scholarly journals Transcriptome Analysis of Testes and Uterus: Reproductive Dysfunction Induced by Toxoplasma gondii in Mice

2020 ◽  
Vol 8 (8) ◽  
pp. 1136
Author(s):  
Junjie Wang ◽  
Tanghui Liu ◽  
Yasser S. Mahmmod ◽  
Zipeng Yang ◽  
Jiexing Tan ◽  
...  

Toxoplasma gondii (T. gondii) infection in female mammals during pregnancy can result in poor pregnancy. Similarly, it can result in male reproductive disorders in male mammals. Although the testes and uterus have very different biological makeup, they are still both attacked by T. gondii resulting in reproductive dysfunctions. We hypothesized that there are significant common genes in the testes and uterus that interact with T. gondii. Finding out and studying these genes is vital to understand the infection mechanism of T. gondii and the induced disease pathogenesis. To achieve this goal, we built a mice model of acute infection with T. gondii and the testes and uterus of the mice were sequenced by RNA-Seq. A total of 291 and 679 significantly differently expressed genes (DEGs) were obtained from the testes and the uterus, respectively. In the Gene Ontology (GO) analysis, part of the DEGs in the testes and uterus were related to 35 GO functions. When compared with the KEGG database, seven pathways affecting both the testes and uterus during the course of T. gondii infection were identified. In addition, Toxoplasmosis can significantly affect the expression of Nlrp5 and Insc leading to negative outcomes in the host. On the other hand, the host regulates Gbp7, Gbp2b, and Ifit3 to defend against T. gondii infection.

2020 ◽  
Author(s):  
Hiroto Yamamoto ◽  
Yutaro Uchida ◽  
Tomoki Chiba ◽  
Ryota Kurimoto ◽  
Takahide Matsushima ◽  
...  

AbstractBackgroundsSevoflurane is a most frequently used volatile anaesthetics, but its molecular mechanisms of action remain unclear. We hypothesized that specific genes play regulatory roles in whole brain exposed to sevoflurane. Thus, we aimed to evaluate the effects of sevoflurane inhalation and identify potential regulatory genes by RNA-seq analysis.MethodsEight-week old mice were exposed to sevoflurane. RNA from four medial prefrontal cortex, striatum, hypothalamus, and hippocampus were analysed using RNA-seq. Differently expressed genes were extracted. Their gene ontology terms and the transcriptome array data of the cerebral cortex of sleeping mice were analysed using Metascape, and the gene expression patterns were compared. Finally, the activities of transcription factors were evaluated using a weighted parametric gene set analysis (wPGSA). JASPAR was used to confirm the existence of binding motifs in the upstream sequences of the differently expressed genes.ResultsThe gene ontology term enrichment analysis result suggests that sevoflurane inhalation upregulated angiogenesis and downregulated neural differentiation in the whole brain. The comparison with the brains of sleeping mice showed that the gene expression changes were specific to anaesthetized mice. Sevoflurane induced Klf4 upregulation in the whole brain. The transcriptional analysis result suggests that KLF4 is a potential transcriptional regulator of angiogenesis and neural development.ConclusionsKlf4 was upregulated by sevoflurane inhalation in whole brain. KLF4 might promote angiogenesis and cause the appearance of undifferentiated neural cells by transcriptional regulation. The roles of KLF4 might be key to elucidating the mechanisms of sevoflurane induced functional modification in the brain.


PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0236771
Author(s):  
Hiroto Yamamoto ◽  
Yutaro Uchida ◽  
Tomoki Chiba ◽  
Ryota Kurimoto ◽  
Takahide Matsushima ◽  
...  

