scholarly journals Impacts of Embryonic Thermal Programming on the Expression of Genes Involved in Foie gras Production in Mule Ducks

2021 ◽  
Vol 12 ◽  
Author(s):  
William Massimino ◽  
Charlotte Andrieux ◽  
Sandra Biasutti ◽  
Stéphane Davail ◽  
Marie-Dominique Bernadet ◽  
...  

Embryonic thermal programming has been shown to improve foie gras production in overfed mule ducks. However, the mechanisms at the origin of this programming have not yet been characterized. In this study, we investigated the effect of embryonic thermal manipulation (+1°C, 16 h/24 h from embryonic (E) day 13 to E27) on the hepatic expression of genes involved in lipid and carbohydrate metabolisms, stress, cell proliferation and thyroid hormone pathways at the end of thermal manipulation and before and after overfeeding (OF) in mule ducks. Gene expression analyses were performed by classic or high throughput real-time qPCR. First, we confirmed well-known results with strong impact of OF on the expression of genes involved in lipid and carbohydrates metabolisms. Then we observed an impact of OF on the hepatic expression of genes involved in the thyroid pathway, stress and cell proliferation. Only a small number of genes showed modulation of expression related to thermal programming at the time of OF, and only one was also impacted at the end of the thermal manipulation. For the first time, we explored the molecular mechanisms of embryonic thermal programming from the end of heat treatment to the programmed adult phenotype with optimized liver metabolism.

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Jing Li ◽  
Srikant Viswanadha ◽  
Juan J. Loor

Dietarytrans-10,cis-12-conjugated linoleic acid (trans-10,cis-12-CLA) fed to obese and nonobese rodents reduces body fat but leads to greater liver mass due to steatosis. The molecular mechanisms accompanying such responses remain largely unknown. Our study investigated the effects of chronic lowtrans-10,cis-12-CLA supplementation on hepatic expression of 39 genes related to metabolism, inflammation, and stress in growing mice. Feeding a diet supplemented with 0.3%trans-10,cis-12-CLA (wt/wt basis) for 6 weeks increased liver mass and concentration of long-chain fatty acids (LCFAs) in liver, while adipose tissue mass decreased markedly. These changes were accompanied by greater expression of genes involved in LCFA uptake (Cd36), lipogenesis, and triacylglycerol synthesis (Acaca,Gpam,Scd,Pck1,Plin2). Expression of these genes was in line with upregulation of the lipogenic transcription factorSrebf1. Unlike previous studies where higher >0.50% of the diet) doses oftrans-10,cis-12-CLA were fed, we found greater expression of genes associated with VLDL assembly/secretion (Mttp,Cideb), ketogenesis (Hmgcs2,Bdh1), and LCFA oxidation (Acox1,Pdk4) in response totrans-10,cis-12-CLA. Dietary CLA, however, did not affect inflammation- and stress-related genes. Results suggested that a chronic low dose of dietary CLA increases liver mass and lipid accumulation due to activation of lipogenesis and insufficient induction of LCFA oxidation and VLDL assembly/secretion.


Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2771-2771
Author(s):  
Silvia Gutiérrez Cosío ◽  
Esteban Ballestar ◽  
Carlos Santamaría ◽  
Belén Blanco ◽  
Luis Ignacio Sánchez Abarca ◽  
...  

