Browsing by Author "Xu, Bing"

Now showing 1 - 7 of 7
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    Divergent actions of Myofibroblast and Myocyte β2-Adrenoceptor in Heart Failure and Fibrotic Remodeling
    (American Heart Association, 2023) Deng, Bingqing; Zhang, Yu; Zhu, Chaoqun; Wang, Ying; Weatherford, Eric; Xu, Bing; Liu, Xuanhui; Conway, Simon J.; Abel, E. Dale; Xiang, Yang K.; Pediatrics, School of Medicine
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    Gender Differences in Histamine-Induced Depolarization and Inward Currents in Vagal Ganglion Neurons in Rats
    (Ivyspring, 2013-11-20) Li, Jun-Nan; Qian, Zhao; Xu, Wen-Xiao; Xu, Bing; Lu, Xiao-Long; Yan, Zhen-Yu; Han, Li-Min; Liu, Yang; Yuan, Mei; Schild, John; Qiao, Guo-Fen; Li, Bai-Yan; Biomedical Engineering, Purdue School of Engineering and Technology
    Evidence has shown gender differences regarding the critical roles of histamine in the prevalence of asthma, anaphylaxis, and angina pectoris. Histamine depolarizes unmyelinated C-type neurons without any effects on myelinated A-type vagal ganglion neurons (VGNs) in male rats. However, little is known if VGNs from females react to histamine in a similar manner. Membrane depolarization and inward currents were tested in VGNs isolated from adult rats using a whole-cell patch technique. Results from males were consistent with the literature. Surprisingly, histamine-induced depolarization and inward currents were observed in both unmyelinated C-type and myelinated A- and Ah-type VGNs from female rats. In Ah-type neurons, responses to 1.0 μM histamine were stronger in intact females than in males and significantly reduced in ovariectomized (OVX) females. In C-type neurons, histamine-induced events were significantly smaller (pA/pF) in intact females compared with males and this histamine-induced activity was dramatically increased by OVX. Female A-types responded to histamine, which was further increased following ovariectomy. Histamine at 300 nM depolarized Ah-types in females, but not Ah-types in OVX females. In contrast, the sensitivity of A- and C-types to histamine was upregulated by OVX. These data demonstrate gender differences in VGN chemosensitivity to histamine for the first time. Myelinated Ah-types showed the highest sensitivity to histamine across female populations, which was changed by OVX. These novel findings improve the understanding of gender differences in the prevalence of asthma, anaphylaxis, and pain. Changes in sensitivity to histamine by OVX may explain alterations in the prevalence of certain pathophysiological conditions when women reach a postmenopausal age.
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    Increase in neuroexcitability of unmyelinated C-type vagal ganglion neurons during initial postnatal development of visceral afferent reflex functions
    (Wiley, 2013-12) Qian, Zhao; Liu, Dong‐Jie; Liu, Yang; Han, Li‐Min; Yuan, Mei; Li, Jun‐Nan; Xu, Bing; Lu, Xiao‐Long; Cao, Pan‐Xiang; Wang, Hao‐Yan; Pan, Xiao‐Dong; Wang, Li‐Juan; Qiao, Guo‐Fen; Li, Bai‐Yan; Biology, School of Science
    BACKGROUND: Baroreflex gain increase up closely to adult level during initial postnatal weeks, and any interruption within this period will increase the risk of cardiovascular problems in later of life span. We hypothesize that this short period after birth might be critical for postnatal development of vagal ganglion neurons (VGNs). METHODS: To evaluate neuroexcitability evidenced by discharge profiles and coordinate changes, ion currents were collected from identified A- and C-type VGNs at different developmental stages using whole-cell patch clamping. RESULTS: C-type VGNs underwent significant age-dependent transition from single action potential (AP) to repetitive discharge. The coordinate changes between TTX-S and TTX-R Na(+) currents were also confirmed and well simulated by computer modeling. Although 4-AP or iberiotoxin age dependently increased firing frequency, AP duration was prolonged in an opposite fashion, which paralleled well with postnatal changes in 4-AP- and iberiotoxin-sensitive K(+) current activity, whereas less developmental changes were verified in A-types. CONCLUSION: These data demonstrate for the first time that the neuroexcitability of C-type VGNs increases significantly compared with A-types within initial postnatal weeks evidenced by AP discharge profiles and coordinate ion channel changes, which explain, at least in part, that initial postnatal weeks may be crucial for ontogenesis in visceral afferent reflex function.
