bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adverse Effect of Luteolin on the Anticancer Ability of Oxaliplatin in HCT116 Human Colorectal Carcinoma Cells
Authors: Jang Chan Ho , Moon Nayoung , Oh Jisun , Kim Jong‐Sang 
Published: June 2021

Colorectal cancer (CRC) is one of the most frequently diagnosed cancers in the world. Intracellular oxidative stress by accumulation of reactive oxygen species (ROS) can cause redox imbalance that is associated with higher risks of cancer development. Dietary flavonoids activating a nuclear factor E2‐related factor 2/antioxidant response element (Nrf2/ARE) signaling pathway have received a lot of attention due to their abilities to reduce oxidative stress by expressing antioxidant/phase II detoxifying enzymes. Hence, some cancer patients taking chemotherapeutic agents have been consuming flavonoid‐rich food, expecting their anticancer efficacies to be synergistically enhanced. However, careful consideration of possible undesired effects of flavonoid intake during chemotherapy is needed; flavonoids activating Nrf2/ARE signaling pathway could favor cancer cell survival by attenuating ROS‐induced oxidative stress elevated by anticancer agents. The purpose of the present study was to examine how luteolin would affect chemotherapeutic activity of oxaliplatin, a commonly used anticancer agent for colon cancer, in HCT116 p53+/+ cell line and its derivative HCT116 p53−/− cells. Results showed that luteolin increased ARE‐luciferase activity, decreased ROS level by Nrf2/ARE activation and subsequently stimulated proliferation of oxaliplatin‐treated colorectal cancer cells. In addition, oxaliplatin and a high dose of luteolin induced cell cycle arrest and apoptosis in a p53‐dependent manner, respectively. However, oxaliplatin‐induced cell cycle arrest was compromised by the high dose of luteolin in HCT116 p53+/+ cells. Moreover, the high dose of luteolin suppressed oxaliplatin‐induced p21 expression in HCT116 p53+/+ cells, but not in HCT116 p53−/− cells. Current observations indicate that a high dose of luteolin can negatively affect oxaliplatin‐based chemotherapy in a p53‐dependent fashion, suggesting that Nrf2‐activating flavonoids may interfere with chemotherapeutic efficacy of anticancer agents in colorectal cancer cells that carry functional p53 protein. Further studies about its in vivo impact of luteolin on oxaliplatin‐based chemotherapy are needed to ascertain current findings.Support or Funding InformationThis work was supported by the National Research Foundation of Korea (NRF) grant funded by the Ministry of Science and ICT (MSIT), Republic of Korea.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Protective Effect of Steamed Soybean Wastewater Against Intestinal Inflammation
Authors: Jeong Soojung , Averilla Janice Nullan , Moon Nayoung , Jang Chan Ho , Lim Ji Sun , Oh Ji Sun , Kim Jong‐Sang 
Published: June 2021

Steamed soybean wastewater (SSW) is a commonly produced as a byproduct for manufacturing soybean food such as chonggukjang, doenjang, and natto, and may contain various water‐soluble and biologically beneficial constituents. In this study, we examined the general composition of SSW and additionally the protective effect against colorectal damage caused by dextran sodium sulfate (DSS) in adult male BALB/c mice. The moisture content in the SSW was 90.8±0.42%, crude protein 1.2±0.02%, crude lipid 0.13±0.01%, crude protein 0.85±0.05%, carbohydrate 7.02±0.32%. For animal study, the lyophilized SSW was dissolved in vehicle (consisting of 5% v/v ethanol, 5% v/v tween‐80, and 90% saline) and orally administered at a dose of 1 g/kg body weight on a daily basis for three weeks. Colorectal damage was induced by providing 3.5% (w/v) DSS in drinking water for the last nine days. We found that oral administration of SSW macroscopically and histologically improved DSS‐induced colorectal injury, reduced expressions of inflammatory cytokines and NF‐κB and its downstream proteins in the colorectal tissue, and decreased molecular markers of oxidative DNA damage (assessed by the plasm level of 8‐OHdG) and lipid peroxidation (measured by the MDA level in liver homogenate). These results suggest that dietary SSW can ameliorate colorectal damage by attenuation of inflammatory response.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Impact of Developmental Nicotine Exposure on Cholinergic Airway Signaling
Authors: Rivera Benjamin D , Borrero Nathan G , Cross Seres J.B. , Fregosi Ralph F , Boitano Scott 
Published: June 2021

