bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ganoderma lucidum extract decreases motility and lamellipodia formation of triple‐negative metastatic breast cancer
Authors: Acevedo‐Diaz Ariana C , Ortiz‐Soto Gabriela , Suarez Ivette J , Zayas Astrid , Martinez‐Montemayor Michelle M 
Published: June 2021

Breast cancer (BC) is the leading cause of cancer among women in the United States and Puerto Rico. Triple‐negative breast cancer (TNBC) is characterized by the absence of estrogen and progesterone receptors, and lack of HER2 overexpression. Approximately, 15% of all women with TNBC typically display shorter overall survival and an early peak of distant recurrences at 3y after diagnosis. Treatments for TNBC are limited; currently, there are no approved targeted therapies besides non‐targeted chemotherapy. The mortality of TNBC could result from the lack of effective treatments to decrease the migration of cancer cells to other tissues. Hence, it its highly important to understand these migration processes and to find effective therapies. Therefore, we aimed to test the anti‐migration effects of the medicinal mushroom Ganoderma lucidumextract (GLE) on TNBC cell motility and on the regulation of proteins involved in this process. First, MDA‐MB‐231 cells were treated with various GLE concentrations and evaluated for cell viability and a washout assay. To study the effect of GLE on cell migration, cells were treated with vehicle, 0.25 or 0.96mg/mL (IC50) of GLE for 24h, followed by wound healing and invasion assays. The activity of Rac was tested by a pulldown activity assay and immunoblotting. Furthermore, we tested the expression of proteins important in the dynamics of cell motility Cdc42, Lamellipodin (Lpd), FAK, WAVE and Rho. The localization and expression of Lpd was visualized by immunocytochemistry. Results showed that GLE significantly decreased the cell viability on TNBC, with no cell recovery after a 72h period of treatment withdrawal. GLE significantly decreased MDA‐MB‐231 cell migration and invasion, while reducing the activity of Rac. The expression of Lpd, FAK, WAVE, c‐myc, and Cdc 42 were also modulated upon GLE treatment. GLE decreased Lpd localization in ruffled edges of cancer cells, as well as changes in nuclear and cell morphology. In conclusion, our results suggest the potential of GLE as a natural anti‐TNBC migration agent.Support or Funding InformationThis work was supported by grants from the National Institutes of Health GM111171 (MMM), MD007583 (MMM), GM103475 INBRE‐Supplies for Graduate Students (GOS), from the Puerto Rico Science, Technology and Research Trust (PRSTRT) SGRP 2017‐043, PRSTRT Hurricane Relief Funds, and from the U.S. Dept of Education Title‐V‐PPOHA P031M105050 and Title‐V‐Cooperative P031S130068. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health, the Puerto Rico Science, Technology and Research Trust or the U.S. Department of Education.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Deletion of Arid1a in osteosarcoma enhances aggressive cell phenotypes
Authors: Fatema Kaniz , Ranjit Arina , Barrott Jared , Habashi Ali 
Published: June 2021

Osteosarcoma is a form of bone cancer that primarily affects children and young adults. 30 years ago survival rates went from 20% survival to 75% survival with the introduction of aggressive chemotherapy combined with surgery. For the past three decades the survival rate has remained the same despite the increase in targeted therapies to treat other cancers. Our research is aimed toward discovering new drugs that can treat patients that do not respond to traditional chemotherapy. With recent cancer discoveries, osteosarcoma has been identified as a genetically complex disease. In a forward genetic screen using the transposon piggyBac, we discovered a strong correlation between Arid1a gene repression and increased osteosarcoma rates. The ARID1A protein plays a role in epigenetics by directing chromosomes to unwind from histones. In an attempt to discover whether ARID1A contributes to sarcomagenesis, osteosarcoma cell lines were grown in culture dishes. Using CRISPR/Cas9 gene editing, the ARID1A gene was disrupted from the main sequence and various methods were used to test proliferation rates. Not only are we testing gene disruption in cell lines, but we are also testing mouse models that have had Arid1a knocked out to determine if osteosarcoma growth rates increased. Our long term goal is to provide a therapy that can be tested in humans with osteosarcoma to help those who do not respond to traditional chemotherapy and provide an alternative therapy with potentially less side effects.Support or Funding InformationIdaho INBREIdaho State University Start UpThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
MacroH2A Variant Suppress Uveal Melanoma Progression and Rewires Cancer Metabolic Phenotype
Authors: Longhitano Lucia , Giallongo Sebastiano , Caltabiano Rosario , Reibaldi Michele , Longo Antonio , Russo Andrea , Fallico Matteo , Tibullo Daniele , Distefano Alfio , Nicolosi Daniela , Lazzarino Giuseppe , Volti Giovanni Li 
Published: June 2021

