bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of spermidine on endothelial function in Systemic Lupus Erythematosus (SLE)
Authors: Kim Hyoseon , Nino Matthew , Massett Michael 
Published: May 2023

Impaired endothelial function has been shown in SLE patients and lupus-prone mice. Emerging evidence supports impaired mitochondrial dynamics and mitophagy contribute to SLE and endothelial dysfunction. Spermidine is a natural polyamine that stimulates mitophagy by activating the PINK1-Parkin pathway and can improve endothelial function. However, the effect of spermidine on mitophagy and vascular function in SLE has not been explored. To address this gap, 9-week-old female lupus-prone (MRL/lpr) and healthy control (MRL/MpJ) mice were randomly assigned into one of two groups, spermidine treatment (Lpr T and MpJ T) or control (Lpr C and MpJ C). Treated mice received spermidine (3mM) via drinking water for 8 weeks. After 8 weeks of treatment, endothelium-dependent vasorelaxation to acetylcholine (ACh) and endothelium-independent vasorelaxation to sodium nitroprusside (SNP) were measured in thoracic aortas using a wire myograph. Maximal responses to ACh were significantly impaired in Lpr C (67.1 ± 8.7, n = 11) compared to Mp C (90.3 ± 3.1, n = 13) (p = 0.01). Spermidine improved endothelial function in thoracic aorta from Lpr T (90.3 ± 2.8, n = 13) compared to Lpr C (p = 0.03). Maximal responses to SNP were not significantly different across the groups. Thoracic and abdominal aortas were used for measurements of protein content (n = 3-4/group) and gene expression (n = 4/group), respectively. There were strain differences in the mRNA expression of endothelial nitric oxide synthase ( Nos3) between Lpr C (0.65 ± 0.14) and MpJ C (1.00 ± 0.16) (p = 0008). In MpJ mice, Nos3 mRNA expression was significantly higher in the aorta from the MpJ T (1.47 ± 0.39) compared to MpJ C (p = 0.04). No significant differences were found in the Nos3 expression between Lpr groups. Vascular cell adhesion molecule 1 (Vcam1) is an indicator of inflammation and is associated with atherosclerosis susceptibility. Protein content of Vcam1 was significantly lower in Lpr T (3.73 ± 0.61) compared to Lpr C (8.49 ± 2.58) (p = 0.04) and gene expression of Vcam1 was also lower in Lpr T compared to Lpr C, suggesting spermidine decreases the inflammatory responses in vessels from SLE mice. Protein content of Parkin was measured as a marker of mitophagy. Parkin was significantly lower in Lpr C (0.38 ± 0.61) compared to MpJ C (1.00 ± 0.09) (p = 0.004), suggesting lower mitophagy in aorta from SLE mice. Parkin content in Lpr T was similar to MpJ C. Collectively, these results demonstrate the beneficial effects of spermidine treatment on endothelial function in SLE mice and suggest inflammation and altered mitophagy contribute to endothelial dysfunction in SLE. This is the full abstract presented at the American Physiology Summit 2023 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.
