International Journal of Translational Medicine

Background/Objectives: Anxiety and stress are interrelated and connected to reduced health-related quality of life. Botanicals such as Apocynum venetum L. (A. venetum) have been shown to improve health outcomes. No human studies have been conducted in a diverse large group of healthy adults in the US. The purpose of this randomized, double-blind, placebo-controlled study was to evaluate the effects of Venetron^® Rafuma (A. venetum leaf extract) on self-reported anxiety levels and overall health outcomes compared to placebo. Methods: Healthy adults (N = 476) seeking improvement in self-reported anxiety and stress were randomly assigned to receive 50 mg of A. venetum (n = 234) or placebo (n = 242) for 6 weeks. Feelings of anxiety were assessed at baseline and weekly using Patient-Reported Outcomes Measurement Information System (PROMIS™) Anxiety 8A. Perceived stress, sleep quality, and cognitive function were evaluated at baseline and weekly using validated assessments. A linear mixed-effects regression model was used to compare the change in health outcome scores between active and placebo groups. Results: A total of 370 participants completed at least one additional assessment and were included in the analysis: 179 in the active arm and 191 in the placebo arm. There was a significant difference between the groups in the rate of improvement in perceived stress and sleep disturbance. The active group was significantly more likely to experience a Minimal Clinically Important Difference (MCID) in their perceived stress and marginally significantly more likely to experience an MCID in their feelings of anxiety. Participants who reported experiencing side effects did not significantly differ between arms. Conclusions: Venetron^® may be safe and effective therapy for stress and sleep disturbance among those suffering from feelings of anxiety. Full article

Background/Objectives: Phosphate level is a critical factor in the health of dialysis patients, as it is linked to cardiovascular risk. In peritoneal dialysis (PD), phosphate removal is related to residual kidney function, dietary intervention, and the ability of the visceral peritoneum to transport phosphate. The role of dialysis prescriptions in phosphate management is not sufficiently enhanced. Standardizing a phosphate removal propensity marker could optimize the peritoneal dialytic program. Our preliminary report aims to evaluate a simple model of phosphate handling and to assess which marker during the peritoneal equilibration test (PET) could better describe the propensity of phosphate removal through the peritoneal membrane. Methods: We hypothesized a simple two-compartment model to describe phosphate removal driven by diffusion. We performed an explorer study on 10 PD patients to assess the reliability of the two-compartment model. In each patient, we evaluated the basal condition and performed a PET with 2 L of 3.86% glucose exchange to assess phosphate handling. We collected blood and peritoneal effluent samples at the beginning of the test (t0), after 1 h (t1), and after 4 h (t4). We proposed and examined the following biomarkers: the ratio between dialysis effluent phosphate and plasma at t4 (PHO-D/P4); the difference between dialysis effluent phosphate at t0 and t4 (PHOΔd0-d4); and phosphate permeability–area product at t4 (PHO-PxA4). Results: 9 men and one woman with a mean age of 58.7 ± 16.7 years and a mean dialysis vintage of 25 ± 18.3 months were enrolled. The PHO-D/P4 mean was 0.68 ± 0.18, the PHO-Δd0-d4 median was 0.89 mmol/L [0.7–1.19], and the PHO-PxA4 mean was 1.7 ± 0.85. PHO-D/P4was significantly related to creatinine D/P4 (beta 1.49, p < 0.001), PHO-Δd0-d4 was significantly influenced by plasma phosphate at t0 (beta 0.56, p < 0.001), and the PHO-PxA4 was significantly influenced by ultrafiltration (beta 0.003, p < 0.001). Conclusions: In our two-compartment model, we observed the independence of the PHO-D/P4marker, which could serve as a potential marker for standardizing phosphate handling. However, PHO-Δd0-d4 and PHO-PxA4 normalized by plasma phosphate at t0 and ultrafiltration rate were able to reserve a potential good performance as markers in phosphate handling standardization. Full article

