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https://www.readbyqxmd.com/read/29775873/psychosocial-stress-and-inflammation-driving-tryptophan-breakdown-in-children-and-adolescents-a-cross-sectional-analysis-of-two-cohorts
#1
Nathalie Michels, Gerard Clarke, Loreto Olavarria-Ramirez, Sonia Gómez-Martínez, Ligia Esperanza Díaz, Ascensión Marcos, Kurt Widhalm, Livia A Carvalho
BACKGROUND: Tryptophan breakdown is an important mechanism in several diseases e.g. inflammation and stress-induced inflammation have been associated with the development of depression via enhanced tryptophan breakdown. Depression is a major public health problem which commonly starts during adolescence, thus identifying underlying mechanisms during early life is crucial in prevention. The aim of this work was to verify whether independent and interacting associations of psychosocial stress and inflammation on tryptophan breakdown already exist in children and adolescents as a vulnerable age group...
May 15, 2018: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/29775752/the-genetics-and-molecular-pathogenesis-of-systemic-lupus-erythematosus-sle-in-populations-of-different-ancestry
#2
REVIEW
George N Goulielmos, Maria I Zervou, Vassilis M Vazgiourakis, Yogita Ghodke-Puranik, Alexandros Garyfallos, Timothy B Niewold
Systemic lupus erythematosus (SLE; OMIM 152700) is a highly heterogeneous disorder, characterized by differences in autoantibody profile, serum cytokines, and a multi-system involvement commonly affecting the skin, renal, musculoskeletal, and hematopoetic systems clinical manifestations involving. Disease features range from mild manifestations, such as rash or arthritis, to life-threatening end-organ manifestations, such as glomerulonephritis or thrombosis, and it is difficult to predict which manifestations will affect a given patient...
May 15, 2018: Gene
https://www.readbyqxmd.com/read/29775695/pulsatilla-decoction-inhibits-candida-albicans-proliferation-and-adhesion-in-a-mouse-model-of-vulvovaginal-candidiasis-via-the-dectin-1-signaling-pathway
#3
Lilin Yang, Haiwang Wu, Weiyu Qiu, Longyi Guo, Xin Du, Qingying Yu, Jie Gao, Songping Luo
ETHNOPHARMACOLOGICAL RELEVANCE: Pulsatilla decoction (PD) is a classical prescription in Traditional Chinese Medicine (TCM) and has been reported to have inhibitory effects on Candida albicans proliferation. STUDY AIM: To investigate the therapeutic effects of PD in the treatment of Vulvovaginal candidiasis (VVC) and elucidate the potential mechanism. MATERIALS AND METHODS: Female BALB/c mice (N=90) were randomized to six treatment groups, including the Control group, Model group, three PD groups and Fluconazole group which served as a positive control (20mg/kg weekly)...
May 15, 2018: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/29775480/titan-cells-formation-in-cryptococcus-neoformans-is-finely-tuned-by-environmental-conditions-and-modulated-by-positive-and-negative-genetic-regulators
#4
Benjamin Hommel, Liliane Mukaremera, Radames J B Cordero, Carolina Coelho, Christopher A Desjardins, Aude Sturny-Leclère, Guilhem Janbon, John R Perfect, James A Fraser, Arturo Casadevall, Christina A Cuomo, Françoise Dromer, Kirsten Nielsen, Alexandre Alanio
The pathogenic fungus Cryptococcus neoformans exhibits morphological changes in cell size during lung infection, producing both typical size 5 to 7 μm cells and large titan cells (> 10 μm and up to 100 μm). We found and optimized in vitro conditions that produce titan cells in order to identify the ancestry of titan cells, the environmental determinants, and the key gene regulators of titan cell formation. Titan cells generated in vitro harbor the main characteristics of titan cells produced in vivo including their large cell size (>10 μm), polyploidy with a single nucleus, large vacuole, dense capsule, and thick cell wall...
