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1.
Clin Rheumatol ; 2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-38961031

RESUMEN

The burden of osteoarthritis (OA) is rapidly increasing with population aging, but there are still no approved disease-modifying drugs available. Accumulating evidence has shown that OA is a heterogeneous disease with multiple phenotypes, and it is unlikely to respond to one-size-fits-all treatments. Inflammation is recognized as an important phenotype of OA and is associated with worse pain and joint deterioration. Therefore, it is believed that anti-inflammatory treatments may be more effective for OA with an inflammatory phenotype. In this review, we summarized clinical trials that evaluated anti-inflammatory treatments for OA and discussed whether these treatments are more effective in inflammatory OA phenotypes compared to general OA patients.

2.
Methods Mol Biol ; 2829: 175-183, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38951333

RESUMEN

Monoclonal antibodies have widespread applications in disease treatment and antigen detection. They are traditionally produced using mammalian cell expression system, which is not able to satisfy the increasing demand of these proteins at large scale. Baculovirus expression vector system (BEVS) is an attractive alternative platform for the production of biologically active monoclonal antibodies. In this chapter, we demonstrate the production of an HIV-1 broadly neutralizing antibody b12 in BEVS. The processes including transfer vector construction, recombinant baculovirus generation, and antibody production and detection are described.


Asunto(s)
Baculoviridae , Vectores Genéticos , Baculoviridae/genética , Vectores Genéticos/genética , Animales , Humanos , Expresión Génica , VIH-1/genética , VIH-1/inmunología , Proteínas Recombinantes/genética , Proteínas Recombinantes/biosíntesis , Anticuerpos Monoclonales/genética , Anticuerpos Monoclonales/biosíntesis , Anticuerpos Monoclonales/inmunología , Anticuerpos Neutralizantes/inmunología , Ensayo de Inmunoadsorción Enzimática , Anticuerpos Anti-VIH/inmunología , Anticuerpos Anti-VIH/genética , Células Sf9
3.
Methods Mol Biol ; 2829: 267-270, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38951342

RESUMEN

There are many methods that can be used to determine the infectious titer of your baculovirus stock. The TCID50 method is a simple end-point dilution method that determines the amount of baculovirus virus needed to produce a cytopathic effect or kill 50% of inoculated insect cells. Serial dilutions of baculovirus stock are added to Sf9 cells cultivated in 96-well plates and 3-5 days after infection, cells are monitored for cell death or cytopathic effect. The titer can then be calculated by the Reed-Muench method as described in this method.


Asunto(s)
Baculoviridae , Baculoviridae/genética , Animales , Células Sf9 , Efecto Citopatogénico Viral , Spodoptera/virología , Carga Viral/métodos , Línea Celular
4.
ACS Appl Mater Interfaces ; 16(25): 32425-32433, 2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-38865279

RESUMEN

The application potential of ferroelectric thin films largely relies on the controllability of their domain structure. Among the various proposed strategies, mechanical switching is being considered as a potential alternative to replace electrical switching for control of the domain structure of ferroelectric thin films via, e.g., the flexoelectric effect. So far, studies on mechanical switching are confined to out-of-plane polarization switching in ferroelectric thin films, which are in pristine or prepoled single-domain states. In this work, we report reversible in-plane mechanical switching of the monoclinic phase (MC phase) stripe domains in BiFeO3 thin films can be realized by scanning tip force. Via controlling the fast scan direction of the scanning probe microscopy tip and the magnitude of the tip force, the effective trailing field induced by the local tip force can be rotated to consequently switch the net in-plane polarization of the two-variant stripe domain patterns by either 90° or 180°. Moreover, the monoclinic to rhombohedral (MC-R) phase transition occurs during mechanical switching with the distribution of R-phase domains dependent on the switching paths. These results extend our current understanding of the mechanical switching behavior in ferroelectric thin films and should be instructive for their future applications.

