bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of obesity in Ossabaw pigs fed diets high in saturated and n‐3 fatty acids
Authors: Faris Richard , Braucher Douglas , Walker‐Daniels Jennifer , Spurlock Michael 
Published: June 2021

Western diets high in saturated fat have been implicated in the increasing rate of obesity within the U.S. Saturated fatty acids are of considerable interest because of their interaction with toll like receptors in adipose tissue and contribution to chronic low‐grade inflammation. In contrast, n‐3 fatty acids are generally viewed as being anti‐inflammatory. To determine the impact of supplement a western diet with n‐3 fatty acids, 26 Ossabaw pigs with an initial body weight of 47.4 kg were fed 3 diets: a restricted low fat control diet (LFC, 2750 kcal/kg), a high fat palm oil diet (HFP, 4000 kcal/kg), and a high fat palm oil with n‐3 supplement diet (HFPn3, 4000 kcal/kg). At 8 weeks there was no difference in body weight between the HFP and HFPn3 diets (77.6 vs. 79.4 kg), nor was there a difference in caloric intake. Fasted serum glucose and insulin concentrations were increased at 8 weeks in pigs feed both the HFP and HFPn3 relative to the LFC group. Additionally, fasted serum cholesterol was increased at 8 weeks by the high fat diets, but there was no difference between HFP and HFPn3 groups. Collectively, these data indicate that the n‐3 supplementation alone for 8 weeks in insufficient to attenuate obesity or the onset of insulin resistance cause by diets high in saturated fat. This project was supported by National Research Initiative Grant 2008–35200–04466 from the USDA National Institute for Food and Agriculture.Grant Funding Source: USDA
High dietary calcium does not mediate the effects of dairy to reduce adiposity and improve glucose tolerance in high fat fed mice
Authors: Thomas Anthony Pelico , Dunn Tamara N. , Drayton Josephine B. , Adams Sean H. 
Published: June 2021

Epidemiological studies and research in animal models support an inverse relationship between dietary Ca and dairy food consumption with adiposity. Proposed mechanisms of adiposity reduction by dairy include decreased digestibility of fats due to formation of indigestible Ca soaps and dietary Ca suppression of calcitriol that alters energy metabolism and thermogenesis. Bioactive components from dairy protein are thought to have additional synergistic effects. We compared the effects of a high Ca (HC) diet vs. HC with nonfat dry milk (NFDM) on obesity phenotypes, including adipose tissue inflammation. Adult male C57BL/6J mice fed an obesigenic, pro‐inflammatory high fat diet (45% kcal; HF) were assigned (n=30/group) to one of three macronutrient‐matched HF diets for 12 wks: control (0.5% Ca; CON), HC (1.5% Ca), or HC with NFDM. Surprisingly, body weight and fat were increased ~18% and ~19% in HC mice vs. CON (P<0.001); these parameters decreased ~13% and ~43% in NFDM mice (P<0.001). Feed efficiency was significantly increased ~10% in HC mice and reduced ~33% in NFDM mice vs. CON. NFDM mice had improved glucose tolerance compared to both CON (P<0.01) and HC mice (P<0.001). Markers of adipose inflammation are currently being analyzed. We conclude that anti‐obesity effects of dairy foods are not mediated by increased dietary Ca in high fat fed mice.Grant Funding Source: National Dairy Council and ARS Project 5306–51530–016–00D
Effect of dietary restriction and n‐3PUFA supplementation on insulin resistance in obese adults
Authors: Tapsell Linda Clare , Batterham Marijka Jane , Charlton Karen Elizabeth 
Published: June 2021

