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HSPs
CHEMOSPHERE · 2018 · IF 4.427

Di (2-ethyl hexyl) phthalate (DEHP)-induced kidney injury in quail (Coturnix japonica) via inhibiting HSF1/HSF3-dependent heat shock response

Peng-Cheng Li,Xue-Nan Li,Zheng-Hai Du,Hui Wang,Zhuo-Ran Yu,Jin-Long Li

Di (2-ethyl hexyl) phthalate (DEHP) as a plasticizer can leach away from the plastic and hence entrances into the animal food chain which caused serious hazard in organs of animals, but there are few studies on DEHP kidney toxicity. The heat-shock response (HSR) consisting of the HSPs and HSFs plays an important role in various toxicity stress conditions. To investigate the influence on kidney toxicity and the modulation of HSR during DEHP exposure, female quail were fed the diet with 0, 250, 500 and 750 mg/kg DEHP by gavage administration for 45 days. The shrinkages of glomeruli and dilation of kidney tubule epithelia cells were observed in the kidney of DEHP-exposed quail. DEHP treatment could significantly decrease the expressions of HSP25, HSP27, HSP47, HSP60 , while the expressions of HSP10, HSP40, HSP70, HSP90, HSP110 were upregulated in the kidney. In addition, the expression levels of HSF1 and HSF3 were significantly increased under DEHP. This is the first study to demonstrate quail exposure to DEHP is in fact detrimental to bird kidney. Besides, DEHP could attack HSR by affecting the synthesis of HSFs to mediate the transcription of the HSPs resulting in kidney damage.

CAS / MDL: 117-81-7
研究领域: 毒理学 · 分子生物学
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Small · 2025 · IF 12.1

Multifunctional Nanoparticles Inhibit HSPs Expression and Improve Pyroptosis Through ROS Amplification in Mild Photothermal Therapy of Oral Squamous Cell Carcinoma

Xu Zhang,Zhichao Dou,Huayang Fan,Tu Huang,Zhuohao Zhang,Yaling Tang,Xin-hua Liang

Reactive oxygen species (ROS) can catalyze the palmitoylation of Gasdermin D (GSDMD), thereby promoting pyroptosis. However, tumor cells frequently exhibit elevated expression of heat shock proteins (HSPs), which attenuate pyroptosis through the inhibition of key pyroptotic mediators. To solve these problems, a folate-acid-modified polydopamine nanoparticle loaded with copper peroxide (PDCF nanoparticles) is developed to simultaneously trigger and amplify pyroptosis while suppressing HSPs-mediated defensive mechanisms. PDCF nanoparticles efficiently elevated intracellular ROS, thereby directly promoting the palmitoylation and subsequent cleavage of GSDMD to its active N-terminal GSDMD (GSDMD-N). This process created a positive feedback loop that enhanced pyroptosis, characterized by pore formation in the plasma membrane and the release of interleukin 1β (IL-1β) and interleukin 18 (IL-18). Concurrently, the elevated ROS significantly downregulated HSPs expression to achieve a mild photothermal therapy (MPTT). This combined strategy of pyroptosis amplification and HSPs inhibition potently suppressed tumor growth in oral squamous cell carcinoma (OSCC). The novel multifunctional therapeutic strategy provides a new view for the treatment of OSCC through ROS-mediated downregulation of HSPs and improving pyroptosis.

研究领域: 纳米医学 · 癌症治疗 · 光热治疗 · 分子生物学 · 肿瘤学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Acta Biomaterialia · 2023 · IF 9.7

Small-size Ti3C2Tx MXene nanosheets coated with metal-polyphenol nanodots for enhanced cancer photothermal therapy and anti-inflammation

Tao Liao,Zhongyin Chen,Ying Kuang,Zhe Ren,Wenqian Yu,Wen Rao,Linwei Li,Yun Liu,Ziqiang Xu,Bingbing Jiang,Cao Li

As a controllable, simple method with few side effects, near-infrared (NIR) light-based photothermal therapy (PTT) has been proven an effective cancer therapeutic approach. However, PTT-induced inflammation is a potential negative factor. And the overexpressed heat shock proteins (HSPs) by cancer cells can protect them from hyperthermia during PTT. In this work, small-size Ti 3 C 2 T x MXene nanosheets with high photothermal conversion efficiency in the region of NIR, high cargo loading capability and good free radical scavenging capability were chosen for cancer PTT and anti-inflammation. And (-)-epigallocatechin gallate (EGCG) was applied to form EGCG/Fe metal-polyphenol nanodots on the nanosheets. EGCG being released in acid cancer cells could reduce the expression of HSPs and could be used for anti-inflammation. As a result, the complex nanosheets named MXene@EGCG could achieve enhanced cancer PTT and be anti-inflammatory. Both in vitro and in vivo studies proved the good photothermal ability of MXene@EGCG and demonstrated that it could inhibit the expression of HSPs in tumor cells and relieve PTT-induced inflammation. Therefore, the nanosheets show good results in tumor ablation with a low level of inflammation, which provides another possibility for cancer therapy. Statement of significance Photothermal therapy (PTT)-induced inflammation plays an essential role in some important stages of tumor development and is unfavorable for cancer treatment. And hyperthermia leads to the overexpression of heat shock proteins (HSPs) in cancer cells, which limits the therapeutic effect of PTT. Therefore, we coated small-size Ti 3 C 2 T x MXene nanosheets with (-)-epigallocatechin gallate (EGCG)/Fe metal-polyphenol nanodots and named them as MXene@EGCG. This system shows a good photothermal conversion efficiency at 808 nm. And it can release EGCG in cancer cells to inhibit the expression of HSPs, thus achieving an enhanced cancer PTT. Both MXene and EGCG can also diminish the PTT-trigged inflammation. Both in vitro and in vivo studies prove the good anti-cancer PTT effect and anti-inflammation capability of MXene@EGCG.

