Detection of characteristic sub pathway network for angiogenesis based on the comprehensive pathway network

<p>Abstract</p> <p>Background</p> <p>Pathways in biological system often cooperate with each other to function. Changes of interactions among pathways tightly associate with alterations in the properties and functions of the cell and hence alterations in the phenotype. So, the pathway interactions and especially their changes over time corresponding to specific phenotype are critical to understanding cell functions and phenotypic plasticity.</p> <p>Methods</p> <p>With prior-defined pathways and incorporated protein-protein interaction (PPI) data, we counted PPIs between corresponding gene sets of each pair of distinct pathways to construct a comprehensive pathway network. Then we proposed a novel concept, characteristic sub pathway network (CSPN), to realize the phenotype-specific pathway interactions. By adding gene expression data regarding a given phenotype, angiogenesis, active PPIs corresponding to stimulation of interleukin-1 (IL-1) and tumor necrosis factor α (TNF-α) on human umbilical vein endothelial cells (HUVECs) respectively were derived. Two kinds of CSPN, namely the static or the dynamic CSPN, were detected by counting active PPIs.</p> <p>Results</p> <p>A comprehensive pathway network containing 37 signalling pathways as nodes and 263 pathway interactions were obtained. Two phenotype-specific CSPNs for angiogenesis, corresponding to stimulation of IL-1 and TNF-α on HUVEC respectively, were addressed. From phenotype-specific CSPNs, a static CSPN involving interactions among B cell receptor, T cell receptor, Toll-like receptor, MAPK, VEGF, and ErbB signalling pathways, and a dynamic CSPN involving interactions among TGF-β, Wnt, p53 signalling pathways and cell cycle pathway, were detected for angiogenesis on HUVEC after stimulation of IL-1 and TNF-α respectively. We inferred that, in certain case, the static CSPN maintains related basic functions of the cells, whereas the dynamic CSPN manifests the cells' plastic responses to stimulus and therefore reflects the cells' phenotypic plasticity.</p> <p>Conclusion</p> <p>The comprehensive pathway network helps us realize the cooperative behaviours among pathways. Moreover, two kinds of potential CSPNs found in this work, the static CSPN and the dynamic CSPN, are helpful to deeply understand the specific function of HUVEC and its phenotypic plasticity in regard to angiogenesis.</p

Traveling wave solutions and numerical solutions for a mBBM equation

In this paper, some exact meromorphic solutions and generalized trigonometric solutions of the space-time fractional modified Benjamin-Bona-Mahony (mBBM) equation are established by a new transformation and reliable methods. Moreover, some numerical solutions are obtained by using the optimal decomposition method (ODM), and their accuracy is shown in tables and images

Value distribution of q-difference polynomials

In this paper, we deal with the zero distribution of q-difference polynomials  and , where P(f) is a nonzero polynomial of degree l,  is a constant,  and a(z) is a small function of  f

Pro-Angiogenic Role of LncRNA HULC in Microvascular Endothelial Cells via Sequestrating miR-124

Background/Aims: HULC is a multifunctional lncRNA that has pro-angiogenic function in various cancers. The present study was designed to see the role of lncRNA HULC in normal endothelial cells angiogenesis. Methods: Cell viability, apoptosis, migration, tube formation and expression levels of angiogenesis-related proteins were respectively assessed in human microvascular endothelial HMEC-1 cells after lncRNA HULC was silenced by shRNA transfection. Cross-regulation between lncRNA HULC and miR-124, and between miR-124 and MCL-1 were detected by qRT-PCR, sequence analysis, and luciferase reporter assay. Results: Silence of lncRNA HULC significantly reduced viability, migration, tube formation and protein levels of VEGF, VEGFR2, CD144 and eNOS in HMEC-1 cells. Meanwhile, silence of lncRNA HULC induced apoptosis in HMEC-1 cells, as Bcl-2 was down-regulated, Bax was up-regulated, and caspase-3 and -9 were cleaved. miR-124 expression was negatively regulated by lncRNA HULC, and HULC worked as a molecular sponge for miR-124, in having miR-124 exhausted. Besides, MCL-1 was a target gene of miR-124. Rescue assay results showed that the effects of lncRNA HULC silence on HMEC-1 cells growth, migration and angiogenesis were abolished by miR-124 suppression. Similarly, the effects of miR-124 on HMEC-1 cells were abolished by MCL-1 overexpression. Furthermore, MCL-1 activated PI3K/AKT and JAK/STAT signaling pathways. Conclusion: These findings suggest a pro-angiogenic role of lncRNA HULC in endothelial cells. The pro-angiogenic actions of lncRNA HULC may be through sponging miR-124, preventing MCL-1 from degradation by miR-124

