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https://www.readbyqxmd.com/read/29471449/obesity-associated-advanced-glycation-end-products-within-the-human-uterine-cavity-adversely-impact-endometrial-function-and-embryo-implantation-competence
#1
Gabriella S Antoniotti, Melinda Coughlan, Lois A Salamonsen, Jemma Evans
STUDY QUESTION: Do obese levels of advanced glycation end products (AGEs) within the uterine cavity detrimentally alter tissue function in embryo implantation and placental development? SUMMARY ANSWER: Obese levels of AGEs activate inflammatory signaling (p65 NFκB) within endometrial epithelial cells and alter their function, cause endoplasmic reticulum (ER) stress in endometrial stromal cells and impair decidualization, compromise implantation of blastocyst mimics and inhibit trophoblast invasion...
February 20, 2018: Human Reproduction
https://www.readbyqxmd.com/read/29454579/nucleus-accumbens-inflammation-mediates-anxiodepressive-behavior-and-compulsive-sucrose-seeking-elicited-by-saturated-dietary-fat
#2
Léa Décarie-Spain, Sandeep Sharma, Cécile Hryhorczuk, Victor Issa Garcia, Philip A Barker, Nathalie Arbour, Thierry Alquier, Stephanie Fulton
OBJECTIVE: The incidence of depression is significantly compounded by obesity. Obesity arising from excessive intake of high-fat food provokes anxiodepressive behavior and elicits molecular adaptations in the nucleus accumbens (NAc), a region well-implicated in the hedonic deficits associated with depression and in the control of food-motivated behavior. To determine the etiology of diet-induced depression, we studied the impact of different dietary lipids on anxiodepressive behavior and metabolic and immune outcomes and the contribution of NAc immune activity...
January 31, 2018: Molecular Metabolism
https://www.readbyqxmd.com/read/29435148/peptide-inhibition-of-the-setd6-methyltransferase-catalytic-activity
#3
Michal Feldman, Dan Levy
A large body of evidence accumulating in the past few years indicates the physiological significance of non-histone proteins lysine methylation, catalyzed by protein lysine methyl transferases (PKMTs). Dysregulation of these enzymes was shown to contribute to the development and progression of numerous diseases. SETD6 lysine methylatransferase was recently shown to participate in essential cellular processes, such as the NFkB pathway, oxidative stress and also the Wnt signaling cascade. In order to test the effect of blocking SETD6 catalytic activity, we used the peptide inhibition method, which is considered highly specific and can potentially target almost any protein...
January 12, 2018: Oncotarget
https://www.readbyqxmd.com/read/29416696/tnfr-tnf-%C3%AE-signaling-pathway-regulates-apoptosis-of-alveolar-macrophages-in-coal-workers-pneumoconiosis
#4
Qing-Zeng Qian, Xiang-Ke Cao, Hai-Yan Liu, Guo-Ying Zheng, Qing-Qiang Qian, Fu-Hai Shen
We explored the role of TNFR/TNF-α signalingin apoptosis among alveolar macrophages (AM) and its relevance to the development of coal workers' pneumoconiosis (CWP). Purified alveolar macrophages (AMs) were prepared from bronchoalveolar lavage fluid harvested from 366 CWP patients and 120 healthy subjects enrolled inthe study. The purified AMs were then divided into control, SOD, anti-TNFR, TNFR and NFkB inhibitor groups and analyzed for apoptosis usingflow cytometry (sub-diploid peak) and western blotting (Bcl-2, Caspase-3 and Caspase-8 expression)...
January 2, 2018: Oncotarget
https://www.readbyqxmd.com/read/29416668/molecular-mechanisms-of-cardioprotective-effects-mediated-by-transplanted-cardiac-ckit-cells-through-the-activation-of-an-inflammatory-hypoxia-dependent-reparative-response
#5
Giovanni Puddighinu, Domenico D'Amario, Eleonora Foglio, Melissa Manchi, Andrea Siracusano, Elena Pontemezzo, Martina Cordella, Francesco Facchiano, Laura Pellegrini, Antonella Mangoni, Marco Tafani, Filippo Crea, Antonia Germani, Matteo Antonio Russo, Federica Limana
The regenerative effects of cardiac ckit+ stem cells (ckit+CSCs) in acute myocardial infarction (MI) have been studied extensively, but how these cells exert a protective effect on cardiomyocytes is not well known. Growing evidences suggest that in adult stem cells injury triggers inflammatory signaling pathways which control tissue repair and regeneration. Aim of the present study was to determine the mechanisms underlying the cardioprotective effects of ckit+CSCs following transplantation in a murine model of MI...
