Biochemical Phenomena, Metabolism, and Nutrition Commons^™

Association Of Candidate Single-Nucleotide Polymorphism Genotypes With Plasma And Skin Carotenoid Concentrations In Adults Provided A Lycopene-Rich Juice, Anna C Norman, Daniel G Palmer, Nancy E Moran, James N Roemmich, Shanon L Casperson

Children’s Nutrition Research Center Staff Publications

Background: Carotenoids are fat-soluble phytochemicals with biological roles, including ultraviolet protective functions in skin. Spectroscopic skin carotenoid measurements can also serve as a noninvasive biomarker for carotenoid consumption. Single-nucleotide polymorphisms (SNPs) in metabolic genes are associated with human plasma carotenoid concentrations; however, their relationships with skin carotenoid concentrations are unknown.

Objectives: The objective of this study was to determine the relationship between 13 candidate SNPs with skin and plasma carotenoid concentrations before and after a carotenoid-rich tomato juice intervention.

Methods: In this randomized, controlled trial, participants (n = 80) were provided with lycopene-rich vegetable juice providing low (13.1 mg), medium …

Dose-Dependent Effects Of Dnmt3a In An Inducible Murine Model Of Krasg12d-Driven Leukemia, Jason H Rogers, Allison Rosen, Jaime M Reyes, Shamika Ketkar, Shannon E Conneely, Rohit Gupta, Luibin Yang, Matthew B Miller, Geraldo Medrano, Rogelio Aguilar, Nneka Uchenda, Margaret A Goodell, Rachel E Rau

Children’s Nutrition Research Center Staff Publications

DNMT3A mutations are frequently found in clonal hematopoiesis and a variety of hematologic malignancies including acute myeloid leukemia (AML). An assortment of mouse models have been engineered to explore the tumorigenic potential and malignant lineage bias due to loss of function of DNMT3A in consort with commonly co-mutated genes in myeloid malignancies such as Flt3, Nras, Kras, and c-Kit. We employed several tamoxifen-inducible Cre-ER^T2 murine model systems to study the effects of constitutively active Kras^G12D-driven myeloid leukemia (Kras) development together with heterozygous (3aHet) or homozygous Dnmt3a deletion (3aKO). Due to the rapid generation of …

Outcomes Of The Emdataresource Cryo-Em Ligand Modeling Challenge, Catherine L Lawson, Andriy Kryshtafovych, Grigore D Pintilie, Stephen K Burley, Jiří Černý, Vincent B Chen, Paul Emsley, Alberto Gobbi, Andrzej Joachimiak, Sigrid Noreng, Michael G Prisant, Randy J Read, Jane S Richardson, Alexis L Rohou, Bohdan Schneider, Benjamin D Sellers, Chenghua Shao, Elizabeth Sourial, Chris I Williams, Christopher J Williams, Ying Yang, Venkat Abbaraju, Pavel V Afonine, Matthew L Baker, Paul S Bond, Tom L Blundell, Tom Burnley, Arthur Campbell, Renzhi Cao, Jianlin Cheng, Grzegorz Chojnowski, K D Cowtan, Frank Dimaio, Reza Esmaeeli, Nabin Giri, Helmut Grubmüller, Soon Wen Hoh, Jie Hou, Corey F Hryc, Carola Hunte, Maxim Igaev, Agnel P Joseph, Wei-Chun Kao, Daisuke Kihara, Dilip Kumar, Lijun Lang, Sean Lin, Sai R Maddhuri Venkata Subramaniya, Sumit Mittal, Arup Mondal, Nigel W Moriarty, Andrew Muenks, Garib N Murshudov, Robert A Nicholls, Mateusz Olek, Colin M Palmer, Alberto Perez, Emmi Pohjolainen, Karunakar R Pothula, Christopher N Rowley, Daipayan Sarkar, Luisa U Schäfer, Christopher J Schlicksup, Gunnar F Schröder, Mrinal Shekhar, Dong Si, Abhishek Singharoy, Oleg V Sobolev, Genki Terashi, Andrea C Vaiana, Sundeep C Vedithi, Jacob Verburgt, Xiao Wang, Rangana Warshamanage, Martyn D Winn, Simone Weyand, Keitaro Yamashita, Minglei Zhao, Michael F Schmid, Helen M Berman, Wah Chiu

