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Search Results (1,278)

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Keywords = blood pressure responsiveness

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17 pages, 2050 KiB  
Article
Effects of Compression Pants with Different Pressure Levels on Anaerobic Performance and Post-Exercise Physiological Recovery: Randomized Crossover Trial
by Qinlong Li, Kaixuan Che, Wenlang Yu, Wenda Song and Yue Zhou
Sensors 2025, 25(15), 4875; https://doi.org/10.3390/s25154875 (registering DOI) - 7 Aug 2025
Abstract
Compression pants, as functional sportswear providing external pressure, are widely used to enhance athletic performance and accelerate recovery. However, systematic investigations into their effectiveness during anaerobic exercise and the impact of different pressure levels on performance and post-exercise recovery remain limited. This randomized [...] Read more.
Compression pants, as functional sportswear providing external pressure, are widely used to enhance athletic performance and accelerate recovery. However, systematic investigations into their effectiveness during anaerobic exercise and the impact of different pressure levels on performance and post-exercise recovery remain limited. This randomized crossover controlled trial recruited 20 healthy male university students to compare the effects of four garment conditions: non-compressive pants (NCP), moderate-pressure compression pants (MCP), high-pressure compression pants (HCP), and ultra-high-pressure compression pants (UHCP). Anaerobic performance was assessed through vertical jump, agility tests, and the Wingate anaerobic test, with indicators including time at peak power (TPP), peak power (PP), average power (AP), minimum power (MP), power drop (PD), and total energy produced (TEP). Post-exercise blood lactate concentrations and heart rate responses were also monitored. The results showed that both HCP and UHCP significantly improved vertical jump height (p < 0.01), while MCP outperformed all other conditions in agility performance (p < 0.05). In the Wingate test, MCP achieved a shorter TPP compared to NCP (p < 0.05), with significantly higher AP, lower PD, and greater TEP than all other groups (p < 0.05), whereas HCP showed an advantage only in PP over NCP (p < 0.05). Post-exercise, all compression pant groups recorded significantly higher peak blood lactate (Lamax) levels than NCP (p < 0.05), with MCP showing the fastest lactate clearance rate. Heart rate analysis revealed that HCP and UHCP induced higher maximum heart rates (HRmax) (p < 0.05), while MCP exhibited superior heart rate recovery at 3, 5, and 10 min post-exercise (p< 0.05). These findings suggest that compression pants with different pressure levels yield distinct effects on anaerobic performance and physiological recovery. Moderate-pressure compression pants demonstrated the most balanced and beneficial outcomes across multiple performance and recovery metrics, providing practical implications for the individualized design and application of compression garments in athletic training and rehabilitation. Full article
(This article belongs to the Section Biomedical Sensors)
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23 pages, 11168 KiB  
Article
Persistent Inflammation, Maladaptive Remodeling, and Fibrosis in the Kidney Following Long COVID-like MHV-1 Mouse Model
by Rajalakshmi Ramamoorthy, Anna Rosa Speciale, Emily M. West, Hussain Hussain, Nila Elumalai, Klaus Erich Schmitz Abe, Madesh Chinnathevar Ramesh, Pankaj B. Agrawal, Arumugam R. Jayakumar and Michael J. Paidas
Diseases 2025, 13(8), 246; https://doi.org/10.3390/diseases13080246 - 5 Aug 2025
Viewed by 57
Abstract
Background: Accumulating evidence indicates that SARS-CoV-2 infection results in long-term multiorgan complications, with the kidney being a primary target. This study aimed to characterize the long-term transcriptomic changes in the kidney following coronavirus infection using a murine model of MHV-1-induced SARS-like illness and [...] Read more.
