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https://www.readbyqxmd.com/read/28107773/safety-and-effectiveness-of-tofogliflozin-in-elderly-japanese-patients-with-type-2-diabetes-mellitus-a-post-marketing-study-j-step-el-study
#1
Kazunori Utsunomiya, Naoki Shimmoto, Masayuki Senda, Yuji Kurihara, Ryoji Gunji, Shoko Fujii, Seigo Kakiuchi, Hisataka Fujiwara, Hiroyuki Kameda, Masahiro Tamura, Kohei Kaku
AIMS/INTRODUCTION: While sodium glucose cotransporter 2 inhibitors are a promising treatment for type 2 diabetes mellitus, they are associated with concerns about specific adverse drug reactions. We conducted a 1-year post-marketing study of tofogliflozin, a novel agent in this class, in Japanese elderly patients with type 2 diabetes mellitus. MATERIALS AND METHODS: This was a prospective, observational, and multicenter post-marketing study conducted in the context of routine clinical practice...
January 20, 2017: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/28107768/arabidopsis-protein-s-acyl-transferase4-mediates-root-hair-growth
#2
Zhi-Yuan Wan, Sen Chai, Fu-Rong Ge, Qiang-Nan Feng, Yan Zhang, Sha Li
Polar growth of root hairs is critical for plant survival and necessitates fine-tuned ROP signaling. Multiple ROP regulators participate in root hair growth. However, protein S-acyl transferases (PATs), mediating the S-acylation and membrane partitioning of ROPs, are yet to be found. By using a reverse genetic approach, combining fluorescence probes, pharmacological drugs, site-directed mutagenesis, and genetic analysis with related root-hair mutants, we have identified and characterized an Arabidopsis PAT, which may be responsible for ROP2 S-acylation in root hairs...
January 20, 2017: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/28107674/mitochondrial-serine-hydroxymethyltransferase-2-is-a-potential-diagnostic-and-prognostic-biomarker-for-human-glioma
#3
Bo Wang, Wei Wang, ZhiZhong Zhu, XueBin Zhang, Fan Tang, Dong Wang, Xi Liu, XiaoLing Yan, Hao Zhuang
OBJECTIVE: Scholars have gradually come to appreciate the relevance of serine and glycine metabolism. Recently, researchers have discovered that mitochondrial serine hydroxymethyltransferase 2 (SHMT2) is overexpressed in various types of cancer. However, the function of SHMT2 in glioma is not clear. In this study, we sought to examine the expression of SHMT2 in glioma, the association between SHMT2 expression and clinicopathological characteristics, and the association of SHMT2 expression with prognosis in glioma patients...
January 16, 2017: Clinical Neurology and Neurosurgery
https://www.readbyqxmd.com/read/28107651/one-ring-to-fight-them-all-the-sulfazecin-story
#4
Daniel Braga, Gerald Lackner
In this issue of Cell Chemical Biology, Li et al. (2017) report on the biosynthesis of the monobactam sulfazecin by Pseudomonas acidophila and hypothesize a novel mechanism of β-lactam ring formation. As monobactam antibiotics are unaffected by some emerging resistance mechanisms (particularly metallo-β-lactamases), this discovery opens prospects to engineer β-lactam antibiotics against multi-drug resistant pathogens.
January 19, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28107543/quantification-of-pulmonary-fibrosis-in-a-bleomycin-mouse-model-using-automated-histological-image-analysis
#5
Jean-Claude Gilhodes, Yvon Julé, Sebastian Kreuz, Birgit Stierstorfer, Detlef Stiller, Lutz Wollin
Current literature on pulmonary fibrosis induced in animal models highlights the need of an accurate, reliable and reproducible histological quantitative analysis. One of the major limits of histological scoring concerns the fact that it is observer-dependent and consequently subject to variability, which may preclude comparative studies between different laboratories. To achieve a reliable and observer-independent quantification of lung fibrosis we developed an automated software histological image analysis performed from digital image of entire lung sections...
