TALANTA
·
2017
·
IF 4.162
Yue Hu,Anchen Fu,Zhaoyi Miao,Xiaojing Zhang,Tianlin Wang,An Kang,Jinjun Shan,Dong Zhu,Wei Li
Although ligand fishing has been shown to be an efficient technique for the identification of bioactive components from complex mixtures such as natural products , it cannot be applied to biomedical image processing. Herein, a specific fluorescent ligand fishing combined with in situ imaging approach is presented for the identification of heat shock protein 90 (Hsp 90) inhibitors from complex matrixes, Curcuma longa L. , using N-terminus immobilized Hsp 90α functionalized InP/ZnS quantum dots embedded mesoporous nanoparticles ( i.e. Hsp 90α (NT)-FQDNs) as extraction sorbents and fluorescent tracer. The fished ligands were identified by liquid chromatography time-of-flight/mass spectrometry (LC-TOF/MS) and gas chromatography-mass spectrometry (GC-MS). Moreover, in situ imaging by confocal laser scanning microscopy (CLSM) was applied for evaluating the effect of fished-ligands on bioactivity-induced apoptosis morphologically in HeLa cells. MTT assay verified the bioactivity of the ligands and molecular docking results further provided convincing information to verify the feasible binding mode between ligands and protein. Twelve ligands as potential Hsp 90 inhibitors were ultimately fished and identified from Curcuma longa L. crude extracts. The proposed approach based on Hsp 90α functionalized nanocomposites is superior in the combination of highly specific screening efficiency and concurrent visual in situ imaging, which could have great promise for the development of other plant-derived Hsp 90 inhibitors, and providing a rapid and reliable platform for discovering biologically active molecules in natural products.
研究领域:
药理学
·
生物化学
·
分子生物学
·
纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Materials Today Bio
·
2025
·
IF 10.2
Zhenying Diao,Youcheng Liang,Yong Liu,Dou Zhang,Long Qiu,Jianbo Sun,Qiaoyou Lu,Yanlei Liu,Daxiang Cui,Ting Yin
Blockade of heat shock protein 90 (HSP90) expression in multimodal synergistic therapy has a great prospect for cancer treatment. Nanomaterials combined with bioinformatic analysis provides accurate guidance for the design of anti-HSP90 nanomedicines. Herein, a NIR-II-responsive nanoplatform was developed under bioinformatics guided to effectly inhibit HSP90 for enhanced synergistic mild-photothermal chemotherapy without any notable tissue damage. The nanoplatforms were assembled from NIR-II-responsive gold nanobipyramids (GNBs) combined with curcumin (Cur) via hydrophobic-hydrophobic interactions and hydrogen bonds. On the basis of drug discovery and network pharmacology, we found that Cur has impressive anti-HSP90 capability and analyzed its therapeutic mechanism against NSCLC. Under the irradiation of NIR-II light, the obtained GNBs-Cur blocked the expression of HPS90 and inhibited related antiapoptotic pathways, thus enhancing the mild PTT of GNBs under 1064 nm laser irradiation. Meanwhile, Cur served as chemotherapeutic agents to induce apoptosis in tumor cells. In vivo photoacoustic imaging-guided, GNBs-Cur achieved effective tumor elimination through mild-photothermal chemotherapy without systemic toxicity. Overall, this work provides a new therapeutic modality paradigm for potential NSCLC treatment on the basis of synergistic therapies.
研究领域:
癌症治疗
·
纳米技术
·
药理学
·
生物信息学
·
医学成像
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CHEMICAL THERMODYNAMICS
·
2023
·
IF 2.6
Zhenghui Li,Ziwen Dong,Huijun He,Ganbing Yao,Renjie Xu
The equilibrium solubility of sulfenone in various aqueous cosolvent systems was determined by isothermal saturation method at 278.15–323.15 K under 101.2 kPa. Four cosolvents (methanol, ethanol, isopropanol and n -propanol) exhibited different power in dissolving. The specific performance was that in the saturated state, the content of sulfenone in n -propanol + water was the most and in methanol + water was the least. The Jouyban-Acree (J-A), van’t Hoff-Jouyban-Acree (V-J-A) and Apelblat-Jouyban-Acree (A-J-A) models were utilized to correlate the obtained solubility data of sulfenone. The maximum of relative average deviation ( RAD ) and root-mean-square deviation ( RMSD ) were 1.47 × 10 −2 (from A-J-A) and 6.07 × 10 −5 (from V-J-A). In addition, the difference in dissolution was explained from a microscopic point of view through the acquisition of hansen solubility parameters (HSPs). The preferential solvation parameter δx 1,3 was calculated by Inverse Kirkwood-Buff Integrals (IKBI) method, the change trend of δx 1,3 presented in the entire concentration range was non-linear. The apparent thermodynamic parameters were calculated by van’t Hoff plots and the results indicated that the dissolution process of sulfenone is an endothermic and entropy increment process.