Background: Accumulating evidence indicates that SARS-CoV-2 infection results in long-term multiorgan complications, with the kidney being a primary target. This study aimed to characterize the long-term transcriptomic changes in the kidney following coronavirus infection using a murine model of MHV-1-induced SARS-like illness and to evaluate the therapeutic efficacy of SPIKENET (SPK). Methods: A/J mice were infected with MHV-1. Renal tissues were collected and subjected to immunofluorescence analysis and Next Generation RNA Sequencing to identify differentially expressed genes associated with acute and chronic infection. Bioinformatic analyses, including PCA, volcano plots, and GO/KEGG pathway enrichment, were performed. A separate cohort received SPK treatment, and comparative transcriptomic profiling was conducted. Gene expression profile was further confirmed using real-time PCR. Results: Acute infection showed the upregulation of genes involved in inflammation and fibrosis. Long-term MHV-1 infection led to the sustained upregulation of genes involved in muscle regeneration, cytoskeletal remodeling, and fibrotic responses. Notably, both expression and variability of SLC22 and SLC22A8, key proximal tubule transporters, were reduced, suggesting a loss of segment-specific identity. Further, SLC12A1, a critical regulator of sodium reabsorption and blood pressure, was downregulated and is associated with the onset of polyuria and hydronephrosis. SLC transporters exhibited expression patterns consistent with tubular dysfunction and inflammation. These findings suggest aberrant activation of myogenic pathways and structural proteins in renal tissues, consistent with a pro-fibrotic phenotype. In contrast, SPK treatment reversed the expression of most genes, thereby restoring the gene profiles to those observed in control mice. Conclusions: MHV-1-induced long COVID is associated with persistent transcriptional reprogramming in the kidney, indicative of chronic inflammation, cytoskeletal dysregulation, and fibrogenesis. SPK demonstrates robust therapeutic potential by normalizing these molecular signatures and preventing long-term renal damage. These findings underscore the relevance of the MHV-1 model and support further investigation of SPK as a candidate therapy for COVID-19-associated renal sequelae. Full article
(This article belongs to the Special Issue COVID-19 and Global Chronic Disease 2025: New Challenges)
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15 pages, 787 KiB  
Review
Bradykinin Receptors in Metabolic Disorders: A Comprehensive Review
by Jéssica Branquinho, Raquel Leão Neves, Michael Bader and João Bosco Pesquero
Drugs Drug Candidates 2025, 4(3), 37; https://doi.org/10.3390/ddc4030037 - 5 Aug 2025
Viewed by 60
Abstract
The kallikrein–kinin system and its B1 and B2 receptors are key regulators in metabolic disorders such as obesity, diabetes, and insulin resistance. Obesity, a chronic and multifactorial condition often associated with comorbidities like type 2 diabetes and dyslipidemia, remains poorly understood at the [...] Read more.
The kallikrein–kinin system and its B1 and B2 receptors are key regulators in metabolic disorders such as obesity, diabetes, and insulin resistance. Obesity, a chronic and multifactorial condition often associated with comorbidities like type 2 diabetes and dyslipidemia, remains poorly understood at the metabolic level. The kinin B2 receptor (B2R) is involved in blood pressure regulation and glucose metabolism, promoting glucose uptake in skeletal muscle via bradykinin. Studies in B2R-KO mice demonstrate that the absence of this receptor predisposes animals to glucose intolerance under a high-fat diet and impairs adaptive thermogenesis, indicating a protective role for B2R in metabolic homeostasis and insulin sensitivity. In contrast, the kinin B1 receptor (B1R) is inducible under pathological conditions and is activated by kinin metabolites. Mouse models lacking B1R exhibit improved metabolic profiles, including protection against high-fat diet-induced obesity and insulin resistance, enhanced energy expenditure, and increased leptin sensitivity. B1R inactivation in adipocytes enhances insulin responsiveness and glucose tolerance, supporting its role in the development of insulin resistance. Moreover, B1R deficiency improves energy metabolism and thermogenic responses to adrenergic and cold stimuli, promoting the activation of brown adipose tissue and the browning of white adipose tissue. Collectively, these findings suggest that B1R and B2R represent promising therapeutic targets for the treatment of metabolic disorders. Full article
(This article belongs to the Special Issue Drugs of the Kallikrein-Kinin System)
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10 pages, 479 KiB  
Article
Evaluation of a Simplified Upper Arm Device for Vacuum-Assisted Collection of Capillary Blood Specimens
by Ulrich Y. Schaff, Bradley B. Collier, Gabriella Iacovetti, Mitchell Peevler, Jason Ragar, Nicolas Tokunaga, Whitney C. Brandon, Matthew R. Chappell, Russell P. Grant and Greg J. Sommer
Diagnostics 2025, 15(15), 1935; https://doi.org/10.3390/diagnostics15151935 - 31 Jul 2025
Viewed by 312
Abstract
Background/Objectives: Conventional blood collection can be challenging in a non-clinical or home-based setting. In response, vacuum-assisted lancing devices for capillary blood collection (typically from the upper arm) have gained popularity to broaden access to diagnostic testing. However, these devices are often costly relative [...] Read more.
