Cantharidin (CTD), a natural compound used to treat multiple tumors in the clinic setting, has been limited due to acute kidney injury (AKI). However, the major cause of AKI and its underlying mechanism remain to be e...Cantharidin (CTD), a natural compound used to treat multiple tumors in the clinic setting, has been limited due to acute kidney injury (AKI). However, the major cause of AKI and its underlying mechanism remain to be elucidated. Serum creatinine (SCr) and blood urea nitrogen (BUN) were detected through pathological evaluation after CTD (1.5 mg/kg) oral gavage in mice in 3 days. Kidney lipidomics based on ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to investigate lipids disorder after CTD exposure in mice. Then, spatial metabolomics based on matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) was used to detect the kidney spatial distribution of lipids. Integrative analysis was performed to reveal the spatial lipid disorder mechanism and verify key lipids in vitro. The results showed that the levels of SCr and BUN were increased, and tubular necrosis was observed in mouse kidneys, resulting in acute tubular necrosis (ATN) in CTD-induced AKI. Then, lipidomics results revealed that after CTD exposure, 232 differential lipid metabolites and 11 pathways including glycerophospholipid (GP) and sphingolipid (SL) metabolism were disrupted. Spatial metabolomics revealed that 55 spatial differential lipid metabolites and nine metabolic pathways were disturbed. Subsequently, integrative analysis found that GP metabolism was stimulated in the renal cortex and medulla, whereas SL metabolism was inhibited in the renal cortex. Up-regulated lysophosphatidylcholine (LysoPC) (18:2(9Z,12Z)), LysoPC (16:0/0:0), glycerophosphocholine, and down-regulated sphingomyelin (SM) (d18:0/16:0), SM (d18:1/24:0), and SM (d42:1) were key differential lipids. Among them, LysoPC (16:0/0:0) was increased in the CTD group at 1.1196 μg/mL, which aggravated CTD-induced ATN in human kidney-2 (HK-2) cells. LysoPC acyltransferase was inhibited and choline phosphotransferase 1 (CEPT1) was activated after CTD intervention in mice and in HK-2 cells. CTD induces ATN, resulting in AKI, by activating GP metabolism and inhibiting SL metabolism in the renal cortex and medulla, LysoPC (16:0/0:0), LysoPC acyltransferase, and CEPT1 may be the therapeutic targets.展开更多
A series of 1,2-cyclic monoacyl-rac-glycerothiophosphates of cantharidin and its analogues were synthesized in a one-pot procedure in overall yields of 44 similar to 55.5% by means of hexaethylphosphorus triamide as p...A series of 1,2-cyclic monoacyl-rac-glycerothiophosphates of cantharidin and its analogues were synthesized in a one-pot procedure in overall yields of 44 similar to 55.5% by means of hexaethylphosphorus triamide as phosphorylating reagent.展开更多
Objective： To study the inhibition of Cantharidin against the proliferation of human lung cancer A549 cells and its mechanism. Methods： MTT assay was employed to determine the inhibition of Cantharidin against proli...Objective： To study the inhibition of Cantharidin against the proliferation of human lung cancer A549 cells and its mechanism. Methods： MTT assay was employed to determine the inhibition of Cantharidin against proliferation of A549 cells and flow Cytometry was applied to analyze A549 cell cycle and the effect of Cantharidin on cell cycle. Results： Cantharidin showed inhibition against the proliferation of A549 cells, and the inhibition was mediated by blocking A549 cell cycle at G2/M phase significantly. Conclusion： Cantharidin exhibits inhibition against the proliferation of human lung cancer A549 cells.展开更多
BACKGROUND This report delves into the diagnostic and therapeutic journey undertaken by a patient with high-dose cantharidin poisoning and multiorgan dysfunction syndrome(MODS).Particular emphasis is placed on the com...BACKGROUND This report delves into the diagnostic and therapeutic journey undertaken by a patient with high-dose cantharidin poisoning and multiorgan dysfunction syndrome(MODS).Particular emphasis is placed on the comprehensive elucidation of the clinical manifestations of high-dose cantharidin poisoning,the intricate path to diagnosis,and the exploration of potential underlying mechanisms.CASE SUMMARY A patient taking 10 g of cantharidin powder orally subsequently developed MODS.The patient was treated with supportive care,fluid hydration and antibiotics,and hemoperfusion and hemofiltration therapy for 24 h and successfully recovered 8 d after hospital admission.Cantharidin poisoning can cause lifethreatening MODS and is rare clinically.This case underscores the challenge in diagnosis and highlights the need for early clinical differentiation to facilitate accurate assessment and prompt intervention.CONCLUSION This article has reported and analyzed the clinical data,diagnosis,treatment,and prognosis of a case of high-dose cantharidin poisoning resulting in MODS and reviewed the relevant literature to improve the clinical understanding of this rare condition.展开更多
