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1.
Clin Genitourin Cancer ; 22(3): 102085, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38636170

RESUMO

PURPOSE: To evaluate the efficacy and safety of a novel humanized anti-HER2 antibody, RC48-ADC (Disitamab vedotin, DV), the combination of RC48-ADC with PD-1 inhibitors was used to treat muscle-invasive bladder cancer (MIBC). This combination therapy has potential applications in both bladder preservation and neoadjuvant therapy for MIBC. METHODS: Patients with MIBC underwent transurethral resection of bladder tumors followed by RC48-ADC alone or in combination with PD-1 inhibitors. Radiological and endoscopic evaluations were conducted 3 months later. The primary endpoint was objective response rate (ORR), with secondary endpoints including complete response rate (CR), partial response rate (PR), and bladder preservation rate. Treatment safety was assessed according to RECIST v1.1 criteria. RESULTS: Eleven patients were enrolled, with a median follow-up of 19.0 months. Nine patients achieved objective response, including 6 CR and 3 PR cases. The pathological ORR was 81.8%. Eight patients continued combined treatment after 3 months, maintaining a 72.7% bladder preservation rate at 16 months. One elderly patient progressed from ypT2N0M0 to ypT3N0M0 and underwent radical cystectomy but had no recurrence or metastasis 12 months postoperation. All patients reported varying degrees of treatment-related adverse reactions, which were largely manageable. CONCLUSION: The combination of RC48-ADC and PD-1 inhibitors proves to be a viable and safe option for bladder-sparing therapy, particularly for T2-stage MIBC patients who are ineligible for surgery and chemotherapy. This approach offers a promising new direction for bladder preservation or neoadjuvant therapy in MIBC patients.


Assuntos
Inibidores de Checkpoint Imunológico , Neoplasias da Bexiga Urinária , Humanos , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/cirurgia , Masculino , Idoso , Feminino , Pessoa de Meia-Idade , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Resultado do Tratamento , Terapia Neoadjuvante/métodos , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , Cistectomia , Tratamentos com Preservação do Órgão/métodos , Invasividade Neoplásica , Idoso de 80 Anos ou mais
2.
Materials (Basel) ; 17(8)2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38673213

RESUMO

The dynamic mechanical behavior and cushioning performance of honeycomb sandwich panels, which are extensively employed in product cushioning packaging due to their exceptional energy absorption capabilities, were examined using a combination of experimental and numerical methods. Several factors, such as maximum acceleration-static stress, cushioning coefficient-static stress, and other curves, were analyzed under various impact conditions. The simulated stress-strain, deformation modes, cushioning coefficients, and other parameters demonstrate consistency with the experimental results. The acceleration, maximum compression, and cushioning coefficient obtained from the experiment and simulation calculation were 30.68 g, 15.44 mm, and 2.65, and 31.96 g, 14.91 mm, and 2.79, respectively. The results indicate that all error values were less than 5%, confirming the precision and reliability of the model. Furthermore, the model was utilized to simulate and predict the cushioning performance of honeycomb sandwich panels with different cell structures and paper thicknesses. These results provide a solid basis for enhancing the design of subsequent honeycomb element structures.

