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Coastal estuaries are often heavily subject to riverine influences by the inputs of sediment from terrestrial sources. Hangzhou Bay (HZB) is threatened by the riverine derived trace metals from two large rivers of Qiantang River (QTR) and Yangtze River (YZR). However, previous studies mainly focused on the incidental transport from the largest river in China (YZR) and failed to simultaneously evaluate the contributions of these two rivers, especially the directly flowing river of QTR, by their trace elemental geochemical composition and distribution. Herein, a comprehensive study identified the river-derived sources of multiple trace metals in surface sediments which transported from both of the rivers. The sampling stations were separated into three regions of YZR, HZB, and QTR based on their spatial distributions of sediment grain size and components. The significant variations for most of the trace metals concentrations, except for Cd, Th, and U, were found among three regions (χ2 ≥ 8.22, p ≤ 0.016). The highest concentrations in HZB were mainly resulted from the grain size effect (68.82% of the total variance), while the highest concentrations of Sr, Cd, and Ba in YZR and Zr and Hf in QTR were attributed to the anthropogenic source (11.90%) and mineral composition (6.21%) of river basins. After normalized the diversity of multiple trace metals concentrations and the influence of grain size by ratios of Igeo and EFLi, three regions were effectively distinguished. It was indicated that As, Cd, and Sb were enriched in the sediments of rivers by anthropogenic source (EFLi > 1.5 and/or Igeo > 1). The results evidenced that, after removing the influence of grain size, elemental geochemical composition of the surface sediments confidently identified the river-derived anthropogenic sources of the enriched trace metals from two major rivers, and largely from YZR.
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Baías , Monitoramento Ambiental , Sedimentos Geológicos , Rios , Poluentes Químicos da Água , Sedimentos Geológicos/química , Sedimentos Geológicos/análise , China , Rios/química , Poluentes Químicos da Água/análise , Baías/química , Oligoelementos/análise , Metais/análiseRESUMO
Microwave (MW) dynamic therapy (MDT) can efficiently eliminate tumor residue resulting from MW thermal therapy. However, MDT is currently in its infancy, and luck of effective MDT sensiters severely limits its clinical therapeutic effect. Herein, based on TiMOF (TM), a high-efficiency MW sensitizer is designed for MW thermo-dynamic therapy. TM can generate heat and cytotoxic reacyive oxygen species (ROS) under MW irradiation and has the potential to be used as an MW sensitizer, while the suboptimal MW dynamic sensitization effect of TM limits its application. Inorder to improve the MW dynamic sensitization performance, a covalent organic framework (COF) with good stability and a large conjugate system is used to cover TM, which is conductive to electron and energy transfer, thus increasing the ROS generation rate and prolonging the ROS lifetime. In addition, loading Ni NPs endow nanomaterials with magnetic resonance imaging capabilities. Therefore, this work develops an MW sensitizer based on TM for the first time, and the mechanism of COF coating to enhance the MW dynamic sensitization of TM is preliminarily explored, which provides a new idea for the further development of MW sensitizer with great potential.
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Estruturas Metalorgânicas , Nanoestruturas , Neoplasias , Humanos , Estruturas Metalorgânicas/química , Micro-Ondas , Espécies Reativas de Oxigênio , Neoplasias/tratamento farmacológicoRESUMO
PURPOSE: The prognosis of recurrent glioblastoma (rGBM) is poor, and there is currently no effective treatment strategy. Sonodynamic therapy (SDT) is a new method for cancer treatment that uses a combination of low-frequency ultrasound and sonosensitisers to produce antitumor effects, which have shown good therapeutic effects in preclinical studies. Therefore, we initiated an open, prospective pilot study to evaluate the safety, tolerability, and efficacy of SDT for the treatment of rGBM. METHODS: Nine patients with rGBM were enrolled who had received multiple treatments, but the nidus continued to progress without additional standard treatments. After MRI localisation, porphyrin drugs were injected, and intermittent low-frequency ultrasound therapy was performed for five days. RESULTS: None of the nine patients in this clinical trial showed any clinical, neurological, haematological, or skin-targeted adverse effects associated with SDT. After the completion of the trial, one patient maintained stable disease, and eight patients experienced disease progression. Among the eight with progressive disease, the median progression-free survival time was 84 days. Four patients died, and the median overall survival duration after recurrence was 202.5 days. CONCLUSION: The number of patients in this study was small; therefore, a long-term survival benefit was not demonstrated. However, this study suggests that SDT has potential as a treatment for rGBM and warrants further exploration. Trial information: Chinese Clinical Trial Registry ( http://www.chictr.org.cn/ ): ChiCTR2200065992. November 2, 2022, retrospectively registered.
