bluuebunny/crossref_metadata_2025 huggingface dataset:
Beneficial Effects of Nrf2 Activation on Vascular Function and Detrimental Effects of Nrf2 Activation on Renal Function in Dahl Salt‐Sensitive Rats
Authors: Lombard Julian H. , Fink Katie , Cloutier Dustin , Bukowy John , Kozak Kaleigh , McCord Joe
Published: June 2021

The master antioxidant and cell protective transcription factor nuclear factor (erythroid‐derived 2)‐like‐2 (Nrf2) plays a key role in maintaining redox homeostasis by binding to antioxidant response elements (ARE) in the promoter regions of multiple antioxidant genes. The goal of these experiments was to determine whether direct activation of Nrf2‐mediated antioxidant defenses with Protandim (~40 mg/m2 per day for 2 weeks): 1) ameliorates endothelial dysfunction and oxidative stress in cerebral arteries of Dahl salt‐sensitive (SS) rats fed high salt (HS; 4% NaCl) diet; 2) improves renal function; and 3), increases skeletal muscle microvessel density in HS‐fed SS rats. Protandim treatment restored endothelium‐dependent vasodilation in response to acetylcholine (ACh) in the middle cerebral artery (MCA) of SS rats fed HS diet, but failed to increase skeletal muscle microvessel density or improve glomerular injury scores. Nrf2 activation also led to elevated urinary albumin levels and increased protein casting in renal tubules of HS‐fed SS rats. Protandim downregulated the expression of the pro‐oxidative transcription factor Kruppel‐like factor 9 (Klf9) in cerebral arteries but upregulated Klf9 expression in kidneys of HS‐fed SS rats fed HS diet. These findings support the hypothesis that pharmacological activation of Nrf2 during high and sustained levels of oxidative stress can have either beneficial effects (cerebral arteries) or detrimental effects that may be mediated by upregulation of Klf9 (kidney). These differential effects could have contributed to the failure of the BEACON clinical trial involving Nrf2 activation in patients with type 2 diabetes and advanced (stage 4) kidney disease; and may provide safety guidelines for therapeutic administration of Nrf2 activators in conditions characterized by elevated oxidative stress.

Support or Funding Information

NIH #R01‐HL128242 and #R21‐OD018309‐JHL

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Effect of Shikonin on Cardiac Wound Healing in Mice
Authors: Cai Ashley , Cai Zheqing
Published: June 2021

Shikonin has been shown to have properties of improving open wound healing, but it is not known whether shikonin is effective in promoting cardiac repair after myocardial infarction (MI). We hypothesize that shikonin can improve wound healing in infarcted hearts. We created MI models by ligating the coronary artery in mice. We treated the infarcted mice with 5 mg/kg of shikonin a day through oral gavage, or the same volume of distilled water was given to the control group. After seven days of treatment, we documented the heart weight and body weight, and the hearts were photographed and the infarct size was measured. The ratio of heart weight to body weight was calculated.

We found that the infarct area in treated mice was significantly smaller than in the control group. While there was no significant difference in body weight between the two groups, but the ratio of heart weight to body weight in the treated group was much smaller than in the control group. In conclusion, shikonin was effective in helping wound healing in the heart after MI. Future studies will be directed to further study how shikonin functions at the cellular level and whether it improves cardiac function.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
DOC2B enhanced muscle insulin sensitivity by interacting with cytoskeletal proteins
Authors: Zhang Jing
Published: June 2021

Strategy to enhance skeletal muscle insulin sensitivity is a primary way to substantially reduce the risk of diabetes. Evidences have shown that whole‐body DOC2B over‐expressing mice have enhanced peripheral insulin sensitivity. However, the level of contribution of skeletal muscle specific DOC2B accounting for this enhancement and the underlying mechanism remain unclear. Towards this, we generated a new tetracycline/doxycycline (DOX)‐inducible skeletal muscle specific DOC2B over‐expressing mouse model and demonstrated that the DOC2B enrichment in skeletal muscle is sufficient to enhance peripheral insulin sensitivity as well as whole‐body glucose tolerance. Inaddition, DOC2B overexpressing mice exhibited an increase in insulin‐stimulated GLUT4 accumulation at the plasma membrane and this effect of DOC2B overexpression on promoting insulin stimulated GLUT4 translocation was further confirmed in L6 skeletal muscle cells. Importantly, DOC2B overexpression was sufficient to restore GLUT4 translocation in cells rendered insulin resistant. Proteomic analyses and co‐immunoprecipitation indicate that DOC2B interacts with cytoskeletal proteins. We also found that insulin stimulation phosphorylates DOC2B, which enhances the binding of DOC2B to cytoskeletal proteins to promote GLUT4 translocation and glucose uptake. These results support DOC2B as a potential drug target to restore insulin sensitivity in pre‐diabetic and type 2 diabetic individuals.

