bluuebunny/crossref_metadata_2025_split huggingface dataset:
Strain‐specific profiles of hepatic xanthones in mice chronically fed α‐mangostin, the most abundant xanthone in mangosteen fruit (1044.7)
Authors: Chitchumroonchokchai Chureeporn , Mah Eunich , Gutierrez‐Orozco Fabiola , Bruno Richard , Failla Mark 
Published: June 2021

Little is known about the tissue distribution and metabolism of ingested mangosteen xanthones . We investigated hepatic content and profiles of xanthone metabolites in four murine strains (C57BL/6, Athymic nude, C3H and BALB/c mice; n = 5 group) fed AIN‐93G diet containing 0.1% α‐MG‐rich mixture of xanthones for 4 weeks. α‐MG accounted for 88.5% of dietary xanthones with γ‐MG, garcinone D and others representing 3.7%, 3.0% and 4.8%, respectively. Estimated xanthone intake during the feeding trial was approximately 300 nmoL/g BW. Mice were fasted for 4h before necropsy. Hepatic xanthones were extracted without and with glucuronidase/sulfatase to assess free and conjugated compounds. The presence and concentrations of xanthones in diet and liver was determined by LC‐MS. Hepatic concentration of total xanthones was greatest in C57BL/6 mice (15 ± 6 nmol/g) followed by C3H (9.4 ± 5 nmol/g), Athymic nude (8.8 ± 4 nmol/g), and BALB/c mice (3.1 ± 0.8 nmol/g). α‐MG accounted for 77‐82% of hepatic xanthones in C57BL/6, C3H and Athymic nude mice, but only 55% in BALB/c mice. Relative concentrations of garcinone D and 9‐hydroxy‐calabaxanthone in liver accounted for 9‐15% and 6‐14% of total xanthones, respectively, which exceeded their percentage in diet. Approximately 80% of xanthones in liver were phase II conjugates. Results suggest that dietary xanthones and their metabolites are present in murine liver, that various dietary xanthones are biotransformed, preferentially accumulated in liver and/or eliminated, and that absorption and/or whole body metabolism of these compounds appears is/are influenced by genotype.Grant Funding Source: CAFFRE and OSU CCC MCC
Anti‐inflammatory bioactives in Alaskan seaweed: implications in metabolic syndrome (1045.14)
Authors: Kellogg Joshua , Esposito Debora , Komarnytsky Slavko , Lila Mary Ann 
Published: June 2021

A dominant factor underlying the development of metabolic syndrome is abdominal obesity, which is associated with chronic inflammation in adipose tissue. Alaska Native populations, who suffer disproportionately high rates of obesity, have shifted away from traditional dietary foods, like seaweeds, that are a rich source of polyphenols with potential to counteract metabolic syndrome. In this work, Alaskan seaweeds Fucus distichus (FD), Saccharina latissima (SL), Saccharina groenlandica (SG), Alaria marginata (AM), Pyropia fallax (PF), and Ulva lactuca (UL) were evaluated for their potential to ameliorate symptoms of obesity‐linked inflammatory pathways. High levels of phenolics were discovered in ethyl acetate and butanol fractions of AM, FD, and SG (326.8 ‐ 557.2 μg phloroglucinol equivalents (PGE)/mg extract). Fractions of AM, FD, SG, and SL reduced nitric oxide levels in LPS‐induced RAW 264.7 macrophages to basal levels, and assays with 3T3‐L1 adipocytes demonstrated that organic fractions of AM, SL, and UL decreased triglyceride accumulation 13.3 ‐ 24.7%. Subsequent analysis of AM fractions revealed reductions in mRNA expression levels for the inflammatory adipokines IL‐10, MCP‐1, iCAM, and TNF‐α by 92.6%, 50.7%, 67.3%, and 65.4%, respectively. These results support the potential of Alaskan algae to reduce inflammation and obesity in adipose tissue.Grant Funding Source: Supported by the UNC General Administration and NCSU's Plants for Human Health Institute
Purple‐fleshed potato, even after processing, prevents and reverses high‐fat diet elevated colonic‐mesenteric fatősystemic inflammation cascade in pig model (1045.47)
Authors: Radhakrishnan Sridhar , Kim Sung , Reddivari Lavanya , Vanamala Jairam 
Published: June 2021

