1.Ershen Zhenwu Decoction Treats Chronic Heart Failure by Regulating miR-423-5p/Smad7/TGF-β1/Smads Axis and Myocardial Fibrosis Indicators
Lan GE ; Zhenpeng ZHU ; Xinyue WANG ; Dan CHENG ; Yulong LIU ; Maomao ZHANG ; Xiaoyu CHENG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):157-165
ObjectiveTo investigate the clinical effect of Ershen Zhenwu Decoction on chronic heart failure (CHF) due to heart-kidney Yang deficiency and blood stasis and its regulatory effects on miR-423-5p/Smad7/transforming growth factor-β1 (TGF-β1)/Smads axis and myocardial fibrosis indicators. MethodsOne hundred and fourteen patients with heart failure with reduced ejection fraction (HFrEF) and heart failure with mildly reduced ejection fraction (HFmrEF) were randomly allocated into a control group and an observation group. The control group was treated with dapagliflozin tablets, sacubitril-valsartan sodium tablets, metoprolol succinate, and spironolactone, and the observation group was treated with Ershen Zhenwu Decoction on the basis of the therapy in the control group. The course of treatment was 8 weeks in both groups. The 6-min walking distance, New York Heart Association (NYHA) heart function grade, Minnesota Living with Heart Failure Questionnaire (MLHFQ) score, N-terminal pro-B-type natriuretic peptide (NT-proBNP), angiotensin Ⅱ (Ang Ⅱ), left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVIDd), left ventricular end-systolic diameter (LVIDs), interventricular septum thickness at diastole (IVSd), left ventricular end-diastolic posterior wall thickness (LVPWd), left ventricular shortening fraction (FS), miR-423-5p, Smad7, Smad2, Smad3, Smad4, TGF-β1, Ang Ⅱ, type Ⅰ collagen (Col Ⅰ), type Ⅲ collagen (Col Ⅲ), mRNA levels of fibronectin (Fn) and α-smooth muscle actin (α-SMA) in the myocardial tissue were observed before and after treatment in both groups to evaluate the efficacy of cardiac function and drug safety. ResultsAfter treatment, both groups showed declined levels of NT-proBNP, Ang Ⅱ, miR-423-5p, Smad2, Smad3, Smad4, TGF-β1, Col Ⅰ, Col Ⅲ, and mRNA levels of Fn and α-SMA (P0.05), and the levels of the indicators above were lower in the observation group than in the control group (P0.05). After treatment, the Smad7 level increased obviously in both groups (P0.05) and was higher in the observation group than in the control group (P0.05). After treatment, both groups showed decreased MLHFQ scores and increased 6-min walking distance (P0.05), and the observation group had lower MLHFQ score and longer 6-min walking distance than the control group (P0.05). After treatment, the control group showed increased LVEF and FS (P0.05) and the observation group showcased decreased LVIDd and LVIDs and increased LVEF and FS (P0.05). Moreover, the observation group had lower LVIDd and LVIDs (P0.05) and higher LVEF and FS (P0.05) than the control group. The total response rate of cardiac function in the observation group was 90.38% (47/52), which was higher than that (70.59%, 36/51) in the control group (P0.05). No adverse reactions associated with Ershen Zhenwu Decoction were observed during the study period. ConclusionErshen Zhenwu Decoction can improve the cardiac function, exercise tolerance, and quality of life, regulate neuroendocrine factors, and slow down/reverse myocardial remodeling in the patients with HFrEF and HFmrEF (syndrome of heart-kidney Yang deficiency and blood stasis by regulating the miR-423-5p/Smad7/TGF-β1/Smads axis, inhibiting α-SMA and Fn expression, and alleviating myocardial fibrosis. It is worthy of further study.
