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.
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.
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.
摘要：
Small interfering RNA (siRNA) enables efficient target gene silencing by employing a RNA interference (RNAi) mechanism, which can compromise gene expression and regulate gene activity by cleaving mRNA or repressing its translation. Twenty years after the discovery of RNAi in 1998, ONPATTRO™ (patisiran) (Alnylam Pharmaceuticals, Inc.), a lipid formulated siRNA modality, was approved for the first time by United States Food and Drug Administration and the European Commission in 2018. With this milestone achievement, siRNA therapeutics will soar in the coming years. Here, we review the discovery and the mechanisms of RNAi, briefly describe the delivery technologies of siRNA, and summarize recent clinical advances of siRNA therapeutics.
期刊：
Journal of AOAC International,2019年102(5):1414-1422 ISSN：1060-3271
通讯作者：
Xia, Xinhua
作者机构：
[Xia, Xinhua; Chen, Weishi; Zhou, Lili; Qiao, Yong] Hunan Univ Chinese Med, Sch Pharm, Changsha 410208, Hunan, Peoples R China.;[Qi, Jianzhong; Fu, Guocheng] China Resources Pharmaceut Grp Ltd, Chenzhou 423000, Peoples R China.
通讯机构：
[Xia, Xinhua] H;Hunan Univ Chinese Med, Sch Pharm, Changsha 410208, Hunan, Peoples R China.
摘要：
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 x 150 mm, 5 mum) 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.
