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1.
Tumour Biol ; 37(9): 11753-11762, 2016 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-27022736

RESUMEN

Interleukin-22 (IL-22) is an inflammatory cytokine mainly produced by activated Th17 and Th22 cells. The data presented here demonstrate that IL-22 induced the migration and invasion of papillary thyroid cancer (PTC) cells. MicroRNA expression analysis and functional studies indicated that IL-22-mediated migration and invasion is positively regulated by miR-595. Further mechanistic studies revealed that sex-determining region Y-box 17 (Sox17) is directly targeted by miR-595. We then demonstrated that IL-22 regulated migration and invasion of PTC cells via inhibiting Sox17 expression. Interestingly, in PTC cell lines and PTC tissues, expression of IL-22 and miR-595 was upregulated and Sox17 downregulated compared with normal thyroid, and their expression levels were closely correlated. Taken together, this present study suggests that IL-22 stimulation enhances the migration and invasion of PTC cells by regulating miR-595 and its target Sox17.


Asunto(s)
Carcinoma/patología , Interleucinas/farmacología , MicroARNs/fisiología , Factores de Transcripción SOXF/fisiología , Neoplasias de la Tiroides/patología , Carcinoma Papilar , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Humanos , Invasividad Neoplásica , Factores de Transcripción SOXF/genética , Cáncer Papilar Tiroideo , Interleucina-22
2.
Acta Chim Slov ; 71(3): 509-518, 2024 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-39324322

RESUMEN

The biosynthesis of fatty acids constitutes a critical metabolic pathway in bacterial organisms. Prior investigations have highlighted the synthesis of antimicrobial compounds anchored in the benzodioxepin scaffold, noted for their pronounced antibacterial properties. Leveraging this foundational knowledge, the current research endeavors to meticulously engineer and synthesize a series of eight innovative benzodioxepin amide-biphenyl derivatives. This achievement was realized through the sophisticated optimization of synthetic methodologies. The scope of this study extends to a rigorous evaluation of the antibacterial prowess and biocompatibility of the aforementioned novel derivatives. Notably, Compound E4 emerged as a supremely potent antimicrobial agent. A detailed elucidation of the crystalline architecture of Compound E4 was conducted, alongside a thorough docking study to explore its interactions with the FabH enzyme.


Asunto(s)
Amidas , Antibacterianos , Compuestos de Bifenilo , Pruebas de Sensibilidad Microbiana , Antibacterianos/farmacología , Antibacterianos/síntesis química , Antibacterianos/química , Amidas/farmacología , Amidas/química , Amidas/síntesis química , Compuestos de Bifenilo/química , Simulación del Acoplamiento Molecular , Benzodioxoles/farmacología , Benzodioxoles/síntesis química , Benzodioxoles/química , Relación Estructura-Actividad , Staphylococcus aureus/efectos de los fármacos , Estructura Molecular
3.
Eur J Med Chem ; 265: 116064, 2024 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-38159483

RESUMEN

The enzyme FabH plays a critical role in the initial step of fatty acid biosynthesis, which is vital for the survival of bacteria. As a result, FabH has emerged as an appealing target for the development of novel antibacterial agents. In this study, employing the chemical proteomics method, we validated the previously identified skeleton amide derivatives bearing dioxygenated rings, potentially formed through metabolic processes. Building upon the proteomics findings, we then synthesized and evaluated 32 compounds containing N-heterocyclic amides for their antimicrobial activity for future optimizing the deoxygenated amides. Several compounds demonstrated potent antimicrobial properties with low toxicity, particularly compound 25, which exhibited remarkable potential as an agent with an MIC range of 1.25-3.13 µg/mL against the tested bacterial strains and an IC50 of 2.0 µM against E. coli-derived FabH. Furthermore, we evaluated nine analogues with relatively low MIC values through cytotoxicity and hemolytic activity assessments, Lipinski's rule-of-five criteria, and in silico ADMET predictions to ascertain their druggability potential. Notably, a detailed docking simulation was performed to investigate the binding interactions of compound 25 within the binding pocket of E. coli FabH, which encouragingly revealed strong binding interactions. Based on our findings, compound 25 emerges as the optimal candidate for in vivo therapy aimed at treating infected skin defects. Remarkably, the application of compound 25 demonstrated a significant reduction in the duration of wound infection and notably accelerated the healing process of infected wounds, achieving an impressive 94 % healing rate by day 10.


Asunto(s)
Antibacterianos , Proteínas de Escherichia coli , Antibacterianos/farmacología , Antibacterianos/química , Escherichia coli , Bacterias , Simulación del Acoplamiento Molecular , Pruebas de Sensibilidad Microbiana , Relación Estructura-Actividad
4.
Adv Sci (Weinh) ; 11(33): e2401869, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38959395

RESUMEN

Ionic conductive hydrogels (ICHs) have recently gained prominence in biosensing, indicating their potential to redefine future biomedical applications. However, the integration of these hydrogels into sensor technologies and their long-term efficacy in practical applications pose substantial challenges, including a synergy of features, such as mechanical adaptability, conductive sensitivity, self-adhesion, self-regeneration, and microbial resistance. To address these challenges, this study introduces a novel hydrogel system using an imidazolium salt with a ureido backbone (UL) as the primary monomer. Fabricated via a straightforward one-pot copolymerization process that includes betaine sulfonate methacrylate (SBMA) and acrylamide (AM), the hydrogel demonstrates multifunctional properties. The innovation of this hydrogel is attributed to its robust mechanical attributes, outstanding strain responsiveness, effective water retention, and advanced self-regenerative and healing capabilities, which collectively lead to its superior performance in various applications. Moreover, this hydrogel  exhibited broad-spectrum antibacterial activity. Its potential for biomechanical monitoring, especially in tandem with contact and noncontact electrocardiogram (ECG) devices, represents a noteworthy advancement in precise real-time cardiac monitoring in clinical environments. In addition, the conductive properties of the hydrogel make it an ideal substrate for electrophoretic patches aimed at treating infected wounds and consequently enhancing the healing process.


Asunto(s)
Técnicas Biosensibles , Hidrogeles , Líquidos Iónicos , Hidrogeles/química , Técnicas Biosensibles/métodos , Líquidos Iónicos/química , Conductividad Eléctrica , Antibacterianos/farmacología
5.
Artículo en Inglés | MEDLINE | ID: mdl-32998298

RESUMEN

PURPOSE: The current study aims to explore the barriers for middle-aged Chinese to learn about and uptake low-dose computed tomography (LDCT) lung cancer screening. METHODS: Data were collected via an online survey in December 2019. Final valid sample included 640 respondents, aged 40-60 years old, from 21 provinces of China. We performed multiple linear regressions to test the potential barriers to LDCT scan. FINDINGS: Cost concerns, distrust in doctors, fears of disease, lack of knowledge, and optimistic bias are negatively associated with the intention to learn about and uptake LDCT scan. IMPLICATIONS: Our study contributes to understanding the negative predictors of middle-aged Chinese to get LDCT lung cancer scans. Future campaign programs should help audiences to build comprehensive understandings about lung cancer and LDCT scan. To better promote LDCT scan in China, the government should fund more trial programs continuously and public efforts should be made to rebuild the patient-doctor trust.


Asunto(s)
Detección Precoz del Cáncer , Neoplasias Pulmonares/diagnóstico por imagen , Adulto , Anciano , Pueblo Asiatico , China , Humanos , Tamizaje Masivo , Persona de Mediana Edad , Tomografía Computarizada por Rayos X
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