PHYTOTHERAPY RESEARCH
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2023
·
IF 7.2
Yuan Zhu,Wei-feng Yin,Pei Yu,Chao Zhang,Ming-hui Sun,Ling-yi Kong,Lei Yang
Distal metastases from breast cancer, especially bone metastases, are extremely common in the late stages of the disease and are associated with a poor prognosis. EMT is a biomarker of the early process of bone metastasis, and MMP-9 and MMP-13 are important osteoclastic activators. Previously, we found that meso-Hannokinol (HA) could significantly inhibit EMT and MMP-9 and MMP-13 expressions in breast cancer cells. On this basis, we further explored the role of HA in breast cancer bone metastasis. In vivo, we established a breast cancer bone metastasis model by intracardially injecting breast cancer cells. Intraperitoneal injections of HA significantly reduced breast cancer cell metastasis to the leg bone in mice and osteolytic lesions caused by breast cancer. In vitro, HA inhibited the migration and invasion of breast cancer cells and suppressed the expressions of EMT, MMP-9, MMP-13, and other osteoclastic activators. HA inhibited EMT and MMP-9 by activating the ROS/JNK pathway as demonstrated by siJNK and SP600125 inhibition of JNK phosphorylation and NAC scavenging of ROS accumulation. Moreover, HA promoted bone formation and inhibited bone resorption in vitro. In conclusion, our findings suggest that HA may be an excellent candidate for treating breast cancer bone metastasis.
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Acta Biomaterialia
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2023
·
IF 9.7
Xin Shi,Tong Zhou,Shenyu Huang,Yuejun Yao,Peifang Xu,Shaodan Hu,Chenxi Tu,Wei Yin,Changyou Gao,Juan Ye
s Ocular alkali burn is a serious ophthalmic emergency. Highly penetrative alkalis cause strong inflammatory responses leading to persistent epithelial defects, acute corneal perforation and severe scarring, and thereby persistent pain, loss of vision and cicatricial sequelae. Early and effective anti-inflammation management is vital in reducing the severity of injury. In this study, a double network biomaterial was prepared by compounding electrospinning nanofibres of thioketal-containing polyurethane (PUTK) with a reactive oxygen species (ROS)-scavenging hydrogel (RH) fabricated by crosslinking poly(poly(ethylene glycol) methyl ether methacrylate-co-glycidyl methacrylate) with thioketal diamine and 3,3′-dithiobis(propionohydrazide). The developed PUTK/RH patch exhibited good transparency, high tensile strength and increased hydrophilicity . Most importantly, it demonstrated strong antioxidant activity against H 2 O 2 and 2,2-di(4-tert-octylphenyl)-1-picryl-hydrazyl (DPPH). Next, a rat corneal alkali burn model was established, and the PUTK/RH patch was transplanted on the injured cornea. Reduced inflammatory cell infiltration was revealed by confocal microscopy , and lower expression levels of genes relative to inflammation, vascularization and scarring were identified by qRT-PCR and western blot. Fluorescein sodium dyeing, hematoxylin and eosin (H&E) staining and immunohistochemical staining confirmed that the PUTK/RH patch could accelerate corneal wound healing by inhibiting inflammation, promoting epithelial regeneration and decreasing scar formation. Statement of significance Ocular alkali burn is a serious ophthalmic emergency, characterized with persistent inflammation and irreversible vision loss. Oxidative stress is the main pathological process at the acute inflammatory stage, during which combined use of glucocorticoids and amniotic membrane transplantation is the most widely accepted treatment. In this study, we fabricated a polyurethane electrospun nanofiber membrane functionalized with a ROS-scavenging hydrogel. This composite patch could be a promising amniotic membrane substitute, possessing with a transparent appearance, elasticity and anti-inflammation effect. It could be easily transplanted onto the alkali-burned corneas, resulting in a significant inhibition of stromal inflammation and accelerating the recovery of corneal transparency. The conception of ROS-scavenging wound patch may offer a new way for ocular alkali burn.
