FOOD CHEMISTRY
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2023
·
IF 8.8
Dan Yuan,Qi Li,Qibo Zhang,Feibai Zhou,Qiangzhong Zhao,Mouming Zhao
Nanocarrier-delivered bioactive compounds are highly desirable for their improved stability and applicability, but their bioavailability is still limited due to the strong mucus and epithelial cell barriers. Herein, a series of self-assembled soy protein nanoparticles (SPNPs) with different mucus permeabilities were prepared and their delivery efficiency upon Curcumin (Cur) encapsulation was evaluated. Results demonstrated that the formed SPNPs-Cur exhibited high compatibility and cellular antioxidant accessibility. Besides, SPNPs enhanced the cellular uptake and transmembrane permeation of Cur, especially promoted the transportation of proto-Cur in addition to Cur metabolites. The SPNPs with the rapid mucus diffusion capacity presented more efficient transcytosis across the Caco-2 cell monolayer, which was mediated by a combination of paracellular and transcellular pathways. This work verified that mucus-permeable soy protein nanoparticles could be a promising delivery system for improving the bioavailability of bioactive compounds.
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BIOMEDICINE & PHARMACOTHERAPY
·
2023
·
IF 7.5
Yiqian Zhang,Qianrui Huang,Qisi Xu,Chengsen Jia,Yong Xia
Triple negative breast cancer (TNBC) poses a significant clinical challenge due to its lack of targeted therapy options and the frequent development of chemotherapy resistance. Metastasis remains a primary cause of mortality in late-stage TNBC patients, underscoring the urgent need for alternative treatments. Repurposing existing drugs offers a promising strategy for the discovery of novel therapies. In this study, we investigated the potential of pimavanserin tartrate (PVT) as a treatment for TNBC. While previous studies have highlighted PVT's anticancer effects in various cancer types, its activity in TNBC remains unclear. Our investigation aimed to elucidate the anticancer effects and underlying mechanisms of PVT in TNBC. We evaluated the impact of PVT and combination treatments involving PVT on TNBC cell viability, apoptosis, autophagy, and associated signaling pathways. Our findings revealed that PVT may induce mitochondria-dependent intrinsic apoptosis and caused cytoprotective autophagy via the PI3K/Akt/mTOR pathway in TNBC cells in vitro . Notably, our study demonstrated strong synergistic anti-TNBC effects when combining PVT with doxorubicin. We also found PVT showed some efficacies to inhibit TNBC tumor growth in vivo . These results provided valuable insights into the potential of PVT as an anti-TNBC therapeutic and a possible option for enhancing the sensitivity of TNBC cells to conventional chemotherapy drugs. Further studies are needed to determine the activity and mechanism of PVT in inhibiting TNBC.
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2023
·
IF 6.1
Xiaolin Zhang,Zhen Dong,Yuanmiao Yang,Chaolong Liu,Jisheng Li,Wenli Sun,Yikang Zhu,Yang Shen,Zhi Wang,Muhan Lü,Hongjuan Cui
The incidence rate of colorectal cancer (CRC) has been increasing significantly in recent years, and it is urgent to develop novel drugs that have more effects for its treatment. It has been reported that many molecules extracted from the root bark of Morus alba L. (also known as Cortex Mori) have antitumor activities. In our study, we identified morusinol as a promising anticancer agent by selecting from 30 molecules extracted from Morus alba L. We found that morusinol treatment suppressed cell proliferation and promoted apoptosis of CRC cells in vitro. Besides this, we observed that morusinol induced cytoprotective autophagy. The GO analysis of differentially expressed genes from RNA-seq data showed that morusinol affected cholesterol metabolism. Then we found that key enzyme genes in the cholesterol biosynthesis pathway as well as the sterol regulatory element binding transcription factor 2 (SREBF2) were significantly downregulated. Furthermore, additional cholesterol treatment reversed the anti-CRC effect of morusinol. Interestingly, we also found that morusinol treatment could promote forkhead box O3 (FOXO3a) nuclear accumulation, which subsequently suppressed SREBF2 transcription. Then SREBF2-controlled cholesterol biosynthesis was blocked, resulting in the suppression of cell proliferation, promotion of apoptosis, and production of autophagy. The experiments in animal models also showed that morusinol significantly impeded tumor growth in mice models. Our results suggested that morusinol may be used as a candidate anticancer drug for the treatment of CRC.
