scholarly journals A Multi-Mineral Intervention to Modulate Colonic Mucosal Protein Profile: Results from a 90-Day Trial in Human Subjects

Nutrients ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 939
Author(s):  
Muhammad N. Aslam ◽  
Shannon D. McClintock ◽  
Mohamed Ali H. Jawad-Makki ◽  
Karsten Knuver ◽  
Haris M. Ahmad ◽  
...  

The overall goal of this study was to determine whether Aquamin®, a calcium-, magnesium-, trace element-rich, red algae-derived natural product, would alter the expression of proteins involved in growth-regulation and differentiation in colon. Thirty healthy human subjects (at risk for colorectal cancer) were enrolled in a three-arm, 90-day interventional trial. Aquamin® was compared to calcium alone and placebo. Before and after the interventional period, colonic biopsies were obtained. Biopsies were evaluated by immunohistology for expression of Ki67 (proliferation marker) and for CK20 and p21 (differentiation markers). Tandem mass tag-mass spectrometry-based detection was used to assess levels of multiple proteins. As compared to placebo or calcium, Aquamin® reduced the level of Ki67 expression and slightly increased CK20 expression. Increased p21 expression was observed with both calcium and Aquamin®. In proteomic screen, Aquamin® treatment resulted in many more proteins being upregulated (including pro-apoptotic, cytokeratins, cell–cell adhesion molecules, and components of the basement membrane) or downregulated (proliferation and nucleic acid metabolism) than placebo. Calcium alone also altered the expression of many of the same proteins but not to the same extent as Aquamin®. We conclude that daily Aquamin® ingestion alters protein expression profile in the colon that could be beneficial to colonic health.

2021 ◽  
Author(s):  
Muhammad N. Aslam ◽  
Shannon D. McClintock ◽  
Mohamed Ali H. Jawad-Makki ◽  
Karsten Knuver ◽  
Haris M. Ahmad ◽  
...  

ABSTRACTThe overall goal of this study was to determine if Aquamin®, a calcium- and magnesium-rich natural product, would alter the expression of proteins involved in growth-regulation, differentiation and barrier formation in the colon. Thirty healthy human subjects were enrolled in a three-arm, 90-day interventional trial in which Aquamin® (provided daily to deliver 800-mg of calcium per day) was compared to calcium alone and placebo. Before and after the 90-day interventional period, colonic biopsies were obtained. Biopsies were evaluated by immunohistology for expression of Ki67 (a proliferation marker) and for CK20 and p21 (differentiation markers). Tandem mass tag-mass spectrometry-based detection was used to assess levels of multiple proteins. As compared to placebo or calcium, Aquamin® reduced the level of Ki67 expression (20%). Neither intervention altered CK20 expression, while a trend toward increased p21 was observed with calcium and Aquamin® (117% and 99% respectively). In the proteomic screen, Aquamin® treatment resulted in many more proteins being upregulated or downregulated (1.5 fold-change with ≤2% false-discovery rate) than placebo. Included among the upregulated proteins were cytokeratins, cell-cell adhesion molecules and components of the basement membrane. Many of the downregulated proteins were those involved in proliferation and nucleic acid metabolism. Calcium alone also altered the expression of many of the same proteins but not to the same extent as Aquamin®. We conclude that daily Aquamin® ingestion alters protein expression profile in the colon that could be beneficial to colonic health. These data warrant additional studies with a larger sample size to validate these findings.Prevention RelevanceA multi-mineral approach reduced proliferation and induced differentiation in ex vivo settings and has been shown to decrease colon polyp incidence in mouse (polyp-prevention) studies. The findings from a 90-day trial in human subjects (presented here) demonstrated improved biomarker-modulation efficacy, warranting to conduct the polyp-prevention trial in at-risk human subjects.


2014 ◽  
Vol 306 (6) ◽  
pp. F579-F587 ◽  
Author(s):  
Jeff L. Zhang ◽  
Glen Morrell ◽  
Henry Rusinek ◽  
Lizette Warner ◽  
Pierre-Hugues Vivier ◽  
...  