Histone are a family of protein conserved among all the eukaryotes. A histone variant part of the H2A histone family is macroH2A1 which is expressed in nearly all cell types and is involved in a number of processes including cell cycle, gene regulation, DNA damage repair and senescence. Melanoma of the uveal tract, or uveal melanoma (UM), though rare, is one the most common primary cancer of the eye. Its incidence is approximately 4.3 new cases per million people in the United States. Metastasis is a frequent occurrence in uveal melanoma, and outcomes are poor once distant spread occurs and no clinically significant chemotherapeutic protocol is so far available.The aim of the present study was to evaluate the relationship between macroH2A1 and UM progression. We established a stable knockdown of the protein, using a specific macroH2A1 shRNA and assessed differences in cell proliferation, migration and metabolic profile.Cell proliferation, migration and colony formation capacity were evaluated by Xcelligence technology, wound healing assay and clonogenic assay. Mitochondrial respiratory chain gene expression was evaluated by RT‐PCR and confirmed by immunocytochemistry whereas metabolic phenotype was determined by Seahorse technology. Our results were further confirmed in a series of human UM biopsies obtained and results were correlated to survival, metastatic outbreak and proliferative index. The study was conducted according to the basic principles of the declaration oh Helsinki. Our results showed that knockdown for macroH2A1 resulted in a reduced proliferation, migration and colony capacity formation rate when compared to their control. Using seahorse assay we also demonstrated that the knockdown of macroH2A1 induced a shift in cell metabolism. These results were confirmed by RT‐PCR and immunocytochemistry showing that knockdown for macroH2A1 had a significant decreased expression of genes implicated in oxidative phosphorylation and in NAD+ metabolism, and a decreased level in TFAM expression. Finally, these data were confirmed in UM biopsies, exhibiting increased expression of macroH2A1 inpatients deceased for metastasis. Furthermore, p16, a well‐established marker of cell proliferation, correlated with macroH2A1 expression. In conclusion, our results showed that macroH2A1 play a major role in UM progression and may represent a possible target for future chemotherapic strategies.Support or Funding InformationThis work was supported by FIR2016/2018 from the University of CataniaThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The effect of experience with phonological sequences on the suppression effect, used to assess echoic sensory memory, within the auditory‐evoked potentials (AEPs)
Authors: Kalontar Enessa , Hervey Olivia , Wagner Monica 
Published: June 2021

Specific Language Impairment (SLI), a developmental language disorder, has been associated with deficits in working memory (Gathercole, 2006). Using magnetoencephalography (MEG), Helenius and colleagues (2009, 2014) have shown that adults and children with SLI have impaired sensory memory for the repetition of meaningful spoken words. Also, of interest is whether individuals with SLI show impaired sensory memory for phonological sequences, which would likely affect vocabulary learning. As a first step in pursuing this question, we examined the effects of experience with phonological sequences on the suppression effect used to assess sensory memory. The suppression effect, is a reduced response within the auditory evoked potentials (AEPs) or its magnetic counterpart, to repetition of an auditory event, including phonological sequences. EEGs were recorded from 24 native‐English and 24 native‐Polish adults as they listened to same and different non‐word pairs within two experimental sessions. Non‐word pairs contained a phonological sequence contrast, /st‐sət/that occurs in the English and Polish languages and a contrast /pt‐pət/that occurs only in the Polish language. The EEG was time locked to the second word in the non‐word pairs, which was the same non‐word in the same pairs (pətilɑ‐pətilɑ) and different pairs (ptilɑ‐pətilɑ). Thus, a larger AEP response to the second word in the different pairs relative to the second word in the same pairs indicates that the brain registered the additional sound in the different pair. Likewise, evidence of the suppression effect within the same pairs suggest an intact sensory memory for the phonological sequences within the first non‐word. Preliminary examination of results at averaged fronto‐central electrode sites within the AEP revealed an effect of language experience between ~400–600 ms post‐word onset. The native‐Polish listeners showed a larger response to their native language /pt‐pət/contrast than the English listeners and the English listeners showed a larger response to the /st‐sət/contrast that is more prominent in the English language than the Polish language. Thus, native‐language experience and frequency of phonological sequences within a language should be considered when assessing sensory memory in clinical populations.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Deletion of Arginase 2 reduces neurodegeneration in a model of Multiple Sclerosis
Authors: Palani Chithra D. , Liu Fang , Xu Zhimin , Fouda Abdelrahman , Caldwell Ruth B. , Narayanan S. Priya 
Published: June 2021

