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https://www.readbyqxmd.com/read/28231510/lipopolyplex-potentiates-anti-tumor-immunity-of-mrna-based-vaccination
#1
Stefano Persano, Maria L Guevara, Zhaoqi Li, Junhua Mai, Mauro Ferrari, Pier Paolo Pompa, Haifa Shen
mRNA-based vaccines have the benefit of triggering robust anti-cancer immunity without the potential danger of genome integration from DNA vaccines or the limitation of antigen selection from peptide vaccines. Yet, a conventional mRNA vaccine comprising of condensed mRNA molecules in a positively charged protein core structure is not effectively internalized by the antigen-presenting cells. It cannot offer sufficient protection for mRNA molecules from degradation by plasma and tissue enzymes either. Here, we have developed a lipopolyplex mRNA vaccine that consists of a poly-(β-amino ester) polymer mRNA core encapsulated into a 1,2-dioleoyl-sn-glycero-3-ethylphosphocholine/1,2-dioleoyl-sn-glycero-3-phosphatidyl-ethanolamine/1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)-2000 (EDOPC/DOPE/DSPE-PEG) lipid shell...
February 20, 2017: Biomaterials
https://www.readbyqxmd.com/read/28224650/androgen-receptor-splice-variants-are-not-substrates-of-nonsense-mediated-decay
#2
Atinuke S Ajiboye, David Esopi, Srinivasan Yegnasubramanian, Samuel R Denmeade
BACKGROUND: Androgen receptor (AR) splice variants have been clinically associated with progressive cancer, castration-resistance, and resistance to AR antagonists and androgen synthesis inhibitors. AR variants can be generated by genomic alterations and alternative splicing, and their expression is androgen-regulated. There has been a suggestion that AR variants bearing premature termination codons and coding for truncated proteins should be regulated by the nonsense-mediated decay (NMD) mRNA surveillance pathway, suggesting that either the NMD pathway is dysfunctional in variant-expressing cell lines or that variants are somehow able to evade degradation by NMD...
February 22, 2017: Prostate
https://www.readbyqxmd.com/read/28218725/treating-cancer-by-targeting-telomeres-and-telomerase
#3
REVIEW
Marko Ivancich, Zachary Schrank, Luke Wojdyla, Brandon Leviskas, Adijan Kuckovic, Ankita Sanjali, Neelu Puri
Telomerase is expressed in more than 85% of cancer cells. Tumor cells with metastatic potential may have a high telomerase activity, allowing cells to escape from the inhibition of cell proliferation due to shortened telomeres. Human telomerase primarily consists of two main components: hTERT, a catalytic subunit, and hTR, an RNA template whose sequence is complimentary to the telomeric 5'-dTTAGGG-3' repeat. In humans, telomerase activity is typically restricted to renewing tissues, such as germ cells and stem cells, and is generally absent in normal cells...
February 19, 2017: Antioxidants (Basel, Switzerland)
https://www.readbyqxmd.com/read/28214861/sirt1-regulates-the-inflammatory-response-of-vascular-adventitial-fibroblasts-through-autophagy-and-related-signaling-pathway
#4
Wei-Rong Wang, Ting-Ting Li, Ting Jing, Yan-Xiang Li, Xiao-Feng Yang, Yan-Hao He, Wei Zhang, Rong Lin, Ji-Ye Zhang
BACKGROUND/AIMS: Autophagy is a lysosomal degradation pathway that is essential for cellular survival, differentiation, and homeostasis. Sirtuin 1 (SIRT1), a NAD+-dependent deacetylase, plays a pivotal role in modulation of autophagy. Recent studies found that autophagy was involved in the regulation of inflammatory response. In this study, we aimed to determine the effect of SIRT1 on autophagy and inflammation, and whether autophagy can regulate the inflammatory response in vascular adventitial fibroblasts (VAFs)...