2017: PloS One
https://www.readbyqxmd.com/read/28107358/modeling-an-excitable-biosynthetic-tissue-with-inherent-variability-for-paired-computational-experimental-studies
#6
Tanmay A Gokhale, Jong M Kim, Robert D Kirkton, Nenad Bursac, Craig S Henriquez
To understand how excitable tissues give rise to arrhythmias, it is crucially necessary to understand the electrical dynamics of cells in the context of their environment. Multicellular monolayer cultures have proven useful for investigating arrhythmias and other conduction anomalies, and because of their relatively simple structure, these constructs lend themselves to paired computational studies that often help elucidate mechanisms of the observed behavior. However, tissue cultures of cardiomyocyte monolayers currently require the use of neonatal cells with ionic properties that change rapidly during development and have thus been poorly characterized and modeled to date...
January 20, 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28107182/the-nitrobenzoxadiazole-derivative-mc3181-blocks-melanoma-invasion-and-metastasis
#7
Anastasia De Luca, Debora Carpanese, Maria Cristina Rapanotti, Tara Mayte Suarez Viguria, Maria Antonietta Forgione, Dante Rotili, Chiara Fulci, Egidio Iorio, Luigi Quintieri, Sergio Chimenti, Luca Bianchi, Antonio Rosato, Anna Maria Caccuri
The novel nitrobenzoxadiazole (NBD) derivative MC3181 is endowed with remarkable therapeutic activity in mice bearing both sensitive and vemurafenib-resistant human melanoma xenografts. Here, we report that subtoxic concentrations of this compound significantly reduced invasiveness of BRAF-V600D mutated WM115 and WM266.4 melanoma cell lines derived from the primary lesion and related skin metastasis of the same patient, respectively. The strong antimetastatic activity of MC3181 was observed in both 2D monolayer cultures and 3D multicellular tumor spheroids, and confirmed in vivo by the significant decrease in the number of B16-F10 melanoma lung metastases in drug-treated mice...
January 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28106982/a-novel-iron-ii-preferring-dopamine-agonist-chelator-as-potential-symptomatic-and-neuroprotective-therapeutic-agent-for-parkinson-s-disease
#8
Banibrata Das, Ashoka Kandegedara, Liping Xu, Tamara Antonio, Timothy L Stemmler, Maarten E A Reith, Aloke K Dutta
Parkinson's disease (PD) is a progressive neurodegenerative disorder and development of disease-modifying treatment is still an unmet medical need. Considering the implication of free iron (II) in PD, we report here the design and characterization of a novel hybrid iron chelator, (-)-12 (D-607) as a multitarget-directed ligand against PD. Binding and functional assays at dopamine D2/D3 receptors indicate potent agonist activity of (-)-12. The molecule displayed an efficient preferential iron (II) chelation properties along with potent in vivo activity in a reserpinized PD animal model...
January 20, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28106785/ketamine-analog-methoxetamine-induced-inflammation-and-dysfunction-of-bladder-in-rats
#9
Qiang Wang, Qinghui Wu, Junpeng Wang, Yang Chen, Guihao Zhang, Jiawei Chen, Jie Zhao, Peng Wu
The novel synthetic psychoactive ketamine analog methoxetamine is reportedly being used for recreational purposes. As ketamine use can result in urinary dysfunction, we conducted the present study to investigate how methoxetamine affects the bladder. A cystometry investigation showed that female Sprague-Dawley rats experienced increased micturition frequency bladder dysfunction after receiving a daily intraperitoneal injection of 30 mg/kg methoxetamine or ketamine for periods of 4 or 12 weeks. Histologic examinations of rat bladder tissue revealed damaged urothelium barriers, as well as evidence of inflammatory cell infiltration and matrix deposition...
January 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28106782/from-clinical-standards-to-translating-next-generation-sequencing-research-into-patient-care-improvement-for-hepatobiliary-and-pancreatic-cancers
#10
REVIEW
Ioannis D Kyrochristos, Georgios K Glantzounis, Demosthenes E Ziogas, Ioannis Gizas, Dimitrios Schizas, Efstathios G Lykoudis, Evangelos Felekouras, Anastasios Machairas, Christos Katsios, Theodoros Liakakos, William C Cho, Dimitrios H Roukos
Hepatobiliary and pancreatic (HBP) cancers are associated with high cancer-related death rates. Surgery aiming for complete tumor resection (R0) remains the cornerstone of the treatment for HBP cancers. The current progress in the adjuvant treatment is quite slow, with gemcitabine chemotherapy available only for pancreatic ductal adenocarcinoma (PDA). In the advanced and metastatic setting, only two targeted drugs have been approved by the Food & Drug Administration (FDA), which are sorafenib for hepatocellular carcinoma and erlotinib for PDA...
