bluuebunny/crossref_metadata_2025_split huggingface dataset:
Discovery of Bacteria in Meconium of Normal, Uncatheterized, and Uninfected Late‐Gestation Fetal Sheep
Authors: Doerr Beau E , Keller‐Wood Maureen , Wood Charles Evans 
Published: June 2021

Fetal development is thought to proceed in a sterile environment. Recent reports of the presence of bacterial DNA in human placenta, the transfer of live bacteria from mother to fetus after hypoxia in the pregnant sheep, and the presence of bacteria in the meconium of newborn infants have suggested that the fetus might be exposed to bacteria in utero. We performed the present studies to build on our discovery of bacterial rRNA in the meconium of normal fetal sheep. Specifically, the present experiments were designed to test the hypothesis that intact bacteria could be visualized histologically in meconium from normal, uncatheterized, and uninfected fetal sheep. Pregnant ewes, uncatheterized and free of clinical disease, were euthanized in late gestation. At necropsy, meconium was isolated from fetal colon using RNAse and DNAse‐free instruments and snap‐frozen, then stored at −80C until analyzed. Approximately 150 mg of meconium was homogenized and both RNA and DNA extracted in Trizol. RNA was isolated, converted to cDNA using random hexamers, then subjected to endpoint PCR using primers 341F and 806R that amplify a 465 bp region of bacterial 16S rRNA. All assays were performed with both positive and negative controls. In meconium, 7/7 fetuses (143 days gestation; term=147 days) harbored bacterial RNA. Smears of meconium were stained using Gram stain or hematoxylin stain. Gram stain revealed Gram positive and Gram negative organisms with morphologies that are consistent with the genus/species of bacteria that we have previously identified in meconium using 16S rRNA gene sequencing in DNA isolated from meconium. Hematoxylin staining confirmed the morphology of bacteria observed in the Gram‐stained samples. Bacteria in meconium appear in clusters that are consistent with live, replicating, organisms. The present results support previous work from this laboratory demonstrating that bacteria gain access to the normal fetal sheep. These results are consistent with our observations that bacteria are present in low numbers in amniotic fluid. It is possible that amniotic fluid containing bacteria is swallowed by the fetus, that bacteria survive the transit through the immature fetal gastrointestinal tract, and that the bacterial population expands in the nutrient‐rich environment of the fetal colon.Support or Funding InformationThis work was supported by HD033053 and AI120195.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Effects of a histone methyltransferase inhibitor on fertility in an animal model of endometriosis
Authors: Seguinot Inevy Ivtchelle , Craig Zellieann , Isidro Angel , Flores Idhaliz 
Published: June 2021

Endometriosis is an inflammatory, painful gynecologic disease with no cure and limited treatment options. Epigenetics, including histone modifications, play a key role in the etiology of endometriosis, therefore it has been hypothesized that epigenetic drugs can be used as a non‐hormonal therapeutic alternative for endometriosis. Following up on our observation that treatment with a histone methyltransferase inhibitor (HMTi) significantly decreased disease parameters such as size of vesicles in an animal model of endometriosis, this study was designed to investigate the effects of HMTi on fecundity correlates (e.g,. changesin expression of fertility‐associated genes and in ovarian and endometrial histology). Two weeks after endometriosis induction in female Sprague Dawley rats, we injected rats intraperitoneally with HMTi or vehicle for four weeks. At sacrifice, the ovaries and uterus of the rats treated with HMTi or vehicle were collected. mRNA was extracted from the right ovary for qPCR of fertility associated genes (ER, LH, CYP19) and secondary and antral follicles were counted in the left paraffin‐embedded ovary. The uterus was paraffin‐embedded to evaluate histopathological parameters. Treatment did not modify the expression of any of the genes studied, and did not significantly affect the number of ovarian follicles compared to vehicle. In addition, HMTi did not cause any histopathological changes in uteri compared to vehicle. These observations suggest that HTMi does not negatively influence fecundity in this model, a possibility that is currently being investigated in vivo.Support or Funding InformationSpecial thanks to our funding from Puerto Rico Science, Technology & Research Trust, PHSU RISE (NIGMS Grant R25GM062406), PHSU Magic Core & Brain Core (NIMHD Grant MD007579), Puerto Rico Biobank (NCI Grant 1U54CA163071), PRISE Program from University of Puerto Rico, Ponce Campus (NIGMS Grant R25GM096955) and Porter Physiology Development Fellowship.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Use of Photobiomodulation and Mesenchymal Stem Cells in Polycystic Ovary Syndrome‐Induced Rats
Authors: Alves Eduardo Donato , Benevenuto Luíz Guilherme Dércore , Amin Rebeca Gall , Donadoni João Antônio , Ferrari Kamile Bausells , Barros Michele Andrade , Achcar Jorge Alberto , Parizotto Nivaldo Antonio , Montrezor Luís Henrique 
Published: June 2021

