bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pyrogallol, a microbial metabolites from mango tannins (Mangifera Indica L.) suppresses breast cancer ductal carcinoma in situ proliferation in both in vitro and in vivo
Authors: Mertens‐Talcott Susanne U , Kim Hyemee , Barnes Ryan , Talcott Stephen T , Nemec Matthew 
Published: November 2023

It is estimated that 1 in 10 newly diagnosed cancer cases will be female breast cancer, and therefore there is an ongoing need to research novel treatment options. Polyphenolics are secondary plant metabolites that have been shown to have anti‐cancer effects in multiple cancer models without the deleterious side effects of conventional small molecules. This research, focused on the anti‐proliferative activities of pyrogallol, an intestinal microbial metabolite of mango polyphenols. Mice were xenographed with MCF10DCIS.COM cells in order to determine the anti‐proliferative of pyrogallol on ductal carcinoma in situ breast cancer (DCIS). Treatment animals received either 0.2mg/day or 0.8mg/day pyrogallol, and both treatment groups had significantly decreased tumor volumes compared to the control animals after 4 weeks of treatment. Plasma and tumor tissue was assessed in order to determine in pyrogallol or its metabolites were present in circulation or at the site of action. Additionally, biomarkers along the AMPK‐mTOR signaling axis were affected at mRNA, protein and phosphorylated protein levels. These results suggest that anti‐proliferative activities of mango polyphenols may be mediated by pyrogallol as a central bioactive metabolite that is systemically absorbed. Findings indicate that a diet rich in gallotannins that are microbially metabolized to pyrogallol may prevent the advancement of DCIS breast cancer.Support or Funding InformationMango National Board
Comparing Gene Expression Between Resveratrol Sensitive and Insensitive Cells Using RNA‐Sequencing Methods
Authors: Cranney Caleb Webster , Kenealey Jason 
Published: November 2023

Cancer treatments, while steadily improving in quality and effectiveness, continue to depend primarily on compounds toxic to non‐cancerous cells. These treatments, while demonstrating effectiveness against specific strains of cancer, often lead to debilitating and degenerate human disease. Resveratrol, a naturally occurring polyphenol found in the skin and seeds of red grapes, has been demonstrated to have anti‐cancerous properties. While much research has been done the general chemotherapeutic effect of resveratrol, little has been determined about the precise mechanism through which resveratrol specifically targets cancerous cells. By studying these mechanisms, one could perhaps learn to mimic or enhance it's nontoxic chemotherapeutic qualities in cancer treatments. We analyzed gene expression data between cancer cells with and without resveratrol treatment (focusing on both coding and noncoding RNA) to pinpoint with greater accuracy the biochemical pathways involved in this unique chemotherapeutic. To examine this, RNA sequencing methods were performed on MDA‐MB‐231 breast cancer cells on samples with and without resveratrol treatment. We applied RNA sequencing methods in a similar manner to a strain of the same cell line that developed an insensitivity to resveratrol. This cell line was developed through incrementally increasing resveratrol concentrations in the media over 8 months. The data was run through a Gene Set Omic Analysis (GSOA) program developed by bioinformatics professors at BYU. We have identified pathways that are modulated in response to resveratrol that help elucidate the chemotherapeutic mechanism of resveratrol. Studying impacted biochemical pathways identified by the analysis can reveal nontoxic methods of cancer treatment.Support or Funding InformationSimmons Center for Cancer Research Undergraduate Research Fellowship, BYU Life Sciences Start‐up Grant
Carotenoid profile and antioxidant activity of tortillas elaborated from yellow creole maize (Zea mays L.) by conventional nixtamalization process
Authors: Mora‐Rochin Saraid , Bañuelos Ana Belinda Corrales , Serrano Diego Misael Angulo , Rodriguez Edith Oliva Cuevas , Moreno Cuauhtemoc Reyes , Milan‐Carrillo Jorge 
Published: November 2023

