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1.
Angew Chem Int Ed Engl ; 63(23): e202405405, 2024 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-38578834

RESUMEN

The surface frustrated Lewis pairs (SFLPs) open up new opportunities for substituting noble metals in the activation and conversion of stable molecules. However, the applications of SFLPs on a larger scale are impeded by the complex construction process, low surface density, and sensitivity to the reaction environment. Herein, wurtzite-structured crystals such as GaN, ZnO, and AlP are found for developing natural, dense, and stable SFLPs. It is revealed that the SFLPs can naturally exist on the (100) and (110) surfaces of wurtzite-structured crystals. All the surface cations and anions serve as the Lewis acid and Lewis base in SFLPs, respectively, contributing to the surface density of SFLPs as high as 7.26×1014 cm-2. Ab initio molecular dynamics simulations indicate that the SFLPs can keep stable under high temperatures and the reaction atmospheres of CO and H2O. Moreover, outstanding performance for activating the given small molecules is achieved on these natural SFLPs, which originates from the optimal orbital overlap between SFLPs and small molecules. Overall, these findings not only provide a simple method to obtain dense and stable SFLPs but also unfold the nature of SFLPs toward the facile activation of small molecules.

2.
Water Sci Technol ; 87(7): 1713-1731, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37051793

RESUMEN

In this article, COD, volatile phenol and ammonia nitrogen concentrations of the wastewater from semicarbon are reported as 38,000; 6,400 and 5,700 mg/L, respectively. According to the field test, when the pH of the wastewater is 9, the field test temperature is 20 °C, the adsorption time is 30 min and the optimal dosing ratio of nitrogen-doped gasification slag (HX-NGS) to the wastewater is 1:4, HX-NGS has the best removal effect on COD, volatile phenol and ammonia nitrogen in the wastewater from the semicarbon. The removal rates of COD, volatile phenol and ammonia nitrogen are 94, 91 and 85%, respectively, and the concentrations of the remaining COD, volatile phenol and ammonia nitrogen are 2,280, 576 and 855 mg/L, respectively, after regeneration, the material HX-NGS has a good effect on the treatment of the wastewater from the semicarbon. The reuse rate of the adsorption material is at least eight times. The adsorption effect of the material HX-NGS conforms to the mechanism law of dynamics and thermodynamics.


Asunto(s)
Carbono , Aguas Residuales , Adsorción , Amoníaco , Fenol , Fenoles , Nitrógeno , Reactores Biológicos
3.
Zhonghua Nan Ke Xue ; 29(12): 986-991, 2023 Dec.
Artículo en Zh | MEDLINE | ID: mdl-38639950

RESUMEN

OBJECTIVE: To explore the effect of a novel transurethral thulium laser vapoenucleation of the prostate with low-power conventional pulse mode (LP-ThuVEP) on sexual function in patients with benign prostatic hyperplasia (BPH). METHODS: 89 BPH patients admitted to Department of Urology, Jintan People's Hospital, Affiliated to Jiangsu University, from January 2022 to June 2023 were selected and randomly divided into the LP-ThuLEP group (45 cases) and the transurethral plasma kinetic resection of the prostate (TUPKRP) group (44 cases). Perioperative indicators were recorded, and the IPSS, Qmax, Qavg, PVR, and QoL of the two groups of patients before surgery and 3 months and 6 months after surgery were comparatively analyzed. The effect of surgery on male sexual function was evaluated through the International Index of Erectile Function-5 (IIEF-5) score and the Male Sexual Health Questionnaire-Ejaculatory Dysfunction (MSHQ-EjD) score. RESULTS: Compared with the TUPKRP group, the LP-ThuVEP group had no statistically significant difference in operation time (P>0.05), but there were statistical differences in bladder irrigation time and indwelling urinary catheter time (P<0.05) and significant statistical differences in the decrease in hemoglobin on the day of surgery and the disappearance time of gross hematuria induced by defecation after surgery (P<0.001). The perioperative complications of the two groups were comparable. Among the urinary tract symptom indicators, the LP-ThuVEP group had statistically significant differences in IPSS score, QoL score, and PVR compared with the TUPKRP group 3 months after surgery (P<0.05). In terms of male sexual function, there was a statistical difference in IIEF-5 scores between the two groups at 3 months and 6 months after surgery (P<0.05); Except that there was no statistical difference in the ejaculation-related satisfaction scores between the two groups at 3 months after surgery (P>0.05), there had all significant statistical differences in ejaculation function and satisfaction scores between and within the groups at 3 months and 6 months after surgery (P<0.001). CONCLUSION: Compared with TUPKRP, the LP-ThuVEP can also effectively relieve urinary tract obstruction caused by BPH and has the advantages of less damage and faster recovery of erectile function and ejaculatory function of patients.