Background/Aims: We explored the possibility of using urine polar metabolites as non-invasive biomarkers of alcohol-associated liver disease (ALD) for early-stage diagnosis and severity assessment, as well as the possible changes in metabolic pathways in ALD patients. Methods: Polar metabolites were extracted with 80% methanol, and parallel 2DLC-MS was used for polar metabolite quantification. Results: Data from untargeted metabolomics showed that 194 metabolites were significantly changed in patients, and three metabolites can differentiate healthy controls (HC), non-severe ALD, and severe alcohol-associated hepatitis (severe AH) with high accuracy (0.92–0.97). Pathway analysis showed that arginine biosynthesis and histidine metabolism pathways were among the pathways containing the metabolites that were most altered in the urine of patients. Metabolites in the urea cycle, histidine catabolism, and histidine dipeptides pathways were notably increased in the urine of ALD patients, but none of the metabolites in these two pathways can simultaneously differentiate patients from healthy volunteers and non-severe ALD from severe AH. As the top differentiated pathways, the alterations of arginine biosynthesis and histidine metabolism indicate their importance in the metabolic dysfunction of ALD. Conclusions: Our results show that the abundance changes of specific metabolites can differentiate the disease severity of ALD, showing the potential of urine polar metabolites as non-invasive biomarkers for early-stage diagnosis and disease severity assessment of ALD. Full article

Background/Objectives: Guided bone regeneration (GBR) is a regenerative technique used to treat maxillary osseous defects to enable implant placement for prosthetic rehabilitation. It is generally performed with the use of barrier membranes and bone substitute materials of human or animal origin. Here, we report the clinical and histological outcomes of a horizontal GBR, treated using only synthetic biomaterials. Methods: A graft of nanocrystalline hydroxyapatite (NH) embedded in a silica gel matrix was used to fill a horizontal bone defect. The graft was covered with a titanium-reinforced dense polytetrafluoroethylene (TR-dPTFE) membrane, and primary closure was completed and maintained for 10 months. Then, the site was re-opened for membrane removal and implant insertion. During implant bed preparation, a bone biopsy was obtained for histological evaluation. A metal–ceramic crown was fitted, and the 5-year follow-up after prosthetic loading showed clinical and radiographically healthy tissues. Results: Histological examination revealed good integration of the biomaterial into the surrounding tissues, which were composed of lamellar bone trabeculae and connective tissue. New bone formation occurred not only around the NH granules but even inside the porous amorphous particles. Conclusions: The combination of NH and the TR-dPTFE membrane produced good clinical and histological results, which remained stable for 5 years. Full article

Introduction: Dyslipidemia, characterized by abnormal blood lipid levels, is a key risk factor for cardiovascular disease. Socioeconomic status can play a role in the development of chronic disease, including as an influence on risk factors for chronic diseases such as cardiovascular disease. Methods: This study analyzes the relationship between socioeconomic status and dyslipidemia using a population-based cross-sectional survey (NHANES 2017–2020 data). A cohort of 5862 adults was examined, focusing on socioeconomic factors (income, education, occupation) and their association with lipid profiles while controlling for sociodemographic, lifestyle, and medical variables, contributing to understanding how health disparities may affect chronic disease outcomes. Results: Low socioeconomic status was consistently associated with higher dyslipidemia risk, while high socioeconomic status demonstrated a modest protective effect. Age, BMI, hypertension, and diabetes were key predictors, highlighting the need for targeted interventions. Conclusions: This study underscores the critical role of socioeconomic status in dyslipidemia risk. Low socioeconomic status consistently increased the odds of dyslipidemia. While high socioeconomic status demonstrated some protective effects, these were diminished when accounting for lifestyle and clinical factors, highlighting the complex interplay of socioeconomic status and health behaviors. Full article

