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Molecular pathology

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https://www.readbyqxmd.com/read/29775457/potassium-and-sodium-microdomains-in-thin-astroglial-processes-a-computational-model-study
#1
Kevin Breslin, John Joseph Wade, KongFatt Wong-Lin, Jim Harkin, Bronac Flanagan, Harm Van Zalinge, Steve Hall, Matthew Walker, Alexei Verkhratsky, Liam McDaid
A biophysical model that captures molecular homeostatic control of ions at the perisynaptic cradle (PsC) is of fundamental importance for understanding the interplay between astroglial and neuronal compartments. In this paper, we develop a multi-compartmental mathematical model which proposes a novel mechanism whereby the flow of cations in thin processes is restricted due to negatively charged membrane lipids which result in the formation of deep potential wells near the dipole heads. These wells restrict the flow of cations to "hopping" between adjacent wells as they transverse the process, and this surface retention of cations will be shown to give rise to the formation of potassium (K+) and sodium (Na+) microdomains at the PsC...
May 18, 2018: PLoS Computational Biology
https://www.readbyqxmd.com/read/29775224/circular-rnas-are-differentially-expressed-in-liver-ischemia-reperfusion-injury-model
#2
Zhiqiang Ye, Qinglei Kong, Jianhua Han, Jingyi Deng, Miaolue Wu, Hong Deng
Liver ischemia/reperfusion (I/R) injury has high mortality due to the intense inflammatory process occurs in the liver. However, the pathological mechanism underlying I/R injury is still not clear. Recent works showed that circular RNAs play critical roles in many human diseases. In this study, the occurrence of liver I/R injury was validated by an analysis of the blood samples and hematoxylin-eosin (HE) staining of liver tissues. Total RNA was purified and followed by RNA-seq in the purpose of screening the circRNAs in significant differentially expression, which were validated by quantitative PCR...
May 18, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29774877/-analysis-of-prognostic-factors-for-survival-in-elderly-patients-with-glioma
#3
Jinghui Liu, Miao Lou, Peigang Ji, Chen Li, Fuqiang Feng, Baofu Li, Meng Xu, Guodong Gao, Yan Qu, Liang Wang
To analyze the prognostic factors for survival in elderly patients with glioma.
 Methods: We performed a retrospective analysis of prognostic factors for elderly patients with glioma, who were treated by the same attending doctor during June 2014 and June 2016, to investigate the correlations of the age, dimension of pathology, histological grade, extent of resection, adjuvant therapy, preoperative Karnofsky Performance Scale (KPS) score, postoperative KPS score, molecular markers [isocitrate dehydrogenase-1 (IDH-1), O6-methylguanine DNA-transferase (MGMT), epidermal growth factor receptor (EGFR), Ki-67] with the prognosis...
April 28, 2018: Zhong Nan da Xue Xue Bao. Yi Xue Ban, Journal of Central South University. Medical Sciences
https://www.readbyqxmd.com/read/29774544/functional-molecules-in-mesothelial-to-mesenchymal-transition-revealed-by-transcriptome-analyses
#4
Sara Namvar, Adrian S Woolf, Leo A H Zeef, Thomas Wilm, Bettina Wilm, Sarah E Herrick
Peritoneal fibrosis is a common complication of abdominal and pelvic surgery, and can also be triggered by peritoneal dialysis, resulting in treatment failure. In these settings, fibrosis is driven by activated myofibroblasts that are considered to be partly derived by mesothelial-to-mesenchymal transition (MMT). We hypothesised that if the molecular signature of MMT could be better defined, these insights could be exploited to block this pathological cellular transition. Rat peritoneal mesothelial cells were purified, using an antibody to HBME1, a protein present on mesothelial cell microvilli, and streptavidin nanobead technology...
May 17, 2018: Journal of Pathology
https://www.readbyqxmd.com/read/29774336/raman-fingerprints-of-amyloid-structures
#5
Jessica D Flynn, Jennifer C Lee
Structural differences in pathological and functional amyloid fibrils have been investigated by Raman microspectroscopy. Second-derivative analyses of amide-I and amide-III bands distinguish parallel in-register β-sheets from a β-solenoid. Further, spatially resolved Raman spectra reveal molecular heterogeneity in amyloid structures.
