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JOURNAL OF COLLOID AND INTERFACE SCIENCE · 2024 · IF 9.4

Amino acid-based metallo-supramolecular nanoassemblies capable of regulating cellular redox homeostasis for tumoricidal chemo-/photo-/catalytic combination therapy

Li Tu,Shengqiang Chen,Zhikang Yuan,Yeqi Xiong,Bingkun Luo,Ying Chen,Zhenqing Hou,Sunkui Ke,Naibo Lin,Chao Li,Shefang Ye

Nanozymes, as nanomaterials with natural enzyme activities, have been widely applied to deliver various therapeutic agents to synergistically combat the progression of malignant tumors. However, currently common inorganic nanozyme-based drug delivery systems still face challenges such as suboptimal biosafety, inadequate stability, and inferior tumor selectivity. Herein, a super-stable amino acid-based metallo-supramolecular nanoassembly (FPIC NPs) with peroxidase (POD)- and glutathione oxidase (GSHOx)-like activities was fabricated via Pt 4+ -driven coordination co-assembly of l -cysteine derivatives, the chemotherapeutic drug curcumin (Cur), and the photosensitizer indocyanine green (ICG). The superior POD- and GSHOx-like activities could not only catalyze the decomposition of endogenous hydrogen peroxide into massive hydroxyl radicals, but also deplete the overproduced glutathione (GSH) in cancer cells to weaken intracellular antioxidant defenses. Meanwhile, FPIC NPs would undergo degradation in response to GSH to specifically release Cur, causing efficient mitochondrial damage. In addition, FPIC NPs intrinsically enable fluorescence/photoacoustic imaging to visualize tumor accumulation of encapsulated ICG in real time, thereby determining an appropriate treatment time point for tumoricidal photothermal (PTT)/photodynamic therapy (PDT). In vitro and in vivo findings demonstrated the quadruple orchestration of catalytic therapy, chemotherapeutics, PTT, and PDT offers conspicuous antineoplastic effects with minimal side reactions. This work may provide novel ideas for designing supramolecular nanoassemblies with multiple enzymatic activities and therapeutic functions, allowing for wider applications of nanozymes and nanoassemblies in biomedicine.

CAS / MDL: 3317-61-1
研究领域: 纳米技术 · 癌症治疗 · 生物医学工程 · 材料科学
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INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES · 2024 ·Vol. 25 ·期 11 ·5939 · IF 4.9

Petanin Potentiated JNK Phosphorylation to Negatively Regulate the ERK/CREB/MITF Signaling Pathway for Anti-Melanogenesis in Zebrafish

Jian Ouyang,Na Hu,Honglun Wang

Petanin, an acylated anthocyanin from the Solanaceae family, shows potential in tyrosinase inhibitory activity and anti-melanogenic effects; however, its mechanism remains unclear. Therefore, to investigate the underlying mechanism of petanin’s anti-melanogenic effects, the enzyme activity, protein expression and mRNA transcription of melanogenic and related signaling pathways in zebrafish using network pharmacology, molecular docking and molecular dynamics simulation were combined for analysis. The results showed that petanin could inhibit tyrosinase activity and melanogenesis, change the distribution and arrangement of melanocytes and the structure of melanosomes, reduce the activities of catalase (CAT) and peroxidase (POD) and enhance the activity of glutathione reductase (GR). It also up-regulated JNK phosphorylation, inhibited ERK/RSK phosphorylation and down-regulated CREB/MITF-related protein expression and mRNA transcription. These results were consistent with the predictions provided through network pharmacology and molecular docking. Thus, petanin could inhibit the activity of tyrosinase and the expression of tyrosinase by inhibiting and negatively regulating the tyrosinase-related signaling pathway ERK/CREB/MITF through p-JNK. In conclusion, petanin is a good tyrosinase inhibitor and anti-melanin natural compound with significant market prospects in melanogenesis-related diseases and skin whitening cosmetics.

