bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pseudocannabinoid H4CBD Reduces Cardiac Damage Indicator 4HNE in OLETF (Otsuka Long Evans Tokushima Fatty) Rats
Authors: Hernandez Garcia Marisol , Wilson Jessica N. , Mendez Dora A. , Ortiz Rudy , Mascal Mark 
Published: May 2024

Cardiovascular disease (CVD) is a leading cause of death globally and MetS is an associated precursor of CVD. Of the 6 known cluster factor conditions of MetS, obesity, and poor glucose tolerance are known to contribute to high lipid peroxidation, which can contribute to the generation of damaging free radical species and a pro-oxidant system. Cannabidiol (CBD) is a known antioxidant and a growing understanding of CBD analogs and pseudocannabinoids, like H4CBD, implicate similar antioxidant effects. However, little is known about the effects of CBD analogs on MetS-associated cardiac tissue damage. To better understand these effects during extreme metabolic dysfunction, 41-weeks-old animals were assigned into three groups, (n=8/group): (1) one-lean-strain control, Long Evans Tokushima Otsuka (LETO), (2) untreated OLETF, and (3) OLETF + H4CBD (200 mg/kg/day x 4 weeks). Our hypothesis focuses on the prospect that ongoing treatment with H4CBD in a MetS model using Otsuka Long-Evans Tokushima Fatty (OLETF) rats will reduce indicators of lipid peroxidation including 4-hydroxynonenal (4HNE), a toxic end product of lipid peroxidation. After the 4-week treatment, cardiac tissue was analyzed for 4-hydroxynonenal (4HNE) protein expression. We found that H4CBD decreased cardiac 4HNE protein expression in treated OLETF rats by 68% (p<0.05) compared to OLETF control, which indicates H4CBD attenuated cardiac lipid peroxidation overall. Although the 4-week treatment of H4CBD was not suffcient to ameliorate MetS-associated hypertension, the reduction of 4HNE suggests that the attenuation of cardiac damage is independent of arterial pressure. These data indicate that H4CBD and its derivatives hold promise for therapeutic use in managing CVD and related metabolic syndrome-associated pathologies. Undergraduate Research Training Initiative for Student Enhancement (U-RISE), Center for Medical Cannabis Research. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Addressing Disparities Between Physician Rated and Self-Reported Dyspnea Using Machine Learning
Authors: Mkrtchyan Karapet , Lohn Borena , Qazi Anser , Ma Shujie , Heinrich Erica 
Published: May 2024

Nearly 50% of intensive care and 25% of tertiary care patients experience dyspnea, or the sensation of unsatisfied breathing. Dyspnea decreases quality of life, impacts clinical outcomes, and can have long standing psychological consequences for some patients. Current methods of identifying dyspnea severity (such as the respiratory distress observation scale or RDOS) lack suffcient quantifiable measurements of dyspnea to accurately predict its severity. In our testing, while the RDOS does have predictive power, it frequently produces underestimates compared to self-reported dyspnea severity (r = 0.32; p = 0.0081). Furthermore, dyspnea severity can change throughout the day, requiring healthcare professionals to conduct RDOS evaluations multiple times to attempt to meet patient needs. Therefore, there is an urgent need for continuous, accurate monitoring of dyspnea severity in the hospital setting. To address this need, we are using non-invasive data collected during induced bouts of dyspnea to train a machine learning (ML) algorithm in dyspnea prediction. We employ a steady-state end-tidal forcing breathing system and adjust end-tidal gas tensions manually while collecting PO­­­­2, PCO2, SpO2, and ventilation data. Preliminary findings show several physiological and demographic factors independently correlate to dyspnea severity, including BMI (r = 0.49; p = 0.007), end-tidal PCO­­2 (r = 0.33; p = 0.008), and inspired PO2 (r = -0.25; p = 0.043). We achieved an accuracy of 84%, 83.3%, and 82% in-dataset predictions using k-nearest neighbor, random forest, and logistic regression approaches respectively. Several physiological biomarkers and demographic factors were used as inputs and self-reported dyspnea was used as the predicted output. These findings show promise for the use of ML in dyspnea prediction. With further testing and use of a broader participant population, it may be possible to use ML models such as these to improve patient outcomes and overall quality of life. University of California, Riverside. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
A Hypovolemic Infusion of Human Methemoglobin in Golden Syrian Hamsters Provides Insight on its effect on the Microcirculation
Authors: Munoz Carlos , Lucas Daniela , Martinez Jacinda , R. Muller Cynthia , Govender Krianthan , Palmer Andre F. , Cabrales Pedro 
Published: May 2024

