Biochemical Phenomena, Metabolism, and Nutrition Commons^™

The Misalignment Of Incentives In Academic Publishing And Implications For Journal Reform, Jennifer S Trueblood, David B Allison, Sarahanne M Field, Ayelet Fishbach, Stefan D M Gaillard, Gerd Gigerenzer, William R Holmes, Stephan Lewandowsky, Dora Matzke, Mary C Murphy, Sebastian Musslick, Vencislav Popov, Adina L Roskies, Judith Ter Schure, Andrei R Teodorescu

Children’s Nutrition Research Center Staff Publications

For most researchers, academic publishing serves two goals that are often misaligned-knowledge dissemination and establishing scientific credentials. While both goals can encourage research with significant depth and scope, the latter can also pressure scholars to maximize publication metrics. Commercial publishing companies have capitalized on the centrality of publishing to the scientific enterprises of knowledge dissemination and academic recognition to extract large profits from academia by leveraging unpaid services from reviewers, creating financial barriers to research dissemination, and imposing substantial fees for open access. We present a set of perspectives exploring alternative models for communicating and disseminating scientific research. Acknowledging that …

Ion Suppression Correction And Normalization For Non-Targeted Metabolomics, Iqbal Mahmud, Bo Wei, Lucas Veillon, Lin Tan, Sara Martinez, Bao Tran, Alexander Raskind, Felice De Jong, Yiwei Liu, Jibin Ding, Yun Xiong, Wai-Kin Chan, Rehan Akbani, John N Weinstein, Chris Beecher, Philip L Lorenzi

Faculty, Staff and Student Publications

Ion suppression is a major problem in mass spectrometry (MS)-based metabolomics; it can dramatically decrease measurement accuracy, precision, and sensitivity. Here we report a method, the IROA TruQuant Workflow, that uses a stable isotope-labeled internal standard (IROA-IS) library plus companion algorithms to: 1) measure and correct for ion suppression, and 2) perform Dual MSTUS normalization of MS metabolomic data. We evaluate the method across ion chromatography (IC), hydrophilic interaction liquid chromatography (HILIC), and reversed-phase liquid chromatography (RPLC)-MS systems in both positive and negative ionization modes, with clean and unclean ion sources, and across different biological matrices. Across the broad range …

Multimorbidity And Peak Oxygen Uptake In Patients Undergoing Cardiac Rehabilitation, Pauline F. Gomes, Audry Chacin-Suarez, Sophie A. Miller, Karen M. Fischer, Thomas P. Olson

Einstein Health Papers

No abstract provided.

Prediction Models Of Basal Energy Expenditure In Children And Adolescents Across The Bmi Spectrum Based On Room Calorimetry: A Cross-Sectional Cohort Study, Maurice Puyau, Roman Shypailo, Nancy F Butte, Salma Musaad, Fida Bacha

Children’s Nutrition Research Center Staff Publications

Background: Existing equations for prediction of basal energy expenditure (BEE) may not be accurate in children with overweight or obesity (OW/OB).

Objectives: We aimed to develop BEE prediction equations applicable to children and adolescents across a wide BMI spectrum using gold standard room calorimetry.

Methods: We measured weight, height, waist and hip circumferences, body composition (DXA), and BEE (whole room calorimetry) in a cross-sectional cohort of 1155 healthy children, 5-19 years of age. 67% of the males and 51% of the females were classified as OW/OB. We applied multiple linear regression analyses to develop BEE prediction models for each sex. …

Serotonin Neurons Integrate Gaba And Dopamine Inputs To Regulate Meal Initiation, Kristine M Conde, Hueyzhong Wong, Shuzheng Fang, Yongxiang Li, Meng Yu, Yue Deng, Qingzhuo Liu, Xing Fang, Mengjie Wang, Yuhan Shi, Olivia Z Ginnard, Yuxue Yang, Longlong Tu, Hesong Liu, Hailan Liu, Na Yin, Jonathan C Bean, Junying Han, Megan E Burt, Sanika V Jossy, Yongjie Yang, Qingchun Tong, Benjamin R Arenkiel, Chunmei Wang, Yang He, Yong Xu

