bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of Cytotoxic Chemotherapy and Endocrine Therapy on Hemodynamics and Oxygen Uptake During Handgrip Exercise in Patients Treated for Breast Cancer
Authors: Kofoed Jason , Borrelli Marta , Bisconti Angela Valentina , Craig Jesse , Laginestra Fabio , Colonna Sarah , Buys Saundra 
Published: May 2024

Breast cancer therapies can alter skeletal muscle blood flow during exercise and decrease mitochondrial content and function. However, the impact of different therapies on the variables determining oxygen transport and utilization during submaximal exercise remain unknown. We tested the hypothesis that both chemotherapy and endocrine therapy would decrease blood flow and increase deoxygenated [hemoglobin+myoglobin] (HHb) with an unchanged oxygen uptake (VȮ2) during exercise compared to healthy controls. Participants were healthy females (CTRL; n = 5; age: 58 ± 8 years; body mass index: 25 ± 4 kg/m2) or female patients diagnosed with stage I-III breast cancer comprising three groups: 1) two to five weeks post completion of cytotoxic chemotherapy (CHEMO; n = 5; age: 55 ± 8 years; body mass index, BMI: 30 ± 4 kg/m2); 2) currently on endocrine therapy ≥5 months (ENDO; n = 9; age: 59 ± 7 years; BMI: 27 ± 6 kg/m2); and 3) completed cytotoxic chemotherapy and currently on endocrine therapy ≥5 months (CHEMO+ENDO; n = 8; age: 58 ± 6 years; BMI: 26 ± 5 kg/m2). Forearm blood flow, HHb, and estimated VȮ2 were measured during the final minute of a 3-minute intermittent isometric handgrip exercise at 3 and 6 kg. There were no group or group x intensity effects (all p<0.18) for forearm blood flow (CTRL: 260 ± 33 ml/min; CHEMO: 407 ± 96 ml/min; ENDO: 309 ± 140 ml/min; CHEMO+ENDO: 313 ± 86 ml/min), HHb (CTRL: 134 ± 58 μM; CHEMO: 73 ± 36 μM; ENDO: 118 ± 67 μM; CHEMO+ENDO: 101 ± 25 μM), or estimated VȮ2 (CTRL: 59 ± 28 ml/min; CHEMO: 48 ± 21 ml/min; ENDO: 54 ± 28 ml/min; CHEMO+ENDO: 53 ± 21 ml/min). These findings indicate that chemotherapy and endocrine therapy do not affect muscle hemodynamics and oxidative metabolism during submaximal handgrip exercise. This study was funded, in part, by the Veterans Affairs Clinical Science Research and Career Development Award (IK2 CX002114). 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.
Mitochondrial peptides derived from exercising skeletal muscle increase oxidative stress in microvascular endothelial cells
Authors: Hansen Camilla Collin , Gudiksen Anders , Van der Stede Thibaux , Frisch Nicklas , Rol Josephine M. , Jung Jens , Hoier Birgitte 
Published: May 2024

