PLoS One
·
2013
·Vol. 8
·期 8
·e71071
·
IF 3.73
Bo-xin Zhao,Ya-bin Sun,Sheng-qi Wang,Lian Duan,Qi-lu Huo,Fei Ren,Guo-feng Li
The expression and function of P-glycoprotein (P-gp) is associated with the phenotype of multi-drug resistance (MDR), leading chemotherapy failure of patients suffered with cancer. Grape seed procyanidin(GSP) is a natural polyphenol supplement with anti-inflammatory effect. Present study assessed a new use of GSP on the MDR reversal activity and its possible molecular mechanisms in MDR1-overpressing paclitaxel resistant ovarian cancer cells. Our results showed GSP significantly enhanced the cytotoxicity of paclitaxel and adriamycin in paclitaxel resistant A2780/T cells but its parental A2780 cells. Furthermore, GSP strongly inhibited P-gp expression by blocking MDR1 gene transcription, as well as, increased the intracellular accumulation of the P-gp substrate rhodamine-123 in A2780/T cells. Nuclear factor-κB(NF-κB) activity, IκB degradation level and NF-κB/p65 nuclear translocation induced by lipopolysaccharide (LPS) and receptor activator for nuclear factor-κB ligand (RANKL) were markedly inhibited by pre-treatment with GSP. Meanwhile, GSP inhibited MAPK/ERK pathway by decreasing the phosphorylation of ERK1/2, resulting in reduced the Y-box binding protein 1 (YB-1) activation with blocking its nuclear translocation. Moreover, the up-regulation of P-gp expression, the activation of AKT/NF-κB and MAPK/ERK pathway induced by LPS was attenuated by GSP administration. Compared with PDTC and U1026, inhibitor of NF-κB and MAPK/ERK respectively, GSP showed the same tendency of down-regulating NF-κB and MAPK/ERK mediated YB-1 activities. Thus, GSP reverses P-gp associated MDR by inhibiting the function and expression of P-gp through down-regulation of NF-κB activity and MAPK/ERK pathway mediated YB-1 nuclear translocation, offering insight into the mechanism of reversing MDR by natural polyphenol supplement compounds. GSP could be a new potential MDR reversal agent used for combination therapy with chemotherapeutics in clinic.
研究领域:
肿瘤学
·
药理学
·
分子生物学
·
细胞生物学
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DOI
PubMed
高影响因子
3 Biotech
·
2026
·Vol. 16
·期 8
·328
·
IF 3.1
Zhu Hengzhou,Zhu Xiaodan,Huang Xiaona,Qian Yiyang,Li Jiahui,Zhang Jiaying,Niu Dong,Jin Chunhui
Gastric cancer (GC) is a prevalent malignancy worldwide with high morbidity and mortality. Its insidious onset and lack of sensitive early biomarkers impede routine screening, so most patients present advanced or metastatic disease at first diagnosis, leading to poor prognosis and scarce curative options. Surgery, chemotherapy and targeted therapy serve as standard GC treatments, however their efficacy is restricted by metastasis, adverse reactions and drug resistance, which drives the rapid development of immune checkpoint inhibitor (ICI)-based immunotherapy. Although monoclonal antibodies targeting programmed cell death protein 1/programmed cell death 1 ligand 1 (PD-1/PD-L1) resulted in significant survival benefits for GC patients, some patients exhibited an ineffective response. Our previous study has shown that Weitiao No. 3 (WD-3) enhanced the efficacy of anti-PD-1 immunotherapy by regulating intestinal flora in gastric cancer (GC) mice, in this study, huPBMC-NOG-dKO mice and MGC803 cells were used for in vivo and in vitro functional validation to explore the regulatory mechanism of WD-3 in GC immunotherapy. 