bluuebunny/crossref_metadata_2025_split huggingface dataset:
CAIDE Dementia Risk Score Indicates Cortical Thinning in Low‐Risk, Middle‐Aged Adults
Authors: Gourley Drew , Pasha Evan P. , Kaur Sonya S. , Haley Andreana P. , Tanaka Hirofumi 
Published: June 2021

Increased risk for the future development of Alzheimer's disease begins as early as midlife and can be predicted using modifiable cardiovascular and lifestyle‐related risk factors. The Cardiovascular Risk Factors, Aging and Incidence of Dementia (CAIDE) dementia risk score has been used to predict late life risk of dementia based on midlife vascular risk factors. Additionally, in older adults with mild or subjective cognitive impairment, higher CAIDE scores were associated with greater atrophy in the middle temporal and frontal regions of the brain.PurposeWe aimed to determine if CAIDE score is associated with cortical thickness in middle‐aged cognitively intact adults at risk for cardiovascular disease. We hypothesized individuals with higher CAIDE scores would have reduced cortical thickness in a priori regions associated with memory and attention‐executive function.MethodsA total of 155 middle‐age adults (49±6 years, 52.4% female) classified as cognitively normal were studied. CAIDE score was calculated using the original model that excludes ApoE e4 genotype. This includes age, sex, education level, systolic blood pressure, body mass index, total cholesterol, and physical inactivity. Each factor is given a specific weight and the total score ranges from 0 to 14. Cortical thickness was obtained from high resolution magnetization‐prepared rapid acquisition gradient‐echo images. Thickness values for 24 a priori regions of interest associated with memory and executive function were extracted and analyzed.ResultsA majority of the participants (95.5%) in this sample were categorized as low‐risk, having a CAIDE score of 8 or lower. After using a corrected p‐value (p=0.006) for multiple correlations, there were several significant negative associations between CAIDE score and cortical thickness. These include the right parahippocampal (r=−0.251, p=0.002), left pars opercularis (r=−0.244, p=0.002), right superior frontal (r=−0.229, p=0.004) and left superior frontal (r=−0.247, p=0.002) regions.ConclusionsHigher CAIDE scores in midlife are associated with lower cortical thickness in middle‐age adults at risk for cardiovascular disease. This finding supports the notion that cardiovascular risks may contribute to early alteration of brain structure. We propose that the CAIDE dementia risk score may be useful in predicting future risk of dementia even in low‐risk populations who have no indication of clinically significant cognitive impairment.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Free Radical Scavenging Activities of Extracts and Bioactive Constituents from the Roots of Plumbago zeylanica (Linn.)
Authors: Ajayi Gabriel Olukayode , Ademuyiwa Oladipo , Olagunju Joseph Abayomi , Lasisi Aliyu 
Published: June 2021

Bioactive constituents from the methanolic extract (ME) and ethylacetate extract (EA) of Plumbago zeylanica were characterized by gas chromatography‐mass spectrometry. The free radical scavenging activities of ME and EA was determined using 1,1‐diphenyl‐2‐picryl‐hydrazyl (DPPH). Major bioactive compounds found in the ME includes oxalic acid allyltridecyl ester, decane, 2‐piperidinone‐N‐[4‐bromo‐n‐butyl] and tetradecane, compounds obtained from EA were 1‐(ethenyloxyl) octadecane and cis‐13‐octadecenoic acid. Cis‐13‐octadecenoic acid, though known, was isolated for the first time from the root of P. zeylanica. The highest percentage antioxidant activities of ME and EA were 98.5% and 45.5% respectively at 350 μg/ml concentration of extracts. Results obtained from this study justify the use of P. zeylanica in traditional medicine for treatment of different ailments and it could be a potential source for novel drug compounds.Support or Funding InformationContributions from authorsThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Wound healing property of aerial parts of Coleus vettiveroides
Authors: Ponnan Jeyasekhar M , Edward Jaslin J , Johnson Rajasingh K 
Published: June 2021