The type and amount of dietary fat, and in particular n‐3 PUFA, may influence insulin action. The aim of this study was to examine the effects on HOMA indices from increased n‐3 PUFA intakes at 3 and 6 months in a registered 12 month weight loss trial [ACTRN12608000425392]. The blinded RCT with 30 males and 88 females (aged 45+9.95yr; BMI 31.34+3.49kgm−2) compared a control diet (2MJ deficit, 30%fat + placebo) with two intervention groups (2MJ deficit, 30% fat emphasizing fish with placebo or supplement of 420mg EPA+ 210mg DHA). Differences between groups were assessed using repeated measures analysis of variance, where data was available at 0,3,6mo (n=73). A significant time effect was found for decreased HOMA‐R (inverse of %S) (P=0.001), with post hoc analysis showing a significant difference between 0–3mo (P=0.006) and 0–6mo (P=0.002). Values for the control group were higher than for the intervention groups but the effect was not significant at 3–6mo (P=1.000). No effect was seen for HOMA(%β) (N=72). Energy restriction appears to decrease insulin resistance in overweight adults in the first 3 mo, and there may be added benefits with food or supplemental n‐3 PUFA dietary enrichment.Source of research support: Australian National Health and Medical Research Council Project Grant #514631 Tapsell, Batterham, Charlton.
Beta‐hydroxy‐beta‐methylbutyrate (HMB) Decreases Body Fat in Middle Aged and Old Rats
Authors: Wilson Jacob Malachi , Lee Sang‐rok , Henning Paul , Ugrinowitsch Carlos , Grant Samuel , Park Young‐min , Masad Ihssan , Leonard Ken Paul , Zourdos Michael , Bakhshalian Neema , Panton Lynn , Kim Jeong‐su 
Published: June 2021

Adipose and muscle mass increase in Fisher 344 (F344) rats through midlife and decline thereafter. HMB increases fat oxidation and activates anabolic pathways in myotubes. We determined the effect of HMB on adiposity and muscle wet weights in F344 rats. Twelve young (44 wks), 6 middle aged (60 wks), 10 old (86 wks), and 5 very old (102 wks) male F344 rats’ body compositions were assessed using dual X‐ray absorptiometry (DXA) pre/post‐treatment. After DXA, 6 young, 6 middle aged, 5 old and very old rats were sacrificed for pre and post control muscle wet weights. Remaining young and old rats were given HMB (0.46 g/kg/d) for 16 wks. There was a group effect for body mass (BM) increasing (+23%) in the control, but not in the HMB group from 44–60 wks, while it maintained in the control, and declined (−20%) in the HMB group from 86–102 wks. There were declines in gastrocnemius, plantaris, and soleus weights normalized to BM from 60–102 wks. While HMB had no effects on the gastrocnemius, there were decreases in control planaris (−21%) and soleus (−15%) muscles, which maintained and increased (+12%), respectively, in the HMB group from 44–60 wks. Fat mass (g) increased in the middle aged control (+49%) but not in the HMB group. Fat mass declined (−56%) in the old HMB but not in the control. Our findings suggest HMB may produce a leaner phenotype in middle aged and older individuals. Future research is needed to elucidate the underlying mechanisms.Grant Funding Source: College of Human Sciences Internal Grant
Life expectancy of beagles
Authors: Yu Shiguang 
Published: June 2021

Life expectancy of beagles was calculated from 303 beagles (162 female and 141 male) with known birth and death dates. Most of the dogs were either spayed or castrated during the first year of their life. Both natural death and euthanasia due to terminal illness were considered as a death event. These beagles received regular veterinary medical care during their life.Gender had no effect on median survival of beagles (male = 12.82 years; female = 12.87 years; p = 0.610). Therefore, combined data of both male and female beagles were used for the calculation of the life expectancy. The age specific median residual lifetime (age in years/median residual lifetime in years) was 0.5/12.8, 1.5/12.1, 2.5/11.1, 3.5/10.1, 4.5/9.1, 5.5/8.2, 6.5/7.2, 7.5/6.3, 8.5/5.4, 9.5/4.5, 10.5/3.7, 11.5/2.8, 12.5/2.1, 13.5/1.6, 14.5/1.2, and 15.5/0.6. Mortality increased dramatically in beagles after 9 years of age (95% CI: 8.7, 10.0 years). The results of this study suggest that earlier diagnostic or therapeutic intervention is warranted in beagles beginning at 9 years of age. This study was supported by Hill's Pet Nutrition, Inc.
Flaxseed consumption lowers insulin, C‐reactive protein and fructosamine in adults with pre‐diabetes
Authors: Hutchins Andrea M , Brown Blakely D , Domitrovich Stephanie 
Published: June 2021

