Search Results (816)

Background/Objectives: Lithocarpus litseifolius (Hance) Chun, also known as sweet tea, is a traditional Chinese tea-making plant. Acute lung injury (ALI), a life-threatening syndrome with symptoms like hypoxemia and dyspnea, can be triggered by infection or trauma, with high morbidity and mortality. Whether the water extract of Lithocarpus litseifolius (WEL) has therapeutic effects on ALI remains unclear. This study aimed to analyze WEL’s components, establish in vitro cellular inflammation and mouse ALI models, and investigate WEL’s protective effects against LPS-induced ALI. Methods: LC-MS analysis identified 42 compounds in WEL and quantified three key ones. In an LPS-induced mouse ALI model, WEL significantly reduced lung injury severity, lung wet-to-dry ratio, pulmonary edema, and levels of NO, ROS, IL-1β, TNF-α, and MPO in lung tissues and bronchial alveolar lavage fluid. Immunohistochemical analysis showed WEL pretreatment inhibited the upregulation of NLRP3, Caspase-1, and GSDMD-NT expression, mitigated tissue oxidative stress and cell pyroptosis, and alleviated ALI severity in mice. Cellular experiments confirmed WEL’s protective effects via anti-inflammatory, antioxidant actions, and inhibiting cell pyroptosis, with phlorizin and trilobatin as potential key active ingredients. Conclusions: This research demonstrates sweet tea’s significant protective effects against ALI and its potential to alleviate inflammation by inhibiting pyroptosis, providing a theoretical basis for developing new health-promoting functions of sweet tea. Full article

Exposure to stress during early developmental stages correlates with persistent alterations in multiple physiological systems, including the renal system. In rodents, maternal separation (MS) is a widely used experimental model to simulate postnatal adversity. Although this condition affects various renal parameters, a gap persists in knowledge regarding its impact on the functional unit of the kidney and the organization of the parenchyma. Thus, the objective of this systematic review was to analyze the effects of MS on the morphofunctional characteristics of the kidney in rodent models. We developed a protocol a priori following the SYRCLE and PRISMA guidelines and registered it in PROSPERO (CRD420251004703). We searched Web of Science, Scopus, Medline, Embase, BIREME-BVS, and SciELO without language or date restrictions, targeting experimental studies in rodents subjected to MS that evaluated structural, functional, or molecular alterations. Three independent reviewers performed data selection and extraction, and they assessed the risk of bias using the SYRCLE’s RoB tool. We included seven studies that met the eligibility criteria. At the structural level, studies reported cellular infiltrates positive for MPO, CD44, and TLR4, along with increased cortical and medullary microvascular density. Regarding renal function, the included studies described changes in ACE1 and ACE2 activity, oxidative stress, and enzymatic imbalance accompanied by a compensatory antioxidant response. At the molecular level, the studies reported variations in the expression of adrenergic receptors and the renin-angiotensin system. These findings suggest that MS may compromise the organization and functional integrity of the developing kidney, underscoring the need for studies that integrate structural and functional analyses in greater depth. Full article

Microfluidic paper-based analytical devices (µPADs) are ideal for point-of-care diagnostics due to their low cost, compact size, and ease of use. However, current designs have limited multiplexing capabilities, making it difficult to simultaneously detect pathogens and biomarkers in the same sample. In this work, we introduce NanoArrayPAD−X, a novel µPAD design that combines wax-printed microfluidic networks with an array of nanoprobes for the simultaneous detection of multiple targets. This is achieved by distributing the sample through the microfluidic network containing X detection areas. There, targets are captured through physical interactions and recognized by specific antibody-coated nanoprobes released from the nanoprobe array. This generates X dots whose color depends on the concentration of the targets in the sample. A NanoArrayPAD−5 platform capable of detecting five targets was developed to aid in the diagnosis of ventilator-associated pneumonia (VAP). The sensor array could detect Pseudomonas aeruginosa, Klebsiella pneumoniae, Staphylococcus aureus, Escherichia coli, and the inflammatory biomarker myeloperoxidase (MPO) with a total turnaround time of 25 min, which is faster than waiting for an overnight culture and the results of an ELISA. Notably, our prototype successfully detected the targets in 87 bronchial aspirate (BAS) specimens, thus demonstrating the suitability of the platform for analyzing complex samples with sputum-like qualities. These findings establish NanoArrayPAD−X as a promising tool for the rapid, multiplexed screening of respiratory pathogens and biomarkers, with potential for guiding personalized antimicrobial therapy in suspected cases of nosocomial pneumonia. Full article

