1.Mechanism of Zuogui Jiangtang Jieyu Prescription Against Damage to Hippocampal Synaptic Microenvironment via Suppressing GluR2/Parkin Signal-mediated Mitophagy in Rats with Diabetes-related Depression
Jian LIU ; Lin LIU ; Xiaoyuan LIN ; Wei LI ; Yuhong WANG ; Hui YANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(1):104-112
ObjectiveTo reveal the mechanism of Zuogui Jiangtang Jieyu prescription against damage to hippocampal synaptic microenvironment via suppressing glutamate receptor 2 (GluR2)/Parkin signal-mediated mitophagy in rats with diabetes-related depression (DD). MethodsEighty male SD rats underwent adaptive feeding for 5 days before the study. Ten rats were randomly assigned to the normal group. The model of DD rats was established with the rest by 2-week high-fat diet + streptozotocin (STZ) tail intravenous injection + 28 days of chronic unpredictable mild stress (CUMS) combined with isolation. The rats were randomly divided into a normal group, a model group, a GluR2 blocker group (5 μg·kg-1), a GluR2 agonist group (10 μg·kg-1), a metformin + fluoxetine group (0.18 g·kg-1 metformin + 1.8 mg·kg-1 fluoxetine), and high- and low-dose Zuogui Jiangtang Jieyu prescription groups (20.52 and 10.26 g·kg-1, respectively). The rats in the GluR2 blocker group and the GluR2 agonist group were continuously injected with CNQX and Cl-HIBO in the dentate gyrus of the hippocampus once a week starting from stress modeling, respectively, while the metformin + fluoxetine group and the high- and low-dose Zuogui Jiangtang Jieyu prescription groups were continuously given intragastric administration for 28 d at the same time of stress modeling. Depression-like behavior was evaluated by open field and forced swimming experiments. The levels of serum insulin and adenosine triphosphate (ATP) in hippocampus were detected by biochemical analysis. The levels of 5-hydroxytryptamine (5-HT) and dopamine (DA) in hippocampus were detected by enzyme-linked immunosorbent assay (ELISA). The autophagosomes of hippocampal neurons were observed by transmission electron microscopy. The morphology and structure of dendrites and spines of hippocampal neurons were evaluated by Golgi staining. Western blot detected the expression levels of GluR2 and Parkin proteins in hippocampus. The expression levels of GluR2, Parkin, regulating synaptic membrane exocytosis protein 3 (RIMS3), and postsynaptic density protein 95 (PSD95) in the dentate gyrus of the hippocampus were detected by immunofluorescence. ResultsCompared with the normal group, the model group exhibited reduced total activity distance in the open field and increased immobility time in forced swimming (P<0.01), lowered levels of serum insulin and ATP, 5-HT, and DA in hippocampus (P<0.01), increased autophagosomes of hippocampal neurons, significantly damaged morphology and structure of dendrites and spines of hippocampal neurons, decreased expression levels of GluR2, RIMS3, and PSD95 in hippocampus, and an increased Parkin expression level (P<0.05, P<0.01). Compared with the model group, the GluR2 blocker group and the GluR2 agonist group showed aggravation and alleviation of the above abnormal changes, respectively (P<0.05, P<0.01). The above depression-like behavior was significantly improved in the high- and low-dose Zuogui Jiangtang Jieyu prescription groups to different degrees. Specifically, the two groups saw elevated levels of serum insulin and ATP, 5-HT, and DA in hippocampus (P<0.05, P<0.01), restrained increase in autophagosomes and damage to morphology and structure of dendrites and spines of hippocampal neurons, up-regulated protein expression levels of GluR2, RIMS3, and PSD95, and down-regulated Parkin expression level (P<0.05, P<0.01). ConclusionZuogui Jiangtong Jieyu prescription can ameliorate the mitophagy-mediated damage to hippocampal synaptic microenvironment in DD rats, the mechanism of which might be related to the regulation of GluR2/Parkin signaling pathway.