2.Analysis of Animal Models of Dry Age-related Macular Degeneration Based on Clinical Disease-syndrome Characteristics of Traditional Chinese and Western Medicine
Xiaoyu LI ; Lina LIANG ; Yun GAO ; Jiahao LI ; Jianying YANG ; Xiaoshan ZHANG ; Honghao BI ; Menglu MIAO ; Huiyi GUO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):191-197
ObjectiveAge-related macular degeneration (AMD) is one of the leading causes of low vision and blindness in people over 50 years old, and dry AMD (dAMD) is one type for which there is currently no clear treatment. On the basis of the diagnosis and clinical characteristics of dAMD in traditional Chinese and Western medicine, this paper evaluated the fitting degrees of existing animal models of dAMD with clinical characteristics according to the evaluation methods of animal models, and put forward suggestions and prospects. MethodsLiterature on animal models of dAMD was searched against database, and the characteristics of the models were assigned according to the diagnosis criteria of diseases and syndromes of traditional Chinese and Western medicine, and the fitting degrees of the models with clinical characteristics were analyzed and evaluated. ResultsAt present, the animal models of dAMD are mainly established targeting complement factors, chemokines, oxidative damage, lipid/glucose metabolism, and natural strains. Most of the models can simulate the major pathological changes of dAMD, showing the fitting degree of 25%-50% with clinical characteristics in Western medicine. However, the evaluation of traditional Chinese medicine (TCM) syndromes, especially the evaluation of secondary syndromes, is missing, and the models present low fitting degrees with the clinical characteristics in TCM. ConclusionExisting animal models of dAMD are mostly established under the guidance of Western diagnostic standards, which reproduce the main disease characteristics of Western medicine and lack observation of TCM syndromes. Future studies can pay attention to the intervention factors and evaluation systems of spleen deficiency Qi deficiency and liver-kidney Yin deficiency syndrome and build the animal model of dAMD with integration of disease and syndrome based on clinical characteristics of traditional Chinese and Western medicine.
3.Ershen Zhenwu Decoction Treats Chronic Heart Failure by Regulating miR-423-5p/Smad7/TGF-β1/Smads Axis and Myocardial Fibrosis Indicators
Lan GE ; Zhenpeng ZHU ; Xinyue WANG ; Dan CHENG ; Yulong LIU ; Maomao ZHANG ; Xiaoyu CHENG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):157-165
ObjectiveTo investigate the clinical effect of Ershen Zhenwu Decoction on chronic heart failure (CHF) due to heart-kidney Yang deficiency and blood stasis and its regulatory effects on miR-423-5p/Smad7/transforming growth factor-β1 (TGF-β1)/Smads axis and myocardial fibrosis indicators. MethodsOne hundred and fourteen patients with heart failure with reduced ejection fraction (HFrEF) and heart failure with mildly reduced ejection fraction (HFmrEF) were randomly allocated into a control group and an observation group. The control group was treated with dapagliflozin tablets, sacubitril-valsartan sodium tablets, metoprolol succinate, and spironolactone, and the observation group was treated with Ershen Zhenwu Decoction on the basis of the therapy in the control group. The course of treatment was 8 weeks in both groups. The 6-min walking distance, New York Heart Association (NYHA) heart function grade, Minnesota Living with Heart Failure Questionnaire (MLHFQ) score, N-terminal pro-B-type natriuretic peptide (NT-proBNP), angiotensin Ⅱ (Ang Ⅱ), left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVIDd), left ventricular end-systolic diameter (LVIDs), interventricular septum thickness at diastole (IVSd), left ventricular end-diastolic posterior wall thickness (LVPWd), left ventricular shortening fraction (FS), miR-423-5p, Smad7, Smad2, Smad3, Smad4, TGF-β1, Ang Ⅱ, type Ⅰ collagen (Col Ⅰ), type Ⅲ collagen (Col Ⅲ), mRNA levels of fibronectin (Fn) and α-smooth muscle actin (α-SMA) in the myocardial tissue were observed before and after treatment in both groups to evaluate the efficacy of cardiac function and drug safety. ResultsAfter treatment, both groups showed declined levels of NT-proBNP, Ang Ⅱ, miR-423-5p, Smad2, Smad3, Smad4, TGF-β1, Col Ⅰ, Col Ⅲ, and mRNA levels of Fn and α-SMA (P0.05), and the levels of the indicators above were lower in the observation group than in the control group (P0.05). After treatment, the Smad7 level increased obviously in both groups (P0.05) and was higher in the observation group than in the control group (P0.05). After treatment, both groups showed decreased MLHFQ scores and increased 6-min walking distance (P0.05), and the observation group had lower MLHFQ score and longer 6-min walking distance than the control group (P0.05). After treatment, the control group showed increased LVEF and FS (P0.05) and the observation group showcased decreased LVIDd and LVIDs and increased LVEF and FS (P0.05). Moreover, the observation group had lower LVIDd and LVIDs (P0.05) and higher LVEF and FS (P0.05) than the control group. The total response rate of cardiac function in the observation group was 90.38% (47/52), which was higher than that (70.59%, 36/51) in the control group (P0.05). No adverse reactions associated with Ershen Zhenwu Decoction were observed during the study period. ConclusionErshen Zhenwu Decoction can improve the cardiac function, exercise tolerance, and quality of life, regulate neuroendocrine factors, and slow down/reverse myocardial remodeling in the patients with HFrEF and HFmrEF (syndrome of heart-kidney Yang deficiency and blood stasis by regulating the miR-423-5p/Smad7/TGF-β1/Smads axis, inhibiting α-SMA and Fn expression, and alleviating myocardial fibrosis. It is worthy of further study.
