Xiang Gao

Chinese Academy of Sciences, Peping, Beijing, China

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Publications (19)67.47 Total impact

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    ABSTRACT: Fluoro-functionalized polymeric ionic liquids (F-PILs) with imidazolium cations and bromide or chloride anions were designed for cycloaddition reactions of CO2 with epoxides. It was found that the fluorine content in F-PILs significantly influenced the catalytic activity of the catalysts, and F-PIL-Br showed three times higher activity for CO2 reacting with styrene oxide than non-fluorous PIL-Br. Moreover, F-PIL-Br could be extended to catalyse a broad range of reactants under 1 MPa CO2 pressure, producing a series of cyclic carbonates in excellent yields (93–99%). In addition, it showed high stability and easy recyclability.
    Green Chemistry 07/2014; 16(8). · 6.83 Impact Factor
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    ABSTRACT: Unlike native high-density lipoprotein (HDL), oxidized HDL exerts adverse effects in a number of diseases, including chronic kidney disease (CKD); however, the mechanisms involved in this process remain unclear. In the present study, we investigated the effects of oxidized HDL on renal tubular cells, which play an important role in the progression of CKD. Human renal proximal tubule epithelial cells (HK-2) were cultured and stimulated with various concentrations of oxidized HDL in the absence or presence of CD36 siRNA. The results revealed that oxidized HDL enhanced the production of reactive oxygen species (ROS) and upregulated the expression of pro-inflammatory factors in the HK-2 cells in a dose-dependent manner. Incubation with oxidized HDL also increased the apoptosis of the HK-2 cells and reduced their migration ability in a dose‑dependent manner. Src family kinase, mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) were activated following stimulation with oxidized HDL. All these effects mediated by oxidized HDL on HK-2 cells were markedly attenuated by transfection with with CD36 siRNA pior to stimulation with oxidized HDL. These findings suggest that oxidized HDL enhances the pro-inflammatory properties and impairs the function of HK-2 cells, mainly through the scavenger receptor, CD36, as well as through the Src, MAPK and NF-κB pathways.
    International Journal of Molecular Medicine 06/2014; · 1.96 Impact Factor
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    ABSTRACT: The chemical fixation of CO2 under mild reaction conditions is of significance from a sustainable chemistry viewpoint. Herein a CO2-reactive protic ionic liquid (PIL), [HDBU+][TFE−], was designed by neutralization of the superbase 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) with a weak proton donor trifluoroethanol (TFE). As a bifunctional catalyst for simultaneously activating CO2 and the substrate, this PIL displayed excellent performance in catalyzing the reactions of CO2 with 2-aminobenzonitriles at atmospheric pressure and room temperature, thus producing a series of quinazoline-2,4(1H,3H)-diones in excellent yields.
    Angewandte Chemie International Edition 04/2014; · 11.34 Impact Factor
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    ABSTRACT: The chemical fixation of CO2 under mild reaction conditions is of significance from a sustainable chemistry viewpoint. Herein a CO2-reactive protic ionic liquid (PIL), [HDBU+][TFE−], was designed by neutralization of the superbase 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) with a weak proton donor trifluoroethanol (TFE). As a bifunctional catalyst for simultaneously activating CO2 and the substrate, this PIL displayed excellent performance in catalyzing the reactions of CO2 with 2-aminobenzonitriles at atmospheric pressure and room temperature, thus producing a series of quinazoline-2,4(1H,3H)-diones in excellent yields.
