NUCLEIC ACIDS RESEARCH
·
2018
·Vol. 46
·期 7
·3284-3297
·
IF 11.561
Tong Qingyi,You Huijuan,Chen Xintao,Wang Kongchao,Sun Weiguang,Pei Yufeng,Zhao Xiaodan,Yuan Ming,Zhu Hucheng,Luo Zengwei,Zhang Yonghui
Despite All-trans retinoic acid (ATRA) has transformed acute promyelocytic leukemia (APL) from the most fatal to the most curable hematological cancer, there remains a clinical challenge that many high-risk APL patients who fail to achieve a complete molecular remission or relapse and become resistant to ATRA. Herein, we report that 5-(4-methoxyphenethyl)-[1, 3] dioxolo [4, 5-j] phenanthridin-6(5H)–one (ZYH005) exhibits specific anticancer effects on APL and ATRA-resistant APL in vitro and vivo, while shows negligible cytotoxic effect on non-cancerous cell lines and peripheral blood mononuclear cells from healthy donors. Using single-molecule magnetic tweezers and molecule docking, we demonstrate that ZYH005 is a DNA intercalator. Further mechanistic studies show that ZYH005 triggers DNA damage, and caspase-dependent degradation of the PML-RARa fusion protein. As a result, APL and ATRA-resistant APL cells underwent apoptosis upon ZYH005 treatment and this apoptosis-inducing effect is even stronger than that of arsenic trioxide and anticancer agents including 5-fluorouracil, cisplatin and doxorubicin. Moreover, ZYH005 represses leukemia development in vivo and prolongs the survival of both APL and ATRA-resistant APL mice. To our knowledge, ZYH005 is the first synthetic phenanthridinone derivative, which functions as a DNA intercalator and can serve as a potential candidate drug for APL, particularly for ATRA-resistant APL.
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DOI
PubMed
高影响因子
FOOD HYDROCOLLOIDS
·
2018
·
IF 5.089
Hao Cheng,Zheng Fang,Wusigale,Amr M. Bakry,Yantao Chen,Li Liang
Clarification of the mechanism of protein-ligand interaction is important for the encapsulation of bioactive components. Trans -resveratrol is labile to convert to cis -isomer during fermentation and storage, but the cis -isomer interaction with proteins has not yet gained as much attention as that of trans -isomer. The influence of resveratrol's isomerization on interaction with ligand-binding proteins was investigated here. Cis -resveratrol exhibited higher affinity for bovine serum albumin than trans -isomer, but the isomerization to cis -isomer decreased the polyphenol affinity for α-lactalbumin and β-lactoglobulin. For each protein, trans - and cis -resveratrol shared the same optimal docking site but showed clear diversity in the second best site. Protein ternary complex could be formed when trans -/ cis -resveratrol were added in the sequence. Moreover, photostability of resveratrol and antioxidant activity of the polyphenol-protein mixtures were also discussed. The results gathered here should provide further insight into protein-polyphenol interactions and be useful for the development of protein-based carriers for the polyphenols.
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DOI
高影响因子
ACS Omega
·
2017
·
IF 0
Shenshen Ouyang,Tao Wang,Ye Yu,Bin Yang,Juming Yao,Sheng Wang
Controlling the membrane surface properties such as hydrophobicity and hydrophilicity is critical to achieving desirable performance. For a long time, the difference between the surface wettabilities of superhydrophilic poly(m-phenylene isophthalamide) (PMIA) electrospun nanofibrous membranes (ESMs) and the superhydrophobic parent material is believed to arise from the poling effect induced by the electrospinning process and wicking caused by the porous membrane structure. In this study, the short-term poling effect was eliminated using a reference, centrifugally spun nanofibrous membrane that has a similar fiber morphology and specific surface area to those of the ESM; consequently, we investigated the changes in the surface properties of the ESM in detail. Chemical analysis by angle-resolved X-ray photoelectron spectroscopy revealed that the N and O concentrations are greater at the surface of the ESM. In addition, analysis of the membranes by attenuated total reflectance Fourier-transform infrared spectroscopy and Raman spectra revealed that large amounts of cis conformations of the amide bonds appeared on the surface of ESM after the electrospinning process. The results indicate that the remarkable surface properties of PMIA ESMs mainly arise from the change in the conformation of the amide groups from the stable trans form to the cis form. This change was confirmed by the subsequent in situ growth of Pt nanoparticles and the excellent dye adsorption capacity of the membrane.
