bluuebunny/crossref_metadata_2025_split huggingface dataset:
Usefulness of dietary flaxseed in abrogating lung damage associated with space exploration: antioxidant and anti‐inflammatory effects of flaxseed in a murine model of repeated double‐hit low‐level radiation and hyperoxia exposure
Authors: Pietrofesa Ralph A , Dukes Floyd , Tyagi Sonia , Arguiri Evguenia , Solomides Charalambos C , Christofidou-Solomidou Melpo 
Published: June 2021

Crew members during spaceflight missions must conduct extra‐vehicular activities (EVA) which may expose them to lung damaging hyperoxia and low levels cosmic/galactic radiation. Flaxseed (FS) has lung protective properties in mouse models of acute and chronic lung injury. To test the usefulness of FS as a dietary supplement for such missions, we evaluated FS in a murine model of double‐hit hyperoxia and radiation. Mouse cohorts (n=5/group) were pre‐fed diets containing either 0% FS or 10% FS for 3 wks and exposed to: a) normoxia; b) >95% O2 (O2); c) 0.25Gy gamma radiation (RAD); or d) a combination of O2 and RAD (O2+RAD). Challenge (O2 or RAD) was given 3X weekly for 2 wks; 8‐hour hyperoxia was spanned by normoxic intervals. Lungs were evaluated for oxidative damage, inflammation, injury and fibrosis. 0% FS‐fed mice developed significant lung injury and inflammation across all challenges, as evidenced by bronchoalveolar lavage (BAL) neutrophils (p<0.003), BAL protein levels and increased oxidative tissue damage (p<0.008). Lung hydroxyproline content increased in 0% FS‐fed mice exposed to RAD and O2+RAD (p<0.001). All adverse effects due to challenge conditions were ameliorated in FS‐fed mice. In conclusion, dietary FS is protective in a murine model of repeated low‐level radiation and hyperoxia exposure. Funded by: NIH/NCI, NASA (MCS)Grant Funding Source: NIH/NCI/NASA
Anti‐oxidant and Anti‐inflammatory Activity of Tocopherol Isomers Modulates the Nrf‐2 and NfκB Activation in Caco‐2 Human Intestinal Cell Line
Authors: elisia ingrid , Kitts David 
Published: June 2021

The objective of this study was to determine if the antioxidant activity of tocopherol (Toc) isomers translated to a protection against inflammation through oxidative‐stress related pathways in the Caco‐2 intestinal cell line. Antioxidant activities of major Toc isomers, determined using Oxygen Radical Absorbance Capacity (ORAC) chemical assay, followed a relative order of δToc>γToc>αToc. The anti‐inflammatory activity of Toc isomers was determined using interferon γ/phorbol myristate acetate (IFNγ/PMA) cocktail to stimulate interleukin 8 (IL8) secretion from Caco‐2 cells. Both αToc and γToc concentration‐dependently suppressed IL8 production from IFNγ/PMA‐stimulated cells. Delta Toc on the other hand was more effective at a lower concentration to modulate IL8 production compared to αToc and γToc, while being the least effective high concentration. Exposure of Caco‐2 cells to IFNγ/PMA activated both stress‐responsive NfκB pro‐inflammatory and Nrf2 antioxidant enzyme pathways. Only αToc concentration‐dependently suppressed NfκB activation induced by IFNγ/PMA cocktail. There was also an isomer‐dependent difference in the NfκB modulating activity, with αToc being the greatest followed by γToc and δToc (P<0.05). On the other hand, δToc was shown to further promote Nrf2 nuclear translocation, while αToc had no effect. To conclude, the antioxidative pattern exhibited by Toc isomers does not correspond to the anti‐inflammatory activity in Caco‐2 cells; a finding that is attributed to either a non‐antioxidant function of Toc isomers, or the formation of pro‐oxidants at high concentrations of Tocs.Grant Funding Source: UBC‐FNH vitamin research fund and NSERC
Renal Adaptation in Gestational Iron Deficiency
Authors: Sun Mary (Yue) , Woolley Joseph C , Drake Keri A , Siddappa Asha Jyothi M , Georgieff Michael K , Magness Ronald R , Kling Pamela J 
Published: June 2021

