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https://www.readbyqxmd.com/read/28808134/vps9a-activates-the-rab5-gtpase-ara7-to-confer-distinct-pre-and-post-invasive-plant-innate-immunity
#1
Mads Eggert Nielsen, Gerd Jürgens, Hans Thordal-Christensen
Plant innate immunity can effectively prevent the proliferation of filamentous pathogens. Papilla formation at the site of attack is essential for pre-invasive immunity; in post-invasive immunity the encasement of pathogen structures inside host cells can hamper disease. Whereas papillae are highly dependent on transcytosis of premade material, little is known about encasement formation. Here we show that endosome-associated VPS9a, the conserved guanine-nucleotide exchange factor activating Rab5 GTPases, is required for both pre- and post-invasive immunity against a non-adapted powdery mildew fungus (Blumeria graminis f...
August 14, 2017: Plant Cell
https://www.readbyqxmd.com/read/28797970/the-interaction-of-clozapine-loaded-nanocapsules-with-the-hcmec-d3-cells-in-vitro-model-of-blood-brain-barrier
#2
Sylwia Łukasiewicz, Ewa Błasiak, Krzysztof Szczepanowicz, Krzysztof Guzik, Małgorzata Bzowska, Piotr Warszyński, Marta Dziedzicka-Wasylewska
Despite progress in the development of novel pharmacological compounds, their efficacy in the treatment of neuropathologies is not satisfactory. One strategy to achieve safe and efficient brain targeting therapy is to design nanocarriers capable of transporting antipsychotic drugs through the BBB (without affecting the normal functions of the barrier) in a defined part of the brain. Here we investigate the interaction of clozapine-loaded polymeric Nano capsules (CLO-NCs) with hCMEC/D3 (human cerebral microvascular endothelial cells, D3 clone) cells that constitutes an in vitro model of the blood brain barrier (BBB)...
July 25, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28782363/transport-study-of-egg-derived-antihypertensive-peptides-lkp-and-iqw-using-caco-2-and-ht29-co-culture-monolayers
#3
Qingbiao Xu, Hongbing Fan, Wenlin Yu, Hui Hong, Jianping Wu
The objective of this study was to investigate the mechanisms of the transport of antihypertensive tripeptides LKP (Leu-Lys-Pro) and IQW (Ile-Gln-Trp) derived from egg white using a co-culture system of Caco-2 and HT29 cell monolayers. The results revealed that LKP and IQW have no cytotoxicity to the cell viability after 2 h-incubation, and could be transported intact across co-culture monolayers (apparent permeability coefficient: (18.11 ± 1.57) × 10-8 and (13.21 ± 1.12) × 10-8 cm/s, respectively), and were resistant to peptidase secreted by enterocytes...
August 7, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28752457/alpha-1-antitrypsin-transcytosis-and-secretion
#4
Angelia D Lockett
Protective levels of Alpha-1 antitrypsin (A1AT) are achieved in the lung through the uptake of the pulmonary vasculature of hepatocyte-secreted A1AT. The anti-inflammatory, anti-apoptotic, and anti-protease properties of A1AT are critical toward maintaining the function of pulmonary endothelial and epithelial cells and for the structural integrity of the pulmonary interstitium. To perform these functions A1AT must cross the pulmonary-endothelial barrier. Using transwell inserts, we have demonstrated that the endocytosis of A1AT at the apical surface of endothelial cells, followed by the transcytosis and secretion at the basolateral surface, is a mechanism through which A1AT is transported into the lung epithelium and interstitium...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28747713/overcoming-blood-brain-barrier-with-a-dual-purpose-temozolomide-loaded-lactoferrin-nanoparticles-for-combating-glioma-serp-17-12433
#5
Sonali Kumari, Saad M Ahsan, Jerald M Kumar, Anand K Kondapi, Nalam M Rao
Targeted delivery of drugs to the brain is challenging due to the restricted permeability across the blood brain barrier (BBB). Gliomas are devastating cancers and their positive treatment outcome using Temozolomide (TMZ) is limited due to its short plasma half-life, systemic toxicity and limited access through the blood-brain barrier (BBB). Nanoparticles made of Lactoferrin (Lf) protein, have been shown to enhance the pharmacological properties of drugs. Here, we report the specific ability of Lf nanoparticles to cross BBB and target over-expressed Lf receptors on glioma for enhanced TMZ delivery...
July 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28724654/mfsd2a-major-facilitator-superfamily-domain-containing-2a-attenuates-intracerebral-hemorrhage-induced-blood-brain-barrier-disruption-by-inhibiting-vesicular-transcytosis
#6
Yuan-Rui Yang, Xiao-Yi Xiong, Juan Liu, Li-Rong Wu, Qi Zhong, Kai Zhou, Zhao-You Meng, Liang Liu, Fa-Xiang Wang, Qiu-Wen Gong, Mao-Fan Liao, Chun-Mei Duan, Jie Li, Mei-Hua Yang, Qin Zhang, Chang-Xiong Gong, Qing-Wu Yang
BACKGROUND: Blood-brain barrier (BBB) disruption aggravates brain injury induced by intracerebral hemorrhage (ICH); however, the mechanisms of BBB damage caused by ICH remain elusive. Mfsd2a (major facilitator superfamily domain containing 2a) has been known to play an essential role in BBB formation and function. In this study, we investigated the role and underlying mechanisms of Mfsd2a in BBB permeability regulation after ICH. METHODS AND RESULTS: Using ICH models, we found that Mfsd2a protein expression in perihematomal brain tissues was significantly decreased after ICH...
