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(1) Background: the current research was conducted to investigate the potential non-antioxidant roles of vitamin E in the protection of hepatocysts from oxidative damage. (2) Methods: primary sheep hepatocytes were cultured and exposed to 200, 400, 600, or 800 μmol/L hydrogen peroxide, while their viability was assessed using a CCK-8 kit. Then, cells were treated with 400 μmol/L hydrogen peroxide following a pretreatment with 50, 100, 200, 400, and 800 μmol/L vitamin E and their intracellular ROS levels were determined by means of the DCF-DA assay. RNA-seq, verified by qRT-PCR, was conducted thereafter: non-treated control (C1); cells treated with 400 μmol/L hydrogen peroxide (C2); and C2 plus a pretreatment with 100 μmol/L vitamin E (T1). (3) Results: the 200-800 μmol/L hydrogen peroxide caused significant cell death, while 50, 100, and 200 μmol/L vitamin E pretreatment significantly improved the survival rate of hepatocytes. ROS content in the cells pretreated with vitamin E was significantly lower than that in the control group and hydrogen-peroxide-treated group, especially in those pretreated with 100 μmol/L vitamin E. The differentially expressed genes (DEGs) concerning cell death involved in apoptosis ( RIPK1 , TLR7 , CASP8 , and CASP8AP2 ), pyroptosis ( NLRP3 , IL-1β , and IRAK2 ), and ferroptosis ( TFRC and PTGS2 ). The abundances of IL-1β , IRAK2 , NLRP3 , CASP8 , CASP8AP2 , RIPK1 , and TLR7 were significantly increased in the C1 group and decreased in T1 group, while TFRC and PTGS2 were increased in T1 group. (4) Conclusions: oxidative stress induced by hydrogen peroxide caused cellular damage and death in sheep hepatocytes. Pretreatment with vitamin E effectively reduced intracellular ROS levels and protected the hepatocytes from cell death by regulating gene expression associated with apoptosis ( RIPK1 , TLR7 , CASP8 , and CASP8AP2) and pyroptosis ( NLRP3 , IL-1β , and IRAK2 ), but not ferroptosis ( TFRC and PTGS2) .

Maternal folic acid (FA) plays an important role in the fetus development, but it is unknown the response of hepatic metabolism in the offspring from different litter sizes to maternal FA supplementation. In the present study, this was done by feeding the ewes with 0, 16 and 32 mg/(kg·DM) FA supplemented diet during pregnancy and analysing the hepatic one-carbon metabolism-related indices and gene expression in the neonatal lambs of different litter sizes (twins, TW; triplets, TR). Regardless of litter sizes, the concentrations of folate, methionine, S-adenosylmethionine and DNA methyltransferase increased significantly, but homocysteine and S-adenosylhomocysteine decreased in the liver of newborn lambs from ewes whose diet was supplemented with FA. In TW, maternal FA status has little effect on hepatic genes expression profile of newborn lambs, and no significant enriched pathway was found. However, DEG involved in cell proliferation such as CCNA2, CCNB2, CCNE2, CDK1 and BUB1 were significantly enriched when the ewes were supplemented with FA in TR groups. In addition, nucleotide synthesis-related genes such as POLD1, POLD2, MCM4 and MCM5 were enriched markedly in DNA replication and pyrimidine metabolism pathways in triplets when a higher FA ingestion [32 mg/(kg·DM)] was implemented in ewes. This finding demonstrated that the hepatic methyl metabolism in TW and TR newborn lambs was regulated by maternal FA status. The hepatic cell proliferation and nucleotide metabolism related genes in TR were more susceptible to maternal dietary FA supplementation during pregnancy. [ABSTRACT FROM AUTHOR]

LINC01355 has been demonstrated to be dysregulated in several cancers. However, the exact molecular function of LINC01355 in the pathogenesis of OSCC remains unstudied. Here, we reported the effect of LINC01355 in OSCC and investigated the mechanisms. Firstly, we found that the results indicated LINC01355 was increased in OSCC cells. Knockdown of LINC01355 repressed OSCC cell proliferation, migration, and invasion. Recently, immunotherapy is a significant method for the treatment of cancers, in which CD8+ T cells exhibit a significant role. The influence of LINC01355 on the antitumor activity of CD8+ T cells was also focused in this study. As shown, the silence of LINC01355 could repress OSCC tumor growth via inducing CD8+ T cell immune responses. In addition, we found that downregulation of LINC01355 significantly restrained CD8+ T cell apoptosis, induced CD8+ T cell percentage, and enhanced the cytolysis activity when cocultured with OSCC cells. It has been reported that the Notch pathway represses CD8+ T cell activity in cancer patients. In our present study, we displayed that lack of LINC01355 suppressed OSCC malignant behaviors and enhanced the antitumor activity of CD8+ T cells via inactivating Notch signaling. We showed that decreased LINC01355 significantly restrained the Notch signal via a decrease of Notch-1, JAG-1, and HES-1. Repression of Notch1 reversed the effect of LINC01355 in OSCC cells. In conclusion, it was implied that LINC01355 might induce the development of OSCC via modulating the Notch signal pathway, which could provide a candidate therapeutic target for OSCC. [ABSTRACT FROM AUTHOR]

