1.Improvement of Lung Function in Rats with Idiopathic Pulmonary Fibrosis by Shengxiantang via Regulating Cell Senescence Mediated by Wnt3a/β-catenin Signaling Pathway
Yanan YAN ; Yulei LIANG ; Jiepeng WANG ; Chaoyi FANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(12):31-38
ObjectiveTo observe the effect of Shengxiantang (SXT) on cell senescence mediated by wingless/integrated (Wnt)3a/β-catenin pathway in rats with idiopathic pulmonary fibrosis (IPF) and reveal the possible mechanism in improving lung function of IPF rats. MethodA total of 32 SPF level SD rats were randomly divided into sham group, model group, pirfenidone group, and SXT group. The IPF rat model was established by intratracheal instillation of bleomycin (0.005 g·kg-1). The following day after surgery, rats in the SXT group were given the aqueous solution of SXT granules (0.78 g·kg-1), and the pirfenidone group was given pirfenidone suspension (0.05 g·kg-1). The other groups were given deionized water (10 mL·kg-1) for 28 consecutive days. Lung tissue was collected after the lung function was measured. The pathological changes of the lung tissue were observed by hematoxylin-eosin (HE) and Masson staining, and then the Szapiel score and Ashcroft score were performed. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to detect telomere length. Western blot was applied to detect the expressions of epithelial-mesenchymal transformation (EMT) markers [α-smooth muscle actin (α-SMA) and E-cadherin], telomere reverse transcriptase (TRET), aging-related proteins (p53 and p21), senescence-associated secretory phenotype [interleukin-6 (IL-6) and matrix metalloproteinase-1 (MMP-1)], and key proteins of Wnt signaling pathway [Wnt3a, glycogen synthase kinase-3β (GSK-3β), β-catenin, Cyclin D1, and c-Myc]. ResultCompared with those in the Sham group, peak expiratory flow (PEF) and minute ventilation volume (MV) in the model group were significantly decreased (P<0.01), and the frequency of respiratory (f) was significantly increased (P<0.01). The Szapiel score, Ashcroft score, and protein expression of α-SMA, p53, p21, IL-6, MMP-1, Wnt3a, GSK3β, β-catenin, Cyclin D1, and c-Myc were increased (P<0.01). The expressions of E-cadherin and TERT, as well as telomere length were significantly decreased (P<0.01). Compared with those in the model group, PEF and MV in the SXT group were significantly increased (P<0.01), while f was significantly decreased (P<0.01). The Szapiel score, Ashcroft score, and protein expression of α-SMA, p53, p21, IL-6, MMP-1, Wnt3a, GSK3β, β-catenin, Cyclin D1, and c-Myc were significantly decreased (P<0.05, P<0.01). Nevertheless, the expression of E-cadherin and TERT, as well as telomere length were significantly increased (P<0.01). ConclusionSXT presents a significant protective effect on lung function in IPF rats, and the prescription may act on the Wnt3a/β-catenin signaling pathway to regulate cell senescence induced by TERT to inhibit EMT.
2.Effects of grandparent involvement in parenting on health related behaviors among urban preschoolers
LU Yitong, ZOU Chaoyi, YAO Fang, TU Wenjuan, JIANG Kaihua, GAO Yuexia, LU Qingyun
Chinese Journal of School Health 2023;44(12):1824-1827
Objective:
To explore the effects of grandparent involvement in parenting on health related behaviors among urban preschool children, so as to provide a basis for the development of interventions for unhealthy behaviors among preschool children with different parenting pattern.
Methods:
A total of 5 431 preschool children aged 3-6 years old in Xinbei District, Changzhou City, were selected by census method during January to October, 2022. General household characteristics and health related behaviors of children were investigated by questionnaires, and the differences in health related behaviors with different parenting pattern involving grandparents were explored by the χ 2 test. A multifactorial Logistic regression model was used to analyze the effects of grandparenting on preschool children s health behaviors.
Results:
About 51.2% of preschoolers were raised by both parents, 46.1 % were co parented by grandparents, and 2.7% were raised by grandparents. After multifactorial Logistic regression analysis controlling for age, gender, annual household income, and family structure, children co parented by grandparents had a reduced risk of screen exposure time>1 h/d ( OR =0.79, P <0.05), with increased risks of outdoor activity time<2 h/d ( OR =1.30, P < 0.05 ), sleep duration <10 h/d ( OR =1.31, P <0.05), sleep difficulties ( OR =1.39, P <0.05) and adverse eating behaviors ( OR =1.20, P < 0.05), compared with children parented by both parents. Children raised by grandparents were at increased risk for outdoor activity time<2 h/d ( OR =2.19) and unhealthy eating behaviors ( OR =1.39) ( P <0.05).
Conclusions
Compared with children raised by both parents, the incidence of unhealthy behaviors is increased in children raised by parents and grandparents and in children raised by full grandparents. Active intervention should be focused on unhealthy behaviors of preschool children with pareting involving grandparents to promote the physical and mental health of preschool children.
