Search Results (290)

Background/Objectives: Acute inflammatory episodes demand rapid symptom control while limiting systemic exposure. We assessed whether co-therapy with the selective cyclooxygenase-2 (COX-2) inhibitor etoricoxib and the corticosteroid betamethasone provides antinociceptive and anti-edema activity in a rat model with complete Freund’s adjuvant-induced arthritis (AIA). Methods: Male Wistar rats (n = 10/group) were allocated to seven groups: Intact, AIA disease control, indomethacin 5 mg/kg, etoricoxib 8 mg/kg, betamethasone 0.022 mg/kg, low-dose combination (4 + 0.011 mg/kg), and full-dose combination (8 + 0.022 mg/kg), administered orally once daily from Days 4 to 28. Paw edema, von Frey withdrawal thresholds, and clinical arthritis score were assessed longitudinally as area under the curve (AUC) values. Terminal joint tissues were profiled for cytokines, prostaglandin pathway mediators, and immune cell markers. Results: Both combinations reduced edema and improved mechanical thresholds. The full-dose combination exceeded either monotherapy regarding mechanical sensitivity and the arthritis index, consistent with additive activity. The low-dose combination matched full-dose monotherapies, consistent with a dose-reduction effect. Biomarker shifts indicated attenuated prostaglandin signaling and a pro-resolving cytokine balance. Conclusions: These findings support the further evaluation of etoricoxib–betamethasone co-therapy for acute inflammatory conditions. Full article

Background: Skeletal muscle (SM) plays a critical role in movement, metabolism, and organ protection, with its maintenance and regeneration relying on muscle satellite (stem) cells (MSCs). Prostaglandin E2 (PGE2) regulates MSCs, but PGE2 levels decline with aging due to increased catabolism by 15-hydroxyprostaglandin dehydrogenase (15PGDH), a negative regulator of muscle repair. Methods: This study aimed to employ artificial intelligence and machine learning (ML)-assisted, structure-based screening approaches to identify novel 15PGDH inhibitors. Supervised models (support vector machine, random forest, and XGBoost were trained on curated bioactivity data (IC₅₀ values) from the ChEMBL database and used to virtually screen the Maybridge compound library (~51,000 compounds). Results: The area under the curve (AUC) values of the developed models SVM, RF, and XGBoost were 0.96, 0.99, and 1.00, respectively. Promising inhibitors were further validated using structure-based virtual screening (docking), molecular dynamics simulations (200 ns), and MM-PBSA/GBSA analyses. The top five inhibitors (PD00616, HTS11491, HTS02629, AW00889, and HTS11190) were identified as active (ML analysis) and potential 15PGDH inhibitors based on their subsequent binding affinities, involvement of catalytic residues (Ser138, Tyr151, and Lys155), and complex stability. Additionally, these inhibitors were found to follow the drug-likeness criteria. Conclusions: These findings offer valuable insights for the development of novel therapeutics targeting 15PGDH to combat muscle degeneration and related pathologies, including aging and sarcopenia. Full article