Background: Active nasal surveillance culture (ANSC) is recognized to enable rapid detection of antibiotic-resistant bacteria in the intensive care unit (ICU), which can contribute to the prevention of Ventilator-associated pneumonia (VAP). This study aims to evaluate the usefulness of ANSC in assessing the development of VAP in ICU patients. Methods: Patients admitted to the Yamagata Prefectural Central Hospital ICU from January 2017 to 2018 (Term 1) or January 2020 to December 2021 (Term 2) and underwent invasive mechanical ventilation supports were eligible for this study. Nasal swab samples were collected from the patients upon their admission to the ICU. The diagnosis of VAP was made according to the criteria set by the Centers for Disease Control and Prevention. Results: A total of 467 patients (156 women) in term 1, and 312 patients (113 women) in term 2 were enrolled. The incidence of VAP in term 2 was higher than in term 1 (7.1% vs. 12.8%, respectively). ANSC isolated several causative pathogens from the patients on admission who later developed VAP. Haemophilus influenza, Streptococcus pneumoniae, Stenotrophomonas maltophilia, and Pseudomonas aeruginosa had a 100% match rate with the sputum culture, indicating a perfect relation between ANSC results and sputum culture in VAP (+) cases. Conclusions: The isolation of high-risk bacterial species by ANSC could foresee the development of VAP in ICU patients and efficiently prevent VAP in critically ill patients. Full article

Background/Objectives: Tumor cell migration depends on the actin cytoskeleton modified by actin-binding proteins (ABPs). Overexpression of cofilin or thymosin beta4 (Tß4) has been correlated with an increase or decrease in their migratory activity, respectively. Methods: Immunostaining of tumor cells and transfection with EGFP-tagged cofilin or bicistronic vectors leading to independent expression of EGFP and Tß4. Determination of cell migration by transwell or agarose drop assay. Results: We modulated by transfection the intracellular concentrations of cofilin and Tß4 of two colon (3LNLN and EB3) and one breast carcinoma (MDA-MB-231) cell line and analyzed their migratory activity. Increasing wild-type cofilin did not alter their migratory activity, whereas the constitutively active S3A–cofilin mutant elevated migration. Transfection leading to an up- or downregulation of Tß4 showed that MDA-MB-231 and 3LNLN cells responded with a decrease or increase in migration, respectively. Exposure of MDA-MB-231 and 3LNLN cells to increasing concentrations of extracellular Tβ4 (or His-tagged Tß4) induced a biphasic response of migration, being highest around 0.24 µM and decreased at higher extracellular Tß4. Immunostaining of 3LNLN cells exposed to 0.24 µM extracellular His-tagged Tß4 with anti-His antibody indicated its uptake co-localizing with integrin-linked kinase at cell attachment points. Furthermore, the exposure to 0.24 µM His-tagged Tß4 led to increased phosphorylation of AKT1/2 and secretion of matrix metalloproteases. These effects and tumor cell migration were abrogated after exposure of 3LNLN cells to 2.8 µM His-Tß4, also inducing apoptosis in a number of cells. Conclusions: Tumor cell migration can be inhibited by high extracellular Tß4. Full article

