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https://www.readbyqxmd.com/read/29243911/neurodegenerative-disease-proteinopathies-are-connected-to-distinct-histone-post-translational-modification-landscapes
#1
Karen Chen, Seth A Bennett, Navin Rana, Huda Yousuf, Mohamed Said, Sadiqa Taaseen, Natalie Mendo, Steven Marc Meltser, Mariana Torrente
Amyotrophic Lateral Sclerosis (ALS) and Parkinson's disease (PD) are devastating neurodegenerative diseases involving the progressive degeneration of neurons. No cure is available for patients diagnosed with these diseases. A prominent feature for both ALS and PD is the accumulation of protein inclusions in the cytoplasm of degenerating neurons; however, the particular protein comprising these inclusions varies. The RNA-binding proteins TDP-43 and FUS are most notable in ALS, while α-synuclein aggregates into Lewy bodies in PD...
December 15, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29243812/dysregulated-mitogen-activated-protein-kinase-signalling-as-an-oncogenic-basis-for-clear-cell-sarcoma-of-the-kidney
#2
Colin Kenny, Naomi McDonagh, Antonio Lazaro, Elaine O'Meara, Rut Klinger, Darran O'Connor, Fiona Roche, Karsten Hokamp, Maureen J O'Sullivan
The oncogenic mechanisms and tumour biology underpinning Clear Cell Sarcoma of Kidney (CCSK), the second commonest paediatric renal malignancy, are poorly understood and currently therapy depends heavily on doxorubicin with cardiotoxic side-effects. Previously, we characterised the balanced t(10;17)(q22;p13) chromosomal translocation, identified at that time as the only recurrent genetic aberration in CCSK. This translocation results in an in-frame fusion of the genes YWHAE (encoding 14-3-3ε)and NUTM2, with a somatic incidence of 12%...
December 15, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/29243807/microrna-as-a-systemic-intervention-in-the-specific-breast-cancer-subtypes-with-c-myc-impacts-introducing-subtype-based-appraisal-tool
#3
REVIEW
Vida Pourteimoor, Mahdi Paryan, Samira Mohammadi-Yeganeh
Breast cancer is indisputably a heterogeneous disease, in which a formidable combination of definitely dis-regulated C-MYC and microRNA (miRNA) profiles along with other factors are responsible to generate a specific type of breast cancer. C-MYC as a master regulator of more than 20,000 genes can modify the expression of genes underlying to perform diverse conflicting functional frameworks. The functional spectra of miRNA in the new areas of the evolution of cell behaviors are identified. Here, we endeavor to summarize some recent advances of miRNA applications that can be recruited as combinatorial targeted therapy for patients with breast cancer...
December 15, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29243047/role-of-%C3%AE-catenin-in-cisplatin-resistance-relapse-and-prognosis-of-head-and-neck-squamous-cell-carcinoma
#4
Souvick Roy, Madhabananda Kar, Shomereeta Roy, Arka Saha, Swatishree Padhi, Birendranath Banerjee
BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is one of the most common types of cancer in India with high incidence and rapid recurrence rates. Here, we aimed to investigate the role of β-catenin, a developmental pathway gene, in HNSCC therapy resistance, DNA damage response, recurrence and prognosis. METHODS: In total 80 HNSCC samples were included. Western blot, immunohistochemistry and qRT-PCR analyses were performed to assess β-catenin expression in the cut margin and tumor areas of each sample...
December 14, 2017: Cellular Oncology (Dordrecht)
https://www.readbyqxmd.com/read/29243020/effect-of-1064-nm-q-switched-nd-yag-laser-on-invasiveness-and-innate-immune-response-in-keratinocytes-infected-with-candida-albicans
#5
Baroni Adone, De Filippis Anna, Oliviero Giovanni, Fusco Alessandra, Perfetto Brunella, Buommino Elisabetta, Donnarumma Giovanna
Candida albicans is an opportunistic pathogen commensal in the oral cavity, vagina, and healthy skin. Common therapeutic options for fungal infections are topical or systemic antifungal drugs. Recently, in cutaneous pathologies, lasers and light-based treatments have emerged showing few contraindications and minimal side effects. The Q-switched (Nd-YAG) laser at a wavelength of 1064 nm has been shown to be useful in dermatology, dentistry, and some other medical specialties. It is used to treat onychomycoses, warts, and wounds and in some other treatments...
