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https://www.readbyqxmd.com/read/29352742/cambogin-suppresses-dextran-sulphate-sodium-induced-colitis-by-enhancing-treg-cell-stability-and-function
#1
Yue Lu, Na-Mi Kim, Yi-Wen Jiang, Hong Zhang, Dan Zheng, Fu-Xiang Zhu, Rui Liang, Bin Li, Hong-Xi Xu
BACKGROUND AND PURPOSE: Inflammatory bowel disease (IBD) is a chronic and relapsing inflammatory disorder of gastrointestinal tract, and the dysfunction of immune regulation plays a critical role in IBD. Reflecting the limited use of current drugs and therapies for IBD treatment, it is necessary to explore novel drugs or therapies for this disease. We investigated the effect of cambogin in a mouse model of dextran sulphate sodium (DSS)-induced colitis and whether cambogin attenuates inflammation via Treg-cell-mediated immune modulation...
January 20, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29352646/synthesis-and-biological-evaluation-of-anti-cancer-agents-that-selectively-inhibit-her2-over-expressed-breast-cancer-cell-growth-via-down-regulation-of-her2-protein
#2
Anran Zhao, Qiaoyun Zheng, Cody M Orahoske, Nethrie D Idippily, Morgan M Ashcraft, Aicha Quamine, Bin Su
Compound JCC76 selectively inhibited the proliferation of human epidermal growth factor 2 (Her2) over-expressed breast cancer cells. In the current study, a ligand based structural optimization was performed to generate new analogs, and we identified derivatives 16 and 17 that showed improved activity and selectivity against Her2 positive breast cancer cells. A structure activity relationship (SAR) was summarized. Compounds 16 and 17 were also examined by western blot assay to check their effect on Her2 protein...
January 12, 2018: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29352264/cell-autonomous-role-of-iaspp-deficiency-in-causing-cardiocutaneous-disorders
#3
Zinaida Dedeić, Gopinath Sutendra, Ying Hu, Kathryn Chung, Elizabeth A Slee, Michael J White, Felix Y Zhou, Robert D Goldin, David J P Ferguson, Debra McAndrew, Jurgen E Schneider, Xin Lu
Desmosome components are frequently mutated in cardiac and cutaneous disorders in animals and humans and enhanced inflammation is a common feature of these diseases. Previous studies showed that inhibitor of Apoptosis Stimulating p53 Protein (iASPP) regulates desmosome integrity at cell-cell junctions and transcription in the nucleus, and its deficiency causes cardiocutaneous disorder in mice, cattle, and humans. As iASPP is a ubiquitously expressed shuttling protein with multiple functions, a key question is whether the observed cardiocutaneous phenotypes are caused by loss of a cell autonomous role of iASPP in cardiomyocytes and keratinocytes specifically or by a loss of iASPP in other cell types such as immune cells...
January 19, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29352251/differential-effects-of-sumo1-and-sumo3-on-pkr-activation-and-stability
#4
Ghizlane Maarifi, Faten El Asmi, Mohamed Ali Maroui, Laurent Dianoux, Mounira K Chelbi-Alix
Double-stranded RNA (dsRNA)-dependent protein kinase (PKR) is a serine/threonine kinase that exerts its own phosphorylation and the phosphorylation of the α subunit of the protein synthesis initiation factor eIF-2α. PKR was identified as a target of SUMOylation and the triple PKR-SUMO deficient mutant on Lysine residues K60-K150-K440 has reduced PKR activity. We report that SUMO1 and SUMO3 expression exert differential effects on PKR localization, activation and stability. SUMO1 or SUMO3 did not alter the repartition of PKR in the cytoplasm and the nucleus...
January 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29352246/u-box-ubiquitin-ligase-ppil2-suppresses-breast-cancer-invasion-and-metastasis-by-altering-cell-morphology-and-promoting-snai1-ubiquitination-and-degradation
#5
Zhaojun Jia, Miao Wang, Shujing Li, Xiahui Li, Xiao-Yan Bai, Zhaowei Xu, Yangyang Yang, Bowen Li, Yanan Li, Huijian Wu
Metastasis is the leading cause of breast cancer fatalities. To develop new therapeutic strategies, the mechanisms underlying breast cancer invasion and metastasis need to be further investigated. Peptidylprolyl isomerase (cyclophilin)-like 2 (PPIL2) is a U-box-type E3 ubiquitin ligase belonging to the cyclophilin family. Proteins within this family are the major cytosolic binding proteins of the immunosuppressant drug cyclosporine A (CsA). Although PPIL2 has been reported to potentially be involved in cell migration, its role in breast cancer is still unclear...