研究领域:
化学
·
物理化学
✓ 已验证
DOI
高影响因子
JOURNAL OF MOLECULAR LIQUIDS
·
2020
·
IF 5.065
Yi Yu,Fanfan Li,Shanghai Long,Li Xu,Guoji Liu
Due to the lack of solubility data and thermodynamic parameters of vitamin K 3 in literature, we determined the solubility of vitamin K 3 in ten organic solvents including 1,2-dichloroethane, acetone, dichloromethane , cyclohexane , methanol, acetonitrile , methyl acetate , i-propanol, n-propanol and n-butanol in this research. It was found that the solubility of vitamin K 3 increases with the increasing temperature ranging from 278.15 to 313.15 K in all ten solvents. Four thermodynamic models regression illustrate that modified Apelblat is the most appropriate model to describe solubility of vitamin K 3 in these ten solvents; it provides 100 RAD value of 1.48 as well as 10 4 RMSD value of 5.94. To explain the change patterns of vitamin K 3 solubility in ten solvents, Hansen solubility parameters and DFT calculation were both applied. Outcomes indicate the solubility laws of vitamin K 3 not only depend on polarity and hydrogen bonded parameters but also rely on intermolecular interactions . On account of these, 1,2-dichloroethane and dichloromethane with stronger solute-solvent interactions show greater solubility than other solvents. Thermodynamic studies reveal that the dissolution of vitamin K 3 in these ten solvents is an entropy-driven and endothermic process.
研究领域:
药学
·
物理化学
✓ 已验证
产品关联
DOI
高影响因子
Antioxidants
·
2021
·Vol. 10
·期 6
·930
·
IF 6.313
Nan Zhang,Shunshan Jiao,Pu Jing
Many studies have demonstrated that cabbages possess various biological activities, and our previous studies confirmed that cyanidin-3-diglucoside-5-glucoside (CY3D5G), the major core of red cabbage anthocyanins, exhibited in vitro antioxidant activity. This study further investigated the protective effects of CY3D5G derivative from red cabbage juice (RCJ) on oxidative stress and lifespan in cells andCaenorhabditis elegans, green cabbage juice (GCJ) was used as control. RCJ rather than GCJ significantly improved cell viability and decreased lactate dehydrogenase release in H2O2-induced caco-2 cells. RCJ significantly increased survival during oxidative and heat stress and mean lifespan inC. elegansby 171.63% and 31.64%, and 28.16%, respectively, while GCJ treatment showed no significant effects (p< 0.05). These results might be attributed to significantly (p< 0.05) higher contents of total phenolics, ascorbic acid, glucosinolates, and anthocyanins in RCJ compared to those in GCJ. Additionally, both of them decreased autofluorescence and reproductive capacity, increased body length, but did not alter the intracellular ROS level. Prolonged lifespan by RCJ might require heat-shock transcription factor pathway, sirtuin signaling, and calmodulin kinase II pathway, independent of insulin/insulin-like growth factor-1 signaling pathway. RCJ showed promising antioxidant properties in caco-2 cells andC. elegans, which provided more information on the health benefits of cabbage.Keywords:lifespan;anthocyanins;phytochemicals;HSP-1 pathway;CaMKII pathway;HSP-1 pathway;caco-2 cells
研究领域:
营养学
·
生物化学
·
分子生物学
·
老年学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Pharmaceutica Sinica B
·
2018
·
IF 6.014
Xichuan Tang,Liwei Tan,Kun Shi,Jinrong Peng,Yao Xiao,Wenting Li,Lijuan Chen,Qian Yang,Zhiyong Qian
Enhancing the heat-sensitivity of tumor cells provides an alternative solution to maintaining the therapeutic outcome of photothermal therapy (PTT). In this study, we constructed a therapeutic system, which was composed of methoxy-polyethylene-glycol-coated-gold-nanorods (MPEG-AuNR) and VER-155008-micelles, to evaluate the effect of VER-155008 on the sensitivity of tumor cells to heat, and further investigate the therapeutic outcome of MPEG-AuNR mediated PTT combined with VER-155008- micelles. VER-155008- micelles down-regulate the expression of heat shock proteins and attenuate the heat-resistance of tumor cell. The survival of HCT116 cells treated with VER-155008- micelles under 45 °C is equal to that treated with high temperature hyperthermia (55 °C) in vitro . Furthermore, we proved either the MPEG-AuNR or VER-155008- micelles can be accumulate in the tumor site by photoacoustic imaging and fluorescent imaging. In vivo anti-cancer evaluation showed that tumor size remarkably decreased (smaller than 100 mm 3 or vanished) when treated with combing 45 °C mild PTT system, which contrasted to the tumor size when treated with individual 45 °C mild PTT (around 500 nm 3 ) or normal saline as control (larger than 2000 nm 3 ). These results proved that the VER-155008- micelles can attenuate the heat-resistance of tumor cells and enhance the therapeutic outcome of mild-temperature photothermal therapy.
