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BIOLOGICAL & PHARMACEUTICAL BULLETIN · 2023 ·Vol. 46 ·期 1 ·26-34 · IF 2

IFI6 Downregulation Reverses Oxaliplatin Resistance of Colorectal Cancer Cells by Activating the ROS-Induced p38MAPK Signaling Pathway

Chen Huang,Tao Zhou,Lihua Ma,Shipeng Zhao

Oxaliplatin (OXA) is a usual chemotherapeutic agent applied in the colorectal cancer (CRC) clinical treatment. Interferon-alpha inducible protein 6 (IFI6) has been proved to promote proliferation and suppress apoptosis in several tumor cells, while the impacts of IFI6 on OXA resistance in CRC still need exploration. HCT116 and SW620 cells were used as the parental to obtain OXA-resistant cells. The influence of IFI6 on OXA sensitivity, cell proliferation and apoptosis were evaluated by overexpression or knockdown IFI6 in cells. In this work, we found that the level of IFI6 was significantly enhanced in HCT116/OXA and SW620/OXA cells as compared to the parental cells. Overexpression of IFI6 decreased the sensitivity of HCT116 and SW620 cells to OXA. However, knockdown of IFI6 enhanced the sensitivity of HCT116/OXA and SW620/OXA cells to OXA. And upregulated IFI6 promoted the proliferation and repressed apoptosis in HCT116 cells, while suppressed IFI6 markedly reduced proliferation and increased apoptosis in HCT116/OXA cells. Additionally, IFI6 suppressed the phosphorylation level of p38, and silenced IFI6 enhanced it. The addition of the p38 kinase inhibitor, SB203580, alleviated the decreased cell proliferation and increased apoptosis in HCT116/OXA cells. Suppressed IFI6 enhanced the reactive oxygen species (ROS) level in HCT116/OXA cells, and blockade of ROS with N-acetyl-L-cysteine (NAC) decreased the enhancement level of ROS and the phosphorylation level of the p38, which was induced by IFI6 down-regulation. We, therefore, implied that suppressed IFI6 reverses OXA-resistance of CRC cells via promoting the ROS-induced p38 mitogen-activated protein kinase (MAPK) signaling pathway.

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ACS Applied Energy Materials · 2022 · IF 6.959

Oxygen Vacancy Defect Engineering of Heterophase Junction TiO2: Interfacial/Surface Oxygen Vacancies Coadjust the Photocatalytic ROS Production

Xiaoshuang Kang,Guohui Dong,Tingting Dong

In this study, TiO2 samples are synthesized through two stages including hydrolysis and calcination. It is found that the addition of HCl in the hydrolysis stage could facilitate the formation of heterophase junction TiO2. By annealing at 300 °C in an argon atmosphere, interfacial oxygen vacancies (Vo) and surface Vo (distributed in the anatase phase) can be constructed in the heterophase junction TiO2. After photocatalytic experiments, it can be found that surface Vo and interface Vo have a synergistic effect in the production of photocatalytic reactive oxygen species (ROSs). Surface Vo can enrich O2 and transmit electrons to O2 on the surface of anatase. Therefore, the enriched O2 can be converted into •O2– and 1O2 easily. The interfacial Vo not only facilitate the electron transmission between the two phases but also change the electron transfer mode from I-scheme to Z-scheme. Thus, interfacial Vo make photogenerated electrons transfer to anatase and photogenerated holes leave in the rutile. These holes in the rutile part have high oxidation potential and can better oxidize H2O (or OH–) molecules to •OH. They can also oxidize •O2– to 1O2. This work promotes the further development of defect design and application in photocatalytic materials.

CAS / MDL: 3317-61-1 10602-37-6
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BIOMACROMOLECULES · 2019 · IF 5.667

Reactive Oxygen Species (ROS)-Degradable Polymeric Nanoplatform for Hypoxia-Targeted Gene Delivery: Unpacking DNA and Reducing Toxicity

