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https://www.readbyqxmd.com/read/28102676/novel-antitumor-platinum-ii-conjugates-containing-the-nonsteroidal-anti-inflammatory-agent-diclofenac-synthesis-and-dual-mechanisms-of-antiproliferative-effects
#1
Francesco Paolo Intini, Juraj Zajac, Vojtech Novohradsky, Teresa Saltarella, Concetta Pacifico, Viktor Brabec, Giovanni Natile, Jana Kasparkova
One concept how to improve anticancer effects of conventional metallodrugs consists in conjugation of these compounds with other biologically (antitumor) active agents, acting by a different mechanism. Here, we present synthesis, biological effects, and mechanisms of action of new Pt(II) derivatives containing one or two nonsteroidal anti-inflammatory diclofenac (DCF) ligands also known for their antitumor effects. The antiproliferative properties of these metallic conjugates show that these compounds are potent and cancer cell selective cytotoxic agents exhibiting activity in cisplatin resistant and the COX-2 positive tumor cell lines...
January 19, 2017: Inorganic Chemistry
https://www.readbyqxmd.com/read/28102674/2d-ir-spectroscopy-shows-that-optimised-dna-minor-groove-binding-of-hoechst33258-follows-an-induced-fit-model
#2
Lennart A I Ramakers, Gordon Hithell, John J May, Gregory M Greetham, Paul M Donaldson, Michael Towrie, Anthony W Parker, Glenn A Burley, Neil T Hunt
The induced fit binding model describes a conformational change occurring when a small molecule binds to its biomacromolecular target. The result is enhanced non-covalent interactions between ligand and biomolecule. Induced fit is well-established for small molecule-protein interactions, but its relevance to small molecule-DNA binding is less clear. We investigate the molecular determinants of Hoechst33258 binding to its preferred A-tract sequence relative to a sub-optimal alternating A-T sequence. Results from 2-dimensional infrared spectroscopy, which is sensitive to H-bonding and molecular structure changes, show that Hoechst33258 binding results in loss of minor groove spine of hydration in both sequences, but an additional perturbation of the base propeller twists occurs in the A-tract binding region...
January 19, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28102569/human-%C3%AE-defensin-3-increases-the-tlr9-dependent-response-to-bacterial-dna
#3
Sarah L McGlasson, Fiona Semple, Heather MacPherson, Mohini Gray, Donald J Davidson, Julia R Dorin
Human β-defensin 3 (hBD3) is a cationic antimicrobial peptide with potent bactericidal activity in vitro. HBD3 is produced in response to pathogen challenge and can modulate immune responses. The amplified recognition of self-DNA by human plasmacytoid dendritic cells has been previously reported, but we show here that hBD3 preferentially enhances the response to bacterial DNA in mouse Flt-3 induced dendritic cells (FLDCs) and in human peripheral blood mononuclear cells. We show the effect is mediated through TLR9 and although hBD3 significantly increases the cellular uptake of both E...
January 19, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28102367/interspecies-cathelicidin-comparison-reveals-divergence-in-antimicrobial-activity-tlr-modulation-chemokine-induction-and-regulation-of-phagocytosis
#4
Maarten Coorens, Maaike R Scheenstra, Edwin J A Veldhuizen, Henk P Haagsman
Cathelicidins are short cationic peptides initially described as antimicrobial peptides, which can also modulate the immune system. Because most findings have been described in the context of human LL-37 or murine CRAMP, or have been investigated under varying conditions, it is unclear which functions are cathelicidin specific and which functions are general cathelicidin properties. This study compares 12 cathelicidins from 6 species under standardized conditions to better understand the conservation of cathelicidin functions...
January 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28102315/methyl-cytosine-driven-structural-changes-enhance-adduction-kinetics-of-an-exon-7-fragment-of-the-p53-gene
#5
Spundana Malla, Karteek Kadimisetty, You-Jun Fu, Dharamainder Choudhary, John B Schenkman, James F Rusling
Methylation of cytosine (C) at C-phosphate-guanine (CpG) sites enhances reactivity of DNA towards electrophiles. Mutations at CpG sites on the p53 tumor suppressor gene that can result from these adductions are in turn correlated with specific cancers. Here we describe the first restriction-enzyme-assisted LC-MS/MS sequencing study of the influence of methyl cytosines (MeC) on kinetics of p53 gene adduction by model metabolite benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide (BPDE), using methodology applicable to correlate gene damage sites for drug and pollutant metabolites with mutation sites...