3.
Front Oncol ; 13: 1170567, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37260987

RESUMO

Purpose: Clear cell renal cell carcinoma (ccRCC) is the most common pathology type in kidney cancer. However, the prognosis of advanced ccRCC is unsatisfactory. Thus, early diagnosis becomes one of the most important research priorities of ccRCC. However, currently available studies about ccRCC lack urine-related further studies. In this study, we applied proteomics to search urinary biomarkers to assist early diagnosis of ccRCC. In addition, we constructed a prognostic model to assist judge patients' prognosis. Materials and methods: Urine which was used to perform 4D label-free quantitative proteomics was collected from 12 ccRCC patients and 11 non-tumor patients with no urinary system diseases. The urine of 12 patients with ccRCC confirmed by pathological examination after surgery was collected before operatoin. Bioinformatics analysis was used to describe the urinary proteomics landscape of these patients with ccRCC. The top ten proteins with the highest expression content were selected as the basis for subsequent validation. Urine from 46 ccRCC patients and 45 control patients were collected to use for verification by enzyme linked immunosorbent assay (ELISA). In order to assess the prognostic value of urine proteomics, a prognostic model was constructed by COX regression analysis on the intersection of RNA-sequencing data in The Cancer Genome Atlas (TCGA) database and our urine proteomic data. Results: 133 proteins differentially expressed in the urinary samples were found and 85 proteins (Fold Change, FC>1.5) were identified up-regulated while 48 down-regulated (FC<0.5). Top 10 proteins including S100A14, PKHD1L1, FABP4, ITIH2, C3, C8G, C2, ATF6, ANGPTL6, F13B were performed ELISA to verify. The results showed that PKHD1L1, ANGPTL6, FABP4 and C3 were statistically significant (P<0.05). We performed multivariate logistic regression analysis and plotted a nomogram. Receiver operating characteristic (ROC) curve indicted that the diagnostic efficiency of combined indicators is satisfactory (Aare under curve, AUC=0.835). Furthermore, the prognostic value of the urine proteomics was explored through the intersection between urine proteomics and TCGA RNA-seq data. Thus, COX regression analysis showed that VSIG4, HLA-DRA, SERPINF1, and IGLV2-23 were statistically significant (P<0.05). Conclusion: Our study indicated that the application of urine proteomics to explore diagnostic biomarkers and to construct prognostic models of renal clear cell carcinoma is of certain clinical value. PKHD1L1, ANGPTL6, FABP4 and C3 can assist to diagnose ccRCC. The prognostic model constituted of VSIG4, HLA-DRA, SERPINF1, and IGLV2-23 can significantly predict the prognosis of ccRCC patients, but this still needs more clinical trials to verify.

4.
Materials (Basel) ; 16(9)2023 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-37176288

RESUMO

Active packaging that can extend the shelf-life of fresh fruits and vegetables after picking can assure food quality and avoid food waste. Such packaging can prevent the growth of microbial and bacterial pathogens or delay the production of ethylene, which accelerates the ripening of fruits and vegetables after harvesting. Proposed technologies include packaging that enables the degradation of ethylene, modified atmosphere packaging, and bioactive packaging. Packaging that can efficiently adsorb/desorb ethylene, and thus control its concentration, is particularly promising. However, there are still large challenges around toxicity, low selectivity, and consumer acceptability. Metal-organic framework (MOF) materials are porous, have a specific surface area, and have excellent gas adsorption/desorption performance. They can encapsulate and release ethylene and are thus good candidates for use in ethylene-adjusting packaging. This review focuses on MOF-based active-packaging materials and their applications in post-harvest fruit and vegetable packaging. The fabrication and characterization of MOF-based materials and the ethylene adsorption/desorption mechanism of MOF-based packaging and its role in fruit and vegetable preservation are described. The design of MOF-based packaging and its applications are reviewed. Finally, the potential future uses of MOF-based active materials in fresh food packaging are considered.

5.
ChemistryOpen ; 11(11): e202200161, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36351758

RESUMO

Three-dimensional porous graphene (3D-PG) has attracted much attention due to its excellent electrochemical performance. Chemical reduction is one of common methods for preparing porous graphene. In order to develop a green and facile method for preparing three-dimensional porous graphene, in this paper, 3D-PG was fabricated by reduction of graphene oxide (GO) with ascorbic acid (AA) as reductant in hydrothermal condition based on non-toxic, non-flammable and mild reducing performance of ascorbic acid. It was found that the size and distribution of pores could be controlled by the reduction time and the concentration of AA in the solution. The pore sizes in R0, R1 and R2 were in the range of 0.5-1 µm, 1-1.5 µm, and 1.5-3 µm, respectively. It was found that the average pore size and volume increased along with the amount of reductants. Under optimal conditions - a reaction time of 20 h and a ratio of GO to AA=1 : 1 - the CV area of the so-obtained sample R1-20 at 100 mV was 0.06 and the specific capacitance of the 3D-PG electrode reaches 153.5 F ⋅ g-1 , which is suitable for use in supercapacitors.


