Suchergebnisse

Bo Wang,1,* Peng Li,1,* Lei Shangguan,2,* Jun Ma,3,* Kezheng Mao,4 Quan Zhang,5 Yiguo Wang,6 Zhongyang Liu,1,2 Keya Mao1 1Department of Orthopedics, Chinese PLA General Hospital, Beijing, 100853, China; 2Department of Orthopedics, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, 710032, China; 3Department of Orthopedics Trauma Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, 200003, China; 4Department of Orthopedics, Orthopedics Hospital of Zhengzhou City, Zhengzhou, Henan, 450052, China; 5Department of Orthopedics, People's Hospital of Tianjin City, Tianjin, 300121, China; 6Department of Orthopedics, Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210000, China *These authors contributed equally to this work Introduction: Failed back surgery syndrome is a situation where there is failure after lumbar surgery aimed at correcting lumbar disease that is characterized by continuous back and/or leg pain. Epidural fibrosis and adhesions are among the major causes of failed back surgery syndrome. In recent years, several biomaterials have been applied as barriers or deterrents to prevent the compression of neural structures by postsurgical fibrosis. Methods: In this study, a new bacterial cellulose (BC) anti-adhesion membrane, composed of exosomes from human umbilical cord mesenchymal stem cells, was developed. Its structure and morphology, water content, thickness, and mechanical properties of elasticity were analyzed and characterized. The degradation of the BC+exosomes (BC+Exos) membrane in vitro was evaluated, and its in vitro cytotoxicity and in vivo biocompatibility were tested. The prevention effect of BC+Exos membrane on epidural fibrosis post-laminectomy in a rabbit model was investigated. Results: The BC+Exos membrane showed a three-dimensional network structure constituted of high-purity cellulose and moderate mechanical properties. No degeneration was observed. The BC+Exos membrane showed no cytotoxicity and displayed biocompatibility in vivo. The BC+Exos film was able to inhibit epidural fibrosis and peridural adhesions. Conclusion: Based on the current findings, the BC+Exos membrane is a promising material to prevent postoperative epidural fibrosis and adhesion. Keywords: failed back surgery syndrome, epidural fibrosis, adhesion, human umbilical cord mesenchymal stem cell, exosome, bacterial cellulose

Zhou D, Yang R, Yang T, Xing M, Luo G. Int J Nanomedicine. 2018;13:4157–4169. Page 4157, the Author affiliations are listed incorrectly, the correct list is shown below. Daijun Zhou1Ruijia Yang2Tao Yang1Malcolm Xing1,2Gaoxing Luo1 1Institute of Burn Research, State Key Laboratory of Trauma, Burn and Combined Injury, Key Laboratory of Proteomics of Chongqing, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, China; 2Department of Mechanical Engineering, University of Manitoba, Winnipeg, MB, Canada Read the original article.

Lianhua Zhu,1 Luofu Wang,2 Yu Liu,1 Dan Xu,1 Kejing Fang,1 Yanli Guo1 1Department of Ultrasound, Southwest Hospital, Third Military Medical University (Army Medical University), Shapingba District, Chongqing, China; 2Department of Urology, Daping Hospital, Third Military Medical University (Army Medical University), Yuzhong District, Chongqing, China Purpose: Targeted nanobubbles can penetrate the tumor vasculature and achieve ultrasound molecular imaging (USMI) of tumor parenchymal cells. However, most targeted nanobubbles only achieve USMI of tumor parenchymal cells from one organ, and their distribution, loading ability, and binding ability in tumors are not clear. Therefore, targeted nanobubbles loaded with carbonic anhydrase IX (CAIX) aptamer were fabricated for USMI of various tumors, and the morphological basis of USMI with targeted nanobubbles was investigated.Materials and methods: The specificity of CAIX aptamer at the cellular level was measured by immunofluorescence and flow cytometry. Targeted nanobubbles loaded with CAIX aptamer were prepared by a maleimide-thiol coupling reaction, and their binding ability to CAIX-positive tumor cells was analyzed in vitro. USMI of targeted and non-targeted nanobubbles was performed in tumor-bearing nude mice. The distribution, loading ability, and binding ability of targeted nanobubbles in xenograft tumor tissues were demonstrated by immunofluorescence.Results: CAIX aptamer could specifically bind to CAIX-positive 786-O and Hela cells, rather than CAIX-negative BxPC-3 cells. Targeted nanobubbles loaded with CAIX aptamer had the advantages of small size, uniform distribution, regular shape, and high safety, and they could specifically accumulate around 786-O and Hela cells, while not binding to BxPC-3 cells in vitro. Targeted nanobubbles had significantly higher peak intensity and larger area under the curve than non-targeted nanobubbles in 786-O and Hela xenograft tumor tissues, while there was no significant difference in the imaging effects of targeted and non-targeted nanobubbles in BxPC-3 xenograft tumor tissues. Immunofluorescence demonstrated targeted nanobubbles could still load CAIX aptamer after penetrating the tumor vasculature and specifically binding to CAIX-positive tumor cells in xenograft tumor tissues.Conclusion: Targeted nanobubbles loaded with CAIX aptamer have a good imaging effect in USMI of tumor parenchymal cells, and can improve the accuracy of early diagnosis of malignant tumors from various organs. Keywords: targeted ultrasound contrast agents, molecular imaging, malignant tumors, aptamers, morphological basis

