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Shear AND apoptosis

Qianming Lin, Yumeng Yang, Qian Hu, Zhong Guo, Tao Liu, Jiake Xu, Jianping Wu, Thomas Brett Kirk, Dong Ma, Wei Xue
: Hydrogels have attracted much attention in cancer therapy and tissue engineering due to their sustained gene delivery ability. To obtain an injectable and high-efficiency gene delivery hydrogel, methoxypolyethylene glycol (MPEG) was used to conjugate with the arginine-functionalized poly(L-lysine) dendron (PLLD-Arg) by click reaction, and then the synthesized MPEG-PLLD-Arg interacted with α-cyclodextrin (α-CD) to form the supramolecular hydrogel by the host-guest interaction. The gelation dynamics, hydrogel strength and shear viscosity could be modulated by α-CD content in the hydrogel...
November 30, 2016: Acta Biomaterialia
Mikko S Venäläinen, Mika E Mononen, Jari Salo, Lasse P Räsänen, Jukka S Jurvelin, Juha Töyräs, Tuomas Virén, Rami K Korhonen
Focal cartilage lesions can proceed to severe osteoarthritis or remain unaltered even for years. A method to identify high risk defects would be of utmost importance to guide clinical decision making and to identify the patients that are at the highest risk for the onset and progression of osteoarthritis. Based on cone beam computed tomography arthrography, we present a novel computational model for evaluating changes in local mechanical responses around cartilage defects. Our model, based on data obtained from a human knee in vivo, demonstrated that the most substantial alterations around the defect, as compared to the intact tissue, were observed in minimum principal (compressive) strains and shear strains...
November 29, 2016: Scientific Reports
Jovana Serbanovic-Canic, Amalia de Luca, Christina Warboys, Pedro F Ferreira, Le A Luong, Sarah Hsiao, Ismael Gauci, Marwa Mahmoud, Shuang Feng, Celine Souilhol, Neil Bowden, John-Paul Ashton, Henning Walczak, David Firmin, Rob Krams, Justin C Mason, Dorian O Haskard, Spencer Sherwin, Victoria Ridger, Timothy J A Chico, Paul C Evans
OBJECTIVE: Atherosclerosis is initiated at branches and bends of arteries exposed to disturbed blood flow that generates low shear stress. This mechanical environment promotes lesions by inducing endothelial cell (EC) apoptosis and dysfunction via mechanisms that are incompletely understood. Although transcriptome-based studies have identified multiple shear-responsive genes, most of them have an unknown function. To address this, we investigated whether zebrafish embryos can be used for functional screening of mechanosensitive genes that regulate EC apoptosis in mammalian arteries...
November 10, 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
Jianhui Yao, Jingxian Feng, Xiaoling Gao, Dan Wei, Ting Kang, Qianqian Zhu, Tianze Jiang, Xunbin Wei, Jun Chen
Antiangiogenesis therapy has been served as a potent cancer treatment strategy for decades, yet disrupting neovasculature would provoke tumor cells into invasive growth and result in distal metastasis. The basic cause of cancer metastasis can be traced down to the presence of circulating tumor cells (CTCs) which detach from primary tumor site and act as 'seeds'. Epithelial cell adhesion molecule (EpCAM) is a potential biomarker for selective capture of epithelium-derived CTCs. Here, we integrated tumor neovessles-targetable ligands K237 peptide with Ep23 aptamer against EpCAM into a single drug-loaded nanoplatform using paclitaxel (PTX) as the model drug, aiming at damaging the primary tumor and neutralizing CTCs simultaneously to achieve a synergistic anti-tumor therapeutic effect...
October 22, 2016: Biomaterials
Xinlei Song, Shu Zhang, Yanna Cheng, Ting Zhao, Qianqian Lian, Lu Lu, Fengshan Wang
OBJECTIVES: To evaluate the resuscitative efficacy and the effect on reperfusion injury of two site-specific PEGylated human serum albumins modified with linear or branched PEG20kDa, compared with saline, 8% human serum albumin and 25% human serum albumin, in a hemorrhagic shock model. SETTING: Laboratory. SUBJECTS: Male Wistar rats. DESIGN: Prospective study. INTERVENTIONS: Rats were bled to hemorrhagic hypovolemic shock and resuscitated with different resuscitation fluids...
