1.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.
2.Effects of clopidogrel on the pharmacokinetics and pharmacodynamics of ciprofol in rats
Ming LU ; Xiaoyu YIN ; Wenli LI ; Shan LI ; Xiangchen LI ; Zhiqing ZHANG
China Pharmacy 2025;36(2):179-184
OBJECTIVE To investigate the effects of clopidogrel on the pharmacokinetics and pharmacodynamics of ciprofol in rats. METHODS Eighteen male SD rats were randomly divided into control group, clopidogrel normal-dose group and clopidogrel high-dose group, with 6 rats in each group. Among them, rats in the normal-dose group and high-dose group were given 7.5 mg/kg and 15 mg/kg clopidogrel by gavage, respectively, and rats in the control group were given the same volume of 0.5% sodium carboxymethyl cellulose solution, once a day, for 14 consecutive days. Afterward, 2.4 mg/kg ciprofol was injected by tailvein and blood samples were collected from the inner canthus of the eye at 2, 4, 8, 12, 16, 20, 30, 45 and 60 min after the end of the administration. During this period, the duration of the loss of righting reflex (LORR) in rats was counted. After the proteins were precipitated by acetonitrile, the rat plasma sample was analyzed by LC-MS/MS using deuterated ciprofol as the internal standard, Symmetry C18 as the chromatographic column, and acetonitrile-0.01% ammonia solution containing 5 mmol/L ammonium acetate (gradient elution) as the mobile phase to detect the concentration of ciprofol in the plasma. The pharmacokinetic parameters in rats were calculated by using DAS 2.0 software. RESULTS Compared with control group, area under the drug concentration-time curve and mean residence time of ciprofol increased or prolonged significantly, while plasma clearance decreased significantly in clopidogrel normal-dose and high-dose groups; the duration of LORR in rats was prolonged by 19.5% and 23.9%, with statistical difference (P<0.05). However, there was no statistically significant difference in the pharmacokinetic parameters or LORR duration of ciprofol between the different dose groups of clopidogrel (P>0.05). CONCLUSIONS Clopidogrel could inhibit the metabolism of ciprofol in rats and prolong the duration of LORR.
3.Effects of clopidogrel on the pharmacokinetics and pharmacodynamics of ciprofol in rats
Ming LU ; Xiaoyu YIN ; Wenli LI ; Shan LI ; Xiangchen LI ; Zhiqing ZHANG
China Pharmacy 2025;36(2):179-184
OBJECTIVE To investigate the effects of clopidogrel on the pharmacokinetics and pharmacodynamics of ciprofol in rats. METHODS Eighteen male SD rats were randomly divided into control group, clopidogrel normal-dose group and clopidogrel high-dose group, with 6 rats in each group. Among them, rats in the normal-dose group and high-dose group were given 7.5 mg/kg and 15 mg/kg clopidogrel by gavage, respectively, and rats in the control group were given the same volume of 0.5% sodium carboxymethyl cellulose solution, once a day, for 14 consecutive days. Afterward, 2.4 mg/kg ciprofol was injected by tailvein and blood samples were collected from the inner canthus of the eye at 2, 4, 8, 12, 16, 20, 30, 45 and 60 min after the end of the administration. During this period, the duration of the loss of righting reflex (LORR) in rats was counted. After the proteins were precipitated by acetonitrile, the rat plasma sample was analyzed by LC-MS/MS using deuterated ciprofol as the internal standard, Symmetry C18 as the chromatographic column, and acetonitrile-0.01% ammonia solution containing 5 mmol/L ammonium acetate (gradient elution) as the mobile phase to detect the concentration of ciprofol in the plasma. The pharmacokinetic parameters in rats were calculated by using DAS 2.0 software. RESULTS Compared with control group, area under the drug concentration-time curve and mean residence time of ciprofol increased or prolonged significantly, while plasma clearance decreased significantly in clopidogrel normal-dose and high-dose groups; the duration of LORR in rats was prolonged by 19.5% and 23.9%, with statistical difference (P<0.05). However, there was no statistically significant difference in the pharmacokinetic parameters or LORR duration of ciprofol between the different dose groups of clopidogrel (P>0.05). CONCLUSIONS Clopidogrel could inhibit the metabolism of ciprofol in rats and prolong the duration of LORR.
