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https://www.readbyqxmd.com/read/29156563/wnt-inhibitory-activity-of-malus-pumila-miller-cv-annurca-and-malus-domestica-cv-limoncella-apple-extracts-on-human-colon-rectal-cells-carrying-familial-adenomatous-polyposis-mutations
#1
Gennaro Riccio, Maria Maisto, Sara Bottone, Nadia Badolati, Giovanni Battista Rossi, Gian Carlo Tenore, Mariano Stornaiuolo, Ettore Novellino
Inhibitors of the Wingless-related Integration site (WNT)/β-catenin pathway have recently been under consideration as potential chemopreventive agents against Familial Adenomatous Polyposis (FAP). This autosomal-dominant syndrome is caused by germline mutations in the gene coding for the protein APC and leads to hyperactivation of the WNT/β-catenin signaling pathway, uncontrolled intestinal cell proliferation and formation of adenocarcinomas. The aim of the present work was to: (i) test, on in vitro cultures of cells carrying FAP mutations and on ex vivo biopsies of FAP patients, the WNT inhibitory activity of extracts from two common southern Italian apples, Malus pumila Miller cv...
November 18, 2017: Nutrients
https://www.readbyqxmd.com/read/29155764/multiplex-cytokine-profiling-of-stimulated-mouse-splenocytes-using-a-cytometric-bead-based-immunoassay-platform
#2
Jason S Lehmann, Amy Zhao, Binggang Sun, Weiping Jiang, Shaoquan Ji
Bead-based immunoassays employ the same basic principle as sandwich immunoassays. Capture beads, which can be differentiated by size and internal allophycocyanin (APC) fluorescence intensity, are conjugated to antibodies specific to a particular analyte. Next, a selected panel of defined capture bead sets is incubated with a biological sample containing target analytes specific to the capture antibodies. A biotinylated detection antibody cocktail is added, which leads to the formation of capture bead-analyte-detection antibody sandwiches...
November 9, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29154958/pathogenic-th17-inflammation-is-sustained-in-the-lungs-by-conventional-dendritic-cells-and-tlr4-signaling
#3
Karim H Shalaby, Miranda R Lyons-Cohen, Gregory S Whitehead, Seddon Y Thomas, Immo Prinz, Hideki Nakano, Donald N Cook
BACKGROUND: Mechanisms that elicit mucosal Th17 cell responses have been described, yet how these cells are sustained in chronically inflamed tissues remains unclear. OBJECTIVE: We sought to understand whether the maintenance of lung Th17 inflammation requires environmental agents in addition to antigen, and to identify the lung antigen-presenting cell types (APCs) that sustain the self-renewal of Th17 cells. METHODS: Animals were repeatedly exposed to aspiration of ovalbumin alone, or together with environmental adjuvants, including extracts of common house dust (HDE), to test their role in maintaining lung inflammation...
November 14, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29151835/opuntia-humifusa-modulates-morphological-changes-characteristic-of-asthma-via-il-4-and-il-13-in-an-asthma-murine-model
#4
Soon-Young Lee, Chun-Sik Bae, Young-Hoon Choi, Nam-Sook Seo, Chang-Su Na, Jin-Cheol Yoo, Seung Sik Cho, Dae-Hun Park
Asthma is a chronic pulmonary disease that affects an estimated 235 million people worldwide, but asthma drugs have many adverse effects. Opuntia humifusa (eastern prickly pear) has been used as a food and traditional medicine worldwide; however, its anti-asthmatic effects have not been reported. We evaluated O. humifusa as a potential therapeutic or preventive component of anti-asthmatic drugs. We divided ovalbumin-sensitized mice into the following groups: normal control, asthma-induced control, dexamethasone-treated group (positive control), 50 mg/kg O...
