INTERNATIONAL IMMUNOPHARMACOLOGY
·
2023
·
IF 5.6
Xin-Yu Shen,Jing-Mei Lu,Yu-Nan Lu,Guang-Nan Jin,Jing-Wen Ma,Jing-He Wang,Yu Wang,Xiang Xu,Lian-Xun Piao
Toxoplasma gondii ( T. gondii ) is an obligate intracellular protozoan parasite that causes pulmonary toxoplasmosis, although its pathogenesis is incompletely understood. There is no cure for toxoplasmosis. Coixol, a plant polyphenol extracted from coix seeds, has a variety of biological activities. However, the effects of coixol on T. gondii infection have not been clarified. In this study, we infected a mouse macrophage cell line (RAW 264.7) and BALB/c mice with the T. gondii RH strain to establish infection models in vitro and in vivo , respectively, to explore protective effects and potential mechanisms of coixol on lung injury caused by T. gondii infection. Anti- T. gondii effects and underlying anti-inflammatory mechanisms of coixol were investigated by real-time quantitative PCR, molecular docking, localized surface plasmon resonance, co-immunoprecipitation, enzyme-linked immunosorbent assay, western blotting, and immunofluorescence microscopy. The results show that coixol inhibits T. gondii loads and T. gondii -derived heat shock protein 70 ( T.g. HSP70) expression. Moreover, coixol reduced inflammatory cell recruitment and infiltration, and ameliorated pathological lung injury induced by T. gondii infection. Coixol can directly bind T.g. HSP70 or Toll-like receptor 4 (TLR4) to disrupt their interaction. Coixol prevented overexpression of inducible nitric oxide synthase, tumor necrosis factor-α, and high mobility group box 1 by inhibiting activation of the TLR4/nuclear factor (NF)-κB signaling pathway, consistent with effects of the TLR4 inhibitor CLI-095. These results indicate that coixol improves T. gondii infection-induced lung injury by interfering with T.g. HSP70-mediated TLR4/NF-κB signaling. Altogether, these findings suggest that coixol is a promising effective lead compound for the treatment of toxoplasmosis.
研究领域:
寄生虫学
·
免疫学
·
药理学
·
分子生物学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2025
·
IF 9.6
Yating Wang,Yixuan Xu,Dejia Chen,Xin Li,Dalong Yin,Lifeng Yan
Photothermal therapy (PTT) utilizes localized hyperthermia above 50 °C generated by nanomaterials upon exposure to near-infrared (NIR) laser light for effective cancer cell eradication. Yet, in high-temperature PTT, tumor cells develop heat stress tolerance due to elevated heat shock protein (HSP) levels, diminishing therapeutic efficacy. Moreover, excessive heat can trigger inflammatory conditions and promote cancer metastasis. Targeting the glycolytic pathway in highly metabolically active tumor cells offers a promising strategy for inducing starvation therapy, capitalizing on their vigorous energy demands amidst rapid proliferation. Here, we synthesized a highly luminous NIR-II dye, FNF, followed by its encapsulation alongside myricetin (My) within amphiphilic polypeptide carriers through a self-assembly method. The resulting nanoparticles exhibited great NIR-II imaging capabilities and boasted a notable photothermal conversion efficiency of 55.58 %. Furthermore, My effectively impeded glucose transport facilitated by glucose transporter protein 1 (GLUT1), curtailing glucose supply to tumor cells. This interference disrupted mitochondrial energy production, resulting in decreased adenosine triphosphate (ATP) synthesis and subsequent downregulation of HSP70 expression. By leveraging this approach, which targeted HSP expression via GLUT1 inhibition, we enhance the efficacy of PTT while achieving a synergistic effect for mild photothermal therapy through starvation. Statement of significance High expression of heat shock proteins (HSPs) in cancer cells impairs the efficacy of photothermal therapy (PTT) and triggers inflammation or metastasis, among other effects. Rapid malignant proliferation of tumor cells results in high energy metabolism, so interfering with their glucose metabolism to inhibit the glycolytic process is a feasible route for tumor starvation therapy. Here, we employed an amphiphilic polypeptide encapsulated photosensitizer (FNF) and myricetin (My) to construct nanoparticles with both NIR-II imaging capability and high photothermal conversion efficiency (55.58 %). Among them, My blocked glucose transport mediated by glucose transporter protein 1 (GLUT1), reduced the glucose supply and ATP synthesis in cancer cells, and then down regulated HSP70 expression. Thus, this strategy achieves starvation synergistic mild photothermal therapy through metabolic disruption.
