Physiology最新文献

{"title":"Metabolism-insulin secretion coupling in pancreatic beta-cells: the protective role of urolithin B towards IAPP aggregation, insulin release and mitochondrial respiration","authors":"Luis Monteiro Rodrigues, Sofia Ferreira, A. Raimundo, V. Pobre, M. Garcez, Mafalda da Silva, Jose Brito, Daniel J. V. A. dos Santos, N. Saraiva, Catarina C. F. Homem, Claudia dos Santos, Regina Echaniz","doi":"10.1152/physiol.2023.38.s1.5790088","DOIUrl":"https://doi.org/10.1152/physiol.2023.38.s1.5790088","url":null,"abstract":"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.","PeriodicalId":49694,"journal":{"name":"Physiology","volume":"342 3","pages":""},"PeriodicalIF":8.4,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72388492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Addressing underrepresentation in physiology research through internship opportunities","authors":"Vincent Barnett, Steven Wu, Joseph Metzger, L. Anderson","doi":"10.1152/physiol.2023.38.s1.5735290","DOIUrl":"https://doi.org/10.1152/physiol.2023.38.s1.5735290","url":null,"abstract":"A challenge in the undergraduate physiology landscape is that some students who are underrepresented in the biomedical sciences are not aware of or are unable to take advantage of laboratory research opportunities. This is unfortunate because lab research can provide students with unique skill sets that are beneficial for future success, whether the students remain in research or move on to other careers. These skills include opportunities for critical thinking, improvement of oral and written communication skills, development of teamwork and leadership skills, learning about ethics in biomedical decision making and enhancement of digital literacy among others. As a program that sponsors an undergraduate Human Physiology major that has been successful in attracting underrepresented students (>40% students of color and >60% female) for a major Land-grant university, we challenged ourselves to consider how we might help our students make the most of their physiological interests and potentially improve the demographics of representation in our discipline. Starting in the summer of 2020, a group of faculty began a series of meetings to define an undergraduate program that would attract underrepresented students to lab-based internships, minimize the need for outside work by providing stipends and nurture their academic progress through informal student-faculty interactions. Though delayed by the Covid-19 pandemic, this framework has been used to initiate two new outreach programs. In the summer of 2021, we used this framework to initiate an American Heart Association sponsored research internship opportunity for 3rd and 4th year students. This program which we have named UPRIME is the focus of another abstract at this meeting. The INPUT (INtegrative biology and Physiology Undergraduate Training) program was started in fall of 2022. The program is internally supported and targets 1st and 2nd year undergraduates who represent populations that have been underrepresented in biomedical sciences. These students will be provided laboratory research experiences coupled with opportunities for educational support. A stipend of $3000 per student per semester is offered with the prospect of renewal dependent on a post-semester review. A cohort of six students were selected from a campus wide solicitation for applications into the inaugural INPUT class. These students will begin their projects in January 2023. We look forward to contributing to the scientific growth and development of these students. Perceptions of lab-based research and academic progress will be tracked along with career aspirations as the program progresses. Department of Integrative Biology and Physiology, University of Minnesota Medical School 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 ","PeriodicalId":49694,"journal":{"name":"Physiology","volume":"9 4","pages":""},"PeriodicalIF":8.4,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72493048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sympathetic transduction to blood pressure at rest is maintained in heart failure with preserved ejection fraction","authors":"S. Hissen, Ryosuke Takeda, Takuro Washio, John D Akins, C. Hearon, J. MacNamara, S. Sarma, B. Levine, P. Fadel, Qi Fu","doi":"10.1152/physiol.2023.38.s1.5731148","DOIUrl":"https://doi.org/10.1152/physiol.2023.38.s1.5731148","url":null,"abstract":"Introduction: The transduction of sympathetic vasoconstrictor drive to blood pressure (BP) at rest is blunted in patients with hypertension and heart failure