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Non-small cell lung cancer (NSCLC) brain metastases present a significant treatment challenge due to limited drug delivery efficiency and severe adverse reactions. In this study, we address these challenges by designing a "on/off" switchable crosslinked paclitaxel (PTX) nanocarrier, BPM-PD, with novel ultra-pH-sensitive linkages (pH 6.8 to 6.5). BPM-PD demonstrates a distinct "on/off" switchable release of the anti-cancer drug paclitaxel (PTX) in response to the acidic extratumoral microenvironment. The "off" state of BPM-PD@PTX effectively prevents premature drug release in the blood circulation, blood-brain barrier (BBB)/blood-tumor barrier (BTB), and normal brain tissue, surpassing the clinical PTX-nanoformulation (nab-PTX). Meanwhile, the "on" state facilitates precise delivery to NSCLC brain metastases cells. Compared to nab-PTX, BPM-PD@PTX demonstrates improved therapeutic efficacy with a reduced tumor area (only 14.6%) and extended survival duration, while mitigating adverse reactions (over 83.7%) in aspartate aminotransferase (AST) and alanine aminotransferase (ALT), offering a promising approach for the treatment of NSCLC brain metastases. The precise molecular switch also helped to increase the PTX maximum tolerated dose from 25 mg/kg to 45 mg/kg This research contributes to the field of cancer therapeutics and has significant implications for improving the clinical outcomes of NSCLC patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Fusion with host cell membrane is the main mechanism of infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we propose that a new strategy to screen small-molecule antagonists blocking SARS-CoV-2 membrane fusion. Using cell membrane chromatography (CMC), we found that harringtonine (HT) simultaneously targeted SARS-CoV-2 S protein and host cell surface TMPRSS2 expressed by the host cell, and subsequently confirmed that HT can inhibit membrane fusion. HT effectively blocked SARS-CoV-2 original strain entry with the IC 50 of 0.217 μM, while the IC 50 in delta variant decreased to 0.101 μM, the IC 50 in Omicron BA.1 variant was 0.042 μM. Due to high transmissibility and immune escape, Omicron subvariant BA.5 has become the dominant strain of the SARS-CoV-2 virus and led to escalating COVID-19 cases, however, against BA.5, HT showed a surprising effectiveness. The IC 50 in Omicron BA.5 was even lower than 0.0019 μM. The above results revealed the effect of HT on Omicron is very significant. In summary, we characterize HT as a small-molecule antagonist by direct targeting on the Spike protein and TMPRSS2., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

With the rapid development of therapeutic monoclonal antibody drugs, it is increasingly difficult to meet clinical needs using traditional antibody purification techniques. In this study, epidermal growth factor receptor (EGFR)-SNAP-tag was expressed in HEK293 cells. Then we captured the EGFR-SNAP-tag from the cell membrane suspension onto a O 6 -benzylguanine-modified silica gel to prepare a new EGFR stationary phase as a bioactive material, which could specifically recognize its antibody in bio-samples. The EGFR stationary phase was systematically characterized via scanning electron microscopy, transmission electron microscopy, X-ray photoelectron spectroscopy, and fourier transform infrared spectroscopy. Then we used EGFR stationary phase to establish a new EGFR cell membrane chromatography (CMC) model. The EGFR/CMC-online-ion exchange chromatography (IEC)/high performance liquid chromatography (HPLC) was established for the efficient purification and specific identification of cetuximab, nituzumab, and panizumab from cell culture medium and human serum. The results show that the EGFR stationary phase prepared by one-step immobilized technique can maintain biological activity and stability like EGFR in cell membrane. The EGFR/CMC-online-IEC/HPLC method has a high specificity, accuracy and sensitivity. Therefore, it will present a valuable method for the purification, identification, and analysis of monoclonal antibody drugs., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Pseudo-allergic reactions occurred in patients administered drugs for the first time, seriously threaten man's survival. Due to the frequent reports of pseudo-allergic reactions to Danshen injection, in our previous study, isosalvianolic acid C in Danshen injection was found to trigger off mast cell degranulation. However, the direct involvement and the mechanisms underlying pseudo-allergic reactions have not been elucidated. In this study, the pseudo-allergic reactions induced by isosalvianolic acid C were confirmed by an ear swelling assay, a hindpaw swelling and extravasation assay in vivo and mast cell degranulation assays in vitro. We also evaluated whether the pseudo-allergic effect is related to MRGPRX2, Isosalvianolic acid C induced Ca 2+ mobilization was verified as MRGPRX2-related by Ca 2+ imaging using mouse peritoneal mast cells (both wild-type and MrgprB2 knockout mice), MRGPRX2-expressing HEK293 and MrgprB2-expressing HEK293 cells. MRGPRX2-related pseudo-allergic reactions induced by Isosalvianolic acid C were further confirmed by MrgprB2 knockout mice and MRGPRX2 knockdown mast cells both exhibited reduced isosalvianolic acid C-induced pseudo-allergic effects. Furthermore, both the frontal analysis and molecular docking assays showed that isosalvianolic acid C has a considerable affinity with MRGPRX2. Based on the above experiments, the western blot analyses were conducted, the results indicated that isosalvianolic acid C induced Ca 2+ mobilization and degranulation via the activation of PLC-γ and IP3R, and releasing chemokines via the activation of PLC-γ, PKC and P38. This study should alarm many clinicians