bluuebunny/crossref_metadata_2025 huggingface dataset:
Enhanced liver regeneration with percutaneous, pulsed, near infrared light: a pilot study
Authors: Russ Tiffany Cherelle , Beeston John , Fisher Robert
Published: June 2021

Purpose

The aim of this study was to determine if photobiomodulation (light therapy), on rats who receive 70% Partial Hepatectomy, enhances both rate and amount of hepatic growth after one week, compared with liver enhancement as a result of Prograf and a control group. Methods and Materials: Twenty‐four male Lewis rats were randomly selected and placed into four groups. Their diet consists of normal rat chow and a 20% glucose solution after surgery. An acclimation period of one week is required pre‐operatively. The left and medial lobes of the liver, 70% in total, will be removed or suture‐ligated. This leaves each animal with only its right and caudate lobes for metabolic function. Group one receives no light and no Prograf (Tacrolimus). The livers of these animals are expected to regenerate naturally. Group two receives one five‐minute treatment of light therapy for five days and no Prograf, group three receives a combination of the two treatments, and group four receives the hepatic stimulus (Tacrolimus).

Results

The results of this experiment are pending due to the need of further investigation. It is still in progress.

Conclusion

If the effects of this light treatment prove to be substantial, then patients who suffer from various liver afflictions and require partial hepatectomy because of these ailments can obtain a faster and less morbid recovery. (Source of Research support: NIDDK)
Visualizing skull in prenatal mice with syndromic craniosynostosis
Authors: DeLeon Valerie Burke , Perlyn Chad A , Prajapati Suresh I , Keller Charles
Published: June 2021

Crouzon syndrome is characterized by premature fusion of multiple cranial sutures and profound facial dysmorphology. Improved treatment requires better understanding of the mechanisms of malformation. This study quantifies the progression of cranial dysmorphology in the Fgfr2+/C342Y mouse model of Crouzon syndrome. Samples of affected and wild‐type littermates were obtained at six developmental time points: E15.5, E17.5, P1, P7, P14, and adult. 3D reconstructions of the skull were created from microCT images using density thresholds. However, as this technique is dependent on the ossification of bone, and dysmorphology may arise earlier in development, we applied a novel method that allows us to visualize developing cranial tissues. Specifically, E15.5 samples were treated with radioopaque stain prior to microCT imaging, and cranial primordia were segmented manually. Morphometric analysis (EDMA) was used to compare shape of affected and wild‐type samples at each time point.

Results indicate that dysmorphology originates in the prenatal period, when significant differences are apparent in the anterior cranial base and, to a lesser extent, the face. Significant brachycephaly becomes evident postnatally. These results confirm that dysmorphology in the mouse model of Crouzon syndrome arises prior to the bony fusion of the sutures, and that the primary defect may be localized to the anterior cranial base.
Differential regulation of adipocyte and osteoblast differentiation of mesenchymal stem cells by Chemerin and CMKLR1
Authors: Shanmugam Muruganandan , Roman Alexandra , Sinal Christopher
Published: June 2021

Adipocytes and osteoblasts are derived from a common mesenchymal stem cell progenitor within the bone marrow. Previous studies have identified an inverse relationship between adipocyte and osteoblast differentiation of these cells in bone marrow. Work from our laboratory identified chemerin as a novel adipokine that together with its cognate receptor, CMKLR1 plays an indispensable role in regulating adipocyte differentiation of 3T3‐L1 preadipocytes. In the present study we hypothesized that chemerin and its cognate receptor, CMKLR1 is also essential for adipocyte differentiation of bone marrow‐derived mesenchymal stem cells and may simultaneously competitively suppress the alternate osteoblastogenic program. Knockdown of chemerin or CMKLR1 by short hairpin loop RNAs (shRNA) in murine bone marrow primary mesenchymal stem cells abrogated preadipocyte clonal expansion, adipogenic gene expression and lipid accumulation along with the promotion of mineralization and osteoblastogenic gene expression. Thus we conclude that chemerin is essential for bone marrow mesenchymal stem cell adipogenesis and may negatively impact osteoblastogenesis in these cells.

Funding:

1. Canadian Institutes of Health Research

2. Nova Scotia Health Research Foundation
Euglena gracilis contains an Ubiquitin‐S27a homologue
Authors: Torres‐Marquez M Eugenia , Diaz‐Mireles Edith
Published: June 2021

Ubiquitination is a widely expressed process in eukaryotic cells. For this postraductional modification to take place, the presence of ubiquitin is necessary. Unicellular organisms, such as the parasite Giardia, have been shown to contain this 8.5kDa polypeptide. However, this ubiquitin finding does not clarify whether the presence of this polypeptide is an adaptation to the host on those organisms or the origin of the posttranslational modifier is related to eukaryotic cell evolution. Thus, the search for a ubiquitin homologue in free living protists, such as Euglena gracilis; becomes relevant as to understand the evolution of signal transduction elements. We were able to find in a E. gracilis cDNA library an Ubiquitin‐S27a protein, which consists of two main domains. The N‐terminal domain is the ubiquitin protein formed by the first 76 amino acids with a molecular weight of 8.5 kDa and a theoretical pI: 6.56. The C‐terminal ribosomal protein S27a is 81 amino acids long with a molecular weight of 9.3 kDa and a pI of 9.88. We are currently scrutinizing in our laboratory whether the ubiquitin‐like protein found in E. gracilis has a role as a protein modifier or as a chaperone at ribosomal assembly.

