bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prolonged Access to Cocaine Results in Distinct Epigenetic Changes in the Prefrontal Cortex (LB622)
Authors: Ploense Kyle , Carr Amanda , Baker‐Andresen Danay , Li Xiang , Woodward Nick , Sun Yi , Bredy Timothy , Kippin Tod 
Published: June 2021

DNA methylation is a key determinant of gene expression and is implicated in neuroplasticity relevant to addiction. Here, we examine DNA methylation and mRNA expression for two genes, Homer2 and NPAS4, within the dorsal medial prefrontal cortex (dmPFC) following saline, short‐access (1h), or prolonged‐access (6h), to cocaine during self‐administration. As reported previously, only 6h rats exhibited escalated cocaine intake across sessions. Initial MeDIP‐CHIP analyses of dmPFC tissue by ChIPMonk software revealed dramatic and extremely gene‐specific changes in DNA methylation/demethylation within promoter regions and flanking the transcription start site (TSS). The Homer2 and NPAS4 promoters showed active changes in DNA methylation following 6h and 1h cocaine self‐administration compared to saline. A follow‐up analysis, via sodium bisulphite conversion followed by mass spectrophotometry interrogating a 1000bp sequence of the Homer2 promoter, confirmed increased methylation of CpG7 in the 6h rats, which contains putative consensus sequences for GATA‐1 and p300. Additionally, MeDIP followed by qPCR revealed an increase in DNA methylation for both 1h and 6h rats within the 457‐645bp upstream of the NPAS4 transcription start site (TSS).qPCR revealed an increase in Homer2 mRNA levels in the 6h versus 1h and saline conditions, and a decrease in NPAS4 mRNA in 1h and 6h versus saline conditions. These results demonstrate that prolonged cocaine self‐administration alters DNA methylation of the Homer2 and NPAS4 gene promoters within the dmPFC in a distinct manner. Additionally, the altered DNA methylation leads to decreases in NPAS4 mRNA and increases in Homer2 mRNA expression within the dmPFC. Given the known roles of Homer2 as a scaffolding protein for the metabotropic glutamate 1 and 5 (mGluR1/5) receptors and NPAS4 as a transcription factor promoting inhibitory synapse formation, these data indicate that excessive cocaine intake induces changes in gene regulation for inhibitory and excitatory synapses. Thus, excessive cocaine intake induces a distinct change in DNA methylation which may contribute the long‐term alterations in brain function associated with addiction.Grant Funding Source: NIH R21DA027115
Baicalein exerts neuroprotective effects in 6‐hydroxydopamine induced experimental Parkisonism (LB625)
Authors: Mu Xin , Lu Yang , Du Guanhua 
Published: June 2021

Baicalein, a flavonoid with potent antioxidant and anti‐inflammatory properties, has been shown to have neuroprotective effects. But baicalein has a pool dissolvability and scarcely dissolve in water. Thus,our topic group studied the crystal form of the chemical composition of baicalein. The result showed that baicalein possessed polymorphism. Moreover, β crystal form of baicalein was determined to be a superiority drug crystal because of its dominant position in stability and absorbance by constancy and biological test. So β crystal form of baicalein was used in this experiment. In rats, the behavioral and immunohistochemical manifestations after unilateral 6‐OHDA lesion were determined. Baicalein could significantly attenuate muscle tremor of 6‐OHDA lesioned rats (the burst frequency and amplitude are 13.43%, 35.18% compared to 6‐OHDA group), but could not reduce apomorphine (APO)‐induced rotations. Moreover, baicalein treatment could also increase tyrosine hydroxylase (TH)‐positive neurons (265.52% compared to 6‐OHDA group) and ameliorate the severe increase of glial fibrillary acidic protein (GFAP) immunoreactivity (70.23% compared to 6‐OHDA group) in the substantia nigra. Therefore, baicalein can be a promising candidate for prevention or treatment of Parkinson’s disease, owing to its anti‐apoptotic, pro‐differentiation and anti‐inflammatory action.Grant Funding Source: This work was supported by the Research Special Fund for Public Welfare Industry of Health (No. 200802041) and National Significant Projects of New Drugs Creation (No. 2009ZM09501‐021).
MNG promotes neurogenesis against cerebral ischemic injury (LB626)
Authors: Wang Wen , Sun Fang‐ling , Ai Hou‐xi , Zhang Li 
Published: June 2021