Evaluation was made of glycemia and gonadosomatic index (GSI) variations in rats with induced polycystic ovary syndrome (PCOS), following application of photobiomodulation (PBM) and injection of mesenchymal stem cells (MSCs). Eighty adult Wistar rats (n = 10 per group) were divided into control (C), PCOS, PBM, MSC, PCOS/PBM, PCOS/MSC, PBM/MSC, and PCOS/PBM/MSC groups. PCOS was induced by single injection of estradiol valerate (EV) (2 mg/kg/bw/i.m.). The animals were evaluated 30 and 60 days after induction. MSCs were injected directly into the ovaries (5×105cells/0.2 mL physiological solution in each ovary), on the same day as PCOS induction. The animals were irradiated with a laser (wavelength 808 nm, power 60 mW), using a dose of 3 Joules(J)/point on each ovary, 3 times weekly, totaling 6 J of energy for each irradiated animal per day of application. After sacrifice, plasma glucose was determined and the ovaries were removed and weighed for GSI determination (ovary weight/body weight × 100). Statistical analysis of the data was performed using ANOVA and Fisher's test. The results were reported as means ± SEM. This study was approved by the local Animal Care and Use Committee (CEUA–UNIARA, protocol nº 019/16). Glycemia: There were reductions in glycemia for all exposed groups, compared to the 30‐day C group (260.2 ±37 mg/dL), with the lowest values for the PCOS/PBM/MSC group (103.6 ±12.58 mg/dL). Compared to the 30‐day PCOS group (186.2 ±79.7 mg/dL), glycemia was lower for groups PBM/MSC (115.6 ±15.32 mg/dL) and PCOS/PBM/MSC (103. 6 ±12.58 mg/dL). After 60 days of treatment, the PCOS/MSC group presented lower glycemia (101.8 ±20.03 mg/dL), compared to the C group (160.6 ±42.3 mg/dL). 30‐days GSI: The PCOS/PBM(0.019 ±0.006%), PCOS/MSC (0.018 ±0.0061%), PBM/MSC (0.029 ±0.02%), and PCOS/PBM/MSC (0.027 ±0.008%) groups showed increased GSI, compared to the C group (0.012 ±0.0013%). 60‐daysGSI: There were increases of GSI for the PCOS/MSC (0.013 ±0.0048%), PBM/MSC (0.02 ±0.0035%), and PCOS/PBM/MSC (0.017 ±0.0036%) groups, compared to the C group (0.008 ±0.0039%). The results indicated that the PBM/MSC combination reduced glycemia 30 days after PCOS induction by EV. In addition, the combined use of PBMand MSC resulted in higher GSI, 30 days after PCOS induction, compared to the PCOS group, which was indicative of ovarian modulations induced by this treatment. Morphological, immunohistochemical, and hormonal studies are underway in our laboratory to complement the present study.Support or Funding InformationFunding: FAPESP (Grant 2016/02811‐4)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
High Intensity Focused Ultrasound Treatment Attenuates Disease Progression in a Mouse Model of Non‐Alcoholic Steatohepatitis
Authors: Huerta Tomas S. , Devarajan Alex , Tsaava Tea , Chavan Sangeeta S. , Tracey Kevin J. 
Published: June 2021

