bluuebunny/crossref_metadata_2025 huggingface dataset:
In vivo visualization of cortical porosity development in an animal model of progressive chronic kidney disease
Authors: Buening Dorothy T , Allen Matthew , McNerny Erin
Published: November 2023

The effects of chronic kidney disease (CKD) on bone composition and structure is of interest due to the increased skeletal fracture risk observed in patients with CKD. The Cy/+ rat model of progressive polycystic kidney disease closely mimics the cortical bone loss and porosity observed in CKD patients. Our previous studies have shown increased and highly variable cortical porosity at 35 weeks of age in male Cy/+ rats, but the timing of the porosity's onset and its rate of progression were unknown. This study tested the feasibility of tracking the progression of CKD‐related bone porosity using longitudinal in vivo micro‐computed tomography (microCT) scans. MicroCT images of the distal tibia of normal and Cy/+ male rats were collected at 25, 30, and 35 weeks of age in order to visualize and quantify the developing porosity (Bruker Skyscan 1176, 9 micron resolution). A 1 mm volume of interest located 4 mm distal to the tibia‐fibula junction was chosen for analysis. Scans from 25, 30, and 35 weeks were 3D registered using SkyScan DataViewer preceding computational analysis allowing for a means to see and quantify the exact same locations and patterns of the porosity at various time points of the study. There was no significant difference in porosity between normal and CKD at either 25 or 30 weeks of age. At 35 weeks, CKD animals had significantly higher (11‐fold) cortical porosity compared to normal animals. A severe increase in cortical bone porosity was observed in the CKD animal model (see Figure 1). Although cortical bone loss occurred throughout the duration of the study, the majority of this bone loss occurred between 30 and 35 weeks (see Table 1). This experiment successfully applied in vivo microCT to monitor progressive bone loss in a CKD rat model, and it revealed that the severe but variable porosity previously observed in the Cy/+ rat appears after 30 weeks of age.

Support or Funding Information

Funding for this research was provided by the NIH F32DK108554 grant for Dr. Erin McNerny's post‐doctoral fellow research. Support for this project was received from Dr. John Davis at Alma College and Dr. Matthew Allen at Indiana University School of Medicine who established this summer internship exchange.

Cortical porosity of the distal tibia.

Time
Phenotype
Count
Mean Porosity (%)
Standard Deviation

25 weeks
CKD
10
0.42
0.29

Normal
8
0.40
0.26

30 weeks
CKD
11
0.50
0.47

Normal
16
0.36
0.15

35 weeks
CKD
13
2.51
3.24

Normal
18
0.23
0.08
A 3D Intervention Addressing Enzyme‐Substrate Interactions Misconceptions
Authors: Terrell Cassidy , Bongers Cassandra
Published: November 2023

Many students enter biochemistry courses with enzyme‐substrate interaction misconceptions stemming from prior biology and chemistry courses where this core concept is inadequately illustrated, explained, and/or assessed. Moreover, research has shown two‐dimensional representations not only fail to effectively convey biochemical concepts, but also propagate misconceptions. Reported enzyme‐substrate interaction misconceptions highlight the necessity for better, targeted instructional tools and assessments. We hypothesize that three‐dimensional (3D) physical models used in conjunction with targeted active learning assessments will increase student understanding of shape, stereochemistry, and electrostatic interactions involved in enzyme‐substrate interactions. We further propose that the use of these physical models will decrease the amount of time needed to complete the active learning assessments while also facilitating a deeper understanding of enzyme‐substrate interactions, therefore offering the instructor time to cover other course topics. This intervention study also addresses several biochemistry threshold concepts and supports the “Vision and Change in Undergraduate Biology Education: A Call to Action” report by offering concept‐oriented active learning opportunities.

A series of active learning assessments, with corresponding learning objectives and physical models designed by a team of undergraduate students, were developed to address the identified misconceptions of space, electronic interactions, and stereochemistry in enzyme‐substrate interactions. Here we aim to present (1) the design and development of these assessments and corresponding 3D physical models along with (2) the preliminary results of this study. In a control classroom, the active learning assessments were administered and video‐recorded in the absence of 3D physical models. After a second control semester, the physical models will be implemented simultaneously with the assessments into the classroom. In addition, the validated Enzyme‐Substrate Interaction Concept Inventory (ESICI) survey is administered at the beginning and end of each semester to establish a baseline for each class, measure gains in each of the three misconception areas, and offer a comparison against the published national average. Likert‐scale coded scoring of individual questions in the active learning assessments, ESICI results and observational evaluation of the recorded activities will be analyzed for the control and experimental classrooms using a mixed‐methods approach that includes quantitative inferential and descriptive statistical analysis. Preliminary data has been collected and analyzed on the first control semester in Spring 2016 and is planned for Fall 2016, suggesting that the need for this type of intervention is substantial. Further development and results of this study set the stage for curriculum wide development of enzyme‐substrate interaction targeted assessments.
Developing 3‐D Molecular Models to Highlight the Angiotensin II Type 1 Receptor and Olmesartan Binding for Medical and Educational Applications
Authors: Schmitt Lavin Emily F. , Merus Guy , Ramirez Valentina , Vohra Riti
Published: November 2023

