bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hepatotoxicity of Ochratoxin A, Benzo [a] pyrene and Acrylamide, Alone and in Combination with HepG2 Cell through Phase I and Phase II Pathway
Authors: Shin Hye Soo , Pyo Min Cheol , Bae Hyun‐Sun , Bae Jung Min , Lee Kwang‐Won 
Published: June 2021

Ochratoxin A (OTA) is a widespread mycotoxin produced by several species of the genera Aspergillus and Penicillium. Since OTA is mainly found in foods such as rice and oats consumed all over the world, there are many researches on the reduction of OTA. Benzo [a] pyrene (B[a]P) and acrylamide (AA) may occur during the heat treatment process to reduce the OTA present in rice. In this study, we tried to identify the combined toxicity of the three substances (OTA, B[a]P, AA) in the liver. The cell viability of OTA, B[a]P and AA was checked to determine the concentration of IC20. The toxicity of the combination of the three substances showed synergistic effects on cell viability and NO production. To further elucidate the mechanism of toxicity in liver, real‐time PCR was used to confirm mRNA expression levels of enzymes involved in phase I and II pathway. In the case of cytochrome P450 (CYP) families (CYP1A1, CYP1A2, and CYP3A4) belonging to Phase I, the mRNA expression levels were significantly increased when all three of them were mixed with each other than those treated with OTA, B[a]P and AA, respectively. The mRNA expression levels of heme oxygenase‐1 (HO‐1) and glutamate cysteine ligase catalytic subunit (GCLC) belonging to Phase II were also similar to those of Phase I. Therefore, in all experiments, the combined toxicity of OTA, B[a]P, and AA was confirmed, indicating synergistic effects on hepatotoxicity.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Coordinated Cross‐talk between calcium and cAMP in regulating pulsatile insulin secretion: A novel role for the unique inhibitory G‐protein, Gαz, in regulating β‐cell function
Authors: Schaid Michael , Harington Jeff , Wienkes Haley , Merrins Mathew , Kimple Michelle 
Published: June 2021

Cyclic adenosine monophosphate (cAMP) is an important secondary messenger involved in a variety of signal transduction mechanisms. In the pancreatic β‐cell, cAMP amplifies pulsatile insulin secretion through protein kinase A (PKA) and the exchange protein activated by cAMP (EPAC). Inhibition of adenylyl cyclase (AC) limits glucose stimulated insulin secretion, even in the absence of activated stimulatory proteins, suggesting an essential role of cAMP in β‐cell function. It has been proposed that cAMP may coordinate with calcium oscillations to regulate pulsatile insulin secretion; however, this has not been demonstrated in intact islets under physiological conditions. In this study we utilize a β‐cell‐specific, genetically encoded cAMP biosensor expressed in intact isolated mouse islets to demonstrate for the first time an anti‐phasic relationship between cAMP and Ca2+ oscillations. This suggests that intracellular cAMP levels are governed by the Ca2+ sensitive phosphodiesterase, which act to degrade intracellular cAMP during the active phase of insulin exocytosis. Furthermore, loss of the inhibitory G‐protein alpha‐subunit, Gαz, an important contributor to diabetes pathology, increased the amplitude of cAMP oscillations and sensitivity to glucagon like peptide‐1 (GLP‐1) receptor stimulation. Ligand activation of E‐prostanoid receptor 3 (EP3), a G‐protein coupled receptor (GPCR) up regulated in the diabetic state that couples to Gαz, reduces cAMP oscillations but also dramatically blunts Ca2+ oscillations. These results suggest a coordinated cross‐talk between Ca2+ and cAMP dynamics in the β‐cell, as well as a novel role for Gz signaling which acts on both Ca2+ dynamics and inhibition of the cAMP‐mediated amplifying pathway of insulin secretion.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
THE BIOLOGICAL IMPACT OF THE GOLGI MEMBRANE PROTEIN TMEM165 FOR BREAST CANCER
Authors: Murali Pavitra , Johnson Blake , Climer Leslie , Oprea‐Ilies Gabriela , Lupashin Vladimir , Abbott Karen 
Published: June 2021