BackgroundSevere gestational iron deficiency (ID) can impair fetal growth and renal development, ultimately causing adult hypertension. Nephrogenesis continues until P7 in rats. Our aim was to examine rat kidney adaptations during gestational ID.MethodsFrom gestational day 2 to postnatal day (P)7, pregnant rats were fed IS iron sufficient (198 mg Fe/kg diet) or ID rat diet (<6 mg Fe/kg diet), with the biological lactating dam nursing the pups. At P7 all ID dams were fed IS diet. At P15 and P30, rats were weighed, blood was drawn, and tissues were harvested. Kidneys were weighed and fixed renal sections were blindly examined for radial glomerular counts (RGCs), glomerular size, cortical depth, glomeruli per cortical surface area and total glomerular planar surface area. P<0.05 was considered significant.ResultsAt P15, ID pups were 20% smaller than IS pups, but only 8% smaller at P30. The ratio of kidney/rat weight was similar in all groups, except higher in P15 ID. At P15, hematocrit was lower in ID than IS, but not at P30. Glomerulogenesis was altered by gestational ID. Compared to P15 IS, RGCs in P15 ID were lower, mean glomerular size smaller, cortical depth shorter, glomerular density greater, and glomerular planar surface area lower. Microscopic renal morphometric parameters were normalized by P30.ConclusionGestational ID caused newborn anemia, growth restriction, with smaller and more‐dense glomeruli. The kidneys adapted to equalize glomerular density and filtering area, in contrast to published work in adult offspring of gestation ID. Delayed cessation of nephrogenesis may hold potential clues to understanding fetal renal adaptation to tissue iron depletion.UW Department of Pediatrics and UW Graduate School, Meriter Foundation, Minnesota Viking Children's FundGrant Funding Source : UW Department of Pediatrics and UW Graduate School, Meriter Foundation, Minnesota Viking Children's Fund
454 Pyrosequencing reveals a beneficial shift in fecal microbiota of healthy adult men consuming polydextrose or soluble corn fiber
Authors: Hooda Seema , Boler Brittany M Vester , Serao Mariana C Rossoni , Staeger Michael A , Boileau Thomas W , Dowd Scot E , Fahey George C , Swanson Kelly S 
Published: June 2021

The objective of the study was to test the impact of polydextrose and soluble corn fiber on the composition of the human gut microbiota using 454 pyrosequencing. Healthy adult males (n = 20) were enrolled in a randomized, double‐blind, placebo‐controlled crossover study. Subjects consumed 3 treatments (snack bars) containing either no supplemental fiber (NFC), polydextrose (PDX; 21 g/d), or soluble corn fiber (SCF; 21 g/d) for 21 days. Fecal samples were collected on day 16–21; DNA was extracted, followed by amplification of the V4–V6 region of the 16S rRNA gene for 454 pyrosequencing. The consumption of PDX and SCF led to an increase (P<0.05) in the families of Clostridiaceae and Veillonellaceae, and a decrease in Eubacteriaceae. The abundance of Faecalibacterium, Phascolarctobacterium, and Dialister was increased (P<0.05) in response to PDX and SCF intake, whereas Lactobacillus was higher (P<0.05) only after SCF intake. In contrast, PDX and SCF intake led to a decrease (P<0.05) in Eubacterium, Ruminococcus, and Bifidobacterium. Faecalibacterium prausnitzii was increased (P<0.05) by consumption of both fibers. The principal component analysis clearly indicated distinct clustering of individuals consuming novel fibers as compared to those consuming NFC. In conclusion, data demonstrated a beneficial shift in the gut microbiome of adults consuming PDX and SCF.Grant Funding Source: General Mills, Inc., Minneapolis, MN
Fatty Acid Binding Protein 4‐deficient Mice are Protected from Oxygen‐induced Retinal Neovascularization
Authors: Saint-Geniez Magali , Ghelfi Elisa , D'Amore Patricia , Hotamisligil Gökhan , Cataltepe Sule 
Published: June 2021

