Scientific Reports
·
2022
·Vol. 12
·期 1
·1-11
·
IF 4.996
Wan Yiting,Gu Cancan,Kong Jueying,Sui Jin,Zuo Ling,Song Yanhua,Chen Jing
Endometriosis (EMs) is one of the most frequent diseases of reproductive-age women and is characterized by the growth of endometrial tissues beyond the uterus. The enhanced proliferative and migratory potential of endometrial stromal cells (ESCs) plays an important role in the progression of EMs. Mounting studies have demonstrated that long noncoding RNAs (lncRNAs) exert an important role in regulating the development and progression of EMs. Given the aberrant expression of lncRNA ADAMTS9-AS1 in ectopic endometrium (ecEM), we investigated the biological effect of ADAMTS9-AS1 on ESC proliferation and migration and explored the underlying mechanism. The current data showed that ADAMTS9-AS1 expression was significantly upregulated in ecEM compared with eutopic endometrium (euEM) in patients with EMs and in a murine model of EMs. Functionally, ADAMTS9-AS1 knockdown in ectopic ESCs (EESCs) decreased cell viability and migration, whereas ADAMTS9-AS1 overexpression in normal ESCs (NESCs) enhanced cell viability and migration. More importantly, the effect of ADAMTS9-AS1 inhibition on decreasing ESC viability was significantly blocked by ferrostatin-1 (Fer-1, a ferroptosis inhibitor), and ADAMTS9-AS1 overexpression repressed erastin (a ferroptosis activator)-induced cell death. Furthermore, the regulatory role of ADAMTS9-AS1 in ferroptosis was defined and evidenced by increased reactive oxygen species (ROS) levels and malonyl dialdehyde (MDA) content and decreased expression of glutathione peroxidase 4 (GPX4) after ADAMTS9-AS1 inhibition. Mechanistically, ADAMTS9-AS1 functioned as a competing endogenous RNA (ceRNA) by sponging miR-6516-5p to derepress the expression of GPX4, the critical repressor of ferroptosis. Taken together, these results demonstrate that upregulated ADAMTS9-AS1 accelerates ESC proliferation and migration by regulating miR-6516-5p/GPX4-dependent ferroptosis and may be a potential target for the treatment of EMs.
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高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2020
·Vol. 18
·期 1
·1-14
·
IF 6.518
Ma Xi-Xi,Xu Jing-Liang,Jia Yi-Yang,Zhang Ya-Xuan,Wang Wei,Li Chen,He Wei,Zhou Si-Yuan,Zhang Bang-Le
Background Gene therapy remains a significant challenge due to lots of barriers limiting the genetic manipulation technologies. As for non-viral delivery vectors, they often suffer insufficient performance due to inadequate cellular uptake and gene degradation in endosome or lysosome. The importance of overcoming these conserved intracellular barriers is increasing as the delivery of genetic cargo. Results A surface-functionalized non-viral vector involving the biomimetic mannitol moiety is initiated, which can control the cellular uptake and promote the caveolae-mediated pathway and intracellular trafficking, thus avoiding acidic and enzymatic lysosomal degradation of loaded gene internalized by clathrin-mediated pathway. Different degrees of mannitol moiety are anchored onto the surface of the nanoparticles to form bio-inspired non-viral vectors and CaP-MA-40 exhibits remarkably high stability, negligible toxicity, and significantly enhanced transgene expression both in vitro and in vivo. Conclusions This strategy highlights a paradigmatic approach to construct vectors that need precise intracellular delivery for innovative applications.
