bluuebunny/crossref_metadata_2025_split huggingface dataset:
HEPATOPROTECTIVE EFFECT OF SILICA HYDRIDE ON CARBON TETRACHLORIDE‐INDUCED HEPATIC INJURY IN RATS
Authors: Mendieta Jessica Elena , Correa José , Trujillo José , Rosales Martha 
Published: June 2021

Reactive oxygen species (ROS) have been proven to cause numerous cellular anomalies, which cause oxidative stress. Taking into account that the most endogenous and exogenous antioxidants are not enough effective as reducing agents and as ROS selective scavengers, an anionic hydride organosiloxane, commonly named silica hydride (SiH−), was previously evaluated in vitro. However, none research had been done to prove its antioxidant and protective effects in vivo. For this reason, this work was aimed to demonstrate it suggesting its possible mechanism of action.The results of the present study demonstrate that the protective effect of SiH− is dose‐dependent. Pre‐treatment of Sprague‐Dawley rats with dosages of 180 and 200 mg/kg showed the better protection against CCl4‐induced hepatotoxicity. Lipid peroxidation and cytochrome P‐450 activity significantly decreased in relation to that of controls. In contrast, glutathione content, glutathione peroxidase and glutathione reductase activities significantly increased. The lower serum levels of alanine and aspartate amino transferases were restored. Histopathological studies confirm the protective effect of SiH−. In conclusion, this model in vivo and the different assays confirm that the mechanism of hepatoprotective action of SiH− may be due to its antioxidant and radical scavenger activities.
Polyphenols, Carotenoids, Tocopherols and Antioxidant Activity in Different Varieties of Angelica keiskei and Glycine max
Authors: Chun Hye‐Kyung , Li Lei , Aldini Giancarlo , Park Ki‐Moon , Cho Soo‐Muk , Chen Chun Yen Oliver , Blumberg Jeffrey B , Russell Robert M , Yeum Kyung‐Jin 
Published: June 2021

The antioxidant content and activity as well as the stability of different varieties of Angelica keiskei (n = 3), and Glycine max (n = 5) were determined. Angelica keiskei, a dark green leafy vegetable, was lyophilized; and Glycine max, black soybeans, were roasted at 125°C for 2 min, milled to a powder and stored at room temperature, 4°C or −80°C for 4 mo. Carotenoids, tocopherols, and ascorbic acid, were analyzed by HPLC systems, total phenols by spectrophotometry, and antioxidant activity by fluorometry. Polyphenols in Angelica keiskei were further characterized by LC‐ESI‐MS/MS. A range in the content of lutein (205–265 μg/g dry wt), trans‐β‐carotene (103–130 μg/g dry wt), and total phenols (8.6–9.7 mg/g) was observed among three different varieties of Angelica keiskei. LC‐ESI‐MS/MS analysis identified that chlorogenic acid, chalcones and the glucosides of luteoline & quercetin as the major polyphenols in Angelica keiskei. Glycine max contained γ‐tocopherol and lutein at 82–133 and 6.5–14.6 μg/g dry wt, respectively. Major phytonutrients except for β‐carotene and antioxidant activity in lyophilized Angelica keiskei and Glycine max were stable up to 4 mo at the tested temperatures. Thus Angelica keiskei and Glycine max are stable sources of phytonutrients with their concentration dependent upon the variety.[Supported in part by USDA #58‐1950‐7‐707, USA & BioGreen 21 Program (Code #20070301034009) RDA, Korea]
Genistein, daidzein, and equol increase quinone reductase activity and protein in Hepa‐1c1c7 cells
Authors: Froyen Erik , Steinberg Francene 
Published: June 2021

