Preparation, characterization, and in vitro/vivo evaluation of a multifunctional electrode coating for cochlear implants.

Cochlear implantation (CI) is the primary intervention for patients with sensorineural hearing loss to restore their hearing. However, approximately 90 % of CI recipients experience unexpected fibrosis around the inserted electrode arrays due to acute and chronic inflammation. This fibrosis leads to progressive residual hearing loss. Addressing this complication is crucial for enhancing CI outcomes, yet an effective treatment has not yet been found. In this study, we developed a multifunctional dexamethasone (DXM)-loaded polytrimethylene carbonate (PTMC) electrode coating to mitigate inflammatory reactions and fibrosis after CI. This thin and flexible coating could preserve the mechanical performance of the electrode and reduce the implantation resistance for CI. The in vitro release studies demonstrated the DXM-PTMC coating's efficient drug loading and sustained release capability over 90 days. DXM-PTMC also showed long-term stability, high biocompatibility, and effective anti-inflammatory effects in vitro and in vivo. Compared with the uncoated group, DXM-PTMC coating significantly inhibited the expression of inflammatory factors, such as NO, TNF-α, IL-1ß, and IL-6. DXM-PTMC coating suppressed fibrosis in rat implantation models for 3 weeks by reducing both acute and chronic inflammation. Our findings suggest that DXM-PTMC coating is a novel strategy to improve the outcomes of CI.

Zwitterion modified cochlear implants resist postoperative infection and inflammation.

The cochlear implant (CI), an advanced electronic device replacing the entire cochlear function, is the ultimate treatment for over 466 million people with disabling hearing loss. Infection after cochlear implantation is a common and worrisome complication despite the routine administration of the antibiotic. The bacterial biofilms formed on the surface of CI are the main cause of antibiotic failure. To solve this problem, we developed a copper-containing zwitterionic coating consisting of anti-adherent poly sulfobetaine methacrylate (PSB) and steadfast polydopamine (PDA). CuSO4/H2O2. was added to accelerate this co-deposition reaction and enhance the anti-bacterial property. The preparation method was simple, rapid, and suitable for clinical use. In our in vitro and in vivo studies, the PSB/PDA(Cu) coating showed high biocompatibility, and conferred CI implants excellent anti-inflammatory, strong anti-bacterial effects, and great anti-biofilm properties to representative Gram-positive and Gram-negative bacteria. These findings implied that the PSB/PDA(Cu) coating was a unique anti-bacterial strategy for enhancing CI performance.

A hub gene signature as a therapeutic target and biomarker for sepsis and geriatric sepsis-induced ARDS concomitant with COVID-19 infection.

Background: COVID-19 and sepsis represent formidable public health challenges, characterized by incompletely elucidated molecular mechanisms. Elucidating the interplay between COVID-19 and sepsis, particularly in geriatric patients suffering from sepsis-induced acute respiratory distress syndrome (ARDS), is of paramount importance for identifying potential therapeutic interventions to mitigate hospitalization and mortality risks. Methods: We employed bioinformatics and systems biology approaches to identify hub genes, shared pathways, molecular biomarkers, and candidate therapeutics for managing sepsis and sepsis-induced ARDS in the context of COVID-19 infection, as well as co-existing or sequentially occurring infections. We corroborated these hub genes utilizing murine sepsis-ARDS models and blood samples derived from geriatric patients afflicted by sepsis-induced ARDS. Results: Our investigation revealed 189 differentially expressed genes (DEGs) shared among COVID-19 and sepsis datasets. We constructed a protein-protein interaction network, unearthing pivotal hub genes and modules. Notably, nine hub genes displayed significant alterations and correlations with critical inflammatory mediators of pulmonary injury in murine septic lungs. Simultaneously, 12 displayed significant changes and correlations with a neutrophil-recruiting chemokine in geriatric patients with sepsis-induced ARDS. Of these, six hub genes (CD247, CD2, CD40LG, KLRB1, LCN2, RETN) showed significant alterations across COVID-19, sepsis, and geriatric sepsis-induced ARDS. Our single-cell RNA sequencing analysis of hub genes across diverse immune cell types furnished insights into disease pathogenesis. Functional analysis underscored the interconnection between sepsis/sepsis-ARDS and COVID-19, enabling us to pinpoint potential therapeutic targets, transcription factor-gene interactions, DEG-microRNA co-regulatory networks, and prospective drug and chemical compound interactions involving hub genes. Conclusion: Our investigation offers potential therapeutic targets/biomarkers, sheds light on the immune response in geriatric patients with sepsis-induced ARDS, emphasizes the association between sepsis/sepsis-ARDS and COVID-19, and proposes prospective alternative pathways for targeted therapeutic interventions.