May 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29775310/fragment-based-discovery-of-a-potent-orally-bioavailable-inhibitor-which-modulates-the-phosphorylation-and-catalytic-activity-of-erk1-2
#5
Tom D Heightman, Valerio Berdini, Hannah Braithwaite, Ildiko Maria Buck, Megan Cassidy, Juan Castro, Aurelie Courtin, James E H Day, Charlotte East, Lynsey Fazal, Brent Graham, Charlotte M Griffiths-Jones, John F Lyons, Vanessa Martins, Sandra Muench, Joanne M Munck, David Norton, Marc O'Reilly, Nick Palmer, Puja Pathuri, Michael Reader, David C Rees, Sharna J Rich, Caroline Richardson, Harpreet Saini, Neil T Thompson, Nicola G Wallis, Hugh Walton, Nicola E Wilsher, Alison J-A Woolford, Michael Cooke, David Cousin, Stuart Onions, Jonathan Shannon, John Watts, Christopher W Murray
Aberrant activation of the MAPK pathway drives cell proliferation in multiple cancers. Inhibitors of BRAF and MEK kinases are approved for the treatment of BRAF mutant melanoma, but resistance frequently emerges, often mediated by increased signalling through ERK1/2. Here we describe the fragment based generation of ERK1/2 inhibitors which block catalytic phosphorylation of downstream substrates such as RSK but also modulate phosphorylation of ERK1/2 by MEK without directly inhibiting MEK. X-ray crystallographic and biophysical fragment screening followed by structure-guided optimization and growth from the hinge into a pocket proximal to the C-α helix afforded highly potent ERK1/2 inhibitors with excellent kinome selectivity...
May 18, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29775216/neuroimmflammation-and-microglia-in-glaucoma-time-for-a-paradigm-shift
#6
REVIEW
Xin Wei, Kin-Sang Cho, Eric F Thee, Martine J Jager, Dong Feng Chen
Glaucoma is a complex neurodegenerative disease with many clinical subtypes. Some of its rare forms include pigmentary glaucoma, uveitic glaucoma and congenital glaucoma. While they all share common features of progressive retinal ganglion cell (RGC) loss, optic nerve damage and corresponding visual field loss, the exact mechanisms underlying glaucomatous neuron loss are not clear. This has largely hindered the development of a real cure for this disease. Elevated intraocular pressure (IOP) is a known major risk factor of glaucoma; however, progressive degeneration of RGCs and axons can also be found in patients with a normal IOP, i...
May 18, 2018: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/29774792/hypofractionated-radiotherapy-is-superior-to-conventional-fractionation-in-an-orthotopic-model-of-anaplastic-thyroid-cancer
#7
Ayman J Oweida, Andy Phan, Benjamin Vancourt, Tyler Robin, Mohammad K Hararah, Shilpa Bhatia, Dallin Milner, Shelby Lennon, Laura Pike, David Raben, Bryan R Haugen, Nikita Pozdeyev, Rebecca E Schweppe, Sana D Karam
Anaplastic thyroid cancer is an aggressive and highly lethal disease with poor outcomes and resistance to therapy. Despite multimodality treatment including radiation therapy and chemotherapy, response rates remain below 15% with a median time to progression of less than 3 months. Recent advances in radiotherapy delivery and gene-expression profiling may help guide patient selection for personalized therapy. The purpose of this study was to characterize the response to radiation in a panel of ATC cell lines and to test alternative radiotherapy fractionation schedules for overcoming radioresistance...