February 3, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28214847/contribution-of-p62-to-phenotype-transition-of-coronary-arterial-myocytes-with-defective-autophagy
#5
Junxiang Bao, Guangbi Li, Xinxu Yuan, Erich Gulbins, Pin-Lan Li
BACKGROUND: Autophagy disorder contributes to dedifferentiation of arterial smooth muscle cells, but the mechanisms are poorly understood. Here, we sought to investigate the role of scaffolding adaptor p62/SQSTM1 (p62) in phenotype switching of mouse coronary arterial myocytes (CAMs) induced by CD38 gene deficiency or lysosomal dysfunction which blocks autophagic flux in the cells. METHODS: Protein expression was measured by western blot analysis and immunofluorescent staining...
3, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28214521/neuroprotective-effect-of-salvianolic-acid-b-against-cerebral-ischemic-injury-in-rats-via-the-cd40-nf-%C3%AE%C2%BAb-pathway-associated-with-suppression-of-platelets-activation-and-neuroinflammation
#6
Shixin Xu, Aiqin Zhong, Huining Ma, Dan Li, Yue Hu, Yingzhi Xu, Junping Zhang
Neuroinflammation plays a critical role in the pathogenesis of ischemia/reperfusion (I/R) injury. Activated platelets are increasingly regarded as initiators and/or amplifiers of inflammatory processes in cerebral I/R injury. Salvianolic acid B (SAB) is the most abundant bioactive compound of Salviae miltiorrhizae, a well-known Chinese herb used to promote blood circulation and eliminating blood stasis. S. miltiorrhizae has been used clinically in Asia for the treatment of ischemic cerebrovascular diseases...
February 15, 2017: Brain Research
https://www.readbyqxmd.com/read/28213540/characterization-of-the-physical-and-functional-interplay-between-mazf1-bif-and-its-noncognate-antitoxins-from-bifidobacterium-longum
#7
Yanxia Wei, Yang Li, Fan Yang, Qiong Wu, Dianbin Liu, Xiangyang Li, Hui Hua, Xiaomei Liu, Yugang Wang, Kuiyang Zheng, Renxian Tang
Bifidobacterium longum strain JDM301, a widely used commercial strain in China, encodes at least two MazEF-like modules and one RelBE-like toxin-antitoxin (TA) systems in its chromosome, designated as MazE1F1(Bif), MazE2F2(Bif) and RelBE(Bif), respectively. Bacterial TA systems play an important role in several stress responses, but the relationship between these TA systems is largely unknown. In this study, the interaction between MazF1(Bif) and MazE2(Bif) or RelB(Bif) was assessed in B. longum strain JDM301...
February 17, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28213287/butein-induction-of-ho-1-by-p38-mapk-nrf2-pathway-in-adipocytes-attenuates-high-fat-diet-induced-adipose-hypertrophy-in-mice
#8
Zheng Wang, Sun-O Ka, Youngyi Lee, Byung-Hyun Park, Eun Ju Bae
Adipose tissue inflammation and oxidative stress are key components in the development of obesity and insulin resistance. Heme oxygenase (HO)-1 in adipocytes protects against obesity and adipose dysfunction. In this study, we report the identification of butein, a flavonoid chalcone, as a novel inducer of HO-1 expression in adipocytes in vitro and in vivo. Butein upregulated HO-1 mRNA and protein expression in 3T3-L1 adipocytes, accompanied by Kelch-Like ECH-Associated Protein (Keap) 1 degradation and increase in the nuclear level of nuclear factor erythroid 2-related factor 2 (Nrf2)...
