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16 Publications visible to you, out of a total of 16
Evaluating sex-specific responses to western diet across the lifespan: impact on cardiac function and transcriptomic signatures in C57BL/6J mice at 530 and 640/750 days of age.

Abstract (Expand)

BACKGROUND: Long-term consumption of Western Diet (WD) is a well-established risk factor for the development of cardiovascular disease (CVD); however, there is a paucity of studies on the long-term … effects of WD on the pathophysiology of CVD and sex-specific responses. METHODS: Our study aimed to investigate the sex-specific pathophysiological changes in left ventricular (LV) function using transthoracic echocardiography (ECHO) and LV tissue transcriptomics in WD-fed C57BL/6 J mice for 125 days, starting at the age of 300 through 425 days. RESULTS: In female mice, consumption of the WD diet showed long-term effects on LV structure and possible development of HFpEF-like phenotype with compensatory cardiac structural changes later in life. In male mice, ECHO revealed the development of an HFrEF-like phenotype later in life without detectable structural alterations. The transcriptomic profile revealed a sex-associated dichotomy in LV structure and function. Specifically, at 530-day, WD-fed male mice exhibited differentially expressed genes (DEGs), which were overrepresented in pathways associated with endocrine function, signal transduction, and cardiomyopathies. At 750 days, WD-fed male mice exhibited dysregulation of several genes involved in various lipid, glucagon, and glutathione metabolic pathways. At 530 days, WD-fed female mice exhibited the most distinctive set of DEGs with an abundance of genes related to circadian rhythms. At 640 days, altered DEGs in WD-fed female mice were associated with cardiac energy metabolism and remodeling. CONCLUSIONS: Our study demonstrated distinct sex-specific and age-associated differences in cardiac structure, function, and transcriptome signature between WD-fed male and female mice.

Authors: A. Stepanyan, A. Brojakowska, R. Zakharyan, S. Hakobyan, S. Davitavyan, T. Sirunyan, G. Khachatryan, M. K. Khlgatian, M. Bisserier, S. Zhang, S. Sahoo, L. Hadri, A. Rai, V. N. S. Garikipati, A. Arakelyan, D. A. Goukassian

Date Published: 28th Dec 2024

Publication Type: Journal

PSF toolkit: an R package for pathway curation and topology-aware analysis.

Abstract (Expand)

Most high throughput genomic data analysis pipelines currently rely on over-representation or gene set enrichment analysis (ORA/GSEA) approaches for functional analysis. In contrast, topology-based … pathway analysis methods, which offer a more biologically informed perspective by incorporating interaction and topology information, have remained underutilized and inaccessible due to various limiting factors. These methods heavily rely on the quality of pathway topologies and often utilize predefined topologies from databases without assessing their correctness. To address these issues and make topology-aware pathway analysis more accessible and flexible, we introduce the PSF (Pathway Signal Flow) toolkit R package. Our toolkit integrates pathway curation and topology-based analysis, providing interactive and command-line tools that facilitate pathway importation, correction, and modification from diverse sources. This enables users to perform topology-based pathway signal flow analysis in both interactive and command-line modes. To showcase the toolkit's usability, we curated 36 KEGG signaling pathways and conducted several use-case studies, comparing our method with ORA and the topology-based signaling pathway impact analysis (SPIA) method. The results demonstrate that the algorithm can effectively identify ORA enriched pathways while providing more detailed branch-level information. Moreover, in contrast to the SPIA method, it offers the advantage of being cut-off free and less susceptible to the variability caused by selection thresholds. By combining pathway curation and topology-based analysis, the PSF toolkit enhances the quality, flexibility, and accessibility of topology-aware pathway analysis. Researchers can now easily import pathways from various sources, correct and modify them as needed, and perform detailed topology-based pathway signal flow analysis. In summary, our PSF toolkit offers an integrated solution that addresses the limitations of current topology-based pathway analysis methods. By providing interactive and command-line tools for pathway curation and topology-based analysis, we empower researchers to conduct comprehensive pathway analyses across a wide range of applications.

