bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hydrogen Sulfide Protects Against Sepsis‐Induced Myocardial Dysfunction by Inhibiting inflammation and Endoplasmic Reticulum Stress
Authors: Wu Yuming , Chen Yuhong , Jin Sheng , Teng Xu , Tian Danyang 
Published: June 2021

Hydrogen sulfide (H2S) is involved in the regulation of several physiologic processes and pathophysiologic conditions. However, the role of H2S in the development of Sepsis‐induced myocardial dysfunction (SIMD) remains unknown. In the present study, 10 patients with SIMD and 10 healthy controls were examined to investigate the role of H2S in SIMD. Compared with the Control group, the plasma levels of cardiac troponin I (cTnI), creatine kinase (CK), tumour necrosis factor‐α (TNF‐α) and interleukin‐1β (IL‐1β) were significantly higher in the SIMD group, but left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) were significantly lower. Furthermore, the plasma level of H2S was lower in the SIMD group, and the level of H2S was linearly correlated with the levels of LVEF and LVFS. Subsequently, we established a mouse model of SIMD induced by lipopolysaccharide (LPS) and used the H2S donor NaHS to clarify the role of H2S in the development of SIMD. LPS‐treated mice exhibited decreased levels of LVEF and LVFS and increased myocardial damage as well as increased levels of TNF‐α, IL‐1β, cTnI and CK. In addition, the protein levels of Toll‐like receptor (TLR)4 and endoplasmic reticulum stress (ERS) markers were over expressed in the SIMD mice; these changes were more severe in cystathionine γ‐lyase (CSE) knockout (CSE KO) mice. NaHS, which was administered intraperitoneally 3h after LPS treatment, could improve cardiac damage and strongly attenuated LPS‐induced inflammation and ERS in the SIMD mice. Overall, these findings indicate that H2S can protect against SIMD by inhibiting inflammation and ERS through the TLR4 signalling pathway.Support or Funding InformationThis study was supported by the National Natural Science Foundation of China (Grant 31671185, 31171098, 31871154).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Catestatin Improves Insulin Sensitivity by Promoting M1‐M2 Polarization and Inhibiting Obesity‐Induced Macrophage Infiltration and Gluconeogenesis in Liver
Authors: Mahata Sushil Kumar , Ying Wei , Muntjewerff Elke M , Mahata Sumana , Nicolasen Mara J.T. , Das Soumita , Bandyopadhyay Gautam Kumar , van den Bogaart Geert 
Published: June 2021

ObjectiveComponents of the innate and adaptive immune system are affected in obesity and Type 2 diabetes (T2D) and inflammation participates in the pathogenesis of T2D. The activation of the resident Kupffer cells and monocyte (Mc)‐derived recruited macrophages (McMΦs) in the liver contributes to obesity‐induced insulin resistance (IR) and T2D. Here, we sought to determine whether the Chromogranin A (CgA) peptide Catestatin (CST: human CgA352–372) regulates recruitment of macrophages and modulates metabolism in insulin‐resistant diet‐induced obese (DIO) mice as well as M1–M2 polarization in human monocytes.Methods and ResultsCST treatment of DIO mice diminished the expression of gluconeogenic genes, attenuated expression of pro‐inflammatory genes, increased expression of anti‐inflammatory genes in McMΦs, and inhibited infiltration of McMΦs, leading to improvement of insulin sensitivity. To gain better insights into the mechanism of action of CST, we isolated CD14+ subsets of monocytes from buffy coats from healthy individuals. The monocytes were cultured with M‐CSF towards undifferentiated MΦs and subsequently polarized towards pro‐inflammatory and anti‐inflammatory phenotypes with GM‐CSF, IFN‐γ and LPS or M‐CSF and IL4, respectively. RNA sequencing of proinflammatory MΦs revealed that CST decreased expression of proinflammatory genes in proinflammatory (e.g., IL23A, FCRLA, and IL1A) as well as in anti‐inflammatory MΦs (e.g., IL11RA, SP140, NLRCS, and TRIM34). In anti‐inflammatory macrophages, CST increased expression of anti‐inflammatory genes. Consistent with gene expression, CST exposure to anti‐inflammatory MΦs enhanced IL‐10 production but not in pro‐inflammatory MΦs, whereas CST inhibited TNFα and IL‐6 production in both cultures.ConclusionWe conclude that (i) CST attenuated macrophage mediated inflammation, resulting in improved insulin sensitivity in obese mice. (ii) CST promoted M1–M2 polarization by decreasing expression of proinflammatory cytokines and increasing expression of ant‐iinflammatory cytokines.Support or Funding InformationSupported by grants from the VA (I01BX000323 to S.K.M.), and the NWO Gravitation Programme 2013 (ICI‐024.002.009 to G.v.d.B.), and a Vidi grant from the Netherlands Organization for Scientific Research (NWO‐ALW VIDI 864.14.001 to G.v.d.BG.v.d.B.).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Activation of Formyl Peptide Receptor Precedes the Onset of Hypertension in Dahl Salt Sensitive Rats: Effects of Microbiota and Salt
Authors: Edwards Jonnelle , Galla Sarah , McCarthy Cameron G. , Bearss Nicole , Roy Shaunak , Joe Bina , Wenceslau Camilla F. 
Published: June 2021

