IU Indianapolis ScholarWorks :: Browsing by Author "Liu, Jun"

Browsing by Author "Liu, Jun"

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Aberrant epigenetic and transcriptional events associated with breast cancer risk
(BMC, 2022-02-09) Marino, Natascia; German, Rana; Podicheti, Ram; Rusch, Douglas B.; Rockey, Pam; Huang, Jie; Sandusky, George E.; Temm, Constance J.; Althouse, Sandra; Nephew, Kenneth P.; Nakshatri, Harikrishna; Liu, Jun; Vode, Ashley; Cao, Sha; Storniolo, Anna Maria V.; Medicine, School of Medicine
Background: Genome-wide association studies have identified several breast cancer susceptibility loci. However, biomarkers for risk assessment are still missing. Here, we investigated cancer-related molecular changes detected in tissues from women at high risk for breast cancer prior to disease manifestation. Disease-free breast tissue cores donated by healthy women (N = 146, median age = 39 years) were processed for both methylome (MethylCap) and transcriptome (Illumina's HiSeq4000) sequencing. Analysis of tissue microarray and primary breast epithelial cells was used to confirm gene expression dysregulation. Results: Transcriptomic analysis identified 69 differentially expressed genes between women at high and those at average risk of breast cancer (Tyrer-Cuzick model) at FDR < 0.05 and fold change ≥ 2. Majority of the identified genes were involved in DNA damage checkpoint, cell cycle, and cell adhesion. Two genes, FAM83A and NEK2, were overexpressed in tissue sections (FDR < 0.01) and primary epithelial cells (p < 0.05) from high-risk breasts. Moreover, 1698 DNA methylation changes were identified in high-risk breast tissues (FDR < 0.05), partially overlapped with cancer-related signatures, and correlated with transcriptional changes (p < 0.05, r ≤ 0.5). Finally, among the participants, 35 women donated breast biopsies at two time points, and age-related molecular alterations enhanced in high-risk subjects were identified. Conclusions: Normal breast tissue from women at high risk of breast cancer bears molecular aberrations that may contribute to breast cancer susceptibility. This study is the first molecular characterization of the true normal breast tissues, and provides an opportunity to investigate molecular markers of breast cancer risk, which may lead to new preventive approaches.
Early innate and adaptive immune perturbations determine long-term severity of chronic virus and Mycobacterium tuberculosis coinfection
(Elsevier, 2021) Xu, Wenxi; Snell, Laura M.; Guo, Mengdi; Boukhaled, Giselle; Macleod, Bethany L.; Li, Ming; Tullius, Michael V.; Guidos, Cynthia J.; Tsao, Ming-Sound; Divangahi, Maziar; Horwitz, Marcus A.; Liu, Jun; Brooks, David G.; Microbiology and Immunology, School of Medicine
Chronic viral infections increase severity of Mycobacterium tuberculosis (Mtb) coinfection. Here, we examined how chronic viral infections alter the pulmonary microenvironment to foster coinfection and worsen disease severity. We developed a coordinated system of chronic virus and Mtb infection that induced central clinical manifestations of coinfection, including increased Mtb burden, extra-pulmonary dissemination, and heightened mortality. These disease states were not due to chronic virus-induced immunosuppression or exhaustion; rather, increased amounts of the cytokine TNFα initially arrested pulmonary Mtb growth, impeding dendritic cell mediated antigen transportation to the lymph node and subverting immune-surveillance, allowing bacterial sanctuary. The cryptic Mtb replication delayed CD4 T cell priming, redirecting T helper (Th) 1 toward Th17 differentiation and increasing pulmonary neutrophilia, which diminished long-term survival. Temporally restoring CD4 T cell induction overcame these diverse disease sequelae to enhance Mtb control. Thus, Mtb co-opts TNFα from the chronic inflammatory environment to subvert immune-surveillance, avert early immune function, and foster long-term coinfection.
