1.Buzhong Yiqitang Regulates Endoplasmic Reticulum Stress to Attenuate Cisplatin Resistance in Non-small Cell Lung Cancer via Nrf2/ROS Pathway
Dan YU ; Qirui MU ; He LI ; Yuetong LIU ; Jingyi HUANG ; Yuan GAO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(10):98-104
ObjectiveTo investigate the mechanism of Buzhong Yiqitang in attenuating cisplatin resistance in non-small cell lung cancer by observing the effects of Buzhong Yiqitang on endoplasmic reticulum stress-related molecules in human lung adenocarcinoma cells (A549) and cisplatin-resistant cells in human lung adenocarcinoma cells (A549/DDP) via the nuclear factor E2-related factor 2(Nrf2)/reactive oxygen species(ROS) pathway. MethodsThe serum containing Buzhong Yiqitang was prepared and A549 cells and A549/DDP cells were cultured. The cells were randomized into groups A (A549 cells+blank serum), B (A549 cells+20 mg·L-1 cisplatin+blank serum), C (A549 cells+20 mg·L-1 cisplatin+10% Buzhong Yiqitang-containing serum), D (A549/DDP cells+blank serum), E (A549/DDP cells+20 mg·L-1 cisplatin+blank serum), and F (A549/DDP cells+20 mg·L-1 cisplatin+10% Buzhong Yiqitang-containing serum). The cell counting kit-8 (CCK-8) method was used to detect the half maximal inhibitory concentration (IC50) of cisplatin. The protein levels of Nrf2 and p-Nrf2 were determined by Western blotting. The DCFH-DA fluorescent probe was used to measure the content of reactive oxygen species (ROS) in each group. The protein levels of glucose-regulated protein 78 (GRP78), activated transcription factor 6 (ATF6), and C/EBP-homologous protein (CHOP) were determined by Western blot. ResultsCompared with group B, group C showed a reduction in IC50 of cisplatin (P<0.05), which held true in group E compared with group F (P<0.05). Moreover, the IC50 of cisplatin to A549/DDP cells was higher than that to A549 cells before and after Buzhong Yiqitang intervention (P<0.05). Compared with group A, group B showed up-regulated protein levels of Nrf2 and p-Nrf2 (P<0.05). Compared with group B, group C showed down-regulated protein levels of Nrf2 and p-Nrf2 (P<0.05). Compared with group D, group E showed up-regulated protein levels of Nrf2 and p-Nrf2 (P<0.05), which, however, were significantly down-regulated in group F (P<0.05). The ROS content and the protein levels of GRP78, ATF6, and CHOP followed a descending trend of group C > group B > group A in A549 cells and group F > group E > group D in A549/DDP cells (P<0.05). Moreover, the ROS content and the protein levels of GRP78, ATF6, and CHOP in A549 cells were higher than those in A549/DDP cells before and after Buzhong Yiqitang intervention (P<0.05). ConclusionBuzhong Yiqitang may regulate endoplasmic reticulum stress via the Nrf2/ROS pathway to attenuate cisplatin resistance in non-small cell lung cancer.
