Monitoring gene expression in muscle tissue of macaca fascicularis under the influence of testosterone and SARM

Author(s):  
Martina Reiter ◽  
Ales Tichopad ◽  
Irmgard Riedmaier ◽  
Michael W. Pfaffl ◽  
Heinrich H.D. Meyer

AbstractThe focus of this study was to evaluate data on the gene expression profiles induced by testosterone and a selective androgen receptor modulator (SARM, TAP Pharmaceutical Products Inc., Lake Forest, IL, USA) in androgen sensitive muscle tissue to obtain a better understanding on the molecular mechanisms of action and to identify biomarkers for SARM function in primate organs. A total of 24 male cyomolgus monkeys were divided into four groups: testosterone group, SARM1 group, SARM10 group, and control group, each consisting of six animals. The testosterone group was treated i.m. with 3.0 mg/kg Testostoviron

2020 ◽  
Vol 20 (12) ◽  
pp. 1487-1496 ◽  
Author(s):  
Midori Murakami ◽  
Hiroto Izumi ◽  
Tomoko Kurita ◽  
Chiho Koi ◽  
Yasuo Morimoto ◽  
...  

Background: Cisplatin is an important anticancer agent in cancer chemotherapy, but when resistant cells appear, treatment becomes difficult, and the prognosis is poor. Objective: In this study, we investigated the gene expression profile in cisplatin sensitive and resistant cells, and identified the genes involved in cisplatin resistance. Methods: Comparison of gene expression profiles revealed that UBE2L6 mRNA is highly expressed in resistant cells. To elucidate whether UBE2L6 is involved in the acquisition of cisplatin resistance, UBE2L6- overexpressing cells established from cisplatin-sensitive cells and UBE2L6-silenced cells developed from cisplatin- resistant cells were generated, and the sensitivity of cisplatin was examined. Results: The sensitivity of the UBE2L6-overexpressing cells did not change compared with the control cells, but the UBE2L6-silenced cells were sensitized to cisplatin. To elucidate the mechanism of UBE2L6 in cisplatin resistance, we compared the gene expression profiles of UBE2L6-silenced cells and control cells and found that the level of ABCB6 mRNA involved in cisplatin resistance was decreased. Moreover, ABCB6 promoter activity was partially suppressed in UBE2L6-silenced cells. Conclusion: These results suggest that cisplatin-resistant cells have upregulated UBE2L6 expression and contribute to cisplatin resistance by regulating ABCB6 expression at the transcriptional level. UBE2L6 might be a molecular target that overcomes cisplatin resistance.


2021 ◽  
Vol 14 (1) ◽  
pp. 41
Author(s):  
Hana Votavova ◽  
Zuzana Urbanova ◽  
David Kundrat ◽  
Michaela Dostalova Merkerova ◽  
Martin Vostry ◽  
...  

Deferasirox (DFX) is an oral iron chelator used to reduce iron overload (IO) caused by frequent blood cell transfusions in anemic myelodysplastic syndrome (MDS) patients. To study the molecular mechanisms by which DFX improves outcome in MDS, we analyzed the global gene expression in untreated MDS patients and those who were given DFX treatment. The gene expression profiles of bone marrow CD34+ cells were assessed by whole-genome microarrays. Initially, differentially expressed genes (DEGs) were determined between patients with normal ferritin levels and those with IO to address the effect of excessive iron on cellular pathways. These DEGs were annotated to Gene Ontology terms associated with cell cycle, apoptosis, adaptive immune response and protein folding and were enriched in cancer-related pathways. The deregulation of multiple cancer pathways in iron-overloaded patients suggests that IO is a cofactor favoring the progression of MDS. The DEGs between patients with IO and those treated with DFX were involved predominantly in biological processes related to the immune response and inflammation. These data indicate DFX modulates the immune response mainly via neutrophil-related genes. Suppression of negative regulators of blood cell differentiation essential for cell maturation and upregulation of heme metabolism observed in DFX-treated patients may contribute to the hematopoietic improvement.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Qing Xia ◽  
Xiangtian Ling ◽  
Zhonghao Wang ◽  
Tao Shen ◽  
Minghao Chen ◽  
...  

Abstract Purpose and background Recently, we found that maximal medial rectus recession and lateral rectus resection in patients with complete lateral rectus paralysis resulted in a partial restoration of abduction. In an attempt to understand some of the mechanisms involved with this effect we examined gene expression profiles of lateral recti from these patients, with our focus being directed to genes related to myogenesis. Materials and methods Lateral recti resected from patients with complete lateral rectus paralysis and those from concomitant esotropia (controls) were collected. Differences in gene expression profiles between these two groups were examined using microarray analysis and quantitative Reverse-transcription PCR (qRT-PCR). Results A total of 3056 differentially expressed genes (DEGs) were identified between these two groups. Within the paralytic esotropia group, 2081 genes were up-regulated and 975 down-regulated. The results of RT-PCR revealed that PAX7, MYOG, PITX1, SIX1 and SIX4 showed higher levels of expression, while that of MYOD a lower level of expression within the paralytic esotropia group as compared with that in the control group (p < 0.05). Conclusion The decreased expression of MYOD in the paralytic esotropia group suggested that extraocular muscle satellite cell (EOMSCs) differentiation processes were inhibited. Whereas the high expression levels of PAX7, SIX1/4 and MYOG, suggested that the EOMSCs were showing an effective potential for differentiation. The stimulation resulting from muscle surgery may induce EOMSCs to differentiate and thus restore abduction function.


