A5100737674- Systemic Lupus Erythematosus Research
- interferon and immune responses
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Congenital heart defects research
- Developmental Biology and Gene Regulation
- Atherosclerosis and Cardiovascular Diseases
- Automotive and Human Injury Biomechanics
- DNA Repair Mechanisms
- Cytokine Signaling Pathways and Interactions
- Cancer-related Molecular Pathways
- Inflammasome and immune disorders
- Cell death mechanisms and regulation
- Ubiquitin and proteasome pathways
- Mathematical and Theoretical Epidemiology and Ecology Models
- Epigenetics and DNA Methylation
- RNA Interference and Gene Delivery
- Monoclonal and Polyclonal Antibodies Research
- Cancer Mechanisms and Therapy
- Evolution and Genetic Dynamics
- Immune cells in cancer
- T-cell and B-cell Immunology
- Genetics and Neurodevelopmental Disorders
- Chromatin Remodeling and Cancer
- Blood disorders and treatments
- Transportation Safety and Impact Analysis
Tsinghua University
2022-2025
National Institutes of Health
2019-2024
North Sichuan Medical University
2024
Northwest A&F University
2024
Huntsman Cancer Institute
2007-2023
University of Utah
2007-2023
National Institute of Arthritis and Musculoskeletal and Skin Diseases
2019-2023
University of Michigan
2023
University of Chinese Academy of Sciences
2023
Institute of Genetics and Developmental Biology
2023
Mitochondrial stress releases mitochondrial DNA (mtDNA) into the cytosol, thereby triggering type Ι interferon (IFN) response. outer membrane permeabilization, which is required for mtDNA release, has been extensively studied in apoptotic cells, but little known about its role live cells. We found that oxidatively stressed mitochondria release short fragments via pores formed by voltage-dependent anion channel (VDAC) oligomers membrane. Furthermore, positively charged residues N-terminal...
Neutrophil dysregulation is implicated in the pathogenesis of systemic lupus erythematosus (SLE). SLE characterized by elevated levels a pathogenic neutrophil subset known as low-density granulocytes (LDGs). The origin and phenotypic, functional, heterogeneity LDGs remain to be systematically determined. Transcriptomics epigenetic assessment LDGs, autologous normal-density neutrophils, healthy control neutrophils was performed bulk single-cell RNA sequencing assay for transposase-accessible...
Abstract Increased risk of premature cardiovascular disease (CVD) is well recognized in systemic lupus erythematosus (SLE). Aberrant type I-Interferon (IFN)-neutrophil interactions contribute to this enhanced CVD risk. In animal models, the Janus kinase (JAK) inhibitor tofacitinib improves clinical features, immune dysregulation and vascular dysfunction. We conducted a randomized, double-blind, placebo-controlled trial SLE subjects (ClinicalTrials.gov NCT02535689). study, 30 are randomized...
HER2 belongs to the human epidermal growth factor receptor tyrosine kinase family. Its overexpression or hyperactivation is a leading cause for multiple types of cancers. functions mainly through dimerization with other family members, such as EGFR. However, molecular details heterodimer assembly have not been completely understood. Here, we report cryo-EM structures EGF- and epiregulin-bound EGFR/HER2 ectodomain complexes at resolutions 3.3 Å 4.5 Å, respectively. Together functional...
Neutrophil infiltration into the synovial joint is a hallmark of rheumatoid arthritis (RA), disease characterised by progressive bone erosion. However, mechanisms which neutrophils participate in destruction remain unclear. Carbamylation posttranslational modification linked to increased erosion RA and we previously showed that carbamylation present neutrophil extracellular traps (NETs). it remains unclear whether NETs their carbamylated protein cargo directly promote alter osteoclast biology.
Significance Despite clear differences in female and male immunity that may contribute to variations response infections predisposition cancer autoimmunity, the exact mechanisms drive this stark contrast remain insufficiently characterized. Neutrophils play essential roles homeostasis disease, but little is known about how sex modulate their phenotype function. Using transcriptomic functional approaches, we report healthy young adult females have an activated/mature neutrophil profile...
Type III IFN lambdas (IFN-λ) have recently been described as important mediators of immune responses at barrier surfaces. However, their role in autoimmune diseases such systemic lupus erythematosus (SLE), a condition characterized by aberrant type I signaling, has not determined. Here, we identify nonredundant for IFN-λ dysregulation and tissue inflammation model TLR7-induced lupus. protein is increased murine receptor (Ifnlr1) deficiency significantly reduces cell activation associated...
A role for mitochondrial dysfunction has been proposed in the immune dysregulation and organ damage characteristic of systemic lupus erythematosus (SLE). Idebenone is a coenzyme Q10 synthetic quinone analog an antioxidant that used humans to treat diverse diseases which function impaired. This study was undertaken assess whether idebenone ameliorates murine models.Idebenone administered orally MRL/lpr mice at 2 different doses (1 gm/kg or 1.5 idebenone-containing diet) 8 weeks. At peak...
