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2023 Vol. 41, No. 3

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Progress in preparation and application of biomimetic nano carriers for cell membrane
DAI Yu, WANG Hongbo, BIAN Kangqing, GUO Lingyi, YU Yuan
2023, 41(3): 135-138, 145. doi: 10.12206/j.issn.2097-2024.202202058
Abstract(7487) HTML (13791) PDF (1276KB)(244)
Abstract:
Nanocarriers prepared from organic or inorganic materials are widely used in drug targeting system and diagnosis and treatment of disease. However, there are some problems, such as poor targeting, short circulation time in vivo and improvement in the biocompatibility. Biomimetic nanocarriers has carried out research on the issues, which based on different kinds of cell membrane for the nanocarriers modification, endogenous biofilm improving the biocompatibility of carriers in vivo, more accurate targeting, and even producing immunotherapeutic effect. The principle, method, targeting mechanism and therapeutic effect of biomimetic nano carrier technology of cell membrane have been reviewed in this paper, which provide a new direction for the research of new drug delivery system.
Application of metabonomics in breast cancer
MA Xiaoyu, LUO Caiping, LIU Yue
2023, 41(3): 139-145. doi: 10.12206/j.issn.2097-2024.202109112
Abstract(8199) HTML (2104) PDF (1032KB)(55)
Abstract:
Breast cancer is a kind of malignant tumor discovered lately, with a high incidence and a poor prognosis. The shortage of relevant biological biomarkers lead to the unsatisfactory treatment efficacy and the early diagnosis in breast cancer. Metabolomics is a new discipline that uses high-throughput analysis techniques to study the dynamic changes of endogenous metabolites under the influence of different pathological physiological stimulation or gene mutations, which has provided a novel way for biomarker screening and disease diagnosis and treatment. The overview of metabolomics and its applications in breast cancer early diagnosis, drug efficacy evaluation, and disease prognosis were summarized in this review.
Research progress of cryptotanshinone on anti-fibrosis and its mechanism
LIU Yayi, ZHANG Junping
2023, 41(3): 146-148, 186. doi: 10.12206/j.issn.2097-2024.202208061
Abstract(4675) HTML (2573) PDF (1206KB)(16)
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As a natural compound with high efficiency and low toxicity, cryptotanshinone (CTS) has a good anti-fibrosis effect in various organs and tissues. However, its mechanism of action has not been clearly defined, and there is no systematic literature review to describe its potential anti-fibrosis mechanism. The efficacy and mechanism of cryptotanshinone in the treatment of fibrosis in various organs were summarized and the use prospects were put forward in this paper.
Evaluation of toxin-induced injury and protective effect of triptolide based on a cardiovascular chip model
HE Xiaoli, SHI Yiwei, CHEN Lan, LIU Yue, HONG Zhanying
2023, 41(3): 149-154, 159. doi: 10.12206/j.issn.2097-2024.202206018
Abstract(3100) HTML (1145) PDF (3717KB)(19)
Abstract:
  Objective  To construct a cardiovascular chip model for evaluating the damage of vascular glycocalyx induced by four marine toxins: okadaic acid (OA), conotoxin (CTX), tetrodotoxin (TTX) and gymnodimine (GYM), and explore the protective effect of triptolide on toxin-induced injury.   Methods  Human umbilical vein endothelial cells(HUVEC) were inoculated into a three-channel microfluidic chip. CCK-8 method and immunofluorescence staining were used to analyze the damage of cell viability and glycocalyx tissue induced by low, middle and high concentrations of marine toxin, as well as the protective effect of triptolide on toxin-induced injury.   Results  The cells in the cardiovascular chip grew well and had structurally intact glycocalyx. Compared with the control group, the activity of HUVEC cells were inhibited in group of the medium and high concentration of OA and high concentration of GYM (P<0.05). The activity of cells had not been inhibited by CTX and TTX significantly , but all the four toxins caused serious damage to the glycocalyx tissue (P<0.01). After pre-protection with triptolide, the toxicity of the four toxins to HUVEC cells and the damage rate of glycocalyx decreased significantly.   Conclusion  The four marine biotoxins could damage the activity and glycocalyx of HUVEC cells in a dose-dependent manner, while triptolide has a protective effect on HUVEC cells injured by toxin.
