通讯机构:
[Xia, XH ] H;Hunan Univ Chinese Med, Sch Pharm, Changsha 410208, Hunan, Peoples R China.
摘要:
Ferroptosis represents a form of programmed cell death that is propelled by iron-dependent lipid peroxidation, thereby being distinguished by the prominent features of iron accumulation and lipid peroxidation. Ferroptosis has been implicated in numerous physiological and pathological phenomena, with mounting indications that it holds significant implications for cancer and other medical conditions. On one side, it demonstrates anti-cancer properties by triggering ferroptosis within malignant cells, and on the other hand, it damages normal cells causing other diseases. Therefore, in this paper, we propose to review the paradoxical regulation of ferroptosis in tumors and other diseases. First, we introduce the development history, concept and mechanism of ferroptosis. The second part focuses on the methods of inducing ferroptosis in tumors. The third section emphasizes the utilization of ferroptosis in different medical conditions and strategies to inhibit ferroptosis. The fourth part elucidates the key contradictions in the control of ferroptosis. Finally, potential research avenues in associated domains are suggested.
摘要:
Acne is a common chronic inflammatory disorder of the sebaceous gland in the hair follicle. Commonly used external medications cause skin irritation, and the transdermal capacity is weak, making it difficult to penetrate the cuticle skin barrier. Hair follicles can aid in the breakdown of this barrier. As nanomaterials progress, polymer-based nanocarriers are routinely used for hair follicle drug delivery to treat acne and other skin issues. Based on the physiological and anatomical characteristics of hair follicles, this paper discusses factors affecting hair follicle delivery by polymer nanocarriers, summarizes the common combination technology to improve the targeting of hair follicles by carriers, and finally reviews the most recent research progress of different polymer nanodrug-delivery systems for the treatment of acne by targeting hair follicles.
作者机构:
[Wu, Zixuan; Xia, Xinhua; Yang, J; Xia, XH; Yang, Jing] Hunan Univ Chinese Med, Sch Pharm, Changsha, Peoples R China.;[Gu, Zhenchang; Li, Xiaohuan] Guangzhou Univ Chinese Med, Affiliated Hosp 2, Guangzhou, Peoples R China.
通讯机构:
[Yang, J ; Xia, XH] H;Hunan Univ Chinese Med, Sch Pharm, Changsha, Peoples R China.
关键词:
BLCA;PyMGs;Immunity, m 6 A and immune checkpoint;Drug prediction;CNV;SNP
摘要:
Background Bladder cancer (BLCA) is a common urinary system malignancy with a significant morbidity and death rate worldwide. Non-muscle invasive BLCA accounts for over 75% of all BLCA cases. The imbalance of tumor metabolic pathways is associated with tumor formation and proliferation. Pyrimidine metabolism (PyM) is a complex enzyme network that incorporates nucleoside salvage, de novo nucleotide synthesis, and catalytic pyrimidine degradation. Metabolic reprogramming is linked to clinical prognosis in several types of cancer. However, the role of pyrimidine metabolism Genes (PyMGs) in the BLCA-fighting process remains poorly understood.Methods Predictive PyMGs were quantified in BLCA samples from the TCGA and GEO datasets. TCGA and GEO provided information on stemness indices (mRNAsi), gene mutations, CNV, TMB, and corresponding clinical features. The prediction model was built using Lasso regression. Co-expression analysis was conducted to investigate the relationship between gene expression and PyM.Results PyMGs were overexpressed in the high-risk sample in the absence of other clinical symptoms, demonstrating their predictive potential for BLCA outcome. Immunological and tumor-related pathways were identified in the high-risk group by GSWA. Immune function and m6a gene expression varied significantly between the risk groups. In BLCA patients, DSG1, C6orf15, SOST, SPRR2A, SERPINB7, MYBPH, and KRT1 may participate in the oncology process. Immunological function and m6a gene expression differed significantly between the two groups. The prognostic model, CNVs, single nucleotide polymorphism (SNP), and drug sensitivity all showed significant gene connections.Conclusions BLCA-associated PyMGs are available to provide guidance in the prognostic and immunological setting and give evidence for the formulation of PyM-related molecularly targeted treatments. PyMGs and their interactions with immune cells in BLCA may serve as therapeutic targets.
期刊:
Journal of Liposome Research,2023年33(3):283-299 ISSN:0898-2104
通讯作者:
Lili Zhou<&wdkj&>Xinhua Xia
作者机构:
[Xia, Xinhua; Xu, Yilin; Lin, Peng; Zhou, Lili; Zou, Manshu] Hunan Univ Chinese Med, Sch Pharm, Changsha, Peoples R China.;[Xia, Xinhua; Zhou, Lili] Hunan Univ Chinese Med, Sch Pharm, Changsha 410208, Peoples R China.