Authors: S. Hakobyan, A. Stepanyan, L. Nersisyan, H. Binder, A. Arakelyan

Date Published: 8th Sep 2023

Publication Type: Journal

PSF toolkit: an R package for pathway curation and topology-aware analysis

Abstract (Expand)

Most high throughput genomic data analysis pipelines currently rely on over-representation or gene set enrichment analysis (ORA/GSEA) approaches for functional analysis. In contrast, topology-based … pathway analysis methods, which offer a more biologically informed perspective by incorporating interaction and topology information, have remained underutilized and inaccessible due to various limiting factors. These methods heavily rely on the quality of pathway topologies and often utilize predefined topologies from databases without assessing their correctness. To address these issues and make topology-aware pathway analysis more accessible and flexible, we introduce the PSF (Pathway Signal Flow) toolkit R package. Our toolkit integrates pathway curation and topology-based analysis, providing interactive and command-line tools that facilitate pathway importation, correction, and modification from diverse sources. This enables users to perform topology-based pathway signal flow analysis in both interactive and command-line modes. To showcase the toolkit’s usability, we curated 36 KEGG signaling pathways and conducted several use-case studies, comparing our method with ORA and the topology-based signaling pathway impact analysis (SPIA) method. The results demonstrate that the algorithm can effectively identify ORA enriched pathways while providing more detailed branch-level information. Moreover, in contrast to the SPIA method, it offers the advantage of being cut-off free and less susceptible to the variability caused by selection thresholds. By combining pathway curation and topology-based analysis, the PSF toolkit enhances the quality, flexibility, and accessibility of topology-aware pathway analysis. Researchers can now easily import pathways from various sources, correct and modify them as needed, and perform detailed topology-based pathway signal flow analysis. In summary, our PSF toolkit offers an integrated solution that addresses the limitations of current topology-based pathway analysis methods. By providing interactive and command-line tools for pathway curation and topology-based analysis, we empower researchers to conduct comprehensive pathway analyses across a wide range of applications.

Authors: Siras Hakobyan, Ani Stepanyan, Lilit Nersisyan, Hans Binder, Arsen Arakelyan

Date Published: 23rd Aug 2023

Publication Type: Journal

Long-term environmental metal exposure is associated with hypomethylation of CpG sites in NFKB1 and other genes related to oncogenesis.

Abstract (Expand)

BACKGROUND: Long-term environmental exposure to metals leads to epigenetic changes and may increase risks to human health. The relationship between the type and level of metal exposure and epigenetic … changes in subjects exposed to high concentrations of metals in the environment is not yet clear. The aim of our study is to find the possible association of environmental long-term exposure to metals with DNA methylation changes of genes related to immune response and carcinogenesis. We investigated the association of plasma levels of 21 essential and non-essential metals detected by ICP-MS and the methylation level of 654 CpG sites located on NFKB1, CDKN2A, ESR1, APOA5, IGF2 and H19 genes assessed by targeted bisulfite sequencing in a cohort of 40 subjects living near metal mining area and 40 unexposed subjects. Linear regression was conducted to find differentially methylated positions with adjustment for gender, age, BMI class, smoking and metal concentration. RESULTS: In the metal-exposed group, five CpGs in the NFKB1 promoter region were hypomethylated compared to unexposed group. Four differentially methylated positions (DMPs) were associated with multiple metals, two of them are located on NFKB1 gene, and one each on CDKN2A gene and ESR1 gene. Two DMPs located on NFKB1 (chr4:102500951, associated with Be) and IGF2 (chr11:2134198, associated with U) are associated with specific metal levels. The methylation status of the seven CpGs located on NFKB1 (3), ESR1 (2) and CDKN2A (2) positively correlated with plasma levels of seven metals (As, Sb, Zn, Ni, U, I and Mn). CONCLUSIONS: Our study revealed methylation changes in NFKB1, CDKN2A, IGF2 and ESR1 genes in individuals with long-term human exposure to metals. Further studies are needed to clarify the effect of environmental metal exposure on epigenetic mechanisms and pathways involved.

Authors: A. Stepanyan, A. Petrackova, S. Hakobyan, J. Savara, S. Davitavyan, E. Kriegova, A. Arakelyan

Date Published: 7th Aug 2023

Publication Type: Journal

The radioenhancement potential of Schiff base derived copper (II) compounds against lung carcinoma in vitro.

Abstract (Expand)

For the last years, copper complexes have been intensively implicated in biomedical research as components of cancer treatment. Herewith, we provide highlights of the synthesis, physical measurements, … structural characterization of the newly developed Cu(II) chelates of Schiff Bases, Cu(Picolinyl-L-Tryptopahanate)2, Cu(Picolinyl-L-Tyrosinate)2, Cu(Isonicotinyl-L-Tyrosinate)2, Cu(Picolinyl-L-Phenylalaninate)2, Cu(Nicotinyl-L-Phenylalaninate)2, Cu(Isonicotinyl-L-Phenylalaninate)2, and their radioenhancement capacity at kV and MV ranges of irradiation of human lung carcinoma epithelial cells in vitro. The methods of cell growth, viability and proliferation were used. All compounds exerted very potent radioenhancer capacities in the irradiated lung carcinoma cells at both kV and MV ranges in a 100 μM concentration. At a concentration of 10 μM, only Cu(Picolinyl-L-Tyrosinate)2, Cu(Isonicotinyl-L-Tyrosinate)2, Cu(Picolinyl-L-Phenylalaninate)2 possessed radioenhancer properties at kV and MV ranges. Cu(Picolinyl-L-Tryptophanate)2 showed radioenhancer properties only at kV range. Cu(Nicotinyl-L-Phenylalaninate)2 and Cu(Isonicotinyl-L-Phenylalaninate)2 showed remarkable radioenhancer activity only at MV range. All compounds acted in dose-dependent manner at both tested energy ranges. These copper (II) compounds, in combination with 1 Gy irradiation at either 120 kV or 6 MV, are more efficient at delaying cell growth of lung cancer cells and at reducing cell viability in vitro than the irradiation administered alone. Thus, we have demonstrated that the studied copper compounds have a good potential for radioenhancement.