Wenbin Cai,1,2,* Wei Lv,1,3,* Yang Feng,4 Hengli Yang,1 Yajun Zhang,1 Guodong Yang,5 Yunyou Duan,1 Jia Wang1 1Department of Ultrasound Diagnosis, Tang Du Hospital, Fourth Military Medical University, Xi'an 710038, China; 2General Hospital of Tibet Military Command, Lhasa, Tibet Autonomous Region, 850007, China; 3Department of Radiology, 305 Hospital of Chinese People's Liberation Army, Xicheng District, Beijing, 100017, China; 4Xijing Hospital, Traditional Chinese Medicine, Xi'an 710032, China; 5Department of Biochemistry and Molecular Biology, The Fourth Military Medical University, Xi'an 710032, China *These authors contributed equally to this work Background: Nanobubbles (NBs) combined with ultrasound-targeted destruction (UTD) have become promising potential carriers for drug or siRNA delivery. Due to their nano-size, NBs could penetrate tumor blood vessels and accumulate in intercellular spaces so that "sonoporation" induced by UTD would act directly on the tumor cells to increase cell membrane permeability. Methods: Based on the successful the fabrication of NBs, we synthesized NBs carrying siRNA (NBs-siRNA) by using a biotin-streptavidin system. We then utilized ultrasound irradiation (UI)-targeted NBs-siRNA to improve siRNA transfection and achieve the inhibition of glioma growth.Results: NBs as carriers combined with UI effectively enhanced siRNA transfection and the effect of silencing targeted genes in vitro. Additionally, a better therapeutic effect was shown in the NBs-siRNA with UI group in vivo compared with that of microbubbles (MBs) with UI or NBs-siRNA without UI.Conclusion: These results indicated that NBs combined with UTD might be an ideal delivery vector for siRNA to achieve the noninvasive treatment of glioma. Keywords: nanobubbles, ultrasound, siRNA, glioma

Dazhong Chen,1–3,* Xiaoli Pan,4,* Fangyuan Xie,5,* Ying Lu,2 Hao Zou,2 Chuan Yin,6 Yu Zhang,7 Jie Gao1,2 1Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325027, China; 2Department of Pharmaceutical Sciences, Second Military Medical University, Shanghai 200433, China; 3Department of Planning, Kunming General Hospital of Chengdu Military Command, Yunnan 650032, China; 4Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; 5Department of Pharmacy, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai 200438, China; 6Department of Gastroenterology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China; 7Department of Oncology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Hubei 441000, China *These authors contributed equally to this work Purpose: Liver cancer is the third leading cause of cancer-related deaths worldwide. Liver cancer stem cells (LCSCs) are a subpopulation of cancer cells that are responsible for the initiation, progression, drug resistance, recurrence, and metastasis of liver cancer. Recent studies have suggested that the eradication of both LCSCs and liver cancer cells is necessary because the conversion of cancer stem cells (CSCs) to cancer cells occasionally occurs. As ATP-binding cassette (ABC) transporters are overexpressed in both CSCs and cancer cells, combined therapies using ABC transporter inhibitors and chemotherapy drugs could show superior therapeutic efficacy in liver cancer. In this study, we developed poly(lactide-co-glycolide)/d-alpha-tocopherol polyethylene glycol 1000 succinate nanoparticles to accomplish the simultaneous delivery of an optimized ratio of doxorubicin (DOX) and elacridar (ELC) to target both LCSCs and liver cancer cells.Methods: Median-effect analysis was used for screening of DOX and ELC for synergy in liver cancer cells (HepG2 cells) and LCSCs (HepG2 tumor sphere [HepG2-TS]). Then, nanoparticles loaded with DOX and ELC at the optimized ratio (NDEs) were prepared by nanoprecipitation method. The cytotoxicity and colony and tumor sphere formation ability of nanoparticles were investigated in vitro, and the tissue distribution and antitumor activity of nanoparticles were evaluated in vivo.Results: We demonstrated that a DOX/ELC molar ratio of 1:1 was synergistic in HepG2 cells and HepG2-TS. NDEs were shown to exhibit significantly increased cytotoxic effects against both HepG2 and HepG2-TS compared with DOX-loaded nanoparticles (NDs) or ELC-loaded nanoparticles (NEs) in vitro. In vivo studies demonstrated that the nanoparticles exhibited better tumor targeting, with NDE showing the strongest antitumor activity with lower systemic toxicity.Conclusion: These results suggested that NDE represented a promising combination therapy against liver cancer by targeting both liver cancer cells and CSCs. Keywords: combined therapy, cancer stem cells, liver cancer, doxorubicin, elacridar, nanoparticles

