Fecal microbiota transplantation from female donors restores gut permeability and reduces liver injury and inflammation in middle-aged male mice exposed to alcohol.

Background: Alcohol misuse, binge drinking pattern, and gender-specific effects in the middle-aged population has been clearly underestimated. In the present study, we focused on understanding gender-specific effects of alcohol exposure on the gut-liver axis and the role of gut microbiota in modulating gender-specific responses to alcohol consumption. Methods: Fifty-two-week-old female and male C57BL/6 mice were fasted for 12 h, and then administered a single oral dose of ethanol (EtOH) (6 g/kg). Controls were given a single dose of PBS. Animals were sacrificed 8 h later. Alternatively, fecal microbiota transplantation (FMT) was performed in 52-week-old male mice from female donors of the same age. Permeability of the large intestine (colon), gut microbiota, liver injury, and inflammation was thoroughly evaluated in all groups. Results: Middle-aged male mice exposed to EtOH showed a significant increase in gut permeability in the large intestine, evaluated by FITC-dextran assay and ZO-1, OCCLUDIN and MUCIN-2 immuno-staining, compared to PBS-treated animals, whilst female mice of the same age also increased their gut permeability, but displayed a partially maintained intestinal barrier integrity. Moreover, there was a significant up-regulation of TLRs and markers of hepatocellular injury, cell death (AST, TUNEL-positive cells) and lipid accumulation (ORO) in male mice after EtOH exposure. Interestingly, FMT from female donors to male mice reduced gut leakiness, modified gut microbiota composition, ameliorated liver injury and inflammation, TLR activation and the senescence phenotype of middle-aged mice. Conclusion: Our findings highlighted the relevance of gender in middle-aged individuals who are exposed to alcohol in the gut-liver axis. Moreover, our study revealed that gender-specific microbiota transplantation might be a plausible therapy in the management of alcohol-related disorders during aging.

Tumor progression locus 2 (TPL2): A Cot-plicated progression from inflammation to chronic liver disease.

The cytoplasmic protein tumor progression locus 2 (TPL2), also known as cancer Osaka thyroid (Cot), or MAP3K8, is thought to have a significant role in a variety of cancers and illnesses and it is a key component in the activation pathway for the expression of inflammatory mediators. Despite the tight connection between inflammation and TPL2, its function has not been extensively studied in chronic liver disease (CLD), a major cause of morbidity and mortality worldwide. Here, we analyze more in detail the significance of TPL2 in CLD to shed light on the pathological and molecular transduction pattern of TPL2 during the progression of CLD. This might result in important advancements and enable progress in the diagnosis and treatment of CLD.

Is Evolutionary Conservation a Useful Predictor for Cancer Long Noncoding RNAs? Insights from the Cancer LncRNA Census 3.

Evolutionary conservation is a measure of gene functionality that is widely used to prioritise long noncoding RNAs (lncRNA) in cancer research. Intriguingly, while updating our Cancer LncRNA Census (CLC), we observed an inverse relationship between year of discovery and evolutionary conservation. This observation is specific to cancer over other diseases, implying a sampling bias in the selection of lncRNA candidates and casting doubt on the value of evolutionary metrics for the prioritisation of cancer-related lncRNAs.

Cancer LncRNA Census 2 (CLC2): an enhanced resource reveals clinical features of cancer lncRNAs.

Long non-coding RNAs (lncRNAs) play key roles in cancer and are at the vanguard of precision therapeutic development. These efforts depend on large and high-confidence collections of cancer lncRNAs. Here, we present the Cancer LncRNA Census 2 (CLC2). With 492 cancer lncRNAs, CLC2 is 4-fold greater in size than its predecessor, without compromising on strict criteria of confident functional/genetic roles and inclusion in the GENCODE annotation scheme. This increase was enabled by leveraging high-throughput transposon insertional mutagenesis screening data, yielding 92 novel cancer lncRNAs. CLC2 makes a valuable addition to existing collections: it is amongst the largest, contains numerous unique genes (not found in other databases) and carries functional labels (oncogene/tumour suppressor). Analysis of this dataset reveals that cancer lncRNAs are impacted by germline variants, somatic mutations and changes in expression consistent with inferred disease functions. Furthermore, we show how clinical/genomic features can be used to vet prospective gene sets from high-throughput sources. The combination of size and quality makes CLC2 a foundation for precision medicine, demonstrating cancer lncRNAs' evolutionary and clinical significance.