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1.
Mol Med Rep ; 29(6)2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38666533

RESUMO

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that certain of the Transwell cell invasion and migration assay data shown in Fig. 2D and F on p. 3786 were strikingly similar to data appearing in different form in other articles written by different authors at different research institutes, which had already been published. Owing to the fact that the contentious data in the above article had already been published prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 20: 3782­3792, 2019; DOI: 10.3892/mmr.2019.10636].

2.
Front Neurol ; 14: 1191831, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37928141

RESUMO

Objective: To investigate the clinical variables that might predict the outcome of developmental and epileptic encephalopathy (DEE) after vagus nerve stimulation (VNS) therapy and identify the risk factors for poor long-term outcome. Patients and methods: We retrospectively studied 32 consecutive children with drug-resistant DEE who had undergone VNS surgery from April 2019 to July 2021, which were not suitable for corpus callosotomy. In spite of combining valproic acid, levetiracetam, lamotrigine, topiramate, etc. (standard anti-seizure medicine available in China) it has not been possible to effectively reduce seizures in the population we investigate (Cannabidiol and brivaracetam were not available in China). A responder was defined as a frequency reduction decrease > 50%. Seizure freedom was defined as freedom from seizures for at least 6 months. Sex, electroencephalograph (EEG) group, neurodevelopment, time lag, gene mutation, magnetic resonance imaging (MRI), and epilepsy syndrome were analyzed with Fisher's exact test, The age at onset and age at VNS therapy were analyzed with Kruskal-Wallis test, statistical significance was defined as p < 0.05. And used the effect size to correction. Results: Among the 32 patients, the median age at VNS implantation was 4.7 years (range: 1-12 years). At the most recent follow-up, five children (15.6%) were seizure-free and 22 (68.8%) were responders. Univariate analysis demonstrated that the responders were significantly associated with mild development delay/intellectual disability (p = 0.044; phi coefficient = 0.357) and a multifocal EEG pattern (p = 0.022; phi coefficient = -0.405). Kaplan-Meier survival analyses demonstrated that a multifocal EEG pattern (p = 0.049) and DEE without epileptic spasm (ES) (p = 0.012) were statistically significant (p = 0.030). Multivariate analysis demonstrated that DEE with ES had significant predictive value for poor long-term outcome (p = 0.014, hazard ratio = 5.433, confidence interval = 1.402-21.058). Conclusions: Our study suggested that VNS was a generally effective adjunct treatment for DEE. Although the predictive factors for VNS efficacy remain unclear, it should be emphasized that patients with ES are not suitable candidates for epilepsy surgery. Further investigations are needed to validate the present results.

3.
BMC Cancer ; 23(1): 941, 2023 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-37798689

RESUMO

BACKGROUND: Inflammatory, immune, and nutritional status are key factors in obstructive colorectal cancer (OCRC). This study aims to investigate the value of modified Naples prognostic score (M-NPS) in evaluating OCRC prognosis. METHODS: A total of 196 OCRC patients were retrospectively analyzed to construct M-NPS based on serum albumin (ALB), total cholesterol (CHOL), neutrophil:lymphocyte ratio (NLR), and lymphocyte:monocyte ratio (LMR), and then they were divided into three groups. The Kaplan-Meier (KM) method and Cox proportional hazard regression analysis were performed for overall survival (OS) and disease-free survival (DFS) of OCRC patients. RESULTS: Patients with high M-NPS had worse OS and DFS (P = 0.0001, P = 0.0011). Multivariate COX analysis showed that M-NPS was an independent prognostic factor for OCRC patients. Patients in the M-NPS 2 group had significantly worse OS (hazard ratio [HR] = 4.930 (95% confidence interval [95% CI], 2.217-10.964), P < 0.001) and DFS (HR = 3.508 (95% CI, 1.691-7.277), P < 0.001) than those in the 0 group. CONCLUSION: M-NPS was an independent prognostic factor for OCRC patients; it might provide a potential reference for immunonutritional intervention in patients with obstruction.


Assuntos
Neoplasias Colorretais , Linfócitos , Humanos , Prognóstico , Estudos Retrospectivos , Intervalo Livre de Doença
4.
Anal Chim Acta ; 1278: 341709, 2023 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-37709452