4.Analysis of Animal Models of Dry Age-related Macular Degeneration Based on Clinical Disease-syndrome Characteristics of Traditional Chinese and Western Medicine
Xiaoyu LI ; Lina LIANG ; Yun GAO ; Jiahao LI ; Jianying YANG ; Xiaoshan ZHANG ; Honghao BI ; Menglu MIAO ; Huiyi GUO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):191-197
ObjectiveAge-related macular degeneration (AMD) is one of the leading causes of low vision and blindness in people over 50 years old, and dry AMD (dAMD) is one type for which there is currently no clear treatment. On the basis of the diagnosis and clinical characteristics of dAMD in traditional Chinese and Western medicine, this paper evaluated the fitting degrees of existing animal models of dAMD with clinical characteristics according to the evaluation methods of animal models, and put forward suggestions and prospects. MethodsLiterature on animal models of dAMD was searched against database, and the characteristics of the models were assigned according to the diagnosis criteria of diseases and syndromes of traditional Chinese and Western medicine, and the fitting degrees of the models with clinical characteristics were analyzed and evaluated. ResultsAt present, the animal models of dAMD are mainly established targeting complement factors, chemokines, oxidative damage, lipid/glucose metabolism, and natural strains. Most of the models can simulate the major pathological changes of dAMD, showing the fitting degree of 25%-50% with clinical characteristics in Western medicine. However, the evaluation of traditional Chinese medicine (TCM) syndromes, especially the evaluation of secondary syndromes, is missing, and the models present low fitting degrees with the clinical characteristics in TCM. ConclusionExisting animal models of dAMD are mostly established under the guidance of Western diagnostic standards, which reproduce the main disease characteristics of Western medicine and lack observation of TCM syndromes. Future studies can pay attention to the intervention factors and evaluation systems of spleen deficiency Qi deficiency and liver-kidney Yin deficiency syndrome and build the animal model of dAMD with integration of disease and syndrome based on clinical characteristics of traditional Chinese and Western medicine.