BackgroundColeus vettiveroides is a Labiatae species native to India. In Kenya, the leaves of some species within this genus having diterpenes, triterpenes and flavones compounds were used traditionally for treating the cough. However, to our knowledge, there is no experimental study in supporting its pharmacological activities.HypothesisWe hypothesize that topical administration of ethanolic extracts from the leaves of C. vettiveroides enhances wound healing in rat model.Methods and ResultsFour groups of male albino rats were selected (n=6) in this study. Full thickness of excisional circular wounds approximately 10 mm diameter were inflicted on the clear skin cutting under anesthesia. A diagrammatic representation of the murine wound‐healing model is presented in the figure. The ointment developed namely ethanolic extract of C. vettiveroides (EEVS) 2.5 mg/g and 5 mg/g was applied twice a day topically to 2nd and 3rd group respectively for 15 days. Whereas, the 1st group applied with simple ointment serve as negative control and the 4th group applied with silver sulfadiazine (10 mg/gm) topically serves as positive control. Wound contraction was measured on day 2, 4, 6, 8,12,14 and 15. The measurements were compared to the control groups. On day 15, the wounds treated with the EEVS show a significantly reduced wound size and a better wound healing effect both physiologically and histologically when comparted to the control groups. These results suggest that EEVS ointment has the wound healing potential.ConclusionOverall, these data suggest that the ethanolic extract from leaves of C. vettiveroides has the wound healing activity. Thus, these plant extracts have a therapeutic application.
imageThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
ENaC Activity and Regulation in Renal Distal Convoluted Tubule Cells
Authors: Song Chang , Le Janet , Yue Qiang , Mistry Monisha , Wynne Brandi , Ma Heping , Eaton Douglas C. 
Published: June 2021

Our previous work has shown that epithelial sodium channel (ENaC) proteins are present in distal convoluted tubule (DCT) cells of the distal nephron. The purpose of these experiments was to show whether these proteins were functional. We also wish to show whether the channels were stimulated by aldosterone, inhibited by amiloride, and regulated by the ENaC chaperone protein, MLP‐1, as ENaC is regulated in collecting duct principal cells. We used DCT‐15 cells in monolayer culture on permeable polyester supports to measure transepithelial voltage, resistance, and current. The properties of DCT‐15 cells are quite similar to those of in situ cells of the DCT2 segment of the nephron. Our results showed that DCT‐15 cells had relatively low resistances (206 ± 5.71 Ω‐cm2, n=36) and small, but measurable amiloride‐sensitive currents (2.87 ± 0.237 μA, n=36), showing that these cells contain functional ENaC. 100 nM aldosterone significantly increased mean DCT‐15 cell current (from 2.87 ± 0.237, n=36, to 5.33 ± 0.395μA, n=8). Amiloride significantly lowered the current across DCT cells to very low levels (from 2.74 ± 0.219, n=42, to 0.825 ± 0.186μA, n=15). MLP‐1 is a myristoylated protein that when associated with the membrane promotes ENaC activity. When three critical serines are phosphorylated by PKC, MLP‐1 dissociates from the membrane and ENaC activity decreases. We transfected the cells with four MLP FLAG‐tagged mutants: wild type (WT), constitutively active (S3A), constitutively inactive (S3D), and myristoylation negative (GA) and measured DCT‐15 current. For comparison, we examined a principal cell line, mpkCCD cells. Transfection with MLP‐1 modified current in both DCT and CCD cells: median current was highest in S3A mutant and lowest in S3D mutant; the current after transfection with either construct was significantly different from WT. ENaC and MLP construct expression was also studied in lysates of both cell types by Western blotting with FLAG and anti‐ENaC subunit antibodies. In DCT‐15 cells with the highest current, expression of ENaC was greatest. Lastly, we calculated based on an average current of 2 μA/cm2 and ENaC single channel current of 0.4 pA that DCT‐15 cells must have approximately 5 million functional channels per square centimeter.Support or Funding InformationSupported by R01 DK‐110409 to DCE and K01 DK‐115660 and ASN Gottschalk AWARD to BMWThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Comparison of Alpha‐2‐Macroglobulins from Swine and Humans and their Copper Binding
Authors: Garcia Alejandra , Ramos Danny , Marzvaan Cameron , Vileno Bertrand , Faller Peter , Linder Maria C 
Published: June 2021

