1.An integrated optoelectronic fiber for simultaneous transmission of laser and electrical current and validation of tissue vaporization in ex vivo pig kidneys
Dongchong SUN ; Yutao ZHANG ; Likun GAI ; Chenglin ZHANG ; Yanna WANG ; Hao ZHANG ; Yalin SUN ; Yongmei WANG
Journal of Modern Urology 2026;31(2):168-171
Objective To design and fabricate an integrated optoelectrical fiber to enable the simultaneous transmission of high-power laser and electrical current, thereby developing a novel tool for urological surgery.Methods A miniature metal sleeve was installed at the front end of a medical high-energy optical fiber, and corresponding conductive circuits were configured. The fiber was connected to a fiber thulium laser and a bipolar plasma generator simultaneously. Experiments of simulated vaporization were conducted on ex vivo porcine kidney tissues using thulium laser (50 W), plasma (100 W), and thulium laser + plasma (50 W+100 W), respectively. Tissue removal efficiency was calculated using the weighing method:tissue clearance rate (g/min)=[mass before vaporization (g) - mass after vaporization (g)]/vaporization time (min). Lateral tissue thermal damage was assessed with hematoxylin-eosin (HE) staining. One-way analysis of variance and least significant difference test were used for statistical analysis.Results The integrated optoelectrical fiber was successfully constructed, which could simultaneously and continuously transmit thulium laser and plasma electrocision current. The tissue clearance rate of the thulium laser+plasma group was significantly higher than that of the thulium laser group and plasma group [(0.49±0.13) g/min vs. (0.14±0.02) g/min vs. (0.11±0.04) g/min, P<0.001]. The average lateral thermal damage depth of the thulium laser + plasma group showed no statistically significant difference compared to the thulium laser group [(985.5±178.5) μm vs.(957.5±197.4) μm, P>0.05], but both were significantly higher than that of the simple plasma group [(499.6±78.0) μm] (P<0.001). Conclusion The thulium laser + plasma energy transmitted simultaneously by the integrated optoelectrical fiber can vaporize kidney tissue more efficiently without additional thermal damage.
2.Mechanism of Sorbus tianschanica in regulating asthmatic airway inflammation through TLR4/PI3K/Akt/MMP9 signaling pathway.
Wen-Kai WANG ; Jun-Min CHANG ; Xiao-Li MA ; Gai-Ru LI
China Journal of Chinese Materia Medica 2025;50(15):4304-4314
To investigate the effects and mechanisms of the water extract from Sorbus tianschanica(STE) on asthmatic airway inflammation, the mice were randomly divided into six groups, including a control group, a model group, a positive drug dexamethasone group(2 mg·kg~(-1)), a low-dose STE group(1 g·kg~(-1)), a medium-dose STE group(2 g·kg~(-1)), and a high-dose STE group(4 g·kg~(-1)). Except for the control group, all groups were subjected to ovalbumin induction to establish an asthma mouse model. The anti-inflammatory effects of STE were evaluated by examining pathological changes in lung tissue and measuring the levels of interleukin(IL)-4 and IL-5 in bronchoalveolar lavage fluid(BALF). Transcriptomic and proteomic methods were further employed to analyze differentially expressed genes and proteins, as well as their associated signaling pathways in lung tissue. Subsequently, the expression changes of key genes were verified by reverse transcription-quantitative polymerase chain reaction(RT-qPCR), and immunohistochemistry and Western blot methods were used to explore the regulatory mechanisms of STE in the pathogenesis of asthma in mice. Molecular docking was performed by using AutoDock Vina software to evaluate the binding affinity of the main active components in STE with the target proteins, including phosphatidylinositol-3-kinase catalytic subunit α(PIK3CA), Toll-like receptor 4(TLR4), protein kinase B1(Akt1), and matrix metallopeptidase 9(MMP9). The results showed significant inflammatory cell infiltration and fibrous tissue proliferation in the lung tissue of mice in the model group. However, these pathological changes were markedly reduced following STE intervention. Compared with those of the control group, the expression levels of IL-4 and IL-5 in the BALF of the model group were significantly increased but notably decreased following STE intervention. Transcriptomic and proteomic analyses identified key genes and proteins associated with allergic asthma, including tumor necrosis factor(TNF), IL-6, TLR4, PIK3CA, and MMP9. RT-qPCR validation revealed that high-dose STE intervention significantly downregulated the expressions of PIK3CA, IL-6, Akt1, MMP9, IL-13, nuclear factor-kappa B(NF-κB), TNF, CXC motif chemokine ligand 1(CXCL1), and TLR4 mRNAs and significantly upregulated the expression of signal transducer and activator of transcription 1(STAT1) mRNA. Western blot and immunohistochemical analyses confirmed that STE significantly downregulated the expressions of MMP9, TLR4, PIK3CA, and phosphorylated protein kinase B(p-Akt) in lung tissue of asthmatic mice. Moreover, molecular docking demonstrated that kaempferol-3,7-diglucoside, isoquercitrin, quercetin-3-gentiobioside, and hyperoside in STE exhibited stable binding affinities with PIK3CA, TLR4, Akt1, and MMP9, suggesting that the active components may exert anti-inflammatory effects by targeting and modulating asthma-related signaling pathways. In summary, STE exerts anti-asthmatic effects by inhibiting the expressions of PIK3CA, MMP9, p-Akt, and TLR4 and regulating the TLR4/PI3K/Akt/MMP9 signaling pathway.
