Skip to main content

Aggregator

Increased Risk of Dementia and its Subtypes following Various Forms of Acquired Brain Injury: a Meta-analysis and Systematic Review

4 months ago
In recent years, acquired brain injuries (ABIs) have been implicated in the development and pathogenesis of dementia; however, existing data is conflicting and often lacks precise classifications or comprehensive analyses. This review sought to synthesize available evidence to assess the association between four major ABI types-traumatic brain injury (TBI), cerebral atherosclerosis (AS), intracranial hemorrhage, and ischemic stroke-and risk of subsequent all-cause dementia (ACD) and dementia...
Jacob Thompson

Cardiolipin-mimic lipid nanoparticles without antibody modification delivered senolytic in vivo CAR-T therapy for inflamm-aging

4 months ago
mRNA-based in vivo chimeric antigen receptor (CAR)-T cell engineering offers advantages over ex vivo therapies, including streamlined manufacturing and transient expression. However, current delivery methods require antibody-modified vehicles with manufacturing challenges. In this study, inspired by cardiolipin, we identify cardiolipin-like di-phosphoramide lipids that improve T cell transfection without targeting ligands, both in vitro and in vivo. The T cell-favored tropism is likely due to...
Zihan Zhang

Immuno-metabolic stress responses control longevity from mitochondrial translation inhibition in C. elegans

4 months ago
Perturbing mitochondrial translation represents a conserved longevity intervention, with proteostasis processes proposed to mediate the resulting lifespan extension. Here, we explore whether other mechanisms may contribute to lifespan extension upon mitochondrial translation inhibition. Using multi-omics and functional in vivo screening, we identify the ethylmalonyl-CoA decarboxylase orthologue C32E8.9 in C. elegans as an essential factor for longevity induced by mitochondrial translation...
Iman Man Hu

Immunosenescence accelerates atherosclerosis development in AAV-PCSK9 mouse model

4 months ago
Aging is a dominant risk factor for atherosclerotic cardiovascular disease and is associated with compositional and functional changes in our immune system, called immunosenescence. To gain insights into the impact of immunosenescence on atherosclerosis, we investigated plaque development and the immune landscape in an AAV-PCSK9 mouse model. Young (3 months) and aged (18 months) male C57Bl/6 mice received a single i.v. injection of a recombinant adeno-associated virus encoding murine PCSK9...
Jill de Mol

A genome-wide in vivo CRISPR activation screen identifies BACE1 as a therapeutic vulnerability of lung cancer brain metastasis

4 months ago
Brain metastasis occurs in up to 40% of patients with non-small cell lung cancer (NSCLC). Considerable genomic heterogeneity exists between the primary lung tumor and respective brain metastasis; however, the identity of the genes capable of driving brain metastasis is incompletely understood. Here, we carried out an in vivo genome-wide CRISPR activation screen to identify molecular drivers of brain metastasis from an orthotopic xenograft model derived from a patient with NSCLC. We found that...
Shawn C Chafe

Antibody durability is influenced by interleukin-2 production by undifferentiated memory T helper cells and extensive B cell clonal expansion

4 months ago
SARS-CoV-2-neutralizing antibody titers serve as immune correlates of protection against COVID-19; however, the durability varies among vaccinees. Here, we demonstrate that the durability of vaccine-boosted antibody responses is closely correlated with the pre-booster capacity of spike-reactive CD4^(+) T cells to produce interleukin (IL)-2 and T helper type 2 (Th2) cytokines. IL-2 production by CD4^(+) T cells was also associated with extensive B cell clonal expansion, which preceded the durable...
Masanori Isogawa