RESUMEN
Idiopathic pulmonary fibrosis is a progressive interstitial lung disease for which there is no curative therapy available. Repetitive alveolar epithelial injury repair, myofibroblast accumulation, and excessive collagen deposition are key pathologic features of idiopathic pulmonary fibrosis, eventually leading to cellular hypoxia and respiratory failure. The precise mechanism driving this complex maladaptive process remains inadequately understood. WD repeat and suppressor of cytokine signaling box containing 1 (WSB1) is an E3 ubiquitin ligase, the expression of which is associated strongly with hypoxia, and forms a positive feedback loop with hypoxia-inducible factor 1α (HIF-1α) under anoxic condition. This study explored the expression, cellular distribution, and function of WSB1 in bleomycin (BLM)-induced mouse lung injury and fibrosis. WSB1 expression was highly induced by BLM injury and correlated with the progression of lung fibrosis. Significantly, conditional deletion of Wsb1 in adult mice ameliorated BLM-induced pulmonary fibrosis. Phenotypically, Wsb1-deficient mice showed reduced lipofibroblast to myofibroblast transition, but enhanced alveolar type 2 proliferation and differentiation into alveolar type 1 after BLM injury. Proteomic analysis of mouse lung tissues identified caveolin 2 as a potential downstream target of WSB1, contributing to BLM-induced epithelial injury repair and fibrosis. These findings unravel a vital role for WSB1 induction in lung injury repair, thus highlighting it as a potential therapeutic target for pulmonary fibrosis.
Asunto(s)
Fibrosis Pulmonar Idiopática , Lesión Pulmonar , Animales , Ratones , Ubiquitina-Proteína Ligasas/genética , Ubiquitina-Proteína Ligasas/metabolismo , Miofibroblastos/metabolismo , Lesión Pulmonar/patología , Proteómica , Pulmón/patología , Fibrosis , Hipoxia/patología , Fibrosis Pulmonar Idiopática/patología , Bleomicina/toxicidad , Regeneración , Péptidos y Proteínas de Señalización IntracelularRESUMEN
BACKGROUND: Previous studies have observed a link between immunophenotypes and lung cancer, both of which are closely associated with genetic factors. However, the causal relationship between them remains unclear. METHODS: Bidirectional Mendelian randomization (MR) was performed on publicly available genome-wide association study (GWAS) summary statistics to analyze the causal relationships between 731 immunophenotypes and lung cancer. Sensitivity analyses were conducted to verify the robustness, heterogeneity, and potential horizontal pleiotropy of our findings. RESULTS: Following Bonferroni adjustment, CD14- CD16+ monocyte (OR = 0.930, 95%CI 0.900-0.960, P = 8.648 × 10- 6, PBonferroni = 0.006) and CD27 on CD24+ CD27+ B cells (OR = 1.036, 95%CI 1.020-1.053, P = 1.595 × 10 - 5, PBonferroni = 0.012) were identified as having a causal role in lung cancer via the inverse variance weighted (IVW) method. At a more relaxed threshold, CD27 on IgD+ CD24+ B cell (OR = 1.035, 95%CI 1.017-1.053, P = 8.666 × 10- 5, PBonferroni = 0.063) and CD27 on switched memory B cell (OR = 1.037, 95%CI 1.018-1.056, P = 1.154 × 10- 4, PBonferroni = 0.084) were further identified. No statistically significant effects of lung cancer on immunophenotypes were found. CONCLUSIONS: The elevated level of CD14- CD16+ monocytes was a protective factor against lung cancer. Conversely, CD27 on CD24+ CD27+ B cell was a risk factor. CD27 on class-switched memory B cells and IgD+ CD24+ B cells were potential risk factors for lung cancer. This research enhanced our comprehension of the interplay between immune responses and lung cancer risk. Additionally, these findings offer valuable perspectives for the development of immunologically oriented therapeutic strategies.
Asunto(s)
Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/epidemiología , Neoplasias Pulmonares/genética , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Causalidad , Factores de RiesgoRESUMEN
Ginseng is frequently used in traditional Chinese medicine to treat neurological disorders. The primary active component of ginseng is ginsenoside, which has been classified into more than 110 types based on their chemical structures. Ginsenoside Rb1 (GsRb1)-a protopanaxadiol saponin and a typical ginseng component-exhibits anti-inflammatory, anti-oxidant, anti-apoptotic, and anti-autophagy properties in the nervous system. Neurological disorders remain a leading cause of death and disability globally. GsRb1 effectively treats neurological disorders. To contribute novel insights to the understanding and treatment of neurological disorders, we present a comprehensive review of the pharmacokinetics, actions, mechanisms, and research development of GsRb1 in neurological disorders.
RESUMEN
Coronavirus disease 2019 (COVID-19) has been circulating in many countries around the world, characterized by long incubation period, strong infectivity, strong variability, high population susceptibility and diversified transmission methods. Its causative agent is severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Compared with adult patients, the clinical manifestations of COVID-19 in children are often dominated by mild or asymptomatic infections, but children are also important virus carriers and play an important role in the transmission of the virus. In addition, some children will show excessive inflammatory response and experience serious complications such as multisystem inflammatory syndrome in children (MIS-C). At present, the research on COVID-19 in children is still imperfect. This article will review epidemiological characteristics, the mechanism of action, variant characteristics, clinical manifestations, auxiliary examinations and treatment of children with COVID-19, in order to provide help for the diagnosis, treatment and research of children with COVID-19.