January 2, 2018: Oncotarget
https://www.readbyqxmd.com/read/29415184/nlrp3-gene-expression-in-circulating-leukocytes-declines-during-healthy-aging
#6
Jean-Louis Connat, Adélie Dumont, Mickaël Rialland, Bruno Faivre, Gabriele Sorci
Aging is often associated with elevated levels of low grade inflammation supposed to drive age-associated diseases. Here, we conducted a cross-sectional study on 58 healthy volunteers, aged from 19 to 81, to investigate the relationship between age and the expression of three inflammasome component genes (Nlrp3, Asc, Casp1), the up-stream transcription factor NFkB, and the pro-inflammatory cytokine Il-1 in leukocytes. We also assessed C-reactive protein (CRP) and IL-1 in plasma, as additional inflammatory markers...
February 3, 2018: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/29411932/screening-for-selective-protein-inhibitors-using-ianus-peptide-array
#7
Frank Erdmann, Erik Prell, Günther Jahreis, Gunter Fischer, Miroslav Malesevic
The IANUS (Induced orgANization of strUcture by matrix-assisted togethernesS) peptide array was build up on a hypothesis that two peptides from two interacting protein epitopes are also able to interact when immobilized on a solid support. This peptide-peptide interactions can be visualized by FRET effects caused by close proximity of fluorescent labeled peptide chains. The biggest advantage of this low-resolution method is that no soluble protein probe or selective antibodies are needed. We applied the IANUS peptide array to screen for peptides from a phospatase Calcineurin (CaN) that binds to regulatory domain of the nuclear factor of activated T cells (NFAT)...
February 7, 2018: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/29405541/structural-diversity-and-anticancer-activity-of-marine-derived-elastase-inhibitors-key-features-and-mechanisms-mediating-the-antimetastatic-effects-in-invasive-breast-cancer
#8
Fatma H Al-Awadhi, Valerie J Paul, Hendrik Luesch
Three new 3-amino-6-hydroxy-2-piperidone (Ahp)-containing cyclic depsipeptides named loggerpeptins A-C (1-3) along with molassamide (4) were discovered from a marine cyanobacterium, extending the structural diversity of this prevalent scaffold of cyanobacterial serine protease inhibitors. Molassamide (4), containing the 2-amino-butenoic (Abu) unit in the cyclic core, was the most potent and selective analogue against human neutrophil elastase (HNE). Given the growing evidence supporting the role of HNE in breast cancer progression and metastasis, we assessed the cellular effects of compounds 3 and 4 in the context of targeting invasive breast cancer...
February 5, 2018: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/29384411/mass-spectrometry-analysis-of-plasma-from-amyotrophic-lateral-sclerosis-and-control-subjects
#9
Zhouwei Xu, Aven Lee, Amanda Nouwens, Robert David Henderson, Pamela Ann Mccombe
Mass spectrometry was used to study blood samples from patients with amyotrophic lateral sclerosis (ALS) and healthy controls. Addenbrooke's cognitive examination-III (ACE-III) was used to test for cognitive impairment (CI). Nano liquid chromatography and time of flight mass spectrometry (MS) were performed on samples from 42 ALS patients and 18 healthy controls. SWATH™ proteomic analysis was utilized to look for differences between groups. Western blot analysis was used to study levels of 4 proteins, selected as being of possible interest in ALS, in the MS discovery cohort and a second validation group of 10 ALS patients and 10 healthy controls...
January 31, 2018: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration
https://www.readbyqxmd.com/read/29376464/the-flavonoid-2-methoxy-6-methylflavone-affords-neuroprotection-following-focal-cerebral-ischaemia
#10
Andrew N Clarkson, Lily Boothman-Burrell, Zita Dósa, Raghavendra Y Nagaraja, Liang Jin, Kim Parker, Petra S van Nieuwenhuijzen, Silke Neumann, Emma K Gowing, Navnath Gavande, Philip K Ahring, Mai M Holm, Jane R Hanrahan, Joseph A Nicolazzo, Kimmo Jensen, Mary Chebib
Tonic inhibitory currents, mediated by extrasynaptic GABAA receptors, are elevated at a delay following stroke. Flavonoids minimise the extent of cellular damage following stroke, but little is known about their mode of action. We demonstrate that the flavonoid, 2'-methoxy-6-methylflavone (0.1-10 µM; 2'MeO6MF), increases GABAA receptor tonic currents presumably via δ-containing GABAA receptors. Treatment with 2'MeO6MF 1-6 h post focal ischaemia dose dependently decreases infarct volume and improves functional recovery...
