bluuebunny/crossref_metadata_2025 huggingface dataset:
The Role of MeCP2 Mutations in a Reg‐Rett‐Able Syndrome
Authors: Arnholt Mark , Bertucci H. , Bertucci M. , Dorosz T. , Hart T. , Heimermann A. , Lentz M. , Rusch T. , Schultz J. , Weber N. , Weiss H. , Makky G.
Published: November 2023

Rett Syndrome affects about one in every 10,000 to 15,000 births. It is a genetic neurodevelopmental disorder that mainly occurs in females. Affected males die in infancy because the syndrome exhibits an X‐linked dominant pattern of inheritance. Rett Syndrome is caused by mutations in the X‐linked Methyl CpG binding protein 2 (MeCP2) coding gene. MeCP2 is necessary for epigenetic regulation of gene expression. This protein represses transcription by acting as a molecular bridge between methylated DNA and a complex of co‐repressor proteins including histone deacetylases and Sin3A. Mutations of MeCP2 cause overexpression of several genes during brain development. MeCP2 is a 52‐kDa protein with two functional domains: the transcriptional repressor domain (TRD) and the methyl‐CpG binding domain (MBD). Four notable amino acids found within the MBD are Arg106, Arg133, Phe155, and Thr158. Mutations at these four locations result in a decreased binding affinity of MeCP2 to methylated DNA: 2‐fold for mutated Thr158 and 100‐fold for the remaining mutated amino acids. The MBD has three beta sheets with Thr158 located on the c‐terminal end. Here, hydrophilic residues interact specifically with the methylated DNA. The Hartford Union High School SMART (Students Modeling A Research Topic) Team designed a model of MeCP2 using 3D printing technology to represent the MBD‐methylated DNA complex. The model highlights the amino acids involved in the interaction between MeCP2 and methylated DNA. Modeling the structure of MeCP2 allows for a more detailed understanding of the interaction between MeCP2 and DNA. This information will be crucial for designing treatments or interventions to improve the quality of life for Rett syndrome patients.

Support or Funding Information

This work was supported by the National Institutes of of Health Science Education Partnership Award (NIH‐SEPA 1R25OD010505‐01) and the National Institutes of Health Clinical and Translational Science Award (NIH‐CTSA UL1RR031973).
BRCA2's Role in Homologous Recombination Through Interaction with RAD51
Authors: D'Ausilio Morgan , Beckman Andrew , Brown Grace , Emeghara Udochi , Ho Felicia , Malzberg Ethan , Spellman Brandon , Tavan Ketaki , Xiao Jeffrey , Jensen Ryan
Published: November 2023

BRCA2 serves as a key mediator in error‐free DNA repair through homologous recombination (HR). Damaged DNA is repaired using identical portions of DNA from the sister chromatid which serves as a template for HR. BRCA2 binds RAD51, a recombinase capable of forming a nucleoprotein filament with single stranded DNA (ssDNA). BRCA2 then guides RAD51 to the site of DNA damage to catalyze the process of HR. BRCA2 has eight BRC repeats, which are highly conserved regions that bind multiple RAD51 molecules to promote nucleoprotein filament formation. The structure of BRCA2 BRC4‐RAD51 revealed that the BRC repeats are able to mimic the interaction of the RAD51‐RAD51 filament interface, providing a scaffold to nucleate filament growth. The Pingry School SMART Team, in conjunction with MSOE Center for BioMolecular Modeling, used 3‐D modeling and printing technology to further examine the structure‐function relationship of BRCA2 and RAD51. If BRCA2 is unable to bind RAD51 due to mutations, the resulting genomic instability can contribute to tumorigenesis. The Pingry School SMART Team aims to utilize the BRCA2‐RAD51 and the RAD51‐ssDNA filament structural models to investigate the roles of these proteins in HR and their link to breast and ovarian cancer.
Neuroglobin's Protective Role in Ischemic Stroke
Authors: Fangmann Julia
Published: November 2023

Stroke is the second most common cause of death, with cerebral ischemia causing 85% of strokes. Cerebral ischemia is a condition where the brain has inadequate blood supply. Less than five minutes of oxygen deprivation leads to neuronal cell death, harming brain structure and function. Neuronal hypoxia increases expression of a globin protein, neuroglobin (Ngb), near the hypoxic area. Ngb is a neuroprotective monomer made of 151 amino acids forming a typical globin fold with eight alpha helices. The Greenfield High School MSOE Center for BioMolecular Modeling MAPS Team used 3‐D modeling and printing technology to examine the structure‐function relationship of Ngb. Ngb has a heme group consisting of a porphyrin ring and an iron atom. The iron is hexacoordinated with the heme at four locations, with Ngb's distal residue His64, and with Ngb's proximal residue His96. The heme sits in a hydrophobic pocket formed by distal residues (His64, Phe28, Phe42, Tyr44, Lys67, and Val68) and proximal residues (His96, Leu92, Val99, Val101, and Phe106). Under normal conditions, oxygen binds to Ngb's iron atom, keeping the brain oxygenated. Cerebral hypoxia, as occurs in ischemic stroke, causes neurons to die and release oxygen, reactive oxygen species (ROS), and reactive nitrogen species (RNS). RNS and ROS are toxic byproducts of nitrogen and oxygen metabolism, respectively. Accumulation of RNS and ROS can damage DNA, RNA, and proteins and lead to cell death. Ngb protects surviving neurons by gathering RNS and ROS, allowing these byproducts to be converted into usable materials. Neuroglobin has a large cavity near its heme, formed by interactions between Val71 and Ala74, Leu85 and Tyr88, and Leu136 and Tyr137. This cavity allows ligands to access the iron for binding, either storing it for use later (oxygen) or removing it to be converted to prevent damage (RNS and ROS). The further study of neuroglobin and its protective nature could lead to the development of treatments for ischemic stroke.
Laxative Effect of Lotte Probiotic Chocolat© on Loperamide‐induced Constipation in Rats
Authors: Eor Juyoung , Tan Pei‐Lei , Yoon Seok‐Min , Choi Da‐Hye , Kim Sae‐Hun
Published: November 2023

