Network pharmacology combined with lipidomics to reveal the regulatory effects and mechanisms of Kangzao granules in the hypothalamus of rats with central precocious puberty.

Central precocious puberty (CPP) is a prevalent endocrine disorder that primarily affects children, specifically females, and is associated with various physical and psychological complications. Although Kangzao granules (KZG) are efficacious in managing CPP, the underlying mechanisms remain unclear. Therefore, this study aimed to elucidate the therapeutic mechanisms of KZG using network pharmacology, molecular docking, pharmacodynamics, and pathway validation. A putative compound-target-pathway network was constructed using Cytoscape, before KEGG and Gene Ontology enrichment analyses were conducted. Moreover, molecular docking was performed using AutoDockTools. Quality control of the 10 key components of KZG was carried out using UHPLC-ESI/LTQ-Orbitrap-MS/MS, and hypothalamic lipids were analyzed using UHPLC-Q-Exactive Orbitrap MS/MS. In total, 87 bioactive compounds that targeting 110 core proteins to alleviate CPP were identified in KZG. Lipidomic analysis revealed 18 differential lipids among the CPP, KZG, and control groups, wherein fatty acids were significantly reduced in the model group; however, these changes were effectively counteracted by KZG treatment. Molecular docking analysis revealed a strong binding affinity between flavonoids and RAC-alpha serine/threonine-protein kinase (AKT) when docked into the crystal structure. Moreover, a substantial disruption in lipid metabolism was observed in the model group; however, treatment with KZG efficiently reversed these alterations. Furthermore, the phosphoinositide 3-kinase/AKT signaling pathway was identified as a pivotal regulator of hypothalamic lipid metabolism regulator. Overall, this study highlights the effectiveness of a multidisciplinary approach that combines network pharmacology, lipidomics, molecular docking, and experimental validation in the elucidation of the therapeutic mechanisms of KZG in CPP treatment.

[Association between some factors in maternal pregnancy and childhood asthma with an onset before 3 years of age].

OBJECTIVE: To study the association between some factors in maternal pregnancy and childhood asthma with an onset before 3 years of age, and to provide a basis for the prevention and treatment of childhood asthma and further research on its pathogenesis. METHODS: A retrospective clinical epidemiological study was carried out in 100 children with asthma (age of onset<3 years) and 100 children without allergic disease who were randomly selected as controls. The related information of children and mothers was investigated by questionnaire survey, including general information, medical history, personal and family allergic history, perinatal data, and mothers' health and lifestyle during their pregnancy such as diet, disease, and environmental exposure. The main survey indices were preliminarily analyzed, selected, and assigned, and then the data were subjected to univariate and multivariate logistic regression analyses. RESULTS: The univariate and multivariate logistic regression analyses showed that the fetal sex, history of atopic disease before pregnancy, history of respiratory infection in pregnancy, and the intake of fish, shrimp, crab, meat and spicy food in pregnancy were significantly associated with childhood asthma with an onset before 3 years of age, with odds ratios of 2.868, 5.051, 4.640, 3.746, 2.971, 3.075, and 2.225, respectively. CONCLUSIONS: Many factors in maternal pregnancy are associated with childhood asthma with an onset before 3 years of age, and the risk of which can be reduced by the prevention of respiratory infection and appropriate diet in pregnancy.

Effects of astragaloside IV on IFN-gamma level and prolonged airway dysfunction in a murine model of chronic asthma.

Astragaloside IV (AST) is the main active constituent of Radix Astragali, a Chinese herb traditionally used to prevent asthma attack from chronic asthma patients. Its efficacy and action mechanisms in asthma attack prevention remain nonetheless to be further explored. In this study, chronic asthma was induced exposing ovalbumin (OVA) sensitized mice to repeated OVA challenges twice every two weeks for 12 weeks. Mice were treated with AST for 4 weeks just after the final challenge. In this murine model of chronic asthma, the airway dysfunction and remodeling remained severe and was accompanied with suppression of the IFN-gamma level in the bronchoalveolar lavage fluid (BALF) even four weeks after the final challenge, indicating that the airway structural changes continued to develop even after interruption of OVA challenges. However, after AST treatment, the airway hyperresponsiveness was sharply relieved, accompanied by the reduction of collagen deposition and mucus production, meanwhile the inflammatory cells were decreased but the IFN-gamma level increased in BALF. In conclusion, AST could prevent the development of chronic asthma, thus reducing asthma attacks. Our results indicated that it should be used as a supplementary therapy on preventing asthma attacks from chronic asthma patients.