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Circular RNAs (circRNAs) possess unique biological properties and distribution characteristics that enable a variety of biological functions. N6-methyladenosine (m6A), a prevalent epigenetic modification in organisms, is regulated by factors including methyltransferases (writers), demethylases (erasers), and m6A-binding proteins (readers). These factors play critical roles in various pathophysiological processes. There is growing evidence that m6A modifications are common within circRNAs, affecting their synthesis, translation, translocation, degradation, and stability. Additionally, circRNAs regulate biological processes that influence m6A modifications. This review explores the metabolism and functions of m6A modifications and circRNAs, their interactions, and their specific regulatory mechanisms in different tumors, offering insights into m6A-circRNA interaction in cancer.
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Adenosina , Neoplasias , RNA Circular , Humanos , RNA Circular/metabolismo , RNA Circular/genética , Neoplasias/genética , Neoplasias/metabolismo , Adenosina/análogos & derivados , Adenosina/metabolismo , AnimaisRESUMO
As a fast and non-destructive spectroscopic analysis technique, Raman spectroscopy has been widely applied in chemistry. However, noise is usually unavoidable in Raman spectra. Hence, denoising is an important step before Raman spectral analysis. A novel spectral denoising method based on variational mode decomposition (VMD) was introduced to solve the above problem. The spectrum is decomposed into a series of modes (uk) by VMD. Then, the high-frequency noise modes are removed and the remaining modes are reconstructed to obtain the denoised spectrum. The proposed method was verified by two artificial noised signals and two Raman spectra of inorganic materials, i.e., MnCo ISAs/CN and Fe-NCNT. For comparison, empirical mode decomposition (EMD), Savitzky-Golay (SG) smoothing, and discrete wavelet transformation (DWT) are also investigated. At the same time, signal-to-noise ratio (SNR) was introduced as evaluation indicators to verify the performance of the proposed method. The results show that compared with EMD, VMD can significantly improve mode mixing and the endpoint effect. Moreover, the Raman spectrum by VMD denoising is more excellent than that of EMD, SG smoothing and DWT in terms of visualization and SNR. For the small sharp peaks, some information is lost after denoising by EMD, SG smoothing, DWT and VMD while VMD loses fewest information. Therefore, VMD may be an alternative method for Raman spectral denoising.
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Radiotherapy is among the routine treatment options for malignant tumors. And it damages DNA and other cellular organelles in target cells by using ionizing radiation produced by various rays, killing the cells. In recent years, multiple studies have demonstrated that exosomes are mechanistically involved in regulating tumor formation, development, invasion and metastasis, and immune evasion. The latest research shows that radiation can affect the abundance and composition of exosomes as well as cell-to-cell communication. In the environment, exosome-carried miRNAs, circRNA, mRNA, and proteins are differentially expressed in cancer cells, while these molecules play a role in numerous biological processes, including the regulation of oncogene expression, mediation of signaling pathways in cancer cells, remodeling of tumor-related fibroblasts, regulation of cell radiosensitivity, and so forth. Therefore, elucidation of the mechanism underlying the role of exosomes in radiotherapy of malignant tumors is crucial for improving the efficacy of radiotherapy. This review will summarize the research advances in radiosensitivity of malignant tumors related to exosomes.
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Exossomos , MicroRNAs , Neoplasias , Comunicação Celular , Exossomos/metabolismo , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias/patologia , Tolerância a RadiaçãoRESUMO
Radiotherapy is an important tool in the treatment of malignant tumors, and exploring how to make radiotherapy more effective is a new way to break through the current bottleneck in the development of radiation oncology. Circular RNAs (circRNAs) are a special class of endogenous non-coding RNAs. Numerous studies have shown that circRNAs have shown great potential in regulating the biological functions of tumors, including proliferation, migration, invasion, and treatment resistance, and that differences in their expression levels are closely related to the clinical prognosis of tumor patients. This review systematically compares the mechanisms of circRNAs in the process of tumor development and radiosensitivity and provides insight into the clinical translation of circRNAs in radiotherapy.
