Publications

Showing 61–80 of 2058 publications.

• Vorticity-Facilitated Platelet Aggregation: a High Expansion-Ratio Stenotic Microfluidic Platform Unravels the Role of Complex Flow Dynamics in Arterial Thrombosis
  Ren, Jianfang; Abidin, Nurul Aisha Zainal; Sun, Allan; Gao, Rui; Chen, Yuxin; Nasser, Arian; Wang, Zihao; Zhao, Yunduo Charles; Dupuy, Alexander; Waterhouse, Anna; Su, Qian Peter; Vigolo, Daniele; Wu, Mike C.L.; Ju, Lining Arnold
  Advanced Healthcare Materials (Vol. 14/28) – 2025
  Complex flow patterns play a critical role in arterial thrombosis, yet the specific contribution of vorticitythe rotational component of fluid flowremains poorly understood. An innovative microfluidic platform with systematically varied expansion angles (? = 30-150) in a double stenosis design is developed to isolate vorticity's effects under controlled conditions. The high expansion-ratio device with sharp-angled geometries successfully generates distinct vortical flow patterns, confirmed through computational and experimental flow visualizations. Real-time confocal microscopy revealed a strong positive correlation (r = 0.6698) between vorticity magnitude and thrombus size, with high-vorticity conditions producing thrombi up to four times larger than low-vorticity settings. Mechanistic investigations demonstrated enhanced von Willebrand Factor (vWF) accumulation and platelet integrin activation in vortical environments. Platelets in high-vorticity regions exhibited integrin ?<inf>IIb</inf>?<inf>3</inf> intermediate activation states with significantly enhanced calcium signaling, suggesting vorticity amplifies platelet mechanosensing pathways. Inhibition of the interaction between vWF and platelet glycoprotein Ib? (GPIb?) receptor abolished biomechanical platelet aggregation in vortical regions. These findings provide valuable insights into platelet thrombosis in complex flow environments with significant implications for optimizing medical devices to minimize thrombotic complications associated with vortex formation. 2025 The Author(s). Advanced Healthcare Materials published by Wiley-VCH GmbH.
• Cachexia and Wasting in Chronic Illness: Regulatory and Clinical Trial Update
  Fioretti, Francesco; von Haehling, Stephan; Coats, Andrew J.S.; Butler, Javed J.; del Fabbro, Egidio G.; Skipworth, Richard J.E.; Laird, Barry J.A.; Anker, Stefan D.
  Journal of Cachexia, Sarcopenia and Muscle (Vol. 16/6) – 2025
  Cachexia, a syndrome marked by nonintentional weight loss, muscle wasting, functional decline and poor prognosis, affects 50%80% of cancer patients, severely impacting quality of life, treatment tolerance and survival. A Regulatory and Trial Update Workshop was organized by the Society on Cachexia and Wasting Disorders (SCWD) in December 2024 in Washington, DC, focused on clinical trial endpoints, standards of care and recent advancements. This article provides a summary of the discussions that were held during the first day of the workshop. Despite ongoing research, effective therapies for cachexia remain limited. Existing treatments, such as nutritional supplements, progestins, anti-inflammatories and anabolic agents, have shown mixed results, often improving appetite or lean mass without consistent functional benefits. Common muscle mass measurements, like CT scans of the L3 vertebra, are inadequate as primary endpoints because of biological variability and small effect sizes and because they do not necessarily translate into clinical benefit. Trials continue to face challenges in meeting regulatory requirements, which mandate improvements in both body composition and functional outcomes. Regulatory consensus emphasizes demonstrating clinically meaningful benefits in patient-reported outcomes/physical function and/or morbiditymortality using validated instruments, adequate safety exposure, recognition that handgrip and weight alone are insufficient, feasibility in advanced disease, consideration of general activity measures, optional but informative body composition data and, for a pan-cancer label, benefits across at least three distinct cancers. Patient-centred endpoints, emphasizing real-life functioning and social participation, are essential as patients prioritize daily activity and independence over isolated physical measures. Clinical trials presented during the meeting included the MENAC trial, which tested a multimodal intervention combining nutrition, exercise, anti-inflammatory drugs and cancer therapy, achieved modest weight stabilization but no significant improvements in muscle mass or activity. In contrast, TCMCB07, an MC-4 receptor antagonist, demonstrated promising results in preclinical and early-phase human studies, showing weight stabilization and improved caloric intake with good tolerability. ART27.13, a dual CB1/CB2 receptor agonist, also demonstrated positive effects in appetite stimulation and weight stabilization. For S-pindolol, which targets appetite and metabolism, Phase IIb/III trials are to be initiated, following an earlier Phase II trial that showed improved muscle mass and muscle strength (hand grip strength). Future treatments must focus on integrating patient-centred goals, therapeutic mechanisms and meaningful clinical outcomes. 2025 The Author(s). Journal of Cachexia, Sarcopenia and Muscle published by Wiley Periodicals LLC.
