INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2024
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IF 5.3
Jiaxin Li,Meng Li,Chengdong Zhang,Yachen Fei,Yuxiao Wang,Zhiqi Zhong,Chengjun Peng,Mengjie Li,Shuangying Gui,Jian Guo
Periodontitis is a multifactorial inflammatory disease characterized by severe alveolar bone damage and attachment loss. The imbalance of T help 17 (Th17) / regulatory T cells (Treg) induces excessive interleukin (IL)-17, which leads to alveolar bone damage and aggravates the development of periodontitis. Therefore, we proposed a therapeutic strategy to restore Th17/Treg homeostasis by interfering reactive oxygen species (ROS)-macrophage polarization cascade using active targeting microemulsions-based thermosensitive hydrogel. Folic acid-modified quercetin-loaded microemulsions (FA-Qu-MEs) were dispersed in poloxamer 407 and poly(N-isopropylacrylamide) matrix of hydrogel (FA-Qu-MEs@Gel). FA-Qu-MEs@Gel could be locally injected into the periodontal pocket and sustainedly release drugs. FA-Qu-MEs exhibited excellent ROS scavenging potency by targeting macrophages, resulting M1 phenotype macrophage from to M2 phenotype macrophage. Subsequently, the phenotypic changes of macrophages lead to decreased expression of IL-6 and tumor necrosis factor-α, which inhibited activated Th17, while IL-10 secreted by M2 macrophages promoted Treg differentiation. Finally, the restored Th17/Treg homeostasis reduced the level of IL-17 to accelerate alveolar bone regeneration. This study deigns a novel system that promote alveolar bone regeneration by remodeling Th17/Treg homeostasis via regulating ROS-macrophages polarization cascade for periodontitis treatment.
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Particle and Fibre Toxicology
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2024
·Vol. 21
·期 1
·1-19
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IF 7.2
Fan Junjie,Liu Li,Lu Yongling,Chen Qian,Fan Shijun,Yang Yongjun,Long Yupeng,Liu Xin
Background The global use of plastic materials has undergone rapid expansion, resulting in the substantial generation of degraded and synthetic microplastics and nanoplastics (MNPs), which have the potential to impose significant environmental burdens and cause harmful effects on living organisms. Despite this, the detrimental impacts of MNPs exposure towards host cells and tissues have not been thoroughly characterized. Results In the present study, we have elucidated a previously unidentified hepatotoxic effect of 20 nm synthetic polystyrene nanoparticles (PSNPs), rather than larger PS beads, by selectively inducing necroptosis in macrophages. Mechanistically, 20 nm PSNPs were rapidly internalized by macrophages and accumulated in the mitochondria, where they disrupted mitochondrial integrity, leading to heightened production of mitochondrial reactive oxygen species (mtROS). This elevated mtROS generation essentially triggered necroptosis in macrophages, resulting in enhanced crosstalk with hepatocytes, ultimately leading to hepatocyte damage. Additionally, it was demonstrated that PSNPs induced necroptosis and promoted acute liver injury in mice. This harmful effect was significantly mitigated by the administration of a necroptosis inhibitor or systemic depletion of macrophages prior to PSNPs injection. Conclusion Collectively, our study suggests a profound toxicity of environmental PSNP exposure by triggering macrophage necroptosis, which in turn induces hepatotoxicity via intercellular crosstalk between macrophages and hepatocytes in the hepatic microenvironment.
