A "safety cap" for improving hospital sanitation and reducing potential disease transmission.

BACKGROUND: During endotracheal intubation, extubation, tracheotomy, and tracheotomy tube replacement, the splashed airway secretions of patients will increase the risk of transmission of SARS-CoV-2 and many other potential viral and bacterial diseases, such as influenza virus, adenovirus, respiratory syncytial virus, rhinovirus, Middle East respiratory coronavirus syndrome (MERS-CoV), Streptococcus pneumoniae, and Mycobacterium tuberculosis. Therefore, it is necessary to establish a barrier between patients and medical workers to reduce the risk of operators' infection with potentially pathogenic microorganisms. METHODS: We designed a "safety cap" that can be connected to the opening of an endotracheal tube or tracheotomy tube to reduce the diffusion area of respiratory secretions during the process of endotracheal intubation, extubation and tracheotomy tube replace, so as to reduce the infection risk of medical workers. RESULTS: Through a series of hydrodynamic simulation analysis and experiments, we demonstrated that the use of "safety cap" can substantially limit the spatter of airway secretions, so as to improve the hospital sanitation. CONCLUSION: The "safety cap" can effectively limit the dissemination of patients' respiratory secretions, thus reducing the risk of potential diseases transmission and may have certain application prospects.

Long noncoding RNA LINC01419 promotes hepatocellular carcinoma malignancy by mediating miR-485-5p/LSM4 axis.

To investigate the effect of long noncoding RNA (LINC01419)/miR-485-5p/LSM4 on the malignant behavior of hepatocellular carcinoma (HCC) cells. The expressions of LINC01419, miR-485-5p, and LSM4 were determined in HCC at the cellular and clinical levels, and cell biological behavior was evaluated. The relationships between LINC01419, miR-485-5p, and LSM4 were predicted and verified. Additionally, the subcellular localization of LINC01419 in HCC cells was analyzed. Finally, an animal experiment was conducted to confirm the effect of LINC01419 silencing on tumor growth. in HCC tissues and cells, LINC01419 and LSM4 were increasingly expressed, but miR-485-5p was decreasingly expressed. LINC01419 negatively regulated miR-485-5p- and miR-485-5p-targeted LSM4. LINC01419 was localized in the cytoplasm of HCC cells. Downregulation of miR-485-5p or upregulation of LSM4 reversed the inhibition of HCC cell malignant behavior by LINC01419 interference. LINC01419 sponges miR-485-5p to upregulate LSM4 expression, thereby facilitating the biological behavior of HCC cells.

LncRNA SNHG3 Facilitates the Malignant Phenotype of Cholangiocarcinoma Cells via the miR-3173-5p/ERG Axis.

BACKGROUND: Long noncoding RNA (lncRNA) small nucleolar RNA host gene 3 (SNHG3) is an oncogenic lncRNA that has been reported in many cancers, but the role of SNHG3 in cholangiocarcinoma (CCA) remains largely unknown. Bioinformatic analysis revealed a regulatory relationship among SNHG3, miR-3173-5p, and ERG. miR-3173-5p is a tumour suppressive miRNA, while ERG is an oncogene. In the present study, we focused on the regulatory effects and molecular mechanisms of SNHG3 in CCA. METHOD: The expression of SNHG3 and miR-3173-5p was evaluated using qRT-PCR analysis. Knockdown of SNHG3 was achieved by shRNA. Cell viability was assessed by MTT assay. Migration and invasion were determined by Transwell assay. Flow cytometry was used to assess cell apoptosis. Western blots were applied to quantify protein levels. Furthermore, using RNA pulldown and dual luciferase assays, the interactions between SNHG3 and miR-3173-5p and between miR-3173-5p and ERG in CCA cells were validated. RESULTS: SNHG3 was significantly upregulated in CCA cells compared with normal human intrahepatic biliary epithelial cells. Knockdown of SNHG3 inhibited the proliferation and migration of CCA cells. Mechanistically, SNHG3-sponged miR-3173-5p, thus releasing the repression of ERG by miR-3173-5p. Rescue experiments showed that the miR-3173-5p/ERG axis mediated the oncogenic effect of SNHG3. CONCLUSION: Taken together, our data suggest that SNHG3 is a pleiotropic oncogenic lncRNA in CCA. Knockdown of SNHG3 expression suppressed malignant phenotypes in CCA cells via the miR-3173-5p/ERG axis.

