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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/29458203/precision-pharmacology-for-alzheimer-s-disease
#2
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/29458177/colorimetric-detection-of-microrna-based-on-dnazyme-and-nuclease-assisted-catalytic-hairpin-assembly-signal-amplification
#3
Hongmei Zhang, Kuiyu Wang, Shengjun Bu, Zhongyi Li, Chuanjing Ju, Jiayu Wan
Accurate and quantitative analysis of microRNA (miRNA) expression is critical for the diagnostics and theranostics of a disease. Herein, a proof-of-concept of a colorimetric horseradish peroxidase-mimicking DNAzyme (HRP-DNAzyme) biosensor for miRNA assay based on nuclease-assisted catalytic hairpin assembly (CHA) signal amplification was demonstrated. Duplex-specific nuclease (DSN) was employed to cleave the single-stranded DNA (ssDNA) chimeric probe (CP) on the magnetic bead (MB) surface via hybridization of the CP and target miRNA...
February 16, 2018: Molecular and Cellular Probes
https://www.readbyqxmd.com/read/29458175/maintenance-of-hematopoietic-stem-and-progenitor-cells-in-fetal-intra-aortic-hematopoietic-clusters-by-the-sox17-notch1-hes1-axis
#4
Kiyoka Saito, Ikuo Nobuhisa, Kaho Harada, Satomi Takahashi, Maha Anani, Heiko Lickert, Masami Kanai-Azuma, Yoshiakira Kanai, Tetsuya Taga
The aorta-gonad-mesonephros region, from which definitive hematopoiesis first arises in midgestation mouse embryos, has intra-aortic hematopoietic clusters (IAHCs) containing hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs). We previously reported expression of the transcription factor Sox17 in IAHCs, and overexpression of Sox17 in CD45low c-KIThigh cells comprising IAHCs maintains the formation of cell clusters and their multipotency in vitro over multiple passages. Here, we demonstrate the importance of NOTCH1 in IAHC formation and maintenance of the HSC/HPC phenotype...
February 16, 2018: Experimental Cell Research
https://www.readbyqxmd.com/read/29458168/apoptosis-of-enterocytes-and-nitration-of-junctional-complex-proteins-promote-alcohol-induced-gut-leakiness-and-liver-injury
#5
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/29458152/controversies-in-endoscopic-eradication-therapy-for-barrett-s-esophagus
#6
Srinadh Komanduri, V Raman Muthusamy, Sachin Wani
Advances in Endoscopic Eradication Therapy for Barrett's Esophagus associated neoplasia have resulted in a significant paradigm shift in diagnosis and management of this complex disease. A robust body of literature critically evaluating outcomes of resection and ablative strategies has allowed gastroenterologists to make quality, evidence based decisions for their patients. Despite this progress, there are still many unanswered questions and challenges that remain. Ultimately, identification of a cost-effective screening modality, biomarkers for risk stratification, and strides to eliminate post surveillance endoscopy after EET are essential to reach our long term goal for eradication of esophageal adenocarcinoma...
February 16, 2018: Gastroenterology
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
#7
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/29458141/long-non-coding-rnas-within-the-tumour-microenvironment-and-their-role-in-tumour-stroma-cross-talk
#8
Filippo Del Vecchio, Gui Han Lee, Joamir Hawezi, Rahul Bhome, Sian Pugh, Emre Sayan, Gareth Thomas, Graham Packham, John Primrose, Martin Pichler, Alexander Mirnezami, George Calin, Marc Bullock
Long non-coding RNAs (lncRNAs) are a diverse class of RNA transcripts which have limited protein coding potential. They perform a variety of cellular functions in health, but have also been implicated during malignant transformation. A further theme in recent years is the critical role of the tumour microenvironment and the dynamic interactions between cancer and stromal cells in promoting invasion and disease progression. Whereas the contribution of deregulated lncRNAs within cancer cells has received considerable attention, their significance within the tumour microenvironment is less well understood...
February 16, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29458125/pluripotent-stem-cells-for-uncovering-the-role-of-mitochondria-in-human-brain-function-and-dysfunction
#9
REVIEW
Annika Zink, Josef Priller, Alessandro Prigione
Mitochondrial dysfunctions are a known pathogenetic mechanism of a number of neurological and psychiatric disorders. At the same time, mutations in genes encoding for components of the mitochondrial respiratory chain cause mitochondrial diseases, which commonly exhibit neurological symptoms. Mitochondria are therefore critical for the functionality of the human nervous system. The importance of mitochondria stems from their key roles in cellular metabolism, calcium handling, redox and protein homeostasis, and overall cellular homeostasis through their dynamic network...
