共查询到20条相似文献,搜索用时 15 毫秒
1.
Shigeki Nanjo Tadaaki Yamada Hiroshi Nishihara Shinji Takeuchi Takako Sano Takayuki Nakagawa Daisuke Ishikawa Lu Zhao Hiromichi Ebi Kazuo Yasumoto Kunio Matsumoto Seiji Yano 《PloS one》2013,8(12)
Purpose
Although EGF receptor tyrosine kinase inhibitors (EGFR-TKI) have shown dramatic effects against EGFR mutant lung cancer, patients ultimately develop resistance by multiple mechanisms. We therefore assessed the ability of combined treatment with the Met inhibitor crizotinib and new generation EGFR-TKIs to overcome resistance to first-generation EGFR-TKIs.Experimental Design
Lung cancer cell lines made resistant to EGFR-TKIs by the gatekeeper EGFR-T790M mutation, Met amplification, and HGF overexpression and mice with tumors induced by these cells were treated with crizotinib and a new generation EGFR-TKI.Results
The new generation EGFR-TKI inhibited the growth of lung cancer cells containing the gatekeeper EGFR-T790M mutation, but did not inhibit the growth of cells with Met amplification or HGF overexpression. In contrast, combined therapy with crizotinib plus afatinib or WZ4002 was effective against all three types of cells, inhibiting EGFR and Met phosphorylation and their downstream molecules. Crizotinib combined with afatinib or WZ4002 potently inhibited the growth of mouse tumors induced by these lung cancer cell lines. However, the combination of high dose crizotinib and afatinib, but not WZ4002, triggered severe adverse events.Conclusions
Our results suggest that the dual blockade of mutant EGFR and Met by crizotinib and a new generation EGFR-TKI may be promising for overcoming resistance to reversible EGFR-TKIs but careful assessment is warranted clinically. 相似文献2.
Marine Gilabert Simon Launay Christophe Ginestier Fran?ois Bertucci Stéphane Audebert Mathieu Pophillat Yves Toiron Emilie Baudelet Pascal Finetti Tetsuro Noguchi Hagay Sobol Daniel Birnbaum Jean-Paul Borg Emmanuelle Charafe-Jauffret Anthony Gon?alves 《PloS one》2014,9(8)
Background
Breast cancer stem cells (BCSCs) have been recognized as playing a major role in various aspects of breast cancer biology. To identify specific biomarkers of BCSCs, we have performed comparative proteomics of BCSC-enriched and mature cancer cell populations from the human breast cancer cell line (BCL), BrCA-MZ-01.Methods
ALDEFLUOR assay was used to sort BCSC-enriched (ALDH+) and mature cancer (ALDH−) cell populations. Total proteins were extracted from both fractions and subjected to 2-Dimensional Difference In-Gel Electrophoresis (2-D DIGE). Differentially-expressed spots were excised and proteins were gel-extracted, digested and identified using MALDI-TOF MS.Results
2-D DIGE identified poly(ADP-ribose) polymerase 1 (PARP1) as overexpressed in ALDH+ cells from BrCA-MZ-01. This observation was confirmed by western blot and extended to four additional human BCLs. ALDH+ cells from BRCA1-mutated HCC1937, which had the highest level of PARP1 overexpression, displayed resistance to olaparib, a specific PARP1 inhibitor.Conclusion
An unbiased proteomic approach identified PARP1 as upregulated in ALDH+, BCSC-enriched cells from various human BCLs, which may contribute to clinical resistance to PARP inhibitors. 相似文献3.
Rubens Monte-Neto Marie-Claude N. Laffitte Philippe Leprohon Priscila Reis Frédéric Frézard Marc Ouellette 《PLoS neglected tropical diseases》2015,9(2)
Background
Antimony resistance complicates the treatment of infections caused by the parasite Leishmania.Methodology/Principal Findings
Using next generation sequencing, we sequenced the genome of four independent Leishmania guyanensis antimony-resistant (SbR) mutants and found different chromosomal alterations including aneuploidy, intrachromosomal gene amplification and gene deletion. A segment covering 30 genes on chromosome 19 was amplified intrachromosomally in three of the four mutants. The gene coding for the multidrug resistance associated protein A involved in antimony resistance was also amplified in the four mutants, most likely through chromosomal translocation. All mutants also displayed a reduced accumulation of antimony mainly due to genomic alterations at the level of the subtelomeric region of chromosome 31 harboring the gene coding for the aquaglyceroporin 1 (LgAQP1). Resistance involved the loss of LgAQP1 through subtelomeric deletions in three mutants. Interestingly, the fourth mutant harbored a single G133D point mutation in LgAQP1 whose role in resistance was functionality confirmed through drug sensitivity and antimony accumulation assays. In contrast to the Leishmania subspecies that resort to extrachromosomal amplification, the Viannia strains studied here used intrachromosomal amplification and locus deletion.Conclusions/Significance
This is the first report of a naturally occurred point mutation in AQP1 in antimony resistant parasites. 相似文献4.
