implication of changes in PTRF expression. As a result, the expression of PTRF was associated with malignant progression in gliomas. Meanwhile, somatic mutational profiles and copy number variations (CNV) revealed the glioma subtypes classified by PTRF expression showed distinct genomic alteration. Furthermore, GO functional enrichment analysis suggested that PTRF expression was associated with cell migration and angiogenesis, particularly during an immune response. Survival analysis confirmed that a high expression of PTRF is associated with a poor prognosis. In summary, PTRF may be a valuable factor for the diagnosis and treatment target of glioma.


Assuntos
Variações do Número de Cópias de DNA , Glioma , Humanos , Linhagem Celular Tumoral , Glioma/genética , Análise de Sobrevida
3.
Odontology ; 111(4): 982-992, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36773195

RESUMO

The aim of this study is to assess the relationship between somatosensory functional changes and inferior alveolar nerve (IAN) exposure after impacted mandibular third molars (M3M) removal. We recruited 35 patients who underwent impacted M3M extraction near the IAN. The M3Ms were extracted by combined endoscopy, piezosurgery, and contra-angle high-speed turbine handpiece. All IAN canal perforations and exposed regions were recorded and measured by endoscopy after extraction and on cone-beam computed tomography (CBCT) images before extraction. The patients were followed up 1, 7, and 35 days after surgery. A standardized quantitative sensory testing (QST) battery was performed on the lower lip skin. All of 35 cases had exposed IAN on CBCT images, 5 of which had no exposed IAN under endoscopy. For the other 30 cases, the endoscopy-measured IAN length and width were shorter than the CBCT measurements (P < 0.001). The warm and mechanical detection thresholds (MDT) on the operation side were significantly higher than the contralateral side after surgery (P < 0.05). Thermal sensory limen, MDT, and cold pain threshold were strongly correlated with the exposed IAN length and MDT also with the exposed IAN width one day after surgery. In conclusion, it was found that not all exposed IAN in CBCT images were real exposure after surgery. The intraoperative exposed IAN endoscopic measurements were smaller than by CBCT and strongly correlated with some QST parameters.


Assuntos
Dente Impactado , Traumatismos do Nervo Trigêmeo , Humanos , Dente Serotino/cirurgia , Mandíbula , Endoscopia , Extração Dentária/métodos , Dente Impactado/diagnóstico por imagem , Dente Impactado/cirurgia , Nervo Mandibular/diagnóstico por imagem , Tomografia Computadorizada de Feixe Cônico/métodos , Radiografia Panorâmica/métodos
4.
Environ Monit Assess ; 195(12): 1510, 2023 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-37989923

RESUMO

The PM2.5 (particulate matter with a diameter of fewer than 2.5 µm) has become a global topic in environmental science. The neural network that based on the non-linear regression algorithm, e.g., deep learning, is now believed to be one of the most facile and advanced approaches in PM2.5 concentration prediction. In this study, we proposed a PM2.5 predictor using deep learning as infrastructure and meteorological data as input, for predicting the next hour PM2.5 concentration in Beijing Aotizhongxin monitor point. We efficiently use the parameter's spatiotemporal correlation by concatenating the dataset with time series. The predicted PM2.5 concentration was based on meteorology changes over a period. Therefore, the accuracy would increase with the period growing. By extracting the intrinsic features between meteorological and PM2.5 concentration, a fast and accurate prediction was carried out. The R square score reached maximum of 0.98 and remained an average of 0.9295 in the whole test. The average bias of the model is 9 µg on the validation set and 1 µg on the training set. Moreover, the differences between the predictions and expectations can be further regarded as the estimation for the emission change. Such results can provide scientific advice to supervisory and policy workers.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Humanos , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Meteorologia , Monitoramento Ambiental/métodos , Material Particulado/análise , Redes Neurais de Computação , Previsões
5.
Zhongguo Zhong Yao Za Zhi ; 48(19): 5216-5234, 2023 Oct.
Artigo em Zh | MEDLINE | ID: mdl-38114111

