bluuebunny/crossref_metadata_2025_split huggingface dataset:
Resveratrol‐Enriched Rice Protects Human Skin against UVB‐Induced Photoaging
Authors: Lee Taek Hwan , Subedi Lalita , Wahedi Hussain Mustatab , Park Yong Un , Kim Sun Yeou 
Published: November 2023

Ultraviolent radiation can cause skin photoaging, skin wrinkle and pigmentations. Synthetic cosmaceuticals as well as medicines have number of side effects as well as drawbacks so natural therapies are the best way of protecting human skin and looking young and smart. Genetically engineered Resveratrol‐enriched rice (RR) has been reported to have excellent anti‐obesity and depigmenting effects in human skin however its effect in UVB induced skin aging was not studied yet. In this study, we evaluated the effects of normal rice (NR), resveratrol‐enriched rice (RR), and resveratrol (R) on ultraviolet B (UVB)‐irradiated human dermal fibroblasts (HDFs) and reconstructed skin tissue to determine the therapeutic potential of these agents in skin wrinkling and skin photoaging. We measured the cellular levels of procollagen type I (PIP‐1) and matrix metalloproteinase (MMP)‐1 using ELISA in NHDF cells after UVB irradiation. UVB‐irradiated NHDF cells that were treated with NR, RR, and R exhibited higher PIP‐1 levels and lower MMP‐1 levels than untreated cells. Among the treatments, RR was found to have the maximum potential to prevent skin damage in both, for MMP‐1 inhibition as well as PIP induction. Taken together, our findings demonstrated that the anti‐wrinkle properties of RR might be superior to those of R or NR alone. Additionally, RR possesses anti‐skin photoaging effects, via downregulating the MMP‐1 levels and upregulating the pro‐collagen production in UVB‐irradiated reconstructed skin as well. In conclusion, RR may provide a non‐toxic and convenient means of preventing UVB‐induced skin wrinkles and related diseases.Support or Funding InformationThis work was supported by a grant from the Next‐Generation BioGreen 21 Program (No. PJ01118803), Rural Development Administration, Republic of Korea
Overexpression of Tbx20 in Adult Cardiomyocyte Promotes Myocyte Proliferation and Improves Cardiac Function post Myocardial Infarction
Authors: Xiang Fuli , Guo Minzhe , Yutzey Katherine 
Published: November 2023

BackgroundAdult mammalian cardiomyocytes (CM) have the potential to proliferate, but this is not sufficient to compensate for the massive loss of functional CMs after myocardial infarction (MI). During embryonic heart development, the transcription factor Tbx20 is required for CM proliferation, and Tbx20 overexpression (Tbx20OE) promotes fetal characteristics in adult CMs when initiated before birth in mice. We hypothesize that Tbx20OE, when induced in adult CMs after injury, improves cardiac function and repair via dedifferentiation and cell cycle re‐entry of CMs.Methods and ResultsTbx20OE was induced in inducible CM‐specific Tbx20 overexpressing adult mice via tamoxifen. Increased CM proliferation and fetal characteristics were found in Tbx20OE hearts compared to controls without affecting cardiac function and morphology 4 weeks after Tbx20 overexpression at baseline. However, Tbx20OE in adult CM after MI significantly improved cardiac function and infarct size, and decreased myocardial hypertrophy 4 weeks post‐MI. Improved cardiac repair as indicated by increased capillary density and CM proliferation was also observed in border zone of Tbx20OE hearts compared to controls. Expression of proliferation activators (cyclin D1, E1, and IGF1) and fetal contractile proteins (ssTNI, βMHC) mRNA was increased, while negative cell‐cycle regulators (p21, Meis1) were decreased, in Tbx20OE hearts compared to controls under both baseline and MI conditions. Interestingly, multiple pro‐proliferation pathways including Akt, YAP and BMP signaling were activated in Tbx20OE adult heart at baseline. And we found p21, Meis1 and Btg2, act as direct downstream targets of Tbx20 in CM proliferation.Conclusion(sIn conclusion, Tbx20OE in adult CM promotes cell proliferation via regulating multiple pro‐proliferation pathways and directly impair cell‐cycle repressor gene p21, Meis1 and Btg2. Overexpressing of Tbx20 in adult CM improves cardiac function and repair in mice when induced post‐MI.Support or Funding InformationAmerican Heart Association postdoc fellowship 15POST22060001
A Novel Freely Moving Animal Based Blood Pressure, ECG, and Dual Body Temperature Telemetry System for Group Housed Mice in Social Context
Authors: Knot Harm Johan , Lee Dexter 
Published: November 2023

