Characteristics and evolution of karst collapse columns in the Huainan coalfield.

Karst collapse columns (KCCs) seriously affect the mining safety of deep coal seams. This study systematically summarizes and analyzes the development of KCCs, and classifies the different development stage to identify their development stages and evolutionary process in the Huainan coalfield. The evolution models for KCC development are given, combining with the exploration strata data from boreholes, the groundwater flow data of regional field, the hydrogeochemical data from the relative aquifers of KCC, and the hydrodynamic parameters. The results show that first types of KCCs are discovered in Liuzhuang and the Pansan mine, which is broken and disorganized, with a high degree of filling and cementation, and with the low permeability and velocity, and lower storage capacity. The KCCs in the Xieqiao and Zhangji mine have various morphologies and size differences. Their internal rocks are broken and semi-cemented, with a coefficient of permeability between 0.2 and 0.5 m/d and a specific discharge between 0.1 and 0.2 L/s•m. The KCCs are located in the cone of depression and are part of a sink area with moderate water-richness, where upper and lower aquifers have close hydraulic connections with mixed water quality. The internal core of the KCCs in the Gubei Mine is close to the center of the cone of depression which is highly broken and disorganized, with a high permeability, and a specific discharge more than 1.5 L/s•m. The intensity of runoff increases as its vertical depth also increases, especially the local areas are a higher hydraulic conductivity. Based on comprehensive hydrogeological characteristics, the KCCs development is divided into three stages: growing stage, declining stage, and dead stage. According to their characteristics of different stages, a series of evolutionary processes are established. Combining the sedimentological, karstological, and hydrogeological theories, some measures have been taken for prevention and control of mine water hazard in the various developmental stages. Hence, this research not only provides a new classified approach for KCC stages, but also an essential reference for a better understanding the mechanism of water inrush of KCCs in Northern China.

Construction of a non-negative matrix factorization model of immunogenic cell death-related genes in lung adenocarcinoma and analysis of survival prognosis.

Purpose: To explore the effectiveness of the model based on non-negative matrix factorization (NMF), analyze the tumor microenvironment and immune microenvironment for evaluating the prognosis of lung adenocarcinoma, establish a risk model, and screen independent prognostic factors. Methods: Downloading the transcription data files and clinical information files of lung adenocarcinoma from TCGA database and GO database, the R software was used to establish the NMF cluster model, and then the survival analysis between groups, tumor microenvironment analysis, and immune microenvironment analysis was performed according to the NMF cluster result. R software was used to construct prognostic models and calculate risk scores. Survival analysis was used to compare survival differences between different risk score groups. Results: Two ICD subgroups were established according to the NMF model. The survival of the ICD low-expression subgroup was better than that of the ICD high-expression subgroup. Univariate COX analysis screened out HSP90AA1, IL1, and NT5E as prognostic genes, and the prognostic model established on this basis has clinical guiding significance. Conclusion: The model based on NMF has the prognostic ability for lung adenocarcinoma, and the prognostic model of ICD-related genes has a certain guiding significance for survival.

A Privacy-Preserving Medical Data Sharing Scheme Based on Blockchain.

With the increasing penetration of the Internet of things (IoT) into people's lives, the limitations of traditional medical systems are emerging. First, the typical way of handling sensitive information can easily lead to privacy disclosure. Second, the medical system is relatively isolated. It is difficult for one medical system to share data with another, and the scope of users' activities is limited within the system boundary. To solve these two problems, we propose a new privacy-preserving medical data-sharing scheme by introducing the authorization mechanism and attribute-based encryption (ABE) based on blockchain, which breaks system boundaries and realizes data sharing among several medical institutions. ABE is used to realize scalable access control. In addition, doctors can share their knowledge to diagnose users by introducing many-to-many matching, which means that patients' health data can be represented by multiple keywords and doctors' expertise can be represented by multiple interests. We provide the correctness and security analysis of our scheme and implement a prototype tool on Ethereum. The experimental results show that our scheme solves the contradiction between the privacy preservation of medical data and the necessity of data sharing.

Characteristics of Fatty Acid Metabolism in Lung Adenocarcinoma to Guide Clinical Treatment.

