BIOLOGICAL & PHARMACEUTICAL BULLETIN
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2023
·Vol. 46
·期 1
·26-34
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IF 2
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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Materials Today Bio
·
2023
·
IF 8.2
Fangying Yu,Xuwei Shang,Zixu Wang,Yun Zhu,Simin Chen,Hong Yuan,Fuqiang Hu
Ferroptosis as promising antitumor therapy strategy could be comprised by intracellular antioxidants, especially GSH and thioredoxin (Trx). They are both cofactors of Gpx4, the enzyme catalyzing the production of lipid peroxides to relieve oxidative stress, which drives the acquired ferroptosis resistance in tumors. Herein, the NADPH-consuming micelles are specially designed, which could collaborate with the ROS generating photodynamics therapy (PDT) by depleting intracellular GSH and Trx under hypoxia condition, resulting in ruined redox homeostasis and the final cascade amplified ferroptosis. The tailored micelle was briefly prepared by conjugating hypoxia-sensitive segment p-nitrobenzyl chloroformate (PNZ-Cl) to the hydrophilic chitosan (CS), the resulting micelle was further modified with photosensitizer Ce6 via PEG linkage. When receiving laser irradiation, the photosensitizer would generate ROS and consume oxygen in the meanwhile. The resulting anabatic hypoxia in turns promote the NTR-catalyzed electron-accepting response of micelles, with evidently enhanced NADPH consumption and ultimately ruined redox homeostasis, contributing to cascade amplified ferroptosis with robust ROS. Most importantly, the accompanied immunogenic cell death (ICD) and releasing danger-associated molecular patterns (DAMPs) could boost dendritic cells (DCs) maturation and the subsequent T-cell-mediated profound immune response. Collectively, the work excavates the other biochemical reaction during the hypoxia-sensitive process of C–N–Ce6 by diminishing intracellular GSH and Trx, providing a candidate of ferroptosis inducers against solid tumors.
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ACS Applied Energy Materials
·
2022
·
IF 6.959
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.
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PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY
·
2023
·
IF 4.7
Naixi Yang,Jinming Guo,Hao Wu,Meichen Gao,Shiwen Xu
Chlorpyrifos (Diethoxy-sulfanylidene-(3,5,6-trichloropyridin-2-yl) oxy-λ 5 -phosphane, CPF) was extensively used organophosphorus pesticide , extensively deteriorating public problem with the enrichment in the water bodies. Eucalyptol (1,3,3-Trimethyl-2-oxabicyclo[2.2.2] octane, EUC), a colorless cyclic monoterpene oxide, has shown anti-inflammatory and anti-oxidation properties. To explore the effect of EUC on CPF-induced necroptosis in the grass carp liver cells (L8824 cells), we treated L8824 cells with 60 mM CPF and 5 μM EUC for 24 h. The results showed that CPF exposed lead to excessive accumulation of reactive oxygen species (ROS) and oxidative stress , activating the NF-κB and RIPK1 pathway, increasing the level of cell necroptosis. However, EUC treatment attenuated the toxic effects of CPF treatment on L8824 cells. In summary, the study demonstrated that CPF induced necroptosis and inflammation, and EUC treatment could decrease CPF-caused cell injury.
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MATERIALS & DESIGN
·
2023
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IF 8.4
Mingqiao Li,Hedan Xu,Nan Zhao,Liangjun Zhang,Haihan Xia,Xiaoxun Zhang,Qiao Li,Min Liao,Qiong Pan,Zeng Yi,Jin Chai
Acute liver injury (ALI) is one of the most important causes of liver failure, and there are no FDA-approved drugs that could therapy late-stage ALI. It has been shown in this study that HA-PEI, a molecule formed by covalently combining HA and PEI, can effectively treat advanced ALI. Through the CD44 receptor, HA-PEI could target the liver actively, with the highest liver-targeting effect confirmed at 1000 K. The underlying mechanism of protection of HA-PEI is by increasing oxygen content, reducing ROS, and maintaining mitochondrial membrane potential. HA-PEI also inhibits the secretion of inflammatory factors and blocks the migration of immune cells to the liver, protecting the hepatocytes not suffer from secondary damage. More importantly, for late-stage ALI, NAC, as the only FDA-approved drug, is completely ineffective, whereas HA-PEI has an excellent therapeutic effect. This work provides a new safe therapeutic agent for ALI, which has a bright application prospect.