MNG is an active component of sarcocarp of C. officinalis that have shown neuroprotective effects. The aim of the present study is to test whether MNG promote neurogenesis via Wnt/β‐catenin signaling pathway for brain recovery in a rat model of focal cerebral ischemia. MNG were administered intragastrically once daily at the concentrations of 30, 90 and 270 mg/kg respectively for 7 days post‐ischemia. Ludmila Belayev score tests was performed to detect neurological function. Immunofluorescence staining of Nestin was used to identify the endogenous neural stem cells proliferation in the subventricular zone. The expression of proteins involved in and related to Wnt/β‐catenin signaling pathway was detected by western blotting analysis. MNG significantly promoted neurogenesis for brain recovery 7 days post ischemia. Increased expression of Wnt 3a and β‐catenin, along with activation of downstream transcription factors, indicated that the neurorestorative effects of MNG may be associated with Wnt/β‐catenin signaling pathway. These data provide support for understanding the mechanisms of MNG in neurorestorative effects and suggest a potential new strategy for stroke treatment.Grant Funding Source: Supported by the National Science and Technology Major Project 2012ZX09102201‐106.
Oral toxicity of a lectin‐protease inhibitor fraction from Tepary bean (Phaseolus acutifolius) in rats (LB632)
Authors: Noriega‐Girón Héctor , Andrade‐Portillo Verónica , López‐Martínez Francisco , Moreno‐Celis Ulisses , Blanco‐Labra Alejandro , Garcia‐Gasca Teresa , Ferriz‐Martínez Roberto 
Published: June 2021

Our previous studies showed that a lectin fraction from Tepary bean exhibits low toxicity but antinutritional effects in rats. The aim of this study was to determine the in vivo effect of a lectin‐protease inhibitor fraction (LIP‐60). Three administration schedules were tested for intragastric administered LIP‐60 in Sprague Dawley rats: 1) acute toxicity was determined using a single dose of LIP‐60 per group (10, 100, 1000 mg/body weight kg), 2) for the subchronic toxicity a daily LIP‐60 dose (100 mg/body weight kg) was administered for 28 days, 3) for the long‐term scheme, LIP‐60 (100 mg/body weight kg) was administered twice a week for 6 weeks. The animals were sacrificed to obtain blood samples in order to determine markers for renal, hepatic and pancreatic damage and also the nutritional status. Acute toxicity did not show adverse effects, only the highest dose provoked lethargy for the first 12 h. Subchronic test showed piloerection, yellow hair pigmentation, diarrhea, abdominal distention, irritability, partial food intake decrease and stationary body weight gain with a 10% decrement, blood markers for toxicity or nutritional status did not show significant alterations. The long‐term scheme did not show adverse effects neither before sacrifice nor blood markers. Our results suggest that LIP‐60 present a low toxicological profile, further studies will focus on effects on gastrointestinal tract and against colon cancer.Founding: CONACYT FOMIX (QRO‐2011‐C02‐175340)
Protective effects of dipotassium glycyrrhizinate against snake venom muscle damage (LB633)
Authors: Ziegler Jussara , Gracia Marta , de Oliveira Thais , Nascimento Laís , Rocha Thalita 
Published: June 2021

