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To evaluate the effect of acute high-altitude exposure on sensory and short-term memory using interactive software, we transported 30 volunteers in a sport utility vehicle to a 4280 m plateau within 3 h. We measured their memory performance on the plain (initial arrival) and 3 h after arrival on the plateau using six measures. Memory performance was significantly poorer on the plateau by four of the six measures. Furthermore, memory performance was significantly poorer in the acute mountain sickness (AMS) group than in the non-AMS group by five of the six measures. These findings indicate that rapid ascent to 4280 m and remaining at this altitude for 3 h resulted in decreased sensory and short-term memory, particularly among participants who developed AMS. [ABSTRACT FROM AUTHOR]

CXC chemokines and their cognate receptors have been implicated wildly in cancer pathogenesis. In the present study, we report a critical cause relationship between CXCR4 expression and tumorigenesis in the setting of human esophageal squamous cell carcinoma (ESCC). In ESCC cells, CXCR4 expression was significantly higher than in human esophageal epithelial cells (HEEC). Reduction of CXCR4 in ESCC cells reduced cell proliferation and invasion in vitro and tumor growth in vivo. Among the potential downstream targets of CXCR4-CXCL12 are RhoA, Rac-1, and Cdc42, which are likely to contribute to the invasiveness of ESCC cells. Finally, we found that CXCR4-CXCL12/AKT axis regulates RhoA, Rac-1, and Cdc42 to modulate cell invasion and tumor metastasis. Together, these results demonstrate a role for CXCR4 in ESCC metastasis and progression and suggest potential targets for therapeutic intervention. [ABSTRACT FROM AUTHOR]

Objectives Esophageal squamous cell carcinoma is one of the most frequent malignant tumors. Cancer stem cells are considered to be responsible for tumor growth, metastasis, and recurrence. Cluster of differentiation 133 (CD133) and C-X-C chemokine receptor type 4 (CXCR4) are frequently applied markers for the identification and isolation of cancer stem cells. However, few studies have investigated the coexpression of CD133 and CXCR4 in esophageal squamous cell carcinoma. This study aims to explore the clinical and biological role of stem-like CD133 + CXCR4 + cells in esophageal squamous cell carcinoma. Methods Immunohistochemical staining was performed to detect the expression of CD133 and CXCR4 in esophageal squamous cell carcinoma tissues of patients. Flow cytometry and fluorescence-activated cell sorting were applied to analyze and isolate each subgroup in esophageal squamous cell carcinoma cell line TE-1. The characteristic differences between each subgroup were assayed in vitro. The association between CD133/CXCR4 expression and patients' prognosis was analyzed by Kaplan–Meier and Cox regression. Results Among 154 patient tissues, concomitant high CD133-CXCR4 expression accounts for 20.78% (32/154). In vitro, CXCR4 + cells (CD133 + CXCR4 + and CD133 − CXCR4 + ) showed high invasive potential and CD133 + CXCR4 + cells showed high proliferative capacity. Clinically, patients with concomitant high CD133-CXCR4 expression had decreased disease-free survival and overall survival ( P < .01). Conclusions Esophageal squamous cell carcinoma cells coexpressing CD133 and CXCR4 possess the characteristics of cancer stem cells. The concomitant high CD133-CXCR4 expression might be a novel marker for predicting the poor prognosis of patients with esophageal squamous cell carcinoma, and CD133 and CXCR4 may serve as potential therapeutic targets. [ABSTRACT FROM AUTHOR]

The expression of calpain small subunit 1 (Capn4) is correlated with the invasion of several types of tumors. However, the roles of Capn4 in non-small cell lung cancer (NSCLC) remain unclear. In this study, we found that the expression of Capn4 in NSCLC tissues was much higher than that in nontumorous samples. High levels of Capn4 expression were associated with lymph node metastasis and large tumor size in NSCLC patients. The 5-year overall survival rate in the Capn4 group was significantly lower than that in the Capn4 group. In multivariate analysis, Capn4 was identified as an independent prognostic factor for overall survival. Moreover, in an in vitro analysis, downregulation of Capn4 expression by siRNA suppressed the invasive potential of lung cancer cells. Finally, we demonstrated that Capn4 enhanced the invasion ability of lung cancer cells by upregulating the expression of matrix metalloproteinase 2. Our findings indicated that Capn4 may represent a potential therapeutic target and a novel prognostic marker of NSCLC. [ABSTRACT FROM AUTHOR]

