bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibitory mechanisms of wheat germ and wheat/soy germ extract fermented with Aspergillus oryzae on human colorectal cancer HCT116 cells
Authors: Jang Hae-Dong , Song Ji-Hye , Choi So-Jin , Kim Eui-Su , Choi Hyung-Taek 
Published: June 2021

In this study, anti‐carcinogenic mechanism of wheat germ (WG) and mixed wheat and soy germ (WSG) extract fermented with Aspergillus oryzae were investigated in human colorectal cancer HCT116 cell model. The fermented WG and WSG extract reduced cell viability and increased the chromatin condensation, representing the characteristic of apoptosis death. The treatment of fermented WG and WSG extract increased the expression of apoptosis signals such as p53 accompanied with a marked increase in Bax, caspase‐3, and cleaved‐PARP. The fermented WG and WSG extract showed the invasion inhibitory effect of HCT116 cell model in matrigel invasion assay by crystal violet staining. The fermented WG and WSG extract decreased the expression of metastasis signals such as p‐Akt1, VEGF, MMP‐2, and MMP‐9. These results indicate that one of the plausible mechanisms underlying anti‐carcinogenic activity of fermented WG and WSG extract may involve the regulation of apoptosis and metastasis signals. The fermented WG and WSG could be used for the development of anti‐carcinogenic nutraceutical and pharmaceutical food.Grant Funding Source : ASN
Cinnamon extract inhibits angiogenesis in zebrafish and human endothelial cells by suppressing VEGF and PKC‐mediated MAP kinase
Authors: Bansode Rishipal R , Randolph Priscilla , Ahmedna Mohamed 
Published: June 2021

Current study is focused on the effects of cinnamon extract in modulating the pathway involved in angiogenesis. Human umbilical vein endothelial cells (HUVEC) were treated with cinnamon extract at a concentration of 100 μg/ml for 1, 3, or 6 hours (h) followed by treatment with phorbol ester (TPA) at a concentration of 10 nM to induce MAPK expression. Results show that cinnamon extract inhibited TPA‐induced phosphorylation of MAPK in a dose‐dependent manner. Gene expression results in HUVEC showed that cinnamon extract treatment inhibited TPA induction of PKC alpha mRNA expression in a dose‐dependent manner along with suppression of vascular endothelial growth factor receptor 1 (VEGFR1/Flt1) and vascular endothelial growth factor receptor 2 (VEGFR2/KDR/Flk1) mRNA expression.Cinnamon extract was administered to zebrafish embryos during gastrulation at 6–8 h‐post‐fertilization (hpf). The embryos were observed for changes in morphology, toxicity, and blood vessel development. The intersegmental vessels (ISVs) in the zebrafish embryos were attenuated and under‐developed at an effective cinnamon extract dose of 250 μg/ml compared to the DMSO‐treated control. Exposure to cinnamon extract for 36 h resulted in gross morphological deformities. The results suggest the effect of cinnamon extract on angiogenesis is mediated by PKC‐dependent phosphorylation of MAP kinase.
Anti‐inflammatory Effects of Cocoa Procyanidins
Authors: Gu Yeyi , Yu Shan , Lambert Joshua 
Published: June 2021