Yue Lu,1 Wenjun Jiang,1 Xin Wu,2 Saixu Huang,1 Zhiyong Huang,1 Yamin Shi,3 Qi Dai,1 Jianming Chen,2 Fuzheng Ren,1 Shen Gao4 1Shanghai Key Lab New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, People's Republic of China; 2Shanghai Weier Biological Medicine Science and Technology Co. Ltd., Shanghai, People's Republic of China; 3Department of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, People's Republic of China; 4Department of Pharmaceutics, Changhai Hospital, Second Military Medical University, Shanghai, People's Republic of China Background: Vectors are essential for successful gene delivery. In the present study, a tumor-targeting cationic gene vector, known as the disulfide cross-linked arginine-aspartic acid peptide modified by HAIYPRH (T7) peptide (CRD-PEG-T7), was designed for targeted delivery of plasmid DNA (pDNA) for gene therapy of prostate cancer (PCa). Methods: The structure of CRD-PEG-T7 was determined and the cellular uptake efficacy, gene transfection efficacy, cytotoxicity, and the targeting effect of the CRD-PEG-T7–plasmid DNA complex were examined. Results: The results demonstrated that the CRD-PEG-T7–plasmid DNA complex was nanosized and had a positively charged surface, good cellular uptake efficacy, minimal cytotoxicity, and a dual-targeting effect as compared with the CRD-PEG–plasmid DNA complex. The peptide T7-modifed new delivery system was able to target the highly expressed transferrin receptor (TfR) on tumor cells with an efficiency four-fold higher than that of the non-modified system. Conclusion: The results above indicatd that the CRD-PEG-T7–plasmid DNA complex may prove to be a promising gene delivery system targeting bone-metastatic tumor. Keywords: arginine peptide, aspartic acid peptide, tumor targeting, DNA delivery, bone metastasis prostate cancer

Sergej Tomić,1,2 Nataša Ilić,1 Vanja Kokol,3 Alisa Gruden-Movsesijan,1 Dušan Mihajlović,2 Marina Bekić,1 Ljiljana Sofronić-Milosavljević,1 Miodrag ÄŒolić,1,2,4 Dragana VuÄević2 1Institute for the Application of Nuclear Energy, University of Belgrade, Belgrade, Serbia; 2Institute for Medical Research, Medical Faculty of the Military Medical Academy, University of Defense, Belgrade, Serbia; 3Institute of Engineering Materials and Design, University of Maribor, Maribor, Slovenia; 4Medical Faculty FoÄa, University of East Sarajevo, FoÄa, Bosnia and Herzegovina Background: Cellulose nanofibrils (CNF) are attractive nanomaterials for various biomedical applications due to their excellent biocompatibility and biomimetic properties. However, their immunoregulatory properties are insufficiently investigated, especially in relation to their functionalization, which could cause problems during their clinical application. Methods: Using a model of human dendritic cells (DC), which have a central role in the regulation of immune response, we investigated how differentially functionalized CNF, ie, native (n) CNF, 2,2,6,6-tetramethylpiperidine 1-oxyl radical-oxidized (c) CNF, and 3-aminopropylphosphoric acid-functionalized (APAc) CNF, affect DC properties, their viability, morphology, differentiation and maturation potential, and the capacity to regulate T cell-mediated immune response. Results: Nontoxic doses of APAcCNF displayed the strongest inhibitory effects on DC differentiation, maturation, and T helper (Th) 1 and Th17 polarization capacity, followed by cCNF and nCNF, respectively. These results correlated with a specific pattern of regulatory cytokines production by APAcCNF-DC and their increased capacity to induce suppressive CD8+CD25+IL-10+ regulatory T cells in immunoglobulin-like transcript (ILT)-3- and ILT-4-dependent manner. In contrast, nCNF-DC induced predominantly suppressive CD4+CD25hiFoxP3hi regulatory T cells in indolamine 2,3-dioxygenase-1-dependent manner. Different tolerogenic properties of CNF correlated with their size and APA functionalization, as well as with different expression of CD209 and actin bundles at the place of contact with CNF. Conclusion: The capacity to induce different types of DC-mediated tolerogenic immune responses by functionalized CNF opens new perspectives for their application as well-tolerated nanomaterials in tissue engineering and novel platforms for the therapy of inflammatory T cell-mediated pathologies. Keywords: cellulose nanofibrils, biocompatibility, tolerogenic dendritic cells, regulatory T-cell subsets, immunomodulation

