Underlying Molecular Mechanism and Construction of a miRNA-Gene Network in Idiopathic Pulmonary Fibrosis by Bioinformatics.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease, but its pathogenesis is still unclear. Bioinformatics methods were used to explore the differentially expressed genes (DEGs) and to elucidate the pathogenesis of IPF at the genetic level. The microarray datasets GSE110147 and GSE53845 were downloaded from the Gene Expression Omnibus (GEO) database and analyzed using GEO2R to obtain the DEGs. The DEGs were further analyzed for Gene Ontology (GO) and Kyoto Encyclopedia of Genomes (KEGG) pathway enrichment using the DAVID database. Then, using the STRING database and Cytoscape, a protein-protein interaction (PPI) network was created and the hub genes were selected. In addition, lung tissue from a mouse model was validated. Lastly, the network between the target microRNAs (miRNAs) and the hub genes was constructed with NetworkAnalyst. A summary of 240 genes were identified as DEGs, and functional analysis highlighted their role in cell adhesion molecules and ECM-receptor interactions in IPF. In addition, eight hub genes were selected. Four of these hub genes (VCAM1, CDH2, SPP1, and POSTN) were screened for animal validation. The IHC and RT-qPCR of lung tissue from a mouse model confirmed the results above. Then, miR-181b-5p, miR-4262, and miR-155-5p were predicted as possible key miRNAs. Eight hub genes may play a key role in the development of IPF. Four of the hub genes were validated in animal experiments. MiR-181b-5p, miR-4262, and miR-155-5p may be involved in the pathophysiological processes of IPF by interacting with hub genes.

Competing risk models versus traditional Cox models for prognostic factors' prediction and care recommendation in patients with advanced laryngeal squamous carcinoma: a population-based study.

PURPOSE: To explore the prognostic factors and the optimal treatment modalities for patients with stage IVA laryngeal squamous cell carcinoma (LSCC), so as to improve the survival rate of patients. METHODS: Patients with stage IVA LSCC between 2004 and 2019 were selected from the Surveillance, Epidemiology, and End Results (SEER) database. We used competing risk models to build nomograms for predicting cancer-specific survival (CSS). The effectiveness of the model was assessed using the calibration curves and the concordance index (C-index). The above results were compared with the nomogram established by Cox regression analysis. The patients were grouped into low-risk and high-risk groups by competing risk nomogram formula. And the Kaplan-Meier (K-M) method and log-rank test were used to make sure that these groups had a survival difference. RESULTS: Overall, 3612 patients were included. Older age, black race, a higher N stage, a higher pathological grade, and a larger tumor size were independent risk factors for CSS; married marital status, total/radical laryngectomy, and radiotherapy were protective factors. The C-index was 0.663, 0.633, and 0.628 in the train set and 0.674, 0.639, and 0.629 in the test set of the competing risk model, and 0.672, 0.640, and 0.634 in the traditional Cox nomogram for 1, 3, and 5 years. In overall survival and CSS, the prognosis of the high-risk group was poorer than that of the low-risk group. CONCLUSION: For patients with stage IVA LSCC, a competing risk nomogram was created to help screen risk population and guide clinical decision-making.

α-Asarone alleviates allergic asthma by stabilizing mast cells through inhibition of ERK/JAK2-STAT3 pathway.

Asthma is a heterogeneous disease related to numerous inflammatory cells, among which mast cells play an important role in the early stages of asthma. Therefore, treatment of asthma targeting mast cells is of great research value. α-Asarone is an important anti-inflammatory component of the traditional Chinese medicine Acorus calamus L, which has a variety of medicinal values. To investigate whether α-asarone can alleviate asthma symptoms and its mechanism. In this study, we investigated the effect of α-asarone on mast cell activation in vivo and in vitro. The release of chemokines or cytokines, AHR (airway hyperresponsiveness), and mast cell activation were examined in a mast cell-dependent asthma model. Western blot was performed to determine the underlying pathway. α-Asarone inhibited the degranulation of LAD2 (laboratory allergic disease 2) cells and decreased IL-8, MCP-1, histamine, and TNF-α in vitro. α-Asarone reduced paw swelling and leakage of Evans blue, as well as serum histamine, CCL2, and TNF-α in vivo. In the asthma model, α-asarone showed an inhibitory effect on AHR, inflammation, mast cells activation, infiltration of inflammatory cells, and the release of IL-5 and IL-13 in lung tissue. α-Asarone decreased the levels of phosphorylated JAK2, phosphorylated ERK, and phosphorylated STAT3 induced by C48/80. Our findings suggest that α-asarone alleviates allergic asthma by inhibiting mast cell activation through the ERK/JAK2-STAT3 pathway.

