RESUMEN
Glioblastoma (GBM) is the most aggressive malignant primary brain tumor characterized by a highly heterogeneous and immunosuppressive tumor microenvironment (TME). The symbiotic interactions between glioblastoma stem cells (GSCs) and tumor-associated macrophages (TAM) in the TME are critical for tumor progression. Here, we identified that IFI35, a transcriptional regulatory factor, plays both cell-intrinsic and cell-extrinsic roles in maintaining GSCs and the immunosuppressive TME. IFI35 induced non-canonical NF-kB signaling through proteasomal processing of p105 to the DNA-binding transcription factor p50, which heterodimerizes with RELB (RELB/p50), and activated cell chemotaxis in a cell-autonomous manner. Further, IFI35 induced recruitment and maintenance of M2-like TAMs in TME in a paracrine manner. Targeting IFI35 effectively suppressed in vivo tumor growth and prolonged survival of orthotopic xenograft-bearing mice. Collectively, these findings reveal the tumor-promoting functions of IFI35 and suggest that targeting IFI35 or its downstream effectors may provide effective approaches to improve GBM treatment.
Asunto(s)
Glioblastoma , FN-kappa B , Células Madre Neoplásicas , Transducción de Señal , Macrófagos Asociados a Tumores , Glioblastoma/metabolismo , Glioblastoma/patología , Glioblastoma/genética , Humanos , Animales , Ratones , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patología , Macrófagos Asociados a Tumores/metabolismo , Macrófagos Asociados a Tumores/patología , FN-kappa B/metabolismo , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/genética , Línea Celular Tumoral , Microambiente TumoralRESUMEN
BACKGROUND: The burden of elderly cardiovascular disease (CVD) has received increasing attention with population ageing worldwide. AIMS: We reported on the global CVD burden in elderly individuals over 70, 1990-2019. METHODS AND RESULTS: Based on the Global Burden of Disease Study 2019, elderly CVD burden data were analysed. Temporal burden trends were analysed with the joinpoint model. The slope index and concentration index were used to evaluate health inequality. From 1990 to 2019, the global elderly CVD incidence, prevalence, death, and disability-adjusted life year rates generally decreased. However, the current burden remains high. The rapid growth in burden in parts of sub-Saharan Africa and Asia is a cause for concern. Countries with a higher socio-demographic index (SDI) have generally seen a greater decrease in burden, while countries with a lower SDI have generally experienced increases or smaller declines in burden. Health inequality analysis confirmed that the burden was gradually concentrating towards countries with a low SDI. Among the different CVDs, ischaemic heart disease causes the greatest burden in elderly individuals. Most CVD burdens increase with age, but stroke and peripheral vascular disease show markedly different distributional characteristics. In addition, the burden of hypertensive heart disease shows an unusual shift towards high-SDI countries. High systolic blood pressure was consistently the leading risk factor for CVD among elderly individuals. CONCLUSION: The burden of CVD in older people remains severe and generally tends to shift to lower-SDI countries. Policymakers need to take targeted measures to reduce its harm.
Asunto(s)
Enfermedades Cardiovasculares , Cardiopatías , Hipertensión , Anciano , Humanos , Enfermedades Cardiovasculares/epidemiología , Carga Global de Enfermedades , Disparidades en el Estado de SaludRESUMEN
Objectives: This longitudinal study was designed to examine the growth trajectory of depressive symptoms among early-stage college students and how the development of vigorous, moderate, and light leisure-time physical activity (LTPA) was related to the growth trajectory. Participants: Four hundred and eighty-eight first- and second-year undergraduate students completed measures of depressive symptoms and LTPA at the beginning, middle, and end of a semester. Methods: Latent growth mixture modeling (LGMM) was conducted. Results: On average, students reported mild levels of depressive symptoms with significant variability at the semester start, but the symptoms elevated over time. LGMM identified two trajectories: low/gradual (75.8%) and high/increasing (24.2%). For both groups, neither vigorous nor moderate LTPA development predicted the growth trajectory of depressive symptoms. However, the change of light LTPA was negatively and significantly associated with the growth trajectory. Even when controlling for covariances, increased light LTPA still had a unique effect on buffering depressive symptoms. Conclusion: There is great potential in targeting comprehensive LTPA strategies to improve college students' mental health and promote an active lifestyle.
