Zhenyu Li

Xuzhou Medical College, Suchow, Jiangsu Sheng, China

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Publications (73)185.47 Total impact

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    ABSTRACT: Immune thrombocytopenia (ITP) is an autoimmune disease, characterized by dysregulation of cellular immunity. Previous studies demonstrated that immune imbalance between Th1 and Th2 was associated with the pathogenesis of ITP. Runt-related transcription factor 3 (RUNX3) is a member of the runt domain-containing family of transcription factors and plays an important role in the regulation of T cell differentiation into Th1 cells. Whether RUNX3 was involved in the pathogenesis of ITP remains unclear. In this study, 47 active ITP patients, 18 ITP with remission and 26 age and gender matched healthy control were included. Peripheral blood mononuclear cells (PBMCs) were isolated from ITP and control for isolation of RNA and plasma which were used to measure mRNA level of RUNX3 and T-box transcription factor (T-bet) by quantitative real-time PCR and interferon γ (IFN-γ) plasma level by ELISA. Meanwhile, protein was also extracted from PBMCs for Western blot analysis of RUNX3 expression. Our results showed a significantly higher expression of RUNX3, T-bet and plasma level of IFN-γ in active ITP patients compared to control. No differences were observed between ITP with remission and control. Furthermore, a positive correlation of RUNX3 with T-bet was found in active ITP patients. In conclusion, aberrant expression of RUNX3 was associated with the pathogenesis of ITP and therapeutically targeting it might be a novel approach in ITP treatment. Copyright © 2015. Published by Elsevier B.V.
    International immunopharmacology 06/2015; DOI:10.1016/j.intimp.2015.06.008 · 2.71 Impact Factor
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    ABSTRACT: Prostate cancer is one of the most common cancer types worldwide. In 2014, there were an estimated 233,000 new cases and 29,480 mortalities in the United States. Androgen deprivation therapy, also called androgen suppression therapy, targets androgen signaling and remains the standard treatment for patients with advanced prostate cancer; however, responses to treatment are not durable and most patients advance to castrate-resistant prostate cancer. Therefore, novel therapeutic strategies to treat prostate cancer are urgently required. Heat shock protein 90 (Hsp90) is a chaperone protein that has been shown to regulate the progression of tumor cells. Numerous Hsp90 inhibitors show anti‑tumor activity and several of them have entered clinical trials. Geldanamycin (GA) was identified as the first Hsp90 inhibitor, but shows hepatotoxicity at its effective concentrations, limiting its clinical use. In previous studies by our group, the GA derivative 17-ABAG was designed and synthesized. The present study showed that 17-ABAG inhibits the proliferation and induces apoptosis of LNCaP, an androgen-dependent prostate cancer cell line, in vitro through a classic apoptotic pathway. 17-ABAG also downregulated the Hsp90 client protein and inhibited androgen receptor nuclear localization in LNCaP cells. In addition, 17-ABAG suppressed the growth of LNCaP xenograft tumors without any obvious side-effects. The present study demonstrated that 17-ABAG is a promising anti‑tumor agent and warrants further validation in prospective studies.
    International Journal of Molecular Medicine 06/2015; DOI:10.3892/ijmm.2015.2239 · 1.88 Impact Factor
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    ABSTRACT: Several sesquiterpene lactones have been extracted and demonstrated to exert various pharmacological functions in a variety of cancers. Here, we investigated anti-tumor effect of alantolactone, an allergenic sesquiterpene lactone, on human multiple myeloma (MM) and showed alantolactone inhibited growth of MM cells, both in the presence or absence of bone marrow (BM)-derived stromal cells (HS-5), and subsequent G1 phase arrest, and apoptosis as demonstrated by increased Annexin-V/7-AAD binding, caspase-3 or caspase-9 activation and down-modulation of activation of extracellular signal-regulated kinases 1/2. In addition, alantolactone reduced the secretion of MM survival and growth-related cytokines, vascular endothelial growth factor, from MM cells or HS-5 cells, and inhibited cytokine-induced osteoclastogenesis. Notably, alantolactone also inhibited cell proliferation in bortezomib-resistant MM cells. Taken together, alantolactone exerted anti-tumor effect on MM by suppressing cell proliferation, triggering apoptosis, partly damaging the BM microenvironment and overcoming proteasome inhibitor resistance, suggesting alantolactone may be a novel therapeutic approach for the treatment of human MM.