    Angewandte Chemie 04/2014;
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    ABSTRACT: The complement system is involved in many immune complex-mediated kidney diseases, yet its role in the pathogenesis of autosomal dominant polycystic kidney disease (ADPKD) has not been examined in detail. Screening of the glycoproteome of urine samples from ADPKD patients revealed that levels of complement factor B (CFB), serpin peptidase inhibitor, complement component 1 inhibitor (SERPING1) and complement component 9 (C9) increased whereas complement component 1, r subcomponent-like (C1RL), CD55 and CD59 levels decreased with disease progression. Immunostaining and western blot analysis confirmed the enhanced expression of CFB and C9 in cystic kidneys from ADPKD patients. Immunostaining also showed that the expressions of CFB and C9 in renal biopsy tissues from patients with other types of chronic kidney disease were lower than in tissues from ADPKD patients. The effect of the complement inhibitor rosmarinic acid (RMA) was evaluated in Pkd1(-/-) mice and Han:SPRD Cy/+ rats. Compared with vehicle-treated Pkd1(-/-) animals, RMA-treated mice had significantly lower serum creatinine (-50%) and blood urea nitrogen (-78%) levels, two kidneys/body weight ratio (-60%) and renal cystic index (-60%). Similar results were found in Cy/+ rats. Lower numbers of Ki67-positive nuclei and inflammatory cells and reduced fibrosis were observed in both animal models upon treatment with RMA. These results suggest that excessive activation of the alternative complement pathway is associated with ADPKD progression, probably mediated by cyst-lining epithelial cell proliferation, tubulointerstitial inflammatory cell infiltration and fibrosis. Targeting the complement system might represent a new therapeutic strategy for ADPKD. This article is protected by copyright. All rights reserved.
    Journal of Internal Medicine 02/2014; · 6.46 Impact Factor
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    ABSTRACT: Cyclosporine A (CsA) is an immunosuppressant agent and is utilized as a second-line drug therapy for refractory nephrotic syndrome (RNS). In general, the use of CsA is strictly controlled in patients with an estimated glomerular filtration rate (eGFR) <30-40 ml/min/1.73 m(2), and little is known about the safety and efficacy of CsA treatment in patients with RNS complicated by renal dysfunction. In the present study, the clinical data of 10 patients with RNS and renal dysfunction, who received CsA treatment between 2000 and 2009 in the Kidney Institute of PLA, were reviewed retrospectively. Pathologically, these patients included six cases with minimal change, two cases of diffuse mesangial proliferation and two cases of focal segmental glomerulosclerosis. Six months subsequent to the initiation of the CsA treatment, six patients achieved complete remission, two patients achieved remarkable remission and two patients achieved partial remission. Renal function was improved in all patients as represented by the improvement in the eGFR (28.6±3.8 ml/min/1.73 m(2) prior to treatment versus 99.3±21.9 ml/min/1.73 m(2) 6 months subsequent to treatment). Few adverse CsA-related events were observed. These results suggest that renal dysfunction is not an absolute contraindication for CsA treatment in patients with RNS. The use of CsA is safe and efficacious and may, in certain cases, improve renal function in patients with RNS and renal impairment.
    Experimental and therapeutic medicine 02/2014; 7(2):447-450. · 0.34 Impact Factor
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    ABSTRACT: Pd/C-catalyzed direct formylation of aromatic iodides to aryl aldehydes using CO2 as a C1 resource was realized for the first time in the presence of hydrosilanes and base DBU under mild conditions, giving a series of aldehydes in good yields.
    Chemical Communications 01/2014; · 6.38 Impact Factor
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    ABSTRACT: Galanin (Gal), a bioactive neuropeptide, is widely distributed throughout the central nervous system and has diverse modulatory effects. To understand the central effect of this training-stimulatory peptide on insulin sensitivity, its antagonist M35 was injected into the cerebral ventricle in type 2 diabetic rats. A treadmill running of the rats was used to stimulate circulating Gal secretion and central Gal mRNA expression. The results showed that M35 significantly decreased glucose infusion rates in euglycemic-hyperinsulinemic clamp tests as well as 2-deoxy-[(3) H]D-glucose uptake and peroxisome proliferator-activated receptor-α expression levels in skeletal muscles. M35 also attenuated glucose transporter 4 (GLUT4) concentration in plasma membranes and total cell membranes of myocytes, and the ratios of the GLUT4 contents in the former to the latter in M35 groups were lower than those of each diabetic control. These results imply that endogenous Gal, acting through its central receptor, may facilitate GLUT4 translocation from cytoplasm vesicles to cellular surface of myocytes to accelerate glucose uptake and to enhance insulin sensitivity in healthy and type 2 diabetic rats. Gal and its relative agents are potential targets for treatment of type 2 diabetes mellitus and its complications. © 2013 Wiley Periodicals, Inc.
