bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nitric oxide ameliorates muscular dystrophy
Authors: Danialou Gawiyou 
Published: November 2023

IntroductionDuchenne muscular dystrophy (DMD) is a lethal, X‐linked disorder associated with dystrophin deficiency that results in chronic inflammation, sarcolemma damage, and severe skeletal muscle degeneration. Effective drug therapy for reducing or delaying the skeletal muscle weakness and necrosis could be a great hope for individuals suffering from DMD. Here we hypothesized that the early treatment of mdx neonatal mice with L‐arginine could ameliorate muscular dystrophy.MethodsSeven days old animals were treated IP daily with 800 mg/kg of L‐arginine (L‐arg) or saline (control group) for six weeks. The hind limb skeletal muscle, the Tibialis Anterior (TA) was investigated. The following parameters were evaluated: the force generated, muscle resistance to mechanical stress, the level of centronucleation, detection of utrophine by immonostaining and western blot, creatine kinase (CK) activity and, nitric oxide (NO) production.ResultsOur results show that: 1) TA weight and the percentage of centronucleation in L‐arg treated animals were significantly lower than in control animals despite the fact that body weights were not different; 2) L‐arg improved TA ability to resist injury caused by high‐stress contractions; 3) CK level was two time higher in control animals compared to L‐arg treated mice, however, this difference was not statistically significant; 4) NO production was significantly higher in L‐arg treated animals; 5) there was no evidence that the improvements observed in L‐arg treated mice were associated with utrophin upregulation.ConclusionOur data strengthen the usefulness of L‐Arginine as a powerful pharmacological tool in Duchenne muscular dystrophies. However, the improvements observed were not associated with utrophin upregulation.Support or Funding InformationMuscular Dystrophy Association (MDA)Canadian Institutes of Health Research (CIHR)
Reduced Levels of Thyroid Receptor Interacting Protein 13 Prevents Recovery of Tubular Epithelial Cells following Renal Ischemia‐Reperfusion Injury
Authors: Pressly Jeffrey D. , Hama Taketsugu , Regner Kevin R. , Park Frank 
Published: November 2023

Damage to renal tubular epithelial cells by genetic, environmental, or biological insults can initiate complex signaling mechanisms that promote kidney repair and functional recovery. Recently, there is accumulating evidence that chromatin damage and the subsequent signaling repair mechanisms in the kidney can play a pivotal role in the recovery of the injured tubular epithelial cells following a biological stress. In this study, we demonstrate that thyroid receptor interacting protein 13 (TRIP13) is a critical modulator of tubular epithelial cell repair following ischemia‐reperfusion injury (IRI), a common type of renal stress. Transcript profiling demonstrated Trip13 mRNA to be robustly increased by 7.4 ± 0.3 (P<0.001; n=3) and 4.3 ± 2.0 (P<0.01; n=3) fold during the initial 24 and 72 hour period, respectively, following IRI. To further understand the role of TRIP13 in recovery to renal stress, unilateral ischemia‐reperfusion injury (IRI) was performed on Trip13Gt/Gt hypomorphic mice. After 168 hours following the IRI procedure, the wild‐type Trip13+/+ mice kidneys exhibited a significantly lower (P<0.05) number of damaged outer medullary renal tubules (38.7 ± 8.0%; n=5) compared to the hypomorph Trip13Gt/Gt mouse kidneys (95.1 ± 1.4%; n=4). This effect was associated with a higher number of outer medullary collecting ducts as determined by AQP‐2 immunostaining in the WT (174 ± 16.7; n=5) than the hypomorph kidneys (69.0 ± 12.5; n=4). Histological analyses demonstrated significantly higher percentage of TUNEL‐positive cells, a marker of apoptosis, in the outer medulla by 2.4‐fold (P<0.05; n=3) in the Trip13Gt/Gt mouse kidneys compared to the wild‐type Trip13+/+ kidneys (n=6). This was also associated with significantly exaggerated levels of p53 and cleaved caspase‐7 by 45% and 170% (P<0.05), respectively, in Trip13Gt/Gt mouse kidneys compared to Trip13+/+ mouse kidneys (n=6). To evaluate whether inhibition of the p53 pathway could restore the tubular recovery following unilateral IRI, we performed a subsequent study in the presence of a p53 selective inhibitor, α‐pifithrin. Administration of α‐pifithrin in wild‐type Trip13+/+ compared to hypomorphic Trip13Gt/Gt kidneys resulted in a markedly reduced number of damaged outer medullary tubules (8.1 ± 0.6%; n=4 and 16.8 ± 1.1%; n=4, respectively) compared to their untreated control mouse kidneys (38.7 ± 8.0%; n=5 and 95.1 ± 1.4%; n=4, respectively). In all, this study suggests that insufficient TRIP13 levels increased the susceptibility of damaged renal tubular epithelial cells to progress towards cell death following ischemia‐reperfusion injury by exacerbating the p53 response pathway.Support or Funding InformationThis study was funded by NIH RO1‐DK90123, and UTHSC seed grant program.
Therapeutic Potential of AICAR in Attenuating Obesity‐Induced Metabolic, Liver and Kidney Disease
Authors: Borgeson Emma , Borgeson Ville Wallenius , Godson Catherine , Sharma Kumar 
Published: November 2023