Chun-Chi Lai Yung-Hsin Yeh Wen-Ping Hsieh Chi-Tai Kuo Wen-Ching Wang Chia-Han Chu Chiu-Lien Hung Chia-Yang Cheng Hsin-Yi Tsai Jia-Lin Lee Chuan-Yi Tang Lung-An Hsu 《PloS one》2013,8(12)
Background
Inherited cardiac conduction diseases (CCD) are rare but are caused by mutations in a myriad of genes. Recently, whole-exome sequencing has successfully led to the identification of causal mutations for rare monogenic Mendelian diseases.Objective
To investigate the genetic background of a family affected by inherited CCD.Methods and Results
We used whole-exome sequencing to study a Chinese family with multiple family members affected by CCD. Using the pedigree information, we proposed a heterozygous missense mutation (c.G695T, Gly232Val) in the lamin A/C (LMNA) gene as a candidate mutation for susceptibility to CCD in this family. The mutation is novel and is expected to affect the conformation of the coiled-coil rod domain of LMNA according to a structural model prediction. Its pathogenicity in lamina instability was further verified by expressing the mutation in a cellular model.Conclusions
Our results suggest that whole-exome sequencing is a feasible approach to identifying the candidate genes underlying inherited conduction diseases. 相似文献5.
Li-rong Yan Dong-xue Wang Hong Liu Xiao-xing Zhang Hui Zhao Lu Hua Ping Xu Yi-shi Li 《PloS one》2014,9(5)
Objectives
This study aims to compare the protein composition of high-density lipoprotein (HDL) particles in coronary heart disease (CHD) patients and controls by proteomic methods.Background
HDL has been reported to exert pro-atherogenic properties in CHD patients. Accumulating evidence indicates that HDL composition, rather than the HDL-C level, determines its functions. The changes in HDL composition involved in the conversion of anti-atherogenic to pro-atherogenic properties in CHD patients are currently unknown.Methods and Results
iTRAQ combined with nanoLC-MS/MS was performed to obtain a differential expression profile of the HDL pooled samples of the male age-matched CHD patients and controls (n = 10/group). Of the 196 proteins identified in the examined HDL, 12 were differentially expressed between the CHD patients and the controls, including five up-regulated proteins and seven down-regulated proteins. Using GO analysis, we determined that the up-regulated proteins were mostly involved in inflammatory reactions, displaying a potential pro-atherogenic profile. In contrast, the down-regulated proteins were mostly involved in lipid metabolism processes, displaying anti-atherogenic properties. To confirm the proteomic results, serum amyloid A (SAA) and apoC-I were selected and quantified by ELISA, in the same population as the proteomic analysis, as well as another independent population (n = 120/group). Consistent with the proteomic results, the amount of SAA was significantly increased, and apoC-I was significantly decreased in the HDL particles of CHD patients compared with those of controls (P<0.05).Conclusions
Our study shows that the HDL proteome changes to a pro-atherogenic profile in CHD patients, which might compromise the protective effects of HDL. Proteomic analysis of HDL composition may provide more relevant information regarding their functional properties than steady-state HDL-C levels. 相似文献6.
Objectives
To establish whether blueberry (Vaccinium ashei) and mulberry (Morus australis Poir) juice, anthocyanin rich fruit juice, may help counteract obesity.Design
And Methods: Four-week-old C57BL/6 mice were fed a high-fat diet (HFD) with or without blueberry and mulberry juice for 12 weeks. Body weight, serum and hepatic lipids, liver and adipose tissues morphology, insulin and leptin were assessed.Results
Mice fed HFD exhibited increased body weight, insulin resistance, serum and hepatic lipids. In comparison, blueberry and mulberry juice inhibited body weight gain, decreased the serum cholesterol, reduced the resistance to insulin, attenuated lipid accumulation and decreased the leptin secretin.Conclusion
These results indicate that blueberry and mulberry juice may help counteract obesity. 相似文献7.
