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1.
Appl Opt ; 63(9): 2187-2194, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38568571

RESUMO

We designed a cascaded all-soft-glass fiber structure and simulate midinfrared 2-20 µm ultrawideband supercontinuum (SC) generation numerically. The cascaded fiber structure consists of a 1.5 m I n F 3 fiber, a 0.2 m chalcogenide photonic crystal fiber, and a 0.2 m tellurium-based chalcogenide photonic crystal fiber. Using a 2 µm pulse pumping this cascaded structure, the generated SC covering the wavelengths longer than 20 µm has been demonstrated theoretically. The 30 dB bandwidth reaches 20.87 µm from 1.44 to 22.31 µm. The effect of different pulse widths on SC generation is considered. With the increase of peak power and the decrease of pulse width, the energy of SC in the 15-20 µm waveband increases gradually. The mechanism of SC broadening process has also been analyzed. The SC generation of more than 20 µm in this cascade structure is caused by the self-phase modulation, soliton effects, four-wave mixing, and redshifted dispersive wave. This method demonstrates the possibility of generating ultrawide bandwidth SCs up to a 20 µm waveband by a commercial 2 µm pump source and all-fiber structure.

2.
Zookeys ; 1193: 145-160, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38487668

RESUMO

The genus Svistella Gorochov, 1987 includes 10 species from Asia, with nine documented in China. In this study, a new species, Svistellayayun He, sp. nov., is described from Xizang, China. Morphologically, it resembles S.rufonotata (Chopard, 1932) but can be distinguished by a smaller inner tympanum, dark-brown setae on the 5th segment of the maxillary palp, and a rounded apex on the ectoparamere. To validate our morphological inferences and support the description of S.yayunsp. nov. as a new species, we performed a PCA based on bioacoustics parameters and molecular analysis. All Svistella species documented in China are distinguished by integrating their songs and DNA barcoding.

3.
Zootaxa ; 5311(1): 48-64, 2023 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-37518656

RESUMO

We report five new Myanmar amber specimens attributable to "Mole Cricket" †Pherodactylus rectanguli n. comb., hitherto regarded as a Mole Cricket (Orthoptera: Grylloptalpidae). The new material includes two adult males, two adult females, and one nymph. The specimens are redescribed, and additional new characters are provided for their delimitation and corresponding species identification. We carry out a comparison between these new specimens with other taxa of mole crickets from Myanmar amber and extant true crickets. The result indicates that some species merely represent different nymphal development stages or adults of †Pherodactylus rectanguli n. comb., however, they were misidentified as different species. We also treated genera †Tresdigitus n. syn. and †Chunxiania n. syn. as synonyms of genus †Pherodactylus Poinar, Su & Brown, 2020, and treat †Tresdigitus gracilis Jiang, Xu, Jarzembowski & Xiao, 2022 n. syn. and †Chunxiania fania n. syn. as synonyms of †Pherodactylus rectanguli n. comb. †Burmagryllotalpa longa is valid, because its shape of the pronotum curved without lateral carinae. The morphological convergences and specializations of subterranean dwelling species are discussed. The robust fore tibia and long apical spurs of †P. micromorphus, †P. rectanguli n. comb. and †B. longa are insufficient evidence for an assignment to the family Gryllotalpidae. Instead, we suggest place them into the subfamily Gryllinae (Gryllidae), tribe Sclerogryllini, and group them into their own subtribe Pherodactylina n. subtr.. A key to the identification of recent and fossil Sclerogryllini is also provided. Their taxonomy and morphology are discussed.