January 19, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29352242/ptre-seq-reveals-mechanism-and-interactions-of-rna-binding-proteins-and-mirnas
#6
Kyle A Cottrell, Hemangi G Chaudhari, Barak A Cohen, Sergej Djuranovic
RNA binding proteins (RBP) and microRNAs (miRNAs) often bind sequences in 3' untranslated regions (UTRs) of mRNAs, and regulate stability and translation efficiency. With the identification of numerous RBPs and miRNAs, there is an urgent need for new technologies to dissect the function of the cis-acting elements of RBPs and miRNAs. We describe post-transcriptional regulatory element sequencing (PTRE-seq), a massively parallel method for assaying the target sequences of miRNAs and RBPs. We use PTRE-seq to dissect sequence preferences and interactions between miRNAs and RBPs...
January 19, 2018: Nature Communications
https://www.readbyqxmd.com/read/29352198/orid-structure-controls-repd-initiation-during-rolling-circle-replication
#7
Algirdas Toleikis, Martin R Webb, Justin E Molloy
Bacterial antibiotic resistance is often carried by circular DNA plasmids that are copied separately from the genomic DNA and can be passed to other bacteria, spreading the resistance. The chloramphenicol-resistance plasmid pC221 from Staphylococcus aureus is duplicated by a process called asymmetric rolling circle replication. It is not fully understood how the replication process is regulated but its initiation requires a plasmid-encoded protein called RepD that nicks one strand of the parent plasmid at the double-stranded origin of replication (oriD)...
January 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29352156/comprehensive-reduction-of-amino-acid-set-in-a-protein-suggests-the-importance-of-prebiotic-amino-acids-for-stable-proteins
#8
Rei Shibue, Takahiro Sasamoto, Masami Shimada, Bowen Zhang, Akihiko Yamagishi, Satoshi Akanuma
Modern organisms commonly use the same set of 20 genetically coded amino acids for protein synthesis with very few exceptions. However, earlier protein synthesis was plausibly much simpler than modern one and utilized only a limited set of amino acids. Nevertheless, few experimental tests of this issue with arbitrarily chosen amino acid sets had been reported prior to this report. Herein we comprehensively and systematically reduced the size of the amino acid set constituting an ancestral nucleoside kinase that was reconstructed in our previous study...
January 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29352114/binding-of-nufip2-to-roquin-promotes-recognition-and-regulation-of-icos-mrna
#9
Nina Rehage, Elena Davydova, Christine Conrad, Gesine Behrens, Andreas Maiser, Jenny E Stehklein, Sven Brenner, Juliane Klein, Aicha Jeridi, Anne Hoffmann, Eunhae Lee, Umberto Dianzani, Rob Willemsen, Regina Feederle, Kristin Reiche, Jörg Hackermüller, Heinrich Leonhardt, Sonia Sharma, Dierk Niessing, Vigo Heissmeyer
The ubiquitously expressed RNA-binding proteins Roquin-1 and Roquin-2 are essential for appropriate immune cell function and postnatal survival of mice. Roquin proteins repress target mRNAs by recognizing secondary structures in their 3'-UTRs and by inducing mRNA decay. However, it is unknown if other cellular proteins contribute to target control. To identify cofactors of Roquin, we used RNA interference to screen ~1500 genes involved in RNA-binding or mRNA degradation, and identified NUFIP2 as a cofactor of Roquin-induced mRNA decay...
January 19, 2018: Nature Communications
https://www.readbyqxmd.com/read/29352075/o-linked-%C3%AE-n-acetylglucosamine-o-glcnac-modification-a-new-pathway-to-decode-pathogenesis-of-diabetic-retinopathy
#10
REVIEW
Zafer Gurel, Nader Sheibani
The incidence of diabetes continues to rise among all ages and ethnic groups worldwide. Diabetic retinopathy (DR) is a complication of diabetes that affects the retinal neurovasculature causing serious vision problems, including blindness. Its pathogenesis and severity is directly linked to the chronic exposure to high glucose conditions. No treatments are currently available to stop the development and progression of DR. To develop new and effective therapeutic approaches, it is critical to better understand how hyperglycemia contributes to the pathogenesis of DR at the cellular and molecular levels...