January 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28102297/whsc1l1-mediated-egfr-mono-methylation-enhances-the-cytoplasmic-and-nuclear-oncogenic-activity-of-egfr-in-head-and-neck-cancer
#6
Vassiliki Saloura, Theodore Vougiouklakis, Makda Zewde, Xiaolan Deng, Kazuma Kiyotani, Jae-Hyun Park, Yo Matsuo, Mark Lingen, Takehiro Suzuki, Naoshi Dohmae, Ryuji Hamamoto, Yusuke Nakamura
While multiple post-translational modifications have been reported to regulate the function of epidermal growth factor receptor (EGFR), the effect of protein methylation on its function has not been well characterized. In this study, we show that WHSC1L1 mono-methylates lysine 721 in the tyrosine kinase domain of EGFR, and that this methylation leads to enhanced activation of its downstream ERK cascade without EGF stimulation. We also show that EGFR K721 mono-methylation not only affects the function of cytoplasmic EGFR, but also that of nuclear EGFR...
January 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28102011/local-myogenic-pulp-derived-cell-injection-enhances-craniofacial-muscle-regeneration-in-vivo
#7
J E Jung, M J Song, S Shin, Y J Choi, K H Kim, C J Chung
OBJECTIVES: To enhance myogenic differentiation in pulp cells isolated from extracted premolars by epigenetic modification using a DNA demethylation agent, 5-aza-2'-deoxycytidine (5-Aza), and to evaluate the potent stimulatory effect of 5-Aza-treated pulp cell injection for craniofacial muscle regeneration in vivo. SETTING AND SAMPLE POPULATION: Pulp cells were isolated from premolars extracted for orthodontic purposes from four adults (age range, 18-22.1 years)...
February 2017: Orthodontics & Craniofacial Research
https://www.readbyqxmd.com/read/28101820/insulin-insulin-like-growth-factor-1-signalling-iis-based-regulation-of-lifespan-across-species
#8
REVIEW
Rebecca Mathew, Manika Pal Bhadra, Utpal Bhadra
An organism's well-being is facilitated by numerous molecular and biochemical pathways that ensure homeostasis within cells and tissues. Aging causes a gradual let-down in the maintenance of homeostasis due to various endogenous and environmental challenges, leading to amassing of damages, functional deterioration of different tissues and vulnerability to ailments. Nutrient sensing pathways that maintain glucose homeostasis in body are involved in regulation of aging. Insulin/insulin-like growth factor-1 (IGF-1) signalling (IIS) pathway was the first nutrient sensing pathway discovered to affect the aging process...
January 18, 2017: Biogerontology
https://www.readbyqxmd.com/read/28101802/cold-pcr-technologies-in-the-area-of-personalized-medicine-methodology-and-applications
#9
REVIEW
Florence Mauger, Alexandre How-Kit, Jörg Tost
Somatic mutations bear great promise for use as biomarkers for personalized medicine, but are often present only in low abundance in biological material and are therefore difficult to detect. Many assays for mutation analysis in cancer-related genes (hotspots) have been developed to improve diagnosis, prognosis, prediction of drug resistance, and monitoring of the response to treatment. Two major approaches have been developed: mutation-specific amplification methods and methods that enrich and detect mutations without prior knowledge on the exact location and identity of the mutation...
January 18, 2017: Molecular Diagnosis & Therapy
https://www.readbyqxmd.com/read/28101801/identification-of-changes-in-the-human-papilloma-virus-16-hpv16-genome-during-early-dissemination-of-cervical-cancer-cells-may-complement-histological-diagnosis-of-lymph-node-metastasis
#10
Anirban Roychowdhury, Sudip Samadder, Md Saimul Islam, Kalyansree Chaudhury, Anup Roy, Dipanwita Banerjee, Ranajit Mandal, Partha S Basu, Susanta Roychoudhury, Chinmay Kumar Panda
Cancer of the uterine cervix (CACX) is one of the most common carcinoma affecting women worldwide. During treatment, histologically lymph node (LN) metastasis and presence of HPV DNA in blood plasma act as a major prognostic factor. Despite the lack of apparent LN involvement, some early-invasive CACX patients have shown recurrences and poor survival. This is suggestive of undetected early dissemination of cancer cells characterized by presence of HPV DNA in histologically non-metastatic LNs which finally progresses into histologically visible metastasis...
January 19, 2017: Pathology Oncology Research: POR
https://www.readbyqxmd.com/read/28101269/metagenomic-approaches-to-identify-novel-organisms-from-the-soil-environment-in-a-classroom-setting
#11
Sadia J Rahman, Trevor C Charles, Parjit Kaur
Molecular Microbial Metagenomics is a research-based undergraduate course developed at Georgia State University. This semester-long course provides hands-on research experience in the area of microbial diversity and introduces molecular approaches to study diversity. Students are part of an ongoing research project that uses metagenomic approaches to isolate clones containing 16S ribosomal ribonucleic acid (rRNA) genes from a soil metagenomic library. These approaches not only provide a measure of microbial diversity in the sample but may also allow discovery of novel organisms...