RESUMO

The chemical constituents of Chuanzhi Tongluo Capsules were analyzed and identified using ultra-high performance liquid chromatography-quadrupole/electrostatic field orbitrap high-resolution mass spectrometry(UPLC-Q-Exactive Orbitrap-MS) to clarify the pharmacological substance basis. In addition, network pharmacology was employed to explore the mechanism of Chuanzhi Tongluo Capsules in the treatment of cerebral infarction. Gradient elution was performed using acetonitrile and 1% acetic acid in water as the mobile phase. Mass spectrometry was performed in positive and negative ion modes. Xcalibur 4.2 software was used for compound analysis, including accurate mass-to-charge ratio and MS/MS fragment information, combined with the comparison of reference standards and literature data. A total of 152 compounds were identified, including 32 organic acids, 35 flavonoids and their glycosides, 33 diterpenes, 13 phthalides, 12 triterpenes and triterpene saponins, 23 nitrogen-containing compounds, and 4 other compounds, and their fragmentation patterns were analyzed. SwissTargetPrediction, GeneCards, DAVID, and other databases were used to predict and analyze the core targets and mechanism of Chuanzhi Tongluo Capsules. Protein-protein interaction(PPI) network topology analysis identified 10 core targets, including TNF, VEGFA, EGFR, IL1B, and CTNNB1. KEGG enrichment analysis showed that Chuanzhi Tongluo Capsules mainly exerted their effects through the regulation of lipid and atherosclerosis, glycoproteins in cancer, MicroRNAs in cancer, fluid shear stress, and atherosclerosis-related pathways. Molecular docking was performed between the key constituents and core targets, and the results demonstrated a strong binding affinity between the key constituents of Chuanzhi Tongluo Capsules and the core targets. This study comprehensively elucidated the chemical constituents of Chuanzhi Tongluo Capsules and explored the core targets and mechanism in the treatment of cerebral infarction based on network pharmacology, providing a scientific reference for the study of the pharmacological substance basis and formulation quality standards of Chuanzhi Tongluo Capsules.


Assuntos
Aterosclerose , Medicamentos de Ervas Chinesas , Neoplasias , Humanos , Espectrometria de Massas em Tandem/métodos , Cromatografia Líquida de Alta Pressão/métodos , Simulação de Acoplamento Molecular , Farmacologia em Rede , Medicamentos de Ervas Chinesas/farmacologia , Cápsulas , Infarto Cerebral
6.
Curr Psychol ; : 1-13, 2022 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-36593906

RESUMO

The outbreak of COVID-19 has brought many challenges to youth development. During this specific period, adolescents have suffered from numerous behavioral problems, which will lead to more maladaptive consequences. It is necessary to explore several protective factors to prevent or reduce the occurrence of problem behaviors in adolescence. The current study combined school resources and self-control to evaluate the multiple protective effects on adolescents' problematic behaviors in a two-wave longitudinal study. A sample of 789 Chinese adolescents (Mage = 14.00 years, SD = 2.05, 418 boys) were recruited via the random cluster sampling method to participate in the survey. The results confirmed the assumptions about the multiple protective effects of school resources and self-control on adolescents' problem behaviors. Specifically, school resources could negatively predict IGD and victimization, and self-control mediated these associations. Moreover, one problematic behavior could also mediate the associations between self-control and another problematic behavior. This is the first study to focus on the multiple protective effects of positive factors on adolescents' problem behaviors during the post-pandemic period, which has made several contributions to the literature and practice.

