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https://www.readbyqxmd.com/read/28239819/mir-137-and-its-target-tgfa-modulate-cell-growth-and-tumorigenesis-of-non-small-cell-lung-cancer
#1
X Liu, L Chen, X-D Tian, T Zhang
OBJECTIVE: MiR-137 has been reported to serve as a tumor suppressor in non-small cell lung cancer (NSCLC). However, the potential mechanism remains largely unclear. The present study aimed to explore the potential molecular mechanisms by which miR-137 regulated NSCLC. MATERIALS AND METHODS: Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to quantify the expression levels of miR-137 in NSCLC tissues and cell lines. Dual-luciferase reporter assay was employed to confirm the specificity of miR-137 target genes...
February 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28239780/sesamin-extends-lifespan-through-pathways-related-to-dietary-restriction-in-caenorhabditis-elegans
#2
Yumiko Nakatani, Yukie Yaguchi, Tomomi Komura, Masakazu Nakadai, Kenji Terao, Eriko Kage-Nakadai, Yoshikazu Nishikawa
PURPOSE: Sesamin, a polyphenolic compound found in sesame seeds, has been reported to exert a variety of beneficial health effects. We have previously reported that sesamin increases the lifespan of Caenorhabditis elegans. In this study, we investigated the molecular mechanisms underlying the longevity effect of sesamin in C. elegans. METHODS: Starting from three days of age, Caenorhabditis elegans animals were fed a standard diet alone or supplemented with sesamin...
February 26, 2017: European Journal of Nutrition
https://www.readbyqxmd.com/read/28239773/high-resolution-solid-state-nmr-spectroscopy-of-the-yersinia-pestis-outer-membrane-protein-ail-in-lipid-membranes
#3
Yong Yao, Samit Kumar Dutta, Sang Ho Park, Ratan Rai, L Miya Fujimoto, Andrey A Bobkov, Stanley J Opella, Francesca M Marassi
The outer membrane protein Ail (Adhesion invasion locus) is one of the most abundant proteins on the cell surface of Yersinia pestis during human infection. Its functions are expressed through interactions with a variety of human host proteins, and are essential for microbial virulence. Structures of Ail have been determined by X-ray diffraction and solution NMR spectroscopy, but those samples contained detergents that interfere with functionality, thus, precluding analysis of the structural basis for Ail's biological activity...
February 26, 2017: Journal of Biomolecular NMR
https://www.readbyqxmd.com/read/28239659/hsp90-regulation-of-fibroblast-activation-in-pulmonary-fibrosis
#4
Vishwaraj Sontake, Yunguan Wang, Rajesh K Kasam, Debora Sinner, Geereddy B Reddy, Anjaparavanda P Naren, Francis X McCormack, Eric S White, Anil G Jegga, Satish K Madala
Idiopathic pulmonary fibrosis (IPF) is a severe fibrotic lung disease associated with fibroblast activation that includes excessive proliferation, tissue invasiveness, myofibroblast transformation, and extracellular matrix (ECM) production. To identify inhibitors that can attenuate fibroblast activation, we queried IPF gene signatures against a library of small-molecule-induced gene-expression profiles and identified Hsp90 inhibitors as potential therapeutic agents that can suppress fibroblast activation in IPF...
February 23, 2017: JCI Insight
https://www.readbyqxmd.com/read/28239645/pml-promotes-metastasis-of-triple-negative-breast-cancer-through-transcriptional-regulation-of-hif1a-target-genes
#5
Manfredi Ponente, Letizia Campanini, Roberto Cuttano, Andrea Piunti, Giacomo A Delledonne, Nadia Coltella, Roberta Valsecchi, Alessandra Villa, Ugo Cavallaro, Linda Pattini, Claudio Doglioni, Rosa Bernardi
Elucidating the molecular basis of tumor metastasis is pivotal for eradicating cancer-related mortality. Triple-negative breast cancer (TNBC) encompasses a class of aggressive tumors characterized by high rates of recurrence and metastasis, as well as poor overall survival. Here, we find that the promyelocytic leukemia protein PML exerts a prometastatic function in TNBC that can be targeted by arsenic trioxide. We found that, in TNBC patients, constitutive HIF1A activity induces high expression of PML, along with a number of HIF1A target genes that promote metastasis at multiple levels...
