bluuebunny/crossref_metadata_2025_split huggingface dataset:
Angiotensin‐(1–7) augments endothelium‐dependent relaxations of porcine coronary arteries to bradykinin by inhibiting ACE1
Authors: Vanhoutte Paul Michel , Wu Dongmei , Khang Gilson , Raffai Gabor 
Published: June 2021

Angiotensin converting enzyme 2 (ACE2) converts angiotensin II to angiotensin‐(1–7) that activates Mas receptors, inhibits ACE, modulates bradykinin (BK) receptor sensitivity. The present study compared the direct and indirect (on the response to BK) effect(s) of the ACE2 activator diminazene aceturate (DIZE) and angiotensin‐(1–7) in rings of isolated porcine coronary arteries, with or without endothelium, suspended in conventional organ chambers for isometric tension recording. In preparations contracted with U46619 (10−7 M), increasing concentrations of DIZE, angiotensin‐(1–7) or of the ACE inhibitor captopril, did not cause significant changes in tension before or after desensitization of BK receptors. B K caused concentration‐dependent and endothelium‐dependent relaxations which were inhibited partially by L‐NAME or TRAM‐34 plus UCL‐1684, but not by indomethacin. The response to BK was not affected by DIZE, but significantly potentiated, to a similar extent, by angiotensin‐(1–7) and captopril. The two compounds augmented the response in the presence of either L‐NAME or TRAM‐34 plus UCL‐1684, indicating potentiation of NO bioavailability and endothelium‐dependent hyperpolarizations, respectively. These results indicate that in coronary arteries angiotensin‐(1–7) enhances both endothelium‐dependent relaxations and hyperpolarization to bradykinin solely by ACE inhibition.Research support: World Class University program (R31–20029), Ministry of Education, Science and Technology, South Korea.
Investigation of the novel pharmacology of Neuropeptide Y (NPY) receptor dimers constrained by bimolecular fluorescence complementation (BiFC)
Authors: Kilpatrick Laura , Holliday Nicholas 
Published: June 2021

Dimerisation of GPCRs potentially influences their pharmacology via binding site cooperativity or modified signalling. We have used bimolecular fluorescence complementation (BiFC; Kilpatrick et al. (2012) Methods Mol Biol 897) to constrain Neuropeptide Y (NPY) Y1 receptor (Y1R) homo and heterodimers of known composition. Using quantitative platereader imaging we measured the internalisation of BiFC receptor dimers simultaneously with endocytosis of SNAP tagged Y1R protomer to compare the pharmacology of Y1/Y1, Y1/Y4 or Y1/Y5 BiFC dimers.Y1/Y1 and Y1/Y4 BiFC dimers internalised in response to NPY or PP (Y1/Y4), with potencies comparable to individually expressed YR subtypes. Endocytosis of Y1/Y1 or Y1/Y4 dimers to NPY was also inhibited by the Y1 antagonist BIBO3304, with expected pKb values ((8.2–8.5) from NPY concentration‐response curve shifts). However, the Y5 selective agonist PP(1–17)(Ala31, Aib32) NPY(18– 36) showed reduced potency for constrained Y1/Y5 BiFC dimers, compared to Y5‐GFP internalisation. BIBO3304 demonstrated a lower apparent affinity (pKb 7.4 ± 0.1) for Y1/Y5 BiFC dimers compared to the SNAP‐Y1 sub‐population (pKb 8.2 ± 0.4). This suggests an interaction between Y1 and Y5 orthosteric binding sites of Y1/Y5 BiFC dimers, with implications for selective targeting of this dimer as a mediator of central NPY appetite responses. LK is supported by the British Pharmacological Society.
Characterization of smooth muscle microRNA and mRNA genes that are regulated by actin polymerization
Authors: Albinsson Sebastian , Turczynska Karolina , Swärd Karl , Hellstrand Per 
Published: June 2021

