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https://www.readbyqxmd.com/read/28632993/the-role-of-small-gtpases-and-epac-rap-signaling-in-the-regulation-of-the-blood-brain-and-blood-retinal-barriers
#1
Carla J Ramos, David A Antonetti
Maintenance and regulation of the vascular endothelial cell junctional complex is critical for proper barrier function of the blood-brain barrier (BBB) and the highly related blood-retinal barrier (BRB) that help maintain proper neuronal environment. Recent research has demonstrated that the junctional complex is actively maintained and can be dynamically regulated. Studies focusing on the mechanisms of barrier formation, maintenance, and barrier disruption have been of interest to understanding development of the BBB and BRB and identifying a means for therapeutic intervention for diseases ranging from brain tumors and dementia to blinding eye diseases...
June 9, 2017: Tissue Barriers
https://www.readbyqxmd.com/read/28615944/the-interactions-of-single-wall-carbon-nanohorns-with-polar-epithelium
#2
Yujie Shi, Zujin Shi, Suxin Li, Yuan Zhang, Bing He, Dong Peng, Jie Tian, Ming Zhao, Xueqing Wang, Qiang Zhang
Single-wall carbon nanohorns (SWCNHs), which have multitudes of horn interstices, an extensive surface area, and a spherical aggregate structure, offer many advantages over other carbon nanomaterials being used as a drug nanovector. The previous studies on the interaction between SWCNHs and cells have mostly emphasized on cellular uptake and intracellular trafficking, but seldom on epithelial cells. Polar epithelium as a typical biological barrier constitutes the prime obstacle for the transport of therapeutic agents to target site...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28606376/enhanced-delivery-and-effects-of-acid-sphingomyelinase-by-icam-1-targeted-nanocarriers-in-type-b-niemann-pick-disease-mice
#3
Carmen Garnacho, Rajwinder Dhami, Melani Solomon, Edward H Schuchman, Silvia Muro
Acid sphingomyelinase deficiency in type B Niemann-Pick disease leads to lysosomal sphingomyelin storage, principally affecting lungs, liver, and spleen. Infused recombinant enzyme is beneficial, yet its delivery to the lungs is limited and requires higher dosing than liver and spleen, leading to potentially adverse reactions. Previous studies showed increased enzyme pulmonary uptake by nanocarriers targeted to ICAM-1, a protein overexpressed during inflammation. Here, using polystyrene and poly(lactic-co-glycolic acid) nanocarriers, we optimized lung delivery by varying enzyme dose and nanocarrier concentration, verified endocytosis and lysosomal trafficking in vivo, and evaluated delivered activity and effects...
June 9, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28601906/unravelling-the-regulation-of-insulin-transport-across-the-brain-endothelial-cell
#4
Sarah M Gray, Kevin W Aylor, Eugene J Barrett
AIMS/HYPOTHESIS: For circulating insulin to act on the brain it must cross the blood-brain barrier (BBB). Remarkably little is known about how circulating insulin crosses the BBB's highly restrictive brain endothelial cells (BECs). Therefore, we examined potential mechanisms regulating BEC insulin uptake, signalling and degradation during BEC transcytosis, and how transport is affected by a high-fat diet (HFD) and by astrocyte activity. METHODS: (125)I-TyrA14-insulin uptake and transcytosis, and the effects of insulin receptor (IR) blockade, inhibition of insulin signalling, astrocyte stimulation and an HFD were tested using purified isolated BECs (iBECs) in monoculture and co-cultured with astrocytes...
June 11, 2017: Diabetologia
https://www.readbyqxmd.com/read/28587148/the-role-of-caveolin-1-in-hiv-infection-and-pathogenesis
#5
REVIEW
Ayalew Mergia
Caveolin 1 (Cav-1) is a major component of the caveolae structure and is expressed in a variety of cell types including macrophages, which are susceptible to human immunodeficiency virus (HIV) infection. Caveolae structures are present in abundance in mechanically stressed cells such as endothelial cells and adipocytes. HIV infection induces dysfunction of these cells and promotes pathogenesis. Cav-1 and the caveolae structure are believed to be involved in multiple cellular processes that include signal transduction, lipid regulation, endocytosis, transcytosis, and mechanoprotection...