RESUMO

Gold nanoparticles (AuNPs) with localized surface plasmon resonance effect have been widely used for colorimetric detection based on the interparticle plasmon coupling during AuNPs aggregation. However, it is still challenging to develop portable and quantitative methods with good sensitivity and excellent selectivity. In this study, a smartphone-based colorimetric assay is developed on the principle of surfactant-mediated AuNPs aggregation assisted with rolling circle amplification (RCA) on magnetic beads (MBs). The detection of adenosine is demonstrated as an example. The cetyl trimethyl ammonium bromide (CTAB) causes the negatively charged AuNPs to aggregate, which results in the color change from red to blue. When adenosine is in solution, the RCA process is triggered on the MBs because of specific adenosine-aptamer recognition, resulting in prolongation of single-stranded nucleic acid (ssDNA). The solution color remains red due to the electrostatic interaction between CTAB and ssDNA. Using this method, the limit of detection (LOD) for adenosine can be as low as 16 pM. Besides, it also works well in human serum. In addition, a portable device integrated with in-situ RGB analysis software is developed for the detection with a smartphone. This study offers a new strategy to improve the sensitivity and selectivity for the AuNPs-based colorimetric assay, taking advantages of specific aptamer recognition, in-situ RCA on MBs, magnetic separation, and smartphone-based portable device.


Assuntos
Nanopartículas Metálicas , Ácidos Nucleicos , Humanos , Tensoativos , Colorimetria , Ouro , Cetrimônio , Lipoproteínas , Adenosina , Oligonucleotídeos , Fenômenos Magnéticos
5.
Chin J Physiol ; 66(3): 171-180, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37322627

RESUMO

Long non-coding RNAs (lncRNAs) are important players in cancer development. LncRNA FGD5-AS1 has been reported as a potential oncogene in ovarian cancer (OC). The present paper focused on the action mechanism of FGD5-AS1 in OC. Clinical OC samples were collected for expression analyses of FGD5-AS1, RBBP6, and miR-107. The expression of FGD5-AS1, RBBP6, and miR-107 in OC cells was altered by transfection. OC cell proliferation was assessed by MTT and colony formation assays, and angiogenesis of human umbilical vein endothelial cells (HUVECs) cultured with OC cell supernatants by matrigel angiogenesis assay. The interactions among FGD5-AS1, miR-107, and RBBP6 were detected by luciferase reporter assay. FGD5-AS1 and RBBP6 were strongly expressed and miR-107 was poorly expressed in clinical OC samples and OC cell lines. FGD5-AS1 or RBBP6 overexpression in Hey and SKOV3 cells could potentiate OC cell proliferation and HUVEC angiogenesis, while FGD5-AS1 or RBBP6 knockdown in OC cells inhibited the above cellular processes. FGD5-AS1 targeted miR-107 to positively regulate RBBP6 expression. Additionally, miR-107 overexpression or RBBP6 knockdown in SKOV3 cells partially reversed the FGD5-AS1-dependent stimulation of OC cell proliferation and HUVEC angiogenesis. FGD5-AS1 may act as a promoter of OC via miR-107/RBBP6 axis.


Assuntos
MicroRNAs , Neoplasias Ovarianas , RNA Longo não Codificante , Humanos , Feminino , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Células Endoteliais/metabolismo , Regulação Neoplásica da Expressão Gênica , Linhagem Celular Tumoral , Neoplasias Ovarianas/genética , Proliferação de Células , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Fatores de Troca do Nucleotídeo Guanina/genética , Fatores de Troca do Nucleotídeo Guanina/metabolismo
6.
Anal Chem ; 94(11): 4643-4649, 2022 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-35258931

RESUMO

Hyaluronidase (HAase) is implicated in inflammation, cancer development, and allergic reaction. The detection of HAase is significantly important in clinical diagnosis and medical treatment. Herein, we propose a new principle for the development of equipment-free and label-free paper-based flow sensors based on the enzymatic hydrolysis-induced viscosity change in a stimuli-responsive polymer solution, which increases the water flow distance on the pH indicator paper. The detection of HAase is demonstrated as an example. This facile and versatile method can overcome the potential drawbacks of traditional hydrogel-based sensors, including complex preparation steps, slow response time, or low sensitivity. Moreover, it can also avoid the use of specialized instruments, labeled molecules, or functionalized nanoparticles in the sensors developed using the polymer solutions. Using this strategy, the detection of HAase is achieved with a limit of detection as low as 0.2 U/mL. Also, it works well in human urine. Additionally, the detection of tannic acid, which is an inhibitor of HAase, is also fulfilled. Overall, a simple, efficient, high-throughput, and low-cost detection method is developed for the rapid and quantitative detection of HAase and its inhibitor without the use of labeled molecules, synthetic particles, and specialized instruments. As only minimal reagents of HAase, HA, and paper are used, it is very promising in the development of commercial kits for point-of-care testing.