2017: Food & Nutrition Research
https://www.readbyqxmd.com/read/29150431/the-e3-ubiquitin-ligase-apc-c-c-dh1-degrades-mcph1-after-mcph1-%C3%AE-trcp2-cdc25a-mediated-mitotic-entry-to-ensure-neurogenesis
#5
Xiaoqian Liu, Wen Zong, Tangliang Li, Yujun Wang, Xingzhi Xu, Zhong-Wei Zhou, Zhao-Qi Wang
Mutations of microcephalin (MCPH1) can cause the neurodevelopmental disorder primary microcephaly type 1. We previously showed that MCPH1 deletion in neural stem cells results in early mitotic entry that distracts cell division mode, leading to exhaustion of the progenitor pool. Here, we show that MCPH1 interacts with and promotes the E3 ligase βTrCP2 to degrade Cdc25A independent of DNA damage. Overexpression of βTrCP2 or the knockdown of Cdc25A remedies the high mitotic index and rescues the premature differentiation of Mcph1-deficient neuroprogenitors in vivo MCPH1 itself is degraded by APC/C(C)(dh1), but not APC/C(C)(dc20), in late mitosis and G1 phase...
November 17, 2017: EMBO Journal
https://www.readbyqxmd.com/read/29150278/a-hypothetical-role-for-notch-signaling-pathway-in-immunopathogenesis-of-leprosy
#6
Héctor Serrano-Coll, Liliana Acevedo-Saenz, Nora Cardona-Castro
Leprosy is a chronic infectious disease caused by Mycobacterium leprae mainly affecting skin and peripheral nerves. Leprosy has a broad range of clinical manifestations that range from mild (tuberculoid leprosy) to severe (lepromatous leprosy) forms, and are highly dependent on the host's immune response. Among the immune response elements involved in the pathogenesis of leprosy are the Toll-like receptors (TLRs), vitamin D receptor (VDR), natural killer cells (NK), and T cells. These innate and adaptive immune response elements may be related to the Notch signaling pathway, which is involved in immune cell growth, differentiation, and proliferation...
November 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/29150240/dichotomous-expression-of-tnf-superfamily-ligands-on-antigen-presenting-cells-controls-post-priming-anti-viral-cd4-t-cell-immunity
#7
Yu-Han Chang, Kuan Chung Wang, Kuan-Lun Chu, Derek L Clouthier, Anh T Tran, Miguel S Torres Perez, Angela C Zhou, Ali A Abdul-Sater, Tania H Watts
T cell antigen-presenting cell (APC) interactions early during chronic viral infection are crucial for determining viral set point and disease outcome, but how and when different APC subtypes contribute to these outcomes is unclear. The TNF receptor superfamily (TNFRSF) member GITR is important for CD4(+) T cell accumulation and control of chronic lymphocytic choriomeningitis virus (LCMV). We found that type I interferon (IFN-I) induced TNFSF ligands GITRL, 4-1BBL, OX40L, and CD70 predominantly on monocyte-derived APCs and CD80 and CD86 predominantly on classical dendritic cells (cDCs)...
November 13, 2017: Immunity
https://www.readbyqxmd.com/read/29149259/pancreatic-cancer-incidence-trends-evidence-from-the-surveillance-epidemiology-and-end-results-seer-population-based-data
#8
Vanessa L Gordon-Dseagu, Susan S Devesa, Michael Goggins, Rachael Stolzenberg-Solomon
Background: Annual pancreatic cancer incidence rates have been increasing. We examine pancreatic cancer incidence trends by demographics and histologic type. Methods: Data from the Surveillance, Epidemiology and End Results (SEER) registries were available to assess temporal trends and pancreatic cancer rates from 1974 to 2013. Results: Pancreatic cancer incidence rates declined between the 1970s and 1990s but increased from 1994 to 2013 among White males...