Yih-Yuan Chen Jia-Ru Chang Shu-Chen Kuo Fan-Chen Tseng Wei-Chen Huang Tsi-Shu Huang Yao-Shen Chen Tzong-Shi Chiueh Jun-Ren Sun Ih-Jen Su Horng-Yunn Dou 《PloS one》2015,10(1)
Background
We present the first comprehensive analysis of Mycobacterium tuberculosis (MTB) isolates circulating in southern Taiwan. In this 9-year population-based study, the TB situation in the Kaohsiung region was characterized by genotypic analysis of 421 MTB isolates.Methods
All 421 isolates of MTB were analyzed by spoligotyping and MIRU-VNTR typing. Drug-resistance patterns were also analyzed.Results
The percentage of EAI (East African-Indian) strains increased across sampling years (2000–2008) in southern Taiwan, whereas the proportion of Beijing lineages remained unchanged. Clustering was more frequent with EAI genotype infections (odds ratio = 3.6, p<0.0001) when compared to Beijing genotypes. Notably, MTB resistance to streptomycin (STR) had significantly increased over time, but resistance to other antibiotics, including multidrug resistance, had not. Three major genes (gidB, rpsL and rrs) implicated in STR resistance were sequenced and specific mutations identified.Conclusions
This study revealed that EAI strains were highly transmissible and that STR resistance has increased between 2000 and 2008 in Kaohsiung, Taiwan. 相似文献8.
9.
Akiko Shiotani Takahisa Murao Yoshihiko Fujita Yoshinori Fujimura Takashi Sakakibara Kazuto Nishio Ken Haruma 《PloS one》2013,8(12)
Background
Aspirin-induced enteropathy is now increasingly being recognized although the pathogenesis of small intestinal damage induced by aspirin is not well understood and related risk factors have not been established.Aim
To investigate pharmacogenomic profile of low dose aspirin (LDA)-induced small bowel bleeding.Methods
Genome-wide analysis of single nucleotide polymorphisms (SNPs) was performed using the Affymetrix DMET™ Plus Premier Pack. Genotypes of candidate genes associated with small bowel bleeding were determined using TaqMan SNP Genotyping Assay kits and direct sequencing.Results
In the validation study in overall 37 patients with small bowel bleeding and 400 controls, 4 of 27 identified SNPs: CYP4F11 (rs1060463) GG (p=0.003), CYP2D6 (rs28360521) GG (p=0.02), CYP24A1 (rs4809957) T allele (p=0.04), and GSTP1 (rs1695) G allele (p=0.04) were significantly more frequent in the small bowel bleeding group compared to the controls. After adjustment for significant factors, CYP2D6 (rs28360521) GG (OR 4.11, 95% CI. 1.62 -10.4) was associated with small bowel bleeding.Conclusions
CYP4F11 and CYP2D6 SNPs may identify patients at increased risk for aspirin-induced small bowel bleeding. 相似文献10.
11.
do Monte-Neto RL Coelho AC Raymond F Légaré D Corbeil J Melo MN Frézard F Ouellette M 《PLoS neglected tropical diseases》2011,5(5):e1167
Background
Drug resistance is a major problem in leishmaniasis chemotherapy. RNA expression profiling using DNA microarrays is a suitable approach to study simultaneous events leading to a drug-resistance phenotype. Genomic analysis has been performed primarily with Old World Leishmania species and here we investigate molecular alterations in antimony resistance in the New World species L. amazonensis.Methods/Principal Findings
We selected populations of L. amazonensis promastigotes for resistance to antimony by step-wise drug pressure. Gene expression of highly resistant mutants was studied using DNA microarrays. RNA expression profiling of antimony-resistant L. amazonensis revealed the overexpression of genes involved in drug resistance including the ABC transporter MRPA and several genes related to thiol metabolism. The MRPA overexpression was validated by quantitative real-time RT-PCR and further analysis revealed that this increased expression was correlated to gene amplification as part of extrachromosomal linear amplicons in some mutants and as part of supernumerary chromosomes in other mutants. The expression of several other genes encoding hypothetical proteins but also nucleobase and glucose transporter encoding genes were found to be modulated.Conclusions/Significance
Mechanisms classically found in Old World antimony resistant Leishmania were also highlighted in New World antimony-resistant L. amazonensis. These studies were useful to the identification of resistance molecular markers. 相似文献12.