CAS / MDL: 497-76-7
研究领域: 药理学 · 生物化学 · 分子生物学 · 斑马鱼研究 · 化妆品科学
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CHEMICAL ENGINEERING JOURNAL · 2024 · IF 13.3

Multi-Enzyme Co-Expressed Ruthenium dioxide nanoparticles activate mitochondrial autophagy and regulate oxidative stress for Alzheimer's disease treatment

Yutong Chen,Ji-an Wei,Liqiang Wang,Qianyu Cai,Fang Yang,Li Zhang,Jie Liu,Yanan Liu

Mitochondrial damage induced by reactive oxygen species and mitochondrial autophagy dysfunction are closely related to the pathogenesis of Alzheimer's disease (AD). Therefore, the recovery of mitochondrial autophagy disorder is crucial in maintaining mitochondrial homeostasis, protecting neurons, and improving AD. Herein, Ruthenium dioxide nanoparticles (RuO 2 ) have multi-enzyme activities, such as superoxide dismutase (SOD), catalase (CAT) and peroxidase (POD). And the multi-enzyme activity depends on the size, oxygen vacancy, morphology and specific surface area of the nanoparticles. The ultrasmall Ruthenium dioxide showed excellent antioxidant activity in the enzyme activity experiment. The results of in vitro experiments show that RuO 2 can restore damaged neurons by clearing Aβ and H 2 O 2 -induced reactive oxygen species (ROS). It maintains mitochondrial function, restores mitochondrial autophagy and normalizes mitochondrial dysfunction, thereby restoring injured neuronal cells. At the same time, it also showed the ability to regulate microglia polarization, inhibit microglia overactivation, and relieve neuroinflammation. After screening the results of enzyme activity experiment and in vitro experiment, sRuO 2 with small particle size and good enzyme activity was selected for in vivo experiment. sRuO 2 can inhibit oxidative stress in vivo , reduce the burden of Aβ, regulate the neuroprotective function of microglia and improve neuroinflammation. It ultimately improve memory decline and cognitive impairment in Aβ mice. These results suggest that sRuO 2 nanoenzymes with antioxidant activity have great potential in the treatment of AD. The multi-target strategy also offers a promising treatment option for AD.

CAS / MDL: 54827-17-7
研究领域: 神经科学 · 纳米技术 · 药理学 · 分子生物学
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Small · 2021 ·Vol. 17 ·期 7 ·2005865 · IF 13.281

Multienzyme-Mimic Ultrafine Alloyed Nanoparticles in Metal Organic Frameworks for Enhanced Chemodynamic Therapy

Peipei Yang,Jia Tao,Fengfeng Chen,Yuying Chen,Jiaqi He,Kui Shen,Peng Zhao,Yingwei Li

Nanozyme-based chemodynamic therapy (CDT) has emerged as an effective cancer treatment because of its low side effects and without the requirement of exogenous energy. The therapeutic effect of CDT highlights the pivotal importance of active sites, H 2 O 2 supplement and the glutathione (GSH) depletion of a nanozyme. The construction of a single kind of catalyst with multiple functions for the enhanced CDT is still a big challenge. In this work, seven types of bimetallic nanoparticles are synthesized using a metal–organic framework (MOF) as a stable host instead of a Fenton or Fenton-like ions supplier. Among them, Cu-Pd@MIL-101 with an alloy loading of 9.5 wt% modified by PEG (9.5% CPMP) is found to exhibit the highest peroxidase (POD) like activity combined with a superoxide dismutase (SOD) mimic activity and the function of GSH depletion. The in vivo results suggest that the stable and ultrafine nanoparticles possess favorable CDT effect for tumor and good biosafety as well as biocompatibility. This work has provided a credible strategy to construct nanozymes with an excellent activity and may pave a new way for the design of enhanced tumor CDT treatment.

研究领域: 纳米技术 · 癌症治疗 · 材料科学 · 生物化学 · 生物医学工程
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COLLOIDS AND SURFACES B-BIOINTERFACES · 2023 · IF 5.8

High aspect ratio plasmonic Au/Ag nanorods-mediated NIR-II photothermally enhanced nanozyme catalytic cancer therapy