Inflammation, as evaluated by increased inflammatory cytokines and other markers, represents a link between obesity and its comorbidities. Cocoa (Theobroma cacao) is a procyanidin‐rich food with putative anti‐inflammatory effects; however, the mechanism of action remains to be fully elucidated. The objective of the present study is to determine the effects of cocoa procyanidins (CPs) with varying degree of polymerization (DP) on inflammatory markers related to eicosanoid metabolism and cytokine production using purified enzymes and cultured RAW 264.7 murine macrophage cells. CPs with DP ≥7 dose‐dependently inhibited purified phospholipase A2 (IC50 =3.2 μg/mL) and cyclooxygenase‐2 (IC50= 57.7 μg/mL) in vitro, and significantly decreased prostaglandin E2 production in lipopolysaccharide (LPS)‐stimulated macrophages. Pre‐treatment of macrophages with CP octamer (50 μM) significantly suppressed secretion of the proinflammatory cytokines tumor necrosis factor‐α (70%), interleukin‐6 (100%), monocyte chemoattractant protein‐1 (50%) compared to LPS‐stimulated controls. These results demonstrate the anti‐inflammatory effects of CPs and provide potential mechanistic biomarkers to be further tested in obese subjects under inflammatory conditions. This study was supported in part by a grant from Hershey Foods and by NIH Grant AT004678.Grant Funding Source: NIH Grant AT004678 and Hershey Foods
Involvement of AMPK on the synergistic upregulation of phase II detoxifying enzyme activities by 1′‐acetoxychavicol acetate and sodium butyrate
Authors: Yaku Keisuke , Matsui-Yuasa Isao , Kojima-Yuasa Akiko 
Published: June 2021

Introduction1′‐acetoxychavicol acetate (ACA) naturally obtained from the rhizomes and the seeds of the Zingiberaceae plant such as Languas galangal and Alpinia galangal. Butyric acid is one of major products of gut fermentation. Though ACA and sodium butyrate respectively upregulated phase II enzymes in intestinal epithelial cells (IEC 6), the interaction between these compounds is not clear. The present study was conducted to examine the interaction between ACA and sodium butyrate on regulation of phase II enzyme activities in IEC 6.MethodsGlutathione S‐transferase (GST) activity and NAD(P)H:quinine oxidoreductase 1 (NQO1) activity were measured by spectrophotometer. Nrf2 and p53 mRNA levels were estimated by RT‐PCR. Nrf2, p53, AMPK protein levels were examined by Western blotting.ResultsACA and sodium butyrate synergistically induced GST and NQO1 activities. These synergistic effects were inhibited with AMPK inhibitor, Compound C. Sodium butyrate upregulated the expression of Nrf2 mRNA and downregulated that of p53 mRNA, but ACA didn't affect those mRNA levels. The protein levels of intranuclear Nrf2 were increased by ACA or sodium butyrate. However, the combined treatment of ACA and sodium butyrate did not caused a synergic effect on level of intranuclar Nrf2. Intranuclar p53 protein level was increased by ACA, but It was decreased by sodium butyrate alone or by combined treatment of ACA and sodium butyrate. pAMPK levels were increased by combined treatment of ACA and sodium butyrate.ConclusionAMPK plays an important role on synergistic upregulation of phase II enzyme activities by ACA and sodium butyrate.Grant Funding Source : ASN
Hepatoprotective effects of Rubus coreanus Miquel concentrates on liver injuries induced by carbon tetrachloride in rats
Authors: Chyun Jong-Hee , Chae Hyun-Jung , Yim Jung-Eun 
Published: June 2021

As well‐being foods pursuing healthy life are getting popular, and interests for Rubus coreanus Miquel (RCM) fruit, kind of Korean blackberry, are heightening as its medical actions, which are protecting liver, brightening eyes, and in curing diabetes, are known. This study was carried out to evaluate hepatoprotective effects of RCM concentrates on liver injuries induced by carbon tetrachloride (CCl4) in rats.RCM, produced in June~July 2008 at Chunbook, Gochang, mashed fine. The seeds of RCM were removed and the juices were condensed. 32 Sprague‐Dawley rats were divided into normal group, CCl4 group (8 rats), 1% RCM group, and 2% RCM group. Experimental diets were provided to experimental animals for four weeks. We measure blood total cholesterol, HDL‐cholesterol, Glutamic oxaloacetic transaminase (GOT), Glutamic pyruvic transaminase (GPT), and Alkaline phosphatase (ALP). Part of the livers was separated for hitopathological observation, and measured lipid peroxide (TBARS) and liver protein.The activities of serum GOT, GPT and ALP were elevated by CCl4 administration and levels of hepatic TBARS were also significantly increased in CCl4 groups. However, the hepatic TBARS levels and activities of serum enzymes were markedly reduced by supplementation of the RCM concentrates (p<0.05). In histopathological observation, massive necrosis in centrilobular area and degenerative changes by CCl4 were recovered by dietary supplementation of RCM concentrates.These findings indicate that RCM concentrates have hepatoprotective effects and may improve symptoms of liver injuries.
Whey based formula reduces intestinal atrophy and enhances antioxidant defenses against sepsis
Authors: Tsutsumi Rie , Sasaga Sayaka , Takegawa Mariko , Sakai Tohru , Nakaya Yutaka , Tsutsumi Yasuo M. 
Published: June 2021

