Vanadate Bio-Detoxification Driven by Pyrrhotite with Secondary Mineral Formation.

Vanadium(V) is a redox-sensitive heavy-metal contaminant whose environmental mobility is strongly influenced by pyrrhotite, a widely distributed iron sulfide mineral. However, relatively little is known about microbially mediated vanadate [V(V)] reduction characteristics driven by pyrrhotite and concomitant mineral dynamics in this process. This study demonstrated efficient V(V) bioreduction during 210 d of operation, with a lifespan about 10 times longer than abiotic control, especially in a stable period when the V(V) removal efficiency reached 44.1 ± 13.8%. Pyrrhotite oxidation coupled to V(V) reduction could be achieved by an enriched single autotroph (e.g., Thiobacillus and Thermomonas) independently. Autotrophs (e.g., Sulfurifustis) gained energy from pyrrhotite oxidation to synthesize organic intermediates, which were utilized by the heterotrophic V(V) reducing bacteria such as Anaerolinea, Bacillus, and Pseudomonas to sustain V(V) reduction. V(V) was reduced to insoluble tetravalent V, while pyrrhotite oxidation mainly produced Fe(III) and SO42-. Secondary minerals including mackinawite (FeS) and greigite (Fe3S4) were produced synchronously, resulting from further transformations of Fe(III) and SO42- by sulfate reducing bacteria (e.g., Desulfatiglans) and magnetotactic bacteria (e.g., Nitrospira). This study provides new insights into the biogeochemical behavior of V under pyrrhotite effects and reveals the previously overlooked mineralogical dynamics in V(V) reduction bioprocesses driven by Fe(II)-bearing minerals.

Vanadium in the Environment: Biogeochemistry and Bioremediation.

Vanadium(V) is a highly toxic multivalent, redox-sensitive element. It is widely distributed in the environment and employed in various industrial applications. Interactions between V and (micro)organisms have recently garnered considerable attention. This Review discusses the biogeochemical cycling of V and its corresponding bioremediation strategies. Anthropogenic activities have resulted in elevated environmental V concentrations compared to natural emissions. The global distributions of V in the atmosphere, soils, water bodies, and sediments are outlined here, with notable prevalence in Europe. Soluble V(V) predominantly exists in the environment and exhibits high mobility and chemical reactivity. The transport of V within environmental media and across food chains is also discussed. Microbially mediated V transformation is evaluated to shed light on the primary mechanisms underlying microbial V(V) reduction, namely electron transfer and enzymatic catalysis. Additionally, this Review highlights bioremediation strategies by exploring their geochemical influences and technical implementation methods. The identified knowledge gaps include the particulate speciation of V and its associated environmental behaviors as well as the biogeochemical processes of V in marine environments. Finally, challenges for future research are reported, including the screening of V hyperaccumulators and V(V)-reducing microbes and field tests for bioremediation approaches.

Prognostic factors in patients with thymoma who underwent surgery.

PURPOSE: Thymoma is the most common primary tumor in the anterior mediastinum. The prognostic factors of patients with thymoma still need to be clarified. In this study, we aimed to investigate the prognostic factors of patients with thymoma who received radical resection and establish the nomogram to predict the prognosis of these patients. MATERIALS AND METHODS: Patients who underwent radical resection for thymoma with complete follow-up data between 2005 and 2021 were enrolled. Their clinicopathological characteristics and treatment methods were retrospectively analyzed. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method and compared by the log-rank test. Univariate and multivariate Cox proportional hazards regression analyses were performed to identify the independent prognostic factors. According to the results of the univariate analysis in the Cox regression model, the predictive nomograms were created. RESULTS: A total of 137 patients with thymoma were enrolled. With a median follow-up of 52 months, the 5-year and 10-year PFS rates were 79.5% and 68.1%, respectively. The 5-year and 10-year OS rates were 88.4% and 73.1%, respectively. Smoking status (P = 0.022) and tumor size (P = 0.039) were identified as independent prognostic factors for PFS. Multivariate analysis showed that a high level of neutrophils (P = 0.040) was independently associated with OS. The nomogram showed that the World Health Organization (WHO) histological classification contributed more to the risk of recurrence than other factors. Neutrophil count was the most important predictor of OS in patients with thymoma. CONCLUSION: Smoking status and tumor size are risk factors for PFS in patients with thymoma. A high level of neutrophils is an independent prognostic factor for OS. The nomograms developed in this study accurately predict PFS and OS rates at 5 and 10 years in patients with thymoma based on individual characteristics.