4.Guangxi expert consensus on rapid comprehensive evaluation of oral dihydropyridine calcium channel blockers in the treatment of cardiovascular disease
Siru ZHOU ; Yue QIU ; Weipei SHEN ; Zhenguang HUANG ; Xiaoyu CHEN ; Hongliang ZHANG
China Pharmacy 2025;36(7):769-778
OBJECTIVE To conduct a rapid and comprehensive evaluation of commonly used oral dihydropyridine calcium channel blockers (DHP CCBs) in Guangxi, and provide scientific basis for clinical medication and drug selection in medical institutions. METHODS Based on the actual drug use data of public medical institutions at the second level and above in Guangxi Zhuang Autonomous Region, and based on the national centralized collection catalog, commonly used oral DHP CCBs were selected. The Professional Committee of Evidence-based Pharmacy of the Guangxi Pharmaceutical Association organized relevant experts from multiple medical institutions in the region to conduct a quantitative scoring of the selected oral DHP CCBs from five key dimensions of pharmaceutical characteristics, effectiveness, safety, economy, and other attributes, by referring to the Quick Guideline for Drug Evaluation and Selection in Chinese Medical Institutions (the Second Edition), combined with the latest evidence-based medical research results, and widely soliciting suggestions from clinical and pharmaceutical experts. Finally, the Guangxi Expert Consensus on Rapid Comprehensive Evaluation of Oral Dihydropyridine Calcium Channel Blockers in the Treatment of Cardiovascular Disease was formulated. RESULTS A total of 30 commonly used oral DHP CCBs were selected. Among them, Amlodipine besylate tablets (Huizhi) demonstrated superior comprehensive performance (81.79 points), excelling particularly in pharmaceutical properties, effectiveness and other attributes. The compound scores of Amlodipine besylate tablets (Chongqing Yaoyou) and Amlodipine besylate tablets (Suzhou Dongrui) ranked second and third respectively, with scores of 81.66 and 81.60 points. CONCLUSIONS This consensus can provide guidance and decision-making support for the rational clinical application of oral DHP CCBs in Guangxi Region and the selection of drug directories in medical institutions.
5.Concentration and source analysis of polycyclic aromatic hydrocarbons in PM2.5 during heating period in Yantai City
Tiantian ZHANG ; Ying WANG ; Zhiyu WANG ; Tianran ZHANG ; Wenna GUO ; Songsong WANG ; Xiaoyu ZHANG
Journal of Environmental and Occupational Medicine 2025;42(4):415-419
Background Polycyclic aromatic hydrocarbons (PAHs) are widely known atmospheric pollutants, which can cause serious harm to human body and ecological environment. Objective To analyze the concentrations and sources of PAHs in atmospheric PM2.5 in Zhifu District and Longkou City during the heating period in Yantai. Methods Two monitoring sites in Zhifu District and Longkou City of Yantai were selected, and PM2.5 sample collection was carried out from April 2023 to March 2024. Gas chromatography-mass spectrometry was applied to analyze the concentrations of PAHs in atmospheric PM2.5 during the heating period (from November 2023 to March 2024) and the non-heating period (from April to October 2023). The concentrations of PAHs in the two periods were compared and the sources of PAHs during the heating period were analyzed by characteristic ratio method. Results During the heating period, the total concentration ranges of PAHs in atmospheric PM2.5 at the monitoring sites in Zhifu District and Longkou City of Yantai were (1.59-23.70) ng·m−3 and (2.08-149.72) ng·m−3 respectively, and the medians (M) and the 25th and 75th percentiles (P25, P75) were 4.99 (2.61, 8.09) ng·m−3 and 15.46 (8.15, 29.05) ng·m−3 respectively. The PAHs concentrations in Longkou City were significantly higher than those in Zhifu District in all months (P<0.05). The highest median total concentrations of PAHs in both sites were reported in January (8.14 ng·m−3 and 81.56 ng·m−3 respectively). In the non-heating period, the M (P25, P75) of the total PAHs