5.
ACS Appl Mater Interfaces ; 16(26): 34358-34366, 2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-38913838

RESUMEN

Work function of organometallic halide perovskite (OHP) films is one of the most crucial photoelectric properties, which dominates the carrier dynamics in OHP-based devices. Despite surface treatments by additives being widely used to promote crystallization and passivate defects in OHP films, these chemical strategies for modulation of work functions face two trade-offs: homogeneity on the surface versus along the thickness; the range versus the accuracy of modulation. Herein, by using ferroelectric substrates of uniform polarization and subnanometer roughness, homogeneous CH3NH3PbI3 films are fabricated with five states of work functions with large spanning (∼0.8 eV) and high precision (sd ∼ 0.01 eV). We reveal that the ferroelectric polarizations and the smooth surfaces regulate CH3NH3+ orientations and suppress distortions of PbI6 octahedrons. The wide-range and multistate work functions originate from the ordered CH3NH3+ orientations and PbI6 octahedrons, which result in intensity enhancements and wavelength shifts in photoluminescence with a 30-fold increase of photoexcited carrier lifetime.

6.
Skeletal Radiol ; 2024 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-38877110

RESUMEN

Osteoarthritis (OA) is a leading cause of pain, functional impairment, and disability in older adults. However, there are no effective treatments to delay and reverse OA. Magnetic resonance imaging (MRI) can assess structural abnormalities of OA by directly visualizing damage and inflammatory reactions within the tissues and detecting abnormal signals in the subchondral bone marrow region. While some studies have shown that bone marrow lesions (BMLs) are one of the early signs of the development of OA and predict structural and symptomatic progression of OA, others claimed that BMLs are prevalent in the general population and have no role in the progression of OA. In this narrative review, we screened and summarized studies with different designs that evaluated the association of BMLs with joint symptoms and structural abnormalities of OA. We also discussed whether BMLs may serve as an imaging biomarker and a treatment target for OA based on existing clinical trials.

7.
Heliyon ; 10(10): e30902, 2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38826750

RESUMEN

Background: Radiotherapy has become a standard treatment for chest tumors, but a common complication of radiotherapy is radiation lung injury. Currently, there is still a lack of effective treatment for radiation lung injury. Methods: A mouse model of radioactive lung injury (RILI) was constructed and then treated with different cycles of hydrogen inhalation. Lung function tests were performed to detect changes in lung function.HE staining was used to detect pathological changes in lung tissue. Immunofluorescence staining was used to detect the polarization of macrophages in lung tissue. Immunohistochemistry was used to detect changes in cytokine expression in lung tissues. Western Blot was used to detect the expression of proteins related to the NF-κB signalling pathway. Results: Lung function test results showed that lung function decreased in the model group and improved in the treatment group.HE staining showed that inflammatory response was evident in the model group and decreased in the treatment group. Immunohistochemistry results showed that the expression of pro-inflammatory factors was significantly higher in the model group, and the expression of pro-inflammatory factors was significantly higher in the treatment group. The expression of pro-inflammatory factors in the treatment group was significantly lower than that in the model group, and the expression of anti-inflammatory factors in the treatment group was higher than that in the model group. Immunofluorescence showed that the expression of M1 subtype macrophages was up-regulated in the model group and down-regulated in the treatment group. The expression of M2 subtype macrophages was up-regulated in the treatment group relative to the model group. Western Blot showed that P-NF-κB p65/NF-κB p65 was significantly increased in the model group, and P-NF-κB p65/NF-κB p65 was decreased in the treatment group. Conclusion: Hydrogen therapy promotes macrophage polarization from M1 to M2 subtypes by inhibiting the NF-κB signalling pathway, thereby attenuating the inflammatory response to radiation lung injury.

