bluuebunny/crossref_metadata_2025_split huggingface dataset:
Toc isomers modulation of inflammatory response in fhs 74 int fetal‐derived human intestinal cell line
Authors: Elisia Ingrid , Kitts David D. 
Published: June 2021

The effect of α‐Tocopherol (Toc), γ‐Toc and δ‐Toc in modulating inflammatory response of fetal‐derived intestinal cell line (FHs 74 Int) were determined. Toc isomer‐dependently promoted interleukin (IL) 8 expression from FHs 74 Int cells, with δ‐Toc eliciting greatest pro‐inflammatory effect, followed by γ‐Toc and α‐Toc. The IL8 promoting activity was associated with non‐α‐Toc isomers ability to promote NfκB and Nrf‐2 activation as evidenced by the increased nuclear translocation of the transcription factors. Nevertheless, non‐α‐Toc isomers, particularly δ‐Toc, were found to down‐regulate the glutamate cysteine ligase (GCLC) gene expression, an Nrf‐2 target gene that is also the first and rate limiting enzyme involved in glutathione biosynthesis. The possibility that non‐α‐Toc isomers plays role in down‐regulating glutathione biosynthesis was evidenced by the finding that δ‐Toc and to a lesser extent γ‐Toc not only down‐regulated GCLC protein expression but also the total glutathione content of FHs 74 Int cells. Taken together, it is suggested that the down‐regulation of glutathione biosynthesis compromised the cellular defense system that leads to the pro‐inflammatory effect observed for the non‐α‐Toc isomers.Grant Funding Source: Food Nutrition and Health Vitamin Research Fund
Neuroprotective effect of 1′‐acetoxychavicol acetate against amyloid β induced toxicity is related with upregulation of proteasome activity
Authors: Yaku Keisuke , Matsui‐Yuasa Isao , Yuasa‐Kojima Akiko 
Published: June 2021

Introduction1′‐Acetoxychavicol acetate (ACA) naturally obtained from the rhizomes and the seeds of the Zingiberaceae plant such as Languas galangal and Alpinia galangal exhibits anti‐carcinogenesis effect. Though Alpinia galangal has neuroprotective effect in Alzheimer disease induced mice, the effect of ACA on neuroprotection is not clear. Proteasome activity is known to decrease with aging, and the loss of proteasome activity has relation to neurodegenerative process. The present study was conducted to examine the effects of ACA on amyloid β‐protein fragment 25–35 induced neurotoxicity and proteasome activity in PC12.MethodsThe cell number of PC12 was determined by MTT assay. The proteasome activity was measured by using Proteasome‐Glo™ Chymotrypsin‐Like proteasome activity assay kit.ResultsACA recovered the cell number which was decreased by the addition of amyloid β Fragment in PC12. The effect of ACA on amyloid toxicity was decreased by MG132 which is one of the proteasome inhibitors. ACA induced proteasome activity at early stage and remained until at least 9 hours. Then it returned to control level within 24 hours. The structure‐activity relationship of ACA on proteasome activity was different from that on anti‐carcinogenesis.ConclusionACA exhibited neuroprotective effect against amyloid β‐protein fragment 25–35 induced neurotoxicity via upregulation of proteasome activity.
Linking agriculture to nutrition – The harvest is near and how do we measure impact?
Authors: Gannon Bryan M. , Tanumihardjo Sherry A. 
Published: June 2021