Soy protein and isoflavones, genistein (G) and daidzein (D), are associated with protection against the risk of cancer. One postulated mechanism is modulation of phase I and II biotransformation enzymes. The objective of this study was to analyze phase II enzyme Quinone Reductase (QR) activity, protein, and RNA in Hepa‐1c1c7 cells treated with G, D, and equol (E), a daidzein metabolite. We hypothesize that G, D, and E increase QR enzyme activity, protein, and RNA via estrogen receptor beta binding and interacting with the QR antioxidant response element. Hepa‐1c1c7 cells were treated with DMSO (0.1% v/v), β‐naphthoflavone (positive control at 1 μM), and G, D, and E at concentrations of 1, 5, and 25 μM. After 24 hours of treatment (results expressed as treated/control ratios), G (1.32, 1.42, and 1.75), E (1.65, 1.58, and 1.65), and D (1.55 at 1 μM) increased QR activity compared to the DMSO treated cells (n = 3 per group) (P<0.05). After 48 hours, G (1.3 and 1.6), D (1.39 and 1.34), and E (1.46 and 1.55) at 5 and 25 μM concentrations increased QR activity (n = 12 per group) (P<0.05). Furthermore, G, D, and E increased QR protein in 25 μM treated cells. Future approaches include use of chromatin immunoprecipitation (ChIP) assay to determine the mechanism of isoflavone stimulated increase in QR expression. In conclusion, G, D, and E significantly increase QR activity and protein in Hepa‐1c1c7 cells.Support: Departmental funds.
Anemia and malnutrition is equal in children included and not included in the Oportunidades supplementation programme in Guanajuato Mexico
Authors: Delgado Luz María , García Olga Patricia , Caamaño María del Carmen , Rosado Jorge Luis 
Published: June 2021

The objective of the present study was to compare nutritional status and anemia in children who have been part of the Oportunidades program in Mexico and consumed a fortified porridge (N=87) with similar children who have not been included in the program (N=89). The study was carried out in infants (35 ± 13 mo) and both groups were from the same rural communities in the state of Guanajuato. Weight and height were measured in all subjects, and a fasting blood sample was taken for the determination of hemoglobin. The results are shown in the table.No differences were found between both groups in anemia or any of the growth variables. In conclusion, the inclusion of children in the Oportunidades national program including the intake of the fortified porridge to infants of these communities does not have a significant impact in the nutritional status, growth and anemia.
Morphometric Evaluation of Tongue Epithelium in Experimental Chromium Administration
Authors: Farinha Rodrigo , Rafael Ana I.V. , Falacho Rui , Alpoin Carmen , Cabrita A.M. Silvério 
Published: June 2021

Recent reports alert to the presence of chromium in drinking water, mainly related with industry contamination. The hexavalent form is a carcinogenic for lab animals. In this study we make a morphometric evaluation of tongue epithelium in the experimental administration of chromium per os.We used 20 animals, distributed into two groups: one kept with no manipulation (control) and one submitted to the administration of drinking water contaminated with chromium, 20 ppm (test). After 30 weeks all the animals were sacrificed and the necropsy was performed, collecting the tongue for histology. The histological slices were observed at three different levels and analyzed using Sigma Scan Pro®. Taking the epithelium area (EA) and the total area of the tongue at each level (TA), we calculated the ratio: EA/TA.We observed in the test group some cases of focal increased thickness of the epithelium with expressive endophytic growth. No neoplastic lesions were observed. The calculated ratio didn't shown significant differences between the two groups, for a 95% confidence interval.According to these results, the administration of chromium in the drinking water may be responsible for focal tongue morphologic changes with an endophytic proliferation of epithelial tissue.
Expression of BRCA1 and FAC1 in primary sporadic breast cancers.
Authors: White Kristen K. , Wells Wendy A. , Bowser Robert , Tsongalis Gregory J. , Coleman William B. 
Published: June 2021