January 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28106753/naphthalimides-selectively-inhibit-the-activity-of-bacterial-replicative-dna-ligases-and-display-bactericidal-effects-against-tubercle-bacilli
#11
Malgorzata Korycka-Machala, Marcin Nowosielski, Aneta Kuron, Sebastian Rykowski, Agnieszka Olejniczak, Marcin Hoffmann, Jaroslaw Dziadek
The DNA ligases, enzymes that seal breaks in the backbones of DNA, are essential for all organisms, however bacterial ligases essential for DNA replication use β-nicotinamide adenine dinucleotide as their co-factor, whereas those that are essential in eukaryotes and viruses use adenosine-5'-triphosphate. This fact leads to the conclusion that NAD⁺-dependent DNA ligases in bacteria could be targeted by their co-factor specific inhibitors. The development of novel alternative medical strategies, including new drugs, are a top priority focus areas for tuberculosis research due to an increase in the number of multi-drug resistant as well as totally drug resistant tubercle bacilli strains...
January 17, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28106556/an-improved-drugs-screening-system-reveals-that-baicalein-ameliorates-the-a%C3%AE-ampa-nmda-induced-depolarization-of-neurons
#12
Tian-Syuan Lin, Han-Jung Tsai, Chih-Han Lee, Yan-Qing Song, Rih-Sheng Huang, Hsiu-Mei Hsieh-Li, Mei-Chih Liang, Yenshou Lin
The presence of amyloid-β (Aβ) plaque and tau protein hyperphosphorylation in brain tissue is the pathological hallmark of Alzheimer's disease (AD). At least some Aβ neurotoxicity is caused by the presence of excess glutamate that has been induced by Aβ accumulation. Memantine is currently the only NMDA receptor inhibitor approved for treating moderate-to-severe AD patients. We utilized primary cortical neurons and DiBAC4(3), a slow-response voltage sensitive fluorescence dye, to create a novel system for screening herbal medicines that allows the identification of pure compounds able to ameliorate Aβ-induced abnormal depolarization...
January 18, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28106485/management-strategies-for-atrial-fibrillation
#13
Peysh A Patel, Noman Ali, Andrew Hogarth, Muzahir H Tayebjee
Atrial fibrillation is the most prevalent cardiac arrhythmia, affecting 10% of those aged over 80 years. Despite multiple treatment options, it remains an independent prognostic marker of mortality due to its association with clinical sequelae, particularly cerebrovascular events. Management can be broadly divided into treatment of the arrhythmia, via rhythm or rate control, and stroke thromboprophylaxis via anticoagulation. Traditional options for pharmacotherapy include negatively chronotropic drugs such as β-blockers, and/or arrhythmia-modifying drugs such as amiodarone...
January 2017: Journal of the Royal Society of Medicine
https://www.readbyqxmd.com/read/28106378/cell-selective-apoptosis-induced-by-polymorphic-alteration-of-self-assembled-silica-nano-webs
#14
Meysam Keshavarz, Bo Tan, Krishnan Venkatakrishnan
The biocompatibility of silicon-based nanomaterial makes it suitable for biophysical and biomedical applications. However, the application of silicon-based nanomaterials has been mainly restricted to nanoparticles (NPs) as a potential drug carrier and the extracellular matrix (ECM) as a platform for cell adhesion and proliferation. Here, we introduced silica NPs self-assembled into a 3D nano-web architecture that was shown to inherit the therapeutic and proliferative attributes of both NPs and ECMs. The self-assembled silica nano-web (SNW) has, therefore, not only shown targeted drug-like behavior in HeLa cells without the use of bio-markers but also has shown ECM characteristics...
