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https://www.readbyqxmd.com/read/29228445/the-protective-effect-and-its-mechanism-of-3-n-butylphthalide-pretreatment-on-cerebral-ischemia-reperfusion-injury-in-rats
#1
R-Y Yan, S-J Wang, G-T Yao, Z-G Liu, N Xiao
OBJECTIVE: To investigate the potential effect of 3-n-butylphthalide (NBP) pretreatment on the cerebral ischemia/reperfusion injury in rats and the relevant mechanism. MATERIALS AND METHODS: A total of 90 rats was divided into three groups: Sham operation group (Sham group), ischemia-reperfusion group (I-R group), and NBP pretreatment group (NBP group 75 mg·kg-1·d-1 gavage). Pre-treatment was given once a day within 1 week before establishing the rat model of cerebral ischemia-reperfusion injury...
November 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29228429/peripheral-blood-cd8-t-cell-profiles-in-patients-with-psoriatic-arthritis-a-cross-sectional-case-control-study
#2
E Colombo, G Galleri, G L Erre, C Piras, G Biondi, L Taras, A Zinellu, A A Mangoni, R Manetti, M Montesu, G Passiu
OBJECTIVE: While CD4+ T-cells are traditionally regarded as the main pathogenic T-cell subpopulation in psoriatic arthritis (PsA), the role of circulating CD8+ T-cells remains poorly characterized. We evaluated the differential representation of CD8+ T-cell subpopulations in peripheral blood (PB) of PsA patients. PATIENTS AND METHODS: CD8+IL-17+, CD8+IFNγ+ and CD8+IL-17-IL-22+ T-cells were evaluated by flow-cytometry in 25 consecutive PsA patients, 7 rheumatoid arthritis (RA) patients, 16 patients with psoriasis, and 26 healthy controls (HC)...
November 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29228368/the-oncolytic-virus-mg1-targets-and-eliminates-latently-hiv-1-infected-cells-implications-for-an-hiv-cure
#3
Nischal Ranganath, Teslin S Sandstrom, Stephanie C Burke Schinkel, Sandra C Côté, Jonathan B Angel
Latently HIV-infected cells evade immune- and drug-mediated clearance. These cells harbour intracellular signalling defects including impairment of the antiviral, type I IFN (IFN-I) response. Such defects have also been observed in several cancers, and have been exploited for the development of therapeutic oncolytic viruses, including the recombinant Maraba virus (MG1). We therefore hypothesized that MG1 would infect and eliminate latently HIV-1-infected cells, while sparing healthy uninfected cells. Preferential infection and elimination by MG1 was first demonstrated in latently HIV-1-infected cell lines...
December 8, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29228364/age-dependent-changes-in-mean-and-variance-of-gene-expression-across-tissues-in-a-twin-cohort
#4
Ana Viñuela, Andrew A Brown, Alfonso Buil, Pei-Chien Tsai, Matthew N Davies, Jordana T Bell, Emmanouil T Dermitzakis, Timothy D Spector, Kerrin S Small
Changes in mean and variance of gene expression with age have consequences for healthy aging and disease development. Age-dependent changes in phenotypic variance have been associated to a decline in regulatory functions leading to increase in disease risk. Here we investigate age-related mean and variance changes in gene expression measured by RNA-seq of fat, skin, whole blood and derived lymphoblastoid cell lines (LCLs) expression from 855 adult female twins. We see evidence of up to 60% of age effects on transcription levels shared across tissues, and 47% of those on splicing...
December 8, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/29228356/dietary-intervention-rescues-myopathy-associated-with-neurofibromatosis-type-1
#5
Matthew A Summers, Thusitha Rupasinghe, Emily R Vasiljevski, Frances J Evesson, Kathy Mikulec, Lauren Peacock, Kate Gr Quinlan, Sandra T Cooper, Ute Roessner, David A Stevenson, David G Little, Aaron Schindeler
Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disorder with complex symptomology. In addition to a predisposition to tumors, children with NF1 can present with reduced muscle mass, global muscle weakness, and impaired motor skills, which can have a significant impact on quality of life. Genetic mouse models have shown a lipid storage disease phenotype may underlie muscle weakness in NF1. Herein we confirm that biopsy specimens from six individuals with NF1 similarly manifest features of a lipid storage myopathy, with marked accumulation of intramyocellular lipid, fibrosis, and mononuclear cell infiltrates...