May 18, 2018: Thyroid: Official Journal of the American Thyroid Association
https://www.readbyqxmd.com/read/29774782/the-neuroprotective-effect-of-ethanol-intoxication-in-tbi-is-associated-with-the-suppression-of-erbb-signaling-in-pv-positive-interneurons
#8
Akila Chandrasekar, Florian Olde Heuvel, Martin Wepler, Rida Rehman, Annette Palmer, Alberto Catanese, Birgit Linkus, Albert Ludolph, Tobias Boeckers, Markus Huber-Lang, Peter Radermacher, Francesco Roselli
Ethanol intoxication (EI) is a frequent comorbidity of TBI, but the impact of EI on TBI pathogenic cascades and prognosis is unclear: although clinical evidence suggests that EI may have neuroprotective effects, experimental support is, to date, inconclusive. We aimed at elucidating the impact of EI on TBI-associated neurological deficits, signaling pathways and pathogenic cascades, in order to identify new modifiers of TBI pathophysiology. We have shown that ethanol administration (5g/Kg) before trauma enhances behavioral recovery in a weight-drop TBI model; neuronal survival in the injured somatosensory cortex was enhanced by EI...
May 18, 2018: Journal of Neurotrauma
https://www.readbyqxmd.com/read/29774579/integrative-epigenetic-analysis-reveals-therapeutic-targets-to-the-dna-methyltransferase-inhibitor-sgi-110-in-hepatocellular-carcinoma
#9
Minmin Liu, Lian Zhang, Hongtao Li, Toshinori Hinoue, Wanding Zhou, Hitoshi Ohtani, Anthony El-Khoueiry, John Daniels, Casey O'Connell, Tanya B Dorff, Qianjin Lu, Daniel J Weisenberger, Gangning Liang
There is an urgent need for developing more effective therapies for hepatocellular carcinoma (HCC) because of its aggressiveness. Guadecitabine (SGI-110) is a second-generation DNA methyltransferase inhibitor (DNMTi) currently in clinical trials for HCC and shows greater stability and performance over first generation DNMTis. In order to identify potential therapeutic targets of SGI-110 for clinical trials, HCC cell lines (SNU398, HepG2 and SNU475) were used to evaluate effects of transient SGI-110 treatment by an integrative analysis of DNA methylation, nucleosome accessibility, gene expression profiles and its clinical relevance by comparisons to TCGA HCC clinical data...
May 18, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29774576/spatial-vision-in-older-adults-perceptual-changes-and-neural-bases
#10
REVIEW
Allison M McKendrick, Yu Man Chan, Bao N Nguyen
PURPOSE: The number of older adults is rapidly increasing internationally, leading to a significant increase in research on how healthy ageing impacts vision. Most clinical assessments of spatial vision involve simple detection (letter acuity, grating contrast sensitivity, perimetry). However, most natural visual environments are more spatially complicated, requiring contrast discrimination, and the delineation of object boundaries and contours, which are typically present on non-uniform backgrounds...
May 17, 2018: Ophthalmic & Physiological Optics: the Journal of the British College of Ophthalmic Opticians (Optometrists)
https://www.readbyqxmd.com/read/29774529/inhibition-of-prmt3-activity-selectively-impairs-lxr-driven-transcription-of-hepatic-lipogenic-genes-in-vivo
#11
Joya E Nahon, Christianne Groeneveldt, Janine J Geerling, Miranda Van Eck, Menno Hoekstra
BACKGROUND AND PURPOSE: Agonists for the liver X receptor (LXR) are considered promising therapeutic moieties in cholesterol-driven diseases by promoting cellular cholesterol efflux pathways. However, current clinical application of these agents is hampered by the concomitant LXR-induced activation of a lipogenic transcriptional network, leading to hepatic steatosis. Recent studies have suggested that protein arginine methyltransferase 3 (PRMT3) may act as a selective co-activator of LXR activity...