5.Effect and Mechanisms of Luteolin on Gout
Jinlai CHENG ; Xiaoyu ZHANG ; Yuyan XU ; Huajing WANG ; Yuqing TAN ; Feng SUI ; Miyi YANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(1):140-149
ObjectiveTo integrate network pharmacology prediction with multi-level experimental verification methods, and to explore in depth the therapeutic efficacy and potential mechanism of luteolin in treating gout. MethodsDatabases were used to obtain potential pharmacodynamic targets of luteolin. Protein-protein interaction (PPI) network construction and network pharmacology analysis techniques were used to screen key core targets of luteolin in gout treatment. Further biological function enrichment analysis and signaling pathway analysis were performed on these targets. Molecular docking simulation was used to calculate the binding energy between luteolin and potential core targets, clarifying the strength of their interactions. In the in vivo experiment for hyperuricemia, 48 mice were randomly divided into a blank group, a model group, an allopurinol group (5 mg·kg-1), and low-dose (10 mg·kg-1), medium-dose (30 mg·kg-1), and high-dose (90 mg·kg-1) luteolin groups. For the first three days, the blank and model groups were gavaged with an equal volume of normal saline, while the allopurinol group and luteolin groups were gavaged with corresponding drugs. From day 4 onwards, modeling was performed by intraperitoneal injection at 12:00 daily (normal saline for the blank group, and oxonic acid potassium-hypoxanthine mixture for other groups, with 300 mg·kg-1 for each group). Gavage intervention was administered at 18:00 daily (normal saline for the blank/model groups, and corresponding drugs for the treatment groups) until day 7. After sampling, levels of serum uric acid (UA), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were measured. Levels of xanthine oxidase (XO) in the liver and kidney, ATP-binding cassette transporter G2 (ABCG2) and malondialdehyde (MDA) in the kidney, and superoxide dismutase (SOD) in the liver were determined. Renal HE staining was also performed. In the pharmacodynamic study of gouty arthritis, 36 rats were randomly divided into a blank group, a model group, a colchicine group (0.315 mg·kg-1), and low-dose (7 mg·kg-1), medium-dose (21 mg·kg-1), and high-dose (63 mg·kg-1) luteolin groups. The model was established by vertically injecting 100 µL of 25 g·L-1 monosodium urate suspension into the posterior lateral aspect of the right ankle joint (the blank group was injected with an equal volume of normal saline), with repeated injections every two days for reinforcement. From day 2 after modeling, daily gavage administration was performed (normal saline for the blank/model groups, and corresponding drugs for the treatment groups) for a total of 16 days. During the experiment, ankle swelling and pain threshold were measured regularly. After sampling, levels of serum tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) were determined. Ankle joints were subjected to HE, Masson, and safranin O-fast green staining, and HE staining was also performed on ankle synovial tissue and various organs. Western blot was used to determine the expression levels of key proteins in gout-related signaling pathways. ResultsNetwork pharmacology analysis predicted that luteolin may regulate over 20 core targets, such as XO, ABCG2, nuclear factor erythroid 2-related factor 2 (Nrf2), and SOD, through acting on signaling pathways including NF-κB, phosphoinositide 3-kinase/protein kinase B (PI3K/Akt), and ABC transporters, thereby affecting uric acid metabolism and inflammatory responses. In the hyperuricemia model, compared with the blank group, the model group showed significantly increased serum UA level, liver and kidney XO activity, renal ABCG2 expression, and liver SOD activity (P<0.01). Compared with the model group, the high-dose luteolin group significantly reduced serum UA level (P<0.01), inhibited liver and kidney XO activity (P<0.01), and significantly increased renal ABCG2 expression and liver SOD activity (P<0.01), effectively alleviating renal oxidative stress damage and improving renal histopathological status. In the gouty arthritis model, compared with the blank group, the model group showed significant ankle swelling, decreased pain threshold, and significantly increased levels of IL-6, IL-1β, and TNF-α in serum and synovial tissue (P<0.01). The high-dose luteolin group significantly reduced ankle swelling, prolonged hot plate pain threshold, effectively decreased the levels of the above inflammatory factors in serum and synovial tissue (P<0.01), and significantly improved ankle pathological damage, showing good analgesic and anti-inflammatory effects. Western blot results further confirmed that luteolin significantly upregulated Nrf2 protein expression and downregulated XO and nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3) expression in animals. ConclusionLuteolin can improve symptoms of hyperuricemia and gouty arthritis, and its potential mechanism may be related to inhibiting XO activity, increasing ABCG2 and SOD levels, and regulating Nrf2-mediated oxidative stress-related pathways.