Clinical characteristics and patient outcomes of molecular subtypes of small cell lung cancer (SCLC).

BACKGROUND: Recent studies have shown that according to the expression levels of achaete-scute homolog 1 (ASCL1), neurogenic differentiation factor 1 (NEUROD1), and POU class 2 homeobox 3 (POU2F3), small cell lung cancer (SCLC) can be divided into four subtypes: SCLC-A (ASCL1-dominant), SCLC-N (NEUROD1-dominant), SCLC-P (POU2F3-dominant), and SCLC-I (triple negative or SCLC-inflamed). However, there are limited data on the clinical characteristics and prognosis of molecular subtypes of SCLC. METHODS: Immunohistochemistry (IHC) was used to detect the expression levels of ASCL1, NEUROD1, and POU2F3 in 53 patient samples of resectable SCLC. The subtype was defined by the differential expression of the transcription factors for ASCL1, NEUROD1, and POU2F3 or the low expression of all three factors with an inflamed gene signature (SCLC-A, SCLC-N, SCLC-P, and SCLC-I, respectively). The clinicopathological characteristics, immunological features (programmed death ligand 1 [PD-L1] expression and CD8+ tumor infiltrating lymphocyte [TIL] density), and patient outcomes of the four subtypes of SCLC were analyzed. RESULTS: Positive ASCL1, NEUROD1, and POU2F3 staining was detected in 43 (79.2%), 27 (51.0%), and 17 (32.1%) SCLC specimens by IHC. According to the results of IHC analysis, SCLC was divided into four subtypes: SCLC-A (39.6%), SCLC-N (28.3%), SCLC-P (17.0%), and SCLC-I (15.1%). The 5-year overall survival (OS) rates of these four subtypes were 61.9%, 69.3%, 41.7%, and 85.7%, respectively (P=0.251). There were significant differences in smoking status among different subtypes of SCLC (P= 0.031). However, we did not confirm the correlation between subtypes of SCLC and other clinicopathological factors or immune profiles. Cox multivariate analysis showed that N stage (P=0.025), CD8+ TILs (P=0.024), Ki-67 level (P=0.040), and SCLC-P (P=0.023) were independent prognostic factors for resectable SCLC. CONCLUSIONS: Our IHC-based study validated the proposed classification of SCLC using the expression patterns of key transcriptional regulatory factors. We found that SCLC-P was associated with smokers and was one of the poor prognostic factors of limited-stage SCLC. In addition, no correlation was found between PD-L1 expression or CD8+ TIL density and SCLC subtypes.

Influence of tillage practices on phosphorus forms in aggregates of Mollisols from northeast China.

BACKGROUND: Phosphorus (P) is an essential mineral nutrient for crop growth and development. Much remains unknown regarding the content and distribution of P forms in different soil aggregates as affected by tillage practices. A 3-year field experiment was conducted to investigate the effects of no-tillage (NT), rotary tillage (RT), subsoiling (SS), and deep tillage (DT) on soil aggregate distribution pattern, aggregate-associated P content, and to understand the conversion trend. RESULTS: Tillage has the potential to accelerate the processes in transforming macro-aggregates (> 0.25 mm) into micro-aggregates (< 0.25 mm). Greatest aggregate stability was attained under RT. Total phosphorus (TP) and available phosphorus (AP) under NT were increased by 21.1-82.0% in contrast to other tillage treatments. The NT had high content in inorganic phosphorus (IP), aluminum phosphorus (Al-P), and iron phosphorus (Fe-P) with 416.7, 107.9, and 99.1 mg·kg-1 on average, respectively. Aggregates with a size dimension of < 2 mm were more sensitive than other sizes of aggregates. IP was evenly distributed throughout all aggregates, ranging from 336.3 to 430.6 mg kg-1 . No differences in organic phosphorus (OP) were found in all tillage treatments, while NT promoted the transformation of labile OP to IP. The AP and OP were generally more abundant in aggregates of 2 to 0.25 mm and < 0.25 mm. CONCLUSION: Short-term NT can improve soil structure and increase P reserves, thus, enhancing the conversion of P from being scarce to available. © 2021 Society of Chemical Industry.

NOX4 expression and distal arteriolar remodeling correlate with pulmonary hypertension in COPD.