December 2016: Journal of Microbiology & Biology Education: JMBE
https://www.readbyqxmd.com/read/28101214/parp-1-may-be-involved-in-angiogenesis-in-epithelial-ovarian-cancer
#12
Wei Wei, Yan Li, Shuqing Lv, Cancan Zhang, Yongjie Tian
Poly (ADP-ribose) polymerase 1 (PARP-1) is involved in DNA repair and has been implicated in chemoresistance. The present study investigated whether PARP-1 promotes angiogenesis in ovarian cancer. PARP-1 and vascular endothelial growth factor A (VEGF-A) expression and CD34(+) microvascular density (MVD) were assessed using immunohistochemistry in 60 human epithelial ovarian cancer specimens. PARP-1 was stably knocked-down in SKOV3 cells using a specific small interfering RNA (siRNA); angiogenic capacity was assessed using the human umbilical vein endothelial cell (HUVEC) tubule formation assay; and PARP-1 and VEGF-A expression were examined by reverse transcription-quantitative polymerase chain reaction, western blotting and ELISA...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28100914/tet-mediated-hydroxymethylcytosine-at-the-ppar%C3%AE-locus-is-required-for-initiation-of-adipogenic-differentiation
#13
Y Yoo, J H Park, C Weigel, D B Liesenfeld, D Weichenhan, C Plass, D-G Seo, A M Lindroth, Y J Park
BACKGROUND/OBJECTIVES: Adipose tissue is one of the main organs regulating energy homeostasis, via energy storage as well as endocrine function. The adipocyte cell number is largely determined by adipogenesis. While the molecular mechanism of adipogenesis has been extensively studied, its role in dynamic DNA methylation plasticity remains unclear. Recently, it has been shown that Tet methylcytosine dioxygenase (TET) are catalytically capable of oxidizing DNA 5-methylcytosine (5-mC) to 5-hydroxymethylcytosine (5-hmC) towards a complete removal of the methylated cytosine...
January 19, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28100749/promoted-interaction-of-c-ebp%C3%AE-with-demethylated-cxcr3-gene-promoter-contributes-to-neuropathic-pain-in-mice
#14
Bao-Chun Jiang, Li-Na He, Xiao-Bo Wu, Hui Shi, Wen-Wen Zhang, Zhi-Jun Zhang, De-Li Cao, Chun-Hua Li, Jun Gu, Yong-Jing Gao
: DNA methylation has been implicated in the pathogenesis of chronic pain. However, the specific genes regulated by DNA methylation under neuropathic pain condition remain largely unknown. Here we investigated how chemokine receptor CXCR3 is regulated by DNA methylation and how it contributes to neuropathic pain induced by spinal nerve ligation (SNL) in mice. SNL increased Cxcr3 mRNA and protein expression in the neurons of the spinal cord. Meanwhile, the CpG (5'-cytosine-phosphate-guanine-3') island in the Cxcr3 gene promoter region was demethylated, and the expression of DNA methyltransferase 3b (DNMT3b) was decreased...
January 18, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28100707/the-rla1-smos1-transcription-factor-functions-with-osbzr1-to-regulate-brassinosteroid-signaling-and-rice-architecture
#15
Shenglong Qiao, Shiyong Sun, Linlin Wang, Zhihua Wu, Chengxiang Li, Xiaoming Li, Tao Wang, Linna Leng, Weisheng Tian, Tiegang Lu, Xuelu Wang
Brassinosteroids (BRs) are plant-specific steroid hormones that control plant growth and development. Recent studies have identified key components of the BR signaling pathway in Arabidopsis thaliana and in rice (Oryza sativa); however, the mechanism of BR signaling in rice, especially downstream of GSK3/SHAGGY-like kinase (GSK2), remains unclear. Here we identified a BR-insensitive rice mutant, reduced leaf angle 1 (rla1), and cloned the corresponding gene. RLA1 was identical to the previously reported SMALL ORGAN SIZE 1 (SMOS1) which was cloned from another allele...
