The present study aimed to examine the expression and function of the metastasis-associated lung adenocarcinoma transcript 1 (MALAT1)/microRNA (miR)-146a/nuclear factor (NF)-κB axis in lipopolysaccharide (LPS)-induced acute kidney injury (AKI). The mRNA levels of MALAT1 and miR-146a in AKI tissues and cells were detected using reverse transcription-quantitative polymerase chain reaction analysis. The NF-κB pathway proteins and cell viability were assessed using western blot analysis and the MTT method, respectively. The secretion of inflammatory factors was determined using the ELISA method. The present study also examined effects of the abnormal expression of MALAT1 and miR-146a on cytokines and the NF-κB pathway. A potential binding region between MALAT1 and miR-146a was confirmed via RNA immunoprecipitation. The results revealed that the upregulation of MALAT1 reduced the expression of miR‑146a, and there was a negative linear correlation between MALAT1 and miR-146a in a RNA-induced silencing complex‑dependent manner. The expression levels of miR-146a were lower in the kidney injury specimens and NRK-52E cells, compared with those in the controls. MALAT1 knockdown and the overexpression of miR-146a reduced the production of phosphorylated inhibitor of NF-κB and np65 protein. miR‑146a was found to be transcriptionally induced by NF-κB, and miR-146a repressed the pro-inflammatory NF-κB pathway and downstream transcription factors. Taken together, these data indicated that the MALAT1/miR‑146a/NF-κB pathway exerted key functions in LPS-induced AKI, and provided novel insights into the mechanisms of this therapeutic candidate for the treatment of the disease.

Abstract. The aim of the present study was to assess the use of tirofiban injections for rescue therapy following artery reocclusion due to intra-luminal thrombosis during endovascular thrombectomy in patients with acute ischemic stroke (AIS). A total of seven cases of patients treated with adjunctive tirofiban injections following failed endovascular thrombectomy due to instant intra-luminal thrombosis were retrospectively assessed. A Solitaire stent was used as the primary thrombectomy device in all patients. Tirofiban was injected intra-arterially via a temporarily deployed Solitaire stent with continuous intravenous infusion for the subsequent 24 h; half of the conventionally recommended dose was employed. Outcome measures included angiographic reperfusion (mTICI), symptomatic intracranial hemorrhage, mortality and functional independence at 90 days (modified Rankin Scale, 0-2). Six patients had occlusions in the middle cerebral artery and one patient had occlusions in the basilar artery. Of the seven patients, five exhibited successful reperfusion (mTICI 2b-3) and achieved functional independence following 90 days. Reperfusion failed in the remaining two patients, who succumbed within 90 days of therapy. No intracranial or extracranial hemorrhage cases were identified. The results of the present study suggest that tirofiban facilitates reperfusion and ameliorates long-term prognosis in patients with AIS undergoing endovascular thrombectomy, and may be safe for those receiving intravenous tissue plasminogen activator therapy.

Background Hepatocellular carcinoma (HCC) is one of the most common malignant cancers in humans and has a high fatality rate. Despite pharmacological advances such as sorafenib and lenvatinib approval, responses are seen only in a limited fraction of HCCs, and the majority of HCC patients do not benefit from this treatment. In recent years, researchers have verified that the long noncoding RNAs (lncRNAs) impact the efficiency of lenvatinib and the prognosis of patients with HCC. Materials and methods This work obtained gene expression profile from an Arraystar lncRNA microarray. Expression of HOTAIRM1, Beclin-1, and p62 in HCC was characterized in clinical HCC tissues of 24 patients with HCC. Overexpression and knockdown experiments were performed in HCC cells to examine the effects of the HOTAIRM1 on lenvatinib sensitivity. The interactions between HOTAIRM1, miR-34a and Beclin-1 were predicted according to GSEA and CNC network. The effects of HOTAIRM1, autophagy and lenvatinib on tumor inhibit were validated in orthotopic tumor-bearing nude mouse model. Results Lenvatinib-resistant HCC cell lines were established using the concentration gradient method. Data from an Arraystar lncRNA microarray indicated that HOTAIRM1, a specific lncRNA located in an evolutionarily highly conserved HOX gene cluster, was differentially expressed between lenvatinib-resistant HCC cells and their parental cells. Expression of HOTAIRM1 and Beclin-1 in HCC was characterized in clinical HCC tissues of 24 patients who have different sensitivity to lenvatinib. Knocking down of HOTAIRM1 decreased the autophagy level in lenvatinib-resistant HCC cells and increased their sensitivity to lenvatinib, especially when combined with autophagy inhibitors both in vitro and in vivo. Further study indicated that knocking down HOTAIRM1 in lenvatinib-resistant cell lines increased the level of miR-34a and inhibited the expression of Beclin-1 in Huh7-R and HepG2-R cells. Investigation according to GSEA and CNC network, lncRNA and nearby coding gene and lncRNA-miRNA analyses demonstrated that the resistance of HCC to lenvatinib was affected by the HOTAIRM1-miR-34a-Beclin-1 regulatory axis. Conclusion HOTAIRM1 is an independent drug resistance factor which significantly associated with the efficacy of lenvatinib in HCC. HOTAIRM1 may downregulation of miR-34a and upregulation of Beclin-1, leading to activation of autophagy, thereby inducing lenvatinib resistance in HCC.