Partly supported by Grant DGAPA219508
UP‐REGULATION OF MICRO‐RNA‐221 (chr Xp11.3) AND CASPASE‐3 ACCOMPANIES DOWN‐REGULATION OF THE SURVIVIN‐1 HOMOLOGUE BIRC1 (NAIP) IN GLIOBLASTOMA MULTIFORME (GBM)
Authors: Lukiw Walter J. , Li Yuan‐Yuan , Cui Jian‐Guo , Culicchia Frank
Published: June 2021

Glioblastoma multiforme (GBM) represents a class of malignant gliomas which rapidly proliferate, invade and destroy surrounding brain tissues. This study examined micro‐RNA (miRNA) speciation and miRNA effects on gene expression in six ATCC glioma and GBM cell lines and in fourteen glioma and GBM samples obtained from human brain biopsy. We observed selective up‐regulation of miRNA‐221 and down‐regulation of a miRNA‐221 messenger RNA target encoding the survivin‐1 homologue BIRC1, a neuronal inhibitor of apoptosis protein (NIAP) and marker for neurodegeneration. The expression of BIRC5 (survivin‐1) and caspase‐3 were found to be significantly up‐regulated, particularly in stage IV GBM. These studies suggest that the abundance and speciation of the BIRC‐family of neural cell fate regulators are differentially regulated in glioma and GBM, and may contribute to progressive changes in apoptotic signaling and altered neural cell cycling functions.
Design and characterization of a nerve growth factor (NGF) mutein that favors survival over differentiation
Authors: Mehta Hrishikesh , Mahapatra Sidharth , Neet Kenneth E
Published: June 2021

Neurotrophins are required by neurons for differentiation and survival. NGF is involved in survival of the cholinergic neurons of the basal forebrain which are involved in the pathogenesis of Alzheimer's disease. We previously designed a mutein of NGF (F7A, H84A, R103A) which has a lower potential than wtNGF with respect to neuritogenesis in PC12 cells, but supports cell survival. Earlier experiments were performed with unpurified protein from Sf21 insect cell supernatant. We now report the survival and signaling selectivity of purified 7‐84‐103 mutein. NGF initiates signaling through TrkA with downstream signals for differentiation via MAPK phosphorylation and survival via both MAPK and Akt phosphorylation. We compared the phosphorylation of TrkA, MAPK, and Akt with that of wtNGF and another NGF mutein, ▵9/13 that does not bind TrkA. Our data show insignificant differences in the phosphorylation of TrkA and MAPK between buffer and 7‐84‐103 or ▵9/13 (2nM). However, 7‐84‐103 shows significantly higher levels of Akt phosphorylation, about 40% of wtNGF. At 10nM, the 7‐84‐103 mutein shows equivalent levels of phosphorylation of TrkA, MAPK, and Akt compared to 1nM NGF. Thus at moderate concentrations, the 7‐84‐103 NGF mutein supports survival via increased activation of the Akt pathway over the MAPK pathway but, at higher concentrations the mutein signals through both like wtNGF. (Supported by USPHS Grant NS 24380)
Activation of the A2A adenosine receptor modulates the role of kinesin Kif2A in the NGF‐mediated differentiation
Authors: Chern Yijuang , Sun Chung‐Nan , Chuang Hsiu‐Chun
Published: June 2021

The A2A adenosine receptor (A2A‐R) has been implicated in modulating neuronal functions. We previously identified Translin associated protein X (TRAX) as an interacting protein of the A2A‐R. Via a TRAX‐dependent manner, activation of the A2A‐R rescued the NGF‐induced neurite outgrowth impaired by p53 inactivation in PC12. Overexpression of a TRAX‐interacting protein (kinesin Kif2A) also effectively rescued the damaged neurite outgrowth. Down‐regulation of Kif2A using short hairpin RNA (shRNA) further demonstrated its importance. Detailed analyses revealed that expression of Kif2A was elevated in the first 6 hr of NGF treatment, suggesting a critical role of Kif2A in the NGF‐induced differentiation. Blocking the p53‐mediated pathway during NGF‐treatment using p53 mutants or PFT‐ ?Ñ (1) suppressed the NGF‐induced Kif2A expression, (2) prevented the interaction between Kif2A and TRAX, and (3) retained Kif2A in the nucleus. Stimulation of the A2A‐R not only rescued the NGF‐induced neurite outgrowth damaged by p53 blockage, but also translocated Kif2A from the nucleus to the cytosol where the processes of neurite outgrowth occur. Collectively, the above findings suggest that Kif2A is a novel downstream target of p53, and that activation of the A2AR rescued the p53‐impaired neurite outgrowth through a functional interaction between TRAX and Kif2A.
The role of phosphorylation in the regulatory mechanism of the Diaphanous‐related formin, mDia2
Authors: June Cynthia M. , Rawson Jonathan M. , Benson Brittany E. , Albaugh Brittany N. , Veltman Katherine J. , Alberts Arthur S. , Wallar Bradley J.
Published: June 2021

Diaphanous‐related formins (DRFs) are a conserved family of Rho GTPase effector proteins that coordinate the actin and microtubule cytoskeletal networks. This situates the DRFs in a key position to influence cellular shape, motility, and cytokinesis; therefore, it is critical that these proteins are tightly regulated. Normally, DRFs are maintained in an inactive state via intramolecular interactions and can be activated by the binding of Rho GTPases. However, Rho GTPase binding may not be sufficient for mammalian DRF activation. Preliminary experiments by our group have indicated that a second DRF activation signal might be phosphorylation, as we show here that the mouse DRF, mDia2, is phosphorylated by p21‐activated kinase 1 (PAK1). In vitro kinase assays using purified PAK1 and mDia2 mutants have identified serine‐150 as the site of phosphorylation in mDia2. The main activity of PAK1 is to coordinate extracellular signals with the reorganization of the actin cytoskeleton, and mDia2 phosphorylation may be one way this is accomplished. Using an antibody to the phosphorylated serine‐150, we have probed the role of PAK1 phosphorylation in mDia2 regulation in mammalian cells. In addition, our current studies on the cytoskeletal effects of PAK1‐mDia2 regulation, as well as the effects of PAK1 and Rho GTPases on mDia2‐mediated actin nucleation, are providing insight into the mechanism of mDia2 regulation.
Mechanical Strain in VSM Cells Triggers Vascular Remodeling and Hypertension and Activates Integrins in Profilin1 Transgenic Model
Authors: abouelnaga zeinb ahmed , Hassona Mohamed DH , Awad Mohamed M , Alhaj Mazin A , Badary Osama A , Hamada Farid M , Bergese Sergio D , Hassanain Hamdy
Published: June 2021

