Publications by authors named "Jumei Liu"

27 Publications

  • Page 1 of 1

Noninvasive evaluation of tumor immune microenvironment in patients with clear cell renal cell carcinoma using metabolic parameter from preoperative 2-[F]FDG PET/CT.

Eur J Nucl Med Mol Imaging 2021 May 12. Epub 2021 May 12.

Department of Nuclear Medicine, Peking University First Hospital, Beijing, 100034, China.

Purpose: Nowadays, it is necessary to explore effective biomarkers associated with tumor immune microenvironment (TIME) noninvasively. Here, we investigated whether the metabolic parameter from preoperative 2-[F]FDG PET/CT could provide information related to TIME in patients with clear cell renal cell carcinoma (ccRCC).

Methods: Ninety patients with newly diagnosed ccRCC who underwent 2-[F]FDG PET/CT prior to surgery were retrospectively reviewed. The immunological features included tumor-infiltrating lymphocytes (TILs) density, programmed death-ligand 1 (PD-L1) expression, and tumor immune microenvironment types (TIMTs). TIMTs were classified as TIMT I (positive PD-L1 and high TILs), TIMT II (negative PD-L1 and low TILs), TIMT III (positive PD-L1 and low TILs), and TIMT IV (negative PD-L1 and high TILs). The relationship between maximum standardized uptake value (SUVmax) in the primary lesion from 2-[F]FDG PET/CT and immunological features was analyzed. Cox proportional hazards analyses were performed to identify the prognostic factors for disease-free survival (DFS) after nephrectomy.

Results: Tumors with high TILs infiltration showed remarkable correlation with elevated SUVmax and aggressive clinicopathological characteristics, such as high World Health Organization/International Society of Urological Pathology (WHO/ISUP) grade. PD-L1 expression on tumor cells was positively associated with WHO/ISUP grade and negatively correlated with body mass index (BMI). However, no correlation was observed between SUVmax and PD-L1 expression, regardless of its spatial tissue distribution. SUVmax of TIMT I and IV was higher than that of TIMT II, but there was remarkable difference merely between TIMT II and IV. In multivariate analysis, SUVmax (P = 0.022, HR 3.120, 95% CI 1.175-8.284) and WHO/ISUP grade (P = 0.046, HR 2.613, 95% CI 1.017-6.710) were the significant prognostic factors for DFS. Six cases (16.2%) with normal SUVmax showed disease progression, while 25 cases (71.4%) with elevated SUVmax experienced disease progression. Conversely, the immunological features held no prognostic value.

Conclusions: Our findings demonstrated that 2-[F]FDG PET/CT could provide metabolic information of TIME for ccRCC patients and develop image-guided therapeutic strategies accordingly. Patients with elevated preoperative SUVmax should be seriously considered, and perioperative immunotherapy might be beneficial for them.
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http://dx.doi.org/10.1007/s00259-021-05399-9DOI Listing
May 2021

Elevated Atmospheric CO and Nitrogen Fertilization Affect the Abundance and Community Structure of Rice Root-Associated Nitrogen-Fixing Bacteria.

Front Microbiol 2021 21;12:628108. Epub 2021 Apr 21.

Ministry of Education Key Laboratory of Ecology and Resource Use of the Mongolian Plateau and Inner Mongolia Key Laboratory of Grassland Ecology, School of Ecology and Environment, Inner Mongolia University, Hohhot, China.

Elevated atmospheric CO (eCO) results in plant growth and N limitation, yet how root-associated nitrogen-fixing bacterial communities respond to increasing atmospheric CO and nitrogen fertilization (eN) during the growth stages of rice is unclear. Using the gene as a molecular marker, we studied the combined effect of eCO and eN on the diazotrophic community and abundance at two growth stages in rice (tillering, TI and heading, HI). Quantitative polymerase chain reaction (qPCR) showed that eN had no obvious effect on abundance in rice roots under either ambient CO (aCO) or eCO treatment at the TI stage; in contrast, at the HI, copy numbers were increased under eCO and decreased under aCO. For rhizosphere soils, eN significantly reduced the abundance of under both aCO and eCO treatment at the HI stage. Elevated CO significantly increased the abundance in rice roots and rhizosphere soils with nitrogen fertilization, but had no obvious effect without N addition at the HI stage. There was a significant interaction [CO × N fertilization] effect on abundance in root zone at the HI stage. In addition, the copy numbers in rice roots were significantly higher at the HI stage than at the TI stage. Sequencing analysis indicated that the root-associated diazotrophic community structure tended to cluster according to the nitrogen fertilization treatment and that were the dominant diazotrophs in all root samples at the HI stage. Additionally, nitrogen fertilization significantly increased the relative abundance of () under eCO treatment, but significantly decreased the relative abundance of () under aCO treatment. Overall, the combined effect of eN and eCO stimulates root-associated diazotrophic methane-oxidizing bacteria while inhibits heterotrophic diazotrophs.
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http://dx.doi.org/10.3389/fmicb.2021.628108DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8103900PMC
April 2021

Mutational characteristics of gastrointestinal stromal tumors: A single-center analysis of 302 patients.

Oncol Lett 2021 Feb 4;21(2):174. Epub 2021 Jan 4.

Department of Pathology, Peking University First Hospital, Beijing 100034, P.R. China.

Gastrointestinal stromal tumors (GISTs) represent a spectrum of tumors characterized by variable behaviors and activating mutations in KIT proto-oncogene, receptor tyrosine kinase () or platelet derived growth factor receptor α () genes. However, whether genotype analysis should be regarded as a prognostic indicator remains unclear. In the present study, clinicopathological data and the mutation phenotypes of and genes were assessed in a series of 302 patients with GISTs at a single center. Univariate and multivariate Cox regression analyses were performed to identify the clinicopathological and mutational factors associated with relapse-free survival (RFS) in patients who had undergone complete primary GIST resection. and mutations were identified in 233 (77.2%) and 30 (9.9%) cases, respectively. The following clinicopathological parameters were significantly associated with a shorter RFS: Male, non-gastric tumor origin, larger tumor size (>5 cm), high mitotic activity (>5/50 high-power fields), necrosis and epithelioid morphology. Tumors at non-gastric sites, with high National Institutes of Health risk classification, high World Health Organization (WHO) grade and deletion involving codons 557/558/559 exhibited a significantly higher risk of progression. In the Cox regression model, deletion involving codons 557/558/559, non-gastric origin and high WHO grade were independent indicators of RFS. The adverse prognosis associated with deletions involving codons 557/558/559 was also observed for gastric GISTs. Conversely, spindle morphology, exon 11 substitution and exon 18 mutation were associated with a longer RFS and lower rate of relapse. Furthermore, the coexistence of exon 11 deletion and exon 13 duplication was observed in one tumor, with adverse prognostic features. Heterogeneity affecting morphology, immunostaining and genotype was identified in 4 cases. In addition, the presence of succinate dehydrogenase-deficient GIST was found in 5 cases (3.6%). In conclusion, the tumor genotype with regard to and mutations exhibited prognostic significance for the risk of GIST progression and may be helpful for the optimization of tailored adjuvant therapy.
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http://dx.doi.org/10.3892/ol.2021.12435DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7798044PMC
February 2021

Molecular cloning, expression and characterization of aspartyl protease inhibitor from Ancylostoma ceylanicum.

