Search Results (224)

Retinal neurovascular unit (RNVU) dysfunction underlies major blinding and neurodegenerative conditions including glaucoma, diabetic retinopathy (DR), age-related macular degeneration (AMD), retinal ischemia–reperfusion (RIR) injury, and Alzheimer’s disease (AD)-associated retinopathy. Within the RNVU, calcium ions coordinate neurotransmission, glial activation, vascular tone, and blood–retinal barrier maintenance, and calcium dysregulation is emerging as a unifying pathogenic hub across these conditions. Although upstream triggers differ, including mechanical stress in glaucoma, hyperglycemia in DR, oxidative damage in AMD, ischemic energy failure in RIR, and amyloid-β–driven endoplasmic reticulum stress in AD, all converge on disruption of intracellular calcium homeostasis, producing shared downstream consequences including excitotoxic injury of retinal ganglion cells (RGCs), Müller cell reactive gliosis, and pericyte hypercontraction. Broad-spectrum calcium channel blockade has shown limited clinical success, underscoring the need for cell-type-specific and pathway-selective approaches. This review therefore catalogs key interventional nodes, including transient receptor potential (TRP) channel antagonists, T-type calcium channel inhibitors, calcium/calmodulin-dependent protein kinase II (CaMKII) suppressors, and mitochondrial permeability transition pore (mPTP) inhibitors, and discusses how precision targeting of these pathways may restore RNVU homeostasis and open a therapeutic window into central nervous system (CNS) degenerative disorders. Full article

Ophicarbonates provide an important natural record of mineral carbonation during serpentinization of ultramafic rocks and therefore offer insight into the mechanisms and limits of CO₂ fixation in low-temperature geological environments. This paper presents a synthesis and process-oriented reinterpretation of stable-isotope published and previously unpublished data, petrographic, and mineralogical evidence for carbonate formation under fluid-limited serpentinization conditions. Using mineralogical constraints together with a compiled δ¹³C–δ¹⁸O dataset that includes legacy measurements from the 1980s–1990s, we evaluate how multi-stage carbonate precipitation reflects evolving water–rock ratio, redox state, transport limitation, and deformation-controlled permeability. Particular attention is given to systematic differences between vein-hosted carbonates and dispersed intergranular or scattered-grain ophicarbonates, as these textural–isotopic relationships help identify fluid flux, carbon source, and reaction progress in ultramafic systems. The analysis shows that carbonation does not proceed uniformly but is restricted to overlapping reactive windows controlled by fluid availability, nucleation kinetics, and permeability evolution. These constraints help explain why carbonation may either intensify or stall during progressive serpentinization. The Author further discuss why kinetic barriers and Mg–Ca partitioning may redirect carbonate mineralogy toward calcite or metastable Mg-rich phases even where dolomite or magnesite may be thermodynamically favored. The results highlight the importance of coupling isotopic signatures with petrographic context in reconstructing carbonation pathways and provide a broader framework for understanding natural mineral sequestration of carbon in heterogeneous serpentinite systems. Full article

Electrokinetic-Permeable Reactive Barrier (EK-PRB) technology can effectively remediate heavy metal-contaminated soil, and the properties of PRB materials play an important role in determining the remediation efficiency. To select a suitable PRB material, montmorillonite (MMT) was modified using cetyltrimethylammonium bromide (CTAB), sodium dodecylbenzenesulfonate (SDBS), and cocamidopropyl betaine (CAB), respectively; their remediation efficiencies for soils co-contaminated with Zn²⁺, Pb²⁺, and Cd²⁺ were then compared within an EK-PRB system. The results indicated that remediation efficacy varied significantly depending on the heavy metal and the surfactant used for modification. After 7 days of remediation, SDBS-modified MMT achieved the highest Zn²⁺ removal efficiency (49.65%), whereas CTAB-modified MMT showed optimal removal performance for both Pb²⁺ (38.03%) and Cd²⁺ (76.02%). When the remediation time was extended to 14 days, SDBS-modified MMT attained the highest removal efficiencies for Zn²⁺ (69.80%) and Pb²⁺ (69.50%), while CTAB-modified MMT maintained superior Cd²⁺ removal performance (86.94%). Energy consumption analysis showed that both CAB- and SDBS-modified MMT reduced energy consumption moderately compared with the unmodified control, whereas CTAB modification resulted in a substantial increase in energy demand. Experimental results confirm that surfactant-modified MMT effectively optimizes the EK-PRB remediation. A comprehensive evaluation considering both removal efficiency and energy consumption identified SDBS-MMT as the optimal material. The optimized EK-PRB parameters established in this study provide theoretical and technical support for the remediation of soils co-contaminated with multiple heavy metals. Full article