2.Clinical study on the TCM acupoint application combined with Fuyang cupping for the treatment of chronic bronchitis with lung kidney yin deficiency syndrome
Shaona XU ; Lin LI ; Yuhong YAO ; Min ZHANG
International Journal of Traditional Chinese Medicine 2025;47(7):913-918
Objective:To evaluate the clinical efficacy of TCM acupoint application combined with Fuyang cupping in the treatment of chronic bronchitis with lung and kidney yin deficiency syndrome.Methods:A randomized controlled trial study was conducted. From July 2022 to July 2024, 96 patients with chronic bronchitis in our hospital were selected as the observation subjects and divided into two groups using a random number table method, with 48 cases in each group. The control group received treatment with Fuyang cupping, while the study group received treatment with Fuyang cupping and acupoint application. Both groups were treated continuously for 14 days. TCM syndrome scores were performed before and after treatment, and serum TNF-α, CRP, and procalcitonin (PCT) levels were detected using ELISA. Arterial oxygen partial pressure (PaO 2) and carbon dioxide partial pressure (PaCO 2) were measured using a blood gas analyzer. FVC, FEV1, and FEV1 percentage of predicted values (FEV1% predicted value) and maximum expiratory flow (PEF) were measured using a pulmonary function analyzer. The relief time of clinical symptoms such as cough, sputum production, and wheezing during the treatment period were observed and recorded, and the clinical efficacy was evaluated. Results:The total effective rate of the research group was 95.83% (46/48), while that of the control group was 79.16% (38/48), with statistical significance ( χ2=6.10, P=0.013). After treatment, the scores of cough, sputum, wheezing, wheezing, and dry throat and mouth in the study group were lower than those in the control group ( t values were 4.86, 5.89, 5.23, 4.10, 5.49, respectively, P<0.01); PaO 2 level [(95.63 ± 6.45) mmHg vs. (88.44 ± 5.76) mmHg, t=5.76] was higher than of the control group ( P<0.01), and the PaCO 2 level [(40.12 ± 4.28) mmHg vs. (45.63 ± 4.36) mmHg, t=6.25] was lower than of the control group ( P<0.01); the levels of FEV1 [(2.64 ± 0.69) L vs. (1.97 ± 0.74) L, t=4.59], FEV1% predicted value (79.25 ± 11.27 vs. 62.55 ± 10.56, t=7.49), FVC [(3.05 ± 1.04) L vs. (2.06 ± 0.96) L, t=4.85], and PEF [(241.54 ± 19.85) L/min vs. (221.36 ± 19.65) L/min, t=5.01] were higher than those in the control group ( P<0.01); the levels of TNF-α, CRP and PCT in the serum were lower than those in the control group ( t values were 4.39, 6.51 and 18.59, respectively, P<0.001). Conclusion:TCM acupoint application combined with Fuyang cupping can effectively improve the TCM syndrome score and lung function, inhibit inflammatory factor levels, and improve clinical efficacy in chronic bronchitis patients with lung and kidney yin deficiency syndrome.
3.The integration of machine learning into traditional Chinese medicine.
Yanfeng HONG ; Sisi ZHU ; Yuhong LIU ; Chao TIAN ; Hongquan XU ; Gongxing CHEN ; Lin TAO ; Tian XIE
Journal of Pharmaceutical Analysis 2025;15(8):101157-101157
Traditional Chinese medicine (TCM) is an ancient medical system distinctive and effective in treating cancer, depression, coronavirus disease 2019 (COVID-19), and other diseases. However, the relatively abstract diagnostic methods of TCM lack objective measurement, and the complex mechanisms of action are difficult to comprehend, which hinders the application and internationalization of TCM. Recently, while breakthroughs have been made in utilizing methods such as network pharmacology and virtual screening for TCM research, the rise of machine learning (ML) has significantly enhanced their integration with TCM. This article introduces representative methodological cases in quality control, mechanism research, diagnosis, and treatment processes of TCM, revealing the potential applications of ML technology in TCM. Furthermore, the challenges faced by ML in TCM applications are summarized, and future directions are discussed.
4.Engineered Escherichia coli Nissle 1917 targeted delivery of extracellular PD-L1-mFc fragment for treating inflammatory bowel disease.