We have previously described a +ACA BRCA1 promoter polymorphism that creates a FAC1 transcriptional repressor binding site (AACAACAC), which may confer FAC1‐mediated transcriptional repression (depending on the BRCA1 promoter genotype). To explore the relationship between BRCA1 and FAC1 expression in primary breast cancers, we performed immunostaining on 69 luminal A and B subtype sporadic breast cancers (ER+, PR+, HER2+/−). Most tumors are positive for BRCA1 expression (40/69, 58%), while a subset express reduced BRCA1 levels (29/69, 42%). The majority of these tumors (64/69, 93%) are positive for FAC1 expression: 27/64 (42%) express cytoplasmic FAC1 (cFAC1), 23/64 (36%) express both cFAC1 and nuclear FAC1 (nFAC1) and 14/64 (22%) express nFAC1 only. Among tumors with reduced BRCA1 expression, 55% (16/29) are positive for nFAC1 expression (which represents 43% (16/37) of nFAC1 expressing tumors that have reduced BRCA1 protein expression). This data suggests that most primary breast tumors are positive for FAC1 expression, and that 58% of FAC1 expressing tumors have some degree of nuclear FAC1 expression. It is intriguing to speculate that nFAC1 may modify gene expression in breast tumors, resulting in repression of normal BRCA1 expression, and contributing to breast carcinogenesis.Support: NIH CA78343, Komen Foundation BCTR0100575, Friends For an Earlier Breast Cancer Test.
Effects of Helicobacter typhlonius and H. rodentium Infections in IL‐10‐deficient Mice
Authors: Chichlowski Maciej , Sharp Julie M. , Vanderford Deborah A. , Myles Matthew H. , Hale Laura P. 
Published: June 2021

Murine intestinal infections with Helicobacter typhlonius and/or H. rodentium are endemic within many research facilities. This study was designed to analyze effects of infection with these two Helicobacter species in the C57BL/6 IL‐10‐deficient (IL‐10−/−) mouse. Adult IL‐10−/− mice experimentally infected with H. rodentium and/or H. typhlonius developed inflammatory bowel disease (IBD), with the severity of inflammation at 11 weeks post‐infection being: non‐infected (no inflammation) < H. rodentium < H. typhlonius < mixed H. rodentium + H. typhlonius. Helicobacter DNA was detected in gastrointestinal and reproductive organs of infected mice by quantitative real‐time PCR. Infected mice also showed significant differences in pregnancy rates, number of pups born, and pups surviving to weaning compared with non‐infected controls. Treatment with 3 mg amoxicillin, 0.5 mg clarithromycin, 1 mg metronidazole, and 20 μg omeprazole per 5 g chow eradicated Helicobacter infection, ameliorated established IBD, and increased pregnancy rates and pup survival. Results demonstrate the pathogenicity of H. rodentium in a mono‐infection model and suggest a complex role of both Helicobacter and other intestinal microbiota in reproductive success and the development of IBD in susceptible hosts.This work was supported by NIH grant # CA115480.
Expression of neuregulin‐1 and ErbB‐receptors mRNAs is modulated by denervation and reinnervation in adult rat skeletal muscles
Authors: Geuna Stefano , Nicolino Silvia , Raimondo Stefania , Tos Pierluigi , Perroteau Isabelle 
Published: June 2021

The Neuregulin/ErbB signaling pathway plays and important role in the neuromuscular system. The aim of the present study was to investigate by immunohistochemistry, RT‐PCR and Western blotting analyses, in an in vivo model of adult skeletal muscle denervation/reinnervation, if the expression of Neuregulin‐1 (NRG1) and ErbB receptors is regulated by the innervation condition.Results showed that denervation of flexor digitorum muscles of the rat forelimb by median nerve transection led to a significant up‐regulation of the α, but not β, isoform of NRG1, as well as of ErbB2, ErbB3 and ErbB4‐cyt1 isoform. Reinnervation, i.e. the arrival of regenerated axons after median nerve surgical reconstruction, induced a prompt down‐regulation of all messengers of the NRG1/ErbB system. Altogether, our results describe the variations of the NRG1/ErbB system in skeletal muscles and suggest the existence of a NRG1‐mediated autocrine and/or paracrine trophic loop that is activated after muscle denervation. This myotrophic loop can represent a promising therapeutic target for the prevention of various muscle diseases.Financial support: Italian M.U.R. (PRIN2005 fund) and Regione Piemonte (CIPE fund).
Stem cell mobilization and vasculogenesis stimulated by lactate and oxygen
Authors: Milovanova Tatyana N. , Sorokina Elena M. , Bhopale Veena M. , Moore Jonni S. , Hunt Thomas K. , Velazquez Omaida C. , Thom Stephen R. 
Published: June 2021