B-cell-derived IL-10 promotes allergic sensitization in asthma regulated by Bcl-3.

Aeroallergen sensitization, mainly mediated by lung epithelium and dendritic cells (DCs), is integral to allergic asthma pathogenesis and progression. IL-10 has a dual role in immune responses, as it inhibits myeloid cell activation but promotes B-cell responses and epithelial cell proliferation. Here, we report a proinflammatory function of B-cell-derived IL-10 modulated by Bcl-3 in allergic asthma. Specifically, Bcl-3-/- mice showed elevated IL-10 levels and were found to be highly vulnerable to allergic asthma induced by house dust mites (HDMs). IL-10 had a positive correlation with the levels of the DC chemoattractant CCL-20 in HDM-sensitized mice and in patients with asthma and induced a selective increase in CCL-20 production by mouse lung epithelial cells. Blockade of IL-10 or IL-10 receptors during sensitization dampened both HDM-induced sensitization and asthma development. IL-10 levels peaked 4 h post sensitization with HDM and IL-10 was primarily produced by B cells under Bcl-3-Blimp-1-Bcl-6 regulation. Mice lacking B-cell-derived IL-10 displayed decreased lung epithelial CCL-20 production and diminished DC recruitment to the lungs upon HDM sensitization, thereby demonstrating resistance to HDM-induced asthma. Moreover, responses to HDM stimulation in Bcl-3-/- mice lacking B-cell-derived IL-10 were comparable to those in Bcl-3+/+ mice. The results revealed an unexpected role of B-cell-derived IL-10 in promoting allergic sensitization and demonstrated that Bcl-3 prevents HDM-induced asthma by inhibiting B-cell-derived IL-10 production. Thus, targeting the Bcl-3/IL-10 axis to inhibit allergic sensitization is a promising approach for treating allergic asthma. IL-10 is released rapidly from lung plasma cells under Bcl-3-Blimp-1-Bcl-6 regulation upon house dust mite exposure and amplifies lung epithelial cell (EC)-derived CCL-20 production and subsequent dendritic cell (DC) recruitment to promote allergic sensitization in asthma.

B cell-derived IL-10 promotes the resolution of lipopolysaccharide-induced acute lung injury.

Inflammation resolution is critical for acute lung injury (ALI) recovery. Interleukin (IL)-10 is a potent anti-inflammatory factor. However, its role in ALI resolution remains unclear. We investigated the effects of IL-10 during the ALI resolution process in a murine lipopolysaccharide (LPS)-induced ALI model. Blockade of IL-10 signaling aggravates LPS-induced lung injury, as manifested by elevated pro-inflammatory factors production and increased neutrophils recruitment to the lung. Thereafter, we used IL-10 GFP reporter mice to discern the source cell of IL-10 during ALI. We found that IL-10 is predominantly generated by B cells during the ALI recovery process. Furthermore, we used IL-10-specific loss in B-cell mice to elucidate the effect of B-cell-derived IL-10 on the ALI resolution process. IL-10-specific loss in B cells leads to increased pro-inflammatory cytokine expression, persistent leukocyte infiltration, and prolonged alveolar barrier damage. Mechanistically, B cell-derived IL-10 inhibits the activation and recruitment of macrophages and downregulates the production of chemokine KC that recruits neutrophils to the lung. Moreover, we found that IL-10 deletion in B cells leads to alterations in the cGMP-PKG signaling pathway. In addition, an exogenous supply of IL-10 promotes recovery from LPS-induced ALI, and IL-10-secreting B cells are present in sepsis-related ARDS. This study highlights that B cell-derived IL-10 is critical for the resolution of LPS-induced ALI and may serve as a potential therapeutic target.

