ABSTRACT
新冠病毒感染疫情严重威胁着世界各国人民的生命健康。目前，对病毒感染的防治研究主要集中在抑制病毒与分子受体的结合上。AXL作为新发现的严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）受体，在协助病毒感染人体呼吸系统中发挥着重要作用，是未来临床干预的潜在靶点。本研究对已发表的单细胞测序数据进行整理和分析，发现AXL在年轻人肺细胞中的表达水平明显高于老年人。人胚肺二倍体成纤维细胞（2BS）是衰老研究的公认细胞株。本文采用2BS细胞构建复制性细胞衰老模型，发现年轻细胞中AXL的蛋白水平明显高于衰老细胞，据此推测年轻人感染的风险可能更高，需要注意防护。我们发现一种羊栖菜褐藻多糖硫酸酯组分（SFW-3）可显著下调年轻2BS细胞中AXL的表达水平，表明SFW-3具有一定的抗SARS-CoV-2感染的研究价值，同时表明2BS细胞株也可作为潜在的SARS-CoV-2体外感染模型。
Subject(s)
Humans , SARS-CoV-2 , Sargassum/metabolism , Diploidy , Sulfates/metabolism , COVID-19 , Polysaccharides/pharmacology , LungABSTRACT
Programmed cell death ligand 1 (PD-L1)/programmed cell death protein 1 (PD-1) cascade is an effective therapeutic target for immune checkpoint blockade (ICB) therapy. Targeting PD-L1/PD-1 axis by small-molecule drug is an attractive approach to enhance antitumor immunity. Using flow cytometry-based assay, we identify tubeimoside-1 (TBM-1) as a promising antitumor immune modulator that negatively regulates PD-L1 level. TBM-1 disrupts PD-1/PD-L1 interaction and enhances the cytotoxicity of T cells toward cancer cells through decreasing the abundance of PD-L1. Furthermore, TBM-1 exerts its antitumor effect in mice bearing Lewis lung carcinoma (LLC) and B16 melanoma tumor xenograft
ABSTRACT
Programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) blocking therapy has become a major pillar of cancer immunotherapy. Compared with antibodies targeting, small-molecule checkpoint inhibitors which have favorable pharmacokinetics are urgently needed. Here we identified berberine (BBR), a proven anti-inflammation drug, as a negative regulator of PD-L1 from a set of traditional Chinese medicine (TCM) chemical monomers. BBR enhanced the sensitivity of tumour cells to co-cultured T-cells by decreasing the level of PD-L1 in cancer cells. In addition, BBR exerted its antitumor effect in Lewis tumor xenograft mice through enhancing tumor-infiltrating T-cell immunity and attenuating the activation of immunosuppressive myeloid-derived suppressor cells (MDSCs) and regulatory T-cells (Tregs). BBR triggered PD-L1 degradation through ubiquitin (Ub)/proteasome-dependent pathway. Remarkably, BBR selectively bound to the glutamic acid 76 of constitutive photomorphogenic-9 signalosome 5 (CSN5) and inhibited PD-1/PD-L1 axis through its deubiquitination activity, resulting in ubiquitination and degradation of PD-L1. Our data reveals a previously unrecognized antitumor mechanism of BBR, suggesting BBR is small-molecule immune checkpoint inhibitor for cancer treatment.
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Objective To investigate the expression profile of long non - coding RNAs(lncRNAs) in acute kidney injury (AKI) rats upon astragaloside IV(AS - IV) treatment. Methods Eight male SD rats were selected and randomly divided into two groups. AKI model group(group 1):4 rats were subjected to ischemia - reperfusion(I/ R);AS - Ⅳ pretreatment group (group 2):4 rats were orally administered AS - Ⅳ for 7 days prior to I/ R. Renal tissues were collected after I/ R treatment of 24h,total RNA was extracted from renal tissues and tested for quality. Sequencing experiments were carried out after being qualified. The threshold set for up - and down - regulated genes was a fold change(group1 / group2)≥2 and P≤0. 05. Afterwards,GO analysis and KEGG analysis were used to determine the roles that these differentially expressed mRNAs played in these GO terms or pathways. Results Two hundred and thirty - two lncRNAs were differentially expressed(127 lncRNAs were up - regulated and 105 lncRNAs were down -regulated). Three hundred and forty - one mRNAs were differentially expressed(178 mRNAs were up - regulated and 163 mRNAs were down - regulated). GO analysis indicated that differentially expressed mRNAs were mainly involved in biological processes such as nucleosome assembly,chromatin assembly,nucleosome organization,chromatin assembly or disassembly and DNA conformation change. GO analysis indicated that differentially expressed mRNAs were mainly involved in cellular components such as nucleosome,protein - DNA complex,nuclear chromatin,chromatin and nuclear nucleosome. GO analysis indicated that differentially expressed mRNAs were mainly involved in molecular functions such as protein heterodimerization activity,protein dimerization activity,DNA binding,nucleic acid binding. Signal pathway analysis indicated that lncRNAs and mRNAs were involved in systemic lupus erythematosus,alcoholism and viral carcinogenesis. Conclusion LncRNAs expression differed significantly in renal tissues of AKI model group and AS - Ⅳ preconditioning group. Study of the biological functions and pathways of these lncRNAs indicated that they may be involved in the mechanism of AS - Ⅳ ameliorated ischemic acute renal injury.
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OBJECTIVE:To preliminarily study the stability of 3 pieces of Chinese medicinal formula(CMF)after decoction, and provide reference for guaranteeing storage quality of decocted liquid and improving safety of drug use. METHODS:3 represen-tative formulas of Gegen Huangqin Huanglian decoction(A formula),Wuling powder(B formula)and Didang decoction(C for-mula)from Shanghan Zabing Lun were selected,the decocted liquid were stored under ambient temperature(25 ℃)and refrigerat-ed temperature (4 ℃) after decocting by automatic boiling-machine and packing. The microorganism,precipitation,pH and con-tents of total flavonoids,alkaloid,polysaccharide,total protein after 1,7,14,21,28 d were detected. RESULTS:Compared with the first day,contents of total flavonoids,polysaccharide in formula A at ambient temperature group were significantly in-creased on the 28th(P<0.05),content of polysaccharide in refrigerated temperature group was significantly increased(P<0.05). Content of polysaccharide in formula B at ambient temperature group was significantly decreased(P<0.05). The pH and content of total flavonoids in formula C at ambient temperature group and refrigerated temperature group were significantly increased (P<0.05 or P<0.01). Other indexes showed no obvious changes during the trial period. CONCLUSIONS:Under ambient temperature and refrigerated temperature,liquid ingredients of above decocted CMF will change when storing for 4 weeks. It indicates that the storage time of decocted CMF should not be more than 3 weeks.
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EZH2 is over-expressed in human colon cancer and is closely associated with tumor proliferation, metastasis and poor prognosis. Targeting and inhibiting EZH2 may be an effective therapeutic strategy for colon cancer. 3-Deazaneplanocin A (DZNep), as an EZH2 inhibitor, can suppress cancer cell growth. However, the anti-cancer role of DZNep in colon cancer cells has been rarely studied. In this study, we demonstrate that DZNep can inhibit the growth and survival of colon cancer HCT116 cells by inducing cellular senescence and apoptosis. The study provides a novel view of anti-cancer mechanisms of DZNep in human colon cancer cells.