Search Results (263)

This story began half a century ago with the discovery of an unusually high presence of tryptophan (Trp, W) in transthyretin (TTR), one of the three carrier proteins of thyroid hormones. With the Trp-rich retinol-binding protein (RBP), TTR forms a plasma complex implicated in the delivery of retinoid compounds to body tissues. W has the lowest concentration among all AAs involved in the sequencing of human body proteins. The present review proposes molecular maps focusing on the ratio of W/AA residues found in the sequence of proteins involved in immune events, allowing us to ascribe the guidance of inflammatory processes as fully under the influence of W. Under the control of cytokine stimulation, plasma biomarkers of protein nutritional status work in concert with major acute-phase reactants (APRs) and with carrier proteins to release, in a free and active form, their W and hormonal ligands, interacting to generate hot spots affecting the course of acute stress disorders. The prognostic inflammatory and nutritional index (PINI) scoring formula contributes to identifying the respective roles played by each of the components prevailing during the progression of the disease. Glucagon demonstrates ambivalent properties, remaining passive under steady-state conditions while displaying stronger effects after cytokine activation. In developing countries, inappropriate weaning periods lead to toddlers eating W-deficient cereals as a staple, causing a dramatic reduction in the levels of W-rich biomarkers in plasma, constituting a novel nutritional deficiency at the global scale. Appropriate counseling should be set up using W implementations to cover the weaning period and extended until school age. In adult and elderly subjects, the helpful immune protections provided by W may be hindered by the surge in harmful catabolites with the occurrence of chronic complications, which can have a significant public health impact but lack the uncontrolled surges in PINI observed in young infants and teenagers. Biomarkers of neurodegenerative and neoplastic disorders measured in elderly patients indicate the slow-moving elevation of APRs due to rampant degradation processes. Full article

Background/Objectives: The aim was to identify patterns of autonomic and neuroendocrine reactivity to an immersive virtual reality (VR) social-emotional stressor and explore their associations with perceived stress and eating behavior. Methods: This one-group pretest–posttest study included 30 children and adolescents with obesity (15 boys and 15 girls), aged 8 to 17 years. The VR protocol consisted of two consecutive phases: a 5 min relaxation phase using the Forest application and a 5 min stimulation phase using a cognitively engaging VR game designed to elicit social-emotional stress. Physiological responses were measured using heart rate variability (HRV) indices and salivary stress biomarkers, including cortisol and alpha amylase. Subjective stress and eating responses were assessed via visual analogue scales (VAS) administered immediately post-exposure. The Three-Factor Eating Questionnaire (TFEQ-R21C) was used to evaluate cognitive restraint (CR), uncontrolled eating (UE), and emotional eating (EE). Results: The cortisol reactivity was blunted and may reflect both the attenuated HPA axis responsiveness characteristic of pediatric obesity and the moderate psychological challenge of the VR stressor used in this study. Two distinct autonomic response patterns were identified via exploratory factor analysis: (1) parasympathetic reactivity, associated with increased RMSSD and SDNN and decreased LF/HF, and (2) sympathetic activation, associated with increased heart rate and alpha-amylase levels and reduced RR intervals. Parasympathetic reactivity was correlated with lower perceived stress and anxiety, but also paradoxically with higher uncontrolled eating (UE). In contrast, sympathetic activation was associated with greater cognitive restraint (CR) and higher anxiety ratings. Conclusions: This study demonstrates that immersive VR game exposure elicits measurable autonomic and subjective stress responses in children and adolescents with obesity, and that individual differences in physiological reactivity are relevantly associated with eating behavior traits. The findings suggest that parasympathetic and sympathetic profiles may represent distinct behavioral patterns with implications for targeted intervention. Full article