Children’s Nutrition Research Center Staff Publications

Obesity is a growing global health epidemic with limited orally administered therapeutics. Serotonin (5-HT) is one neurotransmitter which remains an excellent target for new weight-loss therapies, but a gap remains in understanding the mechanisms involved in 5-HT produced in the dorsal Raphe nucleus (DRN) and its involvement in meal initiation. Using an optogenetic feeding paradigm, we showed that the 5-HTDRN→arcuate nucleus (ARH) circuit plays a role in meal initiation. Incorporating electrophysiology and ChannelRhodopsin-2-Assisted Circuit Mapping, we demonstrated that 5-HTDRN neurons receive inhibitory input partially from GABAergic neurons in the DRN, and the 5-HT response can be enhanced by hunger. Additionally, …

Leptin Receptor Neurons In The Dorsomedial Hypothalamus Require Distinct Neuronal Subsets For Thermogenesis And Weight Loss, Marie Francois, Laura Kaiser, Yanlin He, Yong Xu, J Michael Salbaum, Sangho Yu, Christopher D Morrison, Hans-Rudolf Berthoud, Heike Münzberg

Children’s Nutrition Research Center Staff Publications

The dorsomedial hypothalamus (DMH) receives inputs from the preoptic area (POA), where ambient temperature mediates physiological adaptations of energy expenditure and food intake. Warm-activated POA neurons suppress energy expenditure via brown adipose tissue (BAT) projecting neurons in the dorsomedial hypothalamus/dorsal hypothalamic area (dDMH/DHA). Our earlier work identified leptin receptor (Lepr)-expressing, BAT-projecting dDMH/DHA neurons that mediate metabolic leptin effects. Yet, the neurotransmitter (glutamate or GABA) used by dDMH/DHALepr neurons remains unexplored and was investigated in this study using mice. We report that dDMH/DHALepr neurons represent equally glutamatergic and GABAergic neurons. Surprisingly, chemogenetic activation of glutamatergic and/or GABAergic dDMH/DHA neurons were capable …

Association Between Maternal Stress And Child Sleep Quality: A Nationwide Echo Prospective Cohort Study, Sarah Dee Geiger, Aruna Chandran, Marie L Churchill, Maxwell Mansolf, Cai Zhang, Salma Musaad, Courtney K Blackwell, Stephanie M Eick, Dana E Goin, Susan Korrick, Akram Alshawabkeh, Patricia A Brennan, Carrie V Breton, Jose F Cordero, Sean Deoni, Viren D'Sa, Anne L Dunlop, Amy J Elliott, Assiamira Ferrara, Arlene Keddie, Monique Lebourgeois, Kaja Z Lewinn, Daphne Koinis-Mitchell, Maristella Lucchini, Sara S Nozadi, Thomas O'Connor, Yeyi Zhu, Emily Zimmerman, Susan L Schantz

Children’s Nutrition Research Center Staff Publications

Background: Childhood sleep quality is associated with physical, cognitive, and behavioral health and predicts later sleep quality; it has many determinants, including developmental exposures.

Objectives: To examine associations between maternal stress during pregnancy and childhood sleep quality and determine whether postnatal stress mediates the association.

Method: Data from the Environmental Influences on Child Health Outcomes cohort were used. Perceived Stress Scale (PSS) T-scores were the exposure measure. Outcome measures were preschool Child Behavior Checklist (CBCL) sleep syndrome scale and Patient-Reported Outcomes Measurement Information System Sleep Disturbance Parent Proxy short form 4a (PSD4a) T-scores at ages 4-8 years. Linear mixed-effects regression …

In Vitro Hydrolysis Of Areca Nut Xenobiotics In Human Liver, Vincenzo Paolillo, Mahendran Jayakumar, Colton Sheperd, Andrew Tran, Stephanie Hoang, Nhu Dao, Parag Jain, Alan L Myers

Faculty, Staff and Student Publications

Areca nut (AN) is a substance of abuse consumed by millions worldwide, in spite of established oral and systemic toxicities associated with its use. Previous research demonstrates methyl ester alkaloids in the AN, such as arecoline and guvacoline, exhibit mood-altering and toxicological effects. Nonetheless, their metabolism has not been fully elucidated in humans. In the present study, an HPLC-UV bioanalytical method was developed to evaluate the hydrolytic kinetics and clearance rates of arecoline and guvacoline in human liver microsomes (HLM) and cytosol (HLC). The bioassay was capable of quantifying arecoline and guvacoline (and carboxylate metabolites arecaidine and guvacine, respectively) with …

The Adiponectin-Pparγ Axis In Hepatic Stellate Cells Regulates Liver Fibrosis, Shangang Zhao, Qingzhang Zhu, Wang-Hsin Lee, Jan-Bernd Funcke, Zhuzhen Zhang, May-Yun Wang, Qian Lin, Bianca Field, Xue-Nan Sun, Guannan Li, Mbolle Ekane, Toshiharu Onodera, Na Li, Yi Zhu, Christine M Kusminski, Terry D Hinds, Philipp E Scherer