High quality whey protein has been shown that improve anabolism, GI tolerance, and antioxidant defenses. In this study, we assess the effect of whey based formula during the acute phase in the cecal ligation and puncture (CLP) mousemodel of sepsis. Male C57Bl/6 mice began whey based or casein based formula following induction of sepsis by CLP. Between 48 h to 7 days of sepsis, survival rate, intestinal histopathology, intestinal atrophy, antioxidant defense and serum levels of cytokines were assessed. Analyses were performed with StatView 5.0 (SAS Institute Inc., Cary, NC). Data are presented as mean±standard deviation (SD). P<0.05was considered statistically significant.Serum cytokines were higher in mice that underwent whey based formula vs control (TNFα;34.3±6.54 vs.67.6±8.93pg/ml, IL6;230+37 vs.443+49 pg/ml after 48 h induction, respectively). Whey‐based group showed re‐established total hepatic glutathione and glutathione disulfide (GSH/GSSG)levels. Whey‐based formula significantly improved intestinal atrophy which was measured by diamine oxidase (DAO) activity. Our data indicate that administering whey‐based formula after sepsis has several benefits by decreasing cytokines, increasing antioxidants and reducing intestinal atrophy.
Comparison of sterculic oil induced changes in the gut microbiota of lean and obese mice
Authors: Ghosh Shreya , Perfield James W. , Saikaly Pascal E. , Oerther Daniel B. 
Published: June 2021

Recent obesity research has reported differences in intestinal microbiota between obese ob/ob mice and lean wild type mice suggesting a potential link between bacterial populations and metabolic health. Sterculic oil (SO) is a natural inhibitor of stearoyl‐CoA desaturase‐1, a potential therapeutic target for the treatment/attenuation of obesity and insulin resistance.The aim of this study was to investigate the response of the obese and lean gut microbiota to a SO supplemented diet.Five‐week old male lean (WT) and obese (ob/ob) mice were fed either a control AIN‐93G diet or an AIN‐93G diet containing 0.5% SO for 9 weeks Barcoded pyrosequencing of the V4‐V5 region of the 16S rRNA gene was employed to characterize cecal microbiota.Intestinal microbiota from WT mice fed a control diet were more diverse, although there were no significant differences in the proportions of major phyla from WT and ob/ob mice. Irrespective of genotype, SO was negatively correlated with the relative abundances of Actinobacteria, Bacilli and Erysipelotrichi. This shift was not associated with a change in body weight, however a statistically significant improvement in glucose tolerance and insulin sensitivity was observed in the ob/ob mice fed SO. In our study, diet had a greater impact on gut microbiota as compared to genotype and these changes were associated with an improved metabolic health.Grant Funding Source : Missouri University of Science and Technology
Effects of claudins‐6, ‐7 or ‐9 overexpression on migration and invasiveness of breast and hepatocellular cancer cells
Authors: Salas Berenice , Rendón-Huerta Erika P. , Montaño-Estrada Luis F. 
Published: June 2021