PurposeVisual impairment due to optic neuritis is a major clinical feature of Multiple Sclerosis (MS), and can lead to temporary or permanent vision loss. Previous studies from our lab have demonstrated the critical involvement of arginase 2 (A2) in retinal neurodegeneration. The current study was undertaken to investigate the role of A2 signaling in MS mediated retinal neuronal damage.MethodExperimental Autoimmune Encephalomyelitis (EAE) was induced in WT mice and A2 knock out (A2 KO) mice (both on C57Bl6 background) according to established procedures. Briefly, WT and A2 KO mice were immunized by subcutaneous injections of an emulsion containing MOG35‐55 peptide (300 μg/mouse) along with Complete Freund's adjuvant (CFA, killed Mycobacterium tuberculosis H37Ra, 400 μg/ul). Each mouse additionally received 300 ng of pertussis toxin (PT, Sigma, St. Louis, MO) by i.p. injection in 200 μl of PBS on day 0 and day 2 post‐immunization. Control group will be immunized with CFA without antigen (MOG), and two doses of PT will be given on day 0 and 2. Clinical disease scores were monitored daily in all groups in a blinded fashion by measuring paralysis according to the conventional grading system. Neurodegeneration studies were performed using retinal flatmount analysis. Expression of arginase and the downstream signaling molecules were examined by Western blotting, and inflammatory molecules were analyzed by qPCR.ResultsIncreased expression A2 was observed in WT retinas in response to EAE induction. EAE‐induced motor deficits and body weight loss were markedly reduced in A2 KO mice compared to WT controls. Retinal flat mount studies demonstrated a significant reduction in the number of Brn3a positive and NeuN positive neurons in WT EAE retina (p<0.01; N=6–10) in comparison to normal control mice. A significant increase in the number of surviving neurons (NeuN‐positive and Brn3a‐positive) was evident in retinas of EAE‐induced A2KO mice compared to WT (p<0.05; N=6–10). RNA levels of proinflammatory molecules such as CCL2 ((C‐C motif) ligand 2), COX2 (Cyclooxygenase‐2), IL1a (Interleukin 1a), IL12a, and IL‐18 were significantly reduced in the A2KO EAE retinas compared to WT EAE (p<0.05, N=5–6). Signaling studies showed increased levels of phospho‐ERK1/2 and reduced levels phospho‐BAD in the WT EAE retina, while these changes were normalized in EAE‐induced A2 retinas.ConclusionOur studies establish EAE as an excellent model to study MS‐mediated retinal neuronal damage and suggest the potential value of targeting arginase 2 signaling as a therapy to prevent MS‐mediated vision loss.Support or Funding InformationThese studies supported by the National Multiple Sclerosis Society (PP‐1606‐08778 to S.P.N) and Augusta University Culver Vision Discovery Institute.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Co‐localization of Glia Maturation Factor and Progranulin in the Human Alzheimer's Disease Brains
Authors: Thangavel Ramasamy , Premkumar Keerthivass , Zahoor Haris , Saeed Daniyal , Iuliia Dubova , Pushpavathi Selvkumar Govindhasamy , Duraisamy Kempuraj , Ahmed Mohammad Ejaz , Raikwar Sudhanshu P , Zaheer Smita A , Iyer Shankar S , Zaheer Asgar 
Published: June 2021

Amyloid plaques (APs) and neurofibrillary tangles (NFTs) are two major neuropathological hallmarks observed in the brains of Alzheimer's disease (AD) patients. Inflammatory mediators released from the activated glial cells and neurons induce neuroinflammation and neurodegeneration thereby exacerbating AD pathogenesis. We have previously shown that glia maturation factor (GMF), a proinflammatory brain protein is upregulated in the brains of AD patients. Additionally, we also found that the upregulated GMF is associated with APs and NFTs in the brains of AD patients. Progranulin a pleiotropic protein that serves as a precursor of active granulin peptides was also shown to be upregulated in the brains of AD patients. However, the association between GMF and progranulin has not yet been studied in the context of neurodegenerative diseases including AD. We analyzed frozen sections of temporal lobe from human AD patients in this study. Here, we investigated whether the upregulated GMF expression is associated with a corresponding increase in progranulin expression in the vicinity of APs in the AD brains using single and double immunohistochemistry and immunofluorescence staining. Our results show that progranulin immunoreactive neurons and activated microglia are present in the temporal cortex region of AD brains. We report increased progranulin and GMF expression in the vicinity of APs. Further, we also report significantly more progranulin expression in the neurons and glial cells in the brains of AD patients. Our data suggest that the increased expression of GMF and progranulin may synergize to play a critical role in neuroinflammation and neurodegeneration thereby exacerbating AD pathogenesis.Support or Funding InformationThis work was supported by the Veterans' Affairs Merit Award I01BX002477 and the National Institutes of Health Grants AG048205 and NS073670 to AZThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Eliciting Differentiation of Human T Lymphocytes into TH1 or TH2 cells with Inorganic Arsenic Exposure
Authors: Jewell Mollie Anne , Nyland Jennifer 
Published: June 2021