Yuhong WANG ; Lin HU ; Lei WANG ; Chonghai ZHANG ; Wenhao SHEN ; Hongli YANG ; Min LI ; Xin ZHANG ; Mengmeng XU ; Muxing ZHANG ; Kai YANG ; Xiaopeng TIAN
Acta Pharmaceutica Sinica B 2025;15(11):6019-6033
Inflammatory bowel disease (IBD) is an autoimmune disorder involving complex immune regulation, where balancing localized and systemic immunosuppression is a key challenge. This study aimed to enhance the therapeutic efficacy by engineering the probiotic Escherichia coli Nissle 1917 (EcN). We removed endogenous plasmids pMUT1 and pMUT2 from wild-type EcN and expressed the mPD-L1 (19‒238 aa)-mFc fusion protein on the bacterial surface using a cytolysin A (ClyA) fragment. This modification stabilized mPD-L1 (19‒238 aa) protein expression and promoted its recruitment to outer membrane vesicles (OMVs). The engineered strain, EcNΔpMUT1/2-ClyA-mPD-L1-mFc (EcN-ePD-L1-mFc), features conditional ePD-L1-mFc expression under the araBAD promoter, enhancing gut-targeted release and reducing systemic side effects. This strain improved treatment targeting and efficiency by enabling direct ePD-L1-mFc interaction with immune cells at inflammation sites. OMVs from this strain induced Treg proliferation, inhibited effector T cell proliferation in vitro, and significantly improved intestinal inflammation and colonic epithelial barrier repair in vivo. Additionally, the bacterium restored intestinal microbiota balance, increasing Lactobacillaceae and reducing Bacteroides. This study highlights the engineered bacterium's potential for targeted intestinal immune modulation and offers a novel local IBD treatment approach with promising clinical prospects.
5.Effects and mechanisms of GLPP on antioxidant stress and immune inflammation in kidney of diabetes nephropathy mice
Danrong JIANG ; Xiaoping KANG ; Dongmei LIN ; Lianfu WANG ; Yuhong YOU
Chinese Journal of Immunology 2025;41(1):39-45
Objective:To study the effect and mechanism of ganoderma lucidum polysaccharide peptide(GLPP)on renal anti oxidative stress and immune inflammation in diabetes nephropathy mice.Methods:The C57 male mice model of diabetes nephropathy was established by streptozotocin combined with high glucose and high-fat diet.Sixty diabetes nephropathy mice were divided into model group,losartan group,GLPP group(low,medium and high dose groups),GLPP high-dose+losartan group,with 10 mice in each group,10 mice fed with normal diet as the blank group.The losartan group was given 10 mg/kg losartan by gavage,and GLPP low,medium and high dose groups was given 50,100,and 200 mg/kg GLPP by gavage,while the GLPP high-dose+losartan group were given 200 mg/kg GLPP+10 mg/kg losartan by gavage.The blank group and model group were given physiological saline by gavage.After gastric lavage,observe the diet,water intake,renal pathology,structure,and apoptosis of renal tubular epithelial cells in mice,and analyze the levels of blood biochemical indicators,immune inflammation,oxidative stress indicators,and expression of apoptosis/cycle regulatory proteins in mice.Results:Compared with the blank group,the model group showed an increase in blood biochemical indicators such as Scr,BUN,TC,TG and GSP(P<0.05),as well as inflammation indicators such as level of IL-6 and TNF-α、MCP-1 were decreased(P<0.05),the oxidative stress indicator MDA was increased,T-AOC,GSH-PX,SOD were decreased(P<0.05),the apoptosis rate of renal tubular epithelial cells were increased(P<0.05),the expression levels of Bax,Caspase-3,P53,P21 were all increased,and the expression levels of Bcl-2 and Cyclin D1 were decreased(P<0.05).Compared with the model group,the losartan group,GLPP dose groups,GLPP high-dose+losartan group Scr,BUN,TC,TG,GSP,IL-6,TNF-α,MCP-1,MDA levels,apoptosis rate of renal tubular epithelial cells,Bax,Caspase-3,P53,P21 expression levels were all reduced,while T-AOC,SOD,GSH-PX levels,Bcl-2,and Cyclin D1 expression levels were all increased.Renal pathological changes were improved,and mitochondrial swelling was reduced.The GLPP high-dose+losartan group showed the most significant improvement(P<0.05).Conclusion:GLPP can reverse the renal injury in diabetes nephropathy mice,which may be related to the inhibition of apoptosis of renal tubular epithelial cells by alleviating renal oxidative stress and immune inflammatory damage.