The TMEM165 gene encodes for a multiple pass membrane protein, localized in the Golgi that has been linked to congenital disorders of glycosylation. We have identified TMEM165 as a biomarker for breast carcinoma in a previous glycoproteomic study. The TMEM165 protein is not expressed in non‐malignant breast tissue, increases slightly in early stage ductal carcinoma in situ (DCIS) cases, and is highly expressed in invasive ductal breast cancer. Our hypothesis is that TMEM165 confers a growth advantage to breast cancer. In this preliminary study we created a CRISPR/Cas9 knockout of TMEM165 in the human invasive breast cancer cell line MDAMB231. Our results indicate that removal of TMEM165 in these cells results in a significant reduction of cell migration and tumor growth in vivo. These studies illustrate new potential functions for this Golgi membrane protein in the control of tumor cell growth and invasion.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Investigation of PKHD1L1's Localization and Potential Function as a Tumor Suppressor
Authors: Shi Xingyi , Yoo Lina 
Published: June 2021

The Polycystic Kidney and Hepatic Disease 1‐like 1 (PKHD1L1) gene located on human chromosome 8 has been shown to have a high frequency of mutation in multiple types of epithelial cancers, such as skin, lung, and bladder cancer, according to data generated by the TCGA Research Network; its mutation rate in bladder urothelial carcinoma (11.41%) was ranked 65 among 19,578 genes analyzed. Furthermore, the TCGA data demonstrated that PKHD1L1 gene expression was diminished compared to normal tissues in those epithelial tumors. Our approach was to examine PKHD1L1's potential tumor suppression functions in bladder cancer cell line UM‐UC‐3. We engineered a CRISPR‐Cas9 PKHD1L1‐gRNA expression vector, which was then transfected into UM‐UC‐3 cells. After selection and establishment of clonal cell lines, mutation of full‐length PKHD1L1 was confirmed to be successful via TIDE analysis showing complete, frame‐shift disruptions. We performed wound healing assays, MTS assays, and colony formation assays to examine the impact of full‐length PKHD1L1 deficiency on cell motility and proliferative capacity. Wound healing assays and MTS assays showed no significant difference due to PKHD1L1 deficiency. Preliminary studies suggest PKHD1L1 deficiency may result in larger and more numerous colonies in the colony formation assay. We are currently investigating the subcellular localization of PKHD1L1 protein through immunocytochemistry. With further investigation, our research can provide significant insight into the role of PKHD1L1 in cancer development and progression.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Correlation of Oyster Disease with Vibrio Parahaemolyticus accumulation in oyster tissue
Authors: Jackson Kiserian , Scro Abigail , Smolowitz Roxanna 
Published: June 2021

As the average water temperature of Narragansett Bay and other coastal ponds in Rhode Island continue to increase due to climate change it is probable that the abundance of Vibrio parahaemolyticus (Vp) and Vibrio vulnificus (Vv) will increase as well. Vibrio are gram‐negative bacteria that can accumulate in tissues of the eastern oyster (Crasssostrea virginica). While vibrio is not pathogenic to the oyster it can cause gastroenteritis in humans that consume the raw oysters. Eastern oysters are commonly infected with three diseases: Perkinsus marinus (Dermo), Haplosporidium nelson (MSX) and Haplosporidium costale (SSO). These parasites can cause severe morbidity and mortality in cultured and wild oysters. Animals that are affected by any disease have a decreased immune functionality and it is probable that these diseased oysters are more likely to accumulate higher levels of Vp and Vv. To test this theory, oysters were collected from Roger Williams University during the summers of 2016 and 2017. Composites of 10 oysters were tested using multiplex qPCRs for Vp and Vv in conjunction with a second multiplex qPCR to determine the abundance of those three disease. Individuals were also tested in order to increase accuracy of the association because composites which produce averages may mask important relationships only identified in individual animals.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Dendropanax improve kidney function by inhibiting oxidative stress via upregulating sirt‐1 in Streptozotocin‐induced diabetic rats
Authors: Sachan Richa 
Published: June 2021