Background/Objectives: Conventional blood collection can be challenging in a non-clinical or home-based setting. In response, vacuum-assisted lancing devices for capillary blood collection (typically from the upper arm) have gained popularity to broaden access to diagnostic testing. However, these devices are often costly relative to the reimbursement rate for common laboratory testing panels. This study describes the design and evaluation of Comfort Draw™, a simplified and economical vacuum-assisted capillary blood collection device. Methods: Comfort Draw™ was evaluated by 12 participants in a preliminary study and by 42 participants in a follow-up study. Metrics assessed included the following: vacuum pressure of the device, skin temperature generated by the Comfort Draw prep warmer, blood collection volume, and analytical accuracy (for 19 common serum-based analytes). Results: Acceptable blood volume (>400 µL) and serum volume (>100 µL) were collected by Comfort Draw in 85.5% and 95.1% of cases, respectively. Seventeen of the nineteen analytes examined were within CLIA acceptance limits compared to matched venous samples. Self-reported pain scores associated with Comfort Draw collection averaged 0.39 on a scale from 0 to 10. Conclusions: In this preliminary clinical study, Comfort Draw was found to be a valid and relatively painless method for collecting capillary blood specimens. The device’s simple design and lower cost could enable broader applications compared to more complex alternative capillary blood collection devices. Full article
(This article belongs to the Section Point-of-Care Diagnostics and Devices)
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42 pages, 28030 KiB  
Article
Can AI and Urban Design Optimization Mitigate Cardiovascular Risks Amid Rapid Urbanization? Unveiling the Impact of Environmental Stressors on Health Resilience
by Mehdi Makvandi, Zeinab Khodabakhshi, Yige Liu, Wenjing Li and Philip F. Yuan
Sustainability 2025, 17(15), 6973; https://doi.org/10.3390/su17156973 - 31 Jul 2025
Viewed by 331
Abstract
In rapidly urbanizing environments, environmental stressors—such as air pollution, noise, heat, and green space depletion—substantially exacerbate public health burdens, contributing to the global rise of non-communicable diseases, particularly hypertension, cardiovascular disorders, and mental health conditions. Despite expanding research on green spaces and health [...] Read more.
In rapidly urbanizing environments, environmental stressors—such as air pollution, noise, heat, and green space depletion—substantially exacerbate public health burdens, contributing to the global rise of non-communicable diseases, particularly hypertension, cardiovascular disorders, and mental health conditions. Despite expanding research on green spaces and health (+76.9%, 2019–2025) and optimization and algorithmic approaches (+63.7%), the compounded and synergistic impacts of these stressors remain inadequately explored or addressed within current urban planning frameworks. This study presents a Mixed Methods Systematic Review (MMSR) to investigate the potential of AI-driven urban design optimizations in mitigating these multi-scalar environmental health risks. Specifically, it explores the complex interactions between urbanization, traffic-related pollutants, green infrastructure, and architectural intelligence, identifying critical gaps in the integration of computational optimization with nature-based solutions (NBS). To empirically substantiate these theoretical insights, this study draws on longitudinal 24 h dynamic blood pressure (BP) monitoring (3–9 months), revealing that chronic exposure to environmental noise (mean 79.84 dB) increases cardiovascular risk by approximately 1.8-fold. BP data (average 132/76 mmHg), along with observed hypertensive spikes (systolic > 172 mmHg, diastolic ≤ 101 mmHg), underscore the inadequacy of current urban design strategies in mitigating health risks. Based on these findings, this paper advocates for the integration of AI-driven approaches to optimize urban environments, offering actionable recommendations for developing adaptive, human-centric, and health-responsive urban planning frameworks that enhance resilience and public health in the face of accelerating urbanization. Full article
(This article belongs to the Section Sustainable Urban and Rural Development)
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16 pages, 738 KiB  
Review
A Rationale for the Use of Ivabradine in the Perioperative Phase of Cardiac Surgery: A Review
by Christos E. Ballas, Christos S. Katsouras, Konstantinos C. Siaravas, Ioannis Tzourtzos, Amalia I. Moula and Christos Alexiou
J. Cardiovasc. Dev. Dis. 2025, 12(8), 294; https://doi.org/10.3390/jcdd12080294 - 31 Jul 2025
Viewed by 524
Abstract
This review explores the advantages of ivabradine in the management of cardiac surgery patients, particularly highlighting its heart rate (HR)-reducing properties, its role in minimizing the impact of atrial fibrillation, and its contributions to improving left ventricular diastolic function, as well as reducing [...] Read more.
