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https://www.readbyqxmd.com/read/28098912/microrna-9-limits-hepatic-fibrosis-by-suppressing-the-activation-and-proliferation-of-hepatic-stellate-cells-by-directly-targeting-mrp1-abcc1
#1
Jie Sun, Huanying Zhang, Liying Li, Lianfeng Yu, Lifang Fu
Liver fibrosis is a chronic liver disease characterized by the proliferation and activation of hepatic stellate cells (HSCs) and excessive deposition of extracellular matrix (ECM). Research suggests that microRNAs (miRNAs) are a new type of regulator of liver fibrosis. In the present study, we investigated the role of microRNA-9 (miR-9) in the process of liver fibrosis, as well as the underlying mechanism of action. Downregulated levels of miR-9 were found in fibrotic liver tissues and activated HSCs as detected by qRT-PCR; whereas, expression of multidrug resistance‑associated protein 1 (MRP1/ABCC1) was upregulated in the fibrotic liver tissues and activated HSCs...
January 17, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28098854/lsd1-sustains-estrogen-driven-endometrial-carcinoma-cell-proliferation-through-the-pi3k-akt-pathway-via-di-demethylating-h3k9-of-cyclin%C3%A2-d1
#2
Chunqin Chen, Yanan Wang, Shiyu Wang, Yuan Liu, Jiawen Zhang, Yuyao Xu, Zhenbo Zhang, Wei Bao, Sufang Wu
A recent study reported that histone lysine specific demethylase 1 (LSD1, KDM1A) is overexpressed in endometrioid endometrial carcinoma (EEC) and associated with tumor progression as well as poor prognosis. However, the physiological function and mechanism of LSD1 in endometrial cancer (EC) remains largely unknown. In this study, we demonstrate that β-estradiol (E2) treatment increased LSD1 expression via the GPR30/PI3K/AKT pathway in endometrial cancer cells. Both siGPR30 and the PI3K inhibitor LY294002 block this effect...
January 16, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28098843/perm-hypothesis-the-fundamental-machinery-able-to-elucidate-the-role-of-xenobiotics-and-hormesis-in-cell-survival-and-homeostasis
#3
REVIEW
Salvatore Chirumbolo, Geir Bjørklund
In this article the Proteasome, Endoplasmic Reticulum and Mitochondria (PERM) hypothesis is discussed. The complex machinery made by three homeostatic mechanisms involving the proteasome (P), endoplasmic reticulum (ER) and mitochondria (M) is addressed in order to elucidate the beneficial role of many xenobiotics, either trace metals or phytochemicals, which are spread in the human environment and in dietary habits, exerting their actions on the mechanisms underlying cell survival (apoptosis, cell cycle regulation, DNA repair and turnover, autophagy) and stress response...
January 15, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28098826/hair-growth-promoting-and-anticancer-effects-of-p21-activated-kinase-1-pak1-inhibitors-isolated-from-different-parts-of-alpinia-zerumbet
#4
Nozomi Taira, Binh Cao Quan Nguyen, Shinkichi Tawata
PAK1 (p21-activated kinase 1) is an emerging target for the treatment of hair loss (alopecia) and cancer; therefore, the search for PAK1 blockers to treat these PAK1-dependent disorders has received much attention. In this study, we evaluated the anti-alopecia and anticancer effects of PAK1 inhibitors isolated from Alpinia zerumbet (alpinia) in cell culture. The bioactive compounds isolated from alpinia were found to markedly promote hair cell growth. Kaempferol-3-O-β-d-glucuronide (KOG) and labdadiene, two of the isolated compounds, increased the proliferation of human follicle dermal papilla cells by approximately 117%-180% and 132%-226%, respectively, at 10-100 μM...
January 14, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28098814/thioridazine-a-non-antibiotic-drug-highly-effective-in-combination-with-first-line-anti-tuberculosis-drugs-against-any-form-of-antibiotic-resistance-of-mycobacterium-tuberculosis-due-to-its-multi-mechanisms-of-action
#5
REVIEW
Leonard Amaral, Miguel Viveiros
This review presents the evidence that supports the use of thioridazine (TZ) for the therapy of a pulmonary tuberculosis infection regardless of its antibiotic resistance status. The evidence consists of in vitro and ex vivo assays that demonstrate the activity of TZ against all encountered Mycobacterium tuberculosis (Mtb) regardless of its antibiotic resistance phenotype, as well as in vivo as a therapy for mice infected with multi-drug resistant strains of Mtb, or for human subjects infected with extensively drug resistant (XDR) Mtb...