Blood pressure regulation through the renin‐angiotensin system (RAS) is mediated through the activation and inhibition of angiotensin II (AngII) from its precursor angiotensin I (AngI). Activation of AngII leads to vasoconstriction, resulting in an increase in blood pressure, while AngII inhibition prevents vasoconstriction, causing a decrease in blood pressure. In humans, AngII binds to two subtypes of angiotensin G protein‐coupled receptors (GPCRs): AngII type 1 receptor (AT1R) and AngII type 2 receptor (AT2R). Almost all physiological and pathophysiological effects of AngII are mediated by AT1R, while the function of AT2R remains largely unknown. AT1R receptor blockers (ARBs), or sartans, are non‐peptide antagonists that act on behalf of the RAS cascade to inhibit vasoconstriction, thereby lowering blood pressure. Benicar™ is the most common brand of olmesartan, and in this study the interaction of this type of ARB with the angiotensin II AT1 receptor was modeled to depict the effects of angiotensin receptor blockers. The CBM‐SMART team (Center for Biomolecular Modeling ‐ Students Modeling A Research Topic) at Nova Southeastern University used 3‐D modeling and printing technology to examine structure and function relationships of the receptor and its antagonist. Details of the AT1R‐olmesartan structure from the Protein Data Bank file, 4ZUD, were imported into Jmol, a protein visualization software. Specific program commands were utilized in Jmol to manipulate the original file into a format that was later able to be 3‐D printed in order to create an instructional molecular model. The olmesartan anchors on the AT1 receptor were identified and noted on the model, consisting of amino acid residues Tyr35, Trp84, and Arg167. Additionally, three extracellular loops, as well as two disulfide bonds that contribute to the shape of the extracellular side of AT1R were emphasized. The amino acid residues Asp74, Asn111, and Asn 295 were highlighted in order to indicate the sodium‐ion binding pocket which is responsible for the intramolecular hydrogen bonding that regulates activation of AT1R. Developing 3‐D molecular models in this way is a relatively inexpensive process to visually represent important biological relationships that can be useful for students, professors, and physicians trying to understand complex molecular pathways.
Rare Bony Tunnel and the Middle Meningeal Artery
Authors: Bonatto‐Costa João Antônio , De Campos Deivis , Toillier Sabrina , da Silva Furtado Lucia Beatriz Fernandes , Rocha Andrea O , Malysz Tais
Published: November 2023

The middle meningeal artery is predominantly periosteal, irrigating the bone and dura mater. It enters the floor of the middle cranial fossa through the foramen spinosum, travels laterally through a middle fossa bony ridge, and curves anteriorly over the upper‐greater wing of the sphenoid where, at a variable point, it divides into parietal and frontal branches. The proximal segment of the frontal branch can be located in a bony tunnel and thus be particularly susceptible to tearing when the skull fractures. In addition, occasionally, the distal segment of the frontal branch may traverse a bony tunnel of variable size. To the best of our knowledge, there is no evidence in the current literature on the incidence of this rare bony tunnel. Thus, we decided to investigate the incidence of this bony tunnel in 85 adult skulls. In the studied sample, a significant tendency for this bony tunnel to be formed on the left side (p = 0.016). This paper also deals with some embryological aspects that may contribute towards explaining the formation of this bony tunnel.
Host Cell‐Zika Virus Interaction Determined by Envelope Protein Structure
Authors: Fassler Amy , Shah Roma , Khan Haania , Shukla Ayush , Schultz Kyle
Published: November 2023

Zika is a flavivirus similar to dengue and West Nile viruses. The Zika virus was first isolated in the Zika forest in Uganda in 1947. Rapid proliferation of Zika can be attributed to a lack of immunity and its unique protein structure. Once the virus enters the host cell, a change in pH causes a conformational change of the envelope (E) protein which releases the viral RNA into the cell. The E protein is a dimer in which each monomer is composed of three domains. Domain I contains a potential glycosylation site, an asparagine amino acid, at position 154. The sugar at this site may serve to bind the virus to host cells. In addition, glycosylation at this site may control the amount of solvent able to access the fusion loop in Domain II, affecting the wide array of cells the virus can infect. The five amino acids around the glycosylation site unique to Zika may also affect the virus's sensitivity to antibodies that bind the fusion loop. Because of Zika's mass proliferation and potential to cause birth defects, it has become a global health priority. An understanding of Zika structure and function may lead to development of vaccines targeting E proteins. The Marshfield High School SMART team 3D‐printed the ZIKV E protein highlighting the glycosylation site of Domain I to illustrate the host cell binding mechanism.
Structural and evolutionary insights from the reconstructed ancestral plant hydroxynitrile lyase, HNL1
Authors: Peterson Alison , Bunday Luke , Bussman Erika , Chadha Saahil , Ridler Jenna , Romashkova Elena
Published: November 2023