Animals
;
Asthma/metabolism*
;
Toll-Like Receptor 4/metabolism*
;
Signal Transduction/drug effects*
;
Mice
;
Phosphatidylinositol 3-Kinases/metabolism*
;
Proto-Oncogene Proteins c-akt/metabolism*
;
Matrix Metalloproteinase 9/metabolism*
;
Mice, Inbred BALB C
;
Drugs, Chinese Herbal/administration & dosage*
;
Female
;
Humans
;
Lung/immunology*
;
Male
3.Traditional Chinese Exercise Improves Lung Function and Exercise Capacity in Patients with Preserved Ratio Impaired Spirometry.
Yan-Yi LIU ; Gai-Hua HOU ; Kun XIA ; Xiao-Yan YAO ; Yi WANG ; Guang-Xi LI
Chinese journal of integrative medicine 2025;31(12):1113-1118
OBJECTIVE:
To investigate the effect of traditional Chinese Five-body balance exercise on patients with preserved ratio impaired spirometry (PRISm).
METHODS:
Fifteen patients with PRISm and 15 patients diagnosed with chronic obstructive pulmonary disease (COPD) were recruited from the Outpatient Department of Guang'anmen Hospital and Beijing Niujie Health Service Center from April to December, 2023. Participants in both groups attended supervised Five-body balance exercise training twice a week for 12 weeks. Patients with COPD continued their regular medication regimen during the intervention period. The endpoints were mean changes in the 6-min walk test (6MWT), St. George's Respiratory Questionnaire (SGRQ) score, cardiopulmonary exercise testing (CPET), pulmonary function, and scores of COPD assessment test (CAT), modified British Medical Research Council, Self-Rating Anxiety Scale, and Self-Rating Depression Scale from baseline to 12 weeks. Adverse events were monitored throughout the study.
RESULTS:
The PRISm group showed a significant improvement from baseline to week 12 in 6MWT, SGRQ symptom score, and forced vital capacity (FVC) compared to the COPD group (P<0.05). No significant between-group changes were observed in other outcome measurements (P>0.05). In addition, compared with baseline, both groups exhibited improvements in 6MWT, SGRQ score, and CPET at week 12 (P<0.05). The PRISm group also showed a significant increase in forced expiratory volume in 1 s and FVC, as well as a significant decrease in CAT score at week 12 (P<0.05). No adverse events were reported.
CONCLUSION
Patients with PRISm may benefit from Five-body balance exercise training, which can improve the exercise capacity, health-related quality of life, and lung function. (Registration No. ChiCTR2200059290).
Humans
;
Spirometry
;
Male
;
Female
;
Pulmonary Disease, Chronic Obstructive/therapy*
;
Lung/physiopathology*
;
Middle Aged
;
Exercise Tolerance/physiology*
;
Exercise Therapy
;
Aged
;
Medicine, Chinese Traditional
;
Respiratory Function Tests
;
East Asian People
4.Pseudolaric Acid B Alleviates Non-alcoholic Fatty Liver Disease by Targeting PPARα to Regulate Lipid Metabolism and Promote Mitochondrial Biogenesis.
