Quercetin alleviates hyperoxia-induced bronchopulmonary dysplasia by inhibiting ferroptosis through the MAPK/PTGS2 pathway: Insights from network pharmacology, molecular docking, and experimental evaluations.

Quercetin, a bioactive natural compound renowned for its potent anti-inflammatory, antioxidant, and antiviral properties, has exhibited therapeutic potential in various diseases. Given that bronchopulmonary dysplasia (BPD) development is closely linked to inflammation and oxidative stress, and quercetin, a robust antioxidant known to activate NRF2 and influence the ferroptosis pathway, offers promise for a wide range of age groups. Nonetheless, the specific role of quercetin in BPD remains largely unexplored. This study aims to uncover the target role of quercetin in BPD through a combination of network pharmacology, molecular docking, computer analyses, and experimental evaluations.

BCL6 attenuates hyperoxia-induced lung injury by inhibiting NLRP3-mediated inflammation in fetal mouse.

BACKGROUND: The transcriptional repressor B-cell lymphoma 6 (BCL6) has been reported to inhibit inflammation. So far, experimental evidence for the role of BCL6 in bronchopulmonary dysplasia (BPD) is lacking. Our study investigated the roles of BCL6 in the progression of BPD and its downstream mechanisms. METHODS: Hyperoxia or lipopolysaccharide (LPS) was used to mimic the BPD mouse model. To investigate the effects of BCL6 on BPD, recombination adeno-associated virus serotype 9 expressing BCL6 (rAAV9-BCL6) and BCL6 inhibitor FX1 were administered in mice. The pulmonary pathological changes, inflammatory chemokines and NLRP3-related protein were observed. Meanwhile, BCL6 overexpression plasmid was used in human pulmonary microvascular endothelial cells (HPMECs). Cell proliferation, apoptosis, and NLRP3-related protein were detected. RESULTS: Either hyperoxia or LPS suppressed pulmonary BCL6 mRNA expression. rAAV9-BCL6 administration significantly inhibited hyperoxia-induced NLRP3 upregulation and inflammation, attenuated alveolar simplification and dysregulated angiogenesis in BPD mice, which were characterized by decreased mean linear intercept, increased radical alveolar count and alveoli numbers, and the upregulated CD31 expression. Meanwhile, BCL6 overexpression promoted proliferation and angiogenesis, inhibited apoptosis and inflammation in hyperoxia-stimulated HPMECs. Moreover, administration of BCL6 inhibitor FX1 arrested growth and development. FX1-treated BPD mice exhibited exacerbation of alveolar pathological changes and pulmonary vessel permeability, with upregulated mRNA levels of pro-inflammatory cytokines and pro-fibrogenic factors. Furthermore, both rAAV9-BCL6 and FX1 administration exerted a long-lasting effect on hyperoxia-induced lung injury (≥4 wk). CONCLUSIONS: BCL6 inhibits NLRP3-mediated inflammation, attenuates alveolar simplification and dysregulated pulmonary vessel development in hyperoxia-induced BPD mice. Hence, BCL6 may be a target in treating BPD and neonatal diseases.

Molecular mechanisms of cell death in bronchopulmonary dysplasia.

Bronchopulmonary dysplasia (BPD) in neonates is the most common pulmonary disease that causes neonatal mortality, has complex pathogenesis, and lacks effective treatment. It is associated with chronic obstructive pulmonary disease, pulmonary hypertension, and right ventricular hypertrophy. The occurrence and development of BPD involve various factors, of which premature birth is the most crucial reason for BPD. Under the premise of abnormal lung structure and functional product, newborns are susceptible to damage to oxides, free radicals, hypoxia, infections and so on. The most influential is oxidative stress, which induces cell death in different ways when the oxidative stress balance in the body is disrupted. Increasing evidence has shown that programmed cell death (PCD), including apoptosis, necrosis, autophagy, and ferroptosis, plays a significant role in the molecular and biological mechanisms of BPD and the further development of the disease. Understanding the mode of PCD and its signaling pathways can provide new therapeutic approaches and targets for the clinical treatment of BPD. This review elucidates the mechanism of BPD, focusing on the multiple types of PCD in BPD and their molecular mechanisms, which are mainly based on experimental results obtained in rodents.

Genome-Wide Identification and Expression Analysis of Dof Transcription Factors in Lotus (Nelumbo nucifera Gaertn.).