Support or Funding Information

This work was supported by grants from the NIH/NIDDK (R01 DK067912; R01 DK102233, to Dr. Debbie Thurmond and the American Heart Association (17POST33661194) to Dr. Jing Zhang. Additional financial support was provided to Dr. Debbie Thurmond.: the Ruth and Robert Lanman Endowment, the George Schaeffer award, and an Excellence award, through the City of Hope.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Elevated PBMC‐derived oxidative stress in healthy young African American women
Authors: Johnson Auburn L. , Vranish Jennifer R. , Kaur Jasdeep , Liu Xian , Blankenship Jeanette K. , Pan Zui , Fadel Paul J.
Published: June 2021

Several studies have demonstrated that African Americans (AA) exhibit elevations in systemic oxidative stress compared to Caucasian Americans (CA). Peripheral blood mononuclear cells (PBMCs) have been identified as one of the primary contributors to systemic reactive oxygen species (i.e. oxidative stress) and may be an underlying mechanism for the development of hypertension and cardiovascular diseases. Previous work demonstrates that young healthy AA men have elevated PBMC‐derived superoxide production when compared to CA men. However, whether PBMC‐derived superoxide production is also elevated in young healthy AA women remains unknown. This is important because AA women are also more likely to develop hypertension and cardiovascular diseases than women of any other race. Accordingly, this study investigated PBMC‐derived superoxide production in young healthy AA and CA women. We tested the hypothesis that, relative to CA women, AA women would exhibit greater levels of PBMC‐derived oxidative stress. In ten normotensive AA women and ten age‐matched normotensive CA women, resting intracellular superoxide levels were assessed from freshly isolated PBMCs using dihydroethidium fluorescence. Subjects arrived to the lab following an overnight fast. Resting blood pressure was measured following a 10‐minute rest period and a 50‐mL venous blood sample was then drawn. PBMCs were isolated from whole blood using density gradient centrifugation and intracellular superoxide was assessed using dihydroethidium fluorescence. Resting mean arterial pressure was similar between groups (AA 82.9±1.7 vs. CA 79.4±2.4 mmHg; P =0.26) however the resting intracellular superoxide production was elevated in AA women compared to CA (AA 4.1±1.9 vs. CA 2.7±1.0 Relative Fluorescent Units; P=0.025). These preliminary findings suggest that young AA women exhibit greater resting PBMC‐derived superoxide production. Thus, PBMCs may represent a source of elevated oxidative stress in AA women.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Blockade of glutamate receptors abolishes the sensitization of the angiotensin II‐elicited hypertensive response in rats
Authors: Xue Baojian , Beltz Terry G. , Guo Fang , Johnson Alan Kim
Published: June 2021

Angiotensin (ANG) II‐elicited hypertension is associated with neuroplasticity of glutamate receptors (GluRs) in the brain nuclei involved in blood pressure regulation including the lamina terminalis (LT) and hypothalamic paraventricular nucleus (PVN). Using the Induction‐Delay‐Expression (IND‐DEL‐EXP) experimental paradigm, our previous studies demonstrated that administration of a subpressor dose of angiotensin (ANG) II (10 ng/kg/min) during IND sensitizes subsequent ANG II (120 ng/kg/min)‐elicited hypertension during EXP. This subpressor dose of ANG II also induced increased phosphorylation of the GluN1 subunit in LT structures. The present study investigated whether the blockade of GluRs during IND abolishes sensitization of subsequent ANG II‐elicited hypertension. We found in the rat that the sensitized ANG II hypertensive response produced by a subpressor of dose ANG II given during IND was blocked by co‐administration of either MK‐801 (sc) or of (2R)‐amino‐5‐phosphonovaleric acid (a.k.a. AP5, icv). Moreover, ANG II‐induced upregulation of mRNA expression of several renin‐angiotensin system (RAS) and proinflammatory components in the LT and PVN was also attenuated. These results indicate that central nervous system (CNS) neuroplasticity associated with hypertension response sensitization requires NMDA‐R activation. Furthermore, the inhibitory effect of NMDA‐R blockade on hypertension response sensitization is associated with reducing upregulation of prohypertensive components of the brain RAS and of inflammatory mediators in the CNS.

Support or Funding Information

the National Institutes of Health grants HL‐14388, HL‐84207 and HL‐98207.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Evidence that Zinc Deficiency Impairs Gut Epithelial Barrier and intestinal Immunity
Authors: Sarkar Paramita , Saha Tultul , Aoun Joydeep , Chakraborty Subhra Hoque , Chakrabarti Manoj K. , Dutta Shanta K. , Hoque Kazi Mirajul
Published: June 2021