Traditional rodent blood pressure (BP) monitoring required single housing, a known stressor for rodents. We developed a microprocessor based long range wireless telemetry system based on the Stellar™ technology with internal memory that allows rodents to live in groups, interact, exercise and be housed in large enriched environments. BP or ECG is recorded with a solid‐state sensor along with core temperature and 3D activity. Heart rate was derived from BP and/or ECG in the Biopac AcqKnowledge 4.4.1 software.It is well established that rodent behavior is strongly influenced by social interaction. Moreover, spontaneous hierarchies develop in group housed animals and cardiovascular parameters such as heart rate and blood pressure reflect these conditions. Since animal experimentation most notably in neuroscience and behavior studies gravitate towards group housed colonies also for sake of animal welfare new technologies are needed to allow traditional measurements to be done in these new more refined research environments. Moreover, in the case of metabolic studies where animals tend to huddle in groups when they sleep, a similar adaptive behavior needs to be taken into account when calculating energy expenditure in nutritional and diabetes/obesity studies.In order to objectively validate this system we implanted 5 male mice of ca. 20 g. After 8 days of recovery the animals entered an exploratory study to compare fidelity and accuracy of the novel solid‐state microtipped pressure lead (450 micron) based wireless implant and BP was recorded for 10s every 15 min for 4 weeks sampled at 200Hz. The BP responses were compared to a control group of 5 animals implanted with a similar conventional implant from a competitor sampled for 5s every minute at 500Hz equiped with a fluid‐filled catheter. Mean dark phase arterial pressures (MAP) at 14 days in the Stellar group were 134 ± 31 mmHg at a Heart rate (HR) of 544 ± 67 BPM versus 127 ± 9 mmHg at a HR of 545 ± 24 in the control group. Further studies on core body temperature are progressing and will be presented.We conclude that there are no significant differences in quantitative blood pressure responses between the Stellar digital telemetry device versus a leading analog competing device while being able to record from up to 5 different animals without cross‐talk. We also conclude that the short scheduled recordings used for the Stellar device produced equivalent MAP values at better (less) data economy while significantly prolonging implant battery life, thus extending the possible study length as needed for behavioral monitoring in group housed animals to several months.
Internalized silver nanoparticles alter ion transport and hemoglobin spectrum in human red blood cells
Authors: Alla Praveen Kumar , Lauf Peter K , Pavel Ioana , Paluri Arathi , Markopoulos Marjorie , Yaklic Jerome , Adragna Norma C. 
Published: November 2023

In the last decades, numerous studies on the industrial and biomedical applications of nanomaterials (NMs) have emerged. For instance, the effect of silver nanoparticles (AgNPs) on red blood cell (RBC) hemoglobin (Hb) was measured by Raman tweezers spectroscopy on single live cells. The findings show that AgNPs of diameter > 100 nm cause irreversible changes in the Hb heme's conformation from the normal oxy‐ to the deoxy‐state, i.e. from the R (relaxed)‐ to the T (tense)‐state. However, less is known regarding the NMs effects at the level of cellular function. Here, we report on the effect of internalized AgNPs on ion transport in human (H) RBCs. Rubidium influx and K concentration were determined in the presence and absence of 100–150 μg/mL negatively charged 10 nm AgNPs. Furthermore, the Hb spectrum under the same experimental conditions as the ion transport studies was also measured. Internalization of AgNPs in RBCs was determined by integration of enhanced dark field optical microscopy and hyperspectral imaging in a CytoViva® equipment. Our preliminary findings indicate that the tested internalized AgNPs inhibit Rb influx and deplete the cells from K by mechanisms currently under investigation. In addition, the AgNPs altered the absorbance for the Hb peaks and showed an additional broad shoulder between 594.1 and 658.8 nm. The changes in the Hb spectrum in the presence of AgNPs could be interpreted as the AgNPs causing an increase in the oxidized form of Hb, i.e. MetHb. Further studies are on the way to establish whether there is a correlation between the changes in Hb oxidative state and the alterations in cellular ionic composition induced by the AgNPs tested.Support or Funding InformationSupported by National Science Foundation and Wright State University Foundation
Behavioral Comorbidities in Dextran Sulphate Sodium (DSS) Colitis, an animal model of Inflammatory Bowel Diseases
Authors: Nyuyki‐Dufe Kewir , Cluny Nina L , Sharkey Keith A , Swain Mark G , Pittman Quentin J. 
Published: November 2023