通讯机构:
[Lili Zhou; Xinhua Xia] S;School of Pharmacy, Hunan University of Chinese Medicine, Changsha, China<&wdkj&>School of Pharmacy, Hunan University of Chinese Medicine, Changsha, China
摘要:
In this study, cantharidin(CTD), a bioactive terpenoid in traditional Chinese medicine cantharidin, was selected as a model component to construct novel nano liposome delivery systems for hepatocellular carcinoma therapy. Previous studies have shown that although cantharidin has definite curative effects on primary liver cancer, it is associated with numerous toxic and side effects. Therefore, based on the glycyrrhetinic acid (GA) binding site and the asialoglycoprotein receptor (ASGPR) on the hepatocyte membrane, the surface of CTD liposomes was modified with stearyl alcohol galactoside (SA-Gal) or/and the newly synthesized 3-succinic-30-stearyl deoxyglycyrrhetinic acid (11-DGA-Suc) ligands, and the physicochemical properties, pharmacokinetics, invivo and invitro anti-liver tumor activity and its mechanism of modified liposomes were investigated. Compared to CTD-lip, SA-Gal-CTD-lip, and 11-DGA-Suc + SA-Gal-CTD-lip, 11-DGA-Suc-CTD-lip showed stronger cytotoxicity and increased inhibition of HepG2 cell migration had the highest apoptosis rate. The cell cycle results indicated that HepG2 cells was arrested mainly at G0/G1phase and G2/M phase. The results of invivo pharmacokinetic experiments revealed that the distribution of modified liposomes in the liver was significantly increased compared with that of unmodified liposome. In vivo tumor inhibition experiment showed that 11-DGA-Suc-CTD-lip had excellent tumor inhibition, and the tumor inhibition rates was 80.96%. The 11-DGA-Suc-CTD-lip group also displayed the strongest proliferation inhibition with the lowest proliferation index of 7% in PCNA assay and the highest apoptotic index of 49% in TUNEL assay. Taken together, our findings provide a promising solution for improving the targeting of nano liposomes and further demonstrates the encouraging potential of poor solubility and high toxicity drugs applicable to tumor therapy.
摘要:
Abstract: Cantharidin (CTD) is the major component of anticancer drugs obtained from Mylabris Cichorii and has a good inhibitory effect on several cancers, including hepatocellular carcinoma (HCC) and breast cancer. However, due to its toxicity, oral administration can cause various adverse reactions, limiting its clinical application. The aim of this work was to design glycyrrhetinic acid (GA)- and/or folate (FA)-modified solid lipid nanoparticles (SLNs) for the encapsulation of CTD to target HCC. Four CTD-loaded SLNs (cantharidin solid lipid nanoparticles (CSLNs), glycyrrhetinic acid-modified cantharidin solid lipid nanoparticles (GA-CSLNs), folate-modified cantharidin solid lipid nanoparticles (FA-CSLNs), and glycyrrhetinic acid and folate-modified cantharidin solid lipid nanoparticles (GA-FA-CSLNs)) were prepared by the emulsion ultrasonic dispersion method, and their physicochemical parameters were determined (particle size and distribution, morphology, zeta-potential, entrapment efficiency, drug loading, and hemolysis). Additionally, the antitumor activities of the four SLNs were evaluated comprehensively by tests for cytotoxicity, cell migration, cell cycle, apoptosis, cellular uptake, competition suppression assay, and in vivo tumor suppression assay. Four SLNs showed spherical shapes and mean diameters in the range of 75–110 nm with size dispersion (PDI) within the range of 0.19–0.50 and zeta-potential approximately –10 mV. The entrapment efficiency of CTD in SLNs was higher than 95% for all tested formulations, and no hemolysis was observed. Compared to GA-CSLNs or CSLNs, GA-FA-CSLNs and FA-CSLNs showed stronger cytotoxicity on hepatocellular carcinoma cells (HepG2), and the cytotoxicity of GA-FA-CSLNs on hepatocyte cells (L-02) was remarkably reduced compared with other formulations. GA-FA-CSLNs and FA-CSLNs also increased the inhibition of HepG2 cell migration, and FA-CSLNs had the highest apoptosis rate. The cell cycle results indicated that HepG2 cells were arrested mainly in the S phase and G2/M phase. Analysis of competition inhibition experiments showed that GA and FA ligands had targeted effects on HepG2 cells. The in vivo tumor inhibition experiment showed that GA-FA-CSLNs and FA-CSLNs had excellent tumor inhibition ability—their tumor inhibition rates were 96.46% and 89.92%, respectively. Our results indicate that GA-FA-CSLNs and FA-CSLNs have a promising future in the therapeutic intervention of HCC. Keywords: cantharidin; solid lipid nanoparticles; glycyrrhetinic acid; folate; antitumor; liver-targeting
作者机构:
[Li, Kun; Huang, Yuanyu; Lu, Mei] Beijing Inst Technol, Adv Res Inst Multidisciplinary Sci, Sch Life Sci, Inst Engn Med,Key Lab Mol Med & Biotherapy, Beijing 100081, Peoples R China.;[Xia, Xinhua; Huang, Yuanyu] Hunan Univ Chinese Med, Sch Pharm, Changsha 410208, Peoples R China.