Xinyu Cui,Minghui Li,Lei Tong,Miaojing Li,Xuefeng Tang,Xiaojun Han

Chemodynamic therapy (CDT) is based on the endogenous generation of cytotoxic hydroxyl free radicals (·OH) with high specificity and selectivity between cancer and normal cells. However, its efficacy is often limited by the relatively deficient catalytic activity of nanozymes in the tumor microenvironment (TME). Therefore, the combination of CDT with other strategy to realize synergistic therapy is necessary. Herein, a versatile plasmonic Au/Ag nanorods (abbreviated as Au/Ag NRs) via anisotropic Ag overgrowth on Au nanobipyramids was rationally devised to achieve synergistic nanozyme catalytic therapy and near infrared II (NIR-II) light induced photothermal therapy (PTT) with the guidance of computed tomography (CT) imaging. As TME contains high concentrations of H + and H 2 O 2 , Au/Ag NRs exhibited peroxidase (POD) activity to catalyze H 2 O 2 to produce ·OH, inducing cancer cell death. Meanwhile, Au/Ag NRs showed a preeminent NIR-II photothermal effect. More importantly, the enhanced ·OH generation by in-situ heating up resulting from PTT could conversely inhibit the expression of heat shock proteins (HSPs) to abate their resistance to PTT, realizing self-augmented synergistic effect. The NIR-II photothermally enhanced nanozyme catalytic cancer therapy validly inhibited the cancer proliferation, as demonstrated via both cell and animal assays. Moreover, ideal high-contrast CT imaging was realized, owing to the X-ray attenuation capability of elemental Au. The multifunctional Au/Ag NRs hold potential in oncotherapy with imaging capability, high efficiency and low side effects.

研究领域: 癌症治疗 · 纳米技术 · 光热治疗 · 纳米酶 · 成像技术
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Materials Research Express · 2024 · IF 1.8

PdCu nanoparticles with multienzymatic activity to treat tumors through the synergistic photothermal and chemodynamic therapy

Wende Fan,Yulin Xie,Yinyuan Zhang,Xiaoju Li,Chunxia Li

Combined chemodynamic/photothermal therapy has great potential in tumor treatment. However, the presence of excessive glutathione (GSH) in the tumor microenvironment (TME) can attenuate its therapeutic effect, and other components in the TME have not been fully utilized as well. In this article, we designed a noble metal nanozyme called PdCu@BSA, which can be used for the combined chemodynamic therapy (CDT) and photothermal therapy (PTT) of tumor. In detail, PdCu@BSA has three different types of enzyme-like activities. Its catalase (CAT)-like activity can degrade extra H2O2 in the TME to create O2 and relieve the hypoxic situation. The glutathione oxidase (GSHox)-like activity can consume high level of GSH in the TME to reduce the consumption of reactive oxygen species (ROS). Peroxidase (POD)-like activity catalyzes H2O2 to form strong oxidized ·OH. The above enzyme-like activities enhance the effectiveness of CDT. Besides, PdCu@BSA has good photothermal effect and can be used for PTT when exposed to 1064 nm laser. Therefore, based on multiple enzyme-like activities and photothermal effects, PdCu@BSA can be employed for synergistic tumor therapy, resulting in good therapeutic outcome.

研究领域: 纳米技术 · 癌症治疗 · 生物医学工程 · 材料科学 · 生物化学
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ACS Applied Nano Materials · 2023 · IF 5.9

Ligand Engineering of Gold Nanoclusters for NIR-II Imaging

Meili Guo,Gang Zhang,Ruoli Zhao,Huizhen Ma,Yuxing Yan,Shuyu Yang,Jian Meng,You Huang,Xiao-Dong Zhang,Hao Wang,Ruiping Zhang