7.
Zhongguo Zhong Yao Za Zhi ; 47(12): 3361-3371, 2022 Jun.
Artigo em Zh | MEDLINE | ID: mdl-35851130

RESUMO

A high performance liquid chromatography(HPLC) method was established to analyze the components in Shengjiang Powder(SJP) such as emodin and curcumin and explore its therapeutic effect on experimental autoimmune encephalomyelitis(EAE) mice. To be specific, HPLC was performed to determine the content of compounds in SJP such as emodin and curcumin. A total of 72 female SPF C57 BL/6 mice were randomized into control group(equivalent volume of ultrapure water, ig), model group(equivalent volume of ultrapure water, ig), low-, medium-, and high-dose SJP groups(SJP, ig), and positive control group(prednisone acetate, ig), 12 each group. EAE was induced in mice except the control group. Administration began from the first day after immunization. The general conditions, symptom score, and body weight of the mice were recorded. On the 21 st day, mouse brain tissues were separrated. Then hematoxylin-eosin(HE) staining and Luxol Fast Blue(LFB) staining were used to detect the pathological changes of brain tissues. Immunohistochemistry(IHC) was employed to determine the myelin basic protein(MBP) level, and Western blot the expression of occludin and claudin-5, as well as the levels of interleukin-6(IL-6) and proteins in the Janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3) pathway and their phosphorylation levels. The mRNA expression of IL-6, JAK2, and STAT3 was detected by real-time quantitative polymerase chain reaction(qPCR). Finally, molecular docking of six main active components in SJP, including emodin and curcumin, with IL-6, JAK2 and STAT3 was performed, and the binding affinity was evaluated. The results showed that the established HPLC method demonstrated high precision, reproducibility, stability, and high recovery of samples. Compared with the model group, SJP reduced the clinical symptom score and alleviate the inflammatory infiltration of brain white matter and demyelination of EAE mice. At the same time, SJP increased the expression of occludin and claudin-5, down-regulated the mRNA expression of IL-6, JAK2, and STAT3, as well as the levels of IL-6/JAK/STAT3 proteins and the phosphorylation levels, with significant difference. Molecular docking suggested that the six active components in SJP had high binding energy with IL-6, JAK2, and STAT3 proteins. The established HPLC method is simple, accurate, and highly sensitive, which can simultaneously determine the content of emodin and curcumin in SJP. SJP may alleviate the clinical symptoms of EAE by inhibiting IL-6/JAK2/STAT3 signaling pathway, protecting the blood-brain barrier, and relieving the inflammatory response and demyelinization of brain tissue.


Assuntos
Curcumina , Emodina , Encefalomielite Autoimune Experimental , Animais , Cromatografia Líquida de Alta Pressão , Claudina-5/metabolismo , Encefalomielite Autoimune Experimental/tratamento farmacológico , Encefalomielite Autoimune Experimental/genética , Feminino , Interleucina-6/genética , Interleucina-6/metabolismo , Janus Quinase 2/genética , Janus Quinase 2/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Simulação de Acoplamento Molecular , Ocludina/metabolismo , Pós , RNA Mensageiro , Reprodutibilidade dos Testes , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais , Água/metabolismo
8.
Proc Natl Acad Sci U S A ; 115(5): 1015-1020, 2018 01 30.
Artigo em Inglês | MEDLINE | ID: mdl-29339491

RESUMO

E-type cyclins (cyclins E1 and E2) are components of the core cell cycle machinery and are overexpressed in many human tumor types. E cyclins are thought to drive tumor cell proliferation by activating the cyclin-dependent kinase 2 (CDK2). The cyclin E1 gene represents the site of recurrent integration of the hepatitis B virus in the pathogenesis of hepatocellular carcinoma, and this event is associated with strong up-regulation of cyclin E1 expression. Regardless of the underlying mechanism of tumorigenesis, the majority of liver cancers overexpress E-type cyclins. Here we used conditional cyclin E knockout mice and a liver cancer model to test the requirement for the function of E cyclins in liver tumorigenesis. We show that a ubiquitous, global shutdown of E cyclins did not visibly affect postnatal development or physiology of adult mice. However, an acute ablation of E cyclins halted liver cancer progression. We demonstrated that also human liver cancer cells critically depend on E cyclins for proliferation. In contrast, we found that the function of the cyclin E catalytic partner, CDK2, is dispensable in liver cancer cells. We observed that E cyclins drive proliferation of tumor cells in a CDK2- and kinase-independent mechanism. Our study suggests that compounds which degrade or inhibit cyclin E might represent a highly selective therapeutic strategy for patients with liver cancer, as these compounds would selectively cripple proliferation of tumor cells, while sparing normal tissues.


Assuntos
Ciclina E/metabolismo , Neoplasias Hepáticas/metabolismo , Animais , Carcinogênese/genética , Carcinogênese/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Ciclina E/deficiência , Ciclina E/genética , Quinase 2 Dependente de Ciclina/metabolismo , Ciclinas/deficiência , Ciclinas/genética , Ciclinas/metabolismo , Progressão da Doença , Feminino , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas Experimentais/genética , Neoplasias Hepáticas Experimentais/metabolismo , Neoplasias Hepáticas Experimentais/patologia , Masculino , Camundongos , Camundongos Knockout , Proteínas Oncogênicas/deficiência , Proteínas Oncogênicas/genética , Proteínas Oncogênicas/metabolismo
9.
Cancer Sci ; 111(2): 489-501, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31854042

