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1.
Cancer Res Commun ; 4(8): 2203-2214, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39087378

RESUMEN

The role of mast cell (MC), a common myeloid-derived immune cell, in the development of oral squamous cell carcinoma (OSCC) is unclear. The aim of this study was to investigate MC infiltration in oral precancer and oral cancer. The evaluation of immune cell infiltration and its association with prognosis in OSCC used RNA sequencing and multiple public datasets. Multiplex immunofluorescence was used to explore the infiltration of MC in the microenvironment of OSCC and oral precancer and the interaction with CD8+ cells. The role of MC in OSCC progression was verified by in vivo experiments. The resting MC infiltration was mainly present in oral precancer, whereas activated MC infiltration was significantly higher in OSCC. Activated MC was associated with malignant transformation of oral precancer and poor prognosis of OSCC. In vivo studies showed that MC promoted the growth of OSCC. The infiltration of activated MC was negatively correlated with the infiltration of CD8+ T cells. The subtype of MC containing tryptase without chymase (MCT) was significantly higher in OSCC compared with oral precancer and was associated with poor survival. Furthermore, spatial distance analysis revealed a greater distance between MCT and CD8+ cells, which was also linked to poor prognosis in OSCC. Cox regression analysis showed that MCT could be a potential diagnostic and prognostic biomarker. This study provides new insights into the role of MC in the immune microenvironment of OSCC. It might enhance the immunotherapeutic efficacy of OSCC by developing targeted therapies against MC. SIGNIFICANCE: In this study, we investigated the role of mast cells (MC) in oral precancer and oral cancer and demonstrated that MCs are involved in oral cancer progression and may serve as a potential diagnostic and prognostic marker. It might improve the immunotherapeutic efficacy through developing targeted therapies against MCs.


Asunto(s)
Transformación Celular Neoplásica , Progresión de la Enfermedad , Mastocitos , Neoplasias de la Boca , Lesiones Precancerosas , Microambiente Tumoral , Mastocitos/patología , Mastocitos/inmunología , Neoplasias de la Boca/patología , Neoplasias de la Boca/inmunología , Neoplasias de la Boca/mortalidad , Humanos , Microambiente Tumoral/inmunología , Transformación Celular Neoplásica/inmunología , Transformación Celular Neoplásica/patología , Lesiones Precancerosas/patología , Lesiones Precancerosas/inmunología , Pronóstico , Animales , Linfocitos T CD8-positivos/inmunología , Ratones , Masculino , Triptasas/metabolismo , Triptasas/genética , Femenino , Quimasas/metabolismo , Quimasas/genética , Linfocitos Infiltrantes de Tumor/inmunología , Linfocitos Infiltrantes de Tumor/patología
2.
ACS Nano ; 18(33): 21873-21885, 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-39115266

RESUMEN

The silicon nanowire field-effect transistor (SiNW FET) has been developed for over two decades as an ultrasensitive, label-free biosensor for biodetection. However, inconsistencies in manufacturing and surface functionalization at the nanoscale have led to poor sensor-to-sensor consistency in performance. Despite extensive efforts to address this issue through process improvements and calibration methods, the outcomes have not been satisfactory. Herein, based on the strong correlation between the saturation response of SiNW FET biosensors and both their feature size and surface functionalization, we propose a calibration strategy that combines the sensing principles of SiNW FET with the Langmuir-Freundlich model. By normalizing the response of the SiNW FET biosensors (ΔI/I0) with their saturation response (ΔI/I0)max, this strategy fundamentally overcomes the issues mentioned above. It has enabled label-free detection of nucleic acids, proteins, and exosomes within 5 min, achieving detection limits as low as attomoles and demonstrating a significant reduction in the coefficient of variation. Notably, the nucleic acid test results exhibit a strong correlation with the ultraviolet-visible (UV-vis) spectrophotometer measurements, with a correlation coefficient reaching 0.933. The proposed saturation response calibration strategy exhibits good universality and practicability in biological detection applications, providing theoretical and experimental support for the transition of mass-manufactured nanosensors from theoretical research to practical application.


