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1.
J Cancer Res Clin Oncol ; 150(5): 232, 2024 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-38703186

RESUMO

BACKGROUND AND PURPOSE: To investigate the effect of combining Endostar with concurrent chemoradiotherapy (ECCRT) compared to concurrent chemoradiotherapy (CCRT) on the regression rate of retropharyngeal lymph nodes (RLNs) and the relationship between regression rate of RLNs and prognosis of patients with locally advanced nasopharyngeal carcinoma (LANPC). METHODS: A total of 122 LANPC patients with RLNs metastasis were included. Metastatic RLNs were delineated both before and after treatment slice by slice on the magnetic resonance images cross-section. The regression rate of RLNs, adverse effects (AE) were evaluated. The median regression rate of RLNs was taken as the cut-off value, and the patients were furtherly divided into high regression rate (HRR) group and low regression rate (LRR) group, then survival times were evaluated. RESULTS: The median regression rates of RLNs in the ECCRT and CCRT groups were 81% and 50%, respectively (P < 0.001). There was no statistically significant difference in the incidence of grade 3/4 AEs between the two groups, except for oral mucositis (ECCRT 26.23% vs. CCRT 44.26%, P = 0.037). The 3-year overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS) and locoregional failure-free survival (LRFFS) rates in the HRR and LRR groups were 85.48% and 86.67% (P = 0.983), 80.65% and 68.33% (P = 0.037), 83.87% and 85% (P = 0.704), 93.55% and 81.67% (P = 0.033), respectively. CONCLUSIONS: Patients in the ECCRT group had higher regression rates of RLNs and lower incidence of severe oral mucositis. Furthermore, patients in the HRR group had a better 3-year PFS and LRFFS rate than those in the LRR group.


Assuntos
Quimiorradioterapia , Metástase Linfática , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Proteínas Recombinantes , Humanos , Masculino , Quimiorradioterapia/efeitos adversos , Quimiorradioterapia/métodos , Feminino , Carcinoma Nasofaríngeo/patologia , Carcinoma Nasofaríngeo/terapia , Carcinoma Nasofaríngeo/mortalidade , Pessoa de Meia-Idade , Estudos Retrospectivos , Prognóstico , Adulto , Neoplasias Nasofaríngeas/patologia , Neoplasias Nasofaríngeas/terapia , Neoplasias Nasofaríngeas/mortalidade , Neoplasias Nasofaríngeas/tratamento farmacológico , Linfonodos/patologia , Linfonodos/diagnóstico por imagem , Endostatinas/administração & dosagem , Idoso , Adulto Jovem
2.
World J Gastrointest Oncol ; 16(4): 1453-1464, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38660649

RESUMO

BACKGROUND: Radiotherapy stands as a promising therapeutic modality for colorectal cancer (CRC); yet, the formidable challenge posed by radio-resistance significantly undermines its efficacy in achieving CRC remission. AIM: To elucidate the role played by microRNA-298 (miR-298) in CRC radio-resistance. METHODS: To establish a radio-resistant CRC cell line, HT-29 cells underwent exposure to 5 gray ionizing radiation that was followed by a 7-d recovery period. The quantification of miR-298 levels within CRC cells was conducted through quantitative RT-PCR, and protein expression determination was realized through Western blotting. Cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and proliferation by clonogenic assay. Radio-induced apoptosis was discerned through flow cytometry analysis. RESULTS: We observed a marked upregulation of miR-298 in radio-resistant CRC cells. MiR-298 emerged as a key determinant of cell survival following radiation exposure, as its overexpression led to a notable reduction in radiation-induced apoptosis. Intriguingly, miR-298 expression exhibited a strong correlation with CRC cell viability. Further investigation unveiled human dual-specificity tyrosine(Y)-regulated kinase 1A (DYRK1A) as miR-298's direct target. CONCLUSION: Taken together, our findings underline the role played by miR-298 in bolstering radio-resistance in CRC cells by means of DYRK1A downregulation, thereby positioning miR-298 as a promising candidate for mitigating radio-resistance in CRC.

