Biochemical Phenomena, Metabolism, and Nutrition Commons^™

Quality-Of-Care Measures For Cardio-Oncology: An Ic-Os And Acc Cardio-Oncology Leadership Council Perspective, Vijay U Rao, Anita Deswal, Daniel Lenihan, Susan Dent, Teresa Lopez-Fernandez, Alexander R Lyon, Ana Barac, Nicolas Palaskas, Ming Hui Chen, Hector R Villarraga, Diego Sadler, Courtney M Campbell, Kerry Skurka, Matt J Wagner, Matthias Totzeck, Kathryn J Ruddy, Paul Heidenreich, Randal Thomas, Daniel Addison, Sarju Ganatra, Richard Cheng, David Reeves, Arjun K Ghosh, Joerg Herrmann

Children’s Nutrition Research Center Staff Publications

This document serves as a perspective on quality assessments in the discipline of cardio-oncology. We aim to define the current landscape, identify needs for quality and outcome improvements, and propose a roadmap for establishing viable metrics to improve patient care. Specifically, this document: 1) addresses the current lack of measurable high-quality metrics in cardio-oncology and their implications; 2) highlights needs and topic-specific barriers; 3) illustrates the process and application of a measurable quality metric; and 4) provides a framework to demonstrate measurable value for the growing population of patients with cancer and cardiovascular diseases.

Demographic Clinical Trial Diversity Assessment Methods: Use Of Real-World Data, Hua Chen, Nnadozie Emechebe, Sudeep Karve, Leon Raskin, Jailene Leal, Ning Cheng, Wendy Sebby, Kim Ribeiro, Samuel Crawford

Children’s Nutrition Research Center Staff Publications

Diversity in clinical trials is defined by the inclusion of clinical trial participants from various demographic groups that are representative of the broader population impacted by a disease state. Diversity in clinical trials is critical in identifying potential differences in safety and efficacy of treatments across races, ethnicities, ages, sexes, or other variables. In the United States, clinical trial diversity is often benchmarked against US Census data, which may limit the representativeness of patient demographics in clinical trials. Disease-specific, demographic estimates from real-world data (RWD) can facilitate benchmarking of clinical trials, support trial enrollment and the development of trial diversity …

Effects Of Prebiotic Phytocompound Administration In Gestational Diabetic Dams And Its Influence On Offspring Cognitive Outcomes, Gayathri Jagadeesan, Tushar K Das, Jennifer M Mendoza, Ghalya Alrousan, Maria P Blasco-Conesa, Parimelazhagan Thangaraj, Bhanu Priya Ganesh

Faculty, Staff and Student Publications

Gestational diabetes mellitus (GD)-induced gut dysbiosis in pregnant mothers may increase the risk of cognitive impairment and neurological disorders in both the mother and offspring as they age. Restoring gut balance could improve cognitive outcomes for both. Despite advancements in GD treatment, side effects have increased, and long-term neurocognitive impacts on offspring born to GD mothers remain underexplored. This study uses a GD mouse model, inducing pancreatic dysfunction in 3-month-old pregnant C57BL/6J mice with Streptozotocin. The efficacy and mechanism of the prebiotic phytocompound green leaf extract (

Neighborhood Disadvantage And Inequities In Access To Preemptive And Living Kidney Transplantation, Brandon M Fairless, Oluwatunmise A Fawole, Duc T Nguyen, Ankona Banerjee, Kenneth J Nobleza, Abiodun O Oluyomi, Omar Rosales, Jayna M Dave, Elizabeth A Onugha

Children’s Nutrition Research Center Staff Publications

Key Points:

1. Pediatric patients residing in low-resource neighborhoods experienced lower rates of preemptive and living donor kidney transplantation.

2. Household-level factors (single-parent, non-English primary language, and receiving government assistance) may also affect the type of transplant received.

3. Area Deprivation Index scores offer an objective way to quantify neighborhood-level disadvantage and can enhance pretransplant screening.

