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https://www.readbyqxmd.com/read/29458211/impact-of-formulation-excipients-on-the-thermal-mechanical-and-electrokinetic-properties-of-hydroxypropyl-methylcellulose-acetate-succinate-hpmcas
#1
Tanvi M Deshpande, Anisul Quadir, Sakae Obara, Stephen W Hoag
Hydroxypropyl methylcellulose acetate succinate (HPMCAS) has been widely used in amorphous solid dispersions and as an enteric coating polymer. Under aqueous coating conditions and at elevated coating temperatures, HPMCAS particles tend to aggregate and clog the spray-nozzle, hence interrupting the coating process. This research focused on how plasticizers and surfactants, excipients used for aqueous coating, affect the properties and stability of HPMCAS. This information would be useful in identifying suitable excipients for developing a stable HPMCAS aqueous enteric coating formulation...
February 16, 2018: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/29458205/developing-a-stable-aqueous-enteric-coating-formulation-with-hydroxypropyl-methylcellulose-acetate-succinate-hpmcas-mf-and-colloidal-silicon-dioxide-as-anti-tacking-agent
#2
Tanvi M Deshpande, Anisul Quadir, Sakae Obara, Ahmed Ibrahim, Stephen W Hoag
The purpose of this study was to use statistical design of experiments to develop a stable aqueous enteric coating formulation containing stabilizing excipients, such as polyethylene glycol that can minimize hydroxypropyl methylcellulose acetate succinate aggregation and minimize spray-nozzle clogging at elevated processing temperatures. The mechanisms of stabilization (i.e. charge stabilization and molecular interactions) were studied by performing zeta potential and FTIR studies. Electrostatic stabilization by sodium lauryl sulfate and hydrogen bonding by polyethylene glycol provided dispersion stability and yielded a stable aqueous coating formulation that prevented spray-nozzle clogging...
February 16, 2018: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/29458203/precision-pharmacology-for-alzheimer-s-disease
#3
REVIEW
Harald Hampel, Andrea Vergallo, Lisi Flores Aguilar, Norbert Benda, Karl Broich, A Claudio Cuello, Jeffrey Cummings, Bruno Dubois, Howard J Federoff, Massimo Fiandaca, Remy Genthon, Marion Haberkamp, Eric Karran, Mark Mapstone, George Perry, Lon S Schneider, Lindsay A Welikovitch, Janet Woodcock, Filippo Baldacci, Simone Lista
The complex multifactorial nature of polygenic Alzheimer's disease (AD) presents significant challenges for drug development. AD pathophysiology is progressing in a non-linear dynamic fashion across multiple systems levels - from molecules to organ systems - and through adaptation, to compensation, and decompensation to systems failure. Adaptation and compensation maintain homeostasis: a dynamic equilibrium resulting from the dynamic non-linear interaction between genome, epigenome, and environment. An individual vulnerability to stressors exists on the basis of individual triggers, drivers, and thresholds accounting for the initiation and failure of adaptive and compensatory responses...
February 16, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29458198/adverse-childhood-experiences-and-adult-inflammation-findings-from-the-1958-british-birth-cohort
#4
Mingyi Chen, Rebecca E Lacey
BACKGROUND: The relationship between adverse childhood experiences (ACE) and poorer health across the life course is well established. Increased chronic inflammation might be one mechanism through which these associations operate. The aim of this study was to explore the relationship between ACE and adult inflammation using a prospective longitudinal study. We also investigated whether associations were explained by life course socioeconomic, psychological and health behavioural factors, and whether associations differed by gender...
February 16, 2018: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/29458195/human-dorsal-root-ganglion-pulsed-radiofrequency-treatment-modulates-cerebrospinal-fluid-lymphocytes-and-neuroinflammatory-markers-in-chronic-radicular-pain
#5
Basabjit Das, Melissa Conroy, David Moore, Joanne Lysaght, Connail McCrory
Radicular pain is a common cause of disability. Traditionally treatment has been either epidural steroid injection providing short-term relief or surgery with associated complications. Pulsed radiofrequency (PRF) applied to the Dorsal Root Ganglion (DRG) is a minimally invasive day-care treatment, which is gaining significant clinical acceptance in a selective group of patients with pure radicular pain. Greater insights into the immunomodulatory effects of this procedure may help to further optimise its application and find alternative treatment options...