Vet Parasitol Reg Stud Reports 2020 12 10;22:100464. Epub 2020 Sep 10.

Guangdong Provincial Zoonosis Prevention and Control Key Laboratory, College of Veterinary Medicine, South China Agricultural University, Guangzhou 510542, China. Electronic address:

Aspartyl protease inhibitors (APIs) from parasitic intestinal nematodes are highly immunogenic and have been suggested as potential vaccine antigens. Ac-API-1 from Ancylostoma caninum showed strong immunogenicity and its polyclonal antibodies could specifically recognize the excretory/secretory products of adult worms. However, little is known about molecular characteristics and biological function of API from Ancylostoma ceylanicum (Ace-API). In this study, the Ace-API mature peptide coding sequence was cloned and expressed, and molecular characteristics of its full length sequence were analyzed. Ace-API cDNA was 684 bp in length, which encoded 228 amino acids. The similarity of the Ace-API amino acid sequence to Ac-API-1 and Adu-API-1 was 96.93% and 96.49%, respectively, and they clustered together in the phylogenetic tree. Escheria coli-expressed recombinant protein was mainly soluble in the supernatant of bacterial cell lysate. Western blot showed that Ace-API protein had good reactivity to the serum of infected dogs. Pepsin inhibition assay revealed that the recombinant protein had inhibitory activity on pepsin. Immunofluorescence results demonstrated that Ace-API was mainly localized to the epidermis, excretory glands, and pseudocoelomic fluid of the adult. Using the quantitative real-time PCR, the expression of Ace-api mRNA in adults was significantly higher than that in the third stage (L3) larvae. Together, these data indicate that Ace-API is secreted extracellularly by the parasite, and might play a role in protecting the parasite against the proteolytic digestion by the host proteases, which stimulate further studies to explore this protein as a potential hookworm vaccine candidate.
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http://dx.doi.org/10.1016/j.vprsr.2020.100464DOI Listing
December 2020

IgG4 immunohistochemistry in Riedel's thyroiditis and the recommended criteria for diagnosis: A case series and literature review.

Clin Endocrinol (Oxf) 2021 May 21;94(5):851-857. Epub 2020 Dec 21.

Department of Endocrinology, Peking University First Hospital, Beijing, China.

Objective: Riedel's thyroiditis (RT) is a very rare chronic fibrosing thyroiditis that is often associated with multifocal fibrosclerosis. Although the relationship of RT and IgG4-related disease (IgG4-RD) has been suggested, the expression of IgG and IgG4 in thyroid tissues of patients with RT has seldom been studied.

Design: A case series and literature review.

Patients And Measurements: We searched our hospital's pathology database and identified five cases of RT between 2000 and 2019. The expression levels of IgG4 and IgG in thyroid tissues were detected by immunohistochemistry. We also performed a literature search of the electronic databases PubMed/MEDLINE, Web of Science and China National Knowledge Internet (CNKI). Eight papers were included in this study.

Results: According to immunohistochemistry, the numbers of IgG4+ plasma cells per high-power field (HPF) of the five RT patients at our hospital were 80, 8, 50, 10 and 22, and the respective IgG4+/IgG+ ratios were 76%, 80%, 43%, 19% and 28%. In the literature, 15 RT patients with confirmed IgG4 and IgG immunohistochemical findings were identified. Only seven of them fulfilled the IgG4-RD diagnostic criteria in terms of immunohistochemistry (IgG4+ > 10/HPF, IgG4+/IgG+ > 40%). In order to ensure that most RT cases can meet the IgG4 immunohistochemical criteria, an organ-specific cut-off value (≥10 IgG4+ plasma cells/HPF and ≥ an IgG4+/IgG ratio of 20%) was finally selected in our study.

Conclusion: Our findings of IgG4 expression in patients with RT suggest that a cut-off of 10 IgG4+ plasma cells/HPF and an IgG4+/IgG ratio of 20% are more suitable diagnostic criteria for RT in IgG4-RD.
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http://dx.doi.org/10.1111/cen.14390DOI Listing
May 2021

Plasma miRNA profiles associated with stable warfarin dosage in Chinese patients.

PeerJ 2020 13;8:e9995. Epub 2020 Oct 13.

School of Medicine, Xiamen University, Xiamen, China.

Background: We used bioinformatic analysis and quantitative reverse transcription polymerase chain reaction (RT-qPCR) assays to investigate the association between plasma microRNAs (miRNAs) and stable warfarin dosage in a Chinese Han population.

Methods: Bioinformatics analysis was used to screen out potential warfarin dose-associated miRNAs. Three plasma miRNAs were validated in 99 samples by RT-qPCR. Kruskal-Wallis test and multivariate logistic regression were used to compare differences in plasma miRNAs expression levels between three warfarin dosage groups.

Results: There were significant between-group differences among the three dose groups for hsa-miR-133b expression ( = 0.005), but we observed an "n-shaped" dose-dependent curve rather than a linear relationship. Expression levels of hsa-miR-24-3p ( = 0.475) and hsa-miR-1276 ( = 0.558) were not significantly different in the multivariate logistic regression.

Conclusion: miRNAs have received extensive attention as ideal biomarkers and possible therapeutic targets for various diseases. However, they are not yet widely used in precision medicine. Our results indicate that hsa-miR-133b may be a possible reference factor for the warfarin dosage algorithm. These findings emphasize the importance of a comprehensive evaluation of complex relationships in warfarin dose prediction models and provide new avenues for future pharmacogenomics studies.
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http://dx.doi.org/10.7717/peerj.9995DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7566751PMC
October 2020

MicroRNA miR-155-5p knockdown attenuates Angiostrongylus cantonensis-induced eosinophilic meningitis by downregulating MMP9 and TSLP proteins.

