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Redox Biology Jun 2021There has been a recent surge of interest in the unique low molecular weight dietary thiol/thione, ergothioneine. This compound can accumulate at high levels in the body...
There has been a recent surge of interest in the unique low molecular weight dietary thiol/thione, ergothioneine. This compound can accumulate at high levels in the body from diet and may play important physiological roles in human health and development, and possibly in prevention and treatment of disease. Blood levels of ergothioneine decline with age and onset of various diseases. Here we highlight recent advances in our knowledge of ergothioneine.
Topics: Antioxidants; Diet; Ergothioneine; Humans
PubMed: 33558182
DOI: 10.1016/j.redox.2021.101868 -
Cell Feb 2024Microglia (MG), the brain-resident macrophages, play major roles in health and disease via a diversity of cellular states. While embryonic MG display a large...
Microglia (MG), the brain-resident macrophages, play major roles in health and disease via a diversity of cellular states. While embryonic MG display a large heterogeneity of cellular distribution and transcriptomic states, their functions remain poorly characterized. Here, we uncovered a role for MG in the maintenance of structural integrity at two fetal cortical boundaries. At these boundaries between structures that grow in distinct directions, embryonic MG accumulate, display a state resembling post-natal axon-tract-associated microglia (ATM) and prevent the progression of microcavities into large cavitary lesions, in part via a mechanism involving the ATM-factor Spp1. MG and Spp1 furthermore contribute to the rapid repair of lesions, collectively highlighting protective functions that preserve the fetal brain from physiological morphogenetic stress and injury. Our study thus highlights key major roles for embryonic MG and Spp1 in maintaining structural integrity during morphogenesis, with major implications for our understanding of MG functions and brain development.
Topics: Axons; Brain; Macrophages; Microglia; Morphogenesis
PubMed: 38309258
DOI: 10.1016/j.cell.2024.01.012 -
Cell Apr 2020Central nervous system (CNS) macrophages comprise microglia and border-associated macrophages (BAMs) residing in the meninges, the choroid plexus, and the perivascular...
Central nervous system (CNS) macrophages comprise microglia and border-associated macrophages (BAMs) residing in the meninges, the choroid plexus, and the perivascular spaces. Most CNS macrophages emerge during development, with the exception of choroid plexus and dural macrophages, which are replaced by monocytes in adulthood. Whether microglia and BAMs share a developmental program or arise from separate lineages remains unknown. Here, we identified two phenotypically, transcriptionally, and locally distinct brain macrophages throughout development, giving rise to either microglia or BAMs. Two macrophage populations were already present in the yolk sac suggesting an early segregation. Fate-mapping models revealed that BAMs mostly derived from early erythro-myeloid progenitors in the yolk sac. The development of microglia was dependent on TGF-β, whereas the genesis of BAMs occurred independently of this cytokine. Collectively, our data show that developing parenchymal and non-parenchymal brain macrophages are separate entities in terms of ontogeny, gene signature, and requirement for TGF-β.
Topics: Animals; Brain; Cell Lineage; Macrophages; Mice; Microglia; Monocytes; Signal Transduction; Transforming Growth Factor beta
PubMed: 32259484
DOI: 10.1016/j.cell.2020.03.021 -
IUCrData Oct 2021The title compound, CHNS, was obtained by the reduction of 2-mercapto-pyrazine (during its crystallization with 2-mercapto-pyrazine and isonicotinic acid -oxide in...
The title compound, CHNS, was obtained by the reduction of 2-mercapto-pyrazine (during its crystallization with 2-mercapto-pyrazine and isonicotinic acid -oxide in ethanol solution. It crystallizes in the monoclinic space group P. In the crystal, the mol-ecules are linked by N-H⋯N and C-H⋯S hydrogen bonds.
PubMed: 36340983
DOI: 10.1107/S2414314621011020 -
Journal of Extracellular Vesicles Mar 2021Cachexia, characterized by loss of skeletal muscle mass and function, is estimated to inflict the majority of patients with oesophageal squamous cell carcinoma (ESCC)...
Cachexia, characterized by loss of skeletal muscle mass and function, is estimated to inflict the majority of patients with oesophageal squamous cell carcinoma (ESCC) and associated with their poor prognosis. However, its underlying mechanisms remain elusive. Here, we developed an ESCC-induced cachexia mouse model using human xenograft ESCC cell lines and found that ESCC-derived extracellular vesicles (EVs) containing prolyl 4-hydroxylase subunit beta (P4HB) induced apoptosis of skeletal muscle cells. We further identified that P4HB promoted apoptotic response through activating ubiquitin-dependent proteolytic pathway and regulated the stability of phosphoglycerate dehydrogenase (PHGDH) and subsequent antiapoptotic protein Bcl-2. Additionally, we proved that the P4HB inhibitor, CCF642, not only rescued apoptosis of muscle cells in vitro, but also prevented body weight loss and muscle wasting in ESCC-induced cachexia mouse model. Overall, these findings demonstrate a novel pathway for ESCC-induced muscle wasting and advocate for the development of P4HB as a potential intervention target for cachexia in patients with ESCC.
Topics: Animals; Apoptosis; Cell Line, Tumor; Disease Models, Animal; Drug Delivery Systems; Esophageal Squamous Cell Carcinoma; Extracellular Vesicles; Humans; Male; Metabolic Networks and Pathways; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Muscular Atrophy; Phosphoglycerate Dehydrogenase; Procollagen-Proline Dioxygenase; Protein Disulfide-Isomerases; Thiazolidines; Thiones
PubMed: 33732415
DOI: 10.1002/jev2.12060 -
IUCrData Jun 2023The study of the oxidation of various proteins necessitates scrutiny of the amino acid sequence. Since me-thio-nine (Met) and tyrosine (Tyr) are easily oxidized,...
The study of the oxidation of various proteins necessitates scrutiny of the amino acid sequence. Since me-thio-nine (Met) and tyrosine (Tyr) are easily oxidized, peptides that contain these amino acids are frequently studied using a variety of oxidation methods, including, but not limited to, pulse radiolysis, electrochemical oxidation, and laser flash photolysis. To date, the oxidation of the Met-Tyr dipeptide is not fully understood. Several investigators have proposed a mechanism of intra-molecular electron transfer between the sulfide radical of Met and the Tyr residue. Our elucidation of the structure and absolute configuration of l-Met-l-Tyr monohydrate, CHNOS·HO (systematic name: (2)-2-{[(2)-2-amino-4-methyl-sulfanyl-butano-yl]amino}-3-(4-hy-droxy-phen-yl)propanoic acid monohydrate) is presented herein and provides information about the zwitterionic nature of the dipeptide. We suspect that the zwitterionic state of the dipeptide and its inter-action within the solvent medium may play a major role in the oxidation of the dipeptide. In the crystal, all the potential donor atoms inter-act strong N-H⋯O, C-H⋯O, O-H⋯S, and O-H⋯O hydrogen bonds.
PubMed: 37936870
DOI: 10.1107/S2414314623005515