Drug-induced liver injury (DILI) is a widespread and harmful disease, and is closely linked to acute endoplasmic reticulum (ER) stress. Previous reports have shown that acute ER stress can suppress hepatic gluconeogenesis and even leads to hypoglycemia. However, the mechanism is still unclear. MAPK phosphatase 3 (MKP-3) is a positive regulator for gluconeogenesis. Thus, this study was conducted to investigate the role of MKP-3 in the suppression of gluconeogenesis by acute ER stress, as well as the regulatory role of acute ER stress on the expression of MKP-3. Results showed that acute ER stress induced by tunicamycin significantly suppressed gluconeogenesis in both hepatocytes and mouse liver, reduced glucose production level in hepatocytes, and decreased fasting blood glucose level in mice. Additionally, the protein level of MKP-3 was reduced by acute ER stress in both hepatocytes and mouse liver. Mkp-3 deficiency eliminated the inhibitory effect of acute ER stress on gluconeogenesis in hepatocytes. Moreover, the reduction effect of acute ER stress on blood glucose level and hepatic glucose 6-phosphatase (G6pc) expression was not observed in the liver-specific Mkp-3 knockout mice. Furthermore, activation of protein kinase R-like ER kinase (PERK) decreased the MKP-3 protein level, while inactivation of PERK abolished the reduction effect of acute ER stress on the MKP-3 protein level in hepatocytes. Taken together, our study suggested that acute ER stress could suppress hepatic gluconeogenesis by stimulating MKP-3 degradation via PERK, at least partially. Thus, MKP-3 might be a therapeutic target for DILI-related hypoglycemia.

Vitamin D3 (VD3) has been reported to improve the reproductive performance of sows. This study was conducted to investigate the long-term effect of maternal VD3 supplementation during gestation on the intestinal health of piglets. Twenty-three Landrace × Yorkshire gilts were randomly allocated into two groups to receive one of the following two diets during gestation: basal diet (CON group, 800 IU VD3 per kg diet, n = 12) and VD3 supplemented diet (VD3 group, 2000 IU VD3 per kg diet, n = 11). All sows were then fed with the same diet during lactation. Results showed that maternal VD3 supplementation during lactation tended to decrease (p = 0.08) the body weight loss of sows during lactation compared to the CON group. Besides, the relative length and weight of the small intestine (SI) and the villus height of the duodenum and ileum in weaning piglets were much higher (p < 0.05) in the VD3 group than those in the CON group, though their body weight was not changed. Meanwhile, maternal VD3 supplementation significantly upregulated the expression levels of IGF-1, IGF-2R, VDR, GLUT-2 and CAT1 in the duodenum (p < 0.05), and increased the expression levels of IGF-1, IGF-1R, IGF-2R, VDR, Occludin, ZO-1, MUC2, PEPT1 and CAT1 (p < 0.05) in the jejunum of suckling piglets compared with the CON group. Besides, the concentration of SigA in the jejunum of suckling piglets was higher (p < 0.05) in the VD3 group than that in the CON group. In addition, maternal VD3 supplementation significantly increased the contents of short chain fatty acids and the relative abundance of Lactobacillus and Faecalibacterium (p < 0.05) in the feces of weaning piglets compared to the CON group. Moreover, the relative abundance of unidentified_Lachnospiraceae in the feces of weaning piglets tended to be higher (p = 0.05), while that of unidentified_Spirochaetaceae was lower (p < 0.05) in the VD3 group than those in the CON group. Taken together, maternal VD3 supplementation during gestation could improve the intestinal function and microbiota in suckling piglets.

Vitamin E is generally believed to promote the production of ovine sperm mainly through its antioxidant effect. Our previous studies have shown that some non-antioxidant genes may also be key in mediating this process. The objective of this study was to identify key candidate proteins that were differentially expressed in response to a treatment with Vitamin E. Prepubertal ovine testicular cells were isolated and divided into two groups. They were either treated with 800 mu M Vitamin E (based on our previous results) or used as a non-treated control. After 24 h, all the cells were harvested for proteomic analysis. We found 115 differentially expressed proteins, 4 of which were up-regulated and 111 were down-regulated. A GO term enrichment analysis identified 127 Biological Process, 63 Cell Component and 26 Molecular Function terms that were enriched. Within those terms, 13, 11 and 26 terms were significantly enriched, respectively. Terms related to membrane and enzyme activity including the inner acrosomal membrane, signal peptidase complex, cysteine-type endopeptidase activity, etc., were also markedly enriched, while none of the KEGG pathways were enriched. We found that many of the differentially expressed proteins, such as CD46 (membrane cofactor protein), FLNA (Filamin A), DYSF (Dysferlin), IFT20 (Intraflagellar transport 20), SPCS1 (Signal peptidase complex subunit 1) and SPCS3 (Signal peptidase complex subunit 3) were related to the acrosomal and plasma membranes. A parallel reaction monitoring (PRM) analysis verified that Vitamin E improved spermatogenesis by regulating the expression of FLNA, SPCS3, YBX3 and RARS, proteins that are associated with the plasma membranes and protamine biosynthesis of the spermatozoa.

