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Beatriz Pinto Costa, Ana Cristina Gonçalves, Ana Margarida Abrantes, Raquel Alves, Paulo Matafome, Raquel Seiça, Ana Bela Sarmento-Ribeiro, Maria Filomena Botelho, Francisco Castro-Sousa
BACKGROUND: Teduglutide is an enterotrophic analogue of glucagon-like peptide-2, with an indirect and poorly understood mechanism of action, approved for the rehabilitation of short-bowel syndrome. This study aims to analyze the response of tissue growth factors to surgical injury and teduglutide administration on an animal model of intestinal anastomosis. METHODS: Wistar rats (n = 59) were distributed into four groups: "ileal resection" or "laparotomy", each one subdivided into "postoperative teduglutide administration" or "no treatment"; and sacrificed at the third or the seventh day, with ileal sample harvesting...
January 16, 2018: Nutrición Hospitalaria: Organo Oficial de la Sociedad Española de Nutrición Parenteral y Enteral
Marjolein W J Wentink, Yvonne M Mueller, Virgil A S H Dalm, Gertjan J Driessen, P Martin van Hagen, Joris M van Montfrans, Mirjam van der Burg, Peter D Katsikis
Pathogenic gain-of-function mutations in the gene encoding phosphoinositide 3-kinase delta (PI3Kδ) cause activated PI3Kδ syndrome (APDS), a disease characterized by humoral immunodeficiency, lymphadenopathy, and an inability to control persistent viral infections including Epstein-Barr virus (EBV) and cytomegalovirus (CMV) infections. Understanding the mechanisms leading to impaired immune response is important to optimally treat APDS patients. Immunosenescence of CD8+ T cells was suggested to contribute to APDS pathogenesis...
2018: Frontiers in Immunology
M Justin Iampietro, Rafael A Larocca, Nicholas M Provine, Peter Abbink, Zi Han Kang, Christine A Bricault, Dan H Barouch
Adenovirus (Ad) vectors are being investigated as vaccine candidates, but baseline anti-vector immunity exists in human populations to both human Ad (HuAd) and chimpanzee Ad (ChAd) vectors. In this study, we investigated the immunogenicity and cross-reactivity of a panel of recently described rhesus adenoviral (RhAd) vectors. RhAd vectors elicited T cells with low exhaustion markers and robust anamnestic potential. Moreover, RhAd vector immunogenicity was unaffected by high levels of pre-existing anti-HuAd immunity...
March 21, 2018: Journal of Virology
Moslem Ahmadi, Fateme Sadri-Ardalani, Mohammad M Amiri, Mahmood Jeddi-Tehrani, Mahdi Shabani, Fazel Shokri
AIM: We investigated cellular and protective immune responses in mice vaccinated with recombinant HER2 extracellular subdomains. MATERIALS & METHODS: Balb/C mice were immunized with recombinant full HER2 extracellular domain and subdomain proteins. Humoral and cellular immune response and antitumor effect was evaluated using a syngeneic mice tumor model. RESULTS: All recombinant proteins induced secretion of IL-4 and particularly IFN-γ and IL-17 cytokines...
March 1, 2018: Immunotherapy
Marlena M Westcott, Jason Smedberg, Matthew J Jorgensen, Shelby Puckett, Douglas S Lyles
Recombinant vesicular stomatitis virus (VSV) is a promising platform for vaccine development. M51R VSV, an attenuated, M protein mutant strain, is an effective inducer of Type I interferon and dendritic cell (DC) maturation, which are desirable properties to exploit for vaccine design. We have previously evaluated M51R VSV (M51R) and M51R VSV that produces flagellin (M51R-F) as vaccine vectors using murine models, and found that flagellin enhanced DC activation and VSV-specific antibody production after low-dose vaccination...
March 19, 2018: Vaccines
Na Chen, Pei Zhu, Ting Du, Kai Han, Dang Wang, Jianfeng Ye, Shaobo Xiao, Xiaozhou Ye, Yun Wang
PURPOSE: Herein, we reported a facile strategy for synthesis of two types of modified konjac glucomannan nanoparticles (NPs). The goal of this project was to explore the potential of the NPs as vaccine adjuvants. METHODS: Firstly, anionic carboxymethylated konjac glucomannan (CKGM) and cationic quaternized konjac glucomannan (QKGM) were synthesized by chemical modification of konjac glucomannan (KGM). Subsequently, two types of NPs, CKGM/QKGM and sodium tripolyphosphate (TPP)/QKGM, were prepared through polyelectrolyte complex method and ionic cross-linking method, respectively...
March 20, 2018: Pharmaceutical Research
Cynthia Louis, Chris Burns, Ian Wicks
The pathogenesis of autoimmune diseases, such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) is driven by genetic predisposition and environmental triggers that lead to dysregulated immune responses. These include the generation of pathogenic autoantibodies and aberrant production of inflammatory cytokines. Current therapies for RA and other autoimmune diseases reduce inflammation by targeting inflammatory mediators, most of which are innate response cytokines, resulting in generalized immunosuppression...