2.Andrographolide as a Multi-Target Therapeutic Agent in Diabetic Nephropathy: Insights into STAT3/PI3K/Akt Pathway Modulation
Yuan YIN ; Jing HE ; Yu FANG ; Min WEI ; Wang ZHANG
Biomolecules & Therapeutics 2025;33(3):529-543
Diabetic nephropathy (DN) remains a leading cause of end-stage renal disease (ESRD), driven by chronic inflammation, oxidative stress, and apoptosis. Current therapies targeting glycemic and blood pressure control fail to address the underlying molecular mechanisms of DN. This study investigates the therapeutic potential of andrographolide (AD), a diterpenoid lactone from Andrographis paniculata, in mitigating DN by modulating key molecular pathways. Through integrative network pharmacology, molecular docking, and in vivo/in vitro experiments, 107 overlapping DN-related targets were identified, with STAT3, PI3K, and AKT1 emerging as core nodes. Molecular docking revealed high binding affinities between AD and these targets, supporting its modulatory potential. In vivo, AD significantly improved renal function in streptozotocin-induced DN rats, reducing proteinuria, glomerular hypertrophy, and renal fibrosis. AD also attenuated oxidative stress, decreased pro-inflammatory cytokine levels, and enhanced antioxidant enzyme activities, demonstrating systemic anti-inflammatory and antioxidative effects. In vitro studies further confirmed that AD alleviates podocyte oxidative stress and apoptosis under high glucose conditions by suppressing the RAGE-NF-κB and STAT3/PI3K/Akt pathways. Histological analyses revealed substantial improvements in renal architecture, including reductions in fibrosis and mesangial expansion. These results underscore AD’s multi-target mechanism, directly addressing DN’s core pathological drivers, including inflammation, oxidative stress, and apoptosis. As a natural compound with notable safety and efficacy, AD holds promise as an adjunct or standalone therapeutic agent for DN. This study establishes a robust preclinical foundation for AD, warranting further exploration in clinical trials and its potential application in other diabetic complications.
3.Andrographolide as a Multi-Target Therapeutic Agent in Diabetic Nephropathy: Insights into STAT3/PI3K/Akt Pathway Modulation
Yuan YIN ; Jing HE ; Yu FANG ; Min WEI ; Wang ZHANG
Biomolecules & Therapeutics 2025;33(3):529-543
Diabetic nephropathy (DN) remains a leading cause of end-stage renal disease (ESRD), driven by chronic inflammation, oxidative stress, and apoptosis. Current therapies targeting glycemic and blood pressure control fail to address the underlying molecular mechanisms of DN. This study investigates the therapeutic potential of andrographolide (AD), a diterpenoid lactone from Andrographis paniculata, in mitigating DN by modulating key molecular pathways. Through integrative network pharmacology, molecular docking, and in vivo/in vitro experiments, 107 overlapping DN-related targets were identified, with STAT3, PI3K, and AKT1 emerging as core nodes. Molecular docking revealed high binding affinities between AD and these targets, supporting its modulatory potential. In vivo, AD significantly improved renal function in streptozotocin-induced DN rats, reducing proteinuria, glomerular hypertrophy, and renal fibrosis. AD also attenuated oxidative stress, decreased pro-inflammatory cytokine levels, and enhanced antioxidant enzyme activities, demonstrating systemic anti-inflammatory and antioxidative effects. In vitro studies further confirmed that AD alleviates podocyte oxidative stress and apoptosis under high glucose conditions by suppressing the RAGE-NF-κB and STAT3/PI3K/Akt pathways. Histological analyses revealed substantial improvements in renal architecture, including reductions in fibrosis and mesangial expansion. These results underscore AD’s multi-target mechanism, directly addressing DN’s core pathological drivers, including inflammation, oxidative stress, and apoptosis. As a natural compound with notable safety and efficacy, AD holds promise as an adjunct or standalone therapeutic agent for DN. This study establishes a robust preclinical foundation for AD, warranting further exploration in clinical trials and its potential application in other diabetic complications.