There is growing interest in dietary factors, in particular micronutrients, from the perspective of disease pathogenesis and potential for treatment. Diarrheal disease in infant results in abnormally low concentrations of serum zinc. Zinc has been tested for its ability to treat and prevent diarrheal diseases in many large field trials over a period of over 4 decades and has generally been found effective. The mechanism by which zinc deficiency causes diarrhea is not known. The present study investigated the impact of zinc deficiency on the host, particularly of intestinal tight junction (TJ) integrity and proteins that are involved in intestinal absorption and secretion along with the pathogenesis of enteric infection. We have used human colonic T84 cells to study barrier function and Shigella to test susceptibility of intestinal infection due to zinc deficiency. T84 grown onto transwell inserts in zinc deficient media showed a low transepithelial electrical resistance (TEER) compare to zinc sufficient media (1014 ± 165 Ω.cm2 vs 3663 ± 293 Ω.cm2) in confluent T84 monolayers. We furthermore analysed the correlation between TEER and paracellular ionic conductance. We found that zinc deficiency altered paracellular ionic conductance. Bacterial transmigration studies showed a significant increase in apico‐basolateral transmigration of Shigella (6.58 ± 0.13 vs 7.98 ± 0.23 log10 CFU/ml) which peaked at 6hrs post infection. Transmission electron microscopy data showed widened TJ complex due to few membrane fusion proteins and distorted TJ morphology, whereas the desmosomes were still intact. Electrophysiological studies with Ussing chamber and qPCR quantification demonstrated reduced cAMP dependent electrogenic Cl− secretion (34.5 ± 1.25 μA/cm2 vs 17.75 ± 2.3 μA/cm2) along with reduced expression of CFTR in zinc deficient cells, resulting dehydrated lumen thus aiding in bacterial colonization. Our results suggest that zinc deficiency caused (1) perturbed barrier function and integrity (2) altered Cl− secretion leading to susceptibility of infection. We conclude that adequate zinc is required to maintain intestinal barrier health to avoid risk against intestinal infection.

Support or Funding Information

Govt of India National Funding Agency

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Na+ transporters, electrolyte excretion and renal injury in female and male C57Bl/6 and IL17A−/− mice during AngII hypertension
Authors: McFarlin Brandon E. , McDonough Jillian C. , Ralph Donna Lee , Veiras Luciana C. , Madhur Meena S. , McDonough Alicia A.
Published: June 2021

Experimental AngII hypertension is reported to be blunted in female (F) vs. male (M) mice and in mice lacking the inflammatory cytokine IL17A (time point dependent). This study aimed to determine how sex impacts renal Na+ transporters, Na+ and K+ excretion, and markers of renal injury during AngII hypertension (A) in both C57Bl/6 (WT) and IL17A−/− (IL17−/−) mice.

11–16 wk old F and M mice were infused with AngII (490 ng/kg/min) or sham treated for 3 wk (n=6/group). Rate of excretion of a saline load (10% b.wt. subcutaneous) was slowed in all AngII infused groups, indicating Na+ reabsorption activation. Blood pressure (BP), by tail cuff, increased similarly across groups (in Δ mmHg): WTMA: 40 ± 1.6, WTFA: 37 ± 10, IL17−/−MA: 37 ± 3.8, IL17−/−FA: 46.4 ± 4.7. Thus, no blunting of hypertension was detected at 3 wk time point by tail cuff in F or in IL17−/−.

In both M and F WT and IL17−/−, AngII provoked activation (‐phosphorylation) of NKCC2 and NCC, and activation of ENaC (more ‐cleaved (Cl), less full length (FL)). These distal anti‐natriuretic responses were balanced by natriuretic responses including: decreased abundance of proximal NHE3, NaPi2, and decreased medullary thick ascending limb NHE3, NKCC2 and NaK‐ATPase (see Figure). We previously proposed that increased ‐NCCp is a secondary compensation, driven by AngII activation of ENaC, to minimize K+ secretion (PMID27600183). Providing further support for this idea, urinary Na/K ratio (UNa/K), collected overnight (during fasting +water), was significantly reduced by AngII (WTM: from 0.71 ± 0.1 at baseline to 0.41 ± 0.9 with AngII, WTF: 0.80 ± 0.1 to 0.28 ±0.05, IL17−/−M: 0.99 ±0.13 to 0.41 ± 0.041, IL17−/−F: 1.05 ± 0.07 to 0.46 ± 0.46). UNa/K fell due to decreased o/n UNa as o/n UK was unaltered by AngII. Urine volume (V), unaltered by AngII treatment, was 2‐fold higher in M vs. F of both genotypes, and 2‐fold higher in IL17−/− vs. WT within each sex.

During AngII, the injury marker U albumin increased across groups. Renal cortical angiotensinogen was lower in IL17−/− vs. WT (by 50% in F and 25% in M). KIM1 also tended to be lower in IL17−/− vs. WT in both sexes during AngII.

From these results, we propose: AngII stimulation of ENaC drives UK secretion which activates NCCp (more in WT than IL17−/− males), thus reducing UNa to limit K secretion and lowering UNa/K which may contribute to BP elevation. IL17−/− mice exhibit higher UV and lower intrarenal angiotensinogen and KIM1 which suggests less tissue injury.