High‐fat diet (HFD) elevated colonic/adipose tissue inflammation strongly correlates with lipopolysaccharide (LPS) induced TLR‐4 activation. We have previously shown that purple‐fleshed potatoes (PP) suppress colonic/systemic oxidative stress markers in HFD consuming pigs. We hypothesized that PP, even after processing; suppress HFD induced colonic/mesenteric fat inflammation via suppression of LPS/TLR‐4 signalling compared to white‐fleshed potatoes (WP). We performed 2 studies ‐ a prevention study where 64 pigs consumed one of the 8 diets: Standard diet (SD), HFD and HFD supplemented with raw/baked/chips PP or WP (10% w/w) for 13 wk; and a reversal study where pigs (12 wk on HFD) consumed HFD containing 10/20% PP or WP chips for 5 wk (n=8). In the prevention study, all potato diets suppressed (P < 0.05) HFD elevated colonic/mesenteric fat expression of TLR‐4 and downstream NF‐κB and TNF‐α (qPCR), and serum IL‐1β (Immunoassay). In the reversal study, colonic/mesenteric fat expression of TLR‐4, NF‐κB and TNF‐α were consistently suppressed only in PP group (not WP) compared to HFD control (P < 0.05), suggesting that time of intervention is important. In addition, PP extracts suppressed LPS or TNF‐α induced NF‐κB activation in Caco‐2 cells compared to WP. Collectively, these results suggest that PP were more potent in reversing the HFD elevated colonic‐mesenteric fat‐systemic inflammatory cascade.Grant Funding Source: Supported by USDA‐NIFA NRI Grant 2009‐55200‐05197
1’‐Acetoxychavicol acetate inhibits adipogenesis in 3T3‐L1 adipocytes and in high fat‐fed rats (1045.7)
Authors: Kojima‐Yuasa Akiko , Ohnishi Rie , Deguchi Yohei , Yaku Keisuke , Tabuchi Masaki , Munakata Hiroshi , Matsui–Yuasa Isao 
Published: June 2021

The compound 1’‐acetoxychavicol acetate (ACA), which is naturally obtained from the rhizomes and seeds of Languas galangal and Alpinia galangal, is the pungent component of galangal and has various biological properties, including anti‐inflammatory, anti‐allergic and antitumor properties. In this study, we investigated the anti‐obesity effects of ACA in 3T3‐L1 adipocytes and in a high fat diet (HFD)‐induced rat model of obesity.ACA caused a significant decrease in the activity of glycerol‐3‐phosphate dehydrogenase (GPDH) in 3T3‐L1 adipocytes without eliciting cell cytotoxicity, and it inhibited cellular lipid accumulation through the down‐regulation of transcription factors such as PPARγ and C/EBPα. ACA also induced a dose‐dependent phosphorylation of AMP‐activated protein kinase (AMPK). In the animal model, rats fed an HFD containing 0.05% ACA gained less weight than rats fed an HFD alone. The visceral fat mass in rats fed an HFD containing 0.05% ACA tended to be lower than that in rats fed an HFD alone. Furthermore, a histological examination of livers from rats fed an HFD showed steatohepatitis. However, rats fed an HFD containing 0.05% ACA showed no histopathological changes in the liver tissue.Our results show that ACA exerts anti‐obesity activities both in vitro and in vivo and suggests that ACA may have a novel preventive activity against obesity and possibly other metabolic diseases.
Characterization of force sensing apparatus in human periodontal ligament fibroblasts (1046.10)
Authors: Macarak Edward , Braud Martin , Wei Wenjie , Giglou Kamyar , Howard Pamela 
Published: June 2021