Children’s Nutrition Research Center Staff Publications

The EMDataResource Ligand Model Challenge aimed to assess the reliability and reproducibility of modeling ligands bound to protein and protein-nucleic acid complexes in cryogenic electron microscopy (cryo-EM) maps determined at near-atomic (1.9-2.5 Å) resolution. Three published maps were selected as targets: Escherichia coli beta-galactosidase with inhibitor, SARS-CoV-2 virus RNA-dependent RNA polymerase with covalently bound nucleotide analog and SARS-CoV-2 virus ion channel ORF3a with bound lipid. Sixty-one models were submitted from 17 independent research groups, each with supporting workflow details. The quality of submitted ligand models and surrounding atoms were analyzed by visual inspection and quantification of local map quality, model-to-map …

Personal Light Exposure Patterns And Incidence Of Type 2 Diabetes: Analysis Of 13 Million Hours Of Light Sensor Data And 670,000 Person-Years Of Prospective Observation, Daniel P Windred, Angus C Burns, Martin K Rutter, Chris Ho Ching Yeung, Jacqueline M Lane, Qian Xiao, Richa Saxena, Sean W Cain, Andrew J K Phillips

Faculty, Staff and Student Publications

BACKGROUND: Light at night disrupts circadian rhythms, and circadian disruption is a risk factor for type 2 diabetes. Whether personal light exposure predicts diabetes risk has not been demonstrated in a large prospective cohort. We therefore assessed whether personal light exposure patterns predicted risk of incident type 2 diabetes in UK Biobank participants, using ∼13 million hours of light sensor data.

METHODS: Participants (N = 84,790, age (M ± SD) = 62.3 ± 7.9 years, 58% female) wore light sensors for one week, recording day and night light exposure. Circadian amplitude and phase were modeled from weekly light data. Incident …

Cholesterol-Dependent Lxr Transcription Factor Activity Represses Pronociceptive Effects Of Estrogen In Sensory Neurons And Pain Induced By Myelin Basic Protein Fragments, Swathi K Hullugundi, Jennifer Dolkas, Andrei V Chernov, Tony L Yaksh, Kelly A Eddinger, Mila Angert, Glaucilene Ferreira Catroli, Alex Y Strongin, Patrick M Dougherty, Yan Li, Oswal Quehenberger, Aaron Armando, Veronica I Shubayev

Faculty, Staff and Student Publications

BACKGROUND: A bioactive myelin basic protein (MBP) fragment, comprising MBP

METHODS: In male and female normal and post-CCI rat sciatic nerves, we assessed: (i) cholesterol precursor and metabolite levels by lipidomics; (ii) MBP

RESULTS: CCI regulated LXRα ligand and receptor levels in nerves of both sexes, with cholesterol precursors, desmosterol and 7-DHC, and oxysterol elevated in females relative to males. MBP

CONCLUSION: The injury-released bioactive MBP fragments induce pronociceptive changes by selective inactivation of nuclear transcription factors, including LXRα. By Ncoa1 sequestration, bioactive MBP fragments render LXRα function to counteract pronociceptive activity of estrogen/ESR1 in sensory neurons. This effect of …

Long-Term Weight Loss Effects Of Semaglutide In Obesity Without Diabetes In The Select Trial, Donna H Ryan, Ildiko Lingvay, John Deanfield, Steven E Kahn, Eric Barros, Bartolome Burguera, Helen M Colhoun, Cintia Cercato, Dror Dicker, Deborah B Horn, G Kees Hovingh, Ole Kleist Jeppesen, Alexander Kokkinos, A Michael Lincoff, Sebastian M Meyhöfer, Tugce Kalayci Oral, Jorge Plutzky, André P Van Beek, John P H Wilding, Robert F Kushner

Faculty, Staff and Student Publications

In the SELECT cardiovascular outcomes trial, semaglutide showed a 20% reduction in major adverse cardiovascular events in 17,604 adults with preexisting cardiovascular disease, overweight or obesity, without diabetes. Here in this prespecified analysis, we examined effects of semaglutide on weight and anthropometric outcomes, safety and tolerability by baseline body mass index (BMI). In patients treated with semaglutide, weight loss continued over 65 weeks and was sustained for up to 4 years. At 208 weeks, semaglutide was associated with mean reduction in weight (-10.2%), waist circumference (-7.7 cm) and waist-to-height ratio (-6.9%) versus placebo (-1.5%, -1.3 cm and -1.0%, respectively; P < 0.0001 for all comparisons versus placebo). Clinically meaningful weight loss occurred in both sexes and all races, body sizes and regions. Semaglutide was associated with fewer serious adverse events. For each BMI category (

