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B cell development

Francesca Micoli, Paolo Costantino, Roberto Adamo
Cell surface carbohydrates have been proven optimal targets for vaccine development. Conjugation of polysaccharides to a carrier protein triggers a T-cell dependent immune response to the glycan moiety. Licensed glycoconjugate vaccines are produced by chemical conjugation of capsular polysaccharides to prevent meningitis caused by meningococcus, pneumococcus and Haemophilus influenzae type b. However, other classes of carbohydrates (O-antigens, exopolysaccharides, wall/teichoic acids) represent attractive targets for developing vaccines...
March 14, 2018: FEMS Microbiology Reviews
Daniel M P Ardisson-Araújo, Ana Maria Rodrigues da Silva, Fernando L Melo, Ethiane Rozo Dos Santos, Daniel R Sosa-Gómez, Bergmann M Ribeiro
In this report, we described the genome of a novel baculovirus isolated from the monocot insect pest Mocis latipes , the striped grass looper. The genome has 134,272 bp in length with a G + C content of 38.3%. Based on the concatenated sequence of the 38 baculovirus core genes, we found that the virus is a betabaculovirus closely related to the noctuid-infecting betabaculoviruses including Pseudaletia unipuncta granulovirus (PsunGV), Trichoplusia ni granulovirus (TnGV), Helicoverpa armigera granulovirus (HearGV), and Xestia c-nigrum granulovirus (XecnGV)...
March 16, 2018: Viruses
Qingwang Xue, Chunxue Liu, Xia Li, Li Dai, Huaisheng Wang
Various fluorescent sensing systems for miRNAs detection have been developed. But they mostly contain enzymatic amplification reactions and label procedures. The strict reaction conditions of tool enzymes and the high cost of labeling limit their potential applications, especially in complex biological matrix. Here we have addressed the difficult problems and report a strategy for label-free fluorescent DNA dendrimers based on enzyme-free nonlinear hybridization chain reaction (HCR)-mediated multiple G-quadruplex for simple, sensitive and selective detection of miRNAs with low-background signal...
March 16, 2018: Bioconjugate Chemistry
Jacob B Williams, Clara G Buchanan, William G Pitt
Background - Patients undergoing chemotherapy can develop resistance not only to the administered drug, but also to many other unrelated types of drugs, a phenomenon known as multidrug resistance. One of the most common mechanisms of multidrug resistance is an elevated expression of drug efflux pumps. Co-delivery of an efflux pump inhibitor with a chemotherapeutic can increase the killing of multidrug resistant cancer cells. Objective - Our hypothesis was that delivering doxorubicin directly to the cytosol of multidrug resistant cancer cells via a folate-targeted liposome loaded with a perfluoropentane emulsion droplet and doxorubicin (folated eLipoDox), along with the delivery of verapamil to block the efflux pumps will prove to be more effective at killing multidrug resistant cancer cells compared to conventional drug delivery...
March 16, 2018: Pharmaceutical Nanotechnology
Lv Jiahui, Wu Jingde, He Feng, Qu Ying, Zhang Qiuqiong, Yu Chenggong
Rheumatoid Arthritis (RA) is a chronic autoimmune disease and becomes one of the major causes of disability and work force loss. The presence of abnormal B cell and autoantibodies produced by most RA patients, primarily ACPA and RF, indicate that the function of B cell was involved in the development of RA disease. Accordingly, the drug targeting B cell has become a hot spot in the treatment of RA. Studies have shown that Bruton's tyrosine kinase (BTK) is involved in the regulation of B cell proliferation and activation process...
March 16, 2018: Current Medicinal Chemistry
Xin-Peng Dun, David B Parkinson
Injury to the peripheral nervous system triggers a series of well-defined events within both neurons and the Schwann cells to allow efficient axonal regeneration, remyelination, and functional repair. The study of these events has previously been done using sections of nerve material to analyze axonal regrowth, cell migration, and immune cell infiltration following injury. This approach, however, has the obvious disadvantage that it is not possible to follow, for instance, the path of regenerating axons in three dimensions within the nerve trunk or the nerve bridge...