Biomarker, the short form of “biological marker”, appeared in the scientific literature in the 1940s. Since then, many different definitions have been suggested, but a generally applicable explanation of the term biomarker in science is extremely challenging. The word biomarker is found in 1.3 million articles in the scientific database PubMed^® that currently comprises more than 39 million citations for biomedical literature. Biomarkers are closely associated with human health and disease. The present article attempts to approach and evaluate the multifaceted term “biomarker” from a clinical perspective by searching the PubMed database. The search term biomarker was combined with other search terms related to medicine, physiology, biochemistry, and chemistry. Currently generally accepted clinical biomarkers, such as the high-molecular-mass N-terminal prohormone of brain natriuretic peptide (NT-proBNP, 60%), prostate-specific antigen (PSA, 67%), and troponin (37%), serve as a kind of positive control. The combination of the search term biomarker with selected low-molecular substances of clinically non-validated and hence rather experimental character yielded surprisingly high fractions of 41% for 8-iso-prostaglandin F_2α, 39% for symmetric dimethylarginine (SDMA), and 28% for asymmetric dimethylarginine (ADMA). The results of our survey are presented and discussed in detail for a wide spectrum of diseases. We focused on mechanisms that are assumed to underlie the biological activity and specificity of biomarkers. We also considered potential roles of the analytical chemistry of biomarkers including the emerging metabolomics and proteomics. Reliable analytical methods have been used for the quantification of the isomeric low-molecular-mass ADMA and SDMA in human biological samples. ADMA, but not SDMA, is considered an endogenous inhibitor of the endothelium-derived nitric oxide (NO) synthesis, one of the most potent endogenous vasodilators. Paradoxically, the utility of ADMA and SDMA as biomarkers in the renal and cardiovascular systems seems to contradict their main biological activity. This prominent pair is representative of many biomarkers and reveals that the supposed biomarker utility is likely to be predicated on not yet considered biological activity. The majority of human diseases are heterogenic, affect many organs and seem to include different and overlapping biochemical pathways. In recent years, especially proteomic studies provided a series of new potential candidate biomarkers. However, such biomarkers must still be validated in the clinic before they can be introduced into clinical practice. This is perhaps the most critical phase in the discovery of disease biomarkers. Our analysis reveals that the area of biomarker research is highly challenging. With minor exceptions, there is no specific biomarker for a single disease. In addition to clinical examinations, a combination of several biomarkers seems to be needed for reliable diagnosis and therapy. Analytical chemistry, especially proteomics, delivers a huge amount of data, which may complicate and even hinder progress in this area. Specific quantitative analysis of candidate biomarkers observed by proteomics (and metabolomics) is highly recommended to proceed with the same biological samples from studies in which the biomarkers were discovered. Full article

Non-steroidal anti-inflammatory drugs (NSAIDs) are widely prescribed worldwide for their analgesic, antipyretic, and anti-inflammatory properties. However, their long-term use is associated with substantial gastrointestinal (GI) toxicity. Although upper GI injury has traditionally received greater attention, NSAID-induced enteropathy is now increasingly recognized as a common yet underdiagnosed condition. Advances in small-bowel imaging, particularly capsule endoscopy, have demonstrated that mucosal injury of the small intestine occurs in up to 70–80% of chronic NSAID users and may also develop after short-term exposure in otherwise healthy individuals, often without overt clinical symptoms. When symptoms do occur, NSAID-induced enteropathy is characterized by non-specific clinical manifestations and may lead to severe complications in approximately 1% of cases. The pathogenesis of NSAID-induced enteropathy is multifactorial and more complex than that underlying upper GI damage. It involves prostaglandin depletion, increased intestinal permeability, bile acid-mediated toxicity, enterohepatic recirculation of NSAIDs, and, importantly, interactions with the gut microbiota. Concomitant therapies, particularly proton pump inhibitors, may further aggravate small-bowel injury by promoting intestinal dysbiosis. Growing evidence supports a relevant contributory role for the gut microbiota as both a mediator and a modulator of NSAID-induced toxicity, affecting epithelial barrier function, oxidative stress, immune responses, and bile acid metabolism. This review provides an overview of current knowledge of NSAID-induced enteropathy, with a particular emphasis on the microbiota-driven mechanisms underlying mucosal injury. By integrating emerging microbiota-targeted therapeutic approaches, we propose a management algorithm that may help modify disease progression in a condition that remains frequently overlooked in clinical practice. Full article

Background/Objectives: Chronic inflammation is a key factor in the development and progression of colorectal cancer (CRC). When COX-2 levels and PGE₂ production increase, nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin (ASA) and selective COX-2 inhibitors, such as celecoxib and rofecoxib, are commonly employed. This paper presents the effect of anti-inflammatory drugs, primarilyNSAIDs, on the incidence of CRC. Methods: A comprehensive literature search (119 articles) was conducted with databases such as PubMed. During our research, we used keywords such as colorectal cancer (CRC), nonsteroidal anti-inflammatory drugs (NSAIDs), ASA, COX, precision oncology, and personalized medicine. Results: The development of CRC is primarily associated with chronic inflammation and the actions of COX-2 and prostaglandin E2 (PGE₂), which promote cancer cell proliferation and angiogenesis. Anti-inflammatory drugs act by inhibiting the secretion of COX-1 and COX-2 enzymes, which leads to reduced PGE₂ production and may limit tumor growth. Aspirin has the best-documented and studied anti-cancer effect; long-term use is associated with a reduced risk of CRC development and mortality through its anti-inflammatory and antiplatelet effects, thereby limiting metastasis. Particularly beneficial effects are observed in patients with mutations in the PIK3CA gene. Factors influencing the effectiveness of CRC treatment include molecular differences and tumor location. Conclusions: The future of CRC treatment and prevention lies in personalized medicine, which accounts for each patient’s genetic profile. Decisions regarding NSAIDs use and CRC prevention should consider the potential benefits and risks of side effects. Full article

