Showing papers by "Jiangang Shen published in 2016"
TL;DR: An ultra-selective and ultra-sensitive HOCI fluorescent probe HKOCl-3 for live-cell and in vivo imaging and quantitative applications is described.
Abstract: Ultra-selective and ultra-sensitive probes for hypochlorous acid (HOCl), one of the most poorly understood reactive oxygen species (ROS), are urgently needed to unravel the HOCl functions in important biological processes such as development and innate immunity. Based on a selective oxidative O-dearylation reaction of 2,6-dichlorophenol toward HOCl over other reactive oxygen species, we have developed a novel fluorescent probe HKOCl-3 for HOCl detection with ultra-selectivity, ultra-sensitivity and a rapid turn-on response. The functional robustness of HKOCl-3 for endogenous HOCl detection and imaging has been thoroughly scrutinized in multiple types of phagocytes and in vivo imaging of live intact zebrafish embryos. Furthermore, HKOCl-3 has been successfully applied to the detection of endogenous HOCl by a 96-well microplate assay and flow cytometry. Therefore, HKOCl-3 holds great promise as a versatile molecular tool that enables innovative investigation of HOCl biology and ROS-related diseases in multiple detection modalities.
129 citations
TL;DR: A novel fluorescent reporter HKYellow was rationally designed for the robust visualization of peroxynitrite production in live cells and tissues.
Abstract: Herein, we present the rational design, synthesis, characterization, and biological applications of a new rhodamine-based fluorescent probe, HKYellow, for the detection and molecular imaging of peroxynitrite, an important highly reactive oxidant involved in a variety of physiological and pathological processes. HKYellow was rationally designed on the basis of the efficient fluorescence quenching effect of the N-phenyl group to the rhodamine core and a peroxynitrite-triggered N-dearylation reaction to achieve a sensitive and selective fluorescence turn-on response toward peroxynitrite in chemical and biological levels. This probe has been thoroughly evaluated for the robust imaging of peroxynitrite in live cells and tissues. By utilizing HKYellow, we provide the first visual evidence that peroxynitrite is generated in mouse liver tissues under an acute alcohol binge or ischemic–reperfusion condition. This probe should be a powerful molecular imaging tool for interrogating the complex biological roles of peroxynitrite under various biological settings.
111 citations
TL;DR: Current progress about molecular targets involving in t-PA-mediated HT and neurotoxicity in ischemic brain injury are summarized and 23 promising compounds from currently available literature with the bioactivities simultaneously targeting several important molecular targets are selected.
Abstract: Tissue plasminogen activator (t-PA) is the only FDA-approved drug for acute ischemic stroke treatment, but its clinical use is limited due to the narrow therapeutic time window and severe adverse effects, including hemorrhagic transformation (HT) and neurotoxicity. One of the potential resolutions is to use adjunct therapies to reduce the side effects and extend t-PAa#039;s therapeutic time window. However, therapies modulating single target seem not to be satisfied, and a multitarget strategy is warranted to resolve such complex disease. Recently, large amount of efforts have been made to explore the active compounds from herbal supplements to treat ischemic stroke. Some natural compounds revealed both neuro- and bloodbrain- barrier (BBB)-protective effects by concurrently targeting multiple cellular signaling pathways in cerebral ischemia-reperfusion injury. Thus, those compounds are potential to be one-drug-multi-target agents as combined therapy with t-PA for ischemic stroke. In this review article, we summarize current progress about molecular targets involving in t-PA-mediated HT and neurotoxicity in ischemic brain injury. Based on these targets, we select 23 promising compounds from currently available literature with the bioactivities simultaneously targeting several important molecular targets. We propose that those compounds merit further investigation as combined therapy with t-PA. Finally, we discuss the potential drawbacks of the natural compoundsa#039; studies and raise several important issues to be addressed in the future for the development of natural compound as an adjunct therapy.
70 citations
TL;DR: A novel mechanism of cerebral ischemia-induced blood-brain barrier damage is revealed, and zinc is implicate as an effective and viable new target for reducing acute BBB damage following ischemic stroke.
42 citations
TL;DR: In vitro knockdown of caveolin-1 compromised the upregulation of ICAM-1 in endothelial cells, leading to the amelioration of the transendothelial migration of pathogenic TH1 and TH17 cells, highlighting the pathological involvement of caveolina in neuroinflammatory diseases.
