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Jing Yang

Bio: Jing Yang is an academic researcher from Peking University. The author has contributed to research in topics: Medicine & Internal medicine. The author has an hindex of 4, co-authored 10 publications receiving 47 citations.

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Journal ArticleDOI
TL;DR: A nested case-control study to analyze longitudinal gut microbiota alterations in pregnant women with and without PE in the second and third trimesters of pregnancy found that the relative abundance of Bacteroidetes, Proteobacteria, and Enterobacteriaceae were significantly higher in the PE group than in the control group; and these differences were identified as taxonomic biomarkers of PE.
Abstract: BACKGROUND Preeclampsia (PE) is a serious complication that affects maternal and perinatal outcomes. However, the mechanisms have not been fully explained. This study was designed to analyze longitudinal gut microbiota alterations in pregnant women with and without PE in the second (T2) and third trimesters (T3). METHODS In this nested case-control study, which was conducted at Nanjing Maternity and Child Health Care Hospital, fecal samples from 25 PE patients (25 fecal samples obtained in T2 and 15 fecal samples obtained in T3) and 25 matched healthy controls (25 fecal samples obtained in T2 and 22 fecal samples obtained in T3) were collected, and the microbiota were analyzed using 16S rRNA gene sequencing. The diversity and composition of the microbiota of PE cases and controls were compared. RESULTS No significant differences in diversity were found between the PE and control groups (P > 0.05). In the control group, from T2 to T3, the relative abundances of Proteobacteria (median [Q1, Q3]: 2.25% [1.24%, 3.30%] vs. 0.64% [0.20%, 1.20%], Z = -3.880, P < 0.05), and Tenericutes (median [Q1, Q3]: 0.12% [0.03%, 3.10%] vs. 0.03% [0.02%, 0.17%], Z = -2.369, P < 0.05) decreased significantly. In the PE group, the relative abundance of Bacteroidetes in T2 was lower than in T3 (median [Q1, Q3]: 18.16% [12.99%, 30.46%] vs. 31.09% [19.89%, 46.06%], Z = -2.417, P < 0.05). In T2, the relative abundances of mircrobiota showed no significant differences between the PE group and the control group. However, in T3, the relative abundance of Firmicutes was significantly lower in the PE group than in the control group (mean ± standard deviation: 60.62% ± 15.17% vs. 75.57% ± 11.53%, t = -3.405, P < 0.05). The relative abundances of Bacteroidetes, Proteobacteria, and Enterobacteriaceae were significantly higher in the PE group than in the control group (median [Q1, Q3]: 31.09% [19.89%, 46.06%] vs. 18.24% [12.90%, 32.04%], Z = -2.537, P < 0.05; 1.52% [1.05%, 2.61%] vs. 0.64% [0.20%, 1.20%], Z = -3.310, P < 0.05; 0.75% [0.20%, 1.00%] vs. 0.01% [0.004%, 0.023%], Z = -4.152, P < 0.05). Linear discriminant analysis combined effect size measurements analysis showed that the relative abundances of the phylum Bacteroidetes, class Bacteroidia and order Bacteroidales were increased in the PE group, while those of the phylum Firmicutes, the class Clostridia, the order Clostridiales, and the genus unidentified Lachnospiraceae were decreased in the PE group; and these differences were identified as taxonomic biomarkers of PE in T3. CONCLUSION From T2 to T3, there was an obvious alteration in the gut microbiota. The gut microbiota of PE patients in T3 was significantly different from that of the control group.

