Browsing by Author "Zhang, Yue"
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Item Anxiety Trajectories the First 10 Years After a Traumatic Brain Injury (TBI): A TBI Model Systems Study(Elsevier, 2022-11) Neumann, Dawn; Juengst, Shannon B.; Bombardier, Charles H.; Finn, Jacob A.; Miles, Shannon R.; Zhang, Yue; Kennedy, Richard; Rabinowitz, Amanda R.; Thomas, Amber; Dreer, Laura E.; Physical Medicine and Rehabilitation, School of MedicineObjective Determine anxiety trajectories and predictors up to 10 years posttraumatic brain injury (TBI). Design Prospective longitudinal, observational study. Setting Inpatient rehabilitation centers. Participants 2836 participants with moderate to severe TBI enrolled in the TBI Model Systems National Database who had ≥2 anxiety data collection points (N=2836). Main Outcome Measure Generalized Anxiety Disorder-7 (GAD-7) at 1, 2, 5, and 10-year follow-ups. Results Linear mixed models showed higher GAD-7 scores were associated with Black race (P<.001), public insurance (P<.001), pre-injury mental health treatment (P<.001), 2 additional TBIs with loss of consciousness (P=.003), violent injury (P=.047), and more years post-TBI (P=.023). An interaction between follow-up year and age was also related to GAD-7 scores (P=.006). A latent class mixed model identified 3 anxiety trajectories: low-stable (n=2195), high-increasing (n=289), and high-decreasing (n=352). The high-increasing and high-decreasing groups had mild or higher GAD-7 scores up to 10 years. Compared to the low-stable group, the high-decreasing group was more likely to be Black (OR=2.25), have public insurance (OR=2.13), have had pre-injury mental health treatment (OR=1.77), and have had 2 prior TBIs (OR=3.16). Conclusions A substantial minority of participants had anxiety symptoms that either increased (10%) or decreased (13%) over 10 years but never decreased below mild anxiety. Risk factors of anxiety included indicators of socioeconomic disadvantage (public insurance) and racial inequities (Black race) as well as having had pre-injury mental health treatment and 2 prior TBIs. Awareness of these risk factors may lead to identifying and proactively referring susceptible individuals to mental health services.Item Correction: γδ T cell IFNγ production is directly subverted by Yersinia pseudotuberculosis outer protein YopJ in mice and humans(Public Library of Science, 2022-05-25) Chu, Timothy H.; Khairallah, Camille; Shieh, Jason; Cho, Rhea; Qiu, Zhijuan; Zhang, Yue; Eskiocak, Onur; Thanassi, David G.; Kaplan, Mark H.; Beyaz, Semir; Yang, Vincent W.; Bliska, James B.; Sheridan, Brian S.; Microbiology and Immunology, School of MedicineThis corrects the article "γδ T cell IFNγ production is directly subverted by Yersinia pseudotuberculosis outer protein YopJ in mice and humans" in volume 17, e1010103.Item Epalrestat Stimulated Oxidative Stress, Inflammation, and Fibrogenesis in Mouse Liver(Oxford University Press, 2018) Le, Yuan; Chen, Liming; Zhang, Yue; Bu, Pengli; Dai, Guoli; Cheng, Xingguo; Biology, School of ScienceEpalrestat (EPS), an aldose reductase inhibitor, is widely prescribed to manage diabetic neuropathy. It is generally believed that EPS is beneficial to diabetic patients because it can protect endothelial cells, Schwann cells, or other neural cells from oxidative stress. However, several clinical studies revealed that EPS therapy led to liver dysfunction, which limited its clinical applications. Currently, the underlying mechanism by which EPS causes liver dysfunction is unknown. This study aimed to investigate the mechanism responsible for EPS-induced liver injury. In mouse liver, EPS 1) increased oxidative stress, indicated by increased expression of manganese superoxide dismutase, Ho-1, and Nqo1, 2) induced inflammation, indicated by infiltration of inflammatory cells, and induced expression of tumor necrosis factor-alpha, CD11b, and CD11c, as well as 3) predisposed to induce fibrosis, evidenced by increased mRNA and protein expression of early profibrotic biomarker genes procollagen I and alpha-smooth muscle actin, and by increased collagen deposition. In cultured mouse and human hepatoma cells, EPS treatment induced oxidative stress, decreased cell viability, and triggered apoptosis evidenced by increased Caspase-3 cleavage/activation. In addition, EPS increased mRNA and protein expression of cytoglobin in mouse liver, indicating that EPS activated hepatic stellate cells (HSCs). Furthermore, EPS treatment in cultured human HSCs increased cell viability. In summary, EPS administration induced oxidative stress and inflammation in mouse liver, and stimulated liver fibrogenesis. Therefore, cautions