研究领域:
生物医学工程
·
肿瘤学
·
纳米医学
✓ 已验证
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2023
·
IF 9.7
Jing-Jie Ye,Peng Bao,Kai Deng,Xue Dong,Jinlian He,Yu Xia,Ziyang Wang,Xinhua Liu,Ying Tang,Jun Feng,Xian-Zheng Zhang
Immune cells distinguish cancer cells mainly relying on their membrane-membrane communication. The major challenge of cancer vaccines exists in difficult identification of cancer neoantigens and poor understanding over immune recognition mechanisms against cancer cells, particularly the combination among multiple antigens and the cooperation between antigens and immune-associated proteins. We exploit cancer cell membranes as the whole cancer antigen repertoire and reinforce its immunogenicity by cellular engineering to modulate the cytomembrane's immune-associated functions. This study reports a vaccine platform based on radiation-engineered cancer cells, of which the membrane HSP70 protein as the immune chaperon/traitor is endogenously upregulated. The resulting positive influences are shown to cover immunogenic steps occurring in antigen-presenting cells, including the uptake and the cross-presentation of the cancer antigens, thus amplifying cancer-specific immunogenicity. Membrane vaccines offer chances to introduce desired metal ions through membrane-metal complexation. Using Mn 2+ ion as the costimulatory interferon genes agonist, immune activity is enhanced to further boost adaptive cancer immunogenicity. Results have evidenced that this artificially engineered membrane vaccine with favorable bio-safety could considerably reduce tumorigenicity and inhibit tumor growth. This study provides a universally applicable and facilely available cancer vaccine platform by artificial engineering of cancer cells to inherit and amplify the natural merits of cancer cell membranes. Statement of significance The major challenge of cancer vaccines exists in difficult identification of cancer neoantigens and poor understanding over immune recognition mechanisms against cancer cells, particularly the combination among multiple antigens and the cooperation between antigens and immune-associated proteins. Cancer cell membrane presents superior advantages as the whole cancer antigen repertoire, including the reported and the unidentified antigens, but its immunogenicity is far from satisfactory. Cellular engineering approaches offer chances to endogenously modulate the immune-associated functions of cell membranes. Such a reinforced vaccine based on the engineered cancer cell membranes matches better the natural immune recognition pathway than the conventional vaccines.