with reduced ejection fraction. Whether this is the case in patients with heart failure with preserved ejection fraction (HFpEF), who have a high prevalence of hypertension, remains unknown. Furthermore, it is unclear whether the two established methods used to quantify sympathetic transduction at rest provide complementary information in patient populations. Therefore, the aim of this study was to comprehensively evaluate sympathetic transduction at rest in patients with HFpEF. We hypothesized that sympathetic transduction is blunted in patients with HFpEF compared to age-matched controls. Furthermore, we hypothesized that blunted sympathetic transduction in patients with HFpEF would be observed using both signal averaging and linear regression slope analyses techniques. Methods: BP, heart rate and muscle sympathetic nerve activity (MSNA, microneurography) were measured in 25 patients with HFpEF (70±8 (SD) years, 17 females) and 41 age-matched controls (70±6 years, 25 female; hypertension prevalence 66%) during 7-10 minutes of supine rest. In a subgroup, sympathetic transduction to diastolic BP in 13 HFpEF and 15 controls was evaluated using two analytical techniques: 1) signal averaging the beat-to-beat changes in diastolic BP following bursts of MSNA, with the peak change representing sympathetic transduction; and 2) the slope of the linear relationship between diastolic BP and MSNA burst area summed across a two cardiac cycle window at a fixed lag of 6-8 cardiac cycles preceding each diastolic BP. Results: Patients with HFpEF had similar resting BP (systolic 130±26 vs. 126±16 mmHg, P=0.89; diastolic 71±15 vs. 72±10 mmHg, P=0.64), greater heart rate (70±10 vs. 62±7 bpm, P<0.001) and a trend for greater MSNA burst frequency (39±15 vs. 32±12 bursts/min, P=0.06) but similar levels of MSNA burst incidence (55±20 vs. 51±20 bursts/100heartbeats, P=0.42) when compared with controls. In the subgroup, sympathetic transduction was comparable between HFpEF and controls when evaluated using both the signal averaging (Δ0.8±0.6 vs. Δ1±0.7 mmHg, P=0.45) and the linear regression slope (0.07±0.07 vs. 0.07±0.08 mmHg/%.s, P=0.33) methods. There was a moderate positive linear relationship between methods (r2=0.39, P<0.001). Conclusion: Contrary to our hypothesis, these preliminary findings suggest that sympathetic transduction to BP at rest is preserved in patients with HFpEF compared with age-matched hypertensive controls. Furthermore, the signal averaging and linear regression slope analyses approaches provide complementary information on resting sympathetic transduction in patients with HFpEF and age-matched controls. Whether sympathetic transduction to BP in response to physiological stressors is also altered in HFpEF remains to be determined. Supported by the National Institute of Health (P01HL137630 a","PeriodicalId":49694,"journal":{"name":"Physiology","volume":"57 1","pages":""},"PeriodicalIF":8.4,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72820822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"What really matters mobility of middle-aged and older adults: low muscle mass or obesity?","authors":"Chiao-Nan Chen, Kuo-Jen Hsu, Shu-Chen Chen, Kuei-Yu Chien","doi":"10.1152/physiol.2023.38.s1.5730639","DOIUrl":"https://doi.org/10.1152/physiol.2023.38.s1.5730639","url":null,"abstract":"Study objective: This study explored which body size–adjusted skeletal muscle indices (SMI) has a better correlation with mobility and cardiometabolic health. Additionally, the roles of low muscle mass and obesity in the mobility and cardiometabolic health of individuals were identified. We hypothesized that body mass index (BMI)-or body weight (Wt)-adjusted SMI had a better correlation with mobility in middle-aged and older adults with obesity than did body height (Ht)-adjusted SMI. Methods: 427 community-dwelling middle-aged and older adults (age: 66.0±9.0 years) underwent assessments of body composition (dual-energy X-ray absorptiometry and waist circumference [WC]), grip strength, and mobility (timed up-and-go test and chair stand test). WC was used as a surrogate for obesity. Chi-square test and one-way analysis of variance were used to compare grip strength, mobility, and cardiometabolic health among individuals with normal body composition (N), only low muscle mass (S), only obesity (O), and low muscle mass plus obesity (SO). Pearson’s correlation coefficient was used to examine the correlation between muscle strength/mobility and different body size–adjusted SMI. Regression models were used to examine the factors independently associated with muscle strength, mobility, and