1.Anti-tumor effect of metal ion-mediated natural small molecules carrier-free hydrogel combined with CDT/PDT.
Wen-Min PI ; Gen LI ; Xin-Ru TAN ; Zhi-Xia WANG ; Xiao-Yu LIN ; Hai-Ling QIU ; Fu-Hao CHU ; Bo WANG ; Peng-Long WANG
China Journal of Chinese Materia Medica 2025;50(7):1770-1780
Metal ion-promoted chemodynamic therapy(CDT) combined with photodynamic therapy(PDT) offers broad application prospects for enhancing anti-tumor effects. In this study, glycyrrhizic acid(GA), copper ions(Cu~(2+)), and norcantharidin(NCTD) were co-assembled to successfully prepare a natural small-molecule, carrier-free hydrogel(NCTD Gel) with excellent material properties. Under 808 nm laser irradiation, NCTD Gel responded to the tumor microenvironment(TME) and acted as an efficient Fenton reagent and photosensitizer, catalyzing the conversion of endogenous hydrogen peroxide(H_2O_2) within the tumor into oxygen(O_2), and hydroxyl radicals(·OH, type Ⅰ reactive oxygen species) and singlet oxygen(~1O_2, type Ⅱ reactive oxygen species), while depleting glutathione(GSH) to stabilize reactive oxygen species and alleviate tumor hypoxia. In vitro and in vivo experiments demonstrated that NCTD Gel exhibited significant CDT/PDT synergistic therapeutic effects. Further safety evaluation and metabolic testing confirmed its good biocompatibility and safety. This novel hydrogel is not only simple to prepare, safe, and cost-effective but also holds great potential for clinical transformation, providing insights and references for the research and development of metal ion-mediated hydrogel-based anti-tumor therapies.
Hydrogels/chemistry*
;
Animals
;
Photochemotherapy
;
Humans
;
Mice
;
Antineoplastic Agents/administration & dosage*
;
Photosensitizing Agents/chemistry*
;
Neoplasms/metabolism*
;
Female
;
Copper/chemistry*
;
Reactive Oxygen Species/metabolism*
;
Tumor Microenvironment/drug effects*
;
Cell Line, Tumor
;
Male
2. Curcumin plays an anti-osteoporosis role by inhibiting NF-κB signaling pathway to reduce oxidative stress damage to osteogenesis
Tian-Tian XU ; Hao-Ehun TIAN ; Xin-Min YANG ; Qi-Hua QI ; Dong-Hua LUO ; Chang-Gen WANG
Chinese Pharmacological Bulletin 2024;40(1):46-54
Aim To investigate the mechanism of curcumin inhibition of oxidative stress on osteogenic differentiation and its dose-dependent anti-osteoporosis effect. Methods Cellular oxidative stress models were used, different concentrations of curcumin were added to determinethebone formation markers, and the potential signaling pathways involvedwere detected. Meanwhile, the mouse model of osteoporosis ( ovariecto- mized, 0VX) was used to confirm its effect against osteoporosis. Results In vitro experiments found that low concentrations of curcumin (1-10 μmol · L
3.Correlation of CD200-CD200R axis and diseases and its research progress
Han XU ; Yu-xin BI ; Gui-xia LI ; Jian LI ; Liu-li WANG ; Rui-jia HAO ; Xue-min ZHENG ; Rui-jing HUANG ; Jin HAN ; Fei LI ; Gen-bei WANG
Acta Pharmaceutica Sinica 2024;59(4):822-830
CD200 and its receptor CD200R constitute an endogenous inhibitory signal. The binding of CD200 and CD200R can regulate the immune response to pathogenic stimuli, which has received much attention in recent years. It has been found that CD200-CD200R is involved in the regulation of many kinds of pathological inflammation, including autoimmune diseases, cardiac cerebrovascular disease, infection and tumor. This paper reviews the protein structure, distribution, expression, biological function of CD200-CD200R and the correlation with diseases, and analyses the current status and development ideas of CD200-CD200R as drug targets. It aims to provide theoretical support for new drug research and development based on this target.