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Neoplasias , RNA Circular , Humanos , Neoplasias/genética , Neoplasias/radioterapia , RNA/genética , RNA/metabolismo , RNA Circular/genética , Tolerância a Radiação/genéticaRESUMO
Porphyrin derivatives are popular photodynamic therapy (PDT) agents; however, their typical insolubility in water has made it challenging to separate cells of organisms in a liquid water environment. Herein, a novel water-soluble 5,10,15,20-tetrakis(4-methoxyphenyl-3-sulfonatophenyl) porphyrin (TMPPS) was synthesized with 95% yield by modifying the traditional sulfonation route. The reaction of TMPPS with AgNO3 afforded AgTMPPS an unusual Ag(II) oxidation state (97% yield). The free base and Ag(II) complex were characterized by matrix-assisted laser desorption ionization-mass spectroscopy, and 1H nuclear magnetic resonance, Fourier-transform infrared, UV-vis, fluorescence, and X-ray photolectron spectroscopies. Upon 460 nm laser irradiation, AgTMPPS generated a large amount of 1O2, whereas no â¦OH was detected. Antibacterial experiments on methicillin-resistant Staphylococcus aureus (MRSA) revealed that the combined action of Agâ ¡ ions and PDT could endow AgTMPPS with a 100% bactericidal ratio for highly concentrated MRSA (108 CFU/mL) at a very low dosage (4 µM) under laser irradiation at 360 J/cm2. Another PDT response was demonstrated by photocatalytically oxidizing 1,4-dihydronicotinamide adenine dinucleotide to NAD+ with AgTMPPS. The structural features of the TMPPS and AgTMPPS molecules were investigated by density functional theory quantum chemical calculations to demonstrate the efficient chemical and photodynamical effects of AgTMPPS for non-invasive antibacterial therapy.
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Staphylococcus aureus Resistente à Meticilina , Porfirinas , Antibacterianos/química , Antibacterianos/farmacologia , NAD/farmacologia , Porfirinas/química , Porfirinas/farmacologia , Prata/química , Prata/farmacologia , Água/farmacologiaRESUMO
Orthogonal frequency division multiplexing non-orthogonal multiple access (OFDM-NOMA) is a promising multi-user access scheme in indoor visible light communication (VLC) systems. In this paper, we propose three novel joint subcarrier and power allocation algorithms in OFDM-NOMA-VLC to improve the throughputs and/or user fairness. These three proposed algorithms address the requirements in fairness-throughput-balanced (FTB), fairness-first (FF), and throughput-first (TF) scenarios, respectively. All of them improve the objective function in the previous joint allocation algorithm and ensure the fairness of users in terms of their overall throughput, rather than that in every subcarrier that is tight and redundant. The designs using the proposed algorithms also exhibit reduced peak-to-average power ratios (PAPRs) and so the average signal power can be better used to further enhance the throughput when the system is limited by the signal peak power. Simulations verify that the proposed algorithms are superior to the previous joint subcarrier and power allocation algorithm as well as the conventional fixed power allocation (FPA) and gain ratio power allocation (GRPA) algorithms. The performance improvement of the proposed algorithms is particularly greater for a larger number of multiplexed users per subcarrier or a larger number of OFDM subcarriers, under which the PAPRs of designs using conventional algorithms are higher. When the total user number, the number of the multiplexed users per subcarrier, and the number of subcarriers are 5, 2, and 16, respectively, the throughputs of the three proposed algorithms are 62.17%, 53.35%, and 67.25% higher than the conventional joint allocation algorithm, while the user fairness is improved by 4.64%, 7.87%, and degraded by 20.71%, respectively. Therefore, the three proposed algorithms can address the requirements in FTB, FF, and TF scenarios, respectively.
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BACKGROUND: CircRNAs play crucial roles in multiple tumours. However, the functions of most circRNAs in cervical cancer remain unclear. METHODS: This study collected GSE113696 data from the GEO database to search for differentially expressed circRNAs in cervical cancer. Quantitative reverse transcription PCR was used to detect the expression level of circNEIL3 in cervical cancer cells and tissues. Then, functional experiments in vitro and in vivo were performed to evaluate the effects of circNEIL3 in cervical cancer. RESULTS: CircNEIL3 was highly expressed in cervical cancer. In vivo and in vitro experiments verified that circNEIL3 enhanced the proliferation capacity of cervical cancer cells. RNA immunoprecipitation, luciferase reporter assay, pull-down assay, and fluorescent in situ hybridization confirmed the interaction between circNEIL3 and miR-137 in cervical cancer. A luciferase reporter assay showed that circNEIL3 adsorbed miR-137 and upregulated KLF12 to regulate the proliferation of cervical cancer cells. CONCLUSIONS: CircNEIL3 is an oncogene in cervical cancer and might serve as a ceRNA that competitively binds to miR-137, thereby indirectly upregulating the expression of KLF12 and promoting the proliferation of cervical cancer cells.
