Circular RNAs (circRNAs) have been identified play a vital role in various different types of cancer via sponging miRNAs (microRNAs). However, their role in lung adenocarcinoma (LUAD) remains largely unclear. In this study, we systematically characterized the circRNA expression profiles in the LUAD cancer tissues and paired adjacent noncancerous tissues. Three circRNAs were found to be significantly upregulated. Among them, has-circRNA-002178 was further confirmed to be upregulated in the LUAD tissues, and LUAD cancer cells. Subsequently, we also found has-circRNA-002178 could enhance PDL1 expression via sponging miR-34 in cancer cells to induce T-cell exhaustion. More importantly, circRNA-002178 could be detected in exosomes of plasma from LUAD patients and could serve as biomarkers for LUAD early diagnosis. Finally, we found circRNA-002178 could be delivered into CD8 + T cells to induce PD1 expression via exosomes. Taken together, our study revealed that circRNA-002178 could act as a ceRNA to promote PDL1/PD1 expression in lung adenocarcinoma.

The mechanisms of idiopathic pulmonary fibrosis (IPF), a rare, devastating disease with a median survival of 3–5 years, are not fully understood. Gastroesophageal reflux disease (GERD) is a frequent comorbidity encountered in IPF. Hypothetically, GERD-associated microaspiration may lead to persistent inflammation impairing lung infrastructure, thereby possibly accelerating the progression of IPF. IPF may increase intrathoracic pressure, which can aggravate GERD and vice versa. On the basis of the possible beneficial effects of antireflux or antacid therapy on lung function, acute exacerbation, and survival, the recent international IPF guideline recommends antacid therapies for patients with IPF, regardless of symptomatic GERD. However, due to newer conflicting data, several national guidelines do not support this recommendation. Elucidation of these questions by further clinical and bench-to-bedside research may provide us with rational clinical diagnostic and therapeutic approaches concerning GERD in IPF. The present review aims to discuss the latest data on the controversial association of IPF and GERD.

Background/Aims: Lung cancer is one of the leading causes for cancer mortality. The poor therapeutic outcome of non-small cell lung carcinoma (NSCLC) is mainly due to late diagnosis and chemoresistance. In this study, we investigated the role of Musashi1 (MSI1) in NSCLC malignancy and chemoresistance. Methods: Colony formation, MTT, glucose uptake and lactate production assays were employed to study lung cancer cell malignancy and chemoresistance. RT-PCR and Western blotting were performed to detect mRNA and protein expressions of genes. We used immunohistochemistry and Pearson correlation analysis to study the relationship of gene expression. Results: We demonstrated that MSI1 was able to promote the proliferation and glucose metabolism of NSCLC cells, and to mediate the sensitivity to chemotherapy drugs in NSCLC cells. Importantly, we found that MSI1 could regulate the activity of Akt signaling. The regulation of NSCLC proliferation, glucose metabolism and chemoresistance by MSI1 was dependent on the modulation of the activity of the Akt signaling pathway. We also found that MSI1 was a target of miR-181a-5p, a microRNA involved in the regulation of cancer development. The expression levels of MSI1 and miR-181a-5p were negatively correlated in NSCLC. Conclusion: MSI1 promotes non-small cell lung carcinoma malignancy and chemoresistance via activating the Akt signaling pathway, which provides a new strategy for the therapy of NSCLC.

Abnormal apoptotic events play an important role in the pathogenesis of emphysema. The B-cell CLL/lymphoma 2 (Bcl-2) family proteins are essential and critical regulators of apoptosis. We determined whether the anti-apoptotic Bcl-2 play a role in the cigarette smoke extract (CSE)-induced emphysema. Furthermore, given the involvement of epigenetics in chronic obstructive pulmonary disease, we hypothesized that the deregulation of Bcl-2 might be caused by gene methylation. The emphysema in BALB/C mice was established by intraperitoneally injection of CSE. 5-aza-2 0 -deoxycytidine (AZA; a demethylation reagent) and phosphate-buffered saline were also administered intraperitoneally as CSE. TUNEL assay was used to assess apoptotic index of pulmonary cells. The methylation status of CpG dinucleotides within the Bcl-2 promoter was observed in all groups by bisulfite sequencing PCR. Pulmonary expression of Bcl-2, Bax, and cytochrome C were measured after four weeks of treatment. The apoptotic index of pulmonary cells in CSE injection group was much higher than control ((25.88 AE 7.55)% vs. (6.28 AE 2.96)%). Compared to control mice, decreased expression of Bcl-2 and high methylation of Bcl-2 promoter was observed in CSE injected mice (0.88 AE 0.08 vs. 0.49 AE 0.11, (3.82 AE 1.34)% vs. (35.68 AE 5.99)%, P < 0.01).CSE treatment induced lung cell apoptosis and decreased lung function. AZA treatment increased Bcl-2 expression with Bcl-2 promoter demethylation. AZA also alleviated the lung cell apoptosis and function failure caused by CSE treatment. The decreased expression of antiapoptotic Bcl-2 might account for the increased apoptosis in CSE induced-emphysema. Apparently, epigenetic alternation played a role in this deregulation of Bcl-2 expression, and it might support the involvement of epigenetic events in the pathogenesis of emphysema.

