bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel Anorexia Nervosa Refeeding Strategies: From Human to Rat and Back Again
Authors: Higgins Janine , MacLaean Paul , Giles Erin , Moore Rachel , Kasten Melanie , Pan Zhaoxing , Hagman Jennifer 
Published: June 2021

Aims1) To define changes in diet and physical activity (PA) that lead to inpatient treatment of anorexia nervosa (AN). 2) To use this data to refine a rat model of AN and examine the effects of a novel refeeding diet.Methods1) 15 females, 12–18 years, completed a FFQ, 24h diet recall, Pediatric PA Recall, and Modifiable Activity Questionnaire to assess changes in diet and the PA that lead to inpatient admission. 2) AN was induced in rats via free access to a running wheel and 1h access to low fat (LF) diet per day. Rats were re‐fed either LF (15% fat, 15% protein; AN LF) or test (30% fat, 28% protein, 1% leucine; AN moderate fat, AN MF) diet. Controls (C) were identical to AN LF but with no access to a running wheel (no AN). Body fat (BF) was assessed by QMR and fat pad weights. Energy balance was measured via indirect calorimetry.Results1) PA increased 300% prior to inpatient admission without any change in energy or macronutrient intake. 2) AN LF recovered 100% of initial weight after 7d of refeeding (8% BF) whereas AN MF did not return to 100% weight (4% BF) due to a 50% decrease in energy intake in AN MF vs AN LF with no difference in total energy expenditure. AN LF rats had fatty liver and higher visceral fat content than both C and AN MF.Conclusions1) Increased PA, not decreased energy intake, precipitated hospitalization for AN. 2) MF is not a dietary treatment for AN. However, LF diet causes fatty liver and visceral fat accumulation.
Erythropoietin induces myelin genes and the early growth factor 2 in oligodendrocytes through the classical erythropoietin receptor
Authors: Cervellini Ilaria , Annenkov Alexander , Chernajovsky Yuti , Ghezzi Pietro , Mengozzi Manuela 
Published: June 2021

Erythropoietin (EPO), a cytokine involved in erythropoiesis, is also neuroprotective in vitro and in vivo. EPO reduces disease severity in multiple sclerosis, an autoimmune‐inflammatory disease that causes demyelination. Immunomodulatory agents can delay the course of the disease, but nothing is available for remyelination.Despite EPO regulates erythropoiesis by the homodimeric EPO receptor (EPOR)2, variants of EPO not binding (EPOR)2 are still neuroprotective, so another receptor may be involved.This study investigated the role of EPO in myelination and the receptors involved. CG4 cells, a rat oligodedrocyte progenitor cell line able to differentiate to oligodendrocytes, were used. There was no effect of EPO on myelin gene modulation in CG4 wild type cells, lacking of EPOR. However, in CG4 cells modified to overexpress EPOR, EPO increased myelin genes in a receptor dependent manner. In addition, the early growth response gene EGR2, involved in peripheral myelination, was expressed in these cells and increased by EPO treatment.The correlation between EGR2 and myelin genes in oligodendrocytes, under investigation, could be a new finding in the study of central myelination. Greater understanding of the effect of EPO on myelination and the mechanism involved will help looking for therapies promoting remyelination.Supported by BSMS and the European Regional Development Fund, TC2N
Anti‐amnesic effect of bioflavonoid and amino acid from Cnestis ferruginea in Mice
Authors: ishola ismaila O , Tota Santoshkumar , Adeyemi olufunmilayo O , Agbaje Esther O , Narender Tadigullopula , Shukla Rakesh 
Published: June 2021