cardiometabolic health. The significance level was set at α<0.05. Results: The O group, but not the S group, had poorer mobility than the N group, regardless of the SMI used to define low muscle mass. The O and SO groups had a higher prevalence of cardiometabolic diseases. The relationship between muscle mass and mobility existed in individuals with obesity, but not in individuals without obesity. After adjusting for age, sex, and WC, ASM/BMI was the only SMI that was correlated with grip strength. Similarly, only ASM/BMI was positively correlated with performance on the timed up-and-go test in the population with obesity (p<0.05). When age and sex were controlled, WC, but not SMI (regardless of adjusting for Ht, Wt, or BMI), was associated with mobility and cardiometabolic health. Conclusion: BMI-adjusted SMI had a better correlation with mobility in middle-aged and older adults with obesity than did Ht- and Wt-adjusted SMI. Obesity plays a more independent role in mobility and cardiometabolic health than low muscle mass in middle-aged and older adults. This study was supported by the Ministry of Science and Technology, Taiwan 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.","PeriodicalId":49694,"journal":{"name":"Physiology","volume":"40 1","pages":""},"PeriodicalIF":8.4,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74556325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex differences in arterial stiffness and sympathetic activity in older CKD patients","authors":"M. Zanuzzi, Jinhee Jeong, Dana Dacosta, Jeanie Park","doi":"10.1152/physiol.2023.38.s1.5785895","DOIUrl":"https://doi.org/10.1152/physiol.2023.38.s1.5785895","url":null,"abstract":"Chronic kidney disease (CKD) is characterized by sympathetic nervous system overactivity that contributes to increased arterial stiffness and cardiovascular risk. While premenopausal females are relatively protected from cardiovascular disease in healthy individuals, older postmenopausal females without kidney disease have similar degrees of sympathetic overactivity, vascular stiffness and cardiovascular risk compared to older age-matched males in the general population. However, in the CKD population, cardiovascular mortality risk remains higher in older males compared to age-matched females and whether sex differences in neural and vascular function exist in older CKD patients is unknown. Therefore, we tested the hypothesis that compared to older females, older males with CKD have higher baseline sympathetic activity that is related to increased arterial stiffness. In 207 CKD patients (N=90 females, 62 ± 9 years; and N=117 males, 60 ± 9 years), we measured resting sympathetic nerve activity directed to muscle (MSNA) by microneurography at the peroneal nerve. At a separate visit, arterial stiffness was determined by carotid-to-femoral pulse wave velocity (PWV) using transcutaneous Doppler flow velocity (SphygmoCor®). Office blood pressure (BP) and 24-hour ambulatory BP monitoring (ABPM; Spacelabs) were performed using standard techniques. Resting MSNA was higher in males versus females with CKD (43 ± 10 vs 31 ± 14 bursts/min; p= 0.039). Both office and 24-hour ambulatory diastolic BP (79 ± 11 vs 67 ± 14 mmHg, p<0.001) and mean arterial pressure (96 ± 10 vs 88 ± 13 mmHg, p<0.001) were also higher in males versus females. PWV was not different between male and female groups (p= 0.157). There was no association between PWV and resting MSNA in males, while in females, there was an inverse relationship between PWV and MSNA burst frequency (r2=0.271; p=0.039) and burst incidence (r2=0.310; p=0.025). Older male CKD patients have higher resting MSNA, office and ambulatory BP compared to older females with CKD. In contrast, there were no differences in arterial stiffness measured as PWV between sexes. In males, increased MSNA was not associated with increased arterial stiffness, while MSNA was negatively correlated with PWV in females. Sex differences in neural and vascular function may impact cardiovascular outcomes in older patients with CKD. Supported by NIH grants R01HL135183, R33AT010457. 