Browsing by Author "Li, Junjie"

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    Cholesteryl Ester Accumulation Induced by PTEN Loss and PI3K/AKT Activation Underlies Human Prostate Cancer Aggressiveness
    (Elsevier, 2014-03-04) Yue, Shuhua; Li, Junjie; Lee, Seung-Young; Lee, Hyeon Jeong; Shao, Tian; Song, Bing; Cheng, Liang; Masterson, Timothy A.; Liu, Xiaoqi; Ratliff, Timothy L.; Cheng, Ji-Xin; Department of Pathology & Laboratory Medicine, IU School of Medicine
    Altered lipid metabolism is increasingly recognized as a signature of cancer cells. Enabled by label-free Raman spectromicroscopy, we performed quantitative analysis of lipogenesis at single cell level in human patient cancerous tissues. Our imaging data revealed an unexpected, aberrant accumulation of esterified cholesterol in lipid droplets of high-grade prostate cancer and metastases. Biochemical study showed that such cholesteryl ester accumulation was a consequence of loss of tumor suppressor PTEN and subsequent activation of PI3K/AKT pathway in prostate cancer cells. Furthermore, we found that such accumulation arose from significantly enhanced uptake of exogenous lipoproteins and required cholesterol esterification. Depletion of cholesteryl ester storage significantly reduced cancer proliferation, impaired cancer invasion capability, and suppressed tumor growth in mouse xenograft models with negligible toxicity. These findings open opportunities for diagnosing and treating prostate cancer by targeting the altered cholesterol metabolism.
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    Fabrication of B doped g-C3N4/TiO2 heterojunction for efficient photoelectrochemical water oxidation
    (Elsevier, 2018) Kong, Weiqian; Zhang, Xiaofan; Chang, Binbin; Zhou, Yannan; Zhang, Shouren; He, Guangli; Yang, Baocheng; Li, Junjie; Research Technologies
    With the development of clean and renewable energy, hydrogen produced via photoelectrochemical (PEC) water splitting has attracted considerable attention. However, to develop the photoanodes with stable and excellent PEC ability is still a big challenge. In our work, TiO2 nanorods decorated with boron doped g-C3N4 (BCN/TiO2) is fabricated via thermal polymerization method to improve the PEC performance. The BCN/TiO2 displays 4-fold increase of the photocurrent density (1.01 mA cm−2) at 1.23 V vs. RHE under irradiation (100 mW cm−2, AM 1.5 G). And the onset potential of BCN/TiO2 exhibits a negative shift with 100 mV. Attributed to the broad light absorption of BCN and hetero-junction forming between BCN and TiO2, the IPCE value is increased to 87.8% in 380 nm, and the charge separation and transfer efficiency are both increased. Doping metal-free inorganic material with heteroatoms is a simple and efficient strategy to increase the light absorption within visible light and charge transfer efficiency in PEC and photocatalytic applications.
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    Frizzled-7 Identifies Platinum-Tolerant Ovarian Cancer Cells Susceptible to Ferroptosis
    (American Association for Cancer Research, 2021-01-15) Wang, Yinu; Zhao, Guangyuan; Condello, Salvatore; Huang, Hao; Cardenas, Horacio; Tanner, Edward J.; Wei, JianJun; Ji, Yanrong; Li, Junjie; Tan, Yuying; Davuluri, Ramana V.; Peter, Marcus E.; Cheng, Ji-Xin; Matei, Daniela; Obstetrics and Gynecology, School of Medicine
    Defining traits of platinum-tolerant cancer cells could expose new treatment vulnerabilities. Here, new markers associated with platinum-tolerant cells and tumors were identified using in vitro and in vivo ovarian cancer (OC) models treated repetitively with carboplatin and validated in human specimens. Platinum-tolerant cells and tumors were enriched in ALDH(+) cells, formed more spheroids, and expressed increased levels of stemness-related transcription factors compared to parental cells. Additionally, platinum-tolerant cells and tumors exhibited expression of the Wnt receptor Frizzled 7 (FZD7). Knockdown of FZD7 improved sensitivity to platinum, decreased spheroid formation, and delayed tumor initiation. The molecular signature distinguishing FZD7(+) from FZD7(−) cells included epithelial-to-mesenchymal (EMT), stemness, and oxidative phosphorylation-enriched gene sets. Overexpression of FZD7 activated the oncogenic factor Tp63, driving upregulation of glutathione metabolism pathways, including glutathione peroxidase 4 (GPX4), which protected cells from chemotherapy-induced oxidative stress. FZD7(+) platinum-tolerant OC cells were more sensitive and underwent ferroptosis after treatment with GPX4 inhibitors. FZD7, Tp63, and glutathione metabolism gene sets were strongly correlated in the OC Tumor Cancer Genome Atlas (TCGA) database and in residual human OC specimens after chemotherapy. These results support the existence of a platinum-tolerant cell population with partial cancer stem cell features, characterized by FZD7 expression and dependent on FZD7-β-catenin-Tp63-GPX4 pathway for survival. The findings reveal a novel therapeutic vulnerability of platinum-tolerant cancer cells and provide new insight into a potential “persister cancer cell” phenotype.