Fatty acid binding protein 4 (FABP4) is a member of the FABP family, which consists of highly conserved proteins that function as chaperones for free fatty acids. FABP4 plays a critical role in maintenance of glucose and lipid homeostasis as well as in the regulation of inflammation. Initially, FABP4 was thought to be expressed primarily by adipocytes and macrophages. We recently determined that FABP4 is also expressed in certain endothelial cells (ECs) where it plays a pro‐angiogenic role. The goal of this study was to determine whether FABP4 plays a role in oxygen‐induced retinal neovascularization.We induced oxygen‐induced retinopathy (OIR) by exposing pups to 75% oxygen between postnatal (P) days 7 and 12. FABP4 mRNA and protein levels were significantly increased during OIR. Immunostaining revealed that FABP4 was strongly expressed in pathological neovessels but absent in normal retinal vessels. In addition, both the neovascular and avascular areas of FABP4−/− retinas were significantly reduced at P17 compared to WT. The effect of FABP4 deficiency on OIR appears independent from macrophages recruitment.The observations that FABP4‐deficient mice are significantly protected from OIR and that FABP4 expression is restricted to neovascular tufts suggests that FABP4 inhibition may be a potential therapeutic target for proliferative retinopathies.This project is funded by the NEI grant 1R21EY021873‐01.
Inhibition of Myeloperoxidase by a Carbon Monoxide‐Releasing Molecule, CORM‐3
Authors: Patterson Eric Kenneth , Serzawa Fukashi , Capretta Alfredo , Fraser Douglas D , Potter Richard F , Cepinskas Gediminas 
Published: June 2021

Carbon monoxide (CO)‐releasing molecules (CORMs) have recently been shown to suppress inflammation by interfering with neutrophil function. However, the mechanisms are not completely understood. Neutrophilic myeloperoxidase (MPO) is known to induce tissue damage through: 1) the direct oxidation and/or 2) through the hypohalous acid‐dependent oxidation of targets.We hypothesized that CORM‐released CO inhibits MPO activity and thereby reduces neutrophil‐associated injury.In these studies, we used a water‐soluble, ruthenium‐based CORM (CORM‐3) that we synthesized and known to suppress inflammation. In vitro assays were used to study CO release under conditions relevant to inflammation. Further studies investigated CORM‐3's ability to inhibit total MPO activity as well as the activity of the peroxidation and halogenation components.Results indicate that CORM‐3‐released CO inhibited total MPO activity in a dose‐dependent manner. Furthermore, both the peroxidation and halogenation activities of MPO were inhibited by CORM‐3 in a dose‐dependent manner. On the contrary, control molecules; inactive CORM‐3 (a CORM lacking CO), or RuCl3 were less effective.In summary, CORM‐3‐derived CO inhibits MPO activity and therefore may suppress neutrophil‐induced tissue damage. (HSFO NA6914 and LHRI IRF‐025‐09)
Expression of pentraxin 3 in the lungs of human, horse, cattle and pig
Authors: Soron Michelle , Singh Baljit 
Published: June 2021