4.Efficacy analysis of 125I seeds implantation combined with transcatheter arterial chemoembolization therapy for primary liver cancer
Wenwen ZHANG ; Shanhu HAO ; Zhiguo WANG ; Liqiu JI ; Gen LI ; Youchao WANG ; Xiangyan GE ; Guoxu ZHANG
Chinese Journal of Nuclear Medicine and Molecular Imaging 2024;44(1):16-19
Objective:To explore the clinical efficacy of 125I seeds implantation combined with transcatheter arterial chemoembolization (TACE) in the treatment of primary liver cancer. Methods:A retrospective analysis of data from 40 patients with primary liver cancer at the Northern Theater General Hospital from January 2018 to December 2020 (26 males, 14 females, age 41 to 82 years) was performed. Among them, 21 patients were in treatment group and underwent 125I seeds implantation combined with TACE treatment, while 19 patients were in control group and received TACE treatment. Alpha-fetoprotein (AFP) levels between the two groups were compared, effective rate and disease control rate (DCR) of the two groups were analyzed, and overall survival (OS) and progression-free survival (PFS) were observed. Data were analyzed by using Mann-Whitney U test, χ2 test, Kaplan-Meier method and log-rank test. Results:Two months after 125I seeds implantation, the effective rates of treatment group and control group were 76.19%(16/21) and 8/19, respectively ( χ2=4.83, P=0.028); the DCRs were 90.48%(19/21) and 11/19, respectively ( χ2=4.21, P=0.040). AFP levels in both groups decreased significantly, with treatment group showing a greater decrease rate (0.87(0.84, 0.90) and 0.66(0.65, 0.67); z=5.42, P<0.001). No serious adverse reaction was observed in either group. The median OS of treatment group and control group were 18.2 and 10.6 months, respectively ( χ2=10.98, P=0.037); the median PFS of the two groups were 8.4 and 6.1 months, respectively ( χ2=7.54, P=0.041). Conclusion:125I seeds implantation combined with TACE treatment can exert a synergistic and enhancing effect in the treatment of primary liver cancer.
5.Sertraline hydrochloride combined with compound chamomile lidocaine gel for the treatment of premature ejaculation
Shu-Gen LI ; Shang GAO ; Zhen-Wei GU ; Dao-Hua ZHAO ; Jie JIANG ; Xiao-Ting LU ; Lan-Xiang LIU ; Hao-Ran LIU ; Ze CHEN
National Journal of Andrology 2024;30(9):809-812
Objective:To investigate the effect of sertraline hydrochloride combined with compound chamomile lidocaine gel in the treatment of premature ejaculation(PE).Methods:We selected 80 cases of PE treated in our hospital from June 2021 to May 2023 and equally randomized them into a control and an observation group,the former medicated with compound chamomile lidocaine gel while the latter with sertraline hydrochloride in addition,both for 6 weeks.We recorded and compared the intravaginal ejaculation latency time(IELT),the number of successful sexual intercourses per week,the Premature Ejaculation Diagnostic Tool(PEDT)scores,and the incidence of adverse reactions between the two groups of patients.Results:After the treatment,the IELT was signif-icantly longer([5.39±1.17]vs[2.49±0.73]min,P<0.05),the weekly number of successful sexual intercourses remarkably higher(1.82±0.45 vs 0.93±0.19,P<0.05)and the PEDT scores markedly lower(7.42±2.04 vs 9.85±2.36,P<0.05)in the observation than in the control group,but no statistically significant differences were observed in the baseline PEDT scores or the incidence of adverse reactions between the two groups(P>0.05).Conclusion:Sertraline hydrochloride combined with com-pound chamomile lidocaine gel is definitely effective in the treatment of PE,which can significantly improve the patients'quality of sexual life,with a high safety and low incidence of adverse reactions.
6.Diagnostic performance of PI-RADS v2.1 for clinically significant prostate cancer in the peripheral,transitional and multiple zones
Xiao-Jun DENG ; Hao-Cheng ZHANG ; Jiong ZHANG ; Yu-Hang QIAN ; Mei-Mei TAO ; Chun-Mei LIAO ; Miao-Wen LIN ; Gen-Qiang LANG
National Journal of Andrology 2024;30(11):982-986
Objective:To evaluate the diagnostic performance of the Prostate Imaging Reporting and Data System version 2.1(PI-RADS v2.1)for clinically significant prostate cancer(CSPCa)in the peripheral zone(PZ),transitional zone(TZ)and multiple zones(MZs).Methods:We retrospectively studied the clinical data on 108 patients undergoing multiparametric magnetic resonance imaging(mpMRI)and transperineal prostate biopsy in our hospital from January 2021 to January 2023.Using PI-RADS v2.1,we ex-amined the MR images of the patients with suspected PCa,compared the PI-RADS v2.1 scores with the results of prostate biopsy,and analyzed the correlation of the PI-RADS v2.1 scores with CSPCa.We calculated the area under the receiver operating characteristic(ROC)curve(AUC),and described the diagnostic performance of PI-RADS v2.1 for CSPCa in the PZ,TZ and MZs.Results:Transperineal prostate puncture biopsy was successfully completed in all the patients,which revealed 66(61.11%)cases of CSPCa with Gleason score(GS)7-10.Suspected CSPCa was observed in 45(95.74%)of the 47 PZ lesions,8(47.06%)of the 17 TZ le-sions,and 40(90.91%)of the 44 MZ lesions.The PZ,TZ and MZ lesions diagnosed by PI-RADS v2.1 were significantly correlated with CSPCa(r=0.492,P<0.001).The AUCs of PI-RADS v2.1 for PZ,TZ and MZs were 0.644,0.732 and 0.811,with specificities of 66.8%,57.6%and 62.1%,and sensitivities of 57.2%,78.4%and 93.2%,respectively.The negative predictive values were 46.5%,85.7%and 79.2%,and the positive predictive values 76.2%,43.4%and 84.8%,respectively.Conclusion:The PI-RADS v2.1 score has a high diagnostic value for CSPCa in the PZ,TZ and MZs,with the best performance for that in the MZs.
