ACS Applied Bio Materials
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2020
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IF 0
Qin Wang,Liming He,Donghao Fan,Wenlang Liang,Xiaochen Wang,Jiyu Fang
Environment-responsive drug delivery is a promising approach for tailoring the drug release in drug therapy. In this study, we develop lipid tubules by the self-assembly of 1,2-bis(tricosa-10,12-diynoyl)-sn-glycero-3-phosphocholine (DC8,9PC). These lipid tubules are capable of encapsulating hydrophobic dexamethasone (Dex) and hydrophilic dexamethasone sodium phosphate (DSP) simultaneously. In vitro studies show that the lipid tubules can be internalized by cells with no significant toxicity. We find that phospholipase (PLA2) is able to slowly digest the lipid tubules and trigger the sustained release of Dex and DSP. After being subcutaneously administrated to the inflammatory sites of arthritic rats, we show that a single dose of drug-loaded lipid tubules can remarkably inhibit the degree of joint swelling at the inflammatory sites and suppress the content of proinflammatory cytokines in inflamed tissues for a long time by this sustained release of both Dex and DSP triggered by the highly expressed PLA2 at the inflamed sites. Our results highlight the potential of using PLA2-responsive lipid tubules as on-demand carriers for treating inflammatory diseases.
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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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Nature Communications
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2020
·Vol. 11
·期 1
·1-12
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IF 12.121
Wang Rui,Shi Miusi,Xu Feiyan,Qiu Yun,Zhang Peng,Shen Kailun,Zhao Qin,Yu Jiaguo,Zhang Yufeng
Titanium implants have been widely used in bone tissue engineering for decades. However, orthopedic implant-associated infections increase the risk of implant failure and even lead to amputation in severe cases. Although TiO 2 has photocatalytic activity to produce reactive oxygen species (ROS), the recombination of generated electrons and holes limits its antibacterial ability. Here, we describe a graphdiyne (GDY) composite TiO 2 nanofiber that combats implant infections through enhanced photocatalysis and prolonged antibacterial ability. In addition, GDY-modified TiO 2 nanofibers exert superior biocompatibility and osteoinductive abilities for cell adhesion and differentiation, thus contributing to the bone tissue regeneration process in drug-resistant bacteria-induced implant infection.
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MICROCHIMICA ACTA
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2020
·Vol. 187
·期 11
·1-12
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IF 6.232
Yang Huiyi,He Qiyi,Chen Yingshan,Shen Ding,Xiao Huanxin,Eremin Sergei A.,Cui Xiping,Zhao Suqing
Platinum nanoflowers (PtNFs) were utilized in a competitive enzyme-linked immunosorbent assay (ELISA) and in a lateral flow immunoassay (LFIA) for superior peroxidase-like activity and intense brown color, respectively. PtNFs were linked to the polyclonal antibody (pAb) to form the pAb-PtNFs probes for the dual immunoassay. Based on optimized pAb-PtNF probes, both enzyme-linked immunosorbent assay (PtNFs-ELISA) and lateral flow immunoassay (PtNFs-LFIA) perform very well. The absorbance at 450 nm decreases linearly in the DHEA concentration range 2.1 to 118.1 ng mL −1 , and the limit of detection is 1.3 ng mL −1 and the IC 50 value is 15.7 ng mL −1 of PtNFs-ELISA. The visual cut-off value of PtNFs-LFIA is 10.0 ng mL −1 . The average recoveries from spiked samples range from 95.0 to 108.9% with a coefficient of variation below 12.2%. Excellent recoveries and correlation between the two methods were observed. Furthermore, the designed immunosensors exhibited good selectivity, confirming a broad development prospect in DHEA monitoring.
