Physiology最新文献

{"title":"Physiology in Perspective.","authors":"Christopher England","doi":"10.1152/physiol.00014.2023","DOIUrl":"https://doi.org/10.1152/physiol.00014.2023","url":null,"abstract":"<p><p>This issue of <i>Physiology</i> features four excellent review articles that highlight current research and discuss untapped areas for future work across a range of topics in physiology. First, we explore the impact that the loss of the Y chromosome in white blood cells has on men's health. Next, we discuss the pathophysiological roles of the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) in chronic inflammation. Third, we discuss how certain animals remain hydrated in seawater. Finally, we present on the systemic reprogramming of endothelial cell signaling in metastasis and cachexia.</p>","PeriodicalId":49694,"journal":{"name":"Physiology","volume":"38 4","pages":"160"},"PeriodicalIF":8.4,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9691348","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":"Staying Hydrated in Seawater.","authors":"Martin Grosell,&nbsp;Amanda M Oehlert","doi":"10.1152/physiol.00005.2023","DOIUrl":"https://doi.org/10.1152/physiol.00005.2023","url":null,"abstract":"<p><p>Reduction of intestinal lumen osmotic pressure by the formation of Ca(Mg)CO₃, \"ichthyocarbonate,\" is essential for osmoregulation by the only vertebrate group, ray-finned fishes, widely capable of hydrating by ingesting seawater. Ichthyocarbonate formation and excretion are under elaborate physiological control and play an important, yet still poorly defined, role in the oceanic carbon cycle.</p>","PeriodicalId":49694,"journal":{"name":"Physiology","volume":"38 4","pages":"0"},"PeriodicalIF":8.4,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9956032","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":"Pathophysiological Roles of the cGAS-STING Inflammatory Pathway.","authors":"Hiroshi Maekawa,&nbsp;Margaret Elizabeth Fain,&nbsp;Koichiro Wasano","doi":"10.1152/physiol.00031.2022","DOIUrl":"https://doi.org/10.1152/physiol.00031.2022","url":null,"abstract":"<p><p>The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) inflammatory pathway is a component of the innate immune system that recognizes cytosolic nucleic acids. The pathway has been implicated in several processes including aging, autoinflammatory conditions, cancer, and metabolic diseases. The cGAS-STING pathway represents a promising therapeutic target in a variety of chronic inflammatory diseases.</p>","PeriodicalId":49694,"journal":{"name":"Physiology","volume":"38 4","pages":"0"},"PeriodicalIF":8.4,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9604216","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":"Corrigendum for Lee CE, volume 36, 2021, p. 335–349","authors":"","doi":"10.1152/physiol.0009.2021_COR","DOIUrl":"https://doi.org/10.1152/physiol.0009.2021_COR","url":null,"abstract":"","PeriodicalId":49694,"journal":{"name":"Physiology","volume":"38 4","pages":"0"},"PeriodicalIF":8.4,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9569504","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":"Mosaic Loss of Y Chromosome in White Blood Cells: Its Impact on Men's Health.","authors":"Soichi Sano, Mark C Thel, Kenneth Walsh","doi":"10.1152/physiol.00008.2023","DOIUrl":"10.1152/physiol.00008.2023","url":null,"abstract":"<p><p>We present a brief introduction of loss of Y chromosome (LOY) in blood and describe the known risk factors for this condition. We then overview the associations between LOY and age-related disease traits. Finally, we discuss murine models and the potential mechanisms by which LOY contributes to disease.