bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dietary conjugated linoleic acid reshapes high fat diet‐induced microbiota and reduces its immunogenicity
Authors: Leone Vanessa A , Wang Yunwei , Devkota Suzanne , Musch Mark W , Antonopoulos Dionysios , Cook Mark E , Chang Eugene B 
Published: June 2021

The composition of human gut microbiota has shifted over the last century, leading to increased prevalence of autoimmune diseases, such as inflammatory bowel diseases. Shifts in dietary intake to Westernized high fat high carbohydrate diet has influenced this phenomenon. Restoring gut microbiota to a less immunogenic state by altering diet to alleviate gut inflammation is a focus of our research. We hypothesized that supplementing conjugated linoleic acids (CLA), a group of fatty acids with anti‐inflammatory properties, in the presence of high fat diet would result in reshaping the gut microbiota to a less immunogenic state. Mice were fed 18% anhydrous milk fat (AMF) or 18% safflower oil diet with or without CLA for 3 weeks. Microbial 16s rRNA profiles of cecal contents were analyzed via Sanger‐based sequencing. Using wild type spleen‐derived dendritic cells, cecal lysate immunogenicity index was determined by comparing IL‐12p40/IL‐ 10 ratio after culture. Dietary CLA reshaped the enteric microbiota by increasing Firmicutes/Bacteroidetes ratio compared to AMF alone and resulted in decreased δ‐proteobacteria. Lastly, CLA supplementation significantly reduced immunogenicity of cecal lysate. These data suggest dietary CLA supplementation can restore the gut microbiome in the presence of high fat diet and could have positive clinical implications for IBD patients.Grant Funding Source : 5T32DK007074‐38
Fructose, high fructose corn syrup and sucrose solutions: a comparison of their effects on the hypothalamic control of food intake
Authors: Castonguay Thomas W , Colley Danielle 
Published: June 2021

Fructose consumption can influence several systems that regulate food intake in ways that differ from those promoted by glucose intake. In particular fructose access uniquely leads to changes in several genes in the hypothalamus that have been linked to appetite control.Rats were given access to food, water and one of several sugar solutions for 24 h, after which blood and tissues were collected. Separate 16% (w/v) solutions of glucose, sucrose, high fructose corn syrup, and fructose were tested. Despite differences in their sweetness, palatability and metabolic effects, all of the solutions were consumed in similar amounts. All groups given access to sugar consumed more calories than did controls. Overnight fructose access (as opposed to other sugars) led to a doubling of circulating triglycerides. Hypothalamic dopamine receptors 1a and 2 and Neuropeptide Y messages were upregulated in only the fructose fed rats. Hypothalamic Galanin, Brs3, AGRP, INSR, Gh1, Trhr, Atrn, NMB, TNF and Thrb were downregulated only in the fructose group. Unlike fructose, preliminary comparisons of sucrose and HFCS to glucose have failed to reveal any differences in these end points.(Supported by a grant from the Maryland Agricultural Experiment Station)
Prognostic Impact of CD44/CD24 Immunophenotypes on Salivary Gland Malignant Neoplasms
Authors: Soave Danilo Figueiredo , Costa João Paulo Oliveira , Silveira Giorgia Gobbi , Oliveira Lucinei Roberto , Silva Alfredo Ribeiro 
Published: June 2021