Characterization of force sensing apparatus in human periodontal ligament fibroblasts A putative force transfer complex (FSC) similar to that found in muscle tissue (dystrophin glycoprotein complex or DGC) has been characterized in human periodontal ligament fibroblasts (HPDLFs). Similar to the DGC, the FSC is a physical bridge that links the cell to the basement membrane (BM). HPDLFs were also subjected to compressive strain in vitro to mimic that used in orthodontic tooth movement and its effects on the gene expression of 14 genes evaluated.Methods: Using immunohistochemistry and Western blotting, HPDLFs were characterized with respect to either the presence or absence of DGC and BM components. To evaluate the effects of compressive force on HPDLF gene expression, mRNAs were quantified by RT‐ PCR.Results: DGC and BM proteins localized to HPDLFs by immunohistochemistry and further characterized in HPDLFs extracts by Western blotting; however, dystrophin was not identified. RT‐PCR revealed significant changes in gene expression of α‐sarcoglycan (p = 0.0009) and γ‐sarcoglycan (p < 0.0001), collagen III (p = 0.0191), and laminin (p = 0.0077) in HPDLFs that underwent cyclic compression.Conclusions: DGC and BM proteins, with the exception of dystrophin, are present in HPDLFs. Cyclic compressive forces caused significant changes in gene expression of some DGC and ECM components.
Regulation of versican expression by bacterial infection is TLR4‐dependent but MyD88‐independent (1046.3)
Authors: Chang Mary , Delaney Martha , Hajjar Adeline , Wight Thomas , Frevert Charles 
Published: June 2021

In the acute response to bacterial lung infection, gram‐negative bacteria activation of toll‐like receptors (TLRs) stimulates macrophages to secrete a variety of molecules that lead initially to pulmonary inflammation and, ultimately, to resolution of inflammation. Using immunohistochemistry and qPCR we have shown that versican, a chondroitin sulfate proteoglycan, co‐localizes with macrophages in the lungs of mice with gram‐negative pneumonia, and is produced by alveolar and bone marrow‐derived macrophages (BMDM) exposed to live E. coli or lipopolysaccharide (LPS) in vitro. The goal of the current study is to define the TLR signaling pathway responsible for versican production by macrophages. BMDM were isolated from wild‐type mice (WT) and mice lacking TLR2 (TLR2 KO), TLR4 (TLR4 KO), or MyD88 (MyD88 KO). Versican mRNA was detected at low levels in untreated BMDM from all mice. In WT BMDM, versican mRNA was significantly increased by 4 h after treatment with 10 ng/ml LPS (50.5 ± 10.8‐fold vs PBS control; n = 3, p < 0.0001), and returned to basal levels by 24 h. The versican response to LPS was similarly elevated in TLR2 KO BMDM but was completely abrogated in TLR4 KO BMDM, indicating that LPS induction of versican is mediated by TLR4. Further, the response in MyD88 KO BMDM (48.3 ± 5.0‐fold vs PBS control; n = 3, p < 0.0001) was similar to that in WT BMDM, indicating that LPS induction of versican is MyD88‐independent. Further studies to define downstream signaling components in more detail are in process and will contribute to our understanding of the pro‐ vs anti‐inflammatory role of versican in the acute response to bacterial infection.Grant Funding Source: Supported by HL098067 & RR030249
CoCl2, chemical inducer of Hif1‐alpha, and CD44 expression in salivary glands malignant neoplasm cell line (1047.2)
Authors: Soave Danilo , Celes Mara Rubia , Ribeiro‐Silva Alfredo 
Published: June 2021