Inflammatory Bowel Diseases (IBD), which include Crohn's disease and ulcerative colitis represent a group of incurable lifelong diseases affecting about 0.67% of the Canadian population (2012) and severely impacts the health‐related quality of life through ongoing debilitating symptoms like pain, gastrointestinal dysfunction as well as behavioral comorbidities like anxiety, depression, fatigue and cognitive impairment. Depression and anxiety are prevalent in individuals with IBD at a rate that outpaces the general population thereby substantially increasing the burden of the disease, as well as economic cost of managing it. Although clinical surveys and population studies have established a strong relation between IBD, depression and anxiety disorders, our knowledge of CNS changes is limited. We therefore investigated these comorbidities in a mice model of IBD with similarities to Ulcerative colitis, caused by administration of Dextran sulphate sodium (DSS) in drinking water for 5 days. In male and female mice, DSS treatment caused increased increased brain excitability, revealed by a decrease in seizure onset times after intraperitoneal administration of 25mg/kg body weight of Kainic acid; this was positively correlated with the intensity of inflammation only in males. Moreover, both sexes showed an increased anxiety‐related behavior on the elevated plus‐maze (EPM). We assessed pain levels, because they may influence behavioral response; only male mice were hyperalgesic when tested on the hotplate for thermal pain sensitivity indicating that altered behavioral responses cannot be entirely attributed to an interference with a movement brought about by pain. Further studies mapping the CNS pathways integral to the above changes will reveal novel mechanisms as to how peripheral inflammation results in changes in central immune‐mediated affective behaviors.Support or Funding InformationThis work is supported by Alberta Innovates‐Health Solutions (AI‐HS) and Canadian Institutes of Health Research team grants, and by the Hotchkiss Brain Institute and AI‐HS personnel support awards.
A role of hemodynamic stress in carotid stenosis; a study using computational fluid dynamic analyses
Authors: Fukuda Shunichi , Shimogonya Yuji 
Published: November 2023

BackgroundIt is difficult to predict cervical carotid stenosis because our current understanding of its risk factors is incomplete. Several reports suggested that carotid arterial geometry is an independent risk factor for carotid atherosclerotic disease in association with disturbed flow. However, there are few reports indicating a quantitative analysis in hemodynamic distributions of carotid stenosis. Thus, we examined here hemodynamic involvement in carotid stenosis using computational fluid dynamic (CFD) techniques.MethodsDistributions of time‐averaged wall shear stress (TAWSS), time‐averaged WSS gradient (TAWSSG), oscillatory shear index (OSI), gradient oscillatory number (GON) proposed by us, and transverse wall shear stress (transWSS) in stenotic (n=11) and non‐stenotic (n=5) cervical carotid arteries were examined using ANSYS‐CFX software. Patient‐specific arterial geometries and inflow velocities were obtained from 3‐dimentional CTA images and carotid ultrasound Doppler examinations.ResultsTAWSSG in stenotic arteries tended to be higher compared with non‐stenotic arteries (p=0.157). There was a tendency that transWSS and GON, metrics for disturbed flow, were higher in stenotic vessels than non‐stenotic vessels (p=0.112 and 0.234, respectively). Moreover, there were significant increases in TAWSSG and transWSS in severe stenotic arteries (more than 75% in area) compared with non‐stenotic arteries (Figure 1; p=0.0143 and 0.0274, respectively).ConclusionsThe data suggest that CFD analyses in distributions of WSS and disturbed flow may serve to clarify new risk factors for carotid stenosis. We are planning multi‐institutional clinical trial about the issue.Support or Funding InformationThis research was supported by AMED‐CREST, AMED.
Effects of various natural sweeteners on insulin resistance, inflammation and liver steatosis in a rat model of diet‐induced obesity
Authors: Valle Marion , St‐Pierre Philippe , Pilon Geneviève , Anhê Fernando Forato , Varin Thibault , Marette André 
Published: November 2023

