bluuebunny/crossref_metadata_2025_split huggingface dataset:
Muscle mitochondrial dysfunction at different stages of chronic kidney disease (CKD)
Authors: Gamboa Jorge , Keller Chad A. , Falck Aaron M. , Roshanravan Baback , Brown Nancy J. , Ikizler Talat Alp 
Published: June 2021

Sarcopenia and frailty are commonly observed in patients with CKD. Mitochondria, as the principal source of energy, are important for proper muscle function, and may play a role in frailty and sarcopenia. We have previously reported reduced mitochondrial content in patients with CKD on maintenance hemodialysis (MHD) probably due to increased mitophagy. We have also found smaller mitochondria in skeletal muscle of patients on MHD, which may be the consequence of increased mitochondrial fission. We now evaluated the hypothesis that mitochondrial dysfunction is associated with the severity of chronic kidney disease (CKD). For this purpose we evaluated 22 patients on MHD, 20 patients with history of CKD stage 3–5 but not on MHD, and 21 controls with no history of CKD that were matched by gender, history of diabetes, BMI, and race. We measured in vivo mitochondrial function by 31‐phosphorus magnetic resonance spectroscopy (31P‐MRS) in the quadriceps muscle. We used the half time recovery of phosphocreatine (P‐Cr) after a brief exercise as the measure of mitochondrial function. A faster recovery correlates with better mitochondrial function. We also measured physical activity using the six‐minute walk test. Controls and patients on MHD were similar in terms of age (46.9±9.5 vs. 47.7±11.7) but younger compared to patients with CKD stage 3–5 (63.6±9.0). BMI was similar among the groups (30.1±5.9, 30.4±5.2, and 29.6±7.9; controls CKD stage 3–5, and patients on MHD, respectively). We found that the half time recovery of P‐Cr was faster in controls compared to patients on MHD, but similar to patients with CKD stage 3–5 (Figure 1A). We also found that physical activity measured by 6 minute walk test was higher in controls compared to patients with CKD stage 3–5 and patients on MHD (Figure 1B). There was significant negative correlation between physical activity and mitochondrial function (R2=0.37, p<0.001). Our data suggest that in vivo mitochondrial function is impaired in patients on MHD but not in patients with CKD stage 3–5 despite a progressive decrease in physical activity among the groups. Further studies are required to evaluate the efficacy of interventions, such as mitochondrial targeted‐therapies or exercise, on mitochondrial function in patients with CKD.Support or Funding InformationNIH/NIDDK (K23DK100533)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Indispensably evil! The role of oxygen in nitric‐oxide dependent endothelial function
Authors: Pedrinolla Anna , Savoldelli Aldo , Scafidas Spyros , Giuriato Gaia , Fornasiero Alessandro , Pellegrini Barbara , Bortolan Lorenzo , Schena Federico , Venturelli Massimo 
Published: June 2021

BackgroundEndothelium derived nitric oxide (NO) is crucial in preserving vascular tone. Several evidence shows that NO bioavailability and utilization is regulated by oxygen (O2) concentration. However, there are still not sufficient experimental data to show how O2 concentration affects NO‐dependent endothelial function in vasculature.AimTo investigate the role of O2 concentration on NO‐dependent endothelial function in vasculature. We hypothesized that different O2 concentration would have elicited different responses during single passive limb movement (sPLM) test, which is known to be an index of NO‐dependent systemic endothelial function.MethodsEndothelium‐dependent dilation was measured in 7 active men (age, 34±12 years; weight, 70±8 kg, height, 173±4 cm, VO2max 55.9±10.5 ml/min/kg) by means of sPLM test performed in a normobaric‐hypoxic chamber in two conditions: Normoxic (N; FiO2 ~20.9%), and Hypoxic (H; FiO2 ~16.25%). For the two conditions femoral artery diameter, as well as basal blood flow (BF), Peak BF, ΔPeak BF, area under the curve (AUC) were calculated.ResultsIn H, femoral artery diameter did not change (−2.2±3.7%, p=0.675), basal BF significantly increased (+24±9%, p=0.043), as well as peak BF (+32±10%, p=0.034), ΔPeak BF (+34±15%, p=0.040), and AUC (+44±16%, p=0.018).ConclusionAs hypotized, different O2 concentrations provoked different responses during the sPLM test. These results suggest an O2‐dependent NO availability and utilization, which may play an essential role in endothelial function during hypoxia.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 Role of Interleukin‐2 (IL‐2) in Natural Killer Cell (NK) Activation and Hypertension in a Preclinical Rat Model of Preeclampsia
Authors: Cunningham Mark W. , Ibrahim Tarek , Cornelius Denise , Amaral Lorena , Vaka Venkata Ramana , LaMarca Babbette 
Published: June 2021

