bluuebunny/crossref_metadata_2025_split huggingface dataset:
Decreased nitric oxide (NO) Availability Contributes to the Impaired Mitochondrial Biogenesis and Oxidative Stress in Fetal Lambs with Pulmonary Hypertension (PPHN)
Authors: Afolayan Adeleye 
Published: June 2021

We previously showed increased oxidative stress and ATP depletion in PPHN. We hypothesize that decreased NO levels and increased mitochondrial oxidative stress impairs mitochondrial function in PPHN.Methods‐ PAECs were isolated from control fetal lambs and lambs with PPHN induced by prenatal constriction of the ductus arteriosus. We knockdown eNOS in control PAEC using siRNA, and treated PPHN PAEC and eNOS depleted cells with 200µM detaNONOate (deta), an NO donor, for 18h. We quantified mtDNA copy number, electron transport chain subunits complexes I‐V (CI‐V) and ATP levels at baseline and following deta treatment using rT‐PCR, WB and bioluminescence assay. Levels of PGC1α, Sirti1, and p‐AMPKα were also assessed by WB. Effects of NO on basal O2 consumption rate (OCR) and mitochondrial superoxide (mtO2̅) in PPHN were assessed using dihydroethidium and seahorse XF24 assay. We also assess changes in SOD2 expression and specific activity following deta treatment in PPHN PAEC using WB, Cayman activity assay and immunoprecipitation.Results‐MtDNA copy number is decreased in PPHN. Levels of PGC1α, Sirti1 and p‐AMPKα were also decreased. This is accompanied by decreased CI‐V and ATP levels. eNOS knockdown decreased CI‐V levels in control PAEC. Deta increased mtDNA copy number, CI‐V and ATP levels in PPHN and in eNOS depleted cells. Basal OCR is decreased albeit, ATP‐linked O2 consumption is increased in deta treated PPHN‐PAEC. Increased bioenergetics is accompanied lower mtO2‐ levels and increased SOD2 expression and activity.Conclussion‐Alteration in mitochondrial metabolism is a key feature of PPHN, and has important therapeutic implications. In PPHN, NO restores mitochondrial biogenesis and decreases mtO2̅ levels.
In vivo MEMRI Reveals Decreased Activation of the Hippocampal and Amygdaloid Regions in a Rodent Model of RAS‐Dependent Hypertension
Authors: Zubcevic Jasenka , Perez Pablo , Ahmari Niousha , Marulanda Carvajal Jessica , Raizada Mohan , Febo Marcelo 
Published: June 2021

Brain RAS affects pathogenesis of neuronal disease by contributing to neuroinflammation in animal models including hypertension. Thus, we hypothesized that the overactive brain RAS will directly contribute to decreased neuronal activity in cognitive brain areas. METHODS: Manganese‐enhanced magnetic resonance imaging (MEMRI) yielded in vivo mapping of spontaneous neuronal activity in the amygdala and hippocampus in a rodent model of overactive brain RAS and neuroinflammation, the spontaneously hypertensive rat (SHR) compared to the Wistar Kyoto (WKY). Rats were treated with manganese chloride (MnCl2 30 mM, i.p.; 16‐20 hrs) and T1‐weighted images were obtained (4.7T). Coronal slice scans were automatically segmented (FMRIB FSL and Ekam Solutions) and analyzed for differences in normalized signal intensity. RESULTS: We observed lower signal intensity in basal/central amygdala (53%), lateral (73%) and medial amygdala (50%), CA2 (46%) and CA3 hippocampal nuclei (30%), central gray (49%), and habenula (15%), in the SHR vs WKY rats.CONCLUSIONTo our knowledge, this is the first MEMRI assessment of neuronal activity suggesting abnormal hippocampal and amygdaloid neurocognitive functioning in the SHR. This supports the role of hypertension in cognitive decline and advocates for a therapeutic approach for neuronal disease by regulating the brain RAS.NIH HL33610.
Paraventricular Nucleus in Acupuncture's Inhibition of the Von Bezold Jarsich Reflex
Authors: Tjen‐A‐Looi Stephanie , Guo Zhi‐Ling , Nguyen Ai‐Thuan , Longhurst John 
Published: June 2021

