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https://www.readbyqxmd.com/read/29777955/perspectives-and-limitations-for-nucleo-t-side-analogs-in-future-hbv-therapies
#1
REVIEW
Massimo Levrero, Miroslava Subic, Francois Villeret, Fabien Zoulim
The latest generation of nucleo(t)side analogs (NAs) provide robust virus suppression with high barrier to resistance. Long term NAs treatment is associated with a partial restoration in HBV-specific T-cell functions, regression of fibrosis, no disease progression and a reduction of HCC risk but rarely lead to cure and life-long treatments is often required. New insights into the hepatitis B viral life cycle and the host immune response have expanded the potential targets for drug therapies with interesting antiviral candidates and novel immunotherapeutic approaches in early stage development...
May 16, 2018: Current Opinion in Virology
https://www.readbyqxmd.com/read/29777911/deficiency-in-gnrh-receptor-trafficking-due-to-a-novel-homozygous-mutation-causes-idiopathic-hypogonadotropic-hypogonadism-in-three-prepubertal-siblings
#2
Rui Zhang, Siyuan Linpeng, Zhuo Li, Yingxi Cao, Hu Tan, Desheng Liang, Lingqian Wu
Idiopathic hypogonadotropic hypogonadism (IHH) is characterized by low levels of gonadotropins and delayed or absent sexual development. Most of the patients are diagnosed in late adolescence or early adulthood. Determining the diagnosis of IHH in prepubertal patients can be challenging. Making a timely, correct diagnosis has important clinical implications. Here we aimed to identify the genetic cause of IHH in three prepubertal siblings from a Chinese Han family and give appropriate treatment advice. Using whole exome sequencing (WES), we identified a novel homozygous GNRHR mutation (NM_000406; c...
May 16, 2018: Gene
https://www.readbyqxmd.com/read/29777794/regulatory-t-cell-targeted-hybrid-nanoparticles-combined-with-immuno-checkpoint-blockage-for-cancer-immunotherapy
#3
Wenquan Ou, Raj Kumar Thapa, Liyuan Jiang, Soe Zar Chi, Milan Gautam, Jae-Hoon Chang, Jee-Heon Jeong, Sae Kwang Ku, Han-Gon Choi, Chul Soon Yong, Jong Oh Kim
Immunosuppression in tumor microenvironments induced by regulatory T (Treg) cells is regarded a critical mechanism of tumor immune escape and poses a major impediment to cancer immunotherapy. In this study, we developed tLyp1 peptide-conjugated hybrid nanoparticles for targeting Treg cells in the tumor microenvironment. The tLyp1 peptide-modified hybrid nanoparticles presented good stability and effective targeting to Treg cells, and they enhanced the effect of imatinib in downregulating Treg cell suppression through inhibition of STAT3 and STAT5 phosphorylation...
May 16, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29777742/a-functional-glycoproteomics-approach-identifies-cd13-as-a-novel-e-selectin-ligand-in-breast-cancer
#4
M A Carrascal, M Silva, J A Ferreira, R Azevedo, D Ferreira, A M N Silva, D Ligeiro, L L Santos, R Sackstein, P A Videira
BACKGROUND: The glycan moieties sialyl-Lewis-X and/or -A (sLeX/A ) are the primary ligands for E-selectin, regulating subsequent tumor cell extravasation into distant organs. However, the nature of the glycoprotein scaffolds displaying these glycans in breast cancer remains unclear and constitutes the focus of the present investigation. METHODS: We isolated glycoproteins that bind E-selectin from the CF1_T breast cancer cell line, derived from a patient with ductal carcinoma...
May 16, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29777261/mitochondrial-quality-control-in-amd-does-mitophagy-play-a-pivotal-role
#5
REVIEW
Juha M T Hyttinen, Johanna Viiri, Kai Kaarniranta, Janusz Błasiak
Age-related macular degeneration (AMD) is the predominant cause of visual loss in old people in the developed world, whose incidence is increasing. This disease is caused by the decrease in macular function, due to the degeneration of retinal pigment epithelium (RPE) cells. The aged retina is characterised by increased levels of reactive oxygen species (ROS), impaired autophagy, and DNA damage that are linked to AMD pathogenesis. Mitophagy, a mitochondria-specific type of autophagy, is an essential part of mitochondrial quality control, the collective mechanism responsible for this organelle's homeostasis...
