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https://www.readbyqxmd.com/read/27911011/fragment-based-design-synthesis-and-biological-evaluation-of-1-substituted-indole-2-carboxylic-acids-as-selective-mcl-1-inhibitors
#1
Ziqian Wang, Wenjie Xu, Ting Song, Zongwei Guo, Lu Liu, Yudan Fan, Anhui Wang, Zhichao Zhang
Based on a known selective Mcl-1 inhibitor, 6-chloro-3-(3-(4-chloro-3,5-dimethylphenoxy)propyl)-1H-indole-2-carboxylic acid, we applied a fragment-based approach to obtain new molecules that extended into the p1 pocket of the BH3 groove and then exhibited binding selectivity for the Mcl-1 over the Bcl-2 protein. After we deconstructed the 1H-indole-2-carboxylic acid from the parental molecule, a benzenesulfonyl was substituted at the 1-position to adopt a geometry preferred for accessing the p1 pocket according to the binding mode of the parental molecule identified by X-ray crystallography...
December 2, 2016: Archiv der Pharmazie
https://www.readbyqxmd.com/read/27910476/operation-results-of-the-kstar-far-infrared-interferometer
#2
June-Woo Juhn, K C Lee, H M Wi, Y S Kim, Y U Nam
The 2015 KSTAR experimental campaign was the first year of routine measurement with a far infrared interferometer (FIRI) utilizing 118.87 μm CH3OH lasers at maximum 200 mW CW beam power. By using rtEFIT reconstruction, the path lengths of interferometers can be calculated and so the line-averaged electron densities n¯e from the FIRI and a millimeter-wave interferometer were in excellent agreement. In this way, the number of successfully diagnosed discharges is counted: 1003 shots or 83.7% of sustained discharges, defined as shots of plasma current IP ≥ 0...
November 2016: Review of Scientific Instruments
https://www.readbyqxmd.com/read/27909720/tetrandrine-inhibits-glioma-stem-like-cells-by-repressing-%C3%AE-catenin-expression
#3
Yong Zhang, Yu-Lin Wen, Ji-Wei Ma, Jie-Cheng Ye, Xiao Wang, Jian-Xian Huang, Chao-Yue Meng, Xiao-Ze Xu, Shao-Xiang Wang, Xue-Yun Zhong
Cancer stem cells (CSCs) in glioma are often responsible for relapse and resistance to therapy. The purpose of the present study was to confirm the self-renewal and migration inhibitory effects of tetrandrine (Tet), which is a compound extracted from the dried root of Stephania tetrandra S. Moore, toward glioma stem-like cells (GSLCs) and to examine the associated molecular mechanisms. Using a neurosphere culture technique, we enriched the GSLC population from the human glioblastoma cell lines U87 and U251...
November 23, 2016: International Journal of Oncology
https://www.readbyqxmd.com/read/27908125/a-h%C3%A3-ckel-source-sink-potential-theory-of-pauli-spin-blockade-in-molecular-electronic-devices
#4
Barry T Pickup, Patrick W Fowler, Irene Sciriha
This paper shows how to include Pauli (exclusion principle) effects within a treatment of ballistic molecular conduction that uses the tight-binding Hückel Hamiltonian and the source-sink-potential (SSP) method. We take into account the many-electron ground-state of the molecule and show that we can discuss ballistic conduction for a specific molecular device in terms of four structural polynomials. In the standard one-electron picture, these are characteristic polynomials of vertex-deleted graphs, with spectral representations in terms of molecular-orbital eigenvectors and eigenvalues...
November 28, 2016: Journal of Chemical Physics
https://www.readbyqxmd.com/read/27907201/tumor-necrosis-factor-like-weak-inducer-of-apoptosis-promotes-hepatic-stellate-cells-migration-via-canonical-nf-%C3%AE%C2%BAb-mmp9-pathway
#5
Mingcui Xu, Feng Zhang, Aixiu Wang, Chen Wang, Yu Cao, Ming Zhang, Mingming Zhang, Min Su, Xiaoping Zou, Guifang Xu, Yuzheng Zhuge
In the liver, the signal and function of tumor necrosis factor-like weak inducer of apoptosis (TWEAK) have mainly been assessed in association with liver regeneration. However, the effects of TWEAK on liver fibrosis have not been fully elucidated. To investigate the effects of TWEAK on human hepatic stellate cells (HSCs) and to explore the relevant potential mechanisms, human HSCs line-LX-2 were cultured with TWEAK. Cell migration was detected by transwell assay; cell viability was evaluated by Cell Counting Kit-8; the expression of MMP1, MMP2, MMP3, MMP7, MMP8, MMP9, MMP10, MMP11, MMP12, MMP13 gene was identified by quantitative real-time polymerase chain reaction and western blotting; the activity of matrix metalloproteinases (MMPs) was tested by enzyme-linked immuno sorbent assay; small interfering RNA transfection was applied for depletion of MMP9 and p65...