Alpha‐2‐macroglobulin (a2M) is a member of the macroglobulin family of blood plasma proteins. It has a variety of functions, ranging from trapping proteases and transporting zinc to binding and transporting inflammatory and anti‐inflammatory cytokines and, growth factors and the small peptide regulating iron metabolism (hepcidin)[1]. a2M is the main form found in most mammals, while the alpha1‐inhibitor3 form dominates in the plasma of rodents. Some years ago, we determined in rats that a large plasma protein we named transcuprein was involved in transporting copper to the liver (exchanging copper with albumin), and upon purification found it was alpha1‐inhibitor3[2]. We then showed that human a2M also bound Cu(II) tightly, and that this copper was readily delivered by a2M to cultured human cells[3]. As we have been studying aspects of copper metabolism in pigs, we decided to also investigate the structure and copper binding of pig a2M to compare it to that of human a2M. Pig and human a2M were purified from heparinized Yorkshire pig plasma and from the heparinized plasma of human volunteers (under an approved university IRB protocol), using the established procedure for human a2M that uses a combination of PEG 8000 fractionation and Zn(II)‐immobilized metal affinity chromatography. The resulting samples were separated in large pore size exclusion chromatography on Sephacryl S300. Human a2M eluted had one large peak eluting with an Mr of ~900 kDa, and a much smaller peak of about 400 kDa. By SDS‐PAGE, both peaks showed the expected 180 kDa band, indicating that most of the human a2M was a tetramer, with a very small portion as a dimer. In the case of the pig, There was not tetrameric a2M; it was all in dimer form, and the subunits seen in SDS‐PAGE were two bands that together added up to ~180 kDa (120 + 60 kDa). Non‐denaturing PAGE gave single bands indicating that the smaller subunits of the pig a2M were combining into one structure. The copper content of the human a2M was 4 Cu atoms per tetramer (not taking into account potential non‐specific binding), but was 2 Cu atoms per tetramer when copper was first removed and added back in the presence of human or rat albumin. The Cu content of the pig a2M was 4 Cu atoms per dimer. Preliminary data obtained by EPR gave similar but not identical profiles and indicated there were two binding sites, the main one with Cu(II) atoms most likely bound to three Ns and one O. These findings indicate that in some species, a2M forms a dimer, while in others a tetramer; they bind Cu(II) in similar but not identical fashion; and that the subunits of pig a2M may have a vulnerable peptide bond that cleaves the 180 kDa unit into two pieces.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Renal Expression of Adhesion GPCR Gpr116 (ADGRF5) Contributes to Urinary Concentration in Mice
Authors: Zaidman Nathan , Pluznick Jennifer 
Published: June 2021

G‐protein coupled receptors (GPCR) are a large and diverse family of integral membrane proteins that recognize a tremendous assortment of extracellular molecules including neurotransmitters, hormones, light and odors. They are a common target of pharmaceutical drug development, and uncovering the function of novel GPCRs in the kidney represents a wealth of untapped therapeutic potential. We previously performed an mRNA screen for novel GPCRs in the kidney to identify promising yet overlooked renal GPCRs. This screen revealed that Gpr116, an adhesion‐class GPCR, is highly expressed in the kidney. To understand the role of Gpr116 in renal physiology, we have taken a multidisciplinary approach. Using transfected HEK293 cells expressing cloned Gpr116, we validated a monoclonal antibody for Gpr116. In murine kidney, this antibody localizes Gpr116 to the apical membrane of intercalated cells in the collecting duct of mouse kidneys. This staining is absent in kidneys from targeted knockout (KO) of Gpr116 in renal tubules (Gpr116flox/flox, ksp‐Cre). Additionally, kidney‐specific KO animals have significantly reduced spot urine osmolality (1552±71 mOsm/kg, N=11) compared to wild‐type (WT) (2097±76, N=10, p<0.0001) and heterozygous (2423±86, N=6, p<0.0001) littermates. Furthermore, following 24‐hours of dehydration plasma vasopressin is not significantly upregulated from baseline in KO animals, but is in WT littermates. However, osmolality of 24‐hour urine collections from metabolic cages are not significantly different between the WT and KO groups. Overall, these results suggest a role for Gpr116 in the urinary concentrating mechanisms in the murine kidney. This study establishes a physiologic role of the previously understudied Gpr116 in the murine kidney and demonstrates the scientific potential of future investigations into novel GPCRs.Support or Funding InformationResearch was funded by NIH F32DK116499 (N.A.Z.) and NIH R01DK107726 (J.L.P.).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Advanced Stages of Duchenne Muscular Dystrophy Exhibit Mitochondrial Bioenergetic Impairments Linked Specifically to Creatine‐Dependent Energy Exchange
Authors: Hughes Meghan C , Ramos Sofhia V , Turnbull Patrick C , Perry Christopher G R 
Published: June 2021

