Magnolol, a compound extracted from Magnolia officinalis, demonstrates potential efficacy in addressing metabolic dysfunction and cardiovascular diseases. Its biological activities encompass anti-inflammatory, antioxidant, anticoagulant, and anti-diabetic effects. Growth/differentiation factor-15 (GDF-15), a member of the transforming growth factor β superfamily, is considered a potential therapeutic target for metabolic disorders. This study investigated the impact of magnolol on GDF-15 production and its underlying mechanism. The research examined the pharmacological effect of magnolol on GDF-15 expression in vitro and in vivo, and determined the involvement of endoplasmic reticulum (ER) stress signaling in this process. Luciferase reporter assays, chromatin immunoprecipitation, and in vitro DNA binding assays were employed to examine the regulation of GDF-15 by activating transcription factor 4 (ATF4), CCAAT enhancer binding protein γ (CEBPG), and CCCTC-binding factor (CTCF). The study also investigated the effect of magnolol and ATF4 on the activity of a putative enhancer located in the intron of the GDF-15 gene, as well as the influence of single nucleotide polymorphisms (SNPs) on magnolol and ATF4-induced transcription activity. Results demonstrated that magnolol triggers GDF-15 production in endothelial cells (ECs), hepatoma cell line G2 (HepG2) and hepatoma cell line 3B (Hep3B) cell lines, and primary mouse hepatocytes. The cooperative binding of ATF4 and CEBPG upstream of the GDF-15 gene or the E1944285 enhancer located in the intron led to full-power transcription of the GDF-15 gene. SNP alleles were found to impact the magnolol and ATF4-induced transcription activity of GDF-15. In high-fat diet ApoE^-/- mice, administration of magnolol induced GDF-15 production and partially suppressed appetite through GDF-15. These findings suggest that magnolol regulates GDF-15 expression through priming of promoter and enhancer activity, indicating its potential as a drug for the treatment of metabolic disorders.
Lignans/pharmacology* ; Growth Differentiation Factor 15/metabolism* ; Animals ; Biphenyl Compounds/pharmacology* ; Endoplasmic Reticulum Stress/drug effects* ; Activating Transcription Factor 4/genetics* ; Mice ; Humans ; Male ; Magnolia/chemistry* ; CCAAT-Enhancer-Binding Proteins/genetics* ; Mice, Inbred C57BL

Pulmonary infection is one of the infectious diseases that have long plagued human health.The receptor for advanced glycation end-products(RAGE)is a non-specific,multi-ligand pat-tern recognition receptor expressed on the surface of various tissues and cells.It can bind to a series of structurally different ligands,including pathogen-associated molecular patterns from pathogenic micro-organisms.Soluble receptor for advanced glycation end-products(sRAGE)is a soluble form generated when cell surface RAGE is excessively stimulated by inflammatory cytokines.As a competitive recep-tor,it inhibits multiple RAGE-dependent cellular signaling pathways and participates in the inflamma-tory response process.This review summarized the clinical significance of serum sRAGE levels in in-fection-related pulmonary diseases,explored the biological characteristics of sRAGE in these diseases,and evaluated its clinical application value.

Objective:To explore the relationship between the life satisfaction of family caregivers and the de-gree of disability of disabled elderly people in Xinjiang Uygur and Kazak nationality,and the role of family mem-bers'participation in the relationship.Methods:A total of 431 elderly people with disabilities at home and their fam-ily caregivers(247 without family members and 184 with family members)were selected from Xinjiang Uygur and Kazak ethnic groups,and the survey was conducted with the Activity of Daily Living Scale(ADL)and Life Satis-faction Index B(LSIB).Results:The LSIB scores in family caregivers were negatively correlated with the ADL scores in the disabled elderly(r=-0.19,P＜0.01),and the family members'participation in care was positively correlated with the LSIB scores of family caregivers(r=0.52,P＜0.01).Family members'participation in care could moderate the negative effect of the ADL scores in the disabled elderly on the LSIB scores in family caregivers(β=0.08,P＜0.05).Conclusion:The involvement of family members in care has a moderating effect on the life satisfaction of Uyghur and Kazak family caregivers and the degree of disability of disabled elderly people.

