bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased circulating trimethylamine N‐oxide, a gut‐flora‐dependent metabolite of choline and betaine in nonalcoholic fatty liver disease is associated with high serum bile acids
Authors: Zhu Hui‐lian , Tan Xu‐ying , Liu Yan , Chen Xiao‐ling 
Published: November 2023

ObjectiveTrimethylamine‐N‐oxide (TMAO) is a gut‐flora‐dependent metabolite of choline and betaine and could dysregulate the bile acids (BAs) metabolism. Many study suggested that elevated circulating TMAO contributes to the risk of cardiovascular diseases, but little is known for non‐alcoholic fatty liver disease (NAFLD). Evidence has linked that elevated circulating bile acids (BAs) level was detrimental to the fatty liver. The pathological mechanisms of TMAO on NAFLD via bile acids are not fully understood. Herein, we examined the association of circulating TMAO, BAs, choline and betaine with the presence and severity of NAFLD in Chinese adults. We also explored correlation of TMAO and BAs and the mRNA expression of bile acid metabolic enzyme.MethodsWe performed a hospital‐based case‐control study. We recruited 60 biopsy‐proven NAFLD cases and 35 controls (18–60 years) and determined serum concentrations of TMAO, BAs, choline and betaine by high‐performance liquid chromatography with online electrospray ionization tandem mass spectrometry (HPLC‐MS/MS). The expression of hepatic bile acids synthesis genes cholesterol 7α‐hydroxylase (CYP7A1) and sterol 27‐hydroxylase (CYP27A1), bile acids transporters genes sodium taurocholate cotransporting polypeptide (NTCP) and bile salt export pump (BSEP) were examined by reverse transcriptase‐polymerase chain reaction (RT‐PCR).ResultsIn this case control study, serum TMAO increased by 92%, total BAs by 37%, choline by 66.3%, unconjugated BAs by 81%, glycine‐conjugated bile acids (G‐BAs) by 57%, and the ration of betaine /choline decreased by 30.1% in NAFLD patients compared with normal ones and showed significant differences (all P<0.05). Multivariate analyses showed adverse associations of ln‐transformed serum levels of TMAO, total BAs, unconjugated BAs and, G‐BAs and favorable association of betaine/choline ratio with the scores of steatosis and total NAFLD activity (NAS) (all P‐trend <0.05). Circulating TMAO was observed a positively correlated with serum concentration of unconjugated BAs (r=0.306, P=0.022) and G‐BAs (r=0.248, P=0.014). Gene expression of hepatic CYP7A1 were significantly increased (P=0.003) in NAFLD and showed dose‐dependent positive association with serum TMAO (P trend=0.038).ConclusionIn this case‐control study, our findings suggested adverse associations between the circulating TMAO, choline and BAs level and the presence and severity of NAFLD in Chinese adults. We also found a favorable betaine/choline ration ‐NAFLD relationship. The mechanism of TMAO on NAFLD might be explained by its promoting the expression of bile acid metabolic enzyme of CYP7A1.
Changes in dietary profiles, markers of cardiometabolic health and cognitive function following 12 weeks of peanut consumption
Authors: Coates Alison , Barbour Jayne , Buckley Jonathan , Bryan Janet , Howe Peter 
Published: November 2023

