Publications by authors named "Linlin Shao"

28 Publications

  • Page 1 of 1

Proteomic analysis and microRNA expression profiling of plasma-derived exosomes in primary immune thrombocytopenia.

Br J Haematol 2021 Sep 1;194(6):1045-1052. Epub 2021 Aug 1.

Department of Hematology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.

Exosomes are released into extracellular fluids and have emerged as vital biological mediators in autoimmune diseases. Plasma-derived exosomes have been reported to take part in the pathogenesis of primary immune thrombocytopenia (ITP), but the protein and miRNA cargoes have not been entirely elucidated. Via proteomic analysis and RNA sequencing on plasma-derived exosomes from ITP patients and healthy controls, we found one upregulated exosomal protein (apolipoprotein E, ApoE), six downregulated exosomal miRNAs (miR-584-5p, miR-4433a-5p, miR-4433b-3p, miR-6842-3p, miR-130b-5p and miR-222-3p), and 10 upregulated exosomal miRNAs (miR-29a-3p, miR-142-5p, miR-16-2-3p, miR-29b-3p, miR-501-3p, miR-144-5p, miR-192-5p, miR-182-5p, miR-363-3p and miR-96-5p) in ITP patients. The elevated exosomal protein candidate ApoE in the ITP cohort was further validated using western blot. Via quantitative real-time polymerase chain reaction assays, three differentially expressed miRNAs (miR-584-5p, miR-142-5p and miR-29b-3p) were identified. This study provides direct evidence for a restricted signature of exosomal protein and miRNAs which distinguishes ITP from healthy controls. The results require further validation in larger independent ITP cohorts, which will provide insights into the potential pathophysiological significance of circulating exosomes in ITP.
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http://dx.doi.org/10.1111/bjh.17720DOI Listing
September 2021

Predictive Value of High ICAM-1 Level for Poor Treatment Response to Low-Dose Decitabine in Adult Corticosteroid Resistant ITP Patients.

Front Immunol 2021 13;12:689663. Epub 2021 Jul 13.

Department of Hematology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.

Primary immune thrombocytopenia (ITP) is an autoimmune hemorrhagic disease. Endothelial cell activation/injury has been found in some autoimmune diseases including SLE, systemic sclerosis, and rheumatoid arthritis, but its role in ITP pathogenesis remains unclear. This study attempted to elucidate the correlation between endothelial dysfunction and disease severity of ITP and find related markers to predict response to low-dose decitabine treatment. Compared with healthy volunteers, higher plasma levels of soluble intercellular adhesion molecule-1 (ICAM-1), vascular endothelial growth factor (VEGF), and Angiopoietin-2 were found in adult corticosteroid resistant ITP patients. Notably, ICAM-1 levels were negatively correlated with the platelet count, and positively associated with the bleeding score. Recently, we have reported the efficacy and safety of low-dose decitabine in adult patients with ITP who failed for the first line therapies. Here, we evaluated the correlation of plasma ICAM-1 level with the efficacy of low-dose decitabine therapy for corticosteroid resistant ITP. A total of 29 adult corticosteroid resistant ITP patients who received consecutive treatments of low-dose decitabine were enrolled in this study. Fourteen patients showed response (nine showed complete response and five showed partial response). The levels of ICAM-1 before and after treatment were significantly higher in the non-responsive ITP patients than in the responsive patients. As shown in the multivariable logistic regression model, the odds of developing no-response to low-dose decitabine increased by 36.8% for per 5 ng/ml increase in plasma ICAM-1 level [odds ratio (OR) 1.368, 95% confidence interval (CI): 1.060 to 1.764]. In summary, this was the first study to elucidate the relationship between endothelial dysfunction and corticosteroid resistant ITP and identify the potential predictive value of ICAM-1 level for response to low-dose decitabine.
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http://dx.doi.org/10.3389/fimmu.2021.689663DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8313967PMC
July 2021

Dexamethasone plus oseltamivir versus dexamethasone in treatment-naive primary immune thrombocytopenia: a multicentre, randomised, open-label, phase 2 trial.

Lancet Haematol 2021 Apr;8(4):e289-e298

Department of Haematology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.

Background: Primary immune thrombocytopenia is an autoimmune bleeding disorder. Preclinical reports suggest that the sialidase inhibitor oseltamivir induces a platelet response in the treatment of immune thrombocytopenia. This study investigated the activity and safety of dexamethasone plus oseltamivir versus dexamethasone alone as initial treatment in adult patients with primary immune thrombocytopenia.

Methods: This multicentre, randomised, open-label, parallel group, phase 2 trial was done in five tertiary medical hospitals in China. Eligible patients were aged 18 years or older with newly diagnosed, treatment-naive primary immune thrombocytopenia. Participants were randomly assigned (1:1), using block randomisation, to receive either dexamethasone (orally at 40 mg per day for 4 days) plus oseltamivir (orally at 75 mg twice a day for 10 days) or dexamethasone monotherapy (orally at 40 mg a day for 4 days). Patients who did not respond to treatment (platelet counts remained <30 × 10 cells per L or showed bleeding symptoms by day 10) were given an additional cycle of dexamethasone for 4 days in each group. Patients in the dexamethasone plus oseltamivir group who relapsed (platelet counts reduced again to <30 × 10 cells per L) after an initial response were allowed a supplemental course of oseltamivir (75 mg twice a day for 10 days). The coprimary endpoints were 14-day initial overall response and 6-month overall response. Complete response was defined as a platelet count at or above 100 × 10 cells per L and an absence of bleeding. Partial response was defined as a platelet count at or above 30 × 10 cells per L but less than 100 × 10 cells per L and at least a doubling of the baseline platelet count and an absence of bleeding. A response lasting for at least 6 months without any additional primary immune thrombocytopenia-specific intervention was defined as sustained response. All patients who were randomly assigned and received the allocated intervention were included in the modified intention-to-treat population analysis. This study has been completed and is registered with ClinicalTrials.gov, number NCT01965626.