8.
Insights Imaging ; 15(1): 138, 2024 Jun 09.
Artículo en Inglés | MEDLINE | ID: mdl-38853200

RESUMEN

PURPOSE: To investigate the performance of histogram features of non-Gaussian diffusion metrics for diagnosing muscle invasion and histological grade in bladder cancer (BCa). METHODS: Patients were prospectively allocated to MR scanner1 (training cohort) or MR2 (testing cohort) for conventional diffusion-weighted imaging (DWIconv) and multi-b-value DWI. Metrics of continuous time random walk (CTRW), diffusion kurtosis imaging (DKI), fractional-order calculus (FROC), intravoxel incoherent motion (IVIM), and stretched exponential model (SEM) were simultaneously calculated using multi-b-value DWI. Whole-tumor histogram features were extracted from DWIconv and non-Gaussian diffusion metrics for logistic regression analysis to develop diffusion models diagnosing muscle invasion and histological grade. The models' performances were quantified by area under the receiver operating characteristic curve (AUC). RESULTS: MR1 included 267 pathologically-confirmed BCa patients (median age, 67 years [IQR, 46-82], 222 men) and MR2 included 83 (median age, 65 years [IQR, 31-82], 73 men). For discriminating muscle invasion, CTRW achieved the highest testing AUC of 0.915, higher than DWIconv's 0.805 (p = 0.014), and similar to the combined diffusion model's AUC of 0.885 (p = 0.076). For differentiating histological grade of non-muscle-invasion bladder cancer, IVIM outperformed a testing AUC of 0.897, higher than DWIconv's 0.694 (p = 0.020), and similar to the combined diffusion model's AUC of 0.917 (p = 0.650). In both tasks, DKI, FROC, and SEM failed to show diagnostic superiority over DWIconv (p > 0.05). CONCLUSION: CTRW and IVIM are two potential non-Gaussian diffusion models to improve the MRI application in assessing muscle invasion and histological grade of BCa, respectively. CRITICAL RELEVANCE STATEMENT: Our study validates non-Gaussian diffusion imaging as a reliable, non-invasive technique for early assessment of muscle invasion and histological grade in BCa, enhancing accuracy in diagnosis and improving MRI application in BCa diagnostic procedures. KEY POINTS: Muscular invasion largely determines bladder salvageability in bladder cancer patients. Evaluated non-Gaussian diffusion metrics surpassed DWIconv in BCa muscle invasion and histological grade diagnosis. Non-Gaussian diffusion imaging improved MRI application in preoperative diagnosis of BCa.

9.
Transl Oncol ; 47: 102029, 2024 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-38906066

RESUMEN

Radiation-induced lung injury (RILI) is a severe complication arising from thoracic tumor radiotherapy, which constrains the possibility of increasing radiation dosage. Current RILI therapies provide only limited relief and may result in undesirable side effects. Therefore, there is an urgent demand for effective and low-toxicity treatments for RILI. Macrophages play a pivotal role in RILI, promoting inflammation in the initial stages and facilitating fibrosis in the later stages. Sodium clodronate, a bisphosphonate, can induce macrophage apoptosis when encapsulated in liposomes. In this study, we explored the potential of liposomal sodium clodronate (LC) as a specific agent for depleting macrophages to alleviate acute RILI. We assessed the impact of LC on macrophage consumption both in vitro and in vivo. In a mouse model of acute RILI, LC treatment group led to a reduction in alveolar macrophage counts, mitigated lung injury severity, and lowered levels of pro-inflammatory cytokines in both plasma and bronchoalveolar lavage fluid. Additionally, we further elucidated the specific effects and mechanism of LC on macrophages in vitro. Alveolar macrophages MHS cells were subjected to varying concentrations of LC (0, 50, 100, 200 µg/ml), and the results demonstrated its dose-dependent inhibition of cell proliferation and induction of apoptosis. Moreover, LC decreased the secretion of pro-inflammatory cytokines, including IL-1ß, IL-6, and TNF-α. Conditioned media from LC-treated macrophages protected alveolar epithelial cells MLE-12 from radiation-induced damage, as demonstrated by reduced apoptosis and DNA damage. These findings imply that LC-mediated macrophage depletion may present a promising therapeutic strategy for alleviating radiation-induced lung injury.