Introduction: Hemoglobin (HbFe(II)) plays a crucial role in transporting oxygen to tissues for metabolic needs. However, this protein isn't just an oxygen carrier; it also regulates vascular tone and inflammation by its redox coupling with methemoglobin (HbFe(III)). Methemoglobin's oxidized form, Fe (III), possesses the potential to produce water from oxygen as a free energy reaction. It functions as a nitrite reductase, regulating the oxygen level in the blood and controlling vascular tone by generating nitric oxide from nitrite, thereby increasing blood flow when oxygenated hemoglobin decreases. If methemoglobin can't be reduced, it leads to the dissociation of tetrameric hemoglobin into αβ dimers, releasing heme and iron into circulation. Methods: The study involved Golden Syrian Hamsters with dorsal skin fold window chambers, observing acute methemoglobin effects via hypovolemic infusion (10% of the animal’s blood volume) compared to human hemoglobin and a lactated ringer's control. Microhemodynamics, mean arterial pressure, heart rate, blood gases, and blood properties were measured. Results: Methemoglobin did not significantly affect MAP and HR but increased arteriole diameters by 5% and venule diameter by 15% compared to baseline. However, it caused a 50% reduction in functional capillary density compared to baseline, alongside significant cardiac and kidney inflammation. Conclusion: The study concludes that a hypovolemic infusion of methemoglobin induces vasoreactivity but results in poor microcirculatory pressure and inflammation in vital organs. This demonstrates the delicate balance and potential adverse effects associated with alterations in the hemoglobin redox state and highlights the importance of maintaining its balance for vascular and organ health. Project number: R01HL159862 Project number: R01HL162120. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Potential Role of Diabetes in Impaired Semaphorin-Mediated Maintenance of Epithelial Barrier Properties
Authors: Caceres Paulo 
Published: May 2024

Microvasculature-secreted factors create a local niche for tissue specialization and homeostasis. Diseases like diabetes are considered a microvascular disease. However, the consequences of microvascular alteration in surrounding tissues like epithelial barriers have not been suffciently explored. The objective of this study is to determine whether a cell-cell communication protein, Semaphorin-3E (Sema3E), which we have previously found increased in diabetic mice and in endothelial cells cultured on high glucose, impairs the barrier properties of epithelial cells. We determined by ELISA that HUVEC endothelial cells secreted Sema3E (7.8 ±1.8 pg/sq.cm/day) and while mannitol osmolality control 15mM had no effect, high glucose (25mM) increased Sema3E secretion 6-fold (ANOVA, p<0.01). To test the effect of Sema3E in the tight junction barrier properties of epithelial cells, we measured trans-epithelial electrical resistance (TEER) in Calu-3 epithelial cells cultured in trans-well permeable support. We found that 200ng/ml of recombinant Sema3E inhibited the acquisition of TEER over the course of 2 weeks (vehicle: 803 ± 31 Ω/cm^2 vs. Sema3E: 465 ± 15 Ω/cm^2; t-test p<0.01) The weakening of tight junctions was due to decreased presence of Claudin-2 at the cell surface as measured by surface biotinylation (Surface/intracellular ratio= vehicle: 0.356 ± 0.043 vs. Sema3E: 0.020 ± 0.003; t-test p<0.01). Consequently, the polarity of Calu-3 cells was also impaired as we determined by measuring the polarized distribution of the basolateral protein E-cadherin. We observed a reduction of basolateral E-cadherin from 88 ± 3% (vehicle) to 65 ± 6% (Sema3E), t-test p<0.05. Finally, to determine whether surface Claudin-2 expression was decreased in epithelial cells of diabetic mice, we performed surface biotinylation in freshly isolated kidney renal tubules. We observed that the surface/intracellular ratio of Claudin-2 was decreased by 76% in kidney tubules from type-1 diabetic mice (Akita strain), compared to healthy control mice (control: 4.23 ± 1.44 ratio vs. Akita: 1.03 ± 0.16 ratio, t-test p<0.05). We conclude that glucose stimulates Sema3E secretion from endothelial cells, and this signal protein impairs the epithelial barrier properties of epithelial cells by reducing Claudin-2 presence at tight junctions. Reduced surface Claudin-2 may be a feature of diabetic epithelial cells. American Heart Association NIH. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Mammalian target of rapamycin mediates expression and activity of ADAM 17 in diabetic kidney disease
Authors: Mack James , Faiz Najwa , Abraham Sachin , Ford Bridget 
Published: May 2024