    Journal of Neuroscience Research 05/2013; · 2.97 Impact Factor
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    ABSTRACT: Background/Aims: Renal interstitial fibrosis is a hallmark of progressive chronic kidney disease (CKD). Previous studies reported that kruppel-like factor 15 (KLF15) is an important regulator of cardiac fibrosis and could reduce the expression of extracellular matrix in mesangial cells. However, the role of this transcription factor in renal interstitial fibrosis has not been reported. Methods: In this study, we examined KLF15 expression in the remnant kidney of 5/6 nephrectomized rats 12 or 24 weeks after operation. In vitro we examined the effect of altered KLF15 expression on the production of extracellular matrix and the pro-fibrotic factor CTGF in rat renal fibroblasts (NRK-49F), and further explored the related mechanisms. Results: The level of KLF15 was drastically decreased in the renal interstitium of 5/6 nephrectomized rats with progressive interstitial fibrosis, especially at 24 weeks. Our in vitro evidence showed that overexpression of KLF15 repressed basal and transforming growth factor-β1 (TGF-β1)-induced extracellular matrix and CTGF in NRK-49F cells. In addition, TGF-β1-mediated activation of extracellular-regulated kinase (ERK) / mitogen-activated protein kinase (MAPK) and Jun N-terminal kinase (JNK) /MAPK downregulated KLF15 expression and increased the level of extracellular matrix and CTGF, and all these effects were completely abolished by ERK1/2 inhibitor and JNK inhibitor in NRK-49F cells. Conclusions: Our findings implicate that KLF15 plays an important role and may prove to be an antifibrotic factor in renal interstitial fibrosis through regulation of ERK/MAPK and JNK/MAPK signaling pathways. © 2014 S. Karger AG, Basel.
    Kidney and Blood Pressure Research 01/2013; 37(6):631-40. · 1.60 Impact Factor
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    ABSTRACT: Background and Aims: A liquid chromatography coupled with mass spectrometry based metabonomics approach was applied to investigate the protective effects of rosiglitazone (RGTZ) and caloric restriction (CR) for renal senescence in rat model. Methods: Kidney tissues and serum samples were collected from four groups of rats, including 12-month and 24-month ad libitum fed rats, RGTZ and CR treated 24-month rats. Multivariate data analysis was performed on the mass data of metabonomic profiles to detect the differences among the groups. Results: By metabolite profiling and partial least squares discriminate analysis, 23 renal senescence-related endogenous metabolites were discovered, including phospholipids, carnitine, acetylcarnitine, and creatinine, most of which were related to the oxidative stress and lipid metabolism. Conclusion: Renal senescence is characterized by oxidative stress and changes in lipid metabolism, and RGTZ administration and CR treatment may have similar protective effects for renal senescence via restraining oxidative stress and lipid metabolism.
    Aging - Clinical and Experimental Research 05/2012; · 1.01 Impact Factor
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    ABSTRACT: The incidence of acute kidney injury (AKI) is very high, and multiple physiopathological processes are involved, including endoplasmic reticulum stress (ERS). Tauroursodeoxycholic acid (TUDCA) is an endogenous bile acid derivative that has been reported to inhibit ERS. To determine whether TUDCA had a nephroprotective effect on AKI and to explore the exact mechanism, an ischaemia/reperfusion (I/R)-induced AKI mouse model and a tunicamycin-pre-treated TCMK-1 cell model were established. It was found that the renal tubular necrosis score and cell apoptosis index reached their peak 24 hr after I/R. GRP78 and C/EBP homologous protein (CHOP) expression and Caspase 12 activation were enhanced, reaching their peaks at 4 and 12 hr, respectively. TUDCA intervention not only decreased the renal tubular necrosis score and the cell apoptosis index but also down-regulated GRP78 and CHOP expression and Caspase 12 activation. The survival rate of TCMK-1 cells pre-treated with TUDCA was significantly higher than that of TCMK-1 cells without TUDCA pre-treatment. In conclusion, TUDCA had a nephroprotective effect on IR-induced AKI by inhibiting ERS and by blocking GRP78 and CHOP expression, reducing Caspase 12 activation and inhibiting cell apoptosis.