HNL1 is a reconstructed flowering plant hydroxynitrile lyase that is believed to have existed about 100 million years ago and displays promiscuity for esterase functionality. In other words, although HNL1 has low activity for an esterase function that hydrolyzes esters to an alcohol and acids, it is primarily a hydroxynitrile lyase, catalyzing the breaking of acetone cyanohydrin to acetone and cyanide (independent of water). The cyanide, produced through HNL1's lyase function, is released when herbivores wound the plant, thus acting as a natural defense mechanism. HNL1 allows us to see divergence in the evolutionary history of the alpha/beta‐hydrolase fold superfamily, a general class of hydrolytic enzymes with a core of variable numbers of alpha helices and beta strands. Indeed, HNL1 has a core of six alpha helices and six beta strands, and because it gave rise to several modern hydroxynitrile lyases (in plants such as the rubber tree, cassava, and wild castor) while retaining methyl esterase activity, we can explore the divergence between these two types of enzymes on the structural level. Specifically, we investigated how the reconstructed ancestral protein HNL1 phylogenetically relates to modern HNL and esterase proteins. The Minnetonka CBM SMART team used 3D modeling and printing technology to examine structure‐function relationships and the divergence of HNL1. Through the use of the Basic Local Alignment Search Tool (BLAST) provided by the National Center for Biotechnology Information (NCBI), we determined the percent similarity between protein sequences of the ancestral protein HNL1 and its modern counterparts. Then, this information was used to construct a phylogenetic tree in which HNL1's position at a specific node of special divergence was identified. Finally, while it is known that some of the amino acids in the active site are important for promiscuity, the specific identity and location of these amino acids within the protein are still actively being researched.
The Effect of Pueraria lobata/Rehmannia glutinosa on Improvement of Insulin Resistance and Lipid Metabolism in Ovariectomized Rats
Authors: Jeong Hye Yun , Kim You Jin , Kim Hyejin , Lee Won Jun , Kwon Oran
Published: November 2023

Menopause is a risk factor for diabetes and cardiovascular disease because estrogen deficiency has injurious effect on cardiovascular function and metabolism. Currently, there is an increasing requirement to develop strategies for improving estrogen deficiency‐induced cardiometabolic risks through non‐pharmacological interventions. The present study aimed to investigate the effect of a combination supplement of Pueraria Lobata/Rehmannia Glutinosa (PR) on the improvement of insulin resistance and lipid metabolism in an estrogen‐deprived animal model. Female Sprague‐Dawley rats (8 weeks old) were randomized into five groups: SC, sham operation + low‐fat diet (LFD); OC, ovariectomy (OVX) + LFD; OH, OVX + high‐fat diet (HFD); OHP, OVX + HFD + PR (400 mg/kg body weight); and OHS, OVX + HFD + estradiol (0.6 mg/kg body weight). Indices related to insulin resistance and lipid metabolism were determined in the blood, liver, muscle and adipose tissue. Furthermore, 1H‐NMR metabolites were measured in plasma and urine. The OVX resulted in an insulin‐resistant condition compared to the sham control, which was further aggravated by a HFD feeding. The PR supplementation significantly improved insulin responsiveness in adipose tissue, muscle, and the liver, leading to a restoration of metabolic flexibility. Adipose tissue became smaller, had more GLUT4 protein in membrane, less macrophage infiltration and higher hormone‐sensitive lipase mRNA expression. In addition, 1H NMR data revealed that carbohydrate, lipid, and amino acid metabolisms were influenced by PR in OVX rats. Taken together, the results of this study suggest that PR supplement has a potential to relieve insulin resistance and its related metabolic defects in postmenopausal women.

Support or Funding Information

This work was supported by the Bio‐Synergy Research Project (NRF‐2012M3A9C4048761) of the Ministry of Science, ICT and Future Planning through the National Research Foundation and the BK21PLUS through the National Research Foundation (22a20130012143).
Effects of a 3‐week moderate calorie restriction intervention on cerebral white matter connectivity in subjects with obesity
Authors: Kahathuduwa Chanaka Nadeeshan , Davis Tyler , O'Boyle Michael , Binks Martin
Published: November 2023

Objective

To examine the effects of a 3‐week 1120 kcal/d calorie restriction intervention on brain structural connectivity (measured using fractional anisotropy; FA) and region‐wise gray matter volumes (GM) in subjects with obesity.

Methods

Thirty‐two male and female subjects with obesity (19–60 years; 30–39.9 kg/m2) participated in a randomized, two‐group, repeated‐measures, 3‐week dietary intervention consisting of 1120 kcal/d from either total meal replacement (TMR; shakes) or typical diet (TD; portion control). Structural and diffusion tensor MRI were performed pre‐ and post‐intervention. Post‐ vs. pre‐intervention change in FA (ΔFA) and GM (ΔGM) were compared in the whole sample and between groups.

Results

Fifteen TMR and 13 TD subjects completed the intervention. Post‐ vs. pre‐intervention ΔFA or ΔGM was not significant within each group or between groups. In the whole sample, FA was increased in the right inferior fronto‐occipital fasciculus (IFOF; P = .005, inferior longitudinal fasciculus (P = .015) and uncinated fasciculus (P = .049) in post‐ vs. pre‐intervention comparison. ΔGM was not significant in pooled analysis.

Conclusions

Calorie restriction for 3 weeks appears to be sufficient to initiate changes in FA. Studies involving longer durations of calorie restriction are needed.