Background: Fabry disease (FD) results from pathogenic GLA variants, causing lysosomal α-galactosidase A (α-GalA) deficiency and sphingolipid ceramide trihexoside (Gb3 or THC) accumulation. Disease phenotype varies widely but cardiomyopathy is commonly life-limiting. As a multisystemic disorder, FD initiates at the cellular level; however, the mechanism/s underlying Gb3-induced cell dysfunction remains largely unknown. This study established an in vitro mutation-specific model of Fabry cardiomyopathy using human-induced pluripotent stem cell (iPSC)-derived cardiomyocytes to explore underlying cell pathology. Methods: Skin biopsies from consenting Fabry patients and normal control subjects were reprogrammed to iPSCs then differentiated into cardiomyocytes. The GLA mutations in Fabry cell lines were corrected using CRISP-Cas9. Phenotypic characteristics, α-Gal A activity, Gb3 accumulation, functional status, and lipid analysis were assessed. Cardiomyocytes derived from two patients with severe clinical phenotype and genotypes, GLA^c.851T>C, GLA^{c.1193_1196del}, and their respective corrected lines, GLA^{corr c.851T>C}, GLA^{corr c.1193_1196del}, were selected for further studies. Results: Cardiomyocytes derived from individuals with FD iPSCs exhibited stable expression of cardiomyocyte markers and spontaneous contraction, morphological features of FD, reduced α-Gal A activity, and accumulation of Gb3. Lipidomic profiling revealed differences in the Gb3 isoform profile between the control and FD patient iPSC-derived cardiomyocytes. Contraction strength was unchanged but relaxation after contraction was delayed, mimicking the diastolic dysfunction typical of Fabry cardiomyopathy. Conclusions: iPSC-derived cardiomyocytes provide a useful model to explore aspects of Fabry cardiomyopathy, including disruptions in sphingolipid pathways, proteomics, and multigene expression that together link genotype to phenotype. The platform potentially offers broad applicability across many genetic diseases and offers the prospect of testing and implementation of individualised therapies. Full article

Colorectal cancer (CRC) is the third most common cancer and a leading cause of cancer-related mortality worldwide, with prognosis significantly deteriorating at advanced stages. While current diagnostic methods, such as colonoscopy and tissue biopsy, are widely employed in clinical practice, they are invasive, expensive, and limited in assessing tumor heterogeneity and monitoring disease processes, including therapy response. Therefore, early and accurate detection, coupled with minimal invasion and cost-effective strategies, are critical for improving patient outcomes. Liquid biopsy has emerged as a promising, minimally invasive alternative, enabling the detection of tumor-derived components. This approach is increasingly utilized in clinical settings. The current key liquid biopsy modalities in CRC include circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), and RNA-based biomarkers such as long non-coding RNAs (lncRNAs), microRNAs(miRNAs), and circular RNAs (circRNAs), and tumor-educated platelets (TEPs). These methods provide valuable insights into genetic and epigenetic tumor alterations, and serve as indicators for early detection, treatment monitoring, and recurrence prediction. However, challenges such as assay standardization and variability in sensitivity persist. This review delves into the clinical applications of liquid biopsy in CRC management, highlighting the transformative roles of ctDNA, CTCs, and non-coding RNAs, TEPs in early detection, prognostic assessment, and personalized therapy. In addition, it addresses current limitations and explores potential advancements to facilitate their integration into routine clinical practice. Full article

Background and Objectives: Docosahexaenoic acid (DHA) has been shown to modulate various voltage-gated ion channels and both excitatory and inhibitory synapses. Nonetheless, its exact effect on nociceptive signaling in the trigeminal system has yet to be elucidated. The purpose of the current investigation was to assess if acute DHA given intravenously to rats diminished the excitability of wide dynamic range spinal trigeminal nucleus caudalis (SpVc) neurons in response to mechanical stimulation in vivo. Methods: Single-unit extracellular activity was recorded from SpVc neurons in response to mechanical stimulation of the whisker pad in anesthetized rats. Responses to both non-noxious and noxious mechanical stimuli were analyzed in the present study. Results: The mean firing frequency of SpVc wide dynamic range neurons in response to both non-noxious and noxious mechanical stimuli was significantly dose-dependently inhibited by DHA, and the effect was seen within 5 min. After approximately 20 min, the inhibiting effects dissipated. Conclusions: These results suggest that, in the absence of inflammatory or neuropathic pain, the acute intravenous administration of DHA reduces the activity of trigeminal sensory neurons, including those responsible for pain, indicating that DHA could be utilized as an adjunct and alternative therapeutic agent for managing trigeminal nociceptive pain, including hyperalgesia. Full article