December 8, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/29228301/targeted-inhibition-of-janus-kinases-abates-interfon-gamma-induced-invasive-behaviour-of-fibroblast-like-synoviocytes
#6
Thomas Karonitsch, Denise Beckmann, Karolina Dalwigk, Birgit Niederreiter, Paul Studenic, Ruth A Byrne, Johannes Holinka, Florian Sevelda, Adelheid Korb-Pap, Günter Steiner, Josef S Smolen, Thomas Pap, Hans P Kiener
Objectives: The aim was to explore the function of the T-cell cytokine IFNγ for mesenchymal tissue remodelling in RA and to determine whether IFNγ signalling controls the invasive potential of fibroblast-like synoviocytes (FLS). Methods: To assess architectural responses, FLS were cultured in three-dimensional micromasses. FLS motility was analysed in migration and invasion assays. Signalling events relevant to cellular motility were defined by western blots. Baricitinib and small interfering RNA pools were used to suppress Janus kinase (JAK) functions...
December 7, 2017: Rheumatology
https://www.readbyqxmd.com/read/29228279/in-vitro-model-of-fully-differentiated-human-nasal-epithelial-cells-infected-with-rhinovirus-reveals-epithelium-initiated-immune-responses
#7
Kai Sen Tan, Hsiao Hui Ong, Yan Yan, Jing Liu, Chunwei Li, Yew Kwang Ong, Kim Thye Thong, Hyung Won Choi, De-Yun Wang, Vincent T Chow
Human rhinoviruses (HRVs) are the commonest cause of the common cold. While less pathogenic compared to other respiratory viruses, it is frequently associated with exacerbation of chronic respiratory diseases such as rhinosinusitis and asthma exacerbation. Currently, there are limited studies on HRV infection of nasal epithelial cells despite being the first site of viral contact, immune initiation, and airway inter-connectivity. Hence, we established a model of HRV infection of in vitro differentiated human nasal epithelial cells (hNECs) derived from multiple individuals...
December 8, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29228214/oestrogen-receptor-%C3%AE-ligand-acts-on-cd11c-cells-to-mediate-protection-in-experimental-autoimmune-encephalomyelitis
#8
Roy Y Kim, Darian Mangu, Alexandria S Hoffman, Rojan Kovash, Eunice Jung, Noriko Itoh, Rhonda Voskuhl
Oestrogen treatments are neuroprotective in a variety of neurodegenerative disease models. Selective oestrogen receptor modifiers are needed to optimize beneficial effects while minimizing adverse effects to achieve neuroprotection in chronic diseases. Oestrogen receptor beta (ERβ) ligands are potential candidates. In the multiple sclerosis model chronic experimental autoimmune encephalomyelitis, ERβ-ligand treatment is neuroprotective, but mechanisms underlying this neuroprotection remain unclear. Specifically, whether there are direct effects of ERβ-ligand on CD11c+ microglia, myeloid dendritic cells or macrophages in vivo during disease is unknown...
December 8, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29228211/asymmetry-of-post-mortem-neuropathology-in-behavioural-variant-frontotemporal-dementia
#9
David J Irwin, Corey T McMillan, Sharon X Xie, Katya Rascovsky, Vivianna M Van Deerlin, H Branch Coslett, Roy Hamilton, Geoffrey Aguirre, Edward B Lee, Virginia M Y Lee, John Q Trojanowski, Murray Grossman
Antemortem behavioural and anatomic abnormalities have largely been associated with right hemisphere disease in behavioural-variant frontotemporal dementia, but post-mortem neuropathological examination of bilateral hemispheres remains to be defined. Here we measured the severity of post-mortem pathology in both grey and white matter using a validated digital image analysis method in four cortical regions sampled from each hemisphere in 26 patients with behavioural-variant frontotemporal dementia, including those with frontotemporal degeneration (i...
December 8, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29228157/gut-epithelial-vitamin-d-receptor-regulates-microbiota-dependent-mucosal-inflammation-by-suppressing-intestinal-epithelial-cell-apoptosis
#10
Lei He, Tianjing Liu, Yongyan Shi, Feng Tian, Huiyuan Hu, Dilip K Deb, Yinyin Chen, Marc Bissonnette, Yan Chun Li
Recent studies show that colonic vitamin D receptor (VDR) signaling protects the mucosal epithelial barrier and suppresses colonic inflammation, but the underlying molecular mechanism remains to be fully understood. To investigate the implication of colonic VDR down-regulation seen in patients with inflammatory bowel disease, we assessed the effect of gut epithelial VDR deletion on colonic inflammatory responses in an experimental colitis model. In 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis model, mice carrying VDR deletion in gut epithelial cells (VDRf/f;Villin-Cre or VDRΔIEC) or in colonic epithelial cells (VDRf/f;CDX2-Cre or VDRΔCEC) developed more severe clinical colitis than VDRf/f control mice, characterized by more robust TH1 and TH17 responses, with greater increases in mucosal IFN-γ+, IL-17+ and IFN-γ+IL-17+ T cells...
