scholarly journals Impact of Carotenoid Cleaving Enzymes on Lycopene Accumulation in Transgenic Mice

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 69-69
Author(s):  
Joseph Arballo ◽  
Jaime Amengual ◽  
Molly Black ◽  
John Erdman
Keyword(s):  
High Performance ◽  
Statistical Significance ◽  
Control Diet ◽  
Knock Out ◽  
Female Mice ◽  
Funding Sources ◽  
Significance Threshold ◽  
Extrahepatic Tissues ◽  
Total Tissue

Abstract Objectives To evaluate the role of β-carotene oxygenase 1 (BCO1) and BCO2 on lycopene tissue distribution. Methods Three-week old C57BL/6 male and female mice (wild type [WT], Bco1−/−, Bco2−/−, Bco1−/− × Bco2−/− double knock out [DKO]) were divided into groups based on genotype (n = 16 per group split evenly by sex) and fed a powdered AIN 93G control diet for 2 weeks. After this period, mice were gavaged daily for 2 weeks with 1 mg of lycopene dissolved in cottonseed oil. 12 h-fasted mice were then sacrificed, and liver, serum, heart, kidney, intestine, gonadal adipose, prostate, spleen, and testes were harvested. Tissues were preserved in liquid nitrogen and stored at −80 until analyses. We measured lycopene levels in all samples by using high-performance liquid chromatography. Data analyses were performed using two-way ANOVA, followed by the Sidaks test with a statistical significance threshold of P < 0.05. Results Female mice showed higher lycopene levels in the intestine (P < 0.045) and liver (P < 0.007) irrespective of genotype, while male mice had higher lycopene levels in serum (P < 0.004). Intestine, serum, and kidneys exhibited higher lycopene levels in DKO mice compared to all other genotypes (P < .0001), while having higher lycopene levels in testes (P < 0.0001) compared to Bco2−/− and WT mice and adipose (P < 0.005) only in comparison to Bco2−/− mice. DKO exhibited higher lycopene levels in the spleen compared to Bco1−/− mice (P < 0.02). Lycopene levels in the liver (P < 0.0001) were higher in Bco2−/− mice compared to Bco1 −/− and DKO mice, while Bco1−/− mice had lower hepatic lycopene levels compared to all other genotypes. Conclusions Female mice accumulated higher lycopene levels in most tissues compared to males. These results were consistent when data were corrected by total tissue weight. The data suggest the absence of BCO2 favors carotenoid accumulation in many extrahepatic tissues, an effect that is enhanced in the absence of both carotenoid cleaving enzymes. Funding Sources Internal funding, University of Illinois Urbana Champaign.

scholarly journals The Role of Histone Deacetylase 9 in the Therapeutic Effects of Astaxanthin on Non-Alcoholic Steatohepatitis

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1257-1257
Author(s):  
Siqi Hu ◽  
Hyunju Kang ◽  
Hyungryun Jang ◽  
Minkyung Bae ◽  
Mi-Bo Kim ◽  
...  
Keyword(s):  
Histone Deacetylase ◽  
Control Diet ◽  
Genotypic Differences ◽  
Therapeutic Effects ◽  
Inflammatory Genes ◽  
Female Mice ◽  
Hepatic Expression ◽  
Alcoholic Steatohepatitis ◽  
Histone Deacetylase 9