In 2014, 8.4% of US women reported smoking during pregnancy. Conservatively, this translates into approximately 360,000 smoke‐exposed infants born in 2015 in the United States. Fetal nicotine exposure alters cholinergic signaling through activation of Nicotinic Acetylcholine Receptors (nAChRs) in the developing lung and nervous system. Altered expression of nAChRs can persist and result in lasting changes in lung function. The impact on airway nAChRs, which can influence ion transport to control the airway surface liquid layer and mucociliary clearance, remains poorly defined. Here we begin to discern the impact of an acute nicotine challenge on airway epithelial signaling by evaluating the tracheae of animals exposed to nicotine in utero and after birth (developmental nicotine exposure, DNE) and controls (saline exposed sham). Tracheae were excised from neonate rats between post‐natal days 7 – 12 and were mounted in Ussing Chambers to measure transtracheal resistance (TTR) and short circuit current (Isc) in response to nicotine. The resting TTR in DNE animals trended lower than that in sham‐treated animals. Additionally, it was found that compared to sham, tracheae from DNE‐treated animals displayed significantly larger peak Isc in response to nicotine. Isc experiments of whole neonate tracheae in the presence of epithelial Na+ channel (ENaC), Ca‐induced Cl Channel (CaCC) or CFTR Channel inhibitors (amiloride, DIDS and CFTRinh‐172, respectively) suggest that the bulk of the peak Isc is mediated by CaCC secretion in response to the Ca2+ influx triggered by activation of nAChRs. Preliminary experiments to evaluate changes in nAChR subunit expression between DNE and control animals using mRNA extraction and qPCR suggest altered subunit expression in the DNE‐treated animals. In summary, we report the first Ussing Chamber recordings from rat neonate tracheae and demonstrate significant changes in Isc following DNE. These data highlight the potential physiological changes of early life exposure to nicotine, independent of cigarette smoke.Support or Funding InformationNational Institutes of Health Grants: NIEHS/SBRPP ES094940 (SB), NIEHS/EHS‐TRUE ES025494 (NGB), NICHD HD071302This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Loss of lipoprotein receptor LRP1 ablates neural stem cell migration to ischemic lesions
Authors: Sayre Naomi , Kokovay Erzsebet 
Published: June 2021

Brain damage due to stroke is a leading cause of death and long‐term disability in the US. Treatment options are limited, necessitating a better understanding of reparative and pathological processes after stroke. Ischemia stimulates the proliferation and migration of neural stem cells (NSCs) from the subventricular zone toward the ischemic lesion in mice. During this time, the migrating NSCs differentiate into GFAP positive cells and pro‐reparative glia. While the importance of this process is not fully elucidated, it is clear that limiting NSC response increases lesion size and worsens behavioral outcomes after ischemic stroke. We tested the effect of low‐density lipoprotein receptor related protein 1 (LRP1) on modulating NSC response and differentiation, and found that virtually every aspect of NSC physiology we tested was altered after deletion of LRP1; increased glial differentiation, proliferation, and self‐renewal were measured. After middle cerebral artery occlusion in mice, we observed a marked reduction in the migration of neuroblasts toward the site of the lesion, which correlated with increased gliosis and worsened behavioral outcomes. Loss of LRP1 also caused reduction in expression of the chemokine receptor CXCR4, which could account for the loss of migration. Ongoing studies involve elucidating the mechanism by which LRP1 regulates CXCR4 expression as well as understanding the effect on pro‐reparative processes after stroke.Support or Funding InformationThis research is supported by a pilot grant from the William and Ella Owen's Medical Research Foundation, and a Veteran's Health Administration Career Development Award K2BX003240.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Human Blood Serum Impacts Permeability of the Blood‐Brain Barrier in a Sex‐ and Age‐ Dependent Manner
Authors: Ho Dao H , Gay Elaine A 
Published: June 2021