Assuntos
Hialuronoglucosaminidase , Polímeros , Humanos , Ácido Hialurônico/química , Hialuronoglucosaminidase/urina , Hidrólise , Viscosidade
7.
Ir J Med Sci ; 191(4): 1555-1560, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34467471

RESUMO

BACKGROUND: Renal cell carcinoma or RCC is a type of malignancy commonly occurred in the human kidney especially in the adults. The pathogenesis of RCC involves the complex networking of multiple signaling pathways, and the underlying molecular mechanisms remain largely unclear. OBJECTIVES: This study aimed to elucidate the regulatory functions of UBA2 and explore its potential downstream molecules during the tumor progression in RCC. METHODS: In this paper, the expression of UBA2 and associated molecules was examined by RT-qPCR and western blotting. The proliferative activity of RCC cells was determined using CCK-8 assay and immunofluorescence staining of proliferation-related marker Ki-67. Moreover, the cell distribution and apoptosis were evaluated by flow cytometry. RESULTS: Our results revealed the upregulation of UBA2 in RCC tissues and cells, and the high-expression of UBA2 was also associated with bigger tumor size, more advanced stage, and poorer overall survival in RCC patients. In addition, UBA2 knockdown was able to suppress the growth of RCC cells and induced cell cycle arrest at G0/G1 phase. Furthermore, the p53 signaling could be the novel target of UBA2 in RCC, and UBA2 affected the biological behaviors of RCC cells in a p53-dependent manner. CONCLUSION: In summary, UBA2 was able to enhance the proliferation, inhibit the apoptosis, and suppress cell cycle arrest in RCC cells by targeting the p53 pathway.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Proteína Supressora de Tumor p53 , Enzimas Ativadoras de Ubiquitina , Adulto , Apoptose , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Pontos de Checagem do Ciclo Celular , Linhagem Celular Tumoral , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Renais/genética , Neoplasias Renais/patologia , Proteína Supressora de Tumor p53/metabolismo , Enzimas Ativadoras de Ubiquitina/metabolismo
8.
J Bone Miner Res ; 36(10): 1931-1941, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34173271

RESUMO

Bizarre parosteal osteochondromatous proliferation (BPOP), or Nora's lesion, is a rare benign osteochondromatous lesion. At present, the molecular etiology of BPOP remains unclear. JMJD3(KDM6B) is an H3K27me3 demethylase and counteracts polycomb-mediated transcription repression. Previously, Jmjd3 was shown to be critical for bone development and osteoarthritis. Here, we report that conditional deletion of Jmjd3 in chondrogenic cells unexpectedly resulted in BPOP-like lesion in mice. Biochemical investigations revealed that Jmjd3 inhibited BPOP-like lesion through p16Ink4a . Immunohistochemistry and RT-qPCR assays indicated JMJD3 and p16INK4A level were significantly reduced in human BPOP lesion compared with normal subjects. This was further confirmed by Jmjd3/Ink4a double-gene knockout mice experiments. Therefore, our results indicated the pathway of Jmjd3/p16Ink4a may be essential for the development of BPOP in human. © 2021 American Society for Bone and Mineral Research (ASBMR).


Assuntos
Neoplasias Ósseas , Osteocondroma , Animais , Proliferação de Células , Inibidor p16 de Quinase Dependente de Ciclina/genética , Camundongos , Osteocondroma/genética , Transdução de Sinais
9.
Anticancer Drugs ; 32(3): 269-277, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33491971

RESUMO

Long-chain noncoding RNAs (lncRNAs) are involved in a wide range of biological and pathological processes in ovarian cancer. The purpose of this study was to investigate the effects of EZH2-mediated ABHD11-AS1 promoter on the pathogenesis of ovarian cancer. The expression levels of EZH2, ABHD11-AS1 and miR-133a-3p were examined in ovarian cancer tissues using reverse transcription-quantitative PCR. Cell proliferation was evaluated using cell counting kit 8 assay, and cell invasion/migration was determined using a Transwell assay. Cell apoptosis was evaluated using flow cytometry. Dual luciferase assay was performed to confirm the interaction between ABHD11-AS1 and miR-133a-3p. The binding site of H3K27me3 on ABHD11-AS1 promoter was confirmed by ChIP. The expression of ABHD11-AS1 was significantly upregulated in ovarian cancer samples, and its levels were closely associated with lymph node metastasis, tumor stage and 3-year survival rate. Furthermore, interference of ABHD11-AS1 suppressed the proliferation, migration and invasion of ovarian cancer cells, while cell apoptosis was promoted. Additionally, miR-133a-3p could be a novel target of ABHD11-AS1, and EZH2-mediated H3K27me3 protein might bind to ABHD11-AS1 promoter directly. Moreover, rescue experiments indicated that the effects caused by ABHD11-AS1 knockdown on the malignant characteristics of ovarian cancer cells were notably enhanced by miR-133a-3p mimics, whereas the influences on cell growth and metastasis induced by overexpressed ABHD11-AS1 were abrogated by the restoration of miR-133a-3p expression. In summary, EZH2-mediated enrichment of H3K27me3 on ABHD11-AS1 promoter could regulate the progression of ovarian cancer via miR-133a-3p. Therefore, EZH2/ABHD11-AS1/miR-133a-3p axis might be a putative candidate for targeted treatment of ovarian cancer.


