1.Mechanism of Buyang Huanwutang in Inhibiting Ferroptosis and Enhancing Neurological Function Recovery After Spinal Cord Injury via GPX4-ACSL4 Axis
Luchun XU ; Guozheng JIANG ; Yukun MA ; Jiawei SONG ; Yushan GAO ; Guanlong WANG ; Jiaojiao FAN ; Yongdong YANG ; Xing YU ; Xiangsheng TANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(5):20-30
ObjectiveTo explore the mechanism by which Buyang Huanwutang regulates the glutathione peroxidase 4 (GPX4)-acyl-CoA synthetase long-chain family member 4 (ACSL4) axis to inhibit ferroptosis and promote neurological functional recovery after spinal cord injury (SCI). MethodsNinety rats were randomly divided into five groups: sham operation group, model group, low-dose Buyang Huanwutang group (12.5 g·kg-1), high-dose Buyang Huanwutang group (25 g·kg-1), and Buyang Huanwutang + inhibitor group (25 g·kg-1 + 5 g·kg-1 RSL3). The SCI model was established by using the allen method. Tissue was collected on the 7th and 28th days after operation. Motor function was assessed by using the Basso-Beattie-Bresnahan (BBB) scale. Hematoxylin-eosin (HE), Nissl, and Luxol fast blue (LFB) staining were performed to observe spinal cord histopathology. Transmission electron microscopy was used to examine mitochondrial ultrastructure. Immunofluorescence staining was used to detect the number of NeuN-positive cells and the fluorescence intensity of myelin basic protein (MBP), GPX4, and ACSL4. Real-time fluorescent quantitative polymerase chain reaction (Real-time PCR) was used to analyze the mRNA expression of GPX4 and ACSL4. Enzyme linked immunosorbent assay (ELISA) was performed to measure the levels of reactive oxygen species (ROS), malondialdehyde (MDA), glutathione (GSH), and superoxide dismutase (SOD). Colorimetric assays were used to determine the iron content in spinal cord tissue. ResultsCompared to the sham operation group, the model group exhibited significantly reduced BBB scores (P<0.01), severe pathological damage in spinal cord tissue, and marked mitochondrial ultrastructural disruption. In addition, the model group showed a decrease in the number of NeuN-positive cells (P<0.01), reduced fluorescence intensity of MBP and GPX4 (P<0.01), lower levels of GSH and SOD (P<0.01), and downregulated mRNA expression of GPX4 (P<0.01). Moreover, compared to the sham operation group, the model group had elevated levels of ROS, MDA, and tissue iron content (P<0.01), along with increased fluorescence intensity and mRNA expression of ACSL4 (P<0.01). Compared with the model group and Buyang Huanwutang + inhibitor group, the Buyang Huanwutang group showed significantly improved BBB scores (P<0.05, P<0.01) and exhibited less severe spinal cord tissue damage, reduced edema and inflammatory cell infiltration, increased neuronal survival, and more intact myelin structures. Additionally, mitochondrial ultrastructure was significantly improved in the Buyang Huanwutang group. Compared to the model group and Buyang Huanwutang + inhibitor group, the Buyang Huanwutang group significantly increased the number of NeuN-positive cells and the fluorescence intensity of MBP (P<0.05, P<0.01). Furthermore, Buyang Huanwutang significantly increased the fluorescence intensity and mRNA expression of GPX4 (P<0.01) and decreased the fluorescence intensity and mRNA expression of ACSL4 (P<0.01) compared to the model group and Buyang Huanwutang + inhibitor group. Finally, the Buyang Huanwutang group significantly decreased ROS, MDA, and tissue iron content (P<0.01) and significantly increased GSH and SOD levels (P<0.01) compared to the model group and Buyang Huanwutang + inhibitor group. ConclusionBuyang Huanwutang inhibits ferroptosis through the GPX4/ACSL4 axis, reduces secondary neuronal and myelin injury and oxidative stress, and ultimately promotes the recovery of neurological function.
2.Discovery and proof-of-concept study of a novel highly selective sigma-1 receptor agonist for antipsychotic drug development.
