Search Results (2,055)

Coronary artery bypass grafting (CABG) utilizing cardiopulmonary bypass (CPB) remains a cornerstone of treatment for advanced multivessel coronary artery disease. During the ischemic period, myocardial cells become injured and increasingly depend on anaerobic metabolism. After reperfusion, exposure of blood components to artificial surfaces, combined with ischemia–reperfusion injury, surgical trauma, and gut translocation of endotoxins, triggers a complex systemic inflammatory response syndrome (SIRS). This inflammatory cascade involves a tightly regulated network of humoral cascades (complement, contact, coagulation, and fibrinolytic systems) and cellular effectors (neutrophils, monocytes, endothelial cells, and platelets). Molecular signaling pathways, notably Toll-like receptor 4 (TLR4) activation, nuclear factor kappa B (NF-κB) nuclear translocation, mitogen-activated protein kinase (MAPK) phosphorylation, and NLRP3 inflammasome assembly, drive a cytokine storm characterized by massive releases of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-8 (IL-8). These molecular events lead to endothelial barrier disruption, vasoplegic shock, acute lung injury, myocardial dysfunction, and acute kidney injury. This comprehensive narrative review provides a detailed synthesis of the cellular and molecular mechanisms underlying CPB-induced SIRS, highlights recent advances in neutrophil extracellular trap (NET) dynamics and microvascular injury, and evaluates contemporary pharmacological and bioengineering therapeutic strategies designed to mitigate postoperative organ dysfunction. Full article

Introduction: Inflammation is a central component of the biological processes involved in orthopedic interventions, whether performed for acute traumatic injuries or chronic non-traumatic conditions. Cytokines play major roles in modulating these responses; however, data describing cytokine activity in bone marrow, particularly during orthopedic procedures, remain limited. This study aimed to examine variations in cytokine levels in traumatic and non-traumatic orthopedic surgeries by analyzing simultaneous bone marrow and plasma samples. Methods: This single-center prospective observational study with exploratory objectives included skeletally mature patients undergoing urgent surgery for acute traumatic fractures or planned surgery for chronic non-traumatic degenerative orthopedic conditions. Bone-marrow and peripheral plasma samples were collected simultaneously intraoperatively. All samples were tested in duplicate for interleukin-8 (IL-8), interleukin-6 (IL-6), interleukin-10 (IL-10), interleukin-4 (IL-4), interleukin-1 receptor antagonist (IL-1RA), and tumor necrosis factor-α (TNF-α) using developmental ELISA kits. Cytokine levels were compared between traumatic and non-traumatic groups and between bone-marrow and plasma samples. Results: Nineteen participants were included, providing 19 bone-marrow samples and 15 plasma samples, with the number of available measurements varying among cytokines. Bone-marrow IL-10 was detected in three of five available traumatic samples and in none of the eight available non-traumatic samples (unadjusted p = 0.035; false-discovery-rate-adjusted q = 0.178). Plasma IL-1RA concentrations were higher in traumatic than in non-traumatic patients (median 2828.00 versus 1269.00 pg/mL; unadjusted p = 0.038; q = 0.178). Bone-marrow IL-8 also showed higher concentrations in traumatic patients and approached the unadjusted significance threshold (p = 0.053; q = 0.178). No comparison remained statistically significant after FDR correction. Discussion: Bone-marrow IL-10 detection and plasma IL-1RA concentrations showed nominal between-group differences that did not remain statistically significant after multiple-comparison adjustment. Although preliminary and hypothesis-generating, these observations identify potentially informative local and systemic cytokine patterns and highlight the value of further investigating bone-marrow cytokine responses in orthopedic trauma. Full article

Obesity-related chronic kidney disease (ob-CKD) is an increasingly prevalent condition whose pathogenesis extends beyond excess body mass to the metabolic dysfunction of visceral adipose tissue (VAT). This narrative review synthesizes the mechanistic, diagnostic, and therapeutic dimensions of the adiporenal axis: the bidirectional crosstalk between dysfunctional visceral fat and the kidney. From a pathophysiological perspective, VAT promotes renal injury through four converging pathways: hemodynamic overload via the renin–angiotensin–aldosterone system and sympathetic activation; adipokine imbalance (leptin excess/adiponectin deficiency); chronic inflammation mediated by tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6); and direct lipotoxicity from ectopic renal fat deposition. Because body mass index (BMI)fails to capture these pathogenic mechanisms, visceral adiposity-centered assessment (using waist circumference, the visceral adiposity index, and cross-sectional imaging) is essential for accurate risk stratification. The recently proposed ob-CKD classification (types 1–5) links disease stage to therapeutic strategy across the full CKD continuum. The therapeutic landscape now includes agents with combined weight-loss and nephroprotective properties: glucagon-like peptide-1 (GLP-1) receptor agonists (FLOW trial), dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 agonists (tirzepatide), sodium-glucose co-transporter 2 inhibitors (SGLT2i), and non-steroidal mineralocorticoid receptor antagonists (finerenone), alongside metabolic surgery for refractory cases. This review provides an integrative framework for shifting clinical practice from BMI-centric to visceral adiposity-driven approaches in the prevention and management of ob-CKD. Full article