Near-infrared-II (NIR-II) imaging has shown great potential in medical diagnosis and surgical navigation, but developing safe, photostable, high-brightness molecular probes remains a great challenge. Due to their ultrasmall size resulting in highly efficient renal clearance, gold nanoclusters have shown great clinical potential. In this work, we systematically explored the effect of different ligands on the luminescence and bioactivity of gold nanoclusters. Our results show that gold nanoclusters protected by thioglycolic acid (TGA) and 6-mercaptohexanoic acid (MHA) exhibit the strongest fluorescence, while 3-mercaptopropionic acid (MPA)- and sodium sulfide (Na2S)-protected gold nanoclusters show the weakest NIR-II signal. Further doping showed that the Cd-doped MPA and MHA-protected gold nanoclusters exhibited enhanced fluorescence, but the cysteine (Cys)-, glutathione (GSH)-, and Na2S-protected gold nanoclusters showed fluorescence quenching after doping, indicating significant ligand selectivity. Because of the unique multi-energy structure and the large number of electronic states at the highest occupied molecular orbital energy level, MPA- and MHA-protected gold nanoclusters exhibit high stability and photostability. In addition, gold nanoclusters with different ligands exhibited different selective enzyme-mimicking activities of peroxidase (POD), superoxide dismutase (SOD), and catalase (CAT). Imaging in vivo showed that gold nanoclusters could accomplish reliable imaging of cerebral vasculature, hindlimb vessels, and spine as well as monitor renal clearance. The stable nanoclusters allow the time window of imaging to reach 125 min for hindlimb imaging and 270 min for spinal imaging. The gold nanoclusters exhibit a high signal-to-noise ratio of up to 11 for whole-body imaging and show efficient renal clearance and low toxicity at an injected dose of 50 mg/kg.

研究领域: 生物医学工程 · 纳米技术 · 医学成像 · 材料科学
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JOURNAL OF NANOBIOTECHNOLOGY · 2024 ·Vol. 22 ·期 1 ·1-19 · IF 10.6

A thermo-sensitive hydrogel with prominent hemostatic effect prevents tumor recurrence via anti-anoikis-resistance

Liu Yang,Ding Lei,Chen Gaojie,Wang Peiyuan,Wang Xinghuan

Tumor cells can survive when detached from the extracellular matrix (ECM) or lose cell–cell connections, a phenomenon known as anoikis-resistance (AR). AR is closely associated with tumor cell metastasis and recurrence, enabling tumor cells to disseminate, migrate, and invade after detachment. To address this issue, a novel intervention method combining intraoperative hemostasis with multifunctional nanozyme driven-enhanced chemodynamic therapy (ECDT) has been proposed, which holds the potential to weaken the AR capability of tumor cells and suppress tumor recurrence. Here, a nanocomposite containing a dendritic mesoporous nanoframework with Cu 2+ was developed using an anion-assisted approach after surface PEG grafting and glucose oxidase (GOx) anchoring (DMSN-Cu@GOx/PEG). DMSN-Cu@GOx/PEG was further encapsulated in a thermal-sensitive hydrogel (H@DMSN-Cu@GOx/PEG). DMSN-Cu@GOx/PEG utilizes its high peroxidase (POD) activity to elevate intracellular ROS levels, thereby weakening the AR capability of bladder cancer cells. Additionally, through its excellent catalase (CAT) activity, DMSN-Cu@GOx/PEG converts the high level of hydrogen peroxide (H 2 O 2 ) catalyzed by intracellular GOx into oxygen (O 2 ), effectively alleviating tumor hypoxia, downregulating hypoxia-inducible factor-1α (HIF-1α) expression, inhibiting epithelial-mesenchymal transition (EMT) processes, and ultimately suppressing the migration and invasion of bladder cancer cells. Interestingly, in vivo results showed that the thermosensitive hydrogel H@DMSN-Cu@GOx/PEG could rapidly gel at body temperature, forming a gel film on wounds to eliminate residual tumor tissue after tumor resection surgery. Importantly, H@DMSN-Cu@GOx/PEG exhibited excellent hemostatic capabilities, effectively enhancing tissue coagulation during post-tumor resection surgery and mitigating the risk of cancer cell dissemination and recurrence due to surgical bleeding. Such hydrogels undoubtedly possess strong surgical application. Our developed novel nanosystem and hydrogel can inhibit the AR capability of tumor cells and prevent recurrence post-surgery. This study represents the first report of using dendritic mesoporous silica-based nanoreactors for inhibiting the AR capability of bladder cancer cells and suppressing tumor recurrence post-surgery, providing a new avenue for developing strategies to impede tumor recurrence after surgery. Graphical Abstract

研究领域: 生物医学工程 · 纳米技术 · 癌症生物学 · 材料科学
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ACS Applied Materials & Interfaces · 2020 · IF 8.758

Self-Assembled Multiple-Enzyme Composites for Enhanced Synergistic Cancer Starving–Catalytic Therapy

Huihui Wang,Lu Cheng,Shang Ma,Liming Ding,Wei Zhang,Zhuobin Xu,Dandan Li,Lizeng Gao