Support or Funding Information

The study was funded by Nestlé Health Science Inc.
A Randomized, Controlled, Crossover Trial to Assess the Acute Cognitive, Appetite, Glucose and Insulin Responses to Milk and Juice Beverages in Men and Premenopausal Women
Authors: Edirisinghe Indika , Palacios Orsolya M , Burton‐Freeman Britt , Spitznagel Mary Beth , Nieman Kristin M , Bell Margie , Maki Kevin C
Published: November 2023

The relationship between postprandial glycemic response and cognitive function is not clear, although some prior results suggest that an increase in postprandial blood glucose may improve aspects of cognition. The macronutrient profile of milk has been shown to elicit a lower glycemic response with less likelihood of a rebound drop below pre‐consumption level compared to other common beverages such as fruit juice. In addition, some findings indicate a link between appetite and cognition, and milk contains protein, which may affect satiety. Thus, the objective of this randomized, controlled, crossover study was to evaluate the acute glucose, insulin, appetite, and cognitive responses to intake of six commonly consumed beverages (water [control], skim milk, 1% milk, 2% milk, 100% apple juice or a combination of 100% apple juice and 2% milk) in healthy adults. Blood was drawn for glucose and insulin assessments and visual analog scale ratings were collected for fullness, hunger, desire to eat, prospective consumption, energy, and focus from pre‐beverage intake to 180 min post‐beverage intake. A cognitive function test battery was completed prior to and at 30, 90, and 150 min post‐beverage intake. A total of 61 subjects (32 men and 29 women) were evaluated with a mean age of 31.1 ± 1.1 y and a mean BMI of 26.4 ± 0.6 kg/m2. Results indicate that beverage type had a significant effect on median postprandial insulin (p < 0.001) and median net incremental area under the curve (niAUC0–180 min) ratings of hunger, fullness, desire to eat and prospective food consumption (p < 0.05 for all) but had no significant effect on focus, energy or glucose. Water intake resulted in significantly greater median niAUC0–180 min hunger ratings versus all other beverage types (p < 0.001 for all). For fullness, the median (interquartile range) niAUC0–180 min for water intake (−749 [−2817, 242]) was significantly lower versus intake of skim milk (0 [−1610, 1535], p = 0.005), 1% milk (149 [−806, 2270], p < 0.001), 2% milk (−117 [−2340, 1956], p = 0.021) and juice + 2% milk (−509 [−2893, 1213], p = 0.035). The intake of 1% milk (149 [−806, 2270]) significantly increased niAUC0–180 min for fullness compared with apple juice (30 [−2533, 1235], p = 0.047). None of the cognitive function domains were significantly affected by treatment condition or at specific time points, with the exception of the Simple Reaction Time at 30 min post‐beverage intake, where intake of 1% milk and 2% milk + juice resulted in faster reaction times compared to water (p = 0.024 and p = 0.023, respectively). In conclusion, beverage type significantly affected postprandial insulin and appetite, but not postprandial glucose or most measures of cognitive function.

Support or Funding Information

The Dairy Research Institute/National Dairy Council, Rosemont, IL
Whole Egg Increases High Density Lipoprotein‐Cholesterol (HDL‐C) Levels in Overweight Postmenopausal Women
Authors: Sawrey‐Kubicek Lisa , Zhu Chenghao , Stevens Allison , Randolph Jody , Sacchi Romina , Steinberg Francene , Zivkovic Angela M.
Published: November 2023

Despite recent changes in the US Dietary Guidelines indicating that dietary cholesterol is no longer a nutrient to be limited, the question of whether eggs should be part of a healthy diet remains controversial, particularly in populations at increased risk for cardiovascular disease. To address this question, a randomized, single‐blinded, crossover trial was conducted in 20 overweight and obese (BMI 25–35 kg/m2) postmenopausal women to compare the effects of whole eggs (equivalent to 2 large eggs/day) vs. egg whites in a breakfast meal on lipoprotein profiles. After a 2‐week lead‐in period all women consumed breakfast meals containing whole eggs and egg whites for 4 weeks each, in randomized order (10 starting with whole eggs, 10 starting with egg whites), with a 4‐week washout period between the two arms. Fasting blood samples and 4‐day diet records were collected at the beginning and end of each intervention period. Consumption of whole eggs was associated with a larger change from baseline (change in the egg arm minus the change in egg white arm) in the intake of dietary cholesterol, mean±SE: (394.9±13.7 mg), total fat (8.2±2.1%), and saturated fat (2.9±0.9%). Analysis of variance showed that HDL‐C increased significantly more during whole egg vs. egg white consumption (1.2±1.3 mg/dl vs. −1.6±1.4 mg/dl, p<0.05) whereas total cholesterol (TC) and LDL‐C did not change significantly. Six women, classified as dietary cholesterol hyper‐responders due to an HDL‐C increase in the upper quartile (ΔHDL‐C ≥9 mg/dl), had higher baseline total cholesterol (240.2±10.2 mg/dl vs. 207±8.1 mg/dl, p=0.02) and LDL‐cholesterol (156.3±8.9 mg/dl vs. 128.4±6.3 mg/dl, p=0.02) than hypo‐responders. The hyper‐responders also differed from hypo‐responders in baseline dietary cholesterol intake (184.2±20.3 mg/dl vs. 108.2±13.4 mg/dl, p=0.03), but did not differ in any other baseline dietary measurements or any baseline anthropometric measures including BMI, waist and hip circumference. The results of this study show that egg consumption is accompanied by a modest increase in HDL‐C in overweight/obese postmenopausal women without significant increases in TC or LDL‐C.