Protocol For Seahorse Analysis Of Ex Vivo Mouse Brown And White Adipose Tissues, Fenfen Wang, Phu M Huynh, Yu A An

Faculty, Staff and Student Publications

The mitochondrial stress test is a gold-standard approach for assessing adipose tissue physiological functions and pathological changes. Here, we present a protocol for conducting Seahorse assays using ex vivo mouse brown and white adipose depots. We describe steps for rehydrating the cartridge, preparing freshly harvested fat depots, placing them onto an islet capture plate, and incubating them in a non-CO2 incubator. We then detail procedures for adding mitochondrial stressor solutions and conducting the mitochondrial stress test using the Seahorse XFe24 Analyzer. For complete details on the use and execution of this protocol, please refer to An et al.1.

Mediterranean Diet Information On Tiktok And Implications For Digital Health Promotion Research: Social Media Content Analysis, Margaret Raber, Haley Allen, Sophia Huang, Maria Vazquez, Echo Warner, Debbe Thompson

Children’s Nutrition Research Center Staff Publications

Background: The Mediterranean diet has been linked to reduced risk for several cardiometabolic diseases. The lack of a clear definition of the Mediterranean diet in the scientific literature and the documented proliferation of nutrition misinformation on the internet suggest the potential for confusion among consumers seeking web-based Mediterranean diet information.

Objective: We conducted a social media content analysis of information about the Mediterranean diet on the influential social media platform, TikTok, to examine public discourse about the diet and identify potential areas of misinformation. We then analyzed these findings in the context of health promotion to identify potential challenges and …

Identification And Characterization Of Cannabichromene's Major Metabolite Following Incubation With Human Liver Microsomes, Alexandra M Ward, Touraj Shokati, Jost Klawitter, Jelena Klawitter, Vu Nguyen, Laura Kozell, Atheir I Abbas, David Jones, Uwe Christians

Faculty, Staff and Student Publications

Cannabichromene (CBC) is a minor cannabinoid within the array of over 120 cannabinoids identified in the Cannabis sativa plant. While CBC does not comprise a significant portion of whole plant material, it is available to the public in a purified and highly concentrated form. As minor cannabinoids become more popular due to their potential therapeutic properties, it becomes crucial to elucidate their metabolism in humans. Therefore, the goal of this was study to identify the major CBC phase I-oxidized metabolite generated in vitro following incubation with human liver microsomes. The novel metabolite structure was identified as 2′-hydroxycannabicitran using gas chromatography–mass …

Investigating The Association Between Metabolic Syndrome Conditions And Perinatal Mental Illness: A National Administrative Claims Study, Karishma Chhabria, Sudhakar Selvaraj, Jerrie Refuerzo, Chau Truong, Cecilia Ganduglia Cazaban

Faculty, Staff and Student Publications

BACKGROUND: Although the association between mental disorder and metabolic syndrome as a bidirectional relationship has been demonstrated, there is little knowledge of the cumulative and individual effect of these conditions on peripartum mental health. This study aims to investigate the association between metabolic syndrome conditions (MetS-C) and maternal mental illness in the perinatal period, while exploring time to incident mental disorder diagnosis in postpartum women.

METHODS: This observational study identified perinatal women continuously enrolled 1 year prior to and 1 year post-delivery using Optum's de-identified Clinformatics® Data Mart Database (CDM) from 2014 to 2019 with MetS-C i.e. obesity, diabetes, high …

Irx4204 Induces Senescence And Cell Death In Her2-Positive Breast Cancer And Synergizes With Anti-Her2 Therapy, Cassandra L Moyer, Amanda Lanier, Jing Qian, Darian Coleman, Jamal Hill, Vidyasagar Vuligonda, Martin E Sanders, Abhijit Mazumdar, Powel H Brown

Faculty, Staff and Student Publications

PURPOSE: Rexinoids, agonists of nuclear retinoid X receptor (RXR), have been used for the treatment of cancers and are well tolerated in both animals and humans. However, the usefulness of rexinoids in treatment of breast cancer remains unknown. This study examines the efficacy of IRX4204, a highly specific rexinoid, in breast cancer cell lines and preclinical models to identify a biomarker for response and potential mechanism of action.