Background:Cantharidin (CTD),a natural toxin produced from Chinese blister beetles,has extensive anti-tumor activity.The present study investigated the effect of CTD on a human colon cancer cell line to elucidate pote...Background:Cantharidin (CTD),a natural toxin produced from Chinese blister beetles,has extensive anti-tumor activity.The present study investigated the effect of CTD on a human colon cancer cell line to elucidate potential new insights regarding the mechanism(s) through which CTD exerts its anti-tumor effects.Materials and methods:The inhibitory effect of CTD on human colon cancer HCT116 cells was evaluated using the IncuCyte ZOOMTM analyzer.Apoptotic cells were detected by Annexin V-FITC/PI assay and cell cycle was evaluated with flow cytometry following propidium iodide staining.Alterations in F-actin microfilaments were analyzed by FITC-phalloidin staining and morphological changes were evaluated with a laser scanning confocal microscope.Cell migration assay was carried out to investigate the effects of CTD on migration of HCT116 cells in vitro.Results:CTD exhibited a significant growth inhibitory effect on HCT116 cells accompanied by an increase in G2/M phase cells,without a significant effect on apoptosis.CTD-treated cells also exhibited a dramatic collapse in their microfilament network and a significant reduction in cell adhesion.Conclusion:CTD inhibits growth by increasing G2/M phase cells and decreasing S phase cells,revealing that CTD exerts a significant growth inhibitory effect primarily through an inhibition of cell cycle progression (a cytostatic effect).Moreover,a negative effect on cell migration may also constitute a contributing factor to its anti-tumor potential.These findings suggest the potential use for developing CTD as a novel anti-cancer therapy that targets metastasis Giving full play to CTD may inhibit tumor transfer.展开更多
Background:Cantharidin is a major active compound from Banmao(Mylabris).Cantharidin has obvious anticancer activity.However,its clinical application is limited due to serious hepatotoxicity.Methods:To evaluate the tox...Background:Cantharidin is a major active compound from Banmao(Mylabris).Cantharidin has obvious anticancer activity.However,its clinical application is limited due to serious hepatotoxicity.Methods:To evaluate the toxicity of human liver LO2 cells exposed to cantharidin by lipidomics.After exposing LO2 cells to different doses of cantharidin,the metabolites in LO2 cells were analyzed by nontargeted lipidomics based on liquid chromatography-mass spectrometry.Partial least-squares discriminant analysis and orthogonal partial least-squares discriminant analysis were used to screen differentially expressed metabolites,and then the main metabolic pathways were analyzed.Results:Pattern recognition analysis showed that the lipid metabolite profiles were changed significantly after cantharidin treatment,and 39 differential lipid metabolites were found.Additional analysis showed that these metabolites could mainly involve the metabolic pathways of triglyceride and acylcarnitine for cantharidin toxicity to LO2 cells.Conclusion:Cantharidin has obvious toxic effects on LO2 cells from the perspective of lipid metabolism.Moreover,the LO2 cytotoxicity induced by cantharidin is mainly related to the disorder of triglyceride and acylcarnitine metabolism.It can provide a scientific basis for cantharidin-induced hepatotoxicity.展开更多