Integrative bioinformatics and validation studies reveal KDM6B and its associated molecules as crucial modulators in Idiopathic Pulmonary Fibrosis.

Background: Idiopathic Pulmonary Fibrosis (IPF) can be described as a debilitating lung disease that is characterized by the complex interactions between various immune cell types and signaling pathways. Chromatin-modifying enzymes are significantly involved in regulating gene expression during immune cell development, yet their role in IPF is not well understood. Methods: In this study, differential gene expression analysis and chromatin-modifying enzyme-related gene data were conducted to identify hub genes, common pathways, immune cell infiltration, and potential drug targets for IPF. Additionally, a murine model was employed for investigating the expression levels of candidate hub genes and determining the infiltration of different immune cells in IPF. Results: We identified 33 differentially expressed genes associated with chromatin-modifying enzymes. Enrichment analyses of these genes demonstrated a strong association with histone lysine demethylation, Sin3-type complexes, and protein demethylase activity. Protein-protein interaction network analysis further highlighted six hub genes, specifically KDM6B, KDM5A, SETD7, SUZ12, HDAC2, and CHD4. Notably, KDM6B expression was significantly increased in the lungs of bleomycin-induced pulmonary fibrosis mice, showing a positive correlation with fibronectin and α-SMA, two essential indicators of pulmonary fibrosis. Moreover, we established a diagnostic model for IPF focusing on KDM6B and we also identified 10 potential therapeutic drugs targeting KDM6B for IPF treatment. Conclusion: Our findings suggest that molecules related to chromatin-modifying enzymes, primarily KDM6B, play a critical role in the pathogenesis and progression of IPF.

Zwitterionic Polymer/Polydopamine Coating of Electrode Arrays Reduces Fibrosis and Residual Hearing Loss after Cochlear Implantation.

Since the first surgery 50 years ago, cochlear implantation (CI) is the major treatment for patients with severe sensorineural hearing loss. However, unexpected foreign body reactions (FBRs) after surgery are reported in 90% of CI recipients, resulting in the formation of fibrosis in the cochlea and progressive residual hearing loss. Zwitterion modification is universally used to reduce bio-fouling and suppress FBRs but never for CI. In the present study, a zwitterionic coating is developed, which is composed of poly sulfobetaine methacrylate (PSB) and polydopamine (PDA) for cochlear implants. The PSB-PDA coating shows a series of characters for an ideal anti-FBRs material, including super-hydrophilicity, low protein and cell adsorption, long-term stability, and high biocompatibility. Compared to the uncoated controls, PSB-PDA coating inhibits the activation of macrophages and reduces the release of inflammatory factors (TNF-α, IL-1ß, NO) and fibrosis-related factors (TGF-ß1, α-SMA, collagen I). PSB-PDA coated electrode arrays suppress fibrosis completely and preserve residual hearing significantly in rat CI models. These results suggest that PSB-PDA coating is a novel strategy for anti-fibrosis to improve the outcomes of CI.

Nomograms predict survival benefits of radical prostatectomy and chemotherapy for prostate cancer with bone metastases: A SEER-based study.

