scholarly journals Altered neurogenic pathways in experimental rat models of ischemic cerebral stroke: A transcriptome based meta-analysis

2021 ◽  
Author(s):  
Syed Aasish Roshan ◽  
Gayathri Elangovan ◽  
Dharani Gunaseelan ◽  
Swaminathan K. Jayachandran ◽  
Mahesh Kandasamy ◽  
...  
Keyword(s):  
Interaction Analysis ◽  
Meta Analysis ◽  
Time Frame ◽  
Cerebral Stroke ◽  
Protein Protein Interaction ◽  
Gene Enrichment ◽  
Network Analyst ◽  
Stroke Group ◽  
Microarray Datasets ◽  
Early Stroke

Objectives: Promoting neurogenesis mediated recovery is one of the most sought after strategies in recovery after cerebral stroke. In this paper we elucidate how neurogenesis related genes are altered in the early stroke environment, to hint at potential pathways for therapeutic recovery. Materials and Methods: Around 97 microarray datasets derived from stroke affected rat brains were collected from NCBI-GEO. Datasets were normalized and subjected to a meta-analysis in Network Analyst to identify differentially expressed genes. Gene enrichment analyses were carried out using GSEA, and WebGestalt and results were visualized using Cytoscape Enrichment mapping. Results: Nearly 939 differentially expressing genes were identified in the cerebral stroke group. Among them, 30 neurogenesis related genes were identified through enrichment mapping analysis, and 35 genes through Protein-Protein Interaction analysis. Highest upregulated neurogenesis genes were found to be TSPO, GFAP, VIM, and TGFB1. The Highest Downregulated neurogenesis genes were found to be THY1, NR1D1, CDK5, STX1B, and NOG. Conclusions: Through this study, we have identified that during the acute time frame after stroke, the majority of the neurogenesis genes related to neural proliferation and neural differentiation are downregulated, while the majority of the genes related to neuronal migration were upregulated. A single or combined therapeutic approach against the identified dysregulated genes could greatly aid neural restoration and functional recovery during the postischemic stage.

scholarly journals Genome Wide Analysis Approach Suggests Chromosome 2 Locus to be Associated with Thiazide and Thiazide Like-Diuretics Blood Pressure Response

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Sonal Singh ◽  
Caitrin W. McDonough ◽  
Yan Gong ◽  
Kent R. Bailey ◽  
Eric Boerwinkle ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Protein Interaction ◽  
Interaction Analysis ◽  
Inositol Phosphate ◽  
Meta Analysis ◽  
Hypertensive Patients ◽  
Protein Protein Interaction ◽  
Genome Wide ◽  
A Genome ◽  
Β Blockers

AbstractChlorthalidone (CTD) is more potent than hydrochlorothiazide (HCTZ) in reducing blood pressure (BP) in hypertensive patients, though both are plagued with BP response variability. However, there is a void in the literature regarding the genetic determinants contributing to the variability observed in BP response to CTD. We performed a discovery genome wide association analysis of BP response post CTD treatment in African Americans (AA) and European Americans (EA) from the Pharmacogenomic Evaluation of Antihypertensive Responses-2 (PEAR-2) study and replication in an independent cohort of AA and EA treated with HCTZ from the PEAR study, followed by a race specific meta-analysis of the two studies. Successfully replicated SNPs were further validated in beta-blocker treated participants from PEAR-2 and PEAR for opposite direction of association. The replicated and validated signals were further evaluated by protein-protein interaction network analysis. An intronic SNP rs79237970 in the WDR92 (eQTL for PPP3R1) was significantly associated with better DBP response to CTD (p = 5.76 × 10−6, β = −15.75) in the AA cohort. This SNP further replicated in PEAR (p = 0.00046, β = −9.815) with a genome wide significant meta-analysis p-value of 8.49 × 10−9. This variant was further validated for opposite association in two β-blockers treated cohorts from PEAR-2 metoprolol (p = 9.9 × 10−3, β = 7.47) and PEAR atenolol (p = 0.04, β = 4.36) for association with DBP. Studies have implicated WDR92 in coronary artery damage. PPP3R1 is the regulatory subunit of the calcineurin complex. Use of calcineurin inhibitors is associated with HTN. Studies have also shown polymorphisms in PPP3R1 to be associated with ventricular hypertrophy in AA hypertensive patients. Protein-protein interaction analysis further identified important hypertension related pathways such as inositol phosphate-mediated signaling and calcineurin-NFAT signaling cascade as important biological process associated with PPP3R1 which further strengthen the potential importance of this signal. These data collectively suggest that WDR92 and PPP3R1 are novel candidates that may help explain the genetic underpinnings of BP response of thiazide and thiazide-like diuretics and help identify the patients better suited for thiazide and thiazide-like diuretics compared to β-blockers for improved BP management. This may further help advance personalized approaches to antihypertensive therapy.

