Publications by authors named "Xing Cui"

63 Publications

Characteristics and Environmental Response of White Secondary Mineral Precipitate in the Acid Mine Drainage From Jinduicheng Mine, Shaanxi, China.

Bull Environ Contam Toxicol 2021 Aug 21. Epub 2021 Aug 21.

School of Chemistry and Chemical Engineering, Northwestern Polytechnical University, Xi'an, Shaanxi, 710072, P. R. China.

The study focuses on the white secondary mineral precipitate and its environmental response formed in acid mine drainage (AMD) at Jinduicheng Mine (Shaanxi, China). The mineral composition of white precipitate was characterized by Scanning electron microscopy-energy dispersive spectrometer (SEM-EDS), X-ray photoelectron spectroscopy (XRD), Fourier transform infrared spectroscopy (FT-IR), X-ray photoelectron spectroscopy (XPS), Inductively coupled plasma-atomic emission spectrometer (ICP-AES), chemical quantitative calculation and PHREEQC software. The white precipitate was a kind of amorphous crystal with the characteristics of a fine powder, and its main elements were O, Al, S, F, OH and SO groups. Moreover, by comparing the mole number of chemical elements, the main mineral composition of the white precipitate was closest to basaluminite. The geochemical simulation result of the PHREEQC software verified that the white precipitate was basaluminite. According to the analysis of water quality characteristics of water samples, basaluminite can reduce the ions content in the AMD and enrich Cu, Ni, Mo, Cr and F ions, showing an excellent self-purification capacity of the water body. These results are helpful to improve the understanding of secondary mineral and its environmental response, and are of great significance for the environmental protection and sustainable development of mining area.
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http://dx.doi.org/10.1007/s00128-021-03355-9DOI Listing
August 2021

Design, synthesis and evaluation of tetrahydrocarbazole derivatives as potential hypoglycemic agents.

Bioorg Chem 2021 Jul 17;115:105172. Epub 2021 Jul 17.

State Key Laboratory of Functions and Applications of Medicinal Plants & College of Pharmacy, Guizhou Provincial Engineering Technology Research Center for Chemical Drug R&D, Guizhou Medical University, Guiyang 550004, China. Electronic address:

Two series of tetrahydrocarbazole derivatives have been designed and synthesized based on ZG02, a promising candidate developed in our previous studies. The newly prepared compounds were screened for glucose consumption activity in HepG2 cell lines. Aza-tetrahydrocarbazole compound 12b showed the most potent hypoglycemic activity with a 45% increase in glucose consumption when compared to the solvent control, which had approximately 1.2-fold higher activity than the positive control compounds (metformin and ZG02). An investigation of the potential mechanism indicated that 12b may exhibit hypoglycemic activity via activation of the AMPK pathway. Metabolic stability assays revealed that 12b showed good stability profiles in both artificial gastrointestinal fluids and blood plasma from SD rats. An oral glucose tolerance test (OGTT) was performed and the results further confirmed that 12b was a potent hypoglycemic agent.
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http://dx.doi.org/10.1016/j.bioorg.2021.105172DOI Listing
July 2021

Ginsenoside Rg1 can restore hematopoietic function by inhibiting Bax translocation-mediated mitochondrial apoptosis in aplastic anemia.

Sci Rep 2021 Jun 17;11(1):12742. Epub 2021 Jun 17.

Department of Hematology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, 250014, China.

The present study investigated, the anti-apoptotic activity of Ginsenoside Rg1 (Rg1) via inhibition of Bax translocation and the subsequent recovery of hematopoietic function. Mitochondrial apoptosis in bone marrow mononuclear cells (BMNCs) was observed in aplastic anemia (AA) patients. To establish a mouse model of AA, BALB/c mice were transplanted with lymph node cells from DBA/2 donor mice via vein injection after treatment with Co60 γ-radiation. After treatment with Rg1 for 14 days, the peripheral blood and Lin-Sca-1 + c-Kit + (LSK) cell counts of the treated group were increased compared with those of the untreated model mice. In in vivo and in vitro tests of LSKs, Rg1 was found to increase mitochondrial number and the ratio of Bcl-2/Bax and to decrease damage to the mitochondrial inner and outer membranes, the mitochondrial Bax level and the protein levels of mitochondrial apoptosis-related proteins AIF and Cyt-C by decreasing the ROS level. Rg1 also improved the concentration-time curve of MAO and COX and levels of ATP, ADP and AMP in an in vitro test. In addition, high levels of Bax mitochondrial translocation could be corrected by Rg1 treatment. Levels of markers of mitochondrial apoptosis in the Rg1-treated group were significantly better than those in the AA model group, implying that Rg1 might improve hematopoietic stem cells and thereby restore hematopoietic function in AA by suppressing the mitochondrial apoptosis mediated by Bax translocation.
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http://dx.doi.org/10.1038/s41598-021-91471-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8211841PMC
June 2021

Exosomal circRNA as a novel potential therapeutic target for multiple myeloma-related myocardial damage.

Cancer Cell Int 2021 Jun 13;21(1):311. Epub 2021 Jun 13.

Department of Hematology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, 16369 Jingshi Road, Jinan, 250014, China.

Introduction: Myocardial damage is a mostly incurable complication of multiple myeloma (MM) that seriously affects the treatment outcome and quality of life of patients. Exosomal circular RNAs (exo-circRNAs) play an important role in tumor occurrence and development and are considered key factors in MM pathogenesis. However, the role and mechanism of action of exo-circRNAs in MM-related myocardial damage are still unclear. This study aimed to investigate correlations between exo-circRNAs and MM and to preliminarily explore the role of exo-circRNAs in MM-related myocardial damage.

Methods: Six MM patients and five healthy controls (HCs) were included in the study. High-throughput sequencing and qRT-PCR verification were used to obtain a profile of abnormally expressed exo-circRNAs. GO, KEGG, miRanda, TargetScan and Metascape were used for bioinformatics analyses. H9C2 cells treated with exosomes from U266 cells were used in cell experiments. CCK-8, PCR, immunofluorescence and western blotting assays were used to detect cell proliferation and expression of autophagy-related indicators. Electron microscopy was used to observe the number of autophagic vesicles.

Results: Bioinformatics analysis showed that circRNAs with upregulated expression had the potential to promote MM-related myocardial damage. In addition, PCR results confirmed that circ-G042080 was abundantly expressed in the serum exosomes of 20 MM patients. Correlation analysis showed that the expression level of circ-G042080 was positively correlated with the clinical level of MM and MM-related myocardial damage and that circ-G042080 might interfere with MM-related myocardial damage through a downstream miRNA/TLR4 axis. Cell experiments demonstrated that the circ-G042080/hsa-miR-4268/TLR4 axis might exist in H9C2 cells incubated with exosomes and cause abnormal autophagy.

