bluuebunny/crossref_metadata_2025_split huggingface dataset:
SPP1, a potential diagnostic marker that correlated with immune infiltration in right heart failure
Authors: Yang Xiaomei , Lu Kangping , Li Kai , Liu Zihua , Bai Yu , Yao Youxiu , Zhang Peng 
Published: May 2023

Background: Right ventricle failure (RVF) is a clinical syndrome with high mortality that is frequently secondary to cardiovascular and pulmonary vascular diseases. There is growing evidence that the outcome of RVF is closely related to the immune response. This study is to explore SPP1 as a potential diagnostic marker related to the infiltration of immune cells in RVF. Methods: The gene expression profile of GSE161473 was downloaded from Gene Expression Omnibus and analyzed by R. Protein-protein interaction (PPI) networks which were established with STRING. Gene Ontology and KEGG enrichment analysis were performed using R-package “Clusterprofiler.” Differentially expressed immune-related genes (DEIRG) were identified using ImmPort. The infiltration of immune cells in RVF was evaluated using CIBERSORT, and the correlation between key hub genes and immune cells was analyzed by R. Rats model of RVF which was established by monocrotaline (MCT) (60 mg/kg, IP). The immune status and differentially expressed immune-related genes (IRGs) in the right heart tissue of rats with RVF in PAH were verified by immunofluorescence, immunohistochemistry, Real-time PCR, and western blotting. In addition, the serum of right heart-failing patients was used to verify the possibility of SPP1 as a biomarker. Result: A total of 107 differentially expressed genes (DEGs) were screened, from which 20 DEIRGs were screened by ImmPort, PPI, and functional enrichment analysis. 4 Hub genes (ADM, FGF12, AREG and SPP1) were confirmed by RT-PCR. In addition, SPP1 was identified as the most potent biomarker. ImmuCellAI immune infiltration analysis showed that a higher proportion of monocytes, M2 macrophages, memory B cells, resting NK cells, and resting mast cells were elavated in the RVF group. Finally, SPP1 was positively correlated with monocytes and M2 macrophages and negatively correlated with memory B cells and CD8+ T cells. Conclusion: A variety of immune cells such as monocytes, macrophages, T cells, B cells, and mast cells are involved in the development of RVF. Dysregulated immune responses were found in the right cardiac tissue of patients with RVF. SPP1 was considered a key hub gene to discriminate between RVF and normal groups. Parts of IRGs, especially SPP1, may be used as biomarkers to assist in the diagnosis and evaluation of RVF. This work was supported by the Shandong Provincial Natural Science Foundation of China (ZR2022MH052), China Postdoctoral Science Foundation (No. 2021M691944) to Xiaomei Yang. 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.
Impact of Deep Reading in Case-Based Learning in Graduate Physiology Students
Authors: Brainard Robert , Britten Jack 
Published: May 2023

Introduction: In universities, a traditional lecture style has shown to be less effective in helping students learn compared to a more active approach to teaching and learning. Previous research has stated that passive learning triggers a shift to a more superficial style of learning that is associated with a lower level of cognitive skill. Active learning is defined as activities that students do to construct knowledge and understanding. An active learning concept known as deep reading has been suggested to improve academic performance. In recent studies, deep reading was utilized in graduate science courses and was shown to enhance reading and comprehension skills as well as increasing overall academic ability. Objective: In this study, the aim was to assess how deep reading impacted a student’s self-perception of their understanding of course material in a graduate-level physiology course. Methods: Over a six-week period, 23 graduate physiology students participated in weekly deep reading assignments that correlated with the material taught in class that week. At the end of each week, students filled out an evaluation form indicating how they felt their assigned reading impacted their understanding of the material taught in class. Results: Results indicated that almost 70% of the class agreed that deep reading helped in understanding the course material. Student feedback data showed frequent use of the words “understanding,” “enjoyed,” “relevant,” and “helped.” Students who spent between 0-2 hours per week deep reading gave positive feedback. Individuals who spent more than 2 hours per week indicated negative feedback and perceived that deep reading counteracted their understanding of course material. Conclusion: The data implies that student understanding of material was improved with 0-2 hours of deep reading per week. More than 2 hours of deep reading per week had a countereffect. Excess time spent reading could have caused students to lose sight of the important concepts from the articles and thereby eliciting a negative effect and more confusion. Some, 1-2hrs, seemed to be helpful, however, more had a detrimental effect on learning. Future studies should aim to have more consistency in the difficulty of reading materials between students. Addition of comprehensive reading questions could also be implemented to assess student understanding. Overall, we found in this study that deep reading, when used in moderation, was effective in helping students learn and see real-world application of concepts learned in class 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.
MicroRNA-206 improves alcohol-mediated decreased myoblast differentiation
Authors: Bergeaux Peter , Bourgeois Brianna , Molina Patricia , Simon Liz 
Published: May 2023

