Fang Liu

Second Military Medical University, Shanghai, Shanghai, Shanghai Shi, China

Are you Fang Liu?

Claim your profile

Publications (51)185.97 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Atrial fibroblasts and macrophages have long been thought to participate in atrial fibrillation (AF). However, which specific mediator may regulate the interaction between them remains unclear. We provided the evidence for the involvement of Toll/IL-1 receptor domain-containing adaptor inducing IFN-β (TRIF), an important inflammation-related molecule, in the pathophysiology of AF. Patients with AF showed higher levels of angiotensin II (AngII) and TRIF expression and larger number of macrophages infiltration in left atria appendage than individuals with sinus rhythm (SR). In the cell study, AngII induced chemokines expressions in mouse atrial fibroblasts and AngII-stimulated atrial fibroblasts induced the chemotaxis of macrophages, which were reduced by losartan and TRIF siRNA. Meanwhile, AngII-stimulated atrial fibroblasts proliferation was enhanced by macrophages. Our data demonstrated that TRIF may be a crucial factor promoting the interaction between atrial fibroblasts and macrophages, leading to atrial fibrosis. Copyright © 2015. Published by Elsevier Inc.
    Biochemical and Biophysical Research Communications 06/2015; DOI:10.1016/j.bbrc.2015.05.131 · 2.28 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Effective repair of peripheral nerve defects is difficult because of the slow growth of new axonal growth. We propose that “neural-like cells” may be useful for the protection of peripheral nerve destructions. Such cells should prolong the time for the disintegration of spinal nerves, reduce lesions, and improve recovery. But the mechanism of neural-like cells in the peripheral nerve is still unclear. In this study, bone marrow-derived neural-like cells were used as seed cells. The cells were injected into the distal end of severed rabbit peripheral nerves that were no longer integrated with the central nervous system. Electromyography (EMG), immunohistochemistry, and transmission electron microscopy (TEM) were employed to analyze the development of the cells in the peripheral nerve environment. The CMAP amplitude appeared during the 5th week following surgery, at which time morphological characteristics of myelinated nerve fiber formation were observed. Bone marrow-derived neural-like cells could protect the disintegration and destruction of the injured peripheral nerve.
    Stem cell International 01/2015; 2015:1-9. DOI:10.1155/2015/941625 · 2.81 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Unlike Western medicine that generally uses purified compounds and aims to target a single molecule or pathway, traditional Chinese medicine (TCM) compositions usually comprise multiple herbs and components that are necessary for efficacy. Despite the very long-time and wide-spread use of TCM, there are very few direct comparisons of TCM and standard cytotoxic chemotherapy. In the present report, we compared the efficacy of the TCM herbal mixture LQ against lung cancer in mouse models with doxorubicin (DOX) and cyclophosphamide (CTX). LQ inhibited tumor size and weight measured directly as well as by fluorescent-protein imaging in subcutaneous, orthotopic, spontaneous experimental metastasis and angiogenesis mouse models of lung cancer. LQ was efficacious against primary and metastatic lung cancer without weight loss and organ toxicity. In contrast, CTX and DOX, although efficacious in the lung cancer models caused significant weight loss, and organ toxicity. LQ also had anti-angiogenic activity as observed in lung tumors growing in nestin-driven green fluorescent protein (ND-GFP) transgenic nude mice, which selectively express GFP in nascent blood vessels. Survival of tumor-bearing mice was also prolonged by LQ, comparable to DOX. In vitro, lung cancer cells were killed by LQ as observed by time-lapse imaging, comparable to cisplatinum. LQ was more potent to induce cell death on cancer cell lines than normal cell lines unlike cytotoxic chemotherapy. The results indicate that LQ has non-toxic efficacy against metastatic lung cancer.