January 20, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28106369/sponge-like-porous-silica-nanosheets-from-soft-molecular-trapping-to-dna-delivery
#15
Qingmin Ji, Tomohiko Yamazaki, Jiao Sun, Żaneta Górecka, Nien-Chi Huang, Shan-Hui Hsu, Lok Kumar Shrestha, Jonathan P Hill, Katsuhiko Ariga
Sponge-like porous silica nanosheets having nanometer thicknesses and possess pores whose diameters are on the hundreds-of-nanometers scale have been used as a novel carrier for molecular immobilization of different guests. Enhanced properties of encapsulation were shown for drug molecules of different dimensions due to "softness" caused by the specific nanometric features of the porous structure. The encapsulating effect of the structure results in sustained and stimuli-responsive release behavior of immobilized guest molecules...
January 20, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28106223/next-generation-of-network-medicine-interdisciplinary-signaling-approaches
#16
REVIEW
Tamas Korcsmaros, Maria Victoria Schneider, Giulio Superti-Furga
In the last decade, network approaches have transformed our understanding of biological systems. Network analyses and visualizations have allowed us to identify essential molecules and modules in biological systems, and improved our understanding of how changes in cellular processes can lead to complex diseases, such as cancer, infectious and neurodegenerative diseases. "Network medicine" involves unbiased large-scale network-based analyses of diverse data describing interactions between genes, diseases, phenotypes, drug targets, drug transport, drug side-effects, disease trajectories and more...
January 20, 2017: Integrative Biology: Quantitative Biosciences From Nano to Macro
https://www.readbyqxmd.com/read/28105850/next-generation-tau-models-in-alzheimer-s%C3%A2-disease-research-virus-based-gene-delivery-systems
#17
V Cubinková, B Valachová, V Brezovaková, R Szabó, I Zimová, Z Kostecká, S Jadhav
Alzheimer's disease (AD) the most common form of dementia is characterized by cognitive decline and progressive loss of neurons in the central nervous system. Despite huge scientific progress, there are only few animal models that recapitulate at least majority of the AD pathology and related symptomatology. Therefore, alternative methods to develop animal models for neurodegenerative diseases are constantly explored. Recently, recombinant adeno-associated viruses (AAVs) are widely used viral vectors in development of novel models for neurodegenerative diseases...
January 19, 2017: Acta Virologica
https://www.readbyqxmd.com/read/28105822/functional-group-coverage-and-conversion-quantification-in-nanostructured-silica-by-1-h-nmr
#18
Carina I C Crucho, Carlos Baleizão, José Paulo S Farinha
Silica nanostructured materials are important in many fields, including catalysis, imaging, and drug delivery, mainly due to the versatility of surface functionalization that can bestow a huge variety of chemical and physical properties. With most applications requiring precise control over this surface modification, characterization of surface composition and reactivity have become of extreme importance. We present a novel approach to track silica surface modification and quantify functional group coverage using only solution NMR...
January 3, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28105791/the-future-of-pleiotropic-therapy-in-heart-failure-lessons-from-the-benefits-of-exercise-training-on-endothelial-function
#19
REVIEW
Gilles W De Keulenaer, Vincent F M Segers, Faiez Zannad, Dirk L Brutsaert
A novel generation of drugs is introduced in the treatment of heart failure (HF). These drugs, including phosphodiesterase-5 inhibitors, guanylate cyclase stimulators and activators, share the feature that their action is either endothelial-mediated or substitutes for endothelial pathways, in particular the nitric oxide-cyclic guanosine monophosphate pathway, thereby influencing homeostatic balances in virtually each organ system in a pleiotropic fashion. Unfortunately, recent clinical trials with some of these drugs have shown disappointing results, at least in the setting of HF with a preserved ejection fraction...
January 19, 2017: European Journal of Heart Failure
https://www.readbyqxmd.com/read/28105588/nogo-a-antibodies-for-progressive-multiple-sclerosis
#20
Benjamin V Ineichen, Patricia S Plattner, Nicolas Good, Roland Martin, Michael Linnebank, Martin E Schwab
Most of the current therapies, as well as many of the clinical trials, for multiple sclerosis (MS) target the inflammatory autoimmune processes, but less than 20% of all clinical trials investigate potential therapies for the chronic progressive disease stage of MS. The latter is responsible for the steadily increasing disability in many patients, and there is an urgent need for novel therapies that protect nervous system tissue and enhance axonal growth and/or remyelination. As outlined in this review, solid pre-clinical data suggest neutralization of the neurite outgrowth inhibitor Nogo-A as a potential new way to achieve both axonal and myelin repair...
January 19, 2017: CNS Drugs
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