Shu-Yan LIU ; Xiao-Wei ZHANG ; Gai GAO ; Chang-Xin LIU ; Hui CHEN ; Zhong-Xue FU ; Jiang-Yan XU ; Zhen-Zhen WANG ; Zhen-Qiang ZHANG ; Zhi-Shen XIE
Chinese journal of integrative medicine 2025;31(10):877-888
OBJECTIVE:
To investigate the therapeutic potential of pseudolaric acid B (PAB) on non-alcoholic fatty liver disease (NAFLD) and its underlying molecular mechanism in vitro and in vivo.
METHODS:
Eight-week-old male C57BL/6J mice (n=32) were fed either a normal chow diet (NCD) or a high-fat diet (HFD) for 8 weeks. The HFD mice were divided into 3 groups according to a simple random method, including HFD, PAB low-dose [10 mg/(kg·d), PAB-L], and PAB high-dose [20 mg/(kg·d), PAB-H] groups. After 8 weeks of treatment, glucose metabolism and insulin resistance were assessed by oral glucose tolerance test (OGTT) and insulin tolerance test (ITT). Biochemical assays were used to measure the serum and cellular levels of total cholesterol (TC), triglycerides (TG), aspartate aminotransferase (AST), alanine aminotransferase (ALT), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C). White adipose tissue (WAT), brown adipose tissue (BAT) and liver tissue were subjected to hematoxylin and eosin (H&E) staining or Oil Red O staining to observe the alterations in adipose tissue and liver injury. PharmMapper and DisGeNet were used to predict the NAFLD-related PAB targets. Peroxisome proliferator-activated receptor alpha (PPARα) pathway involvement was suggested by Kyoto Encyclopedia of Genes and Genomes (KEGG) and search tool Retrieval of Interacting Genes (STRING) analyses. Luciferase reporter assay, cellular thermal shift assay (CETSA), and drug affinity responsive target stability assay (DARTS) were conducted to confirm direct binding of PAB with PPARα. Molecular dynamics simulations were applied to further validate target engagement. RT-qPCR and Western blot were performed to assess the downstream genes and proteins expression, and validated by PPARα inhibitor MK886.
RESULTS:
PAB significantly reduced serum TC, TG, LDL-C, AST, and ALT levels, and increased HDL-C level in HFD mice (P<0.01). Target prediction analysis indicated a significant correlation between PAB and PPARα pathway. PAB direct target binding with PPARα was confirmed through luciferase reporter assay, CETSA, and DARTS (P<0.05 or P<0.01). The target engagement between PAB and PPARα protein was further confirmed by molecular dynamics simulations and the top 3 amino acid residues, LEU321, MET355, and PHE273 showed the most significant changes in mutational energy. Subsequently, PAB upregulated the genes expressions involved in lipid metabolism and mitochondrial biogenesis downstream of PPARα (P<0.05 or P<0.01). Significantly, the PPARα inhibitor MK886 effectively reversed the lipid-lowering and PPARα activation properties of PAB (P<0.05 or P<0.01).
CONCLUSION
PAB mitigates lipid accumulation, ameliorates liver damage, and improves mitochondrial biogenesis by binding with PPARα, thus presenting a potential candidate for pharmaceutical development in the treatment of NAFLD.