May 18, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29774498/microrna-1231-exerts-a-tumor-suppressor-role-through-regulating-the-egfr-pi3k-akt-axis-in-glioma
#12
Jiale Zhang, Jie Zhang, Wenjin Qiu, Jian Zhang, Yangyang Li, Enjun Kong, Ailin Lu, Jia Xu, Xiaoming Lu
PURPOSE: MicroRNAs (miRNAs) have been shown to be involved in the initiation and progression of glioma. However, the underlying molecular mechanisms are still unclear. METHODS: We performed microarray analysis to evaluate miRNA expression levels in 158 glioma tissue samples, and examined miR-1231 levels in glioma samples and healthy brain tissues using qRT-PCR. In vitro analyses were performed using miR-1231 mimics, inhibitors, and siRNA targeting EGFR. We used flow cytometry, CCK-8 assays, and colony formation assays to examine glioma proliferation and cell cycle analysis...
May 17, 2018: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29774490/higher-activation-of-the-interferon-gamma-signaling-pathway-in-systemic-lupus-erythematosus-patients-with-a-high-type-i-ifn-score-relation-to-disease-activity
#13
Manman Liu, Junli Liu, Shumeng Hao, Ping Wu, Xiaoyan Zhang, Yichuan Xiao, Gengru Jiang, Xinfang Huang
Increased IFN-γ levels have been associated with systemic lupus erythematosus (SLE). However, the relationships among IFN-γ, type I interferons (IFNs) and clinical features have not been extensively studied. Peripheral blood samples from 44 SLE patients and 36 healthy donors (HDs) were collected. Quantitative real-time PCR was used to assess the mRNA expression of IFNG, type II IFN-inducible genes (IRF1, GBP1, CXCL9, CXCL10, and SERPING1, which are used for the type II IFN score), type I IFN-inducible genes (IRF7, MX1, ISG15, and ISG20, which are used for the type I IFN score), TBX21, and EOMES in peripheral blood mononuclear cells...
May 17, 2018: Clinical Rheumatology
https://www.readbyqxmd.com/read/29774176/pushing-the-limits-machine-preservation-of-the-liver-as-a-tool-to-recondition-high-risk-grafts
#14
REVIEW
Yuri L Boteon, Simon C Afford, Hynek Mergental
Purpose of the Review: Machine perfusion (MP) is a novel technology recently introduced in liver transplantation, redefining the current practice of organ preservation and pushing the limits of high-risk liver utilisation. This review highlights the key benefits of machine perfusion over conventional static cold storage (SCS), demonstrated in human liver research and clinical transplants. Recent Findings: The first clinical trials have demonstrated both safety and feasibility of MP...
2018: Current Transplantation Reports
https://www.readbyqxmd.com/read/29774133/sporadic-renal-angiomyolipoma-in-a-patient-with-birt-hogg-dub%C3%A3-chaperones-in-pathogenesis
#15
Rebecca A Sager, Mark R Woodford, Oleg Shapiro, Mehdi Mollapour, Gennady Bratslavsky
Birt-Hogg-Dubé (BHD) is an autosomal dominant genetic syndrome caused by germline mutations in the FLCN gene that predisposes patients to develop renal tumors. Renal angiomyolipoma (AML) is not a renal tumor sub-type associated with BHD. AML is, however, a common phenotypic manifestation of Tuberous Sclerosis Complex (TSC) syndrome caused by mutations in either the TSC1 or TSC2 tumor suppressor genes. Previous case reports of renal AML in patients with BHD have speculated on the molecular and clinical overlap of these two syndromes as a result of described involvement of the gene products in the mTOR pathway...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29774132/natural-products-a-hope-for-glioblastoma-patients
#16
REVIEW
Raghupathy Vengoji, Muzafar A Macha, Surinder K Batra, Nicole A Shonka