January 1, 2018: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/29354850/c11orf95-rela-fusions-and-upregulated-nf-kb-signalling-characterise-a-subset-of-aggressive-supratentorial-ependymomas-that-express-l1cam-and-nestin
#11
Prit Benny Malgulwar, Aruna Nambirajan, Pankaj Pathak, Mohammed Faruq, Madhu Rajeshwari, Manmohan Singh, Vaishali Suri, Chitra Sarkar, Mehar Chand Sharma
Ependymomas (EPN) show site specific genetic alterations and a recent DNA methylation profiling study identified nine molecular subgroups. C11orf95-RELA and YAP1 fusions characterise the RELA and YAP1 molecular subgroups, respectively, of supratentorial (ST)-EPNs. Current guidelines recommend molecular subgrouping over histological grade for accurate prognostication. Clinicopathological features of ST-EPNs in correlation with C11orf95-RELA and YAP1 fusions have been assessed in only few studies. We aimed to study these fusions in EPNs, and identify diagnostic and prognostic markers...
January 22, 2018: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29340039/integrative-molecular-network-analysis-identifies-emergent-enzalutamide-resistance-mechanisms-in-prostate-cancer
#12
Carly J King, Josha Woodward, Jacob Schwartzman, Daniel J Coleman, Robert Lisac, Nicholas J Wang, Kathryn Van Hook, Lina Gao, Joshua Urrutia, Mark A Dane, Laura M Heiser, Joshi J Alumkal
Recent work demonstrates that castration-resistant prostate cancer (CRPC) tumors harbor countless genomic aberrations that control many hallmarks of cancer. While some specific mutations in CRPC may be actionable, many others are not. We hypothesized that genomic aberrations in cancer may operate in concert to promote drug resistance and tumor progression, and that organization of these genomic aberrations into therapeutically targetable pathways may improve our ability to treat CRPC. To identify the molecular underpinnings of enzalutamide-resistant CRPC, we performed transcriptional and copy number profiling studies using paired enzalutamide-sensitive and resistant LNCaP prostate cancer cell lines...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29322004/thoughts-modulate-the-expression-of-inflammatory-genes-and-may-improve-the-coronary-blood-flow-in-patients-after-a-myocardial-infarction
#13
Carlo Dal Lin, Mariela Marinova, Giorgio Rubino, Elisabetta Gola, Alessandra Brocca, Giorgia Pantano, Laura Brugnolo, Cristiano Sarais, Umberto Cucchini, Biancarosa Volpe, Chiara Cavalli, Maura Bellio, Emilia Fiorello, Sofia Scali, Mario Plebani, Sabino Iliceto, Francesco Tona
Background: Mental stress is one of the main risk factors for cardiovascular disease. Meditation and music listening are two techniques that are able to counteract it through the activation of specific brain areas, eliciting the so-called Relaxing Response (RR). Epidemiological evidence reveals that the RR practice has a beneficial prognostic impact on patients after myocardial infarction. We aimed to study the possible molecular mechanisms of RR underlying these findings. Methods: We enrolled 30 consecutive patients after myocardial infarction and 10 healthy controls...
January 2018: Journal of Traditional and Complementary Medicine
https://www.readbyqxmd.com/read/29309990/ex-vivo-generation-of-drug-eluting-islets-improves-transplant-outcomes-by-inhibiting-tlr4-mediated-nfkb-upregulation
#14
Charles A Chang, Babatope Akinbobuyi, Jeremy M Quintana, Gumpei Yoshimatsu, Bashoo Naziruddin, Robert R Kane
The systemic administration of immunosuppressive and anti-inflammatory drugs is routinely employed in organ transplantation to minimize graft rejection and improve graft survival. Localized drug delivery has the potential to improve transplant outcomes by providing sustained exposure to efficacious drug concentrations while avoiding systemic immunosuppression and off-target effects. Here, we describe the synthesis of a novel prodrug and its direct covalent conjugation to pancreatic islets via a cleavable linker...
December 28, 2017: Biomaterials
https://www.readbyqxmd.com/read/29301753/exosomes-associated-with-human-ovarian-tumors-harbor-a-reversible-checkpoint-of-t-cell-responses
#15
Gautam N Shenoy, Jenni L Loyall, Orla Maguire, Vandana Iyer, Raymond J Kelleher, Hans Minderman, Paul K Wallace, Kunle Odunsi, Sathy V Balu-Iyer, Richard B Bankert
Nano-sized membrane-encapsulated extracellular vesicles isolated from the ascites fluids of ovarian cancer patients are identified as exosomes based on their biophysical and compositional characteristics. We report here that T cells pulsed with these tumor-associated exosomes during TCR-dependent activation inhibit various activation endpoints including translocation of NFkB and NFAT into the nucleus, upregulation of CD69 and CD107a, production of cytokines and cell proliferation. Additionally, the activation of virus-specific CD8+ T cells that are stimulated with the cognate viral peptides presented in the context of class I MHC is also suppressed by the exosomes...