Background:Cantharidin(CTD)is a commonly used natural product with anticancer properties;however,it has significant adverse effects,particularly hepatotoxicity.Glycyrrhetinic acid(GA),the active component of licorice,...Background:Cantharidin(CTD)is a commonly used natural product with anticancer properties;however,it has significant adverse effects,particularly hepatotoxicity.Glycyrrhetinic acid(GA),the active component of licorice,shows potential hepatoprotective effects.The protective effects and mechanism of GA against CTD-induced hepatotoxicity are still unclear.Objective:This study aims to elucidate the effect and mechanism of GA on CTD-induced hepatotoxicity in mice experiments.Methods:Construction of CTD-induced hepatotoxicity models and oral gavage GA intervention for 14 d.The liver index,ALT,AST and LDH levels in the serum of the mice were examined;HE staining was performed to observe pathological changes in the liver.The MDA level and SOD activities in liver tissue were tested.Western blot was conducted to determine Keap1/Nrf2 signaling pathway-related protein expression.Results:The results showed that GA significantly reduced the levels of ALT,AST,and LDH in the serum,which were increased by CTD.Additionally,it also exerted a substantial inhibitory effect on the reduction of SOD activity and the elevation of malondialdehyde content in liver tissue.Notably,the phenomena of nuclear swelling,necrosis,and inflammatory infiltration of liver tissue were significantly attenuated following oral administration of GA in mice.Subsequent research has demonstrated that GA effectively suppressed the CTD-triggered upregulation of Keap1 while increasing the CTD-induced downregulation of Nrf2,HO-1,and NQO1.Conclusion:These findings suggested that GA may protect against CTD-induced hepatotoxicity in mice by exerting antioxidative stress through the Keap1/Nrf2 signaling pathway.展开更多
目的基于细胞药动学探究斑蝥素与黄芩苷配伍在亚细胞水平的分布规律,阐明其抗肝癌的增效机制。方法以人肝癌HepG2细胞为模型,采用超高效液相色谱-串联质谱(ultra-high performance liquid chromatography-tandem mass spectrometry,UPLC...目的基于细胞药动学探究斑蝥素与黄芩苷配伍在亚细胞水平的分布规律,阐明其抗肝癌的增效机制。方法以人肝癌HepG2细胞为模型,采用超高效液相色谱-串联质谱(ultra-high performance liquid chromatography-tandem mass spectrometry,UPLC-MS/MS)定量分析单药(斑蝥素6μg/mL、黄芩苷30μg/mL)及配伍组(斑蝥素6μg/mL+黄芩苷30μg/mL)给药后12 h内,整体细胞及细胞核、线粒体、内质网和溶酶体各细胞器中药物浓度的动态变化,并应用Phoenix WinNonlin软件非房室模型计算药动学参数。结果在整体细胞水平,配伍使斑蝥素的胞内药时曲线下面积(area under the curve,AUC_(0~t))增加48.9%,清除率降低(P<0.05),但未显著影响黄芩苷的药动学行为。在亚细胞层面,配伍使斑蝥素与黄芩苷在细胞核、溶酶体、线粒体、内质网内的AUC_(0~t)分别增加了93.5%、46.4%、38.3%、52.3%和68.4%、40.0%、41.0%、46.7%(P<0.05、0.01)。此外,配伍后2种药物在线粒体内达峰时间(t_(max))提前,且斑蝥素在内质网中的平均驻留时间(mean residence time,MRT_(0~t))显著延长(P<0.01),表明两者配伍实现了时空协同的药物递送。结论斑蝥素/黄芩苷配伍可通过协同优化药物在细胞核、线粒体、内质网及溶酶体等关键亚细胞结构的分布,进而可能通过诱导DNA损伤、加速线粒体介导细胞凋亡及促进内质网应激等途径,增强抗肝癌效果,为基于细胞器靶向的中药配伍设计提供了理论依据。展开更多
Objective To increase the solubility and relieve the mucous irritation of cantharidin (CA) by preparing cantharidin-hydroxypropyl-β-cyclodextrin (CA/HP-β-CD) inclusion complex. Methods The inclusion complex was prep...Objective To increase the solubility and relieve the mucous irritation of cantharidin (CA) by preparing cantharidin-hydroxypropyl-β-cyclodextrin (CA/HP-β-CD) inclusion complex. Methods The inclusion complex was prepared by co-evaporation method and characterized by differential scanning calorimetry (DSC), X-ray diffractometry (XRD), and nuclear magnetic resonance (NMR). Results The disappearance of CA as well as the shift of exothermic peaks shown in DSC results indicated the complexation phenomenon. XRD results showed that the crystalline CA pattern had disappeared, and in NMR results, H-5 shifted from δ 3.731 to 3.695 after complexation and H-2 shifted from δ 3.626 to 3.598, which suggested that part of the drug had entered the HP-β-CD cavity to form an inclusion complex. The solubility increased 10.3 times after complexation and the mucous irritation of CA was relieved remarkably. Conclusion Through complexation with HP-β-CD, the solubility and dissolution rate of CA are improved significantly, and the irritation of musous is relieved.展开更多
Transcatheter arterial embolization with hydroxycamptothecine, cantharidin and cisplatin,thoroughly mixed with large doses of interferon and interleukin-2, was performed in 48 cases with unre-sectable intermediate or ...Transcatheter arterial embolization with hydroxycamptothecine, cantharidin and cisplatin,thoroughly mixed with large doses of interferon and interleukin-2, was performed in 48 cases with unre-sectable intermediate or advanced hepatocellular carcinoma. The results demonstrate a partial remissionrate of 54. 2%, significantly higher than that in embolization with chemotherapeutic agents alone (cis-platin, adriamycin and mitomycin, 32. 1%, P<O. 01) . Morever, the adverse reactions of hydroxycamp-tothecine and cantharidin, when applied systemically, including hematuria or urodynia were successfullyeliminated.展开更多