Wanyu TANG ; Zhixue MA ; Bang LI ; Zhexiang YU ; Xiaobao ZHAO ; Huicui YANG ; Jian HU ; Sheng TIAN ; Linghan GU ; Jiaojiao CHEN ; Xing ZOU ; Qi WANG ; Fan CHEN ; Guangying LI ; Chaonan ZHENG ; Shuliu GAO ; Wenjing LIU ; Yue LI ; Wenhua ZHENG ; Mingmei WANG ; Na YE ; Xuechu ZHEN
Acta Pharmaceutica Sinica B 2025;15(10):5346-5365
Sigma-1 receptor (σ 1R) has become a focus point of drug discovery for central nervous system (CNS) diseases. A series of novel 1-phenylethan-1-one O-(2-aminoethyl) oxime derivatives were synthesized. In vitro biological evaluation led to the identification of 1a, 14a, 15d and 16d as the most high-affinity (K i < 4 nmol/L) and selective σ 1R agonists. Among these, 15d, the most metabolically stable derivative exhibited high selectivity for σ 1R in relation to σ 2R and 52 other human targets. In addition to low CYP450 inhibition and induction, 15d also exhibited high brain permeability and excellent oral bioavailability. Importantly, 15d demonstrated effective antipsychotic potency, particularly for alleviating negative symptoms and improving cognitive impairment in experimental animal models, both of which are major challenges for schizophrenia treatment. Moreover, 15d produced no significant extrapyramidal symptoms, exhibiting superior pharmacological profiles in relation to current antipsychotic drugs. Mechanistically, 15d inhibited GSK3β and enhanced prefrontal BDNF expression and excitatory synaptic transmission in pyramidal neurons. Collectively, these in vivo proof-of-concept findings provide substantial experimental evidence to demonstrate that modulating σ 1R represents a potential new therapeutic approach for schizophrenia. The novel chemical entity along with its favorable drug-like and pharmacological profile of 15d renders it a promising candidate for treating schizophrenia.
3.Discovery of toad-derived peptide analogue targeting ARF6 to induce immunogenic cell death for immunotherapy of hepatocellular carcinoma.
Dihui XU ; Xiang LV ; Meng YU ; Ao TAN ; Jiaojiao WANG ; Xinyi TANG ; Mengyuan LI ; Wenyuan WU ; Yuyu ZHU ; Jing ZHOU ; Hongyue MA
Journal of Pharmaceutical Analysis 2025;15(3):101038-101038
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4.Application of the deep teaching concept in early emergency nursing teaching for eye battle injuries
Jifang HE ; Jiaojiao LI ; Yue ZHONG ; Caili YUAN ; Yuzhu HU ; Juan YU ; Jiao LIU
Chinese Journal of Medical Education Research 2024;23(4):517-521
Objective:To investigate the application effect of early emergency nursing teaching for eye battle injuries guided by the deep teaching concept.Methods:A total of 64 ophthalmic nurses who participated in early emergency nursing training for eye battle injuries were divided into control group with 26 nurses and observation group with 38 nurses. For the control group, list-based self-directed learning was used for theoretical teaching, and the traditional demonstration teaching method was used for the teaching of operational skills; for the observation group, the deep teaching concept was used for teaching design from the aspects of promoting understanding, inspiring reflection, and providing immersive experience, and it is also used to implement theoretical and practical teaching. The two groups were compared in terms of general information, theoretical scores, operational skill scores, and core competency scores before and after implementation. SPSS 22.0 was used for the t-test and the chi-square test. Results:There were no significant differences between the two groups in the general information including age, years of working in ophthalmology, education background, and professional title. Before implementation, there were no significant differences between the two groups in theoretical score, operational skill score, and core competency score, and compared with the control group after implementation, the observation group had significantly better theoretical score [(90.13±5.87) vs. (81.73±4.68), P<0.001] and scores of two operational skills [(95.63±2.81) vs. (87.31±4.51), P<0.001; (96.24±2.74) vs. (89.08±4.50), P <0.001]. Compared with the control group in terms of Competency Inventory for Registered Nurse, the observation group had significantly better scores of critical thinking [(34.00±1.93) vs. (30.58±3.01), P<0.001] and clinical nursing ability [(32.13±1.65) vs. (28.35±2.28), P<0.001]. Conclusions:The teaching method based on the deep teaching concept helps to enhance the knowledge, emergency skills, clinical reflection, and nursing abilities of ophthalmic nurses in the early emergency treatment of eye battle injuries and can improve the ideological awareness and training readiness of military clinical nurses.
