Showing papers by "Jiangang Shen published in 2015"

Fluorescent Probe HKSOX-1 for Imaging and Detection of Endogenous Superoxide in Live Cells and In Vivo.

Abstract: Superoxide anion radical (O2(•-)) is undoubtedly the most important primary reactive oxygen species (ROS) found in cells, whose formation and fate are intertwined with diverse physiological and pathological processes. Here we report a highly sensitive and selective O2(•-) detecting strategy involving O2(•-) cleavage of an aryl trifluoromethanesulfonate group to yield a free phenol. We have synthesized three new O2(•-) fluorescent probes (HKSOX-1, HKSOX-1r for cellular retention, and HKSOX-1m for mitochondria-targeting) which exhibit excellent selectivity and sensitivity toward O2(•-) over a broad range of pH, strong oxidants, and abundant reductants found in cells. In confocal imaging, flow cytometry, and 96-well microplate assay, HKSOX-1r has been robustly applied to detect O2(•-) in multiple cellular models, such as inflammation and mitochondrial stress. Additionally, our probes can be efficiently applied to visualize O2(•-) in intact live zebrafish embryos. These probes open up exciting opportunities for unmasking the roles of O2(•-) in health and disease.

A review: The pharmacology of isoliquiritigenin

Abstract: Isoliquiritigenin (ISL) is one of the bioactive ingredients isolated from the roots of plants belonging to licorice, including Glycyrrhiza uralensis, Mongolian glycyrrhiza, Glycyrrhiza glabra, and so forth. Liquiritigenin is available in common foods and alternative medicine, and its derivative-ISL is applied into food additives and disease treatment like cancer therapy, antibiotic therapy, and so on. This review aims at providing a comprehensive summary of the pharmacological activities of ISL. The information published between 1972 and 2014 from a number of reliable sources including PubMed, ScienceDirect, Springer, and Wiley-Blackwell. The practical application of ISL on the various disease prevention and treatments may stem from its numerous pharmacological properties such as antiinflammatory, anti-microbial, anti-oxidative, anticancer activities, immunoregulatory, hepatoprotective, and cardioprotective effects. However, further studies are needed to verify the target-organ toxicity or side effects investigation.

Dietary compound isoliquiritigenin prevents mammary carcinogenesis by inhibiting breast cancer stem cells through WIF1 demethylation

Abstract: // Neng Wang 1, * , Zhiyu Wang 1, 2, * , Yu Wang 3 , Xiaoming Xie 4 , Jiangang Shen 1 , Cheng Peng 5 , Jieshu You 1 , Fu Peng 1 , Hailin Tang 4 , Xinyuan Guan 6 , Jianping Chen 1, 5 1 School of Chinese Medicine, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Hong Kong 2 Department of Mammary Disease, Guangdong Provincial Hospital of Chinese Medicine, The Second Clinical Medical College, Guangzhou University of Chinese Medicine, Guangdong, China 3 Department of Pharmacology, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Hong Kong 4 Department of Breast Oncology, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center of Cancer Medicine, Guangzhou, China 5 School of Pharmaceutical Science, Chengdu University of Traditional Chinese Medicine, Sichuan, Chengdu, China 6 Department of Clinical Oncology, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Hong Kong * These authors have contributed equally to this work Correspondence to: Jianping Chen, e-mail: jpjpchen@yahoo.com Keywords: mammary tumorigenesis, cancer stem cells, WIF1 demethylation, DNMT1, Isoliquiritigenin Received: December 25, 2014 Accepted: February 15, 2015 Published: March 26, 2015 ABSTRACT Breast cancer stem cells (CSCs) are considered as the root of mammary tumorigenesis. Previous studies have demonstrated that ISL efficiently limited the activities of breast CSCs. However, the cancer prevention activities of ISL and its precise molecular mechanisms remain largely unknown. Here, we report a novel function of ISL as a natural demethylation agent targeting WIF1 to prevent breast cancer. ISL administration suppressed in vivo breast cancer initiation and progression, accompanied by reduced CSC-like populations. A global gene expression profile assay further identified WIF1 as the main response gene of ISL treatment, accompanied by the simultaneous downregulation of β-catenin signaling and G0/G1 phase arrest in breast CSCs. In addition, WIF1 inhibition significantly relieved the CSC-limiting effects of ISL and methylation analysis further revealed that ISL enhanced WIF1 gene expression via promoting the demethylation of its promoter, which was closely correlated with the inhibition of DNMT1 methyltransferase. Molecular docking analysis finally revealed that ISL could stably dock into the catalytic domain of DNMT1. Taken together, our findings not only provide preclinical evidence to demonstrate the use of ISL as a dietary supplement to inhibit mammary carcinogenesis but also shed novel light on WIF1 as an epigenetic target for breast cancer prevention.

Peroxynitrite Decomposition Catalyst Reduces Delayed Thrombolysis-induced Hemorrhagic Transformation in Ischemia-reperfused Rat Brains.