RESUMO

The NOTCH2 gene plays a role in the development of many tumors. Deltex E3 ubiquitin ligase 3 (DTX3) was identified as a novel E3 ligase for NOTCH2 and as a potential therapeutic target for esophageal cancer. However, whether DTX3 could regulate NOTCH2 to suppress the progression of esophageal carcinoma remains unknown. In our study, NOTCH2 had higher expression in human esophageal carcinoma cell lines compared to normal human esophageal epithelial cell line, and ablation of NOTCH2 suppressed the proliferation and migration of esophageal carcinoma cells. A novel E3 ligase for NOTCH2 was identified by yeast two-hybrid (Y2H) screening, and DTX3 promoted the ubiquitination and degradation of NOTCH2. Further study showed that DTX3 overexpression suppressed the proliferation and tumorigenicity of human oesophageal carcinoma cells. The analysis of tissue samples from patients revealed that the expression of NOTCH2 was high while the expression of DTX3 was low in esophageal cancer. Furthermore, the expression of DTX3 and NOTCH2 showed a significant negative correlation in human oesophageal cancer samples. Our study suggested that the DTX3-NOTCH2 axis plays an important role in the progression of esophageal cancer, and DTX3 acts as an anti-oncogene in esophageal carcinoma, potentially offering a therapeutic target for esophageal cancer.


Assuntos
Neoplasias Esofágicas/patologia , Receptor Notch2/química , Receptor Notch2/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Animais , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Progressão da Doença , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Camundongos , Invasividade Neoplásica , Transplante de Neoplasias , Proteólise , Transdução de Sinais , Ubiquitinação
10.
Zhongguo Zhong Yao Za Zhi ; 45(12): 2924-2931, 2020 Jun.
Artigo em Zh | MEDLINE | ID: mdl-32627468

RESUMO

According to traditional Chinese medicine, "spleen transport" is closely related to the metabolism of substance and energy. Studies have shown that Alzheimer's disease(AD) is a disease related to glucose and lipid metabolism and energy metabolism. The traditional Chinese medicine Jiangpi Recipe can improve the learning ability and memory of AD animal model. Sijunzi Decoction originated from Taiping Huimin Hefang Prescription is the basic prescription for strengthening and nourishing the spleen, with the effects of nourishing Qi and strengthening the spleen. In this experiment, human brain microvascular endothelial cells(HBMEC) and Sijunzi Decoction water extract(0.25, 0.5, 1 mg·L~(-1)) were pre-incubated for 2 h, and then Aß_(25-35) oligomers(final concentration 40 µmol·L~(-1)) was added for co-culture for 22 hours. The effect of Sijunzi Decoction on the activity of Aß_(25-35) oligomer injured cells and the expression of related proteins were investigated. Q-TOF-LC-MS was used first for principal component analysis of Sijunzi Decoction water extract. Then MTT assay was used to investigate the effect of Sijunzi Decoction water extract on the proliferation of HBMEC cells. Real-time fluorescence quantitative PCR(RT-qPCR) was employed to detect the mRNA expression of GLUT1, RAGE, and LRP1. The expression of Aß-related proteins across blood-brain barrier(RAGE, LRP1) was detected by Western blot. The results showed that 40 µmol·L~(-1) Aß_(25-35) oligomers could induce endothelial cell damage, reduce cell survival, increase expression of RAGE mRNA and RAGE protein, and reduce expression of GLUT1 mRNA, LRP1 mRNA, and LRP1 protein. Sijunzi Decoction water extract could reduce the Aß_(25-35) oligomer-induced cytotoxicity of HBMEC, decrease the expression of RAGE mRNA and RAGE protein, and increase the expression of GLUT1 mRNA, LRP1 mRNA and LRP1 protein. The results indicated that Sijunzi Decoction could reduce the injury of HBMEC cells induced by Aß_(25-35) oligomer, and regulate the transport-related proteins GLUT1, RAGE and LRP1, which might be the mechanism of regulating Aß_(25-35) transport across the blood-brain barrier.


Assuntos
Barreira Hematoencefálica , Medicamentos de Ervas Chinesas , Peptídeos beta-Amiloides , Animais , Células Endoteliais , Humanos
11.
Zhongguo Zhong Yao Za Zhi ; 45(18): 4429-4439, 2020 Sep.
Artigo em Zh | MEDLINE | ID: mdl-33164373

