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https://www.readbyqxmd.com/read/28535598/antarctic-seals-molecular-biomarkers-as-indicators-for-pollutant-exposure-health-effects-and-diet
#1
K Lehnert, L Weirup, K C Harding, T Härkönen, O Karlsson, J Teilmann
Weddell (Leptonychotes weddellii), Ross (Ommatophoca rossii) and crabeater seals (Lobodon carcinophaga) are phocid seals with a circumpolar distribution around Antarctica. As long-lived and large top predators, they bioaccumulate contaminants and are considered as sentinels of ecosystem health. Antarctic seals are increasingly exposed to climate change, pollution, shipping and fisheries. To reveal and understand possible anthropogenic impacts on their immune and health status, this study investigates sensitive biomarkers of the xenobiotic metabolism and immune system in relation to mercury (Hg) burden...
May 19, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/28535458/mtor-signaling-in-the-differentiation-and-function-of-regulatory-and-effector-t-cells
#2
REVIEW
Hu Zeng, Hongbo Chi
The mechanistic target of rapamycin (mTOR) signaling pathway integrates environmental signals and cellular metabolism to regulate T cell development, activation and differentiation. Recent studies reveal the importance of exquisite control of mTOR activity for proper T cell function, and detailed molecular mechanisms that regulate mTOR signaling in different T cell subsets. Here, we review the latest advances in our understanding of the mTOR pathway and its regulation in the differentiation and function of regulatory T cells and effector T cells...
May 20, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28535250/evidence-for-the-deregulation-of-protein-turnover-pathways-in-atm-deficient-mouse-cerebellum-an-organotypic-study
#3
Catherine D Kim, Ryan E Reed, Meredith A Juncker, Zhide Fang, Shyamal D Desai
Interferon-stimulated gene 15 (ISG15), an antagonist of the ubiquitin pathway, is elevated in cells and brain tissues obtained from ataxia telangiectasia (A-T) patients. Previous studies reveal that an elevated ISG15 pathway inhibits ubiquitin-dependent protein degradation, leading to activation of basal autophagy as a compensatory mechanism for protein turnover in A-T cells. Also, genotoxic stress (ultraviolet [UV] radiation) deregulates autophagy and induces aberrant degradation of ubiquitylated proteins in A-T cells...
May 23, 2017: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/28535205/a-transcriptional-serenaid-the-role-of-noncoding-rnas-in-class-switch-recombination
#4
William T Yewdell, Jayanta Chaudhuri
During an immune response, activated B cells may undergo class switch recombination (CSR), a molecular rearrangement that allows B cells to switch from expressing IgM and IgD to a secondary antibody heavy chain isotype such as IgG, IgA, or IgE. Secondary antibody isotypes provide the adaptive immune system with distinct effector functions to optimally combat various pathogens. CSR occurs between repetitive DNA elements within the immunoglobulin heavy chain (Igh) locus, termed switch (S) regions, and requires the DNA modifying enzyme activation-induced cytidine deaminase (AID)...
May 23, 2017: International Immunology
https://www.readbyqxmd.com/read/28535201/regulatory-t-cells-ameliorate-tissue-plasminogen-activator-induced-brain-haemorrhage-after-stroke
#5
Leilei Mao, Peiying Li, Wen Zhu, Wei Cai, Zongjian Liu, Yanling Wang, Wenli Luo, Ruth A Stetler, Rehana K Leak, Weifeng Yu, Yanqin Gao, Jun Chen, Gang Chen, Xiaoming Hu
Delayed thrombolytic treatment with recombinant tissue plasminogen activator (tPA) may exacerbate blood-brain barrier breakdown after ischaemic stroke and lead to lethal haemorrhagic transformation. The immune system is a dynamic modulator of stroke response, and excessive immune cell accumulation in the cerebral vasculature is associated with compromised integrity of the blood-brain barrier. We previously reported that regulatory T cells, which function to suppress excessive immune responses, ameliorated blood-brain barrier damage after cerebral ischaemia...
