Frontiers in Endocrinology
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2021
·
IF 5.555
Bai Yu,Du Qiang,Zhang Le,Li Ling,Wang Nana,Wu Bo,Li Ping,Li Ling
This study aims to investigate the effect of angiopoietin like 8 (ANGPTL8) on gestational diabetes mellitus (GDM) and insulin resistance (IR). The GDM model was induced by high fat diet in mice, and IR was observed. The expression and secretion of ANGPTL8 were promoted in placenta of GDM mice. IR was induced in trophoblast cell HTR-8/SVneo by treatment of high concentration of insulin, and the expression levels of ANGPTL8 were increased. Silencing of ANGPTL8 alleviated IR and decreased glucose uptake in HTR-8/SVneo cells. However, the inflammation and oxidative stress in IR cells were not restrained by ANGPTL8 knockdown. In addition, c-Jun N-terminal kinase (JNK) signaling was activated by IR, which was inhibited by silencing of ANGPTL8. The effect of ANGPTL8 knockdown on IR was attenuated by JNK antagonist, and aggravated by JNK agonist, suggesting that ANGPTL8 affected IR by regulating JNK signaling. In conclusion, we demonstrated that the silencing of ANGPTL8 ameliorated IR by inhibiting JNK signaling in trophoblast cells. These findings may provide novel insights for diagnosis and treatment of GDM in clinic.
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INDUSTRIAL & ENGINEERING CHEMISTRY RESEARCH
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2021
·
IF 3.764
Dan-Na Hu,Xiao-Jie Ju,Xing-Qun Pu,Rui Xie,Wei Wang,Zhuang Liu,Liang-Yin Chu
Self-regulating insulin controlled-release systems have gained more attention due to their advantages of timely response to blood glucose change and avoiding side effects caused by the high-frequency injection. In this paper, the temperature-responsive monomer N-isopropylacrylamide (NIPAM) and glucose-responsive monomer 3-acrylamidophenylboronic acid (AAPBA) are copolymerized and then grafted with alginate to prepare temperature/glucose dual-responsive copolymers alginate-g-P(NIPAM-co-AAPBA) (Alg-g-PNA). The temperature and glucose responsiveness under different conditions, rheological characteristics, glucose-mediated insulin release, and biotoxicity of the Alg-g-PNA copolymers are studied. The results show that the copolymer solution is in the sol state at 10 °C and insulin can be dispersed uniformly, while it turns into the gel state when the temperature rises to physiological 37 °C for in situ delivery of insulin. Due to the sensitivity to blood glucose levels, the hydrogels can quickly respond to the increase in blood glucose and undergo the gel-to-sol transition and release insulin to reduce blood glucose when the environmental blood glucose rises. Moreover, the hydrogels have good sol–gel transition reversibility in response to changes between normoglycemic and hyperglycemic levels. The cell cytotoxicity results show that the hydrogels have good biocompatibility to be a safe carrier for insulin delivery. The proposed injectable temperature/glucose dual-responsive hydrogels in this study provide a novel type of self-regulating insulin delivery systems for diabetes therapy.
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TALANTA
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2020
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IF 5.339
Xiaowei Mu,Minxing Wu,Bo Zhang,Xin Liu,Shaomei Xu,Yibing Huang,Xinghua Wang,Daqian Song,Pinyi Ma,Ying Sun
In this study, we describe the construction of an “off-on” fluorescent probe based on carbon dots (CDs) and silver nanoparticles (AgNPs) mixture for sensitive and selective detection of cysteamine . By mixing AgNPs with CDs solution, the fluorescence of CDs was significantly decreased due to the inner filter effect (IFE). Upon addition of cysteamine to the mixed aqueous of CDs and AgNPs, the silver-sulfur bond between cysteamine and AgNPs caused AgNPs to aggregate, and the quenched fluorescence of CDs could in turn be recovered. The probe was employed to quantitatively detect cysteamine, and the results showed that it could detect cysteamine in a concentration range of 2–16 μM with the detection limit of 0.35 μM (signal-to-noise ratio of 3). The detection of cysteamine spiked into bovine serum samples showed high recovery rates ranging from 95.5 to 111.7%. More importantly, the developed probe had low cytotoxicity and was successfully used for in vivo imaging of HepG2 cells.