This review explores the advantages of ivabradine in the management of cardiac surgery patients, particularly highlighting its heart rate (HR)-reducing properties, its role in minimizing the impact of atrial fibrillation, and its contributions to improving left ventricular diastolic function, as well as reducing pain, stress, and anxiety. In parallel, studies provide evidence that ivabradine influences endothelial inflammatory responses through mechanisms such as biomechanical modulation. Unlike traditional beta-blockers that may induce hypotension, ivabradine selectively inhibits hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, allowing for effective HR reduction without compromising blood pressure stability. This characteristic is particularly beneficial for patients at risk of atrial fibrillation post-surgery, where HR control is crucial for cardiovascular stability. This is an area in which ivabradine appears to play a role prophylactically, possibly in combination with beta-blockers. Furthermore, ivabradine has been associated with enhanced diastolic parameters in left ventricular function, reflecting its potential to improve surgical outcomes in patients with compromised heart function. In addition to its cardiovascular benefits, it appears to alleviate psychological stress and anxiety, common in postoperative settings, by moderating the neuroendocrine response to stress, thereby reducing stress-induced hormone levels. Furthermore, it has notable analgesic properties, contributing to pain management through its action on HCN channels in both the peripheral and central nervous systems. Collectively, these findings indicate that ivabradine may serve as a valuable therapeutic agent in the perioperative care of cardiac surgery patients, addressing both physiological and psychological challenges during recovery. Full article
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17 pages, 1682 KiB  
Review
High-Fructose-Induced Salt-Sensitive Hypertension: The Potential Benefit of SGLT4 or SGLT5 Modulation
by Sharif Hasan Siddiqui and Noreen F. Rossi
Nutrients 2025, 17(15), 2511; https://doi.org/10.3390/nu17152511 - 30 Jul 2025
Viewed by 248
Abstract
Hypertension is an important risk factor for cardiovascular diseases. High salt intake when consumed with excess fructose enhances hypertension and resultant cardiovascular disease. Usually, the small intestine absorbs dietary fructose, and the proximal tubule of kidney reabsorbs filtered fructose into the circulation with [...] Read more.
Hypertension is an important risk factor for cardiovascular diseases. High salt intake when consumed with excess fructose enhances hypertension and resultant cardiovascular disease. Usually, the small intestine absorbs dietary fructose, and the proximal tubule of kidney reabsorbs filtered fructose into the circulation with the help of different transporters including SGLT4 and SGLT5. Very recently, SGLT5 mRNA has also been found to be expressed in the heart. High-fructose diet stimulates the sympathetic nervous system and renin–angiotensin–aldosterone (RAAS) activity, of which both are responsible for endothelial dysfunction and are associated with salt-sensitive hypertension. Few studies exist regarding the effects of SGLT4 and SGLT5 on cardiovascular function and blood pressure. However, SGLT4 gene knockout does not alter fructose-associated impact on blood pressure. In contrast, blood pressure does not increase in SGLT5 knockout rats even during fructose consumption. Given that limiting fructose and salt consumption as a public health strategy has proven challenging, we hope that studies into SGLT4 and SGLT5 transporters will open new research initiatives to address salt-sensitive hypertension and cardiovascular disease. This review highlights current information about SGLT4 and SGLT5 on fructose absorption, salt-sensitive hypertension, cardiovascular disease and points the way for the development of therapeutic fructose inhibitors that limit adverse effects. Full article
(This article belongs to the Special Issue Effects of Nutrient Intake on Cardiovascular Disease)
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14 pages, 806 KiB  
Article
Beat-to-Beat Blood Pressure Monitoring and Orthostatic Hypotension-Related Falls in Two Cohorts of Older Adults
by Liping Wang, Eveline P. van Poelgeest, Marjolein Klop, Jurgen A. H. R. Claassen, Alfons G. Hoekstra and Nathalie van der Velde
Geriatrics 2025, 10(4), 102; https://doi.org/10.3390/geriatrics10040102 - 26 Jul 2025
Viewed by 259
Abstract
Background: Falls are a major public health issue among older adults, often related to postural or orthostatic hypotension (OH). The optimal timing and methods for measuring blood pressure (BP) to assess OH and its relationship with falls are uncertain. Methods: We analyzed data [...] Read more.