    PLoS ONE 10/2014; 9(10):e109814. DOI:10.1371/journal.pone.0109814 · 3.53 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: BackgroundCD4+ T cell is acknowledged as a key factor in the initiation phase of liver ischemia reperfusion injury. The purpose of current study is to demonstrate the effect of antecedent near-term anti-CD25 monoclonal antibody treatment on IR-induced liver injury by modulation of CD4+ T cells.Methods70% liver warm IR was induced in male C57BL/6 mice after anti-CD25 mAb or non-specific IgG administration. Liver function, histological damage, in vitro Proliferation, FACS, cytokine production, and immunofluorescence were assessed to evaluate the impact of antecedent near-term PC61 treatment on IR-induced liver injury.ResultsAfter 70% liver ischemia, mice preconditioned with PC61 displayed significantly preserved liver function as characterized by less histological damage and reduced serum enzymes level. Mechanistic studies revealed that the protection effect of anti-CD25 mAb was associated with ameliorated intrahepatic inflammatory milieu and reduced CD4+ T lymphocytes as manifested by the decrease of proinflammatory cytokine production (less expression of TNF-α, IFN-γ, IL-2, and IL-6) and the lower CD4/CD8 proportion.ConclusionsOur results provide first line of evidence indicating that near-term treatment with anti-CD25 monoclonal antibody might provide protection for livers against IR-induced injury by reducing CD4+ T cells, but not influencing functional Treg population. Therefore, our results demonstrate a potential function of anti-CD25 monoclonal antibody which was neglected in the past, and may be helpful in various clinical conditions, particularly in liver and kidney transplantations.
    PLoS ONE 09/2014; 9(9):e106892. DOI:10.1371/journal.pone.0106892 · 3.53 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The exact mechanisms underlying inhibitory effects of pioglitazone (Pio) on Angiotensin II (AngII)-induced atrial fibrosis are complex and remain largely unknown. In the present study, we examined the effect of Pio on AngII-induced mice atrial fibrosis in vivo and atrial fibroblasts proliferation in vitro. In vivo study showed that AngII infusion induced atrial fibrosis and increased expressions of Toll/IL-1 receptor domain-containing adaptor inducing IFN-β (TRIF) and tumor necrosis factor receptor associated factor 6 (TRAF6) in mice models. However, those effects could be attenuated by Pio (P<0.01). As for in vitro experiment, Pio suppressed AngII-induced atrial fibroblasts proliferation via nuclear factor-κB/transforming growth factor-β1/TRIF/TRAF6 signaling pathway in primary cultured mice atrial fibroblasts (P<0.01). In conclusion, suppression of Pio on AngII-induced atrial fibrosis might be related with its inhibitory effects on above signaling pathway.
    Experimental Cell Research 08/2014; 330(1). DOI:10.1016/j.yexcr.2014.08.021 · 3.37 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background & Aims: The mechanisms of glycogen synthase kinase-3 (GSK-3)-mediated cytoprotection during liver ischemia/reperfusion (I/R) remain controversial, particularly in older organs. This study explores the role and potential mechanisms of GSK-3 in young and aging livers. Methods: A rodent partial warm I/R model was used to evaluate the therapeutic potential of GSK-3 modulation during hepatic I/R in young and aging Sprague-Dawley rats. Results: GSK-3 inhibition through IPC or SB216763 (SB21) preconditioning protected young rats from I/R-induced liver injury. This protection was absent in old animals but could be restored by glucose infusion prior to the I/R insult. The protection conferred by GSK-3 inhibition depended on mitochondrial metabolism regulation. Indeed, the inhibition of GSK-3 suppressed mitochondrial permeability transition pore (MPTP) opening, triggering mitohormesis in young animals, whereas insufficient fuel suppressed mitochondrial metabolism and inactivated the GSK-3-related protection in old animals. SB21 and glucose reactivated the mitochondrial F0F1-ATPase and subsequent protective cascades in the senescent liver. These effects were antagonized by an ATPase inhibitor and by an MPTP opener. Conclusions: The protection conferred by GSK-3 inhibition during hepatic I/R insult is energy dependent, particularly in senescent livers. These findings demonstrate a key role for GSK-3-related mitochondrial energy homeostasis, which may shed new light on the clinical use of GSK-3 inhibitors to protect liver function in surgical settings, particularly for older patients.
    Journal of Hepatology 05/2014; 61(4). DOI:10.1016/j.jhep.2014.05.017 · 10.40 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Abstract Studies have showed that transplanted stem cells in inner ear won't regenerate to replace the damaged sensory hair cells. They can spontaneously differentiate into mesenchymal cells and fibrocytes in the damaged inner ear. Only mature sensory cells of MSCs-derived possess the great potency for cell transplantation in the treatment of sensorineural hearing loss. So, we try to establish an efficient generation of the glutamatergic sensory neural phenotype for the cell transplantation of the hearing loss. We isolated MSCs from femoral and tibial bones according to their adherence to culture dishes. After purification, proliferation, and passaged, cells became homogeneous in appearance, showing more uniform and grew in a monolayer with a typical spindle-shape morphology.The cell surface markers were assessed using FACS to characterize the isolated cells. For neural induction to harvest the glutamatergic sensory neurons, passage 3 MSCs were incubated with preinduced medium for 24 hours, neural induced medium for an additional 14 days. The cells exhibite a typical neural shape. RT-PCR analysis indicated that the mRNA levels of the neural cell marker nestin, Tau, MAP-2, β-tubulin Ⅲ, GluR-3 and GluR-4 were higher compared with primary MSCs. Immunohistochemistry and western-blotting proofed that nestin, MAP-2, β-tubulin Ⅲ and GluR-4 proteins indeed exhibit their expression difference in the induced cells compare to the MSCs. We show an efficient protocol by the combined applications of Sonic Hedgehog (Shh) and Retinoic Acid (RA) to induce MSCs to differentiate into the glutamatergic sensory neuron which were identified from the morphological, biochemical and molecular characteristics.