• Neutrophil Membrane Tether Coalescence: A Novel Mechanoadaptive Response to Abrupt Flow Acceleration
  Moldovan, Laura; Sun, Allan; Huang, Tao; Wang, Yao; Wang, Haoqing Jerry; Song, Haoran Caroline; Su, Qian Peter; Ju, Lining Arnold
  Advanced NanoBiomed Research (Vol. 5/12) – 2025
  Neutrophils navigating the vasculature encounter regions of abrupt flow acceleration that challenge their adhesive capacity. Here, a previously uncharacterized mechanoadaptive response that enables neutrophils to maintain adhesion under these challenging conditions is revealed. Using microfluidic systems to precisely control flow dynamics, it is demonstrated that neutrophils respond differently to steady versus accelerating flow (delta shear) conditions. While steady-increasing flow induces formation of multiple discrete tethers, abrupt acceleration triggers their coalescence into thicker, mechanically robust structures that significantly enhance adhesion stability. Through Machine Intelligent Structured Illumination Microscopy with exceptional spatiotemporal resolution, the nanoscale dynamics of this coalescence process is characterized, revealing that despite extensive membrane remodeling, the original anchor points of adhesion molecules remain spatially fixed. Dual-color spinning total internal reflection fluorescence imaging shows targeted accumulation of F-actin at the cell tongue, providing critical mechanical support. Differential effects of actin-disrupting agents confirm that tether coalescence depends on intact cytoskeletal structures rather than active polymerization. This membrane adaptation represents a sophisticated strategy enabling neutrophils to withstand high detachment forces in disturbed flow environments characteristic of vascular bifurcations, stenoses, and device-associated thromboinflammation. These findings advance understanding of neutrophil mechanobiology and may inform therapeutic strategies targeting pathological neutrophil adhesion without compromising essential immune functions. 2025 The Author(s). Advanced NanoBiomed Research published by Wiley-VCH GmbH.
• Platelet derived growth factor-AB modulates post-infarct myocardium leading to extended improvement in cardiac function
  Deshmukh, Tejas; Hume, Robert D.; Chen, Siqi; Igoor, Sindhu; Foster, Sheryl L.; Barry, Tony; Lu, Juntang; Tran, Vu Toan; Pouliopoulos, Jim; Jabbour, Andrew; Vigder, Niv; Cordwell, Stuart James; Tumanov, Sergey; Nguyen, Christopher T.; Kotake, Yasuhito; Turnbull, Samual; Campbell, Timothy G.; Pathan, Faraz K.; Kumar, Saurabh; Kizana, Eddy; Chong, James J.H.
  npj Regenerative Medicine (Vol. 10/1) – 2025
  Myocardial infarction (MI) contributes to significant morbidity and mortality globally. Platelet derived growth factor-AB (PDGF-AB) is potentially a novel translational therapeutic for improving cardiac function post-MI, which we assess here using a 60 day porcine left anterior descending artery occlusion ischemia-reperfusion model. MI was induced in 10 female Landrace swine, with 5 controls, 5 receiving PDGF-AB treatment and 2 additional shams. PDGF-AB improved left ventricular ejection fraction 58 days after MI, without affecting overall infarct scar size, as shown using serial cardiac magnetic resonance imaging. Preserved infarct zone microvascular function and increased vessel maturity was also observed. Multi-omic analyses showed that PDGF-AB treatment altered the expression of proteins, metabolites, and lipids that are known to be involved in myocardial energetics and redox balance. Novel therapeutics such as PDGF-AB may lead to more sustained salvage of cardiac function by modulating the post-MI microvasculature, myocardium and extracellular matrix. The Author(s) 2025.
• Protein biosensors of heart failure biomarker S100A7
  Mutschler, Roxane; Caputo, Alessandro T.; Guo, Zhong; Liew, Yijin; Fiorito, Maria M.; Newton, Sophia; Zhang, Xi; Karunathilaka, Nuwan; Chan, Wandy Y.Wandy; Kostner, Karam Maximilien; Korczyk, Dariusz P.; Atherton, John James; Coates, Andrew J.S.; Punyadeera, Chamindie K.; Kirill Alexandrov, Kirill A.; Cui, Zhenling
  Biosensors and Bioelectronics: X (Vol. 27) – 2025
  Artificial allosteric protein switches (biosensors) hold the promise to deliver disruptive analytical and diagnostic applications. However, their construction is complicated by the limited availability of selective receptor domains. Here, we report the use of mRNA display to rapidly select FN3con-based binding domains to S100A7 protein - a biomarker of heart failure. The crystal structure of the resulting FN3con binding domain in complex with S100A7 dimer revealed that the binding interface of the dimer is formed by similar, but not identical, side-chain interaction networks. Using medium-throughput functional screening, we tested selected binding domains for compatibility with two protein biosensor architectures. The best biosensor demonstrated a dynamic range of 57-fold and a 1 nM limit of detection and was used to establish a rapid homogeneous assay for quantification of S100A7 in clinical saliva samples. The assay was able to distinguish heart failure patient samples from those of healthy donors. Our results demonstrate that mRNA binding domain development and biosensor prototyping pipelines can deliver practically useful biosensors to potentially any target. 2025 The Authors
• An Indigenous data analysis framework of practice and Carmens Theory
  Parter, Carmen; Brown, Shae L.; Rix, Elizabeth Florence; Wilson, Shawn
  AlterNative (Vol. 21/4) – 2025
  This article addresses a significant gap in our scholarly knowledge concerning the use of Indigenous ways of being, knowing, and doing, in research data analysis, when applying Indigenous philosophies and research methodologies. Often as Indigenous researchers when applying an Indigenous paradigm, standpoint, methodology and methods, we tend to revert to non-Indigenous western science approaches to the data analysis process, which was the case for first author Carmen when she was undertaking her Doctor of Philosophy and applied thematic analysis. To avoid conflicts between the use of the ologies, that is, ways of being, knowing, and doing, that are evident between Indigenous and western sciences we provide an Indigenist data analysis framework. This work adds value to scholarly knowledge by providing a way to maintain our Indigenous ways of being, knowing, and doing, during the data analysis research process, as we continue to restore our Indigeneity when applying an Indigenist paradigm and standpoint. The Author(s) 2025. This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).