that medicines containing isosalvianolic acid C might induce pseudo-allergic reactions, and it may provide guidance on safe dosage of these medicines in the process of production and use., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Kudiezi injection is a traditional Chinese medicine injection used widely in China to alleviate blood stasis and to stimulate blood circulation. Its use has been associated with a high rate of adverse effects including anaphylactoid reactions. In the present study, a two-dimensional system comprised of high expression Mas-related G protein-coupled receptor X2 cell membrane chromatography coupled online with HPLC-ESI-IT-TOF-MS was established, and used to screen and identify anaphylactoid components in kudiezi injection. Luteolin-7-O-glucuronide, apigenin-7-O-glucronide, luteoloside and luteolin were identified as the potential anaphylactoid components. The release of β-hexosaminidase and histamine from Laboratory of Allergic Disease 2 cells enabled evaluation of the anaphylactoid activities of these compounds in vitro. Both β-hexosaminidase and histamine release were enhanced markedly with increasing concentrations of the anaphylactoid components. The molecular docking assay showed excellent interactions between the potential anaphylactoid constituents and MRGPRX2. In general, the two-dimensional system developed in this study is effective in screening for the anaphylactoid components in Kudiezi injection., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Corydalis Thizoma,or Yuanhu in China, is a common herbal drug used for thousands of years as analgesic in Chinese medicine that has been reported to have potential anti-angiogenic effects. In this study, a VEGFR/cell membrane chromatography (VEGFR/CMC) coupled with HPLC- ESI-IT-TOF-MSn system was developed and successfully applied for identifying active components from YuanHu extract acting on VEGFR. We identified tetrahydropalmatine and corydaline as bioactive components with VEGFR activity, thus confirming their inhibitory activity on VEGFR engineered HEK293 cell growth by MTT assay. The activity of tetrahydropalmatine and corydaline was compared with the positive control sorafenib in a range of concentration from 6.25 to 50.0μM, showing a dose-dependent inhibitory trend. These results indicate that the VEGFR/CMC coupled with HPLC- ESI-IT-TOF-MSn system can purify and identify specific bioactive components from complex systems, thus representing a promising tool for screening molecules active towards VEGFR from natural herbs., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Shuanghuanglian (SHL) injection is a traditional Chinese medicine (TCM) injection widely used in China to treat influenza, tonsillitis, bronchitis, and faucitis. Adverse drug reactions (ADR) of SHL injection, majorly manifested as allergic reactions, were among the leading causes of death from TCM injection. In this study, an RBL-2H3/CMC online LC/MS system was established to screen and identify allergenic components in SHL injection, by which Baicalin was identified as a potential allergenic component. Allergenic activities of baicalin were investigated in RBL-2H3 cell degranulation and β-hexosaminidase release tests in vitro. Our results showed that baicalin dose-dependently induced RBL-2H3 cell degranulation and β-hexosaminidase release in the range of 0-50μg/ml. The RBL-2H3/CMC online LC/MS system developed in this study may potentially be used to screen allergenic components in other TCM injections., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Benign prostatic hyperplasia (BPH) is a common disease in elderly men. The main treatment for BPH is α-adrenergic antagonists and 5α-reductase inhibitors. In this study, a two-dimensional (2D) α₁A cell membrane chromatography (CMC) online liquid chromatography/mass spectrometry system was built. Fructus Piperis, a traditional Chinese medicine and food homolog, was assayed with this 2D system. Piperine was identified as the active compound acting on α₁A receptors. A competitive binding assay and molecular docking assay were performed to investigate the binding sites and the affinity of piperine for the α₁A receptor. The results of the competitive binding assay (dissociation equilibrium constant of tamsulosin was 1.43 × 10(-6)M and piperine was 2.13 × 10(-6)M) and molecular docking assay (total score for tamsulosin binding with the α₁A receptor was 6.9719, and for piperine it was 4.4891) corresponded with the retention time of tamsulosin and piperine on the α₁A/CMC column., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Radix scutellariae is a traditional Chinese medicine (TCM) and has many pharmacological effects, including antiviral, antibacterial, antifungal, antipyretic, hypotensive, anti-inflammatory and anti-anaphylaxis effects. However, few studies have screened the active compounds in this complex product for tumor therapy. In this study, a two-dimensional online method was developed to screen the active compounds from Radix scutellariae acting on the epidermal growth factor receptor. The screening results showed that wogonin from Radix scutellariae was the targeted component which acted on epidermal growth factor receptor specificity. The in vitro inhibitory activity of wogonin on the viability of cells with high epidermal growth factor receptor expression was tested using the MTT assay. In the dosage range of 0.40-50.0 μM, inhibition of HEK293/EGFR by wogonin was 8.94 ± 0.2, 20.64 ± 5.10, 34.16 ± 5.90 and 69.03 ± 7.80 at the concentrations of 0.4 × 10(-6), 2 × 10(-6), 10 × 10(-6) and 50 × 10(-6) molL(-1), respectively. These results showed that wogonin inhibited the growth of cells with high epidermal growth factor receptor expression in a dose-dependent manner., (Copyright © 2012 Elsevier B.V. All rights reserved.)