Remodeling is an adaptive process in response to changes in hemodynamic conditions. Increased actin polymerization in VSMCs induces stress fiber formation playing an important role in vascular remodeling via triggering the hypertrophic signaling pathway. We have overexpressed the cDNA of human profilin 1 in the blood vessels of transgenic mice. Our results showed significant increase in F/G‐actin ratio and in the medial thickness of the profilin1 aortas (P<0.05). Western blotting showed significant increase of Phospho‐ERK1/2 and JNK in profilin 1 VSMCs compared to controls (512.3% and 371.4% respectively, P<0.05). A significant increase in ROCK II kinase and Rho‐GTPase activities in aortas of profilin 1 mice (>400%, P<0.05). Our results confirmed the activation of ?PIX and Rac1 which are downstream of focal adhesion kinase (FAK), and the up‐regulation of á7â1 integrins which could be a negative feedback as a result of vascular hypertrophy and hypertension. Monitoring of blood pressure in profilin1 mice showed significant increase in systolic and mean arterial blood pressure of profilin 1 mice starting at age 6 month (~ 25 mmHg, P<0.05). Isometeric tension analysis in mesenteric arteries showed significant differences in response to vasoactive drugs. Mechanical force is an important modulator of cellular morphology and function and a major contributor to hypertrophy and hypertension.
Vascular Hypertrophy‐Associated Hypertension of Profilin1 Transgenic Mouse Model led to Functional Remodeling of Vasculature
Authors: Hassona Mohamed DH , Abouelnaga Zeinb A , Awad Mohamed M , Alhaj Mazin A , Wani Altaf A , Bergese Sergio D , Hassanain Hamdy
Published: June 2021

Hypertrophy is accompanied with hypertension and till now there is no direct approach to assess the response of these hypertrophic blood vessels towards the vasoactive agents which is important for the treatment of hypertension. We have developed a novel transgenic mouse model by over‐expressing the cDNA of human profilin 1 in the blood vessels of transgenic mice. Our results showed significant increases in F/G‐actin ratio and in the medial thickness of profilin 1 mice (P<0.05). Western blotting confirmed the activation of the hypertrophic signaling in the VSMCs of profilin 1 mice such as Phospho‐ERK1/2 and JNK (512.3% and 371.4% respectively, P<0.05). There was also increase in ROCK II kinase and Rho‐GTPase activities in mesenteric arteries of profilin 1 mice (P<0.05). Our results also showed elevation of blood pressure in profilin1 mice starting at age 6 month (~ 25 mmHg, P<0.05). Functional analyses of mesenteric arteries toward the vasoactive drugs were assessed using wire‐myograph. The results showed significant increase in the vascular responses of profilin1 mesenteric arteries towards phenylephrine, Angiotensin II and Cytochalasin, but, significant decrease in response towards sodium nitrite. In conclusion, vascular hypertrophy of blood vessels led to functional remodeling of the mesenteric arteries as demonstrated by changing the responses towards the vocative agent.
Multisite phosphorylation, cleavage and nuclear translocation of the unstructured PAM cytosolic domain
Authors: Rajagopal Chitra , Francone Victor P , Mains Richard E , Eipper Betty A
Published: June 2021

Neuropeptides are stored in secretory granules to be released at the appropriate time in response to stimulation. Peptidylglycine á‐Amidating Monooxygenase (PAM), a granule membrane protein essential for the biosynthesis of many peptides, has a cytosolic domain (PAM‐CD) that controls its trafficking in both the secretory and endocytic pathways. The aim of this study was to elucidate the role of the unstructured PAM‐CD in signaling via multisite phosphorylation, cleavage and nuclear translocation of a soluble fragment. The 86 amino acids long PAM‐CD has 13 predicted Ser/Thr phosphorylation sites. We identified 6 of these as phosphorylation sites by mass‐spectrometry and phospho‐specific antibody analysis of PAM‐1 in neuroendocrine AtT‐20 cells. Circular dichroism showed that purified recombinant PAM‐CD is unstructured. Two‐dimensional gel electrophoretic analysis of AtT‐20 cell extracts and primary cultures of rat anterior pituitary demonstrated that PAM‐CD can be simultaneously phosphorylated at as many as 10 sites under basal conditions, generating intact protein with pI values between 4.6 and 5.2. We showed that PAM‐CD was cleaved, generating a cytosolic C‐terminal fragment in PAM‐1 AtT‐20 cells, anterior pituitary and atrium. This soluble fragment accumulated in the nucleus, possibly acting as a feedback mechanism to regulate transcription of secretory granule proteins.
Application of human Schwann cells derived from skin neural precursor cells to the engineering of the peripheral nervous system
Authors: Blais Mathieu , Gaudreault‐Morin Saida , Berthod François
Published: June 2021

The isolation of autologous neural precursors from human skin‐derived precursor cells would be a very efficient source of Schwann cells for the treatment of various disorders of the nervous system and also for the development of tissue engineered models to better understand the pathogenesis of neurodegenerative diseases. The purpose of this study was to demonstrate that these neural precursors were able to differentiate into mature Schwann cells and to use them in the engineering of models of the nervous system. We isolated neural precursors from human breast skin and expanded them in vitro. Once cultured in differentiation medium, they have the typical Schwann cells's bipolar morphology. We have shown by indirect immunofluorescent staining and Western Blot that these cells expressed the Schwann cell markers p75NTR, S100B and CNPase. We then reconstructed tissue‐engineered connective tissues enriched with differentiated human Schwann cells. We conclude that the generation of autologous Schwann cells from an accessible adult human source opens many potential therapeutic applications and has a great interest for experimental studies on the normal human Schwann cell physiology.
The role of the MAP kinase transduction pathway in regulating S100B in melanoma
Authors: Gianni Kira , Vitolo Michele I , Shapiro Paul , Weber David J
Published: June 2021