February 16, 2018: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/29458189/impact-of-time-of-day-on-diffusivity-measures-of-brain-tissue-derived-from-diffusion-tensor-imaging
#6
Cibu Thomas, Neda Sadeghi, Amrita Nayak, Aaron Trefler, Joelle Sarlls, Chris Baker, Carlo Pierpaoli
Diurnal fluctuations in MRI measures of structural and functional properties of the brain have been reported recently. These fluctuations may have a physiological origin, since they have been detected using different MRI modalities, and cannot be explained by factors that are typically known to confound MRI measures. While preliminary evidence suggests that measures of structural properties of the brain based on diffusion tensor imaging (DTI) fluctuate as a function of time-of-day (TOD), the underlying mechanism has not been investigated...
February 16, 2018: NeuroImage
https://www.readbyqxmd.com/read/29458182/a-direct-gateway-into-the-extracellular-space-unconventional-secretion-of-fgf2-through-self-sustained-plasma-membrane-pores
#7
REVIEW
Julia P Steringer, Walter Nickel
As illustrated by a diverse set of examples in this special issue, multiple mechanisms of protein secretion have been identified in eukaryotes that do not involve the endoplasmic reticulum (ER) and the Golgi apparatus. Here we focus on the type I pathway with Fibroblast Growth Factor 2 (FGF2) being the most prominent example. Unconventional secretion of FGF2 from cells is mediated by direct protein translocation across the plasma membrane. A unique feature of this process is the ability of FGF2 to form its own membrane translocation intermediate through oligomerization and membrane insertion...
February 16, 2018: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/29458180/feature-guided-attentional-capture-cannot-be-prevented-by-spatial-filtering
#8
Nick Berggren, Martin Eimer
Feature-based control processes guide attention towards objects with target features in visual search. While these processes are assumed to operate globally across the entire visual field, it remains controversial whether target-matching objects at task-irrelevant locations can be excluded from attentional selection, especially when spatial attention is already narrowly focused elsewhere. We investigated whether probe stimuli at irrelevant lateral locations capture attention when they precede search displays where targets are defined either by a specific feature (colour or orientation) or by a colour/orientation conjunction by measuring N2pc components (an electrophysiological marker of attentional target selection) to these probes...
February 16, 2018: Biological Psychology
https://www.readbyqxmd.com/read/29458176/grp78-promotes-hepatocellular-carcinoma-proliferation-by-increasing-fat10-expression-through-the-nf-%C3%AE%C2%BAb-pathway
#9
Chenglin Luo, Haixia Xiong, Leifeng Chen, Xiuxia Liu, Shubing Zou, Jiafu Guan, Kai Wang
Glucose-regulated protein 78(GRP78) and the ubiquitin-like protein FAT10 each promote proliferation in hepatocellular carcinoma(HCC). However, the relationship of GRP78 and FAT10 in HCC proliferation are still not known. In this study, we found that GRP78 and FAT10 were significantly overexpressed in HCC tissues compare with adjacent non-cancerous tissues, and a positive correlation was found between their expression and associated proliferation characteristics. High expression of GRP78 and FAT10 were positively correlated with tumor proliferation and poor prognosis in HCC...
February 16, 2018: Experimental Cell Research
https://www.readbyqxmd.com/read/29458173/deregulation-of-nrf2-are-signaling-pathway-causes-susceptibility-of-dystrophin-deficient-myotubes-to-menadione-induced-oxidative-stress
#10
Su Jin Choi, Hye Sun Kim
Duchenne muscular dystrophy (DMD) is an X chromosome-linked disorder caused by a mutation in the dystrophin gene. Many previous studies reported that the skeletal muscles of DMD patients were more susceptible to oxidative stress than those of healthy people. However, not much has been known about the responsible mechanism of the differential susceptibility. In this study, we established dystrophin knock-down (DysKD) cell lines by transfection of dystrophin shRNA lentiviral particles into C2 cells and found that DysKD myotubes are more vulnerable to menadione-induced oxidative stress than control myotubes...
February 16, 2018: Experimental Cell Research
https://www.readbyqxmd.com/read/29458171/toxicology-studies-of-furosine-in-vitro-in-vivo-and-exploration-of-the-related-mechanism
#11
Hui-Ying Li, Lei Xing, Jia-Qi Wang, Nan Zheng
AIM: Furosine is one of the Maillard reaction products (MRPs) and is found in a variety of heat-processed food. Yet its toxicity is still unclear. The present study was designed to assess furosine toxicity in cell models and in CD-1 mice, respectively. METHODS: In vitro, the effects of furosine on the cell viability, cell cycle and apoptosis (Hek293, HepG2, SK-N-SH and Caco2) were detected and evaluated, sensitive cell lines and proper dosage of furosine for further animal experiment were determined, and the mechanisms of toxicity were explored...