Background: Falls are a major public health issue among older adults, often related to postural or orthostatic hypotension (OH). The optimal timing and methods for measuring blood pressure (BP) to assess OH and its relationship with falls are uncertain. Methods: We analyzed data from two older cohorts: the PROHEALTH study (n = 30, aged ≥ 65 years) and the NILVAD-CBF trial (n = 58, aged ≥ 50 years). Continuous beat-to-beat BP was measured during active stand tests. We assessed orthostatic BP responses during sit-to-stand and supine-to-stand maneuvers and calculated the associations between orthostatic BP response variables and falls. Results: In the PROHEALTH cohort, participants with a history of falls exhibited a significantly lower baseline BP (115 ± 13/68 ± 10 vs. 142 ± 21/79 ± 11 mmHg; p = 0.004/0.018) and lower systolic BP (SBP) nadir (90 ± 22 vs. 112 ± 25 mmHg; p = 0.043) than non-fallers. SBP recovery within three minutes post-stand was delayed in fallers but rapid in non-fallers. A lower resting BP was associated with fall risk, and a lower BP nadir within 10 s after standing showed a trend toward a higher fall risk. No significant associations were found in the NILVAD-CBF cohort (prospective falls). Conclusions: Our findings demonstrate that a lower resting SBP and diastolic BP (DBP) are associated with an increased fall risk in older adults, with a lower SBP and DBP nadir after standing also showing a potential association. Persistent OH or delayed BP recovery is identified as a potentially relevant fall risk factor. The supine-to-stand test was more sensitive in detecting OH than the sit-to-stand test. Continuous BP monitoring provides the advantage of detecting pathophysiologic orthostatic BP responses for fall risk assessment in older adults. Further research with larger cohorts is warranted to validate our findings. Full article
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58 pages, 1238 KiB  
Review
The Collapse of Brain Clearance: Glymphatic-Venous Failure, Aquaporin-4 Breakdown, and AI-Empowered Precision Neurotherapeutics in Intracranial Hypertension
by Matei Șerban, Corneliu Toader and Răzvan-Adrian Covache-Busuioc
Int. J. Mol. Sci. 2025, 26(15), 7223; https://doi.org/10.3390/ijms26157223 - 25 Jul 2025
Viewed by 379
Abstract
Although intracranial hypertension (ICH) has traditionally been framed as simply a numerical escalation of intracranial pressure (ICP) and usually dealt with in its clinical form and not in terms of its complex underlying pathophysiology, an emerging body of evidence indicates that ICH is [...] Read more.
Although intracranial hypertension (ICH) has traditionally been framed as simply a numerical escalation of intracranial pressure (ICP) and usually dealt with in its clinical form and not in terms of its complex underlying pathophysiology, an emerging body of evidence indicates that ICH is not simply an elevated ICP process but a complex process of molecular dysregulation, glymphatic dysfunction, and neurovascular insufficiency. Our aim in this paper is to provide a complete synthesis of all the new thinking that is occurring in this space, primarily on the intersection of glymphatic dysfunction and cerebral vein physiology. The aspiration is to review how glymphatic dysfunction, largely secondary to aquaporin-4 (AQP4) dysfunction, can lead to delayed cerebrospinal fluid (CSF) clearance and thus the accumulation of extravascular fluid resulting in elevated ICP. A range of other factors such as oxidative stress, endothelin-1, and neuroinflammation seem to significantly impair cerebral autoregulation, making ICH challenging to manage. Combining recent studies, we intend to provide a revised conceptualization of ICH that recognizes the nuance and complexity of ICH that is understated by previous models. We wish to also address novel diagnostics aimed at better capturing the dynamic nature of ICH. Recent advances in non-invasive imaging (i.e., 4D flow MRI and dynamic contrast-enhanced MRI; DCE-MRI) allow for better visualization of dynamic changes to the glymphatic and cerebral blood flow (CBF) system. Finally, wearable ICP monitors and AI-assisted diagnostics will create opportunities for these continuous and real-time assessments, especially in limited resource settings. Our goal is to provide examples of opportunities that exist that might augment early recognition and improve personalized care while ensuring we realize practical challenges and limitations. We also consider what may be therapeutically possible now and in the future. Therapeutic opportunities discussed include CRISPR-based gene editing aimed at restoring AQP4 function, nano-robotics aimed at drug targeting, and bioelectronic devices purposed for ICP modulation. Certainly, these proposals are innovative in nature but will require ethically responsible confirmation of long-term safety and availability, particularly to low- and middle-income countries (LMICs), where the burdens of secondary ICH remain preeminent. Throughout the review, we will be restrained to a balanced pursuit of innovative ideas and ethical considerations to attain global health equity. It is not our intent to provide unequivocal answers, but instead to encourage informed discussions at the intersections of research, clinical practice, and the public health field. We hope this review may stimulate further discussion about ICH and highlight research opportunities to conduct translational research in modern neuroscience with real, approachable, and patient-centered care. Full article
(This article belongs to the Special Issue Latest Review Papers in Molecular Neurobiology 2025)
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13 pages, 1449 KiB  
Article
Cardiocirculatory and Metabolic Responses to Low- and High-Load Squat Exercise in Young and Middle-Aged Individuals
by Alessandro L. Colosio, Massimo Teso, Alberto Bottari, Luca Ferrari, Gianluca Bochicchio, Jan Boone and Silvia Pogliaghi
J. Funct. Morphol. Kinesiol. 2025, 10(3), 287; https://doi.org/10.3390/jfmk10030287 - 25 Jul 2025
Viewed by 409
Abstract
Objectives: The aim of this study was to assess the safety and feasibility of resistance training (RT) in middle-aged and young individuals by examining cardiocirculatory and metabolic responses to squat performed under low and high external loads as per current exercise prescription [...] Read more.
