bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activation of SirT1 and NAMPT preserves late‐in‐life fertility of female Nothobranchius guentheri.
Authors: Shay Kate Petersen , Thomas Nicholas O. , Lee Youngjoo , Drake Andrew C. , Ferguson Lindsey G. , Chappell Patrick 
Published: June 2021

The decline of female reproductive function is an early phenotype of aging, occurring only midway through the lifespan. Yet, women's ability to delay pregnancy and preserve fertility is an important reproductive freedom. The number of women delaying pregnancy continues to rise in industrialized societies due to personal or socioeconomic circumstances, often resulting in subfertility or difficulty conceiving. There are few defined mechanisms associated with this etiology, and equally few effective therapies. To combat this problem, we used a novel emerging model, Nothobranchius guentheri, with a lifespan of only 9–12 months, that recapitulates the age‐associated spectrum of changes that adversely affect human fertility. We hypothesized that activating SirT1 would maintain female fecundity into late life. SirT1 is an NAD+ dependent histone deacetylase, whose activity is regulated by the nicotinamide to NAD+ salvage pathway, especially the rate‐limiting enzyme NAMPT. In order to increase SirT1 activation via NAMPT, we fed N. guentheri a diet containing the polyphenol resveratrol (RSV) at 300 μg RSV/g food, beginning at sexual maturity. Our previous work showed that RSV‐fed fish at 5 months of age had significantly increased ovarian NAMPT protein levels, and our current data confirms that this result continues into late life (9+ months of age). Furthermore, we found an age‐related decline in NAMPT protein that was overcome by RSV supplementation. For the first time, we show that SirT1 activity, which declines with age, is preserved in the ovaries of our RSV‐fed model. Female N. guentheri fed RSV into late life also showed increased embryo production compared to those on Control diet without RSV. These results suggest that activating SirT1 via increasing NAD+ may have a positive effect on female fertility, and that dietary interventions may become an effective therapy to combat reproductive senescence.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Obesity and Heart Steatosis: the Potential Role of the Receptor for Advanced Glycation End Products (RAGE)
Authors: Romanelli Massimiliano Marco Corsi , Vianello Elena , Tacchini Lorenza , Bandera Francesco , Dozio Elena 
Published: June 2021

Obesity is one of the leading risk factors for cardiovascular diseases. Most of the obesity‐related complications are due to the ectopic accumulation of fat in tissues different from the adipose one, as liver and heart, a condition that can promote organ damage and dysfunction. The receptor for the advanced glycation end products (RAGE) is up‐regulated in many tissues in obesity and has been related to ectopic lipid accumulation in the liver. No data are available about RAGE and heart steatosis, instead.By using lean (n = 5) and obese non‐diabetic (n = 5) Zucker rats (age: 20 weeks) (investigations have been conducted in conformance with the FASEB Statement of Principles for the use of Animals in Research and Education. Protocol Number 325/2015PR – 2015/04/05, Italian Ministry), we tested the hypothesis that in obesity, the accumulation of lipids in the heart may be mediated, at least in part, by RAGE.Heart tissues were studied in terms of lipid accumulation, RAGE tissue expression, activation/modification of specific genes (n=84) involved in lipid metabolism (RT2 Profiler PCR Array, PARN‐007Z, QIAGEN). The following methods were used: red oil staining, real time RT‐PCR and Western blot.We did not observed any difference in heart fat content between lean and obese rats. Heart RAGE levels, both as gene and protein, were almost the same in the two groups. Among the 84 genes evaluated, 6 genes were significantly up‐regulated, of which 4 promoting fatty acid metabolism (Acaa2, Acadl, Acadm, Acot9), 1 fatty acid transport (Crat) and 1 tryacilglycerol metabolism (Gpd1).Uncomplicated obesity in 20‐week old rats is not associated with fat accumulation in the heart. The lack of RAGE hyper‐expression and the increased fatty acid metabolism seem to play a protective role against fat‐induced heart damage.Whether fat accumulation may be promoted by aging and the onset of obesity‐related complication (i.e. diabetes) needs to be explored.Support or Funding InformationUniversità degli Studi di Milano and IRCCS Policlinico San DonatoThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Short‐term Changes in Left Ventricular Dyssynchrony Leads to Congestive Heart Failure
Authors: Hurtado Jasmin Jessica 
Published: June 2021