Inspired by the particularity of tumor microenvironments, including acidity and sensibility to reactive oxygen species (ROS), advanced and smart responsive nanomaterials have recently been developed. The present study synthesized tumor-targeted and pH-sensitive supramolecular micelles that self-assembled via host–guest recognition. The micelles consumed intratumoral glucose and lactate via loading with glucose oxidase (GOD) and lactate oxidase (LOD). Intratumoral glucose and lactate were converted into hydrogen peroxide (H2O2) and were sequentially reduced to highly toxic hydroxyl radicals (•OH) via the peroxidase (POD)-like activity of the loaded C-dot nanozymes. Tumor-killing effects were observed via cascade catalytic reactions. After an intravenous injection, the nanocomposite exhibited an excellent tumor-targeted ability with good biocompatibility, which demonstrated its effective antitumor effect. The nanocomposite effectively combined starvation and catalytic therapies and exerted a synergistic anticancer effect with minimal side effects and without external addition.

研究领域: 纳米技术 · 生物医学工程 · 癌症治疗 · 生物化学 · 分子生物学
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Small · 2024 · IF 13

A Hybrid Alloying Nanozyme-Glutathione Inhibitor Co-Delivery System Initiates a Dual-Disruption on Cancer Redox Homeostasis

Jue Hou,Hanxiao Bao,Yu Wang,Qiaomei Zhou,Jiayi Chen,Guohua Pan,Guoqiao Xu,Jinguo Zhang,Guping Tang,Hongzhen Bai

Altered redox homeostasis has long been observed in cancer cells, which can be exploited for therapeutic benefits. However, reactive oxygen species (ROS) pleiotropy coupling with reductive adaptation in cancer cells poses a formidable challenge for redox dyshomeostasis-based cancer therapy. Herein, a AuPd alloying nanozyme-glutathione (GSH) biosynthesis inhibitor co-delivery system (B-BMES) is developed using dendritic SiO 2 as a matrix to target cancer redox homeostasis. By optimizing element composition, the alloying nanozyme in B-BMES exhibits a potent peroxidase (POD)-like activity to trigger ROS insults-mediated redox dyshomeostasis. Such a POD functionality is attributed to the optimized electronic structure and catalytic activity. Simultaneously, the B-BMES abrogates the reductive adaptation by exerting its molecule-targeted GSH suppression, thereby achieving a dual-disruption on cancer redox homeostasis. Camouflaging B-BMES with tumor-homologous cytomembrane, a hybrid nanosystem with biological stability and tumor-targeting ability is further fabricated, which initiates a safe, precise redox disruption-based cancer therapy and sensibilizes standard chemotherapy.

研究领域: 纳米技术 · 癌症治疗 · 氧化还原生物学 · 药物递送系统 · 材料科学 · 生物化学
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Acta Biomaterialia · 2023 · IF 9.7

Bimetallic oxide Cu-Fe3O4 nanoclusters with multiple enzymatic activities for wound infection treatment and wound healing

Xu Jin,Jie Shan,Jiemin Zhao,Tao Wang,Wei Zhang,Shijie Yang,Haisheng Qian,Liang Cheng,Xu-Lin Chen,Xianwen Wang