The phenotype of vascular smooth muscle cells is regulated by multiple environmental cues including mechanical stretch. We have previously demonstrated that stretch‐induced actin polymerization is an important event for the expression of smooth muscle markers.The aim of this study was to characterize mRNA/proteins and microRNAs (miRNAs) that are regulated by actin polymerization to evaluate the role of this control mechanism for phenotypic modulation and vascular disease.Affymetrix chip gene arrays as well as miScript pathway focused miRNA PCR arrays were performed on smooth muscle cells treated with jasplakinolide, which stabilizes actin filaments.As expected a number of well‐known smooth muscle markers including calponin (Cnn1), myosin heavy chain (Myh11) and tropomyosin (Tpm2) were significantly up‐regulated by jasplakinolide treatment. We also confirmed that transcription of the newly identified smooth muscle markers Lmod1 and Kcnmb1 was induced by actin polymerization. In addition, our array data revealed a number of genes and miRNAs that were significantly affected by actin polymerization but which have not been previously identified as markers of the contractile smooth muscle phenotype.In conclusion, this study will lead to a better understanding of the regulation and importance of contractile smooth muscle markers and phenotypic modulation in the vasculature.
Does endothelial peroxisome proliferator‐activated receptor gamma (ePPAR‐γ) protect baroreflex function during obesity?
Authors: McCully Belinda H. , Duffy Kevin D. , Sigmund Curt D. , Brooks Virginia L. 
Published: June 2021

We tested the hypothesis that ePPAR‐γ protects baroreflex function during obesity by determining whether a long term (10–12 weeks, LT) or short term (1–2 weeks, ST) high fat diet (HFD, 45% kcal fat) impairs baroreflex gain (BRG) in mice with a dominant‐negative mutation of ePPAR‐γ (E‐V290M) more than wild‐type mice (WT). Arterial pressure and HR were measured by telemetry for 24hrs in mice on a 12:12 dark (D): light (L) cycle. Spontaneous BRG (sBRG; msec/mmHg) was derived using the sequence method. sBRG was lower in lean E‐V290M compared to WT during L, but not D. The LT‐HFD attenuated sBRG in WT and E‐V290M during both L and D, with no difference between groups. During L, the ST‐HFD also blunted sBRG in WT, and sBRG remained lower in E‐V290M mice. During D, ST‐HFD only lowered sBRG in E‐V290M. However, the ST‐HFD‐induced decreases in sBRG were not greater in E‐V290M compared to WT mice during L (WT: −0.30±0.05 vs E‐V290M: −0.17±0.04) or D (WT: −0.06±0.05 vs E‐V290M: −0.17±0.04), indicating that there was not an interactive effect between obesity and the ePPAR‐γ mutation on sBRG. These data suggest that while ePPAR‐γ supports BRG in lean mice, it does not protect the baroreflex during obesity.

sBRG (msec/mmHg)

Lean
L
D

WT (n=11)
1.63 ± 0.08
1.18 ± 0.06

E‐V290M (n=11)
1.28 ± 0.07†
1.08 ± 0.07

LT‐HFD

WT (n=5)
0.96 ± 0.18 #
0.84± 0.10 #

E‐V290M (n=3)
0.88 ± 0.19 #
0.69 ± 0.08 #

ST‐HFD

WT HFD (n=5)
1.36 ± 0.05#
1.10 ± 0.06

E‐V290M HFD (n=7)
1.12 ± 0.05†
0.89 ± 0.06†#

Data are mean ± SE.
P<0.05 group within diet,
P<0.05 diet within group
Child MTHFR C677T genotype and HPA stress regulation at 6 years of age
Authors: Hookenson Kaia Vivian , Weinberg Joanne , Brain Ursula , Devlin Angela M , Oberlander Tim F 
Published: June 2021

Major depression is often characterized by elevated daily cortisol concentrations reflecting altered hypothalamic pituitary adrenal (HPA) regulation. A dysregulated maternal HPA axis may exert early programming effects on fetal HPA activity. The methylenetetrahydrofolate reductase (MTHFR) gene, an enzyme required for folate metabolism, has a variant (C677T) associated with depression. It remains unknown whether the C677T variant moderates the effect of antenatal maternal depression in shaping HPA function during early childhood. To study if an association between antenatal maternal mood and offspring HPA regulation may be moderated by C677T genotype, salivary cortisol concentrations were obtained from children (n=59) over four days [early morning awakening (mean 7:42 ± 0.91 h), 15 min later (8:02 ± .96 h), and evening (18:40 ± 2.35 h)]. Using a linear regression model, prenatal SRI antidepressant exposure, and maternal mood (Hamilton Depression Rating Scale) at 33 weeks and 6 years, did not predict cortisol concentrations. However, children with 677TT genotype (n=9) had higher evening cortisol concentrations (β=−0.384, P=0.004), and a smaller change from early morning to evening (β=0.292, P=0.037), compared to children with 677CC and CT. These data suggest that children with a MTHFR 677TT genotype have both elevated and altered diurnal cortisol patterns, possibly indicating HPA axis dysregulation.Supported by Canadian Institutes of Health Research, and the Human Early Learning Partnership.
Epidermal growth factor modulates colon epithelial innate immune signaling
Authors: Dubé Philip , Polk D. Brent 
Published: June 2021