December 7, 2017: Endocrinology
https://www.readbyqxmd.com/read/29228112/xenotransplantation-the-current-status-and-prospects
#11
D K C Cooper, R Gaston, D Eckhoff, J Ladowski, T Yamamoto, L Wang, H Iwase, H Hara, M Tector, A J Tector
Introduction: There is a continuing worldwide shortage of organs from deceased human donors for transplantation into patients with end-stage organ failure. Genetically engineered pigs could resolve this problem, and could also provide tissues and cells for the treatment of conditions such as diabetes, Parkinson's disease and corneal blindness. Sources of data: The current literature has been reviewed. Areas of agreement: The pathobiologic barriers are now largely defined...
December 8, 2017: British Medical Bulletin
https://www.readbyqxmd.com/read/29228106/proteomics-analysis-of-good-and-poor-quality-human-sperm-demonstrates-several-proteins-are-routinely-aberrantly-regulated
#12
J K Netherton, L Hetherington, R A Ogle, T Velkov, M A Baker
Male infertility is a complex condition, and for the most part, all men produce defective spermatozoa, but infertile men have a tendency to produce more. Despite attempts to classify infertility, there is no definitive test. One approach would be to use protein biomarkers, however as yet, we still do not understand proteins that are differentially expressed within defective spermatozoa. As such, we took nine men (fertility status unknown) and used Percoll density gradients to isolate a population of good and poor quality sperm...
December 7, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/29228031/transcriptional-profiling-of-pbmcs-unravels-b-cell-mediated-immunopathogenic-imprints-of-hcv-vasculitis
#13
Emily Comstock, Cheol-Woo Kim, Alison Murphy, Benjamin Emmanuel, Xi Zhang, Michael Sneller, Bhawna Poonia, Shyamasundaran Kottilil
B cell depletion therapy using rituximab has been shown to be effective in achieving remission in patients with HCV-mixed cryoglobulinemic (MC) vasculitis. Previously, we have demonstrated abnormalities in peripheral immune cells involving neutrophils, chemotaxis, and innate immune activation among patients with HCV-MC vasculitis when compared to HCV patients without vasculitis. In this study, we evaluated the effect of B cell depletion therapy on transcriptional profiles of peripheral blood mononuclear cells before and after riruximab therapy, in order to unravel the pathogenic mechanism involved in HCV-MC vasculitis induced by abnormal B cell proliferation...
2017: PloS One
https://www.readbyqxmd.com/read/29228015/development-of-an-iron-selective-antioxidant-probe-with-protective-effects-on-neuronal-function
#14
Olimpo García-Beltrán, Natalia P Mena, Pabla Aguirre, Germán Barriga-González, Antonio Galdámez, Edgar Nagles, Tatiana Adasme, Cecilia Hidalgo, Marco T Núñez
Iron accumulation, oxidative stress and calcium signaling dysregulation are common pathognomonic signs of several neurodegenerative diseases, including Parkinson´s and Alzheimer's diseases, Friedreich ataxia and Huntington's disease. Given their therapeutic potential, the identification of multifunctional compounds that suppress these damaging features is highly desirable. Here, we report the synthesis and characterization of N-(1,3-dihydroxy-2-(hydroxymethyl)propan-2-yl)-2-(7-hydroxy-2-oxo-2H-chromen-4-yl)acetamide, named CT51, which exhibited potent free radical neutralizing activity both in vitro and in cells...
2017: PloS One
https://www.readbyqxmd.com/read/29228007/conjugation-of-nitrated-acetaminophen-to-der-p1-amplifies-peripheral-blood-monocyte-response-to-der-p1
#15
Ryan G Thomas, Brenda M Rivera Reyes, Benjamin M Gaston, Nelki B Rivera Acosta, Ilya R Bederman, Laura A Smith, Morgan T Sutton, Benlian Wang, John F Hunt, Tracey L Bonfield
BACKGROUND: An association of acetaminophen use and asthma was observed in the International Study of Asthma and Allergies in Childhood study. However there are no clear mechanisms to explain an association between acetaminophen use and immunologic pathology. In acidic conditions like those in the stomach and inflamed airway, tyrosine residues are nitrated by nitrous and peroxynitrous acids. The resulting nitrotyrosine is structurally similar to 2,4-dinitrophenol and 2,4-dinitrochlorobenzene, known haptens that enhance immune responses by covalently binding proteins...