Background: Living donor kidney transplant (LDKT) generally results in better outcomes than deceased donor kidney transplant (DDKT). Preemptive kidney transplant (KT) allows patients to bypass undergoing maintenance dialysis and is associated with improved patient and graft survival. Studies in the US pediatric population have shown racial-ethnic disparities …

Adipose Progenitor Cell-Derived Extracellular Vesicles Suppress Macrophage M1 Program To Alleviate Midlife Obesity, Qing Zhou, Jia Gao, Guorao Wu, Chenwei Wang, Yan Yang, Teng Huang, Yi Wang, Tiantian Yue, Zhichao Gao, Hao Xie, Fei Xiong, Ke Xiang, Tuying Yong, Wanguang Zhang, Tongtong Zhang, Wen Kong, Cai Chen, Shu Zhang, Qilin Yu, Xuemei Fan, Shiwei Liu, Yanjun Liu, Cong-Yi Wang

Children’s Nutrition Research Center Staff Publications

Among different age groups, middle-aged individuals are particularly susceptible to obesity, with a 22% higher risk of all-cause mortality. However, the underlying mechanisms remain unclear. In this study, we identify adipose progenitor cells (APCs) in the white adipose tissue (WAT) of middle-aged subjects as potential causes of midlife obesity. Specifically, the extracellular vesicles (EVs) derived from APCs display an impaired ability to mitigate the inflammaging of adipose tissue macrophages (ATMs) in middle-aged individuals. Mechanistically, these EVs, lacking miR-145-5p, fail to suppress the expression of L-selectin in ATMs, thereby facilitating their M1 program via the NF-κB signaling pathway. In contrast, EVs …

Exploring Profiles Of Fathers Integrating Food And Physical Activity Parenting Practices, John A Jimenez-Garcia, Louise C Mâsse, Robert L Newton, Salma M Musaad, Alicia Beltran, Teresia M O'Connor

Children’s Nutrition Research Center Staff Publications

Objective: This study aims to identify fathers' profiles integrating food parenting practices (FPP) and physical activity parenting practices (PAPP).

Design: We analysed cross-sectional data. The fathers completed the reduced FPP and PAPP item banks and socio-demographic and family dynamics (co-parenting and household responsibility) questionnaires. We identified fathers' profiles via latent profile analysis. We explored the influence of social determinants, child characteristics and family dynamics on fathers' profiles using multinomial logistic regression.

Setting: Online survey in the USA.

Participants: Fathers of 5-11-year-old children.

Results: We analysed data from 606 fathers (age = 38 ± 8·0; Hispanic = 37·5 %). Most fathers …

Genetic Associations With C-Peptide Levels Before Type 1 Diabetes Diagnosis In At-Risk Relatives, Taylor M Triolo, Hemang M Parikh, Mustafa Tosur, Lauric A Ferrat, Lu You, Peter A Gottlieb, Richard A Oram, Suna Onengut-Gumuscu, Jeffrey P Krischer, Stephen S Rich, Andrea K Steck, Maria J Redondo

Children’s Nutrition Research Center Staff Publications

Objective: We sought to determine whether the type 1 diabetes genetic risk score-2 (T1D-GRS2) and single nucleotide polymorphisms are associated with C-peptide preservation before type 1 diabetes diagnosis.

Methods: We conducted a retrospective analysis of 713 autoantibody-positive participants who developed type 1 diabetes in the TrialNet Pathway to Prevention Study who had T1DExomeChip data. We evaluated the relationships of 16 known single nucleotide polymorphisms and T1D-GRS2 with area under the curve (AUC) C-peptide levels during oral glucose tolerance tests conducted in the 9 months before diagnosis.

Results: Higher T1D-GRS2 was associated with lower C-peptide AUC in the 9 months before …

Unraveling Genetic Links Between Diabetes And Heart Failure-A Machine Learning Approach, Sunakhi Sahoo, Marzieh Ayati

Research Symposium

Background: Diabetic heart failure (DHF) is defined as a chronic and progressive disease which is associated with both diabetes and heart failure (HF). Even though there have been many developments in the knowledge of these diseases, there is still much to learn about the genetic crossovers between the two. In this study, we identified genes that are associated with diabetic heart failure and heart failure by using gene expression data from patients with DHF, HF, and a control group of patients who died of natural causes. We sought to identify genes that had altered expression levels which could possibly play …

Uca1 As A Key Regulator Of The Warburg Effect During Anoikis Resistance In Colorectal Cancer Metastasis, Ricardo Pequeno Bracho, Salique Hassan Shaham, Yamile Abuchard Anaya, Sophia Leslie, Kyle Doxtater, Subhash Chauhan, Bilal Hafeez, Tamer Oraby, Manish K. Tripathi

Research Symposium

Colorectal carcinoma (CRC) is the second leading cause of cancer-related mortality in the United States. While localized CRC has a 90% five-year survival rate, this drops sharply to 14% upon metastasis. Metastasis occurs in approximately 40–50% of CRC cases and requires cancer cells to acquire anoikis resistance—a critical adaptation allowing survival after detachment from the extracellular matrix, enabling migration and colonization of secondary sites. Understanding the molecular mechanisms driving anoikis resistance, particularly those linked to altered glucose metabolism, is essential for developing targeted therapies for metastatic CRC.

