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https://www.readbyqxmd.com/read/28429257/low-molecular-weight-components-of-the-metabolome-control-the-proliferative-activity-in-cellular-and-bacterial-cultures
#1
T Ya Vakhitov, N I Chalisova, S I Sitkin, T S Sall, O N Shalaeva, E V Demyanova, A S Morugina, A F Vinogradova, A V Petrov, A D Nozdrachev
The effects of blood metabolites and model cell culture exometabolites found in the human and animal blood metabolomes have been assessed. Specifically, the influence of carboxylic acids that are structural analogues of amino acids and the drug Aktoflor-C have been studied. Methods of organotypic culturing of rat tissues and Escherichia coli bacterial culturing have been used. It has been found that all the tested compounds either stimulate or inhibit cell proliferation in tissue cultures and proliferation in bacterial cultures...
January 2017: Doklady Biological Sciences: Proceedings of the Academy of Sciences of the USSR, Biological Sciences Sections
https://www.readbyqxmd.com/read/28427767/%C3%AE-arrestins-negatively-control-human-adrenomedullin-type-1-receptor-internalization
#2
Kenji Kuwasako, Kazuo Kitamura, Sayaka Nagata, Toshio Sekiguchi, Jiang Danfeng, Manabu Murakami, Yuichi Hattori, Johji Kato
Adrenomedullin (AM) is a potent hypotensive peptide that exerts a powerful variety of protective effects against multiorgan damage through the AM type 1 receptor (AM1 receptor), which consists of the calcitonin receptor-like receptor (CLR) and receptor activity-modifying protein 2 (RAMP2). Two β-arrestin (β-arr) isoforms, β-arr-1 and β-arr-2, play a central role in the agonist-induced internalization of many receptors for receptor resensitization. Notably, β-arr-biased agonists are now being tested in phase II clinical trials, targeting acute pain and acute heart failure...
April 17, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28425934/evaluation-of-the-effects-of-airborne-particulate-matter-on-bone-marrow-mesenchymal-stem-cells-bm-mscs-cellular-molecular-and-systems-biological-approaches
#3
Muhammad Abu-Elmagd, Mansour A Alghamdi, Magdy Shamy, Mamdouh I Khoder, Max Costa, Mourad Assidi, Roaa Kadam, Haneen Alsehli, Mamdooh Gari, Peter Natesan Pushparaj, Gauthaman Kalamegam, Mohammed H Al-Qahtani
Particulate matter (PM) contains heavy metals that affect various cellular functions and gene expression associated with a range of acute and chronic diseases in humans. However, the specific effects they exert on the stem cells remain unclear. Here, we report the effects of PM collected from the city of Jeddah on proliferation, cell death, related gene expression and systems of biological analysis in bone marrow mesenchymal stem cells (BM-MSCs), with the aim of understanding the underlying mechanisms. PM2...
April 20, 2017: International Journal of Environmental Research and Public Health
https://www.readbyqxmd.com/read/28420336/reduced-changes-in-protein-compared-to-mrna-levels-across-non-proliferating-tissues
#4
Kobi Perl, Kathy Ushakov, Yair Pozniak, Ofer Yizhar-Barnea, Yoni Bhonker, Shaked Shivatzki, Tamar Geiger, Karen B Avraham, Ron Shamir
BACKGROUND: The quantitative relations between RNA and protein are fundamental to biology and are still not fully understood. Across taxa, it was demonstrated that the protein-to-mRNA ratio in steady state varies in a direction that lessens the change in protein levels as a result of changes in the transcript abundance. Evidence for this behavior in tissues is sparse. We tested this phenomenon in new data that we produced for the mouse auditory system, and in previously published tissue datasets...
April 18, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28419419/the-isoprenoid-derivative-n6-benzyladenosine-cm223-exerts-antitumor-effect-in-glioma-patient-derived-primary-cells-through-the-mevalonate-pathway
#5
Elena Ciaglia, Manuela Grimaldi, Mario Abate, Mario Scrima, Manuela Rodriquez, Chiara Laezza, Roberta Ranieri, Simona Pisanti, Pierangela Ciuffreda, Clementina Manera, Patrizia Gazzerro, Anna Maria D'Ursi, Maurizio Bifulco
BACKGROUND AND PURPOSE: N6-Isopentenyladenosine (i6A) is a modified nucleoside exerting in vitro and in vivo antiproliferative effects. We previously demonstrated that the i6A action is correlated to farnesyl pyrophosphate synthase (FPPS) expression and activity, a key enzyme involved in the mevalonate (MVA) pathway, which is found aberrant in brain cancer. To develop new anti-glioma strategies, we looked for other valuable compounds exhibiting improved activity as compared to i6A. EXPERIMENTAL APPROACH: we designed and synthesized i6A derivatives characterized by the introduction of diverse chemical moieties in the N6 position of adenosine and tested for their efficacy in U87 and primary derived patient's glioma cell model...