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.","PeriodicalId":49694,"journal":{"name":"Physiology","volume":"109 1","pages":""},"PeriodicalIF":8.4,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74570103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Periodontitis accelerates the development of arterial hypertension in spontaneously hypertensive rats (SHR)","authors":"T. Buzinari, J. Castania, S. Salvador, H. Salgado","doi":"10.1152/physiol.2023.38.s1.5729825","DOIUrl":"https://doi.org/10.1152/physiol.2023.38.s1.5729825","url":null,"abstract":"Objectives: Arterial hypertension and the inflammatory process are pathophysiologically associated. Of note, it is well understood that periodontitis is an inflammatory morbidity, epidemiologically related to cardiovascular mortality, particularly with the risk of developing arterial hypertension. Considering that in Spontaneously Hypertensive Rats (SHR) the elevation of arterial pressure starts from the 7th week of age, this study aimed to evaluate whether periodontitis accelerates the onset of arterial hypertension, for instance, in 5-week-old SHR. Methods: Induction of periodontitis was started in 3-week-old SHR and maintained for 2 weeks through the ligation of the left first molar with a silk suture, followed by the Porphyromonas gingivalis (strain W83) administration, p.o., 3 times a week. The femoral artery of 5-week-old SHR was cannulated, and 24 hours later, with the animals awakened, the systolic (SAP), diastolic (DAP), and mean (MAP) arterial pressures were recorded. Results: 5-week-old control SHR (SHAM) did not have installed arterial hypertension, while SHR with periodontitis (PER) exhibited a higher arterial pressure when compared to the SHAM group (SAP PER: 150±4 vs. SAP SHAM: 124±3 mmHg, n=8, p≤0.001; DAP PER: 103±5 vs. DAP SHAM: 85±5 mmHg, n=8, p≤0.05; MAP PER: 119±4 vs. MAP SHAM 98±4 mmHg n=8, p ≤0.01). Conclusion: The differences observed in the pressure values between the groups studied demonstrate that periodontitis accelerates the development of hypertension in SHR. Funding Sources: Fundação de Amparo à Pesquisa do Estados de São Paulo - FAPESP, Process 2021/08622-7 and 2020/06043-7. Conselho Nacional de Desenvolvimento Científico e Tecnológico - CNPq, Process 306994/2021-6 and 423999/2021-4. 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.","PeriodicalId":49694,"journal":{"name":"Physiology","volume":"53 1","pages":""},"PeriodicalIF":8.4,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74667329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic Potential of Extracellular Vesicles to Restore Alcohol-mediated Impairment of Myoblast Differentiation","authors":"L. Simon, B. Bourgeois, P. Molina","doi":"10.1152/physiol.2023.38.s1.5734763","DOIUrl":"https://doi.org/10.1152/physiol.2023.38.s1.5734763","url":null,"abstract":"At-risk alcohol use in people living with HIV (PLWH) and chronic binge alcohol (CBA) administration in simian immunodeficiency virus (SIV)-infected macaques are associated with dysfunctional skeletal muscle mass. Our studies have shown that decreased myomiR-206 expression in skeletal muscle and myoblasts isolated from CBA/SIV macaques contributes to decreased myoblast differentiation. miRs transported in extracellular vesicles (EVs) mediate numerous cellular responses through intercellular communication. This study tested the hypothesis that delivery of miR-206 in EVs would ameliorate CBA-mediated decreased myoblast differentiation. Eight female rhesus macaques received either (CBA, 2.5g/kg/day) or water (VEH) for 14.5 months. Three months following the initiation of CBA/VEH, animals were infected with SIVmac251 and initiated on antiretroviral therapy 2.5 months later. Myoblasts were isolated from the vastus lateralis muscle at study endpoint (blood alcohol concentration= 0 mM) from each animal and used for ex vivo experiments including measuring differentiation, transfecting with a miR-206 mimic, and isolating EVs from myotube culture supernatant via ultracentrifugation. Myoblast differentiation measured by fusion index was lower in CBA myotubes compared to VEH (p<0.05). CBA decreased myotube-derived EV miR-206 expression (p<0.01). Transfection of myoblasts isolated from the CBA group with a mir-206 mimic increased myotube fusion index (p<0.05). Moreover, delivery of exogenous miR-206 in plasma-derived EVs increased myotube expression of miR-206 by over 450-fold (p<0.001) and significantly improved myoblast differentiation as measured by fusion index and myotube density (p<0.05). These results provide evidence that delivering miR-206 through EVs can increase CBA-mediated SKM stem cell differentiation. We propose these findings support the possible use of autologous plasma EVs as therapeutical vehicles devoid of the known adverse effects of synthetic cargo nanocarriers. Supported by: NIH/NIAAA P60AA009803, F30AA029358, 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.","PeriodicalId":49694,"journal":{"name":"Physiology","volume":"94 1","pages":""},"PeriodicalIF":8.4,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77501012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Midbrain