Probiotics for preventing or treating COVID-19; a systematic review of research evidence and meta-analyses of efficacy for preventing death, severe disease, or disease progression.

COVID-19 variants threaten health globally. Despite improving vaccines and treatments, there is an urgent need for alternative strategies to prevent or reduce the severity of COVID-19. Potential strategies include probiotics, which are safe, inexpensive, globally available and have been studied previously in relation to respiratory infections.

Reimagining Undergraduate Medical Education in a Post-COVID-19 Landscape.

Online education due to the COVID-19 pandemic caused many medical schools to increasingly employ asynchronous and virtual learning that favored student independence and flexibility. At the same time, the COVID-19 pandemic highlighted existing shortcomings of the healthcare field in providing for marginalized and underserved communities. This perspective piece details the authors' opinions as medical students and medical educators on how to leverage the aspects of pandemic medical education to train physicians who can better address these needs.

Colon Tumors in Enterotoxigenic Bacteroides fragilis (ETBF)-Colonized Mice Do Not Display a Unique Mutational Signature but Instead Possess Host-Dependent Alterations in the APC Gene.

Enterotoxigenic Bacteroides fragilis (ETBF) is consistently found at higher frequency in individuals with sporadic and hereditary colorectal cancer (CRC) and induces tumorigenesis in several mouse models of CRC. However, whether specific mutations induced by ETBF lead to colon tumor formation has not been investigated. To determine if ETBF-induced mutations impact the gene, and other tumor suppressors or proto-oncogenes, we performed whole-exome sequencing and whole-genome sequencing on tumors isolated after ETBF and sham colonization of and VC mice, as well as whole-genome sequencing of organoids cocultured with ETBF.

G-protein coupled receptor 35 (GPR35) regulates the colonic epithelial cell response to enterotoxigenic Bacteroides fragilis.

G protein-coupled receptor (GPR)35 is highly expressed in the gastro-intestinal tract, predominantly in colon epithelial cells (CEC), and has been associated with inflammatory bowel diseases (IBD), suggesting a role in gastrointestinal inflammation. The enterotoxigenic Bacteroides fragilis (ETBF) toxin (BFT) is an important virulence factor causing gut inflammation in humans and animal models. We identified that BFT signals through GPR35.

Glucosylceramide production maintains colon integrity in response to Bacteroides fragilis toxin-induced colon epithelial cell signaling.

Enterotoxigenic Bacteroides fragilis (ETBF) is a commensal bacterium of great importance to human health due to its ability to induce colitis and cause colon tumor formation in mice through the production of B. fragilis toxin (BFT). The formation of tumors is dependent on a pro-inflammatory signaling cascade, which begins with the disruption of epithelial barrier integrity through cleavage of E-cadherin.

Correction: Integrated single-cell and bulk gene expression and ATAC-seq reveals heterogeneity and early changes in pathways associated with resistance to cetuximab in HNSCC-sensitive cell lines.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Integrated single-cell and bulk gene expression and ATAC-seq reveals heterogeneity and early changes in pathways associated with resistance to cetuximab in HNSCC-sensitive cell lines.

Background: Identifying potential resistance mechanisms while tumour cells still respond to therapy is critical to delay acquired resistance.

Methods: We generated the first comprehensive multi-omics, bulk and single-cell data in sensitive head and neck squamous cell carcinoma (HNSCC) cells to identify immediate responses to cetuximab. Two pathways potentially associated with resistance were focus of the study: regulation of receptor tyrosine kinases by TFAP2A transcription factor, and epithelial-to-mesenchymal transition (EMT).

Epigenetic Changes Induced by Toxin.

Enterotoxigenic (ETBF) is a Gram-negative, obligate anaerobe member of the gut microbial community in up to 40% of healthy individuals. This bacterium is found more frequently in people with colorectal cancer (CRC) and causes tumor formation in the distal colon of multiple intestinal neoplasia ( ) mice; tumor formation is dependent on ETBF-secreted toxin (BFT). Because of the extensive data connecting alterations in the epigenome with tumor formation, initial experiments attempting to connect BFT-induced tumor formation with methylation in colon epithelial cells (CECs) have been performed, but the effect of BFT on other epigenetic processes, such as chromatin structure, remains unexplored.

Impact of the gut microbiome on the genome and epigenome of colon epithelial cells: contributions to colorectal cancer development.

In recent years, the number of studies investigating the impact of the gut microbiome in colorectal cancer (CRC) has risen sharply. As a result, we now know that various microbes (and microbial communities) are found more frequently in the stool and mucosa of individuals with CRC than healthy controls, including in the primary tumors themselves, and even in distant metastases. We also know that these microbes induce tumors in various mouse models, but we know little about how they impact colon epithelial cells (CECs) directly, or about how these interactions might lead to modifications at the genetic and epigenetic levels that trigger and propagate tumor growth.

The genetic contributions of SNCA and LRRK2 genes to Lewy Body pathology in Alzheimer's disease.

The molecular genetic basis that leads to Lewy Body (LB) pathology in 15-20% of Alzheimer disease cases (LBV/AD) was largely unknown. Alpha-synuclein (SNCA) and Leucine-rich repeat kinase2 (LRRK2) have been implicated in the pathogenesis of Parkinson's disease (PD), the prototype of LB spectrum disorders. We tested the association of SNCA variants with LB pathology in AD.

The cis-regulatory effect of an Alzheimer's disease-associated poly-T locus on expression of TOMM40 and apolipoprotein E genes.

Background: We investigated the genomic region spanning the Translocase of the Outer Mitochondrial Membrane 40-kD (TOMM40) and Apolipoprotein E (APOE) genes, that has been associated with the risk and age of onset of late-onset Alzheimer's disease (LOAD) to determine whether a highly polymorphic, intronic poly-T within this region (rs10524523; hereafter, 523) affects expression of the APOE and TOMM40 genes. Alleles of this locus are classified as S, short; L, long; and VL, very long based on the number of T residues.

Methods: We evaluated differences in APOE messenger RNA (mRNA) and TOMM40 mRNA levels as a function of the 523 genotype in two brain regions from APOE ε3/ε3 white autopsy-confirmed LOAD cases and normal controls.