Search Results (489)

Plenty of nano-antimicrobial materials have been developed successively, aiming to address severe clinical challenges such as wound healing disorders and high postoperative mortality rates caused by drug-resistant bacterial infections. However, their reliance on external stimuli (light, thermal energy, or exogenous H₂O₂ addition) for bactericidal activation severely hampers clinical translation from bench to bedside. Herein, we report an engineered Cu/CeO₂ nanoplatelet (NP) system that functions as a stimulus-independent, time-dependent nano-antibiotic against methicillin-resistant Staphylococcus aureus (MRSA), while also exhibiting broad-spectrum antibacterial activity. In a skin wound model infected with MRSA, topical application of only 1 μg/mL achieved near-complete wound closure within 10 days. The satisfactory therapeutic effect is concluded: (1) Cu/CeO₂ NPs continuously release Cu²⁺, which damages the integrity of bacterial cell membranes and achieves efficient sterilization. (2) The antioxidant stress capacity, peroxidase, and catalase-like activity effectively alleviate oxidative stress and hypoxia conditions in the infected microenvironment, and synergistically exert multiple biological effects such as anti-inflammatory, promoting collagen deposition and the formation of new blood vessels. This study not only provides a feasible pathway for the clinical application of antibacterial nano-materials, but also offers theoretical support and practical examples for the rational design of multifunctional nano-antibiotics. Full article

Background: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) represents a group of rare systemic autoimmune disorders marked by inflammation and damage to small- and medium-sized blood vessels. The clinical presentation of AAV is highly variable, ranging from isolated organ involvement to severe, life-threatening multisystem disease, posing significant challenges in diagnosis, treatment, and prognosis. Objective: To demonstrate the clinical heterogeneity and different outcomes in three pediatric cases of ANCA-positive disease and emphasize the importance of integrating clinical findings with laboratory and imaging investigations for accurate diagnosis. Methods: We present three pediatric patients (ages 12–15 years) with ANCA-positive results but distinct clinical presentations, evaluated at the Children’s Emergency Hospital “Louis Turcanu”, Timisoara, between 2020 and 2024. All cases were investigated according to EULAR/PRINTO/PReS criteria for pediatric vasculitis. Results: Case 1 (PR3-ANCA positive) developed severe multi-organ involvement, including granulomatosis with polyangiitis (GPA) with pulmonary hemorrhage, pericarditis, thrombotic events, and renal impairment, requiring intensive immunosuppression with cyclophosphamide, rituximab, and mycophenolate mofetil, ultimately developing chronic kidney disease stage 3a. Case 2 (BPI-ANCA positive) presented with purpuric lesions and painless joint swelling, responding favorably to corticosteroid therapy with subsequent remission. Case 3 (MPO-ANCA) manifested as polyarticular arthritis without other organ involvement and was ultimately diagnosed as seronegative juvenile idiopathic arthritis (JIA), achieving complete remission with adalimumab therapy. Conclusions: This case series highlights the diverse clinical and biological features of ANCA-positive conditions in children, emphasizing that ANCA positivity requires careful clinical correlation as it may indicate true vasculitis requiring aggressive treatment or alternative diagnoses such as JIA with incidental ANCA positivity. Tailored therapeutic strategies based on clinical presentation and continued research are essential to improve patient outcomes. Full article

While diabetic retinal disease (DRD) has classically been viewed as a microvascular complication, emerging evidence places the photoreceptor at the center of its pathogenesis. Recognizing this central role provides a critical framework for resolving a major clinical paradox in diabetes: why the retina exhibits profound susceptibility to hyperglycemic damage, whereas closely related neural tissues like the brain are mostly spared. In this review, we synthesize the evidence for photoreceptor-driven DRD pathology by evaluating two primary mechanistic paradigms. In the first, hyperglycemia-induced damage to the blood vessels limits perfusion, creating an ischemic environment that selectively devastates tissues dependent on exceptionally high blood flow and energy delivery—specifically, the photoreceptors. In the second paradigm, hyperglycemia induces a direct shift in the metabolic profile of photoreceptors, triggering oxidative stress and dysregulated lipogenesis that subsequently place pathological strain on the local microvasculature. Regardless of whether the initial insult is vascular or neuronal, the photoreceptor remains the critical node of disease progression. Because current and investigational DRD treatments predominantly target downstream vascular consequences, exploring these dual mechanisms highlights an urgent need and a significant opportunity to develop novel therapies that target the photoreceptor to address DRD at its root. Full article