February 23, 2017: JCI Insight
https://www.readbyqxmd.com/read/28239564/cancer-stem-cells-and-early-stage-basal-like-breast-cancer
#6
Pang-Kuo Lo, Benjamin Wolfson, Qun Zhou
Ductal carcinoma in situ (DCIS) is a category of early stage, non-invasive breast tumor defined by the intraductal proliferation of malignant breast epithelial cells. DCIS is a heterogeneous disease composed of multiple molecular subtypes including luminal, HER2 and basal-like types, which are characterized by immunohistochemical analyses and gene expression profiling. Following surgical and radiation therapies, patients with luminal-type, estrogen receptor-positive DCIS breast tumors can benefit from adjuvant endocrine-based treatment...
May 10, 2016: World Journal of Obstetrics and Gynecology
https://www.readbyqxmd.com/read/28239559/gene-profiling-the-window-of-implantation-microarray-analyses-from-human-and-rodent-models
#7
Jennifer L Herington, Yan Guo, Jeff Reese, Bibhash C Paria
Poor uterine receptivity leads to implantation defects or failure. Identification of uterine molecules crucial to uterine receptivity and/or embryo implantation provides the opportunity to design a diagnostic screening toolkit for uterine receptivity or targeted drug discovery for treating implantation-based infertility. In this regard, gene-profiling studies performed in humans and rodents have identified numerous genes involved in the transcriptional regulation of uterine receptivity and embryo implantation...
December 2016: J Reprod Health Med
https://www.readbyqxmd.com/read/28239489/insights-from-molecular-dynamics-simulations-for-computational-protein-design
#8
Matthew Carter Childers, Valerie Daggett
A grand challenge in the field of structural biology is to design and engineer proteins that exhibit targeted functions. Although much success on this front has been achieved, design success rates remain low, an ever-present reminder of our limited understanding of the relationship between amino acid sequences and the structures they adopt. In addition to experimental techniques and rational design strategies, computational methods have been employed to aid in the design and engineering of proteins. Molecular dynamics (MD) is one such method that simulates the motions of proteins according to classical dynamics...
February 1, 2017: Molecular Systems Design & Engineering
https://www.readbyqxmd.com/read/28239348/genetic-determinants-of-parkinson-s-disease-can-they-help-to-stratify-the-patients-based-on-the-underlying-molecular-defect
#9
REVIEW
Sara Redenšek, Maja Trošt, Vita Dolžan
Parkinson's disease (PD) is a sporadic progressive neurodegenerative brain disorder with a relatively strong genetic background. We have reviewed the current literature about the genetic factors that could be indicative of pathophysiological pathways of PD and their applications in everyday clinical practice. Information on novel risk genes is coming from several genome-wide association studies (GWASs) and their meta-analyses. GWASs that have been performed so far enabled the identification of 24 loci as PD risk factors...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28239160/insights-into-the-molecular-mechanisms-of-polygonum-multiflorum-thunb-induced-liver-injury-a-computational-systems-toxicology-approach
#10
Yin-Yin Wang, Jie Li, Zeng-Rui Wu, Bo Zhang, Hong-Bin Yang, Qin Wang, Ying-Chun Cai, Gui-Xia Liu, Wei-Hua Li, Yun Tang
An increasing number of cases of herb-induced liver injury (HILI) have been reported, presenting new clinical challenges. In this study, taking Polygonum multiflorum Thunb (PmT) as an example, we proposed a computational systems toxicology approach to explore the molecular mechanisms of HILI. First, the chemical components of PmT were extracted from 3 main TCM databases as well as the literature related to natural products. Then, the known targets were collected through data integration, and the potential compound-target interactions (CTIs) were predicted using our substructure-drug-target network-based inference (SDTNBI) method...
February 27, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28238906/fibulin-4-reduces-extracellular-matrix-production-and-suppresses-chondrocyte-differentiation-via-dkk1-mediated-canonical-wnt-%C3%AE-catenin-signaling
#11
Lei Shangguan, Guangzhi Ning, Zhuojing Luo, Yue Zhou
Fibulin-4 is an extracellular matrix (ECM) protein implicated in connective tissue development and elastic fiber formation. However, little is known about the underlying function of Fibulin-4 in cartilage development. The aim of this study was to investigate the role and probable mechanism of Fibulin-4 stimulation in ECM production and chondrocyte differentiation. Fibulin-4 has been observed to be abnormally elevated and matrix metalloproteinases 13 (MMP13) level was highly expressed in human osteoarthritis (OA) chondrocytes...
