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Agriculture ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. 105
Author(s):  
Minmeng Zhao ◽  
Kang Wen ◽  
Xiang Fan ◽  
Qingyun Sun ◽  
Diego Jauregui ◽  
...  

OTU deubiquitinase 7A (OTUD7A) can suppress inflammation signaling pathways, but it is unclear whether the gene can inhibit inflammation in goose fatty liver. In order to investigate the functions of OTUD7A and identify the genes and pathways subjected to the regulation of OTUD7A in the formation of goose fatty liver, we conducted transcriptomic analysis of cells, which revealed several genes related to inflammation and immunity that were significantly differentially expressed after OTUD7A overexpression. Moreover, the expression of interferon-induced protein with tetratricopeptide repeats 5 (IFIT5), tumor necrosis factor ligand superfamily member 8 (TNFSF8), sterile alpha motif domain-containing protein 9 (SAMD9), radical S-adenosyl methionine domain-containing protein 2 (RSAD2), interferon-induced GTP-binding protein Mx1 (MX1), and interferon-induced guanylate binding protein 1-like (GBP1) was inhibited by OTUD7A overexpression but induced by OTUD7A knockdown with small interfering RNA in goose hepatocytes. Furthermore, the mRNA expression of IFIT5, TNFSF8, SAMD9, RSAD2, MX1, and GBP1 was downregulated, whereas OTUD7A expression was upregulated in goose fatty liver after 12 days of overfeeding. In contrast, the expression patterns of these genes showed nearly the opposite trend after 24 days of overfeeding. Taken together, these findings indicate that OTUD7A regulates the expression of inflammation- and immune-related genes in the development of goose fatty liver.


2022 ◽  
Author(s):  
Liubov Gapa ◽  
Huda Alfardus ◽  
Wolfgang Fischle

Chromatin, the complex of DNA and histone proteins, serves as a main integrator of cellular signals. Increasing evidence links cellular functional to chromatin state. Indeed, different metabolites are emerging as modulators of chromatin function and structure. Alterations in chromatin state are decisive for regulating all aspects of genome function and ultimately have the potential to produce phenotypic changes. Several metabolites such as acetyl-CoA, S-adenosyl methionine (SAM) or adenosine triphosphate (ATP) have now been well characterized as main substrates or cofactors of chromatin modifying enzymes. However, there are other metabolites that can directly interact with chromatin influencing its state or that modulate the properties of chromatin regulatory factors. Also, there is a growing list of atypical enzymatic and non-enzymatic chromatin modifications that originate from different cellular pathways that have not been in the limelight of chromatin research. Here, we summarize different properties and functions of uncommon regulatory molecules originating from intermediate metabolism of lipids, carbohydrates and amino acids. Based on the various modes of action on chromatin and the plethora of putative, so far not described chromatin regulating metabolites, we propose that there are more links between cellular functional state and chromatin regulation to be discovered. We hypothesize that these connections could provide interesting starting points for interfering with cellular epigenetic states at a molecular level.


2022 ◽  
Vol 951 (1) ◽  
pp. 012030
Author(s):  
Y Hardiyanto ◽  
A Jayanegara ◽  
R Mutia ◽  
S Nofyangtri

Abstract Guanidinoacetic acid (GAA) is formed by the arginine and glycine that are catalysed by arginine:glycine amidinotransferase in the kidney. In the liver, GAA is methylated by s-adenosyl methionine and converted to creatine, then deposited into muscle as energy supply. This meta-analysis was done by integrating 20 articles from various journals. Supplementation doses ranged from 0 to 8000 ppm/kg feed. The mixed model methodology was employed with GAA level and broiler strain as fixed effects and studies as random effects. The results showed that increasing GAA level improved average daily gain day 0-21 and reduced feed conversion ratio day 0-35 (P<0.05). A higher GAA also accompanied by decreasing relative liver weight (P<0.05). GAA supplementation did not affect average daily feed intake and percentage of carcass traits (carcass, legs, breast, wings, drum, thigh) and other parameters such as abdominal fat, gizzard, heart, bursa, thymus and spleen (P>0.05). It was concluded that supplementation of GAA improved the performance of broilers.


