Publications by authors named "Xiaohong An"

14 Publications

  • Page 1 of 1

Protoporphyrin IX Stimulates Melanogenesis, Melanocyte Dendricity, and Melanosome Transport Through the cGMP/PKG Pathway.

Front Pharmacol 2020 11;11:569368. Epub 2020 Sep 11.

Department of Pharmacy, The First People's Hospital of Changzhou, The Third Affiliated Hospital of Soochow University, Changzhou, China.

Protoporphyrin IX (PPIX) is a heterocyclic organic compound that is the last intermediate in the heme biosynthetic pathway. PPIX, due to its photodynamic effects, is utilized in the treatment of skin diseases. Furthermore, PPIX has been utilized as a melanogenesis-stimulating agent in various studies. However, the exact function and mechanism underlying PPIX action in melanocytes remain to be elucidated. In the present study, we sought to further investigate how PPIX affects melanocyte melanogenesis, and whether PPIX is involved in melanin transport. Our findings demonstrated that PPIX increased melanocyte dendricity and melanosome transport, in addition to increasing melanogenesis. PPIX functions primarily by activating the guanylate cyclase (GC) and cyclic guanosine 3', 5'-monophosphate/protein kinase G (cGMP/PKG) signaling pathways. Once activated, these pathways increase tyrosinase activity and the expression of microphthalmia-associated transcription factor (MITF), tyrosinase, tyrosinase-related protein-1 and -2 (TRP-1 and TRP-2), myosin Va, melanophinin, Ras-related protein Rab-27A (Rab27a), and cell division cycle 42 (Cdc42), promoting melanogenesis, melanocyte dendricity, and melanosome transport. Furthermore, the melanogenic effects of PPIX were confirmed in a zebrafish model system. Our results indicate that PPIX is not cytotoxic and may, thus, be utilized as a pigmentation enhancer.
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http://dx.doi.org/10.3389/fphar.2020.569368DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7516199PMC
September 2020

A Small β-Carboline Derivative "B-9-3" Modulates TGF-β Signaling Pathway Causing Tumor Regression .

Front Pharmacol 2018 19;9:788. Epub 2018 Jul 19.

State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of TCM Evaluation and Translational Research, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, China.

Targeting tumor microenvironment (TME) is crucial in order to overcome the anti-cancer therapy resistance. In this study, we report the antitumor activity of a newly synthesized β-carboline derivative "B-9-3." Here, this small molecule showed a promising antitumor activity along with an enhanced immune response as reflected by a reduction of regulatory T cells and increased CD4+/CD8+ T cells. Further, B-9-3 decreased the number of myofibroblasts not only in the tumor but also in the lung suggesting an anti-metastatic action. The reduction of myofibroblasts was associated with lower expression of epithelial-to-mesenchymal transition markers and a decrease of phosphorylated SMAD2/3 complex indicating the implication of TGF-β signaling pathway in B-9-3's effect. The blockade of myofibroblasts induction by B-9-3 was also verified in human fibroblasts treated with TGF-β. To elucidate the mechanism of B-9-3's action on TGF-β pathway, first, we investigated the molecular interaction between B-9-3 and TGF-β receptors using docking method. Data showed a weak interaction of B-9-3 with the ATP-binding pocket of TGFβRI but a strong one with a ternary complex formed of extracellular domains of TGFβRI, TGFβRII, and TGF-β. In addition, the role of TGFβRI and TGFβRII in B-9-3's activity was explored . B-9-3 did not decrease any of the two receptors' protein level and only reduced phosphorylated SMAD2/3 suggesting that its effect was more probably due to its interaction with the ternary complex rather than decreasing the expression of TGF-β receptors or interfering with their ATP-binding domains. B-9-3 is a small active molecule which acts on the TGF-β signaling pathway and improves the TME to inhibit the proliferation and the metastasis of the tumor with the potential for clinical application.
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http://dx.doi.org/10.3389/fphar.2018.00788DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6063040PMC
July 2018

IL-17 induces cellular stress microenvironment of melanocytes to promote autophagic cell apoptosis in vitiligo.

FASEB J 2018 09 3;32(9):4899-4916. Epub 2018 Apr 3.

State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China.