Objective: Schizophrenia is a chronic psychiatric disorder associated with increased oxidative stress. We aimed to investigate serum myeloperoxidase (MPO), catalase (CAT), and malondialdehyde (MDA) levels and their diagnostic value in schizophrenia. Methods: Sixty patients with schizophrenia, diagnosed according to DSM-V criteria, and 65 age- and sex-matched healthy controls were enrolled. Clinical severity was assessed with the Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impression (CGI). Serum MPO and CAT were measured using ELISA, and MDA levels were determined spectrophotometrically. Receiver operating characteristic (ROC) analysis was performed to assess diagnostic performance. Results: Compared with controls, schizophrenia patients demonstrated significantly higher serum MDA (5.64 vs. 3.42 pg/mL, p < 0.001), MPO (77.25 vs. 31.42 ng/mL, p < 0.001), and CAT (22.06 vs. 6.58 ng/mL, p < 0.001) levels. Subgroup analysis revealed consistently increased values across patients receiving typical, atypical, or combined antipsychotics. ROC analysis indicated good diagnostic accuracy: AUC = 0.884 for MDA (cut-off: 3.79 pg/mL), AUC = 0.882 for MPO (cut-off: 34.56 ng/mL), and AUC = 0.875 for CAT (cut-off: 9.38 ng/mL), all p < 0.001. Combined analysis of MPO, CAT, and MDA yielded superior diagnostic performance (AUC = 0.995; sensitivity = 98.3%). MPO was positively correlated with PANSS-N scores (r = 0.275, p = 0.033), and both MPO and CAT were correlated with CGI severity scores. Conclusions: Elevated MPO, CAT, and MDA levels indicate increased oxidative stress in schizophrenia. MPO may also be associated with negative symptom severity. These findings suggest potential utility of oxidative stress biomarkers as adjunctive diagnostic tools, although results should be considered preliminary and validated in larger, drug-naïve, and longitudinal samples. Full article

People living with the human immunodeficiency virus (PLWH) are continually subjected to challenges involving the development of non-acquired immunodeficiency syndrome (AIDS)-related comorbidities despite the effectiveness of highly active antiretroviral therapy (HAART). Exacerbated oxidative stress, which is intrinsically linked to chronic inflammation, is implicated in non-AIDS comorbidities, including the increased risk of cardiovascular disease (CVD) observed in PLWH. Here, we review evidence on the potential pathological implications of myeloperoxidase (MPO), a leukocyte-derived enzyme and a key mediator of oxidative stress and inflammation, in driving CVD-related complications in PLWH. A systematic review approach was taken to identify relevant clinical studies through searches of Cochrane Libraries, PubMed, Web of Science, ScienceDirect, and Google Scholar, up to the 30 June 2025. The summarized data appraised clinical studies (n = 14) on adults (n = 1445) with a mean age of 45 years reporting on the association between MPO and enhanced lipid peroxidation marked by elevated concentrations of oxidized low-density lipoprotein cholesterol (oxLDL-C) in PLWH. Such results were consistent with elevated inflammatory markers, including high sensitivity C-reactive protein (hsCRP), which was also linked with endothelial dysfunction. There is a lack of evidence linking the duration of HAART to MPO levels or an increased risk of CVD. However, there is room to explore whether enhanced levels of oxLDL-C, in association with sustained MPO activation, could drive CVD risk in PLWH. The present review provides essential information on the pathological relevance of MPO in endothelial dysfunction and CVD risk in PLWH. Full article

