{"title":"Abstracts From the 51st Annual Meeting of Japanese Society for Microcirculation","authors":"","doi":"10.1111/micc.70088","DOIUrl":"10.1111/micc.70088","url":null,"abstract":"","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"33 7","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149137250","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yiyang Huang, Reshmi Patel, Aleksander S. Popel, Akanksha Bhargava, Arvind P. Pathak
{"title":"Empirically Informed Blood Vessel Network Reconstruction for Multimodality Image-Based Vascular Systems Biology","authors":"Yiyang Huang, Reshmi Patel, Aleksander S. Popel, Akanksha Bhargava, Arvind P. Pathak","doi":"10.1111/micc.70086","DOIUrl":"10.1111/micc.70086","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Reconstruction of vascular topology from imperfect 3D imaging data is essential for accurate hemodynamic simulations. Therefore, we developed a “gap-filling” method predicated on vascular biology and empirical patterns to restore incomplete vessels, independent of the imaging modality and spatial resolution employed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Our gap-filling algorithm reconstructs a vascular network based on distributions of its extant morphological features and employs different rules for healthy and tumor tissue. Algorithm performance was evaluated on (i) incomplete synthetic vascular trees with simulated CT noise, (ii) micro-CT-acquired brain tumor vasculature, (iii) micro-MRI-derived vasculature from a healthy mouse brain, and (iv) vasculature from the murine hippocampus imaged with light-sheet microscopy (LSM).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>For synthetic vascular trees, our algorithm restored more gaps when the volume fraction was between 80% and 95%. Peak vessel segment recovery occurred for intermediate volume fractions (86%–89%). Gap-filling performance was impacted when image noise was introduced. Across CT, MRI, and LSM, our method successfully reconnected missing vessel segments while preserving the overall features of the vascular network. Gap-filling of tumor vasculature, with its abnormal topology, was better when tumor-specific reconstruction rules were employed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our method showed efficient restoration of vascular network connectivity for 3D data derived from common imaging modalities at different resolutions. We also demonstrated the significance of applying distinct biologically-informed rules when reconstructing healthy and tumor vascular networks.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"33 7","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149137214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nikhil Kumar, Ryan Homes, Halley Ravuri, Mark Midwinter
{"title":"The Association Between Sublingual Microvascular Dysfunction and Plasminogen Activator Inhibitor-One Levels in Chronic Kidney Disease Patients: An Exploratory Study","authors":"Nikhil Kumar, Ryan Homes, Halley Ravuri, Mark Midwinter","doi":"10.1111/micc.70089","DOIUrl":"10.1111/micc.70089","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Explore potential associations between sublingual microcirculatory measures and plasma plasminogen activator inhibitor-one concentrations in patients attending the kidney transplant assessment clinic and healthy controls.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A single-center cohort study was performed by retrospectively recruiting 44 kidney transplant assessment clinic attendees and 15 nested non-renal failure controls who were selected from a larger pool (<i>N</i> = 44). The nested controls were frequency matched to the kidney transplant assessment clinic cohort by sex, ethnicity and diabetes. Sidestream dark field videomicroscopy (MicroScan, Microvision Medical, Amsterdam) of the sublingual microcirculation allowed quantification of five microcirculatory parameters in all patients: total vessel density, microvascular flow index, portion of perfused vessels, heterogeneity index and perfused vessel density. Plasma plasminogen activator inhibitor-one concentrations were determined using sandwich ELISA. Median (IQR) were reported for non-normally distributed data. Mann–Whitney-Wilcoxon tests were performed to compare the distribution of ranks between non-normally distributed groups (<i>U</i>-statistic) with <i>p</i> < 0.05 considered statistically significant. The Benjamini–Hochberg adjustment was applied to nominal <i>p</i>-values (<i>q</i>-value) to account for inflation of the false discovery rate across multiple exploratory analyses, with <i>q</i> < 0.05 considered statistically significant.