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Inhibitory control

Asmaa E Kassab, Ehab M Gedawy
As we are interested in synthetizing biologically active leads with dual anticancer and antibacterial activity, we adopted biology oriented drug synthesis (BIODS) strategy to synthesize a series of novel ciprofloxacin (CP) hybrids. The National Cancer Institute (USA) selected seventeen newly synthesized compounds for anticancer evaluation against 59 different human tumor cell lines. Five compounds 3e, 3f, 3h, 3o and 3p were further studied through determination of IC50 values against the most sensitive cancer cell lines...
March 9, 2018: European Journal of Medicinal Chemistry
Lisa Menegazzo, Valentina Scattolini, Roberta Cappellari, Benedetta Maria Bonora, Mattia Albiero, Mario Bortolozzi, Filippo Romanato, Giulio Ceolotto, Saula Vigili de Kreutzeberg, Angelo Avogaro, Gian Paolo Fadini
AIMS: Diabetes is associated with an excess release of neutrophil extracellular traps (NETs) and an enhanced NETosis, a neutrophil cell death programme instrumental to anti-microbial defences, but also involved in tissue damage. We herein investigated whether the antidiabetic drug metformin protects against NETosis. METHODS: We measured NET components in the plasma of patients with pre-diabetes who were randomized to receive metformin or placebo for 2 months. To control for the effect on glucose, we also measured NET components in the plasma of patients with type 2 diabetes before and after treatment with insulin or dapagliflozin...
March 15, 2018: Acta Diabetologica
Mikael Tiger, Katarina Varnäs, Yoshiro Okubo, Johan Lundberg
Major depressive disorder (MDD) is the leading cause of disability worldwide. The serotonin hypothesis may be the model of MDD pathophysiology with the most support. The majority of antidepressants enhance synaptic serotonin levels quickly, while it usually takes weeks to discern MDD treatment effect. It has been hypothesized that the time lag between serotonin increase and reduction of MDD symptoms is due to downregulation of inhibitory receptors such as the serotonin 1B receptor (5-HT1BR). The research on 5-HT1BR has previously been hampered by a lack of selective ligands for the receptor...
March 15, 2018: Psychopharmacology
Yaming Xi, Zhuanzhen Ma, Hao Zhang, Maowen Yuan, Lina Wang
The aim of the present study was to investigate the cytotoxic effect and multi-drug resistance (MDR) of Clostridium difficile toxin A (TcdA) on K562/A02 cells, and understand its underlying molecular pathways. K562/A02 cells were treated with TcdA at different concentrations for 24, 48 and 72 h, and the inhibition effect and drug resistance of TcdA on K562/A02 cell proliferation was assessed by methyl thiazolyl tetrazolium colorimetric assay. Furthermore, cell cycle-apoptosis was analyzed by flow cytometry, P-glycoprotein (P-gp) expression was determined by western blot analysis and caspase-3 activity was measured using a caspase-3 activity kit...
April 2018: Oncology Letters
Fabiola Trejo-Vazquez, Idalia Garza-Veloz, Gabriela Alejandra Villela-Ramirez, Yolanda Ortiz-Castro, Panfilo Mauricio-Saucedo, Edith Cardenas-Vargas, Mariana Diaz-Baez, Miguel A Cid-Baez, Rodrigo Castañeda-Miranda, Jose Manuel Ortiz-Rodriguez, Luis Octavio Solis-Sanchez, Margarita L Martinez-Fierro
Inflammatory bowel disease (IBD) includes ulcerative colitis (UC), Crohn's disease (CD) and indeterminate colitis. As these subtypes of IBD display important differences in the behavior of the natural course of the disease, the identification of non-invasive markers for IBD is important. The aim of the present study was to evaluate the serum levels of 10 adipokines and their association with endoscopic activity in IBD. The 10-protein profile (C-peptide, ghrelin, gastric inhibitory polypeptide, glucagon-like peptide-1, glucagon, insulin, leptin, plasminogen activator inhibitor-1, resistin and visfatin) was evaluated using serum from 53 participants (23 UC and 11 CD patients, as well as 19 controls) from Zacatecas (Mexico) by using the Bio-Plex Pro Human Diabetes 10-Plex Panel (Bio-Rad Laboratories, Inc...
April 2018: Experimental and Therapeutic Medicine
Oscar Illescas, Juan C Gomez-Verjan, Lizbeth García-Velázquez, Tzipe Govezensky, Miriam Rodriguez-Sosa
Human macrophage migration inhibitory factor (MIF) is a cytokine that plays a role in several metabolic and inflammatory processes. Single nucleotide polymorphism (SNP) -173 G/C (rs755622) on MIF gene has been associated with numerous diseases, such as arthritis and cancer. However, most of the reports concerning the association of MIF with these and other pathologies are inconsistent and remain quite controversial. Therefore, we performed a meta-analysis from 96 case-control studies on -173 G/C MIF SNP and stratified the data according to the subjects geographic localization or the disease pathophysiology, in order to determine a more meaningful significance to this SNP...
