Illuminating the cross-talk between tumor metabolism and immunity in I... Current Opinion in Biotechnology, 2021
The exciting review of Leca et al. (2021) summarizes the role of the Krebs cycle key enzyme IDH in the cross-talk between tumor metabolism and immunity in IDH-mutated cancers and shades light on its relevance in immunotherapeutic approaches of IDH-mutant cancers. Background: IDH is of central importance for the energy metabolism of the cell. IDH1 and 2 are mutated in numerous cancers and lead to the accumulation of the "oncometabolite" 2-hydroxyglutarate (2-HG), which directly influences tumor metabolism and "...
Establishing models of corticosteroid patterns during the life history... General and Comparative Endocrinology, 2021
Like humans, marine mammals can get stressed out, and accurate stress measurement in wildlife is fundamental to understanding how animals cope with and respond to perturbations in their environment. For killer whales (Orcnius orca), environmental contamination and other anthropogenic stressors, such as vessel disturbance and fisheries, are major stressors. To better understand the stress level of whales, researchers use
Human umbilical cord-derived mesenchymal stem cell therapy in patients... Signal Transduct Target Ther., 2020
Abstract No effective drug treatments are available for coronavirus disease 2019 (COVID-19). Host-directed therapies targeting the underlying aberrant immune responses leading to pulmonary tissue damage, death, or long-term functional disability in survivors require clinical evaluation. We performed a parallel assigned controlled, non-randomized, phase 1 clinical trial to evaluate the safety of human umbilical cord-derived mesenchymal stem cells (UC-MSCs) infusions in the treatment of patients with moderate and severe COVID-19 pulmonary di...
Cytomegalovirus promotes murine glioblastoma growth via pericyte recru... The Journal of Clinical Investigation, 2019
Abstract Cytomegalovirus (CMV) has been implicated in glioblastoma (GBM); however, a mechanistic connection in vivo has not been established. The purpose of this study is to characterize the effects of murine CMV (MCMV) on GBM growth in murine models. Syngeneic GBM models were established in mice perinatally infected with MCMV. We found that tumor growth was markedly enhanced in MCMV+ mice, with a significant reduction in overall survival compared with that of controls (P < 0.001). We observed increased angiogenesis and tumor blood flow...
Patrolling Alveolar Macrophages Conceal Bacteria from the Immune Syste... Cell, 2020
Abstract During respiration, humans breathe in more than 10,000 liters of non-sterile air daily, allowing some pathogens access to alveoli. Interestingly, alveoli outnumber alveolar macrophages (AMs), which favors alveoli devoid of AMs. If AMs, like most tissue macrophages, are sessile, then this numerical advantage would be exploited by pathogens unless neutrophils from the blood stream intervened. However, this would translate to omnipresent persistent inflammation. Developing in vivo real-time intravital imaging of alveoli...
Neuropathology of patients with COVID-19 in Germany: a post-mortem cas... The Lancet, 2020
Prominent clinical symptoms of COVID-19 include CNS manifestations. However, it is unclear whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, gains access to the CNS and whether it causes neuropathological changes. Here, Matschke et al. investigated the brain tissue of patients who died from COVID-19 for glial responses, inflammatory changes, and the presence of SARS-CoV-2 in the CNS. The group detected fresh territorial ischaemic lesions in six (14%) patients. 37 (86%) patients had astrogliosis in a...
Coupling of bone resorption and formation by RANKL reverse signalling Nature, 2018
Receptor activator of nuclear factor-kappa B (RANK) ligand (RANKL) binds RANK on the surface of osteoclast precursors to trigger osteoclastogenesis. Recent studies have indicated that osteocytic RANKL has an important role in osteoclastogenesis during bone remodelling; however, the role of osteoblastic RANKL remains unclear. Here we show that vesicular RANK, which is secreted from the maturing osteoclasts, binds osteoblastic RANKL and promotes bone formation by triggering RANKL reverse signalling, which activates Runt-related transcription factor 2 (R...
Transcorneal Electrical Stimulation Reduces Neurodegenerative Process... Annals of Biomedical Engineering, 2020
Abstract Glaucoma is a neurodegenerative disease in which the retinal ganglion cell axons of the optic nerve degenerate concomitant with synaptic changes in the retina, leading finally to death of the retinal ganglion cells (RGCs). Electrical stimulation has been used to improve neural regeneration in a variety of systems, including in diseases of the retina. Therefore, the focus of this study was to investigate whether transcorneal electrical stimulation (TES) in the DBA2/J mouse model of glaucoma could improve retinal or optic nerve path...
Generation of a Broadly Useful Model for COVID-19 Pathogenesis, Vaccin... Cell, 2020
Summary COVID-19, caused by SARS-CoV-2, is a virulent pneumonia, with >4,000,000 confirmed cases worldwide and >290,000 deaths as of May 15, 2020. It is critical that vaccines and therapeutics be developed very rapidly. Mice, the ideal animal for assessing such interventions, are resistant to SARS-CoV-2. Here, we overcome this difficulty by exogenous delivery of human ACE2 with a replication-deficient adenovirus (Ad5-hACE2). Ad5-hACE2-sensitized mice developed pneumonia characterized by weight loss, severe pulmonary pathology, and hi...
IL26 modulates cytokine response and anti-TNF consumption in Crohn's d... J Mol Med (Berl), 2017
Abstract Interleukin IL26 supports killing of microbes and the innate sensing of bacterial-derived DNA (bactDNA). We evaluated the relationship between IL26 serum levels and bactDNA translocation in Crohn's disease (CD). We ran a prospective study on CD patients in remission. IL26 common polymorphisms, serum cytokines and complement protein, amplified-bactDNA, and anti-TNF-α were evaluated. In vitro PBMC analysis was performed. Three hundred and thirteen patients were included (mean CDAI: 83.6 ± 32.8; mean fecal calprotect...