Global water pollution driven by industrial and agricultural expansion has resulted in the widespread occurrence of persistent contaminants, particularly pharmaceuticals and heavy metals, in groundwater systems. Conventional treatment methods often prove inefficient, costly, and environmentally unsustainable, highlighting the need for innovative in situ remediation technologies. Permeable Reactive Barriers (PRBs) have emerged as a promising and energy-efficient solution for the long-term purification of contaminated aquifers. Their efficiency arises from passive operation, relying on natural groundwater flow to promote pollutant removal through adsorption, ion exchange, precipitation, and redox-driven transformations. This review emphasizes the superior performance of materials such as Activated Carbon, Biochar, Zeolites, and Zero-Valent Iron (ZVI) in the immobilization and reduction in pharmaceuticals and metal ions. Key challenges to PRB longevity include permeability loss and reactive media depletion due to mineral precipitation and biofouling. Advances in hybrid PRB configurations, coupled with electrokinetic (EK) and bioreactor systems, and predictive modeling, particularly Artificial Neural Networks (ANNs), offer pathways to enhance performance, optimize design, and ensure sustainable operation. Overall, PRBs represent a scalable and environmentally sound approach to groundwater remediation, with future progress relying on the development of multifunctional, regenerable materials and integrated design strategies. Full article

Background: Chronic stress is a major risk factor for cognitive decline and blood–brain barrier (BBB) disruption, yet the underlying molecular mechanisms remain elusive. This study aimed to investigate the specific role of the metabolic intermediate homocysteine (Hcy) in chronic stress-induced BBB dysfunction and cognitive impairment. Methods: We utilized a male Sprague-Dawley rat model of chronic unpredictable mild stress (CUMS) and administered vitamin B complex to lower Hcy levels in vivo. Regional Hcy accumulation, BBB permeability, and cognitive behaviors were assessed. In vitro, primary rat brain microvascular endothelial cells (BMECs) were exposed to Hcy to evaluate barrier-forming function, transcriptomic alterations, DNA methylation patterns, Cav1.2 expression, and reactive oxygen species (ROS) production. Results: CUMS selectively induced BBB hyperpermeability and significant Hcy accumulation predominantly within the rat hippocampus, which correlated intimately with cognitive deficits. Lowering Hcy levels via vitamin B supplementation successfully restored hippocampal BBB integrity and alleviated cognitive impairment. In addition, elevated Hcy severely impaired the barrier function of BMECs. Mechanistically, Hcy reduced global DNA methylation in BMECs and specifically induced targeted DNA hypomethylation at the intro region of Cacna1c. This epigenetic shift caused the transcriptional derepression and overexpression of the Cav1.2 calcium channel. Upregulated Cav1.2 subsequently triggered a robust ROS burst, leading to tight junction degradation. Conclusions: Our findings unveil a novel metabolic–epigenetic axis where Hcy-driven Cacna1c hypomethylation directly disrupts BMECs function to dismantle the hippocampal BBB. Lowering Hcy or targeting this Hcy-Cav1.2 pathway establishes a promising therapeutic strategy for mitigating stress-related neurovascular damage and cognitive disorders. Full article

Metabolic diseases are strongly associated with chronic systemic inflammation and oxidative stress, which disrupt the microbiota–gut–brain (MGB) axis and promote neuroinflammation. Dysbiosis favors the release of proinflammatory metabolites, reactive oxygen species (ROS), and lipopolysaccharides (LPS), increasing intestinal permeability and triggering systemic immune responses that reach the central nervous system (CNS) through a weakened blood–brain barrier (BBB). This review summarizes current knowledge on the pathophysiological mechanisms linking the MGB axis, metabolic disorders, and neuroinflammation, as well as the therapeutic potential of antioxidants. A literature search was conducted in PubMed, Web of Science, Scopus, and ScienceDirect and included original research articles, reviews, clinical trials, and meta-analyses related to microbiota, neuroinflammation, oxidative stress, and antioxidant interventions. Evidence indicates that dysbiosis exacerbates metabolic dysfunction by activating the nuclear factor kappa B (NF-κB) and NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome pathways, while excessive ROS production impairs mitochondrial function, neuronal survival, and cognitive processes. Antioxidant strategies, including polyphenols, omega-3 fatty acids, curcumin, vitamins C and E, and probiotics, can restore microbial diversity, reinforce intestinal and BBB integrity, and modulate oxidative and inflammatory signaling. In conclusion, supplements and bacteria with antioxidant properties show promising therapeutic effects by targeting oxidative stress mechanisms involved in metabolic diseases and their pathological consequences, such as dysbiosis and neuroinflammation. Full article