Myonecrosis is a serious consequence of Bothrops snake bites that may be due to destabilization and rupture of sarcolemma and organelles, inflammation, leading to permanent loss of muscle. Antivenom has been ineffective to neutralize this tissue damage and plant extracts have being studied as an associative therapy. In this research we analyzed the protective effect of Dipotassium Glycyrrhizinate (DPG) against myotoxic effects of Bothrops jararacussu snake venom using in vivo experimental protocols. DPG, isolated from Glicirriza glabra, is an anti‐inflammatory agent employed in treating dermatitis. The myotoxic process was followed in male Swiss mice gastrocnemius muscle at early (3 hours), intermediate (24 hours), late (3‐7 days) and final (21 days) phases after intramuscular injection of B. jararacussu snake venom (100µg/µL), followed by 2% DPG injection 30 minutes later. Control muscles were injected with DPG only. Muscles sections (10µm) were processed for light microscopy and immunohistochemistry for TNFα, IFNγ, myoD and miogenin. At early and intermediate phases, the muscle damage was characterized by delta lesions, densely‐clumped myofibrils and empty‐looking sarcoplasmic areas, inflammatory infiltrate and intense TNFα and IFNγ expression. Satellite cells and myoblasts, followed by myotubes were observed, from late to final phases, by myoD and miogenin expression. Cytokines expression coincided with the intense muscle proteolysis caused by the venom and the climax of regeneration, whereas cytokines decline, corresponded to periods of tissue remodeling and intense myofibril synthesis. The results show that DPG was able to decrease the myotoxic effects of this venom by inducing the inflammatory response and muscle regeneration.Grant Funding Source: Supported by FAPESP 2013/10163‐4
Tissue effect of lens at leukergy of patients who received low doses of ionizing radiation (LB635)
Authors: Eltokova Manshuk , Kazymbet Polat , Bakhtin Meirat , Hoshi Masaharu , Altaeva Nursulu 
Published: June 2021

Background |Aims: to explore the possibility to use the lens in the extract as a stimulant in vitro by the stimulated leukergy reaction at the liquidators of the Chernobyl Nuclear Power Plant (CNPP) with cataracts in the long term.Materials and Methods: the response of white blood cells in the presence of agglomeration of lens antigen in vitro in 60 men ‐ the liquidators of the Chernobyl accident, at the age of 42 to 65 years old, with a cataract. The average radiation dose from 3.25 ± 0.31 to 18.2 ± 0.58 cGy. Comparison group was consisted of 60 men with cataracts, the identical age, who had no exposure to ionizing radiation. The control group was consisted of 60 men, aged from 42 to 58 years old without lens pathology.Results: leukergy index of 1.03 ± 0.05% is referent at leukocyte stimulation by lens extract in the control group . The phenomenon of stimulated leukergy was identified in individuals exposed to ionizing radiation at a dose of 18,2 ± 0,58cGy., and ranged from 5.7% to 8.05% (p ˂ 0.001). This supposes a continued high autoaggression to the lens antigens and the strength of cell‐mediated immunity.Conclusion: the proposed method of leukergy in the presence of lens antigens in vitro is quite informative and resource useful for the empowerment of the differential diagnosis of cataract of radiation genesis.
Fetal Biometry of Pregnant Women in Khartoum State, Central Sudan (LB64)
Authors: Mokhtar Ahmed , Mustafa Wegdan , Ali Qurashi 
Published: June 2021

