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https://www.readbyqxmd.com/read/28742508/clinical-characterization-of-a-novel-calcium-sensing-receptor-genetic-alteration-in-a-greek-patient-with-autosomal-dominant-hypocalcemia-type-1
#1
Anna Papadopoulou, Evangelia Gole, Katerina Melachroinou, Theoni Trangas, Evaggelia Bountouvi, Anastasios Papadimitriou
OBJECTIVE: Autosomal dominant hypocalcemia (ADH) is a rare familial or sporadic syndrome associated with activating mutations in the calcium sensing receptor (CaSR) gene. The aim of this study was to assess the functional significance of a novel CaSR mutation and, moreover, to present the clinical characteristics and the bone mineral density (BMD) progression from early childhood to late puberty in a patient with ADH. DESIGN: Genetic analysis of the CaSR gene was performed in a patient who presented in the neonatal period with hypocalcemic seizures and biochemical features of ADH...
April 2017: Hormones: International Journal of Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28742148/hijacking-of-the-o-glcnaczyme-complex-by-the-htlv-1-tax-oncoprotein-facilitates-viral-transcription
#2
Damien Groussaud, Mostafa Khair, Armelle I Tollenaere, Laetitia Waast, Mei-Shiue Kuo, Marianne Mangeney, Christophe Martella, Yann Fardini, Solène Coste, Mouloud Souidi, Laurence Benit, Claudine Pique, Tarik Issad
The viral Tax oncoprotein plays a key role in both Human T-cell lymphotropic virus type 1 (HTLV-1)-replication and HTLV-1-associated pathologies, notably adult T-cell leukemia. Tax governs the transcription from the viral 5'LTR, enhancing thereby its own expression, via the recruitment of dimers of phosphorylated CREB to cAMP-response elements located within the U3 region (vCRE). In addition to phosphorylation, CREB is also the target of O-GlcNAcylation, another reversible post-translational modification involved in a wide range of diseases, including cancers...
July 24, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28740407/comparison-of-a-mouse-and-a-novel-human-scfv-snap-auristatin-f-drug-conjugate-with-potent-activity-against-egfr-overexpressing-human-solid-tumor-cells
#3
Mira Woitok, Diana Klose, Stefano Di Fiore, Wolfgang Richter, Christoph Stein, Gerrit Gresch, Elena Grieger, Stefan Barth, Rainer Fischer, Katharina Kolberg, Judith Niesen
Antibody-drug conjugates (ADCs) can deliver toxins to specific targets such as tumor cells. They have shown promise in preclinical/clinical development but feature stoichiometrically undefined chemical linkages, and those based on full-size antibodies achieve only limited tumor penetration. SNAP-tag technology can overcome these challenges by conjugating benzylguanine-modified toxins to single-chain fragment variables (scFvs) with 1:1 stoichiometry while preserving antigen binding. Two (human and mouse) scFv-SNAP fusion proteins recognizing the epidermal growth factor receptor (EGFR) were expressed in HEK 293T cells...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28735419/modulation-of-human-kv4-3-kchip2-channel-inactivation-kinetics-by-cytoplasmic-ca-2
#4
Christiane Groen, Robert Bähring
The transient outward current (I to) in the human heart is mediated by Kv4.3 channels complexed with Kv channel interacting protein (KChIP) 2, a cytoplasmic Ca(2+)-binding EF-hand protein known to modulate Kv4.3 inactivation gating upon heterologous co-expression. We studied Kv4.3 channels co-expressed with wild-type (wt) or EF-hand-mutated (ΔEF) KChIP2 in human embryonic kidney (HEK) 293 cells. Co-expression took place in the absence or presence of BAPTA-AM, and macroscopic currents were recorded in the whole-cell patch-clamp configuration with different free Ca(2+) concentrations in the patch-pipette...
July 22, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28735041/self-assembled-polypeptide-nanoparticles-for-intracellular-irinotecan-delivery
#5
N N Zashikhina, M V Volokitina, V A Korzhikov-Vlakh, I I Tarasenko, A Lavrentieva, T Scheper, E Rhuel, R V Orlova, T B Tennikova, E G Korzhikova-Vlakh
In this research poly(l-lysine)-b-poly(l-leucine) (PLys-b-PLeu) polymersomes were developed. It was shown that the size of nanoparticles depended on pH of self-assembly process and varied from 180 to 650nm. The biodegradation of PLys-b-PLeu nanoparticles was evaluated using in vitro polypeptide hydrolysis in two model enzymatic systems, as well as in human blood plasma. The experiments of the visualization of cellular uptake of rhodamine 6g-loaded and fluorescein-labeled nanoparticles were carried out, which approved the possibility of their penetration into the cells...