BackgroundThe detrimental effect of refined sugars on health has been the subject of many investigations. However, very few studies have looked at the long‐term beneficial impact of natural sweeteners in a context of obesity.ObjectiveThe objective of this study was to compare the metabolic responses following the chronic ingestion of refined simple sugars (sucrose and fructose) to that of various natural sweeteners in a diet‐induced obese insulin‐resistant rat model.MethodsRats were fed a high‐fat high sucrose diet (HFHS) for 8 weeks and received daily gavage with a solution of equivalent amount of total carbohydrates from either sucrose, fructose, maple syrup, molasses, brown rice syrup, agave syrup, corn syrup, or honey. A group fed a standard chow diet receiving daily gavage with the sucrose solution was used as a control. Weekly body weight and food intake were assessed. At week 7, glucose tolerance was evaluated by an oral glucose tolerance test (OGTT), while insulin sensitivity was determined using the HOMA‐IR index at 8 weeks. Nonalcoholic fatty liver disease (NAFLD) was assessed by hepatic triglyceride (TG) content and liver inflammation.ResultsDaily gavage with the different natural sweeteners did not lead to differences in food intake or body weight gain. During the OGTT, similar glycemic responses were observed across the different treatment groups. However, the insulin excursions were lower in the maple syrup treated animals suggesting improved insulin sensitivity. Assessment of insulin resistance by calculation of the HOMA‐IR index further revealed that all natural sweeteners except corn syrup significantly improved insulin sensitivity, when compared to sucrose treatments. Furthermore, whereas hepatic TG content was reduced in maple syrup, molasses and agave syrup treated rats, there was an increased TG accumulation in the brown rice and corn syrup treated rats. Hepatic inflammation, as revealed by increased IL‐1B levels in obese rat liver, was also reduced to various extents by gavage of molasses, agave syrup, maple syrup and corn syrup.ConclusionSeveral natural sweeteners used in this study were found to improve insulin sensitivity and to reduce NAFLD as compared to an equivalent amount of sucrose in diet‐induced obese rats. Among the natural sweeteners, maple syrup, molasses and agave syrup appear to exert the most consistent beneficial effects on multiple metabolic health endpoints, suggesting that consumption of those natural sweeteners is a healthier alternative to simple refined sugar.Support or Funding InformationThis project was supported by Agriculture and Agri‐Food Canada from the Agricultural Innovation program, a federal‐provincial‐ territorial initiative in Canada, and with the participation of the Federation of Quebec Maple Syrup Producers.
Oral L‐Tyrosine Supplementation Augments Cutaneous Vasoconstriction to Whole Body Cooling
Authors: Smaller Kevin A , Lang James A 
Published: November 2023

Healthy older adults exhibit a blunted cutaneous vasoconstriction (VC) response to cold exposure, which increases their susceptibility to rapid heat loss and hypothermia. We hypothesized that oral supplementation of L‐tyrosine, the primary substrate for catecholamine biosynthesis, would augment the VC response to gradual whole‐body cooling (Tsk = 30.5 °C) in older adults. Eleven young (Y = 24±1 years) and eleven older (O = 68±4‐‐‐‐‐‐ years) participants completed a randomized, double‐blinded, placebo‐controlled, cross‐over study consisting of two visits separated by >3 days. At the beginning of each visit, participants ingested either 150 mg/kg L‐tyrosine or placebo. An hour after consumption, whole‐body cooling commenced, causing a gradual decline in skin temperature from 34 to 30.5 °C over a 30 minute period. Laser Doppler flux (LDF) was measured at the ventral forearm and cutaneous vascular conductance (CVC) was calculated as CVC = LDF/mean arterial pressure and expressed as a percent change from baseline (%ΔCVC). Two minutes of static handgrip exercise (35% MVC) followed by 3 minutes of post‐exercise ischemia was implemented before and toward the end of the cooling bout. No changes in blood pressure or heart rate were identified with tyrosine supplementation. However, the VC response to whole‐body cooling was blunted in older adults (Placebo: Y = 29±3; O = 21±5 %ΔCVC) and this was augmented with tyrosine supplementation (Tyrosine: Y = 37±5; O = 31±4 %ΔCVC; p<0.05). These results indicate that oral L‐tyrosine supplementation restores the VC response to whole‐body cooling in older adults. This suggests that L‐tyrosine may be a limiting factor in the full expression of the cutaneous VC response and supplementation may help maintain body core temperature during cold exposure particularly in an older population.Support or Funding InformationDMU IOER Grant 03‐14‐01
Bicarbonate secretion in human small airways
Authors: Shamsuddin A K M , Quinton Paul M 
Published: November 2023