2018: Methods in Molecular Biology
Lyle W Murray, Iman Satti, Jodi Meyerowitz, Matthew Jones, Christian B Willberg, James E Ussher, Dominique Goedhals, Jacob Hurst, Rodney E Phillips, Helen McShane, Cloete van Vuuren, John Frater
Background: Human immunodeficiency virus (HIV)-infected individuals have a higher risk of developing active tuberculosis (TB) than HIV-uninfected individuals, but the mechanisms underpinning this are unclear. We hypothesized that depletion of specific components of Mycobacterium tuberculosis (Mtb)-specific CD4+ and CD8+ T-cell responses contributed to this increased risk. Methods: Mtb-specific T-cell responses in 147 HIV-infected and 44 HIV-uninfected control subjects in a TB-endemic setting in Bloemfontein, South Africa, were evaluated...
March 13, 2018: Journal of Infectious Diseases
Suhong Xiao, Ying-Sheng Tang, Praveen Kusumanchi, Sally P Stabler, Ying Zhang, Asok C Antony
Background: Epidemiologic and in vitro studies suggest independent linkages between poor folate and/or vitamin B-12 nutrition, genomic human papillomavirus (HPV) type 16 viral integration, and cancer. However, there is no direct evidence in vivo to support the causative role of poor folate nutrition in HPV16 integration into the cellular genome. Objective: We tested the hypothesis that folate deficiency enables the integration of HPV16 into the genome of HPV16-harboring keratinocytes, and could thereby influence earlier transformation of these cells to cancer in an animal model...
March 1, 2018: Journal of Nutrition
Caroline K Søgaard, Siver A Moestue, Morten B Rye, Jana Kim, Anala Nepal, Nina-Beate Liabakk, Siri Bachke, Tone F Bathen, Marit Otterlei, Deborah K Hill
Docetaxel is the chemotherapeutic choice for metastatic hormone-refractory prostate cancer, however, it only marginally improves the survival rate. The purpose of the present study was to examine if a peptide targeting the cellular scaffold protein PCNA could improve docetaxel's efficacy. We found that docetaxel given in combination with a cell penetrating peptide containing the AlkB homolog 2 PCNA interacting motif (APIM-peptide), reduced the prostate volume and limited prostate cancer regrowth in vivo in the immunocompetent transgenic adenocarcinoma model of prostate cancer (TRAMP)...
February 20, 2018: Oncotarget
Jing Zhu, Ying Xin, Xiaoliang Liu, Ying Wang, Ying Liu
Non-small cell lung cancer (NSCLC) accounts for ~85% of lung cancer cases worldwide. Current guidelines recommend the use of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors for patients with NSCLC. The EGF/EGFR signaling pathway has been demonstrated to activate nuclear factor (NF)-κB, which may inhibit tumor necrosis factor (TNF)-α induced cell apoptosis. The aim of the present study was to investigate whether inhibiting the EGF/EGFR signaling pathway sensitizes NSCLC cell lines to TNF-α-induced apoptosis...
April 2018: Experimental and Therapeutic Medicine
Erica J Brodie, Simona Infantino, Michael S Y Low, David M Tarlinton
Systemic lupus erythematosus (SLE) is a progressive autoimmune disease characterized by increased sensitivity to self-antigens, auto-antibody production, and systemic inflammation. B cells have been implicated in disease progression and as such represent an attractive therapeutic target. Lyn is a Src family tyrosine kinase that plays a major role in regulating signaling pathways within B cells as well as other hematopoietic cells. Its role in initiating negative signaling cascades is especially critical as exemplified by Lyn-/- mice developing an SLE-like disease with plasma cell hyperplasia, underscoring the importance of tightly regulating signaling within B cells...