IntroductionBrain aging is characterized by cognitive decline and memory deficits that could be the result of oxidative stress and impaired cholinergic function. Cnestis ferruginea (Connaraceae) is a shrub widely used in traditional African Medicine for the treatment of various painful and inflammatory conditions.ObjectiveThis study was carried out to investigate the effect of methanolic root extract of Cnestis ferruginea (CF) and its active constituents on scopolamine (3mg/kg, IP) induced memory impairment in mice.MethodsMemory function was evaluated by Morris water maze and passive avoidance tests. Biochemical parameters of oxidative stress and cholinergic function were estimated in brain after the completion of behavioural studies.ResultAdministration of CF (25–200mg/kg, PO) for three days inhibited acetylcholinesterase (AChE) activity in the brain and prevented scopolamine induced memory impairment in mice (p<0.05). Further, through activity guided assay CF‐2 and CF‐5 were isolated from CF. CF‐2 and CF‐5 (12.5 and 25 mg/kg, PO), administered for 3 days, ameliorated memory impairment induced by scopolamine in Morris water maze and passive avoidance tests (p<0.001). Further, CF‐2 and CF‐5 produced significant (p<0.05) inhibition of AChE activity in mice brain far better than tacrine (5 mg/kg, PO). The crude extract and its active constituents exhibited antioxidant effect as shown by significant (p<0.05) decrease in MDA level and elevated GSH level in mice brain.ConclusionThis study shows that CF‐2 and CF‐5 could be a novel drug in the management of dementia due to their potent antioxidant and AChE activity.
Ebp50: A Novel Biomarker for Resistance to Endocrine and HER‐2 Targeted Therapies in Breast Cancer
Authors: gu Guowei , Covington Kyle Richard , Fernandez Natalie Michelle , Andoˈ Sebastiano , Fuqua Suzanne A.W. 
Published: June 2021

BackgroudEBP50 functions as a molecular scaffold to coordinate ion transport and second messenger signal transduciton. Recently, a number of studies suggest a role for EBP50 expression in cancer progression.MethodsMicroarray profiling. Stable transfection. Soft agar and MTT growth assays. Immunoblot and immunoprecipitation assays. Confocal microscopy.ResultsThe mean levels of EBP50 were reduced in the tamoxifen (Tam) ‐resistant, metastatic breast tumors compared to Tam‐sensitive tumors. Knockdown of EBP50 decreased Tam sensitivity in MCF‐7 and ZR75B cells. EBP50 knockdown cells showed higher levels of phosphorylated HER2 and EGFR, as well as their downstream signalling pathways. PI3K/AKT inhibitors were able to restore Tam sensitivity in knockdown cells. Similarly, knockdown EBP50 in ERα/HER2 positive BT‐474 cells increased costitutive pHER2 and these cells were resistant not only to Tam, but also to Trastuzumab (Tras) treatment. EGFR inhibitor or Lapatinib were able to restore Tras sensitivity. We demonstrate that EBP50 is capable of binding to HER2 using immunoprecipitation and confocal microscopes, suggesting that EBP50 interacts directly with HER2. Our data suggest that EBP50 is a novel negative regulator of HER2 signaling, and its loss conferred resistance to both Tam and Tras. We hypothesize that EBP50 levels might be a new predictive biomarker for targeted therapy.
Treatment with Cromolyn Sodium at early reperfusion but not before ischemia attenuates intestinal ischemia/reperfusion induced lung injury in mice
Authors: Gan Xiaoliang , Luo Chenfang , Luo Gangjian , Li Shangrong , Hei Ziqing , Xia Zhengyuan 
Published: June 2021

Mast cell degranulation plays a key role in small intestinal ischemia/reperfusion (IIR)‐induced lung injury. Studies showed that administration of mast cell stabilizers both before ischemia and at reperfusion can dramatically attenuate IIR injury. However, the relative effectiveness of mast cell inhibition before ischemia or during reperfusion on IIR‐induced lung injury has yet to be determined. Cromolyn Sodium (mast cell stabilizer, 25mg/kg i.v.) was administrated either for 15 min before inducing small intestinal ischemia in mice by occluding the superior mesenteric artery for 30 min, or for 15 min upon reperfusion. Small IIR resulted in significant intestinal injury manifested as increased Chiuˈs scores with concomitant lung injury evidenced as elevations in lung injury scores, lung wet/dry weight ratio and increases in lung tissue tryptase and mast cell protease 7 protein expressions in lung in 3 hours after reperfusion, accompanied with decreased survival rates at 3 day after reperfusion (all P<0.05, vs. Sham control). All these changes were significantly alleviated in mice treated with Cromolyn Sodium on reperfusion (P<0.05, vs. IIR untreated) but not in mice pre‐treated with Cromolyn Sodium. The results indicate mast cell inhibition at early reperfusion is an effective therapeutic approach in attenuating intestinal IR mediated remote organ injury.Supported by NSFC grant (30901408)
Neuritogenesis initiated via the GPCR PAC1 requires cAMP and ERK signaling organized in a single linear pathway independent of PKA or Epac
Authors: Eiden Lee E. , Emery Andrew C. 
Published: June 2021