Purpose: Previous data have illustrated a role for the matrix metalloprotease A Disintegrin And Metalloprotease 17 (ADAM17), known to cleave growth factors and cytokines, in renal cell injury in diabetes. The goal of this study was to identify upstream regulators of ADAM17 in the cascade of events contributing to extracellular matrix accumulation in diabetic nephropathy. Rationale: Diabetic kidney disease is a serious complication faced by type 1 and type 2 diabetic patients alike. Albuminuria and extracellular matrix accumulation are prominent features of the disease and this accumulation of extracellular matrix is a contributing factor to renal fibrosis and decline in renal function. The mechanisms involved in the pathogenesis of diabetic kidney disease have not been completely identified. Methodology: Age and weight-matched Sprague Dawley rats were obtained from Harlan Laboratories (Indianapolis, IN). Type 1 diabetes was induced through tail vein injection of streptozotocin. After rats were determined to be diabetic by blood glucose measurement, rapamycin treatments were administered intraperitoneally for two months. Both kidneys were removed and frozen in liquid nitrogen for microscopy and experimental analyses or formalin fixed for morphometric imaging at the experimental endpoint. Kidney cortex homogenates were used for western blot analyses and enzymatic activity assays. Findings: Using the mTOR complex 1 inhibitor rapamycin, it was determined that increased ADAM17 enzymatic activity and ADAM17 protein expression is dependent on mTORC1 in streptozotocin-induced type 1 diabetic rats. Inhibition of mTORC1 with rapamycin abrogated the increase in collagen IV α 2 protein expression observed in diabetic rat cortex. Additionally, this study is the first to provide evidence that mTOR complex 1 activates ADAM17 contributing to extracellular matrix accumulation in diabetic nephropathy. Studies are continuing looking at the molecular mechanisms involved in mTOR activation of ADAM17 resulting in downstream effects in cultured human proximal tubular epithelial cells. Research reported in this poster was supported by the University of the Incarnate Word Offce of Research and Graduate Studies. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Comparison of MYOCYTER and MUSCLEMOTION in the analysis of Induced Pluripotent Stem Cell Derived Cardiomyocyte Contractility
Authors: Anfinson Melissa , Liang Huan-Ling , Kodgi Suraksha , Atkinson Grant , Li Irene , Mitchell Yukiko , Holland Hayden 
Published: May 2024

