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1.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 52(5): 832-838, 2021 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-34622601

RESUMO

Objective: To study the distributional characteristics of allergens in children with allergic diseases in Shaanxi province. Methods: A total of 4 622 children diagnosed with allergic diseases in the Asthma Center, Department of Pediatrics, Xijing Hospital from March 2015 to February 2019 were selected. Serum allergen-specific immunoglobulin E (sIgE) of 19 common kinds of allergens were examined with enzyme-linked immunosorbent assay (ELISA). The children were divided into different groups according to sex, age and geographical regions, and the distributional characteristics of allergens of the different groups were compared. Results: The overall positive rate for the 19 allergens of the 4 622 children was 62.8%. The ranking of the positive rates for individual allergens from high to low were as follows: 24.2% for milk, 18.0% for mold mix, 16.7% for dog dander, 16.4% for house dust mite, 11.7% for cat dander, 10.7% for cashew, 10.6% for weed pollen, 8.8% for egg white, 7.8% for house dust, 7.7% for tree pollen, 5.6% for amaranth, 4.9% for mulberry tree, 3.6% for mango, 3.2% for beef, 2.8% for cockroach, 2.1% for crab, 1.5% for shrimp, 0.8% for pineapple, and 0.3% for shellfish. Analysis based on sex showed that the allergen positive rates in boys were higher than those in girls. Analysis by age difference showed that generally the positive rates for inhaled allergens increased along with the increase in patient age, while the positive rates for ingested allergens decreased along with the increase in patient age. Analysis by geographical regions showed that the positive rate of house dust mite in the patients from the southern part of Shaanxi, the positive rate of weed pollen in the patients from the northern part of Shaanxi and the positive rates of milk and egg white in the patients from the central part of Shaanxi were higher than those in other areas. The cluster analysis and correlation analysis showed that the 19 allergens could be roughly divided into 4 categories. There were moderate correlations among tree pollen, mulberry tree and amaranth. There were moderate correlations among mulberry tree, mango and amaranth. There was moderate correlation between shrimp and crab, and there were mild or weak correlations among most of the other allergens. Conclusion: Among the 4 622 children with allergic diseases in Shaanxi Province who were treated in the Asthma Center, Department of Pediatrics, Xijing Hospital, male patients showed higher sensitivity to allergens. The positive rates of inhaled allergens increased, while the positive rates of ingested allergens decreased with increase in patient age. There were regional differences in the distribution of allergens. Some allergens were correlated with each other, which may be related to cross-reaction.


Assuntos
Asma , Hipersensibilidade , Alérgenos , Animais , Asma/epidemiologia , Gatos , Bovinos , Criança , Cães , Poeira , Humanos , Imunoglobulina E , Masculino
4.
Diabetes Res Clin Pract ; 178: 108987, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34329693

RESUMO

AIMS: Tsukushi, a newly identified hepatokine, has been recently characterized as a potent modifier in lipid metabolism and energy homeostasis, but the role of Tsukushi in diabetes remains almost unknown. We detected for the first time the serum Tsukushi levels in newly diagnosed type 2 diabetes, exploring the relationship between Tsukushi and various metabolic parameters. METHODS: A total of 172 participants were recruited, including 86 patients with newly diagnosed type 2 diabetes and 86 subjects with normal glucose tolerance according to oral glucose tolerance test. Serum Tsukushi was measured by ELISA. The insulin resistance, pancreas ß-cell function and insulin sensitivity were determined by homeostasis model assessment (HOMA-IR, HOMA-ß), Stumvoll insulin sensitivity index (ISIstumvoll) and Stumvoll metabolic clearance rate (MCRstumvoll). RESULTS: Serum Tsukushi was significantly higher in type 2 diabetes than in normal glucose tolerance [1.22(0.86,1.74) vs 0.8(0.5,1.38) ng/mL; P < 0.001]. Multiple regression analysis showed that BMI, 2-h post-OGTT glucose and TC were independently related factors influencing Tsukushi. Logistic regression analyses demonstrated that Tsukushi was associated with higher risk of type 2 diabetes independently. CONCLUSIONS: Circulating Tsukushi levels significantly increase in patients with type 2 diabetes, which suggest that Tsukushi may play a role in type 2 diabetes pathogenesis.