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DOI
PubMed
COMPOSITES PART B-ENGINEERING
·
2025
·
IF 14.2
Xiangren Bai,Xiang Zhang,Dongdong Zhao,Xudong Rong,Naiqin Zhao,Chunnian He
Strain localization at grain boundaries (GBs) is one of the key factors contributing to the trade-off between strength and ductility in engineering alloys. To address this issue, we developed a unique perpendicular interlocking structure connecting the matrix GBs by introducing trans -granular graphene nano-shells (SGSs) via a two-step targeted localized Cu–Al interdiffusion process. In the as-built structure, the original GBs served as the soft component, while the perpendicularly intersecting SGSs acted as the hard component. This configuration not only promotes sustainable dislocation accumulation in the vicinity of the GBs but also facilitates plastic strain delocalization through stress shielding effects from the SGSs. By effectively impeding the extension of shear bands and redirecting crack propagation towards the grain interiors, these hetero-structured GBs contribute to reducing the intrinsic brittleness of GBs. Consequently, the SGS/AlCu composite demonstrates a remarkable balance of tensile strength (∼574 MPa) and ductility (∼17 %). Our findings suggest that restructuring the geometry of GBs in metallic alloys presents a promising strategy for mitigating strain localization at GBs, offering potential for enhancing the properties of metallic alloys in various engineering applications.
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高影响因子
iScience
·
2023
·
IF 5.8
Qilin Yu,Haohao Mao,Bowen Yang,Yahui Zhu,Cheng Sun,Zhiqiang Zhao,Yang Li,Yaobin Zhang
Electrical stimulation has been used to strengthen microbial extracellular electron transfer (EET), however, the deep-seated reasons remain unclear. Here we reported that Bacillus subtilis , a typical gram-positive bacterium capable of extracellular respiration, obtained a higher EET capacity after the electrical domestication. After the electrical domestication, the current generated by the EET of B. subtilis was 23.4-fold that of the control group without pre-domestication. Multiple lines of evidence in bacterial cells of B. subtilis , their cell walls, and a model tripeptide indicated that the polarization of amide groups after the electrical stimulation forwarded the H-bonds recombination and radical generation of protein-like substances to develop extracellular electron transfer via the proton-coupled pattern. The improved electrochemical properties of protein-like substances benefited the trans -cell-wall electron transfer and strengthen extracellular respiration. This study was the first exploration to promote microbial extracellular respiration by improving the electrochemical properties of protein-like substances in cell envelopes.
研究领域:
微生物学
·
生物物理学
·
电化学
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DOI
高影响因子
BRAZILIAN JOURNAL OF MEDICAL AND BIOLOGICAL RESEARCH
·
2023
·
IF 2.3
Omidi-Shahsavandi M.,Yaghmaei P.,Ahmadian S.,Ebrahim-Habibi A.
Amyloid fibrils are characteristic of several disorders including Alzheimer's disease (AD), with no cure or preventive therapy. Diminishing amyloid deposits using aromatic compounds is an interesting approach toward AD treatment. The present study examined the anti-fibrillogenic effects of silibinin and trans-chalcone in vitro, in vivo, and in silico on insulin amyloids. In vitro incubation of insulin at 37°C for 24 h induced amyloid formation. Addition of trans-chalcone and silibinin to insulin led to reduced amounts of fibrils as shown by thioflavin S fluorescence and Congo red absorption spectroscopy, with a better effect observed for silibinin. In vivo bilateral injection of fibrils formed by incubation of insulin in the presence or absence of silibinin and trans-chalcone or insulin fibrils plus the compounds in rats' hippocampus was performed to obtain AD characteristics. Passive avoidance (PA) test showed that treatment with both compounds efficiently increased latency compared with the model group. Histological investigation of the hippocampus in the cornu ammonis (CA1) and dentate gyrus (DG) regions of the rat's brain stained with hematoxylin-eosin and thioflavin S showed an inhibitory effect on amyloid aggregation and markedly reduced amyloid plaques. In silico, a docking experiment on native and fibrillar forms of insulin provided an insight onto the possible binding site of the compounds. In conclusion, these small aromatic compounds are suggested to have a protective effect on AD.