    Journal of Immunoassay and Immunochemistry 02/2014; 36(1). DOI:10.1080/15321819.2014.889025 · 0.73 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: It has been well proved that acute inflammatory response and hepatocellular apoptosis contributed to the pathogenesis of liver ischemia reperfusion (IR) injury. A vast amount of research has demonstrated that magnesium lithospermate B (MLB) has potent anti-apoptosis and potential anti-inflammatory pharmacological properties. However, it has not previously been examined whether MLB can attenuate hepatic IR injury. Firstly, the optimal dose of MLB to protect against hepatic IR injury was determined using hepatic IR model in mice. Then, the effect of MLB on IR-induced inflammatory response was detected in detail. We found that MLB exhibited protective effect from the beginning of 50 mg/kg and culminated at the doses of 100 and 200 mg/kg. The alanine aminotransferase and aspartate aminotransferase levels in MLB group were markedly decreased. Severe hepatocellular swelling/necrosis, sinusoidal/vascular congestion and inflammatory cell infiltration were seen and a large number of apoptotic cells were found in the liver samples from Saline group, while minimal damage and very few apoptotic cells were noted in the samples from MLB group. Kuppfer cells infiltration, myeloperoxidase activity and mRNA level of CD11b in MLB group was significantly decreased. Serum TNF-a and IL-6, and mRNA expression of CXCL-10 and ICAM-1 was markedly decreased in the samples from MLB group. Inflammatory signaling pathway activation was largely prevented in MLB group. MLB can significantly attenuate IR-induced hepatocellular damage and hepatocellular apoptosis by preventing inflammatory signaling pathways activation, inflammatory mediators expression and macrophage and neutrophil infiltration.
    Cell biochemistry and biophysics 01/2014; 69(2). DOI:10.1007/s12013-013-9806-2 · 2.38 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Previously, we demonstrated that Tim-1-Fc prevents acute cardiac graft rejection by inhibiting Th1 response. In the present report, we tackled the impact of Tim-1-Fc on Th17 cells in a model of cardiac chronic rejection. Administration of Tim-1-Fc did not result in a detectable impact on innate immunity and regulatory T cells, while it provided protection for Bm12-derive cardiac grafts against chronic rejection in B6 recipients, as manifested by the reduction of inflammatory infiltration along with less severity of vasculopathy. Studies in T-bet(-/-) recipients by implanting Bm12-derived cardiac grafts further revealed that Tim-1-Fc significantly protected cardiac grafts from chronic rejection along with attenuated production of IL-17 producing T cells. Depletion of CD4 and CD8 T cells or blockade of IL-17 in T-bet(-/-) recipients demonstrated that Tim-1-Fc selectively suppresses Th17 differentiation along with attenuated IL-17 secretion. Together, our data suggest that Tim-1-Fc protects cardiac grafts from chronic rejection by suppressing CD4 Th17 development and functionality. Therefore, Tim-1-Fc might be a potential immunosuppressive agent in the setting of cardiac transplantation.
    International journal of clinical and experimental pathology 01/2014; 7(2):509-20. · 1.78 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Previously, we observed that mir-155 is induced during dendritic cell (DC) differentiation. We now demon-strated convincing evidence indicating that mir-155 promotes DC maturation and regulates its capacity for antigen presentation and induction of alloreactive T cell activation. Interestingly, the induction of miR-155 expression in DCs is dependent on the TLR4/Myd88/NF-κB signaling. Our mechanistic studies further revealed that SOCS1 is a direct target for mir-155, and by binding to its 3'UTR, mir-155 is likely to affect SOCS1 translation. Suppression of mir-155 expression in DCs significantly attenuated LPS-induced DC maturation along with reduced capability to stimulate allogeneic T cell proliferation. As a result, administration of antagomiR-155 provided protection for cardiac allografts from rejection. Together, our data support that suppression of miR-155 in DCs could be a viable therapeutic strategy for prevention and treatment of allograft rejection in clinical setting of transplantation.