Assuntos
Grafite , Grafite/química , Ácido Ascórbico/química , Técnicas Eletroquímicas/métodos , Porosidade
6.
Front Surg ; 9: 941104, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36386533

RESUMO

Objective: The limitations of tissue retraction and the amount of surgical working space have a great impact on extraperitoneal single-port robotic-assisted radical prostatectomy (sp-RARP) with the multiport robotic surgical system. We used an extraperitoneal tissue retraction technique to achieve tissue exposure and working space expansion. This study evaluated the safety, feasibility, and efficacy of the extraperitoneal tissue retraction technique in extraperitoneal pure sp-RARP with the da Vinci Si surgical system. Methods: Data from 42 patients were analyzed retrospectively from December 2018 to February 2020. The extraperitoneal tissue retraction technique was not used in 20 patients (group I) and was used in 22 patients (group II). Preoperative, intraoperative, and postoperative data were collected. The oncological and functional data during late follow-up were recorded. Results: All patients successfully underwent extraperitoneal pure sp-RARP. No patients required conversion to a multiport surgery or placement of additional assistant ports. The two groups were similar regarding baseline features. The median operation time in group I was significantly longer than that in group II (P < 0.001). The estimated blood loss volume in group I was significantly higher than that in group II (P < 0.001). There were no serious complications in either group. There were four cases of peritoneal tears in group I and none in group II (P = 0.043). The surgical margin and lymph nodes were negative in both groups. The oncological and functional outcomes were similar between the two groups 6 months after the procedure. Conclusions: The extraperitoneal tissue retraction technique is safe and feasible. The technique promotes tissue exposure and expands the surgical working space, which is important for achieving extraperitoneal pure sp-RARP with the da Vinci Si surgical system, especially for beginners. The short-term oncological and functional outcomes were within acceptable ranges. The long-term effects of this technique need further evaluation.

7.
Front Immunol ; 13: 874792, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35592316

RESUMO

The epigenetic modification of tumorigenesis and progression in neoplasm has been demonstrated in recent studies. Nevertheless, the underlying association of N7-methylguanosine (m7G) regulation with molecular heterogeneity and tumor microenvironment (TME) in clear cell renal cell carcinoma (ccRCC) remains unknown. We explored the expression profiles and genetic variation features of m7G regulators and identified their correlations with patient outcomes in pan-cancer. Three distinct m7G modification patterns, including MGCS1, MGCS2, and MGCS3, were further determined and systematically characterized via multi-omics data in ccRCC. Compared with the other two subtypes, patients in MGCS3 exhibited a lower clinical stage/grade and better prognosis. MGCS1 showed the lowest enrichment of metabolic activities. MGCS2 was characterized by the suppression of immunity. We then established and validated a scoring tool named m7Sig, which could predict the prognosis of ccRCC patients. This study revealed that m7G modification played a vital role in the formation of the tumor microenvironment in ccRCC. Evaluating the m7G modification landscape helps us to raise awareness and strengthen the understanding of ccRCC's characterization and, furthermore, to guide future clinical decision making.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Biomarcadores Tumorais/genética , Carcinoma de Células Renais/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Renais/genética , Microambiente Tumoral/genética
8.
Asian J Androl ; 23(6): 640-647, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34135173