Currently the protein S100B is the strongest prognostic marker available for human melanoma. Increased S100B levels are predictive of disease stage, increased recurrence, and low overall survival. It has previously been found that S100B directly interacts with the tumor suppressor protein p53, down‐regulating its expression, thereby allowing damaged cells to proliferate and mutations to propagate. Establishing the mechanism of regulation for S100B will provide invaluable insight into the protein's role in the progression of melanoma and potentially aid in identifying pharmacological drugs targeting S100B. To advance towards this long‐term goal, we will test the main hypothesis that the elevation of the protein S100B is stimulated by the over‐activity of the MAPK transduction pathway. Of particular interest is the MAPK‐ERK pathway, comprised of RAS‐RAF‐MEK‐ERK, as a substitution mutation (V600E) affecting the RAF isoform BRAF is present in 70% of human melanoma. The V600E mutation renders BRAF constitutively active and results in the sequential phosphorylation and activation of MEK and ERK. Recently, we discovered that suppression of BRAF or MEK in human melanoma cell lines results in decreased ERK phosphorylation and reduced S100B levels. Further experimentation will investigate the role of proteins downstream of ERK as potential direct regulators of S100B.
TRIBUTYLTIN CAUSES ACTIVATION OF C‐RAF IN HUMAN NATURAL KILLER CELLS
Authors: Celada Lindsay J. , Whalen Margaret
Published: June 2021

The toxic chemical Tributyltin (TBT) has been found in human blood. TBT is employed in wood preservation, in marine paints as an antifouling agent, as an antifungal in textiles and industrial water systems, among other things. Human natural killer cells (NK) are a subset of lymphocytes capable of destroying tumor cells, virally infected cells, and antibody‐coated cells. It has been shown that TBT is able to diminish the lytic function of NK cells. Previous studies have demonstrated that exposure to TBT leads to the activation of Mitogen‐Activated‐Protein‐Kinase (MAPK) and MAPK‐Kinase (MAP2K) in NK cells. The focus of this study is to examine whether TBT also results in the activation of MAPK Kinase‐Kinase (MAP3K), c‐Raf, at an exposure time of ten minutes in NK cells. Activation/phosphorylation of c‐Raf (Ser338) was seen with exposure to 300, 200, 100, and 50 nM TBT (2 fold at 300‐100 nM and 1.45 fold at 50 nM). Increased phosphorylation of Ser259 was also seen with 300‐200 nM TBT (2 and 1.7 fold, respectively). Exposures to 300, 200, and 100 nM TBT increased phosphorylation of Ser289/296/301, 2.5, 2.0, and 2.4 fold, respectively. One hour exposures of NK cells to these same concentrations of TBT (300‐ 25 nM) are currently being carried out to see if the effect continues or if it is short‐lived.

Supported by NIH grant S06 GM008092‐33
Analgesic properties of an indigenous polyherbal preparation
Authors: IROANYA ONYEKACHI OGBONNAYA , OKPUZOR JOY ELISABETH , MBAGWU HERBERT , OJOBO PETER DOUGLAS
Published: June 2021

The Pharmacological effect of the polyherbal preparation of an aqueous extract obtained from the leaves of Gongronema latifolia, Vernonia amygdalina and Ocimum gratissimum was evaluated for its analgesic effect and acute toxicity. The effects of the preparation was studied using various in vivo models of analgesic effects (central and peripheral acting analgesics) in mice and the potent inhibitory activity against acetic acid induced mouse writhing , hot plate and formalin induced pain tests.

In control mice, the reaction time to the mouse writhing assay was 91 ± 12.00. The mice injected with 10mg\kg of 0.6% acetic acid (i.p.) presented 68.9% writhes in 15 minutes while treatment with the extract at 2000mg\kg, 4000mg\kg and 8000mg\kg of the extract significantly (P <0.05) and dose dependently reduced the number of writhes by 61.9% , 65.7% and 66.6% writhes respectively in 15 minutes. The extract demonstrated a dose dependent relationship in the hot plate and formalin induced pain assay. The highest dose of the extract presented a significant inhibition 138.5% in comparism to that produced by Morphine 180.8% for the hot plate assay while for the formalin induced pain assay, the highest dose exhibited a significant inhibition of 46% while Acetylsalicylic acid produced a significant inhibition of 49%.

The single oral dose of the Polyherbal extract at 16000mg\kg (p.o.) and 2500mg\kg (i.p.) did not produce mortality or significant change in the general behaviour of the mice.

The data obtained shows that this polyherbal preparation possesses analgesic activity.
The influence of cinnamon supplementation on blood glucose and lipid responses in rats
Authors: Nemoseck Tricia , Clark Christine , Karody Peggy , Skorup Christine , Stocker Kelly , Kern Mark
Published: June 2021

Studies have shown that cinnamon supplementation improves fasting blood glucose levels and lipid profiles in individuals with type 2 diabetes. However, these findings have not been universally reported and limited data are available on the effects of cinnamon on non‐diabetics. The aim of this study was to determine the influence of cinnamon on plasma glucose, cholesterol and triglycerides. Sixteen male weanling Sprague‐Dawley rats were equally divided into two groups and fed either a high‐fat (21g/100g) control diet or a high‐fat diet supplemented with commercial cinnamon (1g/100g) for 30 days. Food intake (420.2 ± 36.0 vs. 457.0 ± 45.1 g), weight gain (189.2 ± 20.9 vs. 189.0 ± 15.1 g), fat pad weights (2.938 ± 0.646 vs. 2.811 ± 0.488 g) and glucose levels (163.0 ± 30.7 vs. 169.8 ± 41.7 mg/dl) were similar (p>0.05) between rats fed cinnamon and the control diet, respectively. Total cholesterol tended to be higher (p=.054) for rats fed cinnamon (93.0 ± 11.6 mg/dl) versus the control diet (80.7 ± 18.8 mg/dl). No differences (p>0.05) in triglyceride (52.8 ± 29.7 vs. 51.3 ± 10.3 mg/dl), HDL‐cholesterol (59.3 ± 8.3 vs. 56.5 ± 5.8 mg/dl) or non‐HDL‐cholesterol (33.8 ± 4.7 vs. 30.13 ± 11.8 mg/dl) levels were detected between the cinnamon‐fed versus control‐fed rats. Cinnamon failed to reduce glucose levels or improve lipids. More research on the proposed health benefits of cinnamon is warranted before generalized claims should be made.
Grain of paradise extracts increase energy expenditure in humans
Authors: Suzuki Isao , Sugishima Yuuki , Sugita Jun , Ikemoto Takeshi , Shimizu Yasutake , Murata Tamami , Akazawa Yumiko , Mori Kenji , Inoue Shintaro
Published: June 2021