RESUMO

This paper was aimed to explore the potential pharmacodynamics effect of Euonymus alatus in the treatment of nephritis based on integrated chemomics and network biology. The chemical constituent database of E. alatus was constructed by consulting litera-ture and using online database. The chemical constituents were identified by UPLC-Q-TOF/HRMS~E and UNIFI software. On this basis, a series of comparisons, molecular docking studies and in-depth analysis of the chemical constituents and nephritis disease targets were carried out with use of network biology method, and the potential pharmacodynamic effect of E. alatus for the treatment of nephritis was investigated by reviewing the existing. In this study, 62 chemical constituents were collected in the database of chemical consti-tuents of E. alatus, and 24 chemical constituents were identified by mass spectrum. Subsequently, based on the network biology me-thod, 22 important chemical constituents and 5 key targets were obtained by reverse screening. Molecular docking study showed that a total of 11 chemical constituents such as quercetin, kaempferol, and catechinmay be the potential material basis for E. alatus in the treatment of nephritis. Starting with chemomics and using the technology of network biology, we established a network interaction model between drug components and disease targets in this study. Through the interaction between targets in complex networks, we can find the key targets easily and quickly. By docking the key targets with small drug molecules, we can screen out the potential pharmacodynamic components, providing a reference for the follow-up study of active ingredients.


Assuntos
Euonymus , Nefrite , Seguimentos , Humanos , Simulação de Acoplamento Molecular , Quercetina
12.
Zhongguo Zhong Yao Za Zhi ; 45(12): 2772-2783, 2020 Jun.
Artigo em Zh | MEDLINE | ID: mdl-32627450

RESUMO

Periplocae Cortex is a traditional Chinese medicine in China, which is mainly produced in northeast China, north China, northwest China, southwest China. In recent years, the increasing in-depth research resulted in the discovery of anti-tumor and cardiac pharmacological activities of Periplocae Cortex, which has broad application prospects. On the basis of summarizing chemical components and pharmacological effects, combined with the theoretical system of Q-marker, the quality control components of Periplocae Cortex were predicted from the aspects of the correlation between chemical composition and traditional medicinal properties, traditional efficacy, and new clinical use, plasma composition, measurable composition, storage time by analyzing literature. Among the components, periplocoside, periplocin, periplogenin, 4-methoxy salicylaldehyde showed significant activity, which provides a scientific basis for quality evaluation of Periplocae Cortex.


Assuntos
Medicamentos de Ervas Chinesas/análise , Medicina Tradicional Chinesa , Biomarcadores , China , Controle de Qualidade
13.
Carcinogenesis ; 40(10): 1229-1239, 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31157866

RESUMO

1p/19q codeletion, which leads to the abnormal expression of 1p19q genes in oligodendroglioma, is associated with chemosensitivity and favorable prognosis. Here, we aimed to explore the clinical implications of 1p19q gene expression in 1p/19q non-codel gliomas. We analyzed expression of 1p19q genes in 668 1p/19q non-codel gliomas obtained from The Cancer Genome Atlas (n = 447) and the Chinese Glioma Genome Atlas (n = 221) for training and validation, respectively. The expression of 1p19q genes was significantly correlated with the clinicopathological features and overall survival of 1p/19q non-codel gliomas. Then, we derived a risk signature of 25 selected 1p19q genes that not only had prognosis value in total 1p/19q non-codel gliomas but also had prognosis value in stratified gliomas. The prognosis value of the risk signature was superior than known clinicopathological features in 1p/19q non-codel gliomas and was also highly associated with the following features: loss of CDKN2A/B copy number in mutant-IDH-astrocytoma; telomerase reverse transcriptase (TERT) promoter mutation, combined chromosome 7 gain/chromosome 10 loss and epidermal growth factor receptor amplification in wild-type-IDH-astrocytoma; classical and mesenchymal subtypes in glioblastoma. Furthermore, genes enriched in the biological processes of cell division, extracellular matrix, angiogenesis significantly correlated to the signature risk score, and this is also supported by the immunohistochemistry and cell biology experiments. In conclusion, the expression profile of 1p19q genes is highly associated with the malignancy and prognosis of 1p/19q non-codel gliomas. A 25-1p19q-gene signature has powerfully predictive value for both malignant molecular pathological features and prognosis across distinct subgroups of 1p/19q non-codel gliomas.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias Encefálicas/patologia , Deleção Cromossômica , Cromossomos Humanos Par 19/genética , Regulação Neoplásica da Expressão Gênica , Glioma/patologia , Mutação , Adulto , Idoso , Idoso de 80 Anos ou mais , Apoptose , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/cirurgia , Movimento Celular , Proliferação de Células , Seguimentos , Glioma/genética , Glioma/cirurgia , Humanos , Pessoa de Meia-Idade , Prognóstico , RNA-Seq , Taxa de Sobrevida , Transcriptoma , Células Tumorais Cultivadas , Adulto Jovem
14.
Mod Pathol ; 32(1): 4-15, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30291347