Intimal hyperplasia (IH) compromises the patency of arteriovenous fistula (AVF) vascular access in patients with end-stage kidney disease. Uncontrolled cell proliferation and migration, driven by inflammation, shear stress and surgery, are well-known triggers in IH. Recently, microRNAs (miRNAs) have emerged as regulators of core mechanisms in cardiovascular diseases and as potential markers of IH. This study was aimed at identifying a specific miRNA panel in failed AVFs and clarifying the miRNA involvement in IH. miRNA profiling performed in tissues from patients with IH (AVFs) and normal veins (NVs) highlighted a subset of four miRNAs significantly deregulated (hsa-miR-155-5p, hsa-miR-449a-5p, hsa-miR-29c-3p, hsa-miR-194-5p) between the two groups. These miRNAs were analyzed in tissue-derived cells (NVCs and AVFCs), human aortic smooth muscle cells (HAOSMCs) and human umbilical vein endothelial cells (HUVECs). The panel of hsa-miR-449a-5p, hsa-miR-155-5p, hsa-miR-29c-3p and hsa-miR-194-5p was up-regulated in AVFCs, HAOSMCs and HUVEC under inflammatory stimuli. Notably, overexpression of hsa-miR-449a-5p exacerbated the proliferative, migratory and inflammatory features of AVFCs. In vitro pharmacological modulation of these miRNAs with pioglitazone, particularly the down-regulation of hsa-miR-155-5p and hsa-miR-29c-3p, suggested their involvement in IH pathogenesis and a potential translational application. Overall, these findings provide new insights into the pathogenesis of AVF failure, reinforcing the miRNA contribution to IH detection and prevention. Full article

Background and Objective: Intervertebral disc degeneration (IVDD) is a leading cause of lower back pain with limited regenerative treatments. Among emerging regenerative approaches, growth factor-based therapies, such as recombinant human transforming growth factor-beta (Rh-TGF-β), have shown potential for disc regeneration but are hindered by rapid degradation and uncontrolled release by direct administration. Additionally, mechanical stress elevates heat shock protein 90 (HSP-90), impairing cell function and extracellular matrix (ECM) production. This study aimed to investigate a dual self-cross-linked alginate di-aldehyde (ADA) hydrogel system for the sustained delivery of Rh-TGF-β and epigallocatechin gallate (EGCG) to enhance protein stability, regulate release, and promote disc regeneration by targeting both regenerative and stress-response pathways. Methods: ELISA and UV-Vis spectrophotometry assessed Rh-TGF-β and EGCG release profiles. A rat tail IVDD model was established with an Ilizarov-type external fixator for loading, followed by hydrogel treatment with or without bioactive agents. Disc height, tissue structure, and protein expression were evaluated via radiography, histological staining, immunohistochemistry, and Western blotting. Results: The hydrogel demonstrated a biphasic release profile with 100% Rh-TGF-β released over 60 days and complete EGCG release achieved within 15 days. Treated groups showed improved disc height, structural integrity, and proteoglycan retention revealed by histological analysis and elevated HSP-90 expression by immunohistochemistry. In contrast, Western blot analysis confirmed that EGCG effectively downregulated HSP-90 expression, suggesting a reduction in mechanical stress-induced degeneration. Conclusions: ADA hydrogel effectively delivers therapeutic agents, offering a promising strategy for IVDD treatment. Full article