SGMN account for 3–6% of head and neck cancers. Cells that express CD44 and CD24 exhibit a stem‐cell‐like behavior. The present study aims to evaluate the influence of CD44 (binding site for hyaluronic acid) and CD24 (P‐selectin receptor) expression on SGMN prognosis and survival outcome. A Immunohistochemical stains for CD44 and CD24 were performed on TMA containing 59 SGMN samples. The CD44, CD24 and CD44/CD24 expression phenotypes were correlated to patient outcome and prognostic factors.The CD44 and CD24 expression correlated with the primary site of injury (PSI) (p=0.006, p=0.05). CD24 was also related with T3/T4 lesions (p=0.027) and clinical stage III/IV (p=0.044). The CD44+/CD24+ profile correlated with the PSI (p=0.0001), locoregional recurrence (p=0.009) and T3/T4 tumors (p=0.017). The cytoplasmic expression of CD24 was related to reduction of disease‐free survival(DFS)(p=0.04). Cox regression revealed that the profiles CD44+/CD24+, CD44+/CD24− and CD44−/CD24− (p=0.003, p=0.001, p=0.003), PSI (p=0.02), clinical stage (p=0.0001), age (p=0.02) and gender (p=0.024) were all independent parameters that predicted DFS. Our data suggest that CD24 expression is associated with reduced DFS and that the CD44+/CD24+ profile represents the more aggressive SGMN.
L‐Glutamine Enhances Wound Healing in Human Colonic Epithelial Cells
Authors: Benton Shana , Hao Li , Merlin Didier , Laroui Hamed , Ziegler Thomas R. 
Published: June 2021

Glutamine (GLN) administration has a variety of cytoprotective effects in intestinal epithelia but little data on GLN in wound healing are available. We studied the effect of L‐GLN on wound healing in human colonic Caco‐2 epithelial cells.MethodsWound injury was induced in Caco‐2 cell monolayers using electric cell substrate impedance sensing (ECIS) technology. At injury, concentrations of L‐GLN ranging from zero to 0.5 mM were added to cell medium ± L‐methionine sulfoximine (MSO), an inhibitor of glutamine synthetase. Continuous resistance (the index of wound healing) and cell permeability measurements were obtained for 38 hrs after cell injury.ResultsIn the absence of MSO, low concentrations of L‐GLN increased Caco‐2 cell resistance/wound healing (0.1mM: P<0.01; 0.3mM: P<0.001; 0.5mM: P<0.001) in a dose‐response manner and decreased cell permeability vs control non‐GLN‐treated cells (P<0.05). In the presence of MSO, only the higher 0.5 mM GLN concentration improved wound healing (P<0.05) and decreased cell permeability compared to control (P<0.05).ConclusionsAfter a standardized wound, L‐GLN improves wound healing and decreases cell permeability in human colonic epithelial cells; exogenous L‐GLN rescues these cytoprotective effects in the absence of endogenous GLN synthesis. Supported by NIH grants K24 RR023356 and T32 DK007298.
Anti inflammatory Peptide F markedly reduces Oxidized Fatty acids in the Brain of LDL Receptor Deficient mouse on a High Fat diet
Authors: Vazirian Samra , Navab Anahita Dona , Vakili Ladan , Safarpour Sheila , Haghnegahdar Maryam , Marvizi Gabriella , Bakhtiari Persia , Swartz Jonathon 
Published: June 2021

IntroductionUpon feeding the LDL receptor deficient mice a high fat diet the circulating apoB containing lipoproteins in the animals rise, lipid oxidation increase and an inflammatory state is induced. Oxidation products of cell membrane arachidonic acid and linoleic acid including HETEs and HODES that are thus produced are known to induce inflammatory molecules in various organs and result in pathological complications.ObjectiveWe sought to study the effect of a high fat diet on the concentration of oxidized fatty acids and the potential protective effect of the anti inflammatory peptide 4F.MethodsGroups of female LDL R−/− mice (n=20 per group) were provided with a high fat‐high cholesterol diet for 6 weeks and were given drinking water or water containing anti inflammatory peptide 4F furnishing 900 ug per animal on a daily basis. At the end of the 56 weeks, using LC‐ESI‐MS/MS brains were analyzed for oxidized fatty acid content.ResultsThe concentration of 5‐HETE, 12‐HETE, 15‐HETE, 9‐HODE and 13‐HODE, PGD2, PGE2, TXB2 were significantly higher in the group that did not receive the peptide as compared to the mice that did receive the peptide 4F (p from 0.039 to 0.002).ConclusionThe oxidative cascade resulted from the hyperlipemia and the inflammatory pressure was inhibited by the anti inflammatory peptide 4F resulting in reduction of the level of proinflammatory oxidized fatty acids and reducing their concentration in brain. If the peptide would have a similar effect in humans, it might have major implications in reducing neuronal inflammation and improvement in CNS function.
Anti‐inflammatory benefits of retinoids: retinoic acid and oxidatively‐transformed β‐carotene induce neutrophil apoptosis and inhibit leukotriene B4 synthesis
Authors: Duquette Stephanie , Fischer Carrie D , Morck Douglas W , Barreda Daniel R , Nickerson James G , Buret Andre G 
Published: June 2021

