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Muhammad Naeem, Junhwan Bae, Murtada A Oshi, Min-Soo Kim, Hyung Ryong Moon, Bok Luel Lee, Eunok Im, Yunjin Jung, Jin-Wook Yoo
Background: Colon-targeted oral nanoparticles (NPs) have emerged as an ideal, safe, and effective therapy for ulcerative colitis (UC) owing to their ability to selectively accumulate in inflamed colonic mucosa. Cyclosporine A (CSA), an immunosuppressive agent, has long been used as rescue therapy in severe steroid-refractory UC. In this study, we developed CSA-loaded dual-functional polymeric NPs composed of Eudragit® FS30D as a pH-sensitive polymer for targeted delivery to the inflamed colon, and poly(lactic-co-glycolic acid) (PLGA) as a sustained-release polymer...
2018: International Journal of Nanomedicine
Lianzi He, Yuanyuan Deng, Jianmei Gao, Lingrong Zeng, Qihai Gong
BACKGROUND: Excitotoxicity is extensively recognized as a major pathological process of neuronal death and has been proved to play a key role in Alzheimer's disease (AD). ICS II, a flavonoid compound from Herba Epimedii Maxim, is attracting great interests due to its neuroprotective properties. PURPOSE: The present study was aimed to explore the effects of ICS II on cognitive dysfunction and apoptotic response induced by excitatory neurotoxin ibotenic acid (IBO) injection in rats...
March 1, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
Yang Yang, Wei-Gang Ji, Zhi-Ru Zhu, Yu-Ling Wu, Zhi-Yang Zhang, Shao-Chen Qu
Rhynchophylline (RIN) is a significant active component isolated from the Chinese herbal medicine Uncaria rhynchophylla. The overproduction of soluble amyloid β protein (Aβ) oligomers in the hippocampus is closely involved in impairments in cognitive function at the early stage of Alzheimer's disease (AD). Growing evidences show that RIN possesses neuroprotective effects against Aβ-induced neurotoxicity. However, whether RIN can prevent soluble Aβ1-42 -induced impairments in spatial cognitive function and synaptic plasticity is still unclear...
March 3, 2018: Neuropharmacology
Xu Chu, Shuhu Zhou, Ran Sun, Lin Wang, Chunye Xing, Ruqing Liang, Qingxia Kong
Patients with diabetes mellitus are easy to experience diabetic encephalopathy (DE) and other cognition dysfunction, whereas the neural alterations in developing this disease are unknown yet. Chrysophanol (CHR) is one of traditional Chinese medicine which was reported to show protective effects in cognition dysfunction and inflammatory in previously studies. In this current study, whether CHR protects learning and memory dysfunctions induced by diabetes disease or not and underlying mechanisms were studied...
March 1, 2018: Neurochemical Research
Marta Portero-Tresserra, Margarita Martí-Nicolovius, Mireia Tarrés-Gatius, Ana Candalija, Gemma Guillazo-Blanch, Anna Vale-Martínez
RATIONALE: Aging is characterized by a decrease in N-methyl-D-aspartate receptors (NMDARs) in the hippocampus, which might be one of the factors involved in the age-dependent cognitive decline. D-Cycloserine (DCS), a partial agonist of the NMDAR glycine recognition site, could improve memory deficits associated to neurodegenerative disorders and cognitive deficits observed in normal aging. OBJECTIVES AND METHODS: The aim of the present study was to explore whether DCS would reverse age-dependent memory deficits and decreases in NMDA receptor subunits (GluN1, GluN2A, and GluN2B) and the presynaptic protein synaptophysin in Wistar rats...
February 28, 2018: Psychopharmacology
Manish Kumar, Nitin Bansal
The present study was undertaken to elucidate the role of PI3-kinase signaling in memory enhancing potential of caffeic acid phenethyl ester (CAPE) against cognitive defects in rats after centrally administered streptozotocin as a model of Alzheimer's disease. The Morris water maze and elevated plus maze paradigms showed profound loss of memory in adult Wistar rats (180-200 g) injected with streptozotocin (3 mg/kg) bilaterally (STZ-ICV) on day 1 and 3. Intraperitoneal administration of CAPE (6 mg/kg, i...
