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ENVIRONMENTAL POLLUTION · 2023 · IF 8.9

Gaseous signaling molecule H2S as a multitasking signal molecule in ROS metabolism of Oryza sativa under thiocyanate (SCN−) pollution

Yu-Xi Feng,Peng Tian,Yu-Juan Lin,Dan-Yang Cao,Cheng-Zhi Li,Abid Ullah

The induction of disruption in the electronic transport chain by thiocyanate (SCN − ) leads to an excessive generation of reactive oxygen species (ROS) within rice ( Oryza sativa ). Hydrogen sulfide (H 2 S) assumes a crucial role as a gaseous signaling molecule, holding significant potential in alleviating SCN − -related stress. Nevertheless, there remains a dearth of understanding regarding the intricate interplay between H 2 S and ROS in Oryza sativa amidst SCN − pollution. In this investigation, a hydroponics-based experiment was meticulously devised to explore how H 2 S-mediated modifications influence the genetic feedback network governing ROS metabolism within the subcellular organelles of Oryza sativa when exposed to varying effective concentrations (EC 20 : 24 mg SCN/L; EC 50 : 96 mg SCN/L; EC 75 : 300 mg SCN/L) of SCN − . The findings unveiled the enhanced capacity of Oryza sativa to uptake SCN − under H 2 S + SCN − treatments in comparison to SCN − treatments alone. Notably, the relative growth rate (RGR) of seedlings subjected to H 2 S + SCN − exhibited a superior performance when contrasted with seedlings exposed solely to SCN − . Furthermore, the application of exogenous H 2 S yielded a significant reduction in ROS levels within Oryza sativa tissues during SCN − exposure. To elucidate the intricacies of gene regulation governing ROS metabolism at the mRNA level, the 52 targeted genes were categorized into four distinct types, namely: initial regulatory ROS generation genes (ROS-I), direct ROS scavenging genes (ROS-II), indirect ROS scavenging genes (ROS-III), and lipid oxidation genes (ROS-IV). On the whole, exogenous H 2 S exhibited the capacity to activate the majority of ROS-I ∼ ROS-IV genes within both Oryza sativa tissues at the EC 20 concentration of SCN − . However, genetic positive/negative feedback networks emphasized the pivotal role of ROS-II genes in governing ROS metabolism within Oryza sativa . Notably, these genes were predominantly activated within the cytoplasm, chloroplasts, mitochondria, peroxisomes, and the cell wall.

CAS / MDL: 333-20-0
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2023 · IF 8.2

Bisphenol A exposure exacerbates tracheal inflammatory injury in selenium-deficient chickens by regulating the miR-155/TRAF3/ROS pathway

Lin Peng,Shasha Chen,Hongjin Lin,Chunyan Wan,Xiang Li,Shiwen Xu,Shu Li

Bisphenol A (BPA) is an endocrine disruptor. Excessive BPA intake can damage the structure and function of the respiratory tract. Dietary selenium (Se) deficiency may also cause immune tissue damage. To investigate the potential mechanism of BPA on tracheal damage in selenium-deficient chickens and the role of microRNAs (miRNAs) in this process, we established in vitro and in vivo Se deficiency and BPA exposure models and screened out miR-155 for follow-up experiments. We further predicted and confirmed the targeting relationship between miR-155 and TRAF3 using TargetScan and dual luciferase assays and found that miR-155 was highly expressed and caused inflammatory damage. Further studies showed that BPA exposure increased airway oxidative stress, activated the NF-κB pathway, and caused inflammation and immune damage in selenium-deficient chickens, but down-regulating miR-155 and NAC treatment could reverse this phenomenon. This suggested that these pathways are regulated by the miR-155/TRAF3/ROS axis. In conclusion, BPA exposure aggravates airway inflammation in selenium-deficient chickens by regulating miR-155/TRAF3/ROS. This study revealed the mechanism of BPA exposure combined with Se deficiency in tracheal inflammatory injury in chickens and enriched the theoretical basis of BPA injury in poultry.

