8,234 results
Search Results
2. Paper-based ELISA diagnosis technology for human brucellosis based on a multiepitope fusion protein
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Han Li, Hai Jiang, Mingjun Sun, Qiongqiong Bai, Dehui Yin, Jingpeng Zhang, Xiling Wu, and Jihong Shao
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Bacterial Diseases ,Serum Proteins ,B Cells ,RC955-962 ,Disease ,Pathology and Laboratory Medicine ,Biochemistry ,Epitope ,Cell Fusion ,Epitopes ,White Blood Cells ,Medical Conditions ,Filter Paper ,Animal Cells ,Zoonoses ,Arctic medicine. Tropical medicine ,Medicine and Health Sciences ,Enzyme-Linked Immunoassays ,biology ,Bacterial Pathogens ,Laboratory Equipment ,medicine.anatomical_structure ,Infectious Diseases ,Medical Microbiology ,Engineering and Technology ,Pathogens ,Cellular Types ,Public aspects of medicine ,RA1-1270 ,Bacterial Outer Membrane Proteins ,Research Article ,Neglected Tropical Diseases ,China ,Cell Physiology ,Immune Cells ,Immunology ,Equipment ,Enzyme-Linked Immunosorbent Assay ,Brucella ,Research and Analysis Methods ,Sensitivity and Specificity ,Microbiology ,Brucellosis ,Antigen ,Diagnostic Medicine ,medicine ,Humans ,Immunoassays ,Antibody-Producing Cells ,Microbial Pathogens ,B cell ,Antigens, Bacterial ,Blood Cells ,Bacteria ,business.industry ,Public Health, Environmental and Occupational Health ,Organisms ,Biology and Life Sciences ,Proteins ,Cell Biology ,medicine.disease ,biology.organism_classification ,Tropical Diseases ,Fusion protein ,Virology ,Infectious disease (medical specialty) ,Immunologic Techniques ,business - Abstract
Background Brucellosis, as a serious zoonotic infectious disease, has been recognized as a re-emerging disease in the developing countries worldwide. In china, the incidence of brucellosis is increasing each year, seriously threatening the health of humans as well as animal populations. Despite a quite number of diagnostic methods currently being used for brucellosis, innovative technologies are still needed for its rapid and accurate diagnosis, especially in area where traditional diagnostic is unavailable. Methodology/Principal findings In this study, a total of 22 B cell linear epitopes were predicted from five Brucella outer membrane proteins (OMPs) using an immunoinformatic approach. These epitopes were then chemically synthesized, and with the method of indirect ELISA (iELISA), each of them displayed a certain degree of capability in identifying human brucellosis positive sera. Subsequently, a fusion protein consisting of the 22 predicted epitopes was prokaryotically expressed and used as diagnostic antigen in a newly established brucellosis testing method, nano-ZnO modified paper-based ELISA (nano-p-ELISA). According to the verifying test using a collection of sera collected from brucellosis and non-brucellosis patients, the sensitivity and specificity of multiepitope based nano-p-ELISA were 92.38% and 98.35% respectively. The positive predictive value was 98.26% and the negative predictive value was 91.67%. The multiepitope based fusion protein also displayed significantly higher specificity than Brucella lipopolysaccharide (LPS) antigen. Conclusions B cell epitopes are important candidates for serologically testing brucellosis. Multiepitope fusion protein based nano-p-ELISA displayed significantly sensitivity and specificity compared to Brucella LPS antigen. The strategy applied in this study will be helpful to develop rapid and accurate diagnostic method for brucellosis in human as well as animal populations., Author summary Brucellosis is one of the most important zoonosis in the world and has caused tremendous economic losses in agriculture and animal husbandry in many countries. Developing rapid, sensitive and specific diagnostic methods is very important for early detection and treatment of brucellosis patients. In this study, a novel diagnostic technique, nano-ZnO modified paper ELISA, was established. The antigen used in this technique was a fusion protein containing multiple B cell epitopes, which were predicted from Brucella major outer membrane proteins such as Bp26, Omp31, Omp16, Omp2b and Omp25. Comparing to traditional LPS antigen, this multiepitope based antigen displayed considerably higher sensitivity and higher specificity in laboratory. With the strategy described in this paper, more efficient epitopes and protein antigen can be identified in the future. Currently, LPS antigen is only prepared from live Brucella, while protein antigen can be produced in large quantities in prokaryotic expression system. In addition to nano-p-ELISA, this protein antigen can also be used for development other methods such as fluorescent polarization assay (FPA) and immunochromatographic assay (ICA) to meet the varied demand for brucellosis testing.
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- 2021
3. Dynavax Announces Publication of Two Papers in Leading Oncology Journal Highlighting Data From Clinical Studies of Its TLR9 Agonist, SD-101
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Dynavax Technologies Corp. ,Medical research ,Medicine, Experimental ,Non-Hodgkin's lymphomas ,B cells ,Clinical trials ,Melanoma ,Periodical publishing ,Pharmaceutical industry ,Banking, finance and accounting industries ,Business - Abstract
BERKELEY, Calif., Aug 28, 2018 (GLOBE NEWSWIRE via COMTEX) -- Dynavax Technologies Corporation (NASDAQ: DVAX) today announced that two peer-reviewed papers reporting clinical studies of SD-101 have been published by [...]
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- 2018
4. Prolymphocytic leukaemia of B- and T-cell subtype: a state-of-the-art paper.
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Dungarwalla, M., Matutes, E., and Dearden, C. E.
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LYMPHOCYTIC leukemia , *T cells , *B cells , *IMMUNOPHENOTYPING , *HUMAN cytogenetics , *CYTOLOGY , *PROGNOSIS - Abstract
Prolymphocytic leukaemias of B and T cell subtype are rare diseases. Despite recent advances in immunophenotyping and molecular cytogenetics, leading to a better understanding of the underlying cell biology of the prolymphocytic leukaemias, prognosis for these patients remains poor. Purine analogues and monoclonal antibodies have shown efficacy in B-cell prolymphocytic leukaemia although further studies are warranted. Monoclonal antibody therapy with alemtuzumab has significantly improved outcome in T-cell prolymphocytic leukaemia (T-PLL) but responses are still transient and further disease progression is inevitable. While allogeneic stem cell transplant is an attractive option, due to the older age group of T-PLL patients the morbidity and mortality associated with the procedure is significant. [ABSTRACT FROM AUTHOR]
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- 2008
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5. research paper CD21S antigen expression in tumour cells of diffuse large B-cell lymphomas is an independent prognostic factor indicating better overall survival.
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Ogawa, Shoko, Yamaguchi, Motoko, Oka, Kouji, Taniguchi, Masanori, Ito, Motohiro, Nishii, Kazuhiro, Nakase, Kazunori, Ohno, Toshiyuki, Kita, Kenkichi, Kobayashi, Tohru, and Shiku, Hiroshi
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CD antigens , *B cell lymphoma , *CANCER cells , *IMMUNOPHENOTYPING , *IMMUNOHISTOCHEMISTRY techniques , *ONCOLOGY - Abstract
To evaluate the clinical significance of CD21S expression of diffuse large B-cell lymphoma (DLBCL) tumour cells, we compared their clinical features, immunophenotype, response to therapy and outcome in relation to CD21S expression. Between 1987 and 1999, frozen sections from 240 DLBCL cases were examined for CD21S expression by immunohistochemical methods. CD21S expression was detected on the tumour cells of 87 (36%) cases. The median age of the CD21S+ DLBCL cases was 65 years (range: 17–84 years), the male–female ratio was 42:45, and they showed the following clinical features: Eastern Cooperative Oncology Group score >1 in 14%, lactate dehydrogenase greater than normal levels in 38%, extranodal sites >1 in 14%, stages III/IV disease at diagnosis in 29%, B symptoms in 17%, and a high/high–intermediate International Prognostic Index (IPI) in 23%. They also showed a better overall survival ( P = 0·00001, log-rank test) and a better complete remission rate ( P = 0·00004, chi-square test) than CD21S− DLBCL. Moreover, CD21S+ DLBCL showed a better survival than CD21S− DLBCL for both low/low–intermediate and high/high–intermediate risk categories of IPI ( P = 0·045 and P = 0·0016 respectively). Multivariate analysis identified CD21S expression as an independent factor for survival when compared with the five IPI factors. These findings indicate that CD21S expression of DLBCL tumour cells is a useful prognostic factor for survival. [ABSTRACT FROM AUTHOR]
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- 2004
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6. research paper Expression of cyclin E in resting and activated B-chronic lymphocytic leukaemia cells: cyclin E/cdk2 as a potential therapeutic target.
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Decker, Thomas, Hipp, Susanne, Hahntow, Ines, Schneller, Folker, and Peschel, Christian
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LYMPHOCYTIC leukemia , *CYCLIN-dependent kinases , *B cells , *LEUKEMIA , *CELL proliferation , *CELL death - Abstract
Disease progression in B-cell chronic lymphocytic leukaemia (B-CLL) is determined by the interplay between proliferation kinetics in the proliferating compartment and cell death in the accumulating compartment. Improving our knowledge of cell cycle regulation in B-CLL cells might therefore be important for identifying therapeutic targets. Cyclin E was detected by Western blotting in purified B-CLL cells from peripheral blood samples of all 12 patient tested but not in normal peripheral blood B cells. While cyclin-dependent kinase 2 (cdk2) expression was similar in different samples, p27 and cyclin E expression was highly variable. We further investigated the regulation of p27, cyclin E and cdk2 in an in vitro model of cycling B-CLL cells. Cyclin E and cdk2 expression was increased in B-CLL cells stimulated with a CpG-oligodeoxynucleotide and interleukin-2, while p27 expression rapidly declined. This was accompanied by the increased formation of cyclin E–cdk2 complexes, which were able to phosphorylate Histone H1 in vitro. Pharmacological inhibition of cdk2 activity with Roscovitine-inhibited thymidine incorporation and Histone H1 phosphorylation. We conclude that further evaluation of cyclin E and p27 in peripheral blood cells might help to identify prognostic subgroups. In addition, inhibition of Cyclin E–cdk2 activity by Roscovitine might be a new therapeutic strategy in B-CLL. [ABSTRACT FROM AUTHOR]
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- 2004
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7. research paper Overexpression of the Ikaros 6 isoform is restricted to t(4;11) acute lymphoblastic leukaemia in children and infants and has a role in B-cell survival.
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Ruiz, Anna, Jie Jiang, Kempski, Helena, and Brady, Hugh J.M.
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TRANSCRIPTION factors , *MYELOID leukemia , *GENES , *DNA , *B cells , *CHILDREN - Abstract
The Ikaros transcription factor has been shown to play an important role in the differentiation of both myeloid and lymphoid lineages. Mice heterozygous for a dominant negative (DN) ikaros isoform develop T-cell leukaemia and lymphoma with 100% penetrance. Overexpression of DN Ikaros isoforms has been reported in some forms of leukaemia, such as childhood acute myelomonocytic and monocytic leukaemias, adult B-cell acute lymphoblastic leukaemias (B ALL) and in childhood and adult pre-B ALL. In this study, the expression of Ikaros isoforms in 49 infant and childhood leukaemia patients was analysed by reverse transcription polymerase chain reaction and Western blot analysis. We found overexpression of the DN Ikaros 6 (Ik6) isoform in a subset of leukaemia patients harbouring t(4;11) translocations. To further study the consequences of Ik6 overexpression in B ALL, we inducibly expressed Ik6 in BaF3 cells and found that Ik6 overexpression delayed cell death after interleukin-3 withdrawal, suggesting that overexpression of Ik6 found in t(4;11) B cells could contribute to leukaemogenesis by preventing the apoptosis of cells in an environment with reduced survival factors. [ABSTRACT FROM AUTHOR]
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- 2004
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8. research paper Single nucleotide polymorphisms of the inflammatory cytokine genes in adults with chronic immune thrombocytopenic purpura.