Individuals with diabetes mellitus (DM) experience impaired wound healing, where the healing process is often compromised by a complex, hostile microenvironment characterized by persistent inflammation, high oxidative stress, and dysfunctional angiogenesis. The hyperglycemic environment damages the blood vessels and disturbs the normal hypoxia-induced upregulation of vascular endothelial growth factors, causes poor vascularization and insufficient production of new blood vessels, and leads to impaired perfusion and thickened and dysfunctional capillary basement membranes, which reduce blood flow to the wound, leading to delayed wound healing. Mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) are the main effectors of intercellular communication and have emerged as a potent cell-free strategy for the acceleration of tissue repair. MSC-EVs can be isolated from various adult tissues, but increasing evidence suggests that placental MSC-derived EVs (PMSC-EVs) possess distinct clinical and biological advantages for enhancing diabetic wound healing. Placentas are unique cell sources for PMSCs, which can be easily acquired non-invasively from a discarded placenta and is ethically acceptable, and have superior proliferative capacity. The cargo of PMSC-derived EVs contains macromolecules such as proteins, mRNA, miRNA, and lipids, which may be tailored for fetomaternal tolerance and translates to unmatched immunomodulatory potential for resolving chronic diabetic inflammation. The PMSC-derived EVs also aid in enhancing multiple pathways, including modulation of inflammation, angiogenesis, and epithelial proliferation, that lead to increased wound healing. This article will highlight the unique advantages, specific mechanisms, and limitations of PMSC-derived EVs as an innovative non-cellular therapeutic modality in restoring vital repair processes and enhancing diabetic wound healing. Full article

Background/Objectives: Arterial hypertension might lead to serious organ damage and complications like hypertensive retinopathy. The retina is the only place in the human body where microscopic blood vessels can be directly investigated. This enables early diagnosis of arterial hypertension-mediated organ damage. Untreated hypertensive retinopathy leads to vision loss in its advanced stages. There are many methods of assessing changes in the arterioles; however, the most accurate is adaptive optics (RTX1™ device with AODetectArtery software, ver. 3.0., Imagine Eyes, Orsay, France). It provides a resolution of 1.6 μm, which is superior to conventional imaging techniques. Optical coherence tomography angiography can serve as an early, minimally invasive marker of microvascular damage. Across the studies analyzed, the WLR (Wall-to-Lumen Ratio) exhibited significantly higher values when comparing individuals with hypertensive retinopathy to normotensives (0.31 vs. 0.26). The main aim of this review is to present the application of adaptive optics in the early diagnosis of hypertensive retinopathy. Methods: The search strategy included 267 original studies, among which 12 were selected to be described and analyzed in this review based on criteria including original research and studies performed on humans with hypertensive retinopathy. Results: RTX1™ enables the assessment of arterial parameters such as the Wall Thickness (WT), Lumen Diameter (LD), Outer Diameter (OD), Wall-to-Lumen Ratio (WLR) and Wall Cross Sectional Area (WCSA). These parameters differ depending on the arterial hypertension. The WLR was identified to be the parameter that differs in the vast majority of analyzed studies when comparing hypertensive patients to normotensive patients. Vascular parameters were also found to change depending on different organisms’ states, treatment applications and etiological causes of disease. Furthermore, changes in retinal arterial parameters were associated with increased cardiovascular risk in observational studies. RTX1™ was also identified to provide very good intra- and interobserver variability. Conclusions: RTX1™ is a valuable tool in the examination of arterial vessels and in establishing associations between retinal vascular parameters and a patient’s clinical state. Full article