Electroacupuncture (EA) stimulates specific somatic sensory nerves underlying P5‐6 acupoints and modulates parasympathoexcitatory reflex responses through actions in the brainstem. Although Bezold Jarisch‐induced decreases in blood pressure and heart rate reflex responses are modulated by acupuncture through actions in nucleus tractus solitarius and nucleus ambiguus, the role of the hypothalamus is unclear. The paraventricular nucleus (PVN) regulates sympathetic outflow and blood pressure. Vagal afferent stimulation activates neurons in the PVN but little is known about cardiopulmonary physiological actions in this nucleus. We therefore hypothesized that the PVN participates in the Bezold Jarisch responses and EA modulation of parasympathoexcitatory cardiovascular responses. Rats were anesthetized, ventilated, and heart rate and mean blood pressures were monitored. Application of phenylbiguanide (PBG) every 10 min close to the right atrium induced consistent depressor and bradycardia reflex responses. Unilateral microinjection of kainic acid or kynurenic acid in the PVN reduced the reflex responses. Thirty min of bilateral EA at P5‐6 acupoints reduced the depressor and bradycardia responses lasted for >60 min. Unilateral inhibition of the PVN with 50 nl of naloxone reversed the EA‐inhibition during repeated PBG‐induced responses. EA‐related c‐Fos PVN neurons were juxtaposed to endorphinergic PVN fibers. Thus, cardiopulmonary PVN responses are important in processing acupuncture modulation of cardiovascular inhibitory reflexes.Funded by HL‐63313, HL‐72125.
How Does the Brain Talk to the Arteries and Heart?
Authors: Blaustein Mordecai , Chen Ling , Song Hong , Leenen Frans , Hamlyn John 
Published: June 2021

In many hypertension (Htn) models, myogenic tone (MT) in isolated small arteries is increased. MT is regulated mainly by Ca2+ transporters. Arterial transporter expression is “reprogrammed” in many Htn models: e.g., Na/Ca exchanger (NCX) and SR Ca2+ pumps (SERCA2) are increased; this enhances constriction and MT. In heart failure (HF), cardiac Ca2+ transporter “reprogramming” impairs contraction: e.g., NCX1 is increased, and SERCA2 expression or function is reduced. Do these cardiovascular (CV) changes in Htn and HF have a common trigger? The brain RAAS is activated in both Htn and HF. Central Ang II infusion increases BP, circulating endogenous ouabain (EO), and arterial NCX and SERCA2 expression; brain RAAS blockade prevents all effects (Hamlyn et al., PloS one 9: e108916, 2014). Here we induced Htn in rats (mean BP = 124 vs Control = 99 mm Hg) and mice (139 vs C = 110 mm Hg) with sc low dose Ang II (150‐350 ng/kg/min) and a high (2‐6%) salt diet. Also, in mice, coronary artery ligation caused ~45% LV myocardial infarction (MI) and HF: a 38±4% fall in LV ejection fraction at 8 wks post‐MI. In both Htn and HF, plasma EO increased (1.31‐2.59 nM vs C = 0.07‐0.53 nM) as did expression of arterial NCX (1.7‐1.8xC) and SERCA2 (2.0‐2.3xC) and cardiac NCX (1.7‐1.9xC), but cardiac SERCA2 expression declined (0.58‐0.74xC). In vitro 48‐72 hr treatment with 50‐100 nM ouabain, but not digoxin, increased NCX and SERCA2 protein in primary cultured arterial myocytes (published), and NCX (1.3‐1.7xC) in cardiomyocytes.Conclusionplasma EO is the signal from the brain that triggers Ca2+ transporter reprogramming in both Htn and HF. The novel slow brain RAAS‐plasma EO‐CV system modifies responses to the rapid RAAS‐activated sympathetic nerve pathway, and both modulate CV function in Htn and HF.
ROLE OF BARORECEPTORS IN HYPOTENSION AND RENAL SYMPHATHOINHIBITION INDUCED BY BLOCKADE OF THE MEDIAN PREOPTIC NUCLEUS
Authors: MOURÃO Aline , DA SILVA ELAINE , DOS SANTOS MOREIRA MARINA , PEDRINO GUSTAVO 
Published: June 2021