Abstract: Summary Aim Hemorrhagic transformation (HT) is a major complication of delayed tissue plasminogen activator (t-PA) treatment in ischemic stroke. We aimed to explore whether peroxynitrite decomposition catalyst (PDC) could prevent such complication. Methods Male Sprague-Dawley (SD) rats were subjected to middle cerebral artery occlusion (MCAO) with t-PA (10 mg/kg) or t-PA plus FeTMPyP (3 mg/kg, a representative PDC) at MCAO for 2 or 5 h and reperfusion for 22 or 19 h, respectively. HT was assessed with hemoglobin assay. Neurological deficit was evaluated with Modified Neurological Severity Score (mNSS). Peroxynitrite formation was examined by detecting 3-nitrotyrosine (3-NT) formation. The expression and activity of MMP-9/MMP-2 were assessed by Western blotting and gelatin zymography. Results t-PA treatment at 2 h of MCAO did not induce HT but attenuated neurological deficit, whereas treatment at 5 h significantly induced HT and worsened the neurological outcome. Such complications were prevented by FeTMPyP cotreatment. Early t-PA treatment inhibited 3-NT and MMP-9/MMP-2 expression, whereas delayed treatment induced 3-NT and MMP-9/MMP-2 expression and activity. FeTMPyP cotreatment downregulated 3-NT and inhibited MMP-9/MMP-2 in both time points. Conclusion Peroxynitrite decomposition catalyst could prevent hemorrhagic transformation and improve neurological outcome ischemic rat brains with delayed t-PA treatment via inhibiting peroxynitrite-mediated MMP activation.

Whether Metal Element-Containing Herbal Formula Angong Niuhuang Pill Is Safe for Acute Brain Disorders?

Abstract: “Angong Niuhuang Pill” (AGNH Pill) has been used as patented herbal formula for treatment of acute brain disorders including ischemic stroke, hemorrhage stroke, and trauma brain injury in traditional Chinese medicine for a thousand years. It is widely used in treatment of many diseases. As AGNH Pill contains metal elements named realgar and cinnabar, whether AGNH Pill is safe attracts great concerns. To address this question, we reviewed adverse drug reactions (ADR) and adverse events (AE) to assess the safety of AGNH Pill clinically. We searched PubMed, Embase, Cochrane library, TOXNET, and Chinese databases CNKI and Wanfang for articles published between January 1974 and January 2015. A total of 49 cases contained in 10 articles were included in this study. We were unable to determine the frequency of ADR/AE induced by AGNH Pill due to the lack of complete production and market information provided by pharmaceutical manufacturers and hospitals. Based on current literature data, we estimated that the risk of ADR/AE from AGNH Pill administration was low. The majority of ADR/AE was attributed to the improper use of AGNH Pill, such as use in children with overdosage or use with incompatible drugs. We were unable to distinguish whether incidents were ADR or AE because of the poor reports. To date, published evidence indicates that AGNH Pill appears to carry a relatively low risk of ADR/AE. As the quality of clinical assessment for the safety of AGNH Pill is poor, it is desirable to conduct well-designed randomized clinical trials to assess its safety for the treatment of acute brain disorders.

Site-2 protease responds to oxidative stress and regulates oxidative injury in mammalian cells

Abstract: Site-2 protease (S2P) is a membrane-embedded protease that site-specifically cleaves intramembrane transcription factors, a necessary step for their maturation. S2P is well known to regulate cholesterol biosynthesis and endoplasmic reticulum stress in mammalian cells. In this study, we hypothesized that S2P could be responsible for the regulation of cellular oxidative injury under oxidative stress. Wild type Chinese hamster ovary (WT CHO) cells and their mutant M19 cells with defective S2P gene were exposed to different oxidative stress conditions. Results showed that oxidative stress significantly up-regulated S2P expression in WT CHO cells. Notably, M19 cells had remarkably higher level of superoxide and elevated rates of cell death than WT CHO cells. The vulnerability to oxidative stress was reversed by the transfection of S2P gene but not rescued by exogenous supplement of cholesterol, oleate, and mevalonate, indicating that lack of S2P gene leads cells to be more vulnerable to oxidative stress. Furthermore, compared with WT CHO cells, M19 cells had higher nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity and lower paraoxonase-2 expression. Taken together, these results suggest that S2P can be a protease responding to oxidative stress and has the function of regulating cellular oxidative injury.

Wet-season spatial variability in N 2 O emissions from a tea field in subtropical central China

Abstract: . Tea fields emit large amounts of nitrous oxide (N2O) to the atmosphere. Obtaining accurate estimations of N2O emissions from tea-planted soils is challenging due to strong spatial variability. We examined the spatial variability in N2O emissions from a red-soil tea field in Hunan Province, China, on 22 April 2012 (in a wet season) using 147 static mini chambers approximately regular gridded in a 4.0 ha tea field. The N2O fluxes for a 30 min snapshot (10:00–10:30 a.m.) ranged from −1.73 to 1659.11 g N ha−1 d−1 and were positively skewed with an average flux of 102.24 g N ha−1 d−1. The N2O flux data were transformed to a normal distribution by using a logit function. The geostatistical analyses of our data indicated that the logit-transformed N2O fluxes (FLUX30t) exhibited strong spatial autocorrelation, which was characterized by an exponential semivariogram model with an effective range of 25.2 m. As observed in the wet season, the logit-transformed soil ammonium-N (NH4Nt), soil nitrate-N (NO3Nt), soil organic carbon (SOCt) and total soil nitrogen (TSNt) were all found to be significantly correlated with FLUX30t (r = 0.57–0.71, p