Dietary potassium restriction reprograms the distal tubule causing adverse metabolic consequences
Authors: Su Xiao-Tong , Reyes Jeremiah , Cornelius Ryan , Duan Xin-Peng , Wang Wen-Hui , McCormick James , Yang Chao-Ling , Nelson Jonathan , Ellison David 
Published: May 2023

Low potassium (K) intake has adverse health effects, including hypertension, osteoporosis, and nephrolithiasis. Dietary K restriction rapidly activates a K switch in the distal nephron to maintain homeostasis by reducing K excretion and activating the sodium chloride cotransporter (NCC). The distal convoluted tubule (DCT) is morphologically and functionally divided into DCT1 and DCT2, with each segment specialized for a different function. Here, we define the differences between DCT1 and DCT2 transcriptionally, examine their unique responses to potassium restriction, and detrimental physiological responses in mice.The K restriction effects were examined at 3 time points, overnight (acute), 4 days (short-term), and 4 weeks (chronic). Electrophysiology was used to assess effects of acute K deprivation on basolateral K channel (Kir4.1/5.1) activity. To determine effects of K restriction for 4 days, the DCT-targeted single-nucleus RNA-sequencing (snRNAseq) approach was applied. Female NCC-Cre-INTACT (PMID: 26087164) mice were provided either normal (NK) or K deficient (KD) diet for 4 days (short-term) and kidneys were snap-frozen for targeted snRNAseq (10X Chromium, NovaSeq) (3 mice per diet, 10,000 nuclei per mouse). Effects of chronic K-restriction were assessed by serum electrolytes, tissue clearing, and western blot.Acute K restriction stimulated basolateral K channel activity in DCT1, but not in DCT2, indicating that DCT1 and DCT2 respond differently. Although both DCT1 and DCT2 express NCC, snRNAseq data showed that DCT1 and DCT2 have distinct transcriptional signatures, with DCT1 expressing genes involved in magnesium reabsorption, and DCT2 expressing genes involved in calcium reabsorption and electrogenic sodium channel (ENaC). Four days of K restriction switched the DCT from a K-wasting state to K-sparing state, shown by reduction of gENaC ( Scnn1g) and Kallikrein ( Klk1) expression. Furthermore, K restriction decreased the expression of the calcium-handling genes Slc8a1, Calb and Vdr. When prolonged, K restriction led to increases in NCC, reduction in ENaC cleavage, and elongation of the DCT. It also led to calcium wasting (plasma iCa in NK, 1.38 ± 0.03, n=7; KD, 1.24 ± 0.01 mM, n=6) and reduction in calbindin D-28k protein.Our results suggest that DCT1 and DCT2 both express NCC, but have distinct transcriptomic signatures with unique roles in magnesium and calcium transport, respectively. Dietary K restriction reprograms DCT2 cells to be more like DCT1 cells, thereby maintaining K balance but contributing to calcium wasting as a complication. NIH DK51496, NIH DK054983, VA 1I01BX002228, LeDucq Fondation This is the full abstract presented at the American Physiology Summit 2023 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.
Class participation correlates with academic performance in a Biochemistry and Metabolism course for first-year veterinary school students
Authors: Schonhoff Christopher , Cardamone Carie 
Published: May 2023

The objective of the current study was to investigate whether class participation correlates with academic performance in a Biochemistry and Metabolism Course for first-year veterinary school students. Veterinary Biochemistry and Metabolism is a required course for first-year veterinary students at the Cummings School of Veterinary Medicine at Tufts University. The course is a large lecture course with approximately 100 students enrolled each year. Topics covered in the course include the metabolism of carbohydrates, nucleic acids, lipids, proteins, vitamins, and microminerals. In the fall of 2021, students had three options for lecture attendance. Students could attend in person, could listen to lectures streamed live, or could watch lectures at a later time since class sessions were all recorded. To increase engagement in the course, students receive Poll Everywhere questions during most of the lectures in this course. These questions were mainly in multiple-choice format and delivered to students at various times (beginning, middle, and end) during the class. Students who earned A, B, or C grades were compared with how often those cohorts participated in the Poll Everywhere questions. The results indicate that students who earned an A in the course have statistically significant higher participation in Poll Everywhere questions when compared to students who earned a B or C. The results do not distinguish between students who attended the lecture in person and those who watched the live stream since all those students could answer the Poll Everywhere questions during class time. The results demonstrate an association between class participation and academic performance. Namely, higher involvement as measured by answering Poll Everywhere question participation increases the likelihood of getting an A. Many professional schools (medical, dental, and veterinary) routinely record most lectures and do not require attendance. While lecture recordings may provide a valuable study tool for students, these results suggest that students who do not actively engage with class material miss an opportunity to maximize learning. No funding to disclose This is the full abstract presented at the American Physiology Summit 2023 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.
