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https://www.readbyqxmd.com/read/29917052/nrf2-deficiency-impairs-atherosclerotic-lesion-development-but-promotes-features-of-plaque-instability-in-hypercholesterolemic-mice
#1
Anna-Kaisa Ruotsalainen, Jari P Lappalainen, Emmi Heiskanen, Mari Merentie, Virve Sihvola, Juha Näpänkangas, Line Lottonen-Raikaslehto, Emilia Kansanen, Simone Adinolfi, Kai Kaarniranta, Seppo Ylä-Herttuala, Matti Jauhiainen, Eija Pirinen, Anna-Liisa Levonen
Aims: Oxidative stress and inflammation play an important role in the progression of atherosclerosis. Transcription factor NF-E2-related factor 2 (Nrf2) has antioxidant and anti-inflammatory effects in the vessel wall, but paradoxically, global loss of Nrf2 in apoE deficient mice alleviates atherosclerosis. In this study, we investigated the effect of global Nrf2 deficiency on early and advanced atherogenesis in alternative models of atherosclerosis, LDL receptor deficient mice (LDLR-/-) and LDLR-/- mice expressing apoB-100 only (LDLR-/-ApoB100/100) having a humanized lipoprotein profile...
June 18, 2018: Cardiovascular Research
https://www.readbyqxmd.com/read/29917003/sacubitril-valsartan-from-a-large-clinical-trial-to-clinical-practice
#2
Edoardo Sciatti, Michele Senni, Carlo M Lombardi, Mauro Gori, Marco Metra
: The Prospective Comparison of Angiotensin Receptor Antagonist and Neprilysin Inhibitor with Angiotensin-Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure Trial has shown a reduction in the risk of death and heart failure hospitalizations with sacubitril/valsartan, compared with enalapril, in patients with heart failure and reduced ejection fraction. Guidelines now recommend the substitution of angiotensin-converting enzyme inhibitors or AT1 blockers with sacubitril/valsartan in patients with heart failure and reduced ejection fraction...
June 16, 2018: Journal of Cardiovascular Medicine
https://www.readbyqxmd.com/read/29916142/lipotoxic-effects-of-palmitic-acid-on-astrocytes-are-associated-with-autophagy-impairment
#3
Ana Ortiz-Rodriguez, Estefania Acaz-Fonseca, Patricia Boya, Maria Angeles Arevalo, Luis M Garcia-Segura
Obesity is associated with an increase in the brain levels of saturated free fatty acids, such as palmitic acid (PA). Previous studies have shown that PA exerts proinflammatory actions and reduces cell viability in astrocyte cultures. In this study, we have assessed whether an alteration in autophagy is involved in the effects of PA on astrocytes. Primary astrocytes were obtained from the cerebral cortex of male and female CD1 mouse pups and were incubated for 4.5 or 24 h with 250-500 μM PA. PA increased the levels of LC3-II, an autophagosome marker, and reduced LC3-II flux in astrocytes, suggesting a blockade of autophagy...
June 18, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29916141/arginylated-calreticulin-increases-apoptotic-response-induced-by-bortezomib-in-glioma-cells
#4
Andrea Comba, Laura V Bonnet, Victor E Goitea, Marta E Hallak, Mauricio R Galiano
After retrotranslocation from the endoplasmic reticulum to the cytoplasm, calreticulin is modified by the enzyme arginyltransferase-1 (ATE1). Cellular levels of arginylated calreticulin (R-CRT) are regulated in part by the proteasomal system. Under various stress conditions, R-CRT becomes associated with stress granules (SGs) or reaches the plasma membrane (PM), where it participates in pro-apoptotic signaling. The mechanisms underlying the resistance of tumor cells to apoptosis induced by specific drugs remain unclear...
June 18, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29915948/thyroid-hormone-receptor-beta-1-expression-in-early-breast-cancer-a-validation-study
#5
K J Jerzak, J G Cockburn, S K Dhesy-Thind, G R Pond, K I Pritchard, S Nofech-Mozes, P Sun, S A Narod, A Bane
PURPOSE: Preliminary data suggest that high expression of the TRβ1 tumor suppressor is associated with longer survival among women with early breast cancer. We undertook this study to validate these findings. METHODS: In this prospective cohort study, we analyzed the prognostic significance of TRβ1 protein expression in the breast tumors of 796 women who had undergone breast surgery in the Henrietta Banting Breast Cancer database. All women were recruited after undergoing primary surgical therapy at Women's College Hospital (Toronto, ON, Canada) between January 1987 and December 2000...