RESUMO

To evaluate outcomes between extraperitoneal robotic single-port radical prostatectomy (epR-spRP) and extraperitoneal robotic multiport radical prostatectomy (epR-mpRP) performed with the da Vinci Si Surgical System, comparison was performed between 30 single-port (SP group) and 26 multiport (MP group) cases. Comparisons included operative time, estimated blood loss (EBL), hospital stay, peritoneal violation, pain scores, scar satisfaction, continence, and erectile function. The median operation time and EBL were not different between the two groups. In the SP group, the median operation time of the first 10 patients was obviously longer than that of the latter 20 patients (P < 0.001). The median postoperative hospital stay in the SP group was shorter than that in the MP group (P < 0.001). The rate of peritoneal damage in the SP group was less than that in the MP group (P = 0.017). The pain score and overall need for pain medications in the SP group were lower than those in the MP group (P < 0.001 and P = 0.015, respectively). Patients in the SP group were more satisfied with their scars than those in the MP group 3 months postoperatively (P = 0.007). At 3 months, the cancer control, recovery of erectile function, and urinary continence rates were similar between the two groups. It is safe and feasible to perform epR-spRP using the da Vinci Si surgical system. Therefore, epR-spRP can be a treatment option for localized prostate cancer. Although epR-spRP still has a learning curve, it has advantages for postoperative pain and self-assessed cosmesis. In the absence of the single-port robotic surgery platform, we can still provide minimally invasive surgery for patients.


Assuntos
Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Medicina Perioperatória/instrumentação , Prostatectomia/instrumentação , Procedimentos Cirúrgicos Robóticos/normas , Idoso , Perda Sanguínea Cirúrgica/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde/métodos , Medicina Perioperatória/normas , Medicina Perioperatória/estatística & dados numéricos , Prostatectomia/métodos , Neoplasias da Próstata/cirurgia , Garantia da Qualidade dos Cuidados de Saúde/estatística & dados numéricos , Procedimentos Cirúrgicos Robóticos/métodos , Procedimentos Cirúrgicos Robóticos/estatística & dados numéricos
9.
Materials (Basel) ; 12(19)2019 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-31561493

RESUMO

2,2',7,7'-Tetrakis(N,N-di-p-methoxyphenyl-amine)-9,9'-spirobifluorene (spiro-OMeTAD) film currently prevails as hole transport layer (HTL) employed in perovskite solar cells (PSCs). However, the standard preparation method for spin-coated, Lithium bis(trifluoromethylsulfony) imide (LiTFSI)-doped, spiro-OMeTAD HTL depends on a time-consuming and uncontrolled oxidation process to gain desirable electrical conductivity to favor device operation. Our previous work demonstrated that ~10 s oxygen or oxygen containing gas discharge plasma exposure can oxidize spiro-OMeTAD HTL effectively and make PSCs work well. In this communication, hole-only devices are fabricated and in-situ current density-voltage measurements are performed to investigate the change in hole mobility of LiTFSI-doped spiro-OMeTAD films under plasma exposure. The results reveal that hole mobility values can be increased averagely from ~5.0 × 10-5 cm2V-1s-1 to 7.89 × 10-4 cm2V-1s-1 with 7 s O2 plasma exposure, and 9.33 × 10-4 cm2V-1s-1 with 9 s O2/Ar plasma exposure. The effects on the photovoltaic performance of complete PSC devices are examined, and optical emission spectroscopy (OES) is used for a diagnostic to explain the different exposure effects of O2 and O2/Ar plasma. High efficiency, fine controllability and good compatibility with current plasma surface cleaning techniques may make this method an important step towards the future commercialization of photovoltaic technologies employing spiro-OMeTAD hole transport material.

10.
Mol Clin Oncol ; 10(3): 343-351, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30847172

RESUMO

The aim of the present study was to assess the oncological and functional outcomes of testis-sparing surgery (TSS) for testicular tumors compared with radical orchiectomy (RO) in a single center. A retrospective comparative cohort study was conducted in Changzheng Hospital. Patients were identified using the hospital information system from January 1999 to December 2016, collecting all of the data regarding clinical, treatment and prognostic profiles. Patient follow-up was also executed to obtain information on patients' survival status, serum markers profiles, disease progression, androgen substitution requirement and paternity status. In total 158 patients were enrolled into the cohort study, including 23 TSS cases. The TSS procedure was primarily conducted in younger patients (average age, 31.9 vs. 47.7 years) or those with smaller tumors (average tumor diameter, 26.0 vs. 51.5 mm). The overall survival and recurrence free survival revealed no differences in the two groups, suggesting similar oncological outcomes. Kaplan-Maier analysis demonstrated a higher cumulative paternity rate in the TSS group than in RO group, indicating a possible advantage of preserving patients' fertility in TSS over RO. TSS with proper adjuvant therapies proved to be a promising alternative in the avoidance of emasculation, infertility, life-long androgen substitution and other psychosexual difficulties, as the oncological outcomes were not inferior to RO in the selected cases. However, further investigation is required in order to assess its oncological and functional values.

