Endogenous retrovirus HERVH-derived lncRNA UCA1 controls human trophoblast development.

Endogenous retroviruses (ERVs) are frequently reactivated in mammalian placenta. It has been proposed that ERVs contribute to shaping the gene regulatory network of mammalian trophoblasts, dominantly acting as species- and placental-specific enhancers. However, whether and how ERVs control human trophoblast development through alternative pathways remains poorly understood. Besides the well-recognized function of human endogenous retrovirus-H (HERVH) in maintaining pluripotency of early human epiblast, here we present a unique role of HERVH on trophoblast lineage development. We found that the LTR7C/HERVH subfamily exhibits an accessible chromatin state in the human trophoblast lineage. Particularly, the LTR7C/HERVH-derived Urothelial Cancer Associated 1 (UCA1), a primate-specific long non-coding RNA (lncRNA), is transcribed in human trophoblasts and promotes the proliferation of human trophoblast stem cells (hTSCs), whereas its ectopic expression compromises human trophoblast syncytialization coinciding with increased interferon signaling pathway. Importantly, UCA1 upregulation is detectable in placental samples from early-onset preeclampsia (EO-PE) patients and the transcriptome of EO-PE placenta exhibits considerable similarities to that of the syncytiotrophoblasts differentiated from UCA1-overexpressing hTSCs, supporting up-regulated UCA1 as a potential biomarker of this disease. Altogether, our data shed light on the versatile regulatory role of HERVH in early human development and provide a unique mechanism whereby ERVs exert a function in human placentation and placental syndromes.

Herbivore-induced tomato plant volatiles lead to the reduction of insecticides susceptibility in Spodoptera litura.

Herbivore-induced plant volatiles (HIPVs) have been associated with plant-plant-herbivorous-natural enemies communication and an enhanced response to the subsequent attack. Spodoptera litura is a serious cosmopolitan pest that has developed a high level of resistance to many insecticides. However, the underlying molecular and biochemical mechanism by which HIPV priming reduces S. litura larval sensitivity to insecticides remains largely unknown. This study was conducted to explore the potential of volatile from undamaged, or artificially damaged, or S. litura-damaged tomato plants on the susceptibility of S. litura to the insecticides beta-cypermethrin indoxacarb and chlorpyrifos. We found that larvae exposed to volatile from S. litura-damaged or artificially damaged tomato plants were significantly less susceptible to the three insecticides than those exposed to volatile from undamaged tomato plants. Elevated activities of detoxifying enzymes [cytochrome P450 monooxygenases (P450s), glutathione S-transferases (GSTs), and esterases (ESTs)], were expressed in S. litura larvae exposed to volatile from S. litura-damaged tomato plants than those exposed to volatile from undamaged tomato plants. Similarly, seven detoxification-related genes [GSTs (SlGSTe1, SlGSTo1, and SlGSTe3) and P450s (CYP6B48, CYP9A40, CYP321A7, and CYP321B1)] in the midgut and fat body of larvae were up-regulated under exposure to volatile from S. litura-damaged tomato plants. Increased volatile organic compounds emissions were detected in the headspace of tomato plants damaged by S. litura compared to the undamaged plants. Collectively, these findings suggest that HIPVs can considerably reduce caterpillar susceptibility to insecticides, possibly through induction-enhanced detoxification mechanisms, and provide valuable information for implementing an effective integrated pest management strategy.

Dynamic reprogramming of H3K9me3 at hominoid-specific retrotransposons during human preimplantation development.

Reprogramming of H3K9me3-dependent heterochromatin is required for early development. How H3K9me3 is involved in early human development remains, however, largely unclear. Here, we resolve the temporal landscape of H3K9me3 during human preimplantation development and its regulation for diverse hominoid-specific retrotransposons. At the 8-cell stage, H3K9me3 reprogramming at hominoid-specific retrotransposons termed SINE-VNTR-Alu (SVA) facilitates interaction between certain promoters and SVA-derived enhancers, promoting the zygotic genome activation. In trophectoderm, de novo H3K9me3 domains prevent pluripotent transcription factors from binding to hominoid-specific retrotransposons-derived regulatory elements for inner cell mass (ICM)-specific genes. H3K9me3 re-establishment at SVA elements in the ICM is associated with higher transcription of DNA repair genes, when compared with naive human pluripotent stem cells. Our data demonstrate that species-specific reorganization of H3K9me3-dependent heterochromatin at hominoid-specific retrotransposons plays important roles during early human development, shedding light on how the epigenetic regulation for early development has evolved in mammals.