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Plasminogen activator inhibitor-one levels were significantly higher in controls than those attending the transplant clinic (18.0 (11.5), 10.2 (6.8) ng/mL; U = 158, <i>p</i> = 0.006). Among kidney transplant patients, nominal associations revealed PAI-1 was inversely correlated with hemodynamic parameters perfused vessel density (<i>p</i> = 0.04, <i>r</i> = −0.32) and microvascular flow index (<i>p</i> = 0.01, <i>r</i> = −0.38); neither survived the Benjamini–Hochberg adjustment (<i>q</i> = 0.24 and <i>q</i> = 0.12, respectively). No other correlations between PAI-1 and any of the sublingual microcirculatory measures survived the Benjamini–Hochberg adjustment in both cohorts.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>PAI-1 is potentially associated with maladaptive hemodynamic changes in the sublingual microcirculation, implying its dysregulation may potentiate microvascular dysfunction. The results, however, must be interpreted with caution as no associa","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"33 7","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/micc.70089","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149137447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sophia Mavris, Rachel Chin, Shao-Yun Hsu, Rudolph L. Gleason, J. Brandon Dixon, Zhanna Nepiyushchikh
{"title":"Effect of Sex, Anesthesia Method, Physiological Asymmetry, and Strain on Rat Lymphatic Vessel Contractility Assessed via Near-Infrared Spectroscopy and Linear Mixed-Effects Modeling","authors":"Sophia Mavris, Rachel Chin, Shao-Yun Hsu, Rudolph L. Gleason, J. Brandon Dixon, Zhanna Nepiyushchikh","doi":"10.1111/micc.70087","DOIUrl":"https://doi.org/10.1111/micc.70087","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study aims to investigate the effect of sex, anesthesia administration method, lymphatic physiological asymmetry, and strain on popliteal lymphatic collecting vessel contractile function and transport in effort to create a research comparison standard for experimentations using rat popliteal lymphatics.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Naïve female and male (8–10 weeks old) Sprague–Dawley and Lewis rats (both left and right hind limbs) under two forms of anesthesia administration (ketathesia/dexdomitor and isoflurane) were used to assess lymphatic contractility and transport function via near-infrared imaging and linear mixed-effects modeling.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We quantified lymphatic contractility and transport through five functional metrics (packet frequency, packet amplitude, normalized packet transport, packet width, and normalized packet integral) via near-infrared imaging and found that both sex and anesthesia method significantly affect pumping behavior, while physiological asymmetry had minimal influence. Additionally, we identified strain-dependent differences in contractile dynamics between Sprague Dawley and Lewis rats. Linear mixed-effects modeling further supported these results, highlighting the significant and differential roles that sex, anesthesia method, and strain play in modulating lymphatic contractile function.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our results showcase that to create standard comparison criteria for rat popliteal lymphatic models, one consistent method of anesthesia is essential and for sex to be considered as a biological variable. These findings underscore the physiological variability that must be accounted for when modeling lymphatic function and disease.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"33 7","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/micc.70087","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148943050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Adela Lewandowska, Dominika Sawicka, Aleksandra Jóźwiak, Agata Jędrzejewska, Alicja Braczko, Marzena Romanowska-Kocejko, Marta Żarczyńska-Buchowiecka, Barbara Kutryb-Zając, Marcin Hellmann, Paulina Mierzejewska
{"title":"Microvascular Dysfunction and Redox Imbalance in Long COVID","authors":"Adela Lewandowska, Dominika Sawicka, Aleksandra Jóźwiak, Agata Jędrzejewska, Alicja Braczko, Marzena Romanowska-Kocejko, Marta Żarczyńska-Buchowiecka, Barbara Kutryb-Zając, Marcin Hellmann, Paulina Mierzejewska","doi":"10.1111/micc.70085","DOIUrl":"10.1111/micc.70085","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Endothelial and microvascular dysfunction are key features of Long COVID. Disturbances in cellular redox balance, reflected by altered nicotinamide adenine dinucleotide (NAD<sup>+</sup>/NADH) dynamics, may underlie vascular impairment. Flow-Mediated Skin Fluorescence (FMSF) evaluates microvascular function by monitoring NADH fluorescence during ischemia and reperfusion. We integrated FMSF-derived microvascular phenotyping with targeted NAD<sup>+</sup> metabolite profiling to determine whether altered NAD<sup>+</sup> metabolism is associated with impaired microvascular responses in Long COVID.