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  • Jian-tao WANG, Hui-shan CENG, Zhen WEI, Liang CHEN
    Acta Pharmaceutica Sinica. 2021, 56(1): 224-230.

    This study aims to investigate the effect of baicalein on the metastasis of esophageal squamous cell carcinoma(ESCC) cells, and to elucidate the potential molecular mechanisms. Wound healing and Transwell migration and invasion assays were performed to detect the effect of baicalein on the migration and invasion of EC9706 and KYSE30 cells; the nude mice models of lung metastasis were applied to examine the function of baicalein in metastasis of ESCC by using KYSE30 cells. All animals were received humane care according to the Institutional Animal Care Guidelines approved by the Experimental Animal Ethical Committee of Henan University. Western blot assay was used to detect the protein levels of ERK/ELK-1/Snail signaling pathway. The data showed that baicalein significantly inhibited the migration and invasion of EC9706 and KYSE30 cells; Mechanistically, baicalein treatment led to a dramatically reduced expression of phosphorylated extracellular signal-regulated kinase 1/2(p-ERK1/2, T202/Y204), p-ETS-domain containing protein-1(p-ELK-1, S383), Snail, N-cadherin, and Vimentin, and a statistical increase of E-cadherin expression in EC9706 and KYSE30 cells; Furthermore, the inhibition of ERK1/2 by U0126 or siRNA remarkably enhanced the effect of baicalein on the above proteins. In summary, baicalein probably inhibits the migration, invasion, and metastasis of ESCC cells via blocking the ERK/ELK-1/Snail signaling pathway.

  • Xin CHEN, An LU, Xiang-yu WANG, Xiao-ling WANG, Ai-ping ZHENG, Jian-cheng WANG
    Acta Pharmaceutica Sinica. 2021, 56(1): 130-137.

    With the implementation of the two-child policy and the growing demand for child health, pediatric medication has been arousing widespread social concern. To develop the drugs suitable for children, including new compounds, new specifications and new dosage forms, is urgently required for pharmaceutical researchers. In this review, several technical bottlenecks for pediatric oral liquid preparations, as well as the novel strategies involved in drug nanocrystals, self-microemulsion, ion exchange resin and Pickering emulsion were discussed, which may be benefit to play a theoretical guiding role in the research and development of children's oral liquid formulation.

  • Kai-yun YAO, Hong-wan DING, Lin-yu CAO, Yin-ge GAO, Jian-jun ZHANG, Gui-bin WANG
    Acta Pharmaceutica Sinica. 2021, 56(1): 29-36.

    Depression is a serious mental illness with a high incidence. At present, we do not fully understand the specific pathological mechanisms of depression, and the efficacy of drug treatments is very limited. Recent studies have shown that epigenetic changes that occur in specific brain regions may be a key mechanism by which environmental factors to interact with individuals to influence the risk of depression. Therefore, drugs that target epigenetic regulation may become a new direction for the development of antidepressants. Histone deacetylase inhibitors (HDACi) are a class of compounds that inhibit histone deacetylase activity, which has been reported to be associated with depression; this article addresses the use of HDACi in preclinical studies, and their potential therapeutic role and limitations of use in depression.

  • Zhi-xiong LI, Guang-xu XIAO, Shuang HE, Huan-yi WANG, Yan ZHU
    Acta Pharmaceutica Sinica. 2021, 56(1): 231-243.

    As a Ginkgo biloba extract preparation, shuxuening injection has a unique advantage in the prevention and treatment of acute and subacute stroke, but its main active ingredient is still unclear. Using a subacute model of stroke in mice constructed earlier, we further explored the contribution and mechanism of the two main components of total ginkgo flavonol glycosides and total ginkgolides in facilitating the neurofunctional recovery in stroke-induced mice. The pharmacodynamics was mainly evaluated by neurobehavioral changes, cerebral infarction volume, blood-brain barrier permeability and brain edema. The pathway and targets were predicted by transcriptome and network pharmacology. Finally, the mechanism was verified at the mRNA and protein levels. The results showed that the beneficial effect of total ginkgolides was greater than that of total ginkgo flavonol glycosides in both the pharmacodynamics and the regulatory mechanism of granulocyte adhesion and diapedesis involving granulocyte colony-stimulating factor(G-CSF), macrophage-1 antigen(MAC-1) and E-selectin. These findings suggest that shuxuening injection may improve the prognosis for mice with subacute stroke by down-regulating GCSF-mediated granulocyte adhesion and diapedesis pathway mainly through the total ginkgolide components. This finding is expected to provide reference for optimizing prescription and searching for natural drugs for targeting the treatment of ischemic stroke prognosis. The animal experiments in this study followed the regulations of Animal Ethics Committee of Tianjin University of Traditional Chinese Medicine.

  • Ya-bin DUAN, Jun-bo ZHU, Jian-xin YANG, Xiang-yang LI
    Acta Pharmaceutica Sinica. 2021, 56(1): 50-60.