should be exercised during EPS therapy.Item IGF-1R modulation of acute GH-induced STAT5 signaling: role of protein tyrosine phosphatase activity(Endocrine Society, 2013-11) Gan, Yujun; Zhang, Yue; Buckels, Ashiya; Paterson, Andrew J.; Jiang, Jing; Clemens, Thomas L.; Zhang, Zhong-Yin; Du, Keyong; Chang, Yingzi; Frank, Stuart J.; Biochemistry & Molecular Biology, School of MedicineGH is a potent anabolic and metabolic factor that binds its cell surface receptor (GHR), activating the GHR-associated tyrosine kinase, Janus kinase 2, which phosphorylates and activates the latent transcription factor, signal transducer and activator of transcription 5 (STAT5). Some GH actions are mediated by the elaboration of IGF-1, which exerts effects by binding and activating the heterotetrameric tyrosine kinase growth factor receptor, IGF-1R. In addition to this GH-GHR-IGF-1-IGF-1R scheme, we have demonstrated in primary osteoblasts and in islet β-cells that then deletion or silencing of IGF-1R results in diminished GH-induced STAT5 phosphorylation, suggesting that the presence of IGF-1R may facilitate GH signaling. In this study, we explore potential roles for protein tyrosine phosphatase activity in modulating GH-induced signaling, comparing conditions in which IGF-1R is present or diminished. We confirm that in mouse primary osteoblasts harboring loxP sites flanking the IGF-1R gene, infection with an adenovirus that expresses the Cre recombinase results in IGF-1R deletion and diminished acute GH-induced STAT5 phosphorylation. Furthermore, we present a new model of IGF-1R silencing, in which expression of short hairpin RNA directed at IGF-1R greatly reduces IGF-1R abundance in LNCaP human prostate cancer cells. In both models, treatment with a chemical inhibitor of protein tyrosine phosphatase-1B (PTP-1B), but not one of src homology region 2 domain-containing phosphotase-1 (SHP-1) and SHP-2, reverses the loss of GH-induced STAT5 phosphorylation in cells lacking IGF-1R but has no effect in cells with intact IGF-1R. Furthermore, expression of either a dominant-negative PTP-1B or the PTP-1B-interacting inhibitory protein, constitutive photomorphogenesis 1, also rescues acute GH-induced STAT5 signaling in IGF-1R-deficient cells but has no effect in IGF-1R replete cells. By expressing a substrate-trapping mutant PTP-1B, we demonstrate that tyrosine phosphorylated Janus kinase-2 is a PTP-1B substrate only in cells lacking IGF-1R. Collectively, our data suggest that IGF-1R positively regulates acute GH signaling by preventing access of PTP-1B activity to Janus kinase 2 and thereby preventing PTP-1B-mediated suppression of GH-induced STAT5 activation.Item MiR-373 targeting of the Rab22a oncogene suppresses tumor invasion and metastasis in ovarian cancer(Impact Journals, 2014-12-15) Zhang, Yue; Zhao, Fu-Jun; Chen, Li-Lan; Wang, Luo-Qiao; Nephew, Kenneth P.; Wu, Ying-Li; Zhang, Shu; Department of Medicine, IU School of MedicineMetastasis is major cause of mortality in patients with ovarian cancer. MiR-373 has been shown to play pivotal roles in tumorigenesis and metastasis; however, a role for miR-373 in ovarian cancer has not been investigated. In this study, we show that the miR-373 expression is down-regulated in human epithelial ovarian cancer (EOC) and inversely correlated with clinical stage and histological grade. Ectopic overexpression of miR-373 in human EOC cells suppressed cell invasion in vitro and metastasis in vivo, and the epithelial-mesenchymal transition process. Silencing the expression of miR-373 resulted in an increased migration and invasion of EOC cells. Using integrated bioinformatics analysis, gene expression arrays, and luciferase assay, we identified Rab22a as a direct and functional target of miR-373 in EOC cells. Expression levels of miR-373 were inversely correlated with Rab22a protein levels in human EOC tissues. Rab22a knockdown inhibited invasion and migration of EOC cells, increased E-cadherin expression, and suppressed the expression of N-cadherin. Moreover, overexpression of Rab22a abrogated miR-373-induced invasion and migration of EOC cells. Taken together, these results demonstrate that miR-373 suppresses EOC invasion and metastasis by directly targeting Rab22a gene, a new potential therapeutic target in EOC.Item MMP-3 mediates copper oxide nanoparticle-induced pulmonary inflammation and fibrosis(Springer Nature, 2024-07-19) Zhang, Yuanbao; Zhang, Zhenyu; Mo, Yiqun; Zhang, Yue; Yuan, Jiali; Zhang, Qunwei; Epidemiology, Richard M. Fairbanks School of Public HealthBackground: The increasing production and usage of copper oxide nanoparticles (Nano-CuO) raise human health concerns. Previous studies have