February 24, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Wei Zhang, Yi Guo, Bo Li, Qi Zhang, Jian-Hui Liu, Guo-Jun Gu, Jin-Hong Wang, Rui-Kang Bao, Yu-Jie Chen, Jian-Rong Xu
Cerebral amyloid angiopathy (CAA) is present in up to 90% of patients with Alzheimer's disease (AD), and may interact with classical neuropathology to exacerbate cognitive decline. Since growth differentiation factor 11 (GDF11) can activate vascular remodeling, we tested its effects on cognitive function and neuroinflammatory changes of AD model mice. We intravenously administered GDF11 or vehicle daily to 12-month-old transgenic mice overexpressing the amyloid-β protein precursor (AβPP)/PS1). Cognitive function was monitored using the Morris water maze, and after conclusion of the treatment, we assessed the morphology and presence of inflammatory markers in the cerebral vasculature...
2018: Journal of Alzheimer's Disease: JAD
Monika Oláhová, Wan Hee Yoon, Kyle Thompson, Sharayu Jangam, Liliana Fernandez, Jean M Davidson, Jennifer E Kyle, Megan E Grove, Dianna G Fisk, Jennefer N Kohler, Matthew Holmes, Annika M Dries, Yong Huang, Chunli Zhao, Kévin Contrepois, Zachary Zappala, Laure Frésard, Daryl Waggott, Erika M Zink, Young-Mo Kim, Heino M Heyman, Kelly G Stratton, Bobbie-Jo M Webb-Robertson, Michael Snyder, Jason D Merker, Stephen B Montgomery, Paul G Fisher, René G Feichtinger, Johannes A Mayr, Julie Hall, Ines A Barbosa, Michael A Simpson, Charu Deshpande, Katrina M Waters, David M Koeller, Thomas O Metz, Andrew A Morris, Susan Schelley, Tina Cowan, Marisa W Friederich, Robert McFarland, Johan L K Van Hove, Gregory M Enns, Shinya Yamamoto, Euan A Ashley, Michael F Wangler, Robert W Taylor, Hugo J Bellen, Jonathan A Bernstein, Matthew T Wheeler
ATP synthase, H+ transporting, mitochondrial F1 complex, δ subunit (ATP5F1D; formerly ATP5D) is a subunit of mitochondrial ATP synthase and plays an important role in coupling proton translocation and ATP production. Here, we describe two individuals, each with homozygous missense variants in ATP5F1D, who presented with episodic lethargy, metabolic acidosis, 3-methylglutaconic aciduria, and hyperammonemia. Subject 1, homozygous for c.245C>T (p.Pro82Leu), presented with recurrent metabolic decompensation starting in the neonatal period, and subject 2, homozygous for c...
February 16, 2018: American Journal of Human Genetics
Haibin Wu, Zezhou Liu, Anand Jagota, Chung-Yuen Hui
A line force acting on a soft elastic solid, say due to the surface tension of a liquid drop, can cause significant deformation and the formation of a kink close to the point of force application. Analysis based on linearized elasticity theory shows that sufficiently close to its point of application, the force is borne entirely by the surface stress, not by the elasticity of the substrate; this local balance of three forces is called Neumann's triangle. However, it is not difficult to imagine realistic properties for which this force balance cannot be satisfied...
February 19, 2018: Soft Matter
C W Ryan, K Bishop, D D Blaney, S J Britton, F Cantone, C Egan, M G Elrod, C W Frye, A M Maxted, G Perkins
Melioidosis in humans presents variably as fulminant sepsis, pneumonia, skin infection and solid organ abscesses. It is caused by Burkholderia pseudomallei, which in the United States is classified as a select agent, with "potential to pose a severe threat to both human and animal health, to plant health or to animal and plant products" (Federal Select Agent Program,, accessed 22 September 2016). Burkholderia pseudomallei is found in soil and surface water in the tropics, especially South-East Asia and northern Australia, where melioidosis is endemic...