Support or Funding Information

The American Egg Board
Physiochemical properties, microstructure and probiotic survivability of symbiotic rice yogurt using polymerized whey protein as gelation agent
Authors: Guo Mingruo , Wang Cuina , Li Dan
Published: November 2023

A symbiotic rice yogurt using polymerized whey protein (PWP) as major gelation agent was developed. Physiochemical properties, microstructure, and probiotic survivability of the new product were analyzed. Rice to water ratio (RWR) of 1:3 (w/v) yielded the highest water absorption rate of 23.56% after soaking for 3 h at room temperature. The greatest degree of gelatinization (87.65%) was observed in rice samples parboiled at 80°C for 10 min at RWR of 1:12 (w/v). Addition of 0.05% (w/v) lecithin resulted in the most stable emulsion of rice milk. The finalized rice yogurt formulation was (w/v): rice milk, 1% rice protein, 1% prebiotic (inulin), 1% soy oil, 7% sugar, and stabilizers. The product was fermented at 43°C for 3.5 h with 0.01% ABY‐3 starter culture. The symbiotic rice yogurt contained 2% protein and 1.06% fat and exhibited good sensory attributes with an average score of about 4.3 (5‐scale). Both probiotics remained above 106 CFU/mL after 8 weeks. Microstructure analysis showed a compact and uniform network with small pores. Data indicated that the developed symbiotic rice yogurt was a novel functional food rich in protein and low in fat with good texture.

Support or Funding Information

The financial support for this project was provided by the Ministry of Science and Technology of China (Project # 2013BAD18B07).
Validation of a Macronutrient Mixed Challenge Beverage for Personalized Nutrition Applications using a Reduced Sampling Period
Authors: Winters Barbara L , Anthony Joshua C , Remensperger Allison , Boorsma Andre , Vandenbroek Tim , Maki Kevin
Published: November 2023

Oral carbohydrate, lipid and protein tolerance tests have been used to track changes in physiology, inform health status, and provide impetus for dietary changes. Tests typically take 4–8 hours, and require multiple blood draws, limiting the ability to use challenge testing outside of clinical settings for consumer wellness applications. The objective of this study was to validate the use of a mixed macronutrient challenge beverage using a truncated time course and reduced sampling protocol as part of a personalized nutrition and wellness program. Participants (n=18) were recruited from the general population for an IRB approved, double‐blind randomized study. Following on overnight fast, blood was collected via finger pricks and applied to dried blood spot cards, they then consumed the macronutrient mixed challenge beverage (20 g protein, 75 g carbohydrate and ≥50 % calories from fat (≥12 g fat/100 g) within 5 minutes of beverage consumption (t = 0 min) and finger prick blood samples were collected at 30, 60, 90, 120, 180 and 240 min. The mean ± SEM fasting triglyceride (TG) concentration was 112 ± 13.6 mg/dL, with a robust increase of 46 ± 12.7 mg/dL to 159 ±19.6 mg/dL at 120 min post beverage consumption, p=0.002. A gastrointestinal questionnaire was collected pre‐consumption and at 240 min. Overall the beverage was well tolerated and there were no significant increases from pre‐consumption in the percentage of subjects reporting somewhat more or much more than usual nausea, abdominal pain, flatulence, bloating or diarrhea. However, 14% of participants reported somewhat or much more than usual gastrointestinal rumblings (p<0.05) during the 240‐min period after beverage consumption. Collectively, these data show that the challenge beverage can be used to assess TG response at 120 min, and showed the feasibility of finger pricks for dried blood spot collection. These results support the view that challenge testing can be scaled for use in consumer wellness programs.

Support or Funding Information

Habit, LLC
Regional dietary adaptation of FADS genes in humans: molecular mechanism and functional consequences
Authors: Ye Kaixiong , Gao Feng , Keinan Alon
Published: November 2023

The fatty acid desaturase (FADS) genes encode rate‐limiting enzymes for the biosynthesis of omega‐6 and omega‐3 long chain polyunsaturated fatty acids (LCPUFAs). While LCPUFAs can be absorbed directly from meat‐ or seafood‐based diets, their biosynthesis is essential to compensate for their absence in plant‐based diets. Signals of regional adaptation have been reported for some genetic variants (e.g. an insertion‐deletion polymorphism rs66698963) in FADS genes, but a systematic evolutionary analysis for the genomic region encompassing the three FADS genes in global populations had been lacking. Here, we performed multiple statistical tests for the presence of natural selection on FADS genes in 22 global populations from the 1000 Genomes Project. We found three novel clusters of selection signals, two on FADS2 and one on FADS3, in multiple human populations. To elucidate the molecular mechanism of adaptive variants, we performed analysis of expression quantitative trait loci (eQTLs) in 44 tissues using data from the Genotype‐Tissue Expression (GTEx) project, unraveling regulatory effects of adaptive variants for FADS1, FADS2, and FADS3 in 12, 23, and 4 tissues, respectively. To characterize the functional consequences of adaptive variants, we examined genotype‐phenotype association using the GWAS Catalog and performed additional association analysis in the UK10K data set, revealing significant associations of adaptive variants with 46 traits. Specifically, recently adaptive alleles are associated with enhanced LCPUFAs biosynthesis and lower risk of inflammatory bowel diseases, consistent with the dietary needs of recent farmers and with the anti‐inflammatory effects of many LCPUFAs‐derived signaling molecules. We also identified two novel associations with Apo A1 and Apo B in the UK10K data set. Overall, our study demonstrated the regional adaptation of FADS genes to plant‐based diets by modulating gene expression and enhancing LCPUFAs biosynthesis.