Background and Objectives: To investigate whether myeloperoxidase (MPO)-antineutrophil cytoplasmic antibody (ANCA) titres at diagnosis are associated with the risk of end-stage kidney disease (ESKD) progression in patients with microscopic polyangiitis (MPA) treated with rituximab. Materials and Methods: This retrospective cohort study included 34 patients with MPA who received rituximab. Clinical data, including MPO-ANCA titres at diagnosis and ESKD progression during follow-up, were assessed. Receiver operating characteristic (ROC) curve analysis was performed to assess whether MPO-ANCA titres could predict ESKD progression. The optimal cut-off value of MPO-ANCA titres was determined where the sum of sensitivity and specificity was at a maximum. Based on this cut-off value, patients were categorised into two groups, and the relative risk (RR) of ESKD progression was estimated. Results: During a median follow-up of 39.5 months, seven patients (20.6%) progressed to ESKD. ROC curve analysis showed a significant inverse association between MPO-ANCA titres and ESKD progression (AUC 0.254, 95% confidence interval [CI] 0.046, 0.462 p = 0.048). The optimal cut-off of MPO-ANCA titres was 81.0 IU/mL, which yielded a sensitivity and specificity of 70.4% and 85.7%, respectively. The RR of ESKD progression was significantly higher in those with MPO-ANCA titres ≤ 81.0 IU/mL than in those with MPO-ANCA titres > 81.0 IU/mL (42.9% vs. 5.0%, RR 14.250, 95% CI 1.469, 138.271). Conclusions: Lower MPO-ANCA titres at diagnosis may be associated with a higher risk of ESKD progression in rituximab-treated MPA patients. These findings suggest that MPO-ANCA titres may be useful in guiding therapeutic decisions for MPA. Full article

Mercury exposure has been linked to male infertility. Given that mercury chloride (HgCl₂) may promote an oxido-inflammatory milieu associated with pathophysiological derangements, it is hypothesised that Thymoquinone (TQ), an antioxidant and anti-inflammatory agent, may mitigate the gradual harmful effects of mercury exposure on rat testes, epididymis, and hypothalamus, as these organs are vital to reproductive function. To test this hypothesis, 40 rats (strain: Wistar; sex: male) were randomly assigned to five cohorts of eight rats each. After a 7-day acclimation, treatments were dispensed for 28 consecutive days accordingly: Cohort I: distilled water only, as control; Cohort II: HgCl₂ only (20 µg/mL); Cohort III: TQ only (2.5 mg/kg); Cohort IV: HgCl₂ + TQ (20 µg/mL + 2.5 mg/kg); and Cohort V: HgCl₂ + TQ (20 µg/mL + 5 mg/kg). Co-treatment with TQ preserved the body and organ weight of the HgCl₂ exposed animals. However, TQ did not reduce HgCl₂-induced dysfunction in sperm function and morphology. The serum follicle-stimulating hormone (FSH), luteinising hormone (LH), and testosterone were increased significantly (p < 0.05) by TQ co-treatment, while decreasing the prolactin level. TQ administration also increased (p < 0.05) testicular enzymes, including alkaline phosphatase (ALP), lactate dehydrogenase (LDH), acid phosphatase (ACP), and glucose-6-phosphate dehydrogenase (G6PD) activities, which HgCl₂ decreased. TQ administration increased (p < 0.05) HgCl₂-induced decreases in catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione (GSH), glutathione-s-transferase (GST), and total sulfhydryl group (TSH) levels in the testes, epididymis, and hypothalamus of experimental rats. Further, TQ reduced HgCl₂-mediated increases in RONS-reactive oxygen and nitrogen species; LPO–lipid peroxidation; PC–protein carbonyl formation; and XO–xanthine oxidase activity. Furthermore, levels of inflammatory biomarkers, including tumour necrosis factor alpha (TNF-α), nitric oxide (NO), interleukin-1 beta (IL-1β), and myeloperoxidase (MPO), were decreased (p < 0.05) in the co-treated groups, with a higher dose of TQ (5.0 mg/kg) showing a more pronounced protective effect. Additionally, TQ co-administration increased Bax and decreased Bcl-2 and p53 protein levels (p < 0.05), thereby protecting the rats’ testes, epididymis, and hypothalamus from HgCl₂-induced apoptosis. Molecular docking simulation analysis revealed TQ interaction dynamics with PPAR-α and PPAR-δ to suppress NF-kB-mediated pro-inflammatory sequela as well as activate Nrf-2-mediated antioxidant defence system. These predicted biological effects of TQ resonate with the findings from the in vivo studies. Therefore, supplementation with TQ may help reduce chemical-induced toxicities, including HgCl₂‘s reproductive toxicity. Full article

