Resveratrol-induced cytotoxicity in human Burkitt's lymphoma cells is coupled to the unfolded protein response

<p>Abstract</p> <p>Background</p> <p>Resveratrol (RES), a natural phytoalexin found at high levels in grapes and red wine, has been shown to induce anti-proliferation and apoptosis of human cancer cell lines. However, the underlying molecular mechanisms are at present only partially understood.</p> <p>Method</p> <p>The effects of RES on activation of unfolded protein responses (UPR) were evaluated using Western blotting, semi-quantitative and real-time RT-PCR. Cell death was evaluated using Annexin V/PI staining and subsequent FACS.</p> <p>Results</p> <p>Similar as tunicamycin, treatment with RES lead to the activation of all 3 branches of the UPR, with early splicing of XBP-1 indicative of IRE1 activation, phosphorylation of eIF2α consistent with ER resident kinase (PERK) activation, activating transcription factor 6 (ATF6) splicing, and increase in expression levels of the downstream molecules GRP78/BiP, GRP94 and CHOP/GADD153 in human Burkitt's lymphoma Raji and Daudi cell lines. RES was shown to induce cell death, which could be attenuated by thwarting upregulation of CHOP.</p> <p>Conclusions</p> <p>Our data suggest that activation of the apoptotic arm of the UPR and its downstream effector CHOP/GADD153 is involved, at least in part, in RES-induced apoptosis in Burkitt's lymphoma cells.</p

Molecular properties of CD133+ glioblastoma stem cells derived from treatment-refractory recurrent brain tumors

Glioblastoma multiforme (GBM) remains refractory to conventional therapy. CD133+ GBM cells have been recently isolated and characterized as chemo-/radio-resistant tumor-initiating cells and are hypothesized to be responsible for post-treatment recurrence. In order to explore the molecular properties of tumorigenic CD133+ GBM cells that resist treatment, we isolated CD133+ GBM cells from tumors that are recurrent and have previously received chemo-/radio-therapy. We found that the purified CD133+ GBM cells sorted from the CD133+ GBM spheres express SOX2 and CD44 and are capable of clonal self-renewal and dividing to produce fast-growing CD133− progeny, which form the major cell population within GBM spheres. Intracranial injection of purified CD133+, not CD133− GBM daughter cells, can lead to the development of YKL-40+ infiltrating tumors that display hypervascularity and pseudopalisading necrosis-like features in mouse brain. The molecular profile of purified CD133+ GBM cells revealed characteristics of neuroectoderm-like cells, expressing both radial glial and neural crest cell developmental genes, and portraying a slow-growing, non-differentiated, polarized/migratory, astrogliogenic, and chondrogenic phenotype. These data suggest that at least a subset of treated and recurrent GBM tumors may be seeded by CD133+ GBM cells with neural and mesenchymal properties. The data also imply that CD133+ GBM cells may be clinically indolent/quiescent prior to undergoing proliferative cell division (PCD) to produce CD133− GBM effector progeny. Identifying intrinsic and extrinsic cues, which promote CD133+ GBM cell self-renewal and PCD to support ongoing tumor regeneration may highlight novel therapeutic strategies to greatly diminish the recurrence rate of GBM

Nucleus disc arthroplasty with the NUBAC™ device: 2-year clinical experience

Low back pain (LBP) due to degenerative disc disease (DDD) is a common condition that can be treated along a continuum of care: from conservative therapies to several surgical choices. Nucleus arthroplasty is an emerging technology that could potentially fill part of the gap in the spine continuum of care. The introduction of recent technologies that allow the replacement of the degenerated disc nucleus using prosthetic devices may be considered an additional therapeutic tool that can be used by the surgeon in selected cases of LBP due to DDD. Nucleus arthroplasties are designed to treat early stages of DDD, which are one of the most common spinal disorders in the population under 65 years of age. NUBAC™ is the first articulating nucleus disc prosthesis, designed to optimally respect the lumbar anatomy, kinematics, and biomechanics, constructed in unique two-piece manufactured from polyetheretherketone (PEEK) with an inner ball/socket articulation. The optimal indications for NUBAC™ implantation are: disc height >5 mm, degenerative disc changes at an early stage (Pfirmann 2, 3), single level affection, integrity of posterior facet joints, lack of local anatomical contraindication, failure of conservative treatment for at least 6 months. From December 2006 to January 2009, a total of 39 patients underwent nucleus disc arthroplasty with NUBAC™ device. 22 cases have 2-year follow up. There have been no major intra-operative or post-operative vascular or neurological complications in this series. The data showed that there were significant decreases in both Visual Analogue Scale (VAS) and Oswestry Disability Index (ODI) after the procedure, with a meaningful improvement of symptoms in all patients. Although preliminary, the initial results are encouraging. The absence of any major intra-operative and post-operative complications supports the design rationale of the NUBAC™, being less invasive comparing to total disc replacement (TDA) and with a low rate of surgical risk. The effectiveness of data as seen in 2-year follow-up on both VAS and ODI have also suggested that the NUBAC™ could be considered a viable treatment option for patients with LBP caused by DDD

SOMA T3A for solving the 100-Digit Challenge

In this paper, we address 10 basic test functions of the 100-Digit Challenge of the SEMCCO 2019 & FANCCO 2019 Competition by using team-to-team adaptive seft-organizing migrating algorithm - SOMA T3A with many improvements in the Organization, Migration, and Update process, as well as the linear adaptive PRT and the cosine-based adaptive Step. The results obtained from the algorithm on the 100-Digit Challenge are very promising with 93 points in total. © Springer Nature Switzerland AG 2020