bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gut Microbiota Restores Central Neuropeptide Deficits Present in Germ Free Animals
Authors: Covasa Mihai , Duca Frank A , Swartz Timothy D 
Published: November 2023

Recent work has shown that gut microbiota plays an important role in host energy homeostasis. Indeed, germ‐free (GF) mice have lower levels of adiposity and leptin levels compared to conventionalized mice. Additionally, GF mice are resistant to obesity when placed on a high‐fat diet. Studies show that gut microbiota contributes to obesity by increasing energy extraction, promoting inflammation, and altering lipogenic and adipogenic enzymes. Moreover, recent work demonstrates the ability of the microbiota to alter expression and release of gut peptides that control appetite and regulate energy homeostasis. However, little is known about the neuronal response of these hormones in GF animals, especially leptin, which is strikingly decreased in these animals. Therefore, we aimed to determine the sensitivity of leptin in GF mice compared to conventional mice by injecting leptin and measuring levels of leptin receptor activation via STAT3 and PI3K pathways in the hypothalamus and hindbrain. We also measured expression of orexigenic and anorexigenic peptides in the hypothalamus and hindbrain to examine whether gut microbiota impacts central nervous system regulation of energy homeostasis. We found that GF mice had a significant increase in hypothyalamic NPY and AgRP mRNA expression and a decrease in hindbrain NPY and AgRP mRNA. mRNA expression of POMC and CART remained unchanged. Protein expression of hypothalamic STAT3 and pERK/ERK increased significantly in response to peripheral leptin. Further, administration of leptin normalized circulating levels of leptin, GLP‐1, PYY and ghrelin, all of which were significantly decreased in GF mice. Conventionalization of GF mice (10 days) restored the deficits in hypothalamic and hindbrain neuropeptides present in GF animals. These results show that gut microbiota regulates hypothalamic and hindbrain orexigenic/anorexigenic neuropeptide expression. This is in line with the role of gut microbiota in lipid metabolism and fat deposition that may contribute to excess fat in conventionalized animals under high feeding condition.Support or Funding InformationRomanian National Program PN‐II‐ID‐PCE‐2012‐4‐0608 no. 48/02.09.2013, “Analysis of novel risk factors influencing control of food intake and regulation of body weight”
Effects of Alcohol Consumption in Prevention of Colon Cancer in Rats
Authors: Klarich DawnKylee S , Penprase Jerrold , Cintora Patricia , Medrano Octavio , Erwin Danielle , Brasser Susan M , Hong Mee Young 
Published: November 2023

Alcohol consumption is a risk factor associated with colorectal cancer (CRC); however, some studies have reported that moderate alcohol may not contribute additional risk for developing CRC while others suggest that moderate alcohol provides a protective effect that reduces CRC risk. The purpose of this study was to determine the effects of moderate alcohol (20% ethanol) administered on alternate days for 3 months in male Wistar rats on biomarkers that were associated with CRC development. Blood samples and colon mucosa samples were collected from the experimental alcohol and the control groups (n = 12/group) at the end of the study and were used to evaluate a variety of biomarkers that were associated with inflammation, DNA damage, antioxidant activity, and acetaldehyde clearance. Blood alcohol content, liver function enzyme activities, and 8‐oxo‐deoxyguanosine (8‐oxo‐dG) DNA adducts were also assessed in serum. Rats treated with moderate alcohol were found to have significantly lower 8‐oxo‐dG levels in blood, a marker of DNA damage, with no significant increase in repair activity by colonic 8‐oxoguanine DNA glycosylase 1 (OGG‐1), a base excision repair enzyme responsible for removing 8‐oxo‐dG damage. The blood alcohol content and liver enzyme tests were not significantly different between groups, with the exceptions of alanine aminotransferase and lactate dehydrogenase, which were both significantly lower in the alcohol group. Moderate alcohol significantly decreased cyclooxygenease‐2 gene expression, a marker for inflammation that is associated with CRC risk. The alcohol group had significantly increased glutathione‐S‐transferase M1 (GSTM1) expression, which is an antioxidant defense enzyme that helps detoxify carcinogens, like acetaldehyde, and also resulted in significantly increased aldehyde dehydrogenase 2 (ALDH2) expression, which allowed for greater acetaldehyde clearance. Increased expression of GSTM1 and ALDH2 likely contributed to reduce mucosal damage that is caused by acetaldehyde accumulation. Additionally, by assessing the correlations within the alcohol group we did find a positive relationship between increased alcohol intake and increased OGG‐1 and ALDH2 gene expression. Other positive correlations were found that provided evidence that increased 8‐oxo‐dG level was positively correlated with liver function enzyme activities and gene expression of RelA, OGG‐1 repair enzyme, and GSTM1 detoxification enzyme. These results suggest that moderate alcohol does not increase CRC risk and may provide beneficial effects that reduce CRC risk, which was evidenced by reduced inflammation activity and lower DNA damage after alcohol exposure.Support or Funding InformationThis study was funded by NIH AA023291. Additional funds were received from the Kasch‐Boyer Endowed Scholarship in Exercise and Nutritional Sciences.
Nutritional Intervention Improves the Total Energy Intake in Cancer Patients
Authors: Hung Shy‐Fen , Wen Cheng‐Fan , Li Pei‐Rong 
Published: November 2023

