bluuebunny/crossref_metadata_2025_split huggingface dataset:
PRECLINIC EVALUATION OF SIRNAS AGAINST VEGFR‐2 FOR THE TREATMENT OF DIABETIC RETINOPATHY
Authors: Juarez Gerardo Vera , Villafaña Santiago 
Published: June 2021

The vascular endothelial growth factor (VEGF) is a group of important proteins in the signaling for vasculogenesis and angiogenesis, it has been reported to participate in the development of diabetic retinopathy (RD), which is the second cause of blindness worldwide, within the VEFG pathway, it has been reported that VEGFR‐2 is the principal involved in RD, for this reason, the aim of this work is to evaluate the expression of VEFGR‐2 in the retina of diabetic rats and also design and synthesize a siRNA to the VEFGR‐2. Wistar rats were inyected with streptozotocin (60mg/kg/i.p), after 4, 8 and 12 weeks the neovascularization was evaluated by junctions and lacunarity, the retina was extracted and the expression of VEFGR‐2 was determined by RT‐PCR. For the siRNA's design, we used Wizard v3.1, RNAfold and EMBOSS software programs, the selected sequences were synthesized with a MERMADE 8 and evaluated. The results obtained showed that there is an increase of junctions and in the levels of VEGFR‐2 and a decrease of lacunarity in the retina with 8 and 12 weeks of diabetes evolution.The evaluation of siRNA suggests that 343–364 and 2621–2641 regions are susceptible to degrade. Preliminary results showed a decrease in the neovascularization when we administrated the siRNAs. Thus, our conclusions are that early diabetes can produce DR and our siRNA maybe could decrease the DR evolution.Support or Funding InformationGrants: Instituto Politécnico Nacional (SIP‐20194983), Programa Institucional de Formación de Investigadores del IPN (BEIFI No. 2062), Scholarship by Consejo Nacional de Ciencia y Tecnología (CONACYT No.630882) and Comisión de Operación y Fomento de Actividades del IPN (COFAA).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Post Stroke Depression: the Mechanisms, Prevention and Therapy Through Holistic Treatment Approach
Authors: Santos Maria 
Published: June 2021

Background/ObjectivesStroke is the third most common cause of disability and second most common cause of death worldwide. At least one‐third of stroke survivors suffer from depression.Depression is a common complication of stroke, leading to increased morbidity and mortality, and is defined as depressed mood on a daily basis for a minimum duration of two weeks.Objective is to investigate the causal associations between post stroke depression and its outcomes. To evaluate the associations between stroke and depression in Nigerians adults living American and in NigeriaMethodInvestigation of post stroke depression in American adults and Nigerian‐American adult living in America and Nigeria.Holistic clinical approach interventions when treating PSD for better outcome than pharmacological only approach. These includes: Adult day care, dietitian, speech therapy, social services, PT, OT, yoga, psycho‐therapy, primary care clinicians, family and friends.Results/discussionStudy participants living with other people did better than those living alone P‐value 0.05.ConclusionStroke has been identified as one of the prioritized non‐communicable diseases the hope is that the promotion and endorsement of new, more‐effective approaches for the prevention of stroke and CVD, in combination with prevention strategies, will change current practice worldwide, thereby saving millions of lives. By complementing cost‐effective individual health‐care interventions with population‐wide prevention strategies, to make a substantial impact on the global non‐communicable diseases. There are many factors that have effects on PSD. The severity of stroke is an important factor in the occurrence of PSD. Mental history is a possible predictor of PSD. Prevention of PSD requires social and family participation, and holistic therapy approach.RECOMMENDATIONSThe recommendations listed below must be considered.

For any successful outcome in treating PSD, nursing, social worker, family members, and power of attorney or guardians should team up for better living arrangement, because this study showed that patients living with others have better outcomes than those living alone.
Social determinant factors cannot be ignored in this patient population. Considering social determinant factors such as level of poverty, less than high school education, median house income, employment, transportation factors all play a role for successful outcome in managing PSD.
Support or Funding InformationEinstein Institute ‐ USATThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Identification of Actionable Genomic Alterations in Tissue Using Idylla™
Authors: McKillip Kelsey Dillehay , Koch Matthew , Hodges Kurt 
Published: June 2021

