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author:("Li, xiaohei")
1.  Limited and Localized Outbreak of Newly Emergent Type 2 Vaccine-Derived Poliovirus in Sichuan, China 
From August 2011 to February 2012, an outbreak caused by type 2 circulating vaccine-derived poliovirus (cVDPV) occurred in Aba County, Sichuan, China. During the outbreak, four type 2 VDPVs (≥0.6% nucleotide divergence in the VP1 region relative to the Sabin 2 strain) were isolated from 3 patients with acute flaccid paralysis (AFP) and one close contact. In addition, a type 2 pre-VDPV (0.3% to 0.5% divergence from Sabin 2) that was genetically related to these type 2 VDPVs was isolated from another AFP patient. These 4 patients were all unimmunized children 0.7 to 1.1 years old. Nucleotide sequencing revealed that the 4 VDPV isolates differed from Sabin 2 by 0.7% to 1.2% in nucleotides in the VP1 region and shared 5 nucleotide substitutions with the pre-VDPV. All 5 isolates were closely related, and all were S2/S3/S2/S3 recombinants sharing common recombination crossover sites. Although the two major determinants of attenuation and temperature sensitivity phenotype of Sabin 2 (A481 in the 5′ untranslated region and Ile143 in the VP1 protein) had reverted in all 5 isolates, one VDPV (strain CHN16017) still retained the temperature sensitivity phenotype. Phylogenetic analysis of the third coding position of the complete P1 coding region suggested that the cVDPVs circulated locally for about 7 months following the initiating oral poliovirus vaccine (OPV) dose. Our findings reinforce the point that cVDPVs can emerge and spread in isolated communities with immunity gaps and highlight the emergence risks of type 2 cVDPVs accompanying the trivalent OPV used. To solve this issue, it is recommended that type 2 OPV be removed from the trivalent OPV or that inactivated polio vaccine (IPV) be used instead.
doi:10.1128/CVI.00196-14
PMCID: PMC4097442  PMID: 24850620
2.  Reduction of intraarticular adhesion by topical application of colchicine following knee surgery in rabbits 
Scientific Reports  2014;4:6405.
The aim of this study was to investigate the efficacy of topical application of colchicine in reducing intraarticular adhesion in rabbits. Thirty-six rabbits were randomly and equally divided into three groups. An approximately 10 × 10 mm2 area of cortical bone was removed from both sides of the left femoral condyle, and the cancellous bone underneath was exposed. Cotton pads soaked with different concentrations of colchicine or saline were applied to the decorticated areas for 10 minutes. The surgical limb was fixed in a flexed position for 4 weeks postoperatively. To evaluate knee intraarticular adhesion, we performed macroscopic evaluation, histological and collagen density analyses, hydroxyproline content determination, fibroblast counting and densitometric analyses. The results showed that loose collagen tissues with little or no adhesion were present around the decorticated areas in the group treated with 0.5 mg/ml colchicine. The intraarticular adhesion score, hydroxyproline content, number of fibroblasts and densitometric value in this group were also significantly lower than those in the other groups. There was moderate intraarticular adhesion in the group treated with 0.1 mg/ml colchicine. However, dense scar tissue with dense adhesions was found in the control group. In conclusion, topical application of 0.5 mg/ml colchicine may reduce knee intraarticular adhesion.
doi:10.1038/srep06405
PMCID: PMC4171695  PMID: 25245566
3.  Phylogenetic evidence for multiple intertypic recombinations in enterovirus B81 strains isolated in Tibet, China 
Scientific Reports  2014;4:6035.
Enterovirus B81 (EV-B81) is a newly identified serotype within the species enterovirus B (EV-B). To date, only eight nucleotide sequences of EV-B81 have been published and only one full-length genome sequence (the prototype strain) has been made available in the GenBank database. Here, we report the full-length genome sequences of two EV-B81 strains isolated in the Tibet Autonomous Region of China during acute flaccid paralysis surveillance activities, and we also conducted an antibody seroprevalence study in two prefectures of Tibet. The sequence comparison and phylogenetic dendrogram analysis revealed high variability among the global EV-B81 strains and frequent intertypic recombination in the non-structural protein region of EV-B serotypes, suggesting high genetic diversity of EV-B81. However, low positive rates and low titers of neutralizing antibodies against EV-B81 were detected. Nearly 68% of children under the age of five had no neutralizing antibodies against EV-B81. Hence, the extent of transmission and the exposure of the population to this EV type are very limited. Although little is known about the biological and pathogenic properties of EV-B81 because of few research in this field owing to the limited number of isolates, our study provides basic information for further studies of EV-B81.
doi:10.1038/srep06035
PMCID: PMC4129410  PMID: 25112835
4.  The optimal concentration of topical hydroxycamptothecin in preventing intraarticular scar adhesion 
Scientific Reports  2014;4:4621.
