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Annals of the New York Academy of Sciences

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https://www.readbyqxmd.com/read/28505395/claudin-peptidomimetics-modulate-tissue-barriers-for-enhanced-drug-delivery
#1
Sophie Dithmer, Christian Staat, Carolin Müller, Min-Chi Ku, Andreas Pohlmann, Thoralf Niendorf, Nora Gehne, Petra Fallier-Becker, Ágnes Kittel, Fruzsina R Walter, Szilvia Veszelka, Maria A Deli, Rosel Blasig, Reiner F Haseloff, Ingolf E Blasig, Lars Winkler
The blood-brain barrier (BBB) formed by the microvascular endothelium limits cerebral drug delivery. The paraendothelial cleft is sealed by tight junctions (TJs) with a major contribution from claudin-5, which we selected as a target to modulate BBB permeability. For this purpose, drug-enhancer peptides were designed based on the first extracellular loop (ECL) of claudin-5 to allow transient BBB permeabilization. Peptidomimetics (C5C2 and derivatives, nanomolar affinity to claudin-5) size-selectively (≤40 kDa) and reversibly (12-48 h) increased the permeability of brain endothelial and claudin-5-transfected epithelial cell monolayers...
May 15, 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/28505392/beneficial-effects-of-ginger-zingiber-officinale-roscoe-on-obesity-and-metabolic-syndrome-a-review
#2
REVIEW
Jing Wang, Weixin Ke, Rui Bao, Xiaosong Hu, Fang Chen
In recent years, metabolic syndromes (MetSs), including diabetes mellitus, dyslipidemia, and cardiovascular diseases, have become a common health problem in both developed and developing countries. Accumulating data have suggested that traditional herbs might be able to provide a wide range of remedies in prevention and treatment of MetSs. Ginger (Zingiber officinale Roscoe, Zingiberaceae) has been documented to ameliorate hyperlipidemia, hyperglycemia, oxidative stress, and inflammation. These beneficial effects are mediated by transcription factors, such as peroxisome proliferator-activated receptors, adenosine monophosphate-activated protein kinase, and nuclear factor κB...
May 15, 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/28493289/intestinal-epithelial-claudins-expression-and-regulation-in-homeostasis-and-inflammation
#3
REVIEW
Vicky Garcia-Hernandez, Miguel Quiros, Asma Nusrat
The intestinal epithelium forms a highly dynamic and selective barrier that controls absorption of fluid and solutes while restricting pathogen access to underlying tissues. Barrier properties are achieved by intercellular junctions that include an apical tight junction (TJ) and subjacent adherens junctions and desmosomes. The TJ tetraspan claudin proteins form pores between epithelial cells to control paracellular fluid and ion movement. In addition to regulation of barrier function, claudin family members control epithelial homeostasis and are expressed in a spatiotemporal manner in the intestinal crypt-luminal axis...
May 10, 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/28493278/the-bicellular-tensile-force-sorts-the-localization-of-lsrs-in-bicellular-and-tricellular-junctions
#4
Takayuki Kohno, Shin Kikuchi, Takafumi Ninomiya, Takashi Kojima
Lipolysis-stimulated lipoprotein receptors (LSRs) localize to tricellular tight junctions. Recent studies have shown that changes in the localization and expression profiles of LSRs are associated with malignancy of endometrial carcinomas, although the precise mechanisms by which malignant progression induces changes in the localization of LSRs are still unknown. In this study, we found that changes in cell tension correlated with alterations in the junctional localization of LSRs in endometrial cancer Sawano cells...
May 10, 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/28464561/progress-toward-openness-transparency-and-reproducibility-in-cognitive-neuroscience
#5
REVIEW
Rick O Gilmore, Michele T Diaz, Brad A Wyble, Tal Yarkoni
Accumulating evidence suggests that many findings in psychological science and cognitive neuroscience may prove difficult to reproduce; statistical power in brain imaging studies is low and has not improved recently; software errors in analysis tools are common and can go undetected for many years; and, a few large-scale studies notwithstanding, open sharing of data, code, and materials remain the rare exception. At the same time, there is a renewed focus on reproducibility, transparency, and openness as essential core values in cognitive neuroscience...