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International Journal of Nanomedicine
·
2022
·
IF 7.033
Yue Dai,Xuan Sha,Xiaoxi Song,Xiuli Zhang,Mengyuan Xing,Siwen Liu,Kai Xu,Jingjing Li
Purpose Early diagnosis and treatment of atherosclerosis (AS) vulnerable plaque has important clinical significance for the prognosis of patients. In this work, the integrated diagnosis and treatment nanoparticles based on Gd-doped Prussian blue (GPB) were constructed for the fluorescence/MR dual-mode imaging and anti-ROS treatment of vulnerable AS plaques in vitro and in vivo. Methods To fabricate the theranostic NPs, GPB was modified with water-soluble polymer polyethyleneimine (PEI), fluorescence molecule rhodamine (Rd), and targeted molecule dextran sulfate (DS) step by step via electrostatic adsorption to construct GPRD NPs. The fluorescence/MR imaging ability and various nano-enzymes activity of GPRD NPs were detected, and the biocompatibility and safety of GPRD were also evaluated. Subsequently, RAW264.7 cells and ApoE -/- model mice were used to evaluate the effect of GPRD NPs on the targeted dual-mode imaging and anti-ROS treatment of vulnerable plaque in vitro and in vivo. Results The experimental results showed that our fabricated GPRD NPs not only displayed excellent MR/fluorescence dual-modality imaging of vulnerable plaque in vivo but also effectively utilized the nano-enzyme activity of GPB to inhibit the AS progress by ROS scavenging and the following reduction of inflammation, apoptosis, and foam cells’ formation, providing a new avenue for the diagnosis and treatment of AS vulnerable plaque. Conclusion The fabricated multimodal imaging nanoparticles with ROS-scavenging ability provided a new avenue for the diagnosis and treatment of AS vulnerable plaques.
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NEW JOURNAL OF CHEMISTRY
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2022
·Vol. 46
·期 44
·21235-21244
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IF 3.925
Huan Xu,Mingyue Yang,Yijing Du,Tian Gao,Yi Liu,Liwei Xiong,Na Peng
Nano-drug carriers have been widely used in chemotherapy to improve the efficacy of chemotherapeutic drugs. Polymer nano-carriers have greater potential for the enrichment of chemotherapeutic drugs at the target tumor site and controlled release. Herein, a series of amphiphilic copolymers (ITT) was synthesized via melt polymerization with a ROS-cleavable thioketal cross-linker, imidazole groups, and polyethylene glycol-conjugated triphenylphosphonium (PEG-TPP) segments; the actual proportions of the imidazole groups to the PEG-TPP segments were 5.2 : 1, 2.6 : 1, and 1.8 : 1, respectively. The amphiphilic copolymers could self-assemble into cationic micelles with hydrophobic imidazole groups as the core and hydrophilic PEG-TPP segments as the shell in deionized water. The cationic micelles with an average particle size of 124.6–187.3 nm showed a drug loading content (DLC) of 5.65–6.10%. In vitro release studies revealed the pH/ROS dual-responsiveness of the DOX-loaded ITT micelles, and the release behavior of DOX from the micelles strongly depended on the content of imidazole groups in the ITT micelles. Typically, the release of the encapsulated DOX was 27.2%, 30.0%, and 34.1% from DOX-loaded ITT-1 micelles in PBS (pH 6.5) containing 0, 100, and 500 μM H2O2, respectively. The release of the encapsulated DOX was 20.3%, 27.2%, and 42.5% from DOX-loaded ITT-1 micelles in PBS (pH 7.4), PBS (pH 6.5), and PBS (pH 5.0), respectively. The DOX-loaded micelles effectively inhibited the growth of 4T1 cells through being internalized into the 4T1 cells and releasing DOX into the mitochondria, with a cell viability of less than 65% when the DOX concentration was 2.5 μg mL−1. This work presents a novel mitochondria-targeting and pH/ROS-responsive polymer nanocarrier for potential chemotherapy applications.