Assuntos
Gryllidae , Ortópteros , Feminino , Masculino , Animais , Âmbar , Fósseis , Mianmar , Ninfa
4.
Biomacromolecules ; 24(4): 1662-1674, 2023 04 10.
Artigo em Inglês | MEDLINE | ID: mdl-36913719

RESUMO

Numerous metabolic reactions and pathways use adenosine 5'-triphosphate (ATP) as an energy source and as a phosphorous or pyrophosphorous donor. Based on three-dimensional (3D)-printing, enzyme immobilization can be used to improve ATP regeneration and operability and reduce cost. However, due to the relatively large mesh size of 3D-bioprinted hydrogels soaked in a reaction solution, the lower-molecular-weight enzymes cannot avoid leaking out of the hydrogels readily. Here, a chimeric adenylate-kinase-spidroin (ADK-RC) is created, with ADK serving as the N-terminal domain. The chimera is capable of self-assembling to form micellar nanoparticles at a higher molecular scale. Although fused to spidroin (RC), ADK-RC remains relatively consistent and exhibits high activity, thermostability, pH stability, and organic solvent tolerance. Considering different surface-to-volume ratios, three shapes of enzyme hydrogels are designed, 3D bioprinted, and measured. In addition, a continuous enzymatic reaction demonstrates that ADK-RC hydrogels have higher specific activity and substrate affinity but a lower reaction rate and catalytic power compared to free enzymes in solution. With ATP regeneration, the ADK and ADK-RC hydrogels significantly increase the production of d-glucose-6-phosphate and obtain an efficient usage frequency. In conclusion, enzymes fused to spidroin might be an efficient strategy for maintaining activity and reducing leakage in 3D-bioprinted hydrogels under mild conditions.


Assuntos
Adenilato Quinase , Fibroínas , Adenilato Quinase/química , Adenilato Quinase/metabolismo , Hidrogéis , Trifosfato de Adenosina/química , Catálise
5.
Nanotechnology ; 34(20)2023 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-36801839

RESUMO

Metal-organic frameworks (MOFs) offer an intrinsically porous and chemically tunable platform for gas adsorption, separation, and catalysis. We investigate thin film derivatives of the well-studied Zr-O based MOF powders to understand their adsorption properties and reactivity with their adaption to thin films, involving diverse functionality with the incorporation of different linker groups and the inclusion of embedded metal nanoparticles: UiO-66, UiO-66-NH2, and Pt@UiO-66-NH2. Using transflectance IR spectroscopy, we determine the active sites in each film upon consideration of the acid-base properties of the adsorption sites and guest species, and perform metal-based catalysis with CO oxidation of a Pt@UiO-66-NH2film. Our study shows how surface science characterization techniques can be used to characterize the reactivity and the chemical and electronic structure of MOFs.

6.
Prep Biochem Biotechnol ; 53(8): 914-922, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36573266

RESUMO

Due to their advantages in structural stability and versatility, cysteine-rich peptides, which are secreted from the venom glands of venomous animals, constitute a naturally occurring pharmaceutical arsenal. However, the correct folding of disulfide bonds is a challenging task in the prokaryotic expression system like Escherichia coli due to the reducing environment. Here, a secretory expression plasmid pSE-G1M5-SUMO-HWTX-I for the spider neurotoxin huwentoxin-I (HWTX-I) with three disulfides as a model of cysteine-rich peptides was constructed. By utilizing the signal peptide G1M5, the fusion protein 6 × His-SUMO-HWTX-I was successfully secreted into extracellular medium of BL21(DE3). After enrichment using cation-exchange chromatography and purification utilizing the Ni-NTA column, 6 × His-SUMO-HWTX-I was digested via Ulp1 kinase to release recombinant HWTX-I (rHWTX-I), which was further purified utilizing RP-HPLC. Finally, both impurities with low and high molecular weights were completely removed. The molecular mass of rHWTX-I was identified as being 3750.8 Da, which was identical to natural HWTX-I with three disulfide bridges. Furthermore, by utilizing whole-cell patch clamp, the sodium currents of hNav1.7 could be inhibited by rHWTX-I and the IC50 value was 419 nmol/L.