Clearance of apoptotic neutrophils following infection is critical for the resolution of inflammation. Little is known about the effects of retinoid products (vitamin A derivatives) in innate immune cells in the context of an inflammatory response.HypothesisRetinoic acid (RA) or oxidatively‐transformed β‐carotene (OxβC), a retinoid derivative, may have immuno‐modulatory benefits by promoting neutrophil apoptosis and inhibiting proinflammatory signaling.AimTo evaluate the effects of RA and OxβC in model of Mannheimia haemolytica‐induced bovine respiratory disease, a disease associated with severe inflammation.ResultsIn vitro, RA and OxβC dose‐dependently induced apoptosis, but not necrosis, in circulating bovine neutrophils, but not in epithelial cells. In M. haemolytica‐challenged calves (2×107 CFU), animals that received a 28‐day dietary OxβC treatment (10 mg/kg) had elevated apoptotic leukocytes and reduced LTB4 levels in their lower airways 3 h post‐infection versus infected‐untreated calves.ConclusionRA and OxβC promote cell‐selective apoptosis and inhibit the synthesis of proinflammatory LTB4, which in turn may confer yet unrecognized anti‐inflammatory benefits. Supported by NSERC.
Expression of TLR10 in human lungs and neutrophils
Authors: Balachandran Yadu , Knaus Steven , Singh Baljit 
Published: June 2021

Toll‐like receptors (TLRs) are conserved immune receptors that play critical roles in innate immunity. TLR10 dimerize with TLR1 or TLR2 on the plasma membrane but the identity of its ligand remains unclear. There also is a lack of information regarding expression of TLR10 in the lungs and neutrophils. Because functional TLR10 gene is present in human and chicken but not in mice, we examined TLR10 protein expression in normal and inflamed human and chicken lungs. Immunohistochemistry showed TLR10 in the vascular endothelium in the human and chicken lungs. Immunohistochemistry and Western blots detected an increase in TLR10 protein in lungs of chicken infected with E. coli or Fowl Adenovirus. Human neutrophils stimulated with E. coli lipopolysaccharide (1μg/ml), which binds TLR4, showed increased expression of TLR10 protein at 60 and 120 minutes but a reduction at 90 minutes with Western blots. The surface expression of TLR10 examined with flow cytometry mirrored the changes observed with Western blots. Confocal microscopy showed cytosolic and nuclear TLR 10 in normal neutrophils. TLR10 in activated neutrophils co‐localized with flotallin‐1, a lipid raft marker, and EEA‐1, an early endosomal marker, to suggest its endocytosis. We conclude that TLR10 is expressed in human and chicken lung vasculature, and that LPS alters expression of TLR10 and induce its endocytosis in human neutrophils.Grant Funding Source : NSERC
Inflammatory response is elicited in human cerebrovascular endothelial cells stimulated with blood plasma obtained from Severe Sepsis patients
Authors: Blom Chris James , Fraser Douglas D , Martin Claudio , Patterson Eric K , Cepinskas Gediminas 
Published: June 2021