通讯机构:
[Mei Lu; Yuanyu Huang] S;School of Life Science, Advanced Research Institute of Multidisciplinary Science, Institute of Engineering Medicine, Key Laboratory of Molecular Medicine and Biotherapy, Beijing Institute of Technology, Beijing 100081, China<&wdkj&>School of Life Science, Advanced Research Institute of Multidisciplinary Science, Institute of Engineering Medicine, Key Laboratory of Molecular Medicine and Biotherapy, Beijing Institute of Technology, Beijing 100081, China<&wdkj&>School of Pharmacy, Hunan University of Chinese Medicine, Changsha 410208, China
摘要:
As a new treatment technique, photothermal therapy (PTT) has aroused worldwide attention in cancer treatment, mainly due to its excellent absorption ability, easy regulation, and biodegradability. Photothermal conversion materials with enhanced permeability and retention effect can be targeted easily to tumor tissue. They can accumulate efficiently to tumor tissues and allow normal tissues and organs not to be affected by temperature, thus significantly helping to reduce the systemic toxicity and improve the antitumor effect. However, PTT alone often suffers from therapeutic resistance and reduced therapeutic efficacy, due to photothermal nanomaterial-mediated fundamental cellular defense mechanism of heat shock response, which could be inhibited by small interfering RNA (siRNA). Nevertheless, photothermal conversion materials as an excellent siRNA delivery carrier may considerably enhance the delivery efficiency of siRNA. Therefore, photothermal and RNA interfering (RNAi) synergistic therapy has recently aroused extensive attention in tumor treatment. In this review, we mainly summarize the recent advances of photothermal and RNAi synergistic therapy, including some synergistic therapeutic nanoplatforms of inorganic and organic photothermal materials and other combined therapies such as combining with small molecular antitumor agents or PDT/imaging. The combination of various treatment techniques may considerably improve the synergistic therapeutic effect of PTT and RNAi in the treatment of cancers.
摘要:
Cantharidin (CTD), a natural Chinese medicine constituent extracted from mylabris, is a potent drug against hepatocellular carcinoma. However, the clinical application of CTD was limited because of its toxicity and low solubility. In this work, a novel CTD-loaded liposome modified with 3-succinyl-30stearyl glycyrrhetinic acid (18-GA-Suc-CTD-Lip) was prepared to enhance liver-targeting efficiency and antitumor activity. 18-GA-Suc-CTD-Lip and CTD-Lip were successfully prepared by film dispersion method and totally characterized. The antitumor effects in vitro were evaluated by cell proliferation inhibition assay, transwell assay, cell cycle analysis, and an apoptosis test. Pharmacokinetic and biodistribution were all investigated to precisely reveal liver-targeting efficiency of 18- GA-Suc-CTD-Lip in vivo. The IC50 values of 18-GA-Suc-CTD-Lip in HepG2 (3.417 +/- 0.165 nmol/L) and Huh-7 (4.478 +/- 0.409 nmol/L) cells were much lower than that of CTD-Lip, indicating that antitumor effects of 18-GA-Suc-CTDLip were remarkable because of the modification of 18-GA-Suc. The maximum concentration in the liver of 18-GA-Suc-CTD-Lip (1.72 +/- 0.14 mg/g) was more than twice CTD-Lip (0.75 +/- 0.08 mg/g) at 30 min, illustrating that 18-GA-Suc-CTD-Lip possesses excellent liver-targeting efficiency. Conclusively, 18-GASuc-CTD-Lip could be a potential liver-targeting antitumor drug for hepatocellular carcinoma. (C) 2020 American Pharmacists Association (R). Published by Elsevier Inc. All rights reserved.