    APOPTOSIS 06/2015; DOI:10.1007/s10495-015-1140-2 · 3.61 Impact Factor
  • Molecules 06/2015; 20(6):10065-10081. DOI:10.3390/molecules200610065 · 2.42 Impact Factor
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    ABSTRACT: Constitutive NF-κB activation is required for survival and common feature of activated B cell-like subtype of diffuse large B cell lymphoma (ABC-DLBCL). However, current NF-κB targeting strategies lack cancer cell specificity. Here, we identified a novel inhibitor, piperlongumine, feature direct binding to NF-κB p65 subunit and suppression of p65 nuclear import. This was accompanied by NF-κB reporter activity suppression and NF-κB target gene downregulation. Moreover, mutation of Cys(38) to Ser in p65 abolished this effect of piperlongumine on inhibition of p65 nuclear import. Furthermore, we show that piperlongumine selectively inhibited proliferation and induced apoptosis of ABC-DLBCL cells. Most notably, it has been reported that piperlongumine did not affect normal cells even at high doses and was nontoxic to animals. Hence, our current study provides new insight into piperlongumine's mechanism of action and novel approach to ABC-DLBCL target therapy. Copyright © 2015 Elsevier Inc. All rights reserved.
    Biochemical and Biophysical Research Communications 05/2015; 462(4). DOI:10.1016/j.bbrc.2015.04.136 · 2.28 Impact Factor
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    ABSTRACT: The objective of the study is to fabricate multifunctional mesoporous silica nanoparticles for achieving co-delivery of conventional antitumor drug paclitaxel (PTX) and the multidrug resistance reversal agent tetrandrine (TET) expecting to overcome multidrug resistance of MCF-7/ADR cells. The nanoparticles were facile to prepare by self-assemble in situ drug loading approach. Namely, PTX and TET were solubilized in the cetyltrimethylammonium bromide (CTAB) micelles and simultaneously silica resources hydrolyze and condense to form nanoparticles. The obtained nanoparticles, denoted as PTX/TET-CTAB@MSN, exhibited pH-responsive release property with more easily released in the weak acidic environment. Studies on cellular uptake of nanoparticles demonstrated TET could markedly increase intracellular accumulation of nanoparticles. Furthermore, the PTX/TET-CTAB@MSN suppressed tumor cells growth more efficiently than only delivery of PTX (PTX-CTAB@MSN) or the free PTX. Moreover, the nanoparticle loading drugs with a PTX/TET molar ratio of 4.4:1 completely reversed the resistance of MCF-7/ADR cells to PTX and the resistance reversion index was 72.3. Mechanism research showed that both TET and CTAB could arrest MCF-7/ADR cells at G1 phase; and besides PTX arrested cells at G2 phase. This nanocarrier might have important potential in clinical implications for co-delivery of multiple drugs to overcome MDR. Copyright © 2015. Published by Elsevier B.V.