May 26, 2017: Viruses
https://www.readbyqxmd.com/read/28585535/blood-brain-barrier-spheroids-as-an-in-vitro-screening-platform-for-brain-penetrating-agents
#6
Choi-Fong Cho, Justin M Wolfe, Colin M Fadzen, David Calligaris, Kalvis Hornburg, E Antonio Chiocca, Nathalie Y R Agar, Bradley L Pentelute, Sean E Lawler
Culture-based blood-brain barrier (BBB) models are crucial tools to enable rapid screening of brain-penetrating drugs. However, reproducibility of in vitro barrier properties and permeability remain as major challenges. Here, we report that self-assembling multicellular BBB spheroids display reproducible BBB features and functions. The spheroid core is comprised mainly of astrocytes, while brain endothelial cells and pericytes encase the surface, acting as a barrier that regulates transport of molecules. The spheroid surface exhibits high expression of tight junction proteins, VEGF-dependent permeability, efflux pump activity and receptor-mediated transcytosis of angiopep-2...
June 6, 2017: Nature Communications
https://www.readbyqxmd.com/read/28559042/self-assembled-core-shell-type-lipid-polymer-hybrid-nanoparticles-intracellular-trafficking-and-relevance-for-oral-absorption
#7
Qiuxia Li, Dengning Xia, Jinsong Tao, Aijun Shen, Yuan He, Yong Gan, Chi Wang
Lipid-polymer hybrid nanoparticles (NPs) are advantageous for drug delivery. However, their intracellular trafficking mechanism and relevance for oral drug absorption are poorly understood. In this study, self-assembled core-shell lipid-polymer hybrid NPs made of PLGA and various lipids were developed to study their differing intracellular trafficking in intestinal epithelial cells, and their relevance for oral absorption of a model drug saquinavir (SQV). Our results demonstrated that the endocytosis and exocytosis of hybrid NPs could be changed by varying the kind of lipid...
May 27, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28557433/ligand-mediated-and-enzyme-directed-precise-targeting-and-retention-for-the-enhanced-treatment-of-glioblastoma
#8
Shaobo Ruan, Wei Xiao, Chuan Hu, Huajin Zhang, Jingdong Rao, Sihan Wang, Xiao Wang, Qin He, Huile Gao
Glioblastoma (GBM), one of the most lethal cancers, remains as a hard task to handle. The major hurdle of nanostructured therapeutic agents comes from the limited retention at the GBM site and poor selectivity. In this study, we reported dual-functional gold nanoparticles (AuNPs) to figure out the biological barrier and improve their accumulation in GBM. The nanoparticles, AuNP-A&C-R, were composed of two functional particles: one was Ala-Ala-Asn-Cys-Asp (AK) and R8-RGD-comodified AuNPs (AuNP-AK-R) and the other was 2-cyano-6-amino-benzothiazole and R8-RGD-comodified AuNPs (AuNP-CABT-R)...
June 21, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28549949/recent-advancements-in-liposomes-targeting-strategies-to-cross-blood-brain-barrier-bbb-for-the-treatment-of-alzheimer-s-disease
#9
REVIEW
Mukta Agrawal, Ajazuddin, Dulal K Tripathi, Swarnlata Saraf, Shailendra Saraf, Sophia G Antimisiaris, Spyridon Mourtas, Margareta Hammarlund-Udenaes, Amit Alexander
In this modern era, with the help of various advanced technologies, medical science has overcome most of the health-related issues successfully. Though, some diseases still remain unresolved due to various physiological barriers. One such condition is Alzheimer; a neurodegenerative disorder characterized by progressive memory impairment, behavioral abnormalities, mood swing and disturbed routine activities of the person suffering from. It is well known to all that the brain is entirely covered by a protective layer commonly known as blood brain barrier (BBB) which is responsible to maintain the homeostasis of brain by restricting the entry of toxic substances, drug molecules, various proteins and peptides, small hydrophilic molecules, large lipophilic substances and so many other peripheral components to protect the brain from any harmful stimuli...