BACKGROUND: Pulmonary hypertension (PH) in chronic obstructive pulmonary disease (COPD) is suggested as the consequence of emphysematous destruction of vascular bed and hypoxia of pulmonary microenvironment, mechanisms underpinning its pathogenesis however remain elusive. The dysregulated expression of nicotinamide adenine dinucleotide phosphate (NADPH)-oxidases and superoxide generation by pulmonary vasculatures have significant implications in the hypoxia-induced PH. METHODS: In this study, the involvement of NADPH oxidase subunit 4 (NOX4) in pulmonary arteriolar remodeling of PH in COPD was investigated by ascertaining the morphological alteration of pulmonary arteries and pulmonary blood flow using cardiac magnetic resonance imaging (cMRI), and the expression and correlation of NOX4 with pulmonary vascular remodeling and pulmonary functions in COPD lungs. RESULTS: Results demonstrated that an augmented expression of NOX4 was correlated with the increased volume of pulmonary vascular wall in COPD lung. While the volume of distal pulmonary arteries was inversely correlated with pulmonary functions, despite it was positively associated with the main pulmonary artery distensibility, right ventricular myocardial mass end-systolic and right ventricular myocardial mass end-diastolic in COPD. In addition, an increased malondialdehyde and a decreased superoxide dismutase were observed in sera of COPD patients. Mechanistically, the abundance of NOX4 and production of reactive oxygen species (ROS) in pulmonary artery smooth muscle cells could be dynamically induced by transforming growth factor-beta (TGF-ß), which in turn led pulmonary arteriolar remodeling in COPD lungs. CONCLUSION: These results suggest that the NOX4-derived ROS production may play a key role in the development of PH in COPD by promoting distal pulmonary vascular remodeling.

Deciphering Vanadium Speciation in Smelting Ash and Adaptive Responses of Soil Microorganisms.

Abundant smelting ash is discharged during pyrometallurgical vanadium (V) production. However, its associated V speciation and resultant ecological impact have remained elusive. In this study, V speciation in smelting ash and its influence on the metabolism of soil microorganisms were investigated. Smelting ashes from V smelters contained abundant V (19.6-115.9 mg/g). V(V) was the dominant species for soluble V, while solid V primarily existed in bioavailable forms. Previously unrevealed V nanoparticles (V-NPs) were prevalently detected, with a peak concentration of 1.3 × 1013 particles/g, a minimal size of 136.0 ± 0.6 nm, and primary constituents comprising FeVO4, VO2, and V2O5. Incubation experiments implied that smelting ash reshaped the soil microbial community. Metagenomic binning, gene transcription, and component quantification revealed that Microbacterium sp. and Tabrizicola sp. secreted extracellular polymeric substances through epsB and yhxB gene regulation for V-NPs aggregation to alleviate toxicity under aerobic operations. The V K-edge X-ray absorption near-edge structure (XANES) spectra suggested that VO2 NPs were oxidized to V2O5 NPs. In the anaerobic case, Comamonas sp. and Achromobacter sp. reduced V(V) to V(IV) for detoxification regulated by the napA gene. This study provides a deep understanding of the V speciation in smelting ash and microbial responses, inspiring promising bioremediation strategies to reduce its negative environmental impacts.

TRIM13 inhibits cell proliferation and induces autophagy in lung adenocarcinoma by regulating KEAP1/NRF2 pathway.

Lung adenocarcinoma (LUAD) is the most common type of lung cancer. Tripartite motif 13 (TRIM13) is a member of TRIM protein family and is downregulated in multiple cancers, especially non-small cell lung cancers (NSCLC). In this study, we investigated anti-tumor mechanism of TRIM13 in non-small cell lung cancer tissues and cell lines. First, the mRNA and protein levels of TRIM13 in LUAD tissue and cells were measured. TRIM13 was overexpressed on LUAD cells to investigate the effects on cell proliferation, apoptosis, oxidative stress, p62 ubiquitination, and autophagy activation. Finally, mechanistic role of TRIM13 in regulating the Keap1/Nrf2 pathway was investigated. Results indicated that low level of TRIM13 mRNA and protein expression was found in LUAD tissue and cells. Overexpression of TRIM13 in LUAD cancer cells suppressed their proliferation, increased apoptosis, and oxidative stress, ubiquitinated p62, and activated autophagy via the RING finger domain of TRIM13. Furthermore, TRIM13 showed interaction with p62 and mediated its ubiquitination and degradation in LUAD cells. Mechanistically, TRIM13 exerted the tumor suppressor functions in LUAD cells by negatively regulating Nrf2 signaling and downstream antioxidants, which was further confirmed by in vivo data from xenografts. In conclusion, TRIM13 behaves like a tumor suppressor and triggers autophagy in LUAD cells by mediating p62 ubiquitination via KEAP1/Nrf2 pathway. Our findings provide a novel insight into targeted therapy plans for LUAD.