Resveratrol Ameliorates LPS-induced Acute Lung Injury Mouse Model via Induction of Tristetraprolin.

AIM: In this study, we aimed to investigate whether resveratrol has anti-inflammatory effects on LPS-induced ALI via TTP enhancement. BACKGROUND: Acute lung injury (ALI) is a syndrome of diffuse infammatory lung injury with increased pulmonary edema and the rapid onset of hypoxemic respiratory failure. Resveratrol is a stilbenoid, a form of natural phenol, and a phytoalexin produced by a variety of plants in reaction to injury or when they are attacked by pathogens like bacteria or fungi. Resveratrol exhibits a potent antiinflammatory effect in LPS-induced ALI, while the underlying mechanisms remain elusive. OBJECTIVE: Tristetraprolin (TTP) is a RNA binding protein that is an important endogenous inhibitor of inflammation. The objective of the present study is to investigate whether resveratrol has anti- inflammatory effects on LPS-induced ALI via TTP enhancement. METHODS: Forty male C57BL/6 mice were randomly assigned to four groups and intratracheally instilled with 5 mg/kg lipopolysaccharide (LPS) to induce ALI. RESULTS: LPS-induced lung pathological damage, lung edema, and neutrophil infiltration were reduced by resveratrol pretreatment. Furthermore, resveratrol inhibited the LPS-induced rise in TNF- α, IL-1ß and IL-6 levels in BAL fluids. In the LPS-challenged mouse's lung tissue, resveratrol clearly boosted sirtuin1 (SIRT1) and TTP protein expression, while also increasing TTP expression while reducing proinflammatory cytokines. EX527, on the other hand, reversed resveratrol's effects. CONCLUSION: According to our findings, resveratrol attenuated pulmonary inflammation and lung injury in mice with LPS­induced ALI， at least partly correlated with promoting the activation of SIRT1/TTP signaling pathway, highlighting these pathways as potential targets for intervention in LPS -induced lung injury.

A classification based on tumor-stroma ratio and tumor budding for patients with muscle-invasive bladder cancer.

BACKGROUND: Tumor-stroma ratio (TSR) and tumor budding (TB) play important roles in muscle-invasive bladder cancer (MIBC). We developed a rating system (TSR-TB type) based on the morphological evaluation of TSR and TB for predicting patient outcome and using individualized care. METHODS: TSR and TB were assessed in publicly accessible MIBC tumor slides from the TCGA database. MIBC patients were classified as low stromal or high stromal type based on TSR, and high stromal type was further classified as compartmentalized or mixed stromal type based on TB. RESULTS: TSR-TB type was an independent adverse prognostic factor for OS (P < 0.001). Low stromal type had a greater prognosis (P < 0.001) and were enriched for FGFR3 mutations (P = 0.001). The mixed stromal type was distinguished by increased M2 macrophage penetration (P < 0.001), anti-tumor immune activity, DNA repair pathway mutations, and poor survival. GSEA showed that certain cancer-related pathways, such as mitotic spindle, PI3K-AKT-MTOR signalingwere hyperactivated in high stromal type (all FDR<0.05). Furthermore, mixed stromal type demonstrated enhanced activation of epithelial mesenchymal transformation (EMT), inflammatory response (all FDR<0.05). CONCLUSION: TSR and TB-based MIBC classification coincides with patient survival and molecular alterations. The identified subtypes may have important implications for individualized MIBC therapy.