Int J Parasitol 2021 Jan 20;51(1):13-22. Epub 2020 Sep 20.

Department of Pathogen Biology and Experimental Teaching Center of Preventive Medicine, Guangdong Provincial Key Laboratory of Tropical Disease, School of Public Health, Southern Medical University, Guangzhou 510515, PR China. Electronic address:

Angiostrongylus cantonensis infection is a major cause of eosinophilic meningitis (EM). Severe cases or cases that involve infants and children present poor prognoses. MicroRNAs (miRNAs), which are important regulators of gene expression in many biological processes, were recently found to be regulators of the host response to infection by parasites; however, their roles in brain inflammation caused by A. cantonensis are still unclear. The current study confirmed that miR-155-5p peaked at 21 days after A. cantonensis infection, and its expression was positively correlated with the concentration of excretory and secretory products (ESPs). We found that miR-155-5p knockdown lentivirus successfully ameliorated brain injury and downregulated the expression of major basic protein (MBP) in vivo, and the number of eosinophils in CSF (and the percentage of eosinophils in peripheral blood were also decreased in the miR-155-5p knockdown group. Moreover, the expression of several eosinophilic inflammation cytokines such as CCL6/C10, ICAM-1, and MMP9, declined after the miR-155-5p knockdown. SOCS1 protein, which is an important negative regulator of inflammation activation, was identified as a direct miR-155-5p target. We further detected the effect of miR-155-5p knockdown on phosphorylated-STAT3 and phosphorylated-p65 proteins, which were found to be negatively regulated by SOCS1 and play an important role in regulating the inflammatory response. We found that miR-155-5p knockdown decreased the activity of p-STAT3 and p-p65, thereby leading to lower expression of MMP9 and TSLP proteins, which were closely related to the chemotaxis and infiltration of eosinophils. Interestingly, the inhibition of p-STAT3 or p-p65 was found to induce the downregulation of miR-155-5p in an opposite manner. These observations suggest that a positive feedback loop was formed between miR-155-5p, STAT3, and NF-κB in A. cantonensis infection and that miR-155-5p inhibition might provide a novel strategy to attenuate eosinophilic meningitis.
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http://dx.doi.org/10.1016/j.ijpara.2020.07.013DOI Listing
January 2021

Pyrimethamine Elicits Antitumor Effects on Prostate Cancer by Inhibiting the p38-NF-κB Pathway.

Front Pharmacol 2020 25;11:758. Epub 2020 May 25.

Department of Pathogen Biology and Experimental Teaching Center of Preventive Medicine, Guangdong Provincial Key Laboratory of Tropical Disease, School of Public Health, Southern Medical University, Guangzhou, China.

Since incurable castration-resistant prostate cancer (CRPC) inevitably develops following treatment with androgen deprivation therapy, there is an urgent need to devise new therapeutic strategies to treat this cancer. Pyrimethamine, an FDA-approved antimalarial drug, is known to exert an antitumor activity in various types of human cancer cells. However, whether pyrimethamine can inhibit prostate cancer is not well established. Hence, the present study aimed to characterize the mechanism of action of pyrimethamine on prostate cancer. We investigated the potential effect of pyrimethamine on cell proliferation, cell cycle, and apoptosis in metastatic DU145 and PC3 prostate cancer cells. We found that pyrimethamine inhibited cell proliferation, induced cell cycle arrest in the S phase, and promoted cell apoptosis of prostate cells ; it also suppressed tumor growth in xenograft models. In addition, we observed that pyrimethamine suppressed prostate cancer growth by inhibiting the p38-NF-κB axis and . Thus, this study demonstrates that pyrimethamine is a novel p38 inhibitor that can exert antiproliferative and proapoptotic effects in prostate cancer by affecting cell cycle and intrinsic apoptotic signaling, thereby providing a novel strategy for using pyrimethamine in CRPC treatment.
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http://dx.doi.org/10.3389/fphar.2020.00758DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7261869PMC
May 2020

Diversity of active root-associated methanotrophs of three emergent plants in a eutrophic wetland in northern China.

AMB Express 2020 Mar 14;10(1):48. Epub 2020 Mar 14.

Ministry of Education Key Laboratory of Ecology and Resource Use of the Mongolian Plateau & Inner Mongolia Key Laboratory of Grassland Ecology, School of Ecology and Environment, Inner Mongolia University, 235 West University Street, Hohhot, 010021, China.

Root-associated aerobic methanotrophs play an important role in regulating methane emissions from the wetlands. However, the influences of the plant genotype on root-associated methanotrophic structures, especially on active flora, remain poorly understood. Transcription of the pmoA gene, encoding particulate methane monooxygenase in methanotrophs, was analyzed by reverse transcription PCR (RT-PCR) of mRNA isolated from root samples of three emergent macrophytes, including Phragmites australis, Typha angustifolia, and Schoenoplectus triqueter (syn. Scirpus triqueter L.) from a eutrophic wetland. High-throughput sequencing of pmoA based on DNA and cDNA was used to analyze the methanotrophic community. Sequencing of cDNA pmoA amplicons confirmed that the structure of active methanotrophic was not always consistent with DNA. A type I methanotroph, Methylomonas, was the most active group in P. australis, whereas Methylocystis, a type II methanotroph, was the dominant group in S. triqueter. In T. angustifolia, these two types of methanotroph existed in similar proportions. However, at the DNA level, Methylomonas was predominant in the roots of all three plants. In addition, vegetation type could have a profound impact on root-associated methanotrophic community at both DNA and cDNA levels. These results indicate that members of the genera Methylomonas (type I) and Methylocystis (type II) can significantly contribute to aerobic methane oxidation in a eutrophic wetland.
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http://dx.doi.org/10.1186/s13568-020-00984-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7070141PMC
March 2020

Mitochondrial Genome Sequence of Echinostoma revolutum from Red-Crowned Crane (Grus japonensis).

Korean J Parasitol 2020 Feb 29;58(1):73-79. Epub 2020 Feb 29.

Guangdong Provincial Zoonosis Prevention and Control Key Laboratory, College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, People's Republic of China.