27 citations

Journal ArticleDOI
Qi Zhang1, Xiangjun He, Li-ping Ma, Na Li, Jing Yang, Ye-xia Cheng, Heng Cui 
TL;DR: As tumor-suppressor microRNAs,miR-449a/b, miR-34b and mi-34c cooperate and play important roles in p53 pathway and may contribute to the carcinogenesis and progression of serous ovarian carcinomas.
Abstract: Objective The aim of this study was to investigate whether miR-449a, miR-449b and miR-192 family microRNAs play the same roles in p53 pathway as miR-34 family in ovarian cancer. Methods Wild-type p53 ovarian carcinoma cell line A2780 cells were treated with genotoxic agent adriamycin. The reactivation of p53 was detected by Western blot. The expression of miR-449a/b, miR- 34a, miR-34b,miR-34c, miR-192 and miR-194 were detected by real-time quantitative PCR. Mutant p53 ovarian cancer cell line SKOV3. ipl cells were transfected with pre-microRNAs and the cell-cycle changes were detected. The expression level of miR-449a/b, miR-34a, miR-34b, miR-34c, miR-192 and miR-194 in serous ovarian carcinomas of varying grade and stage were compared with real-time PCR. Results The expressions of miR-449a/b, miR-34b and miR-34c were 19-fold to 21-fold elevated after p53 activation by genotoxic agent. Ectopic expression of miR-449b, as well as miR-34c, resulted in cell-cycle arrest in SKOV3. ipl cells: The expression of miR-449a/b was parallel with that of miR-34b, miR-34C, and Were significantly lower in late stage and high-grade serous carcinomas than in the normal fallopian tube, early stage and low-grade serous carcinomas. The expression of miR-192, miR-194 and miR-34a did not show evident features in serous ovarian carcinomas and were much lower than miR-449a/b, miR-34b and miR-34c in normal fallopian tube. Conclusions As tumor-suppressor microRNAs, miR-449a/b, miR-34b and miR- 34c cooperate and play important roles in p53 pathway. Their inactivation may contribute to the carcinogenesis and progression of serous ovarian carcinomas. Key words: MicroRNA ; P53 pathway; Ovarian neoplasms

20 citations

Journal Article
Xiang-jun He1, Jing Yang1, Qi Zhang1, Heng Cui1, Yujun Zhang1 
TL;DR: Heterogeneous 3' UTR lengths render HMGA2 susceptible to different levels of negative regulation by microRNAs, which represents an important mechanism ofHMGA2 reactivation in SOC.
Abstract: BACKGROUND: Oncofetal protein high-mobility-group AT-hook protein 2 (HMGA2) is reactivated in serous ovarian cancer (SOC) and its overexpression correlates with poor prognosis. To explore the mechanism, we investigated whether HMGA2 could avoid microRNA regulation due to gene truncation or 3' UTR shortening by alternative polyadenylation. METHODS: Real-time reverse transcription polymerase chain reaction (RT-PCR) was used to evaluate the abundance of different regions of HMGA2 mRNA in 46 SOC samples. Rapid amplification of cDNA 3' ends (3' RACE) and Southern blotting were used to confirm the shortening of 3' untranslated region (UTR). 5' RACE and Southern blotting were used to prove the mRNA decay. RESULTS: No significant difference in the ratio of the stable coding region to the fragile region was observed between SOC and control normal fallopian tubes, indicating that the HMGA2 gene is not truncated in SOC. Varying degrees of 3' UTR shortening in SOC samples were observed by comparing the abundance of the proximal region and distal region of the HMGA2 3' UTR. The ratio of the proximal to the distal region of the 3' UTR correlated significantly with expression of the HMGA2 coding region in SOC (r = 0.579, P < 0.01). Moreover, although the abundance of the HMGA2 coding region varied, all samples, including the very low expressed samples, exhibit relatively high levels of the proximal 3' UTR region, suggesting a dynamic decay of HMGA2 mRNA from the 5' end. The shortening of 3' UTR and the decay from the 5' end were confirmed by 3' RACE, 5' RACE and subsequent Southern blotting. CONCLUSION: Heterogeneous 3' UTR lengths render HMGA2 susceptible to different levels of negative regulation by microRNAs, which represents an important mechanism of HMGA2 reactivation in SOC.

