Xiaoxuan Fan

University of Maryland, Baltimore

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Steven R. Houser

Temple University

Hajime Kubo

Temple University

Remus M. Berretta

Temple University

William D. Cornwell

Canadian Respiratory Research Network

Thomas J. Rogers

Van Andel Institute

Shan He

Huazhong University of Science and Technology

Ran Reshef

Columbia University Irving Medical Center

Changwei Zhao

Henan University of Science and Technology

Jian Wang

Southern Medical University

Kazuhiro Mochizuki

Fukushima Medical University Hospital

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Temple University

Temple University Hospital

Philadelphia University

Temple College

University of Pennsylvania

Pennsylvania State University

Thomas Jefferson University

Cardiovascular Research Center

University of Nebraska Medical Center

University of Maryland, Baltimore

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Activation and polarization of circulating monocytes in severe chronic obstructive pulmonary disease

BMC Pulmonary Medicine (2018)

William D. Cornwell Victor Kim Xiaoxuan Fan Marie Elena Vega Frederick V. Ramsey

The ability of circulating monocytes to develop into lung macrophages and promote lung tissue damage depends upon their phenotypic pattern of differentiation and activation. Whether this phenotypic pattern varies with COPD severity is unknown. Here we characterize the activation and differentiation status of circulating monocytes in patients with moderate vs. severe COPD.Blood monocytes were isolated from normal non-smokers (14), current smokers (13), patients with moderate (9), and severe COPD (11). These cells were subjected to analysis by flow cytometry to characterize the expression of activation markers, chemoattractant receptors, and surface markers characteristic of either M1- or M2-type macrophages.Patients with severe COPD had increased numbers of total circulating monocytes and non-classical patrolling monocytes, compared to normal subjects and patients with moderate COPD. In addition, while the percentage of circulating monocytes that expressed an M2-like phenotype was reduced in patients with either moderate or severe disease, the levels of expression of M2 markers on this subpopulation of monocytes in severe COPD was significantly elevated. This was particularly evident for the expression of the chemoattractant receptor CCR5.Blood monocytes in severe COPD patients undergo unexpected pre-differentiation that is largely characteristic of M2-macrophage polarization, leading to the emergence of an unusual M2-like monocyte population with very high levels of CCR5. These results show that circulating monocytes in patients with severe COPD possess a cellular phenotype which may permit greater mobilization to the lung, with a pre-existing bias toward a potentially destructive inflammatory phenotype.

Monocyte

10.1186/s12890-018-0664-y

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Citations (43)

The Notch Ligand DLL4 Defines a Capability of Human Dendritic Cells in Regulating Th1 and Th17 Differentiation

The Journal of Immunology (2015)

Lijun Meng Zhenjiang Bai Shan He Kazuhiro Mochizuki Yongnian Liu

Notch signaling regulates multiple helper CD4(+) T cell programs. We have recently demonstrated that dendritic cells (DCs) expressing the Notch ligand DLL4 are critical for eliciting alloreactive T cell responses and induction of graft-versus-host disease in mice. However, the human counterpart of murine DLL4(+) DCs has yet to be examined. We report the identification of human DLL4(+) DCs and their critical role in regulating Th1 and Th17 differentiation. CD1c(+) DCs and plasmacytoid DCs (pDCs) from the peripheral blood (PB) of healthy donors did not express DLL4. In contrast, patients undergoing allogeneic hematopoietic stem cell transplantation had a 16-fold more DLL4(+)CD1c(+) DCs than healthy donors. Upon activation of TLR signaling, healthy donor-derived CD1c(+) DCs dramatically upregulated DLL4, as did pDCs to a lesser extent. Activated DLL4(+) DCs were better able to promote Th1 and Th17 differentiation than unstimulated PB DCs. Blocking DLL4 using a neutralizing Ab decreased Notch signaling in T cells stimulated with DLL4(+) DCs, and it reduced the generation of Th1 and Th17 cells. Both NF-κB and STAT3 were crucial for inducing DLL4 in human DCs. Interestingly, STAT3 directly activated DLL4 transcription and inhibiting STAT3 alone was sufficient to reduce DLL4 in activated PB DCs. Thus, DLL4 is a unique functional molecule of human circulating DCs critical for directing Th1 and Th17 differentiation. These findings identify a pathway for therapeutic intervention for inflammatory disorders in humans, such as graft-versus-host disease after allogeneic hematopoietic stem cell transplantation, autoimmunity, and tumor immunity.