Support or Funding Information

This work was supported by the National Institutes of Health (Grants R01HG006849 and R01GM108805 to AK) and the Edward Mallinckrodt, Jr. Foundation (AK).
Antiangiogenic Agent Nintedanib (BIBF 1120) Effectiveness in vitro and in vivo Against Prostate Cancer
Authors: da Silva Raquel Frenedoso , Raina Komal , Kumar Dileep , Dhar Deepanshi , Cagnon Valéria Helena Alves , Agarwal Chapla , Agarwal Rajesh
Published: November 2023

Nintedanib is a compound capable of inhibiting angiogenesis, preventing cell proliferation and decreasing tumor volume. This study was aimed at evaluating Nintedanib efficacy in prostate cancer (PCa) cell lines, besides morphological and molecular features in PCa development in transgenic adenocarcinoma of the mouse prostate (TRAMP) mice. PC3 and LNCaP cells were treated with either DMSO alone or Nintedanib (2.5, 5.0, 10 or 25 μM) in DMSO and assessed for viability and clonogenicity. Furthermore, male TRAMP mice were divided into control (Tween 20 (10%)) and treatment groups receiving Nintedanib (10mg/Kg/day) for 4 weeks. The animals were treated either from 8 to 12 weeks of age and euthanized both at 12 and 22 weeks of age or treated from 12 to 16 weeks of age and euthanized both at 16 and 22 weeks of age. At the end of the study, prostate ventral lobes were collected for structural, immunohistochemical and protein analyses for AR, ERα, FGF‐2, VEGF, microvessel density and proliferative index. Nintedanib treatment effectively decreased the total cell number and the survival of colonies. Morphological evaluation of TRAMP mouse prostate showed reduced number of lesions and the stromal hypertrophy after Nintedanib exposure. The treatment also caused a significant reduction in AR levels in epithelial cells and FGF‐2 in both prostatic stromal and epithelial cells. This was accompanied by a decrease in the microvessel density and VEGF immunolocalization. Furthermore, the proliferative index was also diminished by drug treatment. Nintedanib is effective against PCa in vitro and in vivo, due to the delayed neoplastic development in the glandular microenvironment and downregulation of multiple pathways involved in prostate tumorigenesis.

Support or Funding Information

Funding: FAPESP 2013/26677‐7

Ethics Committee 3285‐1
Determinants of gestational weight gain: The impact of diet, genes, and energy expenditure
Authors: Meng Ying , Groth Susan , Stewart Patricia
Published: November 2023

Background

Excessive gestational weight gain (GWG) has a long‐term impact on women's weight retention and contributes to the development of obesity in the mother and child. Many risk factors for GWG have been identified, but to date only 6%–33.8% of the variance in GWG has been explained.

Objective

The purpose of this study was to evaluate the overall variance of GWG that can be explained by adding resting metabolic rate (RMR) and a genetic score constructed on obesity‐related genes in addition to the sociodemographic and lifestyle factors.

Design

This study is an observational study of 55 African American women. Data collected or measured during pregnancy include: sociodemographic factors, medical information, lifestyle factors (i.e. dietary intake and physical activity), RMR, and seven obesity‐related genes. Linear regression was performed to evaluate the variance of GWG explained by potential risk factors listed above (e.g. prepregnancy body mass index, estimated gestational age, and gestational diabetes).

Results

The mean GWG was 32.6 (±17.3) pounds and 61.8% women gained above the Institute of Medicine GWG guidelines. The final multivariable regression model explained 65.5% (adjusted R2 = 0.566) of the variance in GWG. Five factors that explained the leading amount of GWG variance were total energy intake (10.9%, p=0.001), genetic score (9.7%, p=0.002), percentage of calories from fat (8.7%, p=0.003), RMR per kilogram body weight (4.1%, p=0.028), and parity (3.7%, p=0.035). The minor allele at rs7498665 in the SH2B1 gene also had a protective additive effect on GWG (p=0.04).

Conclusions

Dietary intake, the genetic score, and RMR were significantly associated with weight gain during pregnancy and explained a substantial amount of GWG variance.

Support or Funding Information

This work was supported by the National Center for Research Resources, a component of the National Institutes of Health grant KL2 RR024136‐03 and National Institute of Nursing Research grant K23NR010748.
Safety and efficacy of a novel KD120 MEC multi‐enzyme complex (N‐Sorb®) in human volunteers
Authors: Downs Berrnard W , Kushner Steve W , Bagchi Manashi , Swaroop Anand , Bagchi Debasis
Published: November 2023

Digestive enzymes have been historically consumed to enhance disintegration and dissolution of foodstuffs in the stomach. N‐Sorb is a novel KD120 multi‐enzyme complex (MEC) containing a range of protease, amylase, and lipase enzymes and including glucoamylase and alpha‐galactosidase. Unlike conventional digestive enzymes, these enzymes are activated in pH environments ranging from 6.5 to 8.5. These enzymes are encapsulated in a patent‐pending SK713 Soy Lecithin Phospholipid absorption technology (‘Prodosomes’) to facilitate rapid absorption and delivery into the blood, and increase availability to tissues. Eleven case studies from two independent clinics (one in California and one in Pennsylvania) are reported in this presentation under the strict supervision of two physicians. Eleven male and female volunteers (age: 20 to 71 years) suffering from gut related digestive problems including digestive dysfunctions and leaky gut, as well as gluten allergy, consumed a minimum of one dose (1/8 tsp Prodosomes and 1/8 tsp enzyme powder mixed into 4 ounces of water) two times per day on an empty stomach over different periods of time ranging from 1 month to 4 months. Subjects were compliant based on product usage and replacement. All subjects reported significant improvement in gastrointestinal functions among other systemic improvements. No adverse events were observed in these volunteers.