研究领域:
神经科学
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药理学
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分子生物学
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DOI
PubMed
高影响因子
FOOD SCIENCE AND BIOTECHNOLOGY
·
2016
·Vol. 25
·期 2
·631-636
·
IF 0.699
Huang Xiaojun,Nie Shaoping,Yang Meiyan,Xie Jianhua,Li Chang,Xie Mingyong
Nine different edible oil types from 7 cities in China were analyzed. Trans fatty acid (TFA) contents in edible oils were determined, TFA distribution characteristics were analyzed, and a risk assessment was performed. Total TFA contents varied from 0.075±0.011 to 2.243±0.770 g/100 g of oil, with a mean content of 0.66 g/100 g of oil. TFA contents differed among different oil types and among different cities. Generally speaking, oil samples from northern areas of China contained more TFA, and lard usually had higher levels of TFA than other oils. An exposure assessment showed that the estimated daily intake of TFA from Chinese edible oils was low, and a risk assessment indicated that there was a low risk for TFA consumption in Chinese edible oils.
研究领域:
营养学
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食品安全
·
公共卫生
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DOI
PubMed
高影响因子
BIOLOGICAL & PHARMACEUTICAL BULLETIN
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2015
·Vol. 38
·期 10
·1658-1662
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IF 1.828
Lu-yang Lu,Yuan Liu,Zhi-feng Zhang,Xiao-jun Gou,Jun-hao Jiang,Ji-zhong Zhang,Qian Yao
Pomegranate seed oil (PSO) has diverse bioactivities. It was hyphothesized that if PSO were employed to construct a trans-resveratrol-loaded self-nanoemulsifying drug delivery system (RES SNEDDS-PSO), not only could PSO serve as an oil phase but also exert synergistic effects with resveratrol to yield better therapeutic outcomes. In this study, we prepared RES SNEDDS-PSO for the first time to validate that hypothesis. The anti-inflammatory and anticancer activities of RES SNEDDS-PSO were compared with another SNEDDS composed of oil phase isopropyl palmitate (RES SNEDDS-IP). The results showed that upon exposure to a 10-fold amount of water, RES SNEDDS-PSO was converted into nanoemulsions with a mean size of 44 nm. Nanoemulsions enhanced the water solubility of resveratrol by 20-fold, significantly improved resveratrol stability in intestinal fluid, and slowed the decomposition of resveratrol in water by 1-fold. An in vivo anti-infection test showed that the degree of inflammatory swelling in mice given RES SNEDDS-PSO was only 60 and 76% that of the group fed with RES SNEDDS-IP at doses of 10 and 20 mg/kg, respectively. An in vitro anticancer study showed that the inhibitory rate of RES SNEDDS-PSO against MCF-7 breast cancer cells was 2.03- and 1.24-fold that of RES SNEDDS-IP at a concentration of 12.5 and 25 µg/mL, respectively. This study demonstrated that the newly developed SNEDDS may be a prospective formulation in the functional food and clinical fields.
研究领域:
药剂学
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生物医学
·
食品科学
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DOI
PubMed
高影响因子
PARTICLE & PARTICLE SYSTEMS CHARACTERIZATION
·
2018
·Vol. 35
·期 4
·1700447
·
IF 4.384
Lin Dai,Weiyan Zhu,Rui Liu,Chuanling Si
Self-nanoemulsifying drug delivery system (SNEDDS) is recently studied for enhancing the bioavailability of hydrophobic drugs, such as resveratrol (RSV). However, the functional design of SNEDDS for the drug structural protection is not studied yet. Here, this paper presents an efficient approach by adding lignin (a kind of abundant biomass resource) to enhance the stability of trans -RSV and meantime improve its oral bioavailability. Higher stability of trans -RSV (just decreased 2% to cis -RSV after 1 h under direct sunlight) is observed after loaded by lignin-containing SNEDDS (RSV/SLS SNEDDS). Low toxicity, high transfer efficiency (apparent permeability coefficient >1 × 10 −7 cm s −1 ), and bioavailability (1.371%) of RSV/SLS SNEDDS is successfully demonstrated in Caco-2 cells and rat model, respectively. This study serves to illustrate a simple, versatile, environmental, and economic sustainability approach to the development of nanodelivery systems for light instability drugs.