RationaleOur recent findings demonstrate that left ventricle and diaphragm from 4 week old D2.mdx mice with Duchenne Muscular Dystrophy (DMD) exhibit impaired mitochondrial oxidative phosphorylation and elevated H2O2 (mH2O2) emission. The present investigation sought to determine the degree of these deficits in advanced stages of DMD.MethodsADP‐dependent mH2O2 emission and respiration were assessed in permeabilized muscle fibre bundles from heart and diaphragm muscle of D2.mdx mice (52 weeks). Mitochondrial assessments were performed in the presence of 20mM creatine (+Cr) to maximally activate mitochondrial creatine kinase (mtCK)‐dependent shuttling of phosphate to the cytoplasm as phosphocreatine, which accelerates matrix ADP/ATP cycling, as well as in the absence of creatine (−Cr) to force mitochondria to rely solely on slower ATP/ADP diffusion.ResultsState II mH2O2 emission (0 mM ADP, maximal mH2O2 emission) was unchanged in DMD heart and lower in DMD diaphragm in both +Cr (96.0 pmol/sec/mg dry wt in DMD vs 498.0 pmol/sec/mg dry wt in WT, p<0.05) and –Cr (50.2 vs 312.9, p<0.05). 25 mM ADP was added to evaluate the ability of ADP to lower mH2O2 emission (state III). ADP's ability to lower mH2O2 emission was impaired in +Cr (heart: 69% of state II mH2O2 in DMD vs 61% in WT, p=0.06; diaphragm: 75% vs 54%, p<0.05) but improved in −Cr in the heart (69% vs 98%, p<0.05), and unchanged in diaphragm. State III respiration was also evaluated using 25 mM ADP. +Cr, respiration was impaired in the heart (48.0 pmol/sec/mg wet wt in DMD vs 75.6 pmol/sec/mg wet wt in WT, p<0.05) and diaphragm (43.4 vs 47.8, p<0.05). −Cr, respiration was improved in DMD heart (60.0 vs 29.8 pmol/sec/mg wet wt, p<0.05) and unchanged in diaphragm. The greater mH2O2 due to impaired mtCK did not alter heart glutathione in reduced or oxidized forms, total glutathione or GSH/GSSG, but did increase diaphragm glutathione in oxidized, reduced and total forms (117–204%, p<0.001).ConclusionThese findings demonstrate that mitochondrial dysfunctions during advanced stages in DMD are attributed specifically to an impaired ability of creatine to enhance ADP's control of respiration and mH2O2 emission. A partial compensation in creatine‐independent control of ADP was observed which may prevent even further detriments to cellular energy and redox homeostasis. These findings suggest that restoration of normal mtCK activity and mitochondrial creatine‐dependent phosphate shuttling may be an effective approach at restoring mitochondrial bioenergetics and countering muscle‐specific weakness in DMD.Support or Funding InformationNSERC Discovery Grant, The James H. Cummings Foundation, Canadian Foundation for Innovation, Ontario Research FundThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Allicin Reverses Diabetes‐Induced Dysfunction of Human Coronary Artery Endothelial Cells
Authors: Horuzsko Daniel , LaCavera Margeaux , Ma Handong , Wu Yan , Zhu Shu , White Richard 
Published: June 2021

