bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ascorbic Acid Content, Phenolic Compounds and Antioxidant Capacity of Brazilian Savannah Native Fruits
Authors: Naves Maria Margareth Veloso , Alves Aline Medeiros , Dias Tiago , Hassimotto Neusa Mariko Aymoto 
Published: November 2023

The Brazilian Savannah (Cerrado biome) produces several native fruits, such as cagaita (Eugenia dysenterica DC), cerrado cashew (Anacardium othonianum Rizz.) and gabiroba (Campomanesia adamantium (Cambess.) O. Berg), which are widely used as food and in folk medicine. In the present study, these fruits were investigated as potential sources of antioxidant substances. The fruits were characterized concerning the total ascorbic acid content by liquid chromatograph equipped with diode‐array detector (HPLC‐DAD), total phenolic compounds by UV/visible spectrophotometry, antioxidant capacity by three different methods (2,2‐diphenyl‐1‐picrylhydrazyl [DPPH], Ferric Reducing Antioxidant Power [FRAP], and Oxygen Radical Absorbance Capacity [ORAC]), and the flavonoids composition by HPLC‐DAD. The gabiroba presented higher contents of ascorbic acid (614.9 mg.kg−1) and total phenolics (12,225.9 mg GAE.kg−1), and greater antioxidant capacity than cagaita and cerrado cashew. Nevertheless, the three fruits showed considerable contents of bioactive compounds in relation to other Brazilian native fruits. The correlation coefficients between total ascorbic acid or total phenolic contents and antioxidant capacity were high and significant (0.970 ≤ r ≤ 0.998; P < 0.05). Quercetin derivatives were found in cagaita (19.4 mg.kg−1) and myricetin derivatives in cerrado cashew fruit (12.0 mg.kg−1). The gabiroba showed relevant catechin content (233.2 mg.kg−1). Besides, peonidin 3‐glucoside was the main anthocyanin in cerrado cashew fruit, which flavonoids composition was first identified in this study. These Brazilian native fruits may be considered as important sources of natural antioxidants and potential alternatives of bioactive compounds for food science and nutrition. The gabiroba (C. adamantium) stands out from other fruits because of its relevant content of vitamin C and of phenolic compounds, particularly catechin, and because of its high antioxidant capacity.Support or Funding InformationConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq‐Brazil) for financial support (Proc. # 485565/2012‐9) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES‐Brazil) for scholarship support.
Elasticity and Vascular Endothelial Function in Patients with Aortic Valve Insufficiency
Authors: Silveira João Vicente , Katayama Keyla Yukari , Sangaleti Carine Teles , Ferreira Janaina , Hong Valeria Costa , Lopes Heno Ferreira , Consolim‐Colombo Fernanda Marciano 
Published: November 2023

BackgroudAortic insufficiency (regurgitation) is a common valve disease in young and middle‐aged individuals, which requires from the cardiovascular system a continuous volume overload. Patients can remain asymptomatic for many years and subsequently they can present symptoms of congestive heart failure. The remodeling of the great vessels has been observed in patients with severe regurgitation. However, little is known about the changes in the elasticity of small arteries and endothelial function in a moderate condition, without clinical symptoms.AimOur goal was to assess small artery elasticity and endothelial function by peripheral arterial tonometry. The hemodynamic profile was characterized by the continuously and noninvasively analyses of the blood pressure curves.MethodsWe evaluated 41 individuals of both gender, aged 18–55 years divided into two groups: control (n = 23 healthy) and aortic regurgitation (n = 18, classified as mild to moderate through Doppler echocardiography criteria, and asymptomatic). For the acquisition and analysis of hemodynamic variables: systolic blood pressure (SBP), diastolic (DBP), heart rate (HR), end‐systolic volume (ESV), cardiac output (CO) and total peripheral resistance (TPR), the monitor Finometer® and the BeatScope software was used. The vascular elasticity and endothelial function were assessed by the EndoPAT®. Statistical analysis was performed using Student's t test, unpaired, with p <0.05, the values are presented in mean ± SEM.ResultsIndividuals with aortic regurgitation (48.5 ± 3.2 years; BMI 27.8 ± 1.4 kg/m2) compared to the control group (n = 23, 41.7 ± 1.8 years; BMI 26 4 ± 0.7 kg/m2) had the follows hemodynamic changes: increased SBP (138.6 ± 3.7 vs 126.7 ± 2.8 mmHg) ESV (151.7 ± 13.5 vs 83.9 ± 3, 0 ml) and CO (10.6 ± 1.0 vs 5.4 ± 0.2 l/min); and decreased DBP (64.7 ± 2.6 vs 75.3 ± 1.8 mmHg) and TPR (0.6 ± 0.1 vs 1.1 ± 0.1 UPR). Endothelial function was not different between groups. However, there was a significant increase in the elasticity of small arteries in the aortic regurgitation group in absolute values (20.2 ± 5.0 vs 5.7 ± 3.9%) and also for normalized values according to a HR of 75 bpm (16.9 ± 4,5 vs −2.5±3.9%).ConclusionYoung adults with asymptomatic aortic regurgitation had a higher elasticity of the small arteries and a preserved endothelial function.
Animal Models of Heart Failure: the Forgotten Animal Model
Authors: Chandrasekera Charukeshi 
Published: November 2023

