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https://www.readbyqxmd.com/read/29786876/temporal-and-long-term-gut-microbiota-variation-in-allergic-disease-a-prospective-study-from-infancy-to-school-age
#1
Kotryna Simonyté Sjödin, Marie-Louise Hammarström, Patrik Rydén, Andreas Sjödin, Olle Hernell, Lars Engstrand, Christina E West
BACKGROUND: Compositional changes of the early life gut microbiota have been implicated in IgE-associated allergic disease but there is lack of longitudinal studies. We examined gut microbiota development from infancy to school age in relation to onset of IgE-associated allergic diseases. At 8 years of age, we also examined the relationship between gut microbiota and T-cell regulation, estimated as responses to polyclonal T-cell activation. METHODS: Stool samples were collected from 93 children at 4, 6 and 13 months, and 8 years of age...
May 22, 2018: Allergy
https://www.readbyqxmd.com/read/29786078/targeting-the-upstream-transcriptional-activator-of-pd-l1-as-an-alternative-strategy-in-melanoma-therapy
#2
Bo Zhu, Liming Tang, Shuyang Chen, Chengqian Yin, Shiguang Peng, Xin Li, Tongzheng Liu, Wei Liu, Changpeng Han, Lukasz Stawski, Zhi-Xiang Xu, Guangbiao Zhou, Xiang Chen, Xiumei Gao, Colin R Goding, Nan Xu, Rutao Cui, Peng Cao
Programmed cell death ligand 1 (PD-L1) interacts with programmed cell death protein-1 (PD-1) as an immune checkpoint. Reactivating the immune response by inhibiting PD-L1 using therapeutic antibodies provides substantial clinical benefits in many, though not all, melanoma patients. However, transcriptional suppression of PD-L1 expression as an alternative therapeutic anti-melanoma strategy has not been exploited. Here we provide biochemical evidence demonstrating that ultraviolet radiation (UVR) induction of PD-L1 in skin is directly controlled by nuclear factor E2-related transcription factor 2 (NRF2)...
May 22, 2018: Oncogene
https://www.readbyqxmd.com/read/29786075/tp53-gain-of-function-mutation-promotes-inflammation-in-glioblastoma
#3
Seok Won Ham, Hee-Young Jeon, Xiong Jin, Eun-Jung Kim, Jun-Kyum Kim, Yong Jae Shin, Yeri Lee, Se Hoon Kim, Seon Yong Lee, Sunyoung Seo, Min Gi Park, Hye-Mi Kim, Do-Hyun Nam, Hyunggee Kim
Glioblastoma (GBM), the most severe and common brain tumor in adults, is characterized by multiple somatic mutations and aberrant activation of inflammatory responses. Immune cell infiltration and subsequent inflammation cause tumor growth and resistance to therapy. Somatic loss-of-function mutations in the gene encoding tumor suppressor protein p53 (TP53) are frequently observed in various cancers. However, numerous studies suggest that TP53 regulates malignant phenotypes by gain-of-function (GOF) mutations...
May 21, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29786074/constitutive-interferon-signaling-maintains-critical-threshold-of-mlkl-expression-to-license-necroptosis
#4
Joseph Sarhan, Beiyun C Liu, Hayley I Muendlein, Chi G Weindel, Irina Smirnova, Amy Y Tang, Vladimir Ilyukha, Maxim Sorokin, Anton Buzdin, Katherine A Fitzgerald, Alexander Poltorak
Interferons (IFNs) are critical determinants in immune-competence and autoimmunity, and are endogenously regulated by a low-level constitutive feedback loop. However, little is known about the functions and origins of constitutive IFN. Recently, lipopolysaccharide (LPS)-induced IFN was implicated as a driver of necroptosis, a necrotic form of cell death downstream of receptor-interacting protein (RIP) kinase activation and executed by mixed lineage kinase like-domain (MLKL) protein. We found that the pre-established IFN status of the cell, instead of LPS-induced IFN, is critical for the early initiation of necroptosis in macrophages...
May 21, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29786070/selective-elimination-of-senescent-cells-by-mitochondrial-targeting-is-regulated-by-ant2
#5
Sona Hubackova, Eliska Davidova, Katerina Rohlenova, Jan Stursa, Lukas Werner, Ladislav Andera, LanFeng Dong, Mikkel G Terp, Zdenek Hodny, Henrik J Ditzel, Jakub Rohlena, Jiri Neuzil
Cellular senescence is a form of cell cycle arrest that limits the proliferative potential of cells, including tumour cells. However, inability of immune cells to subsequently eliminate senescent cells from the organism may lead to tissue damage, inflammation, enhanced carcinogenesis and development of age-related diseases. We found that the anticancer agent mitochondria-targeted tamoxifen (MitoTam), unlike conventional anticancer agents, kills cancer cells without inducing senescence in vitro and in vivo. Surprisingly, it also selectively eliminates both malignant and non-cancerous senescent cells...