Maize (Zea mays L.) is a widely consumed cereal in Mexico and Central America, mainly in the form of tortillas. Creole maize grains have multiple colors provided by two large families of pigments: 1) phenolics and 2) carotenoids, which are the most abundant in maize. Carotenoids are subject to many chemical changes induced by different processing conditions used in the food industry. The main process at which maize is subject to prepare tortillas is nixtamalization. This process may generate lossess of bioactive compounds due to the thermal alkaline cooking, however, it's been shown that the remaining compounds have a better bioavailability. The objectives of the present study were to evaluate the effect of traditional nixtamalization process and the profile levels of carotenoids, total phenolic content, hydrophilic (ORACH, ABTS and DPPH) and lipophilic (ORACL) antioxidant activity on four different yellow (Y) creole maize (264, 317, 320 and 502), and processed into tortillas. The results showed a 50% decreased in the total phenolic content, and hydrophilic antioxidant activity (ORAC, ABTS and DPPH) when nixtamalized tortilla (NT) was analyzed. This could be related with the concentrations found in tortillas made from creole maizes, which are higher than those reported by other authors. Among the pigmented genotypes, NT made from Y‐502 maize showed the highest total phenolic content (147.7 mg GAE/100 g DM), and antioxidant activity using the ORACH (6,467 μmol TE/100 g DM), DPPH (1,385 μmol TE/100 g DM) and ABTS (4,250 μmol TE/100 g DM) methods. Additionally, the same genotype showed the highest concentration of total carotenoids and lipophilic antioxidant capacity (531.9 μg Lutein/100 g DM and 13,492 μmol TE/100 g DM). On the other hand, carotenoid profiles analysis showed 64% increased in Lutein when NT made from Y‐317 maize were used. However, when Lutein and Zeaxanthin were analyzed in raw grain and NT, higher concentrations of carotenoids were found. The present study demonstrated that nixtamalization of yellow creole maize from Sinaloa, not only retain bioactive compounds and has antioxidant capacity, but also increases the concentration of bioactive compounds.Support or Funding InformationPROFAPI‐UAS‐2014‐137 AND CONACYT CIENCIA BASICA (168279)
Efficacy of Chewing Gum as a Delivery System for Water and Fat Soluble Vitamins
Authors: Khoo Weslie Yu Heng , Lambert Joshua D 
Published: November 2023

Chewing gum is a popular product among consumers and chewing gums containing functional ingredients including botanical extracts and vitamins are commercially‐available. In the present study, we examined the release kinetics and plasma bioavailability of a panel of water‐soluble and fat‐soluble vitamins from two commercially available vitamin supplemented gums. We have recruited 15 healthy subjects (age: 22–52 yrs, 60% women) and employed a single‐blind, placebo‐controlled cross‐over study design. Time‐dependent changes in saliva and plasma levels of vitamins were determined by high‐performance liquid chromatography using both ultraviolet light and electrochemical detection methods. In general, the component water‐ and fat‐soluble vitamins in the gums were released from the matrix into the saliva, and the levels in the plasma were elevated compared to levels following the placebo. We found that the release of water‐soluble ascorbic acid, niacinamide, and pyroxidine from the gum into the saliva during chewing was 52.1–62.1%, 76.8–80.6% and 40.0–70.4% of its available content, respectively. The release of fat‐soluble dl‐alpha‐tocopheryl acetate into the saliva during chewing was 30.4–44.0% of the available content. Furthermore, there was a near‐complete release of fat‐soluble retinyl palmitate content from the gum into the saliva. Plasma ascorbic acid and niacinamide levels were increased by 78.8–82.8% and 215.1–273.4%, respectively, in vitamin‐supplemented chewing gums compared to baseline. Analysis of plasma retinol and dl‐alpha‐tocopherol are still ongoing. To the best of our knowledge, this is the first report of the efficacy of chewing gum to deliver vitamins to human subjects. Further studies in deficient subjects are needed to determine whether chronic use of vitamin‐supplemented chewing gum is an effective approach to correct deficiency.Support or Funding InformationVitaball Inc.
Enhanced Solution Concentration of Quercetin in Amorphous Solid Dispersions
Authors: Gilley Andrew , Arca Hale Cigdem , Nichols Brittany , Edgar Kevin , Neilson Andrew Peter 
Published: November 2023

