Biochemical Phenomena, Metabolism, and Nutrition Commons^™

Adiposity Throughout Adulthood And Risk Of Young-Onset Breast Cancer Tumor Subtypes In The Young Women's Health History Study, Lydia Marcus Post, Dorothy R. Pathak, Ann S. Hamilton, Kelly A. Hirko, Richard T. Houang, Emily H. Guseman, Dan Sanfelippo, Nicole Bohme Carnegie, L. Karl Olson, Hallgeir Rui, Ann G. Schwartz, Ellen M. Velie

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

BACKGROUND: The role of adult adiposity in young-onset breast cancer (YOBC) subtype risk is not well understood.

METHODS: In this population-based case (n = 1812)-control (n = 1,381) study of invasive YOBC (ages <50 >years), cases were identified from the Los Angeles County and Metropolitan Detroit Surveillance, Epidemiology, and End Results registries, 2010 to 2015. Area-based, frequency-matched controls were sampled from the 2010 Census. General adiposity [body mass index (BMI)] and central adiposity (waist circumference and waist-to-height ratio) across adulthood and covariates were collected from in-person interviews and measurements. ORs and 95% confidence intervals (CI) for adiposity and YOBC tumor subtypes …

Random C-Peptide And Islet Antibodies At Onset Predict Β Cell Function Trajectory And Insulin Dependence In Pediatric Diabetes, Mustafa Tosur, Saima Deen, Xiaofan Huang, Serife Uysal, Marcela Astudillo, Richard A Oram, Maria J Redondo, Farook Jahoor, Ashok Balasubramanyam

Children’s Nutrition Research Center Staff Publications

Objective: Identification of prognostic biomarkers in pediatric diabetes is important for precision medicine. We assessed whether C-peptide and islet autoantibodies are useful to predict the natural history of children with new-onset diabetes.

Methods: We prospectively studied 72 children with new-onset diabetes (median follow-up: 8 months) by applying the Aβ classification system ("A+": islet autoantibody positive, "β+": random serum C-peptide ≥1.3 ng/mL at diagnosis). Beta-cell function was assessed longitudinally with 2 hours postprandial/stimulated urinary C-peptide-to-creatinine ratio (UCPCR) 3-12 weeks (V1) and 6 to 12 months after diagnosis (V2). We obtained a type 1 diabetes genetic risk score for each participant, and …

Are Prediction Models Moving Closer To Clinical Application In The Diagnosis Of Type Of Diabetes In Youth?, Fida Bacha

Children’s Nutrition Research Center Staff Publications

No abstract provided.

Relative Uptake Of Tomato Carotenoids By In Vitro Intestinal And Prostate Cancer Cells, Nancy E Moran, Brianna Alexander, Shivi Garg, Nathan Marchant, Noor A Hason

Children’s Nutrition Research Center Staff Publications

Background: Consumption of tomatoes and tomato carotenoids is associated with a reduced risk of prostate cancer. Prostate tissue accumulates tomato carotenoids, including lycopene, β-carotene, and phytoene. Phytoene accumulation is relatively greater in the prostate than that of lycopene, but the metabolic determinants of tissue carotenoid profiles are poorly understood.

Objectives: The purpose of this study was to determine if differences in stability, cellular uptake, and clearance of phytoene compared with lycopene or β-carotene by prostate and intestinal cells may explain differences in observed tissue carotenoid profiles.

Methods: Gene and protein expression for carotenoid metabolism in prostate cell lines were analyzed …

Associations Between Metabolic Disorders And Sjögren’S Disease, Chihiro Iwaya, Junichi Iwata

Faculty, Staff and Student Publications

Sjögren’s disease (SjD) is a systemic autoimmune disorder characterized by dry eyes and mouth caused by chronic inflammation and is often accompanied by various extra-glandular manifestations, including fatigue and diffuse pain. Although the pathogenesis of the disease remains elusive, several factors (e.g. environmental, genetic and hormonal factors, abnormal metabolic status) are associated with this condition. Accumulating evidence suggests a potential role of cholesterol metabolism in immune and non-immune modulation in various diseases. In this review, we summarize the current findings on the associations between cholesterol metabolism and SjD.

