bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stem‐Like Cells in Breastmilk for Hospitalized Preterm Infants
Authors: Briere Carrie‐Ellen , Jensen Todd , McGrath Jacqueline M , Finck Christine 
Published: November 2023

Breastmilk stem cells are a relatively new discovery in the scientific community. There are still many unknowns about their specific mechanisms of interaction; however, it has been hypothesized that their presence contributes to growth and development of the breastfed infant. Our research team is the first known team to enroll mothers of hospitalized preterm infants during the first few weeks of lactation and compare stem cell phenotypes and expression to mothers of healthy full‐term infants. The purpose of this study was to evaluate the feasibility of NICU breastmilk collection and the comparison of preterm and full‐term breastmilk cells. We enrolled mothers of preterm infants (n=7; range 26 4/7 – 34 5/7 weeks gestational age at birth) and mothers of healthy full‐term infants (n=4; range 39 5/7–40 5/7 weeks gestational age at birth). Flow cytometry and qRT‐PCR analysis were used to assess the prevalence of a variety of pluripotent and mesenchymal stem cell markers. Overall, cells with stem‐like characteristics were identified in both preterm and full‐term breastmilk samples. There was large variability among the amount of each stem cell phenotype present, as well as in the expression of specific markers. Preliminary results indicate that gene expression in the majority of the tested markers were significantly different between the preterm sample and the full‐term sample. In conclusion, there are individual differences in the cellular composition of breastmilk, and this variation results in differential expression of phenotypic markers and gene expression of breastmilk cells with multipotent and pluripotent characteristics. The science of breastmilk stem cells is new and there is future potential to use these easily accessible stem cells in regenerative medicine. Future studies will explore the relationship of breastmilk stem cell characteristics to neonatal health, most notably their regenerative and protective potential.Support or Funding InformationNational Association of Neonatal Nurses and Foundation for Neonatal Research and Education
Endothelial Mitochondria Regulate Local Calcium Signalling in Mesenteric Arteries From Mice
Authors: Toussaint Fanny , Béziau Delphine , Charbel Chimène , Blanchette Alexandre , Mayer Gaetan , Comtois Philippe , Ledoux Jonathan 
Published: November 2023

Local calcium (Ca2+) signals are crucial for endothelial functions, including regulation of underlying smooth muscle cell contractility. Ca2+ pulsar is an endothelial IP3R‐dependent Ca2+ signal restricted to myoendothelial projections (MEP). Targets for this spatially‐discrete Ca2+ signal such as KCa3.1 channels, NOS3 and CaMKII have been previously described. However, determinants for Ca2+ pulsar kinetics and stochasticity remains poorly understood. Mitochondria are an important regulator of intracellular Ca2+ dynamics in several cell types such as pancreatic acinar cells. It has thus been hypothesized that mitochondria are an important modulator of Ca2+ pulsar. Mitochondrial influence on Ca2+ pulsar was explored on cut‐opened mesenteric resistance arteries using a high‐speed confocal microscope. Inhibition of mitochondrial uniporter‐dependent Ca2+ uptake (Ru360) increased the surface covered by a Ca2+ pulsar (+30%). Conversely, stimulation of mitochondrial Ca2+ uptake (kaempferol) reduced Ca2+ pulsar's spreading (−20%), suggesting that mitochondria could limit Ca2+ pulsars propagation. Interestingly, inhibition of mitochondrial Ca2+ efflux (CsA for mPTP; CGP37157 for NCLX) had little if any effect on spatial dispersion of a Ca2+ pulsar. However, de novo Ca2+ pulsar sites were observed following exposure to CsA/CGP. Mitochondria might thus control subcellular Ca2+ levels within MEP to modulate IP3R activity. Electron microscopy showed clustering of mitochondrial distribution near the MEP. These results suggest that mitochondria might play a significant role in regulating local endothelial Ca2+ signalling and then, modulate vascular tone.Support or Funding InformationFRQS, CFI, SQHA and CIHR
Estradiol Deficiency Leads to High miR‐21 Level in Skeletal Muscle of Ovariectomized Mice
Authors: Karvinen Sira M , Laakkonen Eija , Le Gengyun , Collins Brittany C , Mader Tara L , Lowe Dawn A 
Published: November 2023

