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https://www.readbyqxmd.com/read/29458071/b-cells-in-operational-tolerance
#1
REVIEW
M Chesneau, R Danger, J-P Soulillou, S Brouard
Transplantation is currently the therapy of choice for endstage organ failure even though it requires long-term immunossuppresive therapy, with its numerous side effects, for acceptance of the transplanted organ. In rare cases however, patients develop operational tolerance, that is, graft survival without immunosuppression. Studies conducted on these patients reveal genetic, phenotypic, and functional signatures. They provide a better understanding of the immunological mechanisms involved in operational tolerance and define biomarkers that could be used to adapt immunosuppressive treatment to the individual, safely reduce immunosuppression doses, and ideally and safely guide immunosuppression withdrawal...
February 16, 2018: Human Immunology
https://www.readbyqxmd.com/read/29457982/discovery-of-gdc-0853-a-potent-selective-and-non-covalent-bruton-s-tyrosine-kinase-inhibitor-in-early-clinical-development
#2
James J Crawford, Adam R Johnson, Dinah L Misner, Lisa D Belmont, Georgette M Castanedo, Regina Choy, Melis Coraggio, Liming Dong, Charles Eigenbrot, Rebecca Erickson, Nico Ghilardi, Jonathan Hau, Arna Katewa, Pawan Bir Kohli, Wendy Lee, Joseph W Lubach, Brent S McKenzie, Daniel Fred Ortwine, Leah Schutt, Suzanne Tay, Binqing Wei, Karin Reif, Lichuan Liu, Harvey Wong, Wendy B Young
Btk is a non-receptor cytoplasmic tyrosine kinase involved in B-cell and myeloid cell activation, downstream of B-cell and Fcγ receptors, respectively. Pre-clinical studies have indicated that inhibition of Btk activity might offer a potential therapy in autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus. Here we disclose the discovery and pre-clinical characterization of a potent, selective, and non-covalent Btk inhibitor currently in clinical development. GDC-0853 (29) suppresses B cell- and myeloid cell-mediated components of disease, and demonstrates dose-dependent activity in an in vivo rat model of inflammatory arthritis...
February 19, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29456886/heterogenic-transplantation-of-bone-marrow-derived-rhesus-macaque-mesenchymal-stem-cells-ameliorates-liver-fibrosis-induced-by-carbon-tetrachloride-in-mouse
#3
Xufeng Fu, Bin Jiang, Bingrong Zheng, Yaping Yan, Junfeng Wang, Yanchao Duan, Shanshan Li, Li Yan, Hong Wang, Bingbing Chen, Xiongbo Sang, Weizhi Ji, Ren-He Xu, Wei Si
Liver fibrosis is a disease that causes high morbidity and has become a major health problem. Liver fibrosis can lead to the end stage of liver diseases (livercirrhosisand hepatocellularcarcinoma). Currently, liver transplantation is the only effective treatment for end-stage liver disease. However, the shortage of organ donors, high cost of medical surgery, immunological rejection and transplantation complications severely hamper liver transplantation therapy. Mesenchymal stem cells (MSCs) have been regarded as promising cells for clinical applications in stem cell therapy in the treatment of liver diseases due to their unique multipotent differentiation capacity, immunoregulation and paracrine effects...
2018: PeerJ
https://www.readbyqxmd.com/read/29456038/increase-of-natural-killer-cells-in-children-with-liver-transplantation-acquired-food-allergy
#4
F Mori, C Angelucci, A Cianferoni, S Barni, G Indolfi, A Casini, G Mangone, M Materassi, N Pucci, C Azzari, E Novembre
BACKGROUND: Transplantation-acquired food allergies (TAFA) are frequently reported and considered to be caused by immunosuppressive therapy. The aim of this study was to investigate the allergic and immunologic responses in children who had liver or kidney transplantations. METHODS: Twelve children receiving liver transplantations and 10 children receiving kidney transplantations were investigated. All children underwent the allergy work-up and in most of them, lymphocyte screening and serum cytokine measurements were also performed...