Objective

Grain of paradise (GP; Aframomum melegueta) is an herbaceous plant from the ginger family. Two components of GP, paradol and gingerol, are structurally similar to capsaicin, a pungent compound with anti‐obese actions. Our group investigated the effects of GP‐extracts on energy expenditure and the prevention of obesity.

Methods

We investigated the effects of GP‐extracts on norepinephrine (NE)‐induced lipolysis in 3T3‐L1 cells, on the progression of obesity in high fat diet (HFD)‐induced obese mice, and on body weight and energy expenditure in humans receiving repeated doses of the extracts for 4 weeks.

Results

GP‐extracts accelerated lipolysis in 3T3‐L1 cells. In the obese mice, the extracts prevented HFD‐induced elevations in body and adipose tissue weights. In humans, the energy expenditure observed after the intake of GP‐extracts differed significantly from that observed before the intake.

Conclusion

GP‐extracts intake enhances the energy expenditure and basal metabolism in humans, possibly via an acceleration of lipolysis followed by fat combustion. The effects of GP‐extracts on energy expenditure are thought to be caused by paradol and gingerol major components of the extract.
Effects of kale extracts on inflammatory processes in vitro
Authors: Kuntz Sabine , Kunz Clemens , Rudloff Silvia
Published: June 2021

Background

The nutritional impact of vegetables such as kale (Brassica oleraceae) has long been expected to reveal anti‐inflammatory potential. Therefore, we investigated whether water (ws) and fat soluble (fs) extracts of green cabbage affects cytokine induced expression of endothelial cell adhesion molecules as well as the adhesion of leukocytes to endothelial cells (HUVEC).

Methods

HUVEC were incubated with extracts from green cabbage for 24 h and then activated with TNF‐alpha. 5 h later, the expression of ICAM‐1 and VCAM‐1 was determined by RT‐PCR and leukocyte adhesion was measured using a flow model.

Results

The exposure of HUVEC to ws‐ and fs‐ extracts from green cabbage significantly reduced the TNF‐alpha induced expression of cell adhesion molecules. These effects were concentration dependent inhibiting ICAM‐1 expression by 45.5 ± 5.3 % for the ws and 66.8 ± 6.3 % for the fs cabbage extract when compared to controls; VCAM‐1 expression was reduced by 87.5 ± 6.9 % and 76.1 ± 9.4 % for the ws and fs extracts, respectively. At this concentration of cabbage extracts, we also observed a reduced adhesion of leukocytes to HUVEC to about 50 % of the controls.

Conclusion

The inhibitory effect of water and fat soluble ingredients of green cabbage on the expression of cell adhesion molecules in activated endothelial cells as well as on leukocyte adhesion confirmed their anti‐inflammatory potential.
Phytosterols induce changes in hepatic protein expression patterns and increase cholesterol biosynthesis and sterol efflux in a hypercholesterolemic animal model
Authors: Rideout Todd Christopher , Harding Scott V , Jones Peter JH
Published: June 2021

Although phytosterols (PS) modulate intestinal cholesterol metabolism, the role of PS on hepatic sterol trafficking is not known. The objective of this study was to identify hepatic molecular targets responding to oral PS in hamsters (n = 8) fed 0.25% cholesterol diets with or without 2% PS for 28 d. Consumption of PS reduced (P<0.002) plasma total cholesterol (7.8±0.5 vs. 5.3±0.4 mmol/L) vs control. Increased hepatic sterol efflux was suggested by higher LXRβ (P = 0.06, 1.4 fold of control) and ABCG5 (P<0.03, 1.4 fold of control) expression. High sterol fecal output was obersved in PS fed animals. A compensatory increase in fractional absorption of [3, 4]‐13C cholesterol (67.5‰ vs 47.6‰; P<0.02) and 3.7 fold increase (P=0.02) in fractional cholesterol synthesis was also noted in PS animals. Similarly, PS increased (P<0.01) HMGCoA‐R expression to 1.4 fold of control. While PS increased the cytosolic precursor form of SREBP2 (P<0.001) by 3.9 fold, the nuclear active form of SREBP2 was reduced (P<0.005) 2.4 fold relative to control, confirmed in vitro in HepG2 cells treated with PS. This differential regulation might reflect high intracellular levels of both C synthesis intermediates and PS, thereby interfering with normal SREBP2 processing. These data confirm that PS directly affects the expression of hepatic proteins regulating cholesterol trafficking, important for lowering blood cholesterol. Funding: NSERC.
Inhibitiory role of curcumin in adipogenesis
Authors: Kim Choon Young , Kim Kee‐Hong
Published: June 2021

Adipogenesis has been suggested to be a target mechanism to treat and prevent obesity. Induction of inflammatory response and oxidative stress has been observed in the process of adipogenesis. Curcumin having anti‐oxidative and anti‐inflammatory properties brought us to test the hypothesis that curcumin inhibits adipogenesis. We found that curcumin significantly inhibits 3T3‐L1 preadipocyte adipogenesis in vitro in a dose‐dependent manner and a complete inhibition of adipogenesis was observed at 30 µM. Interestingly, curcumin inhibits cell viability of proliferating 3T3‐L1 preadipocytes in a dose‐dependent manner but not in differentiating 3T3‐L1 cells. We also revealed that the inhibitory effect of curcumin on 3T3‐L1 preadipocyte differentiation is limited to the early stage (Day 0 to 2) of adipogenesis. Image analysis of cellular uptake of curcumin revealed the presence of curcumin in the differentiating 3T3‐L1 adipocytes. Furthermore, we found that curcumin significantly reduced mRNA expression levels of adipogenic transcription factors, including peroxisome proliferator‐activated receptorγ (PPARγ) and CAATT/enhancer binding proteinα (C/EBPα), but not C/EBPβ. Taken together, our results support that curcumin has anti‐adipogenic property in vitro and this is likely due to inhibition of mRNA expression of PPARγ and C/EBPα in the early stage of adipogenesis.