Mechanistic Diversity And Functional Roles Define The Substrate Specificity And Ligand Binding Of Bacterial Pgp Phosphatases, Wei Niu, Joanne Shi Woon Lam, Trung Vu, Guangwei Du, Hao Fan, Lei Zheng

Faculty, Staff and Student Publications

Phosphatidylglycerol is a critical membrane phospholipid in microorganisms, synthesized via the dephosphorylation of phosphatidylglycerol-phosphate (PGP) by three membrane-bound phosphatases: PgpA, PgpB, and PgpC. While any one of these enzymes can produce phosphatidylglycerol at WT levels, the reason for the presence of all three in bacteria remains unclear. To address this question, we characterized these phosphatases in vitro to uncover their mechanistic differences. Our assays demonstrated that all three enzymes catalyze the hydrolysis of PGP but exhibit distinct substrate selectivity. PgpB displays a broad substrate range, dephosphorylating various lipid phosphates, while PgpA and PgpC show a higher specificity for lysophosphatidic acid …

Hunting For Heroes: Brain Neurons Mediating Glp-1r Agonists In Obesity Treatment, Yuhan Cao, Qingchun Tong

Faculty, Staff and Student Publications

Glucagon-like peptide 1 (GLP-1) receptor agonists (GLP-1RAs) have proven to be highly effective in reducing obesity across species and ages, gaining unmet popularity in clinical treatments against obesity. Although extensive research efforts have been made to explore how the brain regulates body weight homeostasis including the effect brought up by GLP-1 and its synthetic analogs GLP-1RAs, the identity of neurons and neural pathways that are responsible for the observed anti-obesity effect of GLP-1RAs remain largely elusive. Excitingly, three recent high-profile studies presented compelling evidence that each argues for the importance of GLP-1Rs in the dorsomedial hypothalamus, hindbrain, or lateral septum, …

Targeting The Glutamine-Arginine-Proline Metabolism Axis In Cancer, Di Wang, Jiang-Jie Duan, Yu-Feng Guo, Jun-Jie Chen, Tian-Qing Chen, Jun Wang, Shi-Cang Yu

Faculty, Staff and Student Publications

Metabolic abnormalities are an important feature of tumours. The glutamine-arginine-proline axis is an important node of cancer metabolism and plays a major role in amino acid metabolism. This axis also acts as a scaffold for the synthesis of other nonessential amino acids and essential metabolites. In this paper, we briefly review (1) the glutamine addiction exhibited by tumour cells with accelerated glutamine transport and metabolism; (2) the methods regulating extracellular glutamine entry, intracellular glutamine synthesis and the fate of intracellular glutamine; (3) the glutamine, proline and arginine metabolic pathways and their interaction; and (4) the research progress in tumour therapy …

Mammalian Mitochondrial Inorganic Polyphosphate (Polyp) And Cell Signaling: Crosstalk Between Polyp And The Activity Of Ampk, Renata T. Da Costa, Anna Nichenko, Matheus M. Perez, Malgorzata Tokarska-Schlattner, Sheida Kavehmoghaddam, Vedangi Hambardikar, Ernest R. Scoma, Erin L. Seifert, Uwe Schlattner, Joshua C. Drake, Maria E. Solesio

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

UNLABELLED: Inorganic polyphosphate (polyP) is an evolutionary and ancient polymer composed by orthophosphate units linked by phosphoanhydride bonds. In mammalian cells, polyP shows a high localization in mammalian mitochondria, and its regulatory role in various aspects of bioenergetics has already been demonstrated, via molecular mechanism(s) yet to be fully elucidated. In recent years, a role for polyP in signal transduction, from brain physiology to the bloodstream, has also emerged.

OBJECTIVE: In this manuscript, we explored the intriguing possibility that the effects of polyP on signal transduction could be mechanistically linked to those exerted on bioenergetics.

METHODS: To conduct our studies, …

Validation Studies Of The Flash-Tv System To Passively Measure Children’S Tv Viewing, Anil Kumar Vadathya, Tatyana Garza, Uzair Alam, Alex Ho, Salma M A Musaad, Alicia Beltran, Jennette P Moreno, Tom Baranowski, Nimah Haidar, Sheryl O Hughes, Jason A Mendoza, Ashok Veeraraghavan, Joseph Young, Akane Sano, Teresia M O'Connor

Children’s Nutrition Research Center Staff Publications

TV viewing is associated with health risks, but existing measures of TV viewing are imprecise due to relying on self-report. We developed the Family Level Assessment of Screen use in the Home (FLASH)-TV, a machine learning pipeline with state-of-the-art computer vision methods to measure children's TV viewing. In three studies, lab pilot (n = 10), lab validation (n = 30), and home validation (n = 20), we tested the validity of FLASH-TV 3.0 in task-based protocols which included video observations of children for 60 min. To establish a gold-standard to compare FLASH-TV output, the videos were labeled by trained staff …

Fgf21 Acts In The Brain To Drive Macronutrient-Specific Changes In Behavioral Motivation And Brain Reward Signaling, Md Shahjalal H. Khan, Sora Q. Kim, Robert C. Ross, Florina Corpodean, Redin A. Spann, Diana A. Albarado, Sun O. Fernandez-Kim, Blaise Clarke, Hans Rudolf Berthoud, Heike Münzberg, David H. Mcdougal, Yanlin He, Sangho Yu, Vance L. Albaugh, Paul L. Soto, Christopher D. Morrison