Glioblastoma (GBM) is one of the most aggressive malignant tumors with an overall dismal survival averaging one year despite multimodality therapeutic interventions including surgery, radiotherapy and concomitant and adjuvant chemotherapy. Few drugs are FDA approved for GBM, and the addition of temozolomide (TMZ) to standard therapy increases the median survival by only 2.5 months. Targeted therapy appeared promising in in vitro monolayer cultures, but disappointed in preclinical and clinical trials, partly due to the poor penetration of drugs through the blood brain barrier (BBB)...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29774105/pre-clinical-activity-of-targeting-the-pi3k-akt-mtor-pathway-in-burkitt-lymphoma
#17
Maria Bhatti, Thomas Ippolito, Cory Mavis, Juan Gu, Mitchell S Cairo, Megan S Lim, Francisco Hernandez-Ilizaliturri, Matthew J Barth
Though outcomes for pediatric Burkitt lymphoma (BL) have improved significantly in recent decades with intensive multi-agent chemotherapy and the addition of rituximab, chemotherapy resistance remains a significant impediment to cure following relapse. Activation of the PI3K/AKT pathway has been implicated in Burkitt lymphomagenesis and increased PI3K/AKT activation has been associated with worse outcomes in adults with aggressive B-cell non-Hodgkin lymphoma (B-NHL). Inhibitors of the PI3K/AKT pathway have been approved for the treatment of refractory indolent B-NHL and continue to be investigated for treatment of aggressive B-NHLs...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29774101/qilin-pills-alleviate-oligoasthenospermia-by-inhibiting-bax-caspase-9-apoptosis-pathway-in-the-testes-of-model-rats
#18
Kaishu Zhang, Zhengyan Ge, Longlong Fu, Qi An, Fang Zhou, Ying Guo, Xiaowei Wang, Wenhong Lu, Xiaowei Liang, Shusong Wang, Xuejun Shang, Yiqun Gu
At present, the treatment of oligoasthenospermia with western medicine is ineffective. Qilin pill (QLP) is a Chinese traditional medicine for treating male infertility. Recent multicenter clinical studies in China reported that QLPs markedly improved sperm quality. However, the mechanism of action of QLPs on oligoasthenospermia remains unknown. In this study, we investigated the mechanistic basis for improvement of semen parameters and reversal of testis damage by QLPs in a rat model of oligoasthenospermia induced by treatment with tripterygium glycosides (TGs) (40 mg/kg) once daily for 4 weeks...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29774079/long-non-coding-rnas-ac026904-1-and-uca1-a-one-two-punch-for-tgf-%C3%AE-induced-snai2-activation-and-epithelial-mesenchymal-transition-in-breast-cancer
#19
Guo-Yin Li, Wei Wang, Jian-Yong Sun, Bo Xin, Xiang Zhang, Ting Wang, Qian-Feng Zhang, Li-Bo Yao, Hua Han, Dai-Ming Fan, An-Gang Yang, Lin-Tao Jia, Lei Wang
Transforming growth factor-β (TGF-β) has received much attention as a major inducer of epithelial-mesenchymal transition (EMT) during cancer progression, mainly by activating a set of pleiotropic transcription factors including SNAI2/Slug. However, the involvement of long non-coding RNAs (lncRNAs) in TGF-β-induced Slug activation and EMT remains largely unknown. Methods: In this study, we used microarray analysis to compare lncRNA expression profiles between TGF-β treated and untreated breast cancer cells...
2018: Theranostics
https://www.readbyqxmd.com/read/29774072/twist-promotes-tumor-metastasis-in-basal-like-breast-cancer-by-transcriptionally-upregulating-ror1
#20
Jingying Cao, Xin Wang, Tao Dai, Yuanzhong Wu, Meifang Zhang, Renxian Cao, Ruhua Zhang, Gang Wang, Rou Jiang, Binhua P Zhou, Jian Shi, Tiebang Kang
Rationale: Twist is a key transcription factor for induction of epithelial-mesenchymal transition (EMT), which promotes cell migration, invasion, and cancer metastasis, confers cancer cells with stem cell-like characteristics, and provides therapeutic resistance. However, the functional roles and targeted genes of Twist in EMT and cancer progression remain elusive. Methods: The potential targeted genes of Twist were identified from the global transcriptomes of T47D/Twist cells by microarray analysis. EMT phenotype was detected by western blotting and immunofluorescence of marker proteins...
2018: Theranostics
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