Heart failure remains a leading cause of death and an economic burden worldwide. The research community continues to tackle this epidemic by dedicating extensive research efforts to delineate heart failure mechanisms and to develop novel therapeutics. Animal models form the cornerstone of these basic and translational research efforts; however, despite decades of extensive research, human heart failure remains poorly understood and only limited therapeutic measures are available to human patients. While animal models in species ranging from fruit flies to primates have considerably advanced our understanding of animal cardiovascular physiology and pathophysiology, research success from these models have not proportionally translated into therapeutic success for human patients. A growing body of human‐specific mechanistic and clinical data indicate that the translational discrepancy is primarily due to the species barrier: from gene expression to excitation‐contraction coupling to drug responses, animal models do not accurately replicate human heart failure causes, natural history, manifestations, complications, and responses to treatments. Immutable interspecies differences occur at every level of biological activity and are further confounded by biological variability (age, sex, and strain), and even differences in housing and husbandry practices as well as experimental conditions. Given the disappointing history of animal research translation for heart failure, the paucity of definitive treatments, and the emergence of heart failure as a dominant cause of morbidity and mortality in the U.S. and across the world, the need to move from animal models to human‐specific research seems evident. In fact, other researchers in the field are urging the heart failure community to “modify and enhance the currently dominant translational paradigm and provide new important directions of research.” Here we present evidence indicating why it is imperative for the heart failure research community to devise a plan to incorporate Homo sapiens as the quintessential animal model. We provide specific examples of how genetic, biochemical, physiological, anatomical, and technical limitations inherent in animal models can be overcome with similar studies in humans and present how an integrative human‐based research framework incorporating every level of human biological complexity – from nucleic acid to whole organism level and beyond – can serve as the primary platform from which basic science discoveries are launched and more effective therapeutics are tested. If the ultimate goal of the research community is to advance preventive and reparative approaches for human heart failure, we need to transition from the quest to generate “better” animal models to the prioritized, widespread use of human‐based, human‐relevant research strategies.Support or Funding InformationAuthor Institution
Cardiac compensation in ErbB2‐deficient zebrafish embryos
Authors: Fleming Nicole D , Samsa Leigh Ann , Liu Jiandong 
Published: November 2023