Abstract Objectives The objectives of this study were to determine the role of histone deacetylase 9 (HDAC9) in the development of non-alcoholic steatohepatitis (NASH); and to evaluate the therapeutic effects of astaxanthin (ASTX), a xanthophyll carotenoid, on NASH via the modulation of HDAC9 in vivo. Methods Eight-week-old male and female wild-type (WT) and global Hdac9 knockout (KO) mice (n = 30/sex/genotype) were fed a high-fat/high-sucrose/high-cholesterol (HFHSHC) diet for 20 weeks to induce NASH. Subsequently, subsets of WT (n = 10/sex) and KO (n = 10/sex) mice were sacrificed to examine NASH features and served as baseline controls. The rest of the mice were randomly assigned into two diet groups for another 10 weeks: One continued on the HFHSHC diet, while the other group was fed an HFHSHC containing 0.03% ASTX (w/w). Results After 20 weeks on the HFHSHC diet, male KO mice had lower liver weights and triglycerides than WT, but no genotypic differences were observed in the female. Male KO mice showed less liver steatosis and fibrosis with significant decreases in the hepatic expression of lipogenic genes than male WT mice, but Hdac9 deletion did not inhibit NASH development in female mice. Compared with male KO baseline controls, consumption of control diet for an additional 10 week increased hepatic expression of lipogenic and pro-inflammatory genes in male KO mice, losing the beneficial effect of Hdac9 deletion shown at week 20 on the HFHSHC diet. However, the ASTX diet abrogated the induction. There were no significant differences in hepatic lipid contents and histological features of NASH between any genotypes regardless of ASTX supplementation. Also, additional control diet feeding did not induce any changes in hepatic gene expression in female mice, compared with those on the ASTX diet. Conclusions Hdac9 deletion protected male, but not female, mice from diet-induced hepatic steatosis and fibrosis, which may be attributable to decreased lipogenesis in the liver. However, the protection did not exist when liver damages progressed. Hdac9 deletion or ASTX alone did not alleviate the liver damage progression, but they together inhibited the induction of lipogenic and pro-inflammatory genes in the liver of male mice, indicating that they may have synergistic effects on ameliorating NASH progression. Funding Sources The study was supported by National Institutes of Health.

scholarly journals Untargeted Metabolomic Profiling of Early Diet Energy Intake in C57BL/6 N Mice Reveals Differences Associated with Diet and Aberrant Crypt Foci

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1249-1249
Author(s):  
Haley Chatelaine ◽  
Spencer Kyle ◽  
Cynthia Ramazani ◽  
Susan Olivo-Marston ◽  
Emmanuel Hatzakis ◽  
...  
Keyword(s):  
High Performance ◽  
Linear Models ◽  
High Resolution Mass Spectrometry ◽  
Control Diet ◽  
Aberrant Crypt Foci ◽  
Funding Sources ◽  
Negative Ionization Mode ◽  
Ionization Mode ◽  
Negative Ionization ◽  
Polar Extracts

Abstract Objectives A high-fat (H) diet leads to obesity, a known risk factor for colorectal cancer (CRC). In contrast, calorie restriction (E) is associated with reduced CRC risk. However, the metabolome associated with H vs. E-associated CRC risk has never been directly compared. The different influences of these diets on the proximal (PC), medial (MC), and distal (DC) colon metabolome has also not been studied. Thus, the objective is to elucidate metabolites associated with abberant crypt foci (ACF) number, a marker of CRC risk, in each colon region after consumption of H, E, or a normocaloric control diet (C). Methods 3-week-old C57BL/6 N mice were fed a C, E, or H initiation diet for 13 weeks. In weeks 16–21, animals were injected with azoxymethane to initiate ACF formation, and switched to a C, E, or H progression diet (for a total of 9 diet groups: CC, CH, CE, HH, HC, HE, EE, EC, EH). Polar extracts of the colon regions (i.e., PC, MC, and DC) were analyzed using ultra-high performance liquid chromatography-high resolution mass spectrometry method (HRMS) and 1H NMR metabolomics methods. Linear models assessed the main effects of ACF, initiation diet, progression diet, as well as the diet * ACF interaction, on relative metabolite concentration in each colon region. Results Following HILIC-HRMS analysis of extracts in positive and negative ionization mode, 492 and 415 metabolites were detected, respectively. Linear models revealed 21 metabolites were significantly associated with initiation E diet * ACF (8 unique to MC, 13 unique to PC), 14 with initiation H diet * ACF (only in DC), 27 with progression H diet * ACF (14 unique to DC, 2 to MC, 11 to PC) and 20 with progression E diet * ACF (17 unique to DC, 1 to PC, and 1 common to both). Pathway integration and authentication of tentative metabolite identities with chemical standards is underway. Conclusions Diet * ACF interaction significantly influences multiple metabolite concentrations. Little to no overlap is observed between metabolites associated with ACF in a given colon region and the other regions tested, revealing that the diet * ACF interaction is region-specific. Future studies in humans will determine if these metabolites may serve as early biomarkers for CRC diagnosis. Funding Sources Sample analyses were supported by NIH Award Number Grant P30 CA016058, OSU, and OSUCCC.