Introduction: The use of neoplastic cell lines to evaluate and understand the biological behavior of neoplastic cell is widely spread. Some studies argue that hypoxia promotes the genetic instability, ability to evade apoptosis, increased aggressiveness, as well as promotes extracellular matrix breakdown, tumor progression and metastasis. CD44 is involved in cell‐cell, cell‐matrix interactions and their expression seems to be unregulated in many tumors.Objective: the present study evaluated the chemically induced hypoxia and CD44 expression in salivary glands malignant neoplasm cell line.Material and Methods: The chemically induced hypoxia was achieved by exposing normoxic cultures of HTB‐41 (ATCC) cells to CoCl2. The cells were plated (5x105 cells/well) and incubated with medium alone ( or 50, 150, 300 μM of CoCl2 for 24 h at 37 ̊C, 5% CO2. The chemically induced hypoxia was identified and evaluated through analysis of Hif1‐α, CAIX, Glut1 and then correlated to CD44 expression through Western Blotting assay.Results: The present study demonstrated that HTB‐41 supports the CoCl2 stimulus in different concentrations (50, 150, 300 μM). We also observed that Hif1‐α, CAIX and Glut1 expression were associated with chemically induced hypoxia and the expression were accentuated at 300 μM CoCl2. However, we observed that CD44 expression was decreased in chemically induced hypoxia.Conclusion: In summary, we presented evidence that Hif1‐α; CAIX and Glut1 expression were associated with chemically induced hypoxia at different concentrations. Additionally, CD44 expression seems to be down regulated in the hypoxic microenvironment.Grant Funding Source: Suported by FAPESP (2011/18427‐5)
Upregulation of ADP‐ribosylation factor 1 contributes to the enhanced activation of the MAPK ERK1/2 in prostate cancer cells (1047.4)
Authors: Davis Jason , Teng Yong , Guo Jianhui , Wu Guangyu 
Published: June 2021

It is well known that the hyperactivation of the MAPK ERK1/2 pathway correlates with the progression of prostate cancer. However, the molecular mechanism responsible for the enhanced activation of this pathway remains ambiguous. Our recent studies have demonstrated that ADP‐ribosylation factor 1 (ARF1), a Ras‐related small GTPase that has been well‐characterized to coordinate vesicle‐mediated intracellular trafficking, regulates the activation of the Raf1‐MEK‐ERK1/2 pathway (Dong C., et al.: J. Biol. Chem. 286:43361‐43369, 2011). This prompted us to define the function of ARF1 in activating ERK1/2 in prostate cancer cells. We found that both ARF1 expression and ERK1/2 activation were markedly augmented in human metastatic prostate cancer cells compared to normal prostate cells. Conversely, the total expression of ERK1/2 was significantly downregulated in prostate cancer cells. To further confirm whether ARF1 expression level is directly linked to ERK1/2 activation, we determined the effect on ERK1/2 activation of lentiviral‐mediated overexpression of ARF1 in normal prostate cells and shRNA‐mediated depletion of ARF1 in prostate cancer cells. Our results showed that ERK1/2 activation was dramatically increased in cells overexpressing ARF1, whereas ERK1/2 activation was markedly decreased in cells infected with shRNA targeting on ARF1. These data have demonstrated for the first time that the enhanced activation of the MAPK ERK1/2 pathway in prostate cancer is at least partially induced by ARF1 upregulation. These data also suggest that, by virtue of its ability to activate the MAPK ERK1/2, ARF1 may play an important role in the progression of prostate cancer.Grant Funding Source: Supported by: NIH RO1GM076167
BMI‐1 silencing significantly reduces gene expression of DNA damage repair markers in human breast cancer (1047.5)
Authors: Silveira Giórgia , Celes Mara , Soave Danilo , Oliveira‐Costa João Paulo , Ribeiro‐Silva Alfredo 
Published: June 2021

