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https://www.readbyqxmd.com/read/30110616/intradiscal-delivery-of-celecoxib-loaded-microspheres-restores-intervertebral-disc-integrity-in-a-preclinical-canine-model
#1
A R Tellegen, I Rudnik-Jansen, M Beukers, A Miranda-Bedate, F C Bach, W de Jong, N Woike, G Mihov, J Thies, B P Meij, L B Creemers, M A Tryfonidou
Low back pain, related to degeneration of the intervertebral disc (IVD), affects millions of people worldwide. Clinical studies using oral cyclooxygenase-2 (COX-2) inhibitors have shown beneficial effects, although side-effects were reported. Therefore, intradiscal delivery of nonsteroidal anti-inflammatory drugs can be an alternative treatment strategy to halt degeneration and address IVD-related pain. In the present study, the controlled release and biologic potency of celecoxib, a selective COX-2 inhibitor, from polyesteramide microspheres was investigated in vitro...
August 12, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/30110558/trafficking-of-adhesion-and-growth-factor-receptors-and-their-effector-kinases
#2
Christina Schoenherr, Margaret C Frame, Adam Byron
Cell adhesion to macromolecules in the microenvironment is essential for the development and maintenance of tissues, and its dysregulation can lead to a range of disease states, including inflammation, fibrosis, and cancer. The biomechanical and biochemical mechanisms that mediate cell adhesion rely on signaling by a range of effector proteins, including kinases and associated scaffolding proteins. The intracellular trafficking of these must be tightly controlled in space and time to enable effective cell adhesion and microenvironmental sensing and to integrate cell adhesion with, and compartmentalize it from, other cellular processes, such as gene transcription, protein degradation, and cell division...
August 15, 2018: Annual Review of Cell and Developmental Biology
https://www.readbyqxmd.com/read/30109051/appetitive-information-seeking-behaviour-reveals-robust-daily-rhythmicity-for-internet-based-food-related-keyword-searches
#3
Nicolas Scrutton Alvarado, Tyler J Stevenson
There has been an exponential growth of information seeking behaviour (ISB) via Internet-based programs over the past decade. The availability of software that record ISB temporal patterns has provided a valuable opportunity to examine biological rhythms in human behaviour. Internet search repositories, such as Google Trends, permit the analyses of large datasets that can be used to track ISB on a domestic and international scale. We examined daily and seasonal Google Trends search patterns for keywords related to food intake, using the most relevant search terms for the USA, UK, Canada, India and Australia...
July 2018: Royal Society Open Science
https://www.readbyqxmd.com/read/30107211/muscle-fibrosis-in-the-soft-palate-delivery-of-cells-growth-factors-and-anti-fibrotics
#4
REVIEW
Johannes W Von den Hoff, Paola L Carvajal Monroy, Edwin M Ongkosuwito, Toin H van Kuppevelt, Willeke F Daamen
The healing of skeletal muscle injuries after major trauma or surgical reconstruction is often complicated by the development of fibrosis leading to impaired function. Research in the field of muscle regeneration is mainly focused on the restoration of muscle mass while far less attention is paid to the prevention of fibrosis. In this review, we take as an example the reconstruction of the muscles in the soft palate of cleft palate patients. After surgical closure of the soft palate, muscle function during speech is often impaired by a shortage of muscle tissue as well as the development of fibrosis...
August 11, 2018: Advanced Drug Delivery Reviews
https://www.readbyqxmd.com/read/30105447/cell-specific-gene-therapy-driven-by-an-optimized-hypoxia-regulated-vector-reduces-choroidal-neovascularization
#5
Manas R Biswal, Howard M Prentice, George W Smith, Ping Zhu, Yao Tong, C Kathleen Dorey, Alfred S Lewin, Janet C Blanks
Aberrant growth of blood vessels in the choroid layer of the eye, termed choroidal neovascularization (CNV), is the pathological hallmark of exudative age-related macular degeneration (AMD), causing irreversible blindness among the elderly. Co-localization of proangiogenic factors and hypoxia inducible factors (HIF) in neovascular membranes from AMD eyes suggests the role of hypoxia in pathogenesis of CNV. In order to utilize hypoxic conditions in RPE for therapeutic purposes, we developed an optimized hypoxia regulated, RPE cell-specific gene therapy to inhibit choroidal neovascularization...
