LINC00265 Promotes Metastasis and Progression of Hepatocellular Carcinoma by Interacting with E2F1 at The Promoter of CDK2.

Objective: This study aimed to explore biological function of long intergenic non-protein coding RNA 265 (LINC00265) in hepatocellular carcinoma (HCC) cells, and evaluate its potential function as a biomarker. Materials and Methods: In this experimental study, GEPIA database and Kaplan-Meier Plotter database were employed to analyze LINC00265 expression in HCC tissue samples and its predicting value for prognosis. LINC00265 expression in HCC tissues and cells was detected by quantitative real-time polymerase chain reaction (qRT-PCR). After overexpressing and knocking-down of LINC00265 in HCC cells, cell counting kit-8 (CCK-8) and 5-Ethynyl-2'- deoxyuridine (EdU) assays were adopted to detect proliferation of HCC cells. Transwell assay was used to detect migration and invasion of HCC cells. Interaction of LINC00265 with E2F transcription factor 1 (E2F1) was verified by the catRAPID online analysis tool, RNA pull-down experiment and RNA binding protein immunoprecipitation (RIP) assay. Binding of E2F1 to the promoter region of cyclin-dependent kinases 2 (CDK2) was detected by dual-luciferase reporter assay and chromatin immunoprecipitation. Regulatory effects of LINC00265 and E2F1 on CDK2 expression were probed by Western blot. Results: LINC00265 expression was increased in HCC tissues and cells. LINC00265 overexpression promoted proliferation, migration and invasion of HCC cells, and knocking-down LINC00265 worked oppositely. LINC00265 could bind to E2F1 and it could enhance combination of E2F1 and CDK2 promoter regions, thus promoting CDK2 transcription. LINC00265 overexpression promoted expression of CDK2 in HCC cells. Conclusion: Our data suggested that LINC00265 can promote malignant behaviors of HCC cells by recruiting E2F1 to the promoter region of CDK2.

Hidden Telltale Signs in Hyperacute Ischemic Stroke Caused by Aortic Dissection: A Case Report and Post Hoc Analysis.

INTRODUCTION: Rapid identification of hidden telltale signs in hyperacute ischemic stroke caused by aortic dissection (AD) is challenging, mainly owing to the narrow time window for bridging therapy. CASE REPORT: A 63-year-old man was referred for sudden right-side weakness accompanied by a decreased level of consciousness for almost 1 hour and 37 minutes. He had a history of hypertension. His skin was clammy, and on physical examination, there was involuntary chest thumping in the left upper limb. Hyperacute cerebral infarction was considered after no bleeding was observed on emergency head computed tomography, and intravenous thrombolysis with alteplase was administered immediately after. The patient was then taken to the catheter room, ready for endovascular thrombectomy. Stanford type A AD was found by cerebral angiography before endovascular thrombectomy. The infusion of alteplase was stopped immediately during cerebral angiography, but the patient's blood pressure, heart rate, and blood oxygen were still declining progressively, and the degree of consciousness disturbance deepened. The patient died after the combined but failed rescue attempts of multiple departments. CONCLUSION: Hyperacute ischemic stroke caused by AD often hides some telltale signs. Clinicians should master basic clinical skills to exclude AD by looking for these telltale signs hidden in hyperacute ischemic stroke to avoid the fatal consequences of intravenous thrombolysis and/or cerebral angiography within the narrow window of time.

Pseudo P pulmonale pattern associated with severe hypokalemia.

This study presents the case of a 54-year-old man who presented with weakness in his lower extremities and tall P waves on electrocardiography (ECG). At admission, ECG revealed tall P waves (0.32 mV, lead II) at a serum potassium level of 1.21 mmol/L. After potassium supplementation, the amplitude of P waves decreased and returned to normal. A tall P wave may not be a real P pulmonale pattern but a pseudo P pulmonale pattern associated with hypokalemia.

Listeria-based hepatocellular carcinoma vaccine facilitates anti-PD-1 therapy by regulating macrophage polarization.

