bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of Calcium Sulfide Nanoclusters in Cell Proliferation of Malignant Lung and Pancreatic Cell Lines
Authors: Torres Geraline Trossi , Rosado María Figueroa , Forti Kevin Muñoz , Suarez Edu 
Published: June 2021

Lung and pancreatic cancer are leading cause of cancer deaths in the United States. Despite significant developments in treatments, survival rate for lung and pancreatic cancer patients is low. The diagnosis of these cancers is usually done at later stages, are very aggressive and when treated it affects negatively the quality of life of the patients. Recently, there have been advances in nanomedicine particularly in drug delivery and carrier systems developed to treat many types of cancers including lung, pancreas, breast, and prostate, among others. Calcium and sulfur are expected to be biocompatible with human body due the availability of these elements in our system. We propose the use of Calcium Sulfide (CaS) nanoclusters as an anti‐proliferation agent acting selectively in malignant non‐small cell lung adenocarcinoma (NSCLC HCC827) and pancreatic epithelial carcinoma cells (Mia Paca‐2) without affecting non‐malignant lung cells (MRC5). We hypothesize that CaS nanoclusters will decrease the cell replication in HCC827 and in Mia Paca‐2 cell lines without affecting the MRC5. Cells were treated with DMSO [1%] (vehicle control), etoposide [10μM] (positive control), or CaS nanoclusters [3.8μM] (experimental treatment) at 0‐hours. We performed each assay in quadruplicates according to their incubation time: 24, 48 and 72 hours after a single‐dose exposure to the correspondent treatments. To evaluate the effects of the CaS nanoclusters, we performed BrdU Proliferation Assay to quantify the newly synthesized DNA. The preliminary results showed that there was no significant changes in the pancreatic cell lines Mia Paca‐2 and HCC827 treated with CaS when compared to the controls at 24, 48, and 72 hours. In the MRC5 cell line there was only a borderline significance of 0.056 at 48 hours, which showed an increase in proliferation that confirm previous findings using other methods in our lab. In the following step, we plan to evaluate the effect of CaS in apoptotic and autophagy markers using the same cell lines.Support or Funding InformationNIH‐NIGMS #2R25GM096955This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Phenformin inhibits proliferation of acquired gefitinib resistant non‐small‐cell lung cancer(NSCLC) through the reduction of NAD+/NADH ratio
Authors: Kim Suntae , Kang Keon Wook 
Published: June 2021

Epidermal growth factor receptor(EGFR) tyrosine kinase inhibitors(TKI) including gefitinib and erlotinib are now recommended as a first‐line chemo therapy for NSCLC. Unfortunately majority of NSCLC patients administered with gefitinib showed acquired resistance within 1 yr. To overcome it, second‐ and third‐generation of EGFR inhibitors were developed, but eve0n in the third‐generation of EGFR inhibitors, NSCLCs were found to be resistant and new therapeutic strategies have become necessary.HCC827, a NSCLC cell line were cultured with stepwise escalation of gefitinib over 1 yrs to establish acquired gefitinib resistance HCC827(HCC827‐GR) cells. EGFR exons from 18 to 21(tyrosine kinase domain) in HCC827‐GR were not mutated, and the activities of EGFR tyrosine kinase and its downstream kinases(Akt and Erk) were all downregulated in HCC827‐GR cells compared to HCC827 cells. Because EGFR signaling is critical to the regulation of Warburg effect and oxidative phosphorylation(OXPHOS) in cancer cells, we assessed glucose metabolism in both HCC827 and HCC827‐GR cells. Determination of oxygen consumption rate(OCR) and extracellular acidification rate(ECAR) showed that HCC827‐GR cells mainly use OXPHOS in glucose utilization compared to HCC827 cells. Inhibition of OXPHOS by phenformin, known as a strong complex 1 inhibitor, exhibited significant anti‐proliferative effect in HCC827‐GR cells. Phenformin reduced the NAD+/NADH ratio and decreased cellular aspartate level. Moreover treatment of HCC827‐GR cells with α‐ketobutyrate (AKB) which is an electron acceptor or aspartate significantly reversed inhibition of HCC827‐GR cells proliferation. In conclusion, we propose that phenformin is effective to inhibit cell growth of acquired gefitinib resistant NSCLC and suggest OXPHOS targeting as a potential therapeutic target.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Tryptophan Metabolism and IDO/TDO Expression in Bladder Cancer: A Case‐control Study in Singapore
Authors: Lee Sze Han , Esuvaranathan Kesavan , Chiong Edmund , Thamboo Thomas Paulraj , Choo Shoa Nian , Raman Lata Nee Mani , Mahendran Ratha , Chan Eric Chun Yong 
Published: June 2021