Mechanisms of sepsis‐associated encephalopathy (SAE) are largely un‐investigated, however, impaired function of cerebrovascular endothelium has been suggested to play a key role. Our recent findings indicate that Severe Sepsis in humans results in up‐regulation of 13 out of 42 pro‐inflammatory cytokines/chemokines analyzed in blood plasma (e.g. IL‐6, MCP‐1, MIP‐1, IL‐8, IP‐10).In this study we used immortalized human‐derived cerebrovascular endothelial cells (hCVEC) to assess activation/dysfunction of hCVEC in response to stimulation with plasma (20% vol/vol) obtained from either patients with Severe Sepsis (hSSP) or healthy controls. Stimulation of hCVEC with hSSP for 1hr resulted in hCVEC activation as evidenced by increased ROS production (DHR123 oxidation). Subsequently, stimulation of hCVEC with hSSP resulted in increased PMN adhesion to hCVEC under conditions of flow (shear stress 1dyn/cm2) and increased hCVEC permeability as assessed by decreased transendothelial electric resistance. Interestingly, hSSP failed to induce activation of inflammation‐relevant transcription factor, NF‐κB (ELISA) following 1hr stimulation.In summary, our data indicate that pro‐inflammatory substance(s) present in human Severe Sepsis plasma induce activation/dysfunction of cerebrovascular endothelial cells, thus may contribute to the development of SAE (IRF 08‐10)
Protective effects of amino acids on the ischemic myocardium via mTOR/S6 kinase pathway
Authors: Tsutsumi Yasuo M , Tanaka Katsuya , Kasai Asuka , Kadota Naoko , Oshita Shuzo 
Published: June 2021

Leucine, as an essential amino acids and activator of mammalian target of rapamycin (mTOR), promotes protein synthesis and suppresses protein catabolism. Recent studies have showed that the mTOR/p70S6K complex may mediate the beneficial effects to ischemia‐reperfusion injury. We therefore proposed that amino acids may produce cardiac protection against myocardial ischemia‐reperfusion mediated by mTOR/p70S6K.Mice were subjected to 30 min of myocardial ischemia followed by 120 min of reperfusion. Control mice were exposed to ischemia and reperfusion only. Some mice were randomly assigned to receive amino acids, administered after ischemia and/or rapamycin, mTOR inhibitor, were given 15 min prior to amino acids postconditioned.Amino acids postconditioned mice were significantly reduced infarct size compared to control group (16 ± 3% vs. 43 ± 4% [n = 6] respectively, p<0.05) and rapamycin eliminated the protection produced by amino acids (45 ± 4% [n = 4]). Additionally, the hearts treated with amino acids had a 2.5‐fold increase in phosphorylation of both mTOR and p70S6K, and pretreated with rapamycin completely abolished mTOR/p70S6K phosphorylations in response to amino acids treatment.These results indicate that amino acids induced myocardial protection involves activation of the p70S6K that is mediated by the mTOR.
Measurement of Contraction‐Induced Blood Flow in Mouse Gastrocnemius Muscle by Optical Imaging of Fluorescent Microspheres
Authors: Valls Aida Freire , Sulaeman Alexis , Wagner Peter D , Breen Ellen C. 
Published: June 2021

In mice, monitoring of blood flow to contracting muscles is technically challenging. We have developed an optical imaging method to measure perfusion using near‐infrared (NIR) fluorescent spheres in gastrocnemius electrically stimulated to contract in situ. It was tested in wild‐type (WT) and muscle‐targeted VEGF gene‐deleted (MckCre x VEGFLoxP) mice.MethodsMice were injected (i.v.) with 200 ul of saline containing 2 μm NIR fluorescent spheres over 2 minutes. The gastrocnemius complex of one leg was stimulated for 3 min. via the sciatic nerve (0.25 pps stim. rate, 6 V). Images were collected simultaneously from stimulated (ES) and resting (REST) gastrocnemius every 5 sec.ResultsMuscle contraction increased the rate of signal accumulation in the ES compared to the REST muscle in all mice. The average ratio of ES/REST fluorescent counts during minute 2 to 3 of the contraction period did not differ between the WT and MckCre mice (2.26 + 0.24 WT, 1.90+ 0.59 MckCre, n=4). There was a trend for signal appearance to be delayed in MckCre mice, an increase above REST occurring at 27 + 21sec post‐stimulation (WT) vs. 148 + 69sec in MckCre mice (p=0.07, n=4).ConclusionOptical imaging of fluorescent NIR microspheres may provide a sensitive and dynamic tool for detecting relative differences in contraction‐induced blood flow to mouse muscle.
A chronic canine model of heart failure and renal insufficiency (cardiorenal syndrome)
Authors: Brewer Robert , Wang Mengjun , Zhang Kefei , Ilsar Itamar , Paone Gaetano , Sabbah Hani N. 
Published: June 2021