August 13, 2018: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/30104744/the-complex-aetiology-of-cerebral-palsy
#6
REVIEW
Steven J Korzeniewski, Jaime Slaughter, Madeleine Lenski, Peterson Haak, Nigel Paneth
Cerebral palsy (CP) is the most prevalent, severe and costly motor disability of childhood. Consequently, CP is a public health priority for prevention, but its aetiology has proved complex. In this Review, we summarize the evidence for a decline in the birth prevalence of CP in some high-income nations, describe the epidemiological evidence for risk factors, such as preterm delivery and fetal growth restriction, genetics, pregnancy infection and other exposures, and discuss the success achieved so far in prevention through the use of magnesium sulfate in preterm labour and therapeutic hypothermia for birth-asphyxiated infants...
August 13, 2018: Nature Reviews. Neurology
https://www.readbyqxmd.com/read/30104317/predicting-intrapartum-fetal-compromise-at-term-using-the-cerebroplacental-ratio-and-placental-growth-factor-levels-promise-study-randomised-controlled-trial-protocol
#7
Helen Sherrell, Vicky Clifton, Sailesh Kumar
INTRODUCTION: Intrapartum complications are a major contributor to adverse perinatal outcomes, including stillbirth, hypoxic-ischaemic brain injury and subsequent longer term disability. In many cases, hypoxia develops as a gradual process due to the inability of the fetus to tolerate the stress of parturition suggesting reduced fetoplacental reserve before labour commences. The fetal cerebroplacental ratio (CPR) is an independent predictor of intrapartum fetal compromise, poor acid base status at birth and of neonatal unit admission at term...
August 13, 2018: BMJ Open
https://www.readbyqxmd.com/read/30102266/live-cell-imaging-of-the-tgf-%C3%AE-smad3-signaling-pathway-in-vitro-and-in-vivo-using-an-adenovirus-reporter-system
#8
Hao Chen, Thomas M B Ware, Josephine Iaria, Hong-Jian Zhu
Transforming Growth Factor β (TGF-β) signaling regulates many important functions required for cellular homeostasis and is commonly found overexpressed in many diseases, including cancer. TGF-β is strongly implicated in metastasis during late stage cancer progression, activating a subset of migratory and invasive tumor cells. Current methods for signaling pathway analysis focus on endpoint models, which often attempt to measure signaling post-hoc of the biological event and do not reflect the progressive nature of the disease...
July 30, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/30100766/polyethylene-glycol-in-spinal-cord-injury-repair-a-critical-review
#9
REVIEW
Xi Lu, T Hiran Perera, Alexander B Aria, Laura A Smith Callahan
Polyethylene glycol (PEG) is a synthetic biocompatible polymer with many useful properties for developing therapeutics to treat spinal cord injury. Direct application of PEG as a fusogen to the injury site can repair cell membranes, mitigate oxidative stress, and promote axonal regeneration to restore motor function. PEG can be covalently or noncovalently conjugated to proteins, peptides, and nanoparticles to limit their clearance by the reticuloendothelial system, reduce their immunogenicity, and facilitate crossing the blood-brain barrier...
2018: Journal of Experimental Pharmacology
https://www.readbyqxmd.com/read/30097441/vesicular-delivery-of-the-antifungal-antibiotics-of-lysobacter-enzymogenes-c3
#10
Paul R Meers, Carol Liu, Rensa Chen, William Bartos, Julianne Davis, Nicole Dziedzic, Jason Orciuolo, Szymon Kutyla, Maria Jose Pozo, Deepti Mithrananda, Dominick Panzera, Shu Wang
Lysobacter enzymogenes C3 is a predatory strain of gram-negative gliding bacteria that produces antifungal antibiotics by the polyketide synthetic pathway. Outer membrane vesicles (OMV) are formed as a stress response and can deliver virulence factors to host cells. The production of OMV by C3 and their role in antifungal activity are reported here. Vesicles in the range of 130-150 nm in diameter were discovered in the cell-free supernatants of C3 cultures. These OMV contain molecules characteristic of bacterial outer membranes, such as lipopolysaccharide and phospholipids...
August 10, 2018: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/30096765/scaffolds-as-structural-tools-for-bone-targeted-drug-delivery
#11
REVIEW
Riccardo Ferracini, Isabel Martínez Herreros, Antonio Russo, Tommaso Casalini, Filippo Rossi, Giuseppe Perale
Although bone has a high potential to regenerate itself after damage and injury, the efficacious repair of large bone defects resulting from resection, trauma or non-union fractures still requires the implantation of bone grafts. Materials science, in conjunction with biotechnology, can satisfy these needs by developing artificial bones, synthetic substitutes and organ implants. In particular, recent advances in materials science have provided several innovations, underlying the increasing importance of biomaterials in this field...