BackgroundImpairments in cardiometabolic health and cognitive function increase with ageing; key dietary macronutrients and micronutrients may counteract these effects. Peanuts contain protein, unsaturated fatty acids, fibre, vitamins and bioactive compounds such as polyphenols that have the potential to improve cardiovascular and cognitive health.AimTo investigate the effect of 12 weeks of daily consumption of Hi‐Oleic Australian peanuts compared with a nut free diet on cardiometabolic risk markers and cognitive function.MethodsSixty‐one healthy participants (65±7y, BMI 31±4 kg/m2) consumed peanuts (56g/d for 32F; 84g/d for 29M) or no nuts (control) in addition to their habitual diet for 12 weeks each in a randomised crossover design. Diet profiles during each phase were captured using 4‐day weighed food diaries. At baseline and the end of each 12‐week period the following were measured: fasting blood lipids, glucose and insulin, blood pressure, arterial compliance, body composition (DEXA) and inflammation, and cognitive tests were conducted to assess memory, processing speed and executive function.ResultsDuring the peanut phase compared with the control phase total energy increased by 12% due to higher intakes of protein (12%) and total fat (30%, predominately MUFA). Intakes of fibre (15%), vitamin E (66%), folate (29%) and magnesium (22%) were also increased. Higher MUFA was associated with reductions in fat mass (r=−0.26, p=0.04) and insulin (r=−0.28, p=0.03); higher vitamin E was associated with better large artery elasticity (r=0.27, p=0.04) and higher folate was associated with better memory recall (r=0.35, p=0.007).ConclusionAdding Hi‐Oleic peanuts to a nut‐free habitual diet increased consumption of key macronutrients and micronutrients which were associated with improved cardiometabolic risk and memory. Over a longer‐term, peanuts may assist in limiting cardiometabolic risk and cognitive impairments associated with ageing.Support or Funding InformationAustralian Linkage Grant in partnership with the Peanut Company of Australia
Knockdown Glucose‐6‐Phosphate Dehydrogenase promotes EMT through downregulation of E‐cadherin by miR‐200b inhibition in A549 cells
Authors: Wu Yi‐Hsuan , Lee Ying‐Hsuan , Chiu Daniel Tsun‐Yee 
Published: November 2023

Glucose‐6‐phosphate dehydrogenase (G6PD) is a house keeping enzyme and is a rate limiting enzyme in the pentose phosphate shunt to regenerate NADPH. Tumorigenesis is often accompanied by increased glycolysis and G6PD activity. However, treatment with TGF‐β, commonly used to induce epithelial‐mesenchymal transition (EMT), inhibits G6PD expression in tumor cells (Accession No. GDS3710). Therefore, the roles of G6PD on tumorigenesis, particularly on EMT need to be clearly defined. In the present study, whether G6PD modulate EMT process in cancer cells through miRNA was evaluated. G6PD‐knockdown cells showed a more mesenchymal‐like morphology. The changes in morphology were accompanied by increase of migration of these cells. Suppression of epithelial markers, E‐cadherin, and increase of N‐cadherin were observed in G6PD‐knockdown cells. The anticancer miRNAs, especially miR‐200b, a regulator of E‐cadherin expression, was downregulated in G6PD‐knockdown cells as documented by miRNA profiling. Ectopic expression of G6PD in G6PD‐knockdown cells upregulates the expression of miR‐200b and E‐cadherin. Taken together, these results suggest that G6PD plays an important role in downregulating EMT via modulation of miR‐200b in lung epithelial cells.Support or Funding InformationDepartment of Medical Biotechnology and Laboratory Sciences, College of Medicine, Chang Gung University, Tao‐yuan, TaiwanDepartment of Laboratory Medicine, Chang Gung Memorial Hospital, Lin‐Kou, Taiwan
Cystatin Peptide Prevents Alzheimer's Pathology in CRND8 AD Mice
Authors: Shaw Phyllis Ann 
Published: November 2023