目的探讨斑蝥素(Cantharidin)对结直肠癌SW480细胞增殖、侵袭及凋亡的影响,并初步阐明其潜在分子机制。方法采用体外培养的SW480细胞,通过MTS法和克隆形成实验检测细胞活力与长期增殖能力;利用Transwell实验评估细胞侵袭能力;运用流式...目的探讨斑蝥素(Cantharidin)对结直肠癌SW480细胞增殖、侵袭及凋亡的影响,并初步阐明其潜在分子机制。方法采用体外培养的SW480细胞,通过MTS法和克隆形成实验检测细胞活力与长期增殖能力;利用Transwell实验评估细胞侵袭能力;运用流式细胞术分析细胞凋亡与周期分布;并采用Western Blot技术检测PI3K/AKT信号通路关键蛋白的表达及其磷酸化水平。结果与对照组相比,斑蝥素能够剂量依赖性地显著抑制SW480细胞的增殖(48 h IC_(50)为11.63μM)、克隆形成及侵袭能力。此外,斑蝥素可诱导细胞周期阻滞于G2/M期,并显著促进细胞凋亡。研究表明,斑蝥素处理能显著抑制PI3K与AKT的磷酸化,下调总PI3K、总AKT、CDK4、MMP9及抗凋亡蛋白Bcl-2的表达,同时上调促凋亡蛋白Bax的表达。结论斑蝥素可通过抑制PI3K/AKT信号通路,进而抑制结直肠癌SW480细胞的增殖与侵袭,并诱导其凋亡。展开更多
Blister beetles(Coleoptera:Meloidae)produce a natural defensive toxin cantharidin(CTD),which has been used for various cancer treatments and other diseases.Currently,the lack of chromosome-level reference genomes in M...Blister beetles(Coleoptera:Meloidae)produce a natural defensive toxin cantharidin(CTD),which has been used for various cancer treatments and other diseases.Currently,the lack of chromosome-level reference genomes in Meloidae limits further understanding of the mechanism of CTD biosynthesis and environmental adaptation.In this study,the chromosome-level genome assembly of Mylabris phalerata was generated based on PacBio and Hi-C sequencing.This reference genome was about 136.68 Mb in size with contig N50 of 9.17 Mb and composed of 12 chromosomes.In comparison to six other Coleoptera insects,M.phalerata exhibited multiple expanded gene families enriched in juvenile hormone(JH)biosynthetic process pathway,farnesol dehydrogenase activity,and cytochrome P450,which may be related to CTD biosynthesis.Consistently,the transcriptomic analysis suggested the“terpenoid backbone biosynthesis”pathway and“the juvenile hormone”as putative core pathways of CTD biosynthesis and presented eight up-regulated differential expression genes in male adults as candidate genes.It is possible that the restricted feeding niche and lifestyle of M.phalerata were the cause of the gene family’s contraction of odorant binding proteins.The ABC transporters(ABCs)related to exporting bound toxins out of the cell and the resistance to the self-secreted toxins(e.g.CTD)were also contracted,possibly due to other self-protection strategies in M.phalerata.A foundation of understanding CTD biosynthesis and environmental adaptation of blister beetles will be established by our reference genome and discoveries.展开更多
目的评价叶酸修饰的斑蝥素/黄芩苷脂质体(DSPE-PEG2k-folate-cantharidin&baicalin@lipsomes,FA-Can&Bai@Lips)在正常大鼠与荷瘤大鼠体内的药动学及组织分布差异。方法以HepG2细胞悬液接种于大鼠右侧腋下诱导荷瘤大鼠模型,尾静...目的评价叶酸修饰的斑蝥素/黄芩苷脂质体(DSPE-PEG2k-folate-cantharidin&baicalin@lipsomes,FA-Can&Bai@Lips)在正常大鼠与荷瘤大鼠体内的药动学及组织分布差异。方法以HepG2细胞悬液接种于大鼠右侧腋下诱导荷瘤大鼠模型,尾静脉注射FA-Can&Bai@Lips后采集不同给药时间点血浆与组织(心、肝、脾、肺、肾),采用超高效液相色谱-串联质谱联用技术(UPLC-MS/MS)测定血浆及组织中斑蝥素和黄芩苷浓度,应用Phoenix WinNonlin软件计算药动学参数,并分析比较FA-Can&Bai@Lips在正常机体状态与荷瘤状态下的药动学和组织分布差异。结果建立的同时测定斑蝥素与黄芩苷的UPLC-MS/MS方法线性关系良好,专属性、准确度与精密度、提取回收率与基质效应及稳定性等均符合生物样本检测要求。药动学参数表明,与正常组大鼠相比,荷瘤大鼠体内斑蝥素与黄芩苷的药时曲线下面积(area under the curve,AUC0-t、AUC0-∞)、平均驻留时间(mean residence time,MRT0-t、MRT0-∞)均显著升高(P<0.05),分别增加了55.68%、72.50%、43.10%、45.95%和15.10%、42.54%、9.09%、10.53%;斑蝥素在荷瘤大鼠体内半衰期(half-life,t1/2)缩短,但无显著性差异,而黄芩苷的t1/2显著延长(P<0.05),两者的表观分布容积(apparent volume of distribution,Vd)与清除率(clearance rate,CL)均明显降低。组织分布结果显示,斑蝥素与黄芩苷在荷瘤大鼠肝脏中浓度明显高于正常大鼠,其余组织药物浓度均显著低于正常大鼠。结论UPLC-MS/MS法分析速度快、简单、特异、灵敏,可用于大鼠血浆及组织中斑蝥素与黄芩苷的测定,且证实荷瘤状态会对FA-Can&Bai@Lips的体内药动学及组织分布产生明显影响。展开更多
目的:制备叶酸修饰的共载斑蝥素和星形孢菌素的脂质体纳米递送体系(folic acid-modified liposomes nanodelivery system co-loaded with cantharidin and staurosporine,FA/CTD-STS/NL),并对其性质进行评价。方法:采用薄膜分散法制备FA...目的:制备叶酸修饰的共载斑蝥素和星形孢菌素的脂质体纳米递送体系(folic acid-modified liposomes nanodelivery system co-loaded with cantharidin and staurosporine,FA/CTD-STS/NL),并对其性质进行评价。方法:采用薄膜分散法制备FA/CTD-STS/NL,用凝胶柱-HPLC法测定脂质体的包封率。用透射电镜(transmission electron microscopy,TEM)观察脂质体的形态,激光粒度分析仪测定脂质体的粒径及其分布、Zeta电势,并考察其血清稳定性、长期稳定性和血液相容性。通过CCK-8法检测其细胞毒性。结果:FA/CTD-STS/NL外观呈类球形,分散均匀。平均粒径、多分散性指数、Zeta电势分别为(114.3±0.9)nm,(0.212±0.018)和-(1.19±0.13)mV,平均包封率分别为(89.62±0.67)%和(96.01±1.02)%。其血清稳定性和长期稳定性良好,溶血率均<5%,说明具有良好的血液相容性。FA/CTD-STS/NL对小鼠正常肝细胞(AML-12细胞)具有良好的细胞相容性。结论:本研究制备的FA/CTD-STS/NL具有良好的稳定性和生物安全性,包封率高,粒径符合抗癌纳米递送载体的要求,有利于药物在肿瘤组织的富集。本研究为后续FA/CTD-STS/NL体内外靶向性、抗肝癌作用及机制研究奠定实验基础。展开更多
基金supported by the National Natural Science Foundation of China(Grant Nos.:82260812 and 81803838)the Guizhou Provincial Science&Technology Program,China(Project Nos.:YQK[2023]038 and[2020]5007)+1 种基金the Beijing Natural Science Foundation,China(Grant No.:7254489)the Science and Technology Program of Zunyi city of Guizhou province of China(Project Nos.:(2022)420,[2021]-3,[2020]7,and(2022)419).