Constipation is a common healthcare problem affecting all age groups throughout the world. Recently, dietary approach using probiotic intervention is increasingly recognized as a natural health improving supplement, attributed to their beneficial effects on gastrointestinal health. Probiotics, lactic acid bacteria strains, in particular, are frequently incorporated into fermented milk products, but other confectionery products are also widely available and potentially developed as functional confectionery products. It has been suggested that chocolate is an excellent protective carrier for optimal delivery of the bacterium into the colon, and could be an attractive alternative probiotic supplements for consumers. Despite these suggestions, little attempt has been made to incorporate probiotics into chocolate and to evaluate their potential applicability on gastrointestinal health. Thus, the potential gastrointestinal health benefits of Lotte Probiotic Chocolat© containing Streptococcus thermophilus MG510 and Lactobacillus plantarumLRCC5193 was investigated on rodents model with loperamide‐induced constipation. The constipated Sprague Dawley rats were induced intragastrically with loperamide (5 m/kg) for 7 days, followed by another 14 days of Lotte Probiotic Chocolat© treatment (2 × 1010 CFU/day). Colon and ileum was collected for biochemical and histopathological analysis. Meanwhile, fecal samples were collected for moisture content, appearance and microbiota analysis. Blood serum samples were also collected for biochemical analyses (TG, TC, MPO activity), respectively. Feeding of Lotte Probiotic Chocolat© to constipated rats were shown to increase fecal pellet number and moisture content, as well as modulate microbiota which is associated with constipation. Moreover, Lotte Probiotic Chocolat© treatment was capable of increasing the thickness of the colonic mucosa, colon muscle layer and the number of goblet cells, intestinal motility, and up‐regulating mRNA expression levels of ileum and colonic tight junction proteins altered by constipation. Additionally, Lotte Probiotic Chocolat© also exerted immunomodulatory effects, as demonstrated by a reduction of systemic inflammatory markers and improvement of the histological lesions in the colon. Altogether, these results demonstrate that Lotte Probiotic Chocolat© had significant positive effects on loperamide‐induced constipation and also in immunomodulatory alteration in colon region. Lotte Probiotic Chocolat© may be effective as dietary adjuncts for the treatment of constipation.
Effect of a High Protein, High Fiber Dietary Supplement on Subjective Appetite Ratings and Subsequent Ad Libitum Energy Intake in Overweight Men and Women
Authors: Sharafi Mastaneh , Wilson Michael , Alamdari Nima , Glynn Erin L.
Published: November 2023

Background

Protein and fiber have evidence supporting their function to promote satiety and improve subjective appetite ratings.

Objective

To determine the effect of a high protein, high fiber dietary supplement preload on appetite ratings and subsequent energy intake compared to an isocaloric high carbohydrate, low protein, low fiber placebo.

Methods

Participants (n = 25 male, 25 female) receive the dietary supplement (Shakeology) and the placebo on separate occasions, separated by at least 6 days, in a randomized, double‐blind crossover design. Subjects consumed the test product following a 12‐hour fast, and reported appetite ratings at 10, 20, and 30 min (visual analog scale (VAS)), followed by an ad libitum pizza meal to assess energy intake.

Results

Thirty‐eight individuals have completed the study. There were significantly greater reductions in VAS ratings of hunger, desire to eat, and composite appetite score, and a trend for reduction in ad libitum energy intake when subjects consumed the dietary supplement compared to the isocaloric placebo.

Conclusion

A high protein, high fiber dietary supplement (Shakeology) improves subjective appetite ratings in overweight men and women.

Support or Funding Information

This study was funded by Beachbody, LLC and conducted by an independent laboratory.
Prophylactic Effect of Lotte Probiotic Chocolat© Administration on Loperamide ‐ induced Constipation in Rats
Authors: Lee Chul‐Sang , Tan Pei‐Lei , Yoon Seok‐Min , Choi Da‐Hye , Kim Sai‐Hun
Published: November 2023