January 14, 2017: Antibiotics
https://www.readbyqxmd.com/read/28098806/antibacterial-activities-and-possible-modes-of-action-of-acacia-nilotica-l-del-against-multidrug-resistant-escherichia-coli-and-salmonella
#6
Muhammad Bilal Sadiq, Joel Tarning, Tay Zar Aye Cho, Anil Kumar Anal
Medicinal plants are frequently used for the treatment of various infectious diseases. The objective of this study was to evaluate the antibacterial activity and mode of action of Acacia nilotica and the antibiogram patterns of foodborne and clinical strains of Escherichia coli and Salmonella. The mechanism of action of acacia extracts against E. coli and Salmonella was elucidated by observing morphological damages including cell integrity and cell membrane permeability, as well as changes in cell structures and growth patterns in kill-time experiments...
January 14, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28098598/science-of-intracrinology-in-postmenopausal-women
#7
Fernand Labrie, Alain Bélanger, Georges Pelletier, Céline Martel, David F Archer, Wulf H Utian
OBJECTIVE: To illustrate the marked differences between classical endocrinology that distributes hormones to all tissues of the body through the bloodstream and the science of intracrinology, whereby each cell of each peripheral tissue makes a small and appropriate amount of estrogens and androgens from the inactive precursor dehydroepiandrosterone (DHEA), DHEA being mainly of adrenal origin. Because only the inactivated sex steroids are released in the blood, influence in the other tissues is avoided...
January 16, 2017: Menopause: the Journal of the North American Menopause Society
https://www.readbyqxmd.com/read/28098499/inhibition-of-leishmania-infantum-trypanothione-reductase-by-diaryl-sulfide-derivatives
#8
Francesco Saccoliti, Gabriella Angiulli, Giovanni Pupo, Luca Pescatori, Valentina Noemi Madia, Antonella Messore, Gianni Colotti, Annarita Fiorillo, Luigi Scipione, Marina Gramiccia, Trentina Di Muccio, Roberto Di Santo, Roberta Costi, Andrea Ilari
The study presented here aimed at identifying a new class of compounds acting against Leishmania parasites, the causative agent of Leishmaniasis. For this purpose, the thioether derivatives of our in-house library have been evaluated in whole-cell screening assays in order to determine their in vitro activity against Leishmania protozoan. Among them, promising results have been achieved with compound RDS 777 (6-(sec-butoxy)-2-((3-chlorophenyl)thio)pyrimidin-4-amine) (IC50 = 29.43 µM), which is able to impair the mechanism of the parasite defence against the reactive oxygen species by inhibiting the trypanothione reductase (TR) with high efficiency (Ki 0...
December 2017: Journal of Enzyme Inhibition and Medicinal Chemistry
https://www.readbyqxmd.com/read/28098427/emergence-of-mania-in-two-middle-aged-patients-with-a-history-of-unipolar-treatment-refractory-depression-receiving-vagus-nerve-stimulation
#9
Naji C Salloum, Marie C Walker, Sunil Gangwani, Charles R Conway
OBJECTIVES: We report on two patients who experienced emergence of full manic symptoms while receiving vagal nerve stimulation (VNS). METHODS: Two patients, both with a well-documented and verified history of longstanding unipolar depression, were initiated on VNS for treatment of their severe major depressive episodes. RESULTS: The two patients had emergence of full manic symptoms after 8 and 9 months of VNS, respectively. Manic symptoms were adequately managed with standard treatments (mood stabilizer and electroconvulsive therapy) and VNS was continued in the two subjects for up to 5 years without any further occurrences of manic/hypomanic episodes...
January 18, 2017: Bipolar Disorders
https://www.readbyqxmd.com/read/28098416/motuporamine-derivatives-as-antimicrobial-agents-and-antibiotic-enhancers-against-resistant-gram-negative-bacteria
#10
Diane Borselli, Marine Blanchet, Jean-Michel Bolla, Aaron Muth, Kristen Skruber, Otto Phanstiel, Jean Michel Brunel
Dihydromotuporamine C and its derivatives were evaluated for their in vitro antimicrobial activities and antibiotic enhancement properties against Gram-negative bacteria and clinical isolates. The mechanism of action of one of these derivatives, MOTU-N44, was investigated against Enterobacter aerogenes by using fluorescent dyes to evaluate outer-membrane depolarization and permeabilization. Its efficiency correlated with inhibition of dye transport, thus suggesting that these molecules inhibit drug transporters by de-energization of the efflux pump rather than by direct interaction of the molecule with the pump...