2021 ◽  
Vol 22 (24) ◽  
pp. 13593
Author(s):  
Baiba Brūmele ◽  
Margit Mutso ◽  
Lilian Telanne ◽  
Kadri Õunap ◽  
Karīna Spunde ◽  
...  

Methylation is an essential epigenetic modification mainly catalysed by S-Adenosyl methionine-dependent methyltransferases (MTases). Several MTases require a cofactor for their metabolic stability and enzymatic activity. TRMT112 is a small evolutionary conserved protein that acts as a co-factor and activator for different MTases involved in rRNA, tRNA and protein methylation. Using a SILAC screen, we pulled down seven methyltransferases—N6AMT1, WBSCR22, METTL5, ALKBH8, THUMPD2, THUMPD3 and TRMT11—as interaction partners of TRMT112. We showed that TRMT112 stabilises all seven MTases in cells. TRMT112 and MTases exhibit a strong mutual feedback loop when expressed together in cells. TRMT112 interacts with its partners in a similar way; however, single amino acid mutations on the surface of TRMT112 reveal several differences as well. In summary, mammalian TRMT112 can be considered as a central “hub” protein that regulates the activity of at least seven methyltransferases.


2021 ◽  
Vol 17 (12) ◽  
pp. e1009708
Author(s):  
Ruby Kim ◽  
H. Frederik Nijhout ◽  
Michael C. Reed

Many enzymes in one-carbon metabolism (OCM) are up- or down-regulated by the sex hormones which vary diurnally and throughout the menstrual cycle. During pregnancy, estradiol and progesterone levels increase tremendously to modulate physiological changes in the reproductive system. In this work, we extend and improve an existing mathematical model of hepatic OCM to understand the dynamic metabolic changes that happen during the menstrual cycle and pregnancy due to estradiol variation. In particular, we add the polyamine drain on S-adenosyl methionine and the direct effects of estradiol on the enzymes cystathionine β-synthase (CBS), thymidylate synthase (TS), and dihydrofolate reductase (DHFR). We show that the homocysteine concentration varies inversely with estradiol concentration, discuss the fluctuations in 14 other one-carbon metabolites and velocities throughout the menstrual cycle, and draw comparisons with the literature. We then use the model to study the effects of vitamin B12, vitamin B6, and folate deficiencies and explain why homocysteine is not a good biomarker for vitamin deficiencies. Additionally, we compute homocysteine throughout pregnancy, and compare the results with experimental data. Our mathematical model explains how numerous homeostatic mechanisms in OCM function and provides new insights into how homocysteine and its deleterious effects are influenced by estradiol. The mathematical model can be used by others for further in silico experiments on changes in one-carbon metabolism during the menstrual cycle and pregnancy.


2021 ◽  
Vol 177 ◽  
pp. S128
Author(s):  
Sergio Rius-Pérez ◽  
Isabel Torres-Cuevas ◽  
Salvador Pérez ◽  
Pablo Martí-Andrés ◽  
Raquel Taléns ◽  
...  

2021 ◽  
Vol 22 (22) ◽  
pp. 12201
Author(s):  
Hyoung-Yun Han ◽  
Mi-Sun Choi ◽  
Seokjoo Yoon ◽  
Je-Won Ko ◽  
Sang-Kyum Kim ◽  
...  

Ifosfamide is an alkylating agent, a synthetic analogue of cyclophosphamide, used to treat various solid cancers. In this study, the toxicity of ifosfamide was evaluated using single-and multiple-dose intraperitoneal administration in rats under Good Laboratory Practice guidelines, and an additional microarray experiment was followed to support toxicological findings. A single dose of ifosfamide (50 mg/kg) did not induce any pathological changes. Meanwhile, severe renal toxicity was observed in the 7 and 28 days consecutively administered groups, with significant increases in blood urea nitrogen and creatinine levels. In the tox-list analysis, cholesterol synthesis-related genes were mostly affected in the liver and renal failure-related genes were affected in the kidney after ifosfamide administration. Moreover, interferon regulatory factor 7 was selected as the main upstream regulator that changed in both the liver and kidney, and was found to interact with other target genes, such as ubiquitin specific peptidase 18, radical S-adenosyl methionine domain containing 2, and interferon-stimulated gene 15, which was further confirmed by real-time RT-PCR analysis. In conclusion, we confirmed kidney-biased ifosfamide organ toxicity and identified identically altered genes in both the liver and kidney. Further comprehensive toxicogenomic studies are required to reveal the exact relationship between ifosfamide-induced genes and organ toxicity.