July 19, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28731329/generation-and-characterization-of-anti-vglut-nanobodies-acting-as-inhibitors-of-transport
#6
Stephan Schenck, Laura Kunz, Daniela Sahlender, Els Pardon, Eric R Geertsma, Iaroslav Savtchouk, Toshiharu Suzuki, Yvonne Neldner, Saša Štefanić, Jan Steyaert, Andrea Volterra, Raimund Dutzler
The uptake of glutamate by synaptic vesicles is mediated by vesicular glutamate transporters (VGLUTs). The central role of these transporters in excitatory neurotransmission underpins their importance as pharmacological targets. Although several compounds inhibit VGLUTs, highly specific inhibitors were so far unavailable, thus limiting applications to in vitro experiments. Besides their potential in pharmacology, specific inhibitors would also be beneficial for the elucidation of transport mechanisms. To overcome this shortage, we generated nanobodies (Nbs) by immunization of a llama with purified rat VGLUT1 and subsequent selection of binders from a phage display library...
July 21, 2017: Biochemistry
https://www.readbyqxmd.com/read/28728976/effect-of-alkylaminophenols-on-growth-inhibition-and-apoptosis-of-bone-cancer-cells
#7
Phuong Doan, Tien Nguyen, Olli Yli-Harja, Nuno R Candeias, Meenakshisundaram Kandhavelu
In this work, we report the anticancer properties of a series of 11 chemically synthesized alkylaminophenols against human osteosarcoma U2OS tumor cell line. Several assays including cytotoxicity, inhibitor kinetic study, cell migration, Annexin-V/PI double staining, reactive oxygen species (ROS) and caspase 3/7 assays were conducted on this cell line. Cytotoxic 2-((3,4-dihydroquinolin-1(2H)-yl)(p-tolyl)methyl)phenol was determined to have an IC50 value of 36.6μM against U2OS cells and it also inhibits the cell growth in time-dependent manner...
July 17, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28727371/mir-483-5p-promotes-prostate-cancer-cell-proliferation-and-invasion-by-targeting-rbm5
#8
Zhi-Gang Yang, Xu-Dong Ma, Zhao-Hui He, Ying-Xin Guo
OBJECTIVE: miR-483-5p has been identified as a miRNA oncogene in certain cancers. However, its role in prostate cancer has not been sufficiently investigated. In this study, we investigated the role of miR-483-5p in prostate cancer and examined RBM5 regulation by miR-483-5p. MATERIAL AND METHODS: Expression levels of miR-483-5p were determined by quantitative real-time PCR. The effect of miR-483-5p on proliferation was evaluated by MTT assay, cell invasion was evaluated by trans-well invasion assays, and target protein expression was determined by western blotting in LNCaP, DU-145, and PC-3 cells...
June 14, 2017: International Braz J Urol: Official Journal of the Brazilian Society of Urology
https://www.readbyqxmd.com/read/28720717/sting-is-an-essential-mediator-of-the-ku70-mediated-production-of-ifn-%C3%AE-1-in-response-to-exogenous-dna
#9
Hongyan Sui, Ming Zhou, Hiromi Imamichi, Xiaoli Jiao, Brad T Sherman, H Clifford Lane, Tomozumi Imamichi
We previously identified Ku70, a subunit of a DNA repair protein complex, as a cytosolic DNA sensor that induces the production of interferon-λ1 (IFN-λ1) by human primary cells and cell lines. IFN-λ1 is a type III IFN and has similar antiviral activity to that of the type I IFNs (IFN-α and IFN-β). We observed that human embryonic kidney (HEK) 293T cells, which are deficient in the innate immune adaptor protein STING (stimulator of IFN genes), did not produce IFN-λ1 in response to DNA unless they were reconstituted with STING...
July 18, 2017: Science Signaling
https://www.readbyqxmd.com/read/28712477/phytochemical-analysis-and-cytotoxicity-evaluation-of-kelussia-odoratissima-mozaff
#10
Amir Abbas Momtazi, Omid Askari-Khorasgani, Elham Abdollahi, Hojjat Sadeghi-Aliabadi, Forough Mortazaeinezhad, Amirhossein Sahebkar
BACKGROUND: Kelussia odoratissima Mozaff. (Apiaceae) is an edible, indigenous, and ethnomedicinal plant that grows only in Iran. Although antioxidant and anti-inflammatory properties of K. odoratissima have been reported, cytotoxic activity of this plant has not been investigated previously. OBJECTIVE: This study aims to evaluate the cytotoxicity of K. odoratissima leaf extract against a panel of human cancer cell lines. A secondary aim was to perform a phytochemical analysis of the plant's leaf oil...