November 2016: Critical Care Medicine
Ching-Yan C Yeung, David F Holmes, Helen A Thomason, Christian Stephenson, Brian Derby, Matthew J Hardman
Pressure ulcers are complex wounds caused by pressure- and shear-induced trauma to skin and underlying tissues. Pressure-reducing devices, such as dressings, have been shown to successfully reduce pressure ulcer incidence, when used in adjunct to pressure ulcer preventative care. While pressure-reducing devices are available in a range of materials, with differing mechanical properties, understanding of how a material's mechanical properties will influence clinical efficacy remains limited. The aim of this study was to establish a standardised ex vivo model to allow comparison of the cell protection potential of two gel-like pressure-reducing devices with differing mechanical properties (elastic moduli of 77 kPa v 35 kPa)...
September 26, 2016: Wound Repair and Regeneration
C J McDonnell, C D Garciarena, R L Watkin, T M McHale, A McLoughlin, J Claes, P Verhamme, P M Cummins, S W Kerrigan
BACKGROUND: Vascular endothelial dysfunction with associated oedema and organ failure is one of the hallmarks of sepsis. While a large number of microorganisms can cause sepsis, Staphylococcus aureus is one of the primary etiological agents. Currently there are no approved specific treatments for sepsis and therefore the initial management bundle focuses on cardiorespiratory resuscitation and mitigation against the immediate threat of uncontrolled infection. The continuous emergence of antibiotic resistant strains of bacteria urges the development of new therapeutic approaches for this disease...
September 8, 2016: Journal of Thrombosis and Haemostasis: JTH
Justin C Mason
The vascular endothelium is a critical interface, which separates the organs from the blood and its contents. The endothelium has a wide variety of functions and maintenance of endothelial homeostasis is a multi-dimensional active process, disruption of which has potentially deleterious consequences if not reversed. Vascular injury predisposes to endothelial apoptosis, dysfunction and development of atherosclerosis. Endothelial dysfunction is an end-point, a central feature of which is increased ROS generation, a reduction in endothelial nitric oxide synthase and increased nitric oxide consumption...
August 9, 2016: Vascular Pharmacology
Lin Zhao, Chongxi Fan, Yu Zhang, Yang Yang, Dongjin Wang, Chao Deng, Wei Hu, Zhiqiang Ma, Shuai Jiang, Shouyi Di, Zhigang Qin, Jianjun Lv, Yang Sun, Wei Yi
Adiponectin has been demonstrated to protect the cardiovascular system and bone marrow mesenchymal stem cells (BMSCs). However, it is unclear whether adiponectin can protect BMSCs against flow shear stress (FSS). In this study, our aim was to explore the effects of adiponectin on BMSCs and to explore the role of AMP-activated protein kinase (AMPK) signaling in this process. Shear stress significantly inhibits the survival and increases the apoptosis of BMSCs in an intensity-dependent manner. The expression levels of TGF-β, bFGF, VEGF, PDGF, and Bcl2 are simultaneously reduced, and the phosphorylation levels of AMPK and ACC, as well as the expression level of Bax, are increased...
2016: Scientific Reports
Afu Fu, Shijun Ma, Na Wei, Blanche Xiao Xuan Tan, Ern Yu Tan, Kathy Qian Luo
Understanding the survival mechanism of metastatic cancer cells in circulation will provide new perspectives on metastasis prevention and also shed new light on metastasis-derived drug resistance. In this study, we made it feasible to detect apoptosis of circulating tumor cells (CTCs) in real-time by integrating a fluorescence resonance energy transfer (FRET)-based caspase sensor into one in vitro microfluidic circulatory system, and two in vivo models: zebrafish circulation and mouse lung metastatic model...
