reg-eQTL: Integrating transcription factor effects to unveil regulatory variants.

Regulatory single-nucleotide variants (rSNVs) in noncoding regions of the genome play a crucial role in gene transcription by altering transcription factor (TF) binding, chromatin states, and other epigenetic modifications. Existing expression quantitative trait locus (eQTL) methods identify genomic loci associated with gene-expression changes, but they often fall short in pinpointing causal variants. We introduce reg-eQTL, a computational method that incorporates TF effects and interactions with genetic variants into eQTL analysis.

An investigation of plasma cell-free RNA for the detection of colorectal cancer: From transcriptome marker selection to targeted validation.

Regular screening for colorectal cancer (CRC) is critical for early detection and long-term survival. Despite the current screening options available and advancements in therapies there will be around 53,000 CRC related deaths this year. There is great interest in non-invasive alternatives such as plasma cell-free RNA (cfRNA) for diagnostic, prognostic, and predictive applications.

Epigenetic disease markers in primary sclerosing cholangitis and primary biliary cholangitis-methylomics of cholestatic liver disease.

Background: The epigenome, the set of modifications to DNA and associated molecules that control gene expression, cellular identity, and function, plays a major role in mediating cellular responses to outside factors. Thus, evaluation of the epigenetic state can provide insights into cellular adaptions occurring over the course of disease.

Methods: We performed epigenome-wide association studies of primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC) using the Illumina MethylationEPIC Bead Chip.

The FOXP3 Pro-Inflammatory T Cell: A Potential Therapeutic Target in Crohn's Disease.

Background & Aims: The incidence of Crohn's disease (CD) continues to increase worldwide. The contribution of CD4 cell populations remains to be elucidated. We aimed to provide an in-depth transcriptional assessment of CD4 T cells driving chronic inflammation in CD.

Hypoxia-Inducible Factor 1α Stabilization Restores Epigenetic Control of Nitric Oxide Synthase 1 Expression and Reverses Gastroparesis in Female Diabetic Mice.

Background & Aims: Although depletion of neuronal nitric oxide synthase (NOS1)-expressing neurons contributes to gastroparesis, stimulating nitrergic signaling is not an effective therapy. We investigated whether hypoxia-inducible factor 1α (HIF1A), which is activated by high O consumption in central neurons, is a Nos1 transcription factor in enteric neurons and whether stabilizing HIF1A reverses gastroparesis.

Methods: Mice with streptozotocin-induced diabetes, human and mouse tissues, NOS1 mouse neuroblastoma cells, and isolated nitrergic neurons were studied.

AFM is used to study the biophysics of hypertension-induced tachyarrhythmia.

Patients with long-lasting hypertension often suffer from atrial or ventricular arrhythmias. Evidence suggests that mechanical stimulation can change the refractory period and dispersion of the ventricular myocyte action potential through stretch-activated ion channels (SACs) and influence cellular calcium transients, thus increasing susceptibility to ventricular arrhythmias. However, the specific pathogenesis of hypertension-induced arrhythmias is unknown.

Host immunity and KLF 11 deficiency together promote fibrosis in a mouse model of endometriosis.

Background: Endometriosis is a debilitating disease typically characterized by prolific fibrotic scarring. Earlier we reported downregulation of two transcription factors belonging TGF-βR signaling pathway Sp/Krüppel-like factor 11 (KLF11) and 10 (KLF10) in human endometriosis lesions. Here we investigated the role of these nuclear factors and immunity in the scaring fibrosis associated with endometriosis.

Disturbed microbiota-metabolites-immune interaction network is associated with olfactory dysfunction in patients with chronic rhinosinusitis.

Purpose: Olfactory dysfunction (OD) is a debilitating symptom frequently reported by patients with chronic rhinosinusitis (CRS) and it is associated with a dysregulated sinonasal inflammation. However, little information is available about the effect of the inflammation-related nasal microbiota and related metabolites on the olfactory function in these patients. Therefore, the current study aimed to investigate the nasal microbiota-metabolites-immune interactions and their role in the pathogenesis of OD in CRS patients.

Hypomethylation and Overexpression of Th17-Associated Genes is a Hallmark of Intestinal CD4+ Lymphocytes in Crohn's Disease.

Background: The development of Crohn's disease [CD] involves immune cell signalling pathways regulated by epigenetic modifications. Aberrant DNA methylation has been identified in peripheral blood and bulk intestinal tissue from CD patients. However, the DNA methylome of disease-associated intestinal CD4+ lymphocytes has not been evaluated.

Assessment of factors influencing the olfactory bulb volume in patients with post-viral olfactory dysfunction.

Purpose: To investigate the factors influencing the volume of the olfactory bulb (OB) in patients with post-viral olfactory dysfunction (PVOD).

Methods: We collected 92 olfactory bulb volumes from patients with PVOD who underwent a sinus computed tomographic and magnetic resonance imaging (MRI) scan of the head and collected clinical information including gender, age, disease course, minimal cross-sectional area, nasal airway resistance, and olfactory function. OB volume was measured in MRI and the scans were evaluated according to the Lund-Mackay (LM) scoring system.

Performance comparisons of methylation and structural variants from low-input whole-genome methylation sequencing.

Whole-genome methylation sequencing carries both DNA methylation and structural variant information (single nucleotide variant [SNV]; copy number variant [CNV]); however, limited data is available on the reliability of obtaining this information simultaneously from low-input DNA using various library preparation and sequencing protocols. A HapMap NA12878 sample was sequenced with three protocols (EM-sequencing, QIA-sequencing and Swift-sequencing) and their performance was compared on CpG methylation measurement and SNV and CNV detection. At low DNA input (10-25 ng), EM-sequencing was superior in almost all metrics except CNV detection where all protocols were similar.