scholarly journals Targeting AKT/mTOR and Bcl-2 for Autophagic and Apoptosis Cell Death in Lung Cancer: Novel Activity of a Polyphenol Compound

Antioxidants ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 534
Author(s):  
Sucharat Tungsukruthai ◽  
Onrapak Reamtong ◽  
Sittiruk Roytrakul ◽  
Suchada Sukrong ◽  
Chanida Vinayanwattikun ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Death ◽  
Cancer Cells ◽  
Proteomic Analysis ◽  
Interaction Analysis ◽  
Time Dependent ◽  
The Novel ◽  
Protein Protein Interaction ◽  
Autophagy Induction ◽  
Acidic Vesicle

Autophagic cell death (ACD) is an alternative death mechanism in resistant malignant cancer cells. In this study, we demonstrated how polyphenol stilbene compound PE5 exhibits potent ACD-promoting activity in lung cancer cells that may offer an opportunity for novel cancer treatment. Cell death caused by PE5 was found to be concomitant with dramatic autophagy induction, as indicated by acidic vesicle staining, autophagosome, and the LC3 conversion. We further confirmed that the main death induction caused by PE5 was via ACD, since the co-treatment with an autophagy inhibitor could reverse PE5-mediated cell death. Furthermore, the defined mechanism of action and upstream regulatory signals were identified using proteomic analysis. Time-dependent proteomic analysis showed that PE5 affected 2142 and 1996 proteins after 12 and 24 h of treatment, respectively. The crosstalk network comprising 128 proteins that control apoptosis and 25 proteins involved in autophagy was identified. Protein–protein interaction analysis further indicated that the induction of ACD was via AKT/mTOR and Bcl-2 suppression. Western blot analysis confirmed that the active forms of AKT, mTOR, and Bcl-2 were decreased in PE5-treated cells. Taken together, we demonstrated the novel mechanism of PE5 in shifting autophagy toward cell death induction by targeting AKT/mTOR and Bcl-2 suppression.

Cost-Effectiveness Study of the Extracorporeal Shock-Wave Lithotriptor

1990 ◽  
Vol 6 (4) ◽  
pp. 623-632 ◽  
Author(s):  
Evi E. Hatziandreu ◽  
Karen Carlson ◽  
Albert G. Mulley ◽  
Milton C. Weinstein
Keyword(s):  
Shock Wave ◽  
Cost Effectiveness ◽  
Meta Analysis ◽  
Time Frame ◽  
Upper Urinary Tract ◽  
Extracorporeal Shock Wave ◽  
Probability Estimates ◽  
Urinary Tract Stones ◽  
Ultrasonic Lithotripsy ◽  
Cost Effectiveness Study

AbstractWe performed a cost-effectiveness analysis to examine the relative efficacy and costs of percutaneous ultrasonic lithotripsy (PUL), extracorporeal shock-wave lithotripsy (ESWL), and surgery for the treatment of upper urinary tract stones. We developed a Markov model with 35 states, cycles of 3 months, and a time frame of 5 years. Probability estimates were derived from a meta-analysis of the published literature. For stones less than or equal to 2 cm, ESWL is preferred to PUL, since it prevents 2 additional days of morbidity and saves $440. For larger stones, PUL is preferable to ESWL, avoiding 4 more days of morbidity, and saving $722. Both ESWL and PUL were superior to surgery. Sensitivity analysis showed that the results are sensitive to ESWL efficacy rates, the stone recurrence rate, and the hospital component of the ESWL cost. Our analysis suggests that although ESWL is preferable, relatively small changes in the efficacy and cost can shift the preferred strategy; in addition, these findings underscore the need for more reliable data.

Protein–protein interaction analysis using an affinity peptide tag and hydrophilic polystyrene plate

2007 ◽  
Vol 128 (2) ◽  
pp. 354-361 ◽  
Author(s):  
Y KUMADA ◽  
C ZHAO ◽  
R ISHIMURA ◽  
H IMANAKA ◽  
K IMAMURA ◽  
...  
Keyword(s):  
Protein Interaction ◽  
Interaction Analysis ◽  
Protein Protein Interaction ◽  
Polystyrene Plate ◽  
Affinity Peptide ◽  
Peptide Tag
Sign in / Sign up

Export Citation Format

Share Document