February 15, 2018: Allergologia et Immunopathologia
https://www.readbyqxmd.com/read/29455663/targeting-tumour-microenvironment-by-tyrosine-kinase-inhibitor
#5
REVIEW
Hor-Yue Tan, Ning Wang, Wing Lam, Wei Guo, Yibin Feng, Yung-Chi Cheng
Tumour microenvironment (TME) is a key determinant of tumour growth and metastasis. TME could be very different for each type and location of tumour and TME may change constantly during tumour growth. Multiple counterparts in surrounding microenvironment including mesenchymal-, hematopoietic-originated cells as well as non-cellular components affect TME. Thus, therapeutics that can disrupt the tumour-favouring microenvironment should be further explored for cancer therapy. Previous efforts in unravelling the dysregulated mechanisms of TME components has identified numerous protein tyrosine kinases, while its corresponding inhibitors have demonstrated potent modulatory effect on TME...
February 19, 2018: Molecular Cancer
https://www.readbyqxmd.com/read/29454646/alteration-of-ccr6-cd95-cd4-na%C3%A3-ve-t-cells-in-hiv-1-infected-patients-implication-for-clinical-practice
#6
Hong Sun, Wenqing Geng, Hualu Cui, Guoxin Liang, Yajing Fu, Zining Zhang, Yongjun Jiang, Haibo Ding, Junjie Xu, Hong Shang
The profound deficiency of Th17 cells contributes to HIV disease progression. The mechanisms of their perturbation remain unclear. Recently, CCR6+ CD95+ CD4+ naïve T cells (CCR6+ CD95+ CD4+ TNA ), identified as pre-committed Th17 precursors, were recognized as a subpopulation of CD4+ T cells with stem cell properties. Following phenotypical identification, we evaluated their level in patients during chronic HIV infection and following antiretroviral therapy (ART) using flow cytometry. The levels of CCR6+ CD95+ CD4+ TNA were decreased during chronic HIV infection and correlated with CD4+ T cell counts...
February 10, 2018: Cellular Immunology
https://www.readbyqxmd.com/read/29453848/postoperative-recurrence-of-crohn-s-disease-pathophysiology-diagnosis-and-treatment
#7
Antonio Di Sario, Paola Sassaroli, Luigi Daretti, Giulia Annulli, Laura Schiada, Giorgia Falcioni, Emanuele Bendia, Simone Antuono, Antonio Benedetti
BACKGROUND: Up to 80% of Crohn`s disease (CD) patients require at least one surgical intervention in their lifetime and up to 70% of these patients develop postoperative endoscopic recurrence within 1 year. The most important predictors of early postoperative recurrence are represented by smoking, prior intestinal surgery, penetrating disease and perianal location. Genetic factors, gut microbiota structure and immunological alterations may be involved in the pathogenesis of postoperative recurrence of CD, although their specific roles have to be determined yet...
February 16, 2018: Current Pharmaceutical Biotechnology
https://www.readbyqxmd.com/read/29451987/association-of-adiponectin-leptin-ratio-with-carbohydrate-and-lipid-metabolism-parameters-in-hiv-infected-patients-during-antiretroviral-therapy
#8
Catalin Tiliscan, Victoria Arama, Raluca Mihailescu, Daniela Munteanu, Diana Gabriela Iacob, Cristina Popescu, Remulus Catana, Anca Negru, Alina Lobodan, Stefan Sorin Arama
BACKGROUND: Adiponectin and leptin are adipose tissue hormones that regulate important lipid and glucose metabolic pathways. Our objective was to evaluate the interplay of these hormones described by the adiponectin/leptin ratio (ALR) in correlation to lipid and carbohydrate metabolism parameters in nondiabetic HIV-infected patients during antiretroviral therapy (ART). MATERIALS AND METHODS: We enrolled consecutive nondiabetic patients with confirmed HIV infection, undergoing stable ART regimens for at least six months...
February 16, 2018: Endocrine Research
https://www.readbyqxmd.com/read/29451525/-chronic-pancreatitis-new-definition-and-perspectives
#9
Maria Cristina Conti Bellocchi, Nicolò De Pretis, Antonio Amodio, Alessandro Zerbi, Luca Frulloni
Chronic pancreatitis has been considered over the past years as a single disease, alcohol-induced and different from acute pancreatitis, in terms of etiology and prognosis. Actually, the introduction of a new concept of chronic pancreatitis, now considered as a fibroinflammatory process caused by multiple factors (toxic-metabolic, genetic, immunologic, obstructive), allow to better understand the pathogenesis of this complex disease. Furthermore, the discover of peculiar forms of chronic pancreatitis (autoimmune, paraduodenal, associated to gene mutations), different in term of clinical aspects, findings at imaging, prognosis and therapy, radically changed the concept of the disease...