Echinostoma revolutum is a zoonotic food-borne intestinal trematode that can cause intestinal bleeding, enteritis, and diarrhea in human and birds. To identify a suspected E. revolutum trematode from a red-crowned crane (Grus japonensis) and to reveal the genetic characteristics of its mitochondrial (mt) genome, the internal transcribed spacer (ITS) and complete mt genome sequence of this trematode were amplified. The results identified the trematode as E. revolutum. Its entire mt genome sequence was 15,714 bp in length, including 12 protein-coding genes, 22 transfer RNA genes, 2 ribosomal RNA genes and one non-coding region (NCR), with 61.73% A+T base content and a significant AT preference. The length of the 22 tRNA genes ranged from 59 bp to 70 bp, and their secondary structure showed the typical cloverleaf and D-loop structure. The length of the large subunit of rRNA (rrnL) and the small subunit of rRNA (rrnS) gene was 1,011 bp and 742 bp, respectively. Phylogenetic trees showed that E. revolutum and E. miyagawai clustered together, belonging to Echinostomatidae with Hypoderaeum conoideum. This study may enrich the mitochondrial gene database of Echinostoma trematodes and provide valuable data for studying the molecular identification and phylogeny of some digenean trematodes.
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http://dx.doi.org/10.3347/kjp.2020.58.1.73DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7066449PMC
February 2020

Anticoagulation regimens during pregnancy in patients with mechanical heart valves: a protocol for a systematic review and network meta-analysis.

BMJ Open 2020 02 10;10(2):e033917. Epub 2020 Feb 10.

School of Public Health, Xiamen University, Xiamen, China

Introduction: Pregnancy in patients with mechanical heart valves (MHVs) is associated with high maternal complications and fetal complications.Anticoagulation treatments serve to decrease their venous clotting risk. Although some anticoagulation regimens have been used for patients during pregnancy with MHVs, no one is definitively superior among different regimens in recent studies. For a better understanding of the clinical treatment which anticoagulation regimen is more effective and safer during the pregnancy in patients with MHVs, a Bayesian network meta-analysis is necessary.

Methods And Analysis: This protocol has been reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols. Related studies until April 2019 will be searched in the following databases: PubMed, Embase,SinoMed and the using the OVID interface to search for evidence-based medicine reviews. A clinical trial registry (www.ClinicalTrials.gov) was also searched for unpublished trials. Both experimental studies (randomised clinical trials) and observational studies (cohort studies, case-control studies and case series studies) will be included in this study. Quality assessment will be conducted using Cochrane Collaboration's tool or Newcastle-Ottawa Scale based on their study designs. The primary outcomes of interest will be the frequencies of serious maternal and fetal events. The additional outcomes of interest will be adverse maternal events, mode of delivery and adverse fetal events. Pairwise and network meta-analysis will be conducted using R (V.3.4.4, R Foundation for Statistical Computing, Vienna, Austria) and Stata (V.14, StataCorp). The ranking probabilities will be estimated at each possible rank for each anticoagulation regimen using the surface under the cumulative ranking curve. Statistical inconsistency assessment, subgroup analysis, sensitivity analysis and publication bias assessment will be performed.

Ethics And Dissemination: Either ethics approval or patient consent is not necessary, because this study will be based on literature. The results of this study will be published in a peer-reviewed journal.

Prospero Registration Number: CRD42019130659.
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http://dx.doi.org/10.1136/bmjopen-2019-033917DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7045236PMC
February 2020

Identification and localization of hookworm platelet inhibitor in Ancylostoma ceylanicum.

Infect Genet Evol 2020 01 2;77:104102. Epub 2019 Nov 2.

Guangdong Provincial Zoonosis Prevention and Control Key Laboratory, College of Veterinary Medicine, South China Agricultural University, Guangzhou 510542, China. Electronic address:

Ancylostoma ceylanicum is a zoonotic hookworm, which mainly causes iron deficiency anemia (IDA) in humans and animals. Hookworm platelet inhibitor (HPI) has been isolated from adult Ancylostoma caninum and linked to the pathogenesis of hookworm associated intestinal hemorrhage and IDA. However, there is no available data about HPI from A. ceylanicum. To study the molecular characteristics of A. ceylanicum HPI (Ace-HPI), its corresponding cDNA was amplified from adult A. ceylanicum mRNA using the primers designed based on the Ac-HPI gene sequence, and its sequence homology and phylogenetic relationship were analyzed. The differential expression of Ace-hpi mRNA in the adult and third larval (L3) stages was compared using the quantitative real-time PCR. Ace-HPI reactivity and tissue localization were studied by Western blot and immunofluorescence, respectively. Platelet aggregation activity was monitored in a 96-well microplate reader. The results showed that the Ace-HPI encoding gene was 603 bp in length. Ace-HPI showed 91% homology to Ac-HPI, was closely related to Ac-ASP3, and belonged to the CAP superfamily. Ace-hpi transcripts were most abundant in the adult stage, followed by serum-stimulated infective larvae (ssL3), and finally in L3 stage, with a significant difference. Escherichia coli-expressed recombinant protein had good reactivity with the positive serum of A. ceylanicum-infected dogs. Immunolocalization indicated that Ace-HPI was located in the esophagus and cephalic glands of the adult. As well as, recombinant Ace-HPI inhibited the platelet aggregation in-vitro. HPI overexpression, anatomical location in adults, antigenicity and its in-vitro activity indicate its possible role in adult worm blood-feeding and as a valuable target for hookworm vaccine and drug development.
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http://dx.doi.org/10.1016/j.meegid.2019.104102DOI Listing
January 2020

Applications of Catalytic Hairpin Assembly Reaction in Biosensing.

Small 2019 10 16;15(42):e1902989. Epub 2019 Sep 16.

Department of Clinical Laboratory, Women and Children's Hospital, School of Medicine, Xiamen University, Xiamen, 361003, P. R. China.

Nucleic acids are considered as perfect programmable materials for cascade signal amplification and not merely as genetic information carriers. Among them, catalytic hairpin assembly (CHA), an enzyme-free, high-efficiency, and isothermal amplification method, is a typical example. A typical CHA reaction is initiated by single-stranded analytes, and substrate hairpins are successively opened, resulting in thermodynamically stable duplexes. CHA circuits, which were first proposed in 2008, present dozens of systems today. Through in-depth research on mechanisms, the CHA circuits have been continuously enriched with diverse reaction systems and improved analytical performance. After a short time, the CHA reaction can realize exponential amplification under isothermal conditions. Under certain conditions, the CHA reaction can even achieve 600 000-fold signal amplification. Owing to its promising versatility, CHA is able to be applied for analysis of various markers in vitro and in living cells. Also, CHA is integrated with nanomaterials and other molecular biotechnologies to produce diverse readouts. Herein, the varied CHA mechanisms, hairpin designs, and reaction conditions are introduced in detail. Additionally, biosensors based on CHA are presented. Finally, challenges and the outlook of CHA development are considered.
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http://dx.doi.org/10.1002/smll.201902989DOI Listing
October 2019

Prognostic impact of diffuse large B-cell lymphoma with extra copies of MYC, BCL2 and/or BCL6: comparison with double/triple hit lymphoma and double expressor lymphoma.