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Satoh, Takashi, Pandey, Janardan P., Okazaki, Yuka, Yasuoka, Hidekata, Kawakami, Yutaka, Ikeda, Yasuo, and Kuwana, Masataka
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AUTOIMMUNE diseases , *CYTOKINES , *NUCLEOTIDES , *GLYCOPROTEINS , *IMMUNOGLOBULINS , *B cells - Abstract
Single nucleotide polymorphisms (SNPs) of inflammatory cytokine genes were examined in 84 adult Japanese patients with chronic immune thrombocytopenic purpura (ITP) and 56 race-matched healthy controls. The SNPs examined were within the genes encoding tumour necrosis factor (TNF)- α (−238 G/A and −308 G/A), TNF- β (+252 G/A), and interleukin (IL)-1 β (−511 C/T and +3953 T/C). Of these SNPs, the frequency of the TNF- β (+252) G/G phenotype was significantly higher in ITP patients than in healthy controls (21% vs. 7%, P = 0·04, odds ratio = 3·6, 95% confidence interval 1·1–11·1), while no significant association was detected for the other SNPs. The distribution of the TNF- β (+252) phenotype was not associated with human leucocyte antigen class II alleles or the therapeutic response in ITP patients. The frequency of circulating anti-glycoprotein IIb/IIIa antibody-producing B cells was significantly higher in ITP patients with the TNF- β (+252) G/G phenotype than in those with the G/A or A/A phenotype (11·9 ± 4·9 vs. 6·8 ± 4·9 and 3·7 ± 2·8 per 105 peripheral blood mononuclear cells; P = 0·02 and P < 0·001, respectively). These findings suggest that the SNP located at TNF- β (+252) contributes to susceptibility to chronic ITP by controlling the autoreactive B-cell responses to platelet membrane glycoproteins. [ABSTRACT FROM AUTHOR]
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- 2004
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9. research paper Impairment of death-inducing signalling complex formation in CD95-resistant human primary lymphoma B cells.
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Lajmanovich, Alicia, Irisarri, Magdalena, Molens, Jean-Paul, Pasquier, Marie-Anne, Sotto, Jean-Jacques, Bensa, Jean-Claude, Leroux, Dominique, and Plumas, Joël
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CELLULAR signal transduction , *LYMPHOMAS , *CELL death , *B cells , *INTERLEUKIN-1 , *LYMPHOCYTES - Abstract
Multiple mechanisms exist by which tumour cells can escape CD95-mediated apoptosis. Previous studies by our laboratory have shown that primary B cells from non-Hodgkin's Lymphoma (B-NHL) were resistant to CD95-induced cell death. In the current study, we have analysed the mechanisms underlying CD95 resistance in primary human lymphoma B cells. We report that FADD (FAS-associated death domain protein) and caspase-8 were constitutively expressed in lymphoma B cells and that the CD95 pathway was blocked upstream to caspase-8 activation. However, caspase-8 was processed and functional after treatment with staurosporine (STS). We found that the expression levels of FLICE (FADD-like interleukin-1 beta-converting enzyme)-Inhibitory Protein (c-FLIP) and Bcl-2-related proteins were heterogeneous in B-NHL cells and were not related to CD95 resistance. Finally, we report the absence of a CD95-induced signalling complex [death-inducing signalling complex (DISC)] in lymphoma B cells, with no FADD and caspase-8 recruitment to CD95 receptor. In contrast, DISC formation was observed in CD95-resistant non-tumoural (NT) B cells. Therefore, we propose that the absence of DISC formation in primary lymphoma B cells may contribute to protect these cells from CD95-induced apoptosis. [ABSTRACT FROM AUTHOR]
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- 2004
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10. research paper Fludarabine, mitoxantrone and dexamethasone in the treatment of indolent B- and T-cell lymphoid malignancies in Chinese patients.
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Ma, Shing Y., Au, Wing Y., Chim, Chor S., Lie, Albert K. W., Lam, Clarence C. K., Tse, Eric, Leung, Anskar Y. H., Liang, Raymond, and Kwong, Yok L.
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LYMPHOCYTIC leukemia , *LEUKEMIA diagnosis , *FLUDARABINE , *B cells , *T cells , *LYMPHOMAS , *CHINESE people , *LEUKEMIA treatment - Abstract
The treatment results of indolent lymphoid malignancies in Chinese are poorly reported. The efficacy of FND (fludarabine 25 mg/m2/d, ×3; mitoxantrone 10 mg/m2/d, ×1; dexamethasone 20 mg/d, ×5; monthly cycles, ×6) in 95 Chinese patients with indolent B-cell malignancies (at diagnosis: 55, relapse/refractory disease: 40) and nine Chinese patients with T-cell large granular lymphocyte leukaemia (T-LGL leukaemia) (at diagnosis: two, refractory disease: seven) was evaluated. For B-cell malignancies, the complete response (CR), partial response (PR) and overall response (OR) rates were 50·5%, 18% and 68·5% respectively. Better results were obtained for primary versus relapse/refractory disease (CR: 60% vs. 37·5%, P = 0·03; OR: 84% vs. 47·5%, P < 0·001; median progression-free survival (PFS): 44 months vs. 22 months; 2-year PFS: 66% vs. 47%, P = 0·039; overall survival (OS): not reached vs. 32%; 2-year OS: 92% vs. 58%, P < 0·001). Responsive patients (CR/PR) had a better median PFS (44 months vs. 5 months, P < 0·001) and OS (67 months vs. 13 months, P < 0·001) than unresponsive patients. For T-LGL leukaemia, the CR and molecular-remission rates were 56% and 67% (median follow-up: 23 months). FND is an active regimen for the treatment of indolent B- and T-cell malignancies in Chinese patients, with results comparable with Western patients with similar indolent lymphomas. [ABSTRACT FROM AUTHOR]
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- 2004
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11. research paper Clinical follow-up indicates differential accuracy of magnetic resonance imaging and immunocytology of the cerebral spinal fluid for the diagnosis of neoplastic meningitis – a single centre experience.
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Zeiser, Robert, Burger, Jan A., Biey, Thorsten A., Windfuhr-Blum, Marissa, Schulte-Monting, Jürgen, and Behringer, Dirk M.
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NEISSERIA meningitidis , *CEREBROSPINAL fluid , *MAGNETIC resonance imaging , *TUMORS , *SPINAL cord , *B cells - Abstract
In patients with neoplastic meningitis (NM), the rapid institution of intrathecal therapy may ameliorate the course of disease, indicating that a timely diagnosis is clinically relevant. As immunocytology (IC) of cerebrospinal fluid and magnetic resonance imaging (MRI), as diagnostic methods, have potential pitfalls, the present study assessed the results of both methods, to determine the predictive capability of the initial evaluations with respect to the risk that the patient would develop NM during the course of their disease. A total of 166 individuals with B-cell non-Hodgkin's lymphoma (B-NHL; n = 95), B-acute lymphocytic leukaemia (ALL; n = 18), acute myeloid leukaemia ( n = 27) or solid tumours ( n = 26), with at least one definitive IC and MRI result within 3 weeks, were evaluated at a median follow-up of 29·5 months (range 6–53 months). IC and MRI results reached the highest concordance (98%) in B-NHL patients and were most discordant in ALL patients (43%). In haematological malignancies, IC displayed considerable sensitivity, ranging from 89% to 95%, while MRI had very low sensitivity. Conversely, MRI showed high sensitivity (100%) and specificity (92%) in solid tumours. We conclude that IC is of particular value in the diagnosis of NM due to haematological malignancies while MRI is superior to IC in the diagnosis of NM due to solid tumours. [ABSTRACT FROM AUTHOR]
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- 2004
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12. research paper Preclinical studies of fibroblast growth factor receptor 3 as a therapeutic target in multiple myeloma.
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Peterson, Joshua L., Zhihua Li, Xiao-Yan Wen, Joshua L., Masih-Khan, Esther, Hong Chang, Pollett, Jonathan B., Trudel, Suzanne, and Stewart, A. Keith
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FIBROBLAST growth factors , *THERAPEUTICS , *MULTIPLE myeloma , *PROTEIN-tyrosine kinases , *B cells , *HEMATOLOGY - Abstract
Dysregulation of fibroblast growth factor receptor 3 ( FGFR3) by the translocation t(4;14)(p16;q32) occurs in 15% of multiple myeloma (MM) patients and confers a growth and survival advantage to malignant plasma cells. As FGFR3 is a molecular target, we assessed the therapeutic potential of the FGFR-specific tyrosine kinase inhibitors SU5402 and SU10991 in MM. SU5402 inhibited FGFR3 phosphorylation in vitro and in murine MM tumour models. B cells dependent on FGFR3 for survival were specifically sensitive to SU5402. A panel of 11 human myeloma cell lines was studied, five bearing the t(4;14) translocation. The KMS11 human myeloma cell line, which expresses constitutively active mutant FGFR3, displayed an 85% decrease in S-phase cells, a 95% increase in G0/G1 cells, and 4·5-fold increase in apoptotic cells after 72 h treatment with 10 μmol/l SU5402. Activated extracellular signal-regulated kinases 1 and 2 and signal transducer and activator of transcription 3 were rapidly down-regulated after SU5402 treatment. In human myeloma cell lines expressing wild-type FGFR3 the stimulating effect of aFGF ligand was abrogated by SU5402 treatment. Myeloma cells lacking the t(4;14) or with the t(4;14) and a secondary RAS mutation did not respond to therapy. These findings support the development of clinical trials of early intervention with FGFR3 inhibitors in t(4;14) myeloma. [ABSTRACT FROM AUTHOR]
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- 2004
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13. research paper Incidence of novel N-glycosylation sites in the B-cell receptor of lymphomas associated with immunodeficiency.
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Forconi, Francesco, Capello, Daniela, Berra, Eva, Rossi, Davide, Gloghini, Annunziata, Cerri, Michaela, Muti, Giuliana, Morra, Enrica, Paulli, Marco, Magrini, Umberto, Lucioni, Marco, Rambaldi, Alessandro, Lauria, Francesco, Carbone, Antonio, Stevenson, Freda K., and Gaidano, Gianluca
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GLYCOSYLATION , *B cells , *LYMPHOMAS , *IMMUNODEFICIENCY , *ANTIBODY diversity , *HEMATOLOGY - Abstract
Novel N-glycosylation sites are introduced by somatic mutation into the V genes of the majority of follicular lymphomas. Sites are positively selected and rare in normal memory B cells, indicating a potential role in tumour survival in the germinal centre (GC). The incidence of c. 40% in diffuse large B-cell lymphomas (DLBCL) parallels the known heterogenity of the disease. Immunodeficiency-related non-Hodgkin's lymphomas (NHL) include post-transplant lymphoproliferative disorders (PTLD) and acquired immunodeficiency syndrome-related NHL (AIDS-NHL). Most PTLD derive from B cells that carry mutated VH genes and that have completed the GC reaction. All AIDS-NHL carry mutated VH genes and variable features of GC or post-GC cells. To determine if N-glycosylation is a feature of immunodeficiency-related lymphomas, we analysed the VH genes of 19 PTLD and 36 AIDS-NHL. Novel sites were rare in PTLD (4/19), similar to memory B cells ( P = 0·15). AIDS-NHL, including DLBCL and Burkitt's lymphomas (BL), showed heterogeneity with 16 of 36 (44%) having novel sites. The findings indicate no selection of N-glycosylation sites in PTLD, consistent with post-GC features. The variable incidence of N-glycosylation sites in AIDS-NHL mirrors that in DLBCL and sporadic BL of immunocompetent hosts, supporting the known heterogeneity of these disorders, and possibly pointing to distinct routes of tumour development. [ABSTRACT FROM AUTHOR]
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- 2004
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14. research paper Biological diagnosis of primary intraocular lymphoma.
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Merle-Béral, Hélène, Davi, Frédéric, Cassoux, Nathalie, Baudet, Sylvie, Colin, Chantal, Gourdet, Thomas, Bodaghi, Bahram, and LeHoang, Phuc
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LYMPHOMAS , *CYTOLOGY , *INTERLEUKIN-10 , *B cells , *POLYMERASE chain reaction , *T cells - Abstract
Primary intraocular lymphoma (PIOL) is a rare presentation of lymphoma that is particularly difficult to recognize. In our institution, 36 cases of PIOL were diagnosed between March 1997 and July 2002. The recognition of lymphoma cells by cytology with or without immunophenotyping on slides generated a strong suspicion of the diagnosis in 34 of 36 cases. The diagnosis was confirmed by measurement of interleukin-10 (IL-10) in the vitreous humour or aqueous humour; high levels were observed in 35 of 36 cases, all were of B-cell origin. As expected, the only case with T-cell lymphoma had a very low level of IL-10. Furthermore, IL-10 levels excluded this diagnosis in two cases that were incorrectly suspected of PIOL after cytological examination. Finally, detection of clonality by polymerase chain reaction techniques, performed in 29 cases, represented a helpful tool in diagnosing PIOL as this approach definitively confirmed the diagnosis of B- or T-cell lymphoma in 17 cases. [ABSTRACT FROM AUTHOR]
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- 2004
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15. research paper Intracellular signalling molecules as immunohistochemical markers of normal and neoplastic human leucocytes in routine biopsy samples.