Vitiligo is a depigmentary disorder that develops as a result of the progressive disappearance of epidermal melanocytes. Stress can precipitate or exacerbate a skin disease through psychosomatic mechanisms. Stress exposure induces vitiligo-like symptoms in mice, as cellular damage to melanocytes causes synthetic pigment loss. Stress also increases IL-17, IL-1β, and antimelanocyte IgG in model mouse serum. Up-regulation of the IL-1β transcript in patients suggests its possible role in autoimmune pathogenesis of vitiligo. We demonstrate that IL-17 promoted IL-1β secretion from keratinocytes. Mitochondrial dysfunction, which can induce the excessive production of reactive oxygen species (ROS), is emerging as a mechanism that underlies various inflammatory and autoimmune diseases. In this study, we demonstrate that IL-17 inhibits melanogenesis of zebrafish, normal human epidermal melanocytes, and B16F10 cells. IL-17 increased mitochondrial dysfunction and ROS accumulation, which was related to autophagy induction. Autophagy is needed for autophagic apoptosis of B16F10 cells induced by IL-17. To inhibit ROS generation, B16F10 cells were pretreated with N-acetyl-l-cysteine (NAC), which inhibited autophagy. 3-Methyladenine (3-MA) also had an inhibiting effect on autophagy. NAC or 3-MA pretreatments inhibited IL-17-mediated cell apoptosis. In summary, IL-17 induces the cellular stress microenvironment in melanocytes to promote autophagic cell apoptosis in vitiligo.-Zhou, J., An, X., Dong, J., Wang, Y., Zhong, H., Duan, L., Ling, J., Ping, F., Shang, J. IL-17 induces cellular stress microenvironment of melanocytes to promote autophagic cell apoptosis in vitiligo.
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http://dx.doi.org/10.1096/fj.201701242RRDOI Listing
September 2018

A novel peptide shows excellent anti-HIV-1 potency as a gp41 fusion inhibitor.

Bioorg Med Chem Lett 2018 03 31;28(5):910-914. Epub 2018 Jan 31.

College of Life Science and Bioengineering, Beijing University of Technology, Beijing 100124, China; State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Viral Disease Control and Prevention, Chinese Centre for Disease Control and Prevention, Beijing 100052, China. Electronic address:

Fusion inhibitors of HIV prevent the virus from entering into the target cell via the interaction with gp41, which stops the process of spatial rearrangement of the viral envelope protein. A series of peptides have been designed and screened to obtain a highly potent novel sequence. Among them, CT105 possesses the most potent anti-viral ability at low nanomolar IC50 values against a panel of HIV-1 pseudoviruses from A, B, C and A/D subtypes, whereas T20 shows much weaker potency. CT105 also shows excellent inhibitory activity at 260 pico molar IC50 against HIV-1 replication. As a fusion inhibitor, CT105 has a strong ability to interrupt gp41 core formation. The terminal half-life of CT105 possesses 1.72-fold longer than that of T20 as determined by developing an indirect competitive ELISA method. The results suggest that this artificial peptide CT105 could be a favorable architype for further optimization and modification.
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http://dx.doi.org/10.1016/j.bmcl.2018.01.061DOI Listing
March 2018

NK1R/5-HT1AR interaction is related to the regulation of melanogenesis.

FASEB J 2018 06 7;32(6):3193-3214. Epub 2018 Feb 7.

State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China.

Substance P (SP) is a candidate mediator along the brain-skin axis and can mimic the effects of stress to regulate melanogenesis. Previously, we and others have found that the regulation of SP for pigmentary function was mediated by neurokinin 1 receptor (NK1R). Emerging evidence has accumulated that psychologic stress can induce dysfunction in the cutaneous serotonin 5-hydroxytryptamine (5-HT)-5-HT1A/1B receptor system, thereby resulting in skin hypopigmentation. Moreover, NK1R and 5-HTR (except 5-HT3) belong to GPCR. The present study aimed at assessing the possible existence of NK1R-5-HTR interactions and related melanogenic functions. Western blot and PCR detection revealed that SP reduced expression of 5-HT1A receptor via the NK1 receptor. Biochemical analyses showed that NK1R and 5-HT1AR could colocalize and interact in a cell and in the skin. When the N terminus of the NK1R protein was removed NK1R surface targeting was prevented, the interaction between NK1R-5-HT1AR decreased, and the depigmentation caused by SP and WAY100635 could be rescued. Importantly, pharmaceutical coadministration of NK1R agonist (SP) and 5-HT1A antagonist (WAY100635) enhanced the NK1-5-HT1A receptor coimmunoprecipitation along with the depigmentary response. SP and WAY100635 cooperation elicited activation of a signaling cascade (the extracellular, regulated protein kinase p-JNK signaling pathway) and inhibition of p70S6K1 phosphorylation and greatly reduced melanin production in vitro and in vivo in mice and zebrafish. Moreover, the SP-induced depigmentation response did not be occur in 5-htr1aa zebrafish embryos. Taken together, the results of our systemic study increases our knowledge of the roles of NK1R and 5-HT1AR in melanogenesis and provides possible, novel therapeutic strategies for treatment of skin hypo/hyperpigmentation.-Wu, H., Zhao, Y., Huang, Q., Cai, M., Pan, Q., Fu, M., An, X., Xia, Z., Liu, M., Jin, Y., He, L., Shang, J. NK1R/5-HT1AR interaction is related to the regulation of melanogenesis.
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http://dx.doi.org/10.1096/fj.201700564RRDOI Listing
June 2018