Chan Wu,1,* Yang Zhang,1,2,* Daoqiu Yang,3,* Jinfeng Zhang,4 Juanjuan Ma,1 Dan Cheng,1 Jianming Chen,1,5 Li Deng1 1Department of Pharmaceutics, School of Pharmacy, Second Military Medical University, Shanghai 200433, People's Republic of China; 2Department of Pharmacy, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai 200072, People's Republic of China; 3Department of Dermatology, 107th Hospital of PLA, Yantai 264000, People's Republic of China; 4Department of Traditional Chinese Medicine, Shanghai Hospital of Chinese Integrative Medicine, Shanghai, People's Republic of China; 5Tasly Diyi Pharmaceutical Group Co., Ltd, Jiangsu 223002, People's Republic of China *These authors contributed equally to this work Background: Many novel drug delivery systems have been extensively studied to exploit the full therapeutic potential of SN38, which is one of the most potent antitumor analogs of camptothecins (CPTs), whose clinical application is seriously hindered by poor water solubility, low plasmatic stability, and severe toxicity, but results are always unsatisfactory.Methods: In this study, combining the advantages of prodrug and nanotechnology, a lipophilic prodrug of SN38, SN38-PA, was developed by conjugating palmitic acid to SN38 via ester bond at C10 position, and then the lipophilic prodrug was encapsulated into a long-circulating liposomal carrier by film dispersion method.Results: The SN38-PA liposomes were characterized as follows: an average particle size of 80.13 nm, an average zeta potential of -33.53 mv, and the entrapment efficiency of 99%. Compared with CPT-11, SN38-PA liposome was more stable in close lactone form, more efficient in conversion rate to SN38, and more potent in cytotoxicity against tumor cells. Pharmacokinetic study showed that SN38-PA liposome had significantly enhanced plasma half-life (t1/2) value of SN38 and increased area under the curve (AUC) of SN38, which was 7.5-fold higher than that of CPT-11. Biodistribution study showed that SN38-PA liposome had more active metabolite SN38 in each tissue. Finally, the pharmacodynamic study showed that SN38-PA liposome had higher antitumor effect with the antitumor inhibition rate of 1.61 times than that of CPT-11.Conclusion: These encouraging data merit further investigation on this novel SN38-PA liposome. Keywords: SN38, lipophilic prodrug, long-circulating liposome, pharmacokinetics, biodistribution, pharmacodynamics, CPT-11

This research proposes a buyer-supplier power-motivation interaction model that clarifies what multinational enterprises (MNEs) could do to encourage apparel suppliers' to implement code of conduct (CoCs) policies successfully in the apparel supply chain. Specifically, the aim of this study was to investigate how MNEs enforce CoC policies and how they affect suppliers' motivation to engage themselves in managing CoC compliance mechanisms of monitoring, enforcement and transparency, in the Indian apparel industry. A quantitative survey was conducted using face-to-face survey. Overall, 210 usable data was collected and analyzed by using structural equation modeling technique. Study findings highlighted that, of the two power strategies, only hard power was found applicable in the apparel Indian market. Nevertheless, among the different nature of hard power strategies, MNEs were found to use mainly authoritative/coercive strategies that induced only extrinsic motivation in suppliers. Due to this, suppliers were found to primarily engaged in CoC monitoring mechanisms, while not the transparency mechanisms. Based on these findings, it was concluded that inducing both intrinsic and extrinsic motivation in suppliers is important for buyers (MNEs) in order to develop a holistic CoC compliance mechanisms at suppliers' base. Overall, this study contributes uniquely to the literature by offering a deeper insight into the interactive nature of the buyer-supplier compliance-influencing process.

Academic field became one of the most increasingly growing industries in the world. If the growth rates of academic expenditures will be compared with countries' GDP growth rates, obviously there are essential difference between them. Education always was priority direction of government policy based on attaining high quality of population knowledge.

