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Molecular pathology

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https://www.readbyqxmd.com/read/28239534/transcriptome-and-metabolome-analysis-of-liver-and-kidneys-of-rats-chronically-fed-nk603-roundup-tolerant-genetically-modified-maize
#1
Robin Mesnage, Matthew Arno, Gilles-Eric Séralini, Michael N Antoniou
BACKGROUND: A previous 2-year rat feeding trial assessing potential toxicity of NK603 Roundup-tolerant genetically modified maize revealed blood and urine biochemical changes indicative of liver and kidney pathology. In an effort to obtain deeper insight into these findings, molecular profiling of the liver and kidneys from the same animals was undertaken. RESULTS: Transcriptomics showed no segregation of NK603 maize and control feed groups with false discovery rates ranging from 43 to 83% at a cut-off p value of 1%...
2017: Environmental Sciences Europe
https://www.readbyqxmd.com/read/28239348/genetic-determinants-of-parkinson-s-disease-can-they-help-to-stratify-the-patients-based-on-the-underlying-molecular-defect
#2
REVIEW
Sara Redenšek, Maja Trošt, Vita Dolžan
Parkinson's disease (PD) is a sporadic progressive neurodegenerative brain disorder with a relatively strong genetic background. We have reviewed the current literature about the genetic factors that could be indicative of pathophysiological pathways of PD and their applications in everyday clinical practice. Information on novel risk genes is coming from several genome-wide association studies (GWASs) and their meta-analyses. GWASs that have been performed so far enabled the identification of 24 loci as PD risk factors...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28239331/csp%C3%AE-a-molecular-co-chaperone-essential-for-short-and-long-term-synaptic-maintenance
#3
Elena Lopez-Ortega, Rocío Ruiz, Lucia Tabares
Cysteine string protein α (CSPα) is a vesicle protein located in the presynaptic terminal of most synapses. CSPα is an essential molecular co-chaperone that facilitates the correct folding of proteins and the assembly of the exocytic machinery. The absence of this protein leads to altered neurotransmitter release and neurodegeneration in multiple model systems, from flies to mice. In humans, CSPα mutations are associated with the development of neuronal ceroid lipofuscinosis (NCL), a neurodegenerative disease characterized by intracellular accumulation of lysosomal material...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28238791/selol-an-organic-selenium-donor-prevents-lipopolysaccharide-induced-oxidative-stress-and-inflammatory-reaction-in-the-rat-brain
#4
Agnieszka Dominiak, Anna Wilkaniec, Henryk Jęśko, Grzegorz A Czapski, Anna M Lenkiewicz, Eliza Kurek, Piotr Wroczyński, Agata Adamczyk
Neuroinflammation and oxidative stress are key intertwined pathological factors in many neurological, particularly neurodegenerative diseases, such as Alzheimer's and Parkinson's disorders as well as autism. The present study was conducted to evaluate the protective effects of Selol, an organic selenium donor, against lipopolysaccharide (LPS)-mediated inflammation in rat brain. The results demonstrated that the peripheral administration of LPS in a dose of 100 μg/kg b.w. evoked typical pathological reaction known as systemic inflammatory response...
February 23, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28238593/her2-enriched-subtype-as-a-predictor-of-pathological-complete-response-following-trastuzumab-and-lapatinib-without-chemotherapy-in-early-stage-her2-positive-breast-cancer-pamela-an-open-label-single-group-multicentre-phase-2-trial
#5
Antonio Llombart-Cussac, Javier Cortés, Laia Paré, Patricia Galván, Begoña Bermejo, Noelia Martínez, Maria Vidal, Sònia Pernas, Rafael López, Montserrat Muñoz, Paolo Nuciforo, Serafín Morales, Mafalda Oliveira, Lorena de la Peña, Alexandra Peláez, Aleix Prat
BACKGROUND: HER2-positive breast cancer consists of four intrinsic molecular subtypes-luminal A, luminal B, HER2-enriched, and basal-like-and a normal-like subtype, with the HER2-enriched subtype having the highest activation of the EGFR-HER2 pathway. We aimed to test the hypothesis that patients with the HER2-enriched subtype benefit the most from dual HER2 blockade. METHODS: PAMELA is an open-label, single-group, phase 2 trial done in 19 hospitals in Spain. We recruited female patients aged at least 18 years with previously untreated, centrally confirmed HER2-positive, stage I-IIIA invasive breast cancer regardless of hormone receptor status...
