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Xie Z.-Z.,University of South China | Xie Z.-Z.,Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study | Liu Y.,University of South China | Liu Y.,Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study | Bian J.-S.,National University of Singapore
Oxidative Medicine and Cellular Longevity | Year: 2016

Intracellular redox imbalance is mainly caused by overproduction of reactive oxygen species (ROS) or weakness of the natural antioxidant defense system. It is involved in the pathophysiology of a wide array of human diseases. Hydrogen sulfide (H2S) is now recognized as the third "gasotransmitters" and proved to exert a wide range of physiological and cytoprotective functions in the biological systems. Among these functions, the role of H2S in oxidative stress has been one of the main focuses over years. However, the underlying mechanisms for the antioxidant effect of H2S are still poorly comprehended. This review presents an overview of the current understanding of H2S specially focusing on the new understanding and mechanisms of the antioxidant effects of H2S based on recent reports. Both inhibition of ROS generation and stimulation of antioxidants are discussed. H2S-induced S-sulfhydration of key proteins (e.g., p66Shc and Keap1) is also one of the focuses of this review. © 2016 Zhi-Zhong Xie et al.


Yu W.,Wuhan University | Yang Y.,CAS Wuhan Institute of Physics and Mathematics | Bo S.,Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study | Bo S.,University of South China | And 8 more authors.
Journal of Organic Chemistry | Year: 2015

To achieve high sensitivity for 19F MRI, a class of novel dendritic molecules with multiple pseudosymmetrical fluorines was designed and efficiently synthesized. Through iterative bromination and Williamson ether synthesis under mild conditions, a fluorinated dendrimer with 540 pseudosymmetrical fluorines was conveniently prepared without performing the group protection in a convergent way. The dendrimer is characterized by a strong 19F NMR peak and short relaxation times. Eventually, an appreciably enhanced 19F MRI at an extremely low concentration (18.5 μM) was achieved, which demonstrated the potential utility of such dendritic molecules in highly sensitive 19F MRI. (Chemical Equation Presented). © 2015 American Chemical Society.


Zhou J.,University of South China | Zhou J.,Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study | Zhang J.,Fudan University | Ren H.,Fudan University | And 4 more authors.
Chinese Journal of Chemistry | Year: 2016

A novel turn-on fluorescent probe for the detection of palladium has been designed. The probe can selectively and sensitively detect palladium in solution, and the limit of detection was calculated to be 11.4 nmol·L-1. Furthermore, the probe was successfully used for fluorescence imaging of palladium in living cells. © 2016 SIOC, CAS, Shanghai & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Ma Y.,University of South China | Ma Y.,Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study | Tian S.,University of South China | He S.,University of South China | And 6 more authors.
Gene | Year: 2016

The biological effects of microRNAs (miRNAs) in the Fragile X Syndrome (FXS) have been widely studied. Dysregulation of miRNAs plays a critical role in the progression of nervous system diseases and in cell proliferation and differentiation. Our previous study validated that miR-19b-3p was associated with FXR1 (Fragile X related gene 1), one of homologous genes of FMR1 (Fragile X mental retardation 1). The purpose of this study was to investigate the relationship of FXR1 and miR-19b-3p, and the crucial role of miR-19b-3p in FXS and to validate whether miR-19b-3p could regulate the growth of SH-SY5Y cells. We determined that miR-19b-3p could regulate the expression of not only USP32, RAB18 and Dusp6 but also FXR1, and FXR1 could in turn regulate the expression of miR-19b-3p. What's more, the overexpression of miR-19b-3p significantly inhibited the proliferation, contributed the apoptosis and slowed down the cycle of SH-SY5Y cells. Taken together, our results indicate that miR-19b-3p plays a significant role in the molecular pathology of FXS by interacting with FXR1 and influencing the growth of SH-SY5Y cells. © 2016 Elsevier B.V.


Xiao F.,University of South China | Zhang P.,University of South China | Chen A.-H.,University of South China | Wang C.-Y.,University of South China | And 4 more authors.
Experimental Cell Research | Year: 2016

We have previously demonstrated the protective action of hydrogen sulfide (H2S) in 1-Methy-4-Phenylpyridinium Ion (MPP+)-induced neurotoxicity. However, the exact mechanisms of this protection remain largely unknown. Aldehyde stress and endoplasmic reticulum (ER) stress play significant roles in the neurotoxicity of MPP+. Brain derived neurotrophic factor (BDNF) is an important endogenous neuroprotectant. Therefore, we speculated that the protection of H2S against MPP+ neurotoxicity results from inhibiting MPP+-induced aldehyde stress and ER stress via upregulation of BDNF. In the present study, we found that NaHS, a donor of H2S, inhibited MPP+-induced aldehyde stress (the accumulations of the intracellular 4-HNE and MDA) and ER stress (the increases in the expressions of GRP78 and Cleaved-caspase-12) in PC12 cells and upregulated the BDNF expression in MPP+-exposed PC12 cells. Furthermore, we found that pretreatment of PC12 cells with K252a, an inhibitor of the BDNF receptor TrkB, not only markedly reversed the inhibitiory role of NaHS in MPP+-induced aldehyde stress and ER stress, but also ablated the protection of NaHS against MPP+-induced neurotoxicity. These data demonstrated that the protective role of H2S against MPP+-induced neurotoxicity by inhibiting aldehyde stress and ER stress, which is involved in upregulation of BDNF. © 2016 Elsevier Inc.