The present study sought to evaluated the autonomic and cardiovascular effects of the MnPO inhibition following the sinoaortic denervation. Male Wistar (WT) rats and spontaneously hypertensive rats (SHR; 250‐300g) were anesthetized (ketamine 100mg.kg‐1, b.wt.; and xylazin 20mg.kg‐1, b.wt.), and submitted to sinoaortic denervation. Femoral artery and vein were catheterized and led subcutaneously to exit between the scapulae. In the following day, animals were anesthetized with urethane (1.2g.kg‐1, b.wt.) and instrumented for recording renal sympathetic nerve activity (RSNA) and for nanoinjections of saline (NaCl; 150 mM) and muscimol (GABAA agonist; 4 mM) into the MnPO. In WT group, the inhibition of the MnPO with muscimol reduced MAP in both sham (n=5) and denervated (17.5±0.8 vs. ‐28.0±6.5 mmHg, respectively; 3min; n=5). This response was maintained throughout the experimental period (‐15.9±2.3 vs. ‐22.5±4.3 mmHg; 30min). The sympathoinhibition induced by inhibition of MnPO were similar between sham (‐23.2±1.8%; 3min) and denervated WT rats (‐22.0±5.2%; 3min). In SHR groups, the blockade of the MnPO also promoted decrease in MAP, however this response was greater in denervated SHR (‐44.7 ± 7.1 mmHg; n=4) compared to the sham (‐21.0 ± 5.6 mmHg; n=5). We also observed similar decrease of RSNA induced by MnPO inhibition in SHR (‐34.9±8.2%; 3min) and denervated SHR (37.5±8.6%; 30min). The results demonstrated that aortic and carotids afferents participate in the modulation of autonomic and cardiovascular responses induced by the blockade of the MnPO.SupportCNPq and FAPEG.
A Cross Sectional Study of Modifiable Cardiac Risk Factors in Young Adults of Different Personality Traits
Authors: Nepal Ojashwi , Bhattarai Supriya , Khanal Kishor , KC Rojan 
Published: June 2021

Even the young adults who are residing in the urban and suburban areas are unaware of many factors associated with increasing health risks. These factors are obesity, hypertension, physical inactivity, smoking habit and poor nutritional status. Those are directly associated with cardiovascular disease which is the leading cause of disability and premature death.The study was to predict cardiac risk among young adults through modifiable cardiac risk factors of different personality traits.A cross sectional study was conducted among 153 subjects at Kavre District, Nepal. The study of personality traits was based on the BFI questionnaire. The volunteers in this study were of 18 to 24 years in age. Each subject was asked to fill a set of standard questionnaires related to personality, physical activity and nutritional status after obtaining the consent from them. In addition, their Blood Pressure, Height and Weight were measured. Body Mass Index and Basal Metabolic Rate were calculated. The analysis was done using ANOVA and Independent T‐test.Our study demonstrated that, the majority of the subjects exhibited two key personality viz: Agreeableness (41.83%) and Openness (48.36%). The numbers of physically active individuals were also high under these personality traits

Personality Types
Exercisers
Non‐exercisers

Agreeableness (41.83%)
36.70%
47.30%

Extraversion (3.26%)
5.10%
1.40%

Openness (48.36%)
49.40%
47.30%

Neuroticism (1.30%)
0%
2.70%

Conscientiousness (5.22%)
8.90%
1.40%

The nutritional count reveals that 112 (73.2%) subjects have good nutritional status

Nutritional status
Exercisers (No. of subjects)
Non‐exercisers (No. of subjects)

Good
60
52

Moderate risk
15
12

High risk
4
10

Utilizing the independent t‐test, nutritional status and personality traits of exercisers and non‐exercisers were found significantly different.Exercisers and non‐exercisers have different personality traits and nutritional status. Greater percentage of young adults in the studied population do not fall under cardiac risks.Exercise, Neuroticism, Blood‐pressure, Obesity, Risk‐factors
Bone Density and Strength Decreased in a Mouse Model of Diabetes, db/db Mice
Authors: Samadfam Rana , Rocheford Erik , Cornicelli Joe , Smith Susan 
Published: June 2021