12 citations

Journal ArticleDOI
TL;DR: It is demonstrated that the hair metabolite profiles of the different sIUGR subclinical forms were associated with the averaged fetal growth rate after 28 weeks of gestation but not with birthweight.
Abstract: Selective intrauterine fetal growth restriction (sIUGR) in monochorionic diamniotic twins, especially types 2&3 with abnormal umbilical artery Doppler, results in increased risk of fetal/perinatal mortality and postnatal disability. We investigate whether the hair metabolome profiles of neonates were associated with the pathophysiological differences across the different clinical forms of sIUGR in twins. Hair samples were collected at delivery from 10 pairs of type 1 sIUGR twins, 8 pairs of types 2&3 sIUGR twins, and 11 pairs of twins without sIUGR. The hair metabolome was characterized using gas chromatography-mass spectrometry. Our results demonstrated that the hair metabolite profiles of the different sIUGR subclinical forms were associated with the averaged fetal growth rate after 28 weeks of gestation but not with birthweight. The hair profiles were capable of discriminating type2&3 sIUGR twins from twins without sIUGR. In particular, the metabolites 2-aminobutyric acid, cysteine, alanine, and tyrosine all displayed areas under the receiver operating characteristic curve were above 0.9. The metabolic pathway analysis highlighted the associations of sIUGR twins with abnormal umbilical artery flow with increased metabolites from a nutrient depletion pathway, glutathione metabolism, and nerve development. This study offers novel insight into the severity of intrauterine ischemia and hypoxia for T2&3 sIUGR twins, through evaluation of the neonatal hair metabolome.

12 citations

Journal ArticleDOI
TL;DR: The study uncovered that microbial diversity and components of the meconium microbiome between DZ and MZ twins were partially consistent with that in singleton neonates by cesarean delivery, but several distinctions related to the heritability supported genetic contributions to intestinal microbiome in early life.
Abstract: The early-life microbiota triggers life-long effects on physiological functions and health disorders. Previous studies in adult twins or animal models have revealed associations between host genetics and the harmonious microbiota. However, such associations may be obscured by the fact that each intra-pair of twins will continually encounter various environmental factors as they grow up. Here, we collected the meconium samples from nineteen dizygotic pairs (DZ, n = 38) and nine monozygotic pairs (MZ, n = 18) with cesarean delivery, and 16S rRNA gene sequencing was performed to profile the microbiome at birth. Diversity analysis showed that alpha diversity was not significantly different between two groups, whereas beta diversity of MZ twins was significantly lower than that of either DZ twins or unrelated individuals (i.e., randomly selected individual pairs of non-twinship) (p < 0.05). Two groups had very similar microbial classifications but different relative abundances of certain taxa including more Firmicutes (p = 0.05, Wilcoxon test) at the phylum level and lower abundances of five genera (p < 0.05) in DZ group compared to MZ group, including Rheinheimera, Proteus, SMB53, Sphingobium, and Megamonas. Co-occurrence analysis in each group showed slightly more complicated microbial interactions in DZ than MZ twins, although 22 shared bacterial genera co-existed in two groups, with both Rheinheimera and Megamonas having different centralities in their respective co-occurrence networks. Mean intra-class correlation coefficient (ICC) were also significantly higher for MZ (0.312) compared to DZ twins (0.138) (p < 0.05). The predicted microbial gene functions related to carbohydrate were higher in DZ group, whereas folding, sorting, degradation, cell motility pathways and energy metabolism were markedly over-represented in the microbiota of MZ group. In summary, our study uncovered that microbial diversity and components of the meconium microbiome between DZ and MZ twins were partially consistent with that in singleton neonates by cesarean delivery, but several distinctions related to the heritability supported genetic contributions to intestinal microbiome in early life.

8 citations


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TL;DR: This review will discuss both the currently used serum tumor markers for screening, diagnosis, monitoring of ovarian cancer, and the novel biomarkers that are now under investigation and validation.
Abstract: Serum tumor markers have a major role in the screening, diagnosis, and monitoring of most of the gynecologic cancers. Ovarian cancer is one of the deadliest of the group because it is so frequently asymptomatic until it has advanced to an untreatable stage. Even serum cancer antigen-125 (CA-125), clinically one of the most reliable serum markers for ovarian cancer, is elevated in only half of early-stage still-treatable tumors. Because of the very low prevalence of ovarian cancer in the general population, at present, there is no cost-effective imaging or simple microscopic screening test for ovarian cancer as there is for breast and cervical cancers. However, recent proteomics and nucleic acid-based analyses have shown great promise for the discovery of new and more useful serum biomarkers, which cumulatively might provide such a screening tool. In this review, we will discuss both the currently used serum tumor markers for screening, diagnosis, monitoring of ovarian cancer, and the novel biomarkers that are now under investigation and validation.