Algal or bacterial community: Who can be an effective indicator of the impact of reclaimed water recharge in an urban river.

Reclaimed water has been widely utilized for water resource replenishment, yet little is known regarding its impacts on various microorganisms in the receiving water. To address this knowledge gap, we systematically investigated the responses of bacteria and algae to the recharge of reclaimed water by using the high-throughput sequencing technology in the urban Chaobai River. After the inputs of reclaimed water, lower contents of NO2--N, NH4+-N, and TP were observed in the downstream section compared to that of upstream without reclaimed water, indicating that reclaimed water could improve the water quality of the receiving water. Correspondingly, both bacterial and algal communities showed the decreased network complexity in the downstream section, but many common freshwater bacteria and typical bloom-forming algae were dominant in the downstream, potentially suggesting that algae were more sensitive to the local environmental conditions. More importantly, although nitrogen and phosphorus served as the paramount factors in shaping both bacterial and algal communities, environmental selection contributed more to algal rather than bacterial community, and simultaneously algal variations could further affect bacterial dynamics in the urban river. Overall, these findings revealed distinct characteristics of bacteria and algae in responding to the reclaimed water recharge, highlighting the superiority of algae in indicating environmental changes, especially in monitoring and regulating the replenishment of reclaimed water in urban rivers.

Hypoxic Microenvironment-Induced Reduction in PTEN-L Secretion Promotes Non-Small Cell Lung Cancer Metastasis through PI3K/AKT Pathway.

Objective: Lung cancer is the leading cause of cancer-related deaths worldwide. The aim of this study was to investigate the effects of hypoxic microenvironment on PTEN-L secretion and the effects of PTEN-L on the metastasis of non-small cell lung cancer (NSCLC) and the potential mechanisms. Methods: The expression levels of PTEN-L in NSCLC tissues, cells, and cell culture media were detected. The transfection of PTEN-L overexpression construct or HIF-1α-siRNAs was conducted to manipulate the expression of PTEN-L or HIF-1α. NSCLC cells were introduced into 200 µM CoCl2 medium for 72 hours under 37°C to simulate hypoxia. The proliferation and apoptosis of the A549 cells were determined by the Cell Counting Kit-8 assay and Annexin V-FITC/PI-stained flow cytometry assay, respectively. Wound healing assay and transwell invasion assay were used to measure the migration and invasion of A549 cells. The protein expression of PTEN, PTEN-L, PI3K/AKT pathway-related proteins, and HIF-1α was detected by Western blot. Results: PTEN and PTEN-L are downregulated in lung cancer tissues and cells. The protein expression of PTEN-L in the culture medium of lung cancer cell lines is decreased. The hypoxic microenvironment inhibits PTEN-L secretion. The low level of PTEN-L promotes cell proliferation, migration, and invasion, as well as inhibits apoptosis of A549 cells. The overexpression of PTEN-L attenuated the activation of the PI3K/AKT pathway by the hypoxic microenvironment. The knockdown of HIF-1α upregulates PTEN-L secretion under hypoxia. Conclusions: The hypoxic microenvironment inhibits PTEN-L secretion and thus activates PI3K/AKT pathway to induce proliferation, migration, and invasion promotion, and apoptosis inhibition in NSCLC cells.

Clinical Significance of Expression of Periostin in Non-small Cell Lung Cancer.