Introduction: Mitochondria-derived peptides are newly discovered small bioactive peptides thought to communicate metabolic status to other cells. Two such peptides, MOTS-c and Humanin, have been shown to have particularly strong local and systemic regulatory effects on metabolism and oxidative stress in tissues, but their effect specifically on vascular endothelial cells remains unclear. Furthermore, it has been proposed that skeletal muscle is a source of MOTS-c and humanin during exercise but this has not been directly shown. Methods: In seven healthy young males, muscle interstitial fluid was collected from microdialysis probes in the thigh muscle, blood was drawn from femoral arterial and venous catheters and thigh muscle biopsies were obtained before and after one acute bout of exercise. In addition, muscle biopsies were obtained before and after 14 days of leg exercise training. Samples were analysed for MOTS-c, Humanin protein and mRNA. To test the effect of MOTS-c on the microvasculature, human endothelial cells derived from the muscle biopsies were incubated for three days with MOTS-c and analysed for mitochondrial respiration and formation of reactive oxygen species (ROS). Furthermore, mice were injected with MOTS-c for 4-weeks to investigate the in-vivo effect of vessels and microvascular endothelial cells. Data was analyzed by linear mixed models performed with R. Results: Acute exercise resulted in an 88% and 55% ( p<0.001) increase in MOTS-c and humanin concentration, respectively, in muscle dialysate, with no effect on the femoral arterial-venous plasma concentration differences. Both MOTS-c and humanin mRNA levels increased (by 20 and 26%; p<0.05) after acute exercise and were 43% and 35% ( p<0.05) higher, respectively, after 14 days of training. A period of MOTS-c treatment of endothelial cells increased mitochondrial respiration and ROS formation by 3-fold and 5-fold, respectively ( p<0.01). Muscle derived endothelial cells from mice injected for 4-weeks presented a similar mitochondrial respiration but a 4-fold ( p<0.05) higher ROS emission. Conclusion: interstitium in response to exercise, muscle is not a likely source of these peptides in plasma. Our data from in vitro and in vivo experiments suggest that treatment with MOTS-c does not influence endothelial metabolism but leads to increased oxidative stress in microvascular endothelial cells. The funding by Novo Nordisk Foundation (application number: 0070369) is gratefully acknowledged. 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.
Metabolic Function of Leucine-Rich Repeat Transmembrane Neuronal 4 Expressed by Hypothalamic AgRP Neurons
Authors: Kim Seungjik , Ko Jaewon , Sohn Jong-Woo 
Published: May 2024

It is well known that the agouti-related peptide (AgRP)-expressing neurons of the arcuate nucleus of the hypothalamus regulate energy balance and glucose homeostasis. While it was previously shown that excitatory and inhibitory synaptic input onto the AgRP neurons influence the activity and metabolic function of AgRP neurons, little is known about the role of synaptic adhesion molecules therein. In this study, we focused on a synaptic adhesion molecule, leucine-rich repeat transmembrane neuronal 4 (LRRTM4), which is expressed by post-synaptic part of excitatory synapses to be involved in synapse formation and synaptic transmission. We generated conditional knockout mice which lacks LRRTM4 specifically in the AgRP neurons, and assessed the electrophysiological and metabolic phenotypes. Our results should provide insight how synaptic machinery of hypothalamic AgRP neurons can shape in vivo metabolic function. This work was supported by the National Research Foundation of Korea (NRF-2022R1A2C3005613 to Jong-Woo Sohn) funded by the Korean Ministry of Science and ICT. 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.
Role of Dorsal Raphe Serotonergic Neurons in the Regulation of Sodium Appetite
Authors: Shin Yurim , Kim Seungjik , Sohn Jong-Woo 
Published: May 2024

An animal with sodium deficiency develops sodium appetite which drives it to consume more sodium. A lot of studies have been performed to understand how sodium depletion may lead to the development of sodium appetite, but there are still unanswered questions. In particular, while the relationship between serotonin receptors and sodium appetite has been identified in previous studies, it is still unclear how serotonergic neurons control sodium appetite in response to sodium depletion. In this study, we focused on serotonergic neurons in the dorsal raphe nucleus (DRN) which releases more than 50% of serotonin in the brain. We found that DRN serotonergic neurons are activated in response to sodium depletion. In addition, we found evidence that angiotensin II is a key molecule herein to evoke sodium appetite in sodium depletion. Our results provide refined insight how sodium appetite develops in sodium depletion. This work was supported by grants from Samsung Science & Technology Foundation (SSTF-BA1901-11) to Jong-Woo Sohn. 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.
Insulin and glucose tolerance assessment in guanylyl cyclase/natriuretic peptide receptor-A gene-targeted mutant mice
Authors: Neelamegam Kandasamy , Ramasamy Chandramohan , Pandey Kailash N. 
Published: May 2024