Cardiovascular disease (CVD) is the leading cause of death in the United States, and is the major source of morbidity and mortality associated with diabetes mellitus. Because the incidence of diabetes continues to increase, reducing the risk of CVD in diabetes will continue to be a major focus of cardiovascular research. An early manifestation of diabetes‐induced CVD is dysfunction of the vascular endothelium, as indicated by depressed production of NO. Our findings now demonstrate depressed activity of endothelial nitric oxide synthase (eNOS) in diabetes, and suggest that treating human coronary artery endothelial cells with allicin, the major bioactive organosulfur component in garlic extract, can restore NO production in these cells. Coronary artery endothelial cells (Lonza) were obtained from control (HCAEC) or diabetic (DHCAEC) donors, and NO production was measured by fluorescence microscopy via 4,5‐diaminofluorescein diacetate. On average, NO production was depressed by 12.9% in DHCAEC compared to controls. Treating these cells for 20 minutes with 4 μM allicin restored NO production by 32.9%. Further, immunoblot studies revealed that diabetes decreased expression of eNOS protein by 20.3%; however, allicin was able to reverse this effect of diabetes. On average, eNOS expression was increased by 26% by overnight exposure to 5 μM allicin. Taken together, these data indicate that allicin improves endothelium‐dependent NO production in diabetes by enhancing the expression and/or activity of eNOS in human coronary artery endothelial cells. These studies further suggest that this improved endothelial function likely contributes to the established health benefits of garlic consumption (e.g., lowering blood pressure), and also suggests a natural means of reducing the devastating consequences of diabetes on CVD. Future experiments are needed to identify the mechanism of allicin action on eNOS and in vascular endothelial cells.Support or Funding InformationSupported by the Division of Research, PCOM.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Anticancer mechanisms determination of N‐(o‐carboxybenzoyl)‐derived compounds of L‐amino acids serie on MDA‐MB‐231 cell line of TNBC
Authors: MARTINEZ DORIS CRUZ , PERCINO TERESA MANCILLA , JIMÉNEZ ELVIA MERA 
Published: June 2021

Breast cancer is ranked as the second most frequent neoplasm worldwide [1], of which approximately 15% is subclassified as triple negative breast cancer (TNBC), characterized by absence of estrogen, progesterone and HER2/neu receptors. TNBC has been identified as one of the most aggressive cancers, due to its null response to endocrine therapies and trastuzumab [2]. Breast cancer is a pathology associated with aging and unhealthy lifestyles, which has been proven through studies that demonstrate MDA‐MB‐231 TNBC cells overexpress HDAC8 as a consequence of epigenetic dysregulation mechanisms linked to the high level proliferative capacity, resulting into high risk of recurrence and low survival [3]. Because all above our work group has focused in the design by Docking technique and synthesis of new HDAC inhibitor (HDACi) compounds as a therapeutic target for the TNBC. In this investigation, N‐(o‐carboxybenzoyl) derived compounds of L‐amino acids were used to determine their cytotoxicity by inhibiting the proliferation and viability of the cell line MDA‐MB‐231, as well as elucidate the possible mechanisms of cell death induced by the compounds BisLys, GlutEt and I1.MethodsTo evaluate overall cellular toxicity of BisLys, GlutEt and I1 compounds, MDA‐MB‐231 cells were seeded and incubated at 37°C in a 5% CO2, DMEM F12 medium supplemented with FBS. Compounds were added in 8 different concentrations, DMEM F12 medium was used as a negative control and SAHA as a positive control. The proliferation and viability of TNBC cells was quantified by the colorimetric for 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay. Type of cell death whether it was necrosis or apoptosis was determined using Annexine V and propidium iodide by flow cytometry. Finally, the blocked cell cycle progression by those compounds was determined using Cayman 10009349 Kit by flow cytometry.ResultsThe compounds BisLys and Glut Et decreased cell proliferation via apoptosis after 24h of treatment and blocked cell cycle progression at G1 phase with a concurrent decrease in S and G2/M phase. On the other hand, compound I1 did not significantly decrease cell proliferation after 24 hours of treatment. However, it shared the blocked cell cycle progression at G1 phase in the same way as the BisLys and Glut Et compounds.ConclusionCompounds BisLys and Glut Et were able to inhibit the proliferation of the MDA‐MB‐231 cell line and induced blocked cell cycle and cell death mainly by apoptosis, so they could be considered as potentially therapeutic compounds.Support or Funding InformationThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.