Alzheimer's disease (AD) is the most common cause of dementia, and upwards of 25 million patients worldwide suffer from AD. The cost of AD care in the United States alone is $214 Billion and expected to reach $1.2 Trillion by 2050 as the population ages. It is thought that AD results from the accumulation of plaques and tangles in the brain leading to eventual neuronal death and cognitive decline. Amyloid‐beta 42 (Aβ42) is the main component of senile plaques. While there are current treatments to address the symptoms associated with AD and cognitive decline, there are no preventative or curative treatments to address the underlying pathophysiology. We identified a peptide capable of binding selectively to Aβ42. In the CRND8 mouse model of AD, intranasal delivery of the peptide reduced the number of Aβ42 plaques by 70–80% in the hippocampus and neocortex compared to scrambled control peptide. Using molecular modeling approaches, a second‐generation peptide was made to improve Aβ42 binding capabilities. The brains of AD mice with no treatment or scrambled peptide treatment had a large accumulation of amyloid beta aggregates and plaque in the neocortex and hippocampus. Importantly, a 4‐week treatment of AD mice with the second‐generation peptide shows a dramatic reduction in the Aβ plaque load in the hippocampus and neocortex. Preliminary behavioral studies suggest that intranasal delivery of the peptide may also improve cognitive function in the Morris Water Maze test. It is proposed that this peptide is a potential disease‐modifying therapy for AD that addresses the underlying pathophysiology.Support or Funding InformationThis work was supported by funds from NIH R21 (AG037448 ) awarded to PAS.
Drug Combinations Modulate Stem Cell Proliferation in the Subventricular Zone of 11‐month‐old Rats: Innate Gender Differences Could Explain Alzheimer's Susceptibility
Authors: Sulehria Tahir , Sharma Neelima , Gagle Samantha , Corbett Adrian M. 
Published: November 2023

In this study, we tested the effect of 30 days of various drugs and drug combinations on the stem cell proliferation in the subventricular zone (SVZ) of the lateral brain ventricles of middle aged (10–12 month) normal Sprague Dawley rats, looking for any gender differences. The female rats should be post‐menopausal, and showed very low endogenous stem cell proliferation, significantly different from male rats (P<0.0001). Statins (1 mg/kg) and the combination of Fluoxetine (5 mg/kg), Simvastatin (1 mg/kg) and Ascorbic acid significantly increased stem cell proliferation in the anterior and middle SVZ in female rats, while the three drug combination increased stem cell proliferation in the posterior SVZ. In the male rats, Fluoxetine (5 mg/kg) significantly decreased stem cell proliferation in all regions of the SVZ (anterior, middle, and posterior). Simvastatin (1 mg/kg) significantly decreased stem cell proliferation in the anterior SVZ in male rats, but not in the middle or posterior SVZ. When comparing the stem cell proliferation in different regions across the two genders with a 2‐way ANOVA, we found that fluoxetine and simvastatin significantly decreased male stem cell proliferation compared to females, but the drug combinations of fluoxetine and statin or fluoxetine, statin and ascorbic acid removed these gender differences. The decreased innate stem cell proliferation in females post‐menopause may make them more susceptible to Alzheimer's disease, but we have shown the fluoxetine, simvastatin and ascorbic acid might be used to increase stem cell proliferation, potentially delaying onset of the disease.Support or Funding InformationWSU Women's in Science Giving Circle
Thymoquinone Enhances Neurogenesis to A Greater Extent in Middle‐Aged Than in Young Aged Rat in Chronic Epilepsy
Authors: Brito Sijam Alassaf , Rao Muddanna Sakattu 
Published: November 2023