Atrial natriuretic peptide (ANP), acting through guanylyl cyclase/natriuretic peptide receptor-A (GC-A/NPRA) regulates blood pressure and cardiac homeostasis. The disruption of Npr1 (encoding NPRA) in mice exhibits hypertension and provokes renal and cardiac disorder. However, the underlying mechanisms are not yet precisely determined. The objective of this study was to determine whether Npr1 plays a role in regulating glucose homeostasis in global Npr1 gene-disrupted mice. The adult male (14-18 wks) Npr1 haplotype gene-knockout ( Npr1+/-, 1-copy), wild-type ( Npr1+/+, 2-copy), and gene-duplicated ( Npr1+ +/+ +, 4-copy) mice were fasted overnight (16 h) and given free access to water. The mice were administered with glucose both orally and intraperitoneally (2 g/kg body weight) to determine the oral glucose tolerance test (OGTT) and intraperitoneal glucose tolerance test (IPGTT). For the insulin tolerance test (ITT), mice were also fasted for 16 h and then received an ip-injection of insulin (1.0 UI/kg body weight). Blood glucose levels were determined by performing tail bleeds at 0, 15, 30, 60, 90, and 120 min using the AlphaTRAK blood glucose monitoring system. The results showed that administration of glucose resulted in a greater increases in blood glucose levels at 120 mins in 1-copy mice (OGTT: 237 ± 5 mg/dL, IPGT: 246 ± 6 mg/dL, ITT; 239 ± 7 mg/dL) than 2-copy male (OGTT: 131 ± 3 mg/dL, IPGT: 126 ± 6 mg/dL, ITT; 127 ± 6 mg/dL), respectively. The blood glucose was also significantly lower in 4-copy mice (OGTT: 113 ± 5 mg/dL, IPGT: 108 ± 7 mg/dL, ITT; 107 ± 3 mg/dL) than in 2-copy mice. Systolic blood pressure (SBP) was determined by non-invasive tail-cuff method (Visitech 2000). SBP was significantly greater in 1-copy mice (130 ± 4 mmHg) than 2-copy mice (100 ± 3 mmHg). Similarly, SBP was also significantly lower in 4-copy mice (90 ± 2) than 2-copy mice. The increase in plasma glucose levels was significantly lower in OGTT than in IPGTT. The present results suggest that decreased Npr1 gene copy number predisposes to hyperglycemia, insulin resistance, and hypertension. These results indicate that the Npr1 gene might regulate blood glucose homeostasis. This work was supported by the NIH grant (DK133833). 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.
Evaluating Physiological and Organizational Properties of the Tight Junction ZO-1 ZU-5 Domain in MDCK Cells
Authors: Holloway Cristian , Palmer Garrett , Cooper Joshua , Eis Ainsley , King Jonathan 
Published: May 2024

Zonula occludens-1 (ZO-1) is an essential TJ component contributing to junctional formation by mediating interactions between junctional proteins and the actomyosin cytoskeleton. MDCK II cells, a model epithelial cell line, with ZO-1 knocked-out (ZO-1 KO) have observable phenotypic changes such as alterations in the actin cytoskeletal organization and physiological barrier properties. This study focuses on the ZO-1-ZU5 domain by rescuing ZO-1 with full-length and a panel of ZO-1-ZU5 mutants. ZO-1-ZU-5 is known to bind cingulin and through this interaction ZO-1 adopts an extended conformation. We examined actomyosin cytoskeleton organization, ZO-1 mobility, gene expression and barrier function to determine whether the ZO-1-ZU5 mutants rescue full-length activity. We found that the ZO-1- ZU5 truncation mutant cell line rescued transepithelial electrical resistance (TER) but did not rescue tight junction distribution or the amount of total gamma-actin. We will present evaluation of additional ZU5 mutants. This study expands our understanding of how extended ZO-1 regulates the mechanical, genetic, and phenotypic properties of epithelial cells. Trinity University Biology Summer Undergraduate Research Fellowship. 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.
Intermittent Fasting Causes Sex-Specific Effects On Metabolic Switching And Aortic Inflammation In A Mouse Model Of Diet-Induced Metabolic Syndrome
Authors: Tran Vivian , Wickramasinghe Buddhila , Jamal Abdulsatar , Hughes Tayla , Diep Henry , Dinh Quynh Nhu , Sobey Christopher G 
Published: May 2024