Interleukin-22 participates in the inflammatory process of vitiligo.

Oncotarget 2017 Dec 24;8(65):109161-109174. Epub 2017 Nov 24.

School of Traditional Chinese Pharmacy, China Pharmaceutical University, NanJing 2111198, P.R. China.

Vitiligo is an acquired depigmentary skin inflammatory disorder. The pathogenesis of inflammatory skin disease involves the release of cytokines from keratinocytes, including interleukin (IL)-1β. IL-22 belongs to a family of cytokines structurally related to IL-10, including IL-19, IL-20, IL-24, and IL-26. In contrast to IL-10, IL-22 has proinflammatory activities. Among skin cell populations only keratinocytes are the major targets of IL-22. In the present study, we demonstrated that IL-22 promoting IL-1β secretion from keratinocytes via the Reactive oxygen species (ROS)-NOD-like receptor family, pyrin domain containing 3 (NLRP3)-caspase-1 pathway. It inhibited the expression of protease-activated receptor-2 (PAR-2) of keratinocytes. However, IL-22 had no direct effect on normal human foreskin-derived epidermal melanocytes (NHEM). Considering the closely connection between keratinocytes and melanocytes, and the ability of keratinocytes to produce a plethora of cytokines, in the present work, we examined whether IL-22 could regulate melanocytes functions by keratinocytes participation. Keratinocytes were exposed to IL-22 and the conditional medium was collected. The effect of conditional medium on melanocytes was studied. The expressions of relative proteins were assessed by western blot. Influence of conditional medium on NHEM migration was assessed by Transwell method and the apoptosis by flow cytometry analysis. The IL-22-treating keratinocytes conditional medium inhibited melanogenesis and restrained the expressions of Rab GTPases of NHEM. In addition, the conditional medium suppressed melanocytes migration and induced apoptosis. Our results collectively indicated that IL-22 may potentiate IL-1β-mediated skin inflammation and result in participating in the inflammatory pathogenesis of vitiligo.
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http://dx.doi.org/10.18632/oncotarget.22644DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5752511PMC
December 2017

Normal diet Vs High fat diet - A comparative study: Behavioral and neuroimmunological changes in adolescent male mice.

Metab Brain Dis 2018 02 3;33(1):177-190. Epub 2017 Nov 3.

State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China.

Recent evidence has established that consumption of High-fat diet (HFD)-induced obesity is associated with deficits in hippocampus-dependent memory/learning and mood states. Nevertheless the link between obesity and emotional disorders still remains to be elucidated. This issue is of particular interest during adolescence, which is important period for shaping learning/memory and mood regulation that can be sensitive to the detrimental effects of HFD. Our present study is focused to investigate behavioral and metabolic influences of short-term HFD intake in adolescent C57BL/6 mice. HFD caused weight gain, impaired glucose tolerance (IGT) and depression-like behavior as early as after 3 weeks which was clearly proved by a decrease in number of groomings in the open field test (OFT) and an increase in immobility time in the tail suspension test (TST). In the 4th week HFD induced obese model was fully developed and above behavioral symptoms were more dominant (decrease in number of crossings and groomings and increase in immobility time in both FST and TST). At the end of 6th week hippocampal analysis revealed the differences in morphology (reduced Nissl positive neurons and decreased the 5-HT receptor expression), neuronal survival (increased cleaved caspase-3 expression), synaptic plasticity (down regulation of p-CREB and BDNF), and inflammatory responses (increase in expression of pro-inflammatory cytokines and decrease in expression of anti-inflammatory cyokines) in HFD mice. Our results demonstrate that, high-fat feeding of adolescent mice could provoke "depression-like" behavior as early as 3 weeks and modulate structure, neuron survival and neuroinflammation in hippocampus as early as 6 weeks proving that adolescent age is much prone to adverse effects of HFD, which causes obesity, behavioral differences, memory and learning deficiencies.
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http://dx.doi.org/10.1007/s11011-017-0140-zDOI Listing
February 2018

Surface soil phytoliths as vegetation and altitude indicators: a study from the southern Himalaya.