In non-small cell lung cancer (NSCLC), both USP7 expression and p53 gene status were reported to be an indicator of poor prognosis in adenocarcinoma patients; however, its roles and mechanisms in lung squamous cell carcinoma and large cell carcinoma need to be clarified. The USP7 expression was examined in NSCLC tumors (excluding adenocarcinoma), their corresponding non-tumorous tissues, and NSCLC cells. Then, the prognostic role of USP7 was analyzed in 110 NSCLC samples (excluding the adenocarcinoma). Finally, the roles and mechanisms of USP7 in the proliferation, metastasis, and invasion of a NSCLC cell were assessed using a specific vshRNA. The USP7 expression was higher in NSCLC tissues compared to non-tumorous samples, accordingly, the high level of USP7 was detected in NSCLC cell lines compared with HBE cell. After the USP7 downregulation, the H460 cells exhibited decreased metastasis/invasion in vitro and in vivo. The preliminary mechanism study indicated overexpression of USP7 might regulate the p53-MDM2 pathway by inducing the MDM2 de-ubiquitination and subsequent stabilization, which resulted in the upregulation of the Bad phosphorylation. Additionally, we also found that USP7 might induce cell epithelial-mesenchymal transition to enhance the cell invasive ability. Clinically, USP7 overexpression significantly correlated with malignant phenotype. Furthermore, the 5-year overall survival in patients with USP7 was higher than that of USP7. Multivariate analysis showed USP7 overexpression was an independent prognostic marker for these cancers. USP7 overexpression may regulate the survival and invasive properties of squamous cell carcinoma and large cell carcinoma cells, and may serve as a molecular target. [ABSTRACT FROM AUTHOR]

Tumor recurrence and metastasis after surgery are the leading causes of death in patients with esophageal squamous cell carcinoma (ESCC). Next-generation sequencing techniques have improved our understanding of the genetic alterations underlying tumor initiation and progression. To explore recurrence-specific transcriptional profiles, functional properties, and gene co-expression networks in ESCC, samples from recurrence ( n = 4) and nonrecurrence ( n = 4) groups were analyzed by RNA sequencing. Patients included in the nonrecurrence group had five or more years of survival without any evidence of recurrence or metastasis, while those included in the recurrence group exhibited early recurrence and metastasis and died within 2 years. We identified 533 significantly differentially expressed protein-coding and noncoding genes. Functional enrichment analysis indicated that ESCC recurrence was related to dysregulated cell-cell adherence, microenvironment homeostasis, information processing, and the immune response. Co-expression networks demonstrated differences in the patterns of gene expression and co-expression between the recurrence and nonrecurrence groups. This study provided important insights into ESCC progression and the differentially expressed genes that may represent potential targets for ESCC diagnosis and therapy. [ABSTRACT FROM AUTHOR]

Radiation distribution in a photoreactor with multiple mediums is solved by the P-1 model. The UV lamp is included in the computational domain. An additional source term method is presented to describe the generation of UV light, which can avoid the use of analytical lamp emission model at the lamp surface. The boundary condition for incident radiation at the semi-transparent wall between adjacent mediums has been derived to link the P-1 equations in adjacent mediums, which enables the present model to adapt to the photoreactor with complicated structure. The predicted incident radiation agrees well with the experimental data in literature. The effects of absorption coefficient, scattering coefficient and phase function of lamp plasma on the radiation distribution are discussed in detail. [ABSTRACT FROM AUTHOR]

