Baicalin alleviates chronic obstructive pulmonary disease through regulation of HSP72-mediated JNK pathway.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by airway obstruction and progressive lung inflammation. As the primary ingredient of a traditional Chinese medical herb, Baicalin has been previously shown to possess anti-inflammatory abilities. Thus, the current study aimed to elucidate the mechanism by which baicalin alleviates COPD. METHODS: Baicalin was adopted to treat cigarette smoke in extract-exposed MLE-12 cells after which cell viability and apoptosis were determined. The production of tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), IL-8 were determined by enzyme-linked immunoassay. A COPD mouse model was constructed via exposure to cigarette smoke and lipopolysaccharide, baicalin treatment. Lung function and inflammatory cell infiltration were determined and the production of Muc5AC, TNF-α, IL-6, IL-8 in the bronchoalveolar lavage fluid (BALF) was assayed by ELISA. The effect of HSP72 and JNK on COPD following treatment with baicalin was assessed both in vivo and in vitro by conducting loss- and gain- function experiments. RESULTS: Baicalin improved lung function evidenced by reduction in inflammatory cell infiltration and Muc5AC, TNF-α, IL-6 and IL-8 levels observed in BALF in mice. Baicalin was further observed to elevate cell viability while inhibited apoptosis and TNF-α, IL-6 and IL-8 levels in MLE-12 cells. Baicalin treatment increased HSP72 expression, while its depletion reversed the effect of baicalin on COPD. HSP72 inhibited the activation of JNK, while JNK activation was found to inhibit the effect of baicalin on COPD. CONCLUSIONS: Baicalin upregulated the expression of HSP72, resulting in the inhibition of JNK signaling activation, which ultimately alleviates COPD.

Circ_0110498 facilitates the cisplatin resistance of non-small cell lung cancer by mediating the miR-1287-5p/RBBP4 axis.

BACKGROUND: Circular RNAs (circRNAs) play vital roles in non-small cell lung cancer (NSCLC) progression. Our research analyzed the role of circ_0110498 on the cisplatin (DDP) resistance of NSCLC. METHODS: Cell glycolysis was analyzed by measuring glucose consumption and lactate production. Protein expression was determined by western blot analysis. The expression of circ_0110498, microRNA (miR)-1287-5p and RBBP4 was detected by RT-qPCR assay. Cell counting kit-8, colony formation and transwell assays, together with flow cytometry were conducted to analyze cell DDP resistance, proliferation, metastasis and apoptosis. RESULTS: Circ_0110498 expression was elevated in DDP-resistant NSCLC tissues and cells. Circ_0110498 silencing not only suppressed the DDP resistance of NSCLC cells by inhibiting cell growth, metastasis and glycolysis, but also enhanced the DDP sensitivity of NSCLC tumors. MiR-1287-5p was sponged by circ_0110498, and its inhibitor also reversed the effect of circ_0110498 silencing on the DDP resistance of NSCLC cells. MiR-1287-5p interacted with RBBP4, and RBBP4 overexpression partly reversed the inhibitory effect of miR-1287-5p on the DDP resistance of NSCLC cells. CONCLUSION: Circ_0110498 facilitated DDP resistance partly through mediating the miR-1287-5p/RBBP4 signaling in NSCLC.

Bioinformatic Analysis Identifies of Potential miRNA-mRNA Regulatory Networks Involved in the Pathogenesis of Lung Cancer.