Author(s):  
K. Lakshmi ◽  
K. Padmaja

Background: Treatment of canine liver diseases is often supportive and enables combinations of drug therapy and dietary support. Many nutraceutical compounds that have anti-oxidant properties have been suggested as supplements in animals suffering with hepatic diseases especially silymarin and S-adenosyl methionine The current study was aimed to evaluate therapeutic efficacy of certain nutraceuticals in the management of hepatic disorders in dogs. Methods: Dogs presented to Veterinary Hospital, Bhoiguda, Hyderabad with the clinical signs suggestive of hepatobiliary disorders were selected. Detailed history of the affected dogs was collected. Later, these cases were subjected for detailed clinical examination. While, apparently healthy dogs presented for general health checkup and vaccination with no clinical condition in the age group of 2-5 years were selected randomly as healthy control group for this study. Result: The present investigation was under taken to study the therapeutic efficacy of certain nutraceuticals in the management of hepatic disorders in dogs. Based on history, clinical signs, haemato biochemistry and ultrasonography, 32 dogs were histologically confirmed as hepatic disorders which formed the largest group. These dogs were selected for therapeutic trial. Apart from the specific drugs, addition of nutraceuticals like Silymarin and S-adenosyl methionine therapy was effective in the treatment of hepatic disorders.


Molecules ◽  
2021 ◽  
Vol 26 (20) ◽  
pp. 6151
Author(s):  
Ibrahim H. Eissa ◽  
Mohamed M. Khalifa ◽  
Eslam B. Elkaeed ◽  
Elsayed E. Hafez ◽  
Aisha A. Alsfouk ◽  
...  

In continuation of our previous effort, different in silico selection methods were applied to 310 naturally isolated metabolites that exhibited antiviral potentialities before. The applied selection methods aimed to pick the most relevant inhibitor of SARS-CoV-2 nsp10. At first, a structural similarity study against the co-crystallized ligand, S-Adenosyl Methionine (SAM), of SARS-CoV-2 nonstructural protein (nsp10) (PDB ID: 6W4H) was carried out. The similarity analysis culled 30 candidates. Secondly, a fingerprint study against SAM preferred compounds 44, 48, 85, 102, 105, 182, 220, 221, 282, 284, 285, 301, and 302. The docking studies picked 48, 182, 220, 221, and 284. While the ADMET analysis expected the likeness of the five candidates to be drugs, the toxicity study preferred compounds 48 and 182. Finally, a density-functional theory (DFT) study suggested vidarabine (182) to be the most relevant SARS-Cov-2 nsp10 inhibitor.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Song Meng ◽  
Andrew D. Steele ◽  
Wei Yan ◽  
Guohui Pan ◽  
Edward Kalkreuter ◽  
...  

AbstractNature forms S-S bonds by oxidizing two sulfhydryl groups, and no enzyme installing an intact hydropersulfide (-SSH) group into a natural product has been identified to date. The leinamycin (LNM) family of natural products features intact S-S bonds, and previously we reported an SH domain (LnmJ-SH) within the LNM hybrid nonribosomal peptide synthetase (NRPS)-polyketide synthase (PKS) assembly line as a cysteine lyase that plays a role in sulfur incorporation. Here we report the characterization of an S-adenosyl methionine (SAM)-dependent hydropersulfide methyltransferase (GnmP) for guangnanmycin (GNM) biosynthesis, discovery of hydropersulfides as the nascent products of the GNM and LNM hybrid NRPS-PKS assembly lines, and revelation of three SH domains (GnmT-SH, LnmJ-SH, and WsmR-SH) within the GNM, LNM, and weishanmycin (WSM) hybrid NRPS-PKS assembly lines as thiocysteine lyases. Based on these findings, we propose a biosynthetic model for the LNM family of natural products, featuring thiocysteine lyases as PKS domains that directly install a -SSH group into the GNM, LNM, or WSM polyketide scaffold. Genome mining reveals that SH domains are widespread in Nature, extending beyond the LNM family of natural products. The SH domains could also be leveraged as biocatalysts to install an -SSH group into other biologically relevant scaffolds.


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