    International Journal of Pharmaceutics 05/2015; 489(1-2). DOI:10.1016/j.ijpharm.2015.05.010 · 3.79 Impact Factor
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    ABSTRACT: Injury to liver sinusoidal endothelial cells (LSECs) is thought to be the initial factor for Hepatic veno-occlusive disease, a severe complication after hematopoietic stem cell transplantation (HSCT). Endothelial progenitor cells (EPCs) have the capacity to differentiate into endothelial cells and play a critical role in vasculogenesis, tissue regeneration and repair. Whether EPCs infusion ameliorates LSECs injury remains unclear. The aim of this study was to evaluate the effects of EPCs on liver injury in mice after HSCT. Mice received HSCT without or with EPCs infusion (HSCT+EPCs). Untreated mice were used as control. Liver and whole blood were collected post HSCT and used for the analysis of pathology of liver sinusoidal endothelial cells (LSECs) and hepatocytes, liver ultrastructure, function, level of IL-6, TNF-α and platelet activation. Severe LSECs injury, hepatocyte damage, abnormal liver function was observed in HSCT group. In addition, increased P-selectin expression and secretion of IL-6, TNF-α was also found. However, all the above changes were alleviated in HSCT+EPCs at all the time points and normalized at the endpoint. Meanwhile, EPCs-induced repair of LSECs and hepatocytes was totally inhibited by the addition of anti-VE-cadherin antibody. EPCs infusion ameliorated the damage to LSECs and hepatocytes as well as reduced secretion of IL-6, TNF-α and inhibited platelet activation after HSCT, leading to improved liver function, suggesting EPCs might be a new therapeutic strategy in the prophylaxis of liver injury after HSCT. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Liver international: official journal of the International Association for the Study of the Liver 04/2015; DOI:10.1111/liv.12849 · 4.41 Impact Factor
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    ABSTRACT: Heat shock protein 90 (Hsp90) is a molecular chaperone involved in the stability of many client proteins, including androgen receptor (AR) and survivin, making Hsp90 an attractive molecular therapeutic target for prostate cancer. Several Hsp90 inhibitors have shown antitumor activity in various preclinical models and in clinical trials. Geldanamycin is a well-known inhibitor of Hsp90, but its associated liver toxicity limited its clinical development. Here, we report a highly effective and low-hepatotoxic geldanamycin derivative that exhibits antitumor activity against human prostate cancer cells. Treatment of cells with 17-DMCHAG (17-(6-(3,4-dimethoxycinnamamido)hexylamino)-17-demethoxy-geldanamycin) dose-dependently suppressed the proliferation, reduced colony formation and induced apoptosis of human prostate cancer cell lines. 17-DMCHAG exhibits anti-invasive and anti-migratory activities in prostate cancer cells through down-regulating of transcription factors Zeb1, Snail1, Slug, and mesenchymal marker Vimentin, while up-regulating the epithelial marker of E-cadherin. Furthermore, 17-DMCHAG treatment damaged the Hsp90/AR and Hsp90/survivin complexes and induced the proteasome-dependent degradation of AR and survivin, then inhibited the activity of these two proteins. In vivo, we observed that 17-DMCHAG showed strong antitumor effects in LNCaP and DU-145 cell-xenografted nude mice. Thus, 17-DMCHAG is a potential treatment for prostate cancer. Copyright © 2015. Published by Elsevier Ireland Ltd.
    Cancer letters 03/2015; 362(1). DOI:10.1016/j.canlet.2015.03.025 · 5.02 Impact Factor
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    ABSTRACT: To observe the efficacy of high-dose dexamethasone in combination with low-dose rituximab as a second-line treatment for patients with immune thrombocytopenia (ITP). 65 patients with ITP, previously by conventional dose of glucocorticoids, received high-dose dexamethasone in combination with low-dose rituximab (dexamethasone 40 mg/d for 4 days, rituximab 100 mg, d 7, 14, 21, 28 intravenous infusion). Treatment response, regulatory T cells (Treg), cytokines levels and treatment-related adverse effects were observed. Total response rate 1 month after treatment was achieved in 81.5% (53/65) of patients, and complete response at 3,6 and 12 months was 72.3% (47/65), 66.2%(43/65), 63.1%(41/65). The higher efficiency and complete response rate was achieved in preexisting glucocorticoid-dependent patients. For patients with complete response, Treg cells continued to show a high level state [(3.01±0.95)% vs (1.69±0.35)%, P=0.032], cytokines of BAFF [(648.03±79.63) ng/L vs (972.35±93.64) ng/L, P=0.001], IL-2 [(2.84±0.32) ng/L vs (4.18±0.46) ng/L, P=0.012], sCD40L[(4.55±0.66) ng/L vs (7.73±1.04) ng/L, P=0.006] significantly lower than that before treatment. The level of IL-10 was increased, but without significance compared with that before treatment (P=0.136). All patients completed the protocol with no serious adverse reactions. The data show high-dose dexamethasone in combination with low-dose rituximab still has a satisfactory outcomes for patients previously with conventional dose of glucocorticoid.
    Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi 03/2015; 36(3):206-9. DOI:10.3760/cma.j.issn.0253-2727.2015.03.007
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    ABSTRACT: Sweetness is a traditional sensory indicator used to evaluate the quality of the popular Chinese herb Radix Astragali (RA). RA roots with strong sweetness are considered to be of good quality. However, neither a thorough analysis of the component(s) contributing to RA sweetness, nor a scientific investigation of the reliability of this indicator has been conducted to date. In this study, seven kinds of sweetness components were identified in RA and a quality evaluation method based on these components was established and used to characterize the quality of 48 RA samples. The sweetness evaluation method of RA was first built based on the sweetness components, and a comprehensive evaluation index commonly used in quality control of RA was also derived, which was based on the contents of four indicators (astragaloside IV, calycosin glucoside, polysaccharides and extracts). After evaluating the correlation of these indexes the results showed that the level of sweetness exhibited a strong positive correlation with the proposed comprehensive index. Our results indicate that sweetness is one of the most important quality attributes of RA and thus provide a scientific basis for the utility of the sweetness indicator in quality assessment of this Chinese herb.
    Molecules 02/2015; 20(2):3129-45. DOI:10.3390/molecules20023129 · 2.42 Impact Factor
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    ABSTRACT: A series of 17-phenylpropylamine/phenoxyethylamine-substituted derivatives of geldanamycin (GA) was synthesized and evaluated for the anti-proliferation activity on human cancer cell line MDA-MB-231. All the derivatives exhibited potent cytotoxicity with IC50 values range from 0.35 to 1.03 μM. Among them, 17-(2-phenoxyethylamino)-17-demethoxygeldanamycin (3) was identified as the most potent compound. Hepatotoxicity test in mice demonstrated that the levels of both aspartate aminotransferase (AST) and alanine aminotransferase (ALT) of 3-treated group were lower than that of GA-treated group, indicating that compound 3 was a promising antitumor candidate. Additionally, the Hsp90 inhibitory activity of compound 3 was more active than 17-AAG. Docking and molecular dynamics (MD) refinements of this new series of GA derivatives were also investigated, suggesting a theoretical model between 17-phenylpropylamine/phenoxyethylamines and Hsp90.
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    ABSTRACT: The effect of infusion of lentiviral vector‑mediated, genetically engineered dendritic cells (DCs) following allogeneic bone marrow transplantation (allo‑BMT) on graft‑versus‑host disease (GVHD) and graft‑versus‑leukemia (GVL) was investigated in a mouse model. Lentivirus‑mediated expression of soluble tumor necrosis factor receptor 1 (sTNFR1) converted immature DCs (imDCs) from BABL/c mice into engineered DCs in vitro. An EL4 leukemia allo‑BMT model of BABL/c to C57BL/6 mice was established. Engineered DCs with donor bone marrow cells and splenocytes were subsequently transplanted into myeloablatively irradiated recipients. The average survival duration in the sTNFR1‑ and pXZ9‑imDC groups was significantly prolonged compared with that of the allo‑BMT group (P<0.05). Mild histological changes in GVHD or leukemia were observed in the recipients in the sTNFR1‑imDC group and clinical GVHD scores in this group were significantly decreased compared with those of the transplantation and pXZ9‑imDC groups. Serum interferon‑γ levels were decreased in the pXZ9‑imDC and sTNFR1‑imDC groups compared with those in the allo‑BMT group (P<0.05), with the reduction being more significant in the sTNFR1‑imDC group (P<0.05). Serum interleukin‑4 expression levels were decreased in the allo‑BMT group, but gradually increased in the pXZ9‑imDC and sTNFR1‑imDC groups (P<0.05). Co‑injection of donor genetically‑engineered imDCs was able to efficiently protect recipient mice from lethal GVHD while preserving GVL effects during allo‑BMT.