Findings: From Feb 1, 2016, to May 1, 2019, 120 patients were screened for eligibility, of whom 24 were ineligible and excluded, 96 were enrolled and randomly assigned to receive dexamethasone plus oseltamivir (n=47) or dexamethasone (n=49), and 90 were included in the modified intention-to-treat analysis. Six patients did not receive the allocated intervention. Patients in the dexamethasone plus oseltamivir group had a significantly higher initial response rate (37 [86%] of 43 patients) than did those in the dexamethasone group (31 [66%] of 47 patients; odds ratio [OR] 3·18; 95 CI% 1·13-9·23; p=0·030) at day 14. The 6-month sustained response rate in the dexamethasone plus oseltamivir group was also significantly higher than that in the dexamethasone group (23 [53%] vs 14 [30%]; OR 2·17; 95 CI% 1·16-6·13; p=0·032). During the median follow-up of 8 months (IQR 5-14), two of 90 patients discontinued treatment due to serious adverse events (grade 3); one (2%) patient with general oedema in the dexamethasone plus oseltamivir group and one (2%) patient with fever in the dexamethasone group. The most frequently observed adverse events of any grade were fatigue (five [12%] of 43 in the dexamethasone plus oseltamivir group vs eight [17%] of 47 in the dexamethasone group), gastrointestinal reactions (eight [19%] vs three [6%]), insomnia (seven [16%] vs four [9%]), and anxiety (five [12%] vs three [6%]). There were no grade 4 or 5 adverse events and no treatment-related deaths.

Interpretation: Dexamethasone plus oseltamivir offers a readily available combination therapy in the management of newly diagnosed primary immune thrombocytopenia. The preliminary activity of this combination warrants further investigation. Multiple cycles of oseltamivir, as a modification of current first-line treatment, might be more effective in maintaining the platelet response.

Funding: National Natural Science Foundation of China.
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http://dx.doi.org/10.1016/S2352-3026(21)00030-2DOI Listing
April 2021

Hesperetin attenuates silica-induced lung injury by reducing oxidative damage and inflammatory response.

Exp Ther Med 2021 Apr 28;21(4):297. Epub 2021 Jan 28.

Shandong Academy of Occupational Health and Occupational Medicine, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong 250062, P.R. China.

Oxidative stress and the inflammatory response are two important mechanisms of silica-induced lung injury. Hesperetin (HSP) is a natural flavonoid compound that is found in citrus fruits and has been indicated to exhibit strong antioxidant and anti-inflammatory properties. The current study evaluated the protective effect of HSP on lung injury in rats exposed to silica. The results indicated that the degree of alveolitis and pulmonary fibrosis in the HSP-treated group was significantly decreased compared with the silica model group. The content of hydroxyproline (HYP) was also revealed to decrease overall in the HSP treated group compared with the silica model group, indicating that the degree of pulmonary fibrosis was decreased compared with the silica model group. The present study also demonstrated that HSP reduced oxidation levels of malondialdehyde (MDA) and increased the activities of antioxidant enzymes superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-PX). Total antioxidant capacity (T-AOC) was also increased following HSP treatment, indicating that HSP can alleviate oxidative stress in the lung tissue of silica-exposed rats. In addition, HSP was revealed to inhibit the synthesis and secretion of fibrogenic factor TGF-β1, reduce the production of pro-inflammatory cytokines IL-1β, IL-4, TNF-α and increase the levels of anti-inflammatory factors IFN-γ and IL-10. The current study demonstrated that HSP can effectively attenuate silica-induced lung injury by reducing oxidative damage and the inflammatory response.
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http://dx.doi.org/10.3892/etm.2021.9728DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7885076PMC
April 2021

Identification of a pathogenic variant in a Chinese family with congenital macrothrombocytopenia through whole genome sequencing.

Platelets 2021 Jan 5:1-5. Epub 2021 Jan 5.

Department of Hematology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.

Congenital macrothrombocytopenia is a genetically heterogeneous group of rare disorders. We herein report a large Chinese family presented with phenotypic variability involving thrombocytopenia and/or giant platelets. Whole genome sequencing (WGS) of the proband and one of his affected brothers identified a potentially pathogenic c.952 C > T heterozygous variant in the gene. This p.R318W β1-tubulin variant was also identified in three additional siblings and five members of the next generation. These findings were consistent with an autosomal dominant inheritance with incomplete penetrance. Moreover, impaired platelet agglutination in response to ristocetin was detected in the patient's brother. Half of the family members harboring the p.R318W mutation displayed significantly decreased external release of -selectin by stimulated platelets. The p.R318W β1-tubulin mutation was identified for the first time in a Chinese family with congenital macrothrombocytopenia using WGS as an unbiased sequencing approach. Affected individuals within the family demonstrated impaired platelet aggregation and/or release functions.
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http://dx.doi.org/10.1080/09537104.2020.1869714DOI Listing
January 2021

Emodin attenuates silica-induced lung injury by inhibition of inflammation, apoptosis and epithelial-mesenchymal transition.

Int Immunopharmacol 2021 Feb 23;91:107277. Epub 2020 Dec 23.

Shandong Academy of Occupational Health and Occupational Medicine, Shandong First Medical University & Shandong Academy of Medical Sciences, Ji'nan, Shandong, China; The University of Queensland, Queensland Alliance for Environmental Health Sciences (QAEHS), Brisbane, Queensland, Australia. Electronic address:

Silicosis is a fatal pulmonary disease caused by the inhalation of silica dust, and characterized by inflammation and fibrosis of the lung, with no effective treatment to date. Here we investigate the effect of emodin, an anthraquinone derivative isolated from rhubarb using a mouse silicosis model and in vitro cultured human macrophages and alveolar epithelial cells. Results from histological examination indicated that emodin reduced the degree of alveolitis and fibrosis in the lungs of mice exposed to silica particles. We also demonstrated that emodin effectively inhibited the phosphorylation of Smad3 and NF-κB and reduced the levels of inflammatory factors in the lung tissue of mice treated with silica particles. In addition, we found that emodin inhibited apoptosis and demonstrated an anti-fibrotic effect by down-regulating the pro-apoptotic protein Bax and up-regulating the anti-apoptotic protein Bcl-2. Furthermore, emodin increased E-cadherin levels, reduced the expression of Vimentin, α-SMA and Col-I, as well as pro-inflammatory factors TGF-β1, TNF-α and IL-1β in vivo and in vitro. These results suggested that emodin can regulate epithelial-mesenchymal transition (EMT) through the inhibition of the TGF-β1/Smad3 signaling pathway and the NF-κB signaling pathway to prevent alveolar inflammation and apoptotic process. Overall, this study showed that emodin can alleviate pulmonary fibrosis in silicosis through regulating the inflammatory response and fibrotic process at multiple levels.
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http://dx.doi.org/10.1016/j.intimp.2020.107277DOI Listing
February 2021

Indole/isatin-containing hybrids as potential antibacterial agents.