The loss of skeletal muscle strength is a consequence of aging. In women, there is an even greater loss of muscle strength due to reduced ovarian hormones that occurs during menopause. Estradiol (E2) has been shown to mitigate the detrimental effects on muscle strength in females. However, the underlying molecular mechanisms of estradiol's beneficial effects are not completely understood. Here we have focused on signaling by microRNAs (miRs) which are known to be potential biomarkers for disease (1). miRs are small RNA molecules that work as post‐transcriptional regulators by blocking translation. Previously we have shown in women that there are several E2 responsive miRs in skeletal muscle (2). MiR‐21 is a specific miRNA that is frequently up‐regulated in cancer and has a key role in apoptosis. Apoptosis signaling has a potential role in muscle atrophy contributing to loss of muscle strength with aging.METHODSAdult C57BL/6 mice were either sham operated (ovary‐intact) or ovariectomized (OVX) under isoflurane anesthesia. Four weeks later, extensor digitorum longus (EDL) muscles from the OVX mice were isolated and underwent a series of repetitive maximal isometric tetanic contractions in the presence or absence of E2 in the bathing medium, after which muscles were snap frozen and analyzed for miR‐21. Gastrocnemius muscles and blood serum were also collected for miR‐21 analysis.RESULTSOVX mice had 11‐fold higher miR‐21 levels in gastrocnemius muscles (p < 0.01) compared to sham mice, but serum levels did not differ (p = 0.18). Electrically stimulated muscle contractions in vitro increased the expression of miR‐21 in EDL muscles, whereas acute E2 exposure diminished the contraction‐induced upregulation of miR‐21 in OVX mice.CONCLUSIONOur preliminary results show that E2 deficiency via OVX leads to high miR‐21 levels in skeletal muscle and that a short term exposure of muscle to E2 can blunt muscle contraction‐induced upregulation of miR‐21. More studies are needed to find out mechanisms through which E2 affects miR‐21 levels.Support or Funding InformationThis study is supported by NIH grant R01‐AG031743.
ANNONA SENEGALENSIS SHOWS POTENT ANTI‐DIABETIC ACTIVITY BY ATTENUATING DNA FRAGMENTATION IN OXIDATIVE INJURY AND INHIBITING KEY‐ENZYMES LINKED TO TYPE 2 DIABETES
Authors: Erukainure Ochuko L. , Islam Shahidul 
Published: November 2023

The leaves and stem bark of Annona senegalensis were investigated for their anti‐oxidative vis‐à‐vis anti‐diabetic potentials in vitro. Extracts from sequential extraction with solvents of increasing polarity (n‐hexane, ethyl acetate, ethanol and aqueous) of the leaves and stem barks were subjected to in vitro antioxidant assays using the 2,2′‐diphenyl‐1‐picrylhydrazyl (DPPH) scavenging and Ferric reducing antioxidant power (FRAP) protocols respectively. Their inhibitory effects were investigated on intestinal α‐glucosidase, hepatic and pancreatic lipases, glucose‐6‐phospatase and pancreatic ATPase activities. Their antioxidant and anti‐apoptotic effects on Fe2+ ‐ induced oxidative injuries in pancreatic and hepatic tissues were also investigated ex vivo. The extracts showed potent free radical scavenging activity and significantly (p<0.05) inhibited all studied enzymes, with the stem bark extract showing better activity. Superoxide Dismutase (SOD) and Catalase activities were significantly (p<0.05) increased in both pancreatic and hepatic tissues with concomitant elevation of reduced glutathione (GSH) levels as well as reduced levels of malondialdehyde (MDA). The extracts significantly inhibited DNA fragmentation in both tissues. These activities were dose – dependent. These results indicate the anti‐oxidative, anti‐diabetic and anti‐obesogenic potentials of A. senegalensis, with the ethanolic extract of stem bark showing the best activity. Thus, giving credence to its antidiabetic folkloric claimsSupport or Funding InformationUniversity of KwaZulu‐Natal, Durban 4000, South Africa
Dietary and Lifestyle Determinants of Vitamin D Status in Filipino Women Living in Korea: FiLWHEL Study
Authors: Kim Soonji , Abris Grace , Provido Sherlyn Mae , Shin Wookyoung , Hong Sangmo , Yu Sung Hoon , Lee Chang Beom , Lee Jung Eun 
Published: November 2023