Ventricular dyssynchrony (VD) may lead to congestive heart failure (CHF). VD is characterized by a difference in the timing of contractions in the ventricles of the heart and has become a prominent pathophysiological feature of CHF. While studies have been done to understand the long‐term effects of VD that lead to CHF, little is known on the short‐term changes associated with VD. This study explores the acute effects of induced VD in‐vivo. Animals will undergo left ventricular pacing to induce VD and changes in mitochondrial structure and function will be analyzed to determine if abnormalities lead to apoptosis and cardiac remodeling. In this study, tissue homogenates from control and paced animals will be used to perform western blot analysis to investigate the changes in expression of mitochondrial respiratory chain complexes and proteins involved in apoptosis. We will measure adenosine triphosphate levels (ATP) to assess overall mitochondrial function. It is expected that VD increases cell death as a result of mitochondrial dysfunction, leading to activation of a fibrotic response. Immunohistochemistry will be used to investigate neutrophil infiltration and myofibroblast formation to confirm the activation of a fibrotic response. We will also evaluate reactive oxygen species and matrix metalloproteinases activities, which implicate cell injury and death that results in cardiac remodeling. We hypothesize that induced left ventricular pacing in a non‐congestive heart failure model will create short‐term changes that alter cardiovascular structure and metabolism. It is important to understand the short‐term physiological changes that result from dyssynchrony because electro‐mechanical conditions found in the absence of CHF can result in long‐term effects that may eventually lead to CHF.Support or Funding InformationThis research project will be supported through FATSA funding by Dr. Katrina Yamazaki.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Clinical Biomarkers of Congestive Heart Failure Significantly Correlate with Pancreatic Trypsin and Lipase Levels in Human Blood Plasma
Authors: Courelli Vasiliki , Courelli Asimina , Mills Paul , Schmid‐Schoenbein Geert 
Published: June 2021

We recently have shown that pancreatic enzymes entering the circulation after a rise in intestinal permeability may cause multiple organ dysfunctions. Increased intestinal permeability occurs in congestive heart failure (CHF), for example due to reduction of cardiac output with hypoperfusion of the small intestine. We hypothesize that elevated intestinal permeability during CHF allows digestive enzymes, such as pancreatic trypsin and lipase, typically found in the lumen of the small intestine, to enter the systemic circulation. Our goal is to determine the levels of pancreatic trypsin and lipase and their correlation with clinical biomarkers of inflammation, and functional measurements of the heart and sympathetic nervous system. Blood from 35 (19 CHF and 16 non‐CHF Controls) patients at rest and analyzed by Western Blot for pancreatic lipase and trypsin and for inflammatory markers by ELISA assays for TNF‐a, IL‐6, BNP, ICAM, p‐Selectin, CRP, differential leukocyte counts and adrenergic sensitivity assays using isoproterenol. Clinical measurements such as age, body weight, BMI, and cardiac ejection fraction were recorded. The results showed significantly higher levels of trypsin, lipase, as well as TNF‐a, IL‐6, BNP, p‐Selectin, CRP, and neutrophil count. No change in monocyte, eosinophil, and basophil counts of CHF patients were seen when compared to Control. There were significant correlations between pancreatic trypsin levels and TNF‐a, BNP, and neutrophil count, and also between pancreatic lipase and TNF‐a, IL‐6, BNP, CRP, p‐Selectin, ejection fraction, neutrophil count, and Isoproterenol response. These results suggest that the protein levels of pancreatic digestive enzymes in the systemic circulation are elevated. The levels correlate with functional metrics of CHF and potentially play key roles as CHF biomarkers and in the analysis of the loss of cardiac function.Support or Funding InformationNational Institutes of Health Grant GM 85072This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Elastic lamina fragmentation in sickle mice can be rescued by JNK‐Cathepsin inhibition
Authors: Song Hannah , Keegan Philip M. , Denby Avery J. , Clark Alexus , Selma Jada , Anbazhakan Suhaas , Botchwey Edward A. , Platt Manu 
Published: June 2021