ObjectiveThe objective of the study was to evaluate the effect of Dendropanax (DP) for its efficiency in ameliorating diabetes and its associated nephropathy with its possible underlying protective mechanisms.The present study was designed to evaluate the protective effect of Dendropanax (DP) morbifera against nephrotoxicity in streptozotocin (STZ)‐induced diabetic rats. Diabetes was induced by a single injection streptozotocin (50 mg/kg, i.p.). The water extract of DP (400 mg/kg body weight) was administered by oral gavage for 4 week. We measured body weight changes, blood lipid parameters, blood glucose, glucose tolerance, insulin sensitization, blood urea nitrogen (BUN), creatinine, AST, or ALT. In addition, we measured the expression of SIRT‐1, extracellular matrix, oxidative stress, and fibrosis markers. Administration of DP in STZ‐induced diabetic rats significantly improved glucose tolerance and insulin sensitization. The levels of serum glucose, insulin, total protein, albumin, triglycerides, cholesterol, low density lipoprotein cholesterol (LDL‐C), creatinine was significantly increased in STZ‐induced diabetic rats. In diabetic rat model, DP significantly reversed the serum levels of BUN and creatinine and decreased serum 3‐indoxyl sulfate levels, a new nephrotoxicity biomarker in STZ‐induced rats. In particular, the protective effects of DP on diabetic‐induced renal injury were clearly exhibited by analysis of histopathological examination in STZ‐induced rats. In particular, oxidative stress‐mediated pathway in diabetic nephropathy was closely associated with NF‐kB and TGF‐β1 pathways. The protective effects of DP on diabetic‐induced renal injury were clearly exhibited by analysis of histopathological examination on the kidney. We demonstrated that DP extracts protects diabetic‐induced renal injury by blocking oxidative damage via SIRT‐1 activation which indicating its clinical application to inhibit diabetic‐induced chronic kidney disease (CKD).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Antihyperglycemic, nephroprotective and antioxidative effects of white and yellow Discorea domentorum yam based‐diet in alloxan‐induced diabetic rats
Authors: Ajayi Olubunmi Bolanle 
Published: June 2021

The present study was convened to assess the effects of white and yellow Discorea domentorum yam (Trifoliate yam tubers) based‐diet on biochemical parameters in alloxan‐induced diabetic rats for 14 days. Experimental rats were divided into four groups (n=6): Group 1: normoglycemic group which were fed corn starch‐based diets; group 2: diabetic control group fed corn starch based diet; group 3 and 4 served as diabetic test groups fed white and yellow Discorea domentorum yam flour‐based diets respectively. The results revealed elevation of blood glucose levels in diabetic control rats fed corn starch‐based diets when compared to the normal control rats. Moreover, increased blood glucose levels were suppressed significantly (P < 0.05) in diabetic rats fed white and yellow trifoliate‐based diets. Furthermore, reduced activities of superoxide dismutase (SOD) and catalase (CAT) as well as decreased levels of reduced glutathione (GSH) and malondialdehyde (MDA) were observed in diabetic control rats fed corn starch‐based diets when compared to normal control rats and diabetic rats fed white and yellow Discorea domentorum yam flour‐based diets. In addition, urea and creatinine levels were significantly (P < 0.05) increased in diabetic control rats fed corn starch‐based diets when compared to the normal control rats. However, white and yellow Discorea domentorum yam flour‐based diets significantly (P < 0.05) increased SOD and CAT activities, GSH and MDA levels while reduced urea and creatinine levels in treated diabetic rats but not up to control levels. The results suggest that the Discorea domentorum yam flour based‐diet may attenuate hyperglycemia, nephrotoxicity and oxidative stress in diabetic condition.Support or Funding InformationNILThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Anti‐adipogenic and Anti‐diabetic Activities of Patchouli Alcohol
Authors: Lee Jihye , Lee Seong‐Ho 
Published: June 2021