Selenium nanoparticles (Se NPs) have received increasing attention as a new alternative source to other forms of selenium in nutritional dietary supplements; however, the limited stability and pronounced tendency of selenium nanoparticles (Se NPs) to aggregate in aqueous environments have significantly constrained their practical applications. In this study, Poria cocos polysaccharide-modified Se NPs (PCP-Se NPs) were synthesized by the selenite/ascorbic acid chemical reduction method. PCP-Se NPs exhibited a uniformly dispersed spherical morphology with an average particle size of 66.64 ± 0.30 nm, and displayed an amorphous crystal structure. Compared to unmodified Se NPs, the PCP-Se NPs exhibited low Se release (8.83 ± 0.73%) after simulated gastrointestinal digestion, and they had excellent storage stability and salt ion stability. PCP-Se NPs exhibited potent antioxidant activity manifested by the effective scavenging of DDPH and ABTS radicals. PCP-Se NPs were efficiently internalized by RAW264.7 cells and released into the cytoplasm by a lysosomal escape mechanism, thereby effectively reducing intracellular inflammatory factor levels (the levels of MPO, NO, iNOS, TNF-α, IL-1β, and IL-10 in the PCP-Se NPs treatment group were 0.38 ± 0.013-fold, 0.26 ± 0.02-fold, 0.36 ± 0.02-fold, 0.57 ± 0.03-fold, 0.35 ± 0.02-fold, and 2.07 ± 0.16-fold that of the LPS group, respectively), alleviating oxidative stress (the levels of CAT, SOD, GSH, and MDA in the PCP-Se NP-treated group were 2.48 ± 0.02-fold, 1.91 ± 0.11-fold, 3.16 ± 0.28-fold, and 0.46 ± 0.03-fold that of the LPS group, respectively), and maintaining mitochondrial membrane potential stability. This study provides a basis and reference for improving the stability of Se NPs and developing novel selenium-enriched dietary supplements. Full article

In recent decades, chemotherapy has significantly improved cancer survival, yet its adverse effects on non-cancerous tissues raise increasing concerns. In this context, growing attention has been focused on natural compounds that may be useful in mitigating the undesirable effects of chemotherapeutic agents. Here, we aimed to demonstrate that Cytosporone B (CsnB) is a potent agent for counteracting the cardiovascular effects induced by Imatinib. To this end, 12-week-old male Wistar rats were studied; they were divided into three groups as follows: (1) control, (2) Imatinib-treated (Imatinib: 60 mg/kg/day, per os), (3) Imatinib + CsnB-treated (CsnB: 5 mg/kg/day, i.p.). After the two-week-long experimental period, rats were euthanized. Their hearts were used for the following biochemical measurements: NADPH oxidase (NOX4), high mobility group box 1 (HMGB1), peptidylarginine deiminase 4 (PAD4), inducible nitric oxide synthase (iNOS) expression, tumor necrosis factor-alpha (TNF-α) level, and myeloperoxidase (MPO) activity. Imatinib caused a marked upregulation of key inflammatory and oxidative markers, including HMGB1, TNF-α, MPO, iNOS, PAD4, and NOX4 in cardiac tissue; however, CsnB treatment mitigated these elevations, implying its role in opposing Imatinib-induced inflammatory and oxidative processes in the heart. Our findings suggest that CsnB holds promise as a cardioprotective agent capable of modulating Imatinib-induced adverse cardiac effects. Full article