Constipation is defined as a stressful defecation which can lead to the risks of bowel obstruction and life‐threatening complications. Probiotics have received increasing attention as a natural way of promoting health and preventing diseases. Members of the genera Lactobacillus and Bifidobacterium, in particular; have been shown to promote gastrointestinal health through modulation of gut microbiota and gut immunity. Owing to their health‐promoting benefits, probiotic bacteria could be used for the treatment of constipation. It has also been suggested that chocolate can be used as a potential cryoprotectant candidate and carrier for delivering a probiotic formulation targeted to the colon. In previous studies, we found that consumption of Lotte Probiotic Chocolat© containing Streptococcus thermophilus MG510 and L.plantarum LRCC5193 improved symptoms of constipation in loperamide ‐ induced constipation rat model. However, very little work has addressed the potential protective effect of probiotic chocolate against constipation. Therefore, this animal trial was designed to investigate the potential prophylactic effect of Lotte Probiotic Chocolat© on loperamide – induced constipation in rats. Sixty Sprague Dawley rats were divided into six groups; N (no constipation), C (constipation), CHO (constipation + chocolate), Lotte Probiotic Chocolat© (constipation + chocolate + 1010 CFU/day of Streptococcus thermophilus MG510 and Lactobacillus plantarum LRCC5193), BB12 (constipation + chocolate + 1010 CFU/day of B. animalis subsp. lactis BB12), BL6 (constipation + chocolate + 1010 CFU/day of L. brevis subsp. coagulans). Feed and water was fed in ad libitum. The rats were treated for a total of 4 weeks and constipation was induced by daily loperamide (5mg/kg) administration at the fourth week. At the end of experiment, colon and blood serum were collected for biochemical and histological analyses. Additionally, fecal samples were also collected once a week during the pre‐treatment period, and three times in the constipation induction period for microbial profile analysis. Our results showed that MG510 + LRCC5193‐fed group had significantly (P< 0.05) higher mRNA expression levels of tight junction proteins (occludin, claudin, ZO‐1), thicker colonic mucosa and a higher number of goblet cells compared to the N and C groups. Moreover, MG510 + LRCC5193 group also had significantly (P< 0.05) higher motility score compared to the C and CHO groups. Fecal analyses also further revealed that administration of MG510 + LRCC5193 is not only increased and normalized fecal moisture content, but also altered the composition of gut microbiota. Hence, these results collectively demonstrate that 4 week administration of Lotte Probiotic Chocolat© can modulate the gut microbiota and improve intestinal functions in ways that could attenuate the risk of constipation.
Effects of Maternal High Folate and Low Vitamin B12 on DNA Methylation in Cord Blood Mononuclear Cells
Authors: Fard Anne , Plumptre Lesley , Tammen Stephanie , Akbari Mohammad , Sohn Kyoung‐Jin , Masih Shannon , Visentin Carly , Ly Anna , Berger Howard , Croxford Ruth , Choi Sang‐Woon , O'Connor Deborah , Kim Young‐In
Published: November 2023

DNA methylation is an important epigenetic determinant in gene expression, with potential consequent effects on disease susceptibility. During embryogenesis, new DNA methylation patterns of the fetus are established, which renders this period highly susceptible to environmental modifiers. Maternal dietary intake of folate and vitamin B12 has the potential to modulate DNA methylation via the provision of S‐adenosylmethionine. Maternal high folate and low B12 status has been linked to an increased risk of obesity and insulin resistance in the offspring. Using a cohort from the PREnatal FOlic acid exposuRe on DNA Methylation in the newborn infant (PREFORM) study (n=291 mother‐child pairs), global (total 5‐methylcytosine [5mC] content) and gene‐specific DNA methylation in cord blood mononuclear cells between newborn infants born to mothers with high RBC folate (>2860 nmol/L) and low B12 (<167 pmol/L) concentrations and controls born to mothers with lower RBC folate (<2860 nmol/L) and higher B12 (>167 pmol/L) concentrations were investigated using liquid chromatography/mass spectrometry (LC/MS‐MS) and Illumina CpG methylation microarray, respectively. Infants from ‘high folate/low B12’ mothers had 6.2% lower 5mC content than infants from ‘moderate folate/marginal to adequate B12’ mothers (5.16±0.277 % vs. 5.50±0.411 %; p=0.0069). Furthermore, infants from ‘high folate/low B12’ mothers were 9% heavier than infants from ‘moderate folate/marginal to adequate B12’ mothers (3697±455 g vs. 3393±S451 g; p=0.001). These data suggest that maternal folate and B12 status can influence global DNA methylation in the developing fetus and can potentially induce phenotypic changes in the newborn infant. Studies are underway to determine gene‐specific DNA methylation changes in cord blood mononuclear cells associated with maternal folate and B12 status and their functional ramifications.

Support or Funding Information

Funded by: CIHR (MOP# 106446)
Pentosidine, an Advanced Glycation End Product, Is a Negative Predictor of Cortical Bone Geometric Endpoints in Children
Authors: Kindler Joseph M , Liu Weixi , Dain Joel , Laing Emma , Lewis Richard M
Published: November 2023

Advanced glycation end products (AGEs) are suspected to contribute to the increased fracture risk in adults with type‐2 diabetes. In addition to being directly implicated in skeletal fragility, AGEs may adversely influence bone turnover, and consequently, bone mass and geometry. To date, no AGE and bone data have been reported in children. Therefore, the objective of this pilot study was to examine relationships between the AGE pentosidine and cortical bone geometric outcomes in children. Participants were 39 black and white boys and girls (ages 8–13 years) who were in the early stages of sexual maturation. Tibia and radius cortical bone (66% site relative to the distal growth plate) was assessed via peripheral quantitative computed tomography. In fasting sera, insulin (via RIA), glucose (via enzymatic Autokit glucose method), and pentosidine (via ELISA) were measured. The homeostasis model assessment of insulin resistance (HOMA‐IR) was calculated. Linear regression analyses were performed to predict metabolic and cortical bone endpoints from pentosidine. All analyses included race, sex, and sexual maturation rating stage as covariates. For analyses involving cortical bone, muscle cross‐sectional area was included as an additional covariate. Serum insulin (β = 0.346, P = 0.034), but not glucose (β = −0.03, P = 0.866) or HOMA‐IR (β = 0.317, P = 0.056), was a positive predictor of pentosidine. Pentosidine was a negative predictor of tibia cortical bone mineral content (β = −0.266, P = 0.043) and cortical bone area (β = −0.282, P = 0.028), as well as radius total bone area (β = −0.248, P = 0.024), cortical bone area (β = −0.254, P = 0.040), periosteal circumference (β = −0.236, P = 0.033), and polar strength strain index (β = −0.220, P = 0.048). In contrast, pentosidine was positively correlated with radius cortical volumetric bone mineral density (β = 0.347, P = 0.045). We report the first data in children to show inverse relationships between the AGE pentosidine and metabolic and cortical bone geometric endpoints. The role of AGEs, such as pentosidine, warrants further investigation within the context of the increased fracture risk in obese children.