Background20% causes of death in cancer patients were malnutrition rather than the tumor itself. Cancer patients during the treatment period often occurs gastrointestinal symptoms, including nausea, vomiting, oral mucosal damage, altered taste. These problems would affect the enteral nutrition, further exacerbated malnutrition, reduced immunity and prolonged the hospital stay. The previous study showed that weight loss would shorten survival of cancer patients. Another study showed death usually occurs when there is 30% weight loss. The effectiveness of short‐term nutrition intervention in hospitalized cancer patients might be prolonged survival.ObjectivesThe purpose of present study was to evaluate the effectiveness of nutritional intervention for hospitalized cancer patients. To evaluate the relationship between three‐year survival rate of cancer patients and the effectiveness of nutritional intervention by survival analysis.MethodsThis was a retrospectively observational study. The medical records of cancer patients receiving nutrition intervention during hospitalization were reviewed (n=291). Patients’ anthropometric measurements and blood biochemical parameters were recorded at the first, second and third nutritional intervention within a single hospitalization. The patients were further tracked three‐year survival (n = 214), and carried out the relevant factors of survival analysis.ResultsTotal Patients’ energy intake and percentage of TER (Percentage of Total Energy Requirement) were significantly increased after nutritional intervention (both p = 0.000). There were no significant differences in BMI (Body Mass Index) and blood biochemical parameters related nutrition during hospitalization. The survival analysis in be tracked three‐year survival patients was performed. Those patients’ percentage of TER were significantly increased after nutritional intervention, it was the same with all patient. Patients’ percentage of TER at third nutrition intervention higher, patients’ survival rate better (p=0.026).ConclusionsThe cancer patients’ total energy intake could be improved by nutritional intervention; it might be helpful to survival.
L‐Cysteine Supplementation Increases Adiponectin Synthesis and Secretion, GLUT4 and Glucose Utilization by upregulating Disulfide Bond A‐Like Protein Mediated by MCP‐1 and TNF‐α Inhibition in 3T3‐L1 Adipocytes Exposed to High Glucose
Authors: Achari Arunkumar E , Jain Sushil K 
Published: November 2023

Adiponectin is an anti‐diabetic and anti‐atherogenic adipokine; its plasma levels are decreased in obesity, insulin resistance, and type 2 diabetes. An adiponectin‐interacting protein named disulfide bond A‐like protein (DsbA‐L) play an important role in the assembly of adiponectin This study examined the hypothesis that L‐cysteine (LC) regulates glucose homeostasis through the DsbA‐L upregulation and synthesis and secretion of adiponectin in diabetes. 3T3L1 adipocytes were treated with LC (250 and 500 μM, 2 h) and high glucose (HG, 25 mM, 20 h). Results (n=3) showed that LC supplementation significantly (p < 0.05) upregulated the DsbA‐L, adiponectin and GLUT‐4 protein expression and glucose utilization in HG treated adipocytes. LC treatment along with insulin enhanced glucose utilization compared to either insulin or LC alone in HG treated cells (n=2). LC supplementation significantly (p < 0.05) promoted the secretion of total and HMW adiponectin secretion in HG‐treated adipocytes (n=5). In addition, LC significantly (p < 0.05) decreased ROS production and MCP‐1 and TNF‐α secretion in HG treated cells (n=3). We further investigated whether MCP‐1 and TNF‐α has any role of LC on DsbA‐L expression and adiponectin levels in 3T3‐L1 cells. Treatment with LC prevented the decrease in DsbAL (n=4) adiponectin (n=3) and GLUT‐4 (n=3) expression in 3T3L1 adipocyte cells exposed to MCP‐1 and TNF‐α. Thus, this study demonstrates that DsbA‐L and adiponectin upregulation mediates the beneficial effects of LC on glucose utilization by inhibiting MCP‐1 and TNF‐α secretion in adipocytes and provides a novel mechanism by which LC supplementation can improve insulin sensitivity in diabetes.Support or Funding InformationThe authors are supported by grants from the National Institutes of Health RO1 AT007442 and Malcolm Feist Endowed Chair in Diabetes
Impact of 15kDa Selenoprotein and Dietary Selenium on Initiation and Promotion in Colorectal Carcinogenesis
Authors: Tsuji Petra A , Canter Jessica A , Carlson Bradley A , Margulies Derek , Patterson Angelica , Gladyshev Vadim N , Yu Yunkai , Cao Liang , Davis Cindy D , Hatfield Dolph L 
Published: November 2023