May 18, 2018: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29777228/effects-of-clomiphene-citrate-on-male-obesity-associated-hypogonadism-a-randomized-double-blind-placebo-controlled-study
#6
Andressa Heimbecher Soares, Nidia Celeste Horie, Lucas Augusto Piccinin Chiang, Bruno Caramelli, Mariana Gomes Matheus, Alexandre Holthausen Campos, Luciana Cavalheiro Marti, Fernanda Agostini Rocha, Marcio C Mancini, Elaine Maria Frade Costa, Cintia Cercato
BACKGROUND: Obesity causes secondary hypogonadism (HG) in men. Standard testosterone (T) replacement therapy improves metabolic parameters but leads to infertility. OBJECTIVE: To evaluate clomiphene citrate (CC) treatment of adult men with male obesity-associated secondary hypogonadism (MOSH). DESIGN: Single-center, randomized, double-blind, placebo-controlled trial. PARTICIPANTS: Seventy-eight men aged 36.5 ± 7...
May 17, 2018: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/29777223/card9-s12n-facilitates-the-production-of-il-5-by-alveolar-macrophages-for-the-induction-of-type-2-immune-responses
#7
Xia Xu, Jin-Fu Xu, Guoxing Zheng, Hai-Wen Lu, Jie-Lin Duan, Wei Rui, Jian-Hong Guan, Li-Qing Cheng, Dan-Dan Yang, Ming-Chao Wang, Quan-Zhen Lv, Jian-Xiong Li, Xueqiang Zhao, Chun-Xia Chen, Peng Shi, Xin-Ming Jia, Xin Lin
The adaptor CARD9 functions downstream of C-type lectin receptors (CLRs) for the sensing of microbial infection, which leads to responses by the TH 1 and TH 17 subsets of helper T cells. The single-nucleotide polymorphism rs4077515 at CARD9 in the human genome, which results in the substitution S12N (CARD9S12N ), is associated with several autoimmune diseases. However, the function of CARD9S12N has remained unknown. Here we generated CARD9S12N knock-in mice and found that CARD9S12N facilitated the induction of type 2 immune responses after engagement of CLRs...
May 18, 2018: Nature Immunology
https://www.readbyqxmd.com/read/29777221/chemokines-and-integrins-independently-tune-actin-flow-and-substrate-friction-during-intranodal-migration-of-t-cells
#8
Miroslav Hons, Aglaja Kopf, Robert Hauschild, Alexander Leithner, Florian Gaertner, Jun Abe, Jörg Renkawitz, Jens V Stein, Michael Sixt
Although much is known about the physiological framework of T cell motility, and numerous rate-limiting molecules have been identified through loss-of-function approaches, an integrated functional concept of T cell motility is lacking. Here, we used in vivo precision morphometry together with analysis of cytoskeletal dynamics in vitro to deconstruct the basic mechanisms of T cell migration within lymphatic organs. We show that the contributions of the integrin LFA-1 and the chemokine receptor CCR7 are complementary rather than positioned in a linear pathway, as they are during leukocyte extravasation from the blood vasculature...
May 18, 2018: Nature Immunology
https://www.readbyqxmd.com/read/29777219/tissue-resident-memory-t-cells-at-the-center-of-immunity-to-solid-tumors
#9
REVIEW
Derk Amsen, Klaas P J M van Gisbergen, Pleun Hombrink, Rene A W van Lier
Immune responses in tissues are constrained by the physiological properties of the tissue involved. Tissue-resident memory T cells (TRM cells) are a recently discovered lineage of T cells specialized for life and function within tissues. Emerging evidence has shown that TRM cells have a special role in the control of solid tumors. A high frequency of TRM cells in tumors correlates with favorable disease progression in patients with cancer, and studies of mice have shown that TRM cells are necessary for optimal immunological control of solid tumors...
May 18, 2018: Nature Immunology
https://www.readbyqxmd.com/read/29777119/changes-in-t-cell-effector-functions-over-an-8-year-period-with-tnf-antagonists-in-patients-with-chronic-inflammatory-rheumatic-diseases
#10
Ilaria Sauzullo, Rossana Scrivo, Paola Sessa, Fabio Mengoni, Vincenzo Vullo, Guido Valesini, Claudio Maria Mastroianni
The aim of the study was to clarify the effect of long-term anti-TNF therapy on T cell function in patients with rheumatologic immune-mediated inflammatory diseases (IMID). The production of IFNγ by T cells was evaluated at baseline and after 1, 2, 4, and 8 years of anti-TNF agents by means of a QuantiFERON-TB Gold In-Tube assay. The T cell proliferation and surface co-expression of CD25/CD134 in response to phytohaemagglutinin together with the in vitro impact of anti-TNF therapy on the functional capacity of T cells were evaluated after 8 years from the onset of the biological treatment...
May 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29777029/cd4-t-cell-affinity-diversity-is-equally-maintained-during-acute-and-chronic-infection
#11
Rakieb Andargachew, Ryan J Martinez, Elizabeth M Kolawole, Brian D Evavold
TCR affinity for peptide MHC dictates the functional efficiency of T cells and their propensity to differentiate into effectors and form memory. However, in the context of chronic infections, it is unclear what the overall profile of TCR affinity for Ag is and if it differs from acute infections. Using the comprehensive affinity analysis provided by the two-dimensional micropipette adhesion frequency assay and the common indirect affinity evaluation methods of MHC class II tetramer and functional avidity, we tracked IAb GP61-80 -specific cells in the mouse model of acute (Armstrong) and chronic (clone 13) lymphocytic choriomeningitis virus infection...
