bluuebunny/crossref_metadata_2025_split huggingface dataset:
In vivo Assessment of Lutein Absorption in Infant Formula using Mono‐diglycerides (MDG) Based Emulsification Technology
Authors: Vurma Mustafa , DeMichele Stephen , Lee Dana , Tso Patrick 
Published: November 2023

Previously we showed using the lymph fistula rat model that specific mixtures of MDG improved lymphatic lutein absorption by solubilizing lutein and facilitating gastrointestinal micelle formation compared to lutein suspended in triglyceride oils. The primary objective of this study was to determine manufacturing/formulation options to incorporate MDG and lutein into infant formula to retain the observed lutein absorption benefits. We compared using a conscious lymph fistula rat model, the intestinal uptake and lymphatic transport of lutein from five different liquid infant formula prototypes. Five groups of male adult Sprague Dawley rats (n= 4–7/group) were randomized to gastrically receive (~6.0 μg lutein per animal) one of the following infant formula prototypes containing ~2 mg/L lutein: (AET‐Control) lutein is premixed with safflower oil and then added to the oil phase; (AET‐1) lutein premixed with MDG and lecithin, and then added the oil phase; (AET‐2) lutein is premixed with MDG, and then added to the water phase; (AET‐3) lutein is premixed with MDG, and then added to the oil phase; and (AET‐4) lutein is premixed with MDG and choline chloride, and then added to water phase. Aliquots of lymph were taken at fasting and hourly for 8 hours for lutein and fatty acid analyses. Lutein premixed with MDG and added to oil phase directly (AET‐3) during processing did not improve lutein absorption as compared with AET‐Control. On the other hand, gastric delivery of AET‐1, AET‐2, and AET‐4 significantly improved lymphatic lutein output 2–8 hours after formula feeding versus AET‐Control. The percent increases in lutein absorption over the 8 hour period were the following: AET‐1; 142%; p<0.05, AET‐2; 121%; p<0.05, and AET‐4; 165%; p<0.05. In addition, there were significant increases in lymphatic fatty acid (docosahexaenoic, arachidonic, palmitic) outputs during the study period for formulas AET‐1 and AET‐2 as compared with AET‐Control. These data show that when lutein is premixed with MDG and lecithin (AET‐1) and added to the oil phase or lutein premixed with MDG (AET‐2) and choline (AET‐4) and added to the water phase, preserved the lutein absorption benefits previously observed with MDG ingredient research. MDG based emulsification technology has the potential to improve the absorption of lutein in infants.Support or Funding InformationDK059630, Abbott Nutrition ZA78
Acute Bioavailability of (Poly)phenolic Content of Different Varieties of Vaccinium spp. in Ovariectomized Rats
Authors: Maiz Maria , Cladis Dennis P. , Lachcik Pamela J. , Janle Elsa M. , Lila Mary Ann , Ferruzzi Mario G. , Weaver Connie M. 
Published: November 2023

Blueberries have a wide range of health promoting activities due to their high levels of (poly)phenols, including anthocyanins, flavonols, and phenolic acids. However, there are 1200 varieties of blueberries and their phenolic content varies greatly. Thus, the goal of this investigation was to characterize the total phenolic content in 9 varieties of Vaccinium spp. berries as well as determine whether there is a difference in their bioavailability after an acute dose in ovariectomized rats.Nine varieties of berries (Ira, Legacy, Montgomery, Onslow, SHF2B1‐21:3, Sampson, Cranberry, Bilberry and two Wild blueberry composites from the years 2012 and 2013) were selected based on PCA analysis of their anthocyanidin content and sourced from the North Carolina State University Blueberry Genome Repository. Berries were freeze‐dried and phenolics were extracted with 2% formic acid 80:20 MeOH:H2O solvent and purified using solid phase extraction (SPE). Total phenolic content was determined via the Folin‐Ciocalteu assay and individual phenolics where identified and quantified by HPLC‐MS.For the bioavailability study, eighty‐four Sprague‐Dawley rats were given an acute dose of 25mg of total phenolics/kg of body weight by gavage as a freeze‐dried blueberry powder solution (aq.) and serial blood draws and urine were collected over 8 hours. Plasma samples were extracted by SPE and analyzed by HPLC‐MS/MS for anthocyanin glycosides and flavonoid metabolites. Pharmacokinetic parameters (AUC, Cmax, and Tmax) were determined.Bilberry and Wild blueberry composite 2013 have a significantly higher total phenolic content than the other varieties, while Cranberry and Sampson were the least concentrated. Montgomery and Ira varieties had the highest bioavailability for Me‐Quercetin‐glc and Me‐Myricetin‐glc metabolites, respectively, by one‐way ANOVA (p < 0.05). The flavan‐3‐ols, catechin‐glucuronide (glc), epicatechin‐glc and their respective methylated metabolites, were not significantly different between varieties of blueberries.Total (poly)phenolic content and bioavailability of individual phenolics varied widely among blueberry varieties. This information will serve to inform future investigations in cells, animals, and clinical trials.Support or Funding InformationNational Center for Complimentary and Alternative Medicine
Resistant starch (RS) fermentation is prevented by low potency antibiotics (AB) neomycin and ampicillin
Authors: Guice Justin L , Carvajal‐Aldaz Diana G , Page Ryan C , Raggio Anne M , Martin Roy J , Husseneder Claudia , Durham Holiday A , Geaghan James P. , Pelkman Christine L , Marco Maria L , Janes Marlene , Coulon Diana , Keenan Michael J 
Published: November 2023