During heart development, the heart chambers undergo dramatic changes in chamber topology, most notably the formation of luminal, muscular protrusions called trabeculae. While altered trabeculation is associated with many congenital heart diseases, complete failure to form trabeculae results in embryonic lethality across different species. We have previously reported that ErbB2 signaling is required for cardiac trabeculation. Although erbb2 mutant hearts do not exhibit any functional defects initially, these hearts develop progressive cardiac dysfunction with reduced fractional shortening, and eventually fail. However, the mechanism underlying this functional deterioration in the absence of trabecular formation is not known. Using zebrafish as a model, we found that inhibition of ErbB2 activity pharmacologically and genetically to block cardiac trabeculation resulted in an increase in ventricular cardiomyocyte cross‐sectional area and myofibril size. This cardiac phenotype is reminiscent of hypertrophic growth of an adult heart subjected to mechanical overload. Consistently, we found that the expression of nppa, a hypertrophic marker gene, was elevated in erbb2 mutants compared to controls. In addition, inhibition of Target of Rapamycin (TOR) signaling by rapamycin treatment suppressed erbb2 mutant hypertrophic growth phenotype, suggesting that hypertrophy of erbb2 mutant hearts occurs in an mTOR‐dependent manner. Taken together, we propose that trabeculae may play a role in optimizing chamber topology for efficient cardiac function.Support or Funding InformationNational Science Foundation Graduate Research Fellowship (NSF‐GRF): DGE‐1144081
The effect of Body Mass Index on Pain Levels of Patients with Fibromyalgia
Authors: Torres‐Gutiérrez César J. , Merriwether Ericka , Rakel Barbara , Dailey Dana , Muenters Li Alemo , Abdelhamid Ramy , Darghosian Leon , Vance Carol , Crofford Leslie , Sluka Kathleen 
Published: November 2023

Fibromyalgia (FM) is a chronic pain syndrome characterized by widespread pain, depression, and mood and sleep disturbances. There is currently no consensus on the pathogenesis of FM. Overweight women are 60–70% more likely to develop fibromyalgia and experience more severe pain symptoms than normal women. Adipose cells release pro‐inflammatory cytokines (IL‐6, TNF‐α, Leptin) that are linked to pain pathogenesis. This study aims to determine the relationship between weight or body mass index (BMI) and pain in fibromyalgia. A sample of 93 women was recruited for participation in a set of tests which classify the pain felt by the participants. Pearson Product Moment Correlation (r) analyses were done between BMI and the pain levels. One‐way analysis of variance (ANOVA) was used to determine group differences in pain measures. For a sub‐analysis consisting of 27 patients, blood samples were acquired from the participants. The Peripheral Blood Mononuclear Cell layer (PBMC) was isolated. Monocyte phenotype was determined using fluorescence‐activated cell sorting (FACS) and a Pearson Product Moment Correlation (r) analysis was done. We found that there is no relationship between BMI, Pain levels and Monocyte phenotype.Support or Funding InformationThis study was supported in part by the National Institutes of Health (NIAMS) AR063381 and AR063381S1, and the Carver College of Medicine Institutional funds. We thank the FAST study team for their assistance with scheduling and data collection.
Multi Quantum Biophotonic Energy's Ability to Reduce Fear Response and Anxiety in Williams Syndrome (case study)
Authors: Cohen Jay , Einstein George , Tulp Orion L 
Published: November 2023

Due to the deletion of multiple genes on the long arm of chromosome 7, individuals with Williams Syndrome often elicit a hyperactive response to nonsocial frightening stimuli. The objective of this research was to determine if Multi Quantum Intravenous UVC/UVA light energy and subsequent NIR were effective in reducing the anxieties and fear responses associated with these stimuli. Our study involved a 17 year‐old female with Williams Syndrome who expressed distress when exposed to the sounds of laughter. We determined the particular sounds and associated frequencies that evoked anxiety and a fear response with this individual. These sounds were recorded and when reproduced elicited a consistent and predictable hyperactive response from this individual. Cognitive Behavioral Therapy, CBT, alone did not significantly reduce the hyperactive response recorded.This individual received Multi Quantum Intravenous UVC/UVA energy followed by Quantum NIR. The amount of energy induced was calculated for a 36.28Kg individual.This treatment was administered once daily over a 4 day period. The individual was then exposed to the same recordings that previously elicited a hyperactive response. Subsequent responses were noted to be diminished and less consistent for several days following the Multi Quantum Biophotonics treatment. (MBPT). Observational data from this study suggested that MBPT can help modulate the limbic’ system's fear response that is initiated in individuals with Williams Syndrome.Further investigational research involving EEG studies combined with the Avtandil Anuashvili method identifying specific brain functions with Williams Syndrome individuals is indicated.
How the γPKC activity is regulated in neurodegenerative spinocerebellar ataxia type 14 (SCA14)
Authors: Aslam Naveed , Alvi Farah 
Published: November 2023