The micronutrient selenium (Se) largely exerts its biological effects through incorporation into selenoproteins. Several selenoproteins, including the 15kDa selenoprotein (Sep15), are thought to play roles in both cancer prevention and promotion. Previously, Sep15 knockout (KO) mice were shown to be resistant to formation of chemically‐induced pre‐neoplastic lesions. In our current study, Sep15 KO mice and littermate controls were maintained on deficient (0.02 ppm) or adequate (0.1 ppm) dietary Se. Mice were injected with azoxymethane (AOM) or saline, followed by treatment with dextran sulfate sodium (DSS) or water, to initiate and promote colon tumorigenesis. Formation of pre‐neoplastic lesions was again dramatically reduced in Sep15 KO mice compared to littermate controls, independent of dietary Se levels. Fewer Sep15KO mice developed tumors when Se‐deficient, but formed a similar number of tumors as controls when Se‐replete. Tumor mass itself appeared to be similar in control and Sep15KO mice when Se‐deficient, and slightly larger in Sep15 KO mice when Se‐replete. This suggests that Sep15 KO mice may be protected against AOM‐induced cancer initiation, but not against AOM/DSS‐induced tumor formation, and that dietary Se may modify the outcome. To assess cancer initiation, hepatic mRNA expression of CYP2E1, the enzyme responsible for activating AOM to its mutagenic form, was quantitated, and found to be significantly reduced in untreated Sep15 KO mice compared to littermate controls in Se‐deficient conditions, whereas no differences were detected in AOM/DSS‐treated mice. Interestingly, there also appear to be Se‐mediated differences in hepatic CYP2E1 expression. Inflammation is a strong tumor promoter in colorectal cancer, and pro‐inflammatory serum cytokines were generally higher in mice treated with AOM/DSS compared to those injected with saline. Interestingly, serum interferon‐γ, TNFα and Cxcl1 levels did not differ between Sep15 KO mice and controls, regardless of dietary Se or inflammation treatment. Other cytokines are currently being assessed in serum, colorectal epithelia, and spleens.Support or Funding InformationNCI Intramural support; NIH CA080946 (VNG); Office of Dietary Supplements; Towson University Jess & Mildred Fisher Endowed Chair (PAT)
The AHR Pathway And Its Potential Role In The Regulation Of The 15 kDa Selenoprotein
Authors: Galinn Sarah E , Rosso Lauren E , Carlson Bradley A , Tobe Ryuta , Naranjo‐Suarez Salvador , Tsuji Petra A 
Published: November 2023