May 21, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29785918/proteomic-analysis-of-the-effects-of-lutein-on-mammary-gland-metabolism-in-dairy-cows
#6
Caihong Wang, Chong Wang, Jianxin Liu, Hongyun Liu
The aim of the research reported in this Research Communication was to identify differentially expressed proteins in dairy cows with normal and lutein diet and to elucidate the mechanisms of lutein-induced effects on bovine mammary gland metabolism using a comparative proteomic approach. Thirty-three differentially expressed proteins were identified from mammary gland of control diet-fed and lutein diet-fed dairy cows. Among these proteins, 15 were upregulated and 18 were downregulated in the lutein group. Functional analysis of the differentially expressed proteins showed that increased blood flow, depressed glycolysis, enhanced lactose anabolism, decreased fatty acid oxidation and up-regulated beta lactoglobulin expression were connected with lutein addition...
May 2018: Journal of Dairy Research
https://www.readbyqxmd.com/read/29785197/applying-statistical-and-complex-network-methods-to-explore-the-key-signaling-molecules-of-acupuncture-regulating-neuroendocrine-immune-network
#7
Kuo Zhang, Xin-Meng Guo, Ya-Wen Yan, Yang-Yang Liu, Zhi-Fang Xu, Xue Zhao, Jiang Wang, Yi Guo, Kai Li, Sha-Sha Ding
The mechanisms of acupuncture are still unclear. In order to reveal the regulatory effect of manual acupuncture (MA) on the neuroendocrine-immune (NEI) network and identify the key signaling molecules during MA modulating NEI network, we used a rat complete Freund's adjuvant (CFA) model to observe the analgesic and anti-inflammatory effect of MA, and, what is more, we used statistical and complex network methods to analyze the data about the expression of 55 common signaling molecules of NEI network in ST36 (Zusanli) acupoint, and serum and hind foot pad tissue...
2018: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/29785025/an-immune-beige-adipocyte-communication-via-nicotinic-acetylcholine-receptor-signaling
#8
Heejin Jun, Hui Yu, Jianke Gong, Juan Jiang, Xiaona Qiao, Eric Perkey, Dong-Il Kim, Margo P Emont, Alexander G Zestos, Jung-Sun Cho, Jianfeng Liu, Robert T Kennedy, Ivan Maillard, X Z Shawn Xu, Jun Wu
Beige adipocytes have recently been shown to regulate energy dissipation when activated and help organisms defend against hypothermia and obesity. Prior reports indicate that beige-like adipocytes exist in adult humans and that they may present novel opportunities to curb the global epidemic in obesity and metabolic illnesses. In an effort to identify unique features of activated beige adipocytes, we found that expression of the cholinergic receptor nicotinic alpha 2 subunit (Chrna2) was induced in subcutaneous fat during the activation of these cells and that acetylcholine-producing immune cells within this tissue regulated this signaling pathway via paracrine mechanisms...
May 21, 2018: Nature Medicine
https://www.readbyqxmd.com/read/29784994/designing-natural-and-synthetic-immune-tissues
#9
REVIEW
Emily A Gosselin, Haleigh B Eppler, Jonathan S Bromberg, Christopher M Jewell
Vaccines and immunotherapies have provided enormous improvements for public health, but there are fundamental disconnects between where most studies are performed-in cell culture and animal models-and the ultimate application in humans. Engineering immune tissues and organs, such as bone marrow, thymus, lymph nodes and spleen, could be instrumental in overcoming these hurdles. Fundamentally, designed immune tissues could serve as in vitro tools to more accurately study human immune function and disease, while immune tissues engineered for implantation as next-generation vaccines or immunotherapies could enable direct, on-demand control over generation and regulation of immune function...
May 21, 2018: Nature Materials
https://www.readbyqxmd.com/read/29784908/integration-of-multi-omics-data-and-deep-phenotyping-enables-prediction-of-cytokine-responses
#10
Olivier B Bakker, Raul Aguirre-Gamboa, Serena Sanna, Marije Oosting, Sanne P Smeekens, Martin Jaeger, Maria Zorro, Urmo Võsa, Sebo Withoff, Romana T Netea-Maier, Hans J P M Koenen, Irma Joosten, Ramnik J Xavier, Lude Franke, Leo A B Joosten, Vinod Kumar, Cisca Wijmenga, Mihai G Netea, Yang Li
The immune response to pathogens varies substantially among people. Whereas both genetic and nongenetic factors contribute to interperson variation, their relative contributions and potential predictive power have remained largely unknown. By systematically correlating host factors in 534 healthy volunteers, including baseline immunological parameters and molecular profiles (genome, metabolome and gut microbiome), with cytokine production after stimulation with 20 pathogens, we identified distinct patterns of co-regulation...
