bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cellular Damage Evaluation caused by Dental Bleaching Products – a pilot study
Authors: Marto Carlos Miguel , Laranjo Mafalda , Abrantes Ana Margarida , Lopes João Casalta , Gonçalves Ana Cristina , Ribeiro Ana Bela Sarmento , Cabrita António Silvério , Ferreira Manuel Marques , Botelho Maria Filomena , Carrilho Eunice 
Published: June 2021

Esthetic demands makes dental bleaching an increasingly requested therapy, however this is not a risk‐free procedure due to the cytotoxicity of whitening products. This work evaluates possible cytotoxic effect on cells caused by whitening products.We performed an in vitro study with human fibroblasts cell cultures, exposed at different concentrations of hydrogen peroxide and a commercially available bleaching product, with and without photo activation. Evaluation was made at 45 minutes and 24, 48 and 72 hours. Flow cytometry was also performed. The Mann‐Whitney test was used for statistical analysis.Recovery in cell viability is observed after 45min with the commercial product and only after 48 hours with hydrogen peroxide. Also, the application of hydrogen peroxide causes an increase in cell death by apoptosis, in production of intracellular peroxides and a decrease in mitochondrial membrane potential. The activating light alone causes an increase in cell death by apoptosis. These data present a p < 0.05 and a range of 95%.Decrease of cell viability was reversibly in all situations. Hydrogen peroxide and activating light have a cytotoxic effect on cell cultures, increasing cell death, unlike the commercial product tested, so we can hypothesize some protective effect by other components from commercial bleaching product. This results may be correlated with clinical findings namely hypersensitivity.
Application of Image‐Guided Coring as a new technique for targeting breast tumor tissue in molecular pathology
Authors: Montaser‐Kouhsari Laleh , Christensen Stephen , Knoblauch Nicholas W , Baker Gabrielle , Beck Andrew H 
Published: June 2021

BackgroundThere are several techniques available to sample tissue from archival formalin‐fixed paraffin‐embedded (FFPE) tissue blocks. However, current techniques are either extremely labor intensive or lack precision for accurately sampling small lesions. Herein, we explain a new image‐guided coring (IGC) technique to conquer these limitations for molecular analyses.DesignThe H&E slides were scanned by the whole slide digital panoramic scanner (3D‐Histech). Then, a pathologist selects regions of interest from these digital images using the Pannoramic Viewer Software package (3D‐Histech). This annotated slide is overlaid onto digital image of the FFPE block via TMA‐Master software (3D‐Histech) and a computer‐guided robotic arm is used to sample cores from the targeted regions of the FFPE tissue block. This selectively acquired tissue is then used for molecular analyses.ResultsWe applied IGC to 770 FFPE breast samples from the Nurses’ Health Study including 389 invasive carcinomas and 381 normal terminal duct lobular unit samples. The median concentration of extracted RNA in tumor and normal samples was 127 ng/ml and 23.31 ng/ml, respectively. A high success rate of adequate RNA extraction (20 ng/mL) from tumor and normal breast tissue via IGC was obtained (88.9% and 55.4%, respectively).ConclusionIGC is a robust new approach to obtain samples from FFPE blocks in large‐scale projects in molecular oncologic pathology. We applied this new method to accurately sample breast cancer and normal breast tissue from FFPE samples with high success rates. This method may prove generally useful for clinical molecular diagnostics as well as translational tissue‐based biomedical research.
Complement MAC expression in heart failure
Authors: Rietdorf Emily , Chow Sheryl , O'Barr Stephen 
Published: June 2021