5.Preliminary investigation of microarray-based analysis of DDX5 affecting head and neck squamous cell car-cinoma
Guoqi LIU ; Chunxia LIU ; Jingjing WANG ; Jinhua ZUO ; Fang WANG ; Jiaojiao SONG ; Donglin YU ; Xian-Grui MA ; Wenlong WANG
Journal of Practical Stomatology 2024;40(6):810-816
Objective:To investigate the expression and role of DEAD-box RNA helicases 5(DDX5 helicases)in head and neck squamous carcinoma(HNSCC).Methods:Tissue microarray microarray was used to assess relevant mRNA expression profile data,and R software was used to screen differential mRNAs(DEGs).The expression level of DDX5 was predicted using GEPIA 2,TCGA databases,and detected by immunohistochemistry,western blot and RT-qPCR in the HNSCC tissue and cell lines.Based on high-throughput sequencing data of DECs,differentially expressed miRNAs(DEMIs)relevant DDX5 competitive endogenous RNA network(ceRNA)was constructed.The software cytoscape was used to visualize the ceRNA network map and further screen the regulatory ax-is.Results:The results of microarray screening revealed that DDX5 expression in HNSCC was upregulated.Immunohistochemistry ver-ified that DDX5 was stronger expressed in the nuclei of squamous carcinoma cells.qPCR results suggested that significant expression of DDX5 mRNA at the tissue and cellular levels(P<0.05).Western blot results showed high expression of DDX5 protein in the tissues.The ceRNA network was constructed,from which the relevant HNSCC axis circRNA-039626-miR-222-5p-DDX5 was identified.Con-clusion:DDX5 is highly expressed in HNSCC,and the circRNA-039626-miR-222-5p-DDX5 axis may be a potential regulatory axis for the development of HNSCC.
6.Effect of multi-target transcranial direct current stimulation on performance of working memory-postural control dual-task in healthy adults
Zhining ZHOU ; Rong ZHOU ; Yanwen XIAO ; Bowen WANG ; Jiaojiao LÜ ; Yu LIU
Chinese Journal of Rehabilitation Theory and Practice 2024;30(1):21-28
ObjectiveTo investigate the effect of multi-target transcranial direct current stimulation (tDCS) and single-target tDCS on the performance of working memory-postural control dual-task in healthy adults, and to compare the regulatory effect of the two stimulation protocols. MethodsFrom November, 2020 to February, 2021, 19 healthy adults in Shanghai University of Sport were recruited and randomly accepted multi-target tDCS, single-target tDCS and sham stimulation with at least one week interval between any two stimulation protocols. The target areas of multi-target tDCS included left dorsal lateral prefrontal cortex (L-DLPFC) and bilateral primary motor cortex (M1), and single-tDCS only applied to L-DLPFC. Before and after stimulation, participants completed walking and standing balance tests under single task and dual-task conditions with the second task being a N-back task. The dual-task postural control performance, dual-task cost (DTC) and working memory performance were observed before and after stimulation. ResultsSignificant differences were observed among three stimulation protocols in the changes of stride variability (F = 3.792, P = 0.029), DTC of stride variability (F = 3.412, P = 0.040) and velocity of center of pressure (Vcop) (F = 3.815, P = 0.029). The stride variability (P = 0.047) and Vcop (P = 0.015) were significantly lower and the decrease in DTC of stride variability tended to be significant (P = 0.073) following multi-target tDCS, as compared to sham stimulation. Single-target tDCS significantly decreased the changes of stride variability (P = 0.011), DTC of stride variability (P = 0.014) and Vcop (P = 0.025), as compared to sham stimulation. Compared with single target tDCS, multi-target tDCS reduced the changes of the dual-task cost of the area of center of pressure (P = 0.035). Moreover, no significant difference was observed among the three stimulation protocols in the changes of each measure in the working memory test (P > 0.05). ConclusionBoth multi-target tDCS and single-target tDCS can improve the performance of working memory-postural control dual-task in healthy adults, and compared with single-target tDCS, multi-target tDCS has some advantages in regulating postural control.
