Biology subjects

Zhong, M.

Publications and source records attributed to Zhong, M..

43 records · Page 3Linked to original sources

bioRxiv2019

Placental Editome Profiling Reveals Widespread RNA-Editing Dysregulation in Preeclampsia

Dysregulated RNA editing is well documented in several diseases such as cancer. The extent to which RNA editing might be involved in diseases originated in the placenta remains unknown, because RNA editing has rarely been studied in the placenta. Here, we have systematically profiled RNA editome on the placentae from 9 patients with early-onset severe preeclampsia (EOSPE) and 32 normal subjects, and a widespread RNA editing dysregulation in EOSPE has been identified. The mis-edited gene set is enriched with known preeclampsia-associated genes and differentially expressed genes in EOSPE. The \"RNA editing events\" at two microRNA binding sites in 3-UTR of the LEP mRNA were generated, which could lead to increased expression level of LEP in trophoblast cells. Upregulation of LEP were also observed in the placentae of PE patients. These results suggest that widespread placental RNA editing may be involved in placental development and dysregulation of RNA editing in the placenta may contribute to the pathogenesis of preeclampsia.

genomics↗

bioRxiv2019

Distinct molecular processes in placentae involved in two major subtypes of preeclampsia

Patients with preeclampsia display a spectrum of onset time and severity of clinical presentation, yet the underlying molecular bases for the early-onset and late-onset clinical subtypes are not known. Since the root cause of PE is thought to be located in the placentae, we carried out RNA-seq on 65 high-quality placenta samples, including 33 from 30 patients and 32 from 30 control subjects, to search for molecular features. We identified two functionally distinct sets of dysregulated genes in two major subtypes: metabolism-related genes, notably transporter genes, in early-onset severe preeclampsia and immune-related genes in late-onset severe preeclampsia, while the late-onset mild preeclampsia could not be distinguished from normal controls. A small number of dysregulated transcription factors may drive the widespread gene dysregulation in both early-onset and late-onset patients. These results suggest that early-onset and late-onset severe preeclampsia have different molecular mechanisms, whereas the late-onset mild preeclampsia may have no placenta-specific causal factors.

genomics↗

bioRxiv2019

Detection of EGFR deletion using unique RepSeq technology

We are reporting a novel sequencing technology, RepSeq (Repetitive Sequence), that has high sensitivity, specificity and quick turn-around time. This new sequencing technology is developed by modifying traditional Sanger sequencing technology in several aspects. The first, a homopolymer tail is added to the PCR primer(s), which makes interpreting electropherograms a lot easier than that in traditional Sanger sequencing. The second, an indicator nucleotide is added at the 5end of the homopolymer tail. In the presence of a deletion, the position of the indicator nucleotide in relation to the wild type confirms the deletion. At the same time, the indicator of the wild type serves as the internal control. Furthermore, the specific design of the PCR and/or sequencing primers will specifically enrich/select mutant alleles, which increases sensitivity and specificity significantly. Based on serial dilution studies, the analytical lower limit of detection was 1.47 copies. A total of 89 samples were tested for EGFR exon 19 deletion, of which 21 were normal blood samples and 68 were samples previously tested by either pyrosequencing or TruSeq Next Generation Sequencing Cancer Panel. There was 100 % concordance among all the samples tested. RepSeq technology has overcome the shortcomings of Sanger sequencing and offers an easy-to-use novel sequencing method for personalized precision medicine.

genomics↗

bioRxiv2019

LncRNA Dnmt3aos regulates Dnmt3a expression leading to aberrant DNA methylation in macrophage polarization

Long non-coding RNAs (lncRNAs) play key roles in various biological processes. However, the roles of lncRNAs in macrophage polarization remain largely unexplored. In this study, thousands of lncRNAs were identified that are differentially expressed in distinct polarized bone marrow-derived macrophages (BMDMs). Among them, Dnmt3aos (DNA methyltransferase 3A, opposite strand), as a known lncRNA, locates on the antisense strand of Dnmt3a. Functional experiments further confirmed that Dnmt3aos were highly expressed in M(IL-4) macrophages and participated in the regulation of Dnmt3a expression, and played a key role in macrophage polarization. The DNA methylation profiles between the Dnmt3aos knockdown group and the control group in M(IL-4) macrophages were determined by MeDIP-seq technique for the first time, and the Dnmt3aos-Dnmt3a axis-mediated DNA methylation modification-regulated macrophage polarization related gene IFN-{gamma} was identified. Our study will help to enrich our knowledge of the mechanism of macrophage polarization and will provide new insights for immunotherapy in macrophage-associated diseases.