RESUMO

The methylation status of the promoter of MGMT gene is a crucial factor influencing clinical decision-making in patients with gliomas. MGMT pyrosequencing results are often dichotomized by a cut-off value based on an average of several tested CpGs. However, this method frequently results in a "gray zone", representing a dilemma for physicians. We therefore propose a novel analytical model for MGMT methylation pyrosequencing. MGMT CpG heterogeneity was investigated in 213 glioma patients in two tested cohorts: cohort A in which CpGs 75-82 were tested and cohort B in which CpGs 72-78 were tested. The predictive performances of the novel and traditional averaging models were compared in 135 patients who received temozolomide using receiver operating characteristic curves and Kaplan-Meier curves, and in patients stratified according to isocitrate dehydrogenase gene mutation status. The results were validated in an independent cohort of 65 consecutive patients with high-grade gliomas from the Chinese Glioma Genome Atlas database. Heterogeneity of MGMT promoter CpG methylation level was observed in most gliomas. The optimal cut-off value for each individual CpG varied from 4-16%. The current analysis defined MGMT promoter methylation as occurring when at least three CpGs exceeded their respective cut-off values. This novel analysis could accurately predict the prognosis of patients in the methylation "gray zone" according to the standard averaging method, and improved the area under the curves from 0.67, 0.76, and 0.67 to 0.70, 0.84, and 0.72 in cohorts A, B, and the validation cohort, respectively, demonstrating superiority of this analytical method in all three cohorts. Furthermore, the advantages of the novel analysis were retained regardless of WHO grade and isocitrate dehydrogenase gene mutation status. In conclusion, this novel analytical model offers an improved clinical predictive performance for MGMT pyrosequencing results and is suitable for clinical use in patients with gliomas.


Assuntos
Neoplasias Encefálicas/genética , Metilação de DNA , Metilases de Modificação do DNA/genética , Enzimas Reparadoras do DNA/genética , Glioma/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Proteínas Supressoras de Tumor/genética , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
16.
Cancer Cell Int ; 19: 155, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31171919

RESUMO

BACKGROUND: Abnormal expression of the eukaryotic initiation factor 3 (eIF3) subunits plays critical roles in tumorigenesis and progression, and also has potential prognostic value in cancers. However, the expression and clinical implications of eIF3 subunits in glioma remain unknown. METHODS: Expression data of eIF3 for patients with gliomas were obtained from the Chinese Glioma Genome Atlas (CGGA) (n = 272) and The Cancer Genome Atlas (TCGA) (n = 595). Cox regression, the receiver operating characteristic (ROC) curves and Kaplan-Meier analysis were used to study the prognostic value. Gene oncology (GO) and gene set enrichment analysis (GSEA) were utilized for functional prediction. RESULTS: In both the CGGA and TCGA datasets, the expression levels of eIF3d, eIF3e, eIF3f, eIF3h and eIF3l highly were associated with the IDH mutant status of gliomas. The expression of eIF3b, eIF3i, eIF3k and eIF3m was increased with the tumor grade, and was associated with poorer overall survival [All Hazard ratio (HR) > 1 and P < 0.05]. By contrast, the expression of eIF3a and eIF3l was decreased in higher grade gliomas and was associated with better overall survival (Both HR < 1 and P < 0.05). Importantly, the expression of eIF3i (located on chromosome 1p) and eIF3k (Located on chromosome 19q) were the two highest risk factors in both the CGGA [eIF3i HR = 2.068 (1.425-3.000); eIF3k HR = 1.737 (1.166-2.588)] and TCGA [eIF3i HR = 1.841 (1.642-2.064); eIF3k HR = 1.521 (1.340-1.726)] databases. Among eIF3i, eIF3k alone or in combination, the expression of eIF3i was the more robust in stratifying the survival of glioma in various pathological subgroups. The expression of eIF3i was an independent prognostic factor in IDH-mutant lower grade glioma (LGG) and could also predict the 1p/19q codeletion status of IDH-mutant LGG. Finally, GO and GSEA analysis showed that the elevated expression of eIF3i was significantly correlated with the biological processes of cell proliferation, mRNA processing, translation, T cell receptor signaling, NF-κB signaling and others. CONCLUSIONS: Our study reveals the expression alterations during glioma progression, and highlights the prognostic value of eIF3i in IDH-mutant LGG.