文摘Cantharidin (CTD), a natural compound used to treat multiple tumors in the clinic setting, has been limited due to acute kidney injury (AKI). However, the major cause of AKI and its underlying mechanism remain to be elucidated. Serum creatinine (SCr) and blood urea nitrogen (BUN) were detected through pathological evaluation after CTD (1.5 mg/kg) oral gavage in mice in 3 days. Kidney lipidomics based on ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to investigate lipids disorder after CTD exposure in mice. Then, spatial metabolomics based on matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) was used to detect the kidney spatial distribution of lipids. Integrative analysis was performed to reveal the spatial lipid disorder mechanism and verify key lipids in vitro. The results showed that the levels of SCr and BUN were increased, and tubular necrosis was observed in mouse kidneys, resulting in acute tubular necrosis (ATN) in CTD-induced AKI. Then, lipidomics results revealed that after CTD exposure, 232 differential lipid metabolites and 11 pathways including glycerophospholipid (GP) and sphingolipid (SL) metabolism were disrupted. Spatial metabolomics revealed that 55 spatial differential lipid metabolites and nine metabolic pathways were disturbed. Subsequently, integrative analysis found that GP metabolism was stimulated in the renal cortex and medulla, whereas SL metabolism was inhibited in the renal cortex. Up-regulated lysophosphatidylcholine (LysoPC) (18:2(9Z,12Z)), LysoPC (16:0/0:0), glycerophosphocholine, and down-regulated sphingomyelin (SM) (d18:0/16:0), SM (d18:1/24:0), and SM (d42:1) were key differential lipids. Among them, LysoPC (16:0/0:0) was increased in the CTD group at 1.1196 μg/mL, which aggravated CTD-induced ATN in human kidney-2 (HK-2) cells. LysoPC acyltransferase was inhibited and choline phosphotransferase 1 (CEPT1) was activated after CTD intervention in mice and in HK-2 cells. CTD induces ATN, resulting in AKI, by activating GP metabolism and inhibiting SL metabolism in the renal cortex and medulla, LysoPC (16:0/0:0), LysoPC acyltransferase, and CEPT1 may be the therapeutic targets.
文摘A series of 1,2-cyclic monoacyl-rac-glycerothiophosphates of cantharidin and its analogues were synthesized in a one-pot procedure in overall yields of 44 similar to 55.5% by means of hexaethylphosphorus triamide as phosphorylating reagent.
文摘Objective： To study the inhibition of Cantharidin against the proliferation of human lung cancer A549 cells and its mechanism. Methods： MTT assay was employed to determine the inhibition of Cantharidin against proliferation of A549 cells and flow Cytometry was applied to analyze A549 cell cycle and the effect of Cantharidin on cell cycle. Results： Cantharidin showed inhibition against the proliferation of A549 cells, and the inhibition was mediated by blocking A549 cell cycle at G2/M phase significantly. Conclusion： Cantharidin exhibits inhibition against the proliferation of human lung cancer A549 cells.
基金Supported by Jilin Province Science and Technology Agency Project,No.20210101350JCProject of Jilin Provincial Finance Department,No.JLSWSRCZX2023-60Beijing iGandan Foundation Fund for Artificial Liver,No.iGandanF-1082023-RGG025.
文摘BACKGROUND This report delves into the diagnostic and therapeutic journey undertaken by a patient with high-dose cantharidin poisoning and multiorgan dysfunction syndrome(MODS).Particular emphasis is placed on the comprehensive elucidation of the clinical manifestations of high-dose cantharidin poisoning,the intricate path to diagnosis,and the exploration of potential underlying mechanisms.CASE SUMMARY A patient taking 10 g of cantharidin powder orally subsequently developed MODS.The patient was treated with supportive care,fluid hydration and antibiotics,and hemoperfusion and hemofiltration therapy for 24 h and successfully recovered 8 d after hospital admission.Cantharidin poisoning can cause lifethreatening MODS and is rare clinically.This case underscores the challenge in diagnosis and highlights the need for early clinical differentiation to facilitate accurate assessment and prompt intervention.CONCLUSION This article has reported and analyzed the clinical data,diagnosis,treatment,and prognosis of a case of high-dose cantharidin poisoning resulting in MODS and reviewed the relevant literature to improve the clinical understanding of this rare condition.