Follicular dendritic cells

10.4049/jimmunol.1501310

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Effects of Moderate Aerobic Exercise Training on Vascular Health and Blood Pressure in African Americans

Journal of Clinical Hypertension (2014)

Deborah L. Feairheller Keith M. Diaz Mohammed A. Kashem Sunny R. Thakkar Praveen Veerabhadrappa

As healthcare progresses toward individualized medicine, understanding how different racial groups respond to lifestyle interventions is valuable. It is established that A frican A mericans have disproportionate levels of cardiovascular disease and impaired vascular health, and clinical practice guidelines suggest lifestyle interventions as the first line of treatment. Recently, the authors reported that 6 months of aerobic exercise improved inflammatory markers, flow‐mediated dilation ( FMD ), and levels of circulating endothelial microparticles ( EMP s) in A frican A merican adults. This study is a subgroup analysis of the aerobic exercise–induced changes in vascular health and blood pressure ( BP ) measures, including carotid artery intima‐media thickness ( IMT ), nitroglycerin‐mediated dilation ( NMD ), ambulatory BP , and office BP . Sedentary A frican A merican adults (53.4±6.2 years; 21 women and 5 men) showed improved vascular health but no change in BP . Carotid artery IMT decreased 6.4%, plasma nitric oxide levels increased 76.6%, plasma EMP levels decreased, percentage of FMD increased 59.6%, and FMD / NMD ratio increased 36.2% ( P <.05 for all). Six months of aerobic exercise training is sufficient to elicit improvements in vascular structure and function in A frican A mericans, even without improvements in BP measures or NMD (ie, smooth muscle function). To our knowledge, this is the first study to report such findings in A frican A mericans.

Aerobic Exercise

10.1111/jch.12328

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Citations (39)

VlincRNAs controlled by retroviral elements are a hallmark of pluripotency and cancer

Genome biology (2013)

Georges St. Laurent Dmitry Shtokalo Biao Dong Michael Tackett Xiaoxuan Fan

Abstract Background The function of the non-coding portion of the human genome remains one of the most important questions of our time. Its vast complexity is exemplified by the recent identification of an unusual and notable component of the transcriptome - very long intergenic non-coding RNAs, termed vlincRNAs. Results Here we identify 2,147 vlincRNAs covering 10 percent of our genome. We show they are present not only in cancerous cells, but also in primary cells and normal human tissues, and are controlled by canonical promoters. Furthermore, vlincRNA promoters frequently originate from within endogenous retroviral sequences. Strikingly, the number of vlincRNAs expressed from endogenous retroviral promoters strongly correlates with pluripotency or the degree of malignant transformation. These results suggest a previously unknown connection between the pluripotent state and cancer via retroviral repeat-driven expression of vlincRNAs. Finally, we show that vlincRNAs can be syntenically conserved in humans and mouse and their depletion using RNAi can cause apoptosis in cancerous cells. Conclusions These intriguing observations suggest that vlincRNAs could create a framework that combines many existing short ESTs and lincRNAs into a landscape of very long transcripts functioning in the regulation of gene expression in the nucleus. Certain types of vlincRNAs participate at specific stages of normal development and, based on analysis of a limited set of cancerous and primary cell lines, they appear to be co-opted by cancer-associated transcriptional programs. This provides additional understanding of transcriptome regulation during the malignant state, and could lead to additional targets and options for its reversal.

Human genetics

Genome Biology

10.1186/gb-2013-14-7-r73

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Citations (86)

Imaging macrophages in trehalose with SIMS

Applied Surface Science (2008)

Shawn Parry Michael E. Kurczy Xiaoxuan Fan Margaret S. Halleck Robert Schlegel

Phosphocholine

10.1016/j.apsusc.2008.05.251

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Abstract 18996: Exosomes Derived From Cortical Bone Stem Cells Are a Novel Cardioprotective Therapy < Myocardial Injury

Circulation (2016)

Sadia Mohsin Constantine D. Troupes Deborah Eaton Mohsin Khan Xiaoxuan Fan

Rationale: Cortical bone derived stem cells (CBSCs) have gained prominence recently due to their incredible growth kinetics and myocardial repair properties that outperform known stem cell types used for cardiac repair. Salutary effects of CBSCs in large are mediated by paracrine secretion. Since exosomes represent active component of released factors whether CBSC derived exosomes (CBSCs-Exo) are a viable therapy for heart repair after injury is presently unknown. Objective: Determine the therapeutic value of CBSC exosomes and their contents for myocardial repair. Methods and Results: Exosomes isolated from murine CBSCs by ultracentrifugation showed typical exosome size (30-100nm) validated by electron microscopy and dynamic light scattering. To determine cardiac therapeutic value, CBSC exosomes (60μg) injected mice after myocardial infarction (MI) demonstrated reduced infarct size and increased myocyte protection after acute MI injury. Interestingly, serum levels of pro-inflammatory cytokines were significantly reduced along with decreased expression of CD68+ cells in animals receiving CBSCs-Exo versus control animals. Long term analysis of CBSC-Exo animals showed improved cardiac function and contractility compared to saline treated animals concurrent with enhanced angiogenesis 6 weeks after MI. Salutary effects of CBSC-Exo were confirmed in vitro and showed increased cardiac protection in NRVMs after hypoxic challenge and enhanced tube formation in HUVECs. Simultaneously, treatment of bone marrow-derived macrophages stimulated with lipopolysaccharide (LPS) and treated with CBSCs-Exo showed increased polarization towards M2 phenotype demonstrating immunomodulation capacity of CBSC-Exo. The underlying mechanism for beneficial effects was tied to increased packaging of cardioprotective miRs in CBSCs-Exo confirmed by MiRNA array analysis. Conclusion: Exosomes derived from CBSCs provide a cell free system using reparative power of CBSC to augment cardiac function after myocardial injury recapitulating earlier findings with CBSCs. Increased packaging of cardioprotective and immune-modulatory miRs highlight a potential new insight into the salutary effects of exosome therapy.