2018: Frontiers in Immunology
Paul E Smaldino, Thomas J Flamson, Richard McElreath
Human sociality depends upon the benefits of mutual aid and extensive communication. However, diverse norms and preferences complicate mutual aid, and ambiguity in meaning hinders communication. Here we demonstrate that these two problems can work together to enhance cooperation through the strategic use of deliberately ambiguous signals: covert signaling. Covert signaling is the transmission of information that is accurately received by its intended audience but obscured when perceived by others. Such signals may allow coordination and enhanced cooperation while also avoiding the alienation or hostile reactions of individuals with different preferences...
March 20, 2018: Scientific Reports
Xiujuan Zhou, Jing Xing, Xiaoqian Tang, Wenbin Zhan
Outer membrane protein (Omp) K, OmpR and VAA have been identified with good immunogenicity from Vibrio anguillarum, and their recombinant proteins showed variable relative percent survival (RPS) in previous study. In order to develop effective bivalent vaccine candidates, recombinant (r) VAA + rOmpK (AK), rVAA + rOmpR (AR), rOmpK + rOmpR (KR) among VAA, OmpK and OmpR, or formalin-killed cells (FKC) of V. anguillarum were immunized in flounder, respectively. Results revealed that AK, AR, KR and FKC could induce the proliferation of surface membrane immunoglobulin-positive B lymphocytes or CD3+ T lymphocytes in peripheral blood lymphocytes, and significantly enhance the total antibodies, specific antibodies and immune-related gene than those of control group...
March 17, 2018: Developmental and Comparative Immunology
Himanshu Pandey, Farheen Fatma, Shivraj M Yabaji, Meera Kumari, Sarita Tripathi, Kanchan Srivastava, Dinesh K Tripathi, Surya Kant, Kishore K Srivastava, Ashish Arora
The ESAT-6 family proteins of Mycobacterium tuberculosis are regarded as the key mediators in mycobacterial virulence and are largely considered as antigens that can improve TB vaccines and diagnostics. We have characterized Rv3444c and Rv3445c proteins of the ESX-4 system of ESAT-6 family of M. tuberculosis H37Rv, and have experimentally established that these two proteins interact to form a heterodimeric complex. Complex formation resulted in induction of α-helical conformation and stability against chemical denaturation...
March 2018: Tuberculosis
Nuria González, Krisha McKee, Rebecca M Lynch, Ivelin S Georgiev, Laura Jimenez, Eulalia Grau, Eloísa Yuste, Peter D Kwong, John R Mascola, José Alcamí
BACKGROUND: Only a small fraction of HIV-1-infected patients develop broadly neutralizing antibodies (bNAbs), a process generally associated to chronic antigen stimulation. It has been described that rare aviremic HIV-1-infected patients can generate bNAbs but this issue remains controversial. To address this matter we have assessed bNAb responses in a large cohort of long-term non-progressors (LTNPs) with low or undetectable viremia. METHODS: Samples from the LTNP cohort of the Spanish AIDS Research Network (87 elite and 42 viremic controllers) and a control population of 176 viremic typical-progressors (TPs) were screened for bNAbs using Env-recombinant viruses...
2018: PloS One
Jing Wang, Mingshui Fu, Kun Liu, Ning Wang, Zhihua Zhang, Minwen Zhou, Xun Xu
PURPOSE: To quantify levels of matricellular proteins in aqueous humor samples from acute primary angle closure (APAC) and non-glaucomatous cataract eyes and investigate their correlation with intraocular pressure (IOP) fluctuation. MATERIALS AND METHODS: Aqueous humor samples were collected from 63 eyes including 29 current APAC eyes, 12 previous APAC eyes, and 22 cataract eyes. Concentrations of four main matricellular proteins (SPARC, tenascin-C, thrombospondin-2, and osteopontin) were measured using multiplexed immunoassay kits...
March 20, 2018: Current Eye Research
Anders Blomqvist, David Engblom
Fever is a common symptom of infectious and inflammatory disease. It is well-established that prostaglandin E2 is the final mediator of fever, which by binding to its EP3 receptor subtype in the preoptic hypothalamus initiates thermogenesis. Here, we review the different hypotheses on how the presence of peripherally released pyrogenic substances can be signaled to the brain to elicit fever. We conclude that there is unequivocal evidence for a humoral signaling pathway by which proinflammatory cytokines, through their binding to receptors on brain endothelial cells, evoke fever by eliciting prostaglandin E2 synthesis in these cells...
March 1, 2018: Neuroscientist: a Review Journal Bringing Neurobiology, Neurology and Psychiatry
Mirella Luciani, Tiziana Di Febo, Massimiliano Orsini, Ivanka Krasteva, Angela Cattaneo, Michele Podaliri Vulpiani, Chiara Di Pancrazio, Angela Bachi, Manuela Tittarelli
The diagnosis of dourine can be difficult because the clinical signs of this disease in horses are similar to those of surra, caused by Trypanosoma evansi . Moreover, T. equiperdum and T. evansi are closely related and, so far, they cannot be distinguished using serological tests. In a previous work, the T. equiperdum protein pattern recognized by antibodies from dourine-infected horses and the humoral immune response kinetics were investigated by immunoblotting assay; a total of 20 sera from naturally and experimentally infected horses and from healthy animals were tested...