Background/Objectives: The aim of this study was to investigate the effects of intraocular pressure (IOP)-lowering drops on the sublayers of the human tear film as assessed by a novel nanometer-resolution Tear Film Imager (TFI, AdOM, Israel). Methods: In a prospective, cross-sectional study, 98 eyes from 56 adult human subjects were imaged using the TFI. The dataset included data from 18 eyes from 12 subjects treated with preserved IOP-lowering drops and 80 eyes from 44 control subjects not under ocular hypotensive therapy. Subjects in the IOP treatment group used a variety of IOP-lowering medications, including prostaglandin analogs, beta-blockers, carbonic anhydrase inhibitors, alpha agonists, and combination drops. A linear mixed effects model was used to assess the association between IOP-lowering therapy and tear film (TF) metrics, controlling for age and intra-individual correlation. The following parameters were measured: muco-aqueous layer thickness (MALT), muco-aqueous layer thinning rate (MALTR), lipid layer thickness (LLT), lipid map uniformity (LMU), inter-blink intervals (IBI), and lipid break-up time (LBUT). Results: Average ages significantly differed (p = 0.013) between the treatment group (66.5 years) and control group (average age 51.5 years), and thus results were adjusted for age accordingly. IOP was 17.1 mmHg in the treatment group and 16.1 mmHg in the control group. When analyzing the sublayers of the TF, MALTR had a significant association with IOP-lowering therapy after adjusting for age, with a difference of −52.68 nm/s; 95% confidence interval [−96.87, −8.48]; p-value = 0.020. Additionally, IBI was significantly associated with IOP-lowering therapy after log transformation (p = 0.049), with shorter IBI in the treatment group. All other metrics (MALT, LLT, LMU, and LBUT) were statistically insignificant (p > 0.05). Conclusions: These pilot results suggest that IOP-lowering drops may accelerate thinning of the TF, specifically the muco-aqueous layer. Longitudinal studies with significantly larger samples are needed to specify the differential impact of various ocular hypotensive therapies on the human TF and the clinical implications of these findings. Full article

Background/Objectives: The ACE2/Ang-(1–7)/Mas receptor axis is a protective, counter-regulatory component of the RAAS that opposes Ang II/AT₁R-mediated vasoconstriction. The present study evaluated the pharmacological effects of Ang-(1–7) in the rat inferior vena cava (IVC), a venous capacitance vessel involved in the regulation of venous return and cardiac preload. We hypothesized that Ang-(1–7) exerts anti-contractile effects in the rat inferior vena cava through activation of potassium channel-dependent mechanisms in venous smooth muscle. Methods: Isolated IVC rings from Wistar rats were studied using organ bath assays. Ang-(1–7) effects were assessed on pre-constriction induced by angiotensin II (Ang II), phenylephrine (PE), endothelin-1 (ET-1), and thromboxane A₂ analog (U46619). Responses were recorded and quantified. Mechanistic involvement of nitric oxide (NO), prostaglandins, soluble guanylate cyclase (sGC), and K⁺ channels was evaluated using specific pharmacological inhibitors. Results: Ang-(1–7) attenuated Ang II-induced contraction. The effect was markedly reduced by tetraethylammonium (TEA), indicating a predominant role of potassium channel-dependent mechanisms in venous smooth muscle. In contrast, inhibition of nitric oxide synthase, soluble guanylate cyclase, or cyclooxygenase had minimal influence. Ang-(1–7) also produced concentration-dependent relaxation in PE-, ET-1-, and U46619-precontracted vessels, demonstrating agonist-dependent anti-contractile activity. Conclusions: Ang-(1–7) exerts significant anti-contractile effects in the rat inferior vena cava primarily through activation of TEA-sensitive K⁺ channels in venous smooth muscle. These findings demonstrate functional activity of the ACE2/Ang-(1–7)/Mas axis in a major venous capacitance vessel and provide mechanistic insight into Ang-(1–7)-mediated modulation of venous tone, supporting further investigation in in vivo models. Full article