January 4, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29296837/baseline-mutational-patterns-and-sustained-mrd-negativity-in-patients-with-high-risk-smoldering-myeloma
#16
Sham Mailankody, Dickran Kazandjian, Neha Korde, Mark Roschewski, Elisabet Manasanch, Manisha Bhutani, Nishant Tageja, Mary Kwok, Yong Zhang, Adriana Zingone, Laurence Lamy, Rene Costello, Candis Morrison, Malin Hultcrantz, Austin Christofferson, Megan Washington, Martin Boateng, Seth M Steinberg, Maryalice Stetler-Stevenson, William D Figg, Elli Papaemmanuil, Wyndham H Wilson, Jonathan J Keats, Ola Landgren
Early results of a prospective phase 2 clinical trial of carfilzomib, lenalidomide, and dexamethasone followed by lenalidomide maintenance in high-risk smoldering myeloma showed promising results that were previously published. Here, we provide novel insights into the genetic landscape of high-risk smoldering myeloma and information on sustained minimal residual disease (MRD) negativity with an expanded cohort of patients. Eighteen patients with high-risk smoldering myeloma were enrolled between 29 May 2012, and 14 January 2014...
October 10, 2017: Blood Advances
https://www.readbyqxmd.com/read/29287594/comprehensive-molecular-biomarker-identification-in-breast-cancer-brain-metastases
#17
Hans-Juergen Schulten, Mohammed Bangash, Sajjad Karim, Ashraf Dallol, Deema Hussein, Adnan Merdad, Fatma K Al-Thoubaity, Jaudah Al-Maghrabi, Awatif Jamal, Fahad Al-Ghamdi, Hani Choudhry, Saleh S Baeesa, Adeel G Chaudhary, Mohammed H Al-Qahtani
BACKGROUND: Breast cancer brain metastases (BCBM) develop in about 20-30% of breast cancer (BC) patients. BCBM are associated with dismal prognosis not at least due to lack of valuable molecular therapeutic targets. The aim of the study was to identify new molecular biomarkers and targets in BCBM by using complementary state-of-the-art techniques. METHODS: We compared array expression profiles of three BCBM with 16 non-brain metastatic BC and 16 primary brain tumors (prBT) using a false discovery rate (FDR) p < 0...
December 29, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29278644/endothelial-cells-of-extremely-premature-infants-display-impaired-immune-response-after-proinflammatory-stimulation
#18
Lukas Wisgrill, Martina Muck, Isabelle Wessely, Angelika Berger, Andreas Spittler, Elisabeth Förster-Waldl, Kambis Sadeghi
BACKGROUND: Endothelial cells (ECs) exert immunological functions such as production of proinflammatory cytokines/chemokines as well as facilitation of extravasation of immune cells into infected tissue. Limited data are available on the functionality of ECs from extremely preterm neonates during infection. Accordingly, the aim of our study was to investigate the immune response of premature ECs after proinflammatory stimulation. METHODS: Cell adhesion receptors expression and function, NFkB-signaling and chemokine production were analyzed in umbilical cord ECs from extremely preterm and term neonates after proinflammatory stimulation...
August 21, 2017: Pediatric Research
https://www.readbyqxmd.com/read/29277983/thymoquinone-can-improve-neuronal-survival-and-promote-neurogenesis-in-rat-hippocampal-neurons
#19
Merve Beker, Tuğçe Dallı, Birsen Elibol
SCOPE: Thymoquinone (TQ) has been used as a potential therapeutic for diseases such as cancer, and diabetes. Herein, we aimed to investigate the effect of TQ on behavioral and molecular parameters in healthy rat hippocampus. METHODS: TQ (20 mg/kg/day) was administered intragastrically for 15 days to adult rats. After the behavioral tests, the hippocampal tissues were investigated in histological and molecular level. RESULTS: In both DG and CA1, TQ significantly increased the number of hippocampal neurons...
December 26, 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/29260979/hspa5-negatively-regulates-lysosomal-activity-through-ubiquitination-of-mul1-in-head-and-neck-cancer
#20
Sun-Yong Kim, Hyo Jeong Kim, Haeng-Jun Kim, Dae Ho Kim, Chul-Ho Kim, Jae Ho Han, Hyung Kwon Byeon, Keunho Lee
HSPA5/GRP78/BiP plays an important role in cell survival or tumor progression. For these reasons, HSPA5 is an emerging therapeutic target in cancer development. Here we report that HSPA5 contributes to head and neck cancer (HNC) survival via maintenance of lysosomal activity; however, a nonthermal plasma (NTP, considered as a next-generation cancer therapy)-treated solution (NTS) inhibits HNC progression through HSPA5-dependent alteration of lysosomal activity. HSPA5 prevents NTS-induced lysosome inhibition through lysosomal-related proteins or regulation of gene expression...
December 20, 2017: Autophagy
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