May 2, 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/28445614/two-common-human-cldn5-alleles-encode-different-open-reading-frames-but-produce-one-protein-isoform
#6
Ronald M Cornely, Barbara Schlingmann, Whitney S Shepherd, Joshua D Chandler, David C Neujahr, Michael Koval
Claudins provide tight junction barrier selectivity. The human CLDN5 gene contains a high-frequency single-nucleotide polymorphism (rs885985), where the G allele codes for glutamine (Q) and the A allele codes for an amber stop codon. Thus, these different CLDN5 alleles define nested open reading frames (ORFs) encoding claudin-5 proteins that are 303 or 218 amino acids in length. Interestingly, human claudin-16 and claudin-23 also have long ORFs. The long form of claudin-5 contrasts with the majority of claudin-5 proteins in the National Center for Biotechnology Information protein database, which are less than 220 amino acids in length...
April 26, 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/28445611/equivalence-of-complex-drug-products-advances-in-and-challenges-for-current-regulatory-frameworks
#7
Leonie Hussaarts, Stefan Mühlebach, Vinod P Shah, Scott McNeil, Gerrit Borchard, Beat Flühmann, Vera Weinstein, Sesha Neervannan, Elwyn Griffiths, Wenlei Jiang, Elena Wolff-Holz, Daan J A Crommelin, Jon S B de Vlieger
Biotechnology and nanotechnology provide a growing number of innovator-driven complex drug products and their copy versions. Biologics exemplify one category of complex drugs, but there are also nonbiological complex drug products, including many nanomedicines, such as iron-carbohydrate complexes, drug-carrying liposomes or emulsions, and glatiramoids. In this white paper, which stems from a 1-day conference at the New York Academy of Sciences, we discuss regulatory frameworks in use worldwide (e.g., the U...
April 26, 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/28445594/porcine-milk-induces-a-strengthening-of-barrier-function-in-porcine-jejunal-epithelium-in-vitro
#8
Judith Radloff, Silke S Zakrzewski, Robert Pieper, Alexander G Markov, Salah Amasheh
Milk contains a variety of components that have been shown to affect the expression and localization of epithelial tight junction proteins and therefore the intestinal barrier. Thus, we hypothesized that milk would have an effect on intestinal barrier properties, owing to effects on the tight junction in an intraspecies porcine intestinal in vitro model. Jejunal samples of piglets derived from different age groups were analyzed. Transepithelial electrical resistance was recorded employing the Ussing chamber technique...
April 26, 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/28445589/a-network-engineering-perspective-on-probing-and-perturbing-cognition-with-neurofeedback
#9
REVIEW
Danielle S Bassett, Ankit N Khambhati
Network science and engineering provide a flexible and generalizable tool set to describe and manipulate complex systems characterized by heterogeneous interaction patterns among component parts. While classically applied to social systems, these tools have recently proven to be particularly useful in the study of the brain. In this review, we describe the nascent use of these tools to understand human cognition, and we discuss their utility in informing the meaningful and predictable perturbation of cognition in combination with the emerging capabilities of neurofeedback...
April 26, 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/28445585/c-type-starches-and-their-derivatives-structure-and-function
#10
REVIEW
Zebin Guo, Xiangze Jia, Beibei Zhao, Shaoxiao Zeng, Jianbo Xiao, Baodong Zheng
The C-type starches are widely distributed in seeds or rhizomes of various legumes, medicinal plants, and crops. These carbohydrate polymers directly affect the application of starchy plant resources. The structural and crystal properties of starches are crucial parameters of starch granules, which significantly influence their physicochemical and mechanical properties. The unique crystal structure consisting of both A- and B-type polymorphs endows C-type starches with specific crystal adjustability. Furthermore, large proportions of resistant starches and slowly digestible starches are C-type starches, which contribute to benign glycemic response and proliferation of gut microflora...