Anwar returned to the political fray for the country's youth despite the threat of imprisonment; they can rebuild the country with principles and tenacity of purpose

At the heart of new wars are economic structures, patterns of violence and formations of collective meaning, which appear to blend localised and globalised practices of gender. While new wars appear to mirror the kind of warrior masculinity that preceded the modern state, they also draw on new technologies and symbolism to give meaning to acts of war. In the case of foreign fighters, armed groups increasingly draw on globalised cultural products (film, electronic publications and images) to entice volunteers to fight on the battlefields of the 21st century. The use of masculine models and gendered discourses to recruit men to fight in these conflicts has been well studied. However, the process through which 'local' and 'global' practices of gender are blended by highly mobile fighters to forge the practices of new war has received far less attention. Drawing on the notion of cultural hybridity, this article asks how interactions between different configurations of gender make new wars possible. To do this, it empirically explores encounters between notions of militarised manhood through the lives of four Indonesian former foreign fighters. By utilising life history interviews, this article makes the case that the masculinity of these 'new warriors' relied on the tensions between, and synthesis of, anti-colonial notions of organised violence that are rooted in Indonesian history and globalised jihadi discourse on war.

Chengming Jia,1,2,* Hui Chen,3,* Mengying Wei,2,* Xiangjie Chen,4 Yajun Zhang,5 Liang Cao,1 Ping Yuan,1 Fangyuan Wang,1 Guodong Yang,2 Jing Ma1 1Department of Chinese Medicine, Xijing Hospital, The Fourth Military Medical University, Xi'an, China; 2Department of Biochemistry and Molecular Biology, The Fourth Military Medical University, Xi'an, China; 3Department of Plastic Surgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, China; 4Department of Mathematics, Southeast University, Nanjing, China; 5Department of Ultrasound Diagnosis, Tangdu Hospital, The Fourth Military Medical University, Xi'an, China *These authors contributed equally to this work Abstract: Diabetic cardiomyopathy is a common disease in postmenopausal women, in whom the estrogen deficiency aggravates the pathology. In this study, we have found that estrogen deficiency due to ovariectomy aggravates the inflammation in the hearts of diabetic mice, as depicted by excessive proinflammatory type 1 macrophages (M1) over anti-inflammatory type 2 macrophages (M2). Accordingly, an additional increase of reactive oxygen species, cell apoptosis, cardiac hypertrophy, and fibrosis was observed in the hearts of ovariectomized diabetic mice, in comparison with the diabetes-only group. Significantly, miR155, a potent promoter of M1 polarization, was found to be additionally enhanced in the macrophages and hearts by ovariectomy. Tail vein injection of miR155-AuNP, in which thiol-modified antago-miR155 was covalently conjugated with gold nanoparticle (AuNP), preferentially delivered the nucleic acids into the macrophages via phagocytosis. Together with the increased M2 ratio and reduced inflammation, in vivo delivery of antago-miR155 reduced cell apoptosis and restored the cardiac function. The restoration efficacy of miR155-AuNP was much better than general macrophage depletion by clodrosome. In summary, we revealed that M1/M2 imbalance contributes to the aggravated cardiomyopathy in ovariectomized diabetic mice, and therapeutically reducing miR155 in macrophages by AuNP serves as a promising strategy in improving cardiac function. Keywords: gold nanoparticle, miR155, cardiac function, macrophage, ovariectomized diabetic mouse model, targeted delivery

The purpose of this study is to explore and understand the European Union internal energy market processes and how European Union constructs and justifies the markets. The idea is to understand where and how the internal energy market is created and what underlying of socio-political features effects this economic program. Growing exploitation of renewable energy and electricity, especially solar and wind, sources have created an impact on the economic policies. This study contributes to the discussion in market and energy market studies. To further the analysis is done by analysing the EU's formal legislation, politics and policies provided in the high-ranking European Commission documents. The study aims to understand and elaborate on the EU's internal energy market policies and means (which can be regarded as economic) and how the EU avails these policies. Due to the centrality of the thought of sustainable development within the European region for decades, the European Union has been the forerunner in this development and the single energy market is in many ways a model example of this interdependency. Energy questions centralise these policies and the internal energy market combines them in one form. The key topics of this study are renewable energy, the integrated market, harmonising regulation, the growing influence amongst consumers and public intervention as well as unbundling and transparency. I take critical realist stance on economics. Critical realism is a thought where reality exists outside of the human representation of it, but at the same time, it does not view social as a closed system. In this sense, economic agents are not isolated. In this study, the themes of energy and economics are deeply related to the thematics of environmental politics and their development. The nexus of environmental issues has been transforming towards the concepts of climate, energy, economy and even security.