cell biology↗

bioRxiv2018

MLL-AF9 Initiates Transformation From Fast-Proliferating Myeloid Progenitors

Cancer is a hyper-proliferative clonal disease. Whether the proliferative state originates from the cell-of-origin or emerges later remains elusive. By tracking de novo transformation from normal hematopoietic progenitors expressing an acute myeloid leukemia (AML) oncogene MLL-AF9, we reveal that the cell cycle rate heterogeneity among granulocyte-macrophage progenitors (GMPs) determines their probability of transformation. An intrinsic fast cell cycle kinetics at the time of oncogene expression provide permissiveness for transformation, with the fastest cycling 3% of GMPs ([~]0.006% of bone marrow nucleated cells) acquiring malignancy with nearly 100% efficiency. Molecularly, we propose that MLL-AF9 preserves the gene expression of the cellular states in which it is expressed. As such, when expressed in the naturally-existing, rapidly-cycling myeloid progenitors, this cell state is perpetuated, yielding malignancy. Our work elucidates one of the earliest steps toward malignancy and suggests that modifying the cycling state of the cell-of-origin could be an effective approach to prevent malignancy.

cancer biology↗

bioRxiv2018

PLOS ONETitle - Optimization of the flash extraction of flavonoids from the leaves of Salix babylonica using the response surface method and an evaluation of the leaves high antioxidant activity

Many biological activities of Salix babylonica leaves are attributed to the plants high total flavonoid content. Flash extraction has the advantages of high efficiency and maximum retention of the active ingredient. In this study, flash extraction was used to extract the total flavonoids, and a Box-Behnken design was used to optimize the extraction conditions for the first time. The effects of four independent variables, including ethanol concentration, extraction voltage, time, and ratio of liquid to material on flavonoid yield, was determined, and the optimal conditions for flavonoid extraction were evaluated using response surface methodology. Statistical analyses showed that the linear and quadratic terms of these four variables had significant effects. The fitted second-order model revealed that the optimal conditions consisted of an ethanol concentration of 67.91%, extraction time of 87 s, extraction voltage of 116 V and ratio of liquid to material of 42.79. Under the optimum conditions, the experimental value of 66.40{+/-}0.80% nearly coincided with that predicted by the model. In the ferric reducing antioxidant power (FRAP) and 2,2-diphenyl-1-picrylhydrazyl radical (DPPH.) assays, the extracts showed significant antioxidant and scavenging capacity for free radicals, respectively. This study helps to better exploit the resources of Salix babylonica leaves and provides new insights for effective extraction of flavonoids.

pharmacology and toxicology↗

bioRxiv2017

De novo assemblies of high-quality reference transcriptomes identifies Rosaceae-common and Rosa-specific encoding genes

Roses are important plants for human beings with important economical and biological traits like continuous flowering, flower architecture, color and scent, that current model plants do not feature, thus are becoming ideal models for studying these traits. Due to high heterozygosity of rose genomes likely caused by frequent inter-species hybridization, a high-quality and well-annotated genome for Rosa plants is not available yet. Developing genetic and genomic tools with high quality has become necessary for further roses breeding and for disentangling the molecular genetic mechanisms underlying roses domestication. We here generated the high quality and comprehensive reference transcriptomes for Rosa chinensis Old Blush (OB) and R. wichuriana Basyes Thornless (BT), two roses contrasting at several important traits. These reference transcriptomes showed transcripts N50 above 2000bp. The two species shared about 23310 transcripts (N50 = 2364bp), among which about 8975 orthologs were conserved within genera of Rosa. Rosa plants shared about 5049 transcripts (Rosaceae-common) with these from Malus, Prunus, Rubus, and Fragaria. Finally, a pool of 417 transcripts unique to Rosa plants (Rosa-specific) was identified. These Rosaceae-common and Rosa-specific transcripts should facilitate the phylogenetic analysis of Rosaceae plants and investigation of Rosa-specific traits. The data reported here should provide the fundamental genomic tools and knowledge critical for understanding the biology and domestication of roses.

plant biology↗