January 31, 2018: Clinical Science (1979-)
https://www.readbyqxmd.com/read/29351511/chemogenetic-tools-for-causal-cellular-and-neuronal-biology
#11
Deniz Atasoy, Scott M Sternson
Chemogenetic technologies enable selective pharmacological control of specific cell populations. An increasing number of approaches have been developed that modulate different signaling pathways. Selective pharmacological control over G protein-coupled receptor signaling, ion channel conductances, protein association, protein stability, and small molecule targeting allows modulation of cellular processes in distinct cell types. Here, we review these chemogenetic technologies and instances of their applications in complex tissues in vivo and ex vivo...
January 1, 2018: Physiological Reviews
https://www.readbyqxmd.com/read/29351238/telomeres-implications-for-cancer-development
#12
REVIEW
Aina Bernal, Laura Tusell
Telomeres facilitate the protection of natural ends of chromosomes from constitutive exposure to the DNA damage response (DDR). This is most likely achieved by a lariat structure that hides the linear telomeric DNA through protein-protein and protein-DNA interactions. The telomere shortening associated with DNA replication in the absence of a compensatory mechanism culminates in unmasked telomeres. Then, the subsequent activation of the DDR will define the fate of cells according to the functionality of cell cycle checkpoints...
January 19, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29350614/lipg-signaling-promotes-tumor-initiation-and-metastasis-of-human-basal-like-triple-negative-breast-cancer
#13
Pang-Kuo Lo, Yuan Yao, Ji Shin Lee, Yongshu Zhang, Weiliang Huang, Maureen A Kane, Qun Zhou
Current understanding of aggressive human basal-like triple-negative breast cancer (TNBC) remains incomplete. In this study, we show endothelial lipase (LIPG) is aberrantly overexpressed in basal-like TNBCs. We demonstrate that LIPG is required for in vivo tumorigenicity and metastasis of TNBC cells. LIPG possesses a lipase-dependent function that supports cancer cell proliferation and a lipase-independent function that promotes invasiveness, stemness and basal/epithelial-mesenchymal transition features of TNBC...
January 19, 2018: ELife
https://www.readbyqxmd.com/read/29349512/photobiomodulation-induces-in-vitro-re-epithelialization-via-nitric-oxide-production
#14
Manuela Rizzi, Mario Migliario, Stelvio Tonello, Vincenzo Rocchetti, Filippo Renò
Photobiomodulation is a widely used tool in regenerative medicine thanks to its ability to modulate a plethora of physiological responses. Wound re-epithelialization is strictly regulated by locally produced chemical mediators, such as nitric oxide (NO), a highly reactive free radical generated by the nitric oxide synthase (NOS) enzymatic family. In this study, it has been hypothesized that a 980-nm low-level laser stimulation could increase NO production in human keratinocytes and that such event might be directly related to the re-epithelialization process...
January 18, 2018: Lasers in Medical Science
https://www.readbyqxmd.com/read/29349490/auto-aggregation-properties-of-a-novel-aerobic-denitrifier-enterobacter-sp-strain-fl
#15
Xia Wang, Qiang An, Bin Zhao, Jin Song Guo, Yuan Sheng Huang, Meng Tian
Enterobacter sp. strain FL was newly isolated from activated sludge and exhibited significant capability of auto-aggregation as well as aerobic denitrification. The removal efficiencies of NO3--N, total nitrogen (TN), and TOC by strain FL in batch culture reached 94.6, 63.9, and 72.5% in 24 h, respectively. The production of N2O and N2 in the presence of oxygen demonstrated the occurrence of aerobic denitrification. The auto-aggregation index of strain FL reached 54.3%, suggesting a high tendency that the cells would agglomerate into aggregates...