Assuntos
Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Neoplasias Ovarianas/patologia , RNA Longo não Codificante/metabolismo , Serina Proteases/metabolismo , Adulto , Idoso , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Humanos , Metástase Linfática/patologia , MicroRNAs , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Ovarianas/mortalidade
10.
Nutr Cancer ; 73(9): 1657-1667, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32924631

RESUMO

OBJECTIVE: Previous studies have investigated the pretreatment prognostic nutritional index (PNI) as a prognostic factor in patients with nasopharyngeal carcinoma (NPC); however, the results remained inconsistent. We aimed to assess the prognostic value of PNI in patients with NPC through conducting meta-analysis. Methods: Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated for low PNI of overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS), loco-regional recurrence-free survival (LRFS), and cancer-specific survival (CSS). Results: Totally, eight studies involving 4299 patients were included in this meta-analysis. A low pretreatment PNI was associated with poor OS (HR = 1.86, 95% CI = 1.55-2.33, P < 0.001), DMFS (HR = 2.03, 95% CI = 1.69-2.44, P < 0.001), PFS (HR = 1.57, 95% CI = 1.31-1.90, P < 0.001), and CSS (HR = 2.29, 95% CI = 1.54-3.42, P < 0.001). The subgroup analysis showed that low PNI remained a significant factor for poor OS, DMFS, and PFS irrespective of treatment, country, and cutoff value of PNI. In addition, low PNI was correlated to female gender (OR = 1.35, 95% CI = 1.12-1.62, P = 0.002), older age (OR = 1.75, 95% CI = 1.17-2.62, P = 0.007), and T3-T4 stage (OR = 1.27, 95% CI = 1.06-1.53, P = 0.011). Conclusions: A low PNI was associated with poor survival outcomes in patients with NPC. Moreover, PNI could serve as an index to help guide clinical management for older patients.


Assuntos
Neoplasias Nasofaríngeas , Avaliação Nutricional , Idoso , Feminino , Humanos , Carcinoma Nasofaríngeo , Prognóstico , Modelos de Riscos Proporcionais
11.
Mol Med Rep ; 22(6): 4810-4820, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33173957

RESUMO

Renal cell carcinoma (RCC) is a common type of malignancy in the kidney, which accounts for ~80% of the cases within adult patients. The pathogenesis of RCC is complicated and involves alterations at both genetic and epigenetic levels. The aim of the present study was to investigate the roles of circRNAs in the pathogenesis of RCC. In the current study, exosomes were isolated via gradient centrifugation and identified using transmission electron microscope. The expression levels of circular RNA (circ)_400068, microRNA (miR)­210­5p and suppressor of cytokine signaling 1 (SOCS1) were examined using reverse transcription­quantitative PCR. Cell proliferation was evaluated using a Cell Counting Kit­8 assay, and the apoptotic rate was determined in transfected cells using flow cytometry. The protein expression levels of proliferation­ and apoptosis­associated genes were assessed via western blot analysis. Upregulation of circ_400068 was detected in RCC plasma exosomes, tissue samples and cells. Additionally, treatment with exosomal circ_400068 promoted the proliferation and inhibited the apoptosis of healthy kidney cells, which were abrogated by short hairpin RNA­circ_400068. The results suggested that miR­210­5p was a potential downstream molecule of circ_400068, and SOCS1 was a novel target of miR­210­5p. Moreover, circ_400068 regulated the proliferation of HK­2 cells by targeting the miR­210­5p/SOCS1 axis, as the effects on cell proliferation caused by treatment using exosomes isolated from the culture media of RCC cells were abolished by miR­210­5p mimics. It was found that enhanced cell proliferation induced by miR­210­5p inhibitors was attenuated by the knockdown of SOCS1, while the influences triggered by miR­210­5p mimics were reversed by SOCS1 overexpression. Collectively, the present findings provided a novel insight into the crucial regulatory functions of circ_400068 in RCC, and the circ_400068/miR­210­5p/SOCS1 axis could be a candidate therapeutic target for the treatment of patients with RCC.


