1.Atorvastatin inhibits orthodontic tooth movement in rats by promoting periodontal bone formation
Xinyi SONG ; Siqi DING ; Yuhe CHENG ; Xiaoyu LIU ; Tingting WU
Acta Universitatis Medicinalis Anhui 2026;61(2):344-354
ObjectiveTo investigate the effects of atorvastatin (ATV) on the proliferation and differentiation of rat bone marrow mesenchymal stem cells (BMSCs), periodontal ligament stem cells (PDLSCs), and dental pulp stem cells (DPSCs) in vitro, and to validate the regulatory effect of ATV on periodontal bone formation and tooth movement using a rat orthodontic tooth movement (OTM) model. MethodsThe effects of ATV on the proliferation and osteogenic/odontogenic differentiation of rat BMSCs, PDLSCs, and DPSCs were assessed in vitro. CCK-8 assay was used to detect the proliferation of the three types of cells. Alkaline phosphatase (ALP) staining and Alizarin Red staining were employed to evaluate osteogenic differentiation capacity. Western blot was used to detect the expression of osteogenesis-related proteins [collagen type I (COL-I), Runt-related transcription factor 2 (Runx2), bone morphogenetic protein-2 (BMP-2), osteocalcin (OCN)] and the odontogenesis-related protein dentin sialophosphoprotein (DSPP) in BMSCs, PDLSCs and DPSCs. An OTM rat model was established, with rats randomly assigned to an ATV gavage group and a control group. The ATV gavage group received daily oral administration of ATV at a dose of 20 mg/kg, while the control group received an equal volume of solvent by gavage. Tooth movement distance was measured via Micro-CT on days 7, 14, and 21. Histomorphology of periodontal tissues was observed using Hematoxylin and Eosin (HE) staining and Masson staining. The gene and protein expression levels of osteogenic markers (BMP-2, Runx2, OCN) on the tension side of the first molar were detected by qRT-PCR and immunohistochemistry, respectively. ResultsATV at concentrations of 1×10⁻⁶ mol/L and 1×10⁻⁷ mol/L significantly promoted the proliferation and osteogenic/odontogenic differentiation of BMSCs, PDLSCs, and DPSCs, manifested as enhanced ALP activity, increased mineralized nodule formation, and up-regulated expression of osteogenic/odontogenic proteins COL-I, Runx2, BMP-2, OCN, and DSPP (P<0.001). In the OTM model, compared with the control group, the ATV gavage group showed a significant reduction in tooth movement distance (P<0.05), enhanced osteogenic activity in periodontal tissues, and significantly increased gene (P<0.001) and protein (P<0.05) expression of BMP-2, Runx2, and OCN on the tension side of the first molar. ConclusionATV enhances periodontal osteogenesis by promoting osteogenic/dentinogenic differentiation, thus inhibiting tooth movement.
2.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.
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.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.
5.Construction and application of clinical inapplicability evaluation system for instructions of oral Chinese patent medicines containing toxic decoction pieces
He TANG ; Longlong TANG ; Xiaoyu JU ; Youquan TANG ; Zhihua WANG ; Jie CHENG
China Pharmacy 2026;37(11):1398-1402
OBJECTIVE To construct a clinical inapplicability evaluation system for the instructions of oral Chinese patent medicines containing toxic decoction pieces, so as to provide references for the revision and improvement of such drug instructions and the formulation of instructions for new drugs. METHODS The initial indicator framework was determined based on policy documents and literature related to instruction registration and revision. Two rounds of Delphi consultation were conducted among 25 experts to refine and optimize the indicator system. The analytic hierarchy process was employed to construct judgment matrices and obtain indicator weights. The comprehensive weights were converted into a 100-point scale to evaluate 11 instructions of oral Chinese patent medicines containing toxic decoction pieces from the medical institution of the research team. RESULTS The average questionnaire recovery rate of the two rounds of consultation was 96%. The expert authority coefficients were 0.87 and 0.88, respectively, and the Kendall’s W was statistically significant ( P <0.001). The final evaluation system comprised 4 first-level indicators (defect of toxicity identification, defect of dosage information, defect of risk warning, and defect of information guidance) and 24 second-level indicators (e.g., failure to label toxic decoction pieces in 【warnings】, failure to indicate all decoction piece compositions, absence of medication course specifications, etc.). The total scores of the 11 oral Chinese patent medicine instructions ranged from 15.50 to 50.87 points. The main clinical inapplicability issues included the absence of medication course specifications and the failure to provide warnings in items such as 【precautions】 for decoction pieces involving the “eighteen incompatibilities and nineteen mutual antagonisms”. CONCLUSIONS The constructed indicator system can meet the requirements for evaluating the clinical inapplicability of instructions for oral Chinese patent medicines containing toxic decoction pieces. All evaluated instructions exhibited certain clinical applicability defects. Pharmaceutical manufacturers should revise the instructions in accordance with policy requirements and clinical needs.