Blood oxygen level-dependent (BOLD) MRI data of kidney, while indicative of tissue oxygenation level (Po2), is in fact influenced by multiple confounding factors, such as R2, perfusion, oxygen permeability, and hematocrit. We aim to explore the feasibility of extracting tissue Po2 from renal BOLD data. A method of two steps was proposed: first, a Monte Carlo simulation to estimate blood oxygen saturation (SHb) from BOLD signals, and second, an oxygen transit model to convert SHb to tissue Po2. The proposed method was calibrated and validated with 20 pigs (12 before and after furosemide injection) in which BOLD-derived tissue Po2 was compared with microprobe-measured values. The method was then applied to nine healthy human subjects (age: 25.7 ± 3.0 yr) in whom BOLD was performed before and after furosemide. For the 12 pigs before furosemide injection, the proposed model estimated renal tissue Po2 with errors of 2.3 ± 5.2 mmHg (5.8 ± 13.4%) in cortex and −0.1 ± 4.5 mmHg (1.7 ± 18.1%) in medulla, compared with microprobe measurements. After injection of furosemide, the estimation errors were 6.9 ± 3.9 mmHg (14.2 ± 8.4%) for cortex and 2.6 ± 4.0 mmHg (7.7 ± 11.5%) for medulla. In the human subjects, BOLD-derived medullary Po2 increased from 16.0 ± 4.9 mmHg (SHb: 31 ± 11%) at baseline to 26.2 ± 3.1 mmHg (SHb: 53 ± 6%) at 5 min after furosemide injection, while cortical Po2 did not change significantly at ∼58 mmHg (SHb: 92 ± 1%). Our proposed method, validated with a porcine model, appears promising for estimating tissue Po2 from renal BOLD MRI data in human subjects.


2010 ◽  
Vol 104 (5) ◽  
pp. 693-700 ◽  
Author(s):  
Robin F. J. Benus ◽  
Tjip S. van der Werf ◽  
Gjalt W. Welling ◽  
Patricia A. Judd ◽  
Moira A. Taylor ◽  
...  

The intestinal microbiota are a complex ecosystem influencing the immunoregulation of the human host, providing protection from colonising pathogens and producing SCFA as the main energy source of colonocytes. Our objective was to investigate the effect of dietary fibre exclusion and supplementation on the intestinal microbiota and SCFA concentrations. Faecal samples were obtained from healthy volunteers before and after two 14 d periods of consuming formulated diets devoid or supplemented with fibre (14 g/l). The faecal microbiota were analysed using fluorescentin situhybridisation and SCFA were measured using GLC. There were large and statistically significant reductions in the numbers of theFaecalibacterium prausnitzii(P ≤ 0·01) andRoseburiaspp. (P ≤ 0·01) groups during both the fibre-free and fibre-supplemented diets. Significant and strong positive correlations between the proportion ofF. prausnitziiand the proportion of butyrate during both baseline normal diets were found (pre-fibre freer0·881,P = 0·001; pre-fibre supplementedr0·844,P = 0·002). A significant correlation was also found between the proportional reduction inF. prausnitziiand the proportional reduction in faecal butyrate during both the fibre-free (r0·806;P = 0·005) and the fibre-supplemented diet (r0·749;P = 0·013). These findings may contribute to the understanding of the association between fibre, microbiota and fermentation in health, during enteral nutrition and in disease states such as Crohn's disease.


1986 ◽  
Vol 60 (4) ◽  
pp. 1321-1326 ◽  
Author(s):  
J. Seltzer ◽  
B. G. Bigby ◽  
M. Stulbarg ◽  
M. J. Holtzman ◽  
J. A. Nadel ◽  
...  

