RESUMEN
The Hedgehog (Hh) signaling pathway orchestrates its influence through a dynamic interplay of Hh proteins, the cell surface receptor Ptch1, Smo, and Gli transcription factors, contributing to a myriad of developmental events. Indian Hedgehog (Ihh) and Gli zinc finger transcription factor 1 (Gli1) play crucial roles in developmental regulation within the Hh signaling pathway. Ihh regulates chondrocyte proliferation, differentiation, and bone formation, impacting the development of cranial bones, cartilage, and the temporomandibular joint (TMJ). Losing Ihh results in cranial bone malformation and decreased ossification and affects the formation of cranial base cartilage unions, TMJ condyles, and joint discs. Gli1 is predominantly expressed during early craniofacial development, and Gli1+ cells are identified as the primary mesenchymal stem cells (MSCs) for craniofacial bones, crucial for cell differentiation and morphogenesis. In addition, a complex mutual regulatory mechanism exists between Gli1 and Ihh, ensuring the normal function of the Hh signaling pathway by directly or indirectly regulating each other's expression levels. And the interaction between Ihh and Gli1 significantly impacts the normal development of craniofacial tissues. This review summarizes the pivotal roles of Gli1 and Ihh in the intricate landscape of mammalian craniofacial development and outlines the molecular regulatory mechanisms and intricate interactions governing the growth of bone and cartilage exhibited by Gli1 and Ihh, which provides new insights into potential therapeutic strategies for related diseases or researches of tissue regeneration.
Asunto(s)
Proteínas Hedgehog , Transducción de Señal , Proteína con Dedos de Zinc GLI1 , Proteína con Dedos de Zinc GLI1/metabolismo , Proteína con Dedos de Zinc GLI1/genética , Humanos , Proteínas Hedgehog/metabolismo , Proteínas Hedgehog/genética , Animales , Cráneo/metabolismo , Cráneo/embriología , Cráneo/crecimiento & desarrollo , Diferenciación Celular , Regulación del Desarrollo de la Expresión GénicaRESUMEN
Synergetic treatments that combine chemotherapy with photothermal/photodynamic therapy have been developed as promising new strategies for cancer therapy, especially for drug-resistant cancers. To achieve optimized synergetic outcomes for cancer therapy, it is highly desirable to selectively and simultaneously deliver both chemotherapeutics and near-infrared photosensitizers to the cancer tissues and cells, enhancing local accumulation. Here we report the preparation of poly-ε-caprolactone nanoparticles (PCL NPs) using bovine albumin as a stabilizer; the nanoparticles are loaded with IR780 and paclitaxel (PTX) for combinational phototherapy and chemotherapy. Moreover, in order to enable active targeting toward ovarian cancer, a specific peptide recognizing luteinizing hormone-releasing hormone receptors (LHRH) on ovarian cancer cells was covalently grafted onto the surface of the as-prepared NPs. As a result, LHRH peptide modified PCL (PCL-LHRH) NPs demonstrated increased internalization in ovarian tumor cells in vitro and selective targeting in tumor xenografts in vivo. PTX and IR780 can be efficiently encapsulated into PCL-LHRH NPs by an oil-in-water emulsion and solvent evaporation method. The systematic administration of ovarian tumor targeting PCL-LHRH/IR780-PTX can efficiently hinder the growth of drug-resistant xenografts in vivo with the assistance of an 808 nm near-infrared laser. These findings indicate that peptide mediated tumor targeting multifunctional nanomaterials may have remarkable profits in controlled drug delivery and synergistic therapy on drug-resistant cancer.