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https://www.readbyqxmd.com/read/28645087/ep2-receptor-agonist-ono-ae1-259-01-attenuates-pentylenetetrazole-and-pilocarpine-induced-seizures-but-causes-hippocampal-neurotoxicity
#1
Aline Carré Santos, Fernanda Rossatto Temp, Joseane Righes Marafiga, Micheli Mainardi Pillat, Amanda Titzel Hessel, Leandro Rodrigo Ribeiro, Lígia Gomes Miyazato, Mauro Schneider Oliveira, Carlos Fernando Mello
Epilepsy is a common and devastating neurological disease affecting more than 50 million people worldwide. Accumulating experimental and clinical evidence suggests that inflammatory pathways contribute to the development of seizures in various forms of epilepsy. In this context, while the activation of the PGE2 EP2 receptor causes early neuroprotective and late neurotoxic effects, the role of EP2 receptor in seizures remains unclear. We investigated whether the systemic administration of the highly selective EP2 agonist ONO-AE1-259-01 prevented acute pentylenetetrazole (PTZ)- and pilocarpine-induced seizures...
June 20, 2017: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/28645055/c-reactive-protein-and-white-blood-cell-levels-in-schizophrenia-bipolar-disorders-and-depression-associations-with-mortality-and-psychiatric-outcomes-a-population-based-study
#2
H T Horsdal, O Köhler-Forsberg, M E Benros, C Gasse
BACKGROUND: Mental disorders have been associated with increased levels of inflammatory markers, which can affect disease trajectories. We aimed to assess levels of C-reactive protein (CRP) and white blood cells (WBC) across individuals with schizophrenia, bipolar disorder, and depression, and to investigate associations with subsequent psychiatric admission and mortality. METHODS: We identified all adults in the Central Denmark Region during 2000-2012 with a first diagnosis of schizophrenia, bipolar disorder, or depression and a baseline measurement of CRP and/or WBC count...
May 17, 2017: European Psychiatry: the Journal of the Association of European Psychiatrists
https://www.readbyqxmd.com/read/28645028/lipid-homeostasis-and-regulated-cell-death
#3
REVIEW
Eran Agmon, Brent R Stockwell
Modern lipidomics analysis paints a dynamic picture of membrane organizations, as changing and adapting lipid assemblies that play an active role in cellular function. This article highlights how the lipid composition of membranes determines specific organelle functions, how homeostatic mechanisms maintain these functions by regulating physical properties of membranes, and how cells disrupt lipid homeostasis to bring about regulated cell death (RCD). These are broad phenomena, and representative examples are reviewed here...
June 20, 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/28644953/helping-induced-hpscs-clean-up-their-act
#4
Ho-Chang Jeong, Hyuk-Jin Cha
Inhibition of the tumorigenic potential of human pluripotent stem cells (hPSCs) remains critically important for safe hPSC-based therapy. In this issue of Cell Chemical Biology, Kuang et al. (2017) reveal that the phospho-D-peptide D-3 efficiently induces death of residual hPSCs, but not of differentiated progenies, through high alkaline phosphatase activity in hPSCs.
June 22, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28644949/hematopoietic-cell-transplantation-for-acute-lymphoblastic-leukemia-in-adult-patients
#5
REVIEW
Riad El Fakih, Syed Ahmed, Feras Alfraih, Amr Hanbali
Acute lymphoblastic leukemia (ALL) consists of precursor B ALL or T ALL phenotypes. In the pediatric population, ALL patients enjoy an 80% long-term survival with the current pediatric chemotherapy protocols as compared with 50% long-term survival in the adult population. In adults, complete remission rates are similar to those of pediatric patients; however, long-term survival is much lower with the majority of deaths attributable to relapsed disease. Postremission consolidation strategies in adults include chemotherapy, autologous, or allogeneic transplant...
June 15, 2017: Hematology/oncology and Stem Cell Therapy
https://www.readbyqxmd.com/read/28644706/advance-care-planning-and-palliative-care-integration-for-patients-undergoing-hematopoietic-stem-cell-transplantation
#6
Winnie S Wang, Joseph D Ma, Sandahl H Nelson, Carolyn Revta, Gary T Buckholz, Carolyn M Mulroney, Eric J Roeland
PURPOSE: Advance care planning (ACP) in hematopoietic stem-cell transplantation (HSCT) is challenging, given the potential for cure despite increased morbidity and mortality risk.The aim of this study was to evaluate ACP and palliative care (PC) integration for patients who underwent HSCT. METHODS: A retrospective analysis was conducted and data were extracted from electronic medical records of patients who underwent HSCT between January 2011 and December 2015. Patients who received more than one transplant and who were younger than 18 years of age were excluded...
