RESUMEN
Alum-crosslinked hyaluronic acid-dopamine (HD) hydrogel containing indocyanine green (ICG) with anti-programmed cell death-1 (PD-1) antibody (Ab) administration was developed for immunophoto therapy of cancer. Alum modulates the rheological characteristics of hydrogel for enabling syringe injection, shear-thinning feature, and slower biodegradation. In addition, alum in HD-based hydrogel provided CD8+ T cell-mediated immune responses for cancer therapy. ICG in the hydrogel under near-infrared (NIR) light exposure may induce hyperthermia and generate singlet oxygen for selective cancer cell killing. HD/alum/ICG hydrogel injection with NIR laser irradiation elevated PD-1 level in CD8+ T cells. Administration of PD-1 Ab aiming at highly expressed PD-1 in T cells may amplify the anticancer efficacies of HD/alum/ICG hydrogel along with NIR laser. HD/alum/ICG hydrogel with NIR light may have both CD8+ T cell-linked immune responses and ICG-related photodynamic/photothermal effects. Additional injection of immune checkpoint inhibitor can ultimately suppress primary and distant tumor growth by combination with those therapeutic actions.
RESUMEN
Programmed cell death protein 1 (PD-1), expressed on tumor-infiltrating T cells, is a T cell exhaustion marker. The mechanisms underlying PD-1 upregulation in CD4 T cells remain unknown. Here we develop nutrient-deprived media and a conditional knockout female mouse model to study the mechanism underlying PD-1 upregulation. Reduced methionine increases PD-1 expression on CD4 T cells. The genetic ablation of SLC43A2 in cancer cells restores methionine metabolism in CD4 T cells, increasing the intracellular levels of S-adenosylmethionine and yielding H3K79me2. Reduced H3K79me2 due to methionine deprivation downregulates AMPK, upregulates PD-1 expression and impairs antitumor immunity in CD4 T cells. Methionine supplementation restores H3K79 methylation and AMPK expression, lowering PD-1 levels. AMPK-deficient CD4 T cells exhibit increased endoplasmic reticulum stress and Xbp1s transcript levels. Our results demonstrate that AMPK is a methionine-dependent regulator of the epigenetic control of PD-1 expression in CD4 T cells, a metabolic checkpoint for CD4 T cell exhaustion.
Asunto(s)
Linfocitos T CD4-Positivos , Neoplasias , Receptor de Muerte Celular Programada 1 , Animales , Femenino , Ratones , Proteínas Quinasas Activadas por AMP/metabolismo , Linfocitos T CD8-positivos , Metionina/metabolismo , Ratones Noqueados , Neoplasias/metabolismo , Receptor de Muerte Celular Programada 1/metabolismo , Racemetionina/metabolismo , Regulación hacia ArribaRESUMEN
Current medical school education focuses on acquiring appropriate knowledge with relatively little interest in developing the career selection skills of medical students. We investigated medical students' perceptions of career problems and the required types of career counseling programs. Five focus group discussions were held with 23 medical students. The consensual qualitative study method was used to analyze the recorded discussion process. The medical students were more influenced by parents and grades than by subjective choices when deciding on admission to medical school. In future career choices, medical students considered the stability and feasibility of the career and expected quality of life. However, there were several opinions that it is essential to understand oneself. Objective and specific career information was lacking, and meeting with the professor was not very helpful for career counseling. Most medical students expected the effectiveness of the career counseling program but hoped the program would proceed with voluntary participation. Medical students wanted a variety of concrete and objective information, such as specialty information for choosing residency training, trainee hospital information, and post-residency training information in the career counseling program. Most medical students are not ready for career-related problems, therefore making it necessary to develop a career counseling program suitable for them.
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Estudiantes de Medicina , Orientación Vocacional , Selección de Profesión , Humanos , Calidad de Vida , República de CoreaRESUMEN
This study aims to demonstrate a comprehensive understanding of the life experience of victims of medical accidents after medical accidents and medical litigations. A single victim of a medical accident participated in the study. Six upper categories were derived as the results: "frustration and anger toward medical accident occurrence," "desolated struggle for medical litigation," "distrust of medical litigation related legal profession," "accepting myself with a disability caused by a medical accident," "a life with far more unexpected challenges as an athlete with disabilities," and "find new meaning after the medical accident." The participant was experiencing physical and psychological distress in the process of accepting the medical accident and the disability. In addition, the participant was exposed to the secondary psychological distress from the medical profession, lawyer, and legal profession in the peculiar situation of medical litigation, and to the third psychological distress in life living as a disabled person.
Asunto(s)
Accidentes , Actitud , Personas con Discapacidad/psicología , Jurisprudencia , Errores Médicos/psicología , Estrés Psicológico , Adaptación Psicológica , Adulto , Atletas , Emociones , Femenino , Humanos , Abogados , Acontecimientos que Cambian la Vida , Investigación CualitativaRESUMEN
Our research revealed differences in work-family constructs for employed mothers in 3 countries, Israel (N = 105), Korea (N = 298), and the United States (N = 305). Although levels of work-family conflict were comparable, the Korean women had the lowest levels of work-family enrichment compared with the Israeli and American mothers. Moreover, Korean women reported the most depression and the least support from both spouses and employers. Spousal support mediated the relationship between work-family conflict and depression for employed mothers in Israel, Korea, and the United States. As hypothesized by conservation of resources theory (Hobfoll, 1989, 1998, 2001), threat of resource loss (operationalized as work-family conflict) was related to depression more strongly than was resource gain (i.e., work-family enrichment).