2018: Frontiers in Veterinary Science
Francesca Macchi, José Manuel Rojas, Andrea Elizabeth Verna, Noemí Sevilla, Valentina Franceschi, Giulia Tebaldi, Sandro Cavirani, Verónica Martín, Gaetano Donofrio
Peste des Petits Ruminants Virus (PPRV) is an extremely infective morbillivirus that primarily affects goats and sheep. In underdeveloped countries where livestock are the main economical resource, PPRV causes considerable economic losses. Protective live attenuated vaccines are currently available but they induce antibody responses similar to those produced in PPRV naturally infected animals. Effective vaccines able to distinguish between vaccinated and naturally infected animals are required to PPRV control and eradication programs...
2018: Frontiers in Immunology
Xiaoyong Chen, Shasha Liu, Mohsan Ullah Goraya, Mohamed Maarouf, Shile Huang, Ji-Long Chen
Influenza A viruses (IAVs) are contagious pathogens responsible for severe respiratory infection in humans and animals worldwide. Upon detection of IAV infection, host immune system aims to defend against and clear the viral infection. Innate immune system is comprised of physical barriers (mucus and collectins), various phagocytic cells, group of cytokines, interferons (IFNs), and IFN-stimulated genes, which provide first line of defense against IAV infection. The adaptive immunity is mediated by B cells and T cells, characterized with antigen-specific memory cells, capturing and neutralizing the pathogen...
2018: Frontiers in Immunology
Marianela C Serradell, Pablo R Gargantini, Alicia Saura, Sergio R Oms, Lucía L Rupil, Luciana Berod, Tim Sparwasser, Hugo D Luján
Giardiasis is one of the most common human intestinal diseases worldwide. Several experimental animals have been used to evaluate Giardia infections, with gerbils ( Meriones unguiculatus ) being the most valuable model due to their high susceptibility to Giardia infection, abundant shedding of cysts, and pathophysiological alterations and signs of disease similar to those observed in humans. Here we report cytokine and antibody profiles both during the course of Giardia infection in gerbils and after immunization with a novel oral vaccine comprising a mixture of purified Variant-specific Surface Proteins (VSPs)...
March 19, 2018: Infection and Immunity
Hui Liu, Zhenghu Jia, Chengmao Yang, Mei Song, Zhe Jing, Yapu Zhao, Zhenzhou Wu, Liqing Zhao, Dongsheng Wei, Zhinan Yin, Zhangyong Hong
Aluminum salt (Alum) is one of the most important immune adjuvants approved for use in humans, however it is not suitable for vaccination against various chronic infectious diseases and cancers for not being able to induce cell-mediated (Th1) immunity. Here, we encapsulated an Alum colloid inside β-glucan particles (GPs), which are a type of natural particles derived from the yeast glucan shells, to prepare hybrid GP-Alum (GP-Al) adjuvant particles with a very uniform size of 2-4 μm. These hybrid particles can be used to load antigen proteins through a simple mixing procedure, and can be highly specifically targeted to antigen-presenting cells (APCs) and strongly activate dendritic cells (DCs) maturation and cytokine secretion...
March 12, 2018: Biomaterials
Alex J Krotulski, Amanda L A Mohr, Donna M Papsun, Barry K Logan
The number of emerging novel stimulants modified based on beta-keto variations of amphetamine-like substances continues to rise. Dibutylone reports described in the medical and toxicological literature are limited, therefore little information is available in terms of quantitative confirmation or metabolism. During this study, authentic human specimens, including blood, urine, vitreous humor, oral fluid and liver were quantitatively and qualitatively analyzed for the presence of dibutylone and butylone, with paired case history and demographic information...
March 15, 2018: Journal of Analytical Toxicology
Anneliese S Ashhurst, Thaigarajan Parumasivam, John Gar Yan Chan, Leon C W Lin, Manuela Flórido, Nicholas P West, Hak-Kim Chan, Warwick J Britton
Tuberculosis places a staggering burden on human health globally. The new World Health Organisation End-TB Strategy has highlighted the urgent need for more effective TB vaccines to improve control of the disease. Protein-based subunit vaccines offer potential as safe and effective generators of protective immunity, and the use of particulate vaccine formulation and delivery by the pulmonary route may enhance local immunogenicity. In this study, novel particulate subunit vaccines were developed utilising biodegradable poly(lactic-co-glycolic acid) (PLGA) slow-release particles as carriers for the Mycobacterium tuberculosis lipoprotein MPT83, together with the adjuvants trehalose-dibehenate (TDB) or Monophosphoryl lipid A (MPL)...
2018: PloS One
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