February 16, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/29458107/wnt-receptor-signalling-in-lung-physiology-and-pathology
#10
REVIEW
Wioletta Skronska-Wasek, Reinoud Gosens, Melanie Königshoff, Hoeke Abele Baarsma
The WNT signalling cascades have emerged as critical regulators of a wide variety of biological aspects involved in lung development as well as in physiological and pathophysiological processes in the adult lung. WNTs (secreted glycoproteins) interact with various transmembrane receptors and co-receptors to activate signalling pathways that regulate transcriptional as well as non-transcriptional responses within cells. In physiological conditions, the majority of WNT receptors and co-receptors can be detected in the adult lung...
February 16, 2018: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29458074/subthalamic-nucleus-stimulation-dopaminergic-treatment-and-impulsivity-in-parkinson-s-disease
#11
Frédérique Fluchère, Borís Burle, Franck Vidal, Wery van den Wildenberg, Tatiana Witjas, Alexandre Eusebio, Jean-Philippe Azulay, Thierry Hasbroucq
BACKGROUND: Deep brain stimulation of the subthalamic nucleus (STN DBS) is known to increase response speed and lower response accuracy in Parkinson's disease (PD) patients. It has been proposed that this speed-accuracy tradeoff is due to enhanced sensitivity of the motor system to sensory information. An alternative possibility is that this effect is due to weakened suppressive processes. The two alternative interpretations can be tested by analyzing the electromyographic activity (EMG) of the response agonists when the patients perform conflict reaction time tasks...
February 16, 2018: Neuropsychologia
https://www.readbyqxmd.com/read/29458045/aldose-reductase-inhibitor-fidarestat-prevents-doxorubicin-induced-endothelial-cell-death-and-dysfunction
#12
Himangshu Sonowal, Pabitra Pal, Kirtikar Shukla, Ashish Saxena, Satish K Srivastava, Kota V Ramana
Despite doxorubicin (Dox) being one of the most widely used chemotherapy agents for breast, blood and lung cancers, its use in colon cancer is limited due to increased drug resistance and severe cardiotoxic side effects that increase mortality associated with its use at high doses. Therefore, better adjuvant therapies are warranted to improve the chemotherapeutic efficacy and to decrease cardiotoxicity. We have recently shown that aldose reductase inhibitor, fidarestat, increases the Dox-induced colon cancer cell death and reduces cardiomyopathy...
February 16, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29458042/pretreatment-with-cholesterol-loaded-cyclodextrins-prevents-loss-of-motility-associated-proteins-during-cryopreservation-of-addra-gazelle-nanger-dama-ruficollis-spermatozoa
#13
Jessye Wojtusik, Yan Wang, Budhan S Pukazhenthi
Sperm cryopreservation is challenging, often resulting in irreversible damage to spermatozoa, as indicated by decreased motility, viability, and/or acrosomal integrity. Developing cryopreservation protocols for gametes of endangered species compounds the complexity of technique optimization; samples are difficult to obtain and numbers are limited. Cryopreservation of sperm collected from the critically endangered addra gazelle (Nanger dama ruficollis), a member of the Bovidae family, resulted in significant loss of motility, which was prevented by pretreatment with cholesterol-loaded cyclodextrin (CLC)...
February 16, 2018: Cryobiology
https://www.readbyqxmd.com/read/29458011/inflammatory-cytokines-induce-podoplanin-expression-at-the-tumor-invasive-front
#14
Akiko Kunita, Vanessa Baeriswyl, Claudia Meda, Erik Cabuy, Kimiko Takeshita, Enrico Giraudo, Andreas Wicki, Masashi Fukayama, Gerhard Christofori
Tumor invasion is a critical first step in the organismic dissemination of cancer cells and the formation of metastasis in distant organs, the most important prognostic factor and the actual cause of death in most of the cancer patients. We report here that the cell surface protein podoplanin (PDPN), a potent inducer of cancer cell invasion, is conspicuously expressed by the invasive front of squamous cell carcinomas (SCC) of the cervix in patients and in the transgenic HPV/E2 mouse model of cervical cancer...
February 16, 2018: American Journal of Pathology
https://www.readbyqxmd.com/read/29458010/galectin-9-is-critical-for-mucosal-adaptive-immunity-through-the-t-h-17-iga-axis
#15
Chih-Chia Liang, Chi-Shan Li, I-Chun Weng, Huan-Yuan Chen, Hsueh-Han Lu, Chiu-Ching Huang, Fu-Tong Liu
Impairment of the intestinal mucosal immunity significantly increases the risk of acute and chronic diseases. Immunoglobulin A (IgA) plays a major role in humoral mucosal immunity to provide protection against pathogens and toxins in the gut. Here, we investigated the role of endogenous galectin-9, a tandem repeat-type β-galactoside-binding protein, in intestinal mucosal immunity. By mucosal immunization of Lgals9-/- and littermate control mice, it was found that lack of galectin-9 impaired mucosal antigen-specific IgA response in the gut...
