The surface plasmon resonance (SPR) biosensor technology is a novel optical analysis method for studying intermolecular interactions. Owing to in-depth research on traditional Chinese medicine (TCM) in recent years, comprehensive and specific identification of components and target interactions has become key yet difficult tasks. SPR has gradually been used to analyze the active components of TCM owing to its high sensitivity, strong exclusivity, large flux, and real-time monitoring capabilities. This review sought to briefly introduce the active components of TCM and the principle of SPR, and provide historical and new insights into the application of SPR in the analysis of the active components of TCM.

miR-135 is a highly conserved miRNA in mammals and includes miR-135a and miR-135b. Recent studies have shown that miR-135b is a key regulatory factor in cardio-cerebrovascular diseases. It is involved in regulating the pathological process of myocardial infarction, myocardial ischemia/reperfusion injury, cardiac hypertrophy, atrial fibrillation, diabetic cardiomyopathy, atherosclerosis, pulmonary hypertension, cerebral ischemia/reperfusion injury, Parkinson's disease, and Alzheimer's disease. Obviously, miR-135b is an emerging player in cardio-cerebrovascular diseases and is expected to be an important target for the treatment of cardio-cerebrovascular diseases. However, the crucial role of miR-135b in cardio-cerebrovascular diseases and its underlying mechanism of action has not been reviewed. Therefore, in this review, we aimed to comprehensively summarize the role of miR-135b and the signaling pathway mediated by miR-135b in cardio-cerebrovascular diseases. Drugs targeting miR-135b for the treatment of diseases and related patents, highlighting the importance of this target and its utility as a therapeutic target for cardio-cerebrovascular diseases, have been discussed.

Ferroptosis is a newly discovered form of cell death that is influenced by iron levels and is triggered by cellular metabolism and excessive lipid peroxidation. Epigenetic regulation plays a crucial role in the development and progression of diseases, making it essential to understand these mechanisms in order to identify potential targets for drug development and clinical treatment. The intersection of ferroptosis and epigenetics has opened up new avenues for research in drug development, offering innovative strategies for combating diseases. Recent studies have shown that epigenetic modifications can impact pathways related to ferroptosis, potentially leading to organ dysfunction. Despite the increasing focus on this relationship, the role of epigenetic regulation in drug development remains largely unexplored. This article explores current research on the interplay between epigenetic regulation and ferroptosis, delving into their regulatory mechanisms and discussing the effects of existing epigenetic modification regulators on diseases. Additionally, we highlight ongoing research on epigenetic factors involved in targeting ferroptosis in cancer, providing new insights for the development of cancer treatments.

Glycans associated with biopharmaceutical drugs play crucial roles in drug safety and efficacy, and therefore, their reliable detection and quantification is essential. Our study introduces a multi-level quantification approach for glycosylation analysis in monoclonal antibodies (mAbs), focusing on minor abundant glycovariants. Mass spectrometric data is evaluated mainly employing open-source software tools. Released N-glycan and glycopeptide data form the basis for integrating information across different structural levels up to intact glycoproteins. Comprehensive comparison showed that indeed, variations across structural levels were observed especially for minor abundant species. Utilizing modification finder (MoFi), a tool for annotating mass spectra of intact proteins, we quantify isobaric glycosylation variants at the intact protein level. Our workflow's utility is demonstrated on NISTmAb, rituximab and adalimumab, profiling their minor abundant variants for the first time across diverse structural levels. This study enhances understanding and accessibility in glycosylation analysis, spotlighting minor abundant glycovariants in therapeutic antibodies.

Trastuzumab has improved survival rates in human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC), but drug resistance leads to treatment failure. Natural killer (NK) cell-mediated antibody-dependent cell cytotoxicity (ADCC) represents an essential antitumor immune mechanism of trastuzumab. Traditional Chinese medicine (TCM) has been used for centuries to treat diseases because of its capacity to improve immune responses. Xianling Lianxia formula (XLLXF), based on the principle of “strengthening body and eliminating toxin”, exhibits a synergistic effect in the trastuzumab treatment of patients with HER2-positive BC. Notably, this synergistic effect of XLLXF was executed by enhancing NK cells and ADCC, as demonstrated through in vitro co-culture of NK cells and BC cells and in vivo intervention experiments. Mechanistically, the augmented impact of XLLXF on NK cells is linked to a decrease in cytokine inducible Src homology 2 (SH2) containing protein (CISH) expression, which in turn activates the Janus kinase 1 (JAK1)/signal transducer and activator of transcription 5 (STAT5) pathway. Collectively, these findings suggested that XLLXF holds promise for enhancing NK cell function and sensitizing patients with HER2-positive BC to trastuzumab.