Bacterial lung diseases cause significant mortality and morbidity, causing enormous economic damage to the animal industry and cost billions of dollars in human health care. The innate immune system plays a critical role in the initiation of immune response in the lung. Pentraxin 3 (PTX3) is an acute phase protein that is produced at sites of inflammation by many cell types upon stimulation by proinflammatory cytokines, and agonists such as endotoxins. PTX3 recognizes and binds to many pathogens, activates the complement cascade, and has a role in the clearance of apoptotic and necrotic cells. Because there are very few data on the expression of PTX3 in the lungs, we examined PTX3 expression in normal and inflamed lungs of the horse, pig, human, and cattle using light and electron microscopic immunochemistry. We show PTX3 staining in bronchial epithelial cells and vascular endothelium in normal and inflamed lungs. Alveolar macrophages and inflammatory cells recruited into the lungs of bacteria‐infected animals stain intensely for PTX3. Immuno‐gold electron microscopy on horse, and calf lungs showed PTX3 in the nuclei, cytoplasm, and vesicular organelles of alveolar macrophages, endothelial cells and pulmonary intravascular macrophages. These data show PTX3 is expressed in normal lungs and its expression is increased in inflamed lungs.Grant Funding Source: Alberta Livestock and Meat Agency
EFFECT OF TIBOLONE ON MILD COGNITIVE IMPAIRMENT IN POSTMENOPAUSAL PATIENTS
Authors: Fernández-Hernández Said , Olivares-Corichi Ivonne Maria , Jimenez-Zamarripa Carlos Alberto , Rivera-Garcia Carlos , Calzada-Mendoza Claudia Camelia 
Published: June 2021

OBJECTIVETo evaluate the effect of tibolone on mild cognitive impairment in postmenopausal patients, the concentration of malondialdehyde/4‐ hidroxinonenal and anthropometric parameters.METHODSTwenty menopausal patients (50–55 years old) were included. The determinations were clinical history, body mass index, waist‐hip ratio, percentage of body fat, concentration of malondialdehyde/4‐ hidroxinonenal, and the cognitive function; which were evaluated before and 3 months after of treatment with tibolone.RESULTSTibolone improved cognitive function in 77% of patients who had mild cognitive impairment baseline. Also reduced damage to lipid marker for oxidative stress (17 vs 11 nM MDA‐HNE before and after treatment, respectively), but anthropometric parameters were unchanged.The correlation analysis showed that at low lipid damage is a higher score in memory.CONCLUSIONSTibolone decreased mild cognitive impairment and the concentration of markers of lipid damage by oxidative stress, but did not reduce body mass index, waist‐hip index and fat percentage.
Molecular Determinants of Reactivation Potency for Novel, Efficacious, Centrally Active Oxime Reactivators of Phosphylated Acetylcholinesterase
Authors: Radic Zoran , Sit Rakesh K , Kovarik Zrinka , Berend Suzana , Garcia Edzna , Zhang Limin , Amitai Gabriel , Fokin Valery V , Sharpless K Barry , Taylor Palmer 
Published: June 2021

We present here systematic structural optimization of uncharged but protonated N‐substituted 2‐hydroxyiminoacetamide reactivators of phosphylated human acetylcholinesterase (hAChE) intended for reactivation of organophosphate (OP) inhibited hAChE in the CNS. Starting with library of 138 uncharged reactivators we identified the initial lead, RS41A and refined its structure culminating in the azepine analogue RS194B, several‐fold enhanced for reactivation of OP‐hAChE conjugates formed by sarin, cyclosarin, VX, paraoxon and tabun. Detailed in vitro reactivation kinetics of RS194B revealed superiority over standard, pyridinium, reactivator antidote 2PAM and approached the potency of bisquaternary, bipyridinium dioxime MMB4. The pH dependence studies of UV, 1H NMR and oximolysis properties of lead oximes revealed pKa values of their ionizable groups in the range from 8.1 (for 2PAM) to 8.9 (for RS41A and RS194B). The low toxicity of RS194B (LD50=500 mg/kg) in mouse animal model in combination with its enhanced intrinsic reactivity resulted in great improvement of its therapeutic properties compared to RS41A, and standard oxime 2PAM. The improvement was particularly noticeable when pretreatment of mice with RS194B before OP exposure was combined with RS194B reactivation therapy following the OP insult.Supported by the CounterACT Program, NIH OD, and the NINDS, Grant Number U01 NS058046.
THE EFFECT OF NORMOBARIC OXYGEN ON THE INJURY INDUCED BY FOCAL CEREBRAL ISCHEMIA IN RATS VIA HIF‐1‐NOTCH SIGNAL PATHWAY
Authors: chen chunhua , Zhang Weiguang , Yang Lei , Wang Ke , zhou Changman 
Published: June 2021