Asunto(s)
Disfunción Eréctil , Terapia por Láser , Hiperplasia Prostática , Resección Transuretral de la Próstata , Humanos , Masculino , Próstata/cirugía , Hiperplasia Prostática/cirugía , Disfunción Eréctil/cirugía , Calidad de Vida , Resultado del Tratamiento
4.
Apoptosis ; 27(1-2): 1-13, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-35064425

RESUMEN

Pyroptosis is a newly discovered form of programmed cell death mediated by the gasdermin protein, that is accompanied by inflammation and immune response. A growing body of evidence suggests that pyroptosis is closely related to cancer, and it is becoming a new cancer research topic. Studies have suggested that different cancer cells activate pyroptosis in different ways and that the effects of pyroptosis vary in different cancer backgrounds. In this article, we briefly introduce the definition, characteristics, and activation pathways of pyroptosis. Then we review the complex effects of pyroptosis on cancer development, which generally include inhibition of cancer cell viability, impacts on the invasion and migration of cancer cells, improvement of antitumor immunity, and enhancement of chemotherapy sensitivity. We also discuss drugs and compounds that can induce pyroptosis, as well as the interaction between pyroptosis and apoptosis. Elucidating the mechanisms of the complex effects of pyroptosis is likely to pave the way for therapeutic approaches for cancer in the future.


Asunto(s)
Neoplasias , Piroptosis , Apoptosis , Humanos , Inflamación/tratamiento farmacológico , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Neoplasias/metabolismo , Piroptosis/fisiología
5.
Zhonghua Nan Ke Xue ; 26(3): 242-249, 2020 Mar.
Artículo en Zh | MEDLINE | ID: mdl-33346964

RESUMEN

OBJECTIVE: To compare the clinical effect and safety of monoplane holmium laser enucleation of the prostate (MP-HoLEP) from those of biplane HoLEP (BP-HoLEP) in the treatment of large-volume BPH. METHODS: We retrospectively analyzed the clinical data on 67 cases of large-volume BPH treated in Jintan People's Hospital from June 2017 to December 2018, 30 by MP-HoLEP with incisions at 5- and 7-o'clock positions beside the verumontanum and the other 37 by BP-HoLEP with incision at 12 o'clock in the bladder neck to expose the surgical capsule layer. We compared the perioperative, postoperative and follow-up data between the two groups of patients. RESULTS: There were no statistically significant differences between the two groups of patients in the age, disease course, prostate volume or preoperative post-void residual urine volume (PVR), maximum urine flow rate (Qmax), IPSS, PSA level and quality of life score (QOL). Compared with the patients in the MP-HoLEP group, those treated by BP-HoLEP showed a significantly shorter operation time (ï¼»97.65 ± 34.72ï¼½ vs ï¼»125.46 ± 47.58ï¼½ min, P < 0.01) and tissue-enucleation time (ï¼»60.34 ± 23.45ï¼½ vs ï¼»97.43 ± 35.51ï¼½ min, P < 0.01) and lower intraoperative level of hemoglobin (ï¼»14.58 ± 1.11ï¼½ vs ï¼»21.44 ± 1.28ï¼½ g, P < 0.01). Statistically significant differences were not observed in the intraoperative adverse events, volume of the resected tissue, time of bladder irrigation or length of postoperative hospital stay, nor in the incidence of transient urinary incontinence (33% vs36.8%, P > 0.05). PVR, Qmax, IPSS and QOL were improved similarly in both of the groups at 6 months postoperatively. CONCLUSIONS: Both MP-HoLEP and BP-HoLEP are definitely effective for the treated of large-volume BPH, but the latter is superior to the former for shorter operation and enucleation time and less bleeding.