ObjectiveWe aimed to assess vitamin D status and to identify dietary and lifestyle determinants for vitamin D status among Filipino women living in Korea of the Filipino Women's Diet and Health Study (FiLWHEL).MethodsFilipino women who have been married to Korean men were recruited from March 2014 to April 2016. We included a total of 486 Filipino women aged 20–55 years old in our analysis. Serum levels of 25 hydroxyvitamin D (25(OH)D) were measured using electrochemiluuminescence immunoassay. We asked participants about demographic and lifestyle factors through face‐to‐face interview and assessed anthropometric measures using bioimpedance method. We identified dietary, demographic, anthropometric, and lifestyle factors associated with circulating 25(OH)D levels using the linear regression model. We included variables of which significance levels were under 0.1 in the univariate model and examined whether these variables were statistically significant at an alpha of 0.05 in the multivariate model.ResultsMean serum 25(OH)D level was 15.4 ng/mL (SD= 6.4). The prevalences of severe deficiency (<10 ng/mL), mild to moderate deficiency (10–<20 ng/mL), and insufficiency (20–<30 ng/mL) of vitamin D in this population were as follows; 17.5%, 63.6%, and 16.5%. Vitamin D intake from food and supplements (β=2.56, p=0.008), season of blood draw (fall vs. spring; β=0.22, p<.0001), skin change in summer sun (a sunburn skin without blisters vs. a mild sunburn that becomes a tan; β=−0.14, p=0.023), and oral contraceptive use (use vs. nonuse; β=0.15, p=0.002) were significantly associated with circulating 25(OH)D levels.ConclusionsWe found that immigrant Filipino women in Korea had high prevalence of deficiency and insufficiency of vitamin D and vitamin D intake, season, skin change and oral contraceptive use were associated with vitamin D status.
Activation of Adrenergic Receptor Subtypes Differentially Regulate Expression of Metabolic Genes in Porcine Adipocytes
Authors: Shin Sunhye , Ajuwon Kolapo M 
Published: November 2023

Pigs adipocytes express mostly the β1 and β2 adrenergic receptors (AR), with limited expression of the β3 adrenergic receptor subtype. However, there is limited understanding of the relative contribution of these receptors to the regulation of important metabolic genes in pig adipocytes. Therefore, this study was conducted with the objective of determining the effect of agonists of β1(dobutamine), β2 (bambuterol), β3 (CGP‐12177‐Hydrochloride) AR and that of α AR (UK14,304). Norepinephrine (NOR) treatment was used to represent non‐specific adrenergic receptor activation. Markers of metabolic activation used include carnitine palmitoyl transferase 1 (CPT1), PPARg coactivator 1a (PGC1a) and deiodinase 2 (DIO2). Significant induction (at least two fold) of expression of these genes was observed with NOR and the b1 agonist, whereas the β2 agonist inconsistently induced these genes. However, the β3 and α AR agonists were ineffective. We further investigated effect of adrenergic receptor blockage with propranolol and inhibition of PKA with H‐89. Both inhibitors blocked NOR and dobutamine effect. These results indicate that pig adipocytes have an inducible, but selective, response to β AR agonists, but are not responsive to α AR agonists. This might indicate the relative importance of these AR subtypes in the regulation of adipocyte metabolism and phenotype in the pig.Support or Funding InformationFunding was received from the Department of Animal Sciences, Purdue University
Positive association between reduced GSH and inadequacy/deficiency of 25‐hydroxy‐vitamin D in obese children
Authors: Jain Sushil K. , Parsanathan Rajesh , Achari Arunkumar E 
Published: November 2023