The 5p15.33 locus has been recently identified to associate with multiple cancer types including lung, urinary bladder, prostate, and cervical cancer, based on its critical role in the maintenance of telomere, chromosome stability, and ultimately preventing normal cell malignance. TERT (human telomerase reverse transcriptase) is an attractive candidate gene for the 5p15.33 locus. Recently, a number of case-control studies have been carried out to investigate the relationship between the rs2736100 polymorphism in TERT and genetic susceptibility to lung cancer. However, the results have been inconclusive. To investigate this inconsistency and derive a more precise estimation of the relationship, we conducted a comprehensive meta-analysis of 56,223 cases and 86,680 controls from 22 published studies. Using the random-effects model, we found a significant association between rs2736100 polymorphism and lung cancer risk with per-allele OR of 1.20 (95 % CI, 1.16-1.23; P < 10). Significant results were also observed using dominant and recessive genetic model. Significant results were found in East Asians and Caucasians when stratified by ethnicity in all genetic models. In addition, our data indicate that rs2736100 is involved in lung cancer susceptibility and confer its effect primarily in adenocarcinoma in the subgroup analyses by histological subtype. In the stratified analysis according to sample size, smoking behavior, sex, and age, risks significantly increased for the polymorphism. In conclusion, this meta-analysis demonstrated that TERT rs2736100 polymorphism is a risk factor associated with increased lung cancer susceptibility, particularly for lung adenocarcinoma. [ABSTRACT FROM AUTHOR]

BACKGROUND The 14-3-3ζ protein has been identified as a putative oncoprotein in several cancers, including non-small cell lung cancer (NSCLC). However, the mechanisms underlying its functions have not been well defined. METHODS Proteins that interact with 14-3-3ζ were identified through coimmunoprecipitation and mass spectrometry in NSCLC cells. The interaction of 14-3-3ζ with these molecular partners and their roles in the invasiveness and metastasis of NSCLC cells were assayed through specific disruptions in the 14-3-3ζ signaling network. In addition, the clinical implications of this 14-3-3ζ complex were examined in samples from patients with NSCLC. RESULTS Among the identified proteins that interacted with 14-3-3ζ, there were 230 proteins in 95-D cells, 181 proteins in 95-C cells, and 203 proteins in A549 cells; and 16 interacting proteins were identified that overlapped between all cell lines. Further studies revealed 14-3-3ζ complexes within the heat shock protein 27 (Hsp27) protein and demonstrated that the interference of Hsp27 or 14-3-3ζ inhibited the invasion and metastasis of NSCLC cells. The invasive and metastatic capabilities of cells with both Hsp27 and 14-3-3ζ interference could be completely restored only by Hsp27 and 14-3-3ζ complementary DNA transfection and not by either agent alone. Clinically, the postoperative 5-year overall survival (OS) in patients who had high expression of both 14-3-3ζ and Hsp27 was significantly lower than the 5-year OS in patients who had low expression of both 14-3-3ζ and Hsp27 (26.5% vs 59.7%, respectively). Multivariate analysis revealed that the combined expression of 14-3-3ζ and Hsp27 was an independent prognostic indicator of OS ( P = .036). CONCLUSIONS The current data suggest that the combined expression of 14-3-3ζ and Hsp27 may be a biomarker for predicting survival in patients with NSCLC, and this combination may have potential as a therapeutic target for NSCLC. Cancer 2014;120:652-663. © 2013 American Cancer Society. [ABSTRACT FROM AUTHOR]

Integrin β4 and its Y-1494 phosphorylation play an important role in cell signaling. We found a small molecule, ethyl1-(3-(4-chlorophenoxy)-2-hydroxypropyl)-3-(4-chlorophenyl)-1 H-pyrazole-5-carboxylate (ECPC), that could elevate the levels of KIT ligand (KITLG), interleukin 8 (IL-8), prostaglandin-endoperoxide synthase 2 (PTGS2) and activating transcription factor 3 (ATF3) and promote apoptosis in vascular endothelial cells (VECs) through integrin β4. We investigated the underlying mechanism of integrin β4 participating in this process. ECPC treatment increased the phosphorylation of Y-1494 in the integrin β4 cytoplasmic domain via a well-known receptor tyrosine kinase, fibroblast growth factor receptor 1 (FGFR1), and integrin β4 translocated from the cytoplasm to nucleus. With suppression of Y-1494 phosphorylation by FGF-2 or siRNA of FGFR1, ECPC failed to promote integrin β4 nuclear translocation and could not increase the expression of KITLG, IL-8, PTGS2 or ATF3. Y-1494 phosphorylation and nuclear translocation of integrin β4 may be important during ECPC-induced apoptosis in VECs. [ABSTRACT FROM AUTHOR]