Animals
;
PPAR alpha/metabolism*
;
Non-alcoholic Fatty Liver Disease/pathology*
;
Male
;
Mice, Inbred C57BL
;
Lipid Metabolism/drug effects*
;
Diterpenes/therapeutic use*
;
Organelle Biogenesis
;
Diet, High-Fat
;
Humans
;
Mice
;
Liver/metabolism*
;
Insulin Resistance
;
Mitochondria/metabolism*
;
Molecular Docking Simulation
5.Correlation between carotid-femoral pulse wave velocity and hemodynamic parameters of ultrasound for carotid artery and heart
Xia MA ; Ying HUI ; Jianjiao WANG ; Siyu WANG ; Mo ZHANG ; Wei HUANG ; Xinyu ZHAO ; Gai LI ; Xianquan SHI
China Medical Equipment 2025;22(5):16-21
Objective:To investigate the correlation between carotid-femoral pulse wave velocity(cfPWV)and carotid artery structural,hemodynamic,and cardiac functional parameters.Methods:A total of 420 healthy volunteers who underwent neck ultrasound,cardiac ultrasound,and cfPWV examination at Kailuan General Hospital from June 2022 to February 2023 were selected,and they were divided into two groups based on the atherosclerosis threshold value of cfPWV>10 m/s,which included high cfPWV group(140 cases,cfPWV>10 m/s)and low cfPWV group(280 cases,cfPWV≤10 m/s).The demographic data(age,sex)of 420 persons were collected,and the common carotid artery diameter(CCAD),common carotid artery intima-media thickness(CIMT),plaque status,peak systolic velocity(PSV),end-diastolic velocity(EDV)and mean flow velocity(MFV)were compared between two groups.Then,the differences of interventricular septal thickness(IVST)of heart,left ventricular posterior wall thickness(LVPWT),the ratio of blood flow velocity at early stage to that at advanced stage in mitral valve(E/A)and stroke volume(SV)were analyzed.Multivariate logistic regression was adopted to analyze the independent influence factors of cfPWV enhancement.Results:The average age of high cfPWV group was(61.31±9.66)years old,which was significantly higher than(51.06±10.47)years old of low cfPWV group,and the difference of that was significant(t=-9.56,P<0.01).In the parameters of common carotid artery,63 persons(45.0%)occurred plaque in 140 persons of high cfPWV group,which was significantly lower than 50 persons(17.86%)in 280 persons of low cfPWV group,and the difference of that between two groups was significant(x2=34.97,P<0.05).The differences of CCAD,CIMT,PSV,EDV and MV of common carotid artery at right side of persons between two groups were significant(t=-2.16,-5.40,4.52,5.59,5.04,P<0.05),respectively.The parameters of heart showed that the LVPWT thickness increased(9.35±1.13)mm,and the ratio of E/A<1 increased 77.86%in high cfPWV group,which were significantly related to the increase of cfPWV(r=0.27,0.38,P<0.01).Multivariate logistic regression analysis indicated that age(OR=1.05,95%CI:1.02-1.08),CCAD(OR=1.63,95%CI:1.22-2.16),plaque presence(OR=1.84,95%CI:1.07-3.17),LVPWT(OR=1.35,95%CI:1.05-1.72),and the ratio of E/A<1(OR=2.37,95%CI:1.32-4.26)were independent predictors of cfPWV enhancement.Conclusion:The enhancement of cfPWV is closely related to high age,the reconstruction of common carotid artery(widening of inside diameter,and plaque formation),left ventricular hypertrophy,and diastolic abnormality,which indicates it is possible that atherosclerosis process accompanies by the change of interaction mechanism of blood vessels-heart.
6.Research of routine ultrasound examination combined with CTV angiography for lower extremity veins in assessing deep venous thrombosis of lower extremity after ischemic stroke
Tianying LIU ; Xin DUAN ; Gai ZHANG ; Wenli WANG
China Medical Equipment 2025;22(3):63-67
Objective:To analyze the effect of routine ultrasound examination combined with computed tomography venous(CTV)angiography for lower extremity veins in assessing deep vein thrombosis(DVT)of lower extremity after ischemic stroke.Methods:The clinical data of 132 patients with ischemic stroke,who admitted to XiDian Group Hospital from January 2020 to May 2023,were retrospectively analyzed.All selected patients were suspected as DVT in lower extremity,so they underwent digital subtraction angiography(DSA),routine ultrasound and CTV examination for lower extremity veins.The result of DSA examination was used as the gold standard.The diagnostic efficacy of routine ultrasound examination combined with CTV for the DVT of lower extremity after stroke was further analyzed.Results:The results of DSA examination confirmed that a total of 128 cases of 132 patients with suspected DVT were diagnosed as DVT in lower extremity.The routine ultrasound on lower extremity found out about 102 cases with DVT on lower extremity,and the consistency between the results of ultrasound diagnosis and the results of DSA diagnosis was general(Kappa=0.461,P=0.000).The CTV found out about 111 cases with DVT on lower extremity,and the consistency between the results of CTV diagnosis and the results of DSA diagnosis also was general(Kappa=0.605,P=0.000).The diagnostic result of the combination of routine ultrasound and CTV for DVT in lower extremity had better consistency with DSA result(Kappa=0.752,P=0.000).The diagnostic accuracy(93.33%),sensitivity(94.53%)and negative predictive value(73.08%)of ultrasound combined with CTV were significantly higher than those of single diagnosis,and the differences of them were statistically significant(x2=10.727,12.463,6.313,P<0.05).Conclusion:The diagnosis of the routine ultrasound examination combined with CTV for DVT of lower extremity after ischemic stroke can improve the accuracy and diagnostic efficacy of clinical diagnosis,which is contribute to the assessment of patients'disease conditions.