2018: Frontiers in Genetics
Rupesh K Chikara, Erik C Chang, Yi-Chen Lu, Dar-Shong Lin, Chin-Teng Lin, Li-Wei Ko
A reward or punishment can modulate motivation and emotions, which in turn affect cognitive processing. The present simultaneous functional magnetic resonance imaging-electroencephalography study examines neural mechanisms of response inhibition under the influence of a monetary reward or punishment by implementing a modified stop-signal task in a virtual battlefield scenario. The participants were instructed to play as snipers who open fire at a terrorist target but withhold shooting in the presence of a hostage...
2018: Frontiers in Human Neuroscience
Lei Wang, Liang Liu, Jing Wang, YueTong Chen
OBJECTIVE: The present study aimed to explore the inhibitory effect of artesunate on the growth and apoptosis of gastric cancer cells, in order to search for high effective and low toxic anti-gastric cancer drugs. METHODS: Flow cytometry was used to detect the CDC25A protein expression in different gastric diseases. After the treatment of different concentrations of artesunate (0, 30, 60, 120 μmol/l) on the gastric cancer cell line SGC-7901 cells for 24 h, 0 μmol/l Art was instead of normal saline as control group, the expression of CDC25A, Bcl-2, Bax, Caspase-3 protein, mitochondrial membrane potential, cell apoptosis and cell cycle were detected by flow cytometry...
March 12, 2018: Archives of Medical Research
Peyton W Weems, Michael N Lehman, Lique M Coolen, Robert L Goodman
Work over the last 15 years on the control of pulsatile LH secretion has focused largely on a set of neurons in the arcuate nucleus (ARC) that contains two stimulatory neuropeptides, critical for fertility in humans (kisspeptin and neurokinin B (NKB)) and the inhibitory endogenous opioid peptide (EOP), dynorphin, and are now known as KNDy (kisspeptin-NKB-dynorphin) neurons. In this review, we consider the role of each of the KNDy peptides in the generation of GnRH pulses and the negative feedback actions of ovarian steroids, with an emphasis on NKB and dynorphin...
2018: Vitamins and Hormones
Richard Lindqvist, Chaitanya Kurhade, Jonathan D Gilthorpe, Anna K Överby
BACKGROUND: Flaviviruses are a group of diverse and emerging arboviruses and an immense global health problem. A number of flaviviruses are neurotropic, causing severe encephalitis and even death. Type I interferons (IFNs) are the first line of defense of the innate immune system against flavivirus infection. IFNs elicit the concerted action of numerous interferon-stimulated genes (ISGs) to restrict both virus infection and replication. Viperin (virus-inhibitory protein, endoplasmic reticulum-associated, IFN-inducible) is an ISG with broad-spectrum antiviral activity against multiple flaviviruses in vitro...
March 15, 2018: Journal of Neuroinflammation
Sophie Mißbach, Denis Aleksic, Lisa Blaschke, Timm Hassemer, Kyung Jin Lee, Martin Mansfeld, Jana Hänske, Johannes Handler, Robert Kammerer
BACKGROUND: The CEA gene family is one of the most rapidly evolving gene families in the human genome. The founder gene of the family is thought to be an ancestor of the inhibitory immune checkpoint molecule CEACAM1. Comprehensive analyses of mammalian genomes showed that the CEA gene family is subject to tremendous gene family expansion and contraction events in different mammalian species. While in some species (e.g. rabbits) less than three CEACAM1 related genes exist, were in others (certain microbat species) up to 100 CEACAM1 paralogs identified...
March 15, 2018: BMC Evolutionary Biology
Corinna Schmitz, Heidi Noels, Omar El Bounkari, Eva Straussfeld, Remco T A Megens, Marieke Sternkopf, Setareh Alampour-Rajabi, Christine Krammer, Pathricia V Tilstam, Norbert Gerdes, Christina Bürger, Aphrodite Kapurniotu, Richard Bucala, Joachim Jankowski, Christian Weber, Jürgen Bernhagen
The inflammatory cytokine macrophage migration-inhibitory factor (MIF) promotes atherosclerosis via lesional monocyte and T-cell recruitment. B cells have emerged as important components in atherogenesis, but the interaction between MIF and B cells in atherogenesis is unknown. Here, we investigated the atherosclerotic phenotype of Mif-gene deletion in Apoe-/- mice. Apoe-/- Mif-/- mice on a Western-diet exhibited strongly reduced atherosclerotic lesions in brachiocephalic artery (BC) and abdominal aorta compared with controls...
March 15, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
H-H Brackmann, G C White, E Berntorp, T Andersen, C Escuriola-Ettingshausen
Development of inhibitory antibodies to infused factor VIII (FVIII) concentrates continues to be the most serious complication of haemophilia A management. Induction of immune tolerance by administering high doses of FVIII concentrate (antigen) and prothrombin complex concentrates to control bleeding was originated in the 1970s in Bonn, Germany, by Dr Hans-Hermann Brackmann, and became known as the Bonn protocol. ITI transformed the life of the index patient, who was 19 years of age when he began treatment, and dramatically improved the medical landscape for all patients with haemophilia and inhibitors...