Vitamin E is known to improve testis development, yet the underlying mechanism responsible for this process remains poorly understood. To elucidate the mechanism, through which vitamin E facilitates testiscular development, we hypothesised that vitamin E improves testis development by promoting testis cell proliferation, while miRNAs also play a crucial role in the process. In order to test this hypothesis, we isolated primary testis cells from prepubertal sheep. Using the CCK-8 (Cell Counting Kit-8) assay we found that 800 mu M vitamin E supplementation enhanced cell proliferation. This was verified through western blot analysis of Ki67 and PCNA(proliferating cell nuclear antigen). Subsequently, cell cycle distribution induced by vitamin E was determined in the cells. Vitamin E markedly decreased the proportion of cells in the G1 phase and increased those in the S and G2/M phases in response to vitamin E supplementation. Meanwhile, vitamin E significantly increased expression of Cyclin B1 and Cyclin B3. Through the miRNAome and transcriptome technology, we identified a number of correlation pairs including miR-107-BLM (BLM RecQ like helicase), miR107-REL (REL proto-oncogene) and miR-493-3p-KLHL25 (kelch like family member 25), that are known to be involved in the regulation of correlation pairs participating in the cell cycle. Together these data demonstrate that 800 mu M vitamin E promotes testis cell proliferation and its action may be mediated by miR-107 and miR-493-3p that target the BLM, REL and KLHL25.

The effect of Vitamin E on the proliferation of ovine Sertoli cells was investigated. Sertoli cells were isolated and treated with various amounts of Vitamin E (0 mu M, 400 mu M, 800 mu M, 1000 mu M, 1200 mu M, 1400 mu M and 1600 mu M) for 24 h. We found that at the concentration of 1200 mu M, Vitamin E promoted Sertoli cell proliferation very effectively. It also increased the proportion of cells in the G1 phase while reduced that in the S and G2/M phases, suggesting that its effect on Sertoli cell proliferation is achieved by enhancing progression through the cell cycle. In addition, Vitamin E significantly up-regulated the transcript level of the PDPN, BMP6, AMPK alpha, GSK3 beta, Myc, and CDK6 genes and down-regulated that of PPAR gamma, Cyclin B1 and CDK4 as determined by qRT-PCR. Western blot analysis revealed that the expression of BMP6 and PDPN was also upregulated at the protein level, in accordance with the results of the qRT-PCR. Taken together, Vitamin E promoted Sertoli cell proliferation by affecting the expression of genes that regulate cell division and the cell cycle; this indicates that it can have a positive effect on sheep reproductive performance.

It is generally accepted that the phenotype and gene expression pattern of the offspring can be altered by maternal folic acid (FA) supplementation during the gestation period. The aims of this study were to investigate the effects of maternal FA supplementation on the growth performance, muscle development and immunity of newborn lambs of different litter size. According to litter size (twins, TW; triplets, TR) and maternal dietary FA supplementation levels (control, C; 16 or 32 mg·kg-1 FA supplementation, F16 and F32), neonatal lambs were randomly divided into six groups (TW-C, TW-F16, TW-F32, TR-C, TR-F16 and TR-F32). After farrowing, the birth weight in TW was higher than that in the TR group, and increased with FA supplementation of their mothers (P<.05). Folate, IGF-I, IgM and IgA concentrations of newborn lambs showed a litter size and FA supplementation interaction (P<.05). FA supplementation also increased diameter, area, perimeter and DNA content of the longissimus dorsi muscle of the lambs (P<.05) regardless of the litter size. Transcriptome analysis of the longissimus dorsi muscle revealed differentially expressed genes with dietary FA supplementation enriched in immunity- and cell development-related genes. Furthermore, FA supplementation upregulated the expression of myogenesis-related genes, while downregulated those involved in the inhibition of muscle development. In addition, immunity-related genes in the neonatal lambs showed lower expression levels in response to maternal dietary FA supplementation. Overall, maternal FA supplementation during gestation could increase the offspring's birth weight and modulate its muscle development and immunity.

睾丸内细胞类群较多,研究多集中于间质细胞、支持细胞以及生殖细胞.3种细胞虽功能不同,但最终都可影响精子的发生.miRNA大约22 nt,广泛分布于3种细胞内,并对细胞功能起到重要的调控作用.本文综述了miRNAs对睾丸内间质细胞、支持细胞以及生殖细胞的功能调控作用.miRNAs可以通过抑制下游靶基因,影响间质细胞的数量及睾酮合成、调控支持细胞的增殖和凋亡以及生殖细胞的细胞周期、凋亡和染色质重塑.

本文主要综述了维生素E对于羊肉品质的调控及其作用机理.维生素E作为一种脂溶性抗氧剂,不仅可以延缓羊肉脂质氧化,保持肉色,还能改变脂肪酸组成.维生素E的抗氧化性和对脂类代谢相关基因的调控在一定程度上解释维生素E对羊肉品质的调控机理.

We created a cDNA microarray representing approximately 3,500 pig genes for functional genomic studies. The array elements were selected from 6,494 cDNA clones identified in a large-scale expressed sequence tag (EST) project. These cDNA clones came from normalized and subtracted porcine adipose tissue cDNA libraries. Sequence similarity searches of the 3,426 ESTs represented on the array using BLASTN identified 2,790 (81.4%) as putative human orthologs, with the remainder consisting of "novel" genes or highly divergent orthologs. We used the gene microarray to profile transcripts expressed by adipose tissue of fatty Chinese Xiang pig (XP) and muscley Large White (LW). Microarray analysis of RNA extracted from adipose tissue of fatty XP and muscley LW identified 81 genes that were differently expressed two fold or more. Transcriptional differences of four of these genes, adipocyte fatty acid binding protein (aP2), stearyl-CoA desaturase (SCD), sterol regulatory element binding transcription factor 1 (SREBF1) and lipoprotein lipase (LPL) were confirmed using SYBR Green quantitative RT-PCR technology. Our results showed that high expression of SCD and SREBF1 may be one of the reasons that larger fat deposits are observed in the XP. In addition, our findings also illustrate the potential power of microarrays for understanding the molecular mechanisms of porcine development, disease resistance, nutrition, fertility and production traits.