An ensemble of specifically targeted proteins stabilizes cortical microtubules in the human parasite Toxoplasma gondii
(American Society for Cell Biology, 2016-02-01) Liu, Jun; He, Yudou; Benmerzouga, Imaan; Sullivan, William J., Jr.; Morrissette, Naomi S.; Murray, John M.; Hu, Ke; Department of Pharmacology and Toxicology, IU School of Medicine
Although all microtubules within a single cell are polymerized from virtually identical subunits, different microtubule populations carry out specialized and diverse functions, including directional transport, force generation, and cellular morphogenesis. Functional differentiation requires specific targeting of associated proteins to subsets or even subregions of these polymers. The cytoskeleton of Toxoplasma gondii, an important human parasite, contains at least five distinct tubulin-based structures. In this work, we define the differential localization of proteins along the cortical microtubules of T. gondii, established during daughter biogenesis and regulated by protein expression and exchange. These proteins distinguish cortical from mitotic spindle microtubules, even though the assembly of these subsets is contemporaneous during cell division. Finally, proteins associated with cortical microtubules collectively protect the stability of the polymers with a remarkable degree of functional redundancy.
Ex vivo Dynamics of Human Glioblastoma Cells in a Microvasculature-on-a-Chip System Correlates with Tumor Heterogeneity and Subtypes
(Wiley, 2019-02-10) Xiao, Yang; Kim, Dongjoo; Dura, Burak; Zhang, Kerou; Yan, Runchen; Li, Huamin; Han, Edward; Ip, Joshua; Zou, Pan; Liu, Jun; Chen, Ann Tai; Vortmeyer, Alexander O.; Zhou, Jiangbing; Fan, Rong; Pathology and Laboratory Medicine, School of Medicine
The perivascular niche (PVN) plays an essential role in brain tumor stem-like cell (BTSC) fate control, tumor invasion, and therapeutic resistance. Here, a microvasculature-on-a-chip system as a PVN model is used to evaluate the ex vivo dynamics of BTSCs from ten glioblastoma patients. BTSCs are found to preferentially localize in the perivascular zone, where they exhibit either the lowest motility, as in quiescent cells, or the highest motility, as in the invasive phenotype, with migration over long distance. These results indicate that PVN is a niche for BTSCs, while the microvascular tracks may serve as a path for tumor cell migration. The degree of colocalization between tumor cells and microvessels varies significantly across patients. To validate these results, single-cell transcriptome sequencing (10 patients and 21 750 single cells in total) is performed to identify tumor cell subtypes. The colocalization coefficient is found to positively correlate with proneural (stem-like) or mesenchymal (invasive) but not classical (proliferative) tumor cells. Furthermore, a gene signature profile including PDGFRA correlates strongly with the “homing” of tumor cells to the PVN. These findings demonstrate that the model can recapitulate in vivo tumor cell dynamics and heterogeneity, representing a new route to study patient-specific tumor cell functions.
Interaction between Schwann cells and other cells during repair of peripheral nerve injury
(Wolters Kluwer, 2021-01) Qu, Wen-Rui; Zhu, Zhe; Liu, Jun; Song, De-Biao; Tian, Heng; Chen, Bing-Peng; Li, Rui; Deng, Ling-Xiao; Neurological Surgery, School of Medicine
Peripheral nerve injury (PNI) is common and, unlike damage to the central nervous system injured nerves can effectively regenerate depending on the location and severity of injury. Peripheral myelinating glia, Schwann cells (SCs), interact with various cells in and around the injury site and are important for debris elimination, repair, and nerve regeneration. Following PNI, Wallerian degeneration of the distal stump is rapidly initiated by degeneration of damaged axons followed by morphologic changes in SCs and the recruitment of circulating macrophages. Interaction with fibroblasts from the injured nerve microenvironment also plays a role in nerve repair. The replication and migration of injury-induced dedifferentiated SCs are also important in repairing the nerve. In particular, SC migration stimulates axonal regeneration and subsequent myelination of regenerated nerve fibers. This mobility increases SC interactions with other cells in the nerve and the exogenous environment, which influence SC behavior post-injury. Following PNI, SCs directly and indirectly interact with other SCs, fibroblasts, and macrophages. In addition, the inter- and intracellular mechanisms that underlie morphological and functional changes in SCs following PNI still require further research to explain known phenomena and less understood cell-specific roles in the repair of the injured peripheral nerve. This review provides a basic assessment of SC function post-PNI, as well as a more comprehensive evaluation of the literature concerning the SC interactions with macrophages and fibroblasts that can influence SC behavior and, ultimately, repair of the injured nerve.