Asunto(s)
Terapia por Láser , Láseres de Estado Sólido , Hiperplasia Prostática , Holmio , Humanos , Masculino , Hiperplasia Prostática/cirugía , Calidad de Vida , Estudios Retrospectivos , Resultado del Tratamiento
6.
Nucleic Acids Res ; 42(18): 11560-9, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-25249620

RESUMEN

Human single-strand (ss) DNA binding proteins 1 (hSSB1) has been shown to participate in DNA damage response and maintenance of genome stability by regulating the initiation of ATM-dependent signaling. ATM phosphorylates hSSB1 and prevents hSSB1 from ubiquitin-proteasome-mediated degradation. However, the E3 ligase that targets hSSB1 for destruction is still unknown. Here, we report that hSSB1 is the bona fide substrate for an Fbxl5-containing SCF (Skp1-Cul1-F box) E3 ligase. Fbxl5 interacts with and targets hSSB1 for ubiquitination and degradation, which could be prevented by ATM-mediated hSSB1 T117 phosphorylation. Furthermore, cells overexpression of Fbxl5 abrogated the cellular response to DSBs, including activation of ATM and phosphorylation of ATM targets and exhibited increased radiosensitivity, chemosensitivity and defective checkpoint activation after genotoxic stress stimuli. Moreover, the protein levels of hSSB1 and Fbxl5 showed an inverse correlation in lung cancer cells lines and clinical lung cancer samples. Therefore, Fbxl5 may negatively modulate hSSB1 to regulate DNA damage response, implicating Fbxl5 as a novel, promising therapeutic target for lung cancers.


Asunto(s)
Daño del ADN , Proteínas de Unión al ADN/metabolismo , Proteínas F-Box/metabolismo , Proteínas Mitocondriales/metabolismo , Ubiquitina-Proteína Ligasas/metabolismo , Animales , Proteínas de la Ataxia Telangiectasia Mutada/metabolismo , Línea Celular Tumoral , Proteínas Cullin/metabolismo , Proteínas F-Box/fisiología , Humanos , Neoplasias Pulmonares/enzimología , Neoplasias Pulmonares/metabolismo , Masculino , Ratones Desnudos , Fosforilación , Proteolisis , Complejos de Ubiquitina-Proteína Ligasa , Ubiquitina-Proteína Ligasas/fisiología , Ubiquitinación
7.
J Cell Mol Med ; 19(3): 651-63, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25712415

RESUMEN

The large tumour suppressor 1 (LATS1) signalling network has been proved to be an essential regulator within the cell, participating in multiple cellular phenotypes. However, it is unclear concerning the clinical significance of LATS1 and the regulatory mechanisms of 17-Allylamino-17- demethoxygeldanamycin (17-AAG) in lung adenocarcinoma (LAC). The aim of the present study was to investigate the correlation of LATS1 and yes-associated protein (YAP) expression with clinicopathological characteristics in LAC patients, and the effects of 17-AAG on biological behaviours of LAC cells. Subcutaneous LAC tumour models were further established to observe the tumour growth in nude mice. The results showed that the positive expression of LATS1 was significantly lowered (26.7% versus 68.0%, P < 0.001), while that of YAP was elevated (76.0% versus 56.0%, P = 0.03) in LAC tissues compared to the adjacent non-cancerous tissues; LAST1 expression was negatively correlated with YAP expression (r = 0.432, P < 0.001) and lymphatic invasion of the tumour (P = 0.015). In addition, 17-AAG inhibited proliferation and invasion, and induced cell apoptosis and cycle arrest in LAC cells together with increased expression of E-cadherin and p-LATS1, and decreased expression of YAP and connective tissue growth factor. Tumour volumes and weight were much smaller in 17-AAG-treated groups than those in untreated group (P < 0.01). Taken together, our findings indicate that decreased expression of LATS1 is associated with lymphatic invasion of LAC, and 17-AAG suppresses growth and invasion of LAC cells via regulation of the LATS1/YAP pathway in vitro and in vivo, suggesting that we may provide a promising therapeutic strategy for the treatment of human LAC.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/metabolismo , Adenocarcinoma/tratamiento farmacológico , Apoptosis/efectos de los fármacos , Benzoquinonas/farmacología , Lactamas Macrocíclicas/farmacología , Neoplasias Pulmonares/tratamiento farmacológico , Fosfoproteínas/metabolismo , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Adaptadoras Transductoras de Señales/biosíntesis , Adenocarcinoma del Pulmón , Animales , Antineoplásicos/farmacología , Cadherinas/biosíntesis , Puntos de Control del Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Factor de Crecimiento del Tejido Conjuntivo/biosíntesis , Femenino , Regulación Neoplásica de la Expresión Génica , Proteínas HSP90 de Choque Térmico/antagonistas & inhibidores , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Persona de Mediana Edad , Invasividad Neoplásica/patología , Fosfoproteínas/biosíntesis , Proteínas Serina-Treonina Quinasas/biosíntesis , Transducción de Señal/efectos de los fármacos , Factores de Transcripción , Ensayos Antitumor por Modelo de Xenoinjerto , Proteínas Señalizadoras YAP
8.
Biomolecules ; 14(7)2024 Jul 22.
Artículo en Inglés | MEDLINE | ID: mdl-39062593