Patient-specific induced pluripotent stem cells (iPSCs) differentiated into cardiomyocytes (CMs) offer tremendous opportunities for cardiac disease modeling and advancements in precision medicine. There is a need for technologies that allow noninvasive and precise measurements of CM function, such as contractility, to increase throughput for drug screening and testing efforts. Hypoplastic Left Heart Syndrome (HLHS) is a rare and complex congenital heart defect characterized by hypoplasia of the left ventricle, proximal aorta, as well as stenosis or atresia of the mitral and/or aortic valves. Previously it was demonstrated that iPSC-CMs from an HLHS patient with a genetic variant in the alpha myosin heavy chain ( MYH6 gene) exhibited an impaired cardiomyocyte phenotype (dysmorphic sarcomere structure, compensatory expression of MYH7, and altered contractility). Gene editing using CRISPR/Cas9 rescued the phenotype, demonstrating the utility of MYH6 iPSC-CMs as a useful disease model for HLHS. Critical parameters of CM function include contraction and relaxation, assessing systolic and diastolic dysfunction, respectively, in iPSC-CMs. The aim of this study is to compare features from two open-source macros for ImageJ: MYOCYTER and MUSCLEMOTION. MYOCYTER improves upon previous plugins available by allowing for users to select parameters. Both methods allow measurement of movement from high-speed movies. MYOCYTER enables the user to select an optimal threshold, size, and cell count to minimize disturbances such as cellular fragments, background noise, and floating bubbles, to maximize precision during analysis. MUSCLEMOTION allows rapid and easy measurement of movement from high- speed videos and can measure and compare relative or absolute parameters. This study will determine whether a systolic or diastolic dysfunction phenotype is observed under different magnification settings and evaluate the effect of dosing with pharmaceutical compounds. Finally, benefits and drawbacks of both macros will be investigated. Children's Research Institute. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Programming of neutrophil transcriptome by endothelial ERG maintains anti-inflammatory vascular niche in the lungs
Authors: Vellingiri Vigneshwaran , BR Vijay Avin , Joshi Jagdish Chandra , Akhter Zahid , Anwar Mumtaz , Banerjee Somenath , Pinho Sandra 
Published: May 2024

Neutrophils, the predominant blood leukocyte and first responders to the infection, reside as the marginated pool in the lungs. Vascular hyperpermeability and activation of infiltrating neutrophils is the hallmark of lethal acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). However, signaling nodes that govern crosstalk among these ontologically distinct cell types to maintain tissue homeostasis remain unclear. Here, we identify the ERG transcription factor, which maintains endothelial cell (EC) lineage, as the instructor of anti-inflammatory neutrophils. We show that ERG is highly expressed in lung EC, but the expression was reduced markedly during neutrophilic injury by bacterial pneumonia. Intravital imaging and FACS analysis of mice lungs conditionally lacking ERG in the endothelium (iEC-ERG−/−mice) showed increased neutrophil retention and activation due to rewiring of their transcriptome (hereafter referred to as EC-ERG null neutrophils). RNA sequencing of EC-ERG null neutrophils showed genes enriched with inflammation (IL-1β, TNF-α, MIP-2α), survival (RelB, CD47), and retention (CXCR4) markers. Neutrophils isolated from the blood of ARDS patients similarly showed increased expression of IL-8, TNF-α, and CXCR4 expression. EC-ERG null neutrophils induced lung injury when adoptively transferred into a naïve mouse. EC-ERG loss elicited an immune migratory and chemotactic program by activating the NF-κB-IL8 cascade, exacerbating ALI in a mouse model. We show that ERG in endothelium preserves neutrophil activation and infiltration by upregulating the multipurpose deubiquitinase A20 expression in mouse and human lung endothelial cells (EC). Rescuing A20 deubiquitinase or suppressing IL8-CXCR2 axis through small molecule inhibitor, Reparixin, reversed hyperpermeability, and neutrophilic injury. In summary, our study identifies specialized ERG-instructed anti-inflammatory ‘immune niche’ to prevent neutrophilic inflammation and lung injury. National Institutes of Health (NIH) Grants HL060678, HL084153. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Cortical Sources And Autonomic Nervous System Response Of Listening To North Indian Classical Music
Authors: Sahoo Abhisek , Tayade Prashant , Muthukrishnan Suriyaprakash , Kaur Simran , Sharma Ratna , Nayyar Madhavi 
Published: May 2024