6.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.
7.Extracellular vesicles secreted by adriamycin-resistant breast cancer cells promote the proliferation and migration of HUVEC and tumor angiogenesis
Ke XI ; Xiaoyu DING ; Cheng WANG ; Junjun WANG ; Chunni ZHANG
Chinese Journal of Clinical Laboratory Science 2025;43(9):673-679
Objective To investigate the regulatory effects and molecular mechanisms of extracellular vesicles(EVs)secreted by adri-amycin(ADR)-resistant breast cancer cells on vascular endothelial cells related to tumor microenvironment.Methods The ADR-sen-sitive breast cancer cell line(MCF-7)and its ADR-resistant counterpart(MCF-7-ADR)were established in vitro.Then,the EVs were isolated from the supernatant of cell culture using a commercial kit.The fluorescence labeling and tracking technology using PKH67 was used to validate the internalization of EVs by human umbilical vein endothelial cell(HUVEC).The effects of EVs on the proliferation,migration,and angiogenesis of HUVEC were assessed by the colony formation,scratch wound healing,and tube formation assays,re-spectively.The expression level of CD31 protein was detected by Western blot,and the levels of vascular endothelial growth factor(VEGF)in cell supernatant were determined by ELISA.The microRNA(miRNA)sequencing technology was utilized to identify the differentially expressed miRNAs in EVs secreted by ADR-resistant cells.Results Compared with the ADR-sensitive strain,the EVs secreted by the ADR-resistant strain significantly enhanced the proliferation(colony number increased by 38.7%,P=0.011),migra-tion(scratch healing rate improved by 42.3%,P=0.004),and tube formation ability(tube formation rates increased by 1.8 times and 2.3 times at 4 h and 16 h,respectively,P=0.044 and 0.010)of HUVEC.Western blot analysis showed that the expression level of CD31 in the EVs secreted by the ADR-resistant strain increased by 1.85 times compared with the ADR-sensitive strain(P=0.039).The results of ELISA showed that the expression level of VEGF increased by 2.12 times(P=0.012).The miRNA sequencing identified a differentially expressed miRNA profile.Conclusion The ADR-resistant breast cancer cells significantly enhance the proliferation,migration,and angiogenesis of vascular endothelial cells by secreting EVs rich in specific miRNA,and its mechanism may be related to the up-regulation of CD31/VEGF protein levels mediated by EVs,suggesting that the drug-resistant cells reshaping the tumor vascular microenvironment through EVs may become a new therapeutic target of chemotherapy resistance in breast cancer.
8.Imaging features of Langerhans cell histiocytosis of long bones in children
Zhen ZHAO ; Cheng ZHANG ; Chang WANG ; Xiaoyu WANG ; Chuangao YIN
Journal of Practical Radiology 2025;41(4):642-645
Objective To investigate the imaging features of Langerhans cell histiocytosis(LCH)in the long bones of the limbs in children.Methods The clinical and imaging data of 23 children with long bones of the limbs were analyzed retrospectively.X-ray examinations were performed in 21 cases,CT scans in 16 cases,and MRI scans in 19 cases.Results The lesions were located in femur in 14 cases,tibia in 3 cases,fibula in 2 cases,humerus in 1 case,ulna in 2 cases,and both tibia and fibula in 1 case.Lesions were found in the diaphysis in 16 cases and the metaphysis in 7 cases(involving the epiphysis in 2 cases).Bone destruction appeared as oval,irregular,or eccentric shapes,with clear boundaries in 17 cases,blurred boundaries in 6 cases,and sclerosis in 6 cases.The average CT value was(48.27±8.20)HU,with"gear-like"changes in the axial view in 10 cases."Sleeve-like"periosteal reaction was observed in 14 cases,localized periosteal reaction in 5 cases,and no periosteal reaction in 4 cases.The lesions showed iso-or slightly hypointense signals on T1 WI,hyperintense signals on T2 WI,and hyperintense signals on diffusion weighted imaging(DWI),with an average apparent diffusion coefficient(ADC)value of(1.26±0.17)×10-3 mm2/s.Soft tissue masses were found in 7 cases.After enhancement,moderate to marked enhancement was observed in 9 cases,with lace-like enhancement in 6 cases.Among the 17 cases followed up,13 cases returned to normal or had only residual bone cortical thickening,3 cases showed a reduction in lesion size,and 1 case died.Conclusion The imaging features of LCH in the long bones in children have certain characteristics,but can still be easily confused with infections or malignant bone tumors.A comprehensive analysis combining clinical and imaging features is necessary to improve diagnostic accuracy.