    International Journal of Clinical and Experimental Medicine 01/2014; 7(11):4572-83. · 1.42 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: It has been demonstrated that atrial remodeling contributes toward atrial fibrillation(AF) maintenance and angiotensin II(AngII) is involved in the pathogenesis of atrial remodeling. Peroxisome proliferator-activated receptor-γ(PPAR-γ) agonists have been shown to inhibit atrial remodeling. However, the underlying mechanisms are poorly understood. In the present study we investigated the regulating effects of PPAR-γ agonist on AngII-induced atrial structural and electrical remodeling in vitro cellular models. The effects of piogliazone on AngII-induced connective tissue growth factor(CTGF) expression and cell proliferation were assessed in primary-cultured mouse atrial fibroblasts. The influences of pioglitazone on AngII-induced L-type calcium channel(ICa-L) α1c expression and current density were evaluated in atrial myocytes (HL-1). Pioglitazone attenuated AngII-induced CTGF expression and proliferation in atrial fibroblasts. And pioglitazone also inhibited the expression or phosphorylation of AngII-induced transforming growth factor-β1(TGF-β1), tumor necrosis factor receptor associated factor 6(TRAF6), TGF-β-associated kinase 1(TAK1) and Smad2/3. In HL-1 cells, pioglitazone suppressed AngII-induced ICa-L α1c expression and current density as well as CAMP responsive element binding protein(CREB) phosphorylation. Besides, pioglitazone inhibited AngII-induced production of AngII type I receptor(AT1R) and downregulation of PPAR-γ in both atrial fibroblasts and HL-1 cells. Pioglitazone suppresses AngII-induced CTGF expression and proliferation in atrial fibroblasts, which might be at least in part related with its inhibitory effects on TGF-β1/Smad2/3 and TGF-β1/TRAF6/TAK1 signaling pathways. Moreover, pioglitazaone also attenuates AngII-induced ICa-L remodeling in HL-1 cells, which might be at least in part associated with its inhibitory effect on CREB phosphorylation. It is suggested that PPAR-γ agonist may have potential applications in preventing atrial remodeling.
    Journal of Molecular and Cellular Cardiology 10/2013; 65. DOI:10.1016/j.yjmcc.2013.09.016 · 5.22 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: We have previously shown that nestin-expressing hair follicle cells from the mouse and human are multipotent and can differentiate into many cell types, including neurons and glial cells and can effect nerve and spinal cord repair upon transplantation in mouse models. In the present study, nestin-expressing hair follicle cells expressing red fluorescent protein (RFP) were induced by retinoic acid and fetal bovine serum to differentiate and then transplanted together with Matrigel into the transected distal sciatic or tibial nerve stump of transgenic nude mice ubiquitously expressing GFP. Control mice were transplanted with Matrigel only. The transplanted cells appeared neuron-like, with large round nuclei and long extensions. Immunofluorescence staining showed that some of the transplanted cells in the distal nerve stump expressed the neuron marker Tuj1 as well as motor neuron markers Isl 1/2 and EN1. These transplanted cells contacted each other as well as host nerve fibers. Two weeks post-transplantation, nerve fibers in the distal sciatic nerve stump of the transplanted mice had greater expression of motor neuron markers and neurotrophic factor 3 (NT-3) than those in the Matrigel-only transplanted mice. Muscle fiber areas in the nestin-expressing stem-cell plus Matrigel transplanted animals were much bigger than that in the Matrigel-only transplanted animals after four weeks. The present results suggest that transplanted nestin-expressing hair follicle cells can differentiate into motor neurons and reduce muscle atrophy after sciatic nerve transection. This study demonstrates a new and accessible neuron source to reduce muscle atrophy after nerve injury.