Recently, patients with advanced cancers have been benefited greatly from immune checkpoint blockade immunotherapy. However, immune checkpoint blockade is still suboptimal in HCC treatment and more immune modifications are needed to achieve an efficient therapeutic goal. Here, we investigated the combined administration of a Listeria-based HCC vaccine, Lmdd-MPFG, and the anti-PD-1 immune checkpoint blockade antibody. We found that Lmdd-MPFG promoted the expression of PD-L1 in HCC cells but resensitized the tumor local T cell to respond to the anti-PD-1 immunotherapy. Mechanistically, the Lmdd-MPFG vaccine activates the NF-κB pathway in the tumor-associated macrophages (TAMs) through the TLR2 and MyD88 pathway, and recruits p62 to activate the autophagy pathway. The overall effect is skewing the TAMs from M2-polarized TAMs into the M1-polarized TAMs. Most importantly, it skewed the cytokine profiles into antitumor one in the tumor microenvironment (TME). This change restores the T-cell reactivity to the anti-PD-1 blockade. Our results suggested that Lmdd-MPFG combined with PD-1 blockade exerted synergistic antitumor effects through modifying TAMs in the TME and removing T-cell inhibitory signals, thereby providing a new potential strategy for HCC treatment.

Long noncoding-RNA component of mitochondrial RNA processing endoribonuclease is involved in the progression of cholangiocarcinoma by regulating microRNA-217.

Cholangiocarcinoma (CCA) is a malignant tumor originating from bile duct epithelium and its incidence is increasing year by year. In recent years, long noncoding RNAs (lncRNAs) have been found to play an important role in the occurrence and progression of malignant tumors. In the present study, for the first time, abnormal expression of lnc-RNA component of mitochondrial RNA processing endoribonuclease (RMRP) and its possible role in CCA were found. We explored the effects of RMRP on various behaviors of CCA cells in vitro and in vivo. In addition, by second-generation sequencing, we explored the microRNA expression profiles that RMRP may affect in the HCCC-9810 cell line. We also validated and explored the role of microRNA-217 (miR-217) with high differential expression by in vitro experiments. Our findings indicated that RMRP can play a part in promoting cancer by regulating the expression of miR-217. RMRP is involved in the progression of CCA and can be a novel indicator of poor prognosis in patients with CCA.

Circulating Long Noncoding RNAs as Biomarkers for Predicting Head and Neck Squamous Cell Carcinoma.

BACKGROUND/AIMS: The anatomical complexity of the head and neck region and the lack of sufficiently specific and sensitive biomarkers often lead to the diagnosis of head and neck squamous cell carcinoma (HNSCC) at advanced stages. To identify novel biomarkers for early diagnosis of primary HNSCC through a minimally invasive method, we investigated circulating long noncoding RNA (lncRNA) levels in plasma of HNSCC patients. METHODS: The global lncRNA expression profiles of HNSCC patients were measured using microarray and next-generation RNA-sequencing (RNA-seq) data from both circulating and tissue samples. The diagnosis prediction model based on the lncRNA signatures and clinical features was evaluated by multi-stage validation and risk score analysis. RESULTS: The data showed that 432 lncRNA transcripts were differentially expressed by fold changes of > 4 in circulating samples and 333 in tissues samples, respectively. Only 12 lncRNAs consistently emerged in these two kinds of samples. After the risk score analysis including a multistage validation, we identified three lncRNAs, namely, HOXA11-AS, LINC00964 and MALAT1, which were up-regulated in the plasma of HNSCC patients compared with those in healthy controls with merged areas under the curve (AUCs) in training and validation sets of 0.925 and 0.839, respectively. CONCLUSION: HOXA11-AS, LINC00964 and MALAT1 might be potential circulating biomarkers for the early detection of HNSCC in the future.

CD24 regulates sorafenib resistance via activating autophagy in hepatocellular carcinoma.