February 23, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28238551/molecular-mechanism-of-ampa-receptor-modulation-by-tarp-stargazin
#6
Anat Ben-Yaacov, Moshe Gillor, Tomer Haham, Alon Parsai, Mohammad Qneibi, Yael Stern-Bach
AMPA receptors (AMPARs) mediate the majority of fast excitatory transmission in the brain and critically contribute to synaptic plasticity and pathology. AMPAR trafficking and gating are tightly controlled by auxiliary transmembrane AMPAR regulatory proteins (TARPs). Here, using systematic domain swaps with the TARP-insensitive kainate receptor GluK2, we show that AMPAR interaction with the prototypical TARP stargazin/γ2 primarily involves the AMPAR membrane domains M1 and M4 of neighboring subunits, initiated or stabilized by the AMPAR C-tail, and that these interactions are sufficient to enable full receptor modulation...
February 17, 2017: Neuron
https://www.readbyqxmd.com/read/28238060/novel-biotechnology-approaches-in-colorectal-cancer-diagnosis-and-therapy
#7
REVIEW
Soudabeh Kavousipour, Fathemeh Khademi, Mozhdeh Zamani, Bahareh Vakili, Pooneh Mokarram
With ever-increasing molecular information about colorectal cancer (CRC), there is an expectation to detect more sensitive and specific molecular markers for new advanced diagnostic methods that can surpass the limitations of current screening tests. Moreover, enhanced molecular pathology knowledge about cancer has led to the development of targeted therapies, designed to interfere with specific aberrant biological pathways in cancer. Furthermore, biotechnology has opened a new window in CRC diagnosis and treatment by introducing different application of antibodies, antibody fragments, non-Ig scaffold proteins, and aptamers in targeted therapy and drug delivery...
February 25, 2017: Biotechnology Letters
https://www.readbyqxmd.com/read/28237514/allodynia-lowering-induced-by-cannabinoids-and-endocannabinoids-alice
#8
REVIEW
Livio Luongo, Katarzyna Starowicz, Sabatino Maione, Vincenzo Di Marzo
Neuropathic pain is a neurological disorder that strongly affects the quality of life of patients. The molecular and cellular mechanisms at the basis of the neuropathic pain establishment still need to be clarified. Among the neuromodulators involved in the pathological pain pathways, endocannabinoid system could be deeply involved in both neuronal and non-neuronal mechanisms responsible for the appearance of tactile allodynia. Indeed, the function and dysfunction of this complex system in the molecular and cellular mechanisms of chronic pain induction and maintenance has been widely studied over the last two decades...
February 22, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28237096/a-molecular-reporter-for-monitoring-autophagic-flux-in-nervous-system-in-vivo
#9
K Castillo, V Valenzuela, M Oñate, C Hetz
The relevance of autophagy in neuronal health has been extensively reported in a plethora of conditions affecting the nervous system, such as neurodegenerative diseases, cancer, diabetes, and tissue injury, where altered autophagic activity may contribute to the pathological process. Autophagy is a dynamic pathway involving the formation of a membrane surrounding and enclosing cargoes that are delivered to lysosomal compartments for degradation. Cargoes can include large protein aggregates, organelles, or even pathogens...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28236760/differential-expression-of-circular-rnas-in-glioblastoma-multiforme-and-its-correlation-with-prognosis
#10
Junle Zhu, Jingliang Ye, Lei Zhang, Lili Xia, Hongkang Hu, Heng Jiang, Zhiping Wan, Fei Sheng, Yan Ma, Wen Li, Jun Qian, Chun Luo
OBJECTIVE: The present study aimed to explore the expression profiles of circular RNAs (circRNAs) in glioblastoma multiforme (GBM) in an attempt to identify potential core genes in the pathogenesis of this tumor. METHODS: Differentially expressed circRNAs were screened between tumor tissues from five GBM patients and five normal brain samples using Illumina Hiseq. Bioinformatics analysis was used to analyze their potential function. CircBRAF was further detected in different WHO grades glioma tissues and normal brain tissues...