OBJECTIVE: To analyse the expression of serum periostin in patients with non-small cell lung cancer (NSCLC) and its clinical significance. STUDY DESIGN: Descriptive study. PLACE AND DURATION OF STUDY: General Hospital of Ningxia Medical University, Yinchuan, China, from October 2018 to October 2019. METHODOLOGY: Patients with NSCLC, benign lung lesions, and healthy volunteers (controls) were enrolled. Serum periostin level of all the patients with NSCLC was determined by the enzyme-linked immunosorbent assayed upon admission. The receiver operating characteristic (ROC) curve was used to evaluate the value of serum periostin predicting metastasis and recurrence. RESULTS: The serum periostin level in the NSCLC group (n=66) was significantly higher than that of the benign group (n=40), control group (n= 38, p<0.001), and in patients with different T and N stages in the NSCLC group (p<0.001). The serum levels of periostin in patients with metastasis and recurrence within one year were significantly higher than those without that (p<0.001). When the serum periostin level was 54.12 ng/mL, the area under the curve (AUC) predicting postoperative recurrence of NSCLC in patients was 0.739, with 69.23% sensitivity and 75.47% specificity. When the serum periostin level was 42.84 ng/mL, the AUC predicting postoperative metastasis of NSCLC in patients was 0.831, with 80.00% sensitivity and 82.93% specificity. CONCLUSION: Serum periostin level is possibly related to the progression of NSCLC and exhibited certain predictive values for the prognosis of NSCLC patients. The value of periostin level predicting metastasis was greater than predicting recurrence at the studied levels. KEY WORDS: Non-small cell lung cancer, Periostin expression, Clinical significance.

Dynamics of vertical vanadium migration in soil and interactions with indigenous microorganisms adjacent to tailing reservoir.

Severe vanadium pollution in deep soil through surface infiltration during mining activities has been particularly concerned, but little is known about vanadium migration dynamics in vertical soil profile. Indigenous microorganisms widely exist in soil, however, their functions and suffered impacts during vertical vanadium migration have rarely been investigated. In this study, 100 cm height columns were constructed with undisturbed soil around vanadium tailing reservoir were constructed to describe vertical vanadium transport process and corresponding interactions between vanadium and indigenous microorganisms. 91 d continuous leaching with pentavalent vanadium [V(V)] showed that V(V) gradually downward migrated. Soil microorganisms slowed down vertical V(V) migration rate by transferring V(V) to insoluble tetravalent vanadium. Enriched Gemmatimonadaceae and Actinobacteria were identified to contribute to microbial V(V) transformation. Co-existing nitrate weakened the soil's ability to intercept V(V) via electron competition. Microbial communities were reshaped by vanadium during leaching, while enzyme activities increased slightly due to vanadium stimulation. This work advances the understanding of vertical vanadium migration characteristics in soil, which is essential to risk management and effective remediation of vanadium-polluted sites.

Genetic polymorphisms of FCGR2A, ORAI1 and CD40 are associated with risk of lung cancer.

FCGR2A, ORAI1 and CD40 are all involved in the immune and inflammatory responses in the human body, whereas its association with lung cancer is still unclear. This study aimed to investigate the effects of polymorphisms in these genes on the susceptibility to lung cancer. Six candidate single nucleotide polymorphisms (SNPs) were genotyped using a MassARRAY platform in a discovery cohort, including 400 lung cancer patients and 400 healthy controls, and validated in a replication cohort, including 529 lung cancer cases and 532 controls. Comparing the allele frequency distributions, we found that the rs1801274-G, rs511278-T and rs1883832-T were risk alleles for lung cancer (P < 0.05), whereas the minor allele of rs12320939-T was a protective allele for the disease (P = 0.037). Comparing the genotype frequency distributions, we found that rs1801274-GG, rs511278-CT and of rs1883832-TT were risk genotype for lung cancer (P < 0.05). Genetic model analysis showed that the rs1801274 A>G was correlated with an elevated risk of lung cancer in recessive and log-additive models (P < 0.05); rs511278 C>T exhibited an increased risk of disease in dominant and log-additive models (P < 0.05); rs1883832 C>T had a strong relationship with risk of disease in all three models (P < 0.001), whereas rs12320939 G>T was correlated to a reduced risk of disease in recessive and log-additive models (P < 0.05). Finally, the association between the above SNPs and lung cancer risk was validated in a replication cohort (P < 0.05). These results shed new light on the association between immune-related genes and risk of lung cancer, and might be useful for the identification of high-risk individuals.

Soil indigenous microorganisms alleviate soluble vanadium release from industrial dusts.