May 22, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28535087/cytotoxic-t-cells-in-chronic-idiopathic-neutropenia-express-restricted-antigen-receptors
#6
Semeli Mastrodemou, Evangelia Stalika, Anna Vardi, Katerina Gemenetzi, Michalis Spanoudakis, Maria Karypidou, Irene Mavroudi, Anastasia Hadzidimitriou, Catherine Stavropoulos-Giokas, Helen A Papadaki, Kostas Stamatopoulos
Chronic idiopathic neutropenia (CIN) is an acquired disorder of granulopoiesis characterized by female predominance and mostly uncomplicated course. Crucial to CIN pathophysiology is the presence of activated T lymphocytes with myelosuppressive properties in both peripheral blood (PB) and bone marrow (BM). We systematically profiled the T cell receptor beta chain (TRB) gene repertoire in CD8(+) cells of 34 CIN patients through subcloning/Sanger sequencing analysis of TRBV-TRBD-TRBJ gene rearrangements. Remarkable repertoire skewing and oligoclonality were observed, along with shared clonotypes between different patients, alluding to antigen selection...
May 23, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28534937/the-inhibitory-effect-of-meg3-mir-214-aifm2-axis-on-the-growth-of-t-cell-lymphoblastic-lymphoma
#7
Fang-Yi Fan, Rui Deng, Hai Yi, Hao-Ping Sun, Yan Zeng, Guang-Cui He, Yi Su
T-cell lymphoblastic lymphoma (T-LBL) is an aggressive malignancy with poor prognosis and high recurrence rate. Long non-coding RNA (lncRNA)-MEG3 is an important tumor suppressor in various cancers. The present study investigated the potential role of maternally expressed gene 3 (MEG3) in the progression of T-LBL. Suppressed expression of MEG3 was detected in T-LBL tissues compared with adjacent histologically normal tissues. Down-regulated level of MEG3 was also found in three T-LBL cell lines (CCRF-CEM, Jurkat and SUP-T1) compared with human T-cell line H9...
May 17, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28534814/autophagy-regulates-proteasome-inhibitor-induced-pigmentation-in-human-embryonic-stem-cell-derived-retinal-pigment-epithelial-cells
#8
Kati Juuti-Uusitalo, Ali Koskela, Niko Kivinen, Johanna Viiri, Juha M T Hyttinen, Mika Reinisalo, Arto Koistinen, Hannu Uusitalo, Debasish Sinha, Heli Skottman, Kai Kaarniranta
The impairment of autophagic and proteasomal cleansing together with changes in pigmentation has been documented in retinal pigment epithelial (RPE) cell degeneration. However, the function and co-operation of these mechanisms in melanosome-containing RPE cells is still unclear. We show that inhibition of proteasomal degradation with MG-132 or autophagy with bafilomycin A1 increased the accumulation of premelanosomes and autophagic structures in human embryonic stem cell (hESC)-derived RPE cells. Consequently, upregulation of the autophagy marker p62 (also known as sequestosome-1, SQSTM1) was confirmed in Western blot and perinuclear staining...
May 19, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28534531/unravelling-the-biology-of-sclc-implications-for-therapy
#9
REVIEW
Joshua K Sabari, Benjamin H Lok, James H Laird, John T Poirier, Charles M Rudin
Small-cell lung cancer (SCLC) is an aggressive malignancy associated with a poor prognosis. First-line treatment has remained unchanged for decades, and a paucity of effective treatment options exists for recurrent disease. Nonetheless, advances in our understanding of SCLC biology have led to the development of novel experimental therapies. Poly [ADP-ribose] polymerase (PARP) inhibitors have shown promise in preclinical models, and are under clinical investigation in combination with cytotoxic therapies and inhibitors of cell-cycle checkpoints...
May 23, 2017: Nature Reviews. Clinical Oncology
https://www.readbyqxmd.com/read/28534513/protein-disulfide-isomerase-a4-acts-as-a-novel-regulator-of-cancer-growth-through-the-procaspase-pathway
#10
T-F Kuo, T-Y Chen, S-T Jiang, K-W Chen, Y-M Chiang, Y-J Hsu, Y-J Liu, H-M Chen, K K Yokoyama, K-C Tsai, H-H Yeh, Y-R Chen, M-T Yang, C-Y Yang, W-C Yang
Protein disulfide isomerase a4 (PDIA4) is implicated in the growth and death of tumor cells; however, its molecular mechanism and therapeutic potential in cancer are unclear. Here, we found that PDIA4 expression was upregulated in a variety of tumor cell lines and human lung adenocarcinoma tissues. Knockdown and overexpression of PDIA4 in tumor cells showed that PDIA4 facilitated cell growth via the reduction of caspases 3 and 7 activity. Consistently, Lewis lung carcinoma cells overexpressing PDIA4 grew faster than did parental cells in tumor-bearing mice, as shown by a reduced survival rate, increased tumor size and metastasis, and decreased cell death and caspases 3 and 7 activity...