✓ 已验证
DOI
PubMed
高影响因子
MARINE POLLUTION BULLETIN
·
2024
·
IF 5.3
Jiani Liu,Yueyong Shang,Fujing Deng,Zhihua Feng,Menghong Hu,Youji Wang
In the marine environment, nanoparticles play a role in adsorbing and catalytically degrading organic pollutants, thereby mitigating their toxic effects on aquatic organisms. This study aimed to investigate the impact of nano titanium dioxide (nTiO 2 ) and tris (2-chloropropyl) phosphate (TCPP) on the hemolymph and digestive function of the thick-shell mussel Mytilus coruscus . Mussels were divided into a control group, a group exposed to TCPP alone, a group exposed to a combination of TCPP and 0.5 mg/L nTiO 2 , and a group exposed to a combination of TCPP and 1 mg/L nTiO 2 . After 14 days of exposure, oxidative stress responses, including superoxide dismutase (SOD) activity and malondialdehyde (MDA) content, immune defense responses, including acid phosphatase (ACP) and alkaline phosphatase (AKP) activities, and gene expression, including HSP70 expression, were measured in the hemolymph and digestive glands of the mussels. Compared to the control group, mussels solely exposed to 100 μg/L TCPP exhibited a significant reduction in SOD activity in the hemolymph. When TCPP was co-exposed with 0.5 mg/L nTiO 2 , there were significant increases in MDA content and AKP activity in both the digestive gland and hemolymph compared to the control group. Upon co-exposure of TCPP with 1 mg/L nTiO 2 , MDA content and AKP activity in the digestive gland significantly decreased, while SOD, ACP, and AKP activity in the hemolymph significantly increased and MDA content significantly decreased, returning to the control group levels. Furthermore, in the combined exposure, HSP70 gene expression significantly decreased as the nTiO 2 concentration increased from 0.5 mg/L to 1 mg/L. In summary, TCPP impacted the hemolymph and digestive function of mussels, whereas a concentration of 1 mg/L nTiO 2 effectively alleviated the toxic effects of TCPP. This study is crucial for assessing the ecological risks of nanoparticles and emerging organic pollutants in marine environments, and provides new insights into the interaction between nTiO 2 and TCPP, as well as the influence of nTiO 2 concentration on mitigating TCPP toxicity.
研究领域:
海洋生物学
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环境科学
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毒理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nature Communications
·
2023
·Vol. 14
·期 1
·1-25
·
IF 16.6
Li Ting,Jiang Shuhui,Zhang Ying,Luo Jie,Li Ming,Ke Hengte,Deng Yibin,Yang Tao,Sun Xiaohui,Chen Huabing
The survival of malignant tumors is highly dependent on their intrinsic self-defense pathways such as heat shock protein (HSP) during cancer therapy. However, precisely dismantling self-defenses to amplify antitumor potency remains unexplored. Herein, we demonstrate that nanoparticle-mediated transient receptor potential vanilloid member 1 (TRPV1) channel blockade potentiates thermo-immunotherapy via suppressing heat shock factor 1 (HSF1)-mediated dual self-defense pathways. TRPV1 blockade inhibits hyperthermia-induced calcium influx and subsequent nuclear translocation of HSF1, which selectively suppresses stressfully overexpressed HSP70 for enhancing thermotherapeutic efficacy against a variety of primary, metastatic and recurrent tumor models. Particularly, the suppression of HSF1 translocation further restrains the transforming growth factor β (TGFβ) pathway to degrade the tumor stroma, which improves the infiltration of antitumor therapeutics (e.g. anti-PD-L1 antibody) and immune cells into highly fibrotic and immunosuppressive pancreatic cancers. As a result, TRPV1 blockade retrieves thermo-immunotherapy with tumor-eradicable and immune memory effects. The nanoparticle-mediated TRPV1 blockade represents as an effective approach to dismantle self-defenses for potent cancer therapy.
研究领域:
肿瘤学
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免疫疗法
·
纳米技术
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2023
·
IF 5.6
Jing-Mei Lu,Xiang Xu,Fumie Aosai,Ming-Yue Zhang,Lu-Lu Zhou,Lian-Xun Piao
Toxoplasma gondii ( T. gondii )-derived heat shock protein 70 ( T.g. HSP70) is a toxic protein that downregulates host defense responses against T. gondii infection. T.g. HSP70 was proven to induce fatal anaphylaxis in T. gondii infected mice through cytosolic phospholipase A 2 (cPLA 2 ) activated-platelet-activating factor (PAF) production via Toll-like receptor 4 (TLR4)-mediated signaling. In this study, we investigated the effect of arctiin (ARC; a major lignan compound of Fructus arctii ) on allergic liver injury using T.g. HSP70-stimulated murine liver cell line (NCTC 1469) and a mouse model of T. gondii infection. Localized surface plasmon resonance, ELISA, western blotting, co-immunoprecipitation, and immunofluorescence were used to investigate the underlying mechanisms of action of ARC on T. gondii -induced allergic acute liver injury. The results showed that ARC suppressed the T.g. HSP70-induced allergic liver injury in a dose-dependent manner. ARC could directly bind to T.g. HSP70 or TLR4, interfering with the interaction between these two factors, and inhibiting activation of the TLR4/mitogen-activated protein kinase/nuclear factor-kappa B signaling, thereby inhibiting the overproduction of cPLA 2 , PAF, and interferon-γ. This result suggested that ARC ameliorates T.g. HSP70-induced allergic acute liver injury by disrupting the TLR4-mediated activation of inflammatory mediators, providing a theoretical basis for ARC therapy to improve T.g. HSP70-induced allergic liver injury.
