JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2023
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IF 6.1
Siyu Wang,Lutong Wang,Jingwen Xu,Yihai Wang,Limin Xiang,Xiangjiu He
The berries of black nightshade (Solanum nigrum L.) are consumed as a favorite fruit in some regions and have been reported to possess a range of biological activities. Previous studies have found that the steroidal saponins from the berries of S. nigrum (SN) showed potential antileukemic activity, although the underlying mechanism remains to be revealed. This study investigated the effects and mechanisms of SN in combination with adriamycin to reverse leukemia multidrug resistance in vivo and in vitro. The results indicated that the combination of SN and adriamycin displayed enhanced suppression ability both in vitro and in vivo by the modulation of drug efflux proteins. Further study revealed that SN and adriamycin co-treatment induced cell apoptosis in K562/ADR cells through caspase pathways and autophagy through the PI3K/Akt/mTOR and MAPK signaling pathway. This study provides a new prospect of the berries of black nightshade in multidrug resistance therapy of cancer.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2022
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IF 8.025
Dan Shao,Qiang Gao,Yanshan Sheng,Shangji Li,Yong Kong
An intelligent drug delivery platform based on the hybrids of mesoporous silica nanoparticles (MSN), sodium hyaluronate (HA), chitosan (CS) and oxidized sodium carboxymethyl cellulose (oxCMC) is developed, which can be used for dual-responsive dual-drug delivery. Hydrophilic cytarabine (Cyt) is first loaded into the mesopores of the aminated MSN (NH 2 -MSN), which is encapsulated by the hydrogel of HA and cystamine (Cys) crosslinked via amidation . The Cyt encapsulated hydrogel which is denoted as Cyt/NH 2 -MSN/HA is co-encapsulated with hydrophobic methotrexate (MTX) into the hydrogel of CS and oxCMC resulted from Schiff base reaction. Since the acylhydrazone bonds (–HC=N–) between CS and oxCMC are sensitive to pH and the disulfide bonds (–S–S–) in Cys are sensitive to glutathione (GSH), the resultant dual-drug encapsulated hydrogel, denoted as Cyt/NH 2 -MSN/HA/MTX/CS/oxCMC, can be used for dual-responsive (pH and GSH) drug delivery. The results of cell viability demonstrate that the developed dual-drug encapsulated hydrogel has significantly higher efficacy of chemotherapy than that of single-drug (MTX or Cyt) encapsulated hydrogel.
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NEUROSCIENCE
·
2022
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IF 3.708
Jie Zhao,Yue Wu,Shanshan Liang,Xiangyu Piao
Ferroptosis, an iron-dependent form of non-apoptotic cell death, is reportedly responsible for cerebral ischemia/reperfusion (I/R) injury. Evidence has shown that spermidine/spermine N1-acetyltransferase 1 (SSAT1) activation-induced ferroptosis is associated with upregulation of arachidonate 15-Lipoxygenase (ALOX15). Our previous study has revealed that upregulation of ALOX15 contributes to cerebral I/R injury via inducing microglial activation. The current study aimed to investigate the role of SSAT1/ALOX15 axis in neuronal ferroptosis after I/R. We found that the expression of SSAT1 was upregulated in the cortical penumbra of mice subjected to transient middle cerebral artery occlusion and reperfusion (tMCAO/R). Knockdown of SSAT1 mitigated I/R-induced cerebral infarction and neurological impairments, as well as decreased cortical iron contents, reactive oxygen species (ROS) generation and 4-Hydroxynonenal (4-HNE) level. Further in vitro evidence revealed that knockdown of SSAT1 downregulated the expression of ALOX15 in the primary cortical neurons exposed to tertbutyl-hydroksyperoxide (TBH). In addition, loss of neuronal viability and production of lipid hydroperoxides were inhibited in TBH-treated neurons when SSAT1 was knocked down. Mechanistically, SSAT1 overexpression decreased the expression levels of two key ferroptotic repressors, glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11) in TBH-stimulated neurons. Treatment with the ALOX15 inhibitor PD146176 or ferroptosis inhibitor ferrostatin-1 partially reversed SSAT1 upregulation-induced ferroptosis and viability loss in TBH-treated neurons. These results together indicate that the activation of SSAT1/ALOX15 axis may aggravate cerebral I/R injury via triggering neuronal ferroptosis, providing novel insights into cerebral injury associated with lipid peroxidation.