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Radiotherapy is one of the most important treatment methods of tumors. However, the application of radiotherapy in hepatocellular carcinoma (HCC) is limited due to the low tolerance of normal liver cells for radiation and inherent radiation resistance in HCC. With the in-depth study of microRNAs (miRNAs) in tumor therapy, the regulation of tumor radiosensitivity by miRNAs has been a research hotspot in recent years. In the present study, the expression of miR-621 was lower in HCC tissues and cells, and such low expression of miR-621 was associated with poor prognosis in HCC patients. In addition, in vivo and in vitro assays confirmed that the high expression of miR-621 could significantly enhance the radiosensitivity of HCC. Moreover, the expressions of miR-621 and SETDB1 in HCC tissues were negatively correlated. Dual-luciferase reporter assays indicated that miR-621 could directly target the 3' UTR of SETDB1. In addition, miR-621 enhanced the radiosensitivity of HCC cells via directly inhibiting SETDB1. Besides, the miR-621 and/or SETDB1 axis improved the radiosensitivity of HCC cells via activating the p53-signaling pathway. Taken together, miR-621 and/or SETDB1 might be used as a novel therapeutic target for the treatment of HCC.
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Carcinoma Hepatocelular/metabolismo , Histona-Lisina N-Metiltransferase/metabolismo , Neoplasias Hepáticas/metabolismo , MicroRNAs/metabolismo , Micro-Ondas , Radiossensibilizantes/metabolismo , Animais , Carcinoma Hepatocelular/radioterapia , Linhagem Celular Tumoral , Proliferação de Células/genética , Proliferação de Células/efeitos da radiação , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/genética , Células Hep G2 , Histona-Lisina N-Metiltransferase/genética , Humanos , Neoplasias Hepáticas/radioterapia , Camundongos , Camundongos Nus , MicroRNAs/genética , Transdução de Sinais/genética , Transdução de Sinais/efeitos da radiaçãoRESUMO
We propose probabilistically shaped quadrature amplitude modulation (PS-QAM) formats to maximize the capacity in fiber transmission systems using orthogonal chirp-division multiplexing (OCDM). OCDM possesses the property of chirp spread spectrum (CSS), leading to improved resilience to system impairments. We further investigate the recently proposed robust channel estimator based on pulse compression and noise rejection and experimentally demonstrate its feasibility in an intensity-modulated/direction-detection (IM/DD) OCDM system. By applying the proposed PS-QAM based OCDM to an IM/DD optical system, a net information rate of 111.1 Gb/s has been successfully achieved using a 10-GHz class Mach-Zehnder modulator (MZM) and has also shown improved performance compared to the conventional PS-QAM based orthogonal frequency-division multiplexing (OFDM) systems. Moreover, due to the superior characteristics of OCDM, there is no need for additional feedback to obtain the prior knowledge of channel state information in the proposed system, leading to reduced complexity and cost.
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We demonstrated a diversity-reception lens-free underwater wireless optical communication system employing a 2×2 solar panel array as detectors. The respective relationships between solar panel sizes and photocurrents, output voltages, system bandwidths were studied theoretically and experimentally. The signals output from the array were combined via maximum ratio combining in order to improve the signal quality. A 450-nm blue laser was used in the transmitter and a light spot with a size of 20mm×35mm was formed on the receiving plane after a 7-m transmission in tap water. With the solar panel array, a data rate of 84 Mbps was achieved with a bit error rate of 2.17 × 10-3 using 16-QAM OFDM signal. Meanwhile, a single solar panel with the same size as the array only achieved 60 Mbps. Solar panel array can bring about 40% data rate improvement. With the same detection area, the horizontal detection range of detectors increased from 37 mm for single solar panel to 55 mm for solar panel array thanks to the diversity reception. The results show that solar panel array using maximum ratio combining can enhance the transmission data rate as well as the detection range. The impacts of air bubbles, water fluctuation and microscopic particulates suspension on the proposed solar panel array-based system were also investigated. The results show that the received power sensitivity of solar panel array is 5.22 dB higher than single solar panel with the same detection area with a data rate of 60 Mbps and a BER of 10-3.