17.
Zhongguo Dang Dai Er Ke Za Zhi ; 21(9): 876-880, 2019 Sep.
Artigo em Zh | MEDLINE | ID: mdl-31506145

RESUMO

OBJECTIVE: To study the correlation of Mycoplasma pneumoniae DNA (MP-DNA) replication level in throat swab and bronchoalveolar lavage fluid (BALF) with disease severity in children with severe Mycoplasma pneumoniae pneumonia (SMPP). METHODS: A total of 44 children with SMPP who underwent bronchoalveolar lavage were enrolled as subjects. The serum levels of cytokines and MP-DNA replication times in throat swab were measured in the acute stage and the recovery stage, and the levels of interleukin (IL)-8 and MP-DNA replication times in BALF were measured in the acute stage. According to whether mechanical ventilation was needed for respiratory failure, the children were divided into a mechanical ventilation group (n=19) and a non-mechanical ventilation group (n=25), and the two groups were compared in MP-DNA replication times in BALF. RESULTS: For the children with SMPP, serum levels of C-reactive protein, erythrocyte sedimentation rate, lactate dehydrogenase, IL-1, IL-6, IL-8, and IL-18 in the acute stage were significantly higher than those in the recovery stage (P<0.05). In the acute stage, MP-DNA replication times in throat swab were positively correlated with those in BALF (r=0.613, P<0.05), and MP-DNA replication times in BALF were positively correlated with IL-18 levels in peripheral blood and BALF (r=0.613 and 0.41 respectively, P<0.05). Compared with the non-mechanical ventilation group, the mechanical ventilation group had significantly higher MP-DNA replication times in BALF, a significantly longer duration of systemic hormone treatment, significantly higher serum levels of lactate dehydrogenase and IL-18, and significantly higher white blood cell count and IL-18 level in BALF (P<0.05). CONCLUSIONS: In children with SMPP, MP-DNA replication level in throat swab and BALF can be used as a reference index for the assessment of disease severity.


Assuntos
Mycoplasma pneumoniae , Pneumonia por Mycoplasma , Líquido da Lavagem Broncoalveolar , Criança , Citocinas , Replicação do DNA , DNA Bacteriano , Humanos
18.
J Cell Mol Med ; 22(3): 2023-2027, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29314715

RESUMO

Both microscopic and endoscopic transsphenoidal surgery are effective approaches for nonfunctioning pituitary adenomas. The issue on the comparison of their efficacy and safety remains inconsistent. A thorough search of the literatures (PubMed, EMBASE, MEDLINE) were performed up to March 2017. Studies reporting outcomes of microscopic or endoscopic transsphenoidal surgery on nonfunctioning pituitary adenomas were included. A meta-analysis was performed focusing on the early stage and long term outcomes. The final search yielded 19 eligible studies enrolling 3847 patients, 389 of them underwent microscopic approach and 3458 of them with endoscopic approach. As to the early stage outcomes, the rate of gross tumor resection was significantly higher in the endoscopic group than that in microscopic group (73% versus 60%, P < 0.001). Meanwhile, endoscopic approach showed priority over microscopy on postoperative hypopituitarism (63% versus 65%, P < 0.001) and CSF leakage (3% versus 7%, P < 0.001). For the long term outcomes, the rate of visual improvement was significant higher in the endoscopic group than that in microscopic group (77% versus 50%, P < 0.001). However, there was no significant difference between the groups regarding the rate of permanent diabetic insipidus and meningitis. The endoscopic approach may be associated with higher rate of gross tumor movement and lower risk of postoperatively complications for treating nonfunctioning pituitary adenoma, when compared with microscopic approach. However, the confidence was shorted due to limited high quality evidence (largely randomized and controlled studies).