Objective:To explore the influence of interpregnancy interval (IPI) on pregnancy complications in multiparas.Methods:This was a retrospective cohort study involving 7 669 singleton parturients who delivered at ≥28 gestational weeks in the Affiliated Hospital of Southwest Medical University between December 2015 and December 2020 and had given birth in the third trimester before. Clinical data were collected, including the baseline characteristics, pregnancy complications, gestational weeks at delivery, and neonatal birth weight. According to the IPI, these women were divided into five groups: <12 months ( n=350), 12-<24 months ( n=945), 24-<60 months ( n=2 544), 60-<120 months ( n=2 478), and ≥120 months ( n=1 352). Based on the recommendation of the World Health Organization, pregnant women with an IPI of 24-<60 months were the control group. A multivariate logistic model was used to adjust for confounders and calculate the risks of pregnancy complications, including gestational diabetes mellitus (GDM) and hypertensive disorders of pregnancy (HDP). The influences of maternal age and previous delivery mode on the associations between IPI and maternal complications were analyzed. Analysis of variance (ANOVA), Chi-square test, and Cochran-Mantel-Haenszel Chi-square test were used for statistical analysis. Results:Compared with the control group, the incidence of GDM and HDP increased in the 60-<120 months group ( OR=1.23, 95% CI: 1.01-1.48 and OR=1.47, 95% CI: 1.13-1.92) and ≥120 months group ( OR=1.37, 95% CI:1.07-1.78 and OR=1.92, 95% CI: 1.39-2.64); the risks of uterine rupture/postpartum hemorrhage and placental abruption increased in the <12 months group ( OR=1.54, 95% CI: 1.01-2.34) and 12-<24 months group ( OR=2.38 95% CI: 1.13-5.02), respectively. In the 60-<120 months group, the risk of GDM increased only in non-elderly women (adjusted OR=1.71, 95% CI: 1.36-2.14), so did the risks of GDM and HDP in the ≥120 months group (adjusted OR=3.11, 95% CI: 2.10-4.62 and adjusted OR=1.81, 95% CI: 1.12-2.91). Among women who had undergone a previous cesarean section, the risk of GDM increased in the ≥120 months group (adjusted OR=1.35, 95% CI: 1.00-1.81). In the 60-<120 months group and ≥120 months group, the risk of HDP increased in postpartum women (adjusted OR=1.79, 95% CI: 1.08-2.95 and adjusted OR=3.32, 95% CI: 1.91-5.77). Conclusion:IPI≥60 months is a risk factor for GDM and HDP, and the associations between IPI and maternal complications are influenced by maternal age.

Objective To explore the mechanism of miR-24 inhibiting brain injury in rats with cerebral infarction through PI3K/AKT signaling pathway.Methods Rats were divided into control group (n=10),sham group (n=10),model group (n=10) and experimental group (n=10).The middle cerebral artery occlusion method was used to establish the rat model of cerebral infarction.The sham group underwent the same operation without middle cerebral artery occlusion.The experimental group received stereotactic injection of miR-24 agomiR after modeling.HE staining was used to detect the pathological changes of cortex,TTC staining was used to detect the cerebral infarction area,qPCR was used to detect the expression level of miR-24 in brain tissue.Western blot was used to detect the expression of caspase-3,Bax and Bcl-2 in brain tissue,and the expression of PI3K,AKT and p-AKT were detected as well.Results Compared with the control group and the sham group,the neurological damage and pathological score of the model group was increased,and the neurological damage and pathological score of the miR-24 group was decreased.TTC staining showed that compared with the control group and the sham group,the cerebral infarction area of the model group was increased,and the cerebral infarction area of the miR-24 group was decreased,miR-24 in the model group was significantly decreased,while it was significantly increased in the experimental group (P<0.05).Western blot results showed that the expression of caspase-3 and Bax in the model group was significantly increased (P<0.05),and Bcl-2 was significantly decreased.The expression of caspase-3 and Bax in the experimental group was significantly decreased,and Bcl-2 was significantly increased (P<0.05).PI3K,AKT and p-AKT decreased in the model group,while PI3K,AKT and p-AKT increased in the experimental group (P<0.05). Conclusion MiR-24 can inhibit brain injury in rats with cerebral infarction,and its mechanism may be related to the phosphorylation of PI3K/AKT signaling pathway.