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

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.

In this study, we aimed to construct a non-replication mRNA platform and explore the side effects of electroporation-mediated delivery of mRNA on the mice as well as the expression features of the mRNA. With luciferase gene as a marker, in vitro transcription with T7 RNA polymerase was carried out for the synthesis of luciferase-expressed mRNA, followed by enzymatic capping and tailing. The mRNA was delivered in vivo by electroporation via an in vivo gene delivery system, and the expression intensity and duration of luciferase in mice were observed via an in vivo imaging system. The results demonstrated that the mRNA transcripts were successfully expressed both in vitro and in vivo. The electroporation-mediated delivery of mRNA had no obvious side effects on the mice. Luciferase was expressed successfully in all the mRNA-transduced mice, while the expression intensity and duration varied among individuals. Overall, the expression level peaked on the first day after electroporation and rapidly declined on the fourth day. This study is of great importance for the construction of non-replication mRNAs and their application in vaccine or antitumor drug development.
Animals ; Electroporation/methods* ; Gene Transfer Techniques ; Luciferases/metabolism* ; Mice ; RNA, Messenger/genetics*

Objective:To explore the feasibility of applying plasma with same blood group as kidney donor to ABO incompatible kidney transplantation(ABOi-KT)preconditioning of blood group O recipients with high-titer anti-A/B preformed antibody(IgM/IgG titer ≥1∶256).Methods:A total of 15 cases of blood group O ABOi-KT recipients with high-titer anti-A/B were recruited and divided into two groups of AB( n=8)and kidney donor's blood(KD, n=7)according to plasma type for plasma exchange during preconditioning phase. Clinical data of preconditioning and post-KT were recorded. Results:They received plasmapheresis(PP)(8.1±2.5)sessions in preconditioning phase, including double plasma filtration(DFPP)(4.0±1.4)sessions and plasma exchange(PE)(4.1±2.0)sessions, PP frequency was(0.8±0.1)sessions per day. No hemolysis reaction occurred during preconditioning phase. Anti-A/B titers declined as expected and fulfilled the ABOi-KT criteria(IgM/IgG titers ≤1∶8). KT was performed successfully without antibody-mediated rejection. All of them survived with normal renal function within 90 days post-KT. Levels of serum creatinine at Day 7/30/90 post-KT were(92.9±30.4), (96.2±25.9)and(103.1±28.4)μmol/L; anti-A/B IgM titers at Day 7/30/90 post-KT 1∶1-1∶32, 1∶1-1∶64 and 1∶1-1∶32; anti-A/B IgG titers at Day 7/30/90 post-KT 1∶1-1∶64, 1∶1-1∶64 and 1∶1-1∶32 respectively. No significant differences existed in count/frequency of PP sessions, levels of serum creatinine or anti-A/B titers at each observation point between AB and KD groups( P>0.05). Conclusions:Plasma with the same blood group as kidney donor is feasible for maximizing the intensity of ABOi-KT preconditioning. Favorable outcomes may be achieved through an intensified desensitization strategy on blood group O recipients with high-titer anti-A/B preformed antibody. The potential risks and long-term outcomes should be further explored.

Objective: To evaluate the effect of the "Interner Plus-based AIDS Comprehensive Prevention Service System" among MSM in Guangzhou, during 2010-2017, using a dynamic compartmental model. Methods: A dynamic compartmental model was developed to describe the HIV situation among MSM in Guangzhou. This model was parameterized on data from published literature or surveillance programs from the Guangzhou CDC. The Matlab 7.0 software was used for coding and analysis on collected data. HIV prevalence was analyzed among MSM under the status quo data and estimated the impact by the "Internet Plus" AIDS prevention services project. Results: HIV prevalence would have increased to 22.75% in 2017, and the total number of new HIV infections would have been 11 038, from 2010 to 2017, using the data status quo. Under the Guangzhou "Internet Plus" AIDS prevention services project, the prevalence of HIV among MSM from 2010 to 2017 was estimated to be 8.44%, 9.68%, 10.65%, 11.34%, 11.73%, 11.83%, 11.71% and 11.43% in Guangzhou, which were similar to the surveillance data. The total number of new infections in the past 8 years under the "Internet Plus" scenario was estimated to be 4 009. The "Internet Plus" program would have prevented 7 029 (63.68%) new infections during 2010-2017 as compared to the number, status quo. Conclusions The fitting result of dynamic compartmental model seemed more reasonable, which was applicable to predict HIV epidemic among MSM in Guangzhou, suggesting that the increase of HIV prevalence had been curbed since the "Internet Plus" project which was launched in 2010, and the "Interner Plus-based AIDS Comprehensive Prevention Service System" had achieved the purpose as planned, epidemiologically.

Objective To investigate the effect of general nursing intervention on the mental state of the patients with breast cancer undergoing chemotherapy.Methods Forty-eight breast cancer patients undergoing postoperative chemotherapy received nursing general interventions including healthy education,psychological nursing care,pantosomatous,relaxation therapy and rehabilitative exercise. All patients were evaluated by self-rating depression scale (SDS) and depression status inventory (DSI) before and after the general intervention.Result The scores of SDS and DSI after intervention were significantly lower than those before intervention (bothP<0.05).Conclusion The general nursing intervention could significantly improve patients’ psychological state and life quality,promote rehabilitation and improve their quality of life.