2016: PloS One
https://www.readbyqxmd.com/read/27907140/detection-of-acute-radiation-sickness-a-feasibility-study-in-non-human-primates-circulating-mirnas-for-triage-in-radiological-events
#6
Naresh Menon, Claude J Rogers, Agnes I Lukaszewicz, James Axtelle, Marshleen Yadav, Feifei Song, Arnab Chakravarti, Naduparambil K Jacob
Development of biomarkers capable of estimating absorbed dose is critical for effective triage of affected individuals after radiological events. Levels of cell-free circulating miRNAs in plasma were compared for dose-response analysis in non-human primates (NHP) exposed to lethal (6.5 Gy) and sub-lethal (1 and 3 Gy) doses over a 7 day period. The doses and test time points were selected to mimic triage needs in the event of a mass casualty radiological event. Changes in miRNA abundance in irradiated animals were compared to a non-irradiated cohort and a cohort experiencing acute inflammation response from exposure to lipopolysaccharide (LPS)...
2016: PloS One
https://www.readbyqxmd.com/read/27904738/recent-developments-in-the-management-of-invasive-fungal-infections-in-patients-with-oncohematological-diseases
#7
REVIEW
Markus Ruhnke, Stefan Schwartz
Patients with hematological cancer have a high risk of invasive fungal diseases (IFDs). These infections are mostly life threatening and an early diagnosis and initiation of appropriate antifungal therapy are essential for the clinical outcome. Most commonly, Aspergillus and Candida species are involved. However, other non-Aspergillus molds are increasingly be identified in cases of documented IFDs. Important risk factors are long lasting granulocytopenia with neutrophil counts below 500/μl for more than 10 days or graft-versus-host disease resulting from allogeneic stem-cell transplantation...
December 2016: Therapeutic Advances in Hematology
https://www.readbyqxmd.com/read/27904712/hyperbaric-oxygen-protects-mandibular-condylar-chondrocytes-from-interleukin-1%C3%AE-induced-apoptosis-via-the-pi3k-akt-signaling-pathway
#8
Hang Chen, Gaoyi Wu, Qi Sun, Yabing Dong, Huaqiang Zhao
Objectives: Mandibular condylar chondrocyte apoptosis is mainly responsible for the development and progression of temporomandibular joint osteoarthritis (TMJ-OA). Interleukin-1β (IL-1β) generally serves an agent that induces chondrocyte apoptosis. Hyperbaric oxygen (HBO) treatment increases proteoglycan synthesis in vivo. We explore the protective effect of HBO on IL-1β-induced mandibular condylar chondrocyte apoptosis in rats and the potential molecular mechanisms. Methods: Chondrocytes were isolated from the TMJ of 3-4-week old Sprague-Dawley rats...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27904706/the-central-role-of-hotair-in-the-malignancy-of-cd44-human-hypopharyngeal-carcinoma-cells
#9
Hongxia Cheng, Xinhua Cui, Ying Guo, Lintao Gu, Yaning Wang, Qirong Wang, Hui Liang
Human hypopharyngeal carcinoma is one of the most common malignant tumors. CD44 could serve as a molecular marker to screen for cancer stem cells (CSCs) in hypopharyngeal cancer. The aim of this study was to identify the role of HOX transcript antisense RNA (HOTAIR) on cell proliferation and invasion in CD44+ FADU cells (human hypopharyngeal carcinoma cells). We also explored the underlying mechanism contributing to HOTAIR's observed effects. CD44+ FADU cells were sorted and purified by flow cytometry and infected with lentivirus stably expressing HOTAIR shRNA...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27904093/nonequilibrium-molecular-switching-of-chiral-helicene-oligomers-in-double-helix-formation
#10
Masanori Shigeno
 Molecular switching is the phenomenon in which a molecular structural change occurs reversibly in response to an external stimulus or energy. It plays an important role in biology, in which it is used for sensing environmental changes. In contrast to well-studied equilibrium molecular switching involving thermodynamically stable states, nonequilibrium molecular switching involving a metastable state is a notable chemical phenomenon and is the theme of this study. Sulfonamido- and aminomethylenehelicene oligomers show a reversible structural change from a double helix to a random coil in dilute solution...