February 23, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28238819/alkylphospholipids-an-update-on-molecular-mechanisms-and-clinical-relevance
#12
REVIEW
Pablo Ríos-Marco, Carmen Marco, Xiomara Gálvez, Jose M Jiménez-López, María P Carrasco
Alkylphospholipid (APL) represent a new class of drugs which do not interact directly with DNA but act on the cell membrane where they accumulate and interfere with lipid metabolism and signalling pathways. This review summarizes the mode of action at the molecular level of these compounds. In this sense, a diversity of mechanisms has been suggested to explain the actions of clinically-relevant APLs, in particular, in cancer treatment. One consistently reported finding is that APLs reduce the biosynthesis of phosphatidylcholine (PC) by inhibiting the rate-limiting enzyme CTP:phosphocholine cytidylyltransferase (CT)...
February 23, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28238792/an-all-recombinant-protein-based-culture-system-specifically-identifies-hematopoietic-stem-cell-maintenance-factors
#13
Aki Ieyasu, Reiko Ishida, Takaharu Kimura, Maiko Morita, Adam C Wilkinson, Kazuhiro Sudo, Toshinobu Nishimura, Jun Ohehara, Yoko Tajima, Chen-Yi Lai, Makoto Otsu, Yukio Nakamura, Hideo Ema, Hiromitsu Nakauchi, Satoshi Yamazaki
Hematopoietic stem cells (HSCs) are considered one of the most promising therapeutic targets for the treatment of various blood disorders. However, due to difficulties in establishing stable maintenance and expansion of HSCs in vitro, their insufficient supply is a major constraint to transplantation studies. To solve these problems we have developed a fully defined, all-recombinant protein-based culture system. Through this system, we have identified hemopexin (HPX) and interleukin-1α as responsible for HSC maintenance in vitro...
February 10, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28238742/molecular-signatures-order-the-potency-of-topically-applied-anti-inflammatory-drugs-in-atopic-dermatitis-patients
#14
Emma Guttman-Yassky, Benjamin Ungar, Kunal Malik, Daniel Dickstein, Maria Suprun, Yeriel D Estrada, Hui Xu, Xiangyu Peng, Margeaux Oliva, Dan Todd, Tord Labuda, Mayte Suarez-Farinas, Robert Bissonnette
BACKGROUND: Atopic Dermatitis (AD) presents a large unmet need for treatments with better safety and efficacy. To facilitate development of topical therapeutics, we need an efficient model for assessing different formulations and concentrations. The "plaque model" has been successfully implemented in psoriasis, another common inflammatory disease, to assess efficacy of topical treatments. This model has not been validated for AD, which has higher placebo responses and less stable lesions than psoriasis...
February 23, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28238527/interferon-alpha-impairs-insulin-production-in-human-beta-cells-via-endoplasmic-reticulum-stress
#15
Angela Lombardi, Yaron Tomer
Despite substantial advances in the research exploring the pathogenesis of Type 1 Diabetes (T1D), the pathophysiological mechanisms involved remain unknown. We hypothesized in this study that interferon alpha (IFNα) participates in the early stages of T1D development by triggering endoplasmic reticulum (ER) stress. To verify our hypothesis, human islets and human EndoC-βH1 cells were exposed to IFNα and tested for ER stress markers, glucose stimulated insulin secretion (GSIS) and insulin content. IFNα treatment induced upregulation of ER stress markers including Binding immunoglobulin Protein, phospho-eukaryotic translation initiation factor 2α, spliced- X-box binding protein-1, C/EBP homologous protein and activating transcription factor 4...
February 23, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28238510/piperazines-as-nootropic-agents-new-derivatives-of-the-potent-cognition-enhancer-dm235-carrying-hydrophilic-substituents
#16
Maria Vittoria Martino, Luca Guandalini, Lorenzo Di Cesare Mannelli, Marta Menicatti, Gianluca Bartolucci, Silvia Dei, Dina Manetti, Elisabetta Teodori, Carla Ghelardini, Maria Novella Romanelli
The piperazine ring of the potent nootropic drug DM235 has been decorated with H-bond donor and acceptor groups (CH2OH, CH2OMe, CH2OCOMe, COOEt); the aim was to insert new functional groups, suitable for further chemical manipulation. The influence of these modifications on nootropic activity was assessed by means of the mouse passive avoidance test; some of the newly synthesized molecules (alcohol 7b, acetate 8b and ester 10d) showed interesting in vivo potency. This makes it possible to use these functional groups for adding other residues, in order to increase molecular diversity, or for anchoring a biotin group, to obtain compounds useful to capture the biological target...