Grant Funding Source

Start‐up research fund
Anti‐Inflammatory Effects of Xanthones from Mangosteen in Primary Cultures of Human Adipocytes
Authors: Bumrungpert Akkarach , Kalpravidh R. , Chitchumroonchokchai C. , Chuang C. , West T. , Kennedy A. , McIntosh M.
Published: June 2021

The xanthones, α‐ and γ‐ mangostin (MG), are major bioactive compounds found in mangosteen reported to have anti‐inflammatory activities in several murine models. Given the association between chronic, low grade inflammation and obesity, we examined the anti‐inflammatory effects of α‐ and γ‐ MG in primary cultures of human adipocytes in the presence or absence of lipopolysaccharide (LPS). α‐ and γ‐MG significantly decreased LPS induction of inflammatory adipocytokines (i.e., TNF‐α, IL‐1β, IL‐6, IL‐8, and MCP‐1). Moreover, α‐ and γ‐ MG attenuated LPS activation of the mitogen‐activated protein kinases (MAPK) c‐jun NH2‐terminal kinase (JNK), extracellular signal‐related kinase (ERK), and p38. γ‐ MG was more effective than α‐ MG on an equimolar basis. Furthermore, γ‐MG, but not α‐MG, attenuated LPS‐mediated IκB‐α degradation and nuclear factor‐κB (NF‐κB) transcriptional activity. In conclusion, these data demonstrate for the first time that α‐ and γ‐ MG attenuate LPS‐mediated inflammation in human (pre)adipocytes by inhibiting MAPK or NF‐κB signaling. These data suggest that MG has the potential to attenuate chronic inflammation associated with obesity. (Supported by National Research Council of Thailand)

Grant Funding Source

National Research Council of Thailand
PKCepsilon stimulated arginine methylation of RIP140 for its nuclear‐cytoplasmic export in adipocyte differentiation
Authors: Ho Ping‐Chih , Gupta Pawan , Huq M. D. Mostaqul , Kahn Amjad Ali , Tsai Nien‐Pei , Wei Li‐Na
Published: June 2021

Receptor interacting protein 140 (RIP140) is a transcriptional co‐regulator that plays roles in regulating metabolic processes including fat metabolism in adipocytes. Previously we identified methylation of RIP140 in three arginie residues which promotes RIP140 export to the cytoplasm. Here, we determined the activated PKCepsilon as a trigger for RIP140 arginine methylation by phosphorylating RIP140 at Ser‐102 and Ser‐1003 which synergistically stimulated the formation of RIP140 protein complex, including 14‐3‐3 and protein arginine methyl transferase 1 to methylate RIP140. The methylated RIP140 then preferentially recruited exportin 1 for nuclear export. As a result, the trans‐suppresive activity of RIP140 was reduced. In RIP140 null adipocytes, the defect in fat accumulation was effectively rescued by phosphorylation‐deficient mutant of RIP140 that resided predominantly in the nucleus, but less so by the phosphor‐mimetic RIP140 that was exported to the cytoplasm. This study reveals the role of PKCepsilon in modulating fat metabolism in adipocyte by regulating the cellular distribution of RIP140 through a specific phosphorylation‐arginie methylation mechanism. This work was support by DK54733, DK60521, K02‐DA13926 and DA11190 to L.‐N. Wei.
Dietary Fat Concentration Dependent Trans‐10, Cis‐12 Conjugated Linoleic Acid Induced‐Lipodystrophy: The Role of Adipokines and Hepatic Cholesterol
Authors: Li Edmund , So Martin , Tse Iris
Published: June 2021

The aim of this study was to investigate the interacting effects of dietary fat concentration and trans‐10, cis‐12 conjugated linoleic acid (t10, c12 CLA) on the development of lipodystrophy and mechanisms involved. Male ICR mice received low fat (5 g/100 g, LF) or high fat (30 g/100 g, HF) diets, with or without 0.5 g/100 g t10, c12 CLA (>98% pure) for 27 d. CLA suppressed energy intake (EI) in LF but not HF mice. CLA elevated hepatic cholesterol (CHL) concentration as early as d 13 (P < 0.01) and by d 27 there was a modest increase in triglyceride (P = 0.085). LF/CLA and HF/CLA mice had gradual lost in visceral fat and liver enlargement. The lipodystrophic state occurred in the absence of hyperinsulinemia but was accompanied by reduced leptin, adiponectin and visfatin mRNA in visceral fat; and increased SREBP protein expression, but not FAS expression in liver. Compared to respective control, LF/CLA mice had higher liver CHL concentration than HF/CLA mice. Mice in experiment 2 received the LF diet, LF/CLA diet or were pair‐fed LF diet to the EI of the CLA group (LF/PF). On d 27, LF/CLA mice had ablation of visceral fat and hepatomegaly. The LF/PF mice had significantly higher visceral fat mass and adipokine mRNA but no hepatomegaly. Thus, t10, c12 CLA‐induced lipodystrophy was dietary fat concentration dependent and involved the adipokines. Liver CHL accumulation may reflect an early abnormality in the development of lipodystrophy.
Wild Blueberries (V. angustifolium) Protect Lymphocytes against DNA Damage in Sprague Dawley Rats
Authors: Del Bò Cristian , Riso Patrizia , Ciappellano Salvatore , Martini Daniela , Gardana Claudio , Porrini Marisa , Klimis‐Zacas Dorothy J.
Published: June 2021