Inflammatory bowel disease (IBD) is a chronic immune-mediated condition of the gastrointestinal tract, characterized by dysregulated inflammatory responses throughout the gastrointestinal tract. It includes two major phenotypes, Crohn’s disease (CD) and ulcerative colitis (UC), which present with varying gastrointestinal and systemic symptoms. The pathophysiology of IBD is multifactorial including genetic predisposition, mucosal and epithelial dysfunction, environmental injury, and both innate and adaptive immune response abnormalities. Several predisposing genetic factors have been associated with IBD explaining the strong hereditary risk for both CD and UC. For example, Caspase Recruitment Domain 9 (CARD9) variant rs10781499 increases risk for IBD, while other variants are specific to either CD or UC. CD is related to loss-of-function mutations in the nucleotide oligomerization domain containing the protein 2 (NOD2) gene and Autophagy-Related 16-like 1 (ATG16L1) gene. UC risk is increased particularly in Chinese populations by the A-1661G polymorphism of the Cytotoxic T-lymphocyte antigen 4 (CTLA-4) gene. This abnormal CTLA-4 interferes with B- and T-cell responses causing predisposition to autoimmune conditions. Previous studies suggested that IBD results from breakdown of the adaptive immune system, primarily of T-cells. However, new evidence suggests that a primary breakdown of the innate immune system in both CD and UC increases susceptibility to invasion by viruses and bacteria, with a compensatory overactivation of the adaptive immune system as a result. When this viral and microbial invasion continues, further damage is incurred, resulting in a downward cycle of further cytokine activation and epithelial damage. Released biomarkers also affect the permeability of the epithelial membrane, including lactoferrin, nitric oxide (NO), myeloperoxidase (MPO) and its activation of hypochlorous acid, matrix metalloproteinases (MMPs), especially MMP-9, omentin-1, and others. Increased macrophage and dendritic cell dysfunction, increased neutrophil activity, increased numbers of innate lymphoid cells, increased T-cells with decreased regulatory T-cells (Tregs), and changes in B-cell populations and immunoglobulin (Ig) functions are all associated with IBD. Finally, treatment of IBD has typically consisted of medical management (e.g., aminosalicylates and corticosteroids) and lifestyle modification, and surgical intervention in extreme cases. New classes of medications with more favorable side effect profiles include anti-integrin antibodies, vedolizumab, etrolizumab, and carotegrast methyl. Additionally, fecal microbiota transplant (FMT) is a newer area of research for treatment of IBD along with TNF-blockers, JAK inhibitors, and S1PR modulators. However, expense and long preparation time have limited the usefulness of FMT. Full article

Inflammatory bowel disease continues to pose substantial therapeutic challenges in modern gastroenterology. This study systematically evaluated the anti-colitis efficacy of Cucumaria frondosa tentacles hydrolysates (CFTHs) using a dextran sulfate sodium (DSS)-induced murine colitis model. Characterized by enhanced stability and solubility with molecular weights below 1000 Da, administration of CFTHs demonstrated a significant mitigation in colitis pathology. Therapeutic outcomes included an improved splenic index, attenuated colonic mucosal damage, and substantial decreases in serum pro-inflammatory cytokines. Relative to the DSS group, the MPO value in the CFTHs-H group decreased by 27.6%, and the IL-6 value exhibited a reduction of 33%. Metagenomic profiling revealed that CFTHs mediated gut microbiota modulation, particularly the enrichment of beneficial Bacteroidetes and suppression of pro-inflammatory Proteobacteria. Metabolomic analysis identified elevated colonic concentrations of anti-inflammatory metabolites such as gamma-linolenic acid and prostaglandin I2, suggesting a microbiome–metabolome crosstalk in the therapeutic mechanism. These multi-omics findings in a murine model suggest that CFTHs may represent a promising candidate for future studies as a nutraceutical intervention for inflammatory bowel disorder. This intervention may operate through mechanisms that include simultaneous immunomodulation, microbiota restoration, and metabolic reprogramming. Full article

High-density lipoproteins (HDLs) protect against atherosclerosis through their antioxidant, anti-inflammatory, and other beneficial properties. Although interest is increasing in uncovering both physiological and external factors that influence these functions, definitive evidence remains lacking in this area. To fill this gap, we assessed for the first time how intake of saturated and unsaturated fatty acids and dietary antioxidants affects key HDL-associated proteins. We observed that myeloperoxidase (MPO) activity, a marker of HDL oxidation, was inversely correlated with total polyunsaturated fatty acids (PUFAs), omega-3 and omega-6 intake (p < 0.05), polyphenols (p < 0.001), and overall antioxidant capacity (p < 0.05). Levels of lipoprotein-associated phospholipase A2 also decreased with higher antioxidant consumption (p < 0.05). By contrast, glutathione peroxidase 3 (Gpx3) activity, a protective HDL enzyme, increased in tandem with omega-3 and antioxidant intake. Finally, a composite HDL-antioxidant/anti-inflammatory score integrating all measured proteins rose in association with total PUFAs (p < 0.001), omega-6 (p < 0.001), omega-3 (p < 0.01), polyphenols, and total antioxidants (p < 0.05). These findings suggest that higher dietary PUFA, especially omega-6, and antioxidant intake may enhance HDL’s atheroprotective properties. Full article