16 S rRNA sequencing analysis of mouse fecal samples demonstrated that WD-3 significantly enriched the intestinal abundance of Lachnospiraceae and Ruminococcaceae in GC model mice. Targeted serum metabolomics further verified that WD-3 markedly elevated serum isobutyric acid level in GC mice. Combined with HE staining and tumor growth monitoring, both the intestinal flora mixture consisting of Lachnospiraceae and Ruminococcaceae and isobutyric acid prominently enhanced the anti-tumor efficacy of PD-L1 inhibitors in GC mice. Mechanistically, RNA sequencing and qRT-PCR assays identified ACOX2 as the most significantly up-regulated gene in isobutyric acid-treated MGC803 cells. Functional experiments using CCK-8 assay and flow cytometry revealed that isobutyric acid inhibited the viability and induced apoptosis of MGC803 cells, and such phenotypic changes were effectively rescued by ACOX2 knockdown. Furthermore, results from the CytoTox 96 cytotoxicity assay and ELISA revealed that combined treatment with isobutyric acid and PD-L1 inhibitor elevated the levels of LDH, IL-2, TNF-α, IFN-γ, Perforin 1 and GzmB, while suppressing IL-8, PD-1 and TIM-3 expression in CD8⁺ T cells co-cultured with MGC803 cells. Notably, all these regulatory effects were abrogated when MGC803 cells were transfected with si-ACOX2. These results suggested that WD-3 modulated intestinal flora to elevate isobutyric acid level, thereby enhancing the inhibitory effect of PD-L1 inhibitor on tumor growth and boosting the anti-tumor activity of CD8⁺ T cells by up-regulating ACOX2 expression in GC. These findings may provide novel targets for improving anti-PD-L1 therapy against GC.
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DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2026
·
IF 8.7
Qing Zhang,Chenguang Liu,Sirui Wu,Nan Zhong,Junfeng Qiu,Wei Fu,Xujun You
Purpose: Prostate cancer (PCa) remains a leading cause of cancer-related mortality in men, with current treatments often limited by drug resistance and systemic toxicity. Although traditional Chinese medicine components such as Astragaloside IV and polypeptide extract from scorpion venom (PESV) have demonstrated promising antitumor activity, their clinical translation is hampered by poor bioavailability and lack of tumor specificity. To address these limitations, we engineered an E3 aptamer-modified T cell-derived exosomal nanoplatform (EAPE) for the targeted co-delivery of Astragaloside IV and PESV in prostate cancer therapy.Methods: EAPE was constructed and characterized, and its targeting capability, biosafety, and therapeutic performance were evaluated in vitro and in vivo. In vitro, the antitumor efficacy was assessed by proliferation, migration and apoptosis assays, while the immunomodulatory effects were investigated using a co-culture system of LNCaP cells and T lymphocytes. In vivo, the antitumor efficacy and immune activation were examined in prostate cancer xenograft mouse model, with tumor growth inhibition, apoptosis and immune responses measured.Results: EAPE demonstrated efficient tumor-targeting capability and favorable biosafety profiles both in vitro and in vivo. EAPE demonstrated superior therapeutic efficacy against PCa by inhibiting proliferation and migration of prostate cancer cells and inducing apoptosis, while suppressing immunosuppression and activating antitumor immune response.Conclusion: This study presents a biologically derived, targeted nanodelivery system that improves the delivery efficiency and therapeutic efficacy of Astragaloside IV and PESV. These findings support the potential of exosome-based nanoplatforms as promising strategies for enhancing the translational application of traditional Chinese medicine-derived therapeutics in prostate cancer.