concentrations at the two sites were 1.59 (1.59, 2.78) ng·m−3 and 4.11 (2.94, 7.97) ng·m−3 respectively, much lower than those in the heating period (P<0.01). The order of composition of PAHs by ring number in PM2.5 at both sites was 4-ring> 5-ring> 6-ring, with the 4-ring contributing the largest proportion (65.33% and 46.39% respectively). Fluoranthene had the highest concentration among PAHs at both sites, with concentrations M (P25, P75) of 1.29 (0.51, 1.78) ng·m−3 and 2.32 (1.30, 3.82) ng·m−3 respectively. The characteristic ratios of fluoranthene/(fluoranthene + pyrene), fluoranthene/pyrene, benzo[a]anthracene/(benzo[a]anthracene + chrysene), pyrene/benzo[a]pyrene, benzo[a]pyrene/(benzo[a]pyrene + chrysene), benzo[a]pyrene/benzo[g,h,i]pyrene, and indeno[1,2,3-c,d]pyrene/(indeno[1,2,3-c,d]pyrene + benzo[g,h,i]pyrene) in Zhifu District were 0.62, 1.65, 0.41, 4.48, 0.50, 0.93 and 0.47 respectively, and those in Longkou were 0.57, 1.35, 0.40, 2.89, 0.29, 0.79 and 0.47 respectively. The results showed that PAHs pollutants were generated by combination of coal combustion, vehicle exhaust emissions and gasoline combustion. Conclusion During the heating period in Yantai area, the total concentration of PAHs in atmospheric PM2.5 is significantly higher than that in the non-heating period. Among them, during the heating period, the pollution level in Longkou City is significantly higher than that in Zhifu District. The local PAHs may be sourced from mixed pollution, and the main sources include gasoline, and coal combustion and vehicle exhaust emissions.
6.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.
7.Study on meal preferences of school aged children based on discrete choice experiment
Chinese Journal of School Health 2025;46(1):45-49
Objective:
To explore the relative importance of different food attributes and levels in food decision making of school aged children, and to understand their meal preferences, so as to provide the evidence for formulating precise intervention strategies for dietary behaviours of school aged children.
Methods:
From May to June 2024, a total of 854 children aged 11 to 15 years old were selected from 2 middle schools (each school in urban and rural areas) in both Hubei Province and Anhui Province by stratified cluster random sampling method to conduct a D-optimal discrete choice experiment. The mixed Logit model was used to analyze children s preference for meal attributes and different levels, and to calculate the relative importance (RI) of attributes and willingness to pay (WTP) in meal choices.
Results:
The included five food attributes had statistical significance on meal choice of school aged children ( P <0.05). The relative importance of food attributes affecting the meal choices of school aged children in descending order were dining mode ( RI =31.26%), food varieties ( RI =30.56%), cooking method( RI =23.84%), taste( RI =8.06%) and price ( RI =6.27%). Among them, school aged children preferred home cooked meals ( β =0.74) (WTP=86.3 yuan),varied foods(grain/tubers+vegetables+fish, meat, eggs and beans) ( β =0.61) (WTP=71.9 yuan), fried/roasted cooking ( β =0.51) and spicy taste ( β =0.33).Price was negatively correlated with meal choices( β =-0.01) ( P <0.05). Based on residential area and body mass index (BMI), the stratified analysis showed that dining mode was highest in the relative importance for rural children with overweight and obese children ( RI =31.28%,34.17%), both of whom preferred home cooked meals ( β =0.76, 0.91), and meals containing fish, meat, eggs and beans with grain/tubers or grain/tubers and vegetables in terms of food choice (area: β =0.53, 0.53 ; BMI: β =0.55, 0.56) ( P <0.05).
Conclusions
School aged children have different preferences for different attributes of meals. The quality of school meals should be improved,the cost of buying healthy meals should be reduced,targeted family health education should be carried out,and healthy cooking methods should be advocated.
8.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.