Acute Effect of Intermittent Hypoxia on Peripheral Vascular Function in Older Adults
Authors: Stray-Gundersen Sten , Wojan Frank , Tanaka Hirofumi , Lalande Sophie 
Published: May 2023

Aging is associated with vascular endothelial dysfunction observed through a progressive loss of flow-mediated dilation, which is partly caused by a decreased nitric oxide bioavailability. Continuous exposure to hypoxia, achieved by breathing low levels of oxygen, stimulates nitric oxide production and induces peripheral vasodilation. Intermittent hypoxia, consisting of alternating short bouts of breathing hypoxic and normoxic air, triggers similar physiological responses to chronic hypoxia, but without the detrimental effects often associated with longer hypoxic exposure. The aim of this randomized crossover trial was to determine whether intermittent hypoxia induces brachial artery vasodilation and acutely improves flow-mediated dilation in older adults. Eleven apparently healthy older adults (six women, age: 57±7 years, body mass index: 24.5±3.5 kg/m2) visited the laboratory on two separate occasions. Endothelium-dependent vasodilation was assessed by brachial artery flow-mediated dilation using a semiautomated diagnostic ultrasound system before and 15 minutes after exposure to either intermittent hypoxia (IH) or intermittent normoxia (IN). Intermittent hypoxia consisted of eight 4-min hypoxic cycles at a targeted oxygen saturation of 80% interspersed with breathing room air to resaturation. Air was made hypoxic by titrating nitrogen into a breathing circuit. Intermittent normoxia consisted of eight 4-min normoxic cycles separated by one minute of breathing room air. Hemodynamics, oxygen saturation, and pulmonary gas exchange were continuously assessed during both conditions. By design, intermittent hypoxia resulted in an oxygen saturation of 81±1%, corresponding to an oxygen concentration of 11.4±0.6%. Exposure to intermittent hypoxia, but not intermittent normoxia, elicited a brachial artery vasodilation (IH: 3.61±0.49 to 3.73±0.48 vs. IN: 3.60±0.51 to 3.55±0.50 mm, p=0.01). Brachial artery flow-mediated dilation was not acutely affected by intermittent hypoxia or intermittent normoxia (IH: 5.4±2.0 to 5.5±2.4% vs. IN: 4.8±1.3 to 4.7±2.3%, p=0.17). Intermittent hypoxia did not affect mean arterial pressure (91±6 vs. 92±7 mmHg, p=0.56) but increased heart rate when compared to intermittent normoxia (61±9 vs. 55±9 bpm, p<0.01). In conclusion, exposure to intermittent hypoxia triggered a brachial artery vasodilation but did not immediately affect endothelium-dependent vasodilation in older adults. Repeated exposure to intermittent hypoxia may be necessary to improve endothelial function in this population. This is the full abstract presented at the American Physiology Summit 2023 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.
Finnish Sauna Bathing and Vascular Health of Adults with Coronary Artery Disease: a Randomized Controlled Trial
Authors: Debray Amélie , Gravel Hugo , Garceau Laurence , Bartlett Audrey-Ann , Chaseling Georgia , Ravanelli Nicholas , Barry Hadiatou , Behzadi Parya , Desrosiers-Gagnon Charles , Neagoe Paul-Eduard , Sirois Martin , Nigam Anil , Gagnon Daniel 
Published: May 2023

BACKGROUND: Regular Finnish sauna use has been associated with a reduced risk of cardiovascular mortality. However, physiological mechanisms underlying this association remain unknown. Other forms of heat therapy have been shown to improve markers of vascular health in healthy young adults, middle-aged adults with cardiovascular risk factors, and older adults with chronic heart failure. It is unknown if Finnish sauna use elicits similar adaptations. HYPOTHESIS: This study determined if Finnish sauna bathing improves markers of vascular health in adults with coronary artery disease (CAD). We tested the primary hypothesis that 8 weeks of Finish sauna bathing improves peripheral endothelial function. Secondary hypotheses were that Finish sauna bathing improves peripheral microvascular function, central arterial stiffness and blood pressure. METHODS: Forty-one adults (62 ± 6 years, 29.0 ± 4.3 kg/m2, 33 