As is well-known, due to the complex pathogenesis of pancreatic cancer, monotherapy alone is no longer sufficient to meet current treatment goals. Combination drug therapy shows greater potential compared to monotherapy. Paclitaxel (PTX) and gemcitabine (GEM) are frequently used together to treat various types of cancers. However, the two drugs differ significantly in their physical and chemical properties, and simple coadministration can lead to severe toxic side effects. In this study, liposome technology was employed to coencapsulate paclitaxel palmitate (PTX-PA) and gemcitabine hydrochloride (GEM) to create paclitaxel palmitate and gemcitabine hydrochloride coloaded liposomes (PTX-PA/GEM-L), which were subsequently characterized. A series of in vivo and in vitro experiments were conducted to evaluate their stability, safety, and antipancreatic cancer activity. The particle size of PTX-PA/GEM-L was 99 +/- 1 nm (x +/- s, n = 3), with a PDI of 0.17 +/- 0.01 (x +/- s, n = 3) and a zeta potential of -33.37 +/- 0.15 mV. Notably, PTX-PA/GEM-L exhibited a sustained release profile in PBS, largely unaffected by pH changes. The cumulative release rate of GEM from PTX-PA/GEM-L after 48 h was between 57% and 60%. The formulation demonstrated good stability when stored in the dark at low temperatures. Additionally, it was found to be nonhemolytic and nonirritant to blood vessels, making it suitable for intravenous injection. Compared to the free GEM group, free PTX-PA group, and the physical mixture of GEM and PTX-PA, PTX-PA/GEM-L demonstrated an extended drug half-life, longer in vivo circulation time, better targeted accumulation at tumor sites, lower toxicity, and a more potent antitumor effect. This study demonstrates that the PTX-PA and GEM coloaded liposomal drug delivery system has superior in vivo antitumor efficacy compared to the simple combination of the two drugs, providing an effective combined treatment strategy for the clinical management of pancreatic cancer.
Chromobox protein homolog 2 (CBX2) exerts a multifaceted impact on the progression of aggressive cancers. The proteasome-dependent pathway is crucial for modulating CBX2 regulation, while the specific regulatory roles and mechanisms of deubiquitinating enzymes targeting CBX2 remain poorly understood. Mass spectrometry analysis identified ubiquitin-specific peptidase 27X (USP27X) as a deubiquitinating enzyme that targets CBX2. Overexpression of USP27X significantly enhances CBX2 levels by promoting deubiquitination, while deficiency of USP27X leads to CBX2 degradation, thereby inhibiting tumorigenesis. Furthermore, it has been revealed that glycogen synthase kinase 3 beta (GSK3β) can directly bind to and phosphorylate USP27X, thereby enhancing the interaction between USP27X and CBX2 and leading to further stabilization of the CBX2 protein. Clinically, the co-expression of high levels of USP27X and CBX2 in breast cancer tissues is indicative of a poor prognosis for patients with this disease. These findings collectively underscore the critical regulatory role played by USP27X in modulating CBX2, thereby establishing the GSK3β-USP27X-CBX2 axis as a pivotal driver of malignant progression in breast cancer.
以中药分析课程为切入点,从教师思政教育能力的提升、课程思政资料库的构建、课程专业内容与思政内容的有效融合、课程思政在中药分析相关行业的渗透实效等四个方面论述课程思政建设的改革思路与方法,充分发挥中药分析课程的育人功能.
通过对全国"双一流"高校实验室安全管理工作的调研,借鉴"双一流"高校经验,结合内蒙古医科大学药学院实验室安全管理的实例,提出健全实验室安全管理制度、规范实验室危险化学品存放、构建危险化学品细致化管理模式、重视实验室安全宣传教育的实验室安全管理工作建议,为国内西部医药类高校探索实验室安全管理工作提供思路和借鉴.
在新医科背景下,为了培养适应时代发展所需的高质量创新型应用型药学人才,本院以"整合药学"理念为指导,全面推进药学类专业本科生的创新创业教育,从教师队伍建设、科教协同育人、产教融合培养等方面开展了多层次的探索与实践,构建了医药院校药学类本科生创新创业能力培养的新模式.