Complement is expressed during acute myocardial infarction (AMI), but little is known of its involvement in the development of heart failure (HF).MethodsRats were induced with HF by occlusion of the LAD coronary artery, and then sacrificed four weeks later. Controls were given a sham operation with the same procedure minus the occlusion. Hearts were excised then homogenized in RIPA buffer. Western blots were run with C7 (Quidel) and C5b‐9 (Hycult) antibodies at 1:1000, secondary antibody at 1:5000, blocked with TBST + 5% milk.ResultsEight control samples vs. eight HF samples were evaluated. Both C7 and C5b‐9 levels in the HF samples were significantly increased in comparison with the controls.ConclusionsThese results demonstrate that complement is activated in our HF model, but more studies are needed to determine its specific role in HF pathology. Financial support was provided by the Drew Collaborative Grant # 12304P (SLC), GCRC LaBioMed #00543–38F (SLC), NIH R21DK070003–01A1, and Western University of Health Sciences MSPS Graduate Program (ER).
Pre‐TM4 residues of GluN2 subunits modulate the function of recombinant N‐methyl‐D‐aspartate (NMDA) receptors
Authors: Hughes Benjamin , Woodward John 
Published: June 2021

The N‐methyl‐D‐aspartate (NMDA) receptor is a ligand‐gated ionotropic receptor activated by the neurostransmitter glutamate and is essential to fast excitatory neurotransmission. NMDARs are heteromeric tetramers composed of obligate GluN1 subunits as well as GluN2 or GluN3 subunits. Four distinct types of GluN2 subunits (GluN2A‐D) are known and impart divergent receptor properties including changes in agonist affinity and channel gating. In the present study, we identified a sequence of amino acids in the pre‐TM4 region of GluN2B that affects ligand affinity and the effectiveness of ethanol to inhibit the channel. This sequence, that immediately precedes the fourth transmembrane domain, is highly conserved amongst GluN2 subunits. Glycine substitutions at discrete locations within this sequence produce a significant leftward shift of the glutamate concentration‐response curve and currents display a significantly longer decay constant. Furthermore, glycine substitutions in this region also increase the sensitivity of the receptor to ethanol inhibition. Ongoing studies are focused on determining how this region, distinct from the S1 and S2 ligand‐binding domain, affects the sensitivity of the receptor to agonists and antagonists.Supported by grants T32 AA007474 (B.A.H) and R37 AA009986 (J.J.W.).
Relating mood to plasma glutathione and BDNF levels in patients with bipolar disorder
Authors: Singh Nisha , Rosa Adriane R , Whitaker Eleanor , de Britto Marianne , Lewis Alexander , Vieta Edward , Churchill Grant C , Geddes John R , Goodwin Guy M 
Published: June 2021

ObjectiveTo correlate self‐reported mood scores (depression and mania) with plasma levels of brain derived neurotrophic factor (BDNF) and glutathione in medicated bipolar patients.MethodsBDNF (ELISA) and glutathione levels (enzymatic recycling, Ellman's reagent) were measured in plasma from 50 bipolar patients and matched healthy controls. The True Colours database (OXTEXT, University of Oxford) was used to determine mood‐monitoring scores for the bipolar group with the Quick Inventory of Depressive Symptomatology (QIDS) and the Altman Self‐Rating Mania Scale over an 8‐week period.ResultsBipolar patients had significantly lower levels of reduced glutathione and higher levels of oxidized glutathione, while BDNF levels were not significantly different. 22% and 64% of the patients had scores ≥ 6 on the Altman scale and QIDS, respectively, but mood state did not correlate with antioxidant level.DiscussionThe results suggest that, despite medication, bipolar patients show higher levels of oxidative stress and that the majority still have depressive symptoms. The direction of effect is not established, but these observations appear to be consistent with studies that suggest N‐acetyl cysteine, an antioxidant, reduces depressive symptoms in bipolar patients. Hence, combining an antioxidant with other mood‐stabilizers may be therapeutically beneficial in the treatment of bipolar disorder.
Tepary bean lectins induces apoptosis on human colon cancer cells and inhibits early tumorogenesis in rats
Authors: Garcia‐Gasca Teresa , Ferriz‐Martinez Roberto , Cervantes‐Jimenez Ricardo , Angeles‐Zaragoza Marco Vinicio , Andrade‐Portillo Veronica , Blanco‐Labra Alejandro , Rodriguez‐Mendez Adriana Jheny , Gallegos‐Corona Marco Alonso , Lopez‐Martinez Francisco Josue , Mendiola‐Olaya Elizabeth 
Published: June 2021

