The role of post-transcriptional regulation in SARS-CoV-2 infection and pathogenicity.

The COVID-19 pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus has had a significant impact on global social and economic stability. To combat this, researchers have turned to omics approaches, particularly epitranscriptomics, to limit infection and develop effective therapeutic strategies. Multi-omics can provide the host response dynamics during multiple disease phases to reveal the molecular and cellular landscapes. Epitranscriptomics focuses on the mechanisms of gene transcription in cells and tissues and the relationship between genetic material and epigenetic regulation. This review highlights the role of post-transcriptional regulation in SARS-CoV-2, which affect various processes such as virus infection, replication, immunogenicity, and pathogenicity. The review also explains the formation mechanism of post-transcriptional modifications and how they can be regulated to combat viral infection and pathogenicity.

Research progress of single-cell sequencing in tuberculosis.

Tuberculosis is a major infectious disease caused by Mycobacterium tuberculosis infection. The pathogenesis and immune mechanism of tuberculosis are not clear, and it is urgent to find new drugs, diagnosis, and treatment targets. A useful tool in the quest to reveal the enigmas related to Mycobacterium tuberculosis infection and disease is the single-cell sequencing technique. By clarifying cell heterogeneity, identifying pathogenic cell groups, and finding key gene targets, the map at the single cell level enables people to better understand the cell diversity of complex organisms and the immune state of hosts during infection. Here, we briefly reviewed the development of single-cell sequencing, and emphasized the different applications and limitations of various technologies. Single-cell sequencing has been widely used in the study of the pathogenesis and immune response of tuberculosis. We review these works summarizing the most influential findings. Combined with the multi-molecular level and multi-dimensional analysis, we aim to deeply understand the blank and potential future development of the research on Mycobacterium tuberculosis infection using single-cell sequencing technology.

Landscape of Exhausted T Cells in Tuberculosis Revealed by Single-Cell Sequencing.

Tuberculosis, a contagious bacterial infection caused by Mycobacterium tuberculosis, is a substantial global health problem, impacting millions of lives annually. Exhausted T-cell signatures are critical for predicting clinical responses to tuberculosis infection. To obtain a panoramic transcriptional profile of T cells, we performed single-cell RNA-sequencing analysis of CD4+ T and CD8+ T cells isolated from peripheral blood mononuclear cells of healthy individuals and patients with tuberculosis. We identified seven subsets in CD8+ T cells and eight subsets in CD4+ T cells and elucidated the transcriptomic landscape changes and characteristics of each subset. We further investigated the cell-to-cell relationship of each subgroup of the two cell types. Different signature genes and pathways of exhausted CD4+ and CD8+ T cells were examined. We identified 12 genes with potential associations of T-cell exhaustion after tuberculosis infection. We also identified five genes as potential exhaustion marker genes. The CD8-EX3 subcluster in CD8+ T-exhausted cells was identified as an exhaustion-specific subcluster. The identified gene module further clarified the key factors influencing CD8+ T cell exhaustion. These data provide new insights into T-cell signatures in tuberculosis-exhausted populations. IMPORTANCE Identifying the changes in immune cells in response to infection can provide a better understanding of the effects of Mycobacterium tuberculosis on the host immune system. We performed single-cell RNA-sequencing analysis of CD4+ T and CD8+ T cells isolated from peripheral blood mononuclear cells of healthy individuals and patients with tuberculosis to reveal the cellular characteristics. Different signature genes and pathways of exhausted CD4+ and CD8+ T cells were examined. These will facilitate a more comprehensive understanding of the onset and underlying mechanism of T-cell exhaustion during active Mtb infection.

Studies on the Neuroprotection of Osthole on Glutamate-Induced Apoptotic Cells and an Alzheimer's Disease Mouse Model via Modulation Oxidative Stress.

In the present study, the neuroprotection of osthole (OST) was confirmed. In L-glutamic acid (L-Glu)-damaged HT22 cells, a 3-h pre-incubation with OST-enhanced cell viability suppressed the apoptosis rate; inhibited the activities of caspase-3, caspase-8, and caspase-9; reduced the over-accumulation of intracellular reactive oxygen species; restored the dissipated mitochondrial membrane potential; and regulated the expression levels of B cell lymphoma-2 (Bcl-2), Bax, cleaved poly (ADP-ribose) polymerase (PARP), NF-E2p45-related factor 2 (Nrf2), and its downstream proteins. In amyloid precursor protein/presenilin 1 (APP/PS1) transgenic mice, an 8-week OST administration improved the pathological behaviors related to memory and cognition, and reduced the expression levels of 4-hydroxynonenal, the deposition of ß-amyloid peptides and neuronal fiber tangles formed by the high phosphor-Tau in the brain. OST enhanced the expression levels of Nrf2 and its downstream proteins including superoxide dismutase-1 (SOD-1) and heme oxygenase-1 (HO-1). The present data confirmed the protection of OST against AD-like symptoms via modulating oxidative stress, especially Nrf2 signaling.