6.Clinical guideline for vertebral augmentation of acute symptomatic osteoporotic thoracolumbar compression fractures (version 2025)
Bolong ZHENG ; Wei MEI ; Yanzheng GAO ; Liming CHENG ; Jian CHEN ; Qixin CHEN ; Liang CHEN ; Xigao CHENG ; Jian DONG ; Jin FAN ; Shunwu FAN ; Xiangqian FANG ; Zhong FANG ; Shiqing FENG ; Haoyu FENG ; Haishan GUAN ; Yong HAI ; Baorong HE ; Lijun HE ; Yuan HE ; Hua HUI ; Weimin JIANG ; Junjie JIANG ; Dianming JIANG ; Xuewen KANG ; Hua GUO ; Jianjun LI ; Feng LI ; Li LI ; Weishi LI ; Chunde LI ; Qi LIAO ; Baoge LIU ; Xiaoguang LIU ; Xuhua LU ; Shibao LU ; Bin LIN ; Chao MA ; Xuexiao MA ; Renfu QUAN ; Limin RONG ; Honghui SUN ; Tiansheng SUN ; Yueming SONG ; Hongxun SANG ; Jun SHU ; Jiacan SU ; Jiwei TIAN ; Xinwei WANG ; Zhe WANG ; Zheng WANG ; Zhengwei XU ; Huilin YANG ; Jiancheng YANG ; Liang YAN ; Feng YAN ; Guoyong YIN ; Xuesong ZHANG ; Zhongmin ZHANG ; Jie ZHAO ; Yuhong ZENG ; Yue ZHU ; Rongqiang ZHANG
Chinese Journal of Trauma 2025;41(9):805-818
Acute symptomatic osteoporotic thoracolumbar compression fracture (ASOTLF) can lead to chronic low back pain, kyphosis deformity, pulmonary dysfunction, loss of mobility, and even life-threatening complications. Vertebral augmentation is currently the mainstream treatment method for this condition. In 2019, the Editorial Board of Chinese Journal of Trauma and the Spinal Trauma Group of Orthopedic Surgeons Branch of Chinese Medical Doctor Association collaboratively led the development of Clinical guideline for vertebral augmentation for acute symptomatic osteoporotic thoracolumbar compression fractures. Six years later, with advances in clinical diagnosis and treatment techniques as well as accumulating evidence in related fields, the 2019 guideline requires updating. To this end, the Spinal Trauma Group of Orthopedic Surgeons Branch of Chinese Medical Doctor Association, the Spinal Health Professional Committee of China Human Health Science and Technology Promotion Association, and the Minimally Invasive Orthopedics Professional Committee of Shaanxi Medical Doctor Association have organized experts in the field to develop the Clinical guideline for vertebral augmentation of acute symptomatic osteoporotic thoracolumbar compression fractures ( version 2025) , based on the latest evidence-based medical researches. This guideline incorporates 3 recommendations retained from the 2019 version with updated strength of evidence, along with 12 new recommendations. It provides recommendations from six aspects of diagnosis, pain management, treatment option selection, prevention of postoperative complications, anti-osteoporosis therapy, and postoperative rehabilitation, aiming to provide a reference for standard treatment of vertebral augmentation for ASOTLF in hospitals at all levels.