demonstrated that exposure to Nano-CuO could induce lung inflammation, injury, and fibrosis. However, the potential underlying mechanisms are still unclear. Here, we proposed that matrix metalloproteinase-3 (MMP-3) might play an important role in Nano-CuO-induced lung inflammation, injury, and fibrosis. Results: Exposure of mice to Nano-CuO caused acute lung inflammation and injury in a dose-dependent manner, which was reflected by increased total cell number, neutrophil count, macrophage count, lactate dehydrogenase (LDH) activity, and CXCL1/KC level in bronchoalveolar lavage fluid (BALF) obtained on day 3 post-exposure. The time-response study showed that Nano-CuO-induced acute lung inflammation and injury appeared as early as day 1 after exposure, peaked on day 3, and ameliorated over time. However, even on day 42 post-exposure, the LDH activity and macrophage count were still higher than those in the control group, suggesting that Nano-CuO caused chronic lung inflammation. The Nano-CuO-induced pulmonary inflammation was further confirmed by H&E staining of lung sections. Trichrome staining showed that Nano-CuO exposure caused pulmonary fibrosis from day 14 to day 42 post-exposure with an increasing tendency over time. Increased hydroxyproline content and expression levels of fibrosis-associated proteins in mouse lungs were also observed. In addition, Nano-CuO exposure induced MMP-3 overexpression and increased MMP-3 secretion in mouse lungs. Knocking down MMP-3 in mouse lungs significantly attenuated Nano-CuO-induced acute and chronic lung inflammation and fibrosis. Moreover, Nano-CuO exposure caused sustained production of cleaved osteopontin (OPN) in mouse lungs, which was also significantly decreased by knocking down MMP-3. Conclusions: Our results demonstrated that short-term Nano-CuO exposure caused acute lung inflammation and injury, while long-term exposure induced chronic pulmonary inflammation and fibrosis. Knocking down MMP-3 significantly ameliorated Nano-CuO-induced pulmonary inflammation, injury, and fibrosis, and also attenuated Nano-CuO-induced cleaved OPN level. Our study suggests that MMP-3 may play important roles in Nano-CuO-induced pulmonary inflammation and fibrosis via cleavage of OPN and may provide a further understanding of the mechanisms underlying Nano-CuO-induced pulmonary toxicity.Item Recycled two-stage estimation in nonlinear mixed effects regression models(Springer, 2022-09) Zhang, Yue; Boukai, Ben; Mathematical Sciences, School of ScienceWe consider a re-sampling scheme for estimation of the population parameters in the mixed-effects nonlinear regression models of the type used, for example, in clinical pharmacokinetics. We provide a two-stage estimation procedure which resamples (or recycles), via random weightings, the various parameter's estimates to construct consistent estimates of their respective sampling distributions. In particular, we establish under rather general distribution-free assumptions, the asymptotic normality and consistency of the standard two-stage estimates and of their resampled version and demonstrate the applicability of our proposed resampling methodology in a small simulation study. A detailed example based on real clinical pharmacokinetic data is also provided.Item γδ T cell IFNγ production is directly subverted by Yersinia pseudotuberculosis outer protein YopJ in mice and humans(Public Library of Science, 2021-12-06) Chu, Timothy H.; Khairallah, Camille; Shieh, Jason; Cho, Rhea; Qiu, Zhijuan; Zhang, Yue; Eskiocak, Onur; Thanassi, David G.; Kaplan, Mark H.; Beyaz, Semir; Yang, Vincent W.; Bliska, James B.; Sheridan, Brian S.; Microbiology and Immunology, School of MedicineYersinia pseudotuberculosis is a foodborne pathogen that subverts immune function by translocation of Yersinia outer protein (Yop) effectors into host cells. As adaptive γδ T cells protect the intestinal mucosa from pathogen invasion, we assessed whether Y. pseudotuberculosis subverts these cells in mice and humans. Tracking Yop translocation revealed that the preferential delivery of Yop effectors directly into murine Vγ4 and human Vδ2+ T cells inhibited anti-microbial IFNγ production. Subversion was mediated by the adhesin YadA, injectisome component YopB, and translocated YopJ effector. A broad anti-pathogen gene signature and STAT4 phosphorylation levels were inhibited by translocated YopJ. Thus, Y. pseudotuberculosis attachment and translocation of YopJ directly into adaptive γδ T cells is a major mechanism of immune subversion in mice and humans. This study uncovered a conserved Y. pseudotuberculosis pathway that subverts adaptive γδ T cell function to promote pathogenicity.