Peste des petits ruminants virus (PPRV) causes highly contagious diseases in domestic and particular wild small ruminants, leading to substantial economic loss. The development of effective and cheap antiviral medications shall help to circumvent this emerging burden. In this study, we found that ribavirin, a competitive inosine-5’-monophosphate dehydrogenase (IMPDH) inhibitor, significantly inhibits the replication of PPRV. As IMPDH is a key enzyme in purine nucleotide synthesis, supplementation of exogenous guanosine attenuate the anti-PPRV effect of ribavirin. Interestingly, an uncompetitive IMPDH inhibitor, mycophenolic acid (MPA), exerted more potent antiviral effect again PPRV. Similarly, this effect was largely restored upon supplementation of guanosine. Thus, we have demonstrated that the IMPDH inhibitors ribavirin and MPA combat PPRV infection through purine nucleotide depletion. Because both regimens have been widely used in the clinic for treating viral infection or organ rejection in transplantation patients for decades, respectively, repurposing these existing safe and cheap medications may provide a new avenue for combating PPRV infection. 相似文献
1. There has been substantial research focused on the roles of microRNAs (miRNAs) and Piwi-interacting RNAs (piRNAs) derived from mammalian spermatozoa; however, comparatively little is known about the role of spermatozoa-derived miRNAs and piRNAs within breeding cockerels’ spermatozoa.
2. A small RNA library of cockerels’ spermatozoa was constructed using Illumina high-throughput sequencing technology. Unique sequences with lengths of 18–26 nucleotides were mapped to miRBase 21.0 and unique sequences with lengths of 25–37 nucleotides were mapped to a piRNA database. A total of 1311 miRNAs and 2448 potential piRNAs were identified. Based on stem-loop qRT-PCR, 8 miRNAs were validated.
3. Potential target genes of the abundant miRNAs were predicted, and further Kyoto Encyclopedia of Genes and Genomes database (KEGG) and Gene Ontology (GO) analyses were performed, which revealed that some candidate miRNAs were involved in the spermatogenesis process, spermatozoa epigenetic programming and further embryonic development.
5. GO and KEGG analyses based on mapping genes of expressed piRNAs were performed, which revealed that spermatozoal piRNAs could play important regulatory roles in embryonic development of offspring.
6. The search for endogenous spermatozoa miRNAs and piRNAs will contribute to a preliminary database for functional and molecular mechanistic studies in embryonic development and spermatozoa epigenetic programming. 相似文献
Liver metabolism is affected by nutrients. The aim of this study was to explore the effects of low‐protein diets (17% crude protein, CP) supplemented with branched‐chain amino acids (BCAAs), including leucine (Leu), isoleucine (Ile) and valine (Val), on hepatic amino acid profile and lipid metabolism in growing pigs. The ratio of Leu : Ile : Val in all groups was 1 : 0.51 : 0.63 (20% crude protein, CP), 1 : 1 : 1 (17% CP), 1 : 0.75 : 0.75 (17% CP), 1 : 0.51 : 0.63 (17% CP) and 1 : 0.25 : 0.25 (17% CP) respectively. Results revealed that compared to the positive control group (1 : 0.51 : 0.63, 20% CP), the low‐protein diets significantly augmented the concentrations of most essential amino acids and non‐essential amino acids (p <.05), with the greatest values observed in the 1 : 0.25 : 0.25 group. Moreover, relative to the control, the low‐protein diets with the Leu : Ile : Val ratio ranging from 1 : 0.75 : 0.75 to 1 : 0.25 : 0.25 markedly downregulated the mRNA abundance of acetyl‐CoA carboxylase (ACC), lipoprotein lipase (LPL) and fatty acid‐binding protein 4 (FABP‐4) (p <.05), and upregulated the mRNA expression of hormone‐sensitive lipase (HSL), peroxisome proliferator‐activated receptor‐g coactivator‐1α (PGC‐1α), uncoupling protein 3 (UCP3) and liver carnitine palmitoyltransferase 1 (L‐CPT‐1) (p <.05). Therefore, our data suggest that protein‐restricted diets supplemented with optimal BCAA ratio, that is, 1 : 0.75 : 0.75–1 : 0.25 : 0.25, induce a shift from fatty acid synthesis to fatty acid oxidation in the liver of growing pigs. These effects may be associated with increased mitochondrial biogenesis. 相似文献