April 18, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28419410/selective-and-state-dependent-activation-of-tresk-background-potassium-channel-by-cloxyquin
#6
Miklós Lengyel, Alice Dobolyi, Gábor Czirják, Péter Enyedi
BACKGROUND AND PURPOSE: Cloxyquin (5-cloroquinolin-8-ol) has been previously described as an activator of TRESK (K2P 18.1, TWIK-related spinal cord K(+) channel) background potassium channel. We have examined the specificity of the drug by testing several K2P channels. We have investigated the mechanism of cloxyquin-mediated TRESK activation, focusing on the differences between the physiologically relevant regulatory states of the channel. EXPERIMENTAL APPROACH: Potassium currents were measured by two-electrode voltage clamp in Xenopus oocytes and by whole-cell patch clamp in mouse dorsal root ganglion (DRG) neurons...
April 18, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28418172/analgesic-effect-of-clobazam-in-chronic-low-back-pain-but-not-in-experimentally-induced-pain
#7
J Schliessbach, P H Vuilleumier, A Siegenthaler, L Bütikofer, A Limacher, P Juni, H U Zeilhofer, L Arendt-Nielsen, M Curatolo
BACKGROUND: Chronic pain is frequently associated with hypersensitivity of the nervous system, and drugs that increase central inhibition are therefore a potentially effective treatment. Benzodiazepines are potent modulators of GABAergic neurotransmission and are known to exert antihyperalgesic effects in rodents, but translation into patients are lacking. This study investigates the effect of the benzodiazepine clobazam in chronic low-back pain in humans. The aim of this study is to explore the effect of GABA modulation on chronic low-back pain and on quantitative sensory tests...
April 18, 2017: European Journal of Pain: EJP
https://www.readbyqxmd.com/read/28417283/bis-anthracycline-wp760-abrogates-melanoma-cell-growth-by-transcription-inhibition-p53-activation-and-igf1r-downregulation
#8
Magdalena Olbryt, Aleksandra Rusin, Izabela Fokt, Anna Habryka, Patrycja Tudrej, Sebastian Student, Aleksander Sochanik, Rafał Zieliński, Waldemar Priebe
Anthracycline chemotherapeutics, e.g. doxorubicin and daunorubicin, are active against a broad spectrum of cancers. Their cytotoxicity is mainly attributed to DNA intercalation, interference with topoisomerase activity, and induction of double-stranded DNA breaks. Since modification of anthracyclines can profoundly affect their pharmacological properties we attempted to elucidate the mechanism of action, and identify possible molecular targets, of bis-anthracycline WP760 which previously demonstrated anti-melanoma activity at low nanomolar concentrations...
April 17, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28415690/identification-of-dna-pkcs-as-a-primary-resistance-factor-of-tic10-in-hepatocellular-carcinoma-cells
#9
Long Cheng, Yuan-Yuan Liu, Pei-Hua Lu, Yi Peng, Qiang Yuan, Xin-Shi Gu, Yong Jin, Min-Bin Chen, Xu-Ming Bai
The current study tested the anti-hepatocellular carcinoma (HCC) cell activity of TIC10, a first-in-class small-molecule tumor necrosis (TNF)-related apoptosis-inducing ligand (TRAIL) inducer. TIC10 exerted potent anti-proliferative and pro-apoptotic actions in primary and established human HCC cells. TIC10 blocked Akt-Erk activation, leading to Foxo3a nuclear translocation, as well as TRAIL and death receptor-5 (DR5) transcription in HCC cells. We propose that DNA-PKcs is a major resistance factor of TIC10 possibly via inhibiting Foxo3a nuclear translocation...