10.
Maturitas ; 187: 108057, 2024 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-38908060

RESUMEN

OBJECTIVE: To describe the association of handgrip strength asymmetry and weakness with cognitive function among Chinese middle-aged and older adults. STUDY DESIGN: We used data from four waves (2011, 2013, 2015, and 2018) of the China Health and Retirement Longitudinal Study. Handgrip strength was measured at baseline. Handgrip strength asymmetry was defined on the basis of the ratio of handgrip strength of the non-dominant hand to that of the dominant hand (i.e. non-dominant/dominant): a ratio of <0.9 defined as dominant handgrip strength asymmetry and >1.1 as non-dominant handgrip strength asymmetry. Weakness was defined as a handgrip strength of <28 kg for males or <18 kg for females. MAIN OUTCOME MEASURES: Cognitive function with its two core dimensions (episodic memory and mental status) at each wave was assessed and standardized. RESULTS: 9333 participants (48.3 % female, age 58.2 ± 9.0 years) were included. Non-dominant but not dominant handgrip strength asymmetry was significantly associated with poorer cognitive function at baseline (ß = -0.121, -0.092, and -0.132 for mental status, episodic memory, and global cognition, respectively). In longitudinal analyses over 2 years, dominant handgrip strength asymmetry significantly slowed cognitive decline (ß = -0.078 and -0.069 for mental status and global cognition, respectively), and non-dominant handgrip strength asymmetry accelerated cognitive decline (ß = 0.053 and 0.043 for episodic memory and global cognition, respectively). Weakness was associated with poorer cognitive function at baseline and cognitive decline over 2, 4, and 7 years (all P < 0.05). CONCLUSIONS: In middle-aged and older adults, non-dominant handgrip strength asymmetry and weakness were associated with poorer cognitive function and predicted accelerated cognitive decline. Dominant handgrip strength asymmetry may be beneficial for maintaining cognitive function.

11.
Anal Chem ; 96(25): 10116-10120, 2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-38858219

RESUMEN

In this letter, a sensitive microfluidic immunosensor chip was developed using tetrakis(4-aminophenyl)ethene (TPE)-derived covalent organic frameworks (T-COF) as aggregation-induced electrochemiluminescence (AIECL) emitters and nanobodies as efficient immune recognition units for the detection of thymic stromal lymphopoietin (TSLP), a novel target of asthma. The internal rotation and vibration of TPE molecules were constrained within the framework structure, forcing nonradiative relaxation to convert into pronounced radiative transitions. A camel-derived nanobody exhibited superior specificity, higher residual activity and epitope recognition postcuring compared to monoclonal antibodies. Benefiting from the affinity between silver ions (Ag+) and cytosine (C), a double-stranded DNA (dsDNA) embedded with Ag+ was modified onto the surface of TSLP. A positive correlation was obtained between the TSLP concentration (1.00 pg/mL to 4.00 ng/mL) and ECL intensity, as Ag+ was confirmed to be an excellent accelerator of the generation of free radical species. We propose that utilizing COF to constrain luminescent molecules and trigger the AIECL phenomenon is another promising method for preparing signal tags to detect low-abundance disease-related markers.


Asunto(s)
Citocinas , Técnicas Electroquímicas , Mediciones Luminiscentes , Estilbenos , Linfopoyetina del Estroma Tímico , Citocinas/análisis , Citocinas/metabolismo , Estilbenos/química , Humanos , Estructuras Metalorgánicas/química , Técnicas Biosensibles , Inmunoensayo/métodos , Anticuerpos de Dominio Único/química , Anticuerpos de Dominio Único/inmunología , Técnicas Analíticas Microfluídicas/instrumentación
12.
BMC Med Imaging ; 24(1): 148, 2024 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-38886638

RESUMEN

BACKGROUND: Preoperative discrimination between non-muscle-invasive bladder cancer (NMIBC) and the muscle invasive bladder cancer (MIBC) is a determinant of management. The purpose of this research is to employ radiomics to evaluate the diagnostic value in determining muscle invasiveness of compressed sensing (CS) accelerated 3D T2-weighted-SPACE sequence with high resolution and short acquisition time. METHODS: This prospective study involved 108 participants who underwent preoperative 3D-CS-T2-weighted-SPACE, 3D-T2-weighted-SPACE and T2-weighted sequences. The cohort was divided into training and validation cohorts in a 7:3 ratio. In the training cohort, a Rad-score was constructed based on radiomic features selected by intraclass correlation coefficients, pearson correlation coefficient and least absolute shrinkage and selection operator . Multivariate logistic regression was used to develop a nomogram combined radiomics and clinical indices. In the validation cohort, the performances of the models were evaluated by ROC, calibration, and decision curves. RESULTS: In the validation cohort, the area under ROC curve of 3D-CS-T2-weighted-SPACE, 3D-T2-weighted-SPACE and T2-weighted models were 0.87(95% confidence interval (CI):0.73-1.00), 0.79(95%CI:0.63-0.96) and 0.77(95%CI:0.60-0.93), respectively. The differences in signal-to-noise ratio and contrast-to-noise ratio between 3D-CS-T2-weighted-SPACE and 3D-T2-weighted-SPACE sequences were not statistically significant(p > 0.05). While the clinical model composed of three clinical indices was 0.74(95%CI:0.55-0.94) and the radiomics-clinical nomogram model was 0.88(95%CI:0.75-1.00). The calibration curves confirmed high goodness of fit, and the decision curve also showed that the radiomics model and combined nomogram model yielded higher net benefits than the clinical model. CONCLUSION: The radiomics model based on compressed sensing 3D T2WI sequence, which was acquired within a shorter acquisition time, showed superior diagnostic efficacy in muscle invasion of bladder cancer. Additionally, the nomogram model could enhance the diagnostic performance.