Support or Funding Information

This research was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development Grant RO1HD057126, by the Allen Foundation grant 2.008.319, and by the University of Georgia Agricultural Experiment Station, HATCH projects GEO00797 and GEO00700.
Determining Toxic Levels in Pre‐implantation Mouse Embryo Development from Exposure to Electronic Nicotine Delivery System (e‐Cig) Carrier Fluid
Authors: Hamm David Michael , Pietrangelo Michael Anthony , Swanson Robert James
Published: November 2023

Electronic Nicotine Delivery Systems (ENDS or e‐cig), are increasingly popular, despite not well FDA regulated. With increased trends in ENDS usage, especially as a “safer” alternative to cigarettes, the potential damage due to other chemicals in the ENDS carrier fluid (CF) must be determined in the absence of nicotine for both non‐vaporized (NCF) and vaporized (VCF) material. The main components of this CF are propylene glycol, vegetable glycerin, and flavor additives. Gas Chromatography/Mass Spectroscopy was used to determine the components of ENDS/NCF and ENDS/VCF. Our data establish a relationship between pre‐implantation embryo exposure to ENDS NCF and VCF relative to embryo development in a murine model. ENDS/NCF was placed in the e‐cig and then removed; ENDS/VCF was placed in the e‐cig, vaporized, and then condensed back to fluid using a glass‐bead‐filled, 7mm diameter × 7m long, copper coil at 2°C. A single 2‐cell embryo was placed in each well of a 96 well culture plate, in triplicate experiments, with modified Krebs bicarbonate‐buffered embryo growth medium (mKBBM) as mKBBM/NCF or mKBBM/VCF mixtures. The mKBBM/NCF was initially tested at 0.0% (control), 0.1%, 0.3%, and 0.5% concentrations by volume. The mKBBM/VCF was tested at 0.0, 0.001, 0.01, 0.6, 1.6, 2.6, and 3.6 percent concentrations by volume. Embryos were incubated for 96 hours (hrs) during continuous exposure and morphological observations were made every 24 hrs. This mouse embryo assay (MEA) has been used for IVF toxicity testing with passing minimum values of 20% morula‐65% blastocyst (85% combined) growth rate at 96 hrs. In the NCF group, control embryos passed the MEA (89%) while 0.1%, 0.3%, and 0.5% failed (84%, 0%, and 0% respectively). In the VCF group, 0.0, 0.001, 0.01 and 0.6% embryos passed the MEA (100% for all but 0.6% which was 87%) while the 1.6%, 2.6%, and 3.6% failed the MEA (80%, 80%, and 16% respectively). Experiments with identical percentages for both NCF and VCF are currently being performed. Additionally, a one‐way ANOVA with TUKEY posthoc, α = 0.05, was performed to evaluate null hypothesis of no difference based on exposure and viability. This revealed significant differences between groups at 24, 72, and 96, but not at 48 exposure hrs. These results indicate an initial developmental delay in the first 24 hrs with an adaptive catch‐up growth phase from 24–48 hrs followed by a drop‐off in growth post 48 hrs of CF exposure. Farsalinos, et al., 2015, estimated 3mL of e‐liquid/day; 0.00000375% per 80kg man, well below our concentrations but we did not include nicotine in our experiments. Study animals were on IACUC‐approved protocol #11.161107.

Support or Funding Information

Center for Research, Liberty University College of Osteopathic Medicine
The Effects of Mixed Nuts on Lipid Profiles, Glucose, Oxidative Stress, and Antioxidant Capacity in Atherogenic‐Diet Fed Rats
Authors: Groven Shauna L , Corwin Caitlin , Marx Amanda , Messervy Luke , Hooshmand Shirin , Kern Mark , Lee Yoonhee , Hong Mee Young
Published: November 2023

Cardiovascular disease (CVD) has become the leading cause of death in the United States, and is primarily caused by atherosclerosis, which occurs when LDL‐cholesterol is oxidized within endothelial walls of the arteries. Animal and human studies have both demonstrated that dietary intake of nuts improves blood lipid profiles, which may decrease CVD risk. Contributing factors include low saturated fat to high unsaturated fat ratios in nuts, as well as high concentration of fiber and various vitamins, minerals, and polyphenols. While numerous studies have examined the effects of certain types of nuts, limited research exists regarding the potential benefits of nut mixture consumption. Therefore, the objective of this study was to determine the effects of mixed nuts on lipid profiles, glucose, oxidative stress, and antioxidant capacity in rats fed atherogenic diets. Thirty male Sprague‐Dawley rats (21‐days old) were randomly divided into three groups of ten based on initial body weight, consuming either an isokilocalorie control diet (no nut), 8.1% pistachio diet (single nut), or 7.5% mixed nut (almonds, cashews, pecans, pistachios, walnuts, peanuts, macadamia nuts, and brazil nuts) diet for 8 weeks. Initial body weight, final body weight, weight gain, daily food intake, and daily water intake were not statistically different between the three groups. Both pistachio and mixed nut groups significantly decreased triglycerides (p=0.023), total cholesterol (p=0.037), LDL‐cholesterol (p=0.010), and oxidative stress (p=0.014), and increased total antioxidant capacity (p=0.046) compared to the control group. No significant differences in organ weights, albumin, blood glucose, HbA1C, or HDL‐cholesterol were found between groups. No significant differences existed between pistachio and mixed nut groups. Therefore, this study suggests that consumption of nut mixtures yields similar benefits to those reported for various individual types of nuts with regard to risk factors for CVD, including lipid profiles, oxidative stress, and total antioxidant capacity in atherogenic‐diet fed rats.