Graphical Abstract
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ANALYTICA CHIMICA ACTA
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2020
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IF 5.977
Jiating Zheng,Shuyao Huang,Yuanjun Tong,Songbo Wei,Guosheng Chen,Siming Huang,Gangfeng Ouyang
The secretion disorder of sex hormones is the source that leads to the occurrence of many diseases such as polycystic ovarian syndrome (PCOS), hyperandrogenism and so on. There exist physiological changes in human body when slight fluctuations in concentrations of sex hormones happen. Therefore, it’s of great significance for accurate detection of sex hormones in human body. In this work, TpPa-1 COF solid-phase microextraction (SPME) fiber was prepared using high-efficient in-situ synthesis strategy and coupled with HPLC-MS/MS to detect three sex hormones, including Progesterone (P), testosterone (T) and dehydroepiandrosterone (DHEA) in human serum. The thickness of the coating reached 7 μ m within 2 h. Under the optimal conditions, the established method presented low limit of detections (LODs, ≤ 0.75 ng/mL), wide linear ranges (0.100–100 ng mL −1 ) and good reproducibility, and three sex hormones (T, P, DHEA) were successfully detected and quantified in human serum. In conclusion, the established SPME method presented high-efficient fiber preparation and good analytical performances of sex hormone detection, therefore was in great potential for application in clinical.
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CHEMICAL ENGINEERING JOURNAL
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2020
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IF 10.652
Youfang Huang,Yanyun Li,Qing Luo,Xiaojia Huang
Efficient capture of glucocorticoids (GCs) at ultra-trace levels in environmental waters is not an easy task due to the abundant hydrophilic groups in their molecules and complexity of sample matrices. In this study, by means of one-step hydrothermal strategy, a functional groups-rich magnetic nanocomposite (MNC) was prepared using amino-derivatized carbon nanotubes and 1-formylimidazole modified graphene oxide as functional reagents. The characterization results indicated that the obtained nanocomposite displayed satisfying saturation magnetism and could be employed to quickly extract GCs under the format of magnetic solid phase extraction (MSPE). In addition, the prepared MNC presented notable capture ability to studied GCs through multiple interactions such as π-π, hydrophobic, H-bonding and dipole-dipole forces. Under the optimized parameters, highly sensitive method based on MNC/MSPE and high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was developed to quantify ultra-trace levels of GCs in a variety of environmental waters. Low limits of detection (0.0075–0.16 ng/L), wide linearity (0.05–1000 ng/L) and excellent precision (RSDs < 10%) were achieved. The possible extraction mechanism was also investigated. Combining with isotope internal standard calibration curve approach, the suggested MNC/MSPE-HPLC-MS/MS approach was applied to measure low contents of thirteen GCs in river water, lake water, sea water and effluent from treatment plant, and good fortified recoveries (79.7–120%) and reproducibility (RSDs below 10%) were obtained.
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NUCLEIC ACIDS RESEARCH
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2020
·Vol. 48
·期 17
·9986-9994
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IF 11.502
Sun Yuhuan,Zhao Chuanqi,Cui Tingting,Qin Hongshuang,Niu Jingsheng,Ren Jinsong,Qu Xiaogang
Telomeric DNA, whose length homeostasis is closely correlated with immortality of cancer cells, is regarded as a molecular clock for cellular lifespan. Regarding the capacity in forming G-quadruplex, G-rich 3′-overhang (G-overhang) has been considered as an attractive anticancer target. However, it is still challenging to precisely target telomeric G-overhang with current ligands because of the polymorphism of G-quadruplexes in cells. Herein, we construct a telomeric G-overhang-specific near-infrared-traceable DNA nano-hydrolase, which is composed of four parts: (i) dexamethasone for targeting cell nuclei; (ii) complementary DNA for hybridizing with G-overhang; (iii) multinuclear Ce(IV) complexes for hydrolyzing G-overhang; and (iv) upconversion nanoparticles for real-time tracking. The multivalent targeted DNA nano-hydrolase can be traced to precisely digest telomeric G-overhang, which contributes to telomeric DNA shortening and thereby causes cell aging and apoptosis. The anticancer treatment is further proved by in vivo studies. In this way, this design provides a telomeric G-overhang-specific eradication strategy based on a non-G-quadruplex targeting manner.