7.Association between household solid fuel use for cooking and depressive symptoms among middle-aged and elderly adults in rural China: Evidence from the China Family Panel Studies Database
Ting YANG ; Yong LIU ; Xufeng LI ; Yun GAI ; Zhihao XIE ; Junkui WANG ; Yong YU ; Jingxuan WANG
Journal of Environmental and Occupational Medicine 2025;42(8):926-931
Background Although current evidence suggests a link between outdoor air pollution and depressive symptoms, the effect of solid fuel use (a significant indoor air pollutant) on depressive symptoms in China's rural middle-aged and elderly population remains poorly understood. Objective To explore the association between solid fuel use for cooking and depressive symptoms among middle-aged and elderly people in rural areas of China, and to provide a basis for the prevention and control of depressive symptoms among residents in rural areas. Methods Data were obtained from the 2020 China Family Panel Studies (CFPS), depressive symptoms were assessed using 8-item Center for Epidemiologic Studies Depression Scale (CES-D), and cooking fuel type was self-reported. Subsequently, two-level binary unconditional logistic regression models were fitted to assess the impact of solid fuel use for cooking on depressive symptoms. Results A total of
8.Metabolomics Reveals Immune System Domage of Dictamnine
Xiaocan GAI ; Jiaxin RUAN ; Sujie LIU ; Chen WANG ; Xiaofan WANG ; Jiahe YAN ; Yu WANG ; Fang LU ; Shumin LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(20):57-65
ObjectiveTo explore the mechanism of the immunotoxicity induced by dictamnine (DIC) in rats and the recovery effect after drug withdrawal by ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry, thereby providing a theoretical basis for elucidating the toxic mechanism of DIC. MethodsSD rats were randomized into blank (normal saline), DIC (10 mg·kg-1), and DIC withdrawal (recovery period) groups (n=8). The rats were continuously treated for 7 days, once a day, and the body weight and organ weight were recorded. The levels of interleukin-1 (IL-1), IL-6, and tumor necrosis factor-α (TNF-α) in the serum and immunoglobulin A (IgA), immunoglobulin G (IgG), and immunoglobulin M (IgM) in the spleen were determined by enzyme-linked immunosorbent assay. Hematoxylin-eosin staining was used to observe the pathological changes in the spleen. ultra performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) was employed to screen the potential biomarkers of immune inflammation caused by DIC, and pathway enrichment analysis and correlation analysis were performed. The mRNA levels of IL-1β, TNF-α, lysophosphatidylcholine acyltransferase 2 (LPCAT2), and farnesoid X receptor (FXR) in the serum were determined by Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR). ResultsCompared with the blank group, the DIC group showed elevated levels of IL-1β, IL-6, and TNF-α in the serum (P<0.01), and the DIC withdrawal group showcased lowered levels of IL-1β, IL-6, and TNF-α in the serum (P<0.01). The levels of IgA, IgG, and IgM in the spleen of rats in the DIC group were decreased (P<0.01), while those in the DIC withdrawal group were recovered (P<0.05, P<0.01). Untargeted metabolomics of the serum and spleen screened out 14 common differential metabolites and 14 common metabolic pathways. The Spearman correlation analysis between differential metabolites and inflammatory factors identified PC (32∶0), LysoPC (20∶4/0∶0), LysoPC (P-18∶0/0∶0), taurochenodeoxycholic acid, taurocholic acid, LysoPC [20∶5(5Z,8Z,11Z,14Z,17Z)/0∶0], chenodeoxycholic acid, arachidonic acid, LysoPC (18∶0/0∶0), LysoPC (15∶0/0∶0), LysoPC (16∶0/0∶0), and LysoPC (17∶0/0∶0) as the biomarkers of immunotoxicity induced by DIC in SD rats. In the process of immunotoxicity caused by DIC, lipid metabolism disorders such as glycerophospholipid metabolism, primary bile acid metabolism, and arachidonic acid metabolism were enriched, which was consistent with the DIC-induced inflammatory factors and pathological characteristics of the spleen. Compared with the blank group, the DIC group exhibited up-regulated mRNA levels of IL-1β, TNF-α, LPCAT2, and FXR (P<0.01), and the up-regulation was decreased in the withdrawal group (P<0.01). ConclusionDIC can lead to immune and inflammatory disorders. DIC withdrawal can regulate the expression of biomarkers related to serum and spleen metabolites, regulate the inflammatory metabolic pathway, reduce the inflammation level, and alleviate the metabolic disorders, thus attenuating the potential toxicity induced by DIC.
