CHEMOSPHERE
·
2018
·
IF 4.427
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.
研究领域:
环境毒理学
·
分子生物学
·
心脏病学
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产品关联
DOI
PubMed
高影响因子
BRIEFINGS IN BIOINFORMATICS
·
2021
·Vol. 22
·期 2
·1378-1386
·
IF 11.622
Li Shasha,Liu Wenli,Chen Yangzhen,Wang Liqin,An Wenlin,An Xiaoping,Song Lihua,Tong Yigang,Fan Huahao,Lu Chenyang
Antiviral therapies targeting the pandemic coronavirus disease 2019 (COVID-19) are urgently required. We studied an already-approved botanical drug cepharanthine (CEP) in a cell culture model of GX_P2V, a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related virus. RNA-sequencing results showed the virus perturbed the expression of multiple genes including those associated with cellular stress responses such as endoplasmic reticulum (ER) stress and heat shock factor 1 (HSF1)-mediated heat shock response, of which heat shock response-related genes and pathways were at the core. CEP was potent to reverse most dysregulated genes and pathways in infected cells including ER stress/unfolded protein response and HSF1-mediated heat shock response. Additionally, single-cell transcriptomes also confirmed that genes of cellular stress responses and autophagy pathways were enriched in several peripheral blood mononuclear cells populations from COVID-19 patients. In summary, this study uncovered the transcriptome of a SARS-CoV-2-related coronavirus infection model and anti-viral activities of CEP, providing evidence for CEP as a promising therapeutic option for SARS-CoV-2 infection.
研究领域:
病毒学
·
分子生物学
·
药理学
·
转录组学
·
传染病学
✓ 已验证
DOI
PubMed
高影响因子
CHEMOSPHERE
·
2018
·
IF 4.427
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.
研究领域:
毒理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2025
·
IF 16
Hui Liu,Yanting Yang,Nasha Zhang,Yuebing Hou,Ziqi Zhang,Xinyuan Yu,Yizhou Huang,Bowen Yan,Houren Zhou,Mengyao Mu,Yuan Gao,Kai Guo,Ming Yang,Xiao Sun
The development of new CRISPR/Cas9 delivery systems with a synergistic therapeutic mode can provide a new perspective for efficient tumor treatment. In this work, we developed a bionic 2D FeS nanoplatform with high CRISPR/Cas9 loading (FCRM), highlighting the synergy of CRISPR/Cas9 and ferroptosis in regulating heat shock proteins (HSPs) for enhanced tumor photothermal therapy (PTT). Due to the ultrathin structure and pH-response of FeS nanosheets, FCRM can quickly decompose in a tumor microenvironment and effectively release CRISPR/Cas9 and Fe2+, which can be further enhanced by a photothermal process. CRISPR/Cas9 can accurately downregulate the level of intracellular antiapoptosis protein Survivin. Fe2+ can induce lipid peroxidation and ferroptosis of tumor cells. Ferroptosis and the regulation of Survivin protein can synergistically downregulate the expression of HSPs, thereby reducing the photothermal resistance of tumor cells in PTT. Additionally, FCRM caused significant tumor magnetic resonance contrast enhancement, which aided in the accurate diagnosis of tumors. Therefore, FCRM has great potential in achieving targeted magnetic resonance imaging and dual regulation of HSPs for ferroptosis-gene enhanced tumor PTT.