Sickle cell disease (SCD) is the most common inherited blood disorder, affecting 100,000 people domestically, and an additional 300,000 babies with SCD are born globally each year. Children with sickle cell anemia have increased stroke risk, but mechanisms underlying arterial vasculopathy are not well defined. Previously, we have shown that adhesion of peripheral blood mononuclear cells (PBMCs) from people with SCD to human aortic endothelial cells (ECs) significantly increased active cathepsin K and V enzymes compared to wildtype PBMCs suggesting that inflammatory cells from SCD contribute to pathologic vascular remodeling. In this study, Townes humanized knock‐in sickle transgenic mice were used to test the hypotheses to decode mechanisms developing cerebral vasculopathy and to pursue pharmaceutical intervention studies to hamper vascular remodeling. Carotid arteries from sickle mice (SS genotype) showed elastic lamina fragmentation as early as 3 weeks old compared to heterozygous littermate controls (AS) quantified by significantly higher elastin break numbers per artery (n=4, p<.05). In addition, expression of cathepsin K, a powerful elastase, was increased in carotid arteries in SS mice measured by immunostaining, and active cathepsin K and V were detected in aortas of SS mice by zymography confirming accelerated proteolytic degradation. To block upstream signaling to cathepsin K and reduce elastin fragmentation and arterial remodeling, c‐jun N‐terminal kinase (JNK) was inhibited with SP600125 by daily intraperitoneal injections for 8 weeks from 3‐week‐old age (3wk+8wk treatment) or from 11‐week‐old (11wk+8wk treatment). We hypothesized that inhibiting JNK/cathepsin pathway at earlier age will prevent the onset of arterial remodeling, and at later age, we might be able to regress the arterial remodeling or at least to halt the progression of elastin fragmentation. Accordingly, SP600125 injection significantly reduced carotid arterial remodeling indicated by elastin fragmentation and artery perimeters in SS mice at younger age. This suggests that arterial remodeling due to sickle cell anemia is mediated by JNK signaling, perhaps through cathepsin K proteolysis of elastin, and more importantly, that this occurs in Townes SS mice, demonstrating their utility for mechanistic studies of arterial vasculopathy and complications due to sickle cell anemia.Support or Funding InformationAHA, NIHThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
siRNA Mediated Knockdown of MLF1 Gene Suppressed the Proliferation and Colony Forming Ability of Human Lung Cancer Cells.
Authors: Wang Hongtao , Yang Jin , Zhu Guoliang , Yan Ruxue , Zhang Yao , Wang Xiaojing 
Published: June 2021

BackgroundLung cancer is a malignant lung tumor characterized by uncontrolled cell growth in tissues of the lung. Myeloid leukemia factor 1 (MLF1) is a protein involved in myeloid cell differentiation which regulates the cell cycle and the expression of numerous genes. The role of MLF1 in hematologic cancers is well established, As yet, there is little knowledge of MLF1 expression and biological function in lung cancer. Here, we investigated the role of MLF1 in lung cancer using a variety of cell lines along with patient samples to determine whether MLF1 played a significant role in this devastating disease.Materials and MethodsLung cancer cell lines (A549, H1975, HCC827, and NCI‐H460) and primary lung tissue were used to assess the relative levels of MLF1 in lung cancer. The lung cancer cell line A549 was lentivirally transfected to silence endogenous MLF1 gene expression, which was confirmed by real‐time quantitative PCR (qPCR). Cell proliferation was assessed through fluorescence imaging and MTT assays. Cell cycle analysis was performed utilizing flow cytometry and formation of cell colonies evaluated microscopically.ResultsProliferation of A549 cells was significantly inhibited in cells where MLF1 was silenced compared to controls. Cell cycle analysis indicated that cell cycle phases were not significantly changed upon silencing of MLF1 in lung cancer cells. A significant increase in apoptosis was observed in MLF1‐knockdown cells, while a significant decrease in number of cell colonies formed was observed in MLF1‐knockdown cells compared to controls. In most, but not all, human lung cancer tissue samples MLF1 was upregulated.ConclusionIn summary, MLF1 promotes the proliferation and colony forming abilities of lung cancer cells and significantly decreases apoptosis while have no impact on cell cycle. Further studies with larger sample sizes are needed 1) to conclude whether human lung cancers upregulate MLF1, 2) to reveal the mechanism of action for MLF1 in lung carcinogenesis and 3) investigate MLF1 gene therapy for the treatment of lung cancer.Support or Funding InformationThis work was supported by Key Program of Natural Science Research of Higher Education of Anhui Province (Grant KJ2016A472 KJ2017A241), Key program for excellent young talents in college and university of Anhui province (Grant gxyqZD2016168), National Natural Science Foundation of China (Grant 81772493), and College students' innovation and entrepreneurship training project (Grant 201610367007)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The effects of methylmercury on breast cancer cells in Danio rerio
Authors: Cressey Lauren , Christensen Emily , Conn Brandon , Morrow Sara , Zhang Raymond , Benoit Janina , Gaudet Hilary 
Published: June 2021

