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Handberg Wulff posted an update 6 months, 4 weeks ago
Furthermore, a positive correlation between PKM2 and Galectin-9 expression is observed in HNSCC tissues. The induction of Galectin-9 expression by PKM2 can be affected by a lactate transporter inhibitor. Mechanically, lactate impeded the suppressive transcriptional complex formation of NF-κB and histone deacetylase 3 (HDAC3), which released the transcription of Galectin-9 mediated by NF-κB signaling. Our findings demonstrate that lactate produced by PKM2 upregulation promotes tumor progression and Galectin-9-mediated immunosuppression via NF-κB signaling inhibition in HNSCC, which bridges metabolism and immunosuppression. The novel PKM2-lactate-Galectin-9 axis might be a potential therapeutic target in HNSCC.This review covers recent findings in the genomics of obsessive-compulsive disorder (OCD), obsessive-compulsive symptoms, and related traits from a dimensional perspective. We focus on discoveries stemming from technical and methodological advances of the past five years and present a synthesis of human genomics research on OCD. On balance, reviewed studies demonstrate that OCD is a dimensional trait with a highly polygenic architecture and genetic correlations to multiple, often comorbid psychiatric phenotypes. We discuss the phenotypic and genetic findings of these studies in the context of the dimensional framework, relying on a continuous phenotype definition, and contrast these observations with discoveries based on a categorical diagnostic framework, relying on a dichotomous case/control definition. Finally, we highlight gaps in knowledge and new directions for OCD genetics research.Depression and anxiety are common and often comorbid mental health disorders that represent risk factors for aging-related conditions. Brain aging has shown to be more advanced in patients with major depressive disorder (MDD). Here, we extend prior work by investigating multivariate brain aging in patients with MDD, anxiety disorders, or both, and examine which factors contribute to older-appearing brains. Adults aged 18-57 years from the Netherlands Study of Depression and Anxiety underwent structural MRI. A pretrained brain-age prediction model based on >2000 samples from the ENIGMA consortium was applied to obtain brain-predicted age differences (brain PAD, predicted brain age minus chronological age) in 65 controls and 220 patients with current MDD and/or anxiety. Brain-PAD estimates were associated with clinical, somatic, lifestyle, and biological factors. After correcting for antidepressant use, brain PAD was significantly higher in MDD (+2.78 years, Cohen’s d = 0.25, 95% CI -0.10-0.60) and anxiety patients (+2.91 years, Cohen’s d = 0.27, 95% CI -0.08-0.61), compared with controls. There were no significant associations with lifestyle or biological stress systems. A multivariable model indicated unique contributions of higher severity of somatic depression symptoms (b = 4.21 years per unit increase on average sum score) and antidepressant use (-2.53 years) to brain PAD. Advanced brain aging in patients with MDD and anxiety was most strongly associated with somatic depressive symptomatology. We also present clinically relevant evidence for a potential neuroprotective antidepressant effect on the brain-PAD metric that requires follow-up in future research.BACKGROUND Kawasaki disease (KD) is a systemic vasculitis that predominantly occurs in children, but the pathogenesis of KD remains unclear. Here, we explored key genes and underlying mechanisms potentially involved in KD using bioinformatic analyses. MATERIAL AND METHODS The shared differentially expressed genes (DEGs) in KD compared to control samples were identified using the microarray data from the Gene Expression Omnibus Series (GSE) 18606, GSE68004, and GSE73461. Analyses of the functional annotation, protein-protein interaction (PPI) network, microRNA-target DEGs regulatory network, and immune cell infiltration were performed. The expression of hub genes before and after intravenous immunoglobulin (IVIG) treatment in KD was further verified using GSE16797. RESULTS A total of 195 shared DEGs (164 upregulated and 31 downregulated genes) were identified between KD and healthy controls. ARS-1620 price These shared DEGs were mainly enriched in immune and inflammatory responses. Ten upregulated hub genes (ITGAX, SPI1, LILRB2, MMP9, S100A12, C3AR1, RETN, MAPK14, TLR5, MYD88) and the most significant module were identified in the PPI network. There were 309 regulatory relationships detected within 70 predicted microRNAs and 193 target DEGs. The immune cell infiltration analysis showed that monocytes, neutrophils, activated mast cells, and activated natural killer cells had relatively high proportions and were significantly more infiltrated in KD samples. Six hub genes of ITGAX, LILRB2, C3AR1, MAPK14, TLR5, and MYD88 were markedly downregulated after IVIG treatment for KD. CONCLUSIONS Our study identified the candidate genes and associated molecules that may be related to the KD process, and provided new insights into potential mechanisms and therapeutic targets for KD.BACKGROUND West Nile virus (WNv) is the leading cause of epidemic arbovirus encephalitis in the continental United States. Movement disorders (MDs) have been reported in 20% to 40% of patients with WNv and about 37% of patients with WNv encephalitis have changes on magnetic resonance imaging (MRI). We report 2 unusual cases of neuroinvasive WNv in patients with unusual MDs and unreported MRI findings. CASE REPORT In the first case, a 34-year-old man presented with a 1-week history of disinhibition, agitation, opsoclonus-myoclonus and ataxia syndrome (OMAS), tremor, and facial agnosia. Evaluation of his cerebrospinal fluid (CSF) revealed elevated immunoglobulin (Ig)M against WNv, a high level of protein (98 mg/dL), and an elevated white blood cell (WBC) count (134, 37% lymphocytes). An MRI of the brain showed an area of diffusion restriction in the splenium of the corpus callosum. The patient’s MRI findings and OMA improved significantly after 2 treatments with i.v. IG (IVIG). In the second case, a 57-year-old woman presented with fever, headaches, psychosis, and ataxia; she was subsequently intubated for airway protection. Analysis of her CSF showed elevated IgM against WNv, a high level of protein (79 mg/dL), and elevated WBC count (106, 90% lymphocytes). One week after the onset of symptoms, the patient experienced facial dyskinesia. Later, she developed proximal bilateral lower extremity weakness. An MRI of her lumbar spine showed evidence of myeloradiculitis with contrast enhancement of the conus medullaris and ventral nerve roots. After a single treatment with IVIG, she had partial improvement in weakness. CONCLUSIONS MDs and changes on MRI have been reported in patients with neuroinvasive WNv disease. Our patient with OMAS also had transient splenial diffusion restriction on imaging, which, to the best of our knowledge, has not been previously reported with WNv infection. In both patients, treatment with IVIG resulted in improvement in symptoms.
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