Arch Pharm (Weinheim) 2020 Oct 15;353(10):e2000143. Epub 2020 Jul 15.

School of Life Sciences, Dezhou University, Dezhou, Shandong, China.

The emergence and worldwide spread of drug-resistant bacteria have already posed a serious threat to human life, creating the urgent need to develop potent and novel antibacterial drug candidates with high efficacy. Indole and isatin (indole-2,3-dione) present a wide structural and mechanistic diversity, so their derivatives possess various pharmacological properties and occupy a salient place in the development of new drugs. Indole/isatin-containing hybrids, which demonstrate a promising activity against a panel of clinically important Gram-positive and Gram-negative bacteria, are privileged scaffolds for the discovery of novel antibacterial candidates. This review, covering articles published between January 2015 and May 2020, focuses on the development and structure-activity relationship (SAR) of indole/isatin-containing hybrids with potential application for fighting bacterial infections, to facilitate further rational design of novel drug candidates.
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http://dx.doi.org/10.1002/ardp.202000143DOI Listing
October 2020

miR193b Promotes Apoptosis of Gastric Cancer Cells via Directly Mediating the Akt Pathway.

Biomed Res Int 2020 25;2020:2863236. Epub 2020 May 25.

Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing 100050, China.

Gastric cancer (GC) is one of the most common and fatal malignancies worldwide. MicroRNAs (miRNAs) play a critical role in tumor initiation, proliferation, and metastasis of gastric cancer. miR193b has been identified as a tumor suppressor in a variety of tumor types; however, its role in gastric cancer is yet to be determined. Here, we found a significant downregulation of miR193b expression in both human gastric cancer tissues ( < 0.05) and human gastric cancer cell lines ( < 0.01). Furthermore, the expression level of miR193b correlated with the tumor type, tumor size, and clinical stage ( < 0.05). In vitro, miR193b overexpression inhibited cell survival and induced apoptosis in GC cell lines, indicating that miR193b plays a role in the development of gastric cancer. KRAS was verified as the target of miR193b, and KRAS overexpression attenuated miR193b-induced apoptosis ( < 0.05). Moreover, we found that the Akt pathway negatively regulated miR193b, also affecting apoptosis. Further analyses indicated that PIK3CA mutation and KRAS amplification are two mutually exclusive pathways ( < 0.01), and we hypothesize that both two pathways could result in the carcinogenic overactivation of KRAS. Thus, our results suggest that the Akt-miR193b-KRAS axis may act as a mechanism affecting apoptosis in gastric cancer cells.
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http://dx.doi.org/10.1155/2020/2863236DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7273449PMC
March 2021

Dexamethasone suppresses the Th17/1 cell polarization in the CD4 T cells from patients with primary immune thrombocytopenia.

Thromb Res 2020 06 5;190:26-34. Epub 2020 Apr 5.

Department of Hematology, Qilu Hospital of Shandong University, Jinan, China; Shandong Provincial Key Laboratory of Immunohematology, Qilu Hospital of Shandong University, Jinan, China. Electronic address:

Introduction: Primary immune thrombocytopenia (ITP) is an acquired autoimmune disease with increased Th17 cells in peripheral blood. Th17/1 cells, which were recently characterized as a new differentiated Th17 lineage secreting IL-17 and IFN-γ, play an important role in the pathogenesis of multiple autoimmune diseases. In this study, we investigated whether Th17/1 cells are involved in the pathogenesis of ITP.

Materials And Methods: Peripheral blood was obtained from 44 ITP patients and 50 healthy controls. The percentages of T cell subsets were evaluated. We also detected molecular signature of Th17/1 cells in CD4 T cells. Besides, CD4 T cells from ITP patients were treated with dexamethasone, the inhibitor of NF-κB, or rapamycin to evaluate the impact and mechanism of dexamethasone treatment on Th17/1 cells.

Results: We found an elevated percentage and an enhanced specific molecular signature of Th17/1 cells in CD4 T cells in ITP patients. The percentage of Th17/1 cells was correlated positively with Th17 cells in ITP patients and healthy controls. The percentage of Th17/1 cells was correlated with corticosteroid resistance. Dexamethasone reversed the molecular signature of Th17/1 cells and decreased the percentage of Th17/1 cells in vitro. Treatment of dexamethasone and the inhibitor of NF-κB suppressed the phosphorylation of STAT3, while dexamethasone treatment also inhibited the phosphorylation of NF-κB p65.

Conclusions: Our data suggested Th17/1 cells may contribute to the pathogenesis of ITP and dexamethasone could inhibit Th17/1 cells through NF-κB/STAT3 pathway. These results may provide a potential therapeutic strategy of correcting the Th17/1 cell deviation in ITP.
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http://dx.doi.org/10.1016/j.thromres.2020.04.004DOI Listing
June 2020

Meningeal lymphatic vessels regulate brain tumor drainage and immunity.

Cell Res 2020 03 24;30(3):229-243. Epub 2020 Feb 24.

Institute of Molecular Medicine, Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Peking University, 100871, Beijing, China.

Recent studies have shown that meningeal lymphatic vessels (MLVs), which are located both dorsally and basally beneath the skull, provide a route for draining macromolecules and trafficking immune cells from the central nervous system (CNS) into cervical lymph nodes (CLNs), and thus represent a potential therapeutic target for treating neurodegenerative and neuroinflammatory diseases. However, the roles of MLVs in brain tumor drainage and immunity remain unexplored. Here we show that dorsal MLVs undergo extensive remodeling in mice with intracranial gliomas or metastatic melanomas. RNA-seq analysis of MLV endothelial cells revealed changes in the gene sets involved in lymphatic remodeling, fluid drainage, as well as inflammatory and immunological responses. Disruption of dorsal MLVs alone impaired intratumor fluid drainage and the dissemination of brain tumor cells to deep CLNs (dCLNs). Notably, the dendritic cell (DC) trafficking from intracranial tumor tissues to dCLNs decreased in mice with defective dorsal MLVs, and increased in mice with enhanced dorsal meningeal lymphangiogenesis. Strikingly, disruption of dorsal MLVs alone, without affecting basal MLVs or nasal LVs, significantly reduced the efficacy of combined anti-PD-1/CTLA-4 checkpoint therapy in striatal tumor models. Furthermore, mice bearing tumors overexpressing VEGF-C displayed a better response to anti-PD-1/CTLA-4 combination therapy, and this was abolished by CCL21/CCR7 blockade, suggesting that VEGF-C potentiates checkpoint therapy via the CCL21/CCR7 pathway. Together, the results of our study not only demonstrate the functional aspects of MLVs as classic lymphatic vasculature, but also highlight that they are essential in generating an efficient immune response against brain tumors.
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http://dx.doi.org/10.1038/s41422-020-0287-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7054407PMC
March 2020

Human leukocyte antigen-G upregulates immunoglobulin-like transcripts and corrects dysfunction of immune cells in immune thrombocytopenia.