Study ObjectiveObesity is a risk factor for organ inflammation, diabetes, and kidney disease. Here we evaluated the therapeutic potential of AICAR (an AMPK activator) in obesity‐induced metabolic, kidney and liver disease with High‐Fat‐Diet (HFD) in wild type and adiponectin‐deficient mice. We also correlate our findings to human pathophysiology, by examining human tissue responses to AICAR ex vivo in a proof of concept study.MethodMale C57BL/6 or Adiponectin−/− mice were fed a standard (10% fat) or HFD (60% fat) diet for 12 wks. HFD induced obesity and CKD, as evident by increased albuminuria. Vehicle or AICAR (500 mg/g) was given intraperitoneal as interventional therapeutics 3 times weekly, between wk 5–12. Furthermore, omental adipose tissue biopsies were isolated from obese (BMI 35–50), non‐diabetic female bariatric surgery patients (n=4). The adipose explants were incubated ex vivo with vehicle or AICAR (1 mM) for 6 hours at 37 °C, after which leukocytes were characterized by flow cytometry.ResultsInterventional AICAR treatment protected against obesity‐induced kidney disease, liver steatosis and improved insulin sensitivity in mice. Adipose inflammation is a key driver of obesity‐induced pathophysiology. AICAR attenuated adipose inflammation, by shifting MΦ phenotype from pro‐inflammatory M1 (CD11c+) to anti‐inflammatory M2 (CD206+), while reducing the percentage of CD8+ T‐cells, which correlated with reduced TNF‐α production and increasing adipose pAMPK levels. Interestingly, AICAR reduced interstitial adipose fibrosis, but enhanced omental capsular fibrosis. AICAR‐mediated protection was adiponectin independent, as protection was observed in both obese wild‐type and adiponectin−/− mice. In omental adipose tissue explants isolated from obese patients, AICAR promoted a ‘pro‐inflammatory’ to ‘anti‐inflammatory’ MΦ phenotype switch, which correlated with a reduction in TNF‐α.ConclusionIn conclusion, these data support a novel therapeutic paradigm for using AICAR to promote metabolic health and protect against obesity‐induced systemic pathophysiology, e.g. liver and kidney disease.Support or Funding InformationFinancial support was obtained from the National Institute of Health and Science Foundation Ireland, and EB is a recipient of grants from the Marie Curie International Outgoing fellowship (IOF‐GA‐2011‐301803) and the Swedish Research Council.
Chemerin/ChemR23 system plays crucial role upon vascular insulin signaling in db/db mice
Authors: Neves Karla Bianca , Lobato N. S. , Cat A Nguyen Dinh , Lopes R.A.M. , Hood K. Y. , Oliveira A. M. , Montezano A. C. , Touyz R. M. , Tostes R. C. 
Published: November 2023