April 26, 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/28437576/irisin-and-musculoskeletal-health
#11
Graziana Colaianni, Saverio Cinti, Silvia Colucci, Maria Grano
Irisin is a hormone-like myokine produced in abundance by skeletal muscle in response to exercise, both in mice and humans. Once released into the circulation, irisin acts on white adipocytes to induce the browning response and subsequently activates nonshivering thermogenesis. We have examined the premise that irisin produced during exercise may subserve further functions in the musculoskeletal system. We review evidence for its possible skeletal effects, including the central role that irisin plays in the control of bone mass, with positive effects on cortical mineral density and geometry in mice...
April 24, 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/28436082/tricellulin-is-a-target-of-the-ubiquitin-ligase-itch
#12
Susanne Jennek, Sonnhild Mittag, Juliane Reiche, Julie K Westphal, Stefanie Seelk, Max J Dörfel, Thorsten Pfirrmann, Karlheinz Friedrich, Anja Schütz, Udo Heinemann, Otmar Huber
Tricellulin, a member of the tight junction-associated MAGUK protein family, preferentially localizes to tricellular junctions in confluent polarized epithelial cell layers and is downregulated during the epithelial-mesenchymal transition. Posttranslational modifications are assumed to play critical roles in the process of downregulation of tricellulin at the protein level. Here, we report that the E3 ubiquitin ligase Itch forms a complex with tricellulin and thereby enhances its ubiquitination. Pull-down assays confirmed a direct interaction between tricellulin and Itch, which is mediated by the Itch WW domain and the N-terminus of tricellulin...
April 24, 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/28436044/structure-bioactivity-and-synthesis-of-methylated-flavonoids
#13
REVIEW
Lingrong Wen, Yueming Jiang, Jiali Yang, Yupeng Zhao, Miaomiao Tian, Bao Yang
Methylated flavonoids are an important type of natural flavonoid derivative with potentially multiple health benefits; among other things, they have improved bioavailability compared with flavonoid precursors. Flavonoids have been documented to have broad bioactivities, such as anticancer, immunomodulation, and antioxidant activities, that can be elevated, to a certain extent, by methylation. Understanding the structure, bioactivity, and bioavailability of methylated flavonoids, therefore, is an interesting topic with broad potential applications...
April 24, 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/28423468/cytoprotective-effects-of-dietary-flavonoids-against-cadmium-induced-toxicity
#14
REVIEW
Xia Li, Xinwei Jiang, Jianxia Sun, Cuijuan Zhu, Xiaoling Li, Lingmin Tian, Liu Liu, Weibin Bai
Cadmium (Cd) damages the liver, kidney, bones, reproductive system, and other organs. Flavonoids, such as anthocyanins and flavonols, which are commonly found in plant foods, have shown protective effects against Cd-induced damage. The cytoprotective effects of flavonoids against Cd-induced diseases are mainly attributable to three mechanisms. First, flavonoids clear reactive oxygen species, thereby reducing lipid peroxide production and improving the activity of antioxidation enzymes. Second, flavonoids chelate Cd, thus reducing the accumulation of Cd and altering the levels of other essential metal ions in vivo...
April 19, 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/28423466/zonulin-transgenic-mice-show-altered-gut-permeability-and-increased-morbidity-mortality-in-the-dss-colitis-model
#15
Craig Sturgeon, Jinggang Lan, Alessio Fasano
Increased small intestinal permeability (IP) has been proposed to be an integral element, along with genetic makeup and environmental triggers, in the pathogenies of chronic inflammatory diseases (CIDs). We identified zonulin as a master regular of intercellular tight junctions linked to the development of several CIDs. We aim to study the role of zonulin-mediated IP in the pathogenesis of CIDs. Zonulin transgenic Hp2 mice (Ztm) were subjected to dextran sodium sulfate (DSS) treatment for 7 days, followed by 4-7 days' recovery and compared to C57Bl/6 (wild-type (WT)) mice...
