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Article ; Online: Deciphering novel common gene signatures for rheumatoid arthritis and systemic lupus erythematosus by integrative analysis of transcriptomic profiles.

Neetu Tyagi / Kusum Mehla / Dinesh Gupta

PLoS ONE, Vol 18, Iss 3, p e

2023 Volume 0281637

Abstract: Rheumatoid Arthritis (RA) and Systemic Lupus Erythematosus (SLE) are the two highly prevalent debilitating and sometimes life-threatening systemic inflammatory autoimmune diseases. The etiology and pathogenesis of RA and SLE are interconnected in several ...

Abstract	Rheumatoid Arthritis (RA) and Systemic Lupus Erythematosus (SLE) are the two highly prevalent debilitating and sometimes life-threatening systemic inflammatory autoimmune diseases. The etiology and pathogenesis of RA and SLE are interconnected in several ways, with limited knowledge about the underlying molecular mechanisms. With the motivation to better understand shared biological mechanisms and determine novel therapeutic targets, we explored common molecular disease signatures by performing a meta-analysis of publicly available microarray gene expression datasets of RA and SLE. We performed an integrated, multi-cohort analysis of 1088 transcriptomic profiles from 14 independent studies to identify common gene signatures. We identified sixty-two genes common among RA and SLE, out of which fifty-nine genes (21 upregulated and 38 downregulated) had similar expression profiles in the diseases. However, antagonistic expression profiles were observed for ACVR2A, FAM135A, and MAPRE1 genes. Thirty genes common between RA and SLE were proposed as robust gene signatures, with persistent expression in all the studies and cell types. These gene signatures were found to be involved in innate as well as adaptive immune responses, bone development and growth. In conclusion, our analysis of multicohort and multiple microarray datasets would provide the basis for understanding the common mechanisms of pathogenesis and exploring these gene signatures for their diagnostic and therapeutic potential.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2023-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Natural selection plays a significant role in governing the codon usage bias in the novel SARS-CoV-2 variants of concern (VOC)

Neetu Tyagi / Rahila Sardar / Dinesh Gupta

PeerJ, Vol 10, p e

2022 Volume 13562

Abstract: The ongoing prevailing COVID-19 pandemic caused by SARS-CoV-2 is becoming one of the major global health concerns worldwide. The SARS-CoV-2 genome encodes spike (S) glycoprotein that plays a very crucial role in viral entry into the host cell via binding ...

Abstract	The ongoing prevailing COVID-19 pandemic caused by SARS-CoV-2 is becoming one of the major global health concerns worldwide. The SARS-CoV-2 genome encodes spike (S) glycoprotein that plays a very crucial role in viral entry into the host cell via binding of its receptor binding domain (RBD) to the host angiotensin converting enzyme 2 (ACE2) receptor. The continuously evolving SARS-CoV-2 genome results in more severe and transmissible variants characterized by the emergence of novel mutations called ‘variants of concern’ (VOC). The currently designated alpha, beta, gamma, delta and omicron VOC are the focus of this study due to their high transmissibility, increased virulence, and concerns for decreased effectiveness of the available vaccines. In VOC, the spike (S) gene and other non-structural protein mutations may affect the efficacies of the approved COVID-19 vaccines. To understand the diversity of SARS-CoV-2, several studies have been performed on a limited number of sequences. However, only a few studies have focused on codon usage bias (CUBs) pattern analysis of all the VOC strains. Therefore, to evaluate the evolutionary divergence of all VOC S-genes, we performed CUBs analysis on 300,354 sequences to understand the evolutionary relationship with its adaptation in different hosts, i.e., humans, bats, and pangolins. Base composition and RSCU analysis revealed the presence of 20 preferred AU-ended and 10 under-preferred GC-ended codons. In addition, CpG was found to be depleted, which may be attributable to the adaptive response by viruses to escape from the host defense process. Moreover, the ENC values revealed a higher bias in codon usage in the VOC S-gene. Further, the neutrality plot analysis demonstrated that S-genes analyzed in this study are under 83.93% influence of natural selection, suggesting its pivotal role in shaping the CUBs. The CUBs pattern of S-genes was found to be very similar among all the VOC strains. Interestingly, we observed that VOC strains followed a trend of antagonistic codon ...
Keywords	Codon usage bias ; Mutational pressure ; Natural selection ; Variants of concern (VOC) ; SARS-CoV-2 ; Medicine ; R ; Biology (General) ; QH301-705.5
Subject code	570 ; 572
Language	English
Publishing date	2022-06-01T00:00:00Z
Publisher	PeerJ Inc.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Method and validation of synaptosomal preparation for isolation of synaptic membrane proteins from rat brain

Pradip Kumar Kamat / Anuradha Kalani / Neetu Tyagi

MethodsX, Vol 1, Iss C, Pp 102-

2014 Volume 107

Abstract: The ability to isolate and observe molecular changes in protein composition and function at synapses is important in understanding the disease mechanisms. Because signal transmission is highly regulated by transient phosphorylation of neuronal proteins ... ...