Women with preeclampsia (PE) have hypertension, placental ischemia, increased pro‐inflammatory cells (natural killer (NK) and Th1 cells) and cytokines, and intrauterine growth restriction (IUGR). Interleukin‐2 (IL‐2) is a Th1 cytokine that stimulates NK cell activation. We hypothesize that IL‐2 is one mechanism whereby Th1 cells, which are activated in response to placental ischemia, mediate NK cell activation, hypertension, and IUGR during pregnancy. The objective of this study was 2 fold: 1.) to determine if elevated IL‐2 during pregnancy will increase blood pressure, NK cell activation, and cause IUGR. 2.) to determine if blockade of IL‐2 (basiliximab) will decrease blood pressure, NK cell activation, and improve pup weight in the reduce uterine perfusion pressure (RUPP) preclinical rat model of PE The RUPP rat is a model of placental ischemia during pregnancy which has increased IL‐2 levels and mimics many of the symptoms of PE.MethodsOn gestational day 14, normal pregnant (NP) rats received IL‐2 infusion (0.20 ng/ml) via mini‐osmotic pump; while RUPP rats receive basiliximab (0.07 mg/per rat) via IV infusion. On day 19, conscious blood pressure (MAP), pups, placentas, and blood were collected. Flow cytometry was used for quantification of NK cells.ResultsIL‐2 infusion did not increase MAP (106 ± 3 vs. 100 ± 2 mmHg) nor change pup weight (2.24 ± 0.06 vs. 2.33 ± 0.06 g). However, IL‐2 infusion decreased placental weight (0.60 ± 0.02 vs. 0.67 ± 0.02 g, p<0.05 vs. NP) and increased circulating activated NK cells (10.4 ± 1.8 vs. 3.1 ± 1%, p<0.05 vs. NP). RUPPs rats exhibit elevated MAP (123 ± 3 vs. 103 ± 3 mmHg, p<0.05 vs. NP), placental (14.1 ± 2.9 vs. 7.8 ± 0.6%, p<0.05 vs. NP), and circulating (16.6 ± 1.3 vs. 7.7 ± 0.9%, p<0.05 vs. NP) activated NK cells. Basiliximab treatment had no effect to lower MAP (123 ± 2 vs. 123 ± 3 mmHg) or improve pup weight (2.08 ± 0.07 vs. 2.04 ± 0.07 g) and placental weight (0.59 ± 0.03 vs. 0.53 ±0.04 g) in RUPP rats. However, basiliximab decreased total placental NK cells in RUPP rats (4.6 ± 1.4 vs. 14.1 ± 2.9%, p<0.05 RUPP + basiliximab vs. RUPP).ConclusionIL‐2 appears to play a major role in NK cell activation during PE that could possibly impact placental health without causing increases in blood pressure during pregnancy.Support or Funding InformationResearch Supported by T32HL105324 and HL130456This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Association of Chronic Nicotine Inhalation with Hypertension in Mice
Authors: Fuchs Robert Marcus , Oakes Joshua , Basting Tyler , Lobell Thomas , Gilpin Nicholas , Gardner Jason , Yue Xinping , Lazartigues Eric 
Published: June 2021