January 2018: Recenti Progressi in Medicina
https://www.readbyqxmd.com/read/29451276/tisagenlecleucel-an-approved-anti-cd19-chimeric-antigen-receptor-t-cell-therapy-for-the-treatment-of-leukemia
#10
Y Liu, X Chen, W Han, Y Zhang
On August 30, 2017, the U.S. Food and Drug Administration (FDA) approved Novartis' tisagenlecleucel (CTL-019, Kymriah), which is a synthetic bioimmune product of anti-CD19 chimeric antigen receptor (CAR) T cells, for the treatment of relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL). This was a milestone in tumor immunology on account of the significant antitumor effect of tisagenlecleucel for the treatment of relapsed/refractory B-ALL patients. Conventional standard therapies for B-ALL have high failure rates, thus developing new therapies is crucial for patients with B-ALL...
November 2017: Drugs of Today
https://www.readbyqxmd.com/read/29448956/immunomodulatory-plasticity-of-mesenchymal-stem-cells-a-potential-key-to-successful-solid-organ-transplantation
#11
REVIEW
Urvashi Kaundal, Upma Bagai, Aruna Rakha
Organ transplantation remains to be a treatment of choice for patients suffering from irreversible organ failure. Immunosuppressive (IS) drugs employed to maintain the allograft have shown excellent short-term graft survival, but, their long-term use could contribute to immunological and non-immunological risk factors, resulting in graft dysfunctionalities. Upcoming IS regimes have highlighted the use of cell-based therapies, which can eliminate the risk of drug-borne toxicities while maintaining efficacy of the treatment...
February 15, 2018: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29448862/filgotinib-for-the-treatment-of-crohn-s-disease
#12
Remi Labetoulle, Stephane Paul, Xavier Roblin
Inflammatory Bowel Diseases, such as Crohn's disease (CD) and Ulcerative Colitis (UC), are widespread diseases (with an estimated 2.2 million Europeans affected), and even populations previously considered 'low risk' (such as Japan and India) are witnessing an increasing incidence. CD is a chronic, progressive immunologically driven disease, with an evolution characterized by succession of periods of progression and remission. New physiopathological pathways are continuously being discovered, the more we understand about how the disease appears and progresses, the more targets become available for the development of novel therapies...
February 15, 2018: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/29448846/are-infectious-diseases-and-microbiology-new-fields-for-thermal-therapy-research
#13
Deniz Gazel, Mehmet Yılmaz
Antimicrobial chemotherapy and surgery are classical methods for treating infectious diseases. However, there is a need for alternative methods to cure infections caused by antibiotic-resistant pathogens, recurrent or chronic infections, and unreachable local infections in which the use of drugs or surgery is anatomically and physically restricted. Several microorganisms are known to be sensitive to mild hyperthermia, and this sensitivity is one of the potential benefits proposed for the host during an episode of fever...
February 15, 2018: International Journal of Hyperthermia
https://www.readbyqxmd.com/read/29446525/laboratory-testing-for-factor-viii-and-ix-inhibitors-in-haemophilia-a-review
#14
REVIEW
C H Miller
Inhibitors are antibodies directed against haemophilia treatment products which interfere with their function. Factor VIII (FVIII) inhibitors in haemophilia A and factor IX (FIX) inhibitors in haemophilia B are significant clinically when they require a change in a patient's treatment regimen. Their persistence may increase morbidity and mortality. Multiple laboratory tests are now available for detecting and understanding inhibitors in haemophilia. Inhibitors are traditionally measured by their interference in clotting or chromogenic factor assays...
February 15, 2018: Haemophilia: the Official Journal of the World Federation of Hemophilia
https://www.readbyqxmd.com/read/29445583/deep-sustained-response-to-daratumumab-monotherapy-associated-with-t-cell-expansion-in-triple-refractory-myeloma
#15
Saad Z Usmani, Imran Khan, Christopher Chiu, David Foureau, Lawrence J Druhan, Katherine Rigby, Tineke Casneuf, A Kate Sasser
Background: Daratumumab, a human CD38 monoclonal antibody that has direct on-tumor and immunomodulatory mechanisms of action, demonstrated clinical benefit as monotherapy or in combination with established regimens in patients with multiple myeloma with one or more prior lines of therapy. Case presentation: A male patient, who was 70 years of age at the time of diagnosis of multiple myeloma in 2011, relapsed after five lines of therapy, including autologous stem cell transplantation...