Faculty, Staff and Students Publications

Hepatic stellate cells (HSCs) are key drivers of local fibrosis. Adiponectin, conventionally thought of as an adipokine, is also expressed in quiescent HSCs. However, the impact of its local expression on the progression of liver fibrosis remains unclear. We recently generated a transgenic mouse line (Lrat-rtTA) that expresses the doxycycline-responsive transcriptional activator rtTA under the control of the HSC-specific lecithin retinol acyltransferase (Lrat) promoter, which enables us to specifically and inducibly overexpress or eliminate genes in these cells. The inducible elimination of HSCs protects mice from methionine/choline-deficient (MCD) diet-induced liver fibrosis, confirming their causal involvement in fibrosis development. We generated …

Sex-Specific Astrocyte Regulation Of Spinal Motor Circuits By Nkx61, Navish A Bosquez Huerta, Zhung-Fu Lee, Eun-Ah Christine Song, Junsung Woo, Yi-Ting Cheng, Debosmita Sardar, Ozlem Sert, Ehson Maleki, Kwanha Yu, Ekin Su Akdemir, Kaitlyn Sanchez, Juyeon Jo, Matthew N Rasband, Hyun Kyoung Lee, Akdes Serin Harmanci, Benjamin Deneen

Faculty, Staff and Students Publications

Astrocytes exhibit diverse cellular and molecular properties across the central nervous system (CNS). Recent studies identified region-specific transcription factors (TF) that oversee these diverse properties; how sex differences intersect with region-specific transcriptional programs to regulate astrocyte function is unknown. Here, we show that the TF Nkx6.1 is specifically expressed in ventral astrocytes of the spinal cord and that its deletion results in sex-specific effects on astrocyte morphology. Astrocytes from males exhibit enhanced morphological complexity, accompanied by increased motor function and cholinergic synapses. In contrast, female astrocytes exhibit reduced complexity and no changes in motor function. Mechanistically, we found that Nkx6.1 …

The Association Between Thyroid Differentiation Score And Survival Outcomes In Papillary Thyroid Carcinoma, Jennifer R Wang, Mark E Zafereo, Maria E Cabanillas, Chia Chin Wu, Li Xu, Yaoyi Dai, Wenyi Wang, Stephen Y Lai, Ying Henderson, Lauren Erasmus, Michelle D Williams, Corinne Joshu, Debashree Ray

Faculty, Staff and Student Publications

Context: Thyroid differentiation score (TDS), calculated based on mRNA expression levels of 16 genes controlling thyroid metabolism and function, has been proposed as a measure to quantify differentiation in papillary thyroid carcinoma (PTC).

Objective: The objective of this study is to determine whether TDS is associated with survival outcomes across patient cohorts.

Methods: Two independent cohorts of patients with PTC were used: (1) The Cancer Genome Atlas (TCGA) thyroid cancer study (N = 372), (2) MD Anderson Cancer Center (MDACC) cohort (N = 111). The primary survival outcome of interest was progression-free interval (PFI). Association with overall survival (OS) was …

Research Progress And Clinical Translation Potential Of Coronary Atherosclerosis Diagnostic Markers From A Genomic Perspective, Hanxiang Liu, Yuchen Zhang, Yueyan Zhao, Yuzhen Li, Xiaofeng Zhang, Lingyu Bao, Rongkai Yan, Yixin Yang, Huixian Zhou, Jinming Zhang, Siyuan Song

Children’s Nutrition Research Center Staff Publications

Objective: Coronary atherosclerosis (CAD) is characterized by arterial intima lipid deposition, chronic inflammation, and fibrous tissue proliferation, leading to arterial wall thickening and lumen narrowing. As the primary cause of coronary heart disease and acute coronary syndrome, CAD significantly impacts global health. Recent genetic studies have demonstrated CAD's polygenic and multifactorial nature, providing molecular insights for early diagnosis and risk assessment. This review analyzes recent advances in CAD-related genetic markers and evaluates their diagnostic potential, focusing on their applications in diagnosis and risk stratification within precision medicine.