The blood‐brain barrier (BBB), a semi‐permeable fence between the brain and the blood, maintains homeostatic balance of substances entering and leaving the brain. In the last decade, the causes and consequences of BBB dysfunction have been recognized as the central component of the development and progression of brain‐related illnesses such as Alzheimer's disease (AD), multiple sclerosis (MS), and schizophrenia (SCZ). In these disorders, pathologic BBB leakiness is often caused by changes in the local cellular milieu on the brain‐side as well as on the blood‐side of the BBB. On the brain‐side, injury to neurons, astrocytes, microglia, and pericytes can lead to BBB leakiness, while on the blood‐side, pathophysiologic levels of circulating factors such as hormones, inflammatory cytokines, and immune cells can significantly alter BBB permeability. The goal of this study was to test whether blood serum, which reflects the circulating milieu in the body, can directly alter BBB integrity. We tested the hypothesis that blood serum of patients with secondary progressive multiple sclerosis (SPMS) will increase BBB permeability compared to healthy controls.To test the direct impact of blood serum on BBB integrity, we used three‐dimensional Neurovascular Units (3D NVUs). This in vitro model of the BBB integrates endothelial, neuronal, astrocytic, and microglial cells into a three‐dimensional platform, that allows for the assessment of transendothelial electrical resistance (TEER, Ω cm2). Blood serum of four SPMS patients (two men, two women) and four matched healthy controls (two men, two women) were purchased from PrecisionMed, Inc., and diluted to 40% with cell culture media for testing. TEER was recorded immediately prior to serum exposure (baseline), and again at 24 hours after serum treatment. TEER values were normalized to baseline prior to analysis. The protein levels of 100 different serum cytokines were measured in undiluted serum samples using the Human Cytokine Proteome Profiler (R&D Systems).Stepwise multiple regression analysis revealed that age and sex of the individual were strong predictors of the change in TEER, with serum from female and younger individuals inducing a greater change in TEER (R2=0.81, p=0.01). Presence of SPMS, and levels of cytokines were poor predictors of BBB permeability as measured by TEER. This preliminary study demonstrates that the 3D NVU may be a useful tool in future investigations of the effects of blood serum on BBB integrity.Support or Funding InformationThis project was funded by the TATRC AMEDD Advanced Medical Technology Initiative grant. The views expressed in this abstract are those of the authors and do not reflect the official policy or position of the Department of the Army, Department of Defense, or the U.S. Government.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Hypothalamic C2‐domain protein (C2CD5) involved in protein trafficking and food intake
Authors: Gavini Chaitanya , Cook Tyler , Mansuy‐Aubert Virginie 
Published: June 2021

Rates of overweight and obesity epidemic have risen significantly in the past few decades, and 34% of adults and 15–20% of children and adolescents in the United States are now obese. Melanocortin receptor 4 (MC4R), contributes to appetite control in hypothalamic neurons and is a promising target for anti‐obesity treatments or drug development. While the presence of functional MC4R is crucial for normal neural control of homeostasis and is altered in obesity and in presence of lipids, the mechanisms underlying altered MC4R trafficking are unknown.Our studies identified a novel C2‐domain protein, C2CD5 that appears to contribute to the regulation of MC4R trafficking. We found that 1) the expression of C2CD5 is decreased in diet‐induced obesity models compared to controls, 2) C2CD5 knock‐out mice exhibit pronounced obesity partially due to an increase in food intake compared to control mice when fed a high‐fat diet, 3) C2CD5 colocalize and interacts with MC4R complex, 4) loss of functional C2CD5 alters MC4R endocytosis, and, 5) C2CD5 knock‐out mice exhibit decreased acute responses to Melanotan‐II injection into the paraventricular hypothalamus.Based on these, we hypothesize that hypothalamic C2CD5 is a MC4R trafficking protein that responds to metabolic cues and is involved in neural control of energy balance. These studies provide evidence for a novel pathway and targets, to develop therapeutic drugs potentially to rescue energy balance defects that contribute to the development and maintenance of obesity.Support or Funding InformationThis study was supported by AHA SDG and Loyola University Chicago to VMA.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The Role of Vagal Free Fatty Acid Receptor 3 (FFAR3) in FMT Improvement of Glucose Homeostasis
Authors: Cook Tyler , Bonomo Raiza , Gavini Chaitanya , Gautron Laurent , Layden Brian , Mansuy‐Aubert Virginie 
Published: June 2021