Both cAMP and ERK are necessary for neuroendocrine cell neuritogenesis initiated through the PAC1 receptor, a family B GPCR activated by the neuropeptide PACAP (Ravni et al., Mol Pharmacology, 73:1688–16708). However, it is not yet known whether cAMP and ERK are arranged in two parallel pathways employing known signaling mechanisms, or a novel, linear pathway. We have measured cAMP elevation, ERK phosphorylation, CREB phosphorylation, neuritogenesis and cAMP/PKA‐dependent promoter‐reporter gene activation after treatment with forskolin, cAMP analogs, and PACAP in Neuroscreen‐1 (NS‐1) cells, a PC12 variant enabling simultaneous morphological, molecular biological, and biochemical analysis. Forskolin (25 μM) and cAMP analogs (8‐Br‐cAMP, db‐cAMP, 8‐ CPT‐cAMP) stimulated ERK phosphorylation and neuritogenesis in NS‐1 cells. Both ERK phosphorylation and neuritogenesis were MEK‐dependent (blocked by 10 μM U0126) and PKA‐independent (insensitive to 30 μM H‐89 or 100 nM PKI). CREB phosphorylation induced by PACAP was blocked by H‐89. The Epac‐selective 8‐pCPT‐2′‐O‐Me‐cAMP (100–500 μM) activated Rap1 without affecting the other cAMP‐dependent processes. Thus, PACAP‐38 potently stimulated two distinct and independent cAMP pathways leading to CREB or ERK activation in NS‐1 cells. We have thus identified a PKA‐ and Epac‐independent signaling pathway leading from cAMP elevation to ERK activation and thence neuritogenesis, that involves a novel cAMP sensor whose effects are insulated from those mediated by cAMP through PKA and Epac.Supported by NIMH‐IRP project ZO1‐MH002386.
Intratracheal instillation of TiO2 increases carotid‐femoral pulse wave velocity by suppression of eNOS and increasing IL‐6 in artery in rat
Authors: Wang Jiun-Jr , Wang Chin-Hao 
Published: June 2021

BackgroundIn addition to the damages to the lungs, inhaled nanoparticles may induce systemic proinflammatory and prothrombotic effects; however, its impacts to the alternation of arterial wall property have not been investigated.MethodsStudies were performed on 32 male Sprague‐Dawley rats in 4 groups, in terms of different interventions [intratracheal instillation of titian dioxide (TiO2; D=20 nm; 4 mg/kg) or vehicle] and treatments [N‐acetylcysteine (NAC; 20 mg/kg; i.v.) or Xigris (10 mg/kg; i.v.); 5 min prior to TiO2 instillation]. The LV function and the carotid‐femoral pulse wave velocity (CFPWV) were assessed by the LV pressure‐volume and two intravascular pressure transducers, respectively. Blood were samples at baseline, 1, 3 and 5 hrs after TiO2 to assess serum creatine phosphokinase (CPK) and creatine kinase‐MB (CK‐MB). Nitric oxide (NO), methylguanidiene (MG), malondialdehyde (MDA) and C‐reactive protein (CRP) were examined at 5 hrs. The expressions of IL‐6 and eNOS in the thoracic aorta were examined.ResultsTiO2 instillation induced severe systemic thrombotic effects, increasing CFPWV by 50% (8.8±3.6 m/s vs. 13.7±4.0 m/s). Xigris pretreatment attenuated thrombotic effects with minor changes in biomarkers and CFPWV (12.9±4.1 m/s). NAC pretreatment attenuated the increase in CFPWV (10.1±2.6 m/s; P<0.05) along with reduced serum MG, MDA and CRP and tissue IL‐6 and increased eNOS, while thrombotic effects persisted.ConclusionIntratracheal instillation of TiO2 induced transit increase in arterial stiffness is associated with systemic inflammatory responses.
Inhibition of Rho‐kinase decreases fetoplacental perfusion pressure under both normoxic and hypoxic conditions
Authors: Vajnerova Olga , Kafka Petr , Herget Jan , Hampl Vaclav 
Published: June 2021