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BMC Veterinary Research
·
2022
·Vol. 18
·期 1
·1-9
·
IF 2.792
Chen Zixiu,Zhao Junhong,Yan Yongjing,Zhang Lei,Du Lijie,Liu Xiang,Cao Manxiu,Wang Cangyu,Tang Yue,Li Haihong
Background Eccrine sweat glands (ESGs) and hair follicles (HFs) are the prominent skin appendages regulating human body temperature. C57BL/6 mice and Sprague–Dawley (SD) rats are the most commonly used model animals for studying ESGs and HFs. Previous studies have shown the distribution of ESGs and HFs in volar hindfeet of C57BL/6 mice, but there are few or no reports on the distribution of ESGs and HFs in volar forefeet of C57BL/6 mice and volar feet of SD rats. Here, we investigated the differential distribution and genetic determination of ESGs and HFs in the volar skin of C57BL/6 mice and SD rats through gross observation, iodine-starch sweat test, double staining with Nile Blue A and Oil Red O, hematoxylin and eosin (HE) staining, double immunofluorescence staining of LIM Homeobox 2 (LHX2)/Na + -K + -ATPase α1(NKA) or LHX2/Na + -K + -2Cl - cotransporter 1 (NKCC1), and qRT-PCR detection of ESG-related gene Engrailed 1 ( En1 ) and HF-related gene LHX2 . Results The results showed ESGs but no HFs in the footpads of C57BL/6 mice and SD rats, both ESGs and HFs in the inter-footpads (IFPs) of C57BL/6 mice, and neither ESGs nor HFs in the IFPs of SD rats. The relative quantitative change in En1 was consistent with the differential distribution of ESGs, and the relative quantitative change of LHX2 was consistent with the differential distribution of HFs. Conclusion C57BL/6 mice and SD rats had their own characteristics in the distribution of ESGs and HFs in the volar skin, and researchers should choose mice or rats, and even forefeet or hindfeet as their research object according to different purposes. The study provides a basis for selection of optimal animal models to study development, wound healing and regeneration of skin appendages.
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高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2021
·Vol. 19
·期 1
·1-21
·
IF 10.435
Wang Tian-Long,Zhou Zi-Fei,Liu Jun-Feng,Hou Xiao-Dong,Zhou Zhi,Dai Yun-Lu,Hou Zhi-Yong,Chen Feng,Zheng Long-Po
Background Skin injury and the resultant defects are common clinical problems, and usually lead to chronic skin ulcers and even life-threatening diseases. Copper, an essential trace element of human body, has been reported to promote the regeneration of skin by stimulating proliferation of endothelial cell and enhance angiogenesis. Results Herein, we have prepared a new donut-like metal–organic frameworks (MOF) of copper-nicotinic acid (CuNA) by a simple solvothermal reaction. The rough surface of CuNA is beneficial for loading/release basic fibroblast growth factor (bFGF). The CuNAs with/without bFGF are easily processed into a light-responsive composite hydrogel with GelMA, which not only show excellent mechanical properties, but also display superior biocompatibility, antibacterial ability and bioactivity. Moreover, in the in vivo full-thickness defect model of skin wound, the resultant CuNA-bFGF@GelMA hydrogels significantly accelerate the wound healing, by simultaneously inhibiting the inflammatory response, promoting the new blood vessels formation and the deposition of collagen and elastic fibers. Conclusions Considering the superior biocompatibility, antibacterial ability and bioactivity, the CuNA and its composite light-responsive hydrogel system will be promising in the applications of skin and even other tissue regeneration. Graphic abstract
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NPG Asia Materials
·
2019
·Vol. 11
·期 1
·1-18
·
IF 8.052
Liu Lili,Xiang Yi,Wang Zhen,Yang Xiaonan,Yu Xiaohua,Lu Yong,Deng Lianfu,Cui Wenguo
Loading hydrogels with bioactive agents is an important method for expanding the functional application of hydrogels. However, how to improve the local administration and slow release of drugs from a hydrogel is a challenge when using hydrogels loaded with drugs. In this paper, we first developed adhesive liposomes (A-LIP) loaded with BMP-2. Then, we incorporated the A-LIP into PEG hydrogels based on the coordinated cross-linking principle of SH-PEG and Ag + , fabricating an injectable, antibacterial and self-healing multifunctional drug delivery system. The adhesive lipo-hydrogel (A-LIP-PEG) fabricated by mixing PEG hydrogels and adhesive liposomes can be locally injected into an osteoporotic fracture and bone marrow cavity, where A-LIP-PEG can release adhesive liposomes that adhere to the bone injury area and promote bone reconstruction. Based on the principle of electrostatic attraction, tissue nonspecific A-LIP were fabricated by grafting octadecylamine onto liposomes. Because of the coordination and cross-linking of thiolated polyethylene (SH-PEG) and Ag + , the A-LIP-PEG showed excellent injectability and self-healing properties; further, because of the presence of Ag + , the A-LIP-PEG showed effective inhibition of S. aureus and Escherichia coli . The liposomes released by the A-LIP-PEG were able to adhere to tissue. In vitro studies showed that A-LIP-PEG significantly promoted osteogenic differentiation and had no significant effect on cell proliferation. Compared with common lipo-hydrogel (LIP-PEG), the A-LIP-PEG had better tissue adhesion in vivo, which led to better osteogenic differentiation and faster local bone remodeling of osteoporotic fractures in rats. This research developed a novel hydrogel system with adhesive liposomes to expand the application of hydrogels.