Background/Objectives: Cancer-associated fibroblasts (CAFs), which are an important component of the tumor microenvironment, have been reported to have an adverse effect on conventional radiotherapy. This study aims to elucidate the effects of CAFs in boron neutron capture therapy (BNCT) using a three-dimensional (3D) oral cancer model. Methods: Three-dimensional cancer models were fabricated using patient-derived CAFs or patient-derived normal oral fibroblasts (NOFs) and a human oral squamous cell carcinoma cell line. Each 3D cancer model was performed with either a conventional X-ray treatment or BNCT and additionally analyzed histomorphologically. Results: The 3D oral cancer-CAFs model demonstrated a greater depth of cancer cell invasion than the 3D oral cancer-NOFs model. Radiation therapy for the 3D oral cancer models indicated a trend for decreasing cancer cell invasion and cell number with dose dependence in both X-ray and BNCT. In comparison with X-rays, BNCT showed a consistent increase in the number of NOFs and a significant reduction in the number of CAFs. Conclusions: BNCT for the 3D oral cancer model was shown to be effective against cancer cells and CAFs but not against NOFs, indicating its usefulness as a minimally invasive treatment for advanced cancer. Furthermore, it is indicated that the 3D oral cancer-CAFs model is a valuable tool to evaluate cancer treatment and research, particularly in high-grade malignant tumors with invasion. Full article

Background: Cystic Fibrosis is an inherited disorder caused by mutations in the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) gene, encoding a chloride and bicarbonate channel widely expressed in epithelia. Loss of CFTR function leads to dehydration of the epithelium surface with thicker mucus secretions from tissues. The lungs, pancreas, liver, intestines, and sweat glands are the most common affected organs. However, pulmonary disease remains the main cause of morbidity and mortality. Fortunately, elexacaftor/tezacaftor/ivacaftor (ETI) therapy is showing unprecedented clinical benefits in patients with Cystic Fibrosis (CF) carrying at least one F508del mutation in the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) gene. However, almost 35% of the CF population living in the Mediterranean area still lacks effective CFTR modulator therapies because of the elevated incidence of patients with (pw)CF harboring CFTR rare mutations (RMs), different from F508del. Methods: Twenty-three pwCF harboring RM including the N1303K underwent off-label ETI treatment for 6-12 months. Respiratory function in terms of FEV1 and FVC was measured after 3, 6, and 12 months of treatment. In addition, we analyzed sweat chloride concentration, body mass index (BMI), and quality of life before and after treatment. Possible adverse effects were recorded. Results: All patients included in this off-label program displayed a substantial improvement in respiratory function. In particular, patients carrying the N1303K mutation showed an improvement in FEV1 and FVC similar to that observed in subjects harboring the F508del mutation, although sweat chloride concentration was not significantly decreased. No severe adverse effect was reported. Conclusions: This study strengthens the clinical efficacy of ETI in pwCF harboring the N1303K and other CFTR rare variants. Since these CFTR RMs have not been approved for ETI therapy in Europe, this study may promote the inclusion of these variants in the list of CFTR mutations responsive to ETI. Full article