School of Medicine Faculty Publications

Objective: Dietary protein restriction induces adaptive changes in food preference, increasing protein consumption over carbohydrates or fat. We investigated whether motivation and reward signaling underpin these preferences. Methods and Results: In an operant task, protein-restricted male mice responded more for liquid protein rewards, but not carbohydrate, fat, or sweet rewards compared to non-restricted mice. When the number of responses required to access protein reward varied, protein-restricted mice exhibited higher operant responses at moderate to high response requirements. The protein restriction-induced increase in operant responding for protein was absent in Fgf21-KO mice and mice with neuron-specific deletion of the FGF21 co-receptor …

The Impact Of Diabetes Mellitus On Hiv Virologic Control: Results Of The Macs/Wihs Combined Cohort Study, Sarah C Mann, Weiqun Tong, Alison G Abraham, Frank Palella, Anjali Sharma, Phyllis C Tien, Margaret A Fischl, Samy I Mcfarlane, Cecile D Lahiri, Susan Koletar, Daniel Merenstein, Michelle Floris-Moore, Jordan E Lake, Elizabeth Daubert, Aubri Hickman, Todd T Brown, Jose Castillo-Mancilla

Faculty, Staff and Student Publications

Objective: Diabetes mellitus (DM) is associated with lower antiretroviral (ART) drug exposure among persons with HIV (PWH) compared to PWH without DM. The association between DM and virologic control in PWH, however, remains unknown.

Methods: We included participants in the Multicenter AIDS Cohort Study/Women's Interagency HIV Study Combined Cohort Study (MWCCS) who had initiated ART between 1999 and 2020 and had a suppressed HIV viral load (≤200 copies/ml) within 1 year of ART initiation. We compared the frequency of incident HIV viremia (HIV-1 RNA >200 copies/ml) between adult PWH with and without DM. Poisson regression was used to examine the …

Observing The Impacts Of Different Diets On Clinical Outcomes In Patients With Alzheimer's Disease: A Scoping Review, Erjola Toska, Alessandra Ottley, Quinn Jackson, Rachel Fricker, Alexa Carleo, Gabriella Cutrali, Olivia D’Alessio, Raquel Rossman, Samuel Kruchakov, Abraham Edelstein, Lubov Nathanson

HCA-NSU MD Research Day

Observing the Impacts of Different Diets on Clinical Outcomes in patients with Alzheimer's disease: A Scoping Review Authors: Quinn Jackson, OMS-III; Rachel Fricker,OMS-III; Erjola Toska, OMS-III; Alessandra Ottley,OMS-III; Alexa Carleo,OMS-III; Gabriella Cutrali, OMS-III; Olivia D’Alessio, OMS-III; Raquel Rossman, OMS-III; Samuel Kruchakov, OMS-III; Abraham Edelstein,OMS-III; Lubov Nathanson, Ph.D. Program: Nova Southeastern University Dr. Kiran C. Patel College of Osteopathic Medicine, Florida Objectives: This study aimed to assess the literature published from 2013 to 2023 on the impact of diet on Alzheimer’s Disease (AD). Background: AD is primarily marked by β-amyloid plaques and neurofibrillary tangles, which impair neuronal synapses, leading to memory …

First Interim Results From Fine-Real: A Prospective, Non-Interventional, Phase 4 Study Providing Insights Into The Use And Safety Of Finerenone In A Routine Clinical Settingfirst Interim Results From Fine-Real: A Prospective, Non-Interventional, Phase 4 Study Providing Insights Into The Use And Safety Of Finerenone In A Routine Clinical Setting, Susanne B Nicholas, Ricardo Correa-Rotter, Nihar R Desai, Lixin Guo, Sankar D Navaneethan, Kevin M Pantalone, Christoph Wanner, Stefanie Hamacher, Samuel T Fatoba, Andrea Horvat-Broecker, Antonio Garreta-Rufas, Alain Gay, Martin Merz, David C Wheeler

Center for Medical Ethics and Health Policy Staff Publications

Background: Finerenone, a selective non-steroidal mineralocorticoid receptor antagonist, improves kidney and cardiovascular outcomes in patients with chronic kidney disease (CKD) associated with type 2 diabetes (T2D). The FINE-REAL study (NCT05348733) aims to evaluate the characteristics and treatment patterns of participants treated with finerenone in clinical practice.

Methods: FINE-REAL is a prospective, single-arm, non-interventional study of patients initiated on finerenone as part of their routine care in accordance with country-approved labels. The study, initiated in June 2022, is expected to be completed by January 2028. The cutoff for this pre-specified interim analysis was June 13, 2023.