An emerging success story in linking agriculture to nutrition is the biofortification of staple crops with micronutrients, namely provitamin A carotenoids, iron, and zinc. As a case study, biofortification of staple crops with provitamin A carotenoids has included sweet potato, maize, and cassava using traditional breeding methods, while transgenic approaches have been utilized in Golden Rice. Human studies have included a variety of technologies, and stable isotope methods are among the most powerful to measure bioavailability and efficacy. Animal and human studies have demonstrated promising β‐carotene to retinol bioconversion factors. Long‐term intake studies in children have been completed or are underway to determine if these favorable bioconversion factors can translate into improved liver reserves of vitamin A. Using the naturally enriched, stable 13C‐signature of maize, the change in 13C‐enrichment in serum retinol was shifted in 3 to 5 year old children eating orange maize for 70 days. This shows that the β‐carotene is bioavailable and contributing to the vitamin A pool. Another study is evaluating changes in total body stores of vitamin A after 90 days of feeding orange maize to 5 to 7 year old children using the 13C2‐retinol isotope dilution test. Effectiveness studies after biofortified maize is broadly introduced are needed to investigate the feeding of β‐carotene enhanced staple crops to population groups. Biofortification of staple crops with provitamin A carotenoids is feasible and all results published to date point towards it being an effective method to improve long‐term vitamin A status of populations that adopt them.Supported by NIH‐5T32DK007665–20 and HarvestPlus
Wolfberry water soluble extracts selectively induce leukemia cell apoptosis
Authors: Ji Hua , Lin Dingbo 
Published: June 2021

ObjectiveOur aim was to determine whether wolfberry water soluble extracts (WWSE) selectively induce apoptosis of leukemia cells, but not normal T‐cells in culture.MethodsContents of taurine, betaine, and rutin of wolfberry water soluble extracts were measured by TLC and/or HPLC. Leukemia Jurkat cells and normal human T cells were treated with WWSE for 48 hours. Cell proliferation, apoptosis, and alteration of gene expression and protein phosphorylation were determined by BrdU assay, flow cytometry, Western blot, and/or immuneprecipitation.ResultsWWSE were enriched in carbohydrates (73.4 ± 4.5 % (w/w)), polyphenolics (1555 ± 112 mg quercetin equivalent/100 g freeze dry powder) including 213 mg rutin/100 g freeze dry powder, betaine (374 ± 25 mg/100 g freeze dry powder), and had enhanced antioxidant activity (7771 ±207 μmol Trolox equivalent/100 g freeze dry powder). WWSE had no effect on growth and proliferation of normal human T cells, but inhibited Jurkat cell proliferation, induced cycle arrest at the G2/M phase in a dose dependent manner starting at 1 mg/mL for 48 h. Furthermore, WWSE down‐regulated SIRT1 protein expression, inactivated cyclin‐dependent kinase 1 (CDK1), and disrupted the interaction of SIRT1 with CDK1 in Jurkat cells only. Knockdown of SIRT1 by specific siRNA caused inactivation of CDK1 leading to Jurkat cell apoptosis.ConclusionsData suggested that consumption of wolfberry could be an efficacious dietary strategy for preventing leukemia. Grant Funding Source: National Institutes of Health COBRE Grant P20‐RR‐017686 and the Kansas State University Cancer Center Research Initiative Award
Vitamin D inhibition of Has2 and hyaluronan synthesis in invasive breast cancer cells
Authors: LaPorta Erika , Welsh JoEllen 
Published: June 2021

1,25‐Dihydroxyvitamin D (1,25D) exerts anti‐cancer actions through the vitamin D receptor (VDR) but the specific targets that mediate these effects remain to be defined. In this study, growth and genomic responses to 1,25D were evaluated in cells derived from mammary tumors generated in VDR knock‐out (KO) and wild‐type (WT) mice. WT145 cells (derived from WT tumors) expressed VDR and were growth inhibited by 1,25D, whereas KO240 cells (derived from VDRKO tumors) lacked VDR and were not growth inhibited by 1,25D. KO240 cell clones stably expressingVDR (KOhVDR cells) were sensitized to 1,25D mediated growth arrest. Genomic profiling of KO240, KOhVDR and WT145 cells identified 35 transcripts that were altered by 1,25D in relation to growth inhibition, with an enrichment of genes involved in heparin sulfate and proteoglycan binding (including Prelp, Hbegf, Fbn1, Postn and Has2). Currently we are focusing on VDR regulation of Has2 in mammary gland and breast cancer. Has2 is the rate‐limiting enzyme in the synthesis of hyaluronic acid (HA) which is strongly associated with tumor invasion and metastasis. To date, we have confirmed down‐regulation of Has2 protein by 1,25D and demonstrated enhanced HA accumulation in mammary gland and tumors of VDRKO mice. These data define a novel role for vitamin D in control of HA synthesis in epithelial tissues that likely contributes to its anti‐cancer actions.NIH R01CA69700
ALOX5 gene variations modulate plasma triglyceride levels during an n‐3 polyunsaturated fatty acid supplementation
Authors: Cormier Hubert , Rudkowska Iwona , Julien Pierre , Couture Patrick , Lemieux Simone , Vohl Marie‐Claude 
Published: June 2021