July 1, 2016: Oncotarget
Niravkumar R Patel, Aleksandr Piroyan, Abbegial H Nack, Corin A Galati, Mackenzi McHugh, Samantha Orosz, Amanda W Keeler, Sara O'Neal, William C Zamboni, Barbara Davis, Timothy P Coleman
Platinum (Pt) based chemotherapy is widely used to treat many types of cancer. Pt therapy faces challenges such as dose limiting toxicities, cumulative side effects, and multidrug resistance. Nanoemulsions (NEs) have tremendous potential in overcoming these challenges as they can be designed to improve circulation time, limit non-disease tissue uptake, and enhance tumor uptake by surface modification. We designed novel synthesis of three difattyacid platins, dimyrisplatin, dipalmiplatin, and distearyplatin, suitable for encapsulation in the oil core of an NE...
May 24, 2016: Molecular Pharmaceutics
Varun Chawla, Agneta Simionescu, Eugene M Langan, Martine LaBerge
BACKGROUND: In this study, we subjected vascular smooth muscle cells (VSMC) to acute and chronic high glucose conditions under physiologically relevant levels of cyclic strain and low wall shear forces to compare phenotypic modulation and thus conceptualize a dynamic-disease test model which captures cellular response more accurately in comparison with static cultures. METHODS: P2-P6 rat aortic smooth muscle cells were seeded on type I collagen-coated silicone membranes and subjected to 0-7% cyclic strain at 1 Hz and 0...
July 2016: Annals of Vascular Surgery
Geng Bin, Zhang Bo, Wang Jing, Jiang Jin, Tan Xiaoyi, Chen Cong, An Liping, Ma Jinglin, Wang Cuifang, Chen Yonggang, Xia Yayi
TNF-α is known to induce osteoblasts apoptosis, whereas mechanical stimulation has been shown to enhance osteoblast survival. In the present study, we found that mechanical stimulation in the form of fluid shear stress (FSS) suppresses TNF-α induced apoptosis in MC3T3-E1 cells. Extracellular signal-regulated kinase 5 (ERK5) is a member of the mitogen-activated protein kinase (MAPK) family that has been implicated in cell survival. We also demonstrated that FSS imposed by flow chamber in vitro leads to a markedly activation of ERK5, which was shown to be protective against TNF-α-induced apoptosis, whereas the transfection of siRNA against ERK5 (ERK5-siRNA) reversed the FSS-medicated anti-apoptotic effects...
May 1, 2016: Experimental Cell Research
Grzegorz Szczęsny, Aniela Brodzikowska, Ryszard Galus, Paweł Włodarski, Krzysztof H Włodarski
New data concerning the function of osteocytes as the central regulators of bone homeostasis are briefly outlined. It is established that osteocytes are the main target cells for parathormone. They are a rich source of sclerostin, the main inhibitor of osteoblast activity, and of the RANKL cytokine, the most important regulator of osteoclastogenesis. Under shear stress causing microinjury, osteocytes enter programmed cell death (apoptosis) and osteocyte apoptosis is a signal for nearby healthy osteocytes to activate osteoclasts to resorb bone...
November 2015: Ortopedia, Traumatologia, Rehabilitacja
Ceyda Tuba Sengel-Turk, Canan Hascicek, Filiz Bakar, Elif Simsek
Recent clinical and epidemiological researches have declared that non-steroidal anti-inflammatory agents may display as antineoplastic agents and indicate pro-apoptotic and antiproliferative effects on cancer cells. The major purpose of this research was to develop a novel poly(ethyleneglycol)-block-poly(ε-caprolactone) (PEG-b-PCL) nano-sized particles encapsulated with nimesulide (NMS), a selective COX-2 inhibitor, and to evaluate its anticancer activity against MCF-7 breast cancer cells. NMS-encapsulated PEG-b-PCL nanoparticles were fabricated using three different production techniques: (i) by emulsion-solvent evaporation using a high shear homogenizer, (ii) by emulsion-solvent evaporation using an ultrasonicator, and (iii) by nanoprecipitation...