Epidermal growth factor (EGF) and its receptor (EGFR) enhance colon epithelial healing through cell migration, proliferation and survival. Since barrier disruption induces epithelial innate immune activation by luminal microbial products, such as lipopolysaccharide (LPS) acting through toll‐like receptor 4 (TLR4), we sought to determine if EGF modulates this response as an additional mechanism to limit inflammatory responses and optimize healing. We hypothesized that EGF inhibits epithelial responses to TLR activation.MethodsMouse colon epithelial cells (YAMC) were used to determine the effect of EGF on TLR expression (qRT‐PCR) and function (NFκB luciferase reporter, CXCL2 mRNA induction, and chemokine secretion by ELISA or multiplex bead array)ResultsEGF suppressed TLR4 and 7 mRNA in a sustained manner without affecting other TLRs. This was specific to epithelial EGFR, and was not observed in macrophages, or in response to other growth factors or cytokines. EGF treatment inhibited colon epithelial NFκB activity in response to LPS and triacylated lipopeptide (TLR1/2 agonist). EGF also reduced LPS‐induced CXCL2 mRNA and secretion of CXCL2, GCSF, LIF, IL‐6 and GM‐CSF. The EGF inhibition of LPS‐induced NFκB activity required the adaptor protein YMER and was abolished by YMER siRNA.DiscussionThese results uncover a novel role for EGF to modulate TLR signaling in colon epithelial cells at the level of expression and function. These effects appeared specific to epithelial cells and required a cytosolic EGFR substrate, YMER. Thus, EGFR modulates epithelial responses to microbial cues and may provide an immunomodulatory signal for the colon epithelium. Since TLR4 transactivates EGFR, this may be a feedback mechanism whereby EGFR activation limits TLR responses. Support by NIH and CCFA.
Selection of candidate genes for hypertension on rat chromosome 4 from shr using expression profilling in kidney and subcongenic strain development
Authors: Teixeira Samantha Kuwada , Rodrigues Mariliza Velho , Morales Marcelo Marcos , Krieger José Eduardo 
Published: June 2021

Using total genome scan, we previously mapped 5 BP‐related QTLs that explain 38% of the BP variance in a progeny derived from Spontaneous Hypertensive Rat (SHR) and Brown Norway (BN) rats. The QTLs were then validated by derivation of congenic strains, including one for chromosome 4 (SHR.BN4) in which a segment from BN replaced the SHR sequences reducing basal systolic BP (~15 mmHg). To select the putative candidate genes, we used genomic approaches based on differential expression in kidney samples and development of subcongenic strains. Sixteen genes were differentially expressed in samples from adult renal tissues from congenic strain SHR.BN4 compared with SHR. Of those, seven remained differentially expressed in the kidney from pre‐hypertensive animals displaying comparable levels of blood pressure. We then verified which of those candidate genes were expressed along the nephron and if they were differentially expressed in mRNA samples from 5 microdissected nephron segments from the two groups. All 7 genes were differentially expressed in one or more of the nephron segments between the 2 strains. Meanwhile, two nonoverlapping congenic substrains were obtained from SHR.BN4, which maintained its phenotype, and one of those harbours 2 of the candidate genes (MGC95152 and Aqp1). Taken together, the combined approaches resulted in selection of 2 hypertensive candidate genes that deserve to be further explored.Supported by FAPESP, CNPq and E.J. Zerbini
AN OVERVIEW OF STUDY METHODOLOGY AND KNOWLEDGE RETENTION IN VETERINARY ANATOMY ON DVM STUDENTS
Authors: Trincado Carlos , Gutierrez J. Claudio , Freeman Larry 
Published: June 2021

Anatomy is considered a cornerstone in medical education. Dissecting anatomical pieces, is the ideal way to learn this subject. However, always there is a limitation, since the access to the anatomy lab and the number of cadavers is restricted. That is why throughout the history of anatomy instructions, other academic tools have emerged such as photographic atlas, new preservation techniques such as plastination, and more recently, the use of computer software technology.The aims of this study were to collect information on the supportive methods used by freshmen DVM students and the quality of knowledge retention in senior students that coursed the Bovine Anatomy class in the Veterinary Sciences College of the Austral University of Chile. The implementation of a survey and a diagnostic exam were used for this purpose.Results showed that the main material used by freshmen students to support their preparation for the Anatomy exams books (38.5%), and that only 12.2 % of the students used some computer technology. Results might be explained by the absence of a complete Anatomy software for the bovine species. Therefore, almost all students (97.8%) agreed with the possibility of having a computer software for complementing the study of Bovine Anatomy. Regarding the diagnostic exam there were only 33.2% of correct answers which represent a low retention of knowledge in senior DVM students.
Differential effects of diet composition and exercise on human hunger and satiation
Authors: Lin Po‐Ju , Borer Katarina 
Published: June 2021