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    Lipopolysaccharide treatment induces genome-wide pre-mRNA splicing pattern changes in mouse bone marrow stromal stem cells
    (BioMed Central, 2016-08-22) Zhou, Ao; Li, Meng; He, Bo; Feng, Weixing; Huang, Fei; Xu, Bing; Dunker, A. Keith; Balch, Curt; Li, Baiyan; Liu, Yunlong; Wang, Yue; Department of Medical and Molecular Genetics, IU School of Medicine
    Background Lipopolysaccharide (LPS) is a gram-negative bacterial antigen that triggers a series of cellular responses. LPS pre-conditioning was previously shown to improve the therapeutic efficacy of bone marrow stromal cells/bone-marrow derived mesenchymal stem cells (BMSCs) for repairing ischemic, injured tissue. Results In this study, we systematically evaluated the effects of LPS treatment on genome-wide splicing pattern changes in mouse BMSCs by comparing transcriptome sequencing data from control vs. LPS-treated samples, revealing 197 exons whose BMSC splicing patterns were altered by LPS. Functional analysis of these alternatively spliced genes demonstrated significant enrichment of phosphoproteins, zinc finger proteins, and proteins undergoing acetylation. Additional bioinformatics analysis strongly suggest that LPS-induced alternatively spliced exons could have major effects on protein functions by disrupting key protein functional domains, protein-protein interactions, and post-translational modifications. Conclusion Although it is still to be determined whether such proteome modifications improve BMSC therapeutic efficacy, our comprehensive splicing characterizations provide greater understanding of the intracellular mechanisms that underlie the therapeutic potential of BMSCs. Electronic supplementary material The online version of this article (doi:10.1186/s12864-016-2898-5) contains supplementary material, which is available to authorized users.
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    Lipopolysaccharides Improve Mesenchymal Stem Cell-Mediated Cardioprotection by MyD88 and stat
    (Mary Ann Liebert, 2019-04-25) Chu, Xiaona; Xu, Bing; Gao, Hongyu; Li, Bai-Yan; Liu, Yunlong; Reiter, Jill L.; Wang, Yue; Medical and Molecular Genetics, School of Medicine
    Bone marrow-derived mesenchymal stem cells (MSCs) improve cardiac function after ischemia/reperfusion injury, in part, due to the release of cytoprotective paracrine factors. Toll-like receptor 4 (TLR4) is expressed in MSCs and regulates the expression of cytoprotective factors, cytokines, and chemokines. Lipopolysaccharide (LPS) stimulation of TLR4 activates two distinct signaling pathways that are either MyD88 dependent or MyD88 independent/TIR-domain-containing adapter-inducing interferon-β (TRIF) dependent. While it was reported previously that LPS treatment improved MSC-mediated cardioprotection, the mechanism underlying such improved effect remains unknown. To study the role of MyD88 signaling in MSC cardioprotective activity, wild type (WT) and MyD88-/- MSCs were treated with LPS (200 ng/mL) for 24 h. WT and MyD88-/- MSCs with or without LPS pretreatment were infused into the coronary circulation of isolated mouse hearts (Langendorff model) and then subjected to ischemia (25 min) and reperfusion (50 min). Saline served as a negative control. Both untreated and LPS-pretreated WT MSCs significantly improved postischemic recovery of myocardial function of isolated mouse hearts, as evidenced by improved left ventricular developed pressure and ventricular contractility assessment (ie, the rate of left ventricle pressure change over time, ± dp/dt). LPS-pretreated WT MSCs conferred better cardiac function recovery than untreated MSCs; however, such effect of LPS was abolished when using MyD88-/- MSCs. In addition, LPS stimulated stat3 activity in WT MSCs, but not MyD88-/- MSCs. stat3 small interfering RNA abolished the effect of LPS in improving the cardioprotection of WT MSCs. In conclusion, this study demonstrates that LPS improves MSC-mediated cardioprotection by MyD88-dependent activation of stat3.