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JOURNAL OF NANOBIOTECHNOLOGY
·
2017
·Vol. 15
·期 1
·1-17
·
IF 4.946
Wang Jingnan,Tan Jiayun,Luo Jiahao,Huang Peilin,Zhou Wuyi,Chen Luming,Long Lingli,Zhang Li-ming,Zhu Banghao,Yang Liqun,Deng David Y. B.
Background Diabetic retinopathy is the most common complication in diabetic patients relates to high expression of VEGF and microaneurysms. Scutellarin (Scu) turned out to be effective against diabetes related vascular endothelial cell dysfunction. However, its clinical applications have been limited by its low bioavailability. In this study, we formulated and characterized a novel intestinal target nanoparticle carrier based on amphiphilic chitosan derivatives (Chit-DC-VB12) loaded with scutellarin to enhance its bioavailability and then evaluated its therapeutic effect in experimental diabetic retinopathy model.Results Chit-DC-VB12 nanoparticles showed low toxicity toward the human colon adenocarcinoma (Caco-2) cells and zebra fish within concentration of 250 μg/ml, owing to good biocompatibility of chitosan. The scutellarin-loaded Chit-DC-VB12 nanoparticles (Chit-DC-VB12-Scu) were then prepared by self-assembly in aqueous solution. Scanning electron microscopy and dynamic light scattering analysis indicated that the Chit-DC-VB12-Scu nanoparticles were spherical particles in the sizes ranging from 150 to 250 nm. The Chit-DC-VB12-Scu nanoparticles exhibited high permeation in Caco-2 cell, indicated it could be beneficial to be absorbed in humans. We also found that Chit-DC-VB12 nanoparticles had a high cellular uptake. Bioavailability studies were performed in Sprague–Dawley rats, which present the area under the curve of scutellarin of Chit-DC-VB12-Scu was two to threefolds greater than that of free scutellarin alone. Further to assess the therapeutic efficacy of diabetic retinopathy, we showed Chit-DC-VB12-Scu down-regulated central retinal artery resistivity index and the expression of angiogenesis proteins (VEGF, VEGFR2, and vWF) of retinas in type II diabetic rats.Conclusion sChit-DC-VB12 nanoparticles loaded with scutellarin have better bioavailability and cellular uptake efficiency than Scu, while Chit-DC-VB12-Scu nanoparticles alleviated the structural disorder of intraretinal neovessels in the retina induced by diabetes, and it also inhibited the retinal neovascularization via down-regulated the expression of angiogenesis proteins. In conclusion, the Chit-DC-VB12 nanoparticles enhanced scutellarin oral delivery efficacy and exhibited potential as small intestinal target promising nano-carriers for treatment of type II diabetes induced-retinopathy.
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Cell Death Discovery
·
2020
·Vol. 6
·期 1
·1-13
·
IF 4.114
Zheng Tao,Zhao Chuchu,Zhao Baowen,Liu Hanruo,Wang Shijian,Wang Liyuan,Liu Ping
Macular corneal dystrophy (MCD) is ascribed to mutations in the carbohydrate sulfotransferase ( CHST6 ) gene affecting keratan sulfate (KS) hydrophilicity and causing non-sulfated KS to precipitate in keratocytes and the corneal stroma. We investigated roles for inflammatory responses in MCD pathogenesis by examining the lysosomal-autophagy pathway and activation of pyroptosis in MCD keratocytes. Normal and lesioned keratocytes were obtained from MCD patients undergoing corneal transplantation. The keratocytes were subjected to gene sequencing, RT-PCR, western blotting, transmission electron microscopy, histological staining, induction and inhibition assays of autophagy and pyroptosis, CCK-8 and LysoTracker Green DND-26 labeling, and flow cytometry. A novel homozygous MCD mutation was identified in a family from Northeast China; the mutation was distinguished by cytoplasmic vacuolation, cell membrane disruption, electron dense deposits, and deposition of a band of Periodic acid-Schiff and Alcian blue-positive material in the keratocytes and stroma layer. KS protein levels were decreased, expression of p62 and LC3-II proteins was enhanced, cathepsin D expression was declined and the LysoTracker Green DND-26 signal was dramatically reduced in MCD keratocytes. Bafilomycin-A1 treatment significantly increased caspase-1 and Pro-IL-1β expression in normal and MCD keratocytes. Nod-like receptors pyrins-3 (NLRP3), caspase-1, Pro-IL-1β, and IL-1β levels were pronouncedly elevated in cells exposed to H 2 O 2 . Ac-YVAD-CMK treatment reversed this expression in normal and MCD keratocytes. Suppression of the autophagic degradation of non-sulfated KS by impaired autophagic flux in MCD keratocytes triggers pyroptosis. Amelioration of impaired autophagy and restraint of pyroptosis may, therefore, have therapeutic efficacy in the treatment of MCD.
