RESUMEN
Extruded three-dimensional (3D) printing based on photocurable materials has shown good application prospects in the medical field. This has been attributed to the operational aspect that can be performed at room temperature and the high mechanical strength of the extrudate and final product. However, the commonly used photocurable polymer, polyethylene glycol diacrylate (PEGDA), has a low viscosity and exhibits a long crosslinking time. Therefore, additives are added to improve the printability of the extrudate. In this study, various hydrogels were used to improve the mixing uniformity and rheological behavior of PEGDA-based printing materials. Printing accuracy and mechanical strength were evaluated to optimize print material composition and process parameters. Hydroxypropyl methylcellulose K100M was found to improve the shear thinning and self-supporting properties of printing materials, which were essential for printability. Although the storage modulus of the photocured material proportionally increased with curing time in the range of 20-80 s, the minimal layer time of the 3D samples remained at 65 s, ensuring interlayer adhesion. Gastro-floating tablets with different infill densities were printed to illustrate the application of 3D extrusion printing in personalized medicine. The weight, crushing strength, and floating time were regulated by the infill density of the models. Overall, this study demonstrates that extrusion printing with a photocurable material is an easy way to prepare customized oral preparations with complex internal structures and tunable properties.
Asunto(s)
Polietilenglicoles , Impresión Tridimensional , Derivados de la Hipromelosa , Estómago , ComprimidosRESUMEN
Multiple endocrine neoplasia type 2 (MEN2) is a neuroendocrine cancer syndrome characterized by medullary thyroid carcinoma, in combination or not with pheochromocytoma, hyperparathyroidism, and extra-endocrine features. MEN2 syndrome includes two clinically distinct forms subtyped as MEN2A and MEN2B. Nearly all MEN2 cases are caused by germline mutations of the RET proto-oncogene. In this review, we propose "5P" strategies for management of MEN2: prevention, prediction, personalization, psychological support, and participation, which could effectively improve clinical outcomes of patients. Based on RET mutations, MEN2 could be prevented through prenatal diagnosis or preimplantation genetic testing. Identification of pathogenic mutations in RET can enable early diagnosis of MEN2. Combining RET mutation testing with measurement of serum calcitonin, plasma or urinary metanephrine/normetanephrine, and serum parathyroid hormone levels could allow risk stratification and accurately prediction of MEN2 progression, thus facilitating implementation of personalized precision treatments to increase disease-free survival and overall survival. Furthermore, increased awareness of MEN2 is needed, which requires participation of physicians, patients, family members, and related organizations. Psychological support is also important for patients with MEN2 to promote comprehensive management of MEN2 symptoms. The "5P" strategies for management of MEN2 represent a typical clinical example of precision medicine. These strategies could effectively improve the health of MEN2 patient, and avoid adverse outcomes, including death and major morbidity, from MEN2.
Asunto(s)
Neoplasia Endocrina Múltiple Tipo 2a/terapia , Medicina de Precisión/métodos , Manejo de la Enfermedad , Pruebas Genéticas , Humanos , Neoplasia Endocrina Múltiple Tipo 2a/diagnóstico , Neoplasia Endocrina Múltiple Tipo 2a/genética , Proto-Oncogenes Mas , Proteínas Proto-Oncogénicas c-ret/genéticaRESUMEN
In the present study, we investigate the effect of reduced cystathionine-γ-lyase (CSE) expression in high glucose induced metalloproteinases14 (MMP14) expression in adipocytes and visceral adipose tissues. Diabetic mice were prepared by injections of STZ and the expression of CSE, MMP14 in visceral adipose tissues were determined. Adipocytes were differentiated from 3T3-L1 cells and treated with high glucose (HG), H2S slow-releasing compound GYY4137 or transfected with CSE siRNA. Then the expression of CSE, MMP14 were determined by western blotting. CSE knockout mice were generated by crossing CSE+/- heterozygous mice and given intraperitoneally (i.p.) injections of GYY4137, and then the expression of CSE and MMP14 in visceral adipose tissues were determined by quantitative real-time PCR and western blotting. The following results were obtained from the study. In adipose tissues of diabetic mice, the mRNA and protein expression of MMP14 increased while the mRNA and protein expression of CSE decreased. In 3T3-L1 adipocytes, both HG DMEM and CSE siRNA transfection increased the mRNA and protein of MMP14. The addition of GYY4137 inhibited HG-induced upregulation of MMP14 expression. In CSE knockout mice, the mRNA and protein expression of MMP14 in adipose tissues increased, which could be inhibited by i.p. injections of GYY4137. In conclusion, high glucose increased the expression of MMP14 in adipocytes and visceral adipose tissues through inhibiting the expression of CSE.