May 18, 2018: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/29774141/exosome-mediated-peritoneal-dissemination-in-gastric-cancer-and-its-clinical-applications
#6
REVIEW
Kai-Bo Chen, Jian Chen, Xiao-Li Jin, Yi Huang, Qiu-Ming Su, Li Chen
The prognosis of patients with peritoneal dissemination from gastric cancer is poor, and the underlying molecular mechanism remains unclear. Exosomes, as macromolecular phospholipid bilayer vesicles comprising of proteins, nucleic acids and lipids, serve as mediators of cell-cell communication. Gastric cancer tumor-derived exosomes may be involved in the pathological process of peritoneal dissemination by mediating crosstalk between cancer cells and mesothelial cells, to result in the induction of enhanced tumor growth, migratory, adhesive and invasive abilities, peritoneal fibrosis and apoptosis, mesothelial-to-mesenchymal transition, angiogenesis and chemoresistance...
June 2018: Biomedical Reports
https://www.readbyqxmd.com/read/29774009/signaling-pathways-and-cellular-mechanisms-regulating-mossy-fiber-sprouting-in-the-development-of-epilepsy
#7
REVIEW
Christin M Godale, Steve C Danzer
The sprouting of hippocampal dentate granule cell axons, termed mossy fibers, into the dentate inner molecular layer is one of the most consistent findings in tissue from patients with mesial temporal lobe epilepsy. Decades of research in animal models have revealed that mossy fiber sprouting creates de novo recurrent excitatory connections in the hippocampus, fueling speculation that the pathology may drive temporal lobe epileptogenesis. Conducting definitive experiments to test this hypothesis, however, has been challenging due to the difficulty of dissociating this sprouting from the many other changes occurring during epileptogenesis...
2018: Frontiers in Neurology
https://www.readbyqxmd.com/read/29773993/diabetic-cardiomyopathy-impact-of-biological-sex-on-disease-development-and-molecular-signatures
#8
REVIEW
Ryan Toedebusch, Anthony Belenchia, Lakshmi Pulakat
Diabetic cardiomyopathy refers to a unique set of heart-specific pathological variables induced by hyperglycemia and insulin resistance. Given that cardiovascular disease (CVD) is the leading cause of death in the world, and type 2 diabetes incidence continues to rise, understanding the complex interplay between these two morbidities and developing novel therapeutic strategies is vital. Two hallmark characteristics specific to diabetic cardiomyopathy are diastolic dysfunction and cardiac structural mal-adaptations, arising from cardiac cellular responses to the complex toxicity induced by hyperglycemia with or without hyperinsulinemia...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29773599/tgf%C3%AE-1-mediated-functional-inhibition-of-mesenchymal-stromal-cells-in-myelodysplastic-syndromes-and-acute-myeloid-leukemia
#9
Stefanie Geyh, Manuel Rodríguez-Paredes, Paul Jäger, Annemarie Koch, Felix Bormann, Julian Gutekunst, Christoph Zilkens, Ulrich Germing, Guido Kobbe, Frank Lyko, Rainer Haas, Thomas Schroeder
Mesenchymal stromal cells are involved in the pathogenesis of myelodysplastic syndromes and acute myeloid leukemia, but the underlying mechanisms are incompletely understood. To further characterize the pathological phenotype we performed RNA sequencing of mesenchymal stromal cells from patients with myelodysplastic syndromes and acute myeloid leukemia revealing a specific molecular signature of genes commonly deregulated in myelodysplastic syndromes and acute myeloid leukemia. Pathway analysis showed a strong enrichment of genes related to osteogenesis, senescence, inflammation and inhibitory cytokines thereby reflecting the structural and functional deficits of mesenchymal stromal cells in myelodysplastic syndromes and acute myeloid leukemia on a molecular level...
May 17, 2018: Haematologica
https://www.readbyqxmd.com/read/29773426/stem-cell-transcription-factor-sox2-in-synovial-sarcoma-and-other-soft-tissue-tumors
#10
Heba Zayed, Iver Petersen
BACKGROUND: SOX2 has gained considerable interest as a pluripotency inducing gene. Co-transfection of SOX2 together with NANOG, KLF4 and c-MYC into adult fibroblasts was able to generate pluripotent stem cells. SOX2 has been reported to be expressed in synovial sarcoma, a tumor being characterized by the SS18-SSX gene fusion forming part of the SWI/SNF chromatin remodeling complex that affects histone methylation. The role of SOX2 in this tumor type as well as other soft tissue tumor entities however is still poorly characterized...
