Effect of knocking out mouse on colonic uptake of the microbiota-generated thiamine pyrophosphate and colon physiology.

Humans and mammals obtain vitamin B1 from dietary and gut microbiota sources. A considerable amount of the microbiota-generated vitamin exists in the form of thiamine pyrophosphate (TPP), and colonocytes are capable of absorbing TPP via a specific carrier-mediated process that involves the colonic TPP transporter (cTPPT encoded by ). Little is known about the relative contribution of the SLC44A4 transporter toward total colonic carrier-mediated TPP uptake and its role in colon physiology.

Changes in the innate immune response to SARS-CoV-2 with advancing age in humans.

Background: Advancing age is a major risk factor for respiratory viral infections. The infections are often prolonged and difficult to resolve resulting hospitalizations and mortality. The recent COVID-19 pandemic has highlighted this as elderly subjects have emerged as vulnerable populations that display increased susceptibility and severity to SARS-CoV-2.

Endogenous Retrovirus RNA Expression Differences between Race, Stage and HPV Status Offer Improved Prognostication among Women with Cervical Cancer.

Endogenous human retroviruses (ERVs) are remnants of exogenous retroviruses that have integrated into the human genome. Using publicly available RNA-seq data from 63 cervical cancer patients, we investigated the expression of ERVs in cervical cancers. Four aspects of cervical cancer were investigated: patient ancestral background, tumor HPV type, tumor stage and patient survival.

Spatial Profiling of the Prostate Cancer Tumor Microenvironment Reveals Multiple Differences in Gene Expression and Correlation with Recurrence Risk.

The tumor microenvironment plays a crucial role in both the development and progression of prostate cancer. Furthermore, identifying protein and gene expression differences between different regions is valuable for treatment development. We applied Digital Spatial Profiling multiplex analysis to formalin-fixed paraffin embedded prostatectomy tissue blocks to investigate protein and transcriptome differences between tumor, tumor-adjacent stroma (TAS), CD45+ tumor, and CD45+ TAS tissue.

Expression of Endogenous Retroviral RNA in Prostate Tumors has Prognostic Value and Shows Differences among Americans of African Versus European/Middle Eastern Ancestry.

Endogenous retroviruses (ERVs) are abundant, repetitive elements dispersed across the human genome and are implicated in various diseases. We investigated two potential roles for ERVs in prostate cancer (PCa). First, the PCa of Black Americans (BA) is diagnosed at an earlier median age and at a more advanced stage than the PCa of White Americans (WA).

Vitamin C Enhances Antiviral Functions of Lung Epithelial Cells.

Vitamin C is well documented to have antiviral functions; however, there is limited information about its effect on airway epithelial cells-the first cells to encounter infections. Here, we examined the effect of vitamin C on human bronchial epithelium transformed with Ad12-SV40 2B (BEAS-2B) cells, and observed that sodium-dependent vitamin C transporter 2 (SVCT2) was the primary vitamin C transporter. Transcriptomic analysis revealed that treating BEAS-2B cells with vitamin C led to a significant upregulation of several metabolic pathways and interferon-stimulated genes (ISGs) along with a downregulation of pathways involved in lung injury and inflammation.

RNA expression differences in prostate tumors and tumor-adjacent stroma between Black and White Americans.

Prostate cancer (PCa) in Black Americans (BA) is diagnosed at an earlier median age and a more advanced stage than PCa in White Americans (WA). Tumor-adjacent stroma (TAS) plays a critical role in tumorigenesis of prostate cancer. We examined RNA expression in both tumor and TAS of BA compared to WA.

Transcriptome Analysis of Ovarian and Uterine Clear Cell Malignancies.

Purpose: Ovarian and uterine clear cell carcinomas (CCCs) are rare but associated with poor prognosis. This study explored RNA transcription patterns characteristic of these tumors.

Experimental Design: RNA sequencing (RNA-seq) of 11 ovarian CCCs and five uterine CCCs was performed and compared to publicly available data from high grade serous ovarian cancers (HGSOCs).

Correction: Airway epithelial cells prime plasmacytoid dendritic cells to respond to pathogens via secretion of growth factors.

The original version of this Article contained an error in the spelling of the author Hannah Nguyen, which was incorrectly given as Hannah Ngyuen. This has now been corrected in both the PDF and HTML versions of the Article.

Airway epithelial cells prime plasmacytoid dendritic cells to respond to pathogens via secretion of growth factors.

Plasmacytoid dendritic cells (PDCs) are critical for defense against respiratory viruses because of their propensity to secrete high levels of type I interferons (IFN). The functions of PDCs in the lung can be influenced by airway epithelial cells. We examined the effect of human primary bronchial epithelial cells (PBECs) on PDC functions by performing RNA-sequencing of PDCs after co-culture with air liquid interface differentiated PBECs.