Sci Rep 2015 Oct 26;5:15523. Epub 2015 Oct 26.

Key Laboratory of Cenozoic Geology and Environment, Institute of Geology and Geophysics, Chinese Academy of Sciences, Beijing 100029, China.

Phytoliths represent one of the few available altitudinal vegetation proxies for mountain ecosystems. This study analyzed 41 topsoil phytolith samples collected from five altitudinal zones in the southern Himalaya as far as, and beyond, the timberline, from tropical forest (up to 1,000 m a.s.l.) to subtropical forest (1,000-2,000 m a.s.l.), to temperate forest (2,000-3,000 m a.s.l.), to subalpine forest (3,000-4,100 m a.s.l.) and finally to alpine scrub (4,100-5,200 m a.s.l.). The statistical results show a good correlation between phytolith assemblages and these five altitudinal vegetation zones: the five phytolith assemblages identified effectively differentiated these five altitudinal vegetation zones. In particular, coniferous phytoliths accurately indicated the timberline. Additionally, we tested the phytolith index Ic (a proxy for estimating the percentage of Pooideae vis-à-vis the total grass content) as a quantifier of phytolith variety versus altitude. Ic increased along altitude, as expected. An investigation of phytoliths provided an initial basis for the analysis of the composition of gramineous vegetation. Furthermore, redundancy analysis and discriminant analysis also suggested a significant correlation between phytolith assemblages and altitude. Our research therefore provides an up-to-date analogue for the reconstruction of changes to palaeovegetation and palaeoaltitude in mountainous areas.
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http://dx.doi.org/10.1038/srep15523DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4620457PMC
October 2015

Tunable graphene-silicon heterojunctions for ultrasensitive photodetection.

Nano Lett 2013 Mar 5;13(3):909-16. Epub 2013 Feb 5.

Department of Physics, Northeastern University, Boston, Massachusetts 02115, United States.

We present the photodetection properties of graphene/Si heterojunctions both in the photocurrent and photovoltage modes. Monolayer graphene/Si junctions were found to be excellent weak-signal detectors with photovoltage responsivity exceeding 10(7) V/W and with noise-equivalent-power reaching ∼1 pW/Hz(1/2), potentially capable of distinguishing materials with transmittance, T = 0.9995 in a 0.5 s integration time. In the photocurrent mode, the response was found to remain linear over at least six decades of incident power (P), with tunable responsivity up to 435 mA/W (corresponding to incident photon conversion efficiency (IPCE) > 65%) obtained by layer thickening and doping. With millisecond-scale responses and ON/OFF ratios exceeding 10(4), these photodiodes are highly suitable for tunable and scalable broadband (400 < λ < 900 nm) photodetectors, photometers, and millisecond-response switching, spectroscopic and imaging devices, and further, and are architecturally compatible with on-chip low-power optoelectronics.
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http://dx.doi.org/10.1021/nl303682jDOI Listing
March 2013

Optical and sensing properties of 1-pyrenecarboxylic Acid-functionalized graphene films laminated on polydimethylsiloxane membranes.

ACS Nano 2011 Feb 13;5(2):1003-11. Epub 2011 Jan 13.

Department of Physics, Northeastern University, Boston, Massachusetts 02115, USA.

We present fabrication and characterization of macroscopic thin films of graphene flakes, which are functionalized with 1-pyrenecarboxylic acid (PCA) and are laminated onto flexible and transparent polydimethylsiloxane (PDMS) membranes. The noncovalently (π-stacked) functionalization of PCA allows us to obtain a number of unique optical and molecular sensing properties that are absent in pristine graphene films, without sacrificing the conducting nature of graphene. The flexible PCA-graphene-PDMS hybrid structure can block 70-95% of ultraviolet (UV) light, while allowing 65% or higher transmittance in the visible region, rendering them potentially useful for a number of flexible UV absorbing/filtering applications. In addition, the electrical resistance of these structures is found to be sensitive to the illumination of visible light, atmospheric pressure change, and the presence of different types of molecular analytes. Owing to their multifunctionality, these hybrid structures have immense potential for the development of versatile, low-cost, flexible, and portable electronic and optoelectronic devices for diverse applications.
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http://dx.doi.org/10.1021/nn102415cDOI Listing
February 2011

Stable aqueous dispersions of noncovalently functionalized graphene from graphite and their multifunctional high-performance applications.