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DOI
PubMed
高影响因子
JOURNAL OF CHEMICAL THERMODYNAMICS
·
2022
·
IF 3.269
Zhan-Ping Qiao,Xin Chen,Qi-Chao Yang
Using an isothermal equilibrium method, the phase equilibrium of the ternary systems CsCl–CdCl 2 –H 2 O and CsBr–CdBr 2 –H 2 O were studied at T = 298.1 K. In the phase diagram of the system CsCl–CdCl 2 –H 2 O, the solid phases of CsCdCl 3 and Cs 2 CdCl 4 , besides CsCl and CdCl 2 ·2.5H 2 O, were discovered. The phase diagram of the system CsBr–CdBr 2 –H 2 O contains five crystallization fields for the solid phases CdBr 2 ·4H 2 O, CsCdBr 3 , Cs 5 Cd 2 Br 9 , Cs 3 CdBr 5 and CsBr. The new solid phases of CsCdCl 3 and CsCdBr 3 are congruently soluble, and Cs 2 CdCl 4 , Cs 5 Cd 2 Br 9 and Cs 3 CdBr 5 are incongruently soluble in the aqueous system. The experimental solubility data and phase diagram s for the ternary systems show more practical application for the obtained cadmium-based halide perovskite. The five new solid phase have been analyzed by X-ray diffraction and thermogravimetry/derivative thermogravimetry. By measuring the standard molar enthalpies of solution of the compounds, the standard molar enthalpies of formation of CsCdCl 3 , Cs 2 CdCl 4 , CsCdBr 3 , Cs 5 Cd 2 Br 9 , Cs 3 CdBr 5 were determined to be –(873.3 ± 0.7) kJ·mol −1 , –(1325.6 ± 0.9) kJ·mol −1 , –(742.8 ± 0.7) kJ·mol −1 , –(2710.0 ± 1.3) kJ·mol −1 and –(1558.1 ± 1.0) kJ·mol −1 , respectively.
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高影响因子
JOURNAL OF CHEMICAL AND ENGINEERING DATA
·
2021
·
IF 2.694
Kangling Yin,Li Chen,Feng Liu,Taotao Fan,Zongcheng Yan
Aiming at developing more biocompatible and economic separation platforms, aqueous biphasic systems (ABS) composed of deep eutectic solvents (DES) and tert-butanol were proposed for the first time. The effects of key factors such as the hydrogen-bond donor (HBD) properties and temperature on the phase-forming ability of DES/tert-butanol ABS were investigated. Meanwhile, syringic acid and eugenol mixtures were selected as model biomolecules to evaluate the efficiency of DES/tert-butanol ABS to use as liquid–liquid extraction systems. The results indicated that DES components migrated preferentially to the bottom phase while tert-butanol was concentrated in the top phase. The more hydrophilic HBD or lower temperature was responsible for greater efficiency to induce the formation of DES/tert-butanol ABS. The reason for phase separation was the incompatibility of the hydrogen-bond acceptor (HBA) and HBD with tert-butanol in aqueous solution, where the higher hydrophilic HBD enriched favorably in the lower phase, allowing for the formation of the DES/tert-butanol ABS. The selective separation of syringic acid and eugenol was a consequence of the HBD characters, temperature, and tie-lines length of the ABS, and they could be greatly separated by using the ABS composed of betaine-xylitol (DES) and tert-butanol at 298.15 K. The highest extraction efficiency of syringic acid and eugenol was 91.64 and 97.62%, respectively. Further, syringic acid and eugenol as well as DES can be recovered and reused by using water as the antisolvent and the vacuum distillation method. This study may be expected to lay a solid foundation for the expansion of DES-based ABS and selective separation of similar biomolecules.
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高影响因子
JOURNAL OF CHEMICAL AND ENGINEERING DATA
·
2019
·
IF 2.298
Wenjun Zhu,Yuwen Fan,Qiang Xu,Xinxin Liu,Bin Heng,Wenge Yang,Yonghong Hu
In this research, solubility of l-tryptophan in water, methanol, ethanol, acetone, isopropanol, n-butanol, acetonitrile, ethyl acetate, organic pure solvent, and in three binary mixed solvents (water + acetonitrile), (water + methanol), and (water + isopropanol) at the temperature range of T = 278.15–333.15 K was determined with the gravimetric method. The experimental results show that the solubility of l-tryptophan in the above solvents increased as temperature rose, and it achieved the highest dissolution efficiency in water. The improved Apelblat model, the Buchowski–Ksiazaczak λh model, the Redlich–Kister (CNIBS/R–K) model, and the Jouyban–Acree model were used to nonlinearly fit the experimental data of solubility, and the consistency was good. The physicochemical information of l-tryptophan provided in this report may be helpful for its extraction/separation, recrystallization, purification, and formulation development.