CAS / MDL: 80-05-7
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INTERNATIONAL JOURNAL OF PHARMACEUTICS · 2023 · IF 5.8

ROS/pH dual-sensitive emodin-chlorambucil co-loaded micelles enhance anti-tumor effect through combing oxidative damage and chemotherapy

Wendi Liang,Yingzhen Fan,Yinghui Liu,Ting Fang,Jian Zhang,Yuyi Xu,Ji Li,Dongkai Wang

The high level of reactive oxygen species (ROS) at the tumor site has been widely used in the tumor targeted delivery. However, the ROS stimulus-responsive vector itself is also a ROS consumer, and the consumption of endogenous ROS may not be sufficient to maintain sustained drug release. In this study, we designed and synthesized ROS/pH dual-sensitive polymer micelles for the co-delivery of emodin (EMD) and chlorambucil (CLB). The release of quinone methides (QM) can consume GSH, on the one hand, it can enhance the chemotoxicity of phenylbutyrate nitrogen mustard, on the other hand, emodin can induce oxidative damage of tumor cells and maintain the sustained targeted release of drugs.

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Nanoscale · 2023 · IF 6.7

Ultrasound-controllable ROS-responsive nanoplatform for O2 and NO generation to enhance sonodynamic therapy against multidrug-resistant bacterial infection

Yingyi Zhang,Lin Zhang,Yuhan Zhang,Rong Ju,Guoqing Wei

Antimicrobial sonodynamic therapy (SDT) has broad application potential in the eradication of multidrug-resistant (MDR) bacterial infections due to its non-invasiveness, absence of resistance concern, and high cytotoxicity. However, the hypoxic infection microenvironment and the rapid depletion of O2 during SDT severely limit the therapeutic efficacy of SDT. Herein, an ultrasound-controllable ROS-responsive nanoplatform (FOT/Fe3O4@Lipo-ICG) was constructed and prepared by encapsulating FOT and Fe3O4 nanoparticles (Fe3O4 NPs) within sonosensitiser ICG-modified liposomes. Both in vitro and in vivo, we observed that the ICG conjugation on the surface of liposomes could effectively maintain a good dispersion and prevent ICG aggregates in complex biological matrices. In addition, the liposomes could significantly block the catalytic activity of the Fe3O4 NPs, as well as the release of FOT, whereas upon US irradiation, the catalytic activity of Fe3O4 NPs was recovered to catalyse the decomposition of endogenous H2O2 into O2 and •OH. Meanwhile, the FOT was successfully released to react with endogenous glutathione to sequentially produce NO. Based on the aforementioned advantages, the FOT/Fe3O4@Lipo-ICG demonstrated potent efficacy in eradicating methicillin-resistant Staphylococcus aureus-induced local infection and sepsis resulting from local infection. Thus, the developed US-controllable nanoplatform offers a promising strategy for enhancing SDT for eradicating MDR bacterial infections.

CAS / MDL: 103-04-8
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AQUACULTURE · 2023 · IF 4.5

Quercetin dietary supplementation protects against difenoconazole-induced carp spleen inflammatory damage via regulating ROS/NF-κB/NLRP3 inflammasome axis

Enzhuang Pan,Huimiao Feng,Zuwang Yang,Yue Xin,Xiaomeng Ji,Kaixin Ping,Yong Sun,Jingquan Dong

As a widely used fungicide at present, difenoconazole can enter the aquatic ecosystem and cause adverse effects on freshwater carp culture. The spleen, an important immune organ of carp, is vulnerable to damage by environmental toxins. Studies have shown that the inflammatory response is an important mechanism of immunotoxicity of difenoconazole. Whereas quercetin has anti-inflammatory pharmacological activity, the role and mechanism of quercetin in difenoconazole-induced inflammatory damage in the spleen of carp is unknown. In this study, we developed a model for carp with quercetin added to the diet and exposed to environmentally relevant concentrations of difenoconazole. We found that quercetin protects against inflammatory damage in the splenic tissue of carp through histopathological observations. We found that quercetin alleviated ROS enrichment and disruption of redox homeostasis (dynamic balance of GSH, T-AOC, CAT, and MDA) in the spleen tissue of carp by fluorescence assay and biochemical assay. We found that quercetin was able to inhibit the activation of the NF-κB signaling pathway (elevated p-NF-κB p65 expression level) and NLRP3 inflammasome pathway (NLRP3/ASC/caspase-1) in carp spleen tissue induced by difenoconazole by immunohistochemistry and qPCR analysis. In conclusion, this study confirms that the addition of quercetin as a supplement to the diets of freshwater cultured carp is effective against the spleen toxicity induced by difenoconazole. Mechanistically, quercetin may alleviate the difenoconazole-induced splenic inflammatory injury in carp by suppressing the excessive activation of ROS/NF-κB/NLRP3 inflammasome axis, providing new insights into the mechanism of quercetin alleviation of splenic inflammatory injury in carp.