EXPERIMENTAL DESIGN: IRX4204 effects on breast cancer cell growth and viability were determined using cell lines, syngeneic mouse models, and primary patient-derived xenograft (PDX) tumors. In vitro assays of cell cycle, apoptosis, …

Cyp3a Mediates An Unusual C(Sp2)-C(Sp3) Bond Cleavage Via Ipso-Addition Of Oxygen In Drug Metabolism, Xuan Qin, Yong Wang, Qiuji Ye, John M Hakenjos, Jin Wang, Mingxing Teng, Lei Guo, Zhi Tan, Damian W Young, Kevin R Mackenzie, Feng Li

Faculty, Staff and Students Publications

Mammalian cytochrome P450 drug-metabolizing enzymes rarely cleave carbon–carbon (C-C) bonds and the mechanisms of such cleavages are largely unknown. We identified two unusual cleavages of non-polar, unstrained C(sp2)-C(sp3) bonds in the FDA-approved tyrosine kinase inhibitor pexidartinib that are mediated by CYP3A4/5, the major human phase I drug metabolizing enzymes. Using a synthetic ketone, we rule out the Baeyer-Villiger oxidation mechanism that is commonly invoked to address P450-mediated C-C bond cleavages. Our studies in 18O2 and H218O enriched systems reveal two unusual distinct mechanisms of C-C bond cleavage: one bond is cleaved by CYP3A-mediated ipso-addition of oxygen to a C(sp2) …

The Role Of Skeletal Muscle Ampk/Mtorc1 Signaling In Disrupted Metabolism During Chemotherapy Treatment And Recovery, Jessica L. Halle

Alternative Theses and Dissertations (AETDs)

Colorectal cancer patient survival rate has increased over the past decade due to improved screening and treatment options. The clinically relevant FOLFOX (5-fluorouracil [5-FU], oxaliplatin, leucovorin) chemotherapy regimen is a mainstay treatment option, despite the development of severe side-effects that can occur acutely or develop as a late effect after treatment cessation. Cancer and chemotherapy can promote systemic metabolic dysfunction; consequently, patients will likely experience debilitating weakness and fatigue, and these symptoms are often accompanied by excessive fat and muscle loss. Although studies have established chemotherapy effects on the tumor, few have investigated mechanisms underlying the metabolic complications associated with …

The Association Of Self-Reported Sleep And Circadian Measures With Glycemic Control And Diabetes Complications Among Young Adults With Type 2 Diabetes, Dorit Koren, Kristen L Knutson, Brian K Burke, Kimberly L Drews, Fida Bacha, Lorraine Katz, Marsha D Marcus, Siripoom Mckay, Kristen Nadeau, Babak Mokhlesi, Today Study Group

Children’s Nutrition Research Center Staff Publications

We aim to examine the association of sleep duration, sleep quality, late chronotype, and circadian misalignment with glycemic control and risk of complications in young adults with youth-onset type 2 diabetes followed in the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study. Self-reported sleep duration, quality, timing, and circadian misalignment were assessed via a modified Pittsburgh Sleep Quality Index (PSQI) questionnaire, and chronotype was assessed via the Morningness-Eveningness Questionnaire (MEQ). We examined diabetes complications including loss of glycemic control (defined as hemoglobin A1c ≥8%), hypertension, dyslipidemia, albuminuria, and diabetic peripheral neuropathy. Multivariable logistic regression models were …

Development Of An Antioxidant-Rich Sugar-Free Plantain Candy And Assessment Of Its Shelf Life In A Flexible Laminate, Poulami Sarkar, Paramita Bhattacharjee, Bidhan Das

Faculty, Staff and Student Publications

RESEARCH BACKGROUND: Candy is a popular confection worldwide, and it would be beneficial to society if it were converted into a source of antioxidant molecules to eliminate its adverse health effects. The amount of antioxidants available even in fruit candies is questionable due to the high thermal processing losses they undergo and the presence of various food additives. Plantains (

EXPERIMENTAL APPROACH: To accomplish the first objective, lyophilized plantain powder, sorbitol and mannitol were used as base materials with minimal additives under minimal processing conditions to reduce processing loss. Sensory, proximate, physicochemical and phytochemical properties, including the antioxidant synergy among …

Mesenchymal-Specific Alms1 Knockout In Mice Recapitulates Metabolic Features Of Alström Syndrome, Eleanor J Mckay, Ineke Luijten, Xiong Weng, Pablo B Martinez De Morentin, Elvira De Frutos González, Zhanguo Gao, Mikhail G Kolonin, Lora K Heisler, Robert K Semple

Faculty, Staff and Student Publications

OBJECTIVE: Alström Syndrome (AS), caused by biallelic ALMS1 mutations, includes obesity with disproportionately severe insulin resistant diabetes, dyslipidemia, and fatty liver. Prior studies suggest that hyperphagia is accounted for by loss of ALMS1 function in hypothalamic neurones, whereas disproportionate metabolic complications may be due to impaired adipose tissue expandability. We tested this by comparing the metabolic effects of global and mesenchymal stem cell (MSC)-specific Alms1 knockout.