How diet composition and exercise influence human hunger and satiation was examined in a study where exercise (X) or sedentary (S) condition preceded meals of either Paleolithic (P) or Western (W) composition.PURPOSEExamine the effect of P and W meals and X or S on hunger and fullness ratings during postprandial periods (PPs).METHODSPostmenopausal women engaged in 1 of 4 conditions: S or 2 bouts of X (7–9 h and 14–16 h) with P or W meals (PS, PX, WS, WX; n=8 each) provided at 10 h and 17 h. PP hunger and satiation were measured hourly with a 100‐mm visual analog scale. Meals contained 30% carbohydrate (CHO), 25% protein (PRO), and 45% FAT in P vs 60% CHO, 15% PRO, and 25% FAT in W. Changes in hunger and satiation to X, P and W during two PPs were tested with repeated‐measures mixed model ANOVA.RESULTSSatiation during both PPs was unaffected by either P,W or X. Hunger ratings were significantly lower to P meals during both PPs. An additional suppressive effect of exercise during 1st PP, and an interactive effect of X during 2nd PP, was apparent but not statistically significant.CONCLUSIONAbsence of a differential effect of diet composition and exercise on the satiation suggests a role of meal volume in its control. Differential effects of diet, and possibly of exercise, on hunger ratings, suggest a sensitivity in hunger controls to variations in nutrient composition and energy expenditure.
Comparative evaluation of the results of open video endoscopic operations of patients with esophageal achalasia
Authors: Volchkova Irina 
Published: June 2021

The objective of the study was to determine whether results of open and laparoscopic operations for esophageal achalasia are comparable. All patients (n = 53) were divided into two groups according to the used method of oesophagocardiomyotomia: first ‐ basic (laparoscopic) group (n = 29), in which a laparoscopic approach has been used, the second ‐ control (open) group (n = 24), in which open (laparotomy) oesophagocardiomyotomia was used.Blockade was completely (100%) eliminated in cardioesophageal transition using the improved method of oesophagocardiomyotomia year after operation in comparison with a standard method, which had the current indicator in 79.2% of the value of all clinical cases. We observed endoscopically full antireflux effect in 96.6% operated in the first group versus 75% in the comparison group. Endoscopically positive GER was detected in 1 (3.4%) patient of the main and in 6 (25%) patients of the control group ( ƒÔ2=4,9; „Q=0,025). An improved method of laparoscopic oesophagocardiomyotomia is characterized by a more pronounced antireflux effect than laparotomy (96.6% versus 75% respectively) and by 100% removal of the disturbed patency of cardioesophageal transition versus 79.2% of the control group.
Schwann cell transplantation enhances diaphragm recovery following cervical spinal cord injury
Authors: Mercier Lynne , Arias Natalia , Gonzalez‐Rothi Elisa , Little L. Nicole , Fuller David , Muir Elizabeth , Rogers John , Bunge Mary , Lane Michael , Reier Paul 
Published: June 2021

Respiratory function is compromised following cervical spinal cord injuries (cSCI) due to interruption of respiratory pathways. Peripheral nerve grafts, a source of Schwann cells (SCs), alone or in combination with other treatments have been reported to promote improved respiration after cervical hemisection. SC transplantation in a contusion model has shown to improve locomotor function. In this study, we looked at how SCs would affect respiration in a clinically‐relevant contusion cSCI model.Adult female rats received lateralized C3/C4 contusion cSCI, leading to a rapid shallow breathing pattern (RSB). At 1 week post‐injury, animals were injected into the lesion site with SCs (~2.5 million) expressing either mCherry or green fluorescent protein (gfp). Controls were lesioned only. Animals receiving SCs were immunosuppressed. Respiratory function under eupneic and hypercapnic conditions was assessed. Histological analyses confirmed survival of SCs. Our initial findings show that RSB was absent in SC recipients, which also had improvement in diaphragm EMG activity during hypercapnia. Preliminary results with grafts of SCs expressing Chondroitinase ABC did not have any additional effect. These preliminary results suggest SCs can alone promote recovery after experimental cSCI. Identifying substrates mediating this recovery and how brainstem plasticity is affected also are under investigation.
miR‐21 Knockdown Attenuates the Cardioprotective Effects of Isoflurane
Authors: Olson Jessica , Yan Yasheng , Kriegel Alison , Bai Xiaowen , Liang Mingyu , Bosnjak Zeljko J. 
Published: June 2021