研究领域:
免疫学
·
药理学
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寄生虫学
·
肝病学
✓ 已验证
DOI
PubMed
高影响因子
AQUACULTURE
·
2024
·
IF 3.9
Ningbo Wang,Yinan Wang,Rongrong Zhang,Aili Sun,Yin Lu,Zeming Zhang,Xizhi Shi
Triphenylphosphine oxide (TPPO) as a new organophosphorus flame retardant is extensively used in the industrial and pharmaceutical fields due to its chemical stability and abundance. In marine environments, TPPO accumulates as a result of natural ecological processes. This study aimed to evaluate the accumulation process and toxicological effects of TPPO utilizing mussels ( Mytilus coruscus ), a species traditionally employed in marine monitoring and commonly cultivated in offshore aquaculture. GC–MS/MS was employed to quantify the accumulation of TPPO in the gill, gonad, muscle, and digestive gland tissues of mussels exposed to three sublethal concentrations (20.0, 100.0, and 500.0 μg/L) over durations of 3, 7, 14, and 28 days, as well as the examining of the chemical and molecular parameters. Results showed that the accumulation of TPPO (100.0 and 500.0 μg/L) increased throughout the 28 d of exposure, and the peak accumulation of 20.0 μg/L TPPO was detected on 14 d. Short-term TPPO exposure did not cause oxidative stress in mussels. Chronic exposure for 28 days resulted in significant oxidative damage and oxidative stress in mussels, as evidenced by elevated expression and activity of SOD, increased levels of glutathione and malondialdehyde, and upregulation of HSP70 and HSP90, metallothionein, and CYP4Y1, alongside the initiation of apoptotic cell death. TPPO exposure activated natural immune genes and disrupted lipid metabolism in mussels. This study demonstrated the persistent accumulation of TPPO in mussels, highlighting its ecotoxicological hazards and underscoring the necessity to predict the risks associated with widespread environmental exposure to TPPO.
研究领域:
环境科学
·
海洋生物学
·
毒理学
·
生态学
✓ 已验证
产品关联
DOI
高影响因子
POULTRY SCIENCE
·
2021
·
IF 3.352
Chen Yang,Pei Luo,Shi-jian Chen,Zhi-chao Deng,Xin-liang Fu,Dan-ning Xu,Yun-bo Tian,Yun-mao Huang,Wen-jun Liu
ABSTRACT Resveratrol, a natural antioxidant, anti-inflammatory plant extract, was found to have a protective effect in poultry subjected to heat stress. In this study, we strove to characterize resveratrol on intestinal of duck exposed to acute heat stress and investigate the underlying mechanism. A total of 120 Shan-ma ducks (60 days old) were randomly divided into 2 groups. The control group was fed a basal diet, and the resveratrol group was fed a basal diet supplemented with 400 mg/kg resveratrol. Animals in 2 groups were kept at a temperature of 24°C ± 2°C for 15 d. Then, animals of both groups were placed in an artificial climate room at 39°C. Twelve ducks of each group were sacrificed for sampling at 0, 30, and 60 min, respectively. Results indicated that resveratrol increased the ratio of villus height to crypt depth, increased the number of goblet cells, and reduced the histopathological damage of jejunum caused by acute heat stress. Furthermore, the gene expression of heat shock proteins ( HSP60, HSP70 , and HSP90 ) and tight junction proteins ( CLDN1 and OCLN ) was significantly increased in the resveratrol group compared to that in the control groups. Simultaneously, resveratrol significantly activated the SIRT1-NRF1/NRF2 signaling pathways, improved ATP level of jejunum, and increased SOD and CAT antioxidant enzymes activities. In addition, we found that the NF-κB / NLRP3 inflammasome signaling pathways were repressed under acute heat stress. Meanwhile, supplement resveratrol further inhibited the NLRP3 inflammasome pathway, decreased protein level of NLRP3 and caspase1 p20, reduced the secretion of IL-1β. Taken together, our results indicate that resveratrol against the oxidative damage and inflammation injury in duck jejunum induced by heat stress via active SIRT1 signaling pathways.
