scholarly journals Influence of Age and Immunostimulation on the Level of Toll-Like Receptor Gene (TLR3, 4, and 7) Expression in Foals

Animals ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 1966
Author(s):  
Anna Migdał ◽  
Łukasz Migdał ◽  
Maria Oczkowicz ◽  
Adam Okólski ◽  
Anna Chełmońska-Soyta

The aim of this study was to investigate the molecular mechanisms leading to the identification of pathogens by congenital immune receptors in foals up to 60 days of age. The study was conducted on 16 foal Polish Pony Horses (Polish Konik) divided into two study groups: control (n = 9) and experimental (n = 7). Foals from the experimental group received an intramuscular duplicate injection of 5 mL of Biotropina (Biowet) at 35 and 40 days of age. The RNA isolated from venous blood was used to evaluate the expression of theTLR3, TLR4, and TLR7 genes using RT-PCR. The results of the experiment demonstrated a statistically significant increase in the level of TLR3 gene expression and a decrease in the level ofTLR4 gene expression with foal aging. The level of TLR7 gene expression did not show age dependence. Immunostimulation with Biotropina had a significant impact on the level of the genes’ expression for Toll-like receptors. It increased the level of TLR4 expression and decreased TLR3 expression. Thus, it was concluded that the expression of theTLR3 and TLR4genes in peripheral blood cells is dependent on age. This experiment demonstrated a strong negative correlation between TLR3 and TLR4 gene expression.

1994 ◽  
Vol 344 (1309) ◽  
pp. 291-304 ◽  

The oxytocin receptor, a seven transmembrane domain, G protein-linked receptor molecule, plays a central role in determining the endocrine function of the ruminant uterine endometrium. During non- pregnant cycles the control of this molecule by circulating steroid hormones leads to regression of the corpora lutea. The kinetics of the mechanisms involved determine the time at which luteolysis occurs, and therefore the length of the oestrous cycle. In pregnancy, secretions of the trophoblast block endometrial oxytocin receptor gene expression and lead to luteal maintenance. An understanding of the molecular mechanisms involved in the steroidal control of oxytocin receptor gene expression will provide an explanation for the relative constancy of oestrous cycle lengths in non-pregnant animals. Unravelling the way in which trophoblast products block expression of the oxytocin receptor gene will lead to a better understanding of the reasons for the high rate of embryonic loss in domestic ruminants.


2013 ◽  
Vol 33 (9) ◽  
pp. 1711-1722 ◽  
Author(s):  
Sivapriya Ramamoorthy ◽  
John A. Cidlowski

Glucocorticoids are among the most potent and effective agents for treating inflammatory diseases and hematological cancers. However, subpopulations of patients are often resistant to steroid therapy, and determining the molecular mechanisms that contribute to glucocorticoid resistance is thus critical to addressing this clinical problem affecting patients with chronic inflammatory disorders. Since the cellular level of the glucocorticoid receptor (GR) is a critical determinant of glucocorticoid sensitivity and resistance, we investigated the molecular mechanisms mediating repression of glucocorticoid receptor gene expression. We show here that glucocorticoid-induced repression of GR gene expression is mediated by inhibition of transcription initiation. This process is orchestrated by the recruitment of agonist-bound GR to exon 6, followed by the assembly of a GR-NCoR1-histone deacetylase 3-containing repression complex at the transcriptional start site of the GR gene. A functional negative glucocorticoid response element (nGRE) in exon 6 of the GR gene and a long-range interaction occurring between this intragenic response element and the transcription start site appear to be instrumental in this repression. This autoregulatory mechanism of repression implies that the GR concentration can coordinate repression with excess ligand, regardless of the combinatorial associations of tissue-specific transcription factors. Consequently, the chronic nature of inflammatory conditions involving long-term glucocorticoid administration may lead to constitutive repression of GR gene transcription and thus to glucocorticoid resistance.