The formation mechanism of volatile compounds in Tan lamb meat under different feeding regimes remains unclear. This study aimed to determine whether the volatile compounds in meat are related to lipid metabolism in an attempt to improve the theoretical basis for increasing the yield and quality of lamb production. Results showed that the specialized pasture grazing with indoor feeding (GF) and indoor feeding only (F) regimes had advantages in terms of growth and carcass traits compared to the specialized pasture grazing only (G) regime. Lamb meat qualities of the GF group were in an intergrade position compared to those of the F and G groups. Although the lamb meat of the three groups had different aroma attributes, as measured using SPME-GC-MS, GF lamb meat had the most pleasant active compounds. In contrast, the expression of lipid transport genes was altered in all three groups. In summary, Tan lambs had different growth performance, intramuscular fat content, and composition under the three feeding regimes, which might be due to the differences in energy and lipid transport, resulting in unique volatile compound profiles in meat from different groups. [ABSTRACT FROM AUTHOR]

Background: Litter size affects fetal development but its relation to diet-induced fatty liver later in life is unknown.Objectives: This aim of this study was to test the hypothesis that litter size influences postweaning fatty liver development in response to soybean oil-supplemented diet.Methods: Weanling twin (TW) or triplet (TP) male lambs (n = 16) were fed a control diet or 2% soybean oil-supplemented diet (SO) for 90 d. Liver tissue morphology, biochemical parameters, and lipid metabolic enzymes were determined. Hepatic gene expression was analyzed by RNA sequencing (n = 3), followed by enrichment analysis according to Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes. Differentially expressed genes involved in lipid metabolism were further verified by quantitative reverse transcriptase-polymerase chain reaction (n = 4). All data were analyzed by a 2-factor ANOVA, apart from differentially expressed genes, which were identified by the Benjamini-Hochberg approach (q value ≤0.05).Results: SO increased liver triglyceride (by 55%) and nonesterified fatty acid (by 54%) concentrations in TPs (P ≤ 0.05) but not in TWs (P > 0.05). SO also induced a 2.3- and 2.1-fold increase in the liver steatosis score of TPs and TWs, respectively (P ≤ 0.05). Moreover, SO reduced the activity of lipolytic enzymes including hepatic lipase and total lipase in TPs by 47% and 25%, respectively (P ≤ 0.05). In contrast, activities of lipogenic enzymes, including malic enzyme and acetyl coenzyme A carboxylase, were significantly higher in TPs (P ≤ 0.05). Moreover, TPs had higher expression of lipogenic genes, such as FASN (by 45%) and APOB (by 72%), and lower expression of lipolytic genes, such as PRKAA2 (by 28%) and CPT1A (by 43%), compared with TWs (P ≤ 0.05).Conclusions: TPs have a gene expression profile that is more susceptible to SO-induced fatty liver than that of TWs, which indicates that insufficient maternal nutrient supply at fetal and neonatal stages may increase the risk of nonalcoholic fatty liver disease. [ABSTRACT FROM AUTHOR]

The effects of the different feeding systems, graze feeding (GSF), time-limited graze feeding (GF), and stall-feeding (SF)) on the fatty acid content, metabolites, and genes expression of the longissimus dorsi (LD) in Tan lambs were investigated in the present study. Thirty-nine 4-month-old male Tan lambs with similar body weight (24.91 ± 1.74 kg) were selected and divided into the three feeding systems (n = 13) randomly. Lambs were slaughtered after 83 days of the feeding trails, and LD muscle samples were collected for further analysis. The results indicated that different feeding systems have no significant effect on short-chain fatty acids in Tan lambs (p > 0.05). However, the total saturated fatty acids (∑SFA) and monounsaturated fatty acids (∑MUFA) in the GSF and GF groups were lower than those in the SF group (p < 0.001). The total polyunsaturated fatty acids (∑PUFA) in the GSF group were higher than those in the GF and SF groups (p < 0.001). Moreover, in the comparison of both GF vs GSF groups and SF vs GSF groups, metabolomic analysis showed that metabolites such as cis-(6,9,12)-linolenic acid, arachidic acid, acetylcarnitine, and L-carnitine with lower concentration were significantly enriched in the biosynthesis of unsaturated fatty acid pathway (p < 0.05), but metabolites such as phosphorylcholine, glycerophosphocholine, cytidine 5'-diphosphocholine, and glycerol-3-phosphate with higher concentrations were enriched in the glycerophospholipid metabolism pathway. KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis of the results indicated that in the comparison of the GSF group with the SF group, differentially expressed genes (DEGs) such as LIPC, ERFE, FABP3, PLA2R1, LDLR, and SLC10A6, were enriched in the steroid biosynthesis and cholesterol metabolism pathways. In addition, differential metabolites and genes showed a significant correlation with the content of ∑SFA, ∑MUFA, and ∑PUFA in lamb meat (p < 0.05). These findings demonstrated that the feeding system was an important factor in regulating fatty acid content by affecting lipid-metabolism-related metabolites and gene expression in muscle, and graze-feeding system provided lamb meat with higher ∑PUFA content than time-limited-grazing and stall-feeding systems. [ABSTRACT FROM AUTHOR]

