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Ka-Yee Au, Wei-Wei Shi, Shuai Qian, Zhong Zuo, Pang-Chui Shaw
To improve the pharmacological properties of maize ribosome-inactivating protein (maize RIP) for targeting HIV-infected cells, the previously engineered TAT-fused active form of maize RIP (MOD) was further engineered for cysteine-directed PEGylation. In this work, two potential antigenic sites, namely Lys-78 and Lys-264, were identified. They were mutated to cysteine residue and conjugated with PEG5k or PEG20k. The resultant PEG derivatives of MOD variants were examined for ribosome-inactivating activity, circulating half-life and immunogenicity...
October 17, 2016: Toxins
Gillian Hertlein, Marlene Seiffert, Sebastian Gensel, Eva Garcia-Gonzalez, Julia Ebeling, Ranko Skobalj, Anja Kuthning, Roderich D Süssmuth, Elke Genersch
The Gram-positive bacterium Paenibacillus larvae (P. larvae) is the causative agent of a deadly honey bee brood disease called American Foulbrood (AFB). AFB is a notifiable epizootic in most countries and, hence, P. larvae is of considerable relevance for veterinarians and apiculturists alike. Over the last decade, much progress has been made in the understanding of the (patho)biology of P. larvae. Recently, several non-ribosomally produced peptides (NRP) and peptide/polyketide (NRP/PK) hybrids produced by P...
2016: PloS One
Min Pang, Xin-Yan Bai, Yan Li, Ji-Zhong Bai, Li-Rong Yuan, Shou-An Ren, Xiao-Yun Hu, Xin-Ri Zhang, Bao-Feng Yu, Rui Guo, Hai-Long Wang
Clara cell protein (CC16) is an anti-inflammatory protein, which is expressed in the airway epithelium. It is involved in the development of airway inflammatory diseases, including chronic obstructive pulmonary disease and asthma. However, the exact molecular mechanism underlying its anti‑inflammatory action remains to be fully elucidated. The aim of the present study was to define the protein profiles of the anti‑inflammatory effect of CC16 in lipopolysaccharide (LPS)‑treated rat tracheal epithelial (RTE) cells using shotgun proteomics...
October 12, 2016: Molecular Medicine Reports
Donna N Petersen, Julie Hawkins, Wanida Ruangsiriluk, Kimberly A Stevens, Bruce A Maguire, Thomas N O'Connell, Benjamin N Rocke, Markus Boehm, Roger B Ruggeri, Tim Rolph, David Hepworth, Paula M Loria, Philip A Carpino
Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a secreted protein that downregulates low-density lipoprotein (LDL) receptor (LDL-R) levels on the surface of hepatocytes, resulting in decreased clearance of LDL-cholesterol (LDL-C). Phenotypic screening of a small-molecule compound collection was used to identify an inhibitor of PCSK9 secretion, (R)-N-(isoquinolin-1-yl)-3-(4-methoxyphenyl)-N-(piperidin-3-yl)propanamide (R-IMPP), which was shown to stimulate uptake of LDL-C in hepatoma cells by increasing LDL-R levels, without altering levels of secreted transferrin...
October 13, 2016: Cell Chemical Biology
S Combes, K Massip, O Martin, H Furbeyre, L Cauquil, G Pascal, O Bouchez, N Le Floc'h, O Zemb, I P Oswald, T Gidenne
Limiting the post-weaning intake of the young rabbit is known to improve its resistance to digestive disorders, whereas a degradation of its housing hygiene is assumed to have a negative impact on its health. This study aims at providing insights into the mechanism of digestive health preservation regarding both host (growth and immune response) and its symbiotic digestive microbiota. A 2×2 factorial design from weaning (day 28) to day 64 was set up: ad libitum intake or restricted intake at 70% of ad libitum, and high v...
October 17, 2016: Animal: An International Journal of Animal Bioscience
Hsiang-Tsui Wang, Tzu-Ying Chen, Ching-Wen Weng, Chun-Hsiang Yang, Moon-Shong Tang
Acrolein (Acr) is a potent cytotoxic and DNA damaging agent which is ubiquitous in the environment and abundant in tobacco smoke. Acr is also an active cytotoxic metabolite of the anti-cancer drugs cyclophosphamide and ifosfamide. The mechanisms via which Acr exerts its anti-cancer activity and cytotoxicity are not clear. In this study, we found that Acr induces cytotoxicity and cell death in human cancer cells with different activities of p53. Acr preferentially binds nucleolar ribosomal DNA (rDNA) to form Acr-deoxyguanosine adducts, and induces oxidative damage to both rDNA and ribosomal RNA (rRNA)...