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高影响因子
ChemSusChem
·
2023
·Vol. 16
·期 10
·e202300067
·
IF 8.4
Wenhao Liu,Xuanpeng Wang,Jinshuai Liu,Changyuan Guo,Fan Qiao,Xiaoling Ding,Xiaobin Liao,Chunhua Han
To better satisfy the increasing demands for electric vehicles, it is crucial to develop fast-charging lithium-ion batteries (LIBs). However, the fast-charging capability of commercial graphite anodes is limited by the sluggish Li + insertion kinetics. Herein, we report a synergistic engineering of uniform nano-sized T-Nb 2 O 5 particles on graphite (Gr@Nb 2 O 5 ) with C−O−Nb heterointerfaces, which prevents the growth and aggregation of T-Nb 2 O 5 nanoparticles. Through detailed theoretical calculations and pair distribution function analysis, the stable existence of the heterointerfaces is proved, which can accelerate the electron/ion transport. These heterointerfaces endow Gr@Nb 2 O 5 anodes with high ionic conductivity and excellent structural stability. Consequently, Gr@10-Nb 2 O 5 anode, where the mass ratio of T-Nb 2 O 5 /graphite=10/100, exhibits excellent cyclic stability and incredible rate capabilities, with 100.5 mAh g −1 after 10000 stable cycles at an ultrahigh rate of 20 C. In addition, the synergistic Li + storage mechanism is revealed by systematic electrochemical characterizations and in situ X-ray diffraction. This work offers new insights to the reasonable design of fast-charging graphite-based anodes for the next generation of LIBs. Graphical Bond together : Benefiting from the C−O−Nb heterointerfaces that can effectively enhance the structure stability and facilitate electron/ion transport, composite of T-Nb 2 O 5 particles decorated on graphite exhibits low interfacial resistance, high Li + diffusion coefficient (nearly 34 times higher than graphite), and a high discharge capacity of 100.5 mAh g −1 after 10000 cycles at 20 C.
研究领域:
材料科学
·
电化学
·
能源存储
·
纳米材料
·
锂离子电池
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DOI
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2020
·
IF 3.943
Simiao Qiao,Xingpan Lian,Mengfan Yue,Qin Zhang,Zhifeng Wei,Li Chen,Yufeng Xia,Yue Dai
Previously, we reported that oral administration of madecassoside, the main active triterpene in Centella asiatica L., exerted anti-arthritis effect by inducing the generation of regulatory T (Treg) cells in small intestine. This study investigates the action site and mechanism of madecassoside to induce Treg cells. In collagen-induced arthritis (CIA) of rats, oral administration of madecassoside significantly alleviated arthritis symptoms, but its main metabolite madecassic acid did not, suggesting that madecassoside functions in the parent form. Madecassoside was shown to increase the number of Treg cells and promote the expression of Foxp3 and IL-10 in rat ileum rather than duodenum and jejunum, as detected using the immunohistochemistry assay and quantitative PCR assay, respectively. Unexpectedly, madecassoside was absent of significant effect on in vitro Treg cell differentiation and the expression of Foxp3 and IL-10. A combined use of broad-spectrum antibiotics resulted in significant reduction of the anti-arthritis effect of madecassoside in CIA rats. The 16S rRNA gene sequence showed that madecassoside could reverse the changes of gut microbiota under arthritis condition, and enrich several bacteria such as Lachnospiraceae, Butyricicoccus, Faecalibacterium, Butyricicoccus pullicaecorum and so on. GC-MS assay showed that madecassoside elevated the levels of acetic acid and butyric acid, but not other short chain fatty acids (SCFAs) in the cecum contents of CIA rats. Butyric acid rather than acetic acid could induce the in vitro differentiation of Treg cells and the expression of Foxp3 and IL-10. Accordingly, when madecassoside was co-administered with heptanoyl CoA, the competitive inhibitor of butyrate synthase, its effect on butyric acid production, Treg cell proportion and arthritis nearly disappeared. These findings indicate that oral madecassoside induces the generation of Treg cells and therefore displays anti-arthritis effect in the parent form but not metabolites, and the ileum is the main action site. The mechanism of madecassoside can be summarized as: expansion of the richness of butyrate-producing bacteria-up-regulation of intestinal butyrate level-induction of Treg cell differentiation and IL-10 expression.