Asunto(s)
Técnicas Biosensibles , Nanocables , Silicio , Transistores Electrónicos , Silicio/química , Técnicas Biosensibles/instrumentación , Nanocables/química , Calibración , Ácidos Nucleicos/análisis
3.
NPJ Metab Health Dis ; 2(1): 20, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39149696

RESUMEN

Histone deacetylases (HDACs) have a wide range of targets and can rewire both the chromatin and lipidome of cancer cells. In this study, we show that valproic acid (VPA), a brain penetrant anti-seizure medication and histone deacetylase inhibitor, inhibits the growth of IDH1 mutant tumors in vivo and in vitro, with at least some selectivity over IDH1 wild-type tumors. Surprisingly, genes upregulated by VPA showed no enhanced chromatin accessibility at the promoter, but there was a correlation between VPA-downregulated genes and diminished promoter chromatin accessibility. VPA inhibited the transcription of lipogenic genes and these lipogenic genes showed significant decreases in promoter chromatin accessibility only in the IDH1 MT glioma cell lines tested. VPA inhibited the mTOR pathway and a key lipogenic gene, fatty acid synthase (FASN). Both VPA and a selective FASN inhibitor TVB-2640 rewired the lipidome and promoted apoptosis in an IDH1 MT but not in an IDH1 WT glioma cell line. We further find that HDACs are involved in the regulation of lipogenic genes and HDAC6 is particularly important for the regulation of FASN in IDH1 MT glioma. Finally, we show that FASN knockdown alone and VPA in combination with FASN knockdown significantly improved the survival of mice in an IDH1 MT primary orthotopic xenograft model in vivo. We conclude that targeting fatty acid metabolism through HDAC inhibition and/or FASN inhibition may be a novel therapeutic opportunity in IDH1 mutant gliomas.

4.
Artículo en Inglés | MEDLINE | ID: mdl-39093351

RESUMEN

Helicases, which utilize ATP hydrolysis to separate nucleic acid duplexes, play crucial roles in DNA and RNA replication, repair, recombination, and transcription. Categorized into the major groups superfamily 1 (SF1) and superfamily 2 (SF2), alongside four minor groups, these proteins exhibit a conserved catalytic core indicative of a shared evolutionary origin while displaying functional diversity through interactions with various substrates. This review summarizes the structures, functions and mechanisms of SF1 and SF2 helicases, with an emphasis on conserved ATPase sites and RecA-like domains essential for their enzymatic and nucleic acid binding capabilities. It highlights the unique 1B and 2B domains in SF1 helicases and their impact on enzymatic activity. The DNA unwinding process is detailed, covering substrate recognition, ATP hydrolysis, and conformational changes, while addressing debates over the active form of UvrD helicase and post-unwinding dissociation. More importantly, this review discusses the biotechnological potential of helicases in emerging technologies such as nanopore sequencing, protein sequencing, and isothermal amplification, focusing on their use in pathogen detection, biosensor enhancement, and cancer treatment. As understanding deepens, innovative applications in genome editing, DNA sequencing, and synthetic biology are anticipated.

5.
Front Genet ; 15: 1377716, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39135681

RESUMEN

Background: There is inconsistent evidence regarding the accuracy of GNAS mutations identification for the diagnosis of FD/MAS. This study was performed to estimate the prevalence and diagnostic accuracy of GNAS mutations detection and to preliminarily investigate the genotype-phenotype correlation in FD patients. Methods: Five electronic databases were searched from 1995 to 2024 using search terms related to GNAS and fibrous dysplasia. Observational studies of FD patients undergoing GNAS mutation detection in FD were included. Results: A total of 878 FD patients were included. The pooled prevalence of GNAS mutations in FD based on the random effects model was 74% (95% CI = 64%-83%). Regarding diagnostic accuracy, a sensitivity of 0.83 (95% CI, 0.65-0.96), specificity of 0.99 (95% CI, 0.98-1.00) and the area under the receiver operating characteristic curve of 98.38% were found. Additionally, meta-analysis and Fisher's test showed the GNAS mutation types were significantly associated with FD types (OR = 3.51, 95% CI = 1.05 to 11.72; p < 0.05). Conclusion: A high detection rate of GNAS mutations occurred in FD, and its detection is reliable for diagnosing FD. Additionally, GNAS mutation type was types were significantly associated with FD type. Systematic Review Registration: Identifier CRD42024553469.