2021 ◽  
Author(s):  
Mohammad Javad Boozhmehrani ◽  
Gilda Eslami ◽  
Ali Khamesipour ◽  
Abbas Ali Jafari ◽  
Mahmood Vakili

Abstract Background: Leishmaniasis is one of the common diseases transmitted by sand flies in tropical and subtropical regions of the world. Currently, antimonal derivatives are the first line of treatment. Some of the members of the ATP-binding cassette (ABC) family of Leishmania are shown to be associated with resistance to antimonial. In this study, we evaluated ABCI4, ABCG2, ABCC7, and ABCC3 gene expression in Leishmania isolated from patients with non-healing cutaneous leishmaniasis. Results: Five cases were treatment failure that all of them were identified as L. major. All treatment failure clinical isolates were L. major. Gene expression analysis in treatment failure isolates showed that the ABC transported genes had a different pattern in each isolate. ABCC7 had overexpression in all isolates. Among the treatment failure isolates, only one sample had overexpression in all ABC transporter genes under study. Conclusions: Treatment failure has been reported for cutaneous leishmaniasis worldwide. Knowledge of the molecular mechanisms of treatment failure could solve this problem. ABC transporter genes are considered controversy over the mechanisms of treatment failure outcomes. In this study, we showed that ABC transporter genes could be considered one the important mechanisms.


Author(s):  
О.М. Плотникова ◽  
М.Ю. Скоблов

На сегодняшний день известно около 7000 наследственных заболеваний. Однако современные методы ДНК диагностики выявляют причину возникновения заболеваний примерно в 40% случаев. Отчасти это обусловлено сложностью и большим разнообразием молекулярных механизмов их патогенеза. МикроРНК являются одним из мощнейших регуляторов экспрессии генов. Однако участие их в патогенезе наследственных заболеваний пока недостаточно изучено из-за сложностей поиска таких нарушений. В данной работе проведён анализ описанных механизмов патогенеза наследственных заболеваний, опосредованных нарушениями регуляции экспрессии генов посредством микроРНК. Такие случаи были выявлены при таких наследственных заболеваниях как муковисцидоз, миодистрофия Дюшенна, бета-талассемия, глаукома, лице-лопаточно-плечевая миодистрофия Ландузи-Дежерина, болезнь Гиршпрунга, синдром Ретта, синдром Туретта, пемфигус (болезнь Хейли-Хейли). To date, about 7,000 hereditary diseases are known. However, modern diagnostic methods reveal the cause of the disease in about 40% of cases. This is partly due to the complexity and wide variety of molecular mechanisms of pathogenesis. MicroRNAs are one of the most powerful genes expression regulators. But their participation in the pathogenesis of hereditary diseases has not yet been studied enough because of the difficulties in finding such disorders. In this work, we collected and analyzed pathogenesis of hereditary diseases mediated by dysregulation of gene expression by microRNA. such cases have been identified for such hereditary diseases as cystic fibrosis, Duchenne muscular dystrophy, beta-thalassemia, glaucoma, facioscapulohumeral muscular dystrophy Landouzy-Dejerine, Hirschsprung disease, Rett syndrome, Tourette syndrome, pemphigus (Hailey-Hailey disease).


2021 ◽  
Vol 43 (2) ◽  
pp. 665-675
Author(s):  
Olga Kuten-Pella ◽  
Andrea De Luna ◽  
Karina Kramer ◽  
Markus Neubauer ◽  
Stefan Nehrer ◽  
...  

Intra-articular injection of different types of blood-derived products is gaining popularity and clinical importance in the treatment of degenerative cartilage disorders such as osteoarthritis. The regenerative potential of two types of platelet-rich plasma (PRP), prepared in the presence of EDTA (EPRP) and citrate (CPRP) and an alternative blood product-hyperacute serum (hypACT) was evaluated using a 3D osteoarthritic chondrocyte pellet model by assessing the metabolic cell activity, cartilage-related gene expression and extracellular matrix deposition within the pellets. Chondrocyte viability was determined by XTT assay and it revealed no significant difference in metabolic activity of OA chondrocyte pellets after supplementation with different blood products. Nevertheless, the selection of blood products influenced the cartilage-related genes expression, ECM morphology and the tissue quality of pellets. Both PRP types had a different biological effect depending upon concentration and even though CPRP is widely used in clinics our assessment did not reveal good results in gene expression either tissue quality. HypACT supplementation resulted in superior cartilage-related genes expression together with tissue quality and seemed to be the most stable product since no remarkable changes were observed between the two different concentrations. All in all, for successful regenerative therapy, possible molecular mechanisms induced by blood-derived products should be always carefully investigated and adapted to the specific medical indications.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Laura Ramo-Fernández ◽  
Anja M. Gumpp ◽  
Christina Boeck ◽  
Sabrina Krause ◽  
Alexandra M. Bach ◽  
...  