June 18, 2018: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/29915896/targeting-egfr-in-lung-cancer-current-standards-and-developments
#6
REVIEW
Asunción Díaz-Serrano, Pablo Gella, Elisabeth Jiménez, Jon Zugazagoitia, Luis Paz-Ares Rodríguez
Lung cancer is the second most common malignant tumor and the leading cause of cancer death. Epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) is a distinct subtype of lung cancer comprising approximately 15-40% of non-squamous tumors. The development of first- and second-generation EGFR tyrosine kinase inhibitors (TKIs) has been a significant step forward in the treatment of patients with EGFR-mutant tumors, and over the last few years has been the therapy of choice in the initial management of patients with activating mutations in EGFR, with some differences in efficacy and toxicity profile...
June 18, 2018: Drugs
https://www.readbyqxmd.com/read/29915882/androgen-receptor-and-ki67-expression-and-survival-outcomes-in-non-small-cell-lung-cancer
#7
Laurel Grant, Shantanu Banerji, Leigh Murphy, David E Dawe, Craig Harlos, Yvonne Myal, Zoann Nugent, Anne Blanchard, Carla R Penner, Gefei Qing, Marshall W Pitz
Lung cancer is the most common cause of cancer-related deaths worldwide with non-small cell lung cancer (NSCLC) making up most of these cases. Males have poorer overall survival compared to women following a lung cancer diagnosis. Many studies have focused on the effects of estrogen to explain higher survival rates among women, but few have looked at the effects of androgens. We describe the expression of the androgen receptor (AR) and Ki67 in lung cancer specimens in the Manitoba Tumor Bank (MTB) and correlate these factors with patient outcome...
June 18, 2018: Hormones & Cancer
https://www.readbyqxmd.com/read/29915579/cytokine-secretion-and-pyroptosis-of-thyroid-follicular-cells-mediated-by-enhanced-nlrp3-nlrp1-nlrc4-and-aim2-inflammasomes-are-associated-with-autoimmune-thyroiditis
#8
Qingling Guo, Ying Wu, Yuanyuan Hou, Yongping Liu, Tingting Liu, Hao Zhang, Chenling Fan, Haixia Guan, Yushu Li, Zhongyan Shan, Weiping Teng
Background: Inflammasomes, which mediate maturation of interleukin-1β (IL-β) and interleukin-18 (IL-18) and lead to pyroptosis, have been linked to various autoimmune disorders. This study investigated whether they are involved in the pathogenesis of autoimmune thyroiditis (AIT). Methods: We collected thyroid tissues from 50 patients with AIT and 50 sex- and age-matched controls. Serum levels of free T3, free T4, thyrotropin, thyroid peroxidase antibody (TPOAb), and thyroglobulin antibody (TgAb) were measured by electrochemiluminescent immunoassays...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29914540/cooperation-of-pd-1-and-lag-3-in-the-exhaustion-of-cd4-and-cd8-t-cells-during-bovine-leukemia-virus-infection
#9
Tomohiro Okagawa, Satoru Konnai, Asami Nishimori, Naoya Maekawa, Shinya Goto, Ryoyo Ikebuchi, Junko Kohara, Yasuhiko Suzuki, Shinji Yamada, Yukinari Kato, Shiro Murata, Kazuhiko Ohashi
Bovine leukemia virus (BLV) is a retrovirus that infects B cells in cattle and causes bovine leukosis after a long latent period. Progressive exhaustion of T cell functions is considered to facilitate disease progression of BLV infection. Programmed death-1 (PD-1) and lymphocyte activation gene-3 (LAG-3) are immunoinhibitory receptors that contribute to T-cell exhaustion caused by BLV infection in cattle. However, it is unclear whether the cooperation of PD-1 and LAG-3 accelerates disease progression of BLV infection...
June 19, 2018: Veterinary Research
https://www.readbyqxmd.com/read/29913444/stimulation-of-eryptosis-by-afatinib
#10
Abdulla Al Mamun Bhuyan, Florian Lang
BACKGROUND/AIMS: The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor afatinib is primarily utilized for the treatment of non-small cell lung carcinoma. The drug is at least partially effective by triggering suicidal tumor cell death. Side effects of afatinib treatment include anemia. At least in theory, afatinib induced anemia could be secondary to stimulation of suicidal erythrocyte death or eryptosis, characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface...