Assuntos
Diabetes Mellitus Tipo 2 , Resistência à Insulina , Células Secretoras de Insulina , Glicemia , Diabetes Mellitus Tipo 2/diagnóstico , Glucose , Teste de Tolerância a Glucose , Humanos , Insulina
5.
Appl Environ Microbiol ; 87(14): e0022721, 2021 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-33962978

RESUMO

The families of copper-containing membrane-bound monooxygenases (CuMMOs) and soluble di-iron monooxygenases (SDIMOs) are involved not only in methane oxidation but also in short-chain alkane oxidation. Here, we describe Rhodococcus sp. strain ZPP, a bacterium able to grow with ethane or propane as the sole carbon and energy source, and report on the horizontal gene transfer (HGT) of actinobacterial hydrocarbon monooxygenases (HMOs) of the CuMMO family and the sMMO (soluble methane monooxygenase)-like SDIMO in the genus Rhodococcus. The key function of HMO in strain ZPP for propane oxidation was verified by allylthiourea inhibition. The HMO genes (designated hmoCAB) and those encoding sMMO-like SDIMO (designated smoXYB1C1Z) are located on a linear megaplasmid (pRZP1) of strain ZPP. Comparative genomic analysis of similar plasmids indicated the mobility of these plasmids within the genus Rhodococcus. The plasmid pRZP1 in strain ZPP could be conjugatively transferred to a recipient Rhodococcus erythropolis strain in a mating experiment and showed similar ethane- and propane-consuming activities. Finally, our findings demonstrate that the horizontal transfer of plasmid-based CuMMO and SDIMO genes confers the ability to use ethane and propane on the recipient. IMPORTANCE CuMMOs and SDIMOs initiate the aerobic oxidation of alkanes in bacteria. Here, the supposition that horizontally transferred plasmid-based CuMMO and SDIMO genes confer on the recipient similar abilities to use ethane and propane was proposed and confirmed in Rhodococcus. This study is a living example of HGT of CuMMOs and SDIMOs and outlines the plasmid-borne properties responsible for gaseous alkane degradation. Our results indicate that plasmids can support the rapid evolution of enzyme-mediated biogeochemical processes.


Assuntos
Proteínas de Bactérias/genética , Oxigenases de Função Mista/genética , Rhodococcus/genética , Etano/metabolismo , Transferência Genética Horizontal , Genes Bacterianos , Oxirredução , Plasmídeos , Propano/metabolismo , Rhodococcus/metabolismo
6.
Antonie Van Leeuwenhoek ; 114(8): 1205-1212, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33973093

RESUMO

The cell of a rod-shaped bacterium is composed of a cylinder and two hemispherical poles. In recent decades, the molecular mechanism of morphogenesis in rod-shaped bacteria has received extensive research. However, most works have focused on the morphogenesis of cylinders, and the morphogenesis of the hemispherical poles remains unclear. In the past, the pole of bacterial cell wall was considered as a rigid hemispherical structure. However, our work indicated that the pole in the isolated sacculi from Bacillus subtilis was a flat structure instead of a hemisphere form. Further works showed that internal pressure was responsible for shaping the hemispherical poles, indicating an elastic nature of the cell wall in poles. In addition, we found that the internal pressure was able to transform septa into hemispherical shape which is similar to normal poles. Based on our work, we proposed a model for the internal pressure-induced formation of hemispherical poles in B. subtilis, and this work may provide new clues into basic knowledge of the morphogenesis of rod-shaped bacteria.