6.
Microsyst Nanoeng ; 10: 98, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39015941

RESUMEN

Flexible sensors are essential components in emerging fields such as epidermal electronics, biomedicine, and human-computer interactions, and creating high-performance sensors through simple structural design for practical applications is increasingly needed. Presently, challenges still exist in establishing efficient models of flexible piezoresistive pressure sensors to predict the design required for achieving target performance. This work establishes a theoretical model of a flexible pressure sensor with a simple laminated and enclosed structure. In the modeling, the electrical constriction effect is innovatively introduced to explain the sensitization mechanism of the laminated structure to a broad range of pressures and to predict the sensor performance. The experimental results confirmed the effectiveness of the theoretical model. The sensor exhibited excellent stability for up to three million cycles and superior durability when exposed to salt solution owing to its simple laminated and enclosed structural design. Finally, a wearable sensing system for real-time collection and analysis of plantar pressure is constructed for exercise and rehabilitation monitoring applications. This work aims to provide theoretical guidance for the rapid design and construction of flexible pressure sensors with target performance for practical applications.

7.
ACS Appl Mater Interfaces ; 16(28): 36577-36585, 2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-38972068

RESUMEN

Tin oxide is a promising channel material, offering the advantages of being low-cost and environmentally friendly and having a wide band gap. However, despite the high electron mobility of SnO2 in bulk, the corresponding thin-film transistors (TFTs) generally exhibit moderate performance, hindering their widespread application. Herein, we proposed a codoping strategy to improve both the electrical property and the stability of SnO2 TFTs. A comparative analysis between doped and undoped SnO2 was conducted. It is observed that taking advantage of the difference in ionic radii between two dopants (indium and gallium) and the tin ions in the host lattice can effectively reduce impurity-induced strain. Additionally, we investigated the effect of codoping content on SnO2 TFTs. The optimal codoped SnO2 (TIGO) TFTs demonstrate high performance, featuring a field-effect mobility of 15.9 cm2/V·s, a threshold voltage of 0.2 V, a subthreshold swing of 0.5 V/decade, and an on-to-off current ratio of 2.2 × 107. Furthermore, the devices show high stability under both positive and negative bias stress conditions with a small threshold voltage shift of 1.8 and -1.2 V, respectively. Utilizing the TIGO TFTs, we successfully constructed a resistor-loaded unipolar inverter with a high gain of 10.76. This study highlights the potential of codoped SnO2 TFTs for advanced applications in electronic devices.

8.
J Tradit Complement Med ; 14(4): 446-455, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39035685

RESUMEN

Background and aim: The most effective among the acupoints remains to be determined for treating diabetic gastroparesis (DGP). This study aimed to compare single and combination acupoints for their effectiveness in DGP. Experimental procedure: A prospective, patient-assessor-blinded randomised controlled trial was designed to compare the efficacy of 8-week acupuncture at a single acupoint (Zhongwan, CV-12), combination acupoints (Zhongwan, CV-12 and Zusanli, ST-36), and a sham-acupoint, in 99 adults with DGP. The primary clinical outcome was measured using the Gastroparesis Cardinal Symptom Index (GCSI), while barium meal examination, fasting plasma glucose, the 2-h plasma glucose, short-form health survey (SF-36), and GCSI subscales were performed for evaluating secondary clinical outcomes. These results were analysed by two factorial analysis of variance (ANOVA) test, Chi-Square, Fisher Exact, Kruskal-Wallis tests and Tukey's Honest Significant Difference (HSD) test. Results: After randomization, 97 patients completed the study. GCSI scores of all groups decreased during both post-treatment and the follow-up period, they were statistically significant compared to the baseline period (p < 0.01), but there was no significant difference among the groups (p > 0.05) during the post-treatment period. GCSI scores improved more in the combination acupoints group than in the single acupoint group which was better than the sham group after treatment. During the follow-up period, the same trend was observed. Conclusions: Among patients with DGP, the combination acupoints were more beneficial compared with single and sham acupoints. Trial registration number: NCT02452489.