Mari Miyamoto Daisuke Motooka Kazuyoshi Gotoh Takamasa Imai Kazutoshi Yoshitake Naohisa Goto Tetsuya Iida Teruo Yasunaga Toshihiro Horii Kazuharu Arakawa Masahiro Kasahara Shota Nakamura 《BMC genomics》2014,15(1)
Background
The availability of diverse second- and third-generation sequencing technologies enables the rapid determination of the sequences of bacterial genomes. However, identifying the sequencing technology most suitable for producing a finished genome with multiple chromosomes remains a challenge. We evaluated the abilities of the following three second-generation sequencers: Roche 454 GS Junior (GS Jr), Life Technologies Ion PGM (Ion PGM), and Illumina MiSeq (MiSeq) and a third-generation sequencer, the Pacific Biosciences RS sequencer (PacBio), by sequencing and assembling the genome of Vibrio parahaemolyticus, which consists of a 5-Mb genome comprising two circular chromosomes.Results
We sequenced the genome of V. parahaemolyticus with GS Jr, Ion PGM, MiSeq, and PacBio and performed de novo assembly with several genome assemblers. Although GS Jr generated the longest mean read length of 418 bp among the second-generation sequencers, the maximum contig length of the best assembly from GS Jr was 165 kbp, and the number of contigs was 309. Single runs of Ion PGM and MiSeq produced data of considerably greater sequencing coverage, 279× and 1,927×, respectively. The optimized result for Ion PGM contained 61 contigs assembled from reads of 77× coverage, and the longest contig was 895 kbp in size. Those for MiSeq were 34 contigs, 58× coverage, and 733 kbp, respectively. These results suggest that higher coverage depth is unnecessary for a better assembly result. We observed that multiple rRNA coding regions were fragmented in the assemblies from the second-generation sequencers, whereas PacBio generated two exceptionally long contigs of 3,288,561 and 1,875,537 bps, each of which was from a single chromosome, with 73× coverage and mean read length 3,119 bp, allowing us to determine the absolute positions of all rRNA operons.Conclusions
PacBio outperformed the other sequencers in terms of the length of contigs and reconstructed the greatest portion of the genome, achieving a genome assembly of “finished grade” because of its long reads. It showed the potential to assemble more complex genomes with multiple chromosomes containing more repetitive sequences.Electronic supplementary material
The online version of this article (doi:10.1186/1471-2164-15-699) contains supplementary material, which is available to authorized users. 相似文献13.
Dong-Liang Mu Li-Huan Li Dong-Xin Wang Nan Li Guo-Jin Shan Jun Li Qin-Jun Yu Chun-Xia Shi 《PloS one》2013,8(10)
Context
Stress response induced by surgery is proposed to play an important role in the pathogenesis of postoperative cognitive dysfunction.Objective
To investigate the association between postoperative serum cortisol level and occurrence of cognitive dysfunction early after coronary artery bypass graft surgery.Design
Prospective cohort study.Setting
Two teaching hospitals.Patients
One hundred and sixth-six adult patients who were referred to elective coronary artery bypass graft surgery from March 2008 to December 2009.Intervention
None.Main Outcome Measures
Neuropsychological tests were completed one day before and seven days after surgery. Cognitive dysfunction was defined using the same definition as used in the ISPOCD1-study. Blood samples were obtained in the first postoperative morning for measurement of serum cortisol concentration. Multivariate Logistic regression analyses were performed to assess the relationship between serum cortisol level and occurrence of postoperative cognitive dysfunction.Results
Cognitive dysfunction occurred in 39.8% (66 of 166) of patients seven days after surgery. Multivariate Logistic regression analysis showed that high serum cortisol level was significantly associated with the occurrence of postoperative cognitive dysfunction (odds ratio [OR] 2.603, 95% confidence interval [CI] 1.371-4.944, P = 0.003). Other independent predictors of early postoperative cognitive dysfunction included high preoperative New York Heart Association functional class (OR 0.402, 95% CI 0.207-0.782, P = 0.007), poor preoperative Grooved Pegboard test score of nondominant hand (OR 1.022, 95% CI 1.003-1.040, P = 0.020), use of penehyclidine as premedication (OR 2.565, 95% CI 1.109-5.933, P = 0.028), and occurrence of complications within seven days after surgery (OR 2.677, 95% CI 1.201-5.963, P = 0.016).Conclusions
High serum cortisol level in the first postoperative morning was associated with increased risk of cognitive dysfunction seven days after coronary artery bypass graft surgery. 相似文献14.