May 18, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29776963/combined-vegf-and-pd-l1-blockade-displays-synergistic-treatment-effects-in-an-autochthonous-mouse-model-of-small-cell-lung-cancer
#12
Lydia Meder, Philipp Schuldt, Martin Thelen, Anna Schmitt, Felix Dietlein, Sebastian Klein, Sven Borchmann, Kerstin Wennhold, Ignacija Vlasic, Sebastian Oberbeck, Richard Riedel, Alexandra Florin, Kristina Golfmann, Hans Anton Schlößer, Margarete Odenthal, Reinhard Büttner, Juergen Wolf, Michael Hallek, Marco Herling, Michael von Bergwelt-Baildon, Hans Christian Reinhardt, Roland T Ullrich
Small cell lung cancer (SCLC) represents the most aggressive pulmonary neoplasm and is often diagnosed at late stage with limited survival, despite combined chemotherapies. We show in an autochthonous mouse model of SCLC that combined anti-VEGF/anti-PD-L1 targeted therapy synergistically improves treatment outcome compared to anti-PD-L1 and anti-VEGF monotherapy. Mice treated with anti-PD-L1 alone relapsed after 3 weeks and were associated with a tumor-associated PD-1/TIM-3 double positive exhausted T cell phenotype...
May 18, 2018: Cancer Research
https://www.readbyqxmd.com/read/29776755/neutral-ph-and-low-glucose-degradation-product-dialysis-fluids-induce-major-early-alterations-of-the-peritoneal-membrane-in-children-on-peritoneal-dialysis
#13
Betti Schaefer, Maria Bartosova, Stephan Macher-Goeppinger, Peter Sallay, Peter Vörös, Bruno Ranchin, Karel Vondrak, Gema Ariceta, Ariane Zaloszyc, Aysun K Bayazit, Uwe Querfeld, Rimante Cerkauskiene, Sara Testa, Christina Taylan, Johan VandeWalle, YokChin Yap, Rafael T Krmar, Rainer Büscher, Anne K Mühlig, Dorota Drozdz, Salim Caliskan, Felix Lasitschka, Sahar Fathallah-Shaykh, Enrico Verrina, Günter Klaus, Klaus Arbeiter, Raj Bhayadia, Anette Melk, Philipp Romero, Bradley A Warady, Franz Schaefer, Akos Ujszaszi, Claus Peter Schmitt
The effect of peritoneal dialysates with low-glucose degradation products on peritoneal membrane morphology is largely unknown, with functional relevancy predominantly derived from experimental studies. To investigate this, we performed automated quantitative histomorphometry and molecular analyses on 256 standardized peritoneal and 172 omental specimens from 56 children with normal renal function, 90 children with end-stage kidney disease at time of catheter insertion, and 82 children undergoing peritoneal dialysis using dialysates with low-glucose degradation products...
May 15, 2018: Kidney International
https://www.readbyqxmd.com/read/29776451/myeloid-specific-tak1-deletion-results-in-reduced-brain-monocyte-infiltration-and-improved-outcomes-after-stroke
#14
Anjali Chauhan, Jacob Hudobenko, Abdullah Al Mamun, Edward C Koellhoffer, Anthony Patrizz, Rodney M Ritzel, Bhanu P Ganesh, Louise D McCullough
BACKGROUND: Activation of transforming growth factor-β-activated kinase 1 (TAK1) occurs after stroke and leads to an exacerbation of brain injury. TAK1 is involved in innate and adaptive immune responses, but it has divergent inflammatory effects that are dependent on the cell type in which it is activated. There is a robust infiltration of myeloid cells after stroke; however, the contribution of myeloid TAK1 to cerebral ischemia is currently unknown. We hypothesized that myeloid-specific deletion of TAK1 would protect against ischemic brain injury...
May 17, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29776424/impaired-cd8-t-cell-antiviral-immunity-following-acute-spinal-cord-injury
#15
Diana M Norden, John R Bethea, Jiu Jiang
BACKGROUND: Spinal cord injury (SCI) disrupts essential neuroimmune communication, leading to severe immune depression. Previous studies confirmed immune dysfunction in mice with chronic SCI and following high thoracic level injury where sympathetic innervation of the spleen is disrupted. Here, we induced a mid-thoracic injury where integrity of the sympathetic response is maintained and investigated the antiviral T cell response to influenza virus after acute SCI. METHODS: One week following a contusion SCI at thoracic level T9, mice were infected intranasally with influenza virus...
