Browsing by Author "Song, Yang"

Now showing 1 - 6 of 6
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    Beyond VEGF: Targeting Inflammation and Other Pathways for Treatment of Retinal Disease
    (American Society for Pharmacology and Experimental Therapeutics, 2023) Muniyandi, Anbukkarasi; Hartman, Gabriella D.; Song, Yang; Mijit, Mahmut; Kelley, Mark R.; Corson, Timothy W.; Ophthalmology, School of Medicine
    Neovascular eye diseases include conditions such as retinopathy of prematurity, proliferative diabetic retinopathy, and neovascular age-related macular degeneration. Together, they are a major cause of vision loss and blindness worldwide. The current therapeutic mainstay for these diseases is intravitreal injections of biologics targeting vascular endothelial growth factor (VEGF) signaling. Lack of universal response to these anti-VEGF agents coupled with the challenging delivery method underscore a need for new therapeutic targets and agents. In particular, proteins that mediate both inflammatory and proangiogenic signaling are appealing targets for new therapeutic development. Here, we review agents currently in clinical trials and highlight some promising targets in preclinical and early clinical development, focusing on the redox-regulatory transcriptional activator APE1/Ref-1, the bioactive lipid modulator soluble epoxide hydrolase, the transcription factor RUNX1, and others. Small molecules targeting each of these proteins show promise for blocking neovascularization and inflammation. The affected signaling pathways illustrate the potential of new antiangiogenic strategies for posterior ocular disease. SIGNIFICANCE STATEMENT: Discovery and therapeutic targeting of new angiogenesis mediators is necessary to improve treatment of blinding eye diseases like retinopathy of prematurity, diabetic retinopathy, and neovascular age-related macular degeneration. Novel targets undergoing evaluation and drug discovery work include proteins important for both angiogenesis and inflammation signaling, including APE1/Ref-1, soluble epoxide hydrolase, RUNX1, and others.
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    Improved understanding of the spatially-heterogeneous relationship between satellite solar-induced chlorophyll fluorescence and ecosystem productivity
    (Elsevier, 2021-10) Song, Yang; Wang, Lixin; Wang, Jing; Earth Science, School of Science
    Satellite solar-induced chlorophyll fluorescence (SIF) is deemed as a good proxy for vegetation photosynthesis. To date, SIF has been shown to correlate strongly with gross primary productivity (GPP) at ecosystem scale and perform well in monitoring the impacts of extreme climate events on ecosystem productivity. However, the SIF-GPP relationship exhibits a spatially-heterogeneous pattern across ecosystems and produces both linear and nonlinear results at different spatiotemporal scales. Understanding of the different spatiotemporal SIF-GPP relationships is still incomplete and somewhat controversial in previous studies. Here, based on the light-use efficiency (LUE) models, this study investigated the spatially-heterogeneous SIF-GPP relationships across the conterminous United States (CONUS), and examined the possible drivers and mechanisms. Our results showed that SIF and GPP exhibited similar spatiotemporal patterns but responded differently to environmental factors (i.e., soil moisture, precipitation, photosynthetically active radiation, air temperature, and atmospheric vapor pressure deficit). The correlation analysis showed that the SIF-GPP relationships were spatially-heterogeneous across the CONUS both at monthly and annual scales. Moreover, our findings also indicated that different biome types could partly explain the spatial heterogeneity of SIF-GPP relationship. Different canopy structures and vegetation coverages across biomes could be primary drivers of the spatially-heterogeneous SIF-GPP relationship. In addition, the SIF-GPP relationships under the baseline and drought scenarios appeared to be similar and consistent. It implies that there could be an invariant SIF-GPP relationship under both drought and non-drought conditions, leading to a weak effect of interannual drought on the spatial heterogeneity. In summary, our results highlight that the effects of biome characteristics (Ωbiome) and environmental stresses (Φstress) on spatially-heterogeneous SIF-GPP relationship and further explore possible mechanisms of the linkage between SIF and GPP.
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    Increased Global Vegetation Productivity Despite Rising Atmospheric Dryness Over the Last Two Decades
    (AGU, 2022-07) Song, Yang; Jiao, Wenzhe; Wang, Jing; Wang, Lixin; Earth and Environmental Sciences, School of Science
    Rising atmospheric dryness [vapor pressure deficit (VPD)] can limit photosynthesis and thus reduce vegetation productivity. Meanwhile, plants can benefit from global warming and the fertilization effect of carbon dioxide (CO2). There are growing interests to study climate change impacts on terrestrial vegetation. However, global vegetation productivity responses to recent climate and CO2 trends remain to be fully understood. Here, we provide a comprehensive evaluation of the relative impacts of VPD, temperature, and atmospheric CO2 concentration on global vegetation productivity over the last two decades using a robust ensemble of solar-induced chlorophyll fluorescence (SIF) and gross primary productivity (GPP) data. We document a significant increase in global vegetation productivity with rising VPD, temperature, and atmospheric CO2 concentration over this period. For global SIF (or GPP), the decrease due to rising VPD was comparable to the increase due to warming but far less than the increase due to elevated CO2 concentration. We found that rising VPD counteracted only a small proportion (approximately 8.1%–15.0%) of the warming and CO2-induced increase in global SIF (or GPP). Despite the sharp rise in atmospheric dryness imposing a negative impact on plants, the warming and CO2 fertilization effects contributed to a persistent and widespread increase in vegetation productivity over the majority (approximately 66.5%–72.2%) of the globally vegetated areas. Overall, our findings provide a quantitative and comprehensive attribution of rising atmospheric dryness on global vegetation productivity under concurrent climate warming and CO2 increasing.