The adipokine chemerin and its receptor, chemokine‐like receptor 1 (ChemR23), influence major aspects of the metabolic syndrome, including adipogenesis and insulin sensitivity in adipocytes and skeletal muscle cells. Considering that chemerin impairs vascular reactivity and that amongst its many actions, insulin also influences vascular function, we postulate that chemerin impairs vascular insulin signaling via PI3K/Akt and that ChemR23 antagonism improves insulin signaling in diabetic mice. Lean (db/m) and obese and diabetic (db/db) mice were treated for 03 weeks by oral gavage with CCX 832 (ChemR23 antagonist). Mesenteric arteries, aorta and perivascular adipose tissue (PVAT) were isolated to perform functional and molecular experiments. Plasma levels of chemerin and body weight were increased in db/db mice compared to their counterpart controls db/m. However, db/db mice treated with ChemR23 antagonist (CCX 832) exhibited a slightly decrease in body weight. ChemR23 antagonism in db/db mice partially reversed decreased insulin‐induced vasodilatation (mesenteric resistance arteries; Emax: db/m: 60.75±4.09; db/db: 40.84±2.38; db/m + CCX832: 67.87±8.93; db/db + CCX832: 50.17±3.84). CCX 832 prevented the rise in glucose and insulin levels observed in db/db mice. In aorta, there was a decrease in PI3K, Akt and IRS1 phosphorylation as well as in GLUT4 protein expression in db/db mice. Treatment of animals with ChemR23 antagonist increased GLUT4 protein expression and IRS1 phosphorylation, with a trend to augmented PI3K and Akt phosphorylation. db/db mice exhibited increased vascular ROS generation, which was decrease by CCX 832. M2 macrophages markers mRNA expression (IL‐10 and CD206) in PVAT was decreased in db/db mice and treatment with ChemR23 antagonist prevented this effect. However, no changes were observed in M1 macrophages markers mRNA levels. CCX 832 also blunted the rise in MCP‐1 and TNF‐α gene expression in PVAT from db/db mice. CCX 832 increased plasma and PVAT adiponectin levels, which were reduced in db/db mice. In conclusion, ChemR23 antagonism by CCX 832 (1) decreases body weight of db/db mice; (2) partially restores vascular function in db/db mice; (3) improves insulin signaling in aorta from diabetic mice; (4) decreases the inflammatory profile of adipocytes from db/db mice; (5) decreases vascular oxidative stress in db/db mice. These findings indicate that chemerin/ChemR23 axis may contribute to inflammation, oxidative stress and decreased vascular insulin signaling in diabetes. Our study may contribute to a better understanding of the role of chemerin in vascular dysfunction in diabetes‐ and obesity‐associated diseases.Support or Funding InformationFAPESP 2012/13144‐8; 2015/01630‐3.
Unpleasantness and Negative Emotions Related to Dyspnea on Exertion in Obese Women
Authors: Marines‐Price Rubria , Vipa Bernhardt , Bhammar Dharini , Stickford Jonathon , Bassett J. Todd , Roman Maria C , Babb Tony G 
Published: November 2023

IntroductionDyspnea on exertion (DOE) is a common complaint in otherwise healthy obese women, which may influence and prevent them from engaging in physical activity. DOE is composed of at least two dimensions: sensory (i.e., intensity) and affective (i.e., emotional response). We examined whether subjective ratings of breathlessness (RPB) during exercise were associated with unpleasantness and negative emotions, including depression, anxiety, frustration, anger, and fear.MethodsOtherwise healthy, obese women underwent hydrostatic weighing and a 6 minute constant‐load cycle test at 60 W. RPB was recorded during the last minute of the cycling test as a measure of the sensory dimension of dyspnea. Visual analog scales were used to assess unpleasantness and negative emotions as a measure of the affective dimension of dyspnea immediately after the exercise.ResultsSeventy‐four women (34 ± 7 years, 36 ± 4 kg/m2, 46 ± 5 % body fat) participated. The strongest correlations were between RPB and unpleasantness (r = 0.61, p <0.001) and RPB and anxiety (r = 0.50, p < 0.001).ConclusionsUnpleasantness and anxiety were associated with RPB, indicating that some obese women not only perceive a heightened sense of breathlessness intensity, but also experience negative emotions, specifically unpleasantness and anxiety, related to the breathlessness. Thus, it is important for healthcare providers to assess not only intensity ratings, but also the associated negative emotions, that may accompany DOE (i.e., affective dimension). Future research should focus on interventions that can help alleviate both sensory and affective symptoms of related to DOE.Support or Funding InformationNational Institutes of Health Grant HL096782, King Charitable Foundation Trust, Texas Health Presbyterian Hospital Dallas
Effect of Plant Sources of Omega‐3 PUFA on Mood Status in Healthy Subjects: A Cross Over Feeding Trial
Authors: Young Wajeeha Mazhar 
Published: November 2023