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RESPIRATORY RESEARCH
·
2023
·Vol. 24
·期 1
·1-14
·
IF 5.8
Liu Jin,Chen Yuqian,Chen Huan,Wang Yan,Li Danyang,Zhang Qianqian,Chai Limin,Qiu Yuanjie,Zhang Jia,Shen Nirui,Wang Qingting,Wang Jian,Li Manxiang
Background Macrophage migration inhibitory factor (MIF) and GTPase dynamin-related protein 1 (Drp1)-dependent aberrant mitochondrial fission are closely linked to the pathogenesis of asthma. However, it is unclear whether Drp1-mediated mitochondrial fission and its downstream targets mediate MIF-induced proliferation of airway smooth muscle cells (ASMCs) in vitro and airway remodeling in chronic asthma models. The present study aims to clarify these issues. Methods In this study, primary cultured ASMCs and ovalbumin (OVA)-induced asthmatic rats were applied. Cell proliferation was detected by CCK-8 and EdU assays. Western blotting was used to detect extracellular signal-regulated kinase (ERK) 1/2, Drp1, autophagy-related markers and E-cadherin protein phosphorylation and expression. Inflammatory cytokines production, airway reactivity test, histological staining and immunohistochemical staining were conducted to evaluate the development of asthma. Transmission electron microscopy was used to observe the mitochondrial ultrastructure. Results In primary cultured ASMCs, MIF increased the phosphorylation level of Drp1 at the Ser616 site through activation of the ERK1/2 signaling pathway, which further activated autophagy and reduced E-cadherin expression, ultimately leading to ASMCs proliferation. In OVA-induced asthmatic rats, MIF inhibitor 4-iodo-6-phenylpyrimidine (4-IPP) treatment, suppression of mitochondrial fission by Mdivi-1 or inhibiting autophagy with chloroquine phosphate (CQ) all attenuated the development of airway remodeling. Conclusions The present study provides novel insights that MIF promotes airway remodeling in asthma by activating autophagy and degradation of E-cadherin via ERK/Drp1 signaling pathway, suggesting that targeting MIF/ERK/Drp1 might have potential therapeutic value for the prevention and treatment of asthma.
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SENSORS AND ACTUATORS B-CHEMICAL
·
2023
·
IF 8.4
Daxiu Li,Feng Qiu,Ruo Yuan,Yun Xiang
Simultaneous detection and quantification of antimalarial drugs is important for evaluating the spread of their resistance. On the base of the target-induced assembly of branched DNA nanostructure signal amplification and different electrochemical coding tags at distinct potentials, an aptasensing method for multiplexed and highly sensitive detection of piperaquine (PQ) and mefloquine (MQ) antimalarial drugs is established. The target drugs associate with and switch the conformation of the aptamers to release free ssDNA trigger sequences, which initiate the self-assembly of many methylene blue (MB)- and ferrocene (Fc)-labeled auxiliary signal sequences to form branched nano-assemblies on electrode. The electrode-captured MB and Fc tags thus yield highly magnified current reponses at well-resolved potentials for simultaneously monitoring PQ and MQ with respective detection limits as low as 0.061 ng mL −1 (i.e., 0.114 nM) and 0.17 ng mL −1 (i.e., 0.449 nM). Moreover, the simultaneous detection of PQ and MQ in diluted human serum samples has also been verified by the developed sensor, revealing its potential for multiplexed monitoring of different drugs in connection with the corresponding aptamers for various application purposes.