文摘Background:Cantharidin (CTD),a natural toxin produced from Chinese blister beetles,has extensive anti-tumor activity.The present study investigated the effect of CTD on a human colon cancer cell line to elucidate potential new insights regarding the mechanism(s) through which CTD exerts its anti-tumor effects.Materials and methods:The inhibitory effect of CTD on human colon cancer HCT116 cells was evaluated using the IncuCyte ZOOMTM analyzer.Apoptotic cells were detected by Annexin V-FITC/PI assay and cell cycle was evaluated with flow cytometry following propidium iodide staining.Alterations in F-actin microfilaments were analyzed by FITC-phalloidin staining and morphological changes were evaluated with a laser scanning confocal microscope.Cell migration assay was carried out to investigate the effects of CTD on migration of HCT116 cells in vitro.Results:CTD exhibited a significant growth inhibitory effect on HCT116 cells accompanied by an increase in G2/M phase cells,without a significant effect on apoptosis.CTD-treated cells also exhibited a dramatic collapse in their microfilament network and a significant reduction in cell adhesion.Conclusion:CTD inhibits growth by increasing G2/M phase cells and decreasing S phase cells,revealing that CTD exerts a significant growth inhibitory effect primarily through an inhibition of cell cycle progression (a cytostatic effect).Moreover,a negative effect on cell migration may also constitute a contributing factor to its anti-tumor potential.These findings suggest the potential use for developing CTD as a novel anti-cancer therapy that targets metastasis Giving full play to CTD may inhibit tumor transfer.
基金The National Natural Science Foundation of China(Grants no.81760746 and 81803838)Education Department of Guizhou Province of China(GNYL[2017]006)+1 种基金Provincial Department of Education youth talent support program(qiankehe KY[2017]078)Guizhou Provincial Science&Technology“125-Plan”Major Project([2015]039).
文摘Background:Cantharidin is a major active compound from Banmao(Mylabris).Cantharidin has obvious anticancer activity.However,its clinical application is limited due to serious hepatotoxicity.Methods:To evaluate the toxicity of human liver LO2 cells exposed to cantharidin by lipidomics.After exposing LO2 cells to different doses of cantharidin,the metabolites in LO2 cells were analyzed by nontargeted lipidomics based on liquid chromatography-mass spectrometry.Partial least-squares discriminant analysis and orthogonal partial least-squares discriminant analysis were used to screen differentially expressed metabolites,and then the main metabolic pathways were analyzed.Results:Pattern recognition analysis showed that the lipid metabolite profiles were changed significantly after cantharidin treatment,and 39 differential lipid metabolites were found.Additional analysis showed that these metabolites could mainly involve the metabolic pathways of triglyceride and acylcarnitine for cantharidin toxicity to LO2 cells.Conclusion:Cantharidin has obvious toxic effects on LO2 cells from the perspective of lipid metabolism.Moreover,the LO2 cytotoxicity induced by cantharidin is mainly related to the disorder of triglyceride and acylcarnitine metabolism.It can provide a scientific basis for cantharidin-induced hepatotoxicity.
基金supported by the National Natural Science Foundation of China(Grants no.82060754,81803838)The ability establishment of sustainable use for valuable Chinese medicine resources(2060302)+2 种基金Science and technology project of Guizhou health and Health Committee(gzwkj2021-441)Science and Technology Department of Honghuagang District of Zunyi city of Guizhou province of China([2020]-17)Zunyi Medical University Postgraduate Research Fund(ZYK187).
文摘Background:Cantharidin(CTD)is a commonly used natural product with anticancer properties;however,it has significant adverse effects,particularly hepatotoxicity.Glycyrrhetinic acid(GA),the active component of licorice,shows potential hepatoprotective effects.The protective effects and mechanism of GA against CTD-induced hepatotoxicity are still unclear.Objective:This study aims to elucidate the effect and mechanism of GA on CTD-induced hepatotoxicity in mice experiments.Methods:Construction of CTD-induced hepatotoxicity models and oral gavage GA intervention for 14 d.The liver index,ALT,AST and LDH levels in the serum of the mice were examined;HE staining was performed to observe pathological changes in the liver.The MDA level and SOD activities in liver tissue were tested.Western blot was conducted to determine Keap1/Nrf2 signaling pathway-related protein expression.Results:The results showed that GA significantly reduced the levels of ALT,AST,and LDH in the serum,which were increased by CTD.Additionally,it also exerted a substantial inhibitory effect on the reduction of SOD activity and the elevation of malondialdehyde content in liver tissue.Notably,the phenomena of nuclear swelling,necrosis,and inflammatory infiltration of liver tissue were significantly attenuated following oral administration of GA in mice.Subsequent research has demonstrated that GA effectively suppressed the CTD-triggered upregulation of Keap1 while increasing the CTD-induced downregulation of Nrf2,HO-1,and NQO1.Conclusion:These findings suggested that GA may protect against CTD-induced hepatotoxicity in mice by exerting antioxidative stress through the Keap1/Nrf2 signaling pathway.