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DYES AND PIGMENTS
·
2020
·
IF 4.613
Qingxiao An,Qinlu Lin,Xiaohui Huang,Rongju Zhou,Xin Guo,Weizhen Xu,Suyan Wang,Dong Xu,Huan-Tsung Chang
Preparation of carbon dots (C dots) with strong emission at long wavelengths is an ongoing goal to their advanced applications, especially in bioanalysis. For sensing Fe 3+ and ascorbic acid (AA), we prepared C dots with a large Stokes shift using o- phenylenediamine (OPD) as the carbon source through an electrochemical method . During the electrolysis, OPD undergoes polymerization, carbonization , and passivation at the platinum anode to form C dots. These C dots were characterized by UV–Vis spectroscopy, transmission electron microscopy , Raman spectroscopy , X-ray photoelectron spectroscopy (XPS), and FT-IR spectroscopy. They are composed of C, N, O, H elements, having a maximum of emission at 570 nm and a supreme excitation at 261 nm, with a Stokes shift of 309 nm. A new emission at 350 nm emerged with their exposure to Fe 3+ and the intensity rises upon increasing Fe 3+ , while the emission intensity at 570 nm decreases. Thus, dissimilar to the usual quenching strategy, a novel ratiometric fluorescent sensor based on the fluorescence intensity ratio (F 350 /F 570 ) of the C dots at 350 nm and 570 nm has been developed for quantitation of Fe 3+ with a limit of detection (LOD) of 0.16 μM and high selectivity toward Fe 3+ against K + , Cu 2+ , and Fe 2+ . With evidence of decreased C–N C and C–O/N–O in XPS and increased content of C O/N O and N–H, we suggested the complexation of Fe 3+ with the surface groups led to the changes in chemical bonds accounting for their optical property variation. Furthermore, AA can quench the fluorescence of C dots at 570 nm and Fe 3+ -treated C dots (incubated with 50 μM Fe 3+ ) at 350 nm by a static mechanism. Accordingly, two assays toward AA were developed with LODs of 0.12 μM and 0.32 μM by using C dots and Fe 3+ -treated C dots, respectively. Especially, both AA assays exhibited excellent selectivity under various substances including those with strong reducing ability such as pyrogallic acid, sodium citrate, tea polyphenol, and dithiothreitol. The applications of the assays were validated with the quantitation of Fe 3+ in urine and AA in beverages. Electrochemical method is a significant approach to develop novel C dots even using the same carbon sources as in other methods.
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JOURNAL OF SOLID STATE CHEMISTRY
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2020
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IF 2.726
Yumei Xiao,Dongning Liu,Cheng Liu,Yongchao Wang,Cuijuan Wang
Curcumin (CCM) is a natural ingredient with anti-cancer activity. However, the application of CCM is limited in clinical medicine due to its high hydrophobicity and low bioavailability. Hence, it is necessary for development of a feasible strategy for efficient drug delivery and cancer cell-selective targeting. In recent years, nano-scaled metal-organic frameworks (NanoMOFs) have received much attention as an attractive drug delivery carrier due to their unique features of their various sizes, adjustable pore structures , high stability, and easy surface modification. Here, we report a novel composite nanomaterial (denoted as ZIF-8&α-lip) for CCM loading by one-pot method. This synthetic method is simple and rapid, and the final product (CCM@ZIF-8&α-lip) can be obtained within 20 min. In addition, the obtained CCM@ZIF-8&α-lip shows greater growth inhibition of HepG2 cells in comparison with CCM@ZIF-8. Therefore, ZIF-8&α-lip can be used as an ideal drug carrier and propose a new strategy to improve nanoMOFs performance for efficient drug delivery.
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Food Bioscience
·
2020
·
IF 3.067
Xiao-Hui Yao,Yu-Shi Shen,Run-Ze Hu,Ming Xu,Jia-Xing Huang,Chen-Xi He,Fu-Liang Cao,Yu-Jie Fu,Dong-Yang Zhang,Wei-Guo Zhao,Li Liu,Tao Chen
Mulberry is a traditional crop that has been grown in China for thousands of years. While leaves and fruits of the mulberry have been consumed, mulberry seed use has been less extensive. The goal of this study was to investigate the value of the seeds. Seven cultivars of mulberry were investigated. Oil was extracted from seeds, and the oil content was determined. The primary components of the oils were analyzed using gas chromatography . It was found that all the mulberry cultivars contained high linoleic acid contents, suggesting that mulberry seed may be a potential resource of linoleic acid. The total phenolic and flavonoid contents were also compared among different mulberry seed oils . The physical and chemical parameters, as well as the antioxidant activity of the mulberry seed, were determined. Principal component analysis indicated that the ferric ion reducing antioxidant power (FRAP) and 2,2-diphenyl-1-picrylhydrazyl free radical-scavenging activity (DPPH) of mulberry seed oil may be due to high phenolic compounds and linoleic acid. The cultivars Dongsheng, Fengtian, and Guisang had the highest antioxidant activities (FRAP, DPPH), and it was proposed that these cultivars would produce the highest quality oil for use as an ingredient for healthcare or functional food use.