PTEN participates in airway remodeling of asthma by regulating CD38/Ca2+/CREB signaling.

Both phosphatase and tensin homologue deleted on chromosome ten (PTEN) and cluster of differentiation 38 (CD38) have been suggested to be key regulators of the pathogenesis of asthma. However, the precise role and molecular mechanisms by which PTEN and CD38 are involved in airway remodeling throughout asthma pathogenesis remains poorly understood. This study aimed to elucidate the role of PTEN and CD38 in airway remodeling of asthma. Exposure to tumor necrosis factor-α (TNF-α) in airway smooth muscle (ASM) cells markedly decreased PTEN expression, and increased expression of CD38. Overexpression of PTEN suppressed the expression of CD38 and downregulated proliferation and migration induced by TNF-α stimulation, which was partially reversed by CD38 overexpression. PTEN/CD38 axis regulated Ca2+ levels and cyclic AMP response-element binding protein (CREB) phosphorylation in TNF-α-stimulated ASM cells. The in vitro knockdown of CD38 or overexpression of PTEN remarkably restricted airway remodeling and decreased Ca2+ concentrations and CREB phosphorylation in asthmatic mice. CD38 overexpression abolished the inhibitory effects of PTEN overexpression on airway remodeling. These findings demonstrate that PTEN inhibits airway remodeling of asthma through the downregulation of CD38-mediated Ca2+/CREB signaling, highlighting a key role of PTEN/CD38/Ca2+/CREB signaling in the molecular pathogenesis of asthma.

Notch1 contributes to TNF-α-induced proliferation and migration of airway smooth muscle cells through regulation of the Hes1/PTEN axis.

Notch1 has been implicated in asthma pathogenesis. However, the function of Notch1 in regulating airway smooth muscle (ASM) cell proliferation and migration during airway remodeling of asthma remains unknown. Using an in vitro model induced by tumor necrosis factor (TNF)-α, we reported in this study that Notch1 participated in TNF-α-induced proliferation and migration of ASM cells. Our results demonstrated that Notch1 expression was significantly upregulated in ASM cells exposed to TNF-α. Notch1 inhibition significantly repressed TNF-α-induced ASM cell proliferation and migration, while Notch1 overexpression promoted the opposite effect. Moreover, Notch1 inhibition downregulated the expression of Notch-1 intracellular domain (NICD) and Hes1, while upregulated PTEN expression in TNF-α-exposed cells. Notably, Hes1 overexpression partially reversed the Notch1-inhibition-mediated inhibitory effect on TNF-α-induced ASM cell proliferation and migration. In addition, the promoting effect of Notch1 inhibition on PTEN expression was markedly abrogated by Hes1 overexpression. Overall, these findings demonstrated that Notch1 inhibition repressed TNF-α-induced ASM cell proliferation and migration by modulating the Hes1/PTEN signaling axis, a finding that highlights the involvement of Notch1/Hes1/PTEN in regulating airway remodeling of asthma.

Study of the Anatomical Structure of the Nasopharyngeal Cavity and Distribution of the Air Flow Field.

To build a biomechanical numerical model of the nasopharynx, construct an accurate computerized numerical description of its specific anatomical structures, analyze the distribution of air flow field, starting with the anatomical structure of the pharyngeal recess, correlate its anatomical characteristics with the occurrence and development of nasopharyngeal carcinoma from the perspective of biomechanics. In this study, the nasal and nasopharyngeal cavities of healthy male adult, with the pharyngeal recess in an open state, were scanned by CT to obtain DICOM imaging data. Then, they were imported into Mimics 20.0 to build a model which was recorded in binary STL format. Each file was imported into Geomagic studio 12.0 to construct a 3D model saved in an IGES format. Then, it was imported into ANSYS Workbench for numerical simulation of air flow field. The authors found that:Above all, the causes and pathogenesis of nasopharyngeal carcinoma can be identified from the perspective of biomechanics through the construction of a 3D model and analysis of the characteristics of air flow field. With more in-depth research, it is expected that a more solid scientific foundation will be created for related quantitative analysis.