Hepatocellular carcinoma is one of most common solid cancers worldwide. Sorafenib is indicated as a treatment for advanced hepatocellular carcinoma (HCC). However, the clinical efficacy of sorafenib has been severely compromised by the development of drug resistance, and the precise mechanisms of drug resistance remain largely unknown. Here we found that a cell surface molecule, CD24, is overexpressed in tumor tissues and sorafenib-resistant hepatocellular carcinoma cell lines. Moreover, there is a positive correlation between CD24 expression levels and sorafenib resistance. In sorafenib-resistant HCC cell lines, depletion of CD24 caused a notable increase of sorafenib sensitivity. In addition, we found that CD24-related sorafenib resistance was accompanied by the activation of autophagy and can be blocked by the inhibition of autophagy using either pharmacological inhibitors or essential autophagy gene knockdown. In further research, we found that CD24 overexpression also leads to an increase in PP2A protein production and induces the deactivation of the mTOR/AKT pathway, which enhances the level of autophagy. These results demonstrate that CD24 regulates sorafenib resistance via activating autophagy in HCC. This is the first report to describe the relationships among CD24, autophagy, and sorafenib resistance. In conclusion, the combination of autophagy modulation and CD24 targeted therapy is a promising therapeutic strategy in the treatment of HCC.

Enhanced performance of nano-Bi2WO6-graphene as pseudocapacitor electrodes by charge transfer channel.

The nano-Bi2WO6/reduced graphene oxide composite obtained by a simple hydrothermal reaction demonstrates a larger specific capacitance of 922 F/g at a charge and discharge currents of 3 A/g with longer cycle life. The As comparison, pristine Bi2WO6 nanoparticles have poor specific capacitance of 574 F/g at a charge and discharge currents of 2 A/g with weak cycle life. Though analyzing the Cyclic voltammetry curves, it is found that there are two oxidation reaction occurring in the materials: oxidation of Bi (III) to Bi (IV) and Bi (III) to Bi (V). The oxidation of Bi (III) to Bi (IV) is reversible while Bi (III) to Bi (V) will cause nonreversible destroy on structure. In this nano-Bi2WO6/reduced graphene oxide composite, graphene with well conductivity will enhance the electrically conducting as charge transfer channel, so that electrons will be transfer much faster in oxidation and most Bi (III) is oxidized to be Bi (IV) which ensure larger specific capacitance and long cycle life. This nano-Bi2WO6/reduced graphene oxide composite has application prospect in high-performance pseudo-capacitors.

[Effect of electroacupuncture on epileptic EEG and intracellular Ca2+ content in the hippocampus in epilepsy rats].

OBJECTIVE: To study the underlying mechanism of electroacupuncture (EA) in relieving epilepsy in pentylenetetrazole (PTZ)-induced epilepsy rats. METHODS: Twenty SD rats were randomly divided into normal control, model, EA, Nimodipine groups, with 5 cases in each. Epilepsy model was established by intraperitoneal injection of PTZ (32.0 mg/kg), once daily for 28 days. EA (100 Hz, 0.6 mA) was applied to "Baihui" (GV 20) and "Dazhui" (GV 14), once daily for 7 days. For Nimodipine group, the rats were given with nimodipine (0.25 mg/kg, i.p.), once daily for 7 days. Electroencephalogram (EEG) was recorded and the fluorescence intensity of Ca2+ of the hippocampus tissue sections was detected by laser scanning confocal microscope (LSCM) after incubation in artificial cerebrospinal fluid containing Flou-3/AM (10 micromol/L) and pluronic F-127 (5 microl). RESULTS: Compared with model group, the latencies of epileptic EEG seizure prolonged obviously (P < 0.05), and epileptic EEG seizure frequencies decreased significantly (P < 0.05) in EA and Nimodipine groups. The fluorescence intensity of intracellular Ca2+ in hippocampus tissue in model group was obviously higher than that in control group (P < 0.01). In comparison to model group, Ca2+ levels in EA and Nimodipine groups lowered considerably (P < 0.05, P < 0.01). No significant differences were found between EA and Nimodipine groups in the aforementioned 3 indexes (P > 0.05). CONCLUSION: EA has an obvious anti-epileptic effect, which may be closely related to its effect in downregulating the increased hippocampal Ca2+ level in PTZ-kindled epilepsy rats.