Jinxiang Wu Fangzheng Dong Rui-An Wang Junfei Wang Jiping Zhao Mengmeng Yang Wenbin Gong Rutao Cui Liang Dong 《PloS one》2013,8(10)
Background
Airway remodeling is a repair process that occurs after injury resulting in increased airway hyper-responsiveness in asthma. Thymic stromal lymphopoietin (TSLP), a vital cytokine, plays a critical role in orchestrating, perpetuating and amplifying the inflammatory response in asthma. TSLP is also a critical factor in airway remodeling in asthma.Objectives
To examine the role of TSLP-induced cellular senescence in airway remodeling of asthma in vitro and in vivo.Methods
Cellular senescence and airway remodeling were examined in lung specimens from patients with asthma using immunohischemical analysis. Both small molecule and shRNA approaches that target the senescent signaling pathways were used to explore the role of cellular senescence in TSLP-induced airway remodeling in vitro. Senescence-Associated β-galactosidase (SA-β-Gal) staining, and BrdU assays were used to detect cellular senescence. In addition, the Stat3-targeted inhibitor, WP1066, was evaluated in an asthma mouse model to determine if inhibiting cellular senescence influences airway remodeling in asthma.Results
Activation of cellular senescence as evidenced by checkpoint activation and cell cycle arrest was detected in airway epithelia samples from patients with asthma. Furthermore, TSLP-induced cellular senescence was required for airway remodeling in vitro. In addition, a mouse asthma model indicates that inhibiting cellular senescence blocks airway remodeling and relieves airway resistance.Conclusion
TSLP stimulation can induce cellular senescence during airway remodeling in asthma. Inhibiting the signaling pathways of cellular senescence overcomes TSLP-induced airway remodeling. 相似文献15.
Jessica M. E. van den Oever Sahila Balkassmi Tim Segboer E. Joanne Verweij Pieter A. van der Velden Dick Oepkes Egbert Bakker Elles M. J. Boon 《PloS one》2013,8(12)
Objectives
RASSF1A has been described to be differentially methylated between fetal and maternal DNA and can therefore be used as a universal sex-independent marker to confirm the presence of fetal sequences in maternal plasma. However, this requires highly sensitive methods. We have previously shown that Pyrophosphorolysis-activated Polymerization (PAP) is a highly sensitive technique that can be used in noninvasive prenatal diagnosis. In this study, we have used PAP in combination with bisulfite conversion to develop a new universal methylation-based assay for the detection of fetal methylated RASSF1A sequences in maternal plasma.Methods
Bisulfite sequencing was performed on maternal genomic (g)DNA and fetal gDNA from chorionic villi to determine differentially methylated regions in the RASSF1A gene using bisulfite specific PCR primers. Methylation specific primers for PAP were designed for the detection of fetal methylated RASSF1A sequences after bisulfite conversion and validated.Results
Serial dilutions of fetal gDNA in a background of maternal gDNA show a relative percentage of ∼3% can be detected using this assay. Furthermore, fetal methylated RASSF1A sequences were detected both retrospectively as well as prospectively in all maternal plasma samples tested (n = 71). No methylated RASSF1A specific bands were observed in corresponding maternal gDNA. Specificity was further determined by testing anonymized plasma from non-pregnant females (n = 24) and males (n = 21). Also, no methylated RASSF1A sequences were detected here, showing this assay is very specific for methylated fetal DNA. Combining all samples and controls, we obtain an overall sensitivity and specificity of 100% (95% CI 98.4%–100%).Conclusions
Our data demonstrate that using a combination of bisulfite conversion and PAP fetal methylated RASSF1A sequences can be detected with extreme sensitivity in a universal and sex-independent manner. Therefore, this assay could be of great value as an addition to current techniques used in noninvasive prenatal diagnostics. 相似文献16.