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Neoplasias Encefálicas , Glioblastoma , Humanos , Temozolomida/uso terapêutico , Glioblastoma/terapia , Glioblastoma/tratamento farmacológico , Estudos Prospectivos , Projetos Piloto , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologiaRESUMO
BACKGROUND: Hyperthermia is a widely used adjunct treatment for different cancers including nasopharyngeal carcinoma (NPC). The protooncogene c-Myc is up-regulated in NPC and its expression is associated with poor prognosis. OBJECTIVE: We hypothesized that c-Myc constitutes an important hyperthermia treatment target, and we investigated its contribution to hyperthermia responses in NPC. METHODS: The growth of the human NPC cell lines CNE1 and CNE2 was analyzed using CCK-8 and clonogenicity assays after 43 °C hyperthermia, knockdown or overexpression of c-Myc. Flow cytometry measurements assessed cell cycle parameters and apoptosis, while levels of c-Myc together with key transcriptional targets were determined using qPCR and Western blotting. Parallel experiments were undertaken using NPC xenografts in nude mice and lastly, global transcriptomic changes were determined using 'RNAseq'. RESULTS: Hyperthermia increased the ubiquitination and proteasomal destruction of c-Myc, causing a rapid decline in c-Myc protein levels in NPC cells. Similar to c-Myc knockdown, NPC cells treated with hyperthermia showed growth inhibition associated with the downregulation of c-Myc target genes. Moreover, low levels of c-Myc could be sustainably repressed in NPC cells through repeated hyperthermia treatments. Importantly, the key findings of growth inhibition and decreased c-Myc protein levels were reproduced in NPC tumor xenografts. Bioinformatic analyses showed that downregulation of c-Myc constituted a central node in the hyperthermia response of NPC cells. CONCLUSION: Our study reveals that hyperthermia can readily destabilize c-Myc levels in NPC cells and inhibit tumor growth. This proposes new strategies for implementing hyperthermia to target c-Myc-driven cancers to improve therapeutic efficacy.
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Hipertermia Induzida , Neoplasias Nasofaríngeas , Animais , Linhagem Celular Tumoral , Proliferação de Células/genética , Humanos , Camundongos , Camundongos Nus , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/terapiaRESUMO
Severe acute respiratory syndrome coronavirus (SARS-CoV) was discovered as a novel pathogen in the 2002-2003 SARS epidemic. The emergence and disappearance of this pathogen have brought questions regarding its source and evolution. Within the genome sequences of 281 SARS-CoVs, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and SARS-related CoVs (SARSr-CoVs), a ~430 bp genomic region (from 27 701 bp to 28 131 bp in AY390556.1) with regular variations was investigated. This ~430 bp region overlaps with the ORF8 gene and is prone to deletions and nucleotide substitutions. Its complexity suggested the need for a new genotyping method for coronaviruses related to SARS-similar coronaviruses (SARS-CoV, SARSr-CoV, and SARS-CoV-2). Bat SARSr-CoV presented 3 genotypes, of which type 0 is only seen in bat SARSr-CoV, type I is present in SARS in the early phase, and type II is found in all SARS-CoV-2. This genotyping also shows potential usage in distinguishing the SARS-similar coronaviruses from different hosts and geographic areas. This genomic region has important implications for predicting the epidemic trend and studying the evolution of coronavirus.