    Tissue Engineering Part A 09/2013; DOI:10.1089/ten.TEA.2012.0657 · 4.64 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Antibody-mediated rejection (AMR) is gaining increasing recognition as a critical causative factor contributing to graft loss in organ transplantation. However, current therapeutic options for prevention and treatment of AMR are very limited and ineffective. The impact of epigenetic modification in B-cell function and its involvement in AMR is still yet to be explored. The impacts of suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor, on isolated murine B-cell viability, proliferation, apoptosis, expression of surface marker, and secretion of immunoglobulin and interleukin-10 were investigated. In vivo, a murine cardiac transplant model was used to evaluate the effect of SAHA on splenic B-cell subsets and on AMR in Rag1 recipient mice after reconstitution of allostimulated B cells. SAHA possesses capability to repress B-cell function. Specifically, SAHA is potent to decrease the viability of isolated B cells by inducing apoptosis. SAHA was also found capable of suppressing the expression of B-cell costimulatory molecules and, as a result, addition of SAHA into the cultures attenuated B-cell proliferation and immunoglobulin secretion. In line with these results, administration of SAHA significantly suppressed AMR in Rag1 recipient mice after reconstitution of allostimulated B cells along with enhanced cardiac allograft survival time. Mechanistic studies revealed that SAHA promotes B-cell secretion of interleukin-10. Our data support that SAHA could be a promising immunosuppressive agent with potential beneficial effect on prevention and treatment of AMR.
    Transplantation 08/2013; 96(6). DOI:10.1097/TP.0b013e31829b7bfc · 3.78 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: We have previously reported that nestin-expressing hair follicle stem cells can differentiate into neurons, Schwann cells, and other cell types. In the present study, vibrissa hair follicles, including their sensory nerve stump, were excised from transgenic mice in which the nestin promoter drives green fluorescent protein (ND-GFP), and were placed in 3D culture supported by Gelfoam®. β-III tubulin-positive fibers, consisting of ND-GFP-expressing cells extended up to 500 µm from the whisker nerve stump in histoculture. The gorwing fibers had growth cones on their tips expressing F-actin. These findings indicate that β-III tubulin-positive fibers elongating from the whisker follicle sensory nerve stump were growing axons. The growing whisker sensory nerve was highly enriched in ND-GFP cells which appeared to play a major role in its elongation and interaction with other nerves in 3D culture, including the sciatic nerve, the trigeminal nerve, and the trigeminal nerve ganglion. The results of the present report suggest a major function of the nestin-expressing stem cells in the hair follicle is for growth of the follicle sensory nerve. J. Cell. Biochem. © 2013 Wiley Periodicals, Inc.
    Journal of Cellular Biochemistry 07/2013; 114(7). DOI:10.1002/jcb.24509 · 3.37 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Pancreatic cancer is highly treatment-resistant and has one of the highest fatality rates of all cancers and is the fourth highest cancer killer worldwide. Novel, more effective strategies are needed to treat this disease. We report here on the use of patient-like orthotopic nude-mouse models of human metastatic pancreatic cancer to compare the traditional Chinese medicine (TCM) herbal mixture LQ to gemcitabine, which is first-line therapy for this disease, for anti-metastatic and anti-tumor activity as well as safety. The human pancreatic cancer cell line, MiaPaCa-2, labeled with red fluorescent protein (RFP), was used for the orthotopic model. LQ (gavage, 600 mg/kg/day) significantly inhibited pancreatic cancer tumor growth and metastasis, as measured by imaging, with no overt toxicity. Survival of tumor-bearing mice was also prolonged by LQ treatment. The therapeutic efficacy of LQ is comparable with gemcitabine but with less toxicity, as indicated by a lack of body-weight loss with LQ, but not gemcitabine. The results indicate that TCM can have non-toxic efficacy against metastatic pancreatic cancer comparable to gemcitabine in a clinically-relevant orthotopic mouse model of cancer and that TCM can have an important role in the treatment of pancreatic cancer. J. Cell. Biochem. © 2013 Wiley Periodicals, Inc.
    Journal of Cellular Biochemistry 04/2013; DOI:10.1002/jcb.24561 · 3.37 Impact Factor
  • Journal of Dermatological Science 02/2013; 69(2):e60. DOI:10.1016/j.jdermsci.2012.11.484 · 3.34 Impact Factor
  • Journal of Dermatological Science 02/2013; 69(2):e60. DOI:10.1016/j.jdermsci.2012.11.483 · 3.34 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Sinomenine (SIN) is a purified alkaloid from the Chinese herb Sinomenium acutum. Previous studies demonstrated that SIN possesses anti-inflammatory and anti-apoptotic properties. We thus in the present report conducted studies to examine its impact on ischemia reperfusion (IR) induced renal injury. Precondition of mice with 200 mg/kg of SIN provided significant protection for mice against IR-induced renal injury as manifested by the attenuated serum creatinine (Cre) and blood urea nitrogen (BUN) along with less severity for histological changes and tubular cell apoptosis. In line with these results, treatment of mice with SIN suppressed IR-induced inflammatory infiltration and the expression of chemokine CXCL-10, adhesion molecule ICAM-1, and cytokines TNF-а/IL-6. Mechanistic studies revealed that SIN inhibits NF-κB transcriptional activity to suppress IR-induced inflammatory response in the kidney, while it attenuates MAP kinase signaling to prevent tubular cells undergoing apoptosis after IR insult. Altogether, our data support that SIN could be a useful therapeutic agent for prevention and treatment of IR-induced renal injury in the clinical settings.