Objectives: The aim of this study was to assess the safety and feasibility of resistance training (RT) in middle-aged and young individuals by examining cardiocirculatory and metabolic responses to squat performed under low and high external loads as per current exercise prescription guidelines. Methods: Eighteen RT-trained individuals (nine middle-aged individuals, including eight women who were equally distributed) performed a cycling incremental test for the determination of their maximal aerobic capacity and three sessions of RT, respectively, to determine their one repetition maximum (1RM) of squat and their physiological responses during different training protocols of squat with equal training loads (3 × 12 at 55% 1RM vs. 5 × 5 at 80% 1RM). Whole-body metabolic (oxygen update and blood lactate) and cardiocirculatory (heart rate and blood pressure) responses and rate of perceived exertion (RPE) were compared across age groups and % 1RM to determine the metabolic stimulus and cardiovascular strain imposed by this form of training. Results: Young and middle-aged individuals exhibited similar cardiocirculatory responses to RT, with the only exception being a higher diastolic response in the middle-aged group for both protocols (present also at rest). No difference was found between the two age groups in terms of metabolic response and RPE. 80% 1RM induced a similar cardiocirculatory response and a higher RPE but a lower metabolic response compared to 55% 1RM. Conclusions: While no difference in physiological responses was found between the groups, the lower-load and higher-repetition training scheme demonstrated better time efficiency, metabolic activation, and perceived effort with equivalent cardiocirculatory strain. These findings support the safety of RT and can guide practitioners in the design of training protocols. Full article
(This article belongs to the Section Sports Medicine and Nutrition)
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22 pages, 5657 KiB  
Article
SUL-150 Limits Vascular Remodeling and Ventricular Failure in Pulmonary Arterial Hypertension
by Lysanne M. Jorna, Dalibor Nakládal, Johannes N. van Heuveln, Diederik E. van der Feen, Quint A. J. Hagdorn, Guido P. L. Bossers, Annemieke van Oosten, Michel Weij, Ludmila Tkáčiková, Soňa Tkáčiková, Robert H. Henning, Martin C. Harmsen, Rolf M. F. Berger and Guido Krenning
Int. J. Mol. Sci. 2025, 26(15), 7181; https://doi.org/10.3390/ijms26157181 - 25 Jul 2025
Viewed by 268
Abstract
Pulmonary arterial hypertension (PAH) is a rare, progressive, and incurable disease characterized by an elevated pulmonary blood pressure, extensive remodeling of the pulmonary vasculature, increased pulmonary vascular resistance, and culminating in right ventricular failure. Mitochondrial dysfunction has a major role in the pathogenesis [...] Read more.
Pulmonary arterial hypertension (PAH) is a rare, progressive, and incurable disease characterized by an elevated pulmonary blood pressure, extensive remodeling of the pulmonary vasculature, increased pulmonary vascular resistance, and culminating in right ventricular failure. Mitochondrial dysfunction has a major role in the pathogenesis of PAH and secondary right ventricular failure, and its targeting may offer therapeutic benefit. In this study, we provide proof-of-concept for the use of the mitochondrially active drug SUL-150 to treat PAH. PAH was induced in rats by monocrotaline, followed by the placement of an aortocaval shunt one week later. The mitoprotective compound SUL-150 (~6 mg·kg−1·day−1) or vehicle was administered intraperitoneally via osmotic minipump for 28 days, implanted at the time of aortocaval shunt placement. Vehicle-treated PAH rats had dyspnea and showed pulmonary artery remodeling with increased responsiveness to phenylephrine, in addition to remodeling of the intrapulmonary arterioles. SUL-150 administration mitigated the dyspnea and the remodeling responses. Vehicle-treated PAH rats developed right ventricular hypertrophy, fibrosis, and failure. SUL-150 administration precluded cardiomyocyte hypertrophy and inhibited ventricular fibrogenesis. Right ventricular failure in vehicle-treated PAH rats induced mitochondrial loss and dysfunction associated with a decrease in mitophagy. SUL-150 was unable to prevent the mitochondrial loss but improved mitochondrial health in the right ventricle, which culminated in the preservation of right ventricular function. We conclude that SUL-150 improves PAH-associated morbidity by the amelioration of pulmonary vascular remodeling and right ventricular failure and may be considered a promising therapeutic candidate to slow disease progression in pulmonary arterial hypertension and secondary right ventricular failure. Full article
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10 pages, 439 KiB  
Article
Comparison of Angiotensin II (Giapreza®) Use in Kidney Transplantation Between Black and Non-Black Patients
by Michelle Tsai, Jamie Benken, Joshua Adisumarta, Eleanor Anderson, Chris Cheng, Adriana Ortiz, Enrico Benedetti, Hokuto Nishioka and Scott Benken
Biomedicines 2025, 13(8), 1819; https://doi.org/10.3390/biomedicines13081819 - 24 Jul 2025
Viewed by 378
Abstract
Background/Objectives: Perioperative hypotension during kidney transplantation poses a risk to graft function and survival. Angiotensin II (AngII) is an endogenous vasoconstrictor targeting the renin–angiotensin–aldosterone system (RAAS) to increase blood pressure. Black patients may have a different response to synthetic angiotensin II (AT2S) [...] Read more.