In a previous study we reduced bacterial genera that ferment RS with AB treatment then stopped AB prior to feeding RS. Subsequent fermentation of RS was good even without a transplant of microbiota from other rats fed RS and prior reduced bacterial genera increased (EB14). We now report use of the same AB (neomycin 0.5 g/L and ampicillin 1g/L in drinking water) at the same time as feeding RS. Sprague Dawley rats were assigned into one of four groups and fed ad libitum for four weeks. The groups included: 1. positive control (high RS, low fat diet [LF], no AB), 2. negative control (no RS, LF, no AB); 3. LF, high RS, AB; and 4. high fat (HF), high RS, AB. We measured effects of fermentation: pH of cecal contents, empty cecum weight (ECW), short‐chain fatty acids (SCFA), glucagon‐like peptide 1 (GLP‐1), RS in cecal contents, four bacterial genera known to be involved in fermentation of RS and total bacterial numbers. HF group 4 was included to see if AB might improve fermentation of RS compared to no AB because Cani et al. (2008) had reported that AB reduced endotoxemia in diet‐induced obesity. AB reduced Lactobacillus spp. and Bifidobacterium spp., but not Bacteroides spp. or total bacteria. Empty cecum weights of groups given AB and positive control were greater than the negative control. RS increased acetate and butyrate as well as decreased pH of cecal contents and increased empty cecum weights; AB treatment in both LF and HF prevented these effects (p<0.05). AB also had double the amount of GLP‐1 in serum and double the amount of RS in cecal contents compared to positive control, and negative control had minimal amounts of both GLP‐1 and RS. Thus, it appears that half of the RS was not fermented in the positive control and AB eliminated fermentation of RS when given at the same time as feeding of RS. However, increased ECW and GLP‐1 are a concern for future use of AB for reduction of fermentation of RS for mechanistic studies.Support or Funding InformationFunding: Ingredion Incorporated and LSU AgCenter.
Effects of curcumin metabolites on human colon adenocarcinoma cells
Authors: Cheng An‐Chin , Lee Ming‐Fen , Li Cheng‐Ta , Chang Kai‐Hsun , Pan Min‐Hsiung 
Published: November 2023

Stepwise cancer development involves metastatic migration as well as uncontrolled cell growth. Cancer cells undergo migration and invasion which allow them to translocate within tissues. Tetrahydrocurcumin (THC), a major metabolite of curcumin, exhibits anti‐carcinogenesis and antioxidation in vivo. In the present study, we found that THC and two other metabolites of curcumin, tetrahydrodemethoxycurcumin (THDC) and tetrahydrobisdemethoxycurcumin (THBC), could reduce the survival ratio of human colon adenocarcinoma cells, COLO205, HCT116, and HT29, in a dose‐dependent manner. The results also indicated that the fewer the methoxy groups of the curcumim metabolites, the more the inhibitory effects. However, curcumin metabolites did not trigger apoptotic cell death in COLO205 cells significantly, whereas curcumin did. Our data also strongly suggest a role of THBC in inhibiting cellular migration in HCT116 cells. Taken together, these results demonstrated the anticancer efficacy of curcumin metabolites which provides a potential application basis for the prevention of human colon cancer.Support or Funding InformationThis study was supported by NSC102‐2320‐B‐309‐001‐MY3 to M‐F Lee and NSC100‐2313‐B‐309‐003 to A‐C Cheng.
Omega‐3 fatty acid‐rich fish oil supplementation prevents rosiglitazone‐induced osteopenia in insulin resistant C57BL/6 mice
Authors: Rahman Md Mizanur , Halade Ganesh , Williams Paul 
Published: November 2023