9.
Medicine (Baltimore) ; 103(28): e38823, 2024 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-38996127

RESUMEN

Endometriosis, identified by the abnormal growth of endometrial cells beyond the inner lining of the uterus, often manifests through symptoms like painful menstruation and challenges in conceiving. Observational studies suggest that endometriosis is often comorbid with mental disorders, including anxiety and depression. The nature of these connections, whether they are causal, is still debated and calls for further empirical evidence. We utilized a bidirectional 2-sample Mendelian randomization (MR) approach, harnessing genome-wide association study data to explore the connections among depression, anxiety, neuroticism, and endometriosis. To scrutinize the causative connections between mental health issues and endometriosis, Inverse Variance Weighting (IVW) was employed as the primary analytical tool, complemented by Weighted Median Estimation, Simple mode, Weighted mode, and MR-Egger regression for additional analysis. To examine the potential for reverse causation, reverse MR was applied. To strengthen the reliability of our findings, we carried out sensitivity analyses that included heterogeneity tests, tests for pleiotropy, and leave-one-out analyses. The IVW analysis revealed a significant correlation between the genetic inclination towards depression and a heightened risk of developing endometriosis [Odds Ratio (OR) = 1.151, 95% Confidence Interval (CI) = 1.025-1.293, P = .017]. Similarly, a genetic predisposition to neuroticism was significantly associated with an increased risk of endometriosis (OR = 1.128, 95% CI = 1.038-1.226, P = .004). However, no causative link was found between genetic susceptibility to anxiety and the occurrence of endometriosis. Reverse MR analysis did not support a bidirectional genetic susceptibility between endometriosis and psychiatric disorders. The MR analysis presents genetic data supporting the notion that depression and neuroticism are risk factors for endometriosis. Conversely, it found no evidence of a causal connection between anxiety and the development of endometriosis. Enhancing mental health treatment should be considered a preventive measure against endometriosis.


Asunto(s)
Ansiedad , Depresión , Endometriosis , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Neuroticismo , Humanos , Endometriosis/genética , Endometriosis/epidemiología , Femenino , Depresión/epidemiología , Depresión/etiología , Ansiedad/epidemiología , Predisposición Genética a la Enfermedad
10.
Zhongguo Zhen Jiu ; 44(7): 838-44, 2024 Jul 12.
Artículo en Chino | MEDLINE | ID: mdl-38986598

RESUMEN

This article summarizes and discusses the collaborative effects of acupuncture and medication in treatment, including four aspects, named "acupuncture synergizing the effects of medication", "medication advancing the effects of acupuncture", "coordination of acupuncture and medication", and "antagonism of acupuncture and medication". Regarding "acupuncture synergizing the effects of medication", the actions of acupuncture are predominant, which affects the absorption and metabolism of drugs in the body, increases drug concentration in blood, enhances the targeting effect of drugs, guides meridian tropism, alleviates the drug dose and adverse reactions, avoids the first pass effect and accelerates the drug bioavailability. As for "medication advancing the effects of acupuncture", the synergistic effect of acupuncture is obtained by medication, besides, the medication itself may supplement the drug property to the needles during acupuncture pretreatment so as to increase the therapeutic effect. In terms of "coordination of acupuncture and medication", and "antagonism of acupuncture and medication", there are the underlying co-effects of acupuncture and medication in the body, and the action targets may be same or different between them, thus, it needs to be further explored.


Asunto(s)
Terapia por Acupuntura , Humanos , Terapia Combinada
11.
Brain Behav ; 14(7): e3613, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38970224