Quick and reliable identification of actionable genomic alterations is essential to providing high‐quality cancer care. Herein we describe our assessment of Idylla™, a fully automated, cartridge‐based, PCR system for the qualitative detection of actionable genomic alterations in formalin‐fixed, paraffin‐embedded (FFPE) tissue. Three different Idylla™ assays were evaluated to demonstrate the system's ease of use, concordance with established methodology, and overall clinical utility.Thirty‐six patient samples, previously characterized using a clinically validated method, were assessed for EGFR mutations, BRAF mutations, or microsatellite instability (MSI) using Idylla™. The Idylla™ MSI Mutation Assay, which detects mutations in seven novel, tumor specific MSI loci (ACVR2A, BTBD7, DIDO1, MRE11, RYR3, SEC31A, and SULF2), was used to assess microsatellite stability in twelve cases of colorectal cancer. The Idylla™ EFGR Mutation Assay, which detects 51 mutations in exons 18, 19, 20, and 21 of the EGFR gene, was used to identify mutations in twelve cases of lung cancer. Lastly, the Idylla™ BRAF Mutation Assay, which detects seven mutations in codon 600 of the BRAF oncogene, was used to detect mutations in twelve cases of melanoma.Briefly, one 10μm FFPE tissue section was loaded into the cartridge per the manufacturer's instructions. No manual macrodissection was performed. A representative H&E stained slide was retrospectively reviewed and scored for neoplastic cell content by a Pathologist (K.H.). Idylla™ assay results were compared to previously reported results. Three cases, one per assay, were excluded from the final analysis due to lack of neoplastic cell content (NT = no tumor) or assay incompatibility.Overall, the adjusted concordance between the Idylla™ assays and clinically validated methodologies was high. The Idylla™ MSI Mutation Assay was 100% (11/11) concordant with the immunohistochemical assay for mismatch repair (MMR), which included markers MLH1, MSH2, MSH6, and PMS2. The Idylla™ EGFR and Idylla™ BRAF Mutation assays were 91% (10/11) concordant with Sanger sequencing results. Additional studies utilizing a third methodology are needed to further evaluate discordant results.The Idylla™ assays showed high concordance with previously reported results generated using clinically validated methods. Advantages of the Idylla™ system include minimal hands‐on time and rapid turnaround time. In conclusion, Idylla™ offers fast and reliable analysis for a variety of actionable genomic alterations in FFPE tissue.Support or Funding InformationSupport for this project was provided by the Department of Pathology and Laboratory Medicine.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
A New Series of Gs‐ and β‐Arrestin‐biased β2‐Adrenoceptor Agonists
Authors: Woo Anthony Yiu‐Ho , Ge Xinyue , Pan Li , Xing Gang , Mo Yongmei , Xing Ruijuan , Li Xiaoran , Zhang Yuyang , Wainer Irving W. , Cheng Maosheng , Xiao Rui‐Ping 
Published: June 2021

β‐Arrestins are implicated in desensitization of activated G protein‐coupled receptors (GPCRs) and transduction of signals in their own right. Biased ligands possessing different efficacies in activating different G protein‐dependent and β‐arrestin‐dependent signals downstream of a single GPCR have been described. Here, we report the characterization of agonist bias for compounds developed along a drug discovery project of β2‐adrenoceptor agonists. Compounds, including derivatives of fenoterol, 2‐amino‐1‐phenylethanol and 2‐amino‐2‐phenylethanol, were obtained or synthesized and their effects on cardiomyocyte contractility, cAMP synthesis and β‐arrestin recruitment were determined in β2‐adrenoceptor‐expressing cells. Gs versus β‐arrestin bias were analyzed by the operational model. Gs versus Gs/Gi bias were studied by means of sensitivity towards pertussis toxin, a Gi disruptor. Three compounds with a core structure of 5‐(1‐amino‐2‐hydroxyethyl)‐8‐hydroxyquinolin‐2(1H)‐one were identified as β‐arrestin‐biased β2‐adrenoceptor agonists. These findings would facilitate the development of novel drugs for the treatment of heart failure and asthma.Support or Funding InformationThis work was supported by the Ministry of Science and Technology of the People's Republic of China under the National Key Research and Development Program of China [2018YFA0507603], the National Science and Technology Major Project [2013ZX09507001‐001002, 2013ZX09301305‐001, 2013ZX09508104, 2018ZX09739009], the National Basic Research Program [2012CB518000], the National Natural Science Foundation of China [81673355, 81872752, 31521062, 81630008, 81790621], Beijing Municipal Science & Technology Commission [Z171100000417006], and the intramural research program of the NIH, USA.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Osteogenic Differentiation of Normotensive Rats Depends on the β‐adrenergic Receptor
Authors: Barreto Ayná Emanuelli Alves , Brito Victor Gustavo Balera , Ballassoni Beatriz Babeto , Frasnelli Sabrina Tfaile , Patrocinio Mariana Sousa , Santos Carlos Ferreira , Lara Vanessa Soares , de Oliveira Sandra Helena Penha 
Published: June 2021