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Nature Communications
·
2021
·Vol. 12
·期 1
·1-12
·
IF 14.919
Cheng Mengzhu,Wang Lihong,Zhou Qing,Chao Daiyin,Nagawa Shingo,He Ding,Zhang Jiazhi,Li Hui,Tan Li,Gu Zhenhong,Huang Xiaohua,Yang Zhenbiao
Trivalent rare earth elements (REEs) are widely used in agriculture. Aerially applied REEs enter leaf epidermal cells by endocytosis and act systemically to improve the growth of the whole plant. The mechanistic basis of their systemic activity is unclear. Here, we show that treatment of Arabidopsis leaves with trivalent lanthanum [La(III)], a representative of REEs, triggers systemic endocytosis from leaves to roots. La(III)-induced systemic endocytosis requires AtrbohD-mediated reactive oxygen species production and jasmonic acid. Systemic endocytosis impacts the accumulation of mineral elements and the development of roots consistent with the growth promoting effects induced by aerially applied REEs. These findings provide insights into the mechanistic basis of REE activity in plants.
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JOURNAL OF NANOBIOTECHNOLOGY
·
2018
·Vol. 16
·期 1
·1-14
·
IF 5.294
Qin Yanxia,Chen Kui,Gu Weihong,Dong Xinghua,Lei Ruihong,Chang Yanan,Bai Xue,Xia Shibo,Zeng Li,Zhang Jiaxin,Ma Sihan,Li Juan,Li Shan,Xing Gengmei
Background Tumor metastasis is the primary cause of mortality in cancer patients. Migratory breast cancer cells in lymphatic and blood vessels seek new sites and form metastatic colonies in the lung and bone, and then these cancer cells often wreak considerable havoc. With advances in nanotechnology, nanomaterials and nanotechnologies are widely applied in tumor therapy. In this paper, small size fullerenol nanoparticles, which are separated by isoelectric focusing electrophoresis (IFE) for discrepancy of isoelectric point (pI), are used in the study of tumor metastasis.Results In this study, the commendable inhibition of tumor metastasis was uncovered by intravenous injection of purified fullerenol fraction with special surface charge and functional groups, which was separated by IFE for discrepancy of pI. By investigating the actin dynamics in several cancer cell lines, we found these small size fullerenol nanoparticles disturbed actin dynamics. Young’s modulus detection and cell migration assays revealed that fullerenol lowered stiffness and restrained migration of breast cancer cells. Filopodia, the main supporting structures of actin bundles, are important for cell motility and adhesion. Scanning electron microscopy showed that fullerenol reduced the number and length of filopodia. Simultaneously, the inhibition of integrin to form clusters on filopodias, which was likely induced by reorganizing of actin cytoskeleton, impacted cancer cell adhesion and motility.Conclusion sWith intravenous injection of these fullerenol nanoparticles, tumor metastasis is well inhibited in vivo. The underlying mechanism most likely to be attributed to the effect of fullerenol nanoparticles on disturbing actin dynamics. With the disordered actin fiber, cell function is varied, including decreased cell stiffness, reduced filopodia formation, and inactivated integrin.