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Microvascular function was assessed in 36 patients with Long COVID and 47 age-matched controls using FMSF. NADH fluorescence changes during ischemia and hyperemia were analyzed as markers of endothelial responsiveness. NAD<sup>+</sup> and related metabolites were measured using high-performance liquid chromatography and mass spectrometry.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Patients with Long COVID showed impaired FMSF parameters, including blunted ischemic responses and delayed recovery after hyperemia, indicating microvascular dysfunction. These changes were accompanied by a reduced NAD<sup>+</sup>/NADH ratio and lower NADP levels, consistent with redox imbalance. Abnormal fluorescence profiles were associated with altered NAD<sup>+</sup> metabolism, including reduced precursor availability and accumulation of degradation products. Higher NR concentrations showed associations with selected microvascular and eNOS-related parameters.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>FMSF provides a clinically applicable tool for detecting microvascular dysfunction in Long COVID. NAD<sup>+</sup> redox imbalance is linked to impaired microcirculatory responses, supporting FMSF as a functional marker of microvascular impairment associated with altered NAD<sup>+</sup> metabolism.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"33 7","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148912803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A Data-Efficient Computational Framework for Reconstruction and Simulation of Microcirculatory Perfusion","authors":"Peilun Li, Xiang Geng, Yanfei Shen, Molei Yan, Qing Pan, Gangmin Ning","doi":"10.1111/micc.70084","DOIUrl":"10.1111/micc.70084","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Purpose</h3>\u0000 \u0000 <p>Microcirculation is essential for maintaining tissue viability and organ function by delivering oxygen and nutrients. Impaired microvascular perfusion may result in tissue dysfunction despite apparently normal macrocirculatory parameters. However, comprehensive experimental characterization of entire microvascular networks remains technically challenging, limiting quantitative assessment of network-level perfusion. This study aimed to develop a data-efficient computational framework for reconstructing microcirculatory network structure and estimating blood perfusion from sparse local vascular measurements.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Rat mesenteric microvascular networks, which share selected quasi-two-dimensional structural characteristics with human sublingual microcirculation, were used for methodological validation. Morphological and flow information was extracted from individual vessel segments, and three datasets, each containing 10 randomly selected venous bifurcations, were used to emulate limited data availability. A conditional generative adversarial network (cGAN) was pretrained on a larger source corpus and fine-tuned using each sparse target dataset. Venous trees were subsequently generated and integrated with derived arterial trees and capillary connections to reconstruct complete microvascular networks. Initial flow rates were assigned from local measurements, followed by network optimization using a structural adaptation model.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Five microcirculatory networks were generated for each sparse bifurcation dataset, enabling quantification of network-level perfusion descriptors, including blood-flow fractal dimension, multifractal spectrum, and capillary-flow heterogeneity. Under controlled distribution shift at the bifurcation-generation level, fine-tuning successfully shifted the distributions of generated bifurcation exponent and asymmetry ratio toward the corresponding sparse target data. The reconstructed networks exhibited broadly similar diameter-conditioned velocity and pressure trends to those in the reference network. Structural adaptation further differentiated the diameter–flow relationships in arterial and venous, with the fitted slopes approaching the corresponding reference values.