April 2018: Haemophilia: the Official Journal of the World Federation of Hemophilia
Jie-Li Lv, Zhou Li, Li-Min Guo, Lai-Bin Zhang
Two new sesquiterpene lactones, artelavanolides A (1) and B (2), and four known sesquiterpene lactones (3-6) were isolated from the leaves of Artemisia lavandulaefolia. Their structures were elucidated based on the analysis of spectroscopic data (1D, 2D NMR and HRESIMS). The absolute configuration of 1 was determined by the analysis of single-crystal X-ray diffraction data. Artelavanolide A (1) is a rare sesquiterpene lactone possessing an unusual skeleton with the linkage of Me(14)-C(1) that is probably formed through a rearrangement of the guaiane-type sesquiterpenoids...
March 15, 2018: Chemistry & Biodiversity
Wen-Han Yu, Cormac Cosgrove, Christoph T Berger, Patrick C Cheney, Marina Krykbaeva, Arthur Y Kim, Lia Lewis-Ximenez, Georg M Lauer, Galit Alter
Background: Hepatitis B virus (HBV) affects up to 400 million people worldwide and accounts for approximately one million deaths per year from liver pathologies. Current treatment regimens are effective in suppressing viremia but usually have to be taken indefinitely, warranting research into new therapeutic approaches. Acute HBV infection in adults almost universally results in resolution of viremia, with the exception of immunocompromised persons, suggesting that the immune response can functionally cure or even eradicate HBV infection...
2018: Pathogens & Immunity
Chunqing Dou, Mingming Han, Bao Zhang, Liyuan Sun, Xin Jin, Tao Li
Previous studies have indicated that chrysotoxene may be a potential drug used to treat tumors, however the effect of chrysotoxene on hepatoblastoma remains unknown. Therefore, the present study aimed to investigate the cytotoxic effect and elucidate the potential molecular mechanism of chrysotoxene on human hepatoblastoma HepG2 cells. Chrysotoxene (5-40 µg/ml) exhibited cytotoxic activity against HepG2 cells with inhibitory rates of 24.67-84.06% (half maximal inhibitory concentration, 19.64 µg/ml), observed from a Cell Counting Kit-8 assay...
April 2018: Oncology Letters
Xiaoli Wang, Wei Xiong, Yiyin Tang
Breast cancer is one of the most common metastatic tumor types. Reports have suggested that Tunicamycin may inhibit the aggressiveness of cancer cells by promoting their apoptosis. In the present study, the inhibitory effects of Tunicamycin were investigated and the potential molecular mechanism underlying the Tunicamycin-inhibited growth and aggressiveness of breast cancer cells was explored. In vitro assays demonstrated that Tunicamycin significantly inhibited growth and arrested the cell cycle of breast cancer cells in a dose-dependent manner, compared with control cells...
April 2018: Oncology Letters
Arun Gupta, Pratima Murthy, Shobini Rao
Chronic use of mind altering substances can lead to a wide variety of neuropsychological deficits, affecting the domains of attention, learning, memory, reasoning. Executive functions such as working memory, cognitive flexibility and inhibitory control may specifically be impaired. These deficits can impact engagement in effective psychosocial interventions. Mild to moderate cognitive dysfunction may not be picked up in routine clinical examination or through commonly used tests like the mini-mental state examination (MMSE)...
February 2018: Indian Journal of Psychiatry
Laura Lopez-Sanz, Susana Bernal, Carlota Recio, Iolanda Lazaro, Ainhoa Oguiza, Ana Melgar, Luna Jimenez-Castilla, Jesus Egido, Carmen Gomez-Guerrero
Oxidative stress resulting from excessive production of reactive oxygen species (ROS) or impaired antioxidant defenses is closely related to the development of diabetic vascular complications, including nephropathy and atherosclerosis. Chronic activation of Janus kinase/Signal transducer and activator of transcription (JAK/STAT) signaling pathway contributes to diabetic complications by inducing expression of genes involved in cell proliferation, fibrosis, inflammation, and oxidative stress. Suppressors of cytokine signaling (SOCS) family of endogenous JAK/STAT regulators is an attractive target for therapeutic intervention...
March 14, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
Nathan Zuzow, Arit Ghosh, Marilyn Leonard, Jeffrey Liao, Bing Yang, Eric J Bennett
Previous genetic and biochemical studies from S. cerevisiae have identified a critical ribosome-associated quality control complex (RQC) that facilitates resolution of stalled ribosomal complexes. While components of the mammalian RQC have been examined in vitro , a systematic characterization of RQC protein interactions in mammalian cells has yet to be described. Here, we utilize both proximity-labeling proteomic approaches, BioID and APEX, and traditional affinity-based strategies to both identify interacting proteins of mammalian RQC members and putative substrates for the RQC resident E3 ligase, Ltn1...
March 14, 2018: Molecular Biology of the Cell
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