7.Long-term therapeutic efficacy and prognosis analysis of complex high-risk coronary heart disease patients undergoing elective percutaneous coronary intervention with extracorporeal membrane oxygenation combined with intra-aortic balloon pump
Tian-Tong YU ; Shuai ZHAO ; Yan CHEN ; You-Hu CHEN ; Gen-Rui CHEN ; Huan WANG ; Bo-Hui ZHANG ; Xi ZHANG ; Bo-Da ZHU ; Peng HAN ; Hao-Kao GAO ; Kun LIAN ; Cheng-Xiang LI
Chinese Journal of Interventional Cardiology 2024;32(9):501-508
Objective We aimed to compare the efficacy and prognosis of percutaneous coronary intervention(PCI)in complex and high-risk patients with coronary heart disease(CHD)treated with extracorporeal membrane oxygenation(ECMO)combined with intra-aortic balloon pump(IABP)assistance,and explore the application value of combined use of mechanical circulatory support(MCS)devices in complex PCI.Methods A total of patients who met the inclusion criteria and underwent selective PCI supported by MCS at the Department of Cardiology,the First Affiliated Hospital of the Air Force Medical University from January 2018 to December 2022 were continuously enrolled.According to the mechanical circulatory support method,the patients were divided into ECMO+IABP group and IABP group.Clinical characteristics,angiographic features,in-hospital outcomes,and complications were collected.The intra-hospital outcomes and major adverse cardiovascular events(MACE)at one month and one year after the procedure were observed.The differences and independent risk factors between the two groups in the above indicators were analyzed.Results A total of 218 patients undergoing elective PCI were included,of which 66 patients were in the ECMO+IABP group and 152 patients were in the IABP group.The baseline characteristics of the two groups of patients were generally comparable,but the ECMO+IABP group had more complex lesion characteristics.The proportion of patients with atrial fibrillation(6.1%vs.0.7%,P=0.030),left main disease(43.9%vs.27.0%,P=0.018),triple vessel disease(90.9%vs.75.5%,P=0.009),and RCA chronic total occlusion disease(60.6%vs.35.5%,P<0.001)was higher in the ECMO+IABP group compared to the IABP group.The proportion of patients with previous PCI history was higher in the IABP group(32.9%vs.16.7%,P=0.014).There was no statistically significant difference in the incidence of in-hospital complications between the two groups(P=0.176),but the incidence of hypotension after PCI was higher in the ECMO+IABP group(19.7%vs.9.2%,P=0.031).The rates of 1-month MACE(4.5%vs.2.6%,P=0.435)and 1-year MACE(7.6%vs.7.9%,P=0.936)were comparable between the two groups.Multivariate analysis showed that in-hospital cardiac arrest(OR 7.17,95%CI 1.27-40.38,P=0.025)and after procedure hypotension(OR 3.60,95%CI 1.10-11.83,P=0.035)were independent risk factors for the occurrence of 1-year MACE.Conclusions Combination use of ECMO+IABP support can provide complex and high-risk coronary heart disease patients with an opportunity to achieve coronary artery revascularization through PCI,and achieve satisfactory long-term prognosis.
8.Astragalus polysaccharides induces ferroptosis in ovarian adenocarcinoma cells through Nrf2/SLC7A11/GPX4 signaling pathway.
