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  • Yu-bei GONG, Shao-guang LI, Yu-lu HONG, De-hui XIE, Shan-shan ZHENG, Xuan-rong SUN
    Acta Pharmaceutica Sinica. 2022, 57(4): 952-962.

    The microbiome is a significant participant and driver of cancer development. Using traditional methods (such as antibiotics, probiotics, and microbiota transplantation) to regulate the microbiome has been proven to improve the therapeutic effect of cancer. But this type of method also has many limitations, such as the indirect damage to the symbiotic microbiota and the consistency of methodology. There is an urgent need to develop new technologies to solve these problems. Considering the success of nanotechnology in the field of cancer diagnosis and treatment, the use of nanotechnology to regulate the interaction between the microbiome and the tumor microenvironment is also expected to provide new and effective strategies for cancer treatment. In this review, we summarized the characteristics and advantages of various generations of nanotechnology, and reviewed the recent research related to the application of nanotechnology intervention to regulate the microbiome and its metabolites in cancer diagnosis and treatment, and discussed the challenges and future development prospects of this emerging field.

  • Yi WANG, Yan-Jie ZHAO, Shuai LI
    Acta Pharmaceutica Sinica. 2022, 57(4): 990-1001.

    G protein-coupled receptors (GPCRs), the largest family of transmembrane receptors in the human, contain seven transmembrane helices, and are usually regarded as critical drug targets because of their key roles in multiple diseases. Currently, 30%-40% approved drugs target GPCRs. Nanobodies (also known as single domain antibodies) are important research tools for GPCRs due to their small molecular weight, good biochemical properties and high affinity for "cracks or cavities". In addition, nanobodies have long complementarity determining region 3 (CDR3) loops which can be inserted deeply into GPCRs ligand binding pockets, efficiently binding to the folds. This review summarizes the characteristics of nanobodies and their applications in GPCRs research and briefly introduces the current identification routes of targeted GPCRs nanobodies, which could provide new idea and method for applications of nanobodies in GPCRs research.

  • Long HUANG, Wen ZENG, Bing XU, Can-yang ZHANG, Shao-hua MA, Chong ZHANG, Yi WANG, Xin-hui XING
    Acta Pharmaceutica Sinica. 2022, 57(4): 976-989.

    Polysaccharides as one of the most common drug delivery materials have the excellent advantages, such as diverse natural sources, high biocompatibility and multi-functions. Polysaccharides have been investigated and widely used in food industry, pharmaceutical and medical fields especially in the targeted oral drug delivery for colonic diseases treatment with important research values and great potential applications. Inspired by the unique properties of polysaccharides, researchers around the world have developed the cross-linked nanoparticles, self-assembled nanoparticles and hydrogels, focusing on various drug delivery strategies such as pH-sensitive, microbial enzyme-responsive, reactive oxygen species-responsive, mucoadhesive and receptor-targeted. Exhilaratingly, the polysaccharides-based therapeutics have shown high efficacy for the treatment of digestive tract diseases, such as colitis or colonic cancer. Herein, we summarized the research progress of polysaccharides-based targeted oral drug delivery systems for colonic diseases treatment, and discussed the perspectives of the researches and application development in future.

  • Ya-rui YU, Meng-ying LIU, Jiao HUANG, Jing HUANG
    Acta Pharmaceutica Sinica. 2022, 57(4): 1080-1084.

    In order to study the chemical composition of Osmanthus fragrans var. thunbergii, the chemical constituents of the dried flower of O. fragrans var. thunbergii were studied. From the 95% ethanol extract of the dried flower, a new monoterpene (1), along with seven known monoterpenes, sesquiterpenes and phenethyl alcohols (2-8), was isolated and purified by silica gel, polyamide, and preparative reversed-phase HPLC chromatography methods. Their structures were identified by 1D-NMR (1H NMR, 13C NMR, DEPT), 2D-NMR (HSQC, HMBC, 1H-1H COSY, NOESY), HR-ESI-MS, IR, UV, and its physical and chemical properties as: methyl (R, E)-2-(5-ethylidene-2-oxotetrahydro-2H-pyran-4-yl) acrylate (1), (R, E)-2, 6-dimethyloct-3, 7-dien-2, 6-diol (2), (6R)-2, 6-dimethyloct-7-en-2, 3, 6-triol (3), 2, 4, 4-trimethyl-3-(3-oxobutyl)-cyclohex-2-en-1-one (4), (S)-2, 4, 4-trimethyl-3-(3-hydroxybutyl)-cyclohex-2-en-1-one (5), (R, E)-2, 4, 4-trimethyl-3-(3-hydroxybut-1-en-1-yl)-cyclohex-2-en-1-one (6), (S, E)-3, 5, 5-trimethyl-4-hydroxy-4-(3-oxobut-1-en-1-yl)-cyclohex-2-en-1-one (7), and 2-p-acetoxyphenylethanol (8). 1 is a new compound, 2-8 were isolated from the plant of Osmanthus fragrans var. thunbergii for the first time.

  • Jia-ling CHENG, Jun YE, Hong-liang WANG, Yan-fang YANG, Zhi-yang CHEN, Hang ZHOU, Yu-ling LIU
    Acta Pharmaceutica Sinica. 2022, 57(4): 1002-1009.

    Silk fibroin is a kind of natural biodegradable polymer, which is stable, non-toxic, cheap and easy to obtain, and has no inflammatory reaction. Silk fibroin shows satisfactory degradability and biocompatibility, widely used as a promising material for biological tissue engineering and drug delivery carrier in the biomedical field. This review introduces the structure and constituent of silk fibroin, summarizes the research progress and methods of evaluating biodegradability and biocompatibility in vivo and in vitro, which provides reference for further research and application of silk fibroin.