RESUMEN

BACKGROUND: Central nervous system (CNS) disorders, such as stroke, often lead to spasticity, which result in limb deformities and significant reduction in quality of life. Spasticity arises from disruptions in the normal functioning of cortical and descending inhibitory pathways in the brainstem, leading to abnormal muscle contractions. Contralateral seventh cervical nerve cross transfer (CC7) surgery has been proven to effectively reduce spasticity, but the specific mechanism for its effectiveness is unclear. METHODS: This study aimed to investigate the changes in the dorsal root ganglia (DRG) following CC7 surgery. A comprehensive anatomical analysis was conducted through cadaveric study and magnetic resonance imaging (MRI) study, to accurately measure the regional anatomy of the C7 DRG. DRG perfusion changes were quantitatively assessed by comparing pre- and postoperative dynamic contrast-enhanced (DCE) MRI. RESULTS: In CC7 surgery, the C7 nerve root on the affected side is cut close to the DRG (3.6 ± 1.0 mm), while the C7 nerve root on the healthy side is cut further away from the DRG (65.0 ± 10.0 mm). MRI studies revealed that after C7 proximal neurotomy on the affected side, there was an increase in DRG volume, vascular permeability, and perfusion; after C7 distal neurotomy on the healthy side, there was a decrease in DRG volume, with no significant changes in vascular permeability and perfusion. CONCLUSION: This study provides preliminary insights into the mechanisms of spasticity reduction following CC7 surgery, indicating that changes in the DRG, such as increased vascular permeability and perfusion, could disrupt abnormal spinal γ-circuits. The resulting high-perfusion state of DRG, possibly due to heightened neuronal activity and metabolic demands, necessitating further research to verify this hypothesis.


Asunto(s)
Ganglios Espinales , Imagen por Resonancia Magnética , Espasticidad Muscular , Espasticidad Muscular/cirugía , Espasticidad Muscular/fisiopatología , Ganglios Espinales/diagnóstico por imagen , Ganglios Espinales/cirugía , Ganglios Espinales/fisiopatología , Humanos , Masculino , Femenino , Transferencia de Nervios/métodos , Cadáver , Persona de Mediana Edad , Anciano , Raíces Nerviosas Espinales/cirugía , Raíces Nerviosas Espinales/diagnóstico por imagen , Raíces Nerviosas Espinales/fisiopatología
12.
Clin Exp Med ; 24(1): 149, 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38967892

RESUMEN

Irritable bowel syndrome (IBS) is a common chronic gastrointestinal disorder, but its diagnosis and treatment remain obscure. Non-coding RNAs (ncRNAs), as potential biomarkers, have attracted increasing attention in digestive diseases. Here, we present a comprehensive research status, development trends, and valuable insights in this subject area. The literature search was performed using Web of Science Core Collection. VOSviewer 1.6.20, Citespace 6.2.R4, and Microsoft Excel 2021 were used for bibliometric analysis. A total of 124 articles were included in the analysis. Overall, publication patterns fluctuated. Globally, People's Republic of China, the USA, and Germany were the top three contributors of publications. Guangzhou University of Chinese Medicine, University of California, Mayo Clinic, and University of California, Los Angeles contributed the highest number of publications. The pathways and specific mechanisms by which ncRNAs regulate transcription and translation and thus regulate the pathophysiological processes of IBS are the main research hotspots in this field. We found that microRNA (miRNAs) are intricately involved in the regulation of key pathologies such as viscera sensitivity, intestinal permeability, intestinal mucosal barrier, immunoinflammatory response, and brain-gut axis in the IBS, and these topics have garnered significant attention in research community. Notably, microecological disorders are also associated with IBS pathogenesis, and ncRNA may play an important role in the interactions between host and intestinal flora. This is the first bibliometric study to comprehensively summarize the research hotspots and trends related to IBS and ncRNAs (especially miRNAs). Our findings will help understand the role of ncRNAs in IBS and provide guidance to future studies.


Asunto(s)
Bibliometría , Síndrome del Colon Irritable , MicroARNs , Humanos , Síndrome del Colon Irritable/genética , MicroARNs/genética
13.
Front Endocrinol (Lausanne) ; 15: 1397402, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38872962

RESUMEN

Graphene-based warm uterus acupoint paste (GWUAP) is an emerging non-drug alternative therapy for the treatment of primary dysmenorrhea (PD), but the underlying mechanism is still unclear. SD female rats were randomly divided into control group, model group and treatment group to explore the mechanism of GWUAP in the treatment of PD. Combined with 16S rDNA and fecal metabolomics, the diversity of microbiota and metabolites in each group was comprehensively evaluated. In this study, GWUAP reduced the torsion score of PD model rats, improved the pathological morphology of uterine tissue, reduced the pathological damage score of uterine tissue, and reversed the expression levels of inflammatory factors, pain factors and sex hormones. The 16 S rDNA sequencing of fecal samples showed that the abundance of Lactobacillus in the intestinal flora of the model group decreased and the abundance of Romboutsia increased, while the abundance of Lactobacillus in the intestinal flora of the treatment group increased and the abundance of Romboutsia decreased, which improved the imbalance of flora diversity in PD rats. In addition, 32 metabolites related to therapeutic effects were identified by metabolomics of fecal samples. Moreover, there is a close correlation between fecal microbiota and metabolites. Therefore, the mechanism of GWUAP in the treatment of PD remains to be further studied.