3.
Mol Biol Rep ; 51(1): 55, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38165476

RESUMO

BACKGROUND: Reverse transcription quantitative polymerase chain reaction (RT-qPCR) can accurately detect relative gene expression levels in biological samples. However, widely used reference genes exhibit unstable expression under certain conditions. METHODS AND RESULTS: Here, we compared the expression stability of eight reference genes (RPLP0, RPS18, RPL13, EEF1A1, ß-actin, GAPDH, HPRT1, and TUBB) commonly used in liproxstatin-1 (Lip-1)-treated K562 cells using RNA-sequencing and RT-qPCR. The expression of EEF1A1, ACTB, GAPDH, HPRT1, and TUBB was considerably lower in cells treated with 20 µM Lip-1 than in the control, and GAPDH also showed significant downregulation in the 10 µM Lip-1 group. Meanwhile, when we used geNorm, NormFinder, and BestKeeper to compare expression stability, we found that GAPDH and HPRT1 were the most unstable reference genes among all those tested. Stability analysis yielded very similar results when geNorm or BestKeeper was used but not when NormFinder was used. Specifically, geNorm and BestKeeper identified RPL13 and RPLP0 as the most stable genes under 20 µM Lip-1 treatment, whereas RPL13, EEF1A1, and TUBB were the most stable under 10 µM Lip-1 treatment. TUBB and EEF1A1 were the most stable genes in both treatment groups according to the results obtained using NormFinder. An assumed most stable gene was incorporated into each software to validate the accuracy. The results suggest that NormFinder is not an appropriate algorithm for this study. CONCLUSIONS: Stable reference genes were recognized using geNorm and BestKeeper but not NormFinder. Overall, RPL13 and RPLP0 were the most stable reference genes under 20 µM Lip-1 treatment, whereas RPL13, EEF1A1, and TUBB were the most stable genes under 10 µM Lip-1 treatment.


Assuntos
Actinas , Leucemia , Humanos , Células K562 , Sequência de Bases , Análise de Sequência de RNA , Hipoxantina Fosforribosiltransferase , Proteínas de Neoplasias , Proteínas Ribossômicas
4.
World J Gastrointest Oncol ; 16(1): 118-132, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38292835

RESUMO

BACKGROUND: The TGF-ß/SMAD3 and VEGFR-1 signaling pathways play important roles in gastric cancer metastasis. SMAD3 phosphorylation is a crucial prognostic marker in gastric cancer. AIM: To determine the prognostic value and relationship of SMAD3 phospho-isoforms and VEGFR-1 in gastric cancer. METHODS: This was a single-center observational study which enrolled 98 gastric cancer patients and 82 adjacent normal gastric tissues from patients aged 32-84 years (median age 65) between July 2006 and April 2007. Patients were followed up until death or the study ended (median follow-up duration of 28.5 mo). The samples were used to generate tissue microarrays (TMAs) for immunohistochemical (IHC) staining. The expressions of TGF-ß1, pSMAD3C(S423/425), pSMAD3L(S204), and VEGFR-1 in gastric cancer (GC) tumor tissue and normal tissue were measured by IHC staining using TMAs obtained from 98 GC patients. Prognosis and survival information of the patients was recorded by Outdo Biotech from May 2007 to July 2015. The relationship between TGF-ß1, pSMAD3C(S423/425), pSMAD3L(S204), and VEGFR-1 protein expression levels was analyzed using Pearson's correlation coefficient. The relationship between protein expression levels and clinicopathological parameters was analyzed using the Chi-squared test. A survival curve was generated using the Kaplan-Meier survival analysis. RESULTS: TGFß-1 and VEGFR-1 expression was significantly upregulated in gastric cancer tissue compared to adjacent non-cancerous tissue. The positive expression of phosphorylated isoforms of Smad3 varied depending on the phosphorylation site [pSMAD3C(S423/425): 51.0% and pSMAD3L(S204): 31.6%]. High expression of pSMAD3L(S204) was significantly correlated with larger tumors (P = 0.038) and later N stages (P = 0.035). Additionally, high expression of VEGFR-1 was closely correlated with tumor size (P = 0.015) and pathological grading (P = 0.013). High expression of both pSMAD3L(S204) and VEGFR-1 was associated with unfavorable outcomes in terms of overall survival (OS). Multivariate analysis indicated that high expression of pSMAD3L(S204) and VEGFR-1 were independent risk factors for prognosis in GC patients. VEGFR-1 protein expression was correlated with TGF-ß1 (r = 0.220, P = 0.029), pSMAD3C(S423/425) (r = 0.302, P = 0.002), and pSMAD3L(S204) (r = 0.201, P = 0.047), respectively. Simultaneous overexpression of pSMAD3L(S204) and VEGFR-1 was associated with poor OS in gastric cancer patients. CONCLUSION: Co-upregulation of pSMAD3L(S204) and VEGFR-1 can serve as a predictive marker for poor gastric cancer prognosis, and pSMAD3L(204) may be involved in enhanced gastric cancer metastasis in a VEGFR-1-dependent manner.