Asunto(s)
Imagenología Tridimensional , Invasividad Neoplásica , Neoplasias de la Vejiga Urinaria , Humanos , Neoplasias de la Vejiga Urinaria/diagnóstico por imagen , Neoplasias de la Vejiga Urinaria/patología , Masculino , Femenino , Persona de Mediana Edad , Invasividad Neoplásica/diagnóstico por imagen , Estudios Prospectivos , Imagenología Tridimensional/métodos , Anciano , Imagen por Resonancia Magnética/métodos , Curva ROC , Nomogramas , Radiómica
13.
Anal Chem ; 96(21): 8390-8398, 2024 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-38716680

RESUMEN

In this work, a microfluidic immunosensor chip was developed by incorporating microfluidic technology with electrochemiluminescence (ECL) for sensitive detection of human epidermal growth factor receptor-2 (HER2). The immunosensor chip can achieve robust reproducibility in mass production by integrating multiple detection units in a series. Notably, nanoscale materials can be better adapted to microfluidic systems, greatly enhancing the accuracy of the immunosensor chip. Ag@Au NCs closed by glutathione (GSH) were introduced in the ECL microfluidic immunosensor system with excellent and stable ECL performance. The synthesized CeO2-Au was applied as a coreaction promoter in the ECL signal amplification system, which made the result of HER2 detection more reliable. In addition, the designed microfluidic immunosensor chip integrated the biosensing system into a microchip, realizing rapid and accurate detection of HER2 by its high throughput and low usage. The developed short peptide ligand NARKFKG (NRK) achieved an effective connection between the antibody and nanocarrier for improving the detection efficiency of the sensor. The immunosensor chip had better storage stability and sensitivity than traditional detection methods, with a wide detection range from 10 fg·mL-1 to 100 ng·mL-1 and a low detection limit (LOD) of 3.29 fg·mL-1. In general, a microfluidic immunosensor platform was successfully constructed, providing a new idea for breast cancer (BC) clinical detection.


Asunto(s)
Técnicas Biosensibles , Técnicas Electroquímicas , Electrodos , Oro , Mediciones Luminiscentes , Nanopartículas del Metal , Receptor ErbB-2 , Plata , Humanos , Receptor ErbB-2/análisis , Receptor ErbB-2/inmunología , Nanopartículas del Metal/química , Técnicas Electroquímicas/métodos , Plata/química , Técnicas Biosensibles/métodos , Oro/química , Inmunoensayo/métodos , Técnicas Analíticas Microfluídicas/instrumentación , Límite de Detección , Cerio/química
14.
Cell ; 187(12): 3024-3038.e14, 2024 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-38781969

RESUMEN

Plants frequently encounter wounding and have evolved an extraordinary regenerative capacity to heal the wounds. However, the wound signal that triggers regenerative responses has not been identified. Here, through characterization of a tomato mutant defective in both wound-induced defense and regeneration, we demonstrate that in tomato, a plant elicitor peptide (Pep), REGENERATION FACTOR1 (REF1), acts as a systemin-independent local wound signal that primarily regulates local defense responses and regenerative responses in response to wounding. We further identified PEPR1/2 ORTHOLOG RECEPTOR-LIKE KINASE1 (PORK1) as the receptor perceiving REF1 signal for plant regeneration. REF1-PORK1-mediated signaling promotes regeneration via activating WOUND-INDUCED DEDIFFERENTIATION 1 (WIND1), a master regulator of wound-induced cellular reprogramming in plants. Thus, REF1-PORK1 signaling represents a conserved phytocytokine pathway to initiate, amplify, and stabilize a signaling cascade that orchestrates wound-triggered organ regeneration. Application of REF1 provides a simple method to boost the regeneration and transformation efficiency of recalcitrant crops.