Isoimperatorin reduces the effective dose of dexamethasone in a murine model of asthma by inhibiting mast cell activation.

Adverse effects that result from dexamethasone (DEX) use are common and serious in patients with asthma. Therefore, alternative anti-inflammatory treatments are being investigated. Isoimperatorin (ISO), an active natural furocoumarin, possesses multiple pharmacological properties, including an anti-inflammation effect. In this study, investigations were conducted on the effect of ISO on mast cell (MC) activation in vitro and whether ISO could reduce the effective dose of DEX in a mast cell-dependent murine model of asthma in vivo. Calcium imaging was used to assess intracellular Ca2+ mobilization. Enzyme-linked immunosorbent assay was used to measure the chemokines release. Western blot analysis was conducted to investigate the underlying pathway. Airway inflammation and hyperresponsiveness (AHR) were examined in an asthma model. ISO inhibited Ca2+ flux and MC degranulation via Lyn/PLCγ1/PKC, ERK, and P38 MAPK pathways. In the asthma model, ISO, in combination with DEX, showed an additive inhibitory effect on AHR, inflammation, and the number of activated MCs in the lungs and decreased the levels of interleukin (IL)-4, IL-5, IL-6, IL-13, tumor necrosis factor (TNF)-a, and C-C motif chemokine ligand (CCL)-2 in bronchoalveolar lavage fluid. A combination of DEX and ISO may be appropriate if a decrease in the steroid dose is desired owing to dose-dependent adverse effects.

Inhibition of Ezrin suppresses cell migration and invasion in human nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is one of the most severe types of malignant cancer of the head and neck as it is difficult to treat. Ezrin is highly expressed in numerous types of cancer. However, the role of Ezrin in NPC has not been fully investigated and further studies are required in order to uncover its therapeutic potential in the treatment of NPC. The aim of the present study was to investigate the expression of Ezrin in human NPC and to evaluate the effect of knockdown of Ezrin using small interfering (si)-RNA on NPC cell migration and invasion. The expression levels of Ezrin were determined using reverse transcription-quantitative polymerase chain reaction, immunohistochemical staining and western blotting. Following transfection of Ezrin-siRNA into NPC cells, cell invasion and migration were analyzed and the mRNA expression levels of matrix metalloproteinase(MMP)-2 and MMP9 were determined. The results revealed that the expression of Ezrin was markedly increased in human NPC tissue samples compared with normal adjacent nasopharyngeal tissue samples. Ezrin was also highly expressed in the NPC cell lines 6-10B and C6661 when compared with the normal nasopharyngeal cell line NP69. Transfection of NPC cell lines with siRNA targeting Ezrin significantly inhibited NPC cell migration and invasion, and downregulated the mRNA expression level of MMP2; however, no effect was observed on MMP9 mRNA expression. At the same time, knockdown of Ezrin significantly decreased the expression levels of phosphatidylinositol 3-kinase (PI3K) and phosphorylated protein kinase B (Akt), which downregulated the mRNA expression of MMP2. In conclusion, the results revealed that knockdown of Ezrin suppressed NPC migration and invasion by reducing the mRNA expression of MMP2 via the PI3K/Akt signaling pathway. These results highlight the important role of Ezrin in NPC cell migration and invasion. In addition, they indicate that silencing of Ezrin may serve as a potential therapeutic strategy to treat human NPC.

SETD7 promotes TNF-α-induced proliferation and migration of airway smooth muscle cells in vitro through enhancing NF-κB/CD38 signaling.

