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https://www.readbyqxmd.com/read/28214650/2-methoxyestradiol-protects-against-igg-immune-complex-induced-acute-lung-injury-by-blocking-nf-%C3%AE%C2%BAb-and-ccaat-enhancer-binding-protein-%C3%AE-activities
#1
Chunguang Yan, Yanfei Shen, Qiqing Sun, Dong Yuan, Huifang Tang, Hongwei Gao
Increasing evidences indicate that 2-Methoxyestradiol (2ME2) plays an essential role in protecting against inflammatory responses. However, its effect on IgG immune complex (IC)-induced acute lung injury (ALI) remains enigmatic. In the study, by using i.p. administration of 2ME2, we evaluated its influence on IgG IC-induced pulmonary injury in mice. We found that during IgG IC-induced ALI, mice treated by 2ME2 displayed a substantial decrease in vascular permeability and neutrophil influx (represented by myeloperoxidase activity) when compared with their counterparts receiving vehicle treatment...
February 16, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28214646/new-rna-seq-approaches-for-the-study-of-bacterial-pathogens
#2
REVIEW
Antoine-Emmanuel Saliba, Sara C Santos, Jörg Vogel
Understanding how bacteria cause disease requires knowledge of which genes are expressed and how they are regulated during infection. While RNA-seq is now a routine method for gene expression analysis in bacterial pathogens, the past years have also witnessed a surge of novel RNA-seq based approaches going beyond standard mRNA profiling. These include variations of the technique to capture post-transcriptional networks controlled by small RNAs and to discover associated RNA-binding proteins in the pathogen itself...
February 16, 2017: Current Opinion in Microbiology
https://www.readbyqxmd.com/read/28214631/discovery-of-quinone-directed-antitumor-agents-selectively-bioactivated-by-nqo1-over-cpr-with-improved-safety-profile
#3
Jinlei Bian, Xiang Li, Nan Wang, Xingsen Wu, Qidong You, Xiaojin Zhang
In this work, we mainly focused on discovering compounds with good selectivity for NQO1 over CPR. The NQO1-mediated two-electron reduction of compounds would kill cancer cells selectively, while CPR-mediated one-electron reduction would induce potential hepatotoxicity. Several novel quinone-directed antitumor agents were discovered as specific NQO1 substrates through structure-activity relationship studies. Among them, compound 3,7,8-trimethylnaphtho[1,2-b]furan-4,5-dione (12b) emerged as the most specific substrate of the two-electron oxidoreductase NQO1 and could hardly be reduced by CPR...
February 6, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28214520/impact-of-copper-ligand-mutations-on-a-cupredoxin-with-a-green-copper-center
#4
Magali Roger, Giuliano Sciara, Frédéric Biaso, Elisabeth Lojou, Xie Wang, Marielle Bauzan, Marie-Thérèse Giudici-Orticoni, Alejandro Vila, Marianne Ilbert
Mononuclear cupredoxins contain a type 1 copper center with a trigonal or tetragonal geometry usually maintained by four ligands, a cystein, two histidines and a methionine. The recent discovery of new members of this family with unusual properties demonstrates, however, the versatility of this class of proteins. Changes in their ligand set lead to drastic variation in their metal site geometry and in the resulting spectroscopic and redox features. In our work, we report the identification of the copper ligands in the recently discovered cupredoxin AcoP...
February 15, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28214099/lymph-node-stroma-dynamics-and-approaches-for-their-visualization
#5
REVIEW
Rebecca Gentek, Marc Bajénoff
Lymphoid stromal cells are best known as the architectural cells of lymphoid organs. For decades, they have been considered as inert elements of the immune system but this view has changed dramatically in recent years, when it was discovered that they are endowed with critical immunoregulatory functions. It is now accepted that without them, the adaptive immune response would be compromised, if not abrogated entirely. Here, we review the function of the major lymphoid stromal cell types; the way they remodel upon inflammation; discuss the available tools to track their behavior; and introduce several methodological approaches that we believe will help improving our knowledge of these pivotal cell types...