Single nucleotide polymorphisms (SNPs) in the arachidonate 5‐lipoxygenase (ALOX5) gene may play a role in lowering plasma triglyceride (TG) levels following supplementation with omega‐3 (n‐3) polyunsaturated fatty acids (PUFA).ObjectiveTo examine the effects of n‐3 PUFA supplementation on plasma TG levels in relation to the presence of SNPs in the ALOX5 gene.Methods208 subjects completed a 2‐wk run‐in period followed by a 6‐wk supplementation with 5g/d of fish oil (1.9g of EPA + 1.1g of DHA). Genotyping of 12 SNPs of the ALOX5 gene was performed covering 86% of common genetic variations (minor allele frequency ≥0.05).ResultsGene*diet interaction effects were observed for plasma TG (rs1565096 and rs7913948). Significant differences in TG levels were observed for SNP rs1565096 where AA homozygotes (HMZ) showed a smaller reduction of plasma TG levels as compared to GG HMZ (p=0.04).ConclusionResults suggest that SNPs in the ALOX5 gene may modulate plasma TG levels in response to n‐3 PUFA supplementation. Funding : FAST‐NSERC
Dietary protein diet prevents high fat induced intestinal adaptation and thereby increases intestinal lipid uptake rates in mice
Authors: Schwarz Jessica , Tomé Daniel , Müller Michael R , Hooiveld Guido JEJ 
Published: June 2021

High saturated fat (HF) diets lead to obesity and an associated adaptation in the small intestine (SI), reflected by increased lipid uptake in the middle and distal part. We previously showed that a high protein (HP) diet prevents and reverses obesity and fatty liver even in the context of a HF diet. Our aim was to study if a HP diet can prevent obesogenic adaptation of the SI and consequently affect lipid handling by regional differences in gene expression.Male C57BL/6 mice were fed either a high fat, normal protein (HF‐NP) or a HF‐HP diet for 1 week. After an overnight fast mice received a lipid load containing radio labeled fatty acid (FA) and triglyceride (TG). Appearance of labels in blood was followed over 5 hours. Changes in gene expression in SI were studied using microarray and subsequent gene set enrichment analysis.The HF‐HP diet increased appearance rate of TG (35%, p=0.0407) and FA (29%, p=0.1085) in blood. Transcriptional changes were detected in the metabolism of amino acids along the SI while lipid processing and transport only increased in the proximal part of the SI.Despite a more rapid appearance of lipids in the blood, mice fed the HF‐HP diet do not develop obesity and fatty liver. This suggests that during the HP diet lipids are taken up in the proximal part of the SI and HF diet induced uptake in the lower parts is prevented.This research was supported by a FP7 Marie Curie ERG and by the Dutch Dairy Organisation (NZO).Grant Funding Source: FP7 Marie Curie ERG and by the Dutch Dairy Organisation
High intestinal calcium (Ca) absorption efficiency is positively associated with bone mass in a genetically diverse population of mice
Authors: Replogle Rebecca A , Li Qiang , Fleet James C. 
Published: June 2021