Background/Objectives: Osteoarthritis (OA) is characterized by cartilage degeneration, extracellular matrix (ECM) disruption, inflammation, and impaired joint function. A standardized phytosterol-rich avocado/soybean unsaponifiable preparation (CHL) was examined in monosodium iodoacetate (MIA)-induced OA in Sprague–Dawley rats. Methods: Rats were orally administered low-, medium-, or high-dose CHL for 2 weeks before and 4 weeks after MIA induction. Results: CHL attenuated MIA-induced weight-bearing deficits and structural joint abnormalities. CHL also reduced cartilage degradation markers, including cartilage oligomeric matrix proteins and the C-terminal crosslinked telopeptide of type II collagen. CHL alleviated systemic inflammation by reducing serum interleukin-6, tumor necrosis factor-α, and prostaglandin E2 levels. Furthermore, CHL decreased the serum levels of matrix metalloproteinases (MMP)-1, MMP-2, MMP-9, and MMP-13, indicating reduced matrix-degrading responses. In joint cartilage tissues, CHL suppressed the mRNA expression of pro-inflammatory mediators and catabolic genes, such as Mmp1, Mmp3, and Mmp9. Additionally, CHL modulated cartilage anabolism and ECM-related markers by reducing collagen type I alpha 1 chain expression and enhancing SRY-box transcription factor 9, tissue inhibitor of metalloproteinase 1, and collagen type II alpha 1 chain expression. High-resolution liquid chromatography-mass spectrometry profiling of CHL revealed several tentatively identified compounds, such as (+)-discodermolide, epicoccamide, and brasilicardin C. Conclusions: Overall, these findings indicate that CHL may attenuate MIA-induced OA-associated functional impairment, structural alterations, inflammation, and cartilage matrix degradation, with medium doses showing the strongest protective effects. However, because CHL administration was initiated before OA induction, these findings primarily reflect preventive/protective effects and may not directly represent the therapeutic efficacy of CHL in established OA. Full article

Background: Adipose-derived stem cells (ADSCs) are readily harvestable, tumour-homing cells that have been engineered as vehicles for antitumour agents. TNF-related apoptosis-inducing ligand (TRAIL) selectively triggers apoptosis in many cancer cells through death receptors DR4/DR5, while sparing most healthy cells. To date, only human TRAIL has been studied in such delivery systems; a fully homologous rat model (rat TRAIL delivered by rat ADSC) has not been tested, despite being essential for future syngeneic in vivo studies. Methods: In this pilot, exploratory study, we lentivirally transduced rat ADSC (rADSC) to express myc-tagged rat TRAIL, characterized the expression of TRAIL-pathway components in rADSC and three rat mammary carcinoma cell lines (RBA, HH-16.cl.4, SHZ-88) at the mRNA and protein levels, and assessed the antitumour effect of rTRAIL-rADSC using recombinant TRAIL dose–response, supernatant transfer, direct co-culture, and nine-day insert co-culture assays. Results: rADSCs were successfully transduced and produced cell-associated rat TRAIL (66.2 pg per 50,000 cells versus 4.4–5.7 pg in controls; p < 0.05); this ELISA measures total cell-associated (intracellular plus membrane-anchored) TRAIL rather than soluble TRAIL. rADSC expressed markedly higher levels of the decoy molecule osteoprotegerin and of DR4/DR5 than the cancer cells. Two of three cancer lines (RBA, HH-16.cl.4) were susceptible to rat TRAIL, and rTRAIL-rADSC reduced their growth and increased the proportion of dead cells, with morphological features compatible with both apoptosis and necrosis, most markedly in HH-16.cl.4; the effect was separable from the empty-vector control in HH-16.cl.4 but not in RBA. Conclusions: In this pilot study, homologous rat TRAIL delivered by rADSC is feasible and increases cell death in TRAIL-susceptible rat mammary cancer cells, but the effect is moderate at most, contact-dependent, and in one of two susceptible lines not attributable to TRAIL itself. These findings define both the potential and the limitations of a fully translational rat model of TRAIL-based biologic brachytherapy and provide a foundation for future in vivo studies. Full article