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PLoS One
·
2023
·Vol. 18
·期 8
·e0289563
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IF 3.7
Dongdong Cao,Yutao Huang,Gaofu Mei,Sheng Zhang,Huaping Wu,Tiyuan Zhao
Chilling stress is an important constraint for kale seed germination and seedlings establishment. It is vital to develop an effective approach to enhance kale seed germination ability under chilling stress. The present study reported that spermidine (Spd) could improve seed chilling tolerance in two kale cultivars ‘Nagoya’ (MGW) and ‘Pigeon’ (BB) during germination. The results showed that MGW was cold tolerant with a 90.67% germination percentage (GP) under chilling stress, while BB was cold sensitive with a 70.67% GP under chilling stress. Spd content in MGW and BB seeds during seed germination were up-regulated and down-regulated by chilling stress, respectively. Besides, chilling stress apparently decreased the gibberellin (GA) and ethylene (ET) contents, while increased the levels of abscisic acid (ABA) and reactive oxygen species (ROS) in MGW and BB seeds during germination. Exogenous Spd application increased GA, ET contents and decreased ABA content through regulating the gene expressions of metabolic-related enzymes, thus effectively alleviating the low temperature damage on kale seed germination. Besides, Spd significantly increased the activities of superoxide dismutase (SOD) and peroxidase (POD), and reduced the levels of hydrogen peroxide (H 2 O 2 ) and superoxide anion (O 2 · - ). The present study demonstrated that endogenous Spd metabolism plays an important role in kale seed germination under chilling stress. The effect of exogenous Spd on the metabolism of endogenous Spd, GA, ABA, ET and antioxidant enzymes might be the important reason for promoting the kale seed vigor at low temperature.
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FISH & SHELLFISH IMMUNOLOGY
·
2023
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IF 4.7
Zhiying Miao,Zhiruo Miao,Shuang Feng,Shiwen Xu
Chlorpyrifos (CPF) is a typical organophosphate insecticide known to has serious toxicological effects on aquatic animals and causes many environmental contamination problems. To assess the effects of CPF on the epithelioma papulosum cyprini (EPC) cells of the common carps from the point of calcium ion (Ca 2+ ) transport, the CPF-exposed EPC models were primarily established, and both AO/EB staining and Annexin V/PI assay with flow cytometry analysis were subsequently implemented to identify that CPF-induced EPC cell apoptosis, in consistent with the up-regulated expression of BAX, Cyt- c , CASP3 and CASP9, and down-regulated BCL-2 expression. Then, Mag-Fluo-4 AM, Fluo-4 AM and Rhod-2 AM staining probes were co-stained with ER-Tracker Red and Mito-Tracker Green applied to image cellular Ca 2+ flux, illuminating Ca 2+ depleted from ER and flux into mitochondria, resulting in ER stress and mitochondrial dysfunction. Additionally, 2-Aminoethyl Diphenylborinate (2-APB), 4-Phenylbutyric acid (4-PBA) and Dorsomorphin (Compound C) were performed as the inhibitor of Ca 2+ transition, ER stress and AMPK phosphorylation, suggesting CPF-mediated Ca 2+ overload triggered ER stress. And the over-generation of Mito-ROS intensified oxidative stress , promoting the phosphorylation of AMPK and deteriorating cell apoptotic death. The results of this study demonstrated Ca 2+ overload-dependent mitochondrial dysfunction engages in the CPF-induced apoptosis, providing a novel concept for investigating the toxicity of CPF as environmental pollution on aquatic organisms .