Transmembrane proteins claudins preserve cell polarity and determine the size and charge of the molecules that pass through the paracellular space in epithelial tissues. Altered claudin expression in early and late stages of several cancers has been related to increased invasiveness and metastatic potential. We have reported an expression of claudin‐6, ‐7 and ‐9 in human gastric adenocarcinomas and their role in the human adenocarcinoma cells invasiveness. To determine if claudin overexpression confere advantages to breast and hepatocellular cancer cell lines, we evaluated the invasive capability of claudins transfected cells in Matrigel invasion chambers and by wound‐healing scratch assay. Proliferation rate by Brdu incorporation, and apoptosis of TNF treated cells by Anexin V detection were also measured. Overexpression of claudin‐6 or ‐9 resulted in increased migration and invasive potential; however claudin‐9 transfected cells migrated faster than the others.This work was supported by PAPIIT IN208910‐2.
Leptin Increases HER2 Stability through HSP90 in Breast Cancer Cells
Authors: Giordano Cinzia , Vizza Donatella , Rovito Daniela , Barone Ines , Bonofiglio Daniela , Panza Salvatore , Lanzino Marilena , Fuqua Suzanne , Catalano Stefania , Andò Sebastiano 
Published: June 2021

High serum levels of the adipocyte‐derived hormone leptin in obesity are a risk for breast cancer in postmenopausal women. The HER2/Neu receptor, overexpressed in 25% of human breast cancers, has been associated with endocrine resistance.Here, we evaluated the link between leptin and HER2 in human MCF‐7 breast cancer cells and in MCF‐7/HER2‐18 cells stably overexpressing HER2.We found that leptin treatment increased HER2 protein levels, without affecting HER2 mRNA levels. Leptin enhanced the expression of HSP90, a chaperone protein that regulates HER2 degradation, and increased HER2/HSP90 interaction. These events were dependent on JAK2/STAT3 activation, since inhibition of this cascade by AG490 or a STAT3 dominant negative abrogated leptin‐induced HER2 expression. Moreover, leptin treatment increased EGF‐mediated HER2, AKT and MAPK phosphorylation. Anchorage‐independent growth assays revealed that long term leptin treatment reduced sensitivity to the antiestrogen tamoxifen, while increased responsiveness to herceptin, a monoclonal antibody against HER2.We demonstrate that leptin, through HSP90, enhances HER2 stability, providing further insights into the crucial role of leptin in modulating tumor growth and aggressiveness. Clinically, our results suggest that leptin and HSP90 might be novel targets for therapeutic intervention in breast cancer, especially in obese patients.
Calcium channel blocking drugs ameliorates the experimental septic cardiomyopathy induced by cecal ligation and puncture in mice
Authors: Celes Mara Rubia N , Prado Cibele M , Campos Erica C , Malvestio Lygia M , Ferezin Patricia , Freitas Ana C.S. , Dias Priscila P. , Tanowitz Herbert B. , Rossi Marcos A 
Published: June 2021

ObjectiveThis study tested the hypothesis that verapamil (VP), an L‐type voltage‐dependent calcium channel inhibitor, and dantrolene (DT), a sarcoplasmic reticulum calcium inhibitor, could attenuate calpain overexpression, dystrophin loss/reduction and cardiac dysfunction in experimental sepsis by CLP.Methods and ResultsMale C57Bl/6 mice were subjected to sham and severe septic injury (SSI) induced by CLP; half of animals from each group were treated with either verapamil (5mg/kg, SSI+VP) or dantrolene (10mg/kg, SSI+DT). Reduced myocardial levels of NF‐kB and calpain‐1 were detected in SSI+DT and SSI+VP mice associated with increased actin and myosin expression as compared to SSI mice. Consonantly, DT and VP significantly prevented the loss of dystrophin in comparison with SSI mice. Concurrently, SSI+DT and SSI+VP mice presented ejection fraction and fractional shortening improvement associated with increased survival rate.ConclusionsThese observations give support to the opinion that increased intracellular calcium concentration induces calpain activation that causes dystrophin loss/reduction and consequent myocardial dysfunction in CLP experimental sepsis. Studies are needed to further elucidate these new possible interventional pathways to prevent septic cardiomyopathy/heart failure.
Expression of peroxisome proliferator activated receptor gamma coactivator 1 (PGC‐1) on the immune response to bacteria
Authors: Del Nero Luis Guilherme , Marta Guilherme , Lima-Salgado Thais , Kubo Sueli , Llimona Flávia , Velasco Irineu Tadeu , Souza Heraldo 
Published: June 2021