Purpose: This study aimed to evaluate the effects of active transcranial direct current stimulation (tDCS) compared with sham stimulation on circulating brain-derived neurotrophic factor (BDNF), pain-related outcomes, working memory, and inflammatory and neuroplasticity biomarkers. Methods: PubMed/MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, and ClinicalTrials.gov were searched from inception to May 2026. Randomized and controlled clinical trials comparing active with sham tDCS in adults were included. The primary outcome was post-treatment BDNF concentration. Secondary outcomes included pain intensity, pain catastrophizing, pain-related disability and functional interference, working memory, and circulating inflammatory or neuroplasticity biomarkers. Risk of bias was assessed using the revised Cochrane risk-of-bias tool. Mean differences (MDs) with 95% confidence intervals (CIs) were pooled using random-effects models. Serum and plasma BDNF were analyzed separately. Results: Twenty-one studies were included in the systematic review, of which 15 contributed to at least one quantitative synthesis and 12 study comparisons contributed to the primary BDNF analyses. Active tDCS did not significantly affect serum BDNF (MD = −0.01 [−0.15, 0.13], p = 0.890) or plasma BDNF (MD = 0.02 [−0.25, 0.29], p = 0.870) compared with sham stimulation. In contrast, active tDCS was associated with lower pain intensity (MD = −1.79 [−2.34, −1.23], p < 0.00001). No statistically significant difference was observed in the PCS total score or in the helplessness, magnification, or rumination subscales, although the point estimates generally favored active tDCS. For pain-related disability and functional interference, active tDCS was associated with lower PCP:S total scores and lower emotional interference, whereas no significant differences were observed for interference with daily activities or pain frequency. No significant differences were observed for working memory, interleukins, tumor necrosis factor-alpha, glial cell line-derived neurotrophic factor, interleukin-18, or soluble tumor necrosis factor receptors. Substantial heterogeneity was present in several pain-related and inflammatory biomarker analyses. Conclusions: Active tDCS was not associated with consistent differences in circulating serum or plasma BDNF or in the assessed peripheral inflammatory and neuroplasticity biomarkers compared with sham stimulation; however, these null peripheral findings should not be interpreted as evidence of absent central neuroplastic effects, because circulating measures may not adequately capture localized or transient biological changes within the central nervous system. Active tDCS was associated with improvements in some pain-related outcomes; however, the limited number of studies, substantial heterogeneity, and low certainty of the available evidence preclude firm conclusions regarding its clinical effectiveness for pain management. Full article

From a molecular perspective, colorectal cancer is a heterogeneous disease in which microsatellite instability (MSI) phenotypes, mismatch repair (MMR) status, chromosomal instability, or mutations in BRAF, KRAS, NRAS, and TP53 can influence prognosis, hereditary cancer risk assessment, and therapeutic approaches. Conventional biomarker testing via immunohistochemistry, polymerase chain reaction, and next-generation sequencing remains the diagnostic standard, but it can be limited by cost, turnaround time, tissue consumption, and uneven access. This narrative review synthesizes 30 peer-reviewed studies, identified across major scientific databases, that evaluate artificial intelligence (AI) platforms designed to detect molecular alterations from routine hematoxylin and eosin-stained colorectal cancer tissue slides. The strongest and most reproducible evidence exists for MSI phenotypes and MMR status, for which weakly supervised, attention-based, transformer-based, foundation-model, and clinically oriented multiple-instance learning systems achieve high discriminatory performance and particularly high negative predictive values at screening thresholds. BRAF mutation status is moderately predictable, although often through morphology associated with microsatellite instability or the CpG island methylator phenotype (CIMP). In contrast, despite promising single-center results, the predictability of KRAS, NRAS, PIK3CA, and other point mutations remains less consistently generalizable. Interpretability analyses indicate that these algorithms rely on features such as tumor-infiltrating lymphocytes, plasma cells, mucinous and medullary differentiation, necrosis, stromal architecture, tumor heterogeneity, nuclear morphometry, and tumor purity. Current evidence supports the use of AI as a triage and enrichment tool rather than a replacement for validated molecular diagnostics. Ultimately, prospective validation, pre-analytical standardization, calibrated thresholds, regulatory oversight, and pathologist-centered workflow integration are essential for successful clinical translation. Full article

