1.Exploring the Antidepressant Mechanisms of Citron and Bergamot Based on Network Pharmacology and BDNF/TrkB/CREB Signaling Pathways
Meiqing SONG ; Qian YANG ; Qiming ZHONG ; Yanyan NIU ; Liguo TONG ; Jianyue XING ; Mali FENG ; Lili JIA
World Science and Technology-Modernization of Traditional Chinese Medicine 2025;27(4):1136-1149
Objective Using network pharmacology research methods and animal pharmacology experiments,explore the mechanism of antidepressant effects of traditional Chinese medicine Citron and Bergamot.Methods Using the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform(TCMSP),ETCM,Symmap,Swiss Target Prediction,and Uniprot data platforms,screen the active ingredients and corresponding gene targets of Citron and Bergamot.Obtain depression gene targets using OMIM,TTD,and Cenecards data platforms.Using Venny 2.1 online software,draw Venn diagrams of the intersection of active ingredients and gene targets.Draw network diagrams between drugs,active ingredients,targets,and diseases using Cytoscape 3.7.2 software.Construct a protein-protein interaction(PPI)network diagram using the STRING data platform for intersecting genes.Using the Metascape data platform,perform gene ontology(GO)function and Kyoto Encyclopedia of Genesand and Genomes(KEGG)pathway enrichment analysis.A rat depression model was established using chronic unpredictable mild stress(CUMS)combined with solitary care,and animal experiments were conducted to verify the BDNF/TrkB/CREB signaling pathway obtained from network pharmacology research.Results The research results of network pharmacology methods show that there are 57 antidepressant active ingredients in Citron,65 antidepressant active ingredients in Bergamot,and important active ingredients include Acetic acid,3,4,7-trimethoxycoumarin and Citric acid,etc.Through the data platform,2717 depression targets and 430 intersection targets were identified.Through PPI network analysis,key gene targets for antidepressant effects in Citron and Bergamot were identified,including TP53,Protein kinase B1,CREB-binding protein,Brain derived neurotrophic factor,etc.Through KEGG analysis,it was found that important signaling pathways include pathways in cancer,PI3K-Akt signaling pathway,Neurotrophin signaling pathway,etc.By observing the neurotrophic factor BDNF/TrkB/CREB signaling pathway in depressed rats,the results showed that the medium dose groups of Citron and Bergamot could significantly increase serum BDNF content(P<0.05),and each treatment group could improve the damage of hippocampal neurons in rats.The high and medium dose groups of Citron and Bergamot significantly increased the expression of BDNF protein in the hippocampal CA1 region(P<0.05,P<0.01).Except for the low-dose group,which showed no difference in TrkB mRNA gene expression,all other treatment groups significantly increased the mRNA gene expression levels of hippocampal BDNF,TrkB and CREB(P<0.01).The medium dose group of Citron and Bergamot increased the expression of BDNF protein in the hippocampus(P<0.01),while the medium and low dose groups significantly increased the relative expression of TrkB protein in the hippocampus(P<0.05).The medium dose group showed an increasing trend in the relative expression of CREB protein.Conclusion Traditional Chinese medicine Citron and Bergamot have therapeutic effects on depression models in rats,and the mechanism of action may be related to the BDNF/TrkB/CREB signaling pathway.