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BIOORGANIC CHEMISTRY
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2024
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IF 4.5
Yuchen Wang,Shi-Chao Lu,Hui Wen,Chunyue Zhao,Yanfei Jiang,Huaqing Cui
The limitations of commonly used sodium ascorbate-based catalyst system for copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction include excess production of reactive oxygen species and rapid catalyst deactivation. In this study instead of using a highly active reducing agent, such as, sodium ascorbate, we chose reducing sugar as a mild reducing agent to build up the catalyst system for CuAAC reaction. Interestingly, the bicinchoninic acid (BCA) assay system containing reducing sugar satisfies the essential elements of the catalyst system for CuAAC reaction. We found that CuSO 4 /BCA/Reducing sugar system can catalyze the CuAAC reaction but with low yield. Rational analyses of various parameters in CuSO 4 /BCA/Glucose catalyst system suggested storage at room temperature might enhance the catalytic activity, which was proven to be the case. Importantly, the system remains stable at room temperature and minimal H 2 O 2 was detected. Notably, our study showed that the coordination between the slow reduction of Cu(I) by reducing sugar and the selective chelation of Cu(I) by BCA is key to developing this system. The CuSO 4 /BCA/Reducing sugar catalyst system was successfully applied to various CuAAC reaction based bioanalyses, and it is suitable for the CuAAC reaction based bioanalyses that are sensitive to ROS or request long reaction time.
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LIFE SCIENCES
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2017
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IF 2.936
En-Xia Wang,Bo-Yang Zou,Lei Shi,Lin-Ying Du,Yan-Yan Zhu,Ya-Meng Jiang,Xiao-Dong Ma,Xiao-Hui Kang,Chang-Yuan Wang,Yu-Hong Zhen,Li-Dan Sun
Aims To investigate the antitumor effects of 7- O -geranylquercetin (GQ), a novel O -alkylated derivative of quercetin, against non-small cell lung cancer (NSCLC) cell lines A549 and NCI-H1975 and the corresponding mechanisms. Main methods Cell viability was assessed using MTT assay. The expression of proteins involved in apoptosis and autophagy was measured using western blotting. Besides, apoptosis was determined with DAPI staining, Annexin V-PI staining and transmission electron microscopy (TEM) assay, and autophagy was observed with TEM assay. Cell cycle and reactive oxygen species (ROS) level were detected using flow cytometry. Key findings GQ inhibited viability of A549 and NCI-H1975 cells in a dose- and time-dependent manner without apparent cytotoxicity to normal human lung fibroblast cells. GQ down-regulated the expression of apoptosis-related proteins pro-caspase 3 and Bcl-2, and up-regulated the expression of cleaved-PARP and Bax in A549 and NCI-H1975 cells. Meanwhile, GQ-induced cell apoptosis could be attenuated by caspase inhibitor Z-VAD-FMK. Besides, GQ induced autophagosome formation in A549 and NCI-H1975 cells, promoted the expression of autophagy-related proteins LC3-II and Beclin 1, and suppressed the expression of p62. Autophagy inhibition with chloroquine or Beclin 1 siRNA could effectively inhibit GQ-induced apoptosis. Furthermore, GQ treatment increased the generation of ROS, and ROS inhibitor N -acetylcysteine could reverse GQ-induced autophagy and apoptosis. Taken together, GQ could induce apoptosis and autophagy via ROS generation in A549 and NCI-H1975 cells, and GQ-induced autophagy contributed to apoptosis. Significance Our findings highlight that GQ is a promising anticancer agent for the treatment of lung cancer.
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Advanced Healthcare Materials
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2024
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IF 10
Saisai Ge,Xinyue Wang,Xinru Zhao,Lingling Yuan,Xuewei Bao,Caidie Sun,Zehua Gong,Jun Guo,Siyu Yuan,Danyou Hu,Jing Yang,Bin Yuan,Guiyang Zhang
Rheumatoid arthritis (RA) is a chronic immune disease characterized by the infiltration of immune cells and the proliferation of fibroblast-like synoviocytes (FLS) at the joint site, leading to inflammation and joint destruction. However, the available treatment options targeting both inflammatory and proliferative FLS are limited. Herein, this work presents three covalent organic frameworks (COFs) photothermal composite systems modified with multi-armed polyethylene glycols (PEG) for the treatment of RA. These systems exhibit a dual response under low pH and high reactive oxygen species (ROS) conditions at the site of inflammation, with a specific focus on delivering the protein drug ribonuclease A (RNase A). Notably, molecular docking studies reveal the interaction between RNase A and NF-κB p65 protein, and Western blotting confirm its inhibitory effect on NF-κB activity. In vitro and in vivo experiments verify the significant reduction in joint swelling and deformities in adjuvant-induced arthritis (AIA) rats after treatment with RNase A delivered by multi-armed PEG-modified COF ligands, restoring joint morphology to normal. These findings underscore the promising therapeutic potential of COFs for the treatment of RA, highlighting their unique capabilities in addressing both inflammatory and proliferative aspects of the disease and expanding the scope of biomedical applications for COFs.