Non‐alcoholic fatty liver disease (NAFLD), a widespread condition affecting approximately 35% of the US population, is characterized by excessive lipid accumulation in hepatocytes. Non‐alcoholic steatohepatitis (NASH) is a severe form of NAFLD that is characterized by hepatocyte inflammation alongside accumulation of fat in the liver. NASH can lead to cirrhosis and liver cancer. Recent studies suggest that activation of the inflammatory reflex that is mediated by vagus nerve can reduce the chronic inflammation often seen in metabolic disorders including NASH. Here, we utilize a preclinical model of NASH, which is induced by diet, to study the effectiveness of high‐intensity focused ultrasound (HIFU) in modulating specific hepatic neural networks and test HIFU as a therapeutic strategy. Mice in the NASH group were maintained on a high‐fat high‐carbohydrate (HFHC) diet consisting of 60% kcal from fat chow and sugar supplemented water (55% fructose, 45% sucrose), while the low‐fat diet (LFD) control group received 10% kcal from fat chow. After 8 weeks on these diets, animals received daily liver‐targeted HIFU or sham stimulation. Exposure to HIFU but not sham stimulation resulted in significant improvement in body weights (p > 0.05, t test) and blood glucose levels (p > 0.05 t test) in HFHC mice. Moreover, the body weight and blood glucose values of HIFU‐treated HFHC mice trended toward both LFD groups (HIFU‐treated and Sham‐treated). In addition, HIFU attenuated circulating pro‐inflammatory cytokines and metabolic disease markers in HFHC mice. HIFU improved glucose tolerance, reduced HOMA‐IR score, and resulted in less fat accumulation in the liver than Sham‐stimulated HFHC group. Collectively, these findings suggest that noninvasive HIFU stimulation of the liver is a potential therapy for the NASH phenotype. Further studies are necessary to elucidate the mechanism by which liver‐targeted HIFU stimulation reduces inflammation and hepatic fat accumulation.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Effect of a Probiotic and a Specifically Immunized Egg Powder on Blood C‐Reactive Protein in a Subclinical Population
Authors: Skelton Michele , DelCastillo Daniel , Music Gary , Owens Makayla , Tracey Megan 
Published: June 2021

The purpose of this study was to examine the effects of a specifically immunized egg powder taken with a probiotic on blood C‐Reactive Protein (an inflammatory marker) in healthy subjects with subclinical GI complaints. In a randomized, double‐blind placebo‐controlled study, sixteen subjects were divided into two groups. One group received a probiotic plus 2 grams of a specifically immunized egg powder (treatment group) while the other group received a placebo. Blood C‐Reactive Protein (CRP) was measured prior to supplementation and immediately after a 4‐week supplementation phase. There was no change in the blood CRP for the placebo group. Blood CRP for the treatment group was reduced and approached significance (p=.07). The treatment group had a greater percent change in blood CRP compared to the placebo group (p < 0.05). Preliminary analysis suggests that a combination of a probiotic and a specifically immunized egg powder may contribute to lower blood CRP levels in healthy subjects with subclinical GI complaints.Support or Funding InformationIgY NutritionThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Dietary TMAO Exerts Beneficial Effects in Heart Failure Rats
Authors: Ufnal Marcin , Huc Tomasz , Drapala Adrian , Samborowska Emilia , Konop Marek 
Published: June 2021

Increased plasma trimethylamine oxide (TMAO) has been suggested to be a marker of cardiovascular risk. However, mechanisms of the increase and biological effects of TMAO are obscure. Plasma TMAO originates from gut bacteria‐produced TMA, and from dietary TMAO e.g. seafood.Male, 6‐week‐old, Spontaneously‐Hypertensive‐Heart‐Failure rats (SHHF, SHHF/MccGmiCrl‐Leprcp/Crl, Charles River Laboratories, USA) and 4–5‐week‐old Spontaneously Hypertensive Rats (SHR, Medical University of Warsaw, Poland) were divided into Water‐groups and TMAO‐groups (drinking TMAO water solution 0.33g/L). Age‐matched Wistar‐Kyoto (WKY) were used as healthy controls. After one year of observation survival was 100% in WKY, SHHF‐TMAO, SHR‐Water and SHR‐TMAO but only 66% in SHHF‐Water. WKY showed no pathological changes in the circulatory system. SHHF showed heart failure with reduced systolic function and hypertrophic cardiomyopathy with histopathological picture of transition from hypertrophic to dilated cardiomyopathy. SHR showed heart failure with reduced diastolic function and hypertrophic cardiomyopathy. In comparison to SHHF‐Water, SHHF‐TMAO had 3‐fold higher plasma TMAO, a significantly lower sympathetic/vagal ratio, and a trend toward lower cardiac fibrosis. In comparison to SHR‐Water, SHR‐TMAO had 4–5‐fold increase in plasma TMAO, significantly lower plasma NT‐proBNP, significantly lower left ventricle end‐diastolic‐pressure and significantly lower cardiac fibrosis.In conclusion, 3–5‐fold increase in plasma TMAO does not exert negative effects on the circulatory system in heart failure rats. In contrast, increased dietary TMAO seems to exert beneficial effect in heart failure, however, its magnitude may vary in different models or in different stages of heart failure.Support or Funding InformationSupported by National Science Centre, Poland grant no. 2015/19/N/NZ5/00650 and 2016/21/B/NZ5/02544.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Western Diet‐Induced Metabolic Memory and Persistent Vascular Dysfunction in Female Rats
Authors: Persand Dhandevi , Sepulveda Maria Alicia Carrillo 
Published: June 2021