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Betacoronavirus/genética , Genoma Viral , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave/genética , Proteínas da Matriz Viral/genética , Animais , Sequência de Bases , Quirópteros/virologia , Eutérios/virologia , Evolução Molecular , Genes Virais , Variação Genética , Humanos , Fases de Leitura Aberta , Filogenia , SARS-CoV-2 , Alinhamento de Sequência , Deleção de Sequência , Glicoproteína da Espícula de Coronavírus/genética , Viverridae/virologiaRESUMO
Nasopharyngeal carcinoma (NPC) is a malignant epithelial cancer of the head and neck with high prevalence in southern China, which is accompanied by notable invasiveness and metastasis. Long noncoding RNAs (lncRNAs) participate in the progression of various cancers including NPC. Microarray-based analysis identified highly expressed lncRNA mothers against decapentaplegic homolog 5 (SMAD5)-antisense RNA 1 (AS1) related to NPC. Interestingly, it is found that SMAD5-AS1 competitively bound to microRNA (miR)-106a-5p to regulate SMAD5. Herein, the study aimed to clarify the role of SMAD5-AS1/miR-106a-5p/SMAD5 axis in the process of epithelial mesenchymal transition (EMT) in NPC. SMAD5-AS1 was highly expressed and miR-106a-5p was poorly expressed in NPC tissues and cell lines. The NPC cells were treated with a series of small interfering RNAs, mimics, or inhibitors to explore the effects of SMAD5-AS1, SMAD5, and miR-106a-5p on EMT, cell proliferation, migration, and invasion in NPC. Of note, SMAD5-AS1 silencing or miR-106a-5p overexpression reduced expression of N-cadherin, matrix metallopeptidase 9, Snail, and Vimentin while elevating E-cadherin expression, thus inhibiting EMT, cell proliferation, migration, and invasion in NPC by down-regulation of SMAD5. Moreover, SMAD5 silencing could reduce the ability of EMT induced by SMAD5-AS1 up-regulation. SMAD5-AS1 silencing or miR-106a-5p elevation inhibited tumorigenesis in nude mice. Taken together, SMAD5-AS1 silencing suppressed EMT, cell proliferation, migration, and invasion in NPC by elevating miR-106a-5p to down-regulate SMAD5, which provided a novel therapeutic target for NPC treatment.-Zheng, Y.-J., Zhao, J.-Y., Liang, T.-S., Wang, P., Wang, J., Yang, D.-K., Liu, Z.-S. Long noncoding RNA SMAD5-AS1 acts as a microRNA-106a-5p sponge to promote epithelial mesenchymal transition in nasopharyngeal carcinoma.
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Transição Epitelial-Mesenquimal/fisiologia , MicroRNAs/genética , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/patologia , Fatores de Transcrição/genética , Carcinogênese/genética , Linhagem Celular Tumoral , Inativação Gênica , Humanos , Carcinoma Nasofaríngeo/genética , Neoplasias Nasofaríngeas/genética , RNA Longo não CodificanteRESUMO
The giant panda (Ailuropoda melanoleuca) is one of the most endangered animals in the world, and it is recognized worldwide as a symbol for conservation. A previous study showed that wild and captive pandas, especially those of the Qinling subspecies, were exposed to toxicants in their diet of bamboo; the ultimate origin of these toxicants is unknown. Here we show that atmospheric deposition is the most likely origin of heavy metals and persistent organic pollutants (POPs) in the diets of captive and wild Qinling pandas. Average atmospheric deposition was 199, 115, and 49 g·m-2 ·yr-1 in the center of Xi'an City, at China's Shaanxi Wild Animal Research Center (SWARC), and at Foping National Nature Reserve (FNNR), respectively. Atmospheric deposition of heavy metals (As, Cd, Cr, Pb, Hg, Co, Cu, Zn, Mn, and Ni) and POPs was highest at Xi'an City, intermediate at SWARC, and lowest at FNNR. Soil concentrations of the aforementioned heavy metals other than As and Zn also were significantly higher at SWARC than at FNNR. Efforts to conserve Qinling pandas may be compromised by air pollution attendant to China's economic development. Improvement of air quality and reductions of toxic emissions are urgently required to protect China's iconic species.
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Monitoramento Ambiental , Poluentes Ambientais/análise , Metais Pesados/análise , Ursidae/metabolismo , Animais , DietaRESUMO
Activation of AMP-activated protein kinase (AMPK) suppressed mammalian target of rapamycin (mTOR) pathway, resulting in impaired cancer cell proliferation. Two cohorts (50 and 1072 cases) of patients with resected gastric adenocarcinoma were enrolled in the study. Immunohistochemical staining for p-AMPKa, p-ACC, p-mTOR, p-S6, and p-4EBP1 was performed on the 50-patient cohort. Tissue microarray blocks containing samples from 1072 patients of Chinese ethnicity were used for the immunohistochemical detection of p-AMPKa and p-S6 levels. p-AMPK and p-ACC were frequently inactivated in both cohorts of gastric cancer samples, while p-mTOR, p-S6, and p-4EBP1 were frequently activated in the small cohort of gastric cancer. However, only levels of p-AMPKa and p-S6 were associated with the overall survival of gastric cancer patients. In the larger 1072-patient cohort, downregulation of p-AMPKa and upregulation of p-S6 were associated with tumor progression and were independent predictors of survival after resection of primary gastric cancer. Therefore, reciprocal expression of p-AMPKa and p-S6 may be promising prognostic biomarkers in patients with gastric cancer.
