Extracellular vesicles derived from lung cancer cells promote the progression of lung cancer by delivering miR-151a-5p.

Extracellular vesicles (EVs) participate in the occurrence and development of lung cancer. MiR-151a-5p has been reported to be highly expressed in the tumor tissues of lung cancer. The aim of this work was to investigate whether EVs can affect lung cancer progression by delivering miR-151a-5p. In this work, we found that miR-151a-5p was highly expressed in serum of lung cancer patients. Up-regulation of miR-151a-5p and down-regulation of Nedd4-binding partner-1 (N4BP1) were observed in lung cancer cell lines. The expression of miR-151a-5p was also increased in H520-derived EVs. H520-derived EVs promoted cell proliferation, inhibited apoptosis of H520 cells by delivering miR-151a-5p. EVs containing miR-151a-5p repressed E-cadherin expression and elevated N-cadherin and Vimentin expression to impede epithelial-mesenchymal transition (EMT) of H520 cells. Additionally, the interaction between miR-151a-5p and N4BP1 was verified by luciferase reporter assay, showing that miR-151a-5p interacted with N4BP1. MiR-151a-5p repressed N4BP1 expression by interacting with N4BP1. EVs containing miR-151a-5p promoted malignant phenotypes of H520 cells by targeting N4BP1. Finally, a tumor-bearing mouse model was constructed by inoculation of H520 cells with miR-151a-5p overexpression or knockdown. Overexpression of miR-151a-5p accelerated tumor growth of lung cancer in vivo, and repressed N4BP1 expression in the tumor tissues. Knockdown of miR-151a-5p caused opposite results. In conclusion, this work demonstrated that lung cancer cell-derived EVs secreted miR-151a-5p to promote cell proliferation, and inhibit apoptosis and EMT of lung cancer cells by targeting N4BP1, thereby accelerating lung cancer progression. Thus, this study suggests that EVs-derived miR-151a-5p may be a potential target for lung cancer treatment.

Overexpression of Activating Transcription Factor-2 (ATF-2) Activates Wnt/Ca2+ Signaling Pathways and Promotes Proliferation and Invasion in Non-Small-Cell Lung Cancer.

Previous studies have suggested an association of the expression of activating transcription factor-2 (ATF-2) with the survival time and the activity of the Wnt/Ca2+ signaling pathway in non-small-cell lung cancer (NSCLC). However, the exact role of ATF-2 in tumorigenesis and its underlying mechanism remains unclear. In this study, we study whether ATF-2 regulates the growth and reproduction of NSCLC cells through the Wnt/Ca2+ pathway. The expression of ATF-2 and pathway-related genes in non-small-cell lung cancer was detected by qRT-PCR and Western blotting. CRISPR/Cas9 technology was used to knock out the ATF-2 gene, and pathway inhibitors and agonists were added to induce cultured cells. The expression of pathway genes and the proliferation and invasion ability of A549 lung cancer cells were analyzed. ATF-2 and pathway-related genes were upregulated in NSCLC. The proliferation and invasion ability of A549 lung cancer cells was decreased after only adding pathway inhibitors. The expression of Wnt/Ca2+ pathway protein was decreased when the ATF-2 gene was knocked out, but the expression of Wnt/Ca2+ pathway protein was reversed after the addition of a pathway agonist. These results suggest that ATF-2 acts as an agonist in the Wnt/Ca2+ signaling pathway, promoting the expression of Wnt5a, Wnt11, CaMK II, and NLK in the Wnt/Ca2+ pathway, thereby regulating the proliferation and invasion of NSCLC cells.

Aggravated Respiratory Failure From COVID-19 Infection: Patient Care Management From Nurses in the Intensive Care Unit.