6.
Adv Mater ; 36(4): e2307218, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37972344

RESUMO

Costly data movement in terms of time and energy in traditional von Neumann systems is exacerbated by emerging information technologies related to artificial intelligence. In-memory computing (IMC) architecture aims to address this problem. Although the IMC hardware prototype represented by a memristor is developed rapidly and performs well, the sneak path issue is a critical and unavoidable challenge prevalent in large-scale and high-density crossbar arrays, particularly in three-dimensional (3D) integration. As a perfect solution to the sneak-path issue, a self-rectifying memristor (SRM) is proposed for 3D integration because of its superior integration density. To date, SRMs have performed well in terms of power consumption (aJ level) and scalability (>102  Mbit). Moreover, SRM-configured 3D integration is considered an ideal hardware platform for 3D IMC. This review focuses on the progress in SRMs and their applications in 3D memory, IMC, neuromorphic computing, and hardware security. The advantages, disadvantages, and optimization strategies of SRMs in diverse application scenarios are illustrated. Challenges posed by physical mechanisms, fabrication processes, and peripheral circuits, as well as potential solutions at the device and system levels, are also discussed.

7.
Spectrochim Acta A Mol Biomol Spectrosc ; 309: 123811, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38154303

RESUMO

In this work, a biosensor based on Fano resonance metasurface is proposed for the specific detection of CA242 which is a typical marker of pancreatic cancer. The biosensor consists of a chiral symmetric plasma double "N" structure, which utilises coherent coupling of bright and dark modes to generate Fano resonance, achieving suppression of radiation loss, concentrating and storing energy more efficiently in the structure, and contributing to increased sensitivity to changes in ambient refractive index, resulting in a sensitivity of the sensor of up to 842.8 nm /RIU. After a series of antibody functionalization modifications, the metasurface has become an immune biosensor that can specifically detect the tumor marker CA242 of pancreatic cancer. The detection of mixed and single antigen solutions with different concentrations has verified the high sensitivity, high specificity, and high linear relationship of the biosensor to CA242, and the detection limit is as low as 0.0692 ng/mL. It is superior to other common methods and breaks the traditional disadvantages of lower detection accuracy and greater damage in tumour detection methods. The detection of the wavelength shift of localized surface plasmon resonance in plasma metasurface has been successfully applied to the highly sensitive detection of tumor markers. This study demonstrates the sensitivity and maneuverability of the chiral symmetric double "N" plasmonic metasurface biosensor, suggesting the potential application of metamaterials in biosensing based on environmental refractive index changes.