Support or Funding Information

The study was funded by American Heart Association (16GRNT31360007) and supported by San Diego State University N302L Advanced Nutrition Laboratory.
Establishment of Rat Model of Hyperuricemia and Efficacy Evaluation of Positive‐Control Drugs
Authors: Huo Jiao , Lu Yedan , Yang Hua , Ma Sijia , Cheng Weibo , Chen Jinyao , Zhang Lishi
Published: November 2023

Objective

Hyperuricemia, caused by dietary, environmental and genetic factors, has been recognized as a high risk factor for gout, cerebrovascular and cardiovascular diseases. Most hyperuricemic animal models were carried out on rats with short‐term treatment (<1~15 days), which were not appropriate for screening of drugs with long‐term mechanisms of action. The aim of this study was to explore the strength and weakness of different doses and combination of several hypericemia‐inducing drugs that can be used for establishment of chronic hyperuricemia model in rats, and to screen the effective positive control drugs, therefore to provide a test platform for hyperuricemia prevention and control.

Methods

130 male SD rats were randomly divided into 10 groups, i.e. a control group, 3 model groups and 6 positive groups. The rats were administrated with different model drugs in different doses by oral gavage. Model 1 was administrated with 100.0 mg/kg.bw adenine+1.50 g/kg.bw oteracil potassium; model 2 was administrated with 50.0 mg/kg.bw adenine+1.50 g/kg.bw oteracil potassium; model 3 was administrated with 1.50 g/kg.bw oteracil potassium only. Each model group has two positive drug intervention sub‐groups (allopurinol 27.0 mg/kg.bw and benzbromarone 4.5 mg/kg.bw respectively), together 6 groups. The model drugs were administrated at 9:00 am and the positive control drugs were administrated at 3:00 pm in all groups for continuous 45 days. Serum uric acid (UA), creatinine (CR) and urine nitrogen (BUN) were detected on day 15, 30 and 45. Histopathological analysis of liver and kidney was carried on day 45 after sacrificing.

Results

The level of serum UA in the three model groups was significantly higher than in the normal control group in a time‐dependent pattern. Levels of CR and BUN in model 1 and model 2 control sub‐groups were significantly higher than those in the normal control group. Allopurinol could reduce serum uric acid levels in all three models, while benzbromarone only had effect on model 3. Obstructive nephropathy was discovered in model 1 and model 2. However, the kidney injury, to some extent, could be reversed by allopurinol.

Conclusion

The results from this study indicated that combination of 50.0 mg/kg.bw adenine and 1.50 g/kg.bw oteracil potassium could be available to establish a stable chronic hyperuricemia rat model, and allopurinol could be an appropriate positive drug for hyperuricemia relieving in this model.

Support or Funding Information

This work was supported by science and technology projects for youth of traditional Chinese medicine, Sichuan province [Grant Number 2016Q045]
Tartary Buckwheat Extract Reduces Lipid Accumulation and Inflammation in 3T3‐L1 Adipocytes
Authors: Lee Eunyoung , Lee Mak‐Soon , Shin Yoonjin , Jung Sunyoon , Kim Seog‐Young , Park Seonyoung , Yun Min‐Kyu , Lee Sung‐Jin , Sohn Johann , Yu Heui‐Jong , Lee Yoo‐Hyun , Kim Yangha
Published: November 2023

The aim of this study was to compare the effects of 50% ethanolic extracts (TB‐50) and 70% ethanolic extracts (TB‐70) of tartary buckwheat on adipogenesis and pro‐inflammatory cytokines in 3T3‐L1 adipocytes. In comparison with TB‐50, TB‐70 exhibited higher efficiency in inhibiting the intracellular lipid accumulation and triglyceride contents. Glycerol‐3‐phosphate dehydrogenase (GPDH) activity also decreased in TB‐70‐treated cells, compared to TB‐50‐treated cells. In TB‐70‐treated cells, mRNA levels of adipocytes‐specific genes such as peroxisome proliferator‐activated receptor‐γ (PPAR‐γ), CCAAT/enhancer binding protein‐α (CEBP‐α), adipocyte protein 2 (aP2), acetyl‐CoA carboxylase (ACC), fatty acid synthase (FAS), and stearoylcoenzyme A desaturase‐1 (SCD‐1) were significantly lower in comparison with TB‐50‐treated cells. In addition, TB‐70 was significantly decreased the mRNA levels of pro‐inflammatory cytokines such as tumor necrosis factor‐α (TNF‐α), interleukin‐6 (IL‐6), and monocyte chemoattractant protein 1 (MCP‐1), and TB‐50 did not. These results suggest that TB‐70 may have higher efficacy on the inhibition of adipogenesis and pro‐inflammatory cytokines than TB‐50. These effects of TB‐70 were partially associated with an inhibition of GPDH activity, and down‐regulation of the adipocyte‐specific genes and pro‐inflammatory cytokines in 3T3‐L1 adipocytes.
A prospective investigation of coffee drinking and bladder cancer incidence in the United States
Authors: Loftfield Erikka , Freedman Neal D. , Inoue‐Choi Maki , Graubard Barry I. , Sinha Rashmi
Published: November 2023

Background

In 1991, coffee was classified as a Group 2B carcinogen, possibly carcinogenic to humans, based on limited epidemiological evidence of a positive association with bladder cancer. In 2016, the International Agency for Research on Cancer downgraded this classification due to lack of evidence from prospective studies particularly for never smokers.