December 14, 2017: Lasers in Medical Science
https://www.readbyqxmd.com/read/29242835/characterization-of-the-mechanisms-of-daptomycin-resistance-among-gram-positive-bacterial-pathogens-by-multidimensional-lipidomics
#6
Kelly M Hines, Adam Waalkes, Kelsi Penewit, Elizabeth A Holmes, Stephen J Salipante, Brian J Werth, Libin Xu
Previous work suggests that altered lipid metabolism may be associated with daptomycin resistance in Gram-positive pathogens, but lipidomic changes underlying resistance are not fully understood. We performed untargeted lipidomics by using three-dimensional hydrophilic interaction liquid chromatography-ion mobility-mass spectrometry (HILIC-IM-MS) to characterize alterations in the lipidomes of daptomycin-susceptible and -resistant isogenic strain pairs of Enterococcus faecalis, Staphylococcus aureus, and Corynebacterium striatum...
November 2017: MSphere
https://www.readbyqxmd.com/read/29242642/targeting-mutant-p53-for-efficient-cancer-therapy
#7
REVIEW
Vladimir J N Bykov, Sofi E Eriksson, Julie Bianchi, Klas G Wiman
The tumour suppressor gene TP53 is the most frequently mutated gene in cancer. Wild-type p53 can suppress tumour development by multiple pathways. However, mutation of TP53 and the resultant inactivation of p53 allow evasion of tumour cell death and rapid tumour progression. The high frequency of TP53 mutation in tumours has prompted efforts to restore normal function of mutant p53 and thereby trigger tumour cell death and tumour elimination. Small molecules that can reactivate missense-mutant p53 protein have been identified by different strategies, and two compounds are being tested in clinical trials...
December 15, 2017: Nature Reviews. Cancer
https://www.readbyqxmd.com/read/29242405/digitalis-like-compounds-restore-hnis-expression-and-iodide-uptake-capacity-in-anaplastic-thyroid-cancer
#8
Marika H Tesselaar, Thomas Crezee, Imke Schuurmans, Danny Gerrits, James Nagarajah, Otto C Boerman, Ilse van Engen-van Grunsven, Johannes W A Smit, Romana T Netea-Maier, Theo S Plantinga
Purpose: Anaplastic thyroid cancer (ATC) is a rare malignancy that accounts for 1-2% of all thyroid cancers. ATC is one of the most aggressive human cancers, with rapid growth, tumor invasion and development of distant metastases. The median survival is only 5 months and the 1-year survival is less than 20%. Moreover, as a result of severe dedifferentiation including the loss of human sodium iodide symporter (hNIS) expression, radioactive iodide (RAI) therapy is ineffective. Recently, we have demonstrated beneficial effects of autophagy activating digitalis-like compounds (DLCs) on redifferentiation and concomitant restoration of iodide uptake in RAI-refractory papillary and follicular thyroid cancer cell lines...
December 14, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/29242214/expressed-gene-fusions-as-frequent-drivers-of-poor-outcomes-in-hormone-receptor-positive-breast-cancer
#9
Karina J Matissek, Maristela L Onozato, Sheng Sun, Zongli Zheng, Andrew Schultz, Jesse Lee, Kristofer Patel, Piiha-Lotta Jerevall, Srinivas V Saladi, Allison MacLeay, Mehrad Tavallai, Tanja Badovinac-Crnjevic, Carlos Barrios, Nuran Beşe, Arlene Chan, Yanin Chavarri-Guerra, Marcio Debiasi, Elif Demirdogen, Unal Egeli, Sehsuvar Gökgöz, Henry Gomez, Pedro Liedke, Ismet Tasdelen, Sahsine Tolunay, Gustavo Werutsky, Jessica St Louis, Nora Horick, Dianne M Finkelstein, Long Phi Le, Aditya Bardia, Paul E Goss, Dennis C Sgroi, A John Iafrate, Leif W Ellisen
We sought to uncover novel genetic drivers of hormone-receptor positive (HR+) breast cancer, employing a targeted next-generation sequencing approach for detecting expressed gene rearrangements without prior knowledge of the fusion partners. We identified intergenic fusions involving driver genes including PIK3CA, AKT3, RAF1 and ESR1 in 14% (24/173) of unselected patients with advanced HR+ breast cancer. Fluorescence in situ hybridization (FISH) confirmed the corresponding chromosomal rearrangements in both primary and metastatic tumors...