Cross-reactivity among nonsteroidal anti-inflammatory drugs (NSAIDs) creates a significant clinical difficulty, especially in patients with NSAID hypersensitivity. These reactions are based on cyclooxygenase-1 (COX-1) inhibition and non-immunoglobulin E (IgE)-mediated reactions. COX-1 inhibition leads to dysregulation of arachidonic acid metabolism, with decreased prostaglandin synthesis and increased leukotriene production. Clinically, cross-intolerant reactions manifest in different phenotypes, including NSAID-exacerbated respiratory disease (NERD), NSAID-induced urticaria/angioedema (NIUA), and NSAID-exacerbated cutaneous disease (NECD). In contrast, true allergic reactions—such as single-NSAID-induced urticaria/angioedema and anaphylaxis (SNIUAA) and single-NSAID-induced delayed hypersensitivity reactions (SNIDHR)—are immunologically mediated and drug-specific. These phenotypes differ in underlying conditions, clinical manifestations, and patterns of NSAID tolerance. Paracetamol is generally considered a safer alternative due to its weak COX-1 inhibition; however, reactions may still occur, particularly at higher doses. Selective COX-2 inhibitors are usually better tolerated, however their safety should be confirmed, preferably through controlled drug provocation testing due to sporadic reactions in cross-intolerant patients. Understanding the distinction between pharmacologically mediated cross-intolerance and true allergic reactions is essential for accurate diagnosis, risk stratification, and therapeutic decision-making. This review summarizes current evidence on the mechanisms underlying NSAID hypersensitivity, analyzes the tolerability of paracetamol and alternative analgesics, and discusses practical management strategies to reduce the risk of adverse reactions. Full article

Conventional treatments for androgenetic alopecia (AGA) are often limited by suboptimal efficacy and potential adverse effects, highlighting the need for alternative approaches. We aimed to evaluate the efficacy and safety of a multi-targeted cosmetic formulation containing TrinogeniX™, composed of synthetic small-molecule inhibitors of glycogen phosphorylase, the prostaglandin D₂ receptor, and 15-hydroxyprostaglandin dehydrogenase, developed using the artificial intelligence-driven platform DeepZema^®, in individuals with AGA. This 24-week, randomized, double-blind, placebo-controlled trial involved 56 participants, of whom 49 completed the study. Efficacy was assessed using phototrichogram analysis, visual evaluation by dermatologists, and subjective questionnaires. Safety was evaluated based on adverse event reports and dermatological examinations. The test group demonstrated a significant increase in hair density and thickness over 24 weeks (p < 0.05), whereas no significant changes were observed in the placebo group. Expert visual assessments confirmed greater improvements in the test group. Subjective evaluations revealed consistently greater perceived improvements in hair loss symptoms, hair richness, and front hairline conditions in the test group. No adverse events or clinically significant abnormalities were observed. The multi-targeted cosmetic formulation (Motifull hair tonic) significantly improved hair density, thickness, and overall hair condition without adverse effects, suggesting its potential as a safe and effective option for AGA. Clinical trial registration: CRIS No. KCT0010804: A double-blind, randomized, placebo-controlled clinical trial evaluating the efficacy and safety of “Motifull Hair Tonic” (tentative name) for the alleviation of hair loss symptoms. Full article

Osteosarcoma is a highly aggressive canine bone tumor characterized by early metastasis and resistance to chemotherapy. Vasculogenic mimicry (VM), the ability of tumor cells to form microvascular channels independent of endothelial cells, can contribute to tumor progression and poor prognosis. In this in vitro study, we evaluated the effects of celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, on the canine osteosarcoma cell line D17. Celecoxib treatment significantly inhibited cell proliferation in a dose- and time-dependent manner, induced S-phase cell cycle arrest, and promoted apoptosis. Furthermore, celecoxib effectively disrupted VM formation on Matrigel. Transcriptome analysis revealed that celecoxib downregulated genes associated with angiogenesis and the COX pathway, notably PTGS2. Consistent with this, celecoxib treatment reduced the secretion of prostaglandin E2 (PGE2) in a dose-dependent manner. Crucially, the addition of exogenous PGE2 restored VM formation in celecoxib-treated cells, confirming that celecoxib-mediated VM suppression is dependent on the reduction of PGE2 levels. These findings establish the COX-2/PGE2 signaling axis as a key regulator of VM in D17 canine osteosarcoma cells and that celecoxib warrants further preclinical evaluation as a strategy to target both tumor growth and alternative vascularization. Full article