Diabetes is a disorder of glucose metabolism and uncontrolled or poorly controlled glycemia has the potential to impair all organs. Cardiovascular disease, renal impairment, neuropathy, inflammation, ocular changes and impaired wound healing are well recognized complications of this disease, sometimes even in the presence of reasonably well‐controlled blood glucose. Recently osteoporosis and increased fracture risk has also been added to this long list. To complicate matters, some therapies that provide good glycemic control have adverse effects on the skeletal system further compromising already fragile bones in diabetic patients.Db/db mice are commonly used model for diabetes research. The goal of this work was to investigate the skeletal integrity in this model. Bones were collected from db/db mice and their wild type littermates. Femurs were scanned using pQCT and BMC, BMD and also bone geometry parameters were obtained at the metaphysis and also diaphysis site. The bone strength was obtained by the three point bending test. The results indicate that the db/db mice had smaller bones with lower bone density. The bone strength of these animals was also compromised. These results highlight the importance of the consideration to include bone assessment in safety studies to monitor for diabetic complications
Alterations in Metabolic Relations and Adiposity during and after Cigarette Smoke Exposition, in Young Female and Male Mice
Authors: Gaspar‐Reis Rejane , S Silva Cynthia , Santos Aline , Rangel Ninive , Albuquerque Karine , Abreu‐Villaça Yael , Souza Erica , Nascimento‐Saba Celly Cristina 
Published: June 2021

Cigarette smoking is worrisome in adults and also in adolescents. This study aim evaluates the influence of smoking in puberty and the consequences of withdrawal, body composition of female and male mice.At 35d mice were exposed to 3R4F cigarette smoke, 8 h/day for 15d (S, n =24).Then, half of animals were evaluated and the other half was maintained and evaluated thirty days after stop exposure (30d AS). An unexposed group accompanied the events (NS, n = 24). Body mass, body composition, food intake, blood, ipGTT and adipose tissue were evaluated. During exposure food intake was similar all groups, however, S groups showed low body mass gain. 30dAS, S groups increased body mass and food intake in females. In regard blood, males didi not alter insulin or ip GTT during exposure whilst females had high insulin levels and glycemia at 30min. Withdrawal induced in males, high insulin and low glycemia the ipGTT and in females normal insulin and low glycemia.The set of results indicates different response cigarette smoke in young that seem to start in females and lead malefic metabolic alterations in adulthood.
MicroRNA‐150 Knockout (miR150‐KO) Prevents Age‐Related Glucose Intolerance and Extends Life‐Span
Authors: Wang Shieley , Liu Xiaocan , Sun Zhongjie 
Published: June 2021

Background and HypothesesAgeing is associated with metabolic syndrome. The purpose of this study is to assess if miR150 regulates glucose tolerance, insulin sensitivity, and lifespan in male mice.Methods and ResultsThirteen wild‐type (WT) and 32 Mir150‐KO male mice were used. Mir150‐KO decreased insulin sensitivity and improved aging‐related glucose intolerance. Mir150‐KO extended lifespan in male mice compared with the age‐matched WT mice. The longest lifespan was 37 months in Mir150‐KO mice and 30 months for WT controls (p<0.05 Kaplan Meier Analysis). The survival percentage was 28.1% in the Mir150‐KO group and 7.7% in the wild type group at the age of 30 months. IHC data showed that the pancreatic insulin content was increased by Mir150‐KO. Western blot analysis indicated that Mir150‐KO decreased insulin/IGF‐1 receptor and Akt activity in the kidneys but increased ACCs and p‐ACCs in the liver of aged mice.ConclusionMir150‐KO extended lifespan by suppressing the renal insulin/IGF‐1/Akt activity and upregulating the hepatic ACC activity.
Multiplex Analysis of Biomarkers in Thyroid Cancer
Authors: Anderson Shaya , Fuerstenberg Richard , Brumbaugh Kathy , Kalyuzhny Alex , Sommer Stacy 
Published: June 2021