6.Intervention of Signaling Pathways Related to Ulcerative Colitis with Traditional Chinese Medicine: A Review
Hao WANG ; Jiali DING ; Guangjun SUN ; Xiaoyu ZHANG ; Aizhen LIN
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(7):331-340
Ulcerative colitis (UC) is a common digestive disease characterized by recurrence and remission alternation,which seriously affects the life quality and physical and mental health of patients. The pathogenesis of UC is complex,and studies have shown that the occurrence and development of UC are closely related to the transduction of multiple signaling pathways. The current western medicine treatment has many problems,such as single action target,more adverse reactions,poor patient tolerance,and easy recurrence after stopping the medicine. Traditional Chinese medicine has the advantages such as multi-targets,multi-pathways, and fewer adverse reactions, elucidating that the action mechanism of traditional Chinese medicine in the treatment of UC is the focus of current research. Therefore, this paper conducted a systematic review on how traditional Chinese medicine exerts therapeutic effects by regulating the signaling pathways related to UC in recent years,and it was found that traditional Chinese medicine can regulate nuclear factor-κB (NF-κB),adenylate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR),Janus tyrosine protein kinase (JAK)/signal transducer and activator of transcription (STAT),phosphatidylinositol 3-kinase (PI3K) /protein kinase B (Akt),NOD-like receptor thermoprotein structural domain-related protein 3 (NLRP3)/cysteine protease-1 (Caspase-1),nuclear respiratory factor 2 (Nrf2)/heme oxygenase-1 (HO-1), and several other pathways,thereby inhibiting oxidative stress and cellular pyroptosis,regulating the Tregs/Th17 cellular balance, promoting autophagic response and M2-type macrophage polarization,restoring the diversity and abundance of intestinal flora,promoting the repair of intestinal mucosal barrier function,and alleviating the inflammatory damage of UC colonic tissues. The holistic concept and evidence-based treatment of traditional Chinese medicine were combined with the modern molecular mechanism research of traditional Chinese medicine, and the traditional Chinese medicine combinations with different mechanisms, following regulation, were formulated into compound formulas or pairs of medicines according to the pattern of evidence. It is expected to achieve better therapeutic efficacy and to provide ideas and references for the modification of classic compound formulae of traditional Chinese medicine in UC treatment and clinical translation.
7.Mechanisms of Traditional Chinese Medicine in Treatment of Ulcerative Colitis Based on AMPK Signaling Pathway: A Review
Keqiu YAN ; Xiaoyu ZHANG ; Yifan CAI ; Wenjie XIAO ; Xinkun BAO ; Guangjun SUN ; Aizhen LIN
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(7):341-351
Ulcerative colitis (UC), a chronic relapsing inflammatory bowel disease, involves multifaceted pathological mechanisms such as intestinal barrier dysfunction, immune dysregulation, and oxidative stress. Current therapeutic strategies remain limited in efficacy and safety. In recent years, the adenosine monophosphate-activated protein kinase (AMPK) signaling pathway has emerged as a pivotal therapeutic target for UC due to its central role in energy metabolism, inflammatory regulation, and intestinal homeostasis. This article systematically reviewed the mechanisms by which traditional Chinese medicine (TCM) prevented and treated UC through the regulation of the AMPK signaling pathway, with a focus on elucidating AMPK's multidimensional regulatory network in inflammatory signaling crosstalk, alleviating oxidative stress, restoring intestinal immune balance, repairing the intestinal barrier, and modulating gut microbiota. Leveraging its unique advantages of multi-target engagement and low toxicity, TCM demonstrates promising potential in UC treatment and has become a focal area of research. By systematically summarizing and synthesizing the existing literature on TCM-mediated AMPK pathway modulation in UC, this review aims to provide a theoretical foundation for advancing mechanistic research and clinical interventions in UC.