Tetrandrine (TET), a natural bisbenzyl isoquinoline alkaloid extracted from Stephania tetrandra S. Moore, has diverse pharmacological effects. However, its effects on melanoma remain unclear. Cellular proliferation assays, multi-omics analyses, and xenograft models were used to determine the effect of TET on melanoma. The direct target of TET was identified using biotin-TET pull-down liquid chromatograph-mass spectrometry (LC-MS), cellular thermal shift assays, and isothermal titration calorimetry (ITC) analysis. Our findings revealed that TET treatment induced robust cellular autophagy depending on activating transcription factor 6 (ATF6)-mediated endoplasmic reticulum (ER) stress. Simultaneously, it hindered autophagic flux by inducing cytoskeletal protein depolymerization in melanoma cells. TET treatment resulted in excessive accumulation of reactive oxygen species (ROS) and simultaneously triggered mitophagy. Sirtuin 5 (SIRT5) was ultimately found to be a direct target of TET. Mechanistically, TET led to the degradation of SIRT5 via the ubiquitin (Ub)-26S proteasome system. SIRT5 knockdown induced ROS accumulation, whereas SIRT5 overexpression attenuated the TET-induced ROS accumulation and autophagy. Importantly, TET exhibited anti-cancer effects in xenograft models depending on SIRT5 expression. This study highlights the potential of TET as an antimelanoma agent that targets SIRT5. These findings provide a promising avenue for the use of TET in melanoma treatment and underscore its potential as a therapeutic candidate.

Identifying the compound formulae-related xenobiotics in bio-samples is full of challenges. Conventional strategies always exhibit the insufficiencies in overall coverage, analytical efficiency, and degree of automation, and the results highly rely on the personal knowledge and experience. The goal of this work was to establish a software-aided approach, by integrating ultra-high performance liquid chromatography/ion-mobility quadrupole time-of-flight mass spectrometry (UHPLC/IM-QTOF-MS) and in-house high-definition MS² library, to enhance the identification of prototypes and metabolites of the compound formulae in vivo, taking Sishen formula (SSF) as a template. Seven different MS² acquisition methods were compared, which demonstrated the potency of a hybrid scan approach (namely high-definition data-independent/data-dependent acquisition (HDDIDDA)) in the identification precision, MS¹ coverage, and MS² spectra quality. The HDDIDDA data for 55 reference compounds, four component drugs, and SSF, together with the rat bio-samples (e.g., plasma, urine, feces, liver, and kidney), were acquired. Based on the UNIFI^TM platform (Waters), the efficient data processing workflows were established by combining mass defect filtering (MDF)-induced classification, diagnostic product ions (DPIs), and neutral loss filtering (NLF)-dominated structural confirmation. The high-definition MS² spectral libraries, dubbed in vitro-SSF and in vivo-SSF, were elaborated, enabling the efficient and automatic identification of SSF-associated xenobiotics in diverse rat bio-samples. Consequently, 118 prototypes and 206 metabolites of SSF were identified, with the identification rate reaching 80.51% and 79.61%, respectively. The metabolic pathways mainly involved the oxidation, reduction, hydrolysis, sulfation, methylation, demethylation, acetylation, glucuronidation, and the combined reactions. Conclusively, the proposed strategy can drive the identification of compound formulae-related xenobiotics in vivo in an intelligent manner.

The efficient immobilization of capture antibodies is crucial for timely pathogen detection during global pandemic outbreaks. Therefore, we proposed a silica-binding protein featuring core functional domains (cSP). It comprises a peptide with a silica-binding tag designed to adhere to silica surfaces and tandem protein G fragments (2C2) for effective antibody capture. This innovation facilitates precise site-directed immobilization of antibodies onto silica surfaces. We applied cSP to silica-coated optical fibers, creating a fiber-optic biolayer interferometer (FO-BLI) biosensor capable of monitoring the monkeypox virus (MPXV) protein A29L in spiked clinical samples to rapidly detect the MPXV. The cSP-based FO-BLI biosensor for MPXV demonstrated a limit of detection (LOD) of 0.62 ng/mL in buffer, comparable to the 0.52 ng/mL LOD achieved using a conventional streptavidin (SA)-based FO-BLI biosensor. Furthermore, it achieved LODs of 0.77 ng/mL in spiked serum and 0.80 ng/mL in spiked saliva, exhibiting no cross-reactivity with other viral antigens. The MPXV detection process was completed within 14 min. We further proposed a cSP-based multi-virus biosensor strategy capable of detecting various pandemic strains, such as MPXV, the latest coronavirus disease (COVID) variants, and influenza A protein, to extend its versatility. The proposed cSP-modified FO-BLI biosensor has a high potential for rapidly and accurately detecting MPXV antigens, making valuable contributions to epidemiological studies.