The deficiency of 25‐hydroxy‐vitamin D [25(OH) VD] has become a world‐wide epidemic. Genetic studies in humans show that the blood levels of 25(OH) VD in response to VD supplements is modulated by the VD regulatory genes. Recent studies report that supplementation with L‐cysteine (LC), a precursor of glutathione (GSH) can upregulate VD regulatory genes [vitamin D binding protein (VDBP), VD‐25‐hydroxylase and vitamin D‐receptor (VDR)]. This study examined the hypothesis that VD deficiency is associated with reduced GSH levels in obese children. Fasting blood was collected from normal subjects enrolled after prior IRB approval. We measured GSH levels by HPLC; 25(OH) VD, insulin and TNF‐α levels using ELISA kits, and glucose using glucose oxidase method. Table shows blood levels of 25(OH) VD and GSH were significantly lower in obese (BMI>30) compared with lean (≤25 BMI) or overweight (≤30 BMI) children. HOMA‐Insulin resistance (IR) and TNF‐α were significantly higher in obese compared with lean or overweight. There was a significant positive correlation between 25(OH) VD and GSH (r=0.24, p=0.04, n=74); IR showed negative association with 25(OH) VD (r=−0.24, p=0.04) and positive association with TNF‐α (r=0.30, p=0.02). GSH‐deficiency induced by glutamate‐cysteine ligase (GCLC) KD, caused down‐regulation of VDBP, VD 25‐hydroxylase and VDR; and pretreatment with LC, a precursor of GSH, and prevented the down‐regulation of VDBP, VD‐25‐hydroxylase and VDR in (FL83B) hepatocytes. Treatment with exogenous TNF‐α (0.2 ng/ml), or GCLC KD caused down regulation of GLUT4 and increase in TNF‐α secretion, which was reversed by LC, in (3T3‐L1) adipocytes. This suggests that deficiency of GSH down‐regulates VD regulatory genes and GLUT4 and thereby reduces circulating 25(OH) VD and induces IR in obesity. Thus, improvement in GSH level represent a novel therapeutic target in preventing/treating 25(OH) vitamin D deficiency and IR in a population at risk for 25(OH) VD‐deficiency (supported by NCCIH RO1 AT007442).Support or Funding Informationsupported by NCCIH RO1 AT007442
Aged Microvascular Networks Display Increased Pericyte Coverage along Capillaries
Authors: Suarez‐Martinez Ariana Diandra , Lane James Hayden , Murfee Walter Lee 
Published: November 2023

While a common characteristic of aging is impaired angiogenesis, defined as the sprouting of capillaries from existing blood vessels, the altered mechanisms remain understudied. An opportunity exists to identify potential mechanisms by comparing cellular characteristics of aged versus adult microvascular networks. A critical cell type involved in capillary sprouting is the vascular pericyte with pericyte‐endothelial cell interactions playing both vessel stabilization (anti‐angiogenic) and angiogenic roles. However, little is known regarding whether pericyte presence is altered in aged tissues. The objective of this study was to compare pericyte coverage along capillaries in adult and aged microvascular networks. Mesentery tissues from adult (9 months) and aged (24 months) male Fischer 344 rats were harvested and immunohistochemically labeled for platelet endothelial cell adhesion molecule (PECAM), and pericyte markers, α‐smooth muscle actin (α‐SMA) or neuron‐glial antigen 2 (NG2). PECAM labeling identified endothelial cells along arterioles, venules, and capillaries across the hierarchy of networks. The percentage of capillaries (diameter <7 mm) with observable SMA positive pericyte labelling in aged networks was significantly increased compared to adult networks (Aged = 90.9% vs. Adult = 78.1%; p<0.05). Similarly, NG2 coverage of capillaries was also significantly increased in aged networks compared to adult networks (Aged = 94.9% vs. Adult = 76.6%; p<0.005). These results suggest that aged microvascular networks are characterized by increased pericyte coverage and motivate a new hypothesis for aging research that impaired angiogenesis in aged tissues is associated with increased vessel stabilization by vascular pericytes.Support or Funding InformationNIH R01AG049821, NIH P20GM103629
Myocardial Vascular Protection in Hibernating Woodchucks
Authors: Zhang Jie , Vatner Dorothy E. , Guers John , Vatner Stephen F 
Published: November 2023