10-Hydroxycamptothecin could reduce intraarticular adhesion by inhibiting fibroblasts proliferation after knee surgery. However, the ideal concentration of hydroxycamptothecin have not been defined. This study was tried to verify the optimal concentration of 10-hydroxycamptothecin in preventing knee intraarticular adhesion. Sixty rabbits were randomly divided into five groups. Approximately 10 mm × 10 mm of the cortical bone was removed from both sides of the femoral condyle and the underneath cancellous bone was exposed. Various concentrations of hydroxycamptothecin (0.1 mg/ml, 0.5 mg/ml, 1.0 mg/ml, 2.0 mg/ml) or saline were applied to the decorticated areas for 10 minutes. After four weeks, the degree of inraarticular adhesion was assessed by macroscopic evaluation, biochemical analysis of hydroxyproline content and histological evaluation. The results demonstrated that the extent of knee inraarticular adhesion in 1.0 mg/ml group and 2.0 mg/ml hydroxycamptothecin group were significantly lower than those of 0.5 mg/ml group, 0.1 mg/ml hydroxycamptothecin group and control group. Moreover, there was no significant difference between 1.0 mg/ml group and 2.0 mg/ml hydroxycamptothecin group. In conclusion, topical application of 1.0 mg/ml hydroxycamptothecin may be the optimal concentration in reducing intraarticular adhesion after knee surgery in rabbits.
doi:10.1038/srep04621
PMCID: PMC3980220  PMID: 24714729
5.  Association of methylenetetrahytrofolate reductase (MTHFR) C677T and A1298C polymorphisms with the susceptibility of childhood acute lymphoblastic leukaemia (ALL) in Chinese population 
Background
The aim of this study was to investigate the relationship between the polymorphisms of the methylenetetrahytrofolate reductase (MTHFR) gene and susceptibility to childhood acute lymphoblastic leukemia (ALL).
Methods
A case–control study was conducted among 98 children with ALL and 93 age- and sex- matched non-ALL controls. Genotyping of MTHFR C677T and A1298C polymorphisms was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The odds ratios (ORs) of MTHFR genotypes were used to assess the associations of these polymorphisms with childhood ALL susceptibility.
Results
No significant differences were observed for frequencies of the 677CC, 677CT and 677TT genotypes between patients and controls. Frequencies of the 1298AA, 1298 AC and 1298CC genotypes between the two groups were significantly different. The risk of ALL with the 1298C allele carriers (AC + CC) was elevated by 1.1 times compared with the AA genotype [OR = 2.100; 95% CI (1.149; 3.837); P = 0.015].
Conclusions
The MTHFR A1298C polymorphism is associated with susceptibility to childhood ALL in the Chinese population.
doi:10.1186/2047-783X-19-5
PMCID: PMC3932997  PMID: 24476575
Methylenetetrahydrofolate reductase (MTHFR); C677T; A1298C; Gene polymorphism; Acute lymphoblastic leukemia
6.  A DNA Element Regulates Drug Tolerance and Withdrawal in Drosophila 
PLoS ONE  2013;8(9):e75549.
Drug tolerance and withdrawal are insidious responses to drugs of abuse; the first increases drug consumption while the second punishes abstention. Drosophila generate functional tolerance to benzyl alcohol sedation by increasing neural expression of the slo BK-type Ca2+ activated K+ channel gene. After drug clearance this change produces a withdrawal phenotype—increased seizure susceptibility. The drug-induced histone modification profile identified the 6b element (60 nt) as a drug responsive element. Genomic deletion of 6b produces the allele, sloΔ6b, that reacts more strongly to the drug with increased induction, a massive increase in the duration of tolerance, and an increase in the withdrawal phenotype yet does not alter other slo-dependent behaviors. The 6b element is a homeostatic regulator of BK channel gene expression and is the first cis-acting DNA element shown to specifically affect the duration of a drug action.
doi:10.1371/journal.pone.0075549
PMCID: PMC3781064  PMID: 24086565
7.  Complete Genome Sequence of Two Coxsackievirus A1 Strains That Were Cytotoxic to Human Rhabdomyosarcoma Cells 
Journal of Virology  2012;86(18):10228-10229.
