Result 1 - 10 of total 14839
bioRxiv : the preprint server for biology
2023
Abstract: Group B ...
| Abstract | Group B |
|---|---|
| Language | English |
| Publishing date | 2023-05-24 |
| Publishing country | United States |
| Document type | Preprint |
| DOI | 10.1101/2023.05.24.542094 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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bioRxiv : the preprint server for biology
2024
Abstract: In response to antigens, B cells undergo affinity maturation and class switching mediated ... the molecule essential for T cell tolerance, is expressed in GC B cells in a CD40-dependent manner, interacts ... function. AIRE deficiency in B cells caused altered antibody repertoire, increased somatic hypermutations ...
| Abstract | In response to antigens, B cells undergo affinity maturation and class switching mediated by activation-induced cytidine deaminase (AID) in germinal centers (GCs) of secondary lymphoid organs, but uncontrolled AID activity can precipitate autoimmunity and cancer. The regulation of GC antibody diversification is of fundamental importance but not well understood. We found that autoimmune regulator (AIRE), the molecule essential for T cell tolerance, is expressed in GC B cells in a CD40-dependent manner, interacts with AID and negatively regulates antibody affinity maturation and class switching by inhibiting AID function. AIRE deficiency in B cells caused altered antibody repertoire, increased somatic hypermutations, elevated autoantibodies to T helper 17 effector cytokines and defective control of skin |
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| Language | English |
| Publishing date | 2024-01-12 |
| Publishing country | United States |
| Document type | Preprint |
| DOI | 10.1101/2024.01.10.574926 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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Journal of medicinal chemistry
2024 Volume 67, Issue 2, Page(s) 1500–1512
Abstract: Casitas B-lymphoma proto-oncogene-b (Cbl-b), a member of the Cbl family of RING finger E3 ubiquitin ... studies using gene-targeting approaches have provided direct evidence that Cbl-b negatively regulates T, B ... and NK cell activation via a ubiquitin-mediated protein modulation. Thus, inhibition of Cbl-b ligase ...
| Abstract | Casitas B-lymphoma proto-oncogene-b (Cbl-b), a member of the Cbl family of RING finger E3 ubiquitin ligases, has been demonstrated to play a central role in regulating effector T-cell function. Multiple studies using gene-targeting approaches have provided direct evidence that Cbl-b negatively regulates T, B, and NK cell activation via a ubiquitin-mediated protein modulation. Thus, inhibition of Cbl-b ligase activity can lead to immune activation and has therapeutic potential in immuno-oncology. Herein, we describe the discovery and optimization of an arylpyridone series as Cbl-b inhibitors by structure-based drug discovery to afford compound |
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| MeSH term(s) | Proto-Oncogene Proteins c-cbl/metabolism ; Ubiquitin-Protein Ligases/metabolism ; T-Lymphocytes/metabolism ; Phosphorylation ; Ubiquitin/metabolism |
| Chemical Substances | Proto-Oncogene Proteins c-cbl (EC 2.3.2.27) ; Ubiquitin-Protein Ligases (EC 2.3.2.27) ; Ubiquitin |
| Language | English |
| Publishing date | 2024-01-16 |
| Publishing country | United States |
| Document type | Journal Article |
| ZDB-ID | 218133-2 |
| ISSN | 1520-4804 ; 0022-2623 |
| ISSN (online) | 1520-4804 |
| ISSN | 0022-2623 |
| DOI | 10.1021/acs.jmedchem.3c02083 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
| Zs.B 151: Show issues | Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG) |
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| Zs.MB 1: Show issues |
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Nature reviews. Gastroenterology & hepatology
2023 Volume 20, Issue 2, Page(s) 65
| MeSH term(s) | Humans ; Colon ; Colitis ; Intestinal Mucosa ; Wound Healing |
|---|---|
| Language | English |
| Publishing date | 2023-01-06 |
| Publishing country | England |
| Document type | Journal Article ; Comment |
| ZDB-ID | 2493722-8 |
| ISSN | 1759-5053 ; 1759-5045 |
| ISSN (online) | 1759-5053 |
| ISSN | 1759-5045 |
| DOI | 10.1038/s41575-022-00737-0 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
| Zs.A 6020: Show issues | Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG) |
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| Zs.MG 97: Show issues |
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The Lancet. Infectious diseases
2024
Abstract: Social determinants of health are important in designing effective interventions for hepatitis B ...