Assuntos
Bacillus subtilis , Parede Celular , Bacillus subtilis/genética , Proteínas de Bactérias , Morfogênese
7.
Med Sci Monit ; 27: e929389, 2021 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-33714972

RESUMO

BACKGROUND Accumulated evidence has suggested that hydrogen sulfide (H2S) has a role in bone formation and bone tissue regeneration. However, it is unknown whether the H2S content is associated with bone mineral density (BMD) in patients with osteopenia/osteoporosis. MATERIAL AND METHODS In the present study, we aimed to explore the changes of serum H2S in osteopenia and osteoporosis patients. We analyzed femur expression of cystathionine ß synthase (CBS), cystathionine γ lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (3-MST), which are key enzymes for generating H2S. RESULTS Sixteen (16%) patients had osteopenia, 9 (9%) had osteoporosis, and 75 (75%) had normal BMD. In comparison with patients with normal BMD (controls), the serum levels of H2S were unexpectedly increased in patients with osteopenia and osteoporosis. This increase was much higher in patients with osteoporosis than in those with osteopenia. Serum H2S levels were negatively correlated with femoral BMD, but not lumbar BMD. Interestingly, the expression of CBS and CSE were downregulated in femur tissues in patients with osteoporosis, whereas the expression of 3-MST remained unchanged. Serum phosphorus levels, alkaline phosphatase, hemoglobin, and triglycerides were found to be closely associated with CBS and CSE scores in femur tissues. CONCLUSIONS Serum H2S levels and femur CBS and CSE expression may be involved in osteoporosis pathogenesis.


Assuntos
Fêmur/metabolismo , Sulfeto de Hidrogênio/análise , Osteoporose/metabolismo , Idoso , Idoso de 80 Anos ou mais , Densidade Óssea/efeitos dos fármacos , Densidade Óssea/fisiologia , Doenças Ósseas Metabólicas/sangue , Doenças Ósseas Metabólicas/metabolismo , China , Cistationina beta-Sintase/análise , Cistationina gama-Liase/análise , Feminino , Fêmur/fisiologia , Humanos , Sulfeto de Hidrogênio/sangue , Masculino , Pessoa de Meia-Idade , Osteoporose/sangue , Sulfurtransferases/análise
8.
Nat Prod Bioprospect ; 11(1): 81-86, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33098068

RESUMO

Four new limonoids, toonayunnanaes F - I (1 - 4), and six known compounds (5 - 10) were isolated from the barks of Toona ciliata. Their structures were elucidated by thoroughly analyzing of NMR and HRMS data, and single-crystal X-ray diffraction of 1. The oxetane ring moiety in 1 was rare in limonoids and other natural products. Compound 1 showed nitric oxide (NO) inhibitory effect with an IC50 38.45 ± 0.41 µM in lipopolysaccharide (LPS)-activated RAW 264.7 macrophages.

9.
Phytochem Anal ; 32(3): 308-317, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-32744421

RESUMO

INTRODUCTION: Melia toosendan Sieb. et Zucc. has been used as a Chinese folk medicine for roundworm treatment since ancient times. Many diverse limonoids have been isolated from Meliaceae plants, but it remains difficult to isolate and identify other limonoids because of their small natural concentrations. OBJECTIVE: This study was performed to overcome the difficulties associated with fast and accurate identification of limonoids and establish a reliable and sensitive method for the analysis of minor limonoids in M. toosendan fruits. METHODS: An efficient strategy for enrichment, detection, and identification of minor limonoids from M. toosendan fruits using solid-phase extraction with high-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (SPE-HPLC-Q-TOF-MS/MS) was developed herein. RESULTS: Characteristic fragmentations and fragmentation ions containing trichilin-, nimbin-, and vilasinin-class limonoid skeletons were initially studied, and characteristic diagnostic ions involved retro Diels-Alder (RDA) reactions or homolytic cleavages, which were used to identify minor limonoids. In total, 13 limonoids, including four new ones, were identified. CONCLUSION: This is the first report on the analysis of M. toosendan fruits to identify limonoids. This novel analysis method may stimulate further research regarding the identification of limonoids in other plant species.


