miR-212/132 attenuates OVA-induced airway inflammation by inhibiting mast cells activation through MRGPRX2 and ASAP1.

Allergic asthma is a chronic inflammatory disease of airways involving complex mechanisms, including MAS-related GPR family member X2 (MRGPRX2) and its orthologue MRGPRB2 on mast cells (MCs). Although miRNAs have been previously shown to related to allergic asthma, the role of miR-212/132 in this process has not been studied. In this study, the predicted pairing of miRNAs and MRGPRX2 (MRGPRB2) mRNAs was carried out by online databases and the function was verify using in vivo and in vitro experiments. Database prediction showed that miR-212/132 interact with MRGPRX2 and MRGPRB2. miR-212/132 mimics alleviated MRGPRB2 mRNA expression as well as pathology changes in lungs and AHR of mice with airway inflammation in vivo. The expression level of MRGPRB2 in the mice lungs after inhaled OVA was also decreased by miR-212/132 mimics. Meanwhile, miR-212/132 inhibited MCs degranulation and cytokines release triggered by C48/80 in vitro. Further, ASAP1 (ARF GTPase-Activating Protein 1) was selected from the junction related pathways using RNAseq and KEGG enrichment. ASAP1 mRNA level was upregulated in airway inflammation and MCs activation and decreased by miR-212/132 mimics. miR-212/132 attenuated OVA-induced airway inflammation by inhibiting MCs activation through MRGPRX2 and ASAP1.

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.

Lactobacillus rhamnosus 76 alleviates airway inflammation in ovalbumin-allergic mice and improves mucus secretion by down-regulating STAT6/SPDEF pathway.

Previous studies have reported a correlation between the dysregulation of intestinal microbiota and the occurrence of asthma. This study aimed to investigate the effect of probiotic Lactobacillus rhamnosus 76 (LR76) on ovalbumin (OVA)-allergic mice and the mechanism of LR76 affecting mucus secretion in asthma. OVA-allergic mice were supplemented with LR76, and 16HBE cells induced by interleukin-13 (IL-13) were treated with LR76 supernatant (LR76-s) to observe the effect of LR76. In OVA-sensitized mice, LR76 alleviated the inflammatory cell infiltration in lung tissue and reduced the inflammatory cell counts of BALF. The expression level of mRNA, including Il4, Il5, Il13, Il25, Tgfb1, Il10, and Ifng, was decreased in the lung tissue of mice in the LR76 group compared with the OVA group. MUC5AC expression was down-regulated, while SCGB1A1 was up-regulated in the lung tissue of OVA-allergic mice after being supplemented with LR76 and in 16HBE cells induced by IL-13 after incubating with LR76-s. LR76 and LR76-s down-regulated the expression of proteins, including STAT6, p-STAT6, and SPDEF, and mRNA of STAT6 and SPDEF. In conclusion, LR76 alleviated airway inflammation and Th2 response in OVA-allergic mice and improved the mucus secretion of mouse lung tissue and 16HBE cells in the asthma model by down-regulating STAT6/SPDEF pathway.

Fluid-solid coupling model and biological features of large vestibular aqueduct syndrome.

Objective: Computed tomography (CT) images of the temporal bone of large vestibular aqueduct syndrome (LVAS) patients were used to establish 3D numerical models based on the structure of the inner ear, which are, in turn, used to construct inner ear fluid-solid coupling models. The physiological features and pathophysiology of LVAS were analyzed from a biomechanical perspective using finite element analysis. Methods: CT images of the temporal bone were collected from five children attending the Second Hospital of Dalian Medical University in 2022. The CT images were used to build 3D models of the inner ear containing the vestibular aqueduct (VA) by Mimics and Geomagic software, and round window membrane models and fluid-solid coupling models were built by ANSYS software to perform fluid-solid coupling analysis. Results: By applying different pressure loads, the deformation of the round window membranes occurred, and their trend was basically the same as that of the load. The deformation and stress of the round window membranes increased with the increase in load. Under the same load, the deformation and stress of the round window membranes increased with the expansion of the midpoint width of the VA. Conclusion: CT images of the temporal bone used clinically could establish a complete 3D numerical model of the inner ear containing VA. Fluctuations in cerebrospinal fluid pressure could affect inner ear pressure, and VA had a limiting effect on the pressure from cerebrospinal fluid. The larger the VA, the smaller the limiting effect on the pressure.