A double-exponential surface sink model for VOCs sorption on building materials is presented. Here, the diffusion of VOCs in the material is neglected and the material is viewed as a surface sink. The VOCs concentration in the air adjacent to the material surface is introduced and assumed to always maintain equilibrium with the materialphase concentration. It is assumed that the sorption can be described by mass transfer between the room air and the air adjacent to the material surface. The mass transfer coefficient is evaluated from the empirical correlation, and the equilibrium constant can be obtained by linear fitting to the experimental data. The present model is validated through experiments in small and large test chambers. The predicted results accord well with the experimental data in both the adsorption stage and desorption stage. The model avoids the ambiguity of model constants found in other surface sink models and is easy to scale up. [ABSTRACT FROM AUTHOR]

Acute exposure to high altitudes can cause neurological dysfunction due to decreased oxygen availability to the brain. In this study, the protective effects of Huperzine A on cognitive deficits along with oxidative and apoptotic damage, due to acute hypobaric hypoxia, were investigated in male Sprague-Dawley rats. Rats were exposed to simulated hypobaric hypoxia at 6,000 m in a specially fabricated animal decompression chamber while receiving daily Huperzine A orally at the dose of 0.05 or 0.1 mg/kg body weight. After exposure to hypobaric hypoxia for 5 days, rats were trained in a Morris Water Maze for 5 consecutive days. Subsequent trials revealed Huperzine A supplementation at a dose of 0.1 mg/kg body weight restored spatial memory significantly, as evident from decreased escape latency and path length to reach the hidden platform, and the increase in number of times of crossing the former platform location and time spent in the former platform quadrant. In addition, after exposure to hypobaric hypoxia, animals were sacrificed and biomarkers of oxidative damage, such as reactive oxygen species, lipid peroxidation, lactate dehydrogenase activity, reduced glutathione, oxidized glutathione and superoxide dismutase were studied in the hippocampus. Expression levels of pro-apoptotic proteins (Bax, caspase-3) and anti-apoptotic protein (Bcl-2) of hippocampal tissues were evaluated by Western blotting. There was a significant increase in oxidative stress along with increased expression of apoptotic proteins in hypoxia exposed rats, which was significantly improved by oral Huperzine A at 0.1 mg/kg body weight. These results suggest that supplementation with Huperzine A improves cognitive deficits, reduces oxidative stress and inhibits the apoptotic cascade induced by acute hypobaric hypoxia. [ABSTRACT FROM AUTHOR]

Aim:In vascular strips, the adjacent endothelial cells modulate the contraction of vascular smooth muscle cells (VSMCs) induced by sphingosylphosphorylcholine (SPC) through nitric oxide (NO). The aim of this study was to elucidate the mechanisms by which vascular endothelial cells (VECs) reduce the SPC-induced contraction of VSMCs in a co-culture system.Methods:Human umbilical VECs and VSMCs were co-cultured. The VECs were transfected with integrin β4- or Fyn-specific siRNA. The areas of VSMCs that are involved in cell contractility were quantified using the Leica confocal software and collagen contractility assay. The production of NO in VECs was measured in the cell supernatants using NO Detection Kit. The levels of integrin β4 and Fyn in VECs and the levels of Rho kinase (ROCK) in VSMC were detected using immunofluorescence assays or Western blots.Results:Co-culture with VECs reduced the contraction of VSMCs induced by SPC (30 μmol/L). The down-regulation of integrin β4 or Fyn in VECs by the specific siRNA (20 nmol/L) was able to counteract the effects of VECs on the SPC-induced VSMC contractions. Furthermore, the integrin β4-specific siRNA (20 and 40 nmol/L) significantly reduced the level of Fyn protein and the production of NO in VECs, while increased the level of ROCK in VSMCs that had been stimulated by SPC.Conclusion:The VECs reduced the SPC-induced contraction of VSMCs in the co-culture system through integrin β4 and Fyn proteins. In this process, NO may be the factor downstream of integrin β4 in VECs, while ROCK may be the key protein regulating the contraction of VSMCs. [ABSTRACT FROM AUTHOR]