December 14, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/29242210/reversible-immortalisation-enables-genetic-correction-of-human-muscle-progenitors-and-engineering-of-next-generation-human-artificial-chromosomes-for-duchenne-muscular-dystrophy
#10
Sara Benedetti, Narumi Uno, Hidetoshi Hoshiya, Martina Ragazzi, Giulia Ferrari, Yasuhiro Kazuki, Louise Anne Moyle, Rossana Tonlorenzi, Angelo Lombardo, Soraya Chaouch, Vincent Mouly, Marc Moore, Linda Popplewell, Kanako Kazuki, Motonobu Katoh, Luigi Naldini, George Dickson, Graziella Messina, Mitsuo Oshimura, Giulio Cossu, Francesco Saverio Tedesco
Transferring large or multiple genes into primary human stem/progenitor cells is challenged by restrictions in vector capacity, and this hurdle limits the success of gene therapy. A paradigm is Duchenne muscular dystrophy (DMD), an incurable disorder caused by mutations in the largest human gene: dystrophin. The combination of large-capacity vectors, such as human artificial chromosomes (HACs), with stem/progenitor cells may overcome this limitation. We previously reported amelioration of the dystrophic phenotype in mice transplanted with murine muscle progenitors containing a HAC with the entire dystrophin locus (DYS-HAC)...
December 14, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/29241731/efficacy-of-lentiviral-mediated-gene-therapy-in-an-omenn-syndrome-rag2-mouse-model-is-not-hindered-by-inflammation-and-immune-dysregulation
#11
Valentina Capo, Maria Carmina Castiello, Elena Fontana, Sara Penna, Marita Bosticardo, Elena Draghici, Luigi P Poliani, Lucia Sergi Sergi, Rosita Rigoni, Barbara Cassani, Monica Zanussi, Paola Carrera, Paolo Uva, Kerry Dobbs, Nicolò Sacchetti, Luigi D Notarangelo, Niek P van Til, Gerard Wagemaker, Anna Villa
BACKGROUND: Omenn syndrome (OS) is a rare severe combined immunodeficiency associated with autoimmunity, caused by defects of the lymphoid-specific V(D)J recombination. Most patients carry hypomorphic mutations in recombination activating genes (RAG) 1 or 2. Hematopoietic stem cell (HSC) transplantation is the standard treatment, however gene therapy (GT) may represent a valid alternative, especially for patients lacking a matched donor. OBJECTIVE: To determine the efficacy of lentiviral vector (LV) mediated GT in the murine model of OS (Rag2R229Q/R229Q) in correcting immunodeficiency and autoimmunity...
December 11, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29241457/impaired-regeneration-in-calpain-3-null-muscle-is-associated-with-perturbations-in-mtorc1-signaling-and-defective-mitochondrial-biogenesis
#12
Mehmet E Yalvac, Jakkrit Amornvit, Cilwyn Braganza, Lei Chen, Syed-Rehan A Hussain, Kimberly M Shontz, Chrystal L Montgomery, Kevin M Flanigan, Sarah Lewis, Zarife Sahenk
BACKGROUND: Previous studies in patients with limb-girdle muscular dystrophy type 2A (LGMD2A) have suggested that calpain-3 (CAPN3) mutations result in aberrant regeneration in muscle. METHODS: To gain insight into pathogenesis of aberrant muscle regeneration in LGMD2A, we used a paradigm of cardiotoxin (CTX)-induced cycles of muscle necrosis and regeneration in the CAPN3-KO mice to simulate the early features of the dystrophic process in LGMD2A. The temporal evolution of the regeneration process was followed by assessing the oxidative state, size, and the number of metabolic fiber types at 4 and 12 weeks after last CTX injection...