Abstract	The ability to isolate and observe molecular changes in protein composition and function at synapses is important in understanding the disease mechanisms. Because signal transmission is highly regulated by transient phosphorylation of neuronal proteins at the synapse, preservation of this protein modification during synaptosome preparation is essential. Therefore, enriched preparations of synaptic particles called synaptosome are necessary to study synapse function. Because of insufficiency of ample sample for quantitative and qualitative analysis via old method, we applied some modifications that were resultant in high synapse yield. Interestingly, we found that modified methods produced more protein as well as more clear protein band on electrophoresis. Therefore, the modified procedure was better than the older method in effort to isolate more pure synapse protein for improved result outcome. To advance the method for our study, the following modifications were made to the regularly used protocols: • The pellet consisting of synaptosomes was cleaned two to three times in HEPES buffer containing proteases inhibitor and centrifuged at 12,000 × g for 15 min each. This step is highly essential to remove any contamination of sucrose-HEPES buffer and other organelle's which interfere with protein purification analysis. • Following this step, the synaptosome pellets were suspended in RIPA buffer (mixed with protease inhibitor and PMSF) along with 0.2% TritonX-100 and further centrifuged at 20,000 × g. • Further, the resulting pellet was discarded and suspended in RIPA buffer (mixed with protease inhibitor and PMSF) only. The sample was immediately used for protein estimation and protein electrophoresis.
Keywords	Brain ; Neurons ; Synapse protein ; Science ; Q
Subject code	500
Language	English
Publishing date	2014-01-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Method and validation of synaptosomal preparation for isolation of synaptic membrane proteins from rat brain

Kamat, Pradip Kumar / Anuradha Kalani / Neetu Tyagi

MethodsX. 2014, v. 1

2014

Abstract	The ability to isolate and observe molecular changes in protein composition and function at synapses is important in understanding the disease mechanisms. Because signal transmission is highly regulated by transient phosphorylation of neuronal proteins at the synapse, preservation of this protein modification during synaptosome preparation is essential. Therefore, enriched preparations of synaptic particles called synaptosome are necessary to study synapse function. Because of insufficiency of ample sample for quantitative and qualitative analysis via old method, we applied some modifications that were resultant in high synapse yield. Interestingly, we found that modified methods produced more protein as well as more clear protein band on electrophoresis. Therefore, the modified procedure was better than the older method in effort to isolate more pure synapse protein for improved result outcome.To advance the method for our study, the following modifications were made to the regularly used protocols:•The pellet consisting of synaptosomes was cleaned two to three times in HEPES buffer containing proteases inhibitor and centrifuged at 12,000×g for 15min each. This step is highly essential to remove any contamination of sucrose-HEPES buffer and other organelle's which interfere with protein purification analysis.•Following this step, the synaptosome pellets were suspended in RIPA buffer (mixed with protease inhibitor and PMSF) along with 0.2% TritonX-100 and further centrifuged at 20,000×g.•Further, the resulting pellet was discarded and suspended in RIPA buffer (mixed with protease inhibitor and PMSF) only. The sample was immediately used for protein estimation and protein electrophoresis.
Keywords	brain ; cleaning ; electrophoresis ; membrane proteins ; neurons ; pellets ; phosphorylation ; protein composition ; proteinase inhibitors ; proteinases ; protocols ; qualitative analysis ; rats ; synapse ; synaptosomes
Language	English
Size	p. 102-107.
Publishing place	Elsevier B.V.
Document type	Article
ISSN	2215-0161
DOI	10.1016/j.mex.2014.08.002
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Expression of CD71 by flow cytometry in acute leukemias

Amit Pande / Pranav Dorwal / Dharmendra Jain / Neetu Tyagi / Simmi Mehra / Ritesh Sachdev / Vimarsh Raina

Indian Journal of Pathology and Microbiology, Vol 59, Iss 3, Pp 310-

More often seen in acute myeloid leukemia

2016 Volume 313

Abstract: Background: CD71 is a marker that has been usually used for identifying dysplasia in the erythroid series. We have tried to evaluate the expression of CD71 in various types of acute leukemias. Materials and Methods: We studied 48 patients of acute ... ...

