Lung cancer is the most commonly diagnosed cancer worldwide, and metastasis in lung cancer is the leading cause of cancer‐related deaths. Thus, understanding the mechanism of lung cancer metastasis ...will improve the diagnosis and treatment of lung cancer patients. Herein, we found that expression of cluster of differentiation 109 (CD109) was correlated with the invasive and metastatic capacities of lung adenocarcinoma cells. CD109 is upregulated in tumorous tissues, and CD109 overexpression was associated with tumor progression, distant metastasis, and a poor prognosis in patient with lung adenocarcinoma. Mechanistically, expression of CD109 regulates protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling via its association with the epidermal growth factor receptor (EGFR). Inhibition of CD109 decreases EGFR phosphorylation, diminishes EGF‐elicited activation of AKT/mTOR, and sensitizes tumor cells to an EGFR inhibitor. Taken together, our results show that CD109 is a potential diagnostic and therapeutic target in lung cancer patients.
CD109 promotes lung cancer metastasis through promoting EGFR‐AKT‐mTOR signaling and CD109 is an independent prognostic marker for lung adenocarcinoma.
Tumor metastasis is the leading cause of death in cancer patients. Identifying metastatic biomarkers in tumor cells would help cancer diagnoses and the development of therapeutic targets. ...Yes-associated protein (YAP) plays an important role in organ development and has gained much attention in tumorigenesis. However, the role of YAP and the underlying mechanism in tumor metastasis of colorectal cancer (CRC) is still unclear. In this study, we generated metastatic 116-LM cells from the HCT116 CRC cell line. We found that the capacity for tumor aggressiveness was elevated in 116-LM cells and identified that YAP and its mRNA level were upregulated in 116-LM cells. Moreover, expression of YAP was found to correlate with epithelial-mesenchymal transition (EMT) marker expressions, whereas suppression of YAP decreased EMT marker expressions and impeded tumor migration and invasion. Additionally, upregulation of YAP was identified in colon cancer patients, and it was correlated with EMT gene expressions. Furthermore, we identified LBH589, a histone deacetylase inhibitor, that was capable of inhibiting tumor growth and aggressiveness in both HCT116 and 116-LM cells. LBH589 potentially inhibited YAP and its mRNA expression, accompanied by diminished expressions of YAP downstream genes and EMT markers. Together, YAP plays a crucial role in aggressiveness and metastasis of CRC, and YAP may be an attractive therapeutic target.
•Overexpression of YAP regulates epithelial-mesenchymal transition and aggressiveness in colorectal cancer.•LBH589 suppresses tumor growth and invasiveness.•LBH589 downregulates YAP and downstream signaling.
Colon cancer is the third most common cancer in the world and the second most common cause of cancer-related mortality. Molecular biomarkers for colon cancer have undergone vigorous discovery and ...validation. Recent studies reported that overexpression of podocalyxin-like protein 1 (PODXL) is associated with distant metastasis and poor prognosis across several types of malignancies. Its role and underlying molecular mechanism, however, are not yet fully understood. In the present study, we revealed that the Hippo transducer, the transcriptional coactivator with PDZ-binding motif (TAZ), acts as a downstream mediator of PODXL in colon cancer. Inhibition of PODXL resulted in the suppression of TAZ signaling and the downregulation of Hippo downstream genes. Moreover, PODXL plays a critical role in cancer stemness, invasiveness, and sensitivity to chemotherapies in colon cancer HCT15 cells. Notably, expression of PODXL showed a positive correlation with stem-like and epithelial-mesenchymal transition (EMT) core signatures, and was associated with poor survival outcomes in patients with colon cancer. These findings provide novel insights into the molecular mechanism of PODXL-mediated tumorigenesis in colon cancer.
Dynamic modeling of a wave glider Zhou, Chun-lin; Wang, Bo-xing; Zhou, Hong-xiang ...