2.Exploring the Antidepressant Mechanisms of Citron and Bergamot Based on Network Pharmacology and BDNF/TrkB/CREB Signaling Pathways
Meiqing SONG ; Qian YANG ; Qiming ZHONG ; Yanyan NIU ; Liguo TONG ; Jianyue XING ; Mali FENG ; Lili JIA
World Science and Technology-Modernization of Traditional Chinese Medicine 2025;27(4):1136-1149
Objective Using network pharmacology research methods and animal pharmacology experiments,explore the mechanism of antidepressant effects of traditional Chinese medicine Citron and Bergamot.Methods Using the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform(TCMSP),ETCM,Symmap,Swiss Target Prediction,and Uniprot data platforms,screen the active ingredients and corresponding gene targets of Citron and Bergamot.Obtain depression gene targets using OMIM,TTD,and Cenecards data platforms.Using Venny 2.1 online software,draw Venn diagrams of the intersection of active ingredients and gene targets.Draw network diagrams between drugs,active ingredients,targets,and diseases using Cytoscape 3.7.2 software.Construct a protein-protein interaction(PPI)network diagram using the STRING data platform for intersecting genes.Using the Metascape data platform,perform gene ontology(GO)function and Kyoto Encyclopedia of Genesand and Genomes(KEGG)pathway enrichment analysis.A rat depression model was established using chronic unpredictable mild stress(CUMS)combined with solitary care,and animal experiments were conducted to verify the BDNF/TrkB/CREB signaling pathway obtained from network pharmacology research.Results The research results of network pharmacology methods show that there are 57 antidepressant active ingredients in Citron,65 antidepressant active ingredients in Bergamot,and important active ingredients include Acetic acid,3,4,7-trimethoxycoumarin and Citric acid,etc.Through the data platform,2717 depression targets and 430 intersection targets were identified.Through PPI network analysis,key gene targets for antidepressant effects in Citron and Bergamot were identified,including TP53,Protein kinase B1,CREB-binding protein,Brain derived neurotrophic factor,etc.Through KEGG analysis,it was found that important signaling pathways include pathways in cancer,PI3K-Akt signaling pathway,Neurotrophin signaling pathway,etc.By observing the neurotrophic factor BDNF/TrkB/CREB signaling pathway in depressed rats,the results showed that the medium dose groups of Citron and Bergamot could significantly increase serum BDNF content(P<0.05),and each treatment group could improve the damage of hippocampal neurons in rats.The high and medium dose groups of Citron and Bergamot significantly increased the expression of BDNF protein in the hippocampal CA1 region(P<0.05,P<0.01).Except for the low-dose group,which showed no difference in TrkB mRNA gene expression,all other treatment groups significantly increased the mRNA gene expression levels of hippocampal BDNF,TrkB and CREB(P<0.01).The medium dose group of Citron and Bergamot increased the expression of BDNF protein in the hippocampus(P<0.01),while the medium and low dose groups significantly increased the relative expression of TrkB protein in the hippocampus(P<0.05).The medium dose group showed an increasing trend in the relative expression of CREB protein.Conclusion Traditional Chinese medicine Citron and Bergamot have therapeutic effects on depression models in rats,and the mechanism of action may be related to the BDNF/TrkB/CREB signaling pathway.
3.Clinical application of compound cold and heat ablation system in adrenal functional tumors
Zhaoxia ZHANG ; Qianqian LYU ; Chao LI ; Jie WANG ; Wenjin YI ; Wenjuan YANG ; Lizhi NIU ; Ying XING
Chinese Journal of Endocrine Surgery 2025;19(4):558-562
The preferred treatment for adrenal functional tumors is laparoscopic surgical resection. However, in recent years, various ablation techniques have gradually been applied in the treatment of adrenal tumors. This report presents the successful diagnosis and treatment experience of 4 aldosterone-producing adenomas and 1 cortisol-secreting adenoma treated with a combined cold and hot ablation system at Xi’an Daxing Hospital from Dec. 2023 to Dec. 2024, providing a new treatment approach for clinical exploration.
4.The Xenomitochondrion Provides Extensive Supply for Mitochondrial Transplantation
Zhen YANG ; Wen-Peng LI ; Tian NIU ; Hui-Wen XUE ; Si-Xi ZHAO ; Xing-Bo ZHAO
Chinese Journal of Biochemistry and Molecular Biology 2025;41(2):273-283
Mitochondria are organelles in eukaryotic cells that play a crucial role in cellular energy me-tabolism,oxidative stress,heat production,and signal transduction.Mitochondrial transplantation(MT)is currently one of the most advanced techniques for treating mitochondrial dysfunction and anti-aging re-search.This study aimed to explore the feasibility and effectiveness of xenogeneic MT by transplanting mitochondria from yak(Bos grunniens),domestic cattle(Bos taurus),and horse(Equus caballus)into mice(Mus musculus).The results demonstrated that mitochondria from yak,domestic cattle,and horse could be successfully transplanted into mice and maintained in various tissues and organs of the mice for at least 14 days,as confirmed by confocal imaging,digital PCR,and DNA sequencing.MT mice exhibi-ted positive biological effects,including increased ATP content and mitochondrial DNA copy number(P<0.05),with the maximum effect observed on day 7,which was sustained until day 14.Reactive oxygen species(ROS)levels in MT mice significantly increased at 2 hours post-injection(P<0.05),then grad-ually decreased towards baseline levels by day 7 and day 14(P>0.05).These findings support the effec-tiveness of xenogeneic MT and suggest that the effects can be maintained for up to 14 days.This study provides scientific evidence for future clinical applications.