Abstract: Multiple sclerosis (MS) is a progressive autoimmune disease of the CNS with its underlying mechanisms not fully understood. In the present study, we tested the hypothesis that caveolin-1, a major membrane scaffolding protein, plays a critical role in the pathogenesis of experimental autoimmune encephalomyelitis, a laboratory murine model of MS. We found increased expression of caveolin-1 in serum and spinal cord tissues in association with disease incidence and severity in wild-type mice with active encephalomyelitis. After immunization, Cav-1 knock-out mice showed remarkable disease resistance with decreased incidence and clinical symptoms. Furthermore, Cav-1 knock-out mice had alleviated encephalitogenic T cells trafficking into the CNS with decreased expressions of adhesion molecules ICAM-1 and VCAM-1 within the lesions. In agreement with in vivo studies, in vitro knockdown of caveolin-1 compromised the upregulation of ICAM-1 in endothelial cells, leading to the amelioration of the transendothelial migration of pathogenic T H 1 and T H 17 cells. Together, those results indicate that caveolin-1 serves as an active modulator of CNS-directed lymphocyte trafficking and could be a therapeutic target for neuroinflammatory diseases, such as multiple sclerosis. SIGNIFICANCE STATEMENT The hallmark feature of neuroinflammatory diseases is the massive infiltrations of encephalitogenic leukocytes into the CNS parenchyma, a process that remains largely unclear. Our study demonstrates the critical contribution of caveolin-1 to encephalomyelitis pathogenesis and CNS-directed lymphocyte trafficking by modulation of adhesion molecules ICAM-1 and VCAM-1, highlighting the pathological involvement of caveolin-1 in neuroinflammatory diseases.
28 citations
TL;DR: It is concluded that Cav-1 could play a critical role in preventing nitrative stress-induced liver damage during hepatic ischemia-reperfusion injury.
27 citations
08 Dec 2016
TL;DR: The roles and interactions of these three targets in mediating HT are analyzed; the potential compounds from Chinese herbal medicine for attenuating HT are summarized and analyzed and the potential issues are raised.
Abstract: Stroke is the leading cause of death and disability worldwide, and ischemic stroke accounts for more than 85% of the stroke incidence. Tissue plasminogen activator (t-PA) is the only FDA-approved drug for ischemic stroke treatment with a narrow treatment time window of 4.5 h. Hemorrhagic transformation (HT) is a severe complication of delayed t-PA treatment in ischemic stroke. Thus, it is critically important to develop combination therapies to reduce HT and extend the therapeutic time window of t-PA. Current progress suggests that peroxynitrite (ONOO-)/high-mobility group box 1 protein (HMGB1)/matrix metalloproteinase-9 (MMP-9) signaling cascades could be important for attenuating HT during thrombolytic treatment for acute ischemic stroke. Recently, important progress has been made in seeking for natural compounds from Chinese medicine for reducing ischemic stroke injury, with some of them targeting ONOO-/HMGB1/MMP-9 signaling cascades. Herein, we analyze the roles and interactions of these three targets in mediating HT; subsequently, we summarize the potential compounds from Chinese herbal medicine for attenuating HT and analyze the related targets. Finally, we raise the potential issues to be addressed in further development of these compounds as combination therapy.
13 citations
TL;DR: The radial X-ray camera (RXC) as mentioned in this paper was designed to measure the poloidal profile of plasma Xray emission with high spatial and temporal resolution, and its primary diagnostic role includes measuring low (m,...
Abstract: The radial X-ray camera (RXC) is designed to measure the poloidal profile of plasma X-ray emission with high spatial and temporal resolution. Its primary diagnostic role includes measuring low (m, ...
13 citations
TL;DR: In vitro knockdown of caveolin-1 impaired the up-regulation of ICAM-1 in endothelial cells, and ameliorated trans-endothelial migration of pathogenic TH1 and TH17 cells, which serves as an active modulator of lymphocyte trafficking into CNS and could be a therapeutic target for multiple sclerosis.
4 citations
3 citations
TL;DR: Glycyrrhizin could be an adjuvant therapy with t-PA to improve the therapeutic outcome for ischemic stroke by inhibiting HMGB1 and MMP-9 and reducing HT.
TL;DR: It should be noted that, in Figure 5, the authors display only the target tissues (i.e., smooth muscles of the aortic root) that are of relevance and interest to the atherosclerosis model for comparison of peroxynitrite levels.
Abstract: Page 11728. Derek Hoi-Hang Ho, at his request and with the agreement of all co-authors, is removed as an author of this article. Page 11733. It should be noted that, in Figure 5, we display only the target tissues (i.e., smooth muscles of the aortic root) that are of relevance and interest to the atherosclerosis model for comparison of peroxynitrite levels. Although the surrounding tissues (i.e., cardiac muscles) have greater fluorescence than the tissues of interest (i.e., smooth muscles), they may not be relevant to the atherosclerosis model reported. The original uncropped images of Figure 5 are included as Figure S20 in the revised Supporting Information. Supporting Information. Similarly, in Figure S16, only the target tissues (i.e., smooth muscles) are displayed and compared, whereas surrounding tissues are cropped out for simple illustration. The original uncropped images of Figure S16 are included as Figure S21 in the revised Supporting Information.