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Pozzobon, Michela, Marafioti, Teresa, Hansmann, Martin-Leo, Natkunam, Yasodha, and Mason, David Y.
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LEUCOCYTES , *IMMUNOHISTOCHEMISTRY , *BIOPSY , *PHOSPHOLIPASES , *MOLECULES , *IMMUNOGLOBULINS , *LYMPHOCYTES - Abstract
We have investigated whether intracellular signal transduction molecules can be used as immunohistological markers of normal and neoplastic human leucocytes in routine tissue sections. We obtained selective labelling of white cells for eight such molecules (the ‘linker’ molecules SLP-76 and BLNK, the Src family kinases Lyn, Fyn, Syk and Hck, and the phospholipases PLC- γ1 and PLC- γ2). Antibodies to SLP-76 and PLC- γ1 selectively labelled T cells, and antibodies to BLNK, Lyn, Fyn, Syk and PLC- γ2 labelled B cells (although Fyn immunostaining was restricted to mantle zone B cells). Antibodies to the Syk and Hck kinases labelled probable thymocyte precursors at the periphery of the thymic cortex. In addition to lymphoid cells, several other leucocyte types were immunostained (e.g. SLP-76, Lyn, Syk and Hck were found in megakaryocytes, myeloid cells and/or macrophages, and PLC- γ2 was detected in arterial endothelium). SLP-76 and PLC- γ1 were found in most T-cell lymphomas studied, and some B-cell lymphomas were also positive for PLC- γ1 (e.g. diffuse large cell and Burkitt's lymphoma). The five B cell-associated markers were found in most B-cell non-Hodgkin's lymphomas, although some diffuse large B-cell lymphomas were negative (e.g. for Lyn) and anti-Fyn tended not to stain small B-cell neoplasms. The observation that a range of leucocyte signalling molecules can be detected in routine biopsies offers new possibilities for studying normal and neoplastic human white cells in diagnostic tissue samples. [ABSTRACT FROM AUTHOR]
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- 2004
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16. research paper Long-acting β2-adrenergic formoterol and salmeterol induce the apoptosis of B-chronic lymphocytic Leukaemia cells.
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Mamani-Matsuda, Maria, Moynet, Daniel, Molimard, Mathieu, Ferry-Dumazet, Hélène, Marit, Gérald, Reiffers, Josy, and Mossalayi, M. Diavad
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ADENOSINE monophosphate , *LEUKEMIA , *B cells , *LYMPHOCYTIC leukemia , *BLOOD diseases , *HEMATOLOGY - Abstract
B-cell chronic lymphocytic leukaemia (B-CLL) is a neoplastic disorder characterized by defective apoptosis, cell accumulation in G0/G1, and high expression of BCL2 oncogene. Intracellular cyclic adenosine monophosphate (cAMP) accumulation increases the chemosensitivity of B-CLL cells in vitro and in vivo. In the present study, we investigated the effects of β2-adrenergic compounds, well known cAMP-inducing drugs, on the in vitro survival of leukaemia cells. In contrast to the short-acting β2-mimetic (β2Mim) salbutamol, a consistent pro-apoptotic effect was observed with the long-acting β2Mim salmeterol and formoterol. Normal B cells isolated from control donors were totally resistant to the above molecules. These compounds also increased chlorambucil- and fludarabine-induced death of B-CLL cells. Blockade of β-adrenergic receptor signalling or cAMP did not alter B-CLL apoptosis with β2 Mimagents. Leukaemia cell apoptosis by β2Mim correlated with an increase in calcium influx, decreased bcl-2 protein and mRNA levels, increase in BAX gene expression and a marked rise in BCL2/BAX mRNA ratios. Interleukin-4, a cytokine that increases bcl-2 expression in B-CLL cells, rescued leukaemia cell from apoptosis with β2Mim. These data show that long-acting β2-adrenergic agents promote apoptotic leukaemia cell death through an adrenoreceptor- and cAMP-independent, Ca2+-dependent mechanism. [ABSTRACT FROM AUTHOR]
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- 2004
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17. ORIGINAL PAPER Frequency analysis of B lymphocytes specific for Rh antigens in naturally immunized Rh-negative women.
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Pasha, R. P. K., Shokrgozar, M. A., Bahrami, Z. S., and Shokri, F.
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B cells , *LYMPHOCYTES , *ANTIGENS , *PARTURITION , *ERYTHROBLASTOSIS fetalis , *HEMOLYTIC anemia - Abstract
Despite a successful outcome of the anti-D prophylaxis programme, alloimmunization still occurs. The aim of this study was to estimate the frequency of Rh-specific B lymphocytes in the peripheral blood of nine Rh-alloimmunized individuals at different time intervals after parturition. The donors’ B lymphocytes were transformed with Epstein–Barr virus (EBV) and cultured at different cell densities over a feeder of human fetal fibroblasts. Culture supernatants were screened for human immunoglobulin by enzyme-linked immunosorbent assay (ELISA) and for anti-Rh antibody by using a direct haemagglutination technique. The percentage of CD19+ B lymphocytes in peripheral blood was determined by flow cytometry, and the frequency of Rh-specific B lymphocytes was estimated by limiting-dilution assay (LDA). The frequency of Rh-specific B lymphocytes varied from 1 : 150 to 1 : 27 850 in different donors. There was a decrease in this frequency and level of anti-Rh antibody with increase in time interval between bleeding and last exposure to the antigen. Furthermore, a positive correlation was observed between the titre of Rh-specific antibody and frequency of Rh-specific B cells in each of three subjects bled at multiple time-points postdelivery. The magnitude of the specific antibody response to Rh antigens varies greatly in Rh-alloimmunized women, which partly reflects the difference in frequency of specific B cells in these individuals. [ABSTRACT FROM AUTHOR]
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- 2004
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18. Inhibition of CD1d activation suppresses septic mortality: a role for NK-T cells in septic immune dysfunction1 <FN ID="FN1"><NO>1</NO>This paper was presented at the 35th annual meeting of the Association for Academic Surgery, November 9, 2002, Boston, MA.</FN>
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Rhee, Rebecca J., Carlton, Stacey, Lomas, Joanne L., Lane, Crystal, Brossay, Laurent, Cioffi, William G., and Ayala, Alfred
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IMMUNOLOGIC diseases , *T cells , *B cells , *PHAGOCYTES - Abstract
Background.Studies indicate that following septic insult there is development of generalized immune dysfunction in T cells, B cells and phagocytes, which is thought to contribute to morbidity and mortality. Specifically, there is a shift in the lymphocytes of septic animals toward an increased release of Th2 cytokines. NK-T cells have been shown to contribute to propagation of the Th2 response. The influence of NK-T cells on the immune response to septic challenge is poorly understood. In this study, we examine whether NK-T cells contribute to the immune dysfunction seen following the onset of polymicrobial sepsis, as produced by cecal ligation and puncture (CLP).Materials and methods.Male 129S1/SvImJ mice were pretreated with either rat IgG (isotypic control) or monoclonal antibody to CD1d (clone 1B1) (0.5 mg), which blocks signaling/antigen presentation via the CD1d cell surface receptor, thereby, ablating the activation and differentiation of the NK-T cells. Septic survival with and without anti-CD1d (CLP/CD1d) pretreatment was assessed. Mice sacrificed 24 h after CLP were assessed for change in splenic %NK-T cell (via flourescense activated cell sector) and for splenic, hepatic, and lymphoid/macrophage production of pro-inflammatory or anti-inflammatory cytokines (via enzyme-linked immunosorbent assay).Results.Administration of anti-CD1d reduced septic mortality 35% at 6–10 d (n = 23 mice/group) (P < .05). There was a consistent increase in the %CD3+ NK1.1+ cell population (NK-T cells) in septic mice (1.706%), which was markedly suppressed by pretreatment with anti-CD1d (0.592%). IL-6 and IL-10 levels were suppressed by anti-CD1d in the spleen and blood.Conclusions.Together these findings imply not only that NK-T cells may play a role in mediating the immune suppression seen in bacterial sepsis, but that inhibition of their activation promotes survival to septic challenge. [Copyright &y& Elsevier]
- Published
- 2003
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19. Position paper on the therapeutic use of rituximab in CD20-positive diffuse large B-cell non-Hodgkin's lymphoma.
- Author
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Pettengell, Ruth and Linch, David
- Subjects
- *
RITUXIMAB , *DRUG therapy , *B cells - Abstract
Summary. The available data on rituximab in combination with chemotherapy confirm that the addition of an independently active biological agent to full-dose standard chemotherapy results in higher rates of complete response, lower rates of relapse, prolonged survival, little additional toxicity and no compromise of the dose intensity of standard chemotherapy regardless of age and risk group. Given the strength of these data, the British Committee for Standards in Haematology believes that rituximab should be available for prescription by UK haematologists and oncologists according to its licensed indication in patients with diffuse large B-cell lymphoma until further data are available to confirm or refute these results. We consider that the use of rituximab with chemotherapy in aggressive lymphoma is cost-effective and that failure to support its introduction will be strongly in conflict with professional and patient opinion. [ABSTRACT FROM AUTHOR]
- Published
- 2003
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20. Correction: Suleman et al. Immunoinformatics and Immunogenetics-Based Design of Immunogenic Peptides Vaccine against the Emerging Tick-Borne Encephalitis Virus (TBEV) and Its Validation through In Silico Cloning and Immune Simulation. Vaccines 2021, 9 , 1210
- Author
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Suleman, Muhammad, Tahir ul Qamar, Muhammad, Kiran, Rasool, Samreen, Rasool, Aneela, Albutti, Aqel, Alsowayeh, Noorah, Alwashmi, Ameen S. S., Aljasir, Mohammad Abdullah, Ahmad, Sajjad, Hussain, Zahid, Rizwan, Muhammad, Ali, Syed Shujait, Khan, Abbas, and Wei, Dong-Qing
- Subjects
TICK-borne encephalitis viruses ,B cells ,MOLECULAR docking ,DYNAMIC simulation ,IMMUNE response - Abstract
This correction notice addresses an error in a published paper titled "Immunoinformatics and Immunogenetics-Based Design of Immunogenic Peptides Vaccine against the Emerging Tick-Borne Encephalitis Virus (TBEV) and Its Validation through In Silico Cloning and Immune Simulation." The authors discovered that the abstract of the paper was an exact duplicate of the abstract from a previously published paper by the same authors. This mistake occurred due to a wrong version being mistakenly uploaded during the publication process. The corrected abstract provides information about the design of a potential antigenic and non-allergenic multi-epitope subunit vaccine against TBEV, which shows promise for both in vitro and in vivo analyses. The authors state that this error does not affect the scientific conclusions of the paper. [Extracted from the article]
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- 2024
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21. Correction: Chakraborty et al. Bromelain a Potential Bioactive Compound: A Comprehensive Overview from a Pharmacological Perspective. Life 2021, 11 , 317.
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Chakraborty, Arka Jyoti, Mitra, Saikat, Tallei, Trina E., Tareq, Abu Montakim, Nainu, Firzan, Cicia, Donatella, Dhama, Kuldeep, Emran, Talha Bin, Simal-Gandara, Jesus, and Capasso, Raffaele
- Subjects
BROMELIN ,B cells ,BIOACTIVE compounds ,OVALBUMINS ,BERBERINE ,REPERFUSION ,APIS cerana - Abstract
This document is a correction notice for a paper on the potential bioactive compound bromelain. The authors have identified errors in one section of the paper and provide revised references. The corrected table includes therapeutic studies of bromelain based on experimental studies. The document also includes a compilation of various scientific studies and articles related to the use of bromelain for various medical purposes. The studies explore the potential benefits of bromelain in treating conditions such as cancer, inflammation, thrombosis, and pain. The document provides a comprehensive overview of the scientific research on bromelain and its potential applications in medicine. [Extracted from the article]
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- 2024
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22. Enhanced mitochondrial function in B cells from elderly type-2 diabetes mellitus patients supports intrinsic inflammation.