Homologous recombination has a major role in DNA double‐strand break repair. BMI‐1 has been associated with cell immortalization through the supression of INK4a/ARF locus, thereby allowing that DNA double‐strand breaks occur. However, the influence of BMI‐1 in homologous recombination markers is still poorly understood. Our objective was to evaluate the influence of BMI‐1 silencing on expression of homologous recombination genes, cell proliferation and cell damage. BMI‐1 was silenced through lipofectamine‐based siRNA (Invitrogen). We accessed gene expression through Real‐Time PCR reactions in MCF‐7 cell line. Cells were subjected to MTT assay for determination of proliferation rate. Immunofluorescence was also performed to access BMI‐1 and γH2AX (DNA damage marker) protein expression. BMI‐1 silenced cells proliferated significantly less than control (p<0.001). BMI‐1 silencing significantly reduced ATM (p<0.001), ATR (p<0.001), BRCA‐1 (p=0.001), BRCA‐2 (p<0.001), H2AX (p=0.001), TP53 (p<0.001), RAD51 (p<0.001) and TOP3β (p=0.037) expression. Immunofluorescence staining showed that cells positive for BMI‐1 were also positive for γH2AX, while silenced BMI1 cells had reduced expression of γH2AX (nuclear staining). Our results showed that BMI‐1 positive cells may have a more aggressive behavior in breast cancer.Grant Funding Source: Supported by: FAPESP (2011/23845‐2)
Metallothioneins are potential prognostic biomarkers in breast cancer patients (1048.11)
Authors: Malepati Dhananjaya , S Lakshminarasaiah 
Published: June 2021

Metallothioneins (MTs) are highly conserved low molecular weight proteins. The main functions of MTs are binding, chelating and detoxification of various toxic substances. It also protects tissue damage from reactive oxygen species, radiation and mutagens. MTsexpression levels were evaluated in order to determine its role in different clinical stages of breast tumors during pre‐ and post‐ menopausal women. In the present study the expression levels of metallothioneinisoforms MT‐1F, MT‐1E and MT‐2A were assessed by semi‐quantitative PCR in breast carcinoma tissues of seventy two individuals. Similarly, MT levels were also quantified in non tumor breast tissue samples of respective individual subjects, during different clinical stages of pre‐and postmenopausal breast cancer patients through RT‐PCR technique..The percentage of expression levels were quantified by integrative density value (IDV). As the stage progresses the selected MT isoforms expression also increases in both pre‐ and post‐ menopausal breast tumors. This indicates that the MTs expression is closely associated with pre and postmenopausal malignant tumors along with non tumor tissues. So, MT isoforms are promising prognostic biomarkers in the prospective patient studies and may be validated to establish MT assays for use in clinical practice. Therefore the MT assays may be used as the Diagnostic tools in the diagnosis and treatment of women breast cancer.Grant Funding Source: INDIAN GOVT. FUNDING AGENCIES
Histomorphologic characterization of human tissues stained with selected plant‐based dyes (1050.10)
Authors: Bassey Rosemary , Hu Yan , Tomaszewski John , Nickerson Peter , Holmes Jasmine , Colón Luis , Osinubi Abraham , Oremosu Ademola 
Published: June 2021

Background: The use of eco‐friendly natural dyes has become a matter of significance due to increased environmental awareness. However, the scientific studies and systematic reports with natural dyes are insufficient. In this study, we have explored the histomorphological properties of several plant‐based dyes.Methodology: Paraffin‐embedded human tissue sections were stained with a variety of plant‐based dyes sourced from Nigeria to determine factors that produce the optimal staining efficiency in the dyes. The stained tissues were studied under bright‐field and also using a multi‐spectral imaging system to histomorphologically analyze the staining characteristics on the different tissues.Results: The staining characteristics and factors influencing staining efficiency of the different dyes on human tissues were determined. L. cyanescens stained the nuclei and cytoplasm with strong nuclear labeling in all the tissues. H. sabdariffa selectively and strongly labeled the nuclei in the tissues stained. The deep pink from H. sabdariffa and the blue from L. cyanescens gave good contrast, making a good combination for staining of tissues.Conclusion: Our study has shown L. cyanescens and H. sabdariffa as effective, cheap and readily available histological stains derived from our rich biota.
In vivo demonstration of okadaic acid internalization in glutamatergic spinal motor neurons (1050.3)
Authors: Torres‐Vazquez Irma , Torrech‐Santos Christian , Serrano‐Velez Jose , Rein Kathleen , Rosa‐Molinar Eduardo 
Published: June 2021