The purpose of this study was to determine whether eating modest amounts of flaxseed daily would improve glucose control, insulin levels, and markers of inflammation in overweight or obese men and postmenopausal women with pre‐diabetes. During 3 treatment periods (each 12 weeks long), 25 participants consumed 2 tablespoons (tbsp) ground flaxseed daily, 4 tbsp ground flaxseed daily or no flaxseed (control). Participants completed a 12‐hour fasted blood draw and a first void (morning) urine collection before and after each intervention.Consuming 2 tbsp flaxseed significantly lowered insulin values compared to 4 tbsp flaxseed intervention or control. When participants consumed 4 tbsp of flaxseed, C‐reactive protein values significantly decreased compared to consuming 2 tbsp flaxseed or control. Participants with glucose values between 110–125 mg/dL on study entry had significantly lower fructosamine values consuming either 2 or 4 tbsp flaxseed compared to control.In conclusion, consuming 4 tbsp flaxseed lowers inflammation in adults with pre‐diabetes and improves glycemic control in some individuals. Consuming 2 tbsp flaxseed lowers insulin values in adults with pre‐diabetes, indicating a decrease in insulin resistance. Consequently, daily flaxseed consumption can help adults with pre‐diabetes improve glucose control.This study was funded by the American Diabetes Association, grant 7‐06‐RA‐61.
Effect of food form on postprandial plasma amino acid profiles in older adults
Authors: Conley Travis B , Apolzan John W , Leidy Heather J , Campbell Wayne W 
Published: June 2021

Purpose and MethodsTo assess the effect of food form on the postprandial (PP) plasma amino acid (AA) profile, 10 healthy older adults (5 men and 5 women, age 72 ± 2 y, BMI 26.0 ± 0.9 kg/m2) consumed energy and macronutrient matched test meals (~25% of subject's daily energy need; ~54% CHO, 21% Pro; 25% Fat) in beverage and solid form on separate days. Blood samples were taken during fasting (baseline) and throughout the 4‐hour PP period and plasma AA profiles (pmol/uL) were assessed using high performance liquid chromatography.ResultsThe consumption of each test meal led to an increase in total, branched chain (BCAA), essential (EAA), and non‐essential (NEAA) AA contents over the 4‐h period (time effect; p<0.05). The beverage stimulated a greater increase in total, EAA and NEAA contents, but not BAA content, vs. the solid (effect of food form; p<0.05). The beverage elicited higher plasma AA levels starting at 15 min PP which was maintained for the rest of the 4‐h period. The beverage also resulted in a greater total plasma AA 4‐h area under the curve (p<0.05).ConclusionOlder adults can achieve higher plasma amino acid contents when a protein‐containing food is ingested in beverage form. Future research to explore the utility of this higher amino acid substrate availability on anabolic processes is needed.Support: NIH R01 AG021911, The Solae Company®, Purdue Ingest Behav Res Ctr and Bilsland Fellowship
Dietary protein quality influences the pattern of natural isotopic composition of nitrogen in rats
Authors: Poupin Nathalie , Fouillet Hélène , Mariotti François , Tomé Daniel , Huneau Jean‐François , Bos Cécile 
Published: June 2021