目的 对苏格木勒-3挥发油自微乳(VOS-3-SMEDDS)的处方进行筛选及评价.方法 首先根据互溶结果初步筛选自微乳中各辅料,再通过伪三元相图对处方进行筛选,并对苏格木勒-3挥发油自微乳给药系统进行粒径、Zate电位以及稳定性考察.结果 制得的VOS-3-SMEDDS为淡黄色透明溶液,其最佳处方为苏格木勒-3挥发油(10%)、Tween 80(72%)、甘油(18%),其平均粒径为(19.7±0.25)nm,多分散指数为(0.191±0.01),Zate电位平均值为(-33.3±5.74)mV.通过稳定性考察得出VOS-3-SMEDDS在高速离心、长时间(6个月内)静置、不同稀释倍数(10、20、50、100、200倍)以及不同介质(蒸馏水、0.1 mol·L-1 HCl溶液、pH为6.8的PBS溶液)下均未出现分层.结论 本研究中VOS-3-SMEDDS制备工艺简单可行,得到的自微乳粒径小、稳定性良好,并且改善了苏格木勒-3挥发油的水溶性.
OBJECTIVE To establish the methods to identify the chemical components of Ixeris chinensis,and determine the contents of 7 components(chlorogenic acid,luteolin,quercetin,rutin,protocatechuic acid,isochlorogenic acid A,luteoloside).METHODS HPLC-Q-Exactive-MS was used to identify the chemical components of I.chinensis.The contents of 7 components in I.chinensis,including chlorogenic acid,were determined by HPLC-MS/MS.RESULTS A total of 45 components were identified in I.chinensis,including 20 organic acids,13 flavonoids,4 fatty acids,4 amino acids,3 nucleosides,and 1 coumarin.The linear range of chlorogenic acid,luteolin,quercetin,rutin,protocatechuic acid,isochlorogenic acid A and luteoloside were 503.00-25 150.00,42.00-2 100.00,5.05-252.50,20.05-1 002.50,25.10-1 255.00,750.00-37 500.00,196.00-9 800.00 ng/mL(r≥0.999 2),respectively.RSDs of precision,stability and reproducibility tests were all less than 3.00%(n=6),and average recovery ranged from 96.72%to 105.84%(all RSD<4.00%,n=6).The contents of 7 components in 3 batches of I.chinensis were 1 145.77-3 261.25,23.75-97.90,0.92-2.12,1.06-23.18,9.35-21.85,833.25-1 045.58,199.56-1 869.78 μg/g,respectively.CONCLUSIONS The established methods for identification and content determination are rapid and simple,and can be used for the identification of chemical components and the content determination of 7 components in I.chinensis.
ABSTRACT QingXiaoWuWei decoction (QXWWD) exerts a prominent therapeutic effect on the methicillin-resistant Staphylococcus aureus (MRSA)-induced pneumonia model in mice; however, its pharmacological mechanisms remain unclear. This study aimed to investigate the underlying pharmacological mechanisms of QXWWD in MRSA-induced pneumonia. In the present study, 62 compounds were identified using high-resolution mass spectrometry. Network analysis, leveraging mass spectrometry, pinpointed the infection-linked, immunity-associated, and inflammation-related pathways as predominant targets. QXWWD significantly alleviated MRSA-induced pneumonia in mice and decreased the levels of pro-inflammatory cytokines and chemokines. 