May 22, 2017: Oncogene
https://www.readbyqxmd.com/read/28534509/a-novel-interaction-of-pak4-with-ppar%C3%AE-to-regulate-nox1-and-radiation-induced-epithelial-to-mesenchymal-transition-in-glioma
#11
D Kesanakurti, D Maddirela, Y K Banasavadi-Siddegowda, T-H Lai, Z Qamri, N K Jacob, D Sampath, S Mohanam, B Kaur, V K Puduvalli
Tumor recurrence in glioblastoma (GBM) is, in part, attributed to increased epithelial-to-mesenchymal transition (EMT) and enhanced tumor cell dissemination in adjacent brain parenchyma after ionizing radiation (IR). EMT is associated with aggressive behavior, increased stem-like characteristics and treatment resistance in malignancies; however, the underlying signaling mechanisms that regulate EMT are poorly understood. We identified grade-dependent p21-activated kinases 4 (PAK4) upregulation in gliomas and further determined its role in mesenchymal transition and radioresistance...
May 22, 2017: Oncogene
https://www.readbyqxmd.com/read/28534443/cd59-polymorphisms-are-associated-with-gene-expression-and-different-sexual-susceptibility-to-pemphigus-foliaceus
#12
Amanda Salviano-Silva, Maria Luiza Petzl-Erler, Angelica Beate Winter Boldt
Pemphigus foliaceus (PF) is an autoimmune disease, endemic in Brazilian rural areas, characterized by acantholysis and accompanied by complement activation, with generalized or localized distribution of painful epidermal blisters. CD59 is an essential complement regulator, inhibiting formation of the membrane attack complex, and mediating signal transduction and activation of T lymphocytes. CD59 has different transcripts by alternative splicing, of which only two are widely expressed, suggesting the presence of regulatory sites in their noncoding regions...
May 23, 2017: Autoimmunity
https://www.readbyqxmd.com/read/28534426/the-immunological-personality-of-close-relatives-of-sle-patients
#13
M R Salaman, D A Isenberg
Immunological abnormalities seen in relatives of patients with autoimmune disorders can be useful in understanding the pathogenesis of the disease since, unlike in patients, they cannot result from the disease process or drug treatment. In this article we present a brief overview of our studies of the basic immunological status of close relatives of SLE patients. We looked at blood levels of IgG, IgM and antibodies to double-stranded DNA, as well as at NK cell numbers and cytotoxic activity and the levels of NKT, B and T cells...
January 1, 2017: Lupus
https://www.readbyqxmd.com/read/28534412/exploration-of-biogenic-nano-chemobiotics-fabricated-by-sliver-nanoparticle-and-galactoxyloglucan-with-an-efficient-bio-distribution-in-solid-tumor-investigated-by-sers-fingerprinting
#14
Manu M Joseph, Jyothi B Nair, Ramya N Adukkadan, Neethu Hari, Raveendran Pillai, Ananthakrishnan J Nair, Kaustabh Kumar Maiti, Sreelekha Therakathinal T
An incredible exploration of a dual modality nano composite wherein, chemotherapy in fusion with antibacterial efficacy obtained in a biogenic fabrication, which transformed as a novel nano-chemobiotics (NCB) prevailing fundamental molecular level investigation by surface enhanced Raman scattering (SERS) platform. The nano composite is a facile, robust and eco-friendly constitution between silver nanoparticles (SNPs) and a naturally occurring galactoxyloglucan (PST001) denoted as SNP@PST which displayed biocompatibility with an upgraded selective cytotoxicity towards cancer cells...
May 23, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28534337/-mir-145-inhibits-drug-resistance-to-oxaliplatin-in-colorectal-cancer-cells-through-regulating-g-protein-coupled-receptor-98
#15
Qiang Fu, Jing Cheng, Jindai Zhang, Yonglei Zhang, Xiaobing Chen, Jianguo Xie, Suxia Luo
OBJECTIVE: To predict and identify the target gene of miR-145, and to explore the underlying mechanism of the inhibition of miR-145 on drug resistance to Oxaliplatin (L-OHP) in human colorectal cancer cells. METHODS: L-OHP-resistant human colorectal cancer cell line (HCT116/L-OHP) was established in vitro by exposing to increased concentrations of L-OHP in cell culture medium. MiR-145-mimics and its negative control (NC-miRNA) were transfected into HCT116/L-OHP cells using liposome to establish HCT116/L-OHP(mimics) over-expressing miR-145 and HCT116/L-OHP(NC)...