AimsChronic activation of the immune system contributes to kidney injury and hypertension. Mitochondria carry hallmarks of their bacterial ancestry and thus have emerged as a significant source of inflammatogenic damage‐associated molecular patterns. One of these hallmarks is that they still use formylated peptides (NFPs) as an initiator of protein synthesis. NFPs activate formyl peptide receptor (FPR), a G‐protein coupled receptor, and leads to receptor internalization and desensitization. We have observed that mitochondrial NFPs are elevated in the circulation of spontaneously hypertensive rats (SHR) and FPR blockage decreases blood pressure in this strain. Also, we and others observed that FPR downregulates upon activation in immune and non‐immune cells. Given that cell death and gut dysbiosis are present in salt sensitive hypertension, we hypothesized that Dahl sensitive rats would have decreased FPR expression, and that the decrease could be attributed to increased plasma levels of circulating mitochondria and/or bacteria NFPs from the cell death and leaky gut, respectively, and contributes to hypertension. Sex differences were also investigated.MethodsMale and Female Dahl Sensitive (S) and Resistant (R) rats (6‐week old) were given a low (0.3% NaCl) or high salt diet (2% NaCl) for 38 days. Rats received normal drinking water or water supplemented with neomycin (0.5 g/l, GIBCO) for 3 weeks. Kidney samples were taken from all rats and used for mRNA extraction and purification. The mRNA was made into cDNA to test gene expression for FPR. Blood was collected to measure mitochondrial NFPs. T‐test *p<0.05; n= 8–11 for Dahl S and R; n=7 for Dahl + neomycin.Results and ConclusionFPR expression was downregulated 4‐fold from male and female Dahl S when compared to Dahl R (AU: FPR mRNA: Dahl R 4.5 ± 1.3 vs. Dahl S: 0.7 ± 0.2*) (Figure 1). This phenomenon was independent of salt and sex differences. Antibiotic treatment partially restored FPR expression from Dahl S animals when compared to Dahl S treated with neomycin (AU FPR mRNA: Dahl S 4.5 ± 1.3 vs. Dahl S‐neomycin treated: 2.74 ± 0.99*). ND6, a mitochondrial protein, is 1.7‐fold higher in plasma from Dahl S compared to Dahl R. Unexpected, salt diet did not change this parameter. We have observed for the first time that FPR is downregulated in Dahl animals independent of salt probably due to overstimulation of this receptor. Therefore, FPR activation due to increased levels of bacterial (NFPs) could be associated with the development of renal injury at an early age independently of salt and elevations in arterial pressure.Support or Funding InformationAmerican Heart Association (18POST34060003) and National Institutes of Health (K99GM118885 and R01HL143082)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Characterizing the Sensory and Affective Phenotype of Kappa Opioid Receptor Cre Knockin Mice in Response to Chronic Variable Stress and Inflammation
Authors: Zaheer Meeraal , Kolber Benedict J. 
Published: June 2021