The effect of wild blueberry consumption on lymphocyte resistance against oxidative stress was evaluated in Sprague‐Dawley (SD) rats. Sixteen, 5 week‐old SD rats were fed a control (C) or a wild blueberry (WB) diet for 8 weeks. Anthocyanin (ACN) profile in urine and feces was analyzed by LC‐MS/MS. Ex vivo protection from H2O2‐induced DNA damage (500 µmol/L) was evaluated in lymphocytes by the comet assay. No significant differences were detected in body weight between the WB (459 ± 21 g) and C (444 ± 20 g) diet groups or in liver weight (19.4 ± 2.9 g vs. 19.0 ± 1.6 g for WB and C diets respectively). After 8 weeks on the WB diet, ACN concentration in feces and urine was 25.9 ± 9.2 µg/g and 127.6 ± 46.3 ng/ml, while only traces were detected in plasma. No ACNs were found in rats fed the C diet. Metabolites of ACNs (i.e. gallic and hippuric acids) were present in urine and feces of the WB group. Wild blueberry consumption improved lymphocyte protection against oxidative stress. Levels of DNA damage were significantly lower in rats fed the WB diet compared to those on the C diet (11.2 ± 4.1% vs. 17.2 ± 8.0% DNA in tail, p=0.05).We have documented that wild blueberry ACNs are bioavailable in SD rats fed a WB diet for 8 weeks. Additionally, wild blueberry consumption reduced lymphocyte DNA damage from oxidative stress which may have implications on degenerative disease.

This work was supported by a Cariplo Foundation Grant.
Decreased Total Antioxidant Capacity and Increased Oxidative Stress and Serum Ferritin Levels in Untreated Chronic Hepatitis C Patients
Authors: Dichi Isaias , Venturini Danielle , Simão Andrea Colado , Barbosa Décio Sabbatini , Lavado Edson Lopes , Narciso Vitor , Dichi Jane Bandeira
Published: June 2021

The aim of this study was to determine oxidative stress and iron status in untreated patients with chronic hepatitis C (CHC). Two groups (CHC patients and controls) were studied. CHC patients presented significant higher values than the control group in some parameters: serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma glutamyl transferase, iron, ferritin and also in tert‐butyl hydroperoxide initiate chemiluminescence, nitric oxide, thiobarbituric acid‐reactive substances (TBARS) as well as lower values in total radical‐trapping antioxidant parameter. TBARS levels showed a significant correlation with serum AST and ALT levels. TBARS levels were also associated with transferrin saturation. In conclusion, lower antioxidant capacity, higher levels of pro‐oxidants activity and iron liver storage occurs in untreated CHC patients. This greater oxidative activity could play an important role in pathogenesis and evolution of hepatitis C and thus further investigations are needed to define the moment to begin nutritional intervention in CHC patients.
ANTIDIABETIC AND ANTIDYSLIPIDEMIA EFFECTS OF CHUNGKUKJANG AND RED GINSENG‐CHUNGKUKJANG IN MILD HYPERGLYCEMIC SUBJECTS
Authors: Shin Su‐Kyoung , Kwon Joong‐Ho , Jeong Yong‐Jin , Jeon Sun‐Min , Kim Hye‐Jin , Choi Ji‐Young , Do Gyeong‐Min , Choi Myung‐Sook
Published: June 2021

Red ginseng and Chungkukjang are well known as typical Korean functional foods that exhibit various bioactivities. This study was conducted to investigate blood glucose‐lowering activity of chungkukjang and red‐ginseng chungkukjang in hyperglycemic subjects. They were randomly divided into the control (starch, 2g/day), chungkukjang (CH, 20g/day) and red‐ginseng chungkukjang (RGCH, 20g/day) groups. Fasting blood glucose concentration was significantly lowered by 26% in CH group and 18% in RGCH group after 8 weeks compared to the initial value (p<0.001). The levels of blood HbA1c was significantly lowered in the CH group compared to the before supplementation (p<0.05). Total cholesterol and LDL‐cholesterol level were significantly lowered in both the CH (p<0.05) and RGCH (p<0.01) groups than in the control group. FFA level was significantly lowered in experimental groups (p<0.001). Erythrocyte TBARS level was significantly lowered in the CH and RGCH groups compared to respective initial values (p<0.01). It is considered that CH and RGCH are beneficial for regulating fasting blood glucose level and blood lipids level in the mild hyperglycemic subjects.

Grant Funding Source

The second stage of Brain Korea 21
Dietary menhaden oil and resistant starch interact to increase fermentation in large intestine
Authors: Vidrine Kirk , Zhou Jun , McCutcheon Kathleen L , Raggio Anne M , Goita Mfamara , Lammi‐Keefe Carol , Tulley Richard T , Williams Cathleen , Martin Roy J , Keenan Michael J
Published: June 2021

Dietary resistant starch (RS) and fish oil (FO) have been shown independently to reduce body fat in rats. RS may produce this effect through mechanisms and hormone secretions related to colonic fermentation pathways. The objective of this study was to determine additive or synergistic effects when combining Hi‐Maize© RS and Novomega© encapsulated menhaden FO (National Starch). Forty, 5‐week old female rats were free fed for a 4 week weight gain period. Prior to the next feeding period, rats were stratified by weight and placed in 4, energy balanced diet treatment groups: FO, RS, RS/FO, and control. Each group was meal fed for a 2 week restricted feeding period followed by an 8 week free feeding rebound period. Analysis was a 2x2 factorial with significance at p<0.05. The FO showed significantly higher food intake, body weight, and retroperitoneal fat pad weight. Menhaden oil is low in DHA and EPA, which may be necessary for FO to be effective at reducing body fat. RS and RS/FO had larger ceca and lower pH levels in cecal contents indicating increased fermentation. RS/FO had the greatest cecal weight and lowest pH indicating a synergistic interaction between RS and FO which enhanced fermentation to higher levels within the large intestine than RS alone. This combination may benefit the health of the colon. Supported by the LSU AgCenter.
Optimization of γ‐aminobutyric acid production by fermenting with Lactobacillus sp. OPK
Authors: Park Ki‐Bum , Kim Yo‐Han , Oh Suk‐Heung
Published: June 2021