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JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
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2020
·Vol. 25
·期 2
·1140-1150
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IF 4.486
Jie Xu,Dazhi Chen,Lanling Jin,Zhengkang Chen,Yulu Tu,Xiaozhe Huang,Feiben Xue,Jialu Xu,Mingzhuan Chen,Xiaodong Wang,Yongping Chen
Inflammation and fibrosis are major consequences of autoimmune hepatitis, however, the therapeutic mechanism remains to be investigated. USP4 is a deubiquitinating enzyme and plays an important role in tissue fibrosis and immune disease. Vialinin A is an extract from mushroom and is a specific USP4 inhibitor. However, there is lack of evidences that Vialinin A plays a role in autoimmune hepatitis. By employing S100-induced autoimmune hepatitis in mice and AML12 cell line, therapeutic mechanism of Vialinin A was examined. Inflammation was documented by liver histological staining and inflammatory cytokines. Fibrosis was demonstrated by Masson, Sirius red staining and fibrotic cytokines with western blot and real-time RT-PCR. In experimental animal, there were increases in inflammation and fibrosis as well as USP4, and which were reduced after treatment of Vialinin A. Vialinin A also reduced Rheb and phosphorylated mTOR. Moreover, in LPS-treated AML12 cells, LPS-induced USP4, inflammatory and fibrotic cytokines, phosphorylated mTOR and Rheb. Specific inhibitory siRNA of USP4 reduced USP4 level and the parameters mentioned above. In conclusion, USP4 was significantly elevated in autoimmune hepatitis mice and Vialinin A reduced USP4 level and attenuate inflammation and fibrosis in the liver. The mechanism may be related to regulation of Rheb/mTOR signalling.
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JOURNAL OF SEPARATION SCIENCE
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2020
·Vol. 43
·期 11
·2105-2114
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IF 2.878
Can Wu,Nani Wang,Pingcui Xu,Xuping Wang,Dan Shou,Yan Zhu
Cell membrane chromatography is a powerful tool for screening active components from complex matrices. New cell membrane carriers need to be developed to increase the coverage of cell membranes on the surface of stationary phases, thereby improving cell membrane chromatographic retention. In this work, we prepared polyvinyl alcohol-poly dimethyl diallyl ammonium chloride modified silica gel as a cell membrane carrier. Osteoblast cell was used as cell membrane source, which was widely used to evaluate the osteogenic activity of drugs. The new cell membrane chromatographic stationary phase was used to screen anti-osteoporosis components in Liuwei Dihuang decoction-containing serum. The chemical structures of the new modified materials were characterized by scanning electronic microscopy, Fourier transform infrared spectroscopy, and elemental analysis characterization. Compared with the common cell membrane column, the cell membrane coverage of this modified material was increased by 30%, and thus provided a stronger retention effect in positive drugs. Nineteen metabolites in rat serum samples were retained on the cell membrane chromatography and identified by ultra-high-performance liquid chromatography/time-of-flight mass spectrometry. Among those, four components (morroniside, catalpol, loganin, and acteoside) were selected for in vitro pharmacodynamics validation. They significantly increased the osteoblast proliferation. The new modified material was successfully applied to screen anti-osteoporosis components from Liuwei Dihuang Decoction-containing serum.
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2020
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IF 4.192
Suwen Liu,Xuedong Chang,Jincheng Yu,Weifeng Xu
This study aimed to determine the anti-obesity effects and mechanisms of Cerasus humilis polyphenol (CHP) in C57BL/6 obese mice and 3T3-L1 cells. High-performance liquid chromatography–electrospray ionization-tandem mass spectrometry was used for the qualitative and quantitative identification of CHP components. The obese mice, induced by feeding high-fat diet (HFD), were treated with CHP (250 mg/kg/day) by gavage for 12 weeks. Orlistat was gavaged at 15.6 mg/kg bw/day, as a positive control group. The analysis revealed that the main components of CHP were procyanidin B2, cyanidin-3-glucoside, and pelargonidin-3-glucoside. CHP dietary supplementation significantly reduced body weight and improved blood lipid measurements in HFD-fed mice (p < 0.01). Moreover, it inhibited mRNA expression of miR-122, Srebp-1c, and Cpt1a (p < 0.01) and reduced hepatic lipid deposition, as seen by hematoxylin and eosin staining. CHP downregulated the protein expression of PPARγ and C/EBPα in HFD-induced obese mice and inhibited adipocyte differentiation (p < 0.01). Compared with the HFD group, CHP supplementation had an obvious anti-inflammatory effect (decreased protein expression, such as TNF-α, IL-6, and MCP1), reducing leptin levels and TNF-α secretion in serum and cells (p < 0.01). CHP significantly inhibited the expression of miR-27a/b (53.3 and 29.9%, p < 0.01) in mice retroperitoneal white adipocytes, enhancing the expression of the target gene Prdm16 and significantly upregulating Sirt1 (105.5%, p < 0.01) compared with the HFD group. Moreover, CHP supplementation effectively improved oxidative stress (ROS, T-AOC, SOD, CAT, and GSH-Px) induced by HFD in obese mice (p < 0.01). Thus, CHP mitigates adipocyte differentiation, browning of white adipocytes, and reduction of inflammation and antioxidant activity to reduce obesity. Consequently, these results provide novel insights into the anti-obesity roles of CHP in HFD-induced obesity.