June 23, 2017: Journal of Oncology Practice
https://www.readbyqxmd.com/read/28644496/the-role-of-soybean-extracts-and-isoflavones-in-hormone-dependent-breast-cancer-aromatase-activity-and-biological-effects
#7
Cristina Amaral, Maria Regina T Toloi, Luis Daniel Vasconcelos, Maria José V Fonseca, Georgina Correia-da-Silva, Natércia Teixeira
Estrogen receptor-positive (ER(+)) breast cancer is the most common cause of cancer death in women worldwide. Nowadays, the relationship between soya diet and breast cancer is controversial due to the unknown role of its isoflavones, genistein (G) and daidzein (D). In this work, we investigated not only the anti-tumor properties of a soybean extract (NBSE) but also whether the biotransformation of extract (BSE) by the fungus Aspergillus awamori increased its effectiveness. The BSE showed a stronger anti-aromatase activity and anti-proliferative efficacy in ER(+) aromatase-overexpressing breast cancer cells...
June 23, 2017: Food & Function
https://www.readbyqxmd.com/read/28644464/a-synthetic-ion-transporter-that-disrupts-autophagy-and-induces-apoptosis-by-perturbing-cellular-chloride-concentrations
#8
Nathalie Busschaert, Seong-Hyun Park, Kyung-Hwa Baek, Yoon Pyo Choi, Jinhong Park, Ethan N W Howe, Jennifer R Hiscock, Louise E Karagiannidis, Igor Marques, Vítor Félix, Wan Namkung, Jonathan L Sessler, Philip A Gale, Injae Shin
Perturbations in cellular chloride concentrations can affect cellular pH and autophagy and lead to the onset of apoptosis. With this in mind, synthetic ion transporters have been used to disturb cellular ion homeostasis and thereby induce cell death; however, it is not clear whether synthetic ion transporters can also be used to disrupt autophagy. Here, we show that squaramide-based ion transporters enhance the transport of chloride anions in liposomal models and promote sodium chloride influx into the cytosol...
July 2017: Nature Chemistry
https://www.readbyqxmd.com/read/28644441/micrornas-143-and-145-induce-epithelial-to-mesenchymal-transition-and-modulate-the-expression-of-junction-proteins
#9
Lidia Avalle, Danny Incarnato, Aurora Savino, Marta Gai, Francesca Marino, Sara Pensa, Isaia Barbieri, Michael B Stadler, Paolo Provero, Salvatore Oliviero, Valeria Poli
Transforming growth factor (TGF)-β is one of the major inducers of epithelial to mesenchymal transition (EMT), a crucial program that has a critical role in promoting carcinoma's metastasis formation. MicroRNAs-143 and -145, which are both TGF-β direct transcriptional targets, are essential for the differentiation of vascular smooth muscle cells (VSMC) during embryogenesis, a TGF-β-dependent process reminiscent of EMT. Their role in adult tissues is however less well defined and even ambiguous, as their expression was correlated both positively and negatively with tumor progression...
June 23, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28644440/lncrna-sarcc-suppresses-renal-cell-carcinoma-rcc-progression-via-altering-the-androgen-receptor-ar-mirna-143-3p-signals
#10
Wei Zhai, Yin Sun, Changcheng Guo, Guanghui Hu, Mingchao Wang, Jiayi Zheng, WanYing Lin, Qingbo Huang, Gonghui Li, Junhua Zheng, Chawnshang Chang
While the androgen receptor (AR) might promote renal cell carcinoma (RCC) initiation and progression, the molecular mechanisms involved remain largely unclear. Here, we discovered the novel LncRNA-SARCC, which was suppressed and associated with better prognosis in RCC. Preclinical studies using multiple RCC cells and in vivo mouse model indicated that LncRNA-SARCC could attenuate RCC cell invasion, migration and proliferation in vitro and in vivo. Mechanistically, LncRNA-SARCC bound and destabilized AR protein with an inhibition of AR function, which led to transcriptionally de-repress miR-143-3p expression, thus inhibition of its downstream signals including AKT, MMP-13, K-RAS and P-ERK...