研究领域:
免疫学
·
药理学
·
微生物学
·
风湿病学
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DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2021
·
IF 9.229
Wei Xiong,Lin Qi,Ning Jiang,Qi Zhao,Lingxiao Chen,Xin Jiang,Yuan Li,Zaigang Zhou,Jianliang Shen
Photodynamic therapy (PDT) is a promising strategy for cancer treatment. It can not only generate reactive oxygen species (ROS) to cause the chemical damage of tumor cells in the presence of enough oxygen but also promote the antitumor immunity of T cells through enhancing the production of interferon γ (IFN-γ). However, one phenomenon is ignored so far that the enhanced production of IFN-γ caused by PDT may significantly increase the expression of programmed death-ligand 1 (PD-L1) on the tumor cell membrane and thus could inhibit the immune killing effects of T cells. Herein, we report the construction of a composite by loading metformin (Met) and IR775 into a clinically usable liposome as a two-in-one nanoplatform (IR775@Met@Lip) to solve this problem. The IR775@Met@Lip could reverse tumor hypoxia to enhance ROS production to elicit more chemical damage. Besides, the overexpression of PD-L1 by PDT was also effectively down-regulated. These therapeutic benefits including decreased PD-L1 expression, alleviated T cell exhaustion, and reversed tumor hypoxia successfully suppressed both the primary and abscopal tumor growth in bladder and colon cancers, respectively. Combining with its excellent biocompatibility, our results indicate that this IR775@Met@Lip system has great potential to become a highly effective cancer therapy modality.
研究领域:
癌症研究
·
药学
·
免疫治疗
·
纳米技术
·
生物医学工程
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DOI
PubMed
高影响因子
JOURNAL OF CHEMICAL AND ENGINEERING DATA
·
2023
·
IF 2.6
Lingli Zhang,Renjie Xu
The mole fraction of 3-amino-6-bromopyridazine in methanol, ethanol, n-propanol, isopropanol, n-butanol, acetone, toluene, propylene glycol (PG), N,N-dimethylformamide (DMF), and water and methanol/ethanol//PG/DMF + water was experimentally measured by the isothermal saturation method from 278.15 to 323.15 K under 101.2 kPa. The solubility range of 3-amino-6-bromopyridazine is from 2.574 × 10–5 (water, 278.15 K) to 2.415 × 10–2 (DMF, 323.15 K). Accordingly, under the given conditions, the mixing of DMF and water is superior to other combinations in terms of dissolution. The solubility of 3-amino-6-bromopyridazine in mono-solvents was correlated with Apelblat, van’t Hoff, and λh models. Jouyban–Acree (J-A), modified Apelblat–Jouyban–Acree (A-J-A), and van’t Hoff–Jouyban–Acree (V-J-A) models were applied to calculate the solubility of 3-amino-6-bromopyridazine in four solvent mixtures. In terms of thermodynamic properties, the fusion enthalpy (ΔfusH = 37.01 kJ mol–1) and melting point (Tm = 472.15 K) of 3-amino-6-bromopyridazine are obtained by a differential scanning calorimeter. The interaction between the solute and solvent molecules as well as the interaction generated inside the above molecules could be analyzed through the calculation of the extended Hildebrand solubility parameter approach. The results showed that hydrophobic action of intramolecular groups and self-association of solute and solvent occurred in different concentration ranges.