Asunto(s)
Puntos de Acupuntura , Dismenorrea , Metabolómica , Ratas Sprague-Dawley , Animales , Femenino , Dismenorrea/terapia , Dismenorrea/tratamiento farmacológico , Ratas , Microbioma Gastrointestinal/efectos de los fármacos , ARN Ribosómico 16S/genética , Heces/microbiología , ADN Ribosómico/genética
14.
Eur J Neurosci ; 60(3): 4254-4264, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38830753

RESUMEN

Left hemisphere injury can cause right spastic arm paralysis and aphasia, and recovery of both motor and language functions shares similar compensatory mechanisms and processes. Contralateral cervical seventh cross transfer (CC7) surgery can provide motor recovery for spastic arm paralysis by triggering interhemispheric plasticity, and self-reports from patients indicate spontaneous improvement in language function but still need to be verified. To explore the improvements in motor and language function after CC7 surgery, we performed this prospective observational cohort study. The Upper Extremity part of Fugl-Meyer scale (UEFM) and Modified Ashworth Scale were used to evaluate motor function, and Aphasia Quotient calculated by Mandarin version of the Western Aphasia Battery (WAB-AQ, larger score indicates better language function) was assessed for language function. In 20 patients included, the average scores of UEFM increased by .40 and 3.70 points from baseline to 1-week and 6-month post-surgery, respectively. The spasticity of the elbow and fingers decreased significantly at 1-week post-surgery, although partially recurred at 6-month follow-up. The average scores of WAB-AQ were increased by 9.14 and 10.69 points at 1-week and 6-month post-surgery (P < .001 for both), respectively. Post-surgical fMRI scans revealed increased activity in the bilateral hemispheres related to language centrals, including the right precentral cortex and right gyrus rectus. These findings suggest that CC7 surgery not only enhances motor function but may also improve the aphasia quotient in patients with right arm paralysis and aphasia due to left hemisphere injuries.


Asunto(s)
Afasia , Transferencia de Nervios , Humanos , Femenino , Masculino , Persona de Mediana Edad , Afasia/etiología , Afasia/fisiopatología , Adulto , Transferencia de Nervios/métodos , Estudios Prospectivos , Imagen por Resonancia Magnética/métodos , Anciano , Brazo/fisiopatología , Recuperación de la Función/fisiología , Encéfalo/fisiopatología , Encéfalo/diagnóstico por imagen , Espasticidad Muscular/cirugía , Espasticidad Muscular/fisiopatología , Espasticidad Muscular/etiología
15.
Cancer Res Commun ; 4(7): 1834-1849, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38856710

RESUMEN

Glioblastoma (GBM) is the most common malignant primary brain tumor and remains incurable. Previous work has shown that systemic administration of Decitabine (DAC) induces sufficient expression of cancer-testis antigens (CTA) in GBM for targeting by adoptive T-cell therapy in vivo. However, the mechanisms by which DAC enhances immunogenicity in GBM remain to be elucidated. Using New York esophageal squamous cell carcinoma 1 (NY-ESO-1) as a representative inducible CTA, we demonstrate in patient tissue, immortalized glioma cells, and primary patient-derived gliomaspheres that basal CTA expression is restricted by promoter hypermethylation in gliomas. DAC treatment of glioma cells specifically inhibits DNA methylation silencing to render NY-ESO-1 and other CTA into inducible tumor antigens at single-cell resolution. Functionally, NY-ESO-1 T-cell receptor-engineered effector cell targeting of DAC-induced antigen in primary glioma cells promotes specific and polyfunctional T-cell cytokine profiles. In addition to induction of CTA, DAC concomitantly reactivates tumor-intrinsic human endogenous retroviruses, interferon response signatures, and MHC-I. Overall, we demonstrate that DAC induces targetable tumor antigen and enhances T-cell functionality against GBM, ultimately contributing to the improvement of targeted immune therapies in glioma. SIGNIFICANCE: This study dissects the tumor-intrinsic epigenetic and transcriptional mechanisms underlying enhanced T-cell functionality targeting decitabine-induced cancer-testis antigens in glioma. Our findings demonstrate concomitant induction of tumor antigens, reactivation of human endogenous retroviruses, and stimulation of interferon signaling as a mechanistic rationale to epigenetically prime human gliomas to immunotherapeutic targeting.