Vanadium-bearing dusts from industrial processes release abundant toxic vanadium, posing imminent ecological and human health concerns. Although the precipitation of these dusts has been recognized as the main source of soil vanadium pollution, little is known regarding the interrelationships between industrial dusts and soil inherent compositions. In this study, the interactions between dusts from vanadium smelting and soil indigenous microorganisms were investigated. Soluble vanadium (V) [V(V)] released from industrial dusts was reduced by 41.5 ± 0.39% with soil addition, compared to water leaching. Reducible fraction accounted for the highest proportion (55.1 ± 1.73%) of vanadium speciation in the resultant soils, while residual vanadium fraction increased to 83.7 ± 3.22% in the leached dusts. Functional genera (e.g., Aliihoeflea, Actinotalea) that transformed V(V) to insoluble vanadium (IV) alleviated dissolved vanadium release. Nitrate/nitrite reduction and glutathione metabolisms contributed to V(V) immobilization primarily. Structural equation model analysis indicated that V(V) reducers had significant negative impacts on soluble V(V) in the leachate. This first-attempt study highlights the importance of soil microorganisms in immobilizing vanadium from industrial dusts, which is helpful to develop novel strategies to reduce their environmental risks associated to vanadium smelting process.

Optimal Method of Electrical Stimulation for the Treatment of Upper Limb Dysfunction After Stroke: A Systematic Review and Bayesian Network Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: The obstacle of limb motor caused by stroke, especially the decline of motor function of upper limbs, can directly affect the activities of daily living of stroke patients with hemiplegia. Based on long-term clinical practice, the treatment effect of electrical stimulation methods for stroke limb dysfunction has been widely recognized and supported by authoritative guidelines and systematic reviews. However, which electrical stimulation method is the optimum in the treatment of stroke limb dysfunction is still a controversial issue. OBJECTIVE: In this paper, we adopted Network Meta-Analysis (NMA) to rank the priorities of various electrical stimulation methods, so as to select the optimal electrical stimulation method and discuss its rationality in guiding clinical practice. METHODS: We carried out a systematic review by searching a total of 6806 studies from 8 databases and 2 clinical trial registries, and finally screened out 34 studies for further investigation. Then, pairwise meta-analysis and Bayesian network meta-analysis were employed to evaluate the effectiveness and ranking of various interventions. The primary outcome measure was Fugl-Meyer Assessment Upper Extremity (FMA-UE), and the secondary outcome measures were Modified Barthel Index (MBI) and Modified Ashworth Scale (MAS). Finally, the risk of bias, publication bias and sensitivity of the Randomized Controlled Trials (RCTs) were evaluated. RESULTS: On the basis of comprehensive rehabilitation treatment (RT), the Functional Electrical Stimulation (FES) was superior than other electrical stimulation methods in improving both FMA-UE and MBI. Meanwhile, the results indicated that the Transcutaneous Electrical Acupoint Stimulation (TEAS) was the only electrical stimulation method that showed treatment advantages in reducing MAS. CONCLUSION: The study showed that FES had the optimal overall rehabilitation effect on upper limb dysfunction of stroke patients based on the comprehensive RT, while the treatment effect of TEAS on upper limb spasticity after stroke was the most significant.

NOX4-Derived ROS Promotes Collagen I Deposition in Bronchial Smooth Muscle Cells by Activating Noncanonical p38MAPK/Akt-Mediated TGF-ß Signaling.

BACKGROUND: Airway smooth muscle (ASM) remodeling is a hallmark in chronic obstructive pulmonary disease (COPD). NADPH oxidase 4- (NOX4-) mediated reactive oxygen species (ROS) production plays a crucial role in cell differentiation and extracellular matrix (ECM) synthesis in ASM remodeling. However, the precise mechanisms underpinning its pathogenic roles remain elusive. METHODS: The expression of NOX4 and TGF-ß 1 in the airway of the lung was measured in COPD patients and the control group. Cigarette smoke- (CS-) induced emphysema mice were generated, and the alteration of α-SMA, NOX4, TGF-ß 1, and collagen I was accessed. The changes of the expression of ECM markers, NOX4, components of TGF-ß/Smad, and MAPK/Akt signaling in human bronchial smooth muscle cells (HBSMCs) were ascertained for delineating mechanisms of NOX4-mediated ROS production on cell differentiation and remodeling in human ASM cells. RESULTS: An increased abundance of NOX4 and TGF-ß 1 proteins in the epithelial cells and ASM of lung was observed in COPD patients compared with the control group. Additionally, an increased abundance expression of NOX4 and α-SMA was observed in the lungs of the CS-induced emphysema mouse model. TGF-ß 1 displayed abilities to increase the oxidative burden and collagen I production, along with enhanced phosphorylation of ERK, p38MAPK, and p-Akt473 in HBSMCs. These effects of TGF-ß 1 could be inhibited by the ROS scavenger N-acetylcysteine (NAC), siRNA-mediated knockdown of Smad3 and NOX4, and pharmacological inhibitors SB203580 (p38MAPK inhibitor) and LY294002 (Akt inhibitor). CONCLUSIONS: NOX4-mediated ROS production alters TGF-ß 1-induced cell differentiation and collagen I protein synthesis in HBSMCs in part through the p38MAPK/Akt signaling pathway in a Smad-dependent manner.