Infections and oxidative stress complicate wound healing. In recent years, nanomaterials with natural enzymatic activities have enabled the development of new antibacterial pathways. In this study, Cu-Fe 3 O 4 nanoclusters with multienzyme properties were synthesised. Interestingly, they exhibited activity similar to that of horseradish peroxidase (POD) in acidic environments but their functions resembled superoxide dismutase and catalase in neutral or weakly alkaline environments. In vitro studies have demonstrated the good free-radical scavenging activity of Cu-Fe 3 O 4 nanoclusters in a neutral environment. Under acidic conditions, Cu-Fe 3 O 4 nanoclusters combined with H 2 O 2 demonstrated good antibacterial activity against methicillin-resistant Staphylococcus aureus ( MRSA ) and Escherichia coli ( E. coli ). The combination of Cu-Fe 3 O 4 and H 2 O 2 was found to be effective in preventing MRSA infections and promoting wound healing in animal models. RNA sequencing (RNA-seq) technology revealed that chemodynamic therapy (CDT) using nanoparticles can interfere with metabolic processes such as galactose metabolism in MRSA bacteria, destroy the transport system on the surface of MRSA , and affect quorum sensing to hinder the formation of biofilms, thus achieving effective antibacterial efficacy. The use of Cu-Fe 3 O 4 nanoclusters as a novel class of multi-catalytically active nanozymes in the anti-infection of disease-causing pathogens and wound healing has significant potential. Statement of Significance Cu-Fe 3 O 4 nanoclusters with multienzyme properties were successfully prepared by a solvothermal method. Cu-Fe 3 O 4 nanoclusters exhibited horseradish peroxidase (POD)-like activity in acidic environments and also showed synergistic effects similar to superoxide dismutase peroxidase in neutral or weakly basic environments. More importantly, these Cu-Fe 3 O 4 nanoclusters showed high biosafety with no apparent in vivo toxicity. Chemodynamic therapy (CDT) using Cu-Fe 3 O 4 nanoclusters was revealed by RNA sequencing (RNA-Seq) technology to interfere with the metabolic processes of MRSA bacteria, such as galactose metabolism, disrupt the MRSA surface transport system, and impede biofilm formation, resulting in effective antibacterial efficacy. The use of Cu-Fe 3 O 4 nanoclusters for anti-infection and wound healing of pathogenic pathogens has significant potential as a novel class of multi-catalytic active nanoclusters.

研究领域: 纳米技术 · 生物医学工程 · 伤口愈合 · 抗菌治疗 · 酶模拟
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ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY · 2024 · IF 6.2

Niclosamide subacute exposure alters the immune response and microbiota of the gill and gut in black carp larvae, Mylopharyngodon piceus

Hao Wu,Xiping Yuan,Yong He,Jinwei Gao,Min Xie,Zhonggui Xie,Rui Song,Dongsheng Ou

Niclosamide (NIC) is a commonly used insecticide and molluscicide in the prevention and treatment of parasitic diseases in fish. The utilization of NIC has the potential to disrupt the microbial community present on the mucosal tissue of fish, leading to localized inflammatory responses. The objective of this study was to evaluate the impact of NIC on the immune system and bacterial populations within the gill and gut of Mylopharyngodon piceus . Fish were subjected to varying concentrations of NIC, including a control group (0 μg/L), a low NIC group (15% 96 h LC50, LNG, 9.8 μg/L), and a high NIC group (80% 96 h LC50, HNG, 52.5 μg/L). Gill and gut samples were collected 28 days post-exposure for analysis. The findings revealed that the 96-h LC 50 for NIC was determined to be 65.7 μg/L, and histopathological examination demonstrated that exposure to NIC resulted in gill filament subepithelial edema, exfoliation, degeneration, and a decrease in gill filament length. Furthermore, the gut exhibited apical enterocyte degeneration and leucocyte infiltration following NIC exposure. Additionally, NIC exposure led to a significant elevation in the levels of immunoglobulin M (IgM), complement component 3 (C3), and complement component 4 (C4) in both gill and gut tissues. Moreover, the activity of lysozyme (LYZ) was enhanced in the gill, while the activities of peroxidase (POD) and immunoglobulin T (IgT) were increased in gut tissue. The exposure to NIC resulted in enhanced mRNA expression of c3 , c9 , tnfα , il6 , il8 , and il11 in the gill tissue, while decreasing c3 and il8 expression in the gut tissue. Furthermore, the natural resistance-associated macrophage protein ( nramp ) mRNA increased, and liver-expressed antimicrobial peptide 2 ( leap2 ) mRNA decreased in gill and gut tissues. And hepcidin ( hepc ) mRNA levels rose in gill but fell in gut tissue. NIC exposure also led to a decrease in gill bacterial richness and diversity, which significantly differed from the control group, although this separation was not significant in the gut tissue. In conclusion, the administration of NIC resulted in alterations in both the immune response and mucosal microbiota of fish. Furthermore, it was noted that gills displayed a heightened vulnerability to sublethal effects of NIC in comparison to gut tissues.

CAS / MDL: 50-65-7
研究领域: 水生毒理学 · 免疫学 · 微生物学 · 鱼类生物学
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