The increase in airway responsiveness induced by O3 exposure in dogs is associated with airway epithelial inflammation, as evidenced by an increase in the number of neutrophils (polymorphonuclear leukocytes) found in epithelial biopsies and in bronchoalveolar lavage fluid. We investigated in 10 healthy, human subjects whether O3-induced hyperresponsiveness was similarly associated with airway inflammation by examining changes in the types of cells recovered in bronchoalveolar lavage fluid obtained after exposure to air or to O3 (0.4 or 0.6 ppm). We also measured the concentrations of cyclooxygenase and lipoxygenase metabolites of arachidonic acid in lavage fluid. We measured airway responsiveness to inhaled methacholine aerosol before and after each exposure and performed bronchoalveolar lavage 3 h later. We found more neutrophils in the lavage fluid from O3-exposed subjects, especially in those in whom O3 exposure produced an increase in airway responsiveness. We also found significant increases in the concentrations of prostaglandins E2, F2 alpha, and thromboxane B2 in lavage fluid from O3-exposed subjects. These results show that in human subjects O3-induced hyperresponsiveness to methacholine is associated with an influx of neutrophils into the airways and with changes in the levels of some cyclooxygenase metabolites of arachidonic acid.


Author(s):  
Nawfal Istfan ◽  
Brook Hasson ◽  
Caroline Apovian ◽  
Tova Meshulam ◽  
Liqun Yu ◽  
...  

A role for fat overfeeding in metabolic dysfunction in humans is commonly implied in the literature. Comparatively less is known about acute carbohydrate overfeeding (COF). We tested the hypothesis that COF predisposes to oxidative stress by channeling electrons away from antioxidants to support energy storage. In a study of 24 healthy human subjects with and without obesity, COF was simulated by oral administration of excess carbohydrates; a 2-step hyperinsulinemic clamp was used to evaluate insulin action. The distribution of electrons between oxidative and reductive pathways was evaluated by the changes in the reduction potentials (Eh) of cytoplasmic (lactate, pyruvate) and mitochondrial (b-hydroxybutyrate, acetoacetate) redox couples. Antioxidant redox was measured by the ratio of reduced to oxidized glutathione. We used cross-correlation analysis to evaluate the relationships between the trajectories of Eh, insulin, glucose, and respiratory exchange during COF. DDIT3 and XBP1s/u mRNA were measured as markers of endoplasmic reticulum stress (ER stress) in adipose tissue before and after COF. Here, we show that acute COF is characterized by net transfer of electrons from mitochondria to cytoplasm. Circulating glutathione is oxidized in a manner that significantly cross-correlates with increasing insulin levels and precedes the decrease in cytoplasmic Eh. This effect is more pronounced in overweight individuals (OW). Markers of ER stress in subcutaneous fat are detectable in OW within 4 hours. We conclude that acute COF contributes to metabolic dysfunction through insulin-dependent pathways that promote electron transfer to the cytoplasm and decrease antioxidant capacity. Characterization of redox during overfeeding is important for understanding the pathophysiology of obesity and type 2 diabetes.


2007 ◽  
Vol 27 (10) ◽  
pp. 1733-1741 ◽  
Author(s):  
Mark Slifstein ◽  
Lawrence S Kegeles ◽  
Robyn Gonzales ◽  
William G Frankle ◽  
Xiaoyan Xu ◽  
...  

The dopamine D1 receptor antagonist radioligand [11C]NNC 112 has previously been reported to have 100-fold selectivity for the D1 receptor compared with the serotonin 5-HT2A receptor. In this study, we tested the selectivity by scanning seven healthy human research volunteers with [11C]NNC 112 before and after 2mg of the antipsychotic drug risperidone, a dose that putatively blocks all 5-HT2A receptors with negligible effect on D1 receptors. We found that specific binding in cortical regions was reduced by 20% to 30%, whereas the striatum showed no change. Based on the known relative densities of these receptors in humans, our results suggest 5- to 10-fold selectivity of [11C]NNC 112 for D1 versus 5-HT2A as opposed to 100-fold selectivity. These results suggest caution in interpreting data from studies using this tracer to measure cortical D1 receptors as well as the need for more selective radioligands to assess cortical D1 receptors.