Backgrounds Sevoflurane is a most frequently used volatile anesthetics, but its molecular mechanisms of action remain unclear. We hypothesized that specific genes play regulatory roles in brain exposed to sevoflurane. Thus, we aimed to evaluate the effects of sevoflurane inhalation and identify potential regulatory genes by RNA-seq analysis. Methods Eight-week old mice were exposed to sevoflurane. RNA from medial prefrontal cortex, striatum, hypothalamus, and hippocampus were analysed using RNA-seq. Differently expressed genes were extracted and their gene ontology terms were analysed using Metascape. These our anesthetized mouse data and the transcriptome array data of the cerebral cortex of sleeping mice were compared. Finally, the activities of transcription factors were evaluated using a weighted parametric gene set analysis (wPGSA). JASPAR was used to confirm the existence of binding motifs in the upstream sequences of the differently expressed genes. Results The gene ontology term enrichment analysis result suggests that sevoflurane inhalation upregulated angiogenesis and downregulated neural differentiation in each region of brain. The comparison with the brains of sleeping mice showed that the gene expression changes were specific to anesthetized mice. Focusing on individual genes, sevoflurane induced Klf4 upregulation in all sampled parts of brain. wPGSA supported the function of KLF4 as a transcription factor, and KLF4-binding motifs were present in many regulatory regions of the differentially expressed genes. Conclusions Klf4 was upregulated by sevoflurane inhalation in the mouse brain. The roles of KLF4 might be key to elucidating the mechanisms of sevoflurane induced functional modification in the brain.


Author(s):  
Julio Toporovski ◽  
Simone Romano ◽  
Suzana Hartmann ◽  
Wanda Benini ◽  
Pedro Paulo Chieffi

The concomitance of nephrotic syndrome and acute infection by Toxoplasma gondii is a rare occurrence in humans. In this paper seven cases of children, ranging from 11 months to 7 year-old, with concomitant nephrotic syndrome and asymptomatic acute T. gondii infection are reported. In one of those patients only the administration of anti-Toxoplasma therapy was enough to control the clinical and laboratory manifestations of the disease. In the other patients it was necessary to introduce corticosteroids or other immunosuppressant drugs. Three patients had complete clinical and laboratory improvement and the remaining showed only a partial response.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 12.2-12
Author(s):  
I. Muller ◽  
M. Verhoeven ◽  
H. Gosselt ◽  
M. Lin ◽  
T. De Jong ◽  
...  

Background:Tocilizumab (TCZ) is a monoclonal antibody that binds to the interleukin 6 receptor (IL-6R), inhibiting IL-6R signal transduction to downstream inflammatory mediators. TCZ has shown to be effective as monotherapy in early rheumatoid arthritis (RA) patients (1). However, approximately one third of patients inadequately respond to therapy and the biological mechanisms underlying lack of efficacy for TCZ remain elusive (1). Here we report gene expression differences, in both whole blood and peripheral blood mononuclear cells (PBMC) RNA samples between early RA patients, categorized by clinical TCZ response (reaching DAS28 < 3.2 at 6 months). These findings could lead to identification of predictive biomarkers for TCZ response and improve RA treatment strategies.Objectives:To identify potential baseline gene expression markers for TCZ response in early RA patients using an RNA-sequencing approach.Methods:Two cohorts of RA patients were included and blood was collected at baseline, before initiating TCZ treatment (8 mg/kg every 4 weeks, intravenously). DAS28-ESR scores were calculated at baseline and clinical response to TCZ was defined as DAS28 < 3.2 at 6 months of treatment. In the first cohort (n=21 patients, previously treated with DMARDs), RNA-sequencing (RNA-seq) was performed on baseline whole blood PAXgene RNA (Illumina TruSeq mRNA Stranded) and differential gene expression (DGE) profiles were measured between responders (n=14) and non-responders (n=7). For external replication, in a second cohort (n=95 therapy-naïve patients receiving TCZ monotherapy), RNA-seq was conducted on baseline PBMC RNA (SMARTer Stranded Total RNA-Seq Kit, Takara Bio) from the 2-year, multicenter, double-blind, placebo-controlled, randomized U-Act-Early trial (ClinicalTrials.gov identifier: NCT01034137) and DGE was analyzed between 84 responders and 11 non-responders.Results:Whole blood DGE analysis showed two significantly higher expressed genes in TCZ non-responders (False Discovery Rate, FDR < 0.05): urotensin 2 (UTS2) and caveolin-1 (CAV1). Subsequent analysis of U-Act-Early PBMC DGE showed nine differentially expressed genes (FDR < 0.05) of which expression in clinical TCZ non-responders was significantly higher for eight genes (MTCOP12, ZNF774, UTS2, SLC4A1, FECH, IFIT1B, AHSP, and SPTB) and significantly lower for one gene (TND2P28M). Both analyses were corrected for baseline DAS28-ESR, age and gender. Expression of UTS2, with a proposed function in regulatory T-cells (2), was significantly higher in TCZ non-responders in both cohorts. Furthermore, gene ontology enrichment analysis revealed no distinct gene ontology or IL-6 related pathway(s) that were significantly different between TCZ-responders and non-responders.Conclusion:Several genes are differentially expressed at baseline between responders and non-responders to TCZ therapy at 6 months. Most notably, UTS2 expression is significantly higher in TCZ non-responders in both whole blood as well as PBMC cohorts. UTS2 could be a promising target for further analyses as a potential predictive biomarker for TCZ response in RA patients in combination with clinical parameters (3).References:[1]Bijlsma JWJ, Welsing PMJ, Woodworth TG, et al. Early rheumatoid arthritis treated with tocilizumab, methotrexate, or their combination (U-Act-Early): a multicentre, randomised, double-blind, double-dummy, strategy trial. Lancet. 2016;388(10042):343-55.[2]Bhairavabhotla R, Kim YC, Glass DD, et al. Transcriptome profiling of human FoxP3+ regulatory T cells. Human Immunology. 2016;77(2):201-13.[3]Gosselt HR, Verhoeven MMA, Bulatovic-Calasan M, et al. Complex machine-learning algorithms and multivariable logistic regression on par in the prediction of insufficient clinical response to methotrexate in rheumatoid arthritis. Journal of Personalized Medicine. 2021;11(1).Disclosure of Interests:None declared


