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Long noncoding RNA uc. 173 enhances intestinal epithelial renewal by increasing function of Paneth cell/stem cell niche via mitochondriaLong ncRNA uc.173 has recently been indicated as a promotor of regeneration of the intestinal mucosa. The epithelium of the intestinal mucosa is a rapidly self-renewing tissue in the body, but the renewal process is often defective due to various diseases. However, the exact underlying mechanism remains unknown. Here, we investigated the role of the PC/ISC niche in uc.173-reguated intestinal mucosal growth and further investigated mitochondrial metabolism in this process
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Proteome Remodeling in a Peptide Immunization Animal Model of Anti-NMDAR EncephalitisAnti-NMDAR encephalitis is the most common subtype of autoimmune encephalitis (AIE) and is characterized by GluN1 antibodies. Disease is associated with substantial morbidity and mortality, highlighting critical unmet therapeutic needs. Most animal models of anti-NMDAR encephalitis depend on intracerebroventricular transfer of patient-derived antibodies or cerebrospinal fluid (CSF), or immunization with structurally intact NMDARs. However, recent studies have demonstrated the induction of anti-NMDAR encephalitis in rodent models through GluN1 peptide immunization, with differing effects. Anti-NMDAR antibodies target the amino terminal domain of the GluN1 subunit, and cause receptor loss and associated neuropsychiatric symptoms such as memory impairment, psychosis, and seizures with high morbidity and mortality. The immunopathogenesis remains unclear and therapeutic management of anti-NMDAR encephalitis have been limited by incomplete knowledge of its pathogenesis.
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Transgender Healthcare Online Curriculum: A Partnership Between An Academic Medical Center And Corrections FacilityThe World Professional Association for Transgender Health Standards of Care (WPATH SOC-8) states that all recommendations be applied equally to individuals living in institutions , including those incarcerated. Studies suggest correctional staff have little training in transgender care. To demonstrate a partnership between an academic medical center and a corrections facility and increase knowledge and comfort in transgender healthcare, academic faculty developed an online curriculum as an educational opportunity for state corrections facility staff and clinicians.
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Regulation of gene expression in striatal input regions by cocaine self-administration●Chronic use of illicit drugs impacts behavior, neuronal structure, electrophysiological properties, and gene expression in mutliple brain regions ● Cocaine self-administration significantly alters mitochondrial size in Nucleus Accumbens (NAc) medium spiny neurons ● Disrupting mitochondrial fission blunts behavioral responding for cocaine in a self-administration paradigm Here we examine gene expression in NAc and brain regions that provide inputs to NAc in mice that recieved an acute dose of cocaine or had undergone cocaine self-administration, focusing on mitochondrial-related gene ontology (GO) terms and predictive transcriptional regulation.
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Novel Next-generation Non-catalytic p38alpha/MK2 Immunomodulators with Endothelial-barrier-stabilizing and Anti-inflammatory ActivityWe have previously identified a small three-ring molecule, UM101, targeted to the ED substrate-docking domain of p38alpha MAPK. UM101 modified p38alpha/MK2 signaling, stabilized endothelial barrier and reduced expression of proinflammatory genes. A next-generation analog with modifications on the first and third ring, Gen-1124, has improved anti-inflammatory and endothelial barrier-stabilizing activity, is lung protective in mouse models of influenza and ARDS, and is currently in a Phase II clinical trial in ARDS. To develop additional therapeutic candidates, we designed and synthesized UM101 analogs with modifications on the middle ring and tested the novel compounds for endothelial barrier- stabilizing and anti-inflammatory activity.
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Radiolabeling of human mesenchymal stem cells for imaging of intraarterial delivery to the brainIntra-arterial delivery of cellular therapies might be highly beneficial due to the first-pass effect, lowering total cell dose; however, imaging might be instrumental in achieving high precision. Magnetic labeling was used for this purpose, but it interferes with diagnostic MRI and has low specificity on follow-up scans. Radiolabeling and PET imaging may address both drawbacks, although radiolabeling conditions were never studied systematically, and efficiencies needed to be higher to adapt methods of low- dose intra-arterial interventions. We hypothesize that radiolabeling of human mesenchymal stem cells (hMSCs) might be beneficial by yielding higher sensitivity over a longer period and will provide quantitative results. Therefore, the goal of the current project is to investigate clinically applicable methods for cell tracking. Moreover, we employ a modern radioisotope 89Zr, which allows for long-term (up to 2 weeks) cell biodistribution in the body. Specifically, the radiolabeling will reveal the retention capacities of transfected cells in the target organ (brain) but can also assess the off- target destination of transplanted cells in live animals.
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Novel Mechanism of Action of GEn-1124, a Next-generation Noncatalytic p38alpha/MK2 signal modifier with Endothelial-barrier-stabilizing, Anti-inflammatory, and Lung-protective ActivitiesWe have previously identified a small molecule, SF-7044, targeted to the ED (Glu160/Asp-161) substrate-docking domain of p38alpha MAPK rather than the catalytic site. SF-7044 (Fig. 1) was converted to its dihydrochloride dihydrate salt, GEn-1124, to improve its solubility and stability. GEn-1124 stabilizes endothelial barrier, reduces expression of proinflammatory genes, preserves expression of anti- inflammatory genes, and improves survival in mouse models of acute lung injury. GEn-1124 has completed Phase I clinical testing and a Phase II clinical trial is in progress. This study defines the novel mechanism of GEn-1124 in contrast with p38 catalytic site inhibitors.