Acute ischemic stroke (AIS) is characterized by complex interactions among vascular occlusion, endothelial injury, and inflammatory activation, which collectively influence clinical outcomes. Increasing attention has focused on the endothelial glycocalyx, a critical regulator of vascular permeability, mechanotransduction, and inflammatory signaling. Disruption of the endothelial glycocalyx during ischemia and subsequent reperfusion contributes to blood–brain barrier (BBB) dysfunction and secondary brain injury. Mechanical thrombectomy has emerged as the reference standard treatment for large vessel occlusion in AIS. This review synthesizes current evidence on endothelial glycocalyx degradation and associated inflammatory cascades in cute ischemic stroke, with particular emphasis on patients undergoing mechanical thrombectomy. We examine the mechanisms underlying endothelial and BBB injury, ischemia–reperfusion-mediated vascular dysfunction, and systemic inflammatory responses (SIRS). In addition, the potential clinical relevance of circulating biomarkers indicative of endothelial glycocalyx shedding and endothelial damage is discussed. By integrating molecular pathophysiology with contemporary reperfusion strategies, this review highlights the importance of endothelial protection as a potential adjunct to mechanical thrombectomy. While mechanical thrombectomy remains the gold standard therapy for AIS due to large vessel occlusion, targeting endothelial glycocalyx integrity and post-reperfusion inflammation may represent a promising approach to optimizing neurological outcomes and reducing complications. Further research is required to elucidate specific pathophysiological mechanisms and to develop targeted therapeutic strategies aimed at reducing stroke-related morbidity and mortality. Full article

(1): Endotoxins are components of Gram-negative bacteria. Uptake can induce allergies, nausea, or sepsis. These responses are triggered by an activation of the immune system. Endothelial cells, lining blood vessels, are the first to be exposed to circulating LPA. Activation can dramatically affect the blood system, such as the formation of thrombi. This study aimed to clarify whether the activation of primary human venous endothelial cells (HUVECs) by LPA could be reduced by the addition of an Arthrospira platensis (AP) extract. (2): HUVECs were cultured for 24 h in cell culture medium supplemented with different concentrations of AP (50, 100, 200 µg/mL). Then 2.5 µg/mL of LPA was added. Cell morphology, viability, cell proliferation, cell membrane integrity, cell metabolism, and cell function were examined after two and four days. (3): Treatment with LPA alone negatively affected HUVEC growth, viability, cell membrane integrity, and metabolic activity. Adding AP to the culture medium had a positive influence on these effects, with 100 µg/mL proving to be the most effective dose. (4): The results clearly revealed that an extract of AP has the potential to reduce the damage to the venous endothelium when exposed to lipopolysaccharides, in particular at a concentration of 100 µg/mL. Full article

Background/Objectives: Diabetic wound healing faces significant challenges due to the harsh microenvironment of wounds such as high blood glucose levels, excessive inflammation, persistent infection, upregulated reactive oxygen species (ROS), and damaged new blood vessels. Therefore, developing hydrogel dressings with microenvironmental regulation functions has become an important strategy in treating diabetic wounds. Methods: In this study, an ultraviolet in situ crosslinked hydrogel (D@H/E) was developed using methacrylic anhydride modified hyaluronic acid (HA-MA) and glycidyl methacrylate modified ε-polylysine (EPL-GMA), loaded with the iron chelating agent desferrioxamine (DFO). The physicochemical and biochemical properties of the hydrogel were comprehensively characterized, and its efficacy as a dressing for diabetic wounds was evaluated in a STZ-induced hyperglycemic mouse model. Results: This hydrogel demonstrated remarkable multidimensional effects by alleviating oxidative stress damage, inhibiting bacterial infection, regulating inflammatory responses, mitigating ferroptosis, and promoting cell migration and tubule formation. Specifically, the DFO-loaded hydrogel achieved a high DPPH radical scavenging efficiency of 80.8% and exhibited excellent antibacterial activity, with over 99.8% inhibition against both S. aureus and E. coli. In streptozotocin (STZ)-induced diabetic mice, the hydrogel accelerated wound closure to near completion by day 14. Mechanistically, it significantly upregulated CD206 expression to promote M2 macrophage polarization, upregulated the expression of angiogenesis-related factors to promote angiogenesis at the wound site, and enhanced GPX4 expression to alleviate ferroptosis. Conclusions: By orchestrating multi-dimensional synergy that combines ROS scavenging, infection control, immune regulation, and anti-ferroptosis, this D@H/E hydrogel system effectively remodels the harsh diabetic wound microenvironment, offering a promising platform for chronic wound management. Full article