The aim of this study was to determine whether a lectin fraction (LF) from Tepary bean seeds (Phaseolus acutifolius) exhibits apoptotic induction on colon cancer cells and its in vivo effect on tumorogenesis in rats. Median lethal concentration (0.402 mg protein/mL) on HT‐29 cells caused a significant increase in caspase 3 activity, an overexpression of caspase 3 (35%) and caspase 9 (78%) and a 36.6% apoptosis increase determined by flow cytometry. Colon cancer was induced on male Sprague Dawley rats treated for 8 weeks with 1,2‐dimethylhydrazine (DMH) (40 mg/body weight kg) and a subsequent administration of 50 mg of LF/body weight kg for 6 weeks. The LF provoked a decrease in food consumption and body weight of rats with a partial recovery at the end of the experiment. Histopathological analysis showed that LF decreased the incidence of early stages tumors in a 53% but no effect was observed on high grade carcinogenesis. The results show that LF induces apoptosis in colon cancer and it has inhibitory effect on early tumorogenesis.Founding: CONACYT Ciencia Básica (82349)
Doxycycline does not reverse structural observed in SHR aortas
Authors: Gerlach Raquel F , Antonio Raquel Carros , Ceron Carla S , Rizzi Elen , Coelho Eduardo B , dos Santos Jose Eduardo Tanus 
Published: June 2021

This study aimed at testing whether doxycycline (dox) would change the vascular structure, gelatinolytic activity and MMP‐2 levels in SHR aortas of 13‐week‐old animals treated for 5 weeks. SHR and Wistar‐Kyoto controls received either dox 30 mg/kg/day by gavage or vehicle. Systolic blood pressure (SBP) was assessed weekly by tail cuff, and at the end the aortas were processed for histological analysis and in situ zymography. Histological sections were used to determine media cross‐sectional area (CSA), media/lumen diameter (M/L), and the number of smooth muscle cells (SMC). Gelatinolytic activity was measured in situ using DQ gelatin. SBP was significantly lower in the SHR + doxy group compared to the SHR vehicle (P< 0.05). No changes were seen in any of the structural parameters (p>;0.05). Gelatinolytic activity was 3 times higher in the SHR aortic media (53.4 ± 15 units) compared with Wkyoto controls (18.2 to 18.9 ± 6 units), and dox treatment decreased the SHR values to 26.0 ±8 units (P <0.0001). Data confirms the high expression and activity of MMP‐2 in aortas of SHRs, and the effect of doxycycline in reversing the increase in SBP. However, at least for the time frame used (5 weeks) these changes were not concurrent with structural changes in the aortas, as shown in other models of hypertension after dox treatment.Support: State of Sao Paulo Research Foundation (FAPESP) and National (Brazilian) Research Council (CNPq).
Aging augments apoptosis of endothelial cells in mice
Authors: Campagnaro Bianca Prandi , Tonini Clarissa Loureiro , Porto Marcella Leite , Vasquez Elisardo Corral , Meyrelles Silvana Santos 
Published: June 2021

We evaluate mice endothelial cells (EC) apoptosis in aging and atherosclerosis by flow cytometry.Male apolipoprotein E‐deficient (ApoE, N=10) mice were separated in two groups according to their ages: 2 and 18 months old and compared with C57BL/6 mice (C57, N=10). Animals were euthanized and EC mechanically isolated from aorta. For apoptosis analysis, 105 cells were incubated with Annexin V‐FITC and propidium iodide (PI) at room temperature during 15min. Events were acquired by FACSCanto II and analyzed by FACSDiva software. Data are means±SEM. p<0.05 (two‐way ANOVA).Flow cytometric analysis showed that atherosclerosis did not affected EC apoptosis between young (C57: 1.9±0.2 vs. ApoE: 1.15±0.12 %) and aged (C57: 23.25±7.7 vs. ApoE: 23.36±0.55 %) groups. However, aging augments apoptosis of EC in ApoE (Young: 1.15±0.12 vs. Aged: 23.36±0.55 %) and C57 (Young: 1.9±0.17 vs. Aged: 23.25±7.71 %) groups.Our data showed that atherosclerosis per se was not able to induce apoptosis. However, aging was directly responsible for augmentation of EC apoptosis.
Evidence that chronic inhibition of the mammalian Target of Rapamycin (mTOR) reduces skin blood flow in humans
Authors: Kellogg Dean Lundt , Zhao Joan , Wu Yubo , Roman Linda , Johnson John Marshall 
Published: June 2021