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The proposed framework provides a data-efficient framework for physiologically plausible reconstruction of microcirculatory networks and estimation of network-level perfusion from sparse local bifurcation data. Validation in rat mesenteric microvascular networks demonstrates the met","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"33 7","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148865604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Overview of Endomucin in Vascular Homeostasis and Disease","authors":"Rui-Fan Yang, Xiao-Rong Wang, Jing Wang, Hui-Bo Du, Zhen-Ao Zhao, Zi-Gang Zhao","doi":"10.1111/micc.70083","DOIUrl":"https://doi.org/10.1111/micc.70083","url":null,"abstract":"<div>\u0000 \u0000 <p>Endomucin (EMCN), a highly glycosylated type I transmembrane sialomucin, is predominantly expressed on the luminal surface of venous and capillary endothelial cells and serves as a critical guardian of vascular homeostasis and immunological silencing. Its highly extended, O-glycosylated extracellular domain provides significant steric hindrance and electrostatic repulsion, functioning as a dual physical barrier that prevents nonspecific leukocyte tethering and adhesion. Beyond its anti-adhesive role, EMCN is a pivotal orchestrator of angiogenesis, modulating the vascular endothelial growth factor signaling cascade by facilitating vascular endothelial growth factor receptor 2 autophosphorylation at the Y1175 residue and subsequent receptor internalization. Furthermore, EMCN has emerged as a specialized marker for type H vessels and human hematopoietic stem cells, playing indispensable roles in vessel-bone coupling and hematopoietic development. Clinical evidence indicates that the dysregulation of EMCN expression or post-translational modifications contributes to the pathogenesis of diabetic complications, atherosclerosis, bone metabolic disorders, and tumor metastasis. This review systematically summarizes structural characteristics, expression patterns, and multifaceted biological functions of EMCN, providing a theoretical foundation for the development of novel therapeutic strategies for microvascular and metabolic diseases.</p>\u0000 </div>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"33 7","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148849119","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"eNOS Uncoupling, Shear-Stress Tolerance, and the Two-Threshold Model of Post-Exertional Malaise in Long COVID: A Mechanistic Hypothesis With Implications for Physiotherapy and Recovery Protocols","authors":"Yiannis K. Karipidis, Konstantinos Y. Karipidis","doi":"10.1111/micc.70082","DOIUrl":"10.1111/micc.70082","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To propose and make testable a mechanistic hypothesis for post-exertional malaise (PEM) in a clinically distinct subset of Long COVID patients, in whom delayed exertional symptoms coexist with consistently normal macrovascular investigations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Established vascular-biology literature is synthesized into an integrated, falsifiable model centered on endothelial nitric oxide synthase (eNOS) uncoupling, from which mechanism-specific predictions and a dynamic pre-/post-exertion biomarker validation framework are derived.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We propose that SARS-CoV-2-induced endotheliitis activates inducible nitric oxide synthase and silently depletes the tetrahydrobiopterin (BH4) pool on return to activity, shear-stress activation of structurally intact eNOS against a depleted BH4 background yields superoxide rather than nitric oxide, generating peroxynitrite that sustains a self-amplifying nitro-oxidative cycle. The Two-Threshold Model distinguishes a PEM threshold from a shear-stress-tolerance threshold and predicts that prolonged immobility may paradoxically erode endothelial function. eNOS uncoupling is positioned as one node among alternative microvascular pathways, and autonomic findings are proposed to be secondary within this phenotype.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This phenotype-specific, falsifiable hypothesis yields mechanism-derived predictions and rehabilitation implications consistent with symptom-contingent pacing guidance; it does not claim to explain all Long COVID presentations.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"33 6","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13506209/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148819039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Huan Li, Fan-Kai Chen, An-Qing Li, Ding-Zhou Weng, Chun-Shui Pan, Li Yan, Kai Sun, Jian Liu, Jing-Yan Han