Metabolic memory is a phenomenon by which the body remembers previous exposure to metabolic stressors, such as hyperglycemia. Consumption of a western diet (WD) is a major part of modern life contributing to the epidemic of Metabolic Syndrome (MS), a significant risk factor for cardiovascular disease. Recent studies from our laboratory have characterized a model of WD induced MS in female rats. If not treated early, MS often progresses to Type II Diabetes Mellitus (T2DM). Adopting a healthier diet prior to onset of T2DM may be sufficient to reverse the constellation of metabolic symptoms associated with MS including hyperglycemia, hypertriglyceridemia, and increased body fat around the waist. However, it remains unclear if this diet reversal overcomes metabolic memory and cardiovascular dysfunction associated with MS. We hypothesize that cardiovascular dysfunction will persist despite diet reversal due to the development of metabolic memory. Eight‐week old female Wistar rats were fed a WD (21% fat, 50% carbohydrate (34% sucrose), 20% protein) for 17 weeks (WD group) to induce MS. Then, the rats were subjected to diet reversal for 8 weeks (rWD group). The control group received a regular chow diet (5% fat, 48.7% carbohydrate (3.2% sucrose), 24.1% protein). Metabolic (body weight, triglycerides, free fatty acids, glucose tolerance) and cardiovascular (blood pressure and vascular reactivity) parameters were assessed. WD group showed increased body weight, triglyceride levels, and systolic blood pressure characterizing MS. Moreover, fatty liver was observed in the WD group. As expected, rWD group exhibited improvement of all metabolic parameters and reversal of fatty liver (Figure 1). WD group showed marked increases in systolic blood pressure, measured via right carotid catheterization. Using wire myography, cumulative concentration curves were performed for acetylcholine and sodium nitroprusside. We found a significant impairment of endothelium dependent and independent vasorelaxation, respectively. Surprisingly, the rWD group did not decrease blood pressure (Figure 2) or improve impaired vasorelaxation. These results indicate that WD causes long‐lasting cardiovascular complications that are not alleviated by diet reversal. Our findings show for the first time that exposure to a WD can lead to metabolic memory in the cardiovascular system. We will extend our studies to examine potential mechanisms of metabolic memory leading to persistent cardiovascular dysfunction.Support or Funding InformationIn‐house Grant NYITThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Maternal exercise enhances brown adipose tissue development and thermogenesis in offspring mice challenged with high fat diet
Authors: Son Jun Seok , Liu Xiangdong , Chen Yanting , Tian Qiyu , Zhao Liang , Hu Yun , Chae Song Ah , Deavilla Jeanene , Zhu Mei‐Jun , Du Min 
Published: June 2021