Assuntos
Limoninas , Melia , Cromatografia Líquida , Frutas , Extração em Fase Sólida , Espectrometria de Massas em Tandem
10.
Cancer Commun (Lond) ; 40(12): 721-737, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33038291

RESUMO

BACKGROUND: Epigenetic regulation plays an important role in the development and progression of nasopharyngeal carcinoma (NPC). However, the epigenetic mechanisms underlying NPC metastasis remains poorly understood. We aimed to find functional genes which regulate the metastasis of NPC and identify therapeutic targets for NPC treatment. METHODS: Bisulfite pyrosequencing was used to analyze zinc finger protein 582 (ZNF582) methylation in NPC tissues and cell lines. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blotting were used to determine the expression of ZNF582. In vitro and in vivo experiments were performed to evaluate the biological function of ZNF582 in NPC. ZNF582-targeting genes were identified by chromatin immunoprecipitation sequencing (ChIP-seq) and were confirmed by ChIP-qPCR and luciferase assay. RESULTS: ZNF582 promoter was hypermethylated in NPC, and both the mRNA and protein levels of ZNF582 were down-regulated in NPC tissues and cell lines. The restoration of ZNF582 inhibited NPC migration, invasion, and metastasis, while the knockdown of ZNF582 promoted NPC migration, invasion, and metastasis in vitro and in vivo. ZNF582 directly regulated the transcription and expression of adhesion molecules Nectin-3 and NRXN3. Both Nectin-3 and NRXN3 were identified as functional targets of ZNF582, and the restoration or abrogation of these genes reversed the tumor suppressor effect of ZNF582 in NPC metastasis. CONCLUSIONS: ZNF582 acts as a tumor suppressor gene in NPC by regulating the transcription and expression of adhesion molecules Nectin-3 and NRXN3, which may provide novel therapeutic targets for NPC treatment.


Assuntos
Metilação de DNA , Fatores de Transcrição Kruppel-Like/genética , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Nectinas/genética , Proteínas do Tecido Nervoso/genética , Linhagem Celular Tumoral , Epigênese Genética , Células HEK293 , Humanos , Carcinoma Nasofaríngeo/genética , Neoplasias Nasofaríngeas/genética , Regiões Promotoras Genéticas
11.
Cancer Manag Res ; 12: 5903-5907, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32765091

RESUMO

Objective: This study investigates the effect of the standardized management of cancer pain on patients with bone metastasis of lung cancer in China. Patients and Methods: A total of 123 patients with bone metastasis of lung cancer were selected from the Respiratory Department of the Affiliated Hospital of North China University of Science and Technology. Among these patients, 62 patients who had not received standardized management of cancer pain from March 12, 2018, to September 11, 2018, were selected as the control group. In contrast, 61 patients who had received the standardized management of cancer pain from September 12, 2018, to March 11, 2019, were selected as the observation group. The former cohort accepted the conventional management of cancer pain, while the latter accepted the strict, standardized management of cancer pain. The demographic statistics, disease characteristics, and painkiller application of patients in these two groups were analyzed. Then, the analgesic effect and level of satisfaction were compared between these two groups. Results: No significant differences were noticed between these two groups in terms of age, gender, smoking status, type of pathology, education level, previous treatment, and the Eastern Cooperative Oncology Group score, as well as other demographic and disease characteristics. As for the use of painkillers, opioid analgesics accounted for a higher proportion in the observation group than in the control group. Compared with the control group, pain improvement and patient satisfaction after analgesic treatment were significantly higher in the observation group (p < 0.05). Conclusion: The standardized management of cancer pain can considerably alleviate the pain of patients with bone metastasis of lung cancer and improve their quality of life. Furthermore, this type of management can increase satisfaction.

12.
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
13.
Oncogene ; 39(34): 5616-5632, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32661324

RESUMO

Increasing evidence indicates that long non-coding RNAs (lncRNAs) play vital roles in the tumorigenesis and progression of cancers. However, the functions and regulatory mechanisms of lncRNAs in nasopharyngeal carcinoma (NPC) are still largely unknown. Our previous lncRNA expression profiles identified that LINC01503 was overexpressed in NPC. Here, we verified that LINC01503 was highly expressed in NPC and correlated with poor prognosis. LINC01503 promoted NPC cell proliferation, migration, and invasion in vitro, and facilitated tumor growth and metastasis in vivo. Mechanistically, LINC01503 recruited splicing factor proline-and glutamine-rich (SFPQ) to activate Fos like 1 (FOSL1) transcription, and ectopic expression of FOSL1 reversed the suppressive effect of LINC01503 knockdown on NPC progression. Moreover, androgen receptor (AR)-mediated transcription activation was responsible for the overexpression of LINC01503, and AR ligand-dependent cell growth, migration, and invasion in NPC cells. Taken together, our findings reveal that AR-induced LINC01503 can promote NPC progression through the SFPQ-FOSL1 axis, which represents a novel prognostic biomarker and therapeutic target for NPC patients.


