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Frontiers in Pharmacology,2023年

Dongqian Yang, Xiaohua Liu, Jing Li, Jing Xie, Liping Jiang

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Toxoplasma gondii (T. gondii) is a nucleated intracellular parasitic protozoan with a broad host selectivity. It causes toxoplasmosis in immunocompromised or immunodeficient patients. The currently available treatments for toxoplasmosis have significant side effects as well as certain limitations, and the development of vaccines remains to be explored. Animal venoms are considered to be an important source of novel antimicrobial agents. Some peptides from animal venoms have amphipathic alpha-helix structures. They inhibit the growth of pathogens by targeting membranes to produce lethal pores and cause membrane rupture. Venom molecules generally possess immunomodulatory properties and play key roles in the suppression of pathogenic organisms. Here, we summarized literatures of the last 15 years on the interaction of animal venom peptides with T. gondii and attempt to explore the mechanisms of their interaction with parasites that involve membrane and organelle damage, immune response regulation and ion homeostasis. Finally, we analyzed some limitations of venom peptides for drug therapy and some insights into their development in future studies. It is hoped that more research will be stimulated to turn attention to the medical value of animal venoms in toxoplasmosis.

    Frontiers in Pharmacology,2023年

    Da-Yong Zheng, Ying Cui, Dailin Wu, Zhenjie Zhuang, Tianqi Gao, Dan Huang, Yan Zhao, Yi Yuan, Jing Li, Ying Tang

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    Tumor-associated macrophages (TAMs) are essential components of the immune cell stroma of hepatocellular carcinoma. TAMs originate from monocytic myeloid-derived suppressor cells, peripheral blood monocytes, and kupffer cells. The recruitment of monocytes to the HCC tumor microenvironment is facilitated by various factors, leading to their differentiation into TAMs with unique phenotypes. TAMs can directly activate or inhibit the nuclear factor-κB, interleukin-6/signal transducer and signal transducer and activator of transcription 3, Wnt/β-catenin, transforming growth factor-β1/bone morphogenetic protein, and extracellular signal-regulated kinase 1/2 signaling pathways in tumor cells and interact with other immune cells via producing cytokines and extracellular vesicles, thus affecting carcinoma cell proliferation, invasive and migratory, angiogenesis, liver fibrosis progression, and other processes to participate in different stages of tumor progression. In recent years, TAMs have received much attention as a prospective treatment target for HCC. This review describes the origin and characteristics of TAMs and their mechanism of action in the occurrence and development of HCC to offer a theoretical foundation for further clinical research of TAMs.

      Frontiers in Pharmacology,2023年

      Jing Li, Weikun Qu, Jie Bai, Shuai Wang, Yilin Che

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      Background: Humans with hypertensive heart disease are more likely to experience heart failure, arrhythmia, myocardial infarction, and sudden death, and it is crucial to treat this condition. Fucoidan (FO) is a natural substance derived from marine algae that has antioxidant and immunomodulatory activities. FO has also been shown to regulate apoptosis. However, whether FO can protect against cardiac hypertrophy is unknown.Methods: We investigated the effect of FO in hypertrophic models in vivo and in vitro. C57BL/6 mice were given an oral gavage of FO (300 mg/kg/day) or PBS (internal control) the day before surgery, followed by a 14-day infusion of Ang II or saline. AC-16 cells were treated with si-USP22 for 4 h and then treated with Ang II (100 nM) for 24 h. Systolic blood pressure (SBP) was recorded, echocardiography was used to assess cardiac function, and pathological changes in heart tissues were assessed by histological staining. Apoptosis levels were detected by TUNEL assays. The mRNA level of genes was assessed by qPCR. Protein expression was detected by immunoblotting.Results: Our data showed that USP22 expression was lowered in Ang II-infused animals and cells, which could promote cardiac dysfunction and remodeling. However, treatment with FO significantly upregulated the expression of USP22 and reduced the incidence of cardiac hypertrophy, fibrosis, inflammation, and oxidative responses. Additionally, FO treatment lowered p53 expression and apoptosis while increasing Sirt 1 and Bcl-2 expression.Conclusion: By reducing the level of Ang II-induced apoptosis through the regulation of USP22/Sirt 1 expression, FO treatment might improve cardiac function. According to this study, FO might be potential targeted approach for treating heart failure.