Conclusion: Abnormal expression of serum exo-circRNAs was found to be associated with MM-related myocardial damage, suggesting that exo-circRNAs might become a new diagnostic marker of MM-related myocardial damage and a therapeutic target.
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http://dx.doi.org/10.1186/s12935-021-02011-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8201884PMC
June 2021

[Research Advance of Autophagy in Acute Intestinal Graft-Versus-Host Disease--Review].

Zhongguo Shi Yan Xue Ye Xue Za Zhi 2021 Jun;29(3):998-1001

College of Chinese Medicine , Shandong University of Traditional Chinese Medicine; Jinan 250011, Shandong Province, China,E-mail:

Acute intestinal graft-versus-host disease is a refractory disease which can affect implantation and become a threat to life in severe cases. Autophagy is an intracellular degradation pathway necessary for maintaining cellular energy homeostasis. In recent years, a large number of studies have found that it is closely related to the pathogenesis and process of acute intestinal graft-versus-host disease. The main mechanisms may involve that inflammatory factor storm after pretreatment and infusion of donor cells induces disordered intestinal immune tolerance, and abnormal oxidative stress damages intestinal mucosal barrier, leading to intestinal rejection of acute graft-versus-host disease via mTOR signal pathway of autophagy, disordered mitophagy and other related pathways.
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http://dx.doi.org/10.19746/j.cnki.issn.1009-2137.2021.03.055DOI Listing
June 2021

Membrane-Bound Transcriptional Activator NTL1 from Rapeseed Positively Modulates Leaf Senescence through Targeting Genes Involved in Reactive Oxygen Species Production and Programmed Cell Death.

J Agric Food Chem 2021 May 20;69(17):4968-4980. Epub 2021 Apr 20.

State Key Laboratory of Crop Stress Biology for Arid Areas and, College of Life Sciences, Northwest A & F University, Yangling, Shaanxi 712100, China.

Leaf senescence is the last stage of leaf development and is determined by various environmental and endogenous signals. Leaf senescence can determine plant productivity and fitness. Transcription factors (TFs) with the transmembrane domain constitute a special group of regulatory proteins that can translocate from the membrane system into nuclei to exert the transcriptional function upon endogenous or exogenous stimuli. Reactive oxygen species (ROSs) play an important role in numerous processes throughout the life cycle of plants including leaf senescence. Leaf senescence is characterized by massive programmed cell death (PCD) and is a type of developmental PCD. The transcriptional regulatory relationships between membrane-bound TFs and leaf senescence remain largely uncharacterized, especially in rapeseed ( L.), an important oil crop. Here, we show that BnaNTL1 is a membrane-bound NAC (NAM, ATAF, and CUC) TF, which is predominantly expressed in senescent leaves. Expression of , a form of BnaNTL1 devoid of the transmembrane domain, can induce serious HR-like cell death symptoms and ROS accumulation in cells. Plants overexpressing show earlier leaf senescence compared with the control, accompanied by chlorophyll degradation and electrolyte leakage. Genes involved in ROS production (), PCD ( and ), and leaf senescence () are significantly induced and activated by BnaNTL1ΔTM according to the quantitative reverse transcription PCR (qRT-PCR) analysis and dual luciferase reporter (Dual-LUC) assay. Moreover, electrophoretic mobility shift assay revealed that BnaNTL1 directly bound to the NTLBS elements in promoters of , , and . In conclusion, these results demonstrate that BnaNTL1 positively modulates ROS production and HR-like cell death to induce leaf senescence.
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http://dx.doi.org/10.1021/acs.jafc.1c00182DOI Listing
May 2021

Can peritumoral regions increase the efficiency of machine-learning prediction of pathological invasiveness in lung adenocarcinoma manifesting as ground-glass nodules?

J Thorac Dis 2021 Mar;13(3):1327-1337

Department of Radiology, Changzheng Hospital, Naval Medical University, Shanghai, China.

Background: The peri-tumor microenvironment plays an important role in the occurrence, growth and metastasis of cancer. The aim of this study is to explore the value and application of a CT image-based deep learning model of tumors and peri-tumors in predicting the invasiveness of ground-glass nodules (GGNs).

Methods: Preoperative thin-section chest CT images were reviewed retrospectively in 622 patients with a total of 687 pulmonary GGNs. GGNs are classified according to clinical management strategies as invasive lesions (IAC) and non-invasive lesions (AAH, AIS and MIA). The two volumes of interest (VOIs) identified on CT were the gross tumor volume (GTV) and the gross volume of tumor incorporating peritumoral region (GPTV). Three dimensional (3D) DenseNet was used to model and predict GGN invasiveness, and five-fold cross validation was performed. We used GTV and GPTV as inputs for the comparison model. Prediction performance was evaluated by sensitivity, specificity, and area under the receiver operating characteristic curve (AUC).

Results: The GTV-based model was able to successfully predict GGN invasiveness, with an AUC of 0.921 (95% CI, 0.896-0.937). Using GPTV, the AUC of the model increased to 0.955 (95% CI, 0.939-0.971).

Conclusions: The deep learning method performed well in predicting GGN invasiveness. The predictive ability of the GPTV-based model was more effective than that of the GTV-based model.
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http://dx.doi.org/10.21037/jtd-20-2981DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024795PMC
March 2021

IL‑33/ST2 promotes the malignant progression of gastric cancer via the MAPK pathway.

Mol Med Rep 2021 05 24;23(5). Epub 2021 Mar 24.

Department of Clinical Laboratory, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250012, P.R. China.

Gastric cancer (GC) remains one of the commonest malignant tumors and the second leading cause of cancer‑related deaths worldwide. IL‑33 is highly expressed in tumor tissues and serum of patients with GC. However, the function of the IL‑33 and IL‑33 receptor ST2 in the malignant progression of GC is yet to be elucidated. The present study aimed to explore the effect of the IL‑33/ST2 axis on the biological functions of GC cells. The expression of ST2 in GC tissues was measured by immunohistochemistry. GC cell lines (AGS and MKN45) were treated with IL‑33, and the expression of ST2 was downregulated by using specific siRNA. The effects of the IL‑33/ST2 axis on cell proliferation, migration, invasion, cell cycle and apoptosis was detected by CCK8, Transwell, wound healing, flow cytometry and western blotting assays. The present study found that ST2 was highly expressed in GC tissues compared with normal tissues. IL‑33 promoted the proliferation and cell cycle progression of GC cells, and upregulated the expression levels of CDK4, CDK6 and cyclin D1. Furthermore, IL‑33 inhibited the apoptosis of GC cells and regulated the expression of apoptosis‑associated proteins. In addition, IL‑33 stimulated the invasion and migration of GC cells. However, the transfection of ST2 small interfering (si)RNA attenuated the effects of IL‑33. Finally, IL‑33 stimulation increased the phosphorylation levels of ERK1/2, JNK and p38. The transfection of ST2 siRNA could significantly inhibit the IL‑33‑induced ERK1/2, JNK and p38 activation. In conclusion, it was found that ST2 was highly expressed in GC tissues. IL‑33/ST2 promoted the malignant progression of GC cells by inducing the activation of ERK1/2, JNK and p38.
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http://dx.doi.org/10.3892/mmr.2021.12000DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7985998PMC
May 2021

Poor Prognosis of Pulmonary Adenosquamous Carcinoma with and Double Mutation.