February 14, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28213268/fisetin-inhibits-il-1%C3%AE-induced-inflammatory-response-in-human-osteoarthritis-chondrocytes-through-activating-sirt1-and-attenuates-the-progression-of-osteoarthritis-in-mice
#9
Wenhao Zheng, Zhenhua Feng, Shengban You, Hui Zhang, Zhenyu Tao, Quan Wang, Hua Chen, Yaosen Wu
Osteoarthritis (OA) is a degenerative joint disease characterized by cartilage degradation and inflammation. Fisetin, a polyphenol extracted from fruits and vegetables, has been reported to have anti-inflammatory effects. Our study aimed to investigate the effect of fisetin on OA both in vitro and in vivo. In vitro, chondrocytes were pretreated with fisetin alone or fisetin combined with sirtinol (an inhibitor of SIRT1) for 2h before IL-1β stimulation. Production of NO, PGE2, TNF-α and IL-6 were evaluated by the Griess reaction and ELISAs...
February 14, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28213129/cyclic-compressive-stress-induced-scinderin-regulates-progress-of-developmental-dysplasia-of-the-hip
#10
Cheng-Long Wang, Hui Wang, Fei Xiao, Chuan-Dong Wang, Guo-Li Hu, Jun-Feng Zhu, Chao Shen, Bin Zuo, Yi-Min Cui, De Li, Yuan-Gao, Xiao-Ling Zhang, Xiao-Dong Chen
Developmental dysplasia of the hip (DDH) is a common musculoskeletal disorder characterized by a mismatch between acetabulum and femoral head. Mechanical force plays an important role during the occurrence and development of abnormities in acetabulum and femoral head. In this study, we established a mechanical force model named cyclic compressive stress (Ccs). To analyze the effect of Ccs on DDH, we detected special genes in chondrocytes and osteoblasts. Results showed that Ccs downregulated chondrogenesis of ADTC5 in a concentration-dependent manner...
February 14, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28213042/gene-duplication-conservation-and-divergence-of-heme-oxygenase-2-genes-in-blunt-snout-bream-megalobrama-amblycephala-and-their-responses-to-hypoxia
#11
Xue-Li Zhang, Yi-Wen Sun, Jie Chen, Xia-Yun Jiang, Shu-Ming Zou
Heme oxygenase (HO) that catalyzes the degradation of heme, is involved in responding and using oxygen in teleost fish. Physiologic heme degradation can be catalyzed by two isozymes of HO (HO-1 and HO-2). In fish, the molecular constructions, expression characteristics and hypoxic regulation of HO-2 are still not well known. Here, we report the isolation and characterization of duplicated HO-2 genes in blunt snout bream, a hypoxia sensitive fish species. Blunt snout bream HO-2a and -2b genes shared a relatively low sequence identity of 67%...
February 14, 2017: Gene
https://www.readbyqxmd.com/read/28212427/rbm46-regulates-mouse-embryonic-stem-cell-differentiation-by-targeting-%C3%AE-catenin-mrna-for-degradation
#12
Lei Zhai, Chenchen Wang, Yuanfan Chen, Shixin Zhou, Lingsong Li
Embryonic stem cells (ESCs) are pluripotent cells and have the capability for differentiation into any of the three embryonic germ layers. The Wnt/β-Catenin pathway has been shown to play an essential role in ESC differentiation regulation. Activation of β-Catenin by post-translational modification has been extensively studied. However, mechanism(s) of post-transcriptional regulation of β-Catenin are not well defined. In this study, we report an RNA recognition motif-containing protein (RNA binding motif protein 46, RBM46) which regulates the degradation of β-Catenin mRNA...
2017: PloS One
https://www.readbyqxmd.com/read/28210969/host-tissue-response-by-the-expression-of-collagen-to-cyanoacrylate-adhesives-used-in-implant-fixation-for-abdominal-hernia-repair
#13
Gemma Pascual, Marta Rodríguez, Bárbara Pérez-Köhler, Claudia Mesa-Ciller, Mar Fernández-Gutiérrez, Julio San Román, Juan M Bellón
The less traumatic use of surgical adhesives rather than sutures for mesh fixation in hernia repair has started to gain popularity because they induce less host tissue damage and provoke less postoperative pain. This study examines the host tissue response to a new cyanoacrylate (CA) adhesive (n-octyl, OCA). Partial defects (3 × 5 cm) created in the rabbit anterior abdominal wall were repaired by mesh fixation using OCA, Glubran2(®)(n-butyl-CA), Ifabond(®)(n-hexyl-CA) or sutures. Samples were obtained at 14/90 days for morphology, collagens qRT-PCR/immunofluorescence and biomechanical studies...