研究领域:
药剂学
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药物传递
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生物医学工程
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天然产物化学
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DOI
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2017
·
IF 3.154
Xiuhai Gan,Deyu Hu,Yanjiao Wang,Lu Yu,Baoan Song
A series of novel trans-ferulic acid derivatives containing a chalcone moiety were designed and synthesized to induce plant resistance. Antiviral activities of the compounds were evaluated. Bioassay results demonstrated that compounds F3, F6, F17, and F27 showed remarkable curative, protective, and inactivating activities against tobacco mosaic virus (TMV). With a 50% effective concentration (EC50) value of 98.78 μg mL–1, compound F27 exhibited the best protective activity compared with trans-ferulic acid (328.6 μg mL–1), dufulin (385.6 μg mL–1), and ningnanmycin (241.3 μg mL–1). This protective ability was associated with potentiation of defense-related enzyme activity and activation of photosynthesis of tobacco at an early stage. This notion was confirmed by up-regulated expression of stress responses and photosynthesis regulating proteins. This work revealed that F27 can induce resistance and enhance plant tolerance to TMV infection. Hence, F27 can be considered as a novel activator for inducing plant resistance.
研究领域:
植物科学
·
植物化学
·
病毒学
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DOI
PubMed
高影响因子
MOLECULES
·
2021
·Vol. 26
·期 14
·4263
·
IF 4.412
Yin Zheng,Yanhong Shang,Mengyun Li,Yunzhou Li,Wuqing Ouyang
Trichophyton rubrumcauses ringworm worldwide. Citral (CIT), extracted fromPectisplants, is a monoterpene and naturally composed of geometric isomers neral (cis-citral) and geranial (trans-citral). CIT has promising antifungal activities and ergosterol biosynthesis inhibition effects against several pathogenic fungi. However, no study has focused on neral and geranial againstT. rubrum, which hinders the clinical application of CIT. This study aimed to compare antifungal activities of neral and geranial and preliminarily elucidate their ergosterol biosynthesis inhibition mechanism againstT. rubrum. Herein, the disc diffusion assays, cellular leakage measurement, flow cytometry, SEM/TEM observation, sterol quantification, and sterol pattern change analyses were employed. The results showed geranial exhibited larger inhibition zones (p< 0.01 or 0.05), higher cellular leakage rates (p< 0.01), increased conidia with damaged membranes (p< 0.01) within 24 h, more distinct shriveled mycelium in SEM, prominent cellular material leakage, membrane damage, and morphological changes in TEM. Furthermore, geranial possessed more promising ergosterol biosynthesis inhibition effects than neral, and both induced the synthesis of 7-Dehydrodesmosterol and Cholesta-5,7,22,24-tetraen-3β-ol, which represented marker sterols when ERG6 was affected. These results suggest geranial is more potent than neral againstT. rubrum, and both inhibit ergosterol biosynthesis by affecting ERG6.Keywords:neral;geranial;Trichophyton rubrum;ergosterol biosynthesis;ERG6;citral;antifungal activity;dermatophytes
研究领域:
微生物学
·
药理学
·
真菌学
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DOI
PubMed
高影响因子
Bioactive Materials
·
2021
·
IF 14.593
Tinglei Huang,Shuang Li,Jianchen Fang,Fuli Li,Shuiping Tu
Tumor vasculature constitutes a formidable hurdle for the efficient delivery of cancer nanomedicine into tumors. The leverage of passive pathway through inter-endothelial gaps in tumor blood vessels might account for limited extravasation of nanomedicine into tumor microenvironment (TME). Herein, Annexin A1 antibody-installed mesoporous organosilica nanoplatforms carrying immunotherapeutics of anti-PD-L1 antibody (aPD-L1) and Indoximod are developed to target at caveolar Annexin-A1 protein of luminal endothelial cells and to trigger the active trans -endothelial transcytosis of nanomedicine mediated by caveolae. Such strategy enables rapid nanomedicine extravasation across tumor endothelium and relatively extensive accumulation in tumor interstitium. aPD-L1 and Indoximod release from aPD/ [email protected] in a reduction-responsive manner and synergistically facilitate the intratumoral infiltration of cytotoxic T lymphocytes and reverse the immunosuppressive TME, thus demonstrating substantial anti-tumor efficacy in subcutaneous 4T1 breast tumors and remarkable anti-metastatic capacity to extend the survival of 4T1 tumor metastasis model. Moreover, aPD/ [email protected] nanomedicine also exhibits distinct superiority over the combination therapy of free drugs to potently attenuate the progression of urethane-induced orthotopic lung cancers. Collectively, aPD/ [email protected] nanoplatforms with boosted delivery efficiency via antibody-activated trans -endothelial pathway and enhanced immunotherapeutic efficacy provides perspectives for the development of cancer nanomedicines.
研究领域:
纳米医学
·
癌症免疫疗法
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药物递送系统
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肿瘤微环境
·
生物医学工程
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DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）