11.
Cell Death Dis ; 10(3): 154, 2019 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-30770799

RESUMO

Long noncoding RNAs (lncRNAs) are implicated in renal cell carcinoma (RCC), but remain largely unclear. Using publicly available transcriptome sequencing data from renal cancer (n = 703) and integrating bioinformatics analyses, we screened and identified a valuable lncRNA, EGFR-AS1. In our validation cohort (n = 204), EGFR-AS1 was significantly upregulated in RCC tissues (P < 0.001). Gain-of-function and loss-of-function studies showed that EGFR-AS1 promoted cell proliferation and invasion in vitro and in vivo. Based on previous studies and sequence complementarity of EGFR with EGFR-AS1, we demonstrated that EGFR-AS1 directly bound to EGFR mRNA and inhibited its degradation. Furthermore, RNA pull-down and mass spectrometry analyses showed that EGFR-AS1 interacted with HuR, which was responsible for the mRNA stability of EGFR. Multivariate analysis suggested that higher EGFR-AS1 expression predicted a poor prognosis in RCC patients (high vs low: P = 0.018, HR = 2.204, 95% CI: 1.145-4.241). In conclusion, EGFR-AS1 enhances the malignant phenotype of RCC cells by enhancing HuR-mediated mRNA stability of EGFR. Our data also provide biological rationales for EGFR-AS1 as a prognostic biomarker and a potential therapeutic target for RCC.


Assuntos
Carcinoma de Células Renais/metabolismo , Proliferação de Células/genética , Proteína Semelhante a ELAV 1/metabolismo , Neoplasias Renais/metabolismo , Estabilidade de RNA/genética , RNA Longo não Codificante/genética , RNA Mensageiro/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/patologia , Linhagem Celular Tumoral , Receptores ErbB/genética , Receptores ErbB/metabolismo , Feminino , Seguimentos , Técnicas de Silenciamento de Genes , Humanos , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Metástase Neoplásica/genética , Prognóstico , Interferência de RNA , Taxa de Sobrevida , Transfecção , Regulação para Cima
12.
Oncogene ; 38(6): 881-895, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30177838

RESUMO

CXC chemokine receptor 4 (CXCR4) has been suggested to play a critical role in cancer metastasis. Some studies have described CXCR4 nuclear localization in metastatic lesions of renal cell carcinoma (RCC), which has been suggested to be correlated with cancer metastasis. However, the underlying mechanism and clinical significance of CXCR4 nuclear localization remains unknown. Here, we show that CXCR4 nuclear localization is more likely to occur in RCC tissues, especially in metastases, and is associated with poor prognosis. CXCR4 nuclear localization requires its nuclear localization sequence (NLS, residues 146-RPRK-149). After the mutation of NLS in CXCR4, CXCR4 nuclear localization in RCC cells is lost. Nuclear localization of CXCR4 promoted RCC tumorigenicity both in vitro and in vivo. Mechanistically, we found that CXCR4 and hypoxia-inducible factor-1α (HIF-1α) colocalized in RCC cells and interacted with each other. Moreover, CXCR4 nuclear localization promoted nuclear accumulation of HIF-1α, thereby promoting the expression of genes downstream of HIF-1α. Reciprocally, nuclear HIF-1α promoted CXCR4 transcription, thus forming a feed-forward loop. Subcellular CXCR4 and HIF-1α expression levels were independent adverse prognostic factors and could be combined with TNM stage to generate a predictive nomogram of the clinical outcome of patients with RCC. Therefore, our findings indicate that CXCR4 nuclear translocation plays a critical role in RCC metastasis and may serve as a prognostic biomarker and potential therapeutic target.