February 14, 2017: Trends in Immunology
https://www.readbyqxmd.com/read/28214077/new-homoisoflavonoid-analogues-protect-cells-by-regulating-autophagy
#6
Li-She Gan, Lin-Wei Zeng, Xiang-Rong Li, Chang-Xin Zhou, Jie Li
As a special group of naturally occurring flavonoids, homoisoflavonoids have been discovered as active components of several traditional Chinese medicines for nourishing heart and mind. In this study, twenty homoisoflavonoid analogues, including different substitution groups on rings A and B, as well as heteroaromatic B ring, were synthesized and evaluated for their cardioprotective and neuroprotective activities. In a H2O2-induced H9c2 cardiomyocytes injury assay, nine homoisoflavonoid analogues showed promising activities in the same level as the positive control, diazoxide...
February 1, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28213952/down-regulation-of-kiaa1199-cemip-by-mir-216a-suppresses-tumor-invasion-and-metastasis-in-colorectal-cancer
#7
Dejun Zhang, Lei Zhao, Qiong Shen, Qing Lv, Min Jin, Hong Ma, Xiu Nie, Xiumei Zheng, Shaoyi Huang, Pengfei Zhou, Gang Wu, Tao Zhang
Colorectal cancer is one of the major causes of death from cancer. Metastasis is the leading cause of treatment failure, in which cancer stem cells and circulating tumor cells play crucial roles. Identifying the involved metastatic biomarkers and clarifying the regulation mechanisms are of great importance for targeting tumor metastasis. In the current research, we discovered that KIAA1199, a cell-migration inducing protein, showed higher expression in CD44+ cancer cells from metastatic compared with the paired primary tissues, and was upregulated in colorectal cancer and positively correlated with numbers and mesenchymal phenotype of circulating tumor cells, and predicted shorter progress-free survival...
February 18, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28213880/detection-of-digestive-malignancies-and-post-gastrectomy-complications-via-gastrointestinal-fluid-examination
#8
REVIEW
Lei Huang, Aman Xu
To date, gastric carcinoma (GC) is one of the common and fatal digestive malignancies worldwide. The prognosis of GC is not always satisfactory because of late diagnosis. Scholars are keen on discovering novel accurate and economical biomarkers in body liquids for GC screening to detect and evaluate the lesion before the results of imaging techniques are obtained. While traditional serum assays have limited sensitivity and specificity, gastrointestinal juice may provide relevant specific biomarkers because of its close contact with the tumor...
February 17, 2017: Frontiers of Medicine
https://www.readbyqxmd.com/read/28213856/inferior-vena-cava-system-anomalies-surgical-implications
#9
REVIEW
Javier González, Jeffrey J Gaynor, Luis F Albéniz, Gaetano Ciancio
PURPOSE OF REVIEW: The inferior vena cava (IVC) system is the major venous collecting blood network of the human body. This structure is formed in a complicated series of developmental stages between the fourth and eighth weeks of intrauterine life. Alterations in the developing process of the IVC system give rise to an array of different congenital variants or developmental anomalies. RECENT FINDINGS: IVC anomalies are uncommon, usually of little physiological consequence, and mostly discovered incidentally during cross-sectional imaging in otherwise healthy individuals...
February 2017: Current Urology Reports
https://www.readbyqxmd.com/read/28213853/to-pex-or-not-to-pex-what-to-do-for-the-contralateral-testis-when-a-nubbin-is-discovered
#10
REVIEW
John E Kehoe, Matthew S Christman
PURPOSE OF REVIEW: Testicular remnants or nubbins are commonly found in the evaluation and treatment of cryptorchidism. While much debate focuses on the management of the nubbin itself, there is also great uncertainty and variation in the management of the contralateral descended testis. Herein, we review the relevant literature informing the decision to perform a contralateral orchiopexy. RECENT FINDINGS: Although there is very little recent literature directly addressing the question, some studies have better characterized differences in practice, the risk of intravaginal torsion in the contralateral testis and potential consequences in the selection of technique...