    International journal of clinical and experimental pathology 01/2013; 6(9):1702-12. · 1.78 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Suberoylanilide hydroxamic acid (SAHA), as a histone deacetylase (HDAC) inhibitor (HDACi), was recently found to exhibit an immunosuppressive effect. However, whether SAHA can synergize with calcineurin inhibitors (CNIs) to inhibit allograft rejection and its underlying mechanism remain elusive. In this study, we demonstrated the synergistic effects of SAHA and non-therapeutic dose of tacrolimus (FK506) in prolonging the allograft survival in a murine cardiac transplant model. Concomitant intragraft examination revealed that allografts from SAHA-treated recipients showed significantly lower levels of IL-17 expression, and no discernable difference for IL-17 expressions was detected between SAHA- and SAHA/FK506-treated allograft as compared with allografts from FK506-treated animals. In contrast, administration of FK506 significantly suppressed interferon (IFN)-γ but increased IL-10 expression as compared with that of SAHA-treated animals, and this effect was independent of SAHA. Interestingly, SAHA synergizes with FK506 to promote Foxp3 and CTLA4 expression. In vitro, SAHA reduced the proportion of Th17 cells in isolated CD4⁺ T-cell population and decreased expressions of IL-17A, IL-17F, STAT3 and RORγt in these cells. Moreover, SAHA enhances suppressive function of regulatory T (Treg) cells by upregulating the expression of CTLA-4 without affecting T effector cell proliferation, and increased the proportion of Treg by selectively promoting apoptosis of T effector cells. Therefore, SAHA, a HDACi, may be a promising immunosuppressive agent with potential benefit in conjunction with CNI drugs.
    Cellular & molecular immunology 08/2012; 9(5):390-8. DOI:10.1038/cmi.2012.28 · 4.19 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Flurbiprofen acts as a nonselective inhibitor for cyclooxygenases (COX-1 and COX-2), but its impact on hepatic ischemia/reperfusion (I/R) injury remains unclear. Mice were randomized into sham, I/R and flurbiprofen (Flurb) groups. The hepatic artery and portal vein to the left and median liver lobes were occluded for 90 min and unclamped for reperfusion to establish a model of segmental (70%) warm hepatic ischemia. Pretreatment of animals with flurbiprofen prior to I/R insult significantly decreased serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH), and prevented hepatocytes from I/R-induced apoptosis/necrosis. Moreover, flurbiprofen dramatically inhibited mitochondrial permeability transition (MPT) pore opening, and thus prevented mitochondrial-related cell death and apoptosis. Mechanistic studies revealed that flurbiprofen markedly inhibited glycogen synthase kinase (GSK)-3β activity and increased phosphorylation of GSK-3β at Ser9, which, consequently, could modulate the adenine nucleotide translocase (ANT)-cyclophilin D (CyP-D) complex and the susceptibility to MPT induction. Therefore, administration of flurbiprofen prior to hepatic I/R ameliorates mitochondrial and hepatocellular damage through inhibition of MPT and inactivation of GSK-3β, and provides experimental evidence for clinical use of flurbiprofen to protect liver function in surgical settings in addition to its conventional use for pain relief.
    Molecular Medicine 06/2012; 18(1):1128-35. DOI:10.2119/molmed.2012.00088 · 4.82 Impact Factor

Publication Stats

210 Citations
185.97 Total Impact Points


  • 2007–2015
    • Second Military Medical University, Shanghai
      • • Department of Spine Surgery
      • • Department of Anesthesiology
      • • Department of Military Hygienics
      Shanghai, Shanghai Shi, China
  • 2013
    • Changhai Hospital, Shanghai
      Shanghai, Shanghai Shi, China
  • 2012
    • Shanghai University of Traditional Chinese Medicine
      Shanghai, Shanghai Shi, China
  • 2010
    • University of California, San Diego
      • Department of Surgery
      San Diego, California, United States