Onco Targets Ther 2021 17;14:1113-1116. Epub 2021 Feb 17.

Department of Internal Medicine, The First Hospital of Xingtai, Xingtai, People's Republic of China.

RAS mutations constitute one of the major tumorigenic mechanisms and are detected in approximately 20% of lung cancers. The most frequent mutated and well-studied RAS isoform is , which is associated with an overall poor prognosis in non-small-cell lung cancer (NSCLC). However, the clinical significances of and in NSCLC are rarely reported. Here, we present a 58-year-old male smoker who was diagnosed with stage IV lung adenosquamous carcinoma. A rare and double mutation was detected in the primary tumor and lymph node samples using next-generation sequencing (NGS). The patient showed rapid disease progression and passed away due to respiratory failure after 15 days of osimertinib in combination with cisplatin. To the best of our knowledge, this is the first report associating and double mutation in the poor prognosis of NSCLC.
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http://dx.doi.org/10.2147/OTT.S295813DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7898223PMC
February 2021

Exosomal circRNA as a novel potential therapeutic target for multiple myeloma-related peripheral neuropathy.

Cell Signal 2021 02 5;78:109872. Epub 2020 Dec 5.

Department of Hematology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, 16369 Jingshi Road, Jinan 250014, China. Electronic address:

Peripheral neuropathy (PN) is an incurable complication of multiple myeloma (MM) which adversely affects patients' quality of life. The important roles that Circular RNAs (circRNAs) play in tumor progression, and exosome-mediated intracellular communication has been recognized as a crucial factor in the pathogenesis of MM. However, the role of exosome-derived circRNAs (exo-circRNAs) in MM and MM-induced PN remains elusive. In this study, we aimed to investigate the correlation between serum exo-circRNAs and MM to preliminarily explore the role of exo-circRNAs in MM-related PN. A cohort of 25 MM patients and 5 healthy control (HC) individuals were enrolled in the study. High-throughput sequencing and qRT PCR validation of serum exo-circRNAs were used to generate the aberrantly expressed exo-circRNAs profiles. Bioinformatics analysis was done using GO, KEGG, miRanda, Targetscan and Metascape. Correlation analysis was conducted between chr2:2744228-2,744,407+ and clinical characteristics of PN. ROC curve, univariate and multivariate COX regression models were conducted to identify the prognostic potential of chr2:2744228-2,744,407+ in the MM-related PN. 265 upregulated circRNAs and 787 downregulated circRNAs, with at least a two-fold difference in expression level in MM patients vs HC, were screened. Bioinformatics analysis indicated that upregulated circRNAs had the potential to facilitate MM-related PN. Furthermore, PCR validated the abundant expression of chr2:2744228-2,744,407+ in the serum exosomes of 25 MM patients. Bioinformatics analysis indicated that chr2:2744228-2,744,407+ might induce MM related PN via the downstream miRNA and GRIN2B axis. Overexpressed chr2:2744228-2,744,407+ in the serum exosomes of MM patients might lead to the downregulation of hsa-miR-6829-3p, elevation of GRIN2B in the serum and PC12 cells, and inhibited cell viability. The correlation analysis indicated that the expression of chr 2:2744228-2,744,407+ was positively correlated with the clinical characteristics of PN. ROC curve, univariate and multivariate COX regression analysis identified that chr2:2744228-2,744,407+ is an independent prognostic factor in the MM related PN. We identified that the abnormal expression of the serum exo-circRNA was correlated with MM-related PN, implying that exo-circRNA has potential as a novel therapeutic target for MM related PN.
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http://dx.doi.org/10.1016/j.cellsig.2020.109872DOI Listing
February 2021

Homoharringtonine Exerts an Antimyeloma Effect by Promoting Excess Parkin-Dependent Mitophagy.

Drug Des Devel Ther 2020 5;14:4749-4763. Epub 2020 Nov 5.

Department of Hematology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, People's Republic of China.

Purpose: Homoharringtonine (HHT) has been used as an antileukemia agent in the clinic which processes a high-potential therapeutic efficacy against multiple myeloma (MM). In this study, we investigated the antimyeloma mechanism of HHT.

Methods: Three MM cell lines and a xenograft model were applied. Mitochondrial function was evaluated by detecting MitoTracker Green, the mtDNA copy number, mitochondrial protein and enzyme activity, the mitochondrial membrane potential and mitochondrial morphology. Mitophagy levels were assessed by monitoring autophagosomes, performing a colocalization analysis and determining the levels of related proteins. An shRNA was applied to knockdown .

Results: Based on the results of the in vitro experiments, HHT exerted a promising antiproliferative effect on the MM.1S, RPMI 8226 and H929 cell lines by increasing mitophagy. In addition, HHT markedly inhibited myeloma tumor growth and prolonged survival by promoting mitophagy in vivo. Furthermore, HHT treatment contributed to notable mitochondrial dysfunction and Parkin-dependent mitophagy, as evidenced by the destruction of mitochondria, the decrease in the mtDNA copy number, decrease in the Bcl-2/Bax ratio, and decrease in the levels of mitochondrial proteins and the optimal expression of Parkin and NDP52. However, the addition of rapamycin did not produce significant synergistic effect with HHT, indicating that HHT reached the threshold level to induce mitophagy. The colocalization analysis and assessment of mitochondrial function examination further confirmed that HHT triggered mitophagy and mitochondrial dysfunction. Moreover, the antiproliferative effect of HHT was reversed by an shRNA targeting , highlighting the indispensable role of Parkin-dependent mitophagy in the antimyeloma effect of HHT.

Conclusion: HHT exerts an antimyeloma effect by inducing excess mitophagy, providing new mechanistic insights into a therapeutic strategy for MM.
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http://dx.doi.org/10.2147/DDDT.S279054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7652225PMC
August 2021

Ectopic overexpression of a membrane-tethered transcription factor gene NAC60 from oilseed rape positively modulates programmed cell death and age-triggered leaf senescence.

Plant J 2021 02 24;105(3):600-618. Epub 2020 Nov 24.