Acute hypoxia causes hypoxic fetoplacental vasoconstriction (HFPV). Rho‐kinase inhibits myosin phosphatase activity and therby modulates intracellular Ca2+ sensitivity of vascular smooth muscle and augments vasoconstriction. We tested whether inhibition of Rho‐kinase pathway in fetoplacental vessels inhibits HFPV. Isolated rat placenta was dually perfused (from both the maternal and fetal side) with physiologic salt solution saturated with normoxic gas mixture in constant flow rate. Rho‐kinase pathway was inhibited by Fasudil (10 μM) which caused significant decrease of fetoplacental perfusion pressure (from 38 ± 3 mmHg to 31 ± 3 mmHg, P < 0,01). Vasoconstriction induced by the acute hypoxic challenge was blocked. We measured fetoplacental perfusion pressure and fetoplacental vascular resistance as a relationship of vascular perfusion pressure to continually rising flow rate (P/Q). In acute hypoxia the slope of the P/Q relation was higher in the control group than in the group with Fasudil. The pressure axis intercepts with P/Q line did not differ. In summary, Rho‐kinase inhibition causes complete abolition of HFPV.Supported by GACR 305/08/0108 and 2nd Faculty of Medicine, Charles University
X‐ray fluorescence microscopy of cortical brain structures across scales
Authors: Lam Ann , Ohayon Elan Liss 
Published: June 2021

Although it is well recognized that endogenous metals play an important role in healthy brain function, relatively little is known about their precise colocalization with respect to their neurochemical counterparts and anatomical localization across scales. We used synchrotron‐based x‐ray fluorescence microscopy to explore this issue by imaging postmortem tissue from human cortical brain structures at multiple resolutions. Cortical tissue sampled from prefrontal, temporal and occipital postmortem brain structures were imaged at two beamlines at the Stanford Synchrotron Radiation Lightsource. Quantitative distributions of several metals were collected at resolutions ranging from 0.5 to 100 microns. Elemental maps of unstained tissue showed the differential distribution of metals such as zinc, iron, copper and calcium in gross brain structures as well as at the sub‐cellular level. The distribution of particular elements also varied across cortical tissue depth. We also illustrate the differential effects of various histological stains applied prior to x‐ray fluorescence imaging. The findings demonstrate the sensitivity of x‐ray fluorescence imaging and potential to be cross‐correlated with other neurochemical markers at scales ranging from the sub‐cellular to whole brain.Support: NIH
Effects of spaceflight on vasoconstrictor and mechanical properties of mouse cerebral arteries
Authors: Hanna Mina , Stabley John N , McCullough Danielle J , Dominguez James M , Muller-Delp Judy M , Behnke Bradley J , Taylor Curtis R , Delp Michael D 
Published: June 2021

There is evidence to indicate that cerebral blood flow is diminished in astronauts upon return to Earth. Further, data from ground‐based animal models simulating the effects of microgravity have shown enhanced vasoconstriction and stiffness of cerebral arteries. The purpose of this study was to determine the effects of 13 d spaceflight (STS‐135 shuttle mission) on myogenic vasoconstrictor and mechanical properties of mouse cerebral arteries. Basilar and posterior communicating arteries (PCoA) were harvested and prepared for in vitro experimentation. Myogenic vasoconstrictor responses were lower and vascular distensibility was greater in the basilar arteries of spaceflown mice (n=7) relative to ground control animals (n=12). The elastic properties of the PCoA, as characterized via nanoindentation, demonstrated a 37% reduction in stiffness from spaceflown mice relative to controls. These results demonstrate that spaceflight alters vasoconstrictor and mechanical properties of cerebral arteries and these changes may provide critical insight into the underlying cause of vision impairment in astronauts.Supported by NASA grant NNX09AP06G
Analysis of the osteogenic effects of TGF‐beta in a calvarial defect model
Authors: SOTO JUAN MANUEL SOLIS , MORENO VANESSA SOUSA , NAJERA ROSA ISELA SANCHEZ , CEPEDA MARIA ARGELIA AKEMI NAKAGOSHI , CEPEDA SERGIO EDUARDO NAKAGOSHI , MEESTER IRENE 
Published: June 2021