Patchouli alcohol is a sesquiterpene alcohol found in Pogostemon cablin. We reported that patchouli alcohol showed anti‐inflammatory and anti‐cancer activities in murine macrophages and human colon cancer cell lines. However, its effect on metabolism remains questionable. The current study was designed to investigate if patchouli alcohol affects adipogenesis and insulin sensitivity using differentiated adipocytes and myocytes, respectively. Treatment of patchouli alcohol (50, 75, and 100 μM) reduced lipid accumulation in 3T3‐L1 adipocytes in a dose‐dependent manner without toxicity. Treatment of patchouli alcohol increased expression of non‐phosphor and total β‐catenin in 3T3‐L1 adipocytes. On the other hand, treatment of patchouli alcohol (25 and 50 μM) significantly increased glucose uptake in differentiated C2C12 cells, which is associated with increased phosphorylation of Akt, AMP‐activated protein kinase α (AMPKα), insulin receptor substrate‐1 (IRS‐1), and β‐catenin. We demonstrated that β‐catenin might mediate beneficial effect of patchouli alcohol on prevention of adipogenesis and enhanced glucose uptake.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Obesity‐Related Stressors Repress Gonadotropin‐releasing Hormone Gene Expression via the Transcription Factor c‐Fos
Authors: Moseman Warren , Bertsch Alec , Walsh Heidi E. 
Published: June 2021

In obesity, endoplasmic reticulum (ER) stress is a well‐characterized mediator of hormonal dysfunction in multiple tissues, including liver, pancreas, and adipose tissue. In the brain, ER stress induced by excess nutrients and inflammatory cytokines disrupts insulin and leptin sensitivity in hypothalamic neurons controlling food intake. Obesity‐related cellular stressors may also disrupt hypothalamic control of the reproductive system, as obesity is a risk factor for infertility in both men and women. Thus, we sought to determine how ER stress and nutrient excess directly affect production of gonadotropin‐releasing hormone (GnRH) by hypothalamic neurons. GnRH controls pituitary gonadotropin release and subsequent gonadal function, and expression of the Gnrh1 gene is regulated by multiple transcription factors and signaling pathways. Using an immortalized mouse hypothalamic cell line (GT1‐7), we determined that ER stress induced by tunicamycin or thapsigargin repressed expression of the Gnrh1 gene as measured by qRT‐PCR. We also exposed cells to a saturated fatty acid (palmitic acid) to mimic excess nutrients in obesity and observed similar Gnrh1 repression. Both ER stress and palmitic acid promoted inflammation in GT1‐7 cells, as measured by NFκB and JNK activation and IL‐6 production. Repression of Gnrh1 by ER stress was partially rescued by PKC and JNK inhibitors. Because ER stress and palmitic acid upregulated expression of Fos, and because c‐Fos is a known repressor of Gnrh1, we asked whether inhibition of c‐Fos transcriptional activity could rescue Gnrh1 repression. The c‐Fos/AP‐1 inhibitor T5224 was able to completely reverse repression of Gnrh1 by ER stress and palmitic acid, indicating a pivotal role for c‐Fos induction in Gnrh1 repression by obesity‐related stressors. Thus, our work suggests that obesity‐related stressors can directly impact GnRH neurons, and that dysregulation of Gnrh1 expression may contribute to obesity‐related infertility.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Changes in Spexin Levels are influenced by the Presence or Absence of Gestational Diabetes in Pregnant Subjects
Authors: Aldaghri Nasser 
Published: June 2021

ObjectiveThe study aimed to determine whether circulating spexin (SPX) is modified during the course of pregnancy and whether it is affected by the presence of glucose intolerance.MethodsThis prospective follow up study involved 47 pregnant women (26 non‐GDM and 21 GDM; mean age 31.0 ± 5.4 years; mean BMI 28.2 ± 5.8 kg/m2). Anthropometrics, glycemic and lipid profile as well adipocytokines and spexin were measured at baseline and after 3 and 6 months.ResultsIn GDM patients, SPX levels increased significantly after 6‐months, along with the significant increase in glucose during the same time (p=0.04). In non‐GDM patients, median SPX level decreased significantly from baseline to 6‐months (p<0.01) but no such significant change in glucose was observed. Change in glucose from baseline to 6‐months was significantly and positively associated with change in SPX in GDM patients only (R= 0.45; p<0.05).ConclusionsChanges in SPX levels seem to be influenced by the presence of glucose intolerance (GDM) among pregnant women, with decreasing levels among those without GDM, and increasing among those with GDM.Support or Funding InformationThe study was funded by Prince Mutaib Chair for Biomarkers of Osteoporosis (PMCO), Deanship of Research Chairs in King Saud University, Riyadh, Saudi ArabiaThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Molecular characterisation of small molecule agonists and internalisation of GLP‐1R
Authors: Kanamarlapudi Venkateswarlu 
Published: June 2021

