Naringenin, a flavonoid, has antiinflammatory and immunomodulatory properties. We investigated whether naringenin could attenuate allergen-induced airway inflammation and its possible mechanism in a murine model of asthma. Mice were sensitized and challenged with ovalbumin. Some mice were administered with naringenin before ovalbumin challenge. We evaluated the development of airway inflammation and airway reactivity. Interleukin (IL)4, IL13, chemokine (C-C motif) ligand (CCL)5, and CCL11 in bronchoalveolar lavage fluid and serum total IgE were detected by ELISA. IkappaBalpha degradation and inducible nitric oxide synthase (iNOS) in lungs were measured by Western blot. We also tested NF-kappaB binding activity by electrophoretic mobility shift assay. The mRNA levels of iNOS, CCL5, and CCL11 were detected by real-time PCR. Naringenin attenuated ovalbumin-induced airway inflammation and airway reactivity in experimental mice. The naringenin-treated mice had lower levels of IL4 and IL13 in the bronchoalveolar lavage fluid and lower serum total IgE. Furthermore, naringenin inhibited pulmonary IkappaBalpha degradation and NF-kappaB DNA-binding activity. The levels of CCL5, CCL11, and iNOS were also significantly reduced. The results indicated that naringenin may play protective roles in the asthma process. The inhibition of NF-kappaB and the decreased expression of its target genes may account for this phenomenon.

Many flavonoids were demonstrated to possess the antiallergic effect. Here we detected whether apigenin, a flavonoid, can attenuate allergen-induced airway inflammation and what is the possible mechanism in a murine model of asthma. Apigenin decreased the degree of the inflammatory cell infiltration, airway hyperresponsiveness, and total immunoglobulin E levels compared with the ovalbumin group. In addition, apigenin triggered the switching of the immune response to allergens toward a T-helper type 1 (Th1) profile. Our data clearly demonstrated that apigenin exhibits an anti-inflammatory activity in a murine asthma model, and can switch the immune response to allergens toward the Th1 profile.

Breast cancer (BC) has a complex etiology and pathogenesis, and is the most common malignant tumor type in females, in USA in 2018, yet its relevant molecular mechanisms remain largely unknown. The collagen type V α-1 chain (COL5A1) gene is differentially expressed in renal and ovarian cancer. Using bioinformatics methods, COL5A1 was determined to also be a significant gene in BC, but its association with BC has not been sufficiently reported. COL5A1 microarray and relevant clinical data were collected from the Gene Expression Omnibus, The Cancer Genome Atlas and other databases to summarize COL5A1 expression in BC and its subtypes at the mRNA and protein levels. All associated information was comprehensively analyzed by various software. The clinical significance of the mutation was obtained via the cBioPortal. Furthermore, Gene Ontology functional annotation and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were also performed to investigate the mechanism of COL5A1 in BC. Immunohistochemistry was also conducted to detect and confirm COL5A1 expression. It was determined that COL5A1 was highly expressed in BC tissues, compared with normal tissues at the mRNA level [standard mean difference, 0.84; 95% confidence interval (CI), 0.60-1.07; P=0.108]. The area under the summary receiver operator characteristic curve for COL5A1 was 0.87 (95% CI, 0.84-0.90). COL5A1 expression was altered in 32/817 (4%) sequenced samples. KEGG analysis confirmed the most notable pathways, including focal adhesion, extracellular matrix-receptor interaction and regulation of the actin cytoskeleton. Immunohistochemical detection was used to verify the expression of COL5A1 in 136 selected cases of invasive BC tissues and 55 cases of adjacent normal tissues, while the rate of high expression of COL5A1 in BC was up to 90.4%. These results indicated that COL5A1 is highly expressed at the mRNA and protein levels in BC, and the prognosis of patients with BC with high COL5A1 expression may be reduced; therefore, COL5A1 may be used independently or combined with other detection factors in BC diagnosis.