October 12, 2016: Oncotarget
Cherry Yin-Yi Chang, Ming-Tsung Lai, Yi Chen, Ching-Wen Yang, Hui-Wen Chang, Cheng-Chan Lu, Chih-Mei Chen, Carmen Chan, Ching Chung, Chun-Cheng Tseng, Tritium Hwang, Jim Jinn-Chyuan Sheu, Fuu-Jen Tsai
Aberrant miRNA expression has been reported in endometriosis and miRNA gene polymorphisms have been linked to cancer. Because certain ovarian cancers arise from endometriosis, we genotyped seven cancer-related miRNA single nucleotide polymorphisms (MiRSNPs) to investigate their possible roles in endometriosis. Genetic variants in MIR196A2 (rs11614913) and MIR100 (rs1834306) were found to be associated with endometriosis development and related clinical phenotypes, such as infertility and pain. Downstream analysis of the MIR196A2 risk allele revealed upregulation of rRNA editing and protein synthesis genes, suggesting hyper-activation of ribosome biogenesis as a driving force for endometriosis progression...
September 15, 2016: Oncotarget
Hui-Lu Zhang, Wen-Shuai Li, Dian-Nan Xu, Wan-Wei Zheng, Yi Liu, Jian Chen, Zhi-Bing Qiu, Robert G Dorfman, Jun Zhang, Jie Liu
Gut microbiota composition of patients with ulcerative colitis (UC) is markedly altered compared with healthy individuals. There is mounting evidence that probiotic therapy alleviates disease severity in animal models and patients with inflammatory bowel disease (IBD). Bacillus subtilisis, as a probiotic, has also demonstrated a protective effect in IBD. However, the therapeutic mechanism of its action has yet to be elucidated. In the present study, a dextrose sulfate sodium (DSS)-induced UC mouse model was used to investigate the role of B...
October 2016: Experimental and Therapeutic Medicine
Ayesha Kabir, Devawati Dutta, Chhabinath Mandal, Gopinatha Suresh Kumar
A major thrust of anticancer therapeutics is the dynamic quest for small molecules that binds and modifies nucleic acids and proteins effectively. The role of tRNA in the protein translational machinery and the influence of polyamines on the interaction of acylated and deacylated tRNA to ribosomes,47-48 make polyamine-tRNA interactions conspicuous. Therefore, we have studied the interaction of two biogenic polyamines spermine and spermidine with tRNAPhe and compared the interaction with the polyamine analog, 1-naphthyl acetyl spermine to fathom the thermodynamic and structural basis of the binding interaction...
October 3, 2016: Journal of Physical Chemistry. B
T Marrs, C Flohr
Conventional culture-based studies have suggested that a reduction in microbial exposure in early life predisposes to atopic eczema and allergies. However, molecular microbiological methods have shown that conventional culture fails to grow around 80% of the bacterial flora. More recent work reviewed in this paper has employed next generation sequencing to study the influence of the gut and skin microbiota, both with regard to the risk of developing atopic eczema but also the role of pathogenic and commensal bacteria in established disease...
October 2016: British Journal of Dermatology
Alexander G Myasnikov, S Kundhavai Natchiar, Marielle Nebout, Isabelle Hazemann, Véronique Imbert, Heena Khatter, Jean-François Peyron, Bruno P Klaholz
Many antibiotics in clinical use target the bacterial ribosome by interfering with the protein synthesis machinery. However, targeting the human ribosome in the case of protein synthesis deregulations such as in highly proliferating cancer cells has not been investigated at the molecular level up to now. Here we report the structure of the human 80S ribosome with a eukaryote-specific antibiotic and show its anti-proliferative effect on several cancer cell lines. The structure provides insights into the detailed interactions in a ligand-binding pocket of the human ribosome that are required for structure-assisted drug design...
2016: Nature Communications
Patricia M Legler, Jaimee R Compton, Martha L Hale, George P Anderson, Mark A Olson, Charles B Millard, Ellen R Goldman
Ricin is an A-B ribosome inactivating protein (RIP) toxin composed of an A-chain subunit (RTA) that contains a catalytic N-glycosidase and a B-chain (RTB) lectin domain that binds cell surface glycans. Ricin exploits retrograde transport to enter into the Golgi and the endoplasmic reticulum, and then dislocates into the cytoplasm where it can reach its substrate, the ribosomal RNA. A subset of isolated antibodies (Abs) raised against the RTA subunit protect against ricin intoxication, and RTA-based vaccine immunogens have been shown to provide long-lasting protective immunity against the holotoxin...
September 23, 2016: MAbs
Jing Xu, Ke-Qi Wang, Wei-Heng Xu, Ying-Hua Li, Yang Qi, Hong-Yuan Wu, Jian-Zhong Li, Zhi-Gao He, Hong-Gang Hu, Yan Wang, Jun-Ping Zhang
BACKGROUND:  MASM, a novel derivative of matrine, has inhibitory effect on activation of macrophages, dendritic cells and hepatic stellate cells and binds to ribosomal protein S5 (RPS5). This study was designed to evaluate effect of MASM on murine established lethal sepsis and its mechanisms. METHODS:  Mouse peritoneal macrophages and RAW264.7 cells that were infected with recombinant lentiviruses encoding shRPS5 were incubated with lipopolysaccharides (LPS) in the absence or presence of MASM in vitro...