December 14, 2017: Skeletal Muscle
https://www.readbyqxmd.com/read/29241367/differentiation-of-conjunctiva-mesenchymal-stem-cells-into-secreting-islet-beta-cells-on-plasma-treated-electrospun-nanofibrous-scaffold
#13
Samad Nadri, Ghasem Barati, Hossein Mostafavi, Abdolreza Esmaeilzadeh, Seyed Ehsan Enderami
Transplantation of stem cells using biocompatible nanofibrous scaffolds is a promising therapeutic method for treating Diabetic Mellitus. The aim of this study was to derive insulin-producing cells (IPCs) from conjunctiva-derived mesenchymal stem cell (CJMSCs) and to compare the functionality of differentiated IPCs in a three-dimensional (3D) culture with 2D. Furthermore, the effects of hydrophobicity of scaffold on IPCs differentiation were examined. Scanning electron microscopy (SEM), quantitative real times PCR (qPCR), Immunostaining and flow cytometry were used to analyze fabricated scaffold and the presence of IPCs...
December 14, 2017: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/29240916/study-on-the-anti-endotoxin-effect-of-sinomenine-using-an-agilent-genome-array
#14
Yiyi Hu, Bin Li, Libin Wen, Kongwang He
Background: Endotoxin is a significant contributing factor underlying the occurrence of fever, diarrhea, inflammation, edema, coagulation, shock, and other syndromes associated with Gram-negative bacterial infections. To date, there is no effective treatment for endotoxemia. Aim: The aim of this study was to characterize differentially expressed genes in sinomenine-treated and LPS-induced endothelial cells by microarray analysis, and to determine the potential pharmacological activity of sinomenine...
December 12, 2017: QJM: Monthly Journal of the Association of Physicians
https://www.readbyqxmd.com/read/29240584/dermatofibrosarcoma-protuberans-of-distal-extremities-and-acral-sites-a-clinicopathologic-analysis-of-27-cases
#15
Kabeer K Shah, Jonathan B McHugh, Andrew L Folpe, Rajiv M Patel
Dermatofibrosarcoma protuberans (DFSP) of the distal extremities and acral sites are extremely rare and incompletely characterized. Twenty-seven DFSP occurring in these sites were retrieved from our collective archives and reevaluated. Tumors occurred in 16 males and 11 females. Median age at presentation was 42.5 years (range, 7 to 78 y). Lesions involved the foot (18 with 6 in the toes and 2 on the plantar foot), distal ankle (4), hand (4 with 2 in the thumbs), and wrist (1). All cases showed predominantly classic DFSP morphology and were diffusely CD34 positive...
December 7, 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/29239897/ex-vivo-expression-of-chemokine-receptors-on-cells-surrounding-cutaneous-nerves-in-patients-with-hiv-associated-sensory-neuropathy
#16
Jenjira Mountford, Fitri Octaviana, Riwanti Estiasari, Denise Dewanto Setiawan, Ibnu Ariyanto, Silvia Lee, Jessica Gaff, Constance Chew, Connie Jackaman, Peter Kamerman, Catherine Cherry, Patricia Price
OBJECTIVE: HIV-associated sensory neuropathy (HIV-SN) remains common in HIV+ individuals receiving anti-retroviral therapy (ART), even though neurotoxic anti-retroviral drugs (e.g. stavudine) have been phased out of use. Accumulating evidence indicates that the neuropathy is immune-mediated. We hypothesise that chemokines produced locally in the skin promote migration of macrophages and T-cells into the tissue, damaging cutaneous nerves causing HIV-SN. DESIGN: We assessed chemokine receptor expression on infiltrating CD14 and CD3 cells around cutaneous nerves in standardised skin biopsies from HIV-SN+ patients (n = 5), HIV-SN- patients (n = 9) and healthy controls (n = 4)...