Habitual low Ca intake increases intestinal Ca absorption efficiency (Ca Abs) by a 1,25 dihydroxyvitamin D (1,25D)‐regulated mechanism. We investigated the role of Ca Abs on bone using a diverse population of 11 inbred mouse lines. Mice were fed a normal (0.5%) or low (0.25%) Ca diet from weaning to 3 mo of age and Ca Abs was determined by an oral gavage test. After correcting for the confounding effects of body size; Ca Abs, femur bone mineral density (BMD), trabecular bone volume fraction (BV/TV), and serum 1,25D varied significantly across the 11 lines at baseline and in low Ca adaptive response. Although Ca Abs was correlated to serum 1,25D levels (r=0.35, p<0.05), adaptation of Ca Abs to low Ca intake varied among the lines but was not strongly linked to diet‐induced changes in serum 1,25 D. Despite this heterogeneity, Ca Abs was significantly associated with femur BMD (r=0.17, p<0.05) and BV/TV (r=0.34, p<0.01). Duodenal transient receptor potential vanilloid member 6 and calbindin D9k mRNA levels were significantly correlated to each other (r=0.74), to serum 1,25D (r=0.44 and 0.39, respectively) and to Ca absorption (r=0.42 and 0.43, respectively), supporting the facilitated diffusion model. These results demonstrate the importance of Ca Abs and its adaptation to habitual low Ca intake for protecting bone mass during growth.Grant Funding Source: NIH Award ES19103 to JCF
Chronic administration of low dose EGCG inhibits TNF‐α‐induced IL‐6 and IL‐8 production in rheumatoid arthritis synovial fibroblasts
Authors: Riegsecker Sharayah , Ahmed Salahuddin 
Published: June 2021

Rheumatoid arthritis (RA) is a chronic inflammatory disease in which cytokines stimulate synovial fibroblast proliferation leading to the destruction of the joints. In this study we evaluated the efficacy of chronic low doses of epigallocatechin‐3‐gallate (EGCG), a polyphenol found in green tea, in regulating TNF‐α‐induced IL‐6 and and IL‐8 production. RA snyovial fibroblasts were treated with chronic low doses of EGCG (100–1000 nM) for 7 days followed by TNF‐α stimulation. Conditioned medium was used for the quantification of IL‐6 and IL‐8 by ELISA and cell lysates were prepared for the analysis of signaling proteins. Chronic administration of EGCG inhibited the ability of TNF‐α to induce IL‐6 and IL‐8 production in RA synovial fibroblasts in a dose‐dependent manner(p<0.05). Evaluation of the signaling pathways by Western blotting revealed that chronic exposure of EGCG selectively inhibited TNF‐α‐induced phosphorylation of JNK p54 and AKT, with no or little effect on p‐ERK or p‐P38 MAPKs. These results suggest that the chronic consumption of EGCG, which can be achieved physiologically by drinking green tea, has an ability to decrease the inflammatory millieu and consequently limit joint damage in RA.Grant Funding Source: NIH
The Role of Insulin in Glucose Transporter Expression, Proliferation and Effector Function in Human CD4+ and CD8+ T Cells
Authors: Meng Huicui , Black Adam J , Rogers Connie J 
Published: June 2021

Glucose can be transported into T cells via several glucose transporters. Our preliminary data shows the presence of GLUT‐1, 3 and 4 on human T cells, and significant enhancement in GLUT‐1 and 4 expression upon activation, suggesting increased glucose uptake and metabolism needed for proliferation. T cells are responsive to several hormones, including insulin, which may regulate cell proliferation via its effects on glucose uptake and metabolism in T cells. Insulin can induce GLUT‐4 expression in myocytes and adipocytes, and thus enhance glucose uptake in these cells. However, it is unknown if any of the glucose transporters on T cells are insulin sensitive. The goal of the current study is to determine if insulin can augment T cell activation and effector function via its effect on any of the glucose transporters. Peripheral blood was collected from healthy subjects (20–40 years old), PBMCs were isolated, and T cells were stimulated with anti‐CD3 antibody (1μg/mL) alone, or with insulin (1mU/mL). Following 3‐ day cultures, T cells were harvested, counted and GLUT‐1 and 4 expression was quantified on CD4+ T cells concurrently with CD4+ T cell proliferation. Our current data demonstrates that neither GLUT‐1 and 4 expression nor cell proliferation was altered by insulin in CD4+T cells. Further studies will measure the role of insulin in glucose transporter expression, proliferation and effector function in CD8+ T cells.Grant Funding Source: Penn State Internal Funding
Polymorphisms in Toll‐Like Receptors 2 and 5 Are Associated with Legionella pneumophila infection
Authors: Zhang Fan , Wang Su‐ping , Gao Xiang‐dong , Wu Wei‐wei 
Published: June 2021