June 15, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29912176/mk-0677-a-ghrelin-agonist-alleviates-amyloid-beta-related-pathology-in-5xfad-mice-an-animal-model-of-alzheimer-s-disease
#11
Yu-On Jeong, Soo Jung Shin, Jun Yong Park, Bo Kyeong Ku, Ji Soo Song, Jwa-Jin Kim, Seong Gak Jeon, Sang Min Lee, Minho Moon
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by cognitive deficits, neuroinflammation, and neuronal death. The primary pathogenic cause is believed to be the accumulation of pathogenic amyloid beta (Aβ) assemblies in the brain. Ghrelin, which is a peptide hormone predominantly secreted from the stomach, is an endogenous ligand for the growth hormone secretagogue-receptor type 1a (GHS-R1a). MK-0677 is a ghrelin agonist that potently stimulates the GHS-R1a ghrelin receptor...
June 18, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29911936/inhibition-of-the-raf-1-kinase-inhibitory-protein-rkip-by-locostatin-induces-cell-death-and-reduces-the-cxcr4-mediated-migration-of-chronic-lymphocytic-leukemia-cells
#12
Kyle Crassini, Tahni Pyke, Yandong Shen, William S Stevenson, Richard I Christopherson, Stephen P Mulligan, Oliver Giles Best
The Raf-1 kinase inhibitory protein (RKIP) is an important regulatory element in multiple signaling pathways, including MAPK-ERK1/2. We investigated whether targeted disruption of RKIP is a therapeutic option for chronic lymphocytic leukemia (CLL). The RKIP inhibitor locostatin-induced apoptosis of CLL cells, irrespective of poor prognostic indications or treatment history. Locostatin down-regulated MAPK-ERK1/2 and AKT phosphorylation, decreased expression of the chemokine receptor CXCR4 (p = .04) and reduced the migratory capacity of CLL cells toward stroma-derived factor 1α (SDF-1α, p = ...
June 18, 2018: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29911259/intercellular-communications-redox-interactions-in-radiation-toxicity-potential-targets-for-radiation-mitigation
#13
Bagher Farhood, Nasser Hashemi Goradel, Keywan Mortezaee, Neda Khanlarkhani, Ensieh Salehi, Maryam Shabani Nashtaei, Dheyauldeen Shabeeb, Ahmed Eleojo Musa, Hengameh Fallah, Masoud Najafi
Nowadays, using ionizing radiation (IR) is necessary for clinical, agricultural, nuclear energy or industrial applications. Accidental exposure to IR after a radiation terror or disaster poses a threat to human. In contrast to the old dogma of radiation toxicity, several experiments during the last two recent decades have revealed that intercellular signaling and communications play a key role in this procedure. Elevated level of cytokines and other intercellular signals increase oxidative damage and inflammatory responses via reduction/oxidation interactions (redox system)...
June 17, 2018: Journal of Cell Communication and Signaling
https://www.readbyqxmd.com/read/29910819/decitabine-enhances-v%C3%AE-9v%C3%AE-2-t-cell-mediated-cytotoxic-effects-on-osteosarcoma-cells-via-the-nkg2dl-nkg2d-axis
#14
Zhan Wang, Zenan Wang, Shu Li, Binghao Li, Lingling Sun, Hengyuan Li, Peng Lin, Shengdong Wang, Wangsiyuan Teng, Xingzhi Zhou, Zhaoming Ye
γδ T cell-based immunotherapy for osteosarcoma (OS) has shown limited success thus far. DNA-demethylating agents not only induce tumor cell death but also have an immunomodulatory function. In this study, we have assessed the potential benefit of combining decitabine (DAC, a DNA demethylation drug) and γδ T cells for OS immunotherapy. DAC increased the expression of natural killer group 2D (NKG2D) ligands (NKG2DLs), including major histocompatibility complex class I-related chains B (MICB) and UL16-binding protein 1 (ULBP1), on the OS cell surface, making the cells more sensitive to recognition and destruction by cytotoxic γδ T cells...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29910814/the-role-of-natural-killer-group-2-member-d-in-chronic-inflammation-and-autoimmunity
#15
REVIEW
Marina Babic, Chiara Romagnani
Current medicine and medical science puts great effort into elucidating the basis of chronicity and finding appropriate treatments for inflammatory diseases; however, the mechanisms driving aberrant immune responses are mostly unknown and deserve further study. Of particular interest is the identification of checkpoints that regulate the function and differentiation of pro-inflammatory cells during pathogenesis, along with means of their modulation for therapeutic purposes. Natural killer group 2, member D (NKG2D) is a potent activator of the immune system, known as a sensor for "induced-self" ligands, i...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29910711/functional-consequences-of-the-postnatal-switch-from-neonatal-to-mutant-adult-glycine-receptor-%C3%AE-1-subunits-in-the-shaky-mouse-model-of-startle-disease
#16
Natascha Schaefer, Fang Zheng, Johannes van Brederode, Alexandra Berger, Sophie Leacock, Hiromi Hirata, Christopher J Paige, Robert J Harvey, Christian Alzheimer, Carmen Villmann
Mutations in GlyR α1 or β subunit genes in humans and rodents lead to severe startle disease characterized by rigidity, massive stiffness and excessive startle responses upon unexpected tactile or acoustic stimuli. The recently characterized startle disease mouse mutant shaky carries a missense mutation (Q177K) in the β8-β9 loop within the large extracellular N-terminal domain of the GlyR α1 subunit. This results in a disrupted hydrogen bond network around K177 and faster GlyR decay times. Symptoms in mice start at postnatal day 14 and increase until premature death of homozygous shaky mice around 4-6 weeks after birth...