[Corrigendum] HK2 is associated with the Warburg effect and proliferation in liver cancer: Targets for effective therapy with glycyrrhizin.

Following the publication of the above article, the authors have realized that the Funding section of the Declarations on p. 7 was written incorrectly: The text here should have appeared as follows: 'This work was supported by the Research Fund Subsidy Project of Hunan Provincial Committee on Health Commission (grant no. 20200179) and Xiang Wei Medical Administration Medical Office Memorandum (2019) No. 118 and the Research Fund of Hunan Provincial Department of Education (grant no. 20C1163)'. The authors regret their oversight in providing this incorrect information in the Funding section of their paper. They thank the Editor of Molecular Medicine Reports for allowing them the opportunity to publish this corrigendum, and apologize to the readership of the Journal and to the inappropriately credited funding bodies in question for any inconvenience caused. [the original article was published in Molecular Medicine Reports 23: 343, 2021; DOI: 10.3892/mmr.2021.11982].

HK2 is associated with the Warburg effect and proliferation in liver cancer: Targets for effective therapy with glycyrrhizin.

Glycyrrhizin (GA) is the most essential active ingredient in licorice root, and has a wide range of biological and pharmacological activities. The present study aimed to conduct a detailed analysis of the effects of GA on liver cancer (LC) cell proliferation and the Warburg effect. Hexokinase­2 (HK2) is a glycolytic enzyme that catalyzes the Warburg effect. To this end, the LC HepG2 cell line was transfected with small interfering RNA­HK2 or pCDNA3.1­HK2, followed by GA treatment. A Cell Counting Kit­8 assay and EdU staining were employed to evaluate the proliferation rate of LC cells. The expression levels of HK2 and the phosphorylation level of AKT were measured by reverse transcription­quantitative PCR and western blotting, respectively. Furthermore, the glucose uptake capacity and lactic acid content were assessed by kits, and the glycolysis level was evaluated by assessing the extracellular acidification rate (ECAR) and the oxygen consumption rate (OCR). A pronounced increase in the OCR, and decreases in the cell proliferation, glucose uptake capacity, lactic acid content, ECAR and HK2 expression were detected in LC cells subjected to GA treatment or HK2­knockdown. Conversely, overexpression of HK2 reversed these trends, indicating that glycyrrhizin may inhibit LC cell proliferation and the Warburg effect through suppression of HK2. In addition, it was revealed that the PI3K/AKT signaling pathway was associated with LC cell proliferation and the Warburg effect; notably, treatment of LC cells with the AKT agonist SC79 induced elevation of the ECAR, cell proliferation, glucose uptake capacity, lactic acid content, phosphorylated­AKT and HK2 expression, and suppressed the OCR. In conclusion, GA may inhibit the Warburg effect and cell proliferation in LC by suppressing HK2 through blockade of the PI3K/AKT signaling pathway.

LncRNA NEAT1 promotes cell proliferation, migration, and invasion via the miR-186-5p/PTP4A1 axis in cholangiocarcinoma.

Cholangiocarcinoma (CCA) is a highly aggressive and malignant tumor. In this study, the effect and molecular mechanism of nuclear enriched abundant transcript 1 (NEAT1) in CCA were elucidated. The expressions of NEAT1, microRNA-186-5p (miR-186-5p), and PTP4A1 were measured by quantitative real-time PCR. The protein levels were measured by Western blotting. Kaplan-Meier analysis was performed to create survival curves. The interactions between NEAT1, miR-186-5p, and PTP4A1 were assessed through the dual luciferase reporter assay. Additionally, the cell proliferation, apoptosis, migration, and invasion were measured by colony formation, flow cytometry, the Transwell assay, and the wound healing assay, respectively. NEAT1 and PTP4A1 were significantly upregulated in CCA tissues and cells, but miR-186-5p was downregulated. NEAT1 expression was negatively correlated with the survival of CCA patients and has remarkable correlation with serum CA199 levels and lymph node metastasis. Besides, NEAT1 could act as a molecular sponge for miR-186-5p to upregulate PTP4A1 expression. More importantly, the knockdown of NEAT1 or overexpression of miR-186-5p inhibited the proliferation, migration and invasion of CCA cells, and the inhibition of miR-186-5p reversed the effects of the knockdown of NEAT1. In addition, NEAT1 could also activate the PI3K/AKT signaling pathway and regulate the epithelial-mesenchymal transition (EMT) through the miR-186-5p/PTP4A1 axis. In conclusion, NEAT1 was involved in cell proliferation, migration and invasion in CCA, and the NEAT1/miR-186-5p/PTP4A1/PI3K/AKT axis indicated novel regulatory mechanisms and therapeutics for the treatment of CCA.