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    Label-free quantitative imaging of cholesterol in intact tissues by hyperspectral stimulated Raman scattering microscopy
    (Wiley, 2013-12) Wang, Ping; Li, Junjie; Wang, Pu; Hu, Chun-Rui; Zhang, Delong; Sturek, Michael; Cheng, Ji-Xin; Department of Cellular & Integrative Physiology, School of Medicine
    A finger on the pulse: Current molecular analysis of cells and tissues routinely relies on separation, enrichment, and subsequent measurements by various assays. Now, a platform of hyperspectral stimulated Raman scattering microscopy has been developed for the fast, quantitative, and label-free imaging of biomolecules in intact tissues using spectroscopic fingerprints as the contrast mechanism.
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    Lipid Desaturation Is a Metabolic Marker and Therapeutic Target of Ovarian Cancer Stem Cells
    (Elsevier, 2017-03-02) Li, Junjie; Condello, Salvatore; Thomes-Pepin, Jessica; Ma, Xiaoxiao; Xia, Yu; Hurley, Thomas D.; Matei, Daniela; Cheng, Ji-Xin; Obstetrics and Gynecology, School of Medicine
    Lack of sensitive single-cell analysis tools has limited the characterization of metabolic activity in cancer stem cells. By hyperspectral stimulated Raman scattering imaging of single living cells and mass spectrometry analysis of extracted lipids, we report here significantly increased levels of unsaturated lipids in ovarian cancer stem cells (CSCs) as compared to non-CSCs. Higher lipid unsaturation levels were also detected in CSC-enriched spheroids compared to monolayer cultures of ovarian cancer cell lines or primary cells. Inhibition of lipid desaturases effectively eliminated CSCs, suppressed sphere formation in vitro, and blocked tumor initiation capacity in vivo. Mechanistically, we demonstrate that NF-κB directly regulates the expression levels of lipid desaturases and that inhibition of desaturases blocks NF-κB signaling. Collectively, our findings reveal that increased lipid unsaturation is a metabolic marker for ovarian CSCs and a target for CSC-specific therapy.,
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    An Organic–Inorganic Hybrid Cathode Based on S–Se Dynamic Covalent Bonds
    (Wiley, 2020-02) Zhao, Jiawei; Si, Yubing; Han, Zixiao; Li, Junjie; Guo, Wei; Fu, Yongzhu; Medicine, School of Medicine
    A diphenyl trisulfide–selenium nanowire (DPTS‐Se) organic–inorganic hybrid cathode material is presented for rechargeable lithium batteries. During discharge, three voltage plateaus associated with three lithiation processes are observed. During recharge, the combination of the radicals formed upon delithiation leads to several new phenyl sulfoselenide compounds which are confirmed by HPLC‐QTof‐MS. The hybrid cathode exhibits superior cycling stability over pristine Se or DPTS as cathode alone. The first discharge shows a capacity of 96.5 % of the theoretical specific capacity and the cell retains 69.2 % of the initial capacity over 250 cycles. The hybrid cathode also shows a high Coulombic efficiency of over 99 % after 250 cycles. This study demonstrates that the combination of organic polysulfide and selenium can not only improve the utilization of active materials but also enhance the cycling performance.
