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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 541 records · Page 30
All sourcesNASA NTRSDOE OSTI
DOE OSTI2019

Cellular Composition and Expression of Cell Proliferation and Apoptosis Markers in Bone Marrow Cells after Heterotransplantation

The effects of heterotransplantation on bone marrow structures were studied in experimental male mice. Suspension of the bone marrow from feline femur (1 ml bone marrow diluted in isotonic saline, 1:2) was injected into the caudal vein. Heterotransplantation led to an increase in the level of serotonin involved in cell differentiation. In 2 days, the counts of all cells except erythroid cells decreased. Immunohistochemical analysis of Ki-67 marker within 40 min after transplantation showed a significant increase of cell proliferative activity in comparison with that in intact mice. At later terms, the expression of Ki-67 in bone marrow cells decreased, while the expression of apoptosis regulator P-53 increased, which was associated with the presence of numerous dead cells.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

Ectopic expression of anti-HIV-1 shRNAs protects CD8{sup +} T cells modified with CD4ζ CAR from HIV-1 infection and alleviates impairment of cell proliferation

Chimeric antigen receptors (CARs) are artificially engineered receptors that confer a desired specificity to immune effector T cells. As an HIV-1-specific CAR, CD4ζ CAR has been extensively tested in vitro as well as in clinical trials. T cells modified with this CAR mediated highly potent anti-HIV-1 activities in vitro and were well-tolerated in vivo, but exerted limited effects on viral load and reservoir size due to poor survival and/or functionality of the transduced cells in patients. We hypothesize that ectopic expression of CD4ζ on CD8{sup +} T cells renders them susceptible to HIV-1 infection, resulting in poor survival of those cells. To test this possibility, highly purified CD8{sup +} T cells were genetically modified with a CD4ζ-encoding lentiviral vector and infected with HIV-1. CD8{sup +} T cells were vulnerable to HIV-1 infection upon expression of CD4ζ as evidenced by elevated levels of p24{sup Gag} in cells and culture supernatants. Concurrently, the number of CD4ζ-modified CD8{sup +} T cells was reduced relative to control cells upon HIV-1 infection. To protect these cells from HIV-1 infection, we co-expressed two anti-HIV-1 shRNAs previously developed by our group together with CD4ζ. This combination vector was able to suppress HIV-1 infection without impairing HIV-1-dependent effector activities of CD4ζ. In addition, the number of CD4ζ-modified CD8{sup +} T cells maintained similar levels to that of the control even under HIV-1 infection. These results suggest that protecting CD4ζ-modified CD8{sup +} T cells from HIV-1 infection is required for prolonged HIV-1-specific immune surveillance. - Highlights: • Ectopic expression of CD4ζ CAR in CD8{sup +} T cells renders them susceptible to HIV-1 infection. • Co-expression of two anti-HIV-1 shRNAs protects CD4ζ CAR-modified CD8{sup +} T cells from HIV-1 infection. • Protecting CD4ζ CAR-modified CD8{sup +} T cells from HIV-1 infection suppresses its cytopathic effect.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

IL-8 interacts with metadherin promoting proliferation and migration in gastric cancer

It has been reported that IL-8 was involved in the promotion of invasion of Gastric Cancer (GC), however the underlying mechanism by which IL-8 was observed to be able to promote invasion remains unknown. Here, in our study, IL-8 was shown to be significantly up-regulated in GC compared with paired normal control tissues whose expression was markedly associated with inferior overall prognosis; and IL-8 was displayed to be capable of directly interacting with metadherin (MTDH), which in turn can up-regulate IL-8 expression. Blockage of IL-8/MTDH using specific mono-antibody can abolish the invasion IL-8 mediated. Taken together, our results may provide a novel explanation of working mechanism of IL-8 in the invasion of GC. - Highlights: • IL-8 was commonly observed to be significantly up-regulated in gastric cancer. • IL-8 was found to be able to be directly interacted with MTDH. • MTDH can up-regulate IL-8 promoting EMT process. • Blockage of IL-8-MTDH complex can abrogate the growth of gastric cancer cells in vitro and in vivo.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

STAT3 stimulates adipogenic stem cell proliferation and cooperates with HMGA2 during the early stage of differentiation to promote adipogenesis