Asunto(s)
Antígenos de Neoplasias , Neoplasias Encefálicas , Decitabina , Retrovirus Endógenos , Epigénesis Genética , Glioma , Humanos , Antígenos de Neoplasias/inmunología , Antígenos de Neoplasias/genética , Decitabina/farmacología , Decitabina/uso terapéutico , Glioma/inmunología , Glioma/genética , Retrovirus Endógenos/genética , Neoplasias Encefálicas/inmunología , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Metilación de ADN , Línea Celular Tumoral , Análisis de la Célula Individual , Regulación Neoplásica de la Expresión Génica , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Regiones Promotoras Genéticas , Glioblastoma/inmunología , Glioblastoma/genética , Glioblastoma/patología
16.
Toxics ; 12(6)2024 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-38922084

RESUMEN

To understand the influences of emulsified fuel on ship exhaust emissions more comprehensively, the emissions of particulate matter (PM), nitrated, oxygenated and parent polycyclic aromatic hydrocarbons (PAHs) were studied on a ship main engine burning emulsified heavy fuel oil (EHFO) and heavy fuel oil (HFO) as a reference. The results demonstrate that EHFO (emulsified heavy fuel oil) exhibits notable abilities to significantly reduce emissions of particulate matter (PM) and low molecular weight PAHs (polycyclic aromatic hydrocarbons) in the gas phase, particularly showcasing maximum reductions of 13.99% and 40.5%, respectively. Nevertheless, burning EHFO could increase the emission of high molecular weight PAHs in fine particles and pose a consequent higher carcinogenic risk for individual particles. The total average (gaseous plus particulate) ΣBEQ of EHFO exhausts (41.5 µg/m3) was generally higher than that of HFO exhausts (18.7 µg/m3). Additionally, the combustion of EHFO (extra-heavy fuel oil) can significantly alter the emission quantity, composition, and particle-size distribution of PAH derivatives. These changes may be linked to molecular structures, such as zigzag configurations in C=O bonds. Our findings may favor the comprehensive environmental assessments on the onboard application of EHFO.

17.
Artículo en Inglés | MEDLINE | ID: mdl-38896394

RESUMEN

The proliferation and differentiation of skeletal muscle satellite cells is a complex physiological process involving various transcription factors and small RNA molecules. This study aimed to understand the regulatory mechanisms underlying these processes, focusing on interferon-related development factor 2 (IFRD2) as a target gene of miRNA-2400 in bovine skeletal MuSCs (MuSCs). IFRD2 was identified as a target gene of miRNA-2400 involved in regulating the proliferation and differentiation of bovine skeletal MuSCs. Our results indicate that miR-2400 can target binding the 3'UTR of IFRD2 and inhibit its translation. mRNA and protein expression levels of IFRD2 increased significantly with increasing days of differentiation. Moreover, overexpression of the IFRD2 gene inhibited proliferation and promoted differentiation of bovine MuSCs. Conversely, the knockdown of the gene had the opposite effect. Overexpression of IFRD2 resulted in the inhibition of ERK1/2 phosphorylation levels in bovine MuSCs, which in turn promoted differentiation. In summary, IFRD2, as a target gene of miR-2400, crucially affects bovine skeletal muscle proliferation and differentiation by precisely regulating ERK1/2 phosphorylation.