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Advanced Therapeutics
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2024
·Vol. 7
·期 11
·2400275
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IF 3.7
Yao Yao,Binqing Xue,Duncan James Lessing,Weihua Chu
Alterations in the intestinal microenvironment, including increased levels of reactive oxygen species (ROS), abnormalities in intestinal mucosal immune regulation, and dysbiosis of the intestinal microbiota, are crucial to the development of inflammatory bowel disease (IBD). Herein, an oral colon-targeting Se-Probiotic@Alginate bead (BLSe) with ROS-scavenging ability and gut immune-microbiota microenvironment remodeling ability is developed using alginate as the primary outer shell encapsulated with probiotics Bacillus licheniformis (BL) and selenium nanoparticles stabilized by yeast glucan (SeNPs). In vitro studies have shown that SeNPs possess antioxidant activity and BLSe exhibits excellent stability in gastric fluids and are released in intestinal fluids. In vivo studies have also shown that BLSe significantly alleviated dextran sulphate sodium (DSS)-induced colitis in mice by inhibiting colon shortening, enhancing antioxidant activity, reducing pro-inflammatory cytokine secretion, and protecting the intestinal mucosal barrier. 16S ribosomal RNA sequencing shows that BLSe can remodel the composition of the gut microbiota by improving bacterial diversity and restoring the relative abundance of beneficial bacteria in the colon. Overall, this study advances a promising probiotic-based nanomedicine for managing IBD.
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Biomaterials Advances
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2025
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IF 6
Wajiha Ahmed,Shifen Li,Min Liang,Pai Peng,Wali Muhammad,Qiaoxuan Wang,Changyou Gao
Reactive oxygen species (ROS) and subsequent inflammatory cascades hinder the healing of diabetic wounds, which should be tackled simultaneously when designing wound dressings. In this study, ROS-responsive di‑selenium-containing polyurethane nanofibers (PUF) loaded with manganese dioxide nanoparticles (MnO 2 NPs) and gelsevirine (GSV) with an average diameter of 0.6 ± 10 μm, were prepared to specifically target ROS and inflammation control, thereby enhancing healing in diabetic wounds. The resulting nanofibers exhibited a porous architecture and enhanced drug delivery capability. The MnO 2 /GSV/PUF dressing showed negligible cytotoxicity with cell viability over 80 %, effective ROS-scavenging ability of 87 %, and inhibition of pro-inflammatory cytokine expression. This dual mechanism of ROS-scavenging and inflammation modulation accelerated the healing of diabetic wounds up to 92 % in 14 d in a full-thickness diabetic wound model, as evidenced by reduced cytokine levels, enhanced epithelialization, and uniform collagen deposition with the highest percentage of 60 %.