9.Dynamics of eosinophil infiltration and microglia activation in brain tissues of mice infected with Angiostrongylus cantonensis
Fanna WEI ; Renjie ZHANG ; Yahong HU ; Xiaoyu QIN ; Yunhai GUO ; Xiaojin MO ; Yan LU ; Jiahui SUN ; Yan ZHOU ; Jiatian GUO ; Peng SONG ; Yanhong CHU ; Bin XU ; Ting ZHANG ; Yuchun CAI ; Muxin CHEN
Chinese Journal of Schistosomiasis Control 2025;37(2):163-175
Objective To investigate the changes in eosinophil counts and the activation of microglial cells in the brain tissues of mice at different stages of Angiostrongylus cantonensis infection, and to examine the role of microglia in regulating the progression of angiostrongyliasis and unravel the possible molecular mechanisms. Methods Fifty BALB/c mice were randomly divided into the control group and the 7-d, 14-d, 21-day and 25-d infection groups, of 10 mice in each group. All mice in infection groups were infected with 30 stage III A. cantonensis larvae by gavage, and animals in the control group was given an equal amount of physiological saline. Five mice were collected from each of infection groups on days 7, 14, 21 d and 25 d post-infection, and 5 mice were collected from the control group on the day of oral gavage. The general and focal functional impairment was scored using the Clark scoring method to assess the degree of mouse neurological impairment. Five mice from each of infection groups were sacrificed on days 7, 14, 21 d and 25 d post-infection, and 5 mice from the control group were sacrificed on the day of oral gavage. Mouse brain tissues were sampled, and the pathological changes of brain tissues were dynamically observed using hematoxylin and eosin (HE) staining. Immunofluorescence staining with eosinophilic cationic protein (ECP) and ionized calcium binding adaptor molecule 1 (Iba1) was used to assess the degree of eosinophil infiltration and the counts of microglial cells in mouse brain tissues in each group, and the morphological parameters of microglial cells (skeleton analysis and fractal analysis) were quantified by using Image J software to determine the morphological changes of microglial cells. In addition, the expression of M1 microglia markers Fcγ receptor III (Fcgr3), Fcγ receptor IIb (Fcgr2b) and CD86 antigen (Cd86), M2 microglia markers Arginase 1 (Arg1), macrophage mannose receptor C-type 1 (Mrc1), chitinase-like 3 (Chil3), and phagocytosis genes myeloid cell triggering receptor expressed on myeloid cells 2 (Trem2), CD68 antigen (Cd68), and apolipoprotein E (Apoe) was quantified using real-time quantitative reverse transcription PCR (RT-qPCR) assay in the mouse cerebral cortex of mice post-infection. Results A large number of A. cantonensis larvae were seen on the mouse meninges surface post-infection, and many neuronal nuclei were crumpled and deeply stained, with a large number of bleeding points in the meninges. The median Clark scores of mouse general functional impairment were 0 (interquartile range, 0), 0 (interquartile range, 0.5), 6 (interquartile range, 1.0), 14 (interquartile range, 8.5) points and 20 (interquartile range, 9.0) points in the control group and the 7-d, 14-d, 21-d and 25-d groups, respectively (H = 22.45, P < 0.01), and the median Clark scores of mouse focal functional impairment were 0 (interquartile range, 0), 2 (interquartile range, 2.5), 7 (interquartile range, 3.0), 18 (interquartile range, 5.0) points and 25 (interquartile range, 6.5) points in the control group and the 7-d, 14-d, 21-d and 25-d groups, respectively (H = 22.72, P < 0.01). The mean scores of mice general and focal functional impairment were all higher in the infection groups than in the control group (all P values < 0.05). Immunofluorescence staining showed a significant difference in the eosinophil counts in mouse brain tissues among the five groups (F = 40.05, P < 0.000 1), and the eosinophil counts were significantly higher in mouse brain tissues in the 14-d (3.08 ± 0.78) and 21-d infection groups (5.97 ± 1.37) than in the control group (1.00 ± 0.28) (both P values < 0.05). Semi-quantitative analysis of microglia immunofluorescence showed a significant difference in the counts of microglial cells among the