Haematologica 2021 03 1;106(3):770-781. Epub 2021 Mar 1.

Department of Hematology, Qilu Hospital, Shandong University, Jinan, China

Human leukocyte antigen-G (HLA-G) is a non-classical major histocompatibility complex class I antigen with potent immune-inhibitory function. HLA-G benefit patients in allotransplantation and autoimmune diseases by interacting with its receptors, immunoglobulinlike transcripts. Here we observed significantly less HLA-G in plasma from immune thrombocytopenia (ITP) patients positive for anti-platelet autoantibodies compared with autoantibodies-negative patients or healthy controls, while we found that HLA-G is positively correlated with platelet counts in both patients and healthy controls. We also found less membranebound HLA-G and immunoglobulin-like transcripts on CD4+ and CD14+ cells in patients. Recombinant HLA-G upregulated immunoglobulin-like transcript 2 expression on CD4+ and immunoglobulin-like transcript 4 on CD14+ cells. HLA-G upregulated IL-4 and IL-10, and downregulated tumor necrosis factor-a, IL-12 and IL-17 secreted by patient peripheral blood mononuclear cells, suggesting a stimulation of Th2 differentiation and downregulation of Th1 and Th17 immune response. HLA-G-modulated dendritic cells from ITP patients showed decreased expression of CD80 and CD86, and suppressed CD4+ T-cell proliferation compared to unmodulated cells. Moreover, HLA-G-modulated cells from patients induced less platelet apoptosis. HLA-G administration also significantly alleviated thrombocytopenia in a murine model of ITP. In conclusion, our data demonstrated that impaired expression of HLA-G and immunoglobulin-like transcripts is involved in the pathogenesis of ITP; recombinant HLA-G can correct this abnormality via upregulation of immunoglobulin-like transcripts, indicating that HLA-G can be a diagnostic marker and a therapeutic option for ITP.
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http://dx.doi.org/10.3324/haematol.2018.204040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7927897PMC
March 2021

Aberrant expression of microRNA in CD4 cells contributes to Th17/Treg imbalance in primary immune thrombocytopenia.

Thromb Res 2019 May 5;177:70-78. Epub 2019 Mar 5.

Department of Hematology, Qilu Hospital, Shandong University, China. Electronic address:

Introduction: Imbalance of T helper 17 (Th17) cells and regulatory T (Treg) cells occurs in primary immune thrombocytopenia (ITP), but the mechanism remains unclear. We investigated whether expression of microRNAs (miRNAs) related to helper T or Treg cells regulate the Th17/Treg ratio in CD4 T cells.

Materials And Methods: Peripheral blood was obtained from 52 active ITP patients and 56 healthy controls. We detected miRNA expression using RT-PCR with stem-loop primers and U6 as control.Th17 and Treg percentages were analyzed by flow cytometry. CD4 cells were transfected with miRNA (miR-99a, miR-182-5p, miR-183-5p) mimics or inhibitors to investigate their function.

Results: miR-99a expression in CD4 cells in ITP patients was lower than in controls, while expression of miR-182-5p and miR-183-5p were higher in ITP patients. Moreover, Treg percentage correlated positively with miR-99a expression in ITP patients. We found no significant correlation between Th17 percentage and miR-182-5p or miR-183-5p expression. miR-183-5p expression correlated negatively with platelet count, while we found no significant difference between platelet count and miR-99a or miR-182-5p. miR-183-5p expression in CD4 T cells from severe patients was significantly higher than in those from non-severe patients. Furthermore, down-regulating miR-183-5p expression repressed Th17 differentiation, while up-regulating miR-99a increased Tregs detected in CD4 cells from ITP patients. In addition, up-regulated miR-99a repressed mTOR and p-mTOR expression.

Conclusions: miR-99a, miR-182-5p, and miR-183-5p expression levels in CD4 cells were abnormal in ITP patients. Aberrant expression of miRNAs may contribute to the Th17/Treg imbalance in ITP patients and may represent a novel therapeutic target.
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http://dx.doi.org/10.1016/j.thromres.2019.03.005DOI Listing
May 2019

Effects of pyrolysis temperature and addition proportions of corncob on the distribution of products and potential energy recovery during the preparation of sludge activated carbon.

Chemosphere 2019 Apr 8;221:175-183. Epub 2019 Jan 8.

Beijing Key Laboratory for Source Control Technology of Water Pollution, Engineering Research Center for Water Pollution Source Control and Eco-remediation, Beijing Forestry University, Beijing 100083, China. Electronic address:

The potential energy recovery during sludge activated carbon (SAC) preparation by co-pyrolysis of sewage sludge and biomass has recently gained significant attention. This study firstly evaluated the distribution of pyrolysis products including SAC, oils and gases during sludge pyrolysis at different temperatures (400 °C-800 °C) and corncob addition proportions (0-50%, w/w). The results demonstrated that with the increase of pyrolysis temperature, yield of SAC declined dramatically, while yields of pyrolysis oils and gases increased. With increasing addition of corncob, the yields of SAC and pyrolysis oils declined slightly, while the yield of gases generally increased. Then, the potential energy recovery during sludge pyrolysis was calculated, and the highest energy recovery value was 10.21 kJ/g achieved at 800 °C and 50% corncob addition. However, higher pyrolysis temperature over 600 °C resulted in lower yield and iodine adsorption capacity of SAC. Therefore, the suitable conditions were suggested to be at 600 °C with 50% corncob addition considering both adsorption performance of SAC and potential energy recovery efficiency.
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http://dx.doi.org/10.1016/j.chemosphere.2019.01.026DOI Listing
April 2019

Reproductive and developmental toxicity study of caffeic acid in mice.

Food Chem Toxicol 2019 Jan 23;123:106-112. Epub 2018 Oct 23.