CAS / MDL: 119446-68-3
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COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY · 2023 · IF 3.9

Quercetin attenuates environmental Avermectin-induced ROS accumulation and alleviates gill damage in carp through activation of the Nrf2 pathway

Mengyuan Zhou,Jingchao Qiang,Jiajie Gan,Xuhui Xu,Xing Li,Shuai Zhang,Baoshi Xu,Zibo Dong

One of the most often used insecticides is Avermectin (AVM), which is toxic to aquatic organisms. Quercetin (Que) is a fruit and vegetable rich flavonoid with antioxidant activity. Fish gills are the most important respiratory organ. Carp is a biological model for studying environmental toxicology. To better understand the mechanism by which Que reduces AVM-induced gill damage in carp, we created a carp model with AVM and Que supplementation. In this study, four groups were created: the Control group, the Que group (400 mg/kg), the AVM group (2.404 μg/L), and the Que plus AVM group. The analytical methods used in this study were pathological structure examination, QPCR, Reactive Oxygen Species (ROS) and Western blot. The results showed that Que alleviated AVM-induced oxidative stress, inflammatory damage and apoptosis in the gill tissues of carp by activating the Nrf2 pathway. The mechanism was that Que alleviated the accumulation of ROS, reduced the balance between oxidation and antioxidant disrupted by AVM exposure, lowered the content of lipid peroxidation product malondialdehyde (MDA), and increased the content of antioxidant enzymes glutathione (GSH) and catalase (CAT). The Nrf2 pathway was activated. Meanwhile, Que inhibited apoptosis in the gills of carp by decreasing the levels of Bax, Cytochrome C(Cytoc), Caspase9, Cleaved-Caspase3, and elevating Bax. This is significant for future studies on Que and AVM. New recommendations are provided to reduce the threat of pollution in the water environment.

✓ 已验证 DOI PubMed 高影响因子
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CHEMICAL ENGINEERING JOURNAL · 2023 · IF 15.1

A ROS reservoir based on a polyoxometalate and metal-organic framework hybrid for efficient bacteria eradication and wound healing

Long Zhu,Antian Huo,Yanzhao Chen,Xue Bai,Chongjiang Cao,Yueqin Zheng,Weiwei Guo

Infections by bacteria always post significant challenges to global human health. Recent developed non-antibiotic treatment, such as using metal–organic frameworks (MOFs) to kill bacteria by generating reactive oxygen species (ROS) represents a promising strategy. However, drawbacks including low efficiencies of ROS generation and high concentrations of toxic metal ions released always exist. We have creatively designed a robust polyoxometalate (POM) and MOF hybrid (denoted as CuPOM-MOF@S) that functions as an efficient catalytic reservoir for cascaded generation of ROS (mainly ·OH) from H 2 O 2 thus eradicating bacteria and enhancing wound healing at an administration dosage as low as 5 μg∙mL −1 . The remarkable antibacterial capability surpasses those for most MOF-based materials reported thus far, which is mainly attributed to the reservation of massive catalytic copper ions, the synergistic effect regarding catalytic activity between MOFs and Keggin-type POMs as well as its bacteria-capturing ability by the coated surfactants. Its biological safety is investigated and confirmed by cell cytotoxicity and body weight assessment. This work presents a prospective strategy towards cascaded ROS generation by combining inorganic catalytic POMs with MOFs thus for multiple biomedical applications including treating bacterial infections and cancer as well as inducing biological signal responses.

CAS / MDL: 70-18-8 57-09-0 78-10-4
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Biomaterials Science · 2023 · IF 6.6

ROS-responsive Phenylboronic ester-based nanovesicles as multifunctional drug delivery systems for the treatment of inflammatory and thrombotic complications