Assuntos
Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Carcinoma Nasofaríngeo/genética , Neoplasias Nasofaríngeas/genética , Fator de Processamento Associado a PTB/genética , Proteínas Proto-Oncogênicas c-fos/genética , RNA Longo não Codificante/genética , Receptores Androgênicos/genética , Animais , Linhagem Celular , Linhagem Celular Tumoral , Células HEK293 , Humanos , Estimativa de Kaplan-Meier , Metástase Linfática , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Carcinoma Nasofaríngeo/metabolismo , Carcinoma Nasofaríngeo/terapia , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/terapia , Fator de Processamento Associado a PTB/metabolismo , Proteínas Proto-Oncogênicas c-fos/metabolismo , Interferência de RNA , Receptores Androgênicos/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto/métodos
14.
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
15.
J Hematol Oncol ; 13(1): 22, 2020 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-32188475

RESUMO

Methylation of RNA and DNA, notably in the forms of N6-methyladenosine (m6A) and 5-methylcytosine (5mC) respectively, plays crucial roles in diverse biological processes. Currently, there is a lack of knowledge regarding the cross-talk between m6A and 5mC regulators. Thus, we systematically performed a pan-cancer genomic analysis by depicting the molecular correlations between m6A and 5mC regulators across ~ 11,000 subjects representing 33 cancer types. For the first time, we identified cross-talk between m6A and 5mC methylation at the multiomic level. Then, we further established m6A/5mC epigenetic module eigengenes by combining hub m6A/5mC regulators and informed a comprehensive epigenetic state. The model reflected status of the tumor-immune-stromal microenvironment and was able to predict patient survival in the majority of cancer types. Our results lay a solid foundation for epigenetic regulation in human cancer and pave a new road for related therapeutic targets.


Assuntos
5-Metilcitosina/metabolismo , Adenosina/análogos & derivados , Epigênese Genética , Neoplasias/genética , 5-Metilcitosina/imunologia , Adenosina/genética , Adenosina/imunologia , Metilação de DNA , Redes Reguladoras de Genes , Genômica , Humanos , Neoplasias/diagnóstico , Neoplasias/imunologia , Prognóstico , Microambiente Tumoral
16.
Med Sci Monit ; 26: e920394, 2020 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-32170053

RESUMO

BACKGROUND Oxidative stress and myocardial apoptosis are features of doxorubicin-induced cardiac toxicity that can result in cardiac dysfunction. Previous studies showed that microRNA-143 (miR-143) was expressed in the myocardium and had a role in cardiac function. This study aimed to investigate the effects and possible molecular mechanisms of miR-143 on oxidative stress and myocardial cell apoptosis in a mouse model of doxorubicin-induced cardiac toxicity. MATERIAL AND METHODS Mice underwent intraperitoneal injection of doxorubicin (15 mg/kg) daily for eight days to develop the mouse model of doxorubicin-induced cardiac toxicity. Four days before doxorubicin administration, a group of mice was pretreated daily with a miR-143 antagonist (25 mg/kg/day) for four consecutive days by tail vein injection. The study included the use of a miR-143 antagomir, or anti-microRNA, an oligonucleotide that silenced endogenous microRNA (miR), and an agomir to miR-143, and also the AKT inhibitor, MK2206. Quantitative real-time polymerase chain reaction (qRT-PCR) and immunoblot analysis were used to measure mRNA and protein expression, respectively. RESULTS Doxorubicin treatment increased the expression of miR-143, which was reduced by the miR-143 antagomir. Overexpression of miR-143 increased doxorubicin-induced myocardial apoptosis and oxidative stress. The use of the miR-143 antagomir significantly activated protein kinase B (PKB) and AKT, which were reduced in the presence of the AKT inhibitor, MK2206. However, the use of the miR-143 antagomir further down-regulated AKT phosphorylation following doxorubicin treatment and increased AKT activation. CONCLUSIONS In a mouse model of doxorubicin-induced cardiac toxicity, miR-143 increased oxidative stress and myocardial cell apoptosis following doxorubicin treatment by inhibiting AKT.