文摘目的基于细胞药动学探究斑蝥素与黄芩苷配伍在亚细胞水平的分布规律,阐明其抗肝癌的增效机制。方法以人肝癌HepG2细胞为模型,采用超高效液相色谱-串联质谱(ultra-high performance liquid chromatography-tandem mass spectrometry,UPLC-MS/MS)定量分析单药(斑蝥素6μg/mL、黄芩苷30μg/mL)及配伍组(斑蝥素6μg/mL+黄芩苷30μg/mL)给药后12 h内,整体细胞及细胞核、线粒体、内质网和溶酶体各细胞器中药物浓度的动态变化,并应用Phoenix WinNonlin软件非房室模型计算药动学参数。结果在整体细胞水平,配伍使斑蝥素的胞内药时曲线下面积(area under the curve,AUC_(0~t))增加48.9%,清除率降低(P<0.05),但未显著影响黄芩苷的药动学行为。在亚细胞层面,配伍使斑蝥素与黄芩苷在细胞核、溶酶体、线粒体、内质网内的AUC_(0~t)分别增加了93.5%、46.4%、38.3%、52.3%和68.4%、40.0%、41.0%、46.7%(P<0.05、0.01)。此外,配伍后2种药物在线粒体内达峰时间(t_(max))提前,且斑蝥素在内质网中的平均驻留时间(mean residence time,MRT_(0~t))显著延长(P<0.01),表明两者配伍实现了时空协同的药物递送。结论斑蝥素/黄芩苷配伍可通过协同优化药物在细胞核、线粒体、内质网及溶酶体等关键亚细胞结构的分布,进而可能通过诱导DNA损伤、加速线粒体介导细胞凋亡及促进内质网应激等途径,增强抗肝癌效果,为基于细胞器靶向的中药配伍设计提供了理论依据。
基金National S&T Major Special Project on Major New Drug Innovation (2009ZX09301-003&2008ZX09103-390)
文摘Objective To increase the solubility and relieve the mucous irritation of cantharidin (CA) by preparing cantharidin-hydroxypropyl-β-cyclodextrin (CA/HP-β-CD) inclusion complex. Methods The inclusion complex was prepared by co-evaporation method and characterized by differential scanning calorimetry (DSC), X-ray diffractometry (XRD), and nuclear magnetic resonance (NMR). Results The disappearance of CA as well as the shift of exothermic peaks shown in DSC results indicated the complexation phenomenon. XRD results showed that the crystalline CA pattern had disappeared, and in NMR results, H-5 shifted from δ 3.731 to 3.695 after complexation and H-2 shifted from δ 3.626 to 3.598, which suggested that part of the drug had entered the HP-β-CD cavity to form an inclusion complex. The solubility increased 10.3 times after complexation and the mucous irritation of CA was relieved remarkably. Conclusion Through complexation with HP-β-CD, the solubility and dissolution rate of CA are improved significantly, and the irritation of musous is relieved.
文摘Transcatheter arterial embolization with hydroxycamptothecine, cantharidin and cisplatin,thoroughly mixed with large doses of interferon and interleukin-2, was performed in 48 cases with unre-sectable intermediate or advanced hepatocellular carcinoma. The results demonstrate a partial remissionrate of 54. 2%, significantly higher than that in embolization with chemotherapeutic agents alone (cis-platin, adriamycin and mitomycin, 32. 1%, P<O. 01) . Morever, the adverse reactions of hydroxycamp-tothecine and cantharidin, when applied systemically, including hematuria or urodynia were successfullyeliminated.
文摘目的探讨斑蝥素(Cantharidin)对结直肠癌SW480细胞增殖、侵袭及凋亡的影响,并初步阐明其潜在分子机制。方法采用体外培养的SW480细胞,通过MTS法和克隆形成实验检测细胞活力与长期增殖能力;利用Transwell实验评估细胞侵袭能力;运用流式细胞术分析细胞凋亡与周期分布;并采用Western Blot技术检测PI3K/AKT信号通路关键蛋白的表达及其磷酸化水平。结果与对照组相比,斑蝥素能够剂量依赖性地显著抑制SW480细胞的增殖(48 h IC_(50)为11.63μM)、克隆形成及侵袭能力。此外,斑蝥素可诱导细胞周期阻滞于G2/M期,并显著促进细胞凋亡。研究表明,斑蝥素处理能显著抑制PI3K与AKT的磷酸化,下调总PI3K、总AKT、CDK4、MMP9及抗凋亡蛋白Bcl-2的表达,同时上调促凋亡蛋白Bax的表达。结论斑蝥素可通过抑制PI3K/AKT信号通路,进而抑制结直肠癌SW480细胞的增殖与侵袭,并诱导其凋亡。
基金supported by the National Natural Science Foundation of China(grant number:31960117)the Miaozi Project in Science and Technology Innovation Program of Sichuan Province(grant number:2022006).