The natural 15N enrichment (δ15N) in some specific tissues (blood, hair) has been shown to vary with diet quality. In this work, we investigated the influence of two dietary protein sources of different quality (milk and soy) on the δ15N values in various tissues. Male Wistar rats (n=18) were fed for 3 weeks experimental diets differing only in their protein source (soy or milk). δ15N values were determined in both protein and non‐protein fractions of blood and peripheral (muscle, kidney, skin) and splanchnic (liver, intestine) organs. Results were expressed as diet‐tissue discrimination (Δ15N = δ15Ntissue − δ15Ndiet). Regardless of the diet, the protein fraction of tissues was always enriched in 15N relative to the non‐protein fraction and relative to the diets (Δ15N>0). Δ15N of protein fractions differed among tissues and were also influenced by the protein source. They were indeed higher in rats fed with soy (vs. milk) diet, in all tissues but the intestine (see Fig.). We conclude that Δ15N is lower when dietary protein quality is higher. Furthermore, the amplitude of Δ15N differences between diets varied among tissues (being for instance 3‐fold higher in skin than in liver), indicating that the nature of the dietary protein source differentially impacts the metabolism of splanchnic and peripheral tissues. We propose that Δ15N is a sensitive marker of protein biological value and regional protein metabolism.image
Experimental hyperthyroidism treated with acupuncture ‐ metabolomic evaluation of Wistar rats' livers
Authors: Cabral António Jorge Varela , Machado Vanessa Isabel , Nolasco Varão , Tavares Ludgero , Farinha Rodrigo , Carvalho Rui , Cabrita António 
Published: June 2021

Hyperthyroidism can be defined as the consequence of production and excessive action of the thyroid hormones. Acupuncture as been proven effective in the treatment of some pathologies, with minimum side effects.Twenty‐one male Wistar rats were divided into 3 groups: group I – control with no manipulation (Ctrl); group II – received levothyroxine (HT); group III ‐ received levothyroxine and acupuncture (HT+AC). Liver samples were snap frozen in liquid nitrogen and later analyzed by high rotation magic angle NMR spectroscopy (HRMAS) in a in a 14.1 Tesla Varian spectrometer. HRMAS spectral analysis followed by principal component statistical analysis demonstrated that lipids were significantly reduced in the HT group and increased in the HT+AC, the same happening with the aminoacids aspartate and glutamate. Glucose, as well as glycogen were significantly increased in both HT and HT+AC groups.The results suggest that HT reduces hepatic lipid contents, either by increased mobilization or reduced de novo lipogenesis, and that such reduction is reversed by AC treatment. The increase in glucose content is compatible with either an increase in glycogen breakdown or an increase in gluconeogenesis. Our results show an increase in glycogen content in both HT and HT+AC groups thus supporting the later. Accurate evaluation of lipogenesis and glucose turnover is currently underway using the 2H2O method.
Paracrine induction of fibroblasts by breast cancer cells and their effect on endothelial cell migration
Authors: Rocha Ana Sofia , Pirraco Ana , Soares Raquel 
Published: June 2021

The aim of this work was to demonstrate the relevance of the interplay between fibroblasts and breast cancer cells in angiogenesis and metastasis development.Fibroblasts were treated with conditioned media from the breast cancer cells lines (MCF7 and MDA‐MB‐231). The cultures were evaluated for apoptosis by TUNEL assay, proliferation by BrDU incorporation assay and migration by double‐chamber assay. To examine whether tumor‐induced fibroblasts were able to stimulate endothelium invasion, HUVECs were cultured in a double‐chamber and subjected to conditioned media‐treated fibroblasts.Apoptosis and proliferation were not affected by conditioned media‐treated fibroblasts as compared to non‐treated cells. However, these cells present higher migration ability. Migration of HUVECs was significantly induced by fibroblasts whenever these were stimulated by breast cancer conditioned media.Our findings suggest that fibroblast migration is enhanced by breast cancer‐secreted growth factors. In addition, cancer‐induced fibroblasts strongly stimulate endothelial cells migration. These data was corroborated by matrigel plug assay. Taken together, these results reveal the importance of fibroblasts and their primary role in tumor angiogenesis.
Anti‐inflammatory effect of bee venom in amyotrophic lateral sclerosis model
Authors: Yang Eun Jin , Jiang Jing Hua , Lee Sang Min , Lee Myeong Soo , Choi Sun Mi 
Published: June 2021

