Cytoprotective Activity of Glycyrrhizae radix Extract Against Arsenite-induced Cytotoxicity

Licorice, Glycyrrhizae radix, is one of the herbal medicines in East Asia that has been commonly used for treating various diseases, including stomach disorders. This study investigated the effect of licorice on arsenite (As)-induced cytotoxicity in H4IIE cells, a rat hepatocyte-derived cell line. Cell viability was significantly diminished in As-treated H4IIE cells in a time and concentration-dependent manner. Furthermore, results from flow cytometric assay and DNA laddering in H4IIE cells showed that As treatment induced apoptotic cell death by activating caspase-3. Licorice (0.1 and 1.0 mg ml−1) treatment significantly inhibited cell death and the activity of caspase-3 in response to As exposure. These results demonstrate that licorice induced a cytoprotective effect against As-induced cell death by inhibition of caspase-3

In-rich InGaN/GaN quantum wells grown by metal-organic chemical vapor deposition

Growth mechanism of In-rich InGaN/GaN quantum wells (QWs) was investigated. First, we examined the initial stage of InN growth on GaN template considering strain-relieving mechanisms such as defect generation, islanding, and alloy formation at 730 degrees C. It was found that, instead of formation of InN layer, defective In-rich InGaN layer with thickness fluctuations was formed to relieve large lattice mismatch over 10% between InN and GaN. By introducing growth interruption (GI) before GaN capping at the same temperature, however, atomically flat InGaN/GaN interfaces were observed, and the quality of In-rich InGaN layer was greatly improved. We found that decomposition and mass transport processes during GI in InGaN layer are responsible for this phenomenon. There exists severe decomposition in InGaN layer during GI, and a 1-nm-thick InGaN layer remained after GI due to stronger bond strength near the InGaN/GaN interface. It was observed that the mass transport processes actively occurred during GI in InGaN layer above 730 degrees C so that defect annihilation in InGaN layer was greatly enhanced. Finally, based on these experimental results, we propose the growth mechanism of In-rich InGaN/GaN QWs using GI.open9

The transcriptional activator Gli2 modulates T-cell receptor signalling through attenuation of AP-1 and NFκB activity

Different tissues contain diverse and dynamic cellular niches, providing distinct signals to tissue-resident or migratory infiltrating immune cells. Hedgehog (Hh) proteins are secreted inter-cellular signalling molecules, which are essential during development and are important in cancer, post-natal tissue homeostasis and repair. Hh signalling mediated by the Hh-responsive transcription factor Gli2 also has multiple roles in T-lymphocyte development and differentiation.Here, we investigate the function of Gli2 in T-cell signalling and activation. Gene transcription driven by the Gli2 transcriptional activator isoform (Gli2A) attenuated T-cell activation and proliferation following T-cell receptor (TCR) stimulation. Expression of Gli2A in T-cells altered gene expression profiles, impaired the TCR-induced Ca2+ flux and nuclear expression of NFAT2, suppressed upregulation of molecules essential for activation, and attenuated signalling pathways upstream of the AP-1 and NFκB complexes, leading to reduced activation of these important transcription factors. Inhibition of physiological Hh-dependent transcription increased NFκB activity upon TCR ligation. These data are important for nderstanding the molecular mechanisms of immunomodulation, particularly in tissues where Hh proteins or other Gli-activating ligands such as TGFβ are upregulated, including during inflammation, tissue damage and repair, and in tumour microenvironments

LONP1 and ClpP cooperatively regulate mitochondrial proteostasis for cancer cell survival

Mitochondrial proteases are key components in mitochondrial stress responses that maintain proteostasis and mitochondrial integrity in harsh environmental conditions, which leads to the acquisition of aggressive phenotypes, including chemoresistance and metastasis. However, the molecular mechanisms and exact role of mitochondrial proteases in cancer remain largely unexplored. Here, we identified functional crosstalk between LONP1 and ClpP, which are two mitochondrial matrix proteases that cooperate to attenuate proteotoxic stress and protect mitochondrial functions for cancer cell survival. LONP1 and ClpP genes closely localized on chromosome 19 and were co-expressed at high levels in most human cancers. Depletion of both genes synergistically attenuated cancer cell growth and induced cell death due to impaired mitochondrial functions and increased oxidative stress. Using mitochondrial matrix proteomic analysis with an engineered peroxidase (APEX)-mediated proximity biotinylation method, we identified the specific target substrates of these proteases, which were crucial components of mitochondrial functions, including oxidative phosphorylation, the TCA cycle, and amino acid and lipid metabolism. Furthermore, we found that LONP1 and ClpP shared many substrates, including serine hydroxymethyltransferase 2 (SHMT2). Inhibition of both LONP1 and ClpP additively increased the amount of unfolded SHMT2 protein and enhanced sensitivity to SHMT2 inhibitor, resulting in significantly reduced cell growth and increased cell death under metabolic stress. Additionally, prostate cancer patients with higher LONP1 and ClpP expression exhibited poorer survival. These results suggest that interventions targeting the mitochondrial proteostasis network via LONP1 and ClpP could be potential therapeutic strategies for cancer

Exome and genome sequencing of nasopharynx cancer identifies NF-κB pathway activating mutations

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Risk to human health related to the presence of perfluoroalkyl substances in food

Acknowledgements: The Panel wishes to thank the following for their support provided to this scientific output as Hearing experts: Klaus Abraham, Esben Budtz-Jørgensen, Tony Fletcher, Philippe Grandjean, Hans Mielke and Hans Rumke and EFSA staff members: Davide Arcella, Marco Binaglia, Petra Gergelova, Elena Rovesti and Marijke Schutte. The Panel wishes to acknowledge all European competent institutions, Member State bodies and other organisations that provided data for this scientific output. The Panel would also like to thank the following authors and co-authors for providing additional information in relation to their respective studies: Berit Granum, Margie M Peden-Adams, Thomas Webster.Peer reviewedPublisher PD