7.Relationship between macular microcirculation,cytokines and anti-VEGF efficacy in DME patients
Yu JIN ; Miao LIU ; Fangxiu YUAN ; Ling WANG ; Qiongjuan ZENG ; Yuzhen ZHU ; Jiaojiao TU ; Jun WANG
China Modern Doctor 2024;62(31):18-22
Objective To investigate the changes of macular microcirculation and aqueous humor cytokine expression in patients with diabetic macular edema(DME)after anti-vascular endothelial growth factor(VEGF)treatment,and analyze the relationship with efficacy.Methods A total of 62 patients(91 eyes)with DME who were treated in the First Hospital of Nanchang from October 2021 to August 2023 were selected and treated with intravitreal injection of conbercept.According to the reduction of central macular thickness(CMT),they were divided into efficacy significant group(CMT reduction≥100μm,59 eyes)and non-efficacy significant group(CMT reduction<100μm or increase,32 eyes).The changes of CMT,vessel density(VD)of superficial capillary plexus(SCP),fovea avascular area(FAZ),VEGF,interleuki(IL)-6,IL-8,and IL-10 after anti-VEGF treatment were analyzed.Receiver operating characteristic(ROC)curve was used to evaluate the predictive value of each index.Results Before treatment,the levels of VEGF and IL-10 in aqueous humor in efficacy significant group were significantly higher than those in non-efficacy significant group,and the level of IL-8 was significantly lower than that in non-efficacy significant group(P<0.05).After treatment,levels of VEGF,IL-6,IL-8 and IL-10 in aqueous humor in both groups were significantly lower than before treatment(P<0.05).The levels of VEGF,IL-6 and IL-8 in aqueous humor in efficacy significant group were significantly lower than those in non-efficacy significant group,and the level of IL-10 was significantly higher than that in non-efficacy significant group(P<0.05).Before and after anti-VEGF treatment,there were no significant changes in FAZ area and SCP-VD in both groups(P>0.05).Correlation analysis showed that VEGF(r=0.571,P<0.001)and IL-10(r=0.382,P=0.008)in aqueous humor at baseline were positively correlated with CMT reduction,IL-8 was negatively correlated with CMT reduction(r=-0.689,P<0.001).IL-6,FAZ area and SCP-VD were not correlated with CMT reduction(P>0.05).Cytokine levels were not correlated with FAZ area and SCP-VD(P>0.05).ROC curve results showed that area under the curve of IL-8,VEGF and IL-10 at baseline predicting anti-VEGF efficacy were 0.825,0.813 and 0.676,respectively.Conclusion The levels of VEGF,IL-8,and IL-10 in aqueous humor at baseline in DME patients were correlated with anti-VEGF efficacy and could predict the efficacy of anti-VEGF.
8.Research Progress on the Role of HMGB1 in Regulating the Function of Osteoarthritis Chondrocytes
Xin QI ; Xiaogang ZHANG ; Haiyang YU ; Xin CHEN ; Wenbo AN ; Zhipeng WANG ; Duoxian WANG ; Pengfei LUO ; Yixin CHEN ; Jiaojiao MA ; Wei QI ; Ziyang HU ; Jianjun LIU
Medical Journal of Peking Union Medical College Hospital 2024;15(1):141-146
Osteoarthritis (OA) is a chronic degenerative joint disease whose main characteristic is the destruction of articular cartilage, causing pain and disability in patients and seriously affecting their quality of life. OA can be induced by a variety of causes, and pathological changes in articular cartilage are considered to be one of the key driving factors for the occurrence of OA. High mobility group box-1 protein (HMGB1), as a non-histone protein in eukaryotic cells, can participate in regulating the inflammation and apoptosis process of OA chondrocytes, thus leading to the occurrence of OA. This article reviews the research on the mechanism of HMGB1 in OA chondrocytes, with a view to providing new ideas for the clinical prevention and treatment of OA.