The neurodegenerative spinocerebellar ataxia type 14 (SCA14) is linked with slowly progressive cerebellar ataxia accompanied by abnormal eye movements and slow slurred speech. The ataxic symptoms are due to loss of purkinje cells leading to cerebellar neurodegeneration. Recent observations directly link γPKC with SCA14 and its gene PRKCG is now widely recognized as a disease causing gene. γPKC is specifically expressed in brain and is highly expressed in purkinje cells. The SCA14 disease is characterized by degeneration of purkinje cells. Experimental observations indicate that γPKC can modulate the morphology and behavior of purkinje cells. Both positive and negative regulation of γPKC can be linked with changes in size and complexity of dendritic arbor in purkinje cells. Here, we investigate the question that how the activity of γPKC is regulated in purkinje cells of cerebellum? The growth of dendritic structure is strongly inhibited by γPKC activation. Here, we examine a proposal that γPKC activity in purkinje cells can be regulated through a DAG‐mediated molecular loop between γPKC and DGKγ. Our results show that γPKC activity in purkinje cells is regulated through a net negative feedback loop. Our results imply that on purinergic receptor stimulation the γPKC is activated through a sequence of DAG‐mediated molecular events. However, the γPKC restricts its own activation through a net negative feedback loop. Through our approach we are able to clarify the mechanism behind the spatiotemporal interaction of DAG effector molecules i.e. γPKC and DGKγ.Support or Funding InformationBioSystOmics
The Antioxidant Effects of Thymoquinone in Lipopolysaccharide (LPS)/Interferon Gamma (IFNg) Activated BV2 Murine Microglia Cells
Authors: Cobourne‐Duval Makini K , Taka Equar , Soliman Karam F. 
Published: November 2023

Chronic activation of microglia, the resident macrophages of the central nervous system (CNS), is implicated in the pathogenesis and progression of neurodegenerative disorders such as Alzheimer's disease. Disproportionate microglial activation drives a vicious self‐perpetuating neurodegenerative cycle via the excessive release of reactive oxygen species and pro‐inflammatory cytokines in the system. We explored the antioxidant effects of thymoquinone (TQ), a major bioactive component of Nigella sativa seed oil, in microglial activation. We hypothesized that the antioxidant properties of TQ are mediated in part by reducing the expression of proteins involved in microglia‐derived oxidative stress and modulating the activity of antioxidant enzymes. In this study, BV2 cells were stimulated with E. coli lipopolysaccharide (LPS) & interferon gamma (IFNg) in the presence or absence of TQ. To profile the effect of TQ on the global protein expression of BV2 microglial cells, two‐dimensional (2D)‐gel electrophoresis with MALDI‐TOF/TOF (matrix‐assisted laser desorption/ionization – time of flight) analysis was employed. Additionally, we assessed TQ's effect on microglial production of superoxide and nitric oxide, superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) enzyme activities and as well as the ratios of oxidized:reduced glutathione (GSSG:GSH) indicative of overall oxidative stress levels. The results obtained indicate that TQ caused changes in the expression of 60 kDa heat shock protein in LPS/IFNg stimulated BV2 cells as well as significantly (p<0.001) decreased the production of superoxide and nitric oxide and significantly (p<0.0001) decreased the levels of oxidative stress. TQ also modulated the activities of the antioxidant enzymes demonstrating increased antioxidant capacity. These findings suggest that TQ may be useful in delaying the onset or progression of neurodegenerative disorders involving chronic activation of microglia and the resultant excessive oxidative stress in the CNS. Thus, intervention of microglial activation process could be a promising therapeutic target for the treatment of a number of neurodegenerative conditions.Support or Funding InformationNIH Grants : NIMHD G12 MD007582 and P20 MD006738
FACT: Functional Analysis Clustering Toolbox for visualizing disease progression
Authors: Yang Ruoting , Watson Daniel , Hammamieh Rasha , Jett Marti 
Published: November 2023