Chronic mTOR inhibition causes vascular dysfunction in rodents. We hypothesized that a similar effect would be observed in humans. 6 middle‐aged persons participated. mTOR was antagonized by topical application of 8% rapamycin (RAPA) ointment to skin. RAPA was applied twice daily for 7 days to an 8×8 cm area of skin on the abdomen while a second site was similarly treated with ointment vehicle only. We examined the effect of these treatments on skin blood flow (SkBF) as monitored by laser‐Doppler flowmetry (LDF). Local skin temperature (Tloc) was controlled with combined LDF/local heating probe holders. Tloc was maintained initially at 34°C and then was raised to 43°C to cause maximal local vasodilation (maxLDF).ResultsAt Tloc=34°C, SkBF was 72±4.3% maxLDF at RAPA treated sites and was 80±4.9% maxLDF at sites that received vehicle only (p<0.03 between sites). maxLDF (in mV) when Tloc was 43°C did not differ between RAPA and vehicle treated sites (p>;0.05). We conclude that chronic RAPA treatment reduces SkBF levels at normothermic skin temperatures in middle‐aged persons without an effect on maximal vasodilation. (supported by NIH Grant AG041365)
Voluntary exercise at young stage prevents glucose intolerance in type 2 diabetic rats
Authors: Tsuzuki Takamasa , Yoshihara Toshinori , Ichinoseki‐Sekine Noriko , Kobayashi Hiroyuki , Naito Hisashi 
Published: June 2021

PurposeTo investigate the effects of voluntary exercise at young stage on whole‐body metabolism and glucose tolerance in type 2 diabetic rats.MethodsOtsuka Long‐Evans Tokushima Fatty (OLETF) rats as an animal model of type 2 diabetes and their counterparts (Long‐Evans Tokushima Otsuka; LETO) were used. Twenty male OLETF and LETO rats were divided into three groups, respectively: Sedentary (SED, n=8), Wheel Running (WR, n=6), or Wheel Running‐Sedentary (WS, n=6) group. WR and WS groups were allowed to access a running wheel freely from 5 to 25 week‐old. In WS group, however, a running wheel was locked from 15 to 25 week‐old and rats could not run in the wheel. At 25 week‐old, resting oxygen consumption (VO2 rest) of each rat was measured in a metabolic chamber. Subsequently an intraperitoneal glucose tolerance test (IPGTT) was performed.ResultsThere were no significant differences in the areas under the curve of IPGTT (AUC) and VO2 rest (ml/kg/min) among three LETO groups. In OLETF rats, AUC in WR and WS groups were significantly lower than SED group, with AUC being lower for WR group. Moreover, VO2 rest of OLETF in WR and WS groups were significantly higher than SED group.ConclusionOur data suggest that voluntary exercise at young stage improves resting metabolism and prevents glucose intolerance in grown‐up type 2 diabetic rats, and these effects remained following exercise cessation.
Epigenetic regulation of LPS‐induced lung injury by sphingosine‐1‐phosphate lyase (1001.10)
Authors: Ebenezer David , Zhao Yutong , Ackerman Steven , Natarajan Viswanathan 
Published: June 2021