Introduction: Ultrasonic measurement of fetal Femur Length (FL) and Bi‐Partial Diameter (BPL) is a precise tool for estimation of fetal growth and development. Accurate estimation of gestational age is vital for efficient obstetric planning and for detection of fetal malformation.Objectives: Assist to construct new reference charts and equations for fetal biometry in ethnic Sudanese population, and to compare them with existing references from different international populations.Methods: This was a cross sectional study done in Khartoum ‐ Sudan involving 256 of healthy pregnant women aged between 18‐40 years that were examined by ultrasound for FL and BPL. Women selected were with singleton pregnancy in the third trimester (30‐40 weeks). Regression models were used to estimate the mean and standard deviation of both the FL and the BPD at each gestational age.Results: The results demonstrate a linear relationship between the FL and BPD measurements and the gestational age throughout the third trimester (P<0.001). The mean BPD values of Sudanese fetuses measured between 30 to 40 weeks showed that they are lower than the mean BPD values of Caucasian fetuses measured during the same period. The mean of FL measured between 30 to 40 weeks of Sudanese fetuses was higher when compared to Chinese and Singaporean fetuses, but was not significantly different when compared to fetuses from European countries.
Increased NO‐synthase activity and beneficial effect of PDE‐5 inhibition by sildenafil in pulmonary hypertension caused by pulmonary embolism (LB646)
Authors: Mizera Roman , Hodyc Daniel , Herget Jan 
Published: June 2021

Background Two mechanisms that contribute to pulmonary hypertension after acute pulmonary embolism (PE) are vascular obstruction and vasoconstriction. Vasoconstriction is influenced by NO release. We focused on NO synthase activity, production of NO oxidative products (NOx) and effect of phosphodiesterase‐5 (PDE‐5) blockade by sildenafil on pulmonary hypertension after PE.Methods Using the model of in vivo pulmonary embolism we measured changes of perfusion pressure in isolated rat lungs after blockade of NO‐synthase by L‐NAME and of PDE‐5 by Sildenafil. The NOx concentration was measured before and after PE in venous blood.Results The increase in pulmonary perfusion pressure after L‐NAME administration was higher in rats after PE. NOx plasma concentration was higher after PE than before. Perfusion pressure after PE in rats treated with sildenafil was lower (12.9 ± 0,79 mmHg) than after PE in control group (21.4 ± 3,20 mmHg).Conclusion Experimental PE in rats increases NO‐synthase activity and production of NOx. Administration of sildenafil inhibits pulmonary hypertension after PE. Our study indicates that similarly as in other forms of pulmonary hypertension sildenafil may be beneficial in the treatment of acute pulmonary embolism.Grant Funding Source: Supported by GAUK n. 634112/2012
Characterization of conserved noncoding regulatory regions by flow cytometric analysis (LB66)
Authors: Brown Amber , Pira Charmaine , Howard Kristy , Oberg Kerby 
Published: June 2021

Spatial and temporal regulation of developmental gene transcription often involves regulatory sequences found in noncoding DNA separate from the gene’s promoter. Conservation of a noncoding region (CNR) across divergent species may indicate a regulatory region critical to basic morphogenesis. CNR‐green fluorescent protein (GFP) constructs can demonstrate spatial and temporal activity; however, characterization of regulatory modules within a CNR requires quantitative, in addition to qualitative, analysis. Here we describe a novel application of flow cytometry in the characterization of CNRs.CNR‐reporter constructs were generated using a limb‐specific Shh regulatory region (LSSRR) linked to a minimal HSV‐tk driven GFP. CNR‐reporter constructs were co‐electroporated with β‐actin driven red fluorescent protein (RFP) into the presumptive limb of chicks. Adequately transfected limbs were analyzed using the 7‐Color MACSQuant Analyzer and FlowJo software to evaluate changes in CNR activity. Data was normalized to nontransfected limbs.Limbs electroporated with the β‐actin driven construct demonstrated transfection in 65.1% ± 7.9 of cells. Electroporation of the basal HSV‐tk‐GFP construct produced minimal fluorescence (relatively intensity 0.1 ± 0.04) in a small subset of cells (14.2% ± 4.4). Limbs electroporated with LSSRR‐GFP construct demonstrated robust activity in 29.8%± 6.0 of cells, with a relative intensity of 1.2 ± 0.2. A restriction enzyme generated LSSRR fragment showed intermediate activity (relative intensity 1.0 ± 0.2) in 20% ± 8.2 of cells.Our data indicate that flow cytometric analysis can identify changes in the distribution and intensity of CNR activity, which enhances our ability to characterize CNR‐related regulatory sequences.
Isometric handgrip (IHG) training‐induced reductions in resting blood pressure: reactivity to a 2‐minute handgrip task identifies responders and non‐responders in young normotensive individuals (LB661)
Authors: Somani Yasina , Hanik Sarah‐Anne , Malandruccalo Amanda , Freeman Shane , Caruana Nic , Badrov Mark , Baross Anthony , Swaine Ian , Milne Kevin , McGowan Cheri 
Published: June 2021