CONTEXT: About 19% of COVID-19-patients undergo hypoxic breathing problems, approximately 14% require intensive oxygen therapy, and 5% require mechanical ventilation and ICU admission. These patients can deteriorate rapidly, so nurses must closely watch them. OBJECTIVE: The study intended to examine the role of emergency nurses as care providers in intensive care units (ICUs). DESIGN: The research team performed a narrative review by searching the Mendeley, Medline, Google Scholar, ScienceDirect, Springer, and PubMed databases. The search used the keywords COVID-19 infection, epidemiology of respiratory failure pathology in COVID-19 infection, involvement of viral spike protein S of SARSCoV-2, SARS CoV2 transmission, pathophysiology of SARSCoV-2 attack-mediated ARDS, transmission of viral particles of SARSCoV-2 in lungs, mechanism of cytokines in lungs, immunomodulatory response changes in lung physiology, and involvement of nursing officer in nursing patient care management in ICU respiratory failure. SETTING: This study were conducted at The First Affiliated Hospital of Nanchang University, China. RESULTS: Nurses are necessarily not only responsible for adequate oxygen management but also for other critical health services to benefit patients, such as control of oxygen saturation and vital signs, to reduce respiratory failure in the ICU. CONCLUSIONS: The diagnosis of the root cause of respiratory failure and its treatment are complex because a variety of pulmonary and extrapulmonary conditions can cause respiratory failure. Methods of treating acute respiratory failure and other respiratory illness require a multidisciplinary, collaborative approach. Nurses are in the best position to determine patients' risks for respiratory distress, observe them during hospitalizations, and evaluate their treatments.

[Corrigendum] Hypoxia­induced internalization of connexin 26 and connexin 43 in pulmonary epithelial cells is involved in the occurrence of non­small cell lung cancer via the P53/MDM2 signaling pathway.

Following the publication of this article, the authors have realized that the corrsesponding author's name was printed incorrectly in the journal: This was mispelled as "Jin Zhou". The corrected name (Jing Zhou) is printed above. The authors regret any inconvenience this has caused, and thank the Editor for allowing them the opportunity to publish a Corrigendum.[the original article was published in International Journal of Oncology 55: 845­859, 2019; DOI: 10.3892/ijo.2019.4867].

Hypoxia­induced internalization of connexin 26 and connexin 43 in pulmonary epithelial cells is involved in the occurrence of non­small cell lung cancer via the P53/MDM2 signaling pathway.

Reports have highlighted an association between connexins (CXs) or gap junction proteins and non­small cell lung cancer (NSCLC). In the present study, it was aimed to elucidate the regulatory mechanism of CX26 and CX43 under hypoxic conditions in NSCLC. Clinical samples were collected for analysis of CX26 and CX43 expression and clinical cancerization followed by quantification of CX26 and CX43 expression. Following the establishment of an in vitro hypoxia model, P53/murine double minute­2 (MDM2) signaling pathway­, proliferation­ and epithelial­mesenchymal transition (EMT)­related genes were quantified to evaluate the influence of CX26 and CX43 on the biological functions of pulmonary epithelial cells in NSCLC. In addition, the proliferation and tumorigenicity of cancer cells were assessed by EdU staining and xenograft tumors, respectively. Decreased expression of CX26 and CX43 was found in cancer tissues compared with surrounding normal tissue. Hypoxia was shown to activate the P53/MDM2 axis and stimulate the downregulation, ubiquitination and degradation of CX26 and CX43, which were translocated from the membrane to the cytoplasm. Low levels of CX26 and CX43 were demonstrated to further promote EMT and the induction of the proliferation and tumorigenicity of cancer cells. These results were reflected by decreased E­cadherin expression and increased N­cadherin expression, along with increased cell migration, promoted cell proliferation ability and elevated relative protein expression of Oct4 and Nanog, and accelerated tumor growth, accompanied by a higher number of metastatic nodes. Taken together, the key observations of the present study demonstrate that the internalization of CX26 and CX43 promoted proliferation, EMT and migration and thus induced NSCLC via aberrant activation of the P53/MDM2 signaling pathway under hypoxic conditions.

Effect of ALDH2 polymorphism on cancer risk in Asians: A meta-analysis.

Numerous studies have investigated the association between ALDH2 gene rs671G>A polymorphism and various cancer type in Asians. However, the results remain inconclusive.We conducted a comprehensive meta-analysis including 63 articles with 66 studies containing 25,682 cases and 47,455 controls retrieved by searching PubMed and Embase electronic databases up to March 5, 2018.Pooled results indicated that ALDH2 gene rs671 polymorphism was significantly associated with the overall cancer risk in Asians (homozygous model: odds ratio [OR] = 0.85, 95% confidence interval [CI] = 0.72-0.99, P = .042; heterozygous model: OR = 1.32, 95% CI = 1.14-1.52, P  < .001; recessive model: OR = 0.73, 95% CI = 0.60-0.88, P = .001; dominant model: OR = 1.32, 95% CI = 1.16-1.51, P < .001; and allele comparison model: OR = 1.11, 95% CI = 1.03-1.19, P = .004), especially in esophageal cancer and among the Chinese and the Japanese.Our results suggest that ALDH2 rs671 polymorphism is associated with the overall cancer risk in Asians. Well-designed prospective studies with more information about gene-environment interaction, such as drinking, should be conducted to validate our findings.