Background: Lung adenocarcinoma (LUAD) has a very high morbidity and mortality rate, and its pathogenesis and treatment are still in the exploratory stage. Fatty acid metabolism plays a significant role in tumorigenesis, progression, and immune regulation. However, the gene expression of fatty acid metabolism in patients with LUAD and its relationship with prognosis remain unclear. Methods: We collected 309 fatty acid metabolism-related genes, established a LUAD risk model based on The Cancer Genome Atlas (TCGA) using Least Absolute Shrinkage Selection Operator (LASSO) regression analysis, and divided LUAD patients into high-risk and low-risk groups, which were further validated using the Gene Expression Omnibus (GEO) database. The nomogram, principal component analysis (PCA), and receiver operating characteristic (ROC) curves showed that the model had the best predictive performance. The ROC curves and calibration plots confirmed that the nomogram had good predictive power. We further analyzed the differences in clinical characteristics, immune cell infiltration, immune-related functions, chemotherapy drug sensitivity, and immunotherapy efficacy between the high-risk and low-risk groups. We also analyzed the enrichment pathways and protein-protein interaction (PPI) networks of different genes in the high-risk and low-risk groups to screen for target genes and further explored the correlation between target genes and differences in survival prognosis, clinical characteristics, gene mutations, and immune cells. Results: Risk score and staging are independent prognostic factors for patients with LUAD. The high-risk group had lower immune cell infiltration, was more sensitive to chemotherapeutic agents, and had a poorer survival prognosis. We also obtained three pivotal genes with poor survival prognosis in the high expression group, which were strongly associated with clinical symptoms and immune cells. Conclusion: Risk score and staging are independent prognostic factors for patients with LUAD. The high-risk group had lower immune cell infiltration, was more sensitive to chemotherapeutic agents, and had a poorer survival prognosis. We also obtained three survival prognosis-associated target genes that are closely associated with clinical symptoms and immune cells and may be potential targets for immune-targeted therapy in LUAD.

Metabolomic and Transcriptomic Profiling Identified Significant Genes in Thymic Epithelial Tumor.

Thymomas and thymic carcinomas are malignant thymic epithelial tumors (TETs) with poor outcomes if non-resectable. However, the tumorigenesis, especially the metabolic mechanisms involved, is poorly studied. Untargeted metabolomics analysis was utilized to screen for differential metabolic profiles between thymic cancerous tissues and adjunct noncancerous tissues. Combined with transcriptomic data, we comprehensively evaluated the metabolic patterns of TETs. Metabolic scores were constructed to quantify the metabolic patterns of individual tumors. Subsequent investigation of distinct clinical outcomes and the immune landscape associated with the metabolic scores was conducted. Two distinct metabolic patterns and differential metabolic scores were identified between TETs, which were enriched in a variety of biological pathways and correlated with clinical outcomes. In particular, a high metabolic score was highly associated with poorer survival outcomes and immunosuppressive status. More importantly, the expression of two prognostic genes (ASNS and BLVRA) identified from differential metabolism-related genes was significantly associated with patient survival and may play a key role in the tumorigenesis of TETs. Our findings suggest that differential metabolic patterns in TETs are relevant to tumorigenesis and clinical outcome. Specific transcriptomic alterations in differential metabolism-related genes may serve as predictive biomarkers of survival outcomes and potential targets for the treatment of patients with TETs.

ß-Caryophyllene from Chilli Pepper Inhibits the Proliferation of Non-Small Cell Lung Cancer Cells by Affecting miR-659-3p-Targeted Sphingosine Kinase 1 (SphK1).

BACKGROUND: ß-Caryophyllene is the main ingredient of chilli pepper and used for the prevention of various cancers, while the molecular mechanism for its effects on non-small cell lung cancer (NSCLC) remains unclear. METHODS: NSCLC cell lines A549 and NCI-H1299 were treated with ß-Caryophyllene and miR-659-3p (a potential tumor suppressor) mimic or siRNA. The levels of miR-659-3p, sphingosine kinase 1 (SphK1), apoptotic factors and oxidative stress factors were investigated. RESULTS: ß-Caryophyllene inhibited NSCLC growth, promoted their apoptotic rate, increased the level of miR-659-3p, apoptotic factors (cleaved caspase-3 and BAX), antioxidant factors (SOD, CAT and GPx) and reduced the level of oxidative stress (ROS and NO) and SphK1. miR-659-3p mimic and siRNA affected NSCLC growth, their apoptosis, and biochemical indices. CONCLUSION: ß-Caryophyllene of chilli pepper exerts inhibitory activity in NSCLC cells possibly by affecting miR-659-3p-targeted SphK1.

