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https://www.readbyqxmd.com/read/28088839/pharmacokinetic-pharmacodynamic-modeling-of-the-pde4-inhibitor-tak-648-in-type-2-diabetes-early-translational-approaches-for-human-dose-prediction
#1
N Plock, S Vollert, M Mayer, G Hanauer, G Lahu
TAK-648 is a PDE4 inhibitor with demonstrated preclinical antidiabetic properties. Our objective was to develop a translational pharmacokinetic/pharmacodynamic (PK/PD) model for human type 2 diabetes (T2D) dose prediction using HbA1c results from a db/db mouse study. Estimated parameters in combination with tPDE4i values calculated for the clinical roflumilast dose of 500 μg were used to translate preclinical effects of TAK-648 to required exposure in humans. A first-in-human study with single TAK-648 doses of 0...
January 15, 2017: Clinical and Translational Science
https://www.readbyqxmd.com/read/28088838/re-evaluation-of-phenotypic-expression-in-differentiated-type-early-adenocarcinoma-of-the-stomach
#2
Masato Hayakawa, Ken Nishikura, Yoichi Ajioka, Yutaka Aoyagi, Shuji Terai
A total of 313 cases of differentiated-type early gastric adenocarcinomas, including 113 cases of small-sized carcinoma (5< × ≤10 mm) and 121 cases of microcarcinoma (0< × ≤5 mm), were examined immunohistochemically to clarify the phenotypic expressions. They were classified into four categories (gastric phenotype (G-type), intestinal phenotype, gastrointestinal phenotype, and null phenotype) by a two-step process: the phenotype based on an immunoprofile of mucin core proteins (MUCs) with CDX2 (w/...
January 15, 2017: Pathology International
https://www.readbyqxmd.com/read/28088836/upregulation-of-long-noncoding-rna-tug1-promotes-cervical-cancer-cell-proliferation-and-migration
#3
Yingying Hu, Xiangwei Sun, Chenchen Mao, Gangqiang Guo, Sisi Ye, Jianfeng Xu, Ruanmin Zou, Jun Chen, Ledan Wang, Ping Duan, Xiangyang Xue
Long noncoding RNAs (lncRNAs), a novel class of transcripts that have critical roles in carcinogenesis and progression, have emerged as important gene expression modulators. Recent evidence indicates that lncRNA taurine-upregulated gene 1 (TUG1) functions as an oncogene in numerous types of human cancers. However, its function in the development of cervical cancer remains unknown. The aim of this research was to investigate the clinical significance and biological functions of TUG1 in cervical cancer. TUG1 was found to be significantly upregulated in cervical cancer tissues and four cervical cancer cell lines by quantitative real-time polymerase chain reaction (qRT-PCR)...
January 15, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28088790/intraperitoneal-immunotherapy-with-t-cells-stably-and-transiently-expressing-anti-epcam-car-in-xenograft-models-of-peritoneal-carcinomatosis
#4
Wei Xia Ang, Zhendong Li, Zhixia Chi, Shou-Hui Du, Can Chen, Johan C K Tay, Han Chong Toh, John E Connolly, Xue Hu Xu, Shu Wang
The epithelial cell adhesion molecule (EpCAM) is overexpressed in a wide variety of tumor types, including peritoneal carcinomatosis (PC) from gastrointestinal and gynecological malignancies. To develop a chimeric antigen receptor T (CART) cell therapy approach to treat patients with end-stage PC, we constructed third generation CARs specific to EpCAM using the 4D5MOC-B single chain variable fragment. CART cells were generated with lentiviral transduction and exhibited specific in vitro killing activity against EpCAM-positive human ovarian and colorectal cancer cells...
January 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28088789/gprc5a-knockout-mouse-lung-epithelial-cells-predicts-ceruloplasmin-lipocalin-2-and-periostin-as-potential-biomarkers-at-early-stages-of-lung-tumorigenesis
#5
Beibei Sun, Wenzheng Guo, Song Hu, Feng Yao, Keke Yu, Jie Xing, Ronghua Wang, Hongyong Song, Yueling Liao, Tong Wang, Pengfei Jiang, Baohui Han, Jiong Deng
Lung cancer is the leading cause of cancer death. As most of lung cancer patients were diagnosed with the advanced stage, early detection is considered as the most effective strategy to reduce high mortality. Thus, it is desirable to identify specific biomarkers at early stages of lung tumorigenesis. GPRC5A is a lung tumor suppressor gene. GPRC5A deficiency is linked to lung cancer development. We hyposthesized that, dysregulated gene expression that results from Gprc5a deficiency may provide potential biomarkers at early stages of lung tumorigenesis...