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Proteínas Quinases Ativadas por AMP/biossíntese , Biomarcadores Tumorais/biossíntese , Proteínas Quinases S6 Ribossômicas 70-kDa/biossíntese , Neoplasias Gástricas/genética , Proteínas Quinases Ativadas por AMP/genética , Acetil-CoA Carboxilase/biossíntese , Acetil-CoA Carboxilase/genética , Proteínas Adaptadoras de Transdução de Sinal/biossíntese , Proteínas Adaptadoras de Transdução de Sinal/genética , Adulto , Idoso , Biomarcadores Tumorais/genética , Proteínas de Ciclo Celular , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Pessoa de Meia-Idade , Proteínas de Neoplasias/biossíntese , Fosfoproteínas/biossíntese , Fosfoproteínas/genética , Fosforilação , Prognóstico , Proteínas Quinases S6 Ribossômicas 70-kDa/genética , Transdução de Sinais , Neoplasias Gástricas/patologia , Serina-Treonina Quinases TOR/biossínteseAssuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimiorradioterapia/mortalidade , Linfoma Extranodal de Células T-NK/terapia , Neoplasias Nasais/terapia , Adolescente , Adulto , Idoso , Asparaginase/administração & dosagem , Criança , Cisplatino/administração & dosagem , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Dexametasona/administração & dosagem , Feminino , Seguimentos , Humanos , Linfoma Extranodal de Células T-NK/patologia , Masculino , Pessoa de Meia-Idade , Neoplasias Nasais/patologia , Polietilenoglicóis/administração & dosagem , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Adulto Jovem , GencitabinaRESUMO
Objective: To investigate the correlation between programmed death ligand 1(PD-L1), tumor mutation burden (TMB) and the short-term efficacy and clinical characteristics of anti-PD-1 immune checkpoint inhibitor combination chemotherapy in NSCLC patients. The efficacy of the prediction model was evaluated. Methods: A total of 220 NSCLC patients receiving first-line treatment with anti-PD-1 immune checkpoint inhibitor combined with chemotherapy were retrospectively collected. The primary endpoint was short-term efficacy ORR. The correlation between short-term efficacy, PD-L1, TMB, and clinical characteristics using χ2 test or t-test was evaluated. Screen the independent prognostic factors using univariate and multivariate logistic regression analyses, and construct a nomogram prediction model using the "rms" package in R software. Using receiver operating characteristic (ROC) curve analysis to evaluate the independent Prognostic factors and the prediction model. Using decision curve analysis (DCA) to verify the superiority of the prediction model. Results: The mean values of PD-L1, TMB, neutrophils, lymphocytes, neutrophil-to-lymphocyte ratio, and albumin were the highest in the ORR group, PD-L1 expression and TMB correlated with epidermal growth factor receptor expression. Multivariate analyses showed that PD-L1, TMB, and neutrophil were independent prognostic factors for ORR. The area under the ROC curve (AUC) values of the ROC constructed based on these three indicators were 0.7104, 0.7139, and 0.7131, respectively. The AUC value under the ROC of the nomogram model was 0.813. The DCA of the model showed that all three indicators used together to build the prediction model of the net return were higher than those of the single indicator prediction model. Conclusion: PD-L1, TMB, and neutrophils are independent prognostic factors for short-term efficacy. The nomogram prediction model constructed using these three indicators can further improve predictive efficacy of ICIs in patients with NSCLC.