Signal transducer and activator of transcription 3 (STAT3) is abundantly expressed in the adipose tissue of obese mice and humans, but the role of STAT3 in adipogenesis is still not fully understood. In the present study, we discovered an activation of STAT3 during the early differentiation stage of mouse 3T3-L1 preadipocytes. Stat3 knockdown using siRNA blocked cell cycle progression of both preadipoctes and early differentiating cells. Moreover, accumulation of lipid droplets was inhibited by Stat3 knockdown. Importantly, in the nucleus of early differentiating cells, we demonstrated that STAT3 protein co-localized with high-mobility-group protein AT-hook 2 (HMGA2), which was reported to promote adipogenesis in a previous study. Taken together, our data indicate that STAT3 and HMGA2 cooperatively promote adipogenesis which highlight a more detail understanding of STAT3 related transcription factor network during adipogenesis. - Highlights: • We discovered an activation of STAT3 during the early differentiation stage of mouse 3T3-L1 preadipocytes. • Stat3 knockdown using siRNA blocked cell cycle progression of both preadipoctes and early differentiating cells. • Accumulation of lipid droplets was inhibited by Stat3 knockdown. • STAT3 protein co-localized with HMGA2, which was reported to promote adipogenesis in a previous study.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

MiR-223 modulates hepatocellular carcinoma cell proliferation through promoting apoptosis via the Rab1-mediated mTOR activation

Hepatocellular carcinoma (HCC) is a common digestive malignancy. MiR-223, a well-identified miRNA, exhibits diverse properties in different cancers. In this study, we demonstrated that miR-223 could suppress cell growth and promote apoptosis in HepG2 and Bel-7402 HCC cell lines. We screened and identified a novel miR-223 target, Ras-related protein Rab-1(Rab1). Upregulation of miR-223 would specifically and markedly down-regulate Rab1 expression. In addition, miR-223-overexpressing subclones showed significant cell growth inhibition by increasing cell apoptosis in HepG2 and Bel-7402 cells. To identify the mechanisms, we firstly investigated the mTOR pathway and found that pmTOR, p70S6K and Bcl-2 were dramatically down-regulated after miR-223 transfection, while no changes in the level of Bax was visualized. Furthermore, our data showed that the anti-tumor effects arising from miR-223 transfection in HCC cells may be due to the deactivation of mTOR pathway caused by the suppression of Rab1 expression when miR-223 is overexpressed. In summary, our results indicate that miR-223 functions as a tumor suppressor and plays a critical role in inhibiting the tumorigenesis and promoting the apoptosis of HCC through the mTOR signaling pathway in vitro. By targeting Rab1, miR-223 efficiently mediates the mTOR pathway. Given these, miR-223 may be a potential therapeutic target for treating HCC. - Highlights: • miR-223 is downregulated in hepatocellular carcinomas. • Rab1 is a novel downstream target of miR-223. • miR-223 suppressed cell growth and enhanced apoptosis in HepG2 and Bel-7402 cells. • miR-223 modulated mTOR signaling pathway by targeting Rab1.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

Heparanase-1-induced shedding of heparan sulfate from syndecan-1 in hepatocarcinoma cell facilitates lymphatic endothelial cell proliferation via VEGF-C/ERK pathway

Heparanase-1/syndecan-1 axis plays critical roles in tumorigenesis and development. The main mechanism includes heparanase-1 (HPA-1) degrades the heparan sulfate chain of syndecan-1 (SDC-1), and the following shedding of heparan sulfate from tumor cell releases and activates SDC-1 sequestered growth factors. However, the significance of Heparanase-1/syndecan-1 axis and its effects on the microenvironment of lymphatic metastasis in hepatocellular carcinogenesis (HCC) procession have not been reported. Herein, we found that HPA-1 could degrade the heparan sulfate on hepatocarcinoma cell surface. Importantly, HPA-1-induced shedding of heparan sulfate chain from SDC-1 facilitated the release of vascular endothelial growth factor C (VEGF-C) from SDC-1/VEGF-C complex into the medium of hepatocarcinoma cell. Further studies indicated that VEGF-C secretion from hepatocarcinoma cell promoted lymphatic endothelial cell growth through activating extracellular signal-regulated kinase (ERK) signaling. Taken together, this study reveals a novel existence of Heparanase-1/syndecan-1 axis in hepatocarcinoma cell and its roles in the cross-talking with the microenvironment of lymphatic metastasis. - Highlights: • SDC-1 anchors VEGF-C via its HS chains. • Secreted HPA-1 from hepatocarcinoma cell cleaves HS chains of SDC-1. • The shedding of SDC-1 HS chains releases VEGF-C from SDC-1/VEGF-C complex. • LMWH inhibits VEGF-C secretion through stabilizing SDC-1/VEGF-C complex. • VEGF-C secretion from hepatocarcinoma cell facilitates LEC growth via ERK signaling.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

