Vascular niche IL-6 induces alternative macrophage activation in glioblastoma through HIF-2α.

Spatiotemporal regulation of tumor immunity remains largely unexplored. Here we identify a vascular niche that controls alternative macrophage activation in glioblastoma (GBM). We show that tumor-promoting macrophages are spatially proximate to GBM-associated endothelial cells (ECs), permissive for angiocrine-induced macrophage polarization. We identify ECs as one of the major sources for interleukin-6 (IL-6) expression in GBM microenvironment. Furthermore, we reveal that colony-stimulating factor-1 and angiocrine IL-6 induce robust arginase-1 expression and macrophage alternative activation, mediated through peroxisome proliferator-activated receptor-γ-dependent transcriptional activation of hypoxia-inducible factor-2α. Finally, utilizing a genetic murine GBM model, we show that EC-specific knockout of IL-6 inhibits macrophage alternative activation and improves survival in the GBM-bearing mice. These findings illustrate a vascular niche-dependent mechanism for alternative macrophage activation and cancer progression, and suggest that targeting endothelial IL-6 may offer a selective and efficient therapeutic strategy for GBM, and possibly other solid malignant tumors

Thermal leptogenesis in a model with mass varying neutrinos

In this paper we consider the possibility of neutrino mass varying during the evolution of the Universe and study its implications on leptogenesis. Specifically, we take the minimal seesaw model of neutrino masses and introduce a coupling between the right-handed neutrinos and the dark energy scalar field, the Quintessence. In our model, the right-handed neutrino masses change as the Quintessence scalar evolves. We then examine in detail the parameter space of this model allowed by the observed baryon number asymmetry. Our results show that it is possible to lower the reheating temperature in this scenario in comparison with the case that the neutrino masses are unchanged, which helps solve the gravitino problem. Furthermore, a degenerate neutrino mass patten with $m_i$ larger than the upper limit given in the minimal leptogenesis scenario is permitted.Comment: 18 pages, 7 figures, version to appear in PR

p53 Is Necessary for the Apoptotic Response Mediated by a Transient Increase of Ras Activity

The tumor suppressor p53 eliminates cancer-prone cells via multiple mechanisms, including apoptosis. Ras elicits apoptosis in cells after protein kinase C (PKC) downregulation. However, the role of p53 in Ras-mediated apoptosis has not been fully investigated. Here, we demonstrate that mouse fibroblasts that express wild-type p53 are more susceptible to apoptosis elicited by PKC inhibition if Ras is transiently expressed or upregulated as opposed to stably expressed. In the latter case, p53 is frequently mutated. Transiently increased Ras activity induces Bax, and PKC inhibition augments this induction. Overexpression of E6 inactivates p53 and thereby suppresses both Bax induction and apoptosis. In contrast, Bax is not induced in stable ras transfectants, regardless of PKC inhibition. The data suggest that short- and long-term activation of Ras use a different mechanism(s) to initiate apoptosis. The status of p53 may contribute to such differences

The Impact of Oxidative Stress on the Bone System in Response to the Space Special Environment

The space special environment mainly includes microgravity, radiation, vacuum and extreme temperature, which seriously threatens an astronaut’s health. Bone loss is one of the most significant alterations in mammalians after long-duration habitation in space. In this review, we summarize the crucial roles of major factors—namely radiation and microgravity—in space in oxidative stress generation in living organisms, and the inhibitory effect of oxidative stress on bone formation. We discussed the possible mechanisms of oxidative stress-induced skeletal involution, and listed some countermeasures that have therapeutic potentials for bone loss via oxidative stress antagonism. Future research for better understanding the oxidative stress caused by space environment and the development of countermeasures against oxidative damage accordingly may facilitate human beings to live more safely in space and explore deeper into the universe

Machine Learning in Neuroimaging: A New Approach to Understand Acupuncture for Neuroplasticity

The effects of acupuncture facilitating neural plasticity for treating diseases have been identified by clinical and experimental studies. In the last two decades, the application of neuroimaging techniques in acupuncture research provided visualized evidence for acupuncture promoting neuroplasticity. Recently, the integration of machine learning (ML) and neuroimaging techniques becomes a focus in neuroscience and brings a new and promising approach to understand the facilitation of acupuncture on neuroplasticity at the individual level. This review is aimed at providing an overview of this rapidly growing field by introducing the commonly used ML algorithms in neuroimaging studies briefly and analyzing the characteristics of the acupuncture studies based on ML and neuroimaging, so as to provide references for future research

Associations between Dengue Incidence, Ecological Factors, and Anthropogenic Factors in Singapore