    Molecular Medicine Reports 12/2014; DOI:10.3892/mmr.2014.3123 · 1.48 Impact Factor
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    ABSTRACT: Mesenchymal stem cells (MSCs) are a promising candidate for cellular therapies. Co-transplantation of MSCs and hematopoietic stem cells (HSCs) promotes successful engraftment and improves hematopoietic recovery. In this study, the effects of co-transplantation of HSCs and mouse bone marrow (BM)-derived MSCs overexpressing CXCR4 (CXCR4-MSC) on CXCR4-MSC homing capacity and the reconstitution potential in lethally irradiated mice were evaluated. Recovery of donor-derived peripheral blood leukocytes and platelets was accelerated when CXCR4-MSCs were co-transplanted with BM cells. The frequency of c-kit(+)Sca(+)Lin(-) HSCs was higher in recipient BM following co-transplantation of CXCR4-MSCs compared with the EGFP-MSC control and the BMT only groups. Surprisingly, the rate of early engraftment of donor-derived BM cells in recipients co-transplanted with CXCR4-MSCs was slightly lower than in the absence of MSCs on day 7. Moreover, co-transplantation of CXCR4-MSCs regulated the balance of T helper cells subsets. Hematopoietic tissue reconstitution was evaluated by histopathological analysis of BM and spleen. Co-transplantation of CXCR4-MSCs was shown to promote the recovery of hematopoietic organs. These findings indicate that co-transplantation of CXCR4-MSCs promotes the early phase of hematopoietic recovery and sustained hematopoiesis.
    Cell Biochemistry and Biophysics 11/2014; 71(3). DOI:10.1007/s12013-014-0381-y · 2.38 Impact Factor
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    ABSTRACT: To investigate the effect of the lentiviral vector mediated CXCR4 overexpressed mesenchymal stem cell (MSCs) on graft-versus-host disease (GVHD).
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    ABSTRACT: Heat shock protein 90 (Hsp90) is an attractive target for the development of antitumor agents. Geldanamycin (GA), the first Hsp90 inhibitor, has potent antitumor activity, but showed significant hepatotoxicity. To get rid of the hepatotoxicity of GA, in this study we incorporated aroyl groups via three types of linkers (4-aminomethylpiperidine, 1,4-butanediamine, and 1,6-hexanediamine) to the 17-position of GA and synthesized fifty-three 17-diamine-linked 17-aroylamido-17-demethoxygeldanamycins. All the derivatives were evaluated by MTT assay for their inhibitory activities against human breast cancer cell line MDA-MB-231. Among these compounds, 17-(6-(3,4,5-trimethoxycinnamamido)hexylamino)-17-demethoxygeldanamycin (7h29) showed the most potent cytotoxicity against MDA-MB-231 (IC50 = 0.19 ± 0.02 μM) with the lowest hepatotoxicity (AST = 181.0 ± 23.6 U/L, ALT = 40.4 ± 11.8 U/L). Compared to tanespimycin (17-AAG), 7h29 exhibited lower hepatotoxicity in mice, higher Hsp90 inhibitory activity in vitro and antitumor activity in human breast carcinoma (MDA-MB-231) xenograft nude mice.