Assuntos
Técnicas Biossensoriais , Neoplasias Pancreáticas , Humanos , Ressonância de Plasmônio de Superfície/métodos , Anticorpos , Sensibilidade e Especificidade , Biomarcadores Tumorais
8.
Exp Eye Res ; 239: 109759, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38142763

RESUMO

Early diagnosis is important for improving the outcomes of keratoconus (KC). Stable expression and a closed-loop structure of circular RNAs (circRNAs) make them ideal for the diagnosis and treatment of diseases. However, the expression pattern and potential function of circRNAs in KC is not studied yet. Hence, this study explored the circRNA expression profile of KC corneas through transcriptome sequencing and circRNA expression profile analysis. The diagnostic potential of blood circRNAs for KC was explored by analysing the circRNAs' expression levels of fifty paired blood samples from patients with KC and normal controls. The results showed that 107 significantly upregulated and 145 significantly downregulated circRNAs (|fold change| ≥ 2.0, p-value <0.05) were identified in KC tissues. Eight top differently expressed circRNAs were further validated in more cornea samples. Among them, five circRNAs expressed in peripheral blood, and four circRNAs (circ_0006156, circ_0006117, circ_0000284 and circ_0001801) showed significant downregulation in KC patients' peripheral blood too. The blood circ_0000284 expression levels of early, moderate, and advanced KC patients both were significantly lower than the controls. The blood circ_0006117 expression levels present a positive correlation with corrected distance visual acuity values, and a negative correlation with back elevation values of KC eyes. Notably, the expression levels of these circRNAs distinguished KC patients from their healthy counterparts, with the area under the curve (AUC) of circ_0000284, circ_0001801, and circ_0006117 being 0.7306, 0.6871 and 0.6701, respectively. Further, the AUC value for five circRNAs under the logistic regression model was 0.8203, indicating that they can function as effective biomarkers for the KC diagnostics. In conclusion, the expression of circRNAs showed a relationship with KC, with four significantly differentially expressed circRNAs demonstrating potential as biomarkers for the disease.


Assuntos
Ceratocone , RNA Circular , Humanos , RNA Circular/genética , Ceratocone/diagnóstico , Ceratocone/genética , Biomarcadores/metabolismo , Regulação para Baixo , Área Sob a Curva , RNA/genética , RNA/metabolismo
9.
Nat Commun ; 14(1): 5343, 2023 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-37660168

RESUMO

MAVS is an adapter protein involved in RIG-I-like receptor (RLR) signaling in mitochondria, peroxisomes, and mitochondria-associated ER membranes (MAMs). However, the role of MAVS in glucose metabolism and RLR signaling cross-regulation and how these signaling pathways are coordinated among these organelles have not been defined. This study reports that RLR action drives a switch from glycolysis to the pentose phosphate pathway (PPP) and the hexosamine biosynthesis pathway (HBP) through MAVS. We show that peroxisomal MAVS is responsible for glucose flux shift into PPP and type III interferon (IFN) expression, whereas MAMs-located MAVS is responsible for glucose flux shift into HBP and type I IFN expression. Mechanistically, peroxisomal MAVS interacts with G6PD and the MAVS signalosome forms at peroxisomes by recruiting TNF receptor-associated factor 6 (TRAF6) and interferon regulatory factor 1 (IRF1). By contrast, MAMs-located MAVS interact with glutamine-fructose-6-phosphate transaminase, and the MAVS signalosome forms at MAMs by recruiting TRAF6 and TRAF2. Our findings suggest that MAVS mediates the interaction of RLR signaling and glucose metabolism.


Assuntos
Via de Pentose Fosfato , Fator 6 Associado a Receptor de TNF , Proteínas Adaptadoras de Transdução de Sinal , Glucose , Glicólise , Hexosaminas , Humanos , Animais , Camundongos , Transdução de Sinais
10.
Sci Adv ; 9(25): eadf7474, 2023 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-37343101

RESUMO

Memristor-enabled in-memory computing provides an unconventional computing paradigm to surpass the energy efficiency of von Neumann computers. Owing to the limitation of the computing mechanism, while the crossbar structure is desirable for dense computation, the system's energy and area efficiency degrade substantially in performing sparse computation tasks, such as scientific computing. In this work, we report a high-efficiency in-memory sparse computing system based on a self-rectifying memristor array. This system originates from an analog computing mechanism that is motivated by the device's self-rectifying nature, which can achieve an overall performance of ~97 to ~11 TOPS/W for 2- to 8-bit sparse computation when processing practical scientific computing tasks. Compared to previous in-memory computing system, this work provides over 85 times improvement in energy efficiency with an approximately 340 times reduction in hardware overhead. This work can pave the road toward a highly efficient in-memory computing platform for high-performance computing.