Asunto(s)
Proteínas de Plantas , Regeneración , Transducción de Señal , Solanum lycopersicum , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Solanum lycopersicum/metabolismo , Regulación de la Expresión Génica de las Plantas , Péptidos/metabolismo
15.
ACS Appl Mater Interfaces ; 16(22): 28029-28040, 2024 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-38775012

RESUMEN

Biophysical and biochemical cues of biomaterials can regulate cell behaviors. Dental pulp stem cells (DPSCs) in pulp tissues can differentiate to odontoblast-like cells and secrete reparative dentin to form a barrier to protect the underlying pulp tissues and enable complete pulp healing. Promotion of the odontogenic differentiation of DPSCs is essential for dentin regeneration. The effects of the surface potentials of biomaterials on the adhesion and odontogenic differentiation of DPSCs remain unclear. Here, poly(vinylidene fluoride-trifluoro ethylene) (P(VDF-TrFE)) films with different surface potentials were prepared by the spin-coating technique and the contact poling method. The cytoskeletal organization of DPSCs grown on P(VDF-TrFE) films was studied by immunofluorescence staining. Using atomic force microscopy (AFM), the lateral detachment forces of DPSCs from P(VDF-TrFE) films were quantified. The effects of electrical stimulation generated from P(VDF-TrFE) films on odontogenic differentiation of DPSCs were evaluated in vitro and in vivo. The unpolarized, positively polarized, and negatively polarized films had surface potentials of -52.9, +902.4, and -502.2 mV, respectively. DPSCs on both negatively and positively polarized P(VDF-TrFE) films had larger cell areas and length-to-width ratios than those on the unpolarized films (P < 0.05). During the detachment of DPSCs from P(VDF-TrFE) films, the average magnitudes of the maximum detachment forces were 29.4, 72.1, and 53.9 nN for unpolarized, positively polarized, and negatively polarized groups, respectively (P < 0.05). The polarized films enhanced the mineralization activities and increased the expression levels of the odontogenic-related proteins of DPSCs compared to the unpolarized films (P < 0.05). The extracellular signal-regulated kinase (ERK) signaling pathway was involved in the odontogenic differentiation of DPSCs as induced by surface charge. In vivo, the polarized P(VDF-TrFE) films enhanced adhesion of DPSCs and promoted the odontogenic differentiation of DPSCs by electrical stimulation, demonstrating a potential application of electroactive biomaterials for reparative dentin formation in direct pulp capping.


Asunto(s)
Adhesión Celular , Diferenciación Celular , Pulpa Dental , Estimulación Eléctrica , Odontogénesis , Polivinilos , Células Madre , Pulpa Dental/citología , Diferenciación Celular/efectos de los fármacos , Células Madre/citología , Células Madre/efectos de los fármacos , Células Madre/metabolismo , Humanos , Adhesión Celular/efectos de los fármacos , Odontogénesis/efectos de los fármacos , Polivinilos/química , Animales , Células Cultivadas , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Propiedades de Superficie
16.
BMC Cancer ; 24(1): 598, 2024 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-38755535

RESUMEN

BACKGROUND: Results regarding whether it is essential to incorporate genetic variants into risk prediction models for esophageal cancer (EC) are inconsistent due to the different genetic backgrounds of the populations studied. We aimed to identify single-nucleotide polymorphisms (SNPs) associated with EC among the Chinese population and to evaluate the performance of genetic and non-genetic factors in a risk model for developing EC. METHODS: A meta-analysis was performed to systematically identify potential SNPs, which were further verified by a case-control study. Three risk models were developed: a genetic model with weighted genetic risk score (wGRS) based on promising SNPs, a non-genetic model with environmental risk factors, and a combined model including both genetic and non-genetic factors. The discrimination ability of the models was compared using the area under the receiver operating characteristic curve (AUC) and the net reclassification index (NRI). The Akaike information criterion (AIC) and Bayesian information criterion (BIC) were used to assess the goodness-of-fit of the models. RESULTS: Five promising SNPs were ultimately utilized to calculate the wGRS. Individuals in the highest quartile of the wGRS had a 4.93-fold (95% confidence interval [CI]: 2.59 to 9.38) increased risk of EC compared with those in the lowest quartile. The genetic or non-genetic model identified EC patients with AUCs ranging from 0.618 to 0.650. The combined model had an AUC of 0.707 (95% CI: 0.669 to 0.743) and was the best-fitting model (AIC = 750.55, BIC = 759.34). The NRI improved when the wGRS was added to the risk model with non-genetic factors only (NRI = 0.082, P = 0.037). CONCLUSIONS: Among the three risk models for EC, the combined model showed optimal predictive performance and can help to identify individuals at risk of EC for tailored preventive measures.


