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Discussion on the role of DEHP in the critical period of gonadal development in pregnant rats (F0), studied the evolution of F1-F4 generation of inter-generational inheritance of cryptorchidism and the alteration of DNA methylation levels in testis. Pregnant SD rats were randomly divided into two groups: normal control group and DEHP experimental group. From pregnancy 7d to 19d, experimental group was sustained to gavage DEHP 750mg/kg bw/day, observed the incidence of cryptorchidism in offspring and examined the pregnancy rate of female rats through mating experiments. Continuous recording the rat’s weight and AGD value, after maturation (PND80) recording testis and epididymis’ size and weight, detected the sperm number and quality. Subsequently, we examined the evolution morphological changes of testicular tissue for 4 generation rats by HE staining and Western Blot. Completed the MeDIP-sequencing analysis of 6 samples (F1 generation, F4 generation and Control). DEHP successfully induced cryptorchidism occurrence in offspring during pregnancy. The incidence of cryptorchidism in F1 was 30%, in F2 was 12.5%, and there was no cryptorchidism coming up in F3 and F4. Mating experiment shows conception rate 50% in F1, F2 generation was 75%, the F3 and F4 generation were 100%. HE staining showed that the seminiferous epithelium of F1 generation was atrophy and with a few spermatogenic cell, F2 generation had improved, F3 and F4 generation were tend to be normal. The DNA methyltransferase expression was up-regulated with the increase of generations by Real Time-PCR, immunohistochemistry and Western Blot. MeDIP-seq Data Analysis Results show many differentially methylated DNA sequences between F1 and F4. DEHP damage male reproductive function in rats, affect expression of DNA methyltransferase enzyme, which in turn leads to genomic imprinting methylation pattern changes and passed on to the next generation, so that the offspring of male reproductive system critical role in the development of imprinted genes imbalances, and eventually lead to producing offspring cryptorchidism. This may be an important mechanism of reproductive system damage. [ABSTRACT FROM AUTHOR]

Oxidative stress is known as one of the main contributors in renal ischemia/reperfusion injury (IRI). Here we hypothesized that Micro-vesicles (MVs) derived from human Wharton Jelly mesenchymal stromal cells (hWJMSCs) could protect kidney against IRI through mitigating oxidative stress. MVs isolated from hWJMSCs conditioned medium were injected intravenously in rats immediately after unilateral kidney ischemia for 60 min. The animals were sacrificed at 24h, 48h and 2 weeks respectively after reperfusion. Our results show that the expression of NOX2 and reactive oxygen species (ROS) in injured kidney tissues was declined and the oxidative stress was alleviated in MVs group at 24h and 48h in parallel with the reduced apoptosis and enhanced proliferation of cells. IRI-initiated fibrosis was abrogated by MVs coincident with renal function amelioration at 2 weeks. NOX2 was also found down-regulated by MVs both in human umbilical vein endothelial cells (HUVEC) and NRK-52E cell line under hypoxia injury model in vitro. In conclusion, a single administration of hWJMSC-MVs might protect the kidney by alleviation of the oxidative stress in the early stage of kidney IRI through suppressing NOX2 expression. Moreover, it could reduce the fibrosis and improved renal function. [ABSTRACT FROM AUTHOR]

Background: The Macleaya spp., including Macleaya cordata and Macleaya microcarpa, are traditional anti-virus, inflammation eliminating, and insecticide herb medicines for their isoquinoline alkaloids. They are also known as the basis of the popular natural animal food addictive in Europe. However, few studies especially at genomics level were conducted on them. Hence, we performed the Macleaya spp. transcriptome and integrated it with iTRAQ proteome analysis in order to identify potential genes involved in alkaloids biosynthesis., Methodology and Principal Findings: We elaborately designed the transcriptome, proteome and metabolism profiling for 10 samples of both species to explore their alkaloids biosynthesis. From the transcriptome data, we obtained 69367 and 78255 unigenes for M. cordata and M. microcarpa, in which about two thirds of them were similar to sequences in public databases. By metabolism profiling, reverse patterns for alkaloids sanguinarine, chelerythrine, protopine, and allocryptopine were observed in different organs of two species. We characterized the expressions of enzymes in alkaloid biosynthesis pathways. We also identified more than 1000 proteins from iTRAQ proteome data. Our results strongly suggest that the root maybe the organ for major alkaloids biosynthesis of Macleaya spp. Except for biosynthesis, the alkaloids storage and transport were also important for their accumulation. The ultrastructure of laticifers by SEM helps us to prove the alkaloids maybe accumulated in the mature roots., Conclusions/significance: To our knowledge this is the first study to elucidate the genetic makeup of Macleaya spp. This work provides clues to the identification of the potential modulate genes involved in alkaloids biosynthesis in Macleaya spp., and sheds light on researches for non-model medicinal plants by integrating different high-throughput technologies.

Two forms of hepatitis B virus (HBV) C/D recombinant have been identified in western China, but little is known about their geographical and ethnic distributions, and particularly the clinical significance and specific mutations in the pre-core region. To address these questions, a total of 624 chronic HBV carriers from four ethnic populations representing five provinces in western China were enrolled in this study. Genotypes were firstly determined by restriction fragment length polymorphism, and then confirmed by full or partial genome nucleotide sequencing. The distribution of HBV genotypes was as follows: HBV/B: 40 (6.4%); HBV/C: 221 (35.4%); HBV/D: 39 (6.3%); HBV/CD: 324 (51.9%). In the 324 HBV C/D recombinant infections, 244 (75.3%) were infected with the "CD1" and 80 (24.7%) were infected with the "CD2." The distribution of HBV genotypes exhibited distinct patterns in different regions and ethnic populations. Geographically, the C/D recombinant was the most prevalent HBV strain on the Qinghai-Tibet Plateau. Ethnically, the C/D recombinant had a higher prevalence in Tibetan patients than in other populations. Clinically, patients with HBV/CD1 showed significantly lower levels of serum total bilirubin than patients with HBV/C2. The prevalence of HBeAg was comparable between patients with HBV/CD1 and HBV/C2 (63.3% vs 50.0%, P = 0.118) whether patients were taken together or stratified by age into three groups (65.6% vs 58.8% in <30 years, P = 0.758; 61.9% vs 48.0% in 30-50 years, P = 0.244; 64.3% vs 33.3%, P = 0.336). Virologically HBV/CD1 had a significantly lower frequency of G1896A than HBV/C2. In conclusion, the HBV C/D recombinant is restricted to the Qinghai-Tibet Plateau in western China and is found predominantly in Tibetans. The predominance of the premature pre-core stop mutation G1896A in patients with the HBV C/D recombinant may account for the higher prevalence of HBeAg in these patients.