In recent years, many studies collected temporal gene expression profiles based on DNA microarray technology for predicting the disease progression or host response to an external stress. Monitoring the functional changes, time dependency and noise is crucial to be able to dissect gene patterns. The popular computational packages for time‐series clustering usually combine several traditional clustering methods; however, these methods are not designed for time‐series and neglect the temporal information. This approach is precise and easy to apply, but it is sensitive to noise. As a result, we developed a novel computational tool ‐ FACT (Functional Analysis Clustering Toolbox) ‐ to identify the major gene patterns, visualize and compare pathways, and track functional progression. FACT can dissect spike patterns over time, provide the underlying biological functions for these spikes, and link them into a network.To illustrate the effectiveness of FACT, we applied it to eight Prion disease datasets of global gene expression in the brains of eight distinct mouse strain ‐ prion strain combinations throughout the progression of the disease. We identified the major response timeline for the prion infection for each mouse‐prion strain. Several important pathways, such as the complement pathway, showing strain‐ and time‐ specific changes, have been teased out and compared to the original paper. We identified the major responsive pathways; the complement pathway was upregulated after week 12, and the response of the complement pathway was negatively correlated with active prion levels, consistent with the incubation time.In conclusion, FACT provides a new rich, robust resource for diagnostic biomarker and therapeutic target discovery. This application to prion datasets illustrates its powerful capacity for dissecting time‐ and strain‐specific responsive genes and pathways and uncovering both the common functional progression and the unique functions for certain strains.Support or Funding InformationDISCLAIMERS: Research was conducted in compliance with the Animal Welfare Act and all other Federal Requirements. The views expressed are those of the authors and do not constitute endorsement by the U.S. Army.
THE PROTEIN KINASE Cβ INHIBITOR, ENZASTAURIN, DECREASES AMPHETAMINE‐MEDIATED BEHAVIORS IN RATS
Authors: Altshuler Rachel , Gnegy Margaret , Jutkiewicz Emily 
Published: November 2023

Amphetamines elicit their motivating effects by increasing extracellular dopamine levels in the brain. Extracellular dopamine levels are regulated by the dopamine transporter (DAT), a transmembrane protein that transports dopamine from the extracellular space into the cell. Amphetamines are taken up by DAT and reverse the transporter to release dopamine into the synapse. One protein that has been shown to be important for the mechanism of amphetamine's action is protein kinase C β (PKCβ). The inhibition of PKCβ reduces amphetamine‐stimulated dopamine efflux through DAT in vitro and in vivo while having no effect on dopamine uptake. While the effects of PKC inhibitors on amphetamine‐stimulated dopamine efflux have been characterized, it is important to understand the effects of PKCβ inhibition on amphetamine‐stimulated behaviors. The goal of this study was to determine whether inhibition of PKCβ will decrease amphetamine‐stimulated locomotion and amphetamine self‐administration. For all experiments, the selective PKCβ inhibitor enzastaurin was administered to male Sprague‐Dawley rats by intracerebroventricular (i.c.v.) injection 18 hours prior to evaluating amphetamine‐mediated behaviors. Locomotor activity was measured in infrared beam break boxes following administration of a single dose (1 mg/kg) or cumulative doses (0.32–5.6 mg/kg) of amphetamine. In self‐administration studies under a fixed ratio 5 (FR5) schedule of reinforcement, rats earned infusions of amphetamine (0.032 mg/kg/infusion) or sucrose pellets in 60‐ or 20‐min daily sessions, respectively. Pretreatment with enzastaurin reduced amphetamine‐stimulated locomotion at lower amphetamine doses (0.32 and 1 mg/kg), but this effect was surmounted by larger doses (≥ 3.2 mg/kg) of amphetamine, demonstrating a rightward shift in the amphetamine dose effect curve for locomotion. In amphetamine self‐administration studies, enzastaurin decreased the number of amphetamine infusions by over 60%. This effect was specific for amphetamine because enzastaurin did not alter the number of sucrose pellets earned. This study demonstrated that PKCβ inhibition attenuated amphetamine mediated behaviors, likely in a surmountable fashion. PKCβ inhibitors may be useful therapeutic targets for decreasing amphetamine use and abuse without altering natural rewards. Future work will investigate the mechanisms by which PKCβ inhibition alters amphetamine‐stimulated behaviors.Support or Funding InformationFunded by DA11697 and T32‐GM007767.