Effect and mechanism of Bajitianwan on preventing D-galactose-induced osteoblast bone loss
XU Weifan, XU Wumu, DING Luying, JIANG Yiping, XIA Tianshuang, XIN Hailiang
2023, 41(3): 155-159. doi: 10.12206/j.issn.2097-2024.202202030
Abstract(3263) HTML (1438) PDF (1645KB)(19)
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  Objective  To explore the effect and mechanism of Bajitianwan on preventing D-galactose (D-gal)-induced osteoblast bone loss.   Methods  Osteoblasts isolated from 24 h old Wistar rats were injured by D-gal and intervened with Bajitianwan extract. The osteoblastic proliferation and differentiation were determined by MTT and alkaline phosphatase (ALP), respectively. The cell reactive oxygen species (ROS) levels were detected by DCFH-DA fluorescent probes. The expression of cellular oxidation-related protein nuclear factor erythroid 2-related factor 2 (Nrf2), phosphorylated protein kinase B (p-AKT), protein kinase B (AKT), heme oxygenase-1 (HO-1), and NADPH quinone oxidoreductase 1 (NQO1) were detected by Western blotting. The intranuclear expression of Nrf2 protein was measured by immunofluorescence.   Results  Bajitianwan extract had significantly increased the osteoblastic proliferation and differentiation, and significantly reduced the intracellular ROS level. Bajitianwan extract had activated the PI3K/AKT pathway via activating the phosphorylation of AKT in osteoblasts, and promoted NQO1 and HO-1 expression. In addition, Bajitianwan had significantly promoted the expression of Nrf2 in the nucleus of osteoblasts, activating Nrf2 signaling pathway, and further promoted bone formation.   Conclusion  This study confirmed that Bajitianwan could prevent D-gal injured osteoblastic bone loss for the first time. The mechanism might be related to the regulation of oxidative stress associated PI3K/AKT and Nrf2 signaling pathway.
Anti-tumor mechanism study on saffron by network pharmacology and reverse molecular docking
MENG Xiangqing, LI Lihua, WANG Hongrui, JIA Dan, JIA Min
2023, 41(3): 160-167, 196. doi: 10.12206/j.issn.2097-2024.202206066
Abstract(5488) HTML (2225) PDF (7355KB)(46)
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  Objective  To explore the anti-tumor mechanism of saffron (Crocus sativus L.) by network pharmacology and reverse molecular docking techniques.   Methods   The main chemical components of saffron were obtained by searching published literature and TCMSP database. The potential targets of these components were predicted using PharmMapper server. The corresponding target genes were identified from UniProt database. The underlying anti-tumor targets of saffron were obtained by mapping the disease genes of cancer or tumor with GeneCards, OMIM and TTD databases. Cytoscape software was used to construct the action target network of saffron active components. The protein-protein interaction analysis was performed by String database, and the GO function and KEGG pathway enrichment analysis were performed by Metascape platform. Finally, molecular docking was performed to evaluate the binding of main components with their potential targets.   Results   A total of 9 active ingredients in saffron including quercetin, kaempferol, isorhamnetin, picrocrocin and crocin I, were identified, which might act on 37 key targets including AKT1, CCND1, MMP9, EGFR, TP53, involved in P53, TNF and other signaling pathways. Molecular docking indicated modest binding potency through hydrogen bonding, and hydrophobic interactions.   Conclusion  The anti-tumor effect of saffron was evaluated via the network of components-targets-pathways, which might provide a foundation for further research.