Yu Xia,Runhai Chen,Ye Ke,Qiaoyi Han,Zhifang Ma,Qiang Shi

Inflammatory and thrombotic complications, and low loading of dual drugs with different hydrophilicity remain challenges to treat thrombosis with drug delivery systems (DDS). Here, the reactive oxygen species (ROS)-responsive amphiphilic block polymer poly(ethylene glycol)-b-2-((((4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl)oxy)carbonyl)oxy)ethyl methacrylate (PEG-b-PTBEM) is synthesized. And the nanovesicles (PPTV) are prepared successfully for the drug delivery platform by controlling the hydrophilic/hydrophobic ratio of molecular chains and molecular self-assembly. The anti-inflammatory drug indomethacin (IDM) is loaded in the wall of nanovesicels and the thrombolytic enzyme nattokinase (NK) is encapsulated in the aqueous cavity of nanovesicles. Both drugs can be rapidly released in the site of thrombus and/or inflammation with excessive ROS concentration. The dual drug-loaded nanovesicles not only eliminate ROS, but also alleviate inflammation and dissolve generated thrombus, showing significant therapeutic efficacy in the in-vivo mouse model of carrageenan tail thrombosis. Therefore, drug-delivery nanovesicles play multiple roles in the treatment of inflammation-induced thrombotic disorders, which offers a promising treatment for inflammatory and thrombotic complications.

✓ 已验证 产品关联 DOI PubMed 高影响因子
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EUROPEAN POLYMER JOURNAL · 2023 · IF 6

ROS-responsive core crosslinked micelles by combination of enzymatic polymerization and thiol-ene click chemistry for anticancer drug delivery

Pu Li,Qiang Liu,Zhenni Xiang,Jian Wang,Wan-Xia Wu,Wen-Jing Yi

The reactive oxygen species (ROS) responsive amphiphilic poly(ethylene glycol)- b -poly(thioketal) (mPEG- b -PTK) copolymer was synthesized by enzyme-catalyzed polymerization for the first time. Core crosslinked (CCL) micelles were prepared via thiol-ene click reaction between the double bond of the side chain of mPEG- b -PTK and the thiol group of pentaerythritol tetrakis (3-mercaptopropionate) as a crosslinker under UV light. The success of crosslinking was verified by NMR and IR. CCL micelles showed better stability in stability against dilution and storage stability experiments compared with the uncrosslinked (UCL) micelles. The ROS-responsiveness of CCL micelles was characterized by DLS, TEM, NMR, AFM and SEM. In vitro release studies, CCL micelles encapsulating doxorubicin (DOX) showed a faster release rate of nearly 100% within 32 h in PBS containing 5 mM H 2 O 2 compared to the control without H 2 O 2 . Cytotoxicity test demonstrated good biocompatibility of CCL micelles and low toxicity with cell viability above 82% and 86% in HeLa cells and HUVEC cells, respectively. And CCL DOX-loaded micelles exhibited great anticancer activity with IC 50 value about 4.8 mg/L for Hela cells. Finally, flow cytometry and confocal laser scanning microscope (CLSM) showed that DOX-loaded micelles had excellent internalization efficiency in HeLa cells. The obtained ROS-responsive CCL micelles held promise for anticancer drug delivery.

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CHEMICAL ENGINEERING JOURNAL · 2023 · IF 15.1

Platelet membrane-functionalized hollow mesoporous Prussian blue nanomedicine for comprehensive thrombolytic management by targeted enhanced fibrinolysis and ROS scavenging

Wenli Zhang,Maoyuan Sun,Yun Liu,Yu Zhang,Lian Xu,Ying Luo,Qianying Du,Jie Xu,Jia Liu,Jun Zhou,Haitao Ran,Zhigang Wang,Junrui Wang,Dajing Guo

Thrombotic diseases cause significant risks of disability and death worldwide. However, conventional thrombolytic drugs have short half-lives, poor targeting capabilities, limited therapeutic effects,   and narrow therapeutic windows. Moreover, most basic studies   focus only on thrombolytic efficiency and ignore the inflammatory factors that promote thrombosis progression, such as reactive oxygen species   (ROS)-mediated oxidative stress. Therefore, to achieve comprehensive and effective thrombolytic management, both targeted thrombolytic therapy and the elimination of inflammatory factors must be achieved. In this study, we developed a platelet membrane (PM)-functionalized hollow mesoporous Prussian blue nanomedicine (HMPB-rtPA@PM), which was innovatively coassembled from two FDA-approved drugs (Prussian blue (PB) and alteplase (rtPA)) and showed marked advantages in both thrombi targeting and photothermal/pharmacological synergistic fibrinolysis. Moreover, HMPB-rtPA@PM exhibited the potential to inhibit platelet aggregation and regulate the inflammatory microenvironment by scavenging ROS. As expected, this nanomedicine not only achieved more efficient thrombolysis in both thrombus models but also delayed thrombosis progression through therapeutic visualization in the black tail model. Such rational therapeutic principle provides a broad platform for the comprehensive management of thrombotic diseases.