[Assessment of the hemodynamics of pulmonary artery and right ventricular function in chronic obstructive pulmonary disease with pulmonary hypertension using cardiac magnetic resonance imaging].

OBJECTIVE: To investigate the role of cardiac magnetic resonance imaging (CMRI) in evaluating pulmonary hemodynamics and right ventricular function in patients with chronic obstructive pulmonary disease (COPD) and pulmonary hypertension (PAH); and the relationship between CMRI parameters and pulmonary function parameters, blood gas analysis parameters and 6-minute walk test (6MWT) parameters in patients with COPD complicated with PAH. METHODS: Thirty-seven patients were diagnosed with COPD in the department of respiratory and critical care discipline of Ningxia Medical University General Hospital from October 2013 to October 2016, who underwent transthoracic echocardiography (TTE) to measure pulmonary arterial systolic pressure (PASP), and were divided into COPD group and COPD+PAH group according to whether there was PAH [PASP > 40 mmHg (1 mmHg = 0.133 kPa) was defined as PAH]. All patients completed pulmonary function tests [1 second forced expiratory volume to forced vital capacity ratio (FEV1/FVC), FEV1 predicted value (FEV1pred)], blood gas analysis [arterial blood oxygen partial pressure (PaO2), arterial blood carbon dioxide partial pressure (PaCO2)], CMRI examination [relative dilatation of the main pulmonary artery (mPAD), mean pulmonary artery pressure (mPAP), left ventricular ejection fraction (LVEF), right ventricular ejection fraction (RVEF), right ventricular end-diastolic myocardial mass (RVMED), right ventricular end-systolic myocardial mass (RVMES)], and 6MWD [6-minute walk distance (6MWD)] within 1 week. The obtained clinical parameters had been compared between the groups, and correlation was analyzed. RESULTS: Among the 37 patients with COPD, 16 patients were complicated with PAH. There were no significant differences in FEV1/FVC, FEV1pred, PaO2, PaCO2 and other baseline indicators between the two groups. In the COPD group, TTE obtained PASP of 2 patients were normal (PSAP < 40 mmHg), while CMRI measured mPAP were higher than the normal limit (> 25 mmHg). Compared with the COPD group, mPAD, RVEF and 6MWD were significantly decreased in the COPD+PAH group [mPAD: (25.64±5.01)% vs. (44.00±22.52)%, RVEF: 0.525±0.054 vs. 0.592±0.071, 6MWD (m): 319.3±116.5 vs. 408.2±38.0, all P < 0.01], mPAP, RVMED and RVMES were significantly increased [mPAP (mmHg): 28.89±3.16 vs. 20.18±2.43, RVMED (g): 57.19±15.46 vs. 40.71±15.44, RVMES (g): 45.99±11.16 vs. 33.71±13.39, all P < 0.01], and there was no significant differences in LVEF (0.663±0.082 vs. 0.699±0.075, P > 0.05). Correlation analysis showed that mPAD was positively correlated with FEV1/FVC and FEV1pred (r1 = 0.538, P1 = 0.021; r2 = 0.448, P2 = 0.049); RVMED was negatively correlated with PaO2 (r = -0.581, P = 0.015), and positively correlated with PaCO2 (r = 0.592, P = 0.014); 6MWD was positively correlated with RVEF (r = 0.485, P = 0.041), and had no correlation with LVEF (r = 0.271, P = 0.104). CONCLUSIONS: Compared with COPD patients, changes in pulmonary hemodynamics and right ventricular function in COPD patients with PAH are related to the severity of airflow limitation. CMRI can early monitor pulmonary hemodynamics and right heart function changes in patients with COPD. Once PAH appears, pulmonary hemodynamics, right heart function and exercise tolerance have changed.

Morin attenuates cigarette smoke-induced lung inflammation through inhibition of PI3K/AKT/NF-κB signaling pathway.