Platelet Serotonin in Patients with Analgesic-Induced Headache

Cephalalgia ◽  
1996 ◽  
Vol 16 (6) ◽  
pp. 423-426 ◽  
Author(s):  
A Srikiatkhachorn ◽  
M Anthony
Keyword(s):  
High Performance Liquid Chromatography ◽  
Liquid Chromatography ◽  
Electrochemical Detection ◽  
High Performance ◽  
Statistical Significance ◽  
Platelet Serotonin ◽  
Uptake Mechanisms

The purpose of this study was to investigate the role of serotonin (5HT) in patients with analgesic-induced headache (AIH). We estimated platelet 5HT concentration in patients with AIH, migraine patients and non- headache controls, by using high performance liquid chromatography with electrochemical detection. Our results revealed a significant decrease ( p < 0.00) in platelet 5HT content in patients with AIH as compared to migraine patients and non-headache controls (221.8 ± 30.7, 445.3 ± 37.4 and 467.2 ± 38.5 ng/109 platelets, respectively). In contrast, a difference of lesser statistical significance ( p=0.022) was observed in platelet 5HT content after incubation with excess 5HT (1940.0 ± 195.1, 2610.0 ± 173.1 and 2560 + 165.2 ng/109 platelets for patients with AIH, migraine patients and non-headache controls, respectively). These data suggest that analgesic-induced suppression of 5HT uptake may interfere with the function of the pain modulatory system in the brainstem. Although the process by which analgesics interfere with this system is as vet unknown, it is possible that it may not be entirely due to defective 5HT uptake mechanisms.

scholarly journals OR12-06 Nuclear Receptor CAR Protects Female Mice from the Development of Diet-Induced Nonalcoholic Fatty Liver Disease

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Fabiana Layla Oliviero ◽  
Céline Lukowicz ◽  
Lucile Mary ◽  
Laila Lakhal
Keyword(s):  
Liver Disease ◽  
Hepatic Steatosis ◽  
Nuclear Receptor ◽  
High Fat Diet ◽  
Fatty Liver Disease ◽  
Sexually Dimorphic ◽  
High Fat ◽  
Knock Out ◽  
Female Mice

Abstract NAFLD (Non Alcoholic Fatty Liver Disease) has become the most common cause of chronic liver disease in many developed countries worldwide and represents a major health concern. The prevalence of NAFLD is sexually dimorphic with men suspected to be more susceptible to the development of hepatic steatosis than women. Women are mostly protected until hormonal imbalance induced by menopause. Nuclear receptor CAR (Constitutive Androstan Receptor) is at the crossroads between endocrine and metabolic regulations and could therefore represent an interesting therapeutic target. It is primarily expressed in the liver and involved in the catabolism of hormones such as thyroid hormones, corticosteroids and estrogens. In addition, several studies reveal a metabolic role of CAR through regulation of major hepatic pathways such as neoglucogenesis, beta-oxidation and de novo lipogenesis. Our research is aimed at better understanding the role of CAR using a mouse model genetically deficient for CAR. To explore the metabolic functions of CAR, knock-out male and female mice were subjected to a high fat diet (HFD) for 16 weeks. Concomitant CAR deletion and high fat diet induces sexually dimorphic metabolic disorders. Knock-out of CAR in males exacerbates HFD-induced fasted hyperglycemia whereas in females, it aggravates body weight gain and adipose tissue accumulation. In accordance with epidemiological studies revealing a protection of women from the development of hepatic steatosis, HFD-fed WT female mice present less important hepatic steatosis than HFD-fed WT male mice. However, following CAR deletion, HFD-fed female mice develop a severe steatosis along with important hepatic injury. Ongoing studies aim to understand the transcriptomic and endocrine dysregulations that may explain these phenotypes. These results reveal a previously unrecognized dimorphic role of CAR in energy homeostasis and highlights its involvement in the protection of female mice towards the development of hepatic steatosis. Overall, this research provides further insights in the pathogenesis of NAFLD and its dimorphic prevalence.