    European Journal of Medicinal Chemistry 09/2014; 87:346–363. DOI:10.1016/j.ejmech.2014.09.078 · 3.43 Impact Factor
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    ABSTRACT: DNA topoisomerase II (Topo II) is an essential nuclear enzyme and a validated target for anticancer agent screening. CS1, a novel 2-phenylnaphthalene, had potent cytotoxicity against nine tested tumor cell lines and showed 6–10-fold less toxicity against normal cell lines compared with etoposide. In addition, CS1 showed potential anti-multidrug resistance capabilities. kDNA decatenation, DNA relaxation and cleavage complex assay indicate that CS1 works as an nonintercalating topoisomerase IIα (Topo IIα) inhibitor by stabilizing the DNA-Topo IIα cleavage complex. CS1 also induced DNA breaks in cells evidenced by comet tails in MDA-MB-231 cells and accumulation of γH2AX foci. The ability of CS1 in inducing DNA breaks mediated by Topo II resulted in G2/M phase arrest and apoptosis. Moreover, CS1 exhibited dramatic in vivo antitumor activity and lower toxicity compared with etoposide. This work supports the development of CS1 as a promising candidate for treatment of cancer by targeting Topo IIα.
    Biochemical and Biophysical Research Communications 09/2014; 453(3). DOI:10.1016/j.bbrc.2014.09.042 · 2.28 Impact Factor
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    ABSTRACT: Forty eight 2-phenylnaphthalenoids were designed and successfully synthesized. Their in vitro cytotoxicities against the proliferations of MDA-MB-231, A549 and HeLa cell lines and inhibitory activities on DNA topoisomerase were evaluated. The quantitative structure-activity relationship (QSAR) studies were established on the basis of cytotoxicity data from MDA-MB-231 cell line. Among these compounds, compound 5 showed potent antiproliferative activity (IC50 = 1 μM) against MDA-MB-231 cells and inhibitory activity on topoisomeraseIIα. Further, in vivo antitumor study with xenograft nude mice indicated that compound 5 inhibited the growth of MDA-MB-231 cells and showed lower toxicity than etoposide (VP16). This work indicates that 2-phenylnaphthalenoids represent a novel type of TopoIIα-inhibitory scaffold for developing new antitumor chemotherapeutic agents.
    European Journal of Medicinal Chemistry 09/2014; 86C:782-796. DOI:10.1016/j.ejmech.2014.08.073 · 3.43 Impact Factor
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    ABSTRACT: Astragali Radix (Huangqi), a well-known traditional Chinese medicinal plant, has been used for centuries as a reinforcing vital energy herb in China. In this study, the antifatigue effect of Astragali Radix was investigated by 1H NMR based metabolomic approach coupled with multivariate statistical analysis. The results indicated that oral administration of Astragali Radix at a dose of 3g/kg body weight could significantly prolong the exhaustive swimming time of rats, and alter the serum and urine metabolome. The rats treated by Astragali Radix extracts showed higher levels of glucose, creatine, glycine, citrate, guanidinoacetate, allantoin, dimethylglycine, dimethylamine (DMA), creatinine, betaine and malate and lower levels of lactate, choline species, O-acetylated glycoproteins (OAG), glycerol, β-OH-butyrate, α-ketoglutarate, trimethylamine (TMA) and hippurate. And these metabolic changes indicated that Astragali Radix facilitated recovery from fatigue by regulating the glycometabolism, lipid metabolism and energy metabolism. Chemical analysis showed that various components were present in the Astragali Radix extracts, the bioactive compounds responsible for the antifatigue activity should be further investigated.