This investigation assessed the effects of lactate and hyperoxia on recruitment and differentiation of stem/progenitor cells (SPCs). Within 18 hours after Matrigel plugs were implanted subcutaneously in mice, over one million CD34+ SPCs were recruited. Including a lactate source in Matrigel increased SPCs by 3.6‐fold at 18 hours and 5.8‐fold at 5 days. Lactate accelerated CD34+ cell differentiation based on surface marker expression, development of intricate vascular channels, and a higher fraction in the S and G2‐M phases of the cell cycle. If mice were intermittently exposed to hyperbaric oxygen, there were increased numbers of CD34+ cells in blood and Matrigel, accelerated differentiation and more complex vascular channels. Combining a lactate source and hyperoxia had an additive effect on CD34+ cells. If the Matrigel contained oxamate, a lactic dehydrogenase inhibitor; or antibodies that neutralize vascular endothelial growth factor or stromal derived growth factor, CD34+ cell recruitment and differentiation were inhibited. Hypoxia inducible factor‐1α (HIF‐1) was elevated in CD34+ cells from lactate‐supplemented versus un‐supplemented Matrigel. Hyperbaric oxygenation caused significant elevations of HIF‐1 in CD34+ cells in bone marrow, blood and Matrigel.Conclusion: SPCs influence their own homing response by metabolizing lactate and generating growth factors to mediate progressive SPCs mobilization, recruitment and differentiation into vascular channels [N00014‐06‐1‐0363].
Accelerated Atherosclerosis in Low Density Lipoprotein Receptor Deficient Mice Lacking the Membrane Complement Regulator CD59
Authors: Yun Sheng , Leung Viola , Botto Marina , Boyle Joseph , Haskard Dorian 
Published: June 2021

Background: CD59 is a membrane glycoprotein that inhibits terminal complement pathway C5b‐9 assembly. Here, we tested the hypothesis that CD59 limits the proinflammatory effects of complement activation in atherosclerosis.Methods and Results: CD59 gene targeted mice (CD59a−/−) mice were crossed with Ldlr−/− mice to give double knock‐outs (DKO), and studied aged 22 weeks. Immunocytochemical staining showed CD59 on endothelial cells, vascular smooth muscle cells (VSMC) and macrophages in Ldlr−/− mice, with absent staining in DKO. DKO had more extensive en face Sudan IV staining of thoraco‐abdominal aorta than Ldlr−/− single knock‐outs, both following a normal chow (6.51 + 0.36% vs 2.63 + 0.56%, p<0.0001) or a high fat diet (17.05 + 2.15% vs 7.69 + 1.17%, p<0.02). Accelerated lesion formation in DKO mice was associated with significantly increased complexity of lesions in the aortic root, as assessed by increased VSMC number and fibrous caps development. The acceleration of atherosclerosis in DKO mice was associated with significantly greater deposition of C5b‐9, both following a chow or a high fat diet.Conclusion: The acceleration of lesion formation in the absence of CD59 provides definitive evidence for complement activation in the Ldlr−/− mouse model and underlines the importance of CD59 in protection from the proatherogenic effects of the terminal complement pathway.Funded by the British Heart Foundation
Decay‐Accelerating Factor plays a critical atheroprotective role in Low Density Lipoprotein deficient (ldlr−/−) mice
Authors: Leung Viola WY. , Yun Sheng , Mason Justin , Song Wenchao , Botto Marina , Boyle Joseph , Haskard Dorian 
Published: June 2021