June 2017: Journal of Acupuncture and Meridian Studies
https://www.readbyqxmd.com/read/28709125/ciprofloxacin-nitroxide-hybrids-with-potential-for-biofilm-control
#11
Anthony D Verderosa, César de la Fuente-Núñez, Sarah C Mansour, Jicong Cao, Timothy K Lu, Robert E W Hancock, Kathryn E Fairfull-Smith
As bacterial biofilms display extreme tolerance to conventional antibiotic treatments, it has become imperative to develop new antibacterial strategies with alternative mechanisms of action. Herein, we report the synthesis of a series of ciprofloxacin-nitroxide conjugates and their corresponding methoxyamine derivatives in high yield. This was achieved by linking various nitroxides or methoxyamines to the secondary amine of the piperazine ring of ciprofloxacin using amide bond coupling. Biological evaluation of the prepared compounds on preformed P...
June 28, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28708759/long-noncoding-rna-mrak009713-is-a-novel-regulator-of-neuropathic-pain-in-rats
#12
Guilin Li, Huaide Jiang, Chaoran Zheng, Gaochun Zhu, Yurong Xu, Xuan Sheng, Bing Wu, Jingjing Guo, Shuanghua Zhu, Yuting Zhan, Weijian Lin, Rui Ding, Chunping Zhang, Shuangmei Liu, Lifang Zou, Zhihua Yi, Shangdong Liang
Long noncoding RNAs (lncRNAs) have been implicated in neuropathy. Here we identify and validate an lncRNA, MRAK009713, as a primary regulator of neuropathic pain in chronic constriction injury (CCI) rats. MRAK009713 expression was markedly increased in CCI rats associated with enhanced pain behaviors and small interfering RNA (siRNA) against MRAK009713 significantly reduced both mechanical and thermal hyperalgesia in the CCI rats. MRAK009713 is predicted to interact with the nociceptive P2X3 receptor by CatRAPID, a bioinformatics technology...
July 11, 2017: Pain
https://www.readbyqxmd.com/read/28708400/contribution-of-mate1-to-renal-secretion-of-the-nmda-receptor-antagonist-memantine
#13
Fabian Müller, Dietmar Weitz, Volker Derdau, Martin Sandvoss, Katharina Mertsch, Jörg König, Martin F Fromm
The weak base memantine is actively secreted into urine, however the underlying mechanisms are insufficiently understood. Potential candidates involved in memantine renal secretion are organic cation transporter 2 (OCT2) and multidrug and toxin extrusion proteins (MATE1, MATE2-K). The aim of this in vitro study was the examination of the interaction of memantine with OCT2 and MATEs. Memantine transporter inhibition and transport were examined in HEK cells expressing human OCT2, MATE1, or MATE2-K. Monolayers of single- (MDCK-OCT2, MDCK-MATE1) and double-transfected MDCK cells (MDCK-OCT2-MATE1) were used for studies on vectorial, basal to apical memantine transport...
July 14, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28706458/electrophysiological-characteristics-of-r47w-and-a298t-mutations-in-clc-1-of-myotonia-congenita-patients-and-evaluation-of-clinical-features
#14
Hyung Jin Chin, Chan Hyeong Kim, Kotdaji Ha, Jin Hong Shin, Dae-Seong Kim, Insuk So
Myotonia congenita (MC) is a genetic disease that displays impaired relaxation of skeletal muscle and muscle hypertrophy. This disease is mainly caused by mutations of CLCN1 that encodes human skeletal muscle chloride channel (CLC-1). CLC-1 is a voltage gated chloride channel that activates upon depolarizing potentials and play a major role in stabilization of resting membrane potentials in skeletal muscle. In this study, we report 4 unrelated Korean patients diagnosed with myotonia congenita and their clinical features...
July 2017: Korean Journal of Physiology & Pharmacology
https://www.readbyqxmd.com/read/28706328/trypsin-inhibitors-demonstrate-antioxidant-activities-inhibit-a549-cell-proliferation-and-increase-activities-of-reactive-oxygen-species-scavenging-enzymes
#15
Tooba Naz Shamsi, Romana Parveen, Sadaf Fatima
OBJECTIVES: Protease inhibitors are one of the most promising and investigated subjects for their role in pharmacognostical and pharmacological studies. This study aimed to investigate antineoplastic and antioxidant activity of trypsin inhibitors (TIs) isolated from three plant sources and their inhibitory role in the cell line. MATERIALS AND METHODOLOGY: TIs were obtained from different plant sources. Antineoplastic potential on adenocarcinoma human alveolar basal epithelial cell line (A549) and normal Human Embryonic Kidney (HEK) was determined using MTT assay...