February 16, 2018: Zoonoses and Public Health
Marc Blancher, François Albasini, Fidel Elsensohn, Ken Zafren, Natalie Hölzl, Kyle McLaughlin, Albert R Wheeler, Steven Roy, Hermann Brugger, Mike Greene, Peter Paal
Blancher, Marc, François Albasini, Fidel Elsensohn, Ken Zafren, Natalie Hölzl, Kyle McLaughlin, Albert R. Wheeler III, Steven Roy, Hermann Brugger, Mike Greene, and Peter Paal. Management of multi-casualty incidents in mountain rescue. High Alt Med Biol. 00:000-000, 2018. INTRODUCTION: Multi-Casualty Incidents (MCI) occur in mountain areas. Little is known about the incidence and character of such events, and the kind of rescue response. Therefore, the International Commission for Mountain Emergency Medicine (ICAR MEDCOM) set out to provide recommendations for the management of MCI in mountain areas...
February 15, 2018: High Altitude Medicine & Biology
Hiroki Inahashi, Israt Jahan Shelley, Takaki Yamauchi, Shunsaku Nishiuchi, Misuzu Takahashi-Nosaka, Maya Matsunami, Atsushi Ogawa, Yusaku Noda, Yoshiaki Inukai
Auxin flow is important for different root developmental processes such as root formation, emergence, elongation and gravitropism. However, the detailed information about the mechanisms regulating the auxin flow is less well understood in rice. We characterized the auxin transport-related mutants, Ospin-formed2-1 (Ospin2-1) and Ospin2-2, which exhibited curly root phenotypes and altered lateral root-formation patterns in rice. The OsPIN2 gene encodes a member of the auxin-efflux carrier proteins that possibly regulates the basipetal auxin flow from the root tip towards the root-elongation zone...
February 15, 2018: Physiologia Plantarum
Alexander Young, Valentin Kochenkov, Jenifer K McIntyre, John D Stark, Allison B Coffin
After a storm, water often runs off of impervious urban surfaces directly into aquatic ecosystems. This stormwater runoff is a cocktail of toxicants that have serious effects on the ecological integrity of aquatic habitats. Zebrafish that develop in stormwater runoff suffer from cardiovascular toxicity and impaired growth, but the effects of stormwater on fish sensory systems are not understood. Our study investigated the effect of stormwater on hair cells of the lateral line in larval zebrafish and coho salmon...
February 12, 2018: Scientific Reports
Fernanda Neumann, Stéphanie Gourdain, Christelle Albac, Alain D Dekker, Linh Chi Bui, Julien Dairou, Isabelle Schmitz-Afonso, Nathalie Hue, Fernando Rodrigues-Lima, Jean M Delabar, Marie-Claude Potier, Jean-Pierre Le Caër, David Touboul, Benoît Delatour, Kevin Cariou, Robert H Dodd
Inhibition of DYRK1A kinase, produced by chromosome 21 and consequently overproduced in trisomy 21 subjects, has been suggested as a therapeutic approach to treating the cognitive deficiencies observed in Down syndrome (DS). We now report the synthesis and potent DYRK1A inhibitory activities of fluoro derivatives of 3,5-di(polyhydroxyaryl)-7-azaindoles (F-DANDYs). One of these compounds (3-(4-fluorophenyl)-5-(3,4-dihydroxyphenyl)-1H-pyrrolo[2,3-b]pyridine, 5a) was selected for in vivo studies of cognitive rescuing effects in a standard mouse model of DS (Ts65Dn line)...
February 12, 2018: Scientific Reports
Sarah Delmas, Robert Porteous, Dave H Bergin, Allan E Herbison
The roles of kisspeptin signaling outside the hypothalamus in the brain are unknown. We examined here the impact of Kiss1r-deletion on hippocampus-related behaviors of anxiety and spatial learning in adult male mice using two mouse models. In the first, global Kiss1r-null and control mice were gonadectomized (GDX KISS1R-KO). In the second, KISS1R signalling was rescued selectively in gonadotropin-releasing hormone neurons to generate Kiss1r-null mice with normal testosterone levels (intact KISS1R-KO). Intact KISS1R-KO rescue mice were found to spend twice as much time in the open arms of the elevated plus maze (EPM) compared to controls (P < 0...