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ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH
·
2022
·Vol. 30
·期 5
·12125-12137
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IF 5.19
Yan Jin,Zou Ying,Zhang Fengrui,Zhang Shenghua,Huang Xinyue,Benoit Gaboury
Although the addition of triclosan (TCS) in consumer products has been strictly restricted, its continuous applications in hospitals and other medical facilities and its numerous residues still pose a potential risk to aquatic organisms and aquatic ecosystems. In this study, we investigated the growth, biochemical alterations, and physiological responses of Chlorella vulgaris exposed to different concentrations of TCS. The potential toxicity mechanisms associated with excessive production of reactive oxygen species (ROS) and disruption of photosynthetic system II (PSII) were also analyzed. The results indicated that the growth, cellular ultrastructure, and physiology of C. vulgaris were severely affected by TCS in a dose-effect dependent manner. TCS inhibited the growth of C. vulgaris , leading to mitochondria enlargement, the disordering of the arrangement of thylakoids, cell wall rupture, organelles loss, and the cytoplasm lysis. TCS induced severe oxidative damage characterized by ROS accumulation, elevated malondialdehyde (MDA), and up-regulation of antioxidant enzyme activities. Moreover, in TCS-induced algal cells, the main sites of ROS accumulation were chloroplasts, mitochondria, and cell membranes, with ROS accumulating most in the mitochondria. In addition, TCS caused damage to the reaction center (RC inactivation), donor side (OEC damage), and accepted side (electron transport from Q A to Q B ) of PSII in C. vulgaris , leading to inhibition of photosynthetic activity. These results could provide novel insights into the mechanisms of TCS-induced ROS accumulation and photosynthetic inhibition in C. vulgaris , which would contribute to a deep understanding of TCS toxicity on algae.
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JOURNAL OF HAZARDOUS MATERIALS
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2022
·
IF 14.224
Guoliang Chen,Mingxing Wang,Panpan Zhu,Guixue Wang,Tingzhang Hu
As a newly-invented and highly-efficiency strobilurin fungicide , pyraoxystrobin (SYP-3343) has been recognized as a highly poisonous toxin for a variety of aquatic organisms. Nevertheless, the developmental toxicity and potential mechanism of SYP-3343 have not been well-documented. The results showed that SYP-3343 was relatively stable and maintained within the range of 20 % in 24 h, and the LC 50 value to embryos at 72 hpf was 17.13 μg/L. The zebrafish embryotoxicity induced by 1, 2, 4, and 8 μg/L SYP-3343 is demonstrated by repressive embryo incubation, enhancive mortality rate, abnormal heart rate, malformed morphological characteristic, and impaired spontaneous coiling, indicating SYP-3343 mostly exerted its toxicity in a dose- and time-dependent manner. Besides SYP-3343 was critically involved in regulating cell cycle, mitochondrial membrane potential, and reactive oxygen species production as well as zebrafish primary cells apoptosis, which can be mitigated using antioxidant N-acetyl- L -cysteine. A significant change occurred in total protein content, the biochemical indices, and antioxidant capacities owing to SYP-3343 exposure. Additionally, SYP-3343 altered the mRNA levels of heart development-, mitochondrial function-, and apoptosis-related genes in zebrafish embryos. These results indicated that SYP-3343 induced apoptosis accompanying reactive oxygen species-initiated mitochondrial dysfunction in zebrafish embryos.
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SEPARATION AND PURIFICATION TECHNOLOGY
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2022
·
IF 9.136
Wenwei Feng,Hui Lin,Andac Armutlulu,Jie Chen,Rui Liu,Ruzhen Xie,Bo Lai
A novel eco-friendly vanadium-mediated Magnéli phase titanium suboxide (V@Ti 4 O 7 ) was fabricated via ball-milling-vacuum sintering method. The presence of V improved the stability and electrochemical performance of Ti 4 O 7 , which significantly promoted the activation of persulfate (PS) for superior degradation of organic pollutant ciprofloxacin (CIP). The results show that V doping significantly facilitated the electron transfer process and enhanced the oxygen evolution potential. The redox cycle of V 3+ /V 4+ and V 4+ /V 5+ endows the electrode with high stability and enriched catalytic active sites for PS activation , which allows for 89.11% CIP removal after the 8 th reuse. Scavenging experiments and electron paramagnetic resonance (EPR) results revealed the contribution of reactive oxidant species (i.e., SO 4 − , OH and 1 O 2 ) for efficient CIP degradation in the E-V@Ti 4 O 7 -PS system, in which, OH was the dominant reactive species accounting for 53.09 % of CIP removal, resulting in efficient CIP mineralization (TOC > 86.51%). The results of this study provide a better understanding of the relationship between the nature of anode and electro-activation of PS, which can facilitate the electrode design and optimization of E-PS reactors.