Assuntos
Venenos de Aranha , Aranhas , Animais , Neurotoxinas/química , Neurotoxinas/farmacologia , Cisteína/metabolismo , Aranhas/química , Aranhas/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Venenos de Aranha/genética , Venenos de Aranha/química , Venenos de Aranha/metabolismo , Peptídeos/metabolismo , Dissulfetos/metabolismo
8.
Front Genet ; 13: 934683, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36035133

RESUMO

Background: Glioma is the most prevalent malignant intracranial tumor. Many studies have shown that angiogenesis plays a crucial role in glioma tumorigenesis, metastasis, and prognosis. In this study, we conducted a comprehensive analysis of angiogenesis-related genes (ARGs) in glioma. Methods: RNA-sequencing data of glioma patients were obtained from TCGA and CGGA databases. Via consensus clustering analysis, ARGs in the sequencing data were distinctly classified into two subgroups. We performed univariate Cox regression analysis to determine prognostic differentially expressed ARGs and least absolute shrinkage and selection operator Cox regression to construct a 14-ARG risk signature. The CIBERSORT algorithm was used to explore immune cell infiltration, and the ESTIMATE algorithm was applied to calculate immune and stromal scores. Results: We found that the 14-ARG signature reflected the infiltration characteristics of different immune cells in the tumor immune microenvironment. Additionally, total tumor mutational burden increased significantly in the high-risk group. We combined the 14-ARG signature with patient clinicopathological data to construct a nomogram for predicting 1-, 3-, and 5-year overall survival with good accuracy. The predictive value of the prognostic model was verified in the CGGA cohort. SPP1 was a potential biomarker of glioma risk and was involved in the proliferation, invasion, and angiogenesis of glioma cells. Conclusion: In conclusion, we established and validated a novel ARG risk signature that independently predicted the clinical outcomes of glioma patients and was associated with the tumor immune microenvironment.

9.
World J Clin Cases ; 10(13): 4249-4263, 2022 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-35665119

RESUMO

BACKGROUND: The coexistence of meningioma and other intracranial primary benign tumors is rare, especially in non-neurofibromatosis type 2, and there is limited guidance for the management of such patients. Here, we report a series of 5 patients with concomitant meningioma and other intracranial benign tumors, including subependymoma and pituitary adenoma. CASE SUMMARY: Five non-neurofibromatosis type 2 patients with simultaneous occurrence of meningioma and other intracranial benign tumors were retrospectively reviewed. The patients had no history of previous irradiation. The clinical features, pre- and postoperative imaging, surgical procedure and pathological findings were extracted from electronic medical records. There were 4 female patients (80%) and 1 male patient (20%). The mean age was 42.8 years (range: 29-52 years). The coexisting tumors included subependymoma in 1 case (20%) and pituitary adenoma in 4 cases (80%). The most common clinical symptom was headache (3/5, 60%). Four patients (80%) underwent craniotomy. One patient (20%) underwent transsphenoidal surgery followed by transcranial operation. All tumor diagnoses were confirmed by histopathological examination. The mean follow-up was 38.8 mo (range: 23-96 mo), and all 5 patients were in a stable condition at the last follow-up. CONCLUSION: The simultaneous occurrence of meningioma and other intracranial benign tumors is a rare clinical event. Histological examination is necessary for the accurate diagnosis. Neurosurgeons should select the appropriate surgical strategy according to the clinical features of each patient, which may provide a more favorable prognosis for individual patients.

10.
Front Surg ; 9: 916053, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35693315

RESUMO

Purpose: Patients with intraventricular tumors are more susceptible to postoperative meningitis (POM) than other intracranial tumors. In this study, we explored the risk factors of POM in lateral ventricular trigone meningiomas (LVTMs). Methods: Clinical features of 64 patients with LVTMs were analyzed. Age, gender, body mass index, medical history, intraoperative blood loss (IBL), intraventricular drainage placement, surgical duration, tumor grade, postoperative tumor cavity hemorrhage, and tumor size were included in univariate and multivariate analyses of POM. Results: Of the 64 patients, 14 patients (21.9%) received diagnosis of POM. The univariate analysis revealed IBL ≥400 mL (odds ratio [OR], 9.012; p = 0.003), tumor size ≥50 cm3 (OR, 3.071; p = 0.080), and surgical duration ≥5 h (OR, 2.970; p = 0.085) were considered possible risk factors for POM (p < 0.10). Tumor size (R = 0.514) and surgical duration (R = 0.624) were significantly correlated with IBL (p < 0.05). In the multivariate analysis, only IBL was found to be an independent risk factor for POM. Conclusion: The IBL ≥400 mL is independently associated with the increased risk of POM in LVTM patients. Our results demonstrate the importance of controlling IBL for preventing POM, especially in large tumors and long surgeries.