Diabetic retinopathy is a prevalent condition and a major public health concern due to its detrimental impact on eyesight. Diabetes is a root cause of its development and damages small blood vessels caused by prolonged high blood sugar levels. The degenerative consequences of diabetic retinopathy are irrevocable if not diagnosed in the early stages of its progression. This ailment triggers the development of retinal lesions, which can be identified for diagnosis and prognosis. However, lesion detection is challenging due to their similarity in intensity profiles to other retinal features, inconsistent sizes, and random locations. This research evaluates a custom deep learning network for classifying retinal images and compares it with the state-of-the-art classifiers. The novel preprocessing method is introduced to reduce the complexity of the diagnostic process and to enhance classification performance by adaptively enhancing images. Despite being a shallow network, the proposed model yields competitive results with an accuracy of 87.66% and an F1-score of 0.78. The evaluation metrics indicate that class imbalance affects the performance of the proposed model despite using the weighted cross-entropy loss. The future contribution will be the inclusion of generative adversarial networks for generating synthetic images to balance the dataset. This research aims to develop a robust computer-aided diagnostic system as a second interpreter for ophthalmologists during the diagnosis and prognosis stages. Full article

Healing skin wounds is still difficult in many clinical situations, especially when the wounds are chronic or infected. These wounds often stay inflamed for long periods, and the risk of bacterial invasion is high. Oxidative stress tends to increase as well, while the formation of new blood vessels is often inadequate. Because of these factors, wound repair depends on the proper coordination of several biological events. These include basic antimicrobial activities, the control and resolution of inflammation, protection against oxidative damage, the rebuilding of collagen structures, and the development of new vascular networks. Traditional Chinese Medicine (TCM) provides many active compounds. These compounds work on many targets and through different pathways. They show good potential in wound treatment. But many TCM compounds have poor solubility in water. They are also unstable, have low bioavailability, and do not pass through the skin easily. These problems limit their use in clinical settings. Nanotechnology offers new ways to solve these problems. Nanodelivery systems can improve the solubility and stability of active compounds. They can also help the compounds enter the skin and stay in the wound area. Many types of nanocarriers have been developed, such as liposomes, polymer nanoparticles, nanogels, and inorganic nanomaterials. These systems can also provide controlled release or release that responds to the wound environment. This can make the treatment more accurate. In this review, we summarize how major TCM-derived compounds support wound repair and describe the biological mechanisms behind their effects. We also discuss recent nanodelivery approaches that aim to strengthen these therapeutic actions. These combinations can improve antibacterial performance, shape the immune response, reduce reactive oxygen species, and help the skin close more quickly. We also point out several challenges, such as concerns about material safety, the need for more consistent herbal extraction methods, gaps in mechanistic understanding, and the difficulty of producing these formulations on a large scale. Taken together, these points suggest that nanodelivery approaches using TCM-derived compounds still need more careful study and steady improvement before they can be used more widely in wound care. Full article