    Basic & Clinical Pharmacology & Toxicology 12/2011; 111(1):14-23. · 2.18 Impact Factor
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    ABSTRACT: While caloric restriction (CR) is associated with a prolonged lifespan in multiple species by regulating metabolism, a comprehensive profile of metabolism under CR conditions remains largely unclear. Therefore, in this study we aimed to characterize the metabolomic profiling associated with CR using a rat model. Rapid resolution liquid chromatography/electrospray ionization quadrupole-time of flight mass spectrometry (RRLC/ESI-Q-TOFMS) was employed to analyze metabolomic profiling of urine samples from aging rats who underwent caloric restriction (CR; n=7) or were provided a normal diet (N; n=8) for 12 weeks time. Multivariate data analysis was performed on the mass data of metabolomic profiles to uncover the differences between the CR and N groups. CR treatment led to manifest metabolic changes in aging rats, and fifteen urinary metabolites including hypoxanthine, hippurate, dimethylglycine and creatinine were significantly different in the rat groups. Our study demonstrates the high reliability of the HPLC-based metabolomic approach towards the study of anti-aging effects induced by CR, while the urinary metabolites we identified may become potential biomarkers of aging.
    Aging clinical and experimental research 02/2011; 24(1):79-84. · 1.01 Impact Factor
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    ABSTRACT: Dietary protein restriction is an important treatment for chronic kidney disease. Herein, we tested the effect of low-protein or low-protein plus ketoacids (KA) diet in a remnant kidney model. Rats with a remnant kidney were randomized to receive normal protein diet (22%), low-protein (6%) diet (LPD), or low-protein (5%) plus KA (1%) diet for 6 months. Protein restriction prevented proteinuria, decreased blood urea nitrogen levels, and renal lesions; however, the LPD retarded growth and decreased serum albumin levels. Supplementation with KA corrected these abnormalities and provided superior renal protection compared with protein restriction alone. The levels of Kruppel-like factor-15 (KLF15), a transcription factor shown to reduce cardiac fibrosis, were decreased in remnant kidneys. Protein restriction, which increased KLF15 levels in the normal kidney, partially recovered the levels of KLF15 in remnant kidney. The expression of KLF15 in mesangial cells was repressed by oxidative stress, transforming growth factor-β, and tumor necrosis factor (TNF)-α. The suppressive effect of TNF-α on KLF15 expression was mediated by TNF receptor-1 and nuclear factor-κB. Overexpression of KLF15 in mesangial and HEK293 cells significantly decreased fibronectin and type IV collagen mRNA levels. Furthermore, KLF15 knockout mice developed glomerulosclerosis following uninephrectomy. Thus, KLF15 may be an antifibrotic factor in the kidney, and its decreased expression may contribute to the progression of kidney disease.