11.
Sensors (Basel) ; 22(7)2022 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-35408247

RESUMO

Aiming at the problem of Transformers lack of local spatial receptive field and discontinuous boundary loss in rotating object detection, in this paper, we propose a Transformer-based high-precision rotating object detection model (RODFormer). Firstly, RODFormer uses a structured transformer architecture to collect feature information of different resolutions to improve the collection range of feature information. Secondly, a new feed-forward network (spatial-FFN) is constructed. Spatial-FFN fuses the local spatial features of 3 × 3 depthwise separable convolutions with the global channel features of multilayer perceptron (MLP) to solve the deficiencies of FFN in local spatial modeling. Finally, based on the space-FFN architecture, a detection head is built using the CIOU-smooth L1 loss function and only returns to the horizontal frame when the rotating frame is close to the horizontal, so as to alleviate the loss discontinuity of the rotating frame. Ablation experiments of RODFormer on the DOTA dataset show that the Transformer-structured module, the spatial-FFN module and the CIOU-smooth L1 loss function module are all effective in improving the detection accuracy of RODFormer. Compared with 12 rotating object detection models on the DOTA dataset, RODFormer has the highest average detection accuracy (up to 75.60%), that is, RODFormer is more competitive in rotating object detection accuracy.

12.
Healthcare (Basel) ; 10(3)2022 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-35326992

RESUMO

The relationship between sleep posture and sleep quality has been studied comprehensively. Over 70% of chronic diseases are highly correlated with sleep problems. However, sleep posture monitoring requires professional devices and trained nursing staff in a medical center. This paper proposes a contactless sleep-monitoring Internet of Things (IoT) system that is equipped with a Raspberry Pi 4 Model B; radio-frequency identification (RFID) tags are embedded in bed sheets as part of a low-cost and low-power microsystem. Random forest classification (RFC) is used to recognize sleep postures, which are then uploaded to the server database via Wi-Fi and displayed on a terminal. The experimental results obtained using RFC were compared to those obtained via the support vector machine (SVM) method and the multilayer perceptron (MLP) algorithm to validate the performance of the proposed system. The developed system can be also applied for sleep self-management at home and wireless sleep monitoring in medical wards.

13.
Front Oncol ; 11: 748277, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34646781

RESUMO

PURPOSE: Multifocal and multicentric glioblastomas (mGBMs) are associated with a poorer prognosis compared to unifocal glioblastoma (uGBM). The presence of CD8+ tumor-infiltrating lymphocytes (TILs) is predictive of clinical outcomes in human malignancies. Here, we examined the CD8+ lymphocytic infiltration in mGBMs. METHODS: The clinical data of 57 consecutive IDH wildtype primary mGBM patients with histopathological diagnoses were retrospectively reviewed. CD8+ TILs were quantitatively evaluated by immunohistochemical staining. The survival function of CD8+ TILs was assessed by Kaplan-Meier analysis and Cox proportional hazard models. RESULTS: No significant difference in the concentration of CD8+ TILs was observed among foci from the same patient (P>0.150). The presence of CD8+ TILs was similar between multifocal and multicentric GBMs (P=0.885). The concentration of CD8+ TILs was significantly lower in mGBMs than in uGBMs (P=0.002). In mGBM patients, the CD8+ TIL level was associated with preoperative KPS (P=0.018). The median overall survival (OS) of the 57 mGBMs was 9 months. A low CD8+ TIL level (multivariate HR 4.404, 95% CI 1.954-9.926, P=0.0004) was an independent predictor of poor OS, while postoperative temozolomide chemotherapy (multivariate HR 6.076, 95% CI 2.330-15.842, P=0.0002) was independently associated with prolonged OS in mGBMs. CONCLUSIONS: Decreased CD8+ TIL levels potentially correlate with unfavorable clinical outcome in mGBMs, suggesting an influence of the local immuno-microenvironment on the progression of mGBMs.