In people with hypertension, systolic blood pressure (SBP) reactivity to an isometric handgrip task (IHGT), but not a cold pressure task (CPT), is predictive of IHG training‐induced reductions in resting SBP. To investigate whether these findings could be extended to include young normotensives, resting BP and BP reactivity to an IHGT (2‐minute sustained contraction at 30% maximal voluntary contraction, MVC) and a CPT (2‐minute hand immersion in a cold water bath) were measured prior to and following 10 weeks of IHG training (4, 2‐minute IHG contractions at 30% MVC, using alternating hands, interspersed with 1‐minute rest periods, 3X/week) in 7 normotensive individuals (3 females, 4 males; age=25 ± 5.7 years). BP reactivity was derived by calculating the difference between peak stress BP and mean baseline resting BP. Significant training‐induced reductions in resting SBP (p<0.001) were strongly correlated with pre‐training SBP reactivity to the IHGT (r=‐0.8, p=0.03), but not the CPT (r= 0.2, p=0.6). These preliminary findings suggest that SBP reactivity to a short and simple handgrip task can be used as a predictive tool to identify who will respond best to IHG training. It might be possible to further explore how the IHG training stimulus could be optimized in non‐responders, to ensure that they too, experience reductions in resting BP.Grant Funding Source: Supported by University of Windsor Kinesiology seed grant
Heart rate variablity indices are poor predictors of exercise capacity in healthy type 1 diabetics (LB664)
Authors: Peebles Karen , Baldi J, Chris , Hoye Neil , Murray Angus , Sheat Catherine , Williams Michael , Wilson Genevieve , Wilson Luke 
Published: June 2021

People with diabetes often have chronotropic incompetence and reduced exercise tolerance. Chronotropic incompetence has been associated with autonomic dysfunction, thus we determined the ability of resting heart rate variability (HRV) to predict an altered exercise response in healthy individuals with type 1 diabetes (T1D). Baseline measures were taken followed by quantification of HRV with power spectral analysis during controlled breathing (15 breaths·min‐1) in 20 T1D (10 male & 10 female) screened for ischaemic cardiac disease and 12 age‐, weight‐, and training‐matched non‐diabetics (CON: 7 male & 5 female). These measurements were followed by a VO2max test (with ECG). Resting HR (73 ± 10 vs. 64 ± 10 beats·min‐1; P = 0.01) was higher and mean arterial blood pressure (92 ± 12 vs. 90 ± 11 mm Hg; P = 0.68) was not different between T1D and CON respectively. HR reserve (104 ± 17 vs. 121 ± 11 beats·min‐1; P < 0.001), VO2max (31 ± 9 vs. 41 ± 9 mL·min‐1·Kg‐1; P =0.005), HRV total power (1317 ± 1146 vs. 7493 ± 15080 ms2; P = 0.024), and HRV high frequency power (441 ± 491 vs. 3840 ± 9883 ms2; P = 0.029) were lower in T1D vs. CON respectively. Absolute max HR (177 ± 15 vs. 185 ± 10 beats·min‐1; P = 0.09), % of age predicted max HR (95 ± 6 vs. 97 ± 2 %; P = 0.07), and HRV low frequency power (328 ± 279 vs. 1672 ± 3433 ms2; P = 0.09) were not different in T1D vs. CON respectively. Despite group differences in HRV, linear correlations showed that resting HRV total, high frequency, and low frequency power accounted for < 20% of the variability in resting HR, HR reserve, max HR, and VO2max in T1D. Resting HRV indices are poor predictors of cardiovascular exercise response in healthy T1D.Grant Funding Source: Supported by Anderson's trust
Vascular dysfunction induced by organ culture is dependent of male sex hormones (LB677)
Authors: Andres Monica , Flynn Daniel , Abdu Semah , Gomez Juan , Portilla María , de Bethencourt Fermin , Ferrer Mercedes 
Published: June 2021