16S ribosomal RNA (16S rRNA) sequencing revealed that QXWWD regulated gut microbiota composition in mice with MRSA-induced pneumonia, which correlated with the enrichment of certain short-chain fatty acids (SCFAs)-producing strains. Further analysis with targeted metabolomics confirmed that the acetic, propionic, and butyric acid levels in the mice’s serum were elevated significantly after QXWWD treatment. The fecal microbiota transplantation experiment suggested that gut microbiota from QXWWD-treated mice and SCFAs treatment may alleviate MRSA-induced pneumonia. Additionally, the untargeted metabolomic analysis further demonstrated that metabolic remodeling is significantly regulated by the QXWWD, particularly by the enhancement of the citrate cycle. In the case of QXWWD treatment, global transcriptome profiling revealed that genes, such as NLRP12 and CYP1A1, associated with macrophage antibacterial and immune activity, were downregulated. The results revealed that QXWWD regulated metabolic remodeling and macrophage gene expression network via the microbiota-SCFAs axis and thus alleviated MRSA-induced pneumonia in mice. IMPORTANCE Methicillin-resistant Staphylococcus aureus (MRSA) colonizes the upper respiratory airways and is resistant to antibiotics. MRSA is a frequently acquired infection in hospital and community settings, including cases of MRSA-induced pneumonia. Multidrug-resistant Staphylococcus aureus and the limited efficacy of antibiotics necessitate alternative strategies for preventing or treating the infection. QingXiaoWuWei decoction (QXWWD) protects against both gut microbiota dysbiosis and MRSA-induced pneumonia. Furthermore, the QXWWD-regulated metabolic remodeling and macrophage gene expression network contribute to its protective effects through the microbiota-short-chain fatty acid axis. The results of this study suggest that QXWWD and its pharmacodynamic compounds might have the potential to prevent and treat pulmonary infections, especially those caused by multidrug-resistant organisms. Our study provides a theoretical basis for the future treatment of pulmonary infectious diseases by manipulating gut microbiota and their metabolites via traditional Chinese medicine.
"三全育人,五育并举"是高校落实立德树人、开展育人工作的重要理念.内蒙古医科大学药学院在推进"三全育人"综合改革中,组建"全员育人"队伍,构建以专业能力培养为中心的"全程育人"模式及"全方位育人"体系,践行"五育并举",培养全面发展的高素质药学类人才.
目的 建立一种快速分析荜茇化学成分的方法,初步揭示荜茇的药效物质基础,为该药后续研究提供参考.方法 采用超高效液相色谱-四极杆/静电场轨道阱高分辨质谱(UPLC-Q-Exactive-MS)对荜茇提取物进行分析.色谱条件:色谱柱为Welch Ultimate C18(250 mm×4.6 mm,5 μm);流动相为甲醇(A)-0.1%甲酸水溶液(B),梯度洗脱(0~5 min,55%A,5~25 min,55%~90%A,25~50 min,90%~100%A);流速 1mL·min-1;检测波长272nm;柱温30℃;进样量20μL.质谱条件:离子源为HESI源;正、负离子模式同时检测;检测方式均为 Full-MS/dd-MS2;扫描范围 m/z 110~1000.使用 Compound Discoverer 3.0 软件对质谱数据进行初步筛查,获得化合物的保留时间、准分子离子峰的精确质量数及二级碎片等信息,再查阅相关数据库和文献与之比对分析,以此推断化合物结构.结果 根据保留时间和多级质谱碎片比对,初步鉴定出荜茇中的57个化学成分,包括16个A型酰胺类生物碱、13个B型酰胺类生物碱、9个C型酰胺类生物碱、10个D型酰胺类生物碱、3个E型酰胺类生物碱、6个O型化合物.结论 该方法有助于揭示荜茇的药效物质基础,可为进一步的药理学和活性机制研究提供参考.
利用多元线性回归可对待解决问题提出最优的回归方程组,说明各个自变量对因变量的影响;即使数据量很大,也不需要繁琐的运算过程,仍然能够迅速地得出结果,而且还能够通过系数得到对各变量的理解,因此该方法对中药研究中的有关问题特别适用.就多元线性回归联合紫外光谱(UV)法、红外光谱(IR)法和高效液相色谱(HPLC)法在中药生产加工、质量控制、药效物质基础研究等方面的应用进行综述,以期为多元线性回归法在中药研究中的更广泛应用提供参考.