研究领域:
化学工程
·
物理化学
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DOI
高影响因子
Applied Materials Today
·
2022
·
IF 8.663
Hua Zhang,Haijie Zhao,Yan Huang,Guodong Sun,Yi Zhang
The combination of chemotherapy and immunotherapy (also known as chemo/immunotherapy) promoted by nanomedicine has the potential to enhance the therapeutic effect in more patient populations. However, it is still affected by the inactivation of immune cells induced by traditional chemotherapy, which greatly impairs the synergistic effect of chemotherapy/immunotherapy substantially. Moreover, once tumor cells lose their MHC expression, the current popular CD8 + T cell-based immunotherapy may fail consequently. Herein, rapamycin, as mTOR signaling inhibitor associated with serious side effect once systemically administered, was incorporated into shell-core theranostic nanoplatform to augment synergy of chemotherapy and γδ T cell-mediated MHC-unrestricted immunotherapy against tumor without toxicity on γδ T cells. This nano-platform assembled from a cleavable shell and a carbonized polymer dot core can achieve accurate delivery of rapamycin with traceable imaging and cascade response. Such cascaded responsiveness has endowed it with improved blood compatibility, effective tumor accumulation, microenvironment-selective endocytosis, and hierarchical drug release facilitated by microenvironment-triggered programmable properties (size shrinkage, charge conversion and degradability) transition responding to blood-tissue-cells multi-level biological barriers. In vitro and in vivo experiments have shown that the nanoplatform not only promotes tumor chemotherapy by down-regulating mTOR signals, but also enhances γδ T cell-mediated immunotherapy by promoting the NKG2D pathway in a microenvironment-selective manner. In addition, the TCR-δ knockout mouse model was used to verify the synergy of chemical/immunotherapy promoted by the nanoplatform. In addition to multifunctional integrated therapeutic and diagnostic strategies, we also provide a paradigm to enhance the synergistic effect of chemotherapy/immunotherapy, and broaden the horizons of immunotherapy through γδ T cell-mediated replacement therapy assisted by nano-drugs.
研究领域:
纳米医学
·
癌症治疗
·
免疫学
·
药学
·
生物医学工程
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DOI
高影响因子
JOURNAL OF CHEMICAL AND ENGINEERING DATA
·
2021
·
IF 2.694
Zhi Wang,Liang Yao,Ting Wang,Zilong Cui,Jingling Ye,Yonghong Hu
In this study, the data on solid–liquid equilibrium of 4-[2-(N-methylcarbamyl)-4-pyridyloxy]aniline were studied by the gravimetric method. The solubility of 4-[2-(N-methylcarbamyl)-4-pyridyloxy]aniline was measured in 10 pure solvents (ethyl acetate, tetrahydrofuran, acetonitrile, dichloromethane, acetone, methanol, acetylacetone, n-propanol, n-butanol, and water) and three binary solvent mixtures (water + tetrahydrofuran, acetone + n-butanol, and ethyl acetate + n-propanol) in the temperature range of 278.15 to 323.15 K under atmospheric pressure. The experimental results show that the solubility of 4-[2-(N-methylcarbamyl)-4-pyridyloxy]aniline in the abovementioned solvents increases with the increase of temperature. Among the 10 pure solvents, ethyl acetate has the highest solubility. The improved Apelblat model, Buchowski–Ksiazaczak λh model, Redlich–Kister (CNIBS/R-K) model, and Jouyban–Acree model are used for nonlinear fitting of experimental data, and the KAT-LSER model is also used to study the relationship between the solubility of 4-[2-(N-methylcarbamyl)-4-pyridyloxy]aniline in pure solvents and the interaction between solvent and solute molecules. The physical and chemical information of 4-[2-(N-methylcarbamyl)-4-pyridyloxy]aniline provided in this report may help its extraction/separation, recrystallization, purification, and formulation development.
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高影响因子
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