Diagn Pathol 2019 Jul 17;14(1):81. Epub 2019 Jul 17.

Department of Pathology, Peking University First Hospital, 8 Xishiku Street, Xicheng District, Beijing, 100034, China.

Background: The poor outcome of high-grade B-cell lymphoma, with rearrangements of MYC, BCL2 and/or BCL6, also known as double-hit lymphoma or triple-hit lymphoma (DHL or THL), has been well documented, while the clinical significance of extra copies of MYC, BCL2 or BCL6 are still less well known.

Methods: In total, 130 cases of diffuse large B-cell lymphoma, not otherwise specified (DLBCL-NOS) were included in our study. Fluorescence in situ hybridization and immunohistochemistry were performed in all cases to evaluate the genetic status and protein expression levels of MYC, BCL2 and BCL6.

Results: Among the 130 cases of DLBCL, the prevalence rates of extra copies of MYC, BCL2 and BCL6 were 10.8, 20.0 and 14.6%, respectively, and the corresponding rates of gene rearrangement were 10.0, 14.6 and 16.9%, respectively. In total, 7.7% (10/130) of patients were DHL/THL; 9.2% (12/130) of patients were DLBCL with MYC and BCL2 and/or BCL6 gene abnormalities including rearrangements or extra copies, while excluded DHL/THL. The positive protein expression rates of MYC, BCL2 and BCL6 were 46.9% (61), 75.4% (98) and 70.0% (91), respectively. Among the 51 cases with MYC/BCL2 co-expression, 14 cases showed concurrence of MYC, BCL2 and/or BCL6 genetic abnormalities, and the remaining 37 cases were classified as double-expressor lymphoma (DEL). MYC and BCL2 rearrangement and BCL2 extra copies were all associated with upregulated protein expression. Cases with concurrence of MYC, BCL2 and/or BCL6 genetic abnormalities were both associated with MYC/BCL2 co-expression. Patients with concurrence of MYC, BCL2 and/or BCL6 genetic abnormalities excluded DHL/THL had shorter OS (P < 0.001) than patients with DLBCL with no genetic change, and showed no statistical different with patients with DHL/THL (P = 0.419). Extra copies of MYC was independent prognostic factors for DLBCL.

Conclusions: Patients with MYC and BCL2 and/or BCL6 gene extra copies might show a trend towards poor prognosis, and the detection of extra copies of MYC, BCL2 and BCL6 might deserve more attention.
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http://dx.doi.org/10.1186/s13000-019-0856-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6637540PMC
July 2019

Comparison of PD-L1 detection assays and corresponding significance in evaluation of diffuse large B-cell lymphoma.

Cancer Med 2019 07 31;8(8):3831-3845. Epub 2019 May 31.

Department of Pathology, Peking University First Hospital, Beijing, China.

The expression of programmed cell death ligand 1 (PD-L1) is a biomarker for immunotherapy, but approved detection method is absent in diffuse large B-cell lymphoma (DLBCL). Here, we performed three methods including immunohistochemistry (IHC) (clone SP263 and SP142), RNAscope, and fluorescence in situ hybridization (FISH) to evaluate PD-L1 status on a cohort of DLBCL including 94 of DLBCL-NOS, 25 of primary mediastinal large B-cell lymphoma (PMBCL) and 7 of double-hit lymphoma (DHL). SP263 with 25% for immune cell (IC) or combined cell and SP142 with 10% for tumor cell (TC), 20% for both of IC and combined cell were proved to have corresponding survival prognostic. Combined showed comparable prognostic value with TC and IC . SP263 and SP142 showed strong concordance (k = 0.788) with combined rates of 33.3% (42/126) and 34.9% (44/126), respectively. In DLBCL-NOS, TC by SP263 preferred to non-GCB and immunoblastic variant DLBCL-NOS (P = 0.029 and P = 0.004). Combined (SP263 and SP142) were associated with more than one extranodal site involved (P = 0.006, P = 0.042), higher ECOG PS scores (P = 0.001, P < 0.001), high IPI risk (P = 0.012, P = 0.005), and poor treatment response (P = 0.095, P = 0.002). IC by SP263 and SP142 were both independent risk factors (P = 0.027, P = 0.037). 9p24.1 locus amplification and gain were identified in 4.3% and 7.6% DLBCL-NOS and indicated shorter overall survival (P = 0.004). Positive rate of PD-L1 by RNAscope was 36.5%, while no clinical significance shown. PD-L1 positive rates were all higher in PMBCL and DHL than in DLBCL-NOS by SP263, SP142, RNAscope, and FISH (P = 0.001, P < 0.001, P = 0.005 and P < 0.001, respectively). In conclusion, combined PD-L1 expression by IHC was potentially reliable and convenient as a predicting biomarker. SP263 staining was easier to evaluate and recognized more PD-L1-stained cells, but SP142 presented a better prognostic indicator. FISH and RNAscope could be used as supplementary assays. PMBCL itself was a sensitive cohort for immunotherapy.
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http://dx.doi.org/10.1002/cam4.2316DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6639200PMC
July 2019

JAK3/STAT3 oncogenic pathway and PRDM1 expression stratify clinicopathologic features of extranodal NK/T‑cell lymphoma, nasal type.

Oncol Rep 2019 Jun 12;41(6):3219-3232. Epub 2019 Apr 12.

Department of Pathology, Peking University First Hospital, Beijing 100034, P.R. China.