• Reduced PI3K(p110?) induces atrial myopathy, and PI3K-related lipids are dysregulated in athletes with atrial fibrillation
  Bass-Stringer, Sebastian; Bernardo, Bianca C.; Yildiz, Gunes S.; Matsumoto, Aya; Kiriazis, Helen; Harmawan, Claudia A.; Tai, Celeste M.K.; Chooi, Roger; Bottrell, Lauren; Ezeani, Martin; Donner, Daniel G.; D'Elia, Aascha A.; Ooi, Jenny Y. Y.; Mellett, Natalie Ann; Luo, Jieting; Masterman, Emma I.; Janssens, Kristel; Olshansky, Gavriel; Howden, Erin J.; Cross, Jonathon H.; Hagemeyer, Christoph Eugen; Lin, Ruby CY; Thomas, Colleen J.; Magor, Graham W.; Perkins, Andrew Charles; Marwick, Thomas H.; Kawakami, Hiroshi; Meikle, Peter J.; Greening, David W.; Weeks, Kate L.; La Gerche, AndrCrossed D.Sign; Tham, Yow Keat; McMullen, Julie R.
  Journal of Sport and Health Science (Vol. 14) – 2025
  Background: Elucidating mechanisms underlying atrial myopathy, which predisposes individuals to atrial fibrillation (AF), will be critical for preventing/treating AF. In a serendipitous discovery, we identified atrial enlargement, fibrosis, and thrombi in mice with reduced phosphoinositide 3-kinase (PI3K) in cardiomyocytes. PI3K(p110?) is elevated in the heart with exercise and is critical for exercise-induced ventricular enlargement and protection, but the role in the atria was unknown. Physical inactivity and extreme endurance exercise can increase AF risk. Therefore, our objective was to investigate whether too little and/or too much PI3K alone induces cardiac pathology. Methods: New cardiomyocyte-specific transgenic mice with increased or decreased PI3K(p110?) activity were generated. Multi-omics was conducted in mouse atrial tissue, and lipidomics in human plasma. Results: Elevated PI3K led to an increase in heart size with preserved/enhanced function. Reduced PI3K led to atrial dysfunction, fibrosis, arrhythmia, increased susceptibility to atrial enlargement and thrombi, and dysregulation of monosialodihexosylganglioside (GM3), a lipid that regulates insulin-like growth factor-1 (IGF1)PI3K signaling. Proteomic profiling identified distinct signatures and signaling networks across atria with varying degrees of dysfunction, enlargement, and thrombi, including commonalities with the human AF proteome. PI3K-related lipids were dysregulated in plasma from athletes with AF. Conclusion: PI3K(p110?) is a critical regulator of atrial biology and function in mice. This work provides a proteomic resource of candidates for further validation as potential new drug targets and biomarkers for atrial myopathy. Further investigation of PI3K-related lipids as markers for identifying individuals at risk of AF is warranted. Dysregulation of PI3K may contribute to the association between increased cardiac risk with physical inactivity and extreme endurance exercise. 2025
• The FKBPL-based therapeutic peptide, AD-01, protects the endothelium from hypoxia-induced damage by stabilising hypoxia inducible factor-? and inflammation
  Ghorbanpour, Sahar Masoumeh; Cartland, Si; Chen, Hao; Seth, Sanchit; Ecker, Rupert Ch; Richards, Claire; Aksentijevi?, Dunja; Padula, Matthew P.; Cole, Louise; Ebrahimi Warkiani, Majid; Kavurma, Mary M.; McClements, Lana
  Journal of Translational Medicine (Vol. 23/1) – 2025
  Background: Endothelial dysfunction is a hallmark feature of cardiovascular disease (CVD), yet the underlying mechanisms are still poorly understood. This has impeded the development of effective therapies, particularly for peripheral artery disease. FK506-binding protein like (FKBPL) and its therapeutic peptide mimetic, AD-01, are crucial negative regulators of angiogenesis, however their roles in CVD are unknown. In this study, we aimed to elucidate the FKBPL-mediated mechanisms involved in regulating endothelial dysfunction induced by hypoxia or inflammation, and to determine whether AD-01 can effectively restore endothelial function under these conditions. Methods: Hindlimb ischemia was induced in mice by ligating the proximal and distal ends of the right femoral artery, and, after three days, the gastrocnemius muscle was collected for immunofluorescence staining, and RNA extraction. A 3D in vitro microfluidics model was developed to determine the endothelial cell migration and impact of FKBPL following treatments with: (i) 24 M FKBPL targeted siRNA, (ii) 1 mM hypoxia inducible factor (HIF-1)? activator (DMOG), (iii) 50% (v/v) macrophage conditioned media (MCM), 100 nM AD-01. Unbiased, untargeted proteomic analysis was conducted via LC-MS/MS to identify protein targets of AD-01. Results: FKBPL expression is substantially downregulated in mice after hindlimb ischemia (p < 0.05, protein; p < 0.001, mRNA), correlating with increased