</p>","PeriodicalId":49694,"journal":{"name":"Physiology","volume":"38 4","pages":"0"},"PeriodicalIF":5.3,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10281780/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9705887","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systemic Reprogramming of Endothelial Cell Signaling in Metastasis and Cachexia.","authors":"Stephanie F Preuss,&nbsp;Denise Grieshober,&nbsp;Hellmut G Augustin","doi":"10.1152/physiol.00001.2023","DOIUrl":"https://doi.org/10.1152/physiol.00001.2023","url":null,"abstract":"<p><p>Proliferating cancer cells secrete a multitude of factors impacting metabolism, interorgan communication, and tumor progression. The distribution of tumor-derived factors to distant organs occurs via the circulation, which provides an extensive reactive surface lined by endothelial cells. Primary tumor-derived proteins impact cancer progression by modulating endothelial cell activation at the (pre-)metastatic niche, which affects tumor cell dissemination as well as the outgrowth of seeded metastatic cells into overt tumors. In addition, new insight indicates that endothelial cell signaling contributes to metabolic symptoms of cancer, including cancer-associated cachexia, opening a new field of vascular metabolism research. This review addresses how tumor-derived factors systemically affect endothelial cell signaling and activation and impact distant organs as well as tumor progression.</p>","PeriodicalId":49694,"journal":{"name":"Physiology","volume":"38 4","pages":"0"},"PeriodicalIF":8.4,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10281790/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9710402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteinuria observed post-uninephrectomy stems from partial suppression of protein endocytosis along the proximal tubule","authors":"A. Edwards, D. Ralph, Hillmin Lei, Taylor S. Priver, A. McDonough","doi":"10.1152/physiol.2023.38.s1.5728886","DOIUrl":"https://doi.org/10.1152/physiol.2023.38.s1.5728886","url":null,"abstract":"Living kidney donors are at higher risk of developing proteinuria, yet few studies have addressed the etiology. To investigate whether post-uninephrectomy (UNX) proteinuria was due to increased filtration and/or reduced endocytosis/reabsorption along the proximal tubule (PT), we compared renal function, morphology, and PT endocytic machinery in male Sprague Dawley rats before and after UNX.At 12 wk post-UNX, the weight of the remnant kidney rose by 50%, PT diameters by 30%, and single nephron GFR by 50% (based on 26% fall in creatinine clearance and 50% decrease in the number of nephrons). Urinary albumin excretion increased 10-fold post-UNX. Since the filtered load of proteins decreases in parallel with GFR post-UNX, increased albumin excretion likely reflects decreased endocytosis along the PT, a notion supported by a 50% reduction in abundance of albumin and plasminogen in renal cortex homogenates from remnant versus explant kidneys. We tested the hypothesis that the protein endocytic machinery was reduced following UNX. Immunoblot assays of renal cortex revealed decreased abundance of megalin and Dab2, two key mediators of protein endocytosis along the PT, and no change in cubilin abundance. Immunohistochemistry confirmed a 50% fall in megalin along the PT apical membrane.Mathematical modeling predicted that albumin uptake per nephron increases post-UNX, owing to higher single nephron GFR and PT hypertrophy, but is attenuated by the decrease in megalin abundance; moreover, modeling predicts that if the endocytic machinery were not partly suppressed, overall albumin excretion would remain at pre-UNX levels.In addition to albumin, urinary plasminogen and angiotensinogen were similarly increased post-UNX, while uromodulin (synthesized and secreted distally) was decreased post-UNX. Urinary biomarkers of renal injury, RBP4 and KIM-1, were increased post-UNX likely reflecting the impact of the increased endocytosis of albumin which can carry bound toxic lipids into the PT.Taken together, our findings suggest that the blunting of albumin endocytosis post-UNX, apparent as increased albuminuria, may serve to protect PT cells from albumin-induced cytotoxicity. DK083785; Keck School of Medicine Dean’s Pilot Funding 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":"45 1","pages":""},"PeriodicalIF":8.4,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73258203","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":"Alpha-glucosidase inhibitor mitigates bone loss in type-1 diabetes","authors":"S. Juin, S. Pushpakumar, U. Sen","doi":"10.1152/physiol.2023.38.s1.5734415","DOIUrl":"https://doi.org/10.1152/physiol.2023.38.s1.5734415","url":null,"abstract":"Diabetic nephropathy is a hallmark of diabetes mellitus (DM) and is characterized by kidney dysfunction. The kidney plays an important role in bone health by preserving the equilibrium of minerals viz., calcium and phosphate in the blood and 1,25-Dihydoxyvitamin D3 (Calcitriol) production. Previous studies have suggested that renal dysfunction is associated with dysregulated mineral reabsorption due to mineral-hormone imbalance, leading to bone loss and increased fracture risk in DM. Alpha-glucosidase inhibitor (AGI) is known to decelerate carbohydrate catabolism and delay glucose production to improve overall diabetic health. Nimbidiol is an AGI derived from the medicinal plant, Azadirachta indica and is considered a potential anti-diabetic natural compound. The purpose of our present study was to investigate whether AGI mitigates the imbalance of mineral homeostasis and eventual bone loss in type-1 diabetes. Twelve - fourteen weeks old wild-type, C57BL/6J (WT) and type-1 diabetic, C57BL6/‐ Ins2Akita /J (Akita) mice were either treated with saline or AGI (0.40 mg kg-1 d-1) by subcutaneous implantation of micro-osmotic pump for eight weeks. Diabetic Akita mice showed a distinct downregulation of sodium-phosphate co-transporter, Npt2a expression in the renal tubules compared to the WT mice. In addition, Akita mice exhibited a significant increase in alkaline phosphatase activity and decrease in Calcitriol and bone minerals such as calcium and phosphate levels in the blood. The changes were associated with a significant bone loss as evidenced by the increased thinning and porosity of cortical and trabecular bone and reduction of osteoblasts and osteocytes in diabetic femur. AGI treatment mitigated the pathological changes in Akita mice. Taken together, our results suggest that AGI preserves mineral homeostasis and thereby protects from bone loss in type-1 diabetes. DK116591 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":"8 1","pages":""},"PeriodicalIF":8.4,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73303902","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":"Role of scleraxis in angiotensin II-induced cardiac fibrosis","authors":"Sikta Chattopadhyaya, R. Nagalingam, D. Ledingham, M. Czubryt","doi":"10.1152/physiol.2023.38.s1.5725178","DOIUrl":"https://doi.org/10.1152/physiol.2023.38.s1.5725178","url":null,"abstract":"Cardiac fibrosis involves the activation and conversion of fibroblasts to myofibroblasts in response to pathophysiological stresses, resulting in structural and functional remodeling of the heart leading to heart failure and death. Although it affects millions of people worldwide, currently no medications are available against cardiac fibrosis. Similar to the pro-fibrotic growth factor TGF-β, angiotensin II (AngII) contributes to cardiac fibrosis, however AngII inhibitors are not used against fibrosis despite growing evidence of efficacy. AngII induces the nuclear translocation of Myocardin Related Transcription Factor-A (MRTF-A) which acts with Serum Response Factor (SRF) to play a major role in the conversion of fibroblasts to myofibroblasts, similar to the transcription factor scleraxis. Scleraxis has been shown by our lab to induce fibrosis by transactivating various pro-fibrotic gene promoters. Here we investigated whether AngII works through an MRTF-A/SRF/scleraxis pathway to induce cardiac fibrosis. AngII delivery (1mg/kg/day for 28 days) through osmotic mini-pumps in C57Bl/6 mice significantly increased blood pressure (systolic, diastolic, and mean) and cardiac hypertrophy compared to saline control group. In the AngII group, cardiac fibrosis was observed with enhanced mRNA expression of pro-fibrotic genes, Col1a1, Col3a1, periostin, and EDA-fibronectin. Interestingly there was a significant increase in scleraxis as well, suggesting its involvement in AngII-mediated fibrosis. Our in vitro studies of rat cardiac fibroblasts treated with AngII showed a significant increase in scleraxis mRNA and protein expression, and scleraxis knockdown significantly attenuated AngII-induced collagen expression, confirming a requirement for scleraxis in the AngII-mediated fibrosis pathway. NIH3T3 cells transfected with MRTF-A and SRF together showed a high level of induction of scleraxis expression. Luciferase