May 24, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28541655/in-vitro-study-of-receptor-mediated-silica-nanoparticles-delivery-across-blood-brain-barrier
#10
Yang Song, Dan Du, Lei Li, Jun Xu, Prashanta Dutta, Yuehe Lin
A brain drug delivery system has been demonstrated by attaching lactoferrin (Lf) on the silica nanoparticles (Si NPs). The nanoparticle surface was modified with polyethylene glycol to reduce protein adsorption. The transport efficiency of Lf attached Si NPs was studied using an in vitro blood-brain barrier (BBB) model consisting of three distinct types of cells: endocytes, pericytes, and astrocytes. Transfer of NPs from the apical side to the basolateral side is observed. The results indicated that Lf attached Si NPs demonstrated enhanced transport efficiency across the BBB with size-dependence compared to bare Si NPs...
June 21, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28535336/transport-of-the-glucosamine-derived-browning-product-fructosazine-polyhydroxyalkylpyrazine-across-the-human-intestinal-caco-2-cell-monolayer-role-of-the-hexose-transporters
#11
Abhishek Bhattacherjee, Yuliya Hrynets, Mirko Betti
The transport mechanism of fructosazine, a glucosamine self-condensation product, was investigated using a Caco-2 cell model. Fructosazine transport was assessed by measuring the bidirectional permeability coefficient across Caco-2 cells. The mechanism of transport was evaluated using phlorizin, an inhibitor of sodium-dependent glucose cotransporters (SGLT) 1 and 2, phloretin and quercetin, inhibitors of glucose transporters (GLUT) 1 and 2, transcytosis inhibitor wortmannin, and gap junction disruptor cytochalasin D...
June 1, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28514851/blood-brain-barrier-penetrating-biologic-tnf-%C3%AE-inhibitor-for-alzheimer-s-disease
#12
Rudy Chang, Jillian Knox, Jae Chang, Aram Derbedrossian, Vitaly Vasilevko, David Cribbs, Ruben J Boado, William M Pardridge, Rachita Sumbria
OBJECTIVE: Tumor necrosis factor alpha (TNF-α) driven processes are involved at multiple stages of Alzheimer's disease (AD) pathophysiology and disease progression. Biologic TNF-α inhibitors (TNFIs) are the most potent class of TNFIs but cannot be developed for AD since these macromolecules do not cross the blood-brain barrier (BBB). A BBB-penetrating TNFI was engineered by the fusion of the extracellular domain of the type II human TNF receptor (TNFR) to a chimeric monoclonal antibody (MAb) against the mouse transferrin receptor (TfR), designated as the cTfRMAb-TNFR fusion protein...
May 17, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28501799/high-maternal-expression-of-siglec1-on-monocytes-as-a-surrogate-marker-of-a-type-i-interferon-signature-is-a-risk-factor-for-the-development-of-autoimmune-congenital-heart-block
#13
Anna R Lisney, Franziska Szelinski, Karin Reiter, Gerd R Burmester, Thomas Rose, Thomas Dörner
OBJECTIVES: Autoimmune congenital heart block (CHB) is associated with placental transcytosis of maternal autoantibodies directed against Ro/SS-A and La/SS-B. However, only about 2% of children born to mothers with the respective antibodies are affected, indicating that further risk factors exist, which are not yet fully understood. In this study, we investigated whether a maternal type I interferon (IFN) signature represents a risk factor for the development of CHB. METHODS: Blood samples, clinical data and serological parameters from 9 women with CHB pregnancies, 14 pregnant women with antibodies against Ro/SS-A but without a CHB complication and another 30 healthy pregnant women as controls were studied...
May 13, 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/28501469/routes-for-drug-translocation-across-the-blood-brain-barrier-exploiting-peptides-as-delivery-vectors
#14
REVIEW
Mie Kristensen, Birger Brodin
A number of potent drugs for the treatment of brain diseases are available. However, in order for them to reach their target site of action, they must pass the blood-brain barrier (BBB). The capillary endothelium comprises the major barrier of the BBB and allows only passive permeation of some small lipophilic molecules. Brain delivery of the larger biopharmaceuticals, which today includes an increasing number of novel drug entities, is therefore restricted; both due to their molecular size and their hydrophilic nature...