        Frontiers in Pharmacology,2023年

        Jinhui Liu, Xuhui Zhou, Yonglong Chang, Kechao Nie, Haixia Yan, Jing Li, Sifang Zhang, Qinling Ou

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        Background: Colorectal cancer (CRC) is a prevalent malignancy affecting the digestive tract, and its incidence has been steadily rising over the years. Surgery remains the primary treatment modality for advanced colorectal cancer, complemented by chemotherapy. The development of drug resistance to chemotherapy is a significant contributor to treatment failure in colorectal cancer. Nanodrug delivery systems (NDDS) can significantly improve the delivery and efficacy of antitumor drugs in multiple ways. However, there is a lack of visualization of NDDS research structures and research hotspots in the field of colorectal cancer, and the elaboration of potential research areas remains to be discovered.Objective: To comprehensively explore the current research status and development trend of NDDS in CRC research.Methods: Bibliometric analysis of articles and reviews on NDDS for CRC published between 2002 and 2022 using tools including CiteSpace, VOSviewer, R-bibliometrix, and Microsoft Excel was performed.Results: A total of 1866 publications authored by 9,870 individuals affiliated with 6,126 institutions across 293 countries/regions were included in the analysis. These publications appeared in 456 journals. Abnous Khalil has the highest number of publications in this field. The most published journals are the International Journal of Nanomedicine, International Journal of Pharmaceutics, and Biomaterials. Notably, the Journal of Controlled Release has the highest citation count and the third-highest H-index. Thematic analysis identified “inflammatory bowel disease”,“ “oral drug delivery," and “ulcerative colitis” as areas requiring further development. Keyword analysis revealed that “ulcerative colitis,” “exosomes,” and “as1411”have emerged as keywords within the last 2 years. These emerging keywords may become the focal points of future research.Conclusion: Our findings reveal the current research landscape and intellectual structure of NDDS in CRC research which helps researchers understand the research trends and hot spots in this field.

          Frontiers in Pharmacology,2023年

          Yifan Zhang, Yuchen Xie, Jing Li, Shun Yao, Siwei Liang, Taoqing Wu, Yongmei Shen

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          Background: As an important medicinal insect, Periplaneta americana (PA) has been applied for the treatment of wounds, burns, and ulcers with fewer side effects and a reduced recurrence rate, which provides great potential for developing new drugs based on its active constituents.Materials and methods: The main chromatographic peaks determined by high performance liquid chromatography (HPLC) in the PA concentrated ethanol-extract liquid (PACEL) were separated, purified, and identified by semi-preparative LC, mass spectrum, and 1H NMR spectroscopic analysis. The biological activities of the identified compounds were investigated by methylthiazolyldiphenyl-tetrazolium bromide (MTT) method based on in vitro human skin fibroblasts (HSF) and in vivo experiments based on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) mouse model. Furthermore, RT-qPCR of six genes related to inflammation or intestinal epithelial cell proliferation was employed to investigate the molecular mechanism of the indole analogues recovering UC in mice.Results: Five indole analogues were purified and identified from PACEL, including tryptophan (Trp), tryptamine (pa01), 1,2,3,4-tetrahydrogen-β-carboline-3-carboxylic acid (pa02), (1S, 3S)-1-methyl-1,2,3,4-tetrahydrogen-β-carboline-3-carboxylic acid (pa03), and (1R, 3S)-1-methyl-1,2,3,4-tetrahydrogen-β-carboline-3-carboxylic acid (pa04), among which the pa02 and pa04 were reported in PA for the first time. In vitro and in vivo experiments showed that PACEL, Trp, and pa02 had promoting HSF proliferation activity and intragastric administration of them could alleviate symptoms of weight loss and colon length shortening in the UC mice. Although recovery activity of the compound pa01 on the colon length was not as obvious as other compounds, it showed anti-inflammatory activity in histological analysis. In addition, The RT-qPCR results indicated that the three indole analogues could alleviate DSS-induced intestinal inflammation in mice by inhibiting pro-inflammatory cytokines (MMP7, IL1α) and down-regulating BMP8B expression.Conclusion: This study reported the isolation, purification, structure identification, and biological activity of the active indole analogues in PACEL. It was found for the first time that the PA extract contained many indole analogues and Trp, which exhibited good proliferation activity on HSF fibroblasts as well as anti-UC activity in mice. These indole analogues probably are important components related to the pharmacological activity in PA.