May 21, 2018: Nature Immunology
https://www.readbyqxmd.com/read/29784888/identification-of-brain-metastasis-genes-and-therapeutic-evaluation-of-histone-deacetylase-inhibitors-in-a-clinically-relevant-model-of-breast-cancer-brain-metastasis
#11
Soo-Hyun Kim, Richard P Redvers, Lap Hing Chi, Xiawei Ling, Andrew J Lucke, Robert C Reid, David P Fairlie, Ana Carolina Baptista Moreno Martin, Robin L Anderson, Delphine Denoyer, Normand Pouliot
Breast cancer brain metastasis remains largely incurable. While several mouse models have been developed to investigate the genes and mechanisms regulating breast cancer brain metastasis, these models often lack clinical relevance since they require the use of immune-compromised mice and/or are poorly metastatic to brain from the mammary gland. We describe the development and characterisation of an aggressive brain metastatic variant of the 4T1 syngeneic model (4T1Br4) that spontaneously metastasises to multiple organs, but is selectively more metastatic to the brain from the mammary gland than parental 4T1 tumours...
May 21, 2018: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/29784788/mistimed-food-intake-and-sleep-alters-24-hour-time-of-day-patterns-of-the-human-plasma-proteome
#12
Christopher M Depner, Edward L Melanson, Andrew W McHill, Kenneth P Wright
Proteomics holds great promise for understanding human physiology, developing health biomarkers, and precision medicine. However, how much the plasma proteome varies with time of day and is regulated by the master circadian suprachiasmatic nucleus brain clock, assessed here by the melatonin rhythm, is largely unknown. Here, we assessed 24-h time-of-day patterns of human plasma proteins in six healthy men during daytime food intake and nighttime sleep in phase with the endogenous circadian clock (i.e., circadian alignment) versus daytime sleep and nighttime food intake out of phase with the endogenous circadian clock (i...
May 21, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29784765/dawdle-interacts-with-dicer-like-proteins-to-mediate-small-rna-biogenesis
#13
Shuxin Zhang, Yongchao Dou, Shengjun Li, Guodong Ren, David Chevalier, Chi Zhang, Bin Yu
DAWDLE (DDL) is a conserved forkhead-associated (FHA) domain-containing protein with essential roles in plant development and immunity. It acts in the biogenesis of microRNAs (miRNAs) and endogenous small interfering RNAs (siRNAs), which regulate gene expression at the transcriptional and/or post-transcriptional levels. However, the functional mechanism of DDL and its impact on exogenous siRNAs remain elusive. Here we report that DDL is required for the biogenesis of siRNAs derived from sense transgenes and inverted-repeat transgenes...
May 21, 2018: Plant Physiology
https://www.readbyqxmd.com/read/29784761/slc15a2-and-slc15a4-mediate-the-transport-of-bacterially-derived-di-tripeptides-to-enhance-the-nucleotide-binding-oligomerization-domain-dependent-immune-response-in-mouse-bone-marrow-derived-macrophages
#14
Yongjun Hu, Feifeng Song, Huidi Jiang, Gabriel Nuñez, David E Smith
There is increasing evidence that proton-coupled oligopeptide transporters (POTs) can transport bacterially derived chemotactic peptides and therefore reside at the critical interface of innate immune responses and regulation. However, there is substantial contention regarding how these bacterial peptides access the cytosol to exert their effects and which POTs are involved in facilitating this process. Thus, the current study proposed to determine the (sub)cellular expression and functional activity of POTs in macrophages derived from mouse bone marrow and to evaluate the effect of specific POT deletion on the production of inflammatory cytokines in wild-type, Pept2 knockout and Pht1 knockout mice...
May 21, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29784674/clinically-relevant-cytotoxic-immune-cell-signatures-and-clonal-expansion-of-t-cell-receptors-in-high-risk-mycn-not-amplified-human-neuroblastoma
#15
Jun S Wei, Igor B Kuznetsov, Shile Zhang, Young K Song, Shahab Asgharzadeh, Sivasish Sindiri, Xinyu Wen, Rajesh Patidar, Sushma Nagaraj, Ashley Walton, Jaime M Guidry Auvil, Daniela S Gerhard, Aysen Yuksel, Daniel R Catchpoole, Stephen M Hewitt, Paul M Sondel, Robert C Seeger, John M Maris, Javed Khan
PURPOSE: High-risk neuroblastoma is an aggressive disease. DNA sequencing studies have revealed a paucity of actionable genomic alterations and a low mutation burden, posing challenges to develop effective novel therapies. We used RNA sequencing (RNA-seq) to investigate the biology of this disease including a focus on tumor-infiltrating lymphocytes (TILs). EXPERIMENTAL DESIGN: We performed deep RNA-seq on pre-treatment diagnostic tumors from 129 high-risk and 21 low- or intermediate-risk patients with neuroblastomas...