Lost circulation is a major challenge in oil and gas drilling operations, severely restricting drilling efficiency and compromising operational safety. Conventional bridging and plugging materials rely on precise particle-to-fracture size matching, resulting in low success rates. Self-healing gels penetrate loss zones as discrete particles that progressively swell, accumulate, and self-repair in integrated gel masses to effectively seal fracture networks. Self-healing gels effectively overcome the shortcomings of traditional bridging agents including poor adaptability to fractures, uncontrollable gel formation of conventional downhole crosslinking gels, and the low strength of conventional pre-crosslinked gels. This work employs stearyl methacrylate (SMA) as a hydrophobic monomer, acrylamide (AM) and acrylic acid (AA) as hydrophilic monomers, and graphene oxide (GO) as an inorganic dopant to develop a GO-based self-healing organic–inorganic hybrid plugging material (SG gel). The results demonstrate that the incorporation of GO significantly enhances the material’s mechanical and rheological properties, with the SG-1.5 gel exhibiting a rheological strength of 3750 Pa and a tensile fracture stress of 27.1 kPa. GO enhances the crosslinking density of the gel network through physical crosslinking interactions, thereby improving thermal stability and reducing the swelling ratio of the gel. Under conditions of 120 °C and 6 MPa, SG-1.5 gel demonstrated a fluid loss volume of only 34.6 mL in 60–80-mesh sand bed tests. This gel achieves self-healing within fractures through dynamic hydrophobic associations and GO-enabled physical crosslinking interactions, forming a compact plugging layer. It provides an efficient solution for lost circulation control in drilling fluids. Full article

DNA is inherently unstable and is susceptible to damage from both endogenous sources (such as reactive oxygen species) and exogenous factors (including UV, ionizing radiation, and chemicals). The accumulation of DNA damage manifests as genetic mutations, chromosomal instability, and the stalling of DNA replication and transcription processes. Accumulated DNA damage influences apoptosis and cell cycle checkpoints, serving as one of the key triggers for the manifestation of the senescent phenotype. Both aging and cancer are associated with the accumulation of mutations in somatic cells. Disruption of cell cycle control and uncontrolled proliferation are fundamental characteristics of any cancer cell, with the majority of anticancer drugs acting as inhibitors of cyclin-dependent kinases, thereby inducing a transition of cells into a senescent state. Consequently, disturbances in the dynamics and regulation of inflammatory responses, oxidative stress, cell proliferation, DNA damage repair, and epigenetic anomalies, along with the influence of retroviruses and transposons, lead to the accumulation of senescent cells within the human body, characterized by blocked replication and cell cycle, as well as a distinct secretory phenotype. The age-related or disease-associated accumulation of these senescent cells significantly alters the physiology of tissues and the organism as a whole. Many secondary metabolites of higher plants exhibit senolytic and senomorphic activities, although most of them are not fully characterized. In this review, we will explore the principal signaling pathways in mammalian cells that govern the cell cycle and cellular senescence, with a particular emphasis on how their dynamics, expression, and regulation have been modified through the application of senotherapeutic compounds. The second section of the review will identify key target genes for the metabolic engineering, primarily aimed at enhancing the accumulation of plant secondary metabolites with potential therapeutic benefits. Lastly, we will discuss the rationale for utilizing liver cells as a model system to investigate the effects of senolytic compounds on human physiology and health, as well as how senotherapeutic substances can be leveraged to improve gene therapy approaches based on CRISPR/Cas9 and prime-editing technologies. Full article

Background. The venom of Loxoscelesrufescens (L.r.), also known as the violin and/or brown spider, contains a wide variety of proteins and can induce a complex, intense, and uncontrolled inflammatory response, hemolysis, thrombocytopenia, dermo-necrosis, and renal failure. Studies have postulated the efficacy of hyperbaric oxygen therapy (HBOT) for Loxosceles bites. However, data describing the use and beneficial effects of HBO are, to date, relatively scarce. Only a few cases of Loxosceles bites in Northern Italy have been documented, and there is no laboratory test available for the diagnosis. Objectives. We present seven cases (aged 54.5 ± 4.2 years) of patients who presented to the emergency room (E.R.) of Niguarda Hospital in Milan from March to October 2022. Methods. Blood and urine samples were collected and biomarkers of oxidative stress (OxS) (reactive oxygen species (ROS), total antioxidant capacity (TAC), lipid peroxidation (8iso-PFG2α), DNA damage (8-OH-dG)), inflammation (IL-6, IL-1β, TNF-α, sICAM1), and renal function (creatinine, neopterin, uric acid) before (T0), during (T1, T2), and after (1–2 wk T3–T4; 1 month T5) the HBOT treatment (US Navy Treatment Table 15 protocol) were studied. Results. At T0, patients showed a significant unbalance of OxS; high levels of ROS, 8-isoPGF2α, and inflammatory status (IL-6, TNF-α; sICAM); and a low level of antioxidant capacity. At the end of HBOT (T2), a significant reduction in Oxy-inflammation levels over time—8-iso −26%, 8-OH-dG −9%, IL-6 −71%, IL-1bβ −12%, TNF-α −13%, and sICAM1 −17%—associated with clinical improvement was shown. Conclusions. These reductions, along with those in renal function markers, mirrored the observed improvement in the evolution of the skin lesion and the patients’ self-reported general wellness and pain. In conclusion, HBOT should be considered a valuable therapeutic tool after L.r. bites. Full article