The inflammation-induced the excessive proliferation and migration of airway smooth muscle (ASM) cells in the airway wall contribute to airway remodeling in asthma pathogenesis. SET domain-containing lysine methyltransferase 7 (SETD7) has emerged as one of the key regulators of inflammation. Yet, the function of SETD7 in regulating inflammation-induced ASM cell proliferation and invasion remains unclear. In the present study, we aimed to investigate the function of SETD7 in regulating ASM cell proliferation and invasion induced by tumor necrosis factor (TNF)-α in vitro. Our results showed that SETD7 expression was upregulated in ASM cells stimulated with TNF-α. Silencing SETD7 significantly decreased TNF-α-induced ASM cell proliferation and migration, while SETD7 overexpression exhibited the opposite effect. Notably, silencing SETD7 decreased the activation of nuclear factor (NF)-κB and reduced the expression of CD38 induced by TNF-α. Blocking NF-κB activation significantly abrogated the promotional effect of SETD7 overexpression on CD38 expression. Moreover, overexpression of CD38 partially reversed the inhibitory effect of SETD7 silencing on TNF-α-induced ASM cell proliferation and migration. Overall, these results demonstrate that SETD7 regulates TNF-α-induced ASM cell proliferation and migration through modulation of NF-κB/CD38 signaling, suggesting a potential role of SETD7 in asthma airway remodeling.

Epoxymicheliolide, a novelguaiane-type sesquiterpene lactone, inhibits NF­κB/COX­2 signaling pathways by targeting leucine 281 and leucine 25 in IKKß in renal cell carcinoma.

Parthenolide (PTL) is a sesquiterpene lactone compound obtained from Tanacetum parthenium (feverfew) and inhibits the activation of nuclear factor (NF)-κB. Epoxymicheliolide (EMCL) is a compound which is structurally related to PTL; however, EMCL is more stable under acidic and alkaline conditions. As a biologically active molecule, the detailed mechanism by which EMCL inhibits tumor activity remains to be elucidated. The present study evaluated the effect of EMCL on renal cell carcinoma (RCC) cells and identified the underlying mechanisms. It was found that treatment with EMCL significantly inhibited the proliferation of RCC cells in vitro and increased the induction of apoptosis by activating the mitochondria- and caspase-dependent pathway. Simultaneously, EMCL suppressed cell invasion and metastasis by inhibiting epithelial-mesenchymal transition, as observed in a microfluidic chip assay. Furthermore, using immunofluorescence analysis, an electrophoretic mobility shift assay and a dual-luciferase reporter assay, it was shown that treatment with EMCL significantly suppressed the expression of cyclooxygenase­2 by inhibiting the translocation of NF­κB p50/p65 and the activity of NF­κB. Collectively, the results indicated that EMCL suppressed tumor growth by inhibiting the activation of NF­κB and suggested that EMCL may be a novel anticancer agent in the treatment of RCC.

Melatonin potentiates the antitumor effect of curcumin by inhibiting IKKß/NF-κB/COX-2 signaling pathway.

Curcumin, a natural polyphenolic compound, has commonly been used as a food additive or in many traditional medicine remedies for over 2,000 years in many Asian countries. Melatonin is a hormone secreted from pineal glands of mammals and possesses diverse physiological functions. Both curcumin and melatonin have the effective potential to inhibit proliferation of various types of cancers, but there is no report on their combination for bladder cancer treatment, and the underlying mechanism remains poorly understood. In the present study, we investigated whether the combination of curcumin and melatonin leads to an enhanced inhibition of cell proliferation in bladder cancer cells. Our results showed that the combinational treatment enhanced the repression of nuclear translocation of NF-κB and their binding on COX-2 promoter via inhibiting IKKß activity, resulting in inhibition of COX-2 expression. In addition, combined treatment with curcumin and melatonin induced cell apoptosis in bladder cancer through enhancing the release of cytochrome c from the mitochondrial intermembrane space into the cytosol. These results, therefore, indicated that melatonin synergized the inhibitory effect of curcumin against the growth of bladder cancer by enhancing the anti-proliferation, anti-migration, and pro-apoptotic activities, and provide strong evidence that combined treatment with curcumin and melatonin might exhibit an effective therapeutic option in bladder cancer therapy.

Impact of tumor architecture on disease recurrence and cancer-specific mortality of upper tract urothelial carcinoma treated with radical nephroureterectomy.