February 22, 2017: Translational Oncology
https://www.readbyqxmd.com/read/28236214/expanded-and-wild-type-ataxin-3-modify-the-redox-status-of-sh-sy5y-cells-overexpressing-%C3%AE-synuclein
#11
Carolina Noronha, Rita Perfeito, Mário Laço, Ullrich Wüllner, A Cristina Rego
Neurodegenerative diseases are considered to be distinct clinical entities, although they share the formation of proteinaceous aggregates and several neuropathological mechanisms. Increasing evidence suggest a possible interaction between proteins that have been classically associated to distinct neurodegenerative diseases. Thus, common molecular and cellular pathways might explain similarities between disease phenotypes. Interestingly, the characteristic Parkinson's disease (PD) phenotype linked to bradykinesia is also a clinical presentation of other neurodegenerative diseases...
February 25, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28231262/oleanolic-acid-induces-migration-in-mv1lu-and-mda-mb-231-epithelial-cells-involving-egf-receptor-and-map-kinases-activation
#12
Ángel Bernabé-García, David Armero-Barranco, Sergio Liarte, María Ruzafa-Martínez, Antonio Jesús Ramos-Morcillo, Francisco José Nicolás
During wound healing, skin function is restored by the action of several cell types that undergo differentiation, migration, proliferation and/or apoptosis. These dynamics are tightly regulated by the evolution of the extra cellular matrix (ECM) contents along the process. Pharmacologically active flavonoids have shown to exhibit useful physiological properties interesting in pathological states. Among them, oleanolic acid (OA), a pentacyclic triterpene, shows promising properties over wound healing, as increased cell migration in vitro and improved wound resolution in vivo...
2017: PloS One
https://www.readbyqxmd.com/read/28230744/s-allylmercaptocysteine%C3%A2-attenuates%C3%A2-cisplatin-induced%C3%A2-nephrotoxicity%C3%A2-through%C3%A2-suppression%C3%A2-of%C3%A2-apoptosis-%C3%A2-oxidative%C3%A2-stress-%C3%A2-and%C3%A2-inflammation
#13
Xiaosong Zhu, Xiaoyan Jiang, Ang Li, Zhongxi Zhao, Siying Li
Cisplatin is a potent chemotherapeutic agent, but its clinical usage is limited by nephrotoxicity. S-allylmercaptocysteine (SAMC), one of the water-soluble organosulfur garlic derivatives, has antioxidant and anti-inflammatory properties and plays an important role in protecting cells from apoptosis. This study aims to examine the protective effects of SAMC on cisplatin nephrotoxicity and to explore the mechanism of its renoprotection. Rats were treated with cisplatin with or without pre-treatment with SAMC...
February 20, 2017: Nutrients
https://www.readbyqxmd.com/read/28230179/crowdsourcing-scoring-of-immunohistochemistry-images-evaluating-performance-of-the-crowd-and-an-automated-computational-method
#14
Humayun Irshad, Eun-Yeong Oh, Daniel Schmolze, Liza M Quintana, Laura Collins, Rulla M Tamimi, Andrew H Beck
The assessment of protein expression in immunohistochemistry (IHC) images provides important diagnostic, prognostic and predictive information for guiding cancer diagnosis and therapy. Manual scoring of IHC images represents a logistical challenge, as the process is labor intensive and time consuming. Since the last decade, computational methods have been developed to enable the application of quantitative methods for the analysis and interpretation of protein expression in IHC images. These methods have not yet replaced manual scoring for the assessment of IHC in the majority of diagnostic laboratories and in many large-scale research studies...
February 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28230058/macrophage-migration-inhibitory-factor-is-subjected-to-glucose-modification-and-oxidation-in-alzheimer-s-disease
#15
Omar Kassaar, Marta Pereira Morais, Suying Xu, Emily L Adam, Rosemary C Chamberlain, Bryony Jenkins, Tony James, Paul T Francis, Stephen Ward, Robert J Williams, Jean van den Elsen
Glucose and glucose metabolites are able to adversely modify proteins through a non-enzymatic reaction called glycation, which is associated with the pathology of Alzheimer's Disease (AD) and is a characteristic of the hyperglycaemia induced by diabetes. However, the precise protein glycation profile that characterises AD is poorly defined and the molecular link between hyperglycaemia and AD is unknown. In this study, we define an early glycation profile of human brain using fluorescent phenylboronate gel electrophoresis and identify early glycation and oxidation of macrophage migration inhibitory factor (MIF) in AD brain...