γ‐Aminobutyric acid (GABA) with several well‐known physiological functions is biosynthesized via the irreversible alpha‐decarboxylation of L‐glutamate catalysed by glutamate decarboxylase(GAD). On an industrial scale, the production of GABA from the cheaper mono‐sodium glutamate (MSG) is a valuable process. Lactobacillus sp. strain OPK was isolated from Kimchi, a traditional fermented food in Korea. In this study, we optimized GABA production using the newly isolated and homofermentative lactic acid bacterium, MSG and etc. The optimum pH and temperature for a batch GABA culture of Lactobacillus sp. strain OPK was found to be a 5.5 and 30 centigrade, respectively. The optimum medium mixture was found to be xylose, tryptone, yeast extract and etc. GABA‐generating capacities of Lactobacillus sp. OPK strain were determined by TLC and HPLC method. The results showed that the pH, temperature, carbon and nitrogen source are important factors to have a positive effect on GABA yield. This study provides the optimized conditions for culturing the Lactobacillus sp. OPK, which resulted in the cheapest productivity of GABA.[This work was supported by the Korea Science and Engineering Foundation(KOSEF) grant funded by the Korea government(MEST)(NO.R01‐2008‐000‐20979‐0)]
Moderate energy deprivation increases ubiquitin proteasome activity in physically active adults following endurance exercise
Authors: Carbone John W , Pasiakos Stefan M , Vislocky Lisa M , Anderson Jeffrey M , Giardina Charles , Bruno Richard S , Rodriguez Nancy R
Published: June 2021

The ubiquitin proteasome, the major proteolytic nanomachine in skeletal muscle, is influenced by energy state and endocrine environment. No studies have examined the effect of an acute energy deficit on proteasome activity in humans.

PURPOSE

This study assessed the effect of an acute energy deficit on 26S proteasome activity at rest and following endurance exercise in physically active adults.

METHODS

Men (n=11) and women (n=7) participated in a 20d, two‐phase diet intervention: weight maintenance, WM; and energy deficient, ~80% of energy requirements, ED. Dietary protein (1.5 g·kg−1·d−1) and fat (~30% of total calories) were constant for WM and ED. 26S activity was measured, using a fluorescence‐based assay, following exercise (45min run, 65% VO2peak) and at rest for WM and ED diet interventions. Plasma insulin levels were determined by ELISA.

RESULTS

26S activity increased by 24% (P < 0.05) for ED versus WM post‐exercise. Insulin was lower (P < 0.05) for ED (14 ± 1 μIU/mL) compared to WM (19 ± 2 μIU/mL). The reduction in insulin was inversely correlated to 26S activity (r=0.55, P < 0.01).

CONCLUSIONS

These findings suggest that ubiquitin proteasome activity was upregulated in response to an acute, moderate energy deficit that is potentiated following a bout of endurance exercise. Further research is warranted to investigate the effects of energy homeostasis on the regulation of skeletal muscle proteolysis.
The Effect of Consuming Beans for Four Weeks on Risk Factors for the Metabolic Syndrome
Authors: Luhovyy Bohdan L , Mollard Rebecca C , Panahi Shirin , Anderson Gerald Harvey
Published: June 2021

Regular consumption of beans has been associated with reduced risk of obesity and improved blood lipid profiles. The objective was to determine the effect of consuming 5 cups/week of navy beans on risk factors associated with the metabolic syndrome. Overweight/obese adults (n=16) with BMI of 27‐40 kg/m2 were asked to consume 5 cups per week of canned navy beans for 4 weeks. Blood glucose and insulin were measured over 60 min after a 75g glucose load. A decrease was found in waist circumference (2.5 cm in females and 2.1 cm in males, p<0.05). The effects of beans on pulse rate, TC and LDL were sex dependent. In females, pulse rate increased, while in males pulse rate decreased. In females, TC and LDL did not change. However in males, both TC and LDL decreased (p<0.05). No changes from the beginning to the end of the study were found in body weight, TG, HDL, C‐reactive protein, HbA1, blood pressure and insulin or glucose area under the curve after the glucose load. In conclusion, regular consumption of navy beans has the potential to reduce risk factors associated with the metabolic syndrome. Supported by Ontario Ministry of Agriculture, Food and Rural Affairs, The Ontario Bean Producers, and H. J. Heinz Canada.
Fast food consumption of college students
Authors: Heidal Kimberly B. , Duffrin Melani , Malinauskas Brenda , Al‐Numair Khalid , Buechler Angela
Published: June 2021

Increased fast food consumption has been associated with an increased risk of obesity. Fast food is defined by Webster's dictionary as foods designed for ready availability, use, or consumption and with little consideration given to quality or significance. The purpose of this research was to measure fast food consumption and caloric intake from specific fast food chains located near a college campus. A convenience sample (n=294) of 121 males and 173 females currently enrolled undergraduate college students, ages 18‐22, participated in a survey study that measured dietary intake from seven local fast food chains using a researcher developed food frequency questionnaire. A previously validated college life survey was used to assess lifestyle behaviors. Anthropometrics were taken by trained researchers. The average BMI was 25.75 ± 6.05. The mean frequency of fast food consumption was 12.78 ± 10.77 meals per month. The mean monthly caloric intake from fast food was 13285.67 ± 14584.47 and total dietary fat was 468.75 ± 618.07 g. The small southern town in which this study was conducted was ranked as the number one market for heavy consumption of fast food in a national survey conducted in 2006. The 2006 survey reported similar findings in that the majority of calories were consumed from hamburgers, French fries and soda‐pop.