Abstract	Background: CD71 is a marker that has been usually used for identifying dysplasia in the erythroid series. We have tried to evaluate the expression of CD71 in various types of acute leukemias. Materials and Methods: We studied 48 patients of acute leukemia, of which 25 were acute myeloid leukemia (AML), 13 were precursor B-acute lymphoblastic leukemia (B-ALL), 8 were T-ALL, and 2 were mixed phenotype acute leukemia (T/myeloid) as per the WHO classification. Results: We found that the expression of CD71 was most prevalent in AMLs (84%), followed by T-ALL (50%) and least in B-ALL (30%). Conclusion: This finding clearly shows the higher expression of CD71 in AMLs compared to other common type of leukemias, such as B- and T-ALL. We suggest that the high expression of CD71 in AMLs could be used as a diagnostic marker and may also be used for minimal residual disease analysis after further studies in posttreatment scenario. This study is the first of its kind in the South Asian population.
Keywords	Acute leukemia ; acute lymphoblastic leukemia ; acute myeloid leukemia ; CD71 ; flow cytometry ; Pathology ; RB1-214 ; Medicine ; R ; Microbiology ; QR1-502 ; Science ; Q
Subject code	610
Language	English
Publishing date	2016-01-01T00:00:00Z
Publisher	Medknow Publications
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Exercise Mitigates Alcohol Induced Endoplasmic Reticulum Stress Mediated Cognitive Impairment through ATF6-Herp Signaling

Akash K. George / Jyotirmaya Behera / Kimberly E. Kelly / Nandan K. Mondal / Kennedy P. Richardson / Neetu Tyagi

Scientific Reports, Vol 8, Iss 1, Pp 1-

2018 Volume 16

Abstract: Abstract Chronic ethanol/alcohol (AL) dosing causes an elevation in homocysteine (Hcy) levels, which leads to the condition known as Hyperhomocysteinemia (HHcy). HHcy enhances oxidative stress and blood-brain-barrier (BBB) disruption through modulation ... ...

Abstract	Abstract Chronic ethanol/alcohol (AL) dosing causes an elevation in homocysteine (Hcy) levels, which leads to the condition known as Hyperhomocysteinemia (HHcy). HHcy enhances oxidative stress and blood-brain-barrier (BBB) disruption through modulation of endoplasmic reticulum (ER) stress; in part by epigenetic alternation, leading to cognitive impairment. Clinicians have recommended exercise as a therapy; however, its protective effect on cognitive functions has not been fully explored. The present study was designed to observe the protective effects of exercise (EX) against alcohol-induced epigenetic and molecular alterations leading to cerebrovascular dysfunction. Wild-type mice were subjected to AL administration (1.5 g/kg-bw) and subsequent treadmill EX for 12 weeks (5 day/week@7–11 m/min). AL affected mouse brain through increases in oxidative and ER stress markers, SAHH and DNMTs alternation, while decreases in CBS, CSE, MTHFR, tight-junction proteins and cellular H2S levels. Mechanistic study revealed that AL increased epigenetic DNA hypomethylation of Herp promoter. BBB dysfunction and cognitive impairment were observed in the AL treated mice. AL mediated transcriptional changes were abolished by administration of ER stress inhibitor DTT. In conclusion, exercise restored Hcy and H2S to basal levels while ameliorating AL-induced ER stress, diminishing BBB dysfunction and improving cognitive function via ATF6-Herp-signaling. EX showed its protective efficacy against AL-induced neurotoxicity.
Keywords	Medicine ; R ; Science ; Q
Subject code	572
Language	English
Publishing date	2018-03-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Hydrogen Sulfide Promotes Bone Homeostasis by Balancing Inflammatory Cytokine Signaling in CBS-Deficient Mice through an Epigenetic Mechanism

Jyotirmaya Behera / Kimberly E. Kelly / Michael J. Voor / Naira Metreveli / Suresh C. Tyagi / Neetu Tyagi

Scientific Reports, Vol 8, Iss 1, Pp 1-

2018 Volume 16

Abstract: Abstract Previously, we have shown hyperhomocysteinemia (HHcy) to have a detrimental effect on bone remodeling, which is associated with osteoporosis. During transsulfuration, Hcy is metabolized into hydrogen sulfide (H2S), a gasotransmitter molecule ... ...