Objective: To determine whether systemic inflammation in peripheral artery disease is primarily associated with necrosis or a secondary response, we evaluated the association of tissue oxygenation (red blood cells), acute metabolic stress (admission glucose, albumin), systemic inflammation (C-reactive protein), and the red blood cell-to-albumin ratio. Materials and Methods: We retrospectively analyzed 375 patients undergoing endovascular interventions (58 with necrosis, 317 without). C-reactive protein-to-albumin and red blood cell-to-albumin ratios were calculated. Associations were assessed using parallel multivariate logistic regression models. Results: The necrosis group had significantly higher admission glucose and C-reactive protein-to-albumin ratio, but a lower red blood cell count and red blood cell-to-albumin ratio. In multivariate models of fundamental biomarkers, C-reactive protein lost independent significance; low red blood cells (Odds Ratio: 0.348, p = 0.0003) and elevated admission glucose (Odds Ratio: 1.008, p = 0.0018) were the strongest independently associated variables. In composite index models, the C-reactive protein-to-albumin ratio became a dominant associated factor, attenuating the red blood cell-to-albumin ratio’s statistical significance. Conclusions: Anemia and admission hyperglycemia are strong correlates of tissue necrosis. Systemic inflammation appears to act as a secondary consequence of ischemic injury but profoundly exacerbates tissue loss when combined with nutritional depletion. Comprehensive medical management, including anemia correction and metabolic optimization, is fundamental for limb salvage. Full article

Allergic asthma is characterized by Th2-driven airway inflammation. Indoleamine 2,3-dioxygenase (IDO) maintains immune tolerance, but its role in modulating the anti-inflammatory actions of Curcumin (CN) is unclear. This study investigated whether CN retains efficacy in a rat model of Ovalbumin (OVA)-induced airway inflammation under pharmacological IDO inhibition. Rats were sensitized and challenged with OVA and treated with methylprednisolone (MP, 15 mg/kg), CN (200 mg/kg), the IDO inhibitor 1-MT (70 mg/kg), or CN+1-MT. Assessments included systemic and pulmonary leukocyte profile, delayed-type hypersensitivity (DTH), OVA-specific IgE, bronchoalveolar lavage fluid (BALF) inflammatory cells and nitric oxide (NO) levels, lung wet/dry weight ratio, gene expression of tumor necrosis factor alpha (TNF-α), interleukin (IL)-4, IL-6, Cxcr2 and transcription factor Nfkb1 and lung histopathology. CN alone or combined with 1-MT normalized leukocyte counts, suppressed eosinophilic and neutrophilic infiltration, restored BALF NO levels, reduced DTH response and OVA-specific IgE, decreased pulmonary edema, and preserved pulmonary vascular integrity. CN significantly attenuated TNF-α, IL-4, IL-6, and Cxcr2 gene expression despite pharmacological IDO inhibition. Histopathology revealed reduced inflammatory infiltration and maintained alveolar structure. CN maintains anti-inflammatory, immunomodulatory and tissue-protective efficacy in allergic airway inflammation despite pharmacological IDO inhibition. These findings call for future research on CN as a potential adjunctive therapy method for inflammatory airway diseases. However, to elucidate the underlying processes, more research on IDO activity and downstream immunometabolic pathways is needed. Full article

Objectives: The objectives of this study were as follows: (1) statistical investigation of the association between systemic diseases and dental pulp condition; and (2) utilization of locally running large language models (LLMs) to handle a large number of dental charts written in natural languages, while protecting patients’ information. Methods: A total of 5820 endodontic charts, including healthy controls and patients with a history of cancer, HIV, type 1 diabetes mellitus (DM), and type 2 DM, were selected from 15,147 samples. Using a local LLM environment, the dental charts from each group were classified into six categories: normal pulp (NP); reversible pulpitis (RP); asymptomatic irreversible pulpitis (AIP); symptomatic irreversible pulpitis (SIP); pulp necrosis (PN); and “others”, including unclear diagnoses. The distributions of these diagnoses across groups were statistically analyzed. Results: The prompt for the local LLM was repeatedly refined by classifying 400 test cases, resulting in 97.0% agreement with the judgments of three human dentists. The refined prompt was then applied to classify 5820 charts, followed by statistical analyses. Using a generalized linear mixed-effects model (GLMM), the cancer-history group showed a significantly higher NP and a lower AIP proportion, whereas the type 2 DM group showed a significantly lower AIP and a higher SIP proportion. Conclusions: The findings in the cancer-history group could be attributable to a worsened oral environment in the patients and difficulties in diagnosing AIP. Meanwhile, the lower proportion of AIP and higher proportion of SIP in type 2 DM group may reflect pulpal inflammation associated with the disease. Additional attention may be warranted for caries’ prevention and treatment in patients with type 2 DM. Full article