Intramuscular electromyography (EMG) signals are usually decomposed with semiautomatic procedures that involve the interaction with an expert operator. In this paper, a Bayesian statistical model and a maximum a posteriori (MAP) estimator are used to solve the problem of multiunit EMG decomposition in a fully automatic way. The MAP estimation exploits both the likelihood of the reconstructed EMG signal and some physiological constraints, such as the discharge pattern regularity and the refractory period of muscle fibers, as prior information integrated in a Bayesian framework. A Tabu search is proposed to efficiently tackle the nondeterministic polynomial-time-hard problem of optimization w.r.t the motor unit discharge patterns. The method is fully automatic and was tested on simulated and experimental EMG signals. Compared with the semiautomatic decomposition performed by an expert operator, the proposed method resulted in an accuracy of 90.0%±3.8% when decomposing singlechannel intramuscular EMG signals recorded from the abductor digiti minimi muscle at contraction forces of 5% and 10% of the maximal force. The method can also be applied to the automatic identification and classification of spikes from other neural recordings. [ABSTRACT FROM AUTHOR]

Treatment of various types of cells with the mitochondrial ATP-sensitive K+ channel opener, diazoxide, preconditions cells to subsequent injuries and inhibits apoptosis. However, the role and mechanism(s) of diazoxide in solid tumor cell growth are largely unknown. Here we demonstrate that diazoxide inhibited the proliferation of lung cancer cells as well as the transcription of cell cycle-related protein Cyclin D1. Cyclin D1 overexpression inhibited the negative role of diazoxide in cell cycle progression. We further explored the mechanisms by which diazoxide affected Cyclin D1 transcription and found that the β-catenin transcription factor was downregulated by diazoxide, with a corresponding decrease in Cyclin D1 promoter activity. Taken together, these results suggest that diazoxide inhibits lung cancer cell proliferation via downregulation of Cyclin D1 transcription, which may have important therapeutic implications in lung cancer patients. [ABSTRACT FROM AUTHOR]

The toll-like receptor (TLR) family is an important class of proteins involved in the immune response. However, little is known about the association between TLRs and Esophageal squamous cell cancer (ESCC). We explored differentially expressed genes (DEGs) between ESCC and esophagus tissues in TCGA and GTEx database. By taking the intersection with TLR gene set and using univariate Cox analysis and multivariate Cox regression analysis to discriminate the hub genes, we created a TLR-prognostic model. Our model separated patients with ESCC into high- and low-risk score (RS) groups. Prognostic analysis was performed with Kaplan–Meier curves. The two groups were also compared regarding tumor immune microenvironment and drug sensitivity. Six hub genes (including CD36, LGR4, MAP2K3, NINJ1, PIK3R1, and TRAF3) were screened to construct a TLR-prognostic model. High-RS group had a worse survival (p < 0.01), lower immune checkpoint expression (p < 0.05), immune cell abundance (p < 0.05) and decreased sensitivity to Epirubicin (p < 0.001), 5-fluorouracil (p < 0.0001), Sorafenib (p < 0.01) and Oxaliplatin (p < 0.05). We constructed a TLR-based model, which could be used to assess the prognosis of patients with ESCC, provide new insights into drug treatment for ESCC patients and investigate the TME and drug response. [ABSTRACT FROM AUTHOR]

Cancerous genetic mutations result in a complex and comprehensive post-translational modification (PTM) dynamics, in which protein succinylation is well known for its ability to reprogram cell metabolism and is involved in the malignant evolution. Little is known about the regulatory interactions between succinylation and other PTMs in the PTM network. Here, we developed a conjoint analysis and systematic clustering method to explore the intermodification communications between succinylome and phosphorylome from eight lung cancer patients. We found that the intermodification coorperation in both parallel and series. Besides directly participating in metabolism pathways, some phosphosites out of mitochondria were identified as an upstream regulatory modification directing succinylome dynamics in cancer metabolism reprogramming. Phosphorylated activation of histone deacetylase (HDAC) in lung cancer resulted in the removal of acetylation and favored the occurrence of succinylation modification of mitochondrial proteins. These results suggest a tandem regulation between succinylation and phosphorylation in the PTM network and provide HDAC-related targets for intervening mitochondrial succinylation and cancer metabolism reprogramming. [ABSTRACT FROM AUTHOR]