Methods

Baseline coffee drinking was assessed with a food frequency questionnaire in the NIH‐AARP prospective cohort study. Among 469 047 US adults, who were cancer‐free at baseline, 6012 bladder cancer cases (5088 men and 924 women) were identified during >6.3 million person years of follow‐up. Multivariable‐adjusted Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI), with non‐coffee drinkers as the reference group.

Results

Coffee drinking was positively associated with bladder cancer in models adjusted for age and sex (HR for ≥4 cups/day relative to coffee nondrinkers=1.91, 95% CI=1.70–2.14; P‐trend<0.0001). However, the association was substantially attenuated after adjustment for cigarette smoking and other potential confounders (HR for ≥4 cups/day relative to coffee nondrinkers=1.18 95% CI=1.05–1.33; P‐trend=0.0007). Associations were further attenuated after additional adjustment for lifetime smoking patterns among the majority of the cohort with this available data (P‐trend=0.16). There was no evidence of an association among never smokers (P‐trend=0.84).

Conclusions

Positive associations between coffee drinking and bladder cancer among ever smokers but not never smokers suggest that residual confounding from imperfect measurement of smoking or unmeasured risk factors may be an explanation for our positive findings.

Support or Funding Information

This work was supported by the Intramural Research Program of the National Institutes of Health (NIH), Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Department of Health and Human Services.
Large hadrosaurid dinosaur from the San Juan Basin, New Mexico
Authors: Carrillo Noell , VanZant Ashley , Guenther Merrilee
Published: November 2023

Hadrosaurid dinosaur diversity in the San Juan Basin of New Mexico has been difficult to determine due, in part, to poor preservation of specimens compared to those found in northern North America. A reexamination of a collection of hadrosaurid material from the Hunter Wash Member of the Kirtland Formation in San Juan County, New Mexico, excavated in 1922 by Charles H. Sternberg, has revealed some well‐preserved specimens. Among these specimens is a large hadrosaurid humerus that is 860 millimeters in length, with a humeral shaft diameter of 176 millimeters. The proportional size of the deltopectoral crest in relation to the humeral shaft indicates that the humerus comes from a saurolophine hadrosaur.

Previously recognized hadrosaurid diversity in the lower Kirtland Formation has been restricted to the lambeosaurine, Parasaurolophus cyrtocristatus, and the saurolophine, Kritosaurus navajovius. Recent studies of hadrosaurid elements in this Sternberg collection have indicated that there are additional, as yet unnamed, saurolophine taxa in the San Juan Basin with strong affinities to the Kritosaurini, but distinct from K. navajovius. The large humerus is significantly larger than that of any of the previously known hadrosaurid taxa from the lower Kirtland Formation, including the newly described kritosaurine material. Morphometric analysis of the humerus suggests an element with proportions similar to those of Shantungosaurus, one of the largest hadrosaurs, and dissimilar to any of the previously known San Juan Basin hadrosaurid taxa. The robust construction of the humeral shaft is reflected by a shaft volume to humeral length ratio that greatly exceeds most other hadrosaurid taxa, resulting in a humerus with greater loading capacity. Though it is an isolated element, this humerus provides evidence that there were large hadrosaurids, potentially from a new species, living in the San Juan Basin, expanding the diversity of the San Juan Basin hadrosaurid dinosaur fauna.
Turmeric Dietary Supplement‐Induced Autoimmune Hepatitis: A Case Report
Authors: Funk Janet , Alfafara Chelsea , McEvoy Sean , Strom Meghan , Lukefahr Ashley
Published: November 2023

Autoimmune hepatitis (AIH), a chronic disorder of unknown etiology characterized by hypergammaglobulinemia and autoantibody positivity, is induced by drug injury in a minority of cases. Herbal supplements are increasingly being recognized as a potential cause of drug‐induced hepatitis (DIH). We report here on a case of drug‐induced, autoimmune hepatitis (DIAIH) attributable to ingestion of a turmeric dietary supplement. Autoimmune hepatitis (AIH) was diagnosed, as per Hennes criteria (score = 7 of 8 total), in a 76‐year old Caucasian woman presenting with an asymptomatic elevation in liver transaminases (alkaline phosphatase and bilirubin, normal). Diagnostic work up was notable for: 1) elevated IgG levels (1.3 X ULN); 2) positive antibody titers (> 1:80) for atypical pANCA and smooth muscle actin; 3) liver histology on biopsy compatible with AIH, and 4) exclusion of viral hepatitis. The patient's medical records, while not including mention of turmeric dietary supplement use, did document concurrent use of 15 other prescription or over the counter (OTC) medications which remained unchanged throughout the course of transaminase elevations. Attribution of AIH to turmeric supplementation, which the patient had begun 10‐months prior to her diagnosis, was elucidated by the patient, who stopped turmeric supplementation 2 months after her AIH diagnosis upon reading of a possible risk of turmeric‐induced hepatitis. Within 1 month of turmeric discontinuation, transaminase levels, which had risen to a maximum of 4–8 X ULN (for AST and ALT, respectively) began to decline and returned to normal within a year, where they have remained until the present time (3 years). Assessment of updated RUCAM drug‐induced hepatitis (DIH) criteria (Danan et al, Int J Mol Sci 17:2016) yielded a score of 6 (of 13 total, with ≥9 being highest category of attribution [“highly probable”]), consistent with probable attribution of turmeric use to hepatic injury in this patient. As is common in situations of supplement induced side‐effects, the actual product, which the patient had taken as directed on the label, was not identified or available for testing. In summary, this case illustrates several key points: 1) consumers and healthcare professionals should be aware that turmeric supplements, a top selling herbal in the US, can be associated with hepatoxicity, including induction of AIH; 2) the role of turmeric, concomitant medications, and/or potential contaminants in mediating supplement‐induced liver damage cannot be assessed at present; and 3) open conversations about OTC supplement use between healthcare providers and patients remains imperative to ensure delivery of high quality practice, particularly in situations of increased risk of drug‐supplement interactions.

