TALANTA
·
2025
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IF 6.1
Tiantian Chen,Qian Xiang,Xuemei Sang,Daxiu Li,Wenjiao zhou,Fengfeng Xu
Malaria remains a significant threat to global health, especially with the emergence of drug-resistant strains. Therefore, precise monitoring of antimalarial drug levels is crucial for assessing and managing drug resistance. Here, we report a multiplex aptasensor that enables simultaneous fluorescence detection of two antimalarial drugs (MQ and PQ) via split dsT7 promoter-mediated transcription of two-color light-up RNA aptamers. The detection mechanism relies on specific binding of target antimalarial drugs (MQ/PQ) to their aptamers, each triggering formation of intact dsT7 promoter to induce amplified transcription of its cognate RNA aptamer. The generated RNA aptamers bind their corresponding organic dyes (TO1-Biotin and MG) with high affinity, yielding 7.7-/25-fold fluorescence enhancement to enable ultrasensitive detection of MQ and PQ with limits of 0.71 ng/mL and 0.069 ng/mL, respectively. The method also exhibits high selectivity and low background signal. Furthermore, this label-free system achieves multiplexed detection of antimalarial drugs in 10-fold diluted human serum (recovery: 98.67–106.84 % for PQ and 99.89–106.19 % for MQ), demonstrating its real utility. This label-free system is adaptable to other biomarkers through aptamer replacement.
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高影响因子
MEDIATORS OF INFLAMMATION
·
2024
·
IF 4.4
Shuyu Ge,Zhenghong Guo,Ting Xiao,Pingping Sun,Bo Yang,Yin Ying
As an interstitial fibrosis disease characterized by diffuse alveolitis and structural alveolar disorders, idiopathic pulmonary fibrosis (IPF) has high lethality but lacks limited therapeutic drugs. A hospital preparation used for the treatment of viral pneumonia, Qingfei Tongluo mixture (QFTL), is rumored to have protective effects against inflammatory and respiratory disease. This study aims to confirm whether it has a therapeutic effect on bleomycin-induced IPF in rats and to elucidate its mechanism of action. Male SD rats were randomly divided into the following groups: control, model, CQ + QFTL (84 mg/kg chloroquine (CQ) + 3.64 g/kg QFTL), QFTL-L, M, H (3.64, 7.28, and 14.56 g/kg, respectively) and pirfenidone (PFD 420 mg/kg). After induction modeling and drug intervention, blood samples and lung tissue were collected for further detection. Body weight and lung coefficient were examined, combined with hematoxylin and eosin (H&E) and Masson staining to observe lung tissue lesions. The enzyme-linked immunosorbent assay (ELISA) and the hydroxyproline (HYP) assay kit were used to detect changes in proinflammatory factors (transforming growth factor-β (TGF-β), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β)) and HYP. Immunohistochemistry and Western blotting were performed to observe changes in proteins related to pulmonary fibrosis (α-smooth muscle actin (α-SMA) and matrix metalloproteinase 12 (MMP12)) and autophagy (P62 and mechanistic target of rapamycin (mTOR)). Treatment with QFTL significantly improved the adverse effects of bleomycin on body weight, lung coefficient, and pathological changes. Then, QFTL reduced bleomycin-induced increases in proinflammatory mediators and HYP. The expression changes of pulmonary fibrosis and autophagy marker proteins are attenuated by QFTL. Furthermore, the autophagy inhibitor CQ significantly reversed the downward trend in HYP levels and α-SMA protein expression, which QFTL improved in BLM-induced pulmonary fibrosis rats. In conclusion, QFTL could effectively attenuate bleomycin-induced inflammation and pulmonary fibrosis through mTOR-dependent autophagy in rats. Therefore, QFTL has the potential to be an alternative treatment for IPF in clinical practice.