February 16, 2018: American Journal of Pathology
https://www.readbyqxmd.com/read/29457983/antimycobacterial-effect-of-ifng-interferon-gamma-induced-autophagy-is-dependent-on-the-hmox1-heme-oxygenase-1-mediated-increase-in-the-intracellular-calcium-levels-and-modulation-of-ppp3-calcineurin-tfeb-transcription-factor-eb-axis
#16
Nisha Singh, Pallavi Kansal, Zeeshan Ahmad, Naveen Baid, Hariom Kushwaha, Neeraj Khatri, Ashwani Kumar
IFNG (interferon gamma)-induced autophagy plays an important role in the elimination of intracellular pathogens, such as Mycobacterium tuberculosis (Mtb). However, the signaling cascade that leads to the increase in autophagy flux in response to IFNG is poorly defined. Here, we demonstrate that HMOX1 (heme oxygenase 1)-generated carbon monoxide (CO) is required for the induction of autophagy and killing of Mtb residing in macrophages in response to immunomodulation by IFNG. Interestingly, IFNG exposure of macrophages induces an increase in intracellular calcium levels that is dependent on HMOX1 generated CO...
February 19, 2018: Autophagy
https://www.readbyqxmd.com/read/29457981/reversible-surface-engineering-via-nitrone-mediated-radical-coupling
#17
Joachim Laun, Wouter Marchal, Vanessa Trouillet, Alexander Welle, An T Hardy, Marlies K Van Bael, Christopher Barner-Kowollik, Tanja Junkers
Efficient and simple polymer conjugation reactions are critical for introducing functionalities on surfaces. For polymer surface grafting, post polymerization modifications are often required, which can impose a significant synthetic hurdle. Here, we report two strategies that allow for reversible surface engineering via nitrone-mediated radical coupling (NMRC). Macroradicals stemming from activation of polymers generated by copper-mediated radical polymerization are grafted via radical trapping with a surface-immobilized nitrone or a solution-borne nitrone...
February 19, 2018: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/29457950/knowledge-and-skills-of-critical-care-nurses-in-assisting-with-intubation
#18
Chris Williams, Andrew Parry
Assisting with tracheal intubation is an aspect of clinical practice that requires knowledge and skill if the procedure is to be carried out in a timely and safe manner. Maintaining this knowledge and skill requires good quality education and regular opportunities to practise. These two factors appear to be inconsistent in critical care units. This article details an audit performed on a large tertiary referral centre critical care unit. It was undertaken in two phases: the first was a self-assessment of knowledge and the second was a practical assessment of the audit subjects in a simulated setting...
February 22, 2018: British Journal of Nursing: BJN
https://www.readbyqxmd.com/read/29457920/a-critical-appraisal-of-the-reporting-quality-of-published-randomized-controlled-trials-in-the-fall-injuries
#19
Mohammad Asghari Jafarabadi, Homayoun Sadeghi-Bazrgani, Iman Dianat
To evaluate the quality of reporting in published randomized controlled trials (RTCs) in the field of fall injuries. The 188 RTCs published between 2001 and 2011, indexed in EMBASE and Medline databases were extracted through searching by appropriate keywords and EMTree classification terms. The evaluation trustworthiness was assured through parallel evaluations of two experts in epidemiology and biostatistics. About 40%-75% of papers had problems in reporting random allocation method, allocation concealment, random allocation implementation, blinding and similarity among groups, intention to treat and balancing benefits and harms...
February 19, 2018: International Journal of Injury Control and Safety Promotion
https://www.readbyqxmd.com/read/29457904/conflict-in-the-mechanism-and-kinetics-of-the-barrierless-reaction-between-sh-and-no-2-radicals
#20
Ramanpreet Kaur, Vikas
There are some unsettled issues regarding the mechanism and kinetics of an important atmospheric reaction of NO2 radical with the SH radical. The existing mechanism is based on the formation of HSO and NO radicals, both of which can result only along one barrierless channel. However, the detection of NO radical has never been reported though the formation of HSO radical has been followed in some studies to determine the rate constants. The latter are mainly obtained by monitoring the SH decay, but rate constants are reported to be highly conflicting among the existing studies reporting its value ranging from 10-10 to 10-12 cm3 molecule-1 sec-1 ...
February 19, 2018: Journal of Physical Chemistry. A
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