August 8, 2018: Pharmaceutics
https://www.readbyqxmd.com/read/30095054/targeted-drug-delivery-via-human-epidermal-growth-factor-receptor-for-sustained-release-of-allyl-isothiocyanate
#12
David Encinas-Basurto, Josue Juarez, Miguel A Valdez, Maria G Burboa, Silvia Barbosa, Pablo Taboada
In this study, allyl-isothiocyanate (AITC)-loaded polylactic-co-glycolic acid (PLGA) nanoparticles (NPs) were prepared for targeting epithelial squamous carcinoma cells using a specific antibody targeting the epidermal growth factor (EGF) receptor overexpressed on the cell membranes. AITC-loaded PLGA NPs showed more effective anticancer properties compared with free AITC, and their cytotoxicity was even more pronounced when the anti-EGFR antibody was covalently attached to the NPs surface. This targeting ability was additionally tested by co-culturing cervical HeLa cells, with very few EGFR on the membranes, and epithelial squamous carcinoma A431 cells, which largely overexpressed EFGR, being observed the specific localization of the antibody-functionalized AITC-loaded PLGA NPs solely in the latter types of cells, whereas non-functionalized NPs were distributed randomly in both cell types in much lesser extents...
August 10, 2018: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/30095012/modified-pamam-vehicles-for-effective-trail-gene-delivery-to-colon-adenocarcinoma-in-vitro-and-in-vivo-evaluation
#13
Elham Pishavar, Armin Attaranzadeh, Mona Alibolandi, Mohammad Ramezani, Maryam Hashemi
TRAIL (tumour necrosis factor-related apoptosis-inducing ligand) gene therapy is considered as one of the promising approaches for cancer treatment. Polyamidoamine (PAMAM) is one of the most extensively applied polymeric vector in gene delivery. In the current study, PAMAM (G4 and G5) dendrimers were modified with alkyl-carboxylate chain, PEG and cholesteryl chloroformate in order to enhance transfection efficiency through overcoming extracellular and intracellular barriers while reducing PAMAM cytotoxicity...
August 10, 2018: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/30094059/bone-tissue-engineering-via-growth-factor-delivery-from-scaffolds-to-complex-matrices
#14
REVIEW
Tinke-Marie De Witte, Lidy E Fratila-Apachitei, Amir A Zadpoor, Nicholas A Peppas
In recent years, bone tissue engineering has emerged as a promising solution to the limitations of current gold standard treatment options for bone related-disorders such as bone grafts. Bone tissue engineering provides a scaffold design that mimics the extracellular matrix, providing an architecture that guides the natural bone regeneration process. During this period, a new generation of bone tissue engineering scaffolds has been designed and characterized that explores the incorporation of signaling molecules in order to enhance cell recruitment and ingress into the scaffold, as well as osteogenic differentiation and angiogenesis, each of which is crucial to successful bone regeneration...
August 2018: Regenerative Biomaterials
https://www.readbyqxmd.com/read/30092402/the-supercarbonate-apatite-microrna-complex-inhibits-dextran-sodium-sulfate-induced-colitis
#15
Tadafumi Fukata, Tsunekazu Mizushima, Junichi Nishimura, Daisuke Okuzaki, Xin Wu, Haruka Hirose, Yuhki Yokoyama, Yui Kubota, Kazuya Nagata, Naoto Tsujimura, Akira Inoue, Norikatsu Miyoshi, Naotsugu Haraguchi, Hidekazu Takahashi, Taishi Hata, Chu Matsuda, Hisako Kayama, Kiyoshi Takeda, Yuichiro Doki, Masaki Mori, Hirofumi Yamamoto
The incidence of inflammatory bowel disease (IBD) is increasing. Nucleic acid-based medicine has potential as a next-generation treatment, but it is rarely successful with IBD. The aim of this study was to establish a microRNA-based therapy in an IBD model. For this purpose, we used microRNA-29 (miR-29) and a supercarbonate apatite (sCA) nanoparticle as a drug delivery system. Injection of sCA-miR-29a-3p or sCA-miR-29b-3p into mouse tail veins markedly prevented and restored inflammation because of dextran sulfate sodium (DSS)-induced colitis...