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OBJECTIVE: To analyze the efficacy and adverse effects of anti-PD-1 immune checkpoint inhibitors aimed at nasopharyngeal carcinoma (NPC). METHODS: During the first stage of the study, using 40 patients with stage III/IVa NPC treated with anti-PD-1 immune checkpoint inhibitors in combination with chemoradiotherapy as a first-line treatment (observation group) and 70 patients with NPC treated with chemoradiotherapy alone (control group). In the second stage of the study, 88 patients with NPC treated with immune checkpoint inhibitors were grouped according to the number of lines of immunotherapy, the number of times, and the types of application. RESULTS: Observation of the short-term effects in the first stage indicated that the objective response rate (ORR) of the observation group and the control group against primary foci of NPC was 75.0% versus 40.0%; the mortality rate of the observation group was much lower than that of the control group. The overall first-line treatment evaluation of the observation vs. control groups were as follows: ORR (67.5% vs. 38.6%); median PFS (17.52 vs. 17.21 months); and median OS (18.68 vs. 18.14 months), respectively (p < 0.05). The second stage of the study had an ORR of 53.4%, and the efficacy of immunotherapy was related to staging, timing, and frequency. CONCLUSION: Anti-PD-1 immune checkpoint inhibitors combined with chemoradiotherapy as the first-line treatment for nasopharyngeal carcinoma may improve patient outcomes significantly. Timing, frequency, and the type of immunotherapy exerted an effect on the efficacy of immunotherapy. Adverse effects that occurred during treatment were tolerable and controllable.
Assuntos
Quimiorradioterapia , Inibidores de Checkpoint Imunológico , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Receptor de Morte Celular Programada 1 , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/efeitos adversos , Masculino , Feminino , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/terapia , Neoplasias Nasofaríngeas/patologia , Neoplasias Nasofaríngeas/mortalidade , Adulto , Idoso , Quimiorradioterapia/efeitos adversos , Quimiorradioterapia/métodos , Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/mortalidade , Carcinoma Nasofaríngeo/terapia , Carcinoma Nasofaríngeo/patologia , Carcinoma Nasofaríngeo/imunologia , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Estadiamento de Neoplasias , Resultado do Tratamento , Adulto JovemRESUMO
PURPOSE: This phase 3 trial aimed to compare the efficacy and safety of capecitabine or capecitabine plus oxaliplatin (XELOX) with those of fluorouracil plus cisplatin (PF) in definitive concurrent chemoradiotherapy (DCRT) for inoperable locally advanced esophageal squamous cell carcinoma (ESCC). METHODS: Patients were randomly assigned to receive two cycles of capecitabine, XELOX, or PF along with concurrent intensity-modulated radiation therapy. Patients in each arm were again randomly assigned to receive two cycles of consolidation chemotherapy or not. The primary end points were 2-year overall survival (OS) rate and incidence of grade ≥3 adverse events (AEs). RESULTS: A total of 246 patients were randomly assigned into the capecitabine (n = 80), XELOX (n = 85), and PF (n = 81) arms. In capecitabine, XELOX, and PF arms, the 2-year OS rate was 75%, 66.7%, and 70.9% (capecitabine v PF: hazard ratio [HR], 0.91 [95% CI, 0.61 to 1.35]; nominal P = .637; XELOX v PF: 0.86 [95% CI, 0.58 to 1.27]; P = .444); the median OS was 40.9 (95% CI, 34.4 to 49.9), 41.9 (95% CI, 28.6 to 52.1), and 35.4 (95% CI, 30.4 to 45.4) months. The incidence of grade ≥3 AEs during the entire treatment was 28.8%, 36.5%, and 45.7%, respectively. Comparing the consolidation chemotherapy with the nonconsolidation chemotherapy groups, the median OS was 41.9 (95% CI, 34.6 to 52.8) versus 36.9 (95% CI, 28.5 to 44) months (HR, 0.71 [95% CI, 0.52 to 0.99]; nominal P = .0403). CONCLUSION: Capecitabine or XELOX did not significantly improve the 2-year OS rate over PF in DCRT for inoperable locally advanced ESCC. Capecitabine showed a lower incidence of grade ≥3 AEs than PF did.
