using-human-differentially-expressed-gene-lists-to-perform-downstream

Using Human Differentially Expressed Gene Lists to Perform Downstream Pathway Enrichment Analysis and Target Prioritization

This protocol outlines a multi-step computational pipeline for identifying potential therapeutic targets from RNA-sequencing data, including installation ...

Brigham Young University

Preeclampsia (PE) is a complex pregnancy-specific disorder characterized by hypertension, proteinuria, and systemic inflammation, posing significant risks to maternal and fetal health. This study investigates the role of growth arrest-specific protein 6 (Gas6) in PE pathogenesis using a rat model. Gas6 administration induces hallmark PE features, including hypertension, proteinuria, and significant alterations in placental gene expression. Transcriptomic analysis revealed changes in pathways related to extracellular matrix remodeling, interleukin signaling, and oxidative stress, highlighting their contribution to PE pathology. Key findings include the upregulation of Fam111a, linked to oxidative stress and DNA replication, and the downregulation of Clca4, associated with ion transport and cellular homeostasis. Protein-level validation through immunofluorescence confirmed these alterations, reinforcing their mechanistic roles in placental dysfunction. Enrichment analysis further identified significant disruptions in extracellular matrix organization and intercellular signaling. These results underscore the pivotal role of Gas6 in exacerbating placental oxidative stress and systemic inflammation. Importantly, therapeutic inhibition of the Gas6/AXL axis using small-molecule inhibitors mitigated PE-like symptoms, highlighting its potential as a therapeutic target. This study provides novel insights into the molecular underpinnings of Gas6-mediated placental dysfunction and supports the development of targeted therapies to improve PE outcomes.

Transcriptomic Insights into Gas6-Induced Placental Dysfunction: Gene Targets for Preeclampsia Therapy.

Evidence for obesity and vitamin D deficiency as components of a data phenotype for primary hyperparathyroidism (pHPT) is critical to understanding primary hyperparathyroidism. This study examined the association between vitamin D, body mass index (BMI), albumin total calcium, parathyroid hormone (PTH) and data from National Health and Nutrition Examination Survey (NHANES). Associations of 25-hydroxyvitamin D, albumin adjusted calcium, and BMI with elevated PTH were evaluated, with elevated PTH being defined as>9.02 pmol/l. Outcomes were PTH (pmol/l), 25-hydroxyvitamin D (nmol/l), albumin adjusted calcium (mmol/l), and BMI. A weighted multivariable logistic regression model estimated the associations. A total of 9740 survey respondents were included in the study, 3.5% had elevated PTH. Mean vitamin D level was 57.7 (SD=22.6) nmol/l and BMI was 28.6 (SD=6.5) kg/m2. A one unit increase in BMI was associated with higher odds of elevated PTH [adjusted odds ratio (aOR)=1.04; 95% confidence interval (CI): 1.02, 1.06] whereas a one unit increase in vitamin D (aOR=0.97; 95% CI: 0.96, 0.98) or calcium (aOR=0.51; 95% CI: 0.29, 0.89) had decreased odds of elevated PTH. Higher BMI and lower levels of 25-hydroxyvitamin D are components of the primary hyperparathyroidism data phenotype. A refined data phenotype may improve detection/management of pHPT.

Article	Year
Transcriptomic Insights into Gas6-Induced Placental Dysfunction: Gene Targets for Preeclampsia Therapy. Cells\| PubMed ID: 39996749	2025
Associations of Obesity, Vitamin D, Adjusted Total Calcium, and Parathyroid Hormone in US from NHANES. Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme\| PubMed ID: 40578598	2025

Ethan Frank

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