Authors: Gohar Tsakanova, Ani Stepanyan, Elina Arakelova, Violetta Ayvazyan, Vahan Tonoyan, Arsen Arakelyan, Guido Hildebrandt, Elisabeth Schültke

Date Published: 18th Jun 2021

Publication Type: Journal

SARS-CoV-2 detection by extraction-free qRT-PCR for massive and rapid COVID-19 diagnosis during a pandemic in Armenia

Abstract (Expand)

COVID-19 pandemic severely impacted the healthcare and economy on a global scale. It is widely recognized that mass testing is an efficient way to contain the spread of SARS-CoV-2 infection as well as … aid in the development of informed policies for disease management. However, the current COVID-19 worldwide infection rates increased the demand for rapid and reliable screening of infection. We compared the performance of qRT-PCR in direct heat-inactivated (H), heat-inactivated and pelleted (HC) samples against RNA in a group of 74 subjects (44 positive and 30 negative). Then we compared the sensitivity of HC in a larger group of 196 COVID-19 positive samples. Our study suggests that HC samples show higher accuracy for SARS-CoV-2 detection PCR assay compared to direct H (89 % vs 83 % of the detection in RNA). The sensitivity of detection using direct samples varied depending on the sample transport and storage media as well as the viral loads (as measured by qRT-PCR Ct levels). Altogether, all the data suggest that purified RNA provides more accurate results, however, direct sample testing with qRT-PCR may help to significantly increase testing capacity. Switching to the direct sample testing is justified if the number of tests is doubled at least.

Authors: Diana Avetyan, Andranik Chavushyan, Hovsep Ghazaryan, Ani Melkonyan, Ani Stepanyan, Roksana Zakharyan, Varduhi Hayrapetyan, Sofi Atshemyan, Gisane Khachatryan, Tamara Sirunyan, Suren Davitavyan, Gevorg Martirosyan, Gayane Melik-Andreasyan, Shushan Sargsyan, Armine Ghazazyan, Naira Aleksanyan, Xiushan Yin, Arsen Arakelyan

Date Published: 4th Jun 2021

Publication Type: Journal

Involvement of polymorphisms of the nerve growth factor and its receptor encoding genes in the etiopathogenesis of ischemic stroke

Abstract (Expand)

Background: Despite the important role of the nerve growth factor in the survival and maintenance of neurons in ischemic stroke, data regarding the relationships between variations in the encoding gene … and stroke are lacking. In the present study, we evaluated the association of the functional polymorphisms in NGF (rs6330) and NGFR (rs2072446 and rs734194) genes with ischemic stroke in an Armenian population. Methods: In total, 370 unrelated individuals of Armenian nationality were enrolled in this study. Genomic DNA samples of patients and healthy controls were genotyped using polymerase chain reaction with sequence-specific primers. Results: The results obtained indicate that the minor allele of rs6330 (Pcorr = 2.4E-10) and rs2072446 (Pcorr = 0.02) are significantly overrepresented in stroke group, while the minor allele of rs734194 (Pcorr = 8.5E-10) was underrepresented in diseased subjects. Single nucleotide polymorphisms in NGF gene (rs6330) and NGFR gene (rs2072446 and rs734194) are associated with the disease. Furthermore, it was shown that the carriage of the NGF rs6330*T minor allele is associated with increased infarct volume and higher risk of recurrent stroke. Conclusions: In conclusion, our findings suggest that the NGF rs6330*T and NGFR rs2072446*T minor alleles might be nominated as a risk factor for developing ischemic stroke and NGFR rs734194*G minor allele as a protective against this disease at least in Armenian population. Keywords: Ischemic stroke, Nerve growth factor, Nerve growth factor receptor, NGF, NGFR, Single nucleotide polymorphism

Authors: Ani Stepanyan, Roksana Zakharyan, Arsen Simonyan, Gohar Tsakanova, Arsen Arakelyan

Date Published: 2nd Mar 2018

Publication Type: Journal

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