研究领域:
动物科学
·
营养学
·
生理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF HYPERTHERMIA
·
2015
·
IF 2.645
Jia Ma,Zhiping Zhang,Zhanjie Zhang,Jing Huang,You Qin,Xu Li,Hongli Liu,Kunyu Yang,Gang Wu
Purpose: Heat generated by magnetic nanoparticle clusters (MNCs) in an alternating magnetic field (AMF) can be used for hyperthermia cancer treatment. Here, we have synthesised polyacrylic acid-coated MNCs according to previous report, with the ability to increase particle stability in suspension. Radiosensitisation effects of the MNCs under an AMF were investigated in vitro and in vivo.Materials and methods: MTT assay, flow cytometry, clone formation assay, Western blotting, and a γ-H2AX experiment were used to explore the biocompatibility and radiosensitisation effect of the MNCs and their putative radiosensitisation mechanism. An NCI-H460 mouse xenograft model was used to investigate the anti-tumour effect under an AMF in vivo.Results: The temperature of MNC fluids at different concentrations (200 μg/mL to 2 mg/mL) increased rapidly. The MNCs were endocytosed by the cells and were found to be biocompatible. Hsp70 and caspase-3 were found to be up-regulated upon MNCs under an AMF, radiation, and combination of both treatments. MNCs under an AMF efficiently radiosensitised both CNE-2 cells and NCI-H460 cells. Finally, the tumour inhibition rate after treatment with MNCs under an AMF and radiation was significantly higher than that after either treatment alone. The mechanism of radiosensitisation putatively involves inhibition of DNA repair and induction of apoptosis.Conclusions: The MNC fluids under an AMF enhanced the radiosensitivity of tumour cells both in vitro and in vivo.
研究领域:
肿瘤学
·
纳米技术
·
放射治疗
✓ 已验证
DOI
PubMed
高影响因子
ACS Nano
·
2021
·
IF 15.881
Zhongyuan Chen,Yueting Peng,Yichao Li,Xiaoxue Xie,Xiaodan Wei,Geng Yang,Hanxi Zhang,Ningxi Li,Tingting Li,Xiang Qin,Shun Li,Chunhui Wu,Fengming You,Hong Yang,Yiyao Liu
The combination of magnetic hyperthermia and chemotherapy within a nanosystem is thought to be a promising approach for cancer therapies. However, the nonspecific accumulation and fast clearance of magnetic nanoparticles in the physiological environment limited their further biomedical applications. Herein, we report a highly selective theranostic nanocomplex, ZIPP-Apt:DOX/siHSPs, built with superparamagnetic zinc-doped iron oxide nano-octahedral core, cationic PAMAM dendrimer, and functional surface modifications such as PEG, AS1411 aptamer, and fluorescent tags (FITC or Cy5.5), together with the loading of hydrophobic anticancer drug doxorubicin (DOX) and HSP70/HSP90 siRNAs. Our results demonstrate that the cellular uptake and the tumor-specific accumulation of ZIPP-Apt:DOX/siHSPs were significantly increased due to the AS1411-nucleolin affinity and further confirmed that the simultaneous depletion of HSP70 and HSP90 sensitized magnetic hyperthermia and chemotherapy-induced cell death both in vitro and in vivo. Altogether, our study provides a theranostic nanoplatform for aptamer-targeted, NIR/MR dual-modality imaging guided, and HSP70/HSP90 silencing sensitized magnetochemotherapy, which has the potential to advance versatile magnetic nanosystems toward clinical applications.