RESUMEN

This study sought to explore potential roles of endothelial ferroptosis in radiation-associated atherosclerosis (RAA) and molecular mechanisms behind this phenomenon. Here, an in vivo RAA mouse model was used and treated with ferroptosis inhibitors. We found that the RAA group had a higher plaque burden and a reduction in endothelial cells with increased lipid peroxidation compared to the control group, while ameliorated by liproxstatin-1. In vitro experiments further confirmed that radiation induced the occurrence of ferroptosis in human artery endothelial cells (HAECs). Then, proteomics analysis of HAECs identified domain-containing protein 2 (DDHD2) as a co-differentially expressed protein, which was enriched in the lipid metabolism pathway. In addition, the level of lipid peroxidation was elevated in DDHD2-knockdown HAECs. Mechanistically, a significant decrease in the protein and mRNA expression of glutathione peroxidase 4 (GPX4) was observed in HAECs following DDHD2 knockdown. Co-immunoprecipitation assays indicated a potential interaction between DDHD2 and nuclear factor erythroid 2-related factor 2 (Nrf2). The downregulation of Nrf2 protein was also detected in DDHD2-knockdown HAECs. In conclusion, our findings suggest that radiation-induced endothelial ferroptosis accelerates atherosclerosis, and DDHD2 is a potential regulatory protein in radiation-induced endothelial ferroptosis through the Nrf2/GPX4 pathway.


Asunto(s)
Aterosclerosis , Células Endoteliales , Ferroptosis , Factor 2 Relacionado con NF-E2 , Fosfolipasas , Fosfolípido Hidroperóxido Glutatión Peroxidasa , Animales , Humanos , Masculino , Ratones , Aterosclerosis/metabolismo , Aterosclerosis/patología , Aterosclerosis/etiología , Aterosclerosis/genética , Células Endoteliales/metabolismo , Células Endoteliales/patología , Peroxidación de Lípido , Ratones Endogámicos C57BL , Factor 2 Relacionado con NF-E2/metabolismo , Factor 2 Relacionado con NF-E2/genética , Fosfolípido Hidroperóxido Glutatión Peroxidasa/metabolismo , Fosfolípido Hidroperóxido Glutatión Peroxidasa/genética , Transducción de Señal , Fosfolipasas/genética , Fosfolipasas/metabolismo
9.
Tumour Biol ; 34(5): 2611-5, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-23653378

RESUMEN

There were many studies performed to assess the association between X-ray repair cross-complementing group 1 (XRCC1) Arg194Trp polymorphism and lung cancer risk in Chinese Han population, but contradictory results were reported. To provide a comprehensive and objective assessment of the association, a meta-analysis of all eligible case-control studies was carried out. After searching the databases and reading the abstracts, 12 case-control studies on the association between XRCC1 Arg194Trp polymorphism and lung cancer risk were finally included into this meta-analysis. Those 12 studies included a total of 4,385 cases and 4,545 controls. XRCC1 Arg194Trp polymorphism was associated with increased risk of lung cancer in Chinese Han population under three main models (allele contrast model, odds ratio (OR) = 1.12, 95 % confidence interval (CI) 1.00-1.26, P = 0.049; homozygote model, OR = 1.27, 95 % CI 1.09-1.48, P = 0.003; recessive model, OR = 1.26, 95 % CI 1.09-1.46, P = 0.003). However, there was no obvious association between XRCC1 Arg194Trp polymorphism and lung cancer risk under the dominant model (OR = 1.06, 95 % CI 0.98-1.16, P = 0.146). Sensitivity analysis suggested the stability and liability of this meta-analysis. Therefore, this meta-analysis suggests that XRCC1 Arg194Trp polymorphism is associated with increased risk of lung cancer in Chinese Han population.