Sphingosine‐1‐Phosphate Lyase (SGPL1) irreversibly hydrolyses Sphingosine‐1‐Phosphate (S1P) to ethanolamine phosphate and hexadecenal in mammalian cells. We have earlier demonstrated that inhibition or down‐regulation of Sphingose‐1‐Phosphate Lyase (SGPL1) ameliorates lipopolysaccharide (LPS)‐induced lung inflammation in mice. Therefore, challenge causes lung injury by increasing Sphingosine‐1‐Phosphate Lyase (SGPL1) expression, and inhibition of SGPL1 activity could produce therapeutic levels of immunosuppression. Our study is aimed to define SGPL1 mediated epigenetic regulation of LPS‐induced inflammatory responses in lung endothelium. Our preliminary data showed that down regulation of S1PL with siRNA blocked LPS‐induced IL‐6 secretion and partially blocked LPS‐induced acetylation of Histone H3 and Histone H4. Also, knock down of SGPL1 decreased MYST2 and IL‐6 promoter activity and potentiated Histone Deacetylase (HDAC) 5 expression. Moreover, Blocking HDAC activity with Trischostatin A potentiated LPS‐induced IL‐6 secretion while Histone Acetyl transferase (HAT) inhibitor Anacardic acid attenuated IL‐6 production. Taken together, these data reveal a potential epigenetic regulation mediated by SGPL1 in LPS‐induced lung inflammation.Grant Funding Source: Supported by National Institute of health P01HL098050
Steroids contents of wound healing preparations from the skin of the Arabian Gulf catfish (Arius bilineatus, Val.) (1001.7)
Authors: Al‐Hassan Jassim , George Sosamma , Afzal Mohammad 
Published: June 2021

The Arabian Gulf catfish secretes copious amounts of epidermal gel‐like material when threatened or injured. The freeze dried gel contained 85% proteins, 14.4% lipids 2.6% nucleic acid components and carbohydrates.Preparations from the skin of the catfish were found to accelerate the rate of wound healing, as well as being potent anti‐inflammatory. The lipids were composed of non‐polar lipids, glycolipids and phospholipids. Analysis of the lipids for steroids using TLC, FTIR, 1HNMR, 13CNMR, GC/MS, and GC/MS/MS showed them to contain 14 steroids, including 12 oxysterols. The following compounds were characterized: cholesterol, 7α‐hydroxy cholesterol, 7β‐hydroxycholesterol, 5,6 epoxycholesterol, 3β‐hydroxycholest‐5‐ene‐7‐one, cholest‐3,5‐diene and cholesta‐3,5‐dien‐7‐one. Progesterone, cholest‐3,5,6‐triol and 4‐cholesten‐3‐one were found as minor components, and were identified by comparing their MS, 1HNMR and FTIR spectral data with those of standards and library data. Cholest‐3,6‐dione, cholesta‐4,6‐diene‐3‐one, cholesta‐2,4‐diene, and cholesta‐5,20(22)‐dien‐3‐ol were found only in trace amounts and were identified by GC/MS and MS and their spectral data were compared with library data. The bile of the catfish was found to contain 6 bile acids and salts. The presence of the oxysteroids together with eicosanoids, platelet activating factors, furan fatty acids and unsaturated fatty acids in the skin secretion may help understand the pharmacological and therapeutic activities of the preparations from the skin of the catfish.Grant Funding Source: This project is supported by Research Administration, Kuwait University Grant No. SL04/09
The hypertriglyceridemic waist, waist‐to‐height ratios and cardiometabolic risk in university students (1001.8)
Authors: Villalobos Raffael D , Villalobos Daniel , Murguía‐Romero Miguel , Jiménez‐Flores Raffael , Méndez‐Cruz René , Sigrist‐Flores Santiago , Medrano Gabriel , Villalobos‐Molina Rafael 
Published: June 2021

We used hypertriglyceridemic waist (HW) and waist‐to‐height ratios (WHTR) as simple clinical approaches to identify young adults at risk of cardiometabolic disorders. This cross‐sectional design study was assessed in 4619 students (3142 women) aged 17‐24 years from first grade university, México. Body mass index (BMI), waist circumference (WC) and biochemical variables were determined. The HW phenotype was defined as a waist circumference > 90th percentile for age and sex, and triglyceride concentrations > 1.24 mM, and a high WHTR was defined as > 0.5. We found 42.2% students with increased WC, 18% hypertriglyceridemic and 11.6% of HW phenotype among the sample. Waist circumference and the HW phenotype seem to predict better those young adults at increased risk for cardiometabolic disorders, i.e., those who bear components of metabolic syndrome/insulin resistance.Grant Funding Source: RV‐M is supported by PASPA, DGAPA, UNAM
Human dendritic cells induce B‐cell responses to polysaccharide antigens (1004.2)
Authors: Mendoza Daniel , Xu Yi , Rodriguez‐Barradas Maria , Tweardy David , Orson Frank , Corry David 
Published: June 2021

