Butyrate promotes post-stroke outcomes in aged mice via interleukin-22.

Aging increases the risk of stroke, may exacerbate neuroinflammatory responses, reduce angiogenesis, and promote white matter damage post-stroke, all of which contribute to long-term functional recovery. Butyric acid, an important gut microbial metabolite, showed the highest correlation with the outcomes of ischemic stroke, and butyrate was selected as an effective treatment for aged stroke mice. Here, we tested the neurorestorative effect and potential therapeutic mechanisms of butyrate in aged mice with stroke. Aged male C57BL/6 J mice (17-19 months) were subjected to photothrombotic stroke. We performed butyrate supplementation in the drinking water for 3 weeks before surgery until 14 days after the stroke. At 14 days after ischemic stroke, white matter damage, leukocyte infiltration, and blood-brain barrier permeability were all decreased in the aged stroke mice that received the butyrate treatment, which also improved neurological outcomes by stimulating angiogenesis. Stroke reduces the level of interleukin-22 (IL-22) and butyrate treatment significantly enhanced IL-22 expression in the brain. To further validate the mechanisms of butyrate promoting neurological function after stroke, monoclonal antibodies were used to block IL-22 in aged stroke mice when butyrate treatment was provided. Blocking IL-22 in butyrate-treated aged stroke fails to improve functional outcomes and attenuated butyrate-induced angiogenesis, increased axon/white matter density and blood-brain barrier (BBB) integrity, but has no effect on inflammatory cells infiltration. In conclusion, butyrate improves outcomes in aged mice after stroke by promoting angiogenesis and BBB integrity and reducing leukocyte infiltration. To some extent, IL-22 may contribute to butyrate treatment induced vascular remodeling and increased BBB integrity responses in aged stroke mice.

Long noncoding RNA HAS2-AS1 promotes tumor progression in glioblastoma via functioning as a competing endogenous RNA.

Glioblastoma multiforme (GBM) is a refractory tumor with poor prognosis and requires more effective treatment regimens. It has been confirmed that long noncoding RNAs (lncRNAs) substantially regulate various human disease including GBM. However, the biological roles and its underlying molecular mechanisms still need to be further investigated. In this study, the biological function and potential molecular mechanism of lncHAS2-AS1 in GBM were explored. It was discovered that HAS2-AS1 was elevated in glioma tissues and correlated with the prognosis of patients with glioma. Reduction of HAS2-AS1 suppressed the migration and invasion in vitro and in vivo. The transcription factor STAT1 could raise HAS2-AS1 by binding to its promoter region. Besides, HAS2-AS1 could adjust PRPS1 via sponging miR-608 in a direct manner. On the whole, the results of this study evidence that HAS2-AS1 is an oncogene and a potential therapeutic target for GBM.

Decreased miR-325-5p Contributes to Visceral Hypersensitivity Through Post-transcriptional Upregulation of CCL2 in Rat Dorsal Root Ganglia.

Chronic visceral hypersensitivity is an important type of chronic pain with unknown etiology and pathophysiology. Recent studies have shown that epigenetic regulation plays an important role in the development of chronic pain conditions. However, the role of miRNA-325-5p in chronic visceral pain remains unknown. The present study was designed to determine the roles and mechanism of miRNA-325-5p in a rat model of chronic visceral pain. This model was induced by neonatal colonic inflammation (NCI). In adulthood, NCI led to a significant reduction in the expression of miRNA-325-5p in colon-related dorsal root ganglia (DRGs), starting to decrease at the age of 4 weeks and being maintained to 8 weeks. Intrathecal administration of miRNA-325-5p agomir significantly enhanced the colorectal distention (CRD) threshold in a time-dependent manner. NCI also markedly increased the expression of CCL2 (C-C motif chemokine ligand 2) in colon-related DRGs at the mRNA and protein levels relative to age-matched control rats. The expression of CXCL12, IL33, SFRS7, and LGI1 was not significantly altered in NCI rats. CCL2 was co-expressed in NeuN-positive DRG neurons but not in glutamine synthetase-positive glial cells. Furthermore, CCL2 was mainly expressed in isolectin B4-binding- and calcitonin gene-related peptide-positive DRG neurons but in few NF-200-positive cells. More importantly, CCL2 was expressed in miR-325-5p-positive DRG neurons. Intrathecal injection of miRNA-325-5p agomir remarkably reduced the upregulation of CCL2 in NCI rats. Administration of Bindarit, an inhibitor of CCL2, markedly raised the CRD threshold in NCI rats in a dose- and time-dependent manner. These data suggest that NCI suppresses miRNA-325-5p expression and enhances CCL2 expression, thus contributing to visceral hypersensitivity in adult rats.