{"title":"DangGuiSiNi Decoction and QiShenYiQi Pills Ameliorate Hyperpermeability and Edema Induced by Cold Exposure","authors":"Huan Li, Fan-Kai Chen, An-Qing Li, Ding-Zhou Weng, Chun-Shui Pan, Li Yan, Kai Sun, Jian Liu, Jing-Yan Han","doi":"10.1111/micc.70081","DOIUrl":"10.1111/micc.70081","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Limb frostbite caused by cold exposure is a prevalent injury in winter. However, effective therapies remain limited, particularly for cold-induced edema. This study evaluated the therapeutic potential of DangGuiSiNi Decoction (DSD), QiShenYiQi Pills (QSYQ), and their combination in a rat model of cold-induced limb injury.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Male Sprague–Dawley rats (180–220 g) were subjected to hind limb frostbite through 5-min dry ice exposure. Animals were administered with DSD, QSYQ, or their combination via oral gavage either 2 h pre-exposure or 5 min post-exposure, followed by daily dosing for 7 days. Hennepin Score, hind limb blood flow, FITC-albumin extravasation, rhodamine 6G-labeled leukocyte adhesion, expression of tight/adhesion junction proteins and basement membrane components, transient receptor potential (TRP) channel proteins, ATP content, and norepinephrine levels at 2 h, 24 h, and 7 days post-exposure were assessed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The combination of DSD and QSYQ significantly alleviated frostbite-induced edema and gangrene. Compared with control group, cold exposure increased the expression of TRPA1, TRPM8, RhoA, ROCK, p-MLC, adrenergic receptor α2c and norepinephrine content, while decreased the expression of tight and adherent junction proteins claudin-5, ZO-1, JAM-1, basement membrane proteins laminin and collagen-IV, ATP content, and the activity of mitochondrial complex I, II, IV and V. DSD primarily counteracted the cold-sensing and vasoconstrictive pathways by reducing TRPA1/TRPM8 expression, norepinephrine levels, and RhoA/ROCK activation, thereby improving blood flow. In contrast, QSYQ enhanced vascular barrier integrity by upregulating junction and basement membrane proteins, and boosted energy supply by increasing ATP content and mitochondrial complex activities. The combination of DSD and QSYQ produced aggregated therapeutic effects.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>DSD attenuates frostbite by inhibiting temperature-sensing and vasoconstrictive pathways to ameliorate ischemia, whereas QSYQ protects vascular barrier function and mitigates edema by restoring energy metabolism. Their combination exhibits complementary and synergistic effects, supporting its use as a promising adjunctive therapy for cold-induced injury.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"33 6","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148819022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Josi Gallo, Allison Miller, Emily Chan, Grace Chen, Luke Benner, Erik Sillaste, Brhandom Brisueno Lopez, Carolyn Bakx, Bohyun Ro, Juan Orsi, Lara Soares de Araujo, Ernesto Ramirez, Eloisa Herrera Ospina, Qifan Song, Daniel M. Hirai, Igor A. Fernandes, Bruno T. Roseguini
{"title":"Plantar Foot Microvascular Reactivity and Oxygenation in Type 2 Diabetes and Peripheral Artery Disease: An Exploratory Study","authors":"Josi Gallo, Allison Miller, Emily Chan, Grace Chen, Luke Benner, Erik Sillaste, Brhandom Brisueno Lopez, Carolyn Bakx, Bohyun Ro, Juan Orsi, Lara Soares de Araujo, Ernesto Ramirez, Eloisa Herrera Ospina, Qifan Song, Daniel M. Hirai, Igor A. Fernandes, Bruno T. Roseguini","doi":"10.1111/micc.70078","DOIUrl":"10.1111/micc.70078","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Microvascular dysfunction contributes to foot complications in type 2 diabetes (T2D) and peripheral artery disease (PAD), yet has been characterized primarily in non-plantar regions. We evaluated microvascular reactivity and oxygenation at ulcer-prone plantar sites and responses to combined heat therapy and intermittent pneumatic compression (HT + IPC).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Forty adults ≥ 50 years (Control <i>n</i> = 20, T2D <i>n</i> = 11, PAD with or without T2D <i>n</i> = 9) were studied. Plantar hallux CVC (laser Doppler flux/MAP) and forefoot StO<sub>2</sub> (near-infrared spectroscopy) were measured during local heating and reactive hyperemia. Responses to 60-min HT + IPC were evaluated using the contralateral foot as a control.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>At the plantar hallux, the increase in %CVCmax from baseline to the initial peak was attenuated in PAD compared with controls and T2D (<i>p</i> < 0.01), whereas plateau responses were similar. At the forefoot, PAD showed faster deoxygenation during ischemia and slower reoxygenation during reactive hyperemia (<i>p</i> < 0.01). During HT + IPC, popliteal blood flow increased similarly across groups; however, plantar StO<sub>2</sub> increased in controls and T2D but remained below baseline in PAD (<i>p</i> < 0.001).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These preliminary findings indicate impaired plantar microvascular function in a heterogeneous PAD cohort, most of whom also had T2D. Larger studies are needed to confirm these findings and to elucidate the underlying mechanisms.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"33 6","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/micc.70078","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148605087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}