Yuxin Zhang,Jie Zhou,Shengnan Ma,Yiyan He,Jun Yang,Zhongwei Gu

Smart polymers as ideal gene carriers have drawn increasing attentions due to the effective DNA release once triggered by intrinsic stimuli, as well as reduced cytotoxicity. Herein, a stimulus-responsive, positively charged and water-soluble polymer (OEI-TKx) was facilely engineered by cross-linking low molecular weight oligoethylenimine (OEI) via thioketal (TK) linkages that would cleave selectively in reactive oxygen species (ROS)-rich environments induced by hypoxia. Agarose gel electrophoresis assay demonstrated that the threshold N/P ratios for complete retardation of negatively charged DNA migration were above 5 for OEI-TKx. The reduction in DNA-condensing capability and the changes in particle size, size distribution and particle morphology all illustrated that OEI-TKx possessed excellent ROS responsiveness. OEI-TKx/DNA polyplexes showed lower toxicity and higher gene transfection efficiency compared with PEI/DNA polyplexes. The optimum formulation, OEI-TKx/DNA polyplexes (N/P = 40), showed a little better performance than PEI/DNA polyplexes in cellular uptake profile. Furthermore, OEI-TKx/DNA polyplexes could escape from endosomes to the cytosol as efficiently as PEI/DNA polyplexes. Confocal images confirmed that OEI-TKx/DNA polyplexes could more effectively release DNA than PEI/DNA polyplexes, mainly owing to the valid cleavage of thioketal linkages induced by characteristic rich-ROS in Hela cells. These results suggested that OEI-TKx could represent an on-demand stimulus-responsive gene delivery platform.

CAS / MDL: 107-96-0
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FOOD CHEMISTRY · 2018 · IF 4.946

Sodium para-aminosalicylate delays pericarp browning of litchi fruit by inhibiting ROS-mediated senescence during postharvest storage

Taotao Li,Dingding Shi,Qixian Wu,Zhengke Zhang,Hongxia Qu,Yueming Jiang

The effect of sodium para -aminosalicylate (PAS-Na) on litchi pericarp browning and the potential regulating mechanism was investigated in this study. Results showed that 0.3 g L −1 PAS-Na significantly inhibited the development of pericarp browning and reduced respiration rate of litchi fruit. PAS-Na inhibited the production of reactive oxygen species (ROS) and decreased the expression level of senescence-related genes. Additionally, PAS-Na treatment enhanced the activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX), which might contribute to the scavenging of ROS. Meanwhile, PAS-Na treatment maintained membrane integrity as indicated by reduced relative membrane leakage rate and malondialdehyde (MDA) content, as well as lower activities of membrane lipids-degrading enzymes: lipase and lipoxygenase (LOX). Amino acids, especially GABA, Glu, Met contents were also significantly affected by PAS-Na treatment. Taken together, we postulated that PAS-Na treatment might be a promising method for controlling postharvest browning and prolonging shelf-life of harvested litchi fruit.

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JOURNAL OF RARE EARTHS · 2019 · IF 2.846

Lanthanum elicitation on hypocrellin A production in mycelium cultures of Shiraia bambusicola is mediated by ROS generation

Cansong Lu,Yanjun Ma,Jianwen Wang

Rare earth elements (REEs) have been widely applied as efficient elicitors to improve production of biologically important secondary metabolites in plants. However, their effects on microbial secondary metabolites were seldom reported. In this study, lanthanum (LaCl 3 ) was used as an elicitor in mycelium cultures of Shiraia bambusicola to stimulate the production of hypocrellin A (HA), a promising photosensitizer for anticancer photodynamic therapy. La 3+ at 1.0 g/L not only increases HA content by 2.50-fold in mycelia, but stimulates HA exudation to the medium with the highest production (225.05 mg/L) on day 6. Further analysis shows that La 3+ can induce the intracellular ROS (reactive oxygen species) accumulation with 2.33-fold higher contents of H 2 O 2 in mycelium. HA production induced by La 3+ treatment can be suppressed by ROS scavengers. Further analysis reveals that the elicitation of La 3+ on HA accumulation is mediated by ROS generation to enhance expression of HA biosynthetical genes. The expression of ATP-binding cassette transporter gene ( SbABC ) for HA exudation is also regulated partially via ROS generated by NADPH oxidase . These results indicate that the enhanced HA production by La 3+ might be mediated by ROS signaling pathway. Our results provide a basis for understanding REE elicitation on fungal metabolites and a practical biotechnological process for enhanced production of HA.

CAS / MDL: 10025-84-0
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CARBOHYDRATE POLYMERS · 2018 · IF 5.158

Light controllable chitosan micelles with ROS generation and essential oil release for the treatment of bacterial biofilm

Zhaojie Wang,Hu Bai,Chunbo Lu,Chunyan Hou,Yuanhao Qiu,Peng Zhang,Jinyou Duan,Haibo Mu

Bacterial biofilms are widely associated with persistent infections and food contamination. High resistance to conventional antimicrobial agents resulted in an urgent need for novel formulation to eliminate these bacterial communities. Herein we fabricated light controllable chitosan micelles loading with thymol (T-TCP) for elimination of biofilm. Due to the exterior chitosan, T-TCP micelles easily bind to negative biofilm through electrostatic interaction and efficiently deliver the essential oil payloads. Under irradiation, T-TCP micelles generated ROS , which triggered simultaneous thymol release and also resulted in additional ROS-inducing bactericidal effects, both effectively eradicating biofilms of Listeria monocytogenes and Staphylococcus aureus . This formulation provided a platform for other water-insoluble antimicrobials and might be used as a potent and controllable solution to biofilm fighting.