Assuntos
Cardiotoxicidade/genética , Doxorrubicina/toxicidade , MicroRNAs/metabolismo , Estresse Oxidativo/genética , Animais , Antagomirs/administração & dosagem , Apoptose/efeitos dos fármacos , Apoptose/genética , Cardiotoxicidade/etiologia , Linhagem Celular , Modelos Animais de Doenças , Coração/efeitos dos fármacos , Compostos Heterocíclicos com 3 Anéis/administração & dosagem , Masculino , Camundongos , MicroRNAs/agonistas , MicroRNAs/antagonistas & inibidores , Miocárdio/citologia , Miocárdio/metabolismo , Miócitos Cardíacos/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , Fosforilação/genética , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Regulação para Cima/efeitos dos fármacos
17.
Cancer Med ; 8(11): 5000-5011, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31293053

RESUMO

PURPOSE: This study aimed to investigate the characteristics of colonic neuroendocrine neoplasms (NENs) and to validate the prognostic value of the European Neuroendocrine Tumor Society (ENETS) and American Joint Committee on Cancer (AJCC) 8th staging systems. METHODS: A total of 167 and 1248 patients with colonic NENs from 12 medical centers across China and from the Surveillance, Epidemiology, and End Results (SEER) cancer registry in the United States, respectively, were reviewed. Patients were staged according to the ENETS and AJCC 8th staging systems. RESULTS: Clinicopathological features of colonic NENs in the Chinese cohort and SEER cohort were significantly distinct. In both the Chinese cohort and the SEER cohort, colonic neuroendocrine carcinoma (NEC) and mixed adeno-neuroendocrine carcinoma (MANEC) were more frequent in the midgut than in the hindgut. Tumors originating from the midgut tended to be larger and at a more advanced stage than those from the hindgut. The AJCC 8th staging system and the ENETS system appeared to have similar prognostic ability for colonic NEC/MANEC. CONCLUSIONS: Our study revealed that tumors originating from the midgut and the hindgut shared different clinicopathological features. The AJCC 8th staging system and the ENETS system appeared to have similar prognostic ability for colonic NEC/MANEC.


Assuntos
Neoplasias do Colo/diagnóstico , Estadiamento de Neoplasias/métodos , Estadiamento de Neoplasias/normas , Tumores Neuroendócrinos/diagnóstico , Adulto , Idoso , China , Neoplasias do Colo/epidemiologia , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Gradação de Tumores , Tumores Neuroendócrinos/epidemiologia , Guias de Prática Clínica como Assunto , Prognóstico , Sistema de Registros , Estudos Retrospectivos , Programa de SEER , Carga Tumoral
18.
Neoplasia ; 21(3): 311-321, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30772768

RESUMO

DNA methylation is an important epigenetic change in carcinogenesis. However, the function and mechanism of DNA methylation dysregulation in nasopharyngeal carcinoma (NPC) is still largely unclear. Our previous genome-wide microarray data showed that NFAT1 is one of the most hypermethylated transcription factor genes in NPC tissues. Here, we found that NFAT1 hypermethylation contributes to its down-regulation in NPC. NFAT1 overexpression inhibited cell migration, invasion, and epithelial-mesenchymal transition in vitro and tumor metastasis in vivo. We further established that the tumor suppressor effect of NFAT1 is mediated by its inactivation of ITGA6 transcription. Our findings suggest the significance of activating NFAT1/ITGA6 signaling in aggressive NPC, defining a novel critical signaling mechanism that drives NPC invasion and metastasis and providing a novel target for future personalized therapy.