8.Effect of lncRNA-TNFRSF13C on hypoxia-inducible factor 1alpha in periodontal cells by modulation of miR-1246
Jing BAI ; Xue ZHANG ; Yan REN ; Yuehui LI ; Xiaoyu TIAN
Chinese Journal of Tissue Engineering Research 2025;29(5):928-935
BACKGROUND:LncRNA-TNFRSF13C,an important factor in B cell development and function,is expressed in periodontal tissues of patients with periodontitis,but the specific mechanism is still unclear. OBJECTIVE:To investigate the mechanism of lncRNA-TNFRSF13C regulating miR-1246 on hypoxia-inducible factor 1α in periodontal cells. METHODS:Human periodontal ligament cells(hPDLCs)were treated with lipopolysaccharide and divided into group A(hPDLCs cell lines without transfection),group B(hPDLCs cell lines transfected with TNFRSF13C NC-siRNA),group C(hPDLCs cell lines transfected with TNFRSF13C-siRNA),group D(hPDLCs cell line transfected with miR-1246 mimics),group E(hPDLCs cell line transfected with miR-1246 siRNA),group F(hPDLCs cell line transfected with TNFRSF13C-siRNA+miR-1246 mimics),and group G(hPDLCs cell line transfected with TNFRSF13C-siRNA+miR-1246 siRNA).The relative expression of lncRNA-TNFRSF13C and miR-1246 in each group was detected by qRT-PCR.Cell counting kit-8 assay was used to detect cell viability.Apoptosis was detected by flow cytometry.Expression of hypoxia-inducible factor 1α and vascular endothelial growth factor proteins was detected by western blot.The correlation between lncRNA-TNFRSF13C and miR-1246 was analyzed by Pearson,and the targeting relationship was analyzed by dual-luciferase reporter assay. RESULTS AND CONCLUSION:There was no significant difference in human periodontal ligament cell activity,apoptosis rate and protein indexes between groups A and B(P>0.05).Compared with group B,hPDLCS cell activity in group C was increased,and apoptosis rate and the expression of hypoxia-inducible factor 1α and vascular endothelial growth factor proteins were decreased(P<0.05).Compared with group C,hPDLCS cell activity in group D was decreased,and apoptosis rate and the expression of hypoxia-inducible factor 1α and vascular endothelial growth factor proteins were increased(P<0.05).Compared with group D,the cell activity of group E was increased(P<0.05).The cell activity in group F was lower than that in group E,and the apoptosis rate was reduced in both groups E and F(P<0.05).Compared with group F,the cell activity of group G was increased,and the apoptosis rate and the expression of hypoxia-inducible factor 1α and vascular endothelial growth factor were decreased(P<0.05).LncRNA-TNFRSF13C was positively correlated with miR-1246(P<0.05).Compared with the TNFRSF13C-siRNA group,the fluorescence activity of miR-1246-wt in the TNFRSF13C-NC group was reduced(P>0.05);compared with the miR-1246-NC group,the fluorescence activities of hypoxia-inducible factor 1α-wt and vascular endothelial growth factor-wt in the miR-1246 mimics group were increased(P<0.05).To conclude,down-regulation of lncRNA-TNFRSF13C can promote the activity of periodontal cells treated with lipopolysaccharide,reduce apoptosis,and inhibit hypoxia-inducible factor 1α and vascular endothelial growth factor.The mechanism is related to the regulation of miR-1246 activity.
9.Multiple applications of metal-organic framework materials in bone tissue engineering and orthopedic disease treatment
Yunxiang LIU ; Xiaoyu ZHANG ; Hao LI ; Rong ZHANG ; Liping LI ; Chongwei CHEN
Chinese Journal of Tissue Engineering Research 2025;29(10):2151-2161
BACKGROUND:Metal-organic frameworks exhibited great potential for bone tissue engineering and bone disease treatment because of its unique merits including tunable porosity,a large specific surface area,good biocompatibility,and easy structure modification. OBJECTIVE:To review the advancements,application,strengths,and weaknesses of metal-organic framework materials in bone repair,arthritis,bone infection,and bone tumors,offering guidance and strategies for future research. METHODS:Web of Science,PubMed,and CNKI databases were searched using Chinese and English keywords"metal-organic frameworks,MOFs,orthopedics,bone repair,bone regeneration,orthopaedic applications,bone tissue engineering,bone infection,arthritis,bone tumor,osteosarcoma"for related literature published from 2015 to 2023.Following initial screening based on inclusion and exclusion criteria,72 articles were finally included for review. RESULTS AND CONCLUSION:(1)During bone repair,metal ions of metal-organic frameworks can induce bone formation by activating specific signaling pathways,which include stimulating osteogenic gene expression,inhibiting osteoclasts,encouraging blood vessel formation,and speeding up bone mineralization.Hence,metal-organic frameworks with metals like calcium,strontium,cobalt,copper,and magnesium ions show significant potential in enhancing bone implant performance.(2)Metal-organic framework materials,especially zinc/cobalt-based metal-organic frameworks,exhibit enzyme-like activities and promote cartilage regeneration by scavenging reactive oxygen species.Compared with natural enzymes,it has the advantages of not easy inactivation and better stability.(3)Zinc-based metal-organic framework materials characterized with wide band gaps,efficient separation and migration of photogenerated carriers,and high stability,the enhancement of photocatalytic activity results from enhancing the excited electron-hole widely used for the eradication of bacteria and tumor cells.(4)Bimetallic metal-organic frameworks,the doping of additional metals,showed critical advantages in optimizing structural performance,such as zinc/magnesium-based metal-organic framework 74 offering increased stability for durable antibacterial activity,and the light absorption capacity and photocatalytic efficiency of tantalum/zirconium-based metal-organic framework greatly improved and thus enhancing the radiation therapy.(5)However,metal-organic framework materials still face challenges in clinical applications,such as the uncertainty of drug release,in vivo safety,and potential immune responses from long-term presence.
