The biological activity of chitosans depends on their degree of polymerization (DP) and degree of acetylation (DA). However, information could also be carried by the pattern of acetylation (PA): the sequence of β-1,4-linked glucosamine (deacetylated/D) and -acetylglucosamine (acetylated/A) units. To address this hypothesis, we prepared partially acetylated chitosan oligosaccharides from a chitosan polymer (DA = 35%, DP = 905) using recombinant chitosan hydrolases with distinct substrate and cleavage specificities. The mixtures were separated into fractions DP4-DP12, which were tested for elicitor and priming activities in rice cells. We confirmed that both activities were influenced by DP, but also observed apparent DA-dependent priming activity, with the ADDD+DADD fraction proving remarkably effective. We then compared all four monoacetylated tetramers prepared using different chitin deacetylases and observed significant differences in priming activity. This demonstrates for the first time that PA influences the biological activity of chitosans, which can now be recognized as information-carrying molecules.
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http://dx.doi.org/10.1021/jacs.9b11466 | DOI Listing |
Cell Death Differ
January 2025
Dana Farber Cancer Institute, Boston, MA, USA.
Cellular senescence contributes to a variety of pathologies associated with aging and is implicated as a cellular state in which cancer cells can survive treatment. Reported senolytic drug treatments act through varying molecular mechanisms, but heterogeneous efficacy across the diverse contexts of cellular senescence indicates a need for predictive biomarkers of senolytic activity. Using multi-parametric analyses of commonly reported molecular features of the senescent phenotype, we assayed a variety of models, including malignant and nonmalignant cells, using several triggers of senescence induction and found little univariate predictive power of these traditional senescence markers to identify senolytic drug sensitivity.
View Article and Find Full Text PDFNat Med
January 2025
Department of Medicine-Medical Oncology, University of Colorado Cancer Center, Denver, CO, USA.
Effective targeting of somatic cancer mutations to enhance the efficacy of cancer immunotherapy requires an individualized approach. Autogene cevumeran is a uridine messenger RNA lipoplex-based individualized neoantigen-specific immunotherapy designed from tumor-specific somatic mutation data obtained from tumor tissue of each individual patient to stimulate T cell responses against up to 20 neoantigens. This ongoing phase 1 study evaluated autogene cevumeran as monotherapy (n = 30) and in combination with atezolizumab (n = 183) in pretreated patients with advanced solid tumors.
View Article and Find Full Text PDFNeurosci Lett
January 2025
Department of Neurology, The University of Arizona, Tucson, AZ 85724, USA; Graduate Interdisciplinary Program in Neuroscience, The University of Arizona, Tucson, AZ 85724, USA; Department of Pharmacology, The University of Arizona, Tucson, AZ 85724, USA. Electronic address:
Sub-anesthetic ketamine has been demonstrated to reduce abnormal involuntary movements (AIMs) in preclinical models of L-DOPA-induced dyskinesia (LID) and retrospective Parkinson's disease (PD) case reports. In this study, we examined the effects on LID of two different statins alone and in combination with ketamine in unilateral 6-hydroxydopamine-lesioned male rats, the standard model for preclinical LID studies. Ketamine attenuated the development of AIMs, while the non-polar lovastatin only showed anti-dyskinetic activity early in the priming period but did not prevent the development of LID, and the polar pravastatin showed no anti-dyskinetic activity.
View Article and Find Full Text PDFCancer Immunol Res
January 2025
Light Chain Bioscience - Novimmune SA, Geneva, Switzerland.
Despite advances in cancer immunotherapy, such as targeting the PD-1/PD-L1 axis, a substantial number of patients harbor tumors that are resistant or relapse. Selective engagement of T-cell co-stimulatory molecules with bispecific antibodies may offer novel therapeutic options by enhancing signal 1-driven activation occurring via T-cell receptor engagement. In this study, we report the development and preclinical characterization of NI-3201, a PD-L1×CD28 bispecific antibody generated on the κλ-body platform that was designed to promote T-cell activity and antitumor function through a dual mechanism of action.
View Article and Find Full Text PDFiScience
December 2024
CIISA - Centro de Investigação Interdisciplinar em Sanidade Animal, Faculdade de Medicina Veterinária, Universidade de Lisboa, 1300-477 Lisboa, Portugal.
Activated CD4 T cells located at mucosal surfaces orchestrate local effector immune mechanisms. When properly polarized, these cells contribute to block infections at early stages and may be essential to restrain the local growth of mucosal tumors, playing a critical role in host protection. How CD4 T cells simultaneously integrate gut-homing instructions and Th polarization signals transmitted by TLR activated dendritic cells (DCs) is unknown.
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