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JOURNAL OF CONTROLLED RELEASE
·
2022
·
IF 11.467
Qixiong Zhang,Shanshan Li,Jiandong Ren,Xia He,Houkui Shi,Fuzhong Zhang,Hui Li,Rongsheng Tong
Due to its complexity, diversity and heterogeneity, melanoma is a kind of malignant tumor. It has been proved that the enhancement of anti-tumor immune response such as immunogenic cell death (ICD) is an important therapeutic strategy. In previous studies, we confirmed that dermatan sulfate (DS) from skin tissue could specifically homing to melanoma B16F10 cells. In this study, we propose a nanoinducer (DOX/ADS NP) based on a functional DS for melanoma. This nanosystem is composed of DS as framework, aromatic thioketal derivative (ATK) as functional grafting unit and doxorubicin (DOX) designed as an ICD inducer. Through the intermolecular interaction between DOX and ATK, DOX/ADS NP with specific-homing, high-loading and ROS-triggering release was obtained via self-assemble. Compared with free DOX and non-functionalized nanomedicine , DOX/ADS NP could release DOX into B16F10 cells better, and strongly induce the translocation of calreticulin (CRT) to the cell membrane . CRT is a marker of ICD, also as a “eat me” signal to stimulate the maturation and antigen presentation of dendritic cells. Therefore, a series of subsequent immune responses were activated: maturation of dendritic cells, T cells proliferation, increased tumor-infiltrating CTLs and the ratio of CTLs to Tregs, and up-regulated cytotoxic cytokine expression. In conclusion, DOX/ADS NP promoted ICD-associated immune response through more specific targeting effect and sensitive responsive DOX release, achieving better inhibitory effect on melanoma than free DOX and other nanoformulation. This biomimetic ICD nanoinducer based on DS is expected to provide new strategies and references for the treatment of melanoma.
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Bosnian Journal of Basic Medical Sciences
·
2022
·
IF 3.759
Peng Hua,Donglin Yang,Ruie Chen,Peiqi Qiu,Meiwan Chen
Cationic polymer polyethylenimine (PEI) plays a crucial role in gene delivery. However, high molecular weight PEI leads to higher efficient transfection efficacy and higher cytotoxicity, while low molecular weight PEI exhibits lower transfection performance with lower toxicity. Therefore, effective chemical modification of PEI is required to enhance transfection activity and improve biocompatibility. Here, reactive oxygen species (ROS) responsive PEI-based fluorinated polymers (TKPF) with three degrees of fluorination (TKPF 12.5%, TKPF 25%, and TKPF 50%) were designed and synthesized by crosslinking low molecular weight PEI (PEI 1.8K) with a thioketal (TK) linker and then modifying heptafluorobutyric anhydride onto their surface. Fluorination reduced the positive charge density and endowed hydrophobic and lipophobic characteristics to resist serum interactions. The fluorophilic effect mediated efficient cellular uptake and endosomal escape while ROS-responsive TK linker allowed the polyplex disassembly to decrease the cytotoxicity of the polycations and improve the release of payloads at specific sites. TKPFs attained superior transfection efficiency in multiple cell lines (293TN cells and B16F10 cells) in vitro and showed excellent biocompatibility. TKPFs also exhibited great serum resistance in gene delivery and TKPF 50% transfected nearly 80% cells in the presence of 70% FBS. These results demonstrate that the fluorination and ROS responsiveness combined polycations are excellent gene-delivery vectors with serum-resistant capacity for further application.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2022
·
IF 8.025
Chunjing Guo,Yanguo Su,Ziting Cheng,Qiang Chen,Huimin Guo,Ming Kong,Daquan Chen
Chemodynamic therapy (CDT) has been widely used in the treatment of many kinds of tumors, which can effectively induce tumor cell apoptosis by using produced reactive oxygen species (ROS). In this paper, ROS-sensitive multifunctional marine biomaterial natural polysaccharide nanoparticles were designed. Aggregation-induced emission (AIE) molecules tetraphenylethylene (TPE) labeled and caffeic acid (CA) modified fucoidan (FUC) amphiphilic carrier material (CA-FUC-TK-TPE, CFTT) was fabricated, in which the thioketal bond(TK) was used as the linkage arm between TPE and fucoidan chain, giving the CFTT material ROS sensitivity. In addition, amphiphilic carrier material (FUC-TK-VE, FTVE) composed of thioketal-linked vitamin E and fucoidan was synthesized. The mixed carrier material CFTT and FTVE self-assembled in water to form nanoparticles (CFTT – FTVE@PTX-Fe 3+ ) loaded with PTX and Fe 3+ . The CDT effect was combined with the chemotherapeutic drug PTX to achieve tumor inhibition. In vitro cell studies have proved that CT/PTX nanoparticles have excellent cell permeability and tumor cytotoxicity. In vivo antitumor experiments confirmed effective antitumor activity and reduced side effects.