Frontiers of information technology & electronic engineering,
09/2017, Volume:
18, Issue:
9
Journal Article
Peer reviewed
We propose a method to establish a dynamic model for a wave glider, a wave-propelled sea surface vehicle that can make use of wave energy to obtain thrust. The vehicle, composed of a surface float ...and a submerged glider in sea water, is regarded as a two-particle system. Kane＇s equations are used to establish the dynamic model. To verify the model, the design of a testing prototype is proposed and pool trials are conducted. The speeds of the vehicle under different sea conditions can be computed using the model, which is verified by pool trials. The optimal structure parameters useful for vehicle designs can also be obtained from the model. We illustrate how to build an analytical dynamics model for the wave glider, which is a crucial basis for the vehicle＇s motion control. The dynamics model also provides foundations for an off-line simulation of vehicle performance and the optimization of its mechanical designs.
Let（X,d,）be a metric measure space satisfying both the geometrically doubling and the upper doubling conditions.Let ρ∈（1,∞）,0〈p≤1≤q≤∞,p≠q,γ∈1,∞）and ∈ ∈（0,∞）.In this paper,the authors introduce the ...atomic Hardy space Hp,q,γ atb,ρ（μ）and the molecular Hardy space Hp,q,γ,mb,ρ ∈（μ）via the discrete coefficient K（ρ）,p B,S,and prove that the Calder′on-Zygmund operator is bounded from Hp,q,γ,δmb,ρ（μ）（or Hp,q,γatb,ρ（μ））into Lp（μ）,and from Hp,q,γ＋1atb,ρ（ρ＋1）（μ）into H p,q,γ,12（δ-νp＋ν）mb,ρ（μ）.The boundedness of the generalized fractional integral Tβ（β∈（0,1））from Hp1,q,γ,θmb,ρ（μ）（or Hp1,q,γatb,ρ（μ））into Lp2（μ）with 1/p2=1/p1-β is also established.The authors also introduce theρ-weakly doubling condition,withρ∈（1,∞）,of the measure and construct a non-doubling measure satisfying this condition.If isρ-weakly doubling,the authors further introduce the Campanato space Eα,qρ,η,γ（μ）and show that Eα,qρ,η,γ（μ）is independent of the choices ofρ,η,γand q;the authors then introduce the atomic Hardy space Hp,q,γatb,ρ（μ）and the molecular Hardy space Hp,q,γ,mb,ρ（μ）,which coincide with each other;the authors finally prove that Hp,q,γatb,ρ（μ）is the predual of E1/p-1,1ρ,ρ,1（μ）.Moreover,if is doubling,the authors show that Eα,qρ,η,γ（μ）and the Lipschitz space Lipα,q（μ）（q∈1,∞））,or Hp,q,γatb,ρ（μ）and the atomic Hardy space Hp,q at（μ）（q∈（1,∞）of Coifman and Weiss coincide.Finally,if（X,d,）is an RD-space（reverse doubling space）with（X）=∞,the authors prove that Hp,q,γatb,ρ（μ）,Hp,q,γ,mb,ρ（μ）and Hp,q at（μ）coincide for any q∈（1,2.In particular,when（X,d,）：=（RD,｜｜,dx）with dx being the D-dimensional Lebesgue measure,the authors show that spaces Hp,q,γatb,ρ（μ）,Hp,q,γ,mb,ρ（μ）,Hp,q,γatb,ρ（μ）and Hp,q,γ,mb,ρ（μ）all coincide with Hp（RD）for any q∈（1,∞）.