Upper tract urinary carcinoma (UTUC) is a relatively uncommon but aggressive disease. Recent publications have assessed the prognostic significance of tumor architecture in UTUC, but there is still controversy regarding the significance and importance of tumor architecture on disease recurrence. We retrospectively reviewed the medical records of 101 patients with clinical UTUC who had undergone surgery. Univariate and multivariate analyses were conducted to identify factors associated with disease recurrence and cancer-specific mortality. As our single center study and the limited sample size may influence the clinical significance, we further quantitatively combined the results with those of existing published literature through a meta-analysis compiled from searching several databases. At a median follow-up of 41.3 months, 25 patients experienced disease recurrence. Spearman's correlation analysis showed that tumor architecture was found to be positively correlated with the tumor location and the histological grade. Kaplan-Meier curves showed that patients with sessile tumor architecture had significantly poor recurrence free survival (RFS) and cancer specific survival (CSS). Furthermore, multivariate analysis suggested that tumor architecture was independent prognostic factors for RFS (Hazard ratio, HR = 2.648) and CSS (HR = 2.072) in UTUC patients. A meta-analysis of investigating tumor architecture and its effects on UTUC prognosis was conducted. After searching PubMed, Medline, Embase, Cochrane Library and Scopus databases, 17 articles met the eligibility criteria for this analysis. The eligible studies included a total of 14,368 patients and combined results showed that sessile tumor architecture was associated with both disease recurrence with a pooled HR estimate of 1.454 and cancer-specific mortality with a pooled HR estimate of 1.416. Tumor architecture is an independent predictor for disease recurrence after radical nephroureterectomy for UTUC. Therefore, closer surveillance is necessary, especially in patients with sessile tumor architecture.

The effects of body mass index on spirometry tests among adults in Xi'an, China.

Obese people have higher risk of respiratory symptoms. The relationship between obesity and lung function varies with age, race, and geographical region. The objective of this study is to examine the effects of body mass index on spirometric tests among adults in Xi'an city.This is a cross-sectional study. Pulmonary function testing was conducted on participants recruited from Xi'an, China between July and August 2012. Force expiratory volume in first second (FEV1), force vital capacity (FVC), FEV1/FVC, peak expiratory flow (PEF), and forced expiratory flow at 25-75% (FEF25-75) were measured by portable Spirometer. Lung function was analyzed according to Chinese standard of general obesity.A total of 770 subjects were analyzed in this study, of whom 299 were males and 471 were females. FVC% (P = .037) decreased significantly in obese subjects than in nonobese subjects. FVC% (P = .02) declined significantly in overweight subjects than in normal subjects. For smoker, FEV1% (P = .03) and FVC% (P = .02) were lower notably in overweight subjects than in normal subjects. FEV1% (P = .0008), FVC% (P = .0004), and PEF% (P < .0001) were higher significantly in normal subjects than in underweight subjects.FVC notably decreased in obese people, not FEV1, FEV1/FVC, PEF, and FEF25-75. FEV1, FVC, and PEF were higher significantly in normal subjects than in underweight subjects. FVC is affected by BMI in diphasic change.

[Nasal endoscope surgery of acinic cell carcinoma of salivary gland on nasal septum: a case report].

A 67-year-old male patient was admitted because of "the right side nasal obstruction repeatedly for 4 years". He got nasal obstruction 4 years ago, especially for the right side nasal cavity, sometimes got blood in his nasal discharge, then the symptom relieved after accepting treatment in local hospital. During the 4 years, the symptom repeatedly occurrence. Three days before hospitalization, the CT examination indicated abnormal things in his nasal cavity and the bone of his nasal sinus had been destroyed. Some abnormal organism were sent to pathological examination, and the report indicated it is acinic cell carcinoma of salivary gland. During the nasal endoscope surgery, a red goiter was found in his nose with its surface crude and brittle. Then we cut the goiter by nasal endoscope, during the operation we find the bottom of the goiter is on the nasal septum. Two weeks after the operation, the patient received the radiation therapy. One year after the operation he doesn't get the abnormal symptom and the nasal MRI not found recidivation.

MiR-21 modulates human airway smooth muscle cell proliferation and migration in asthma through regulation of PTEN expression.