The present study aimed to examine the effects of 2.5 µm particulate matter (PM2.5) on airway inflammation and to investigate the possible underlying mechanism. Specifically, the focus was on the imbalance of T helper (Th)1/Th2 cells and the dysregulated expression of transcription factors, including trans-acting T cell-specific transcription factor 3 (GATA3), runt-related transcription factor 3 (Runx3) and T-box transcription factor TBX21 (T-bet). In this study, ambient PM2.5 was collected and analyzed, male BALB/c mice were sensitized and treated with PBS, ovalbumin (OVA), PM2.5 or OVA + PM2.5. The effects of PM2.5 alone or PM2.5 + OVA on immunopathological changes, the expression of transcription factors GATA3, Runx3 and T-bet, and the imbalance of Th1/Th2 were investigated. It was found that PM2.5 + OVA co-exposure significantly enhanced inflammatory cell infiltration, increased higher tracheal secretions in lung tissue and upregulated respiratory resistance response to acetylcholine compared with PM2.5 or OVA single exposure and control groups. In addition, higher protein and mRNA expression levels of Th2 inflammatory mediators interleukin (IL)-4, IL-5 and IL-13 in bronchoalveolar lavage fluid were observed in PM2.5 + OVA treated mice, whereas the expression levels of GATA3 and STAT6 were exhibited in mice exposed to OVA + PM2.5 compared with the OVA and PM2.5 groups. By contrast, PM2.5 exposure decreased the protein and mRNA expression levels of Th1 cytokine interferon-γ and transcription factors Runx3 and T-bet, especially among asthmatic mice, different from OVA group, PM2.5 exposure only failed to influence the expression of T-bet. To conclude, PM2.5 exposure evoked the allergic airway inflammation response, especially in the asthmatic mouse model and led to Th1/Th2 imbalance. These effects worked mainly by upregulating GATA3 and downregulating Runx3. These data suggested that Runx3 may play an important role in PM2.5-aggravated asthma in BALB/c mice.

Background: Non-small cell lung cancer (NSCLC) is an intractable malignant lung cancer with high rates of metastasis and mortality. Currently, long noncoding RNA nuclear RNA host gene 7 (SNHG7) is recognized as a biomarker of multiple cancers. However, the role of SNHG7 in NSCLC requires further understanding. Methods: The expression of SNHG7, miR-449a and TGIF2 in NSCLC tumors and cells was examined by quantitative real time polymerase chain reaction (qRT-PCR). Cell viability was measured by MTT assay. Cell migration and invasion was conducted using transwell assay. Protein expression of TGIF2, vimentin, N-cadherin and E-cadherin was detected by western blot. The interaction between miR-449a and SNHG7 or TGIF2 was determined by luciferase reporter system, RIP and RNA pull-down assay, respectively. Xenograft mice models were established by subcutaneously injecting A549 cells transfected with sh-SNHG7 and sh-control. Results: SNHG7 expression was upregulated in NSCLC tumors and cells compared with normal tissues and cells. SNHG7 silencing repressed cell proliferation, migration, invasion and epithelial to mesenchymal transition (EMT) in NSCLC. Consistently, SNHG7 knockdown hindered tumor growth in vivo. The subsequent luciferase reporter system, RIP and RNA pull-down assay validated the interaction between miR-449a and SNHG7 or TGIF2. The rescue experiments displayed that miR-449a inhibitor counteracted SNHG7 silencing induced inhibition on proliferation, migration, invasion and EMT. Similarly, restoration of TGIF2 reversed miR-449a mediated inhibition on cell progression. In addition, the results indicated that SNHG7 could regulate cell progression by targeting miR-449a/TGIF2 axis. Conclusion: SNHG7 contributed to cell proliferation, migration, invasion and EMT in NSCLC by upregulating TGIF2 via sponging miR-449a, representing a novel targeted therapy method for NSCLC.

Objective Interstitial lung disease (ILD) is a common and potentially life‐threatening complication for individuals with systemic sclerosis (SSc). The purpose of this study was to complete a systematic review and meta‐analysis on prevalence and risk factors of SSc‐ILD in East Asia. Methods Medline, EMBASE, and Cochrane Library were searched up to January 22, 2021. The Reporting of Observational Studies in Epidemiology (STROBE) statement was applied to access the methodological quality of the eligible studies. Study characteristics and magnitude of effect sizes were extracted. Then, we calculated the pooled prevalence, weighted mean differences (WMDs), pooled odds ratios (ORs) with corresponding 95% confidence intervals (CIs), and performed subgroup analysis, sensitivity analysis, and publication bias with Egger's test. Results Twenty‐seven of 1584 articles were eligible and a total of 5250 patients with SSc were selected in the meta‐analysis. The pooled prevalence of SSc‐ILD in East Asia was 56% (95% CI 49%‐63%). The SSc‐ILD prevalence was higher in China (72%) than in Japan (46%) and Korea (51%). Longer disease duration (WMD = 1.97, 95% CI 0.55‐3.38), diffuse SSc (OR = 2.84, 95% CI 1.91‐4.21), positive anti‐topoisomerase I antibody (ATA) (OR = 4.92, 95% CI 2.74‐8.84), positive anti‐centromere body antibody (ACA) (OR = 0.14, 95% CI 0.08‐0.25), positive anti‐U3 ribonucleoprotein (RNP) antibody (OR = 0.17, 95% CI 0.04‐0.66), and higher erythrocyte sedimentation rate (ESR) (WMD = 6.62, 95% CI 1.19‐12.05) were associated with SSc‐ILD in East Asia. Conclusion Through this systematic review and meta‐analysis, we found that ILD occurs in up to approximately 56% of patients with SSc in East Asia. Longer disease duration, diffuse SSc, positive ATA, negative ACA, negative anti‐U3 RNP antibody, and higher ESR were risk factors for SSc‐ILD.