March 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28409183/combination-of-il-10-and-il-2-induces-oligoclonal-human-cd4-t-cell-expansion-during-xenogeneic-and-allogeneic-gvhd-in-humanized-mice
#10
Sojan Abraham, Hua Guo, Jang-Gi Choi, Chunting Ye, Midhun Ben Thomas, Nora Ortega, Alok Dwivedi, N Manjunath, Guohua Yi, Premlata Shankar
IL-10 is a crucial anti-inflammatory cytokine which can also exert a seemingly divergent immunostimulatory effects under certain conditions. We found high levels of the cytokine in a xenogeneic GVHD model where NOD-scid IL2rγcnull (NSG) mice were transplanted with human PBMCs in presence of IL-2. Presence of exogenous IL-10 altered the kinetics of IL-2 induced human T cell reconstitution in vivo, showing an initial delay, followed by rapid expansion. Further, compared to IL-2 alone, treatment with IL-2 in combination with IL-10 increased survival in most animals and completely protected ∼20% of mice from GVHD...
April 2017: Heliyon
https://www.readbyqxmd.com/read/28400719/reduction-of-huntington-s-disease-rna-foci-by-cag-repeat-targeting-reagents
#11
Martyna O Urbanek, Agnieszka Fiszer, Wlodzimierz J Krzyzosiak
In several human polyglutamine diseases caused by expansions of CAG repeats in the coding sequence of single genes, mutant transcripts are detained in nuclear RNA foci. In polyglutamine disorders, unlike other repeat-associated diseases, both RNA and proteins exert pathogenic effects; therefore, decreases of both RNA and protein toxicity need to be addressed in proposed treatments. A variety of oligonucleotide-based therapeutic approaches have been developed for polyglutamine diseases, but concomitant assays for RNA foci reduction are lacking...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28397820/bitter-taste-receptor-agonists-mitigate-features-of-allergic-asthma-in-mice
#12
Pawan Sharma, Roslyn Yi, Ajay P Nayak, Nadan Wang, Francesca Tang, Morgan J Knight, Shi Pan, Brian Oliver, Deepak A Deshpande
Asthma is characterized by airway inflammation, mucus secretion, remodeling and hyperresponsiveness (AHR). Recent research has established the bronchodilatory effect of bitter taste receptor (TAS2R) agonists in various models. Comprehensive pre-clinical studies aimed at establishing effectiveness of TAS2R agonists in disease models are lacking. Here we aimed to determine the effect of TAS2R agonists on features of asthma. Further, we elucidated a mechanism by which TAS2R agonists mitigate features of asthma...
April 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28396425/unusual-active-site-location-and-catalytic-apparatus-in-a-glycoside-hydrolase-family
#13
Jose Munoz-Munoz, Alan Cartmell, Nicolas Terrapon, Bernard Henrissat, Harry J Gilbert
The human gut microbiota use complex carbohydrates as major nutrients. The requirement for an efficient glycan degrading systems exerts a major selection pressure on this microbial community. Thus, we propose that these bacteria represent a substantial resource for discovering novel carbohydrate active enzymes. To test this hypothesis, we focused on enzymes that hydrolyze rhamnosidic bonds, as cleavage of these linkages is chemically challenging and there is a paucity of information on l-rhamnosidases. Here we screened the activity of enzymes derived from the human gut microbiota bacterium Bacteroides thetaiotaomicron, which are up-regulated in response to rhamnose-containing glycans...
April 10, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28395350/variability-in-heat-strain-in-fully-encapsulated-impermeable-suits-in-different-climates-and-at-different-work-loads
#14
Emiel A DenHartog, Candace D Rubenstein, A Shawn Deaton, Cornelis Peter Bogerd
A major concern for responders to hazardous materials (HazMat) incidents is the heat strain that is caused by fully encapsulated impermeable (NFPA 1991) suits. In a research project, funded by the US Department of Defense, the thermal strain experienced when wearing these suits was studied. Forty human subjects between the ages of 25 and 50 participated in a protocol approved by the local ethical committee. Six different fully encapsulated impermeable HazMat suits were evaluated in three climates: moderate (24°C, 50% RH, 20°C WBGT), warm-wet (32°C, 60% RH, 30°C WBGT), and hot-dry (45°C, 20% RH, 37°C WBGT, 200 W m-2 radiant load) and at three walking speeds: 2...
March 1, 2017: Annals of Work Exposures and Health
https://www.readbyqxmd.com/read/28391461/toxicological-assessment-of-tungsten-oxide-nanoparticles-in-rats-after-acute-oral-exposure
#15
Srinivas Chinde, Naresh Dumala, Mohammed Fazlur Rahman, Sarika Srinivas Kalyan Kamal, Srinivas Indu Kumari, Mohammed Mahboob, Paramjit Grover
Advances in and the rapid growth of the nanotechnology sector have escalated manufacture of nanoparticles (NPs), resulting in a significant increase in the probability of exposure of humans and wildlife to these materials. Many NPs have been found to exert genotoxicity. Therefore, genotoxicity studies are mandatory to assess the toxicity of NPs as a concern of succumbing to genetic diseases and cancers are universal. Tungsten oxide (WO3) NPs are being explored extensively in various fields. However, the toxicological data of WO3 NPs by oral route in mammals is limited...