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Frasca, Daniela and Bueno, Valquiria
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MITOCHONDRIAL physiology ,IN vitro studies ,FLOW cytometry ,PEARSON correlation (Statistics) ,RESEARCH funding ,BODY mass index ,ACADEMIC medical centers ,T-test (Statistics) ,INFLUENZA vaccines ,VACCINE effectiveness ,POLYMERASE chain reaction ,ENZYME-linked immunosorbent assay ,AGE distribution ,DESCRIPTIVE statistics ,HEMAGGLUTINATION tests ,METABOLITES ,MESSENGER RNA ,TYPE 2 diabetes ,AMYLOID ,STATISTICS ,INFLAMMATION ,CYTOKINES ,FACTOR analysis ,DATA analysis software ,B cells ,OBESITY ,C-reactive protein ,TUMOR necrosis factors ,INTERLEUKINS ,BIOMARKERS - Abstract
In this paper, we measured B cell function in elderly healthy individuals (E
H ) and in elderly patients with Type-2 Diabetes Mellitus (T2DM, ET2DM ), which are treatment-naive, as compared to healthy young (YH ) individuals. Results show a higher serum inflammatory status of elderly versus young individuals, and especially of ET2DM versus EH . This status is associated with a reduced response to the seasonal influenza vaccine and with increased frequencies of the circulating pro-inflammatory B cell subset called Double Negative (DN) B cells. B cells from ET2DM patients are not only more inflammatory but also hyper-metabolic as compared to those from EH controls. The results herein are to our knowledge the first to show that T2DM superimposed on aging further increases systemic and B cell intrinsic inflammation, as well as dysfunctional humoral immunity. Our findings confirm and extend our previously published findings showing that inflammatory B cells are metabolically supported. [ABSTRACT FROM AUTHOR]- Published
- 2024
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23. Dynamics of Activation and Regulation of the Immune Response to Attack by Viral Pathogens Using Mathematical Modeling.
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Cuesta-Herrera, Ledyz, Pastenes, Luis, Arencibia, Ariel D., Córdova-Lepe, Fernando, and Montoya, Cristhian
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REGULATORY T cells ,IMMUNOREGULATION ,CYTOTOXIC T cells ,B cells ,SARS-CoV-2 ,T cells ,HOMEOSTASIS - Abstract
In this paper, a mathematical model is developed to simulate the activation of regulatory T lymphocytes dynamics. The model considers the adaptive immune response and consists of epithelial cells, infected cells, free virus particles, helper and cytotoxic T lymphocytes, B lymphocytes, and regulatory T lymphocytes. A mathematical analysis was carried out to discuss the conditions of existence and stability of equilibrium solutions in terms of the basic reproductive number. In addition, the definitions and properties necessary to preserve the positivity and stability of the model are shown. The precision of these mathematical models can be affected by numerous sources of uncertainty, partly due to the balance between the complexity of the model and its predictive capacity to depict the biological process accurately. Nevertheless, these models can provide remarkably perspectives on the dynamics of infection and assist in identification specific immunological traits that improve our comprehension of immune mechanisms. The theoretical results are validated by numerical simulations using data reported in the literature. The construction, analysis, and simulation of the developed models demonstrate that the increased induced regulatory T lymphocytes effectively suppress the inflammatory response in contrast to similar cells at lower contents, playing a key role in maintaining self-tolerance and immune homeostasis. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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24. The challenges and breakthroughs in the development of diagnostic monoclonal antibodies.
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Wang, Jing, Song, Qitao, Yang, Tao, Li, Yuanli, Zhang, Lihua, Li, Jiayan, Liu, Feifei, Lin, Yanyin, Xu, Xiaoxia, Heng, Yu, Xu, Lulai, Zhang, Shun, Zhou, Jiahui, Liu, Yunbo, Kong, Lingyuan, Tang, Dingbin, Ji, Chengdong, Tan, Bing, Liao, Pu, and Pan, Nengke
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MONOCLONAL antibodies ,B cells ,ARTIFICIAL intelligence ,SYNTHETIC antibodies ,ANTIBODY formation ,TECHNOLOGICAL innovations ,DISPLAY systems ,MACHINE learning - Abstract
Over the past century, the field of antibody discovery has undergone significant evolution, excluding the current exploration stage of artificial intelligence‐based antibody generation and the often overlooked non‐animal sourced antibody discovery, which typically requires mature in vitro affinity and the selection of high‐quality antigen formulations. This journey has traversed various stages, from methods involving serum‐based antibody acquisition, the isolation of B cells capable of perpetual antibody production through hybridoma technology, to the in‐depth exploration of genetic material using the phage display system, and the current stage involving diverse single B cell screening techniques. Additionally, the emergence of machine learning has brought impressive scientific and technological breakthroughs across research domains, proving to be a powerful application in the field of antibody discovery. However, each technique comes with its limitations, such as variability and control challenges in serum‐based acquisition, lengthy and difficult hybridoma‐derived antibody development, potential limitations in sequence and epitope diversity due to immunization biases in phage display techniques, and costly single B cell screening. Protein mass spectrometry sequencing, with shorter acquisition time and lower costs, is seen as a shortcut by diagnostic companies, impacting traditional antibody development. In diagnostic antibody development, methodological differences in downstream assays and the impact of constant regions outside the Fv core are often neglected. This paper deeply analyzes challenges, proposing innovative strategies for the next generation of diagnostic antibody development. Aimed at moving closer to the gold standard of antibody discovery, these strategies enhance the competitiveness of diagnostic reagent products. [ABSTRACT FROM AUTHOR]
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- 2024
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25. Peritumoral B cells drive proangiogenic responses in HMGB1-enriched esophageal squamous cell carcinoma
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Ying Wang, Reshma Shakya, Anthony Wing Ip Lo, Rajiv Khanna, Ka Chun Wu, Xin Yuan Guan, Leo Y. C. Yan, Dora L.W. Kwong, Yanru Qin, Wei Dai, Simon Law, Ngar-Woon Kam, and Victor Ho-Fun Lee
- Subjects
Cancer Research ,Esophageal Neoplasms ,Physiology ,Angiogenesis ,medicine.medical_treatment ,Clinical Biochemistry ,chemical and pharmacologic phenomena ,HMGB1 ,Umbilical vein ,Transcriptome ,Mice ,High-mobility group box 1 ,Esophageal squamous cell carcinoma ,Cell Line, Tumor ,medicine ,Human Umbilical Vein Endothelial Cells ,Tumor Microenvironment ,Animals ,Humans ,HMGB1 Protein ,Cell Proliferation ,Tube formation ,Tumor microenvironment ,Original Paper ,B cells ,biology ,Neovascularization, Pathologic ,Chemistry ,Glycyrrhizic Acid ,Gene Expression Regulation, Neoplastic ,Cytokine ,Cell culture ,Cancer research ,biology.protein - Abstract
Several B-cell subsets with distinct functions and polarized cytokine profiles that extend beyond antibody production have been reported in different cancers. Here we have demonstrated that proliferating B cells were predominantly found in the peritumoral region of esophageal squamous cell carcinoma (ESCC). These B cells were enriched in tumor nests with high expression of high-mobility group box 1 (HMGB1). High densities of peritumoral proliferating B cells and concomitantly high intratumoral HMGB1 expression showed improved prognostic significance, surpassing prognostic stratification of ESCC patients based on HMGB1 positivity alone. This striking association led us to set up models to test whether cancer-derived HMGB1 could shape tumor microenvironment via modulation on B cells. Overexpression of HMGB1 in ESCC cell lines (KYSE510 and EC18) enhanced proliferation and migration of B cells. Transcriptomic analysis showed that migratory B cells exhibited high enrichment of proangiogenic genes. VEGF expression in proliferating B cells was induced upon co-culture of HMGB1-overexpressing tumor cells and B cells. Secretome array profiling of conditioned media (CM) from the co-culture revealed rich expression of proangiogenic proteins. Consequently, incubation of human umbilical vein endothelial cells with CM promoted angiogenesis in tube formation and migration assays. HMGB1 inhibitor, glycyrrhizin, abolishes all the observed proangiogenic phenotypes. Finally, co-injection of B cells and CM with HMGB1-overexpressing tumor cells, but not with glycyrrhizin, significantly enhanced tumor growth associated with increased microvascular density in ESCC xenograft mice model. Our results indicate that cancer-derived HMGB1 elevates angiogenesis in ESCC by shifting the balance toward proangiogenic signals in proliferating B cells. Supplementary Information The online version contains supplementary material available at 10.1007/s10456-021-09819-0.
- Published
- 2021
26. Licochalcone A improves the cognitive ability of mice by regulating T- and B-cell proliferation
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Yating Wu, Haifeng Liu, Jianbo Zhu, and Hailiang Liu
- Subjects
Aging ,Licochalcone A ,T-Lymphocytes ,T cells ,Morris water navigation task ,Spleen ,Pharmacology ,Flow cytometry ,chemistry.chemical_compound ,Mice ,Immune system ,Chalcones ,Cognition ,cognitive ability ,medicine ,Animals ,Maze Learning ,Whole blood ,Cell Proliferation ,B cells ,B-Lymphocytes ,medicine.diagnostic_test ,licochalcone A ,Interleukin-17 ,Interleukin ,Cell Biology ,Mice, Inbred C57BL ,medicine.anatomical_structure ,chemistry ,Cerebral blood flow ,Research Paper - Abstract
Licochalcone A (LA), a flavonoid found in licorice, has anticancer, antioxidant, anti-inflammatory, and neuroprotective properties. Here, we explored the effect of injecting LA into the tail vein of middle-aged C57BL/6 mice on their cognitive ability as measured by the Morris water maze (MWM) test and cerebral blood flow (CBF). The related mechanisms were assessed via RNA-seq, and T (CD3e+) and B (CD45R/B220+) cells in the spleen and whole blood were quantified via flow cytometry. LA improved the cognitive ability, according to the MWM test results, and upregulated the CBF level of treated mice. The RNA-seq results indicate that LA affected the interleukin (IL)-17 signaling pathway, which is related to T- and B-cell proliferation, and the flow cytometry data suggest that LA promoted T- and B-cell proliferation in the spleen and whole blood. We also performed immune reconstruction via a tail vein injection of lymphocytes into B-NDG (NOD-PrkdcscidIl2rgtm1/Bcge) mice before treating them with LA. We tested cognitive ability by subjecting these animals to new object recognition tests and quantified the splenic and whole blood T and B cells. Cognitive ability improved after immune reconstruction and LA treatment, and LA promoted T- and B-cell proliferation in the spleen and whole blood. This study demonstrates that LA, by activating the IL-17 signaling pathway, promotes T- and B-cell proliferation in the spleen and whole blood of mice and improves cognitive ability. Thus, LA may have immune-modulating therapeutic potential for improving cognition.
- Published
- 2021
27. Anti-Idiotypic mRNA Vaccine to Treat Autoimmune Disorders.
- Author
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Niazi, Sarfaraz K.