14.
Oncogene ; 40(27): 4615-4624, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34131285

RESUMO

Mini-chromosome maintenance (MCM) proteins are critical components of DNA-replication-licensing factors. MCM8 is an MCM protein that exhibits oncogenic functions in several human malignancies. However, the role of MCM8 in glioblastomas (GBMs) has remained unclear. In the present study, we investigated the biological functions and mechanisms of MCM8 in glioma stem cells (GSCs). The clinical relevance of MCM8 mRNA expression was explored via TCGA and REMBRANDT datasets. The effects of MCM8 on the self-renewal and tumorigenicity of GSCs were examined both in vitro and in vivo. The regulation of MCM8 expression and its interacting proteins were also evaluated. We found that the expression of MCM8 was elevated in high-grade gliomas and classical molecular subtypes and was inversely correlated with patient prognosis. GSCs had a significantly higher expression of MCM8 compared with that in normal glioma cells. Silencing of MCM8 induced G0/G1 arrest and apoptosis, as well as inhibited the proliferation and self-renewal of GSCs. Forced expression of MCM8 enhanced clonogenicity of GSCs both in vitro and in vivo. MCM8 expression was regulated by EGFR signaling, which was mediated by NF-κB (p65). MCM8 interacted with DNA-replication-initiating factors-including EZH2, CDC6, and CDCA2-and influenced these factors to associate with chromatin. In addition, MCM8 knockdown increased the sensitivity of GSCs to radiation and TMZ treatments. Our findings suggest that MCM8, regulated by the EGFR pathway, maintains the clonogenic and tumorigenic potential of GSCs through interaction with DNA-replication-initiating factors; hence, MCM8 may represent a novel therapeutic target in GBMs.


Assuntos
Glioma , Oncogenes
15.
IEEE Trans Cybern ; 51(12): 5954-5968, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32149676

RESUMO

For social robots to effectively engage in human-robot interaction (HRI), they need to be able to interpret human affective cues and to respond appropriately via display of their own emotional behavior. In this article, we present a novel multimodal emotional HRI architecture to promote natural and engaging bidirectional emotional communications between a social robot and a human user. User affect is detected using a unique combination of body language and vocal intonation, and multimodal classification is performed using a Bayesian Network. The Emotionally Expressive Robot utilizes the user's affect to determine its own emotional behavior via an innovative two-layer emotional model consisting of deliberative (hidden Markov model) and reactive (rule-based) layers. The proposed architecture has been implemented via a small humanoid robot to perform diet and fitness counseling during HRI. In order to evaluate the Emotionally Expressive Robot's effectiveness, a Neutral Robot that can detect user affects but lacks an emotional display, was also developed. A between-subjects HRI experiment was conducted with both types of robots. Extensive results have shown that both robots can effectively detect user affect during the real-time HRI. However, the Emotionally Expressive Robot can appropriately determine its own emotional response based on the situation at hand and, therefore, induce more user positive valence and less negative arousal than the Neutral Robot.


Assuntos
Robótica , Teorema de Bayes , Comunicação , Emoções , Humanos , Interação Social
16.
Zootaxa ; 4877(1): zootaxa.4877.1.10, 2020 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-33311333

RESUMO

In this study, we describe one new species, Sichuana feicui He sp. nov., from Mao County, Sichuan Province, China. This new species is different from S. cryptospina in the shape of cercus, and the color pattern of hind femur. The type specimens are deposited in Museum of Biology, East China Normal University (ECNU).


Assuntos
Ortópteros , Distribuição Animal , Estruturas Animais , Animais , Tamanho Corporal , China , Masculino , Tamanho do Órgão
17.
Medicine (Baltimore) ; 99(44): e23028, 2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-33126391