November 14, 2017: International Journal of Epidemiology
https://www.readbyqxmd.com/read/29148535/the-role-of-apc-in-wnt-pathway-activation-in-serrated-neoplasia
#9
Jennifer Borowsky, Troy Dumenil, Mark Bettington, Sally-Ann Pearson, Catherine Bond, Lochlan Fennell, Cheng Liu, Diane McKeone, Christophe Rosty, Ian Brown, Neal Walker, Barbara Leggett, Vicki Whitehall
Conventional adenomas are initiated by APC gene mutation that activates the WNT signal. Serrated neoplasia is commonly initiated by BRAF or KRAS mutation. WNT pathway activation may also occur, however, to what extent this is owing to APC mutation is unknown. We examined aberrant nuclear β-catenin immunolocalization as a surrogate for WNT pathway activation and analyzed the entire APC gene coding sequence in serrated and conventional pathway polyps and cancers. WNT pathway activation was a common event in conventional pathway lesions with aberrant nuclear immunolocalization of β-catenin and truncating APC mutations in 90% and 89% of conventional adenomas and 82% and 70% of BRAF wild-type cancers, respectively...
November 17, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29147609/tumor-immunology-meets%C3%A2-immunology-modified-cancer-cells-as-professional-apc-for-priming-na%C3%A3-ve-tumor-specific-cd4-t-cells
#10
REVIEW
Farah Bou Nasser Eddine, Elise Ramia, Giovanna Tosi, Greta Forlani, Roberto S Accolla
Although recent therapeutic approaches have revitalized the enthusiasm of the immunological way to combat cancer, still the comprehension of immunity against tumors is largely incomplete. Due to their specific function, CD8+ T cells with cytolytic activity (CTL) have attracted the attention of most investigators because CTL are considered the main effectors against tumor cells. Nevertheless, CTL activity and persistence is largely dependent on the action of CD4+ T helper cells (TH). Thus establishment of tumor-specific TH cell response is key to the optimal response against cancer...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29147008/the-transcription-factor-batf3-inhibits-the-differentiation-of-regulatory-t-cells-in-the-periphery
#11
Wonyong Lee, Hyeong Su Kim, Soo Seok Hwang, Gap Ryol Lee
Naive CD4 T cells activated by antigen-presenting cells (APCs) undergo terminal differentiation in the periphery. Multiple mechanisms determine their fates, that is, whether they differentiate into conventional T (Tconv) cells or regulatory T (Treg) cells. The key event during Treg generation is expression of the transcription factor Foxp3, which is the lineage-determining regulator for Treg differentiation and function. Here we show that the transcription factor Batf3 acts as a fate-decision factor with respect to Tconv versus Tregs by restraining Treg differentiation...
November 17, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29146772/cre-dependent-cas9-expressing-pigs-enable-efficient-in-vivo-genome-editing
#12
Kepin Wang, Qin Jin, Degong Ruan, Yi Yang, Qishuai Liu, Han Wu, Zhiwei Zhou, Zhen Ouyang, Zhaoming Liu, Yu Zhao, Bentian Zhao, Quanjun Zhang, Jiangyun Peng, Chengdan Lai, Nana Fan, Yanhui Liang, Ting Lan, Nan Li, Xiaoshan Wang, Xinlu Wang, Yong Fan, Pieter A Doevendans, Joost P G Sluijter, Pentao Liu, Xiaoping Li, Liangxue Lai
Despite being time-consuming and costly, generating genome-edited pigs holds great promise for agricultural, biomedical, and pharmaceutical applications. To further facilitate genome editing in pigs, we report here establishment of a pig line with Cre-inducible Cas9 expression that allows a variety of ex vivo genome editing in fibroblast cells including single- and multigene modifications, chromosome rearrangements, and efficient in vivo genetic modifications. As a proof of principle, we were able to simultaneously inactivate five tumor suppressor genes (TP53, PTEN, APC, BRCA1, and BRCA2) and activate one oncogene (KRAS), achieved by delivering Cre recombinase and sgRNAs, which caused rapid lung tumor development...