Metabolic syndrome (MetS) is a complex multifactorial disease that increases the risk for cardiovascular disease. Despite various treatment strategies, such as restrictive caloric intake and drug therapies, MetS remains challenging to manage. Intermittent fasting (IF) has been proposed as an alternative to traditional treatment as a means of MetS management. However, the sex-specific responses to intermittent fasting during MetS are unclear. Using a mouse model of diet-induced MetS, we characterised the sex-specific effects of IF on metabolic disturbances and aortic inflammation. Six-week-old male and female C57BL/6 mice were fed either a high-fat diet (43% kcal) with high-sugar and high-salt (10% high-fructose corn syrup and 0.9% NaCl in drinking water; HFSS), or normal control diet (NCD). After 10 weeks, mice were randomly assigned to ad libitum (AL) feeding or IF (16 hours/day) for 10 weeks. Physiological parameters were measured during the diet regime and aortic inflammation was measured at endpoint using flow cytometry. HFSS feeding increased bodyweight and fasting blood glucose in both sexes ( P < 0.05), which were reversed by IF irrespective of diet or sex ( P < 0.05). IF increased fasting blood ketones in HFSS-fed females (vs. HFSS-AL females; P < 0.05), but not in HFSS males. Despite HFSS-induced MetS in both sexes, aortic proinflammatory monocytes (CD11b+Ly6CHi), patrolling monocytes (CD11b+Ly6CLo) and macrophages (CD11b+F4/80+) were increased in males mice only. IF reduced proinflammatory monocytes and macrophages in HFSS-IF males as well CD4+ and CD8+ T cells (vs. HFSS-AL males, P<0.05). In summary, IF improved HFSS-induced metabolic disturbances in both sexes, yet metabolic switching (ketosis) was only observed in females. Moreover, HFSS induced aortic inflammation in males only, highlighting the sexual dimorphisms in vascular inflammation during MetS. Our study is the first to report that intermittent fasting reduces aortic inflammation in metabolic syndrome. Further studies are underway to determine the downstream effects of aortic inflammation on end-organs such as the kidneys and liver. National Health and Medical Research Council, Graduate Women Victoria, The Jack Brockoff Foundation. 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.
Blood Glucose Fluctuation Is Indicative of Adiposity
Authors: Apaflo Jehu , Sanders Ka'Delyn , Labadah Joshua , Narvaez Gabriel , Rocha Victoria , Villalobos Ulices , John Tomy Irene 
Published: May 2024

Introduction: Continuous glucose monitoring (CGM) system is an effective tool for assessing a person’s glycemic control in real-time, in a “free living condition”. Poor glycemic control is strongly linked to cardiovascular disease, obesity, and the pernicious deposition of fat in the abdominal region. Emerging data show that surges in glucose levels after a meal (postprandial glucose excursions) are more tightly linked to cardiovascular disease, insulin resistance, and diabetic complications than the traditional clinical measure of glycemic control using glycated hemoglobin (HbA1c). Therefore, the purpose of this study is to determine if daily glycemic variability as measured by CGM is an indicator of total and regional body fat distribution and how CGM compares with HbA1c measurements. Methods: Twenty-seven volunteers participated in the study (Male: 11, Female: 16, Age: 32.15 ± 14.55 years, BMI: 28.43 ± 7.30 kg/m2). Total body and regional fat distribution (android, gynoid, android/gynoid) were determined using dual-energy x-ray absorptiometry. Fasting blood glucose and glycated hemoglobin (HbA1c) were measured from collected blood samples. Glycemic variability was measured by CGM attached to the abdomen. Results: CGM glycemic variability was positively correlated with total body fat% (r= 0.4278; p= 0.0329), android fat% (r= 0.5313; p= 0.0063), and android/gynoid ratio (r= 0.5981; p= 0.0016). HbA1c was only positively correlated with android/ gynoid ratio (r= 0.5534; p= 0.0041). Conclusion: Higher blood glucose variability/fluctuation measured by CGM was associated with greater body fat, android fat, android/gynoid fat ratio, which are indicators of cardiovascular disease risks. Blood glucose fluctuation monitoring should be considered in blood glucose management. This study was funded by The University of Texas, El Paso Dodson Fund and the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health (NIH) - R01DK132430. 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.
Comparative Study of Men and Knock-in Mice Expressing Red Cell Glycophorin B-A-B hybrid Protein Identifies Physiological Functions of SLC4A1 (band 3)
Authors: Hsu Kate , Chen Li-Yang , Chen Pin-Lung 
Published: May 2024