目的 建立不同产地诃子中11种成分的含量测定方法,为其质量评价及优质种源的筛选提供参考.方法 以不同产地的16批诃子为检测样品,建立高效液相色谱串联三重四极杆质谱法测定诃子中牡荆素、没食子酸、没食子酸甲酯、没食子酸乙酯、鞣花酸、柯里拉京、莽草酸、阿魏酸、木犀草素、槲皮素、芦丁11种成分的含量.采用Shim-pack GIST-HP C18色谱柱,以0.1%甲酸溶液-甲醇为流动相进行梯度洗脱,流速为0.25 mL/min,进样量为3μL,柱温为35℃;采用电喷雾电离源,在正、负离子电离模式下进行检测,扫描方式为多反应监测模式,雾化气流量为3 L/min,加热气流量为10 L/min,接口温度为300℃,脱溶剂温度为526℃,加热块温度为400℃.运用灰色关联分析(GRA)和逼近理想解排序(TOPSIS)法对不同产地诃子进行比较分析和综合评价.结果 含量测定方法学考察结果符合相关要求.16批诃子样品中上述11种成分的含量分别为7.27~106.38、5370.24~31010.43、21.42~1097.50、4.26~111.09、17940.42~38490.18、6247.26~40182.18、12125.94~209519.96、2.71~9.04、0.24~44.12、1.49~9.17、25.35~126.51μg/g.GRA和TOPSIS分析结果均显示,样品H12(产地为云南)、H11(产地为广西)、H5(产地为湖南)、H14(产地为广东)、H13(产地为四川)、H8(产地为广东)、H1(产地为云南)的综合质量相对较好.结论 所建方法快速灵敏、准确可靠,可用于诃子的内在质量综合评价和优质种源筛选.
药物分析是内蒙古医科大学药学类专业的必修课程,药物分析实验是药物分析课程体系中重要的教学环节.为改善传统实验教学的局限性,提高教学质量,内蒙古医科大学药物分析教学团队以超星学习通和国家虚拟仿真实验中心为平台,搭建线上线下学习资源,创新实验教学方法,探讨线上线下混合式教学在药物分析实验课中的应用,提高了学生对药物分析实验课的兴趣,培养了学生的创新能力和实践能力.
近年来实验室安全事故时有发生,实验室危险废物属于实验室的重要危险源,高校药学类实验室危险废物产生量相对较大且种类繁杂,因此对其进行科学管理与处置是有效降低安全事故的重要手段.本文就目前高校药学类实验室危险废物普遍存在的问题,从如何减轻危险废物治理工作压力、提高管理水平、科学处置、加强应急演练、合理利用实验空间、保障贮存安全等方面有针对性地提出了相应的举措,从而为实验室安全保驾护航.
Sanzi San, a Mongolian medicine, comprises three herbs: Terminalia chebula, Melia toosendan, and Gardenia jasminoides. Clinically, Sanzi San is administered orally and distributed via blood to the action site, which implies that the absorption, distribution, metabolism, and excretion (ADME) are closely related to the pharmacological action and curative effect. Therefore, possible explanations for the material basis of Sanzi San were explored in this study preliminarily. A strategy based on serum pharmacochemistry was first applied to explore the absorbed bioactive components and metabolites of Sanzi San. Wistar rats were randomly divided into normal and dosing groups, which were provided with the Sanzi San's water extract for three days. Then, the rat's blood samples were obtained from their abdomiral aorta using a sterile blood collection tube after administering the medicine. The blood samples were then centrifuged at 3500 r/min for 10 min to obtain the serum samples. A practical method based on high performance liquid chromatography coupled with quadrupole and electrostatic field orbitrap high resolution mass spectrometry (HPLC-Q/Orbitrap HRMS) was developed to screen and analyze numerous bioactive components and metabolites adsorbed in the serum of the dosing rats after oral administration of the Sanzi San's water extract. Chromatographic separation was achieved on a SHIMADZU GIST C18 chromatographic column (150 mm×4.6 mm, 5 μm). The temperature of the column was maintained at 30 ℃. The flow rate was 0.5 mL/min, and the injection volume was 10 μL. The mobile phase comprised an aqueous solution of 0.1% formic acid and methanol under gradient elution. A heated electrospray ion (HESI) source was used with positive and negative ion scanning modes. To rapidly screen out and identify the absorbed bioactive components and metabolites of Sanzi San in the rat serum samples, a simple three-step approach was developed. First, the known components in Sanzi San were listed systematically by exploring various databases, such as the Web of Science, PubMed, and Chinese National Knowledge Infrastructure. In addition, relevant information on drug biotransformation and the characteristic fragmentation patterns of parent compounds were summarized. Second, the absorbed components and metabolites were ascertained using the Xcalibur 3.0 software. Based on the information related to the parent compound's structure, the software could be used to identify the unique peaks by comparing the chromatograms of the normal and dosing samples. Consequently, the total ion chromatograms of serum samples were established. Finally, the Compound Discover 3.0 software was used to predict the metabolic pathways and fragmentation of the absorbed compounds. Using