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1.
J Biol Chem ; 299(9): 105127, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37544647

RESUMEN

Diabetic keratopathy, commonly associated with a hyperactive inflammatory response, is one of the most common eye complications of diabetes. The peptide hormone fibroblast growth factor-21 (FGF-21) has been demonstrated to have anti-inflammatory and antioxidant properties. However, whether administration of recombinant human (rh) FGF-21 can potentially regulate diabetic keratopathy is still unknown. Therefore, in this work, we investigated the role of rhFGF-21 in the modulation of corneal epithelial wound healing, the inflammation response, and oxidative stress using type 1 diabetic mice and high glucose-treated human corneal epithelial cells. Our experimental results indicated that the application of rhFGF-21 contributed to the enhancement of epithelial wound healing. This treatment also led to advancements in tear production and reduction in corneal edema. Moreover, there was a notable reduction in the levels of proinflammatory cytokines such as TNF-α, IL-6, IL-1ß, MCP-1, IFN-γ, MMP-2, and MMP-9 in both diabetic mouse corneal epithelium and human corneal epithelial cells treated with high glucose. Furthermore, we found rhFGF-21 treatment inhibited reactive oxygen species production and increased levels of anti-inflammatory molecules IL-10 and SOD-1, which suggests that FGF-21 has a protective role in diabetic corneal epithelial healing by increasing the antioxidant capacity and reducing the release of inflammatory mediators and matrix metalloproteinases. Therefore, we propose that administration of FGF-21 may represent a potential treatment for diabetic keratopathy.


Asunto(s)
Enfermedades de la Córnea , Complicaciones de la Diabetes , Diabetes Mellitus Experimental , Epitelio Corneal , Factores de Crecimiento de Fibroblastos , Mediadores de Inflamación , Estrés Oxidativo , Cicatrización de Heridas , Animales , Humanos , Ratones , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Enfermedades de la Córnea/complicaciones , Enfermedades de la Córnea/tratamiento farmacológico , Enfermedades de la Córnea/metabolismo , Complicaciones de la Diabetes/tratamiento farmacológico , Complicaciones de la Diabetes/metabolismo , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/metabolismo , Epitelio Corneal/efectos de los fármacos , Factores de Crecimiento de Fibroblastos/farmacología , Factores de Crecimiento de Fibroblastos/uso terapéutico , Glucosa/efectos adversos , Glucosa/metabolismo , Mediadores de Inflamación/metabolismo , Metaloproteinasas de la Matriz/metabolismo , Estrés Oxidativo/efectos de los fármacos , Cicatrización de Heridas/efectos de los fármacos
2.
Sensors (Basel) ; 24(18)2024 Sep 21.
Artículo en Inglés | MEDLINE | ID: mdl-39338851

RESUMEN

The leaf area index (LAI) is a key indicator of vegetation canopy structure and growth status, crucial for global ecological environment research. The Moderate Resolution Spectral Imager-II (MERSI-II) aboard Fengyun-3D (FY-3D) covers the globe twice daily, providing a reliable data source for large-scale and high-frequency LAI estimation. VI-based LAI estimation is effective, but species and growth status impacts on the sensitivity of the VI-LAI relationship are rarely considered, especially for MERSI-II. This study analyzed the VI-LAI relationship for eight biomes in China with contrasting leaf structures and canopy architectures. The LAI was estimated by adaptively combining multiple VIs and validated using MODIS, GLASS, and ground measurements. Results show that (1) species and growth stages significantly affect VI-LAI sensitivity. For example, the EVI is optimal for broadleaf crops in winter, while the RDVI is best for evergreen needleleaf forests in summer. (2) Combining vegetation indices can significantly optimize sensitivity. The accuracy of multi-VI-based LAI retrieval is notably higher than using a single VI for the entire year. (3) MERSI-II shows good spatial-temporal consistency with MODIS and GLASS and is more sensitive to vegetation growth fluctuation. Direct validation with ground-truth data also demonstrates that the uncertainty of retrievals is acceptable (R2 = 0.808, RMSE = 0.642).