Purpose: This study aimed to identify independent prognosis-associated factors of bone-metastatic prostate cancer. The nomograms were further developed to obtain indicators for the prognostic evaluation. Methods: A total of 7315 bone-metastatic prostate cancer (PCa) patients from 2010 to 2016 were retrospectively collected from the Surveillance, Epidemiology, and End Results (SEER) database. Patients were randomly divided into the training cohort (n=5,120) and test cohort (n=2,195) in a ratio of 7:3. Univariate and multivariate Cox regression models were applied to evaluate potential risk factors. A 1:1 propensity score matching (PSM) was further performed to decrease the confounding effect and re-evaluate the influence of radical prostatectomy and chemotherapy on prognosis. Combining these potential prognosis factors, the nomograms of cancer-specific survival (CSS) and overall survival (OS) at different times were established. C-indexes, calibration curves, and decision curves were developed to evaluate the discrimination, calibration, and clinical benefit of the nomograms. Results: Eleven independent prognosis factors for CSS and twelve for OS were utilized to conduct the nomograms respectively. The C-indexes of nomograms for CSS and OS were 0.712 and 0.702, respectively. A favorable consistency between the predicted and actual survival probabilities was demonstrated by adopting calibration curves. Decision curves also exhibited a positive clinical benefit of the nomograms. Conclusions: Nomograms were formulated successfully to predict 3-year and 5-year CSS and OS for bone-metastatic PCa patients. Radical prostatectomy and chemotherapy were strongly associated with the bone-metastatic PCa prognosis.

Bioinformatics and systems-biology analysis to determine the effects of Coronavirus disease 2019 on patients with allergic asthma.

Background: The coronavirus disease (COVID-19) pandemic has posed a significant challenge for global health systems. Increasing evidence shows that asthma phenotypes and comorbidities are major risk factors for COVID-19 symptom severity. However, the molecular mechanisms underlying the association between COVID-19 and asthma are poorly understood. Therefore, we conducted bioinformatics and systems biology analysis to identify common pathways and molecular biomarkers in patients with COVID-19 and asthma, as well as potential molecular mechanisms and candidate drugs for treating patients with both COVID-19 and asthma. Methods: Two sets of differentially expressed genes (DEGs) from the GSE171110 and GSE143192 datasets were intersected to identify common hub genes, shared pathways, and candidate drugs. In addition, murine models were utilized to explore the expression levels and associations of the hub genes in asthma and lung inflammation/injury. Results: We discovered 157 common DEGs between the asthma and COVID-19 datasets. A protein-protein-interaction network was built using various combinatorial statistical approaches and bioinformatics tools, which revealed several hub genes and critical modules. Six of the hub genes were markedly elevated in murine asthmatic lungs and were positively associated with IL-5, IL-13 and MUC5AC, which are the key mediators of allergic asthma. Gene Ontology and pathway analysis revealed common associations between asthma and COVID-19 progression. Finally, we identified transcription factor-gene interactions, DEG-microRNA coregulatory networks, and potential drug and chemical-compound interactions using the hub genes. Conclusion: We identified the top 15 hub genes that can be used as novel biomarkers of COVID-19 and asthma and discovered several promising candidate drugs that might be helpful for treating patients with COVID-19 and asthma.

Mesoporous silica nanoparticle-modified electrode arrays of cochlear implants for delivery of siRNA-TGFß1 into the inner ear.

Cochlear implants (CI) are widely used in patients to restore hearing function. Uncontrolled fibrosis in the cochleae induced by excess secretion of TGFß1 seriously affects the effectiveness of CIs. siRNA is a potential therapeutic strategy to downregulate TGFß1 specifically. However, treatment with siRNA in cochleae is difficult due to the poor penetration capability and instability of siRNA and the inaccessibility and vulnerability of cochleae. To address these challenges, we developed amino-functionalized mesoporous silica nanoparticle (MSN-NH2)-modified electrode arrays to deliver siRNA-TGFß1 into the inner ear. The shape, diameter, pore diameter, and zeta potential of MSN-NH2 were investigated. siRNA loading capability and protective effect of MSN-NH2 were determined by agarose gel electrophoresis assay. The cytotoxicity, cellular uptake assay, and TGFß1 knockdown efficiency of MSN-NH2 were studied by CCK-8 assay, flow cytometry, and real-time PCR, respectively. MSN-NH2-siTGFß1 nanoparticles were absorbed into the electrode arrays and worked in the cochleae. MSN-NH2-siTGFß1-modified CI electrode arrays may be an attractive therapeutic clinical intervention strategy to inhibit cochlear implantation fibrosis.