The complex interplay of hypoxia and sleep disturbance in gray matter structure alterations in obstructive sleep apnea patients

BackgroundObstructive Sleep Apnea (OSA) characteristically leads to nocturnal hypoxia and sleep disturbance. Despite clear evidence of OSA-induced cognitive impairments, the literature offers no consensus on the relationship between these pathophysiological processes and brain structure alterations in patients.ObjectiveThis study leverages the robust technique of structural equation modeling to investigate how hypoxia and sleep disturbance exert differential effects on gray matter structures.MethodsSeventy-four Male participants were recruited to undergo overnight polysomnography and T1-weighted Magnetic Resonance Imaging. Four structural outcome parameters were extracted, namely, gray matter volume, cortical thickness, sulcal depth, and fractal dimension. Structural equation models were constructed with two latent variables (hypoxia, and sleep disturbance) and three covariates (age, body mass index, and education) to examine the association between gray matter structural changes in OSA and the two latent variables, hypoxia and sleep disturbance.ResultsThe structural equation models revealed hypoxia-associated changes in diverse regions, most significantly in increased gray matter volume, cortical thickness and sulcal depth. In contrast, sleep disturbance. Was shown to be largely associated with reduce gray matter volume and sulcal depth.ConclusionThis study provides new evidence showing significant effects of OSA-induced hypoxia and sleep disturbance on gray matter volume and morphology in male patients with obstructive sleep apnea. It also demonstrates the utility of robust structural equation models in examining obstructive sleep apnea pathophysiology

Is Increasing Diet Diversity of Animal-Source Foods Related to Better Health-Related Quality of Life among Chinese Men and Women?

Diet plays a crucial role in regulating individuals’ lifestyles and is closely related to health. The intake of animal-sourced foods (ASF) provides the human body with high-quality protein and various micronutrients. This study aimed to investigate whether the diversity of animal foods has a positive impact on the health-related quality of life (HRQoL) among residents. The data came from the Shaanxi baseline survey of the Northwest Chinese Regional Ethnic Cohort Study, which recruited more than 100 thousand participants aged 35 to 74 from five provinces between June 2018 and May 2019. A total of 39,997 participants in Shaanxi (mean age: 50 years; 64% women) were finally included in this current study. The animal source food diet diversity score (ASFDDS) was established based on the frequency of consuming pork, mutton, beef, poultry, seafood, eggs, pure milk, and yogurt. The physical component score (PCS) and mental component score (MCS), ranging from 0 to 100 on the 12-Item Short Form Survey (SF-12), were used to assess participants’ HRQoL. Better PCS/MCS was defined as scores higher than the 90th percentile. The results showed that men had a higher intake of ASF and ASFDDS than women. After adjusting for potential confounders, compared with those who never or rarely consumed animal foods, the likelihood of having better PCS and MCS increased by 16% (OR = 1.16, 95%CI: 1.01–1.34) and 24% (OR = 1.24, 95%CI: 1.03–1.448), respectively, in men with an ASFDDS ≥ 2. In women, a 34% increase (OR = l.34, 95%CI: 116–l.54) likelihood for better PCS was observed for an ASFDDS ≥ 2, but no association was observed for MCS. Increasing each specific animal source’s food intake was associated with better PCS after adjusting for all covariates. However, for MCS, positive associations were only observed in seafood consumption among men and eggs among women. Restricted cubic splines showed a substantial dose-response association between intake frequency of animal-source foods and PCS, both in men and women. The study suggests that a diverse intake of animal-sourced foods can potentially improve the HRQoL of Chinese adults