摘要:
The invention belongs to the field of targeted drug research and specifically relates to a glycyrrhetinic acid and/or folic acid ligand modified cantharidin solid lipid nanoparticle and a preparationmethod thereof. The product comprises a carrier and a ligand connected to the carrier, wherein the carrier is cantharidin solid lipid nanoparticles, and the ligand is 3-succinic acid-30-stearyl glycyrrhetinate and/or folate-polyethylene glycol-cephalin. The product is high in entrapment efficiency, large in drug loading capacity and capable of well exerting the drug effect.
期刊:
JOURNAL OF AOAC INTERNATIONAL,2019年102(5):1414-1422 ISSN:1060-3271
通讯作者:
Xinhua Xia
作者机构:
[Chen, Weishi; Zhou, Lili; Qiao, Yong; Xia, Xinhua] Hunan University of Chinese Medicine, School of Pharmacy, Changsha 410208, China;[Qi, Jianzhong; Fu, Guocheng] China Resources Pharmaceutical Group Limited, Chenzhou 423000, China
通讯机构:
[Xinhua Xia] H;Hunan University of Chinese Medicine , School of Pharmacy, Changsha 410208, China
摘要:
<jats:title>Abstract</jats:title>
<jats:p>Background: Ilex asprella (Hook. Et Arn.) Champ. Ex Benth. is one of the representative medicinal plants that naturally grows in South China. It serves as a major component of herbal tea as an aid for sore throat, toothache, and acne, and it is a folk medicine for treating upper respiratory tract inflammation resulting from fever, infectious hepatitis, and enteritis. Objective: To evaluate the quality of Ilex asprella, the bioactive components were identified comprehensively using quadruple time-of-flight (Q-TOF) MS, and the HPLC method for quality evaluation was established for the first time. Methods: Detection was conducted under the positive electrospray ionization mode with the 110 V fragment voltage and 4.0 kV capillary voltage for the ultra-performance LC–Q-TOF MS study. A Thermo Fisher C18 column (4.6 × 150 mm, 5 μm) associated with the 0.10% formic acid and acetonitrile as mobile phase and gradient elution was carried out for separation process, and the HPLC quality evaluation was detected at a wavelength of 340 nm. Results: The method was validated according to the International Conference on Harmonization regulation including LOQ, LOD, recovery, replication, precision, and linearity. The contents of five components were important for quality evaluation of Ilex asprella. Moreover, luteoloside and quercitrin had more significant impact than others. Conclusions: A specific accurate method has been proposed for the identification of the bioactive components and applied to simultaneous quantification analysis of five components in Ilex asprella. Highlights: The quality evaluation of Ilex asprella established based on its bioactive components can provide a solid promotion for applications of Ilex asprella in food and drug fields.</jats:p>
摘要:
BACKGROUND: Liver cancer is a common malignant tumor worldwide, and its morbidity and mortality increase each year. The disease has a short course and high mortality, making it a serious threat to human health. PURPOSE: The objective of this study was to create novel liver-targeting nanoliposomes to encapsulate cantharidin (CTD) as a potential treatment for hepatic carcinoma. METHODS: 3-Galactosidase-30-stearyl deoxyglycyrrhetinic acid (11-DGA-3-O-Gal)-modified liposomes (11-DGA-3-O-Gal-CTD-lip) for the liver-targeted delivery of CTD were prepared via the film-dispersion method and characterized. In vitro analyses of the effects on cellular cytotoxicity, cell migration, cell cycle, and cell apoptosis were carried out and an in vivo pharmacokinetics study and tissue distribution analysis were performed. RESULTS: Compared with unmodified liposomes (CTD-lip), 11-DGA-3-O-Gal-CTD-lip showed higher cytotoxicity and increased the inhibition of HepG2 cell migration, but they did not increase the apoptotic rate of cells. The inhibition mechanism of 11-DGA-3-O-Gal-CTD-lip on hepatocellular carcinoma was partly through cell cycle arrest at the S phase. Analysis of pharmacokinetic parameters indicated that 11-DGA-3-O-Gal-CTD-lip were eliminated more rapidly than CTD-lip. Regarding tissue distribution, the targeting efficiency of 11-DGA-3-O-Gal-CTD-lip to the liver was (41.15 +/- 3.28)%, relative targeting efficiency was (1.53 +/- 0.31)%, relative uptake rate was( 1.69 +/- 0.37)%, and peak concentration ratio was (2.68 +/- 0.12)%. CONCLUSION: 11-DGA-3-O-Gal-CTD-lip represent a promising nanocarrier for the liver-targeted delivery of antitumor drugs to treat hepatocellular carcinoma.