Background: Unfractionated heparin (UFH) remains the standard anticoagulant for extracorporeal membrane oxygenation (ECMO), despite complications, such as heparin resistance, heparin-induced thrombocytopenia, bleeding and variable pharmacokinetics. This has prompted the search for alternative and novel anticoagulation strategies, including pharmacologic agents, circuit modifications, and monitoring approaches. This scoping review aimed to map the breadth and characteristics of evidence on ECMO anticoagulation strategies beyond UFH. Methods: A comprehensive search of peer-reviewed and gray literature was conducted across PubMed, Cochrane, Clinical Trials, WHO Trials Registry, and conference abstracts through manual searches in key journals. Clinical, pre-clinical, and gray literature studies evaluating pharmacologic agents, anticoagulation-free or heparin-sparing, biocompatible circuits, and monitoring innovations were included. Data were charted and synthesized descriptively to identify trends, gaps, and emerging directions. Results: A total of 269 records were included. Evidence was highly heterogeneous among study designs, populations, ECMO modalities, and outcome definitions. Most clinical studies were retrospective cohorts and adult-centered, with limited multicenter randomized controlled trials and underrepresentation of neonatal and pediatric populations. Direct thrombin inhibitors were frequently studied and clinically implemented alternatives to UFH. Other agents, including nafamostat mesylate, prostaglandin E1, and factor pathway inhibitors remain early in clinical investigation. Anticoagulation-free strategies and biocompatible circuit technologies were mostly supported through pre-clinical and single-center studies. Monitoring and modeling innovations, like TEG, ROTEM, real-time imaging, and machine learning, are quickly emerging. Conclusions: ECMO anticoagulation is transitioning from UFH reliance toward diversified and personalized strategies. Future research should prioritize multicenter randomized controlled trials, standardize protocols, expand to neonatal and pediatric investigation, and integrate strategies. Full article

This review presents an innovative and timely exploration of how cytoprotection can serve as a cohesive therapeutic approach by which to address the hemorrhage–thrombosis paradox. Presenting counteraction of both hemorrhage and thrombosis as phase-dependent outcomes of vascular dysregulation, the manuscript synthesizes conceptual, experimental, and clinical evidence into a unified systems-level model focused on the stable gastric pentadecapeptide BPC 157, which acts as a cytoprotective mediator. In rodents, BPC 157 can simultaneously counteract hemorrhage and thrombosis without directly affecting the coagulation cascade (aggregometry, thromboelastometry). This cytoprotective framework (decreased hemorrhage, decreased thrombosis) stands with presentation of both hemorrhage and thrombosis in the wound, arrhythmias, and Virchow triad, and resolution of these disturbances. As proof of the concept (full cytoprotective effect), a vasoprotective cytoprotective mediator capable of bidirectional regulation, BPC 157, is effective for wound healing, arrhythmia control, and normalization of Virchow’s triad (i.e., following major injuries, occlusion/occlusion-like syndromes). As a comparison from a cytoprotective (partial vs. full) standpoint, conventional agents—anticoagulants, antiplatelet drugs, and fibrinolytics—provide only partial protection by targeting isolated components of hemostasis. Beta blockers, calcium channel blockers, prostaglandins, NO modulators, ACE inhibitors, and statins each exert broader cytoprotective effects; however, these actions remain incomplete and context-dependent, typically unidirectional, dose-limited, or are achieved at the expense of opposing pathological risks. Contrarily, for BPC 157, decreased hemorrhage (including both anticoagulants and antiplatelet agents), decreased thrombosis, effective wound healing, arrhythmia control, and normalization of Virchow’s triad involve preservation of endothelial integrity, normalization of microcirculation, modulation of the NO system, stabilization of hemostatic balance, and recruitment of adaptive collateral pathways. Nevertheless, reliance on preclinical models necessitates further clinical validation. Full article