September 22, 2016: Journal of Infectious Diseases
Arun K Mishra, Pragya Yadav, Amrita Mishra
The symptoms of Staphylococcal scalded skin syndrome (SSSS) include blistering of skin on superficial layers due to the exfoliative toxins released from Staphylococcus aureus. After the acute exfoliation of skin surface, erythematous cellulitis occurs. The SSSS may be confined to few blisters localized to the infection site and spread to severe exfoliation affecting complete body. The specific antibodies to exotoxins and increased clearence of exotoxins decrease the frequency of SSSS in adults. Immediate medication with parenteral anti-staphylococcal antibiotics is mandatory...
2016: Open Microbiology Journal
Hui-Jun Xu, Wei-Dan Jiang, Lin Feng, Yang Liu, Pei Wu, Jun Jiang, Sheng-Yao Kuang, Ling Tang, Wu-Neng Tang, Yong-An Zhang, Xiao-Qiu Zhou
This study explored the effects of vitamin C on the physical barriers and immune barriers, and relative mRNA levels of signaling molecules in the gill of grass carp (Ctenopharyngodon idella) under infection of Flavobacterium columnare. The results indicated that compared with optimal vitamin C supplementation, vitamin C deficiency (2.9 mg/kg diet) (1) increased reactive oxygen species, malondialdehyde and protein carbonyl (PC) contents (P < 0.05), decreased the copper/zinc superoxide dismutase, manganese superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase activities and mRNA levels (P < 0...
September 15, 2016: Fish & Shellfish Immunology
Lasse Jørgensen Cehofski, Anders Kruse, Martin Bøgsted, Sigriður Olga Magnusdottir, Allan Stensballe, Bent Honoré, Henrik Vorum
Animal models of experimental branch retinal vein occlusion (BRVO) provide a unique opportunity to study protein changes directly in retinal tissue. Results from these experimental models suggest that experimental BRVO is associated with an upregulation of extracellular matrix remodeling and adhesion signaling processes. To study whether these processes could be blocked by inhibition of VEGF-A, a porcine model of experimental BRVO was combined with proteomic analyses. In six Danish Landrace pigs experimental BRVO was induced with argon laser in both eyes...
September 9, 2016: Experimental Eye Research
Luanluan Shao, Chaochao Xu, Hongshuai Ji, Weiping Mao, Yingying Wang, Xiaoqian Liu, Yanyan Zhu
Objective To construct the ribosome display library of anti-B7-H4 extracellular domain, and select the antibody with high specificity. Methods The cDNA of B7-H4 extracellular domain was amplified from A549 cells by reverse transcription PCR (RT-PCR). To express ectodomains of B7-H4, the sequence of B7-H4 gene, which encodes the B7-H4 extracellular domains, was inserted into plasmid pET-28a(+). The purified recombinant protein of B7-H4 extracellular domain was used to immunize BALB/c mice. The total RNA was extracted from the spleen of BALB/c mice which had been immunized with B7-H4 recombinant protein...
September 2016: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
Chen Chen, Sun Xiaobo, Wang Yuge, Shu Yaqing, Fang Ling, Peng Lisheng, Lu Zhengqi, Qiu Wei
OBJECTIVE: To investigate the relationship between neuromyelitis optica spectrum disorder (NMOSD) and autoantibodies. METHODS: Blood samples of 108 NMOSD patients and 38 controls were collected from January 2012 to August 2014. Immunological parameters, including anti-aquaporin 4, antinuclear, anti-ribonucleoprotein, anti-SM, anti-SSA/Ro, anti-SSB/La and anti-ribosomal P-protein autoantibodies were examined. RESULTS: The NMOSD group exhibited a significantly higher percentage of anti-aquaporin 4 antibodies compared with the control group (76...
September 8, 2016: Neuroimmunomodulation
Maëva Lion, Alexandre Harlé, Julia Salleron, Carole Ramacci, Mario Campone, Jean-Louis Merlin
Human epidermal growth factor 2 (HER2) is overexpressed in 15-20% of breast carcinomas. The overexpression of HER2 was previously associated with a poor prognosis until the development of the first anti-HER2 therapy, trastuzumab, which drastically improves the prognosis of HER2-overexpressing breast cancers. However, its mechanism of action remains not fully understood. Several studies have proposed that the behavior and mechanism of action of trastuzumab may be drastically altered in vitro and in vivo. The present study assesses the ability of trastuzumab to inhibit the phosphorylation of the key-proteins of phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mechanistic target of rapamycin and Ras/Raf/mitogen-activated protein kinase (MAPK) signaling pathways in vitro, in breast cancer cell lines and in tumor biopsies obtained from patients treated with trastuzumab preoperative monotherapy as part of the Unicancer GEP04 RADHER phase II clinical trial...
September 2016: Oncology Letters
Lendl Tan, Danilo G Moriel, Makrina Totsika, Scott A Beatson, Mark A Schembri
Extra-intestinal pathogenic Escherichia coli (ExPEC) are responsible for diverse infections including meningitis, sepsis and urinary tract infections. The alarming rise in anti-microbial resistance amongst ExPEC complicates treatment and has highlighted the need for alternative preventive measures. SslE is a lipoprotein secreted by a dedicated type II secretion system in E. coli that was first identified as a potential vaccine candidate using reverse genetics. Although the function and protective efficacy of SslE has been studied, the molecular mechanisms that regulate SslE expression remain to be fully elucidated...
2016: PloS One
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