neovascularization and altered vascular adhesion molecule expression. In our real-time advanced 3D microfluidics model, hypoxia suppressed FKBPL (p < 0.05) and VE-cadherin (p < 0.001) expression, leading to increased endothelial cell number and migration (p < 0.001), which was restored by AD-01 treatment (p < 0.01). Under inflammatory conditions, FKBPL (p < 0.01) and HIF-1? (p < 0.05) expression was elevated, correlating with increased endothelial cell migration (p < 0.05). Unlike hypoxia, AD-01 did not influence endothelial cell migration under inflammatory conditions, but normalized FKBPL (p < 0.001), HIF-1? (p < 0.05) and CD31 (P < 0.05), expression, in 3D microfluidic cell culture. Proteomic analysis revealed that AD-01 treatment in hypoxia enhanced the abundance of tissue remodelling and vascular integrity proteins including collagen alpha-1(XIX) chain and junctional cadherin associated-5 (JCAD) proteins. Conclusions: FKBPL represents an important novel mechanism in hypoxia and inflammation-induced angiogenesis. The FKBPL-based therapeutic peptide, AD-01, could be a viable treatment option for CVD-related endothelial cell dysfunction. The Author(s) 2025.
• Toward strategies to advance the conductive properties of hydrogel formulations for cardiac tissue engineering
  Al Shamery, Wafa; Gentile, Carmine
  iScience (Vol. 28/11) – 2025
  This review article aims to elucidate the role of conductive polymers (CPs) in cardiac bioengineering, focusing on scaffolds and biomaterials required for cardiac tissue engineering. It explores the unique features of CPs that make them well-suited for biomedical applications and explores how these polymers have been optimized to exhibit these properties. Moreover, the review provides insight into the importance of conductive biomaterials and their applications for cardiac repair and regeneration. Furthermore, the review seeks to inform and guide readers in this evolving field, highlighting the significant potential of conductive biomaterials in advancing cardiac tissue engineering. By understanding the capabilities and optimization strategies of CPs, researchers can effectively utilize these materials to develop innovative therapies for myocardial repair and regeneration, ultimately contributing to improved outcomes for patients suffering from heart attacks. 2025 The Author(s)
• P selectin promotes SARS-CoV-2 interactions with platelets and the endothelium
  Moreno, Cesar Llogari; Castanheira, Fernanda V.S.; Ospina Stella, Alberto Ospina; Chung, Felicity; Aggarwal, Anupriya; Cole, Alexander J.; Loo, Lipin; Dupuy, Alexander; Kong, Yvonne X.; Hagimola, Lejla; Fenwick, Jemma C.L.; Coleman, Paul R.; Carr, Rebecca; Du, Tian Y.; Ison, Timothy; Newton, Michelle; Bui-Marinos, Maxwell P.; Cohen, Scott B.; Corcoran, Jennifer A.; Hesselson, Daniel; Gamble, Jennifer R.; Passam, Freda H.; Turville, Stuart G.; Kubes, Paul; Neely, G. Gregory
  Journal of Clinical Investigation (Vol. 135/22) – 2025
  The physiology of SARS-CoV-2 virus/host interactions is not well understood. To better understand host/virus interactions, we performed a CRISPR activation screen to identify host genes that confer resistance to authentic SARS-CoV-2. This highlighted 34 new candidate genes that may alter the course of infection. We validated that 7 of these genes can suppress authentic SARS-CoV-2 infection, including the innate immune receptor P selectin, which increases SARS-CoV-2 spikedependent binding to cells, while protecting from infection. P selectin also promotes binding to SARS-CoV-2 variants, SARSCoV- 1, and Middle East respiratory syndrome spike proteins, suggesting a general role for P selectin in highly pathogenic coronavirus infections. Importantly, P selectin protein expression driven by synthetic mRNA can block SARS-CoV-2 infection. Naturally, P selectin is expressed on platelets, and we show that it promotes spike-mediated platelet aggregation. P selectin is also expressed on the endothelium, where SARS-CoV-2 spike interactions are also P selectin dependent. In vivo, SARSCoV- 2 uses P selectin to home to capillary beds where the virus interacts with platelets and endothelium, and blocking this interaction can clear vascular-associated pulmonary SARS-CoV-2. 2025, Moreno et al. This is an open access article published under the terms of the Creative Commons Attribution 4.0 International License.
• Targeting vascular adhesion protein-1 and myeloperoxidase with a dual inhibitor SNT-8370 in preclinical models of inflammatory disease
  Glaros, Elias N.; Foot, Jonathan S.; Rayner, Benjamin Saul; Schilter, Heidi; Zhang, Yunjia; Paumann-Page, Martina E.; Teixeira, Mauro Martins; Jarolimek, Wolfgang; Thomas, Shane R.