4.Mechanism of Action of Kaixinsan in Ameliorating Alzheimer's Disease
Xiaoming HE ; Xiaotong WANG ; Dongyu MIN ; Xinxin WANG ; Meijia CHENG ; Yongming LIU ; Yetao JU ; Yali YANG ; Changbin YUAN ; Changyang YU ; Li ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(1):20-29
ObjectiveTo investigate the mechanism of action of Kaixinsan in the treatment of Alzheimer's disease (AD) based on network pharmacology, molecular docking, and animal experimental validation. MethodsThe Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and the Encyclopedia of Traditional Chinese Medicine(ETCM) databases were used to obtain the active ingredients and targets of Kaixinsan. GeneCards, Online Mendelian Inheritance in Man(OMIM), TTD, PharmGKB, and DrugBank databases were used to obtain the relevant targets of AD. The intersection (common targets) of the active ingredient targets of Kaixinsan and the relevant targets of AD was taken, and the network interaction analysis of the common targets was carried out in the STRING database to construct a protein-protein interaction(PPI) network. The CytoNCA plugin within Cytoscape was used to screen out the core targets, and the Metascape platform was used to perform gene ontology(GO) functional enrichment analysis and Kyoto encyclopedia of genes and genomes(KEGG) pathway enrichment analysis. The “drug-active ingredient-target” interaction network was constructed with the help of Cytoscape 3.8.2, and AutoDock Vina was used for molecular docking. Scopolamine (SCOP) was utilized for modeling and injected intraperitoneally once daily. Thirty-two male C57/BL6 mice were randomly divided into blank control (CON) group (0.9% NaCl, n=8), model (SCOP) group (3 mg·kg-1·d-1, n=8), positive control group (3 mg·kg-1·d-1 of SCOP+3 mg·kg-1·d-1 of Donepezil, n=8), and Kaixinsan group (3 mg·kg-1·d-1 of SCOP+6.5 g·kg-1·d-1 of Kaixinsan, n=8). Mice in each group were administered with 0.9% NaCl, Kaixinsan, or Donepezil by gavage twice a day for 14 days. Morris water maze experiment was used to observe the learning memory ability of mice. Hematoxylin-eosin (HE) staining method was used to observe the pathological changes in the CA1 area of the mouse hippocampus. Enzyme linked immunosorbent assay(ELISA) was used to determine the serum acetylcholine (ACh) and acetylcholinesterase (AChE) contents of mice. Western blot method was used to detect the protein expression levels of signal transducer and activator of transcription 3(STAT3) and nuclear transcription factor(NF)-κB p65 in the hippocampus of mice. ResultsA total of 73 active ingredients of Kaixinsan were obtained, and 578 potential targets (common targets) of Kaixinsan for the treatment of AD were screened out. Key active ingredients included kaempferol, gijugliflozin, etc.. Potential core targets were STAT3, NF-κB p65, et al. GO functional enrichment analysis obtained 3 124 biological functions, 254 cellular building blocks, and 461 molecular functions. KEGG pathway enrichment obtained 248 pathways, mainly involving cancer-related pathways, TRP pathway, cyclic adenosine monophosphate(cAMP) pathway, and NF-κB pathway. Molecular docking showed that the binding of the key active ingredients to the target targets was more stable. Morris water maze experiment indicated that Kaixinsan could improve the learning memory ability of SCOP-induced mice. HE staining and ELISA results showed that Kaixinsan had an ameliorating effect on central nerve injury in mice. Western blot test indicated that Kaixinsan had a down-regulating effect on the levels of NF-κB p65 phosphorylation and STAT3 phosphorylation in the hippocampal tissue of mice in the SCOP model. ConclusionKaixinsan can improve the cognitive impairment function in SCOP model mice and may reduce hippocampal neuronal damage and thus play a therapeutic role in the treatment of AD by regulating NF-κB p65, STAT3, and other targets involved in the NF-κB signaling pathway.