- Subjects
AUTOIMMUNE diseases ,MESSENGER RNA ,AUTOANTIBODIES ,B cells ,T cells - Abstract
The 80+ existing autoimmune disorders (ADs) affect billions with little prevention or treatment options, except for temporary symptomatic management, leading to enormous human suffering and a monumental financial burden. The autoantibodies formed in most ADs have been identified, allowing the development of novel anti-idiotypic antibodies to mute the autoantibodies using vaccines. Nucleoside vaccines have been successfully tested as antigen-specific immunotherapies (ASI), with mRNA technology offering multi-epitope targeting to mute multiple autoantibodies. This paper proposes using mRNA technology to produce anti-idiotypic antibodies with broad effectiveness in preventing and treating them. This paper delves into the state-of-the-art mRNA design strategies used to develop novel ASIs by selecting appropriate T cell and B cell epitopes to generate anti-idiotypic antibodies. The low cost and fast development of mRNA vaccines make this technology the most affordable for the global control of ADs. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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28. Lupus nephritis: clinical presentations and outcomes in the 21st century
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Gabriella Moroni, Andrea Doria, Michela Gasparotto, Mariele Gatto, and Valentina Binda
- Subjects
medicine.medical_specialty ,030232 urology & nephrology ,Lupus nephritis ,B cells ,calcineurin inhibitors ,classification ,lupus nephritis ,prognosis ,renal biopsy ,risk factors ,Unmet needs ,End stage renal disease ,03 medical and health sciences ,0302 clinical medicine ,Rheumatology ,Recurrence ,Epidemiology ,medicine ,Humans ,Pharmacology (medical) ,Intensive care medicine ,AcademicSubjects/MED00360 ,Disease prognosis ,030203 arthritis & rheumatology ,business.industry ,Mortality rate ,Remission Induction ,Retrospective cohort study ,medicine.disease ,Precision medicine ,Supplement Papers ,Disease Progression ,business - Abstract
Lupus nephritis (LN) is a frequent and severe manifestation of SLE. Along the decades, the epidemiology of LN and its clinical presentation have been changing. However, even though retrospective cohort studies report a decreased mortality rate and an improvement in the disease prognosis, the percentage of patients progressing into end stage renal disease (ESRD) keeps steady despite the improvements in therapeutic strategies. Current in-use medications have been available for decades now, yet over the years, regimens for optimizing their efficacy and minimizing toxicity have been developed. Therapeutic research is now moving towards the direction of precision medicine and several new drugs, targeting selectively different pathogenetic pathways, are currently under evaluation with promising results. In this review, we address the main changes and persistent unmet needs in LN management throughout the past decades, with a focus on prognosis and upcoming treatments.
- Published
- 2020
29. B cells do not play a role in vaccine-mediated immunity against Marek’s disease
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Mohammad Heidari, Huanmin Zhang, Cari Hearn, and Lakshmi Sunkara
- Subjects
Marek’s disease ,B cells ,Infectious Diseases ,General Veterinary ,General Immunology and Microbiology ,Regular paper ,Bursectomy ,Vaccination ,Public Health, Environmental and Occupational Health ,Molecular Medicine ,Immunologic diseases. Allergy ,RC581-607 ,Marek’s disease virus - Abstract
Background: Marek’s disease virus (MDV), a highly oncogenic α-herpesvirus, is the etiological agent of Marek’s disease (MD) in chickens. The antiviral activity of vaccine-induced immunity against MD reduces the level of early cytolytic infection, production of cell-free virions in the feather follicle epithelial cells (FFE), and lymphoma formation. Despite the success of several vaccines that have greatly reduced the economic losses from MD, the mechanism of vaccine-induced immunity is poorly understood. Methods: To provide insight into possible role of B cells in vaccine-mediated protection, we bursectomized birds on day of hatch and vaccinated them eight days later. The birds were challenged 10 days post vaccination with or without receiving adoptive lymphocytes from age-matched control birds prior to inoculation. The study also included vaccinated/challenged and non-vaccinated challenged intact birds. Flowcytometric analysis of PBMN cells were conducted twice post bursectomy to confirm B cell depletion and assess the effect of surgery on T cell population. Immunohistochemical analysis and viral genome copy number assessment in the skin samples at termination was performed to measure the replication rate of MDV in the FFE of the skin tissues of the challenged birds. Results: The non-vaccinated/challenged birds developed typical clinical signs of MD while the vaccinated/challenged and bursectomized, vaccinated/challenged groups with or without adoptive lymphocyte transfer, were fully protected with no sign of transient paralysis, weight loss, or T cell lymphomas. Immunohistochemical analysis and viral genome copy number evaluation in the skin samples revealed that unlike the vaccinated/challenged birds a significant number of virus particles were produced in the FFE of the non-vaccinated/challenged birds at termination. In the bursectomized, vaccinated/challenged groups, only a few replicating virions were detected in the skin of birds that received adoptive lymphocytes prior to challenge. Conclusions: The study shows that B cells do not play a critical role in MD vaccine-mediated immunity.
- Published
- 2022
30. Dimethyl fumarate treatment shifts the immune environment toward an anti-inflammatory cell profile while maintaining protective humoral immunity
- Author
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Mark Cascione, Chongshu Chen, Tomasz Zielinski, Catherine Miller, Becky Parks, David Brassat, Shivani Kapadia, Yang Mao-Draayer, Diana Xing, Derrick Robertson, Erin E. Longbrake, Eris Bame, and Jason P. Mendoza
- Subjects
lymphocytes ,medicine.drug_class ,Dimethyl Fumarate ,Cell ,Anti-Inflammatory Agents ,multiple sclerosis ,Anti-inflammatory ,03 medical and health sciences ,chemistry.chemical_compound ,Multiple Sclerosis, Relapsing-Remitting ,0302 clinical medicine ,Immune system ,medicine ,Humans ,Prospective Studies ,Delayed-release dimethyl fumarate ,030304 developmental biology ,B cells ,0303 health sciences ,Dimethyl fumarate ,biology ,Multiple sclerosis ,Absolute lymphocyte count ,medicine.disease ,Immunity, Humoral ,medicine.anatomical_structure ,Neurology ,chemistry ,Immunology ,Humoral immunity ,biology.protein ,Neurology (clinical) ,Neoplasm Recurrence, Local ,Antibody ,Original Research Papers ,immunoglobulin ,Immunosuppressive Agents ,030217 neurology & neurosurgery - Abstract
Background: Delayed-release dimethyl fumarate (DMF) demonstrates sustained efficacy and safety for relapsing forms of MS. Absolute lymphocyte count (ALC) is reduced initially, then stabilizes on treatment. Objective: PROCLAIM, a 96-week, prospective, open-label, phase 3b study, assessed lymphocyte subsets and immunoglobulin (Ig) levels during 48 and 96 weeks (W) of DMF treatment. Methods: Patients received 240 mg DMF BID. Endpoints: lymphocyte subset count changes (primary); Ig isotypes and ALC changes (secondary); adverse events and relationship between ALC changes and ARR/EDSS (exploratory); and neurofilament assessment (ad hoc). Results: Of 218 patients enrolled, 158 (72%) completed the study. Median ALC decreased 39% from baseline to W96 (BL–W96), stabilizing above the lower limit of normal (baseline: 1.82 × 109/L; W48: 1.06 × 109/L; W96: 1.05 × 109/L). CD4 + and CD8 + T cells correlated highly with ALC from BL–W96 ( p + and CD8 + T cells increased, whereas CD4 + and CD8 + central and effector memory T cells decreased. Total IgA, IgG, IgM, and IgG1–4 subclass levels remained stable. Adverse event rates were similar across ALC subgroups. ARR, EDSS, and neurofilament were not correlated with ALCs. Conclusion: Lymphocyte decreases with DMF were maintained over treatment, yet immunoglobulins remained stable. No increase in infection incidence was observed in patients with or without lymphopenia. Support: Biogen
- Published
- 2020
31. Interleukin 39: a new member of interleukin 12 family
- Author
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Keye Xu, Xiaoying Wang, Zhiyu Lu, Mingcai Li, and Yan Li
- Subjects
Review Paper ,B cells ,biology ,Chemistry ,Immunology ,Interleukin ,Inflammation ,EBI3 ,Glycoprotein 130 ,Molecular biology ,acute coronary syndrome ,03 medical and health sciences ,0302 clinical medicine ,systemic lupus erythematosus ,medicine ,Interleukin 12 ,STAT protein ,biology.protein ,Immunology and Allergy ,interleukin 12 ,medicine.symptom ,Receptor ,STAT3 ,interleukin 39 ,030215 immunology - Abstract
Interleukin (IL)-12 family member is a heterodimer glycoprotein, composed of two covalently linked subunits, α and β chains. The α subunit consists of IL-23p19, IL-27p28, and IL-12p35, and the β subunit includes IL-12p40 and Epstein-Barr virus-induced gene (Ebi3). IL-39 is a new heterodimeric IL-12 family member composed of IL-23p19 and Ebi3 subunits. IL-39 is secreted by lipopolysaccharide-stimulated B cells. Other immune cells, such as dendritic cells and macrophages, express IL-39 mRNA. In lupus-like mice, GL7+B cells and CD138+plasma cells are highly activated and widely expressed, promoting high expression of IL-39. IL-39 mediates inflammatory responses through binding to a heterodimer of IL-23R/gp130 receptor and activation of signal transducer and activator of transcription (STAT)1/STAT3 signal molecules. The serum levels of IL-39 were significantly increased in patients with acute coronary syndrome compared with patients with normal coronary arteries. This review discusses the biological characteristics, receptor, and signal pathway as well as biological activity of IL-39 and its potential role in inflammation and other diseases.
- Published
- 2020
32. Method for B Cell Receptor Enrichment in Malignant B Cells.
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Bhattacharyya, Puja, Christopherson, Richard I., Skarratt, Kristen K., and Fuller, Stephen J.
- Subjects
PROTEIN analysis ,RESEARCH funding ,IMMUNE system ,ANTIGENS ,MASS spectrometry ,PROTEOMICS ,B cells - Abstract
Simple Summary: The B cell receptor (BCR) is a membrane-bound protein complex that is required for the normal development of B cells. BCR signalling is also involved in the pathogenesis of B cell cancers. While there is substantial literature on genomic analyses of the BCR, there are limited proteomic studies of receptor structure and its interactions with neighbouring proteins. This is partly due to the location of the BCR in the surface-membrane lipid environment that has limited the ability to enrich the complex for proteomic analysis. Here, we report an enrichment technique that can be used for mass spectrometry analyses of the BCR from live B cells. B cells are central to the adaptive immune response and provide long-lasting immunity after infection. B cell activation is mediated by the surface membrane-bound B cell receptor (BCR) following recognition of a specific antigen. The BCR has been challenging to analyse using mass spectrometry (MS) due to the difficulty of isolating and enriching this membrane-bound protein complex. There are approximately 120,000 BCRs on the B cell surface; however, depending on the B cell activation state, there may be hundreds-of-millions to billions of proteins in a B cell. Consequently, advanced proteomic techniques such as MS workflows that use purified proteins to yield structural and protein-interaction information have not been published for the BCR complex. This paper describes a method for enriching the BCR complex that is MS-compatible. The method involves a Protein G pull down on agarose beads using an intermediary antibody to each of the BCR complex subcomponents (CD79a, CD79b, and membrane immunoglobulin). The enrichment process is shown to pull down the entire BCR complex and has the advantage of being readily compatible with further proteomic study including MS analysis. Using intermediary antibodies has the potential to enrich all isotypes of the BCR, unlike previous methods described in the literature that use protein G-coated beads to directly pull down the membrane IgG (mIgG) but cannot be used for other mIg isotypes. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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33. EXPERIMENTAL PLAN BASED ON THE RANDOMIZED COMPLETE BLOCK METHOD FOR THE DEVELOPMENT OF FLEXIBLE MATERIALS FOR ELECTROMAGNETIC ATTENUATION.