RESUMO

RATIONALE: Tumor-to-tumor metastasis is a rare clinical phenomenon. Although meningioma is the most common intracranial recipient of cancer metastasis, only a few cases have been reported. We present a case of metastasis of lung adenocarcinoma into intracranial meningioma and review the published literature. PATIENT CONCERNS: A 70-year-old woman was admitted to our hospital for a 1-month history of headache and pain in her lower extremities. DIAGNOSIS: Brain and lumbar vertebral magnetic resonance imaging showed an intracranial space-occupying lesion in the right occipital region and spinal canal stenosis. Pulmonary computed tomography showed an irregular mass in the right upper lobe of the lung. The postoperative histological examination demonstrated adenocarcinoma metastasis to meningioma. INTERVENTION: The patient underwent right occipital craniotomy for tumor removal and lumbar spinal canal decompression. OUTCOMES: There were no initial abnormal conditions after the operation. However, the patient died suddenly 7 days after surgery. LESSONS: Tumor-to-meningioma metastasis is a rare but important phenomenon. According to previous reports, it is associated with rapid onset of symptoms and a poor prognosis. Histological examination is of great importance in diagnosis. The history and process of malignant carcinoma should be closely monitored.


Assuntos
Adenocarcinoma/diagnóstico , Neoplasias Pulmonares/diagnóstico , Neoplasias Meníngeas/diagnóstico , Meningioma/diagnóstico , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/secundário , Idoso , Craniotomia , Diagnóstico Diferencial , Feminino , Cefaleia/etiologia , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Neoplasias Meníngeas/complicações , Neoplasias Meníngeas/diagnóstico por imagem , Neoplasias Meníngeas/secundário , Meningioma/complicações , Meningioma/diagnóstico por imagem , Meningioma/secundário , Metástase Neoplásica , Lobo Occipital
18.
J Neurooncol ; 148(1): 179-186, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32333187

RESUMO

PURPOSE: Nonfunctional pituitary adenomas (NFPAs) in pediatric and adolescent age are extremely rare. This study aimed to report a series of 14 pediatric and adolescent NFPAs to assist in its clinical management. METHODS: A total of 14 consecutive patients pathologically diagnosed with NFPAs (age ≤ 20 years) were retrospectively examined, and the clinical data were analyzed. RESULTS: NFPA is uncommon in pediatric and adolescent patients (0.4%). The most common clinical symptoms were a headache (6/14, 42.9%) and visual loss (4/14, 28.6%). Ten patients (71.4%) had preoperative hypopituitarism. All patients were diagnosed with macroadenoma including 8 (57.1%) invasive tumors, and the average tumor diameter was 2.8 cm. All patients underwent transsphenoidal surgery, and a near-total resection was achieved in nine (64.3%) patients. Postoperative visual acuity improved in three patients (75%). The results of immunohistochemistry showed 6 silent plurihormonal adenomas (42.9%), 3 null cell adenomas (21.4%), 3 silent lactotroph adenomas (21.4%), 1 silent gonadotroph adenoma (7.1%) and 1 silent corticotroph adenoma (7.1%). The mean follow-up was 54.8 months, and five patients had tumor recurrence. Tumors with Ki-67 ≧ 2% (28.6%) showed higher recurrence rate than those with lower index (P = 0.001). Two patients received secondary surgery and radiation for recurrent tumors suffered from panhypopituitarism. CONCLUSION: Pediatric and adolescent NFPA is clinically rare, and shows potential invasiveness. The silent plurihormonal adenoma is the most frequent phenotype. Transsphenoidal surgery is as safe and effective as in adults. However, individualized care and teamwork of neurosurgeons, pediatricians, endocrinologists, and radiation oncologists are important, especially for recurrent diseases.


Assuntos
Adenoma/epidemiologia , Neoplasias Hipofisárias/epidemiologia , Adenoma/cirurgia , Adolescente , Adulto , Feminino , Humanos , Masculino , Neoplasias Hipofisárias/cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
19.
Theranostics ; 9(20): 6019-6030, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31534534