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.

Donepezil ameliorates oxygen­glucose deprivation/reoxygenation­induced cardiac microvascular endothelial cell dysfunction through PARP1/NF­κB signaling.

Ischemia/reperfusion (I/R) injury is a serious clinical condition characterized by high morbidity and mortality rates. Donepezil plays a neuroprotective role in I/R­associated diseases. The aim of the present study was to investigate the role and the potential mechanism of action of donepezil in I/R­induced myocardial microvascular endothelial cell dysfunction. An I/R model was simulated using oxygen­glucose deprivation/reoxygenation (OGD/R) injury in human cardiac microvascular endothelial cells (CMECs). Cell viability and lactate dehydrogenase release were examined following treatment with donepezil. Commercial kits were used to evaluate cell apoptosis, cell permeability and caspase­3 activity. The expression levels of apoptosis­associated proteins, as well as proteins found in tight junctions or involved in the poly(ADP­ribose) polymerase 1 (PARP1)/NF­κB pathway, were measured using western blotting. These parameters were also examined following PARP1 overexpression. The results demonstrated that donepezil increased cell viability and reduced toxicity in OGD/R­treated CMECs. The apoptotic rate, caspase­3 activity and protein expression levels of Bax and cleaved caspase­3 were significantly reduced following donepezil treatment, which was accompanied by Bcl­2 upregulation. Moreover, cell permeability was notably reduced, coupled with a marked increase in the expression of tight junction­associated proteins. The expression levels of proteins related to PARP1/NF­κB signaling were significantly downregulated in CMECs following donepezil treatment. However, the protective effects of donepezil on OGD/R­induced CMEC injury were reversed following PARP1 overexpression. In conclusion, donepezil suppressed OGD/R­induced CMEC dysfunction via PARP1/NF­κB signaling. This finding provided insight into the mechanism underlying myocardial I/R injury.

Substance P-induced lung inflammation in mice is mast cell dependent.

BACKGROUND: Allergic asthma is a common inflammatory lung disease and a major health problem worldwide. Mast cells (MCs) play a key role in the early-stage pathophysiology of allergic asthma. Substance P (SP) functions in neurogenic inflammation by activating MCs, and therefore, it may to participate in the occurrence and development of asthma. OBJECTIVE: We examined the relationship between SP and lung inflammation, and also whether SP can directly trigger asthma. METHODS: We measured the number of peripheral blood eosinophils, neutrophils and basophils and evaluated the levels of IgE and SP in blood samples of 86 individuals with allergic asthma. Serum IgE and SP levels were also determined in 29 healthy individuals. C57BL/6 mice were subjected to different doses of SP, and bronchoalveolar lavage fluid (BALF) was collected to count the inflammatory cells. Lung tissues were analysed using histopathological methods to evaluate lung peribronchial inflammation, fibrosis and glycogen deposition. Levels of IgE, interleukin (IL)-1, IL-2, IL-4, IL-5, IL-13, IL-17 and IFN-γ were determined in mouse serum. RESULTS: Substance P levels were increased in the serum samples of patients with asthma. SP induced mouse lung peribronchial inflammation, fibrosis and glycogen deposition, with high levels of Th2-related cytokines such as IL-4, IL-5 and IL-13 observed in the BALF. Furthermore, low level of total IgE was noted in the serum, and SP had little effect on MC-deficient kitW-sh/W-sh mice. CONCLUSIONS & CLINICAL RELEVANCE: Substance P levels increased significantly in serum of asthmatic patients and independently associated with the risk of asthma. Furthermore, SP induced Th2 lung inflammation in mice, which was dependent on MCs.

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.

News on alginate recovery by forward osmosis: Reverse solute diffusion is useful.