January 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28088782/pde5-inhibitors-enhance-the-lethality-of-pemetrexed-sorafenib
#6
Laurence Booth, Jane L Roberts, Andrew Poklepovic, Paul Dent
The combination of pemetrexed and sorafenib has significant clinical activity against a wide variety of tumor types in patients and the present studies were performed to determine whether sildenafil enhances the killing potential of [pemetrexed + sorafenib]. In multiple genetically diverse lung cancer cell lines, sildenafil enhanced the lethality of [pemetrexed + sorafenib]. The three-drug combination reduced the activities of AKT, mTOR and STAT transcription factors; increased the activities of eIF2α and ULK-1; lowered the expression of MCL-1, BCL-XL, thioredoxin and SOD2; and increased the expression of Beclin1...
January 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28088779/comprehensive-proteome-analysis-of-lysosomes-reveals-the-diverse-function-of-macrophages-in-immune-responses
#7
Yanpan Gao, Yanyu Chen, Shaohua Zhan, Wenhao Zhang, Feng Xiong, Wei Ge
Phagocytosis and autophagy in macrophages have been shown to be essential to both innate and adaptive immunity. Lysosomes are the main catabolic subcellular organelles responsible for degradation and recycling of both extracellular and intracellular material, which are the final steps in phagocytosis and autophagy. However, the molecular mechanisms underlying lysosomal functions after infection remain obscure. In this study, we conducted a quantitative proteomics analysis of the changes in constitution and glycosylation of proteins in lysosomes derived from murine RAW 264...
January 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28088766/staphylococcus-aureus-cc395-harbours-a-novel-composite-staphylococcal-cassette-chromosome-mec-element
#8
Jesper Larsen, Paal S Andersen, Volker Winstel, Andreas Peschel
BACKGROUND: CoNS species are likely reservoirs of the staphylococcal cassette chromosome mec (SCCmec) in Staphylococcus aureus S aureus CC395 is unique as it is capable of exchanging DNA with CoNS via bacteriophages, which are also known to mediate transfer of SCCmec OBJECTIVES: To analyse the structure and putative origin of the SCCmec element in S aureus CC395. METHODS: The only MRSA CC395 strain described in the literature, JS395, was subjected to WGS, and its SCCmec element was compared with those found in CoNS species and other S...
January 14, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28088749/dual-channel-probe-of-carbon-dots-cooperating-with-gold-nanoclusters-employed-for-assaying-multiple-targets
#9
Kuncheng Yang, Shanshan Wang, Yingyi Wang, Hong Miao, Xiaoming Yang
Herein, carbon dots (CD@Papain) from papain have been originally synthesized in aqueous solution along with a quantum yield of 6.2%, and showed cyan fluorescence at 435nm. Meanwhile, papain-templated Au nanoclusters (AuNCs@Papain) were prepared with the same precursor. On the basis of the two types of nanomaterials, CD@Papain and AuNCs@Papain have been designed to assemble as one nanosensor (termed as CD-AuNCs@Papain) through a typical cross-linking reaction. Significantly, it not only emitted the dual-emission fluorescent signals with the same excitation, but also can assay multiple targets through exhibiting cyan, yellow, and red emission respectively...
January 7, 2017: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/28088714/children-s-and-adults-use-of-verbal-information-to-visually-anticipate-others-actions-a-study-on-explicit-and-implicit-social-cognitive-processing
#10
Markus Paulus, Tobias Schuwerk, Beate Sodian, Kerstin Ganglmayer
According to recent theories, social cognition is based on two different types of information-processing; an implicit or action-based one and an explicit or verbal one. The present study examined whether implicit and explicit social-cognitive information processing interact with each other by investigating young children's and adults' use of verbal (i.e., explicit) information to predict others' actions. Employing eye-tracking to measure anticipatory eye-movements as a measure of implicit processing, Experiment 1 presented 1...