Mixed adenoneuroendocrine carcinoma of the hepatic bile duct: a case report and review of the literature.

BACKGROUND: The World Health Organization's updated classification of digestive system neuroendocrine tumors in 2010 first proposed the classification of mixed adenoneuroendocrine carcinoma (MANEC). The incidence of biliary malignant tumors with neuroendocrine tumors accounts for less than 1% of all neuroendocrine tumors. Moreover, the incidence of hilar bile duct with MANEC is very rare. CASE PRESENTATION: A 65-year-old female patient came to our hospital for repeated abdominal pain for more than 4 months and skin sclera yellow staining for 1 week. Contrast-enhanced computed tomography imaging and magnetic resonance results suggested a hilar tumor for Bismuth-Corlette Type II. The patient underwent radical surgery for hilar cholangiocarcinoma. Finally, the patient was diagnosed with hilar bile duct MANEC, staged 1 (pT1N0M0) based on the eighth edition of the AJCC. Histopathology showed that the tumor was a biliary tumor with both adenocarcinoma and neuroendocrine carcinoma. No evidence of recurrence and metastasis after 20 months of follow-up. CONCLUSIONS: We first reported a MANEC that originated in the hilar bile duct. As far as we known, there were few reports of biliary MANEC, and the overall prognosis was poor. We also found that the higher the Ki-67 index, the worse the prognosis of this type of patient. Radical surgery is the most effective treatment.

Leptin stimulates the epithelial­mesenchymal transition and pro­angiogenic capability of cholangiocarcinoma cells through the miR­122/PKM2 axis.

Leptin is an adipokine minimally known for its activities or underlying mechanisms in cholangiocarcinoma. The present study explored the effects of leptin on the epithelial­mesenchymal transition (EMT) and pro­angiogenic capability of cholangiocarcinoma cells, and investigated the underlying mechanisms. Cholangiocarcinoma cells were treated with leptin, and their migration and invasion rates were investigated using Transwell assays. Furthermore, conditioned medium was collected from cholangiocarcinoma cells following leptin treatment and applied to human umbilical vein endothelial cells to assess tube formation. The expression of EMT and pro­angiogenic factors was examined by reverse transcription­quantitative polymerase chain reaction (RT­qPCR) and western blot analyses. Mechanistically, the function of pyruvate kinase muscle isozyme M2 (PKM2) was assessed in leptin­induced phenotypes using siRNA targeting PKM2 (si­PKM2). Bioinformatics screening and luciferase reporter assays were used to reveal microRNA (miR)­122 as the potential mediator between leptin and PKM2. Finally, the associations between leptin and miR­122 or PKM2 levels in patients with cholangiocarcinoma were assessed by ELISA and RT­qPCR. Leptin significantly increased the EMT and pro­angiogenic capability of cholangiocarcinoma cells, visibly inhibited endogenous miR­122 expression, and upregulated PKM2. Furthermore, si­PKM2 inhibited leptin­induced migration, invasion, EMT­associated marker expression levels and the pro­angiogenic capability in cholangiocarcinoma cells. In addition, miR­122 negatively regulated the expression of PKM2. When applied together with leptin, miR­122 was sufficient to reverse the multiple malignancy­promoting effects of leptin. Consistently, the serum leptin level positively correlated with that of PKM2, but negatively with that of miR­122 in patients with cholangiocarcinoma. Leptin, by downregulating miR­122 and elevating PKM2 expression, acts as a pleiotropic pro­malignancy cytokine for cholangiocarcinoma. Therefore, increasing miR­122 expression and inhibiting PKM2 may be future approaches for cholangiocarcinoma treatment.