February 16, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28238455/androgen-dependent-mechanisms-of-pro-angiogenic-networks-in-placental-and-tumor-development
#17
Veronika M Metzler, Simone de Brot, Robert S Robinson, Jennie N Jeyapalan, Emad Rakha, Thomas Walton, David S Gardner, Emma F Lund, Jonathan Whitchurch, Daisy Haigh, Jack M Lochray, Brian D Robinson, Cinzia Allegrucci, Rupert G Fray, Jenny L Persson, Niels Ødum, Regina R Miftakhova, Albert A Rizvanov, Ieuan A Hughes, Rieko Tadokoro-Cuccaro, David M Heery, Catrin S Rutland, Nigel P Mongan
The placenta and tumors share important characteristics, including a requirement to establish effective angiogenesis. In the case of the placenta, optimal angiogenesis is required to sustain the blood flow required to maintain a successful pregnancy, whereas in tumors establishing new blood supplies is considered a key step in supporting metastases. Therefore the development of novel angiogenesis inhibitors has been an area of active research in oncology. A subset of the molecular processes regulating angiogenesis are well understood in the context of both early placentation and tumorigenesis...
February 20, 2017: Placenta
https://www.readbyqxmd.com/read/28238438/arid2-modulates-dna-damage-response-in-human-hepatocellular-carcinoma-cells
#18
Atsushi Oba, Shu Shimada, Yoshimitsu Akiyama, Taketo Nishikawaji, Kaoru Mogushi, Hiromitsu Ito, Satoshi Matsumura, Arihiro Aihara, Yusuke Mitsunori, Daisuke Ban, Takanori Ochiai, Atsushi Kudo, Hiroshi Asahara, Atsushi Kaida, Masahiko Miura, Minoru Tanabe, Shinji Tanaka
BACKGROUND & AIMS: Recent genomic studies have identified frequent mutations of AT-rich interactive domain 2 (ARID2) in hepatocellular carcinoma (HCC), but it is not still understood how ARID2 exhibits tumor suppressor activities. METHODS: We established the ARID2 knockout human HCC cell lines by using CRISPR/Cas9 system, and investigated the gene expression profiles and biological functions. RESULTS: Bioinformatic analysis indicated that UV-response genes were negatively regulated in the ARID2 knockout cells, and they were sensitized to UV irradiation...
February 23, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28238425/reliable-screening-and-confirmation-of-156-multi-class-illegal-adulterants-in-dietary-supplements-based-on-extracted-common-ion-chromatograms-by-ultra-high-performance-liquid-chromatography-quadrupole-time-of-flight-mass-spectrometry
#19
Eun Hye Kim, Hee Seung Seo, Nam Yong Ki, Na-Hyun Park, Wonwoong Lee, Jung Ah Do, Sungkwan Park, Sun Young Baek, Bongjin Moon, Han Bin Oh, Jongki Hong
An analytical method for the reliable screening and confirmation of 156 illegal drugs (58 erectile dysfunction drugs, 49 synthetic steroids, 26 anabolic steroids, and 23 anti-histamine drugs) in supplementary diets using ultra-high-performance liquid chromatography coupled with quadrupole/time-of-flight mass spectrometry (UHPLC-Q/TOF-MS) was developed. Various types of supplements (liquid, capsule, powder, pill and tablet) with complicated matrices were pretreated by simple liquid-liquid extraction. The wide scope of 156 target compounds was effectively determined within 15min in the positive ion mode, detecting the compounds at a sub-ppb level...
February 20, 2017: Journal of Chromatography. A
https://www.readbyqxmd.com/read/28238402/design-synthesis-anticonvulsant-evaluation-and-docking-study-of-2-6-substituted-benzo-d-thiazol-2-ylcarbamoyl-methyl-1-4-substituted-phenyl-isothioureas
#20
Nadeem Siddiqui, Md Shamsher Alam, Meeta Sahu, Mohd Javed Naim, M Shahar Yar, Ozair Alam
In this paper, we report the synthesis of 2-[(6-substituted benzo[d]thiazol-2-ylcarbamoyl)methyl]-1-(4-substituted phenyl)isothiourea derivatives (4a-y) carrying active pharmacophores essential for anticonvulsant activity. The anticonvulsant activity was evaluated in vivo by maximal electroshock (MES) test and subcutaneous pentylenetetrazole (scPTZ) test in mice. Most of the compounds showed promising anticonvulsant activity. The most active compounds 4b and 4q were found active in both MES and scPTZ models, without signs of neurotoxicity...
February 17, 2017: Bioorganic Chemistry
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