The inactivation of tumor suppressor gene positive regulatory domain containing I (PRDM1) and activation of signal transducer and activator of transcription 3 (STAT3) have been detected in the majority of extranodal NK/T‑cell lymphoma, nasal type (EN‑NK/T‑NT) cases. In the present study, their association with and effects on the clinicopathologic features of EN‑NK/T‑NT are described. PRDM1 was revealed to be expressed in 19 out of 58 patients (32.8%) with EN‑NK/T‑NT, and phosphorylated STAT3 was overexpressed in 42 out of 58 (72.4%). Oncogenic pathways were investigated by NanoString encounter technology in 5 PRDM1(+) and 5 PRDM1(‑) EN‑NK/T‑NT specimens. Multiple oncogenic pathways involved in cell apoptosis, cellcycle (CC) and angiogenesis were discriminately activated in EN‑NK/T‑NT cases, and in PRDM1(+) cases in particular. The sustained activation of the Janus kinase 3 (JAK)/STAT3 pathway was more pronounced. In addition, missense mutations in the SRC homology 2 domain of STAT3 were detected in 7 out of 37 EN‑NK/T‑NT cases (18.92%), and the acquired mutation was related to the activation of the JAK3/STAT3 pathway. The downregulation of PRDM1 and upregulation of phospho‑STAT3 (Tyr705) were associated with angiocentric infiltration of EN‑NK/T‑NT (P=0.039). Notably, the prognosis of patients in the PRDM1(+)/STAT3 [mutated (mut‑)] group was considerably improved than that of patients in the STAT3(mut+)/PRDM(‑) group (P=0.037). In addition, the inhibition of NK/T cell lymphoma cell lines by Stattic and tofacitinib could suppress cell proliferation by inducing cell apoptosis or arresting the CC. The present results revealed that the JAK3/STAT3 oncogenic pathway and PRDM1 expression could stratify clinicopathologic features of EN‑NK/T‑NT. The inhibition of the JAK3/STAT3 pathway may serve as a treatment option for EN‑NK/T‑NT.
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http://dx.doi.org/10.3892/or.2019.7112DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6488994PMC
June 2019

Establishment of a Tm-shift Method for Detection of Cat-Derived Hookworms.

Korean J Parasitol 2019 Feb 26;57(1):9-15. Epub 2019 Feb 26.

Guangdong Provincial Zoonosis Prevention and Control Key Laboratory, College of Veterinary Medicine, South China Agricultural University, Guangzhou 510542, P. R. China.

Melting temperature shift (Tm-shift) is a new detection method that analyze the melting curve on real-time PCR thermocycler using SYBR Green I fluorescent dye. To establish a Tm-shift method for the detection of Ancylostoma ceylanicum and A. tubaeforme in cats, specific primers, with GC tail of unequal length attached to their 5 ́ end, were designed based on 2 SNP loci (ITS101 and ITS296) of the internal transcribed spacer 1 (ITS1) sequences. The standard curve of Tm-shift was established using the standard plasmids of A. ceylanicum (AceP) and A. tubaeforme (AtuP). The Tm-shift method stability, sensitivity, and accuracy were tested with reference to the standard curve, and clinical fecal samples were also examined. The results demonstrated that the 2 sets of primers based on the 2 SNPs could accurately distinguish between A. ceylanicum and A. tubaeforme. The coefficient of variation (CV) of Tm-values of AceP and AtuP was 0.07% and 0.06% in ITS101 and was 0.06% and 0.08% in ITS296, respectively. The minimum detectable DNA concentration was 5.22×10-6 and 5.28×10-6 ng/μl samples of AceP and AtuP, respectively. The accuracy of Tm-shift method reached 100% based on examination of 10 hookworm DNA samples with known species. In the clinical detection of hookworm in 69 stray cat fecal sample, the Tm-shift detection results were consistent with the microscopic examination and successfully differentiated between the 2-hookworm species. In conclusion, the developed method is a rapid, sensitive and accurate technique and can provide a promising tool for clinical detection and epidemiological investigation of cat-derived hookworms.
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http://dx.doi.org/10.3347/kjp.2019.57.1.9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6409220PMC
February 2019

Aberrant differential expression of EZH2 and H3K27me3 in extranodal NK/T-cell lymphoma, nasal type, is associated with disease progression and prognosis.

Hum Pathol 2019 01 13;83:166-176. Epub 2018 Sep 13.

Department of Pathology, Peking University First Hospital, Beijing 100034, China. Electronic address:

Enhancer of zeste homolog 2 (EZH2), an H3K27-specific histone methyltransferase, has been shown to be frequently overexpressed in various human cancers including lymphoma. Here we investigate the expression and functionality of EZH2 and H3K27me3 in extranodal NK/T-cell lymphoma, nasal type (ENKTL). Results of NanoString analysis revealed that EZH2 and related histone H3 families were up-regulated genes in ENKTL tissues. Results of immunohistochemistry demonstrated that EZH2 and trimethylation of Lys-27 in histone (H3K27me3) were highly expressed in 55.2% and 78.0% of patients with ENKTL, respectively. EZH2 overexpression was significantly associated with higher tumor cell proliferation (r = 0.582, P = .000), advanced stage (P = .012), and predicted poorer overall survival (P = .016) in ENKTL. H3K27me3-positive expression was correlated with lower tumor cell proliferation (r = -0.623, P = .036), earlier stage (P = .043), and predicted better overall survival (P = .020). In addition, EZH2 and H3K27me3 showed inverse correlations (r = -0.652, P = .002) in clinical samples by immunohistochemistry. Furthermore, inhibition of EZH2 by 3-deazaneplanocin A significantly suppressed tumor cell growth. Interestingly, pharmacologic suppression of the JAK3/STAT3 pathway effectively reduced EZH2 and enhanced H3K27me3 in NK/T tumor cell lines. Our data suggest that EZH2 and H3K27me3 are important prognostic markers and potential therapeutic targets in ENKTL.
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http://dx.doi.org/10.1016/j.humpath.2018.08.025DOI Listing
January 2019

Bifunctional aptamer-mediated catalytic hairpin assembly for the sensitive and homogenous detection of rare cancer cells.

Anal Chim Acta 2018 Oct 4;1029:58-64. Epub 2018 May 4.

Department of Laboratory Medicine/Guangdong Engineering and Technology Research Center for Rapid Diagnostic Biosensors, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong Province, PR China. Electronic address:

The presence of cancer cells in body fluids confirms the occurrence of metastasis and guides treatment. A simple, fast, and homogeneous fluorescent method was developed to detect cancer cells based on catalytic hairpin assembly (CHA) and bifunctional aptamers. The bifunctional aptamer had a recognition domain for binding to target cancer cells and an initiator domain for triggering the CHA reaction. In the presence of target cells, the bifunctional aptamer was released from the inhibitor and initiated a cascade reaction of assembly and disassembly of the hairpins. Separation of the fluorophores from the quenchers produced fluorescence signals. The proposed strategy showed high specificity for discriminating normal cells and leukocytes, and the detection limit was 10 cells/mL, which was lower than that of previous aptasensors. This assay was further tested using four kinds of clinical samples spiked with target cells to confirm its applicability. We developed a simple, rapid, and cost-effective method for the detection of cancer cells that did not require purification, and the approach holds great potential for bioanalysis and early diagnosis.
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http://dx.doi.org/10.1016/j.aca.2018.04.068DOI Listing
October 2018

Long non-coding RNA UBE2CP3 enhances HCC cell secretion of VEGFA and promotes angiogenesis by activating ERK1/2/HIF-1α/VEGFA signalling in hepatocellular carcinoma.