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Protocolos de Quimioterapia Combinada Antineoplásica , Capecitabina , Quimiorradioterapia , Cisplatino , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Fluoruracila , Oxaliplatina , Humanos , Capecitabina/administração & dosagem , Capecitabina/efeitos adversos , Capecitabina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Feminino , Fluoruracila/análogos & derivados , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Fluoruracila/uso terapêutico , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Cisplatino/uso terapêutico , Neoplasias Esofágicas/terapia , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/mortalidade , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Idoso , Quimiorradioterapia/efeitos adversos , Carcinoma de Células Escamosas do Esôfago/terapia , Carcinoma de Células Escamosas do Esôfago/mortalidade , Carcinoma de Células Escamosas do Esôfago/patologia , Oxaliplatina/administração & dosagem , Oxaliplatina/uso terapêutico , Oxaliplatina/efeitos adversos , Adulto , OxaloacetatosRESUMO
In this paper we update the knowledge on the species of Serica McLeay, 1819 (sensu lato) occurring in Yunnan, Sichuan, and Shaanxi provinces, China. Three new species are described: Sericaallonanhua Liu, Ahrens, Li & Su, sp. nov., S.breviantennalis Liu, Ahrens, Li & Su, sp. nov., and S.fengensis Liu, Ahrens, Li & Su, sp. nov. The key to the species groups and species is updated. The habitus and male genitalia of the new species are illustrated, and a map showing their distribution is provided. New distributional data are given for four species.
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Recently, the dysregulation of circRNAs has been increasingly implicated in the pathogenesis of nasopharyngeal carcinoma (NPC). Among these circRNAs, circMAN1A2 has been highlighted for the up-regulated expression in NPC, whereas the underlying mechanisms have not been clearly established. Thus, the aim of this study was to delineate the tumor-supporting role of circMAN1A2 in the oncogenesis and metastases of NPC. We validated through qRT-PCR that circMAN1A2 was highly expressed in NPC tissues and NPC cells. Survival analysis through Kaplan-Meier method showed that the overall survival, disease-free survival, and distant metastasis-free survival of patients was negatively correlated with the expression of circMAN1A2. Then, gain- and loss-of function assays demonstrated that circMAN1A2 knockdown could impede the proliferation, migration, invasion, and EMT in NPC cells. Further, we conducted dual luciferase reporter gene, RIP, and RNA pull down assays, unveiling that circMAN1A2 functioned as a sponge of miR-135a-3p, and miR-135a-3p targeted UBR5. Additionally, UBR5 interacted with ATMIN to foster the ubiquitination of ATMIN, thereby expediting the malignant behaviors of NPC cells as well as the lung and inguinal lymph node metastases of NPC tumors in vivo. Together, our study uncovered the tumor-initiating and pro-metastatic role of circMAN1A2-miR-135a-3p-UBR5-ATMIN axis in NPC regulation that may be a potential therapeutic target for human NPC.
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MicroRNAs , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , RNA Circular , Ubiquitina-Proteína Ligases , Humanos , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Carcinoma Nasofaríngeo/genética , Neoplasias Nasofaríngeas/genética , RNA Circular/metabolismo , Fatores de Transcrição/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , UbiquitinaçãoRESUMO
Adamantinomatous craniopharyngioma (ACP) is a neuroendocrine tumor whose pathogenesis remains unclear. This study investigated the role of glioma-associated oncogene family zinc finger 1 (GLI1), a transcription factor in the sonic hedgehog (SHH) signaling pathway, in ACP. We discovered that GLI1 regulates the expression of IL-6, thereby triggering inflammatory responses in ACP and influencing the tumor's progression. Analyzing the Gene Expression Omnibus (GEO) database chip GSE68015, we found that GLI1 is overexpressed in ACP, correlating positively with the spite of ACP and inflammation markers. Knockdown of GLI1 significantly inhibited the levels of tumor necrosis factor α, interleukin-6 (IL-6), and IL-1ß in ACP cells, as well as cell proliferation and migration. We further identified a binding site between GLI1 and the promoter region of IL-6, demonstrating that GLI1 can enhance the expression of IL-6. These findings were verified in vivo, where activation of the SHH pathway significantly promoted GLI1 and IL-6 expressions in nude mice, inducing inflammation and tumor growth. Conversely, GLI1 knockdown markedly suppressed these processes. Our study uncovers a potential molecular mechanism for the occurrence of inflammatory responses and tumor progression in ACP.