2016: Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan
https://www.readbyqxmd.com/read/27901001/ultraviolet-a-enhances-cathepsin-l-expression-and-activity-via-jnk-pathway-in-human-dermal-fibroblasts
#11
Qing-Fang Xu, Yue Zheng, Jian Chen, Xin-Ya Xu, Zi-Jian Gong, Yun-Fen Huang, Chun Lu, Howard I Maibach, Wei Lai
BACKGROUND: Cathepsin L (CatL) is a cysteine protease with strong matrix degradation activity that contributes to photoaging. Mannose phosphate-independent sorting pathways mediate ultraviolet A (UVA)-induced alternate trafficking of CatL. Little is known about signaling pathways involved in the regulation of UVA-induced CatL expression and activity. This study aims to investigate whether a single UVA irradiation affects CatL expression and activity and whether mitogen-activated protein kinase (MAPK)/activator protein-1 (AP-1) pathway is involved in the regulation of UVA-induced CatL expression and activity in human dermal fibroblasts (HDFs)...
2016: Chinese Medical Journal
https://www.readbyqxmd.com/read/27900034/mir-520e-regulates-cell-proliferation-apoptosis-and-migration-in-breast-cancer
#12
Ming Yi, Minghua Li, Xia Long, Jing Ye, Junwei Cui, Wei Wei, Huijuan Wan, Meijun Yin, Shuying Gao, Zhengming Su, Fangting Zhang
Previous studies have indicated that the deregulation of microRNAs contributes to tumorigenesis. Misregulation of microRNA-520e (miR-520e) has been observed in various types of cancer. However, the expression profile and biological function of miR-520e in breast cancer remains largely unknown. The present study demonstrated that miR-520e expression was significantly increased in breast cancer tissues compared with adjacent non-cancerous breast tissues in 21 patients, as revealed by reverse transcription-quantitative polymerase chain reaction...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27899156/echinococcus-multilocularis-in-foxes-and-raccoon-dogs-an-increasing-concern-for-baltic-countries
#13
Guna Bagrade, Gunita Deksne, Zanda Ozoliņa, Samantha Jane Howlett, Maria Interisano, Adriano Casulli, Edoardo Pozio
BACKGROUND: In Europe, the life-cycle of Echinococcus multilocularis is predominantly sylvatic, involving red foxes (Vulpes vulpes) as the main definitive hosts and rodents such as muskrats and arvicolids as intermediate hosts. The parasite is the etiological agent of human alveolar echinococcosis, a malignant zoonotic disease caused by the accidental ingestion of eggs shed by definitive hosts in their faeces. The aims of this study were to investigate the prevalence of E. multilocularis in red foxes and raccoon dogs (Nyctereutes procyonoides) and to study the environmental factors favouring the perpetuation of the parasite in Latvia...
November 29, 2016: Parasites & Vectors
https://www.readbyqxmd.com/read/27898868/relationships-among-ensiling-nutritional-fermentative-microbiological-traits-and-contamination-in-corn-silages-addressed-with-partial-least-squares-regression
#14
A Gallo, D Bassi, R Esposito, M Moschini, P S Cocconcelli, F Masoero
The objective of this work was to reduce the predictor dimensionality and to develop a model able to forecast contamination in corn silages. A survey on 33 dairy farms was performed, and samples from core, lateral, and apical parts of the feed-out face of corn silage bunkers were analyzed for chemical, biological (digestible and indigestible NDF), fermentative (pH, ammonia nitrogen, lactic acid, VFA, and ethanol), and microbiological (yeasts and molds) traits. Corn silage samples were analyzed for cell and spore counts by adoption of a molecular DNA-based method...
October 2016: Journal of Animal Science
https://www.readbyqxmd.com/read/27895781/9-aaa-inhibits-growth-and-induces-apoptosis-in-human-melanoma-a375-and-rat-prostate-adenocarcinoma-at-2-and-mat-lylu-cell-lines-but-does-not-affect-the-growth-and-viability-of-normal-fibroblasts
#15
Włodzimierz Korohoda, Anna Hapek, Monika Pietrzak, Damian Ryszawy, Zbigniew Madeja
The present study found that, similarly to 5-fluorouracil, low concentrations (1-10 µM) of 9-aminoacridine (9-AAA) inhibited the growth of the two rat prostate cancer AT-2 and Mat-LyLu cell lines and the human melanoma A375 cell line. However, at the same concentrations, 9-AAA had no effect on the growth and apoptosis of normal human skin fibroblasts (HSFs). The differences between the cellular responses of the AT-2 and Mat-LyLu cell lines, which differ in malignancy, were found to be relatively small compared with the differences between normal HSFs and the cancer cell lines...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27893682/peritoneal-dialysis-related-peritonitis-due-to-halomonas-hamiltonii-a-first-case-report
#16
Se Hwan Yeo, Jae Hoon Kwak, Yeo Un Kim, Jin Suk Lee, Hyo Jin Kim, Kyoung Hwa Park, Jung Sook Lee, Gyoung Yim Ha, Jeong Ho Lee, Jun Yeop Lee, Kyung Don Yoo
INTRODUCTION: Halomonas hamiltonii is a Gram-negative, halophilic, motile, and nonspore-forming rod bacterium. Although most Halomonas sp. are commonly found in saline environments, it has rarely been implicated as a cause of human infection. Herein, the authors present a case report of continuous ambulatory peritoneal dialysis (CAPD)-related peritonitis attributed to H hamiltonii. CASE PRESENTATION: An 82-year-old male patient who had been receiving CAPD therapy presented to an emergency department with complaints of abdominal pain and cloudy dialysate that had persisted for 2 days...