The flavonol quercetin is present in foods such as apples and onions and has potential beneficial bioactivities against cardiovascular disease, obesity, and oxidative stress. However, the benefits of quercetin are limited by poor bioavailability, primarily attributed to its crystallinity (resulting in low aqueous solubility) and extensive Phase‐II/III metabolism. Increasing solution concentrations of quercetin in the intestinal lumen has the potential to increase its diffusion across the unstirred water layer, thus improving absorption. Improving the bioavailability of quercetin is critical for enhancing its efficacy in vivo. Various strategies have been employed to improve quercetin dissolution in the intestinal lumen. One promising approach is to incorporate quercetin into amorphous solid dispersions (ASD). Cellulosic polymers with carboxylic acid functionality disperse quercetin, eliminating crystallinity, and selectively release quercetin at intestinal pH due to electrostatic repulsion of deprotonated acid groups. We assessed the utility of commercially available and novel cellulose derivatives for improving in vitro dissolution properties of quercetin, measured by the area under the concentration/time curve (AUC). Quercetin was dispersed via spray drying with novel cellulose derivatives [cellulose acetate suberate (CASub) and cellulose acetate adipate propionate (CAAdP)], and commercially available derivatives [hydroxypropylmethyl cellulose (HPMCAS) and carboxycellulose acetate butyrate (CCAB)]. Amorphous structure was confirmed by X‐ray diffraction. In vitro dissolution was performed at gastric and small intestinal pH (1.2 and 6.8, respectively). Crystalline quercetin showed poor solubility at both gastric and intestinal pH. At pH 1.2, amorphous quercetin in all cellulose derivatives showed poor dissolution, as expected. At pH 6.8, 10% (w/w) amorphous quercetin in CCAB provided significantly enhanced quercetin solution concentrations compared to crystalline quercetin and 25% and 50% amorphous quercetin; thus, 10% quercetin was employed for the other polymers. Amorphous quercetin (10%) in HPMCAS provided enhanced dissolution profile for quercetin at intestinal pH, substantially increasing its AUC compared to quercetin dispersed in CCAB. These results provide promising, novel opportunities for increasing the bioavailability of quercetin in vivo, and support the use of HPMCAS to achieve this. Furthermore, in vivo bioactivity studies are warranted to assess the ability of ASD to improve upon the bioactivity of crystalline quercetin.Support or Funding InformationFunding provided by the Institute for Critical Technologies and Applied Science at Virginia Tech.
Inhibition of high glucose‐induced diabetic retinal angiogenesis by dietary compound chrysin
Authors: Kang MinGyeong , Kang Young‐Hee 
Published: November 2023

Diabetic retinopathy (DR) has been implicated in patients suffering from chronic diabetes mellitus as pathological complications, characterized by diabetic retinal edema and abnormal retinal blood vessel outgrowth leading to diabetic vision loss. Chrysin is a natural flavonoid found in herb and honeycomb and possesses various bioactive properties. This study investigated to determine protective effects of chrysin on retinal angiogenesis caused by diabetic episode. Human retinal microvascular endothelial cells were incubated in media containing 27.5 mM mannitol (+5.5 mM glucose) or 33 mM glucose for 2 d in the presence of non‐toxic chrysin at 1–20 μM. High glucose upregulated the induction of the angiogenic markers of hypoxia inducible factor (HIF)‐1α and vascular endothelial growth factor (VEGF). In contrast, chrysin attenuated the induction of these angiogenic marker proteins. In the in vivo animal model of db/db mice, oral administration of 10 mg/kg chrysin decreased the retinal induction of HIF‐1α and VEGF and blocked retinal edema in db/db mice. These result demonstrated that chrysin inhibited retinal angiogenesis and edema retinal by attenuating the induction of angiogenic factors under diabetic circumstances. Therefore, chrysin may be a therapeutic agent in antagonizing diabetic retinopathy.Support or Funding InformationThis study was supported by National Research Foundation of Korea (2015R1A2A2A01006666) and Brain Korea 21 plus program by Ministry of Education of Korea (22A20130012421).
Gossypetin suppresses acidification‐related protein expression and lysosomal enzymes secretion in RANKL‐mediated osteoclasts
Authors: Antika Lucia Dwi , Lee Eun‐Jung , Kang Young‐Hee 
Published: November 2023

The imbalance between osteoblastic bone formation and osteoclastic bone resorption in the bone marrow microenvironments leads to osteolytic bone diseases including osteoporosis. Osteoclast‐mediated bone resorption is accomplished by delivering proton (H+) and secreting lysosomal formation of cathepsin K into acidic resorption lacunae. Gossypetin, a flavonoid isolated from Hibiscus species has been shown to possess anti‐microbial and anti‐atherosclerotic activities. The current study investigated the anti‐osteoporotic effects of 1–20 μM gossypetin on suppressing bone resorption in 50 ng/ml receptor activator of nuclear factor κB‐ligand (RANKL)‐differentiated Raw 264.7 murine macrophages for 5 days. When gossypetin was supplemented to RANKL‐induced osteoclasts, the number of multinucleated osteoclasts was reduced and the area of the resorption pits was diminished in a dose‐dependent manner, evidenced by tartrate‐resistance acid phosphatase activity and bone resorption kit assay. Western blot and PCR analysis showed that 20 μM gossypetin abrogated the induction of carbonic anhydrase II, vacuolar‐type H+‐ATPase and chloride channel‐7, all responsible for the bone acidification. In addition, gossypetin suppressed organic matrix degradation of mature osteoclasts through down‐regulating lysosomal enzymes secretion containing cathepsin K and matrix metalloproteinase‐9, indicating the decreased bone resorption activity. These results demonstrated that gossypetin might be a potential agent targeting against osteoclastogenic resorption.Support or Funding InformationThis study was supported by Brain Korea 21 plus program by Ministry of Education of Korea (22A20130012421).
Astragalin attenuates allergic airway inflammation by modulating macrophage infiltration in asthmatic mice
Authors: Kim Yun‐Ho , Choi Yean Jung , Kang Young‐Hee 
Published: November 2023