Interplay of Metabolome and Gut Microbiome in Individuals With Major Depressive Disorder vs Control Individuals
(American Medical Association, 2023) Amin, Najaf; Liu, Jun; Bonnechere, Bruno; MahmoudianDehkordi, Siamak; Arnold, Matthias; Batra, Richa; Chiou, Yu-Jie; Fernandes, Marco; Ikram, M. Arfan; Kraaij, Robert; Krumsiek, Jan; Newby, Danielle; Nho, Kwangsik; Radjabzadeh, Djawad; Saykin, Andrew J.; Shi, Liu; Sproviero, William; Winchester, Laura; Yang, Yang; Nevado-Holgado, Alejo J.; Kastenmüller, Gabi; Kaddurah-Daouk, Rima; van Duijn, Cornelia M.; Radiology and Imaging Sciences, School of Medicine
Importance: Metabolomics reflect the net effect of genetic and environmental influences and thus provide a comprehensive approach to evaluating the pathogenesis of complex diseases, such as depression. Objective: To identify the metabolic signatures of major depressive disorder (MDD), elucidate the direction of associations using mendelian randomization, and evaluate the interplay of the human gut microbiome and metabolome in the development of MDD. Design, setting and participants: This cohort study used data from participants in the UK Biobank cohort (n = 500 000; aged 37 to 73 years; recruited from 2006 to 2010) whose blood was profiled for metabolomics. Replication was sought in the PREDICT and BBMRI-NL studies. Publicly available summary statistics from a 2019 genome-wide association study of depression were used for the mendelian randomization (individuals with MDD = 59 851; control individuals = 113 154). Summary statistics for the metabolites were obtained from OpenGWAS in MRbase (n = 118 000). To evaluate the interplay of the metabolome and the gut microbiome in the pathogenesis of depression, metabolic signatures of the gut microbiome were obtained from a 2019 study performed in Dutch cohorts. Data were analyzed from March to December 2021. Main outcomes and measures: Outcomes were lifetime and recurrent MDD, with 249 metabolites profiled with nuclear magnetic resonance spectroscopy with the Nightingale platform. Results: The study included 6811 individuals with lifetime MDD compared with 51 446 control individuals and 4370 individuals with recurrent MDD compared with 62 508 control individuals. Individuals with lifetime MDD were younger (median [IQR] age, 56 [49-62] years vs 58 [51-64] years) and more often female (4447 [65%] vs 2364 [35%]) than control individuals. Metabolic signatures of MDD consisted of 124 metabolites spanning the energy and lipid metabolism pathways. Novel findings included 49 metabolites, including those involved in the tricarboxylic acid cycle (ie, citrate and pyruvate). Citrate was significantly decreased (β [SE], -0.07 [0.02]; FDR = 4 × 10-04) and pyruvate was significantly increased (β [SE], 0.04 [0.02]; FDR = 0.02) in individuals with MDD. Changes observed in these metabolites, particularly lipoproteins, were consistent with the differential composition of gut microbiota belonging to the order Clostridiales and the phyla Proteobacteria/Pseudomonadota and Bacteroidetes/Bacteroidota. Mendelian randomization suggested that fatty acids and intermediate and very large density lipoproteins changed in association with the disease process but high-density lipoproteins and the metabolites in the tricarboxylic acid cycle did not. Conclusions and relevance: The study findings showed that energy metabolism was disturbed in individuals with MDD and that the interplay of the gut microbiome and blood metabolome may play a role in lipid metabolism in individuals with MDD.
