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  • Yi-chi SHEN, Xue-lian FAN, Fei WANG, Gang CHEN
    Acta Pharmaceutica Sinica. 2021, 56(9): 2485-2494.

    Dendritic cells (DCs) are the most powerful and professional antigen-presenting cells (APCs) known at present. They play vital roles in the initiation and regulation of immune responses in body. Therefore, DC-based vaccine delivery system has gradually become a hotspot of basic scientific research and clinical treatment. DCs can be loaded with whole-cell antigens, nucleic acids, peptides, proteins (such as neoantigens) and nanoparticles to induce specific cellular immune responses and humoral immune responses after antigen processing, presentation and targeting delivery in vivo for the prevention and treatment of various diseases including cancers and microorganism infections. Vaccine-based on this technique is called dendritic cell (DC) vaccines. Great process in DC vaccines has been achieved in recent years. Therefore, we reviewed the characteristics of DC, types of DC vaccines and their clinical research progress in this paper.

  • Hui WANG, Ying CAI, Min LIU, Zhan-ying HONG, Yi-feng CHAI
    Acta Pharmaceutica Sinica. 2021, 56(9): 2394-2402.

    The paper aims to compare the protective effect of Salvia miltiorrhiza and Anemarrhena asphodeloides on AD cell model and investigate its protective mechanism by cell metabolomics platform. AD cell model was established by the abnormal phosphorylation of Tau protein in SH-SY5Y cells induced by okadaic acid. The protective effect of the extract of Salvia miltiorrhiza and Anemarrhena asphodeloides on the model was evaluated by cell proliferation-toxicity experiment. The metabolomics platform was used to study the efficacy of Salvia miltiorrhiza and Anemarrhena asphodeloides comprehensively, explore the potential biomarkers related to AD and the effect of drugs on the potential biomarkers. Salvia miltiorrhiza extract had a certain protective effect on the AD model (P < 0.05), while the Anemarrhena asphodeloides extract had no significant protective effect (P > 0.05). 45 significant differential metabolites and the related 12 metabolic pathways were identified using UHPLC-QTOF/MS platform, which were related to the AD cell model. After administration of Salvia miltiorrhiza extract, 30 different metabolites appeared callback, while after intervention of Anemarrhena asphodeloides extract, 7 metabolites appeared callback. The results showed that the extracts of Salvia miltiorrhiza and Anemarrhena asphodeloides had certain protective effects on the AD cell model with Tau protein abnormal phosphorylation, but Salvia miltiorrhiza had more extensive targets and could significantly improve the cell viability. The mechanism may be related to the regulation of the metabolic pathways of AD cell model induced by okadaic acid.

  • Li-ping ZHAO, Dan-qing SONG, Yan-xiang WANG
    Acta Pharmaceutica Sinica. 2021, 56(9): 2472-2484.

    As a pleiotropic cytokine, interleukin-6 (IL-6) participates in many physiological activities in vivo. IL-6 plays an important role in the physiology and pathology of chronic inflammation, autoimmune diseases, tumors and other diseases through diverse mechanisms. At present, inhibitors targeting IL-6/IL-6R have been shown to improve treatments for some inflammatory diseases such as rheumatoid arthritis and systemic juvenile idiopathic arthritis. IL-6 binds to a specific receptor to activate the downstream JAK/STAT3 signaling pathway. However abnormally activated STAT3 often appears in various types of malignant tumors and participates in the occurrence and development of tumors. In addition, studies have shown that IL-6 is a key factor in the cytokine storm associated with COVID-19 patients. The physiological participation of IL-6/STAT3 pathway in complex diseases makes this pathway become a research hotspot for drug discovery. Therefore, we summarize the latest research progress of small molecular inhibitors on IL-6/STAT3 signaling pathway, in order to provide a reference for the development of IL-6/STAT3 related drug in the future.

  • Jia-jun CHEN, Xue-mei QIN, Guan-hua DU, Yu-zhi ZHOU
    Acta Pharmaceutica Sinica. 2021, 56(9): 2464-2471.

    Depression was a complex and difficult to regulate disease, which was closely related to purinergic system and purine metabolism disorder. Although there had been studies to improve depression by regulating purinergic system, the mechanism of action was complex and needed to be sorted out. Recently, a large number of studies had found that the addition of exogenous purine metabolites adenosine, inosine and guanosine had a significant antidepressant effect, indicating that regulating the level of purine substances in purine metabolism could also improve depression, which was of great significance to the further study of the pathogenesis and treatment of depression. In view of this, this study reviewed the relationship between purinergic system or purine metabolism and depression, in order to provide a reference for the further study of the pathogenesis of depression.

  • Jing-wen CHEN, Xing-feng LIU, Bing CUI, Ping-ping LI
    Acta Pharmaceutica Sinica. 2021, 56(9): 2447-2455.

    Type 2 diabetes is a complex metabolic disease, accompanied by insulin resistance and elevated blood glucose. As the disease progresses, hyperglucagonemia will occur. Glucagon has a significant effect on glucose increase and energy expenditure. In recent years, several glucagon receptor (GCGR) antagonists were developed. They lowered blood glucose in clinical studies, along with side effects, such as increased blood lipids and elevated liver transaminase. In order to solve these problems, glucagon like peptide 1 receptor (GLP-1R)/GCGR co-agonists were developed, which not only lower blood glucose, but also reduce weight and promote lipolysis. In this review, we will focus on the biological effects of glucagon, the treatments of GCGR antagonists, and GLP-1R/GCGR co-agonists on type 2 diabetes.

  • Ying HAN, Guo-lan WEI, Nan MI, Lin-feng GUO, Chun-yun HU, Shuang LI, Lü-cun BI
    Acta Pharmaceutica Sinica. 2021, 56(9): 2389-2393.