Anesthetic‐mediated cardioprotection has been shown to decrease myocardial infarct size after ischemia‐reperfusion injury. Many cell signaling pathways have been investigated in this phenomenon, however, the role of microRNA remains unknown. MicroRNAs are short, non‐coding nucleotide sequences that negatively regulate gene expression through degradation or suppression of messenger RNA. Previously, we have shown that miR‐21 is upregulated approximately 2.5‐fold after exposure to isoflurane in both in vivo and in vitro rat models. In this study, we investigated the effect of knocking down miR‐21 expression on cardioprotection by isoflurane in neonatal rat cardiomyocytes.Knockdown of miR‐21 in neonatal rat cardiomyocytes was achieved by transfection with Lipofectamine and confirmed using qRT‐PCR. Lactate dehydrogenase release assays were conducted to assess cell viability compared to scramble‐transfected controls. Our results show that miR‐21 knockdown attenuates the cardioprotective effect of isoflurane in neonatal rat cardiomyocytes. We have also shown a correlation between miR‐21 knockdown and decreased expression of pAkt, a well‐established mediator of protective cell signaling pathways. Further investigation into the mechanisms by which miR‐21 contributes to cardioprotection may offer novel insight into the attenuation of ischemia‐reperfusion injury.
Changes in Body Composition with Six Weeks of Resistance Training
Authors: Chen Vincent C.W. , Lee Chang Woock , Lee Teak V. , Bui Steve , Fluckey James D. , Riechman Steven E. 
Published: June 2021

PurposeResistance exercise training has been shown to increase muscle mass. However, it is not as common to be recommended for fat loss. The purpose of this study was to examine the effects of 6‐week resistance exercise training on body composition.MethodEight untrained young men and women (Age=24±5, BMI=30±3) performed a 6‐week progressive whole body resistance training program, consisting of chest press, leg press, lat pull‐down, leg curl, arm curl, leg extension and triceps extension. Dual‐energy X‐ray absorptiometry (DEXA) was performed before and after training.ResultsAfter 6 weeks of resistance exercise training, lean mass significantly increased by 2.06±0.95% (54.55±3.03 to 55.8±3.39 kg, p=0.040), while body fat percentage significantly decreased by 5.05±1.33% (29.85±5.90 to 28.58±5.85 kg, p=0.013). There was no significant change in total body mass (87.66±6.64 to 87.63±6.64 kg, p=0.941).ConclusionSix weeks of resistance exercise training is sufficient to result in significant muscle gain and fat loss. While total body mass remained unchanged, body composition was improved. Therefore, resistance exercise may be recommended for the purpose of fat loss while improving muscle mass.
Effect of Hypoxic Training on Fatty Acid Oxcidation in Obese Rats
Authors: Feng lianshi , Lu yingli , Zhang li , Xu jianfang , He zihong 
Published: June 2021

ObjectiveTo study the effects of hypoxic training on fatty acid oxcidation of obese rats.Method130 obese rats were divided into 13 groups at random:control group, normoxic training 1,2,3,4 week group, hypoxia sedentary1,2,3,4 week group, and hypoxic training 1,2,3,4 week group. The rats in training groups ran on a treadmill for 60 min a day at 26 m/min in normoxia or 21 m/min in hypoxia(13.6%), 6 days a week for 1–4 weeks. After corresponding week, Real‐time quantitative PCR was adopted to test the expression of carnitine palmitoyl transferase (CPT‐1mRNA) in gastrocnemius and liver. Lipoprotein lipase in gastrocnemius (LPLm) and adipose (LPLa) were measured using ELISA.Results1)Hypoxic training 4 week significantly reduced CPT‐1mRNA in liver more than control, and even more than normoxic training (P<0.05) ;2) CPT‐1mRNA in gastrocnemius of obese rats was increased in 3–4 week (P>;0.05), and in 4th week, CPT‐1mRNA was significantly higher in hypoxic training group compared with normoxic training and hypoxia sedentary (P< 0.05) ;3) After 4 weeks, LPLa/ LPLm was lower in hypoxic training group than normoxic training group (P<0.05).Conclusion1)Hypoxic training increased fatty acid oxcidation of skeletal muscle more than normoxic training. 2)Hypoxic training decreased fatty acid oxcidation of liver and even more than normoxic training.(Supported by NSFC: Grant No. 30971415)