Catalogue Search | MBRL
Are you sure you want to remove the book from the shelf?
{{itemTitle}}
20,185
result(s) for
"Cheng, Liang"
Sort by:
Mitochondrial oxidative stress in the tumor microenvironment and cancer immunoescape: foe or friend?
The major concept of \"oxidative stress\" is an excess elevated level of reactive oxygen species (ROS) which are generated from vigorous metabolism and consumption of oxygen. The precise harmonization of oxidative stresses between mitochondria and other organelles in the cell is absolutely vital to cell survival. Under oxidative stress, ROS produced from mitochondria and are the major mediator for tumorigenesis in different aspects, such as proliferation, migration/invasion, angiogenesis, inflammation, and immunoescape to allow cancer cells to adapt to the rigorous environment. Accordingly, the dynamic balance of oxidative stresses not only orchestrate complex cell signaling events in cancer cells but also affect other components in the tumor microenvironment (TME). Immune cells, such as M2 macrophages, dendritic cells, and T cells are the major components of the immunosuppressive TME from the ROS-induced inflammation. Based on this notion, numerous strategies to mitigate oxidative stresses in tumors have been tested for cancer prevention or therapies; however, these manipulations are devised from different sources and mechanisms without established effectiveness. Herein, we integrate current progress regarding the impact of mitochondrial ROS in the TME, not only in cancer cells but also in immune cells, and discuss the combination of emerging ROS-modulating strategies with immunotherapies to achieve antitumor effects.
Journal Article
The gale
\"One morning, so early that the fog still clings to the surface of the river, a young boy accompanies his yeye seven miles to the grassy field behind their home in order to cut satintail to feed the livestock.-- Provided by publisher.
CHILDBOOK
Translation of the circular RNA circβ-catenin promotes liver cancer cell growth through activation of the Wnt pathway
Background
Circular RNAs are a class of regulatory RNA transcripts, which are ubiquitously expressed in eukaryotes. In the current study, we evaluate the function of a novel circRNA derived from the β-catenin gene locus, circβ-catenin.
Results
Circβ-catenin is predominantly localized in the cytoplasm and displays resistance to RNase-R treatment. We find that circβ-catenin is highly expressed in liver cancer tissues when compared to adjacent normal tissues. Silencing of circβ-catenin significantly suppresses malignant phenotypes in vitro and in vivo, and knockdown of this circRNA reduces the protein level of β-catenin without affecting its mRNA level. We show that circβ-catenin affects a wide spectrum of Wnt pathway-related genes, and furthermore, circβ-catenin produces a novel 370-amino acid β-catenin isoform that uses the start codon as the linear β-catenin mRNA transcript and translation is terminated at a new stop codon created by circularization. We find that this novel isoform can stabilize full-length β-catenin by antagonizing GSK3β-induced β-catenin phosphorylation and degradation, leading to activation of the Wnt pathway.
Conclusions
Our findings illustrate a non-canonical function of circRNA in modulating liver cancer cell growth through the Wnt pathway, which can provide novel mechanistic insights into the underlying mechanisms of hepatocellular carcinoma.
Journal Article
Laplace approximation, penalized quasi-likelihood, and adaptive Gauss–Hermite quadrature for generalized linear mixed models: towards meta-analysis of binary outcome with sparse data
Background
In meta-analyses of a binary outcome, double zero events in some studies cause a critical methodology problem. The generalized linear mixed model (GLMM) has been proposed as a valid statistical tool for pooling such data. Three parameter estimation methods, including the Laplace approximation (LA), penalized quasi-likelihood (PQL) and adaptive Gauss–Hermite quadrature (AGHQ) were frequently used in the GLMM. However, the performance of GLMM via these estimation methods is unclear in meta-analysis with zero events.
Methods
A simulation study was conducted to compare the performance. We fitted five random-effects GLMMs and estimated the results through the LA, PQL and AGHQ methods, respectively. Each scenario conducted 20,000 simulation iterations. The data from Cochrane Database of Systematic Reviews were collected to form the simulation settings. The estimation methods were compared in terms of the convergence rate, bias, mean square error, and coverage probability.
Results
Our results suggested that when the total events were insufficient in either of the arms, the GLMMs did not show good point estimation to pool studies of rare events. The AGHQ method did not show better properties than the LA estimation in terms of convergence rate, bias, coverage, and possibility to produce very large odds ratios. In addition, although the PQL had some advantages, it was not the preferred option due to its low convergence rate in some situations, and the suboptimal point and variance estimation compared to the LA.