9.Extracellular vesicles secreted by adriamycin-resistant breast cancer cells promote the proliferation and migration of HUVEC and tumor angiogenesis
Ke XI ; Xiaoyu DING ; Cheng WANG ; Junjun WANG ; Chunni ZHANG
Chinese Journal of Clinical Laboratory Science 2025;43(9):673-679
Objective To investigate the regulatory effects and molecular mechanisms of extracellular vesicles(EVs)secreted by adri-amycin(ADR)-resistant breast cancer cells on vascular endothelial cells related to tumor microenvironment.Methods The ADR-sen-sitive breast cancer cell line(MCF-7)and its ADR-resistant counterpart(MCF-7-ADR)were established in vitro.Then,the EVs were isolated from the supernatant of cell culture using a commercial kit.The fluorescence labeling and tracking technology using PKH67 was used to validate the internalization of EVs by human umbilical vein endothelial cell(HUVEC).The effects of EVs on the proliferation,migration,and angiogenesis of HUVEC were assessed by the colony formation,scratch wound healing,and tube formation assays,re-spectively.The expression level of CD31 protein was detected by Western blot,and the levels of vascular endothelial growth factor(VEGF)in cell supernatant were determined by ELISA.The microRNA(miRNA)sequencing technology was utilized to identify the differentially expressed miRNAs in EVs secreted by ADR-resistant cells.Results Compared with the ADR-sensitive strain,the EVs secreted by the ADR-resistant strain significantly enhanced the proliferation(colony number increased by 38.7%,P=0.011),migra-tion(scratch healing rate improved by 42.3%,P=0.004),and tube formation ability(tube formation rates increased by 1.8 times and 2.3 times at 4 h and 16 h,respectively,P=0.044 and 0.010)of HUVEC.Western blot analysis showed that the expression level of CD31 in the EVs secreted by the ADR-resistant strain increased by 1.85 times compared with the ADR-sensitive strain(P=0.039).The results of ELISA showed that the expression level of VEGF increased by 2.12 times(P=0.012).The miRNA sequencing identified a differentially expressed miRNA profile.Conclusion The ADR-resistant breast cancer cells significantly enhance the proliferation,migration,and angiogenesis of vascular endothelial cells by secreting EVs rich in specific miRNA,and its mechanism may be related to the up-regulation of CD31/VEGF protein levels mediated by EVs,suggesting that the drug-resistant cells reshaping the tumor vascular microenvironment through EVs may become a new therapeutic target of chemotherapy resistance in breast cancer.
10.Strategies for Weight Management in Children and Adolescents:Self-Regulated Nutrition,Family-School Collaboration,and Social Environment Optimization
Xiaoyu WANG ; Yujie XU ; Jingyuan XIONG ; Guo CHENG
Journal of Sichuan University (Medical Sciences) 2025;56(4):977-983
The prevalence of obesity among children and adolescents in China is rising at an alarming rate,with projections indicating that the national obesity rate will reach 15.1%by 2030.This trend not only affects physical development during childhood and adolescence but also has long-term implications for adult health outcomes.In response,the Chinese government has prioritized improving nutrition and preventing chronic diseases among children and adolescents.Facing this public health challenge,governments at all levels have implemented measures such as disseminating knowledge and skills for preventing overweight and obesity and improving sports facilities to foster a supportive environment conducive to the prevention of overweight and obesity.Schools contribute by improving food offerings and ensuring adequate time for physical activity when children attend school.Families play a critical role,with parents and caregivers guiding children toward healthy eating habits and monitoring their growth and weight.Children and adolescents are encouraged to adopt balanced diets,actively participate in physical exercise,and maintain psychological well-being to develop a positive and healthy mindset that supports their growth and long-term health.Despite these efforts,challenges persist,including unequal access to health resources and increasingly obesogenic environments.Future efforts should focus on utilizing digital technologies to develop precision intervention instruments and on formulating integrated strategies that engage society,schools,families,and individuals through policy guidance.Such comprehensive approaches aim to reduce the risks of obesity and its complications,enhance physical and mental health,and reduce healthcare and socioeconomic burdens.

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