Pulmonary fibrosis and destruction are likely to be the main contributors to pathophysiological lung dysfunction, which may be attributed to any subsequent development of emphysema. We recently reported that astragalin allayed oxidative stress‐associated pulmonary fibrosis through disturbing airway epithelial mesenchymal transition and epithelial autophagic stress. This study attempted to identify how airway inflammation and remodeling led to the failure of lung function and how astragalin affected airway and pulmonary remodeling in the progression of inflammatory lung diseases including asthma, emphysema and pulmonary fibrosis. We found that astragalin attenuated pro‐inflammatory responses through diminishing the MCP‐1 secretion and the ICAM‐1 expression in 20 μM H2O2‐exposed airway epithelial BEAS‐2B cells. Oral administration of astragalin suppressed the induction of MCP‐1, CD11b(+) and F4/80(+) in OVA‐sensitized mouse airways and lungs. Additionally, mast cells were infiltrated in the airway epithelium in OVA‐challenged mice, and such infiltration was blocked by supplementing 20 mg/kg astragalin in sensitized‐mice. Our results demonstrated that astragalin may ameliorate pulmonary inflammation and remodeling by suppressing the production of several inflammatory mediators.Support or Funding InformationThis study was supported by Brain Korea 21 plus program by Ministry of Education of Korea (22A20130012421).
Activation of AMP Kinase by Zyflamend, a Well‐Defined Blend of Herbal Extracts
Authors: MacDonald Amber Frances , Han Anna Frances , Donohoe Dallas , Whelan Jay 
Published: November 2023

Zyflamend, a select blend of 10 herbal extracts, has been shown to inhibit prostate cancer (PCa) in vitro and in vivo at human equivalent doses. Zyflamend's tumor suppressive effects are partly due to the phosphorylation and activation of 5′ adenosine monophosphate‐activated protein kinase (AMPK), a master energy sensor of the cell that restores homeostasis in response to metabolic stress. AMPK activation by Zyflamend inhibits lipogenesis and enhances mitochondrial fatty acid oxidation, depriving proliferating tumor cells of necessary fatty acids for the generation of new membranes (Zhao et al, 2015). However, the mechanism of action whereby Zyflamend phosphorylates AMPK (pAMPK) is unknown. Currently, the literature has identified four kinases that phosphorylate the catalytic subunit of AMPK at Thr172, thereby increasing activity. Two of these kinases that most likely activate AMPK in PCa are liver kinase B1 (LKB1) and calcium/calmodulin‐dependent protein kinase kinase β (CaMKKβ). First, inactivation of LKB1 is associated with a variety of cancers, including reduced expression in PCa tissue. In addition, knockdown of LKB1 promotes the proliferation of PCa. Second, CaMKKβ has been negatively associated with castrate‐resistant PCa, where decreased expression increases proliferation and over expression reduces tumor growth in vivo. Therefore, the objective of this study was to determine the upstream kinase of AMPK activation by Zyflamend in castrate‐resistant PCa cells. CWR22Rv1, a castrate‐resistant PCa cell line, expresses LKB1 and CaMKKβ. When cells were treated with chemical inhibitors of LKB1 (radicicol) or CaMKKβ (STO‐609), pAMPK was reduced. Treatment with Zyflamend in the presence of radicicol failed to completely restore pAMPK at Thr172, while pAMPK was restored to the Zyflamend‐stimulated levels in the presence of STO‐609. These data suggest that Zyflamend‐stimulated pAMPK is partially dependent upon LKB1, but independent of CaMKKβ activity.Support or Funding InformationSupported by the Tennessee Agricultural Experiment Station Hatch grant #TEN00441
Genetic Background Determines Anthocyanin Effects on Glutathione Redox Balance
Authors: Norris Katie M , Pazdro Robert 
Published: November 2023