CAS / MDL: 989-51-5
研究领域: 生物医学工程 · 纳米技术 · 癌症治疗 · 药学
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CHEMOSPHERE · 2018 · IF 4.427

Modulation of heat-shock response is associated with Di (2-ethylhexyl) phthalate (DEHP)-induced cardiotoxicity in quail (Coturnix japonica)

Hui Wang,Xue-Nan Li,Peng-Cheng Li,Wei Liu,Zheng-Hai Du,Jin-Long Li

Di(2-ethylhexyl) phthalate (DEHP) is an omnipresent environmental pollutant with endocrine disrupting properties. As a plasticizer , DEHP can be leach from the plastic to transfer the external environment and thus enters the animal food chain, causing serious damage to the animal organs. The heat-shock response (HSR) comprising heat-shock protein (HSPs) and heat-shock transcription factor (HSFs) plays a pivotal role in various toxic stress conditions. For the sake of investigating the effects of DEHP exposure on cardiac toxicity and the regulation of HSR, male quail were fed the diet with 0, 250, 500 and 750 mg/kg DEHP by gavage administration for 45 days. Histopathological changes including cardiomyocyte swelling and muscle fiber dilatation were observed in the hearts exposed to DEHP. During the DEHP treatment, the mRNA expression of HSP60 and HSP70 were universally reduced, while the expression of other HSPs ( HSP10, HSP25, HSP27, HSP40, HSP47, HSP90, HSP110 ) had different degrees of growth. In addition, the levels of HSF1, HSF2, and HSF3 were significantly increased. Given the facts above, DEHP exposure induced the toxic effects of quail heart. DEHP exposure did great harm to HSR via affecting the synthesis of HSFs to mediate the transcription of the HSPs. Ultimately, this study provided new evidence that DEHP-induced cardiotoxicity in quail was related to activation of HSR and playing a protective role.

CAS / MDL: 117-81-7
研究领域: 环境毒理学 · 分子生物学 · 心脏病学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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BIOMATERIALS · 2021 · IF 12.479

NIR-II fluorescence imaging guided tumor-specific NIR-II photothermal therapy enhanced by starvation mediated thermal sensitization strategy

Yeneng Dai,Zhiquan Sun,Honghai Zhao,Dashan Qi,Xiangyu Li,Diya Gao,Meixing Li,Quli Fan,Qingming Shen,Wei Huang

Photothermal therapy (PTT) is hampered by limited light penetration depth and cell thermoresistance induced by over-expressed heat shock proteins (HSPs). Herein, we proposed a tumor-specific enhanced NIR-II PTT through the starvation mediated thermal sensitization strategy. A semiconducting polymer with superior NIR-II fluorescence imaging (FI) performance and NIR-II PTT efficacy was synthesized and encapsulated into folate modified liposomes , together with a glycolysis inhibitor, 2-deoxy- d -glucose (2DG). Upon specifically targeting folate receptors and guidance of NIR-II FI, spatiotemporal 2DG release could be achieved by the trigger of NIR-II photothermal effect. The released 2DG could not only deplete the energy supply of tumor cells by inhibiting tumor anaerobic glycolysis , but also decrease the ATP levels and hamper the production of HSPs, ultimately enhancing the tumor thermal sensitivity toward PTT. Owing to the sensitization effect of 2DG, tumor cells with overexpressed folate receptors could be significantly damaged by NIR-II PTT with an enhanced therapeutic efficiency. The work provided a promising strategy for specific starvation/NIR-II PTT synergistic therapy towards tumors.