BackgroundBladder cancer (BC) is an expensive malignancy to manage, due to its high recurrence (50% in 5 years) necessitating frequent monitoring. As cystoscopy is expensive and invasive as a surveillance tool, patients' compliance and cancer detection are often compromised. The development of non‐invasive biomarkers of BC is therefore pertinent. Previous in‐house metabonomics demonstrated 100% specificity and 71% sensitivity in detecting BC, and discovered lower urinary tryptophan and higher kynurenic acid in BC1. Tryptophan is converted to kynurenine (precursor of kynurenic acid) via reactions mediated by indoleamine 2,3‐dioxygenase 1 (IDO) and tryptophan‐2,3‐dioxygenase 2 (TDO). The perturbation of tryptophan metabolism and IDO has just been recently reported in BC2,3, and newly targeted with IDO and PD‐1 inhibitors in a Phase 1/2a trial4.ObjectivesWe aim to investigate plasma and urinary tryptophan‐associated metabolites and bladder mucosae IDO/TDO expression in a single‐center case‐control study in Singapore.MethodsBC patients and matched controls were recruited at the National University Hospital Singapore Urology Centre. Blood plasma and urinary tryptophan‐associated metabolites were measured via liquid chromatography‐mass spectrometry, while protein expression of IDO/TDO was assessed via immunohistochemistry on bladder mucosae (BC patients' tumor and healthy margin only).ConclusionNew knowledge in tryptophan metabolism and IDO/TDO expression in BC will pave way for new diagnostic and therapeutic modalities for the malignancy.Support or Funding InformationNational University Health System‐Global Collaborative Centre Seed Grant (NUHSRO/2015/065/GCC/02)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Characterization of Drug Resistance Protein Expression Levels in Human Melanoma Cells and Subsequent Treatment with Antifungal Agents
Authors: Koh David W. , McKamey Shelby G. , Daghistani Ayah T. , Jira Lukas R. , Blake Steven D. 
Published: June 2021

The multidrug resistance (MDR) phenotype allows cancer cells to display decreased sensitivity to chemotherapy. A well‐characterized drug resistance gene in cancer is MDR1, which encodes for the p‐glycoprotein/ATP‐binding cassette (ABC) transporter. Lesser known are the roles of the multidrug resistance‐associated protein 1 (MRP1) and lung resistance‐related protein (LRP) in melanoma. Because of the previously demonstrated presence of MRP1 and LRP in human melanoma cells and the continued difficulty of overcoming MDR in melanoma treatment, here we characterized the expression levels of drug resistance genes in melanoma cell lines derived from human patients and determined their susceptibility to novel antifungal treatment. Expression levels were determined by real‐time PCR (qPCR) and immunoblot analyses. Susceptibility of cell lines to antifungal agents was analyzed by flow cytometry, cell proliferation assays, and immunoblotting after drug treatments.Several lines of human melanoma and normal skin cells were analyzed. MDR1 expression was observed in multiple melanoma lines, while increased levels of MRP1 were observed in normal skin cells and one melanoma line. Interestingly, LRP expression was highest in normal skin cells and several melanoma lines. Novel treatment with clotrimazole, an agent previously shown to eradicate melanoma cells, caused significant decreases in proliferation and increases in cell death in all MDR melanoma lines. No extensive cell death was induced by clotrimazole treatment in noncancerous human skin cells. These results indicated that clotrimazole selectively induces cytotoxicity in drug‐resistant melanoma lines. However, decreased efficacy was observed in melanoma lines that overexpressed LRP, as compared to all other melanoma lines that overexpressed MDR1 and/or MRP1. These results indicated that LRP, mostly known for facilitating drug resistance in lung and breast cancer, may also have a significant role in the ability of melanoma cells to resist the effects of conventional melanoma treatments.In conclusion, this study demonstrated the existence and differential expression levels of MDR1, MRP1, and LRP in melanoma and normal skin cell lines. Although all melanoma lines were susceptible to treatment with clotrimazole, decreased efficacy was observed in melanoma lines that overexpressed LRP. Taken together, we conclude that clotrimazole has in vitro efficacy toward the treatment of drug‐resistant human melanoma cells. However, these preliminary studies also indicated that LRP is potentially a significant facilitator of drug resistance in human melanoma.Support or Funding InformationThis research was funded by the Ohio Northern University Summer Research Stipend.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Deletion of Rap1 Increases Atherosclerosis Development in ApoE−/− Mice by Increasing Macrophage Infiltration and Foam Cell Formation
Authors: Chen Xinyi , Xu Aimin , Tang Eva Hoi Ching 
Published: June 2021