February 16, 2018: Toxicology Letters
https://www.readbyqxmd.com/read/29458168/apoptosis-of-enterocytes-and-nitration-of-junctional-complex-proteins-promote-alcohol-induced-gut-leakiness-and-liver-injury
#12
Young-Eun Cho, Li-Rong Yu, Mohamed A Abdelmegeed, Seong-Ho Yoo, Byoung-Joon Song
BACKGROUND & AIMS: Binge alcohol causes gut leakiness, contributing to increased endotoxemia and inflammatory liver injury, although the molecular mechanisms are still elusive. This study was aimed at investigating the roles of apoptosis of enterocytes and nitration followed by degradation of intestinal tight junction (TJ) and adherent junction (AJ) proteins in binge alcohol-induced gut leakiness. METHODS: The levels of intestinal (ileum) junctional complex proteins, oxidative stress markers and apoptosis-related proteins in rodents, T84 colonic cells and autopsied human ileums were determined by immunoblot, immunoprecipitation, immunofluorescence, and mass-spectral analyses...
February 16, 2018: Journal of Hepatology
https://www.readbyqxmd.com/read/29458164/structure-dependent-induction-of-apoptosis-by-hepatotoxic-pyrrolizidine-alkaloids-in-the-human-hepatoma-cell-line-heparg-single-versus-repeated-exposure
#13
Julia Waizenegger, Albert Braeuning, Markus Templin, Alfonso Lampen, Stefanie Hessel-Pras
Pyrrolizidine alkaloids (PA) are secondary plant compounds. PA intoxication in humans causes severe acute and chronic hepatotoxicity. However, the molecular mechanisms of PA hepatotoxicity in humans are not well understood yet. Therefore, we investigated cell death parameters in human HepaRG cells following either single (24 h) or repeated dose treatment (14 d) with structurally different PA of the retronecine (echimidine, senecionine), heliotridine (heliotrine), and otonecine type (senkirkine). After 24 h of exposure only retronecine-type PA were cytotoxic in HepaRG cells and induced apoptosis indicated by a loss of membrane asymmetry, disruption of the mitochondrial membrane potential, and increased pro-caspase and PARP cleavage...
February 16, 2018: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/29458159/strawberry-extracts-efficiently-counteract-inflammatory-stress-induced-by-the-endotoxin-lipopolysaccharide-in-human-dermal-fibroblast
#14
Massimiliano Gasparrini, Francesca Giampieri, Tamara Y Forbes-Hernandez, Sadia Afrin, Danila Cianciosi, Patricia Reboredo-Rodriguez, Alfonso Varela-Lopez, JiaoJiao Zhang, Josè L Quiles, Bruno Mezzetti, Stefano Bompadre, Maurizio Battino
A protracted pro-inflammatory state is the common denominator in the development, progression and complication of the common chronic diseases. Dietary antioxidants represent an efficient tool to counteract this inflammatory state. The aim of the present work was to evaluate the effects of strawberry extracts on inflammation evoked by E. Coli lipopolysaccharide in Human Dermal Fibroblast, by measuring reactive oxygen species production, apoptosis rate, antioxidant enzymes activity, mitochondria functionality and also investigating the molecular pathway involved in inflammatory and antioxidant response...
February 16, 2018: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/29458150/pink1-protects-auditory-hair-cells-and-spiral-ganglion-neurons-from-cisplatin-induced-ototoxicity-via-inducing-autophagy-and-inhibiting-jnk-signaling-pathway
#15
Qianqian Yang, Gaoying Sun, Haiyan Yin, Hongrui Li, Zhixin Cao, Jinghan Wang, Meijuan Zhou, Haibo Wang, Jianfeng Li
Phosphatase and tensin homologue (PTEN)-induced putative kinase 1 (PINK1) gene encodes a serine/threonine kinase, which acts as a molecular sensor of mitochondrial health necessary for mitochondrial quality control. The present study was designed to examine whether PINK1 expressed in C57BL/6 murine cochlea and HEI-OC1 cells and, if so, to investigate the possible mechanisms underlying the action of PINK1 in cisplatin-induced death of sensory hair cells (HCs) and spiral ganglion neurons (SGNs) in vitro. The expression pattern of PINK1, formation of parkin particles, and autophagy were determined by immunofluorescent staining...