| Abstract | Social determinants of health are important in designing effective interventions for hepatitis B virus (HBV) infection. This systematic review characterises equity-oriented, social determinants of health-focused HBV interventions, and describes their effectiveness in terms of the prevention, care, or treatment of HBV in high-income countries. We searched electronic databases for central concepts of 'HBV', 'equity', 'social determinants of health', 'intervention', and 'Organization for Economic Co-operation and Development (OECD) countries'. Screening and data abstraction were conducted independently by two reviewers. Data were abstracted from 66 studies; articles with a comparative study design (n=36) were included in the narrative synthesis, highlighting social determinants of health domains of interventions, HBV-relevant health outcomes, and extra-health social determinants of health effects (ie, those effects that extend beyond health outcomes). Synthesis aligned with six emergent themes corresponding to HBV prevention and care: knowledge and education, diagnosis and screening, immunisation, care initiation, engagement with clinical care and treatment, and upstream prevention. Studies presented a heterogeneous array of HBV-relevant health outcomes. Most interventions were tailored for social determinants of health domains of race, ethnicity, culture, and language; drug use; and socioeconomic status. Across the themes, at least two-thirds of interventions showed comparative effectiveness for addressing HBV. Extra-health social determinants of health outcomes were observed for two studies. Considerable diversity in population-level approaches was observed regarding intervention goals and effectiveness; most interventions were effective at enhancing the prevention, care, or treatment of HBV. |
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| Language | English |
| Publishing date | 2024-01-03 |
| Publishing country | United States |
| Document type | Journal Article ; Review |
| ZDB-ID | 2061641-7 |
| ISSN | 1474-4457 ; 1473-3099 |
| ISSN (online) | 1474-4457 |
| ISSN | 1473-3099 |
| DOI | 10.1016/S1473-3099(23)00590-X |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
| Zs.A 5743: Show issues | Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG) |
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ACS medicinal chemistry letters
2023 Volume 14, Issue 12, Page(s) 1848–1856
Abstract: Casitas B-lineage lymphoma proto-oncogene-b (Cbl-b) is a RING finger E3 ligase that is responsible ... for repressing T-cell, natural killer (NK) cell, and B-cell activation. The robust antitumor activity observed ... in Cbl-b deficient mice arising from elevated T-cell and NK-cell activity justified our discovery effort ...
| Abstract | Casitas B-lineage lymphoma proto-oncogene-b (Cbl-b) is a RING finger E3 ligase that is responsible for repressing T-cell, natural killer (NK) cell, and B-cell activation. The robust antitumor activity observed in Cbl-b deficient mice arising from elevated T-cell and NK-cell activity justified our discovery effort toward Cbl-b inhibitors that might show therapeutic promise in immuno-oncology, where activation of the immune system can drive the recognition and killing of cancer cells. We undertook a high-throughput screening campaign followed by structure-enabled optimization to develop a novel benzodiazepine series of potent Cbl-b inhibitors. This series displayed nanomolar levels of biochemical potency, as well as potent T-cell activation. The functional activity of this class of Cbl-b inhibitors was further corroborated with ubiquitin-based cellular assays. |
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| Language | English |
| Publishing date | 2023-11-17 |
| Publishing country | United States |
| Document type | Journal Article |
| ISSN | 1948-5875 |
| ISSN | 1948-5875 |
| DOI | 10.1021/acsmedchemlett.3c00439 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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ImmunoHorizons
2024 Volume 8, Issue 3, Page(s) 254–268
Abstract: The impact of B cell deficiency on the humoral and cellular responses to SARS-CoV2 mRNA vaccination ... persons with multiple sclerosis on B cell depletion therapy (MS-αCD20) receiving mRNA homologous boosting (n = 36). Pre ... not memory, T cells. The enhancement of CD8 T cells in the setting of B cell depletion suggests ...