April 19, 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/28415156/endocytosis-of-tight-junction-proteins-and-the-regulation-of-degradation-and-recycling
#16
REVIEW
Svetlana M Stamatovic, Allison M Johnson, Nikola Sladojevic, Richard F Keep, Anuska V Andjelkovic
Internalization of tight junction (TJ) proteins from the plasma membrane is a pivotal mechanism regulating TJ plasticity and function in both epithelial and endothelial barrier tissues. Once internalized, the TJ proteins enter complex vesicular machinery, where further trafficking is directly dependent on the initiating stimulus and downstream signaling pathways that regulate the sorting and destiny of TJ proteins, as well as on cell and barrier responses. The destiny of internalized TJ proteins is recycling to the plasma membrane or sorting to late endosomes and degradation...
April 17, 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/28415154/annona-species-annonaceae-a-rich-source-of-potential-antitumor-agents
#17
REVIEW
Rosa Tundis, Jianbo Xiao, Monica R Loizzo
Plants have provided the basis of traditional medicine systems throughout the world for thousands of years and continue to yield molecules for new remedies. We analyzed studies published from 2009 to 2016 on the Annona species (Annonaceae), including A. coriacea, A. crassifolia, A. hypoglauca, A. muricata, A. squamosa, A. sylvatica, and A. vepretorum, as sources of potential antitumor agents. Here, we report and discuss the mechanisms of action and structure-activity relationships of the most active Annona constituents...
April 17, 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/28415153/polar-and-charged-extracellular-residues-conserved-among-barrier-forming-claudins-contribute-to-tight-junction-strand-formation
#18
Anna Piontek, Jan Rossa, Jonas Protze, Hartwig Wolburg, Caroline Hempel, Dorothee Günzel, Gerd Krause, Jörg Piontek
Claudins (Cldn) form the backbone of tight junction (TJ) strands and thereby regulate paracellular permeability for solutes and water. Polymeric strands are formed by homo- and heterophilic cis- and trans-interactions between claudin protomers. Crystal structures of some claudins have been resolved; however, the mechanism by which claudins assemble into TJ strands remains unclear. To elucidate strand architecture, TJ-like strands were reconstituted in HEK293 cells by claudin transfection. Determinants of prototypic, classic barrier-forming claudins (Cldn1, -3, and -5) involved in strand formation were analyzed by mutagenesis...
April 17, 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/28415142/neural-correlates-of-cognitive-processing-in-monolinguals-and-bilinguals
#19
REVIEW
John G Grundy, John A E Anderson, Ellen Bialystok
Here, we review the neural correlates of cognitive control associated with bilingualism. We demonstrate that lifelong practice managing two languages orchestrates global changes to both the structure and function of the brain. Compared with monolinguals, bilinguals generally show greater gray matter volume, especially in perceptual/motor regions, greater white matter integrity, and greater functional connectivity between gray matter regions. These changes complement electroencephalography findings showing that bilinguals devote neural resources earlier than monolinguals...
April 17, 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/28415141/claudin-targeted-drug-development-using-anti-claudin-monoclonal-antibodies-to-treat-hepatitis-and-cancer
#20
REVIEW
Yosuke Hashimoto, Masayoshi Fukasawa, Hiroki Kuniyasu, Kiyohito Yagi, Masuo Kondoh
The 27-member family of tetraspan membrane proteins known as claudins (CLDNs) is a major component of tight junctions. A series of studies elucidating the relationship between CLDNs and various pathological conditions has provided new insights into drug development. For instance, CLDN-1 may be a potent target for epidermal absorption of drugs and for treating hepatitis C virus (HCV) infection. CLDN-4 may be a target for treating cancer. Because CLDNs are also expressed in various normal tissues, safety and efficacy evaluations are critical for translational research...
April 17, 2017: Annals of the New York Academy of Sciences
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