    The function of circulatory system, nervous system and endocrine system is significantly changed in hypoxic environments. These changes affect the absorption, distribution, metabolism, and excretion of drugs in the body. Drug metabolizing enzymes and transporters are the main factors affecting drug metabolism; microRNA(miRNA) can act directly on drug metabolizing enzymes and transporters and can regulate their genes through hypoxia-inducible factor, inflammatory cytokines, and nuclear receptors. This article reviews the effect of hypoxia on drug metabolizing enzymes and transporters and the mechanisms by which miRNA modulates these proteins and their expression during hypoxia.

  • De-wen KONG, Zi-ru YU, Qi-meng ZHOU, Guan-hua DU
    Acta Pharmaceutica Sinica. 2021, 56(1): 1-8.

    The α4β2-nicotinic acetylcholine receptor(nAChR) is a ligand-gated ion channel that is distributed throughout the nervous system. It is involved in the regulation of various neurotransmitters including acetylcholine, dopamine, γ-aminobutyric acid, and norepinephrine. α4β2-nAChR plays an important role in learning, memory, cognition, attention, inflammation, and pain. A large number of studies have shown that α4β2-nAChR is an important therapeutic target for neurological diseases such as Alzheimer's disease, Parkinson's disease, epilepsy, depression, nicotine dependence, pain, etc. It is an important target in the early diagnosis and curative effect detection of neurodegenerative diseases including Alzheimer's disease. This review summarizes the role, mechanisms and related drug research advances on α4β2-nAChR ligand drugs in neurological diseases, as well as providing a theoretical basis for identifying and developing more suitable α4β2-nAChR-related compounds.

  • Shan WANG, Ya-bing HUA, Xiang GAO, Hui ZHANG, Nan LIU, Jing GAO, Ai-ping ZHENG
    Acta Pharmaceutica Sinica. 2021, 56(1): 158-168.

    As a depot drug delivery system, injectable polylactide-polyglycolide(PLGA) sustained-release microspheres have been successfully used to treat many diseases since the first microsphere product Lupron depot was approved for marketing in the United States in 1989. It has the ability of long-term release in the body for several days to several months, which can not only reduce the times of administration, but also reduce the drug blood concentration fluctuations, significantly improve the safety and patient compliance. In vitro-in vivo correlation(IVIVC) makes the development of microspheres more possible. It can describe the dynamic information of drug release in vivo through the in vitro release behavior of microspheres, and can reduce the workload of each stage and shorten the time span while characterizing the performance of microspheres. IVIVC can provide guidance or support for drug development, production changes, supervision and management. This article summarizes the release mechanism of injectable PLGA sustained-release microspheres, common measurement methods and theories of in vitro and in vivo release. And we also focus on the establishment and application of IVIVC, especially A level IVIVC in the field of microsphere preparations, to provide a reference for further study on in vitro-in vivo correlation of microspheres.

  • Ting XIAO, Chen WANG, Shang-chen YAO, Yan-chun FENG, Chang-qin HU
    Acta Pharmaceutica Sinica. 2020, 55(12): 2854-2861.

    With the in-depth study of related substances and the development of consistency evaluation of generic drugs, relative correction factors are gaining increasing attention. By analyzing the domestic and foreign literature on correction factors in recent years, this paper describes the correction factor component, the current measurement method and its application. The rules and key points of use of an impurity correction factor and its determination and application are described, and some problems in its determination and application are discussed, providing a reference and basis for the standardization of research on impurity correction factors in the future.

  • Nan LIU, Na LI, Xiao-hua MA, Lin ZHU, Cheng-cheng SHI
    Acta Pharmaceutica Sinica. 2020, 55(12): 2793-2799.

    Long non-coding RNA (lncRNA) has a wide range of biological functions in epigenetic, cell cycle, cell differentiation and other life activities, and that affect the development and differentiation of immune cells and the maintenance of homeostasis in the immune system. CD4+ T cell subsets are heterogeneous cells with different functions, including promoting the proliferation and differentiation of T cells, B cells and other immune cells, and coordinating related functions between immune cells. Autoimmune disease (AID) is a chronic inflammatory disease caused by an autoantigen immune reaction. lncRNA and CD4+ T cell subsets are involved in the occurrence and progression of the disease. This article reviews the relationship between lncRNA and the differentiation of AID CD4+ T cell subsets.

  • Nuo-qi WANG, Xiu-ying YANG, Guan-hua DU
    Acta Pharmaceutica Sinica. 2020, 55(12): 2811-2817.

    Wound healing is a complex and highly regulated process to maintaining the skin barrier function. Wounds of diabetic patients are hard or even not healing. Non-healing diabetic foot ulcers can lead to lower-extremity amputations. Diabetic wound healing problem is the main complication that leads to high disability rate of diabetes and can threaten the lives in severe cases. The healing of skin wounds requires the synergy of multiple factors to restore the injured skin to its barrier function. The mechanisms that cause it difficult to heal diabetic wounds are complex, including oxidative stress, chronic inflammation, decreased neovascularization, peripheral neuropathy, and imbalance of extracellular matrix accumulation and remodeling. This review classifies mechanisms of diabetic wound healing and provides a reference for its further research.