  • Zi-hao ZHU, Wen-xuan ZHANG, Tian-lei LI, Song WU
    Acta Pharmaceutica Sinica. 2022, 57(4): 892-902.

    Tuberculosis (TB) is an enduring threat to global health. The epidemic persists with growing drug resistance, especially for extensively drug-resistant TB. Therefore, the treatment for TB and its associated multidrug resistance has been an ongoing challenge. Due to the greater attention and investment in the elimination of this disease, significant progress has been achieved. Bedaquiline, delamanid, and pretomanid have been approved for the clinical use. In addition, two dozens new anti-TB drugs are currently in clinical testing. China has contributed four new drugs TBI-223, TBI-166, aulimanid, and WX-081. The aim of this review is to summarize the recent advances in anti-TB drug development. Based on the different clinical stages of these anti-TB drugs, we mainly focus on mechanism of action, in vitro and in vivo pharmacological studies, pharmacokinetics and clinical studies.

  • Long-yu MA, Shan FENG, Shen ZHANG, Jin-jin SHENG, Chao-qun LIU
    Acta Pharmaceutica Sinica. 2022, 57(4): 1155-1162.

    The emergence of antibiotic-resistant strains seriously reduces the efficiency of traditional antibiotic therapy. The development of a new alternative antibiotic method to effectively eliminate this bacterial infection has become a critical issue. Photothermal therapy (PTT) has shown many advantages in tissue penetration, spatiotemporal specificity, no drug resistance and broad-spectrum antimicrobial ability. However, extremely high temperature (55-65 ℃) is needed to achieve highly efficient bactericidal effect during PTT treatment process. Thus, this procedure will inevitably cause collateral damage to normal tissues. Silver nanoparticles (AgNPs) are one of the most commonly used broad-spectrum antimicrobial agents. Its antimicrobial activity is mainly derived from the release of silver ions (Ag+). However, excessive AgNPs not only would cause toxic to the body, but also waste precious metals. In this study, oxidized mesoporous carbon nanospheres (OMCN) were used as photothermal materials to prepare OMCN-Ag+ composites. The composite material can improve the antibacterial activity, reduce the waste of metal Ag and decrease the toxic and side effects. Moreover, the precisely controlled mild heat can overcome the shortcoming such as the damage to normal tissue caused by the excessive temperature during traditional photothermal antimicrobial process. The antimicrobial treatment system exhibits a good biocompatibility both in vitro and in vivo. Specially, the designed nanosytem can effectively eliminate the bacteria from the infected wound, subsequently promoting the process of wound healing. All animal experiments were carried out with approval of the Animal Experiment Ethics Committee of Henan University.

  • Yue YANG, Hai-yan WANG, Ye SUN, Tao SUN, Chen JIANG
    Acta Pharmaceutica Sinica. 2022, 57(4): 963-975.

    As a kind of tumor immunotherapy, tumor vaccine provides a new strategy for cancer treatment. With nano-biomimetic materials to encapsulate the tumor antigens, the construction of nano-biomimetic tumor vaccine can target the tumor and release antigens, with high efficiency and safety. Therefore, nano-biomimetic vaccine has become a hot research topic. Based on this review, several new nano-biomimetic nanoparticles are summarized, and the clinical applications of the nano-biomimetic vaccine combined with other therapeutic strategies are introduced.

  • De-sen LI, Yue-gui CHEN, Kai GUO, Yi LING, Yan LIU, Sheng-hong LI
    Acta Pharmaceutica Sinica. 2022, 57(4): 931-942.

    Sesterterpenoids, composed of five isoprene units and biosynthetically derived from geranylfarnesyl diphosphate (GFDP), are a class of the precious terpenoids with approximately 1 300 natural products known to date. Natural sesterterpenoids are widely distributed and possess extreme structural complexity and diversity and remarkable biological activity. In recent decades, a series of important progresses have been made in sesterterpenoid biosynthesis with the development of genome mining and heterogeneous expression technologies. This paper mainly focuses on the advances in sesterterpenoid biosynthesis, including the biochemical functions and catalytic mechanisms of GFDP synthases, sesterterpene synthases and oxidases. This review would lay the foundation for in-depth investigation on the biosynthesis, biological activities and synthetic biology of sesterterpenoids.

  • Xiao-han XU, Xiao-li LI, Zhi-qiang TANG, Qian LIU, Jia LI, Zhen-hua LIU, Yong-qing ZHANG, Gao-bin PU
    Acta Pharmaceutica Sinica. 2022, 57(4): 1187-1192.

    Using Lonicera japonica genomic DNA as a template, we cloned Lonicera japonica U6 promoters. Four LjU6 promoters, 336, 708, 359 and 602 bp in length, were cloned by PCR from Lonicera japonica genomic DNA. PlantCARE analysis found that the four promoters contained typical promoter cis-elements, such as a TATA box and CAAT box, and contained regulatory elements related to light response and stress response. After the cloning products were sequenced, the LjU6 promoter was ligated to the pBI121 vector carrying the β-glucuronidase (GUS) gene to construct four LjU6-pBI121 fusion expression vectors. Nicotiana tabacum leaves were transformed by the Agrobacterium transient transformation method and GUS histochemical staining was performed on the leaves. The staining results showed that LjU61-F1 had the highest transcriptional activity. This study thus identified a U6 promoter with high transcriptional activity, providing a basis for the establishment of CRISPR/Cas9 genome editing technology in Lonicera japonica.