Yong-Gen ZHANG ; Xiao-Fei YAN ; Feng LIU ; Wen-Zhe HAO ; Yue CAI ; Ying LIU ; Lan-Lin LIU ; Xue-Jun LI
China Journal of Chinese Materia Medica 2024;49(23):6459-6467
This study primarily investigated the mechanism of Astragalus polysaccharides(APS), a Chinese medicinal material, in regulating the Nrf2/SLC7A11/GPX4 signaling pathway to induce ferroptosis in ovarian cancer cells(Caov-3 and SKOV3 cells). Caov-3 and SKOV3 cells were divided into control(Vehicle) group, APS group, glutathione peroxidase 4 inhibitor(RSL3) group, and APS+RSL3 group. After 48 h of intervention, the activity and morphology of the cells in each group were observed. The cell counting kit-8(CCK-8) method was used to determine the half-maximal inhibitory concentration(IC_(50)), while colony formation and EdU assays were conducted to assess cell proliferation. Biochemical reagents were used to detect lipid reactive oxygen species(L-ROS), malondialdehyde(MDA), divalent iron ions(Fe~(2+)), and glutathione(GSH) in Caov-3 cells. Transmission electron microscopy was employed to observe the morphological changes of mitochondria in Caov-3 cells. Bioinformatics analysis were used to screen potential target genes of APS in ovarian cancer cells. Western blot and RT-PCR were applied to measure the protein and mRNA expression of Nrf2, SLC7A11, and GPX4. The results revealed that APS effectively inhibited the activity and proliferation of ovarian cancer cells, significantly increased the expression levels of L-ROS, MDA, and Fe~(2+)(P<0.001), and significantly reduced the expression level of GSH(P<0.001). Under electron microscopy, the mitochondria of Caov-3 cells appeared significantly smaller, with a marked increase in the density of the bilayer membrane, disappearance of mitochondrial cristae, and rupture of the outer mitochondrial membrane. These effects were more pronounced when APS was combined with RSL3. Bioinformatics screening identified Nrf2, SLC7A11, and GPX4 as potential target genes for APS in ovarian cancer cells. APS was shown to reduce the protein and mRNA expression of Nrf2, SLC7A11, and GPX4(P<0.01), with the APS+RSL3 showing even more significant effects(P<0.001). In conclusion, APS can induce ferroptosis in ovarian cancer cells, and its mechanism may be related to the regulation of the Nrf2/SLC7A11/GPX4 signaling pathway, providing an experimental basis for the use of APS injections in the treatment of ovarian cancer.
Humans
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Ferroptosis/drug effects*
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Female
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NF-E2-Related Factor 2/genetics*
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Ovarian Neoplasms/physiopathology*
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Phospholipid Hydroperoxide Glutathione Peroxidase/genetics*
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Signal Transduction/drug effects*
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Cell Line, Tumor
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Amino Acid Transport System y+/genetics*
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Polysaccharides/pharmacology*
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Astragalus Plant/chemistry*
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Drugs, Chinese Herbal/pharmacology*
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Adenocarcinoma/physiopathology*
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Cell Proliferation/drug effects*
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Glutathione Peroxidase/genetics*
;
Reactive Oxygen Species/metabolism*
9.Research progress in site mutations of SARS-CoV-2 Omicron variants
Gen MIAO ; Zhiwei HE ; Yibo CHEN ; Cuiling DING ; Hao REN ; Ping ZHAO ; Zhongtian QI
Chinese Journal of Microbiology and Immunology 2023;43(3):173-181
SARS-CoV-2 Omicron variant (B.1.1.529) was first discovered in South Africa in November 2021 and has since become a mainstream strain worldwide. Omicron variant was defined as the fifth "variant of concern (VOC)" by World Health Organization on November 26, 2021. This paper illustrates the mutation trends of Omicron variants in terms of SARS-CoV-2 genome and protein structure as well as nucleic acid site mutations and amino acid site mutations, describes the features of Omicron mutation sites in terms of lineage comparison among the VOCs and Omicron sublineages, and further highlights the influences of Omicron site mutations from the aspects of immune escape, virulence and transmission ability. Moreover, this paper also reviews the development of direct antiviral agents, antibodies and vaccines, aiming to provide reference for further investigation.
10.Triterpenoids from an aqueous extract of the Ziziphus jujuba var. spinosa seeds
Wen-sa HAO ; Cheng-gen ZHU ; Xiao-qiang LEI ; Cheng-bo XU ; Qing-lan GUO ; Jian-gong SHI
Acta Pharmaceutica Sinica 2023;58(9):2734-2745
Four new triterpenoids, together with six known analogues, were isolated from an aqueous extract of the

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