January 18, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28098344/inhibition-of-oxytocin-and-vasopressin-neuron-activity-in-rat-hypothalamic-paraventricular-nucleus-by-relaxin-3-rxfp3-signalling
#11
Alan Kania, Anna Czerw, Agnieszka Grabowiecka, Camila de Ávila, Tomasz Blasiak, Zenon Rajfur, Marian H Lewandowski, Grzegorz Hess, Elena Timofeeva, Andrew L Gundlach, Anna Blasiak
KEY-POINTS: Relaxin-3 is a stress-responsive neuropeptide that acts at its cognate receptor, RXFP3, to alter behaviours including feeding. In this study, we have demonstrated a direct, RXFP3-dependent, inhibitory action of relaxin-3 on oxytocin and vasopressin PVN neuron electrical activity, a putative cellular mechanism of orexinergic actions of relaxin-3. We observed a Gαi/o -protein-dependent inhibitory influence of selective RXFP3 activation on PVN neuronal activity in vitro and demonstrated a direct action of RXFP3 activation on oxytocin and vasopressin PVN neurons, confirmed by their abundant expression of RXFP3 mRNA...
January 18, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28098206/protein-kinase-c-%C3%AE-signaling-is-required-for-dietary-prebiotic-induced-strengthening-of-intestinal-epithelial-barrier-function
#12
Richard Y Wu, Majd Abdullah, Pekka Määttänen, Ana Victoria C Pilar, Erin Scruten, Kathene C Johnson-Henry, Scott Napper, Catherine O'Brien, Nicola L Jones, Philip M Sherman
Prebiotics are non-digestible oligosaccharides that promote the growth of beneficial gut microbes, but it is unclear whether they also have direct effects on the intestinal mucosal barrier. Here we demonstrate two commercial prebiotics, inulin and short-chain fructo-oligosaccharide (scFOS), when applied onto intestinal epithelia in the absence of microbes, directly promote barrier integrity to prevent pathogen-induced barrier disruptions. We further show that these effects involve the induction of select tight junction (TJ) proteins through a protein kinase C (PKC) δ-dependent mechanism...
January 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28098184/infrared-laser-induced-gene-expression-for-tracking-development-and-function-of-single-c-elegans-embryonic-neurons
#13
Anupriya Singhal, Shai Shaham
Visualizing neural-circuit assembly in vivo requires tracking growth of optically resolvable neurites. The Caenorhabditis elegans embryonic nervous system, comprising 222 neurons and 56 glia, is attractive for comprehensive studies of development; however, embryonic reporters are broadly expressed, making single-neurite tracking/manipulation challenging. We present a method, using an infrared laser, for reproducible heat-dependent gene expression in small sublineages (one to four cells) without radiation damage...
January 18, 2017: Nature Communications
https://www.readbyqxmd.com/read/28098178/lithium-accumulates-in-neurogenic-brain-regions-as-revealed-by-high-resolution-ion-imaging
#14
Giulia Zanni, Wojciech Michno, Elena Di Martino, Anna Tjärnlund-Wolf, Jean Pettersson, Charlotte Elizabeth Mason, Gustaf Hellspong, Klas Blomgren, Jörg Hanrieder
Lithium (Li) is a potent mood stabilizer and displays neuroprotective and neurogenic properties. Despite extensive investigations, the mechanisms of action have not been fully elucidated, especially in the juvenile, developing brain. Here we characterized lithium distribution in the juvenile mouse brain during 28 days of continuous treatment that result in clinically relevant serum concentrations. By using Time-of-Flight Secondary Ion Mass Spectrometry- (ToF-SIMS) based imaging we were able to delineate temporospatial lithium profile throughout the brain and concurrent distribution of endogenous lipids with high chemical specificity and spatial resolution...