Objective: The purpose of the present study was to explore the biomarkers related to lung cancer based on the bioinformatics method, which might be new targets for lung cancer treatment. Methods: GSE17681 and GSE18842 were obtained from the Gene Expression Omnibus (GEO) database. The differentially expressed miRNAs (DEMs) and genes (DEGs) in lung cancer samples were screened via the GEO2R online tool. DEMs were submitted to the mirDIP website to predict target genes. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were conducted via uploading DEGs to the DAVID database. The protein-protein interaction network (PPI) of the DEGs was analyzed by STRING's online tool. Then, the PPI network was visualized using Cytoscape 3.8.0. Results: 46 DEMs were identified in GSE17681, and the website predicted that there were 873 target genes of these DEMs. 1029 DEGs were identified in the GSE18842 chip. GO analysis suggested that the co-DEGs participated in the canonical Wnt signaling pathway, regulation of the Wnt signaling pathway, a serine/threonine kinase signaling pathway, the Wnt signaling pathway, and cell-cell signaling by Wnt. KEGG analysis results showed the co-DEGs of GSE17681 and GSE18842 were related to the Hippo signaling pathway and adhesion molecules. In addition, six hub genes that were related to lung cancer were identified as hub genes, including mTOR, NF1, CHD7, ETS1, IL-6, and COL1A1. Conclusions: The present study identified six hub genes that were related to lung cancer, including mTOR, NF1, CHD7, ETS1, IL-6, and COL1A1, which might be a potential target for lung cancer.

Transcatheter Arterial Chemoembolization Combined with Simultaneous Cone-beam Computed Tomography-guided Microwave Ablation in the Treatment of Small Hepatocellular Carcinoma: Clinical Experiences From 50 Procedures.

RATIONALE AND OBJECTIVES: To investigate the technical success, safety and outcomes of transcatheter arterial chemoembolization (TACE) combined with simultaneous cone-beam computed tomography (CBCT)-guided microwave ablation (MWA) in small hepatocellular carcinoma (SHCC). MATERIALS AND METHODS: Retrospective analysis of 66 lesions in 50 patients (38 men, 12 women) who underwent TACE combined with simultaneous CBCT-guided MWA for SHCC. After 1 month of treatment, the tumor responses were assessed using the mRECIST criteria, along with interventional-related complications and changes in hepatic and renal function. Moreover, progression-free survival (PFS) and overall survival (OS) were calculated. RESULTS: All patients achieved technical success. The mean target tumor size was 3.4 ± 0.7 (range, 2.2-4.9) cm. The mean energy, ablation duration per tumor, and the mean safety margin were 51.3 ± 8.4 kJ, 6.7 ± 0.8 minutes and 1.4 ± 0.6 cm, respectively. The 1-, 3-, and 5-year PFS rates were 90.0%, 65.4%, and 35.7%, respectively, with a mean PFS of 43.46 months; and the 1-, 3-, and 5-year OS rates were 98.0%, 89.8%, and 74.3%, respectively, with a mean OS of 54.90 months. Multivariate Cox regression analysis further illustrated that TACE combined with MWA in the treatment of a single tumor with a diameter of less than 3 cm was an independent protective factor for PFS and OS (p < 0.001). The patients had no major complications. Among the exceptions, one patient (2%) had an asymptomatic perihepatic effusion that resolved spontaneously, two patients (4%) developed massive right pleural effusion, requiring thoracic drainage, and another patient (2%) developed a hepatic subcapsular hemorrhage required interventional embolization. CONCLUSION: CBCT-guided TACE combined with simultaneous MWA was a safe and successful treatment of SHCC with a high technical efficacy.

Circ_0006988 promotes the proliferation, metastasis and angiogenesis of non-small cell lung cancer cells by modulating miR-491-5p/MAP3K3 axis.