May 21, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29784649/small-molecular-inhibitors-targeting-protein-sumoylation-as-novel-anticancer-compounds
#16
Yanfang Yang, Zijing Xia, Xixi Wang, Xinyu Zhao, Zenghua Sheng, Yang Ye, Gu He, Liangxue Zhou, Hongxia Zhu, Ningzhi Xu, Shufang Liang
SUMOylation, one of post-translational modifications, is covalently modified on lysine residues of a target protein through an enzymatic cascade reaction similar to protein ubiquitination. Along with identification of many SUMOylated proteins, protein SUMOylation has been proven to regulate multiple biological activities including transcription, cell cycle, DNA repair and innate immunity. The dysregulation of protein SUMOylation and deSUMOylation modification is linked with carcinogenesis and tumor progression...
May 21, 2018: Molecular Pharmacology
https://www.readbyqxmd.com/read/29784646/latest-developments-in-muc1-immunotherapy
#17
REVIEW
Joyce Taylor-Papadimitriou, Joy M Burchell, Rosalind Graham, Richard Beatson
Currently, there is renewed interest in attempting to recruit the host immune system to eliminate cancers, and within this renewed activity, MUC1 continues to arouse interest. MUC1 has been considered a possible therapeutic target for the past 30 years as it is up-regulated, aberrantly glycosylated and its polarization is lost in many adenocarcinomas. Moreover, MUC1 is expressed by some haematopoietic cancers, including acute myeloid leukaemia and myeloma. Although multiple clinical trials have been initiated and immune responses have been documented, effective clinical benefit worthy of approval for general application has not as yet been achieved...
May 21, 2018: Biochemical Society Transactions
https://www.readbyqxmd.com/read/29783985/the-doses-of-plasmid-backbone-plays-a-major-role-in-determining-the-hbv-clearance-in-hydrodynamic-injection-mouse-model
#18
Xian Wang, Jianmin Zhu, Yong Zhang, Yue Li, Tai Ma, Qun Li, Jiegou Xu, Long Xu
BACKGROUND: Hepatitis B virus (HBV) chronically infects approximately 350 million people worldwide, causing a major risk of liver disease and hepatocellular carcinoma (HCC). Many mouse models have been tried to establish HBV infection through injection with various HBV-containing plasmids. However, it is not well understood that different plasmids, all of which contain the similar HBV genome, even the same plasmids with different dose, results in opposite immune responses toward HBV. METHODS: In this study, we investigated the role of HBV-containing plasmid backbones and the HBcAg in determining the HBV persistence...
May 21, 2018: Virology Journal
https://www.readbyqxmd.com/read/29783667/bone-marrow-defects-and-platelet-function-a-focus-on-mds-and-cll
#19
REVIEW
Sarah Luu, Elizabeth E Gardiner, Robert K Andrews
The bloodstream typically contains >500 billion anucleate circulating platelets, derived from megakaryocytes in the bone marrow. This review will focus on two interesting aspects of bone marrow dysfunction and how this impacts on the quality of circulating platelets. In this regard, although megakaryocytes are from the myeloid lineage leading to granulocytes (including neutrophils), erythrocytes, and megakaryocytes/platelets, recent evidence has shown that defects in the lymphoid lineage leading to B cells, T cells, and natural killer (NK) cells also result in abnormal circulating platelets...
May 18, 2018: Cancers
https://www.readbyqxmd.com/read/29783162/a-peripheral-immune-response-to-remembering-trauma-contributes-to-the-maintenance-of-fear-memory-in-mice
#20
Matthew B Young, Leonard L Howell, Lauren Hopkins, Cassandra Moshfegh, Zhe Yu, Lauren Clubb, Jessica Seidenberg, Jeanie Park, Adam P Swiercz, Paul J Marvar
Alterations in peripheral immune markers are observed in individuals with post-traumatic stress disorder (PTSD). PTSD is characterized in part by impaired extinction of fear memory for a traumatic experience. We hypothesized that fear memory extinction is regulated by immune signaling stimulated when fear memory is retrieved. The relationship between fear memory and the peripheral immune response was tested using auditory Pavlovian fear conditioning in mice. Memory for the association was quantified by the amount of conditioned freezing exhibited in response to the conditioned stimulus (CS), extinction and time-dependent changes in circulating inflammatory cytokines...
May 17, 2018: Psychoneuroendocrinology
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