- Author
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Raluca Maria, AILENI, Cornel Adrian, MARIN, and Laurentiu Cristian, DINCA
- Subjects
ELECTROMAGNETIC waves ,ELECTROMAGNETIC shielding ,KILLER cells ,ELECTROMAGNETIC devices ,B cells - Abstract
The negative effects of continuous exposure to electromagnetic waves know a continuous growth on the last years because of new developments in electronics and mobile communication applications in different fields (medical, smart devices for IoT applications). There are some researches concluding that exposure to electromagnetic fields could affect the cells (PMBCs, T lymphocytes, B lymphocytes, NK cells and macrophages) of the immune system including cell proportion, cell cycle, apoptosis, destruction activity and cytokine content. Considering the negative effect of electromagnetic inference, it is necessary to develop advanced materials to attenuate electromagnetic waves to protect electronic equipment and humans. In this context, this paper presents an experimental plan based on completely randomized blocks (RCBD) for obtaining adequate textile coating for electromagnetic shielding applications taking into account the design of electromagnetic shielding devices should include the modelling of the attenuation phenomenon of electromagnetic waves using Schelkunoff and Calculation theories. The proposed experimental plan consists of experiments distributed in blocks, each block corresponding to the technology used. For each experimental block, the factors specific to the technology used (independent variables such as the metals used (Ni, Cu, graphite, Fe3O4, Ag, Zn), mass (M), air permeability (Pa), thickness (d)) that could influence the response variable (electrical resistance (Rs)) have been taken into consideration. [ABSTRACT FROM AUTHOR]
- Published
- 2024
34. The Lung in Rheumatoid Arthritis—Friend or Enemy?
- Author
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Anton, Maria-Luciana, Cardoneanu, Anca, Burlui, Alexandra Maria, Mihai, Ioana Ruxandra, Richter, Patricia, Bratoiu, Ioana, Macovei, Luana Andreea, and Rezus, Elena
- Subjects
LUNGS ,RHEUMATOID arthritis ,CHEMOKINE receptors ,INTERSTITIAL lung diseases ,SYNOVIAL membranes ,B cells ,IMMUNE system - Abstract
Rheumatoid arthritis (RA) is a chronic autoimmune condition frequently found in rheumatological patients that sometimes raises diagnosis and management problems. The pathogenesis of the disease is complex and involves the activation of many cells and intracellular signaling pathways, ultimately leading to the activation of the innate and acquired immune system and producing extensive tissue damage. Along with joint involvement, RA can have numerous extra-articular manifestations (EAMs), among which lung damage, especially interstitial lung disease (ILD), negatively influences the evolution and survival of these patients. Although there are more and more RA-ILD cases, the pathogenesis is incompletely understood. In terms of genetic predisposition, external environmental factors act and subsequently determine the activation of immune system cells such as macrophages, neutrophils, B and T lymphocytes, fibroblasts, and dendritic cells. These, in turn, show the ability to secrete molecules with a proinflammatory role (cytokines, chemokines, growth factors) that will produce important visceral injuries, including pulmonary changes. Currently, there is new evidence that supports the initiation of the systemic immune response at the level of pulmonary mucosa where the citrullination process occurs, whereby the autoantibodies subsequently migrate from the lung to the synovial membrane. The aim of this paper is to provide current data regarding the pathogenesis of RA-associated ILD, starting from environmental triggers and reaching the cellular, humoral, and molecular changes involved in the onset of the disease. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
35. The Functional Mechanism of BP9 in Promoting B Cell Differentiation and Inducing Antigen Presentation.
- Author
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Hu, Jianing, Zhang, Ze, Cai, Jiaxi, Hao, Shanshan, Li, Chenfei, and Feng, Xiuli
- Subjects
B cell differentiation ,ANTIGEN presentation ,PLASMA cells ,B cells ,CELL differentiation - Abstract
The Bursa of Fabricius, an avian unique humoral immune organ, is instrumental to B cell development. Bursal-derived peptide BP9 fosters B-cell development and formation. Yet, the exact mechanism wherein BP9 impacts B cell differentiation and antigenic presentation remains undefined. In this paper, B cell activation and differentiation in the spleen cells from mice immunized with the AIV vaccine and BP9 were detected following flow cytometry (FCM) analysis. Furthermore, the molecular mechanism of BP9 in B cell differentiation in vivo was investigated with RNA sequencing technology. To verify the potential functional mechanism of BP9 in the antigenic presentation process, the transcriptome molecular basis of chicken macrophages stimulated by BP9 was measured via high-throughput sequencing technology. The results proved that when given in experimental dosages, BP9 notably accelerated total B cells, and enhanced B-cell differentiation and plasma cell production. The gene expression profiles of B cells from mice immunized with 0.01 mg/mL BP9 and AIV vaccine disclosed that 0.01 mg/mL BP9 initiated the enrichment of several biological functions and significantly stimulated key B-cell pathways in immunized mice. Crucially, a total of 4093 differentially expressed genes were identified in B cells with BP9 stimulation, including 943 upregulated genes and 3150 downregulated genes. Additionally, BP9 induced various cytokine productions in the chicken macrophage HD11 cells and activated 9 upregulated and 20 downregulated differential miRNAs, which were involved in various signal and biological processes. Furthermore, BP9 stimulated the activation of multiple transcription factors in HD11 cells, which was related to antigen presentation processes. In summary, these results suggested that BP9 might promote B cell differentiation and induce antigen presentation, which might provide the valuable insights into the mechanism of B cell differentiation upon bursal-derived immunomodulating peptide stimulation and provide a solid experimental groundwork for enhancing vaccine-induced immunity. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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36. Cadmium Exposure: Mechanisms and Pathways of Toxicity and Implications for Human Health.
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Qu, Fei and Zheng, Weiwei
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MITOGEN-activated protein kinases ,CADMIUM ,EPIGENOMICS ,POISONS ,CELL anatomy ,CELL communication ,B cells ,HISTONES - Abstract
Cadmium (Cd), a prevalent environmental contaminant, exerts widespread toxic effects on human health through various biochemical and molecular mechanisms. This review encapsulates the primary pathways through which Cd inflicts damage, including oxidative stress induction, disruption of Ca
2+ signaling, interference with cellular signaling pathways, and epigenetic modifications. By detailing the absorption, distribution, metabolism, and excretion (ADME) of Cd, alongside its interactions with cellular components such as mitochondria and DNA, this paper highlights the extensive damage caused by Cd2+ at the cellular and tissue levels. The role of Cd in inducing oxidative stress—a pivotal mechanism behind its toxicity—is discussed with emphasis on how it disrupts the balance between oxidants and antioxidants, leading to cellular damage and apoptosis. Additionally, the review covers Cd's impact on signaling pathways like Mitogen-Activated Protein Kinase (MAPK), Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB), and Tumor Protein 53 (p53) pathways, illustrating how its interference with these pathways contributes to pathological conditions and carcinogenesis. The epigenetic effects of Cd, including DNA methylation and histone modifications, are also explored to explain its long-term impact on gene expression and disease manifestation. This comprehensive analysis not only elucidates the mechanisms of Cd toxicity but also underscores the critical need for enhanced strategies to mitigate its public health implications. [ABSTRACT FROM AUTHOR]- Published
- 2024
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37. Unravelling B cell heterogeneity: insights into flow cytometrygated B cells from single-cell multi-omics data.
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Pernes, Jane I., Alsayah, Atheer, Tucci, Felicia, and Bashford-Rogers, Rachael J. M.
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B cells ,MULTIOMICS ,CELL populations ,CELL physiology ,HETEROGENEITY - Abstract
Introduction: B cells play a pivotal role in adaptive immunity which has been extensively characterised primarily via flow cytometry-based gating strategies. This study addresses the discrepancies between flow cytometry-defined B cell subsets and their high-confidence molecular signatures using single-cell multiomics approaches. Methods: By analysing multi-omics single-cell data from healthy individuals and patients across diseases, we characterised the level and nature of cellular contamination within standard flow cytometric-based gating, resolved some of the ambiguities in the literature surrounding unconventional B cell subsets, and demonstrated the variable effects of flow cytometric-based gating cellular heterogeneity across diseases. Results: We showed that flow cytometric-defined B cell populations are heterogenous, and the composition varies significantly between disease states thus affecting the implications of functional studies performed on these populations. Importantly, this paper draws caution on findings about B cell selection and function of flow cytometric-sorted populations, and their roles in disease. As a solution, we developed a simple tool to identify additional markers that can be used to increase the purity of flow-cytometric gated immune cell populations based on multi-omics data (AlliGateR). Here, we demonstrate that additional non-linear CD20, CD21 and CD24 gating can increase the purity of both naïve and memory populations. Discussion: These findings underscore the need to reconsider B cell subset definitions within the literature and propose leveraging single-cell multi-omics data for refined characterisation. We show that single-cell multi-omics technologies represent a powerful tool to bridge the gap between surface marker-based annotations and the intricate molecular characteristics of B cell subsets. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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38. The ‘best’ basic science paper on multiple sclerosis in 2012.
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Mahad, Don
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- *
MEDICAL sciences , *B cells , *MENINGEAL artery , *INFLAMMATION ,MULTIPLE sclerosis research - Abstract
The article focuses on the best basic science research on multiple sclerosis (MS) in 2012. It states several researchers working on MS, including S. R. Choi and colleagues on the role of meningeal inflammation in MS, R. P. Lisak and colleagues on the contribution of B cells to the grey matter (GM) pathology of MS, and A. Chang and colleagues on the effect of remyelination in MS. It says that the work of Robin Franklin's group on enhanced remyelination in MS is the best research in 2012.
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- 2013
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39. Genomic, transcriptomic and epigenomic sequencing data of the B-cell leukemia cell line REH.
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Lysenkova Wiklander, Mariya, Övernäs, Elin, Lagensjö, Johanna, Raine, Amanda, Petri, Anna, Wiman, Ann-Christin, Ramsell, Jon, Marincevic-Zuniga, Yanara, Gezelius, Henrik, Martin, Tom, Bunikis, Ignas, Ekberg, Sara, Erlandsson, Rikard, Larsson, Pontus, Mosbech, Mai-Britt, Häggqvist, Susana, Hellstedt Kerje, Susanne, Feuk, Lars, Ameur, Adam, and Liljedahl, Ulrika
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B cells ,WHOLE genome sequencing ,TRANSCRIPTOMES ,RNA sequencing ,LYMPHOBLASTIC leukemia ,LEUKEMIA - Abstract
Objectives: The aim of this data paper is to describe a collection of 33 genomic, transcriptomic and epigenomic sequencing datasets of the B-cell acute lymphoblastic leukemia (ALL) cell line REH. REH is one of the most frequently used cell lines for functional studies of pediatric ALL, and these data provide a multi-faceted characterization of its molecular features. The datasets described herein, generated with short- and long-read sequencing technologies, can both provide insights into the complex aberrant karyotype of REH, and be used as reference datasets for sequencing data quality assessment or for methods development. Data description: This paper describes 33 datasets corresponding to 867 gigabases of raw sequencing data generated from the REH cell line. These datasets include five different approaches for whole genome sequencing (WGS) on four sequencing platforms, two RNA sequencing (RNA-seq) techniques on two different sequencing platforms, DNA methylation sequencing, and single-cell ATAC-sequencing. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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40. Compromised steady‐state germinal center activity with age in nonhuman primates
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Francois Villinger, Tirupataiah Sirupangi, Rajendra Pahwa, Lucio Gama, Kimberly Shankwitz, Kyle Blaine Russel, Constantinos Petrovas, Suresh Pallikkuth, Savita Pahwa, Richard A. Koup, Daniel Kvistad, and Li Pan
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CD4-Positive T-Lymphocytes ,0301 basic medicine ,Aging ,medicine.medical_specialty ,Cell ,CD8-Positive T-Lymphocytes ,Biology ,Positive correlation ,Monocytes ,law.invention ,03 medical and health sciences ,follicles ,0302 clinical medicine ,Immune system ,Antigens, CD ,law ,Internal medicine ,Follicular phase ,medicine ,Animals ,Cytotoxic T cell ,Inflammation ,B-Lymphocytes ,Original Paper ,B cells ,Germinal center ,Forkhead Transcription Factors ,Cell Biology ,Germinal Center ,Macaca mulatta ,Lymphocyte Activation Gene 3 Protein ,Original Papers ,Immunity, Humoral ,030104 developmental biology ,Endocrinology ,medicine.anatomical_structure ,Suppressor ,Lymph Nodes ,Steady state (chemistry) ,Tfh cells ,030217 neurology & neurosurgery ,Granulocytes - Abstract
Age‐related reductions in vaccine‐induced B cells in aging indicate that germinal centers (GCs), the anatomical site where the development of humoral responses takes place, may lose efficacy with age. We have investigated the baseline follicular and GC composition in nonhuman primates (NHPs) with respect to their age. There was a marked reduction in follicular area in old animals. We found significantly lower normalized numbers of follicular PD1hi CD4 T (Tfh) and proliferating (Ki67hi) GC B cells with aging, a profile associated with significantly higher numbers of potential follicular suppressor FoxP3hiLag3hi CD4 T cells. Furthermore, a positive correlation was found between Tfh and follicular CD8 T cells (fCD8) only in young animals. Despite the increased levels of circulating preinflammatory factors in aging, young animals had higher numbers of monocytes and granulocytes in the follicles, a profile negatively associated with numbers of Tfh cells. Multiple regression analysis showed an altered association between GC B cells and other GC immune cell populations in old animals suggesting a differential mechanistic regulation of GC activity in aging. Our data demonstrate defective baseline GC composition in old NHPs and provide an immunological base for further understanding the adaptive humoral responses with respect to aging., Steady‐state germinal center immune reactivity is compromised in aged NHPs. This loss of reactivity is characterized by changes in many GC associated cell populations including Tfh, B cells, and follicular Tregs.
