As a member of the tumor necrosis factor (TNF) superfamily, the B-cell activating factor (BAFF) plays a crucial role in B-cell survival and differentiation. Overexpression of this protein has been closely linked to autoimmune disorders and some B-cell malignancies. Using monoclonal antibodies (mAbs) against the BAFF soluble domain appears to be a complementary treatment for some of these diseases. This study aimed to produce and develop a specific Nanobody (Nb), a variable camelid antibody domain, against the soluble domain of BAFF protein. After camel immunization with recombinant protein and preparing cDNA from total RNAs separated from camel lymphocytes, an Nb library was developed. Individual colonies capable of binding selectively to rBAFF were obtained by periplasmic-ELISA, sequenced, and expressed in a bacterial expression system. The specificity and affinity of selected Nb were determined and its target identification and functionality were evaluated using flow cytometry.
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http://dx.doi.org/10.1007/s12033-023-00700-7 | DOI Listing |
Mol Divers
January 2025
Department of Biotechnology, Deen Dayal, Upadhyay Gorakhpur University, Gorakhpur, India.
Chronic lymphocytic leukemia (CLL) is a malignancy caused by the overexpression of the anti-apoptotic protein B-cell lymphoma-2 (BCL-2), making it a critical therapeutic target. This study integrates computational screening, molecular docking, and molecular dynamics to identify and validate novel BCL-2 inhibitors from the ChEMBL database. Starting with 836 BCL-2 inhibitors, we performed ADME and Lipinski's Rule of Five (RO5) filtering, clustering, maximum common substructure (MCS) analysis, and machine learning models (Random Forest, SVM, and ANN), yielding a refined set of 124 compounds.
View Article and Find Full Text PDFJ Neuroinflammation
January 2025
Department of Neuroscience and Experimental Therapeutics, School of Medicine, Texas A&M Health Science Center, Bryan, TX, 77807-3260, USA.
Background: Disturbances of the sleep-wake cycle and other circadian rhythms typically precede the age-related deficits in learning and memory, suggesting that these alterations in circadian timekeeping may contribute to the progressive cognitive decline during aging. The present study examined the role of immune cell activation and inflammation in the link between circadian rhythm dysregulation and cognitive impairment in aging.
Methods: C57Bl/6J mice were exposed to shifted light-dark (LD) cycles (12 h advance/5d) during early adulthood (from ≈ 4-6mo) or continuously to a "fixed" LD12:12 schedule.
Sci Rep
January 2025
Institute of Biomedicine and MediCity Research Laboratories, University of Turku, Turku, Finland.
CD19-Cre is an important and widely used Cre-lox model for B cell-specific genetic manipulation in murine systems. Mice carrying one allele of CD19-Cre are, at the same time, rendered heterozygote for CD19, a crucial coreceptor of the B cell antigen receptor (BCR). As a result, CD19-Cre mice exhibit diminished expression levels of CD19, with potential, yet insufficiently examined, consequences in B cell activation.
View Article and Find Full Text PDFClin Transl Med
January 2025
Department of Neurology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
Background: Anti-N-methyl-D-aspartate receptor encephalitis (anti-NMDARE) is a prevalent type of autoimmune encephalitis caused by antibodies targeting the NMDAR's GluN1 subunit. While significant progress has been made in elucidating the pathophysiology of autoimmune diseases, the immunological mechanisms underlying anti-NMDARE remain elusive. This study aimed to characterize immune cell interactions and dysregulation in anti-NMDARE by leveraging single-cell multi-omics sequencing technologies.
View Article and Find Full Text PDFN Engl J Med
January 2025
From Tel Aviv Sourasky Medical Center (Y.C.C., I.A.), and the Faculty of Medical and Health Sciences, Tel Aviv University (Y.C.C., H.M., I.A.), Tel Aviv, Chaim Sheba Medical Center, Ramat Gan (H.M.), and Hadassah Hebrew University Medical Center, Jerusalem (M.G.) - all in Israel; McGill University and McGill University Health Centre, Montreal (M.S.), and Alberta Health Services, Edmonton (M.P.C.) - all in Canada; Samsung Medical Center, Sungkyunkwan University School of Medicine (K.K.), Seoul St. Mary's Hospital, Catholic University of Korea (C.-K.M.), and Seoul National University College of Medicine (S.-S.Y.) - all in Seoul, South Korea; Hospital Universitario Marqués de Valdecilla, Instituto de Investigación Sanitaria Valdecilla, Universidad de Cantabria, Santander (E.M.O.), Cancer Center Clínica Universidad de Navarra, Center for Applied Medical Research, Pamplona (P.R.-O.), Institut Català d'Oncologia, Josep Carreras Leukemia Research Institute, and the Hospital Germans Trias i Pujol, Barcelona (A.O.), START Madrid-Fundación Jiménez Díaz Early Phase Unit, University Hospital Fundación Jiménez Díaz, Madrid (D.M.), and the University Hospital of Salamanca, Institute for Biomedical Research of Salamanca, the Salamanca Cancer Research Center, and Centro de Investígación Biomédica en Red Cáncer, Salamanca (M.-V.M.) - all in Spain; Janssen Research and Development, Spring House, PA (N.A.Q.C., A.K., M.K., M.R.P., E.S., B.H., J.V., A.B.); and Janssen Research and Development, Allschwil, Switzerland (L.D.S.).
Background: Talquetamab (anti-G protein-coupled receptor family C group 5 member D) and teclistamab (anti-B-cell maturation antigen) are bispecific antibodies that activate T cells by targeting CD3 and that have been approved for the treatment of triple-class-exposed relapsed or refractory multiple myeloma.
Methods: We conducted a phase 1b-2 study of talquetamab plus teclistamab in patients with relapsed or refractory multiple myeloma. In phase 1, we investigated five dose levels in a dose-escalation study.
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