May 4, 2018: Pathology, Research and Practice
https://www.readbyqxmd.com/read/29773145/pathological-and-molecular-characterization-of-systemic-isosporosis-atoxoplasmosis-in-captive-green-winged-saltator-saltator-similis
#11
Ayisa Rodrigues de Oliveira, Tayse Domingues de Souza, Juliana P S Mol, Mayra Cunha Flecher, Emy Hiura, Renato Lima Santos
Systemic isosporosis, also called atoxoplasmosis or visceral coccidiosis, is a disease that affects birds in general. Pathogenesis of systemic isosporosis and its etiologic agent have not been well characterized, but taxonomically Atoxoplasma is currently considered a junior objective synonym of Isospora. The present report aimed to describe pathological and molecular findings of systemic isosporosis in captive green-winged saltators (Saltator similis) from the State of Espírito Santo, Brazil. In a commercial breeding facility eleven birds with two to nine months of age died from 2015 to 2016...
May 15, 2018: Veterinary Parasitology
https://www.readbyqxmd.com/read/29772837/conventional-pathology-versus-gene-signatures-for-assessing-luminal-a-and-b-type-breast-cancers-results-of-a-prospective-cohort-study
#12
Julia E C van Steenhoven, Anne Kuijer, Paul J van Diest, Joost M van Gorp, Marieke Straver, Sjoerd G Elias, Jelle Wesseling, Emiel Rutgers, Johanna N H Timmer-Bonte, Peter Nieboer, Tineke J Smilde, Alex Imholz, Charlotte F J M Blanken, Sabine Siesling, Thijs van Dalen
In this study, in estrogen receptor positive (ER+) early stage breast cancer patients who were considered candidates for 70-gene signature (70-GS, "MammaPrint") use, we compared molecular subtyping (MS) based on the previously validated 80-gene signature (80-GS, "BluePrint") versus surrogate pathological subtyping (PS). Between 1 January 2013 and 31 December 2015, 595 clinical intermediate risk ER+ early stage breast cancer patients were enrolled. Hormone receptor (HR) and HER2 receptor status were determined by conventional pathology using immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH)...
May 17, 2018: Genes
https://www.readbyqxmd.com/read/29772777/oxidative-stress-in-preeclampsia-and-placental-diseases
#13
REVIEW
Rajaa Aouache, Louise Biquard, Daniel Vaiman, Francisco Miralles
Preeclampsia is a persistent hypertensive gestational disease characterized by high blood pressure and proteinuria, which presents from the second trimester of pregnancy. At the cellular level, preeclampsia has largely been associated with the release of free radicals by the placenta. Placenta-borne oxidative and nitrosative stresses are even sometimes considered as the major molecular determinants of the maternal disease. In this review, we present the recent literature evaluating free radical production in both normal and pathological placentas (including preeclampsia and other major pregnancy diseases), in humans and animal models...
May 17, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29772697/structure-activity-relationships-based-on-3d-qsar-comfa-comsia-and-design-of-aryloxypropanol-amine-agonists-with-selectivity-for-the-human-%C3%AE-3-adrenergic-receptor-and-anti-obesity-and-anti-diabetic-profiles
#14
Marcos Lorca, Cesar Morales-Verdejo, David Vásquez-Velásquez, Juan Andrades-Lagos, Javier Campanini-Salinas, Jorge Soto-Delgado, Gonzalo Recabarren-Gajardo, Jaime Mella
The wide tissue distribution of the adrenergic β3 receptor makes it a potential target for the treatment of multiple pathologies such as diabetes, obesity, depression, overactive bladder (OAB), and cancer. Currently, there is only one drug on the market, mirabegron, approved for the treatment of OAB. In the present study, we have carried out an extensive structure-activity relationship analysis of a series of 41 aryloxypropanolamine compounds based on three-dimensional quantitative structure-activity relationship (3D-QSAR) techniques...
May 16, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29772538/targeting-fibroblast-activation-protein-in-cancer-prospects-and-caveats
#15
Petr Busek, Rosana Mateu, Michal Zubal, Lenka Kotackova, Aleksi Sedo
Fibroblast activation protein (FAP, seprase) is a serine protease with post-proline dipeptidyl peptidase and endopeptidase enzymatic activity. FAP is upregulated in several tumor types, while its expression in healthy adult tissues is scarce. FAP molecule itself and FAP+ stromal cells play an important although probably context-dependent and tumor type-specific pathogenetic role in tumor progression. We provide an overview of FAP expression under both physiological and pathological conditions with focus on human malignancies...