Introduction/ObjectiveInflammatory response during sepsis requires energy expenditure from immune cells. Since the transcription coactivator PGC‐1 controls cell energy homeostasis, we aimed to determine whether PGC‐1 may modulate the immune response in an experimental model of sepsis.MethodsLive bacteria were injected intraperitoneally in Balb/C mice and PGC‐1β expression was evaluated by quantitative PCR in peritoneal macrophages. Further, mice (20 animals in each group) were submitted to cecal ligation and puncture (CLP). Group 1 received intraperitoneal injections of antisense oligonucleotide (ASO) against PGC‐1β (3,0 nmol) three days before and three days after CLP. Group 2 was given no specific treatment. The animals were followed for 72 hours and mortality was evaluated every 12 hours.ResultsIncreased PGC‐1β expression was observed in macrophages from animals exposed to bacteria compared to controls (2.7±0.5 vs. 1.0±0.2, respectively, p<0.05). We further evaluated whether PGC‐1β absence would interfere with the response to acute bacterial aggression in vivo. Mice from Group 1, where PGC‐1β expression was blocked, showed an 80% mortality after 72 hours, while animals from Group 2 had a mortality rate of 63% (p=0,7714).ConclusionsPGC‐1β is up‐regulated during bacterial infection, however, abolishing PGC‐1β expression did not affect mortality of septic mice.Financial support: FAPESP
Cannabinoid Receptor Interacting Protein 1a (CRIP1a) regulates CB1 signaling and transcriptional activity
Authors: Blume Lawrence Christopher , Bass Caroline E. , Dalton George D. , Selley Dana E. , Howlett Allyn C. 
Published: June 2021

The CB1 cannabinoid receptor is the most abundantly expressed GPCR in the CNS and modulates many diverse neuronal functions related to synaptic plasticity and neuroprotection. The cellular actions of CB1 ligands on neuroprotection are poorly understood. A recent demonstration that the cannabinoid receptor interacting protein (CRIP1a) had the ability to switch CB1 neuroprotection from an agonist‐ to antagonist‐driven mechanism is intriguing (Stauffer et al., 2011 Neuroscience Letters). To better understand the role of CRIP1a in cytoprotection, we developed neuronal cell models to over‐express or knock‐down CRIP1a in order to identify changes in CB1‐mediated signal transduction and gene transcription. Data from On‐cell‐Western experiments indicate that over‐expression of CRIP1a significantly reduces the levels of phosphoERK, a downstream kinase and transcript factor activated by CB1. Additional studies focusing on phospholipase C and NFkappaB pathways demonstrated that modulation of CRIP1a produces alterations in the mRNA levels of c‐Fos, CCAAT/Enhancer binding protein (Cebpb), NF‐kappaB pathway and genes involved in cell survival and neuroprotection. These experiments suggest that CRIP1a may modulate CB1 signaling and transcription of genes that are important in stress and cell survival pathways.Supported by NIH grants T32‐DA007246, R01‐DA003690, R21‐ DA025321, K01‐DA024763.
Behavioral and metabolic changes in mice lacking Gβ5‐R7 complex
Authors: Wang Qiang , Levay Konstantin , Slepak Vladlen 
Published: June 2021