Neurogenesis in chronic epilepsy is known to be decreased significantly in a young aged, middle aged and aged rats. Thymoquinone (TQ), an active constituent of Nigella sativa seeds possesses anti‐inflammatory, neuroprotective properties and reported to enhance the neurogenesis in different CNS disease models. Aim of the study was to compare the efficacy of TQ in neuro protection immediately after status epileptics (SE), suppression of spontaneous recurrent motor seizures (SRMS) and aberrant mossy sprouting, and enhancement of neurogenesis, in young (4 months) and middle aged (12 months) chronically epileptic rats. SE was induced by intraventricular injection of kainic acid (0.5μg/ventricle) bilaterally in 4 months old and 12 months old male wistar rats(n=12 for each age group). These lesioned rats were treated with TQ (10 mg/kg; ip) for 4 days. A subgroup of lesion only (LO) and lesion+ TQ (L+TQ) rats were sacrificed at 5th day for analysis of hippocampal neurodegeneration by staining the brain sections with flurojade‐B. Remaining rats were video monitored between 2.5–3.0 months post SE for quantifying spontaneous recurrent motor seizure. Lesion only, Lesion+ TQ rats were sacrificed at the end of 3rd month along with normal and sham control rats. (n=6/group). Brain sections were stained with Fluro‐Jade B and labeled for doublecortin. The number newly born neurons and mossy fiber sprouting were quantified in the dentate gyrus at the end of 3rd month. TQ significantly decreased SRMS, reduced the neuron degeneration (25%), in CA1, CA3 and dentate hilus, suppressed the mossy fiber sprouting (30–40%) both in 4 months and 12 months age groups. TQ treatment increased the neurogenesis in both groups, however in middle aged rats it is significantly more than in young aged rats (P<0.001). Our results suggest that TQ is more effective in enhancing the neurogenesis in middle aged chronic epileptic rats than young aged chronic epileptic rats.Support or Funding Information(Supported by Kuwait University Grant #YM02/14).
Utility of Virtual 3D Animations and 3D Printed Models of Heart Development in Graduate Embryology Education
Authors: RICHARDSON ALISA , Lee Lisa MJ 
Published: November 2023

Visual demonstrations of embryological heart development have typically been presented in 2D images and more recently in scanning electron micrographs. As the heart developmental processes are highly complex both in time and space, the use of 2D visual aids have limitations and are not conducive to effective visualization of the heart looping and septation processes. The objective of this study was to determine the usefulness of virtual 3D animations and tangible, 3D printed heart models in graduate level embryology education. Five 3D virtual heart models were produced using Autodesk MAYA 2016™, each one depicting a different development stage. A virtual 3D animation was created using the virtual models to allow for a 360‐degree turn of each model, in order to provide an accurate depiction of the looping and septation processes. For tangible heart model production, a Markerbot 2 Replicator™ was used to print each virtual model in polylactic acid. The completed virtual animations and 3D printed models were made available to the first year graduate students enrolled in an introductory embryology course. A survey was conducted to gauge students’ perceived value of the virtual and tangible models of embryological heart development. Student exam performance on heart development topics was compared to the previous year's results to quantify educational value of the virtual and 3D printed models. When asked to compare the usefulness of the 3D animations versus the tangible models, students found the animations more useful and conducive to their learning. The quantitative analyses indicate that the 3D virtual animations and the 3D printed models hold promise in facilitating learning of the complex developmental processes in embryology education.Support or Funding InformationMaster of Science in Modern Human Anatomy, University of Colorado School of Medicine
The effect of the heavy metal nickel on the LINE1 endonuclease
Authors: Smith Michaela , Ahmad Idrees , Meyers Jade , Russell Brittany , Dorrah Kimberly , DeFreece Cecily 
Published: November 2023

The long interspersed element‐1 mobile element (LINE1) is a gene that encodes an enzyme protein called LINE1 endonuclease, which is known to nick DNA near adenine and thymine‐rich sites, resulting in double‐strand breaks and the subsequent retrotransposition, or movement, of the element into new genomic loci. Hyperactivity of this element within the human genome has been shown to potentially play a role in cancer‐causing mutations, such as breast and prostate carcinomas. The heavy metals nickel was tested on the LINE1 endonuclease to study the agent's inhibitory effects on the enzyme. Although nickel is a known carcinogen and environmental pollutant, the exact mechanism by which it induces cancer and illness remain unknown. In this experiment, assays were performed on the LINE1 endonuclease, using increasing concentrations of nickel. The data was analyzed using polyacrylamide gel electrophoresis to determine whether an increase in the amount of nickel present, had an effect on LINE1 endonuclease activity. We observed that nickel did not reduce LINE1 endonuclease activity. Resultantly, this could potentially provide a probable explanation for nickel's mechanism of action in certain cancers.Support or Funding InformationThis work was funded by an Institutional Development Award (IDeA) from the NIGMS under grant number P20GM103424 and from the Louisiana Cancer Research Consortium, the NIH‐RCMI grant #8G12MD007595‐05.
Human Milk Oligosaccharides in Preterm and Term Milk
Authors: Morrow Ardythe L , Chen Ceng , Cline Allison , Newburg David S 
Published: November 2023