METHODS: Global Alms1 knockout (KO) mice were generated by crossing floxed Alms1 and CAG-Cre mice. A Pdgfrα-Cre driver was used to abrogate Alms1 function selectively in MSCs and their descendants, including preadipocytes. We combined …

Metabolic Alterations And Cellular Responses To Β-Hydroxybutyrate Treatment In Breast Cancer Cells, Hadas Fulman-Levy, Raichel Cohen-Harazi, Bar Levi, Lital Argaev-Frenkel, Ifat Abramovich, Eyal Gottlieb, Sarah Hofmann, Igor Koman, Elimelech Nesher

Faculty, Staff and Student Publications

BACKGROUND: The ketogenic diet (KD), based on high fat (over 70% of daily calories), low carbohydrate, and adequate protein intake, has become popular due to its potential therapeutic benefits for several diseases including cancer. Under KD and starvation conditions, the lack of carbohydrates promotes the production of ketone bodies (KB) from fats by the liver as an alternative source of metabolic energy. KD and starvation may affect the metabolism in cancer cells, as well as tumor characteristics. The aim of this study is to evaluate the effect of KD conditions on a wide variety of aspects of breast cancer cells …

The Inform (International Framework For Rehabilitation Medics) Project To Strengthen The Medical Specialty, Man Hung, Himani Patel, Samantha Lee, Justin Nguyen, Amir Mohajeri

Faculty, Staff and Student Publications

(1) Background: This study examines vitamin D’s impact on dental caries to inform prevention strategies, given its critical role in bone and calcium regulation, vital for dental health. (2) Methods: Data from 18,683 participants of the National Health and Nutrition Examination Survey (NHANES) 2011–2016 were analyzed. NHANES collects U.S. population data through interviews, physical exams, and tests, including vitamin D levels and dental health assessed using both the decayed, missing, and filled teeth (DMFT) index and the presence of untreated dental caries. Vitamin D levels were measured according to serum 25(OH)D concentrations, and the analyses adjusted for confounders such as …

Comprehensive In Vitro And In Vivo Evaluation Of Therapeutic Potential Of Bacopa-Derived Asiatic Acid Against A Human Oral Pathogen Streptococcus Mutans, Rajendran Jeyasri, Pandiyan Muthuramalingam, Arumugam Priya, Rajaiah Alexpandi, N. R. Siva Shanmugam, Saminathan Nivetha, Hyunsuk Shin, Shunmugiah Karutha Pandian, Arumugam Veera Ravi, Manikandan Ramesh

Food for Health: Publications

Dental caries is a common human oral disease worldwide, caused by an acid-producing bacteria Streptococcus mutans. The use of synthetic drugs and antibiotics to prevent dental caries has been increasing, but this can lead to severe side effects. To solve this issue, developing and developed countries have resorted to herbal medicines as an alternative to synthetic drugs for the treatment and prevention of dental caries. Therefore, there is an urgent need for plant-derived products to treat such diseases. Bacopa monnieri, a well-documented medicinal plant, contains 52 phytocompounds, including the pentacyclic triterpenoid metabolite known as asiatic acid (ASTA). Hence, …

Feasibility Of Fit24, A Digital Diabetes Prevention Program For Hispanic Adolescents: Qualitative Evaluation Study, Erica G Soltero, Salma M Musaad, Teresia M O'Connor, Debbe Thompson, Keith Norris, Bettina M Beech

Faculty, Staff and Students Publications

BACKGROUND: Digital health interventions are promising for reaching and engaging high-risk youth in disease prevention opportunities; however, few digital prevention interventions have been developed for Hispanic youth, limiting our knowledge of these strategies among this population.

OBJECTIVE: This study qualitatively assessed the feasibility and acceptability of Fit24, a 12-week goal-setting intervention that uses a Fitbit watch (Fitbit Inc) and theoretically grounded SMS text messages to promote physical activity and sleep among Hispanic adolescents (aged between 14 and 16 years) with obesity.

METHODS: After completing the intervention, a subsample of youth (N=15) participated in an in-depth interview. We categorized the themes …