  Nature Communications (Vol. 16/1) – 2025
  Inflammatory diseases are a major source of morbidity and mortality world-wide, the pathogenesis of which are characterised by the interplay of key pro-inflammatory and oxidative enzymes. Here, we report the development of a small molecule dual inhibitor targeting vascular adhesion protein-1 (VAP-1) and myeloperoxidase (MPO), two clinically relevant pro-inflammatory/oxidative enzymes that play complementary pathogenic roles in various inflammatory diseases. This agent, SNT-8370 [(E)-3-(3-((2-(aminomethyl)-3-fluoroallyl)oxy)benzyl)-2-thioxo-1,2,3,7-tetrahydro-6H-purin-6-one)], irreversibly inhibits VAP-1 and MPO activity with equivalent and enhanced nanomolar potency, respectively, when compared to benchmark clinical VAP-1 and MPO inhibitors. SNT-8370 is selective, exhibiting >100-1000-fold more potency for VAP-1 and MPO versus other mammalian (per)oxidases and shows no significant off-target activity in established preclinical screening panels. In vivo, SNT-8370 is metabolically stable, exhibits a favourable pharmacokinetic/pharmacodynamic profile without CNS penetration, and effectively inhibits VAP-1 and MPO activities. Moreover, compared to monotherapy, SNT-8370 more effectively inhibits leukocyte infiltration in mouse peritonitis, carrageenan air pouch, and lipopolysaccharide-induced lung injury models of acute inflammation. SNT-8370 is also protective in preclinical models of myocardial ischemia-reperfusion injury and unilateral-ureteral-obstruction-induced nephropathy. Collectively, our results support SNT-8370 as a first-in-class, mechanism-based dual inhibitor of VAP-1 and MPO, and as a promising therapeutic for the clinical treatment of inflammatory disorders. The Author(s) 2025.
• Atrial Fibrillation Detected by Handheld ECG and Ischemic Stroke Risk in a 55- to 64-Year-Old Chinese Population
  Sun, Wen; Freedman, Ben; Martinez, Carlos; Wallenhorst, Christopher; Chan, Christy K.Y.; Yan, Bryan Ping Yen
  JACC: Asia (Vol. 5/11) – 2025
  Background Atrial fibrillation (AF) screening is recommended at age ?65 years, but the age threshold in Asians is uncertain because of higher ischemic stroke risk <65 years. Objectives This study evaluated AF screening yield in a Chinese population aged 55 to 64 years, comparing stroke risk of those with and without AF, and the effect of oral anticoagulants (OAC). Methods Patients aged 55 to 64 years attending Hong Kong outpatient clinics underwent opportunistic handheld electrocardiogram screening. Repeat screening was performed if >1 clinic visits. Crude incidence rate ratios of ischemic stroke were determined and compared between 3 cohorts: screen-detected AF; clinically diagnosed AF; and no AF. Ischemic stroke risk for all AF categories was compared with individuals without AF, using adjusted subdistribution HRs (aSHRs) accounting for death as a competing risk. Results Of 3,926 subjects screened, 338 (8.6%) had known AF, and 3,588 had no AF history. New AF yield was 0.8% (28/3,588). AF was clinically diagnosed during follow-up in 2.3% (n = 82) and during subsequent screening in 7 subjects. Of 35 subjects with screen-detected AF, 26 (74%) had ?1 non-age, non-sex risk factor for stroke, mean age 60.8 2.5 years, and mean CHA<inf>2</inf>DS<inf>2</inf>-VASc score 1.9 1.4. At a median follow-up of 5.0 years, 2 patients (6%) with screen-detected AF experienced ischemic stroke, both with ?1 non-age, non-sex risk factor. AF exposure without OAC treatment was associated with highest risk of ischemic stroke (aSHR: 3.4 [1.3-8.5]). OAC treatment had similar low ischemic stroke risk as no AF. Conclusions Although diagnostic yield of AF screening in Chinese patients aged 55 to 64 years is low, those with AF are at increased stroke risk and may warrant being on anticoagulation. 2025 The Authors.
• Endo-chip laser-induced thrombus formation: a vessel-on-chip model for in vitro testing of antithrombotic agents
  Dupuy, Alexander; Qi, Miao; Fenwick, Jemma C.L.; Yates, Daisie M.; Coleman, Paul R.; Gamble, Jennifer R.; Ju, Lining Arnold; Passam, Freda H.