Background: With recent advances in antiretroviral therapy (ART), people living with HIV (PLWH) have a near-normal life expectancy but have higher risk for aging-related comorbidities, such as metabolic disorders and frailty earlier in life than the general population. At-risk alcohol use is twice as likely in PLWH compared to the general population and alcohol-related myopathy occurs in 40- 60% of people with alcohol use disorder. Previous studies demonstrated that in vivo chronic binge alcohol (CBA) administration in simian immunodeficiency virus (SIV)-infected male rhesus macaques decreased myoblast differentiation and downregulated microRNA-206 (miR-206) expression in skeletal muscle. We hypothesized that increasing miR-206 expression would increase differentiation in CBA-derived primary macaque myoblasts. Methods: Eight SIV-infected female rhesus macaques received either water (VEH) or CBA (13- 14 g/kg/week) for 14.5 months. Three months into either VEH or CBA administration, animals were vaginally infected with SIVmac251, and ART was started 2.5 months later. Animals were sacrificed after 9 months, and primary myoblasts isolated from vastus lateralis muscle 24 hours after the last dose of alcohol (blood alcohol=0 mM). Myoblasts at passage 4 (VEH & CBA) were proliferated for three days. Cells were then transfected with either miR-206 mimic or control (miR scramble). Four experimental groups were studied at day 5 of differentiation: VEH+scramble, CBA+scramble, VEH+miR-206, and CBA+miR-206. Expression of miR-206 was determined by qPCR. Myoblast differentiation was determined by myotube density, calculated as the average number of myotubes per frame, and fusion index calculated as the percentage of myonuclei that fused into myotubes. Results: In non-transfected CBA-derived cells, myotube density and miR-206 expression was lower compared to VEH-derived myotubes (p<0.001 and p<0.05, respectively). miR-206 transfection resulted in over 150-fold higher miR-206 expression compared to VEH-scramble (p<0.05) in CBA- and VEH-derived cells. miR-206 overexpression significantly increased myotube fusion index (p<0.05) compared to myoblasts transfected with miR scramble in CBA-derived cells. Conclusions: Data show significant improvement of alcohol-mediated decreased myoblast differentiation with miR-206 overexpression. These findings suggest that increasing muscle miR-206 can potentially be used as a therapeutic strategy to improve regenerative capacity in response to muscle injury or atrophy. (Supported by: T35AA021097, F30AA029358, P60AA009803, K01AA024494) 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.
Metabolism-insulin secretion coupling in pancreatic beta-cells: the protective role of urolithin B towards IAPP aggregation, insulin release and mitochondrial respiration
Authors: Monteiro Rodrigues Luis , Ferreira Sofia , Raimundo Ana , Pobre Vania , Garcez Marcia , da Silva Mafalda , Brito Jose , dos Santos Daniel , Saraiva Nuno , Homem Catarina , dos Santos Claudia , Echaniz Regina 
Published: May 2023

Intracellular aggregation and pancreatic deposition of Islet Amyloid Polypeptide (IAPP, or amylin) is an important trigger of β-cell dysfunction in type 2 diabetes and prevention of this process represents an attractive strategy to improve β-cell functionality. (Poly)phenols, particularly small molecule polyphenol metabolites (SMPMs) resulting from the metabolism by the colonic microbiota, have emerged as promising lead molecules.This study aimed to identify SMPMs inhibiting IAPP aggregation and to elucidate their activity towards the improvement of β-cell function. Docking analyzes revealed urolithin B (UroB) as the SMPM with the highest potential to interact with IAPP. In cell-free assays, UroB modulated the aggregation kinetics of IAPP fibril formation probably due to its accommodation in the hydrophobic pocket of IAPP monomer. The cytoprotective effects of UroB were then investigated in INS-1 832/3 pancreatic β-cells challenged with in vitro pre-formed IAPP aggregates. The pre-treatment of cells with 50 μM urolithin B for 12 h ameliorated IAPP-impaired cell viability and improved redox homeostasis and membrane integrity. Transcriptomic analysis pointed out Ca2+-signaling, and insulin secretion as top molecular pathways enriched in IAPP-exposed cells treated with UroB compared to the untreated control. Corroborating this, UroB protected against Ca2+ imbalance and mitochondrial dysregulation, resulting in improved glucose stimulated insulin secretion. Monitoring of oxygen consumption rate showed that UroB restored the mitochondrial respiration function in cells damaged by IAPP aggregates. Particularly, UroB re-established the energetic demand of the cells under baseline conditions, restored the ATP levels produced by the mitochondria, and rescued the spare respiratory capacity of cells subjected to IAPP insult. These effects translate into an increased capacity of cells to respond to energetic demands and, consequently, an improved cell fitness.Overall, our data revealed that UroB inhibits IAPP aggregation and modulates diverse cellular mechanisms assisting β-cells to deal with IAPP damage. This study discloses a novel set of molecules, the SMPMs, with the potential to prevent IAPP proteotoxicity and to promote metabolic homeostasis. This research is funded by Fundação Ciência Tecnologia (FCT) by grant UIDB/04567/2020. R. Menezes is supported by the Science Employment Stimulus program from FCT. 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.
The worsening of cardiac function by the repeated micro-embolization attenuates the very short-term blood pressure lability index in dogs
Authors: Yoshida Yuki , Kakuuchi Midori , Uemura Kazunori , Yokota Shohei , Matsushita Hiroki , Kawada Toru , Saku Keita 
Published: May 2023

