Dexmedetomidine-mediated improvement of perioperative neurocognitive disorders by miR-184-3p-mediated NLRP3.

BACKGROUND: Perioperative neurocognitive disorders (PND) is a neurological complication in the perioperative period, which may lead to severe poor prognosis. Dexmedetomidine (Dex) is a commonly used sedative in the perioperative period. However, the effect of intraoperative anesthetic Dex on PND remains complicated and confusing. METHODS: PND model was established using aged male mice, treated with Dex, and subjected to behavioral tests. The effect of Dex on pyroptosis was assessed by western blot, enzyme-linked immunosorbent assay and immunofluorescence. In addition, the miRNA expression profile of PND mice was identified by small RNA sequencing and performed PCR to detect miRNAs. Finally, the effect of miRNA on mice neuron pyroptosis was verified in vitro. RESULTS: We found postoperative cognitive was declined in PND mice compared with control group, while preoperative injection of Dex improved short-term working memory and anxious exploration behavior, alleviated the cognitive impairment. Intriguingly, Dex ameliorated hippocampal inflammation and neuron pyroptosis in PND mice as evidenced by the reduced GSDMD, NLRP3, IL-1ß and IL-18. The miRNA expression profile of PND mice hippocampus was disordered, including 5 miRNAs up-regulated and 17 miRNAs down-regulated, compared to the sham group. Dysregulated miRNAs were mainly enriched in biological functions related to neuronal development and signaling pathways related to pyroptosis. MiR-184-3p was the key miRNA, overexpression of miR-184-3p blocked the inhibitory effect of Dex on neuron pyroptosis, which was manifested as increased expression of GSDMD and NLRP3, increased inflammatory factors IL-1ß and IL-18. CONCLUSIONS: This study revealed that miR-184-3p may mediate NLRP3 to prevent the alleviating effect of Dex on PND, which provides a new potential way to improve the therapeutic intervention of PND.

One-Year Prospective Follow-up of Women With INOCA and MINOCA at a Canadian Women's Heart Centre.

BACKGROUND: Many women with cardiac chest pain and ischemia or myocardial infarction have no obstructive coronary artery disease (INOCA or MINOCA). Studies suggest that these patients have a decreased quality of life and are at increased risk of cardiovascular events. Our study reports 1-year quality of life, frequency of angina, and outcomes following entry into a multidisciplinary Women's Heart Centre (WHC). METHODS: Patients with INOCA and MINOCA completed questionnaires on baseline demographics and clinical presentation. At 1-year, frequency of chest pain, quality of life, depression and anxiety symptoms, and cardiovascular outcomes were reported and compared with baseline. RESULTS: A total of 154 women with nonobstructive coronary artery disease were included in this study (112 patients with INOCA and 42 with MINOCA). Median age was 59 years, and the most common referral was for chest pain (94% in INOCA and 66% in MINOCA). At baseline, 64% of patients with INOCA and 43% of patients with MINOCA did not have specific diagnoses. Following investigations in the WHC, 71.4% of patients with INOCA established a new or a changed diagnosis (most common was coronary microvascular dysfunction at 68%), whereas 60% of patients with MINOCA established new or changed diagnoses (the most common of which was coronary vasospasm at 60%). At 1-year, participants had significantly decreased chest pain, improved quality of life, and improved mental health. CONCLUSIONS: A multidisciplinary WHC significantly increases the yield of a specific diagnosis in patients with INOCA and MINOCA. Further, attending a WHC could significantly improve the clinical and psychological outcomes of women with INOCA and MINOCA.

MiR-326 regulates the proliferation and apoptosis of endometrial cancer by targeting Bcl-2.