men/8 women) with stable CAD and na&iuml;ve to heat therapy were randomized to 8 weeks of Finnish sauna use (n=21, 4 sessions/week, 20-30 min/session) or control intervention (lifestyle maintenance, n=20). Peripheral endothelial function (brachial artery flow-mediated dilation, FMD), central arterial stiffness (carotid-femoral pulse wave velocity), total (area under the curve) and peak post-occlusion forearm reactive hyperemia, and blood pressure (automated auscultation) were measured before and after the intervention. RESULTS: Brachial artery FMD changed from 4.09 ± 2.05% to 4.24 ± 2.70% in response to sauna bathing and from 4.00 ± 2.02% to 4.10 ± 2.10% in response to the control intervention (p for interaction = 0.95). The change in central arterial stiffness (p for interaction = 0.82), total reactive hyperemia (p for interaction = 0.07), systolic (p for interaction = 0.95) and diastolic (p for interaction = 0.29) blood pressure also did not differ between interventions. The change in peak reactive hyperemia differed between interventions (p for interaction = 0.05) due to a slight decrease in response to sauna bathing (3.03 ± 1.42 to 2.75 ± 1.18 ml/min/mmHg, p=0.76) relative to a slight increase in response to control (2.78 ± 0.98 to 3.24 ± 1.00 ml/min/mmHg, p=0.05). CONCLUSION: These results demonstrate that 4 sessions of Finnish sauna bathing per week for 8 weeks does not improve markers of vascular health in older adults with stable CAD. Heart and Stroke Foundation of Canada, Fonds de Recherche du Québec – Santé This is the full abstract presented at the American Physiology Summit 2023 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.
Effects of Neuromuscular Electrical Stimulation on Fasting Blood Glucose
Authors: Bajpeyi Sudip , Apaflo Jehu , Narvaez Gabriel , Labadah Joshua , Mossayebi Ali , Rocha Victoria , Jung Hyejin , Wagler Amy , Thyfault John , McAinch Andrew 
Published: May 2023

Muscle contraction during physical activity improves glucose metabolism and glycemic control by facilitating muscle glucose uptake and utilization. Neuromuscular electrical stimulation (NMES) is an involuntary alternative mode of muscle contraction and is widely applicable and suitable for individuals with sedentary lifestyle including people with physical functional limitations and other mobility impairments. Use of NMES has the potential to improve metabolic health analogous to voluntary exercise. Purpose: To determine the acute effect of 30 mins of NMES on energy metabolism and fasting blood glucose level. Methods: Fifteen participants without diabetes participated in the study (Males: 6; Females: 9; Age: 33.80 ± 12.99 years; BMI: 32.59 ± 9.17 kg/m2). Each participant underwent 30 mins of cyclical NMES on the quadricep muscles of both legs while lying supine on a bed. NMES was applied at a frequency of 50Hz with a pulse width of 300μs up to maximum tolerable intensity. Blood glucose and lactate levels were determined at baseline and at 5 mins intervals during the stimulation. Energy expenditure and substrate utilization were measured at baseline and monitored continuously during the NMES via indirect calorimetry. The experimental procedure was performed in a fasting condition and was directly preceded by a day of dietary control. Results: A decreasing blood glucose effect of NMES was observed between baseline glucose level (95.94 ± 7.81 mg/dL) and after 25 mins (92.85 ± 8.82 mg/dL) and 30 mins (91.79 ± 9.00 mg/dL) of NMES (p<0.05). Average energy expenditure rate during the 30min of NMES (19.37 ± 4.49 Kcal/kg/day) was relatively higher than that of the resting baseline rate (19.24 ± 3.57 Kcal/kg/day) (p<0.05). Blood lactate level and respiratory exchange ratio (substrate utilization) however, remained unaffected throughout the experimental procedure. Conclusion: Neuromuscular electrical stimulation is effective in decreasing blood glucose level and hence could serve as a beneficial intervention for blood glucose management. Supported by NIH Grant R01 DK132430 This is the full abstract presented at the American Physiology Summit 2023 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.