True mammalian hibernation is a remarkable and natural mechanism to change the body's metabolism to meet the ravages of winter, when the animals do not eat or drink. At one point it was thought that these protective mechanisms related only to metabolism of fat and muscle including thermogenic protection. The goal of this study was to elucidate how the novel mechanisms elicited in hibernation can protect the heart from myocardial ischemia in an animal model with no coronary artery disease. Accordingly we compared the effects of myocardial infarction (MI) induced by permanent coronary artery occlusion (CAO) for 2 months in woodchucks in summer, when they were not hibernating, and in winter when they were. During hibernation they were markedly protected, p<0.05, from myocardial ischemia with reduced infarct size (37± 2.3% in winter, vs 47±3.1% in summer) and mortality (14% in winter vs 52% in summer) and preserved cardiac function as assessed by left ventricular ejection fraction (58±3.3% in winter, vs 42±3.3% in summer). The only way this might be possible in the face of permanent CAO would be if angiogenesis/arteriogenesis developed in the hibernating hearts following CAO. Indeed this is what was observed and determined by Ki67 + endothelial cell staining (0.60± 0.13% in winter vs 0.09±0.02% in summer). We then identified the vascular growth factors (VEGF, cTGF, PDGF, and EGR1) that were upregulated in the hibernating woodchuck heart, including nitric oxide synthase and CREB. Thus, natural mammalian hibernation induces marked cardioprotection through induction of angiogenesis/arteriogenesis.Support or Funding InformationThis study was supported by NIH funding R01HL130848.
Taurine Supplementation Improves Arterial Pressure Control Function after Cardiac Ischemia/Reperfusion via Systemic Inhibition of the Renin‐Angiotensin System in Adult Female Rats Perinatally Depleted of Taurine and Supplemented with High Sugar
Authors: Roysommuti Sanya , Kulthinee Supaporn , Wyss James Michael 
Published: November 2023