研究领域:
纳米技术
·
生物医学工程
·
癌症研究
·
分子生物学
·
药学
·
医学影像
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2024
·
IF 4.5
Jinmei Lai,Qunying Shi,Yongqi Xie,Yinyin Zhu,Shiyu Liang,Yi Chen,Jiali Yuan,Lihan Liu
Tumoral thermal defense mechanisms considerably attenuate the therapeutic outcomes of mild-temperature photothermal therapy (PTT). Thus, developing a simple, efficient, and universal therapeutic strategy to sensitize mild-temperature PTT is desirable. Herein, we report self-delivery nanomedicines ACy NPs comprising a near-infrared (NIR) photothermal agent (Cypate), mitochondrial oxidative phosphorylation inhibitor (ATO), and distearoylphosphatidylethanolamine-polyethylene glycol 2000 (DSPE–PEG2000), which have a high drug-loading efficiency that can reverse tumoral thermal resistance, thereby increasing mild-temperature PTT efficacy. ACy NPs achieved targeted tumor accumulation and performed NIR fluorescence imaging capability in vivo to guide tumor PTT for optimized therapeutic outcomes. The released ATO reduced intracellular ATP levels to downregulate multiple heat shock proteins (including HSP70 and HSP90) before PTT, which reversed the thermal resistance of tumor cells, contributing to the excellent results of mild-temperature PTT in vitro and in vivo. Therefore, this study provides a simple, biosafe, advanced, and universal heat shock protein-blocking strategy for tumor PTT.
研究领域:
纳米技术
·
肿瘤学
·
治疗诊断学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2024
·Vol. 22
·期 1
·1-18
·
IF 10.6
Yin Mingjing,Lei Doudou,Liu Yalan,Qin Tao,Gao Huyang,Lv Wenquan,Liu Qianyue,Qin Lian,Jin Weiqian,Chen Yin,Liang Hao,Wang Bailei,Gao Ming,Zhang Jianfeng,Lu Junyu
Acute lung injury (ALI) is a life threatening disease in critically ill patients, and characterized by excessive reactive oxygen species (ROS) and inflammatory factors levels in the lung. Multiple evidences suggest that nanozyme with diversified catalytic capabilities plays a vital role in this fatal lung injury. At present, we developed a novel class of polydopamine (PDA) coated cerium dioxide (CeO 2 ) nanozyme (Ce@P) that acts as the potent ROS scavenger for scavenging intracellular ROS and suppressing inflammatory responses against ALI. Herein, we aimed to identify that Ce@P combining with NIR irradiation could further strengthen its ROS scavenging capacity. Specifically, NIR triggered Ce@P exhibited the most potent antioxidant and anti-inflammatory behaviors in lipopolysaccharide (LPS) induced macrophages through decreasing the intracellular ROS levels, down-regulating the levels of TNF-α, IL-1β and IL-6, up-regulating the level of antioxidant cytokine (SOD-2), inducing M2 directional polarization (CD206 up-regulation), and increasing the expression level of HSP70. Besides, we performed intravenous (IV) injection of Ce@P in LPS induced ALI rat model, and found that it significantly accumulated in the lung tissue for 6 h after injection. It was also observed that Ce@P + NIR presented the superior behaviors of decreasing lung inflammation, alleviating diffuse alveolar damage, as well as promoting lung tissue repair. All in all, it has developed the strategy of using Ce@P combining with NIR irradiation for the synergistic enhanced treatment of ALI, which can serve as a promising therapeutic strategy for the clinical treatment of ROS derived diseases as well.
研究领域:
纳米技术
·
药学
·
生物医学工程
·
炎症
·
呼吸医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）