2018: Frontiers in Immunology
Alexander B Rosenberg, Charles M Roco, Richard A Muscat, Anna Kuchina, Paul Sample, Zizhen Yao, Lucas Gray, David J Peeler, Sumit Mukherjee, Wei Chen, Suzie H Pun, Drew L Sellers, Bosiljka Tasic, Georg Seelig
To facilitate scalable profiling of single cells, we developed split-pool ligation-based transcriptome sequencing (SPLiT-seq), a single-cell RNA-seq (scRNA-seq) method that labels the cellular origin of RNA through combinatorial barcoding. SPLiT-seq is compatible with fixed cells or nuclei, allows efficient sample multiplexing and requires no customized equipment. We used SPLiT-seq to analyze 156,049 single-nucleus transcriptomes from postnatal day 2 and 11 mouse brains and spinal cords. Over 100 cell types were identified, with gene expression patterns corresponding to cellular function, regional specificity, and stage of differentiation...
March 15, 2018: Science
Rasa Tamosiuniene, Olga Manouvakhova, Paul Mesange, Toshie Saito, Jin Qian, Mrinmoy Sanyal, Yu-Chun Lin, Linh P Nguyen, Amir Luria, Allen B Tu, Joshua M Sante, Marlene Rabinovitch, Desmond J Fitzgerald, Brian B Graham, Aida Habtezion, Norbert F Voelkel, Laure Aurelian, Mark R Nicolls
<u>Rationale:</u> Pulmonary arterial hypertension (PH) is a life-threatening condition associated with immune dysregulation and abnormal regulatory T cell (Treg) activity, but it is currently unknown whether and how abnormal Treg function differentially affects males and females. <u>Objective:</u> To evaluate whether and how Treg-deficiency differentially affects male and female rats in experimental PH. <u>Methods and Results:</u> Male and female athymic rnu/rnu rats, lacking Tregs, were treated with the vascular endothelial growth factor receptor-2 (VEGFR2) inhibitor SU5416 or chronic hypoxia and evaluated for PH; some animals underwent Treg immune reconstitution (IR) before SU5416 administration...
March 15, 2018: Circulation Research
Weicheng Ren, Xiaofei Ye, Hong Su, Wei Li, Dongbing Liu, Mohammad Pirmoradian, Xianhuo Wang, Bo Zhang, Qiang Zhang, Longyun Chen, Man Nie, Yao Liu, Bin Meng, Huiqiang Huang, Wenqi Jiang, Yixin Zeng, Wenyu Li, Kui Wu, Yong Hou, Klas G Wiman, Zhiming Li, Huilai Zhang, Roujun Peng, Shida Zhu, Qiang Pan-Hammarström
Hepatitis B virus (HBV) infection is endemic in some parts of Asia, Africa and South America and remains to be a significant public health problem in these areas. It is known as a leading risk factor for the development of hepatocellular carcinoma, but epidemiological studies have also shown that the infection may increase the incidence of several types B-cell lymphoma. Here, by characterizing altogether 275 Chinese diffuse large B-cell lymphoma (DLBCL) patients, we showed that patients with concomitant HBV infection (surface antigen positive, HBsAg+ ) are characterized by a younger age, a more advanced disease stage at diagnosis and a reduced overall survival...
March 15, 2018: Blood
Yuna Horiuchi, Shao-Jui Lai, Azusa Yamazaki, Ayaka Nakamura, Ryunosuke Ohkawa, Kouji Yano, Takahiro Kameda, Shigeo Okubo, Shitsuko Shimano, Michio Hagihara, Shuji Tohda, Minoru Tozuka
Estimation of the function as well as the amount of high-density lipoprotein (HDL) is required to predict the risk of cardiovascular disease development. Cholesterol efflux capacity (CEC) is the key metric for determining the anti-atherosclerotic function of HDL. However, the assay methods currently used to calculate CEC are not ideal for clinical use as they require the culture of cells. In the present study, we developed a novel CEC assay using immobilized liposome-bound gel beads (ILGs), containing fluorescently labelled cholesterol, as a substitute for cultured cells...
March 15, 2018: Bioscience Reports
Aya Furusho, Hiroki Aoki, Satoko Ohno-Urabe, Michihide Nishihara, Saki Hirakata, Norifumi Nishida, Sohei Ito, Makiko Hayashi, Tsutomu Imaizumi, Shinichi Hiromatsu, Hidetoshi Akashi, Hiroyuki Tanaka, Yoshihiro Fukumoto
BACKGROUND: Abdominal aortic aneurysm (AAA) is a potentially life-threatening disease that is common in older individuals. Currently, therapeutic options are limited to surgical interventions. Although it has long been known that AAA tissue is enriched in B cells and immunoglobulins, their involvement in AAA pathogenesis remains controversial. METHODS AND RESULTS: We investigated the role of B cells and immunoglobulins in a murine model of AAA, induced with a periaortic application of CaCl2 , and in human AAA...