May 25, 2017: Zhonghua Wei Chang Wai Ke za Zhi, Chinese Journal of Gastrointestinal Surgery
https://www.readbyqxmd.com/read/28534310/combination-immunotherapy-for-type-1-diabetes
#16
REVIEW
Robert N Bone, Carmella Evans-Molina
PURPOSE OF REVIEW: Type 1 diabetes (T1D) is an autoimmune disease marked by β-cell destruction. Immunotherapies for T1D have been investigated since the 1980s and have focused on restoration of tolerance, T cell or B cell inhibition, regulatory T cell (Treg) induction, suppression of innate immunity and inflammation, immune system reset, and islet transplantation. The purpose of this review is to provide an overview and lessons learned from single immunotherapy trials, describe recent and ongoing combination immunotherapy trials, and provide perspectives on strategies for future combination clinical interventions aimed at preserving insulin secretion in T1D...
July 2017: Current Diabetes Reports
https://www.readbyqxmd.com/read/28534291/ultra-sensitive-measurement-of-il-17a-and-il-17f-in-psoriasis-patient-serum-and-skin
#17
Catherine Soderstrom, Gabriel Berstein, Weidong Zhang, Hernan Valdez, Lori Fitz, Max Kuhn, Stephanie Fraser
Interleukin 17 is a family of cytokines that play a central role in many autoimmune and inflammatory diseases. IL-17A has been implicated as a key driver of psoriasis, mediating a chronic cycle of T-cell activation, keratinocyte proliferation and angiogenesis. It has been hypothesized that expression of IL-17A and the related cytokine IL-17F could be used as predictive biomarkers for therapeutic response, though they have been difficult to measure locally or in circulation because of their low abundance. We developed ultrasensitive methods for measuring IL-17A and IL-17F in human serum samples and found that serum from psoriasis patients had higher and a broader range of concentrations of both IL-17 proteins compared to healthy volunteers...
May 22, 2017: AAPS Journal
https://www.readbyqxmd.com/read/28534262/inflammatory-changes-in-paravertebral-sympathetic-ganglia-in-two-rat-pain-models
#18
Ai-Ling Li, Jing-Dong Zhang, Wenrui Xie, Judith A Strong, Jun-Ming Zhang
Injury to peripheral nerves can lead to neuropathic pain, along with well-studied effects on sensory neurons, including hyperexcitability, abnormal spontaneous activity, and neuroinflammation in the sensory ganglia. Neuropathic pain can be enhanced by sympathetic activity. Peripheral nerve injury may also damage sympathetic axons or expose them to an inflammatory environment. In this study, we examined the lumbar sympathetic ganglion responses to two rat pain models: ligation of the L5 spinal nerve, and local inflammation of the L5 dorsal root ganglion (DRG), which does not involve axotomy...
May 22, 2017: Neuroscience Bulletin
https://www.readbyqxmd.com/read/28534191/tgf-%C3%AE-in-inflammatory-bowel-disease-a-key-regulator-of-immune-cells-epithelium-and-the-intestinal-microbiota
#19
REVIEW
Sozaburo Ihara, Yoshihiro Hirata, Kazuhiko Koike
Inflammatory bowel disease (IBD) is defined as chronic intestinal inflammation, and includes ulcerative colitis and Crohn's disease. Multiple factors are involved in the pathogenesis of IBD, and the condition is characterized by aberrant mucosal immune reactions to intestinal microbes in genetically susceptible hosts. Transforming growth factor-β (TGF-β) is an immune-suppressive cytokine produced by many cell types and activated by integrins. Active TGF-β binds to its receptor and regulates mucosal immune reactions through the TGF-β signaling pathway...
May 22, 2017: Journal of Gastroenterology
https://www.readbyqxmd.com/read/28534088/the-ppar-gamma-binding-sequence-pal3-is-necessary-for-basal-but-dispensable-for-high-fat-diet-regulated-human-renin-expression-in-the-kidney
#20
Peter Lachmann, Jenny Selbmann, Linda Hickmann, Bernd Hohenstein, Christian Hugo, Vladimir T Todorov
We reported earlier that PPAR-gamma regulates renin transcription through a human-specific atypical binding sequence termed hRen-Pal3. Here we developed a mouse model to investigate the functional relevance of the hRen-Pal3 sequence in vivo since it might be responsible for the increased renin production in obesity and thus for the development of accompanying arterial hypertension. We used bacterial artificial chromosome construct and co-placement strategy to generate two transgenic mouse lines expressing the human renin gene from identical genomic locus without affecting the intrinsic mouse renin expression...
May 22, 2017: Pflügers Archiv: European Journal of Physiology
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