5.Clinical application of compound cold and heat ablation system in adrenal functional tumors
Zhaoxia ZHANG ; Qianqian LYU ; Chao LI ; Jie WANG ; Wenjin YI ; Wenjuan YANG ; Lizhi NIU ; Ying XING
Chinese Journal of Endocrine Surgery 2025;19(4):558-562
The preferred treatment for adrenal functional tumors is laparoscopic surgical resection. However, in recent years, various ablation techniques have gradually been applied in the treatment of adrenal tumors. This report presents the successful diagnosis and treatment experience of 4 aldosterone-producing adenomas and 1 cortisol-secreting adenoma treated with a combined cold and hot ablation system at Xi’an Daxing Hospital from Dec. 2023 to Dec. 2024, providing a new treatment approach for clinical exploration.
6.Kidney Gastrin/CCKBR Attenuates Type 2 Diabetes Mellitus by Inhibiting SGLT2-Mediated Glucose Reabsorption through Erk/NF-κB Signaling Pathway
Xue ZHANG ; Yuhan ZHANG ; Yang SHI ; Dou SHI ; Min NIU ; Xue LIU ; Xing LIU ; Zhiwei YANG ; Xianxian WU
Diabetes & Metabolism Journal 2025;49(2):194-209
Background:
Both sodium-glucose cotransporters (SGLTs) and Na+/H+ exchangers (NHEs) rely on a favorable Na-electrochemical gradient. Gastrin, through the cholecystokinin B receptor (CCKBR), can induce natriuresis and diuresis by inhibiting renal NHEs activity. The present study aims to unveil the role of renal CCKBR in diabetes through SGLT2-mediated glucose reabsorption.
Methods:
Renal tubule-specific Cckbr-knockout (CckbrCKO) mice and wild-type (WT) mice were utilized to investigate the effect of renal CCKBR on SGLT2 and systemic glucose homeostasis under normal diet, high-fat diet (HFD), and HFD with a subsequent injection of a low dose of streptozotocin. The regulation of SGLT2 expression by gastrin/CCKBR and the underlying mechanism was explored using human kidney (HK)-2 cells.
Results:
CCKBR was downregulated in kidneys of diabetic mice. Compared with WT mice, CckbrCKO mice exhibited a greater susceptibility to obesity and diabetes when subjected to HFD.
7.Kidney Gastrin/CCKBR Attenuates Type 2 Diabetes Mellitus by Inhibiting SGLT2-Mediated Glucose Reabsorption through Erk/NF-κB Signaling Pathway
Xue ZHANG ; Yuhan ZHANG ; Yang SHI ; Dou SHI ; Min NIU ; Xue LIU ; Xing LIU ; Zhiwei YANG ; Xianxian WU
Diabetes & Metabolism Journal 2025;49(2):194-209
Background:
Both sodium-glucose cotransporters (SGLTs) and Na+/H+ exchangers (NHEs) rely on a favorable Na-electrochemical gradient. Gastrin, through the cholecystokinin B receptor (CCKBR), can induce natriuresis and diuresis by inhibiting renal NHEs activity. The present study aims to unveil the role of renal CCKBR in diabetes through SGLT2-mediated glucose reabsorption.
Methods:
Renal tubule-specific Cckbr-knockout (CckbrCKO) mice and wild-type (WT) mice were utilized to investigate the effect of renal CCKBR on SGLT2 and systemic glucose homeostasis under normal diet, high-fat diet (HFD), and HFD with a subsequent injection of a low dose of streptozotocin. The regulation of SGLT2 expression by gastrin/CCKBR and the underlying mechanism was explored using human kidney (HK)-2 cells.
Results:
CCKBR was downregulated in kidneys of diabetic mice. Compared with WT mice, CckbrCKO mice exhibited a greater susceptibility to obesity and diabetes when subjected to HFD.