RESUMO

Background: Glioblastoma (GBM) is highly proliferative and resistant to radio-chemotherapy. Loss of tumor suppressor gene TP53 function frequently occurs at protein level in GBMs. This inhibition is often mediated by other components within the p53 signaling axis, including MDM2, whose binding protein (MTBP) plays an important role in the regulation of MDM2 and p53 activity. We investigated the role of MTBP in the biology of TP53-wildtype (TP53wt) GBMs. Methods: MTBP expression was examined in TCGA and REMBRANDT datasets. MTBP was silenced or overexpressed in TP53wt GBM cells and glioma stem cells (GSCs). The effects on cell viability, apoptosis, and clonogenicity were assessed. The transcriptional regulation of MTBP was investigated. Results: Upregulation of MTBP was correlated with the Classical molecular subtype, and it predicted poor survival. In TP53wt GBM cells, the protein levels of MTBP were positively associated with those of MDM2 but negatively correlated with those of p53. MTBP knockdown promoted apoptosis and inhibited clonogenicity, while overexpression of this protein enhanced tumorigenicity in vitro and in vivo. The pro-survival effect of MTBP depended on the activity of MDM2 and p53. MTBP was transcriptionally regulated by c-myc, thereby forming a positive regulatory loop. Finally, MTBP silencing increased the sensitivity of TP53wt GSCs to radiation and TMZ treatment in vitro and in vivo. Conclusion: MTBP regulates the cell survival and treatment sensitivity of TP53wt GBMs through MDM2-dependent post-translational modification of p53. MTBP-targeting treatments are potentially useful in increasing patients' survival.


Assuntos
Proteínas de Transporte/metabolismo , Glioblastoma/metabolismo , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Animais , Antineoplásicos Alquilantes/uso terapêutico , Apoptose/efeitos dos fármacos , Apoptose/genética , Apoptose/efeitos da radiação , Western Blotting , Proteínas de Transporte/genética , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Sobrevivência Celular/efeitos da radiação , Feminino , Citometria de Fluxo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos da radiação , Glioblastoma/tratamento farmacológico , Glioblastoma/genética , Glioblastoma/radioterapia , Glioma/genética , Glioma/metabolismo , Humanos , Imuno-Histoquímica , Imunoprecipitação , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Processamento de Proteína Pós-Traducional/genética , Processamento de Proteína Pós-Traducional/fisiologia , Proteínas Proto-Oncogênicas c-mdm2/genética , Reação em Cadeia da Polimerase em Tempo Real , Temozolomida/uso terapêutico , Proteína Supressora de Tumor p53/genética
20.
J Neurooncol ; 143(3): 563-571, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31087224

RESUMO

PURPOSE: Intracranial meningiomas are relatively rare in young adults, and their specific clinical features remain unclear. The authors analyzed the clinical characteristics of intracranial meningioma in patients younger than 40 years. METHODS: Consecutive patients younger than 40 years with meningioma (n = 223) who underwent surgical treatment at our hospital from 2010 to 2018 were retrospectively reviewed. The study cases was further divided into a younger group (≤ 30 years old; n = 63) and an older group (31-40 years old; n = 160). The clinical information, radiological characteristics, intraoperative findings, and pathological outcomes were extracted from the patients' records and statistically analyzed. RESULTS: Intracranial meningioma is uncommon in patients younger than 40 years (8.6%). The study group's most common symptoms at presentation were headaches (46.7%), visual impairment (27.8%), limb weakness (20.6%), and epilepsy (13.5%). The mean tumor size was larger (51.47 ± 50.36 cm3) in the younger group than in the older group (22.94 ± 27.20 cm3). According to multivariate analyses, young age was an independent predictor of large tumor size, and large tumor size was significantly associated with peritumoral brain edema and intraoperative blood loss. CONCLUSION: Intracranial meningiomas in younger adult patients may have special complexity and perioperative risk due to large tumor sizes. Therefore, individualized treatment strategy is recommended, and the appropriate caution should be taken during surgery.


Assuntos
Edema Encefálico/diagnóstico , Neoplasias Meníngeas/cirurgia , Meningioma/cirurgia , Procedimentos Neurocirúrgicos/efeitos adversos , Hemorragia Pós-Operatória/diagnóstico , Adolescente , Adulto , Fatores Etários , Edema Encefálico/etiologia , Criança , Feminino , Seguimentos , Humanos , Masculino , Neoplasias Meníngeas/patologia , Meningioma/patologia , Hemorragia Pós-Operatória/etiologia , Prognóstico , Estudos Retrospectivos , Adulto Jovem
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