5.Andrographolide as a Multi-Target Therapeutic Agent in Diabetic Nephropathy: Insights into STAT3/PI3K/Akt Pathway Modulation
Yuan YIN ; Jing HE ; Yu FANG ; Min WEI ; Wang ZHANG
Biomolecules & Therapeutics 2025;33(3):529-543
Diabetic nephropathy (DN) remains a leading cause of end-stage renal disease (ESRD), driven by chronic inflammation, oxidative stress, and apoptosis. Current therapies targeting glycemic and blood pressure control fail to address the underlying molecular mechanisms of DN. This study investigates the therapeutic potential of andrographolide (AD), a diterpenoid lactone from Andrographis paniculata, in mitigating DN by modulating key molecular pathways. Through integrative network pharmacology, molecular docking, and in vivo/in vitro experiments, 107 overlapping DN-related targets were identified, with STAT3, PI3K, and AKT1 emerging as core nodes. Molecular docking revealed high binding affinities between AD and these targets, supporting its modulatory potential. In vivo, AD significantly improved renal function in streptozotocin-induced DN rats, reducing proteinuria, glomerular hypertrophy, and renal fibrosis. AD also attenuated oxidative stress, decreased pro-inflammatory cytokine levels, and enhanced antioxidant enzyme activities, demonstrating systemic anti-inflammatory and antioxidative effects. In vitro studies further confirmed that AD alleviates podocyte oxidative stress and apoptosis under high glucose conditions by suppressing the RAGE-NF-κB and STAT3/PI3K/Akt pathways. Histological analyses revealed substantial improvements in renal architecture, including reductions in fibrosis and mesangial expansion. These results underscore AD’s multi-target mechanism, directly addressing DN’s core pathological drivers, including inflammation, oxidative stress, and apoptosis. As a natural compound with notable safety and efficacy, AD holds promise as an adjunct or standalone therapeutic agent for DN. This study establishes a robust preclinical foundation for AD, warranting further exploration in clinical trials and its potential application in other diabetic complications.
6.Research progress on Astragali Radix for promoting healing of chronic refractory wound
Yangyang YU ; Yuan GAO ; Jinling HE ; Hao WU ; Keyu CHEN ; Yuxing ZHAO
China Pharmacy 2025;36(19):2473-2478
Chronic refractory wound (CRW) presents significant clinical treatment challenges due to pathological characteristics such as persistent inflammation, bacterial infection, oxidative stress and inadequate angiogenesis. Astragali Radix, a traditional Chinese medicinal herb, exerts multi-target pharmacological effects on CRW through its active components, including Astragalus polysaccharides, flavonoids, and astragaloside Ⅳ, etc. Fundamental studies indicate that these components promote CRW healing by modulating inflammatory responses, inhibiting pathogen growth, improving antioxidant capacity and stimulating neovascularization. Network pharmacology and bioinformatics studies have revealed that active components of Astragali Radix target and modulate key signaling nodes such as nuclear factor-κB, phosphatidylinositol 3-kinase/Akt, AMP-activated protein kinase, and vascular endothelial growth factor receptor, as well as inflammation-angiogenesis-related pathways, thereby synergistically exerting anti-inflammatory and pro-angiogenic effect. Clinical applications have demonstrated that oral formulations (e.g., Huangqi guizhi decoction, Danggui huangqi decoction, etc.) reduce healing time of CRW and lower inflammatory marker levels, while topical preparations (e.g., Zizhu ointment, Huangqi shengji ointment, electrostatically spun Astragalus polysaccharide composite nanofibre dressings, etc.) significantly improve healing rates of CRW and minimize complications.
7.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.