IntroductionThe co‐existence of renal insufficiency (RI) in patients with heart failure (HF) often referred to as “cardiorenal syndrome” (CRS), carries an extremely poor prognosis. Understanding the pathophysiology of CRS and development of new therapeutics that address this complex syndrome are hindered by lack of appropriate animal models.ObjectiveWe tested the hypothesis that a unilateral nephrectomy with sustained increase in contralateral renal vein pressure in dogs with established HF would lead to RI with a rise in serum creatinine (sCr) and blood urea nitrogen (BUN) and can serve as a model of CRS.MethodsSix dogs with coronary microembolization‐induced heart failure (LV ejection fraction, EF <30%) were studied. A right nephrectomy was performed in all dogs and the distal left renal vein was banded to increase proximal renal vein pressure from ~10 to ~35 mmHg. sCr and BUN were measured preoperatively, and at 1, 2, 3, 4, 7, and 8 weeks thereafter. A diuretic challenge (DC) was administered (furosemide 80 mg IV) to all dogs 3–4 weeks after surgery. sCr and BUN were measured before and 5 hours after DC.ResultsAll dogs developed RI as evidenced by a significant rise in sCr and BUN that persisted for 8 weeks (Table). DC increased sCr from 1.3±0.1 to 1.6±0.1 mg/dL (p<0.003) and BUN from 24±1.8 to 33±1.8 mg/dL (p<0.001).ConclusionsThe results describe a reproducible canine model of chronic HF and RI (model of CRS) that responds to DC in a manner consistent with the response of CRS patients to IV diuretics.
Acute dietary salt loading impairs cutaneous microvascular function in normotensive salt‐resistant adults: role of oxidative stress
Authors: Greaney Jody L , DuPont Jennifer J , Lennon-Edwards Shannon L , Edwards David G , Farquhar William B 
Published: June 2021

Animal studies have reported dietary salt‐induced reductions in vascular function without an increase in blood pressure (BP). The purpose of this study was to determine if acute dietary salt loading impairs cutaneous microvascular function in normotensive adults with salt‐resistant BP. Following a control run‐in diet, 10 normotensive salt‐resistant subjects (31±3 yr) were randomized to a 7 day high salt (HS; 350 mmol/day) and 7 day low salt (LS; 20 mmol/day) diet (controlled feeding study). Salt‐resistant BP was defined as a change in 24‐hour mean BP of ≤ 5 mmHg from the LS to the HS diet. On the last day of each diet, subjects were instrumented with three microdialysis fibers for the local delivery of Ringer's solution (R), 10 mM L‐NAME, and 20 mM ascorbic acid (AA). Laser Doppler flowmetry was used to measure red blood cell flux during local heating (42□). All data were expressed as a percentage of the maximum cutaneous vascular conductance (CVC) at each site (28 mM SNP; 43□). The plateau %CVCmax was reduced during HS (LS 93±1 v. HS 80±2, P<0.05), as was the nitric oxide (NO) contribution to the plateau (LS 55±5 v. HS 46±3, P=0.075). During HS, AA improved the plateau %CVCmax (R 80±2 v. AA 89±3, P<0.05) and restored the NO contribution (R 46±3 v. AA 60±7, P<0.05). These data suggest that acute dietary salt loading impairs cutaneous microvascular function in normotensive salt‐resistant adults and indicate a role for oxidative stress.Supported by 2 P20 RR016472‐11 and HL104106.
Higher Dietary Niacin Intake is Related to Greater Vascular Endothelial Function Associated with Lower Oxidative Stress Among Healthy Middle‐Aged and Older Adults
Authors: Kaplon Rachelle E , Seals Douglas R , Gano Lindsey B 
Published: June 2021