Support or Funding Information

NIH‐NCCIH#R34 AT007837
A Web‐based Binge Eating Disorder Intervention Program Reduced Eating Disorder Risks in Overweight or Obese Females–A Pilot Study
Authors: Yu Zhiping , Snyder Jill , Stuart Katie , Wilburn Jennifer , Pudwill Holly , Williams Brittnee , Cortazzo Kristen
Published: November 2023

Objective

Those who suffer from eating disorders including Binge Eating Disorder (BED) face many hurdles including lack of access to treatment, guilt, denial, lack of motivation to change, and shame. The fear of stigmatization can also prevent those who suffer from eating disorders from seeking proper treatment. Web‐based treatment programs present an opportunity to eliminate or reduce some of these hurdles and resistance to treatment. The current Randomized Controlled Trial aimed to assess the efficacy of a web‐based outpatient treatment program in overweight and obese females diagnosed with BED.

Methods

A total of 18 overweight or obese women with clinical or sub‐clinical binge eating disorder, aged 20–73, were randomized into either a face‐to‐face treatment program or a web‐based treatment program. Twelve participants completed the study. In face‐to‐face group (n=8), participants received a total 12 session counseling including an individual biweekly session with a psychotherapist and biweekly session with a Registered Dietitian (RD) specializing in eating disorders. In the web‐based group (n=4), participants received a 12‐session weekly video counseling through an online telemedicine software with psychotherapist and RD. Outcomes were assessed at 3 months including weight, binge episode (BE), and Eating Disorder Examination (EDE) questionnaire that assess eating disorder risks.

Results

In the end of study, there were no differences in weight change and binge episodes change between two treatment groups. When comparing before and after treatment, participants did not lose weight in both groups. Participants in Face‐to‐face group reduced binge episodes (P<0.01) but not in web‐based group. Better improvements were observed in web‐based group for EDE shape concern (p=0.01), weight concern (p<0.05), and global score (p<0.05) than face‐to‐face group.

Conclusion

Web‐based treatment program could potentially be an effective approach for binge eating disorder patients. Large scale randomized clinical trials are warranted to further assess the efficacy of web‐based approaches in treating eating disorders.

Support or Funding Information

Us Women and Girls' Health Endowed Research Professorship; Complimantory telemedicine software from Fruit Street Company
Examining Normative Values in Wearable Device Bite Count Data from a One‐Week Free‐Living Intervention
Authors: Beatty Jacqueline , Mayette Gregory , Greene Geoffrey , Melanson Kathleen
Published: November 2023

Overweight and obesity remain prevalent worldwide, with millions of adults seeking to lose weight and improve health. Wearable technology can provide self‐monitoring and feedback, which have been shown to be beneficial in weight loss and maintenance. The Bite Counter® can be worn like a watch and has been validated in previous studies to be an effective tool in counting the number of bites taken by the user. Data analysis of this novel device requires the application of normative value parameters, previously established by creators of the device. However, these parameters have not been independently tested in real‐world situations. Data were analyzed from a pilot study in which 19 overweight and obese college‐aged adults consented (19.7 ± 1.6 years; 15 female & 4 male; BMI 29.0 ± 3.4 kg/m2), and 17 subjects completed, a one‐week intervention testing the efficacy of the Bite Counter® in establishing a personal bite count goal and reducing daily bite count. Days in which subjects used the Bite Counter® in their own free‐living environment, with no supervision, were analyzed. Eating occasions with fewer than 4 bites, and those that lasted 3600 seconds (automatic shut off time of device), were removed; additionally, raw data were transformed to z scores, and scores greater than 3.29 were removed to exclude outliers and reduce within‐subject variability. Raw and revised data were compared using paired t tests. The 19 enrolled subjects averaged 4.84 ± 2.43 days of device use, with two subjects not using it at all; device usage increased to 5.41 ± 1.84 days when excluding the two non‐users. Significant differences were found between average daily eating time in minutes (28.65 ± 12.84 vs. 21.36 ± 12.40, p=.007), average daily bite count (65.65 ± 31.03 vs. 61.48 ± 30.88, p=.004), and eating rate as measured by bites per minute (2.44 ± .92 vs. 3.15 ± .84, p=.038). However, average meal duration in minutes did not differ (8.06 ± 5.46 vs. 7.50 ± 4.58, p=.542). These results demonstrate that the application of normative value parameters lead to significant differences in most Bite Counter® outcomes, and may help future researchers more effectively interpret data from bite‐counting wearable technology.