Diffuse pollution from agricultural runoff, characterized by intermittent discharges of complex contaminant mixtures, including nutrients, pesticides, and heavy metals (HMs), poses a persistent threat to global water quality. Conventional “end-of-pipe” strategies often fail to address these decentralized, nonpoint sources. This review examines the evolution of Permeable Reactive Barriers (PRBs) from static, abiotic filters into modern Permeable Reactive Bio-Barriers (PRBBs), engineered as dynamic, fixed-bed biofilm reactors. A key advancement in PRBB efficacy is the exploitation of biofilm plasticity, particularly in response to coexistence with organic and inorganic pollutants. While heavy metals are traditionally viewed as inhibitors, this review synthesizes evidence showing that subinhibitory HM levels can act as structural and functional drivers. These metals induce the upregulation of Extracellular Polymeric Substances (EPSs), creating a “protective shield” that sequesters metals and confers functional resilience on the microbial consortia responsible for nutrient removal and pesticide biodegradation. The review analyzes contaminant removal mechanisms, highlighting the bio-chemo synergy between reactive media and biofilms, and proposes a classification framework based on target contaminants, media, and technological integration. Significant focus is placed on emerging hybrid multi-media systems designed to protect the microbial community from toxic metal shocks, alongside the integration of artificial intelligence for predictive control. While challenges in hydraulic sustainability and field validation remain, PRBBs represent a compact, low-energy, and scalable ecotechnology. PRBBs offer a strategically targeted solution within the Nature-Based Solutions toolkit for building resilient protection of aquatic ecosystems at the critical land-water interface. Full article

Permeable reactive barrier (PRB) is an in situ remediation of contaminated sites mostly suitable for halogenated pollutants like halo-hydrocarbons reduced by zero-valent irons (ZVI) developed during early 1990’s. However, remediation of some nitrogen-pollutants like ammonia and urea is unsuccessful due to lack of reactants. Most recent advanced direct ammonia/urea fuel cells utilize indirect hydrogen within ammonia/urea molecules to generate electricity. Herein, a comprehensive study based on the chosen design, working principles, advantages and disadvantages of direct ammonia fuel cells for new approach of PRBs for denitrifying nitrogen-contaminant is summarized. Most surveys are carrying out in our laboratories and this work aims to review the most recent advances in ammonia fuel cells integrated with PRBs and demonstrates the proximity of this technology to future applications. Meanwhile, several challenges such as how to accumulate ammonia and urea in order to achieve satisfying energy recovery, oxidants formation, power densities and long term stability are also summarized in this review. Full article

Ferulic acid, a derivative of hydroxycinnamic acid, is a potent antioxidant used in dermatology for its ability to neutralize reactive oxygen species and stabilize vitamins C and E. Its multidirectional action includes photoprotection, anti-inflammatory effects, and inhibition of melanogenesis. The study aimed to quantitatively evaluate the impact of 20% ferulic acid peels on skin barrier function, sebum level, pH, and biomechanical properties (elasticity). A group of 18 subjects underwent a series of three treatments. Objective skin parameters were measured. Assessments were conducted at baseline and 14 days post-treatment. A statistically significant increase in stratum corneum hydration was observed on the cheek. Barrier function improved significantly, with transepidermal water loss (TEWL) decreasing in both analyzed areas. Biomechanical analysis revealed a statistically significant improvement in elasticity (R2 parameter) on the cheek and forehead (p < 0.05). Ferulic acid has the potential to improve epidermal hydration and support the skin’s permeability barrier, as evidenced by reduced TEWL. The stability of skin pH suggests high tolerability, confirming ferulic acid as an effective therapeutic agent for mature and sensitive skin. Full article