March 2017: Indian Journal of Pharmacology
https://www.readbyqxmd.com/read/28698143/snail-transcription-factor-nls-and-importin-%C3%AE-1-regulate-the-subcellular-localization-of-cathepsin-l-and-cux1
#16
Liza J Burton, Veronica Henderson, Latiffa Liburd, Valerie A Odero-Marah
Several recent studies have highlighted an additional unexpected localization and site of action for Cathepsin L (Cat L) protease within the nucleus in breast, colon and prostate cancer, however, its role in the nucleus was unclear. It was proposed to mediate proteolytic processing of the transcription factor CCAAT-displacement protein/cut homeobox transcription factor (Cux1) from the full-length p200 isoform to generate the p110 and p90 isoforms, of which the p110 isoform was shown to act as a cell cycle regulator to accelerate entry into the S phase...
July 8, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28696589/in-vitro-activity-of-the-interaction-between-taxifolin-dihydroquercetin-and-pyrimethamine-against-toxoplasma-gondii
#17
Daniel A Abugri, William H Witola, Albert E Russell, Roberta M Troy
Toxoplasmosis is one of the most neglected zoonotic foodborne parasitic diseases that cause public health and socio-economic concern worldwide. The current drugs used for the treatment of toxoplasmosis have been identified to have clinical limitations. Hence, new drugs are urgently needed to eradicate T.gondii infections globally. Here, an in vitro anti-Toxoplasma gondii activity of taxifolin (dihydroquercetin) and dihydrofolate inhibitor (pyrimethamine) alone and in combination with a fixed concentration of pyrimethamine were investigated against the rapidly proliferating T...
July 11, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28696429/glud1-linked-to-schizophrenia-controls-the-burst-firing-of-dopamine-neurons
#18
N Benamer, F Marti, R Lujan, R Hepp, T G Aubier, A A M Dupin, G Frébourg, S Pons, U Maskos, P Faure, Y A Hay, B Lambolez, L Tricoire
Human mutations of the GRID1 gene encoding the orphan delta1 glutamate receptor-channel (GluD1) are associated with schizophrenia but the explicit role of GluD1 in brain circuits is unknown. Based on the known function of its paralog GluD2 in cerebellum, we searched for a role of GluD1 in slow glutamatergic transmission mediated by metabotropic receptor mGlu1 in midbrain dopamine neurons, whose dysfunction is a hallmark of schizophrenia. We found that an mGlu1 agonist elicits a slow depolarizing current in HEK cells co-expressing mGlu1 and GluD1, but not in cells expressing mGlu1 or GluD1 alone...
July 11, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28696308/tsrna-signatures-in-cancer
#19
Veronica Balatti, Giovanni Nigita, Dario Veneziano, Alessandra Drusco, Gary S Stein, Terri L Messier, Nicholas H Farina, Jane B Lian, Luisa Tomasello, Chang-Gong Liu, Alexey Palamarchuk, Jonathan R Hart, Catherine Bell, Mariantonia Carosi, Edoardo Pescarmona, Letizia Perracchio, Maria Diodoro, Andrea Russo, Anna Antenucci, Paolo Visca, Antonio Ciardi, Curtis C Harris, Peter K Vogt, Yuri Pekarsky, Carlo M Croce
Small, noncoding RNAs are short untranslated RNA molecules, some of which have been associated with cancer development. Recently we showed that a class of small RNAs generated during the maturation process of tRNAs (tRNA-derived small RNAs, hereafter "tsRNAs") is dysregulated in cancer. Specifically, we uncovered tsRNA signatures in chronic lymphocytic leukemia and lung cancer and demonstrated that the ts-4521/3676 cluster (now called "ts-101" and "ts-53," respectively), ts-46, and ts-47 are down-regulated in these malignancies...
July 10, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28694808/mycobacterium-tuberculosis-dosr-regulon-gene-rv2004c-encodes-a-novel-antigen-with-pro-inflammatory-functions-and-potential-diagnostic-application-for-detection-of-latent-tuberculosis
#20
Sankara Narayana Doddam, Vidyullatha Peddireddy, Niyaz Ahmed
Approximately 1.7 billion people in the world harbor latent Mycobacterium tuberculosis (Mtb) with a substantial risk of progression to clinical outcome. Containment of these seed beds of Mtb is essential to eliminate tuberculosis completely in high burden settings such as India. Hence, there is an urgent need for the identification of new serological markers for detection or vaccine candidates to prevent latent tuberculosis infection (LTBI). DosR regulon antigens of Mtb might serve as attractive targets for LTBI diagnosis or vaccine development as they are specifically expressed and are upregulated during latent phase...
2017: Frontiers in Immunology
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