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Craniofaringioma , Neoplasias Hipofisárias , Animais , Camundongos , Proteínas Hedgehog , Fatores de Transcrição , Interleucina-6 , Craniofaringioma/genética , Camundongos Nus , Proteína GLI1 em Dedos de Zinco/genética , Inflamação , Neoplasias Hipofisárias/genéticaRESUMO
OBJECTIVE: To explore the influence of lymphocyte-to-monocyte ratio (LMR) and neutrophil-to-lymphocyte ratio (NLR) on the prognosis of patients with extranodal NK/T cell lymphoma (ENKTL). METHODS: The clinical data of 203 patients with ENKTL admitted to the First Affiliated Hospital of Zhengzhou University from January 2011 to January 2020 were retrospectively analyzed. The ROC curve determined the limit values of LMR and NLR; Categorical variables were compared using a chi-square test, expressed as frequency and percentage (n,%). Continuous variables were expressed as medians and extremes and compared with the Mann-Whitney U test; Progression-free survival (PFS) and overall survival (OS) of different grouped LMR and NLR patients were analyzed using Kaplan-Meier curves and compared with log-rank tests. The COX proportional risk regression model was used to perform one-factor and multi-factor analysis of PFS and OS. RESULTS: The optimal critical values of LMR and NLR were determined by the ROC curve, which were 2.60 and 3.40, respectively. LMR≤2.60 was more likely to occur in patients with bone marrow invasion (P=0.029) and higher LDH (P=0.036), while NLR≥3.40 was more likely to occur in patients with higher ECOG scores (P=0.002), higher LDH (P=0.008), higher blood glucose (P=0.024), and lower PLT (P=0.010). Kaplan-Meier survival analysis showed that PFS and OS of patients in the high LMR group were significantly better than the low LMR group, while PFS and OS in the low NLR group were significantly better than the high NLR group. The results of multivariate COX analysis showed that EBV-DNA positive (P=0.047), LMR≤2.60 (P=0.014), NLR≥3.40 (P=0.023) were independent risk factors affecting PFS in patients with ENKTL. LMR≤2.60 (P<0.001), NLR≥3.40 (P=0.048), and high ß2-MG (P=0.013) were independent risk factors affecting OS in patients with ENKTL. CONCLUSION: Low LMR and high NLR before treatment are associated with poor prognosis in patients with ENKTL, which also can be used as an easily testable, inexpensive, and practical prognostic indicator in the clinic.
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Linfoma Extranodal de Células T-NK , Monócitos , Humanos , Monócitos/patologia , Neutrófilos , Linfoma Extranodal de Células T-NK/patologia , Estudos Retrospectivos , Linfócitos , PrognósticoRESUMO
In vivo monitoring of treatment response is of great significance for tumor therapy in clinical trials, but it remains a formidable challenge. Herein, we demonstrate a logic AND gate theranostic nanoagent that responds to the coexistence of endogenous and exogenous stimuli, namely HAuCl4@1-Tetradecanol@Gd-based metal-organic framework@SiO2 nanocomposites (APGS NCs). Upon microwave (MW) irradiation, HAuCl4 in the inner part of APGS NCs reacts with the tumor-associated glutathione (GSH). Subsequently, it transforms into an active luminescent form of Au@1-Tetradecanol@Gd-MOF@SiO2 nanocomposites (AuPGS NCs). The intensity of generated fluorescence is correlated with the tumor thermal-injury status. Thus, the generation of AuPGS NCs with high intensity fluorescence under the co-activation of MW and GSH can visualize the treatment effects during MW thermal therapy and instantly modulate the irradiation time and range for optimal outcomes. Hence, this logic gate controlled APGS NCs makes MW thermal therapy eliminate tumor cells completely. This research offers an effective strategy for the design and preparation of activatable theranostic nanoagents for precise tumor imaging and therapy.
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Neoplasias , Medicina de Precisão , Humanos , Micro-Ondas , Dióxido de Silício , Neoplasias/diagnóstico por imagem , Neoplasias/terapia , Neoplasias/patologia , Nanomedicina Teranóstica/métodos , Linhagem Celular TumoralRESUMO
Abnormal long non-coding RNAs (lncRNAs) have been detected in esophageal squamous cell carcinoma (ESCC). Here, we focused on lncRNA ZNF667-AS1 and its downstream mechanism in ESCC progression. Differentially expressed lncRNAs in ESCC were predicted by bioinformatics analysis. ZNF667-AS1, microRNA-1290 (miR-1290), and prune homolog 2 with BCH domain (PRUNE2) expression was determined with their relationship in cell biological processes analyzed also by means of gain- and loss-of-function assays. Xenograft mouse models were performed to re-produce the in vitro findings. We found a decline in ZNF667-AS1 expression in ESCC tissues and cell lines. ZNF667-AS1 overexpression indicated a favorable prognosis of ESCC sufferers. ZNF667-AS1 overexpression suppressed ESCC cell malignant potentials. ZNF667-AS1 reduced miR-1290 to result in upregulation of the miR-1290 target gene PRUNE2. The inhibiting property of ZNF667-AS1 on the malignant characteristics of ESCC cells was achieved by disrupting the miR-1290-mediated downregulation of PRUNE2. ZNF667-AS1 suppressed the tumorigenesis of ESCC in vivo. Collectively, our study demonstrates that ZNF667-AS1 can function as a tumor suppressor in ESCC by upregulating PRUNE2 and downregulating miR-1290.