7.Low-level laser therapy for the treatment of male infertility and erectile dysfunction
Yuanjie NIU ; Zhongcheng XIN ; Guiting LIN ; Pan DING ; Jiancheng PAN ; Yuhong FENG ; Yinglu GUO
Journal of Peking University(Health Sciences) 2025;57(4):627-632
Low-level laser therapy(LLLT),a noninvasive photobiomodulation technique,employs red or near-infrared(NIR)light(600-1 000 nm)with power outputs ranging from 5 to 500 mW.It exerts therapeutic effects through molecular mechanisms,specifically the activation of cytochrome C oxidase(CCO)and the modulation of intracellular signaling pathways.By enhancing mitochondrial adenosine triphosphate(ATP)synthesis,LLLT mitigates oxidative stress,regulates the reactive oxygen species(ROS)/glutathione peroxidase(GSH-Px)/superoxide dismutase(SOD)axis,and activates key path-ways,including phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt)and mitogen-activated pro-tein kinase/extracellular signal-regulated kinase(MAPK/ERK).These mechanisms confer antioxidant,anti-inflammatory,and pro-regenerative properties to LLLT,making it a viable intervention for dermato-logical conditions,oncological therapies,and musculoskeletal disorders.Recent preclinical studies un-derscore LLLT's potential in male reproductive health.Specifically,it ameliorates cavernosal fibrosis and endothelial dysfunction in erectile dysfunction(ED)models by upregulating the PI3K/Akt and MAPK/ERK pathways.In the context of sperm biology,LLLT enhances motility and acrosomal integrity in both fresh and cryopreserved spermatozoa.This is achieved through mitochondrial metabolic reprogramming,such as CCO-mediated electron transport chain activation,redox homeostasis restoration,and epigenetic modulation involving DNA methylation and histone acetylation.Additionally,LLLT alleviates scrotal heat-induced oligospermia by promoting seminiferous epithelial differentiation,elevating serum testoster-one levels,and suppressing lipid peroxidation.These findings highlight the translational potential of LLLT in regenerative medicine,particularly for male sexual and reproductive disorders.Future research efforts should focus on interdisciplinary collaborations spanning life sciences,engineering,and physics.The goal is to optimize laser parameters,including wavelength,irradiance,and treatment duration,and establish standardized protocols.Rigorous preclinical and clinical investigations are paramount to validate the safety,efficacy,and long-term outcomes of LLLT,ultimately paving the way for its integration into precision medicine frameworks for urological and reproductive therapies.
8.The integration of machine learning into traditional Chinese medicine
Yanfeng HONG ; Sisi ZHU ; Yuhong LIU ; Chao TIAN ; Hongquan XU ; Gongxing CHEN ; Lin TAO ; Tian XIE
Journal of Pharmaceutical Analysis 2025;15(8):1724-1737
Traditional Chinese medicine(TCM)is an ancient medical system distinctive and effective in treating cancer,depression,coronavirus disease 2019(COVID-19),and other diseases.However,the relatively abstract diagnostic methods of TCM lack objective measurement,and the complex mechanisms of action are difficult to comprehend,which hinders the application and internationalization of TCM.Recently,while breakthroughs have been made in utilizing methods such as network pharmacology and virtual screening for TCM research,the rise of machine learning(ML)has significantly enhanced their inte-gration with TCM.This article introduces representative methodological cases in quality control,mechanism research,diagnosis,and treatment processes of TCM,revealing the potential applications of ML technology in TCM.Furthermore,the challenges faced by ML in TCM applications are summarized,and future directions are discussed.
9.Effect of Zuogui Jiangtang Jieyu Formula on hippocampal H3K18la modification in a rat model of diabetes mellitus complicated with depression and prediction of related regulatory genes
Hui YANG ; Wei LI ; Shihui LEI ; Jinxi WANG ; Zhuo LIU ; Pan MENG ; Lin LIU ; Fan JIANG ; Yuhong WANG
Journal of Beijing University of Traditional Chinese Medicine 2025;48(6):791-801
Objective:
To investigate the effects of Zuogui Jiangtang Jieyu Formula (ZGJTJYF) on histone H3 lysine 18 lactylation (H3K18la) in the hippocampus of rats with diabetes mellitus complicated with depression (DD) and predict the regulatory genes of H3K18la.
Methods:
Male Sprague-Dawley rats were divided into control, model, and positive drug (metformin [0.18 g/kg] and fluoxetine [1.8 mg/kg]) groups, and the three groups were treated with high, medium, and low ZGJTJYF doses (20.52, 10.26, and 5.13 g/kg, respectively), with 10 rats per group. After treatment, the forced swimming and water maze tests were performed to assess depressive-like behaviors and cognitive function. An enzyme-linked immunosorbent assay was used to measure blood insulin, glycosylated hemoglobin, lactate levels, and lactate content in the hippocampus. Western blotting was used to detect H3K18la expression in the hippocampus. Cleavage Under Targets and lagmentation(CUT&Tag) experiments targeted hippocampal H3K18la epigenetic modification regions to analyze the transcription factors bound by H3K18la. Kyoto Encyclopedia of Genes and Genomes and Protein-Protein Interaction networks were constructed to identify key pathways and target genes regulated by H3K18la.