Cancer cells frequently exhibit the Warburg Effect, a metabolic adaptation favoring glycolysis over …

Cardiometabolic Benefits Of A Non-Industrialized-Type Diet Are Linked To Gut Microbiome Modulation, Fuyong Li, Anissa M. Armet, Katri Korpela, Junhong Liu, Rodrigo Margain Quevedo, Francesco Asnicar, Benjamin Seethaler, Tianna B. S. Rusnak, Janis L. Cole, Zhihong Zhang, Shuang Zhao, Adele Gagnon, Edward C. Deehan, Joao F. Mota, Jeffrey A. Bakal, Russell Greiner, Dan Knights, Nicola Segata, Stephan C. Bischoff, Laurie Mereu, Andrea M. Haqq, Catherine J. Field, Liang Li, Carla M. Prado, Jens Walter

Department of Food Science and Technology: Faculty Publications

Industrialization adversely affects the gut microbiome and predisposes individuals to chronic non-communicable diseases. We tested a microbiome restoration strategy comprising a diet that recapitulated key characteristics of non-industrialized dietary patterns (restore diet) and a bacterium rarely found in industrialized microbiomes (Limosilactobacillus reuteri) in a randomized controlled feeding trial in healthy Canadian adults. The restore diet, despite reducing gut microbiome diversity, enhanced the persistence of L. reuteri strain from rural Papua New Guinea (PB-W1) and redressed several microbiome features altered by industrialization. The diet also beneficially altered microbiota-derived plasma metabolites implicated in the etiology of chronic non-communicable diseases. Considerable …

Overexpression And Biophysical And Functional Characterization Of A Recombinant Fgf21, Phuc Phan, Jason Hoang, Thallapuranam Krishnaswamy Suresh Kumar

Chemistry & Biochemistry Faculty Publications and Presentations

Fibroblast growth factor 21 (FGF21) is an endocrine FGF that plays a vital role in regulating essential metabolic pathways. FGF21 increases glucose uptake by cells, promotes fatty acid oxidation, reduces blood glucose levels, and alleviates metabolic diseases. However, detailed studies on its stability and biophysical characteristics have not been reported. Herein, we present the overexpression, biophysical characterization, and metabolic activity of a soluble recombinant FGF21 (rFGF21). The far-UV circular dichroism spectra of rFGF21 show a negative trough at 215 nm, indicating that the protein’s backbone predominantly adopts a β sheet conformation. rFGF21 shows intrinsic tyrosine fluorescence at 305 nm. Thermal …

Insulin Clearance At Randomisation And In Response To Treatment In Youth With Type 2 Diabetes: A Secondary Analysis Of The Today Randomised Clinical Trial, Kristen J Nadeau, Silva A Arslanian, Fida Bacha, Sonia Caprio, Lily C Chao, Ryan Farrell, Kara S Hughan, Maria Rayas, Melinda Tung, Kaitlyn Cross, Laure El Ghormli

Children’s Nutrition Research Center Staff Publications

Aims/hypothesis: Insulin resistance and compensatory hyperinsulinaemia are core features leading to beta cell failure in youth-onset type 2 diabetes. Insulin clearance (IC) is also a key regulator of insulin concentrations, but few data exist on IC in youth-onset type 2 diabetes. In a secondary analysis of our Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) randomised clinical trial, we investigated potential sex-, race-, ethnicity- and treatment-related differences in IC in youth-onset type 2 diabetes and aimed to identify metabolic phenotypes associated with IC at baseline and in response to metformin, metformin plus a lifestyle intervention, and metformin …

Altered Thermal Preference By Preoptic Estrogen Receptor Alpha Neurons In Postpartum Females, Nan Zhang, Meng Yu, Qianru Zhao, Bing Feng, Yue Deng, Jonathan C Bean, Qingzhuo Liu, Benjamin P Eappen, Yang He, Kristine M Conde, Hailan Liu, Yongjie Yang, Longlong Tu, Mengjie Wang, Yongxiang Li, Na Yin, Hesong Liu, Junying Han, Darah Ave Threat, Nathan Xu, Taylor Smiley, Pingwen Xu, Lulu Chen, Tianshu Zeng, Yanlin He, Chunmei Wang

Faculty, Staff and Students Publications

OBJECTIVE: This study aims to investigate how reproductive experience (RE) alters thermal preference and thermoregulation in female mice, with a focus on estrogen receptor alpha (ERα)-expressing neurons in the preoptic area (POA).

