Eriodictyol modulates glioma cell autophagy and apoptosis by inhibition of PI3K/Akt/mTOR signaling pathway

Purpose: To investigate the effects of eriodictyol (ERD) on U251 human glioma cell cycle and viability, autophagy and apoptosis by modulation of PI3/Akt/mTOR signaling cascade. Methods: 740 Y-P was used to activate U251 human glioma cells. For exploring ERD effects, the U251 cells were treated with ERD and 740 Y-P together. MTT assay was used to elucidate cell viability and apoptosis. The expression of autophagic proteins (LC3B and Beclin-1), and apoptotic proteins (Bcl-2 and Bax) were quantified using Western blotting. To explore the role of PI3K/Akt/mTOR signaling pathway, their expression was measured in comparison to their respective phosphorylated derivatives by Western blotting. Results: ERD exposure downregulated p-PI3K and p-Akt protein expression. The results also indicate that ERD reduced cell viability and stimulated apoptosis in U251 cells (p < 0.05). Consequently, Bax expression was upregulated and the expression of Bcl-2 was downregulated. ERD enhanced the autophagy of glioma cells U251 by enhancing LC3B and Beclin-1 expression (p < 0.05). These effects were opposite to that revealed by 740 Y-P exposure alone. Conclusion: ERD reduces U251 human glioma cell viability, and triggers cell autophagy and apoptosis, which is significantly correlated to downregulation of PI3K/Akt/mTOR signalling cascade. Thus, the compound can potentially be used for the treatment of glioma

Genetic polymorphisms of TLR3 are associated with Nasopharyngeal carcinoma risk in Cantonese population

<p>Abstract</p> <p>Background</p> <p>Nasopharyngeal carcinoma is endemic in Southern China, displays a strong relationship with genetic susceptibility and associates with Epstein-Barr virus infection. Toll-like receptor 3 (TLR3) plays an important role in the antivirus response. Therefore, we examined the association between <it>TLR3 </it>gene polymorphisms and NPC susceptibility.</p> <p>Methods</p> <p>We performed a case-control study of 434 NPC cases and 512 healthy controls matched on age, sex and residence. Both cases and controls are of Cantonese origin from Southern China. Genetic variants in <it>TLR3 </it>were determined by polymerase chain reaction (PCR)-based DNA direct sequencing and four SNPs were genotyped in all samples.</p> <p>Results</p> <p>Our results showed that allele C for SNP 829A/C increased NPC risk significantly ((p = 0.0068, OR = 1.49, 95%CI:1.10–2.00). When adjusted for age, gender and VCA-IgA antibody titers, the NPC risk was reduced significantly among individuals who carried the haplotype "ATCT" compared to those who carried the most common haplotype "ACCT" (p = 0.0054, OR = 0.028; 95% CI (0.002–0.341).</p> <p>Conclusion</p> <p>The <it>TLR3 </it>polymorphisms may be relevant to NPC susceptibility in the Cantonese population, although the reduction in NPC risk is modest and the biological mechanism of the observed association merits further investigation.</p

Activation of PI3K/AKT and ERK MAPK signal pathways is required for the induction of lytic cycle replication of Kaposi's Sarcoma-associated herpesvirus by herpes simplex virus type 1

<p>Abstract</p> <p>Background</p> <p>Kaposi's sarcoma-associated herpesvirus (KSHV) is causally linked to several acquired immunodeficiency syndrome-related malignancies, including Kaposi's sarcoma (KS), primary effusion lymphoma (PEL) and a subset of multicentric Castleman's disease. Regulation of viral lytic replication is critical to the initiation and progression of KS. Recently, we reported that herpes simplex virus type 1 (HSV-1) was an important cofactor that activated lytic cycle replication of KSHV. Here, we further investigated the possible signal pathways involved in HSV-1-induced reactivation of KSHV.</p> <p>Results</p> <p>By transfecting a series of dominant negative mutants and protein expressing constructs and using pharmacologic inhibitors, we found that either Janus kinase 1 (JAK1)/signal transducer and activator of transcription 3 (STAT3) or JAK1/STAT6 signaling failed to regulate HSV-1-induced KSHV replication. However, HSV-1 infection of BCBL-1 cells activated phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB, also called AKT) pathway and inactivated phosphatase and tensin homologue deleted on chromosome ten (PTEN) and glycogen synthase kinase-3β (GSK-3β). PTEN/PI3K/AKT/GSK-3β pathway was found to be involved in HSV-1-induced KSHV reactivation. Additionally, extracellular signal-regulated protein kinase (ERK) mitogen-activated protein kinase (MAPK) pathway also partially contributed to HSV-1-induced KSHV replication.</p> <p>Conclusions</p> <p>HSV-1 infection stimulated PI3K/AKT and ERK MAPK signaling pathways that in turn contributed to KSHV reactivation, which provided further insights into the molecular mechanism controlling KSHV lytic replication, particularly in the context of HSV-1 and KSHV co-infection.</p

Optical-controlled ultrafast dynamics of skyrmion in antiferromagnets

Optical vortex, a light beam carrying orbital angular momentum (OAM) has been realized in experiments, and its interactions with magnets show abundant physical characteristics and great application potentials. In this work, we propose that optical vortex can control skyrmion ultrafast in antiferromagnets using numerical and analytical methods. Isolated skyrmion can be generated/erased in a very short time ~ps by beam focusing. Subsequently, the OAM is transferred to the skyrmion and results in its rotation motion. Different from the case of ferromagnets, the rotation direction can be modulated through tuning the light frequency in antiferromagnets, allowing one to control the rotation easily. Furthermore, the skyrmion Hall motion driven by multipolar spin waves excited by optical vortex is revealed numerically, demonstrating the dependence of the Hall angle on the OAM quantum number. This work unveils the interesting optical-controlled skyrmion dynamics in antiferromagnets, which is a crucial step towards the development of optics and spintronics.Comment: 19 pages, 6 figure