18.
Oral Dis ; 2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38813877

RESUMEN

OBJECTIVE: In this study, our aim was to develop and validate the effectiveness of diverse radiomic models for distinguishing between gnathic fibrous dysplasia (FD) and ossifying fibroma (OF) before surgery. MATERIALS AND METHODS: We enrolled 220 patients with confirmed FD or OF. We extracted radiomic features from nonenhanced CT images. Following dimensionality reduction and feature selection, we constructed radiomic models using logistic regression, support vector machine, random forest, light gradient boosting machine, and eXtreme gradient boosting. We then identified the best radiomic model using receiver operating characteristic (ROC) curve analysis. After combining radiomics features with clinical features, we developed a comprehensive model. ROC curve and decision curve analysis (DCA) demonstrated the models' robustness and clinical value. RESULTS: We extracted 1834 radiomic features from CT images, reduced them to eight valuable features, and achieved high predictive efficiency, with area under curves (AUC) exceeding 0.95 for all the models. Ultimately, our combined model, which integrates radiomic and clinical data, displayed superior discriminatory ability (AUC: training cohort 0.970; test cohort 0.967). DCA highlighted its optimal clinical efficacy. CONCLUSION: Our combined model effectively differentiates between FD and OF, offering a noninvasive and efficient approach to clinical decision-making.

19.
J Oral Pathol Med ; 53(6): 393-403, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38777565

RESUMEN

OBJECTIVE: This Bayesian network meta-analysis was performed to analyze the associations between clinicopathological characteristics and BRAF mutations in ameloblastoma (AM) patients and to evaluate the diagnostic accuracy. MATERIALS AND METHODS: Four electronic databases were searched from 2010 to 2024. The search terms used were specific to BRAF and AM. Observational studies or randomized controlled trials were considered eligible. The incidence of BRAF mutation and corresponding clinicopathological features in AM patients were subjected to Bayesian network analyses and diagnostic accuracy evaluation. RESULTS: A total of 937 AM patients from 20 studies were included. The pooled prevalence of BRAF mutations in AM patients was 72%. According to the Bayesian network analysis, BRAF mutations are more likely to occur in younger (odds ratio [OR], 2.3; credible interval [CrI]: 1.2-4.5), mandible site (OR, 3.6; 95% CrI: 2.7-5.2), and unicystic (OR, 1.6; 95% CrI: 1.1-2.4) AM patients. Similarly, higher diagnostic accuracy was found in the younger, mandible, and unicystic AM groups. CONCLUSIONS: The incidence, risk, and diagnostic accuracy of BRAF mutation in AM were greater in younger patients, those with mandible involvement, and those with unicystic AM than in patients with other clinicopathological features. In addition, there was a strong concordance in the diagnostic accuracy between molecular tests and immunohistochemical analysis.


Asunto(s)
Ameloblastoma , Teorema de Bayes , Mutación , Proteínas Proto-Oncogénicas B-raf , Ameloblastoma/genética , Ameloblastoma/patología , Humanos , Proteínas Proto-Oncogénicas B-raf/genética , Neoplasias Maxilomandibulares/genética , Neoplasias Maxilomandibulares/patología , Metaanálisis en Red , Masculino , Femenino , Adulto , Persona de Mediana Edad
20.
Int J Biol Macromol ; 269(Pt 1): 132015, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38697432

RESUMEN

This study aimed to compare the effects of pectin and hydrolyzed pectin coating as pre-frying treatments on acrylamide content and quality characteristics of fried potato chips. The hydrolyzed pectin with molecular weight (Mw) of 8.81 ± 0.49 kDa was obtained through partial degradation of pectin (Mw: 747.57 ± 6.73 kDa) using pectinase. Results showed that both pectin and hydrolyzed pectin coating significantly inhibited acrylamide formation and inhibition rates exceeded 90 %. Hydrolyzed pectin had stronger inhibitory activity against acrylamide formation than pectin, especially when the concentration of hydrolyzed pectin was >2 %, its inhibitory rate exceeded 95 %. Compared to pectin coating, hydrolyzed pectin coating endow fried potato chips with smaller browning, higher crispness, less moisture but higher oil content. Overall, hydrolyzed pectin had better application prospects than pectin in inhibiting acrylamide formation of fried potato chips.


Asunto(s)
Acrilamida , Pectinas , Solanum tuberosum , Solanum tuberosum/química , Pectinas/química , Acrilamida/química , Hidrólisis , Culinaria , Peso Molecular
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