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BACKGROUND/AIMS: Several studies have verified the correlation between tumor-infiltrating lymphocytes (TILs) and survival of patients with esophagus cancer (EC). However, the prognostic role of TILs is still controversial. Therefore, we performed this meta-analysis. METHODS: We searched PubMed, Embase and the Cochrane Library (last update by August 30, 2017) to identify studies assessing the effect of TILs on survival of patients with EC. Pooled hazard ratios (HRs) for overall survival (OS), disease-free survival (DFS) and cancer specific survival (CSS) were estimated using fixed-effects models or random-effects models, which depends on the heterogeneity. RESULTS: Data from 22 observational studies including 2909 patients were summarized. Pooled analysis indicated that generalized TILs were favorable prognostic markers for OS in patients with EC (pooled HR = 0.48; 95% CI = 0.38-0.61; P < 0.001). For TIL subsets, CD8+ TILs were associated with improved OS (pooled HR = 0.68; 95% CI = 0.58-0.84; P < 0.001) and DFS (pooled HR = 0.90; 95% CI = 0.85-0.95; P < 0.001); FoxP3+ TILs were associated with patients' DFS (pooled HR = 0.88; 95% CI = 0.81-0.96; P = 0.003). High CD57+ TILs indicated a better OS in patients with EC (pooled HR = 0.50; 95% CI = 0.35-0.72; P < 0.001). In addition, the pooled results showed that other TIL subsets including CD3+, CD4+ and CD45RO+ TILs were not associated with patients' survival (P > 0.05). CONCLUSIONS: For patients with EC, some TIL subsets could serve as prognostic biomarkers. The application of TILs in the immunotherapy of EC needs to be verified through a large amount of clinical research.
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Neoplasias Esofágicas/patologia , Linfócitos do Interstício Tumoral/metabolismo , Linfócitos T CD8-Positivos/citologia , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Bases de Dados Factuais , Intervalo Livre de Doença , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/mortalidade , Humanos , Linfócitos do Interstício Tumoral/citologia , Linfócitos do Interstício Tumoral/imunologia , Razão de Chances , Prognóstico , Modelos de Riscos Proporcionais , Taxa de Sobrevida , Subpopulações de Linfócitos T/citologia , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismoRESUMO
BACKGROUND: B-cell-specific moloney leukemia virus insertion site 1 (Bmi-1) plays important roles in various cancers, but its regulation through microRNAs (miRNAs) and its functions in hepatocellular carcinoma (HCC) remains unclear. METHODS: We evaluated the expression and prognostic significance of Bmi-1 in HCC by using tissue samples and The Cancer Genome Atlas (TCGA) data sets. The relationship between miRNAs and Bmi-1 was verified by bioinformatics prediction and immunofluorescence. Colony formation and apoptosis assays were used to reveal the effect of miR-203 on radiosensitivity. RESULTS: The Bmi-1 mRNA and protein were upregulated in HCC tissues. Cox regression multivariate analyses showed that Bmi-1 overexpression was an independent prognostic parameter for HCC patients. The expression level of Bmi-1 was negatively associated with miR-203 levels in HCC tissues. Dual-luciferase reporter assays showed that miR-203 could target the 3' untranslated region (3'-UTR) of Bmi-1 directly. Overexpression of miR-203 in HepG2 and Smmc-7721 cells increases their sensitivity to ionizing radiation in vitro and in vivo. Moreover, the improved cell radiosensitivity induced by miR-203 could be rescued by restoration of Bmi-1 expression. CONCLUSIONS: Bmi-1 could improve the predictive accuracy for HCC patients' survival. Moreover, miR-203 enhance cell radiosensitivity in vitro and in vivo by targeting Bmi-1 in HCC.