3.Effect of Buyang Huanwutang on Keap1/Nrf2/HO-1 Antioxidant Signaling Pathway in Rats with Idiopathic Pulmonary Fibrosis
Zhe ZHANG ; Shu ZHAO ; Yunpeng HAN ; Feng JIN ; Jiarong SHANG ; Jiepeng WANG ; Chaoyi FANG
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(17):9-16
ObjectiveTo study the effect of Buyang Huanwutang on Kelch-like Ech-related protein 1 (Keap1)/nuclear factor E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) antioxidant signaling pathway in rats with idiopathic pulmonary fibrosis (IPF) and explore the mechanism of this prescription in the treatment of IPF. MethodForty SPF-grade male SD rats were assigned into a sham operation group, a model group, a Buyang Huanwutang group, and a nintedanib group according to random number table method, with 10 rats in each group. IPF rat model was established by intratracheal infusion of bleomycin (0.005 g·kg-1) in other groups except the sham operation group. Buyang Huanwutang group was administrated with Buyang Huanwutang (14.84 g·kg-1),intragastric administration of nitedanib suspension (0.1 g·kg-1),sham operation group and model group were given equal volume of normal saline, for 28 days. After lung function test, serum and lung tissue samples were collected. Hematoxylin-eosin (HE) staining and Masson trichrome staining were employed to observe the pathological changes of the lung tissue. The content of hydroxyproline (HYP) in lung tissue was detected. The levels of malondialdehyde (MDA) in serum and lung tissue, and the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) were determined. The mRNA and protein levels of Keap1, Nrf2, and HO-1 was determined by Real-time fluorescent quantitative polymerase chain reaction, immunohistochemical staining, and Western blot. ResultCompared with the sham operation group, the modeling increased the resistance and elasticity and decreased the compliance of respiratory system (P<0.01), elevated the lung index, pathological score, and HYP content in lung tissue (P<0.01), and enriched MDA in serum and lung tissue, while it decreased the activities of SOD, GSH-Px, and CAT (P<0.01). Furthermore, the modeling down-regulated the mRNA and protein levels of Keap1 and up-regulated those of Nrf2 and HO-1 in lung tissue (P<0.01). Compared with the model group, Buyang Huanwutang decreased the resistance and elasticity and increased the compliance of respiratory system (P<0.01), lowered the lung index, pathological score, and HYP content in lung tissue (P<0.01), and reduced MDA in serum and lung tissue, while it increased the activities of SOD, GSH-Px, and CAT (P<0.01). Additionally, Buyang Huanwutang down-regulated the expression of Keap1 and up-regulated that of Nrf2 and HO-1 in lung tissue (P<0.05, P<0.01). ConclusionBuyang Huanwutang can activate Keap1/Nrf2/HO-1 signaling pathway to enhance the antioxidant capacity and slow down the pathological process of IPF in rats.
4.Mechanism of Bugansan Decoction in ameliorating learning and memory impairment in D-galactose-induced aging rats based on AGEs/RAGE/NF-κB pathway
Wei LI ; Shuo WANG ; Jiepeng WANG ; Fang FANG ; Chaoyi FANG
Digital Chinese Medicine 2023;6(3):317-327
:
Objective To investigate the underlying mechanism of the compound Bugansan Decoction
(补肝散, BGSD) in intervening learning and memory in D-galactose (D-gal)-induced aging rats.
Methods:
A total of 40 rats were randomly assigned to four groups: control, model, BGSD [14.06 g/(kg·d)], and piracetam [0.4 g/(kg·d)] groups, with 10 rats in each group. D-gal [400 mg/(kg·d)] was injected intraperitoneally to establish the aging rat model. The rats' body weight, water intake, food intake, and gripping strength were recorded each week. The eightarm maze and step-down test were used to measure the rats' capacity for learning and memory. Liver, thymus, spleen, and brain tissues were weighed to calculate the corresponding organ indices; serum malondialdehyde (MDA) content and superoxide dismutase (SOD) activity were measured. Hematoxylin and eosin (HE) staining was adopted to observe the pathological changes of the hippocampus; enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β in the hippocampus. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression of receptors for advanced glycation end products (RAGE), nuclear factor-κB (NF-κB), TNF-α, IL-6, and IL-1β mRNA in the hippocampus. Western blot (WB) was employed to detect the expression levels of advanced glycation end products (AGEs), RAGE, and NF-κB protein in the hippocampus.
Results:
In D-gal-induced aging rats, BGSD significantly increased food intake, water intake, body weight, gripping strength, and organ indices (P < 0.05), and significantly decreased working memory error (WME), reference memory error (RME), and total memory errors (TE) in an eight-arm maze (P < 0.05). In the step-down test, step-down latency was prolonged and the frequency of errors dropped (P < 0.05). Additionally, BGSD could lessen the harm done to hippocampus neurons, increase serum SOD activity, lower MDA levels, and down-regulate the expression levels of the pro-inflammatory molecules TNF-α, IL-6, and IL-1β (P < 0.05). Further findings showed that BGSD significantly decreased hippocampal AGEs, RAGE, and NF-κB expression (P < 0.05).
Conclusion
By blocking the AGEs/RAGE/NF-κB signaling pathway, BGSD may regulate the neuroinflammatory damage in D-gal-induced aging rats, and thus improve learning and memory.