METHODS: Thermal preference and body temperature were measured in female mice with and without RE, and virgin female mice with selective deletion of ERα from the POA (ERα

RESULTS: We showed that female mice prefer a cooler environment starting from late pregnancy and persisting long term postpartum. Female mice with RE (>4 weeks post-weaning) displayed lower body temperature and a lower thermal preferred temperature, and lost preference …

Oxidized Carbon Nanoparticles Enhance Cellular Energetics With Application To Injured Brain, Karthik Mouli, Anton V Liopo, Emily A Mchugh, Erica Underwood, Jing Zhao, Pramod K Dash, Anh T T Vo, Vikas H Malojirao, Muralidhar L Hegde, James M Tour, Paul J Derry, Thomas A Kent

Faculty, Staff and Student Publications

Pro-energetic effects of functionalized, oxidized carbon nanozymes (OCNs) are reported. OCNs, derived from harsh acid oxidation of single-wall carbon nanotubes or activated charcoal are previously shown to possess multiple nanozymatic activities including mimicking superoxide dismutase and catalyzing the oxidation of reduced nicotinamide adenine dinucleotide (NADH) to NAD+. These actions are predicted to generate a glycolytic shift and enhance mitochondrial energetics under impaired conditions. Impaired mitochondrial energy metabolism is increasingly recognized as an important facet of traumatic brain injury (TBI) pathophysiology and decreases the efficiency of electron transport chain (ETC)-coupled adenosine triphosphate (ATP) and NAD+ regeneration. In vitro, OCNs promote a …

Pskh1 Kinase Activity Is Differentially Modulated Via Allosteric Binding Of Ca2+ Sensor Proteins, Christopher R Horne, Toby A Dite, Samuel N Young, Lucy J Mather, Laura F Dagley, Jared L Johnson, Tomer M Yaron-Barir, Emily M Huntsman, Leonard A Daly, Dominic P Byrne, Antonia L Cadell, Boaz H Ng, Jumana Yousef, Dylan H Multari, Lianju Shen, Luke M Mcaloon, Gerard Manning, Mark A Febbraio, Anthony R Means, Lewis C Cantley, Maria C Tanzer, David R Croucher, Claire E Eyers, Patrick A Eyers, John W Scott, James M Murphy

Children’s Nutrition Research Center Staff Publications

Protein Serine Kinase H1 (PSKH1) was recently identified as a crucial factor in kidney development and is overexpressed in prostate, lung, and kidney cancers. However, little is known about PSKH1 regulatory mechanisms, leading to its classification as a “dark” kinase. Here, we used biochemistry and mass spectrometry to define PSKH1’s consensus substrate motif, protein interactors, and how interactors, including Ca2+ sensor proteins, promote or suppress activity. Intriguingly, despite the absence of a canonical Calmodulin binding motif, Ca2+-Calmodulin activated PSKH1 while, in contrast, the ER-resident Ca2+ sensor of the Cab45, Reticulocalbin, Erc55, Calumenin (CREC) family, Reticulocalbin-3, suppressed PSKH1 catalytic activity. In …

Regulating Chemoresistance And Cancer Stemness: The Cdh17-Yap Pathway In Distinct Cellular States Of Lung Cancer Ctc Clusters, Zujun Que, Dan Qi, Yun Yang, Wang Yao, Jiajun Liu, Yan Li, Yuanyuan Yu, Luyao Wang, Fangfei Li, Ge Zhang, Erxi Wu, Jianhui Tian

Children’s Nutrition Research Center Staff Publications

Background: Drug resistance in metastatic lung cancer significantly contributes to patient mortality. This study explores the role of circulating tumor cells (CTCs), the precursors to metastasis, in driving this resistance. We aim to delineate the unique biological traits of CTC clusters in lung cancer and elucidate the mechanisms underlying their resistance to chemotherapy.