Support or Funding Information

AHA GIA (15GRNT23160003) and an NIH NIDDK R01 (DK083785) to A.A. McDonough, NIH NHLBI K08 award (HL121671), Gilead Cardiovascular Scholars Grant, and NIH DP2 award (HL137166) to M.S. Madhur

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
MicroRNA‐146a Deficiency Promotes Atherosclerosis by Dysregulating Cholesterol Homeostasis in Macrophages
Authors: Chen Li‐Jing , Huang Yi‐Hsuan , Shih Ting‐Ying , Chien Shu , Chiu Jeng‐Jiann
Published: June 2021

Atherosclerosis is a chronic inflammatory disease that results from imbalance of high‐density lipoprotein (HDL) cholesterol metabolism and a maladaptive immune response driven by the accumulation of cholesterol‐laden macrophages in the artery wall. MicroRNA‐146a (miR‐146a) serves as anti‐inflammatory function in a variety of cell types, but the underlying mechanisms of miR‐146a in atherosclerosis still remain unclear. In the present study, we assessed the impact of the genetic deficiency of miR‐146a in a mouse model of atherosclerosis and determined the miR‐146a‐mediated balance of cholesterol metabolism in macrophages. In comparison with miR‐146a+/+ApoE−/− mice fed with high‐cholesterol diet for 10 weeks, miR‐146a−/−ApoE−/− mice showed an increase number and area of atherosclerotic plaques, lipid content, pro‐inflammatory cytokines and abundant macrophages accumulated in the plaques. In addition, miR‐146a−/−ApoE−/− mice also showed decrease in HDL levels. Bone marrow chimera experiments indicated a major effect of miR‐146a deficiency on lesional macrophages. Bone marrow derived‐macrophages (BMDMs) were isolated from miR‐146a−/−ApoE−/− and miR‐146a+/+ApoE−/− mice to stimulated with oxidized low‐density lipoprotein (oxLDL). In comparison with BMDMs of miR‐146a+/+ApoE−/−, BMDMs of miR‐146a−/−ApoE−/− showed a significant oxLDL uptake and reduction in cholesterol efflux capacity. The expression of cholesterol transporters, including the ATP‐binding cassette sub‐family A1 (ABCA1) and sub‐family G1 (ABCG1) were significantly decreased in BMDMs of miR‐146a−/−ApoE−/−. By using the global gene expression analysis and argonaute‐2 immunoprecipitation, we demonstrated that toll‐like receptor 4 (TLR4) is directly targeted by miR‐146a. Overexpression of miR‐146a and silence of TLR4 not only increased the expression of ABCA1 and ABCG1, but also increased the cholesterol efflux capacity and reduced the oxidized LDL uptake. These data demonstrated that miR‐146a is involved in regulation of ABCA1 and ABCG1 by targeting TLR4, and that maintains the balance of HDL cholesterol metabolism to protect against the atherosclerosis. MiR‐146a is a potential target in treatment of atherosclerotic vascular disease.

Support or Funding Information

MOST 104‐2321‐B‐400‐020‐MY3 (to L.‐J. C.) and MOST 104‐2321‐B‐400‐017 (to J.‐J. C.).

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
AMP‐activated protein kinase in muscle is essential in ketone body utilization
Authors: Bedarida Tatiana , Han Young‐Min , Wu Yue , Liu Zhaoyu , Song Ping , Zou Ming‐Hui
Published: June 2021

Background

Starvation leads to a series of metabolic adaptations that enables continuous production and delivery of nutrients to critical organs, tissues and cells. Under conditions of nutrient withdrawal, ketone bodies provide an alternative source of energy for highly oxidative tissues. Although the AMP‐activated protein kinase (AMPK) is best known as a sensor of cellular energy status, its implication in ketone regulation remains unclear.

Objective

The aim of this study was to evaluate the effects of AMPKα2 on ketone body utilization, and to elucidate the underlying mechanisms.

Methods

Global AMPKα2 knockout mice (AMPKα2−/−), muscle‐specific AMPKα2 knockout mice, and their age‐matched wild type (WT) littermates were subjected to either 3‐day fasting or received an intra‐peritoneal injection of β‐hydroxybutyrate salt (1.5 mg/kg body weight) to assess the β‐hydroxybutyrate consumption.

Results

Fasting blood and urine ketone levels were significantly elevated in AMPKα2−/− mice when compared to their littermate WT mice. After an intra‐peritoneal bolus of β‐hydroxybutyrate, the main circulating ketone body, AMPKα2−/− mice presented a lower clearance of β‐hydroxybutyrate compared to their littermate WT mice. Further, fasting induced hyperketosis without any change in body weight or glycaemia in muscle‐specific AMPKα2 knockout mice. Consistently, these mice displayed impaired ketone utilization after β‐hydroxybutyrate injection. Furthermore, AMPKα2 deficiency in muscle significantly decreased locomotor activity, with a quicker switch from utilizing carbohydrate to fat as the predominant energy source compared to their littermate WT mice. Mechanistically, AMPKα2 deficiency in muscle presented a 50% reduced activity of succinyl‐CoA:3‐oxoacid CoA transferase compared to their littermate WT mice.