Background: Recently, we developed a novel method for the assessment of very short-term blood pressure lability (BLI). BLI is calculated from the integrated area of blood pressure (BP) power spectral density from 0.01 Hz to 0.1 Hz. Given that low cardiac function suppresses blood pressure (BP) variation, we investigated how the worsening of cardiac function can be reflected in BLI by using a dog model of heart failure with reduced ejection fraction (HFrEF). Methods: In 6 dogs, chronic heart failure was induced through the use of multiple sequential microembolization via bolus injection of polyester microspheres (90μm) into the left descending or circumflex coronary arteries. We repeated coronary microembolization every two weeks and checked the arterial pressure, left ventricular pressure, and echocardiogram under general anesthesia in every session. BLI was calculated from the continuous BP recording by the catheter placed at ascending aorta before micro-embolization. We examined the changes of cardiac function and BLI, and compared them among the sessions of microembolization. Results: In every dog, the repeated microembolization significantly reduced left ventricular ejection fraction　(Baseline: 66±4 vs. HF: 38±6, %, P<0.01) and increased left ventricular end diastolic volume (Baseline: 23±4 vs. HF: 36±4, ml, P<0.01), indicating the worsening of cardiac function and remodeling. Although the mean BP did not change significantly, the BLI were significantly lower in heart failure condition (6±2 times microembolization) compared to baseline (Baseline: 0.7±0.2 vs. HF: 0.4±0.1, mmHg, P<0.05). Conclusions: Our findings demonstrate that the BLI in a HFrEF model dog was lower than that in baseline condition with normal hemodynamics. The BLI showed the potential for the assessment of the cardiac function and hemodynamic severity in HFrEF. 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.
Shear stress facilitates Akt activation in human pulmonary microvascular endothelial cells
Authors: Yan Simin , Philip Nicolas , Quintara Celia , Damarla Mahendra , Suresh Karthik , Shimoda Larissa , Kolb Todd 
Published: May 2023

Introduction: Pulmonary arterial obstruction due to acute thromboembolism causes local reduction or cessation of blood flow. Under normal conditions, pulmonary blood flow exerts shear stress on endothelial cells, known to play an important role in maintaining vascular homeostasis. We hypothesized that pulmonary microvascular endothelial cells exposed to abrupt reductions in shear stress would demonstrate attenuated phosphatidylinositol 3-kinase (PI3K)-dependent signaling and phosphorylation of downstream effectors Akt and endothelial nitric oxide synthase (eNOS). Methods: We tested our hypothesis in primary cultures of human lung microvascular endothelial cells (hLMVECs). We cultured early passage (p≤8) hLMVECs from 5 unique donor lots in standard 6-well culture plates and exposed cells to shear stress using an orbital shaker. Using a fixed depth (volume) and viscosity of tissue culture media, we adjusted the magnitude of shear stress exerted on hLMVECs by changing the angular velocity of orbital rotation. We acclimatized hLMVECs to physiologically-relevant shear stress (~12 dyn/cm2) for 24 hours, then exposed cells to low shear stress (~3 dyn/cm2) or no shear stress (0 dyn/cm2) for 30 minutes. Control cells were maintained at 12 dyn/cm2 of shear stress. In some experiments, PI3K activity was inhibited throughout the acclimatization and shear stress manipulation period by including LY294002 (10 μM) or vehicle (DMSO, 0.1% v/v) in culture media. We prepared whole cell lysates and used western blot to evaluate the expression and phosphorylation of Akt (ser473) and eNOS (ser1177). Results: We found that phosphorylation of Akt, but not Akt expression, decreased significantly (p<0.05) when shear stress was acutely reduced (~3 dyn/cm2) or removed (0 dyn/cm2). Inhibition of PI3K activity with LY294002 further diminished shear-mediated changes in Akt phosphorylation in all 3 groups. Conversely, eNOS phosphorylation was not modified by acute reductions in shear stress, but eNOS expression was markedly attenuated by PI3K inhibition under all conditions. Conclusions: Our results indicate that phosphorylation of Akt, but not its downstream target eNOS, is rapidly attenuated by abrupt reductions in shear stress in hLMVECs. However, shear stress appears to regulate eNOS expression in a PI3K-dependent manner. Taken together, these findings suggest that acute disruption of flow, as seen in pulmonary embolism, may disrupt human lung microvascular endothelial cell homeostasis and nitric oxide bioavailability via multiple PI3K-dependent signaling pathways. This work is supported by HL126514 and HL159906. 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.
Effect of Acute Diathermy on Leg Blood Flow and Vascular Function
Authors: Richard Kimberly , Wallace Taysom , Gifford Jayson , Nelson W 
Published: May 2023