The long non-coding RNA colon cancer-associated transcript 1 (CCAT1) has been investigated to involve in the progression of non-small cell lung cancer (NSCLC). Thus, this study aims to explore the detailed molecular mechanisms of CCAT1 in NSCLC. The expression of CCAT1, miR-216a-5p, RAP2B, Bax, Bcl-2, and cleaved caspase 3 was detected by qRT-PCR or Western blot. Cell proliferation, apoptosis, migration, and invasion were analyzed using cell counting kit-8, flow cytometry or Transwell assays, respectively. The interaction between miR-216a-5p and CCAT1 or RAP2B was analyzed by luciferase reporter, RNA immunoprecipitation, and pull-down assays. The expression of CCAT1 was elevated in NSCLC, and CCAT1 deletion could inhibit NSCLC cell proliferation, migration, and invasion but induce apoptosis in vitro as well as imped tumor growth in vivo. MiR-216a-5p was confirmed to be a target of CCAT1, and silencing miR-216a-5p could reverse CCAT1 depletion-mediated inhibitory effects on cell tumorigenesis in NSCLC. Besides that, miR-216a-5p was decreased in NSCLC, and miR-216a-5p restoration inhibited cell tumorigenesis by regulating RAP2B, which was verified to be a target of miR-216a-5p. Additionally, co-expression analysis suggested that CCAT1 indirectly regulated RAP2B level by targeting miR-216a-5p in NSCLC cells. Taken together, CCAT1 deletion could inhibit cell progression in NSCLC through miR-216a-5p/RAP2B axis, indicating a novel pathway underlying NSCLC cell progression and providing new potential targets for NSCLC treatment. Impact statement We investigated that CCAT1 expression was elevated in NSCLC and CCAT1 deletion was identified to inhibit cell carcinogenic phenotypes in NSCLC cells via miR-216a-5p/RAP2B axis, which reveals a novel pathway underlying progression in NSCLC cells and providing potential targets for NSCLC treatment.

Background: Pulmonary lymphangitic carcinomatosis (PLC) is characterized by malignant infiltration into lung lymphatic channels from a primary site and is often observed in advanced malignant tumors. This study aimed to evaluate the diagnostic yield of transbronchial lung cryobiopsy in PLC guided by radial endobronchial ultrasound and virtual bronchoscopic navigation (VBN). Methods: This prospective study enrolled 40 patients with clinical and radiologic features indicating PLC.The radial endobronchial ultrasound probe was initially advanced to the region of interest of the desired lobe near the pleura with guidance by VBN. Transbronchial lung biopsy and transbronchial lung cryobiopsy were both performed in the same ROI of all patients with the obtained samples being sent to the pathology laboratory for diagnostic analysis. Procedural complications were recorded. Results: The average number of transbronchial lung biopsy and transbronchial lung cryobiopsy specimens were 4 (3 to 6) and 2 (1 to 3), respectively (t=10.43, P<0.01), with the corresponding mean diameters per biopsy being 3.7 and 8.7 mm (t=12.37, P<0.01). The diagnostic yields of transbronchial lung biopsy and transbronchial lung cryobiopsy were 70% (28/40) and 92.5% (37/40), respectively. The final positive predictive values of transbronchial lung cryobiopsy and transbronchial lung biopsy for PLC were 94.4% (34/36) and 77.8% (28/36), respectively (χ 2 =23.94, P<0.01). Further, 52.2% (12/23) and 81.5% (22/27) of the patients in the transbronchial lung biopsy and transbronchial lung cryobiopsy groups, respectively, were diagnosed with non-small lung cancer after further molecular analysis (χ 2 =19.56, P<0.01). Only 2 (5%) cases presented postoperative pneumothorax. Moreover, 0 (0%), 3 (7.5%), and 17 (42.5%) patients presented severe, moderate, and mild bleeding, respectively. There were no other adverse events or deaths.Conclusions: Transbronchial lung cryobiopsy with the guidance of radial endobronchial ultrasound and VBN without fluoroscopy has a good diagnostic yield for PLC; moreover, it allows one to obtain adequate and intact tissue samples for further molecular analysis.