- Published
- 2019
41. Regulation of B cell functions by S-nitrosoglutathione in the EAE model
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Fei Qiao, Avtar K. Singh, Mushfiquddin Khan, Judong Kim, Inderjit Singh, S.M. Touhidul Islam, and Je-Seong Won
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0301 basic medicine ,Adoptive cell transfer ,Medicine (General) ,Encephalomyelitis, Autoimmune, Experimental ,QH301-705.5 ,Regulatory B cells ,medicine.medical_treatment ,T cell ,GSNO ,Clinical Biochemistry ,S-Nitrosoglutathione-reductase ,Biology ,Biochemistry ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Immune system ,R5-920 ,medicine ,Animals ,Biology (General) ,B cell ,GSNOR ,B cells ,IL-6 ,B-Lymphocytes ,Experimental autoimmune encephalomyelitis ,EAE ,Organic Chemistry ,medicine.disease ,Mice, Inbred C57BL ,Interleukin 10 ,030104 developmental biology ,medicine.anatomical_structure ,Cytokine ,Immunology ,IL-10 ,S-Nitrosoglutathione ,Cytokines ,030217 neurology & neurosurgery ,Research Paper - Abstract
B cells play both protective and pathogenic roles in T cell-mediated autoimmune diseases by releasing regulatory vs. pathogenic cytokines. B cell-depleting therapy has been attempted in various autoimmune diseases but its efficacy varies and can even worsen symptoms due to depletion of B cells releasing regulatory cytokines along with B cells releasing pathogenic cytokines. Here, we report that S-nitrosoglutathione (GSNO) and GSNO-reductase (GSNOR) inhibitor N6022 drive upregulation of regulatory cytokine (IL-10) and downregulation of pathogenic effector cytokine (IL-6) in B cells and protected against the neuroinflammatory disease of experimental autoimmune encephalomyelitis (EAE). In human and mouse B cells, the GSNO/N6022-mediated regulation of IL-10 vs. IL-6 was not limited to regulatory B cells but also to a broad range of B cell subsets and antibody-secreting cells. Adoptive transfer of B cells from N6022 treated EAE mice or EAE mice deficient in the GSNOR gene also regulated T cell balance (Treg > Th17) and reduced clinical disease in the recipient EAE mice. The data presented here provide evidence of the role of GSNO in shifting B cell immune balance (IL-10 > IL-6) and the preclinical relevance of N6022, a first-in-class drug targeting GSNOR with proven human safety, as therapeutics for autoimmune disorders including multiple sclerosis., Graphical abstract Image 1, Highlights • GSNO and GSNOR inhibitor (N6022) upregulates IL-10 and downregulates IL-6 in B cells. • GSNO/N6022-mediated cytokine regulation occurs in a broad range of B cell subsets. • GSNO/N6022 treatment ameliorates autoimmune disease of EAE. • B cell transfer from N6022-treated or GSNOR null EAE mice to EAE mice shifts T cell balance (Treg > Th17) and alleviates EAE. • The data provide the first insight into the therapeutic potential of GSNO/N6022 targeting B cells in multiple sclerosis.
- Published
- 2021
42. Inhibition of B cell activation following
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Seung Y, Chu, Erik, Pong, Christine, Bonzon, Ning, Yu, Chaim O, Jacob, Samantha A, Chalmers, Chaim, Putterman, David E, Szymkowski, and William, Stohl
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FcγRIIb ,B cells ,Research paper ,Lupus ,Murine - Abstract
Engagement of Fcγ receptor IIb (FcγRIIb) suppresses B cell activation and represents a promising target for therapy in autoimmunity. Obexelimab is a non-depleting anti-human CD19 mAb with an Fc region engineered to have high affinity for human FcγRIIb, thereby co-engaging BCR and FcγRIIb. To assess its ability to suppress B cell activation in vivo, we generated non-autoimmune-prone C57BL/6 (B6) and SLE-prone NZM 2328 (NZM) mice in which the human FcγRIIb extracellular domain was knocked into the mouse Fcgr2b locus (B6.hRIIb and NZM.hRIIb mice, respectively, the latter retaining features of SLE). XENP8206, a mAb which bears the same FcγRIIb-enhanced human Fc domain as does obexelimab but which recognizes murine CD19 rather than human CD19, inhibited in vitro BCR-triggered activation of B cells from both B6.hRIIb and NZM.hRIIb mice. Following administration of XENP8206 to B6.hRIIb or NZM.hRIIb mice, B cell numbers in the spleen and lymph nodes remained stable but became hyporesponsive to BCR-triggered activation for at least 14 days. These findings demonstrate proof-of-principle that pharmacologic co-engagement of BCR and human FcγRIIb inhibits B cell activation in non-autoimmune and SLE-prone hosts while preserving B cell numbers. These observations lay a strong foundation for clinical trials in human SLE with agents that co-engage BCR and FcγRIIb. Moreover, B6.hRIIb and NZM.hRIIb should serve as powerful in vivo models in the elucidation of the cellular and molecular underpinnings of the changes induced by BCR/FcγRIIb co-engagement., Highlights • We generated non-autoimmune B6.hRIIb and SLE-prone NZM.hRIIb knockin mice for the human FcγRIIb extracellular domain. • XENP8206 is an anti-murine CD19 mAb engineered to have high affinity for human FcγRIIb. • XENP8206 inhibited in vitro BCR-triggered activation of B cells from both B6.hRIIb and NZM.hRIIb mice. • XENP8206 inhibited in vivo BCR-triggered activation of B cells while preserving B cell numbers. • These observations lay a strong foundation for clinical trials in human SLE with agents that co-engage BCR and FcγRIIb.
- Published
- 2020
43. Role of germinal center and CD39highCD73+ B cells in the age-related tonsillar involution.
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Pastor, Rocío, Puyssegur, Juliana, de la Guardia, M. Paula, Varón, Lindybeth Sarmiento, Beccaglia, Gladys, Spada, Nicolás, de Lima, Andrea Paes, Collado, M. Soledad, Blanco, Andrés, Scetti, Isabel Aspe, Arabolaza, M. Elena, Paoli, Bibiana, Chirdo, Fernando, and Arana, Eloísa
- Subjects
B cells ,GERMINAL centers ,IMMUNOLOGIC memory ,T helper cells ,MUCOUS membranes - Abstract
Background: The tonsils operate as a protection ring of mucosa at the gates of the upper aero-digestive tract. They show similarities with lymph nodes and participate as inductive organs of systemic and mucosal immunity. Based on the reduction of their size since puberty, they are thought to experience involution in adulthood. In this context, we have used tonsillar mononuclear cells (TMC) isolated from patients at different stages of life, to study the effect of ageing and the concomitant persistent inflammation on these immune cells. Results: We found an age-dependent reduction in the proportion of germinal center B cell population (B
GC ) and its T cell counterpart (T follicular helper germinal center cells, TfhGC ). Also, we demonstrated an increment in the percentage of local memory B cells and mantle zone T follicular helper cells (mTfh). Furthermore, younger tonsils rendered higher proportion of proliferative immune cells within the freshly isolated TMC fraction than those from older ones. We demonstrated the accumulation of a B cell subset (CD20+ CD39high CD73+ cells) metabolically adapted to catabolize adenosine triphosphate (ATP) as patients get older. To finish, tonsillar B cells from patients at different ages did not show differences in their proliferative response to stimulation ex vivo, in bulk TMC cultures. Conclusions: This paper sheds light on the changing aspects of the immune cellular landscape, over the course of time and constant exposure, at the entrance of the respiratory and digestive systems. Our findings support the notion that there is a re-modelling of the immune functionality of the excised tonsils over time. They are indicative of a transition from an effector type of immune response, typically oriented to reduce pathogen burden early in life, to the development of an immunosuppressive microenvironment at later stages, when tissue damage control gets critical provided the time passed under immune attack. Noteworthy, when isolated from such histologic microenvironment, older tonsillar B cells seem to level their proliferation capacity with the younger ones. Understanding these features will not only contribute to comprehend the differences in susceptibility to pathogens among children and adults but would also impact on vaccine developments intended to target these relevant mucosal sites. [ABSTRACT FROM AUTHOR]- Published
- 2024
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- View/download PDF
44. CD4
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Jian, Lu, Jing, Wu, Feiting, Xie, Jie, Tian, Xinyi, Tang, Hongye, Guo, Jie, Ma, Ping, Xu, Lingxiang, Mao, Huaxi, Xu, and Shengjun, Wang
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B cells ,Full Paper ,HBsAg vaccine ,CD40L ,Full Papers ,extracellular vesicles ,CD4+ T cells - Abstract
T cells secrete bioactive extracellular vesicles (EVs), but the potential biological effects of CD4+ T cell EVs are not clear. The main purpose of this study is to investigate the effects of CD4+ T cell–derived EVs on B cell responses and examine their role in antigen‐mediated humoral immune responses. In this study, CD4+ T cell EVs are purified from activated CD4+ T cells in vitro. After immunization with the Hepatitis B surface antigen (HBsAg) vaccine, CD4+ T cell EVs‐treated mice show stronger humoral immune responses, which is indicated by a greater Hepatitis B surface antibody (HBsAb) level in serum and a greater proportion of plasma cells in bone marrow. In addition, it is found that EVs released from activated CD4+ T cells play an important role in B cell responses in vitro, which significantly promote B cell activation, proliferation, and antibody production. Interestingly, antigen‐specific CD4+ T cell EVs are found to be more efficient than control EVs in enhancing B cell responses. Furthermore, it is shown that CD40 ligand (CD40L) is involved in CD4+ T cell EVs‐mediated B cell responses. Overall, the results have demonstrated that CD4+ T cell EVs enhance B cell responses and serve as a novel immunomodulator to promote antigen‐specific humoral immune responses., CD4+ T cells release bioactive extracellular vesicles. CD4+ T cells extracellular vesicles (EVs) can enhance B cell responses by CD40 ligand (CD40L), which significantly promote B cell activation, proliferation, and antibody production in vitro. In addition, the application of CD4+ T cell EVs further promotes antigen‐specific humoral immune responses in Hepatitis B surface antigen (HBsAg)‐immunized mice.
- Published
- 2018
45. Inhibition of Bruton's tyrosine kinase interferes with pathogenic B-cell development in inflammatory CNS demyelinating disease
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Roxanne Pretzsch, Philipp Haselmayer, Ursula Boschert, Roland Grenningloh, Martin S. Weber, Darius Häusler, Wolfgang Brück, and Sebastian Torke
- Subjects
Encephalomyelitis, Autoimmune, Experimental ,T-Lymphocytes ,Lymphocyte Activation ,Pathology and Forensic Medicine ,Multiple sclerosis ,Cellular and Molecular Neuroscience ,Mice ,Immune system ,Piperidines ,Bruton’s tyrosine kinase ,medicine ,Agammaglobulinaemia Tyrosine Kinase ,Evobrutinib ,Bruton's tyrosine kinase ,Animals ,Humans ,Protein Kinase Inhibitors ,B cell ,chemistry.chemical_classification ,B-Lymphocytes ,Original Paper ,B cells ,Experimental autoimmune encephalomyelitis ,biology ,BTKi ,Cell Differentiation ,medicine.disease ,CNS DEMYELINATING DISEASE ,Mice, Inbred C57BL ,Enzyme ,medicine.anatomical_structure ,Pyrimidines ,chemistry ,Myeloid cells ,biology.protein ,Cancer research ,Neurology (clinical) ,Tyrosine kinase - Abstract
Anti-CD20-mediated B-cell depletion effectively reduces acute multiple sclerosis (MS) flares. Recent data shows that antibody-mediated extinction of B cells as a lasting immune suppression, harbors the risk of developing humoral deficiencies over time. Accordingly, more selective, durable and reversible B-cell-directed MS therapies are needed. We here tested inhibition of Bruton’s tyrosine kinase (BTK), an enzyme centrally involved in B-cell receptor signaling, as the most promising approach in this direction. Using mouse models of MS, we determined that evobrutinib, the first BTK inhibiting molecule being developed, dose-dependently inhibited antigen-triggered activation and maturation of B cells as well as their release of pro-inflammatory cytokines. Most importantly, evobrutinib treatment functionally impaired the capacity of B cells to act as antigen-presenting cells for the development of encephalitogenic T cells, resulting in a significantly reduced disease severity in mice. In contrast to anti-CD20, BTK inhibition silenced this key property of B cells in MS without impairing their frequency or functional integrity. In conjunction with a recent phase II trial reporting that evobrutinib is safe and effective in MS, our mechanistic data highlight therapeutic BTK inhibition as a landmark towards selectively interfering with MS-driving B-cell properties. Electronic supplementary material The online version of this article (10.1007/s00401-020-02204-z) contains supplementary material, which is available to authorized users.