June 23, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28644439/activation-of-cell-surface-grp78-decreases-endoplasmic-reticulum-stress-and-neuronal-death
#11
Morgane Louessard, Isabelle Bardou, Eloïse Lemarchand, Audrey M Thiebaut, Jérôme Parcq, Jérôme Leprince, Anne Terrisse, Valérie Carraro, Pierre Fafournoux, Alain Bruhat, Cyrille Orset, Denis Vivien, Carine Ali, Benoit D Roussel
The unfolded protein response (UPR) is an endoplasmic reticulum (ER) -related stress conserved pathway that aims to protect cells from being overwhelmed. However, when prolonged, UPR activation converts to a death signal, which relies on its PERK-eIF2α branch. Overactivation of the UPR has been implicated in many neurological diseases, including cerebral ischaemia. Here, by using an in vivo thromboembolic model of stroke on transgenic ER stress-reporter mice and neuronal in vitro models of ischaemia, we demonstrate that ischaemic stress leads to the deleterious activation of the PERK branch of the UPR...
June 23, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28644437/more-alive-than-dead-non-apoptotic-roles-for-caspases-in-neuronal-development-plasticity-and-disease
#12
REVIEW
Amrita Mukherjee, Darren W Williams
Nervous systems are arguably the most fascinating and complex structures in the known universe. How they are built, changed by experience and then degenerate are some of the biggest questions in biology. Regressive phenomena, such as neuron pruning and programmed cell death, have a key role in the building and maintenance of the nervous systems. Both of these cellular mechanisms deploy the caspase family of protease enzymes. In this review, we highlight the non-apoptotic function of caspases during nervous system development, plasticity and disease, particularly focussing on their role in structural remodelling...
June 23, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28644436/the-lats1-and-lats2-tumor-suppressors-beyond-the-hippo-pathway
#13
REVIEW
Noa Furth, Yael Aylon
Proper cellular functionality and homeostasis are maintained by the convergent integration of various signaling cascades, which enable cells to respond to internal and external changes. The Dbf2-related kinases LATS1 and LATS2 (LATS) have emerged as central regulators of cell fate, by modulating the functions of numerous oncogenic or tumor suppressive effectors, including the canonical Hippo effectors YAP/TAZ, the Aurora mitotic kinase family, estrogen signaling and the tumor suppressive transcription factor p53...
June 23, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28644435/p53-amyloid-formation-leading-to-its-loss-of-function-implications-in-cancer-pathogenesis
#14
Saikat Ghosh, Shimul Salot, Shinjinee Sengupta, Ambuja Navalkar, Dhiman Ghosh, Reeba Jacob, Subhadeep Das, Rakesh Kumar, Narendra Nath Jha, Shruti Sahay, Surabhi Mehra, Ganesh M Mohite, Santanu K Ghosh, Mamata Kombrabail, Guruswamy Krishnamoorthy, Pradip Chaudhari, Samir K Maji
The transcriptional regulator p53 has an essential role in tumor suppression. Almost 50% of human cancers are associated with the loss of p53 functions, where p53 often accumulates in the nucleus as well as in cytoplasm. Although it has been previously suggested that amyloid formation could be a cause of p53 loss-of-function in subset of tumors, the characterization of these amyloids and its structure-function relationship is not yet established. In the current study, we provide several evidences for the presence of p53 amyloid formation (in human and animal cancer tissues); along with its isolation from human cancer tissues and the biophysical characterization of these tissue-derived fibrils...
June 23, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28644434/ageing-and-hypoxia-cause-protein-aggregation-in-mitochondria
#15
Daniel M Kaufman, Xia Wu, Barbara A Scott, Omar A Itani, Marc R Van Gilst, James E Bruce, C Michael Crowder
Aggregation of cytosolic proteins is a pathological finding in disease states, including ageing and neurodegenerative diseases. We have previously reported that hypoxia induces protein misfolding in Caenorhabditis elegans mitochondria, and electron micrographs suggested protein aggregates. Here, we seek to determine whether mitochondrial proteins actually aggregate after hypoxia and other cellular stresses. To enrich for mitochondrial proteins that might aggregate, we performed a proteomics analysis on purified C...