BACKGROUND: Asthma is characterized by airway remodeling arising from an increase in airway smooth muscle (ASM) mass. This increase is regulated in part by ASM cell proliferation and migration. MicroRNA (miR)-21 also plays a role in asthma, but the molecular mechanisms underlying its effects are not completely understood. This study investigated the effects and mechanism of miR-21 on the human ASM (HASM) cell proliferation and migration. MATERIALS AND METHODS: HASM cells were transduced with a miR-21 vector, and the expression of miR-21 was determined by quantitative real-time polymerase chain reaction (qRT-PCR). The effect of the miR-21 on HASM cell proliferation and migration was analyzed by CCK8 and transwell assay. The expression level of PTEN (phosphatase and tensin homolog deleted on chromosome 10) in HASM cells was assessed by qRT-PCR and Western blot analysis. Meanwhile, the activity of PTEN was measured by PTEN malachite green assay kit. RESULTS: Lentivirus-mediated miR-21 overexpression markedly enhanced the proliferation and migration of HASM cells (P < .05), and ablation of miR-21 by anti-miR-21 inhibitor markedly reduced cell proliferation and migration. We demonstrated that miR-21 overexpression significantly reduced the expression of PTEN (P < .05), while PTEN knock-down markedly increased HASM cell proliferation and migration. Furthermore, we found that overexpression of PTEN led to a decrease of HASM cell proliferation and migration. MiR-21 mediated HASM cell proliferation and migration through activation of the phosphoinositide 3-kinase pathway. CONCLUSIONS: This study provides the first in vitro evidence that overexpression of miR-21 in HASM cells can trigger cell proliferation and migration, and the effects of miR-21 depend on the level of PTEN.

MiR-138 suppresses airway smooth muscle cell proliferation through the PI3K/AKT signaling pathway by targeting PDK1.

BACKGROUND: Airway smooth muscle cells (ASMCs) play important physiological roles in the lung, and their abnormal proliferation directly contributes to airway remodeling during development of lung diseases such as asthma. MicroRNAs are small yet versatile gene tuners that regulate a variety of cellular processes, including cell growth and proliferation, but little is known about the precise role of microRNAs in the proliferation of ASMCs. METHODS: In this study, human ASMCs from asthmatic and non-asthmatic donors were used. MicroRNA and mRNA expression were measured by quantitative real-time PCR. Dual-luciferase reporter assays were performed to determine whether microRNA-138 (miR-138) binds directly to 3-phosphoinositide-dependent protein kinase-1(PDK1) 3' untranslated region (3'-UTR) to alter gene expression. RESULTS: The results showed that overexpression of miR-138 reduced proliferation of human ASMCs, whereas inhibition of miR-138 increased proliferation of ASMCs. MiR-138 directly suppressed PDK1 expression by targeting the 3'-UTR of the gene. MiR-138 controls ASMC proliferation through directly inhibiting the phosphoinositide 3-kinase (PI3K) pathway. CONCLUSIONS: Our study indicated that miR-138 regulation of PI3K signaling in ASMCs by altering the expression of PDK1 can have a profound impact on cell proliferation.

[Significance and expression of VEGF and its receptor in nasal inverted papillomas and the correlation with malignant phenotype].

OBJECTIVE: To determine the expression of vascular endothelial growth factor (VEGF) and their receptor in nasal inverted papillomas (NIP) and to clarify the function of VEGF in the occurrence of NIPs and the correlation with malignant phenotype. METHOD: VEGF and its receptor (flk-1), expression were examined by immunohistochemistry using LSAB method in sections of NIP from 48 patients and squamous carcinoma from 8 patients. RESULT: All the epithelium together with the adjacent vascular and stroma,expressed increased positive staining of VEGF and flk-1 with the degree of atypical hyperplasia in epithelium. The VEGF/flk-1 expression in epithelium was significantly stronger in severe atypical hyperplasia than that in mild atypical hyperplasia, and same in mild atypical hyperplasia than in NIPs (P<0.01). CONCLUSION: VEGF/flk-1 participate in the growth of NIPs. The enhanced VEGF/flk-1 in the epithelium may be identified as one of the parameters in judging malignant transformation of NIPs.