The water content in the recycled alginate solutions from aerobic granular sludge was nearly 100%. Forward osmosis (FO) has become an innovative dewatering technology. In this study, the FO concentration of sodium alginate (SA) was investigated using calcium chloride as a draw solute. The reverse solute flux (RSF) of calcium ions in FO had a beneficial effect, contrary to the findings of previous literature. The properties of the concentrated substances formed on the FO membrane on the feed side were analyzed by Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy, verifying that calcium alginate (Ca-Alg), which can be used as a recycled material, was formed on the FO membrane on the feed side owing to the interaction between SA and permeable calcium ions. Water flux increased significantly with the increase in calcium chloride concentration, while the concentration of SA had little influence on the water flux in FO. Based on this discovery, we propose a novel method for the concentration and recovery of alginate, in which the RSF of calcium ions is utilized for recovering Ca-Alg by FO, with calcium chloride as a draw solute.

Study of the biomechanical mechanisms of benign paroxysmal positional vertigo.

From a biomechanical point of view, the process of Benign paroxysmal positional vertigo (BPPV) includes 2 fluid¯solid coupling effects: the interaction between particles and endolymph and the interaction between endolymph and cupula. The interaction between the canaliths and the wall would affect the coupling effects. This study aimed to investigate the entire process of cupula motion caused by canaliths motion and the influence of canalith particles composition. A biomechanical numerical model was established to simulate the canalith falling process and study the influence of canalith diameter, number, and initial falling position on cupula movement. Simultaneously, the relationship between cupula displacement and the nystagmus signal was analyzed in BPPV patients. The results revealed that the particle velocity was proportional to the particle diameter. The pressure difference between the two sides of the cupula was directly proportional to the canalith diameter and number. The degree of vertigo was positively related to the slow angular velocity of the nystagmus and, therefore, reflected canalith number and diameter. The BPPV latent period and vertigo duration were inversely related to particle diameter. Thus, the number of particles, particle radius, and initial falling position affected cupula movement, which was reflected in the nystagmus.

The biomechanical characteristics of human vestibular aqueduct: a numerical-based model construction and simulation.

Vestibular aqueduct is a precise structure embedded in the temporal bone and plays a key role in the physiological function of inner ear by maintaining the endolymphatic circulation and buffering the impact from intracranial pressure. Although the alterations on the morphology or volume of vestibular aqueduct result in variety of diseases, the approaches of evaluating the condition of vestibular aqueduct are still unsatisfing because the pathological sections utilized for the 3D construction model most likely undergoes morphological changes. In this study, the vestibular aqueduct images obtained by CT scanning were processed by finite element method to construct the 3D model. To assess if this numerical model reflects the actual biomechanical properties of vestibular aqueduct, the fluid-solid coupling calculation was applied to simulate the endolymphatic flow in the vestibular aqueduct. By measuring the dynamics of endolymphatic flow, and the pressure and displacement on round membrane under external pressure, we found the numerical 3D model recapitulated the biomechanical characteristics of the real vestibular aqueduct. In summary, our approach of 3D model construction for vestibular aqueduct will provide a powerful method for the research of vestibular aqueduct-related diseases.

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.

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.

Suppression of sirtuin 1 alleviates airway inflammation through mTOR­mediated autophagy.

Sirtuin 1 (SIRT1) is involved in the pathogenesis of allergic asthma. This study aimed to investigate whether EX­527, a specific SIRT1 inhibitor, exerted suppressive effects on allergic airway inflammation in mice submitted to ovalbumin (OVA) inhalation. In addition, this study assessed whether such a protective role was mediated by autophagy suppression though mammalian target of rapamycin (mTOR) activation. Female C57BL/6 mice were sensitized to OVA and EX­527 (10 mg/kg) was administered prior to OVA challenge. The study found that EX­527 reversed OVA­induced airway inflammation, and reduced OVA­induced increases in inflammatory cytokine expression, and total cell and eosinophil counts in bronchoalveolar lavage fluid. In addition, EX­527 enhanced mTOR activation, thereby suppressing autophagy in allergic mice. To assess whether EX­527 inhibited airway inflammation in asthma through the mTOR­mediated autophagy pathway, rapamycin was administered to mice treated with EX­527 after OVA sensitization. All effects induced by EX­527, including increased phosphorylated­mTOR and decreased autophagy, were abrogated by rapamycin treatment. Taken together, the present findings indicated that EX­527 may inhibit allergic airway inflammation by suppressing autophagy, an effect mediated by mTOR activation in allergic mice.

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.