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INTRODUCTION: Excellent vestibular function (including utricular function) is important for pilots to maintain correct spatial orientation during flight. Vestibular-evoked myogenic potential (VEMP) recorded from extraocular muscles, the so-called ocular VEMP (oVEMP), can be used to evaluate utricular function. However, oVEMP has not been applied to pilots because of lack of reliable normative data. Hence, this study is designed to establish preliminary normative data for oVEMP induced by air-conducted sound in pilots and student pilots. METHODS: There were 62 healthy student pilots (30 male and 32 age-matched female) and 31 healthy male fighter pilots who were recruited as study participants. During binaural air-conducted sound stimulation oVEMP was recorded bilaterally. The latencies of nI and pI, nI-pI interval, peak-to-peak nI-pI amplitude, and asymmetry ratio (AR) of oVEMP in all participants were collected. Meanwhile, the effects of gender and age on oVEMP were also investigated. RESULTS: The latencies of nI and pI, nI-pI interval, nI-pI interpeak amplitude, and AR of oVEMP in all participants were 10.35 +/- 0.66 ms, 15.18 +/- 1.07 ms, 4.75 +/- 0.99 ms, 6.75 +/- 4.13 microV, and 13.22 +/- 9.13%, respectively. No significant difference existed between male student pilots and male pilots in terms of oVEMP parameters. The only significant difference was the nI-pI amplitude between age-matched male and female student pilots: 6.96 +/- 3.85 microV for male student pilots and 5.47 +/- 3.10 microV for female student pilots. CONCLUSIONS: oVEMP should be interpreted with the AR rather than raw amplitude itself. Each institution should determine its own normal values.
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Medicina Aeroespacial , Militares , Potenciais Evocados Miogênicos Vestibulares/fisiologia , Adulto , China , Feminino , Humanos , Masculino , Valores de Referência , Adulto JovemRESUMO
PURPOSE: To analyze the effects of radiotherapy and its timing on the survival and safety of patients with newly diagnosed distant metastatic NPC in non-high-incidence areas. PATIENTS AND METHODS: We retrospectively analyzed 94 newly diagnosed NPC patients with distant metastatic admitted to our hospital from January 2011 to June 2018. They were divided into three groups: no radiotherapy group received chemotherapy alone, early radiotherapy group was combined with radiotherapy during 1 to 3 cycles of chemotherapy, and late radiotherapy group was combined with radiotherapy after 4-6 cycles of chemotherapy were effective. The efficacy and side effects of the three groups were compared, and the prognostic factors were analyzed. RESULTS: The 6-month, 1-year and 2-year PFS were 53.6%, 14.3% and 3.6% in no radiotherapy group, 71.0%, 38.7% and 19.4% in early radiotherapy group, 88.6%, 48.6% and 22.9% in late radiotherapy group; the radiotherapy groups were better than the no radiotherapy group, and the difference was statistically significant (P < 0.017). The 1-year, 2-year and 3-year OS were 75.0%, 32.1% and 0 in no radiotherapy group, 77.4%, 54.8% and 12.9% in early radiotherapy group, 85.7%, 71.4% and 31.4% in late radiotherapy group; the radiotherapy groups were better than the no radiotherapy group, and the differences were statistically significant (P < 0.017). There was no significant difference in OS and PFS between the two radiotherapy groups. Univariate and multivariate analysis showed that HBV (P = 0.031), number of metastases (P = 0.002), liver metastases (P = 0.038), radiotherapy (P < 0.001) and treatment response (P = 0.011) were related to OS. There was no significant difference in the incidence of adverse events (P > 0.017). CONCLUSION: Early and late combined radiotherapy had similar clinical efficacy and both prolonged PFS and OS for patients with newly diagnosed distant metastatic NPC in non-high-risk areas. If chemotherapy response is expected to be poor, radiotherapy can be received early.