January 18, 2017: Plant Cell
https://www.readbyqxmd.com/read/28100624/azacytidine-treatment-inhibits-the-progression-of-herpes-stromal-keratitis-by-enhancing-regulatory-t-cell-function
#16
Siva Karthik Varanasi, Pradeep B J Reddy, Siddheshvar Bhela, Ujjaldeep Jaggi, Fernanda Gimenez, Barry T Rouse
: Ocular infection with Herpes Simplex Virus type 1 (HSV-1) sets off an inflammatory reaction in the cornea which leads to both virus clearance as well as chronic lesions that are orchestrated by CD4 T cells. Approaches that enhance the function of regulatory T cells (Treg) and dampen effector T cells can be effective to limit Stromal Keratitis (SK) lesion severity. In this report, we have explored the novel approach of inhibiting DNA methyltransferase activity using 5-Azacytidine (cytosine analog) to limit HSV-1 induced ocular lesions...
January 18, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28100602/find-tuberculosis-strain-bank-a-resource-for-researchers-and-developers-working-on-tests-to-detect-mycobacterium-tuberculosis-and-related-drug-resistance
#17
Belay Tessema, Pamela Nabeta, Eloise Valli, Audrey Albertini, Jimena Collantes, Nguyen Huu Lan, Elena Romancenco, Nestani Tukavdze, Claudia M Denkinger, David L Dolinger
BACKGROUND: The spread of multidrug-resistant tuberculosis and extensively drug-resistant TB hampers the global efforts in the fight against tuberculosis. To enhance the development and evaluation of diagnostic tests quickly and efficiently, well characterized strains and samples from drug resistant tuberculosis patients are necessary. In this project, FIND has focused on the collection, characterization and storage of such well-characterized reference materials and to make them available to researchers and developers...
January 18, 2017: Journal of Clinical Microbiology
https://www.readbyqxmd.com/read/28099939/type-5-phosphodiesterase-regulates-glioblastoma-multiforme-aggressiveness-and-clinical-outcome
#18
Valeriana Cesarini, Maurizio Martini, Lucia Ricci Vitiani, Giovanni Luca Gravina, Silvia Di Agostino, Grazia Graziani, Quintino Giorgio D'Alessandris, Roberto Pallini, Luigi M Larocca, Pellegrino Rossi, Emmanuele A Jannini, Susanna Dolci
Expression of type 5 phosphodiesterase (PDE5), a cGMP-specific hydrolytic enzyme, is frequently altered in human cancer, but its specific role in tumorigenesis remains controversial. Herein, by analyzing a cohort of 69 patients affected by glioblastoma multiforme (GBM) who underwent chemo- and radiotherapy after surgical resection of the tumor, we found that PDE5 was strongly expressed in cancer cells in about 50% of the patients. Retrospective analysis indicated that high PDE5 expression in GBM cells significantly correlated with longer overall survival of patients...
January 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28099528/inos-as-a-driver-of-inflammation-and-apoptosis-in-mouse-skeletal-muscle-after-burn-injury-possible-involvement-of-sirt1-s-nitrosylation-mediated-acetylation-of-p65-nf-%C3%AE%C2%BAb-and-p53
#19
Harumasa Nakazawa, Kyungho Chang, Shohei Shinozaki, Takashi Yasukawa, Kazuhiro Ishimaru, Shingo Yasuhara, Yong-Ming Yu, J A Jeevendra Martyn, Ronald G Tompkins, Kentaro Shimokado, Masao Kaneki
Inflammation and apoptosis develop in skeletal muscle after major trauma, including burn injury, and play a pivotal role in insulin resistance and muscle wasting. We and others have shown that inducible nitric oxide synthase (iNOS), a major mediator of inflammation, plays an important role in stress (e.g., burn)-induced insulin resistance. However, it remains to be determined how iNOS induces insulin resistance. Moreover, the interrelation between inflammatory response and apoptosis is poorly understood, although they often develop simultaneously...
2017: PloS One
https://www.readbyqxmd.com/read/28099441/puma-and-nf-kb-are-cell-signaling-predictors-of-reovirus-oncolysis-of-breast-cancer
#20
Chandini Thirukkumaran, Zhong-Qiao Shi, Ponnampalam Thirukkumaran, Joanne Luider, Karen Kopciuk, Jason Spurrell, Kate Elzinga, Don Morris
BACKGROUND AND PURPOSE: Reovirus is a ubiquitous RNA virus that exploits aberrant signaling pathways for its replication. The oncolytic potential of reovirus against numerous cancers under pre-clinical/clinical conditions has been documented by us and others. Despite its proven clinical activity, the underlying mechanisms of reovirus oncolysis is still not well elucidated. If reovirus therapy is to be optimized for cancer, including breast cancer patients, it is imperative to understand the mechanisms of reovirus oncolysis, especially in treatment of resistant tumour...
2017: PloS One
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