ObjectiveTo investigate the effect of pretreatment of inhalation of normobaric oxygen(NBO) on the injury induced by focal cerebral ischemia via HIF‐notch pathway.MethodsMale SD rats were randomly divided into four groups: Control (sham surgery), Middle Cerebral Artery Occlusion and Reperfusion(MCAO), MCAO pretreated with Normobaric Oxygen (NBO), MCAO with NBO injected with 2ME2. 2ME2 was injected intraperitoneally at 1h before the inhalation of NBO. NBO was inhaled for 4h a day and for 6d continuous. We observed the neurological deficits in different groups. Rats were sacrificed at 24h for TTC staining, western blot, nissl and immunohistochemical staining.ResultsNBO pretreatment improved neurological deficits, reduced the infarct volume (P<0.05), inhibited the neuronal deformation shown by nissl staining and increased the expression of HIF‐1¦Á and Notch1 detected by Western Blot and immunohistochemical staining. But all the improvement were lessened by the 2ME2 injection.ConclusionNBO pretreatment may protect brain from cerebral ischemic injury via HIF‐Notch1 signal pathway.
Effect of a diet rich in fat and/or fructose on potassium channel gene expression in rat small mesenteric artery
Authors: Jensen Lars Jørn , Sorensen Charlotte Mehlin , Plogmark Oscar , Holstein-Rathlou Niels-Henrik , Salomonsson Max 
Published: June 2021

We tested if arterial K+ channel gene expression is reduced under dietary conditions mimicking the metabolic syndrome. Male Sprague‐Dawley rats were fed high‐fat + high‐fructose (HFF; N=4) or high‐fructose (HF; N=4) diet from 4 to 32 weeks (wks) of age. Age‐matched control rats (CTRL) were fed normal chow (N=4 in each group). Systolic blood pressure (SBP) was measured using the tail cuff method. mRNA expression of K+ channels in mesenteric arteries was measured using quantitative real‐time polymerase chain reaction (Q‐PCR). At 32 wks body weight (BW) was increased in HFF (639±37g; P<0.05) compared to CTRL (522±22g), whereas BW was similar in HF (574±35g) and CTRL (564±15g). Average SBP through wks 10–32 was higher in both HFF and HF rats compared to their respective CTRL (HFF: 134±4 mmHg vs. 121±2 mmHg, P<0.05; and HF: 131±5 mmHg vs. 118±2 mmHg, P<0.05). In small mesenteric artery of HFF rats, mRNA expression of SK3 was reduced to 59% of that in CTRL (P<0.05) and KV1.5 was reduced to 73% of that in CTRL (P<0.01), while Kir2.1, Kir6.1, BKCa, IKCa, KV1.2 and KV7.4 expression was unchanged. HF diet did not significantly change K+ channel expression. We conclude that reduced expression of SK3 and KV1.5 channels might partially explain the increased SBP in metabolically challenged rats fed a diet rich in fructose + fat but not in those fed high‐fructose only.Grants: Danish National Research Foundation (F.); Danish Heart F.; Lundbeck F.
Autonomic Impairment During Severe Hemorrhage in Obese Zucker Rats
Authors: Clemmer John S. , Xiang Lusha , Lu Silu , Lee Lynn , Hester Robert L. 
Published: June 2021