Background and Objectives: Optic disc drusen (ODD) are deposits in the optic nerve head that can look like true swelling, and in some patients, slowly damage the optic nerve and cause visual field loss. We aimed to identify which eyes are most likely to worsen over time using common clinic tests. Methods: We studied 131 adults with OCT-confirmed ODD who also had OCT-angiography (a scan that measures small blood vessels around the optic nerve) and repeated visual field tests over at least 18 months. We measured (1) the size of the drusen (maximum drusen height), (2) blood vessel density around and inside the optic nerve, and (3) change in visual field performance over time. “Fast progression” was defined as visual field worsening of ≥0.5 dB per year. Results: Eyes with superficial ODD had larger drusen than buried ODD (382.6 ± 110.9 vs. 247.2 ± 92.8 µm; p < 0.001) and more frequent visual field defects (78.6% vs. 58.7%; p = 0.02). When blood vessel density around the optic nerve was low, fast progression was much more common (52.3%) than in the middle (16.3%) or highest groups (13.6%; p < 0.001). In the adjusted model, fast progression was more likely with superficial ODD (OR 6.3) and larger drusen (OR 2.0 per 100 µm), and less likely when the vessel density was higher (OR 0.8 per 1% increase). Adding the vessel measurements improved the prediction accuracy (AUC 0.8 → 0.9; p = 0.011). Conclusions: Combining drusen size and blood vessel measurements helps identify ODD patients at higher risk of faster visual field loss and may guide closer follow-up. Full article

The high concentration of the inflammatory cytokine IL-36 in the serum of patients with type 2 diabetes mellitus (T2DM), along with the reduced renal damage observed in IL-36R knockout mice following ischemia–reperfusion-induced acute kidney injury, suggests a significant association between IL-36 activity and diabetic complications such as diabetic nephropathy (DN). It is also known that minor structural alterations in glomerular tissues can lead to changes in blood vessel pressure, potentially contributing to the development of DN, with inflammation acting as a triggering factor. However, further studies are needed to confirm this relationship. In this study, we observed that mesangial (MES-SV40) cells cultured under high-glucose conditions produced IL-36α in a dose-dependent manner. This cytokine production was also detected in mesangial cells from the glomerular tissues of mice with a high-calorie diet-induced T2DM, whereas healthy mice did not show such expression. In addition, we observed that mouse endothelial cells (SVECs) showed increased tubule formation in co-culture with MES-SV40 cells that had been previously exposed to 30 mmol/L glucose, as well as with the supernatant from these cells. IL-36R expression was confirmed in endothelial cells, as well as the angiogenic effect of IL-36α. Given that elevated VEGF levels have been reported in patients with DN by other authors, our results suggest that IL-36 produced by mesangial cells under high-glucose conditions may promote angiogenesis in glomerular tissues, potentially initiating the development of diabetic nephropathy. Full article

Inflammation and oxidative stress are key mechanisms in aging, contributing to neurodegenerative diseases, cardiovascular diseases, type 2 diabetes, obesity, and other conditions. In the aging process, the increase in reactive oxygen species and the decrease in antioxidant pathways damage cellular components, accelerating deterioration. Persistent inflammation and oxidative stress also favor the progression of diseases such as atherosclerosis, where LDL oxidation and infiltration in the arteries generate plaques that can lead to myocardial infarction or stroke. In addition, inflammation and oxidative stress can affect the immune system, as well as the development of chronic inflammatory diseases and nonalcoholic fatty liver disease, and may affect mental health, healthy menopause and muscle recovery. Research from both human studies and laboratory tests indicates that taking 80–320 mg per day of anthocyanin-rich extracts from bilberries and blackcurrants (Anthocyanin-EBB) can moderately enhance cholesterol levels, lower markers of inflammation, boost blood vessel health, increase insulin responsiveness, and reduce indicators linked to cardiovascular and metabolic risks. They also have antioxidant, anti-inflammatory and neuroprotective effects, helping in the prevention and management of chronic diseases. As a result, supplementation with anthocyanin-rich extracts may be a promising strategy to promote healthy aging and reduce the risk of development and progression of conditions related to oxidative stress and chronic inflammation. Nevertheless, due to the limited patient populations and short follow-up periods in most existing studies, long-term clinical trials are necessary to determine the definitive advantages of Anthocyanin-EBB in clinical practice. Full article