CAS / MDL: 9000-07-1
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Small · 2023 · IF 13.3

Manganese-Based Immunomodulatory Nanocomposite with Catalase-Like Activity and Microwave-Enhanced ROS Elimination Ability for Efficient Rheumatoid Arthritis Therapy

Xiaotong Chen,Lianying Zhang,Haifeng Zeng,Wei Meng,Guijiang Liu,Wenhua Zhang,Pei Zhao,Qun Zhang,Ming Chen,Jinxiang Chen

Rheumatoid arthritis (RA) is a chronic autoimmune disease commonly associated with the accumulation of hyperactive immune cells (HICs), particularly macrophages of pro-inflammatory (M1) phenotype, accompanied by the elevated level of reactive oxygen species (ROS), decreased pH and O 2 content in joint synovium. In this work, an immunomodulatory nanosystem (IMN) is developed for RA therapy by modulating and restoring the function of HICs in inflamed tissues. Manganese tetraoxide nanoparticles (Mn 3 O 4 ) nanoparticles anchored on UiO-66-NH 2 are designed, and then the hybrid is coated with Mn-EGCG film, further wrapped with HA to obtain the final nanocomposite of UiO-66-NH 2 @Mn 3 O 4 /Mn-EGCG@HA (termed as UMnEH). When UMnEH diffuses to the inflammatory site of RA synovium, the stimulation of microwave (MW) irradiation and low pH trigger the slow dissociation of Mn-EGCG film. Then the endogenously overexpressed hydrogen peroxide (H 2 O 2 ) disintegrates the exposed Mn 3 O 4 NPs to promote ROS scavenging and O 2 generation. Assisted by MW irradiation, the elevated O 2 content in the RA microenvironment down-regulates the expression of hypoxia-inducible factor-1α (HIF-1α). Coupled with the clearance of ROS, it promotes the re-polarization of M1 phenotype macrophages into anti-inflammatory (M2) phenotype macrophages. Therefore, the multifunctional UMnEH nanoplatform, as the IMN, exhibits a promising potential to modulate and restore the function of HICs and has an exciting prospect in the treatment of RA.

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ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY · 2023 · IF 6.8

Manganese-induced apoptosis through the ROS-activated JNK/FOXO3a signaling pathway in CTX cells, a model of rat astrocytes

Wan-He Li,Zheng-Ting-Yan Xiang,An-Xin Lu,Su-Su Wang,Chong-Huai Yan

Manganese (Mn) is an essential trace element that maintains many normal physiological functions. However, multi-system disorders would occur once overexposure to Mn, especially neurotoxicity. Despite evidence demonstrating the critical role of ROS-activated JNK/FOXO3a signaling pathway in neuronal survival, the specific mechanisms by which it contributes to Mn-induced neurotoxicity are still unclear. The objectives of this study was to examine the modulation of the JNK/FOXO3a signaling pathway, which is activated by ROS, in Mn-induced apoptosis, using a rat brain astrocyte cell line (CTX cells). This study found that a dose-dependent decrease in cell viability of CTX cells was observed with 150, 200, 250, 300 μmol/L Mn. The results of apoptosis-related protein assay showed that Mn decreased the expression of anti-apoptotic protein Bcl-2 and enhanced the expression of apoptosis-related proteins like Bax and Cleaved-Caspase3. In addition, treatment with Mn resulted in elevated ROS levels and increased phosphorylation levels of JNK. Conversely, phosphorylation of nuclear transcription factors FOXO3a, which regulates expression of transcription factors including Bim and PUMA, was decreased. Depletion of ROS by N-acetyl- L -cysteine (NAC) and inhibition of the JNK pathway by SP600125 prevented Mn-induced JNK/FOXO3a pathway activation and, more importantly, the level of apoptosis was also significantly reduced. Confirmation of Mn-induced apoptosis in CTX cells through ROS generation and activation of the JNK/FOXO3a signaling pathway was the outcome of this study. These findings offer fresh insights into the neurotoxic mechanisms of Mn and therapeutic targets following Mn exposure.

CAS / MDL: 616-91-1 13446-34-9
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