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Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , MicroRNAs/metabolismo , Complexo Repressor Polycomb 1/genética , Tolerância a Radiação/genética , Regiões 3' não Traduzidas/genética , Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/terapia , Linhagem Celular Tumoral , Feminino , Regulação Neoplásica da Expressão Gênica , Hepatectomia , Humanos , Fígado/efeitos da radiação , Fígado/cirurgia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/terapia , Masculino , Pessoa de Meia-Idade , Complexo Repressor Polycomb 1/metabolismo , Prognóstico , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Análise de Sobrevida , Análise Serial de Tecidos , Regulação para CimaRESUMO
BACKGROUND: It has been reported that miR-203 expression was aberrant in various types of cancers, and it could be used as a prognostic biomarker. Therefore, in this study, we aimed to evaluate the prognostic value of miR-203 expression in solid tumors by using meta-analysis and The Cancer Genome Atlas (TCGA) datasets. METHODS: By doing a literature research in PubMed, Embase and the Cochrane Library (last update by December 2016), we were able to identify the studies assessing the prognostic role of miR-203 in various tumors. We then used TCGA datasets to validate the results of meta-analysis. RESULTS: 33 studies from 26 articles were qualified and enrolled in this meta-analysis. Pooled analyses showed that higher expression of miR-203 in tissues couldn't predict poor overall survival (OS) and progression-free survival (PFS) in solid tumors. However, the results of subgroup analyses revealed that the upregulation of tissue miR-203 expression was associated with poor OS in colorectal cancer (hazard ratio (HR)=1.81, 95% confidence intervals (CI) 1.31-2.49; P<0.001), pancreatic cancer (HR=1.19, 95% CI 1.09-1.31; P<0.001) and ovarian cancer (HR=1.85, 95% CI 1.45-2.37; P<0.001); but it had opposite association in liver cancer (HR=0.52, 95% CI 0.28-0.97; P=0.040) and esophageal cancer (HR=0.41, 95% CI 0.25-0.66; P<0.001). Based on TCGA datasets, we found the same results for pancreatic cancer and esophageal cancer, but not for colorectal cancer and liver cancer. Moreover, patients with high circulating miR-203 in blood had significantly poor OS and PFS in colorectal cancer and breast cancer. CONCLUSION: Our study showed that the prognostic values of tissue miR-203 varied in different tumor types. In addition, the upregulation of circulating miR-203 in blood was associated with poor prognosis in colorectal cancer and breast cancer.
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Genoma Humano , MicroRNAs/biossíntese , Neoplasias/metabolismo , Neoplasias/mortalidade , RNA Neoplásico/biossíntese , Conjuntos de Dados como Assunto , Intervalo Livre de Doença , Humanos , Taxa de SobrevidaRESUMO
BACKGROUND: This study aimed to investigate the Bmi-1 expression and the clinical significance in colon cancer (CC). PATIENTS AND METHODS: Bmi-1 expression in tumor tissue and the corresponding normal tissue was detected using immunohistological staining. The correlations between Bmi-1 expression and clinicopathological characteristics and the overall survival (OS) time were analyzed. RESULTS: The median H-scores of Bmi-1 in CC tissues and the corresponding tissues were 80.0 (0-270) and 5.0 (0-90), with no statistically significant difference (Z=-13.7, P<0.001). Bmi-1 expression in CC tissues was not statistically correlated with any characteristics. The median OS times for CC patients with high or low Bmi-1 expression were 53.7 months and 44.9 months, respectively, with no statistically significant difference (P = 0.123). The survival rates of patients with low Bmi-1 expression were higher than those of patients with high Bmi-1 expression but the differences were not statistically significant. CONCLUSION: Bmi-1 expression in CC tissue is significantly higher than that in corresponding normal tissue. While there may be a trend towards improved survival, this is not statistically significant.
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Neoplasias do Colo/metabolismo , Complexo Repressor Polycomb 1/metabolismo , Idoso , Neoplasias do Colo/patologia , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Análise de Sobrevida , Taxa de SobrevidaRESUMO
BACKGROUND: Recently, many studies have shown that microRNAs (miRNA) exhibit altered expression in various cancers and may serve as prognostic biomarkers. We performed a systematic review and meta-analysis to evaluate the prognostic role of miR-200c expression in different cancers. METHODS: Studies were recruited by searching PubMed, Embase and the Cochrane Library (last search update was May 2014) and assessed by further quality evaluation. RESULTS: A total of 25 studies dealing with various carcinomas were identified for systematic review. Among them, 18 studies were ultimately included in the meta-analysis. Our results indicated that the expression of tissue miR-200c was not associated with OS and PFS in various carcinomas; however, downregulation of tissue miR-200c did predict poor OS of patients with stage I disease (HR=0.41, 95% CI 0.25-0.68, P=0.001). Furthermore, overexpression of blood miR-200c was significantly related to poor OS and PFS (HR=3.07 95% CI 1.58-5.96 P=0.001, HR=2.26 95% CI 1.66-3.08 P<0.001, respectively), especially in patients with advanced disease. CONCLUSION: This systematic review and meta-analysis clarified that low expression of miR-200c in primary tissue was significantly associated with poor survival in cancer patients at early stage, whereas a high level of blood miR-200c predicted poor prognosis in patients with advanced tumors.
