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https://www.readbyqxmd.com/read/28535507/cardiac-cell-therapies-for-the-treatment-of-acute-myocardial-infarction-a-meta-analysis-from-mouse-studies
#1
Cajetan Immanuel Lang, Markus Wolfien, Anne Langenbach, Paula Müller, Olaf Wolkenhauer, Arash Yavari, Hüseyin Ince, Gustav Steinhoff, Bernd Joachim Krause, Robert David, Änne Glass
AIMS: Stem cell-based regenerative therapies for the treatment of ischemic myocardium are currently a subject of intensive investigation. A variety of cell populations have been demonstrated to be safe and to exert some positive effects in human Phase I and II clinical trials, however conclusive evidence of efficacy is still lacking. While the relevance of animal models for appropriate pre-clinical safety and efficacy testing with regard to application in Phase III studies continues to increase, concerns have been expressed regarding the validity of the mouse model to predict clinical results...
May 25, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28535504/long-non-coding-rna-kcnq1ot1-promotes-cataractogenesis-via-mir-214-and-activation-of-the-caspase-1-pathway
#2
Xin Jin, Hao Jin, Yan Shi, Yiyuan Guo, Hong Zhang
BACKGROUND/AIMS: KCNQ1OT1 regulates the expression of tissue-specific imprinted genes within the Kcnq1 domain. Imprinted genes are positive regulators of apoptosis, one of the forms of cell death related to cataract formation, and thus may provide novel therapeutic targets for cataract treatment. Here, we studied the role of non-coding RNAs(ncRNA) in cataract formation. METHODS: Human lens epithelium cells (HLECs) were treated with H2O2, and the expression of KCNQ1OT1 and miR-214 was detected by qRT-PCR...
May 25, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28535470/pharmacophore-guided-discovery-of-small-molecule-interleukin-15-inhibitors
#3
Barbara Żyżyńska-Granica, Bartosz Trzaskowski, Szymon Niewieczerzał, Sławomir Filipek, Oliwia Zegrocka-Stendel, Małgorzata Dutkiewicz, Piotr Krzeczyński, Magdalena Kowalewska, Katarzyna Koziak
Upregulation of interleukin 15 (IL-15) contributes directly i.a. to the development of inflammatory and autoimmune diseases. Selective blockade of IL-15 aimed to treat rheumatoid arthritis, psoriasis and other IL-15-related disorders has been recognized as an efficient therapeutic method. The aim of the study was to identify small molecules which would interact with IL-15 or its receptor IL-15Rα and inhibit the cytokine's activity. Based on the crystal structure of IL-15Rα·IL-15, we created pharmacophore models to screen the ZINC database of chemical compounds for potential IL-15 and IL-15Rα inhibitors...
May 12, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28535451/a-novel-carbohydrate-labeling-method-utilizing-transfer-hydrogenation-mediated-reductive-amination
#4
Zsuzsanna Kovács, Gábor Papp, Henrietta Horváth, Ferenc Joó, András Guttman
One of the most frequently used high-resolution glycan analysis methods in the biopharmaceutical and biomedical fields is capillary electrophoresis with laser-induced fluorescence (CE-LIF) detection. Glycans are usually labeled by reductive amination with a charged fluorophore containing a primary amine, which reacts with the aldehyde group at the reducing end of the glycan structures. In this reaction, first a Schiff base is formed that is reduced to form a stable conjugate by a hydrogenation reagent, such as sodium cyanoborohydride...
May 13, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28535293/invited-commentary-a-landmark-study-launched-in-a-public-health-maelstrom
#5
Eric A Engels, Charles S Rabkin, James J Goedert
The acquired immune deficiency syndrome (AIDS) epidemic was first recognized in 1981, and it quickly became a public health emergency. In a 1987 paper in the American Journal of Epidemiology (Am J Epidemiol. 1987;126(2): 310-318), Richard Kaslow et al. described the launch of the Multicenter AIDS Cohort Study (MACS), a cohort study of homosexual men in 4 US cities, the purpose of which was to better understand the natural history of AIDS and its determinants. The MACS enrolled participants through a range of community contacts...
