Search

Despite its excellent strengthening abilities, incorporation of C into most non-ferrous metals is limited by its solubility. In this study, C diffusion in pure Ti powders was promoted in a quantifiable amount using a combined technique of spark plasma sintering and powder metallurgy to synthesize a bulk Ti alloy. The sintered Ti was free from elements toxic to the human body and showed excellent strength, ductility, and wear resistance, which well exceeded those of the commercial Ti–6Al–4V alloy counterpart. Here, we report on the physics underlying the alloy design, its synthesis, resultant properties, and possible applications. [ABSTRACT FROM AUTHOR]

Feasibility studies were performed to determine the suitability of a novel synthesis technique for fabricating multifunctional composite materials for orthopedic implants. By blending paramagnetic Ti powder with diamagnetic graphite and consolidating the resulting mixtures, Ti–C composites that cannot be feasibly obtained via conventional alloying techniques or ingot metallurgy were synthesized. The synthesized composite material exhibited extremely low magnetic susceptibility (χ = 67.6 × 10 −6 ), and, as a result, exhibited fewer artifacts during magnetic resonance imaging. The strength of the composite material (σ = 770 MPa) was such that it could support external loads to which the human body is subjected, but its Young’s modulus was low ( E = 81.9 GPa) such that it could mitigate the stress-shielding effect. The material was also free from toxic elements such as Al and V and, thus, can be considered less harmful. [ABSTRACT FROM AUTHOR]

Abstract: Prostate cancer is the most common malignancy among men. Prostate cancer-related deaths are largely attributable to the development of hormone resistance in the tumor. No effective chemotherapy has yet been developed for advanced prostate cancer. It is desirable if a drug can be delivered directly and specifically to prostate cancer cells. Stem cells have selective migration ability toward cancer cells and therapeutic genes can be easily transduced into stem cells. In one form of gene therapy for cancer, the stem cells carry a gene encoding an enzyme that transforms an inert prodrug into a toxic product. Cytosine deaminase (CD) transforms the pro-drug 5-fluorocytosine into highly cytotoxic 5-fluorouracil (5-FU). The migration of the genetically modified stem cells was monitored by molecular magnetic resonance imaging, after labeling the stem cells with fluorescent magnetic nanoparticles (MNPs). Human neural stem cells encoding CD (HB1.F3.CD) were prepared and labeled with MNP. In tumor-bearing C57B mice, systemically transplanted HB1.F3.CD stem cells migrated toward the tumor and in combination with prodrug 5-FC, the volume of tumor implant was significantly reduced. These findings may contribute to development of a new selective chemotherapeutic strategy against prostate cancer. [Copyright &y& Elsevier]

Strategies for cancer treatment have traditionally focused on suppressing cancer cell behavior, but many recent studies have demonstrated that regulating the tumor microenvironment (TME) can also inhibit disease progression. Macrophages are major TME components, and the direction of phenotype polarization is known to regulate tumor behavior, with M2-like polarization promoting progression. It is also known that reactive oxygen species (ROS) in macrophages drive M2 polarization, and M2 polarization promote lung cancer progression. Lung cancer patients with lower expression of the antioxidant enzyme peroxiredoxin 5 (Prx5) demonstrate poorer survival. This study revealed that Prx5 deficiency in macrophages induced M2 macrophage polarization by lung cancer. We report that injection of lung cancer cells produced larger tumors in Prx5-deficit mice than wild-type mice independent of cancer cell Prx5 expression. Through co-culture with lung cancer cell lines, Prx5-deficient macrophages exhibited M2 polarization, and reduced expression levels of the M1-associated inflammatory factors iNOS, TNFα, and Il-1β. Moreover, these Prx5-deficient macrophages promoted the proliferation and migration of co-cultured lung cancer cells. Conversely, suppression of ROS generation by N-acetyl cysteine (NAC) inhibited the M2-like polarization of Prx5-deficient macrophages, increased expression levels of inflammatory factors, inhibited the proliferation and migration of co-cultured lung cancer cells, and suppressed tumor growth in mice. These findings suggest that blocking the M2 polarization of macrophages may promote lung cancer regression. [Display omitted] • Increased lung cancer cell proliferation in Prx5 -/- mice. • Deficiency of Prx5 in macrophages increased susceptibility to M2 macrophage polarization by lung cancer cells. • Deficiency of Prx5 in macrophages promoted lung cancer development. • Macrophage Prx5 has a pivotal role in macrophage polarization. [ABSTRACT FROM AUTHOR]