Background: The spontaneous rupture of the internal iliac artery (IIA) is an exceedingly rare vascular event, typically associated with congenital anomalies or degenerative conditions. This report details an unprecedented case of isolated IIA rupture in an elderly patient with evidence of plaque rupture but devoid of congenital vascular pathology. Case Presentation: An 81-year-old Caucasian male presented to the Emergency Department following a syncopal episode and acute right iliac fossa pain. His significant medical history was atrial fibrillation managed with anticoagulation (Apixaban), non-insulin-dependent diabetes mellitus, and recent hospitalization for multidrug-resistant Klebsiella pneumoniae pneumonia. Initial imaging with contrast-enhanced computed tomography revealed an aneurysmatic dilatation of the right IIA, indicative of rupture. An endovascular repair was performed, employing a combination of stent grafts to achieve proximal and distal sealing and to restore vascular continuity. Outcome: The patient exhibited hemodynamic stability throughout the perioperative period and was transferred to the general ward postoperatively. However, he suffered a recurrent rupture on the 30th postoperative day, prompting a second endovascular intervention to extend the graft landing zone into the common iliac artery. Intraoperative findings confirmed localized plaque rupture as the underlying trigger for the initial vessel rupture. He ultimately achieved clinical stability and was discharged on the 35th postoperative day. Discussion: This case illustrates the critical importance of recognizing spontaneous IIA rupture as a potential complication in elderly patients, particularly in the context of recent severe infections. While the relationship between the rupture and the Klebsiella pneumoniae infection remains speculative, this report underscores the necessity of further research into the role of infectious processes in vascular integrity and susceptibility to rupture. Conclusions: The successful management of this rare and complex vascular emergency using endovascular techniques underscores the evolving landscape of minimally invasive interventions. This case contributes to the limited existing literature on spontaneous IIA rupture and highlights the need for increased clinical vigilance regarding atypical presentations in similar patient populations. Full article

Background: Biomarkers have emerged as a cost-effective tool to risk stratify patients presenting to the emergency department with chest pain. The measurement of serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) and myeloperoxidase (MPO) may improve the identification of patients who are more likely to have abnormal stress test results and require revascularization. Methods: In this prospective observational study, we evaluated the use of NT-proBNP and MPO in predicting abnormal stress testing results and revascularization in patients presenting to the ED with chest pain and an intermediate TIMI risk score. The serum levels of NT-proBNP and MPO were obtained at enrollment. Stress testing or coronary angiography was performed at the discretion of the treating physician. Clinical outcomes were followed at index hospitalization, 6 months, and 1 year. Results: A total of 485 patients were enrolled. NT-proBNP had a fair ability to predict abnormal stress testing results (AUC 0.69, p < 0.001). Based on the Mann–Whitney U test, there was a detectable difference in the median serum levels of both biomarkers among patients who did not undergo revascularization compared to patients who did undergo revascularization (NT-proBNP 70.5 vs. 250, p < 0.001, MPO 341 vs. 471, p < 0.001). NT-proBNP and MPO revealed a meaningful ability to predict revascularization in all patients (NT-proBNP AUC = 0.725, p < 0.001, MPO AUC = 0.653 p < 0.001). Conclusion: Elevated serum NT-proBNP was a fair predictor of abnormal stress test results. Furthermore, higher serum NT-proBNP and MPO levels were associated with revascularization events up to 1-year follow-up and were found to be meaningful predictors of coronary revascularization. Full article

(1) Background/Objectives: This pilot study aims to address the research gap on the interplay between ocular and systemic parameters as well as sex hormones in men. (2) Methods: We measured intraocular pressure (IOP), central corneal thickness (CCT), and macular thickness (CMT) in nine healthy male volunteers. These measures, along with blood glucose; blood pressure; and sex steroid hormones (testosterone, estrogen, and progesterone), were measured twice for each subject. Linear regression was used to determine the individual effects of these measures as well as self-reported age, height, and weight. (3) Results: Height, weight, systolic blood pressure, blood glucose, and estrogen significantly predicted IOP and CMT. CCT models were more limited, with systolic blood pressure and estrogen as the most significant predictors. (4) Conclusions: Our findings suggest that height, weight, blood pressure, and estrogen levels have the most substantial impact on ocular measurements. Testosterone levels were strongly associated with systemic health markers, a common result in the literature. However, ours appears to be the first study demonstrating estrogen’s effects on ocular structure or physiology in men. As many of our comparisons were statistically underpowered, future research with larger populations is needed to confirm these relationships and elucidate underlying mechanisms. Full article