Coxsackievirus A1 (CVA1) belongs to human enterovirus species C within the family Picornaviridae, order Picornavirales. Two Chinese CVA1 isolates, HT-THLH02F/XJ/CHN/2011 and KS-ZPH01F/XJ/CHN/2011, were isolated from stool specimens of two healthy children in the Xinjiang Uygur autonomous region of China. They were found to elicit cytopathic effects in a human rhabdomyosarcoma cell line, and complete genome sequences of these two CVA1 isolates revealed that natural intertypic recombination events occurred between CVA1 and CVA22.
doi:10.1128/JVI.01567-12
PMCID: PMC3446563  PMID: 22923792
8.  Transmission of Human Enterovirus 85 Recombinants Containing New Unknown Serotype HEV-B Donor Sequences in Xinjiang Uighur Autonomous Region, China 
PLoS ONE  2013;8(1):e55480.
Background
Human enterovirus 85 (HEV85), whose prototype strain (Strain BAN00-10353/BAN/2000) was isolated in Bangladesh in 2000, is a recently identified serotype within the human enterovirus B (HEV-B) species. At present, only one nucleotide sequence of HEV85 (the complete genome sequence of the prototype strain) is available in the GenBank database.
Principal Findings
In this study, we report the genetic characteristics of 33 HEV85 isolates that circulated in the Xinjiang Uighur autonomous region of China in 2011. Sequence analysis revealed that all these Chinese HEV85 isolates belong to 2 transmission chains, and intertypic recombination was found with the new unknown serotype HEV-B donor sequences. Two HEV85 isolates recovered from a patient presenting acute flaccid paralysis and one of his contacts were temperature-insensitive strains, and some nucleotide substitutions in the non-coding regions and in the 2C or 3D coding regions may have affected the temperature sensitivity of HEV85 strains.
Conclusions
The Chinese HEV85 recombinant described in this study trapped a new unknown serotype HEV-B donor sequence, indicating that new unknown HEV-B serotypes exist or circulate in Xinjiang of China. Our study also indicated that HEV85 is a prevalent and common enterovirus serotype in Xinjiang.
doi:10.1371/journal.pone.0055480
PMCID: PMC3561255  PMID: 23383202
9.  Characterization of Adult α- and β-Globin Elevated by Hydrogen Peroxide in Cervical Cancer Cells That Play A Cytoprotective Role Against Oxidative Insults 
PLoS ONE  2013;8(1):e54342.
Objectives
Hemoglobin (Hgb) is the main oxygen and carbon dioxide carrier in cells of erythroid lineage and is responsible for oxygen delivery to the respiring tissues of the body. However, Hgb is also expressed in nonerythroid cells. In the present study, the expression of Hgb in human uterine cervix carcinoma cells and its role in cervical cancer were investigated.
Methodology
The expression level of Hgb in cervical cancer tissues was assessed by quantitative reverse transcriptase-PCR (qRT-PCR). We applied multiple methods, such as RT-PCR, immunoblotting, and immunohistochemical analysis, to confirm Hgb expression in cervical cancer cells. The effects of ectopic expression of Hgb and Hgb mutants on oxidative stress and cell viability were investigated by cellular reactive oxygen species (ROS) analysis and lactate dehydrogenase (LDH) array, respectively. Both Annexin V staining assay by flow cytometry and caspase-3 activity assay were used, respectively, to evaluate cell apoptosis.
Results
qRT-PCR analysis showed that Hgb-α- (HBA1) and Hgb-β-globin (HBB) gene expression was significantly higher in cervical carcinoma than in normal cervical tissues, whereas the expression of hematopoietic transcription factors and erythrocyte specific marker genes was not increased. Immunostaining experiments confirmed the expression of Hgb in cancer cells of the uterine cervix. Hgb mRNA and protein were also detected in the human cervical carcinoma cell lines SiHa and CaSki, and Hgb expression was up-regulated by hydrogen peroxide-induced oxidative stress. Importantly, ectopic expression of wild type HBA1/HBB or HBA1, rather than mutants HBA1H88R/HBBH93R unable to bind hemo, suppressed oxidative stress and improved cell viability.