Background: Human immunodeficiency virus (HIV) and antiretroviral therapy (ART) are known to be involved in cardiovascular disease development. They act alongside systemic risk factors, which interact with both macrovascular and microvascular vessels to accelerate vascular damage. Therefore, the aim of this study was to investigate the cardiovascular risk factors and their relationship with retinal microvascular function in HIV-positive pregnant women on ART in Mthatha, South Africa. Methods: A cross-sectional study was carried out among 78 pregnant women (25 HIV-positive and 53 HIV-negative) in Mthatha, South Africa. Blood pressure (BP) parameters, including systolic BP (SBP), diastolic BP (DBP), and heart rate (HR), were measured, and mean arterial pressure (MAP) was calculated. Lipid profile parameters and fasting blood glucose were assessed. Markers for kidney function, such as albuminuria, were determined. Vascular biomarkers including asymmetric dimethyl arginine (ADMA) and human endothelial specific molecule-1 were quantified. Non-invasive vascular function parameters such as flow-mediated slowing (FMS), carotid-femoral pulse wave velocity (cfPWV), ankle-brachial index, central retinal arteriolar equivalent (CRAE), central retinal venular equivalent (CRVE), arteriolar venular ratio (AVR), uterine artery pulsatile index (UtA PI) were determined. Results: Diastolic BP, MAP, cfPWV, ADMA, low density lipoprotein (LDL-c) and UtA PI were higher in the HIV-positive group (p ≤ 0.05) compared to the HIV-negative group. The prevalence of prehypertension/hypertension was higher in the HIV-positive group (p ≤ 0.05). DBP, MAP, and cfPWV correlated positively with CRVE in the HIV-positive group (p ≤ 0.05), while AVR negatively correlated with the urinary creatinine (uCr) in the same group (p ≤ 0.05). Linear regression results demonstrated that DBP, cfPWV, ABI, and LDL-c were predictors of reduced AVR in the HIV-positive group. Conclusions: Increased cardiovascular risk was observed in HIV-positive pregnant women on ART. Further, increased cardiovascular risk such as hypertension and endothelial dysfunction due to ART predicted retinal microvascular dysfunction in the HIV-positive population. This implies a potential mechanistic link between macrovascular dysfunction due to cardiovascular risk factors and retinal microvascular impairment, highlighting the importance of assessing cardiovascular risk early and preserving overall vascular health in HIV-positive population. Full article

Diabetic retinopathy (DR) is a progressive retinal disorder and a leading cause of vision impairment worldwide affecting the livelihood of millions. Its pathogenesis is driven by chronic hyperglycemia-induced neuronal and microvascular injury, leading to capillary occlusion, increased vascular permeability, and the eventual formation of fragile neo vessels. These changes mark the progression from non-proliferative diabetic retinopathy (NPDR) to proliferative diabetic retinopathy (PDR). Diabetic macular edema (DME), characterized by blood–retinal barrier disruption and macular fluid accumulation, further contributes to vision loss. This review provides an integrative perspective on the cellular and molecular mechanisms of DR, highlighting both vascular and neuroglial contributions to retinal pathology. Current therapeutic approaches, including anti-VEGF agents and corticosteroids, offer symptomatic relief but are limited by the need for repeated administration and variability in patient response. Emerging evidence implicates the role of thioredoxin-interacting protein (TXNIP) as one of mediators of the disease progression. Strongly upregulated under hyperglycaemic stress, TXNIP induces oxidative damage, inflammation, and neuronal apoptosis, exacerbating neurovascular dysfunction. We explore potential therapeutic strategies such as gene therapy, TXNIP-targeted molecular interventions, and stem cell-based approaches aimed at achieving long-term modulation of disease mechanisms. This article thus attempts to address a comprehensive understanding of DR pathophysiology and innovative new strategies to improve long-term visual outcomes. Full article