State Key Laboratory of Crop Stress Biology for Arid Areas, College of Life Sciences, Northwest A & F University, Yangling, Shaanxi, 712100, China.

Senescence is an integrative final stage of plant development that is governed by internal and external cues. The NAM, ATAF1/2, CUC2 (NAC) transcription factor (TF) family is specific to plants and membrane-tethered NAC TFs (MTTFs) constitute a unique and sophisticated mechanism in stress responses and development. However, the function of MTTFs in oilseed rape (Brassica napus L.) remains unknown. Here, we report that BnaNAC60 is an MTTF associated with the endoplasmic reticulum (ER) membrane. Expression of BnaNAC60 was induced during the progression of leaf senescence. Translocation of BnaNAC60 into nuclei was induced by ER stress and oxidative stress treatments. It binds to the NTLBS motif, rather than the canonical NAC recognition site. Overexpression of BnaNAC60 devoid of the transmembrane domain, but not the full-length BnaNAC60, induces significant reactive oxygen species (ROS) accumulation and hypersensitive response-like cell death in both tobacco (Nicotiana benthamiana) and oilseed rape protoplasts. Moreover, ectopic overexpression of BnaNAC60 devoid of the transmembrane domain, but not the full-length BnaNAC60, in Arabidopsis also induces precocious leaf senescence. Furthermore, screening and expression profiling identified an array of functional genes that are significantly induced by BnaNAC60 expression. Further it was found that BnaNAC60 can activate the promoter activities of BnaNYC1, BnaRbohD, BnaBFN1, BnaZAT12, and multiple BnaVPEs in a dual-luciferase reporter assay. Electrophoretic mobility shift assay and chromatin immunoprecipitation coupled to quantitative PCR assays revealed that BnaNAC60 directly binds to the promoter regions of these downstream target genes. To summarize, our data show that BnaNAC60 is an MTTF that modulates cell death, ROS accumulation, and leaf senescence.
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http://dx.doi.org/10.1111/tpj.15057DOI Listing
February 2021

WRKY55 transcription factor positively regulates leaf senescence and the defense response by modulating the transcription of genes implicated in the biosynthesis of reactive oxygen species and salicylic acid in .

Development 2020 08 18;147(16). Epub 2020 Aug 18.

State Key Laboratory of Soil Erosion and Dryland Farming on the Loess Plateau, College of Life Sciences, Northwest A&F University, Yangling, Shaanxi 712100, China

Reactive oxygen species (ROS) and salicylic acid (SA) are two factors regulating leaf senescence and defense against pathogens. However, how a single gene integrates both ROS and SA pathways remains poorly understood. Here, we show that WRKY55 transcription factor positively regulates ROS and SA accumulation, and thus leaf senescence and resistance against the bacterial pathogen is predominantly expressed in senescent leaves and encodes a transcriptional activator localized to nuclei. Both inducible and constitutive overexpression of accelerates leaf senescence, whereas mutants delay it. Transcriptomic sequencing identified 1448 differentially expressed genes, of which 1157 genes are upregulated by expression. Accordingly, the ROS and SA contents in -overexpressing plants are higher than those in control plants, whereas the opposite occurs in mutants. Moreover, WRKY55 positively regulates defense against Finally, we show that WRKY55 activates the expression of , , and by binding directly to the W-box-containing fragments. Taken together, our work has identified a new WRKY transcription factor that integrates both ROS and SA pathways to regulate leaf senescence and pathogen resistance.
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http://dx.doi.org/10.1242/dev.189647DOI Listing
August 2020

WRKY42 transcription factor positively regulates leaf senescence through modulating SA and ROS synthesis in Arabidopsis thaliana.

Plant J 2020 09 29;104(1):171-184. Epub 2020 Jul 29.

State Key Laboratory of Crop Stress Biology for Arid Areas, College of Life Sciences, Northwest A & F University, Yangling, Shaanxi, 712100, China.

Leaf senescence represents the final stage of leaf growth and development, and its onset and progression are strictly regulated; however, the underlying regulatory mechanisms remain largely unknown. In this study we found that WRKY42 was highly induced during leaf senescence. Loss-of-function wrky42 mutants showed delayed leaf senescence whereas the overexpression of WRKY42 accelerated senescence. Transcriptome analysis revealed 2721 differentially expressed genes between wild-type and WRKY42-overexpressing plants, including genes involved in salicylic acid (SA) and reactive oxygen species (ROS) synthesis as well as several senescence-associated genes (SAGs). Moreover, WRKY42 activated the transcription of isochorismate synthase 1 (ICS1), respiratory burst oxidase homolog F (RbohF) and a few SAG genes. Consistently, the expression of these genes was reduced in wrky42 mutants but was markedly increased in transgenic Arabidopsis overexpressing WRKY42. Both in vitro electrophoretic mobility shift assays (EMSAs) and in vivo chromatin immunoprecipitation and dual luciferase assays demonstrated that WRKY42 directly bound to the promoters of ICS1 and RbohF, as well as a few SAGs, to activate their expression. Genetic analysis further showed that mutations of ICS1 and RbohF suppressed the early senescence phenotype evoked by WRKY42 overexpression. Thus, we have identified WRKY42 as a novel transcription factor positively regulating leaf senescence by directly activating the transcription of ICS1, RbohF and SAGs, without any seed yield penalty.
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http://dx.doi.org/10.1111/tpj.14914DOI Listing
September 2020

Angelica sinensis polysaccharide prevents mitochondrial apoptosis by regulating the Treg/Th17 ratio in aplastic anemia.

BMC Complement Med Ther 2020 Jun 22;20(1):192. Epub 2020 Jun 22.

Department of Hematology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, 16369 Jingshi Road, Jinan, 250014, China.

Background: Angelica sinensis polysaccharide (ASP) is an effective medicine for aplastic anemia (AA). The present study aims to investigate whether mitochondrial apoptosis in aplastic anemia could be corrected by ASP by adjusting an abnormal level of regulatory T cell (Treg)/ IL-17 secreting CD4 T cell (Th17) ratio.

Methods: BALB/c mice were treated with 5.0 Gy Co60 γ -radiation. Then 2 × 10 lymph node cells from DBA/2 donor mice were transplanted within 4 h after radiation. The mice in the various groups were fed saline or ASP for 2 weeks. For the in vitro experiment, bone marrow nucleated cells (BMNCs) and Treg cells were sorted from the mice on the 2nd day of modeling, and then cultured with or without ASP.