Wnt signaling promotes androgen-independent prostate cancer cell proliferation through up-regulation of the hippo pathway effector YAP

Aberrant up-regulation of Wnt/β-catenin signaling is associated with the development and progression of prostate cancer, but the underlying mechanism is unclear. Here we show that in the absence of androgens, the Wnt/β-catenin pathway activates AR-mediated transcription through up-regulation of the Hippo pathway effector Yes-associated protein (YAP). Wnt3a-conditioned medium (Wnt3a-CM) promotes the growth of LNCaP cells and increases AR and YAP protein levels. Moreover, Wnt3a-CM induces the nuclear translocation of YAP and the AR, but not β-catenin, thereby activating the expression of AR- and YAP-dependent genes, in an androgen-independent manner. In addition, depletion of YAP with small interfering RNA (siRNA) prevented Wnt3a-CM-mediated up-regulation of AR-dependent gene expression. Thus, our findings provide mechanistic insight into the proposed cross-talk between the Wnt/β-catenin and Hippo pathways in androgen-independent prostate cancer development. - Highlights: • Wnt3a promotes androgen-independent prostate cancer cell growth. • Wnt3a activates YAP- and AR-mediated transcription in the absence of androgen. • YAP is required for Wnt3a-induced AR activation in the absence of androgen.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Scavenger receptor class B type 1 regulates neuroblastoma cell proliferation, migration and invasion

Neuroblastoma (NB) is an extra cranial pediatric embryonal tumor most prevalent in children less than 1 year of age. NB accounts for 7% of all pediatric cancers but accounts for 15% of all childhood cancer deaths. Scavenger receptor class B type 1 (SR-B1), a mediator of cellular cholesterol uptake, is overexpressed in and have been linked to the aggressiveness of many cancers. Nevertheless, no studies have so far investigated the relationship between SR-B1 and NB. Elucidation of receptors that promote NB may pave the way for discovery of new therapeutic targets. Here we show that inhibition of SR-B1 reduced cell survival, migration and invasion, and cholesterol content in NB cell lines. Additionally analysis of SR-B1 levels in NB patient biopsies using the R2: Genomics Analysis and Visualization Platform showed that high SR-B1 expression correlated with decreased overall and event-free survival.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

LncRNA MALAT1 promotes cell proliferation and imatinib resistance by sponging miR-328 in chronic myelogenous leukemia

Chronic myeloid leukemia (CML) is a type of cancer that starts in certain blood-forming cells of the bone marrow. LncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), a well known protooncogene, has be shown to be upregulated in various tumor types, including multiple myeloma. However, the biological function of MALAT1 in CML remains has yet to be explored. This study was designed to investigate the effects of MALAT1 on the physiological processes in CML and its underlying mechanisms, which will be helpful for us to have a better understanding of CML development and progression as well as improved therapeutic method.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

Authorship in Radiation Oncology: Proliferation Trends Over 30 Years

Purpose: To investigate authorship trends in the radiation oncology literature. Methods and Materials: We examined the authorship credits of “original research articles” within 2 popular radiation oncology journals–International Journal of Radiation Oncology, Biology, Physics and Radiotherapy and Oncology–in 1984, 1994, 2004, and 2014. We compared the number of authors per publication during these 4 time periods using simple linear regression as a test for trend. We investigated additional author characteristics in a subset of articles. Results: A total of 2005 articles were eligible. The mean number of authors per publication rose from 4.3 in 1984 to 9.1 in 2014 (P<.001). On subset analysis of 400 articles, there was an increase in the percentage of multidisciplinary bylines (from 52% to 72%), multi-institutional bylines (from 20% to 53%), and publications with a trainee first author (from 16% to 56%) during the study period. Conclusions: The mean number of authors per publication has more than doubled over the last 30 years in the radiation oncology literature. Possible explanations include increasingly complex and collaborative research as well as honorary authorship. Explicit documentation of author contributions could help ensure that scientific work is credited according to accepted standards.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2017