CAS / MDL: 154-17-6 298-93-1
研究领域: 癌症治疗 · 生物医学工程 · 纳米技术 · 分子生物学
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ADVANCED FUNCTIONAL MATERIALS · 2020 ·Vol. 30 ·期 14 ·1909806 · IF 16.836

Self-Mineralized Photothermal Bacteria Hybridizing with Mitochondria-Targeted Metal–Organic Frameworks for Augmenting Photothermal Tumor Therapy

Qi-Wen Chen,Xin-Hua Liu,Jin-Xuan Fan,Si-Yuan Peng,Jia-Wei Wang,Xia-Nan Wang,Cheng Zhang,Chuan-Jun Liu,Xian-Zheng Zhang

A photothermal bacterium (PTB) is reported for tumor-targeted photothermal therapy (PTT) by using facultative anaerobic bacterium Shewanella oneidensis MR-1 ( S. oneidensis MR-1) to biomineralize palladium nanoparticles (Pd NPs) on its surface without affecting bacterial activity. It is found that PTB possesses superior photothermal property in near infrared (NIR) regions, as well as preferential tumor-targeting capacity. Zeolitic imidazole frameworks-90 (ZIF-90) encapsulating photosensitizer methylene blue (MB) are hybridized on the surface of living PTB to further enhance PTT efficacy. MB-encapsulated ZIF-90 (ZIF-90/MB) can selectively release MB at mitochondria and cause mitochondrial dysfunction by producing singlet oxygen ( 1 O 2 ) under light illumination. Mitochondrial dysfunction further contributes to adenosine triphosphate (ATP) synthesis inhibition and heat shock proteins (HSPs) down-regulated expression. The PTB-based therapeutic platform of PTB@ZIF-90/MB demonstrated here will find great potential to overcome the challenges of tumor targeting and tumor heat tolerance in PTT.

CAS / MDL: 141-53-7
研究领域: 癌症治疗 · 纳米技术 · 生物医学工程 · 光疗
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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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Frontiers in Microbiology · 2024 · IF 4

Mechanisms underlying the low-temperature adaptation of 17β-estradiol-degrading bacterial strain Rhodococcus sp. RCBS9: insights from physiological and transcriptomic analyses

Qiannan Li,Hanyu Pan,Peng Hao,Zhenhua Ma,Xiaojun Liang,Lianyu Yang,Yunhang Gao

The 17β-estradiol (E2)-degrading bacterium Rhodococcus sp.RCBS9 previously showed remarkable resistance to the combined stresses of low temperature and E2. In this study, physiological experiments and transcriptomic analysis were performed to investigate the mechanisms underlying the strain's low-temperature adaptation and briefly analyze how it maintains its ability to degrade E2 at low temperature. The results showed that the strain's signal transduction functions, adaptive changes in cell membrane and cell wall structure, gene repair functions, and synthesis of antioxidants and compatible solutes are key to its ability to adapt to low temperature. In addition, its stress proteins in response to low temperature were not typical cold shock proteins, but rather universal stress proteins (USPs) and heat shock proteins (HSPs), among others. The strain also upregulated biofilm production, transporter proteins for carbon source uptake, and proteins for fatty acid degradation to ensure energy generation. The strain's multiple stress responses work synergistically to resist low-temperature stress, ensuring its adaptability to low-temperature environments and ability to degrade E2. Finally, six genes related to survival at low temperature (identified in the transcriptome analysis) were expressed in E. coli BL21, and they were found to contribute to recombinant E. coli growth at low temperature.

CAS / MDL: 548-62-9
研究领域: 微生物学 · 环境科学 · 分子生物学 · 基因组学
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CHEMICAL ENGINEERING JOURNAL · 2021 · IF 13.273

Remotely-activatable extracellular matrix-mimetic hydrogel promotes physiological bone mineralization for enhanced cranial defect healing

Lu Tan,Yan Hu,Menghuan Li,Yuchen Zhang,Chencheng Xue,Maohua Chen,Zhong Luo,Kaiyong Cai

The biomineralization of calcium ions and phosphate ions in the extracellular matrix (ECM) is a key event in bone regeneration, and it’s of therapeutic significance to develop biomaterials capable of mimicking the physiological biomineralization process, which is especially desirable in cranial defect repairing. For this purpose, we design a composite remotely-activatable ECM-mimetic chitosan/collagen-based hydrogel incorporated with mesenchymal stem cell (MSC)-membrane-coated black phosphorus (BP), which is a photothermal material with versatile utility. Here, the MSC membrane-coated BP nanosheets could induce mild photothermal effect under near-infrared (NIR) light to stimulate the osteoblast recruitment via activating the heat shock proteins (HSPs)-mediated matrix metalloproteinase (MMP) and ERK-Wnt/β-catenin-RUNX2 axis. Meanwhile, the thermal decomposition of BP would release phosphate ions into the surrounding medium to attract calcium ions to form hydroxyapatite in the ECM in an in-situ manner, which is beneficial for osteoblast migration and osteogenic differentiation. After the implantation in to the cranial defect site on Sprague Dawley (SD) rats, it was evidently observed that the hydrogel treatment substantially enhanced the local bone density and promoted new bone formation. Overall, the ECM-mimetic BP-incorporated hydrogel could enhance osteoblast migration/differentiation and stimulate the biomineralization process under remote NIR activation to promote bone healing, which offers new opportunities for repairing cranial defect in the clinics.

CAS / MDL: 9012-76-4 6902-77-8
研究领域: 生物材料 · 组织工程 · 骨再生 · 光热疗法 · 生物医学工程
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