  Blood Vessels, Thrombosis and Hemostasis (Vol. 2/4) – 2025
  Mouse models, such as the intravital laser-induced model of thrombus formation, are commonly used for mechanistic and preclinical studies in thrombosis. However, their translational value is limited by species differences. Few in vitro models incorporate laser-induced vascular injury. Here, we developed an endothelialized microfluidic device, the Endo-chip, to model thrombus formation in response to laser injury. Citrated blood was treated with IXA4, an endoplasmic reticulum stress inducer, or with antithrombotic agents including antitissue factor antibody (5G9), antiplatelet drugs (abciximab, aspirin), and anticoagulants (argatroban, heparin). Fluorescently labeled antibodies (to platelets, fibrin, or von Willebrand factor [VWF]), annexin V or the calcium dye Cal520, were added to the blood. After recalcification at 10 mM, blood was perfused through the Endo-chip at a shear rate of 100 s1 or 800 s1. Endothelial injury was induced with a 355-nm laser pulse producing a focal 10-?m injury, and phosphatidylserine exposure on endothelial cells within ?1 cell diameter from the injury site. Annexin V-positive endothelial cells expressed tissue factor and released VWF, supporting localized platelet and fibrin deposition. The thrombus formed a teardrop morphology aligned with flow incorporating VWF with increasing shear. IXA4 enhanced platelet cytoplasmic calcium. Platelet accumulation was inhibited by abciximab but not aspirin, whereas coagulation inhibitors (5G9, argatroban, heparin) markedly reduced thrombus formation. These findings support that the Endo-chip laser-injury model incorporates key features of thrombus formation after endothelial injury, and provides a humanized, in vitro, alternative or auxiliary to mouse models for preclinical studies and antithrombotic drug development. 2025 The American Society of Hematology
• Measuring early vascular aging in youth: an expert consensus document from the Youth Vascular Consortium
  Hersant, Jeanne; Kruger, Ruan; Bianchini, Elisabetta; Kigstein, Karsten; Sinha, Manish D.; Hidvi, Erzset Valia; Kodithuwakku, Vimarsha; Mill, JosGeraldo; Dz, Alejandro A.; Zocalo, Y.; Bia Santana, Daniel; Celermajer, David S.; Hanssen, Henner; Johansson, Madeleine; Pucci, Giacomo; Litwin, Mieczyslaw S.; Stone, Keeron J.; Pugh, Christopher J.A.; Stoner, Lee; Urbina, Elaine M.; Bruno, Rosa Maria; Nilsson, Peter M.; Climie, Rachel Emma D.
  Journal of Hypertension (Vol. 43/11) – 2025
  Since the conceptualization of early vascular aging (EVA) in 2008, significant efforts have been made to develop and improve its assessment. Initially lead by the investigation of arterial stiffness through pulse wave velocity (PWV), several additional vascular aging biomarkers have gained prominence in recent years. Despite expanding literature addressing methodological concerns associated with these biomarkers in youth, a standardized approach for clinical evaluation of EVA remains elusive, leaving pertinent gaps in understanding the optimal methodology. This article, resulting from international consensus efforts from the Youth Vascular Consortium, aims to provide an updated overview of methods available to measure EVA in youth and to discuss challenges in translating these methods into clinical practice. 2025 Wolters Kluwer Health, Inc. All rights reserved.
• Trends and cross-country inequities by region, sex, age in the mortality, incidence, and disability-adjusted life years of COVID-19: Analysis from the Global Burden of Disease Study 2021
  Xu, Xiaohan; Sun, Jing; Zhang, Jinlun; Yang, Zhou; Ou, Chunquan
  PLOS Neglected Tropical Diseases (Vol. 19/10) – 2025
  Background The coronavirus disease 2019 (COVID-19) pandemic has imposed a substantial disease burden globally and has further exacerbated pre-existing health inequities. This study aimed to provide a comprehensive assessment of the burden and inequities associated with COVID-19 across diverse populations. Methods Using data from the Global Burden of Disease 2021, we systematically analyzed deaths, incidence, disability-adjusted life years (DALYs), and years of life lost (YLLs) of COVID-19 stratified by sex, age, and region. The temporal trends pre-and post-2019 (i.e., 19902019 and 20192021) were measured using average annual percent change (AAPC). Additionally, the cross-country absolute and relative sociodemographic index (SDI)-related health inequities were assessed using the slope index and concentration index, respectively. The SDI is a composite development indicator that incorporates income, educational attainment, and fertility conditions. Results Trends in the global burden of all-cause mortality and DALYs exhibited significant declines (AAPC < 0) from 1990 to 2019 but underwent a marked reversal trend (AAPC > 0) following the COVID-19 pandemic. In 2021, COVID-19 resulted in 2.28 billion incident cases and 7.89 million deaths globally, with an age-standardized DALYs rate of 2,501 per 100,000 population. While incidence rates were relatively evenly distributed across populations, mortality was disproportionately higher among males and older adults. Substantial health inequities in the burden of COVID-19 were evident across 204 countries and territories, with absolute widening inequities notably in 2021 (e.g., the slope index of inequity for DALYs rose from 2,713 in 2020 to 4,044 in 2021). Greater inequities are disproportionately concentrated among males, middle-aged and older individuals, and regions with lower SDI levels. Conclusions These findings highlight the substantial disease burden of COVID-19 and elucidate the multidimensional health inequities exacerbated by the pandemic, providing crucial evidence for targeted interventions to address inequities and strengthen resilience in future global health emergencies. 2025 Xu et al.