Bone remodeling is a complex process that depends on the balance between formation and resorption bone, a process which is regulated by bone cells and systemic factors, like the Sympathetic Nervous system (SNS). The mediators of these system are able to regulate bone metabolism through adrenergic receptors on the surface of the osteoblasts. However, the role of β‐adrenergic receptors is not clear in the osteogenic differentiation process. Thus, in this study we aimed to evaluate the role of B‐adrenergic receptor on osteoblastic differentiation of bone marrow mesenchymal stem cells from normotensive and Spontaneously Hypertensive Rats (SHR).Methods70‐days‐old male Wistar and SHR rats were used for bone marrow collection from femurs, which was placed in cell culture flasks and after in to 24‐well plates, where they received osteogenic medium (OM: MEM, plus 50 μg/mL ascorbic acid, 10 mM β glycerophosphate, and 10−8 M dexamethasone) and the treatment with Carvedilol (1μM), non‐selective adrenergic receptor antagonist, or Nebivolol (0,1 μM), β1‐adrenergic receptor antagonist. Cell proliferation (MTT assay) and alkaline phosphatase specific activity (Alp) were analyzed at day 7, 10 and 14. Mineralization was evaluated at day 14, by Alizarin Red S. Gene expression of osteogenic markers and B1 and B2‐adrenergic receptor were evaluated at day 7, by real time‐RT‐PCR. The proteolytic activity of matrix metalloproteinase 2 and 9 (MMP‐2 and MMP‐9) were evaluated at day 7 using gelatin zymography. The protocol was approved by Institutional Animal Care and Use Committees (School of Dentistry of Araçatuba; Process 00686‐2016).ResultsAlp activity increased in OM group from Wistar rats at day 7 and the Nebivolol group reduced those activity at day 7 and at day 10. SHR OM group did not present Alp increase, and the treatment with both drugs did not change it. Nebivolol treatment decreased Runx2, Osterix and β‐catenin in Wistar compared to OM. In SHR, only Osterix was reduced. Alp, Osteocalcin and Bone sialoprotein have significative decrease in cells from Wistar treated with Nebivolol compared to OM. Pro and active MMP‐2 was reduced by Nebivolol treatment just at Wistar cells. Besides that, Nebivolol reduced Adrb1 gene expression at day 7 in Wistar group compared to OM. Mineralization showed that Nebivolol reduced mineral deposition in Wistar compared to OM.Conclusionβ1 adrenergic receptor seems to be involved in the osteogenic differentiation of cells from Wistar rats.Support or Funding InformationFAPESP (Grant: #2015/03965‐2) and CAPES.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Mast Cell Supernatant Inhibit Bone Formation Markers Gene Expression
Authors: Frasnelli Sabrina Cruz Tfaile , Jordão José VR , Linjardi Maria Carolina , Balassoni Beatriz B , Brito Victor Gustavo B , Barreto Ayna E A , Lara Vanessa S , Santos Carlos F , Oliveira Sandra HP 
Published: June 2021