Cigarette smoke (CS) is a major factor that leads to lung inflammation. The prevalence of CS-induced lung injury has continuously increased worldwide. Morin exists in a large member of plants and fruits that has been reported to have antioxidant and anti-inflammatory properties. In the present study, we tested the mechanism and protective effects of morin on CS-induced lung inflammation in mice. The mice were exposed to CS for 2 h twice a day for 4 weeks. Morin (10, 20, and 40 mg/kg) was treated to mice through oral gavage 1 h before CS administration. 24 h after the last CS exposure, the mice were euthanized. The lung tissues were collected and the pathological changes, wet/dry ratio, MPO activity, MDA levels, and P13K/ATK/NF-κB signaling pathway expression were detected. The bronchial alveolar lavage fluid (BALF) was obtained and the levels of inflammatory cells and inflammatory cytokines were measured. The results showed that morin treatment significantly inhibited lung pathological changes, wet/dry ratio, MPO activity, and MDA level. The levels of total cells, neutrophils, macrophages, as well as the production of inflammatory cytokines in the BALF induced by CS were also suppressed by morin. Further research showed that morin dramatically suppressed the activation of P13K/ATK/NF-κB singling pathway induced by CS. This study highlights the protective effects of morin on CS-induced lung inflammation, which may, at least part, be mediated through inhibiting P13K/ATK/NF-κB signaling pathway. These finding demonstrated that morin could be a potential drug for CS-induced lung injury.

Combining Carcinoembryonic Antigen and Platelet to Lymphocyte Ratio to Predict Brain Metastasis of Resected Lung Adenocarcinoma Patients.

We aimed to evaluate the role of pretreatment carcinoembryonic antigen (CEA) and platelet to lymphocyte ratio (PLR) in predicting brain metastasis after radical surgery for lung adenocarcinoma patients. The records of 103 patients with completely resected lung adenocarcinoma between 2013 and 2014 were reviewed. Clinicopathologic characteristics of these patients were assessed in the Cox proportional hazards regression model. Brain metastasis occurred in 12 patients (11.6%). On univariate analysis, N2 stage (P = 0.013), stage III (P = 0.016), increased CEA level (P = 0.006), and higher PLR value (P = 0.020) before treatment were associated with an increased risk of developing brain metastasis. In multivariate model analysis, CEA above 5.2 ng/mL (P = 0.014) and PLR ≥ 120 (P = 0.036) remained as the risk factors for brain metastasis. The combination of CEA and PLR was superior to CEA or PLR alone in predicting brain metastasis according to the receiver operating characteristic (ROC) curve analysis (area under ROC curve, AUC 0.872 versus 0.784 versus 0.704). Pretreatment CEA and PLR are independent and significant risk factors for occurrence of brain metastasis in resected lung adenocarcinoma patients. Combining these two factors may improve the predictability of brain metastasis.

Sox2 inhibits Wnt-ß-catenin signaling and metastatic potency of cisplatin-resistant lung adenocarcinoma cells.

Lung cancer remains one of the most common cancer-associated mortalities worldwide, and platinum-based doublet chemotherapies are recommended as the first­line treatment for advanced non­small cell lung cancer (NSCLC). However, the frequent development of multidrug resistance, to cisplatin regimens in particular, is a major cause of chemotherapy failure in patients with aggressive NSCLC. Wnt/ß­catenin signaling and sex­determining region Y box 2 (Sox2) have been implicated in the development and progression and resistance to epidermal growth factor receptor­targeting therapy in lung cancer. The present study aimed to explore the effects of Wnt/ß­catenin and Sox2 signaling on the chemoresistance of cisplatin­resistant lung cancer cells by assessing the effects of Sox2 on Wnt/ß­catenin signaling activity, cell migration, invasion and clonogenicity, and susceptibility to cisplatin in lung adenocarcinoma A549 cells and cisplatin-resistant A549/DDP cells. The results demonstrated that an enforced expression of Sox2 led to inhibition of Wnt/ß-catenin signaling activity, potentially by upregulating glycogen synthase kinase 3 ß in A549 and A549/DDP cells. An overexpression of Sox2 promoted cell migration and invasion, in addition to enhancing the clonogenic capacity in A549 cells. Notably, knockdown Sox2 using short hairpin RNA led to an enhanced susceptibility of A549 and A549/DDP cells to cisplatin, along with increased cell apoptosis. The present study thus suggests that Sox2 may be an important regulator in development of chemoresistance of lung cancer cells and may be a novel therapeutic target for treatment chemoresistant lung cancer.