January 18, 2018: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/29349463/stability-and-digestibility-of-one-or-bi-layered-medium-chain-triglyceride-emulsions-with-gum-arabic-and-whey-protein-isolates-by-pancreatic-lipase-in-vitro
#16
Xiaolin Yao, Yu Chen, Meng Shu, Kun Zhang, Zhiming Gao, Ying Kuang, Yapeng Fang, Katsuyoshi Nishinari, Glyn O Phillips, Fatang Jiang
Interfacial engineering approaches have been used to design functional foods so as to control lipase-induced digestion of emulsified lipids and release of bioactive lipophilic components in the gastrointestinal tract. In this study, emulsion droplets with the interface stabilized with gum Arabic (GA) and whey protein isolate (WPI) were prepared by mixing or sequential adsorption. WPI/GA intramolecular soluble complexes (ISCs) have superior emulsifying properties in stabilizing oil-in-water emulsions. The impact of the interfaces for WPI/GA ISC-layered (one-layered) and double-layered emulsions formed by sequential deposition of WPI or GA on the lipolysis of emulsions was investigated using an in vitro simulated gastrointestinal model...
January 19, 2018: Food & Function
https://www.readbyqxmd.com/read/29348634/a-biosensor-based-framework-to-measure-latent-proteostasis-capacity
#17
Rebecca J Wood, Angelique R Ormsby, Mona Radwan, Dezerae Cox, Abhishek Sharma, Tobias Vöpel, Simon Ebbinghaus, Mikael Oliveberg, Gavin E Reid, Alex Dickson, Danny M Hatters
The pool of quality control proteins (QC) that maintains protein-folding homeostasis (proteostasis) is dynamic but can become depleted in human disease. A challenge has been in quantitatively defining the depth of the QC pool. With a new biosensor, flow cytometry-based methods and mathematical modeling we measure the QC capacity to act as holdases and suppress biosensor aggregation. The biosensor system comprises a series of barnase kernels with differing folding stability that engage primarily with HSP70 and HSP90 family proteins...
January 18, 2018: Nature Communications
https://www.readbyqxmd.com/read/29348555/novel-immunoinformatics-approaches-to-design-multi-epitope-subunit-vaccine-for-malaria-by-investigating-anopheles-salivary-protein
#18
Rajan Kumar Pandey, Tarun Kumar Bhatt, Vijay Kumar Prajapati
Malaria fever has been pervasive for quite a while in tropical developing regions causing high morbidity and mortality. The causal organism is a protozoan parasite of genus Plasmodium which spreads to the human host by the bite of hitherto infected female Anopheles mosquito. In the course of biting, a salivary protein of Anopheles helps in blood feeding behavior and having the ability to elicit the host immune response. This study represents a series of immunoinformatics approaches to design multi-epitope subunit vaccine using Anopheles mosquito salivary proteins...
January 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29348456/twist1-induces-expression-of-discoidin-domain-receptor-2-to-promote-ovarian-cancer-metastasis
#19
Whitney R Grither, Laura M Divine, Eric H Meller, Daniel J Wilke, Riva A Desai, Andrew J Loza, Peinan Zhao, Anne Lohrey, Gregory D Longmore, Katherine C Fuh
The mesenchymal gene program has been shown to promote the metastatic progression of ovarian cancer; however, specific proteins induced by this program that lead to these metastatic behaviors have not been identified. Using patient derived tumor cells and established human ovarian tumor cell lines, we find that the Epithelial-to-Mesenchymal Transition inducing factor TWIST1 drives expression of discoidin domain receptor 2 (DDR2), a receptor tyrosine kinase (RTK) that recognizes fibrillar collagen as ligand...
January 19, 2018: Oncogene
https://www.readbyqxmd.com/read/29348454/harnessing-insulin-and-leptin-induced-oxidation-of-ptp1b-for-therapeutic-development
#20
Navasona Krishnan, Christopher A Bonham, Ioana A Rus, Om Kumar Shrestha, Carla M Gauss, Aftabul Haque, Ante Tocilj, Leemor Joshua-Tor, Nicholas K Tonks
The protein tyrosine phosphatase PTP1B is a major regulator of glucose homeostasis and energy metabolism, and a validated target for therapeutic intervention in diabetes and obesity. Nevertheless, it is a challenging target for inhibitor development. Previously, we generated a recombinant antibody (scFv45) that recognizes selectively the oxidized, inactive conformation of PTP1B. Here, we provide a molecular basis for its interaction with reversibly oxidized PTP1B. Furthermore, we have identified a small molecule inhibitor that mimics the effects of scFv45...
January 18, 2018: Nature Communications
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