Assuntos
Carcinoma de Células Renais/metabolismo , Núcleo Celular/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Neoplasias Renais/metabolismo , Proteínas de Neoplasias/metabolismo , Receptores CXCR4/metabolismo , Transporte Ativo do Núcleo Celular/genética , Animais , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Linhagem Celular Tumoral , Núcleo Celular/genética , Núcleo Celular/patologia , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Neoplasias Renais/genética , Neoplasias Renais/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Metástase Neoplásica , Proteínas de Neoplasias/genética , Receptores CXCR4/genética
13.
Oncotarget ; 8(44): 76189-76203, 2017 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-29100303

RESUMO

Keratin 8 (KRT8) plays an essential role in the development and metastasis of multiple human cancers. However, its role in clear cell renal cell carcinoma (ccRCC) remains unexplored. Here, we investigated the expression pattern, clinical significance, and function of KRT8 in ccRCC. KRT8 mRNA and protein levels were determined in two large cohorts using quantitative real-time polymerase chain reaction (qRT-PCR) and tissue microarray (TMA) immunohistochemistry (IHC), respectively. We found that KRT8 expression was upregulated in ccRCC and vein tumor thrombi (VTTs). KRT8 overexpression in ccRCC was significantly correlated with aggressive characteristics and was predictive of a poor prognosis in ccRCC patients. Moreover, KRT8 overexpression in renal cancer cell lines promoted cell migration and invasion. In contrast, KRT8 knockdown suppressed ccRCC metastasis both in vitro and in vivo. In addition, our findings showed that KRT8 promoted ccRCC metastasis by increasing IL-11 expression, causing IL-11 autocrine induction, and triggering STAT3 signaling. Overall, this study established the significance of KRT8-IL-11 axis activation in aggressive ccRCC and defined a novel critical signaling mechanism that drives human ccRCC invasion and metastasis.

14.
Mol Cancer ; 16(1): 111, 2017 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-28659173

RESUMO

BACKGROUND: Recent evidences showed that long noncoding RNAs (lncRNAs) are frequently dysregulated and play important roles in various cancers. Clear cell renal cell carcinoma (ccRCC) is one of the leading cause of cancer-related death, largely due to the metastasis of ccRCC. However, the clinical significances and roles of lncRNAs in metastatic ccRCC are still unknown. METHODS: lncRNA expression microarray analysis was performed to search the dysregulated lncRNA in metastatic ccRCC. quantitative real-time PCR was performed to measure the expression of lncRNAs in human ccRCC samples. Gain-of-function and loss-of-function experiments were performed to investigate the biological roles of lncRNAs on ccRCC cell proliferation, migration, invasion and in vivo metastasis. RNA pull-down, RNA immunoprecipitation, chromatin immunoprecipitation, and western blot were performed to explore the molecular mechanisms underlying the functions of lncRNAs. RESULTS: The microarray analysis identified a novel lncRNA termed metastatic renal cell carcinoma-associated transcript 1 (MRCCAT1), which is highly expressed in metastatic ccRCC tissues and associated with the metastatic properties of ccRCC. Multivariate Cox regression analysis revealed that MRCCAT1 is an independent prognostic factor for ccRCC patients. Overexpression of MRCCAT1 promotes ccRCC cells proliferation, migration, and invasion. Depletion of MRCCAT1 inhibites ccRCC cells proliferation, migration, and invasion in vitro, and ccRCC metastasis in vivo. Mechanistically, MRCCAT1 represses NPR3 transcription by recruiting PRC2 to NPR3 promoter, and subsequently activates p38-MAPK signaling pathway. CONCLUSIONS: MRCCAT1 is a critical lncRNA that promotes ccRCC metastasis via inhibiting NPR3 and activating p38-MAPK signaling. Our results imply that MRCCAT1 could serve as a prognostic biomarker and therapeutic target for ccRCC.