Amyotrophic lateral sclerosis (ALS), paralyzing disorder is characterized by the progressive degeneration and death of motor neurons occurring both as a sporadic and a familial disease. Mutant SOD1(mtSOD1) induces vulnerability of motor neurons through protein misfolding, mitochondrial dysfunction, oxidative damage, cytoskeletal abnormalities and defective axonal transport, excitotoxicity, inadequate growth factor signaling, and neuro inflammation.Bee venom (BV) known as an Oriental medicine has been reported the evidence in the literature indicated that BV exerts anti‐inflammatory and anti‐nociceptive effects on inflammatory reactions in arthritis and other inflammatory diseases.The purpose of the present study is to determine whether acupuncture with BV is able to suppress the motor neuron loss and microglial cell action in hG93ASOD1 mouse commonly used model for inherited ALS. BV was treated at the ‘ZuSanLi’ (ST36) acupuncture point in hSODG93A animal model. BV treated animals showed the decrease of micro cell activity and the expression level of phospho‐p38MAPK in spinal cord and brain stem in mutant hSOD1 transgenic mice. Interestingly, BV acupuncture in symptomatic ALS animals improved motor activity and extended survival compared to the control group. Our research suggests a potential functional link between BV and anti‐neuroinflammation in ALS animal model.the neurotoxicity of mutSOD1 is nUp to date, no data exist about a link among neuroinflammation, mutSOD1 association in mitochondria and oxidative damage.
Roll of Toll‐like Receptor 9 in Mouse Lung Inflammation in Response to Chicken Barn Air
Authors: Schneberger David , Aulakh Gurpreet , Channabasappa Shankaramurthy , Caldwell Sarah , Singh Baljit 
Published: June 2021

Exposure to barn air is an occupational hazard that results in lung dysfunction in barn workers. These respiratory symptoms are typically associated with endotoxin, but within these environments gram negative bacteria may constitute only a small portion of the species and quantity of microorganisms. In contrast, un‐methylated DNA by can be found in all bacteria, most viruses and, and mould. Therefore, we investigated the role of TLR9, which binds to un‐methylated DNA, in barn‐air induced lung inflammation.First we used immunohistology, immuno‐electron microscopy and in situ hybridization to show expression of TLR9 on bronchial epithelium, alveolar septal cells, and alveolar macrophage of mouse and human lungs. Using a TLR9‐deficient mouse model, these animals were exposed to barn air for 8 hours/day for 1, 5, or 20 days. Examination of bronchiolar lavage and serum against a panel of six common cytokines (IL‐1β, IL‐6, IL‐10, IL‐12, TNF‐α, and IFN‐γ) showed no significant differences after a single day exposure. While TNF‐α (p=0.06) levels in TLR9‐deficient mice were reduced in blood and lavage fluids after 5 and somewhat reduced at 20 days of exposure (p=0.14), IFN‐γ at 5 days(p=0.06) remained reduced after 20 days (p=0.05). Taken together, our data shows expression of TLR9 in mouse and human lungs and that TLR9 may partially contributes to inflammation induced following exposure to chicken barn air.Grant Funding Source: NSERC Discovery Grant
Receptor signaling and behavioral properties of EFF0311, a longer‐acting selective full D1 agonist as a potential treatment for Parkinson's disease
Authors: Murthy Vishakantha , Lieu Christopher A , Gowdahalli Krishnegowda , Blake Daniel , Amin Shantu , Subramanian Thyagarajan , Mailman Richard B 
Published: June 2021

D1 dopamine full agonists like dihydrexidine (DHX) were previously used to show that D1, but not D2, agonists could match the efficacy of levodopa in the primate MPTP Parkinson's disease (PD) model and in humans with PD. Short duration of action, toxicity, and/or limited bioavailability have prevented a D1 agonist from being approved for clinical use, with only DHX (very short acting) available for limited investigator‐initiated clinical studies. We now report the properties of EFF0311, a DHX analog with greater D1 selectivity and nanomolar affinity for D1 and D5 receptors. EFF0311 had 100% intrinsic activity in stimulating adenylate cyclase via D1 receptors in expressed systems or brain. EFF0311 (relative to quinpirole) was far less potent at D2L‐mediated stimulation of arachidonic acid release than in inhibition of forskolin‐stimulated adenylate cyclase, consistent with functionally selective actions at D2L receptors. In the unilateral 6‐OHDA rat model of PD, EFF0311 effects lasted 3–5 times longer than DHX. These behavioral effects were completely blocked by a D1 antagonist, but not decreased by a D2 antagonist. The properties of EFF0311 (D1 full agonism, longer duration of action, atypical D2 actions) suggest it may be an ideal PD drug candidate.Grant support: MH082441, MH040537, PA Keystone Innovation Grant (RBM), NS042402 and PA Tobacco settlement fund (TS). RBM has a potential CoI.
The role of D‐serine and other D‐amino acids in a mouse model of amyotrophic lateral sclerosis (ALS)
Authors: Thompson Misty , Reed Ron , Bennett Patrick , Crow John 
Published: June 2021