Methods: We used an ultralow adsorption plate to establish a CTC suspension culture system. Comparisons between adherent and suspension cultures of CTC-TJH-01 cells were made via Cell Counting Kit-8 (CCK-8), western blot, immunofluorescence, and flow cytometry assays to evaluate cell proliferation, drug resistance, and cancer stemness. The …

Silencing Faf2 Mitigates Alcohol-Induced Hepatic Steatosis By Modulating Lipolysis And Pcsk9 Pathway, Nazmul Huda, Praveen Kusumanchi, Yanchao Jiang, Hui Gao, Themis Thoudam, Ge Zeng, Nicholas J. Skill, Zhaoli Sun, Suthat Liangpunsakul, Jing Ma, Zhihong Yang

School of Medicine Faculty Publications

BACKGROUND: Chronic alcohol consumption leads to lipid accumulation, oxidative stress, cellular damage, and inflammation in the liver, collectively referred to as alcohol-associated liver disease (ALD). FAF2/UBXD8/ETEA (Fas-associated factor 2) is a ubiquitin ligase adaptor protein that plays a crucial role in the ubiquitin-mediated degradation of misfolded proteins in the endoplasmic reticulum. A recent genome-wide association study indicated an association between FAF2 and ALD; however, the exact contribution of FAF2 to ALD pathogenesis remains unclear. METHODS: FAF2 was knocked down using AAV-delivered shRNA in C57/BL6 mice. Mice were subjected to a chronic-plus-single binge ethanol feeding (NIAAA) model. Nine hours after gavage, …

A Deep Learning-Based System For Automatic Detection Of Emesis With High Accuracy In Suncus Murinus, Zengbing Lu, Yimeng Qiao, Xiaofei Huang, Dexuan Cui, Julia Y H Liu, Man Piu Ngan, Luping Liu, Zhixin Huang, Zi-Tong Li, Lingqing Yang, Aleena Khalid, Yingyi Deng, Sze Wa Chan, Longlong Tu, John A Rudd

Children’s Nutrition Research Center Staff Publications

Quantifying emesis in Suncus murinus (S. murinus) has traditionally relied on direct observation or reviewing recorded behaviour, which are laborious, time-consuming processes that are susceptible to operator error. With rapid advancements in deep learning, automated animal behaviour quantification tools with high accuracy have emerged. In this study, we pioneere the use of both three-dimensional convolutional neural networks and self-attention mechanisms to develop the Automatic Emesis Detection (AED) tool for the quantification of emesis in S. murinus, achieving an overall accuracy of 98.92%. Specifically, we use motion-induced emesis videos as training datasets, with validation results demonstrating an accuracy of 99.42% for …

Red Meat Consumption And Hypertension: An Updated Review, Tara S Allen, Michael Najem, Alexis C Wood, Danielle J Lee, Lorena S Pacheco, Lori B Daniels, Matthew A Allison

Faculty, Staff and Students Publications

PURPOSE OF REVIEW: Hypertension (HTN) is a major risk factor for cardiovascular diseases (CVD). The global prevalence of HTN and related CVD mortality continues to rise. The development of HTN is influenced by genetic predisposition and modifiable risk factors, including diet. One area of ongoing debate is the relationship between red meat consumption and risk of HTN.

RECENT FINDINGS: Processed red meat has become increasingly implicated in the pathogenesis and morbidity of HTN, though randomized control trials comparing HTN-related outcomes associated with red meat subtypes have yielded heterogenous results. This review summarizes the existing relevant literature and highlights the methodological …

Antidiabetic Properties Of Prickly Pear (Opuntia Ficus-Indica) Fruit Extract, Kenzy Aidan Joseph Mckay

The Undergraduate Research Journal

Diabetes mellitus is a metabolic disorder that claims 1.5 million lives annually. Opuntia ficus-indica, commonly known as the prickly pear, has been commonly used in traditional folk medicine for its hypoglycemic properties. It has been claimed that it has antimicrobial and antioxidant properties as well. The plant is native to Mexico and is commonly found in the middle east and India and folk medicine from all of these areas have been using prickly pear medicinally for years. To test these claims an extract of locally sourced Opuntia ficus-indica was prepared using the flesh and seeds of the fruit. The …