For decades it has been known that chronic tobacco smoke exposure is a risk factor for hypertension, predisposing to cardiovascular pathologies including stroke and heart failure. However, no prior study has evaluated the role of inhaled nicotine per se. Previous investigations found that subcutaneously‐administered nicotine acutely increases expression of angiotensin‐converting enzyme (ACE) and the angiotensin receptor (AT1R). These findings suggest RAS dysfunction may mediate nicotine‐induced hypertension through either increased expression of pro‐hypertensive proteins (ACE/AT1R) or suppressed expression of compensatory agents (ACE2/MasR).Accordingly, we hypothesized that chronic nicotine inhalation promotes hypertension by inducing RAS dysfunction within autonomic brain nuclei. To test this hypothesis we exposed male (n = 64) and female (n = 44) mice to air (control) or twelve hours of nicotine vapor nightly for eight weeks. Mean nocturnal systolic blood pressure (telemetry) increased between the baseline and final week of nicotine exposure (males: +19.71 ±0.65 mmHg, F = 528.2, n = 5, p < 0.0001; females: +14.04 ±0.85 mmHg, F = 322.7, n = 4, p < 0.0001). In females, a trend towards elevated urinary norepinephrine was observed (t = 1.751, p = 0.0993). In a pilot study, when we exposed rats for 3 weeks to 14 hours of nicotine nightly, the hypothalamic ACE2 mRNA levels were reduced (t = 2.490, p < 0.05). In mice we found a trend towards increased expression of MasR mRNA in this brain region (t = 2.373, p = 0.0766).Together, these findings suggest that nicotine inhalation contributes to high blood pressure, possibly through enhanced sympathetic activity. Mechanistically, our pilot data indicate that impaired ACE2 expression occurs in tandem with a compensatory increase in MasR in the hypothalamus of subjects inhaling nicotine. Future studies will elucidate activity of additional RAS contributors in cell culture and clarify the nature of autonomic dysfunction in vivo (e.g., increased sympathetic output vs decreased vagal tone). Collectively, this project will provide crucial information regarding the risk of hypertension in users of nicotine inhalation devices (i.e. e‐cigarettes), improving the ability of clinicians to treat this condition.Support or Funding InformationThis work was supported by NIH NHLBI grants 1R01 HL135635 and 2R01 HL093178.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Sex Differences And Stress Alter The Vagally‐Mediated Gastric Response To Oxytocin In Rats
Authors: Zimmerman Julia E. , Jiang Yanyan , Travagli R. Alberto 
Published: June 2021

Stress and stress maladaptation play critical roles in the development of functional gastrointestinal (GI) disorders. Females have a higher incidence of functional GI disorders, likely due to fluctuations in estrogen levels, which we have shown to correlate with increased inhibitory vagal output to the GI tract. Previous studies have shown that levels of anti‐stress hormone oxytocin vary in response to stress: the more oxytocin the better the individual copes with stressful events. Furthermore, our previous studies (PMC4287746) showed that acute stress induces plastic changes in the vagally‐mediated gastric response to oxytocin, however gastric motility responses to brainstem application of oxytocin in male vs female in response to chronic stress are not yet known.The aim of this study was to test the hypothesis that sex differences and stress alter the gastric, vagally‐mediated response to oxytocin.SD rats were divided into the following groups 1) male, 2) low estrogen female, and 3) high estrogen female. Rats were further subdivided into the following groups: i) control, and 5 consecutive days of ii) chronic repetitive homotypic stress (these rats adapt to stress; CHo), and iii) chronic repetitive heterotypic stress (these rats do not adapt to stress; CHe). At the end of the stress load, rats were anaesthetized and strain gauges were sewn to the anterior stomach to record antrum and corpus tone and motility variation upon oxytocin microinjected in the dorsal motor nucleus of the vagus to record the changes in corpus and antrum. The postganglionic vagal pathway affected by oxytocin was investigated via i.v. injection of L‐NAME, VIP antagonist or bethanechol.Focusing on antrum motility, but similar data were obtained with corpus tone and motility as well as antrum tone, our results suggest: i) in male rats (N=4 for all) the oxytocin induced inhibition in antral motility was attenuated significantly by L‐NAME only in controls (from 65±5% to 23±7% decrease from baseline), while in stressed animals, the response was mediated also via engagement of a VIP‐dependent pathway. ii) in all the groups from low or high estrogen females (N=3 for all), the oxytocin‐mediated gastric response was regulated via both L‐NAME (from 53±5% to 43±7% decrease from baseline, in high estrogen control) and VIP‐sensitive pathways (from 53±5 to 8±36% decrease from baseline, in high estrogen control).In conclusion, our data indicate that females appear to respond to oxytocin to a lesser extent than males, and the vagally‐mediated pathways controlling tone and motility by females are similar to those used by stressed males. These observations may lead to a better explanation of the higher incidence of functional GI disorders in females.Support or Funding InformationAmerican Physiological Society, Undergraduate Summer Research FellowshipThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Probiotic Administration in an Endometriosis Animal Model Can Influence the Gut Microbiota and Gut‐Brain Axis to Counteract the Effects of Stress
Authors: Chompre Gladys , Cruz Myrella L. , Arroyo Gerardo A. , Rivera Raquel M. , Colon Maria C. , Appleyard Caroline B. 
Published: June 2021