Kappa Opioid Receptors (KORs) are an alternative opioid targeting site with the potential of targeting pain without the abuse associated with Mu Opioid Receptors (MORs). KORs have been linked to nociception and mood, and modulate responses to chemical, mechanical and thermal nociceptive stimuli. The KOR‐Cre knockin model is a novel method used to drive expression of the exogenous protein Cre recombinase using the endogenous KOR locus. While this model allows for study and visualization of KOR‐expressing cells, the full consequences of losing either one or both KOR alleles in these mice is not well characterized. We evaluated the sensory and affective phenotype of KOR‐Cre knockin homozygous and heterozygous mice before and after a 10‐day chronic variable stress (CVS) paradigm and the induction of inflammatory pain with Complete Freund's Adjuvant (CFA). We tested for mechanical (von Frey) and thermal (Hargreaves) sensory behavior, as well as depressive and anxiolytic affective behavior. We report sex‐specific differences in the sensory, but not affective phenotype in this model. We observe decreased depressive and increased anxiolytic behavior in KOR‐Cre heterozygous mice post‐CVS. Male mice exhibit mechanical hypersensitivity while both sexes of KOR‐Cre homozygous mice exhibit thermal hyposensitivity post‐CVS. Administration of CFA elicits contralateral thermal hyposensitivity in male KOR‐Cre heterozygous and female homozygous mice, while no changes in mechanical sensitivity are observed in either sex. We conclude that sex‐specific differences must be accounted for when conducting pain research, as CVS and CFA results in variation in pain incidence between sexes. Moreover, lack of activity in KOR‐Cre homozygous mice post‐CVS may result in signs of pain resilience in the absence of the receptor under stress. Furthermore, hyposensitivity post‐CFA could indicate that pain‐related function in KORs may act through a synergistic compensatory mechanism combining the activity of both MORs and KORs. Our results suggest that caution should be used when substituting KOR‐Cre heterozygous mice for WT mice. By characterizing this model, we provide a baseline for which the model can be compared to when conducting research on KOR‐positive cells.Support or Funding InformationResearch supported by NIH R25NS100118 (BJK, KJT, MC, MRM) and the APS UGRSF (MZ).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Statin Therapy Enhances Reflex Cutaneous Vasodilation in Formerly Hypercholesterolemic Older Adults by Improving Neurovascular Coupling
Authors: Greaney Jody L , Stanhewicz Anna E , Kenney W. Larry 
Published: June 2021

Reflex cutaneous vasodilation is attenuated in healthy human aging and is mediated by alterations in both central (sympathetic outflow) and peripheral (microvascular endothelial) function. Hypercholesterolemia, a primary risk factor for cardiovascular disease, is associated with increased sympathetic nervous system activity and further impairments in endothelial function. Independent of their lipid‐lowering effect, HMG‐CoA reductase inhibitors (statins) – the most commonly prescribed medication in the U.S. – reduce sympathetic outflow and augment endothelium‐dependent dilation. However, whether statin therapy improves the relation between skin sympathetic nervous system activity (SSNA) and cutaneous vascular conductance (CVC) during passive heat stress is unknown. We hypothesized that (1) hypercholesterolemic older adults would demonstrate blunted increases in both SSNA and CVC during passive heating and (2) chronic statin treatment would improve the response range and sensitivity of the SSNA:CVC relation. Reflex vasodilation was induced in 13 healthy normocholesterolemic older adults [62±2 yrs; low‐density lipoprotein (LDL) 113±7 mg/dl), 10 hypercholesterolemic older adults (60±1 yrs; LDL 183±2 mg/dl), and 10 previously hypercholesterolemic older adults now treated with a lipophilic statin (10–40 mg daily) to normalize LDL (64±1 yrs; LDL 102±2 mg/dl) using a water‐perfused suit to elevate oral temperature (Tor) by 1.0°C. SSNA (peroneal microneurography) and red cell flux (laser Doppler flowmetry) in the innervated dermatome (the dorsum of foot) were continuously measured. SSNA was normalized to, and expressed as, a percentage of baseline and CVC was calculated as flux/mean arterial pressure and expressed as a percentage of maximal CVC (local heating to 43°C). Mean arterial pressure, baseline CVC, and maximal CVC were not significantly different among groups (all p>0.05). During passive heating, the increase in SSNA was not different among groups (normal: Δ=393±96%, high: Δ=311±120%, and statin: Δ=256±90%; p=0.11). Reflex vasodilation was blunted in hypercholesterolemic adults, but not in statin‐treated adults, compared to normocholesterolemic adults (normal: 36±1%CVCmax, high: 32±1%CVCmax, and statin: 38±1%CVCmax respectively, at ΔTor=1.0°C; p<0.01). There were no differences among groups for the slope of the ΔSSNA:ΔCVC relation (normal: 0.06±0.00, high: 0.07±0.01, and statin: 0.07±0.01, p=0.91); however, this relation was shifted upward in statin‐treated adults (y‐intercept; normal: 3.1±0.9, high: 4.0±0.9, and statin: 7.3±1.3; p=0.001). These data demonstrate that chronic statin treatment improves reflex cutaneous vasodilation in formerly hypercholesterolemic older adults, in part via increases in end‐organ responsiveness to sympathetic outflow during passive heat stress.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Probiotic supplementation improves total and exogenous CHO oxidation in trained male cyclists: A randomized, double‐blind, placebo‐controlled cross‐over trial
Authors: Pugh Jamie , Wagenmakers Anton , Morton James , Doran Dominic , Fielding Barbara , Fleming Simon , Close Graeme 
Published: June 2021