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EXPERIMENTAL CELL RESEARCH
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2020
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IF 3.383
Guangduo Zhu,Xiaowei Yang,Cheng Peng,Lei Yu,Yingjie Hao
The transplantation of bone marrow mesenchymal stem cells (BMSCs) has been found to be used as an effective therapy of intervertebral disc degeneration (IDD). However, the underlying mechanisms of BMSCs in the progress of IDD are not fully explained. In this study, we found that exosomes derived from BMSCs (BMSCs-Exos) inhibited the apoptotic rate , extracellular matrix (ECM) degradation, and fibrosis deposition in TNF-α-induced nucleus pulposus cells (NPCs). Importantly, the level of miR-532–5p was observed to be decreased in apoptotic NPCs, but abundant in BMSCs-Exos with TNF-α treatment. The results showed that BMSCs-Exos under TNF-α stimuli exerted better effects on NPCs than BMSCs-Exos, which might be mitigated by the inhibition of miR-532–5p in BMSCs-Exos. The gain-of-function results suggested that the direct overexpression of miR-532–5p in NPCs could inhibit TNF-α-induced increase of apoptotic process, activation of apoptotic proteins, imbalance of anabolism/catabolism levels, and accumulation of collagen I. In addition, RASSF5 was demonstrated to be a target of miR-532–5p. Knockdown of RASSF5 could decrease the apoptotic cells and reduce the activated apoptotic protein levels in TNF-α-induced NPCs. Overall, these data indicate that exosomes from BMSCs may suppress TNF-α-induced apoptosis, ECM degradation, and fibrosis deposition in NPCs through the delivery of miR-532–5p via targeting RASSF5. This work provides a promising therapeutic strategy for the progress of IDD.
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MEDICAL SCIENCE MONITOR
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2020
·
IF 1.918
Weidong Zhang,Jun Yu,Mengzhuo Guo,Bo Ren,Yanyan Tian,Qinggang Hu,Qun Xie,Chen Xu,Zeguo Feng
Background Glutamate (GLU) is the most excitatory amino acid in the central nervous system and plays an important role in maintaining the normal function of the nervous system. During cerebral ischemia, massive release of GLU leads to neuronal necrosis and apoptosis. It has been reported that dexmedetomidine (DEX) possesses anti-oxidant and anti-apoptotic properties. The objective of this study was to investigate the effects of DEX on GLU-induced neurotoxicity in PC12 cells. Material/Methods PC12 cells were treated with 20 mM GLU to establish an ischemia-induced injury model. Cell viability was accessed by MTT assay. MDA content and SOD activity were analyzed by assay kits. Apoptosis rate, ROS production, intracellular Ca 2+ concentration, and MMP were evaluated by flow cytometry. Western blot analysis was performed to analyze expressions of caspase-3, caspase-9, cyt-c, bax, and bcl-2. Results PC12 cells treated with GLU exhibited reduced cell viability and increased apoptosis rates, which were ameliorated by pretreatment with DEX. DEX significantly increased SOD activity, reduced content of MDA, and decreased production of ROS in PC12 cells. In addition, DEX clearly reduced the level of intracellular Ca 2+ and attenuated the decline of MMP. Moreover, DEX notably reduced expressions of caspase-3, caspase-9, cyt-c, and bax and increased expression of bcl-2. Conclusions Our findings suggest that DEX can protect PC12 cells against GLU-induced cytotoxicity, which may be attributed to its anti-oxidative property and reduction of intracellular calcium overload, as well as its ability to inhibit the mitochondria-mediated apoptotic pathway.
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