2002 ◽  
Vol 95 (3) ◽  
pp. 965-972 ◽  
Author(s):  
Fabrice Dosseville ◽  
Sebastien Moussay ◽  
Jacques Larue ◽  
Antoine Gauthier ◽  
Damien Davenne

To identify whether spontaneous motor rhythm is influenced by external or internal events and whether this rhythm fluctuates across the day in parallel with heart rate diurnal variations, we simultaneously recorded heart rate and spontaneous motor rate before and after a pedaling task performed five times a day by 10 healthy human subjects. Each subject performed a Spontaneous Motor Tempo, i.e., a finger-tapping task, at a comfortable and spontaneous cadence. Pre- and postexercise Spontaneous Motor Tempo was measured as well as heart rate. There were diurnal variations in Spontaneous Motor Tempo. Both measures increased significantly after pedaling, suggesting that cardiac and spontaneous rhythms are influenced simultaneously after a moderate exercise. Also, finger-taps occurred most frequently around the initiation of the heart systole. These results suggest that a putative internal clock might regulate Spontaneous Motor Tempo and that cardiac rhythm might influence this tempo


2013 ◽  
Vol 27 (S1) ◽  
Author(s):  
Christian Gerald Krueger ◽  
Jennifer J Meudt ◽  
Amy B Howell ◽  
Christina Khoo ◽  
Dhanansayan Shanmuganayagam

2015 ◽  
Vol 78 (1) ◽  
Author(s):  
Md. Bashir Uddin ◽  
Mohiuddin Ahmad ◽  
Mohd Abdur Rashid

The effects of energy drinks (ED) consumption on electrocardiograph (ECG) and photo plethysmograph (PPG) of several healthy human subjects are evaluated in this study. ECG recordings were performed with electrode lead set connected to MP36 (Biopac, USA) data acquisition unit. PPG recordings were also performed with pulse transducer connected to same data acquisition unit. ECG and PPG recordings were performed before and after having ED available in Bangladesh. Recordings were done with some interval of time from the instant of having ED. After consuming ED, it is observed that the R peak amplitude of ECG which is a vital part of QRS complex increases to a significant value. The maximum increment in R peak amplitude of ECG is found about 4.8% due to having ED which may give a short-term little boost of energy. This increment in R peak amplitude of ECG effectively continues up to 90 to 95 minutes approximately from the instant of being energized. A significant decrement is observed in peak to peak amplitude of PPG and heart rate (HR) due to the consumption of ED which may lead cardiac abnormality as well. Though the consumption of ED gives a short-term energy boost, it may cause any kinds of long- term cardiac diseases.


2021 ◽  
Vol 18 (6) ◽  
pp. 066042
Author(s):  
Bingchuan Liu ◽  
Xinyi Yan ◽  
Xiaogang Chen ◽  
Yijun Wang ◽  
Xiaorong Gao

Abstract Objective. There has become of increasing interest in transcranial alternating current stimulation (tACS) since its inception nearly a decade ago. tACS in modulating brain state is an active area of research and has been demonstrated effective in various neuropsychological and clinical domains. In the visual domain, much effort has been dedicated to brain rhythms and rhythmic stimulation, i.e. tACS. However, less is known about the interplay between the rhythmic stimulation and visual stimulation. Approach. Here, we used steady-state visual evoked potential (SSVEP), induced by flickering driving as a widely used technique for frequency-tagging, to investigate the aftereffect of tACS in healthy human subjects. Seven blocks of 64-channel electroencephalogram were recorded before and after the administration of 20min 10Hz tACS, while subjects performed several blocks of SSVEP tasks. We characterized the physiological properties of tACS aftereffect by comparing and validating the temporal, spatial, spatiotemporal and signal-to-noise ratio (SNR) patterns between and within blocks in real tACS and sham tACS. Main results. Our result revealed that tACS boosted the 10Hz SSVEP significantly. Besides, the aftereffect on SSVEP was mitigated with time and lasted up to 5 min. Significance. Our results demonstrate the feasibility of facilitating the flickering driving by external rhythmic stimulation and open a new possibility to alter the brain state in a direction by noninvasive transcranial brain stimulation.


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