Metabolic dysfunction-associated steatohepatitis (MASH) is rapidly becoming a leading cause of hepatocellular carcinoma and end-stage liver transplantation. Characterized by hepatic steatosis, lobular inflammation, and hepatocyte ballooning, there is a dire need to develop therapeutic strategies to mitigate MASH alongside the subsequent fibrosis and cirrhosis. For years, therapeutic development for the treatment of MASH had been considered a graveyard, with various pharmacotherapies failing to achieve clinical efficacy. However, the recent Food and Drug Administration (FDA) approval of Madrigal Pharmaceuticals’ Resmetirom in the United States provides a positive step in the collective effort to eradicate MASH. Granted, with much about Resmetirom’s long-term efficacy and safety still to be determined and with the multi-factorial nature of MASH pathogenesis, continuing to evaluate alternative therapeutic options remains in the best interest of the field. Currently, therapeutics previously approved for other ailments, alongside novel therapeutics developed specifically for the treatment of MASH, are being evaluated in late-phase clinical trials. However, considering the complex nature of the disease and varying clinical outcomes to assess treatment efficacy, achieving regulatory approval as a MASH therapeutic continues to be a rigorous endeavor. In this review, we summarize notable therapeutics of various mechanistic backgrounds having achieved, or actively undergoing, late-phase clinical trials for the treatment of MASH and offer our perspectives on anti-MASH therapeutic development. Full article

The ATP-binding cassette (ABC) transporter superfamily, one of the largest membrane protein families, plays a crucial role in multidrug resistance (MDR) in cancer by mediating the efflux of various chemotherapeutic agents, thereby lowering their intracellular concentrations and diminishing therapeutic effectiveness. Beyond drug efflux, these transporters are also involved in vital biological processes, such as signal transduction in cancer. Over the past few decades, extensive structural and functional research has provided valuable insights into ABC transporters’ broad substrate specificity and transport mechanisms, leading to promising strategies for overcoming MDR. This review will provide a structural understanding of the interactions between ABC transporters and inhibitors to develop novel cancer therapeutics. Additionally, we focus on methods such as irradiation-based immune therapies, thermal therapies, nanomedicine, CRISPR-Cas, and natural therapies that can genetically modify ABC transporters to reduce their expression or reverse the drug efflux ability. Knowledge gained from these approaches can then be translated into the development of new cancer therapeutics that can combat chemotherapy resistance. Full article

Background: This study aimed to investigate the acute effects of wild ginseng extract (Panax ginseng C.A. Meyer) on exercise performance, cognitive function, and fatigue recovery. Methods: Twelve healthy male participants were randomly assigned to receive either wild ginseng extract (WG) or a placebo prior to exercise trials, utilizing a double-blind, placebo-controlled cross-over design. The exercise protocol included 30 min cycling exercises followed by a 10-mile time trial, during which muscular power, strength, endurance, cognitive function, and fatigue were assessed. Additionally, biomarkers such as glucose, interleukin-6 (IL-6), myoglobin, total antioxidant capacity (TAC), and cortisol were measured. Repeated measures ANOVAs were used to analyze the effects of acute WG intake on the dependent variables. Results: In the placebo condition, both peak and mean power levels significantly decreased over time (p = 0.039 and p = 0.028, respectively), whereas no such decline was observed in the WG condition (p > 0.05). Furthermore, average reaction time (ART) was significantly delayed over time in the placebo trial (p = 0.005), while ART remained stable in the WG trial (p = 0.051). A significant increase in TAC was observed across time in the WG trial (p = 0.036), but no change was found in the placebo trial (p = 0.326). Cortisol levels significantly decreased over time in the WG trial (p = 0.001), while no change was observed in the placebo trial (p = 0.141). No significant differences were found for other variables between the WG and placebo trials (p > 0.05). Conclusions: The acute supplementation with WG positively influenced exercise performance by maintaining muscular power, reducing reaction time delay, and enhancing antioxidant capacity and cortisol regulation. These findings suggest that WG may be a promising ergogenic aid for improving exercise performance and recovery. NCT06679725 (ClinicalTrials.gov). Full article