2008 ◽  
Vol 180 (6) ◽  
pp. 2681-2687 ◽  
Author(s):  
Deborah R. Erickson ◽  
Steven R. Schwarze ◽  
Justin K. Dixon ◽  
Curtis J. Clark ◽  
Matt A. Hersh

Author(s):  
Zhenhua Dang ◽  
Yuanyuan Jia ◽  
Yunyun Tian ◽  
Jiabin Li ◽  
Yanan Zhang ◽  
...  

Organisms have evolved effective and distinct adaptive strategies to survive. Stipa grandis is one of the widespread dominant species on the typical steppe of the Inner Mongolian Plateau, and is regarded as a suitable species for studying the effects of grazing in this region. Although phenotypic (morphological and physiological) variations in S. grandis in response to long-term grazing have been identified, the molecular mechanisms underlying adaptations and plastic responses remain largely unknown. Accordingly, we performed a transcriptomic analysis to investigate changes in gene expression of S. grandis under four different grazing intensities. A total of 2,357 differentially expressed genes (DEGs) were identified among the tested grazing intensities, suggesting long-term grazing resulted in gene expression plasticity that affected diverse biological processes and metabolic pathways in S. grandis. DEGs were identified that indicated modulation of Calvin–Benson cycle and photorespiration metabolic pathways. The key gene´expression profiles encoding various proteins (e.g., Ribulose-1,5-bisphosphate carboxylase/oxygenase, fructose-1,6-bisphosphate aldolase, glycolate oxidase etc.) involved in these pathways suggest that they may synergistically respond to grazing to increase the resilience and stress tolerance of S. grandis. Our findings provide scientific clues for improving grassland use and protection, and identify important questions to address in future transcriptome studies.


2020 ◽  
Author(s):  
Hiroshi Honda ◽  
Norihisa Nishimichi ◽  
Michinori Yamashita ◽  
Yumiko Akimoto ◽  
Hirotoshi Tanimoto ◽  
...  

Abstract Background: Endometriosis, which affects up to 10% women of reproductive age, is defined by the presence of ectopic endometrial tissue outside the uterus. The current key drug of hormonal therapies for endometriosis is dienogest, which is a progestin with high specificity for the progesterone receptor. Although many findings about the anti-endometriotic effect of dienogest on endometriosis have been reported, the precise mechanisms of dienogest's anti-endometriotic effect remain unknown. Methods: To investigate the direct anti-endometriotic effect of dienogest on endometriotic cells, we determined and compared the genome-wide gene expression profiles of endometriotic stromal cells treated with dienogest (Dienogest group) and those not treated with dienogest (Control group) and then performed a pathway analysis using these data. To test the microarray data, we performed real-time RT-PCRs for matrix metallopeptidase (MMP)-1, MMP-3, MMP-10, and TIMP-4.Results: Six-hundred forty-seven genes were revealed to be differentially expressed between the Dienogest and Control groups. Of them, 314 genes were upregulated and 333 genes were downregulated in the Dienogest group compared to the Control group. We identified 20 canonical pathways that are significantly distinct in the Dienogest group versus the Control group. Among the 20 canonical pathways, MMPs including MMP-1, -3, and -10 were found to be the most involved genes. Conclusions: Our results suggest that dienogest may exert its anti-endometriotic effect through the direct suppression of MMPs.


2021 ◽  
Author(s):  
Hongpeng Fang ◽  
Zhansen Huang ◽  
Xianzi Zeng ◽  
Jiaming Wan ◽  
Jieying Wu ◽  
...  

Abstract Background As a common malignant cancer of the urinary system, the precise molecular mechanisms of bladder cancer remain to be illuminated. The purpose of this study was to identify core genes with prognostic value as potential oncogenes for the diagnosis, prognosis or novel therapeutic targets of bladder cancer. Methods The gene expression profiles GSE3167 and GSE7476 were available from the Gene Expression Omnibus (GEO) database. Next, PPI network was built to filter the hub gene through the STRING database and Cytoscape software and GEPIA and Kaplan-Meier plotter were implemented. Frequency and type of hub genes and sub groups analysis were performed in cBioportal and ULCAN database. Finally,We used RT-qPCR to confirm our results. Results Totally, 251 DEGs were excavated from two datasets in our study. We only founded high expression of SMC4, TYMS, CCNB1, CKS1B, NUSAP1 and KPNA2 was associated with worse outcomes in bladder cancer patients and no matter from the type of mutation or at the transcriptional level of hub genes, the tumor showed a high form of expression. However, only the expression of SMC4,CCNB1and CKS1B remained changed between the cancer and the normal samples in our results of RT-qPCR. Conclusion In conclusion,These findings indicate that the SMC4,CCNB1 and CKS1B may serve as critical biomarkers in the development and poor prognosis.