Introduction: Urinary incontinence (UI) is associated with uncontrolled urine leakage and is treated as a serious disability that prevents the fulfillment of life roles and negatively affects quality of life. Many women do not have knowledge about the nature of UI and treatment options, and the embarrassing nature of the disease makes it difficult to seek specialist care. The aim of this study was to assess quality of life among women with UI and how it affects various areas of their daily functioning. Defining factors that modify the impact of UI on quality of life can provide prognostic information about functional limitations, which will facilitate the rapid implementation of preventive and therapeutic measures. Methods: This study included 158 women with UI. Patients were asked to complete a set of questionnaires, including the Questionnaire for Urinary Incontinence Diagnosis (QUID), Revised Urinary Incontinence Scale (RUIS), King’s Health Questionnaire (KHQ), Acceptance of Illness Scale (AIS), Inventory for Measuring Coping with Stress (Mini-COPY), and Set of Scales for Self-Assessment of the relationship with a partner. Results: Based on the analyses, it was determined that women with MUI experienced a lower quality of life, greater limitations in daily activities, and greater physical limitations compared to women with UUI and SUI. There was a correlation between the severity of UI, the duration of the disease, the level of acceptance of the disease, the education level of the subjects, and quality of life in all areas of functioning. Conclusions: Numerous functional limitations and reduced quality of life have been observed among patients with UI. As part of UI management in clinical practice, it seems reasonable to include measures aimed at identifying patients who are likely to experience more severe consequences of UI so that they can receive targeted care. Full article

Face recognition systems often falter when deployed in uncontrolled settings, grappling with low light, unexpected occlusions, motion blur, and the degradation of sensor signals. Most contemporary algorithms chase raw accuracy yet overlook the pragmatic need for uncertainty estimation and multispectral reasoning rolled into a single framework. This study introduces HUE-Net—a Human-centric, Uncertainty-aware, Event-fused Network—designed specifically to thrive under severe environmental stress. HUE-Net marries the visible RGB band with near-infrared (NIR) imagery and high-temporal-event data through an early-fusion pipeline, proven more responsive than serial approaches. A custom hybrid backbone that couples convolutional networks with transformers keeps the model nimble enough for edge devices. Central to the architecture is the perturbed multi-branch variational module, which distills probabilistic identity embeddings while delivering calibrated confidence scores. Complementing this, an Adaptive Spectral Attention mechanism dynamically reweights each stream to amplify the most reliable facial features in real time. Unlike previous efforts that compartmentalize uncertainty handling, spectral blending, or computational thrift, HUE-Net unites all three in a lightweight package. Benchmarks on the IJB-C and N-SpectralFace datasets illustrate that the system not only secures state-of-the-art accuracy but also exhibits unmatched spectral robustness and reliable probability calibration. The results indicate that HUE-Net is well-positioned for forensic missions and humanitarian scenarios where trustworthy identification cannot be deferred. Full article