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Small · 2018 ·Vol. 14 ·期 38 ·1802337 · IF 9.598

Photosensitizer and Autophagy Promoter Coloaded ROS-Responsive Dendrimer-Assembled Carrier for Synergistic Enhancement of Tumor Growth Suppression

Ting Wang,Jinhui Hu,Hao Luo,Huiyang Li,Jiahong Zhou,Lin Zhou,Shaohua Wei

Reactive oxygen species (ROS) generated during photodynamic therapy (PDT) can trigger autophagy. However, little research is focused on whether there is a synergistic anticancer effect with PDT if extra autophagy promoter or inhibitor is added. Here, it is found that autophagy promotion significantly enhances the PDT activity to cancer cells. Based on this preliminary result, a ROS-sensitive self-assembled dendrimer nanoparticle is exploited as a carrier to codeliver an autophagy promoter (rapamycin, Rapa) and photosensitizer (phthalocyanine, Pc) to the tumor. After entrapped by cancer cells and irradiated by light, the ROS generated in PDT process of Pc can trigger nanoparticle destruction to release Rapa, thus initiating the autophagy process and remarkably enhancing the efficacy of PDT, leading to efficient tumor suppression.

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APPLIED MICROBIOLOGY AND BIOTECHNOLOGY · 2018 ·Vol. 102 ·期 15 ·6659-6672 · IF 3.34

Nerol-induced apoptosis associated with the generation of ROS and Ca2+ overload in saprotrophic fungus Aspergillus flavus

Tian Jun,Gan Yeyun,Pan Chao,Zhang Man,Wang Xueyan,Tang Xudong,Peng Xue

The contamination of food with Aspergillus flavus and subsequent aflatoxins is one of the most serious safety problems in the world. In this study of nerol (NEL)’s antifungal mechanism of action, we observed morphological and physiological changes in Aspergillus flavus. We found that NEL resulted in elevated levels of reactive oxygen species (ROS) and calcium ions (Ca 2+ ). On ROS assays, compared with the controls, the proportion of fluorescent cells treated with concentrations of 0.25, 0.5, 1, and 2 μL/mL NEL increased to 8.4 ± 1.07%, 10.2 ± 1.72%, 13.4 ± 0.50%, and 26.2 ± 4.21%, respectively. Increased mitochondrial dysfunction and oxidative stress induced by the interactions between Ca 2+ and ROS subsequently activate the release of cytochrome c and caspase activity. Characteristic changes of apoptosis were also observed via various detection methods, including phosphatidylserine externalization, nuclear condensation, and DNA fragmentation. Meanwhile, we found that the expression of CaMKs increased significantly in NEL-treated cells. In conclusion, our findings indicate that NEL has great potential as an eco-friendly antifungal agent for food preservation.

CAS / MDL: 106-25-2
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SOLAR ENERGY · 2018 · IF 4.374

Preparation of meso-Ag/Al2O3 and synergistic water disinfection of metallic silver and ROS under visible light

Huajun Chen,Wenjie Tian,Wuxiu Ding

Metallic sliver-doped mesoporous Al 2 O 3 fibers (meso-Ag/Al 2 O 3 ) that can harvest visible light to speed up solar water purification, were synthesized by one-pot hydrothermal method. Insightful analyses of XRD, XRF and XPS of meso-Ag/ Al 2 O 3 verified that metallic silver occupied interstitial positions of Al 2 O 3 lattice forming interstitial solid solution. N 2 adsorption/desorption illustrated that meso-Ag/Al 2 O 3 exhibited significantly increases in the specific surface area, pore volume and average pore diameter after doping with silver. The UV–Vis diffuse reflectance spectra and disinfection performance indicated that meso-Ag/Al 2 O 3 can harvest visible light to promote the conversion of dioxygen to ROS for water disinfection compared with the widely used TiO 2 . With our approach, we achieved water disinfection of >99.999% inactivation of bacteria in 120 min with a small amount of material (8 mg/L) under simulated visible light.