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Journal of Saudi Chemical Society
·
2021
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IF 3.932
Lefeng Liu,Zhiguo Xu,Yang Liu,Zheng-Zhi Yin,Yanshan Sheng,Chengqiang Ding,Yong Kong
Cytarabine (Cyt) encapsulated calcium carbonate (CaCO 3 ) nanospheres were facilely synthesized through a simple co-precipitation method, and the Cyt encapsulated CaCO 3 nanospheres (CaCO 3 /Cyt) were modified by polyacrylic acid (PAA) hydrogels through in situ polymerization of acrylic acid (AA) monomer on the surface of the CaCO 3 /Cyt. Successful preparation of the Cyt loaded CaCO 3 /PAA hydrogels were confirmed by the characterization of SEM, TEM and FT-IR. Premature release of Cyt in acidic medium (pH = 1.2) could be effectively circumvented by the introduction of the PAA hydrogels. More importantly, pH-responsive delivery of Cyt from the as-prepared CaCO 3 /PAA hydrogels could be achieved due to the pH-sensitivity of the PAA. Although the highest swelling ratio of PAA was obtained at pH 7.3 (27.7), the highest cumulative release of Cyt from the carrier was achieved at pH 5.3 (86.75%), which might be attributed to the high stability of CaCO 3 at pH 7.3. That is to say, the highest cumulative release of Cyt at pH 5.3 was a compromise by considering the relatively high swelling ratio of PAA and the relatively low stability of CaCO 3 .
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Journal of Materials Research and Technology-JMR&T
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2021
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IF 5.039
Yuzhe Chen,Wenxuan Zhao,Honglian Dai
Chitosan (CS) is a type of natural polysaccharide, widely used as a biomaterial on account of its great biocompatibility and the multitudes of functional groups on the long chitosan chain, making it easy for property augmentations. Nevertheless, the lack of workability and mechanical capacity limits the applications. Herein, electrospinning was chosen to fabricate oriented chitosan/polyethylene oxide (PEO) nanofibres decorated by integrin-targeting polypeptides (RGD, Arg-Gly-Asp), which is essential for cell adhesion. At the same time, porous PLGA-PEG membranes were taken as a shell of the composite film, which can provide mechanical support for the scaffold. Adequate topological anisotropic information from oriented nanofibres helps the scaffold simulate the natural axon structure, which can induce accelerated regeneration of neurotmesis. Moreover, β-Tricalcium Phosphate (β-TCP) nanoparticles were brought into nanofibers to neutralize the acidic environment produced by the degeneration of PLGA-PEG. Cell viability tests at the in vitro level and dorsal root ganglion (DRG, 1-day sucking SD rat) co-culture detection proved that the scaffold possesses excellent biocompatibility while guiding oriented regeneration of damaged nerves. In this study, a CS-RGD/PEO/β-TCP/PLGA-PEG porous composite scaffold with low cytotoxicity was fabricated. The scaffold can not only lead to the oriented growth of nerves but also has selectivity, which can help nutrient exchange while inhibiting the invasion of fibrous tissue.
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JOURNAL OF COLLOID AND INTERFACE SCIENCE
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2021
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IF 8.128
Kai Chen,Yong Qian,Chaoyang Wang,Dongjie Yang,Xueqing Qiu,Bernard P. Binks
Hypothesis The stability of anti-cancer drugs and the adverse drug reactions (ADRs) caused by drug-drug interactions (DDIs) are two major challenges of combination chemotherapy. In this work, hydrophilic drug loaded lignin-based nanoparticles were applied to stabilize high internal phase Pickering emulsions (HIPPEs) containing hydrophobic drug in the oil phase, which not only improved the stability of anti-cancer drugs, but also reduced the risk of DDIs. Experiments Highly biocompatible enzymatic hydrolysis lignin/chitosan oligosaccharide (EHL/COS-x) nanoparticles were prepared and used to load hydrophilic cytarabine (Ara-C). The morphology, loading capacity, encapsulation efficiency and emulsifying properties of nanoparticles were characterized and predicted. Subsequently, these nanoparticles were applied to stabilize HIPPEs with soybean oil containing hydrophobic curcumin as dispersed phase. The effects of the morphology, amphipathy and concentration of nanoparticles and oil/water ratio on the microstructure and stability of HIPPEs were investigated. Meanwhile, the controlled release, protective performance, cytotoxicity and bio-activity of HIPPEs were also evaluated. Findings EHL/COS-x nanoparticles loaded with Ara-C could stabilize HIPEs with 85 vol% soybean oil containing curcumin. The two drugs were separately loaded in same delivery system, which effectively lowered the risk of DDIs. Meanwhile, HIPPEs provided outstanding UV, thermal and oxidation protection for these two environmentally sensitive anti-cancer drugs. In addition, HIPPEs displayed a good pH-responsive release in a tumor environment. In vitro experiments show that the killing efficiency of two drugs co-loaded HIPPEs against the leukemia cell is two times higher than that of single drug loaded systems. This strategy can be extended to the synergistic therapy of two or more drugs with different physicochemical properties.