• Heart Failure With Preserved Ejection Fraction in Patients With Obesity: A Growing Cardiometabolic Concern
  Sindone, Andrew Paul; Abhayaratna, Walter P.; Chan, Alicia; Leung, Melissa; Hopper, Ingrid K.; Amerena, John V.; de Pasqulae, Carmine G.; Burdeniuk, Christine Mary; Coats, Andrew J.S.; Atherton, John James
  Heart Lung and Circulation (Vol. 34/10) – 2025
  Heart failure (HF) affects approximately 2.1% of adult Australians and is associated with substantial morbidity and mortality. Approximately half of all patients with HF have HF with a preserved ejection fraction (HFpEF), which is increasing in incidence driven by an ageing population and an increasing prevalence of obesity and diabetes. Obesity drives HFpEF via multiple mechanisms, with a linear relationship between various anthropometric measures and the risk of developing HFpEF. Heightened diagnostic awareness is required to identify patients with obesity-associated HFpEF, given the availability of therapeutics that have been shown to improve quality of life and clinical outcomes, including sodium-glucose cotransporter 2 inhibitors, mineralocorticoid receptor antagonists, and glucagon-like peptide-1 agonist-based therapies. This review provides an overview of our current understanding of the impact of obesity on the development of HFpEF and outlines an approach to diagnosis and new therapeutic options. 2025
• The Effect of Body Size and Obesity on Cardiovascular Haemodynamics and Myocardial Mechanics
  Madronio, Christine M.; Pathan, Shahab K.; Low, Gary Kim Kuan; Nundlall, Nishant; Williams, Kathryn Helen; Badorrek, Sally; Devadas, Michael; Gallaty, Lynette; Madan, Kedar; Loh, Han; Ahmad, Shiva; Negishi, Kazuaki; Pathan, Faraz K.
  Heart Lung and Circulation (Vol. 34/10) – 2025
  Background: To improve management of cardiovascular-kidney-metabolic syndrome, a better understanding of the early effects of body size on the heart is crucial and remains under investigation, considering the increasing global prevalence of obesity. Most data available on cardiovascular haemodynamics come from echocardiography despite the known challenges in image acquisition in the context of overweight and obesity. Using cardiac magnetic resonance imaging, we aimed to further investigate the effect of body size on cardiac output (CO) and other early imaging biomarkers of cardiovascular disease. Method: Participants including healthy volunteers and individuals with obesity who were planning to undergo bariatric surgery were recruited from two completed studies. The participants underwent cardiac magnetic resonance imaging. Measures of cardiovascular haemodynamics and myocardial mechanics were collected, including CO, stroke volume, heart rate, chamber volumes, and myocardial strain. The relationship of these variables with body size were assessed. Results: A total of 57 participants were recruited (79% female; mean age, 41 years). A positive linear relationship was observed between CO vs body mass index (BMI) (p<0.01) and body surface area (BSA) (p<0.01). A similar trend was seen with stroke volume vs BSA (p<0.01) and BMI (p<0.01). Indexation to BSA rendered chamber volumes similar. We found significant differences in left and right atrial strain between the groups. Regression analysis demonstrated an association between left ventricular global longitudinal strain and right atrial strain with BSA and between left ventricular global longitudinal strain, right ventricular free wall strain, and right atrial strain with BMI. Conclusions: Obesity is associated with increased CO; this increase is a result of cardiac remodelling and consequent increase in stroke volume. Obesity is associated with an impairment of subclinical markers of cardiovascular disease measured using multichamber strain. 2025 The Authors
• A Scoping Review of Health-Related Citizen Science Projects Involving Indigenous Peoples in Australia and Internationally
  Chau, Josephine Yuk Yin; Hunter, John; Gwynn, Josephine Diana; Dharmayani, Ms Putu Novi Arfirsta; Henson, Connie; Ludlow, Briellyn; Skinner, John C.; Gwynne, Kylie G.; Rambaldini, Boe
  Health Promotion Journal of Australia (Vol. 36/4) – 2025
  Issue Addressed: Citizen science, an approach to health promotion that involves public participation and collaboration, has been posited as a promising approach to reach diverse or marginalised populations. This scoping review aims to explore the involvement of Aboriginal and Torres Strait Islanders and other First Nations and Indigenous peoples internationally in citizen science in health-related studies. While current health promotion in Indigenous communities is already strongly embedded in participatory approaches, we sought to examine whether citizen science methodologies have been used in health promotion and see what it could add. Methods: We searched three databases for self-identified citizen science studies on health-related topics in the peer-reviewed literature using the term citizen science combined with search terms relevant to Aboriginal and Torres Strait Islanders and global Indigenous populations. We recorded data about project characteristics and the citizen science approach used and appraised the cultural engagement quality of studies included. Results: Eleven articles were included for full-text review. Included studies focused on a range of health-related topics, including environmental issues, physical health, food security, and youth mental health. Six studies (55%) adopted a co-created citizen science approach in which citizen scientists had input in key project phases and activities as collaborators and partners. The remaining studies took contributory (27%) or collaborative (9%) approaches, while no studies were citizen-led. The cultural engagement quality of included citizen science projects was positive overall, although there were areas for improvement, specifically having clear Indigenous research leadership and governance, and transparent agreements on rights to cultural and intellectual property arising from the research. Conclusion: Citizen science projects focusing on health-related issues among Indigenous peoples and communities are relatively few. The potential of this approach to enrich current community-based participatory or co-design approaches to health promotion among Indigenous communities remains to be determined. So What?: Future citizen science projects involving Indigenous people and communities should prioritise and support Indigenous-led citizen science approaches where communities initiate, lead, and govern research processes. Cultural engagement quality could be improved, particularly in relation to having Indigenous-led research governance, and rights of access to and protections of Indigenous intellectual and cultural property. 2025 The Author(s). Health Promotion Journal of Australia published by John Wiley & Sons Australia, Ltd on behalf of Australian Health Promotion Association.