The glucagon‐like peptide 1 receptor (GLP‐1R) is one of the most promising therapeutic targets for the treatment of type 2 diabetes (T2D).1 It is well documented that GLP‐1R agonists, GLP‐1 and exendin‐4, stimulate glucose‐dependent insulin secretion and increase beta cell proliferation and survival. These observations resulted in approval of both GLP‐1 agonists, Liraglutide (a stable form of GLP‐1) and Exenatide (a synthetic version of exendin‐4) for the treatment of T2D.2 The inconvenience of long‐term administration of injectable peptide therapeutics (Liraglutide and Exenatide) has necessitated discovery of orally active small molecules agonists, compounds 2 and B, of the GLP‐1R. The agonist occupied GLP‐1R signals through both the Gαs and Gαq coupled pathways to stimulate insulin secretion. The coupling of GLP‐1R to the Gαs pathway results in cAMP production whereas the receptor coupling to the Gαq pathway leads to intracellular Ca2+ accumulation and ERK phosphorylation (ERK‐p). However, our recent study revealed that compounds 2 and B induce cAMP production similar to GLP‐1, but not intracellular Ca2+ accumulation, ERK‐p.3 Agonist induced GLP‐1R internalisation is important for insulin secretion. We have also shown that inhibition of the Gαq pathway but not the Gαs pathway reduces the GLP‐1R internalisation.4 Consistent with this, compounds 2 and B, which activate only the Gαs pathway, shown to fail in inducing the GLP‐1R internalisation.3 Chemical inhibitors of the Gαq pathway significantly reduced the agonist induced GLP‐1R internalisation and suppressed ERK‐p, demonstrating phosphorylated ERK acts downstream of the Gαq pathway in hGLP‐1R internalisation.4 We have also assessed the importance of both ends (N‐ and C‐termini) of GLP‐1R for its trafficking.5,6 In my presentation, I will discuss our recent findings on small molecule agonists and internalisation of GLP‐1R.Support or Funding InformationThis work was partially supported by Biotechnologyand Biological Sciences Research Council UK (BB/C515455/2 and BB/F017596/1) and Medical Research Council UK(G0401232).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Does this gene make me look fat? ATP10A Expression in Targeted Human Populations
Authors: Hurst Sarah Elizabeth , Ward Taketa , Hall Brandon , Smolinski Kasia 
Published: June 2021

Globally, the prevalence of type 2 diabetes (T2D) and diet‐induced obesity (DIO) is increasing due to higher energy intake and lower energy expenditure. However, the mechanisms that underlie these diseases remain unclear as numerous genes are implicated. ATP10A has been associated with several metabolic abnormalities in animal and in vitro models, so for this pilot study, we sought to identify the expression of ATP10A in targeted human populations. Based on the responses from the medical surveys, subjects were divided into three target groups based on body mass index (BMI), and five groups based on waist‐to‐height ratio (WtHR). From collected saliva samples, total RNA were extracted and analyzed using semi quantitative real‐time PCR (qRT‐PCR). Our results showed significant differences in the BMI groups by one‐way ANOVA [F (2, 6) = 49853, p < 0.0001] with the highest fold change in ATP10A seen in the overweight population (58.12) and the lowest in the normal weight population (32.28). When classified using WtHR, results again showed significance [F (4, 10) = 944735, p < 0.0001] with the overweight, obese, and highly obese groups having greater fold changes (10.56, 9.15, and 11.96 respectively) when compared to slender (0.19) and healthy groups (0.77). Collectively, these results suggest that ATP10A may play an important role in obesity and other metabolic disorders, and as such, we believe the results from this pilot study are promising and worth further exploration.Support or Funding InformationFunding for this work was provided by donations to The ATP10A project.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.