Trace nanoanalysis

1994 ◽  
Vol 52 ◽  
pp. 940-941
Author(s):  
D. E. Newbury ◽  
R. D. Leapman
Keyword(s):  
High Performance ◽  
Secondary Ion Mass Spectrometry ◽  
Detection Efficiency ◽  
Volume Element ◽  
And Performance ◽  
Trace Constituents ◽  
Secondary Ion ◽  
Concentration Levels ◽  
Structure Properties

Trace constituents, which can be very loosely defined as those present at concentration levels below 1 percent, often exert influence on structure, properties, and performance far greater than what might be estimated from their proportion alone. Defining the role of trace constituents in the microstructure, or indeed even determining their location, makes great demands on the available array of microanalytical tools. These demands become increasingly more challenging as the dimensions of the volume element to be probed become smaller. For example, a cubic volume element of silicon with an edge dimension of 1 micrometer contains approximately 5×1010 atoms. High performance secondary ion mass spectrometry (SIMS) can be used to measure trace constituents to levels of hundreds of parts per billion from such a volume element (e. g., detection of at least 100 atoms to give 10% reproducibility with an overall detection efficiency of 1%, considering ionization, transmission, and counting).

Two Short Tests Fail to Detect Vigilance Decrements

2001 ◽  
Vol 17 (1) ◽  
pp. 48-55 ◽  
Author(s):  
Juan Botella ◽  
María José Contreras ◽  
Pei-Chun Shih ◽  
Víctor Rubio
Keyword(s):  
Individual Differences ◽  
High Performance ◽  
Selection Process ◽  
Vigilance Task ◽  
Air Traffic Controllers ◽  
Job Selection ◽  
Performance Deterioration ◽  
Short Test ◽  
Psychological Dimensions

Summary: Deterioration in performance associated with decreased ability to sustain attention may be found in long and tedious task sessions. The necessity for assessing a number of psychological dimensions in a single session often demands “short” tests capable of assessing individual differences in abilities such as vigilance and maintenance of high performance levels. In the present paper two tasks were selected as candidates for playing this role, the Abbreviated Vigilance Task (AVT) by Temple, Warm, Dember, LaGrange and Matthews (1996) and the Continuous Attention Test (CAT) by Tiplady (1992) . However, when applied to a sample of 829 candidates in a job-selection process for air-traffic controllers, neither of them showed discriminative capacity. In a second study, an extended version of the CAT was applied to a similar sample of 667 subjects, but also proved incapable of properly detecting individual differences. In short, at least in a selection context such as that studied here, neither of the tasks appeared appropriate for playing the role of a “short” test for discriminating individual differences in performance deterioration in sustained attention.

Effect of human galanin on the response of circulating catecholamines to hypoglycemia in man

1995 ◽  
Vol 133 (6) ◽  
pp. 723-728 ◽  
Author(s):  
Ettore C degli Uberti ◽  
Maria R Ambrosio ◽  
Marta Bondanelli ◽  
Giorgio Transforini ◽  
Alberto Valentini ◽  
...  
Keyword(s):  
Heart Rate ◽  
Healthy Subjects ◽  
Sympathetic Nerve Activity ◽  
Heart Rate Response ◽  
Statistical Significance ◽  
Inhibitory Effect ◽  
Amino Acid Residues ◽  
Nerve Activity ◽  
Receptor Stimulation

degli Uberti EC, Ambrosio MR, Bondanelli M, Trasforini G, Valentini A, Rossi R, Margutti A, Campo M. Effect of human galanin on the response of circulating catecholamines to hypoglycemia in man. Eur J Endocrinol 1995;133:723–8. ISSN 0804–4643 Human galanin (hGAL) is a neuropeptide with 30 amino acid residues that has been found in the peripheral and central nervous system, where it often co-exists with catecholamines. In order to clarify the possible role of hGAL in the regulation of sympathoadrenomedullary function, the effect of a 60 min infusion of hGAL (80 pmol·kg−1 · min−1) on plasma epinephrine and norepinephrine responses to insulin-induced hypoglycemia in nine healthy subjects was investigated. Human GAL administration significantly reduced both the release of basal norepinephrine and the response to insulin-induced hypoglycemia, whereas it attenuated the epinephrine response by 26%, with the hGAL-induced decrease in epinephrine release failing to achieve statistical significance. Human GAL significantly increased the heart rate in resting conditions and clearly exaggerated the heart rate response to insulin-induced hypoglycemia, whereas it had no effect on the blood pressure. We conclude that GAL receptor stimulation exerts an inhibitory effect on basal and insulin-induced hypoglycemia-stimulated release of norepinephrine. These findings provide further evidence that GAL may modulate sympathetic nerve activity in man but that it does not play an important role in the regulation of adrenal medullary function. Ettore C degli Uberti, Chair of Endocrinology, University of Ferrara, Via Savonarola 9, I-44100 Ferrara, Italy