• The Role of Gut-Brain Tryptophan Metabolism and Fatty Acid Peroxidation in the Effect of Sleep Deprivation on Anxiety and Depression in PCOS Mice
  Han, Ting; Liu, Shangjing; Liu, Hao; Wang, Xin; Yang, Xiaojia; Chan, Shanan; Tumanov, Sergey; Cannon, Richard David; Yang, Yang; Ting-Li Han, Ting Li Han
  Molecular Neurobiology (Vol. 62/10) – 2025
  Polycystic ovary syndrome (PCOS) is the most prevalent endocrine disorder in women of childbearing age. Numerous studies have indicated a significantly elevated incidence of depression and anxiety in women affected by PCOS, often attributed to dysbiosis of gut microbiota resulting from poor sleep quality. However, the intricate relationship between sleep disorders, gut microbiota, and depression/anxiety in PCOS remains unclear. In this study, we aimed to elucidate the effects of sleep deprivation on the anxiety and depression of PCOS mice through an investigation of the gut-brain axis in order to understand the potential microbialhost interactions contributing to the occurrence of these psychological disorders. We found that sleep deprivation induced symptoms of depression and anxiety in PCOS mice and exacerbated PCOS-like pathology. Moreover, sleep deprivation altered the gut microbiota composition by suppressing beneficial bacteria such as Lactobacillus and Ruminococcus species. Additionally, sleep deprivation upregulated intestinal tryptophan-kynurenine metabolism, increased intestinal wall permeability, promoted systemic inflammation, and compromised blood-brain barrier integrity. Furthermore, the hippocampal metabolomic analysis indicated that sleep deprivation affected the metabolism of fatty acid and oxylipins, upregulated the tryptophan-kynurenine metabolic pathway, and exhibited a significant correlation with anxiety and depressive behaviors. Overall, this study suggests that sleep deprivation plays a pivotal role in the pathological mechanism of depression and anxiety in PCOS mice by modulating tryptophan and lipid metabolism through the gut-brain axis. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2025.
• Association of an impaired GH-IGF-I axis with cardiac wasting in patients with advanced cancer
  Frlich, Ann Kathrin; Porthun, Jan; Talha, Khawaja Muhammad; Lena, Alessia; Hadzibegovic, Sara; Wilkenshoff, Ursula M.; Sonntag, Frederike; Nikolski, Anja; Ramer, Luisa Valentina; Zeller, Tanja; Keller, Ulrich Bernd; Bullinger, Lars B.; Anker, Stefan D.; Haverkamp, Wilhelm L.; von Haehling, Stephan; Doehner, Wolfram; Rauch, Ursula; Skurk, Carsten; Cleland, John G.F.; Butler, Javed J.; Coats, Andrew J.S.; Landmesser, Ulf E.; Karakas, Mahir; Anker, Markus S.
  Clinical Research in Cardiology (Vol. 114/9) – 2025
  Background: Growth hormone (GH) resistance is characterized by high GH levels but low levels of insulin-like growth factor-I (IGF-I) and growth hormone binding protein (GHBP) and, for patients with chronic disease, is associated with the development of cachexia. Objectives: We investigated whether GH resistance is associated with changes in left ventricular (LV) mass (cardiac wasting) in patients with cancer. Methods: We measured plasma IGF-I, GH, and GHBP in 159 women and 148 men with cancer (83% stage III/IV). Patients were grouped by tertile of echocardiographic LVmass/height2 (women, < 50, 5061, > 61g/m2; men, < 60, 6074, > 74g/m2) and by presence of wasting syndrome with unintentional weight loss (BMI < 24kg/m2 and weight loss ? 5% in the prior 12months). Repeat echocardiograms were obtained usually within 36months for 85 patients. Results: Patients in the lowest LVmass/height2 tertile had higher plasma GH (median (IQR) for 1st, 2nd, and 3rd tertile women, 1.8 (0.94.2), 0.8 (0.22.2), 0.5 (0.31.6) ng/mL, p = 0.029; men, 2.1 (0.83.2), 0.6 (0.11.7), 0.7 (0.21.9) ng/mL, p = 0.003). Among women, lower LVmass was associated with higher plasma IGF-I (68 (48116), 72 (4895), 49 (3576) ng/mL, p = 0.007), whereas such association did not exist for men. Patients with lower LVmass had lower log IGF-I/GH ratio (women, 1.60 0.09, 2.02 0.09, 1.88 0.09, p = 0.004; men, 1.64 0.09, 2.14 0.11, 2.04 0.11, p = 0.002). GHBP was not associated with LVmass. Patients with wasting syndrome with unintentional weight loss had higher plasma GH and GHBP, lower log IGF-I/GH ratio, and similar IGF-I. Overall, GHBP correlated inversely with log IGF-I/GH ratio (women, r = ? 0.591, p < 0.001; men, r = ? 0.575, p < 0.001). Additionally, higher baseline IGF-I was associated with a decline in LVmass during follow-up (r = ? 0.318, p = 0.003). Conclusion: In advanced cancer, reduced LVmass is associated with increased plasma GH and reduced IGF-I/GH ratio, suggesting increasing GH resistance, especially for patients with wasting syndrome with unintentional weight loss. Higher baseline IGF-I was associatedwith a decrease in relative LVmass during follow-up. The Author(s) 2024.