March 23, 2016: AAPS PharmSciTech
Zhaohuan Li, Lin Wang, Xiaobo Hu, Pengfei Zhang, Yifei Chen, Xinxin Liu, Mingjun Xu, Yun Zhang, Mei Zhang
OBJECTIVES: The present study aimed to investigate the effect of potent rosuvastatin therapy on plaque mechanical stabilization as seen on IVUSE. METHODS: 14 purebred New Zealand rabbits were fed a high-cholesterol diet; the abdominal aorta endothelium was balloon-injured after 2 weeks; at week 13, 7 rabbits received rosuvastatin (1.5 mg/kg/day), and the other 7 received an equal volume of saline. IVUS images of abdominal aortas were acquired, and 2 consecutive frames near the end-diastole images in situ were used to construct an IVUS elastogram...
May 2016: Atherosclerosis
N M Attupuram, A Kumaresan, K Narayanan, H Kumar
Retention of fetal membranes (RFM), where the fetal placenta is not expelled within 8-12 hr after calving, lowers bovine productivity and fertility, resulting in significant economic loss to the dairy industry. Several risk factors that predispose an individual to RFM are known, but a unifying pathogenesis remains elusive due to its multifactorial etiology. Fetal membrane separation and expulsion after parturition involves structural and immunological changes of the bovine placentome that are governed predominantly by steroid hormones and the prostaglandin milieu of late pregnancy and parturition...
April 2016: Molecular Reproduction and Development
Ya-Ju Chang, Hui-Chun Huang, Yuan-Yu Hsueh, Shao-Wei Wang, Fong-Chin Su, Chih-Han Chang, Ming-Jer Tang, Yi-Shuan Li, Shyh-Hau Wang, Kirk K Shung, Shu Chien, Chia-Ching Wu
Little is known regarding the interplays between the mechanical and molecular bases for vein graft restenosis. We elucidated the stenosis initiation using a high-frequency ultrasonic (HFU) echogenicity platform and estimated the endothelium yield stress from von-Mises stress computation to predict the damage locations in living rats over time. The venous-arterial transition induced the molecular cascades for autophagy and apoptosis in venous endothelial cells (ECs) to cause neointimal hyperplasia, which correlated with the high echogenicity in HFU images and the large mechanical stress that exceeded the yield strength...
2016: Scientific Reports
Stephanie A Luff, Eleftherios T Papoutsakis
Megakaryocytes (MKs) are exposed to shear flow as they migrate from the bone marrow hematopoietic compartment into circulation to release pro/preplatelets into circulating blood. Shear forces promote DNA synthesis, polyploidization, and maturation in MKs, and platelet biogenesis. To investigate mechanisms underlying these MK responses to shear, we carried out transcriptional analysis on immature and mature stem cell-derived MKs exposed to physiological shear. In immature (day (d)9) MKs, shear exposure up-regulated genes related to growth and MK maturation, whereas in mature (d12) MKs, it up-regulated genes involved in apoptosis and intracellular transport...
April 8, 2016: Journal of Biological Chemistry
Robert Szulcek, Chris M Happé, Nina Rol, Ruud D Fontijn, Chris Dickhoff, Koen J Hartemink, Katrien Grünberg, Ly Tu, Wim Timens, George D Nossent, Marinus A Paul, Thomas A Leyen, Anton J Horrevoets, Frances S de Man, Christophe Guignabert, Paul B Yu, Anton Vonk-Noordegraaf, Geerten P van Nieuw Amerongen, Harm J Bogaard
RATIONALE: Altered pulmonary hemodynamics and fluid flow-induced high shear stress (HSS) are characteristic hallmarks in the pathogenesis of pulmonary arterial hypertension (PAH). However, the contribution of HSS to cellular and vascular alterations in PAH is unclear. OBJECTIVES: We hypothesize that failing shear adaptation is an essential part of the endothelial dysfunction in all forms of PAH and tested whether microvascular endothelial cells (MVECs) or pulmonary arterial endothelial cells (PAECs) from lungs of patients with PAH adapt to HSS and if the shear defect partakes in vascular remodeling in vivo...
June 15, 2016: American Journal of Respiratory and Critical Care Medicine
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