Rosiglitazone (RSG) is a very effective insulin sensitizing and glucose‐lowering drug, however, associated with bone loss resulting in increased peripheral fractures. RSG‐induced bone loss occurs mainly due to increased bone resorption, and bone marrow adiposity. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)‐rich fish oil is known to attenuate both bone resorption and bone marrow adiposity. We hypothesize that co‐administration of EPA and DHA‐rich fish oil prevents RSG‐induced bone loss. In this report, we investigated the effect of co‐administration of fish oil on RSG‐induced bone loss in C57BL/6 mice and the mechanisms underlying this preventive effect. Twelve‐month‐old C57BL/6 female mice were fed iso‐caloric diet supplemented with corn oil (CO), fish oil (FO), RSG+CO and RSG+FO for 5 months. Bone mineral density (BMD) was analyzed by dual energy x‐ray absorptiometry (DXA). RSG treatment reduced BMD in both CO and FO groups. However, mice fed RSG+FO exhibited significantly higher levels of bone mineral density (BMD) in different bone regions as compared to CO alone or RSG+CO fed groups. Reduced activity of COX‐2, enhanced activity of alkaline phosphatase were observed in LPS treated bone marrow (BM) cells from RSG+FO treated mice as compared to RSG+CO group. LPS treated BM cells from RSG+FO treated mice also expressed lower levels of Cathepsin K and PPAR‐γ as compared to RSG+CO group. LPS‐stimulated BM and splenocytes from RSG+FO also produced significantly lower level of pro‐inflammatory cytokines, TNF‐alpha and IL‐6 and higher level of anti‐inflammatory cytokine, IL‐10 as compared to RSG+CO group. We further examined the effect of DHA and EPA with RSG on bone morphogenic protein‐2 (BMP‐2)‐induced osteogenesis and adipogenesis in C3H10T1/2 cells and RANKL‐induced osteoclastogenesis in RAW264.7 cells in‐vitro. DHA restored RSG‐induced reduction of osteoblast differentiation and RSG‐induced up‐regulation of adipocyte differentiation in C3H10T1/2 cells. DHA also inhibited RSG‐induced up‐regulation of osteoclast differentiation of RANKL treated RAW264.7 cells. In conclusion, we provide evidence that FO co‐administration with RSG may prevent RSG‐induced bone loss by inhibiting markers of inflammation, osteoclastogenesis and adipogenesis and by enhancing osteogenesis in bone microenvironment.Support or Funding InformationThis study was supported by NIH contract grant number AG034233 (M.R.)
Acetylcholine‐signaling inhibitors for lung cancer therapy
Authors: Dasgupta Piyali , Lau Jamie K , Brown Kathleen C , Rollyson William D , Stover Cody A , Rimoldi John M , Cutler Stephen J , Hardman W Elaine , Carpenter A Betts , Chen Yi C 
Published: November 2023

Cigarette smoking is a major risk factor for the development of small cell lung cancer (SCLC) and non‐small cell lung cancer (NSCLC). Nicotine is the addictive component of cigarette smoke. Nicotine (at concentrations present in the plasma of moderate smokers) accelerates the growth, angiogenesis and metastasis of lung cancers. The biological activity of nicotine is mediated by nicotinic acetylcholine receptors (nAChRs). The endogenous ligand for nAChRs in the lung is the neurotransmitter acetylcholine (ACh). ACh is known to be an autocrine growth factor for both SCLC and NSCLC. One of the ways that nicotine and cigarette smoke promote the growth of lung cancers is by promoting the production of ACh, which binds to its cognate receptor (on lung cancer cells) in an autocrine manner and induces the proliferation of lung cancer cells. The objective of the present study is to investigate the growth‐inhibitory activity of acetylcholine‐signaling pathway in SCLC and NSCLC. We show that three acetylcholine‐signaling inhibitors, BW813U, hemicholinium‐3 and vesamicol, cause robust apoptosis in human NSCLCs. The anti‐cancer activity of vesamicol was also confirmed in athymic mouse models. Although there are several targeted therapies against NSCLC, they do not provide optimum efficacy in NSCLC patients who are exposed to cigarette smoke. Our studies will facilitate the identification of targeted therapies for the population of lung cancer patients who are smokers.Support or Funding InformationFunding for our study was supported by an NIH R15‐AREA Grant (1R15HL113681‐01A1), ACTSI Grant from Marshall University, the Flight Attendant Medical Research Institute YCSA Grant (82115), and the West Virginia IDeA Network of Biomedical Research Excellence (P20RR016477 and P20GM103434).
Role of the transcription factor Yin Yang 1 in non‐small cell lung cancer
Authors: BOUCHERAT Olivier , CHABOT Sophie , BOURGEOIS Alice , PROVENCHER Steeve , PAULIN Roxane , MALTAIS François , BONNET Sébastien 
Published: November 2023