More than 100 million Americans are obese, representing over 35% of the Unites States population. Western diet (WD) is a major cause of the obesity epidemic, and it increases prevalence of many other comorbidities, particularly Type II Diabetes. The western diet consisting of high saturated fat, high cholesterol, high sugar, and heavily processed foods robustly disrupts the composition of the gut bacteria. The microbiome ferments non‐digestible fibers to release short chain fatty acids (SCFA's) which serve as major energy substrates as well as potent signaling molecules through free fatty acid receptors 2 (FFAR2) and 3 (FFAR3). Gut dysbiosis has been associated with changes in SCFA levels that correlate with obesity in humans and mice. The SCFA's propionate and butyrate bind FFAR3 with high affinity, and FFAR3 signaling has been shown to modulate energy expenditure through sympathetic nervous system activation. The role of FFAR3 in the parasympathetic nervous system control of glucose homeostasis is currently unexplored. The vagus nerve primarily consists of sensory afferents which relay specific nutrient information from the periphery to the brain. Several studies have shown that disruption of the vagus nerve eliminates effects of the microbiome and SCFA's altering metabolism, yet the molecular mechanisms of this communication remain largely unknown. We have found that western diet alters SCFA profiles, which have been shown to modulate glucose homoeostasis and energy expenditure in a vagus nerve dependent manner. Furthermore, FFAR3 expression was reduced in the cell bodies of the vagus nerve after WD feeding. We confirmed previous findings that fecal microbiome transplantation (FMT) from lean mice reversed some WD‐induced changes to bacterial composition, plasma SCFA's, and glucose homeostasis. Our data suggest that altered FFAR3 signaling in vagal afferent neurons may contribute to some of the metabolic changes seen upon western diet feeding, and that gut microbes transplanted from lean to obese mice may improve glucose homeostasis through SCFA's binding FFAR3 in the vagus nerve.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Effects of CO2 on Regional Cerebral Blood Flow Regulation During Lower‐Body Negative Pressure
Authors: Thrall Scott F , Green Chantelle , Wynnyk Kristi , Brandt Rachelle , Day Trevor 
Published: June 2021