Lotus (Nelumbo nucifera Gaertn.) is a traditional Chinese aquatic flower with high ornamental and economic value, but water salinity seriously affects lotus cultivation and distribution. The Dof transcription factors (TFs) play a crucial function in the regulatory network of growth and defense in plants. However, no systematic investigations of the Dof TFs in lotus have been performed. In this study, comprehensive searches of the lotus genome yielded 29 potential NnDofs. We carried out a series of standardized analyses, which include physical properties, multiple sequence alignment, phylogenetic analysis, gene structure, motif composition, cis-acting element prediction, chromosome distribution, and synteny analysis. The results showed that segment duplication probably caused the NnDofs gene family expansion. The potential functions of NnDofs in lotus development and stress conditions are speculated by promoter analysis. Furthermore, a complete expression investigation of NnDofs utilizing an RNA-seq atlas and quantitative real-time polymerase chain reaction (qRT-PCR) was performed. The majority of the NnDofs exhibit tissue-specific expression patterns, and many genes have been identified as being extremely sensitive to salt stressors. Overall, this study is the first to report a genome-wide assessment of the Dof family in lotus, and the findings offer vital insights for prospective functional studies on lotus salinity stress.

Effects of Antioxidants in Human Milk on Bronchopulmonary Dysplasia Prevention and Treatment: A Review.

Bronchopulmonary dysplasia (BPD) is a severe chronic lung illness that affects neonates, particularly premature infants. It has far-reaching consequences for infant health and their families due to intractable short- and long-term repercussions. Premature infant survival and long-term quality of life are severely harmed by BPD, which is characterized by alveolarization arrest and hypoplasia of pulmonary microvascular cells. BPD can be caused by various factors, with oxidative stress (OS) being the most common. Premature infants frequently require breathing support, which results in a hyperoxic environment in the developing lung and obstructs lung growth. OS can damage the lungs of infants by inducing cell death, inhibiting alveolarization, inducing inflammation, and impairing pulmonary angiogenesis. Therefore, antioxidant therapy for BPD relieves OS and lung injury in preterm newborns. Many antioxidants have been found in human milk, including superoxide dismutase, glutathione peroxidase, glutathione, vitamins, melatonin, short-chain fatty acids, and phytochemicals. Human milk oligosaccharides, milk fat globule membrane, and lactoferrin, all unique to human milk, also have antioxidant properties. Hence, human milk may help prevent OS injury and improve BPD prognosis in premature infants. In this review, we explored the role of OS in the pathophysiology of BPD and related signaling pathways. Furthermore, we examined antioxidants in human milk and how they could play a role in BPD to understand whether human milk could prevent and treat BPD.

Genome-wide analysis of WRKY transcription factor genes in Toona sinensis: An insight into evolutionary characteristics and terpene synthesis.

WRKY transcription factors (TFs), one of the largest TF families, serve critical roles in the regulation of secondary metabolite production. However, little is known about the expression pattern of WRKY genes during the germination and maturation processes of Toona sinensis buds. In the present study, the new assembly of the T. sinensis genome was used for the identification of 78 TsWRKY genes, including gene structures, phylogenetic features, chromosomal locations, conserved protein domains, cis-regulatory elements, synteny, and expression profiles. Gene duplication analysis revealed that gene tandem and segmental duplication events drove the expansion of the TsWRKYs family, with the latter playing a key role in the creation of new TsWRKY genes. The synteny and evolutionary constraint analyses of the WRKY proteins among T. sinensis and several distinct species provided more detailed evidence of gene evolution for TsWRKYs. Besides, the expression patterns and co-expression network analysis show TsWRKYs may multi-genes co-participate in regulating terpenoid biosynthesis. The findings revealed that TsWRKYs potentially play a regulatory role in secondary metabolite synthesis, forming the basis for further functional characterization of WRKY genes with the intention of improving T. sinensis.

[Clinical observation of improved proximal femoral locking plate in treating osteoporotic intertrochanteric fractures].

OBJECTIVE: To investigate the effects of proximal femoral locking plate (PFP) in treating osteoporotic intertrochanteric fractures and to analyze the failure cases. METHODS: Totally 32 patients with osteoporotic intertrochanteric fractures of Evans I and II were treated with improved locking PFP, including 17 males and 15 females with an average age of 77.3 years old ranging from 70 to 86 years old. After operation, according to Harris hip scores, the hip function and therapeutic effects were evaluated. RESULTS: The observed 32 patients' operative time was (60.5±15.7) min, intraoperative blood loss was (128.8±73.6) ml;perioperative blood transfusion was (224.0±72.7) ml. Hospitalization time was from 14 to 20 d with an average of 17.2 d. All patients were followed up from 6 to 18 months with an average of 14.1 months. The fracture healing time was from 3 to 6 months with an average of 3.1 months. One patient occurred internal fixation loosening and screw backward, 4 cases occurred urinary tract infection, 1 patient died of cardiovascular disease for 6 months postoperative, 2 patients died of a stroke for 1 year postoperative. No incision deep infection, peri internal fixation fractures, lower extremity deep venous thrombosis, internal fixation breakage, nonunion, severe coax vara and coax valgus occurred. The final Harris score was 89.74±6.84, the result was excellent in 10 cases, good in 16 cases, fair in 4 cases, and poor in 2 cases. CONCLUSIONS: Locking PFP can provide relative stable fixation to proximal end of osteoporotic femoral fractures, which is a good choice for the treatment of intertrochanteric fractures. It could provide stableness of fractures and bone union, even avoid screws loose or slide out.