11.
Comput Biol Med ; 163: 107119, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37364533

RESUMO

Generative adversarial networks (GANs) and their variants as an effective method for generating visually appealing images have shown great potential in different medical imaging applications during past decades. However, some issues remain insufficiently investigated: many models still suffer from model collapse, vanishing gradients, and convergence failure. Considering the fact that medical images differ from typical RGB images in terms of complexity and dimensionality, we propose an adaptive generative adversarial network, namely MedGAN, to mitigate these issues. Specifically, we first use Wasserstein loss as a convergence metric to measure the convergence degree of the generator and the discriminator. Then, we adaptively train MedGAN based on this metric. Finally, we generate medical images based on MedGAN and use them to build few-shot medical data learning models for disease classification and lesion localization. On demodicosis, blister, molluscum, and parakeratosis datasets, our experimental results verify the advantages of MedGAN in model convergence, training speed, and visual quality of generated samples. We believe this approach can be generalized to other medical applications and contribute to radiologists' efforts for disease diagnosis. The source code can be downloaded at https://github.com/geyao-c/MedGAN.


Assuntos
Educação Médica , Humanos , Aprendizagem , Radiologistas , Software , Processamento de Imagem Assistida por Computador
12.
Front Clin Diabetes Healthc ; 4: 1181729, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37228785

RESUMO

Background: Obesity in pediatric patients is strongly associated with increased vascular and metabolic risk. Prediabetes is present in up to 1 in 5 adolescents, aged 12-18 years-old, though is thought to remit spontaneously in a significant portion. Pediatric patients with type 2 diabetes mellitus (T2D) have a more rapid decline of beta-cell function and progression to treatment failure than adult T2D patients. Thus, there is a strong interest in better understanding the natural history of prediabetes in these youth. We aimed to evaluate the real-world rate of progression of prediabetes to T2D in adolescent patients. Methods: This is a retrospective study of 9,275 adolescent subjects aged 12-21 years-old with at least 3 years of de-identified commercial claims data and a new diagnosis of prediabetes during the observation period. Enrollees with a T2D diagnosis and/or diabetes medication use in the 1 year prior to prediabetes diagnosis or a T2D diagnosis in the 1 month following prediabetes diagnosis were excluded. Enrollees with diagnoses of type 1 diabetes (T1D) or polycystic ovarian syndrome over the 3 years were also excluded. Progression to T2D was defined by claims data of two T2D diagnoses at least 7 days apart, HbA1c ≥ 6.5%, and/or prescription of insulin without known T1D. Enrollees were followed for 2 years after prediabetes diagnosis. Results: Overall, 232 subjects (2.5%) progressed from prediabetes to T2D. There were no differences found in T2D progression based on sex or age. Progression to T2D occurred at a median of 302 days after prediabetes diagnosis (IQR 123 to 518 days). This study was limited by the lack of laboratory/anthropometric data in administrative claims, as well as the exclusion of 23,825 enrollees for lack of continuous commercial claims data over 3 years. Conclusion: In the largest sample to date on adolescent prediabetes, we found a 2.5% progression of prediabetes to T2D over a median duration of about one year.