Assuntos
Metilação de DNA , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica , Integrina alfa6/genética , Fatores de Transcrição NFATC/genética , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/patologia , Ativação Transcricional , Linhagem Celular Tumoral , Epigênese Genética , Perfilação da Expressão Gênica , Humanos , Metástase Linfática , Estadiamento de Neoplasias , Interferência de RNA , Transcriptoma
19.
J Exp Clin Cancer Res ; 38(1): 11, 2019 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-30621723

RESUMO

BACKGROUND: Increasing evidence support an important role for DNA methylation in nasopharyngeal carcinoma (NPC). Here, we explored the role of circadian clock gene Aryl Hydrocarbon Receptor Nuclear Translocator-Like (ARNTL) methylation in NPC. METHODS: We employed bisulfite pyrosequencing to determine the epigenetic change of ARNTL in NPC cell lines and tissues. ARNTL mRNA and protein expression in cell lines and tissues were detected by real-time PCR and western blotting. Then, we constructed cell lines overexpressing ARNTL and knocked down ARNTL to explore its function and effect on chemotherapy sensitivity of NPC cell lines to cisplatin in vitro and vivo. Finally, we investigated the potential molecular mechanism of ARNTL by gene set enrichment analysis (GSEA), dual Luciferase reporter assay and chromatin immunoprecipitation assay. RESULTS: ARNTL was hypermethylated, and its mRNA and protein were significantly down-regulated in NPC cell lines and tissues. When treated by 5-aza-2'-deoxycytidine, mRNA expression was up-regulated. Overexpression of ARNTL could suppress NPC cells proliferation in vitro and vivo while silencing of ARNTL using shRNA achieved opposite results. GSEA assay found that ARNTL was associated with cell cycle and ectopic ARNTL overexpression could induce G2-M phase arrest. Then, we identified and validated cyclin-dependent kinase 5 (CDK5) as the targeting gene of ARNTL by dual Luciferase reporter assay and chromatin immunoprecipitation assay. When transiently infected ARNTL-overexpression cells with PENTER-vector or PENTER-CDK5 plasmids, the later could reverse the suppressive effects of ARNTL on NPC cell proliferation. Moreover, ARNTL significantly enhanced sensitivity to cisplatin in NPC cells. CONCLUSIONS: ARNTL suppresses NPC cell proliferation and enhances sensitivity to cisplatin by targeting CDK5. ARNTL may represent a novel therapeutic target for NPC.


Assuntos
Fatores de Transcrição ARNTL/genética , Cisplatino/farmacologia , Quinase 5 Dependente de Ciclina/genética , Metilação de DNA , Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/genética , Fatores de Transcrição ARNTL/metabolismo , Animais , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Quinase 5 Dependente de Ciclina/biossíntese , Resistencia a Medicamentos Antineoplásicos , Feminino , Células HEK293 , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Carcinoma Nasofaríngeo/metabolismo , Carcinoma Nasofaríngeo/patologia , Distribuição Aleatória , Transcrição Genética
20.
Zhonghua Nan Ke Xue ; 25(9): 780-786, 2019 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-32233203

RESUMO

Objective: To identify differentially expressed proteins in the sperm of oligoasthenozoospermia (OAZ) patients and provide some theoretical evidence for the study of OAZ. METHODS: We collected semen samples from 30 OAZ patients and another 30 normal healthy males. Using the tandem mass tag (TMT) and proteomic technology, we identified differentially expressed proteins in the sperm of the OAZ patients and normal subjects, followed by gene ontology (GO) analysis and bioinformatics analysis of the Kyoto encyclopedia of genes and genomes (KEGG) signaling pathways. RESULTS: A total of 1 199 differentially expressed sperm proteins were obtained from the semen samples of the subjects by proteomic technology, of which 663 were up-regulated and 536 down-regulated. GO analysis preliminarily indicated that the differential proteins played a leading role in the composition and function of the ribosome, while KEGG pathway analysis showed that the differential proteins were involved in 244 signaling pathways. CONCLUSIONS: Differentially expressed proteins in the sperm of OAZ patients involve complex biological processes, molecular functions and signaling pathways, and proteomic screening and bioinformatics analysis are helpful for the study of the pathogenesis of oligoasthenozoospermia.


Assuntos
Biologia Computacional , Proteínas/metabolismo , Proteômica , Espermatozoides/metabolismo , Estudos de Casos e Controles , Humanos , Masculino , Transdução de Sinais
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