May 23, 2017: American Journal of Epidemiology
https://www.readbyqxmd.com/read/28535267/the-plasma-and-mucosal-igm-iga-and-igg-responses-to-the-vibrio-cholerae-o1-protein-immunome-in-adults-with-cholera-in-bangladesh
#6
Richelle C Charles, Rie Nakajima, Li Liang, Al Jasinskas, Amanda Berger, Daniel T Leung, Meagan Kelly, Peng Xu, Pavol Kovác, Samantha R Giffen, James D Harbison, Fahima Chowdhury, Ashraful I Khan, Stephen B Calderwood, Taufiqur Rahman Bhuiyan, Jason B Harris, Philip L Felgner, Firdausi Qadri, Edward T Ryan
Background.: Cholera is a severe dehydrating illness of humans caused by toxigenic strains of Vibrio cholerae O1 or O139. Identification of immunogenic V. cholerae antigens could lead to a better understanding of protective immunity in human cholera. Methods.: We probed microarrays containing 3652 V. cholerae antigens with plasma and antibody-in-lymphocyte supernatant (ALS, a surrogate marker of mucosal immune responses) from patients with severe cholera caused by V...
May 23, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28535116/is-mannitol-the-treatment-of-choice-for-patients-with-ciguatera-fish-poisoning
#7
Michael E Mullins, Robert S Hoffman
CONTEXT: Ciguatera fish poisoning arises primarily from consumption of carnivorous reef fish caught in tropical and sub-tropical waters. Ciguatoxins, a class of tasteless, heat-stable, polycyclic toxins produced by dinoflagellates, accumulate through the food chain and concentrate in various carnivorous fish, such as groupers, barracudas, wrasses, amberjack, kingfishes, and eels. Characteristics of ciguatera fish poisoning include early nausea, vomiting, and diarrhea in the first one to two days post ingestion, followed by the appearance of sensory disturbances...
May 23, 2017: Clinical Toxicology
https://www.readbyqxmd.com/read/28535013/htert-c250t-promoter-mutation-and-telomere-length-as-a-molecular-markers-of-cancer-progression-in-patients-with-head-and-neck-cancer
#8
Wojciech Barczak, Wiktoria M Suchorska, Agnieszka Sobecka, Karolina Bednarowicz, Piotr Machczynski, Pawel Golusinski, Blazej Rubis, Michal M Masternak, Wojciech Golusinski
Squamous cell carcinoma of the head and neck (HNSCC) is the sixth leading cause of cancer worldwide, representing over half a million incidents every year. Cancer cells, including HNSCC, are characterized by increased telomerase activity. This enzymatic complex is active in ~90% of all cancer types and is responsible for the lengthening of telomeres. Highly recurrent point mutations in the human telomerase reverse transcriptase (hTERT) promoter have recently been reported in a number of human neoplasms. The aim of the present study was to analyze the prevalence of the hTERT promoter C250T mutation and telomere length in the blood leukocytes of 61 patients with HNSCC and 49 healthy individuals...
May 17, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28534999/mir-370-regulates-cell-proliferation-and-migration-by-targeting-egfr-in-gastric-cancer
#9
Tao Ning, Haiyang Zhang, Xinyi Wang, Shuang Li, Le Zhang, Ting Deng, Likun Zhou, Rui Liu, Xia Wang, Ming Bai, Shaohua Ge, Hongli Li, Dingzhi Huang, Guoguang Ying, Yi Ba
Epidermal growth factor receptor (EGFR) is known to be overexpressed in ~30% of gastric cancer (GC) cases, and may serve as an effective biomarker for predicting the clinical benefit of anti-EGFR therapy. However, the mechanism underlying the regulation of EGFR expression remains unknown. Evidence indicates that post-transcriptional regulation may exist in the process of EGFR expression. In the present study, we aimed to explore whether miR-370 is involved in this process, and how it impacts the biological behaviors of GC cells...
May 23, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28534988/p21-activated-protein-kinase-1-induces-the-invasion-of-gastric-cancer-cells-through-c-jun-nh2-terminal-kinase-mediated-activation-of-matrix-metalloproteinase-2
#10
Liang-Hui Li, Guo-Yang Wu, Yi-Zhuo Lu, Xue-Hua Chen, Bing-Ya Liu, Min-Hua Zheng, Jian-Chun Cai
Gastric cancer (GC) is one of the most common malignancies worldwide. The prognosis of GC is poor, mostly due to widespread metastasis. p21-activated kinase 1 (Pak1), the best characterized member of an evolutionarily conserved family of serine/threonine kinases, plays an important role in the regulation of cell morphogenesis, motility, mitosis and angiogenesis. By qRT-PCR and Gelatin zymograph assay, we demonstrated in the present study that stable overexpression of Pak1 induced matrix metalloproteinase (MMP)-2 mRNA expression and activity in the human MKN45 GC cell line...