Perinatal taurine depletion followed by a high sugar diet exacerbates cardiac injury and arterial pressure dysregulation after ischemia/reperfusion (IR), and this effect is blunted by taurine supplementation or inhibition of renin‐angiotensin system. This study tests the hypothesis that taurine supplementation improves arterial pressure control in this model via systemic inhibition of renin‐angiotensin system overactivity. Female Sprague‐Dawley rats were fed normal rat chow with tap water alone (control, C) or tap water containing 3% beta‐alanine (taurine depletion, TD) from conception to weaning. Female offspring were fed the normal rat chow and drank 5% glucose in tap water (CG and TDG) or tap water alone (CW and TDW) throughout the study. One week before surgery, half of rats in each treatment were supplemented with 3% taurine in tap water (CW+T, CG+T, TDW+T, and TDG+T). At 7–8 weeks of age, blood chemistry and hemodynamic parameters were studied in conscious and anesthetized rats after cardiac IR induction and in untreated Sham control rats. Body and heart weights, plasma electrolytes, plasma creatinine, and blood urea nitrogen were not significantly different among the nine groups. However, plasma angiotensin II concentrations were markedly and significantly elevated in TDG compared to all other groups (Sham, 33.9 ± 4.4 pg/ml; CW, 20.2 ± 2.3 pg/ml; CW+T, 24.4 ± 4.3 pg/ml, CG, 20.8 ± 2.9 pg/ml; CG+T, 20.2 ± 2.3 pg/ml; TDW, 22.6 ± 2.5 pg/ml; TDW+T, 15.1 ± 1.0 pg/ml; TDG, 61.1 ± 7.6 pg/ml (p < 0.05 to all other groups); TDG+T, 32.8 ± 4.7 pg/ml). After cardiac IR, mean arterial pressure significantly increased in all IR groups, compared to their corresponding values before IR. Further, in the TDG compared to all other groups, baroreflex sensitivity was markedly and significantly depressed and sympathetic nerve activity was significantly increased. Power spectral analysis of renal nerve activity indicated a significant increase in renal renin release only in the TDG compared to all other groups, though renal firing frequency increased in CG, TDW, TDW+T, TDG, and TDG+T groups. The adverse effects of cardiac IR on arterial pressure control, renin release, and plasma angiotensin II were improved by short‐term taurine supplementation. The present study demonstrates that in adult female rats perinatally depleted of taurine followed by a high sugar diet, taurine supplementation improves the adverse effects of cardiac IR on arterial pressure control via inhibition of systemic renin‐angiotensin system overactivity.Support or Funding InformationThis work was supported by Khon Kaen University, Khon Kaen, Thailand.
Elevated Sympathetic Nerve Activity Mediates Increases in Large Central Elastic Artery Stiffness Independent of Changes in Blood Pressure in Humans
Authors: Holwerda Seth William , Credeur Daniel P. , DuBose Lyndsey E. , Luehrs Rachel E. , Schwartz Christopher E. , Fadel Paul J. , Pierce Gary L. 
Published: November 2023

Recent evidence suggests that elevated sympathetic nerve activity (SNA) may increase large central elastic artery stiffness (i.e., carotid, aorta), a robust independent predictor of cardiovascular disease. However, experimental manipulations involving increased (e.g., handgrip exercise) or decreased (e.g., ganglionic blockade) SNA in humans have also evoked concomitant changes in arterial blood pressure (BP) making interpretation difficult. Therefore, we tested the hypothesis that acute elevations in SNA increase central artery stiffness independent of BP. First, in 7 young healthy men (20 ± 1 yrs; 26 ± 1 kg/m2), carotid artery compliance was assessed at baseline and during a moderate level of lower body negative pressure (LBNP, −45mmHg), a stimulus known to significantly increase SNA without major changes in BP. Next, carotid‐femoral pulse wave velocity (PWV), the gold standard assessment of aortic stiffness, and resting muscle SNA (MSNA) were assessed in a larger sample of healthy individuals (n=30; 37 ± 3 yrs; 11 women) and correlated. During LBNP, baroreflex‐mediated increases in heart rate were observed (BL: 59 ± 3 vs. LBNP: 80 ± 5 bpm, P<0.05), but mean BP was unchanged (BL: 79 ± 1 vs. LBNP: 81 ± 1 mmHg, P>0.05). Carotid artery compliance was significantly reduced during LBNP compared with baseline (BL: 1.15 ± 0.11 vs. LBNP: 0.71 ± 0.1 mm2/mmHg×10−2, P<0.05) in addition to reductions in brachial artery compliance (BL: 0.1 ± 0.03 vs. LBNP: 0.07 ± 0.02 mm2/mmHg×10−2, P<0.05). In the larger sample, carotid artery compliance was moderately associated with resting MSNA (R=−0.374, P=0.055); however, there was a stronger association between carotid‐femoral PWV and resting MSNA (R=0.583, P<0.01) that persisted after adjusting for BP and sex (R=0.471, P<0.01). Together, these preliminary data suggest that SNA acutely increases large central elastic artery stiffness in humans independent of changes in BP, and that tonically elevated resting SNA may contribute to higher large central elastic artery stiffness.Support or Funding InformationNIH T32 HL007121, P01HL014388, U54TR001356 and American Heart Association 13SDG143400012