Asunto(s)
Pueblo Asiatico , Neoplasias Esofágicas , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple , Humanos , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/epidemiología , Factores de Riesgo , Estudios de Casos y Controles , China/epidemiología , Pueblo Asiatico/genética , Femenino , Masculino , Persona de Mediana Edad , Medición de Riesgo/métodos , Curva ROC , Interacción Gen-Ambiente , Pueblos del Este de Asia
17.
FASEB J ; 38(8): e23631, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38661062

RESUMEN

Recurrent miscarriage (RM) is related to the dysfunction of extravillous trophoblast cells (EVTs), but the comprehensive mechanisms remain largely unexplored. We analyzed single-cell RNA sequencing (scRNA-seq), bulk RNA sequencing and microarray datasets obtained from Gene Expression Omnibus (GEO) database to explore the hub genes in the mechanisms of RM. We identified 1724 differentially expressed genes (DEGs) in EVTs from the RM, and they were all expressed along the trajectory of EVTs. These DEGs were associated with hypoxia and glucose metabolism. Single-cell Regulatory Network Inference and Clustering (SCENIC) analysis revealed that E2F transcription factor (E2F) 8 (E2F8) was a key transcription factor for these DEGs. And the expression of ENO1 can be positively regulated by E2F8 via RNA sequencing analysis. Subsequently, we performed immunofluorescence assay (IF), plasmid transfection, western blotting, chromatin immunoprecipitation (ChIP), real-time quantitative polymerase chain reaction (qRT-PCR), and transwell assays for validation experiments. We found that the expression of alpha-Enolase 1 (ENO1) was lower in the placentas of RM. Importantly, E2F8 can transcriptionally regulate the expression of ENO1 to promote the invasion of trophoblast cells by inhibiting secreted frizzled-related protein 1/4 (SFRP1/4) to activate Wnt signaling pathway. Our results suggest that ENO1 can promote trophoblast invasion via an E2F8-dependent manner, highlighting a potential novel target for the physiological mechanisms of RM.


Asunto(s)
Aborto Habitual , Proteínas de Unión al ADN , Proteínas Represoras , Trofoblastos , Adulto , Femenino , Humanos , Embarazo , Aborto Habitual/metabolismo , Aborto Habitual/genética , Aborto Habitual/patología , Movimiento Celular , Proteínas de Unión al ADN/metabolismo , Proteínas de Unión al ADN/genética , Fosfopiruvato Hidratasa/metabolismo , Fosfopiruvato Hidratasa/genética , Trofoblastos/metabolismo , Proteínas Supresoras de Tumor/metabolismo , Proteínas Supresoras de Tumor/genética , Proteínas Represoras/metabolismo
18.
Anal Chem ; 96(18): 7265-7273, 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38649306

RESUMEN

The unique optoelectronic and tunable luminescent characteristics of copper nanoclusters (Cu NCs) make them extremely promising as luminophores. However, the limited luminescence intensity and stability of Cu NCs have restricted their application in the field of electrochemiluminescence (ECL). Herein, a self-assembly-induced enhancement strategy was successfully employed to enhance the cathodic ECL performance of flexible ligand-stabilized Cu NCs. Specifically, Cu NCs form ordered sheetlike structures through intermolecular force. The restriction of ligand torsion in this self-assembled structure leads to a significant improvement in the ECL properties of the Cu NCs. Experimental results demonstrate that the assembled nanoscale Cu NC sheets exhibit an approximately three-fold increase in cathodic ECL emission compared to the dispersed state of Cu NCs. Furthermore, assembled nanoscale Cu NCs sheets were utilized as signal probes in conjunction with a specific short peptide derived from the catalytic structural domain of matrix metalloproteinase 14 (MMP 14) as the identification probe, thereby establishing a split-type ECL sensing platform for the quantification of NMP 14. The investigation has revealed the exceptional performance of assembled nanoscale Cu NCs sheets in ECL analysis, thus positioning them as novel and promising signal probes with significant potential in the field of sensing.