March 15, 2018: Journal of the American Heart Association
Aida Siyahian, Saad Ullah Malik, Adeela Mushtaq, Carol L Howe, Aneela Majeed, Tirdad Zangeneh, Samar Iftikhar, Shahid Habib, Umar Zahid, Irbaz Bin Riaz, Zabih Warraich, Warda Faridi, Faiz Anwer
Patients undergoing allogenic hematopoietic stem cell transplantation (allo-HSCT) are at a very high risk of hepatitis B virus reactivation (HBVr). Lamivudine is commonly used as prophylaxis against HBVr in high risk patients undergoing allo-HSCT. Unfortunately, its efficacy is diminishing due to the development of HBV mutant drug resistant strains. With the availability of newer antiviral agents like Entecavir, Telbivudine, Adefovir and Tenofovir, it is important to assess their role in HBVr prophylaxis. A comprehensive search of seven databases was performed to evaluate efficacy of antiviral prophylaxis against HBVr in allo-HSCT patients (PubMed/Medline, Embase, Scopus, Cochrane Library, Web of Science, CINAHL, and ClinicalTrials...
March 12, 2018: Biology of Blood and Marrow Transplantation
Xiaowen Wang, Qingyang Dong, Qian Li, Yuanyuan Li, Dianyuan Zhao, Jinjie Sun, Junliang Fu, Fanping Meng, Hu Lin, Junjie Luan, Biao Liu, Min Wang, Fusheng Wang, Fuchu He, Li Tang
BACKGROUND & AIMS: Production of neutralizing antibodies against hepatitis B surface antigen (HBsAg) is dysregulated in patients with persistent hepatitis V virus (HBV) infection. We investigated mechanisms by which this immune response to the virus is disrupted and whether it can be restored to promote clearance of HBV. METHODS: Immune-competent C57BL/6N and C57BL/6J, as well as mice deficient in follicular helper T cells (Tfh cell-deficient), B cells, or Foxp3+ T-regulatory cells (Treg cell-deficient), were given hydrodynamic injections of pAAV/HBV1...
March 12, 2018: Gastroenterology
Matthew J Atherton, Kyle B Stephenson, Jake K Nikota, Qian N Hu, Andrew Nguyen, Yonghong Wan, Brian D Lichty
Human papilloma virus (HPV)-associated cancer is a significant global health burden and despite the presence of viral transforming antigens within neoplastic cells, therapeutic vaccinations are ineffective for advanced disease. HPV positive TC1 cells are susceptible to viral oncolysis by MG1-E6E7, a custom designed oncolytic Maraba virus. Epitope mapping of mice vaccinated with MG1-E6E7 enabled the rational design of synthetic long peptide (SLP) vaccines against HPV16 and HPV18 antigens. SLPs were able to induce specific CD8+ immune responses and the magnitude of these responses significantly increased when boosted by MG1-E6E7...
March 12, 2018: Vaccine
Godwin U Ebiloma, Teresa Díaz Ayuga, Emmanuel O Balogun, Lucía Abad Gil, Anne Donachie, Marcel Kaiser, Tomás Herraiz, Daniel K Inaoka, Tomoo Shiba, Shigeharu Harada, Kiyoshi Kita, Harry P de Koning, Christophe Dardonville
African trypanosomiasis is a neglected parasitic disease that is still of great public health relevance, and a severe impediment to agriculture in endemic areas. The pathogens possess certain unique metabolic features that can be exploited for the development of new drugs. Notably, they rely on an essential, mitochondrially-localized enzyme, Trypanosome Alternative Oxidase (TAO) for their energy metabolism, which is absent in the mammalian hosts and therefore an attractive target for the design of safe drugs...
February 26, 2018: European Journal of Medicinal Chemistry
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