June 23, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28644433/ctla-4-mediated-posttranslational-modifications-direct-cytotoxic-t-lymphocyte-differentiation
#16
Holger Lingel, Josef Wissing, Aditya Arra, Denny Schanze, Stefan Lienenklaus, Frank Klawonn, Mandy Pierau, Martin Zenker, Lothar Jänsch, Monika C Brunner-Weinzierl
The blockade of inhibitory receptors such as CTLA-4 (CD152) is being used as immune-checkpoint therapy, offering a powerful strategy to restore effective immune responses against tumors. To determine signal components that are induced under the control of CTLA-4 we analyzed activated murine CD8(+) T cells by quantitative proteomics. Accurate mass spectrometry revealed that CTLA-4 engagement led to central changes in the phosphorylation of proteins involved in T-cell differentiation. Beside other targets, we discovered a CTLA-4-mediated induction of the translational inhibitor programmed cell death-4 (PDCD4) as a result of FoxO1 nuclear re-localization...
June 23, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28644395/optical-tracking-and-digital-quantification-of-beating-behavior-in-bioengineered-human-cardiac-organoids
#17
Mahesh Devarasetty, Steven Forsythe, Thomas D Shupe, Shay Soker, Colin E Bishop, Anthony Atala, Aleksander Skardal
Organoid and organ-on-a-chip technologies are rapidly advancing towards deployment for drug and toxicology screening applications. Liver and cardiac toxicities account for the majority of drug candidate failures in human trials. Liver toxicity generally produces liver cell death, while cardiac toxicity causes adverse changes in heart beat kinetics. In traditional 2D cultures, beating kinetics can be measured by electrode arrays, but in some 3D constructs, quantifying beating kinetics can be more challenging...
June 23, 2017: Biosensors
https://www.readbyqxmd.com/read/28644233/tyrosine-kinase-inhibitor-vatalanib-inhibits-proliferation-and-migration-of-human-pterygial-fibroblasts
#18
Hong Kyu Kim, Ji-Young Choi, Sang Min Park, Chang Rae Rho, Kyong Jin Cho, Sangmee Ahn Jo
PURPOSE: Vatalanib is a small-molecule tyrosine kinase inhibitor. We investigated the effects of vatalanib on the proliferation and migration of cultured human pterygial fibroblasts (HPFs). METHODS: Pterygium tissues were obtained after pterygium excision surgery and subjected to primary culture. HPFs were treated with vatalanib at various concentrations. Mitomycin C (MMC) was used as a positive control. Cell proliferation and migration assays were used to investigate the effects of vatalanib...
June 21, 2017: Cornea
https://www.readbyqxmd.com/read/28644129/anti-cd47-antibodies-induce-phagocytosis-of-live-malignant-b-cells-by-macrophages-via-the-fc-domain-resulting-in-cell-death-by-phagoptosis
#19
Lucy E Métayer, Anna Vilalta, G A Amos Burke, Guy C Brown
When expressed on the surface of cells, CD47 inhibits phagocytosis of these cells by phagocytes. Most human cancers overexpress CD47, and antibodies to CD47 have shown a remarkable ability to clear a range of cancers in animal models. However, the mechanism by which these antibodies cause cancer cell death is unclear. We find that CD47 is expressed on the surface of three B-cell lines from human malignancies: 697 (pre-B-ALL lymphoblasts), Ramos and DG-75 (both mature B-cells, Burkitt's lymphoma), and anti-CD47 antibodies greatly increase the phagocytosis of all three cell line by macrophages...
June 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28644106/viability-and-osteogenic-differentiation-of-human-periodontal-ligament-progenitor-cells-are-maintained-after-incubation-with-porphyromonas-gingivalis-protein-extract
#20
Mayra Laino Albiero, Rafael Nóbrega Stipp, Miki Taketomi Saito, Márcio Zaffalon Casati, Enilson Antonio Sallum, Francisco Humberto Nociti, Karina Gonzales Silvério
BACKGROUND: Porphyromonas gingivalis (Pg) is a major periodontal pathogen that contains immunostimulatory components. Periodontal ligament mesenchymal stem cells (PDLSCs) are responsible for regeneration of the periodontium that is lost due to periodontitis. Pathologic factors within the microenvironment that impair resident PDLSCs are not well understood. The present study investigated in vitro the effects of Pg protein extract (PgPE) on the biological properties of CD105-enriched PDL progenitor cell populations (PDL-CD105(+) cells)...
June 23, 2017: Journal of Periodontology
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