Conclusions
The present findings show for the first time that Hgb is expressed in cervical carcinoma cells and may act as an antioxidant, attenuating oxidative stress-induced damage in cervical cancer cells. These data provide a significant impact not only in globin biology but also in understanding of cervical cancer pathogenesis associated with oxidative stress.
doi:10.1371/journal.pone.0054342
PMCID: PMC3547883  PMID: 23349856
10.  Complete Genome Sequence of a Novel Human Enterovirus 85 (HEV85) Recombinant with an Unknown New Serotype HEV-B Donor Sequence Isolated from a Child with Acute Flaccid Paralysis 
Genome Announcements  2013;1(1):e00015-12.
A Chinese human enterovirus 85 (HEV85) isolate, HTYT-ARL-AFP02F/XJ/CHN/2011, was isolated from a stool specimen of a child with acute flaccid paralysis in Xinjiang, China, in 2011. The complete genome sequence revealed that a natural intertypic recombination event had occurred between HEV85 and a previously undescribed serotype of HEV-B.
doi:10.1128/genomeA.00015-12
PMCID: PMC3556829  PMID: 23405286
11.  A MicroRNA Component of the Neoplastic Microenvironment: Microregulators with Far-Reaching Impact 
BioMed Research International  2012;2013:762183.
The interplay between tumor cells and their microenvironment plays a pivotal role in tumor development and progression. Although a growing body of evidence has established the importance of the tumor microenvironment, an understanding of the crosstalk between its components and cancer cells remains elusive. The pathways triggered by microenvironmental factors could modulate cancer-related gene transcription, also affecting small noncoding RNAs, microRNAs, which have emerged as key posttranscriptional regulators of gene expression, directly involved in human cancers. Although microRNAs regulate most biological mechanisms, their role in the tumor microenvironment has only recently become the focus of intense research. In this paper, we focus on the intertwined connection between the tumor microenvironment and aberrant expression of microRNAs involved in carcinogenesis. We also discuss the emerging roles of microRNAs in the tumor microenvironment as it relates to cancer progression. We conclude that microRNAs are critical for our understanding of the development of cancer, and that targeting microRNA signaling pathways in the microenvironment as well as in tumor cells opens new therapeutic avenues to the global control of cancer.
doi:10.1155/2013/762183
PMCID: PMC3591172  PMID: 23509776
12.  LRP16 Integrates into NF-κB Transcriptional Complex and Is Required for Its Functional Activation 
PLoS ONE  2011;6(3):e18157.
Background
Nuclear factor κB (NF-κB)-mediated pathways have been widely implicated in cell survival, development and tumor progression. Although the molecular events of determining NF-κB translocation from cytoplasm to nucleus have been extensively documented, the regulatory mechanisms of NF-κB activity inside the nucleus are still poorly understood. Being a special member of macro domain proteins, LRP16 was previously identified as a coactivator of both estrogen receptor and androgen receptor, and as an interactor of NF-κB coactivator UXT. Here, we investigated the regulatory role of LRP16 on NF-κB activation.
Methodology
GST pull-down and coimmunoprecipitation (CoIP) assays assessed protein-protein interactions. The functional activity of NF-κB was assessed by luciferase assays, changes in expression of its target genes, and its DNA binding ability. Annexin V staining and flow cytometry analysis were used to evaluate cell apoptosis. Immunohistochemical staining of LRP16 and enzyme-linked immunosorbent assay-based evaluation of active NF-κB were performed on primary human gastric carcinoma samples.
Results
We demonstrate that LRP16 integrates into NF-κB transcriptional complex through associating with its p65 component. RNA interference knockdown of the endogenous LRP16 in cells leads to impaired NF-κB activity and significantly attenuated NF-κB-dependent gene expression. Mechanistic analysis revealed that knockdown of LRP16 did not affect tumor necrosis factor α (TNF-α)-induced nuclear translocation of NF-κB, but blunted the formation or stabilization of functional NF-κB/p300/CREB-binding protein transcription complex in the nucleus. In addition, knockdown of LRP16 also sensitizes cells to apoptosis induced by TNF-α. Finally, a positive link between LRP16 expression intensity in nuclei of tumor cells and NF-κB activity was preliminarily established in human gastric carcinoma specimens.
Conclusions
Our findings not only indicate that LRP16 is a crucial regulator for NF-κB activation inside the nucleus, but also suggest that LRP16 may be an important contributor to the aberrant activation of NF-κB in tumors.
doi:10.1371/journal.pone.0018157
PMCID: PMC3069058  PMID: 21483817

Results 1-12 (12)