Circular RNAs (circRNAs) are related to the progression of non-small cell lung cancer (NSCLC). However, the roles and mechanism of circ_0006988 are largely unknown. The levels of circ_0006988, Low-Density Lipoprotein Receptor Class A Domain Containing 3 (LDLRAD3), microRNA-491-5p (miR-491-5p), Mitogen-Activated Protein Kinase Kinase Kinase 3 (MAP3K3) were measured using quantitative real-time polymerase-chain reaction (qRT-PCR) and western blot assay. The characteristic of circ_0006988 was analyzed by RNase R assay and Actinomycin D assay. Functional analyses were processed by Cell Counting Kit-8 (CCK-8) assay, 5-ethynyl-2'-deoxyuridine (EdU) assay, colony formation assay, flow cytometry analysis, transwell assay, wound-healing assay and tube formation assay. The interactions between circ_0006988 and miR-491-5p as well as miR-491-5p and MAP3K3 were analyzed by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. Murine xenograft model assay was processed to verify the function of circ_0006988 in vivo. Immunohistochemistry (IHC) assay was conducted to examine the level of Ki67. Circ_0006988 abundance was increased in NSCLC tissues and cells. Circ_0006988 silencing restrained NSCLC cell proliferation, migration, invasion and angiogenesis, and induced apoptosis. Circ_0006988 sponged miR-491-5p, which directly targeted MAP3K3. MiR-491-5p overexpression repressed NSCLC cell malignant behaviors. MiR-491-5p downregulation or MAP3K3 overexpression reversed the effect of circ_0006988 silencing on NSCLC cell progression. In addition, circ_0006988 knockdown reduced xenograft tumor growth. ssCirc_0006988 contributed to the development of NSCLC by miR-491-5p/MAP3K3 axis.

KLF5-induced BBOX1-AS1 contributes to cell malignant phenotypes in non-small cell lung cancer via sponging miR-27a-5p to up-regulate MELK and activate FAK signaling pathway.

BACKGROUND: Non-small cell lung cancer (NSCLC) is a major histological subtype of lung cancer with high mortality and morbidity. A substantial amount of evidence demonstrates long non-coding RNAs (lncRNA) as critical regulators in tumorigeneis and malignant progression of human cancers. The oncogenic role of BBOX1 anti-sense RNA 1 (BBOX1-AS1) has been reported in several tumors. As yet, the potential functions and mechanisms of BBOX1-AS1 in NSCLC are obscure. METHODS: The gene and protein expression was detected by qRT-PCR and western blot. Cell function was determined by CCK-8, colony forming, would healing and transwell assays. Bioinformatics tools, ChIP assays, dual luciferase reporters system and RNA pull-down experiments were used to examine the interaction between molecules. Subcutaneous tumor models in nude mice were established to investigate in vivo NSCLC cell behavior. RESULTS: BBOX1-AS1 was highly expressed in NSCLC tissues and cells. High BBOX1-AS1 expression was associated with worse clinical parameters and poor prognosis. BBOX1-AS1 up-regulation was induced by transcription factor KLF5. BBOX1-AS1 deficiency resulted in an inhibition of cell proliferation, migration, invasion and EMT in vitro. Also, knockdown of BBOX1-AS1 suppressed NSCLC xenograft tumor growth in mice in vivo. Mechanistically, BBOX1-AS1 acted act as a competetive "sponge" of miR-27a-5p to promote maternal embryonic leucine zipper kinase (MELK) expression and activate FAK signaling. miR-27a-5p was confirmed as a tumor suppressor in NSCLC. Moreover, BBOX1-AS1-induced increase of cell proliferation, migration, invasion and EMT was greatly reversed due to the overexpression of miR-27a-5p. In addition, the suppressive effect of NSCLC progression owing to BBOX1-AS1 depletion was abated by the up-regulation of MELK. Consistently, BBOX1-AS1-mediated carcinogenicity was attenuated in NSCLC after treatment with a specific MELK inhibitor OTSSP167. CONCLUSIONS: KLF5-induced BBOX1-AS1 exerts tumor-promotive roles in NSCLC via sponging miR-27a-5p to activate MELK/FAK signaling, providing the possibility of employing BBOX1-AS1 as a therapeutic target for NSCLC patients.

Soluble fms-like tyrosine kinase-1-enriched exosomes suppress the growth of small cell lung cancer by inhibiting endothelial cell migration.