January 12, 2017: Cognition
https://www.readbyqxmd.com/read/28088710/short-range-shooting-distance-estimation-using-variable-pressure-sem-images-of-the-surroundings-of-bullet-holes-in-textiles
#11
Ruth Hinrichs, Paulo Ricardo Ost Frank, M A Z Vasconcellos
Modifications of cotton and polyester textiles due to shots fired at short range were analyzed with a variable pressure scanning electron microscope (VP-SEM). Different mechanisms of fiber rupture as a function of fiber type and shooting distance were detected, namely fusing, melting, scorching, and mechanical breakage. To estimate the firing distance, the approximately exponential decay of GSR coverage as a function of radial distance from the entrance hole was determined from image analysis, instead of relying on chemical analysis with EDX, which is problematic in the VP-SEM...
December 29, 2016: Forensic Science International
https://www.readbyqxmd.com/read/28088706/topological-imaging-in-bounded-elastic-media
#12
Emma Lubeigt, Serge Mensah, Sandrine Rakotonarivo, Jean-François Chaix, François Baqué, Gilles Gobillot
Detecting, imaging and sizing defects in a bounded elastic medium is still a difficult task, especially when access is complex. Adjoint methods simplify the task as they take advantage of prior information such as the geometry and material properties. However, they still reveal a number of important limitations. Artifacts observed on the conventional topological energy image result from wave interactions with the boundaries of the inspected medium. The paper describes a method for addressing these artifacts, which involves forward and adjoint fields specified in terms of the boundary conditions...
January 4, 2017: Ultrasonics
https://www.readbyqxmd.com/read/28088699/procyanidin-b2-gallates-inhibit-ifn-%C3%AE-and-il-17-production-in-t-cells-by-suppressing-t-bet-and-ror%C3%AE-t-expression
#13
Sachi Tanaka, Kanon Furuya, Kana Yamamoto, Kazuki Yamada, Mikihiro Ichikawa, Manato Suda, Hidefumi Makabe
Procyanidins are widely found in plants and have anti-inflammatory activities. Procyanidin B2 (PCB2) inhibits production of proinflammatory cytokines in macrophages. However, there has been no study that has attempted to determine the effects of PCB2 gallates on T cell functions. In the present study, murine splenocytes were isolated and treated with PCB2 or PCB2 gallates in the presence of an anti-CD3 monoclonal antibody (mAb). PCB2 gallates, but not PCB2, inhibited proliferation and T cell activation of splenocytes after stimulation with the anti-CD3 mAb...
January 12, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28088698/metformin-enhancing-the-antitumor-efficacy-of-carboplatin-against-ehrlich-solid-carcinoma-grown-in-diabetic-mice-effect-on-igf-1-and-tumoral-expression-of-igf-1-receptors
#14
Dina M Abo-Elmatty, Eman A Ahmed, Mona K Tawfik, Seham A Helmy
Diabetes has been listed as a risk factor for various types of cancer. Cancer cell development can be promoted by increased levels of IGF-1 and hyperinsulinemia that are associated with diabetes type II. Metformin is an anti-diabetic agent and its potential antitumor impact has become the objective of numerous studies. In this vein, we hypothesize that using metformin in diabetes type II mice may synergistic with carboplatin for reducing the risk of cancer. Therefore, the study aimed to evaluate the in vivo antitumor activity of metformin against solid EAC tumor growth in female diabetic mice and its potential pro-apoptotic and anti-proliferative effects with clarification of its inconclusive biological mechanisms...
January 12, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28088694/metabolic-network-modeling-with-model-organisms
#15
REVIEW
L Safak Yilmaz, Albertha Jm Walhout
Flux balance analysis (FBA) with genome-scale metabolic network models (GSMNM) allows systems level predictions of metabolism in a variety of organisms. Different types of predictions with different accuracy levels can be made depending on the applied experimental constraints ranging from measurement of exchange fluxes to the integration of gene expression data. Metabolic network modeling with model organisms has pioneered method development in this field. In addition, model organism GSMNMs are useful for basic understanding of metabolism, and in the case of animal models, for the study of metabolic human diseases...
January 12, 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/28088669/micro-mechanical-properties-of-the-tendon-to-bone-attachment
#16
Alix C Deymier, Yiran An, John J Boyle, Andrea G Schwartz, Victor Birman, Guy M Genin, Stavros Thomopoulos, Asa H Barber
: The tendon-to-bone attachment (enthesis) is a complex hierarchical tissue that connects stiff bone to compliant tendon. The attachment site at the micrometer scale exhibits gradients in mineral content and collagen orientation, which likely act to minimize stress concentrations. The physiological micromechanics of the attachment thus define resultant performance, but difficulties in sample preparation and mechanical testing at this scale have restricted understanding of structure-mechanical function...