February 12, 2018: Scientific Reports
Sarah M Clark, Chloe N Vaughn, Jennifer A Soroka, Xin Li, Leonardo H Tonelli
Accumulating evidence has shown that lymphocytes modulate behavior and cognition by direct interactions with the central nervous system. Studies have shown that reconstitution by adoptive transfer of lymphocytes from wild type into immune deficient mice restores a number of neurobehavioral deficits observed in these models. Moreover, it has been shown that these effects are mostly mediated by T lymphocytes. Studies of adoptive transfer thus far have employed adult mice, but whether lymphocytes may also modulate behavior during development remains unknown...
February 11, 2018: European Journal of Neuroscience
Valerie T Y Tan, Bruce G Mockett, Shane M Ohline, Karen D Parfitt, Hollie E Wicky, Katie Peppercorn, Lucia Schoderboeck, Mohamad Fairuz Bin Yahaya, Warren P Tate, Stephanie M Hughes, Wickliffe C Abraham
Alzheimer's disease (AD) is a neurodegenerative disease driven in large part by accumulated deposits in the brain of the amyloid precursor protein (APP) cleavage product amyloid-β peptide (Aβ). However, AD is also characterised by reductions in secreted amyloid precursor protein-alpha (sAPPα), an alternative cleavage product of APP. In contrast to the neurotoxicity of accumulated Αβ, sAPPα has many neuroprotective and neurotrophic properties. Increasing sAPPα levels has the potential to serve as a therapeutic treatment that mitigates the effects of Aβ and rescue cognitive function...
February 9, 2018: Molecular Brain
Giacomo Strapazzon, Oliver Reisten, Fabien Argenone, Ken Zafren, Greg Zen-Ruffinen, Gordon L Larsen, Inigo Soteras
Canyoning is a recreational activity that has increased in popularity in the last decade in Europe and North America, resulting in up to 40% of the total search and rescue costs in some geographic locations. The International Commission for Mountain Emergency Medicine convened an expert panel to develop recommendations for on-site management and transport of patients in canyoning incidents. The goal of the current review is to provide guidance to healthcare providers and canyoning rescue professionals about best practices for rescue and medical treatment through the evaluation of the existing best evidence, focusing on the unique combination of remoteness, water exposure, limited on-site patient management options, and technically challenging terrain...
February 5, 2018: Wilderness & Environmental Medicine
Matthew Hayes, Vineet Choudhary, Namrata Ojha, John Jh Shin, Gil-Soo Han, George M Carman, Christopher Jr Loewen, William A Prinz, Timothy Levine
Fat storage-inducing transmembrane (FIT or FITM) proteins have been implicated in the partitioning of triacylglycerol to lipid droplets and the budding of lipid droplets from the ER. At the molecular level, the sole relevant interaction is that FITMs directly bind to triacyglycerol and diacylglycerol, but how they function at the molecular level is not known. Saccharomyces cerevisiae has two FITM homologues: Scs3p and Yft2p. Scs3p was initially identified because deletion leads to inositol auxotrophy, with an unusual sensitivity to addition of choline...
December 28, 2017: Microbial Cell
Stacey Willcox-Pidgeon, Bridget Kool, Kevin Moran
In many countries, beaches are a high-risk location for drowning. In New Zealand, youth and young adults are particularly at risk of drowning at beaches, accounting for 17.4% of drowning deaths and 18.4% of rescues at surf beaches between 2008 and 2013, over 90% of fatalities were male. This study explored New Zealand youth risk perceptions of drowning and their coping appraisal processes at a surf beach. A cross-sectional survey of high school students (n = 599) was conducted between February and April 2014...
February 8, 2018: International Journal of Injury Control and Safety Promotion
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