Results: Participants were …

Fetal Sex Effects On Maternal Health Can Now Be Tested Via Randomization: A First-In-Class Illustration In Cows On Glucoregulatory Outcomes, Aridany Suarez-Trujillo, Colby J Vorland, Griffin T Nicholls, Daniella E Chusyd, Chelsie Parker, Lilian Golzarri-Arroyo, Sophia Swann, Bethany J Funnell, Kara R Stewart, David B Allison

Children’s Nutrition Research Center Staff Publications

Background: The maternal-offspring relationship, such as whether fetal sex influences maternal health, is essential to explore to advance prenatal and maternal health. While associations exist between fetal sex and maternal health outcomes, it is unclear whether these reflect a causal relationship.

Objective: To demonstrate that fetal sex can be randomly assigned to test the causal effect of fetal sex on maternal outcomes.

Methods: Holstein dairy cows were stratified and randomized using sealed opaque envelopes to be artificially inseminated with either X- or Y-sorted bull semen until 40 cows became pregnant. Monthly body weight measurements were recorded, and an intravenous glucose …

Avulsion Of The Flexor Digitorum Profundus Tendon During The Curettage Of A Recurrent Enchondroma: A Case Report, Shunpei Hama, Masataka Yasuda, Makoto Fukuda, Katsuaki Onishi, Takaaki Chikugo

Children’s Nutrition Research Center Staff Publications

Enchondroma rarely occurs in the distal phalanx, and avulsion of the flexor digitorum profundus (FDP) tendon in this area is also rare. We report a case of recurrent enchondroma in the distal phalanx, which required reconstruction for an accidental FDP avulsion during surgery. A 36-year-old right-handed woman visited our hospital with a suspected recurrence of enchondroma and a planned surgery. Radiographs and computed tomography revealed three translucent lesions in the distal phalanx of her left index finger. We performed curettage and calcium phosphate bone cement (CPC) grafting. During the procedure, an avulsion of the FDP tendon was found. We reattached …

Iridoid Glucosides Against Staphylococcus Aureus Infection And Inhibit Inflammation On Bovine Mammary Epithelial Cells, Yanfang Zhang, Ping Xu

The Thai Journal of Veterinary Medicine

Staphylococcus aureus can cause diseases in humans and livestock, destroy the body barrier, exacerbate inflammation, and seriously threaten human health and animal husbandry development. Iridoid glucosides isolated from Rehmannia glutinosa, is an important Chinese tradition medicine widely used in various diseases. The aim of this study was to investigate whether the iridoid glucosides was effective against S. aureus infection, and inhibits inflammation on bovine mammary epithelial cells. The antibacterial potential was determined using the in vitro broth microdilution assay against S. aureus. Then, the antibiofilm activity was tested by BCA protein assay, electric conductivity assay and scanning electron …

Hidden: A Baker's Dozen Ways In Which Research Reporting Is Less Transparent Than It Could Be And Suggestions For Implementing Einstein's Dictum, Abu Bakkar Siddique, Brian Shaw, Johanna Dwyer, David A Fields, Kevin Fontaine, David Hand, Randy Schekman, Jeffrey Alberts, Julie Locher, David B Allison

Children’s Nutrition Research Center Staff Publications

The tutelage of our mentors as scientists included the analogy that writing a good scientific paper was an exercise in storytelling that omitted unessential details that did not move the story forward or that detracted from the overall message. However, the advice to not get lost in the details had an important flaw. In science, it is the many details of the data themselves and the methods used to generate and analyze them that give conclusions their probative meaning. Facts may sometimes slow or distract from the clarity, tidiness, intrigue, or flow of the narrative, but nevertheless they are important …

Reproduction Has Immediate Effects On Female Mortality, But No Discernible Lasting Physiological Impacts: A Test Of The Disposable Soma Theory, Sharon E Mitchell, Megan Simpson, Lena Coulet, Solenn Gouedard, Catherine Hambly, Juliano Morimoto, David B Allison, John R Speakman

Children’s Nutrition Research Center Staff Publications

The disposable soma theory (DST) posits that organisms age and die because of a direct trade-off in resource allocation between reproduction and somatic maintenance. DST predicts that investments in reproduction accentuate somatic damage which increase senescence and shortens lifespan. Here, we directly tested DST predictions in breeding and nonbreeding female C57BL/6J mice. We measured reproductive outputs, body composition, daily energy expenditure, and oxidative stress at peak lactation and over lifetime. We found that reproduction had an immediate and negative effect on survival due to problems encountered during parturition for some females. However, there was no statistically significant residual effect on …

Predisposing, Enabling, And Need Factors Influencing Health-Related Quality Of Life Among People With Metabolic Syndrome, Olajide Adekunle, Yun Wang, Ismaeel Yunusa, Marc L. Fleming, Enrique Seoane-Vazquez, Lawrence M. Brown

Pharmacy Faculty Articles and Research

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