assays in both COS7 and NIH3T3 cells showed that MRTF-A and SRF act together to regulate scleraxis expression by binding to and transactivating the scleraxis promoter, indicating that AngII activates a MRTF-A/SRF/scleraxis pathway for inducing cardiac fibrosis, therefore targeting scleraxis may be an effective anti-fibrotic strategy. Canadian Institutes of Health Research Project Grant 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":"100 1","pages":""},"PeriodicalIF":8.4,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73313088","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":"Maximal aerobic capacity is not correlated with microvascular nitric oxide contribution to endothelium- or beta-2-adrenergic receptor-dependent vasodilation in female adults","authors":"Gabrielle A. Dillon, J. Barnes, J. Limberg, S. Ranadive, Sarah Baker, T. Curry, M. Joyner, R. Harvey","doi":"10.1152/physiol.2023.38.s1.5732410","DOIUrl":"https://doi.org/10.1152/physiol.2023.38.s1.5732410","url":null,"abstract":"Background: The menopausal transition is characterized by impairments in microvascular endothelium- and β2-adrenergic receptor (β2AR)-dependent vasodilation, both mediated in part by nitric oxide. Greater aerobic capacity is associated with preserved endothelium-dependent vasodilation in middle-aged and older males, but not estrogen-deficient postmenopausal females. However, the association between aerobic capacity and the nitric oxide contribution to endothelium-dependent vasodilation has not been described in pre- or postmenopausal females. Further, the association between aerobic capacity and β2AR-dependent vasodilation in pre- and postmenopausal females remains elusive. Thus, this study tested the hypothesis that maximal aerobic capacity (V̇O2max) and endothelium- and β2AR-dependent vasodilation (and their respective nitric oxide contributions) would be positively correlated in premenopausal, but not estrogen-deficient postmenopausal females. Methods: Ten premenopausal (PRE, 27±3 yrs) and ten postmenopausal (PM, 59±4 yrs) females participated. V̇O2max was determined by a graded exercise test on a cycle ergometer. Brachial arterial catheters were placed for continuous blood pressure measurement and pharmacologic infusions. Forearm blood flow (FBF) was measured (venous occlusion plethysmography) at baseline (saline infusion) and during infusion of an endothelium-dependent vasodilator (acetylcholine: 1, 2, 4, 8 μg/100mL tissue/min) and β2AR agonist (terbutaline: 0.1, 0.5, 1, 2 μg/100mL tissue/min), both with and without a nitric oxide synthase inhibitor co-infusion (L-NG-monomethylarginine [L-NMMA]: 1 mg/min). Forearm vascular conductance (FVC) was calculated as FBF/mean blood pressure×100. Vasodilation was calculated as the area under the FVC dose response curve (AUC). The nitric oxide contributions were calculated as the difference between the AUC of acetylcholine or terbutaline alone and the AUC of the co-infusion with L-NMMA. Statistical analyses included independent t-tests and linear regression analysis. Results: V̇O2max was not different between groups (PRE: 35.4±8.3 vs. PM: 29.1±7.9 ml/kg/min, p=0.15). Endothelial and β2AR vasodilation were greater in pre- compared to postmenopausal females (endothelial: PRE 45±15 vs. PM 17±13 FVC AUC, p&lt;0.01; β2AR: PRE 35±12 vs. PM 18±11 FVC AUC, p&lt;0.01). V̇O2max was not correlated with endothelium-dependent vasodilation or the nitric oxide contribution of endothelium-dependent vasodilation in pre- or postmenopausal females (r=-0.48-0.06, p&gt;0.05 for all). V̇O2max was not correlated with β2AR-dependent vasodilation or the nitric oxide contribution of β2AR-mediated vasodilation in pre- or postmenopausal females (r=-0.27-0.26, p&gt;0.05 for all). Conclusion: In contrast to what has been previously observed in males, maximal aerobic capacity was not correlated with endothelium- or β2AR-dependent microvascular vasodilation ortheir respective nitric oxide contributions in pre- or postmenopausal females. AHA 14PR","PeriodicalId":49694,"journal":{"name":"Physiology","volume":"118 1","pages":""},"PeriodicalIF":8.4,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73512669","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}