    A fast and sensitive UPLC-MS/MS method was established for the direct quantification of insulin aspart in human plasma. The plasma samples were extracted by solid phase extraction (SPE), an ESI ion source was used and operated in the positive ion mode with multiple reaction monitoring (MRM). Bovine insulin was chosen as internal standard and the chromatographic separation of insulin aspart was performed on Waters ACQUITY UPLC CSH C18 column (50 mm×2.1 mm, 1.7 μm). A mixture of acetic acid aqueous solution and acetonitrile with acetic acid at a flow rate of 0.6 mL·min-1 in gradient elution mode was employed as mobile phase. We found that the method was validated over the range of 0.200-10.0 ng·mL-1 for insulin aspart and showed excellent linearity. The intra-and inter-assay accuracy and precision were below 14.5% and the recovery was 36.7%-41.7% over the three concentration levels evaluated. The UPLC-MS/MS method was selective, accurate, sensitive and robust, and the method was successfully applied in supporting the pharmacokinetic research of two insulin aspart injections (Test Product and NovoRapid?) in heathy male subjects. This clinical trial was approved according to the Ethics Committee of West China Hospital, Sichuan University (2017 Clinical Trial (Western Medicine) Approval (148)).

  • Fu-jiang WANG, Peng-fei TU, Ke-wu ZENG, Yong JIANG
    Acta Pharmaceutica Sinica. 2021, 56(9): 2528-2535.

    Modern pharmacological studies have shown that Cistanche deserticola (C. deserticola) has a protective effect on the liver, but its active fraction and mechanism are not clear. In order to identify the effective fraction of C. deserticola Y. C. Ma, an acute alcoholic liver injury model in mice was established with 56-proof Erguotou and different fractional extracts of C. deserticola Y. C. Ma (total glycosides, polysaccharides, and oligosaccharides) were administered. After 14 days of oral administration, liver pathology and lipid deposition were measured and the expression of nuclear factor E2-related factor (Nrf-2), kelch-like ECH-associated protein-1 (Keap-1), and plasmalemma vesicle-associated protein-1 (PV1) were measured by immunofluorescence. The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), endotoxin (ET), diamine oxidase (DAO), and D-lactic acid (D-LA) in serum, and superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), and malondialdehyde (MDA) in liver were measured by ELISA. All animal experiments were carried out with approval of the Experimental Animal Welfare Ethics Committee of the Peking University Health Science Center. The results show that the total glycosides of C. deserticola Y. C. Ma (400 mg·kg-1) could decrease liver pathology, decrease serum endotoxin, diamine oxidase, and D-lactic acid, and reduce hepatic lipid deposition. Total glycosides also promoted Nrf-2 transfer into the nucleus and decreased the expression of Keap-1 and PV1. In summary, the total glycosides of C. deserticola Y. C. Ma had a protective effect in acute alcoholic liver injury and the mechanism may be related to the activation of the Nrf-2/Keap-1 pathway, improvement of intestinal wall integrity, and inhibition of the transport of harmful substances into the liver.

  • Zheng CAI, Cai JIA, Jian-cheng WANG, Zuo-wen ZHANG, Lei WU
    Acta Pharmaceutica Sinica. 2021, 56(9): 2522-2527.

    Nanotechnology has been widely used in the field of pharmaceutics. In recent years, research projects related to nanotechnology account for a high proportion (nearly 90%) in the application and funded projects of pharmaceutics (application code is H3408) of National Natural Science Foundation of China (NSFC). In addition, there are many other research directions in the field of pharmaceutics. This paper makes statistics and analysis on the research projects of pharmaceutics without nanotechnology funded by NSFC from 2001 to 2020, so as to provide reference for the pharmaceutical researchers to reasonably choose research direction.

  • Hong-liang WANG, Wu-jun DONG, Lei CHEN, Jun YE, Yan-bao WANG, Yu-ling LIU
    Acta Pharmaceutica Sinica. 2021, 56(9): 2513-2521.

    Tert-butanol is an organic solvent, widely used in the medical field and chemical industry. It could be characterized by high crystallization temperature and vapor pressure. It could be easily sublimed and removed during the freeze-drying process. This review mainly describes the use of tert-butanol in the lyophilized formulations of poorly soluble drugs, the lyophilization solvent of porous structure productions, and as an ice crystal growth guider. In addition, the application of tert-butanol in nano drugs and aerogels has also been reviewed, as well as the current research progress in its quality and safety.

  • Tian ZHANG, Jiao CHEN, Rui-ping JIANG, Meng ZOU, Tie-chui YANG, Shao-bing FU, Jia-yu ZHOU, Hai LIAO
    Acta Pharmaceutica Sinica. 2021, 56(9): 2577-2583.

    The molecular identification of Fritillaria taibaiensis and its relatives was studied by real-time PCR with a TaqMan-MGB probe. DNA was extracted from F. taibaiensis and its relatives. According to the sequence of ITS1 region, the mutation sites of F. taipaiensis and its related species were identified by MEGA7.0 software. The specific primers (a pair) and a TaqMan-MGB probe were designed by Primer Premier 6.0 software. In the Roche LightCycler 96 system, the lowest limit of detection for F. taipaiensis DNA template was 0.002 39 ng·μL-1, and the optimal Tm value range was 60 and 61℃. Specificity identification showed that the method had good specificity for F. taipaiensis, as it could be distinguished from other 13 different Fritillaria species including F. unibracteata. Since this method could accurately identify F. taipaiensis and its related species, it provides technical support for rational development of F. taipaiensis resources, management of Chinese medicinal market and supervision of raw materials in Chinese medicine manufacturing enterprises.