May 16, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28534956/effects-of-octreotide-on-hepatic-glycogenesis-in-rats-with-high-fat-diet%C3%A2-induced-obesity
#11
Xiao-Xia Wang, Ting Ye, Mao Li, Xian Li, Ou Qiang, Cheng-Wei Tang, Rui Liu
Reduced hepatic glycogenesis is one of the most important causes of metabolic abnormalities in non‑alcoholic fatty liver disease. Octreotide, a somatostatin analogue, has been demonstrated to promote weight loss and improve metabolic disorders in mice with high fat diet (HFD)‑induced obesity. However, whether octreotide affects hepatic glycogenesis is unknown. The aim of the present study was to verify the effects of octreotide on hepatic glycogenesis in rats with HFD‑induced obesity. Male Sprague‑Dawley rats were fed a standard diet or a HFD for 24 weeks...
May 16, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28534863/the-clinical-course-of-patients-with-preschool-manifestation-of-type-1-diabetes-is-independent-of-the-hla-dr-dq-genotype
#12
Christina Reinauer, Joachim Rosenbauer, Christina Bächle, Christian Herder, Michael Roden, Sian Ellard, Elisa De Franco, Beate Karges, Reinhard W Holl, Jürgen Enczmann, Thomas Meissner
INTRODUCTION: Major histocompatibility complex class II genes are considered major genetic risk factors for autoimmune diabetes. We analysed Human Leukocyte Antigen (HLA) DR and DQ haplotypes in a cohort with early-onset (age < 5 years), long term type 1 diabetes (T1D) and explored their influence on clinical and laboratory parameters. METHODS: Intermediate resolution HLA-DRB1, DQA1 and DQB1 typing was performed in 233 samples from the German Paediatric Diabetes Biobank and compared with a local control cohort of 19,544 cases...
May 19, 2017: Genes
https://www.readbyqxmd.com/read/28534839/exploring-the-pivotal-role-of-the-ck2-hinge-region-sub-pocket-in-binding-with-tricyclic-quinolone-analogues-by-computational-analysis
#13
Yue Zhou, Na Zhang, Shan Tang, Xiaoqian Qi, Lijiao Zhao, Rugang Zhong, Yongzhen Peng
Protein kinase CK2 has been considered as an attractive therapeutic target of cancer therapy. The tricyclic quinoline compound CX-4945 is the first representative of CK2 inhibitors used in human clinical trials. The binding of non-2,6-naphtyridine substituted compounds 27e (IC50 > 500 nM) and 27h (IC50 > 1000 nM) to CK2 is abolished. However, the unbinding mechanisms due to the key pharmacophore group replacement of compounds 27e and 27h are unveiled. In the present work, combined computational analysis was performed to investigate the underlying structural basis of the low-affinity of two systems...
May 19, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28534825/a-novel-combination-of-withaferin-a-and-sulforaphane-inhibits-epigenetic-machinery-cellular-viability-and-induces-apoptosis-of-breast-cancer-cells
#14
Kendra J Royston, Neha Udayakumar, Kayla Lewis, Trygve O Tollefsbol
With cancer often classified as a disease that has an important epigenetic component, natural compounds that have the ability to regulate the epigenome become ideal candidates for study. Humans have a complex diet, which illustrates the need to elucidate the mechanisms of interaction between these bioactive compounds in combination. The natural compounds withaferin A (WA), from the Indian winter cherry, and sulforaphane (SFN), from cruciferous vegetables, have numerous anti-cancer effects and some report their ability to regulate epigenetic processes...
May 19, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28534824/isorhynchophylline-a-potent-plant-alkaloid-induces-apoptotic-and-anti-metastatic-effects-in-human-hepatocellular-carcinoma-cells-through-the-modulation-of-diverse-cell-signaling-cascades
#15
Hanwool Lee, Seung Ho Baek, Jong Hyun Lee, Chulwon Kim, Jeong-Hyeon Ko, Seok-Geun Lee, Arunachalam Chinnathambi, Sulaiman Ali Alharbi, Woong Mo Yang, Jae-Young Um, Gautam Sethi, Kwang Seok Ahn
Isorhynchophylline (Rhy) is an active pharmacological component of Uncaria rhynchophylla that has been reported previously to exert significant antihypertensive and neuroprotective effects. However, very little is known about its potential anti-cancer activities. This study was carried out to evaluate the anticancer effects of Rhy against various human carcinoma cell lines. We found that Rhy exhibited substantial cytotoxic effect against human hepatocellular carcinoma HepG2 cells when compared with other human carcinoma cell lines including those of lung, pancreas, prostate, head and neck, breast, multiple myeloma, brain and renal cell carcinoma...