研究领域:
肿瘤学
·
纳米医学
·
基因编辑
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产品关联
DOI
PubMed
高影响因子
PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY
·
2021
·
IF 3.963
Bao Dong,Xi-Ya Liu,Bin Li,Mao-Ye Li,Shi-Guang Li,Su Liu
Lambda-cyhalothrin (LCT) is a pyrethroid insecticide widely used to control insect pests . Insect exposure to LCT may cause abnormal accumulation of reactive oxygen species (ROS) and result in oxidative damage. Heat shock proteins (HSPs) may help protect against oxidative stress . However, little is known about the role of HSPs in response to LCT in the green peach aphid , Myzus persicae . This insect is an important agricultural pest causing severe yield losses in crops. In this study, we characterized a cDNA sequence ( MpHsp70 ) encoding a member of the HSP70 family in M. persicae . MpHsp70 encoded a 623 amino acid protein putatively localized in the cytosol. The highest expression level of MpHsp70 occurred in fourth-instar nymphs. Treatment of M. persicae with LCT resulted in oxidative stress and significantly increased H 2 O 2 and malondialdehyde levels. This led to an elevated transcription level of MpHsp70 . Injection of H 2 O 2 into M. persicae also upregulated the MpHsp70 expression level, suggesting that MpHsp70 is responsive to ROS, particularly H 2 O 2 , induced by LCT. Recombinant MpHSP70 protein was expressed in Escherichia coli . E. coli cells overexpressing MpHSP70 exhibited significant tolerance to H 2 O 2 and the ROS generators, cumene hydroperoxide and paraquat . This indicated that MpHSP70 protects against oxidative stress. Furthermore, knockdown of MpHsp70 by RNA interference resulted in increased susceptibility in apterous adults of M. persicae to LCT. These findings indicate that MpHsp70 plays an important role in defense against LCT-induced oxidative stress and insecticide susceptibility in M. persicae .
研究领域:
昆虫学
·
分子生物学
·
毒理学
✓ 已验证
DOI
PubMed
高影响因子
Probiotics and Antimicrobial Proteins
·
2019
·Vol. 12
·期 1
·32-38
·
IF 2.962
Zhang Jianming,Han Xue,Zhang Lanwei,Yi Huaxi,Chen Shiwei,Gong Pimin
The effects of fructose on plantaricin Q7 biosynthesis in Lactobacillus plantarum ( L. plantarum ) Q7 were investigated. Fructose induced and accelerated plantaricin Q7 production in the early stages of biosynthesis. Two-dimensional electrophoresis and quantitative real-time reverse transcriptase PCR (qRT-PCR) revealed that shock-related proteins were overexpressed in L. plantarum grown in MRS-fructose compared with cultures grown in MRS broth. A preheat-shock (PHS) treatment was used to overexpress shock-related proteins to enhance plantaricin Q7 production. The final plantaricin Q7 level reached 2873.08 IU/mL following PHS treatment, which was 23.36% higher than that obtained using a control strategy without PHS treatment. qRT-PCR analyses indicated that only groL was induced (by 10-fold) following PHS treatment. Evidently, groL plays a critical role in plantaricin Q7 biosynthesis. These results demonstrate that PHS treatment is an efficient approach to improving plantaricin Q7 production. The information obtained in this study may increase the amount of efficient antimicrobial peptide production using L. plantarum .
研究领域:
微生物学
·
食品科学
✓ 已验证
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2018
·Vol. 7
·期 4
·586-597
·
IF 4.776
Yanan Liu,Meng Xu,Yingyu Zhao,Xu Chen,Xufeng Zhu,Chunfang Wei,Shuang Zhao,Jie Liu,Xiuying Qin
Due to the anti-apoptotic effect employed by cells to protect themselves, recent research shows that photothermal therapy (PTT) can lead to heat shock response, thus reducing the effect of treatment on cancer cells. Small interfering RNA (siRNA), as an effective carrier of RNA interference, can silence the expression of heat shock protein, HSPs or BAG3 genes by inhibiting the expression of specific genes, and thereby inhibiting heat shock response and making cancer cells more sensitive to PTT. In this study, flower-like gold nanoparticles were used as a core for a layer-by-layer strategy to produce a safe and biodegradable nanoparticle platform for gene silencing and photothermal therapy. The results showed that when the mass ratio of the GNFs and siRNA was 20 : 1, the loading efficiency was above 90%, which can effectively silence the expression of BAG3 siRNA. We demonstrated that the GNFs–siRNA still had a good photothermal effect after siRNA modification. In vitro, the GNFs–siRNA showed good biocompatibility and effectively tumor killing properties after laser irradiation. Furthermore, the GNFs–siRNA with laser treatment significantly decreased the expression of BAG3 and remarkably inhibited tumor growth in vivo. This nanosystem establishes an optimized platform for future gene delivery and photothermal therapy.