2021 ◽  
Author(s):  
Giulia Zancolli ◽  
Maarten Reijnders ◽  
Robert Waterhouse ◽  
Marc Robinson-Rechavi

Animals have repeatedly evolved specialized organs and anatomical structures to produce and deliver a cocktail of potent bioactive molecules to subdue prey or predators: venom. This makes it one of the most widespread convergent functions in the animal kingdom. Whether animals have adopted the same genetic toolkit to evolved venom systems is a fascinating question that still eludes us. Here, we performed the first comparative analysis of venom gland transcriptomes from 20 venomous species spanning the main Metazoan lineages, to test whether different animals have independently adopted similar molecular mechanisms to perform the same function. We found a strong convergence in gene expression profiles, with venom glands being more similar to each other than to any other tissue from the same species, and their differences closely mirroring the species phylogeny. Although venom glands secrete some of the fastest evolving molecules (toxins), their gene expression does not evolve faster than evolutionarily older tissues. We found 15 venom gland specific gene modules enriched in endoplasmic reticulum stress and unfolded protein response pathways, indicating that animals have independently adopted stress response mechanisms to cope with mass production of toxins. This, in turns, activates regulatory networks for epithelial development, cell turnover and maintenance which seem composed of both convergent and lineage-specific factors, possibly reflecting the different developmental origins of venom glands. This study represents the first step towards an understanding of the molecular mechanisms underlying the repeated evolution of one of the most successful adaptive traits in the animal kingdom.


2016 ◽  
Vol 2016 ◽  
pp. 1-15 ◽  
Author(s):  
Ben Holmes ◽  
Seung Ho Jung ◽  
Jing Lu ◽  
Jessica A. Wagner ◽  
Liudmilla Rubbi ◽  
...  

Transcranial direct current stimulation (tDCS) has been shown to modulate neuroplasticity. Beneficial effects are observed in patients with psychiatric disorders and enhancement of brain performance in healthy individuals has been observed following tDCS. However, few studies have attempted to elucidate the underlying molecular mechanisms of tDCS in the brain. This study was conducted to assess the impact of tDCS on gene expression within the rat cerebral cortex. Anodal tDCS was applied at 3 different intensities followed by RNA-sequencing and analysis. In each current intensity, approximately 1,000 genes demonstrated statistically significant differences compared to the sham group. A variety of functional pathways, biological processes, and molecular categories were found to be modified by tDCS. The impact of tDCS on gene expression was dependent on current intensity. Results show that inflammatory pathways, antidepressant-related pathways (GTP signaling, calcium ion binding, and transmembrane/signal peptide pathways), and receptor signaling pathways (serotonergic, adrenergic, GABAergic, dopaminergic, and glutamate) were most affected. Of the gene expression profiles induced by tDCS, some changes were observed across multiple current intensities while other changes were unique to a single stimulation intensity. This study demonstrates that tDCS can modify the expression profile of various genes in the cerebral cortex and that these tDCS-induced alterations are dependent on the current intensity applied.


2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Chenlei Zheng ◽  
Cheng Wang ◽  
Tan Zhang ◽  
Ding Li ◽  
Xiao-feng Ni ◽  
...  

Objective. Posttransplantation diabetes mellitus (PTDM) is a known complication of transplantation that affects the prognosis. Tacrolimus (Tac or FK506) is a widely used immunosuppressant that has been reported to be a risk factor for PTDM and to further induce complications in heart and skeletal muscles, but the mechanism is still largely unknown. In our preliminary experiments, we found that after Tac treatment, blood glucose increased, and the weight of skeletal muscle declined. Here, we hypothesize that tacrolimus can induce PTDM and influence the atrophy of skeletal muscle. Methods. We designed preliminary experiments to establish a tacrolimus-induced PTDM model. Gene expression profiles in quadriceps muscle from this rat model were characterized by oligonucleotide microarrays. Then, differences in gene expression profiles in muscle from PTDM rats that received tacrolimus and control subjects were analyzed by using GeneSpring GX 11.0 software (Agilent). Functional annotation and enrichment analysis of differentially expressed genes (DEGs) helped us identify clues for the side effects of tacrolimus. Results. Our experiments found that the quadriceps in tacrolimus-induced PTDM group were smaller than those in the control group. The study identified 275 DEGs that may be responsible for insulin resistance and the progression of PTDM, including 86 upregulated genes and 199 downregulated genes. GO and KEGG functional analysis of the DEGs showed a significant correlation between PTDM and muscle development. PPI network analysis screened eight hub genes and found that they were related to troponin and tropomyosin. Conclusions. This study explored the molecular mechanism of muscle atrophy in a tacrolimus-induced PTDM model by bioinformatics analyses. We identified 275 DEGs and identified significant biomarkers for predicting the development and progression of tacrolimus-induced PTDM.


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