    Molecular BioSystems 09/2014; 10(11). DOI:10.1039/C4MB00370E · 3.18 Impact Factor
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    ABSTRACT: To explore the expression and significance of miRNAs and Th17 related cytokines in patients with multiple myeloma (MM). A total of 27 MM patients and 8 health controls were enrolled in this study. The expression of miR-15a/16,miR-34a,miR-194-2-192 cluster and miR-181a/b in bone marrow were detected by real-time quantitative PCR (qRT-PCR). Enzyme-linked immunosorbent assay (ELISA) was used to determine the levels of Th17 related cytokines interleukin-17 (IL-17), IL-21, IL-22, IL-23 and IL-27 in peripheral blood plasma. The role of miRNAs and Th17 related cytokines was analyzed in the development of MM. The expression of miR-15a/16,miR-34a,miR-194-2-192 cluster in MM patients were significantly lower than those of the health controls, while miR-181a/b were exactly the reverse (P<0.05). The levels of IL-17, IL-21 and IL-27 were up-regulated in MM patients compared to health controls while IL-22 was down-regulated (P<0.05). There was no significant difference of IL-23 between the two groups. The levels of miRNAs and Th17 related cytokines had associated with ISS but not with some clinical parameters (such as gender, age, disease classification). Higher expression of IL-17, IL-21, IL-23, IL-27, miR-181a/b and lower expression of miR-15a/16,miR-34a,miR-194 and IL-22 were observed in the end stage than the early stage of MM patients (P<0.05). There was a significant correlation between miRNAs and Th17 related cytokines. Up-regulated IL-17, IL-21 and IL-27 may potentially down-regulate the expression of several miRNAs in MM patients. Establishment of the relationship may be useful for understanding the pathogenesis of MM and for clinical diagnosis of the disease.
    Leukemia Research 09/2014; 36(2). DOI:10.1016/j.leukres.2014.07.005 · 2.69 Impact Factor
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    ABSTRACT: BackgroundThe dried root of Polygala tenuifolia, named Radix Polygalae, is a well-known traditional Chinese medicine. Triterpenoid saponins are some of the most important components of Radix Polygalae extracts and are widely studied because of their valuable pharmacological properties. However, the relationship between gene expression and triterpenoid saponin biosynthesis in P. tenuifolia is unclear.Methodology/FindingsIn this study, ultra-performance liquid chromatography (UPLC) coupled with quadrupole time-of-flight mass spectrometry (Q-TOF MS)-based metabolomic analysis was performed to identify and quantify the different chemical constituents of the roots, stems, leaves, and seeds of P. tenuifolia. A total of 22 marker compounds (VIP>1) were explored, and significant differences in all 7 triterpenoid saponins among the different tissues were found. We also observed an efficient reference gene GAPDH for different tissues in this plant and determined the expression level of some genes in the triterpenoid saponin biosynthetic pathway. Results showed that MVA pathway has more important functions in the triterpenoid saponin biosynthesis of P. tenuifolia. The expression levels of squalene synthase (SQS), squalene monooxygenase (SQE), and beta-amyrin synthase (β-AS) were highly correlated with the peak area intensity of triterpenoid saponins compared with data from UPLC/Q-TOF MS-based metabolomic analysis.Conclusions/SignificanceThis finding suggested that a combination of UPLC/Q-TOF MS-based metabolomics and gene expression analysis can effectively elucidate the mechanism of triterpenoid saponin biosynthesis and can provide useful information on gene discovery. These findings can serve as a reference for using the overexpression of genes encoding for SQS, SQE, and/or β-AS to increase the triterpenoid saponin production of P. tenuifolia.
    PLoS ONE 08/2014; 9(8):e105765. DOI:10.1371/journal.pone.0105765 · 3.53 Impact Factor

Publication Stats

417 Citations
185.47 Total Impact Points

Institutions

  • 2009–2015
    • Xuzhou Medical College
      • Department of Hematology
      Suchow, Jiangsu Sheng, China
    • Shandong University
      • • School of Pharmaceutical Sciences
      • • Institute for Medicine Chemistry
      Chi-nan-shih, Shandong Sheng, China
  • 2010–2014
    • Shanxi University
      • School of Chemistry and Chemical Engineering
      Yangkü, Shanxi Sheng, China