9.Chinese Medicine Regulates Hepatocellular Carcinoma-related Signaling Pathways: A Review
Chun YU ; Fen GAO ; Lanlan ZHENG ; Cai GUO ; Yanfang HE ; Jiaojiao XIE ; Xuan ZHANG ; Yanhua MA
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(15):232-243
Hepatocellular carcinoma (HCC) is a common tumor in the digestive tract, the formation mechanism of which remains to be fully elucidated. Although surgery, radiation, chemotherapy, targeted therapy, and immunotherapy have achieved significant results in the treatment of HCC, these methods are accompanied by a considerable number of adverse reactions and complications. In recent years, Chinese medicine has shown remarkable efficacy in the treatment of HCC, and both basic experiments and clinical studies have confirmed the effectiveness of Chinese medicine, which exerts therapeutic effects via multiple components and multiple targets. However, the pathogenesis of HCC is exceptionally complex and not fully understood, which means that studies remain to be carried out regarding the specific mechanism of Chinese medicine in preventing and treating HCC. Network pharmacology and molecular biology can be employed to decipher the mechanism of Chinese medicine in the treatment of diseases. Studies have shown that Chinese medicine can regulate various pathways such as the mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt), Hedgehog, Wnt/β-catenin, nuclear factor-κB (NF-κB), Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3), and transforming growth factor-β (TGF-β)/Smad signaling pathways. Chinese medicine can exhibit its anti-HCC effects by inducing cell apoptosis, inhibiting cell proliferation and migration, and blocking the cell cycle via the above pathways. However, the specific mechanisms remain to be systematically studied. This study comprehensively reviews the regulatory effects of Chinese medicine on HCC-related signaling pathways to reveal the molecular mechanisms of Chinese medicine in the treatment of HCC. This view holds the promise of providing new targets, new perspectives, and new therapies for HCC treatment and advancing the modernization and development of Chinese medicine.
10.Buyang Huanwu decoction promotes angiogenesis and improves hemorheological parameters after cervical spinal cord injury
Luchun Xu ; Yongdong Yang ; Guozheng Jiang ; Yushan Gao ; Jiawei Song ; Yukun Ma ; Jiaojiao Fan ; Guanlong Wang ; Xing Yu ; Xiangsheng Tang
Journal of Traditional Chinese Medical Sciences 2024;11(4):456-465
Objective:
To explore the effects of Buyang Huanwu decoction (BYHWD) on vascular neogenesis and hemorheological parameters following cervical spinal cord injury (SCI).
Methods:
An acute cervical SCI model was established using 84 female Sprague–Dawley rats. Functional recovery of the rats was evaluated using the forelimb locomotor scale score, forelimb grip strength test, and Basso-Beattie-Bresnahan score. The animals were subsequently euthanized at days 7 and 28 postoperatively. The gross morphology, neuronal survival, and myelin sheath in the injured area were evaluated using hematoxylin and eosin (HE), Nissl, and luxol fast blue (LFB) staining, respectively. Immunofluorescence staining was used to observe CD31 expression 7 days post-injury. Furthermore, the expression of CD31, neuronal nuclear protein (NeuN), and myelin basic protein (MBP) were evaluated 28 days post-injury. Additionally, vascular endothelial growth factor A (VEGFA) and VEGF receptor-2 (VEGFR-2) expression was evaluated using western blotting. Whole-blood viscosity, plasma viscosity, and red blood cell aggregation were measured using a hemorheometer.
Results:
From postoperative days 3–28, motor function in the BYHWD group began to recover considerably compared to the SCI group. BYHWD effectively restored spinal cord histopathology. In addition, the number of NeuN-positive cells, and fluorescence intensity of CD31at 7 and 28 days and MBP significantly increased in the BYHWD group compared with the SCI group (all P < .05). Moreover, this decoction significantly upregulated the expression of VEGFA and VEGFR-2 (all P < .05). BYHWD improved the hemorheology results (i.e., except erythrocyte aggregation index in the low-dose group), revealing statistically significant differences compared with the SCI group (all P < .05).
Conclusion
BYHWD effectively promoted angiogenesis, improved hemorheological parameters, and protected neurons and myelin sheaths, ultimately promoting the recovery of neurological function after cervical SCI in rats. These findings suggest that BYHWD promotes vascular neogenesis through the VEGFA/VEGFR-2 pathway.


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