Recapitulating early human development with 8C-like cells.

In human embryos, major zygotic genome activation (ZGA) initiates at the eight-cell (8C) stage. Abnormal ZGA leads to developmental defects and even contributes to the failure of human blastocyst formation or implantation. An in vitro cell model mimicking human 8C blastomeres would be invaluable to understanding the mechanisms regulating key biological events during early human development. Using the non-canonical promoter of LEUTX that putatively regulates human ZGA, we developed an 8C::mCherry reporter, which specifically marks the 8C state, to isolate rare 8C-like cells (8CLCs) from human preimplantation epiblast-like stem cells. The 8CLCs express a panel of human ZGA genes and have a unique transcriptome resembling that of the human 8C embryo. Using the 8C::mCherry reporter, we further optimize the chemical-based culture condition to increase and maintain the 8CLC population. Functionally, 8CLCs can self-organize to form blastocyst-like structures. The discovery and maintenance of 8CLCs provide an opportunity to recapitulate early human development.

Derivation of human triploid trophoblast stem cells.

PURPOSE: Human trophoblast stem cells (hTSCs) are counterparts of the precursor cells of the placenta and are valuable cell models for the study of placental development and the pathogenesis of placental diseases. The aim of this work was to establish a triploid human TSC (hTSC3PN) derived from the tripronuclear embryos, which are clinically discarded but readily available, for potential applications in basic placental research and disease modeling. METHODS: Eighteen tripronuclear human zygotes from IVF were collected and cultured for 5-6 days. Five high-quality blastocysts were harvested and were individually cultured in hTSC medium. Finally, two hTSC lines were established after 10 days and could be passaged stably. RESULTS: The karyotyping analysis showed that hTSC3PN contained three sets of chromosomes. And the hTSC3PN exhibited typical features of hTSCs, with the ability to differentiate into two trophoblast lineages: extravillous cytotrophoblasts (EVTs) and syncytiotrophoblasts (STs). In addition, the hTSC3PN can mimic some vital features of trophoblast, including hormone secretion and invasion. Further studies showed that the proliferation and differentiation of hTSC3PN were reduced compared with normal hTSCs, which may be related to the disturbed metabolic signaling in hTSC3PN. CONCLUSIONS: We established the triploid hTSC lines derived from tripronuclear embryos, which provides a potentially useful research model in vitro to study human placental biology and diseases.

miR-192/215-5p act as tumor suppressors and link Crohn's disease and colorectal cancer by targeting common metabolic pathways: An integrated informatics analysis and experimental study.

MicroRNAs have emerged as key regulators involved in a variety of biological processes. Previous studies have demonstrated that miR-192/215 participated in progression of Crohn's disease and colorectal cancer. However, their concrete relationships and regulation networks in diseases remain unclear. Here, we used bioinformatics methods to expound miR-192/215-5p macrocontrol regulatory networks shared by two diseases. For data mining and figure generation, several miRNA prediction tools, Human miRNA tissue atlas, FunRich, miRcancer, MalaCards, STRING, GEPIA, cBioPortal, GEO databases, Pathvisio, Graphpad Prism 6 software, etc . are extensively applied. miR-192/215-5p were specially distributed in colon tissues and enriched biological pathways were closely associated with human cancers. Emerging role of miR-192/215-5p and their common pathways in Crohn's disease and colorectal cancer was also analyzed. Based on results derived from multiple approaches, we identified the biological functions of miR-192/215-5p as a tumor suppressor and link Crohn's disease and colorectal cancer by targeting triglyceride synthesis and extracellular matrix remodeling pathways.

Incidental findings on brain MRI among Chinese at the age of 55-65 years: the Taizhou Imaging Study.