February 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28229904/regulation-of-g-protein-coupled-receptor-signalling-underpinning-neurobiology-of-mood-disorders-and-depression
#16
Dimitris K Grammatopoulos
G-protein coupled receptors (GPCRs) have long been at the centre of investigations of the neurobiology of depression and mood disorders. Different facets of GPCR signalling pathways, including those controlling monoaminergic and neuropeptidergic hormonal systems are believed to be dysregulated in major depressive and bipolar disorders. Although these receptors are key molecular targets for a variety of therapeutic agents and continue to be the focus of intense pharmaceutical development, the molecular mechanisms activated by these GPCRs and underpin the pathological basis of mood disorders remain poorly understood...
February 13, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28229250/role-of-mirnas-in-human-disease-and-inborn-errors-of-metabolism
#17
Ana Rivera-Barahona, Belén Pérez, Eva Richard, Lourdes R Desviat
MicroRNAs (miRNAs) are short, noncoding RNAs that regulate gene expression posttranscriptionally by base pairing with target messenger RNAs (mRNAs). They are estimated to target ∼60% of all human protein-coding genes and are involved in regulating key physiological processes and intracellular signaling pathways. They also exhibit tissue specificity, and their dysregulation is linked to the progression of pathology. Identifying disease associated miRNAs and their respective targets provides novel molecular insight into disease, enabling the design of new therapeutic strategies...
February 22, 2017: Journal of Inherited Metabolic Disease
https://www.readbyqxmd.com/read/28228761/innate-immune-activity-in-glomerular-podocytes
#18
REVIEW
Hong Xia, Wenduona Bao, Shaolin Shi
Glomerular podocytes are specialized in structure and play an essential role in glomerular filtration. In addition, podocyte stress can initiate glomerular damage by inducing the injury of other glomerular cell types. Studies have shown that podocytes possess the property of immune cells and may be involved in adaptive immunity. Emerging studies have also shown that podocytes possess signaling pathways of innate immune responses and that innate immune responses often result in podocyte injury. More recently, mitochondrial-derived damage-associated molecular patterns (mtDAMPs) have been shown to play a critical role in a variety of pathological processes in cells...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28228347/effect-of-hyaluronic-acid-on-the-regulation-of-inflammatory-mediators-in-osteoarthritis-of-the-temporomandibular-joint-a-systematic-review
#19
REVIEW
V Iturriaga, T Bornhardt, C Manterola, P Brebi
Osteoarthritis is one of the most frequent pathologies affecting the temporomandibular joint (TMJ). There is evidence that the use of intra-articular hyaluronic acid (HA) for the treatment of this disorder achieves positive effects through a reduction in inflammatory mediators. A systematic review of the available evidence regarding the regulation of inflammatory mediators when applying HA in osteoarthritis of the TMJ in humans was performed. The Web of Science, Embase, ScienceDirect, MEDLINE, Scopus, EBSCOhost, and LILACS databases, SciELO library, and search engine Trip Database were searched systematically...
February 19, 2017: International Journal of Oral and Maxillofacial Surgery
https://www.readbyqxmd.com/read/28228131/whole-genome-sequencing-of-one-complex-pedigree-illustrates-challenges-with-genomic-medicine
#20
Han Fang, Yiyang Wu, Hui Yang, Margaret Yoon, Laura T Jiménez-Barrón, David Mittelman, Reid Robison, Kai Wang, Gholson J Lyon
BACKGROUND: Human Phenotype Ontology (HPO) has risen as a useful tool for precision medicine by providing a standardized vocabulary of phenotypic abnormalities to describe presentations of human pathologies; however, there have been relatively few reports combining whole genome sequencing (WGS) and HPO, especially in the context of structural variants. METHODS: We illustrate an integrative analysis of WGS and HPO using an extended pedigree, which involves Prader-Willi Syndrome (PWS), hereditary hemochromatosis (HH), and dysautonomia-like symptoms...
February 23, 2017: BMC Medical Genomics
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