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PHYTOMEDICINE
·
2025
·
IF 8.3
Guifang Fan,Xiaojiaoyang Li,Fanghong Li,Ranyun Chen,Xiaoyong Xue,Le Wang,Qi Zheng,Shuni Duan,Ranyi Luo,Rong Sun,Runping Liu
Background : Radix Bupleuri (RB) and acetaminophen (APAP) are two popular medications having potential hepatotoxicity and substantial risks of irrational co-administration and excessive use, posing an overlooked danger of drug-induced liver injury (DILI). Autophagy is a protective mechanism against APAP-induced DILI, yet, saikosaponin d (SSd) in RB has been characterized to regulate autophagy, although the current findings are controversial. Purpose : We aim to elucidate whether SSd promoted APAP-induced liver injury by regulating autophagy. Methods : UPLC-MS analysis was employed to measure the hepatic abundance of APAP-cysteine protein adducts. Multiple techniques such as fluorescence probe, proteinase K protection assay, immunoprecipitation-coupled proteomic analysis, surface plasmon resonance, molecular docking and et.al were applied to evaluate the SSd on autophagy flux. Results : We discovered that, by inhibiting autophagy, SSd impaired the removal of APAP-cysteine protein adducts and delayed the compensation of damaged mitochondria. This ultimately potentiated the development of severe liver toxicity induced by subtoxic APAP. The use of autophagy probes, transmission electron microscopy, membrane curative assay, and protein K assay collectively revealed that SSd predominately disrupted autophagosome-lysosome fusion, without affecting other stages of autophagic flux. Immunoprecipitation-coupled proteomic analysis and surface plasmon resonance further found that SSd directly bound to GABARAP, thus preventing the recruitment and autoactivation of STX17 and the following assembly of STX17-SNAP29-VAMP8 complex. Conclusion : In conclusion, our findings not only highlight the significant risk of drug-induced liver injury associated with the co-administration of RB and APAP in clinical practice but also unveils that GABARAP-SNARE complex is a novel druggable target for the treatment of autophagy-related diseases.
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Frontiers in Pharmacology
·
2024
·
IF 4.4
Abdelmoaty Ahmed Attia Ahmed,Chen Jing,Zhang Kun,Wu Changhui,Li Ye,Li Peng,Xu Jianhua
Background: Ganoderma lucidum (G. lucidum) is a famous medicinal mushroom that has been reported to prevent and treat a variety of diseases. Different extractions from G. lucidum have been used to manage age-related diseases, including cancer. Nevertheless, the senolytic activity of G. lucidum against senescent cancer cells has not been investigated. Although cellular senescence causes tumor growth inhibition, senescent cells promote the growth of the neighboring tumor cells through paracrine effects. Therefore, the elimination of senescent cells is a new strategy for cancer treatment.Methods: In this study, senescence was triggered in HCC cells by the chemotherapeutic agent Adriamycin (ADR), and subsequently, cells were treated with TC to assess its senolytic activity.Results: We found for the first time that the triterpenoid complex (TC) from G. lucidum had senolytic effect, which could selectively eliminate adriamycin (ADR)-induced senescent cells (SCs) of hepatocellular carcinoma (HCC) cells via caspase-dependent and mitochondrial pathways-mediated apoptosis and reduce the levels of senescence markers, thereby inhibiting the progression of cancers caused by SCs. TC could block autophagy at the late stage in SCs, resulting in a significant activation of TC-induced apoptosis. Furthermore, TC inhibited the senescence-associated secretory phenotype (SASP) in SCs through the inhibition of NF-κB, TFEB, P38, ERK, and mTOR signaling pathways and reducing the number of SCs. Sequential administration of ADR and TC in vivo significantly reduced tumor growth and reversed the toxicity of ADR.Conclusion: A triterpenoid complex isolated from G. lucidum may serve as a novel senolytic agent against SCs, and its combination with chemotherapeutic agents may enhance their antitumor efficacy.