文摘Blister beetles(Coleoptera:Meloidae)produce a natural defensive toxin cantharidin(CTD),which has been used for various cancer treatments and other diseases.Currently,the lack of chromosome-level reference genomes in Meloidae limits further understanding of the mechanism of CTD biosynthesis and environmental adaptation.In this study,the chromosome-level genome assembly of Mylabris phalerata was generated based on PacBio and Hi-C sequencing.This reference genome was about 136.68 Mb in size with contig N50 of 9.17 Mb and composed of 12 chromosomes.In comparison to six other Coleoptera insects,M.phalerata exhibited multiple expanded gene families enriched in juvenile hormone(JH)biosynthetic process pathway,farnesol dehydrogenase activity,and cytochrome P450,which may be related to CTD biosynthesis.Consistently,the transcriptomic analysis suggested the“terpenoid backbone biosynthesis”pathway and“the juvenile hormone”as putative core pathways of CTD biosynthesis and presented eight up-regulated differential expression genes in male adults as candidate genes.It is possible that the restricted feeding niche and lifestyle of M.phalerata were the cause of the gene family’s contraction of odorant binding proteins.The ABC transporters(ABCs)related to exporting bound toxins out of the cell and the resistance to the self-secreted toxins(e.g.CTD)were also contracted,possibly due to other self-protection strategies in M.phalerata.A foundation of understanding CTD biosynthesis and environmental adaptation of blister beetles will be established by our reference genome and discoveries.
文摘目的评价叶酸修饰的斑蝥素/黄芩苷脂质体(DSPE-PEG2k-folate-cantharidin&baicalin@lipsomes,FA-Can&Bai@Lips)在正常大鼠与荷瘤大鼠体内的药动学及组织分布差异。方法以HepG2细胞悬液接种于大鼠右侧腋下诱导荷瘤大鼠模型,尾静脉注射FA-Can&Bai@Lips后采集不同给药时间点血浆与组织(心、肝、脾、肺、肾),采用超高效液相色谱-串联质谱联用技术(UPLC-MS/MS)测定血浆及组织中斑蝥素和黄芩苷浓度,应用Phoenix WinNonlin软件计算药动学参数,并分析比较FA-Can&Bai@Lips在正常机体状态与荷瘤状态下的药动学和组织分布差异。结果建立的同时测定斑蝥素与黄芩苷的UPLC-MS/MS方法线性关系良好,专属性、准确度与精密度、提取回收率与基质效应及稳定性等均符合生物样本检测要求。药动学参数表明,与正常组大鼠相比,荷瘤大鼠体内斑蝥素与黄芩苷的药时曲线下面积(area under the curve,AUC0-t、AUC0-∞)、平均驻留时间(mean residence time,MRT0-t、MRT0-∞)均显著升高(P<0.05),分别增加了55.68%、72.50%、43.10%、45.95%和15.10%、42.54%、9.09%、10.53%;斑蝥素在荷瘤大鼠体内半衰期(half-life,t1/2)缩短,但无显著性差异,而黄芩苷的t1/2显著延长(P<0.05),两者的表观分布容积(apparent volume of distribution,Vd)与清除率(clearance rate,CL)均明显降低。组织分布结果显示,斑蝥素与黄芩苷在荷瘤大鼠肝脏中浓度明显高于正常大鼠,其余组织药物浓度均显著低于正常大鼠。结论UPLC-MS/MS法分析速度快、简单、特异、灵敏,可用于大鼠血浆及组织中斑蝥素与黄芩苷的测定,且证实荷瘤状态会对FA-Can&Bai@Lips的体内药动学及组织分布产生明显影响。
文摘目的:制备叶酸修饰的共载斑蝥素和星形孢菌素的脂质体纳米递送体系(folic acid-modified liposomes nanodelivery system co-loaded with cantharidin and staurosporine,FA/CTD-STS/NL),并对其性质进行评价。方法:采用薄膜分散法制备FA/CTD-STS/NL,用凝胶柱-HPLC法测定脂质体的包封率。用透射电镜(transmission electron microscopy,TEM)观察脂质体的形态,激光粒度分析仪测定脂质体的粒径及其分布、Zeta电势,并考察其血清稳定性、长期稳定性和血液相容性。通过CCK-8法检测其细胞毒性。结果:FA/CTD-STS/NL外观呈类球形,分散均匀。平均粒径、多分散性指数、Zeta电势分别为(114.3±0.9)nm,(0.212±0.018)和-(1.19±0.13)mV,平均包封率分别为(89.62±0.67)%和(96.01±1.02)%。其血清稳定性和长期稳定性良好,溶血率均<5%,说明具有良好的血液相容性。FA/CTD-STS/NL对小鼠正常肝细胞(AML-12细胞)具有良好的细胞相容性。结论:本研究制备的FA/CTD-STS/NL具有良好的稳定性和生物安全性,包封率高,粒径符合抗癌纳米递送载体的要求,有利于药物在肿瘤组织的富集。本研究为后续FA/CTD-STS/NL体内外靶向性、抗肝癌作用及机制研究奠定实验基础。