BackgroundThe recommended food of preterm infants is milk from their own mothers, or, if not available, pasteurized donor milk, which typically consists of term milk from late lactation. Human milk oligosaccharides (HMOS) are important for microbial metabolism and infant health. Comparative studies of preterm and term HMOS are needed to guide neonatal nutrition practice.ObjectiveTo compare the HMOS from Cincinnati, OH mothers of infants who delivered preterm (<29 weeks gestational age [GA]) to those who delivered at term (39–42 weeks GA) in early and late lactation.MethodsMultiple milk samples were collected from Cincinnati mothers as part of the Global Exploration of Human Milk (GEHM) study, and their HMOS content was analyzed by LC‐MS. Milk collected from 10 to 23 days postpartum (Mo1M) was compared to mature milk (MatM) collected at 3 to 12 months postpartum. All 113 mothers of preterm infants and 118 mothers of term infants provided Mo1M (mean day at collection: 15.2 days – preterm, 16.5 days – term). Of the term mothers, 93 also provided MatM samples that we used to measure donor milk values. Donor milk varies in composition but typically consists of term MM.ResultsComparing preterm Mo1M to term MatM, composition was similar in total HMOS (3.6 and 3.2 g/L), though the acidic fraction of HMOS was higher in preterm Mo1M than term MatM (1.1 vs 0.6 g/L, p<0.05). But, term Mo1M differed from both preterm Mo1M and term MatM. HMOS concentration of term Mo1M was nearly 2‐fold higher than preterm Mo1M for total HMOS (6.1 vs 3.6 g/L, p<0.001), which held true for both neutral and acidic fractions of HMOS. Significantly (p<0.05) higher values for specific major HMOS were found for term Mo1M compared to preterm Mo1M and term MatM: 2′‐fucosyllactose (2′‐FL, 1.4 vs 0.6 vs 1.0 g/L); 6′‐sialyllactose (6′‐SL, 0.4 vs 0.2 vs 0.1 g/L); and disialyllacto‐N‐tetraose (DSLNT, 0.8 vs 0.2 vs 0.2 g/L). However, some HMOS, e.g., 3′‐sialyllactose (3′‐SL, ~0.2 g/L) maintained similar concentrations regardless of gestational age or timing of lactation.ConclusionsPreterm milk differs significantly from term milk in HMOS composition in the first month or later lactation, which represents most donor milk. The lower quantity of total HMOS in preterm than term milk should be examined in relation to preterm infant growth and health outcomes.Support or Funding InformationSupported in part by HD013021 and Mead‐Johnson
Effect of Soy‐Dairy Protein Blend Ingestion on Post‐Exercise Muscle mTORC1 Signaling and Protein Synthesis in Older Adults
Authors: Borack Michael , Reidy Paul , Husaini Syed , Markofski Melissa , Deer Rachel , Richison Abigail , Lambert Bradley , Cope Mark , Mukherjea Ratna , Jennings Kristofer , Volpi Elena , Rasmussen Blake 
Published: November 2023