研究领域:
纳米技术
·
癌症研究
·
治疗学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2024
·
IF 8.3
Yu Dong,Jiaojiao Tao,Bingjie Wang,Aijia Zhang,Guangli Xiang,Shuang Li,Tianze Jiang,Xia Zhao
Photothermal therapy (PTT) shows promise in cancer treatments due to its good spatiotemporal selectivity and minimal invasiveness. However, PTT has some problems such as excessive heat damage to normal tissues, tumor thermo-resistance caused by heat shock proteins (HSPs), and limited efficacy of monotherapy. Here, we construct a patch named “partitioned microneedles” (PMN-SNAP/CuS), which separates the “catalyst” bovine serum albumin-based copper sulfide nanoparticles (CuS@BSA NPs) and the “reactant” S-nitroso-N-acetylpenicillamine (SNAP) into different regions of microneedles, for enhancing mild PTT (mPTT) of melanoma. PMN-SNAP/CuS showed an excellent photothermal effect, Fenton-like catalytic activity, and nitric oxide (NO) generation ability. The combination of NO and reactive oxygen species (ROS) produced by PMN-SNAP/CuS effectively blocked the synthesis of HSPs at the source and enhanced the efficacy of mPTT. Both in vitro and in vivo results proved that PMN-SNAP/CuS significantly enhanced the inhibition of melanoma under 808 nm laser irradiation. In conclusion, our partitioned microneedle strategy based on the combination of enhanced mPTT and gas therapy (GT) provides a promising approach to enhance the therapeutic effect on melanoma.
研究领域:
肿瘤学
·
生物医学工程
·
药剂学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2025
·
IF 5.7
Yan Xiao,Meidong Lang,Xinyue Zheng,Lianlei Wen
Inspired by heat shock proteins (HSPs), thermo-sensitive coacervate-forming polycaprolactone (CPCL) was designed as natural chaperone mimics to protect proteins from thermal stress. Different from coil-globule polymers of poly(N-isopropyl acrylamide) (PNIPAM), the CPCL underwent a partial dehydration during heating, characterized as a coacervate-forming polymer. With the ability to transform between coil and coacervate state in response to temperature, this CPCL could spontaneously capture and release targeted protein, behaving like a natural chaperone of HSPs. Remarkably, compared with the PNIPAM homopolymer, the CPCL provided more efficient protection for proteins by inhibiting heat-induced aggregation above the melting temperature (Tm). Taken together, we envisioned that this CPCL with excellent biodegradability and biocompatibility could be a safe excipient for protein protection against thermal damage without separation.