Results: The mice treated with the medium dose of ASP for 14 days showed increased white blood cell (WBC), red blood cell (RBC), platelet (PLT), BMNC counts and Lin-Sca-1 + c-Kit+ (LSK) populations viability compared with the mice in the AA group mice. The data showed that ASP decreased damage to the mitochondrial outer membrane, improved the stabilization of the mitochondrial membrane, and corrected the abnormal levels of ROS and mitochondrial-associated apoptosis proteins, including the Bcl-2/Bax ratio and caspase-3 and caspase-9 expression, in BMNCs which were sorted from the bone marrow cells of AA mice. The changes to the p-P38/P38 and Treg/Th17 ratios induced by AA were also reversed by the medium dose of ASP. The same ASP effect including the Bcl-2/Bax and p-P38/P38 ratio, caspase-3 and caspase-9 expression of BMNCs were observed in vivo. The viability of Treg cells were increased by treatment of ASP in vivo.

Conclusions: ASP might prevent mitochondrial apoptosis to restore the function of hematopoietic stem cells by suppressing abnormal T-cell immunity in AA.
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http://dx.doi.org/10.1186/s12906-020-02995-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7309996PMC
June 2020

Deep residual nets model for staging liver fibrosis on plain CT images.

Int J Comput Assist Radiol Surg 2020 Aug 16;15(8):1399-1406. Epub 2020 Jun 16.

Department of Radiology, Shengjing Hospital of China Medical University, No. 36, Sanhao Street, Heping District, Shenyang, 110004, Liaoning, China.

Purpose: The early diagnosis of liver fibrosis is crucial for the prevention of liver cirrhosis and liver cancer. As gold standard for staging liver fibrosis, liver biopsy is an invasive procedure that carries the risk of serious complications. The aim of this study was to evaluate the performance of the residual neural network (ResNet), a non-invasive methods, for staging liver fibrosis using plain CT images.

Methods: This retrospective study involved 347 patients subjected to liver CT scanning and liver biopsy. For each patient, we selected three axial images adjacent to the puncture location in the eighth or ninth inter-space on the right side. After processing and enhancement (rotation, translation, and amplification), these images were used as input data for the ResNet model. The model used a fivefold cross-validation method. In each fold, the images of approximately 80% of the total sample size (278 patients) were used for training the ResNet model, the other 20% (69 patients) were used for testing the trained network, with the liver biopsy pathology results as gold standard. The proportion of patients in each fibrosis stage was equal for training and test groups. The final result was the mean of the fivefold cross-validation in the test group. The performance of the ResNet model was evaluated for the test group by receiver operating characteristic (ROC) analysis.

Results: For the ResNet model, the area under the ROC curve (AUC) for assessing cirrhosis (F4), advanced fibrosis (F3 or higher), significant fibrosis (F2 or higher), and mild fibrosis (F1 or higher) was 0.97, 0.94, 0.90, and 0.91, respectively.

Conclusions: The ResNet model analysis of plain CT images exhibited high diagnostic efficiency for liver fibrosis staging. As a convenient, fast, and economical non-invasive diagnostic method, the ResNet model can be used to assist radiologists and clinicians in liver fibrosis evaluations.
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http://dx.doi.org/10.1007/s11548-020-02206-yDOI Listing
August 2020

A Rapeseed WRKY Transcription Factor Phosphorylated by CPK Modulates Cell Death and Leaf Senescence by Regulating the Expression of ROS and SA-Synthesis-Related Genes.

J Agric Food Chem 2020 Jul 6;68(28):7348-7359. Epub 2020 Jul 6.

State Key Laboratory of Crop Stress Biology in Arid Areas, College of Life Sciences, Northwest A & F University, Yangling, Shaanxi 712100, China.

Salicylic acid (SA) and reactive oxygen species (ROS) are two well-defined inducers of leaf senescence. Here, we identified a novel WRKY transcription factor gene () in (rapeseed) in promoting SA and ROS production, which eventually led to leaf senescence thereafter. Its expression increased in senescing leaves. Ca-dependent protein kinase (CPK) 5 and -6 interacted with and phosphorylated BnaWSR1. Overexpression of phosphomimic () in rapeseed protoplasts elicited ROS production and cell death while its ectopic expression in enhanced SA and ROS levels and, hence, accelerated leaf senescence. Furthermore, BnaWSR1ca activated the expression of (), () , and (). Electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation-quantitative PCR (ChIP-qPCR) assays demonstrated that BnaWSR1ca directly bound to promoter regions of , , and These data have identified a CPK-WSR1 module that integrates SA and ROS to control cell death and leaf senescence.
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http://dx.doi.org/10.1021/acs.jafc.0c02500DOI Listing
July 2020

[Reaserch Progress on Non-Coding RNA in Multiple Myeloma --Review].

Zhongguo Shi Yan Xue Ye Xue Za Zhi 2020 Apr;28(2):713-716

Department of Hematology,Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250000, Shandong Province,

It is found that non-coding RNAs (ncRNA) plays an important role in the development and treatment of multiple myeloma (MM). For example, some microRNAs (miRNAs) can regulate gene expression, affect autophagy, apoptosis and other physiological and pathological processes, affect synthesis of protein, etc., thus providing a basis for diagnosis, treatment and prognosis of MM evaluation. Long-chain non-coding RNA (Long noncoding RNA, lncRNA) can participate in cell differentiation, bind transcription factors to modify histones, specifically regulate the genome, etc., thus providing potential therapeutic targets for MM patients. While circular RNA (CircRNA) possesses post-transcriptional regulation on function and gene expression, thereby inhibiting the cell activity and proliferation of MM, further inducing apoptosis. In this reviews the functional characteristics of different non-coding RNAs and their research progress in multiple myeloma are summarized briefly.
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http://dx.doi.org/10.19746/j.cnki.issn.1009-2137.2020.02.061DOI Listing
April 2020

Development and validation of a radiomics model based on T2WI images for preoperative prediction of microsatellite instability status in rectal cancer: Study Protocol Clinical Trial (SPIRIT Compliant).

Medicine (Baltimore) 2020 Mar;99(10):e19428

Department of Radiology, West China Hospital, Sichuan University, Chengdu.

Introduction: Globally, colorectal cancer (CRC) is the third most commonly diagnosed cancer in males and the second in females. Rectal cancer (RC) accounts for about 28% of all newly diagnosed CRC cases. The treatment of choice for locally advanced RC is a combination of surgical resection and chemotherapy and/or radiotherapy. These patients can potentially be cured, but the clinical outcome depends on the tumor biology. Microsatellite instability (MSI) is an important biomarker in CRC, with crucial diagnostic, prognostic, and predictive implications. It is important to develop a noninvasive, repeatable, and reproducible method to reflect the microsatellite status. Magnetic resonance imaging (MRI) has been recommended as the preferred imaging examination for RC in clinical practice by both the National Comprehensive Cancer Network and the European Society for Medical Oncology guidelines. T2WI is the core sequence of MRI scanning protocol for RC. Radiomics, the high-throughput mining of quantitative image features from standard-of-care medical imaging that enables data to be extracted and applied within clinical-decision support systems to improve diagnostic, prognostic, and predictive accuracy, is gaining importance in cancer research.We proposed a hypothesis: A simple radiomics model based on only T2WI images can accurately evaluate the MSI status of RC preoperatively.