Cystic Fibrosis (CF) pathology is attributed to a basic defect in epithelial anion transport. The loss of bicarbonate (HCO3−) transport in CF plays a critical role in pathogenesis by interrupting the normal formation and release of mucins in exocrine tissues as in pancreas, liver and intestines in CF, we do not know whether HCO3− secretion occurs in normal human native small airways, the most prevalent site of morbidity and mortality in CF. Using our recently developed mini‐Ussing chamber system to determine the properties of HCO3− transport in freshly dissected human airways (diameter ≈ 2.0 mm). We assayed HCO3− transport by measuring the transepithelial potential, conductance and equivalent short circuit current with bilateral 25 mM NaHCO3− plus 125 mM NaGlu in presence of luminal amiloride. Under these conditions since the only major transportable anion present was HCO3−, we took the short‐circuit current to be a direct measure of HCO3− transport in small airways. Applying selective agonists and/or inhibitors, we show that human native small airways constitutively secrete HCO3−, and could be further stimulated agonists mediated by cAMP (adrenergic) and Ca2+ (purinergic) and respectively inhibited by selective antagonists. These results suggest at least two pathways for HCO3− secretion, one dependent on Cystic fibrosis transmembrane conductance regulator (CFTR) and another dependent on a calcium‐activated chloride channel (CaCC), that secrete HCO3− into the airway luminal surface liquids, to critically support the discharge of mucins and maintain airway surface liquid pH for optimal defense and hygiene of small airways. By analogy with other organs in CF, failure to secrete HCO3− likely results poor mucociliary and pathogen clearance and thus should be seen a new target for therapy in CF and possibly other airway diseases.Support or Funding InformationSupported by the Nancy Olmsted Trust, the Cystic Fibrosis Foundation and Cystic Fibrosis Research, Inc.
Enhanced Hepatic Insulin Sensitivity With Inhibited Gluconegenesis In Native High Altitude Rats
Authors: AL‐Hashem Fahaid Hassan , Al‐Musa Hassan 
Published: November 2023

Backgroundhigh‐altitude (HA) populations had lower basal glucose levels as compared to low altitude (LA) natives and the mechanism(s) behind this is lacking. Interestingly, insulin, 5′ adenosine monophosphate‐activated protein kinase (AMPK) are able to restrain hepatic gluconeogenesis by inhibiting expression of Glucose 6‐phosphatase (G6Pase) and Phosphoenolpyruvate carboxykinase (PEPCK).AimTo test the hypothesis that HA have lower rate of hepatic gluconeogenesis due to enhanced insulin signaling and/or activation of hepatic AMPK under both basal and glucose stimulation.MethodsMale rats of match aged, diet, genetic background and native to LA and HA areas were used. Fating plasma glucose and insulin levels were determined after which i.p glucose, pyruvate and insulin tolerance tests (IPGTT, IPPTT and IPITT, respectively) were carried out. Under basal or after insulin stimulation, liver samples were collected and real‐time reverse transcription‐PCR (qRT‐PCR) and western blotting were carried out.ResultsHA rats had stable basal insulin levels with significant lower basal glucose levels and Insulin resistance index (HOMA‐IR) with enhanced glucose clearance and insulin tolerance. Gluconeogenesis was significantly inhibited in HA rat as evident by decreased glucose production after IPPTT. HA rats had inhibited lower protein levels of Glucose transporter 2 (GLUT‐2) and G6Pase and PEPCK under basal and insulin stimulation. Concomitantly, HA rats had had higher levels of the following antibodies p‐IRS(tyr 612), p‐Akt and p‐FOX01 and lower levels of p‐mTOR/p‐70S6K/P‐IRS(ser307) suggesting enhanced hepatic insulin signaling. however, levels of AMPK, p‐AMPK and AS160 were not significantly different between LA and HA rats.In conclusion, our novel data is the first to show that HA native rats exhibit lower glucose levels and HOMA‐IR, at least, due to inhibited gluconeogenesis which is mediated through enhanced hepatic insulin but not AMPK signaling.