February 2017: Current Urology Reports
https://www.readbyqxmd.com/read/28213771/a-novel-spiroindoline-targets-cell-cycle-and-migration-via-modulation-of-microtubule-cytoskeleton
#11
Naveen Kumar, Santanu Hati, Parthapratim Munshi, Subhabrata Sen, Seema Sehrawat, Shailja Singh
Natural product-inspired libraries of molecules with diverse architectures have evolved as one of the most useful tools for discovering lead molecules for drug discovery. In comparison to conventional combinatorial libraries, these molecules have been inferred to perform better in phenotypic screening against complicated targets. Diversity-oriented synthesis (DOS) is a forward directional strategy to access such multifaceted library of molecules. From a successful DOS campaign of a natural product-inspired library, recently a small molecule with spiroindoline motif was identified as a potent anti-breast cancer compound...
February 17, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28213625/8-nitro-cgmp-a-novel-protein-reactive-cnmp-and-its-emerging-roles-in-autophagy
#12
Hirokazu Arimoto, Daiki Takahashi
Nitric oxide (NO) raises the intracellular 3',5'-cyclic guanosine monophosphate (cGMP) level through the activation of soluble guanylate cyclase and, in the presence of reactive oxygen species (ROS), reacts with biomolecules to produce nitrated cGMP derivatives. 8-Nitro-cGMP was the first endogenous cGMP derivative discovered in mammalian cells (2007) and was later found in plant cells. Among the six nitrogen atoms in this molecule, the one in the nitro group (NO2) comes from NO. This chapter asserts that this newly found cGMP is undoubtedly one of the major physiological cNMPs...
February 18, 2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28213596/white-cell-count-in-the-normal-range-and-short-term-and-long-term-mortality-international-comparisons-of-electronic-health-record-cohorts-in-england-and-new-zealand
#13
Anoop Dinesh Shah, Simon Thornley, Sheng-Chia Chung, Spiros Denaxas, Rod Jackson, Harry Hemingway
OBJECTIVES: Electronic health records offer the opportunity to discover new clinical implications for established blood tests, but international comparisons have been lacking. We tested the association of total white cell count (WBC) with all-cause mortality in England and New Zealand. SETTING: Primary care practices in England (ClinicAl research using LInked Bespoke studies and Electronic health Records (CALIBER)) and New Zealand (PREDICT). DESIGN: Analysis of linked electronic health record data sets: CALIBER (primary care, hospitalisation, mortality and acute coronary syndrome registry) and PREDICT (cardiovascular risk assessments in primary care, hospitalisations, mortality, dispensed medication and laboratory results)...
February 17, 2017: BMJ Open
https://www.readbyqxmd.com/read/28213588/a-differential-autophagy-dependent-response-to-dna-double-strand-brakes-in-bone-marrow-mesenchymal-stem-cells-from-sporadic-als-patients
#14
Shane Wald-Altman, Edward Pichinuk, Or Kakhlon, Miguel Weil
Amyotrophic Lateral Sclerosis (ALS) is an incurable motor neurodegenerative disease caused by a diversity of genetic and environmental factors leading to neuromuscular degeneration and pathophysiological implications in non-neural systems. Our previous work showed abnormal transcriptional expression levels of biomarker genes in non-neuronal cell samples from ALS patients. The same genes proved to be differentially expressed in brain, spinal cord and muscle of the SOD1(G93A) ALS mouse model. These observations support the pathophysiological relevance of the ALS biomarkers discovered in human mesenchymal stem cells (hMSC) isolated from bone marrow samples of ALS patients (ALS-hMSC)...
February 16, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28213437/%C3%AE-synuclein-multiple-system-atrophy-prions
#15
Amanda L Woerman, Joel C Watts, Atsushi Aoyagi, Kurt Giles, Lefkos T Middleton, Stanley B Prusiner
Multiple system atrophy (MSA) is a rapidly progressive neurodegenerative disease arising from the misfolding and accumulation of the protein α-synuclein in oligodendrocytes, where it forms glial cytoplasmic inclusions (GCIs). Several years of studying synthetic α-synuclein fibrils has provided critical insight into the ability of α-synuclein to template endogenous protein misfolding, giving rise to fibrillar structures capable of propagating from cell to cell. However, more recent studies with MSA-derived α-synuclein aggregates have shown that they have a similar ability to undergo template-directed propagation, like PrP prions...