10.Effect of Folic Acid-modified Crebanine Polyethylene Glycol-polylactic Acid Hydroxyacetic Acid Copolymer Nanoparticles Combined with Ultrasonic Irradiation on Subcutaneous Tumor Growth of Liver Cancer in Mice
Rui PAN ; Junze TANG ; Hailiang ZHANG ; Kun YU ; Xiaoyu ZHAO ; Xin CHENG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(4):217-225
ObjectiveTo investigate the effect of folic acid-modified crebanine polyethylene glycol-polylactic acid hydroxyacetic acid copolymer(PEG-PLGA) nanoparticles(FA-Cre@PEG-PLGA NPs, hereinafter referred to as NPs) combined with ultrasonic irradiation on subcutaneous tumor of liver cancer in Kunming(KM) mice. MethodsEighty-four healthy male KM mice were utilized to establish a subcutaneous tumor model of mouse hepatocellular carcinoma with H22 cells, then mice were randomly divided into model group, placebo group, hydroxycamptothecin group(8 mg∙kg-1), low, medium and high dose crebanine raw material groups(2, 2.5, 3 mg∙kg-1, hereinafter referred to as the low, medium and high dose crebanine groups, respectively), low, medium and high dose NPs groups(2, 2.5, 3 mg∙kg-1), and low, medium and high dose NPs combined with ultrasonic irradiation groups(2, 2.5, 3 mg∙kg-1, hereinafter referred to as the low, medium and high dose combination groups, respectively). The corresponding doses of drugs were administered via tail vein injection, the model group received no treatment, while the placebo group was injected with an equivalent amount of normal saline. Dosing was conducted for a total of 10 times on alternate days. The body mass of the mice was monitored, and parameters such as body mass change rate, thymus index, spleen index, tumor volume, tumor weight, relative tumor growth rate(T/C), and tumor inhibition rate(TGI) were calculated. Pathological changes in liver and kidney tissues as well as the tumor were observed by hematoxylin-eosin(HE) staining. Additionally, the levels of aspartate aminotransferase(AST), alanine aminotransferase(ALT), blood urea nitrogen(BUN) and creatinine(CREA) in serum of mice were detected by biochemical method. Furthermore, the effect of ultrasound on the distribution of NPs in subcutaneous tumors of mouse hepatocellular carcinoma was observed by in vivo imaging technique. ResultsAmong different treatment methods, the combination of NPs and ultrasound irradiation had the best therapeutic effect. Compared with the model group, the body mass growth rates of mice in the medium and high combination groups decreased, while the thymus index and spleen index increased, but there was no statistically significant difference in serum AST, ALT, BUN and CREA levels, indicating that NPs combined with ultrasound irradiation had little effect on the normal physiological state of the body, oth groups had TGI>40% and T/C<60%, indicating a clear anti-tumor effect. Pathological analysis showed that compared with the NPs groups, the combination groups exhibited varying degrees of necrosis in tumor cells, accompanied by less damage to the liver and kidneys. In vivo imaging of small animals showed that compared with the high dose NPs group, the high dose combination group had stronger tumor targeting ability(P<0.01). ConclusionNPs combined with ultrasonic irradiation can not only effectively targeted the drug to the tumor site, inhibit the subcutaneous tumor growth of mouse liver cancer, but also decrease damage to liver and kidney tissues.

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