Support or Funding Information

Funding: The University of Rhode Island Council for Research Grant, July 2015.
Effect of the sleep‐promoting by Polygonatum sibiricum rhizome extracts in vertebrate models
Authors: Jo Kyungae , Kim Hae Dun , Kim Singeun , Han Sung Hee , Choi Hyeon‐Son , Suh Hyung Joo
Published: November 2023

The sleep promoting effects of the water extract of Polygonatum sibiricum rhizome (PSE) were investigated in vertebrate model, by examining sleep quantity and quality. The content of GABA and tryptophan in PSE was calculated by HPLC system. Effect of PSE on pentobarbital‐induced sleep test in mice were applied to investigate sleep latency and duration. The total sleeping time and quality were determined using electroencephalogram (EEG) analysis of PSE and PSE with caffeine treated rats. Gene expression related to GABAA‐R2, GABAB‐R1 receptor, and serotonin receptor (Htr1a) receptors in rat brain were analyzed by real time PCR. As a result PSE was contained GABA (0.74 ± 0.01 mg/g extract solid) and tryptophan (0.12 ± 0.03 mg/g extract solid) that might be major contribution on the sleep activities of PSE. PSE at 160 mg/kg significantly regulated the sleep latency and duration (p < 0.001) in pentobarbital‐treated mice. Moreover, total sleeping time and sleep quality significantly increased with 160 mg/kg administration (p < 0.01), and also caffeine‐induced model represent the similarly result (p < 0.05). Especially the long‐term administration significantly increased the non‐REM and that decreased the REM (p < 0.01). However, the transcript level of GABAA‐R2, GABAB‐R1 receptor, and serotonin receptor (Htr1a) mRNA were unchanged in PSE treated rat brain. These results confirmed that PSE possessed the sleep‐promoting effect in vertebrate model and that its GABA and tryptophan can elicit the same kind of pharmacological effects on the central nervous system (CNS).
Identification of Phytochemicals in Muscadine Pomace and Their Anti‐inflammatory Activities on RAW 264.7 Murine Macrophages
Authors: Zhao Bo , Gu Liwei
Published: November 2023

Southern muscadine grapes are known to contain a variety of health‐promoting polyphenolic compounds. About 98% of these nutraceutical compounds in muscadine grapes are found in the skins and seeds. They are often discarded in the form of pomace after winemaking. The objective this study was to identify phytochemicals in muscadine pomace and determine their anti‐inflammatory activities. Muscadine wine pomace of three cultivars (Noble, Welder, and Carlos) was separated into skin and seeds. Part of the seeds was processed on a single‐screw press at 90°C to obtain seed oil and partially defatted seeds. This step reduced the fat content in seeds from about 13% to 5% (w/w). All samples were ground into powders and extracted using methanol/water/acetic acid (85:15:0.5; v/v/v). The resultant crude extracts were subject to acid hydrolysis and water/ethyl acetate partition. HPLC‐MS analyses showed that the major compounds in seeds and skins were ellagic acid, epicatechin and gallic acid. Welder seed extract contains the highest amount of ellagic acid (230 μg/mg extract), epicatechin (122 μg/mg extract) and gallic acid (107 μg/mg extract). RAW 264.7 macrophages were pretreated with extracts and stimulated with lipopolysaccharides to induce inflammatory responses. RT‐PCR results show that IL‐1 and IL‐6 gene expression were reduced by muscadine extracts while TNF‐α expression remained the same or slightly increased. Overall, the grape pomace contained several types of polyphenols and showed anti‐inflammation activities in vitro.

Support or Funding Information

This research is supported in part by Florida Viticulture Council and Florida Specialty Crop Block Grant
Analysis of Serum Ferritin and High Sensitive C Reactive Protein in Patients with Gout
Authors: Ma Aiguo , Wei Jingyan , Zhang Huaqi , Wu Dayong
Published: November 2023

Objective

The relationship between serum concentrations of ferritin and high sensitive C reactive protein in men and the risk of gout was unclear.

Methods

In this study we enrolled 600 male patients diagnosed with gout, 600 male patients with hyperuricemia, and 600 male health people as the control. The information of physical examination and related indicators was collected in all three groups, including height, weight, serum ferritin (SF), high sensitive C reactive protein (hs‐CRP), uric acid (UA), fasting blood glucose (FPG), triglyceride (TG), and total cholesterol (TC).

Results

The average concentration of serum ferritin (SF) was higher in gout group (135.27 μg/L) than in hyperuricemia group (114.45μg/L, p<0.05), and the control group (76.02 μg/L, p<0.05); the mean level of hs‐CRP in gout patients was 0.3 mg/dl, significantly higher than that in hyperuricemia group (0.13mg/dl) and the control group (0.09mg/dl) (all P<0.05). After adjusting for age, BMI, TG, TC, FPG and other confounding factors, SF levels were positively correlated with hs‐CRP levels in hyperuricemia group and gout group, while there was no association between SF and hs‐CRP levels in the control group. The multivariate logistic regression analysis showed that after adjusting for BMI, TG, TC, FPG, UA and other confounding factors, the high levels of SF (≥155.78ug/l) significantly increased risk of gout, with OR of 2.678 (95%CI, 1.484–4.833); higher levels of hs‐CRP (>0.9mg/dl) was also a risk factor of gout, with OR of 3.104 (95%CI, 1.727–5.580).

Conclusion

Serum concentrations of ferritin level and high sensitive C reactive protein were significantly elevated in patients with gout. These results suggest that hs‐CRP, and SF may be involved in the pathogenesis of gout; however, whether it can be used as a predictor of gout attack needs further study.

Support or Funding Information

The National Natural Science Fund (No. 81373000)