Microarray Identifies a Key Carcinogenic Circular RNA 0008594 That Is Related to Non-Small-Cell Lung Cancer Development and Lymph Node Metastasis and Promotes NSCLC Progression by Regulating the miR-760-Mediated PI3K/AKT and MEK/ERK Pathways.

PURPOSE: This study aimed to explore the circular RNA (circRNA/circ) profile engaged in non-small cell lung cancer (NSCLC) development and metastasis and to investigate potentially key carcinogenic circRNAs related to NSCLC. METHODS: CircRNA profiles between 10 NSCLC tissues and 10 adjacent tissues and between five NSCLC tissues with lymph node metastasis (LNM) and five NSCLC tissues without LNM were detected by Arraystar Human circRNA Array followed by bioinformatics. Circ_0008594 knockdown, circ_0004293 overexpression, and circ_0003832 overexpression plasmids were transfected into H23 and H460 cells to sort potential oncogenic circRNA. Then circ_0008594 overexpression and knockdown plasmids were transfected, followed by that circ_0008594 knockdown plus miR-760 knockdown plasmids were transfected into these cells. Cell proliferation, apoptosis, invasion, stemness, and pathways were detected. In addition, xenograft mice models were constructed via injecting H23 cells with circ_0008594 overexpression or knockdown to validate the findings. RESULTS: A total of 455 dysregulated circRNAs in NSCLC tissues versus adjacent tissues and 353 dysregulated circRNAs in NSCLC tissues with LNM versus those without LNM were discovered. Via cross-analysis, 19 accordant circRNAs were uncovered, among which three candidate circRNAs (circ_0008594, circ_0004293, circ_0003832) were chosen for functional experiments, during which it was observed that circ_0008549 affected H23 and H460 cell proliferation and apoptosis more obviously than circ_0004293 and circ_0003832. Subsequent experiments showed that circ_0008594 promoted H23 and H460 cell proliferation and invasion but affected stemness less and negatively regulated miR-760 via direct binding. Furthermore, miR-760 attenuated the effect of circ_0008549 on regulating H23 and H460 cell functions and the PI3K/AKT and MEK/ERK pathways. In vivo experiments further confirmed that circ_0008549 increased tumor volume, epithelial-mesenchymal transition, and the PI3K/AKT and MEK/ERK pathways while reducing tumor apoptosis and miR-760 NSCLC xenograft models. CONCLUSION: Our study identifies several valuable circRNAs related to NSCLC development and LNM. Furthermore, as a key functional circRNA, circ_0008594 was observed to promote NSCLC progression by regulating the miR-760-mediated PI3K/AKT and MEK/ERK pathways.

Formation environments and mechanisms of multistage paleokarst of Ordovician carbonates in Southern North China Basin.

With the reduction of oil and gas reserves and the increase of mining difficulty in Northern China, the carbonate rocks in Southern North China Basin are becoming a significant exploration target for carbonate reservoirs. However, the development characteristics, formation stages, formation environments and mechanisms of the carbonate reservoirs in Southern North China Basin are still unclear, which caused the failures of many oil and gas exploration wells. This study focused on addressing this unsolved issue from the Ordovician carbonate paleokarst in the Huai-Fu Basin, which is located in the southeast of Southern North China Basin and one of the key areas for oil and gas exploration. Based on petrology, mineralogy and geochemical data, pore types, distribution characteristics, and formation stages of the Ordovician paleokarst were analyzed. Then, in attempt to define the origins of porosity development, the formation environments and mechanisms were illustrated. The results of this study showed that pore types of the Ordovician carbonates in the Huai-Fu Basin are mainly composed of intragranular pores, intercrystalline (intergranular) pores, dissolution pores (vugs), fractures, channels, and caves, which are usually in fault and fold zones and paleoweathering crust. Furthermore, five stages and five formation environments of the Ordovician paleokarst were identified. Syngenetic karst, eogenetic karst, and paleoweathering crust karst were all developed in a relatively open near-surface environment, and their formations are mainly related to meteoric water dissolution. Mesogenetic karst was developed in a closed buried environment, and its formation is mainly related to the diagenesis of organic matters and thermochemical sulfate reduction in the Permian-Carboniferous strata. Hydrothermal (water) karst was developed in a deep-buried and high-temperature environment, where hydrothermal fluids (waters) migrated upward through structures such as faults and fractures to dissolve carbonate rocks and simultaneously deposited hydrothermal minerals and calcites. Lastly, a paleokarst evolution model, combined with the related porosity evolution processes, nicely revealed the Ordovician carbonate reservoir development. This study provides insights and guidance for further oil and gas exploration in the Southern North China Basin, and also advances our understanding of the genesis of carbonate paleokarst around the world.