94 citations

Journal ArticleDOI
TL;DR: Comparison of corticogenesis, gene expression and behavior in three mouse models of Down syndrome revealed major differences between the models as well as significant limitations in each strain for understanding neurobiological changes in the human phenotype.
Abstract: Down syndrome (DS) results from triplication of human chromosome 21. Neuropathological hallmarks of DS include atypical central nervous system development that manifests prenatally and extends throughout life. As a result, individuals with DS exhibit cognitive and motor deficits and have delays in achieving developmental milestones. To determine whether different mouse models of DS recapitulate the human prenatal and postnatal phenotypes, here we directly compared brain histogenesis, gene expression, and behavior over the lifespan of three cytogenetically distinct mouse models of DS: Ts1Cje, Ts65Dn and Dp(16)1/Yey. Histological data indicated that Ts65Dn mice were the most consistently affected with respect to somatic growth, neurogenesis, and brain morphogenesis. Embryonic and adult gene expression results showed that Ts1Cje and Ts65Dn brains had considerably more differentially expressed (DEX) genes compared to Dp(16)1/Yey mice, despite the larger number of triplicated genes in the latter model. In addition, DEX genes showed little overlap in identity and chromosomal distribution in the three models, leading to dissimilarities in affected functional pathways. Perinatal and adult behavioral testing also highlighted differences among the models in their abilities to achieve various developmental milestones and perform hippocampal- and motor-based tasks. Interestingly, Dp(16)1/Yey mice showed no abnormalities in prenatal brain phenotypes, yet they manifested behavioral deficits starting at postnatal day 15 that continued through adulthood. In contrast, Ts1Cje mice showed mildly abnormal embryonic brain phenotypes, but only select behavioral deficits as neonates and adults. Altogether, our data showed widespread and unexpected fundamental differences in behavioral, gene expression, and brain development phenotypes between these three mouse models. Our findings illustrate unique limitations of each model when studying aspects of brain development and function in DS. This work helps to inform model selection in future studies investigating how observed neurodevelopmental abnormalities arise, how they contribute to cognitive impairment, and when testing therapeutic molecules to ameliorate the intellectual disability associated with DS.

84 citations

Journal ArticleDOI
TL;DR: It is indicated that miR-124 can suppress gastric cancer cell growth by directly targeting the EZH2 gene and sensitize the treatment effect of 5-FU, and may be a new and useful approach of Gastric cancer therapy.
Abstract: MicroRNA-124 (miR-124), a pivotal member of the p53 network, was found to be down-regulated in multiple types of tumors and further reported as tumor suppressor microRNA In this study, we found that miR-124 was down-regulated in gastric cancer cell lines and specimens Restoration of miR-124 expression inhibited the proliferation and colony formation of gastric cancer cells EZH2 (enhancer of zeste homolog 2), which has been shown to be an important transcription factor involved in the proliferation and metastasis of tumor cells, was here confirmed to be a direct target gene of miR-124 On the other hand, silencing EZH2 also inhibits cell proliferation of gastric cancer cells Furthermore, the treatment combining miR-124 with 5-fluorouracil (5-FU) significantly showed more efficient anti-tumor effects than single treatment of miR-124 or 5-FU, and over-expression of miR-124 suppresses the tumor growth in vivo Our study indicate that miR-124 can suppress gastric cancer cell growth by directly targeting the EZH2 gene and sensitize the treatment effect of 5-FU Therefore, miR-124 shows tumor-suppressive activity and may be a new and useful approach of gastric cancer therapy

84 citations