November 16, 2017: Genome Research
https://www.readbyqxmd.com/read/29144570/lncapc-drives-wnt-%C3%AE-catenin-activation-and-liver-tic-self-renewal-through-ezh2-mediated-apc-transcriptional-inhibition
#13
Xiaomin Fu, Jizhen Lin, Fujun Qin, Zihe Yang, Yuechao Ding, Yong Zhang, Lu Han, Xiaoyan Zhu, Qinxian Zhang
Liver tumor initiating cells (TICs), a small subset cells in tumor bulk, are responsible for liver tumor initiation, metastasis and relapse. However, the regulatory mechanism of liver TICs remains largely unknown. Here we found a long noncoding RNA lncAPC, locating near from APC locus, was highly expressed in liver cancer and liver TICs. LncAPC was required for liver TIC self-renewal. Silencing and overexpressing lncAPC showed impaired and enhanced sphere formation capacity of liver TICs, respectively. By recruiting EZH2 to APC promoter, LncAPC inhibits APC transcription and thus drives the activation of Wnt/β-catenin signaling...
November 16, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/29142207/phosphorylation-dynamics-dominate-the-regulated-proteome-during-early-xenopus-development
#14
Elizabeth H Peuchen, Olivia F Cox, Liangliang Sun, Alex S Hebert, Joshua J Coon, Matthew M Champion, Norman J Dovichi, Paul W Huber
The earliest stages of animal development are largely controlled by changes in protein phosphorylation mediated by signaling pathways and cyclin-dependent kinases. In order to decipher these complex networks and to discover new aspects of regulation by this post-translational modification, we undertook an analysis of the X. laevis phosphoproteome at seven developmental stages beginning with stage VI oocytes and ending with two-cell embryos. Concurrent measurement of the proteome and phosphoproteome enabled measurement of phosphosite occupancy as a function of developmental stage...
November 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29140293/the-trends-in-cardiovascular-diseases-and-respiratory-diseases-mortality-in-urban-and-rural-china-1990-2015
#15
Weiwei Sun, Yun Zhou, Zhuang Zhang, Limin Cao, Weihong Chen
With the rapid development of the economy over the past 20 years, the mortality rates from cardiovascular diseases (CVDs) and respiratory diseases (RDs) have changed in China. This study aimed to analyze the trends of mortality rates and years of life lost (YLLs) from CVDs and RDs in the rural and urban population from 1990 to 2015. Using data from Chinese yearbooks, joinpoint regression analysis was employed to estimate the annual percent change (APC) of mortality rates from CVDs and RDs. YLLs due to CVDs and RDs were calculated by a standard method, adopting recommended standard life expectancy at birth values of 80 years for men and 82...
November 15, 2017: International Journal of Environmental Research and Public Health
https://www.readbyqxmd.com/read/29136125/effective-connectivity-measured-using-optogenetically-evoked-hemodynamic-signals-exhibits-topography-distinct-from-resting-state-functional-connectivity-in-the-mouse
#16
Adam Q Bauer, Andrew W Kraft, Grant A Baxter, Patrick W Wright, Matthew D Reisman, Annie R Bice, Jasmine J Park, Michael R Bruchas, Abraham Z Snyder, Jin-Moo Lee, Joseph P Culver
Brain connectomics has expanded from histological assessment of axonal projection connectivity (APC) to encompass resting state functional connectivity (RS-FC). RS-FC analyses are efficient for whole-brain mapping, but attempts to explain aspects of RS-FC (e.g., interhemispheric RS-FC) based on APC have been only partially successful. Neuroimaging with hemoglobin alone lacks specificity for determining how activity in a population of cells contributes to RS-FC. Wide-field mapping of optogenetically defined connectivity could provide insights into the brain's structure-function relationship...