This study evaluated the effects of dietary concentrate levels and 2‐methylbutyrate (2MB ) supplementation on performance, ruminal fermentation, bacteria abundance, microbial enzyme activity and urinary excretion of purine derivatives (PD ) in steers. Eight ruminally cannulated Simmental steers (12 months of age; 389 ± 3.7 kg of body weight) were used in a replicated 4 × 4 Latin square design with a 2 × 2 factorial arrangement. Moderate‐concentrate (400 g/kg diet [MC ]) or high‐concentrate (600 g/kg diet [HC ]) diets were fed with or without 2MB (0 g/day [2MB ?] or 15.0 g/day [2MB +]). Dry matter intake and average daily gain increased, but feed conversion ratio decreased with the HC diet or 2MB supplementation. Ruminal pH decreased, but total volatile fatty acid increased with the HC diet or 2MB supplementation. Molar proportion of acetate and acetate‐to‐propionate ratio decreased with the HC diet, but increased with 2MB supplementation. Propionate molar proportion and ruminal NH 3‐N content increased with the HC diet, but decreased with 2MB supplementation. Neutral detergent fibre degradability decreased with the HC diet, but increased with 2MB supplementation. Crude protein degradability increased with the HC diet or 2MB supplementation. Abundance of Ruminococcus albus , Ruminococcus flavefaciens , Fibrobacter succinogenes and Bufyrivibrio fibrisolvens as well as activities of carboxymethyl cellulase, cellobiase, xylanase and pectinase decreased with the HC diet, but increased with 2MB supplementation. However, abundance of Prevotella ruminicola and Ruminobacter amylophilus as well as activities of α‐amylase and protease increased with the HC diet or 2MB supplementation. Total PD excretion also increased with the HC diet or 2MB supplementation. The results suggested that growth performance, ruminal fermentation, CP degradability and total PD excretion increased with increasing dietary concentrate level from 40% to 60% or 2MB supplementation. The observed diet × 2MB interaction indicated that supplementation of 2MB was more efficacious for improving growth performance, ruminal fermentation and total PD excretion with promoted ruminal bacteria abundance and enzyme activity in the MC diet than in the HC diet. 相似文献
The aim of this study was to investigate the effects of excess leucine (Leu) vs. its metabolites α‐ketoisocaproate (KIC) and β‐hydroxy‐β‐methyl butyrate (HMB) on Leu metabolism, muscle fibre composition and muscle growth in growing pigs. Thirty‐two pigs with a similar initial weight (9.55 ± 0.19 kg) were fed 1 of 4 diets for 45 days: basal diet, basal diet + 1.25% L‐Leu, basal diet + 1.25% KIC‐Ca, basal diet + 0.62% HMB‐Ca. Results indicated that relative to the basal diet and HMB groups, Leu and KIC groups exhibited increased Leu concentrations and decreased concentrations of isoleucine, valine and EAAs in selected muscle (p <0.05) and had lower mRNA levels of MyHC I and higher expression of MyHC IIx/IIb (p <0.05), and there was no significant difference between the basal and HMB‐supplemented groups. Moreover, the mRNA expression levels of AMPKα and UCP3 were higher but the myostatin mRNA levels were lower in the soleus muscle of the HMB group than those from other groups (p <0.05). These findings demonstrated that doubling dietary Leu content exerted growth‐depressing effects in growing pigs; dietary KIC supplementation induced muscular branched‐chain amino acid imbalance and promoted muscle toward a more glycolytic phenotype; while dietary HMB supplementation promoted the generation of more oxidative muscle types and increased muscle growth specially in oxidative skeletal muscle, and these effects of HMB might be associated with the AMPKα‐Sirt1‐PGC‐1α axis and mitochondrial biogenesis. 相似文献
The purpose of this study was to investigate the effect of seminal plasma (SP) from bulls of known fertility on bovine endometrial epithelial cells (bEEC) in culture. The bEEC from passage 5, approximately 5.0–13 × 105 cells per flask, were challenged with SP from bulls of high or low fertility (n = 3 and 2, respectively) or PBS (control), at 1% (75 μl) or 4% (300 μl) and were incubated for 72 hr (n = 13 per challenge). Total cell number and viability of bEEC after challenge with 1% SP from either high‐ or low‐fertility bulls (75H or 75L, respectively) did not differ from controls. In contrast, challenge with 4% of SP from high‐ or low‐fertility bulls (300H or 300L) negatively affected bEEC cell number and viability. Challenge with 300 L had a greater adverse effect than 300H. These results suggest that the negative effect of bovine SP on bEEC is both dose‐dependent and fertility‐dependent. 相似文献