    Kidney International 01/2011; 79(9):987-96. · 8.52 Impact Factor
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    ABSTRACT: Recent reports support a protective role for angiotensin-converting enzyme 2 (ACE2) against glomerular diseases, especially by decreasing of extracellular matrix (ECM) proteins. However, the mechanism regulating this effect appears to be complex and poorly understood. Our aim was to investigate whether or not ACE2 ameliorates the profibrotic effects of Ang II-mediated, Akt-dependent pathways in the mouse mesangial cell line, MES-13.Gene transfer of ACE2 suppressed Ang II-activated Akt-phosphorylation, accompanied by a decreased level of collagen type I in cells. In addition, Ang II-induced collagen type I synthesis in MES-13s by activating the Ang II/AT-1R-PI3K pathway. This transactivation was dependent on cAMP/Epac but not on PKA. TGF-βRI played a pivotal role in this signaling pathway inducing collagen deposition effects which could be reversed by ACE2 gene transfer in MES-13 cells. The results revealed that gene transfer of ACE2 regulated Ang II-mediated AT1R-TGFβRI-PI3K-Akt signaling and involved the synthesis of collagen. The beneficial effect of ACE2 overexpression appeared to result mainly from blocking phosphorylation of Akt in mesangial cells, suggesting that the ACE2 gene might be a novel therapeutic target for glomerular diseases.
    Endocrine 12/2010; 39(2):139-47. · 1.42 Impact Factor
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    ABSTRACT: Inflammation is a mechanism of glomerular damage in chronic glomerulopathies, in which dyslipidaemia plays an important role. Unlike native high-density lipoprotein (HDL), oxidized HDL is thought to be an adverse factor in chronic ischaemic disease and may increase the production of inflammatory cytokines in atheromatous plaques and plasma, but the effect of oxidized HDL on mesangial cells remains unclear. Intracellular reactive oxygen species level was measured. The inflammatory and proapoptotic effects of oxidized HDL were detected in rat mesangial cells by measuring levels of tumour necrosis factor-alpha, regulated upon activation, normal T-cell expressed and secreted, monocyte chemoattractant protein-1, CXC chemokine ligand-1 and early apoptosis. The expression of mitogen-activated protein kinase (MAPK) (p38/MAPK, extracellular-regulated kinase/MAPK and c-Jun N-terminal kinase/MAPK), nuclear factor-kappaB activity and lipoprotein scavenger receptors (CD36, low-density lipoprotein receptor-1 and scavenger receptor BI) were also detected. Oxidized HDL enhanced reactive oxygen species production and upregulated expression of proinflammatory factors, including tumour necrosis factor-alpha, regulated upon activation, normal T-cell expressed and secreted (RANTES), monocyte chemoattractant protein-1 and CXC chemokine ligand-1 by rat mesangial cells dose in a dependent fashion. Incubation with oxidized HDL also increased rat mesangial cells apoptosis in a dose-dependent manner. These effects partly depended on scavenger receptors CD36 and low-density lipoprotein receptor-1, but not scavenger receptor BI. In addition, co-culture with oxidized HDL activated P38/MAPK, extracellular-regulated kinase (ERK)/MAPK and nuclear factor-kappaB (NF-kappaB). The results of the present study suggest that oxidized HDL enhanced proinflammatory properties in mesangial cells partly via CD36 and low-density lipoprotein receptor-1. MAPK and nuclear factor-kappaB pathways were involved in the process. The ability of oxidized HDL to negatively influence mesangial cell biology may represent an important mechanism of chronic kidney disease.
    Diabetes/Metabolism Research and Reviews 09/2010; 26(6):455-63. · 2.97 Impact Factor
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    ABSTRACT: Due to chemotherapy resistance in osteosarcoma subgroups, the prognosis of these patients is still poor, and the development of new agents is of utmost importance. The aim of our study was to test the antitumor effects of two novel alpha-aryloxy-alpha-methylhydrocinnamic acid derivatives as peroxisome proliferator-activated receptor (PPAR) gamma agonists, together with rosiglitazone, a well-known thiazolidinedione (TZD) acting on several osteosarcoma cell lines. The MTT assay revealed that cell viability was inhibited in a dose-dependent manner with IC(50) 6.2-15.8 microM for the two novel compounds and rosiglitazone (48.4-83.5 microM). Exposure to DG8 and DH9 at low micromolar concentrations induced a dose-dependent block of DNA synthesis and colony formation. In these antitumor assays, DG8 and DH9 were more effective than rosiglitazone, although the PPARgamma agonistic activity of rosiglitazone is much higher. The SiRNA approach to downregulate specifically PPARgamma in U-2OS cells did not affect the cytotoxic efficiency of either the two novel compounds or rosiglitazone. These observations suggest that non-TZDs with less PPARgamma agonistic activity might show more potent antitumor efficacy independent of PPARgamma in human osteosarcoma cells, which supports the possibility that they could be beneficial in the treatment of osteosarcoma patients.