In vitro and vivo study of tranilast protects from acute respiratory distress syndrome and early pulmonary fibrosis induced by smoke inhalation.

BACKGROUND: Tranilast (N-[3＇,4＇-dimethoxycinnamoyl]-anthranilic acid) is an analog of a tryptophan metabolite. It was identified with anti-inflammatory and antifibrotic activities, and used in the treatment of a variety of diseases, such as anti - allergy, bronchial asthma, and hypertrophic scars. As a drug with few adverse reactions, tranilast has attracted great attention, but its application is limited due to the uncertainty of dosages and mechanisms. In this study, the protection effects of different doses of tranilast on smoke inhalation mediated lung injury on rats, and on the damage of three kinds of lung cells in vitro were investigated. METHOD: In vivo, Sprague-Dawley rats were randomly divided into sham group, smoke group (rats were exposed to pine sawdust smoke three times, each time for 5 min), different doses of tranilast treatment group (doses were 100 mg/kg, 200 mg/kg and 300 mg/kg, ip.) and placebo group. After 1, 3 and 7 days, pulmonary function, pathologic injury by HE staining, cytokines and oxidative stress level by kits were determined. At 7days, lung fibrosis was assessed by Masson's trichrome staining and the level of hydroxyproline (HYP). In vitro, three kinds of lung cells from normal rats were isolated: type II alveolar epithelial cells (AT-II), pulmonary microvascular endothelial cells (PMVECs) and pulmonary fibroblasts (PFs). To investigate the potential effects of tranilast on cell proliferation, cell cycle and cytokine production of three kinds of lung cells exposed to smoke. RESULTS: Compared with smoke group and placebo group, tranilast treatment significantly reduced histopathological changes (such as pulmonary hemorrhage, edema and inflammatory cell infiltration, etc.), significantly reduced histopathological score (p < 0.05), increased arterial oxygen partial pressure, and decreased the levels of IL-1ß, TNF-α, TGF-ß1 (p < 0.05), oxidative stress and the expression of nuclear transcription factor κB (NF-κB) smoke exposed rats (p < 0.01). In particular, the effect of 200 mg/kg dose was more prominent. In vitro, smoke induced AT-II and PMVECs apoptosis, improved PFs proliferation (p < 0.01), activity of SOD and decreased the content of MDA (p < 0.01). However, tranilast seems to be turning this trend well. The inflammatory factor IL-11ß, TNF-α and TGF-ß1, and the expression of NF-κB were significantly lower in the tranilast treatment than in the smoke group (p < 0.01). CONCLUSION: This study indicates that tranilast had a protective effect on acute respiratory distress syndrome and early pulmonary fibrosis of rats in vivo. In addition, tranilast promotes proliferation of AT-II and PMVECs but inhibits PFs proliferation, down-regulates secretion of inflammatory cytokines and alleviates oxidative stress of AT-II, PMVECs and PFs after smoke stimuli in vitro.

Long-Term Release of Dexamethasone With a Polycaprolactone-Coated Electrode Alleviates Fibrosis in Cochlear Implantation.

Cochlear implantation (CI) is the major treatment for severe sensorineural hearing loss. However, the fibrotic tissue forming around the electrodes reduces the treatment effectiveness of CI. Dexamethasone (DEX) is usually applied routinely in perioperative treatment of cochlear implantation (CI), but its diffusion in the inner ear after systemic administration is limited. In the present study, an electrode coated with polycaprolactone (PCL) loaded with dexamethasone was developed with a simple preparation process to maintain the stability of the electrode itself. The DEX-loaded PCL coating has good biocompatibility and does not change the smoothness, flexibility, or compliance of the implant electrode. Stable and effective DEX concentrations were maintained for more than 9 months. Compared with the pristine electrode, decreasing intracochlear fibrosis, protection of hair cells and spiral ganglion cells, and better residual hearing were observed 5 weeks after PCL-DEX electrode implantation. The PCL-DEX electrode has great potential in preventing hearing loss and fibrosis by regulating macrophages and inhibiting the expression of the fibrosis-related factors IL-1ß, TNF-α, IL-4, and TGF-ß1. In conclusion, the PCL-DEX electrode coating shows promising application in CI surgery.