Therapeutic Potential of Glutamine Pathway in Lung Cancer.

Cancer cells tend to obtain the substances needed for their development depending on altering metabolic characteristics. Among the reorganized metabolic pathways, Glutamine pathway, reprogrammed to be involved in the physiological process including energy supply, biosynthesis and redox homeostasis, occupies an irreplaceable role in tumor cells and has become a hot topic in recent years. Lung cancer currently maintains a high morbidity and mortality rate among all types of tumors and has been a health challenge that researchers have longed to overcome. Therefore, this study aimed to clarify the essential role of glutamine pathway played in the metabolism of lung cancer and its potential therapeutic value in the interventions of lung cancer.

Generalized Centered 2-D Principal Component Analysis.

Most existing robust principal component analysis (PCA) and 2-D PCA (2DPCA) methods involving the l2 -norm can mitigate the sensitivity to outliers in the domains of image analysis and pattern recognition. However, existing approaches neither preserve the structural information of data in the optimization objective nor have the robustness of generalized performance. To address the above problems, we propose two novel center-weight-based models, namely, centered PCA (C-PCA) and generalized centered 2DPCA with l2,p -norm minimization (GC-2DPCA), which are developed for vector- and matrix-based data, respectively. The C-PCA can preserve the structural information of data by measuring the similarity between the data points and can also retain the PCA's original desirable properties such as the rotational invariance. Furthermore, GC-2DPCA can learn efficient and robust projection matrices to suppress outliers by utilizing the variations between each row of the image matrix and employing power p of l2,1 -norm. We also propose an efficient algorithm to solve the C-PCA model and an iterative optimization algorithm to solve the GC-2DPCA model, and we theoretically analyze their convergence properties. Experiments on three public databases show that our models yield significant improvements over the state-of-the-art PCA and 2DPCA approaches.

Prevalence and correlation of anxiety and depression on the prognosis of postoperative non-small-cell lung cancer patients in North China.

Identify the prevalence of postoperative anxiety and depression as well as their correlations with clinical features and survival profiles in non-small-cell lung cancer (NSCLC) patients who underwent resection.Four hundred NSCLC patients who underwent resection were recruited, and their anxiety and depression were assessed by hospital anxiety and depression scale (HADS) at discharge after surgery. Besides, 480 healthy controls (HCs) were also enrolled and assessed by HADS.The HADS-Anxiety score of NSCLC patients (7.8 ±â€Š3.9) was greatly higher than that of HCs (4.8 ±â€Š2.7), and the anxiety prevalence of NSCLC patients (49.6%) were dramatically increased compared with HCs (13.8%). Furthermore, the HADS-Depression score (7.2 ±â€Š3.6) of NSCLC patients was considerably increased compared with HCs (4.2 ±â€Š2.6), and the depression prevalence of NSCLC patients (38.3%) was significantly raised compared with HCs (10.0%). Besides, anxiety correlated with gender, marital status, hypertension, diabetes, pathological differentiation, tumor size, lymph node metastasis, TNM stage and carcinoembryonic antigen level, meanwhile, depression correlated with marital status, employment status before surgery, diabetes, pathological differentiation, and TNM stage in NSCLC patients. Additionally, the anxiety and depression predicted shorter disease-free survival in NSCLC patients. And the anxiety predicted worse overall survival (OS), while no association of depression with OS was observed in NSCLC patients.Post-operative anxiety and depression are highly prevalent and implicated in the ongoing care and prognosis prediction in NSCLC patients who underwent resection.