Endometriosis is characterized by endometrial tissue growing in areas outside the reproductive system resulting in discomfort, pain, and infertility. Environmental factors such as stress have been suggested to exacerbate the condition, and our group has previously shown that stress can increase lesion size in a rat model. Animal studies have found increased gram‐negative bacteria in the gut microbiome of endometriosis animals and that oral administration of Lactobacillus gasseri can decrease lesion size however it is unclear whether probiotic use could counteract the effects of stress in our model.HypothesisAdministration of a probiotic mixture can decrease endometrial implants in animals under stress via modulation of the intestinal microflora.MethodsEndometriosis was induced in female Sprague Dawley Rats (11–12/group) by implanting uterine tissue next to the intestinal mesentery on day 0. Animals were allowed to recover for seven days before administering placebo (Pl) or probiotic (Pro) in drinking water until time of sacrifice (day 60). Stressed (S) animals were subjected to water avoidance for 60 mins/day (days 14–20). Non stressed (NS) animals stayed in a clean cage. Anxiety was measured before and after stress using open field. Fecal bacterial composition was analyzed at four time points: before surgery, before stress, after stress, and at sacrifice.ResultsESPl group had increased anxiety and development of more endometrial lesions (91.27%) which were of a larger size (38.31 ± 6.90mm2) compared with ENSPl (62.50%; 17.94 ± 3.90mm2, p<0.05). Administration of the probiotic (ESPro) decreased the number developed (56.25%), the size of the lesions (14.33 ± 3.17mm2, p<0.01), as well as colonic damage (p<0.05). Stress caused changes in the microflora including lower alpha diversity and altered firmicutes/bacteroidetes ratio, and these changes appeared to be reversed in those animals receiving the probiotic. Probiotic administration also modulated the effect of stress on bacterial abundance at the genus level.ConclusionsOur results suggest that the gut microflora plays an important role in the stress induced‐exacerbation of the endometriosis symptoms in this animal model since administration of a probiotic mixture can decrease lesion size. This offers the potential for further exploration of this complementary therapy in the patient population.Support or Funding InformationSupported in part by P20 GM103475‐15, R25GM082406, 2R25GM096955 & MD007579.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Fasting‐Mimicking Diet and Risk Factors for Aging, Diabetes, Cancer and Cardiovascular Disease
Authors: Shelechi Mahshid , Wei Min , Brandhorst Sebastian , Morgan Todd , Dorff Tanya , Hong kurt 
Published: June 2021