BackgroundIn vitro and animal studies suggest probiotic supplementation can enhance intestinal absorption and whole body oxidation rates of glucose.ObjectiveThis study investigated the effects of multi‐strain probiotics supplementation on substrate utilization, markers of gastrointestinal permeability and damage and subjective symptoms of discomfort and performance during endurance cycling.Methods and DesignNine male cyclists (age 23 ± 4 yrs, V̇O2max 62.1 ± 4.7 mL·kg−1·min−1) were randomized to two periods of daily supplementation with a probiotics capsule (25 billion CFU of Lactobacillus acidophilus (CUL60 and CUL21), Bifidobacterium bifidum (CUL20), Bifidobacterium animalis subsp. lactis (CUL34), Proven Probiotics) or placebo for four weeks, separated by a 14‐day washout period (double‐blind cross‐over trial). After each supplementation period, cyclists consumed a 10% maltodextrin solution (initial 8 mL·kg−1 bolus at commencement of exercise and 2 mL·kg−1 every subsequent 15 min) while exercising for 120 minutes at 55% Wmax. This was followed immediately by a 100 kJ time trial performance test. Markers of GI permeability, damage and GI discomfort were assessed. Oxidation rates of the ingested maltodextrin drinks were calculated from the 13C‐enrichment of plasma glucose and breath 13CO2 production during the 120 minutes exercise period.ResultsProbiotic supplementation resulted in an increase of total carbohydrate (CHO) oxidation (2.12 ± 0.30 vs 1.81 ± 0.44 g·min1, P = 0.019) and the peak oxidation of an ingested maltodextrin drink (0.84 ± 0.10 vs 0.77 ± 0.09 g·min−1 of glucose equivalents, P = 0.016) during exercise. Total fat oxidation was reduced following probiotic supplementation compared to placebo (P = 0.004). There were also significant differences in plasma insulin, NEFA and glycerol between trials. Differences between markers of GI damage and permeability were not significant, as was time trial performance (P > 0.05).ConclusionsProbiotic supplementation enhances total and ingested CHO oxidation while simultaneously attenuating total fat oxidation during moderate intensity cycling. Probiotic supplementation did not change GI symptoms, time trial performance and markers of intestinal damage and permeability.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The Value of Cadaveric Dissection in Undergraduate Medical Education: A Student's Perspective on the State of Affairs
Authors: Smith Jake 
Published: June 2021

Throughout the past 15 years, medical schools around the world have interrogated the value of cadaveric dissection in anatomy courses during undergraduate medical education (UME) in light of advances in medical imaging, increasing costs of UME, decreased time allotted to anatomy education, and the availability of high‐quality prosections and models.Proponents of dissection argue that in addition to gaining knowledge of anatomy at the basic science level, medical students develop qualities vital to the practice of medicine such as developing clinician habits‐of‐mind, understanding 3D anatomy as it relates to medical imaging, and reflecting on death and dying. Furthermore, medical students themselves feel as though dissection enhances their ability to work as a team, undergo professional development, and come to terms with death. Proponents also note that deep learning of any subject is cultivated by direct experiential learning, which may describe dissection to a greater degree than other learning modalities.Detractors, however, argue that such qualities can be instilled in students at other times throughout UME, and that because physicians primarily interact with anatomy through medical imaging and living models, the time spent dissecting may be better spent gaining proficiency with these modalities. Other detractors have claimed that many of the benefits of dissection such as touch‐mediated learning and exposure to death and dying can be obtained through prosection. Detractors also note that dissection has been shown to be no better than other modalities in impacting student performance on anatomy exams.This presentation will review the existing literature regarding the dissection vs prosection debate and provide perceptional feedback on both instructional methodologies from the perspective of a current medical student who has experience teaching and learning anatomy through various modalities at the undergraduate, graduate, and professional school levels.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Gender specific effects on growth, postural muscles and deep pressure sensitivity in hindlimb unloading
Authors: Chowdhury Parimal , Pathak Rupak , Griffin Robert J , Mehta Rahul , Dobretsov Maxim 
Published: June 2021