November 2016: Medicine (Baltimore)
https://www.readbyqxmd.com/read/27892789/4-vinylcyclohexene-diepoxide-disrupts-sperm-characteristics-endocrine-balance-and-redox-status-in-testes-and-epididymis-of-rats
#17
Isaac A Adedara, Amos O Abolaji, Emmanuel O Ladipo, Ore J Fatunmibi, Ayodeji O Abajingin, Ebenezer O Farombi
OBJECTIVES: Exposure to 4-vinylcyclohexene diepoxide (VCD) was reported to induce testicular germ cell toxicity in rodents. However, there is paucity of information on the precise biochemical and molecular mechanisms of VCD-induced male reproductive toxicity. METHODOLOGY: This study investigated the influence of VCD on testicular and epidydimal functions following oral exposure of Wistar rats to VCD at 0, 100, 250 and 500 mg/kg for 28 consecutive days. RESULTS: Administration of VCD significantly decreased the body weight gain and organo-somatic indices of the testes and epididymis...
November 28, 2016: Redox Report: Communications in Free Radical Research
https://www.readbyqxmd.com/read/27891128/immune-imbalances-in-non-alcoholic-fatty-liver-disease-from-general-biomarkers-and-neutrophils-to-interleukin-17-axis-activation-and-new-therapeutic-targets
#18
REVIEW
Feliciano Chanana Paquissi
Non-alcoholic fatty liver disease (NAFLD) is an increasing problem worldwide and is associated with negative outcomes such as cirrhosis, hepatocellular carcinoma, insulin resistance, diabetes, and cardiovascular events. Current evidence shows that the immune response has an important participation driving the initiation, maintenance, and progression of the disease. So, various immune imbalances, from cellular to cytokines levels, have been studied, either for better compression of the disease pathophysiology or as biomarkers for severity assessment and outcome prediction...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27890084/comparison-of-molecular-and-conventional-methods-for-the-diagnosis-of-fasciola-hepatica-infection-in-the-field
#19
Maria Immaculata Arifin, Johan Höglund, Adam Novobilský
The liver fluke, Fasciola hepatica, is one of the major parasite threats to livestock industries world-wide. In sheep and cattle, F. hepatica infection is commonly diagnosed using a range of methods. Aside from conventional coprological and serological diagnostic methods, there are also several molecular methods available based on the detection of liver fluke DNA in faeces. In this study, the outcomes of faecal egg count (FEC), serology and coproantigen ELISA (cELISA) were compared with the performance of polymerase chain reaction (PCR) and loop-mediated isothermal amplification (LAMP) in diagnosis of F...
December 15, 2016: Veterinary Parasitology
https://www.readbyqxmd.com/read/27887693/reprint-of-survey-and-first-molecular-characterization-of-echinococcus-granulosus-sensu-stricto-g1-in-pampas-fox-lycalopex-gymnocercus-in-buenos-aires-province-argentina
#20
Nathalia Paula Scioscia, Romina Sandra Petrigh, Pablo Martín Beldomenico, Martín Fugassa, Guillermo María Denegri
Echinococcosis is a zoonosis caused by tapeworms of the genus Echinococcus. Echinococcus granulosus sensu lato (s. l.) has a world-wide distribution and its transmission is primarily maintained in a synanthropic cycle with dogs as definitive hosts and livestock species as intermediate hosts. However, many wild canids also function as definitive hosts for E. granulosus s. l. Echinococcosis in humans is mainly caused by E. granulosus sensu stricto (s. s.) G1 genotype. In the present work, we expanded the epidemiological study on echinococcosis reported cases in Pampas fox (Lycalopex gymnocercus) to provide a prevalence estimate for rural areas of southern Buenos Aires province, Argentina...
November 22, 2016: Acta Tropica
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