April 2017: Journal of Materials Science. Materials in Medicine
https://www.readbyqxmd.com/read/28209709/pathogenic-mutations-in-retinitis-pigmentosa-2-predominantly-result-in-loss-of-rp2-protein-stability-in-human-and-zebrafish
#14
Fei Liu, Yayun Qin, Shanshan Yu, Dinesh C Soares, Lifang Yang, Jun Weng, Chang Li, Meng Gao, Zhaojing Lu, Xuebin Hu, Xiliang Liu, Tao Jiang, Jing Y Liu, Xinhua Shu, Zhaohui Tang, Mugen Liu
Mutations in retinitis pigmentosa 2 (RP2) account for 10-20% of X-linked retinitis pigmentosa (RP) cases. The encoded RP2 protein is implicated in ciliary trafficking of myristoylated and prenylated proteins in photoreceptor cells. To date, over 70 mutations in RP2 have been identified. How these mutations disrupt the function of RP2 is not fully understood. Here, we report a novel in-frame 12-bp deletion (c.357_368del, p.Pro120_Gly123del) in zebrafish rp2 The mutant zebrafish shows reduced rod phototransduction proteins and progressive retinal degeneration...
February 16, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28209269/association-of-matrix-metalloproteinase-levels-with-collagen-degradation-in-the-context-of-abdominal-aortic-aneurysm
#15
V Klaus, F Tanios-Schmies, C Reeps, M Trenner, E Matevossian, H-H Eckstein, J Pelisek
OBJECTIVE/BACKGROUND: Matrix metalloproteinases (MMPs) have already been identified as key players in the pathogenesis of abdominal aortic aneurysm (AAA). However, the current data remain inconclusive. In this study, the expression of MMPs at mRNA and protein levels were investigated in relation to the degradation of collagen I and collagen III. METHODS: Tissue samples were obtained from 40 patients with AAA undergoing open aortic repair, and from five healthy controls during kidney transplantation...
February 10, 2017: European Journal of Vascular and Endovascular Surgery
https://www.readbyqxmd.com/read/28208714/biodegradation-mechanisms-of-patulin-in-candida-guilliermondii-an-itraq-based-proteomic-analysis
#16
Yong Chen, Huai-Min Peng, Xiao Wang, Bo-Qiang Li, Man-Yuan Long, Shi-Ping Tian
Patulin, a potent mycotoxin, contaminates fruits and derived products worldwide, and is a serious health concern. Several yeast strains have shown the ability to effectively degrade patulin. However, the mechanisms of its biodegradation still remain unclear at this time. In the present study, biodegradation and involved mechanisms of patulin by an antagonistic yeast Candida guilliermondii were investigated. The results indicated that C. guilliermondii was capable of not only multiplying to a high population in medium containing patulin, but also effectively reducing patulin content in culture medium...