Objective: To develop a radiomics model based on T2WI images for accurate preoperative diagnosis the MSI status of RC.

Method: All patients with RC were retrospectively enrolled. The dataset was randomly split into training cohort (70% of all patients) and testing cohort (30% of all patients). The radiomics features will be extracted from T2WI-MR images of the entire primary tumor region. Least absolute shrinkage and selection operator was used to select the most predictive radiomics features. Logistic regression models were constructed in the training/validation cohort to discriminate the MSI status using clinical factors, radiomics features, or their integration. The diagnostic performance of these 3 models was evaluated in the testing cohort based on their area under the curve, sensitivity, specificity, and accuracy.

Discussion: This study will help us know whether radiomics model based on T2WI images to preoperative identify MSI status of RC.
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http://dx.doi.org/10.1097/MD.0000000000019428DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7478495PMC
March 2020

Lymph Node Metastasis and Recurrence in Primary Small Cell Carcinoma of the Esophagus: A Retrospective Study of 125 Cases.

Cancer Biother Radiopharm 2019 Sep 23;34(7):459-463. Epub 2019 May 23.

Department of Thoracic Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, P.R. China.

The aim of this study was to investigate and analyze the prognostic factors affecting lymph node (LN) metastasis and postoperative recurrence in patients with primary small cell carcinoma of the esophagus (SCCE). A total of 125 primary SCCE patients who received surgical resection in the Fourth Hospital of Hebei Medical University between March 2005 and August 2009 were included in this retrospective study. All the potential prognostic variables, including the patients' characteristics, tumor features, and treatment modalities, were analyzed by a Cox regression model to explore LN metastasis and the factors associated with postoperative recurrence. LN metastasis rate was significantly correlated with depth of tumor invasion ( < 0.001) and tumor length ( = 0.006). LN metastasis ratio was positively correlated with pathological type ( < 0.001), tumor location ( = 0.002), depth of tumor invasion ( < 0.001), and tumor length ( < 0.001). LN stage and chemotherapy were found to be the independent risk factors for progression-free survival (PFS). Depth of tumor invasion and tumor length were main factors associated with LN metastasis in primary SCCE. The stage of LN metastasis and chemotherapy was independent factors affecting the postoperative PFS.
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http://dx.doi.org/10.1089/cbr.2019.2800DOI Listing
September 2019

Enantioseparation of flurbiprofen enantiomers using chiral ionic liquids by liquid-liquid extraction.

Chirality 2019 Jun 7;31(6):457-467. Epub 2019 May 7.

School of Chemical and Process Engineering, University of Leeds, Leeds, UK.

Flurbiprofen is a kind of nonsteroidal anti-inflammatory drug, which has been widely used in clinic for treatment of rheumatoid arthritis and osteoarthritis. It has been reported that S-flurbiprofen shows good performance on clinic anti-inflammatory treatment, while R-enantiomer almost has no pharmacological activities. It has important practical values to obtain optically pure S-flurbiprofen. In this work, chiral ionic liquids, which have good structural designability and chiral recognize ability, were selected as the extraction selector by the assistance of quantum chemistry calculations. The distribution behaviors of flurbiprofen enantiomers were investigated in the extraction system, which was composed of organic solvent and aqueous phase containing chiral ionic liquid. The results show that maximum enantioselectivity up to 1.20 was attained at pH 2.0, 25°C using 1,2-dichloroethane as organic solvent, 1-butyl-3-methylimidazole L-tryptophan ([Bmim][L-trp]) as chiral selector. The racemic flurbiprofen initial concentration was 0.2 mmol L , and [Bmim][L-trp] concentration was 0.02 mol L . Furthermore, the recycle of chiral ionic liquids has been achieved by reverse extraction process of the aqueous phase with chiral selector, which is significant for industrial application of chiral ionic liquids and scale-up of the extraction process.
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http://dx.doi.org/10.1002/chir.23071DOI Listing
June 2019

The Role of CXCR3 in Neurological Diseases.

Curr Neuropharmacol 2019 ;17(2):142-150

Anesthesiology Institute, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Background: Neurological diseases have become an obvious challenge due to insufficient therapeutic intervention. Therefore, novel drugs for various neurological disorders are in desperate need. Recently, compelling evidence has demonstrated that chemokine receptor CXCR3, which is a G protein-coupled receptor in the CXC chemokine receptor family, may play a pivotal role in the development of neurological diseases. The aim of this review is to provide evidence for the potential of CXCR3 as a therapeutic target for neurological diseases.

Methods: English journal articles that focused on the invovlement of CXCR3 in neurological diseases were searched via PubMed up to May 2017. Moreover, reference lists from identified articles were included for overviews.

Results: The expression level of CXCR3 in T cells was significantly elevated in several neurological diseases, including multiple sclerosis (MS), glioma, Alzheimer's disease (AD), chronic pain, human T-lymphotropic virus type 1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and bipolar disorder. CXCR3 antagonists showed therapeutic effects in these neurological diseases.

Conclusion: These studies provided hard evidence that CXCR3 plays a vital role in the pathogenesis of MS, glioma, AD, chronic pain, HAM/TSP and bipolar disorder. CXCR3 is a crucial molecule in neuroinflammatory and neurodegenerative diseases. It regulates the activation of infiltrating cells and resident immune cells. However, the exact functions of CXCR3 in neurological diseases are inconclusive. Thus, it is important to understand the topic of chemokines and the scope of their activity in neurological diseases.
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http://dx.doi.org/10.2174/1570159X15666171109161140DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6343204PMC
May 2019

Abnormal mRNA Expression Levels of Telomere-Binding Proteins Represent Biomarkers in Myelodysplastic Syndromes: A Case-Control Study.

Turk J Haematol 2017 Aug 13;34(3):200-206. Epub 2017 Apr 13.

Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Department of Hematology, Jinan, China.

Objective: As evidence was shown that abnormal shortening of telomeres begins to accumulate in myelodysplastic syndrome (MDS) patients, this study was conducted to determine the relationship between the mRNA expression levels of telomere-binding proteins (TRF1/TRF2/TIN2/TPP1/POT1/RAP1) and the risk level in MDS.

Materials And Methods: There were 40 patients with MDS and 40 normal controls in this study. Methods including telomere content assays and quantitative reverse transcription-polymerase chain reaction were used to examine the mRNA levels of TRF1/TRF2/TIN2/TPP1/POT1/RAP1 in patients with MDS.