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INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2020
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IF 4.845
Qiang Gao,Jun Gao,Chengqiang Ding,Shangji Li,Linhong Deng,Yong Kong
Au nanoclusters, decorated with graphene quantum dots (GQDs), were obtained through photocatalytic reduction of AuCl 4 3– by UV irradiation, and then cytarabine (Cyt) was loaded to the Au/GQDs via charge-dipole interactions. Mercaptopropionic acid (MPA) was anchored to the Cyt-loaded Au/GQDs through the formation of Au–S bond, which was further encapsulated by polyethyleneimine (PEI) via charge-dipole interactions. The delivery of Cyt from the quaternary complex (Au/GQDs/MPA/PEI) is pH-sensitive and can be modulated by near-infrared (NIR) irradiation. The results of cell viability test indicate that the developed nanoplatform can be used for chemo-photothermal combination therapy of cancer cells, and the efficacy of chemo-photothermal combination therapy is significantly higher than that of the single mode of photothermal therapy (PTT) or chemotherapy.
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Materials Science & Engineering C-Materials for Biological Applications
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2020
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IF 5.88
Yanshan Sheng,Wei Dai,Jun Gao,Hongda Li,Wensheng Tan,Jingwei Wang,Linhong Deng,Yong Kong
Graphene quantum dots (GQDs) were prepared by the pyrolysis of citric acid (CA), which were used for the loading of hydrophilic cytarabine (Cyt), an anti-cancer drug, and then wrapped with chitosan (CS) gels for the encapsulation of the loaded Cyt. The fluorescent stability of GQDs was significantly enhanced in the presence of CS, which might be attributed to the inhibited agglomeration of GQDs by the CS gels. In addition, the burst release of Cyt from the developed carrier was also effectively relieved by the CS coating. Since the incorporation of Cyt into GQDs was achieved by amidation reaction, the delivery of Cyt from the carrier was pH-sensitive due to the hydrolysis of the amido linkage between GQDs and Cyt in acidic medium.
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Nanoscale
·
2019
·Vol. 11
·期 47
·23000-23012
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IF 6.97
Zhigang Fang,Xiaozhen Wang,Yanling Sun,Ruifang Fan,Zhong Liu,Rui Guo,Deming Xie
Cytarabine (Ara-C) is an essential medicine used in the clinical treatment of acute lymphoblastic leukemia. However, Ara-C suffers from high hydrophilicity, rapid plasma degradation and significant side effects. Thus, herein, to eliminate the limitations of Ara-C in the treatment of leukemia, Sgc8 aptamer targeting and glutathione (GSH)-responsive polymeric micelles (PCL-ss-Ara@Sgc8-BSA) were prepared. The prodrug was synthesized via covalent bond formation between acryloyl chloride-terminal PCL-ss-PCL and Ara-C, and surface decoration with Sgc8-bovine serum albumin (Sgc8-BSA). The obtained PCL-ss-Ara@Sgc8-BSA exhibited good GSH-responsive drug release behavior, obvious targetability and sufficient antitumor effect to acute lymphoblastic leukemia (ALL) cells (CCRF-CEM). A hemolysis test was further carried out to demonstrate that these polymeric micelles are safe to be administrated intravenously. Compared with free Ara-C, PCL-ss-Ara@Sgc8-BSA significantly enhanced tumor growth inhibition in mice bearing CCRF-CEM xenograft tumors, while causing little side effects, and improved the survival rate of CCRF-CEM tumor-bearing mice in vivo. Therefore, this new self-assembling small molecular prodrug equipped with Sgc8 targeting function is a potential treatment for the targeted therapy of acute lymphoblastic leukemia.
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BIOCHEMICAL GENETICS
·
2022
·Vol. 61
·期 3
·916-930
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IF 2.22
Wang Pengwei,Mao Senlin,Yi Tingting,Wang Lihua
Vascular dementia (VaD) is the second most common subtype of dementia, but the precise mechanism underlying VaD is not fully understood. Long non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) can act as a key regulator in physiological and pathological processes, including neurological disorders, but whether it is correlated with VaD has not been elucidated. In this study, we established a mouse model of VaD by the transient bilateral common carotid artery occlusion surgery. As expected, the Morris water maze showed that VaD mice had significant deficits in spatial learning and memory. MALAT1 was elevated in the hippocampus of VaD mice. Additionally, we found that microRNA (miR)-9-3p was downregulated in the VaD hippocampus. By performing a dual-luciferase report assay, we verified the binding relationship between MALAT1 and miR-9-3p. Interestingly, synapse-associated protein-97 (SAP97), a well-known gene related to synaptic functions, was found upregulated in the hippocampus of VaD mice. In vitro experiments performed on hippocampal neurons demonstrated that miR-9-3p negatively regulated SAP97 expression. The downregulation of MALAT1 in hippocampal neurons increased miR-9-3p and reduced SAP97, whereas miR-9-3p inhibition rescued the MALAT1 downregulation-mediated SAP97 reduction. In conclusion, the present study reported the alterations in the expression levels of MALAT1, miR-9-3p, and SAP97 in the hippocampus of VaD mice, suggesting that MALAT1 targets miR-9-3p to upregulate SAP97 in the hippocampus of mice with VaD. This work will be helpful for understanding the molecular mechanisms of VaD.