Assuntos
Carcinoma de Células Renais/genética , Exossomos/metabolismo , RNA Circular/genética , Adulto , Idoso , Apoptose/genética , Carcinoma de Células Renais/metabolismo , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Neoplasias Renais/genética , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Proteína 1 Supressora da Sinalização de Citocina/genética , Proteína 1 Supressora da Sinalização de Citocina/metabolismo , Proteínas Supressoras da Sinalização de Citocina/genética
12.
FASEB J ; 34(5): 7144-7159, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32275117

RESUMO

Disrupted mitochondrial function and reactive oxygen species (ROS) generation cause cellular damage and oxidative stress-induced macrophage inflammatory cell death. It remains unclear how mitochondrial dysfunction relates to inflammasome activation and pyroptotic cell death. In this study, we demonstrated that tumor necrosis factor receptor-associated factor 3 (TRAF3) regulates mitochondrial ROS production and promotes TLR agonist LPS plus nigericin (LPS/Ng)-induced inflammasome and pyroptosis in mouse primary macrophages and human monocyte THP-1 cells. Co-IP assays confirmed that TRAF3 forms a complex with TRAF2 and cIAP1 and mediates ubiquitin and degradation of Unc-51 like autophagy activating kinase 1 (ULK1). Moreover, knockdown of ULK1 in THP-1 cells significantly promoted LPS/Ng-induced inflammasome by activating caspase 1 and mature IL-1ß. Apoptosis inducing factor (AIF) translocation from mitochondrial to nuclear was observed in ULK1-deficient THP-1 cells under LPS/Ng stimulation, which mediates LPS/Ng-induced cell death in ULK1 deficient macrophages. In conclusion, this study identified a novel role of TRAF3 in regulation of ULK1 ubiquitination and inflammasome signaling and provided molecular mechanisms by which ubiquitination of ULK1 controls mitochondrial ROS production, inflammasome activity, and AIF-dependent pyroptosis.


Assuntos
Proteína Homóloga à Proteína-1 Relacionada à Autofagia/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Macrófagos/metabolismo , Fator 3 Associado a Receptor de TNF/metabolismo , Animais , Proteína Homóloga à Proteína-1 Relacionada à Autofagia/deficiência , Proteína Homóloga à Proteína-1 Relacionada à Autofagia/genética , Células Cultivadas , Técnicas de Silenciamento de Genes , Humanos , Inflamassomos/metabolismo , Proteínas Inibidoras de Apoptose/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/deficiência , Peptídeos e Proteínas de Sinalização Intracelular/genética , Lipopolissacarídeos/farmacologia , Macrófagos/citologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Modelos Biológicos , Monócitos/citologia , Monócitos/metabolismo , Nigericina/farmacologia , Piroptose/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Células THP-1 , Fator 3 Associado a Receptor de TNF/deficiência , Fator 3 Associado a Receptor de TNF/genética , Ubiquitinação/efeitos dos fármacos
13.
Mol Med Rep ; 20(4): 3782-3792, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31485634

RESUMO

Renal cell carcinoma (RCC) is the most common kidney malignancy, responsible for ~80% of all cases in adults. The pathogenesis of RCC is complex, involving alterations at both the genetic and epigenetic levels. Numerous signaling pathways, such as PI3K/Akt/mTOR and Wnt­ß­catenin have been demonstrated to be associated with the tumorigenesis and development of RCC. Long non­coding RNAs (lncRNAs) are functional RNA molecules involved in the initiation and progression of cancer, and investigating the effects of lncRNA could facilitate the development of novel treatments. The lncRNA regulator of reprogramming (ROR) is aberrantly expressed in a variety of tumors. However, its underlying mechanisms remain largely unknown. In the present study, ROR was found to be upregulated and microRNA (miR)­206 was found to be downregulated in RCC tissues and cells. Furthermore, the knockdown of ROR inhibited the proliferation, migration and invasion of RCC cells. It was found that ROR binds to miR­206, and that ROR­induced cell proliferation and metastasis were reversed by the overexpression of miR­206. In addition, the levels of miR­206 and ROR were negatively correlated in RCC tissues. Furthermore, the overexpression of miR­206 notably suppressed the proliferation, migration and invasion of RCC cells, and these effects were enhanced by the knockdown of vascular endothelial growth factor (VEGF); cell growth and metastasis induced by miR­206 inhibitors could be reversed by the knockdown of VEGF. In addition, the expression levels of miR­206 and VEGF were inversely correlated in RCC samples. In summary, the results of the present study revealed that ROR was upregulated in RCC tissues, which promoted tumor progression by regulating the miR­206/VEGF axis. The present findings provided a novel insight into the potential functions of ROR in RCC, and the ROR/miR­206/VEGF pathway may be a promising therapeutic target for the treatment of patients with RCC.