Gβ5 is a unique G protein beta subunit that dimerizes with R7 family RGS proteins instead of Gγ. Gβ5:R7 association is essential for stability of their complex and so the knockout of Gβ5 causes degradation of the entire Gβ5‐R7 family. Here we analyze the phenotypes of Gβ5 knockout (KO) and heterozygotes (HET) animals. The KO mice are lean, resistant to high fat diet, hyperactive and have lower serum insulin. The HETs are also slightly more active than the WT, but surprisingly, display signs of metabolic syndrome: late‐onset obesity, insulin resistance and liver steatosis. Thus, even a partial reduction in Gβ5‐R7 level causes distinct phenotypes. The expression of Gβ5‐R7 complexes was thought to be restricted to the nervous system. To understand the mechanisms involved in the etiology of Gβ5 KO and HET phenotypes, we re‐examined expression of Gβ5 complex in peripheral tissues. We found that it is present in glands, including adrenal and pancreas, with subsequent analysis of endocrine cells with ablated Gβ5 provides novel insights into the role of this complex.This study was supported by U.S. National Institutes of Health (NIH) grants GM 060019 (V.Z.S).
In vivo administration of LPS reduces dexmedetomidine‐induced contraction in isolated rat aortae
Authors: Manio Michael Magtoto , Man Ricky Y.K. , Vanhoutte Paul M , Ng Jacobus K.F. 
Published: June 2021

The vascular effects of dexmedetomidine during sepsis are largely unknown. The present experiments were designed to determine ex vivo responses to dexmedetomidine in arteries of animals after short‐ or long‐term exposure to lipopolysaccharide (LPS).Eight to ten weeks old male SD rats received different doses of LPS or normal saline in vivo two or 72 hours prior to sacrifice. Arterial blood pressure, heart rate and plasma cytokine levels were measured before isolating their aortae. Rings, with or without endothelium, were suspended in organ chambers, for isometric tension recording. In the absence or presence of pharmacological inhibitors [ L‐NAME, indomethacin, TRAM‐34, UCL1684 and iberiotoxin ].LPS injections increased the plasma levels of TNF‐á and IL‐6 and reduced arterial blood pressure. They dose‐dependently attenuated dexmedetomidine‐induced contractions whether given two or 72 hours prior to sacrifice. However, contractions were increased in preparations without endothelium, and to a lesser extent in rings with endothelium after 72 hours. In the presence of TRAM ‐34, but not UCL1684, dexmedetomidine‐induced contractions were enhanced on rings with endothelium, while they were reduced by iberiotoxin.The present data indicate that in vivo exposure to LPS differentially attenuates the contractile responses to dexmedetomidine, an action which may involve, BKCA .
RNA‐Seq identifies novel alternative transcripts of cytochrome P450s in human hepatocytes
Authors: Li Dan , Peng Lai , Lee In-Hee , Li Jennifer , Visvanathan Mahesh , Zhong Xiao-bo 
Published: June 2021

Most human genes can produce alternative transcripts by transcriptional regulation or RNA processing, which in many cases encode functionally distinct proteins. The cytochrome P450 enzymes (P450s) catalyze the oxidation of lipids, steroid hormones, drugs, and toxic chemicals. The purpose of this study was to identify novel transcripts of P450 genes and characterize their expression and induction in human hepatocytes. RNA sequencing (RNA‐Seq) was used to identify novel transcripts of P450s in human hepatocytes or HepaRG cells after treatment with rifampicin or phenobarbital. In 30 P450 genes with the expression levels >10 (FPKM: fragments per kilobase of exon per million fragments mapped) in human hepatocytes or HepaRG cells, RNA‐Seq identified 67 alternative transcription events, including exon skipping, intron retention, alternative splicing, and polyadenylation. Some events were reported in literature, but most were novel. Several novel events were confirmed by PCR or rapid amplification of cDNA ends plus DNA sequencing. Furthermore, differential expression of alternative transcripts was observed in some P450 genes after drug treatment.ConclusionRNA‐Seq identified novel transcripts for P450 genes. Alternative transcription variants of P450 genes had differential expression during drug treatments, which may serve as a potential mechanism for the differential enzyme activity in human liver.