December 12, 2017: AIDS
https://www.readbyqxmd.com/read/29239333/nigral-dopaminergic-neuron-replenishment-in-adult-mice-through-ve-cadherin-expressing-neural-progenitor-cells
#17
Abir A Rahman, Nathan K Lai, Joshua E Albright, Paige E Urquhart, Abby R Webb, Brad E Morrison
The function of dopaminergic neurons in the substantia nigra is of central importance to the coordination of movement by the brain's basal ganglia circuitry. This is evidenced by the loss of these neurons, resulting in the cardinal motor deficits associated with Parkinson's disease. In order to fully understand the physiology of these key neurons and develop potential therapies for their loss, it is essential to determine if and how dopaminergic neurons are replenished in the adult brain. Recent work has presented evidence for adult neurogenesis of these neurons by Nestin+/Sox2- neural progenitor cells...
November 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/29239102/serpinh1-overexpression-in-clear-cell-renal-cell-carcinoma-association-with-poor-clinical-outcome-and-its-potential-as-a-novel-prognostic-marker
#18
Yijun Qi, Yue Zhang, Zhiqiang Peng, Lei Wang, Kaizhen Wang, Duiping Feng, Junqi He, Junfang Zheng
Precision therapy for clear cell renal cell carcinoma (ccRCC) requires molecular biomarkers ascertaining disease prognosis. In this study, we performed integrated proteomic and transcriptomic screening in all four tumour-node-metastasis stages of ccRCC and adjacent normal tissues (n = 18) to investigate differentially expressed genes. Most identified differentially expressed genes revealed a strong association with transforming growth factor-β level and the epithelial-to-mesenchymal transition process. Of them, Serpin peptidase inhibitor clade H member 1 (SERPINH1) revealed the strongest association with poor prognosis and regulation on the expression levels of epithelial-to-mesenchymal transition markers...
December 14, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29239062/gvhd-amelioration-by-human-bone-marrow-mesenchymal-stromal-stem-cell-derived-extracellular-vesicles-is-associated-with-peripheral-preservation-of-naive-t-cell-populations
#19
Sumie Fujii, Yasuo Miura, Aya Fujishiro, Takero Shindo, Yutaka Shimazu, Hideyo Hirai, Hidetoshi Tahara, Akifumi Takaori-Kondo, Tatsuo Ichinohe, Taira Maekawa
A substantial proportion of patients with acute graft-versus-host disease (aGVHD) respond to cell therapy with culture-expanded human bone marrow mesenchymal stromal/stem cells (BM-MSCs). However, the mechanisms by which these cells can ameliorate aGVHD-associated complications remain to be clarified. We show here that BM-MSC-derived extracellular vesicles (EVs) recapitulated the therapeutic effects of BM-MSCs against aGVHD. Systemic infusion of human BM-MSC-derived EVs prolonged the survival of mice with aGVHD and reduced the pathologic damage in multiple GVHD-targeted organs...
December 14, 2017: Stem Cells
https://www.readbyqxmd.com/read/29238626/c-kit-positive-cardiac-outgrowth-cells-demonstrate-better-ability-for-cardiac-recovery-against-ischemic-myopathy
#20
Chuan Li, Satoshi Matsushita, Zhengqing Li, Jianjun Guan, Atsushi Amano
Objective: Resident cardiac stem cells are expected to be a therapeutic option for patients who suffer from severe heart failure. However, uncertainty remains over whether sorting cells for c-kit, a stem cell marker, improves therapeutic outcomes. Materials and methods: Cardiac outgrowth cells cultured from explants of rat heart atrium were sorted according to their positivity (+) or negativity (-) for c-kit. These cells were exposed to hypoxia for 3 d, and subsequently harvested for mRNA expression measurement...
October 2017: Journal of Stem Cell Research & Therapy
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