Cardiovascular diseases (CVDs) are increasingly being defined not only in terms of metabolic or purely vascular disorders, but also as complex immunometabolic disorders. One of the most groundbreaking discoveries in recent years is the role of neutrophil extracellular networks (NETs/NENs) as a key link between chronic vascular wall inflammation and thrombotic processes. In this article, we present a synthetic overview of the latest data on the biology of NETs/NENs and their impact on the development of atherosclerosis, endothelial dysfunction, and the mechanisms of immunothrombosis. We highlight how these structures contribute to the weakening of atherosclerotic plaque stability, impaired endothelial barrier integrity, platelet activation, and the initiation of the coagulation cascade. We also discuss the modulating role of classic risk factors such as hypertension, dyslipidemia, and exposure to tobacco smoke, which may increase the formation or hinder the elimination of NETs/NENs. We also focus on the practical application of this knowledge: we present biomarkers associated with the presence of NETs/NENs (cfDNA, MPO–DNA complexes, CitH3, NE), which may be useful in diagnostics and risk stratification, and we discuss innovative therapeutic strategies. In addition to classic methods for indirectly inhibiting NET/NEN formation (antiplatelet, anti-inflammatory, and immunometabolic agents), we present experimental approaches aimed at their neutralization and removal (e.g., DNase I, elastase, and myeloperoxidase inhibitors). We pay particular attention to the context of cardiac and cardiac surgical procedures (Percutaneous Coronary Intervention-PCI, coronary artery bypass grafting-CABG), where rapid NET/NEN bursts can increase the risk of acute thrombotic complications. The overall evidence indicates that NETs/NENs represent an innovative and promising research and therapeutic target, allowing us to view cardiovascular diseases in a new light—as a dynamic interaction of inflammatory, atherosclerotic, and thrombotic processes. This opens up new possibilities in diagnostics, combination treatment and personalisation of therapy, although further research and standardization of detection methods remain necessary. Full article

Bladder dysfunction, particularly overactive bladder (OAB), is increasingly recognized as a clinical concern in patients with sickle cell disease (SCD), yet its pathophysiological mechanisms remain poorly understood. This study investigated the relationship between oxidative stress, inflammation, and bladder dysfunction in the Townes transgenic SCD mouse model. Cystometric analysis revealed that SCD mice exhibit an OAB phenotype, characterized by increased frequencies of voiding and non-voiding contractions and reduced bladder compliance. In vitro functional assays demonstrated detrusor hypocontractility in SCD mice, associated with a significant reduction in carbachol- and EFS-induced contractions and downregulation of muscarinic M3 receptor expression. Purinergic signaling and calcium-dependent contractility remained preserved. Molecular analyses showed increased mRNA expression of NOX-2 and IL-1β, and elevated protein levels of 3-nitrotyrosine and myeloperoxidase (MPO) activity, indicating redox imbalance and chronic inflammation in bladder tissue. Together, these changes suggest that oxidative and nitrosative stress, combined with inflammation, contribute to bladder remodeling and dysfunction in SCD. This is the first study to characterize bladder alterations in Townes SCD mice, establishing this model as a valuable tool for investigating lower urinary tract complications in SCD. Our findings provide mechanistic insight into the genitourinary manifestations of SCD and identify redox and inflammatory pathways as potential therapeutic targets for bladder dysfunction in affected individuals. Full article

Background: This study aimed to change the current concept of diabetic macular edema (DME) management through (1) early categorization of our DME patients into either responders or non-responders after the first intravitreal Ranibizumab (IVR) injection, and (2) finding a suitable clinical–biochemical diagnostic panel to identify the possible cause(s) of non-response in each non-responder and changing the treatment plan in each particular patient accordingly. Patients and methods: Our study included 64 eyes of 40 patients with DME (Group A, DME patients) and 40 eyes of 40 healthy individuals matched for age and sex (Group B, controls). Blood and aqueous samples were collected from the study participants before and one month after IVR injection. The DME patients were further subdivided into responders and non-responders according to their response to the first IVR injection. Lymphocyte activation markers, NETosis markers, angiogenic factors, astrocytes, innate immunity, and inflammasome markers were assessed in both groups. Results: Multivariate regression analysis revealed that macular ischemia, aqueous levels of hexokinase 1, SELL CD62L, ELANE, MPO, VEGFA, and SEMA4D were the most significant factors affecting the response to IVR (p < 0.05). Conclusions: defining our DME patients as responders and non-responders after the first IVR injection, combined with potential utilization of a clinical–biochemical panel (macular ischemia- PCR array of combined Hexokinase 1, MPO, and SEMA4D) in each non-responder, may represent a good starting point for changing the current DME management strategy. Full article