PubMed | Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study and University of South China
Type: | Journal: BioMed research international | Year: 2015

Perfluorooctane sulfonate (PFOS), a ubiquitous environmental pollutant, is neurotoxic to mammalian species. However, the underlying mechanism of its neurotoxicity was unclear. We hypothesized that PFOS suppresses BDNF expression to produce its neurotoxic effects by inhibiting the ERK-CREB pathway. SH-SY5Y human neuroblastoma cells were exposed to various concentrations of PFOS to examine the role of the BDNF-ERK-CREB signalling pathway in PFOS-induced apoptosis and cytotoxicity. Furthermore, to ascertain the mechanism by which PFOS reduces BDNF signalling, we examined the expression levels of miR-16 and miR-22, which potentially regulate BDNF mRNA translation at the posttranscriptional level. Results indicated that PFOS significantly decreased cell viability and induced apoptosis in SH-SY5Y cells. In addition, BDNF and pERK protein levels decreased after PFOS treatment; however, pCREB protein levels were significantly elevated in PFOS treated groups. TrkB protein expression increased in the 10M and 50M PFOS groups and significantly decreased in the 100M PFOS group. Our results demonstrated that PFOS exposure decreased miR-16 expression and increased miR-22 expression, which may represent a possible mechanism by which PFOS decreases BDNF protein levels. PFOS may inhibit BDNF-ERK-CREB signalling by increasing miR-22 levels, which may, in part, explain the mechanism of PFOS neurotoxicity.


PubMed | Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Central South University and University of South China
Type: Journal Article | Journal: Gene | Year: 2016

The biological effects of microRNAs (miRNAs) in the Fragile X Syndrome (FXS) have been widely studied. Dysregulation of miRNAs plays a critical role in the progression of nervous system diseases and in cell proliferation and differentiation. Our previous study validated that miR-19b-3p was associated with FXR1 (Fragile X related gene 1), one of homologous genes of FMR1 (Fragile X mental retardation 1). The purpose of this study was to investigate the relationship of FXR1 and miR-19b-3p, and the crucial role of miR-19b-3p in FXS and to validate whether miR-19b-3p could regulate the growth of SH-SY5Y cells. We determined that miR-19b-3p could regulate the expression of not only USP32, RAB18 and Dusp6 but also FXR1, and FXR1 could in turn regulate the expression of miR-19b-3p. Whats more, the overexpression of miR-19b-3p significantly inhibited the proliferation, contributed the apoptosis and slowed down the cycle of SH-SY5Y cells. Taken together, our results indicate that miR-19b-3p plays a significant role in the molecular pathology of FXS by interacting with FXR1 and influencing the growth of SH-SY5Y cells.


Wan Z.,Wuhan University of Technology | Li Y.,Wuhan University of Technology | Bo S.,Wuhan University of Technology | Gao M.,Wuhan University of Technology | And 8 more authors.
Organic and Biomolecular Chemistry | Year: 2016

Although monodisperse polyethylene glycols (M-PEGs) above 4000 Da are especially valuable in biomedical applications, their synthesis remains a long-standing challenge. To this end, a peptide-based strategy for such M-PEGs was developed. With macrocyclic sulfates as the key intermediates, a panel of oligoethylene glycol (OEG) containing ω-amino acids were prepared with high efficiency. Through solid phase peptide synthesis (SPPS), these amino acids were conveniently assembled into a series of amide bond-containing M-PEGs with high flexibility in molecular weight and amide density selection. With this strategy, an M-PEG of 10262 Da was prepared on a gram scale and its biocompatibility was assessed in a mice model. © The Royal Society of Chemistry 2016.


Xia G.,Wuhan University | Li Y.,Wuhan University | Yang Z.,Wuhan University | Yang Z.,Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study | And 3 more authors.
Organic Process Research and Development | Year: 2015

We have developed a process for the efficient and scalable preparation of heterofunctionalized dodecaethylene glycol from the readily available tetraethylene glycol and its macrocyclic sulfate. By employing the benzyl group as both a protecting group and a separative tag, multiple chromatographic separations were avoided. With this method, α-amino-ω-methyl-dodecaethylene glycol was prepared on a 53 g scale with high purity and 61% overall yield in eight steps and one chromatographic separation. © 2015 American Chemical Society.


PubMed | Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, CAS Wuhan Institute of Physics and Mathematics and Wuhan University
Type: Journal Article | Journal: The Journal of organic chemistry | Year: 2015

To achieve high sensitivity for (19)F MRI, a class of novel dendritic molecules with multiple pseudosymmetrical fluorines was designed and efficiently synthesized. Through iterative bromination and Williamson ether synthesis under mild conditions, a fluorinated dendrimer with 540 pseudosymmetrical fluorines was conveniently prepared without performing the group protection in a convergent way. The dendrimer is characterized by a strong (19)F NMR peak and short relaxation times. Eventually, an appreciably enhanced (19)F MRI at an extremely low concentration (18.5 M) was achieved, which demonstrated the potential utility of such dendritic molecules in highly sensitive (19)F MRI.

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