Thyroid cancer is the most common endocrine cancer, the incidence of which has been rapidly increasing over the last few decades. Traditionally, thyroid tumors are classified into two major groups based on morphologic and clinical features: undifferentiated (anaplastic) carcinomaand differentiated carcinoma (papillary, follicular and medullary). Early identification and diagnosis is essential for effective treatment.Cytokines, chemokines and growth factors play a critical role in the growth and differentiation of many target cells. These bio‐active molecules regulate the development and growth of both normal and neoplastic thyroid tissues. In addition, many cytokines and chemokines have been shown to generate antitumor responses. In patients with thyroid cancer, these molecules are often dysregulated, making them potentially useful as diagnostic biomarkers.In this study, thyroid carcinoma tissues were collected from patients diagnosed with papillary, follicular or medullary carcinoma. Paraffin‐embedded tissue sections were analyzed by IHC and adjacent frozen tissues were homogenized and assayed for biomarkers as large multiplexes using R&D Systems™ Luminex® Screening Assays (Catalog# LxSAH). Initial testing was done using a multiplex of 27 relevant biomarkers. Results were verified by western blotting. The multiplex data was used to establish a biomarker profile for each of the three cancer types.In a follow up study, sera from five thyroid cancer patients and five apparently normal healthy individuals were evaluated using the same multiplexes. The serum results were compared to the tissue profiles with the intent of aiding in identification of the cancer type.
Thioesterase Superfamily Member 2 (Them2) Channels Fatty Acids to Glycerol‐3‐Phosphate Acyltransferase‐1 (GPAT1): Role in Hepatic Insulin Resistance
Authors: Minami Akihiro , Cooper Daniel , Coleman Rosalind , Cohen David 
Published: June 2021

Them2 is a mitochondria‐associated acyl‐CoA thioesterase, which promotes fatty acid oxidation within hepatocytes apparently by generating free fatty acids that are re‐esterified to CoA by long chain acyl‐CoA synthetase 1 (ACSL1) for uptake by carnitine palmitoyl transferase 1. ACSL1‐generated fatty acyl‐CoAs may also become substrates for GPAT1, which initiates the synthesis of glycerolipids. Diacylglycerols and phosphatidic acid suppress insulin signaling by activating PKCε or inactivating mTORC2, respectively, and GPAT1 overexpression in liver promotes hepatic insulin resistance. Because livers of Them2‐/‐ mice exhibit increased sensitivity to insulin, we examined whether Them2 promotes GPAT1‐mediated suppression of insulin signaling. Using recombinant adenovirus, GPAT1 or GFP was overexpressed in mouse livers. GPAT1 but not GFP overexpression promoted hepatic synthesis of glycerolipids in both Them2+/+ and Them2‐/‐ mice. As evidenced by increased ratios of membrane/cytosolic PKCε, GPAT1 overexpression activated PKCε in livers of Them2+/+ mice, an effect that was attenuated in the absence of Them2 expression. Consistent with the contribution of Them2 to GPAT1‐induced hepatic insulin resistance, when primary mouse hepatocytes were infected with GPAT1 adenovirus, insulin‐mediated Akt phosphorylation was increased at S473 and T308 in the absence of Them2 expression. These findings implicate Them2 in channeling fatty acids to GPAT1 and in the pathogenesis of hepatic insulin resistance.Support: NIH DK48873, DK56626 and DK56598; Sumitomo Life Welfare and Culture Foundation
Unbiased Glycomics in Cardio‐pulmonary Disease
Authors: Ishihara Mayumi , Zhang Hanrui , Kumagai Tadahiro , Stalnaker Stephanie , Bridger Robert , Wells Lance , Tiemeyer Michael , Reilly Muredach , Azadi Parastoo 
Published: June 2021