Pharmacokinetic study of HMS-01 in mice
SHI Xiaofei, CHEN Yi, XIANG Kefa, JING Kai, GAO Yue, LIU Xia
2023, 41(3): 168-172, 191. doi: 10.12206/j.issn.2097-2024.202211015
Abstract(4072) HTML (1565) PDF (1525KB)(49)
Abstract:
  Objective  To study the pharmacokinetics of HMS-01 in mice and provide support for subsequent studies.   Methods  Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to establish a sensitive and specific method for the determination of the concentration of HMS-01 in plasma and other biological samples. The pharmacokinetics of HMS-01 in C57BL/6J mice were studied by the established method. To obtain the basic pharmacokinetic parameters, three doses of HMS-01 were given orally and one dose of HMS-01 was given intravenously.   Results  The pharmacokinetic results of mice showed that the intestinal absorption of HMS-01 was fast, the oral bioavailability of HMS-01 in mice was moderate (50% to 70%). The exposure levels (AUC and cmax) of HMS-01 in mice increased with the increase of dosage, while the AUC was linearly correlated with the increase of dosage. After intravenous administration of HMS-01, the half-life period in mice was about 1 h which was not long. The plasma clearance rate (CLtotal.p) was 2.8 L/h·kg, which was similar to the hepatic blood flow of mice. The apparent volume of distribution (VSS) was 5 L/kg, which was much larger than the total mouse fluid. There were significant differences in AUC and F (P<0.05), but no significant differences in parameters such as cmax,AUC0−∞,t1/2,CLtot,p,MRT,Vss in male and female mice which were given 30 and 60mg/kg HWS-01 orally.   Conclusion  The pharmacokinetic process of HMS-01 in mice showed gender differences, and the area under the curve of blood concentration time and bioavailability of female mice were higher than that of male mice. As oral bioavailability was reasonable, further in vivo studies on HMS-01 in mice with heart failure by oral administration could be considered to provide evidence.
Textual research on the name and reality of edible and medicinal Zisu
LI Chunyan, XU Chen, LU Pengfei, HUANG Baokang
2023, 41(3): 173-176. doi: 10.12206/j.issn.2097-2024.202112055
Abstract(6208) HTML (1991) PDF (1263KB)(27)
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  Objective  To make a textual research on Zisu about the name, origin, morphology and efficacy, a dual-purpose medicinal and edible plant, in order to make the original clear and provide reference basis for clinical application.   Methods  Textual research was carried out from the aspects of synonym, distribution, morphology, efficacy, toxicity and side effects of the plants.   Results  Zisu, Baisu and Su in the herbal medicine of past dynasties belong to the Ren category, which are species or varieties of Perilla frutescens(L.)Britt. Zisu has purple leaves, and its stems, leaves and seeds are used as medicine to mainly lower Qi. While Baisu has green leaves, which could cure wind cold.   Conclusion   There are significant differences in botanical morphology and pharmacological efficacy between Zisu and Baisu, which should be distinguished and used separately. Zisu is a dual-purpose traditional Chinese medicine with a long application history. Baisu is not suitable for edible consumption.
The eye irritation test and pharmacokinetic study of tacrolimus-loaded cationic nanoemulsion-based in-situ gel in rabbits
LIN Xin, ZHANG Jialiang, ZHOU Xin, SONG Hongtao
2023, 41(3): 177-181. doi: 10.12206/j.issn.2097-2024.202104055
Abstract(4038) HTML (1725) PDF (1158KB)(15)
Abstract:
  Objective  To study the eye irritation and the pharmacokinetics of tacrolimus-loaded cationic nanoemulsion-based in-situ gel in rabbits.   Methods  The eye irritation of tacrolimus-loaded cationic nanoemulsion-based in-situ gel in rabbits was observed by histological cross-sections of external ocular tissues stained with HE. The aqueous humor of rabbit eyes was extracted by corneal puncture and analyzed by HPLC-MS for pharmacokinetic study.   Results  Tacrolimus-loaded cationic nanoemulsion-based in-situ gel had no significant irritation on rabbit eyes. The pharmacokinetic parameter showed that the AUC of tacrolimus-loaded cationic nanoemulsion-based in-situ gel was (128.34±13.09) ng·h/ml, which was 1.13 times of tacrolimus-loaded cationic nanoemulsion (113.61±12.36) ng·h/ml and 1.88 times of Talymus® (68.25±10.82) ng·h /ml.   Conclusion  Tacrolimus-loaded cationic nanoemulsion-based in-situ gel had the advantages of low irritation, long retention time and high bioavailability in rabbit eyes. It has a good potential for clinical application.