TGF‐beta is involved in several cellular processes, including acting as a growth factor.ObjectivesThe aim of this study was to investigate the effect of TGF‐beta on bone regeneration and osteocalcin production.MethodsCalvarial osteotomy defects were created in adult male Sprague‐Dawley rats, they received TGF‐beta in an absorbable collagen sponge. After 6 weeks, morphometric analysis of histological sections was performed to evaluate the osteoid and bone growth, and the immunoreactive cells to osteocalcin.ResultsTGF‐beta induced a significative increase (p<0.01) of osteoid and bone growth in comparison to controls. Similarly, tissues treated with TGF‐beta displayed a higher number (p<0.01) of immunoreactive cells to osteocalcin.ConclusionThe osteoinductive capacity of TGF‐beta is demonstrated, in terms of the production of osteocalcin (mineralization factor) and bone growth. This work was supported by PAICYT UANL.
Evidence that Leptin Signaling in POMC Neurons Regulates HDL‐c
Authors: Marino Joseph S , Dowling Abigail , Faulkner Latrice , Hill Jennifer W 
Published: June 2021

Mice lacking leptin or its receptor have elevated serum HDL‐c due to dysfunctional hepatic ApoA‐1 and ApoA‐2 regulation. Data from our lab suggests the brain's pro‐opiomelanocortin (POMC) neurons, a major target of leptin, are involved in mediating the affects of leptin on HDL‐c.Using cre‐Lox genetic recombination, we bred mice that lack leptin receptors (LepR) specifically on POMC neurons (LepRPOMC). We measured serum HDL‐c, LDL/vLDL, total cholesterol, triglycerides, and ApoA‐1 from LepRPOMC and littermate controls (LepRflox/flox).Serum HDL‐c and ApoA‐1 levels were significantly elevated in LepRPOMC compared to control mice. LepRPOMC mice also have elevated triglycerides, LDL/vLDL ratio, and exhibit obesity. Thus, the elevated HDL‐c and ApoA‐1 levels do not appear to act in a cardio‐protective manner. Instead, their elevation may be due to dysfunctional hepatic regulation of HDL‐c associated lipoproteins as demonstrated in mice lacking leptin or its receptor.We believe this is the first evidence for the contribution of specific leptin responsive neurons to the regulation of HDL‐c. Studies are ongoing to examine the mechanisms for leptin‐mediated regulation of HDL‐c.
MicroRNA‐16 regulates ENaC expression in alveolar epithelial cells
Authors: parthasarathy Prasanna Tamarapu , Yunus Asfiya , Ramanathan Gurukumar Kollongod , Huynh Bao , Fukumoto Jutaro , Lockey Richard F , Kolliputi Narasaiah 
Published: June 2021

ObjectiveMicroRNAs (miRNAs) have emerged as a novel class of gene regulators which play a critical role in complex diseases like acute lung injury (ALI). Our miRNA profiling studies in animal models of ALI revealed that miR‐146a, mir‐16 and miR‐155 were dysregulated. Mir16 targets Serotonin transporter (SERT) which is involved in serotonin uptake. Elevated levels of serotonin in ALI are known to regulate epithelial sodium channel (ENac) expression. The aim of this study is to investigate the functional effects of mir16 on SERT and ENaC in human alveolar epithelial cells (A549) in vitro.MethodsA549 cells were commercially obtained and cultured according to the manufacturer instructions. Cells were transfected with plasmid containing miR16 expressing or control vector by Lipofectamine. q PCR and immunoblot analysis were performed to assess the effects of miR‐16 on SERT, ENaC and other downstream signalling molecules.ResultsA549 cells transfected with miR16 decreased the expression levels of SERT when compared to controls. Dose dependant regulation of SERT was observed in untransfected A549 cells treated with serotonin. Increased expression of ENaC β was observed in miR16 transfected cells compared to controls.ConclusionmiR16 over expression altered SERT and ENaC expression in human alveolar epithelial cells.Research supported by:RO1HL105932(NIH) and 09SDG2260957(AHA)
Off Target therapeutic effects of commonly used drugs to treat acute mountain sickness
Authors: Lisk Christina , Irwin David , Connor Ian 
Published: June 2021