The telomere‐binding protein, repressor activator protein 1 (Rap1) was recently found to exert many unexpected physiological functions. The present study aimed to investigate whether deletion of Rap1 modulates macrophage behaviors and affects the development of atherosclerosis in mice. Genetic deletion of Rap1 significantly increased the migration ability of macrophages as illustrated by enhanced chemotactic responses towards monocyte chemoattractant protein 1 (CCL2) and macrophage inflammatory protein‐3‐beta (CCL19). Deletion of Rap1 significantly enhanced cholesterol uptake from modified lipoproteins in macrophages and its transformation into foam cells by increasing the expression of scavenger receptor A. To study the effect of Rap1 deletion on atherosclerotic plaque development, Rap1−/−/ApoE−/− double knockout mice were generated and fed a western diet for 10 weeks. Though total plasma cholesterol, triglycerides and LDL cholesterols were not altered, both the plaque size at aortic root and aortic arch were significantly increased in Rap1−/−/ApoE−/− mice as compared to Rap1+/+ApoE−/− mice. The plaques of Rap1−/−/ApoE−/− aggregated greater amount of lipid deposits, as indicated by enhanced Oil red O staining within the lesions. Macrophage content was significantly increased in plaques of Rap1−/−ApoE−/− mice as compared to Rap1+/+ApoE−/− controls, while collagen content and vascular smooth muscle cells were decreased. Taken as a whole, deletion of Rap1 promotes plaque growth and decreased plaque stability in ApoE−/− mice. In summary, deletion of Rap1 regulates macrophages behaviors, including promotion of its migratory ability and transformability to foam cells and thereby exacerbates the development of atherosclerosis in mice.Support or Funding InformationThis work is supported by RGC General Research Fund (Project code: 17157816), The University of Hong KongThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Intra‐Abdominal Lipectomy Reduces Large Arterial Stiffness and Blood Pressure in Metabolic Syndrome
Authors: Soler Amanda A. , Hutcheson Brenda , Yang Jenny , Hunter Ian , McEvoy Kyle , Zhang Frank Fan , Joshi Sachindra , Bradford Chastity , Gotlinger Katherine , Falck John , Proctor Spencer , Schwartzman Michal Laniado , Rocic Petra 
Published: June 2021