研究领域:
生物材料学
·
分子生物学
·
生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Toxics
·
2022
·Vol. 10
·期 11
·698
·
IF 4.472
Lina Bai,Peng Shi,Kun Jia,Hua Yin,Jilin Xu,Xiaojun Yan,Kai Liao
Triflumizole (TFZ) toxicity must be investigated in the aquatic environment to understand the potential risks to aquatic species. Accordingly, the adverse effects of TFZ exposure in zebrafish were investigated. Results demonstrate that, after TFZ exposure, the lethal concentration 50 (LC50) in 3 d post-fertilization (dpf) embryos and 6 dpf larvae were 4.872 and 2.580 mg/L, respectively. The development (including pericardium edema, yolk sac retention, and liver degeneration) was apparently affected in 3 dpf embryos. Furthermore, the alanine aminotransferase (ALT) activity, superoxide dismutase (SOD) activity, catalase (CAT) activity, and malondialdehyde (MDA) content in 6 dpf larvae were significantly increased. Additionally, the expression of heat shock response genes (includinghsp70,grp78,hsp90, andgrp94), inflammatory genes (includingp65-nfκb,il-1β, andcox2a), and lipid synthetic genes (includingsrebp1,fas,acc, andppar-γ) in 3 dpf embryos was significantly increased, which was also partially observed in the intestinal cell line formPampus argenteus. Taken together, TFZ could affect the development of zebrafish, accompanied by disturbances of oxidative stress, heat shock response, inflammation, and lipid synthesis. Our findings provide an original insight into the potential risks of TFZ to the aquatic ecosystem.Keywords:triflumizole;zebrafish;oxidative stress;heat shock response;inflammation;lipid synthesis
研究领域:
环境毒理学
·
鱼类生物学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2019
·
IF 8.456
Shaojun Peng,Jiansheng Liu,Yi Qin,Hao Wang,Boling Cao,Ligong Lu,XiangRong Yu
As an oxygen-transporting protein, free hemoglobin (Hb) often suffers from the disadvantage of undesirable stability and short blood circulation, which severely impairs the potential clinical applications as the blood substitute. In this work, Hb was facilely encapsulated into a kind of metal–organic frameworks (MOFs) (ZIF-8) inspired by the natural biomineralization process. The obtained ZIF-8 encapsulating Hb (ZIF-8@Hb) showed the small hydrodynamic size of 180.8 nm and neutral zeta potential of −2.1 mV by adjusting the ratio of Hb in ZIF-8 frameworks. Intriguingly, Hb encapsulated by ZIF-8 exhibited significantly enhanced stability in alkaline, oxidation, high temperature, or enzymatic environment compared with free Hb because of the excellent protective MOF coatings. More importantly, the negative charge of Hb neutralized the original positive charge of ZIF-8, which led to the better biocompatibility, lower protein adsorption, and macrophage uptake of ZIF-8@Hb than bare ZIF-8 nanoparticles. Furthermore, ZIF-8@Hb displayed extended blood circulation with the elimination half-life of 13.9 h as well as reduced nonspecific distribution in normal organs compared with free Hb or ZIF-8 nanoparticles. With the above advantages, ZIF-8@Hb showed significantly extended survival time of mice in a disease model of hemorrhagic shock compared with free Hb or bare ZIF-8 nanoparticles. Overall, this work offers a high-stable and long-circulating oxygen carrier platform, which may find wide applications as a blood substitute to treat various oxygen-relevant diseases.
研究领域:
生物医学工程
·
材料科学
·
临床医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2024
·Vol. 14
·期 30
·21292-21299
·
IF 3.9
Ji Chuan Kong,Feng Zhou,Liting Shi,Yihui Wei,Chunhong Wu
Owing to the complexity of tumor treatment, clinical tumor treatment has evolved from a single treatment mode to multiple combined treatment modes. Reducing the tolerance of tumors to heat and the toxicity of chemotherapy drugs to the body, as well as increasing the sensitivity of tumors to photothermal therapy and chemotherapy drugs, are key issues that urgently need to be addressed in the current cancer treatment. In this work, polylactic acid-based drug nanoparticles (PLA@DOX/GA/ICG) were synthesized with good photothermal conversion ability by encapsulating the water-soluble anticancer drug doxorubicin (DOX), photothermal conversion agent indocyanine green (ICG) and liposoluble drug gambogic acid (GA) using a double emulsion method. The preparation process of PLA@DOX/GA/ICG was examined. Gambogic acid entrapped in PLA@DOX/GA/ICG nanoparticles could act as an HSP90 protein inhibitor to achieve bidirectional sensitization to chemotherapy and photothermal therapy under 808 nm laser irradiation for the first time, effectively ablating breast cancer cells in vitro. This nanodrug was expected to be used for the efficient treatment of tumors.
研究领域:
肿瘤学
·
纳米医学
·
药理学
✓ 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）