Abstract	Abstract Previously, we have shown hyperhomocysteinemia (HHcy) to have a detrimental effect on bone remodeling, which is associated with osteoporosis. During transsulfuration, Hcy is metabolized into hydrogen sulfide (H2S), a gasotransmitter molecule known to regulate bone formation. Therefore, in the present study, we examined whether H2S ameliorates HHcy induced epigenetic and molecular alterations leading to osteoporotic bone loss. To test this mechanism, we employed cystathionine-beta-synthase heterozygote knockout mice, fed with a methionine rich diet (CBS+/− +Met), supplemented with H2S-donor NaHS for 8 weeks. Treatment with NaHS, normalizes plasma H2S, and completely prevents trabecular bone loss in CBS+/− mice. Our data showed that HHcy caused inhibition of HDAC3 activity and subsequent inflammation by imbalancing redox homeostasis. The mechanistic study revealed that inflammatory cytokines (IL-6, TNF-α) are transcriptionally activated by an acetylated lysine residue in histone (H3K27ac) of chromatin by binding to its promoter and subsequently regulating gene expression. A blockade of HDAC3 inhibition in CBS+/− mice by HDAC activator ITSA-1, led to the remodeling of histone landscapes in the genome and thereby attenuated histone acetylation-dependent inflammatory signaling. We also confirmed that RUNX2 was sulfhydrated by administration of NaHS. Collectively, restoration of H2S may provide a novel treatment for CBS-deficiency induced metabolic osteoporosis.
Keywords	HDAC Activity ; Bone Marrow Mesenchymal Stem Cells (BMMSCs) ; BMMSCs Culture ; Bone Volume Per Tissue Volume (BV/TV) ; Total TRAP ; Medicine ; R ; Science ; Q
Subject code	616
Language	English
Publishing date	2018-10-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Hyperhomocysteinemia decreases bone blood flow

Neetu Tyagi / Thomas P Vacek / John T Fleming

Vascular Health and Risk Management, Vol 2011, Iss default, Pp 31-

2011 Volume 35

Abstract: Neetu Tyagi*, Thomas P Vacek*, John T Fleming, Jonathan C Vacek, Suresh C TyagiDepartment ...

Abstract	Neetu Tyagi, Thomas P Vacek, John T Fleming, Jonathan C Vacek, Suresh C TyagiDepartment of Physiology and Biophysics, School of Medicine, University of Louisville, Louisville, KY, USA *These authors have equal authorshipAbstract: Elevated plasma levels of homocysteine (Hcy), known as hyperhomocysteinemia (HHcy), are associated with osteoporosis. A decrease in bone blood flow is a potential cause of compromised bone mechanical properties. Therefore, we hypothesized that HHcy decreases bone blood flow and biomechanical properties. To test this hypothesis, male Sprague–Dawley rats were treated with Hcy (0.67 g/L) in drinking water for 8 weeks. Age-matched rats served as controls. At the end of the treatment period, the rats were anesthetized. Blood samples were collected from experimental or control rats. Biochemical turnover markers (body weight, Hcy, vitamin B12, and folate) were measured. Systolic blood pressure was measured from the right carotid artery. Tibia blood flow was measured by laser Doppler flow probe. The results indicated that Hcy levels were significantly higher in the Hcy-treated group than in control rats, whereas vitamin B12 levels were lower in the Hcy-treated group compared with control rats. There was no significant difference in folate concentration and blood pressure in Hcy-treated versus control rats. The tibial blood flow index of the control group was significantly higher (0.78 ± 0.09 flow unit) compared with the Hcy-treated group (0.51 ± 0.09). The tibial mass was 1.1 ± 0.1 g in the control group and 0.9 ± 0.1 in the Hcy-treated group. The tibia bone density was unchanged in Hcy-treated rats. These results suggest that Hcy causes a reduction in bone blood flow, which contributes to compromised bone biomechanical properties.Keywords: homocysteine, tibia, bone density
Keywords	Diseases of the circulatory (Cardiovascular) system ; RC666-701 ; Specialties of internal medicine ; RC581-951 ; Internal medicine ; RC31-1245 ; Medicine ; R ; DOAJ:Cardiovascular ; DOAJ:Medicine (General) ; DOAJ:Health Sciences
Subject code	630
Language	English
Publishing date	2011-01-01T00:00:00Z
Publisher	Dove Medical Press
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Blood flow interplays with elastin

Poulami Basu / Utpal Sen / Neetu Tyagi

Vascular Health and Risk Management, Vol 2010, Iss default, Pp 215-

collagen and MMP: TIMP ratios to maintain healthy vascular structure and function

2010 Volume 228

Abstract: Poulami Basu, Utpal Sen, Neetu Tyagi, Suresh C TyagiDepartment of Physiology and Biophysics ...