13.
World J Gastroenterol ; 29(13): 1911-1941, 2023 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-37155531

RESUMO

Colorectal cancer (CRC) is the most common digestive malignancy across the world. Its first-line treatments applied in the routine clinical setting include surgery, chemotherapy, radiotherapy, targeted therapy, and immunotherapy. However, resistance to therapy has been identified as the major clinical challenge that fails the treatment method, leading to recurrence and distant metastasis. An increasing number of studies have been attempting to explore the underlying mechanisms of the resistance of CRC cells to different therapies, which can be summarized into two aspects: (1) The intrinsic characters and adapted alterations of CRC cells before and during treatment that regulate the drug metabolism, drug transport, drug target, and the activation of signaling pathways; and (2) the suppressive features of the tumor microenvironment (TME). To combat the issue of therapeutic resistance, effective strategies are warranted with a focus on the restoration of CRC cells' sensitivity to specific treatments as well as reprogramming impressive TME into stimulatory conditions. To date, nanotechnology seems promising with scope for improvement of drug mobility, treatment efficacy, and reduction of systemic toxicity. The instinctive advantages offered by nanomaterials enable the diversity of loading cargoes to increase drug concentration and targeting specificity, as well as offer a platform for trying the combination of different treatments to eventually prevent tumor recurrence, metastasis, and reversion of therapy resistance. The present review intends to summarize the known mechanisms of CRC resistance to chemotherapy, radiotherapy, immunotherapy, and targeted therapy, as well as the process of metastasis. We have also emphasized the recent application of nanomaterials in combating therapeutic resistance and preventing metastasis either by combining with other treatment approaches or alone. In summary, nanomedicine is an emerging technology with potential for CRC treatment; hence, efforts should be devoted to targeting cancer cells for the restoration of therapeutic sensitivity as well as reprogramming the TME. It is believed that the combined strategy will be beneficial to achieve synergistic outcomes contributing to control and management of CRC in the future.


Assuntos
Neoplasias Colorretais , Resistencia a Medicamentos Antineoplásicos , Humanos , Nanotecnologia , Sistemas de Liberação de Medicamentos , Imunoterapia , Neoplasias Colorretais/tratamento farmacológico , Microambiente Tumoral
14.
J Thorac Oncol ; 18(4): 436-446, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36379356

RESUMO

INTRODUCTION: Most published guidelines for genomic biomarker testing in NSCLC reflect the disease epidemiology and treatments readily available in Europe and North America. Nevertheless, 60% of annual global NSCLC cases occur in Asia, where patient characteristics, tumor molecular profiles, and treatments vary greatly from the Western world. For example, mutations in the EGFR occur at a higher prevalence in Asia than in other world regions. Although medical associations such as the International Association for the Study of Lung Cancer, European Society for Medical Oncology, and American Society of Clinical Oncology have described principles for tumor genomic biomarker testing in NSCLC, there is a need for recommendations specific for Asia. METHODS: This report provides consensus recommendations for NSCLC biomarker testing from Asian lung cancer experts for clinicians working in Asia to improve patient care. Biomarker testing approaches for actionable genetic alterations in EGFR, ALK, ROS1, and others are discussed. RESULTS: These recommendations are divided into nonmetastatic and metastatic forms of adenocarcinoma and squamous cell carcinoma. Owing to the higher prevalence of EGFR mutations in Asia, the experts emphasized the need for EGFR testing to include not just common mutations (exon 19 deletions and L858R substitutions) but also other uncommon EGFR mutations. In addition to the assessment of biomarkers in the tumor tissue, the role of assessing tumor biomarkers by liquid biopsy is discussed. CONCLUSION: This consensus provides practical recommendations for biomarker testing in nonmetastatic and metastatic Asian NSCLC patients.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/patologia , Consenso , Proteínas Tirosina Quinases/genética , Receptores ErbB/genética , Proteínas Proto-Oncogênicas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Mutação , Biomarcadores Tumorais/genética , Ásia/epidemiologia
15.
Transl Oncol ; 27: 101576, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36343416

RESUMO

Radiotherapy is a valid treatment for nasopharyngeal carcinoma (NPC), and radioresistance is the main cause of local NPC treatment failure. However, the underlying mechanisms and valuable markers of radioresistance for NPC remain have not been established. In this study, we observed that the m6A mRNA demethylase fat mass and obesity-associated protein (FTO) was significantly upregulated in radioresistant NPC tissues and cells relative to parental radiosensitive NPC tissues and cells. FTO enhances radioresistance by repressing radiation-induced ferroptosis in NPC. Mechanistically, FTO acts as an m6A demethylase to erase the m6A modification of the OTUB1 transcript and promote the expression of OTUB1, thereby inhibiting the ferroptosis of cells induced by radiation and finally triggering the radiotherapy resistance of NPC. Furthermore, our in vivo experiment results showed that the FTO inhibitor, FB23-2, and the ferroptosis activator, erastin, altered tumor responsiveness to radiotherapy in NPC cell lines and patient-derived xenografts. Our findings reveal, for the first time, that FTO enhances NPC radiotherapy resistance by withstanding radiation-induced ferroptosis, suggesting that FTO may serve as a potential therapeutic target and valuable prognostic biomarker in patients with NPC.