Placental-derived exosomal miR-125b disrupts maternal endothelial function in preeclampsia
Authors: Huang haiqin , Liu Xinlu , Li Qinghua , Su Hang , Meng Yuhan , Yang Weiwei 
Published: May 2023

Preeclampsia (PE) is an elusive life-threatening complication of pregnancy, and maternal endothelial dysfunction induced by components from the impaired placenta is a key hallmark of PE. Placenta-derived exosomes in maternal circulation has been reported with increased risk of PE, however, whether exosomes impaired endothelial cell function remains to be determined. We hypothesized that placental exosomes from preeclamptic patients disrupt endothelial function. We observed that placenta derived serum exosomes from preeclamtpic patients (PE-exo) significantly reduced VE-cadherin expression in primary cultured human umbilical vein endothelial cells (HUVECs), thus resulting in increased endothelial permeability. Realtime qPCR results indicated more miR‑125b in PE-exo. Moreover, we identified that VE-cadherin was a direct target of exosomal miR-125b in HUVECs. miR-125b could partly mediates the adverse effect of PE-exo on endothelial functions. Our findings suggest that miR-125b derived from placental exosomes is involved in the progression of PE and could be a promising therapeutic target for PE. This work was funded by grants from the Natural Science Foundation of Shandong Province (ZR2022MH195, ZR2019BH037), Graduate Student Research Grant from Weifang Medical University This is the full abstract presented at the American Physiology Summit 2023 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.
Allergen-stimulated secretion of DNA fragments by the airway epithelium enhances type 2 immune responses
Authors: Srisomboon Yotesawee , Iijima Koji , Colwell Mathia , Maniak Peter , Faulk Chris , Kita Hirohito , O'Grady Scott 
Published: May 2023

Exposure of human bronchial epithelial cells (hBECs) and mouse airways to allergens from the fungus Alternaria alternata triggers the release of alarmin signaling molecules including ATP, IL-33 and DNA fragments. The goal of this study was to determine the mechanisms that regulate release of genomic DNA fragments and how extracellular DNA (eDNA) contributes to type 2 immunity. Treatment of hBECs with Alternaria extract induces oxidative stress, which leads to ATP release and uptake of Ca2+ following activation of P2X receptors. DNA release was dependent on a sustained increase in intracellular [Ca2+], which stimulates cleavage of caspase 3 by the proprotein convertase enzyme furin, resulting in activation of caspase 3 and ultimately nuclear DNA fragmentation as shown in comet assays. Some of the fragmented DNA was released into the media under conditions where barrier function of the epithelium was maintained, and nuclear and plasma membranes remained intact. Alternaria-induced DNA release was detected within 30 minutes following exposure, reached its peak at 4 hours and ceased after 12 hours. Pretreatment of hBECs with a calpain inhibitor resulted in continued DNA release and loss of cell viability by 24 hours. This result suggested that calpain activity contributed to termination of Alternaria-evoked DNA release. In mice, intranasal administration of Alternaria extract produced release of DNA fragments into bronchoalveolar lavage (BAL) fluid over a similar time course as observed in hBECs. In caspase 3 deficient mice however, DNA release into BAL fluid was significantly reduced. Furthermore, Alternaria-induced type 2 immune responses were suppressed following pretreatment with a DNA scavenger. Conversely, intranasal administration of mouse genomic DNA with Alternaria amplified IL-5 and IL-13 secretion into BAL fluid while DNA alone had no effect. These findings indicate that DNA release from the airway epithelium is a regulated process involving noncanonical activation of caspase 3 to produce DNA fragmentation and calpain activity, which appears to be essential for the termination of DNA release. Moreover in airways, eDNA appears to function as a secondary alarmin that acts on immune cells to enhance type 2 immunity. This work was supported by grants from the NIH (AI128729 and AI169530) to HK and SMO. This is the full abstract presented at the American Physiology Summit 2023 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.