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MACROMOLECULAR MATERIALS AND ENGINEERING
·
2022
·Vol. 307
·期 8
·2100987
·
IF 4.402
Yu Fang,Jing Wang,Ling-Yun Zou,Hong-Lin Qian,Ke-Feng Ren,You-Xiang Wang,Jian Ji
Mussel-inspired polydopamine (PDA) coating has been proved to be a universal surface modification strategy with remarkable versatility and active post-modification ability. However, the traditional preparation of PDA coating shows low polymerization efficiency and alkaline environment dependency. Herein, a robust method to accelerate the in situ generation of PDA coating based on a photosensitizer entrapped substrate is reported. It is demonstrated that the chlorin e6 (Ce6)-incorporated substrates induce sustained reactive oxygen species (ROS) production via laser irradiation at 660 nm, which dramatically promotes the preparation of PDA coating even in acidic conditions. The thickness of the PDA coating reaches over 4 nm with only 10 min irradiation (pH 6). Patterned PDA coatings can also be achieved by using a photomask. The functionality of this interfacial ROS-induced PDA coating including photothermal ability and secondary modification ability is also verified. The obtained PDA coating realizes the reduction of Ag + to Ag NPs, which shows excellent antibacterial ability. This interfacial ROS generation strategy offers a facile and efficient way to construct the PDA coating and expands the potential applications in the biomedical field.
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2023
·
IF 6.1
Sen Wang,Hui Ren,Chen Fan,Qian Lin,Man Liu,Jun Tian
Mycotoxin ochratoxin A (OTA) is a critical food safety concern due to its nephron-toxic effects and is detected in a wide range of food and feedstuffs. OTA nephrotoxicity is related to oxidative stress and damage. However, the mediator(s) of the excessive oxidative stress is unclear. The current study used human kidney cell lines to investigate whether and how intracellular iron contributed to OTA-induced ROS accumulation and how OTA-induced iron-dependent ferroptotic cell death. Our results showed that OTA treatment affected the cell viability and induced the typical characteristics of cell ferroptosis. Furthermore, gene and protein expression results indicated that OTA disrupted iron homeostasis by upregulating the expression levels of iron importer TFR1 and FTH, while downregulating the expression level of iron exporter FPN and dramatically increasing its negative regulator Hepcidin. The changes were consistent with the induction of intracellular iron accumulation and elevated levels of oxidative stress and lipid peroxidation. Additionally, co-treatment with OTA and an iron chelator significantly improved cell viability, reduced cellular total iron and ROS, and reversed OTA-induced changes in iron metabolism gene expression levels. Interestingly, the addition of a ROS scavenger also reversed cell death and changes in mRNA and protein expression levels of iron metabolism genes but to a lesser degree than that of the iron-chelating agent. Our results revealed that OTA induced ferroptosis in renal cells by disrupting iron homeostasis and increasing ROS.
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