MicroRNA-497-5p negatively regulates the proliferation and cisplatin resistance of non-small cell lung cancer cells by targeting YAP1 and TEAD1.

BACKGROUND: MicroRNAs (miRNAs) are crucial regulators in the pathological processes and drug resistance of lung cancer. In this study, we investigated the role of miR-497-5p in modulating the function of non-small cell lung cancer (NSCLC). METHODS: MiR-497-5p expression in lung cancer tissues and cells was evaluated by qRT-PCR. Cell proliferation was evaluated by CCK-8 assay and colony-formation assay. Cell cycle and cell apoptosis were detected by flow cytometry. The effect of miR-497-5p on the expression of Yes-associated protein 1 (YAP1) and TEA domain family member 1 (TEAD1) was analyzed by qRT-PCR, Western blot and luciferase activity assay. RESULTS: The expression of miR-497-5p was significantly downregulated in lung cancer tissues and cells compared with paired normal tissues and cells. Overexpression of miR-497-5p induced growth retardation and apoptosis of A549 lung cancer cells. Mechanistically, YAP1 and TEAD1 were targeted and downregulated by miR-497-5p. Finally, we found that miR-497-5p increased cisplatin chemosensitivity in A549 cells. CONCLUSIONS: MiR-497-5p suppresses cell proliferation and resistance to cisplatin in NSCLC by downregulating the expression of YAP1 and TEAD1.

[Protection of camelliasaponin C against injury of myocardial cells by anoxia/reoxygenation and mechanism thereof].

OBJECTIVE: To investigate the protective effects of camelliasaponin C (CS-C) pretreatment on myocardial cell injury induced by anoxia/reoxygenation. METHODS: Myocardial cells were obtained from neonatal SD rats, cultured for 3 to 4 days, added into the wells of a 24-well plate, and were divided randomly into five groups (8 wells for each group): control group, anoxia/reoxygenation (A/R) group, added with anoxia culture fluid for 3 h and then added with imitation reperfusion fluid for 1 h, anoxia preconditioning (AP) group, undergoing anoxia for 10 min before A/R, CS-C pretreated group, added with CS-C 3.75 x 10(-7) mol/L 1 h before A/R, and glibenclamide (Glib) pretreated group, added with CS-C 3.75 x 10(-7) mol/L and Glib 12 microm 1 h before A/R. Trypan blue exclusion was used to detect the viability of the cardiomyocytes, the contents of lactate dehydrogenase (LDH) in the supernatant of culture medium was measured. Electron microscopy was used to observe the ultrastructure of the cardiomyocytes. RESULTS: The contents of LDH of the A/R group was 57.8 U/L +/- 6.4 U/L, significantly higher than that of the control group (12.3 U/L +/- 1.7 U/L, P < 0.01), and the LDH value of the CS-C group was 39.8 U/L +/- 3.9 U/L, significantly lower than that of the A/R group (P < 0.01), not significantly different from that of the AP group (32.4 U/L +/- 5.2 U/L, P > 0.05), but significantly higher than that of the control group. The cardiomyocyte viability of the A/R group was 51.0% +/- 1.9%, significantly lower than that of the control group (92.0% +/- 2.0%, P < 0.01), the cardiomyocyte viability of the CS-C pretreatment group was 76.4% +/- 3.5%, significantly higher than that of the A/R group (P < 0.01), but not significantly different from that of the AP group (78.0% +/- 2.0%, P > 0.05). The cardiomyocyte ultrastructure of the A/R group was significantly changed, and the changes of cardiomyocyte ultrastructure in the CS-C pretreatment group were significantly attenuated compared with the A/R group. The content of LDH of the Glib group was 55.8 U/L +/- 5.0 U/L, significantly higher than that of the CS-C pretreatment group (P < 0.05), and the cardiomyocyte viability of the Glib group was 54.1% +/- 3.7%, significantly lower than that of the CS-C pretreatment group (P < 0.05), and the damage to the cardiomyocyte ultrastructure in the Glib group was more severe than in the CS-C group. CONCLUSION: The cardioprotective effect of CS-C pretreatment is similar to that of anoxia preconditioning and the effective mechanism would be related to the opening of ATP-sensitive K(+) channel. Glib can abolish the cardioprotective effect of CS-C pretreatment.