Transcriptional Profiling of Age-Associated Gene Expression Changes in Human Circulatory CD1c+ Myeloid Dendritic Cell Subset.

Immune dysfunction is a hallmark of aging and is thought to be responsible for the age-associated diseases. Dendritic cells (DCs) of the immune system function as initiators and regulators of the immune responses. Recent studies have highlighted the division of labor between various DC subsets.

Overexpression of periostin in stroma positively associated with aggressive prostate cancer.

Background: Periostin is an important extracellular matrix protein involved in cell development and adhesion. Previously, we identified periostin to be up-regulated in aggressive prostate cancer (CaP) using quantitative glycoproteomics and mass spectrometry. The expression of periostin was further evaluated in primary radical prostatectomy (RP) prostate tumors and adjacent non-tumorous prostate tissues using immunohistochemistry (IHC).

The identification of trans-associations between prostate cancer GWAS SNPs and RNA expression differences in tumor-adjacent stroma.

Here we tested the hypothesis that SNPs associated with prostate cancer risk, might differentially affect RNA expression in prostate cancer stroma. The most significant 35 SNP loci were selected from Genome Wide Association (GWA) studies of ~40,000 patients. We also selected 4030 transcripts previously associated with prostate cancer diagnosis and prognosis.

A class of genes in the HER2 regulon that is poised for transcription in breast cancer cell lines and expressed in human breast tumors.

HER2-positive breast cancer accounts for 25% of all cases and has a poor prognosis. Although progress has been made in understanding signal transduction, little is known of how HER2 achieves gene regulation. We performed whole genome expression analysis on a HER2⁺ and HER2⁻ breast cancer cell lines and compared these results to expression in 812 primary tumors stratified by their HER2 expression level.

Role of the adjacent stroma cells in prostate cancer development and progression: synergy between TGF-β and IGF signaling.

This review postulates the role of transforming growth factor-beta (TGF-β) and insulin-like growth factor (IGF-I/IGF-II) signaling in stromal cells during prostate carcinogenesis and progression. It is known that stromal cells have a reciprocal relationship to the adjacent epithelial cells in the maintenance of structural and functional integrity of the prostate. An interaction between TGF-β and IGF signaling occupies a central part in this stromal-epithelial interaction.

An accurate prostate cancer prognosticator using a seven-gene signature plus Gleason score and taking cell type heterogeneity into account.

One of the major challenges in the development of prostate cancer prognostic biomarkers is the cellular heterogeneity in tissue samples. We developed an objective Cluster-Correlation (CC) analysis to identify gene expression changes in various cell types that are associated with progression. In the Cluster step, samples were clustered (unsupervised) based on the expression values of each gene through a mixture model combined with a multiple linear regression model in which cell-type percent data were used for decomposition.

Expression changes in the stroma of prostate cancer predict subsequent relapse.

Biomarkers are needed to address overtreatment that occurs for the majority of prostate cancer patients that would not die of the disease but receive radical treatment. A possible barrier to biomarker discovery may be the polyclonal/multifocal nature of prostate tumors as well as cell-type heterogeneity between patient samples. Tumor-adjacent stroma (tumor microenvironment) is less affected by genetic alteration and might therefore yield more consistent biomarkers in response to tumor aggressiveness.

Hypermethylation of the DLC1 CpG island does not alter gene expression in canine lymphoma.

Background: This study is a comparative epigenetic evaluation of the methylation status of the DLC1 tumor suppressor gene in naturally-occurring canine lymphoma. Canine non-Hodgkin's lymphoma (NHL) has been proposed to be a relevant preclinical model that occurs spontaneously and may share causative factors with human NHL due to a shared home environment. The canine DLC1 mRNA sequence was derived from normal tissue.

Large-scale CpG methylation analysis identifies novel candidate genes and reveals methylation hotspots in acute lymphoblastic leukemia.

This study examined DNA methylation associated with acute lymphoblastic leukemia (ALL) and showed that selected molecular targets can be pharmacologically modulated to reverse gene silencing. A CpG island (CGI) microarray containing more than 3,400 unique clones that span all human chromosomes was used for large-scale discovery experiments and led to 262 unique CGI loci being statistically identified as methylated in ALL lymphoblasts. The methylation status of 10 clones encompassing 11 genes (DCC, DLC-1, DDX51, KCNK2, LRP1B, NKX6-1, NOPE, PCDHGA12, RPIB9, ABCB1, and SLC2A14) identified as differentially methylated between ALL patients and controls was independently verified.