RESUMEN
Objective: Glucocorticoid-induced osteoporosis (GIOP) represents a major complication arising from the long-term use of glucocorticoids, which are widely prescribed for various inflammatory and autoimmune conditions. Despite its prevalence, the current therapeutic options for GIOP are limited in terms of efficacy, safety profiles, and patient compliance. The Modified Danggui Buxue Decoction (DGBXD), a traditional Chinese herbal formulation, has shown promise in preliminary studies for its potential osteoprotective effects. The present study aimed to explore the mechanistic underpinnings of DGBXD's action on GIOP using network pharmacology and molecular docking approaches, bridging traditional medicine with modern pharmacological insights. Method: Network pharmacology is applied to screen drug-active compounds and potential core target proteins for disease treatment and to explore the drugs' therapeutic mechanisms. Result: Altogether, 78 DGBXD active compounds and 223 DGBXD-related, 146 component-disease common, and 2168 GIOP-associated target genes were obtained. The PPI network had 43 nodes and 462 edges, and a total of 10 core target genes, including TP53, JUN and MAPK3, were identified. The results of the GO enrichment analysis implied that DGBXD might participate in biological activities, including responses to oxidative stress and nutrient levels. The outcomes of the KEGG pathway enrichment analysis showed that DGBXD may treat GIOP through TNF, IL-17, and phosphatidylinositol 3-kinase (PI3K)-Akt signaling pathways. Based on to the molecular docking results, biologically active compounds (beta-carotene, formononetin, luteolin, and isorhamnetin) exhibited good binding to AKT1 and ESR1. Conclusion: DGBXD may aid in GIOP treatment by modulating multiple therapeutic targets and signaling pathways.
RESUMEN
OBJECTIVE: To study the role of interleukin-33 (IL-33) in the development and progression of bronchopulmonary dysplasia (BPD) in preterm infants. METHODS: A prospective cohort study was performed on 128 preterm infants with a gestational age of ≤32 weeks and/or a birth weight of ≤1â500 g. They were classified to a non-BPD group with 50 infants, a mild BPD group with 32 infants, a moderate BPD group with 30 infants, and a severe BPD group with 16 infants. Related data were collected, including antepartum factors of mothers (antepartum hormone and chorioamnionitis), intrapartum factors of preterm infants (sex, gestational age, birth weight, mode of birth, and birth asphyxia), treatment after birth (pulmonary surfactant, duration of invasive ventilation, duration of noninvasive ventilation, duration of parenteral nutrition, and length of hospital stay). The high-risk factors for BPD were analyzed. ELISA was used to measure the serum level of IL-33 in preterm infants on days 1, 14, and 28 after birth. The serum level of IL-33 was compared between groups at different time points after birth. The preterm infants with moderate or severe BPD were treated with conventional corticosteroid therapy (DART regimen), and the serum level of IL-33 was measured before and after treatment. RESULTS: There were significant differences between the preterm infants with BPD and those without BPD in the incidence of maternal chorioamnionitis, gestational age, birth weight, the incidence of birth asphyxia, duration of invasive ventilation, duration of noninvasive ventilation, duration of parenteral nutrition, and total length of hospital stay (P<0.05). There were significant differences in the above indices among the preterm infants with different severities of BPD (P<0.05). On days 1, 14, and 28 after birth, the infants with BPD had a significantly higher serum level of IL-33 than those without BPD, and the serum level of IL-33 tended to increase with the severity of BPD and over the time after birth (P<0.05). The preterm infants with moderate or severe BPD had a significant reduction in the serum level of IL-33 after the treatment with DART regimen (P<0.05). CONCLUSIONS: Serum IL-33 is closely associated with the development and severity of BPD. Anti-inflammatory therapy with DART regimen can decrease the serum level of IL-33.
Asunto(s)
Displasia Broncopulmonar , Interleucina-33/sangre , Femenino , Humanos , Lactante , Recién Nacido , Recien Nacido Prematuro , Embarazo , Estudios Prospectivos , Respiración ArtificialRESUMEN
BACKGROUND: Odorant-binding proteins (OBPs) and chemosensory proteins (CSPs) are two families of small water-soluble proteins involved in odor detection and subsequent signal transmission. Determination of their binding mechanisms and specificity towards different odorants is important for developing OBPs/CSPs as targets in pest control management. RESULTS: We re-annotated genes encoding putative OBPs and CSPs in the Asian citrus psyllid (Diaphorina citri) draft genome using various bioinformatic tools. Genes encoding nine OBPs (seven Classic and two Plus-C) and 12 CSPs were identified, consistent with our previous transcriptomic results. Tissue-specific and developmental expression analyses suggested that genes encoding six OBPs and four CSPs were predominantly expressed in antennae, and displayed various expression patterns in different development stages, suggesting potential involvement in olfactory perception. Competitive fluorescence binding assays with 13 candidate ligands, including known host plant volatiles, sex pheromone components and repellents, showed that DcitOBP3 could bind to various odorants, whereas DcitOBP6, 8 and 9 bound specifically to host plant terpenoids. DcitCSP1 and 12 could also bind to certain terpenoids with high binding specificity. CONCLUSION: OBP- and CSP-encoding genes were systematically identified by annotating the draft D. citri genome and those potentially involved in odorant detection and signal transmission were identified by analyzing their tissue-expression profiles and odorant-binding affinities, particularly to the peripheral molecular perception of host plant terpenoids. The identified genes may provide potential targets for efficient pest control. © 2020 Society of Chemical Industry.