16.
IEEE/ACM Trans Comput Biol Bioinform ; 20(4): 2598-2609, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36201418

RESUMO

Medical images are an important basis for doctors to diagnose diseases, but some medical images have low resolution due to hardware technology and cost constraints. Super-resolution technology can reconstruct low-resolution medical images into high-resolution images and enhance the quality of low-resolution images, thus assisting doctors in diagnosing diseases. However, traditional super-resolution methods mainly learn the mapping relationships among modal pixels from low resolution to high resolution, lacking the learning of high-level semantic features, resulting in a lack of understanding and utilization of semantic information, such as reconstructed objects, object attributes, and spatial relationships between two objects. In this paper, we propose a medical image super-resolution method based on semantic perception transfer learning. First, we propose a novel semantic perception super-resolution method that empowers super-resolution models to perceive high-level semantics by transferring features of the image description generation network in natural language processing. Second, we construct a semantic feature extraction network and an image description generation network and comprehensively utilized image and text modal data to learn transferable, high-level semantic features. Third, we train an end-to-end, semantic perception super-resolution model by fusing dynamic perceptual convolution, a semantic extraction network, and distillation polarization self-attention. Experiments show that semantic perception transfer learning can effectively improve the quality of super-resolution reconstruction.

17.
Acta Pharmaceutica Sinica ; (12): 2375-2383, 2023.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-999113

RESUMO

Krüppel-like transcription factor 2 (KLF2) plays a key regulatory role in endothelial inflammation, thrombosis, angiogenesis and macrophage inflammation and polarization, and up-regulation of KLF2 expression has the potential to prevent and treatment atherosclerosis. In this study, trichostatin C (TSC) was obtained from the secondary metabolites of rice fermentation of Streptomyces sp. CPCC 203909 as a KLF2 up-regulator by using a high throughput screening model based on a KLF2 promoter luciferase reporter assay. TSC significantly inhibited the adhesion of tumor necrosis factor-α (TNFα) induced monocytes (THP-1) to human umbilical vein endothelial cells (HUVECs). Western blot results showed that TSC decreased TNFα induced the protein expression increase of vascular cell adhesion molecule-1 (VCAM-1), and thereby inhibited endothelial inflammation. The results of histone deacetylase (HDAC) overexpression and molecular docking experiments showed that TSC upregulated the expression of KLF2 by inhibiting subtypes of HDAC 4/5/7. In conclusion, this study suggests that TSC up-regulates the expression of KLF2 through inhibiting HDAC 4/5/7 and thus inhibits TNFα induced endothelial inflammation, and it has the potential to prevent and treat atherosclerosis.

18.
Radiother Oncol ; 177: 185-190, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36375560

RESUMO

PURPOSE: Whether cervical lymph node necrosis (CNN) is an independent adverse prognostic factor in nasopharyngeal carcinoma (NPC) has not been determined. In this study, the CNN ratio was graded quantitatively to explore the prognostic value in NPC. PARTICIPANTS AND METHODS: We retrospectively reviewed a total of 648 pathologically confirmed as NPC. We outlined metastatic lymph nodes and necrotic area of lymph nodes slice by slice on the magneticresonanceimages (MRI) cross section, and calculated the corresponding CNN ratio. RESULTS: The median CNN ratio (17.37 %) was taken as the cut-off point, 256 (39.51 %) patients were divided into CNN1 group (<17.37 %, n = 128) and CNN2 group (≥17.37 %, n = 128), 392 (60.49 %) patients without lymph nodes necrosis were CNN0. Among the CNN0, CNN1 and CNN2 groups, five-year overall survival (OS) was 82.4 %, 76.6 % and 71.1 %, locoregional recurrence-free survival (LRRFS) was 91.3 %, 91.1 % and 90.5 %, distant metastasis-free survival (DMFS) was 83.7 %, 78.5 % and 68.7 %, progression-free survival (PFS) was 78.3 %, 71.7 % and 61.6 % respectively. By multivariate analysis, CNN was an independent prognostic factor for OS (P = 0.003), DMFS (P = 0.019) and PFS (P = 0.007). More than 3 cycles of chemotherapy significantly increased OS (P = 0.024) and DMFS (P = 0.015) in the CNN1 group. CONCLUSIONS: This study indicated that CNN is one of the factors with the negative prognosis of NPC. The CNN ratio might be used as one of the reference factors in the formulation of individualized treatment plan.