Results: Compared to the normal group used as a control, the mRNA expression levels of RAP1/POT1/TPP1 of the patients with MDS were decreased, whereas their levels of TRF1/TRF2 and TIN2 were increased. A positive correlation was found between the TRF1, TRF2, and TIN2 mRNA expression levels and the risk level of the International Prognostic Scoring System (IPSS) and the World Health Organization Prognostic Scoring System (WPSS) criteria; however, a negative correlation was found between RAP1/POT1/TPP1 mRNA expression levels and the risk levels of IPSS and WPSS criteria.

Conclusion: Because the reduction of TRF1/TRF2/TIN2 mRNA expression and the increase of RAP1/POT1/TPP1 mRNA expression are closely related to the risk levels of the IPSS and WPSS criteria in MDS, it is thought that these telomere-binding proteins could lead to abnormal telomere length and function, which cause chromosomal abnormalities in MDS. With this evidence, we suggest that those proteins' mRNA expressions could be used as biomarkers for the assessment of the risk degree of MDS patients.
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http://dx.doi.org/10.4274/tjh.2016.0364DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5544038PMC
August 2017

Role of heteroplasmic mutations in the mitochondrial genome and the ID4 gene promoter methylation region in the pathogenesis of chronic aplastic anemia in patients suffering from Kidney yin deficiency.

Chin J Integr Med 2016 Jun 29;22(6):412-9. Epub 2015 Apr 29.

Department of Hematology, Shangdong Province Hospital of Shandong University, Jinan, 250021, China.

Objective: To analyze changes in gene amplification in the mitochondrial genome and in the ID4 gene promoter methylation region in patients with chronic aplastic anemia (CAA) suffering from Kidney (Shen) yin deficiency or Kidney yang deficiency.

Methods: Bone marrow and oral epithelium samples were collected from CAA patients with Kidney yin deficiency or Kidney yang deficiency (20 cases). Bone marrow samples were collected from 20 healthy volunteers. The mitochondrial genome was amplified by polymerase chain reaction (PCR), and PCR products were used for sequencing and analysis.

Results: Higher mutational rates were observed in the ND1-2, ND4-6, and CYTB genes in CAA patients suffering from Kidney yin deficiency. Moreover, the ID4 gene was unmethylated in bone marrow samples from healthy individuals, but was methylated in some CAA patients suffering from Kidney yin deficiency (positive rate, 60%) and Kidney yang deficiency (positive rate, 55%).

Conclusions: These data supported that gene mutations can alter the expression of respiratory chain enzyme complexes in CAA patients, resulting in energy metabolism impairment and promoting the physiological and pathological processes of hematopoietic failure. Functional impairment of the mitochondrial respiration chain induced by gene mutation may be an important reason for hematopoietic failure in patients with CAA. This change is closely related to maternal inheritance and Kidney yin deficiency. Finally, these data supported the assertion that it is easy to treat disease in patients suffering from yang deficiency and difficult to treat disease in patients suffering from yin deficiency.
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http://dx.doi.org/10.1007/s11655-014-1813-7DOI Listing
June 2016

The complexity of DNA double strand break is a crucial factor for activating ATR signaling pathway for G2/M checkpoint regulation regardless of ATM function.

DNA Repair (Amst) 2015 Jan 24;25:72-83. Epub 2014 Nov 24.

School of Radiological Medicine and Protection, Medical College of Soochow University, Suzhou, China. Electronic address:

DNA double strand break (DSB) repair pathway choice following ionizing radiation (IR) is currently an appealing research topic, which is still largely unclear. Our recent paper indicated that the complexity of DSBs is a critical factor that enhances DNA end resection. It has been well accepted that the RPA-coated single strand DNA produced by resection is a signaling structure for ATR activation. Therefore, taking advantage of high linear energy transfer (LET) radiation to effectively produce complex DSBs, we investigated how the complexity of DSB influences the function of ATR pathway on the G2/M checkpoint regulation. Human skin fibroblast cells with or without ATM were irradiated with X rays or heavy ion particles, and dual-parameter flow cytometry was used to quantitatively assess the mitotic entry at early period post radiation by detecting the cells positive for phosphor histone H3. In ATM-deficient cells, ATR pathway played a pivotal role and functioned in a dose- and LET-dependent way to regulate the early G2/M arrest even as low as 0.2Gy for heavy ion radiation, which indicated that ATR pathway could be rapidly activated and functioned in an ATM-independent, but DSB complexity-dependent manner following exposure to IR. Furthermore, ATR pathway also functioned more efficiently in ATM-proficient cells to block G2 to M transition at early period of particle radiation exposure. Accordingly, in contrast to ATM inhibitor, ATR inhibitor had a more effective radiosensitizing effect on survival fraction following heavy ion beams as compared with X ray radiation. Taken together, our results reveal that the complexity of DSBs is a crucial factor for the activation of ATR pathway for G2/M checkpoint regulation, and ATM-dependent end resection is not essential for the activation.
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http://dx.doi.org/10.1016/j.dnarep.2014.11.004DOI Listing
January 2015

Complete sequence analysis of mitochondrial DNA and telomere length in aplastic anemia.

Int J Mol Med 2014 Nov 13;34(5):1309-14. Epub 2014 Aug 13.

Department of Chinese Integrative Medicine, Qingdao Cancer Hospital, Qingdao, Shandong, P.R. China.

The present study was primarily undertaken to examine the hypothesis that mitochondrial DNA (mtDNA) mutations and telomere length may be associated with aplastic anemia (AA). Our study included a single institution analysis of 40 patients presenting with AA first diagnosed at the Affiliated Hospital of Shandong, University of Traditional Chinese Medicine between 2010 and 2013. Bone marrow and oral epithelial samples were collected from patients with AA (n=40) for mtDNA mutation and telomere length determinations. Bone marrow specimens were collected from 40 healthy volunteers as controls for the examination of telomere length. The mitochondrial genome was amplified by polymerase chain reaction (PCR), and the products were used for sequencing and analysis. We detected 146 heteroplasmic mutations in 18 genes from 40 patients with AA, including 39 silent mutations and 28 frameshift mutations. We used the gamma globin gene (HBG) as the control gene in real-time PCR to survey the relative telomere length measurements of the patients with AA and the healthy volunteers. Telomere length was expressed as the relative T/S value. We observed a negative correlation between the mtDNA non-silent mutation and the white blood cell (WBC) count, hemoglobin and platelet count. Of note, there was a positive correlation between the relative T/S value and WBC count, hemoglobin and platelet count, and a negative correlation between the non-silent mutation and the relative T/S value. We conclude that the functional impairment of the mitochondrial respiratory chain induced by mutation and telomere length shortening may play an important role in the process of hematopoietic failure in patients with AA. Additionally, mtDNA mutations and telomere length shortening influenced each other.
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http://dx.doi.org/10.3892/ijmm.2014.1898DOI Listing
November 2014

Arsenite induces premature senescence via p53/p21 pathway as a result of DNA damage in human malignant glioblastoma cells.