9.Expression and Clinical Significance of Class Ⅰ Histone Deacetylases in the Serum of Patients With Psoriatic Arthritis.
Ming-Hui ZHANG ; Wen-Xiu DONG ; Jia WANG ; Gai-Lian ZHANG
Acta Academiae Medicinae Sinicae 2025;47(4):557-566
Objective To investigate the expression levels of class Ⅰ histone deacetylases(HDAC)in the serum of patients with newly diagnosed psoriatic arthritis(PsA)and screen out serological indicators that are of significance for early diagnosis and assessment of disease activity.Methods A total of 49 PsA patients newly diagnosed in Shanxi Provincial People's Hospital from August 2022 to February 2024 and 30 healthy individuals(control group)were enrolled in this study.Demographic data were collected,and disease severity was assessed.Serum samples were collected,and the expression levels of class Ⅰ HDAC(HDAC1,HDAC2,HDAC3,and HDAC8)in the serum of each group were determined by ELISA.The correlations between the expression levels of class Ⅰ HDAC and clinical assessment indicators in each group were evaluated.Multivariate Logistic regression was adopted to analyze the risk factors affecting the disease activity of PsA patients.The receiver operating characteristic curve was used to evaluate the diagnostic efficacy of the risk factors affecting the disease activity of PsA patients.Results Compared with the control group,PsA patients showed up-regulated expression levels of HDAC1(P=0.003),HDAC2(P=0.010),HDAC3(P=0.003),and HDAC8(P=0.018)in the serum.The serum HDAC1 level of PsA patients was positively correlated with erythrocyte sedimentation rate(r=0.344,P=0.028).The serum HDAC2 level was positively correlated with the overall assessment of disease activity(r=0.468,P=0.001),the disease activity index of arthritis(r=0.401,P=0.007),the number of swollen joints(r=0.308,P=0.042),hospital anxiety and depression scale(HADS)score of anxiety(r=0.360,P=0.018),and HADS score of depression(r=0.302,P=0.047).The serum HDAC3 level was correlated with erythrocyte sedimentation rate(r=0.542,P<0.001),C-reactive protein(CRP)level(r=0.440,P<0.001),HADS score of anxiety(r=0.420,P=0.005),interleukin-6 level(r=0.397,P=0.004),the overall assessment of disease activity(r=0.318,P=0.036),and the course of psoriatic arthritis(r=0.330,P=0.028).The serum HDAC8 level was positively correlated with HADS score of anxiety(r=0.477,P=0.008)and erythrocyte sedimentation rate(r=0.385,P=0.039).Compared with the patients with low disease activity,those with moderate to high disease activity presented up-regulated expression of HDAC3(P=0.041).HDAC2(P=0.028)and CRP(P=0.034)were risk factors for moderate to high disease activity in PsA patients.HDAC2(area under the curve=0.802,P=0.003)and CRP(area under the curve=0.718,P=0.033)had diagnostic value for the progression of PsA.Conclusions The expression levels of class Ⅰ HDAC in the serum of patients with newly diagnosed PsA were significantly different.The serum levels of HDAC2 and CRP are expected to become serological indicators for the early diagnosis and disease activity assessment of PsA.