BackgroundProlonged fasting in which only water is consumed for 2 days or more has been shown to reduce pro‐growth signaling, activate cellular protection mechanisms and promote protection against cancer, diabetes, heart disease and neurodegenerative diseases. Since prolonged fasting is difficult for most human subjects, we developed a Fasting Mimicking Diet (FMD) which is a low calorie, low protein, plant‐based meal plan for 5 continuous days. During periods of low calorie intake, the body enters a protected mode, removes damaged cells and tissues, and undergoes self‐repair.Methods100 participants without a diagnosed medical condition in the preceding six months were enrolled based on Inclusion criteria (generally healthy adult volunteers, 18–70 years of age, body mass index: 18.5 and up). This study is designed as a randomized cross‐over trial, includes two arms: Control and multi‐cycle special 5‐day dietary regimen (Diet, 3 cycles). We evaluated the effects of the FMD on risk factors and markers for aging, cancer, metabolic syndrome and cardiovascular diseases.ResultsFor all subjects who completed 3 FMD cycles (combining both FMD arms), body weight, BMI, total body fat, trunk fat, absolute lean body mass, waist circumference, IGF‐1, systolic and diastolic blood pressure, total cholesterol and LDL were significantly reduced (P<0.05) and relative lean body mass (p=0.0002) was increased.ConclusionsFMD cycles are effective in improving an array of metabolic markers/risk factors associated with poor health and aging and in contributing to the treatment and prevention of multiple age‐related diseases.Support or Funding InformationFunding was provided by the USC Edna Jones chair fund. Dr. Mack's contributions were provided through the Southern California Clinical and Translational Science Institute (SCCTSI) supported by NIH ULTR001855
A Mathematical Model for the Population Dynamics of Intestinal Microbiota: Obese Versus Healthy Gastrointestinal Tract
Authors: Arango Felipe Giron , Umaña Alejandro Pizano , Prieto Paola Calvachi , Cordovez Juan Manuel 
Published: June 2021

IntroductionThe term microbiota refers to a community of microorganisms that are located in a certain space that have a symbiotic relationship with the host cells, in this specific case the human gastrointestinal tract. This interaction provides support to the tract in different functional aspects such as trophic functions, protection (immune system) and metabolism. There has been evidenced that intestinal microbiota plays an important role in synthesis, metabolism, and other functions associated to the nutrients and micronutrients that can lead to healthy or obese patients. In this work we aimed to understand and model the population dynamics of the intestinal microbiota.MethodsA mathematical model was design based on the gastrointestinal tract seen as a single tubular structure composed of Esophagus, Stomach, Small intestine (Duodenum, Jejunum and ileum) and colon. Only one major phylum of microorganisms (Either Firmicutes or Bacteroidetes) was included according to anatomical and physiological characteristics and in terms of its relative abundance in each part of the tract. The model included the subject's diet and activity level as inputs. Parameters for the model were obtained from a literature review. The model was implemented in Matlab and produced microorganism distribution (i.e. spatial concentration). We model different diets and pathological conditions.ResultsThe model reveals an expected growth of either Firmicutes or Bacteriodetes associated with the amount of nutrient and carrying capacity of the gastrointestinal tract. These results are in agreement with several reports obtained from the literature. In addition, the model showed an interesting stabilization of bacterial population under some circumstances depending on the segment of the gastro intestinal tract. Bacterial population is sensitive to diet and exercise.ConclusionsThe model can be used to predict the population dynamics under different diets and furthermore could be implemented as an important tool for bariatric surgery patients. The model can also shed some light on how to prevent the progression from overweight to obese just by changing the diet understanding the dynamics of gastrointestinal tract population.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Computational Analysis of 1,2‐dialkynylpyrroles
Authors: Bondoc Joshua , Kerwin Sean 
Published: June 2021

Computational chemistry can be used to quickly predict the properties of molecules. We are interested in studying the potential of 1,2‐dialkynylpyrroles to undergo a thermal Bergan cyclization‐triggered rearrangement to reactive diradical intermediates that display cytotoxic activity. These diradical intermediates have garnered much interest in the scientific community as a potential tumor suppressing compound. In order to analyze these diradicals, a B3LYP hybrid functional with a 6–31G** basis set was used to predict the electronic energy of each intermediate and transition state in the reaction. The electronic energy values for each step in the reaction were used to construct an energy diagram that quantified the energy gap between the intermediates and transition states. The goal of this experiment was to create an analogue of a dialkynylpyrrole that maximized the energy gap between the diradical singlet and the Retro Bergman transition state, and minimized the energy gap between the diradical singlet and the diradical triplet. An analogue that produced a diradical with these properties would be long lived and reactive.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.