The effects of ß-TCP on mechanical properties, corrosion behavior and biocompatibility of ß-TCP/Zn-Mg composites.

Zinc has attracted increasing attention in the field of degradable implant materials due to its suitable degradation rate. To further improve the mechanical properties and biocompatibility of zinc, Zn-1Mg-nvol%ß-TCP (n = 0, 1, 3, 5) composites were fabricated for biomedical application by the mechanical stirring combined with ultrasonic assisted casting and hot extrusion technology. The microstructure, mechanical properties and corrosion behavior of these composites were systemically investigated and the composite with the best comprehensive performance were selected for biocompatibility evaluation including L-929 cells cytotoxicity test and SD rat model experiment. Tensile test revealed that Zn-1Mg-1vol%ß-TCP composite possessed optimal mechanical properties. The yield strength (YS), ultimate tensile strength (UTS), elongation (σ) and elastic modulus (E) of the as-extruded Zn-1Mg-1vol%ß-TCP composite are 250.8 MPa, 330.5 MPa, 11.7% and 125.4 GPa respectively. The immersion tests showed that the corrosion resistance of the composite is slightly decreased with the increase of ß-TCP content. In addition, the addition of ß-TCP makes the cytocompatibility of the composites better than that of the Zn-1Mg alloy matrix. Various blood biochemical parameters in rat serum samples after implantation showed Zn-1Mg alloy and Zn-1Mg-ß-TCP composites has not significant tissue inflammation and showed good biocompatibility.

Transcription Factor p53 Suppresses Tumor Growth by Prompting Pyroptosis in Non-Small-Cell Lung Cancer.

OBJECTIVE: To evaluate the effect of p53 on pyroptosis and its inhibitory role on tumor growth in non-small-cell lung cancer (NSCLC). METHODS: The correlation of p53 and pyroptosis was determined in tumor tissues of NSCLC patients. The pyroptotic level was detected in A549 cells to clarify the effect of p53 on pyroptosis. p53 overexpression A549 tumor-bearing mice were used to clarify the therapeutic target of p53 in NSCLC treatment. RESULTS: p53 expression level was positively related to pyroptosis in NSCLC tissues. In in vitro assays, p53 directly regulated pyroptosis in A549 cells. p53-specific knockdown blocked lipopolysaccharide- (LPS-) induced pyroptosis. In in vivo assays, p53 overexpression in A549 markedly decreased tumor growth and death rate by increasing the pyroptotic level. CONCLUSIONS: Upregulation of p53 prompts pyroptosis to produce anti-NSCLC effects suggesting the potential of p53 on suppressing tumor growth in NSCLC patients.

Fabrication of biodegradable HA/Mg-Zn-Ca composites and the impact of heterogeneous microstructure on mechanical properties, in vitro degradation and cytocompatibility.

Due to their desirable elastic modulus and density that are similar to natural bone, non-toxic element containing magnesium alloys are regarded as promising bio-degradable materials. A biodegradable HA-particle-reinforced magnesium-matrix composite Mg-3Zn-0.2Ca-1HA (wt%) was fabricated for biomedical application by a combination of high shear solidification (HSS) and hot extrusion technology. The microstructure, mechanical properties, corrosion resistance and cell biocompatibility of the composite were subsequently investigated. In comparison with the matrix alloy, the as-cast Mg-3Zn-0.2Ca-1HA composite obtained by HSS technology exhibited a uniform and fine grained structure, further refined after a hot extrusion ratio of 36:1. The yield strength (0.2%YS), ultimate tensile strength and elongation of the extruded composite were 322 MPa, 341 MPa and 7.6%, respectively. The corrosion rate of the as-extruded Mg-3Zn-0.2Ca-1HA composite was measured to be 1.52 mm/y. Electrochemical and immersion tests showed that the corrosion resistance of the composite is slightly improved comparing to that of the matrix alloy.

Circular RNA hsa_circ_0008305 (circPTK2) inhibits TGF-ß-induced epithelial-mesenchymal transition and metastasis by controlling TIF1γ in non-small cell lung cancer.