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Biomarcadores Tumorais/biossíntese , MicroRNAs/biossíntese , Neoplasias/genética , Prognóstico , Biomarcadores Tumorais/genética , Humanos , MicroRNAs/genética , Estadiamento de Neoplasias , Neoplasias/patologia , Células Neoplásicas Circulantes , Análise de SobrevidaRESUMO
BACKGROUND/AIMS: The role of Tumor-infiltrating lymphocytes (TILs) in the prognosis of patients with lung cancer is still controversial. We performed a meta-analysis to evaluate the prognostic role of TILs in lung cancer. METHODS: Studies were recruited by searching PubMed, Embase and the Cochrane Library and assessed by further quality evaluation. The pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated to investigate the association between TIL subsets and lung cancer patients' outcome. RESULTS: A total of 29 articles including 8,600 patients were enrolled into the meta-analysis. Our results indicated that high level of CD8+ cells infiltration in tumor stroma (TS) or tumor nest (TN) was associated with better OS in lung cancer patients (HR = 0.76, 95% CI 0.62-0.93, P = 0.006; HR = 0.80, 95% CI 0.67-0.96; P = 0.018, respectively). Similar results could be also observed in CD3+ T cells infiltration. High CD4+ T lymphocytes infiltration in TS was explicitly accompanied by better OS (HR = 0.65, 95% CI 0.46-0.91; P = 0.013), rather than in TN. In contrast, high density of FOXP3+ T cells infiltration in TS showed a poor PFS (HR = 2.67, 95% CI, 1.74-4.08, P < 0.001). CONCLUSION: This meta-analysis clarified that high level of CD8+ and CD3+ T cells infiltration in TS or TN, and high CD4+ T lymphocytes infiltration in TS showed better OS in lung cancer patients, whereas high density of FOXP3+ T cells infiltration in TS could be recognized as a negative prognostic factor.
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Neoplasias Pulmonares/patologia , Linfócitos do Interstício Tumoral/citologia , Linfócitos T CD4-Positivos/citologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD8-Positivos/citologia , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Bases de Dados Factuais , Intervalo Livre de Doença , Fatores de Transcrição Forkhead/metabolismo , Humanos , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/mortalidade , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Razão de Chances , PrognósticoRESUMO
The incidence and mortality rate of esophageal cancer (EC) are higher worldwide. Exosomes are nanoscale vesicles derived from various types of cells, exhibiting a stable presence in bodily fluids, and contain a plethora of bioactive components including proteins, DNA, and RNA. Exosomes can mediate cell-to-cell communication and signaling. Numerous studies conducted both domestically and internationally have indicated the significant involvement of exosomes in tumor development and their potential as novel diagnostic and prognostic biomarkers for liquid biopsy. This review seeks to consolidate the role of exosomes and bioactive substances in the progression of EC and elaborate on the opportunities and challenges associated with the clinical application of exosomes in EC.