August 6, 2018: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/30092220/cerebrospinal-fluid-from-alzheimer-patients-affects-cell-mediated-nerve-growth-factor-production-and-cell-survival-in-vitro
#16
Maria Eriksdotter, Manuel Navarro-Oviedo, Sumonto Mitra, Lars Wahlberg, Bengt Linderoth, Lars O Tjernberg, Homira Behbahani
Alzheimer's disease (AD) is characterized by early degeneration of cholinergic neurons and decreased levels of nerve growth factor (NGF). Thus, increasing the NGF levels by for instance encapsulated cell bio-delivery (ECB) is a potential treatment strategy. The results from our previous first-in-human studies on ECB of NGF to the basal forebrain cholinergic neurons were promising, but indicated some variability of long-term viability of the encapsulated cells and associated reduced NGF-release. Here we studied the effect of amyloid beta-peptides (Aβ), interleukin 1-beta (IL-1β), and CSF from AD, Lewy body dementia (LBD) or subjective cognitive impairment (SCI) patients on the NGF overproducing cell line NGC-0295...
August 6, 2018: Experimental Cell Research
https://www.readbyqxmd.com/read/30092004/differential-effects-of-angiotensin-ii-type-i-receptor-blockers-on-reducing-intraocular-pressure-and-tgf%C3%AE-signaling-in-the-mouse-retina
#17
Ralph J Hazlewood, Qingxia Chen, Frances K Clark, John Kuchtey, Rachel W Kuchtey
PURPOSE: Angiotensin II type 1 receptor blockers (ARBs) have been investigated for their neuroprotective and intraocular pressure (IOP) lowering effects in treating glaucoma, but the reports have been inconsistent possibly because different compounds and models have been used. Here we selected three ARBs for head-to-head comparisons of their effects on IOP and transforming growth factor β (TGFβ) signaling, which is believed to play an important role in glaucoma pathogenesis. METHODS: Three ARBs (losartan, irbesartan or telmisartan) or vehicle controls were administered via chow to C57BL/6J mice for up to 7 days...
2018: PloS One
https://www.readbyqxmd.com/read/30091466/bone-targeted-delivery-of-tgf-%C3%AE-type-1-receptor-inhibitor-rescues-uncoupled-bone-remodeling-in-camurati-engelmann-disease
#18
Yunhao Qin, Shibing Tang, Gehua Zhen, Qiang Ding, Sheng Ding, Xu Cao
Camurati-Engelmann disease (CED) is a genetic bone-modeling disorder mainly caused by mutations in the gene that encodes transforming growth factor-β1 (TGF-β1). Symptoms of CED include bone pain, fractures, and dysplasia. Currently, effective therapies for bone fracture and dysplasia in CED are urgently needed. We have demonstrated that TGF-β1 is a coupling factor for bone remodeling and is aberrantly activated in CED. Daily injection of TGF-β type 1 receptor inhibitor (TβR1I) attenuated CED symptoms, but this systemic administration caused serious side effects...
August 9, 2018: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/30084153/erythropoiesis-and-chronic-kidney-disease-related-anemia-from-physiology-to-new-therapeutic-advancements
#19
REVIEW
Valeria Cernaro, Giuseppe Coppolino, Luca Visconti, Laura Rivoli, Antonio Lacquaniti, Domenico Santoro, Antoine Buemi, Saverio Loddo, Michele Buemi
Erythropoiesis is triggered by hypoxia and is strictly regulated by hormones, growth factors, cytokines, and vitamins to ensure an adequate oxygen delivery to all body cells. Abnormalities in one or more of these factors may induce different kinds of anemia requiring different treatments. A key player in red blood cell production is erythropoietin. It is a glycoprotein hormone, mainly produced by the kidneys, that promotes erythroid progenitor cell survival and differentiation in the bone marrow and regulates iron metabolism...
August 6, 2018: Medicinal Research Reviews
https://www.readbyqxmd.com/read/30083259/nano-delivery-of-fraxinellone-remodels-tumor-microenvironment-and-facilitates-therapeutic-vaccination-in-desmoplastic-melanoma
#20
Lin Hou, Qi Liu, Limei Shen, Yun Liu, Xueqiong Zhang, Fengqian Chen, Leaf Huang
Rationale: Tumor-associated fibroblasts (TAFs) play a critical role in the suppressive immune tumor microenvironment (TME), compromising the efficacy of immunotherapy. To overcome this therapeutic hurdle, we developed a nanoemulsion (NE) formulation to deliver fraxinellone (Frax), an anti-fibrotic medicine, to TAFs, as an approach to reverse immunosuppressive TME of desmoplastic melanoma. Methods: Frax NE was prepared by an ultrasonic emulsification method. The tumor inhibition effect was evaluated by immunofluorescence staining, masson trichrome staining and western blot analysis...
2018: Theranostics
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