Conclusion

Taken together, these findings establish AMPKα2 in muscle as an essential mediator of ketolysis in fasting, through the regulation of the rate‐limiting ketolytic enzyme.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Testosterone Supplementation Does Not Affect Skeletal Muscle Growth When Administered Alone in Either Sex and Requires an Additional Anabolic Stimulus to Exert Its Effects in Female Mice
Authors: Davidyan Arik , Baar Keith , Bodine Sue C.
Published: June 2021

Testosterone (T), the main androgenic hormone, is thought to positively affect skeletal muscle mass and function. The anabolic effects of T have been attributed to its effects on satellite cell proliferation and differentiation as well as its activation of pathways downstream of the IGF‐1 receptor and AKT. The role of T activity in skeletal muscle health and growth however remains equivocal, with some studies showing T to have great importance in muscle hypertrophy, while others suggest a limited role or no significant effect. Considering the increased use of chemical castration as a treatment for prostate cancer, and the growing use of testosterone in the elderly population, there is a growing need to establish T's role on skeletal muscle in relation to sex and age. Therefore, the aim of this project is to delineate molecular pathways that are affected by T as well as the phenotypic outcome of T treatment in skeletal muscle.

The effects of supra‐physiological levels of T, in the form of subcutaneously implanted slow‐release T pellets, on muscle mass and strength were determined in 5‐month‐old male and female C57Bl6 mice. Mice were subjected to 3‐weeks of treatment and analyzed for muscle mass, plantar‐flexor strength, protein synthesis and degradation, and mTORC activity. Under free living conditions, T supplementation has no effect on mass of the TA, gastrocnemius, or quadriceps muscles in either sex; nor did it result in a gain in ankle extensor torque. In addition, T supplementation resulted in no significant changes in proteasome activity or whole muscle protein synthesis.

To determine whether T has a greater effect on skeletal muscle mass when combined with increased load, we utilized the functional overload (FO) model, removing both the gastrocnemius and soleus muscles, in both sexes. Female mice that underwent FO and were supplemented with T for two weeks showed 94.6% ± 12.2% greater hypertrophy in the plantaris muscle compared to those that were not supplemented. However, in male mice T supplementation in addition to FO failed to significantly increase the plantaris mass when compared to those that only underwent FO. Fiber cross sectional area analysis of the investigated muscles compliments these phenotypic results. Together these data suggest that an additional and concurrent stimulus may be required for T to exert an anabolic effect in skeletal muscle of female mice. Additionally, T supplementation to male mice does not provide a beneficial effect when administered alone or together with increased load.

Support or Funding Information

UC Davis Clinical and Translational Science Center

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Expression of muscle mTOR mRNA in relation to changes in food intake in channel catfish
Authors: Spainhour Rebekah , Abernathy Oaklee , Dougherty Megan , Schmidtberger Abigail , Kostner Danica , Kobayashi Yasuhiro
Published: June 2021

Objectives of this study were to examine the relationship between expression of mechanistic target of rapamycin (mTOR) mRNA and increased food intake in the muscle of channel catfish. mTOR plays a key role in the regulation of protein synthesis, cell growth, cell proliferation, and nutrient metabolism. In our previous study, we characterized tissue distribution of mTOR mRNA and changes in its expression in response to prolonged fasting and showed that fasting increased the expression of mTOR mRNA in muscle of channel catfish. Given that genetic selection towards growth causes the development of obese‐like phenotype in channel catfish, it is possible that increased food intake affects the expression of mTOR mRNA in muscle. Therefore, the relationship between muscle expression of mTOR mRNA and increased feeding frequency was examined in our current study. Juvenile channel catfish were fed at every 12, 24, or 48 hours for 28 days (n=4 tanks per treatment, 8 fish per tank). Muscle expression of mTOR mRNA was measured using quantitative RT‐PCR from the samples collected at the end of the 28‐day feeding period. Muscle expression of mTOR mRNA was significantly greater in fish fed every 48 hours compared to those fed every 24 hours (p<0.05). In contrast, the expression of mTOR mRNA was similar between fish fed every 24 hours and those fed every 12 hours. Our results suggest that the expression of mTOR mRNA in muscle is sensitive to nutritional stress, which is similar to observations made in mammals.

Support or Funding Information

This study is supported by the Kansas IDeA Network of Biomedical Research Excellence.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Exercise characteristics in manganese superoxide dismutase overexpressing mice
Authors: Gaillard Charleston E. , Rao Shriya D. , Klatt Benjamin T. , McKinley Alexander J. , Shanely R. Andrew , Christian Brooke E. , Zwetsloot Kevin A.
Published: June 2021