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PHARMAZIE
·
2021
·Vol. 76
·期 5
·195-201
·
IF 1.267
Dai Tianming,Wang Min,Wang Pengzhen,Dai Libing,Dai Renke,Meng Qingqi
The effects of eight oral anti-coronavirus drugs (lopinavir, ritonavir, chloroquine, darunavir, ribavirin, arbidol, favipiravir, oseltamivir) on the metabolism of four specific glycosides (polydatin, geniposide, quercitrin, glycyrrhizin) and on the activities of three major glycosidases
(β-glucosidase, α-rhamnosidase, β-glucuronidase) from gut microflora were explored in vitro and determined by LC-MS/MS. The metabolism of polydatin, geniposide, quercitrin and glycyrrhizin was significantly inhibited by one or several anti-coronavirus drugs of 100 μM
around 1 h and 4 h (P<0.05), among which darunavir could strongly reduce the production of genipin (70.6% reduction), quercitin (80.6% reduction) and glycyrrhetinic acid (37.9% reduction), which may cause a high risk of herb-drug interactions (HDI). Additionally, chloroquine reduced the
production of genipin and quercitin by more than 75% (P<0.05), whereas arbidol had no significant influence on the metabolism of polydatin, quercitrin and glycyrrhizin (P>0.05) so that its risk may be lower. The inhibition of darunavir on β-glucosidase was relatively strong (IC50
= 193±23 μM), and the inhibition became weaker on β-glucuronidase and α-rhamnosidase (IC50>500 μM). The consistency between gut microflora and glycosidase system indicated that the inhibition of darunavir on the activity of β-glucosidase and β-glucuronidase
may be the main reason for affecting the metabolism of geniposide, glycyrrhizin and polydatin in gut microflora. However, for the inhibition of darunavir and chloroquine on the metabolism of quercetrin, there was no correlation between gut microflora and α-rhamnosidase system. Assessing
the risk of HDI mediated by glycosidases in gut microflora may be conducive to the safety and efficacy of combining traditional herbal and Western medicine for the treatment of patients with Covid-19.
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MICROVASCULAR RESEARCH
·
2021
·
IF 3.514
Yi Wang,Yang Yao,Rong Li,Binghui Wu,Huiqin Lu,Jing Cheng,Zhe Liu,Junhui Du
Introduction Choroidal neovascularization (CNV) is the main pathological change of wet age-related macular degeneration. Anti-VEGF drugs are the most commonly used treatment for CNV. The biggest drawback of anti-VEGF drugs is the recurrence of CNV, which requires repeated therapy several times. Autophagy activation may be involved in reducing the therapeutic effect of anti-VEGF drugs. So, this study aims to elucidate the effect and mechanism of anti-VEGF drugs on endothelial autophagy and neovascularization in vitro. Methods RF/6A cells were randomly divided into five groups: The control group, hypoxia group (1% O 2 , 5% CO 2 , 94% N 2 ), anti-VEGF group (group1: Ranibizumab 100 μg/ml; group2: Aflibercept , 400 μg/ml; group3: Conbercept , 100 μg/ml). Autophagy-related proteins were examined by Western blot . RFP-GFP-LC3 was used to detect autophagy and autophagic flow. Subsequently, we used autophagy inhibitors (3-MA or CQ) to inhibit Conbercept induced autophagy and to observe its effect on angiogenesis in vitro. Proliferation, migration, and tube formation of endothelial cells can be used to study neovascularization in vitro. In this research, the CCK-8 assay was used to detect cell proliferation . Cell migration and tube formation were assessed by wound assay and matrix method, respectively. Flow cytometry and Tunel were used to detect cell apoptosis . Finally, the mechanism of Conbercept activated autophagy was studied. Western blot was used to detect the expression of p53 and DRAM (damage-regulated autophagy modulator), upstream activators of autophagy. Results The protein levels of Beclin-1 and LC3-2/1 in Ranibizumab and Conbercept groups were significantly higher than in the hypoxia group( P < 0.05). While the expression of P62 was decreased ( P < 0.05). The autophagic flux was showed the same results. However, Aflibercept showed the opposite effect on autophagy. Compared with the Conbercept group, autophagy inhibitor 3-MA or CQ can further inhibit cell proliferation and promotes cell apoptosis ( P < 0.05). Conbercept significantly inhibited cell migration compared with the hypoxia group (633.08 ± 72.52 vs. 546.33 ± 24.61), while the autophagy inhibitor group (3-MA or CQ) had a more obvious inhibition effect (309.75 ± 86.36 and 263.33 ± 68.67) ( P < 0.05). For tube formation, the number of tube formation was decreased significantly in the Conbercept group (32.00 ± 2.00) compared to the hypoxia group (39.00 ± 1.53) and even further reduced in 3-MA or CQ group (24.00 ± 3.61, 20.00 ± 2.65). The length of master segments in the hypoxia group was 15,668.00 ± 894.11. It was decreased in Conbercept (13,885.34 ± 730.03). In 3-MA or CQ group, the length of master segments dropped further (11,997.00 ± 433.66, 10,617.67 ± 543.21). Compare with the hypoxia group, the expression P53 and DRAM were increased in the Conbercept group ( P < 0.05). Autophagy-related proteins LC-3, Beclin-1, and DRAM were inhibited by P53 inhibitor Pifithrin-α (PFTα) ( P < 0.05). Conclusion Ranibizumab and Conbercept can trigger the autophagy of vascular endothelial cells while Aflibercept can inhibit it. The combination of Conbercept and autophagy inhibitor can significantly inhibit the formation of angiogenesis in vitro. The mechanism of autophagy activation is related to the activation of the p53/DRAM pathway.