2018: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/29445452/exploiting-immune-cell-metabolic-machinery-for-functional-hiv-cure-and-the-prevention-of-inflammaging
#16
REVIEW
Clovis S Palmer, Riya Palchaudhuri, Hassan Albargy, Mohamed Abdel-Mohsen, Suzanne M Crowe
An emerging paradigm in immunology suggests that metabolic reprogramming and immune cell activation and functions are intricately linked. Viral infections, such as HIV infection, as well as cancer force immune cells to undergo major metabolic challenges. Cells must divert energy resources in order to mount an effective immune response. However, the fact that immune cells adopt specific metabolic programs to provide host defense against intracellular pathogens and how this metabolic shift impacts immune cell functions and the natural course of diseases have only recently been appreciated...
2018: F1000Research
https://www.readbyqxmd.com/read/29445380/the-role-of-indoleamine-2-3-dioxygenase-in-cancer-development-diagnostics-and-therapy
#17
REVIEW
Lilla Hornyák, Nikoletta Dobos, Gábor Koncz, Zsolt Karányi, Dénes Páll, Zoltán Szabó, Gábor Halmos, Lóránt Székvölgyi
Tumors are composed of abnormally transformed cell types and tissues that differ from normal tissues in their genetic and epigenetic makeup, metabolism, and immunology. Molecular compounds that modulate the immune response against neoplasms offer promising new strategies to combat cancer. Inhibitors targeting the indoleamine-2,3-dioxygenase 1 enzyme (IDO1) represent one of the most potent therapeutic opportunities to inhibit tumor growth. Herein, we assess the biochemical role of IDO1 in tumor metabolism and immune surveillance, and review current diagnostic and therapeutic approaches that are intended to increase the effectiveness of immunotherapies against highly aggressive and difficult-to-treat IDO-expressing cancers...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29445373/tissue-dependent-tumor-microenvironments-and-their-impact-on-immunotherapy-responses
#18
REVIEW
Amanda J Oliver, Peter K H Lau, Ashleigh S Unsworth, Sherene Loi, Phillip K Darcy, Michael H Kershaw, Clare Y Slaney
Recent advances in cancer immunology have led to a better understanding of the role of the tumor microenvironment (TME) in tumor initiation, progression, and metastasis. Tumors can occur at many locations within the body and coevolution between malignant tumor cells and non-malignant cells sculpts the TME at these sites. It has become increasingly clear that there are specific differences of the TMEs at different anatomical locations, and these tissue-specific TMEs regulate tumor growth, determine metastatic progression, and impact on the outcome of therapy responses...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29438774/palliative-effects-of-moringa-olifera-ethanolic-extract-on-hemato-immunologic-impacts-of-melamine-in-rats
#19
Yasmina M Abd-Elhakim, Khlood M El Bohi, Sahar Khalifa Hassan, Shorouk El Sayed, Sabry M Abd-Elmotal
Melamine (MEL) is a widespread food contaminant and adulterant. Moringa olifera is a widely known medicinal plant with various pharmacological properties. Herein, this study aimed to investigate, for the first time, the probable protective or therapeutic role of M. olifera ethanolic extract (MOE) against MEL induced hemato-immune toxic hazards. Fifty Sprague Dawely male rats were orally treated with distilled water, MOE (800 mg/kg bw), MEL (700 mg/kg bw), MOE/MEl or MOE + MEl. Erythrogram and leukogram profiling were evaluated to assess hematological status...
February 10, 2018: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/29437538/leveraging-rational-protein-engineering-to-improve-mrna-therapeutics
#20
Jeremiah D Farelli, Kirtika H Asrani, Cleo Isaacs, Joanna S deBear, Mary R Stahley, Anumeha Shah, Melissa A Lasaro, Christopher J Cheng, Romesh R Subramanian
Messenger RNA (mRNA) is a promising new class of therapeutics that has potential for treatment of diseases in fields such as immunology, oncology, vaccines, and inborn errors of metabolism. mRNA therapy has several advantages over DNA-based gene therapy, including the lack of the need for nuclear import and transcription, as well as limited possibility of genomic integration. One drawback of mRNA therapy, especially in cases such as metabolic disorders where repeated dosing will be necessary, is the relatively short in vivo half-life of mRNA (∼6-12 h)...
February 13, 2018: Nucleic Acid Therapeutics
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