BACKGROUND: TGF-ß promotes tumor invasion and metastasis through inducing epithelial-mesenchymal transition (EMT) in non-small cell lung cancer (NSCLC). Circular RNAs (circRNAs) are recognized as functional non-coding RNAs involved in human cancers. However, whether and how circRNAs contribute to TGF-ß-induced EMT and metastasis in NSCLC remain vague. Here, we investigated the regulation and function of Circular RNA hsa_circ_0008305 (circPTK2) in TGF-ß-induced EMT and tumor metastasis, as well as a link between circPTK2 and transcriptional intermediary factor 1 γ (TIF1γ) in NSCLC. METHODS: Circular RNAs were determined by human circRNA Array analysis, real-time quantitative reverse transcriptase PCR and northern blot. Luciferase reporter, RNA-binding protein immunoprecipitation (RIP), RNA pull-down and fluorescence in situ hybridization (FISH) assays were employed to test the interaction between circPTK2 and miR-429/miR-200b-3p. Ectopic overexpression and siRNA-mediated knockdown of circPTK2, TGF-ß-induced EMT, Transwell migration and invasion in vitro, and in vivo experiment of metastasis were used to evaluate the function of circPTK2. Transcription and prognosis analyses were done in public databases. RESULTS: CircPTK2 and TIF1γ were significantly down-regulated in NSCLC cells undergoing EMT induced by TGF-ß. CircPTK2 overexpression augmented TIF1γ expression, inhibited TGF-ß-induced EMT and NSCLC cell invasion, whereas circPTK2 knockdown had the opposite effects. CircPTK2 functions as a sponge of miR-429/miR-200b-3p, and miR-429/miR-200b-3p promote TGF-ß-induced EMT and NSCLC cell invasion by targeting TIF1γ. CircPTK2 overexpression inhibited the invasion-promoting phenotype of endogenous miR-429/miR-200b-3p in NSCLC cells in response to TGF-ß. CircPTK2 overexpression significantly decreased the expression of Snail, an important downstream transcriptional activator of TGF-ß/Smad signaling. In an in vivo experiment of metastasis, circPTK2 overexpression suppressed NSCLC cell metastasis. Moreover, circPTK2 expression was dramatically down-regulated and positively correlated with TIF1γ expression in human NSCLC tissues. Especially, circPTK2 was significantly lower in metastatic NSCLC tissues than non-metastatic counterparts. CONCLUSION: Our findings show that circPTK2 (hsa_circ_0008305) inhibits TGF-ß-induced EMT and metastasis by controlling TIF1γ in NSCLC, revealing a novel mechanism by which circRNA regulates TGF-ß-induced EMT and tumor metastasis, and suggesting that circPTK2 overexpression could provide a therapeutic strategy for advanced NSCLC.

Long non-coding RNA XIST promotes TGF-ß-induced epithelial-mesenchymal transition by regulating miR-367/141-ZEB2 axis in non-small-cell lung cancer.

Growing evidence shows that lncRNA XIST functions as an oncogene accelerating tumor progression. Transforming growth factor ß (TGF-ß)-induced epithelial-mesenchymal transition (EMT) plays a key role in tumor metastasis. However, it is still unclear whether lncRNA XIST is implicated in TGF-ß-induced EMT and influences cell invasion and metastasis in non-small-cell lung cancer (NSCLC). Here, we observed increased expression of lncRNA XIST and ZEB2 mRNA in metastatic NSCLC tissues. Knockdown of lncRNA XIST inhibited ZEB2 expression, and repressed TGF-ß-induced EMT and NSCLC cell migration and invasion. Being in consistent with the in vitro findings, the in vivo experiment of metastasis showed that knockdown of lncRNA XIST inhibited pulmonary metastasis of NSCLC cells in mice. In addition, knockdown of ZEB2 expression can inhibit TGF-ß-induced EMT and NSCLC cell migration and invasion. Mechanistically, lncRNA XIST and ZEB2 were targets of miR-367 and miR-141. Furthermore, both miR-367 and miR-141 expression can be upregulated by knockdown of lncRNA XIST. Taken together, our study reveals that lncRNA XIST can promote TGF-ß-induced EMT and cell invasion and metastasis by regulating miR-367/miR-141-ZEB2 axis in NSCLC.