Several selenoproteins, including the 15kDa selenoprotein (Sep15), are thought to have roles in both cancer prevention and promotion. Sep15 belongs to the group of stress‐related selenoproteins, and though its functional role continues to be elucidated, this oxidoreductase resides in the ER and is thought to be involved in reduction or isomerization of disulfide bonds. Little is known about factors regulating Sep15 expression. Our preliminary analyses indicated that some dietary polyphenols decreased Sep15 mRNA expression in human colon cancer HT29 cells. Because many of these flavonoids are known to affect Arylhydrocarbon Receptor (AHR) and/or NRF2‐regulatory pathways, expression of AHR and NRF2‐related genes are being investigated in Sep15‐deficient and ‐sufficient HT29 colon cancer cells to elucidate the potential regulatory mechanisms of Sep15. Analysis of previously published microarray data indicated that mRNA expression of AHR‐pathway‐related genes was significantly changed in HT29 cells lacking Sep15 compared to controls, including the AHR‐nuclear transporter, the AHR‐interacting protein, and heat‐shock protein 90. Comparison of the NCI‐60 cell lines through CellMiner analysis revealed that mRNA expression of Sep15 and AhR was negatively correlated (p<0.05). Furthermore, treatment of HT29 cells with the NRF2‐agonist, sulforaphane, did not increase Sep15 mRNA expression. Thus, in the current study, HT 29 control and shSep15 cells were exposed to 2,3,7,8‐Tetrachlorodibenzo‐p‐dioxin (TCDD) or 5,6‐beta‐naphthoflavone to induce or inhibit the AHR‐signaling pathway. Gene expression is currently being assessed using qPCR and Western blotting. Preliminary analyses show that mRNA expression of TCCD‐induced CYP1A1 and CYP1B1 is significantly lower in Sep15‐deficient cells compared to controls. Independent of TCDD treatment, shSep15 cells also expressed a lower CYP1A2 mRNA expression than the control cells. Nuclear and cytosolic protein expression is currently being assessed. Preliminary results suggest that Sep15 may influence or be regulated by AhR‐dependent pathways, which may be important in regulation of colon carcinogenesis.Support or Funding InformationNational Cancer Institute Intramural support; Towson University Jess & Mildred Fisher Endowed Chair and a Faculty Development & Research Committee grant (PAT).
The association of vitamin D level with dietary Se intake in elderly Korean: based on the 2008–2011 Korean National Health and Nutrition Examination Survey
Authors: Lee Okhee , Yang YoonKyoung , Shin Juyoung 
Published: November 2023

The essentiality of vitamin D and Se in human nutrition have been well known. Their deficiencies in elderly were commonly suggested to increase the risks of cardiovascular disease, osteoporosis, dementia, sarcopenias etc. The dietary Se intake depends on the Se content of consumed foods and dietary pattern of a population. The food Se contents depend on Se status in soil, so they show wide variation even in the same food item. Due to its volatile nature, Se is difficult to analyze and needs specific caution when instrumentally chemical digestive analysis method is used. Therefore, the suitable database of Se for Korean foods is rarely observed. In this study, we analyzed the association of blood 25(OH) vitamin D level of 2008–2011 KNHANES datasets with dietary Se intake calculated using the food Se contents analyzed by INAA method. INAA is non‐destructive method which is no digestive method. The elderly with age over 60 year and participated in all the measurements of DXA, nutrition survey, and blood analysis were chosen. The dietary intake measured by 24‐hour recall method from nutrition dataset were used to calculate the selenium intakes of elderly. The food Se contents were coded using the KNHANES food database and used to calculate the dietary intake of elderly participated in KNHANES survey. The statistical analysis was conducted using SAS program (ver. 9.4) and considering the complex clustered sampling. The age‐standardized prevalence of Se intake deficiency in elderly Koreans over age 60y have a range from 39% to 63%, depending on age and gender. The lowest Se ingestions were found in both gender of elderly who have the age‐adjusted and unadjusted 25(OH) vitamin D level under 10ng/ml (p<0.001). In conclusion, this study suggested that blood 25(OH) vitamin D level is associated with dietary Se intake in aged Korean.Support or Funding InformationAcknowledgement: This work was supported by the National Research Foundation through Basic Study Support Program 2014(NRF‐2014‐0023314, NRF‐2013‐0023314, NRF‐2012‐0023314, NRF‐2010‐0023314) and Nuclear Research and Development Program (NRF‐2009‐0078272).
The prevalence of deficient Se intake in elderly Korean

Age group
β
SE(β)
t Value
Pr > |t|

60=<age<70
0.393
0.012
31.8
<.0001

70=<age<80
0.573
0.016
36.81
<.0001

80=<age
0.628
0.034
18.57
<.0001
Characterization of Cystathionine Beta‐Synthase and Cystathionine Gamma‐Lyase in the Production of Hydrogen Sulfide Biomarkers, Lanthionine and Homolanthionine, in a HepG2 Cell Culture Model
Authors: DeRatt Barbara , Ralat Maria , Gregory Jess 
Published: November 2023