J Exp Clin Cancer Res 2018 Jun 4;37(1):113. Epub 2018 Jun 4.

Department of Laboratory Medicine Center, Nanfang Hospital, Southern Medical University/The First School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, China.

Background: Angiogenesis is considered as an important process in the development of malignancies and is associated with cancer progression and metastasis. Hepatocellular carcinoma (HCC) is the most common primary tumor of the liver and is recognized as a typical angiogenic tumor. Thus, it is of great importance to study the underlying mechanism of angiogenesis in HCC. The long non-coding RNA (lncRNA) ubiquitin conjugating enzyme E2C pseudogene 3 (UBE2CP3) has been reported as an oncogene that promotes tumor metastasis in HCC. However, the role and underlying mechanisms of UBE2CP3 in HCC angiogenesis are still unclear.

Methods: We measured the expression levels of UBE2CP3 by in situ hybridization (ISH) and quantitative real-time polymerase chain reaction (qRT-PCR) in HCC patient samples. We also concomitantly used CD31/PAS double-staining to measure endothelial vessel (EV) density and used qRT-PCR to measure the CD31 mRNA level. HepG2 and SMMC-7721 cells were transfected with Lv-UBE2CP3 or Sh-UBE2CP3 virus to obtain stably over-expressing or knocking-down UBE2CP3 cell lines. The indirect effects of UBE2CP3 on ECs were studied by establishing a co-culture system using Transwell chambers with a 0.4-μm pore size. HCC cells and ECs in the co-culture system were separated, but the cytokines and growth factors were able to communicate with each other. Following exposed to HCC cells, ECs were collected for functional studies. Finally, we studied the function of UBE2CP3 in vivo by chick embryo chorioallantoic membrane (CAM) angiogenesis assays and nude mouse tumorigenicity assays.

Results: In this study, we found that UBE2CP3 expression was higher in HCC tissues than in para-tumor tissues and was up-regulated in tissues with high EV density. Functionally, we found that in the co-culture systems, HCC cells overexpressing UBE2CP3 promoted HUVEC proliferation, migration and tube formation via the activation of ERK/HIF-1α/p70S6K/VEGFA signalling, increasing the level of VEGFA in HCC cell supernatant. In addition, the opposite results appeared when the expression of UBE2CP3 in HCC cells was knocked down. Consistent with these results, CAM angiogenesis assays and nude mouse tumorigenicity assays showed that UBE2CP3 expression up-regulated EV density in vivo.

Conclusion: Our study suggests that UBE2CP3 can enhance the interaction between HCC tumor cells and HUVECs and promote HCC tumorigenicity by facilitating angiogenesis.
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http://dx.doi.org/10.1186/s13046-018-0727-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5987644PMC
June 2018

Impact of Heavy Metal Pollution on Ammonia Oxidizers in Soils in the Vicinity of a Tailings Dam, Baotou, China.

Bull Environ Contam Toxicol 2018 Jul 9;101(1):110-116. Epub 2018 May 9.

School of Life Science and Technology, Inner Mongolia University of Science and Technology, Baotou, 014010, China.

Soil heavy metal pollution has received increasing attention due to their toxicity to soil microorganisms. We have analyzed the effects of heavy metal pollution on ammonia-oxidizing archaea (AOA) and ammonia-oxidizing bacteria (AOB) in soils in the vicinity of a tailings dam of Baotou region, China. Results showed that AOB were dominated with Nitrosomonas-like clusters, while AOA was dominated by group1.1b (Nitrososphaera cluster). Single Cd and Cr contents, as well as compound heavy metal pollution levels, had a significant negative impact on soil potential nitrification rate and both diversities of AOA and AOB. No clear relationship was found between any single heavy metal and abundance of AOA or AOB. But compound pollution could significantly decrease AOA abundance. The results indicated that heavy metal pollution had an obviously deleterious effect on the abundance, diversity, activity and composition of ammonia oxidizers in natural soils.
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http://dx.doi.org/10.1007/s00128-018-2345-1DOI Listing
July 2018

Flubendazole inhibits glioma proliferation by G2/M cell cycle arrest and pro-apoptosis.

Cell Death Discov 2018 Dec 14;4:18. Epub 2018 Feb 14.

1Department of Pathogen Biology and Experimental teaching center of Preventive Medicine, Guangdong Provincial Key Laboratory of Tropical Disease, School of Public Health, Southern Medical University, Guangzhou, 510515 China.

Flubendazole, FDA-approved anthelmintic, has been widely used in treating testinal parasites. In the recent years, Flubendazole has been reported to exert anticancer activities. On the other hand, little was known about the effects of Flubendazole on gliomas. Here we demonstrated a novel effect of flubendazole on glioma cells. We found that Flubendazole inhibited cell proliferation and promoted cell apoptosis of glioma cell lines in vitro, and suppressed tumor growth in xenograft models by intraperitoneal injection. However, Flubendazole might have no influence on cell migration. Mechanism study reaveled that Flubendazole caused cell cycle arrest in G2/M phase, which partly account for the suppressed proliferation. Consistently, Flubendazole induced P53 expression and reduced Cyclin B1 and p-cdc2 expression in glioma cells. In addition, Flubendazole promoted cell apoptosis by regulating the classical apoptosis protein BCL-2 expression. These observations suggest that Flubendazole exerts anti-proliferation and pro-apoptosis effects in Glioma through affecting the cell cycle and intrinsic apoptotic signaling, and indicate a novel utilization of Flubendazole in the treatment of Glioma.
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http://dx.doi.org/10.1038/s41420-017-0017-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5841417PMC
December 2018

A novel electrochemical cytosensor for selective and highly sensitive detection of cancer cells using binding-induced dual catalytic hairpin assembly.

Biosens Bioelectron 2018 Apr 7;102:568-573. Epub 2017 Dec 7.

Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, PR China; Guangdong Engineering and Technology Research Center for Rapid Diagnostic Biosensors, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, PR China. Electronic address:

Rare cancer cells in body fluid could be useful biomarkers for noninvasive diagnosis of cancer. However, detection of these rare cells is currently challenging. In this work, a binding-induced dual catalytic hairpin assembly (DCHA) electrochemical cytosensor was developed for highly selective and sensitive detection of cancer cells. The fuel probe, released by hybridization between the capture probe and catalytic hairpin assembly (CHA) products of target cell-responsive reaction, initiated dual CHA recycling, leading to multiple CHA products. Furthermore, the hybridization between fuel probe and capture probe decreased non-specific CHA products, improving the signal-to-noise ratio and detection sensitivity. Under the optimal conditions, the developed cytosensor was able to detect cells down to 30 cells mL (S/N = 3) with a linear range from 50 to 100,000 cells mL and was capable of distinguishing target cells from normal cells in clinical blood samples.
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http://dx.doi.org/10.1016/j.bios.2017.12.010DOI Listing
April 2018

Hypermethylation of PRDM1/Blimp-1 promoter in extranodal NK/T-cell lymphoma, nasal type: an evidence of predominant role in its downregulation.

Hematol Oncol 2017 Dec 5;35(4):645-654. Epub 2016 Oct 5.

Department of Pathology, Peking University First Hospital, Beijing, 100034, China.

The loss of PRDM1 expression is common in extranodal NK/T-cell lymphoma, nasal type (EN-NK/T-NT), but the role of promoter methylation in silencing PRDM1 expression remains unclear. Hence, we performed pyrosequencing analysis to evaluate the promoter methylation of PRDM1 gene in vivo and in vitro, to analyze the association between methylation and its expression, and to assess cellular effects of PRDM1 reexpression. The promoter hypermethylation of PRDM1 gene was detected in 11 of 25 EN-NK/T-NT cases (44.0%) and NK92 and NKL cells. The promoter hypermethylation of PRDM1 was significantly correlated with PRDM1 expression in vivo and in vitro, predominantly contributing to the loss of PRDM1 expression compared with genetic deletion and aberrant expression of miR-223 in EN-NK/T-NT. PRDM1 expression was significantly restored by demethylation treatment, which induced cell proliferation suppression, cell cycle arrest, and apoptosis increase. We also found that PRDM1 reexpression could downregulate the expression of Ets-1, T-bet, granzyme B, and c-myc. Our findings demonstrated that the promoter hypermethylation of PRDM1 harbored a predominant role in the downregulation of PRDM1 expression, significantly affecting the biological behavior of tumor cells in EN-NK/T-NT.
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http://dx.doi.org/10.1002/hon.2362DOI Listing
December 2017

Application of an integrated biomarker response index to assess ground water contamination in the vicinity of a rare earth mine tailings site.

Environ Sci Pollut Res Int 2016 Sep 26;23(17):17345-56. Epub 2016 May 26.

School of Life Science and Technology, Inner Mongolia University of Scientific and Technical, Baotou, 014010, China.

We utilized a multi-biomarker approach (Integrated Biomarker Response version 2, IBRv2) to investigate the scope and dispersion of groundwater contamination surrounding a rare earth mine tailings impoundment. Parameters of SD rat included in our IBRv2 analyses were glutathione levels, superoxide dismutase, catalase, and glutathione peroxidase activities, total anti-oxidative capacity, chromosome aberration, and micronucleus formation. The concentration of 20 pollutants including Cl(-), SO4 (2-), Na(+), K(+), Mg(2+), Ca(2+), TH, CODMn, As, Se, TDS, Be, Mn, Co, Ni, Cu, Zn, Mo, Cd, and Pb in the groundwater were also analyzed. The results of this study indicated that groundwater polluted by tailings impoundment leakage exhibited significant ecotoxicological effects. The selected biomarkers responded sensitively to groundwater pollution. Analyses showed a significant relationship between IBRv2 values and the Nemerow composite index. IBRv2 could serve as a sensitive ecotoxicological diagnosis method for assessing groundwater contamination in the vicinity of rare earth mine tailings. According to the trend of IBRv2 value and Nemerow composite index, the maximum diffusion distance of groundwater pollutants from rare earth mine tailings was approximately 5.7 km.
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http://dx.doi.org/10.1007/s11356-016-6728-8DOI Listing
September 2016

A target-triggered dual amplification strategy for sensitive detection of microRNA.

Biosens Bioelectron 2016 Sep 19;83:250-5. Epub 2016 Apr 19.

Department of Laboratory Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, PR China; Guangdong Engineering and Technology Research Center for Rapid Diagnostic Biosensors, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, PR China. Electronic address:

The accurate and quantitative analysis of microRNA (miRNA) expression is critical for biomedical research and clinical theranostics. In this study, we report a novel sensor for the sensitive detection of miRNA based on a duplex-specific nuclease (DSN)-assisted dual signal amplification strategy. A chimeric probe (DNA/2-OMe-RNA) that consists of a miRNA recognition DNA sequence and a Taqman probe hybridization RNA sequence (2'-O-methyl RNA) was designed and synthesized. One molecule of target miRNA can trigger cyclical cleavage of the chimeric probes to produce 2'-O-methyl RNA by DSN in the first round of amplification. The 2'-O-methyl RNA molecules can subsequently hybridize with Taqman probes and initiate the second round of cyclical amplification to generate detectable fluorescence by DSN. The proposed strategy exhibits high specificity in discriminating cognate miRNAs, and the dual signal transduction process enables the detection of miRNA concentrations as low as 7.3fM. We further applied this assay to miRNA quantification in cancer cells to confirm its applicability. The present study provides a sensitive, specific and simple method for miRNA detection and holds great potential for further application in biomedical research and in the clinical laboratory.
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http://dx.doi.org/10.1016/j.bios.2016.04.053DOI Listing
September 2016

Health risks of metals in contaminated farmland soils and spring wheat irrigated with Yellow River water in Baotou, China.

Bull Environ Contam Toxicol 2015 Feb 5;94(2):214-9. Epub 2014 Dec 5.

The Institute of Bioengineering and Technology, Inner Mongolia University of Science and Technology, Baotou, China.

The consumption of water and food crops contaminated with metals is a major food chain route for human exposure. We investigated the health risks of metals in Yellow River (YR) water, farmland soil and spring wheat in the Baotou region, northern China. Data indicated that long-term irrigation with polluted YR water led to metal accumulation in local farmland soil and spring wheat. The consumption of YR water and spring wheat in Baotou region can cause adverse health effects to local people, specifically because of Hg, Pb, and Se in YR water and Cu, Zn, Cd, and Mn in spring wheat. The integrative risk of various metals depends mainly on the spring wheat intake. Current results emphasized the need for routine monitoring and management in order to avoid contamination of YR water and spring wheat from the wastewater irrigation system in Baotou region.
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http://dx.doi.org/10.1007/s00128-014-1435-yDOI Listing
February 2015