Chinese mitten crabs (Eriocheir japonica sinensis) are catadromous, spending most of their lives in fresh water, but moving to a mixed salt-fresh water environment for reproduction. The characteristics of this life history might imply a rapidly evolutionary transition model for adaptation to marine from freshwater habitats. In this study, transcriptome-wide identification and differential expression on Chinese mitten crab groups were analysed. Results showed: clean reads that were obtained totalled 93,833,096 (47,440,998 in Group EF, the reference, and 46,392,098 in Group ES, the experimental) and 14.08G (7.12G in Group EF 6.96G in Group ES); there were 11,667 unigenes (15.29%) annotated, and they were located to 230 known KEGG pathways in five major categories; in differential expression analysis, most of the top 20 up-regulated pathways were connected to the immune system, disease, and signal transduction, while most of the top 20 down-regulated pathways were related to the metabolism system; meanwhile, 8 representative osmoregulation-related genes (14-3-3 epsilon, Cu2+ transport ATPase, Na+/K+ ATPase, Ca2+ transporting ATPase, V-ATPase subunit A, Putative arsenite-translocating ATPase, and Cation transport ATPase, Na+/K+ symporter) showed up-regulation, and 1 osmoregulation-related gene (V-ATPase subunit H) showed down-regulation. V-ATPase subunit H was very sensitive to the transition of habitats. These results were consistent with the tests of qRT-PCR. The present study has provided a foundation to further understand the molecular mechanism in response to salinity changing in water.

Se presenta un caso de una paciente con síndrome metabólico y comorbilidades asociadas que acude a un consultorio farmacéutico del nivel primario de Atención en Salud en Bogotá (Colombia), donde recibe seguimiento farmacoterapéutico. La paciente usa tratamientos prescritos por sus médicos y se automedica con productos naturales, como son el extracto de balsamina para regular niveles de glucosa, el extracto de arándano azul europeo para problemas oculares y el uso de lecitina de soja para control de triglicéridos. Para la evaluación de la farmacoterapia, se localizó evidencia científica sobre el uso y conveniencia de cada producto en el tratamiento de sus problemas de salud, realizándose las siguientes intervenciones: continuar con la toma de la balsamina, el Bilberry y la lecitina de soja, ya que existen reportes de su utilidad como coadyuvantes en el control de las enfermedades que presenta y la elaboración de un plan de medicación para reforzar la adherencia a los tratamientos. Cuando se evalúan las intervenciones, encontramos que las cifras de glicemia, presión arterial y función hepática se encuentran dentro de objetivos terapéuticos. En este caso, el químico farmacéutico tiene una labor integradora de las terapias de los pacientes, basados en la valoración del riesgo-beneficio y a través del seguimiento farmacoterapéutico obtiene información clínica que permite tomar decisiones sustentadas para el futuro, más aún en el contexto de Latinoamérica, donde los productos naturales son ampliamente usados en la población.

Background: Data mining of The Cancer Genome Atlas (TCGA) data has significantly facilitated cancer genome research and provided unprecedented opportunities for cancer researchers. However, existing web applications for DNA methylation analysis does not adequately address the need of experimental biologists, and many additional functions are often required. Results: To facilitate DNA methylation analysis, we present the SMART (Shiny Methylation Analysis Resource Tool) App, a user-friendly and easy-to-use web application for comprehensively analyzing the DNA methylation data of TCGA project. The SMART App integrates multi-omics and clinical data with DNA methylation and provides key interactive and customized functions including CpG visualization, pan-cancer methylation profile, differential methylation analysis, correlation analysis and survival analysis for users to analyze the DNA methylation in diverse cancer types in a multi-dimensional manner. Conclusion: The SMART App serves as a new approach for users, especially wet-bench scientists with no programming background, to analyze the scientific big data and facilitate data mining. The SMART App is available at http://www.bioinfo-zs.com/smartapp. [ABSTRACT FROM AUTHOR]