Background: Carbohydrates mediate host‐pathogen interactions and play prominent roles in cancer and inflammatory diseases. The large majority of carbohydrates directly activate B cells without T cell help to produce antibody responses. For a long time, these responses were assumed to be independent of antigen‐presenting cells (APC). However, recent studies in mice indicate a role of APC in T‐cell independent responses. To determine whether human APC play a role in immune responses to carbohydrates, we characterized dendritic cell (DC) responses to pneumococcal polysaccharides (PS) and PS‐based vaccines (PCV13 and PPV23).Methods: we incubated human monocyte‐derived DC (MDDC) with a fluorochrome‐labeled PS at various time points to measure antigen internalization in DC by deconvolution microscopy. In different experiments, we exposed PBMC of unvaccinated healthy donors to PS‐based vaccines for 6 hours ex vivo to measure IL‐8 production in DC by flow cytometry. Finally, we incubated human B cells with PS with and without autologous MDDC to measure IgG production by ELISA 6 days later.Results: Human DC internalized PS within 1 hour of exposure. IL‐8 was the main cytokine produced in PBMC in response to PS. Percent of DC producing IL‐8 in response to PS‐based vaccines were: medium: 5.15%, PCV13: 23%, PPV23 10%, (p<0.0001). DC induced IgG responses to PS: B cells alone: 33.3; B cells+PS: 25.5; DC+B cell alone: 60.2; DC+B cell+PS: 114 ug/ml, p=0.04. DC induced IgM production to PS as well.Conclusions: human DC interact with PS and induce B‐cell responses to PS. Overall, we have identified a novel and essential immune role for human DC in immune responses to carbohydrate antigens with important implications for vaccine design and immunogenicity.
Angiotensin‐II‐induced expression of the early growth response protein 1 is mediated by CaMKII‐dependent pathway in vascular smooth muscle cells (1011.7)
Authors: Simo Cheyou Estelle , Srivastava Ashok 
Published: June 2021

Egr‐1 is a transcription factor implicated in the regulation of several growth‐related cascades. It has been suggested to participate in the development of vascular disease processes such as intimal thickening following vascular injury, atherosclerosis and cardiac hypertrophy. Upregulation of Egr‐1 was recently shown to be a key contributing factor in stimuli‐induced VSMC proliferation and hypertrophy. Ang‐II, a potent vasoactive peptide with pathogenic role in vascular disease, has been demonstrated to contribute to aberrant remodeling of the vessel wall. This is mainly due to the ability of Ang‐II to activate hypertrophic and proliferative pathways such as the mitogen‐activated protein kinase and the phosphatidylinositol‐3‐kinase pathways in VSMC. It has been shown earlier that Ang‐II requires H2O2 generation to activate these signaling pathways and we have shown that Ca2+, calmodulin (CaM) and Ca2+/CaM‐dependent protein kinase II(CaMKII), play a critical role to trigger H2O2‐induced effects in VSMC. We have also shown that endothelin‐1, another mitogenic vasoactive peptide, requires CaMKII to upregulate Egr‐1 expression and to mediate its physiological responses. However, Ang‐II‐induced modulation of Egr‐1 expression in VSMC and the implication of CaMKII in this process remain unexplored. Therefore these studies were undertaken to characterize the effect of Ang‐II on Egr‐1 expression in A10 VSMC and to examine the role of Ca2+, CaM and CaMKII on this response. Ang‐II, at 100nM, induced an increase in Egr‐1 expression in a time‐dependent fashion in the nucleus of A10 VSMC. Pharmacological blockade of CaM and CaMKII by calmidazolium and KN‐93 respectively, significantly attenuated Ang‐II‐induced Egr‐1 expression. These results demonstrate that Egr‐1 expression is upregulated in response to Ang‐II via CaM/CaMKII‐dependent pathways in VSMC.Grant Funding Source: Supported by the Canadian Institutes of Health Research