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OBJECTIVE: Glutathione peroxidase-4 (GPX4) is a member of Ferroptosis and lipid circulation. This study aims to investigate the expression of GPX4 in esophageal squamous cell carcinoma and its impact on radiosensitivity. METHOD: Immunohistochemistry staining was used to detect GPX4 expression in 180 samples of ESCC tissues and adjacent tissues. We analyzed the relationship between GPX4 expression and ESCC clinical parameters. In vitro experiments were conducted using apoptosis assays and colony formation assays to investigate the effect of GPX4 on the radiosensitivity of ESCC cells. In vivo experiments were carried out using a nude mouse xenograft model to evaluate the impact of GPX4 on the radiosensitivity of ESCC. RESULTS: GPX4 expression was lower in adjacent tissues than tumor tissues. The expression of GPX4 was significantly associated with the pathological grade of ESCC. The overall survival time (OS) of ESCC patients with low GPX4 expression was significantly longer than that of patients with high GPX4 expression. GPX4 could be used as independent prognostic factors in patients with ESCC. In vivo experiments, silencing of GPX4 or using GPX4 inhibitors significantly inhibits the viability and colony formation of ESCC cells after radiation exposure while increasing intracellular reactive oxygen species (ROS) levels, and significantly suppresses the tumorigenic ability of ESCC cells in subcutaneous xenografts after radiation exposure. CONCLUSION: GPX4 is highly expressed in ESCC, which has the potential value for prognostic assessment of ESCC. Silencing or inhibiting GPX4 can enhance the radiosensitivity of ESCC.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Camundongos Nus , Fosfolipídeo Hidroperóxido Glutationa Peroxidase , Tolerância a Radiação , Humanos , Carcinoma de Células Escamosas do Esôfago/genética , Carcinoma de Células Escamosas do Esôfago/patologia , Carcinoma de Células Escamosas do Esôfago/metabolismo , Carcinoma de Células Escamosas do Esôfago/radioterapia , Tolerância a Radiação/genética , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/genética , Animais , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/radioterapia , Masculino , Feminino , Camundongos , Pessoa de Meia-Idade , Prognóstico , Apoptose , Linhagem Celular Tumoral , Ensaios Antitumorais Modelo de Xenoenxerto , Regulação Neoplásica da Expressão Gênica , Idoso , Proliferação de Células , Espécies Reativas de Oxigênio/metabolismo , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/genética , Camundongos Endogâmicos BALB CRESUMO
Cognitive dysfunction is the most common form of radiation-induced brain injury. TDP-43 is known to be associated with hippocampal degeneration and cognitive dysfunction, in this study we wanted to know if it also had an effect on radiation-induced hippocampus damage. At first, we found the expression of TDP-43 and p-TDP-43 was increased in the hippocampus of rats with radiation-induced cognitive dysfunction. Single-cell RNA-seq analysis of the rat hippocampus showed that TDP-43 was expressed in all cell types and was significantly upregulated in neuron cells after irradiation. Enrichment analysis of gene ontology (GO) functions and KEGG pathways showed that the differential expression genes in neuron after irradiation may be involved in synaptic plasticity. In vitro, the expression of TDP-43 was also increased in neuron cells after irradiation, while the expression of brain-derived neurotrophic factor (BDNF), TrkB, typical synaptic signature proteins (SYN, GAP43 and PSD95), ß-tubulin and dendritic spines were decreased. In the irradiated neurons, the ß-tubulin, dendritic and spines typical synaptic signature proteins had more severe damage in pcDNA3.1-TDP-43 plasmid transfections group, however, the damages were alleviated in the siRNA-TDP-43 plasmid transfections group. BDNF was highly expressed in the irradiated pcDNA3.1-TDP-43 plasmid transfections group, while its expression was decreased in the siRNA-TDP-43 group. The TrkB expression was significantly reduced in neurons after exposure to ionizing radiation, however, there was no significant correlation with TDP-43 expression. These data indicate that TDP-43 is involved in radiation-induced neuronal synaptic plasticity decline and developmental damage, furthermore, the BDNF/TrkB signaling pathway may not be involved in this process.
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Fator Neurotrófico Derivado do Encéfalo , Tubulina (Proteína) , Animais , Ratos , Fator Neurotrófico Derivado do Encéfalo/genética , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Hipocampo/metabolismo , Plasticidade Neuronal/fisiologia , Neurônios , RNA Interferente PequenoRESUMO
In recent years, the exploration of immune checkpoint inhibitors (ICIs) has resulted in substantial progress and has changed the pattern of cancer treatment. ICIs have revolutionized the treatment landscape of microsatellite instable colorectal cancer while the efficacy is very limited in patients with microsatellite stable colorectal cancer. Therefore, sensitizing MSS CRC to immunotherapy is a major challenge in the field of CRC immunotherapy. Immunotherapy-based combination therapy is an effective strategy. This review of radiotherapy (RT) as a local treatment has dramatically changed in recent years, and it is now widely accepted that RT can deeply reshape the tumor environment by modulating the immune response. Such evidence gives a strong rationale for the synergism of radiotherapy and immunotherapy, introducing the era of 'immunoradiotherapy'. How to give full play to the synergistic effect of radiotherapy and immunotherapy to improve the therapeutic effect of MSS CRC and bring good prognosis is a hot problem to be solved in the field of cancer treatment.This article reviews the development of CRC immunotherapy, the immune resistance mechanism of MSS CRC, and the impact and potential value of immunotherapy combined with radiotherapy on the immune environment of CRC.