regions activated during copper-sulfate induced emesis in felines","authors":"Jacob T. Sampson, Xiaoying Dong, Carey D. Balaban, B. Yates","doi":"10.1152/physiol.2023.38.s1.5733894","DOIUrl":"https://doi.org/10.1152/physiol.2023.38.s1.5733894","url":null,"abstract":"The neural pathways that mediate emesis are still poorly defined. Most studies that considered emetic circuitry focused on the brainstem. The goal of this study was to map the distribution of Fos labeling in the feline midbrain following intragastric administration of copper sulfate (CuSO4). In 10 felines (6 male, 4 female), doses of CuSO4 ranging from 83 to 322 mg were administered through an intragastric catheter or gavage, and ~2 hours later animals were euthanized and perfused with paraformaldehyde. The brain was sectioned and processed for Fos labeling as in our prior study (Balaban et al., PLoS ONE 9(1): e86730, 2014). Three additional animals served as controls and did not receive intragastric CuSO4. Animals with emetic responses to CuSO4 exhibited extensive differential labeling in longitudinal columns within central/periaqueductal gray through the entire extent of the aqueduct of Sylvius. Labeling was present in the dorsolateral column of all animals, and differentially in the lateral column, ventrolateral column, ventromedial column, and the ventromedian area that caps the dorsal raphe nucleus. Fos labeling was also heavy in the dorsal tegmental area, superficial to the dorsal tegmental nucleus, locus coeruleus, pontine nuclei including the nucleus reticularis tegmenti pontis, and the dorsal raphe nucleus. Additional labeling was observed in the cuneiform nucleus, raphe centralis superior, and the Edinger-Westphal and anteromedial nuclei. This Fos labeling pattern is less circumscribed that reported for brainstem areas activated during CuSO4-induced vomiting in felines. Only diffuse labeling was noted in control animals. Ongoing studies are correlating physiologic responses to Fos labeling patterns induced by intragastric CuSO4. Midbrain neurons activated during emesis likely mediate affective responses during nausea, and likely also transmit visceral inputs elicited by CuSO4 to higher brain regions. NIH grant R01-DC018229 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.","PeriodicalId":49694,"journal":{"name":"Physiology","volume":"27 1","pages":""},"PeriodicalIF":8.4,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77559217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Teaching K-12 Students Using Jenga! The Impact of Health Behaviors on Community Health, Wellbeing, and Resilience","authors":"Kyle W. Wehmanen, Felix E Cottet-Puinel, Tyler C Hampton, Gwyn T Hamlin, Isaac J. Wedig, Steve L. Elmer","doi":"10.1152/physiol.2023.38.s1.5734574","DOIUrl":"https://doi.org/10.1152/physiol.2023.38.s1.5734574","url":null,"abstract":"As society continues to move forward from the COVID-19 pandemic, outreach with K-12 schools is critical for: 1) reestablishing connections with students and teachers and 2) generating interest in health-focused science, technology, engineering, and math (H-STEM) careers. The Department of Kinesiology and Integrative Physiology at Michigan Technological University leveraged the Michigan-Indiana Physiology Understanding Week and National Rural Health Day events to organize a health science-based outreach visit with local schools. Graduate students met with middle and high school students and presented a hands-on activity using the game Jenga to demonstrate the links between health behaviors, disease, and community health. For the activity, students worked together in small teams (e.g., 4-8 students) and were given two Jenga towers (Tower A and Tower B), each representing a community of individuals. The goal of the activity was to keep both towers standing strong. Teams were presented with 12 strips of paper labeled with either a ‘health behavior’ (e.g., physical activity, diet, body weight, smoking) or a ‘disease’ (e.g., heart disease, diabetes, influenza, COVID-19) and accompanying instructions on whether to add or remove blocks from each tower. When presented with a health behavior, students added blocks to Tower A for positive health behaviors (e.g., not smoking) and removed blocks from Tower B for negative health behaviors (e.g., smoking). When a disease was presented, students removed blocks from both towers, but fewer blocks were removed from Tower A compared to Tower B, demonstrating relatively lower diseases rates or severity in that community. As the activity progressed, Tower A retained more blocks than Tower B. For