2017: PloS One
https://www.readbyqxmd.com/read/29227868/systemic-mastocytosis-associates-with-cardiovascular-events-despite-lower-plasma-lipid-levels
#16
Swasti Indhirajanti, Paul L A van Daele, Sven Bos, Monique T Mulder, Ilze Bot, Jeanine E Roeters van Lennep
BACKGROUND AND AIMS: Mast cells have been implicated in the development and progression of atherosclerosis in animal models and human autopsy studies. However, it is unknown whether long-term exposure to excess of mast cells is associated with cardiovascular disease (CVD) in humans. Our objective was to compare the prevalence of CVD and cardiovascular risk factors in patients with systemic mastocytosis (SM) and controls. METHODS: In 50 patients with SM and 50 age and sex matched controls, the history of CVD and presence of cardiovascular risk factors were assessed...
December 8, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/29227812/overexpression-of-arginase-1-is-linked-to-dnmt3a-and-tet2-mutations-in-lower-grade-myelodysplastic-syndromes-and-chronic-myelomonocytic-leukemia
#17
A H Cull, D Mahendru, B Snetsinger, D Good, K Tyryshkin, A Chesney, Z Ghorab, M Reis, R Buckstein, R A Wells, M J Rauh
Immune dysregulation is a common feature of myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML), particularly in early stages. However, the genetic basis remains poorly understood. We recently reported that macrophages from mice deficient in tet methylcytosine dioxygenase 2 (Tet2), a model of MDS/CMML, are hyperinflammatory and have increased expression of arginase 1 (Arg1). In macrophages and myeloid derived suppressor cells (MDSCs) expression of Arg1 contributes to T-cell suppression and immune evasion by L-arginine depletion, in the setting of chronic inflammation and cancer...
December 6, 2017: Leukemia Research
https://www.readbyqxmd.com/read/29227750/genetic-polymorphisms-in-prm1-prm2-and-ybx2-genes-are-associated-with-male-factor-infertility
#18
Oya Sena E Aydos, Yalda Hekmatshoar, Buket Altınok, Tülin Özkan, Onur Şakirağaoğlu, Aynur Karadağ, Fuat Kaplan, Seda Ilgaz, Mehmet Taşpınar, Işıl Yükselen, Asuman Sunguroğlu, Kaan Aydos
AIMS: The etiology of infertility is still unknown in almost half of all male infertility patients. In sperm, DNA condensation differs from somatic and female gamete cells, with the protamine (PRM) gene and its transcription factor, Y-box binding protein 2 (YBX2), playing key roles in making the structure more compact. Protamine polymorphisms have been studied in different populations, but various results have been acquired. MATERIALS AND METHODS: In our study, we examined, for the first time in a Turkish population, the association between protamine gene alleles (PRM1 c...
December 11, 2017: Genetic Testing and Molecular Biomarkers
https://www.readbyqxmd.com/read/29227722/glucose-phosphate-isomerase-gpi-tadikonda-characterization-of-a-novel-pro340ser-mutation
#19
Ahmar U Zaidi, Prabhakar Kedar, Prasad Rao Koduri, Gerard W Goyette, Steven Buck, Donald E Paglia, Yaddanapudi Ravindranath
After a thirty-year lag, we serendipitously reestablished contact with a patient with glucose phosphate isomerase deficiency and hydrops fetalis first reported in 1987. We now provide a clinical update and provide results of mutation analysis in this patient, from Southern India. The patient now an adult female of 36 years of age has moderate anemia but requires no transfusions except with some intercurrent illnesses. Exome sequencing studies showed a homozygous c.1018C>T (Pro340Ser) mutation in exon 12 of the glucose phosphate isomerase gene and later confirmed by direct sequencing...
December 11, 2017: Pediatric Hematology and Oncology
https://www.readbyqxmd.com/read/29227715/human-papillomavirus-genome-integration-and-head-and-neck-cancer
#20
L M Pinatti, H M Walline, T E Carey
We conducted a critical review of human papillomavirus (HPV) integration into the host genome in oral/oropharyngeal cancer, reviewed the literature for HPV-induced cancers, and obtained current data for HPV-related oral and oropharyngeal cancers. In addition, we performed studies to identify HPV integration sites and the relationship of integration to viral-host fusion transcripts and whether integration is required for HPV-associated oncogenesis. Viral integration of HPV into the host genome is not required for the viral life cycle and might not be necessary for cellular transformation, yet HPV integration is frequently reported in cervical and head and neck cancer specimens...
December 1, 2017: Journal of Dental Research
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