A naturally‐occurring element, inorganic arsenic is found around the world in soil. It can contaminate fresh groundwater, where it is at risk of being ingested. Currently, arsenic is considered to be dangerous with chronic exposure and ingestion at 10 ug/L as established by the World Health Organization and the U.S. Environmental Protection Agency. Chronic exposure to arsenic is associated with inflammation, but current studies have show that even at lower doses, there is a link to expression and secretion changes of cytokines within T lymphocytes, particularly with IL‐2 for growth, pro‐inflammatory IFN‐γ and anti‐inflammatory IL‐4. Shifts favoring pro‐ or anti‐inflammatory cytokines can lead to differentiation into TH1 or TH2 cells, which specialize in their immune response. In this study, we aim to investigate how the expression and secretion of these cytokines produced by activated T lymphocytes change as an in‐vitro model of an activated human regulatory immune system. Through our model, we will detect if chronic low level arsenic exposure has the potential to catalyze a change in T lymphocyte function, and therefore overall immune function.Previous studies have utilized various conditions by which to activate and treat T lymphocytes. As a result, there is variation in how these cytokines are predicted to change. For this study, we obtained human T lymphocytes. They were treated over 24 hours with 10 ng/mL of phytohemagglutinin, a known immune activator, and different concentrations of arsenic to develop a dose response curve, from 20 nM to 500 nM. Viable concentration and cytolethality were determined with differential staining and counting. Cell concentration and cytolethality changes were examined with one‐way ANOVA and Bonferroni's Pairwise T‐test. At 50 nM there is a difference in the cytolethality of the cells in the groups treated with arsenic with or without PHA with p < 0.05.Future work will include ELISA assays will be performed on all treatment groups of the cell media collected for IL‐2, IL‐4, and IFN‐γ, followed by gene expression analysis via PCR. Experiments at 50 nM will be repeated as well to verify differences in cytolethality that were identified. Additionally, differential time periods for treatments of arsenic and PHA will be used to more accurately model chronic exposure in the cells. These other time points will analyzed through ELISA and gene expression analyses to inform the model of long‐term change within the cells of the cytokine profiles.Support or Funding InformationThis research is supported by the Salisbury University Department of Biological Sciences, the Salisbury University Honors College, and the Salisbury University Henson School of Science Grant.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The hydrogel‐encapsulated liver X receptor ligand, T0901317, enhances its antitumorigenic effects but eliminates lipogenesis
Authors: Feng Ke , Yang Xiaoxiao , Ma Chuanrui , Chen Yuanli , Han Jihong , Duan Yajun 
Published: June 2021

The anti‐tumorigenic functions of liver X receptor (LXR) ligands have been confirmed in several types of tumors. We previously reported that LXR ligand, T0901317 (T317), inhibited growth of inoculated LLC1 carcinoma and urethane‐induced pulmonary carcinomas by activating IFN‐γ expression in tissues, particularly in macrophages. However, T317 activates fatty acid synthesis to result in severe hepatic lipogenesis and fatty liver. Tissue‐specific activation of LXR, such as in antigen‐presenting cells (APCs) but not in liver, by ligand can enhance inhibition of tumor growth without activation of lipogenesis. Injected naphthylacetic acid modified D‐glycine‐phenylalanine‐phenylalanine‐tyrosine tetra‐peptide (GFFY) can be selectively delivered to APCs, macrophages and dendritic cells (DCs). In this study, we encapsulated T317 with GFFY hydrogel (GFFY‐T317) and determined its effect on tumor growth and hepatic lipogenesis. Compared with oral administration of T317, subcutaneous injection of GFFY‐T317 more potently inhibited LLC1 tumor growth in mice. The inhibition was dependent on induction of IFN‐γ expression in APCs by activating LXR. We further determined that GFFY‐T317 increased M1 type macrophages while reducing M2 cells in the tumor. Meanwhile, GFFY‐T317 enhanced DC maturation and infiltration to tumors. Both CD3+ and CD8+ cells in tumors were also increased, which was associated with activation of IFN‐γ expression. In contrast, tumor angiogenesis was clearly inhibited by GFFY‐T317 in an IFN‐γ‐dependent manner. In addition, GFFY‐T317 had more potent inhibitory effects on urethane‐induced lung tumor than oral administration of T317. More importantly, in these two tumor models, compared with severe liver steatosis by oral administration of T317, injection of GFFY‐T317 had little effect on lipid synthesis/metabolism in the liver, while eliminating T317‐induced liver injury. Taken together, our study demonstrates that the hydrogel‐encapsulated T317 can inhibit lung tumor growth without adverse effect of lipogenesis, indicating the hydrogel‐encapsulated LXR ligand might be a novel therapy for tumor treatment.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.