BACKGROUND: Previous studies have reported that soluble fms-like tyrosine kinase-1 (sFlt-1) possesses anti-tumor effects by inhibiting angiogenesis in many cancers. Exosomes can be engineered as delivery vehicles for transferring functional biomolecules, such as proteins, lipids, and nucleic acids (DNA, mRNA, and miRNA) to target cells to affect inflammation, apoptosis, and angiogenesis. The purpose of this study was to investigate whether exosomes can function as efficient carriers of sFlt-1 in vitro and in vivo, to play a role in SCLC therapy. METHODS: We adopted three different methods: TEM, NTA and western blot analysis to characterize the cell-derived exosomes from NCI-H69 SCLC cell line and normal bronchial epithelial BEAS-2B cell line. we next explored the effects of these exosomes on HUVE cell proliferation and migration in vitro.To verify sFlt-1-loaded exosomes suppress the tumor growth in vivo,we established subcutaneous xenografts in nude mice using the NCI-H69 cell line. RESULTS: We observed that NCI-H69-exo significantly increased human umbilical vein endothelial cells (HUVEC) migration compared to BEAS-2B-exo in vitro and in vivo. sFlt-1 protein expression was statistically higher in BEAS-2B-exo than NCI-H69-exo. sFlt-1 protein or sFlt-1-enriched exosomes can inhibit the migration of HUVECs. Furthermore, sFlt-1-enriched exosomes exhibited higher inhibition efficacy on pro-angiogenesis of NCI-H69-exo in comparison with the same concentration of sFlt-1 protein. Intriguingly, sFlt-1-loaded exosomes showed marked anti-tumor activity by inhibiting the growth of NCI-H69 tumor xenografts. CD31 staining revealed that sFlt-1-loaded exosomes significantly reduced the vascular density of experimental mice. sFlt-1-loaded exosomes markedly induced tumor apoptosis and inhibited tumor cell proliferation in mice. CONCLUSION: Exosomes from a SCLC cell line contain low levels of sFlt-1 and significantly increased the migration of HUVECs. SFlt-1-enriched exosomes can inhibit NCI-H69-exo-induced HUVEC migration. Exosomes enriched in sFlt-1 have the potential to be effective therapeutic agents for SCLC.

Primary pulmonary NK/T-cell lymphoma: A case report and literature review.

Extranodal natural killer (NK)/T-cell lymphoma (ENKTL) is an aggressive disease with poor prognosis. The lung is a relatively rare site of involvement. The current study presents a case of primary pulmonary ENKTL with fever and dyspnea, mimicking pneumonia and initially treated with empirical antibiotics. The patient demonstrated rapid deterioration and died shortly following diagnosis. To the best of our knowledge, large-scale investigations referring to primary pulmonary ENKTL are not available. As a result, the exact incidence and clinical features of primary pulmonary ENKTL are unknown. In the current report, a literature review is presented to discuss the clinical characteristics, diagnosis, treatment, and prognosis factors of this malignant disease.

[Expressions and clinical significances of TSLC1 and 4.1B in non-small cell lung cancer].

BACKGROUND: Tumor suppressor in lung cancer-1 (TSLC1) belongs to immunoglobulin superfamily of cell adhesion molecule and differentially expressed in adenocarcinoma of the lung (4.1B)belongs to NF2/ERM/4.1 protein superfamily. They may suppress carcinogenesis via construction of the adjacent cell adhesion stability. The aim of this study is to detect the expressions of TSLC1 and 4.1B in non-small cell lung cancer and the clinical pathological significances. METHODS: The expressions of TSLC1 and 4.1B were detected by RT-PCR in 52 cases of non-small cell lung cancer and corresponding adjacent cancer lung tissues RESULTS: The expressions of TSLC1 and 4.1B in cancer tissues were significantly lower than that in adjacent cancer lung tissues (0.349 ± 0.008 vs 0.555 ± 0.010; 0.209 ± 0.040 vs 0.721 ± 0.071) (P < 0.01). The expressions of TSLC1 and 4.1B showed a significant correlation with cancer differentiation and TNM staging (P < 0.05), but not with gender, age and pathological type (P > 0.05). The expressions of TSLC1 and 4.1B were positively correlated (r=0.471, P < 0.001). CONCLUSIONS: Down-regulated expressions of TSLC1 and 4.1B in non-small cell lung cancer, both may participate in a cascade of non-small cell lung cancer occurrence and development. TSLC1 and 4.1B are promising targets for non-small cell lung cancer diagnosis and treatment.