Results:
Compared with the normal group, the model group rats showed prolonged immobility time in the forced swim test, increased escape latency in the water maze experiment, decreased target quadrant distance ratio (P<0.01), increased serum lactate content, and decreased lactate content in hippocampal homogenate (P<0.01), as well as decreased H3K18la protein expression in the hippocampus (P<0.01). Compared with the model group, ZGJTJYF reduced the immobility time in the forced swim test and the escape latency in the water maze test (P<0.01), while the distance ratio in the target quadrant increased (P<0.01) in model rats. Lowered fasting blood glucose, insulin, and glycosylated hemoglobin levels (P<0.05, P<0.01) were also observed. ZGJTJYF also increased the lactate content and H3K18la protein expression in hippocampal homogenate (P<0.05, P<0.01). The DNA sequences bound by H3K18la were predominantly enriched at the transcription start sites. ZGJTJYF modulated H3K18la-associated pathways, including cell adhesion junctions, tumor growth factor-beta (TGF-β) signaling, stem cell pluripotency regulation, mitogen-activated protein kinase(MAPK) signaling pathway, and insulin resistance, leading to the identification of 12 target genes.
Conclusion
ZGJTJYF enhances hippocampal lactate levels and H3K18la modification in DD rats, which may regulate neural cell interactions, neurogenic stem cell function, TGF-β signaling, MAPK signaling, and insulin resistance pathways.
10.Effects and mechanisms of GLPP on antioxidant stress and immune inflammation in kidney of diabetes nephropathy mice
Danrong JIANG ; Xiaoping KANG ; Dongmei LIN ; Lianfu WANG ; Yuhong YOU
Chinese Journal of Immunology 2025;41(1):39-45
Objective:To study the effect and mechanism of ganoderma lucidum polysaccharide peptide(GLPP)on renal anti oxidative stress and immune inflammation in diabetes nephropathy mice.Methods:The C57 male mice model of diabetes nephropathy was established by streptozotocin combined with high glucose and high-fat diet.Sixty diabetes nephropathy mice were divided into model group,losartan group,GLPP group(low,medium and high dose groups),GLPP high-dose+losartan group,with 10 mice in each group,10 mice fed with normal diet as the blank group.The losartan group was given 10 mg/kg losartan by gavage,and GLPP low,medium and high dose groups was given 50,100,and 200 mg/kg GLPP by gavage,while the GLPP high-dose+losartan group were given 200 mg/kg GLPP+10 mg/kg losartan by gavage.The blank group and model group were given physiological saline by gavage.After gastric lavage,observe the diet,water intake,renal pathology,structure,and apoptosis of renal tubular epithelial cells in mice,and analyze the levels of blood biochemical indicators,immune inflammation,oxidative stress indicators,and expression of apoptosis/cycle regulatory proteins in mice.Results:Compared with the blank group,the model group showed an increase in blood biochemical indicators such as Scr,BUN,TC,TG and GSP(P<0.05),as well as inflammation indicators such as level of IL-6 and TNF-α、MCP-1 were decreased(P<0.05),the oxidative stress indicator MDA was increased,T-AOC,GSH-PX,SOD were decreased(P<0.05),the apoptosis rate of renal tubular epithelial cells were increased(P<0.05),the expression levels of Bax,Caspase-3,P53,P21 were all increased,and the expression levels of Bcl-2 and Cyclin D1 were decreased(P<0.05).Compared with the model group,the losartan group,GLPP dose groups,GLPP high-dose+losartan group Scr,BUN,TC,TG,GSP,IL-6,TNF-α,MCP-1,MDA levels,apoptosis rate of renal tubular epithelial cells,Bax,Caspase-3,P53,P21 expression levels were all reduced,while T-AOC,SOD,GSH-PX levels,Bcl-2,and Cyclin D1 expression levels were all increased.Renal pathological changes were improved,and mitochondrial swelling was reduced.The GLPP high-dose+losartan group showed the most significant improvement(P<0.05).Conclusion:GLPP can reverse the renal injury in diabetes nephropathy mice,which may be related to the inhibition of apoptosis of renal tubular epithelial cells by alleviating renal oxidative stress and immune inflammatory damage.


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