研究领域:
纳米技术
·
癌症治疗
·
药学
·
生物医学工程
✓ 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
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2024
·Vol. 25
·期 23
·13148
·
IF 4.9
Run-Jia Wang,Ya-Jing Ni,Yan-Qiang Liu
Hesperetin (Hst) is a common citrus fruit flavonoid with antioxidant, anti-inflammatory, and anti-neurodegenerative effects. To explore the antioxidant and anti-aging effects and mechanisms of Hst, we induced chronic oxidative stress in Caenorhabditis elegans (C. elegans) using low-concentration H 2 O 2 and examined its effects on lifespan, healthy life index, reactive oxygen species (ROS), antioxidant enzymes, and transcriptomic metrics. Hst significantly prolonged lifespan, increased body bending and pharyngeal pumping frequency, decreased ROS accumulation, and increased antioxidant enzyme activity in normal and stressed C. elegans . Hst significantly upregulated daf-18 , daf-16 , gst-2 , gst-3 , gst-4 , gst-39 , hsp-16.11 , sip-1 , clpp-1 , and dve-1 and downregulated ist-1 and kgb-1 mRNAs in stressed C. elegans . These genes are involved in the insulin/insulin-like growth factor-1 signaling (IIS), heat shock protein (HSP), mitochondrial unfolded protein response (mtUPR), and c-Jun N-terminal kinase (JNK) pathways. In summary, Hst increases lifespan and antioxidant ability, correlating with these pathways, during chronic oxidative stress in C. elegans .
研究领域:
分子生物学
·
遗传学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Bio Materials
·
2022
·
IF 0
Mengying Li,Ning Li,Junjie Qi,Dong Gao,Mei Zhou,Xiao Wei,Chengfen Xing
Mild-temperature photothermal therapy (PTT) is being extensively explored because it causes less injury to normal cells. However, the effect of mild-temperature PTT is decreased because of heat shock protein (HSP) overexpression. To solve this problem, we designed functional conjugated polymer nanoparticles (CPNs-G) that enhance the mild-temperature photothermal effect. Upon near-infrared (NIR) light irradiation, CPNs-G generate local heat to realize the photothermal effect. Meanwhile, the increased temperature enhances the catalytic activity of GOx, thus impeding the generation of adenosine triphosphate (ATP) and inhibiting HSP expression. Therefore, this work provides a strategy for overcoming thermoresistance through an enzyme-mediated starvation effect regulated by NIR light.
研究领域:
生物医学工程
·
纳米技术
·
癌症治疗
·
光热疗法
✓ 已验证
DOI
PubMed
Antioxidants
·
2023
·Vol. 12
·期 1
·125
·
IF 7
Sai-Ya Zhang,Zi-Chen Qin,Yi-Yang Sun,Yu-Si Chen,Wen-Bo Chen,Hong-Gang Wang,Di An,Dan Sun,Yan-Qiang Liu
To determine the anti-heat stress and antioxidant effects of genistein and the underlying mechanisms, lipofuscin, reactive oxygen species (ROS), and survival under stress were first detected inCaenorhabditis elegans (C. elegans); then the localization and quantification of the fluorescent protein was determined by detecting the fluorescently labeled protein mutant strain; in addition, the aging-related mRNAs were detected by applying real-time fluorescent quantitative PCR inC. elegans. The results indicate that genistein substantially extended the lifespan ofC. elegansunder oxidative stress and heat conditions; and remarkably reduced the accumulation of lipofuscin inC. elegansunder hydrogen peroxide (H2O2) and 35 °C stress conditions; in addition, it reduced the generation of ROS caused by H2O2and upregulated the expression ofdaf-16,ctl-1,hsf-1,hsp-16.2,sip-1,sek-1,pmk-1, andeat-2, whereas it downregulated the expression ofage-1anddaf-2inC. elegans;similarly, it upregulated the expression ofdaf-16,sod-3,ctl-1,hsf-1,hsp-16.2,sip-1,sek-1,pmk-1,jnk-1 skn-1, andeat-2, whereas it downregulated the expression ofage-1,daf-2,gst-4, andhsp-12.6inC. elegansat 35 °C; moreover, it increased the accumulation of HSP-16.2 and SKN-1 proteins in nematodes under 35 °C and H2O2conditions; however, it failed to prolong the survival time in the deleted mutant MQ130 nematodes under 35 °C and H2O2conditions. These results suggest that genistein promote anti-heat stress and antioxidant effects inC. elegansvia insulin/-insulin-like growth factor signaling (IIS), heat shock protein (HSP), mitogen-activated protein kinase (MAPK), dietary restriction (DR), and mitochondrial pathways.Keywords:genistein;anti-heat stress;antioxidant;Caenorhabditis elegans