Asunto(s)
Cobre , Técnicas Electroquímicas , Mediciones Luminiscentes , Metaloproteinasa 14 de la Matriz , Nanopartículas del Metal , Cobre/química , Técnicas Electroquímicas/métodos , Nanopartículas del Metal/química , Metaloproteinasa 14 de la Matriz/metabolismo , Metaloproteinasa 14 de la Matriz/análisis , Electrodos , Humanos
19.
Aging (Albany NY) ; 16(8): 7426-7436, 2024 04 25.
Artículo en Inglés | MEDLINE | ID: mdl-38663941

RESUMEN

Head and neck tumors are malignant tumors that appear in the head and neck. Although much progress has been made in the treatment of head and neck tumors, many challenges remain. The prognosis of some advanced cases remains poor and survival and quality of life after treatment face certain limitations. Therefore, further research into the pathogenesis and treatment options for head and neck tumors is important in order to improve the prognosis and quality of life of patients. The Protein Arginine Methyltransferase (PRMT) family is a class of enzymes that are responsible for adding methyl groups to arginine residues in proteins. PRMT family members play important roles in regulating many cellular processes, such as transcriptional regulation, signaling, and cell cycle regulation. Recent studies have shown that the PRMT family also plays an important function in tumorigenesis and development. Here, we found that PRMT family members are significantly overexpressed in head and neck tumors and that PRMT5 may serve as an independent prognostic factor in head and neck tumors. We found that PRMT5-regulated differential genes were significantly enriched in tumor-associated signaling pathways such as IL-17 and p53. And we also found that the expression of PRMT5 in head and neck tumors was significantly correlated with immune cell infiltration, m6A as well as the expression of ferroptosis-related genes, and drug sensitivity. These results suggest that PRMT may play an important role in the development of head and neck tumors.


Asunto(s)
Ferroptosis , Neoplasias de Cabeza y Cuello , Proteína-Arginina N-Metiltransferasas , Carcinoma de Células Escamosas de Cabeza y Cuello , Humanos , Proteína-Arginina N-Metiltransferasas/genética , Proteína-Arginina N-Metiltransferasas/metabolismo , Ferroptosis/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/inmunología , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Neoplasias de Cabeza y Cuello/genética , Neoplasias de Cabeza y Cuello/inmunología , Neoplasias de Cabeza y Cuello/patología , Regulación Neoplásica de la Expresión Génica , Masculino , Femenino , Pronóstico , Persona de Mediana Edad , Transducción de Señal
20.
Nat Commun ; 15(1): 2815, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38561357

RESUMEN

Reversible solid-state hydrogen storage of magnesium hydride, traditionally driven by external heating, is constrained by massive energy input and low systematic energy density. Herein, a single phase of Mg2Ni(Cu) alloy is designed via atomic reconstruction to achieve the ideal integration of photothermal and catalytic effects for stable solar-driven hydrogen storage of MgH2. With the intra/inter-band transitions of Mg2Ni(Cu) and its hydrogenated state, over 85% absorption in the entire spectrum is achieved, resulting in the temperature up to 261.8 °C under 2.6 W cm-2. Moreover, the hydrogen storage reaction of Mg2Ni(Cu) is thermodynamically and kinetically favored, and the imbalanced distribution of the light-induced hot electrons within CuNi and Mg2Ni(Cu) facilitates the weakening of Mg-H bonds of MgH2, enhancing the "hydrogen pump" effect of Mg2Ni(Cu)/Mg2Ni(Cu)H4. The reversible generation of Mg2Ni(Cu) upon repeated dehydrogenation process enables the continuous integration of photothermal and catalytic roles stably, ensuring the direct action of localized heat on the catalytic sites without any heat loss, thereby achieving a 6.1 wt.% H2 reversible capacity with 95% retention under 3.5 W cm-2.

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