Study ObjectiveThe high prevalence of mood disturbance and inadequate efficacy of current antidepressants necessitates the search for more effective treatments. Omega‐3 PUFA may provide one such option. The aim of this paper is to test if changes in the ratio of dietary n6:n3 FA, and/or use of EPA/DHA algae supplement, is associated with changes in mood disturbance in healthy adults.MethodsThis was a tightly controlled, factorial design, randomized feeding trial (n=24) evaluating the effects of dietary intake of two n‐6:n‐3 PUFA ratios on mood states. The n‐6: n‐3 ratios of 10:1 and 2:1 in experimental diets were provided from plant sources. Subjects were randomized into 8‐week, cross‐over diet sequences where each subject consumed three of four dietary treatments: the two diets, with/without algae supplements. Subjects completed the Depression Anxiety Stress Scale (DASS) and the Profile of Mood States (POMS) questionnaires at the end of each 8‐week study period.ResultsSubject distress scores were within normal range throughout the duration of the study period. There was no statistically significant difference in DASS or POMS scores between the four diets. However there was a consistent tendency towards increased distress with the addition of algae supplement with summation of mood disturbance reaching significance. Change in dietary n‐6:n‐3 FA ratio did not play a role in mood disturbance. However, intake of EPA/DHA algae supplement resulted in increased overall mood disturbance as measured by DASS and POMS.ConclusionsThese findings suggest that EPA/DHA supplements may not be advisable for healthy adults.Support or Funding InformationFunded by the Center for Health and Nutrition Research, University of California, Davis
Food Insecurity's Association with Gestational Weight Gain Varies by Pre‐pregnancy Weight and Parity
Authors: Metallinos‐Katsaras Elizabeth , Siu Elizabeth , Colchamiro Rachel 
Published: November 2023

Food insecurity and excessive gestational weight gain (GWG) have both been associated with increased risk for obesity among women. This study examined the predictive value of household food security status (FSS), assessed prenatally, for gestational weight gain among low‐income women during their first and second pregnancies. Mothers enrolled in Massachusetts WIC (2001–2009) with two consecutive (linked) pregnancies were included. Only those with singleton, full term, live, adequate‐birth‐weight infants and with complete data on covariates and HH food security assessed at the first prenatal visit of the first (n=12,215) and second pregnancies (n=10,844) were included. The sample was diverse (55% nonwhite) with a mean age of 22.3 years (SD=5.0) and a mean gestational weight gain of 36.3 lbs (SD=15.1); 30.1% reported HH food insecurity at their first prenatal visit, with 7.7% reporting very low food security. Weight status prior to the first pregnancy was as follows: 6.7% underweight, 57.1% normal weight, 21.8% overweight, and 14.4% obese. General linear model regression examined the association between household FSS in early pregnancy and GWG (pounds) for each pregnancy, controlling for race/ethnicity, age, education, household size, timing of WIC entry, and acculturation. Additionally, inter‐pregnancy interval was included as a covariate for the second pregnancy's GWG. Analyses were stratified by pre‐pregnancy weight status because of a significant interaction between weight status and FSS (p<.05). First pregnancy's prenatal FSS, was associated with GWG among those who were overweight (BMI > 25 and < 30) but not among underweight, normal weight or obese mothers; overweight mothers with very low food security had higher GWG during their first pregnancy (adjusted mean=38.2 lbs.) than those who were food secure (34.1 lbs., p<.001) or had low food security (34.9 lbs., p < .01). Second pregnancy's prenatal FSS was associated with GWG among those who were obese (BMI>30); those who reported any food insecurity had a significantly higher weight gain than those who were food secure (29.8 vs. 28.2 pounds, p<.05). No association between second pregnancy's FSS and GWG was found among women who were underweight, normal weight or overweight prior to their second pregnancy. Food insecurity in early pregnancy is related to GWG differently, depending on pre‐pregnancy weight status and parity.Support or Funding InformationSimmons College President's Fund
Initiation of Smell in Congenital Smell Loss
Authors: Henkin Robert I , Abdelmeguid Mona , Knoppel Alexandra B 
Published: November 2023