IntroductionAcute mountain sickness is a syndrome that effects ~60% of individuals ascending to high altitude, yet the etiology is still unclear. It has been proposed that reactive oxygen species (ROS) formed from acute high altitude exposure contribute to brain vascular leak and development of AMS. NF‐E2‐related factor 2 (Nrf2) is a transcription factor that regulates expression of greater than 90% of antioxidant genes.HypothesisWe postulated that some drugs currently used to treat AMS symptoms could induce Nrf2 activation and that by increasing anti‐oxidant status would decrease vascular damage from oxidative stress in hypoxic conditions.MethodsA MCF7 cell line stably transfected with a luciferase gene driven by an antioxidant response element, the known Nrf2 promoter, was used to screen. Drugs that showed favorable Nrf2 activation were further tested in brain microvascular endothelial cells to determine if they attenuated hypoxia induced ROS production and permeability. Finally, compounds were tested for their ability to induce Nrf2 and decrease brain leak (measured by Evans blue dye) in male Spraque Dawly rats exposed to high altitude (48 h, 19,000 ft).ResultsOf 9 drugs tested, Nifedipine and Methazolamide showed strong NRF2 activation. Cells in hypoxic conditions increased hydrogen peroxide production by two fold from normoxic. Pre‐treatment with Methazolamide, Nifedipine, and Protandim decreased ROS production back to normoxic concentrations. This response was blocked by siRNA against Nrf2. Resistance was decreased after 24 hr hypoxic exposure, which was restored to normoxic values with pre‐treatments of Protandim, Methazolamide, and Nifedipine. Only drugs that showed Nrf2 activation in‐vitro, decreased brain vascular leak, in‐vivo.ConclusionNrf2 activators are effective at reducing brain vascular leak from acute high altitude exposures.
The role of myostatin on skeletal muscle energy metabolism during rest and exercise
Authors: Reisz-Porszasz Suzanne , Abraham Andrea , Kovanecz Istvan , Lew Henry , Constantinescu Silvana , Porszasz Janos 
Published: June 2021

Myostatin (Mst) regulates skeletal muscle mass and adipogenesis, but its role in regulating metabolism and physical performance is unknown. We investigated three mouse models: Mst overexpressing transgenic [TG]; Mst knock‐out [KO]; wild type [WT]. Male (1 yr) mice were fed a regular (R), low carb (LC), high carb (HC) or high fat (HF) diet for 6 wks. Maximal (MS) and critical (CS) running speed and ‘work capacity’ (W’) were determined using a treadmill at 5% incline. Results were allometrically scaled for body mass. Calorific intake was not different among diets. Compared to R, body mass was lower all animals in LC (5–8%; P<0.05), but in HC was 9% lower only in KO (P<0.05). During HF body mass was 41% greater in TG than WT (P<0.05). MS was faster among TG animals, especially in LC diet (TG=50±2; WT=40±1; KO=35±1 m/min; P<0.05), and was slower in KO. Also, CS was slower in TG than WT (P<0.05), but only during HC and HF diets. W’ was independent of diet but significantly greater in TG (TG=41±10 m; WT=25±5 m; KO=18±5; P=0.012). The results are consistent with a metabolic regulatory role of Mst, where overexpression results in a greater reliance on â‐oxidation and a reduced glycogenolytic rate.Supported by U54RR022776, SC1GM089648‐01A1.