Background and Purpose
Mitochondrial damage and oxidative stress are crucial contributors to the tubular cell injury and death in acute kidney injury. Novel therapeutic strategies targeting ...mitochondria protection and halting the progression of acute kidney injury are urgently needed. Honokiol is a small‐molecule polyphenol that exhibits extraordinary cytoprotective effects, such as anti‐inflammatory and anti‐oxidative. Thus, we investigated whether honokiol could ameliorate cisplatin‐induced acute kidney injury via preventing mitochondrial dysfunction.
Experimental Approach
Acute kidney injury was induced by cisplatin administration. Biochemical and histological analysis were used to determine kidney injury. The effect of honokiol on mitochondrial function and morphology were determined using immunohistochemistry, transmission electron microscopy, immunoblot and immunofluorescence. To investigate the mechanism by which honokiol alters mitochondrial dynamics, remodelling and resistance to apoptosis, we used transfection experiments, immunoblotting, immunoprecipitation and flow cytometry assay.
Key Results
We demonstrated that the prominent mitochondrial fragmentation occurred in experimental models of cisplatin‐induced nephrotoxicity, which was coupled to radical oxygen species (ROS) overproduction, deterioration of mitochondrial function, release of apoptogenic factors and the consequent apoptosis. Honokiol treatment caused notable reno‐protection and attenuated of these cisplatin‐induced changes. Mechanistically, honokiol treatment recovered the expression of SIRT3 and improved AMPK activity in tubular cells exposure to cisplatin, which preserved the Drp1 phosphorylation at Ser637 and blocked its translocation in mitochondria, consequently preventing mitochondrial fragmentation and subsequent cell injury and death.
Conclusion and Implications
Our results indicate that honokiol may protect against cisplatin‐induced acute kidney injury by preserving mitochondrial integrity and function by SIRT3/AMPK‐dependent mitochondrial dynamics remodelling.
Long non-coding RNAs (LncRNAs) have been demonstrated to play crucial role in tumor growth and metastasis for hepatocellular carcinoma (HCC). LncRNA FAL1 has been indicated to promote the progression ...of various cancers. However, the role of lncRNA FAL1 in HCC was poorly understood.
The expression levels of lncRNA FAL1 in HCC tissues and cells were determined by RT-qPCR. The roles of lncRNA FAL1 on HCC cells were investigated by MTT, colony formation, transwell, RT-qPCR, and Western blotting. The miRNA binding sites of lncRNA FAL1 was predicted using RegRNA 2.0 and miR-1236 was validated to target lncRNA FAL1 by luciferase reporter assays and RT-qPCR. Finally, the expression levels of lncRNA FAL1 in serum exosome of HCC patients was also investigated and the role of exosome-mediated lncRNA FAL1 was further investigated by co-culturing with HCC cells.
This study first showed that lncRNA FAL1 was up-regulated in HCC tissues and functioned as an oncogene in HCC. LncRNA FAL1 could accelerate cell proliferation and metastasis as a ceRNA mechanism by competitively binding to miR-1236. Moreover, lncRNA FAL1 was also up-regulated in serum exosome of HCC patients and could transfer lncRNA FAL1 to HCC cells to increase their abilities of cell proliferation and migration.
Taken together, this study indicated that lncRNA FAL1 functions as an oncogenic in HCC and may be a novel diagnostic biomarker or a novel target for the treatment of HCC in future.
Efficient Core Maintenance in Large Dynamic Graphs Rong-Hua Li; Yu, Jeffrey Xu; Rui Mao
IEEE transactions on knowledge and data engineering,
2014-Oct., 2014-10-00, 20141001, Volume:
26, Issue:
10
Journal Article
Peer reviewed
Open access
The k-core decomposition in a graph is a fundamental problem for social network analysis. The problem of k-core decomposition is to calculate the core number for every node in a graph. Previous ...studies mainly focus on k-core decomposition in a static graph. There exists a linear time algorithm for k-core decomposition in a static graph. However, in many real-world applications such as online social networks and the Internet, the graph typically evolves overtime. In such applications, a key issue is to maintain the core numbers of nodes when the graph changes overtime. A simple implementation is to perform the linear time algorithm to recompute the core number for every node after the graph is updated. Such simple implementation is expensive when the graph is very large. In this paper, we propose a new efficient algorithm to maintain the core number for every node in a dynamic graph. Our main result is that only certain nodes need to update their core numbers when the graph is changed by inserting/deleting an edge. We devise an efficient algorithm to identify and recompute the core numbers of such nodes. The complexity of our algorithm is independent of the graph size. In addition, to further accelerate the algorithm, we develop two pruning strategies by exploiting the lower and upper bounds of the core number. Finally, we conduct extensive experiments over both real-world and synthetic datasets, and the results demonstrate the efficiency of the proposed algorithm.