Abstract Abstract 2771 Introduction: We have previously shown that 5-azaC inhibits T-cells proliferation and favours the development of Tregs which decreases the risk of GVHD after allogeneic transplantation. This is at least in part due to the effect of the drug on the expression of genes such as FOXP3. Nevertheless, considering the unspecific effect of 5-azaC, it could also favour the overexpression of other genes related to the regulation of the immune response such as TBET, GATA3, IFNg or IL-2, which in turn would favour the development of a Th1, Th2 or Th17 polarization instead of a Treg expansion. In the current study we have evaluated the effect of 5-azaC on these genes in order to know the mechanisms involved in the effect of the drug on the immune response. Methods: We analyzed TBET, GATA3, FOXP3, IFNg and IL-2 mRNA expression of T lymphocytes by RT-PCR after exposure to 1mM 5-azaC during eleven days of culture. These T cells were cultured in medium alone or stimulated with plate-bound anti-CD3 (5 mg/ml) plus soluble anti-CD28 (2.5 mg/ml). Furthermore, we analyzed the methylation status of the promoters of these genes before and after 5-azaC treatment. Results: The expression of TBET, GATA3 and RORγ is not significantly affected by the exposure to the drug whereas the expression of FOXP3 significantly increases along the culture. Regarding IFNg and IL-2 expression no increased expression was observed after exposure to the drug at different time-points along the 11 days of culture. Upon analyzing the mathylation status of the promoter of these genes, we observed that in steady state the promoter of TBET and GATA is demethylated, which is in contrast to FOXP3 promoter. For this reason, the exposure to the drug decreases the methylation status of the promoter of FOXP3 while there is no effect on the promoters of TBET or RORg, thus justifying the absence of effect on the expression of these genes. By contrat, the promoter of both IFNg and IL-2 is methylated prior to the exposure to 5-azaC and it is demethylated after exposure to the drug, which is in contrast to the absence of increased expression of these genes. Accordingly, other mechanisms in addition to the epigenetic regulation of the promoter of IFNg and IL-2 are responsible for their expression in this model. Conclusions: In the current study we show by the first time the effect of 5-azaC on the promoters of genes which regulate the immune response. While no effect was observed for TBET, and GATA3 5-azaC induces a strong demethylation in the promoter of IFN or IL-2. In spite of this effect there is no increase in their expression which could be due to the overexpression of FOXP3 or to additional mechanisms involved in their regulation which are currently being evaluated. Disclosures: Cañizo: Celgene: Membership on an entity's Board of Directors or advisory committees. San Miguel:Celgene: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Jangssen-cilag: Membership on an entity's Board of Directors or advisory committees; millennium: Membership on an entity's Board of Directors or advisory committees. Off Label Use: The drug used in this study is the demethylating agent 5-azacytidine (5-azaC) and the purpose is the inhibition of graft versus host disease.


Cartilage ◽  
2020 ◽  
pp. 194760352097325
Author(s):  
Yang Yang ◽  
Yawei Wang ◽  
Haobo Jia ◽  
Bing Li ◽  
Dan Xing ◽  
...  

Objective Osteoarthritis (OA) is an incurable joint disease characterized by pronounced pain. MicroRNAs constitute epigenetic mechanisms that may affect OA progression by contributing to changes in chondrocyte phenotype. This study investigates for the first time whether there is a link between miRNA-1 (miR-1) and OA pathogenesis, and the molecular mechanisms involved. Design OA-associated gene expression, including MMP-13, ADAMTS5, and COL2A1 was compared in chondrocytes from non-OA and OA cartilage, and in SW1353 cells over- and underexpressing miR-1. Bioinformatics and luciferase reporter assay were conducted to confirm whether FZD7 was a target of miR-1. The effects of miR-1 on FZD7 expression and downstream Wnt/β-catenin signalling were investigated. Results Non-OA and OA chondrocytes differed significantly in the expression of miR-1 and OA-associated genes. MiR-1 over- and underexpression in SW1353 cells, respectively, reduced and enhanced gene expression associated with cartilage catabolism. FZD7, which has an important role in the Wnt/β-catenin signaling pathway, was shown to be a potential target of miR-1. MiR-1 binding to FZD7 increased the levels of phosphorylated (inactivated) β-catenin, thereby preventing downstream β-catenin signaling. Conclusions Inhibition of Wnt/β-catenin signaling by miR-1 in chondrocytes may attenuate the expression of genes that regulate the activity of catabolic enzymes. This finding may be useful for future investigations of molecular targets for OA treatment.


2020 ◽  
Author(s):  
Changshui Zhuang ◽  
Ying Liu ◽  
Chaobo Yuan ◽  
Shengqiang Fu ◽  
Weifeng Yang ◽  
...  

Abstract Objectives A subclass of long non-coding RNAs (lncRNAs), categorized as miRNA-host gene lncRNAs (lnc-miRHGs), is processed to produce miRNAs and involve in cancer progression. This work aimed to investigate the influence and the molecular mechanisms of lnc-miRHGs MIR497HG in bladder cancer (BCa). Materials and methods The miR-497 and miR-195 were derived from MIR497HG. Cell proliferation, migration and invasion assays were used to measure the function of MIR497HG, miR-497 and miR-195 in BCa. Bioinformatics, RT-qPCR, western blot, luciferase reporter assay, ChIP, and so on, were used to reveal the upstream and downstream mechanisms of MIR497HG in BCa. Results We identified that lnc-miRHG MIR497HG and two harbored miRNAs, miR-497 and miR-195, were downregulated in BCa by analyzing TCGA and our dataset. MIR497HG overexpression inhibited BCa cell proliferation, migration and invasion in vitro. MiR-497/miR-195 inhibitor rescued significantly the inhibiton effects of overexpression of MIR497HG in BCa. Mechanistically, miR-497 and miR-195 coordinately suppressed multiple key components in Hippo/Yap and TGF-β signaling, and particularly attenuated the interaction between Yap and Smad3. In addition, E2F4 was proved to be critical for silencing MIR497HG transcription in BCa cells. Conclusions We propose for the first time that MIR497HG suppressed BCa progression and its upstream and downstream mechanisms. Blocking the pathological process may be a potential strategy for the treatment of BCa.