Spontaneously hypertensive rats (SHR) present genetic alterations in bone metabolism and in adaptive immunity. Mast cells (MCs) play a fundamental role in inflammatory response, tissue repair and defense of the organism and may also be involved in the bone metabolism. Thus, in this study we aimed to evaluate the influence of mast cell mediators in the acquisition of the osteogenic phenotype in vitro and in the gene expression of bone markers from calvariae cells of SHR.MethodsPrimary culture from neonatal calvariae obtained by explant technique were expanded and plated in 24‐well culture plates where they received osteogenic medium (OM, ascorbic acid, β‐glycerophosphate and dexamethasone). The RBL‐2H3 MC lines were adapted to osteogenic medium, subsequently stimulated via FcɛRI, and culture supernatant was collected and was added directly into the calvariae culture in concentration of 15%, 10% and 5%. Cell viability was accessed by MTT assay, and gene expression of osteogenic markers was evaluated at day 7 by qRT‐PCR. The protocol was approved by Institutional Animal Care and Use Committees (School of Dentistry of Araçatuba; Process:00490‐2018).ResultsMTT assay did not show a cytotoxic potential from MC supernatant on calvariae culture. MC supernatant, in all concentration, significantly decreased gene expression of the transcription factors Runx2, Osterix, but not β‐catenin. Moreover, it decreased osteocalcin and bone alkaline phosphatase expression, in a dose‐dependent manner. Bone sialoprotein expression was decreased in response to the higher MC supernatant concentration, but the opposite was observed in response to the lower concentration. Osteopontin and type 1 collagen expression were decreased, in a similar manner by all MC supernatant concentrations.ConclusionOur current data allow us to suggest that MC‐derived factors can directly inhibit bone formation‐related markers expression. Further studies are being performed to better understand the mechanisms related to mast cell – bone cell crosstalk.Support or Funding InformationFinancial support and acknowledgments: FAPESP (Grant: #2015/03965‐2 and Grant: #2017/05873‐3)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Inhibition of Autophagy in Cardiomyocytes by Calmodulin Antagonists
Authors: Lopez Vanessa , Hayden Matt , Giles Jennifer , Keomanivong Faithe , Wauson Eric M , Tran Quang‐Kim 
Published: June 2021

Macroautophagy (hereafter referred to as autophagy) is a catabolic process that regulates important aspects of myocardial metabolism. While numerous studies have indicated involvement of signaling via Ca2+ in autophagic flux, the precise mechanisms remain unknown. Calmodulin (CaM) is a ubiquitous transducer of intracellular Ca2+ signals by interacting with an estimated network of 300 cellular proteins. We have begun to examine the role of CaM in autophagic flux in cardiomyocytes. A basal level of autophagy is required for normal myocardial function. Chloroquine dose‐dependently reduces basal autophagic flux in H9c2 cardiomyocytes, as indicated by LC3 immunoblotting, p62 immunofluorescence, and autophagic flux assays. Competitive binding assays using purified CaM and FRET‐based CaM biosensors demonstrate direct Ca2+‐dependent CaM binding to chloroquine. The structurally distinct CaM antagonists W‐7, trifluoperazine, and CGS 9343B also dose‐dependently inhibit basal autophagic flux by reducing autophagosome degradation. Most CaM‐dependent processes depend at the front end on the amplitude and dynamics of intracellular Ca2+ signals. Interestingly, chloroquine, W‐7, trifluoperazine, and CGS 9343b all mobilize intracellular Ca2+. The effects of these pharmacological agents to inhibit autophagic flux are thus associated with their inhibition of CaM and not of initial Ca2+ signals produced in cells. These data indicate a role for CaM in the control of autophagic flux in cardiomyocytes.Support or Funding InformationAmerican Heart Association (15SDG25090279) and Iowa Osteopathic Education and Research Funds (Eric Wauson); NIH HL112184 and DMU IOER‐090717 (Quang‐Kim Tran)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Novel Dopamine D4 Receptor‐Selective Compounds Reveal Structure‐Activity Relationships that Engender Agonist Efficacy
Authors: Keck Thomas M , Free R. Benjamin , Day Marilyn M , Fountain Griffin , Cooper Charles , Bonifazi Alessandro , Newman Amy Hauck , Sibley David R , Wu Chun , Boateng Comfort 
Published: June 2021

The dopamine D4 receptor (D4R) plays important roles in cognition, attention, and decision making. Novel D4R‐selective ligands have promise in medication development for neuropsychiatric conditions, including Alzheimer's disease and substance use disorders. To identify new D4R‐selective ligands, and to understand the molecular determinants of agonist efficacy at D4R, we report a series of eighteen novel ligands based on the classical D4R agonist A‐412997 (2‐(4‐(pyridin‐2‐yl)piperidin‐1‐yl)‐N‐(m‐tolyl)acetamide). We report a series of eighteen novel D4R ligands with varied substitutions on the phenylpiperidinyl ring, linker region, and/or the arylamide moieties. Compounds were profiled using radioligand binding displacement assays, β‐arrestin recruitment assays, cAMP inhibition assays, and molecular dynamics computational modeling. We identified several novel high‐affinity (Ki ≤ 4.3 nM) and D4R‐selective (>100‐fold vs other D2‐like receptors) compounds with diverse partial agonist and antagonist profiles, falling into three structural groups. Group 1 modifications resulted in a gain of efficacy at D2Rs and D3Rs. Group 2 modifications resulted in lower partial agonist efficacy at D4R. Group 3 modifications resulted in high‐potency full antagonists at D4R. These compounds inform receptor‐ligand interactions that control efficacy at D2‐like receptors and may provide insights to targeted drug discovery leading to new compound development and new tools for a better understanding of the role of D4Rs in neuropsychiatric disorders.Support or Funding InformationSupport for this research was provided by High Point University, Fred Wilson School of Pharmacy. Additional support was provided by the National Institute of Neurological Disorders and Stroke‐Intramural Research Program, National Institute on Drug Abuse‐Intramural Research Program (Z1A DA000609), and Rowan University.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Sporoderm‐broken spores of Ganoderma lucidum water extract (BSGLWE) inhibits high‐fat diet induced obesity through regulating gut microbiota in mice
Authors: Guo Chenjie , Sang Tingting , Guo Dandan , Li Mingyan , Li Zhenhao , Wu Kaikai , Xu Jing , Na Kun , Wang Xingya 
Published: June 2021