January 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28097896/a-new-nitrobenzoxadiazole-based-gstp1-1-inhibitor-with-a-previously-unheard-of-mechanism-of-action-and-high-stability
#15
Chiara Fulci, Dante Rotili, Anastasia De Luca, Lorenzo Stella, Blasco Morozzo Della Rocca, Mariantonietta Forgione, Veronica Di Paolo, Antonello Mai, Mattia Falconi, Luigi Quintieri, Anna M Caccuri
CONTEXT: The nitrobezoxadiazole derivative NBDHEX is a potent inhibitor of glutathione transferase P1-1 (GSTP1-1) endowed with outstanding anticancer activity in different tumor models. OBJECTIVE: To characterize by in vitro biochemical and in silico studies the NBDHEX analogues named MC2752 and MC2753. MATERIALS AND METHODS: Synthesis of MC2752 and MC2753, biochemical assays and in silico docking and normal-mode analyses. RESULTS: The presence of a hydrophobic moiety in the side chain of MC2753 confers unique features to this molecule...
December 2017: Journal of Enzyme Inhibition and Medicinal Chemistry
https://www.readbyqxmd.com/read/28097727/energetics-kinetics-and-pathway-of-snare-folding-and-assembly-revealed-by-optical-tweezers
#16
REVIEW
Yongli Zhang
Soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) are universal molecular engines that drive membrane fusion. Particularly, synaptic SNAREs mediate fast calcium-triggered fusion of neurotransmitter-containing vesicles with plasma membranes for synaptic transmission, the basis of all thought and action. During membrane fusion, complementary SNAREs located on two apposed membranes (often called t- and v-SNAREs) join together to assemble into a parallel four-helix bundle, releasing the energy to overcome the energy barrier for fusion...
January 18, 2017: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/28097679/abnormal-levels-of-seven-amino-neurotransmitters-in-depression-rat-brain-and-determination-by-hplc-fld
#17
Ting Cui, Hong-Mei Qiu, Dan Huang, Qi-Xin Zhou, Xiao-Yan Fu, Hai-Yan Li, Xin-Hui Jiang
The determination of amino acids with the actions-like neurotransmitters or modulators have been increasingly important for diagnose in many neuropsychiatric diseases. A rapid and simple high performance liquid chromatography with fluorescence detection (HPLC-FLD) was developed for simultaneous determination of seven amino acids: aspartate (Asp), glutamate (Glu), serine (Ser), glutamine (Gln), glycine (Gly), taurine (Tau) and γ-aminobutyric acid (GABA). Homoserine (Hse) was used as an internal standard (IS)...
January 18, 2017: Biomedical Chromatography: BMC
https://www.readbyqxmd.com/read/28097641/natural-products-diversity-of-marine-ascidians-tunicates-ascidiacea-and-successful-drugs-in-clinical-development
#18
REVIEW
Satheesh Kumar Palanisamy, N M Rajendran, Angela Marino
This present study reviewed the chemical diversity of marine ascidians and their pharmacological applications, challenges and recent developments in marine drug discovery reported during 1994-2014, highlighting the structural activity of compounds produced by these specimens. Till date only 5% of living ascidian species were studied from <3000 species, this study represented from family didemnidae (32%), polyclinidae (22%), styelidae and polycitoridae (11-12%) exhibiting the highest number of promising MNPs...
January 17, 2017: Natural Products and Bioprospecting
https://www.readbyqxmd.com/read/28097636/andrographolide-antibacterial-activity-against-common-bacteria-of-human-health-concern-and-possible-mechanism-of-action
#19
Malabika Banerjee, Debaprasad Parai, Subrata Chattopadhyay, Samir Kumar Mukherjee
Increasing bacterial resistance to common drugs is a major public health concern for the treatment of infectious diseases. Certain naturally occurring compounds of plant sources have long been reported to possess potential antimicrobial activity. This study was aimed to investigate the antibacterial activity and possible mechanism of action of andrographolide (Andro), a diterpenoid lactone from a traditional medicinal herb Andrographis paniculata. Extent of antibacterial action was assessed by minimal bactericidal concentration method...
January 17, 2017: Folia Microbiologica
https://www.readbyqxmd.com/read/28097478/study-of-the-influence-of-formulation-variables-in-bioadhesive-emulgels-using-response-surface-methodology
#20
Ana Ochoa-Andrade, M Emma Parente, Álvaro Jimenez-Kairuz, Lucía Boinbaser, Annibal Torregrosa
The aim of the present work was to study the main formulation variables that influence attributes of bioadhesive emulgels based on a combination of polymers, using response surface methodology (RSM). Bioadhesive products continue to gain attention in topical cutaneous administration as they allow long residence times on the application site, which is important when a long dermal action and a reduced product administration frequency are desired. A Box-Behnken design of experiments (DoE) was introduced to study the effect of formulation variables on quality attributes of the emulgels...
January 17, 2017: AAPS PharmSciTech
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