This paper employs direct numerical simulation (DNS) to investigate the influence of blowing and suction control on the compressible fully developed turbulent flow within an infinitely long channel. The spanwise blowing strips are positioned at uniform intervals along the bottom wall of the channel, while the suction strips are symmetrically placed on the top wall. The basic flow (uncontrolled case) and the controlled cases involving global control and interval control are compared at $Ma=0.8$ and 1.5. Although the wall mass flow rate remains constant across all controlled cases, the applied blowing/suction intensity and spanwise strip areas exhibit significant variations. The numerical results indicate that augmenting the blowing/suction intensity will alter the velocity gradient of the viscous sublayer in the controlled region. Nonetheless, a reduction in the area of the controlled region diminishes the impact of blowing/suction on drag reduction on the entire wall. The spatially averaged velocity profiles on the wall for cases with identical wall mass flow rates are nearly indistinguishable, suggesting that the wall mass flow rate is the primary factor influencing the spatially averaged drag reduction rate on the entire wall, rather than the blowing/suction intensity or the injected energy. This is because the wall mass flow rate influences the average peak position of the Reynolds stress, which, in turn, affects the skin friction drag. An increase in the wall mass flow rate correlates with a heightened drag reduction rate on the blowing side, while simultaneously leading to a rising drag increase rate on the suction side. Full article

Preterm premature rupture of membranes (pPROM) is a leading cause of preterm birth (PTB) and is increasingly recognized for its association with neurodevelopmental disorders (NDDs). The disruption of fetal membrane integrity introduces potential infection and inflammation into the intrauterine environment, triggering immune responses that may affect fetal development. Placental inflammation plays a pivotal role in mediating these effects, exposing the fetus to cytokines, oxidative stress, and potential microbial insults that contribute to adverse neurodevelopmental outcomes. This review examines the current evidence of the mechanistic pathways linking pPROM-induced placental inflammation to NDDs, emphasizing the roles of pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) in the inflammatory responses. We discuss how these immune activations lead to immune cell recruitment and excessive (or uncontrolled) production of inflammatory mediators, leading to an overall inflammatory imbalance that has been linked to disrupted fetal brain development in animal models. Animal models provide critical insights into how both sterile and pathogenic placental inflammation alter fetal neurodevelopment, while human studies, though limited, highlight promising biomarkers and potential therapeutic targets. This review identifies critical knowledge gaps and outlines future directions to mitigate the impact of placental inflammation on long-term infant health. Full article

The final recipient of nanoparticles, including various types of copper-based nanoparticles (Cu-based NPs), is the aquatic environment. Their increased production, especially as a component of antimicrobial agents, raises concerns about uncontrolled environmental release and subsequent ecological risks. The high reactivity of Cu-based NPs enables interactions with biotic and abiotic environmental components, leading to bioaccumulation and disorders in living organisms, such as fish in various life stages, especially in embryos or hatchlings. Increasing concentration of Cu-based NPs causes various toxic effects, mainly through the induction of oxidative stress. These effects include impairment of antioxidant mechanisms, as well as damage to genetic material, cells and tissues, growth retardation, metabolic disorders, increased mortality, or hatching inhibition. The aim of this review is to describe the release routes of Cu-based NPs and their adverse effects on fish, while emphasizing the need for further research on their toxicity and measures to control their release to the environment. Given the limited data on the toxicity of Cu-based NPs, especially concerning sensitive fish developmental stages, further studies are required. Full article

The nucleoprotein structures known as telomeres provide genomic integrity by protecting the ends of chromosomes. Tumorigenesis is associated with alterations in telomere function and stability. This narrative review provides evidence of the potential prognostic value of telomere length and telomerase in leukemias. On the one hand, oxidative stress and mitochondrial dysfunction can accelerate telomere shortening, leading to higher susceptibility and the progression of leukemia. On the other hand, cytogenetic alterations (such as gene fusions and chromosomal abnormalities) and genomic complexity can result from checkpoint dysregulation, the induction of the DNA damage response (DDR), and defective repair signaling at telomeres. This review thoroughly outlines the ways by which telomere dysfunction can play a key role in the development and progression of four primary leukemias, including chronic lymphocytic leukemia (CLL), chronic myeloid leukemia (CML), and acute leukemias of myeloid or lymphoid origin, highlighting the potential prognostic value of telomere length in this field. However, telomerase, which is highly active in leukemias, can prevent the rate of telomere attrition. In line with this, leukemia cells can proliferate, suggesting telomerase as a promising therapeutic target in leukemias. For this reason, telomerase-based immunotherapy is analyzed in the fight against leukemias, leveraging the immune system to eliminate leukemia cells with uncontrolled proliferation. Full article