Neutrophil dysregulation and the type I interferon (IFN) axis have been proposed to contribute premature cardiovascular disease, a leading cause of mortality in patients with systemic lupus erythematosus (SLE). In present study, we evaluated ability anifrolumab, IFN receptor-blocking antibody, reduce neutrophil extracellular trap (NET) formation modulate cardiometabolic disease markers comparison placebo.
Axin negatively regulates the Wnt pathway during axis formation and plays a central role in cell growth control tumorigenesis. We found that also serves as scaffold protein for mitogen-activated kinase activation further determined structural requirement this activation. Overexpression of 293T cells leads to differential kinases, with robust induction c-Jun NH(2)-terminal (JNK)/stress-activated kinase, moderate p38, negligible extracellular signal-regulated kinase. forms complex MEKK1...
Abstract Daxx, a death domain–associated protein, has been implicated in proapoptosis, antiapoptosis, and transcriptional regulation. Many factors known to play critically important roles controlling apoptosis gene transcription have shown associate with including the Ser/Thr protein kinase HIPK2, promyelocytic leukemia histone deacetylases, chromatin remodeling ATRX. Although it is clear that Daxx may exert multiple functions, underlying mechanisms remain far from clear. Here, we show Axin,...
Xenobiotic and host active substances interact with gut microbiota to influence human health therapeutics. Dietary, pharmaceutical, herbal environmental are modified by altered bioavailabilities, bioactivities toxic effects. Xenobiotics also affect implications. Knowledge of these substance interactions is important for understanding microbiota-regulated functions Established databases provide useful information about the microbiota-disease associations, diet drug interventions, modulation...
Neutrophil extracellular traps (NETs) are lattices composed of nucleic material bound to neutrophil granule proteins. NETs may play pathogenic roles in the development and severity autoimmune diseases such as systemic lupus erythematosus (SLE), at least part, through induction type I interferon (IFN) responses via externalization oxidized immunostimulatory DNA. A distinct subset SLE proinflammatory neutrophils (low-density granulocytes [LDGs]) displays enhanced ability form that damage...
Itaconic acid, a Krebs cycle-derived immunometabolite, is synthesized by myeloid cells in response to danger signals control inflammasome activation, type I interferon (IFN) responses, and oxidative stress. As these pathways are dysregulated systemic lupus erythematosus (SLE), we investigated the role of an itaconic acid derivative treatment established murine lupus.
<title>Abstract</title> Metamaterials with compression-torsion or buckling mechanism have demonstrated significant potential for energy absorption through the efficient material utilization. However, metamaterials easily trigger deformation, resulting in low load-bearing capacity, and ones high peak load but fluctuations, accompanying severe localized deformations. Here, we propose chiral multi-curved shell (CMCS) that synergistically couple mechanisms, achieving smooth curves maximizing...
Tumor suppressor p53 prevents cell transformation by inducing apoptosis and other responses. Homozygous TP53 deletion occurs in various types of human cancers for which no therapeutic strategies have yet been reported. TCGA database analysis shows that the homozygous locus mostly exhibits co-deletion neighboring gene FXR2, belongs to Fragile X family. Here, we demonstrate inhibition remaining family member FXR1 selectively blocks proliferation cancer cells containing both FXR2 a collateral...
Objective Gasdermin D (GSDMD) is the key executioner of an inflammatory cell death mechanism known as pyroptosis. Recent reports have also implicated GSDMD in other mechanisms death, including apoptosis, necroptosis, and NETosis. Given role dysregulated autoimmune syndromes such systemic lupus erythematosus (SLE), this study was undertaken a murine model to investigate whether plays pathogenic autoimmunity by promoting leading increased generation nuclear autoantigens autoantibodies. Methods...
Premature cardiovascular events in systemic lupus erythematosus (SLE) contribute to morbidity and mortality, with no effective preventive strategies described date. Immune dysregulation metabolic disturbances appear play prominent roles the induction of vascular disease SLE. The peroxisome proliferator activated receptor-gamma agonist pioglitazone (PGZ suppresses damage immune murine improves endothelial dysfunction other inflammatory diseases. We hypothesised that PGZ could improve...
Chronic alcohol users often exhibit an increased minimum alveolar concentration (MAC) of sevoflurane, yet the specific mechanism remains unclear. It has been reported that ethanol exposure can upregulate protein expression and enzyme activity cytochrome P450 2E1 (CYP2E1). CYP2E1 is a key converts 2-5% sevoflurane into equimolar amounts hexafluoroisopropanol (HFIP) F
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Abstract One of the most highly conserved steps in left–right patterning is asymmetric gene expression lateral plate mesoderm (LPM). Here, we quantitatively describe timing posterior to anterior (PA) wave‐like propagation zebrafish southpaw (Nodal) and pitx2 LPM lefty1 midline. By altering PA wave, provide evidence that wave instructs brain asymmetry. We find initiation midline depends on Southpaw, casanova ( sox32 ) two Nodal inhibitors, charon , have distinct roles upstream initiation....