MGN-3 (Biobran), a denatured hemicellulose compound derived from rice bran, possesses potent immunomodulatory and antitumor activity; however, its clinical application is constrained by non-specific tissue distribution, rapid systemic elimination, and poor cellular uptake. To overcome these pharmacological limitations, we engineered MGN-3-loaded lipid nanoparticles (MGN-3.LNPs) formulated with bioactive cinnamon and avocado oils to optimize targeted drug delivery against solid carcinoma. Mice bearing subcutaneous Ehrlich Ascites Carcinoma (EAC) solid tumors received free MGN-3, plain lipid nanoparticles (plain LNPs), or MGN-3.LNPs three times weekly from day 8 to day 26 post-inoculation. The administration of MGN-3.LNPs achieved superior tumor volume suppression (95.00%) compared to free MGN-3 (69.00%) and plain LNPs (63.00%) (p < 0.0001). Mechanistically, MGN-3.LNPs effectively inhibited cancer cell proliferation by suppressing Ki-67 expression while promoting expression shifts that strongly suggest the engagement of mitochondrial-mediated apoptotic signaling, including upregulation of tumor protein p53, Caspase-3, Caspase-9, poly(ADP-ribose) polymerase (PARP), and cytosolic cytochrome c (Cyt c), alongside an elevated Bax/Bcl-2 ratio and reduced 8-hydroxy-2′-deoxyguanosine (8-OHdG) levels. Flow cytometric analysis confirmed that MGN-3.LNPs induced marked G0/G1 cell cycle arrest and promoted sub-G1 apoptotic cell accumulation, which was corroborated by Annexin V/propidium iodide (Annexin V/PI) staining and semiquantitative histopathological evaluation. Furthermore, MGN-3.LNPs downregulated the gene expression of proinflammatory cytokines tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) while restoring redox homeostasis in tumor tissues. Overall, lipidic nanoencapsulation significantly enhances the therapeutic efficacy of MGN-3 against solid tumors through superior nanoscale tissue penetration, prolonged retention, and synergistic lipid–drug bioactivity. Full article

Cell-free DNA (cfDNA) fragments represent emerging biomarkers of major interest in the assessment of male fertility and the management of couples undergoing assisted reproductive technology (ART). Easy to quantify and present in most biological fluids, seminal cfDNA could reflect apoptosis and necrosis occurring within the male reproductive system. In this study, we compared cfDNA concentrations, measured by means of qPCR targeting the RNase P gene, in the seminal plasma of men with severe sperm quality abnormalities, including very severe asthenozoospermia (n = 25), total azoospermia (n = 25), very severe oligozoospermia (n = 25), and very severe teratozoospermia (n = 25), with those of normozoospermic controls (n = 25). Mean cfDNA concentrations were particularly elevated in men with azoospermia (5.47 ± 1.17 µg/mL) and very severe teratozoospermia (3.25 ± 1.21 µg/mL), compared with controls (1.96 ± 0.27 µg/mL). After adjustment for multiple testing, only azoospermia and very severe teratozoospermia remained significantly associated with increased cfDNA levels (Holm–Bonferroni adjusted p < 0.003), whereas the other phenotypes did not maintain statistical significance. These results suggest that seminal cfDNA is markedly increased in the most severe forms of spermatogenic impairment, potentially reflecting enhanced germ cell apoptosis or testicular cell involvement. Despite some limitations, including the modest sample size and single-center design, our observations support the value of cfDNA as a promising non-invasive biomarker of sperm quality. Larger multicenter and longitudinal studies are needed to validate its clinical relevance and determine standardized reference thresholds for clinical application. Full article