| Abstract | The impact of B cell deficiency on the humoral and cellular responses to SARS-CoV2 mRNA vaccination remains a challenging and significant clinical management question. We evaluated vaccine-elicited serological and cellular responses in 1) healthy individuals who were pre-exposed to SARS-CoV-2 (n = 21), 2) healthy individuals who received a homologous booster (mRNA, n = 19; or Novavax, n = 19), and 3) persons with multiple sclerosis on B cell depletion therapy (MS-αCD20) receiving mRNA homologous boosting (n = 36). Pre-exposure increased humoral and CD4 T cellular responses in immunocompetent individuals. Novavax homologous boosting induced a significantly more robust serological response than mRNA boosting. MS-α CD20 had an intact IgA mucosal response and an enhanced CD8 T cell response to mRNA boosting compared with immunocompetent individuals. This enhanced cellular response was characterized by the expansion of only effector, not memory, T cells. The enhancement of CD8 T cells in the setting of B cell depletion suggests a regulatory mechanism between B and CD8 T cell vaccine responses. |
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| MeSH term(s) | Humans ; COVID-19 Vaccines ; Multiple Sclerosis ; RNA, Viral ; COVID-19/prevention & control ; SARS-CoV-2 ; RNA, Messenger |
| Chemical Substances | COVID-19 Vaccines ; RNA, Viral ; RNA, Messenger |
| Language | English |
| Publishing date | 2024-04-05 |
| Publishing country | United States |
| Document type | Journal Article |
| ISSN | 2573-7732 |
| ISSN (online) | 2573-7732 |
| DOI | 10.4049/immunohorizons.2300108 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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2024
Abstract: ... therapy approved for treatment of relapsed/refractory (R/R) large B-cell lymphoma (LBCL). Despite ...
| Abstract | Axicabtagene ciloleucel (axi-cel) is an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy approved for treatment of relapsed/refractory (R/R) large B-cell lymphoma (LBCL). Despite extensive data supporting the use of axi-cel in patients with LBCL, outcomes stratified by race and ethnicity groups are limited. Here, we report clinical outcomes with axi-cel in patients with R/R LBCL by race and ethnicity in both real-world and clinical trial settings. In the real-world setting, 1290 patients with R/R LBCL who received axi-cel between 2017-2020 were identified from the Center for International Blood and Marrow Transplant Research database; 106 and 169 patients were included from the ZUMA-1 and ZUMA-7 clinical trials, respectively. Adjusted odds ratio (OR) and hazard ratio (HR) for race and ethnicity groups are reported. Overall survival was consistent across race/ethnicity groups. However, non-Hispanic (NH) Black patients had lower overall response rate (OR, 0.37, [95% CI, 0.22-0.63]) and lower complete response rate (OR, 0.57, [95% CI, 0.33-0.97]) than NH-white patients. NH-Black patients also had a shorter progression-free survival versus NH-white (HR, 1.41, [95% CI, 1.04-1.90]) and NH-Asian patients (HR, 1.67, [95% CI, 1.08-2.59]). NH-Asian patients had a longer duration of response compared with NH-white (HR, 0.56, [95% CI, 0.33-0.94]) and Hispanic patients (HR, 0.54, [95% CI, 0.30-0.97]). There was no difference in cytokine release syndrome by race/ethnicity; however, higher rates of any-grade ICANS were observed in NH-white patients compared with other patients. These results provide important context when treating patients with R/R LBCL with axi-cel across different racial and ethnic groups. ZUMA-1 (NCT02348216) and ZUMA-7 (NCT03391466), both registered on ClinicalTrials.gov. |
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| Language | English |
| Publishing date | 2024-04-18 |
| Publishing country | United States |
| Document type | Journal Article |
| ZDB-ID | 80069-7 |
| ISSN | 1528-0020 ; 0006-4971 |
| ISSN (online) | 1528-0020 |
| ISSN | 0006-4971 |
| DOI | 10.1182/blood.2023023447 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
| Uh III Zs.140: Show issues | Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG) |
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| Zs.MO 364: Show issues |
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Journal of the American Heart Association
2024 Volume 13, Issue 4, Page(s) e031417
Abstract: ... activated B cells producing agonistic autoantibodies to AT1-AA (angiotensin II type I receptor ... We hypothesize that rituximab, a B cell-depleting chemotherapeutic, will deplete maternal B cells in reduced ... treatment. RUPP offspring also had increased circulating B cells, cytolytic natural killer cells, and ...