Endothelial dysfunction is a common predecessor of many cardiovascular diseases. Heat therapy has been shown to improve cardiovascular health by stimulating changes within the endothelium. The purpose of this study was to examine the effect of acute diathermy, a heating modality, on leg blood flow and endothelial function. We hypothesized that diathermy treatment would increase leg blood flow compared to baseline, as well as increase endothelial function, as measured by peak increase in blood flow during passive leg movement. Nine healthy, young subjects (4 males, 5 females; mean (± SD) age = 23 ± 3.2 years, height = 174.8 ± 9.6 cm, mass = 74 ± 11.5 kg, body mass index = 24.1 ± 1.2) with no history of cardiovascular disease volunteered for this study. Subjects underwent 100 minutes of diathermy treatment on the vastus lateralis of a single, randomly assigned leg. Blood flow was measured at the common femoral artery using a Doppler ultrasound before, immediately after, and 30 minutes after heating. Passive leg movement was performed on the subjects before heating, and 30 minutes post-heating and peak blood flow was measured using Doppler ultrasound. Blood flow was found to significantly increase 20.4% from baseline to immediately post-heating (baseline, 355.3 ± 145.7 mL·min-1, immediately post, 428 ± 111.1 mL·min-1, p=0.045), and returned to baseline 30 minutes post-heating (30 min post, 361 ± 101.3 mL·min-1, p=0.853). Additionally, peak leg blood flow during passive leg movement significantly increased by 19.8% from baseline to 30 minutes post-heating (baseline, 1046.4 ± 379 mL·min-1, 30 min post, 1253.4 ± 430.2 mL·min-1, p=0.029). In conclusion, both leg blood flow and endothelial function, assessed by peak leg blood flow, significantly increased from baseline following 100 minutes of diathermy treatment. These data provide evidence for the benefits of acute diathermy treatment in improving leg vascular function via enhancements to endothelial function. 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.
Developing a mathematical model for early detection of viral hepatitis induced liver dysfunction
Authors: Agrawal Deepak Kumar 
Published: May 2023

Acute liver failure (ALF) is characterized by a sudden loss of hepatic function within a few weeks without pre-existing cirrhosis or prior history of liver disease. ALF can be difficult to identify using non-invasive methods such as coagulation abnormality and encephalopathy alone as alternative causes may confound the ALF diagnostic. This often results in delayed treatment at the onset of the disease, and a liver transplant might be the only option for ALF patients with a limited success rate. Due to these variables, ALF treatment is highly subjective to the clinicians' expertise, with a very high morbidity and mortality rate. Therefore, a prognostic model can help identify patients who can be managed with medical treatments and those who need liver transplants, along with an optimum intervention time window. Currently, only statistical models are available to identify ALF, such as King's College Hospital criteria, Clichy criteria, and End-Stage Liver Disease score. While these models provide much-needed critical support to clinicians, these models have limited specificity and sensitivity toward the cause of ALF and liver disease progression. For example, among all the common causes, the viral hepatitis-induced liver disease remains a major cause of ALF in developing countries such as in India and Bangladesh. Therefore, a dynamic patient-specific model is needed to improve patient care by correlating liver dysfunction with various healthcare variables and interventions. In this work, a new physiological linked data-driven model is formulated that can track the progression of liver disease and failure due to viral hepatitis. The approach relies on integrating the dynamics of healthy hepatocytes with immune system response, which is a vital component in tracking the time-sensitive infectious disease progression. The model uses the patient-specific measured values of alanine transaminase and aspartate transaminase enzymes and the clinically calculated international normalized ratio value to estimate the sensitive model parameter. This patient-specific model is then used to determine the disease progression by predicting the number of damaged hepatocytes and correlating it with the indication criteria for liver transplantation. The model can reproduce the essential dynamics seen in the ALF patient data and can be adapted to incorporate the effect of different therapeutic interventions. Thus, providing a vital bridge between understanding and treating viral hepatitis-induced liver dysfunction. No conflicts of interest, financial or otherwise, are declared by the author. 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.