Oxidative stress, the production of free radicals and reactive oxygen species, can be a result of prolonged and high intensity exercise and may lead to skeletal muscle fatigue and dysfunction, and decreased exercise performance. Manganese superoxide dismutase (MnSOD), a naturally existing mitochondrial antioxidant enzyme, provides the first line of defense against oxidative stress caused by superoxide anions. Transgenic mice overexpressing MnSOD have been studied within the context of disease pathology, but skeletal muscle function and exercise capacity in these mice have not been characterized. Therefore, the objective of this study was to investigate if grip strength, maximal exercise capacity, and exercise endurance differ between transgenic mice that overexpress MnSOD in the mitochondrial matrix (SOD2) and their wild‐type (WT) littermates. Female SOD2 and WT mice (8–10 mo old) performed 3 consecutive forelimb grip strength tests, with 1‐min rest between trials. Next, these mice performed a maximal exercise capacity test, which consisted of a 10‐min warm up at 10–12.5 m•min−1 and 5–10° incline, followed by 2‐min stages of increasing treadmill speed by 3 m•min−1 every stage; treadmill remained at 10° incline and mice ran to exhaustion. Then, 48 hours after the completion of the maximal exercise capacity test, all mice performed an exercise endurance test, consisting of a 10‐min warm up at 10–12.5 m•min−1 and 5–10° incline, followed by a run to exhaustion at a constant treadmill speed of 22 m•min−1 and incline of 10°. Grip strength, maximal exercise capacity, and exercise endurance were not different between SOD2 and WT mice, respectively (p>0.05, all). These findings suggest that overexpression of MnSOD in the mitochondrial matrix does not alter grip strength, treadmill exercise capacity, or endurance in mice.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Flipped Classroom Narrows the Performance Gap Between Low and High Performing Students
Authors: Thor Der , Zheng Meixun , Xiao Nan
Published: June 2021

The flipped classroom has been shown to have positive outcomes in learning and has begun to emerge in medical and dental education. However, there is little information on the impact of the flipped method on learning for high performing students compared to low performing students. In this study, two consecutive classes of students in their first year of the three‐year Doctor of Dental Surgery program at the Arthur A. Dugoni School of Dentistry, University of the Pacific, was taught the physiology of the autonomic nervous system (ANS) through either a traditional lecture method (first class) or using a flipped classroom approach (second class). Students' understanding of the ANS was evaluated using a multiple choice question quiz. In agreement with previous studies, students learning through the flipped approach achieved significantly higher scores than students learning through the traditional lecture method. While students in the lower 27% and higher 27% of the class both showed significantly higher average scores using the flipped approach, the improvement was significantly higher in students from the lower 27%. Our study suggests that the flipped classroom can be used to improve student learning and narrowed the performance gap between low and high performing students.

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 Impact of a Team Based Learning Exercise in the Understanding and Retention of Medical School Nutrition Education
Authors: Cialdella‐Kam Lynn , Khadilkar Surya
Published: June 2021

Background

Integration of clinical nutrition into medical school curriculum is essential in order to produce future physicians who are knowledgeable and confident in applying nutrition as it relates to disease prevention and treatment of disease. Currently, limited curriculum time is dedicated to nutritional content and many medical students lack confidence in applying their nutritional knowledge to a clinical context. A team‐based learning exercise (TBL) was implemented in the Case Western Reserve School of Medicine (CWRU SOM) curriculum during the preclinical nutrition, gastroenterology and biochemistry block in order to enhance and increase nutritional knowledge and confidence. We believe that a TBL is an effective modality to educate students on the fundamentals of nutrition and increase retention of this information.

Key Message

The objective of this study is to determine if the implementation of a TBL activity will enhance medical students' understanding of nutrition concepts and increase retention of nutritional information during the clinical years. At CWRU SOM, we have received personal feedback from students wishing that they had more exposure to nutrition concepts during their preclinical years. Literature reviews have also demonstrated that many medical students lack confidence in demonstrating their nutritional knowledge in a clinical context, including during their clinical rotations. We believe that increasing the amount of nutrition content students are exposed to during their preclinical years would ultimately help increase students' knowledge and confidence. The TBL exercise was implemented into the required preclinical curriculum for first year medical students. For preparation, students were asked to watch a series of short videos focusing on specific nutrition concepts such as metabolic syndrome, hypertension, and nutrition labels. The TBL exercise focused on case vignettes which applied the information introduced in the videos. In order to evaluate the efficacy of the team‐based learning session, an optional posttest was administered both to students who received the intervention and to a randomly selected medical student cohort that did not participate in the educational intervention, and their results were compared.

Discussion

A lack of basic understanding and confidence in nutritional counseling motivated us to seek out a new opportunity to incorporate more nutritional content into the preclinical curriculum. Incorporating additional nutrition content to the preclinical curriculum is not only responsive to previous feedback, but provides an opportunity to improve students' understanding of nutrition as it relates to disease prevention and treatment of disease.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Embedding Three Styles of Interviews into a Senior Seminar Course Provides Students with Practice, Assessment of Skills and Improves Confidence
Authors: Halpin Patricia A. , Landon Jennifer
Published: June 2021

