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Epstein-Barr Virus (EBV) exposure and illness is common in undergraduate university students and may affect academic achievement, social life, and quality of life. We designed a study to measure EBV exposure (EBV-IgG, either Epstein-Barr nuclear antigen 1 (EBNA-1)-IgG or viral capsid antigen (VCA)-IgG) and current viral shedding (EBV-DNA) using self-collected oral swabs among university undergraduate students. Of 184 students enrolled, 129 (70.1%) tested positive for EBV-IgG. see more Salivopositivity was associated with being in a current relationship, but not with enrollment year. Forty (21.7%) of the participants tested positive for EBV-DNA, which was associated with all symptom scores, including history of sore throat, fever, swollen glands, muscle weakness, and fatigue in the previous 6 months. Our findings suggest that noninvasive, self-collected oral flocked swabs are feasible and potentially valuable for measuring EBV IgG antibodies and DNA.
Fulminant hepatitis (FH) is a clinical syndrome characterized by sudden and severe liver dysfunction. Dot1L, a histone methyltransferase, is implicated in various physiologic and pathologic processes, including transcription regulation and leukemia. However, the role of Dot1L in regulating inflammatory responses during FH remains elusive.
Propionibacterium acnes (P.acnes)-primed, lipopolysaccharides (LPS)-induced FH was established in C57BL/6 mice and was treated with the Dot1L inhibitor EPZ-5676. Myeloid derived suppressor cells (MDSCs) were depleted by anti-Gr-1 antibody to evaluate their therapeutic roles in Dot1L treatment of FH. Moreover, peripheral blood of patients suffered with FH and healthy controls was collected to determine the expression profile of Dot1L-SOCS1-iNOS axis in their MDSCs.
Here we identified that EPZ-5676, pharmacological inhibitor of Dot1L, attenuated the liver injury of mice subjected to FH. Dot1L inhibition led to decreased T helper 1 cell response and expansion of regulatory T cells (Tregs) during FH. Interestingly, Dot1L inhibition didn't directly target T cells, but dramatically enhanced the immunosuppressive function of MDSCs. Mechanistically, Dot1L inhibition epigenetically suppressed SOCS1 expression, thus inducing inducible nitric oxide synthase (iNOS) expression in a STAT1-dependent manner. Moreover, in human samples, the levels of Dot1L and SOCS1 expression were upregulated in MDSCs, accompanied by decreased expression of iNOS in patients with FH, compared with healthy controls.
Altogether, our findings established Dot1L as a critical regulator of MDSC immunosuppressive function for the first time, and highlighted the therapeutic potential of Dot1L inhibitor for FH treatment.
Altogether, our findings established Dot1L as a critical regulator of MDSC immunosuppressive function for the first time, and highlighted the therapeutic potential of Dot1L inhibitor for FH treatment.
Defining the genetic heterogeneity of intrahepatic biliary epithelial cells (BECs) is challenging, and tools for identifying BEC subpopulations are limited. Here, we characterize the expression of a Sox9
transgene in the liver and demonstrate that green fluorescent protein (GFP) expression levels are associated with distinct cell types.
Sox9
BAC transgenic mice were assayed by immunofluorescence, flow cytometry, and gene expression profiling to characterize invivo characteristics of GFP populations. Single BECs from distinct GFP populations were isolated by fluorescence-activated cell sorting, and functional analysis was conducted in organoid forming assays. Intrahepatic ductal epithelium was grown as organoids and treated with a Yes-associated protein (Yap) inhibitor or bile acids to determine upstream regulation of Sox9 in BECs. Sox9
mice were subjected to bile duct ligation, and GFP expression was assessed by immunofluorescence.
BECs express low or high levels of GFP, whereas periportal hepatocytes express sublow GFP. Sox9
BECs are differentially distributed by duct size and demonstrate distinct gene expression signatures, with enrichment of Cyr61 and Hes1 in GFP
BECs. Single Sox9
cells form organoids that exhibit heterogeneous survival, growth, and HNF4A activation dependent on culture conditions, suggesting that exogenous signaling impacts BEC heterogeneity. Yap is required to maintain Sox9 expression in biliary organoids, but bile acids are insufficient to induce BEC Yap activity or Sox9 invivo and invitro. Sox9
remains restricted to BECs and periportal hepatocytes after bile duct ligation.
Our data demonstrate that Sox9
levels provide readout of Yap activity and delineate BEC heterogeneity, providing a tool for assaying subpopulation-specific cellular function in the liver.
Our data demonstrate that Sox9EGFP levels provide readout of Yap activity and delineate BEC heterogeneity, providing a tool for assaying subpopulation-specific cellular function in the liver.
The purpose of the current study was to compare levels of anxiety sensitivity (AS) across a treatment-seeking sample of individuals primarily using opioids, stimulants, or cannabis. Consistent with the idea that individuals high in AS may be motivated to use substances with real or perceived anxiolytic properties, it was hypothesized that individuals primarily using opioids or cannabis would evidence higher levels of AS compared to individuals primarily using stimulants.
The sample consisted of 110 veterans (including 29 individuals primarily using opioids, 42 primarily using cannabis, and 39 primarily using stimulants) presenting for psychological services to a Posttraumatic Stress Disorder (PTSD) and Substance Use Disorder (SUD) specialty clinic at a large southeastern Veteran Affairs (VA) hospital.
AS levels varied by group with individuals primarily using stimulants evidencing the highest levels followed by those primarily using opioids and then those primarily using cannabis. Individuals primarily using stimulants had statistically significantly higher levels of AS physical concerns compared to individuals primarily using cannabis but not those primarily using opioids. Further, individuals who primarily use opioids did not differ from those primarily using cannabis.
Taken together, these findings call into question the notion that AS may be negatively related to the use of substances that have anxiogenic properties.
Taken together, these findings call into question the notion that AS may be negatively related to the use of substances that have anxiogenic properties.
Homepage: https://www.selleckchem.com/products/secinh3.html
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