Gastroesophageal reflux impairs the mucosal barrier in the distal esophagus, allowing chronic exposure of the squamous epithelium to multitudinous stimulations and inducing chronic inflammation. Esophagitis is a response to inflammation of the esophageal squamous mucosa. Our study clarified that alcohol accumulation could aggravate the progress of esophagitis by inducing pyroptosis; however, Ac-YVAD-CMK, an inhibitor of caspase-1, could effectively suppress the expression of IL-1β and IL-18 both in vivo and in vitro, reducing the inflammatory response, which is promised to be an agent to inhibit the progression of esophagitis. Additionally, caspase-1-derived pyroptosis is involved in esophageal cancer.

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Background: Nosocomial pneumonia is a major health and economic burden globally. Multidrug-resistant (MDR) or extensively drug-resistant (XDR) Gram-negative bacteria are the most common causative pathogens in critically-ill patients. Polymyxin B is a salvage therapy for MDR Gram-negative pathogens; however, the current literature on its effectiveness and nephrotoxicity is limited, including in Chinese patients.Methods: We retrospectively analyzed 107 patients with nosocomial pneumonia caused by MDR or XDR Gram-negative bacteria treated with intravenous polymyxin B (2–3 mg/kg/day). Renal function was evaluated on the day before commencement of polymyxin B therapy and on the third and 7 days of treatment. Univariate and multivariate analyses were conducted to determine risk factors for the effectiveness and nephrotoxicity of polymyxin B. Sixty-seven (62.6%) and sixty-five (60.7%) patients had favorable clinical and microbiological responses, respectively. Acute physiology and chronic health evaluation II (APACHE II) scores, cardio-pulmonary resuscitation (CPR) history, numbers of pathogens per patient and a favorable microbiological response were independently associated with favorable clinical outcomes of polymyxin B treatment in Chinese patients with MDR or XDR nosocomial pneumonia. Initial renal dysfunction was not associated with late nephrotoxicity (on day 7), although early nephrotoxicity (on day 3) was independently associated with late nephrotoxicity (OR = 39.43, 95% CI 7.64–203.62, p = 0.00).Conclusion: Our findings support polymyxin B treatment for MDR and XDR pneumonia, with the severity of disease and polymicrobial infection being risk factors for a poor clinical outcome. Nephrotoxicity following 3 days of polymyxin B treatment was found to be a reliable risk factor for later nephrotoxicity.

Background: This experimental design was based on lncRNA LINC01194 to explore the pathogenesis of NSCLC. Methods: RT-qPCR was used to detect the expression of lncRNA LINC01194 and miR-486-5p in NSCLC tissues and cell lines. CCK-8, colony formation, and transwell assays were used to examine the effects of lncRNA LINC01194 and miR-486-5p on NSCLC cell proliferation and migration invasiveness. For target gene prediction and screening, luciferase reporter assays were used to verify downstream target genes for lncRNA LINC01194 and miR-486-5p. The protein expression of CDK4 was detected using Western blotting. The tumor changes in mice were detected by in vivo experiments in nude mice. Results: LncRNA LINC01194 was highly expressed in NSCLC tissues and NSCLC lines (A549, H1299, H460 cells, H1975), and lncRNA LINC01194 significantly promoted cell proliferation and migration of NSCLC cells. MiR-486-5p was identified as a potential target for LINC01194, and miR-486-5p was expressed at a low level in NSCLC tissues and NSCLC lines (A549, H1299, H460 cells, H1975). CDK4 was identified as a potential target for miR-486-5p. LncRNA LINC01194 was able to inhibit miR-486-5p expression and upregulate the expression level of CDK4. Finally, the results of in vivo animal models confirmed that lncRNA LINC01194 promoted NSCLC progression by modulating the miR-486-5p/CDK4 axis. Conclusion: LncRNA LINC01194 promoted the progression of NSCLC by modulating the miR-486-5p/CDK4 axis.