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PEDIATRIC HEMATOLOGY AND ONCOLOGY
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2020
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IF 1.232
Ju Yang,Ping Liu,Dan Ma,Peng Zhao,Yan Zhang,Yinghao Lu,Yanju Li,Yi Huang,Ying Chen,Jishi Wang
Development of chemo‑resistance is ultimately responsible for treatment failure and relapse in B-cell acute lymphoblastic leukemia (B-ALL). However, the mechanism underlying glucocorticoid (GC) resistance remains unclear. This study was performed to identify GC resistance-related genes using the transcriptome chip from the GEO database, and preliminarily analyze drug resistance mechanism in B-ALL. Here, we found that ANXA5 expression was upregulated in B-ALL cells and high-level ANXA5 was associated with dexamethasone (DEX) resistance. Then, small interfering RNA (siRNA) was designed to silence ANXA5 expression in the B-ALL cell lines, and the apoptotic rate of cells treated with DEX was detected by flow cytometry. As a result, cell apoptosis was dramatically promoted in B-ALL cells following silencing of ANXA5 and DEX administration versus that in ANXA5-silenced alone or DEX-treated alone cells. It was further found that down-regulation of ANXA5 in B-ALL cells significantly increased the relative amount of cleaved Caspase 3 and Caspase 9 induced by DEX. Collectively, inhibition of ANXA5 gene expression may represent a novel method to restore the sensitivity of treatment-resistant B-ALL tumors to GC-induced cell death, which is of important clinical significance to overcome drug resistance associated with B-ALL.
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DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY
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2020
·
IF 2.365
Xuwang Pan,Shourong Liu,Liping Ju,Jianjun Xi,Ruoyu He,Yanmei Zhao,Rangxiao Zhuang,Jinsong Huang
Objective The objective of this study was to prepare the liver targeting drug delivery system (TDDS) of artesunate (ART)-loaded polyethylene glycol (PEG)-poly(d,l-lactic-co-glycolic) acid (PLGA) nanoparticles (NPs) modified by glycyrrhetinic acid (GA), and evaluate its in vitro cytotoxicity.Significance The GA-PEG-PLGA-ART NPs enhanced the in vitro cytotoxicity on HCC cell lines. The development of GA-PEG-PLGA NPs will greatly push the clinical applications of ART as a novel anticancer drug.Methods The NPs were prepared using solvent evaporation method, and the formulation was optimized through an orthogonal design. In addition, physical properties were determined, including particle size, polydispersity index (PDI), zeta potential (ZP), morphology, drug loading capacity (LC) and encapsulation efficiency (EE), and in vitro drug release. Moreover, the in vitro cytotoxicity of NPs with three human cancer cell lines viz. HepG2, Hep3B, and SMCC-7721 was conducted using the SRB assay. Additionally, lyophilization was conducted to improve the long-term physical stability.Results The GA-PEG-PLGA-ART NPs have spherical shape, small particle size (around 88 nm) with a narrow size distribution (PDI < 0.3), high drug LC (up to 59.3 ± 1.65%), and high EE (up to 73.13 ± 5.17%). In vitro drug release behavior showed that drugs were released from NPs in a sustained and controlled release pattern. Cytotoxicity study indicated the NPs achieved lower cancer cell survival fraction. The GA-PEG-PLGA NPs freeze-dried with 3% (w/v) of mannitol showed better effect on long-term physical stability.Conclusion The GA-PEG-PLGA-ART NPs appear as a potential liver targeted intracellular delivery platform for ART.
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JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
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2020
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IF 3.209
Chunhe Yu,Dongmiao Qin,Xiaohua Jiang,Xiangfei Zheng,Biyang Deng
In this work, fluorescent N-doped carbon quantum dots (N-CQDs) have been synthesized by simple hydrothermal heating of natural osmanthus fragrans, without any toxic ingredients or surface chemical modifications. The N-CQDs possess a high quantum yield of 21.9 %, outstanding blue fluorescence, good water dispersity, and excellent optical stability. Because the favorable inner filter effect (IFE) between N-CQDs and quercetin (QT) occurs, the addition of QT to N-CQDs can cause their fluorescence quenching. When Al 3+ was added to the N-CQDs/QT system solution, it was found that the inhibition of IFE leads to the fluorescence intensity of N-CQDs/QT system enhancement by virtue of a specific binding of QT to aluminum ion (Al 3+ ). Therefore, we used the N-CQDs as a novel off-on fluorescent nanosensor to detect QT and Al 3+ . Under optimal conditions, the fluorescent nanosensor can detect QT within the wide linear response in the range of 0.003−80 μmol/L with as low as 1 nmol/L detection limit. For the detection of Al 3+ , the N-CQDs/QT system showed linearity response toward Al 3+ in a range of 0.1∼100 μmol/L and the limit of detection was found at 26 nmol/L. In addition, N-CQDs have been successfully used to efficient quantification QT in human plasma and monitor Al 3+ in serum samples. Noteworthy, the N-CQDs demonstrated low toxicity toward T24 cells, which realized sensing QT and Al 3+ in the living cells.