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    MicroRNA410 Inhibits Pulmonary Vascular Remodeling via Regulation of Nicotinamide Phosphoribosyltransferase
    (Springer Nature, 2019-07-09) Gao, Hui; Chen, Jiwang; Chen, Tianji; Wang, Yifang; Song, Yang; Dong, Yangbasai; Zhao, Shuangping; Machado, Roberto F.; Department of Medicine, IU School of Medicine
    Nicotinamide phosphoribosyltransferase (NAMPT) upregulation in human pulmonary artery endothelial cells (hPAECs) is associated with pulmonary arterial hypertension (PAH) progression and pulmonary vascular remodeling. The underlying mechanisms regulating NAMPT expression are still not clear. In this study, we aimed to study the regulation of NAMPT expression by microRNA410 (miR410) in hPAECs and explore the role of miR410 in the pathogenesis of experimental pulmonary hypertension. We show that miR410 targets the 3' UTR of NAMPT and that, concomitant with NAMPT upregulation, miR410 is downregulated in lungs of mice exposed to hypoxia-induced pulmonary hypertension (HPH). Our results also demonstrate that miR410 directly inhibits NAMPT expression. Overexpression of miR410 in hPAECs inhibits basal and VEGF-induced proliferation, migration and promotes apoptosis of hPAECs, while miR410 inhibition via antagomirs has the opposite effect. Finally, administration of miR410 mimics in vivo attenuated induction of NAMPT in PAECs and prevented the development of HPH in mice. Our results highlight the role of miR410 in the regulation of NAMPT expression in hPAECs and show that miR410 plays a potential role in PAH pathobiology by targeting a modulator of pulmonary vascular remodeling.
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    Satellite Solar-Induced Chlorophyll Fluorescence Reveals Heat Stress Impacts on Wheat Yield in India
    (MDPI, 2020) Song, Yang; Wang, Jing; Wang, Lixin; Earth Sciences, School of Science
    With continued global warming, the frequency and severity of heat wave events increased over the past decades, threatening both regional and global food security in the future. There are growing interests to study the impacts of drought on crop. However, studies on the impacts of heat stress on crop photosynthesis and yield are still lacking. To fill this knowledge gap, we used both statistical models and satellite solar-induced chlorophyll fluorescence (SIF) data to assess the impacts of heat stress on wheat yield in a major wheat growing region, the Indo-Gangetic Plains (IGP), India. The statistical model showed that the relationships between different accumulated degree days (ADD) and reported wheat yield were significantly negative. The results confirmed that heat stress affected wheat yield across this region. Building on such information, satellite SIF observations were used to further explore the physiological basis of heat stress impacts on wheat yield. Our results showed that SIF had strong negative correlations with ADDs and was capable of monitoring heat stress. The SIF results also indicated that heat stress caused yield loss by directly impacting the photosynthetic capacity in wheat. Overall, our findings demonstrated that SIF as an effective proxy for photosynthetic activity would improve our understanding of the impacts of heat stress on wheat yield.
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    Wnt3a-induced ST2 decellularized matrix ornamented PCL scaffold for bone tissue engineering
    (Tech Science Press, 2022) Wang, Xiaofang; Tu, Xiaolin; Ma, Yufei; Chen, Jie; Song, Yang; Liu, Guangliang; Anatomy, Cell Biology and Physiology, School of Medicine
    The limited bioactivity of scaffold materials is an important factor that restricts the development of bone tissue engineering. Wnt3a activates the classic Wnt/β-catenin signaling pathway which effects bone growth and development by the accumulation of β-catenin in the nucleus. In this study, we fabricated 3D printed PCL scaffold with Wnt3a-induced murine bone marrow-derived stromal cell line ST2 decellularized matrix (Wnt3a-ST2-dCM-PCL) and ST2 decellularized matrix (ST2-dCM-PCL) by freeze-thaw cycle and DNase decellularization treatment which efficiently decellularized >90% DNA while preserved most protein. Compared to ST2-dCM-PCL, Wnt3a-ST2-dCM-PCL significantly enhanced newly-seeded ST2 proliferation, osteogenic differentiation and upregulated osteogenic marker genes alkaline phosphatase (Alp), Runx2, type I collagen (Col 1) and osteocalcin (Ocn) mRNA expression. After 14 days of osteogenic induction, Wnt3a-ST2-dCM-PCL promoted ST2 mineralization. These results demonstrated that Wnt3a-induced ST2 decellularized matrix improve scaffold materials’ osteoinductivity and osteoconductivity.