Background: The GPI‐anchored membrane glycoprotein Decay‐Accelerating Factor (DAF, CD55) inhibits complement activation by downregulating C3 and C5 convertases. We asked whether DAF × LDLR double knock‐out (DKO) mice are protected from atherosclerosis.Methods and Results: Immunostaining showed expression of DAF by endothelial cells, macrophages and vascular smooth muscle cells in ldlr−/− but not in DKO. At 22 weeks on a chow diet, DKO mice had more en face Sudan IV staining of thoracoabdominal aorta than LDLR single knock‐outs (4.66 ± 0.63% vs 2.85 ± 0.34%, mean ± SEM, p<0.05). Accelerated lesion formation in DKO mice was also evident in aortic roots, with lesions being larger (76.16 ± 9.53 × 103 μm2 vs. 29.42 ± 3.83 × 103 μm2, mean ± SEM, p<0.0005) and more complex (vascular smooth muscle cell content 13.86 ± 5.82 % vs. 2.23 ± 1.54 %, p<0.0005). DKO mice had increased aortic root C3d staining (% lesion positive for C3d 11.5 ± 1.3% vs 3.0 ± 0.2%, p < 0.001), and higher levels of IL1β and TNFα (p<0.01 each).Conclusion: Our data indicate that DAF plays a critical role in regulating C3 activation in the arterial wall. Effective complement regulation enables the protective actions of the classical complement pathway on debris clearance to occur whilst reducing deleterious proinflammatory downstream effects of C3 activation.Funded by the British Heart Foundation
Food restriction alters pramipexole‐induced yawning, hypothermia, and locomotor activity in rats: Evidence for sensitization of D2, but not D3 receptor‐mediated effects
Authors: Collins Gregory Thomas , Calinski Diane M , Woods James H 
Published: June 2021

It has been well established that food restriction enhances sensitivity to the reinforcing effects of drugs of abuse, and that food restriction alters a variety of behavioral and pharmacological responses to dopaminergic agonists. Evidence from behavioral and molecular studies suggests that augmented dopaminergic responses observed in food‐restricted animals result from a sensitization of the D2 receptor, however, little is known about how food restriction affects the D3 receptor. These studies were aimed at defining the effects of food restriction on D2 and D3 receptor function by assessing pramipexole(PPX)‐induce yawning, penile erection (PE), hypothermia, and locomotor activity in free‐fed and food‐restricted rats. Food restriction resulted in a suppressed level of PPX‐induced yawning, a sensitized hypothermic response, and an enhanced locomotor response to PPX; there was no effect on PPX‐induced PE. In food‐restricted rats, the D3‐selective antagonist, PG01037, inhibited PPX‐induced yawning and PE while the D2‐selective antagonist, L‐741,626, restored PPX‐induced yawning to free‐fed levels. These results suggest that food restriction sensitized rats to the D2‐mediated effects of PPX while having no effect on the D3‐mediated effects of PPX.Supported by grants DA20669 & F013771 through NIDA
Stereochemical aspects regarding the detoxification of the 4‐hydroxynonenal enantiomers by human glutathione S‐transferase A4‐4
Authors: Balogh Larissa Maria , Roberts Arthur G , Atkins William M 
Published: June 2021