Assuntos
Carcinoma de Células Renais/genética , Neoplasias Renais/genética , MicroRNAs/genética , RNA Longo não Codificante/genética , Fator A de Crescimento do Endotélio Vascular/genética , Adulto , Carcinoma de Células Renais/patologia , Linhagem Celular Tumoral , Progressão da Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade
14.
Anticancer Agents Med Chem ; 19(10): 1253-1261, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30947677

RESUMO

BACKGROUND: Coumarins are a wide group of naturally occurring compounds which exhibit a wide range of biological properties such as anti-cancer activities. Here, we characterized the biological functions of three Triphenylethylene-Coumarin Hybrids (TCHs) both in cell culture and nude mouse model. METHODS: Cell proliferation assay was performed in the cell cultures of both EA.hy926 endothelial cell and breast cancer cell lines treated with different concentrations of compound TCH-10b, TCH-5a and TCH-5c. Flowcytometry assay and Western blotting were used to further investigate the effect and mechanism of TCH-5c on EA.hy926 cell proliferation and cell cycle. The effects of TCH-5c on endothelial cell migration and angiogenesis were determined using cytoskeleton staining, migration assay and tube formation assay. Inhibition of breast cancer cell line derived VEGF by TCH-5c was shown through ELISA and the use of conditioned media. SK-BR-3 xenograft mouse model was established to further study the anti-tumorigenic role of compound TCH-5c in vivo. RESULTS: We found that compound TCH-5c has inhibitory effects on both vascular endothelial cells and breast cancer cell lines. Compound TCH-5c inhibited proliferation, resulted in cell death, increased p21 protein expression to induce G0/G1 arrest and changed endothelial cell cytoskeleton organization and migration in EA.hy926 endothelial cells. Compound TCH-5c also inhibited breast cancer cell line derived VEGF secretion, decreased breast cancer cell-induced endothelial cell tube formation in vitro and suppressed SK-BR-3 breast cancer cell-initiated tumor formation in vivo. CONCLUSION: Our study demonstrates that the coumarin derivative TCH-5c exerts its anti-cancer effects by 1. inhibiting endothelial cell proliferation, migration. 2. suppressing tube formation and angiogenesis induced by breast cancer cells in vitro and in vivo. Our results have potential implications in developing new approaches against breast cancer.


Assuntos
Inibidores da Angiogênese/química , Antineoplásicos/química , Neoplasias da Mama/irrigação sanguínea , Neoplasias da Mama/tratamento farmacológico , Carcinogênese/efeitos dos fármacos , Cumarínicos/química , Neovascularização Patológica/tratamento farmacológico , Estilbenos/química , Inibidores da Angiogênese/farmacologia , Animais , Antineoplásicos/farmacologia , Cumarínicos/farmacologia , Feminino , Humanos , Camundongos Nus , Estilbenos/farmacologia
15.
Int J Biometeorol ; 62(12): 2131-2138, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30244320

RESUMO

Low light is a type of abiotic stress that seriously affects plant growth and production efficiency. We investigated the response mechanisms of summer maize to low light by measuring the changes in endogenous hormones in the grains and during grain filling in summer maize at different light intensities to provide a theoretical basis for the production and management of summer maize under light stress. We applied different light treatments in a field experiment as follows: S, shading from tassel stage (VT) to maturity stage (R6); CK, natural lighting in the field; and L, increasing light from VT to R6. The shading level was 60%, and the maximum illumination intensity of the increasing light treatment on cloudy days was 1600-1800 µmol m-2 s-1. Compared with the control, shading significantly increased the grain abscisic acid (ABA) content at 5-20 days after pollination and decreased the indole acetic acid (IAA), zeatin riboside (ZR), and gibberellin (GA) contents (P < 0.05). The grain-filling rate decreased under shading conditions. Meanwhile, the grain volume, grain weight, and yield all decreased; the yields in 2013 and 2014 decreased by 61 and 60%, respectively. The grain IAA, ZR, and GA contents were increased by increasing light. The grain ABA content at 5-20 days after pollination did not significantly differ from that of CK (P < 0.05). After 20 days after pollination, the ABA content decreased, the grain-filling rate and the filling duration increased, and the yield increased. However, shading after anthesis increased the grain ABA content and reduced the IAA, ZR, and GA contents. Grain growth and development were inhibited, and the yield decreased. The grain ABA content decreased; the IAA, ZR, and GA contents increased; and the yield increased after increasing light. The results indicate that different light intensities regulated the levels of grains endogenous hormones, which influenced the grain-filling rate and duration, and consequently, regulated grain weight and yield.