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    Optogenetic Control of Engrafted Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes in Live Mice: A Proof-of-Concept Study
    (MDPI, 2022-03-10) Joshi, Jyotsna; Xu, Bing; Rubart, Michael; Chang, Yun; Bao, Xiaoping; Chaliki, Hari P.; Scott, Luis R.; Zhu, Wuqiang; Pediatrics, School of Medicine
    Background: Cellular transplantation has emerged as promising approach for treating cardiac diseases. However, a poor engraftment rate limits our understanding on how transplanted cardiomyocytes contribute to cardiac function in the recipient’s heart. Methods: The CRISPR/Cas9 technique was employed for stable and constitutive gene expression in human-induced pluripotent stem-cell-derived cardiomyocytes (hiPSC-CMs). Myocardial infarction was induced in adult immunodeficient mice, followed by intramyocardial injection of hiPSC-CMs expressing either CCND2/channelrhodopsin 2 (hiPSC-CCND2OE/ChR2OECMs) or CCND2/luciferase (hiPSC-CCND2OE/LuciOECMs). Six months later, hemodynamics and intramural electrocardiogram were recorded upon blue light illuminations in anesthetized, open-chest mice. Results: Blue light resets automaticity of spontaneously beating hiPSC-CCND2OE/ChR2OECMs in culture, but not that of hiPSC-CCND2OE/LuciOECMs. Response to blue light was also observed in mice carrying large (>106 cells) intracardiac grafts of hiPSC-CCND2OE/ChR2OECM but not in mice carrying hiPSC-CCND2OE/LuciOECMs. The former exhibited single premature ventricular contractions upon light illumination or ventricular quadrigeminy upon second-long illuminations. At the onset of premature ventricular contractions, maximal systolic ventricular pressure decreased while ventricular volume rose concomitantly. Light-induced changes reversed upon resumption of sinus rhythm. Conclusions: We established an in vivo model for optogenetic-based modulation of the excitability of donor cardiomyocytes in a functional, reversible, and localized manner. This approach holds unique value for studying electromechanical coupling and molecular interactions between donor cardiomyocytes and recipient hearts in live animals.
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    Subtype Identification in Acutely Dissociated Rat Nodose Ganglion Neurons Based on Morphologic Parameters
    (Ivyspring, 2013-07-27) Lu, Xiao-Long; Xu, Wen-Xiao; Yan, Zhen-Yu; Qian, Zhao; Xu, Bing; Liu, Yang; Han, Li-Min; Gao, Rui-Chen; Li, Jun-Nan; Yuan, Mei; Zhao, Chong-Bao; Qiao, Guo-fen; Li, Bai-Yan; Pediatrics, School of Medicine
    Nodose ganglia are composed of A-, Ah- and C-type neurons. Despite their important roles in regulating visceral afferent function, including cardiovascular, pulmonary, and gastrointestinal homeostasis, information about subtype-specific expression, molecular identity, and function of individual ion transporting proteins is scarce. Although experiments utilizing the sliced ganglion preparation have provided valuable insights into the electrophysiological properties of nodose ganglion neuron subtypes, detailed characterization of their electrical phenotypes will require measurements in isolated cells. One major unresolved problem, however, is the difficulty to unambiguously identify the subtype of isolated nodose ganglion neurons without current-clamp recording, because the magnitude of conduction velocity in the corresponding afferent fiber, a reliable marker to discriminate subtypes in situ, can no longer be determined. Here, we present data supporting the notion that application of an algorithm regarding to microscopic structural characteristics, such as neuron shape evaluated by the ratio between shortest and longest axis, neuron surface characteristics, like membrane roughness, and axon attachment, enables specific and sensitive subtype identification of acutely dissociated rat nodose ganglion neurons, by which the accuracy of identification is further validated by electrophysiological markers and overall positive predictive rates is 89.26% (90.04%, 76.47%, and 98.21% for A-, Ah, and C-type, respectively). This approach should aid in gaining insight into the molecular correlates underlying phenotypic heterogeneity of nodose ganglia. Additionally, several critical points that help for neuron identification and afferent conduction calibration are also discussed.