Preparation, characterization, and in vitro/vivo evaluation of dexamethasone/poly(ε-caprolactone)-based electrode coatings for cochlear implants.

With dexamethasone as the model drug and polycaprolactone (PCL) as the carrier material, a drug delivery coating for cochlear electrodes was prepared, to control cochlear fibrosis caused by cochlear implantation. A dexamethasone/poly (ε-caprolactone)-based electrode coating was prepared using the impregnation coating method. Preparation parameters were optimized, yielding 1 impregnation instance, impregnation time of 10 s, and PCL concentration of 10%. The coating was characterized in vitro using scanning electron microscopy, a universal machine, high-performance liquid chromatography, and CCK-8. The surface was porous and uniformly thick (average thickness, 48.67 µm)-with good flexibility, long-term slow drug release, and optimal drug concentration-and was biologically safe. The experimental results show that PCL is an ideal controlled-release material for dexamethasone as a drug carrier coating for cochlear implants.

Uniportal video-assisted thoracoscopic lung sparing tracheo-bronchial and carinal sleeve resections.

Pathology arising from the intrathoracic portion of the trachea (distal trachea), the carina and the main bronchi is usually neoplastic and is mainly treated with surgery. Resection of the intrathoracic portion of the trachea, the carina and the main bronchi for neoplastic lesions does not necessitate lung resection and is traditionally being conducted via open surgery. Video-assisted thoracic surgery (VATS) is witnessing an exponential growth and is the treatment of choice for early-stage non-small cell lung cancer (NSCLC). The experience accumulated over the past two decades along with the introduction of reliable and ergonomic technology, has led to the expansion of its indications. In this article we provide a detailed description of lung sparing distal tracheal, carinal and main bronchi resection for primary neoplasms of the airway, without involvement of the lung, with the uniportal video-assisted technique. The chest is entered through the fourth intercostal space, mid-axillary line. Dissection of the paratracheal space anteriorly, the tracheoesophageal groove posteriorly and the subcarinal space and division of the azygos arch are essential to mobilize the distal trachea and carina. Lateral dissection should be avoided beyond the points of division of the airway, as it may hinder the blood supply to the anastomosis. Any tension to the anastomosis should be relieved by release maneuvers. Ventilation is achieved through an endobronchial catheter, inserted into the left main bronchus through which a high-frequency jet ventilation catheter can be also inserted through it. The rationale of applying a minimally invasive technique for the conduction of tracheal and carinal resections, is to exploit its advantages, namely less pain, earlier mobilization and lower morbidity. Uniportal video-assisted resections of the distal trachea, carina and the main bronchi, are safe when conducted by experienced surgical and anesthetic teams.

CCNB2, NUSAP1 and TK1 are associated with the prognosis and progression of hepatocellular carcinoma, as revealed by co-expression analysis.