Objectivewe investigated whether single nucleotide polymorphisms (SNPs) in Toll‐like receptors2 (TLR2) and TLR5 affect the susceptibility of LD in a Han Chinese population by in vitro assay.MethodFifty four healthy subjects were genotyped for SNPs (TLR2 C597T [rs3804099] and TLR5 C1174T [rs5744168]). Peripheral blood mononuclear cells (PBMCs) were obtained from these subjects and were stimulated with live Legionella pneumophila (Lp) for 24 hours. The mRNA levels were determined using real‐time quantitative Polymerase Chain Reaction (RT‐qPCR) and the levels of TNF‐α, IL‐1β and IL‐6 were measured by enzyme‐linked immunosorbent assay (ELISA).ResultsAfter twenty four hours of Lp stimulation, the mRNA expression level of MyD88 was significantly lower in PBMCs with TLR2(C597T) CT/TT (P=0.0482) or with TLR5(C1174T)CC homozygotes (P=0.0223) comparing to PBMCs with other genotypes. Supernatant from culture of PBMCs with genotype TLR2(C597T) CT/TT or TLR5(C1174T)CC has higher levels of TNF‐α, IL‐1β and IL‐6 comparing to PBMCs with other genotypes after Lp‐stimulation.ConclusionOur findings suggest that both the TLR2(597CT/TT, rs3804099) and the TLR5 (1174CC, rs5744168) polymorphic variants are associated with resistance to LD in the evaluated Han Chinese population.This study was supported by the National Natural Science Funds of China (grant no. 30872154)
Regulation of the Osmotic Tolerance Response in the Halophile Vibrio parahaemolyticus
Authors: Powell Laura Amanda 
Published: June 2021

Vibrio parahaemolyticus is a Gram‐negative, rod‐shaped halophile bacterium present in marine environments worldwide. The bacterium has an absolute requirement for NaCl and can grow in up to 10% NaCl in complex media. Vibrio parahaemolyticus is also a pathogen of humans that causes gastroenteritis usually through the consumption of raw oysters. The V. parahaemolyticus genome contains a large number of compatible solute synthesis and transporter systems that allows it to grow in high NaCl concentrations. How these multiple systems and osmotic tolerance in general are regulated is unknown. In this study, we investigated the regulation of osmotic tolerance by examining the homologue of the EnvZ/OmpR two‐component signal transduction system, vp0155 and vp0154. In Escherichia coli EnvZ/OmpR regulates more than 100 genes, and significantly influences cell growth, metabolism, and motility. For example, in response to osmotic stress the EnvZ/OmpR system has been shown to regulate expression of outer membrane proteins (OMPs). We examine its role in V. parahaemolyticus by deleting a portion of vp0155, an envZ homologue and vp0154, the ompR homologue. Through splicing by overlap extension (SOE) PCR and homologous recombination, a deletion was created in both envZ and ompR. Through homologous recombination and selection, mutants harboring in‐frame deletions in the envZ and ompR genes were created, and confirmed by PCR and sequencing. We describe the effects of our knockout mutations in envZ/ompR in response to NaCl, acid, and alkaline stresses as well as swimming and swarming motility and OMPs and type VI secretion system expression.Research supported by a grant from the Howard Hughes Medical Institute.
Giardia duodenalis genotype A and B are responsible for post infectious visceral hypersensitivity in an immunocompetent suckling rat model: Is commensal bacterial translocation one of the mechanisms leading to PI‐IBS?
Authors: HALLIEZ Marie Christiane , LE GOFF Laetitia , FRANCOIS Arnaud , GARGALA Gilles , FAVENNEC Loic , BURET Andre Gerald 
Published: June 2021