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    Tau-related white-matter alterations along spatially selective pathways
    (Elsevier, 2021-02-01) Wen, Qiuting; Risacher, Shannon L.; Xie, Linhui; Li, Junjie; Harezlak, Jaroslaw; Farlow, Martin R.; Unverzagt, Frederick W.; Gao, Sujuan; Apostolova, Liana G.; Saykin, Andrew J.; Wu, Yu-Chien; Radiology and Imaging Sciences, School of Medicine
    Progressive accumulation of tau neurofibrillary tangles in the brain is a defining pathologic feature of Alzheimer's disease (AD). Tau pathology exhibits a predictable spatiotemporal spreading pattern, but the underlying mechanisms of this spread are poorly understood. Although AD is conventionally considered a disease of the gray matter, it is also associated with pronounced and progressive deterioration of the white matter (WM). A link between abnormal tau and WM degeneration is suggested by findings from both animal and postmortem studies, but few studies demonstrated their interplay in vivo. Recent advances in diffusion magnetic resonance imaging and the availability of tau positron emission tomography (PET) have made it possible to evaluate the association of tau and WM degeneration (tau-WM) in vivo. In this study, we explored the spatial pattern of tau-WM associations across the whole brain to evaluate the hypothesis that tau deposition is associated with WM microstructural alterations not only in isolated tracts, but in continuous structural connections in a stereotypic pattern. Sixty-two participants, including 22 cognitively normal subjects, 22 individuals with subjective cognitive decline, and 18 with mild cognitive impairment were included in the study. WM characteristics were inferred by classic diffusion tensor imaging (DTI) and a complementary diffusion compartment model - neurite orientation dispersion and density imaging (NODDI) that provides a proxy for axonal density. A data-driven iterative searching (DDIS) approach, coupled with whole-brain graph theory analyses, was developed to continuously track tau-WM association patterns. Without applying prior knowledge of the tau spread, we observed a distinct spatial pattern that resembled the typical propagation of tau pathology in AD. Such association pattern was not observed between diffusion and amyloid-β PET signal. Tau-related WM degeneration is characterized by an increase in the mean diffusivity (with a dominant change in the radial direction) and a decrease in the intra-axonal volume fraction. These findings suggest that cortical tau deposition (as measured in tau PET) is associated with a lower axonal packing density and greater diffusion freedom. In conclusion, our in vivo findings using a data-driven method on cross-sectional data underline the important role of WM alterations in the AD pathological cascade with an association pattern similar to the postmortem Braak staging of AD. Future studies will focus on longitudinal analyses to provide in vivo evidence of tau pathology spreads along neuroanatomically connected brain areas.
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    White matter alterations in early-stage Alzheimer's disease: A tract-specific study
    (Elsevier, 2019-08-21) Wen, Qiuting; Mustafi, Sourajit M.; Li, Junjie; Risacher, Shannon L.; Tallman, Eileen; Brown, Steven A.; West, John D.; Harezlak, Jaroslaw; Farlow, Martin R.; Unverzagt, Frederick W.; Gao, Sujuan; Apostolova, Liana G.; Saykin, Andrew J.; Wu, Yu-Chien; Radiology and Imaging Sciences, School of Medicine
    Introduction: Diffusion magnetic resonance imaging may allow for microscopic characterization of white matter degeneration in early stages of Alzheimer's disease. Methods: Multishell Diffusion magnetic resonance imaging data were acquired from 100 participants (40 cognitively normal, 38 with subjective cognitive decline, and 22 with mild cognitive impairment [MCI]). White matter microscopic degeneration in 27 major tracts of interest was assessed using diffusion tensor imaging (DTI), neurite orientation dispersion and density imaging, and q-space imaging. Results: Lower DTI fractional anisotropy and higher radial diffusivity were observed in the cingulum, thalamic radiation, and forceps major of participants with MCI. These tracts of interest also had the highest predictive power to discriminate groups. Diffusion metrics were associated with cognitive performance, particularly Rey Auditory Verbal Learning Test immediate recall, with the highest association observed in participants with MCI. Discussion: While DTI was the most sensitive, neurite orientation dispersion and density imaging and q-space imaging complementarily characterized reduced axonal density accompanied with dispersed and less restricted white matter microstructures.