CAS / MDL: 7761-88-8
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BIOSCIENCE REPORTS · 2019 ·Vol. 39 ·期 6 · IF 2.535

S-ethyl ethanethiosulfinate, a derivative of allicin, induces metacaspase-dependent apoptosis through ROS generation in Penicillium chrysogenum

Qi Feilong,Zhang Chen,Jiang Shanshan,Wang Qian,Kuerban Kudelaidi,Luo Man,Dong Mengxue,Zhou Xinguang,Wu Laiming,Jiang Biao,Ye Li

Allicin can be used as fumigant to protect food and cultural relics from fungal contamination because of its strong antifungal activity and the characteristics of high volatility and no residues. However, the obvious disadvantages such as high minimal inhibitory concentration and instability prevent it from wide application. In this study, a stable derivative of allicin, S-ethyl ethanethiosulfinate (ALE), was synthesized. We further explored its antifungal activity and apoptosis-inducing effect, as well as the underlying mechanism. ALE had an excellent capability of inhibiting spore germination and mycelial growth of Penicillium chrysogenum observed by inverted microscope and scanning electron microscopy. XTT colorimetric assay indicated ALE could reduce the cell viability obviously and IC50 was 0.92 μg/ml, only 1/42 of allicin (38.68 μg/ml). DHR 123 ROS Assay Kit, flow cytometry assay and confocal immunofluorescence revealed intercellular ROS generation and metacaspase-dependent apoptosis triggered by ALE, while antioxidant tocopherol could reverse ALE-induced cytotoxicity effect and metacaspase activation. These results indicate that ALE induces metacaspase-dependent apoptosis through ROS generation, thus possesses an effective antifungal activity. This new derivative of allicin might be developed as a high efficient alternative to the conventional fungicides for food storage and cultural relic protection.

CAS / MDL: 298-93-1
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ADVANCED FUNCTIONAL MATERIALS · 2019 ·Vol. 29 ·期 36 ·1904056 · IF 15.621

Fe(III)-Porphyrin Sonotheranostics: A Green Triple-Regulated ROS Generation Nanoplatform for Enhanced Cancer Imaging and Therapy

Jing Zhu,Chengchao Chu,Dongsheng Li,Xin Pang,Huili Zheng,Junqing Wang,Yesi Shi,Yang Zhang,Yi Cheng,En Ren,Jingliang Cheng,Xiaoyuan Chen,Gang Liu

To address the urgent need for effective sonodynamic therapy (SDT), a facile and efficient strategy is developed for fabricating a new class of sonotheranostics. Herein, a Fe(III)-porphyrin nano-sonosensitizer is prepared by a one-step coordination synthesis, and then anchored with Bis(DPA-Zn)-RGD and manganese superoxide dismutase (SOD2) siRNA. Benefiting from the delicate interactions of the Fe(III)-coordinated nanoformulations, a highly potent sono/gene combinational therapy guided by fluorescence/magnetic resonance imaging is achieved. Importantly, this sonotheranostics significantly enhances the SDT effect of porphyrin through the cancer-targeted delivery capability and enhanced reactive oxygen species production via triple-regulated approaches, including down-regulation of SOD2, depletion of glutathione, and generation of Fenton reaction. This work opens up new perspectives for developing versatile sonotheranostics to overcome the clinical challenges of SDT.

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Theranostics · 2024 · IF 12.4

An injectable magnesium-loaded hydrogel releases hydrogen to promote osteoporotic bone repair via ROS scavenging and immunomodulation

Hang Zhou,Zhongyuan He,Youde Cao,Lei Chu,Bing Liang,Kexiao Yu,Zhongliang Deng

Background: The repair of osteoporotic bone defects remains challenging due to excessive reactive oxygen species (ROS), persistent inflammation, and an imbalance between osteogenesis and osteoclastogenesis. Methods: Here, an injectable H 2 -releasing hydrogel (magnesium@polyethylene glycol-poly(lactic-co-glycolic acid), Mg@PEG-PLGA) was developed to remodel the challenging bone environment and accelerate the repair of osteoporotic bone defects. Results: This Mg@PEG-PLGA gel shows excellent injectability, shape adaptability, and phase-transition ability, can fill irregular bone defect areas via minimally invasive injection, and can transform into a porous scaffold in situ to provide mechanical support. With the appropriate release of H 2 and magnesium ions, the 2Mg@PEG-PLGA gel (loaded with 2 mg of Mg) displayed significant immunomodulatory effects through reducing intracellular ROS, guiding macrophage polarization toward the M2 phenotype, and inhibiting the IκB/NF-κB signaling pathway. Moreover, in vitro experiments showed that the 2Mg@PEG-PLGA gel inhibited osteoclastogenesis while promoting osteogenesis. Most notably, in animal experiments, the 2Mg@PEG-PLGA gel significantly promoted the repair of osteoporotic bone defects in vivo by scavenging ROS and inhibiting inflammation and osteoclastogenesis. Conclusions: Overall, our study provides critical insight into the design and development of H 2 -releasing magnesium-based hydrogels as potential implants for repairing osteoporotic bone defects.

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