February 16, 2018: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29458148/untimely-oxidative-stress-in-%C3%AE-cells-leads-to-diabetes-role-of-circadian-clock-in-%C3%AE-cell-function
#16
REVIEW
J Lee, K Ma, M Moulik, V Yechoor
Diabetes results from a loss of β-cell function. With the number of people with diabetes reaching epidemic proportions globally, understanding mechanisms that are contributing to this increasing prevalence is critical. One such factor has been circadian disruption, with shift-work, light pollution, jet-lag, increased screen time, all acting as potential contributory factors. Though circadian disruption has been epidemiologically associated with diabetes and other metabolic disorders for many decades, it is only recently that there has been a better understanding of the underlying molecular mechanisms...
February 16, 2018: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29458146/enhanced-anticancer-effects-of-scutellaria-barbata-d-don-in-combination-with-traditional-chinese-medicine-components-on-non-small-cell-lung-cancer-cells
#17
Qian Wang, Narayan Acharya, Zhongwei Liu, Xianmei Zhou, Meghan Cromie, Jia Zhu, Weimin Gao
ETHNOPHARMACOLOGICAL RELEVANCE: Experience-based herbal medicine as a complementary to modern western medicine has triggered an array of studies in quest of novel anticancer drugs. Scutellaria barbata D. Don (SB) is commonly used to treat different types of cancers, but its molecular mechanism of action is not clearly understood. In this study, we attempted to elucidate the mode of action of a traditional Chinese medicine prescription with a total of 14 components, named Lian-Jia-San-Jie-Fang (LJSJF, in Chinese), where SB works as the "principle" against non-small cell lung cancer (NSCLC) cells...
February 16, 2018: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/29458142/insufficient-radiofrequency-ablation-promotes-proliferation-of-residual-hepatocellular-carcinoma-via-autophagy
#18
Zizhuo Zhao, Jiayi Wu, Xiaodi Liu, Ming Liang, Xinchuan Zhou, Shi Ouyang, Jiyi Yao, Jinquan Wang, Baoming Luo
Radiofrequency ablation (RFA) is considered to be a potentially curative therapy for hepatocellular carcinoma (HCC). However, insufficient RFA (IRFA) can promote rapid progression of the residual tumor. The mechanisms underlying IRFA-induced tumor promotion remain poorly understood. In the present study, we have established a subcutaneous xenograft mouse model and monitored the location and extent of IRFA by dual monitoring with ultrasonography and a thermal imager. For the first time, we provide evidence of the activation of autophagic pathways in mice exposed to IRFA...
February 16, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29458134/antiviral-activity-of-pyrrole-imidazole-polyamides-against-sv40-and-bk-polyomaviruses
#19
Terri G Edwards, Chris Fisher
The ability of antiviral polyamides (AVP) to act upon polyomaviruses (PyV) was evaluated. Initial studies found that a single treatment of AVP protected SV40-infected BSC-1 cells from cytopathic effect (CPE) for as long as 11 days p.i.. AVP substantially suppressed SV40 genome copy numbers over the duration of the experiment. Immunofluorescence analysis of ataxia-telangiectasia mutated (ATM) activation and large T antigen (LTag) expression clearly demonstrated that AVP treatment at day 1 p.i. delayed the onset of productive SV40 replication by approximately 3 days, and substantially limited the infection relative to vehicle-treated controls...
February 16, 2018: Antiviral Research
https://www.readbyqxmd.com/read/29458133/artesunate-derived-monomeric-dimeric-and-trimeric-experimental-drugs-their-unique-mechanistic-basis-and-pronounced-antiherpesviral-activity
#20
Friedrich Hahn, Tony Fröhlich, Theresa Frank, Luca D Bertzbach, Stephan Kohrt, Benedikt B Kaufer, Thomas Stamminger, Svetlana B Tsogoeva, Manfred Marschall
Human cytomegalovirus (HCMV) is a major human pathogen and is associated with severe pathology, such as life-threatening courses of infection in immunocompromised individuals and neonates. Currently, antiviral therapy is still hampered by a considerable toxicity of the available drugs and induction of viral resistance. Recently, we and others reported the very potent antiviral activity of the broad antiinfective drug artesunate in vitro and in vivo. Here, we investigated further optimized analogs including monomeric, dimeric and trimeric derivatives belonging to this highly interesting chemical group of experimental drugs (sesquiterpenes/trioxanes) and compared these to the previously identified trimeric artesunate compound TF27...
February 16, 2018: Antiviral Research
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