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Experimental and Therapeutic Medicine
·
2023
·Vol. 27
·期 1
·1-13
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IF 2.7
Qiankun Quan,Xinxin Ma,Ming Li,Xi Li,Haifeng Yuan
β‑Amyloid peptide (Aβ) deposition in the brain is an important pathological change in Alzheimer's disease (AD). Insulin‑degrading enzyme (IDE), which is regulated transcriptionally by peroxisome proliferator‑activated receptor γ (PPARγ), is able to proteolyze Aβ. One of the members of the MAPK family, ERK, is able to mediate the phosphorylation of PPARγ at Ser112, thereby inhibiting its transcriptional activity. Ginsenoside Rg1 is one of the active ingredients in the natural medicine ginseng and has inhibitory effects on Aβ production. The present study was designed to investigate whether ginsenoside Rg1 is able to affect the regulation of PPARγ based on the expression of its target gene, IDE, and whether it is able to promote Aβ degradation via inhibition of the ERK/PPARγ phosphorylation pathway. In the present study, primary cultured rat hippocampal neurons were treated with Aβ1‑42, ginsenoside Rg1 and the ERK inhibitor PD98059, and subsequently TUNEL staining was used to detect the level of neuronal apoptosis. ELISA was subsequently employed to detect the intra‑ and extracellular Aβ1‑42 levels, immunofluorescence staining and western blotting were used to detect the translocation of ERK from the cytoplasm to the nucleus, immunofluorescence double staining was used to detect the co‑expression of ERK and PPARγ, and finally, western blotting was used to detect the phosphorylation of PPARγ at Ser112 and IDE expression. The results demonstrated that ginsenoside Rg1 or PD98059 were able to inhibit primary cultured hippocampal neuron apoptosis induced by Aβ1‑42 treatment, reduce the levels of intra‑ and extraneuronal Aβ1‑42 and inhibit the translocation of ERK from the cytoplasm to the nucleus. Furthermore, administration of ginsenoside Rg1 or PD98059 resulted in attenuated co‑expression of ERK and PPARγ, inhibition of phosphorylation of PPARγ at Ser112 mediated by ERK and an increase in IDE expression. In addition, the effects when PD98059 to inhibit ERK followed by treatment with ginsenoside Rg1 were found to be more pronounced than those when using PD98059 alone. In conclusion, ginsenoside Rg1 was demonstrated to exert neuroprotective effects on AD via inhibition of the ERK/PPARγ phosphorylation pathway, which led to an increase in IDE expression, the promotion of Aβ degradation and the decrease of neuronal apoptosis. These results could provide a theoretical basis for the clinical application of ginsenoside Rg1 in AD.
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INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2023
·
IF 5.8
Yue-Ming Yu,Fan-Zhi Bu,Su-Su Meng,Cui-Wei Yan,Zhi-Yong Wu,Yan-Tuan Li
To emphasize the superiority of uracil (UR) in ameliorating biopharmaceutical characteristics of marine antitumor medicine cytarabine (ARA), thus gaining some innovative opinions for the exploitation of nanococrystal formulation, a cocrystal nanonization strategy is proposed by integrating cocrystallization and nanosize preparation techniques. For one thing, based on UR's unique structural features and natures together with advantages of preferential uptake by tumor cells, cocrystallizing ARA with UR is expected to improve the in vitro / vivo performances. For another, the nanonization procedure is oriented towards maintaining the long-term effective drug level. Along this route, a cocrystal of ARA with UR, viz ., ARA-UR, is successfully synthesized and then transformed into nano-cocrystal. The cocrystal structure is precisely confirmed by various methods, demonstrating that a 1:1 ARA and UR in the crystal forms cytosine-UR hydrogen-bonding interactions, thus constructing supramolecular frameworks by strong π-π stacking interplays; while the nano-cocrystal is block-shaped particles of 562.70 nm with zeta potential −33.40 mV. The properties of cocrystal ARA-UR and its nano-cocrystal in vitro / vivo are comparatively explored by theoretical calculations and experimental analyses, revealing that permeability of both is significantly increased than ARA per se . Notably, the meliorative natures of both the cocrystal and nano-cocrystal in vitro bring excellent antitumor activity , but the latter has greater strengths over the former. More notably, the nano-cocrystal can sustain effective concentration for a relatively longer time, causing lengthened retention time and better absorption in vivo . The contribution offers a fire-new dosage form of ARA for long-lasting delivery, thus filling the vacancy in nanococrystal studies about marine drugs.
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