GP.Mur is a common Southeast Asian red blood cell (RBC) type, with 4.7% prevalence in Taiwan (compared to 5.8% AB blood type). In people with the GP.Mur (glycophorin B-A-B hybrid) type, their expression of Cl−/HCO3− anion exchanger-1 (AE1; SLC4A1; band 3) on the RBC membrane is increased. Glycophorin A, as well as this glycophorin B-A-B variant, are chaperone proteins that promote SLC4A1 folding and protein formation by 10% or more. Healthy people with the GP.Mur blood type exhibit two unique physiological features: (1) slightly higher blood pressure, and (2) more effcient CO2 excretion. Human and mouse lacking SLC4A1 cannot survive postnatally. As the physiological impacts and mechanisms of SLC4A1 are unclear, we created a knock-in mouse model of human GYP.Mur. To verify whether these physiological features could indeed be the direct consequences of GYP.Mur expression, we tested the knock-in mice by (1) blood pressure measurements with antihypertensive drug challenges, and (2) whole-body plethysmorgraphy (WBP)-respiration measurements. We found that GYP.Mur knock-in mice also expressed more SLC4A1 on the RBC membrane. The knock-in mice exhibited significantly higher mean arterial pressure (MAP) than age-matched control C57BL/6J mice, with differential antihypertensive sensitivities. In WBP measurements on freely-moving mice, GYP.Mur knock-in and the control mice also showed differential respiratory patterns, which were diminished with acetazolamide pretreatments. Thus, GYP.Mur knock-in mice recapitulates the major phenotypes of people carrying the GP.Mur blood type. Taiwan Ministry of Science & Technology (MOST 108-2628-B-195-001; 109-2628-B-195-001; 110-2628-B-195-001); Taiwan MacKay Memorial Hospital. 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.
The In Vitro Effect of Kynurenine Metabolites on Cell morphology, Cell cycle progression and the Induction of Apoptosis in Tumour Endothelioma Cells
Authors: Tatchum Sandra , Joubert Annie , Serem June , Bipath Priyesh , Nyakudya Trevor , Hlophe Yvette 
Published: May 2024

Background: Cancer is one of the leading causes of death worldwide. The development of anticancer therapies plays a crucial role in mitigating tumour progression and metastasis. Kynurenine metabolites which include L-kynurenine, 3-hydroxykynurenine, 3-hydroxyanthranilic acid and quinolinic acid have been shown to inhibit T-cell proliferation resulting in a decrease in cell growth of natural killer (NK) cells and T cells. Research showed that L-kynurenine inhibits proliferation of melanoma cells in vitro. Methods: The present study aimed to explore the in vitro influence of L-kynurenine, quinolinic acid and kynurenic acid on endothelioma sEnd-2 cells at concentration ranges of 1 mM – 4 mM for 24 h, 48 h and 72 h on cell morphology, cell cycle progression and induction of apoptosis. Results and Discussion: The half inhibitory concentration (IC50), as determined using GraphPad Prism, for L-kynurenine, quinolinic acid and kynurenic acid was 10.77 mM, 14.78 mM and 535.40 mM respectively. Optical transmitted light differential interference contrast and hematoxylin and eosin staining revealed the presence of cells blocked in metaphase, formation of apoptotic bodies and compromised cell density in L-kynurenine- and quinolinic acid- treated cells. A statistically significant increase in the number of cells present in the sub-G1 phase was observed in L-kynurenine-treated samples. Conclusion: It can be concluded that L-kynurenine exerts an antiproliferative effect on the sEnd-2 cell line by a decrease in cell growth and proliferation and metaphase block. These hallmarks suggest cell death via apoptosis. Further research will be conducted on L-kynurenine to assess the effect on cell adhesion in vitro and in vivo. This research was supported by the following grants: The Research Development Programme at the University of Pretoria awarded to Dr YN Hlophe; National Research Foundation awarded to Dr YN Hlophe (A1F4685 & N1F580); The University Capacity Development Programme (UCDP) awarded to Ms Tatchum (A1D783 & N1F120). 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.