2016 ◽  
Vol 2016 ◽  
pp. 1-4 ◽  
Author(s):  
Sakina Rashid ◽  
Grace Kinabo ◽  
Marissa Kellogg ◽  
William P. Howlett ◽  
Marieke C. J. Dekker

Neural tube defects result from failure of neural tube fusion during early embryogenesis, the fourth week after conception. The spectrum of severity is not uniform across the various forms of this congenital anomaly as certain presentations are not compatible with extrauterine life (anencephaly) while, on the other hand, other defects may remain undiagnosed as they are entirely asymptomatic (occult spina bifida). We report a child with previously normal neurological development, a devastating clinical course following superinfection of a subtle spina bifida defect which resulted in a flaccid paralysis below the level of the lesion and permanent neurological deficits following resolution of the acute infection and a back closure surgery.


2010 ◽  
Vol 19 (3) ◽  
pp. 152-156 ◽  
Author(s):  
Piassa Franciele Rossandra ◽  
Jacqueline Baptista de Araújo ◽  
Ronaldo César da Rosa ◽  
Rodrigo José Mattei ◽  
Rodrigo Costa da Silva ◽  
...  

Toxoplasma gondii infection has been diagnosed in pigs all over the world. Economical losses are generally related to reproductive disorders. Toxoplasma infection is also a matter of public health because tissue cysts of the parasite may remain in pork and pork products, and become sources of human infection. The objective of this study was to evaluate the frequency and risk factors associated with Toxoplasma infection in certified and non-certified pig breeding farms in the Toledo microregion, in the State of Paraná, Brazil which includes the cities of Toledo, Nova Santa Rosa, Sao José das Palmeiras and Sao Pedro do Iguaçu. Relative frequency of infection was 13.4%, independently of the type of farm. Logistic regression analysis showed that the following factors were associated with infection: absence of workers exclusive for each area of the farm, access of other animals to feeders and drinkers, lack of lids in drinkers, lack of rodent control measures, mean piglet number and weight at weaning per female.


2010 ◽  
Vol 138 (5-6) ◽  
pp. 333-336 ◽  
Author(s):  
Snezana Brkic ◽  
Gorana Gajski ◽  
Mirjana Bogavac ◽  
Daniela Maric ◽  
Vesna Turkulov ◽  
...  