Support or Funding Information

VNI Inc, Lederach, PA, funded this research project
Higher serum carotenoid concentration associated with a lower incidence of metabolic syndrome in middle‐aged and elderly Chinese adults
Authors: Chen Yuming , Wang Cheng , Qiu Rui , Chen Geng‐dong , Cao Yi , Zeng Fang‐fang
Published: November 2023

Background

Several epidemiological studies revealed associations between carotenoids and the metabolic syndrome (MetS), but limited longitudinal cohort studies have been conducted to regard this association.

Objective

The objective of this study was to investigate whether serum carotenoids predict the incidence of the Mets and what is accounted for the associations by changes of lipids in a large population‐based study.

Method

We conducted a follow‐up study on 2773 men and women aged 40–75 years without Mets at baseline from the Guangzhou Nutrition and Health Study (GNHS). Blood pressure, waist circumference, blood lipids, glucose and other covariates data were collected in average every 3 years surveys. Serum carotenoids (α‐, β‐carotene, β‐cryptoxanthin, lycopene and lutein/zeaxanthin) were examined by HPLC at baseline.

Results

Over the average 5.4 years follow‐up, 1979 subjects with serum carotenoids assessed at baseline took part in the follow‐up survey at least once and 554 subjects developed new MetS during the follow‐up period. Inverse associations between serum carotenoids and the incidence of MetS were observed. After adjustments for confounders, HRs (95% CIs) of MetS for the highest (v.s. the lowest) quartile were 0.72(0.57, 0.90) for lutein/zeaxanthin, 0.39 (0.31, 0.51) for lycopene, 0.42 (0.32, 0.54) for α‐carotene, 0.45 (0.34, 0.56) for β‐carotene and 0.47(0.37, 0.61) for total carotenoids (all P‐trend <0.05). Other significant favorable associations between changes of HDLc with serum carotenoids were also revealed.

Conclusion

Our results revealed associations between higher serum carotenoid levels and a lower incidence of MetS in Chinese adults and the favorable influence of carotenoids might be partially driven by an improvement of serum HDLc.

Support or Funding Information

The present study was jointly supported by the National Natural Science Foundation of China (81472965, 81130052) and by the 5010 Program for Clinical Researches (No. 2007032) of the Sun Yat‐sen University (Guangzhou, China)
Impact of breast cancer diagnosis, personal characteristics and lifestyle factors on depressive symptoms
Authors: Judge Michelle Price , Julian Thomas , Wu Jing , Walter Jeanne , Irvin William J. , Starkweather Angela
Published: November 2023

Breast cancer (BCA) is associated with risk of an array of psychoneurological symptoms (PNS) including disturbances in sleep, anxiety, and depression. Lifestyle factors and personal characteristics, with potential impact on PNS, remain largely unexplored.

METHODS

A secondary exploratory analysis was conducted evaluating depressive symptoms in a cohort of women with stage I or II BCA during treatment for BCA and non‐BCA controls (n=58). Center for Epidemiologic Studies Depression Scale (CES‐D) assessments were observed at 3 time points (baseline, month 4 and month 9). With generalized linear mixed model and estimating equation approach the impact of cancer diagnosis, age, alcohol consumption, race, smoking, and BMI was evaluated related to CES‐D score.

RESULT

Breast cancer diagnosis (p=0.0298), smoking (p=0.0002), and mixed race identity (>1 race, p=0.0069) were significant predictors of CES‐D score. Age, alcohol consumption and BMI were not significant.

CONCLUSION

Women undergoing active treatment for BCA were at elevated risk for depressive symptoms supporting a need for more extensive evaluation and interventions for depressive symptoms during treatment for BCA. Additionally, smoking and mixed race identity, predictive of depressive symptoms, may compound risk in women with BCA. Further work is necessary evaluating the association of dietary factors with BCA depressive symptomatology.

Support or Funding Information

Research reported in this publication was supported by the National Institute of Nursing Research of the National Institutes of Health under Award Number P30NR011403. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Atractylodes Rhizome and Taraxacum Alleviate Colorectal Damage and Inflammation on DSS‐Induced Colitis in Mice
Authors: Kang Seunghee , Park Min Young , Kwon Oran
Published: November 2023