this approach, 55 compounds were characterized, including 41 prototype components and 14 metabolites. The main prototype components in the serum sample were tannins, iridoids, and phenolic acids. The details of these compounds have been summarized and presented. Regarding the absorbed bioactive components and metabolites in the serum samples of rats administered with Sanzi San, phase Ⅰ and phase Ⅱ biochemical reactions were involved in the biotransformation pathways. The phase Ⅰ reaction modified the components and created sites for the phase Ⅱ reaction, involving reduction and hydrolysis. The phase Ⅱ reaction coupled groups to existing conjugation sites, including glucuronide to glucuronic acid, sulfate, and methyl. MS/MS spectra indicated that methylation, demethylation, and dehydroxylation are the metabolic pathways of procyanidins. Additionally, glucuronidation, deglucosidation, hydration, and demethylation are the metabolic pathways of iridoids in Sanzi San. This study comprehensively analyzed the components of the Sanzi San's water extract absorbed in the rat's serum. Our results revealed information regarding the pharmacodynamic substances and the major pathways involved in the ADME of Sanzi San. Further, potential medicinal ingredients for the pharmacological effects and clinical use of Sanzi San were explored at the serum pharmacochemistry level.
Objective:To explore the therapeutic mechanism of Mongolian medicine Sendeng-4 decoction for rheumatoid arthritis by 99Tc m-hydrazinonicotinamide-(polyethylene glycol) 4-E[(polyethylene glycol) 4-c((Arg-Gly-Asp)fk)] 2 (3PRGD 2) imaging. Methods:A total of 200 female SD rats (age: 6-7 weeks) were divided into collagen-induced arthritis (CIA) group ( n=176) and blank control group ( n=24). Rats in the CIA group were divided into Sendeng-4 decoction treatment group ( n=24), etanercept treatment group ( n=24), and negative control group ( n=24) by simple random sampling method. 99Tc m-3PRGD 2 SPECT/CT imaging was performed before and after modeling and treatment. The differences of target/non-target (T/NT) ratio and serological, pathological, and immunohistochemical results among groups were compared by one-way analysis of variance or Kruskal-Wallis rank sum test. The correlation was analyzed by Pearson correlation or Spearman correlation analysis. Results:There were 95 (95/176) CIA models successfully established. The T/NT ratios of Sendeng-4 decoction treatment group and etanercept treatment group were lower than that of negative control group (0.260± 0.094, 0.238±0.099, 0.766±0.144 ; F=163.00, P<0.001), while there was no significant difference between the two drug treatment groups ( P>0.05). After drug treatment, serum levels of vascular endothelial growth factor (VEGF), tumor necrosis factor-α (TNF-α) and α vβ 3 were significantly lower than those of negative control group ( F values: 49.43-92.36, all P<0.001), pathological score was also lower than that of negative control group ( H=34.25, P<0.001), and levels of immunohistochemical makers (VEGF, TNF-α, α vβ 3, CD31, CD34) were also lower than those of negative control group ( H values: 13.51-26.84, all P<0.001), while there were no significant differences between the two drug treatment groups (all P>0.05). The T/NT ratios were positively correlated with above indictors in Sendeng-4 decoction treatment group ( r values: 0.56-0.59, rs values: 0.49-0.69), etanercept treatment group ( r values: 0.50-0.55, rs values: 0.46-0.70) and negative control group ( r values: 0.55-0.80, rs values: 0.58-0.86, P<0.001 or P<0.05). Conclusion:Verified by 99Tc m-3PRGD 2 SPECT/CT imaging and molecular pathology, Mongolian medicine Sendeng-4 decoction can inhibit neovascularization by down-regulating vascular factors such as VEGF, resulting in delaying the progression of the disease and improving clinical symptoms.