Obesity is characterized by impaired autonomic activity which may adversely affect cardiovascular responses under pathological conditions such as acute hypovolemia. We hypothesize that obesity can impair acute blood pressure regulation during hemorrhage via lack of sympathetic effectiveness and impaired neural reflexes. Severe hemorrhage (a loss of 35% of total blood volume) was induced via femoral catheter (approximately ~0.7ml/min, 11–12 minutes) in conscious lean (LZ) and obese Zucker rats (OZ) (11–12 weeks). Blood pressures and heart rate were monitored during hemorrhage and during 30 minutes of recovery. Control blood pressures and heart rates were not statistically different between LZ and OZ. During hemorrhage blood pressure in the OZ dropped below basal after a 5% loss (Figure 1), while a decrease in blood pressure was not evident until 15% loss of total blood volume in LZ. An elevation in heart rate was sustained until 25% blood loss in LZ but only until 5% blood loss in the OZ (Figure 2). Blood pressure was partially compensated 30 minutes after the completion of hemorrhage in both LZ and OZ, but the OZ blood pressure was significantly lower than the LZ. During the first 5 minutes after completion of the hemorrhage heart rate was decreased in both OZ and LZ with a significantly greater decrease with OZ. In addition, the heart rate was elevated in the LZ at the end of the 30 minute recovery but remained decreased in OZ (Figure 2). Our results suggest that, in response to acute hemorrhage, the compensatory mechanisms mediated by sympathetic activation such as increase in peripheral resistance and tachycardia are blunted in OZ, resulting in increased vulnerability to volume loss and impaired recovery.Supported by NIH HL‐51971 and HL‐89581.
Estimating peripheral blood pressure from central blood pressure by a transfer function method
Authors: Rose William C. , Schell Kathleen A. , DiSabatino Angela , Stillabower Michael E. 
Published: June 2021

ObjectiveDetermine whether blood pressure measured by a cuff on the forearm could be predicted better by upper arm cuff pressure or by radial pressure estimated by a transfer function method from the ascending aortic pressure wave.Subjects32 adults undergoing cardiac catheterization.MethodsBlood pressure was measured by cuffs on the forearm and upper arm and by a catheter in the ascending aorta. A transfer function was used to predict radial artery blood pressure from the ascending aortic pressure waveform. Regressions were computed between upper arm pressure measured by cuff and forearm pressure measured by cuff, and between predicted radial artery pressure and forearm pressure measured by cuff.ResultsThe transfer function method did not predict forearm systolic pressure as well as the upper arm cuff did (r=0.76 for the former, r=0.89 for the latter). For diastolic pressure and mean pressure, the transfer function method predicted slightly less well than the upper arm cuff (r=0.83 vs. r=0.87 for diastolic; r=0.77 vs. r=0.80 for mean).ConclusionsThe transfer function method does not predict forearm cuff blood pressure better than an upper arm cuff measurement. Supported by the University of Delaware Research Foundation.
Role of miRNAs for vascular smooth muscle mechano‐sensing and contractile function
Authors: Albinsson Sebastian 
Published: June 2021

The phenotype of smooth muscle cells is orchestrated by regulation of mRNA and protein expression, which is partly controlled by mechanical stimuli. miRNAs are small non‐coding RNAs that participate in the regulation of mRNA and protein expression and are now known to be involved in smooth muscle differentiation and growth.The objective of this study was to investigate the role of miRNAs for smooth muscle mechano‐sensing and contractile function.The importance of miRNAs was identified by stretch or pressurization of vessels from Dicer KO and control mice. Dicer is an essential for the formation of most mature miRNAs. We found that stretch‐sensitive contractile differentiation was reduced in Dicer KO portal veins. Furthermore, myogenic tone and pressure induced signalling events were abolished in pressurized arteries from Dicer KO mice. Finally, we found a reduced expression of L‐type calcium channels in Dicer KO vessels, which may be an important mechanism behind these effects.In conclusion, miRNAs play an important role for vascular mechano‐sensing and contractile function.This study is primarily funded by the Swedish Heart and Lung Foundation and the Crafoord Foundation