Asymptomatic brain abnormalities are common incidental findings on brain MRI in the elderly population and can be regarded as imaging markers of early stroke and dementia. We initiated the Taizhou Imaging Study (TIS) to examine the prevalence and correlates of incidental findings using brain MRI among an elderly population residing in a rural area of China. A total of 562 individuals, at the age of 55 to 65 years, participated in the TIS study with a response rate of 90%. The prevalence of lacunes, white matter hyperintensity (WMH), cerebral microbleeds (CMB), perivascular space, and intracranial arterial stenosis was 26.69%, 10.68%, 18.51%, 27.76%, and 12.81%, respectively. Age and hypertension were the major correlates of these incidental findings. Per each year increase in age, the risks of WMH and CMB increased by 15% and 14%. Compared to individuals with normal blood pressure, individuals with hypertension had an increased risk of all incidental findings, with the adjusted odds ratios of 2.28 to 5.45. Correlations of age, gender and body mass index with brain gray matter fraction were also observed. The high prevalence of these findings indicates a need of preventative strategy to help prevent future stroke and dementia in this population.

A homozygous MITF mutation leads to familial Waardenburg syndrome type 4.

Waardenburg syndrome (WS) is a genetic disorder characterized by hearing loss and pigmentary abnormalities with variable penetrance. Though heterozygous mutations in MITF are a major cause for Waardenburg syndrome type 2 (WS2), homozygous mutations in this gene and the associated phenotype have been rarely characterized. In this study, we identified a novel p.R223H mutation in MITF in a Chinese Han family with variable WS features. Both parents carried a heterozygous p.R223H mutation. They had normal hearing, and premature greying of the hair is their only pigmentary abnormality. In contrast, their two children both carried a homozygous p.R223H mutation and had classic WS features including profound hearing loss, heterochromia irides and marked pigmentary abnormalities in hair and skin. Interestingly, the two affected children also have persistent chronic constipation since the neonatal period, symptoms suggestive of Waardenburg syndrome type 4 (WS4). Our study revealed a likely association between homozygous mutations in MITF and WS4, which implies a dosage effect for the underlying pathogenesis mechanism.

Hsa-miR-34c suppresses growth and invasion of human laryngeal carcinoma cells via targeting c-Met.

MicroRNAs (miRNAs) are small noncoding RNA molecules that negatively modulate gene expression at the post-transcriptional level. A growing number of studies has shown that more and more miRNAs are aberrantly expressed and involved in the pathogenesis of several types of cancers. Here, we report that the down-regulated hsa-miR-34c was also involved in oncogenesis of laryngeal carcinoma. Our studies indicated that hsa-miR-34c functioned as a tumor suppressor which inhibited growth and invasion of human laryngeal carcinoma cells. Furthermore, in our study, an inverse relationship between the expression of hsa-miR-34c and c-Met was identified in 10 paired fresh samples from tumor tissues and adjacent normal tissues. Infection of hsa-miR-34c mediated by lentivirus suppressed the expression of c-Met directly. In addition, introduction of c-Met cDNA lacking 3'-UTR largely abrogated hsa-miR-34c-induced cell growth and invasion inhibition. These findings suggest aberrantly down-regulated hsa-miR-34c is a critical factor that contributes to malignancy in human laryngeal carcinoma by a mechanism involving targeting of c-Met.

[Effect of jieminqufeng decoction on cyclic nucleotides from the rats of allergic rhinitis].

OBJECTIVE: To observe the curative effect of Jieminqufeng decoction to the rats of allergic rhinitis and study the mechanism by which it treats allergic rhinitis. METHOD: Forty wistar rats were divided into 4 groups at random. There are Jieminqufeng decoction group, cetirizine group, model control group and normal control group. The rats of allergic rhinitis were established with ovalbumin. We surveyed the behavioral changes of rats, searched eosinophilic granulocytes in the nasal secretion, detected the contents of cAMP and cGMP in the blood plasma and nasal mucosa. RESULT: The model control group had typical symptoms of allergic rhinitis and the eosinophilic granulocytes could be found more frequently. The contents of cAMP and cAMP/cGMP rose in the blood plasma and nasal mucosa (P < 0.01). However, the changes of jieminqufeng decoction group were small. CONCLUSION: The jieminqufeng decoction is an effective drug to allergic rhinitis. Its possible mechanism is that it changes the contents of cAMP and cGMP, lessens inflammatory reaction and blocks up the allergy.