4‐Hydroxynonenal (HNE) is a toxic unsaturated aldehyde generated during lipid peroxidation that has been implicated in pathological states such as neurodegenerative diseases and cancer. HNE may spontaneously react with glutathione (GSH) to form a conjugate (GSHNE) possessing three chiral centers in the cyclic hemiacetal portion of the structure. The aim of this study is to investigate the significance of the chirality of HNE and GSHNE with respect to metabolism. Three of the GSHNE diastereomers were isolated and sets of distance restraint estimates obtained from rotating‐frame Overhauser enhancement NMR experiments were incorporated into Crystallography and NMR System‐based simulated annealing structure determinations on all the potential stereochemical configurations for GSHNE. Relative energies calculated for each combination were then used to select the best fit stereochemical configurations for each diastereomer. Physiologically, GSTA4‐4 is the predominate enzyme responsible for the conjugation of HNE and GSH. LC/MS analyses using the racemic‐ and enantioisomeric‐HNE substrates demonstrated that GSTA4‐4 conjugates GSH to HNE in a stereoselective manner that is not observed in the spontaneous reaction. Furthermore, similar experiments conducted to compare the different GST isoforms revealed that GSTA1‐1 and GSTP1‐1 are less stereoselective than GSTA4‐4.Supported by NIH grant GM32165.
Distinct pharmacological activities associated with naturally occurring splice variants of the human constitutive androstane receptor
Authors: DeKeyser Joshua G , Bryant Sharon D , Omiecinski Curtis J 
Published: June 2021

The constitutive androstane receptor (CAR/CAR1, NR1I3) responds to chemical modulators to regulate the expression of many hepatic genes, including those related to all three phases of xenobiotic biotransformation. Recent reports from our laboratory have focused on functional analysis of human CAR variants produced by alternative mRNA splicing. In particular, CAR2 and CAR3 contain insertions of 4‐ and 5‐amino acids, respectively, within their ligand binding domains. Results obtained from specific, quantitative RT‐PCR assays demonstrated that the proportions of CAR1:CAR2:CAR3 transcript levels are relatively consistent among individual hepatocyte preparations derived from 7 different human donors. On average the CAR2 insertion occurred in 28.4% of CAR transcripts and the CAR3 insertion was found in 18.3%. Luciferase reporter/transcription assays were used to differentially assess the CAR variants’ ability to activate a promoter derived from the endogenous CYP2B6 target gene. Our results demonstrate that CAR2 possesses a distinct activation profile relative to the CAR1 ligands, (5‐β)‐pregnane‐3,20‐dione, CITCO, meclizine, and clotrimazole. These data are now being used to design pharmacophores for use in ligand‐based virtual screening studies to identify selective CAR2 ligands.Supported by NIH, GM66411.
The effect of chronic degradation of the endothelial glycocalyx on atherosclerosis progression in ApoE knockout mice
Authors: Meuwese Marijn Clara‐Maud , Stroes Erik Sjoerd Gerard , Vink Hans , van den Berg Bernard 
Published: June 2021

The protective barrier between flowing blood and the vessel wall is formed by endothelial glycocalyx.We investigated the effect of chronic damage to glycocalyx through enzymatic degradation of its major component hyaluronan on atherosclerosis progression.Male ApoE‐KO mice (14 wks) received 10 U/hr of active or inactivated hyaluronidase intravenously via an osmotic minipump for 4 wks, after being on a Western diet for 6 wks. Systemic glycocalyx volume (Vg) was estimated by tracer dilution techniques using labeled erythrocytes and 40kDa dextran. We are evaluating atherosclerotic lesions in the aortic root and arch.ApoE‐KO tolerated chronic infusion with hyaluronidase well. Within 4 wks Vg was reduced to 9.1 ± 8.9 ml/kg (n=11) as compared to Vg before infusion of 16.0 ± 4.8 ml/kg (n=12, p=0.03) and inactive hyaluronidase infusion of 12.1 ± 5.3 ml/kg (n=6, ns). Diet for 6 wks resulted in fatty streak formation within the aortic root (lesion area 0.5 ± 0.0 mm2). Infusion of hyaluronidase resulted in advanced lesions (area 1.3 ± 0.2 mm2) with intimal thickening, cholesterol accumulation and necrotic cores.These preliminary results suggest a possible association between reduced glycocalyx and atherogenic acceleration.Supported by NHF 2005T037 to H. Vink and 2006B08 to E. Stroes