Assuntos
Carcinoma de Células Renais/patologia , Neoplasias Renais/patologia , RNA Longo não Codificante/genética , Receptores do Fator Natriurético Atrial/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Idoso , Animais , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/mortalidade , Linhagem Celular Tumoral , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Renais/genética , Neoplasias Renais/metabolismo , Neoplasias Renais/mortalidade , Masculino , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade , Prognóstico , Regiões Promotoras Genéticas , Receptores do Fator Natriurético Atrial/genética , Transdução de Sinais , Ensaios Antitumorais Modelo de Xenoenxerto , Proteínas Quinases p38 Ativadas por Mitógeno/genética
15.
Free Radic Res ; 50(4): 454-66, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26729624

RESUMO

The present study aimed to investigate whether hyperbaric oxygen preconditioning (HBO-PC) could ameliorate hypoxia-ischemia brain damage (HIBD) by an increase of Nrf2 expression. P7 Sprague-Dawley rats (aged 7 d, n = 195) were used in two in vivo experiments, including BO-PC exposure experiments in non-HIBD models and treatment experiments in HIBD models. 2,3,5-triphenyltetrazolium chloride (TTC) staining, Nissl Staining, and TUNEL staining were performed. And expressions of Nrf2, HO-1, and GSTs were measured. For in vitro studies, oxygen-glucose deprivation cells were established. Morphological and apoptotic staining and gene silencing of Nrf2 by siRNA transfection were investigated. For exposure experiments, HBO-PC for longer time increased the expression of Nrf2 significantly. And for treatment experiments, HBO-PC treatment significantly decreased infarction area, lessened neuronal injury, reduced apoptosis, and increased both the expression of Nrf2 and activities of its downstream proteins. Cytology tests confirmed effects of HBO-PC treatments. Besides, Nrf2 siRNA significantly reduced protective effects of HBO-PC. These observations demonstrated that an up-regulation of Nrf2 by HBO-PC might play an important role in the generation of tolerance against HIBD.


Assuntos
Oxigenoterapia Hiperbárica , Hipóxia Encefálica/terapia , Hipóxia-Isquemia Encefálica/terapia , Fator 2 Relacionado a NF-E2/agonistas , Oxigênio/farmacologia , Animais , Animais Recém-Nascidos , Apoptose/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/patologia , Feminino , Regulação da Expressão Gênica , Glucose/deficiência , Glucose/farmacologia , Glutationa Transferase/genética , Glutationa Transferase/metabolismo , Heme Oxigenase (Desciclizante)/genética , Heme Oxigenase (Desciclizante)/metabolismo , Hipóxia Encefálica/genética , Hipóxia Encefálica/metabolismo , Hipóxia Encefálica/patologia , Hipóxia-Isquemia Encefálica/genética , Hipóxia-Isquemia Encefálica/metabolismo , Hipóxia-Isquemia Encefálica/patologia , Masculino , Fator 2 Relacionado a NF-E2/antagonistas & inibidores , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Cultura Primária de Células , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais
16.
Free Radic Biol Med ; 65: 731-741, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23954468