BackgroundLung cancer is the most prevalent cancer type worldwide by both diagnosis and mortality, with non‐small cell lung cancers (NSCLCs) featuring as the most common histological subtype, the latter of which consists of squamous (epidermoid), adenocarcinoma, and large cell carcinoma. Rates of lung cancer will continue to rise owing to high levels of cigarette consumption and aging populations. Despite increased surgical resection rates, optimization of chemo‐radiotherapy and the introduction of targeted therapies, the treatment outcome for NSCLC remains poor. Therefore, identification of new molecular targets, which are essential for proliferation of tumor cells, will benefit both treatment and chemoprevention of NSCLC. The Yin Yang 1 (YY1) transcription factor has a pivotal role in normal biological processes such as development, differentiation, replication and cell proliferation exerting its effects on a huge number of genes involved in these processes. Due to its functions during lung morphogenesis, we hypothesize that YY1 is overexpressed and contributes to the pro‐proliferative and anti‐apoptotic phenotype of cancerous cells.Method/ResultsExpression level of YY1 was first examined by immunohistochemistry (n=5) and western blot (n=11) in resected tumor tissue of NSCLC patients (stages I–III) and compared to adjacent non‐cancerous lung tissue. Results showed that YY1 expression is significantly increased in squamous cell carcinoma and adenocarcinoma of the lung. A greater proliferation rate (Ki67 labeling) was associated with strong YY1 expression in these human lung tumors. In vitro, transient transfection experiments with A549 lung adenocarcinoma cells showed that depletion of YY1 levels by short interfering RNA reduced proliferation (Ki67 labeling and MTT assay, p<0,001), resistance to apoptosis (Annexin V assay, cleaved caspase‐3 expression, p<0,05) and migration (wound healing assay, p<0,001). In addition, YY1 knockdown improved in vitro NSCLC sensitivity to Etoposide/Cisplatin, two chemotherapeutic agents.ConclusionTaken together, these findings suggest that up‐regulation of YY1 plays an important role in the development of lung cancer. Susceptibility of YY1‐depleted A549 cells and YY1 heterozygous mice to induce tumors is currently under investigation. Analysis of YY1 expression in a larger cohort of patients may reveal prognostic information and deserves further study.Support or Funding InformationNone
NLRP3 Inflammasome as a Novel Target for Docosahexaenoic Acid and Its Metabolites to Abrogate Glomerular Injury during Hyperhomocysteinemia
Authors: Chen Zhida , Conley Sabena M. , Li Guangbi , Xia Min , Gehr Todd W. , Boini Krishna M. , Li Pin‐Lan 
Published: November 2023

It has been reported that Ω‐3 fatty acid, docosahexaenoic acid (DHA) is a clinically significant therapeutic aimed at reducing inflammation and prevention of inflammatory injury in glomeruli associated with different diseases such as hypertension and diabetes mellitus. However, the mechanism by which DHA and its metabolite exert anti‐inflammatory actions remains unclear. The present study was designed to test whether the intracellular, NOD‐like receptor family, pyrin domain containing 3 (NLRP3) inflammasome may serve as a novel therapeutic target for treatment or prevention of glomerular injury in hyperhomocysteinemia (hHcys). To answer this question, Nlrp3 knockout (Nlrp3−/−) and wild type (Nlrp3+/+) mice were fed a folate‐free (FF) or normal diet (ND) for 4 weeks to induce hHcys. Our studies found that using this experimental model of hHcys doubled plasma Hcys levels in FF fed mice. Neither administration of DHA nor a lipoxygenase (LOX) inhibitor, cinnamyl‐3, 4‐dihy‐droxyl‐cyanocinnamate (CDC) had an effect on Hcys levels. Confocal microscopic analysis showed that the FF diet increased the colocalization of inflammasome protein NLRP3 with ASC or with caspase‐1, suggesting NLRP3 inflammasome formation during hHcys induced by the FF diet. DHA treatment almost completely blocked this formation of NLRP3 inflammasome in glomeruli. However, mice receiving both DHA and CDC, showed enhanced glomerular inflammasome formation during hHcys. By immunohistochemical staining, we revealed that treatment with DHA and CDC inhibited IL‐1β production in glomeruli of mice with hHcys. Furthermore, the urinary protein and albumin excretion as well as glomerular damage index were significantly lower in mice with hHcys receiving DHA alone, but not in mice treated with DHA and CDC. These results provide the first evidence that DHA and its lipoxygenase products may abrogate the activation of NLRP3 inflammasomes and thereby prevent glomerular injury or sclerosis induced by hHcys. The NLRP3 inflammasome in podocytes of glomeruli may be a potential new therapeutic target for treatment of chronic glomerular disease by DHA or its metabolites.Support or Funding InformationSupported by NIH grants DK054927,HL07356 & HL057244
The Effects of 4‐Methylumbelliferone (4‐MU) on Hyperglycemia in Type 2 Diabetic Mice
Authors: Edwards Jasmine Sheria , Sunkari Vivekananda , Bollyky Paul 
Published: November 2023