Increased intra‐abdominal (visceral) adipose tissue is a key feature of the metabolic syndrome. Expansion of visceral adipose tissue and the associated altered adipokine profile are linked to the development of hypertension. While reduction in visceral adipose tissue volume offers cardioprotective effects, the mechanisms underlying these effects remain understudied and unclear. In this study, we removed ~90% of visceral adipose tissue (=~5% body weight) by intra‐abdominal lipectomy and assessed large arterial stiffness, large artery structural matrix components, and blood pressure in a metabolic syndrome rat model (JCR:LA‐cp, JCR). Large artery compliance was significantly decreased in JCR vs. normal (Sprague Dawley, SD) rats (75±2% JCR vs. SD (carotid)) with a concomitant significant increase in MMP12‐dependent elastin degradation (3–6 fold vs. SD). Intra‐abdominal lipectomy normalized large artery stiffness, blocked MMP12 activation and reduced elastin degradation in JCR animals (~75% (carotid) vs. untreated JCR). Likewise, hypertension in JCR animals was significantly attenuated by intra‐abdominal lipectomy (MABP=156±3 mmHg JCR vs. 90±6 mmHg SD vs. 132±4 mmHg JCR+lipectomy). 20‐hydroxyeicosatetraeonic acid (20‐HETE), an arachidonic acid metabolite known to be a potent vasoconstrictor in resistance arteries, was significantly elevated in the visceral adipose tissue of JCR rats (~6 fold vs. SD). Like intra‐abdominal lipectomy, 20‐HETE antagonists restored large artery elasticity, blocked MMP12 activation and elastin degradation and significantly decreased blood pressure (125±3 mmHg JCR+20‐HETE antagonists) in JCR rats. Thus, 20‐HETE may be an important adipokine that mediates, in part, the adverse effects of expanded visceral fat volume in the metabolic syndrome. Its removal and inhibition may provide therapeutic and pharmacological approaches, respectively, for the management of central obesity‐driven large artery stiffness and hypertension in the metabolic syndrome.Support or Funding InformationNational Heart, Lung and Blood Institute (NHLBI): 1F31HL137356‐01This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Effect of Injury by Catheter Balloon in Wistar Rats Through Time, Characterizing Restenosis
Authors: Pereira Noemy Pinto , Fernandes Tiago , de Oliveira Edilamar Menezes 
Published: June 2021

AimRestenosis and Atherosclerosis are a public health problem worldwide. There are many instances where arterial injury needs repair and regeneration to avoid heart failure and death. For example in atherosclerosis, arterial aneurysms, and restenosis after balloon catheter stenosis. The goal of this study was carry on to characterize the animal model of balloon catheter injury, that characterizes restenosis and identify if the lesion persists for long periods. Also, in restenosis we analyzed the neointimal hyperplasia over time, in rats that underwent balloon catheter injury in the left carotid artery characterizing restenosis.MethodsIn order to characterize the animal model of balloon catheter injury in male Wistar rats with approximately 400 grams of body weight (n=5/group) were divided into 4 groups (20, 40, 60 and 80 days after injury) and balloon catheter (Fogarty 2F, Edwards Lifesciences) was used to cause the injury that was performed on the left carotid artery and the right carotid artery was used as the control. After the each time the injury the rats were euthanized and the arteries were removed for histological and morphological analysis. The slides were stained with hematoxylin and eosin and the circumference of the external elastic lamina and lumen were used to calculate the thickness of the neointimal (EEL‐lumen = neointimal; μm). One‐way ANOVA was used with Tukey post‐hoc, presented in the mean ± standard error of the mean. Significance level was p<0.05.ResultsAfter the injury, the endothelium was removed by the balloon catheter. Twenty days after the injury, we observed the neointimal layer formation between the middle tunica and the lumen, resulting of the proliferation and cellular migration towards the vessel lumen. Twenty days after the injury the neointimal was increased (219087.62 ± 54837 (p<.0001) compared with the control group, after 40 days we observed increase compared to the 20 days (250751 ± 4076; (p<.0001), however, after 60 days was decreased (90024 ± 5514 (p<0.005) compared to control group, 20 and 40 days. The neointimal layer was stabilized with 80 days (97886 ± 13546 (p=0.0266).ConclusionThe rats submitted to catheter balloon injury showed an increase in the thickness of the neointimal, characterizing the model as effective to promote mechanical damage in the vessel lumen. These results showed that in the control group the neointimal hyperplasia was null, while the peak of growth was with 40 days after the injury stabilizing with 80 days. Thus, this is an effective model for studies of protocols for the prevention of long‐term restenosis.Support or Funding InformationCAPES, CNPq and FAPESPThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Investigating the Sex‐Based Differences in Lung Inflammation in an Obesity Model of Early Sepsis
Authors: Azraf Ashfaqul , Galkin Simon , Dwivedi Dhruva , Khan Momina , Fox‐Robichaud Alison 
Published: June 2021