Assuntos
Carcinoma , Neoplasias Nasofaríngeas , Radioterapia de Intensidade Modulada , Humanos , Carcinoma Nasofaríngeo/patologia , Prognóstico , Neoplasias Nasofaríngeas/patologia , Estudos Retrospectivos , Metástase Linfática/patologia , Estadiamento de Neoplasias , Carcinoma/patologia , Linfonodos/patologia , Necrose/patologia
19.
Genet Res (Camb) ; 2022: 2485055, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36118276

RESUMO

The clinical significance and potential targets of miR-150-5p have not been elucidated in nasopharyngeal carcinoma (NPC). The pooled analysis based on 539 NPC samples and 75 non-NPC nasopharyngeal samples demonstrated that the expression of miR-150-5p was down-regulated in NPC, with the area under the curve being 0.89 and the standardized mean difference being -0.66. Subsequently, we further screened the differentially expressed genes (DEGs) of 14 datasets, including 312 NPC samples and 70 non-NPC nasopharyngeal samples. After the DEGs were narrowed down with the predicted targets from the miRWalk database, 1316 prospective target genes of miR-150-5p were identified. The enrichment analysis suggested that "pathways in cancer" was the most significant pathway. Finally, six hub genes of "pathways in cancer", including EGFR, TP53, HRAS, CCND1, CDH1, and FGF2, were screened out through the STRING database. In conclusion, the down-regulation of miR-150-5p modulates the tumorigenesis and progression of NPC.


Assuntos
MicroRNAs , Carcinoma Nasofaríngeo , Receptores ErbB/genética , Receptores ErbB/metabolismo , Fator 2 de Crescimento de Fibroblastos/genética , Fator 2 de Crescimento de Fibroblastos/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Carcinoma Nasofaríngeo/genética , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/patologia
20.
Infect Drug Resist ; 15: 4585-4593, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35999830

RESUMO

Purpose: To describe the development of bacterial keratitis after small incision lenticule extraction in 5 patients and to explore its appropriate therapies. Methods: We retrospectively summarized the clinical treatments of five patients with postoperative bacterial infection after small incision lenticule extraction, who were referred to our hospital from 2019 to 2021. Results: Five male patients had undergone bilateral SMILE in the local hospital due to myopia aged from 18 to 26 years. The onset of keratitis during 1-3 days postoperatively and four of them were severe infection (2 bilateral, 2 unilateral). In five cases, 1 patient (1 eye) who was infected mild keratitis after SMILE was treated with only topical antibiotics; the others who respond poorly to topical antibiotics require surgical treatment, which 1 patient (1 eye) infected necrotic mass of the corneal cap was scraped and irrigated with antibiotic, and 3 patients (5 eyes) were treated by converting the cap to flap, curetting the necrotic tissue and irrigating with the antibiotic solution. In all patients, the duration from onset to resolution was 1-5 weeks. The final uncorrected visual acuity was above 20/32. Conclusion: Owing to the upward popularity of refractive surgery, the incidence of keratitis after SMILE should not be ignored. Early diagnosis and timely treatment of post-SMILE keratitis are essential. For severe keratitis that fails to respond to topical antibiotics, the corneal cap should be opened as a flap.

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