Asunto(s)
Proteínas de Unión al ADN/genética , Neoplasias Pulmonares/genética , Polimorfismo de Nucleótido Simple , Sustitución de Aminoácidos , Estudios de Casos y Controles , China , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Humanos , Factores de Riesgo , Proteína 1 de Reparación por Escisión del Grupo de Complementación Cruzada de las Lesiones por Rayos X
10.
Tumour Biol ; 34(2): 865-74, 2013 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-23300009

RESUMEN

The development of lung cancer is significantly associated with genetic susceptibility. Findings from previous individual studies regarding the effect of X-ray repair cross-complementing group 3 Thr241Met (XRCC3 Thr241Met) polymorphism on lung cancer risk remained conflicting and inconclusive. Thus, a meta-analysis of previous relevant studies was performed to estimate this effect more precisely and to shed some light on the contradictory findings. The pooled odds ratios (ORs) with the corresponding 95 % confidence intervals (95 % CIs) were calculated to assess the correlation of XRCC3 Thr241Met polymorphism with lung cancer susceptibility. Stratified analysis according to ethnicity and sensitivity analysis was both conducted for further confirmation. Seventeen independent case-control studies involving 12,610 subjects totally were included into this meta-analysis. Overall, meta-analysis of total included studies showed that the XRCC3 Thr241Met polymorphism was not associated with risk of lung cancer in all genetic contrast models (OR Met allele vs. Thr allele = 1.01, 95 % CI 0.91-1.13, P OR = 0.810; OR Met/Met vs. Thr/Thr = 1.16, 95 % CI 0.88-1.54, P OR = 0.281; OR Thr/Met vs. Thr/Thr = 0.95, 95 % CI 0.86-1.04, P OR = 0.240; OR Met/Met + Thr/Met vs. Thr/Thr = 0.97, 95 % CI 0.89-1.06, P OR = 0.538; OR Met/Met vs. Thr/Thr + Thr/Met = 1.18, 95 % CI 0.91-1.52, P OR = 0.204). Stratified analyses in Asians and Caucasians showed similar results. Sensitivity analysis confirmed the stability and reliability of the findings. This meta-analysis of all available data did not support any appreciable association between the XRCC3 Thr241Met polymorphism and lung cancer risk in any populations.


Asunto(s)
Proteínas de Unión al ADN/genética , Neoplasias Pulmonares/etiología , Polimorfismo Genético/genética , Estudios de Casos y Controles , Predisposición Genética a la Enfermedad , Humanos , Factores de Riesgo
11.
Acta Crystallogr Sect E Struct Rep Online ; 68(Pt 4): o1134, 2012 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-22606083

RESUMEN

The title compound, C(13)H(11)BrN(2)O(2), consists of two six-membered rings linked by an amide group and adopts a near planar conformation. The dihedral angle between the two rings is 8.38 (11)°. In the crystal structure, there are intra- and inter-molecular N-H⋯O hydrogen bonds, the latter forming inversion dimers.

12.
Front Comput Neurosci ; 16: 1052140, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36518995

RESUMEN

At present, gold and bitcoin have become mainstream assets in market transactions. Due to the volatility of gold and bitcoin prices, we can buy and sell assets like gold and bitcoin the same way we buy and sell stocks. The research goal of this article is to develop an optimal trading strategy that maximizes our post-trade returns. By studying the relationship between the two, on the one hand, it supplements and enriches the theoretical research on the rate of return of gold and Bitcoin, on the other hand, it provides a certain reference for investors to construct investment strategies. The research on the cointegration relationship between them has important practical significance. At the same time, it has important practical significance for the research on the cointegration relationship between bitcoin and gold.

13.
Zhonghua Zhong Liu Za Zhi ; 33(5): 395-9, 2011 May.
Artículo en Zh | MEDLINE | ID: mdl-21875475

RESUMEN

OBJECTIVE: To evaluate the efficacy of short-term intermittent prophylactic use of a recombinant human thrombopoietin (rhTPO) in chemotherapy-induced severe thrombocytopenia in lung cancer patients. METHODS: 24 advanced non-small cell lung cancer (NSCLC) patients who experienced severe thrombocytopenia in the last chemotherapy cycle received prophylactic rhTPO treatment in the next chemotherapy cycle (prophylactic treated cycle, PTC). rhTPO was given subcutaneously 300 U×kg(-1)×d(-1) on days 2, 4, 6, and 9 after the initiation of chemotherapy. Platelet count was monitored and compared with that in the previous treatment cycle (control cycle, CC). RESULTS: The lowest platelet count in the prophylactic rhTPO cycle was significantly higher than that in control cycle [(56 ± 16) × 10(9)/L vs. (28 ± 13) × 10(9)/L, P < 0.001]. The duration of thrombocytopenia was also shortened by the prophylactic rhTPO [(8 ± 2) d vs. (12 ± 3) d, P < 0.001]. The area under curve (AUC) of platelet count (21 days) was significantly increased [(3517 ± 685) × 10(9)/L vs. (2063 ± 436) × 10(9)/L, P < 0.001]. The time to platelet nadir and peak was not affected. CONCLUSION: Prophylactic use of rhTPO can attenuate the severity and shorten the duration of chemotherapy-induced thrombocytopenia in lung cancer patients.


Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias Pulmonares/tratamiento farmacológico , Trombocitopenia/tratamiento farmacológico , Trombopoyetina/uso terapéutico , Adenocarcinoma/sangre , Adenocarcinoma/patología , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Área Bajo la Curva , Carboplatino/administración & dosificación , Carboplatino/efectos adversos , Cisplatino/administración & dosificación , Cisplatino/efectos adversos , Desoxicitidina/administración & dosificación , Desoxicitidina/efectos adversos , Desoxicitidina/análogos & derivados , Mareo/inducido químicamente , Femenino , Fiebre/inducido químicamente , Humanos , Neoplasias Pulmonares/sangre , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Recuento de Plaquetas , Proteínas Recombinantes/efectos adversos , Proteínas Recombinantes/uso terapéutico , Trombocitopenia/sangre , Trombocitopenia/inducido químicamente , Trombopoyetina/efectos adversos , Gemcitabina
14.
Front Oncol ; 10: 916, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32695665

RESUMEN

Coronin 2A (CORO2A) is a novel component of the N-CoR (nuclear receptor co-repressor) complex. Abnormal CORO2A expression is associated with carcinogenesis. We used databases from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), and analyzed CORO2A expression and gene regulation networks in breast cancer. Expression was analyzed using GEO and TCGA database and further validated in breast cancer samples collected in our clinic. The prognostic value of CORO2A was explored by using the Kaplan-Meier survival analysis and Cox proportional hazards regression analysis. LinkedOmics was used to identify coexpressed genes associated with CORO2A. After analyzing the intersection of coexpressed genes correlated with CORO2A and differentially expressed genes after CORO2A silencing, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses of the intersecting genes were conducted by using FunRich software. Transwell assays were performed in breast cancer cells to determine the effect of CORO2A on cell migration. MTS, colony formation, and cell cycle distribution assays were performed in breast cancer cells to determine the effect of CORO2A on cell proliferation. Gene enrichment analysis was employed to explore the target networks of transcription factors and miRNAs. We found that CORO2A was upregulated and that the elevated expression of CORO2A was associated with poor overall survival (OS) and relapse-free survival (RFS) in TNBC patients. Further bioinformatics analysis of public sequencing data and our own RNA-Seq data revealed that CORO2A was probably involved in the epithelial-to-mesenchymal transition process and might have a significant effect on the migration of breast cancer cells, which might be mediated via pathways involving several miRNAs and MYC transcription factors. Functionally, the knockdown of CORO2A inhibited cell migration, decreased viability, and colony formation and induced cell cycle arrest in the G0/G1 phase in breast cancer cells. These results demonstrate that bioinformatics-based analysis efficiently reveals information about CORO2A expression and its potential regulatory networks in breast cancer, laying a foundation for further mechanistic research on the role of CORO2A in carcinogenesis. Moreover, CORO2A promotes the migration and proliferation of breast cancer cells and may have an important function in breast cancer progression. CORO2A is a potential prognostic predictor for TNBC patients. Targeting CORO2A may provide promising therapy strategies for breast cancer treatment.

15.
Gastroenterol Rep (Oxf) ; 8(5): 390-398, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-33163195

RESUMEN

BACKGROUND: The epithelial-to-mesenchymal transition (EMT) status is associated with programmed death-1 ligand 1 (PD-L1) expression in various cancers. However, the role and molecular mechanism of PD-L1 in the EMT of sorafenib-resistant hepatocellular carcinoma (HCC) cells remain elusive. In this study, we aimed to investigate the regulation of PD-L1 on the EMT in sorafenib-resistant HCC cells. METHODS: Initially, the sorafenib-resistant HCC cell lines HepG2 SR and Huh7 SR were established. Western-blot assays were used to detect the expression of PD-L1, E-cadherin, and N-cadherin. The intervention and overexpression of PD-L1 were used to explore the role of PD-L1 in the regulation of EMT in HepG2 SR and Huh7 SR cells. Cell migration and invasion were assessed by transwell assays. PD-L1 or Sterol regulatory element-binding protein 1 (SREBP-1) overexpression and knock-down were performed in order to study the mechanism of PD-L1 in sorafenib-resistant HCC cells. RESULTS: PD-L1 expression was upregulated, whereas E-cadherin levels were downregulated and N-cadherin expression was increased in HepG2 SR and Huh7 SR cells. The cell viabilities of HepG2 and Huh7 cells were lower than those of HepG2 SR and Huh7 SR cells. PD-L1 overexpression reduced E-cadherin expression and increased N-cadherin levels, whereas PD-L1 knock-down increased E-cadherin expression and decreased N-cadherin expression. PD-L1 expression promoted EMT and the migratory and invasive abilities of HepG2 SR and Huh7 SR cells. PD-L1 promoted the EMT of sorafenib-resistant HCC cells via the PI3K/Akt pathway by activating SREBP-1 expression in HepG2 SR and Huh7 SR cells. CONCLUSIONS: The findings reveal that PD-L1 expression promotes EMT of sorafenib-resistant HCC cells.