The development of new techniques and reagents has facilitated the detailed study and characterization of endocytic pathways. We used okadaic acid (OA), a naturally occurring toxin produced by marine dinoflagellates of the genus Prorocentrum, that is a potent and selective inhibitor of the serine/theorine protein phosphatase, phosphoprotein phosphatase 1, combined with a minimally invasive method to retrogradely label neurons and their processes in an adult spinal motor circuit. We demonstrate the prevalent expression of connexin 35 gap junction proteins and plaques at dendrodendritic excitatory mixed synapses between spinal motor neurons and interneurons. In addition, we discovered that OA appears to be entering spinal motor neurons through a clathrin‐independent internalization mechanism that we are currently investigating.Grant Funding Source: Supported by MH‐086994; NSF‐10 62963, and NSF‐0964114
Simvastatin, atorvastatin, and pravastatin are equally effective in improving the hemodynamic status of type 1 diabetic rats (1051.14)
Authors: Quidgley Jose , Cruz Nildris , Melendez George , Crespo Maria 
Published: June 2021

Statins improve cardiovascular (CV) status of diabetic patients. The underlying mechanisms remain unclear. We compared the effects of a four‐week administration of 10 mg/kg/day atorvastatin (AV), simvastatin (SV), and pravastatin (PV) on the CV function of (STZ)‐diabetic rats. Echocardiographic parameters, endothelial function, cholesterol levels, perivascular fibrosis and oxidative stress markers were evaluated. Cholesterol levels (mg/dl) were higher in STZ (249±16) than in CT (156±7) (n=10, P<0.05), and were not modified with this statin dose. AV and SV improved ejection fraction, stroke volume and cardiac output index (n=10, P<0.05), while PV only improved ejection fraction and stroke volume. Vascular relaxation was improved by all statins, and abolished by 1 mM LNAME, suggesting a NO‐dependent mechanism. In addition, all statins significantly reduced perivascular fibrosis (µm/100g BW) from 10.59±0.40 in untreated STZ to 9.0±0.3 (AV), 8.8±0.4 (SV), and 9.0±0.4 (PV), and levels of the oxidative stress markers MDA and 4‐HAE. The cholesterol‐independent hemodynamic benefits observed with all statins may be secondary to reductions of oxidative stress. The latter, by improving endothelial function, will reduce vascular tone and remodeling, decrease cardiac workload and improve systolic performance.Grant Funding Source: Supported by MBRS‐RISE R25‐GM061838.
Sex‐based alteration of relative importance of EDRFs in modulating vascular reactivity in Zucker diabetic fatty rats (1051.15)
Authors: Shaligram Sonali , Han Xiaoyuan , Zhang Rui , Anderson Leigh , Rahimian Roshanak 
Published: June 2021

Little is known about interaction of sex and diabetes in vasculature. Our study investigates the effects of type 2 diabetes on endothelium‐dependent and ‐independent relaxations. Also, if there are sex‐based changes in relative contributions of endothelium derived relaxing factors (EDRFs) in modulating vascular reactivity of mesenteric arteries (MA) from ZDF rats. Relaxation responses to acetylcholine (ACh) in MA pre‐contracted with phenylephrine (PE) were obtained before and after pretreatment with indomethacin (cyclooxygenase inhibitor), L‐NAME (nitric oxide synthase inhibitor) or barium chloride (Kir blocker) plus ouabain (Na+‐K+‐ATPase inhibitor). Vascular responses to sodium nitroprusside (SNP) were also measured in MA. ACh‐induced relaxations were significantly impaired in MA of diabetic rats, regardless of sex. In diabetic females, the relative importance of endothelium derived hyperpolarizing factor (EDHF) in relaxation to ACh was reduced, while in diabetic males, role of nitric oxide (NO) was reduced. Interestingly, relaxation to SNP was enhanced in diabetic animals, irrespective of sex. In summary, the relative importance of NO and EDHF in regulating vascular tone of rat MA is altered in type 2 diabetes with respect to sex. Furthermore, increased smooth muscle sensitivity to NO may be an attempt to compensate for impaired endothelial function in both diabetic male and female rats.Grant Funding Source: Supported by NIDCR