Hind limb unloading is a NASA validated animal model of simulated weightlessness. The aim of this study is to test the gender‐specific effects in a hindlimb suspended rat model of microgravity.MethodsAdult male and female rats were suspended for two weeks using two different methods. A separate group of male and female rats served as control (non‐suspended). Body weights, food and water consumption, soleus muscle weights, pressure‐pain thresholds (PPT) and insulin levels were measured.ResultsFor a given gender, none of measured characteristics differed between the two suspended rats. Therefore the results with different suspension techniques were combined and pooled together for further analysis. Data show that food and water intakes were not different between genders and between control and suspended groups. Compared to control males, control female rats had the same PPT value, but weighed less, had lower soleus muscle mass and gained weight slower. HLS nearly canceled the weight gain and resulted in the development of pressure hyperalgesia in both gender groups. However, HLS‐associated soleus muscle atrophy was detected in male rats only. Furthermore, in a sub‐group of experiments in which both PPT and plasma insulin were measured, HLS was found to decrease insulin concentrations and affect pain thresholds in male rats only.ConclusionsOverall HLS appear to influence growth, postural muscles and deep pressure sensitivity of males and it is stronger and consistent than those of female ratsSupport or Funding InformationSupported by a grant from Arkansas Space Grant ConsortiumThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Histamine receptor antagonists have the capacity to alter in vivo human sweating: implications for hypohidrosis
Authors: Wilson Thad E. , Meade Stephanie , Stump Corey , Skaggs Kendra , Banwait Sumeet , Galloway Samantha , Garrett Jason 
Published: June 2021

An atopic dermatitis mouse model has identified histamine and the histamine type‐1 receptor (H1R) pathway to be a mechanism of disease‐induced hypohidrosis. To begin to translate these findings into in vivo human skin, we tested the hypothesis that intradermal perfused H1R antagonist pyrilamine maleate would accentuate local eccrine sweating induced sympathetically via whole‐body heat stress. Two intradermal microdialysis probes were placed into the dorsal forearm of 3 healthy female and 2 healthy male subjects (health determined by health history and physical exam; age = 25±1 yrs; and BMI = 25.3±3.5 kg/m2) to perfuse (5 μL/min) of pyrilamine maleate (3 mM) or the vehicle (lactated Ringer's) while measuring sweat rate (capacitance hygrometry) directly over the microdialysis membrane. Whole body heating (46°C water perfusion of a high‐density tube‐lined suit) increased intestinal temperature (pill telemetry) by 1.0°C from 36.9±0.2°C, heart rate (ECG) by 32±5 bpm, calf blood flow (venous occlusion plethysmography) by 7.8±1.4 ml/100 ml tissue, and whole‐body sweat loss of 1.5±0.2 kg but did not significantly alter mean arterial pressure. Mean skin temperature was clamped under the suit at 38–39°C, while uncovered forearm skin temperature increased from 29.6±0.3 to 35.1±0.6°C. Pyrilamine maleate increased local sweat rate compared to the vehicle control beginning at 35 min of whole‐body heating (intestinal temperature of 37.1±0.2°C) and this difference remained throughout the heat stress (group: P=0.008, time: P<0.001, and interaction: P<0.001). These data indicate that the H1R mechanism has the capacity to alter sweat rate during a physiological induced sudorific perturbation known to affect histamine concentration in human skin. Thus, it is possible that this mechanism of hypohydrosis could be a viable target in individuals with atopic dermatitis.Support or Funding InformationLaboratory support: NIH AR069912This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.