16.
DNA Cell Biol ; 39(7): 1205-1227, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-32456464

RESUMEN

Breast cancer (BC) is the most malignant tumor in women. The molecular mechanisms underlying tumorigenesis still need to be further elucidated. It is necessary to investigate novel candidate genes involved in breast cancer progression and prognosis. In this study, we commit to explore candidate genes that associate with prognosis and therapy in BC by a comprehensive bioinformatic analysis. Four GEO datasets (GSE5764, GSE7904, GSE20711, and GSE29431) and the BC-related transcriptome data in TCGA database were downloaded and used to identify the differently expressed genes (DEGs). The function of DEGs was analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enrichment analysis. The protein-protein interaction (PPI) network of DEGs was constructed to identify hub genes. Prognostic candidate genes were identified through survival analysis. In addition, potential therapeutic targets were identified by constructed gene-drug interaction network through Comparative Toxicogenomics Database. A total of 547 DEGs (302 up and 245 down) were identified. Three core-subnetwork and 25 hub genes were identified in PPI network. Seven genes (namely COL12A1, QPRT, MRPL13, KRT14, KRT15, LAMB3, and MYBPC1) were identified as crucial prognostic candidate genes, which significantly associated with breast cancer overall survival. Furthermore, two representative candidate genes (COL12A1 and LAMB3) were optionally chosen for verification by reverse transcription and quantitative real-time polymerase chain reaction (RT-PCR). What's more, the gene-drugs interaction analysis indicates several antitumor drugs that could affect the expression of these prognostic markers, such as doxorubicin, cisplatin, and tamoxifen. These results identified seven crucial candidate genes that may serve as prognosis biomarkers and novel therapeutic targets of breast cancer, which may facilitate further understanding the molecular pathogenesis and providing potential therapeutic strategies for BC.


Asunto(s)
Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/genética , Biología Computacional , Neoplasias de la Mama/tratamiento farmacológico , Perfilación de la Expresión Génica , Humanos , Terapia Molecular Dirigida , Pronóstico , Mapeo de Interacción de Proteínas
17.
Front Genet ; 10: 695, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31428132

RESUMEN

Background: The molecular mechanism of tumorigenesis remains to be fully understood in breast cancer. It is urgently required to identify genes that are associated with breast cancer development and prognosis and to elucidate the underlying molecular mechanisms. In the present study, we aimed to identify potential pathogenic and prognostic differentially expressed genes (DEGs) in breast adenocarcinoma through bioinformatic analysis of public datasets. Methods: Four datasets (GSE21422, GSE29431, GSE42568, and GSE61304) from Gene Expression Omnibus (GEO) and the Cancer Genome Atlas (TCGA) dataset were used for the bioinformatic analysis. DEGs were identified using LIMMA Package of R. The GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) analyses were conducted through FunRich. The protein-protein interaction (PPI) network of the DEGs was established through STRING (Search Tool for the Retrieval of Interacting Genes database) website, visualized by Cytoscape and further analyzed by Molecular Complex Detection (MCODE). UALCAN and Kaplan-Meier (KM) plotter were employed to analyze the expression levels and prognostic values of hub genes. The expression levels of the hub genes were also validated in clinical samples from breast cancer patients. In addition, the gene-drug interaction network was constructed using Comparative Toxicogenomics Database (CTD). Results: In total, 203 up-regulated and 118 down-regulated DEGs were identified. Mitotic cell cycle and epithelial-to-mesenchymal transition pathway were the major enriched pathways for the up-regulated and down-regulated genes, respectively. The PPI network was constructed with 314 nodes and 1,810 interactions, and two significant modules are selected. The most significant enriched pathway in module 1 was the mitotic cell cycle. Moreover, six hub genes were selected and validated in clinical sample for further analysis owing to the high degree of connectivity, including CDK1, CCNA2, TOP2A, CCNB1, KIF11, and MELK, and they were all correlated to worse overall survival (OS) in breast cancer. Conclusion: These results revealed that mitotic cell cycle and epithelial-to-mesenchymal transition pathway could be potential pathways accounting for the progression in breast cancer, and CDK1, CCNA2, TOP2A, CCNB1, KIF11, and MELK may be potential crucial genes. Further, it could be utilized as new biomarkers for prognosis and potential new targets for drug synthesis of breast cancer.