PeerJ ◽  
2017 ◽  
Vol 5 ◽  
pp. e3726 ◽  
Author(s):  
Jun Xiao ◽  
Xiaowei Li ◽  
Juan Liu ◽  
Xiu Fan ◽  
Huifen Lei ◽  
...  

Background Tibetans have lived at high altitudes for thousands of years, and they have unique physiological traits that enable them to tolerate this hypoxic environment. However, the genetic basis of these traits is still unknown. As a sensitive and highly efficient technique, RT-qPCR is widely used in gene expression analyses to provide insight into the molecular mechanisms underlying environmental changes. However, the quantitative analysis of gene expression in blood is limited by a shortage of stable reference genes for the normalization of mRNA levels. Thus, systematic approaches were used to identify potential reference genes. Results The expression levels of eight candidate human reference genes (GAPDH, ACTB, 18S RNA, β2-MG, PPIA, RPL13A, TBP and SDHA) were assessed in blood from hypoxic environments. The expression stability of these selected reference genes was evaluated using the geNorm, NormFinder and BestKeeper programs. Interestingly, RPL13A was identified as the ideal reference gene for normalizing target gene expression in human blood before and after exposure to high-altitude conditions. Conclusion These results indicate that different reference genes should be selected for the normalization of gene expression in blood from different environmental settings.


1990 ◽  
Vol 29 (05) ◽  
pp. 215-220 ◽  
Author(s):  
R. Benning ◽  
K. Nagel ◽  
M. Jugenheimer ◽  
S. Fischer ◽  
S. Worthmann ◽  
...  

A new 99mTc-labelled tracer (99mTc-Sestanriibi) was used for the first time to demonstrate the perfusion of the skeletal muscle. In 16 patients with obstructive atherosclerosis of the lower limbs the change of perfusion of thigh and lower leg was studied with SPECT before and after vascular surgery (n = 11) or percutaneous transluminal angioplasty (n = 5). Comparative results of scintigraphic measurements and clinical observations (ancle-arm pressure, treadmill test) in 10 surgical patients (14 operated legs) showed correct positive or negative results in 86% (12/14).


2019 ◽  
Vol 23 (2) ◽  
pp. 117-119 ◽  
Author(s):  
D. N. Paskalev ◽  
B. T. Galunska ◽  
D. Petkova-Valkova

Tamm–Horsfall Protein (uromodulin) is named after Igor Tamm and Franc Horsfall Jr who described it for the first time in 1952. It is a glycoprotein, secreted by the cells in the thick ascending limb of the loop of Henle. This protein will perform a number of important pathophysiological functions, including protection against uroinfections, especially caused by E. Сoli, and protection against formation of calcium concernments in the kidney. Igor Tamm (1922-1995) is an outstanding cytologist, virologist and biochemist. He is one of the pioneers in the study of viral replication. He was born in Estonia and died in the USA. In 1964 he was elected for a professorship in Rockefeller Institute for Medical Research, where has been working continuously. Since 1959, he became a head of the virology lab established by his mentor and co-author Franc Horsfall. In the course of studies on the natural inhibitor of viral replication, Tamm and Horsfall isolated and characterized biochemically a new protein named after their names. Franc Lappin Horsfall Jr (1906-1971) was a well-known clinician and virologist with remarkable achievements in internal medicine. He was born and died in the USA. He worked in the Rockefeller Hospital from 1934 to 1960, then in the Center for Cancer Research at the Sloan-Kettering Institute. Here he was a leader of a research team studying the molecular mechanisms of immunity, the effects of chemotherapy with benzimidazole compounds (together with I. Tamm), coxsackie viruses, herpes simplex virus, etc. 