Recently, Parkin has been reported to induce endoplasmic reticulum (ER) stress. In addition, amyloid beta oligomers (AβO), hallmarks of Alzheimer's disease (AD), also increase ER stress in neurons. Because a mutation in the Parkin gene is a well-known predominant cause of familial Parkinson's disease (PD), Parkin has been well studied in PD but has not been well researched in AD. In this study, we investigated the role of AβO-mediated Parkin associated with ER stress in AD. For AD-based research, we used AβO treatments in mouse hippocampus-derived HT-22 cells. We stably expressed Parkin in HT-22 cells to confirm the hypothesis and used siParkin for downregulation of Parkin expression. Moreover, using hippocampi from amyloid precursor protein/presenilin 1/Tau triple transgenic mice (3xTg‐AD mice), which are used for AD models, we confirmed the relationship between ER stress and Parkin in vivo. We observed that ATF4 upregulated AβO-increases in Parkin. Parkin overexpression aggravated ER stress in AβO-treated HT-22 cells and the hippocampi of 3xTg‐AD mice. Parkin downregulation led to no significant change when compared to AβO-treated cells. Moreover, Parkin-mediated ER stress was not related to oxidative stress. Our study indicates that AβO-induced ATF4 upregulated Parkin levels and that Parkin increases ER stress as a positive feedback loop. Through this study, our findings provide a foundation for future studies on the specific mechanisms related to the role of Parkin in AD. • In HT-22, AβO-mediated ER-stress increased Parkin expression. • AβO-mediated Parkin upregulated ER-stress as positive feedback. • AβO-mediated Parkin level was not related with oxidative stress. [ABSTRACT FROM AUTHOR]

Abstract: Aging is characterized by progressive loss of cognitive and memory functions as well as decrease in physical activities. In the present study, a human neural stem cell line (F3 NSC) over-expressing choline acetyltransferase (F3.ChAT), an enzyme responsible for acetylcholine synthesis, was generated and transplanted in the brain of 18-month-old male ICR mice. Four weeks post-transplantation, neurobehavioral functions, expression of ChAT enzyme, production of acetylcholine and neurotrophic factors, and expression of cholinergic nervous system markers in transplanted animals were investigated. F3.ChAT NSCs markedly improved both the cognitive function and physical activity of aging animals, in parallel with the elevation of brain acetylcholine level. Transplanted F3 and F3.ChAT cells were found to differentiate into neurons and astrocytes, and to produce ChAT proteins. Transplantation of the stem cells increased brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF), enhanced expression of Trk B, and restored host microtubule-associated protein 2 and cholinergic nervous system. The results demonstrate that human NSCs over-expressing ChAT improve cognitive function and physical activity of aging mice, not only by producing ACh directly but also by restoring cholinergic neuronal integrity, which might be mediated by neurotrophins BDNF and NGF. [Copyright &y& Elsevier]

Abstract: Neural stem cells (NSCs) led to the development of a novel strategy for delivering therapeutic genes to tumors. NSCs expressing rabbit carboxyl esterase (F3.CE), which activates CPT-11, significantly inhibited the growth of MDA-MB-435 cells in the presence of CPT-11. F3.CE cells migrated selectively into the brain metastases located in the opposite hemisphere. The treatment also significantly decreased tumor volume in immune-deficient mice bearing MDA-MB-435 tumors when F3.CE cells were transplanted into the contralateral hemisphere. The survival rate was significantly prolonged with the treatment with F3.CE and CPT-11. This strategy may be considered as an effective treatment regimen for brain metastases. [Copyright &y& Elsevier]