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CARBOHYDRATE POLYMERS
·
2021
·
IF 9.381
Yu Zhang,Yan Liu,Yinxing Zhou,Ziming Zheng,Wenqi Tang,Mengzi Song,Jinglin Wang,Kaiping Wang
Lentinan (SLNT) has been shown to be directly cytotoxic to cancer cells. However, this direct antitumour effect has not been thoroughly investigated in vivo, and the mechanism remains unclear. We aimed to examine the direct antitumour effect of SLNT on human colon cancer and the mechanism in vivo and in vitro . SLNT significantly inhibited tumour growth and induced autophagy and endoplasmic reticulum stress (ERS) in HT-29 cells and tumour-bearing nonobese diabetic (NOD)/severe combined immunodeficiency (SCID) mice. Experiments with the autophagy inhibitors chloroquine (CQ) and 3-methyladenine (3-MA) showed that autophagy facilitated the antitumour effect of SLNT. Moreover, ERS was identified as the common upstream regulator of SLNT-induced increases in Ca 2+ concentrations, autophagy and apoptosis by using ERS inhibitors. In summary, our study demonstrated that SLNT exerted direct antitumour effects on human colon cancer via ERS-mediated autophagy and apoptosis, providing a novel understanding of SLNT as an anti-colon cancer therapy.
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LIFE SCIENCES
·
2021
·
IF 5.037
Dawei Yang,Xiaoyu Tian,Yuchen Ye,Yin Liang,Jie Zhao,Tao Wu,Na Lu
Senescent cancer cells contribute to tumor refractoriness. The removal of senescent cells after chemotherapy prevents or delays cancer relapse. Our study showed that GL-V9 (5-hydroxy-8-methoxy-2-phenyl-7-(4-(pyrrolidin-1-yl) butoxy)-4-H-chromen-4-one), a potential anticancer drug, eliminated senescent MEFs (Mouse embryonic fibroblasts) and drug-induced senescent breast cancer cells. GL-V9 induced apoptosis in senescent MDA-MB-231 cells. Mechanistically, it alkalized lysosomes and increased the abundance of mitochondria as well as ROS (Reactive oxygen species). The senolytic effect of GL-V9 was also observed in epirubicin-treated mammary tumors in MMTV-PyMT mice. Our data thus indicated that GL-V9 is a promising senolytic drug which could be used to improve the outcome of cancer chemotherapy.
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EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
·
2021
·
IF 4.384
Tianming Dai,Weifan Jiang,Min Wang,Zizheng Guo,Renke Dai
Generally, two-period cross-over design is used in bioequivalence (BE) study. High intra-subject variability of gefitinib was reported in a clinical BE study, and significant changes in gefitinib exposures were observed among different periods in our previous BE study in dogs. Therefore, commercial gefitinib tablets from the same batch were used in the present study and assigned to two groups: the testing drug (GF1) group and the reference drug (GF2) group. A single-oral-dose, two-period cross-over study with a 7-day washout (approximately 24 half-lives) under fasting condition was conducted in 12 dogs to explore the factors. The results showed that the mean values of AUC (0–t) , AUC (0-∞) , C max and T max of these two GF1 and GF2 groups were similar. However, the GF1 and GF2 did not meet the acceptance criteria of bioequivalence with 90% confidence intervals, since the values obtained were 76.22%-117.43% for AUC (0-t) and 87.55%-131.59% for C max . ANOVA revealed a significant difference between the two periods ( P < 0.05). Interestingly, the mean AUC (0-t) of gefitinib in the period 2 was 2.3-fold greater than that in the period 1, while C max in the period 2 was 1.7-fold higher than that in the period 1. However, the volume of distribution was significantly decreased, becoming 0.4-fold lower in the period 2. No statistically significant difference in the half-life and T max was observed between the two periods ( P < 0.05). The pharmacokinetic alteration might come from the different physiological absorption and/or metabolism between periods. Since a 7-day washout interval was applied, DDI risk from P450s and/or P-gp would not play a significant role in the non-bioequivalence. As regard the variability, the intra-subject variation crossing the periods was much larger than the inter-subject variation within each period. The absorption and/or metabolism function of the gut bacteria might play an important role in the increasing exposure of gefitinib in the second period, especially with the comparison with the analysis from the high-fat-diet treatments in humans. Therefore, further studies might be needed to evaluate whether the assessment of bioequivalence could be facilitated by a much longer washout interval allowing the recovery of gut bacteria.