April 8, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/28382744/exercise-and-bdnf-reduce-a%C3%AE-production-by-enhancing-%C3%AE-secretase-processing-of-app
#16
Saket M Nigam, Shaohua Xu, Joanna S Kritikou, Krisztina Marosi, Lennart Brodin, Mark P Mattson
Alzheimer's disease (AD) is an age-related neurodegenerative disorder characterized by aggregation of toxic forms of amyloid β peptide (Aβ). Treatment strategies have largely been focused on inhibiting the enzymes (β- and γ-secretases) that liberate Aβ from the amyloid precursor protein (APP). While evidence suggests that individuals who exercise regularly are at reduced risk for AD and studies of animal models demonstrate that running can ameliorate brain Aβ pathology and associated cognitive deficits, the underlying mechanisms are unknown...
April 6, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28377722/curcumin-improves-palmitate-induced-insulin-resistance-in-human-umbilical-vein-endothelial-cells-by-maintaining-proteostasis-in-endoplasmic-reticulum
#17
Mao Ye, Hong Qiu, Yingkang Cao, Min Zhang, Yan Mi, Jing Yu, Changhua Wang
Dysfunction of proteasome and autophagy will result in disturbance of endoplasmic reticulum (ER) proteostasis, and thus lead to long-term and chronic ER stress and subsequent unfolded protein response (UPR), which is implicated in the occurrence and development of insulin resistance. Curcumin exerts beneficial metabolic effects in in vitro cells and in vivo animal models of diabetes and diabetic complications including cardiovascular diseases, due to its powerful anti-oxidative and anti-inflammatory properties...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28374670/the-effect-of-ibuprofen-on-cytokine-production-by-mononuclear-cells-from-schizophrenic-patients
#18
H Bessler, D Cohen-Terica, M Djaldetti, P Sirota
The existence of a restrained inflammatory state in schizophrenic individuals posed the question whether anti-inflammatory drugs may exert antipsychotic effects. Therefore, the effect of ibuprofen (IB) on cytokine production by human peripheral blood mononuclear cells (PBMC) from schizophrenic patients was examined and compared to that of healthy subjects. PBMC from 25 schizophrenic patients and 24 healthy volunteers were incubated for 24 h with lipopolysaccharide (LPS) in the absence or presence of various concentrations of IB...
2017: Folia Biologica (Praha)
https://www.readbyqxmd.com/read/28373651/fatigue-modulates-dopamine-availability-and-promotes-flexible-choice-reversals-during-decision-making
#19
Pierpaolo Iodice, Claudio Ferrante, Luigi Brunetti, Simona Cabib, Feliciano Protasi, Mark E Walton, Giovanni Pezzulo
During decisions, animals balance goal achievement and effort management. Despite physical exercise and fatigue significantly affecting the levels of effort that an animal exerts to obtain a reward, their role in effort-based choice and the underlying neurochemistry are incompletely known. In particular, it is unclear whether fatigue influences decision (cost-benefit) strategies flexibly or only post-decision action execution and learning. To answer this question, we trained mice on a T-maze task in which they chose between a high-cost, high-reward arm (HR), which included a barrier, and a low-cost, low-reward arm (LR), with no barrier...
April 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28373109/modelling-the-bronchial-barrier-in-pulmonary-drug-delivery-a-human-bronchial-epithelial-cell-line-supplemented-with-human-tracheal-mucus
#20
Xabi Murgia, Hanzey Yasar, Cristiane Carvalho-Wodarz, Brigitta Loretz, Sarah Gordon, Konrad Schwarzkopf, Ulrich Schaefer, Claus-Michael Lehr
The airway epithelium together with the mucus layer coating it forms a protective system that efficiently filters and removes potentially harmful particles contained in inhaled air. The same mechanism, however, serves to entrap particulate drug carriers, precluding their interaction with their target. The mucus barrier is often neglected in in vitro testing setups employed for the assessment of pulmonary drug delivery strategies. Therefore, our aim was to more accurately model the bronchial barrier, by developing an in vitro system comprising a tight epithelial cell layer which may be optionally supplemented with a layer of human tracheal mucus...
April 1, 2017: European Journal of Pharmaceutics and Biopharmaceutics
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