Department of Hematology, Qilu Hospital, Shandong University, Jinan, China; Shandong Provincial Key Laboratory of Immunohematology, Qilu Hospital, Shandong University, Jinan, China; Leading Research Group of Scientific Innovation, Department of Science and Technology of Shandong Province, Qilu Hospital, Shandong University, Jinan, China. Electronic address:

Caffeic acid is an antioxidant commonly used to promote hematopoiesis and hemostasis. However, little is known about its systemic safety profile in reproduction and development. Here, we focused on the reproductive and developmental toxicity of caffeic acid in F0 female mice and F1 offspring. In the three-segment study, the F0 female mice were continuously exposed to 0, 0.15, 5 or 150 mg/kg/day of caffeic acid by gavage. We found that 5 mg/kg/day and 150 mg/kg/day of caffeic acid affected implantation of embryos when administered before gestation day 6. In addition, 150 mg/kg/day of caffeic acid affected fetal weight gain. No maternal toxicity, fetal teratogenesis or post-natal effects on pup development were observed. The no-observed-adverse-effect-level was 0.15 mg/kg/day for pregnant mice under the conditions of this study.
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http://dx.doi.org/10.1016/j.fct.2018.10.040DOI Listing
January 2019

Proteasome Inhibition with Bortezomib Induces Apoptosis of Long-Lived Plasma Cells in Steroid-Resistant or Relapsed Immune Thrombocytopaenia.

Thromb Haemost 2018 Oct 20;118(10):1752-1764. Epub 2018 Sep 20.

Department of Haematology, Qilu Hospital, Shandong University, Jinan, China.

Primary immune thrombocytopaenia (ITP) is the most common haemorrhagic disease. Although most patients respond initially to mainstream therapies, such as corticosteroids, immunosuppressants or rituximab, a large proportion of patients fail to respond or relapse. These treatments only affect B lymphocytes or short-lived plasma cells, but not already existing long-lived plasma cells (LLPCs) which persistently secrete antibodies. We hypothesized that LLPCs may play a role in the corticosteroid-resistant or relapsed ITP patients, and bortezomib, a proteasome inhibitor, may act on plasma cells and offer a therapeutic effect. Although a significant difference in the proportion of CD19CD38CD138 total LLPCs was not observed by flow cytometry, a glycoprotein (GP) IIb/IIIa-specific enzyme-linked immunosorbent spot (ELISpot) assay of sorted CD19CD138 LLPCs confirmed the existence of anti-platelet antibody-secreting LLPCs in ITP patients in contrast to healthy controls. Moreover, the LLPCs could be eliminated in the presence of bortezomib by ELISpot assay, which was also confirmed by flow cytometry. Accordingly, a modified monoclonal antibody immobilization of platelet antigen assay of sorted CD19CD138 LLPCs revealed that the concentration of anti-platelet antibodies decreased remarkably when cultured with 0.25 ng/mL bortezomib for 5 days. The apoptosis assay demonstrated that bortezomib could induce apoptosis of LLPCs in a concentration-dependent manner. The proteasome activity assay showed that bortezomib significantly reduced the proteasome activity in sorted CD19CD138 LLPCs. Furthermore, in active ITP murine models, bortezomib eliminated LLPCs in vivo and alleviated thrombocytopaenia. We conclude that LLPCs participate in the pathogenesis of ITP and bortezomib may have potential as a novel therapeutic regimen.
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http://dx.doi.org/10.1055/s-0038-1669921DOI Listing
October 2018

Helicobacter pylori-induced miR-135b-5p promotes cisplatin resistance in gastric cancer.

FASEB J 2019 01 9;33(1):264-274. Epub 2018 Jul 9.

Department of Veterans Affairs, Miami Healthcare System, Miami, Florida, USA.

Helicobacter pylori infection is a major risk factor for the development of gastric cancer. Aberrant expression of microRNAs is strongly implicated in gastric tumorigenesis; however, their contribution in response to H. pylori infection has not been fully elucidated. In this study, we evaluated the expression of miR-135b-5p and its role in gastric cancer. We describe the overexpression of miR-135b-5p in human gastric cancer tissue samples compared with normal tissue samples. Furthermore, we found that miR-135b-5p is also up-regulated in gastric tumors from the trefoil factor 1-knockout mouse model. Infection with H. pylori induced the expression of miR-135b-5p in the in vitro and in vivo models. miR-135b-5p induction was mediated by NF-κB. Treatment of gastric cancer cells with TNF-α induced miR-135b-5p in a NF-κB-dependent manner. Mechanistically, we found that miR-135b-5p targets Krüppel-like factor 4 (KLF4) and binds to its 3' UTR, leading to reduced KLF4 expression. Functionally, high levels of miR-135b-5p suppress apoptosis and induce cisplatin resistance. Our results uncovered a mechanistic link between H. pylori infection and miR-135b-5p-KLF4, suggesting that targeting miR-135b-5p could be a potential therapeutic approach to circumvent resistance to cisplatin.-Shao, L., Chen, Z., Soutto, M., Zhu, S., Lu, H., Romero-Gallo, J., Peek, R., Zhang, S., El-Rifai, W. Helicobacter pylori-induced miR-135b-5p promotes cisplatin resistance in gastric cancer.
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http://dx.doi.org/10.1096/fj.201701456RRDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6355059PMC
January 2019

Methylation of the HOXA10 Promoter Directs miR-196b-5p-Dependent Cell Proliferation and Invasion of Gastric Cancer Cells.

Mol Cancer Res 2018 04 16;16(4):696-706. Epub 2018 Feb 16.

Department of Surgery, University of Miami, Miller School of Medicine, Miami, Florida.