    Chemotherapy 12/2009; 55(6):468-76. · 2.07 Impact Factor
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    ABSTRACT: Dietary protein restriction is one major therapy in chronic kidney disease (CKD), and ketoacids have been evaluated in CKD patients during restricted-protein diets. The objective of the present study was to compare the efficacy of a low-protein diet supplemented with ketoacids (LPD+KA) and a low-protein diet alone (LPD) in halting the development of renal lesions in CKD. 5/6 Nephrectomy Sprague-Dawley rats were randomly divided into three groups, and fed with either 22 % protein (normal-protein diet; NPD), 6 % protein (LPD) or 5 % protein plus 1 % ketoacids (LPD+KA) for 24 weeks. Sham-operated rats were used as controls. Each 5/6 nephrectomy group included fifteen rats and the control group included twelve rats. Proteinuria, decreased renal function, glomerular sclerosis and tubulointerstitial fibrosis were found in the remnant kidneys of the NPD group. Protein restriction ameliorated these changes, and the effect was more obvious in the LPD+KA group after 5/6 nephrectomy. Lower body weight and serum albumin levels were found in the LPD group, indicating protein malnutrition. Lipid and protein oxidative products were significantly increased in the LPD group compared with the LPD+KA group. These findings indicate that a LPD supplemented with ketoacids is more effective than a LPD alone in protecting the function of remnant kidneys from progressive injury, which may be mediated by ketoacids ameliorating protein malnutrition and oxidative stress injury in remnant kidney tissue.
    The British journal of nutrition 11/2009; 103(4):608-16. · 3.45 Impact Factor
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    ABSTRACT: Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disease that exclusively progresses to renal failure. An important target for the treatment of ADPKD is to reduce cystic cell proliferation. PPARγ agonists such as TZDs are insulin sensitizing agents that have also been reported to decrease tumor growth. Here we tested DH9, a newly synthesized PPARγ agonist on the proliferation of an ADPKD cell line, WT9-12. DH9 showed a potent anti-proliferative activity against ADPKD cells. At high concentration, DH9 also induced apoptotic cell death. The effect of DH9 on cell proliferation was mediated by a PPARγ independent mechanism. Since DH9 decreased the levels of β-catenin in cells via a GSK3β mediated degradation pathway, this acts as a mechanism for growth inhibition by DH9.
    Investigational New Drugs 09/2009; 28(6):783-90. · 3.50 Impact Factor
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    ABSTRACT: (E)-Ethyl 3,5-dimethyl-4-[(indolin-2-one-3-ylidene)methyl]-1H-pyrrole-2-carboxylate (B5) was one of the novel pyrrole-substituted indolinones synthesized in our research with the initial aim of developing selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKIs). However, B5 exhibited weak inhibitory potency against a variety of protein tyrosine kinases including EGFR, but potent kinase inhibition against several members of the cyclin-dependent kinase (CDK) family. The results of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay demonstrated that B5 had approximately 500 times more potent antitumor activity than PD153035, a known standard EGFR-TKI, in a panel of ten epithelial cancer cell lines. B5 did not inhibit the phosphorylation of EGFR induced by EGF in vitro. DNA flow cytometric analysis revealed that B5 induced cell cycle arrest at G2/M phase and western blot analysis indicated that both CDK1 (Cdc2) and cyclin B1 proteins were decreased after B5 treatment. Our findings suggested the potential therapeutic applications of B5 in numerous cancers and a promising new template for further development of antitumor agents.
    Investigational New Drugs 02/2009; 28(1):26-34. · 3.50 Impact Factor