Asthma is increasingly recognized as a heterogeneous syndrome where traditional management fails, particularly given spirometry’s limitations in assessing small airway dysfunction. This review synthesizes the transition from clinical phenotyping to deep molecular endotyping, establishing a framework for precision medicine. We highlight the insufficiency of absolute eosinophil counts, proposing eosinophil cationic protein (ECP) and eosinophil-derived neurotoxin (EDN) as superior activation metrics. Furthermore, we explore Type 2 drivers (IL-4/IL-13, periostin) and epithelial alarmins like TSLP. Beyond classical immunology, the text describes metabolic dysregulation, specifically asymmetric dimethylarginine (ADMA) in obese-asthma phenotypes where nitric oxide synthase uncoupling promotes oxidative stress. We also analyze YKL-40 and surfactant protein D (SP-D) as markers of remodeling and barrier permeability, alongside microRNAs—specifically miR-21—in corticosteroid resistance. We conclude that managing refractory asthma requires shifting from reactive symptom control to an integrated analysis of multi-omic biomarkers. Establishing this comprehensive molecular profile via specialized centers is fundamental for addressing current diagnostic limitations, selecting biological therapies, and modifying the disease trajectory through an endotype-driven strategy addressing inflammatory, metabolic, and structural pathologies. Full article

Low-saturated hydraulic conductivity covers (LSHCC) or hydraulic barriers are one of the reclamation techniques used to control the acid mine drainage generation (AMD). These covers are intended to limit the infiltration of water into reactive tailings. Compacted clays are among the materials used as LSHCC. The performance of clay-based hydraulic barriers can be affected by their geotechnical and hydrogeological properties. Freeze–thaw cycles can increase their saturated hydraulic conductivity (k_sat). However, these effects can be minimized by adding amendments. To evaluate the performance of these clay-based covers, four field experimental cells were built. The first one simulates a cover composed entirely of clay, the second a clay–silt mixture, the third a clay–sand mixture and the last two layers of clay with an intermediate layer of silt. Each cell has been equipped with a monitoring station with continuous measurements of volumetric water content, suction and temperature. In situ permeability tests were also conducted to assess field hydraulic conductivity. Numerical simulations were also conducted to evaluate the water balance for each cover scenario. The laboratory results showed low-saturated hydraulic conductivity values meeting waterproofing criteria, whereas field measurements and calibrated model values were consistently higher and exceeded the waterproofing criteria. Infiltration monitoring indicated that 15 to 40% of precipitation infiltrated the covers, with possible overestimation due to preferential flow. Discrepancies between laboratory and field-saturated hydraulic conductivity values were mainly attributed to inadequate compaction, unfavorable weather conditions, and excessive water content during cover installation. Variations in saturated hydraulic conductivity over time were generally within statistical variability, although differences among cells and responses to wetting–drying cycles highlight the influence of construction conditions on field performance. Full article

Background/Objectives: Benign prostatic hyperplasia (BPH) is a multifactorial condition associated with androgen imbalance, oxidative stress, and chronic inflammation, leading to growing interest in food-derived bioactive compounds with multitarget activity. This study aimed to investigate the biological effects of a nutraceutical combination of Gastrodiae elata Blume extract and coenzyme Q10 (Q10), focusing on mechanisms relevant to prostate physiological balance using food-relevant in vitro models. Methods: An intestinal epithelial barrier model (Caco-2) was employed to assess intestinal tolerance and permeability of the tested compounds. Subsequently, a prostate epithelial–stromal co-culture exposed to dihydrotestosterone (DHT) was used to reproduce BPH-like cellular conditions. Oxidative stress, inflammatory mediators, androgen-related pathways, and markers of proliferation and apoptosis were evaluated following simulated intestinal passage. Results: The combined formulation showed no cytotoxic effects and demonstrated efficient intestinal permeability. After intestinal passage, the combination significantly reduced oxidative stress and inflammatory responses in the prostate co-culture, decreasing reactive oxygen species and pro-inflammatory mediators, including NF-κB, TNF-α, and IL-1β. In parallel, the formulation modulated androgen-related pathways by reducing 5-α-reductase activity and DHT levels while supporting testosterone homeostasis. Across some of the evaluated endpoints, the combined formulation tended to show more pronounced protective effects compared with the individual components. Conclusions: These results suggest that a combination of Gastrodiae elata and coenzyme Q10 may have a positive effect on prostate health. In the nutraceutical field, this food-based formulation could help support prostate health, probably through antioxidant, anti-inflammatory, and hormonal control mechanisms. Further studies using advanced experimental models are warranted. Full article