The cross-talk between epigenetics and miRNA expression plays an important role in human tumorigenesis. Herein, the regulation and role of miR-196b-5p in gastric cancer was investigated. qRT-PCR demonstrated that miR-196b-5p is significantly overexpressed in human gastric cancer tissues ( < 0.01). In addition, it was determined that HOXA10, a homeobox family member and host gene for miR-196b-5p, is overexpressed and positively correlated with miR-196b-5p expression levels ( < 0.001). Quantitative pyrosequencing methylation analysis demonstrated significantly lower levels of DNA methylation at the HOXA10 promoter in gastric cancer, as compared with nonneoplastic gastric mucosa specimens. 5-Aza-2'-deoxycytidine treatment confirmed that demethylation of HOXA10 promoter induces the expression of HOXA10 and miR-196b-5p in gastric cancer cell model systems. Using the Tff1 knockout mouse model of gastric neoplasia, hypomethylation and overexpression of HOXA10 and miR-196b-5p in gastric tumors was observed, as compared with normal gastric mucosa from Tff1 wild-type mice. Mechanistically, reconstitution of TFF1 in human gastric cancer cells led to an increased HOXA10 promoter methylation with reduced expression of HOXA10 and miR-196b-5p. Functionally, miR-196b-5p reconstitution promoted human gastric cancer cell proliferation and invasion In summary, the current data demonstrate overexpression of miR-196b-5p in gastric cancer and suggest that TFF1 plays an important role in suppressing the expression of miR-196b-5p by mediating DNA methylation of the HOXA10 promoter. Loss of TFF1 expression may promote proliferation and invasion of gastric cancer cells through induction of promoter hypomethylation and expression of the HOXA10/miR-196b-5p axis. This study indicates that loss of TFF1 promotes the aberrant overexpression of HOXA10 and miR-196b-5p by demethylation of the HOXA10 promoter, which provides a new perspective of TFF1/HOXA10/miR-196b-5p functions in human gastric cancer. .
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http://dx.doi.org/10.1158/1541-7786.MCR-17-0655DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5882501PMC
April 2018

Inflammation-Related Gene Polymorphisms Associated With Primary Immune Thrombocytopenia.

Front Immunol 2017 28;8:744. Epub 2017 Jun 28.

Department of Hematology, Qilu Hospital, Shandong University, Jinan, China.

Primary immune thrombocytopenia (ITP) is an acquired autoimmune disease characterized by a reduced platelet count and an increased risk of bleeding. Although immense research has improved our understanding of ITP, the pathogenesis remains unclear. Here, we investigated the involvement of 25 single-nucleotide polymorphisms (SNPs) of the inflammation-related genes, including , and , in the pathogenesis and treatment response of ITP. We recruited 312 ITP inpatients and 154 healthy participants in this case-control study. Inflammation-related SNP genotyping was performed on the Sequenom MassARRAY iPLEX platform. The expression of TNFAIP3 mRNA was determined by quantitative real-time RT-PCR. All SNPs in healthy controls were consistent with Hardy-Weinberg equilibrium. Statistical analysis revealed that rs10499194 in was significantly associated with a decreased risk of ITP after Bonferroni multiple correction (codominant, CT vs. CC, OR = 0.431, 95% CI = 0.262-0.711,  = 0.001; dominant, TT/CT vs. CC, OR = 0.249, 95% CI = 0.141-0.440,  = 0.000). Besides, expression was significantly higher in patients with CT and pooled CT/TT genotypes compared with CC genotype ( = 0.001;  = 0.001). Interestingly, rs10499194 was also associated with corticosteroid-sensitivity (codominant, CT vs. CC, OR = 0.092, 95% CI = 0.021-0.398,  = 0.001; dominant, TT/CT vs. CC, OR = 0.086, 95% CI = 0.020-0.369,  = 0.001; allelic, T vs. C, OR = 0.088, 95% CI = 0.021-0.372,  = 0.001). Furthermore, no significant association was found between inflammation-related SNPs and the severity or refractoriness of ITP after Bonferroni multiple correction. Our findings suggest that rs10499194 may be a protective factor for susceptibility and corticosteroid sensitivity in ITP patients.
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http://dx.doi.org/10.3389/fimmu.2017.00744DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5487479PMC
June 2017

A novel recombinant human thrombopoietin therapy for the management of immune thrombocytopenia in pregnancy.

Blood 2017 08 19;130(9):1097-1103. Epub 2017 Jun 19.

Department of Hematology, Qilu Hospital, Shandong University, Jinan, China.

The aim of this study was to determine the safety and efficacy of recombinant human thrombopoietin (rhTPO) for the management of immune thrombocytopenia (ITP) during pregnancy. Pregnant patients with ITP were enrolled in the study if they had a platelet count less than 30 × 10/L, were experiencing bleeding manifestations, had failed to respond to corticosteroids and/or intravenous immunoglobulin (IVIG), and had developed refractoriness to platelet transfusion. Thirty-one patients received rhTPO at an initial dose of 300 U/kg once daily for 14 days. Twenty-three patients responded (74.2%), including 10 complete responders (>100 × 10/L) and 13 responders (30-100 × 10/L). It appears that rhTPO ameliorated the bleeding symptoms remarkably, even in the nonresponders. rhTPO was well tolerated. Dizziness, fatigue, and pain at an injection site were reported in 1 patient each. No congenital disease or developmental delays were observed in the infants in a median follow-up of 53 (range, 39-68) weeks. In conclusion, rhTPO is a potentially safe and effective treatment choice for patients with ITP during pregnancy. Our work has paved the way for further study on the clinical application of rhTPO and other thrombopoietic agents for the management of ITP during pregnancy. This study is registered at www.clinicaltrials.gov as NCT02391272.
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http://dx.doi.org/10.1182/blood-2017-01-761262DOI Listing
August 2017

Construction of disease-specific transcriptional regulatory networks identifies co-activation of four gene in esophageal squamous cell carcinoma.

Oncol Rep 2017 Jul 30;38(1):411-417. Epub 2017 May 30.

Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesions of Digestive Disease, Xicheng, Beijing 100050, P.R. China.

Even though various molecules may serve as biomarkers, little is known concerning the mechanisms underlying the carcinogenesis of ESCC, particularly the transcriptional regulatory network. Thus, in the present study, paired ESCC and non-cancerous (NC) tissues were assayed by Affymetrix microarray assays. Passing Attributes between Networks for Data Assimilation (PANDA) was used to construct networks between transcription factors (TFs) and their targets. AnaPANDA program was applied to compare the regulatory networks. A hypergeometric distribution model-based target profile similarity analysis was utilized to find co-activation effects using both TF-target networks and differential expression data. There were 1,116 genes upregulated and 1,301 genes downregulated in ESCC compared with NC tissues. In TF-target networks, 16,970 ESCC-specific edges and 9,307 NC-specific edges were identified. Edge enrichment analysis by AnaPANDA indicated 17 transcription factors (NFE2L2, ELK4, PAX6, TLX1, ESR1, ZNF143, TP53, REL, ELF5, STAT1, TBP, NHLH1, FOXL1, SOX9, STAT3, ELK1, and HOXA5) suppressed in ESCC and 5 (SPIB, BRCA1, MZF1, MAFG and NFE2L1) activated in ESCC. For SPIB, MZF1, MAFG and NFE2L1, a strong and significant co-activation effect among them was detected in ESCC. In conclusion, the construction of transcriptional regulatory networks found SPIB, MZF1, MAFG and NFE2L1 co-activated in ESCC, which provides distinctive insight into the carcinogenesis mechanism of ESCC.
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http://dx.doi.org/10.3892/or.2017.5681DOI Listing
July 2017

Integrated Analysis Identifies Molecular Signatures and Specific Prognostic Factors for Different Gastric Cancer Subtypes.