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CARBOHYDRATE POLYMERS
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2025
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IF 12.5
Qiuqun Xiao,Ruyi Peng,Tao Fang,Manzhen Zhou,Kailan Liu,Weihao Qiu,Yanshi Cen,Luyang Dai,Dongfang Zhou,Jun Wu,Yunrui Hu
Severe burn infections and impaired healing remain significant clinical challenges, with high mortality rates linked to immune microenvironment imbalances. While macrophages and reactive oxygen species (ROS) play crucial roles in inflammatory regulation, unilateral ROS modulation proves insufficient for optimal wound repair. This study develops an acid-responsive carboxymethyl chitosan-oxidized gellan gum-gentamicin sulfate (COGS) hydrogel that dynamically regulates the ROS-macrophage axis for enhanced burn treatment. Synthesized through oxidized gellan gum preparation and subsequent cross-linked with carboxymethyl chitosan/gentamicin sulfate via dynamic imine bonds and Ca 2+ -mediated ionic bridges, COGS demonstrates exceptional mechanical strength, self-healing capacity, and acid-responsive antibiotic release. In vitro evaluations reveal superior hemostatic performance and controlled drug release kinetics. In vivo studies demonstrate dual-phase therapeutic action: rapid gentamicin release eliminates pathogens during early infection while elevating ROS to activate M1 macrophages, followed by ROS reduction to promote M2 polarization during tissue regeneration. This dynamic immunomodulation balances inflammatory responses, accelerates tissue repair, and reduces gentamicin-related organ toxicity. By establishing temporal control over ROS levels and macrophage phenotypes, COGS hydrogel contributes to microenvironment remodeling for infectious burn healing. The COGS hydrogel synergistically addresses infection eradication and microenvironment remodeling through dynamic ROS-macrophage crosstalk regulation. This biomaterial-driven strategy advances precision immunotherapy paradigms for severe burn rehabilitation.
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Frontiers in Microbiology
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2025
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IF 4.5
Yongtian Yuan,Liangliang Zhao,Zhuchun Bei,Baogang Wang,Dongna Zhang,Likun Xu,Jiahui Liu,Meng Lv,Qin Xu,Yabin Song
Introduction: Drug-resistant bacteria, particularly Acinetobacter baumannii, present a significant threat to global public health, highlighting the urgent need for novel antibacterial therapies. Drug repurposing has emerged as a promising strategy to accelerate therapeutic development by identifying new applications for existing pharmaceuticals. This study investigates the potential of naphthoquine phosphate (NQP), an antimalarial agent, as a broad-spectrum antibacterial candidate against the multidrug-resistant strain A. baumannii LAC-4.Methods: To evaluate the antibacterial activity of NQP, we determined the minimum inhibitory concentration (MIC) against Acinetobacter baumannii LAC-4. Inhibition kinetics were analyzed to assess concentration-dependent effects. Membrane permeability assays were performed to examine NQP-induced changes in cell membrane integrity. Oxidative damage tests were conducted to investigate impacts on bacterial metabolic processes. Morphological changes in A. baumannii LAC-4 treated with NQP of MIC were observed using transmission electron microscopy (TEM) and scanning electron microscopy (SEM). Additionally, transcriptome analysis was performed to identify disrupted physiological pathways associated with NQP exposure.Results and discussion: NQP exhibited broad-spectrum antibacterial activity, with a MIC of 62.5 μg/mL against Acinetobacter baumannii LAC-4. Its inhibition kinetics curve confirmed a concentration-dependent inhibitory effect. Membrane permeability tests revealed that NQP disrupts cell membrane integrity, enhancing permeability—consistent with TEM/SEM observations showing significant structural damage in NQP-treated A. baumannii, including membrane rupture, cellular deformation, and cytoplasmic disorganization. Oxidative damage tests indicated NQP impacts bacterial metabolism, and transcriptome analysis further demonstrated that NQP disrupts multiple physiological pathways, primarily through enhanced membrane permeability and induced oxidative stress. These findings support NQP as a promising molecular scaffold for developing novel therapies against Acinetobacter baumannii infections, highlighting its potential in drug repurposing strategies for combating drug resistance.