Endothelium‐dependent dilation (EDD) is impaired with age due in part to decreased activity of the nicotinamide adenine dinucleotide (NAD)‐dependent histone deacetylase sirtuin‐1. We hypothesized that EDD would be related to dietary intake of the NAD precursor niacin among middle‐aged and older (MA/O) adults. In 156 healthy adults aged 45–78, EDD (brachial artery flow‐mediated dilation, FMD) was positively related to self‐reported dietary niacin intake (%Δ: r=0.19, P=0.02). This difference persisted after accounting for clinical characteristics using multiple regression analysis (r=0.16, P=0.04). In a subset of subjects, inhibition of superoxide (infusion of ascorbic acid) improved FMD in niacin insufficient (dietary intake ≤16mg, n=8, 3.7±1.1 vs. 4.7±0.9%, P<0.01), but not sufficient (>16mg, n=19, 5.4±0.5 vs. 5.9±0.6%, P=0.10) adults. Moreover, niacin intake was inversely related to arterial endothelial cell expression of the superoxide‐producing enzyme NADPH oxidase (n=37, r=−0.44, P=0.01). Endothelium‐independent dilation (sublingual nitroglycerin), a measure of vascular smooth muscle sensitivity to nitric oxide, did not differ between groups (P>0.05). These findings suggest that higher dietary niacin intake is associated with greater vascular endothelial function linked to lower oxidative stress among healthy MA/O adults.NIH AG013038, AG006537, AG000279, UL1 RR025780
Polyamine supplementation enhances autophagy and reverses age‐related arterial stiffening
Authors: LaRocca Thomas J , Gioscia-Ryan Rachel A , Fleenor Bradley S , Seals Douglas R 
Published: June 2021

Aging leads to stiffening of large elastic arteries as a result of changes in structural proteins and increased macromolecular damage. Polyamines (PA) play a causal role in survival/longevity and have been reported to induce autophagy, the cellular process of recycling damaged biomolecules. However, the potential for PA to reduce age‐related arterial stiffness is unknown. We studied young (Y: 5 mo, n=7) and old (O: 28–29 mo, n=7) male C57/BL6 mice, and old mice treated with the PA spermidine (OPA: 29 mo, n=7). Aortic pulse wave velocity (aPWV), an index of arterial stiffness, was higher in O vs. Y mice (465 ± 25 vs. 383 ± 21 cm/s, p<0.05). This was associated with ~50% greater aortic levels of both protein carbonyls, an index of oxidative damage, and advanced glycation end products (AGEs), a marker of protein cross‐linking (dot and western blotting, both p<0.05, O vs. Y). PA supplementation (3 mM drinking water × 4w) ameliorated aortic stiffening in old mice (OPA aPWV pre: 482 ± 17 vs. OPA post: 343 ± 14 cm/s, P<0.05) and reversed age‐related increases in protein carbonyls and AGEs. The effects of PA treatment were associated with enhanced autophagy as indicated by an ~20% reduction in acetylation (inhibition) of histone H3, an ~25% increase in expression of the transcription factors AMPK and FOXO3a, and a corresponding increase in LC3‐II and decrease in p62, markers of autophagy and autophagic protein aggregation/damage, respectively (western blotting, all p<0.05, O vs. OPA). These results suggest that PA supplementation may be a novel strategy for reversing age‐related arterial stiffening, perhaps by enhancing autophagic clearance of damaged/aggregated proteins.NIH AG013038, AG039210, HL007822