BackgroundSepsis is a life‐threatening response to infection and the most common organ to fail is the lung. There is clinical data to support that obese individuals with sepsis may have a survival advantage. We have previously shown that male obese mice have reduced lung injury during early sepsis. There are sex differences in the response to sepsis with women generally having better outcomes. The objective of this study was to determine if obese female mice were also protected from sepsis‐induced lung inflammation.Methods5 week old female C57BL/6 mice, housed in static cages, were randomized to either a high fat Western diet (HFD) (n=12) (Modified Breslow Dyets510151) or normal chow diet (NCD) (n=14) for 15 weeks. Diet restriction to 70% of normal intake was introduced gradually after 6 weeks of ad lib access to control the weight gain of the NCD group. Glycemic control was compared between groups at 14 weeks by a glucose tolerance test where mice were fasted for 6 hours then given 2 g/kg of 20% glucose solution IP follow by glucose measurements at 15, 30, 60 and 120 minutes. At 20 weeks of age sepsis was induced by cecal ligation and puncture with a single 18 ga puncture. All mice received 2 mls of Ringer's lactate subcutaneously prior to surgery and 500 ml immediately post‐surgery and 4 hours later. Animals were euthanized at 6 hrs and tissues and blood collected. Airway inflammation was assessed by quantifying lung myeloperoxidase activity in snap‐frozen lung tissue.ResultsFemale mice fed the HFD diet gained significantly more weight (31.9 ± 1.9 (SE) g compared to 20.9 ± 0.8 g) and had larger livers (1.8 ± 0.2 g vs 0.8 ± 0.04g) compared to the NCD mice. HFD female also had higher glucose levels (peak 24.8 ± 1.8 mmol/l) compared to NCD (peak 16.6 ± 1.6 mmol/l) following a glucose challenge. WBC counts of HFD (1.1 ± 0.1 ×109/l) and NCD (1.1 ± 0.1 ×109/l) septic mice were significantly lower the sham operated mice (HFD 2.7 ± 0.2 ×109/l vs NCD 2.0 ± 0.2 ×109/l). In contrast to our previous findings in septic male mice, there were no significant differences observed in lung myeloperoxidase levels between the HFD and NCD female mice (24.1 ± 2.0 U/mg tissue compared to 27.6 ± 1.6 U/mg tissue).ConclusionsIn female mice fed a HFD weight gain is associated with glucose intolerance. In contrast to our published work in male mice, female obese mice gain significantly less weight and have smaller livers than their male counterparts. Importantly, obesity conferred no protection from early sepsis‐induced lung inflammation compared to NCD fed septic female mice.Support or Funding InformationFunded from an internal funds administered by the Department of MedicineThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Ginsenoside Rg1 Ameliorates Rat Myocardial Ischemia‐Reperfusion Injury by Modulating Energy Metabolism Pathways
Authors: Han Jing‐Yan , Li Lin , Pan Chun‐Shui , Yan Li , Cui Yuan‐Chen , Liu Yu‐Ying , Mu Hong‐Na , He Ke , Sun Kai , Fan Jing‐Yu , Huang Li 
Published: June 2021

BackgroundThe present study was designed to investigate the protective effect and mechanisms of ginsenoside Rg1 (Rg1) against heart ischemia‐reperfusion (I/R) injury, with focusing on energy metabolism.Methods and resultsMale Sprague‐Dawley rats were subjected to 30 min occlusion of left coronary anterior descending artery followed by reperfusion for 90 min. Rg1 (5 mg/kg/hour) was continuous administrated intravenously 30 min before occlusion until the end of reperfusion. Myocardial infarct size, blood flow, myocardial function, structure and apoptosis, energy metabolism and change in Ras homolog gene family, member A (RhoA) signaling pathway during cardiac I/R injury were evaluated. Binding of Rg1 to RhoA was assessed using Surface Plasmon Resonance. Rg1 prevented I/R‐elicited insults in myocardium, including myocardial apoptosis, decreased myocardial blood flow and cardiac dysfunction, alteration in myocardium structure, and apoptosis. In addition, Rg1 restored the production of ATP during cardiac I/R. Furthermore, Rg1 was able to bind to RhoA and down‐regulate the activity of RhoA signaling pathway.ConclusionThese results indicated that Rg1 had protective potential against I/R‐induced myocardial injury, which may be related to inhibiting myocardial apoptosis and modulating energy metabolism through binding to RhoA inactivating RhoA signaling pathway.Support or Funding InformationThis work was supported by the National Natural Science Foundation of China [81273637] for Jing‐Yan Han.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.