Rheumatoid arthritis (RA) is an autoimmune disease characterized by infiltration of immune cells in the synovium. However, the crosstalk of immune cells and synovial fibroblasts is still largely ...unknown. Here, global miRNA screening in plasma exosomes was carried out with a custom microarray (RA patients vs. healthy controls = 9:9). A total of 14 exosomal miRNAs were abnormally expressed in the RA patients. Then, downregulated expression of exosomal miR-204-5p was confirmed in both the replication (RA patients vs. healthy controls = 30:30) and validation groups (RA patients vs. healthy controls = 56:60). Similar to the findings obtained in humans, a decreased abundance of exosomal miR-204-5p was observed in mice with collagen-induced arthritis (CIA). Furthermore, Spearman correlation analysis indicated that plasma exosomal miR-204-5p expression was inversely correlated with disease parameters of RA patients, such as rheumatoid factor, erythrocyte sedimentation rate, and C-reactive protein. In vitro, our data showed that human T lymphocytes released exosomes containing large amounts of miR-204-5p, which can be transferred into synovial fibroblasts, inhibiting cell proliferation. Overexpression of miR-204-5p in synovial fibroblasts suppressed synovial fibroblast activation by targeting genes related to cell proliferation and invasion. In vivo assays found that administration of lentiviruses expressing miR-204-5p markedly alleviated the disease progression of the mice with CIA. Collectively, this study identified a novel RA-associated plasma exosomal miRNA-204-5p that mediates the communication between immune cells and synovial fibroblasts and can be used as a potential biomarker for RA diagnosis and treatment.
To identify novel DNA methylation sites significant for rheumatoid arthritis (RA) and comprehensively understand their underlying pathological mechanism.
We performed (1) genome-wide DNA methylation ...and mRNA expression profiling in peripheral blood mononuclear cells from RA patients and health controls; (2) correlation analysis and causal inference tests for DNA methylation and mRNA expression data; (3) differential methylation genes regulatory network construction; (4) validation tests of 10 differential methylation positions (DMPs) of interest and corresponding gene expressions; (5) correlation between
methylation and its mRNA expression level in Jurkat cells and T cells from patients with RA; (6) testing the pathological functions of
in Jurkat cells.
A total of 1046 DNA methylation positions were associated with RA. The identified DMPs have regulatory effects on mRNA expressions. Causal inference tests identified six DNA methylation-mRNA-RA regulatory chains (eg, cg00959259-PARP9-RA). The identified DMPs and genes formed an interferon-inducible gene interaction network (eg,
,
,
and
). Key DMPs and corresponding genes were validated their differences in additional samples. Methylation of PARP9 was correlated with mRNA level in Jurkat cells and T lymphocytes isolated from patients with RA. The
gene exerted significant effects on Jurkat cells (eg, cell cycle, cell proliferation, cell activation and expression of inflammatory factor IL-2).
This multistage study identified an interferon-inducible gene interaction network associated with RA and highlighted the importance of
gene in RA pathogenesis. The results enhanced our understanding of the important role of DNA methylation in pathology of RA.
Prolonged heart rate-corrected QT(QTc) interval is related to ventricular arrhythmia and cardiovascular mortality, with considerably high prevalence of type 2 diabetes. Additionally, long-term ...glycaemic variability could be a significant risk factor for diabetic complications in addition to chronic hyperglycaemia. We compared the associations of long-term glycaemic variability versus sustained chronic hyperglycaemia with the QTc interval among type 2 diabetes patients.
In this cross-sectional study, 2904 type 2 diabetes patients were recruited who had undergone at least four fasting plasma glucose (FPG) and 2-hour postprandial plasma glucose (PPG) measurements (at least once for every 3 months, respectively) during the preceding year. Long-term glycaemic variabilities of FPG and 2-hour PPG were assessed by their standard deviations (SD-FPG and SD-PPG, respectively), and chronic fasting and postprandial hyperglycaemia were assessed by their means (M-FPG and M-PPG, respectively). HbA1c was also determined upon enrolment to assess current overall glycaemic control. QTc interval was estimated from resting 12-lead electrocardiograms, and more than 440 ms was considered abnormally prolonged.