Effects of High Intensity Statin Therapy in the Treatment of Diabetic Dyslipidemia in Patients with Coronary Artery Disease

2018 ◽  
Vol 24 (4) ◽  
pp. 427-441 ◽  
Author(s):  
Marija Vavlukis ◽  
Sasko Kedev
Keyword(s):  
Statin Therapy ◽  
High Intensity ◽  
Statistical Significance ◽  
Incident Diabetes ◽  
Moderate Intensity ◽  
Protective Effects ◽  
Pcsk9 Inhibitors ◽  
Diabetic Dyslipidemia ◽  
Patients With Diabetes

Background: Diabetic dyslipidemia has specifics that differ from dyslipidemia in patients without diabetes, which contributes to accelerated atherosclerosis equally as dysglycemia. The aim of this study was to deduce the interdependence of diabetic dyslipidemia and cardiovascular diseases (CVD), therapeutic strategies and the risk of diabetes development with statin therapy. Method: We conducted a literature review of English articles through PubMed, PubMed Central and Cochrane, on the role of diabetic dyslipidemia in atherosclerosis, the antilipemic treatment with statins, and the role of statin therapy in newly developed diabetes, by using key words: atherosclerosis, diabetes mellitus, diabetic dyslipidemia, CVD, statins, nicotinic acid, fibrates, PCSK9 inhibitors. Results: hyperglycemia and dyslipidemia cannot be treated separately in patients with diabetes. It seems that dyslipidemia plays one of the key roles in the development of atherosclerosis. High levels of TG, decreased levels of HDL-C and increased levels of small dense LDL- C particles in the systemic circulation are the most specific attributes of diabetic dyslipidemia, all of which originate from an inflated flux of free fatty acids occurring due to the preceding resistance to insulin, and exacerbated by elevated levels of inflammatory adipokines. Statins are a fundamental treatment for diabetic dyslipidemia, both for dyslipidemia and for CVD prevention. The use of statin treatment with high intensity is endorsed for all diabetes-and-CVD patients, while a moderate - intensity treatment can be applied to patients with diabetes, having additional risk factors for CVD. Statins alone are thought to possess a small, although of statistical significance, risk of incident diabetes, outweighed by their benefits. Conclusion: As important as hyperglycemia and glycoregulation are in CVD development in patients with diabetes, diabetic dyslipidemia plays an even more important role. Statins remain the cornerstone of antilipemic treatment in diabetic dyslipidemia, and their protective effects in CVD progression overcome the risk of statin- associated incident diabetes.

Do we Need Maintenance Chemotherapy in Advanced NSCLC in the Era of Immune and Targeted Therapy?

2019 ◽  
Vol 15 (1) ◽  
pp. 50-55
Author(s):  
Ahmed Nagy ◽  
Omar Abdel Rahman ◽  
Heba Abdullah ◽  
Ahmed Negida
Keyword(s):  
Lung Cancer ◽  
Maintenance Therapy ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Statistical Significance ◽  
Small Cell ◽  
Maintenance Chemotherapy ◽  
Small Cell Lung ◽  
The Impact

Background: Although well established for the effective management of hematologic cancers, maintenance chemotherapy has only been recently incorportated as a treatment paradigm for advanced non–small-cell lung cancer. Maintenance chemotherapy aims to prolong a clinically favorable response state achieved after finishing induction therapy which is usually predefined in number before startng treatment. There are 2 modalities for maintenance therapy; continuation maintenance (involving a non-platinum component which was a part of the induction protocol or a targeted agent) and switch maintenance therapy (utilizing a new agent which was not a part of the induction regimen). Methods: The purpose of this article is to review the role of maintenance therapy in the treatment of advanced Non-Small Cell Lung Cancer (NSCLC) and provide a brief overview about induction chemotherapy in NSCLC to address the basis of maintenance therapy as a treatment option. We will also compare the impact of maintenance chemotherapy with the now evolving role of immunotherapy in NSCLC. Results: There have been 4 maintenance studies to date showing prolonged PFS and OS with statistical significance. However, Three out of the four studies (ECOG4599, JMEN, and PARAMOUNT) did not report tumor molecular analysis. As regard Immunotherapy, current data is in favour of strongly an increasing role for immunotherapy in NSCLC. Conclusion: Maintenance therapy in NSCLC continues to be an important therapeutic line to improve outcome in patients with metastatic and recurrent disease.

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