Preparing science undergraduates for success after graduation involves more than teaching them the standard curriculum and laboratory skills. The purpose of this intervention was to prepare undergraduates for their first job/graduate school/professional school interview. Senior Seminar (BSCI 701) is a required course for all science majors that is taken during the first or second semester of a student's final year of college. Three different styles of interviews were assigned to students: A synchronous simulation software (Interview Stream) interview, an in‐class mock interview, a videotaped interview at the Internship and Career Planning office conducted by Internship and Career Planning staff. This intervention was performed during the fall semester of 2015 (n=11) and 2016 (n=12). Students were surveyed at the beginning and of end the semester and the results of both sections were combined. Overall students' confidence increased as 47.6% of the students reported they were very confident with their interview skills at the beginning of the semester compared to 65.2% at the end of the semester. After completing the synchronous simulation video interview, some students reported they felt uncomfortable speaking into the camera, yet they saw value in the ability to identify some of their nervous habits during the playbacks. Performing the in‐class mock interview with a classmate, students reported they felt more comfortable, confident and they appreciated feedback from a peer. After reviewing their videotaped interview with an Internship and Career Planning staff member, they learned they need to make eye contact, smile, speak clearly, have good posture, and wear professional dress. At the end of the semester, students reflected on the skills that they can improve upon and these include: warm up to the interviewer more quickly, think before answering quickly, rehearse answers to common questions, avoid fidgeting, avoid lengthy pauses, make eye contact and overall, being less nervous. By providing students with a variety of opportunities to practice their interview skills, they will feel more confident and be aware of how they can improve. The more practice and feedback they receive will make them more successful presenting themselves professionally post‐graduation.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Maternal exposure to Bisphenol‐A Induces Epigenetic Changes in metabolic syndrome markers of Offspring
Authors: Memon Samreen , Bano Umbreen , Shahani Muhammad Yaqoob
Published: June 2021

Environmental factors exert significant effects of on disease progression later in the life, when exposed in‐utero. Bisphenol A (BPA) is a monomer of plastic products widely used in everyday life. BPA shows hormone mimicking properties, and its adverse effects on endocrine glands and hormones may affect developmental embryology of offspring. Bisphenol A may possibly have an epigenetic role in onset and progression of several adult diseases related to metabolic system. To determine the epigenetic effects of in‐utero Bisphenol A on markers related to metabolic syndrome in mice offspring. This study was conducted at department of Anatomy Liaquat University of Medical & Health Sciences Jamshoro and Animal house of Sindh Agriculture University Tando Jam Pakistan after Ethical approval. Adult female BALB/c strains mice were divided in three groups each comprised of 10 female mice– G1 (controls), G2 (ethanol 0.10 ml i.p) and G3 (BPA 10 mg i.p). Animals were housed individually in polypropylene cages, in standard lighting, controlled temperature and humidity conditions. Control group was fed ad libitum. After mating, the positive vaginal plug was checked to confirm pregnancy. Offspring body weight, behavior, movement, blood glucose; serum insulin, cholesterol and HDLc were measured at 5 months age and at 15 months age before sacrifice of animals. Pancreas, kidney, adipose tissue and uterine tissue were stained with H & E staining and Immunohistochemistry and examined under microscopy. Data was analyzed on SPSS 22.0 (at 95% confidence interval). Offspring of group G3 reveals abnormal changes in behavior and movement. Body weight, blood glucose, serum insulin, cholesterol and HDLc were high compared to controls (P=0.0001). Islets of Lanherghan's, Kidney and Uterine tissue reveals abnormal anatomical changes with anti‐ Islet‐1 Ig, Ksp cadherin, and anti‐ MLH antibody respectively. In utero exposure of endocrine disruptor Bisphenol A exerts Diabetogenic and Atherogenic effects with abnormal immunohistochemistry changes in endocrine pancreas, kidney and uterus.

Support or Funding Information

This study was funded by Liaquat University of Medical & Health Sciences, Jamshoro, Pakistan

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Impact of housing temperature on the adaptation of brown adipose tissue to pregnancy in lean and obese rats
Authors: Budge Helen , Dellschaft Neele , Albustanji Layla , AlHarethi Enas , Perez G , Peter Aldiss , Symonds Michael
Published: June 2021

Introduction

Pregnancy has long been considered a physiological condition in which brown adipose tissue function is reduced. This was considered to represent a mechanism to enable energy conservation by the mother, although whether it is influenced by ambient temperature is unknown. It is now recognised that rodent studies examining brown fat function are conducted at a housing temperature well below thermoneutrality and as such are not immediately relevant to the human situation in which a majority of time is spent at thermoneutrality. The aim of our study was to examine the impact of an obesogenic diet on the mother prior to and during pregnancy and whether the housing temperature modulated the adaptations seen within interscapular brown fat through pregnancy.

Methods

Female rats were raised on a low fat (L) diet or a high fat, high sucrose diet (H) and housed at either a cool (20°C) or thermoneutral temperature (27°C) from 4 weeks of age, and 6 females of each group were tissue sampled at 10 weeks of age. The remaining females were mated and sampled at either 10d (mid‐gestation, n=6) or 19d gestation (late‐gestation, n=6). Gene expression and histological appearance of brown, interscapular adipose tissues was determined for brown (i.e. uncoupling protein (UCP)1) and white (i.e. leptin) characteristics as well as cell size.

Results

Gene expression for UCP1 was higher in unmated dams and at 19 but not 10 days of gestation in those animals maintained at 20°C, irrespective of diet. In these animals there was a marked decline in UCP1 at 10 days of gestation not seen in those kept at thermoneutrality. This was accompanied with a loss of UCP1 protein in obese, but not control dams. Gene expression for leptin was increased at thermoneutrality and rose through gestation in controls, but only increased in obese animals near to term. As expected the H diet raised white fat mass, but these animals had a similar body weight to controls, irrespective of rearing temperature. Brown fat mass was also higher with the H diet but only when maintained at 20°C, whereas mean cell size was increased at thermoneutrality.