The arachidonic acid pathway plays a pivotal role in the biosynthesis of important inflammatory and signal transducing agents such as prostaglandins, leukotrienes and thromboxanes. When this pathway is deregulated, it leads to pathological conditions such as cardiovascular diseases, metabolic diseases, and cancer. Two key enzymes of the pathway are cyclooxygenases (COXs) and lipoxygenases (LOXs), which are responsible for the production of prostaglandins and leukotrienes, respectively. Consequently, these enzymes have long been recognized as key therapeutic targets for the treatment and management of inflammatory disorders and other pathological conditions associated with inflammation. In this review, we describe the new evidence over the last 4 years regarding the arachidonic acid pathway. Moreover, we will pay attention to the structure and function of the COX-2 and 5-LOX enzymes and their role in inflammation, as well as define their active sites. Later, we will discuss the most potent, dual inhibitors of COX-2 and 5-LOX enzymes, based on in vitro and in vivo experiments, from 2020–2024. Structure–activity relationship (SAR) analysis of these compounds revealed four key structural features required for potent dual inhibition of cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX). We refer to these criteria as “The Rule of Four for Inflammation”. Full article

Endometriosis is traditionally conceptualized as a pelvic lesion–centered disease; however, mounting evidence indicates it is a chronic, systemic, and multifactorial inflammatory disorder. This review examines the molecular dialog between ectopic endometrial tissue, the immune system, and peripheral organs, highlighting mechanisms that underlie disease chronicity, symptom variability, and therapeutic resistance. Ectopic endometrium exhibits distinct transcriptomic and epigenetic signatures, disrupted hormonal signaling, and a pro-inflammatory microenvironment characterized by inflammatory mediators, prostaglandins, and matrix metalloproteinases. Immune-endometrial crosstalk fosters immune evasion through altered cytokine profiles, extracellular vesicles, immune checkpoint molecules, and immunomodulatory microRNAs, enabling lesion persistence. Beyond the pelvis, systemic low-grade inflammation, circulating cytokines, and microRNAs reflect a molecular spillover that contributes to chronic pain, fatigue, hypothalamic–pituitary–adrenal axis dysregulation, and emerging gut–endometrium interactions. Furthermore, circulating biomarkers—including microRNAs, lncRNAs, extracellular vesicles, and proteomic signatures—offer potential for early diagnosis, patient stratification, and monitoring of therapeutic responses. Conventional hormonal therapies demonstrate limited efficacy, whereas novel molecular targets and delivery systems, including angiogenesis inhibitors, immune modulators, epigenetic regulators, and nanotherapeutics, show promise for precision intervention. A systems medicine framework, integrating multi-omics analyses and network-based approaches, supports reconceptualizing endometriosis as a systemic inflammatory condition with gynecologic manifestations. This perspective emphasizes the need for interdisciplinary collaboration to advance diagnostics, therapeutics, and individualized patient care, ultimately moving beyond a lesion-centered paradigm toward a molecularly informed, holistic understanding of endometriosis. Full article

Androgenetic alopecia (AGA) is closely associated with oxidative stress and vascular dysfunction, which disrupt nutrient delivery to hair follicles and promote follicle miniaturization. Dihydrotestosterone (DHT) exposure impairs human dermal microvascular endothelial cell (HDMEC) function by inducing mitochondrial disruption, excessive reactive oxygen species (ROS) accumulation, and reduced angiogenic capacity. This study evaluated the protective effects of dihydroisoquinolinone piperidinylcarboxy pyrazolopyridine (DPP), a novel 15-hydroxyprostaglandin dehydrogenase (15-PGDH) inhibitor identified through the AI-based discovery platform DeepZema^®, in DHT-exposed HDMECs. DPP markedly reduced intracellular and mitochondrial ROS levels, restored mitochondrial membrane potential, and increased ATP production, thereby alleviating oxidative stress and supporting mitochondrial function. DPP also enhanced endothelial cell migration and capillary-like tube formation, demonstrating the restoration of angiogenic capacity that is essential for sustaining perifollicular vascularization. Moreover, DPP mitigated stress-associated signaling by reducing the phosphorylation of ERK, JNK, and p38 within the MAPK pathway, thereby suggesting the reestablishment of endothelial homeostasis under DHT-induced stress. Collectively, these findings indicate that DPP preserves endothelial function under DHT-driven oxidative conditions. We suggest that DPP may exert complementary protective effects on both vascular and follicular compartments, supporting its potential relevance in hair follicle regeneration. Full article