Purpose
To analyze the clinical characteristics of nontuberculous mycobacterial (NTM) ocular infections and the species-specific in vitro antimicrobial susceptibility.Material and Methods
In 2000 to 2011 at the National Taiwan University Hospital, multilocus sequencing of rpoB, hsp65 and secA was used to identify NTM isolates from ocular infections. The clinical presentation and treatment outcomes were retrospectively compared between species. Broth microdilution method was used to determine the minimum inhibitory concentrations of amikacin (AMK), clarithromycin (CLA), ciprofloxacin (CPF), levofloxacin (LVF), moxifloxacin (MXF) and gatifloxacin (GAF) against all strains. The activities of antimicrobial combinations were assessed by the checkerboard titration method.Results
A total of 24 NTM strains (13 Mycobacterium abscessus and 11 Mycobacterium massiliense) were isolated from 13 keratitis, 10 buckle infections, and 1 canaliculitis cases. Clinically, manifestations and outcomes caused by these two species were similar and surgical intervention was necessary for medically unresponsive NTM infection. Microbiologically, 100% of M. abscessus and 90.9% of M. massiliense ocular isolates were susceptible to amikacin but all were resistant to fluoroquinolones. Inducible clarithromycin resistance existed in 69.3% of M. abscessus but not in M. massiliense isolates. None of the AMK-CLA, AMK-MXF, AMK-GAF, CLA-MXF and CLA-GAF combinations showed synergistic or antagonistic effect against both species in vitro.Conclusions
M. abscessus and M. massiliense are the most commonly identified species for NTM ocular infections in Taiwan. Both species were resistant to fluoroquinolones, susceptible to amikacin, and differ in clarithromycin resistance. Combined antimicrobial treatments showed no interaction in vitro but could be considered in combination with surgical interventions for eradication of this devastating ocular infection. 相似文献17.
18.
Awatif M. Abdulsalam Init Ithoi Hesham M. Al-Mekhlafi Abdulsalam M. Al-Mekhlafi Abdulhamid Ahmed Johari Surin 《PloS one》2013,8(12)
Background
Blastocystis is a genetically diverse and a common intestinal parasite of humans with a controversial pathogenic potential. This study was carried out to identify the Blastocystis subtypes and their association with demographic and socioeconomic factors among outpatients living in Sebha city, Libya.Methods/Findings
Blastocystis in stool samples were cultured followed by isolation, PCR amplification of a partial SSU rDNA gene, cloning, and sequencing. The DNA sequences of isolated clones showed 98.3% to 100% identity with the reference Blastocystis isolates from the Genbank. Multiple sequence alignment showed polymorphism from one to seven base substitution and/or insertion/deletion in several groups of non-identical nucleotides clones. Phylogenetic analysis revealed three assemblage subtypes (ST) with ST1 as the most prevalent (51.1%) followed by ST2 (24.4%), ST3 (17.8%) and mixed infections of two concurrent subtypes (6.7%).Blastocystis
ST1 infection was significantly associated with female (P = 0.009) and low educational level (P = 0.034). ST2 was also significantly associated with low educational level (P= 0.008) and ST3 with diarrhoea (P = 0.008).Conclusion
Phylogenetic analysis of Libyan Blastocystis isolates identified three different subtypes; with ST1 being the predominant subtype and its infection was significantly associated with female gender and low educational level. More extensive studies are needed in order to relate each Blastocystis subtype with clinical symptoms and potential transmission sources in this community. 相似文献19.
Soo Hyun Kim Sung Han Shim Se Ra Sung Kyung A. Lee Jung Yun Shim Dong Hyun Cha Kyoung Jin Lee 《PloS one》2013,8(10)
Background
Despite increasing evidence that human parturition is associated with alteration in gene expression in the uteroplacental unit, the precise mechanisms that elicit spontaneous term labor in humans remain unknown. Our goal in this study was to compare the mRNA expression pattern of the trophoblast layer of normal term placenta between women who had given natural birth (labor group) and those who had undergone an elective cesarean section without labor (non-labor group).Methods
We collected placental tissue samples from six pregnant women after term vaginal deliveries (labor group) and from six pregnant women after scheduled Cesarean sections (non-labor group). Frozen sections were made immediately after placental delivery. Because the placenta is a heterogeneous tissue composed of several cell types, we used laser capture microdissection to separate the trophoblast layer from the rest of the placental tissues.Results
A number of genes were differentially expressed in the trophoblast layer when the labor and non-labor groups were compared. The expression of SIRT1, KAP1, and CRH was significantly lower in the trophoblast layer of the labor group than of the non-labor group. The expression of IL-1b, NF-kB1 and TLR 8 in the labor group was significantly higher than that in the non-labor group.Conclusions
Human term labor may be closely associated with inflammatory response. We suggest that downregulation of SIRT1, KAP1, and CRH gene expression in the trophoblast may play a key role in parturition and initiation of labor in pregnant human females. 相似文献20.
Robin L. P. Jump Alex Polinkovsky Kelly Hurless Brett Sitzlar Kevin Eckart Myreen Tomas Abhishek Deshpande Michelle M. Nerandzic Curtis J. Donskey 《PloS one》2014,9(7)