Introduction Toxoplasmosis is an acute infectious anthropozoonotic disease with mild asymptomatic clinical manifestations in immunocompetent persons and more severe in immunocompromised patients. Acute infection in pregnancy can result in severe congenital toxoplasmosis with severe sequels. Objective Aims of study were to detect Toxoplasma gondii seroprevalence in general population of Vojvodina, Serbia, differences between genders and determination of seroprevalence in women of reproductive age and pregnant women. Methods Our retrospective study was conducted from 2006 to 2008 including 625 immunocompetent patients, hospitalized or observed as outpatients at the Clinical Centre of Vojvodina, Novi Sad. We performed commercial ELISA kits SERION - ELISA classic test by VIRION for the presence of specific IgG and IgM antibodies. According to seroepidemiological aim of the study, our results were presented only in qualitative values. Results We observed 173 male and 452 female patients. Seroprevalence in general population of Vojvodina was 38.1%. In male population seroprevalence was 45.7%, and in female population it was 35.2%, the difference which was statistically significant (p<0.05). Seroprevalence increased with age and seroconversion was detected to occur in persons aged about 20 years. In all female patients, 353 (78.1%) were in reproductive age with seroprevalence of 30%. In 161 pregnant women seroprevalence was 31.7%. Conclusion In this study we screened actual seroepidemiological situation to Toxoplasma gondii in Vojvodina, thus giving a contribution to the continuous epidemiological screening done in this region and in the country. According to our results, almost 70% of women in reproductive age were sensitive to primary acute infection during further pregnancies, which is highly important for the prevention of congenital toxoplasmosis. Although not routinely conducted in many countries, routine serological testing to Toxoplasma gondii in pregnant women and their education about preventive measures against this infection could be an effective measure in the future.


2017 ◽  
Vol 119 (4) ◽  
pp. 423-427 ◽  
Author(s):  
Débora de Mello Gonçales Sant’Ana ◽  
Marcelo Biondaro Gois ◽  
Catchia Hermes-Uliana ◽  
Letícia Sarturi Pereira-Severi ◽  
Emily Martins Baptista ◽  
...  

2021 ◽  
Vol 11 (21) ◽  
pp. 10436
Author(s):  
Taku Fukushima ◽  
Miho Takata ◽  
Ayano Kato ◽  
Takayuki Uchida ◽  
Takeshi Nikawa ◽  
...  

Exercise has beneficial effects on human health and is affected by two different pathways; motoneuron and endocrine. For the advancement of exercise research, in vitro exercise models are essential. We established two in vitro exercise models using C2C12 myotubes; EPS (electrical pulse stimulation) for a motoneuron model and clenbuterol, a specific β2 adrenergic receptor agonist, treatment for an endocrine model. For clenbuterol treatment, we found that Ppargc1a was induced only in low glucose media (1 mg/mL) using a 1-h treatment of 30 ng/mL clenbuterol. Global transcriptional changes of clenbuterol treatment were analyzed by RNA-seq and gene ontology analyses and indicated that mitogenesis and the PI3K-Akt pathway were enhanced, which is consistent with the effects of exercise. Cxcl1 and Cxcl5 were identified as candidate myokines induced by adrenaline. As for the EPS model, we compared 1 Hz of 1-pulse EPS and 1 Hz of 10-pulse EPS for 24 h and determined Myh gene expressions. Ten-pulse EPS induced higher Myh2 and Myh7 expression. Global transcriptional changes of 10-pulse EPS were also analyzed using RNA-seq, and gene ontology analyses indicated that CaMK signaling and hypertrophy pathways were enhanced, which is also consistent with the effects of exercise. In this paper, we provided two transcriptome results of in vitro exercise models and these databases will contribute to advances in exercise research.


2020 ◽  
Author(s):  
Zelin Liu ◽  
Huiru Ding ◽  
Jianqi She ◽  
Chunhua Chen ◽  
Weiguang Zhang ◽  
...  

AbstractCircular RNAs (circRNAs) are involved in various biological processes and in disease pathogenesis. However, only a small number of functional circRNAs have been identified among hundreds of thousands of circRNA species, partly because most current methods are based on circular junction counts and overlook the fact that circRNA is formed from the host gene by back-splicing (BS). To distinguish between expression originating from BS and that from the host gene, we present DEBKS, a software program to streamline the discovery of differential BS between two rRNA-depleted RNA sequencing (RNA-seq) sample groups. By applying real and simulated data and employing RT-qPCR for validation, we demonstrate that DEBKS is efficient and accurate in detecting circRNAs with differential BS events between paired and unpaired sample groups. DEBKS is available at https://github.com/yangence/DEBKS as open-source software.


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