Cardiovascular diseases (CVD) are the most common causes of death in developed countries and their prevalence rate is rapidly growing. Understanding of changes in proteins, sphingolipids and their post‐translational modifications (PTMs) associated with disease progression are essential for elucidating the mechanisms by which these changes influence risk for CVD.Toward this end, MS analyses were performed in (a) platelets (resting, activated and sheddome preparations) of healthy humans, (b) in cultured human coronary artery endothelial cells and iPS‐derived endothelial cells and (c) in a pilot case‐control study of early onset MI cases vs. chronic coronary atherosclerosis cases vs. older disease free controls drawn from our large PennCath cohort angiographically defined patients with heart disease.For platelet study, collected resting platelets were activated in vitro. The activated‐platelet supernatant was analyzed as sheddome. Our MS analysis indicated that N‐glycans from resting and activated platelets are a mixture of high‐mannose type and complex type structures. Comparatively, those from sheddome were primarily sialylated complex type structures. The main O‐glycans in resting platelets and sheddome were O‐glucose type structures. For glycosphingolipids, expression levels of lactosylceramide and ganglioside GM3, were decreased and increased, respectively, following platelet activation. Moreover, a main glycoprotein and its PTMs in sheddome were identified by lectin blotting and proteomic/glycoproteomic analyses. Overall, our findings provided the basis for the further studies understanding the mechanism of the occurrence of CVD.
Identifying Transcriptional Changes in a Conditional Knockout Mouse
Authors: Burgan Richard , Dries Daniel , Yu Gang 
Published: June 2021

gamma‐secretase is a multi‐subunit, proteolytic complex that is directly involved in the pathogenicity of Alzheimer's disease. Recently, a mouse was developed in which gamma‐secretase was conditionally knocked out of oligodendrocytes, or the myelinating cells of the brain. Knockout of gamma‐secretase produced a striking non‐cognitive neurological phenotype, reminiscent of schizophrenia. Here, we compare the transcriptomes of cKO mice and control mice by means of RNA‐seq analysis to identify candidate genes that may explain the complex neurological phenotype exhibited by our conditional knockout mice.Grant Funding Source: Supported by National Institute of Neurological Disorders and Stroke Grant 1R01NS079796
Combination of Anti‐Inflammatory Nutrients shows Synergistic Potential at Modulating Pro‐Inflammatory Cytokines in an In Vitro Setting
Authors: Connaughton RM , Kirwan AM , McMorrow AM , McGillicuddy FC , Lithander FE , Roche HM 
Published: June 2021

LC n‐3 PUFAs, vitamin C and EGCG display anti‐inflammatory properties. Studies looking at these nutrients individually have shown mixed results. A combination of anti‐inflammatory nutrients may be more beneficial at modulating inflammation. We hypothesize that the synergistic potential of a combination of anti‐inflammatory nutrients would be greater than the effect of single nutrients and polyphenols.J774.2 macrophages were pre‐treated with EPA, DHA, vitamins C and E, EGCG and lycopene (50µM) individually or in different combinations (final concentration 50µM) for 24hrs. J774.2 macrophages were LPS‐stimulated (10ng/ml) for 3‐24hrs to assess cytokine secretion. ATP (5mM) was added to assess IL‐1β. Several signalling pathways were determined by immunoblot analysis.All 6 compounds combined attenuated LPS‐induced IL‐6 and ATP‐induced IL‐1β secretion. The pathways being modulated by the nutrients varied. LC n‐3 PUFAs reduced LPS‐induced TNF‐α, IL‐6 and IL‐1β. The anti‐oxidant/polyphenols modulated IL‐6 and IL‐1β as effectively as LC n‐3 PUFA, but did not alter TNF‐α. The mechanistic basis of the IL‐1β response was different. Pro‐IL‐1β priming was significantly reduced by LC n‐3 PUFA, whereas the anti‐oxidant/polyphenols did not reduce pro‐IL‐1β, indicating they modulate activation of IL‐1β.The anti‐inflammatory potential of LC n‐3 PUFA versus anti‐oxidant/polyphenol combinations is very different. Additionally, LC n‐3 PUFA reduced priming of pro‐IL‐1β, whereas the anti‐oxidant/polyphenol combination did not.Funding: National Children's Research Centre, Ireland & SFI 11/PI/1117