five groups (F = 17.66, P < 0.000 1), and higher Iba1 levels were detected in mouse brain tissues in 14-d (5.75 ± 1.28), 21-d (6.23 ± 1.89) and 25-d infection groups (3.70 ± 1.30) than in the control group (1.00 ± 0.30) (all P values < 0.05). Skeleton and fractal analyses showed that the branch length [(162.04 ± 34.10) μm vs. (395.37 ± 64.11) μm; t = 5.566, P < 0.05] and fractal dimension of microglial cells (1.30 ± 0.01 vs. 1.41 ± 0.03; t = 5.266, P < 0.05) were reduced in mouse brain tissues in the 21-d infection group relative to the control group. In addition, there were significant differences among the 5 groups in terms of M1 and M2 microglia markers Fcgr3 (F = 48.34, P < 0.05), Fcgr2b (F = 55.46, P < 0.05), Cd86 (F = 24.44, P < 0.05), Arg1 (F = 31.18, P < 0.05), Mrc1 (F = 15.42, P < 0.05) and Chil3 (F = 24.41, P < 0.05), as well as phagocytosis markers Trem2 (F = 21.19, P < 0.05), Cd68 (F = 43.95, P < 0.05) and Apoe (F = 7.12, P < 0.05) in mice brain tissues. Conclusions A. cantonensis infections may induce severe pathological injuries in mouse brain tissues that are characterized by massive eosinophil infiltration and persistent activation of microglia cells, thereby resulting in progressive deterioration of neurological functions.
10.Targeting effect and anti-tumor mechanism of folic acid-modified crebanine nanoparticles combined with ultra-sound irradiation on M109 cells in vitro and in vivo
Hailiang ZHANG ; Xiaoyu ZHAO ; Jiahua MEI ; Rui PAN ; Junze TANG ; Kun YU ; Rui XUE ; Xiaofei LI ; Xin CHENG
China Pharmacy 2025;36(14):1730-1736
OBJECTIVE To investigate the targeting effect of folic acid-modified crebanine nanoparticles (FA-Cre@PEG- PLGA NPs, hereinafter referred to as “NPs”) combined with ultrasound irradiation on M109 cells in vitro and in vivo after administration, and explore the anti-tumor mechanism. METHODS CCK-8 assay was used to detect the inhibitory effect of NPs combined with ultrasound irradiation on the proliferation of M109 cells, and the best ultrasound time was selected. Using human lung cancer A549 cells as a control, the targeting of NPs combined with ultrasound irradiation to M109 cells was evaluated by free folic acid blocking assay and cell uptake assay. The effects of NPs combined with ultrasound irradiation on the migration, invasion, apoptosis, cell cycle and reactive oxygen species (ROS) levels of M109 cells were detected by cell scratch test, Transwell chamber test and flow cytometry at 1 h after 958401536@qq.com administration; the changes of mitochondrial membrane potential (MMP) were observed by fluorescence inverted microscope. A mouse subcutaneous tumor model of M109 cells was constructed, and the in vivo tumor targeting of NPs combined with ultrasound irradiation was investigated by small animal in vivo imaging technology. RESULTS NPs combined with ultrasound irradiation could significantly inhibit the proliferation of M109 cells, and the optimal ultrasound time was 1 h after administration. The free folic acid could antagonize the inhibitory effect of NPs on the proliferation of M109 cells, and combined with ultrasound irradiation could partially reverse this antagonism. Compared with A549 cells, the uptake rate of NPs in M109 cells was significantly higher (P<0.01), and ultrasound irradiation could promote cellular uptake. NPs combined with ultrasound irradiation could inhibit the migration and invasion of M109 cells and block the cell cycle in the G0/G1 and G2/M phases. Compared with control group, the apoptosis rate of M109 cells and ROS level were increased significantly (P<0.01), while the MMP decreased significantly (P<0.01) in the different concentration (100, 200, 300 μg/mL) groups of M109 cells. Compared with the mice in non-ultrasound group, the fluorescence intensity and tumor-targeting index of the tumor site in the 0 h ultrasound group were significantly enhanced (P<0.05 or P<0.01). CONCLUSIONS NPs combined with ultrasound irradiation have a strong targeting effect on M109 cells in vitro and in vivo, the anti-tumor mechanism includes inhibiting cell migration and invasion, blocking cell cycle, and inducing apoptosis.


Result Analysis
Print
Save
E-mail