PurposeOur previous work demonstrated that a soy‐dairy protein blend can prolong aminoacidemia and muscle protein synthesis in young adults following high intensity resistance exercise. The current work investigated the effect of the same soy‐dairy protein blend in older individuals who commonly develop anabolic resistance and sarcopenia. We hypothesized that a soy‐dairy protein blend (whey, soy and casein) would prolong aminoacidemia resulting in enhanced mTORC1 signaling and muscle protein anabolism as compared to a whey protein isolate (WPI) alone.MethodsThe study population for this double‐blind randomized controlled trial included recreationally active men 55–75 years of age. The subjects consumed 30g of WPI or 30g of a soy‐dairy protein blend (25% soy, 25% whey, and 50% casein) one hour following leg extension exercise (8 sets of 10 repetitions at 70% 1RM). Amino acid concentrations as well as basal and post‐exercise muscle protein turnover (breakdown and synthesis) were measured using stable isotopic methods. In addition, skeletal muscle mTORC1 signaling was assessed via western blotting.ResultsThere were no differences between the two protein groups for aminoacidemia, mTORC1 signaling or muscle protein turnover following resistance exercise and supplementation. Both groups showed similar blood branched‐chain amino acid profiles following protein ingestion (i.e., leucine, isoleucine, and valine remained elevated (p<0.001) for 240 min) and blood phenylalanine was increased for 185 min in both groups (p<0.001) post‐ingestion. Activation of the mTORC1 pathway (i.e., increased phosphorylation of mTOR, S6K1, and rpS6) was increased to a similar extent in both groups post‐exercise at early (0–2 hrs post‐supplement) and late (2–4 hrs post‐supplement) periods (p<0.05). FBR was significantly reduced post‐exercise for the WPI group (p=0.002) and tended to be reduced in the soy‐dairy protein blend group (P=0.077); however, no difference in post‐exercise FBR was observed between the two groups when controlling for resting FBR and age (p=0.31). Post‐exercise FSR was significantly elevated early for the WPI group (p=0.032), however, post‐exercise FSR did not differ between groups after controlling for resting FSR and age (p=0.38).ConclusionSoy‐dairy protein blend induced an increase in aminoacidemia, muscle protein synthesis and mTORC1 signaling to a similar extent as whey protein in older adults when 30 g of protein was ingested after exercise. This data adds new evidence for the use of soy‐dairy protein blends as targeted nutritional interventions that may help overcome anabolic resistance in an effort to counteract sarcopenia.Support or Funding InformationGrant support provided by DuPont Nutrition & Health
Evaluation of Different Delivery Vehicles on the Digestion and Absorption of Lutein using a Lymph Fistula Rat Model
Authors: Tso Patrick , Vurma Mustafa , Lee Dana , DeMichele Stephen 
Published: November 2023

Lutein delivered through breast milk is better absorbed by infants than lutein delivered in infant formula. We wish to better understand the possible absorption differences of lutein in breast milk versus infant formula by determining its bioavailability after gastric administration and to investigate whether the intestinal absorption of lutein can be improved by using new delivery vehicles. In STUDY ONE, we compared, under similar experimental conditions, the intestinal uptake, and the lymphatic and portal transport of lutein in conscious lymph fistula rats. Four groups of rats (n = 8–10/group) were randomized to receive via the gastric tube increasing doses (10 mg/kg, 20 mg/kg, 40 mg/kg, 80 mg/kg) of 20% lutein in safflower oil (SO) suspension to assess whether there was a saturable level of lutein that can be absorbed from the gastrointestinal tract. Aliquots of hourly portal blood and lymph were taken for lutein analysis. The dose response study showed that 20 mg/kg lutein was the saturable level of lymphatic lutein absorption with no lutein detected in portal circulation at any dosage level. In STUDY TWO, we randomized five groups of rats (n = 4–9/group) to receive 20 mg/kg lutein from either lutein in SO or from lutein in four different mono‐diglyceride oils (MDG). Gastric infusion of lutein suspended in MDG (20 mg/kg) significantly improved (71% – 211%; p<0.05) lymphatic lutein output 2–6 hours after lipid feeding versus lutein in SO. We conclude that a mixture of MDG helps solubilize lutein and facilitate gastrointestinal micelle formation thus improving lymphatic lutein absorption compared to triglyceride oils.Support or Funding InformationDK059630, Abbott Nutrition ZA34B