November 9, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/29135265/evaluation-of-early-therapeutic-effects-after-near-infrared-photoimmunotherapy-nir-pit-using-luciferase-luciferin-photon-counting-and-fluorescence-imaging
#17
Yasuhiro Maruoka, Tadanobu Nagaya, Yuko Nakamura, Kazuhide Sato, Fusa Ogata, Shuhei Okuyama, Peter L Choyke, Hisataka Kobayashi
Near infrared photoimmunotherapy (NIR-PIT) is a newly-developed cancer treatment that induces highly selective immunogenic cell death. It is based on an antibody-photo-absorber conjugate (APC) that is activated by NIR light. The purpose of this study was to investigate the effects of NIR-PIT as measured by luciferase-luciferin photon-counting and fluorescence imaging. Six days after subcutaneous injection of A431-luc-GFP cells tumors formed in a xenograft mouse model. The EGFR-targeting antibody, panitumumab was conjugated to the photoabsorber, IRDye-700DX (pan-IR700) and was intravenously administered to tumor-bearing mice...
November 14, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29133898/intertwining-dna-rna-nanocapsules-loaded-with-tumor-neoantigens-as-synergistic-nanovaccines-for-cancer-immunotherapy
#18
Guizhi Zhu, Lei Mei, Harshad D Vishwasrao, Orit Jacobson, Zhantong Wang, Yijing Liu, Bryant C Yung, Xiao Fu, Albert Jin, Gang Niu, Qin Wang, Fuwu Zhang, Hari Shroff, Xiaoyuan Chen
Nanomedicines that co-deliver DNA, RNA, and peptide therapeutics are highly desirable yet remain underdeveloped for cancer theranostics. Herein, we report self-assembled intertwining DNA-RNA nanocapsules (iDR-NCs) that efficiently delivered synergistic DNA CpG and short hairpin RNA (shRNA) adjuvants, as well as tumor-specific peptide neoantigens into antigen presenting cells (APCs) in lymph nodes for cancer immunotherapy. These nanovaccines were prepared by (1) producing tandem CpG and shRNA via concurrent rolling circle replication and rolling circle transcription, (2) self-assembling CpG and shRNA into DNA-RNA microflowers, (3) shrinking microflowers into iDR-NCs using PEG-grafted cationic polypeptides, and (4) physically loading neoantigen into iDR-NCs...
November 14, 2017: Nature Communications
https://www.readbyqxmd.com/read/29133385/targeted-next-generation-sequencing-of-cancer-genes-in-poorly-differentiated-thyroid-cancer
#19
Tiemo S Gerber, Arno Schad, Nils Hartmann, Erik Springer, Ulrich Zechner, Thomas J Musholt
Poorly differentiated thyroid carcinoma (PDTC) is a rare malignancy with higher mortality than well-differentiated thyroid carcinoma. The histological diagnosis can be difficult as well as the therapy. Improved diagnosis and new targeted therapies require knowledge of DNA sequence changes in cancer-relevant genes. The TruSeq Amplicon Cancer Panel was used to screen cancer genomes from 25 PDTC patients for somatic single nucleotide variants in 48 genes known to represent mutational hotspots. A total of 4490 variants were found in 23 tissue samples of PDTC...
November 13, 2017: Endocrine Connections
https://www.readbyqxmd.com/read/29133301/taming-the-beast-control-of-apc-c-cdc20-dependent-destruction
#20
Pablo Lara-Gonzalez, Taekyung Kim, Arshad Desai
The anaphase-promoting complex/cyclosome (APC/C) is a large multisubunit ubiquitin ligase that triggers the metaphase-to-anaphase transition in the cell cycle by targeting the substrates cyclin B and securin for destruction. APC/C activity toward these two key substrates requires the coactivator Cdc20. To ensure that cells enter mitosis and partition their duplicated genome with high accuracy, APC/C(Cdc20) activity must be tightly controlled. Here, we discuss the mechanisms that regulate APC/C(Cdc20) activity both before and during mitosis...
November 13, 2017: Cold Spring Harbor Symposia on Quantitative Biology
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