ALS is a fatal disease characterized by selective death of motor neurons (MNs) in the spinal cord. Mutations to Cu, Zn superoxide dismutase (SOD1) have long been known to be a cause of ALS, but the molecular mechanism remains unknown. In the presence of mSOD1, MNs are subjected to increased levels of glutamate excitoxicity via the NMDA receptor, which may be related to increased production of the co‐agonist D‐serine (D‐Ser) from activated glial cells.As proof of concept, we examined the effects of D‐ser treatment on age of onset, survival, and MN viability in mSOD1 ALS mice. D‐ser treatment resulted in earlier symptom onset by 14.6 ± 0.5 days versus untreated littermates. Paradoxically, D‐ser treatment significantly extended the survival interval (time from onset to sacrifice) by approximately 20 days. The bi‐phasic response to D‐ser may be related to induction of enzymatic D‐ser degradation by D‐amino acid oxidase (DAO). Studies are ongoing to examine spinal cord levels of DAO and serine racemase (produces D‐ser in vivo), both in terms of protein and enzyme activity, levels of D‐amino acids, and overall changes in the proteome (via quantitative 2D‐DIGE proteomics analysis) as a function of disease progression and D‐ser treatment. Our results suggest that the relative concentrations of D‐ser and L‐ser over time may be more important than the absolute concentration of D‐ser alone. Funded by NIH R01 2R01NS040819‐12 (JPC).
L‐pGlu‐(1‐Benzyl)‐L‐His‐L‐ProNH2: a Newer Thyrotropin‐Releasing Hormone Analog with anticonvulsive and neuroprotective properties
Authors: Rajput Satyendra Kumar , Singh Jitendra , Meena Chhuttan , Jain Rahul , Pant Aditya , Sharma Shyam 
Published: June 2021

ObjectiveTo study the role of L‐pGlu‐(1‐benzyl)‐L‐His‐L‐ProNH2 (NP‐355) in models of seizures and cellular injury.MethodsSeizures were induced in mice by pentylenetetrazole (PTZ; 65mg/kg, ip), picrotoxin (PTX; 3.2 mg/kg, sc) and kainic acid (KA; 35mg/kg, ip). Cerebral blood flow (CBF) was measured with laser Doppler in anaesthetized mice. Sodium current was recorded in cultured neonatal rat dorsal root ganglion neurons (DRG) using whole cell patch clamp technique. Glutamate, H2O2 and oxygen glucose deprivation (OGD)‐induced cell injury was studied in PC‐12 cells using MTT assay.ResultsNP‐355 pretreatment showed significant protection in PTZ‐, PTX‐ and KA‐ induced seizures, increased the CBF and its exposure produced depression of sodium current in DRG neurons. In vitro, NP‐355 showed protection from glutamate (15mM) ‐ and H2O2 (0.3mM) ‐ induced cellular injury in a time‐ and concentration‐ dependent manner. The maximal protection was observed after 24 hr of incubation and at 10 μM concentration. The cell viability was increased from 36% to 88% and from 54% to 90% after glutamate and H2O2 treatment in presence of NP‐355. Similarly, a significant difference in cell viability was observed in OGD group with (84%) and without (66 %) treatment. NP‐355 didn't show any abnormal effect on CNS.ConclusionNP‐355 is a safe anticonvulsant and neuroprotective agent, also has protective potential against ischemia.