EVA1A inhibits GBM cell proliferation by inducing autophagy and apoptosis

Eva-1 homolog A (EVA1A) is a novel lysosome and endoplasmic reticulum-associated protein involved in autophagy and apoptosis. In this study, we constructed a recombinant adenovirus 5-EVA1A vector (Ad5-EVA1A) to overexpress EVA1A in glioblastoma (GBM) cell lines and evaluated its anti-tumor activities in vitro and in vivo. We found that overexpression of EVA1A in three GBM cell lines (U251, U87 and SHG44) resulted in a suppression of tumor cell growth via activation of autophagy and induction of cell apoptosis in a dose- and time-dependent manner. EVA1A-mediated autophagy was associated with inactivation of the mTOR/RPS6KB1 signaling pathway. Furthermore in vivo, overexpression of EVA1A successfully inhibited tumor growth in NOD/SCID mice. Our data suggest that EVA1A-induced autophagy and apoptosis play a role in suppressing the development of GBM and their up-regulation may be an effective method for treating this form of cancer. - Highlights: • Overexpression of EVA1A suppresses GBM cell growth. • EVA1A induces autophagy through the mTOR/RPS6KB1 pathway. • EVA1A induces GBM cell apoptosis. • EVA1A inhibits the development of GBM in vivo.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Sorafenib derivatives-functionalized gold nanoparticles confer protection against tumor angiogenesis and proliferation via suppression of EGFR and VEGFR-2

Sorafenib is a multi-kinase inhibitor that has been highlighted as a tumor suppressor due to its anti-proliferative and anti-angiogenic properties, whereas the clinical application of Sorafenib is restricted by the side effects it may cause. The past decade has witnessed the development of a series of sorafenib derivatives to improve the clinical performance of sorafenib. Gold nanoparticles (AuNPs) have been widely utilized in drug delivery systems due to their unique properties, including biocompatible nature, simple preparation, and easy surface modification. Herein, this study is aimed to investigate the anti-tumor effects of new sorafenib derivatives-capped gold nanoparticles (AuNPs-New Sor) in tumor formation and metastasis as well as the underlying mechanisms. Initially, new sorafenib derivatives were constructed and combined with AuNPs to form AuNPs-New Sor, and the properties of synthesized AuNPs-New Sor were identified in a mouse model of tumorigenesis. The effect of AuNPs-New Sor on tumor vascular normalization was investigated by assessing vascular permeability and perfusion rate. Next, we evaluated the effect of AuNPs-New Sor on migration and viability of tumor cells and human umbilical vein endothelial cells (HUVECs) as well as on HUVEC angiogenesis in vitro. A melanoma mouse model was further established for in vivo substantiation of the anti-tumor effect of AuNPs-New Sor. According to the results, AuNPs could deliver new sorafenib derivatives into tumor tissues and downregulate the expression of epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor-2 (VEGFR-2), thereby suppressing tumor migration, EMT, and angiogenesis in vitro. In addition, AuNPs-New Sor displayed competitive anti-tumor activities in vivo. Taken together, AuNPs-New Sor may attenuate tumor development and angiogenesis through downregulation of EGFR and VEGFR-2.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2025

Path Toward a Breeding, Proliferation-Resistant, Thermal-Spectrum Molten Salt Reactor

Liquid-fueled, thermal-spectrum molten salt breeder reactors (TS-MSBRs) offer the potential for affordable, safe, inexhaustible energy with minimal potential for nuclear material misuse and without significant actinide waste generation. Realizing the full set of TS-MSBR capabilities is only now becoming possible with the advent of advanced fuel-salt processing techniques, improved materials, and a more detailed understanding of fuel-salt properties. Additionally, modern higher-fidelity modeling and simulation methods enable a more detailed evaluation of TS-MSBR design options. TS-MSBRs, however, remain immature and will require substantial, sustained development resources.

11 NUCLEAR FUEL CYCLE AND FUEL MATERIALS↗