Patients with prolonged QTc interval (≥440 ms) had greater M-FPG, M-PPG, SD-PPG and HbA1c than those with normal QTc interval but comparable SD-FPG. QTc interval was correlated with M-FPG, M-PPG, SD-PPG and HbA1c (r = 0.133, 0.153, 0.245 and 0.207, respectively, p = 0.000) but not with SD-FPG (r = 0.024, p = 0.189). After adjusting for metabolic risk factors via multiple linear regression analysis, SD-PPG, M-PPG and HbA1c (t = 12.16, 2.69 and 10.16, respectively, p = 0.000) were the major independent contributors to the increased QTc interval. The proportion of prolonged QTc interval increased significantly from 10.9% to 14.2% to 26.6% for the first (T1) to second (T2) to third (T3) tertiles of SD-PPG. After adjusting via multiple logistic regression analysis, the odd ratios of prolonged QTc interval of the T2 and T3 versus the T1 of SD-PPG were 1.15 (95% CI, 0.82-1.60) and 2.62 (1.92-3.57), respectively.
Increased long-term variability of PPG is a strong independent risk factor for prolonged QTc interval in type 2 diabetes patients, in addition to long-term postprandial hyperglycaemia and current HbA1c.
This study aims to examine the expression of p53, p16, and murine double minute 2 (MDM2) protein in normal endometrium and endometriosis, in order to discuss the role of p53, p16, and MDM2 protein ...and apoptosis in the pathogenesis and development of endometriosis, and provide a theoretical basis for clinical diagnosis and treatment.The immunohistochemical streptavidin-biotin peroxidase method was used to detect the expression of p53, p16, and MDM2 in tissue samples obtained from 30 women with pathologically confirmed ovarian endometriosis and 29 women with pathologically confirmed normal endometrium. The relationship between p53, p16, and MDM2 expression and apoptosis was analyzed.In normal endometrium, the positive rate of p53 in the secretory phase was higher than that in the proliferative phase (P < .05). Furthermore, the positive rate of p53 in normal endometrium was higher than that in ovarian endometriosis (P < .05). There was a significant difference between normal endometrium and ovarian endometriosis.The positive rate of p16 in normal endometrium was higher than that in ovarian endometriosis (P < .05). Furthermore, there was a significant difference between normal endometrium and ovarian endometriosis. The positive rate of MDM2 in normal endometrium was lower than that in ovarian endometriosis (P < .05).In ovarian endometriosis, the expression of p53 and p16 was positively correlated with each other (r = 0.611, P < .01). However, the expression of p53 and MDM2 was negatively correlated with each other (r = -0.541, P < .01). Furthermore, the expression of p16 and MDM2 might not be relevant in the endometriosis (r = 0.404, P > .05).As important apoptosis regulatory genes, p53, p16, and MDM2 might be involved in the pathogenesis and development of endometriosis.
The medial prefrontal cortex (mPFC) is essential for social behaviors, yet whether and how it encodes social memory remains unclear.
We combined whole-cell patch recording, morphological analysis, ...optogenetic/chemogenetic manipulation, and the TRAP (targeted recombination in active populations) transgenic mouse tool to study the social-associated neural populations in the mPFC.
Fos-TRAPed prefrontal social-associated neurons are excitatory pyramidal neurons with relatively small soma sizes and thin-tufted apical dendrite. These cells exhibit intrinsic firing features of dopamine D1 receptor–like neurons, show persisting firing pattern after social investigation, and project dense axons to nucleus accumbens. In behaving TRAP mice, selective inhibition of prefrontal social-associated neurons does not affect social investigation but does impair subsequent social recognition, whereas optogenetic reactivation of their projections to the nucleus accumbens enables recall of a previously encountered but “forgotten” mouse. Moreover, chemogenetic activation of mPFC-to-nucleus accumbens projections ameliorates MK-801–induced social memory impairments.
Our results characterize the electrophysiological and morphological features of social-associated neurons in the mPFC and indicate that these Fos-labeled, social-activated prefrontal neurons are necessary and sufficient for social memory.
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