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Current Research in Food Science
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2022
·
IF 6.269
Xuan Chen,Liufeng Zheng,Bing Zhang,Zeyuan Deng,Hongyan Li
Oxidative stress is a potential factor in the promotion of endothelial dysfunction. In this research, flavonoids (quercetin, luteolin) combined with carotenoids (lycopene, lutein), especially quercetin-lycopene combination (molar ratio 5:1), prevented the oxidative stress in HUVEC cells by reducing the reactive oxygen species (ROS) and suppressing the expression of NADPH oxidase 4 (Nox4), a major source of ROS production. RNA-seq analysis indicated quercetin-lycopene combination downregulated inflammatory genes induced by H 2 O 2 , such as IL-17 and NF-κB. The expression of NF-κB p65 was activated by H 2 O 2 but inhibited by the quercetin-lycopene combination. Moreover, the quercetin and lycopene combination promoted the thermostability of Sirtuin 1 (SIRT1) and activated SIRT1 deacetyl activity. SIRT1 inhibitor EX-527 attenuated the inhibitory effects of quercetin, lycopene, and their combination on the expression of p65, Nox4 enzyme, and ROS. Quercetin-lycopene combination could interact with SIRT1 to inhibit Nox4 and prevent endothelial oxidative stress, potentially contributing to the prevention of cardiovascular disease.
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MOLECULAR PHARMACEUTICS
·
2022
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IF 5.364
Han Sun,Ruihua Guo,Yanhui Guo,Jitao Song,Zhiliang Li,Fengling Song
As the most successful clinically approved photosensitizers, porphyrins have been extensively employed in the photodynamic therapy (PDT) of cancers. However, their poor water solubility, aggregation-induced self-quenching on ROS generation, and a low tolerance for a hypoxic condition usually result in unsatisfied therapeutic outcomes. Therefore, great efforts have been dedicated to improving the PDT efficacy of porphyrin-type photosensitizers in treating hypoxic tumors, including combination with additional active components or therapies, which can significantly complicate the therapeutic process. Herein, we report a novel water-soluble porphyrin with O-linked cationic side chains, which exhibits good water solubility, high photostability, and significantly enhanced ROS generation efficacy in both type-I and type-II photodynamic pathways. We have also found that the end charges of side chains can dramatically affect the ROS generation of the porphyrin. The cationic porphyrin exhibited high in vitro PDT efficacy with low IC50 values both in normoxia and hypoxia. Hence, during in vivo PDT study, the cationic porphyrin displayed highly effective tumor ablation capability. This study demonstrates the power of side-chain chemistry in tuning the photodynamic property of porphyrin, which offers a new effective strategy to enhance the anticancer performance of photosensitizers for fulfilling the increasing demands for cancer therapy in clinics.
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CHEMICAL ENGINEERING JOURNAL
·
2022
·
IF 16.744
Yue Wu,Chen Yuan,Xianjing Jia,Zhiyuan Zheng,Xijiao Yang,Jintao Yang,A. Basak Kayitmazer,Ayyaz Ahmad,Naveed Ramzan,Yisheng Xu
Dye-sensitized upconversion nanoparticles (UCNPs) have gained significant interest in biological applications. However, previous attempts to utilize these dye-sensitized UCNPs in the aqueous environment suffer from dramatic decline in the upconversion luminescence (UCL) intensity and problems with nanoparticles aggregation and water quenching. By employing indocyanine green (ICG) as a hydrophobic amplifier and energy harvester for UCNPs, we use a general, facile, and kinetically controlled mixing technology—flash nanoprecipitation (FNP)—to prepare aqueous stable ICG-sensitized UCNPs encapsulated by a biocompatible block copolymer poly (ethylene glycol)- b -poly (lactic- co -glycolic acid (PEG- b -PLGA) to efficiently activate ROS generation for simultaneous cancer cell imaging and treatment. As compared to NPs obtained from traditional drip and stir method (TM), the NPs under high turbulent conditions (high Re ) exhibit smaller size, narrower size distribution, and much higher stability, for the UCNPs hydrophobicity enhanced by ICG which was bound on the surface of UCNPs due to the coordination effect between sulfonates of ICG molecules and naked lanthanide metal ions of UCNPs. The remained UCL intensity was significantly boosted as well as ROS generation through FNP in the presence of ICG, but not for TM samples indicating superior protection of upconversion NPs from water quenching and the energy transfer between ICG and UCNP was well retained. The efficiency of ROS generation of NPs via FNP evidently increases with the stronger red-light emission of UCNPs, resulting in high cytotoxicity for SMMC-7721 cells in vitro and good suppression of tumor growth in vivo . The success of NPs by FNP in biological application demonstrates a bright prospect of FNP for synthesis of efficient antitumor nanoparticles.