Conclusion
The GLMM is an alternative for meta-analysis of rare events and is especially useful in the presence of zero-events studies, while at least 10 total events in both arms is recommended when employing GLMM for meta-analysis. The penalized quasi-likelihood and adaptive Gauss–Hermite quadrature are not superior to the Laplace approximation for rare events and thus they are not recommended.
Journal Article
Study of Advective Energy Transport in the Inflow and Outflow of Super-Eddington Accretion Flows
Photon trapping is believed to be an important mechanism in super-Eddington accretion, which greatly reduces the radiative efficiency as photons are swallowed by the central black hole before they can escape from the accretion flow. This effect is interpreted as the radial advection of energy in one-dimensional height-integrated models, such as the slim-disk model. However, when multidimensional effects are considered, the conventional understanding may no longer hold. In this paper, we study the advective energy transport in super-Eddington accretion based on a new two-dimensional inflow–outflow solution with radial self-similarity, in which the advective factor is calculated self-consistently by incorporating the calculation of radiative flux instead of being set as an input parameter. We found that radial advection is actually a heating mechanism in the inflow due to compression, and the energy balance in the inflow is maintained by cooling via radiation and vertical (θ-direction) advection, which transports entropy upward to be radiated closer to the surface or carried away by the outflow. As a result, fewer photons are advected inward, and more photons are released from the surface, so that the mean advective factor is smaller and the emergent flux is higher than the fluxes predicted by the slim-disk model. The radiative efficiency of super-Eddington accretion thus should be higher than that of the slim-disk model, which agrees with the results of some recent numerical simulations.
Journal Article
Mitochondrial Lon-induced mtDNA leakage contributes to PD-L1–mediated immunoescape via STING-IFN signaling and extracellular vesicles
BackgroundMitochondrial Lon is a chaperone and DNA-binding protein that functions in protein quality control and stress response pathways. The level of Lon regulates mitochondrial DNA (mtDNA) metabolism and the production of mitochondrial reactive oxygen species (ROS). However, there is little information in detail on how mitochondrial Lon regulates ROS-dependent cancer immunoescape through mtDNA metabolism in the tumor microenvironment (TME).MethodsWe explored the understanding of the intricate interplay between mitochondria and the innate immune response in the inflammatory TME.ResultsWe found that oxidized mtDNA is released into the cytosol when Lon is overexpressed and then it induces interferon (IFN) signaling via cGAS-STING-TBK1, which upregulates PD-L1 and IDO-1 expression to inhibit T-cell activation. Unexpectedly, upregulation of Lon also induces the secretion of extracellular vehicles (EVs), which carry mtDNA and PD-L1. Lon-induced EVs further induce the production of IFN and IL-6 from macrophages, which attenuates T-cell immunity in the TME.ConclusionsThe levels of mtDNA and PD-L1 in EVs in patients with oral cancer function as a potential diagnostic biomarker for anti-PD-L1 immunotherapy. Our studies provide an insight into the immunosuppression on mitochondrial stress and suggest a therapeutic synergy between anti-inflammation therapy and immunotherapy in cancer.
Journal Article
Adaptive multi-view multi-label learning for identifying disease-associated candidate miRNAs
Increasing evidence has indicated that microRNAs(miRNAs) play vital roles in various pathological processes and thus are closely related with many complex human diseases. The identification of potential disease-related miRNAs offers new opportunities to understand disease etiology and pathogenesis. Although there have been numerous computational methods proposed to predict reliable miRNA-disease associations, they suffer from various limitations that affect the prediction accuracy and their applicability. In this study, we develop a novel method to discover disease-related candidate miRNAs based on Adaptive Multi-View Multi-Label learning(AMVML). Specifically, considering the inherent noise existed in the current dataset, we propose to learn a new affinity graph adaptively for both diseases and miRNAs from multiple similarity profiles. We then simultaneously update the miRNA-disease association predicted from both spaces based on multi-label learning. In particular, we prove the convergence of AMVML theoretically and the corresponding analysis indicates that it has a fast convergence rate. To comprehensively illustrate the prediction performance of our method, we compared AMVML with four state-of-the-art methods under different validation frameworks. As a result, our method achieves comparable performance under various evaluation metrics, which suggests that our method is capable of discovering greater number of true miRNA-disease associations. The case study conducted on thyroid neoplasms further identified a potential diagnostic biomarker. Together, the experimental results confirms the utility of our method and we anticipate that our method could serve as a reliable and efficient tool for uncovering novel disease-related miRNAs.
Journal Article