Assuntos
Grão Comestível/efeitos da radiação , Giberelinas/metabolismo , Ácidos Indolacéticos/metabolismo , Isopenteniladenosina/análogos & derivados , Luz , Reguladores de Crescimento de Plantas/metabolismo , Zea mays/efeitos da radiação , Grão Comestível/crescimento & desenvolvimento , Grão Comestível/metabolismo , Isopenteniladenosina/metabolismo , Estações do Ano , Zea mays/crescimento & desenvolvimento , Zea mays/metabolismo
16.
Clin Neurol Neurosurg ; 171: 124-128, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29909183

RESUMO

OBJECTIVE: The aim of this study is to identify the prognostic role of MRI and EEG in posterior cortex epilepsies (PCES) and to characterize their clinical features. PATIENT AND METHODS: We retrospectively studied 54 consecutive patients (18 females, 36 males) from April 2011 to November 2015, who had undergone PCES surgery. Electro-clinical, pathological and surgical data were evaluated. Of the patients, 18 (33.3%) patients underwent a cortical resection (corticectomy), 10 (18.5%) lobectomy, 6 (11.1%) multilobar resection, 20 (30.1%) disconnection. RESULTS: The postoperative follow-up duration was ≥1 year in all patients (12-44 months, mean = 25). Thirty-two patients (59.3%) became seizure free (ILAE 1) and 40 (74.1%) had a good (ILAE 1, 2, 3) outcome. The most common pathological finding was focal cortical dysplasia (in 34 patients). Univariate analysis showed that regional scalp interictal epilepsy discharges (IEDs) (P = 0.031), Regional EEG onset (P = 0.027), a MRI lesion (P = 0.001) and the number of seizures that were recorded by the epilepsy monitor unit (P = 0.016) were significantly associated with freedom from seizures. Multivariate analysis confirmed that MRI positive was statistically significant (HR = 4.284, CI = 1.198-15.315). CONCLUSIONS: Surgical treatment is effective for PCES, and MRI and EEG analyses are important in presurgical evaluation of PCES.


Assuntos
Epilepsias Parciais/cirurgia , Epilepsia/cirurgia , Malformações do Desenvolvimento Cortical/cirurgia , Convulsões/cirurgia , Adulto , Feminino , Humanos , Masculino , Malformações do Desenvolvimento Cortical/complicações , Análise Multivariada , Período Pós-Operatório , Convulsões/complicações , Resultado do Tratamento , Adulto Jovem
17.
Oncotarget ; 8(37): 62312-62329, 2017 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-28977947

RESUMO

Tumor-infiltrating immune cells are a pivotal component of the tumor microenvironment (TME), but their indicative role remains poorly defined. A meta-analysis was performed to reveal the prognostic efficiency of tumor-infiltrating immune cells in gastric cancer (GC). By searching PubMed and Embase, we identified a total of 35 eligible articles that involved 4888 patients. Random or fixed effect models were employed to extract pooled hazard ratios (HRs) with 95% confidence intervals (CIs). Our results indicated that high CD3+ lymphocyte infiltration in all the locations (AG), the tumor nest (TN), and the tumor stroma (TS) predicted better overall survival (OS) (HR=0.71, 95% CI=0.57-0.90; HR=0.58, 95% CI=0.42-0.80; and HR=0.50, 95% CI=0.37-0.68, respectively). CD8+ T cell infiltration in AG and FoxP3+ regulatory T cells (Tregs) in the tumor invasive margin (TM) were also associated with improved OS (HR=0.90, 95% CI=0.83-0.97; HR=0.65, 95% CI=0.48-0.87, respectively). However, contrasting results were found in the macrophage subset, with M2 in AG (HR=1.45, 95% CI=1.13-1.86) and the TN (HR=1.67, 95% CI=1.12-2.48) associated with worse OS. In summary, the combination of the densities and locations of tumor-infiltrating immune cells can be useful for predicting survival for GC patients, but additional research is needed to reinforce the reliability of this study's conclusions.

18.
Mol Med Rep ; 16(6): 9561-9566, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29039528

RESUMO

Renal cell carcinoma (RCC) is one of the third most common types of urological cancer worldwide. Long non­coding RNA (lncRNA) ROR has been reported to be important in regulating the malignant activities of different types of cancer, however, the function of lncRNA ROR in RCC remains to be fully elucidated. In order to investigate the function of lncRNA ROR in RCC, reverse transcription­quantitative polymerase chain reaction (RT­qPCR) analysis was used to detect the expression of lncRNA ROR in renal cancer tissues and adjacent tissues. Cell proliferation and apoptosis were determined using Cell Counting Kit-8 and apoptosis assays. Western blot analysis was used to measure the expression levels of c­Myc and p53 following the suppression of lncRNA ROR in RCC cell lines. According to the results of the RT­qPCR analysis, lncRNA ROR was found to be expressed at high levels in RCC tissues and cell lines. Patients with RCC exhibiting high expression levels of lncRNA ROR had shorter survival rates, compared with those with low expression levels of lncRNA ROR. The knockdown of lncRNA ROR resulted in a decrease of cell proliferation and increase of apoptosis in vitro. The suppression of lncRNA ROR also induced an increase in the expression of p53 and a decrease in the expression of c­Myc in vitro. Taken together, these results demonstrated that lncRNA ROR was expressed at high levels in RCC tissue and cell lines, and was associated with the proliferation ability of RCC cells. These findings indicate that lncRNA ROR may be a promising therapeutic target for treating RCC.