RESUMO

Molecular hydrogen has been proven effective in ameliorating cerebral ischemia/reperfusion (I/R) injury by selectively neutralizing reactive oxygen species. Lactulose can produce a considerable amount of hydrogen through fermentation by the bacteria in the gastrointestinal tract. To determine the neuroprotective effects of lactulose against cerebral I/R injury in rats and explore the probable mechanisms, we carried out this study. The stroke model was produced in Sprague-Dawley rats through middle cerebral artery occlusion. Intragastric administration of lactulose substantially increased breath hydrogen concentration. Behavioral and histopathological verifications matched biochemical findings. Behaviorally, rats in the lactulose administration group won higher neurological scores and showed shorter escape latency time in the Morris test. Morphologically, 2,3,5-triphenyltetrazolium chloride showed smaller infarction volume; Nissl staining manifested relatively clear and intact neurons and TUNEL staining showed fewer apoptotic neurons. Biochemically, lactulose decreased brain malondialdehyde content, caspase-3 activity, and 3-nitrotyrosine and 8-hydroxy-2-deoxyguanosine concentration and increased superoxide dismutase activity. The effects of lactulose were superior to those of edaravone. Lactulose orally administered activated the expression of NF-E2-related factor 2 (Nrf2) in the brain as verified by RT-PCR and Western blot. The antibiotics suppressed the neuroprotective effects of lactulose by reducing hydrogen production. Our study for the first time demonstrates a novel therapeutic effect of lactulose on cerebral ischemia/reperfusion injury and the probable underlying mechanisms. Lactulose intragastrically administered possessed neuroprotective effects on cerebral I/R injury in rats, which could be attributed to hydrogen production by the fermentation of lactulose through intestinal bacteria and Nrf2 activation.


Assuntos
Isquemia Encefálica/metabolismo , Hidrogênio/metabolismo , Lactulose/farmacologia , Fator 2 Relacionado a NF-E2/metabolismo , Fármacos Neuroprotetores/farmacologia , Traumatismo por Reperfusão/metabolismo , Animais , Western Blotting , Encéfalo/efeitos dos fármacos , Imuno-Histoquímica , Marcação In Situ das Extremidades Cortadas , Lactulose/metabolismo , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Fármacos Neuroprotetores/metabolismo , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase em Tempo Real
17.
Dig Dis Sci ; 58(6): 1560-8, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23371012

RESUMO

BACKGROUND: Molecular hydrogen (H2) is a potent antioxidant and able to protect organs from oxidative stress injuries. Orally administered lactulose, a potent H2 inducer, is digested by colon microflora and significantly increases H2 production, indicating its potential anti-inflammatory action. OBJECTIVE: To evaluate the anti-inflammatory effects of lactulose on dextran sodium sulfate (DSS)-induced colitis in mice. METHODS: Mice were randomly assigned into seven groups, receiving regular distilled water, H2-rich saline (peritoneal injection), DSS, oral lactulose (0.1, 0.15, 0.2 ml/10 g, respectively), and lactulose (0.2 ml/10 g) + oral antibiotics. The mouse model of human ulcerative colitis was established by supplying mice with water containing DSS. The H2 breath test was used to determine the exhaled H2 concentration. Body weight, colitis score, colon length, pathological features and tumor necrosis factor alpha (TNF-α), interleukin-1ß (IL-1ß), maleic dialdehyde (MDA) and marrow peroxidase (MPO) levels in colon lesions were evaluated. RESULTS: After 7 days, DSS-induced loss of body weight, increase of colitis score, shortening of colon length, pathological changes and elevated levels of TNF-α, IL-1ß, MDA, and MPO in colon lesions, were significantly suppressed by oral lactulose administration and intraperitoneally injected H2-rich saline. Ingestion of antibiotics significantly compromised the anti-inflammatory effects of lactulose. The H2 breath test showed that lactulose administration significantly induced hydrogen production and that antibiotics administration could inhibit H2 production. CONCLUSION: Lactulose can prevent the development of DSS-induced colitis and alleviate oxidative stress in the colon, as measured by MDA and MPO, probably by increasing endogenous H2 production.


Assuntos
Colite/tratamento farmacológico , Fármacos Gastrointestinais/uso terapêutico , Lactulose/uso terapêutico , Administração Oral , Animais , Antibacterianos/administração & dosagem , Antibacterianos/farmacologia , Biomarcadores/metabolismo , Testes Respiratórios , Colite/induzido quimicamente , Colite/metabolismo , Colite/microbiologia , Colo/efeitos dos fármacos , Colo/metabolismo , Colo/patologia , Sulfato de Dextrana , Esquema de Medicação , Fármacos Gastrointestinais/farmacologia , Hidrogênio/metabolismo , Lactulose/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Estresse Oxidativo/efeitos dos fármacos , Distribuição Aleatória
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