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ACS Nano
·
2022
·
IF 18.027
Ruoyao Li,Yuanyuan Fan,Lulu Liu,Hongna Ma,Deyan Gong,Zhaohua Miao,Hua Wang,Zhengbao Zha
The exciting success of NBTXR3 in the clinic has triggered a tumult of activities in the design and development of hafnium-based nanoparticles. However, due to the concerns of nondegradation and limited functions, the biomedical applications of Hf-based nanoparticles mainly focus on tumors. Herein, tannic acid capped hafnium disulfide (HfS2@TA) nanosheets, a 2D atomic crystal of hafnium-based materials prepared by liquid-phase exfoliation, were explored as high-performance anti-inflammatory nanoagents for the targeted therapy of inflammatory bowel disease (IBD). Benefiting from the transformation of the S2–/S6+ valence state and huge specific surface area, the obtained HfS2@TA nanosheets were not only capable of effectively eliminating reactive oxygen species/reactive nitrogen species and downregulating pro-inflammatory factors but also could be excreted via kidney and hepatointestinal systems. Unexpectedly, HfS2@TA maintained excellent targeting capability to an inflamed colon even in the harsh digestive tract environment, mainly attributed to the electrostatic interactions between negatively charged tannic acid and positively charged inflamed epithelium. Encouragingly, upon oral or intravenous administration, HfS2@TA quickly inhibited inflammation and repaired the intestinal mucosa barrier in both dextran sodium sulfate and 2,4,6-trinitrobenzenesulfonic acid induced IBD models. This work demonstrated that ultrathin HfS2@TA atomic crystals with enhanced colon accumulation were promising for the targeted therapy of IBD.
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JOURNAL OF HAZARDOUS MATERIALS
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2022
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IF 14.224
Lirong Huang,Kun Jia,Haibin Xiong,Guiyou Tian,Jiaxin Xu,Wei Yuan,Chen Lu,Xiaoping Xiao,Huiqiang Lu
Nephrotoxicity of oxyfluorfen to vertebrates remains unclear despite its wide use as a herbicide. In order to further study its nephrotoxicity and its underlying mechanism, we used human embryonic kidney cells and zebrafish to explore. HEK293T cells were exposed to 2, 4, 6 μg/mL oxyfluorfen for 24 h in vitro, and zebrafish were exposed to 0.4, 0.8, 1.2 mg/L oxyfluorfen for 72 h in vivo. We found that oxyfluorfen inhibits cell migration and induces oxidative stress and apoptosis, causing kidney damage or nephrotoxicity in embryonic and adult zebrafish. Oxyfluorfen triggered inflammation in zebrafish and causing severe periorbital and body edema in embryos. Oxyfluorfen induced the secretion of kidney injury markers, including urea nitrogen (BUN), creatinine (CR), and β-n-acetyl-glucosaminidase (NAG) in zebrafish. Additionally, oxyfluorfen affected the homeostasis of oxidant and antioxidant systems, leading to reactive oxygen species (ROS) overload. Oxyfluorfen also damaged the glomerular podocytes and induced apoptosis of proximal tubules, which is harmful to normal body function and the renal filtration system. These results indicate that oxyfluorfen is a potential environmental hazard that can cause severe kidney injury and affect the health of organisms.
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