BACKGROUND: Music can affect the human brain and qEEG with its sub-second resolution can be used to study brain activity. The North Indian classical music’s (NICM) effect on brain activity is largely undiscovered. OBJECTIVE: To find out the cortical sources activated along with the autonomic nervous system response while listening to NICM. Methods: 30 Indian subjects (Mean age- 26.1 and (SD) - 1.4 years) were asked to listen to 4 NICM ragas of 5 minutes each with increasing minor note to major note ratio i.e., M1(0), M2(0.16), M3(0.4), M4(1.33).128 channel of EEG signal was recorded which was preprocessed and cortical source localization was done using sLORETA.The autonomic nervous system response while listening to each music excerpt was assessed using Heart Rate Variability parameters by measuring lead II electrocardiography. RESULTS: The cortical sources analysis showed increased activation in cortical regions associated with the extraction of acoustic features of music (superior, middle, and inferior temporal gyruses in addition to fusiform and supramarginal gyrus), emotion generation (precuneus and inferior frontal gyri) and Default Mode Network (posterior cingulate cortex, medial prefrontal cortex, and inferior parietal lobule) while listening to M1. There was a decreased activation in these areas while listening to M2, M3 & M4 (as the minor notes increased).The mean heart rate was significantly higher while listening to M4. There was a reduction in HF while listening to M4 and M3.There was a significant decrease in RMSSD while listening to M4 as compared to the resting state. CONCLUSION: Music can affect brain activity and autonomic function. Music with major notes causes activation of DMN areas causing mind wandering and self-referential mental activity than music with minor notes which decreases DMN activity.In terms of autonomic function increase in minor notes caused decrease in RMSSD and HF signifying an increase in stress and reduced parasympathetic tone. The authors declare no competing interest. The study was approved by the Institutional Review Board (IRB). No Grant was used. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Renal Intercalated cells: allien cells inside us?
Authors: Graciano Miguel 
Published: May 2024

Mammalian renal intercalated cells (ICs) are known for their role in acid secretion and acid- base regulation. Based on previously published data, we discussed the theoretical reasons behind the development of additional renal IC biology characteristics, tracing them back phylogenetically to the simplest animals and protozoa. ICs have the following additional functions or attributes: (1) they play immunological roles in protecting the kidneys against both infective and aseptic kidney damage; (2) they are energized by V-ATPases in a similar fashion to protozoa; (3) they possess a T-antigen that is common in embryonic and cancer cells, which confers invasiveness ability to those cells; and (4) they exhibit plasticity and the ability to regenerate other epithelial cells (i.e., they exhibit stem cell behavior). Renal ICs may derive from amoeboid cells sharing these characteristics that originated from an evolutionary line that includes protists, or even the Last Eukaryotic Common Ancestor (LECA). None. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Lysophosphatidic Acid Receptor 3 Activation Is Involved in the Regulation of Erythrocyte Differentiation Through Ferroptosis
Authors: Huang Yi-Xun , Lee Hsinyu 
Published: May 2024

Ferroptosis, a unique form of programmed cell death trigged by lipid peroxidation and iron accumulation, has been implicated in embryonic erythropoiesis and aging. Our previous research demonstrated that lysophosphatidic acid receptor 3 (LPA3) activation mitigated oxidative stress in progeria cells and accelerate the recovery of acute-anemia in mice. Given that both processes involve iron metabolism, we hypothesized that LPA3 activation might mediate cellular ferroptosis. In this study, we used LPA3 agonists 1‐Oleoyl‐2‐O‐methyl‐rac‐glycerophosphothionate (OMPT) to activate LPA3 and examine its effects on the ferroptosis process. OMPT treatment elevated anti-ferroptosis genes protein expression, including solute carrier family 7 member 11 (SLC7A11), glutathione peroxidase 4 (GPX4), heme oxygenase-1 (HO-1), and ferritin heavy chain (FTH1) in erastin-induced cells. Furthermore, OMPT reduced lipid peroxidation and intracellular ferrous iron accumulation, as evidenced by C11 BODIPYTM 581/591 Lipid Peroxidation Sensor and FerroOrange staining. These observations were validated by applying LPAR3 siRNA in the experiments mentioned above. In addition, the protein expression level of nuclear factor erythroid 2-related factor (NRF2), a key regulator of oxidative stress regulator, was also enhanced in OMPT treated cells. Lastly, we verified that LPA3 plays a critical role in erastin-induced ferroptotic human 25 erythroleukemia K562 cells. OMPT rescued the erythropoiesis defect caused by erastin in K562 cells through using Gly A promoter luciferase assay. Taken together, our findings suggest that LPA3 activation inhibits cell ferroptosis by suppressing lipid oxidation and iron accumulation, indicating that ferroptosis could potentially serve as a link between LPA3, aging and erythropoiesis. MOST 110-2311-B-002-026 MOST 111-2311-B-002-007. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.