May 10, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28482500/non-invasive-approaches-for-drug-delivery-to-the-brain-based-on-the-receptor-mediated-transport
#15
REVIEW
Fei Fang, Dan Zou, Wei Wang, Ying Yin, Tieying Yin, Shilei Hao, Bochu Wang, Guixue Wang, Yazhou Wang
The blood brain barrier (BBB) is a physical and biochemical barrier that prevents entry of toxic compounds into brain for preserving homeostasis. However, the BBB also strictly limits influx of most therapeutic agents into the brain. One promising method for overcoming this problem to deliver drugs is receptor mediated transport (RMT) system, which employs the vesicular trafficking machinery to transport substrates across the BBB endothelium in a noninvasive manner. The conjugates of drug or drug-loaded vector linked with appropriate ligands specifically binds to the endogenous targeting receptor on the surface of the endothelial cells...
July 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/28440708/toward-in-vitro-to-in-vivo-translation-of-monoclonal-antibody-pharmacokinetics-application-of-a-neonatal-fc-receptor-mediated-transcytosis-assay-to-understand-the-interplaying-clearance-mechanisms
#16
Claudia A Castro Jaramillo, Sara Belli, Anne-Christine Cascais, Sherri Dudal, Martin R Edelmann, Markus Haak, Marie-Elise Brun, Michael B Otteneder, Mohammed Ullah, Christoph Funk, Franz Schuler, Silke Simon
Monoclonal antibodies (mAbs) are a rapidly growing drug class for which great efforts have been made to optimize certain molecular features to achieve the desired pharmacokinetic (PK) properties. One approach is to engineer the interactions of the mAb with the neonatal Fc receptor (FcRn) by introducing specific amino acid sequence mutations, and to assess their effect on the PK profile with in vivo studies. Indeed, FcRn protects mAbs from intracellular degradation, thereby prolongs antibody circulation time in plasma and modulates its systemic clearance...
April 25, 2017: MAbs
https://www.readbyqxmd.com/read/28435154/broadly-neutralizing-antibodies-suppress-post-transcytosis-hiv-1-infectivity
#17
V Lorin, M Malbec, C Eden, T Bruel, F Porrot, M S Seaman, O Schwartz, H Mouquet
No abstract text is available yet for this article.
May 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28431078/effect-of-threonine-on-secretory-immune-system-using-a-chicken-intestinal-ex%C3%A2-vivo-model-with-lipopolysaccharide-challenge
#18
Q Zhang, X Chen, S D Eicher, K M Ajuwon, T J Applegate
Secretory IgA (sIgA) and its transcytosis receptor, polymeric immunoglobulin receptor (pIgR), along with mucus, form the first lines of intestinal defense. Threonine (Thr) is a major component of intestinal mucins and IgA, which are highly secreted under lipopolysaccharide (LPS) induced inflammation. In the current study, the effect of Thr on the secretory immune system was determined in an ex vivo chicken ileal explant model. Results showed that a 2-hour Thr-deprivation of culture medium induced a compensatory increase in the mRNA expression of interleukin-8 (IL-8), mucin 2 ( ), and IgA during LPS challenge, and this increase was suppressed with Thr addition to the media ( P  ≤ 0...
April 18, 2017: Poultry Science
https://www.readbyqxmd.com/read/28424331/filtering-more-than-light-in-the-developing-retina
#19
Maria K Lehtinen
Restricting transcytosis is essential for blood-retinal barrier formation.
April 19, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28422786/antibody-mediated-immune-exclusion-of-hiv
#20
Ruth M Ruprecht, Samir K Lakhashe
PURPOSE OF REVIEW: Although approximately 90% of all HIV transmissions in humans occur through mucosal contact, the induction of mucosal anti-HIV immune responses has remained understudied. Here we summarize data demonstrating the powerful protection that is achievable at mucosal frontlines through virus-specific mucosal IgA alone or combined with IgG. RECENT FINDINGS: Passive immunization with different monoclonal antibody subclasses but identical epitope specificity (the conserved V3-loop crown of HIV gp120) has revealed that the dimeric IgA1 (dIgA1) form with its open hinge can prevent simian-human immunodeficiency virus (SHIV) acquisition in rhesus macaques at a higher rate than dIgA2...
May 2017: Current Opinion in HIV and AIDS
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