Metalloestrogens are small ionic metals that activate the estrogen receptor (ER). Studies have shown that when metalloestrogens bind to the ER, there is an increase in transcription and expression of estrogen‐regulated genes, which induces proliferation of estrogen‐dependent breast cancer. Methylmercury (MeHg), a metalloestrogen, is present in the environment and is toxic at moderate to high concentrations. However, at lower concentrations MeHg may promote the proliferation of ER‐positive breast cancers and protect cells against pro‐apoptotic signals. To investigate the effects of MeHg treatment on breast cancer cells in vitro, MCF7 breast cancer cells were treated with concentrations of MeHg ranging from 1 nM to 100 mM. MeHg analysis was used to quantify intracellular mercury concentrations and cell proliferation and apoptosis were determined by cell counting and Annexin‐V staining, respectively. We defined a protocol that maximizes cellular exposure to mercury and we found that treatment of human ER‐positive breast cancer cells with 1 nM MeHg promoted proliferation, while treatment with a concentration of 100 nM induced apoptosis. Investigations into the effects of MeHg treatment of zebrafish on breast cancer growth and progression are currently underway. Clarifying the effects of MeHg on breast cancer will improve our understanding of how environmental toxins affect tumor progression and may lead to the development of future therapeutic strategies.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
OTUD7B upregulation predicts a poor response to paclitaxel in patients with triplenegative breast cancer
Authors: Lin Yuan‐Feng , Chiu Hui‐Wen , Hsiao Michael 
Published: June 2021

Paclitaxel is a first‐line chemotherapeutic for patients with breast cancer, particularly triple‐negative breast cancer (TNBC). Molecular markers for predicting pathologic responses to paclitaxel treatment is thus urgently needed since paclitaxel resistance is still a clinical issue in treating TNBCs. We investigated the transcriptional profiling of consensus genes in HCC38 (paclitaxel‐sensitive) and MDA‐MB436 (paclitaxel‐resistant) TNBC cells post‐treatment with paclitaxel. We found that OTUD7B was downregulated in HCC38 but upregulated in MDA‐MB436 cells after paclitaxel treatment at cytotoxic concentrations. Moreover, our data showed that OTUD7B expression causally correlated with IC50 of paclitaxel in a panel of TNBC cell lines. Moreover, we found that OTUD7B upregulation was significantly detected in primary breast cancer tissues compared to normal breast tissues but inversely correlated with tumor growth in TNBC cells. Besides, the increased levels of OTUD7B transcript appeared to causally associate with invasive and metastatic potentials in TNBC cells. In assessments of recurrence/metastasis‐free survival probability, high‐levels of OTUD7B transcripts strongly predicted a poor prognosis and unfavorable response to paclitaxel‐based chemotherapy in patients with TNBCs. In silico analysis suggested that OTUD7B regulation, probably owing to miR‐1180 downregulation, may negatively regulate the NF‐kB‐Lin28 axis which in turn triggers Let‐7 microRNA‐mediated caspase‐3 downregulation, thereby conferring paclitaxel resistance in TNBCs. These findings suggest that OTUD7B may be a useful biomarker for predicting the anti‐cancer effectiveness of paclitaxel and could serve as a new drug target for enhancing the canceridal efficiency of paclitaxel against TNBCs.Support or Funding InformationThis study was supported by the Ministry of Science and Technology, Taiwan (MOST 105‐2320‐B‐038‐021‐MY3 and MOST 104‐2320‐B‐038‐061‐MY3)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Suppression on Adipocyte Differentiation of Human Bone Marrow‐Derived Mesenchymal Stem Cell (hBMSC) by a Phytoestrogen Diarylheptanoid
Authors: Sutjarit Nareerat , Weerachayaphorn Jittima , Suksamrarn Apichart , Blair Harry Colbert , Piyachaturawat Pawinee 
Published: June 2021