Abstract	Poulami Basu, Utpal Sen, Neetu Tyagi, Suresh C TyagiDepartment of Physiology and Biophysics, University of Louisville School of Medicine, Louisville, Kentucky, USAAbstract: Differential vascular remodeling is one of the major mechanisms of heterogeneity in atherosclerosis. The structural and functional heterogeneity between arteries and veins determines the degree of vascular remodeling. Matrix metalloproteases (MMPs) and their tissue inhibitors (TIMPs) play key roles in vascular structural and functional remodeling. We hypothesized that the level of blood flow in different arteries and veins caused structural and functional heterogeneity that ultimately determined potential vascular remodeling. To test this hypothesis, in vivo blood flow and blood pressure in the aorta, carotid, femoral artery, and femoral vein was measured in male Sprague-Dawley rats (weight 380–400 gm). Arterial and venous pressures were measured by PE-50 catheter cannulation. Blood flow was measured by a transonic ultrasound system. The aortic arch, femoral and carotid arteries, and abdominal vena cava were isolated to determine the expression of MMP-2, -9, -12, and -13 and TIMP-1, -3, and -4 by Western blot and in gelatin gel zymography. Masson trichrome and van Gieson stains were used to stain the histologic tissue sections. The results revealed that blood flow was higher in the aorta and carotid artery than the femoral artery and vein. MMP-9 and MMP-13 were higher in the carotid artery in comparison with the other blood vessels, while TIMP-3 showed higher expression in the aorta than the arteries. Further, the MMP-9 activity was significantly higher in the carotid artery than in the aorta and femoral artery. There was a higher degree of basement membrane collagen in the femoral artery and therefore a low elastin: collagen ratio, while in the carotid artery a higher level of elastin and, therefore, a high elastin: collagen ratio was found. The results suggested that medial thickness and elastin:collagen ratios had a threshold in blood flow in the range 0.6–2.5 mL/min, which increased robustly if blood flow increased to 2.7 mL/min. This pattern was inverted by the total MMP:TIMP ratio. We conclude that vascular remodeling is a function of rate of blood flow, which would in turn be determined by the amounts of MMPs and their inhibitors present. The study combined the endothelial and dynamic (blood flow/pressure) components that affect medial thickness and elastin: collagen ratios.Keywords: vascular remodeling, atherosclerosis, passive stretch-tension relationship
Keywords	Diseases of the circulatory (Cardiovascular) system ; RC666-701 ; Specialties of internal medicine ; RC581-951 ; Internal medicine ; RC31-1245 ; Medicine ; R ; DOAJ:Cardiovascular ; DOAJ:Medicine (General) ; DOAJ:Health Sciences
Subject code	610
Language	English
Publishing date	2010-03-01T00:00:00Z
Publisher	Dove Medical Press
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Mitochondrial division/mitophagy inhibitor (Mdivi) ameliorates pressure overload induced heart failure.

Srikanth Givvimani / Charu Munjal / Neetu Tyagi / Utpal Sen / Naira Metreveli / Suresh C Tyagi

PLoS ONE, Vol 7, Iss 3, p e

2012 Volume 32388

Abstract: We have previously reported the role of anti-angiogenic factors in inducing the transition from compensatory cardiac hypertrophy to heart failure and the significance of MMP-9 and TIMP-3 in promoting this process during pressure overload hemodynamic ... ...

Abstract	We have previously reported the role of anti-angiogenic factors in inducing the transition from compensatory cardiac hypertrophy to heart failure and the significance of MMP-9 and TIMP-3 in promoting this process during pressure overload hemodynamic stress. Several studies reported the evidence of cardiac autophagy, involving removal of cellular organelles like mitochondria (mitophagy), peroxisomes etc., in the pathogenesis of heart failure. However, little is known regarding the therapeutic role of mitochondrial division inhibitor (Mdivi) in the pressure overload induced heart failure. We hypothesize that treatment with mitochondrial division inhibitor (Mdivi) inhibits abnormal mitophagy in a pressure overload heart and thus ameliorates heart failure condition.To verify this, ascending aortic banding was done in wild type mice to create pressure overload induced heart failure and then treated with Mdivi and compared with vehicle treated controls.Expression of MMP-2, vascular endothelial growth factor, CD31, was increased, while expression of anti angiogenic factors like endostatin and angiostatin along with MMP-9, TIMP-3 was reduced in Mdivi treated AB 8 weeks mice compared to vehicle treated controls. Expression of mitophagy markers like LC3 and p62 was decreased in Mdivi treated mice compared to controls. Cardiac functional status assessed by echocardiography showed improvement and there is also a decrease in the deposition of fibrosis in Mdivi treated mice compared to controls.Above results suggest that Mdivi inhibits the abnormal cardiac mitophagy response during sustained pressure overload stress and propose the novel therapeutic role of Mdivi in ameliorating heart failure.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2012-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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