Multi-omics Analysis of Umbilical Cord Hematopoietic Stem Cells from a Multi-ethnic Cohort of Hawaii Reveals the Transgenerational Effect of Maternal Pre-Pregnancy Obesity.

Background: Maternal obesity is a health concern that may predispose newborns to a high risk of medical problems later in life. To understand the transgenerational effect of maternal obesity, we conducted a multi-omics study, using DNA methylation and gene expression in the CD34+/CD38-/Lin- umbilical cord blood hematopoietic stem cells (uHSCs) and metabolomics of the cord blood, all from a multi-ethnic cohort (n=72) from Kapiolani Medical Center for Women and Children in Honolulu, Hawaii (collected between 2016 and 2018).

Results: Differential methylation (DM) analysis unveiled a global hypermethylation pattern in the maternal pre-pregnancy obese group (BH adjusted p<0.

Atorvastatin lowers breast cancer risk by reversing an early tumorigenic signature.

Breast cancer remains a significant health challenge with complex molecular mechanisms. While many studies have explored genetic markers in breast carcinogenesis, few have studied the potential impact of pharmacological interventions such as Atorvastatin on its genetic landscape. This study aimed to elucidate the molecular distinctions between normal and tumor-adjacent tissues in breast cancer and to investigate the potential protective role of atorvastatin, primarily known for its lipid-lowering effects, against breast cancer.

Interactive Effects of Empagliflozin and Hyperglycemia on Urinary Amino Acids in Individuals With Type 1 Diabetes.

Optimizing energy use in the kidney is critical for normal kidney function. Here, we investigate the effect of hyperglycemia and sodium-glucose cotransporter 2 (SGLT2) inhibition on urinary amino acid excretion in individuals with type 1 diabetes (T1D). The open-label ATIRMA trial assessed the impact of 8 weeks of 25 mg empagliflozin orally once per day in 40 normotensive normoalbuminuric young adults with T1D.

Severe preeclampsia is not associated with significant DNA methylation changes but cell proportion changes in the cord blood - caution on the importance of confounding adjustment.

Epigenome-wide DNA methylation analysis (EWAS) is an important approach to identify biomarkers for early disease detection and prognosis prediction, yet its results could be confounded by other factors such as cell-type heterogeneity and patient characteristics. In this study, we address the importance of confounding adjustment by examining DNA methylation patterns in cord blood exposed to severe preeclampsia (PE), a prevalent and potentially fatal pregnancy complication. Without such adjustment, a misleading global hypomethylation pattern is obtained.

SGLT2 inhibitors mitigate kidney tubular metabolic and mTORC1 perturbations in youth-onset type 2 diabetes.

The molecular mechanisms of sodium-glucose cotransporter-2 (SGLT2) inhibitors (SGLT2i) remain incompletely understood. Single-cell RNA sequencing and morphometric data were collected from research kidney biopsies donated by young persons with type 2 diabetes (T2D), aged 12 to 21 years, and healthy controls (HCs). Participants with T2D were obese and had higher estimated glomerular filtration rates and mesangial and glomerular volumes than HCs.

Precision nephrology identified tumor necrosis factor activation variability in minimal change disease and focal segmental glomerulosclerosis.

The diagnosis of nephrotic syndrome relies on clinical presentation and descriptive patterns of injury on kidney biopsies, but not specific to underlying pathobiology. Consequently, there are variable rates of progression and response to therapy within diagnoses. Here, an unbiased transcriptomic-driven approach was used to identify molecular pathways which are shared by subgroups of patients with either minimal change disease (MCD) or focal segmental glomerulosclerosis (FSGS).

Placentas delivered by pre-pregnant obese women have reduced abundance and diversity in the microbiome.

Maternal pre-pregnancy obesity may have an impact on both maternal and fetal health. We examined the microbiome recovered from placentas in a multi-ethnic maternal pre-pregnant obesity cohort, through an optimized microbiome protocol to enrich low bacterial biomass samples. We found that the microbiomes recovered from the placentas of obese pre-pregnant mothers are less abundant and less diverse when compared to those from mothers of normal pre-pregnancy weight.

Prepregnant Obesity of Mothers in a Multiethnic Cohort Is Associated with Cord Blood Metabolomic Changes in Offspring.

Maternal obesity has become a growing global health concern that may predispose the offspring to medical conditions later in life. However, the metabolic link between maternal prepregnant obesity and healthy offspring has not yet been fully elucidated. In this study, we conducted a case-control study using a coupled untargeted and targeted metabolomic approach from the newborn cord blood metabolomes associated with a matched maternal prepregnant obesity cohort of 28 cases and 29 controls.

Lilikoi: an R package for personalized pathway-based classification modeling using metabolomics data.

Lilikoi (the Hawaiian word for passion fruit) is a new and comprehensive R package for personalized pathway-based classification modeling using metabolomics data. Four basic modules are presented as the backbone of the package: feature mapping module, which standardizes the metabolite names provided by users and maps them to pathways; dimension transformation module, which transforms the metabolomic profiles to personalized pathway-based profiles using pathway deregulation scores; feature selection module, which helps to select the significant pathway features related to the disease phenotypes; and classification and prediction module, which offers various machine learning classification algorithms. The package is freely available under the GPLv3 license through the github repository at: https://github.