The overuse of antibiotics has led to the severe contamination of water bodies, posing a considerable hazard to human health. Therefore, the development of an accurate and rapid point-of-care testing (POCT) platform for the quantitative detection of antibiotics is necessary. In this study, Cerium oxide (CeO₂) and Ferrosoferric oxide (Fe₃O₄) nanoparticles were simultaneously encapsulated into N-doped nanofibrous carbon microspheres to form of a novel nanozyme (CeFe-NCMzyme) with a porous structure, high surface area, and N-doped carbon material properties, leading to a considerable enhancement of the peroxidase (POD)-like activity compared with that of the CeO₂ or Fe₃O₄ nanoparticles alone. The POD-like activity of CeFe-NCMzyme can be quenched using L-Cysteine (Cys) and subsequently restored by the addition of a quinolone antibiotic (norfloxacin, NOR). Therefore, CeFe-NCMzyme was used as a colorimetric sensor to detect NOR via an “On-Off” model of POD-like activity. The sensor possessed a wide linear range of 0.05-20.0 μM (R²= 0.9910) with a detection limit of 35.70 nM. Furthermore, a smartphone-assisted POCT platform with CeFe-NCMzyme was fabricated for quantitative detection of NOR based on RGB analysis. With the use of the POCT platform, a linear range of 0.1-20.0 μM and a detection limit of 54.10 nM were obtained. The spiked recoveries in the water samples were ranged from 97.73% to 102.01%, and the sensor exhibited good accuracy and acceptable reliability. This study provides a portable POCT platform for the on-site and quantitative monitoring of quinolone antibiotics in real samples, particularly in resource-constrained settings.

Alzheimer's disease (AD) is gradually increasing in prevalence and the complexity of its pathogenesis has led to a lengthy process of developing therapeutic drugs with limited success. Faced with this challenge, we proposed using a state-of-the-art drug screening algorithm to identify potential therapeutic compounds for AD from traditional Chinese medicine formulas with strong empirical support. We developed four deep neural network (DNN) models for AD drugs screening at the disease and target levels. The AD model was trained with compounds labeled for AD activity to predict active compounds at the disease level, while the acetylcholinesterase (AChE), monoamine oxidase-A (MAO-A), and 5-hydroxytryptamine 6 (5-HT₆) models were trained for specific AD targets. All four models performed excellently and were used to identify potential AD agents in the Kaixinsan (KXS) formula. High-scoring compounds underwent experimental validation at the enzyme, cellular, and animal levels. Compounds like 2,4-di-tert-butylphenol and elemicin showed significant binding and inhibitory effects on AChE and MAO-A. Additionally, 13 compounds, including α-asarone, penetrated the blood-brain barrier (BBB), indicating potential brain target binding, and eight compounds enhanced microglial β-amyloid phagocytosis, aiding in clearing AD pathological substances. Our results demonstrate the effectiveness of deep learning models in developing AD therapies and provide a strong platform for AD drug discovery.

Existing studies have shown that Astragalus membranaceus (AM) and its active ingredients astragalus polysaccharides, oninon, and astragalus methyl glycosides can attenuate X-ray radiation-induced injury. However, there are no studies on how isoliquiritigenin (ISL) attenuate the bystander effect of bone marrow mesenchymal stem cells (BMSCs) induced by carbon ion radiation therapy for lung cancer. This study aimed to investigate the AM-derived small molecule ISL to enhance radiotherapy sensitivity by attenuating the carbon ion radiation-induced bystander effect (RIBE) in BMSCs to elucidate its mechanism of action. In this study, we established a C57BL/6 mouse lung cancer transplantation tumor model in vivo and a co-culture model of A549 cells and BMSCs in vitro, and the models were successfully treated with carbon ions. In further work, we used flow cytometry, immunofluorescence, Western blot, enzyme-linked immunosorbent assay (ELISA), inhibitor, short hairpin RNA (shRNA), Cell Counting Kit-8 (CCK-8), and other methods to illustrate the mechanism. In the next experiments, we found that ISL combined with carbon ion radiotherapy had a significant anti-tumor effect and protected BMSCs from radiation damage. The aim of this study was to investigate the potential of ISL in enhancing the sensitivity of lung cancer cells to radiotherapy and attenuating RIBE in both in vitro and in vivo settings. Traditional Chinese medicine combined with radiation therapy is a promising and innovative treatment for non-small cell lung cancer. These results establish a theoretical foundation for further clinical development of ISL as a potential radiosensitizer option.