Background: Hypervirulent Klebsiella pneumoniae (K. pneumoniae) easily causes bacteremia and liver abscess, and invades the eye via blood circulation to trigger blinding endogenous endophthalmitis. Widespread multidrug resistance limits antibiotic treatment, while traditional capsular polysaccharide vaccines cannot provide cross-serotype protection. Methods: We established a mouse model of intraperitoneal infection-induced endogenous endophthalmitis. BALB/c mice received two intramuscular injections of LNP-encapsulated PstS-YidR fusion mRNA vaccine, followed by challenge with hypervirulent K1 or K2 strains. We monitored body weight, quantified multi-tissue bacterial loads, detected IL-1β, IL-6 and TNF-α, and performed slit-lamp observation and liver/ocular histopathology. Results: The vaccine relieved systemic symptoms and weight loss, suppressed bacterial dissemination across peritoneal, blood, liver, lung and eye tissues, and reduced excessive inflammatory factor release. It alleviated intraocular suppurative lesions, preserved ocular structure, and mitigated liver abscess and hepatocellular necrosis, with equal protective efficacy against K1 and K2 and favorable in vivo safety. Conclusions: The PstS-YidR fusion mRNA vaccine blocks systemic spread and intraocular invasion of hypervirulent K. pneumoniae and alleviates multi-organ inflammatory damage. It serves as a safe candidate vaccine for preventing K1/K2-type hypervirulent Klebsiella infections and endogenous endophthalmitis. Full article

Accumulating evidence indicates that acute, life-threatening acetaminophen (APAP) poisoning is associated with systemic inflammation (SI). Investigating SI in experimental models holds promise for the development of pathogenetic therapies. This study aimed to evaluate SI manifestations in a murine model of APAP-induced toxic liver injury. Ten-week-old male C57Bl/6 mice received a single intraperitoneal dose of 600 mg/kg APAP, corresponding to the median lethal dose (LD50). To assess signs of multiorgan damage and SI, we performed histological examinations of internal organs as well as immunoenzymatic, hematological, and biochemical analyses of blood samples. Histological analysis revealed tissue alterations in the liver, kidneys, spleen, lungs, and heart, accompanied by functional impairment. Statistically significant changes were observed in plasma levels of tumor necrosis factor-α (TNF-α), IL-1α, IL-6, IL-10, C-reactive protein (CRP), platelet count, total bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine, and troponin I. Severe liver damage induced by APAP was associated with a cytokine storm, coagulopathy (thrombocytopenia), systemic alterations, pulmonary edema, and multiorgan dysfunction. Collectively, these findings indicate that severe APAP-induced liver damage triggers SI as a characteristic pathological process. Full article

(1) Background: Hybrid injectable biomaterials incorporating poly-D,L-lactic acid (PDLLA) and hyaluronic acid (HA) have emerged as an important class of biostimulators in aesthetic medicine, combining immediate soft-tissue augmentation with sustained collagen biostimulation. Although inadvertent intravascular injection is uncommon, it may lead to severe vascular complications. However, experimental data on the intravascular behaviour of PDLLA-HA hybrid biostimulators remain limited. This study evaluated vascular flow changes, countercurrent flow, and tissue response following intra-arterial injection of Juvelook^® and Juvelook Volume^® (VAIM Co., Ltd., Seoul, Republic of Korea) in a rabbit ear model. (2) Methods: A total of 112 rabbits (56 animals per product) were studied using an identical protocol. Each rabbit received bilateral intra-arterial injections of either 0.1 or 0.2 mL of PDLLA-HA hybrid biostimulator prepared at the manufacturer’s recommended 6 mL reconstitution or at serial dilutions ranging from 12 to 42 mL. Immediate vascular flow, countercurrent flow, macroscopic skin changes, and histopathological findings were evaluated over a 7-day observation period. (3) Results: At an injection volume of 0.1 mL, both products dispersed throughout the arterial system without persistent vascular occlusion or tissue necrosis. At 0.2 mL, transient vascular occlusion occurred in the standard (6 mL) and 12 mL dilution groups, with spontaneous restoration of blood flow within 5 min. Countercurrent flow was observed only in the Juvelook Volume^® (VAIM Co., Ltd.) cohort under these conditions. No skin necrosis, intravascular thrombosis, or embolisation was observed. Histopathological examination demonstrated preserved vascular integrity, with only focal perivascular foreign-body reactions consistent with injectable biomaterials. (4) Conclusions: Neither biostimulator caused persistent vascular occlusion or clinically significant tissue injury under the experimental conditions investigated. Injection volume and dilution influenced transient vascular flow disturbance and countercurrent behaviour. These findings provide experimental evidence that improves current understanding of the short-term intravascular behaviour of PDLLA-HA hybrid biostimulators and may contribute to future assessments of vascular safety. Full article