Fire is a distinctive factor in forest ecosystems. While uncontrolled wildfires can cause significant damage, prescribed burning is widely used as a management tool. However, despite the growing threat of forest water stress under climate change, there is a lack of concrete evidence on the impact of fire on water stress in forest ecosystems. This study utilized Landsat time-series remote sensing data combined with the Infrared Canopy Dryness Index (ICDI) to monitor changes in canopy dryness patterns across the eucalyptus-dominated Northern Jarrah Forest of southwestern Australia. The forest was chosen due to its exposure to a changing climate characterized by decreasing rainfall and more frequent droughts, signs of water stress in otherwise drought-resilient trees, and its well-documented fire management history. Analysis of ICDI patterns over the period from 1988 to 2024 revealed a clear overall trend of increasing water stress, coinciding with a small overall decline in annual rainfall in the 10,000 km² study area. Furthermore, by examining five prescribed burns and five wildfires, we found that NDVI-assessed canopy cover recovered rapidly in fire-affected areas, typically within one to three years, depending on fire severity. However, ICDI water stress levels were reduced for approximately 7–8 years following low-severity prescribed burns and more than 20 years after high-severity wildfires. These findings suggest the potential of prescribed burning as a tool to mitigate water stress in vulnerable forest landscapes, particularly in regions prone to drought and climate change. Additionally, the study underscores the effectiveness of the ICDI in monitoring forest water stress and its potential for broader applications in forest management and climate adaptation strategies. Full article

Background: Asthma is a chronic inflammatory airway disease in which oxidative stress and antioxidant imbalance play a critical role in disease progression and therapeutic response. This study aimed to evaluate oxidative stress and antioxidant status in relation to asthma control levels. Methods: A total of 106 patients admitted to the Clinical Hospital of Pulmonary Diseases, Iași, between March and May 2024 were included in this study. Patients were classified into three groups based on asthma control: well-controlled (AB-TCG), partially controlled (AB-PCG), and uncontrolled asthma (AB-UCG). Demographic, biochemical, and hematological parameters were assessed, with attention to oxidative stress markers and antioxidant defenses. Results: The study population was predominantly female (75%), with a mean age ranging from 50.75 to 64.38 years, and the majority residing in rural areas (73–75%). The AB-UCG group showed significantly elevated inflammatory markers, including a white blood cell count of 9.33 × 10³/µL (p = 0.005) and eosinophil percentage of 4.20% (p = 0.03), compared with the other groups. This group also exhibited an unfavorable lipid profile, with increased total cholesterol (207.40 mg/dL) and triglyceride levels (157.21 mg/dL). Oxidative stress was notably higher in the AB-UCG group, as indicated by elevated malondialdehyde (MDA) levels (2.86 mmol/L) versus 2.35 mmol/L in the AB-PCG group (p < 0.005), along with decreased serum uric acid (4.64 mg/dL) and reduced glutathione (GSH) levels (275.41 µmol/L), leading to a lower GSH/GSSG ratio. Environmental exposures, including tobacco smoke and occupational chemicals, were associated with exacerbated oxidative imbalance. Conclusions: The findings highlight the critical involvement of oxidative stress and compromised antioxidant defenses in poorly controlled asthma. Biomarkers such as MDA, white blood cell count, eosinophil percentage, and the GSH/GSSG ratio may act as valuable tools for personalized asthma management and therapeutic monitoring. Full article