Background/Objectives: Perioperative hypotension during kidney transplantation poses a risk to graft function and survival. Angiotensin II (AngII) is an endogenous vasoconstrictor targeting the renin–angiotensin–aldosterone system (RAAS) to increase blood pressure. Black patients may have a different response to synthetic angiotensin II (AT2S) compared to non-Black patients, given differential expressions in renin profiles. The purpose of this study is to assess the difference between Black and non-Black patients in total vasopressor duration and usage when AT2S is first line for hypotension during kidney transplantation. Methods: A single-center, retrospective cohort study comparing Black and non-Black patients who required AT2S as a first-line vasopressor for hypotension during the perioperative period of kidney transplantation. Results: The primary outcome evaluating total usage of vasopressors found that Black patients required longer durations of vasopressors (36.9 ± 66.8 h vs. 23.7 ± 31.7 h; p = 0.022) but no difference in vasopressor amount (0.07 ± 0.1 NEE vs. 0.05 ± 0.1 NEE; p = 0.128) compared to non-Black patients. Regression analysis found that body weight was associated with the duration of vasopressors (p < 0.05), while baseline systolic blood pressure was inversely associated with it. Longer duration of vasopressors and duration of transplant surgery were associated with delayed graft function in regression analysis (p < 0.05). Conclusions: Black patients had a longer duration of vasopressors, but this was not driven by differences in usage of AT2S. As baseline weight was significantly higher in Black patients and associated with duration of usage, perhaps the metabolic differences in our Black patients led to the observed differences. Regardless, longer durations of vasopressors were associated with delayed graft function, making this an area of utmost importance for continued investigation. Full article
(This article belongs to the Section Drug Discovery, Development and Delivery)
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20 pages, 3249 KiB  
Article
Granulocyte-Macrophage Colony-Stimulating Factor Inhibition Ameliorates Innate Immune Cell Activation, Inflammation, and Salt-Sensitive Hypertension
by Hannah L. Smith, Bethany L. Goodlett, Gabriella C. Peterson, Emily N. Zamora, Ava R. Gostomski and Brett M. Mitchell
Cells 2025, 14(15), 1144; https://doi.org/10.3390/cells14151144 - 24 Jul 2025
Viewed by 356
Abstract
Hypertension (HTN) is a major contributor to global morbidity and manifests in several variants, including salt-sensitive hypertension (SSHTN). SSHTN is defined by an increase in blood pressure (BP) in response to high dietary salt, and is associated with heightened cardiovascular risk, renal damage, [...] Read more.