Methods: We conducted a systematic review of CAD genomic studies from PubMed and …

Sex Differences In Response To Diet Enriched With Glutathione Precursors In The Aging Heart, Aude Angelini, Grecia Garcia Marquez, Anna Malovannaya, Marta L Fiorotto, Alexander Saltzman, Antrix Jain, Joann Trial, George E Taffet, Katarzyna A Cieslik

Faculty, Staff and Students Publications

Common features of the aging heart are dysregulated metabolism, inflammation, and fibrosis. Elevated oxidative stress is another hallmark of cardiac aging that can exacerbate each of these conditions. We hypothesize that by increasing natural antioxidant levels (glutathione), we will improve cardiac function. Twenty-one-month-old mice were fed glycine and N-acetyl cysteine (GlyNAC; glutathione precursors)-supplemented or control diets for 12 weeks. Heart function was monitored longitudinally, and the exercise performance was determined at the end of the study. We found that the GlyNAC diet was beneficial for old male but not old female mice, leading to an increase of Ndufb8 expression (a …

A Β-Hydroxybutyrate Shunt Pathway Generates Anti-Obesity Ketone Metabolites, Maria Dolores Moya-Garzon, Mengjie Wang, Veronica L Li, Xuchao Lyu, Wei Wei, Alan Sheng-Hwa Tung, Steffen H Raun, Meng Zhao, Laetitia Coassolo, Hashim Islam, Barbara Oliveira, Yuqin Dai, Jan Spaas, Antonio Delgado-Gonzalez, Kenyi Donoso, Aurora Alvarez-Buylla, Francisco Franco-Montalban, Anudari Letian, Catherine P Ward, Lichao Liu, Katrin J Svensson, Emily L Goldberg, Christopher D Gardner, Jonathan P Little, Steven M Banik, Yong Xu, Jonathan Z Long

Children’s Nutrition Research Center Staff Publications

β-Hydroxybutyrate (BHB) is an abundant ketone body. To date, all known pathways of BHB metabolism involve the interconversion of BHB and primary energy intermediates. Here, we identify a previously undescribed BHB secondary metabolic pathway via CNDP2-dependent enzymatic conjugation of BHB and free amino acids. This BHB shunt pathway generates a family of anti-obesity ketone metabolites, the BHB-amino acids. Genetic ablation of CNDP2 in mice eliminates tissue amino acid BHB-ylation activity and reduces BHB-amino acid levels. The most abundant BHB-amino acid, BHB-Phe, is a ketosis-inducible congener of Lac-Phe that activates hypothalamic and brainstem neurons and suppresses feeding. Conversely, CNDP2-KO mice exhibit …

Severe Hypercalcemia Following Hip Joint Implantation Of Calcium Sulfate Antibiotic Beads: Case Series And Review Of Literature., Andrew P. Demidowich, Mahsa Motevalli, Kevin Yi, Atena Kamali, Kristine Batty, Kendall F. Moseley, Robert Raymond Buber, Mehdi Hashemipour`, Mihail Zilbermint

Journal of Community Hospital Internal Medicine Perspectives

Purpose: The diagnosis and management of hypercalcemia in hospitalized patients can be challenging. Hypercalcemia is often associated with significant morbidity and end-organ damage which may delay a patient’s recovery.

Methods: We report a case series of three patients who underwent orthopedic procedures with intraoperative placement of vancomycin-loaded calcium sulfate beads. Patients had no known history of malignancy or excess intake of calcium, vitamin A or vitamin D. Laboratory workup showed low parathyroid (PTH) levels and normal PTH-related peptide levels. The temporal nature of the non-PTH mediated hypercalcemia in relation to implantation of the antibiotic beads suggests causality of exogenous calcium …

Potentiation Of Gelonin Cytotoxicity By Pulsed Electric Fields, Olga N. Pakhomova, Eleni Zivla, Giedre Silkuniene, Mantas Silkunas, Andrei G. Pakhomov

Bioelectrics Publications

Gelonin is a ribosome-inactivating protein with extreme intracellular toxicity but poor permeation into cells. Targeted disruption of cell membranes to facilitate gelonin entry is explored for cancer and tissue ablation. We demonstrate a hundreds- to thousands-fold enhancement of gelonin cytotoxicity by pulsed electric fields in the T24, U-87, and CT26 cell lines. The effective gelonin concentration to kill 50% of cells (EC₅₀) after electroporation ranged from <1 nM to about 100 nM. For intact cells, the EC₅₀ was unattainable even at the highest gelonin concentration of 1000 nM, which reduced cell survival by only 5–15%. For isoeffective electroporation treatments using 300 ns, 9 µs, and 100 µs pulses, longer pulses were more efficient at lowering gelonin EC₅₀. Increasing the electric field strength of 8, 100 µs pulses from 0.65 to 1.25 kV/cm reduced gelonin EC₅₀ from 128 nM to 0.72 nM. Conversely, the presence of 100 nM gelonin enabled a more than 20-fold reduction in the number of pulses required for equivalent cell killing. Pulsed electric field-mediated delivery of gelonin shows promise for hyperplasia ablation at concentrations sufficiently low to minimize or avoid systemic toxicity.