May 17, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29776342/dna-methylation-signatures-of-breast-cancer-in-peripheral-t-cells
#16
Surabhi Parashar, David Cheishvili, Niaz Mahmood, Ani Arakelian, Imrana Tanvir, Haseeb Ahmed Khan, Richard Kremer, Catalin Mihalcioiu, Moshe Szyf, Shafaat A Rabbani
BACKGROUND: Immune surveillance acts as a defense mechanism in cancer, and its disruption is involved in cancer progression. DNA methylation reflects the phenotypic identity of cells and recent data suggested that DNA methylation profiles of T cells and peripheral blood mononuclear cells (PBMC) are altered in cancer progression. METHODS: We enrolled 19 females with stage 1 and 2, nine with stage 3 and 4 and 9 age matched healthy women. T cells were isolated from peripheral blood and extracted DNA was subjected to Illumina 450 K DNA methylation array analysis...
May 18, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29776088/how-nonuniform-contact-profiles-of-t-cell-receptors-modulate-thymic-selection-outcomes
#17
Hanrong Chen, Arup K Chakraborty, Mehran Kardar
T cell receptors (TCRs) bind foreign or self-peptides attached to major histocompatibility complex (MHC) molecules, and the strength of this interaction determines T cell activation. Optimizing the ability of T cells to recognize a diversity of foreign peptides yet be tolerant of self-peptides is crucial for the adaptive immune system to properly function. This is achieved by selection of T cells in the thymus, where immature T cells expressing unique, stochastically generated TCRs interact with a large number of self-peptide-MHC; if a TCR does not bind strongly enough to any self-peptide-MHC, or too strongly with at least one self-peptide-MHC, the T cell dies...
March 2018: Physical Review. E
https://www.readbyqxmd.com/read/29775473/na-k-atpase-signaling-mediates-mir-29b-3p-regulation-and-cardiac-fibrosis-formation-in-mice-with-chronic-kidney-disease
#18
Christopher A Drummond, Xiaoming Fan, Steven T Haller, David J Kennedy, Jiang Liu, Jiang Tian
The Na/K-ATPase is an important membrane ion transporter and a signaling receptor that is essential for maintaining normal cell function. The current study examined the role of Na/K-ATPase signaling in regulating miR-29b-3p, an anti-fibrotic microRNA, in a mouse chronic kidney disease (CKD) model (5/6th partial nephrectomy or PNx). The results showed that CKD induced significant reduction of miR-29b-3p expression in the heart tissue by activation of Src and NFκB signaling in these animals. To demonstrate the role of Na/K-ATPase signaling, we also performed the PNx surgery on Na/K-ATPase α1 heterozygous (α1+/-) mice, which expresses ~40% less Na/K-ATPase α1 compared to their wild type littermates (WT) and exhibits deficiency in Na/K-ATPase signaling...
2018: PloS One
https://www.readbyqxmd.com/read/29775441/-the-biological-function-and-significance-of-il-35-in-the-pathogenesis-of-atherosclerosis
#19
EDITORIAL
Mateusz Staciwa, Marlena Broncel
The imbalance of anti-inflammatory /pro- inflammatory cytokines plays an important role in the progression of atherosclerosis. Interleukin 35 (IL-35) is a novel member of the IL-12 family, consisting of an EBVinduced gene 3 (EBI3) subunit and a P35 subunit. IL-35 is an immunesuppressive cytokine mainly produced by regulatory T cells. Accumulating evidence suggests that IL-35 may represent a target for antiatherosclerotic therapy based on its several anti-inflammatory features. This review provide a brief overview of IL-35 biology and the role of IL-35 in the atherosclerosis, autoimmune disease and cancers...
April 23, 2018: Polski Merkuriusz Lekarski: Organ Polskiego Towarzystwa Lekarskiego
https://www.readbyqxmd.com/read/29775417/targeting-histone-methyltransferase-enhancer-of-zeste-homolog-2-inhibits-renal-epithelial-mesenchymal-transition-and-attenuates-renal-fibrosis
#20
Xiaoxu Zhou, Chongxiang Xiong, Evelyn Tolbert, Ting C Zhao, George Bayliss, Shougang Zhuang
Enhancer of zeste homolog-2 (EZH2) is a methyltransferase that induces histone H3 lysine 27 trimethylation (H3K27me3) and functions as an oncogenic factor in many cancer types. Its role in renal epithelial-mesenchymal transition (EMT) remains unknown. In this study, we found that EZH2 and H3K27me3 were highly expressed in mouse kidney with unilateral ureteral obstruction and cultured mouse kidney proximal tubular (TKPT) cells undergoing EMT. Inhibition of EZH2 with 3-deazaneplanocin A (3-DZNeP) attenuated renal fibrosis, which was associated with preserving E-cadherin expression and inhibiting Vimentin up-regulation in the obstructed kidney...
May 18, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
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