Cerebrovascular CO2 reactivity (CVR) is differentially regulated between anterior and posterior cerebral circulations, where the cerebrovasculature is responsive to increases (dilation) or decreases (constriction) in arterial CO2. In addition, anterior and posterior cerebral blood flow (CBF) may be differentially regulated during lower body negative pressure (LNBP), where blood volume distribution is experimentally moved toward the lower extremities, imposing an acute hypovolemic and hypotensive challenge. However, the effects of steady‐state increases and decreases in CO2 on the CBF response to LBNP‐imposed hypotension has not been investigated systematically. The aim of this study was to investigate regional CBF responses to incremental (i.e., ramp) LBNP in steady‐state hypo‐ and hypercapnia in anterior and posterior cerebral circulations. We hypothesized that posterior CBF would be better maintained during LBNP at all levels of CO2 and that regional patterns of CBF regulation during LBNP would be unchanged by steady‐state CO2 perturbations. In 14 healthy participants, we measured cardiovascular and cerebrovascular variables, including heart rate (HR; ECG), mean arterial pressure (MAP; finometry), and using transcranial Doppler ultrasound, cerebral blood velocity (CBV) and cerebrovascular conductance (CVC; CBV/MAP) in the middle (MCA) and posterior cerebral artery (PCA). We carried out three separate incremental LBNP protocols (−20, −40, −60 and −80 mm Hg; 3‐min each) at three randomized steady‐state levels of CO2: (a) hypocapnia (−8 mm Hg; i.e., coached hyperventilation), (b) normocapnia (i.e., room air), and (c) hypercapnia (+8 mm Hg; 5% inspired CO2). We found that HR increased incrementally with LBNP in all CO2 conditions (P<0.001). At −80mmHg LBNP, MAP decreased in hypo‐ (P=0.046) and normocapnia (P=0.002). MCA CBV decreased in normo‐ (P<0.001) and hypercapnia (P<0.001). PCA CBV also decreased in normo‐ (P=0.011) and hypercapnia (P=0.002). However, MCA CVC decreased in normo‐ (P=0.01) and hypercapnia (P<0.001), whereas PCA CVC did not decrease during LBNP at all levels of CO2. These findings demonstrate greater sensitivity in anterior cerebral circulation compared to posterior during a moderate LBNP challenge with alterations in CO2. Our data elucidate a comprehensive understanding of regional CVR during LBNP‐induced hypovolemia, and may be applied to understanding preferential protection of posterior brain structures during hypovolemic shock.Support or Funding InformationNSERC Discovery and MRU Faculty of Science and TechnologyThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The Acute Effect of Hyperglycemia on the Exercise Pressor Reflex
Authors: Huo Yu , Grotle Ann‐Katrin , Ybarbo Kai M , Stone Audrey J 
Published: June 2021

Previous work has shown that the exercise pressor reflex is exaggerated in type 2 diabetic rats that present with hyperglycemia. Although it is likely that chronic hyperglycemia plays a role, no studies have isolated the acute effects of high blood glucose levels on this reflex. Therefore, the purpose of the current study was to determine the acute effects of hyperglycemia on the exercise pressor reflex. We first determined the glucose concentration needed to increase local blood glucose level in the hindlimb vasculature to a similar level seen in our type 2 diabetic rats that had an exaggerated exercise pressor reflex. To do this, healthy Sprague‐Dawley rats were infused over 20 min with one of two different concentrations of glucose (125 mg/ml, male n=3 or 250 mg/ml, male n=3) into the arterial supply of the left hindlimb with blood flow to and from the hindlimb restricted. At the same time somatostatin (3.9 ug/100 ul) was infused systemically in order to prevent an endogenous insulin response. Blood glucose was measured every two minutes from both hindlimbs to determine how long it would take to bring blood glucose concentration up to the desired level. We then determined the acute effect of glucose on the pressor and cardioaccelerator responses during static contraction of the hindlimb. The exercise pressor reflex was evoked in healthy, unanesthetized, decerebrated Sprague‐Dawley rats by statically contracting the hindlimb muscle for 30 seconds before and after 15 minutes of either glucose (250 mg/ml) or saline infusion, while mean arterial pressure and heart rate were recorded. We found that infusing 250 mg/ml of glucose significantly raised blood glucose levels to 486 ± 84 mg/dl by the 3rd minute compare to the control leg. However, infusing 125 mg/ml of glucose did not raise blood glucose concentration to 546 ± 33 mg/dl until the 11th minute compare to the control leg (p<0.05). Therefore, we decided to use 250 mg/ml glucose for the exercise pressor experiment. We then found that acutely infusing 250 mg/ml of glucose into the arterial supply of the hindlimb did not significantly affect the pressor (ΔMAP before glucose: 13 ± 0.4 mmHg; after glucose: 12 ± 0.8 mmHg, n=4; before saline: 11 ± 2 mmHg; after saline: 10 ± 2 mmHg, n=3; p>0.05) or cardioaccelerator (ΔHR before glucose: 14 ± 1 bpm; after glucose: 12 ± 2 bpm, n=4; before saline: 14 ± 3 bpm; after saline: 12 ± 4 bpm, n=3; p>0.05) responses to static contraction. We conclude that the acute presence of glucose in the circulation of the hindlimb muscles plays no role in exaggerating the exercise pressor reflex.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.