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FREE RADICAL BIOLOGY AND MEDICINE
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2025
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IF 8.2
Liyun Zheng,Zhongwei Zhao,Li Chen,Wenjing Yang,Giorgio Ercolani,Pan Qin,Bin Lin,Mengzhu Han,Qiaoyou Weng,Yeyu Zhang,Bin Wu,Minjiang Chen,Zouying Yao,Shiji Fang,Jiansong Ji
Astragalin (ASG), a natural flavonoid glycoside, is known for its multiple pharmacological effects. In this study, we explored the antitumor effects of ASG and its underlying mechanism. Specifically, the growth inhibitory effects of ASG were assessed. Apoptosis rate, reactive oxygen species (ROS) accumulation, mitochondrial damage, and the activation of the endoplasmic reticulum stress induced by ASG were assessed. The potential target of ASG was identified and validated. The effects of ASG on immunogenic cell death (ICD) were determined. Furthermore, ASG’s growth inhibition was validated in vivo , and its potential synergistic effects with anti-PD-L1 antibody were examined. Our findings demonstrate that ASG effectively inhibits growth in liver cancer cell lines. ASG treatment induces apoptosis by promoting mitochondrial membrane potential disruption and ROS accumulation. Additionally, ASG directly bounds to quinone oxidoreductase 2 (NQO2), leading to a reduction in NQO2 protein levels and subsequent upregulation of key ER stress markers, including p-PERK, p-eIF2α, GRP78, and CHOP. Moreover, ASG induces hallmark features of ICD, including calreticulin exposure, nuclear high mobility group box 1 reduction, and adenosine triphosphate release. ASG-treated liver cancer cells effectively enhance dendritic cell maturation in a coculture system. In vivo , the tumor growth is synergistically inhibited by ASG combined with anti-PD-L1 antibody in Hepa1-6 tumor-bearing mice. This synergy is associated with increased dendritic cell maturation, enhanced CD8 + T cell infiltration, and a reduction in regulatory T cells. In conclusion, ASG can be served as a potential anticancer agent for liver cancer and enhance the antitumor efficacy of immunotherapy by activating the ROS-mediated endoplasmic reticulum stress and ICD pathways.
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Research
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2024
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IF 8.5
Hong Wei,Hongjun Huang,Haoqiang He,Yuanming Xiao,Lu Chun,Zhiqiang Jin,Hanyang Li,Li Zheng,Jinmin Zhao,Zainen Qin
The activation of pro-inflammatory M1-type macrophages by overexpression of reactive oxygen species (ROS) and reactive nitrogen species (RONS) in synovial membranes contributes to osteoarthritis (OA) progression and cartilage matrix degradation. Here, combing Pt and Se with potent catalytic activities, we developed a hybrid Pt–Se nanozymes as ROS and RONS scavengers to exert synergistic effects for OA therapy. As a result, Pt–Se nanozymes exhibited efficient scavenging effect on ROS and RONS levels, leading to repolarization of M1-type macrophages. Furthermore, the polarization of synovial macrophages to the M2 phenotype inhibited the expression of pro-inflammatory factors and salvaged mitochondrial function in arthritic chondrocytes. In vivo results also suggest that Pt–Se nanozymes effectively suppress the early progression of OA with an Osteoarthritis Research International Association score reduction of 68.21% and 82.66% for 4 and 8 weeks, respectively. In conclusion, this study provides a promising strategy to regulate inflammatory responses by macrophage repolarization processes for OA therapeutic.
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Food Chemistry-X
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2025
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IF 8.2
Lu Wang,Zhengrong Lin,Cheng Peng,Hua Zhang,Lulu Zhang,Shoujing Zheng,Jiebo Chen
Effects of red and blue light treatment on physiological quality, microbial loads, redox status and metabolomics profiles of fresh-cut sugarcane in vacuum and plastic packages were investigated during 15 d storage. The results showed that light synergistic vacuum treatment delayed the decrease of pH and the increase of respiration rate and microbial loads, enhanced antioxidant capacities and related enzymes activities. Light treatment was beneficial to 1 O 2 generation, but had opposite effects on O 2 − , H 2 O 2 and malondialdehyde. O 2− and H 2 O 2 was negatively associated with CAT, sucrose, fructose, glucose, 2-oxoglutaramate, liquiritigenin and dihydromyricetin, positively with PPO and malondialdehyde. Only phenylacetaldehyde exhibited a negative correlation with 1 O 2 . The biosynthesis of sugars, amino acids and flavonoids were the principal metabolite pathways corresponding to oxidative stress in fresh-cut sugarcane. It could be concluded that the concentration of ROS, especially O 2− and H 2 O 2 , should be appropriate to kill bacteria and retain the quality of fresh-cut sugarcane.
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