Probiotic and Oxytocin Combination Therapy in Patients with Autism Spectrum Disorder: A Randomized, Double-Blinded, Placebo-Controlled Pilot Trial
(MDPI, 2021-05-05) Kong, Xue-Jun; Liu, Jun; Liu, Kevin; Koh, Madelyn; Sherman, Hannah; Liu, Siyu; Tian, Ruiyi; Sukijthamapan, Piyawat; Wang, Jiuju; Fong, Michelle; Xu, Lei; Clairmont, Cullen; Jeong, Min-Seo; Li, Alice; Lopes, Maria; Hagan, Veronica; Dutton, Tess; Chan, Suk-Tak (Phoebe); Lee, Hang; Kendall, Amy; Kwong, Kenneth; Song, Yiqing; Epidemiology, School of Public Health
Autism spectrum disorder (ASD) is a rapidly growing neurodevelopmental disorder. Both probiotics and oxytocin were reported to have therapeutic potential; however, the combination therapy has not yet been studied. We conducted a randomized, double-blinded, placebo-controlled, 2-stage pilot trial in 35 individuals with ASD aged 3-20 years (median = 10.30 years). Subjects were randomly assigned to receive daily Lactobacillus plantarum PS128 probiotic (6 × 1010 CFUs) or a placebo for 28 weeks; starting on week 16, both groups received oxytocin. The primary outcomes measure socio-behavioral severity using the Social Responsiveness Scale (SRS) and Aberrant Behavior Checklist (ABC). The secondary outcomes include measures of the Clinical Global Impression (CGI) scale, fecal microbiome, blood serum inflammatory markers, and oxytocin. All outcomes were compared between the two groups at baseline, 16 weeks, and 28 weeks into treatment. We observed improvements in ABC and SRS scores and significant improvements in CGI-improvement between those receiving probiotics and oxytocin combination therapy compared to those receiving placebo (p < 0.05). A significant number of favorable gut microbiome network hubs were also identified after combination therapy (p < 0.05). The favorable social cognition response of the combination regimen is highly correlated with the abundance of the Eubacterium hallii group. Our findings suggest synergic effects between probiotics PS128 and oxytocin in ASD patients, although further investigation is warranted.
Probiotic Therapy for Treating Behavioral and Gastrointestinal Symptoms in Autism Spectrum Disorder: A Systematic Review of Clinical Trials
(Springer, 2019) Liu, Jun; Wan, Guo-bing; Huang, Ming-shi; Agyapong, George; Zou, Tian-le; Zhang, Xue-ying; Liu, Yen-Wenn; Song, Yi-qing; Tsai, Ying-Chieh; Kong, Xue-jun; Epidemiology, School of Public Health
The therapeutic potentials of probiotics in autism spectrum disorder (ASD) remains controversial, with the only existing systematic review on this topic published in 2015. Results from new trials have become available in recent years. We therefore conducted an updated systematic review, to assess the efficacy of probiotics in relieving behavioral symptoms of ASD and gastrointestinal comorbidities. Our review includes two randomized controlled trials, which showed improvement of ASD behaviors, and three open trials, all which exhibited a trend of improvement. Four of these trials concluded from subjective measures that gastrointestinal function indices showed a trend of improvement with probiotic therapy. Additional rigorous trials are needed to evaluate the effects of probiotic supplements in ASD.
RUSSIA AND CHINA IN TRANSITION: IMPLICATIONS FOR HRD RESEARCH AND PRACTICE IN GLOBAL COMMUNITY
(2005-10-13T19:38:17Z) Liu, Jun; Niemi, John
In recent years, both Russia and China have attempted to move toward a market economy from a centralized, tightly controlled economic and political system that had held sway for many decades. In Russia, the attempt foundered largely because Russia moved too quickly without giving sufficient attention to its history and tradition. China, on the other hand, has retained elements of a centralized system while moving gradually toward a market economy. Both countries had had numbers of state-owned enterprises (SOEs) that became the key element of and central to the economic transition. Lewin's model of force-field analysis is used as a means to analyze the forces that both drive and restrain the economic restructuring. Entry into World Trade Organization (WTO) challenges both countries' SOEs. Training SOEs leaders to obtain core competencies is a crucial first step for SOEs to survive and develop in a global marketplace.

Browsing by Author "Liu, Jun"

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