Here, we report the first example of Ni‐catalyzed asymmetric hydrosilylation of 1,1‐disubstituted allenes with high level of regioselectivities and enantioselectivities. The key to achieve this ...stereoselective hydrosilylation reaction was the development of the SPSiOL‐derived bisphosphite ligands (SPSiPO). This protocol features broad substrate scope, excellent functional group, and heterocycle tolerance, thus provides a versatile method for the construction of enantioenriched tertiary allylsilanes in a straightforward and atom‐economic manner. DFT calculations were performed to reveal the reaction mechanism and the origins of the enantioselectivity.
With a newly developed SPSiOL‐base bisphosphite ligand (SPSiPO), Ni‐catalyzed asymmetric hydrosilylation of 1,1‐disubstituted allenes was realized for the first time, delivering the enantioenriched allylsilanes bearing a tertiary carbon stereocenter in high efficiency and 100 % atom‐economy with high chemo‐, regio‐ and enantioselectivities.
With the development over the past decades, mobile edge computing has been widely used in many fields. Benefit from the low latency brought by the proximity of mobile edge computing to the user side ...and the relief of bandwidth pressure, mobile edge computing can play a significant role in services with large backhaul traffic such as live video streaming. However, the edge server does not have the same powerful hardware as the cloud server, and the limited resources on the edge server make the deployment of services need to be carefully considered. Small-sized service providers in edge networks may not have their own edge servers and need to rent the edge servers of edge server providers to deploy their own services. In this paper, we present a service provider profit maximization problem under the service scenario of large backhaul traffic. Considering the needs of server providers and service providers, we design a novel method, Distributed Profit-based Matching Algorithm (DPMA), to solve this problem according to the idea of Deferred Acceptance algorithm. The experimental results show that the proposed method is superior to the existing profit maximization methods in mobile edge computing.
The long noncoding RNA (lncRNA)
has previously been identified as a prognostic marker in hepatocellular carcinoma. Here, we performed a comprehensive analysis of lncRNA expression profiles from ...RNA-Seq data and report that
plays a similar role in lung cancer. Analysis of 918 lung cancer and normal lung tissues and lung cancer cell lines revealed that
was significantly downregulated in lung cancer; this decreased expression was associated with poor patient survival.
bound and stabilized the YBX1 protein. Silencing of
triggered both cell survival and cell death signaling through dysregulation of the oncogenes YBX1, MET, and p21. In this
network, p21 played an oncogenic role by promoting cell proliferation and antiapoptosis in lung cancers.
played a tumor-suppressive role as indicated by inhibition of multiple cell cycle-related genes in human primary lung tumors. These data show that
has potential as a new diagnostic and prognostic marker and as a therapeutic target for lung cancer.
The lncRNA
functions as a tumor suppressor, with potential use a diagnostic/prognostic marker and therapeutic target in lung cancer.
.
The overall efficacy of chimeric antigen receptor modified T cells (CARTs) remain limited in solid tumors despite intensive studies that aim at targeting multiple antigens, enhancing migration, ...reducing tonic signaling, and improving tumor microenvironment. On the other hand, how the affinity and engaging kinetics of antigen-binding domain (ABD) affects the CART’s efficacy has not been carefully investigated. In this article, we first analyzed 38 published solid tumor CART trials and correlated the response rate to their ABD affinity. Not surprisingly, majority (25 trials) of the CARTs utilized high-affinity ABDs, but generated merely 5.7% response rate. In contrast, 35% of the patients treated with the CARTs built from moderate-affinity ABDs had clinical responses. Thus, CARTs with moderate-affinity ABDs not only have less off-target toxicity, but also are more effective. We then reviewed the effects of ABD affinity on the biology and function of CARTs, providing further evidence that moderate-affinity ABDs may be better in CART development. In the end, we propose that a fast-on/fast-off (high
K
on
and
K
off
) kinetics of CART-target engagement in solid tumor allow CARTs to generate sufficient signaling to kill tumor cells without being driven to exhaustion. We believe that studying the ABD affinity and the kinetics of CART-tumor interaction may hold a key to designing effective CARTs for solid tumors.
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