Asunto(s)
Hojas de la Planta , Hojas de la Planta/crecimiento & desarrollo , China , Ecosistema , Bosques , Imágenes Satelitales/métodos , Estaciones del Año
3.
Appl Biochem Biotechnol ; 196(1): 573-587, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37160564

RESUMEN

Molecular-targeted therapies for lung squamous cell carcinoma (LSCC) are limited mainly because targetable oncogenic aberrations are absent in LSCC. Recent genomic analyses have revealed that the fibroblast growth factor (FGF) signaling pathway plays a fundamental role in LSCC progression via cancer cell proliferation and angiogenesis. In the present study, we designed, expressed, and purified a fibroblast growth factor receptor fragment (FGFR1-Fc) fusion protein using NS/0 cells. In FGF2-FGFR1 overexpressed NCI-H1703 cells, the FGFR1-Fc fusion protein effectively inhibited proliferation and invasion and arrested the cell cycle at the G0-G1 phase. In NCI-H1703 cells treated with the FGFR1-Fc fusion protein, the phosphorylation levels of FGFR1, FRS2, ERK, and AKT were significantly reduced. Using an siRNA assay, we demonstrated that FGF2-FGFR1 is the major anti-tumor target of FGFR1-Fc fusion the FGFR1-Fc fusion protein, which also significantly inhibited proliferation and invasion by NCI-H1703 cells via the FGF2-FGFR1 signaling pathway. In addition, the FGFR1-Fc fusion protein significantly inhibited angiogenesis in an embryonic chorioallantoic membrane model. The FGFR1-Fc fusion protein may be an effective therapeutic candidate for LSCC.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Carcinoma de Células Escamosas , Inmunoglobulina G , Neoplasias Pulmonares , Proteínas Recombinantes de Fusión , Humanos , Factor 2 de Crecimiento de Fibroblastos , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos/genética , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos/metabolismo , Proliferación Celular , Carcinoma de Células Escamosas/genética , Neoplasias Pulmonares/tratamiento farmacológico , Pulmón/metabolismo , Línea Celular Tumoral
4.
JACS Au ; 4(9): 3690-3704, 2024 Sep 23.
Artículo en Inglés | MEDLINE | ID: mdl-39328748

RESUMEN

Biomolecular condensation involving proteins and nucleic acids has been recognized to play crucial roles in genome organization and transcriptional regulation. However, the biophysical mechanisms underlying the droplet fusion dynamics and microstructure evolution during the early stage of liquid-liquid phase separation (LLPS) remain elusive. In this work, we study the phase separation of linker histone H1, which is among the most abundant chromatin proteins, in the presence of single-stranded DNA (ssDNA) capable of forming a G-quadruplex by using molecular simulations and experimental characterization. We found that droplet fusion is a rather stochastic and kinetically controlled process. Productive fusion events are triggered by the formation of ssDNA-mediated electrostatic bridges within the droplet contacting zone. The droplet microstructure is size-dependent and evolves driven by maximizing the number of electrostatic contacts. We also showed that the folding of ssDNA to the G-quadruplex promotes LLPS by increasing the multivalency and strength of protein-DNA interactions. These findings provide deep mechanistic insights into the growth dynamics of biomolecular droplets and highlight the key role of kinetic control during the early stage of ssDNA-protein condensation.

5.
Medicine (Baltimore) ; 102(38): e35062, 2023 Sep 22.
Artículo en Inglés | MEDLINE | ID: mdl-37747015

RESUMEN

BACKGROUND: To evaluate through meta-analysis whether long-term use of proton pump inhibitor (PPI) increases the risk of precancerous lesions in the stomach. METHODS: Randomized controlled trials that compared the occurrence and progression of precancerous lesions in patients receiving PPI treatment versus non-PPI treatment were retrieved from CNKI, VIP, Wanfang, CBM, Pubmed, Embase, Web of Science, and Cochrane Library databases (from database inception to May 1, 2023). The Revman 5.3 and STATA 17.0 software were used for analysis, and subgroup analysis was conducted based on follow-up time (≤12 months and > 12 months) and lesion type (atrophic gastritis, intestinal metaplasia, and epithelial dysplasia). RESULTS: Six randomized controlled trials with a total of 1623 cases were included, including 1015 cases in the experimental group and 608 cases in the control group. The meta-analysis results showed that the overall abnormal lesion rate combined with statistical relative risk (RR) = 1.31 (0.85-2.02), P = .23. Subgroup analysis showed that the follow-up time > 12 months combined result was RR = 2.21 (1.47-3.33), P = .0001, the intestinal metaplasia group combined result was RR = 1.96 (0.91-2.47), P = .04. CONCLUSION SUBSECTIONS: During long-term follow-up, patients using PPI exhibited a significantly higher incidence of overall abnormal lesions compared to the control group, particularly with a higher risk observed for intestinal metaplasia. However, there were no statistically significant differences between the 2 groups in terms of short-term follow-up and other types of lesions. It is important to exercise caution when interpreting these findings due to the limited number of nominated investigations included in the meta-analysis.


Asunto(s)
Carcinoma in Situ , Lesiones Precancerosas , Humanos , Inhibidores de la Bomba de Protones/efectos adversos , Ensayos Clínicos Controlados Aleatorios como Asunto , Estómago , Lesiones Precancerosas/inducido químicamente , Lesiones Precancerosas/epidemiología
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