July 19, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28713781/the-metalloprotease-mpr1-engages-annexina2-to-promote-the-transcytosis-of-fungal-cells-across-the-blood-brain-barrier
#7
Sarisa Na Pombejra, Michelle Salemi, Brett S Phinney, Angie Gelli
Eukaryotic pathogens display multiple mechanisms for breaching the blood-brain barrier (BBB) and invading the central nervous system (CNS). Of the fungal spp., that cause disease in mammals, only some cross brain microvascular endothelial cells which constitute the BBB, and invade the brain. Cryptococcus neoformans, the leading cause of fungal meningoencephalitis, crosses the BBB directly by transcytosis or by co-opting monocytes. We previously determined that Mpr1, a secreted fungal metalloprotease, facilitates association of fungal cells to brain microvascular endothelial cells and we confirmed that the sole expression of CnMPR1 endowed S...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28699828/glioma-targeted-delivery-strategy-of-doxorubicin-loaded-liposomes-by-dual-ligand-modification
#8
Wei Han, Guangfu Yin, Ximing Pu, Xianchun Chen, Xiaoming Liao, Zhongbing Huang
The blood-brain barrier (BBB) is the protective parclose of brain safety, but it is also the main obstacle of the drug delivery to cerebral parenchyma, which hamper therapy for brain diseases. In this work, a glioma targeted drug delivery system was developed through loading doxorubicin into Angiopep-2 and TAT peptide dual-modified liposomes (DOX-TAT-Ang-LIP). Low-density lipoprotein receptor-related protein-1 (LRP1) was one receptor overexpressed on both BBB and glioma cytomembranes. Angiopep-2, a specific ligand of LRP1, exhibited high LRP1 binding efficiency...
July 12, 2017: Journal of Biomaterials Science. Polymer Edition
https://www.readbyqxmd.com/read/28685576/egfr-egfrviii-dual-targeting-peptide-mediated-drug-delivery-for-enhanced-glioma-therapy
#9
Jiani Mao, Danni Ran, Cao Xie, Qing Shen, Songli Wang, Weiyue Lu
Tumor-homing peptides have been widely used to mediate active targeted drug delivery. l-AE is a reported targeting peptide demonstrating high binding affinity to epidermal growth factor receptor (EGFR) and mutation variant III (EGFRvIII) overexpressed on neovasculature, vasculogenic mimicry, tumor cells, and tumor stem cells. To improve its proteolytic stability, a d-peptide ligand (termed d-AE, the enantiomer of l-AE) was developed. d-AE was confirmed to bind receptors EGFR and EGFRvIII with targeting capability comparable to l-AE...
July 17, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28668390/ser-261-phospho-regulation-is-involved-in-ps256-and-ps269-mediated-aquaporin-2-apical-translocation
#10
Naofumi Yui, Fumiaki Ando, Sei Sasaki, Shinichi Uchida
Vasopressin catalyzes aquaporin-2 phosphorylation at several serine sites in the C-terminal region. Compared with Ser-256 and Ser-269 phosphorylation, the role of Ser-261 phospho-regulation on vasopressin-regulated AQP2 apical translocation is largely unknown. In addition, recent discovery of transcytotic apical delivery of AQP2 made the concept of its intracellular trafficking even more complicated. In this study, we evaluated how intact phospho-AQP2 signals fit with the transcytosis trafficking model in Madin-Darby canine kidney cells...
August 26, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28661032/cotransporting-ion-is-a-trigger-for-cellular-endocytosis-of-transporter-targeting-nanoparticles-a-case-study-of-high-efficiency-slc22a5-octn2-mediated-carnitine-conjugated-nanoparticles-for-oral-delivery-of-therapeutic-drugs
#11
Longfa Kou, Qing Yao, Mengchi Sun, Chunnuan Wu, Jia Wang, Qiuhua Luo, Gang Wang, Yuqian Du, Qiang Fu, Jian Wang, Zhonggui He, Vadivel Ganapathy, Jin Sun
OCTN2 (SLC22A5) is a Na(+) -coupled absorption transporter for l-carnitine in small intestine. This study tests the potential of this transporter for oral delivery of therapeutic drugs encapsulated in l-carnitine-conjugated poly(lactic-co-glycolic acid) (PLGA) nanoparticles (LC-PLGA NPs) and discloses the molecular mechanism for cellular endocytosis of transporter-targeting nanoparticles. Conjugation of l-carnitine to a surface of PLGA-NPs enhances the cellular uptake and intestinal absorption of encapsulated drug...
June 29, 2017: Advanced Healthcare Materials
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
#12
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
#13
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
#14
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...
July 5, 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
#15
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...
August 2017: Diabetologia
https://www.readbyqxmd.com/read/28587148/the-role-of-caveolin-1-in-hiv-infection-and-pathogenesis
#16
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
#17
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
#18
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
#19
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
#20
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
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