Accumulating evidences point to the early developmental origins of obesity and its associated metabolic diseases, which are prevalent. Brown adipose tissue (BAT) dissipates fatty acids and glucose as heat and, thus, enhancing BAT thermogenic function can effectively prevent obesity and metabolic symptoms. Physical exercise becomes less common in modern societies and moderate exercise during pregnancy is recommended, but its effects in BAT development and metabolic health of offspring have not been examined.PURPOSETo investigate the effects of maternal exercise on BAT development and thermogenesis, and metabolic health of offspring challenged with high fat diet (HFD).METHODSAfter mating, female C57BL/6J mice were randomly assigned into two groups of control (CON) and exercise (EX), and exercise was performed throughout gestation every morning for 60 min at moderate intensity. At birth, the litter sizes were normalized to 6. After weaning, offspring mice were fed HFD (60 kcal% from fat) during 8 weeks. The BAT were collected from both male and female offspring mice at weaning and also after 8 weeks of HFD feeding. Statistical difference was analyzed using student's t‐test and/or one‐way analysis of variance (ANOVA).RESULTSAt weaning, there were increases in mRNA expression of BAT markers, Ucp1, Ppargc1a, Prdm16, Elovl3, and Cox7a1 and protein levels of UCP1, PGC‐1α, and PRDM16 in female and male offspring born to EX compared with offspring from CON (P < 0.05). In addition, surface temperature of EX offspring was higher than CON. After 8 weeks of HFD, EX mice gained less body weight, had higher insulin sensitivity, and lower hepatic lipid accumulation (P < 0.05) compared to CON mice. The oxygen consumption rate, mRNA expression of Ppargc1a, Elovl3, and Cox7a1, and protein levels of UCP1, PGC‐1α, and PRDM16 remained higher in female and male EX offspring (P < 0.05).CONCLUSIONSExercise during pregnancy enhanced BAT development and thermogenesis in offspring, which protected offspring from obesity and metabolic syndromes when they consumed HFD, common in Western societies. Our data suggest that the lack of exercise of healthy women during pregnancy can predispose offspring to obesity and metabolic syndromes partially through impairing BAT function.Support or Funding InformationSupported by NIH Grant R01HD067449.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Mice Exposed to Early Life Stress Display Sex‐Specific Upregulation of Leptin Gene Expression in Adipose Tissue
Authors: Leachman Jacqueline Renee , Rea Matthew , Ritter Celia , Xu Xiu , Dalmasso Carolina , Fondufe‐Mittendorf Yvonne , Loria Analia S 
Published: June 2021

Epidemiological studies have established early life stress (ELS) as an independent risk factor for increased BMI and cardio‐metabolic disease later in life. We have previously shown that a mouse model of ELS, Maternal Separation and Early Weaning (MSEW), increases adiposity in weanlings and exacerbates high fat diet (HFD)‐induced fat expansion in a sex‐specific manner. Therefore, the aim of this study was to investigate the sex‐specific effects of MSEW on adipocyte‐derived production of important hormones for body weight homeostasis, such as leptin and adiponectin. MSEW was performed by separating the pups from the dam for 4 to 8 hours during postnatal days (PD) 2 to 16, and weaned on PD 17. Control mice remained undisturbed and were weaned on PD 21. Following, eight‐week‐old mice were then fed on either a low fat diet (LFD, n=6) or HFD (10 or 60 % Kcal from fat, n=6) for 12 weeks. Each litter was represented by one mice of each sex randomly assigned to each diet. Body composition trajectory was assessed by EchoMRI. At the end of the experiment, mice were sacrificed for adipose tissue collection. Leptin and adiponectin gene expression was performed in gonadal white adipose tissue (gWAT) and subcutaneous WAT (scWAT). After 12 weeks of HFD, male MSEW mice showed increased BW compared with controls (47.9 ± 1.1 vs. 40.2 ± 2.6 g, p<0.05) as well body adiposity (36.7 + 1.1 vs. 22.2 ± 4.1 % body fat, respectively). In female MSEW mice fed a HFD, but not in males, the gene expression of leptin in gWAT was significantly upregulated compared with controls (5.0 ± 0.5 vs. 3.6 ± 0.5, p<0.05), but not in scWAT (2.1 ± 0.6 vs. 1.5 ± 0.5, p<0.05). Despite sex‐specific changes in adiponectin gene expression in response to HFD, there was not a significant effect due to MSEW. To begin to address the mechanism by which MSEW increases leptin expression in a sex‐specific manner, we analyzed the site‐specific methylation of the leptin promoter in gWAT from mice fed a HFD (n=4). The methylation landscape in the leptin promoter was different between male and female mice. However, we found that CpG sites 3 and 15 were significantly hypomethylated only in fat from female MSEW mice comparted to controls (site 3: 21±1 vs. 52±1 %5mC, p<0.05; site 15: 84±1 vs. 100 %5mC, p<0.05). Both sites in the leptin promoter are strong areas for transcription factor binding. In addition, DNMT3A was upregulated in MSEW mice (p<0.05). Taken together, our current working hypothesis is focused on elucidating whether exposure to MSEW may promote the binding of specific transcription factors that upregulate leptin gene expression in a depot and sex‐specific manner.Support or Funding InformationR01HF135158 to ASL, R01HL135158‐01A1S1 to JRLThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.