Hydrogen sulfide (H2S) is an essential gasotransmitter with the ability induce vasodilation and exert other cardioprotective effects in‐vivo, yet accurate quantification of H2S is difficult and often erroneous. Proposed biomarkers, lanthionine and homolanthionine, are produced concurrently with H2S by the pyridoxal 5′‐phosphate (PLP) dependent‐transsulfuration enzymes, cystathionine beta‐synthase (CBS) and cystathionine gamma‐lyase (CSE). This study sought to determine the contribution of CBS and CSE in the production of H2S biomarkers in a HepG2 cell culture model. Isotopic tracers, [U‐13C5] L‐methionine and (3, 3 D2) L‐cysteine, were used to determine metabolic fluxes through the transsulfuration pathway before and after the inhibition of CSE by 1mM propargylglycine (PAG), a CSE specific inhibitor. Cellular methionine concentrations and remethylation kinetics were not affected by PAG addition, nor was extracellular cysteine pool size. CSE inhibition caused intracellular cystathionine to accumulate (P=0.012). We evaluated the CBS‐catalyzed appearance of [D2]‐cystathionine and [13C4]‐cystathionine from homocysteine condensation with cysteine or serine, respectively. The labeling pattern of cellular cystathionine showed that only 4% of the cystathionine pool was derived from the CBS‐catalyzed condensation of homocysteine with cysteine. Lanthionine concentrations were four times greater in cells with PAG compared to control cells (P<0.001) but enrichments were not affected by PAG addition. This suggests CSE does not contribute to lanthionine synthesis but CSE may catalyze some lanthionine cleavage. Homolanthionine production in control cells greatly exceeded that observed in PAG‐treated cells (P<0.001), which confirmed that CSE is essential in homolanthionine synthesis. These results support our primary human hepatocyte studies which showed that CSE is the primary source of homolanthionine production while CBS is solely responsible for lanthionine production. These data illustrate how this HepG2 model is useful for mechanistic investigation of H2S production.Support or Funding InformationSupported by NIH DK072398.
Comparison of Oral Iron Supplement Formulations for Normalization of Iron Status Following Roux‐en‐Y Bariatric Surgery
Authors: Mischler Renee , Armah Seth , Rosen Arthur , Choi Jennifer , Gletsu‐Miller Nana 
Published: November 2023

BackgroundIron deficiency is common after gastric bypass (GB) and treatment with oral supplementation using non‐heme iron, although currently recommended, is controversial. The study objective is to compare the effectiveness of oral iron supplementation using non‐heme versus heme iron for repletion of iron deficiency.MethodsUsing a randomized, controlled, single‐blind study design, women who had GB and were iron deficient received non‐heme iron (FeSO4, 65 mg t.i.d.) or heme iron (12 mg t.i.d.). Measures of iron status, including blood concentrations of ferritin, total iron binding capacity (TIBC), soluble transferrin receptor (sTfR), and hemoglobin were determined at baseline and at 2, 4, and 8 weeks after supplementation. Data is presented as mean ± SE, or mean (95% CI).ResultsThe study is ongoing, but preliminary findings are presented herein. Baseline characteristics of screened patients (N=28) are age: 40.4±1.4 years; BMI: 34±1.4 kg/m2; time since surgery: 5.7±0.6 years; ferritin: 38.0 μg/L (16.1, 59.9); TIBC: 379 μg/dL (352, 405); sTfR: 2368.1 μg/L (1583.6, 3152.7); hemoglobin: 12.1 g/dL (11.5, 12.6). Of screened patients, 57.1% were classified as iron deficient and 35.7% had anemia. To date, 8 iron deficient patients have completed the 8‐week study (4 per group). Of those who received non‐heme iron supplementation, an improvement in blood concentrations of hemoglobin (p= 0.01), TIBC (p< 0.001), and sTfR (p= 0.049) was seen; ferritin tended to improve (p= 0.068). Of those who received heme iron supplementation, no change in iron status was seen in any of the iron status biomarkers.ConclusionEarly data demonstrate that non‐heme iron supplementation appears to be effective for repletion of iron status. Findings may guide treatment of iron deficiency, which is very common following bariatric surgery.Support or Funding InformationInternational Copper Association USDA, ARP Assistantship, to RAM