Simple Summary: Maternal folic acid (FA) level during gestation is a factor affecting fetal development due to the vital role of FA in nucleotide synthesis. As a key organ of lamb, the development of the small intestine during gestation in response to maternal FA is not clear. Therefore, the current study evaluated the intestinal phenotype and development-, apoptosis- and digestion-related genes expression in newborn lambs whose mothers supplemented FA during gestation. FA supplementation improved the ratio of small intestinal weight to live body weight, intestinal muscle layer thickness and the expression of IGF-I, BCL-2 and SGLT1. Meanwhile, triplets indicated poorer morphological development compared to twins, but the expression of several genes was higher in twins compared to triplets. Overall, maternal FA supplementation during gestation increased the development of offspring's small intestinal. The purpose of this study was to investigate the effect of maternal dietary folic acid (FA) supplementation during gestation on small intestinal development of newborn lambs of different litter sizes, focusing on the intestinal morphology and development-, apoptosis- and digestion-related genes expression. One hundred and twenty Hu ewes (Ovis aries) were inseminated and randomly allotted to three groups. One group received a control diet [without FA supplementation, control (CON)] and the other two groups received control diets supplemented with different amount of FA [16 or 32 mg FA per kg dry matter (DM), i.e., F16 and F32] during pregnancy. After lambing, according to the dietary FA levels and litter size (twins, TW; triplets, TR), the neonatal lambs were divided into 6 (TW-CON, TW-F16, TW-F32, TR-CON, TR-F16, TR-F32) treatment groups. The results showed that the ratio of small intestinal weight to live body weight and the thickness of the intestinal muscle layer in the offspring was enhanced significantly with increasing maternal FA supplementation (p < 0.05). Meanwhile, the expression levels of insulin-like growth factor I (IGF-I), B-cell lymphoma-2 (BCL-2) and sodium/glucose co-transporter-1 (SGLT1) in the small intestines of the newborn lambs were increased, while the opposite was true for Bcl2-associated × (BAX) in response to FA supplementation (p < 0.05). Moreover, the small intestinal weights of twins were significantly higher than those of triplets (p < 0.01), and the expression levels of IGF-I (p < 0.05), sucrase-isomaltase (SI) (p < 0.05) and solute carrier family 2 member 5 (SLC2A5) (p < 0.01) were significantly lower than those in triplets. These findings suggest that maternal FA supplementation could improve the offspring's small intestinal phenotype and the expression of development-, apoptosis- and digestion-related genes, so it could promote the small intestinal development of newborn lambs. Furthermore, the small intestine phenotypic development of twins was generally better than that of triplets, while the expression levels of the above genes of twins were lower than those of triplets. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Gene-chip technology was employed to study the effect of dietary vitamin E on gene expression in sheep testes based on our previous research. Thirty-five male Tan sheep (20–30 days after weaning) with similar body weight were randomly allocated into five groups and supplemented 0, 20, 100, 200 and 2000 IU sheep − 1 day − 1 vitamin E (treatments denoted as E0, E20, E100, E200, and E2000, respectively) for 120 days. At the end of the study the sheep were slaughtered and the testis samples were immediately collected and stored in liquid nitrogen. Differences in gene expression between different treated groups were identified. Based on GO enrichment analysis and the KEGG database to evaluate the gene expression data we found that vitamin E might affect genes in the testes by modulating the oxidation level, by affecting the expression of various receptors and transcription factors in biological pathways, and by regulating the expression of metabolism-associated genes. The effect of vitamin E supplementation on the expression of oxidative enzyme-related genes was detected by quantitative real-time PCR (qRT-PCR) and Western blot. The results show that dietary vitamin E, at various doses, can significantly increase ( P < 0.05) the mRNA and protein expression of Glutathione peroxidase 3 and Glutathione S-transferase alpha 1. In addition, the results of qRT-PCR of the antioxidant enzyme genes were consistent with those obtained using the gene chip microarray analysis. In summary, the dietary vitamin E treatment altered the expression of a number of genes in sheep testes. The increase in the mRNA and protein levels of antioxidant enzyme genes, coupled with the elevation in the activity of the antioxidant enzymes were primarily responsible for the improved reproductive performance promoted by dietary vitamin E. [ABSTRACT FROM AUTHOR]