Assuntos
Neoplasias Renais/genética , Neoplasias Renais/mortalidade , RNA Longo não Codificante/genética , Apoptose/genética , Ciclo Celular/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células , Feminino , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Neoplasias Renais/patologia , Masculino , Estadiamento de Neoplasias , Prognóstico , RNA Longo não Codificante/metabolismo , Análise de Sobrevida , Carga Tumoral
19.
Zhongguo Fei Ai Za Zhi ; 20(9): 610-616, 2017 Sep 20.
Artigo em Chinês | MEDLINE | ID: mdl-28935014

RESUMO

BACKGROUND: Previous reports have shown that lung cancer incidence and mortality were increasing both in male and female; however, the temporal trends in lung cancer eliminated life expectancy and potential years of life lost (PYLL) are very rare. Thus, we examine the temporal trends in lung cancer eliminated life expectancy and PYLL in Kunshan city, Jiangsu province, 1981-2015. METHODS: Data were collected from vital registry of Kunshan city. Lung cancer eliminated life expectancy and the PYLL were calculated by sex. The Chinese population in 2000 was used to calculate age-standardized PYLL. Estimate annual percentage changes (eAPC) and 95% confidence interval (CI) were used to examine the temporal trendss. RESULTS: During 1981 to 2015, substantially increasing trend was observed for the lung cancer eliminated life expectancy, which increased by 0.34 years in 1981 to 0.86 in 2015 (APC=3.2%, 95%CI: 2.8%-3.6%), and a significant increasing trend was found for male (APC=3.0%, 95%CI: 2.5%-3.5%) and female (APC=3.6%, 95%CI: 3.0%-4.2%). Moreover, the age-standardized PYLL among both sex (APC=-0.1%, 95%CI: -0.6%-0.4%) and male (APC=-0.5%, 95%CI: -1.1%-0.1%) were stable, but increasing trend was observed in females (APC=1.5%, 95%CI: 0.3%-2.7%). CONCLUSIONS: Although there was no significant change over the past 3 decades regarding the effect of premature deaths due to lung cancer, a substantial increasing trend was observed in lung cancer eliminated life expectancy, which suggested that targeted lung cancer prevention and control measures are urgently need.


Assuntos
Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/mortalidade , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , China , Intervalos de Confiança , Feminino , Humanos , Incidência , Lactente , Expectativa de Vida , Masculino , Pessoa de Meia-Idade , Adulto Jovem
20.
Epilepsy Res ; 133: 103-108, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28477458

RESUMO

OBJECTIVE: The aim of this study is to determine outcome of resective epilepsy surgery in MRI-negative extratemporal lobe epilepsy (MNETLE) patients who underwent invasive evaluations and to determine factors governing outcome. METHODS: We studied 28 patients who underwent resective epilepsy surgery for MNETLE from August 2006 to November 2015, in whom complete follow-up information was available. Electro-clinical, pathological and surgical data were evaluated. 24 patients (82.8%) were explored with intracranial EEG (9 stereoelectroencephalography (SEEG), 7 subdural grids and 8 both). All patients were followed for at least 6 months. RESULTS: During a mean follow up period of 32 [6-113] months, 13 (46.4%) patients became seizure-free (ILAE 1) and 18 (64.3%) had a good (ILAE 1, 2, 3) outcome. 21 (75.0%) patients had focal cortical dysplasia (FCD). Univariate analysis showed that more restricted (regional) interictal and ictal epileptiform discharges in surface EEG were significantly associated with seizure freedom (P=0.016 and P=0.024). Multivariate analysis confirmed that having ≥120 electrode contacts in the evaluation is an independent variable predicting seizure freedom (HR=4.283, 95% CI=1.342-13.676, P=0.014). CONCLUSION: Invasive EEG is a powerful tool in the pre-surgical evaluation of patients with MNETLE. Invasive EEG implantation that include the irritative zone and EEG onset zone as indicated by surface EEG, as well as wider brain coverage predict seizure freedom, contingent upon a sound anatomo-electro-clinical hypothesis for implantation.


Assuntos
Epilepsia/diagnóstico por imagem , Epilepsia/cirurgia , Imageamento por Ressonância Magnética , Procedimentos Neurocirúrgicos/métodos , Resultado do Tratamento , Eletroencefalografia , Feminino , Seguimentos , Humanos , Processamento de Imagem Assistida por Computador , Estimativa de Kaplan-Meier , Masculino , Oxigênio/sangue , Estudos Retrospectivos , Gravação em Vídeo
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