Cordycepin inhibits LPS-induced acute lung injury by inhibiting inflammation and oxidative stress.

Acute lung injury (ALI) is a common severe clinical syndrome in intensive care unit. Inflammation has been reported to play a critical role in the development of ALI. Cordycepin, an active component isolated from Cordyceps militaris, has been reported to have anti-inflammatory effects. However, the anti-inflammatory effects of cordycepin on LPS-induced ALI remain unclear. Therefore, in the present study, we assessed whether cordycepin could attenuate ALI induced by LPS. The mice were conditioned with cordycepin 1h before intranasal instillation of LPS. Lung wet/dry (W/D) ratio, MPO activity, MDA content, and inflammatory cytokines production were detected. The expression of NF-κB p65, I-κB, Nrf2, and HO-1 were detected by western blot analysis. We found that LPS significantly increased lung wet/dry (W/D) ratio, MPO activity, MDA content, and inflammatory cytokines production. However, the increases were significantly inhibited by treatment of cordycepin. LPS-induced NF-κB activation was also suppressed by cordycepin. In addition, cordycepin was found to up-regulate the expression of Nrf2 and HO-1 in a dose-dependent manner. In conclusion, our results demonstrated that cordycepin could attenuate LPS-induced ALI effectively, probably due to inhibition of inflammation and oxidative stress.

Artesunate Protects LPS-Induced Acute Lung Injury by Inhibiting TLR4 Expression and Inducing Nrf2 Activation.

Artesunate, a derivative of artemisinin, has been reported to have anti-inflammatory property. However, few studies showed the protective effects of artesunate on lung injury. In this study, we aimed to investigate the effects of artesunate on LPS-induced lung injury in mice. The mice were treated with artesunate 1 h before or after LPS treatment. The effects of artesunate on lung MPO activity and malondialdehyde (MDA) content were detected. The lung wet/dry radio and the numbers of inflammatory cells in BALF were also measured. ELISA was used to evaluate the levels of TNF-α, IL-1ß, and IL-6 in BALF. Western blot analysis was adapted to detect TLR4 and Nrf2 signaling pathways. The results showed that artesunate protected against LPS-induced ALI by decreasing the numbers of inflammatory cells, lung edema, MPO activity, and MDA content. Furthermore, artesunate significantly inhibited the levels of TNF-α, IL-1ß, and IL-6. Artesunate also inhibited LPS-induced IL-6 and IL-8 production in the A549 cells. In addition, artesunate dose-dependently suppressed LPS-induced TLR4 expression and NF-κB activation. The expression of Nrf2 and HO-1 were also up-regulated by artesunate. The data suggest that artesunate possesses anti-inflammatory and anti-oxidant properties against LPS-induced ALI via inhibiting TLR4 signaling pathway and activating Nrf2 signaling pathway.

Prognostic significance of sphingosine kinase 2 expression in non-small cell lung cancer.

Sphingosine kinase 2 (SphK2) as a conserved lipid kinase has not been thoroughly elucidated in non-small cell lung cancer (NSCLC). The aim of the present study was to evaluate the expression of SphK2 in NSCLC tissues and to determine its correlation with clinicopathologic characteristics and its impact on patient prognosis. We assessed the expression of SphK2 and proliferating cell nuclear antigen (PCNA) (as a proliferative index) by immunohistochemistry in 180 NSCLC patient's formalin-fixed paraffin-embedded tissue blocks. Relationship between the expression of SphK2 and PCNA and various clinicopathological features in these patients was evaluated. We detected that expression of SphK2 was gradually upregulated from normal, metaplasia/dysplasia tissues to NSCLC tissues. At the same time, PCNA expression followed a similar pattern. Statistical analysis showed that expression of SphK2 in NSCLC tissues was strongly associated with PCNA expression, histology grade, live vaccine strain invasion, lymph node status, clinical stage, tumors size, and histology type. Patients with SphK2 overexpression in their tissues had lower overall survival (OS) and disease-free survival (DFS) rates than those with low SphK2 expression. Using uni- and multivariate analysis, we found that SphK2 overexpression was an independent prognostic factor for both OS and DFS. The expression of SphK2 parallels the progression of NSCLC, and SphK2 overexpression may represent a novel and potentially independent biomarker for the prognosis of patients with NSCLC.