8.Kidney Gastrin/CCKBR Attenuates Type 2 Diabetes Mellitus by Inhibiting SGLT2-Mediated Glucose Reabsorption through Erk/NF-κB Signaling Pathway
Xue ZHANG ; Yuhan ZHANG ; Yang SHI ; Dou SHI ; Min NIU ; Xue LIU ; Xing LIU ; Zhiwei YANG ; Xianxian WU
Diabetes & Metabolism Journal 2025;49(2):194-209
Background:
Both sodium-glucose cotransporters (SGLTs) and Na+/H+ exchangers (NHEs) rely on a favorable Na-electrochemical gradient. Gastrin, through the cholecystokinin B receptor (CCKBR), can induce natriuresis and diuresis by inhibiting renal NHEs activity. The present study aims to unveil the role of renal CCKBR in diabetes through SGLT2-mediated glucose reabsorption.
Methods:
Renal tubule-specific Cckbr-knockout (CckbrCKO) mice and wild-type (WT) mice were utilized to investigate the effect of renal CCKBR on SGLT2 and systemic glucose homeostasis under normal diet, high-fat diet (HFD), and HFD with a subsequent injection of a low dose of streptozotocin. The regulation of SGLT2 expression by gastrin/CCKBR and the underlying mechanism was explored using human kidney (HK)-2 cells.
Results:
CCKBR was downregulated in kidneys of diabetic mice. Compared with WT mice, CckbrCKO mice exhibited a greater susceptibility to obesity and diabetes when subjected to HFD.
9.Kidney Gastrin/CCKBR Attenuates Type 2 Diabetes Mellitus by Inhibiting SGLT2-Mediated Glucose Reabsorption through Erk/NF-κB Signaling Pathway
Xue ZHANG ; Yuhan ZHANG ; Yang SHI ; Dou SHI ; Min NIU ; Xue LIU ; Xing LIU ; Zhiwei YANG ; Xianxian WU
Diabetes & Metabolism Journal 2025;49(2):194-209
Background:
Both sodium-glucose cotransporters (SGLTs) and Na+/H+ exchangers (NHEs) rely on a favorable Na-electrochemical gradient. Gastrin, through the cholecystokinin B receptor (CCKBR), can induce natriuresis and diuresis by inhibiting renal NHEs activity. The present study aims to unveil the role of renal CCKBR in diabetes through SGLT2-mediated glucose reabsorption.
Methods:
Renal tubule-specific Cckbr-knockout (CckbrCKO) mice and wild-type (WT) mice were utilized to investigate the effect of renal CCKBR on SGLT2 and systemic glucose homeostasis under normal diet, high-fat diet (HFD), and HFD with a subsequent injection of a low dose of streptozotocin. The regulation of SGLT2 expression by gastrin/CCKBR and the underlying mechanism was explored using human kidney (HK)-2 cells.
Results:
CCKBR was downregulated in kidneys of diabetic mice. Compared with WT mice, CckbrCKO mice exhibited a greater susceptibility to obesity and diabetes when subjected to HFD.
10.Distribution of MN blood type among China's minority ethnic groups.
Wenwen WANG ; Ping CHEN ; Aowei SONG ; Wenhua WANG ; Jiameng NIU ; Lili XING ; Jiangcun YANG ; Yang SUN ; Chao ZHANG
Chinese Journal of Cellular and Molecular Immunology 2025;41(1):51-56
Objective This study aims to investigate and analyze the distribution of MN blood type among ethnic minorities in China. Methods Through a systematic retrieval of the 981 literature related to MN blood group distribution, 120 literature, meeting the criteria of this study, with complete data were selected. The literature covers 49 ethnic minorities. SPSS 26 statistical software was used to analyze the data. Results The results showed that among the 49 ethnic minorities in China, the phenotype distribution of MN blood type was MN>MM>NN, with proportions of 42.54%, 41.86%, and 15.06% respectively. The gene frequency for MN blood type exhibited a trend of m>n, with a gene frequency of m being 0.6313 and n being 0.3687. Cluster analysis divided the Chinese ethnic minorities into three groups based on the gene frequency for m, showing the characteristics of Group I>Group II>Group III. Conclusion The MN blood type characteristics in Chinese ethnic minorities show a higher frequency of the M gene compared to the N gene. The frequency of the M gene is higher in southern ethnic minorities than in northern ones. There are significant differences between southwestern ethnic minorities and the Han nationality, but no differences with long-term mixed/settled Han populations.
Humans
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China/ethnology*
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Minority Groups
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Ethnicity/genetics*
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Gene Frequency
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Asian People/genetics*
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Blood Group Antigens/genetics*

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