the grand finale, students observed that with the greater strength and stability of Tower A it was better equipped to withstand a natural disaster such as an earthquake that was simulated by students shaking the table that held both towers. At the end of the activity students were able to describe the connections between positive health behaviors and lower rates of disease, and how taken together, these impact overall community health, wellbeing, and resilience. This activity was delivered to 15 different science classes and 225 students ranging from 6-12th grade. The activity was well received by students and teachers and aligned with educational standards that focus on three-dimensional learning. The inclusion of graduate students as guest instructors improved their understanding of public health promotion and provided them with practice communicating health science to a lay audience. Importantly, connecting with K-12 schools to increase interest in H-STEM is an important step for helping to address the current healthcare workforce shortage. 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 ","PeriodicalId":49694,"journal":{"name":"Physiology","volume":"175 1","pages":""},"PeriodicalIF":8.4,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77631132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of Hydroxychloroquine on Natural Killer Cell Activity and Function","authors":"N. Elemam, I. Talaat, A. Maghazachi","doi":"10.1152/physiol.2023.38.s1.5732010","DOIUrl":"https://doi.org/10.1152/physiol.2023.38.s1.5732010","url":null,"abstract":"Background and Objectives: Inflammation is associated with different diseases ranging from autoimmunity, infections, and cancer. Immuno-modulatory drugs may have applications for treating various diseases, such as the case of anti-malarial hydroxychloroquine (HCQ). However, it remains unknown what is their direct mechanism of action on immune cells, which include natural killer (NK) cells. To investigate this issue, we examined the effects of HCQ on NK cell activity, including activating receptors’ expression, cytotoxic potential, and cytokine production. Materials and Methods: The human NK cell line NK92 was cultured in RPMI-1640 supplemented with 10% fetal bovine serum (FBS), 1% penicillin/streptomycin, and 200 IU/ml of IL-2. HCQ was added to the cells at different concentrations (1, 5, and 10 mM) and at different time points (24 and 48 hours). Post-treatment, NK92 cell viability was evaluated using the Cell Proliferation/XTT method. Protein expressions of NKG2D and CD107a were assessed using flow cytometry after 24 hours of treatment, while the cytotoxicity of NK cells was tested using the Calcein-AM method. The NK-sensitive K562 cells were cultured in RPMI-1640 supplemented with 10% FBS and 1% penicillin/streptomycin and were used as targets for NK92 cell-mediated killing. Also, IFN-g production by NK92 cells was measured by ELISA after 24 hours of treatment with HCQ. Statistical analysis was performed where p&lt;0.05 was considered statistically significant. Results: Upon treatment with different concentrations of HCQ for 24 hours, NK92 cells did not show any difference in their proliferation potential. However, after 48 hours, the viability of the cells significantly decreased in a dose-dependent manner, with the lowest viability noted at 10 mM of HCQ. Additionally, the expression of the activating receptor NKG2D was significantly reduced upon treatment with 5 and 10 mM of HCQ for 24 hours. Similarly, the degranulation marker CD107a significantly decreased upon HCQ treatment at all used concentrations. Similarly, the cytotoxicity of NK92 cells against K562 cells was reduced at both 5:1 and 10:1, effector to target (E: T) cell ratios, when 10 mM HCQ was used. On the other hand, IFN-g levels were significantly increased upon treatment with 1, 5, and 10 mM HCQ. Conclusions: This study highlights the effect of HCQ on activating receptors’ expression, cytotoxicity, and IFN-g production of NK cells. Our findings suggest that high doses of HCQ might impair the activation and cytolytic potential of NK cells but may increase their IFN-g production, which may recruit other cells into the inflammatory sites. Despite being an immunomodulatory drug, more studies are needed to further understand HCQ's effects on NK cells and perhaps other effector cells. 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. P","PeriodicalId":49694,"journal":{"name":"Physiology","volume":"1 1","pages":""},"PeriodicalIF":8.4,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77771996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}