Assuntos
Adenoma/cirurgia , Diabetes Insípido/diagnóstico , Endoscopia/métodos , Hipopituitarismo/diagnóstico , Meningite/diagnóstico , Neoplasias Hipofisárias/cirurgia , Complicações Pós-Operatórias/diagnóstico , Adenoma/patologia , Diabetes Insípido/etiologia , Diabetes Insípido/fisiopatologia , Feminino , Humanos , Hipopituitarismo/etiologia , Hipopituitarismo/fisiopatologia , Masculino , Meningite/etiologia , Meningite/fisiopatologia , Pessoa de Meia-Idade , Neoplasias Hipofisárias/patologia , Complicações Pós-Operatórias/fisiopatologia , Osso Esfenoide/cirurgia , Resultado do Tratamento , Acuidade Visual
19.
Zhonghua Nan Ke Xue ; 23(4): 309-314, 2017 Apr.
Artigo em Zh | MEDLINE | ID: mdl-29714414

RESUMO

OBJECTIVE: To investigate the expressions of JNK and p-JNK in advanced prostate cancer (PCa) and benign prostatic hyperplasia (BPH) and their implications. METHODS: Using immunohistochemistry, we detected the expressions of JNK and p-JNK proteins in 40 cases of paraffin wax-embedded PCa and 21 cases of BPH tissues and analyzed their relationships with advanced PCa and BPH as well as with the pathologic features of advanced PCa. RESULTS: Statistically significant differences were not found in the positive expression rate of the JNK protein between BPH and PCa (42.86% vs 52.50%, P>0.05), non-metastatic and metastatic PCa (53.85% vs 51.85%, P >0.05), Gleason ≤7 and Gleason >7 (58.82% vs 47.82%, P >0.05), PSA ≤20 µg/L and PSA >20 µg/L (57.14% vs 51.52%, P >0.05), or survival >5 yr and survival ≤5 yr (60.00% vs 45.00%, P >0.05), nor in the expression level of p-JNK between BPH and PCa (33.33% vs 35.00%, P >0.05), non-metastatic and metastatic PCa (30.77% vs 37.03%, P >0.05), Gleason ≤7 and Gleason >7 (35.29% vs 34.78%, P >0.05), or PSA ≤20 µg/L and PSA >20 µg/L (43.75% vs 10.93%, P >0.05). However, the expression of p-JNK was significantly higher in the survival >5 yr than in the survival ≤5 yr group of the PCa patients (50.00% vs 20.00%, P <0.05). CONCLUSIONS: PCa patients with highly expressed p-JNK have a longer survival time and the high positive rate of p-JNK is associated with the prognosis of PCa.


Assuntos
Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Proteínas de Neoplasias/metabolismo , Hiperplasia Prostática/enzimologia , Neoplasias da Próstata/enzimologia , Humanos , Imuno-Histoquímica , Masculino , Gradação de Tumores , Prognóstico , Antígeno Prostático Específico/metabolismo , Hiperplasia Prostática/mortalidade , Hiperplasia Prostática/patologia , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/patologia
20.
Zhonghua Nan Ke Xue ; 23(5): 406-411, 2017 May.
Artigo em Zh | MEDLINE | ID: mdl-29717829

RESUMO

OBJECTIVE: To investigate the expressions of extracellular signal-regulated kinase (ERK) and p-ERK in benign and malignant prostate tissues, and whether it can be used as a marker for the prognosis of advanced prostate cancer (PCa). METHODS: Using immunohistochemical Envision, we detected the expressions of ERK1/2 and p-ERK1/2 in 20 cases of benign prostatic hyperplasia (BPH) and 40 cases of advanced PCa and analyzed their correlation with PCa metastasis, Gleason score, PSA level, and prognosis. RESULTS: The expression of ERK1/2 was remarkably higher in the advanced PCa than in the BPH cases (82.5% vs 55%, P<0.05), which was not associated with cancer metastasis, Gleason score, PSA level, or survival time of the patients with advanced PCa, and so was that of p-ERK1/2 (75.0% vs 35%, P<0.05), which was not associated with the Gleason score or PSA level of the PCa patients, either. The expression rates of p-ERK in the metastasis, non-metastasis, survival >5 yr, and survival ≤ 5 yr groups were 61.9%, 89.5%, 57.9%, and 90.5%, respectively, with statistically significant differences among these groups (P<0.05). CONCLUSIONS: ERK1/2 and p-ERK1/2 proteins are highly expressed in advanced PCa and p-ERK1/2 is associated with the metastasis and prognosis of advanced PCa.


Assuntos
Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Próstata/enzimologia , Hiperplasia Prostática/enzimologia , Neoplasias da Próstata/enzimologia , Biomarcadores Tumorais/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Humanos , Masculino , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Gradação de Tumores , Metástase Neoplásica , Prognóstico , Antígeno Prostático Específico/metabolismo , Hiperplasia Prostática/patologia , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/patologia
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