BMB Rep 2014 Oct;47(10):575-80

Radiation Risk Reduction Research Program, Research Center for Radiation Protection, National Institute of Radiological Sciences, Chiba 263-8555, Japan.

In this study, we investigate whether arsenite-induced DNA damage leads to p53-dependent premature senescence using human glioblastoma cells with p53-wild type (U87MG-neo) and p53 deficient (U87MG-E6). A dose dependent relationship between arsenite and reduced cell growth is demonstrated, as well as induced γH2AX foci formation in both U87MG-neo and U87MG-E6 cells at low concentrations of arsenite. Senescence was induced by arsenite with senescence-associated β-galactosidase staining. Dimethyl- and trimethyl-lysine 9 of histone H3 (H3DMK9 and H3TMK9) foci formation was accompanied by p21 accumulation only in U87MG-neo but not in U87MG-E6 cells. This suggests that arsenite induces premature senescence as a result of DNA damage with heterochromatin forming through a p53/p21 dependent pathway. p21 and p53 siRNA consistently decreased H3TMK9 foci formation in U87M G-neo but not in U87MG-E6 cells after arsenite treatment. Taken together, arsenite reduces cell growth independently of p53 and induces premature senescence via p53/p21-dependent pathway following DNA damage.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4261516PMC
http://dx.doi.org/10.5483/bmbrep.2014.47.10.254DOI Listing
October 2014

Generation of breast cancer stem cells by steroid hormones in irradiated human mammary cell lines.

PLoS One 2013 16;8(10):e77124. Epub 2013 Oct 16.

Research Center for Radiation Protection, National Institute of Radiological Sciences, Chiba, Japan.

Exposure to ionizing radiation was shown to result in an increased risk of breast cancer. There is strong evidence that steroid hormones influence radiosensitivity and breast cancer risk. Tumors may be initiated by a small subpopulation of cancer stem cells (CSCs). In order to assess whether the modulation of radiation-induced breast cancer risk by steroid hormones could involve CSCs, we measured by flow cytometry the proportion of CSCs in irradiated breast cancer cell lines after progesterone and estrogen treatment. Progesterone stimulated the expansion of the CSC compartment both in progesterone receptor (PR)-positive breast cancer cells and in PR-negative normal cells. In MCF10A normal epithelial PR-negative cells, progesterone-treatment and irradiation triggered cancer and stemness-associated microRNA regulations (such as the downregulation of miR-22 and miR-29c expression), which resulted in increased proportions of radiation-resistant tumor-initiating CSCs.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0077124PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3797732PMC
August 2014

Different effects of carbon ion beams and X-rays on clonogenic survival and DNA repair in human pancreatic cancer stem-like cells.

Radiother Oncol 2012 Nov 24;105(2):258-65. Epub 2012 Sep 24.

Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba, Japan.

Purpose: The effects of a carbon ion beam and X-rays on human pancreatic cancer stem-like cells were examined from the point of view of clonogenic survival and DNA repair.

Materials And Methods: Human pancreatic cancer stem-like cells were treated with and without carbon ion and X-ray irradiation, and then colony, spheroid and tumor formation assays as well as γH2AX foci formation assay were performed.

Results: The relative biological effectiveness (RBE) values of a carbon ion beam relative to X-ray for the MIA PaCa-2 and BxPc-3 cells at the D10 values were 1.85-2.10. The ability for colony, spheroid formation, and tumorigenicity from cancer stem-like CD44(+)/CD24(+) cells is significantly higher than that from non-cancer stem-like CD44(-)/CD24(-)cells. FACS data showed that CD44(+)/CD24(+) cells were more highly enriched after X-rays compared to carbon ion irradiation at isoeffective doses. The RBE values for the carbon ion beam relative to X-ray at the D10 levels for CD44(+)/CD24(+) cells were 2.0-2.19. The number of γH2AX foci in CD44(-)/CD24(-) cells was higher than that of CD44(+)/CD24(+) cells after irradiation with either X-ray or carbon ion beam. The number of γH2AX foci in CD44(+)/CD24(+) cells was almost the same in the early time, but it persists significantly longer in carbon ion beam irradiated cells compared to X-rays.

Conclusions: Carbon ion beam has superior potential to kill pancreatic cancer stem cell-like cells, and prolonged induction of DNA damage might be one of the pivotal mechanisms of its high radiobiological effects compared to X-rays.
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http://dx.doi.org/10.1016/j.radonc.2012.08.009DOI Listing
November 2012

Berberine suppresses amyloid-beta-induced inflammatory response in microglia by inhibiting nuclear factor-kappaB and mitogen-activated protein kinase signalling pathways.

J Pharm Pharmacol 2012 Oct 9;64(10):1510-21. Epub 2012 May 9.

Institute of Medical Genetics and Key Laboratory for Experimental Teratology of the Ministry of Education, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China.

Objectives: The neuroinflammation induced by amyloid-beta peptide (Aβ) is one of the key events in Alzheimer's disease (AD) progress in which microglia are the main cells involved. Berberine, one of the major constituents of Chinese herb Rhizoma coptidis, is known for its anti-inflammatory, anti-oxidative and anti-microbial activity. In this study, we examined the effects and possible underlying mechanisms of berberine in Aβ-induced neuroinflammation using murine primary microglia cells and cultured BV2 microglia cells.

Methods: The effects of berberine on Aβ-stimulated inflammatory factor expression and secretion were examined using RT-PCR and ELISA analysis. The signal pathways involved in berberine's effects were also investigated using Western blot and immunofluorescence analysis.

Results: In primary microglial and BV2 cells, berberine treatment significantly inhibited Aβ-stimulated production of interleukin-6 and monocyte chemotactic protein-1. Berberine treatment down-regulated the expression of cyclo-oxygenase-2 and induced nitric oxide synthase in these cells. Moreover, berberine strongly inhibited the nuclear factor-kappaB (NF-κB) activation, presumably through blocking the phosphoinositide 3-kinase/protein kinase B and mitogen-activated protein kinase signalling pathways.

Conclusions: Our data indicated berberine is a potent suppressor of neuroflammation, presumably through inhibition of NF-κB activation, and suggested berberine has therapeutic potential for the treatment of neuroinflammation that is involved in neurological diseases such as AD.
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http://dx.doi.org/10.1111/j.2042-7158.2012.01529.xDOI Listing
October 2012
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