May 19, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28534787/effect-of-waveform-on-tactile-perception-by-electrovibration-displayed-on-touch-screens
#16
Yasemin Vardar, Burak Guclu, Cagatay Basdogan
In this study, we investigated the effect of input voltage waveform on our haptic perception of electrovibration on touch screens. Through psychophysical experiments performed with eight subjects, we first measured the detection thresholds of electrovibration stimuli generated by sinusoidal and square voltages at various fundamental frequencies. We observed that the subjects were more sensitive to stimuli generated by square wave voltage than sinusoidal one for frequencies lower than 60 Hz. Using Matlab simulations, we showed that the sensation difference of waveforms in low fundamental frequencies occurred due to the frequency-dependent electrical properties of human skin and human tactile sensitivity...
May 16, 2017: IEEE Transactions on Haptics
https://www.readbyqxmd.com/read/28534720/spatial-and-visual-reasoning-do-these-abilities-improve-in-first-year-veterinary-medical-students-exposed-to-an-integrated-curriculum
#17
J Claudio Gutierrez, Munashe Chigerwe, Jan E Ilkiw, Patricia Youngblood, Steven D Holladay, Sakti Srivastava
Spatial visualization ability refers to the human cognitive ability to form, retrieve, and manipulate mental models of spatial nature. Visual reasoning ability has been linked to spatial ability. There is currently limited information about how entry-level spatial and visual reasoning abilities may predict veterinary anatomy performance or may be enhanced with progression through the veterinary anatomy content in an integrated curriculum. The present study made use of two tests that measure spatial ability, and one test that measures visual reasoning ability in veterinary students: Guay's Visualization of Views Test, adapted version (GVVT), the Mental Rotations Test (MRT), and Raven's Advanced Progressive Matrices Test, short form (RavenT)...
May 23, 2017: Journal of Veterinary Medical Education
https://www.readbyqxmd.com/read/28534661/characterization-of-human-fetal-brain-endothelial-cells-reveals-barrier-properties-suitable-for-in%C3%A2-vitro-modeling-of-the-bbb-with-syngenic-co-cultures
#18
Allison M Andrews, Evan M Lutton, Lee A Cannella, Nancy Reichenbach, Roshanak Razmpour, Matthew J Seasock, Steven J Kaspin, Steven F Merkel, Dianne Langford, Yuri Persidsky, Servio H Ramirez
Endothelial cells (ECs) form the basis of the blood-brain barrier (BBB), a physical barrier that selectively restricts transport into the brain. In vitro models can provide significant insight into BBB physiology, mechanisms of human disease pathology, toxicology, and drug delivery. Given the limited availability of primary human adult brain microvascular ECs ( aBMVECs), human fetal tissue offers a plausible alternative source for multiple donors and the opportunity to build syngenic tri-cultures from the same host...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28534645/the-mitochondria-targeting-peptide-elamipretide-diminishes-circulating-htra2-in-st-segment-elevation-myocardial-infarction
#19
Marcus Hortmann, Samuel Robinson, Moritz Mohr, Maximillian Mauler, Daniela Stallmann, Jochen Reinöhl, Daniel Duerschmied, Karlheinz Peter, James Carr, C Michael Gibson, Christoph Bode, Ingo Ahrens
BACKGROUND: The extent of myocardial damage in patients with ST-segment elevation myocardial infarction (STEMI) depends on both the time to reperfusion as well as injury induced by ischaemia-reperfusion resulting in a cascade of cellular and humoral reactions. As a consequence of ischaemia-reperfusion in the heart, the high-temperature requirement serine peptidase 2 (HtrA2) is translocated from the mitochondria to the cytosol, whereupon it induces protease activity-dependent apoptosis mediated via caspases...
May 1, 2017: European Heart Journal. Acute Cardiovascular Care
https://www.readbyqxmd.com/read/28534193/antagonist-perturbation-mechanism-for-activation-function-2-fixed-motifs-active-conformation-and-docking-mode-of-retinoid-x-receptor-antagonists
#20
Motonori Tsuji
HX531, which contains a dibenzodiazepine skeleton, is one of the first retinoid X receptor (RXR) antagonists. Functioning via RXR-PPARγ heterodimer, this compound is receiving a lot of attention as a therapeutic drug candidate for diabetic disease controlling differentiation of adipose tissue. However, the active conformation of HX531 for RXRs is not well established. In the present study, quantum mechanics calculations and molecular mechanical docking simulations were carried out to precisely study the docking mode of HX531 with the human RXRα ligand-binding domain, as well as to provide a new approach to drug design using a structure-based perspective...
May 22, 2017: Journal of Computer-aided Molecular Design
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