Conclusions

The thermal environment has a major influence on the magnitude of loss of UCP1 through pregnancy. This adaptation does not occur when dams are maintained at thermoneutrality. Taken together these findings indicate that the impact of maternal obesity on the mother has been greatly under‐estimated in all studies to date which have been conducted at a standard (i.e. cool) thermal environment.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Importance of vasa nervorum in patients with chronic peripheral arterial disease
Authors: Settembre Nicla , Shaabi Hossam I. , Saba Charbel , Bouziane Zakariyae , Marc Labrousse , Sergueï Malikov
Published: June 2021

Introduction

The cutaneous perfusion of lower limbs influences the surgical treatment of different leg diseases.

In 1987, Taylor defined the concept of angiosome in his landmark anatomy study in the field of reconstructive plastic surgery. He divided the body into three‐dimensional anatomic units of tissue, “arteriosomes”, which is supplied by a specific source of arteries. In 2006, Attinger, in turn, divided the foot into six angiosomes supplied by the three main infra genicular arteries and their branches.

Our hypothesis is that skin vessels are different in patients with chronic limb ischemia and that the concept of angiosomes based on Attinger's study of healthy limbs is not applicable due to the development of collaterals.

Material and methods

The study was performed on 5 amputation limbs with severe chronic limb ischemia.

A barium sulfate suspension (Micropaque®) with colored liquid latex (25%: 75%) was injected under low pressure via femoral artery. Two days after the injection, a CT scan of the specimen was performed using a 64‐row MDCT (Lightspeed, General Electric Healthcare, Milwaukee, USA. As a second step, we dissected the arteries and marked the skin vessels guided by the CT images MPR and MIP.

Results

In our preliminary surgical anatomical study on 5 amputation specimens, we showed that the progressive evolution of atherosclerosis and the concomitant development of a supply network involving the vascularisation of the sensory nerves implement the limb and foot perfusion.

Conclusion

Arterial distribution in patients with chronic limb ischemia appears to follow partially the concept of angiosomes. Knowledge of collateral vascularization, especially vasa nervorum, can modify the strategies of surgical revascularization. In cases of total occlusion of the main arteries, the knowledge of the vasa nervorum network can be useful in patients in whom direct revascularisation on target angiosome following the angiosome theory is not applicable.

Support or Funding Information

No funding for this study

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Migration and differentiation of enteric neural crest cells in the embryonic gut explant cultured ex vivo
Authors: PAN TIANTIAN
Published: June 2021

Hirschsprung's disease (HSCR) is a common congenital gut motility disorder characterized by the reduction or absence of enteric neurons in the distal region of the colon. The Dominant megacolon (Dom) mutant mouse, which carries a spontaneous mutation in Sox10, exhibits HSCR‐like phenotypes, and hence has been used as an animal model of HSCR. It has been known that in Sox10Dom/+ mouse embryos, the migration and differentiation of neural crest cells (NCCs), which are progenitors of enteric neurons and glial cells, are abnormal, leading to hypoganglionosis or aganglionosis in the hindgut. In Sox10Dom/Dom homozygous embryos, the entire gut tube is aganglionic and the embryo dies before E13.5. However, it is still unknown whether hypoganglionic and aganglionic phenotypes exhibited by Dom mice is a result of abnormalities in NCCs only (cell‐autonomous effects), alterations of gut microenvironment through which NCCs migrate (niche effects), or both. Previously, an organotypic gut explant system has already been established, which allows ex vivo co‐culture of donor NCCs of different genotypes with a recipient embryonic gut segment isolated from embryos of the same or other genotypes. In the present study, E13.5 Dom mouse hindgut explants were used as recipient gut segments for transplantation of donor NCCs. Five days after cell transplantation, the hindgut explant cultured ex vivo appeared morphologically and histologically normal with rhythmic contractions and relaxations, indicating that the development of the hindgut explant ex vivo was similar to that in vivo. To obtain donor enteric neural crest cells (ENCCs), midgut segments which were genetically labeled with GFP were dissected from E11.5 mouse embryos and cultured on a fibronectin‐coated surface. ENCCs emigrated from the midgut segments were collected and transplanted to the hindgut explant, which was then cultured ex vivo for 5 days. We found that transplanted ENCCs survived, migrated, and differentiated into TuJ1‐immunoreative enteric neurons in normoganglionic and hypoganglionic segments of the hindgut explant. When transplanted to aganglionic segments of the hindgut, ENCCs were still able to differentiate into TuJ1‐immunoreactive neurons, but they were not able to migrate as far as those transplanted cells in the normoganglionic and hypoganglionic segments, and most of them stayed near the transplantation site without forming a normal neuronal network. Our results indicated that endogenous enteric neurons were required for the normal migration and integration of transplanted ENCCs within the hindgut explant.

Support or Funding Information

The work was supported by a grant from the Research Grants Council of the Hong Kong Special Administrative Region, China (Project No.: CUHK 14175017).

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.