There are about 500,000 patients in the United States with congenital loss of smell, patients born without any sense of smell. The largest group of these patients have no gross brain abnormalities as determined by brain imaging, no anatomical abnormalities of the peripheral olfactory system as determined by nasal endoscopy, no other known congenital defects and no family history of smell loss. Congenital biochemical abnormalities of their olfactory system comprise several biochemical changes from normals: inhibition of secretion of nasal growth factors cAMP, cGMP and sonic hedgehog (Shh) which normally stimulate stem cells in the olfactory epithelium to initiate growth of olfactory receptors and activation of “death factors” TNFα and TRAIL which pathologically inhibit growth of olfactory receptors. We treated 19 of these patients, aged 6–61 years, with the phosphodiesterase inhibitor theophylline, 200–800mg daily for 2–36 months with smell function and nasal mucus growth and “death” factors measured at intervals of 2–10 months. Results indicated that smell function was initiated in 12 of these patients (63%) and quantified by both subjective return of smell function and by olfactometry. Significant increases in nasal mucus cAMP, cGMP and Shh and inhibition of nasal mucus TNFα and TRAIL occurred with theophylline treatment in these patients. Initiation of smell function occurred after theophylline treatment for 2–18 months and persisted as long as therapy was continued. This is the first report of initiation of smell function in patients with congenital smell loss. This initiation was associated with correction of congenital biochemical abnormalities in their nasal mucus growth and “death” factors.Support or Funding InformationNone
A Randomized, Controlled, Parallel Study to Assess the Effects of Soy Protein on Body Composition and General Health Parameters in Healthy Children
Authors: Braun Michelle , Cook Chad , Mukherjea Ratna , Liska DeAnn 
Published: November 2023

It is currently unknown whether a moderate increase in daily protein intake from lean, high quality sources will affect body composition in young growing children; however, research has demonstrated a role for higher protein diets supporting healthy body composition in adults. The aim of this randomized, controlled, parallel clinical study was to assess the effects of daily consumption of soy protein foods on body composition, general health status, sleep habits, mood, and dietary intake outcomes in generally healthy children.Subjects were male and female children, 8–11 years of age, with a body mass index (BMI)‐for‐age within the 75th–95th percentile and habitual consumers of breakfast and snacks. Subjects were randomly assigned into one of two groups: 1) a Usual Protein (UP) group counseled to follow the 2010 Dietary Guidelines for Americans, in which 14% daily energy intake was from mixed protein sources, or 2) a Supplemental Protein (SP) group counseled similarly, but also provided lean protein sources to incorporate into their daily diet to reach 20% daily energy intake from protein. Both groups followed their assigned intervention for 12 weeks. The SP group incorporated study foods that were matched so each food item delivered 15 g of protein from soy. Multiple study product choices were provided, including vegetarian snack sticks, meal patties and 2 flavors of protein bars for inclusion at breakfast and a snack, leading to additional daily soy protein intake of 30g per day, as part of the counseled diet. Dual Energy X‐ray Absorptiometry (DXA) was used to determine changes in body composition from baseline to end of intervention.Subjects were well matched for baseline anthropometric characteristics (BMI‐for‐age 86.8 ± 0.9 percentile), age (9.5 ± 0.2 y), and sex (24 males, 23 females), with no observed significant differences between the two groups (n=24 in UP, n=21 in SP). Results from 3‐day diet records revealed no differences in energy intake between groups, but the SP group had significantly higher protein intake at the end of the 12 week intervention (UP 69.5±5.3g, SP 93.7±3.2g, p<.001). Quality of life assessments revealed similar responses between groups. Both groups increased fat free mass from baseline, with no significant differences observed between groups.This study demonstrates lean protein such as soy can be incorporated into a diet consistent with Dietary Guidelines to increase protein intake in children. Given that many groups are recommending increased energy from protein, this approach is an option to help aid in prevention or manage obesity.Support or Funding InformationFunding provided by DuPont Nutrition & Health