研究领域:
分子生物学
·
老年医学
·
遗传学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2023
·
IF 8
Yan Zhou,Zekun Zhou,Xiaojuan Wu,Zefeng Wang,Wangdan Qi,Jing Yang,Liming Qing,Juyu Tang,Le Deng
Purpose We aimed to develop an oxidative-stress-activated palladium-copper nanozyme to reduce bacterial’s heat sensitivity by down-regulating heat shock proteins to overcome the shortcomings of conventional photothermal antimicrobial therapy and achieve mild photothermal bactericidal efficacy.Methods We first synthesized palladium-copper nanozymes (PC-NPs) by hydration and used transmission electron microscopy, X-ray diffraction, and Fourier transform infrared spectroscopy to demonstrate their successful preparation. Their photothermal therapy (PTT) and chemo-dynamic therapy (CDT) activities were then determined by a series of photothermal performance tests and peroxidase-like performance tests, and the destruction of heat shock proteins by reactive oxygen species (ROS) was verified at the protein level by Western Blotting tests, providing a basis for the effective bacteria-killing by the mild-temperature photothermal treatment subsequently applied. We also validated this promising programmed and controlled antimicrobial treatment with palladium-copper nanozymes by in vivo/in vitro antimicrobial assays. A hemolysis assay, MTT cytotoxicity test and histopathological analysis were also performed to assess the in vivo safety of PC-NPs.Results In the micro-acidic environment of bacterial infection, PC-NPs showed peroxidase-like activity that broke down the H2O2 at the wound into hydroxyl radicals and down-regulated bacterial heat shock proteins. The application of PC-NPs increased bacteria’s sensitivity to subsequent photothermal treatment, enabling the elimination of bacteria via mild photothermal treatment.Conclusion The programmed synergistic catalytic enhancement of CDT and mild photothermal therapy achieves the most efficient killing of bacteria and their biofilms, which brings future thinking in the relationship between heat shock proteins and oxidative stress damage in bacteria.
研究领域:
纳米技术
·
生物医学工程
·
微生物学
·
药学
·
治疗学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL SCIENCES
·
2021
·
IF 3.534
Shanshan Li,Long Zhang,Mingda Li,Jiao Huang,Baocheng Cui,Jie Jia,Zhaoming Guo,Kun Ma,Changhao Cui
B lymphoblastic leukemia (B-LL) is a clonal hematopoietic stem cell neoplasm derived from B-cell progenitors, which mainly occurs in children and adolescents and is one of the main causes of death from malignant tumors in this population. The surface marker CD19 is specifically expressed on the membrane of most malignant B-cells, which is widely used as a marker of B-LL antigen-specific immunotherapy . In this study, mesoporous titanium dioxide nanoparticles (MTNs)-based antibody drug delivery system was designed for B-LL treatment. Anti-CD19 monoclonal antibody was conjugated to PEGylated MTNs, and doxorubicin (DOX) was loaded in the nanoparticle . The CD19-PEG-MTN/DOX nanoparticle could recognize CD19 + B -LL cell lines and induced them apoptosis, but nontoxic for the normal cells. Further, after treated with CD19-PEG-MTN/DOX nanoparticle, pro-apoptotic proteins Bax and Caspase-3 in KOPN 8 and NALM-6 cells were significantly upregulated, but anti-apoptotic proteins Bcl2 , MCL-1, HSP 70, and BAG 3 were downregulated, which indicated the activation of the apoptosis pathway by the nanodrug. By contrast, CD19-PEG-MTN/DOX didn't play a part on CD19 − cell line U937. Besides, the cytotoxicity of CD19-PEG-MTN/DOX was low with good biocompatibility. Collectively, CD19-PEG-MTN/DOX is a promising antitumor nanodrug for the treatment of B-LL.
研究领域:
肿瘤学
·
纳米技术
·
药学
·
免疫疗法
✓ 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）