Transl Oncol 2017 Feb 22;10(1):99-107. Epub 2016 Dec 22.

Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing, 100050, PR China. Electronic address:

Background: Gastric cancer (GC) is the fifth leading cause of cancer-related deaths worldwide. As an effective and easily performed method, microscopy-based Lauren classification has been widely accepted by gastrointestinal surgeons and pathologists for GC subtyping, but molecular characteristics of different Lauren subtypes were poorly revealed.

Methods: GSE62254 was used as a derivation cohort, and GSE15459 was used as a validation cohort. The difference between diffuse and intestinal GC on the gene expression level was measured. Gene ontology (GO) enrichment analysis was performed for both subgroups. Hierarchical clustering and heatmap exhibition were also performed. Kaplan-Meier plot and Cox proportional hazards model were used to evaluate survival grouped by the given genes or hierarchical clusters.

Results: A total of 4598 genes were found differentially expressed between diffuse and intestinal GC. Immunity- and cell adhesion-related GOs were enriched for diffuse GC, whereas DNA repair- and cell cycle-related GOs were enriched for intestinal GC. We proposed a 40-gene signature (χ=30.71, P<.001) that exhibits better discrimination for prognosis than Lauren classification (χ=12.11, P=.002). FRZB [RR (95% CI)=1.824 (1.115-2.986), P=.017] and EFEMP1 [RR (95% CI)=1.537 (0.969-2.437), P=.067] were identified as independent prognostic factors only in diffuse GC but not in intestinal GC patients. KRT23 [RR (95% CI)=1.616 (0.938-2.785), P=.083] was identified as an independent prognostic factor only in intestinal GC patients but not in diffuse GC patients. Similar results were achieved in the validation cohort.

Conclusion: We found that GCs with different Lauren classifications had different molecular characteristics and identified FRZB, EFEMP1, and KRT23 as subtype-specific prognostic factors for GC patients.
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http://dx.doi.org/10.1016/j.tranon.2016.11.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5198736PMC
February 2017

CD8(+) T cells induce platelet clearance in the liver via platelet desialylation in immune thrombocytopenia.

Sci Rep 2016 06 20;6:27445. Epub 2016 Jun 20.

Department of Hematology, Qilu Hospital, Shandong University, Jinan, China.

In addition to antiplatelet autoantibodies, CD8(+) cytotoxic T lymphocytes (CTLs) play an important role in the increased platelet destruction in immune thrombocytopenia (ITP). Recent studies have highlighted that platelet desialylation leads to platelet clearance via hepatocyte asialoglycoprotein receptors (ASGPRs). Whether CD8(+) T cells induce platelet desialylation in ITP remains unclear. Here, we investigated the cytotoxicity of CD8(+) T cells towards platelets and platelet desialylation in ITP. We found that the desialylation of fresh platelets was significantly higher in ITP patients with positive cytotoxicity of CD8(+) T cells than those without cytotoxicity and controls. In vitro, CD8(+) T cells from ITP patients with positive cytotoxicity induced significant platelet desialylation, neuraminidase-1 expression on the platelet surface, and platelet phagocytosis by hepatocytes. To study platelet survival and clearance in vivo, CD61 knockout mice were immunized and their CD8(+) splenocytes were used. Platelets co-cultured with these CD8(+) splenocytes demonstrated decreased survival in the circulation and increased phagocytosis in the liver. Both neuraminidase inhibitor and ASGPRs competitor significantly improved platelet survival and abrogated platelet clearance caused by CD8(+) splenocytes. These findings suggest that CD8(+) T cells induce platelet desialylation and platelet clearance in the liver in ITP, which may be a novel mechanism of ITP.
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http://dx.doi.org/10.1038/srep27445DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4913243PMC
June 2016

Altered cytokine levels in pediatric ITP.

Platelets 2015 25;26(6):589-92. Epub 2015 Mar 25.

Department of Internal Medicine, University of Gothenburg , Gothenburg , Sweden .

Immune thrombocytopenia (ITP) is an autoimmune disease where platelets are destroyed prematurely. In the majority of children, the disease resolves, but in some, it becomes chronic. Cytokines are important mediators of the immune response and are known to be dysregulated in autoimmune diseases. Therefore, our aim was to investigate differences in plasma levels of cytokines between children with ITP and healthy controls. We had two cohorts of children: one Swedish with 18 children with ITP and seven healthy children and a second Chinese one with 58 children with ITP and 30 healthy children. Plasma levels of chemokine (C-X3-C motif) ligand 1 (CX3CL1), transforming growth factor β1 (TGF-β1), and interleukin 22 (IL-22) were analyzed in both cohorts using enzyme-linked immunosorbent assays (ELISAs). We found lower plasma levels of TGF-β1 and elevated levels of CX3CL1 and IL-22 in children with ITP compared with controls in both the Swedish and the Chinese cohort. In conclusion, all three cytokines differ between pediatric ITP and healthy controls and may, therefore, be potential biomarkers for the disease.
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http://dx.doi.org/10.3109/09537104.2014.974526DOI Listing
May 2016

Low-dose decitabine promotes megakaryocyte maturation and platelet production in healthy controls and immune thrombocytopenia.

Thromb Haemost 2015 May 8;113(5):1021-34. Epub 2015 Jan 8.