Hyperglycemia is the underlying condition in diabetes that is associated with increase in morbidity and mortality. There is a need for other and more cost‐effective treatments directed at regulating blood‐glucose levels. Hyaluronan (HA) is an extracellular matrix component linked to diabetes. Higher concentrations of HA are found in the pancreatic islets and serum of individuals with Type 2 Diabetes (T2D). Based on these findings we hypothesized that inhibition of HA synthesis can lead to improved glycemic control in Type II Diabetics. To determine the effects of HA inhibition in T2D, 4‐Methylumbelliferone (4‐MU) was used to treat diabetic mice. Diabetic mice fed 4‐MU rapidly (<48 hours) became normoglycemic and maintained glycemic control through the duration of the experiment. These animals demonstrated a significant decrease in blood‐glucose and a partial decrease in weight. Quantification of insulin by enzyme‐linked immunosorbent assay (ELISA) showed that both serum and islets cultures from 4‐MU treated mice exhibited increased insulin production. Consistent with this data, mice lacking CD44 (HA receptor) show higher levels of insulin production while islets from CD44−/− mice produce more insulin in response to glucose challenge ex vivo. This data indicates that HA is increased in T2D and negatively regulates insulin production in a CD44‐dependent manner. We propose that 4‐MU, the active ingredient in a drug called “hymecromone” that is currently approved to treat biliary spasm, could be repurposed to treat hyperglycemia in T2D.Support or Funding InformationThis work was supported in part by National Institutes of Health grants and a BIRT supplement. This work was also supported by grants from the Juvenile Diabetes Research Foundation and Larry L Hillblom foundation fellowship.
Weight Management in Primary Care Validated by Evidence Based Algorithm
Authors: Jacks Denise G , Einstein George P , Tulp Orien L 
Published: November 2023

To determine the efficacy of evidence based algorithms [EBA] applied to weight loss management in a primary setting, we examined four cross sectional correlational studies on weight loss and management in over 1,000 out‐patients. Patients encompassed a wide age spectrum [age 17 to 78 yrs], 70% females, Body Mass Index [BMI] 27–45 kg/m2. Patients with type II diabetes [NIDDM] were permitted if controlled with drugs or diet. Markers of metabolic syndrome [MS] including elevated blood pressure [BP], dyslipidemia [elevated triglycerides [TG], lowered HDL‐Cholesterol [HDL‐C], elevated fasting blood glucose [FBG], and central obesity [CO] were monitored for 52, 56, or 102 weeks using one of 4 separate drug or drug combinations [Lorcaserin, Phentermine/Topiramate, Naltrexone/Bupropion, Liraglutide]. Results indicated all groups lost weight [3.3 to 6.6 lbs] with corresponding decreases in waist circumference [−2.5 to 5.2 in], plasma TG [−4.8 to 13.3 mg/dl, Systolic [−0.7 to 2.8 mmHg.] and Diastolic BP [−0.8–7.9 mmHg] and FBG [−.0.8 to −7.9 mg/dl] with the greatest weight loss with the Phentermine/Topiramate combination after 52 to 102 weeks of observation. These results indicate that long term administration of weight loss medications can be a safe and effective regimen for weight control.Support or Funding InformationSupported by Institutional Resources of USAT and the Einstein Institute