38 research outputs found
Knock-down of glutaminase 2 expression decreases glutathione, NADH, and sensitizes cervical cancer to ionizing radiation
AbstractPhosphate-activated mitochondrial glutaminase (GLS2) is suggested to be linked with elevated glutamine metabolism. It plays an important role in catalyzing the hydrolysis of glutamine to glutamate. The present study was to investigate the potent effect of GLS2 on radioresistance of cervical carcinoma. GLS2 was examined in 144 cases of human cervical cancer specimens (58 radioresistant specimens, 86 radiosensitive specimens) and 15 adjacent normal cervical specimens with immunohistochemistry. HeLa cells were treated with a cumulative dose of 50Gy X-rays, over 6months, yielding the resistant sub-line HeLaR. The expressions of GLS2 were measured by Western blot. Radioresistance was tested by colony survival assay. Apoptosis was determined by flow cytometry. The levels of glutathione (GSH), reactive oxygen species (ROS), NAD+/NADH ratio and NADP+/NADPH ratio were detected by quantization assay kit. Xenografts were used to confirm the effect of GLS2 on radioresistance in vivo. The expressions of GLS2 were significantly enhanced in tumor tissues of radioresistant patients compared with that in radiosensitive patients. In vitro, the radioresistant cell line HeLaR exhibited significantly increased GLS2 levels than its parental cell line HeLa. GLS2 silenced radioresistant cell HeLaR shows substantially enhanced radiosensitivity with lower colony survival and higher apoptosis in response to radiation. In vivo, xenografts with GLS2 silenced HeLaR were more sensitive to radiation. At the molecular level, knock-down of GLS2 increased the intracellular ROS levels of HeLaR exposed to irradiation by decreasing the productions of antioxidant GSH, NADH and NADPH. GLS2 may have an important role in radioresistance in cervical cancer patients
Leptin promotes epithelial-mesenchymal transition of breast cancer via the upregulation of pyruvate kinase M2
Mechanism of ice nucleation inhibition of PVA and PVP in aqueous glycerin solution
In order to find effective anti-ice nucleation agents, polyvinyl pyrrolidone
(PVP) and polyvinyl alcohol (PVA) as additives in glycerin â water solution was froze
and investigated by Differential Scanning Calorimeter (DSC). The results show that
PVA has stronger inhibition effect than PVP, and the effect can be enhanced with
increasing of the additive concentration. The solution nucleation temperature was found
to be 216.61 K at PVA concentration of 3 wt%. Radial distribution function (RDF) was
established by molecular dynamics simulation to find that PVA molecule forms stronger
and more stable hydrogen bonds with water molecules than PVP. Therefore, the PVA
performs better in decreasing nucleation temperature than PVP. For PVA concentration
of 3 wt%, the phase transition temperature was predicted to be 213.15 K-218.15 K
based on the value of mean squared displacement (MSD). This is in close agreement
with the experimental results
Disturbing cytoskeleton by engineered nanomaterials for enhanced cancer therapeutics
Cytoskeleton plays a significant role in the shape change, migration, movement, adhesion, cytokinesis, and phagocytosis of tumor cells. In clinical practice, some anti-cancer drugs achieve cytoskeletal therapeutic effects by acting on different cytoskeletal protein components. However, in the absence of cell-specific targeting, unnecessary cytoskeletal recombination in organisms would be disastrous, which would also bring about severe side effects during anticancer process. Nanomedicine have been proven to be superior to some small molecule drugs in cancer treatment due to better stability and targeting, and lower side effects. Therefore, this review summarized the recent developments of various nanomaterials disturbing cytoskeleton for enhanced cancer therapeutics, including carbon, noble metals, metal oxides, black phosphorus, calcium, silicon, polymers, peptides, and metal-organic frameworks, etc. A comprehensive analysis of the characteristics of cytoskeleton therapy as well as the future prospects and challenges towards clinical application were also discussed. We aim to drive on this emerging topic through refreshing perspectives based on our own work and what we have also learnt from others. This review will help researchers quickly understand relevant cytoskeletal therapeutic information to further advance the development of cancer nanomedicine
Leptin promotes epithelial-mesenchymal transition of breast cancer via the upregulation of pyruvate kinase M2
Abstract Background Accumulating researches have shown that epithelial-mesenchymal transition (EMT) contributes to tumor metastasis. Leptin, a key adipokine secreted from adipocytes, shapes the tumor microenvironment, potentiates the migration of breast cancer cells and angiogenesis, and is also involved in EMT. However, the potential mechanism remains unknown. This study aims to explore the effect of leptin on EMT in breast cancer cells and the underlying mechanism. Methods With the assessment of EMT-associated marker expression in MCF-7, SK-BR-3, and MDA-MB-468 cells, the effect of leptin on breast cancer cells was analyzed. Besides, an array of pathway inhibitors as well as RNA interference targeting pyruvate kinase M2 (PKM2) were used to clarify the underlying mechanism of leptin-mediated EMT in vitro and in vivo. Results The results demonstrated that leptin promoted breast cancer cells EMT, visibly activated the PI3K/AKT signaling pathway, and upregulated PKM2 expression. An antibody against the leptin receptor (anti-ObR) and the PI3K/AKT signaling pathway inhibitor LY294002 significantly abolished leptin-induced PKM2 expression and EMT-associated marker expression. SiRNA targeting PKM2 partially abolished leptin-induced migration, invasion, and EMT-associated marker expression. In vivo xenograft experiments indicated that RNA interference against PKM2 suppressed breast cancer growth and metastasis. Conclusions Our data suggest that leptin promotes EMT in breast cancer cells via the upregulation of PKM2 expression as well as activation of PI3K/AKT signaling pathway, and PKM2 might be one of the key points and potential targets for breast cancer therapy
Insights into the major aroma-active compounds in clear red raspberry juice (Rubus idaeus L. cv. Heritage) by molecular sensory science approaches
Preliminary Selection and Analysis of Deltamethrin-Resistant Strains of Aedes albopictus
The synthesis and oligomerization of a monofunctional bottlebrush-shaped polymer terminated with an azide group
High-Density Nanosharp Microstructures Enable Efficient CO<sub>2</sub> Electroreduction
Conversion of CO<sub>2</sub> to CO
powered by renewable electricity not only reduces CO<sub>2</sub> pollution
but also is a means to store renewable energy via chemical production
of fuels from CO. However, the kinetics of this reaction are slow
due its large energetic barrier. We have recently reported CO<sub>2</sub> reduction that is considerably enhanced via local electric
field concentration at the tips of sharp gold nanostructures. The
high local electric field enhances CO<sub>2</sub> concentration at
the catalytic active sites, lowering the activation barrier. Here
we engineer the nucleation and growth of next-generation Au nanostructures.
The electroplating overpotential was manipulated to generate an appreciably
increased density of honed nanoneedles. Using this approach, we report
the first application of sequential electrodeposition to increase
the density of sharp tips in CO<sub>2</sub> electroreduction. Selective
regions of the primary nanoneedles are passivated using a thiol SAM
(self-assembled monolayer), and then growth is concentrated atop the
uncovered high-energy planes, providing new nucleation sites that
ultimately lead to an increase in the density of the nanosharp structures.
The two-step process leads to a new record in CO<sub>2</sub> to CO
reduction, with a geometric current density of 38 mA/cm<sup>2</sup> at â0.4 V (vs reversible hydrogen electrode), and a 15-fold
improvement over the best prior reports of electrochemical surface
area (ECSA) normalized current density