Establishment of determination of tetrodotoxin sustained-release microspheres
WANG Qi, LU Guangzhao, LI Yuan, FAN Li, ZHANG He, LU Ying
2023, 41(3): 182-186. doi: 10.12206/j.issn.2097-2024.202208060
Abstract(4076) HTML (1467) PDF (1282KB)(11)
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  Objective  To establish a detection method for the determination of tetrodotoxin (TTX) in sustained-release microspheres.   Methods  The HPLC separation of tetrodotoxin was performed on an Agilent ZORBAX SB-C18 column (4.6mm×150mm,5 μm) with acetonitrile, 8mmol/L sodium heptane sulfonate containing 0.005% TFA (5:95) (pH 4.0) as the mobile phase. The flow rate was 1.0 ml/min. The UV detection wavelength was 200 nm and the column temperature was 30 °C.   Results  The method had good specificity and linearity of TTX in the concentration range of 1−20 μg/ml. The intra-day precision, inter-day precision, stability and repeatability of the method were good, and the average recoveries were found between 98.0% and 102.0%.   Conclusion  This study established an HPLC method which was suitable for the determination of tetrodotoxin sustained-release microspheres. The method is accurate and reliable within the applicable range, with strong specificity, which could lead to quantitative detection.
Research on historical evolution of Combretum indicum
WANG Xiujuan, FENG Hao, JIANG Songfan, JIANG Shenggui, GU Tianlei, SUN Lianna
2023, 41(3): 187-191. doi: 10.12206/j.issn.2097-2024.202211075
Abstract(4431) HTML (1807) PDF (1002KB)(8)
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Combretum indicum can kill insects and benefit the spleen and stomach, which is the most important medicine to treat children's diseases. The classics of materia medica, calendar edition of Chinese Pharmacopoeia, local processing standards and related literature were reviewed to sort out the processing history of Combretum indicum, compare the ancient medicinal parts and processing methods, and summarize the inclusion in national and local standards. The history of the evolution of Combretum indicum was summarized in order to provide ideas for rational drug use in clinical and standard improvement.
Monitoring of residual cisatracurium besylate in elderly patients plasma at post operation by UPLC-MS/MS
XU Jiaming, ZHOU Xiaofang, GUO Jianrong
2023, 41(3): 192-196. doi: 10.12206/j.issn.2097-2024.202206023
Abstract(2437) HTML (1155) PDF (1030KB)(5)
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  Objective  To establish a method for the determination of cisatracurium besylate in human plasma by UPLC-MS/MS which could be used in the monitoring of drug residual in plasma of elderly patients after operation.   Methods  The samples were precipitated with 0.1% formic acid-acetonitrile solution and separated by an SHISEIDO ADME column(3.0 mm×100 mm, 2.7 μm) for isocratic elution with the mobile phase of water containing 0.1% formic acid with 2 mmol/L ammonium acetate and acetonitrile (30 : 70, V/V). MS condition was optimized in the positive ion detection mode by multiple reaction monitoring (MRM), along with the Agilent jet stream electrospray source interface (AJS-ESI). The precursors to the product ion transitions were m/z 464.3→358.2 for cisatracurium besylate and m/z 557.4→356.3 for vecuronium bromide (the internal standard, IS). Plasma samples of elderly patients undergoing spinal surgery were collected after anesthesia induction, at the end of surgery, 0.5 h and 1 h after surgery, and from the blood bags while autologous blood transfusion, and stored in cryopreservation tubes with 2% formic acid solution. Then the contents of cisatracurium besylate were determined. The effects of autogenous blood transfusion on plasma concentration of cisatracurium besylate in elderly patients after surgery evaluated.   Results  The calibration curve was linear in the range of 20-5 000 ng/ml for cisatracurium besylate in human plasma, r=0.999 7. The intra-day and inter-day precision and accuracy were good (RSD<10%, RE<±10%). The matrix effect of different concentrations was 71.88%~80.64%. The recovery of different concentrations was 83.62%~88.87%. The recovery of vecuronium bromide (IS) was 125.91%, which conformed with the requirement of methodological validation. There was a certain degree of residual cisatracurium besylate in the plasma of elderly patients, so the extubation time should be strictly controlled and the stay time of patients in the anesthesia recovery room should be appropriately extended.   Conclusion  The method is sensitive, accurate, and efficient, which could be used for the determination of cisatracurium besylate in human plasma of elderly patients after operation.