G9a Modulates Lipid Metabolism in CD4 T Cells to Regulate Intestinal Inflammation.

Background & Aims: Although T-cell intrinsic expression of G9a has been associated with murine intestinal inflammation, mechanistic insight into the role of this methyltransferase in human T-cell differentiation is ill defined, and manipulation of G9a function for therapeutic use against inflammatory disorders is unexplored.

Methods: Human naive T cells were isolated from peripheral blood and differentiated in vitro in the presence of a G9a inhibitor (UNC0642) before being characterized via the transcriptome (RNA sequencing), chromatin accessibility (assay for transposase-accessible chromatin by sequencing), protein expression (cytometry by time of flight, flow cytometry), metabolism (mitochondrial stress test, ultrahigh performance liquid chromatography-tandem mas spectroscopy) and function (T-cell suppression assay). The in vivo role of G9a was assessed using 3 murine models.

Patterns of Gray and White Matter Volume Alterations in Patients With Post-Traumatic Anosmia: A Voxel-Based Morphometry Study.

Objective: Traumatic brain injury is one of the major causes of human olfactory dysfunction and leads to brain structure alterations, mainly in the cortical olfactory regions. Our study aimed to investigate volume changes in the gray matter (GM) and white matter (WM) in patients with post-traumatic anosmia and then to explore the relationship between GM volume and olfactory function.

Methods: Ethics committee approved prospective studies which included 22 patients with post-traumatic anosmia and 18 age- and gender-matched healthy volunteers.

Atomic force microscopy application to study of the biomechanical properties of the aortic intima in the context of early atherosclerosis.

Atherosclerosis is characterized by the infiltration of macrophages, accumulation of lipids, activation of endothelial cells and synthesis of extracellular matrix by vascular smooth muscle cells. However, there have been few atomic force microscopy (AFM) studies of the aortic intima in situ in the context of atherosclerosis. By employing a customized liquid cell for AFM, we investigated the aortic intima obtained from male C57BL/6 ApoE-deficient mice (ApoE ) aged 14 weeks and male C57BL/6 ApoE-sufficient mice (ApoE ) aged between 18 and 26 weeks that were fed a high-fat and high-cholesterol diet for 4 weeks and performed force spectroscopy mapping of the biomechanical properties of the intima.

DNA methylation profile of liver tissue in end-stage cholestatic liver disease.

In this methylome-wide association study of cholestatic liver diseases (primary sclerosing cholangitis and primary biliary cholangitis), the authors aimed to elucidate changes in methylome and pathway enrichment to identify candidate genes Reduced representation bisulfite sequencing was performed on liver tissue from 58 patients with primary sclerosing cholangitis (n = 13), primary biliary cholangitis (n = 20), alcoholic liver disease (n = 21) and live liver donors (n = 4). Pathway enrichment and network analysis were used to explore key genes/pathways. Both cholestatic liver diseases were characterized by global hypomethylation, with pathway enrichment demonstrating distinct genes and pathways associated with the methylome.

Estrogen receptor beta repurposes EZH2 to suppress oncogenic NFκB/p65 signaling in triple negative breast cancer.

Triple Negative Breast Cancer (TNBC) accounts for 15-20% of all breast cancer cases, yet is responsible for a disproportionately high percentage of breast cancer mortalities. Thus, there is an urgent need to identify novel biomarkers and therapeutic targets based on the molecular events driving TNBC pathobiology. Estrogen receptor beta (ERβ) is known to elicit anti-cancer effects in TNBC, however its mechanisms of action remain elusive.

[Prognostic value of olfactory bulb volume in patients with post-viral olfactory dysfunction].

The purpose of this study was to compare the olfactory function examination results of patients with post-viral olfactory dysfunction（PVOD） in different prognostic groups and analyze prognostic factors, especially the influence of olfactory bulb volume（OBV） on prognosis, so as to provide objective basis for clinical diagnosis and treatment. After approval by the hospital ethics committee, the patients with PVOD admitted to Beijing Anzhen Hospital's outpatient department from January 2019 to December 2019 were followed up for at least 1 year. These patients completed the Sniffin' Sticks test and MRI examination of the olfactory pathway before treatment.

[Predictors of posttreatment olfactory improvement in patients with postviral olfactory dysfunction].

To analyzed the results of olfactory function test in patients with post-viral olfactory dysfunction（PVOD）, and evaluated the prognostic factors, so as to provide a basis for clinical diagnosis and treatment. This study included patients who were diagnosed with PVOD at least one year ago in Beijing Anzhen Hospital and whose telephone interviews of subjective olfactory function were available. The general condition of the patients, the results Sniffin' Sticks olfactory test and the event-related potentials（ERPs） were analyzed in different improvement groups.

Differences in olfactory habituation between orthonasal and retronasal pathways.

The odorant arrives at nasal olfactory epithelium ortho- and retronasally. This experiment aimed to study the potential different olfactory habituation in orthonasal and retronasal pathways. 68 subjects were stimulated by constant airflow with an odor (50% phenethyl alcohol, PEA or 5% n-butyl acetate, BA) presented ortho- or retronasally.

BMI1 maintains the Treg epigenomic landscape to prevent inflammatory bowel disease.

FOXP3+ Tregs are expanded within the inflamed intestine of human Crohn's disease, yet FOXP3-mediated gene repression within these cells is lost. The polycomb repressive complexes play a role in FOXP3 target gene regulation, but deeper mechanistic insight is incomplete. We have now specifically identified the polycomb-repressive complex 1 (PRC1) family member, BMI1 in the regulation of a proinflammatory enhancer network in both human and murine Tregs.