The mortality rate associated with hepatocellular carcinoma (HCC) is the third highest among all digestive system tumors. However, the causes of HCC development and the underlying mechanisms have remained to be fully elucidated. In the present bioinformatics study, genetic markers were identified and their association with HCC was determined. The mRNA expression datasets GSE87630, GSE74656 and GSE76427 were downloaded from the Gene Expression Omnibus (GEO) database. A total of 96 differentially expressed genes (DEGs) were screened from the 3 GEO datasets, including 25 upregulated and 71 downregulated genes. DEGs were uploaded to the database for Annotation, Visualization and Integrated Discovery to screen for enriched Gene Ontology terms in various categories and the Search Tool for the Retrieval of Interacting Genes/Proteins was used to identify the interactions and functions of the DEGs. A total of 3 genetic markers were identified in a stepwise pathway and functional analysis in a previous study. The association of the genetic markers with prognosis was analysed using the UALCAN online analysis tool. Regression analysis was also performed to identify the relationship between HCC grade and disease recurrence and the expression of genetic markers using The Cancer Genome Atlas HCC dataset. In addition, the expression of the 3 genetic markers in HCC tissues was determined using reverse transcription-quantitative PCR, the Oncomine database and the Human Protein Atlas database. The expression levels of the 3 genetic markers cyclin B2 (CCNB2), nucleolar and spindle-associated protein 1 (NUSAP1) and thymidine kinase 1 (TK1) were significantly correlated with each other and high mRNA expression of CCNB2 was significantly associated with poor overall survival of patients with HCC. Receiver operating characteristic curve analysis indicated that NUSAP1 and TK1 were capable of distinguishing between recurrent and non-recurrent HCC. Furthermore, CCNB2, NUSAP1 and TK1 were highly correlated with the HCC grade. It was also indicated that the mRNA expression of CCNB2, NUSAPA and TK1 was increased in primary HCC tissues when compared with that in adjacent tissues. The present study identified that the CCNB2, NUSAP1 and TK1 genes may serve as prognostic markers for HCC, and may be of value from the perspectives of basic research and clinical treatment of HCC.

Exogenous regucalcin negatively regulates the progression of cervical adenocarcinoma.

Cervical adenocarcinoma (CA) is a type of cervical cancer, and in previous decades its incidence has steadily increased. The upregulation of regucalcin (RGN) in various tumor cell types inhibits the progression of cancer. To understand the role of RGN in CA, RGN expression in human cervical cancer compared with normal tissues was analyzed using The Cancer Genome Atlas database (TCGA). Subsequently, transfection of lentivirus-mediated RGN into HeLa cells was conducted to study its function in tumor proliferation and metastasis. The expression of RGN and proteins associated with the Wnt/ß-catenin signaling pathway and epithelial-mesenchymal transition (EMT) were determined using reverse transcription-quantitative polymerase chain reaction and western blotting. Cell migration and invasion were evaluated using Transwell assays. Furthermore, cell proliferation, colony formation and cell cycle were assessed using the Cell Counting Kit-8, colony formation assay and flow cytometry, respectively. Lentivirus-mediated RGN effectively upregulated RGN expression, inhibited cell proliferation, retarded cellular invasion and promoted cell cycle arrest at the G2/M phase in HeLa cells. In addition, the expression levels of ß-catenin, p-glycogen synthase kinase (GSK)-3ß, matrix metalloproteinase (MMP)-3, MMP-7 and MMP-9 were effectively decreased, whilst those of E-cadherin and GSK-3ß were increased. The results suggest that RGN may be an inhibitory factor in tumorigenesis, and its mechanism of inhibiting tumor proliferation and metastasis may be associated with Wnt/ß-catenin signaling and EMT.

An Approach for Pulmonary Vascular Extraction from Chest CT Images.

Pulmonary vascular extraction from chest CT images plays an important role in the diagnosis of lung disease. To improve the accuracy rate of pulmonary vascular segmentation, a new pulmonary vascular extraction approach is proposed in this study. First, the lung tissue is extracted from chest CT images by region-growing and maximum between-class variance methods. Then the holes of the extracted region are filled by morphological operations to obtain complete lung region. Second, the points of the pulmonary vascular of the middle slice of the chest CT images are extracted as the original seed points. Finally, the seed points are spread throughout the lung region based on the fast marching method to extract the pulmonary vascular in the gradient image. Results of pulmonary vascular extraction from chest CT image datasets provided by the introduced approach are presented and discussed. Based on the ground truth pixels and the resulting quality measures, it can be concluded that the average accuracy of this approach is about 90%. Extensive experiments demonstrate that the proposed method has achieved the best performance in pulmonary vascular extraction compared with other two widely used methods.