AIM: MiR-326 has been investigated to be correlated with multiple types of malignancies; however, the role of miR-326 in endometrial cancer (EC) remains rarely reported. The aim of our research is to investigate the functions of miR-326 in EC and the potential molecular mechanism. METHODS: RT-qPCR was performed to compare the expression of miR-326 and Bcl-2 in normal endometrial epithelial cell line (End1/e6e7) and EC cells lines (HEC-1A, Ishikawa), respectively. Bioinformatic analysis and luciferase assay verified the relationship between miR-326 and the 3'-UTR of Bcl-2. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay, soft agar colony formation assay and the flow cytometry were performed to investigate the functions of miR-326 and Bcl-2 on proliferation and apoptosis in EC. Western blotting was employed to explore the expression of Bcl-2, Bcl2-associated X (Bax) and caspase-3. RESULTS: The expression of miR-326 decreased in EC cell lines compared to normal endometrial epithelial cell line, while Bcl-2 expression was increased in EC cells. Results of MTT and soft agar colony formation assays showed that miR-326 suppressed proliferation in EC cells. In addition, flow cytometry revealed that miR-326 promoted apoptosis in EC cells. Western blotting showed that silencing miR-326 promoted the expression of Bcl-2. Bioinformatics analysis and luciferase assay verified the 3'-UTR of Bcl-2 was a target of miR-326. Furthermore, MTT assay, soft agar colony formation assay and the flow cytometry proved that miR-326 acts as tumor suppressor via inhibiting the expression of Bcl-2. CONCLUSION: MiR-326 acts as a cancer suppressor to inhibit proliferation and promote apoptosis via targeting Bcl-2 axis in EC.

Downregulation of the long noncoding RNA SNHG1 inhibits tumor cell migration and invasion by sponging miR-195 through targeting Cdc42 in oesophageal cancer.

Despite the poor prognosis of oesophageal cancer (EC), the molecular mechanisms of EC are still unclear. In recent years, role of lncRNA in cancer development attracted much attention. The present study aimed to investigate the effects of the long noncoding RNA SNHG1 on the migration and invasion of EC cells and the possible mechanisms involved. The effects of SNHG1 on cell proliferation, migration, and invasion were determined and its relationship with miR-195/Cdc42 axis was investigated. It was found SNHG1 and Cdc42 were significantly upregulated, and miR-195 was significantly downregulated in both EC tissues and cell lines. In addition, the inhibition of either SNHG1 or Cdc42 resulted in suppression of cell proliferation, migration, and invasion, while inhibition of miR-195 led to opposite results and reversed the effects of si-SNHG1. We also observed that higher SNHG1 predicted poorer prognosis of EC patients. In summary, inhibition of SNHG1 can suppress the cell migration and invasion of EC cells by sponging miR-195 through targeting Cdc42. This study might provide deeper insights into the SNHG1/miR-195/Cdc42 axis in EC.

Whole transcriptome sequencing reveals dexmedetomidine-improves postoperative cognitive dysfunction in rats via modulating lncRNA.

The aim of this study was to explore the underlying mechanism and function of dexmedetomidine (Dex)-regulated long non-coding RNAs (lncRNAs) in improving postoperative cognitive dysfunction (POCD) in rats. The established POCD model, Dex treatment model in rats, Morris water maze testing, and HE staining assays were used to evaluate the efficacy of Dex in POCD treatment in rats. Hippocampus samples of rats from the POCD group and the Dex group were used for lncRNA sequencing. The expression of five differentially expressed lncRNAs (DElncRNAs) was verified by quantitative reverse transcription PCR (qRT-PCR). Competing endogenous RNAs (ceRNA) network was constructed using Cytoscape. The concentration of inflammatory cytokines were measured by ELISA. Microglia proliferation and apoptosis were assessed using CCK-8 assay and flow cytometry, respectively. In the Dex group, the escape latency was shorter, neuron cell injury levels were alleviated, and the expression levels of TNF-α and IL-1ß were significantly down-regulated compared with the POCD group. A total of 60 DE lncRNAs were identified, including 16 up- and 44 down-regulated lncRNAs in the Dex group. KEGG pathway analysis revealed that DElncRNAs were significantly enriched in cytokine-cytokine receptor interactions, the p53 signaling pathway, and the NF-kappa B signaling pathway. The qRT-PCR results and ceRNA network suggested that the lncRNA LOC102546895 may play a key role in POCD. LOC102546895 inhibited proliferation while promoting apoptosis in microglial cells and promoted the mRNA and protein expression of the target gene Npas4. Our findings showed that Dex alleviated POCD in rats and regulated lncRNAs expression profile in the hippocampus tissues of rats with POCD. In conclusion, our study outcome proposes that Dex-regulated lncRNA LOC102546895 may play a role in rats with POCD through targeting Npas4.