Obesity is a worldwide epidemic disease associated with low‐grade chronic inflammation. Recent evidence shows that intestinal dysbiosis contributes to obesity and its comorbidities. Ganoderma lucidum (G. lucidum) is a well‐known medicinal mushroom in traditional Chinese medicine with antidiabetic effect. In this study, we examined whether sporoderm‐broken spores of Ganoderma lucidum water extract (BSGLWE), mainly contains G. lucidum polysaccharides (GLPs), could regulate gut microbiota and inhibit obesity and insulin resistance. BSGLWE at different concentrations (100 mg/kg and 300 mg/kg) were individually administered to HFD‐fed mice and LFD‐fed mice for 12 weeks. We found that BSGLWE inhibit high‐fat diet (HFD) induced weight gain, visceral fat accumulation, inflammation in HFD‐fed mice. BSGLWE decreased the HFD‐induced high level of blood lipid, especially free fatty acids (FFAs) and low‐density lipoprotein (LDL) in HFD‐fed mice. In addition, BSGLWE inhibited TLR4/Myd88 signal pathway in white adipose tissues. 16S rDNA sequencing demonstrated that BSGLWE treatment significantly changed the composition of the gut microbiota in mice fed HFD. Gene expression analysis showed down‐regulation of pro‐inflammatory cytokines (TNF‐α, IL‐6, IL‐1β) in tissues and up‐regulation of tight junction proteins (occludin and ZO‐1), Muc2 and Reg3g in small intestine after BSGLWE treatment. Moreover, BSGLWE also reversed HFD‐induced gut dysbiosis and improved the intestinal barrier functions in the HFD‐fed mice. In conclusion, our date show that the BSGLWE might be used as prebiotic agents to prevent obesity‐related metabolic disorders.Support or Funding InformationSupported by Science and Technology Planning Project of Zhejiang Province (Grant No. 2019C02100) and National Natural Science Foundation of China (Grant No. 81473397).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Physiology Understanding (PhUn) Week at Texas A&M University‐Kingsville: a Retrospective Study
Authors: Lopez Hector , Velez‐Hernandez Maria E 
Published: June 2021

Texas A&M University‐Kingsville (TAMUK) is located in Kingsville, Texas and serves a highly diverse student body of around 9,000 students. PhUn week is a K‐12 community outreach activity that in 2014 had 86 events nationwide (www.aps.org). Out of the 86 events, only three of them were in Texas, and none of them south of San Antonio. During the Fall semesters of 2016, 2017 and 2018 the Biological and Health Sciences (BHS) Department at TAMUK offered the course Understanding Human Physiology (BIOL 4355) centered on service learning. As part of this course, students developed ways to teach newly acquired physiology concepts to elementary and middle school students. Interactive workshops were presented during Physiology Understanding Week as a way to showcase what students had learned in the areas of cardiovascular, immune, respiratory, renal and nervous system. Support from the American Physiological Society, Service Learning initiatives at TAMUK, and the TAMUK BHS Department were critical for the success of this program. Here we will discuss how in 3 years, a total of 41 TAMUK undergraduate presenters and 13 volunteers impacted five schools and more than 500 elementary and middle school students. PhUn week activities allowed the university to build local partnerships between science teachers and student scientists. In addition, this kind of engaging activities served as a platform for students to reach out to our communities, and to motivate the next generation of scientists.Support or Funding InformationThis project was funded by The American Physiological Society, Texas A&M Service Learning Initiative and the TAMUK Biological and Health Sciences Department.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.