June 1, 2018: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/29772420/the-search-for-biomarkers-of-hepatocellular-carcinoma-and-the-impact-on-patient-outcome
#16
REVIEW
Alyson P Black, Anand S Mehta
Hepatocellular carcinoma (HCC) is the 5th most common cancer, but the 3rd leading cause of cancer death globally with approximately 700,000 fatalities annually. The severity of this cancer arises from its difficulty to detect and treat. The major etiologies of HCC are liver fibrosis or cirrhosis from chronic viral infections, as well as metabolic conditions. Since most cases arise from prior pathologies, biomarker surveillance in high-risk individuals is an essential approach for early detection and improved patient outcome...
May 14, 2018: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/29771769/systemic-chemotherapy-for-advanced-rare-pancreatic-histotype-tumors-a-retrospective-multicenter-analysis
#17
Oronzo Brunetti, Giuseppe Aprile, Paolo Marchetti, Enrico Vasile, Andrea Casadei Gardini, Mario Scartozzi, Sandro Barni, Sara Delfanti, Fernando De Vita, Francesco Di Costanzo, Michele Milella, Chiara Alessandra Cella, Rossana Berardi, Ivana Cataldo, Aldo Scarpa, Debora Basile, Federica Mazzuca, Giusi Graziano, Antonella Argentiero, Daniele Santini, Michele Reni, Stefano Cascinu, Nicola Silvestris
OBJECTIVES: Two issues were put forth by clinicians in the management of the advanced stages of rare variants of pancreatic ductal adenocarcinoma and other exocrine histotypes with peculiar clinical and pathological features: Do chemotherapy regimens recommended in pancreatic ductal adenocarcinoma patients have a clinical activity in rare pancreatic tumors? Or should other chemotherapy combinations be considered in this subset of patients? METHODS: We conducted a multicenter retrospective study that collected data from 2005 to 2016 at 14 Italian cancer centers with the aim to evaluate tumor response and time to progression for first- and second-line and overall survival...
May 15, 2018: Pancreas
https://www.readbyqxmd.com/read/29770992/holoprosencephaly-in-the-genomics-era
#18
Erich Roessler, Ping Hu, Maximilian Muenke
Holoprosencephaly (HPE) is the direct consequence of specific genetic and/or environmental insults interrupting the midline specification of the nascent forebrain. Such disturbances can lead to a broad range of phenotypic consequences for the brain and face in humans. This malformation sequence is remarkably common in utero (1 in 250 human fetuses), but 97% typically do not survive to birth. The precise molecular pathogenesis of HPE in these early human embryos remains largely unknown. Here, we outline our current understanding of the principal driving factors leading to HPE pathologies and elaborate our multifactorial integrated genomics approach...
May 17, 2018: American Journal of Medical Genetics. Part C, Seminars in Medical Genetics
https://www.readbyqxmd.com/read/29770354/3d-co-culture-system-of-tumor-associated-macrophages-and-ovarian-cancer-cells
#19
Lingli Long, Mingzhu Yin, Wang Min
Ovarian cancer is fairly unique in that ovarian carcinoma cells can detach and spread directly through peritoneal cavity. It has been unclear, however, how detached cancer cells survive in the peritoneum and form spheroid structure. We have recently reported that there is a strong correlation between Tumor-associated macrophages (TAMs)-associated spheroid and clinical pathology of ovarian cancer, and that TAMs promote spheroid formation and tumor growth at early stages of transcoelomic metastasis in orthotopic mouse models...
April 20, 2018: Bio-protocol
https://www.readbyqxmd.com/read/29769405/%C3%AE-synuclein-stimulation-of-monoamine-oxidase-b-and-legumain-protease-mediates-the-pathology-of-parkinson-s-disease
#20
Seong Su Kang, Eun Hee Ahn, Zhentao Zhang, Xia Liu, Fredric P Manfredsson, Ivette M Sandoval, Susov Dhakal, P Michael Iuvone, Xuebing Cao, Keqiang Ye
Dopaminergic neurodegeneration in Parkinson's disease (PD) is associated with abnormal dopamine metabolism by MAO-B (monoamine oxidase-B) and intracellular α-Synuclein (α-Syn) aggregates, called the Lewy body. However, the molecular relationship between α-Syn and MAO-B remains unclear. Here, we show that α-Syn directly binds to MAO-B and stimulates its enzymatic activity, which triggers AEP (asparagine endopeptidase; legumain) activation and subsequent α-Syn cleavage at N103, leading to dopaminergic neurodegeneration...
May 16, 2018: EMBO Journal
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