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CHEMICO-BIOLOGICAL INTERACTIONS
·
2024
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IF 4.7
Jiaqi Li,Dezhi Chen,Jialiang Suo,Jiaqi Li,Yimu Zhang,Yu Wang,Zhewen Deng,Qi Zhang,Bo Ma
Triptolide (TP) is a major bioactive compound derived from Tripterygium wilfordii Hook . F . (TwHF) known for its medicinal properties, but it also exhibits potential toxic effects. It has been demonstrated to induce severe male reproductive toxicity, yet the precise mechanism behind this remains unclear, which limits its broad clinical application. This study aimed to investigate the mechanisms underlying testicular damage and spermatogenesis dysfunction induced by TP in mice, using both mouse models and the spermatocyte-derived cell line GC-2spd. In the present study, it was found that TP displayed significant testicular microstructure damaged and spermatogenesis defects including lower concentration and abnormal morphology by promoting ROS formation, MDA production and restraining GSH level, glutathione peroxidase 4 (GPX4) expression in vivo . Furthermore, Ferrostatin-1 (FER-1), a ferroptosis inhibitor, was found to significantly reduce the accumulation of lipid peroxidation, alleviate testicular microstructural damage, and enhance spermatogenic function in mice. Besides, notably decreased cell viability, collapsed mitochondrial membrane potential, and elevated DNA damage were observed in vitro . The above-mentioned phenomenon could be reversed by pre-treatment of FER-1, indicating that ferroptosis participated in the TP-mediated spermatogenesis dysfunction. Mechanistically, TP could enhance GPX4 ubiquitin degradation via triggering K63-linked polyubiquitination of GPX4, thereby stimulating ferroptosis in spermatocytes. Functionally, GPX4 deletion intensified ferroptosis and exacerbated DNA damage in GC-2 cells, while GPX4 overexpression mitigated ferroptosis induced by TP. Overall, these findings for the first time indicated a vital role of ferroptosis in TP induced-testicular injury and spermatogenic dysfunction through promoting GPX4 K63-linked polyubiquitination, which hopefully offers a potential therapeutic avenue for TP-related male reproductive damage. In addition, this study also provides a theoretical foundation for the improved clinical application of TP or TwHF in the future.
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Frontiers in Immunology
·
2025
·
IF 5.9
Huimin Xie,Lin Ma,Xiaoli He,Songsong Zhao,Jin Wang,Ao Zhu,Changming Liu,Olga Piskareva,Chao Deng,Fenghua Meng,Mi Liu
Introduction: Cancer vaccines work through activating tumor-specific T cells, which can specifically attack cancer cells by recognizing antigens binding with Major-Histocompatibility-Complex I (MHC I) molecules. The downregulation or loss of MHC I expression on tumor cells can affect the efficacy of cancer vaccines.Methods: Herein, to increase the MHC I expression on tumor cells, a nanovesicle-based strategy was developed to improve the efficacy of cancer vaccines. Several clinically applied medicines, such as tyrosine kinase inhibitors (TKIs), were screened for their capacity to upregulate MHC I.Results: Two TKIs, Sunitinib and Sorafenib, were found to be very effective in elevating MHC I expression, and they were encapsulated into redox-responsive nanovesicles respectively (SUN-KD10 or SOR-KD10), which demonstrated favourable tumor-targeting capabilities in the tumor microenvironment. Sunitinib or Sorafenib activates the IFNγ/STAT1 pathway, which improve the expression of MHC I. When combined with whole-tumor-antigen-loaded nanovaccines, these nanovesicle formulations elicited a synergistic antitumor effect in both breast cancer and melanoma mouse models. The tumors in the tumor-bearing mice treated with combined strategy grew more slowly and the survival times of such mice are significantly prolonged.Discussion: The studies demonstrated that more tumor-specific T cells were activated in the combined strategy treated mice, suggesting improved immune-mediated tumor clearance. This combinatorial approach provides a promising strategy to overcome immune evasion and to enhance the therapeutic outcomes of cancer vaccine-based immunotherapy by using clinical-applied medicines with cancer vaccines.
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