2018: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29910635/impact-of-semaphorin-expression-on-prognostic-characteristics-in-breast-cancer
#17
REVIEW
Ramesh Butti, Totakura Vs Kumar, Ramakrishna Nimma, Gopal C Kundu
Breast cancer is one of the major causes of cancer-related deaths among women worldwide. Aberrant regulation of various growth factors, cytokines, and other proteins and their receptors in cancer cells drives the activation of various oncogenic signaling pathways that lead to cancer progression. Semaphorins are a class of proteins which are differentially expressed in various types of cancer including breast cancer. Earlier, these proteins were known to have a major function in the nerve cell adhesion, migration, and development of the central nervous system...
2018: Breast Cancer: Targets and Therapy
https://www.readbyqxmd.com/read/29909454/inhibition-of-toll-like-receptor-4-tlr-4-improves-neurobehavioral-outcomes-after-acute-ischemic-stroke-in-diabetic-rats-possible-role-of-vascular-endothelial-tlr-4
#18
Yasir Abdul, Mohammed Abdelsaid, Weiguo Li, R Clinton Webb, Jennifer C Sullivan, Guangkuo Dong, Adviye Ergul
Diabetes increases the risk of occurrence and poor functional recovery after ischemic stroke injury. Previously, we have demonstrated greater hemorrhagic transformation (HT), edema, and more severe functional deficits after stroke in diabetic animals that also presented with cerebral vasoregression and endothelial cell death in the recovery period. Given that Toll-like receptor 4 (TLR-4) activation in microvascular endothelial cells triggers a robust inflammatory response, we hypothesized that inhibition of TLR-4 signaling prevents endothelial cell death and improves outcomes after stroke...
June 16, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29909423/prucalopride-inhibits-proliferation-of-ovarian-cancer-cells-via-phosphatidylinositol-3-kinase-pi3k-signaling-pathway
#19
Xiaolin Liu, Yintao Xu, Lu Zhang, Ting Liu, Hui Zhang
BACKGROUND Ovarian cancer is the second most common malignant tumor of the female reproductive system and is the leading cause of death of gynecological malignancies, but at present there is no effective and safe therapy. There is no previously published report on the anti-cancer effect of prucalopride, which is a high-affinity 5-HT4 receptor. The aim of the present study was to determine whether prucalopride can inhibit proliferation of ovarian cancer cells. MATERIAL AND METHODS The cell viability was detected by use of the Cell Counting Kit-8 (CCK-8) assay...
June 17, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29908886/the-potential-role-of-substance-p-in-brainstem-homeostatic-control-in-the-pathogenesis-of-sudden-infant-death-syndrome-sids
#20
REVIEW
Fiona M Bright, Robert Vink, Roger W Byard
Victims of sudden infant death syndrome (SIDS) are believed to have an underlying dysfunction in medullary homeostatic control that impairs critical responses to life threatening challenges such as hypoxia, hypercarbia and asphyxia, often during a sleep period. This failure is thought to result from abnormalities in a network of neural pathways in the medulla oblongata that control respiration, chemosensitivity, autonomic function and arousal. Studies have mainly focused on the role of serotonin, 5-hydroxytyptamine (5HT), although the neuropeptide substance P (SP) has also been shown to play an integral role in the modulation of medullary homeostatic function, often in conjunction with 5-HT...
May 5, 2018: Neuropeptides
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