Singapore experiences endemic dengue. Vector control remains the primary means to reduce transmission due to the lack of available therapeutics. Resource limitations mean that vector-control tools need to be optimized, which can be achieved by studying risk factors related to disease transmission. We developed a statistical modelling framework which can account for a high-resolution and high-dimensional set of covariates to delineate spatio-temporal characteristics that are associated with dengue transmission from 2014 to 2020 in Singapore. We applied the proposed framework to two distinct datasets, stratified based on the primary type of housing within each spatial unit. Generalized additive models reveal non-linear exposure responses between a large range of ecological and anthropogenic factors as well as dengue incidence rates. At values below their mean, lesser mean total daily rainfall (Incidence rate ratio (IRR): 3.75, 95% CI: 1.00–14.05, Mean: 4.40 mm), decreased mean windspeed (IRR: 3.65, 95% CI: 1.87–7.10, Mean: 4.53 km/h), and lower building heights (IRR: 2.62, 95% CI: 1.44–4.77, Mean: 6.5 m) displayed positive associations, while higher than average annual NO2 concentrations (IRR: 0.35, 95% CI: 0.18–0.66, Mean: 13.8 ppb) were estimated to be negatively associated with dengue incidence rates. Our study provides an understanding of associations between ecological and anthropogenic characteristics with dengue transmission. These findings help us understand high-risk areas of dengue transmission, and allows for land-use planning and formulation of vector control policies

Mesenchymal Stem Cell Migration during Bone Formation and Bone Diseases Therapy

During bone modeling, remodeling, and bone fracture repair, mesenchymal stem cells (MSCs) differentiate into chondrocyte or osteoblast to comply bone formation and regeneration. As multipotent stem cells, MSCs were used to treat bone diseases during the past several decades. However, most of these implications just focused on promoting MSC differentiation. Furthermore, cell migration is also a key issue for bone formation and bone diseases treatment. Abnormal MSC migration could cause different kinds of bone diseases, including osteoporosis. Additionally, for bone disease treatment, the migration of endogenous or exogenous MSCs to bone injury sites is required. Recently, researchers have paid more and more attention to two critical points. One is how to apply MSC migration to bone disease therapy. The other is how to enhance MSC migration to improve the therapeutic efficacy of bone diseases. Some considerable outcomes showed that enhancing MSC migration might be a novel trick for reversing bone loss and other bone diseases, such as osteoporosis, fracture, and osteoarthritis (OA). Although plenty of challenges need to be conquered, application of endogenous and exogenous MSC migration and developing different strategies to improve therapeutic efficacy through enhancing MSC migration to target tissue might be the trend in the future for bone disease treatment

Xihuang Pill Induces Apoptosis of Human Glioblastoma U-87 MG Cells via Targeting ROS-Mediated Akt/mTOR/FOXO1 Pathway

Xihuang pill (XHP), a traditional Chinese herbal formula, has long been used as an effective agent against multiple tumors. The aim of this study is to evaluate the effects of XHP on the growth inhibition and apoptosis in glioblastoma U-87 MG cells. Gas chromatography-mass spectrometry (GC-MS) was performed for constituent analysis of XHP. Cell viability, cell cycle arrest, generation of reactive oxygen species (ROS), and apoptosis were measured by CCK-8 assay, PI/RNase staining, DCFH-DA assay, TUNEL assay, Annexin V-FITC/PI double staining, and JC-1 assay, respectively. The role of XHP in the regulation of Akt/mTOR/FOXO1 interaction was clarified by using Western Blotting (WB), immunofluorescence (IF), pharmacological inhibitor or antioxidant, and siRNA silencing. The results suggested that XHP could inhibit U-87 MG cells growth and arrest cells in S-phase cell cycle significantly and that the generation of ROS, collapse of mitochondrial membrane potential, enhancement of Bax/Bcl-xL ratio, and reduction of the precursor forms of caspase-9 and caspase-3 caused by XHP prompted that a ROS-mediated mitochondria-dependent apoptosis was possibly involved. Furthermore, XHP affected the Akt/mTOR/FOXO1 pathway via inhibiting the phosphorylation of Akt, mTOR, and FOXO1 and increasing both prototype and nuclear translocation of FOXO1. Inhibition of Akt, mTOR, and FOXO1 by specific inhibitors or siRNA could interpose the apoptotic induction. In conclusion, we demonstrate for the first time that XHP may regulate glioblastoma U-87 MG cell apoptosis via ROS-mediated Akt/mTOR/FOXO1 pathway