February 17, 2017: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/28213370/promiscuity-among-the-mraps
#16
Adrian J L Clark, Li F Chan
The melanocortin 2 receptor accessory protein (MRAP) was originally discovered to be an essential co-receptor for the ACTH receptor/melanocortin 2 receptor, and it physically interacts with this receptor and is required for receptor trafficking and ligand binding. A related molecule, MRAP2, is mainly expressed in the CNS and appears to have a role with the melanocortin 4 receptor. Consistent with this is the observation that a massively obese phenotype develops when the Mrap2 gene is deleted in mice. However, the characteristics of this phenotype differ from those of Mc4r deleted mice, and suggest that an additional role, possibly resulting from an interaction with other receptors is possible...
February 17, 2017: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/28213356/otx2-activity-at-distal-regulatory-elements-shapes-the-chromatin-landscape-of-group-3-medulloblastoma
#17
Gaylor Boulay, Mary E Awad, Nicolo Riggi, Tenley C Archer, Sowmya Iyer, Wannaporn E Boonseng, Nikki E Rossetti, Beverly Naigles, Shruthi Rengarajan, Angela Volorio, James C Kim, Jill P Mesirov, Pablo Tamayo, Scott L Pomeroy, Martin J Aryee, Miguel N Rivera
Medulloblastoma is the most frequent malignant pediatric brain tumor and is divided into at least four subgroups known as WNT, SHH, Group 3, and Group 4. Here, we characterized gene regulation mechanisms in the most aggressive subtype, Group 3 tumors, through genome-wide chromatin and expression profiling. Our results show that most active distal sites in these tumors are occupied by the transcription factor OTX2. Highly active OTX2-bound enhancers are often arranged as clusters of adjacent peaks and are also bound by the transcription factor NEUROD1...
February 17, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28213335/transformation-products-of-clindamycin-in-moving-bed-biofilm-reactor-mbbr
#18
Gordon T H Ooi, Monica Escola Casas, Henrik R Andersen, Kai Bester
Clindamycin is widely prescribed for its ability to treat a number of common bacterial infections. Thus, clindamycin enters wastewater via human excretion or disposal of unused medication and widespread detection of pharmaceuticals in rivers proves the insufficiency of conventional wastewater treatment plants in removing clindamycin. Recently, it has been discovered that attached biofilm reactors, e.g., moving bed biofilm reactors (MBBRs) obtain a higher removal of pharmaceuticals than conventional sludge wastewater treatment plants...
February 2, 2017: Water Research
https://www.readbyqxmd.com/read/28213207/epimetabolites-discovering-metabolism-beyond-building-and-burning
#19
REVIEW
Megan R Showalter, Tomas Cajka, Oliver Fiehn
Enzymatic transformations of primary, canonical metabolites generate active biomolecules that regulate important cellular and physiological processes. Roles include regulation of histone demethylation in epigenetics, inflammation in tissue injury, insulin sensitivity, cancer cell invasion, stem cell pluripotency status, inhibition of nitric oxide signaling and others. Such modified compounds, defined as epimetabolites, have functions distinct from classic hormones as well as removed from generic anabolism and catabolism...
February 14, 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/28213088/personalized-medicine-genetic-risk-prediction-of-drug-response
#20
REVIEW
Ge Zhang, Daniel W Nebert
Pharmacogenomics (PGx), a substantial component of "personalized medicine", seeks to understand each individual's genetic composition to optimize drug therapy -- maximizing beneficial drug response, while minimizing adverse drug reactions (ADRs). Drug responses are highly variable because innumerable factors contribute to ultimate phenotypic outcomes. Recent genome-wide PGx studies have provided some insight into genetic basis of variability in drug response. These can be grouped into three categories. [a] Monogenic (Mendelian) traits include early examples mostly of inherited disorders, and some severe (idiosyncratic) ADRs typically influenced by single rare coding variants...
February 14, 2017: Pharmacology & Therapeutics
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