Nano Lett 2010 Nov 17;10(11):4295-301. Epub 2010 Jun 17.

Department of Physics, Applied Physics and Astronomy, Rensselaer Polytechnic Institute, Troy, New York 12180, USA.

We present a scalable and facile technique for noncovalent functionalization of graphene with 1-pyrenecarboxylic acid that exfoliates single-, few-, and multilayered graphene flakes into stable aqueous dispersions. The exfoliation mechanism is established using stringent control experiments and detailed characterization steps. Using the exfoliated graphene, we demonstrate highly sensitive and selective conductometric sensors (whose resistance rapidly changes >10,000% in saturated ethanol vapor), and ultracapacitors with extremely high specific capacitance (∼ 120 F/g), power density (∼ 105 kW/kg), and energy density (∼ 9.2 Wh/kg).
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http://dx.doi.org/10.1021/nl903557pDOI Listing
November 2010

Highly aligned scalable platinum-decorated single-wall carbon nanotube arrays for nanoscale electrical interconnects.

ACS Nano 2009 Sep;3(9):2818-26

Department of Electrical & Computer Engineering, Northeastern University, Boston, MA 02115, USA.

We present the fabrication and characterization of nanoscale electrical interconnect test structures constructed from aligned single-wall carbon nanotubes using a template-based fluidic assembly process. This CMOS-friendly process enables the formation of highly aligned parallel nanotube interconnect structures on SiO(2)/Si substrates of widths and lengths that are limited only by lithographical limits and, hence, can be easily integrated onto existing Si-based platforms. These structures can withstand current densities of approximately 10(7) A.cm(-2), comparable or better than copper at similar dimensions. Both the nanotube alignment and failure current density improve with decreasing structure width. In addition, we present a novel Pt nanocluster decoration method that drastically decreases the resistivity of the test structures. Ab initio density functional theory calculations indicate that the increase in conductivity of the nanotubes is caused by an increase in conduction channels close to their Fermi levels due to the platinum nanocluster decoration, with a possible conversion of the semiconducting single-wall carbon nanotubes into metallic ones. These results reflect a huge step toward the proposed replacement of copper-based interconnects with carbon nanotubes at gigascale integration levels.
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http://dx.doi.org/10.1021/nn9007753DOI Listing
September 2009

Electrochemical synthesis of metal and semimetal nanotube-nanowire heterojunctions and their electronic transport properties.

Chem Commun (Camb) 2007 May 8(17):1733-5. Epub 2007 Feb 8.

Key Laboratory of Materials Physics, Anhui Key Laboratory of Nanomaterials and Nanostructures, Institute of Solid State Physics, Chinese Academy of Sciences, Hefei, 230031, China.

Metal and semimetal nanotube-nanowire heterojunction arrays have been achieved by sequential electrochemical-deposition inside the nanochannels of anodic aluminium oxide template with a layer of Au thin enough to leave the pores open.
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http://dx.doi.org/10.1039/b614147aDOI Listing
May 2007

SiO2 nanowires growing on hexagonally arranged circular patterns surrounded by TiO2 films.

J Phys Chem B 2006 Jan;110(1):222-6

Key Laboratory of Materials Physics, and Anhui Key Laboratory of Nanomaterials and Nanostructures, Institute of Solid State Physics, Chinese Academy of Sciences, Hefei 230031, PR China.

An effective approach has been demonstrated for the synthesis of novel composite architectures, SiO2 nanowires (NWs) growing on hexagonally arranged circular patterns surrounded by TiO2 films on Si substrate. First, a solution-dipping template strategy is used to create TiO2 films with hexagonally arranged pores on Au-coated Si substrate, resulting in hexagonally arranged circular patterns of catalysts surrounded by TiO2 films. Then the patterned catalysts guide the growth of SiO2 NWs with the original TiO2 films preserved, realizing the composite structures. Such composite architectures combine the photoluminescence (PL) properties of the two components, and also present more favorable PL property, laying a foundation for future advanced nano-optoelectronic devices.
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http://dx.doi.org/10.1021/jp055463bDOI Listing
January 2006