8.Knockdown of chemokine receptor 3 inhibits hepatoblastoma cell proliferation and migration by weakening Wnt/β-catenin signaling pathway
Dao-Kui DING ; Yu-Hang YUAN ; Yan-An LI ; Xi-Chun CUI ; He-Ying YANG ; Jia DU ; Yang-Guang SU
Chinese Pharmacological Bulletin 2024;40(12):2347-2354
Aim To investigate the role and mecha-nism of CXC chemokine receptor 3(CXCR3)in hepa-toblastoma(HB).Methods The expression of CX-CR3 was detected by immunohistochemical and West-ern blot in 16 cases of HB tissue and adjacent normal liver tissue.The HB cells(Huh-6 and HepT1)were transfected with Con-shRNA,CXCR3-shRNA1,and CXCR3-shRNA2,respectively,and then divided into the Con-shRNA group,CXCR3-shRNA1 group,and CXCR3-shRNA2 group.Cell proliferation was detected by CCK-8 assay and EdU staining.Cell migration and invasion were detected by scratch and Transwell as-says.The expressions of β-catenin,c-Myc,cyclin D1,MMP-7 and MMP-9 were detected by Western blot.The tumor formation and tumor volume in each group were assessed using nude mouse xenograft tumor model,while the expressions of MMP-9 and Ki67 in tumor tissue were examined by immunohistochemistry.Results The expression of CXCR3 was up-regulated in HB tissue(P<0.01).Compared to the Con-shR-NA group,the viability,proliferation,migration and invasion of Huh-6 and HepT1 cells in the CXCR3-shR-NA1 and CXCR3-shRNA2 groups were reduced(P<0.01),the expressions of the Wnt/β-catenin signaling pathway related proteins were attenuated(P<0.01),the tumor grew slowly and the volume was significantly reduced(P<0.01),and the expressions of MMP-9 and Ki67 in tumor tissue decreased(P<0.01).Con-clusions Downregulation of CXCR3 hinders the pro-liferation and migration of HB cells,potentially as-cribed to the attenuation of Wnt/β-catenin signaling regulation.
9.Investigation of tick species and potential pathogenic ricks in certain areas of Wuwei City,Gansu Province
Rui-Shan LI ; Zhen HE ; Xiang YUAN ; Shi-Wei SUN ; Yi-Wen LIU ; Wen-Kai ZHANG ; Lin ZHANG ; Yu-Hua WANG ; Zhen-Hua LU ; Zhao-Hua JI ; Zhong-Jun SHAO
Chinese Journal of Zoonoses 2024;40(4):328-333
To understand the distribution of ticks in the Wuwei Region,enrich tick species data,and provide a basis for the prevention of tick-borne diseases,tick were collected using flagging and tick-picking methods during the highest activity period from April to September in 2021 and 2022 in the mountainous areas of Wuwei City.The ticks were identified based on morpho-logical and molecular biological characteristics,and characteristic sequences were obtained.A systematic evolutionary tree was constructed using the neighbor-joining method in MEGA 11.0 software.In total,7 342 ticks collected in Wuwei,which be-longed to 5 species from 4 genera with in the Ixodidae family,which included Dermacentor nuttalli,Hyalomma asiaticum,Ixodes canisuga,Haemaphysalis longicornis and Haema-physalis danieli.Ticks of the same species clustered together into the same branch of an evolutionary tree.In the Wuwei Re-gion,five common tick species are found across various habi-tats,with each habitat featuring different distributions of tick species and populations.The Dermacentor nuttalli is the dom-inant tick species in this area.
10.Development of microsatellite markers and analysis of genetic characteristics of laboratory Apodemus peninsulae population
Qing ZHANG ; Xiwen ZHANG ; Song HE ; Bao YUAN ; Jian CHEN ; Wenzhi REN ; Fushi QUAN ; Jinping HU ; Yu DING
Acta Laboratorium Animalis Scientia Sinica 2024;32(4):468-476
Objective Polymorphic microsatellite markers developed for Apodemus peninsulae can enrich its genetic data and lay a foundation for genetic quality control and gene mapping.Methods Microsatellite loci were screened based on the genome sequence of Apodemus peninsulae,and microsatellite primers were identified.The genetic diversity of the population was analyzed by multiplex PCR.Results Thirty microsatellite markers were successfully developed and evaluated using 60 samples of Apodemus peninsulae.A total of 152 alleles were detected,with an average of 5.067 alleles per locus.The average observed heterozygosity was 0.592.The average Shannon index was 1.265.The average polymorphism information content was 0.598.Conclusions Based on the microsatellite loci developed in this study,the genetic diversity of Apodemus peninsulae can be effectively analyzed,laying a foundation for establishing genetic quality standards and detection method.

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