Hypertension (HTN) is a major contributor to global morbidity and manifests in several variants, including salt-sensitive hypertension (SSHTN). SSHTN is defined by an increase in blood pressure (BP) in response to high dietary salt, and is associated with heightened cardiovascular risk, renal damage, and immune system activation. However, the role of granulocyte-macrophage colony-stimulating factor (GM-CSF) has not yet been explored in the context of SSHTN. Previously, we reported that GM-CSF is critical in priming bone marrow-derived (BMD)-macrophages (BMD-Macs) and BMD-dendritic cells (BMD-DCs) to become activated (CD38+) in response to salt. Further exploration revealed these cells differentiated into BMD-M1 Macs, CD38+ BMD-M1 Macs, BMD-type-2 conventional DCs (cDC2s), and CD38+ BMD-cDC2s. Additionally, BMD-monocytes (BMDMs) grown with GM-CSF and injected into SSHTN mice traffic to the kidneys and differentiate into Macs, CD38+ Macs, DCs, and CD38+ DCs. In the current study, we treated SSHTN mice with an anti-GM-CSF antibody (aGM) and found that preventive aGM treatment mitigated BP, prevented renal inflammation, and altered renal immune cells. In mice with established SSHTN, aGM treatment attenuated BP, reduced renal inflammation, and differentially affected renal immune cells. Adoptive transfer of aGM-treated BMDMs into SSHTN mice resulted in decreased renal trafficking. Additionally, aGM treatment of BMD-Macs, CD38+ BMD-M1 Macs, BMD-DCs, and CD38+ BMD-cDC2s led to decreased pro-inflammatory gene expression. These findings suggest that GM-CSF plays a role in SSHTN and may serve as a potential therapeutic target. Full article
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13 pages, 2474 KiB  
Article
Renal Effects and Nitric Oxide Response Induced by Bothrops atrox Snake Venom in an Isolated Perfused Kidney Model
by Terentia Batista Sa Norões, Antonio Rafael Coelho Jorge, Helena Serra Azul Monteiro, Ricardo Parente Garcia Vieira and Breno De Sá Barreto Macêdo
Toxins 2025, 17(8), 363; https://doi.org/10.3390/toxins17080363 - 24 Jul 2025
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Abstract
The snakes from the genus Bothrops are responsible for most of the ophidic accidents in Brazil, and Bothrops atrox represents one of these species. Envenomation by these snakes results in systemic effects and is often associated with early mortality following snakebite incidents. The [...] Read more.
The snakes from the genus Bothrops are responsible for most of the ophidic accidents in Brazil, and Bothrops atrox represents one of these species. Envenomation by these snakes results in systemic effects and is often associated with early mortality following snakebite incidents. The present study investigates the pharmacological properties of Bothrops atrox venom (VBA), focusing specifically on its impact on renal blood flow. Following the renal perfusion procedure, kidney tissues were processed for histopathological examination. Statistical analysis of all evaluated parameters was conducted using ANOVA and Student’s t-test, with significance set at p < 0.005. Administration of VBA resulted in a marked reduction in both perfusion pressure and renal vascular resistance. In contrast, there was a significant elevation in urinary output and glomerular filtration rate. Histological changes observed in the perfused kidneys were mild. The involvement of nitric oxide in the pressor effects of Bothrops atrox venom was not investigated in renal perfusion systems or in in vivo models. Treatment with VBA led to elevated nitrite levels in the bloodstream of the experimental animals. This effect was completely inhibited following pharmacological blockade with L-NAME. Based on these findings, we conclude that VBA alters renal function and promotes increased nitric oxide production. Full article
(This article belongs to the Special Issue Clinical Evidence for Therapeutic Effects and Safety of Animal Venoms)
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11 pages, 275 KiB  
Article
Cardiovascular and Functional Consequences of Lung Function Impairment in Northern Thai Agricultural Workers
by Anurak Wongta, Muhammad Samar, Nan Ei Moh Moh Kyi, Tipsuda Pintakham, Nootchakarn Sawarng and Surat Hongsibsong
Int. J. Environ. Res. Public Health 2025, 22(8), 1168; https://doi.org/10.3390/ijerph22081168 - 23 Jul 2025
Viewed by 309
Abstract
In low- and middle-income countries, notably in rural agricultural populations exposed to environmental and occupational dangers, respiratory impairment and noncommunicable diseases (NCDs) are major public health issues. This cross-sectional study examined the associations between lung function, functional capacity, and cardiovascular responses to the [...] Read more.
In low- and middle-income countries, notably in rural agricultural populations exposed to environmental and occupational dangers, respiratory impairment and noncommunicable diseases (NCDs) are major public health issues. This cross-sectional study examined the associations between lung function, functional capacity, and cardiovascular responses to the Six-Minute Walk Test (6MWT) in 137 adults from San Pa Tong District, Northern Thailand. Lung function was assessed using spirometry, and participants were classified accordingly. Hemodynamic parameters, including blood pressure, heart rate, rate-pressure product, and oxygen saturation, were measured before and after the 6MWT. Participants with impaired lung function walked significantly shorter distances (p = 0.004), and walking distance was positively correlated with forced vital capacity (FVC) and forced expiratory volume in one second (FEV1). Logistic regression confirmed that walking distance independently predicted lung function impairment after adjusting for age and sex. Cardiovascular responses to exercise also varied significantly across demographic subgroups. These findings support the use of the 6MWT as a practical, cost-effective, and scalable method for detecting lung function impairments in resource-limited rural settings. To our knowledge, this is among the first studies to demonstrate the predictive value of the 6MWT for lung function impairment in a Southeast Asian agricultural population. Full article
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