18.
Cancer Lett ; 464: 37-55, 2019 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-31465841

RESUMEN

Long noncoding RNAs (lncRNAs) are defined as RNA transcripts longer than 200 nucleotides that do not encode proteins. LncRNAs have been documented to exhibit aberrant expression in various types of cancer, including prostate cancer. Currently, screening for prostate cancer results in overdiagnosis. The consequent overtreatment of patients with indolent disease in the clinic is due to the lack of appropriately sensitive and specific biomarkers. Thus, the identification of lncRNAs as novel biomarkers and therapeutic targets for prostate cancer is promising. In the present review, we attempt to summarize the current knowledge of lncRNA expression patterns and mechanisms in prostate cancer. In particular, we focus on lncRNAs regulated by the androgen receptor and the specific molecular mechanism of lncRNAs in prostate cancer to provide a potential clinical therapeutic strategy for prostate cancer.


Asunto(s)
Neoplasias de la Próstata/genética , ARN Largo no Codificante/genética , Receptores Androgénicos/genética , Biomarcadores de Tumor/genética , Detección Precoz del Cáncer , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Terapia Molecular Dirigida , Pronóstico , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/tratamiento farmacológico
19.
J Cancer ; 10(18): 4341-4349, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31413754

RESUMEN

Purpose: The clinical utility of cell-free DNA (cfDNA) to assess EGFR mutations is increasing. However, there are limited studies determining their clinical validity and utility. The value of cfDNA assays in cancer management remains controversial. Methods: In this study, we first evaluated the analytical performance of the ddPCR Lung cfDNA Assay. We next analyzed the concordance of the results with tissue amplification refractory mutation system PCR (ARMS-PCR) and plasma next-generation sequencing (NGS) genotyping. Finally, we assessed its clinical utility by exploring the association of cfDNA EGFR mutations with metastatic sites and the efficacy of EGFR-TKIs treatment. Results: The ddPCR Lung cfDNA Assay demonstrated a limit of blank of 1 droplet per reaction, an analytical specificity of 100%, and detection limit of 0.05%, 0.05%, and 0.1% for E746_A750del, L858R, and T790M, respectively. With tissue ARMS-PCR as a standard for comparison, the clinical sensitivity and specificity of ddPCR were 62.5% (15/24) and 100% (82/82) for E746_A750del, and 75.0% (15/20) and 94.2% (81/86) for L858R, respectively. The ddPCR showed high concordance with NGS in determining cfDNA EGFR mutations. Patients with bone and/or brain metastasis showed a higher detection rate and mutant abundance of cfDNA EGFR mutations compared to those with other sites of metastasis. Moreover, EGFR-TKIs treatment was effective in patients with sensitive EGFR mutations in either plasma cfDNA or tumor tissue-derived DNA. Conclusions: We validated in this study that the ddPCR Lung cfDNA Assay is reliable for detection of EGFR mutations in lung cancers, in terms of analytical performance, clinical validity and utility.

20.
J Phys Chem B ; 112(6): 1611-8, 2008 Feb 14.
Artículo en Inglés | MEDLINE | ID: mdl-18201075

RESUMEN

Spin-coating one polymer solution on another spin-cast polymer film is believed to result in unfavorable interfacial mixing. Here, we show some results to demonstrate that some interesting properties will be obtained in such mixed bilayer films formed by sequential spin-coating. Poly(9-vinylcarbazole) and poly(9,9-dioctylfluorene-2,7-diyl) were chosen as the first and second polymer layers, respectively. By varying the initial thickness of the first layer, some interesting variations were observed. The spectroscopic features of beta-phase polyfluorene were utilized to reflect the variations at the complicated interface. Morphologies were also presented to illustrate that the variations of spectroscopic features were accompanied with some interesting morphological changes. On the basis of these results, a schematic model was proposed to gain insight into the mixed interface formed by sequential spin-coating. Polymer light-emitting devices based on such films were also investigated.

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