Exosome

Stem Cell Therapy

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T-type Ca2+ channels regulate the exit of cardiac myocytes from the cell cycle after birth

Journal of Molecular and Cellular Cardiology (2013)

Fang Wang Hui Gao Hajime Kubo Xiaoxuan Fan Hongyu Zhang

T-type Ca2+ channels (TTCCs) are expressed in the fetal heart and then disappear from ventricular myocytes after birth. The hypothesis examined in this study was the α1G TTCCs' influence in myocyte maturation and their rapid withdrawal from the cell cycle after birth.MethodsCardiac myocytes were isolated from neonatal and adult wild type (WT), α1G−/− and α1G over expressing (α1GDT) mice. Bromodeoxyuridine (BrdU) uptake, myocyte nucleation, cell cycle analysis, and T-type Ca2+ currents were measured.ResultsAll myocytes were mono-nucleated at birth and 35% of WT myocytes expressed functional TTCCs. Very few neonatal myocytes had functional TTCCs in α1G−/− hearts. By the end of the first week after birth no WT or α1G−/− had functional TTCCs. During the first week after birth about 25% of WT myocytes were BrdU+ and became bi-nucleated. Significantly fewer α1G−/− myocytes became bi-nucleated and fewer of these myocytes were BrdU+. Neonatal α1G−/− myocytes were also smaller than WT. Adult WT and α1G−/− hearts were similar in size, but α1G−/− myocytes were smaller and a greater % were mono-nucleated. α1G over expressing hearts were smaller than WT but their myocytes were larger.ConclusionsThe studies performed show that loss of functional TTCCs is associated with bi-nucleation and myocyte withdrawal from the cell cycle. Loss of α1G TTCCs slowed the transition from mono- to bi-nucleation and resulted in an adult heart with a greater number of small cardiac myocytes. These results suggest that TTCCs are involved in the regulation of myocyte size and the exit of myocytes from the cell cycle during the first week after birth.

Cardiac myocyte

Bromodeoxyuridine

10.1016/j.yjmcc.2013.05.016

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PT-Tuning: Bridging the Gap between Time Series Masked Reconstruction and Forecasting via Prompt Token Tuning

Lecture notes in computer science (2025)

Hao Liu Jinrui Gan Xiaoxuan Fan Yi Zhang Chuanxian Luo

10.1007/978-981-97-5779-4_10

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A CB2-Selective Cannabinoid Suppresses T-Cell Activities and Increases Tregs and IL-10

Journal of Neuroimmune Pharmacology (2015)

Rebecca Hartzell Robinson Joseph J. Meissler Xiaoxuan Fan Daohai Yu Martin W. Adler

Mixed lymphocyte reaction

NFAT

10.1007/s11481-015-9611-3

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Citations (45)

PT-Tuning: Bridging the Gap between Time Series Masked Reconstruction and Forecasting via Prompt Token Tuning

arXiv (Cornell University) (2023)

Hao Liu Jinrui Gan Xiaoxuan Fan Yi Zhang Chuanxian Luo

Self-supervised learning has been actively studied in time series domain recently, especially for masked reconstruction. Most of these methods follow the "Pre-training + Fine-tuning" paradigm in which a new decoder replaces the pre-trained decoder to fit for a specific downstream task, leading to inconsistency of upstream and downstream tasks. In this paper, we first point out that the unification of task objectives and adaptation for task difficulty are critical for bridging the gap between time series masked reconstruction and forecasting. By reserving the pre-trained mask token during fine-tuning stage, the forecasting task can be taken as a special case of masked reconstruction, where the future values are masked and reconstructed based on history values. It guarantees the consistency of task objectives but there is still a gap in task difficulty. Because masked reconstruction can utilize contextual information while forecasting can only use historical information to reconstruct. To further mitigate the existed gap, we propose a simple yet effective prompt token tuning (PT-Tuning) paradigm, in which all pre-trained parameters are frozen and only a few trainable prompt tokens are added to extended mask tokens in element-wise manner. Extensive experiments on real-world datasets demonstrate the superiority of our proposed paradigm with state-of-the-art performance compared to representation learning and end-to-end supervised forecasting methods.

Fine-tuning

10.48550/arxiv.2311.03768

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