| Abstract | Background: Preeclampsia, new-onset hypertension during pregnancy alongside other organ dysfunction, is the leading cause of mortality for the mother and low birth weight for the baby. Low birth weight contributes to high risk of cardiovascular disorders later in life. Women with preeclampsia have activated B cells producing agonistic autoantibodies to AT1-AA (angiotensin II type I receptor). We hypothesize that rituximab, a B cell-depleting chemotherapeutic, will deplete maternal B cells in reduced uterine perfusion pressure (RUPP) rats without worsening the effect of placental ischemia on pup growth and survival. Methods and results: To test this hypothesis, the RUPP procedure was performed, and rituximab was continuously infused via miniosmotic pump. Maternal blood and tissues were collected. A separate group of dams were allowed to deliver, pup weights were recorded, and at 4 months of age, tissues were collected from offspring. Immune cells were measured via flow cytometry, and AT1-AA was quantified using a contraction bioassay. Blood pressure increased in RUPP rats and was normalized with rituximab treatment. RUPP offspring also had increased circulating B cells, cytolytic natural killer cells, and increased circulating AT1-AA, which were normalized with maternal rituximab treatment. This is the first study to analyze the AT1-AA in RUPP offspring, which was normalized with rituximab. Conclusions: Our findings indicate that perinatal rituximab lowers maternal mean arterial pressure in RUPP rats and improves birth weight, circulating AT1-AA, and circulating natural killer cells, indicating that rituximab improves adverse fetal outcomes in response to placental ischemia. |
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| MeSH term(s) | Rats ; Female ; Pregnancy ; Animals ; Humans ; Placenta/blood supply ; Pre-Eclampsia/drug therapy ; Pre-Eclampsia/prevention & control ; Rats, Sprague-Dawley ; Rituximab/pharmacology ; Rituximab/therapeutic use ; Blood Pressure/physiology ; Ischemia ; Receptor, Angiotensin, Type 1 |
| Chemical Substances | Rituximab (4F4X42SYQ6) ; Receptor, Angiotensin, Type 1 |
| Language | English |
| Publishing date | 2024-02-14 |
| Publishing country | England |
| Document type | Journal Article |
| ZDB-ID | 2653953-6 |
| ISSN | 2047-9980 ; 2047-9980 |
| ISSN (online) | 2047-9980 |
| ISSN | 2047-9980 |
| DOI | 10.1161/JAHA.123.031417 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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Canadian liver journal
2024 Volume 7, Issue 1, Page(s) 28–39
Abstract: Background: Migrants from hepatitis B virus (HBV) endemic regions are at high risk of having ...
| Abstract | Background: Migrants from hepatitis B virus (HBV) endemic regions are at high risk of having chronic infection. Despite this, HBV knowledge and awareness programming, and low-barrier screening methods such as point of care (POC) testing, among this group have yet to become routine. Methods: We conducted a mass HBV POC screening and knowledge and awareness campaign for individuals of Chinese descent in Toronto, Canada. POC screening was administered, then participants completed a knowledge questionnaire. Logistic regression identified associations between demographic factors and participants' level of HBV knowledge. Results: From 2015 to 2018, 33 outreach events resulted in 891 individuals completing testing and the knowledge questionnaire. Individuals averaged 64.4 years old. Most, 62% ( Conclusions: Improving knowledge and awareness of HBV is critical to empowering people, especially migrants who experience barriers to care, to pursue vaccination, testing, and treatment. Combining knowledge outreach and POC test campaigns, enabled discussion and screening for HBV with large numbers of people, and can be tailored for optimal effectiveness for specific groups. |
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| Language | English |
| Publishing date | 2024-02-26 |
| Publishing country | Canada |
| Document type | Journal Article |
| ISSN | 2561-4444 |
| ISSN (online) | 2561-4444 |
| DOI | 10.3138/canlivj-2023-0015 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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