Humans
;
Histone Deacetylases/blood*
;
Arthritis, Psoriatic/diagnosis*
;
Male
;
Female
;
Histone Deacetylase 1/blood*
;
Histone Deacetylase 2/blood*
;
Adult
;
Middle Aged
;
Clinical Relevance
;
Repressor Proteins
10.Preparation of doxorubicin-loaded polyphyllin H liposomes and synergistic anti-tumor activity against non-small cell lung cancer in vitro
Yining LIU ; Dawei ZHOU ; Shouchang GAI ; Lu SUI ; Xue SUN ; Zhenhua TONG ; Yuhang WANG ; Jing ZHAO ; Xiaofeng YUAN ; Yong XIANG
Journal of Army Medical University 2025;47(17):2134-2144,封3
Objective To prepare glucose transporter 1(Glut1)-targeted doxorubicin(DOX)-loaded liposomes(doxorubicin/polyphyllin H-liposomes,DOX/ppH-LPs)using polyphyllin H(ppH)instead of cholesterol as the liposomal membrane material,and to investigate their in vitro synergistic anti-tumor activity against non-small cell lung cancer(NSCLC).Methods DOX/ppH-LPs were prepared using thin-film hydration,and the formulation was optimized by single-factor investigation.The optimized DOX/ppH-LPs were characterized for morphology,particle size,polydispersity index(PDI),and zeta potential with transmission electron microscopy(TEM)and dynamic light scattering(DLS).Drug loading DL%was determined by high-performance liquid chromatography(HPLC).The storage stability was evaluated by observing in PBS at 4℃for 7 d,and the serum stability was observed in DMEM containing 10%fetal bovine serum(FBS)at 37℃for 48 h.In vitro drug release was studied in PBS at pH 7.4 and pH 5.0 values,respectively.Human NSCLC A549 cells were subjected as the model,MTT assay was performed to detect the proliferation inhibition by DOX/ppH-LPs at different concentrations(0.5,5.0,15.0 μg/mL)and the control group(ppH+DOX/LPs,a physical mixture of free ppH and DOX-loaded liposomes).Fluorescence microscopy was used to observe cellular uptake of DOX/ppH-LPs and DOX/LPs(containing 5 μg/mL DOX)at 15 min and 2 h.Live/dead cell staining was applied to assess apoptosis/necrosis induced by formulations(15 μg/mL DOX)after 48 h incubation.Transwell assay was conducted to evaluate inhibitory effect on cell migration and invasion,and the targeting property and in vitro synergistic anti-NSCLC activity of DOX/ppH-LPs were then comprehensively evaluated.Results The optimal formulation of DOX/ppH-LPs was determined as hydration temperature at 50℃,6 mg DOX,2 mg ppH,and 24 mg lecithin.The prepared DOX/ppH-LPs were in spherical shape,uniform distribution,and at an average particle size of 145.13±22.14 nm,a PDI of 0.15±0.05,a zeta potential of-23.92±1.73 mV,and a DL of 10.13±0.71%for DOX and(1.22±0.21)%for ppH.DOX/ppH-LPs maintained stable particle size,PDI,and exhibited significantly unchanged zeta potential after storage in PBS at 4℃for 7 d or incubation in DMEM containing 10%FBS at 37℃for 48 h,demonstrating excellent physical and serum stability.Both liposomes showed slow release at pH 7.4 value,while drug release was significantly accelerated at pH 5.0 value(P<0.05),indicating pH-sensitive release characteristics.MTT assay revealed that DOX/ppH-LPs exerted significantly stronger cytotoxicity against A549 cells than the ppH+DOX/LPs control group(P<0.05).Compared with ppH+DOX/LPs,DOX/ppH-LPs showed remarkably enhanced cellular uptake in A549 cells(P<0.05),with more DOX localized in the nucleus.Live/dead cell staining showed that at the same DOX concentration(15 μg/mL),the proportion of apoptotic/necrotic cells induced by DOX/ppH-LPs was significantly higher than that of the DOX/LPs control group.Transwell assay demonstrated that there were significantly less cells migrating and invading through the membrane in the DOX/ppH-LPs group than the ppH+DOX/LPs group.Conclusion Glut1-targeted doxorubicin-loaded liposomes(DOX/ppH-LPs)constructed by substituting cholesterol with ppH can target NSCLC cells,significantly enhance the in vitro synergistic anti-NSCLC activity of DOX and ppH.

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