A novel low-cost poly(propylene carbonate-co-epichlorohydrin) (PPC-ECH) with mechanical properties similar to those of poly (butylene adipate-co-terephthalate) (PBAT) was developed and incorporated into a poly(propylene carbonate-co-phthalate) (PPC-P) matrix. Meanwhile, 4, 4′-diphenylmethane diisocyanate (MDI) was employed as a reactive compatibilizer and mixed with PPC-P and PPC-ECH to create a variety of PPC-P/PPC-ECH/MDI blends. The effects of PPC-ECH and MDI content on the mechanical, optical, thermal, morphological, and gas barrier properties of the blends were systematically investigated. Results demonstrated that MDI reacts with both PPC-P and PPC-ECH, forming a chemically bonded interface that significantly improves their compatibility. Notably, when 2 phr of MDI was incorporated, the elongation at break of the PPC-P/PPC-ECH/2MDI blend increased dramatically from 71% to 502%, while maintaining good tensile strength (~23 MPa) and light transmittance (~80%). To further enhance the gas barrier performance, a high-oxygen-barrier poly(vinyl alcohol) (PVA)/tannic acid (TA) complex coating was applied to the surface of the PPC-P/PPC-ECH/2MDI film. This coating synergistically leveraged the abundant hydroxyl groups in PVA and TA to form a dense hydrogen-bonded network, reducing oxygen permeability to an ultra-low value of 0.1 cm³·mm/(m²·day). This outstanding performance highlights the strong potential of PPC-P/PPC-ECH-based films for advanced packaging applications. Full article

Objectives: Hypertension is common in Alzheimer’s disease (AD) and contributes to functional decline. While ACE inhibitors are widely used for hypertension, their systemic effects on intestinal permeability and physical capacity in AD patients remain unclear. Materials and Methods: We investigated the potential contribution of increased intestinal permeability to handgrip strength (HGS) and physical capacity in patients with Alzheimer’s disease (AD) taking ACE inhibitors. We investigated hypertensive AD patients taking ACE inhibitors (n = 55) or other anti-hypertensive medications (n = 57) at baseline and one year later, along with age-matched controls (n = 64) and normotensive AD patients (n = 61). We measured plasma zonulin, a marker of intestinal permeability, and HGS, and performed the short physical performance battery (SPPB). Results: AD patients had lower HGS, gait speed, SPPB, and higher plasma zonulin than controls at baseline (all p < 0.05). The use of ACE inhibitors was associated with increased HGS and gait speed, and reduced plasma zonulin in AD patients. Conversely, AD patients on other anti-hypertensive medications had higher zonulin and lower HGS but no change in gait speed and SPPB after one year. The patients taking ACE inhibitors also exhibited significant dynamic correlations of zonulin with HGS, gait speed, and SPPB (p < 0.05). ACE inhibitors also reduced plasma C-reactive proteins and 8-isoprostanes as markers of oxidative stress and inflammation. Conclusions: ACE inhibitors may improve physical performance and cognitive function in hypertensive AD patients, primarily through vascular smooth muscle modulation, leading to better perfusion. These effects may indirectly support intestinal barrier and muscle function, highlighting a novel gut–vascular–muscle interface relevant to therapeutic strategies. Full article

Oxidative stress and excitotoxicity are key contributors to neuronal damage in various neurodegenerative diseases. Caffeine, a widely used neuroactive compound with moderate antioxidant properties, may benefit from structural modifications to enhance its neuroprotective potential. In this study, a series of novel caffeine derivatives was synthesized and evaluated for antioxidant and potential neuroprotective relevance using in vitro models of oxidative stress and glutamate-induced excitotoxicity in SH-SY5Y human neuroblastoma cells. Antioxidant capacity was assessed using ABTS•⁺ radical cation decolorization and DPPH radical scavenging assays. Most derivatives exhibited strong free radical scavenging activity, surpassing both caffeine and the reference antioxidant Trolox at low concentrations (5 µM). Notably, compounds AL-7, AL-8, AL-9, and AL-10 demonstrated particularly high activity. Cytotoxicity evaluation using the MTT assay revealed low toxicity for all compounds, with calculated IC₅₀ values above 500 µM. Intracellular reactive oxygen species (ROS) levels measured by the DCFH-DA assay showed that several derivatives, especially AL-4, significantly reduced H₂O₂-induced oxidative stress. In neuroprotection assays, compounds AL-0, AL-1, and AL-4 markedly protected against hydrogen peroxide-induced damage, restoring cell viability up to 73%, while AL-7 achieved up to 85% protection against L-glutamate-induced excitotoxicity, outperforming caffeine. In silico SwissADME analysis indicated favorable oral bioavailability, with predicted gastrointestinal absorption and limited blood–brain barrier permeability. Overall, these findings highlight structurally modified caffeine derivatives as promising antioxidant and neuroprotective agents warranting further mechanistic and therapeutic investigation. Full article