Ming Hou, Department of Hematology, Qilu Hospital, Shandong University, 107 West Wenhua Road, Jinan, Shandong, 250012, China, Tel.: +86 531 82169879, Fax: +86 531 86927544, E-mail:

Impaired megakaryocyte maturation and insufficient platelet production have been shown to participate in the pathogenesis of immune thrombocytopenia (ITP). Our previous study demonstrated that low expression of tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) in megakaryocytes contributed to impaired platelet production in ITP. Decitabine (DAC), a demethylating agent, is known to promote cell differentiation and maturation at low doses. However, whether decitabine is potential in promoting megakaryocyte maturation and platelet release in ITP is unclear. In this study, we evaluated the effect of DAC on megakaryocyte maturation and platelet release in the presence of ITP plasma that has been shown to cause impaired megakaryocyte maturation and platelet production. We observed that low-dose DAC (10 nM) could significantly increase the number of mature polyploid (≥ 4N) megakaryocytes in cultures with plasma from healthy controls and more than one-half of ITP patients in vitro. Furthermore, the number of platelets released from these megakaryocytes significantly increased compared with those untreated with DAC. In these megakaryocytes, DAC significantly enhanced TRAIL expression via decreasing its promoter methylation status. These findings demonstrate that low-dose DAC can promote megakaryocyte maturation and platelet production and enhance TRAIL expression in megakaryocytes in healthy controls and ITP. The potential therapeutic role of low-dose DAC may be beneficial for thrombocytopenic disorders.
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http://dx.doi.org/10.1160/TH14-04-0342DOI Listing
May 2015

Successful treatment with oseltamivir phosphate in a patient with chronic immune thrombocytopenia positive for anti-GPIb/IX autoantibody.

Platelets 2015 28;26(5):495-7. Epub 2014 Aug 28.

Department of Hematology, Qilu Hospital, Shandong University , Jinan , China .

The management of chronic immune thrombocytopenia (ITP) remains to be a challenge. Oseltamivir phosphate is a sialidase inhibitor agent used to treat influenza in the conventional sense. At present, we demonstrate for the first time that an adult chronic ITP patient with anti-GP Ib/IX autoantibody, who was resistant to corticosteroids, IVIG, recombinant human thrombopoietin, rituximab, danazol and vindesine, but was successfully treated with oseltamivir phosphate. Through flow cytometric analysis of β-galactose and β-GlcNAc exposure on platelet surfaces, we showed that oseltamivir phosphate could reduce the desialylation level of platelet glycoproteins in ITP patient. The substantial alleviation of thrombocytopenia in this case, though not leading to conclusions, lays a foundation for a novel approach for the treatment of ITP.
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http://dx.doi.org/10.3109/09537104.2014.948838DOI Listing
March 2016

Co-production of activated carbon, fuel-gas, and oil from the pyrolysis of corncob mixtures with wet and dried sewage sludge.

Waste Manag Res 2014 Jun;32(6):519-26

Beijing Key Lab for Source Control Technology of Water Pollution, Beijing Forestry University, Beijing, China.

This study explored the amount and composition of pyrolysis gas and oil derived from wet material or dried material during the preparation of sludge-corncob activated carbon, and evaluated the physicochemical and surface properties of the obtained two types of sludge-corncob-activated carbons. For wet material, owing to the presence of water, the yields of sludge-corncob activated carbon and the oil fraction slightly decreased while the yield of gases increased. The main pyrolysis gas compounds were H2 and CO2, and more H2 was released from wet material than dried material, whereas the opposite holds for CO2 Heterocyclics, nitriles, organic acids, and steroids were the major components of pyrolysis oil. Furthermore, the presence of water in wet material reduced the yield of polycyclic aromatic hydrocarbons from 6.76% to 5.43%. The yield of furfural, one of heterocyclics, increased sharply from 3.51% to 21.4%, which could be explained by the enhanced hydrolysis of corncob. In addition, the surface or chemical properties of the two sludge-corncob activated carbons were almost not affected by the moisture content of the raw material, although their mesopore volume and diameter were different. In addition, the adsorption capacities of the two sludge-corncob activated carbons towards Pb and nitrobenzene were nearly identical.
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http://dx.doi.org/10.1177/0734242X14535652DOI Listing
June 2014

Elevated Th22 cells correlated with Th17 cells in peripheral blood of patients with acute myeloid leukemia.

Int J Mol Sci 2014 Jan 27;15(2):1927-45. Epub 2014 Jan 27.

Department of Hematology, Qilu Hospital, Shandong University, Jinan 250012, China.

Acute myeloid leukemia (AML) is a hematological tumor in which progress T helper (Th) subsets including Th22, Th17, and Th1 cells play a pivotal role. However, the role of T helper (Th) subsets in the immune pathogenesis of AML remains unclear. Here, we investigated frequencies of Th22, Th17, pure Th17, and Th1 cells in the peripheral blood (PB) of AML patients. We demonstrated that Th22, Th17, and pure Th17 in newly-diagnosed (ND) and non-complete remission (Non-CR) AML patients and plasma IL-22 in ND AML patients were significantly increased. Retinoid-related orphan receptor C (RORC) expression was significantly elevated in CR and Non-CR AML patients. However, Th1 in ND AML patients and IL-17 in ND, Non-CR or CR AML patients was significantly decreased compared with controls. Moreover, Th22 and IL-22 showed positive correlation with pure Th17, but Th22 showed negative correlation with Th1 in ND AML patients. RORC showed positive correlation with Th22 and approximately positive correlation with pure Th17 in Non-CR patients. PB blast cell showed positive correlation with Th22 and negative correlation with Th1 in ND AML patients. Our results indicate that Th22 and pure Th17 cells conjointly contribute to the pathogenesis of AML and might be promising novel clinical index for AML.
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http://dx.doi.org/10.3390/ijms15021927DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3958830PMC
January 2014

Differences in gene expression and cytokine levels between newly diagnosed and chronic pediatric ITP.

Blood 2013 Sep 18;122(10):1789-92. Epub 2013 Jul 18.

Department of Internal Medicine, University of Gothenburg, Gothenburg, Sweden.

Immune thrombocytopenia (ITP) is an autoimmune disease where platelets are destroyed prematurely. In the majority of children the disease resolves, but in some it becomes chronic. To investigate whether these 2 phases of the disease are molecularly similar or separate entities we performed DNA microarray analysis (GEO accession number: GSE46922) of T-cells from newly diagnosed children and children with chronic ITP. We found complete separation of the gene expression profiles between the 2 phases of the disease. Furthermore, the gene expression levels of several cytokines differed between the 2 phases of the disease. This was also reflected in plasma with increased levels of interleukin (IL)-16 and TNF-related weak inducer of apoptosis and lower levels of IL-4 in newly diagnosed compared with chronic ITP. Thus, our data indicate that chronic ITP in childhood is a separate disease entity, dissimilar in many aspects to the newly diagnosed phase.
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http://dx.doi.org/10.1182/blood-2013-05-502807DOI Listing
September 2013
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