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MICROCHIMICA ACTA
·
2017
·Vol. 184
·期 5
·1305-1313
·
IF 4.58
Zhou Lili,Wang Jian,Chen Zhongping,Li Junlong,Wang Ting,Zhang Zhang,Xie Guoming
MicroRNAs (miRNAs) play a considerable role in cancer occurrence and development, and have been identified as promising noninvasive biomarkers. The authors describe a voltammetric method for the determination of the cancer biomarker microRNA-21 (miRNA). It is based on a combination of a universal DNA signal transducer and isothermal target recycling amplification. A hairpin capture probe is bound to the target miRNA to form a duplex structure and to create a toehold in the transducer for initiating the target recycling amplification reaction. In contrast to traditional capture probes, a mismatched site is introduced to improve its ability to capture the target. In order to reduce the complex design procedures of the sequence and widen the applicability of this method, a signal transducer is introduced. Under optimal conditions, response to target miRNA is linear in the 0.5 to 2000 pM concentration range, with a 56 fM. detection limit (at an S/N ratio of 3). In order to characterize the process of target recycling and the stepwise modification of the electrode, real-time fluorescence, agarose gel electrophoresis, cyclic voltammetry, electrochemical impedance spectroscopy and chronocoulometry were used. The results indicate that this isothermal target recycling amplification results in an electrochemical biosensing scheme with wide potential for sensing other bioanalytes.
Schematic illustration of the electrochemical biosensing platform for miRNA-21 detection based on isothermal target recycling amplification and DNA signal transducer triggered strategy.
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MICROCHIMICA ACTA
·
2019
·Vol. 186
·期 8
·1-10
·
IF 5.479
Li Xiaohua,Wang Shanshan,Meng Yuchan,Wang Xiao,Zhang Yue,Hun Xu
Copper(II) polyphthalocyanine (CuPPc) was combined with graphitic carbon nitride (g-C 3 N 4 ) to form a heterojunction with enhanced photoelectrochemical (PEC) signal. A sensitive PEC method was developed for determination of ractopamine based on a PEC inner filter effect between gold nanoparticles (AuNPs) and the g-C 3 N 4 /CuPPc. A gold electrode was modified with g-C 3 N 4 /CuPPc and the DNA was linked to the AuNPs. Initially, the PEC signal is weak due to the inner filter effect between the AuNPs and g-C 3 N 4 /CuPPc. In the presence of ractopamine, it interacts with the aptamer and the complementary chain (C chain) is released. This triggers the entropy-driven cyclic amplification and results in the release of the substrate B chain (SB chain) from three-dimensional DNA stabilizer. The probe is released from the electrode due to the interaction of probe DNA and the SB chain. As a result, the PEC signal increases linearly in the 0.1 pmol·L −1 to 1000 pmol·L −1 ractopamine concentration range. The detection limit is 0.03 pM, and the relative standard deviation is 3.4% (at a 10 pmol·L −1 level; for n = 11). The method has been successfully applied to the determination of ractopamine in pork samples.
Schematic presentation of detection method based on PEC inner filter effect between AuNPs and the g-C 3 N 4 /CuPPc being fabricated for ractopamine. 3D DNA was used as stabilizer to decrease the PEC blank signal.
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MICROCHIMICA ACTA
·
2014
·Vol. 182
·期 5
·1123-1129
·
IF 3.719
Wang Wenting,Wang Wei,Davis Jason J.,Luo Xiliang
We describe an aptasensor for the determination of dopamine in human serum and with ultrahigh sensitivity and selectivity. The sensor is based on a nanocomposite consisting of reduced graphene oxide (rGO) and the conducting polymer poly(3,4-ethylenedioxythiophene) (PEDOT). The PEDOT/rGO interface was prepared by electrochemical polymerization of EDOT using graphene oxide as the dopant which is later electrochemically reduced to form rGO. Subsequent covalent modification of the high surface area composite with a selective aptamer enables highly sensitive and selective detection by differential pulse voltammetry. The calibration plot established at a working voltage of 160 mV displays a linear response in the 1 pM to 160 nM concentration range and an unprecedented detection limit of 78 fM. The sensor is fairly selective in not responding to common interferents, and is reusable after regeneration with a 7 M solution of urea. It was successfully applied to (spiked) serum samples and gave recoveries ranging from 98.3 to 100.7 %.
A highly sensitive and selective biosensor for dopamine was developed based on an aptamer-modifed conducting polymer (PEDOT) doped with reduced graphene oxide.
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