AbstractThe neuropeptide oxytocin (OXT) and its receptor (OXTR) modulate interpersonal relationships, particularly mother–child interactions. DNA methylation (DNAm) changes of the OXTR gene were observed in individuals who experienced Childhood Maltreatment (CM). A modulatory role of single nucleotide polymorphisms (SNP) within OXTR in association with CM on the regulation of OXTR was also postulated. Whether these CM-induced epigenetic alterations are biologically inherited by the offspring remains unknown. We thus investigated possible intergenerational effects of maternal CM exposure on DNAm and OXTR gene expression, additionally accounting for the possible influence of three SNP: rs53576 and rs2254298 (OXTR gene), and rs2740210 (OXT gene). We used the Childhood Trauma Questionnaire to classify mothers into individuals with (CM+) or without CM (CM−). Maternal peripheral immune cells were isolated from venous blood (N = 117) and fetal immune cells from the umbilical cord (N = 113) after parturition. DNA methylation was assessed using MassARRAY. Taqman assays were performed for genotyping and gene expression analyses. Among mothers, CM was not associated with OXTR mean methylation or gene expression. However, four CpG sites showed different methylation levels in CM− compared to CM+. In mothers, the OXTR rs53576 and OXT rs2740210 allelic variations interacted with CM load on the OXTR mean methylation. Maternal and newborns’ mean methylation of OXTR were positively associated within CM− dyads, but not in CM+ dyads. We show gene×environment interactions on the epigenetic regulation of the oxytocinergic signaling and show the intergenerational comparability of the OXTR DNAm might be altered in infants of CM+ mothers.


2021 ◽  
Author(s):  
Nasrin Heidarieh ◽  
Maryam Najafifard ◽  
Ali Haeri Rohani ◽  
Akram Eidi

Abstract Background and objective: Learning and memory are necessary for survival. The hippocampus plays a significant role in learning process. GABAA receptors in the hippocampus are effective in learning and memory mechanism. The present study effect of tarragon hydroalcoholic extract and coumarin on memory, tissue index and GABAA receptor gene expression in the hippocampus of male rats. Methodology: 56 Wistar rats were used and randomized in 7 groups (N = 8). These groups included the intact, receiving DMSO, receiving tarragon hydroalcoholic extract doses of 25, 50 and 100 mg/kg and receiving coumarin dose of 3, 5 mg/kg. They have undergone treatment intraperitoneally once a day for two weeks. The shuttle box was used for the memory retention test. The rats were killed according to the research ethical codes after the tests were done. When the brains of rats were removed, 4 brains in each group were chosen for the histological test using Nissl staining. In the other four brains, the hippocampus was removed immediately. The hippocampus was located in a microtube and was frozen by liquid nitrogen. Finally, a gene expression test was performed using real-time PCR. Results the findings of the present study reveal that there was no significant difference between of solvent recipients and the intact group in the memory retention test, the number of healthy hippocampal pyramidal neurons, and the expression of the GABAA gene. The treated groups with various doses of hydroalcoholic extract of tarragon and coumarin showed decreased in the memory retention test and the number of healthy pyramidals neurons as well as a significant increase in GABAA- α5 and GABAA- α2 genes expression compared to the group receiving solvent. Conclusion Tarragon hydroalcoholic extract and coumarin affects memory impairment through increasing the GABAA-α5 and GABAA-α2 genes expression and decreasing the number of healthy hippocampal neurons.


2016 ◽  
Vol 30 (1) ◽  
Author(s):  
A. Runov ◽  
◽  
E Kurchakova ◽  
D Khaschevskaya ◽  
O Moiseeva ◽  
...  

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