February 8, 2017: Toxins
https://www.readbyqxmd.com/read/28207754/ascofuranone-inhibits-lipopolysaccharide-induced-inflammatory-response-via-nf-kappab-and-ap-1-p-erk-tnf-%C3%AE-il-6-and-il-1%C3%AE-in-raw-264-7-macrophages
#17
Jun-Young Park, Tae-Wook Chung, Yun-Jeong Jeong, Choong-Hwan Kwak, Sun-Hyung Ha, Kyung-Min Kwon, Fukushi Abekura, Seung-Hak Cho, Young-Choon Lee, Ki-Tae Ha, Junji Magae, Young-Chae Chang, Cheorl-Ho Kim
The natural fungal compound ascofuranone (5-chloro-3-[(2E,6E)-7-[(2S)-5,5-dimethyl-4-oxo-tetrahydrofuran-2-yl]-3-methyl-octa-2,6-dienyl]-2,4-dihydroxy-6-methyl-benzaldehyde, MW 420.93) (AF) isolated from Ascochyta viciae has been known to promote cell cycle arrest and inhibit invasion of tumor cells. We have previously studied a structurally similar compound ascochlorin (ASC; MW 404.93) with regard to its anti-inflammatory activity in LPS- stimulated RAW 264.7 macrophages. In order to examine the relationship between the anti-inflammatory activities and the molecular differences between AF and ASC, the activity of AF is herein studied, because ASC has a unique trimethyl oxocyclohexyl structure, while AF has a unique dimethyl-oxo-tetrahydrofuran structure...
2017: PloS One
https://www.readbyqxmd.com/read/28207183/combining-the-auxin-inducible-degradation-system-with-crispr-cas9-based-genome-editing-for-the-conditional-depletion-of-endogenous-drosophila-melanogaster-proteins
#18
Melinda Bence, Ferenc Jankovics, Tamás Lukácsovich, Miklós Erdélyi
Inducible protein degradation techniques have considerable advantages over classical genetic approaches, which generate loss-of-function phenotypes at the gene or mRNA level. The plant-derived auxin-inducible degradation system (AID) is a promising technique which enables the degradation of target proteins tagged with the AID motif in non-plant cells. Here, we present a detailed characterization of this method employed during the adult oogenesis of Drosophila. Furthermore, with the help of CRISPR/Cas9-based genome editing, we improve the utility of the AID system in the conditional elimination of endogenously expressed proteins...
February 16, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28206953/zinc-finger-protein-zfp36l1-promotes-osteoblastic-differentiation-but-represses-adipogenic-differentiation-of-mouse-multipotent-cells
#19
Kuo-Yun Tseng, Yi-Hsuan Chen, Shankung Lin
Zinc finger protein 36, C3H type-like 1 (ZFP36L1) is a member of the tristetraprolin (TTP) family and its role in the aging-related bone loss is currently unknown. We present evidence that ZFP36L1 expression in rat femurs and bone marrow mesenchymal stem cells (bmMSCs) was down-regulated with aging. ZFP36L1 knockdown decreased osteoblastic differentiation of MC3T3-E1 and C3H10T1/2 cells, and increased adipogenic differentiation of 3T3-L1 and C3H10T1/2 cells, whereas ZFP36L1 overexpression did the opposite. The finding that ZFP36L1 overexpression enhanced osteoblastic and repressed adipogenic differentiation was also corroborated by ex vivo experiments...
February 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28205209/characterization-of-the-gnmt-hecth9-prex2-tripartite-relationship-in-the-pathogenesis-of-hepatocellular-carcinoma
#20
Chung-Hsien Li, Chia-Hung Yen, Yen-Fu Chen, Kuo-Jui Lee, Cheng-Chieh Fang, Xian Zhang, Chih-Chung Lai, Shiu-Feng Huang, Hui-Kuan Lin, Yi-Ming Arthur Chen
The pathogenesis of hepatocellular carcinoma (HCC) involves many molecular pathways. Glycine N-methyltransferase (GNMT) is downregulated in almost all HCC and its gene knockout mice developed HCC with high penetrance. We identified PREX2, a novel PTEN inhibitor, as a GNMT-interacting protein. Such interaction enhanced degradation of PREX2 through an E3 ligase HectH9-mediated proteasomal ubiquitination pathway. Depletion of GNMT or HectH9 resulted in AKT activation in a PREX2 dependent manner and enhanced cell proliferation...
February 16, 2017: International Journal of Cancer. Journal International du Cancer
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