- Published
- 2020
46. SopB activates the Akt-YAP pathway to promote Salmonella survival within B cells
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Araceli Perez-Lopez, Porfirio Nava, Carlos Samuel Galán-Enríquez, Celia Alpuche-Aranda, Vianney Ortiz-Navarrete, and Abraham García-Gil
- Subjects
0301 basic medicine ,Inflammasomes ,Interleukin-1beta ,Cell Cycle Proteins ,Mice ,Phosphatidylinositol 3-Kinases ,0302 clinical medicine ,Salmonella ,NLRC4 ,Phosphorylation ,B-Lymphocytes ,Mice, Inbred BALB C ,Effector ,Pyroptosis ,Inflammasome ,SopB ,Cell biology ,Infectious Diseases ,IL-1β ,030220 oncology & carcinogenesis ,YAP ,Research Paper ,Signal Transduction ,medicine.drug ,Microbiology (medical) ,Immunology ,Down-Regulation ,Biology ,Microbiology ,lcsh:Infectious and parasitic diseases ,03 medical and health sciences ,Bacterial Proteins ,medicine ,Animals ,lcsh:RC109-216 ,Protein kinase B ,PI3K/AKT/mTOR pathway ,Adaptor Proteins, Signal Transducing ,B cells ,Microbial Viability ,Akt ,Calcium-Binding Proteins ,YAP-Signaling Proteins ,Phosphoproteins ,Mice, Inbred C57BL ,030104 developmental biology ,Parasitology ,Apoptosis Regulatory Proteins ,Proto-Oncogene Proteins c-akt ,Inflammasome complex - Abstract
B cells are a target of Salmonella infection, allowing bacteria survival without inducing pyroptosis. This event is due to downregulation of Nlrc4 expression and lack of inflammasome complex activation, which impairs the secretion of IL-1β. YAP phosphorylation is required for downregulation of Nlrc4 in B cells during Salmonella infection; however, the microorganism’s mechanisms underlying the inhibition of the NLRC4 inflammasome in B cells are not fully understood. Our findings demonstrate that the Salmonella effector SopB triggers a signaling cascade involving PI3K, PDK1 and mTORC2 that activates Akt with consequent phosphorylation of YAP. When we deleted sopB in Salmonella, infected B cells that lack Rictor, or inhibited the signaling cascade using a pharmacological approach, we were able to restore the function of the NLRC4 inflammasome in B cells and the ability to control the infection. Furthermore, B cells from infected mice exhibited activation of Akt and YAP phosphorylation, suggesting that Salmonella also triggers this pathway in vivo. In summary, our data demonstrate that the Salmonella effector inositide phosphate phosphatase SopB triggers the PI3K-Akt-YAP pathway to inhibit the NLRC4 inflammasome in B cells. This study provides further evidence that Salmonella triggers cellular mechanisms in B lymphocytes to manipulate the host environment by turning it into a survival niche to establish a successful infection.
- Published
- 2018
47. BAFF and APRIL expression as an autoimmune signature of membranous nephropathy
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Jooyoung Kim, Chun Soo Lim, Hajeong Lee, Sang-Ho Lee, Kwon Wook Joo, Dong Ki Kim, Seung Hee Yang, Hyung Ah Jo, Yon Su Kim, Minkyoung Park, Seung Seok Han, Yun Jung Oh, and Jung Pyo Lee
- Subjects
0301 basic medicine ,medicine.medical_specialty ,030204 cardiovascular system & hematology ,medicine.disease_cause ,Gastroenterology ,Autoimmunity ,Pathogenesis ,03 medical and health sciences ,0302 clinical medicine ,Membranous nephropathy ,Internal medicine ,Biopsy ,medicine ,APRIL ,B-cell activating factor ,Autoimmune disease ,Kidney ,B cells ,Systemic lupus erythematosus ,medicine.diagnostic_test ,business.industry ,autoimmunity ,membranous nephropathy ,medicine.disease ,030104 developmental biology ,medicine.anatomical_structure ,Oncology ,BAFF ,business ,Research Paper - Abstract
// Seung Seok Han 1, 2 , Seung Hee Yang 2 , Hyung Ah Jo 1 , Yun Jung Oh 2 , Minkyoung Park 2 , Joo Young Kim 2 , Hajeong Lee 1, 2 , Jung Pyo Lee 1, 2, 3 , Sang-Ho Lee 4 , Kwon Wook Joo 1, 2 , Chun Soo Lim 1, 3 , Yon Su Kim 1, 2 and Dong Ki Kim 1, 2 1 Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea 2 Kidney Research Institute, Seoul National University, Seoul, Korea 3 Department of Internal Medicine, Seoul National University Boramae Medical Center, Seoul, Korea 4 Department of Internal Medicine, College of medicine, Kyung Hee University, Seoul, Korea Correspondence to: Dong Ki Kim, email: dkkim73@gmail.com Keywords: APRIL; autoimmunity; BAFF; B cells; membranous nephropathy Received: July 03, 2017 Accepted: November 14, 2017 Published: December 14, 2017 ABSTRACT Background: Based on the fact that B-cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL) have a regulatory role in B cell biology, excessive levels of these cytokines can promote autoimmune pathogenesis. However, the expression and implication remain unresolved in cases of membranous nephropathy (MN). Results: The plasma BAFF levels of the primary MN patients were higher than those of healthy controls but lower than those of secondary MN patients, whereas the APRIL levels were similar between the MN patients and healthy controls. The BAFF levels were higher in relapse cases, whereas the APRIL levels were higher in the patients who did not experience remission compared with the counterpart patients. The ectopic expression of BAFF and APRIL was observed in the glomeruli or circulating B cells of MN patients, and this high expression trend was similar to that of lupus patients. Conclusions: Expression profile of BAFF and APRIL in MN is similar to that of other autoimmune disease, which affects the kidney outcomes. Methods: Plasma BAFF and APRIL levels were measured upon kidney biopsy in patients with primary ( n = 89) and secondary MN ( n = 13), and the results were compared with the levels in healthy controls ( n = 111). The kidney outcomes (e.g., remission and relapse) were traced for the median of 3 years. Aberrant expression of the cytokines was evaluated in the kidney and circulating B cells using immunohistochemistry and flow cytometry analyses, respectively.
- Published
- 2017
48. Safety and tolerability of inebilizumab (MEDI-551), an anti-CD19 monoclonal antibody, in patients with relapsing forms of multiple sclerosis: Results from a phase 1 randomised, placebo-controlled, escalating intravenous and subcutaneous dose study
- Author
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Kaushik Patra, Soraya Madani, Armando Flor, Gabriela Klodowska-Duda, Mark Agius, Jing Li, Maciej Maciejowski, Eliezer Katz, Andrzej Potemkowski, Gerard Barron, and Jacob Wesley
- Subjects
Adult ,Male ,medicine.drug_class ,intravenous administration ,Pharmacology ,Antibodies, Monoclonal, Humanized ,Monoclonal antibody ,Placebo ,03 medical and health sciences ,Multiple Sclerosis, Relapsing-Remitting ,0302 clinical medicine ,Pharmacokinetics ,pharmacodynamics ,medicine ,Humans ,030212 general & internal medicine ,Pathophysiology of multiple sclerosis ,subcutaneous administration ,B cells ,Dose-Response Relationship, Drug ,business.industry ,Multiple sclerosis ,Middle Aged ,medicine.disease ,Neurology ,Tolerability ,Inebilizumab ,Pharmacodynamics ,Female ,Neurology (clinical) ,business ,Original Research Papers ,pharmacokinetics ,030217 neurology & neurosurgery - Abstract
Background: B cells may be involved in the pathophysiology of multiple sclerosis (MS). Inebilizumab (formerly MEDI-551) binds to and depletes CD19+ B cells. Objectives: To assess safety, tolerability, pharmacokinetics, pharmacodynamics and immunogenicity of inebilizumab in adults with relapsing MS. Methods: This phase 1 trial randomised 28 patients 3:1 (21, inebilizumab; 7, placebo) to inebilizumab (2 intravenous (IV) doses, days 1 and 15: 30, 100 or 600 mg; or single subcutaneous (SC) dose on day 1: 60 or 300 mg) or matching placebo, with follow-up until at least week 24 or return of CD19+ B-cell count to ⩾80 cells/µL. Results: Complete B-cell depletion was observed across all doses. Infusion/injection (grade 1/2) reactions occurred in 6/15 patients receiving inebilizumab IV, 2/5 placebo IV and 1/6 inebilizumab SC. Serious adverse events occurred in three patients receiving inebilizumab: pyrexia, mixed-drug intoxication (unrelated to inebilizumab; resulted in death) and urinary tract infection. Mean number of cumulative new gadolinium-enhancing lesions over 24 weeks was 0.1 with inebilizumab versus 1.3 with placebo; mean numbers of new/newly enlarging T2 lesions were 0.4 and 2.4, respectively. Conclusion: Inebilizumab had an acceptable safety profile in relapsing MS patients and showed a trend in reductions in new/newly enlarging and gadolinium-enhancing lesions.
- Published
- 2017
49. A Fix for Fractures.
- Subjects
BIOPRINTING ,B cells ,CARTILAGE cells ,BONE morphogenetic proteins ,CORD blood ,STEM cell donors - Abstract
The article offers update on bone fracture prevention and treatments for conditions such as osteoporosis. It discusses findings of several research including fracture repair via bone remodeling using osteoclasts, potential of high frequency sound waves to convert bone marrow derived mesenchymal stem cells into bone cells, and a demineralised bone paper biomaterial used to advanced the understanding of bone biology, model disease progression and screen drug responses.
- Published
- 2023
- Full Text
- View/download PDF
50. The star target in SLE: IL-17.
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Yang, Yi, Yan, Chen, Yu, Le, Zhang, Xiuling, Shang, Jingjing, Fan, Jie, Zhang, Rongwei, Ren, Jie, and Duan, Xinwang
- Subjects
INTERLEUKIN-17 ,SYSTEMIC lupus erythematosus ,IMMUNOLOGICAL tolerance ,T cells ,B cells - Abstract
Purpose: The purpose of this review is to discuss the significance of IL-17 in SLE and the potential of IL-17-targeted therapy. Background: Systemic lupus erythematosus (SLE) is an autoimmune disease that can affect many organs and tissues throughout the body. It is characterized by overactive B and T cells and loss of immune tolerance to autoantigens. Interleukin-17 (IL-17) is a cytokine that promotes inflammation and has been implicated in the pathogenesis of several autoimmune diseases as well as inflammatory diseases. In in vitro cellular experiments in lupus susceptible mice or SLE patients, there is substantial evidence that IL-17 is a highly promising therapeutic target. Methods: We searched papers from PubMed database using the search terms, such as interleukin-17, systemic lupus erythematosus, treatment targets, T cells, lupus nephritis, and other relevant terms. Results: We discuss in this paper the molecular mechanisms of IL-17 expression, Th17 cell proliferation, and the relationship between IL-17 and Th17. The significance of IL-17 in SLE and the potential of IL-17-targeted therapy are further discussed in detail. Conclusion: IL-17 has a very high potential for the development as a star target in SLE. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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