BackgroundAnthocyanins are secondary plant metabolites that provide the blue, red, and purple color of many plants. In recent years, these compounds have generated considerable interest among biomedical researchers due to their reported health benefits. It has been proposed that commonly consumed anthocyanins, such as cyandin‐3‐O‐β‐glucoside (C3G), confer cellular protection by increasing biosynthesis of glutathione (GSH), an endogenous antioxidant. However, it is unclear whether anthocyanin‐induced health effects are subject to genetic control. In this project, we tested the hypothesis that genetic background regulates anthocyanin‐induced alterations in GSH levels and redox balance (GSH/GSSG).MethodsFemale mice representing five genetically diverse inbred strains (A/J, 129S1/SvImJ, CAST/EiJ, C57BL/6J, and NOD/ShiLtJ) were assigned to a control (n=5/strain) or 100 mg/kg C3G diet (n=5/strain) for six weeks. Liver, kidney, heart, pancreas, and brain were collected, and levels of GSH and GSSG were quantified by high‐performance liquid chromatography (HPLC). Total glutathione was calculated as GSH + 2GSSG, and redox balance was assessed by the GSH/GSSG ratio.ResultsC3G treatment increased GSH/GSSG in the livers (p = 0.041) and hearts (p = 0.028) of CAST/EiJ mice. C3G increased renal GSH levels (p = 0.01), increased total renal glutathione (p = 0.014), and decreased pancreatic GSSG levels (p = 0.021) in this strain as well. C3G‐treated C57BL/6J mice exhibited increased GSH/GSSG ratios in the pancreas (p = 0.042) only. NOD/ShiLtJ mice exhibited no differences between control and C3G treatment in any of the tissues, and no significant differences were found with C3G treatment in the brain in any of the five strains. Surprisingly, C3G negatively affected GSH levels in two strains. A/J mice fed a high C3G diet exhibited lower hepatic GSH concentrations (p = 0.044) and GSH/GSSG ratios (p = 0.017) compared to controls. 129S1/SvImJ mice also exhibited lower hepatic GSH/GSSG ratios (p = 0.007) with C3G treatment. In this strain, C3G also increased GSSG levels in the liver (p = 0.02) as well as decreased total glutathione in the heart (p = 0.034) compared to controls.ConclusionsTo our knowledge, this study is the first to show that the biological effects of anthocyanins are determined by genotype. This study also demonstrates that these effects occur in a tissue‐specific manner. Our data will inform future efforts to clarify genetic mechanisms that regulate differential responses to anthocyanin supplementation.
Proteomic analysis of human serum of osteopenic women after dried plum treatment
Authors: Lee Fanny , Ghassemian Majid , Schenk Simon , Kern Mark , Hooshmand Shirin 
Published: November 2023

Dried plum has the ability to prevent and reverse bone loss as evidenced by an increase in bone mineral density as well as changes in bone turnover biomarkers such as insulin growth factor‐1, bone‐specific alkaline phosphatase, tartrate‐resistant acid phosphatase‐5b and sclerostin. However, it is not known whether dried plum affects other proteins in human serum that may influence bone turnover. The objective of this study was to explore if dried plum affects proteins in human serum other than the known bone turnover biomarkers related in the reversal of bone loss in osteopenic postmenopausal women using isobaric tags for relative and absolute quantification (iTRAQ). Serum samples were obtained from forty‐eight osteopenic women (65–79 years old) who were randomly assigned to one of three treatment groups for six months: 1) control 2) 100g dried plum or 3) 50g dried plum. Samples were collected at baseline and after three and six months of intervention. The iTRAQ quantitative proteomics approach was conducted to explore the proteome affected by dried plum treatment. iTRAQ results identified 51 unique proteins that were upregulated with at least a 2‐fold difference in change between control and treatment groups (p<0.05). Twenty‐four proteins were significantly upregulated only at 3‐months, five proteins at both 3‐ and 6‐months and eighteen at 6‐months only. Of the relevant proteins, ten proteins relate to inflammation, at least 5 relate to immunological function in general, five relate to lipid metabolism and one has a known direct association with bone metabolism. Dried plum treatment resulted in an upregulation of 51 unique proteins in human serum, which may or may not be linked to bone turnover. Future studies must be conducted to determine if these are in fact related to bone turnover processes.Support or Funding InformationPilot Award from UCSD CTRI (UL1 TR000100)