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PLoS Genetics
·
2021
·Vol. 17
·期 7
·e1009527
·
IF 5.917
Jun Yang,Hao Guo,Nan-Ji Jiang,Rui Tang,Guo-Cheng Li,Ling-Qiao Huang,Joop J. A. van Loon,Chen-Zhu Wang
Glucosinolates are token stimuli in host selection of many crucifer specialist insects, but the underlying molecular basis for host selection in these insects remains enigmatic. Using a combination of behavioral, electrophysiological, and molecular methods, we investigate glucosinolate receptors in the cabbage butterfly Pieris rapae . Sinigrin, as a potent feeding stimulant, elicited activity in larval maxillary lateral sensilla styloconica, as well as in adult medial tarsal sensilla. Two P . rapae gustatory receptor genes PrapGr28 and PrapGr15 were identified with high expression in female tarsi, and the subsequent functional analyses showed that Xenopus oocytes only expressing PrapGr28 had specific responses to sinigrin; when ectopically expressed in Drosophila sugar sensing neurons, PrapGr28 conferred sinigrin sensitivity to these neurons. RNA interference experiments further showed that knockdown of PrapGr28 reduced the sensitivity of adult medial tarsal sensilla to sinigrin. Taken together, we conclude that PrapGr28 is a gustatory receptor tuned to sinigrin in P . rapae , which paves the way for revealing the molecular basis of the relationships between crucifer plants and their specialist insects.
Preference of crucifer specialist insects to glucosinolates is well known in the field of insect-plant interactions, but its molecular basis is unclear. This study uses an integrative approach to investigate the molecular basis of glucosinolate detection by gustatory receptor neurons in the larval mouthparts and adult forelegs of the cabbage butterfly Pieris rapae , and finally reveal that PrapGr28 is a bitter receptor tuned to sinigrin. The current work takes a significant step towards identifying gustatory receptors tuned to glucosinolates, crucial recognition signals in crucifer host plants, providing insights into co-evolution of herbivorous insects and their host plants.
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MICROCHIMICA ACTA
·
2020
·Vol. 187
·期 8
·1-9
·
IF 6.232
Xu Shaomei,He Xu,Huang Yibing,Liu Xin,Zhao Lihe,Wang Xinghua,Sun Ying,Ma Pinyi,Song Daqian
A hydrothermal method has been employed to synthesize a green and one-pot carbon dots-based sensor for ratiometric monitoring and imaging lysosomal pH in living cells. The carbon dots were directly functionalized by abundant amino groups during synthesis and exhibited dual emission bands at 439 and 550 nm under single-wavelength excitation of 380 nm without any additional modification. In addition to its small size, the established sensor had good biocompatibility. Owing to its abundant amino groups and good hydrophilicity, the sensor is able to target lysosome with high Pearson’s colocalization coefficients (0.935 and 0.924) and responds to change of lysosomal pH in living cells. It also had excellent pH sensitivity and reversibility, and anti-interference capability, thus enabling sensing pH change in intracellular environment in real time, as demonstrated by successful monitoring of lysosomal pH changes during lysosomal alkalization, dexamethasone-induced stimulation, and stress in Michigan Cancer Foundation-7 cells (blue channel, excitation = 405 nm and emission = 419–459 nm bandpass; and yellow channel, excitation = 405 nm and emission = 530–570 nm bandpass).
Graphical abstract
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危险品化学品经营许可证（带存储）