Inflammatory bowel diseases, including Crohn's disease and ulcerative colitis, are common chronic disorder of the gastrointestinal tract with a high prevalence rate worldwide. According to the Korean traditional pharmacopeia (Donguibogam), atractylodes rhizomes is among the most common ingredient to combine with taraxacum to treat intestinal dysfunction, providing a rationale to investigate the effect using modern technologies. In this study, we aimed to examine the effect of a combination of atractylodes rhizomes/taraxacum (AT) on maintaining gut health in by targeting the mucosal immunoinflammatory response in DSS‐induced colitis mice. Female Balb/c mice (7 weeks old, n=20) were randomly divided into four groups; normal control group (NC), DSS‐treated positive control group (DSS), AT treated group (A), and DSS + AT treated group (DA). AT (100 mg/kg/day) or placebo was administered by gavage for 14 days. For induction of acute colitis, mice received 3% of DSS dissolved in drinking water for last 7 days. Epithelial barrier permeability was significantly improved by AT administration, as measured by fluorescein isothiocyanate labeled dextran at the end of experimental period. Body weight, colon length, and disease activity index were significantly restored toward normal in the DA group compared to the DSS group. Histological analysis demonstrated that AT administration reduced cell destruction and inflammation of colon tissue. In parallel with these results, quantitative real‐time PCR analysis revealed that AT administration down‐regulated gene expression related to pro‐inflammatory activation (TNF‐α, IFN‐γ, IL‐1β, IL‐6, and COX‐2) compared with that in the DSS group. Further analysis of target gene expression related to cell proliferation/destruction, and mucin secretion is now on‐going. These results suggest that AT alleviates gut permeability, colon tissue destruction, and pro‐inflammation that was induced upon DSS stimulation.

Support or Funding Information

This work was supported by the Bio‐Synergy Research Project (NRF‐2012M3A9C4048761) of the Ministry of Science, ICT and Future Planning, and the BK21PLUS program (22a20130012143P of the Ministry of Education.
Fetal Alcohol Syndrome Effects in Retinal Cell Gene Expression and Development
Authors: Rodriguez Joseph A. , Muralidharan Pooja A. , Marrs James A.
Published: November 2023

Alcohol exposure during embryonic development has many adverse effects on development, and this is termed fetal alcohol spectrum disorder (FASD). Retinal development is consistently affected by ethanol exposure in animal models, and vision is frequently impaired in human patients. The zebrafish is an excellent model to study FASD due to their experimental accessibility and similar developmental pathways to humans. Previous studies show that ethanol exposure caused retinal cell differentiation defects leading to retinal defects, including photoreceptor defects. These defects persist in to juvenile stages, suggesting that the retinal stem cells are permanently altered. This research aims to understand gene expression changes that occur in retinal cells in the retina, and particularly the ciliary marginal zone (CMZ) stem cell compartment due to ethanolexposure. Zebrafish embryos exposed to ethanol [100, 150 mM EtOH], from 2–24 hours postfertilization (hpf), were grown in regular medium until 72 hpf. Eyes from ethanol treated and control zebrafish embryos were dissected and total RNA was isolated.. The RNA is then purified and then reverse transcribed into cDNA. Quantitative PCR was then used to analyze the cDNA using gene specific primers to determine relative expression levels of various genes present in the retinal developmental pathway. Experiments examined specific signaling pathways including, wnt, notch and proneural gene targets, and other specific markers expressed by retinal precursor cell and differentiating cell populations. This research will provide insight into gene expression changes affecting retinal development in specific cell types after alcohol exposure. Our goal is to understand the genesis of FASD birth defects caused by ethanol exposure, and this research will possibly identify ethanol toxicity targets and therapeutic strategies to prevent or reverse the damage.

Support or Funding Information

Research was supported by NIAAA.
Intact sodium caseinate and a sodium caseinate hydrolysate have potential to resolve inflammation through the cessation of proinflammatory signaling
Authors: Kirwan Anna , Daly Eimear , Nongonierma Alice B , Fitzgerald R.J , Roche Helen
Published: November 2023

Overweight metabolically unhealthy individuals are characterised by an unresolving chronic low‐grade inflammation which contributes to diseases such as insulin resistance and type‐2 diabetes (T2D) [1]. Dairy proteins have previously demonstrated potent anti‐inflammatory effects resulting in improved glycaemic management, however mechanistic perspectives are lacking [2, 3]. Our study investigates the anti‐inflammatory effects of sodium caseinate (NaCas) and a sodium caseinate hydrolysate (CasH) on cytokine production and inflammatory signalling pathways in an in vitro mouse macrophage cell model. J774.2 macrophages were treated with NaCas or CasH before stimulation with lipopolysaccharide (LPS). TNFα, IL‐1β, IL‐6 and IL‐10 cytokine secretion was determined by ELISA. NF‐κB and MAPK pathway proteins were analysed by western blot. NF‐κB activity in NIH‐3T3/NF‐κB‐luc cells was determined by luciferase assay. Both NaCas and CasH significantly reduced LPS and LPS/ATP induced TNFα and IL‐1β cytokine secretion in J774 macrophages without affecting cell viability. NaCas, and to a lesser extent CasH significantly reduces TNFα and IL‐1β cytokine secretion from BMDMs treated and stimulated with LPS ex vivo, but not TNFα secretion with LPS/IFN in combination. NaCas and CasH significantly reduce LPS induced NFκB transcription factor activity in a dose dependent manner. NaCas and CasH reduce IL‐6 cytokine secretion, with no reduction in IL‐10 with NaCas, but not CasH. Both NaCas and CasH reduced IκBα degradation and NFκBp65 phosphorylation. CasH significantly reduces the phosphorylation of ERK1/2 and p38, but not JNK. Thus, intact NaCas or hydrolysed CasH are potential new anti‐inflammatory ingredients with potential to prevent diseases of unresolved systemic inflammation, however further work is on‐going in terms of defining potential efficacy.

Support or Funding Information

This work was supported by Food for Health Ireland (Enterprise Ireland Grant: CC20080001).