Psychiatry ◽  
2020 ◽  
Vol 18 (4) ◽  
pp. 16-25
Author(s):  
N. S. Karpova ◽  
O. S. Brusov ◽  
I. V. Oleichik ◽  
M. I. Faktor ◽  
N. S. Levchenko ◽  
...  

Background: currently, it has been proven that the pathogenesis of endogenous mental disorders is associated with the process of neuroinflammation in the brain of patients. It is also known that chronic neuroinflammation, accompanied by a violation the permeability of the blood-brain barrier. It is accompanied by the activation of platelets that generate procoagulant microparticles, which leads to a disturbance of the hemostasis system, causing an increase in blood clotting in patients. Objective: to investigate the dynamics of procoagulant activity of blood in patients with endogenous mental disorders before and after psychopharmacotherapy.Patients and methods: the study included 185 patients aged 16 to 64 years with the following mental disorders: schizophrenia with attack-like/attack-progressive/continuous type of course (F20.00–2), affective disease (F31.1–5; F32.0–3; F33.0–3), schizotypal disorder with affective fluctuations (F21.3–4). The thrombodynamic test (TD) was performed on T-2 Trombodynamis device according to the manufacturer’s instructions (Hemacore LLC, Moscow, Russia). All patients received standard pharmacotherapy according to their condition.Results: a significant decrease of procoagulant activity of spontaneous clots in the patients’ blood after psychopharmacological treatment is observed. Our data on the positive dynamics of changes in the values of TD test’s indicators in most of the examined patients suggest that a decrease in the coagulation activity of the patients’ blood as a result of treatment may be associated with the anti- inflammatory effect of antipsychotics and antidepressants.Conclusion: for the first time, it was shown that there is a positive dynamic in changing the values of the main parameters of the TD test in most patients with endogenous mental diseases. The results of TD tests can be the basis for monitoring the response to therapy.


2021 ◽  
Vol 20 ◽  
Author(s):  
Rabih Roufayel ◽  
Rabih Mezher ◽  
Kenneth B. Storey

: Selected transcription factors have critical roles to play in organism survival by regulating the expression of genes that control the adaptations needed to handle stress conditions. The retinoblastoma (Rb) protein coupled with the E2F transcription factor family was demonstrated to have roles in controlling the cell cycle during freezing and associated environmental stresses (anoxia, dehydration). Rb phosphorylation or acetylation at different sites provide a mechanism for repressing cell proliferation that is under the control of E2F transcription factors in animals facing stresses that disrupt cellular energetics or cell volume controls. Other central regulators of the cell cycle including Cyclins, Cyclin dependent kinases (Cdks), and checkpoint proteins detect DNA damage or any improper replication, blocking further progression of cell cycle and interrupting cell proliferation. This review provides an insight into the molecular regulatory mechanisms of cell cycle control, focusing on Rb-E2F along with Cyclin-Cdk complexes typically involved in development and differentiation that need to be regulated in order to survive extreme cellular stress.


2018 ◽  
Vol 18 (7) ◽  
pp. 1025-1031
Author(s):  
Cheng Luo ◽  
Di Wu ◽  
Meiling Chen ◽  
Wenhua Miao ◽  
Changfeng Xue ◽  
...  

Background: Different saponins from herbs have been used as tonic or functional foods, and for treatment of various diseases including cancers. Although clinical data has supported the function of these saponins, their underlying molecular mechanisms have not been well defined. Methods: With the simulated hypoxia created by 8 hours of Cu++ exposure and following 24 hour incubation with different concentration of saponins in HepG2 cells for MTT assay, migration and invasion assays, and for RT-PCR, and with each group of cells for immunofluorescence observation by confocal microscopy. Results: ZC-4 had the highest rate of inhibition of cell proliferation by MTT assay, and the highest inhibition of migration rate by in vitro scratch assay, while ZC-3 had the highest inhibition of invasion ratio by transwell assay. Under the same simulated hypoxia, the molecular mechanism of saponin function was conducted by measuring the gene expression of Hypoxia Inducible Factor (HIF)-1α through RT-PCR, in which ZC-3 showed a potent inhibition of gene HIF-1α. For the protein expression by immunofluorescence staining with confocal microscopy, HIF-1α was also inhibited by saponins, with the most potent one being ZC-4 after eight hours’ relatively hypoxia incubation. Conclusion: Saponins ZC-4 and ZC-3 have the potential to reduce HepG2 cell proliferation, migration and invasion caused by hypoxia through effectively inhibiting the gene and protein expression of HIF-1α directly and as antioxidant indirectly


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