Microbial Remodeling Of Gut Tryptophan Metabolism And Indole-3-Lactate Production Regulate Epithelial Barrier Repair And Viral Suppression In Human And Simian Immunodeficiency Virus Infections, Clarissa Santos Rocha, Katie L. Alexander, Carolina Herrera, Mariana G. Weber, Irina Grishina, Lauren A. Hirao, Dylan J. Kramer, Juan Arredondo, Abigail Mende, Katti R. Crakes, Anne N. Fenton, Maria L. Marco, David A. Mills, John C. Kappes, Lesley E. Smythies, Paul Ziprin, Sumathi Sankaran-Walters, Phillip D. Smith, Satya Dandekar

Department of Obstetrics & Gynecology Faculty Publications

Gut inflammatory diseases cause microbial dysbiosis. Human immunodeficiency virus-1 (HIV) infection disrupts intestinal integrity, subverts repair/renewal pathways, impairs mucosal immunity and propels microbial dysbiosis. However, microbial metabolic mechanisms driving repair mechanisms in virally inflamed gut are not well understood. We investigated the capability and mechanisms of gut microbes to restore epithelial barriers and mucosal immunity in virally inflamed gut by using a multipronged approach: an in vivo simian immunodeficiency virus (SIV)-infected nonhuman primate model of HIV/AIDS, ex vivo HIV-exposed human colorectal explants and primary human intestinal epithelial cells. SIV infection reprogrammed tryptophan (TRP) metabolism, increasing kynurenine catabolite levels that are …

Screening For Relative Energy Deficiency In Sport (Reds) And The Female Athlete Triad In Female Undergraduate Collegiate Athletes: A Quality Improvement Project, Maria A. Marziano

West Chester University Doctoral Projects

This quality improvement (QI) project investigated female collegiate athletes’ knowledge and prevalence of Relative Energy Deficiency in Sport (REDs) and the Female Athlete Triad (Triad). The increase in female athletics brings a growing concern for performance-related health risks, including low energy availability (LEA), menstrual dysfunction, and low bone mineral density (BMD). This study assessed the effectiveness of education and self-screening in identifying at-risk athletes and encouraging resource application for intervention. A mixed-methods design was employed, utilizing retrospective data along with pre- and post-intervention surveys. The study involved 33 female collegiate athletes from lean endurance sports, assessing knowledge, risk factors, and …

Cost-Effective Hierarchical Cobalt Nanostructured Laser-Induced Graphene For Enhanced Uric Acid Detection, Anju Joshi, Gymama Slaughter

Center for Bioelectronics Publications

This study presents an innovative, cost-effective strategy to develop a flexible, enzyme-free biosensor for the sensitive detection of uric acid (UA). Utilizing electrochemically modified cobalt nanostructured on laser-induced graphene electrodes (CoNCs/LIG), this approach surpasses traditional noble metal-based electrocatalysts in sensitivity and affordability. The one-step electrochemical modification method is efficient and straightforward, enabling the uniform deposition of hierarchical flower-like cobalt nanostructures. These structures synergistically enhance the performance of the LIG, resulting in a broad detection range of 5 to 700 µM with a sensitivity of 6.75 µA µM^-¹ cm^-² and a low detection limit of 3.66 µM for UA. …

Sex-Specific Roles Of The Adipocyte Mineralocorticoid Receptor In Obesity And Early Life Stress, Meghan B. Turner

Theses and Dissertations--Pharmacology and Nutritional Sciences

Obesity is a burgeoning health epidemic caused by chronic overnutrition and exacerbated by genetic, environmental and developmental factors. The adipocyte mineralocorticoid receptor (MR), a transcriptionally active nuclear receptor, is speculated to contribute to metabolic dysfunction in the obese state. MR expression is increased in obese adipose tissue, and MR modulates the expression of fat-derived hormones such as leptin and adiponectin. In women, obesity can be exacerbated by early life stress, such as adverse childhood experiences (ACEs). Studies show that women display a positive association between cumulative ACE exposures and increased body mass index. Previously, we demonstrated that maternal separation and …