Osteoporosis is a common metabolic bone disease characterized by low bone mineral density and increased risk of fractures in elderly. Low bone mass in osteoporosis is often associated with an increase in bone marrow adipogenesis. Marrow adipocytes secreted a number of bioactive molecules that suppress osteoblast differentiation leading to bone loss. The inhibition of marrow adipogenesis with an increase in osteogenesis is one of the potential therapeutic interventions for treatment of osteoporosis in postmenopausal and aging women. The present study investigated the effects of a diarylheptanoid phytoestrogen, (3R)‐1,7‐diphenyl‐(4E, 6E)‐4,6‐heptadien‐3‐ol (DPHD) from Curcuma comosa (Zingiberaceae family) on human bone marrow‐derived mesenchymal stem cell (hBMSC) proliferation and adipogenic differentiation. DPHD (0.1–10 μM) increased hBMSC cell proliferation but inhibited adipogenic differentiation, maturation of adipocytes with suppressions of adipogenic genes and proteins; peroxisome proliferator‐activated receptor γ (PPARγ), lipoprotein lipase (LPL) and fatty acid binding protein 4 (FABP4). In addition, the anti‐adipogenic activity of DPHD at 0.1 and 1 μM were abolished by ICI 182, 780, an estrogen receptor (ER) antagonist whereas the anti‐adipogenic activity of 10 μM of DPHD was not completely inhibited by ICI 182, 780. Therefore, the anti‐adipogenic activity of DPHD particularly at low dose is, at least, mediated through ER. The investigation on the non‐estrogenic effect of anti‐adipogenic effect of DPHD is undergoing.Supported by Mahidol University research grant and the Science Achievement Scholarship of Thailand (SAST).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Tissue Morphology and Expression of Myelin Basic Protein and Inducible Nitric Oxide Synthase in Wistar Rats Treated with Sodium Arsenite: The Beneficial Effects of Ethanol Leaf Extract of Tridax Procumbens
Authors: Samuel Ekundayo Stephen , Olopade James Olukayode , Gbadegesin Michael Adedapo , Odunola Oyeronke Adunni 
Published: June 2021

Arsenical compounds cause significant issues in both humans and animals including an increased risk of developing cancer. In the present study, the role of Tridax procumbens leaf extract (TPLE) on the toxicities caused by sodium arsenite in rats was assessed. Thirty‐two male Wistar rats (80–100 g) were equally assigned into four groups (A–D) and treatment was as follows: Group A (control) were administered 1 ml/kg body weight (bwt.) olive oil; B: 2.5 mg/kg bwt sodium arsenite (SA); C: 100 mg/kg bwt TPLE; D: 100 mg/kg bwt TPLE and 2.5 mg/kg bwt SA. TPLE was administered daily for 14 days while SA was given on day 7 and 14. The route of administration was oral. Histological analysis and expression of inducible nitric oxide synthase (iNOS) (in liver, lung, cerebrum and cerebellum) and myelin basic protein (MBP) (in cerebellum) was performed. Histological examinations showed that sodium arsenite caused disruptive lesions in the liver, lungs and cerebral cortex of rats in group B. However, Tridax procumbens extract ameliorated these effects when co‐administered with arsenite in group D. There was significant elevation (p<0.05) in the expression of iNOS protein in the tissues of rats in group B when compared to other groups as revealed by immunostaining. In addition, the white mater cells of the cerebellum showed significant elevation (p<0.05) in the expression of myelin basic protein in group C as compared to groups A, B and D when quantified. In conclusion, the ethanol leaf extract of Tridax procumbens shows beneficial effects against sodium arsenite induced toxicities in Wistar rats.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.