January 11, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28088667/cell-laden-hydrogels-for-osteochondral-and-cartilage-tissue-engineering
#17
REVIEW
Jingzhou Yang, Yu Shrike Zhang, Kan Yue, Ali Khademhosseini
: Despite tremendous advances in the field of regenerative medicine, it still remains challenging to repair the osteochondral interface and full-thickness articular cartilage defects. This inefficiency largely originates from the lack of appropriate tissue engineered artificial matrices that can replace the damaged regions and promote tissue regeneration. Hydrogels are emerging as a promising class of biomaterials for both soft and hard tissue regeneration. Many critical properties of hydrogels, such as mechanical stiffness, elasticity, water content, bioactivity, and degradation, can be rationally designed and conveniently tuned by proper selection of the material and chemistry...
January 11, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28088662/metabolic-profiles-of-exudates-from-chronic-leg-ulcerations
#18
Adam Junka, Wojciech Wojtowicz, Adam Ząbek, Grzegorz Krasowski, Danuta Smutnicka, Barbara Bakalorz, Agnieszka Boruta, Mariusz Dziadas, Piotr Młynarz, Parish Paymon Sedghizadeh, Marzenna Bartoszewicz
Chronic leg ulceration is a disease usually associated with other comorbidities, and significantly reduces patient quality of life. Infected leg ulcers can lead to limb-threatening sequelae or mortality. Leg ulcerations are colonized by a number of microbes that are able to cause life-threating infections in susceptible patients. Wound exudate is a body fluid that collects metabolites from patient eukaryotic cells and from prokaryotic bacterial communities inhabiting the wound. This study aimed at identification of metabolites in exudates collected from chronic leg ulcers, and correlation of this metabolome with patient comorbidities and microbiological status of the wound...
January 10, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28088654/transcriptional-response-of-skeletal-muscle-to-a-low-protein-perinatal-diet-in-rat-offspring-at-different-ages-the-role-of-key-enzymes-of-glucose-fatty-acid-oxidation
#19
José Luiz de Brito Alves, Ana Elisa Toscano, João Henrique da Costa-Silva, Hubert Vidal, Carol Góis Leandro, Luciano Pirola
Skeletal muscle is a plastic tissue during development with distinctive acute and chronic response to maternal protein restriction. This study evaluated gene and protein expression of key-enzymes of glycolytic pathway (HK2, PFK, PDK4 and CS), and fatty acid oxidation (CPT1 and β-HAD) of two different types of skeletal muscle [soleus and extensor digitorium longus (EDL)] from offspring rats at 30 and 90 days of age, exposed to maternal isoenergetic low protein diet throughout gestation and lactation. Pups from dams fed 17% protein diet (n=5, normal protein, Np), and low protein pups from dams fed 8% casein diet (low protein, Lp, n=5) were evaluated...
December 15, 2016: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28088646/bone-microarchitecture-in-adolescent-boys-with-autism-spectrum-disorder
#20
Ann M Neumeyer, Natalia Cano Sokoloff, Erin McDonnell, Eric A Macklin, Christopher J McDougle, Madhusmita Misra
BACKGROUND: Boys with autism spectrum disorder (ASD) have lower areal bone mineral density (aBMD) than typically developing controls (TDC). Studies of volumetric BMD (vBMD) and bone microarchitecture provide information about fracture risk beyond that provided by aBMD but are currently lacking in ASD. OBJECTIVES: To assess ultradistal radius and distal tibia vBMD, bone microarchitecture and strength estimates in adolescent boys with ASD compared to TDC. DESIGN/METHODS: Cross-sectional study of 34 boys (16 ASD, 18 TDC) that assessed (i) aBMD at the whole body (WB), WB less head (WBLH), hip and spine using dual X-ray absorptiometry (DXA), (ii) vBMD and bone microarchitecture at the ultradistal radius and distal tibia using high-resolution peripheral quantitative CT (HRpQCT), and (iii) bone strength estimates (stiffness and failure load) using micro-finite element analysis (FEA)...
January 11, 2017: Bone
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