Androgens exert beneficial effects on vascular function by regulating the release and function of NO, prostanoids and reactive oxygen species. Since organ culture induces phenotypic changes in endothelial cells similar to those observed in some cardiovascular diseases, the aim of this study was to analyze the preventive role of male sex hormones on the vascular damage induced by organ culture. We used aortic segments from control and orchidectomized rats incubated for 20 hours at 37ºC in serum free culture medium. In this system we studied: i) the prostanoids and H2O2 production in the culture medium; ii) the hyperpolarizing mechanisms on the responses induced by acetylcholine (Ach) and by the NO donor, sodium nitroprusside (SNP) and iii) the effect of TXA2‐mimetic U‐46619 on vasodilator responses. The results showed that organ culture: i) increased the production of prostanoids and H2O2 in aorta from both groups of rats; ii) decreased the Ach‐induced relaxation in aorta from orchidectomized rats, while increased that induced by SNP and iii) decreased the Ach‐ and SNP‐induced responses after incubation with U‐46619 only in orchidectomized rats. These findings suggest a preventive role of male sex hormones on organ culture‐induced vascular damage.Grant Funding Source: Supported by grants (to M. F.) from the Fondo de Investigaciones Sanitarias (PI0011406) and (to F. R. B.) from the Sociedad Española de Urología (2013‐14).
Establishment and validation of a pre‐clinical, multi‐center, multi‐species consortium for the assessment of infarct size‐reducing agents: CAESAR (Consortium for the preclinicAl assESsment of cARdioprotective therapies) (LB698)
Authors: Jones Steven , Steenbergen Charles , Lefer David , Tang Xian‐Liang , Kukreja Rakesh , Li Qianhong , Kong Maiying , Bhushan Shashi , Stowers Heather , Kondo Kazuhisa , Hunt Gregory , Goodchild Traci , Orr Adam , Chang Carlos , Ockaili Ramzi , Salloum Fadi , Guo Yiru , Bolli Roberto 
Published: June 2021

Despite decades of effort and staggering financial support, the cardioprotection field failed to deliver a drug that effectively reduces infarct size in patients. To address the limitations to such preclinical studies and promote progress in this critical area of medical research, we established the Consortium for preclinicAl assESsment of cARdioprotective therapies (CAESAR). The first step for CAESAR’s validation involved testing the “gold standard” for infarct size limitation: ischemic preconditioning (IPC). CAESAR tested the capacity for IPC to reduce infarct size in three species (at two sites/species): mouse (n=22‐25/group), rabbit (n=11‐12/group), and pig (n=13/group). During this validation phase, we confirmed that IPC significantly (p<0.05) reduced infarct size in all species, and, successfully established a multi‐center structure to support CAESAR’s operations, including: two distinct surgical centers for each species, a pathology core (to assess infarct size), a biomarker core (to assess cardiac protein release into blood), and a data coordinating center ‐ all with the oversight of a protocol review and monitoring committee of distinguished experts. Such an infrastructure promotes careful, blinded, randomized, statistically sound, and rigorous evaluation of cardioprotective agents. Thus, CAESAR is operational and represents a new approach to pre‐clinical cardioprotection studies.Grant Funding Source: Source of Support: National Institutes of Health (NIH)‐Heart Lung and Blood Institute (NHLBI) CAESAR Consortium‐U24 HL094373