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ACS Applied Bio Materials
·
2020
·
IF 0
Shanguo Zhang,Xiaojie Wang,Jia Man,Jianyong Li,Xiaoyang Cui,Chuanwei Zhang,Weichen Shi,Donghai Li,Song Zhang,Jianfeng Li
The protective effects of histone deacetylase (HDAC) inhibitors were highlighted in the treatment of kidney diseases, especially acute kidney injury (AKI). However, the currently available HDAC inhibitor cannot be delivered to the kidney properly because of its poor solubility in aqueous solutions. Therefore, calcium alginate (Ca-ALG) microspheres were proposed as microcarriers for the delivery of HDAC inhibitors in this study. First, Ca-ALG microspheres with high sphericity were obtained by a single-emulsion microfluidic strategy. Then, we selected suitable Ca-ALG microspheres for HDAC inhibitor loading by analyzing the swelling ratio and the release property using different parameters. Besides, thermal stimulation will change the drug release property of Ca-ALG microspheres in in vitro experiments. Furthermore, the HDAC inhibitor-loaded microspheres were delivered to the kidney by renal subcapsular injection for evaluating the treatment effects in mice with ischemia-reperfusion-induced AKI. The in vivo results showed that the HDAC inhibitor-loaded Ca-ALG microspheres could effectively reduce the renal regional inflammatory response and macrophage infiltration. Taken together, we proposed a promising therapy with an effective kidney-targeted drug delivery for the treatment of AKI.
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Drug Delivery and Translational Research
·
2021
·Vol. 12
·期 1
·167-179
·
IF 4.617
Wang Shuanghu,Tan Xueying,Zhou Quan,Geng Peiwu,Wang Jinhui,Zou Ping,Deng Aiping,Hu Jingbo
Multidrug resistance (MDR) is considered as a critical limiting factor for the successful chemotherapy, which is mainly characterized by the overexpression of ATP-binding cassette (ABC) transporter ABCB1 or ABCG2. In this study, folate-targeted polymeric micellar carrier was successfully constructed to co-delivery of doxorubicin (DOX) and SIS3 (FA/DOX/SIS3 micelles), a specific Smad3 inhibitor which sensitizes ABCB1- and ABCG2-overexpressing cancer cells to chemotherapeutic agents. The ratio of DOX to SIS3 in polymeric micelles was determined based on the anti-tumor activity against resistant breast cells. In addition, FA/DOX/SIS3 micelles exhibited a much longer circulation time in blood and were preferentially accumulated in resistant tumor tissue. Pharmacodynamic studies showed that FA/DOX/SIS3 micelles possessed superior anti-tumor activity than other DOX-based treatments. Overall, FA/DOX/SIS3 micelles are a promising formulation for the synergistic treatment of drug-resistant tumor. Graphical abstract
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DRUG DEVELOPMENT RESEARCH
·
2020
·Vol. 82
·期 3
·404-411
·
IF 1.902
Xiaolong Sun,Xu Wang,Zhenyu Zhao,Jing Chen,Cheng Li,Gang Zhao
Diabetic foot ulcer (DFU) is an invariably common complication of diabetes, characterized by delayed wound healing process and increased inflammation. Evidence has indicated that paeoniflorin exerts an anti-inflammatory effect in diabetic retinopathy. The current work was aimed to investigate the effect of paeoniflorin on inflammation and wound healing in DFU. DFU rat models by streptozotocin and skin biopsy punch, as well as high glucose-treated human immortalized keratinocytes (HaCaT) were established. Levels of blood glucose, wound contraction and proinflammatory cytokine were detected after paeoniflorin administration. Several essential targets associated with the NF-κB and Nod-like receptor protein-3 (NLRP3) signaling pathways were examined. Results showed markedly down-regulation of interleukin (IL)-1β, IL-18 and tumor necrosis factor-alpha in paeoniflorin-treated DFU rats. Paeoniflorin decreased the expression levels of chemokine receptor CXCR2, nuclear NF-κB and p-IκB (Ser36), as well as increased IκB level. Histological analysis and immunostaining showed lower inflammatory cells with decreased NLRP3 and cleaved caspase-1 levels following paeoniflorin treatment. Further in vitro evidence confirmed that paeoniflorin efficiently inhibited NLRP3 and NF-κB-mediated inflammation in DFU by inhibiting CXCR2. These findings are suggestive of greatly attenuated wound inflammation and better wound healing in paeoniflorin-treated DFU rats. Our study demonstrates that paeoniflorin is a potential therapeutic agent for DFU.
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