Enteric pathogens such as Giardia duodenalis, common waterborne protozoan parasite, have been linked to Post‐infectious Irritable Bowel Syndrome (PI‐IBS) a functional intestinal disorder, in which visceral hypersensitivity is a key factor. We aimed to develop a model characterizing PI‐IBS triggered by Giardia infection and, reveal mechanisms responsible for the PI‐IBS‐like symptoms, such as the role of the commensal microbiota. Five day‐old Sprague‐Dawley rats gavaged with 104 trophozoites (genotypes A or B) were assessed for visceral hypersensitivity 50 days post‐infection (PI) via jejunal/rectal balloon distension. Changes in blood pressure were recorded as measurements of visceral hypersensitivity. Caco‐2 monolayers were used to assess if Giardia facilitates the translocation of a non‐invasive E. coli at various time points. On day 50 PI, jejunal and rectal hypersensitivity was observed with both genotypes. G. duodenalis also facilitated translocation of non‐invasive E. coli through Caco‐2 monolayers 3h PI. Hypersensitivity was detected in the jejunum, as well as in the rectum, a site beyond the infection area, indicating that the effect is not limited to the presence of the pathogen. Giardia facilitates the passage of non‐invasive bacteria through the intestinal epithelium, mechanism which could cause PI‐IBS. This study describe a new model for the study of protozoa‐induced PI‐IBS.fundings: NSERC Create, FFCR (France‐Canada Research Fund), CCFC
Atorvastatin‐induced cardiac function impairment
Authors: Qiao Congzhen , Lauver Dale Adam , Lucchesi Benedict 
Published: June 2021

Statins, known as 3‐hydroxy‐3‐methylglutaryl coenzyme A (HMG‐CoA) reductase inhibitors, are reported to reduce low‐density lipoprotein cholesterol levels in blood. In spite of the dramatic cholesterol‐lowering effect, statin‐induced myalgia and fatigue have been widely reported. The inhibition of HMG‐CoA reductase by statins prevents the synthesis of mevalonate, a precursor for the synthesis of cholesterol as well as coenzyme Q10 (CoQ10). It has been well documented that CoQ10 plays a critical role in the synthesis of mitochondrial adenosine‐5′‐triphosphate (ATP), the depletion of which can cause a reduction of intracellular ATP, leading to myalgia. Given the high‐energy demand that cardiac muscle requires, we are interested in statin's off‐target effect on the skeletal and cardiac muscle in rabbits. Several clinical studies have shown that there is a link between the reduction of CoQ10 and cardiomyopathy. In addition, endomyocardial biopsies have shown a decrease of myocardial ATP in a failing heart, suggesting that the reduction of ATP may exacerbate heart failure and contribute to heart remodeling. However, few publications have reported the adverse cardiac effects of statins most likely due to the depletion of ATP. To address this issue, we demonstrated atorvastatin's effect on rabbit cardiac function by employing Langendorff heart model as well as morphological changes detected by transmission electronic microscopy. Our preliminary data suggest that atorvastatin impairs cardiac function in 7 and 28 days treatment compared to placebos. In addition, the disruption of the mitochondrial ultrastructure in 28 days atorvastatin‐treated group indicates a long‐term deleterious cardiac effect of atorvastatin. Hence, we believe that statin‐induced CoQ10 deficiency leads to the depletion of ATP, which impairs heart function and may contributes to the pathogenesis of heart failure.The source of research support: the University of Michigan Cardiovascular Research Fund