目的 建立蒙药三子散高效液相色谱(HPLC)指纹图谱,通过化学模式识别方法综合评价其内在质量.方法 采用HPLC法,以京尼平苷色谱峰为参照峰,采用《中药色谱指纹图谱相似度评价系统(2012版)》绘制15批三子散的HPLC指纹图谱并进行相似度评价,标定并指认共有峰.结合聚类分析、主成分分析和正交偏最小二乘法-判别分析对15批三子散的指纹图谱进行质量评价,筛选影响其质量的差异性标志物.结果 15批三子散中共有29个共有峰,相似度均不低于0.952,表明15批三子散的化学组成一致性较好;共指认了诃子次酸、没食子酸、石榴皮鞣素、安石榴苷A、安石榴苷B、jasminoside B、咖啡酸、柯里拉京、京尼平苷、诃子鞣酸、1,2,3,4,6-O-没食子酰葡萄糖、诃子林鞣酸、鞣花酸13个共有峰.聚类分析与主成分分析均可将15批三子散分为4类,且分类结果一致,表明15批三子散的质量存在一定差异;结合正交偏最小二乘法-判别分析筛选出导致批次间质量差异的14个差异性标志物(诃子次酸、没食子酸、鞣花酸等).结论 建立的HPLC指纹图谱分析方法简便、稳定,结合化学模式识别分析可用于三子散的质量控制.
目的:在鉴别三臣丸原型入血成分的基础上,结合A549细胞血清药理实验,利用灰色关联度软件分析评价三臣丸入血成分中可能的药效成分.方法:大鼠给药后采集5个不同时间点的血浆,采用HPLC-MS/MS定性分析血浆中部分三臣丸成分,以A549细胞的存活率及细胞内ROS的含量评价三臣丸含药血清的药理功效,灰色关联度软件进行综合性分析.结果:大鼠含药血浆中共鉴定了30种原型入血成分,含药血清进行了血清药理实验;含药血清具有抑制A549细胞增殖及参与A549细胞凋亡的药理作用,并具有量效关系;其中胆酸、猪去氧胆酸、山柰酚、山柰酚-3-O-芸香糖苷、红花黄色素A、甘西鼠尾草酸A和牛磺胆酸与A549细胞的药理作用相关性较强.结论:胆酸、猪去氧胆酸、山柰酚、山柰酚-3-O-芸香糖苷、红花黄色素A、甘西鼠尾草酸A和牛磺胆酸可能是三臣丸含药血浆中的药效成分,该研究为三臣丸的药效物质基础研究提供了新的依据.
中药质量控制和质量标准的建立是制约中医药现代化和国际化发展的关键因素.化学计量学在中药分析中的运用为复杂的中药系统提供了一个有别于传统中药研究的新思路,而质量标志物概念的提出则为规范中药质量研究和标准建立奠定了基础.本文就化学计量学方法在中药质量标志物研究中的应用展开综述,对化学计量学在中药相关因素(产地、品种、炮制和制备工艺)中差异性质量标志物的辨识,化学计量学综合系统生物学(代谢组学、网络药理学等)以及新兴学术思想(谱毒相关、中医方证代谢组学)筛选质量标志物的方面进行了简单的梳理总结,以期为中药质量标志物的进一步研究和质量控制方面的创新提供理论基础.
基于内蒙古医科大学的药物分析的教学现状,文章主要从微课及相关教学资源的建设、教学流程的重构、以过程为中心的评价三方面,阐明混合式金课模式与药物分析传统教学的融合过程.将以成果为本的新型教学理念应用到实际教学过程中,为药物分析课程教学改革提供借鉴.