Search Results (18,889)

Microplastics (MPs) are pervasive environmental contaminants detected in terrestrial, aquatic, and human systems. Emerging evidence indicates that MPs interact with microbiota through biofilm formation, induction of oxidative stress, enrichment of antibiotic resistance genes (ARGs), and disruption of short-chain fatty acid metabolism, leading to dysbiosis and altered host immune responses. These interactions contribute to dysbiosis, altered immune responses, and increased dissemination of ARGs, which pose health risks. This review synthesizes current knowledge on mechanisms of microplastic–microbiota interactions, highlighting evidence from in vitro, in vivo, and environmental studies. We discuss methodological challenges, including variability in particle types, concentrations, aging, and analytical approaches. Recent advances in multi-omics techniques provide deeper mechanistic understanding and reveal functional consequences of MP exposure. We outline key knowledge gaps and propose future research directions to assess the impact of microplastic exposure on ecosystems and human health. Full article

ERF/AP2 is a family of transcription factors that plays a broad role in plant growth and development and in responses to various environmental stresses. In our previous studies, we found that the transcription factor LoERF4 indirectly induces the breaking of dormancy in lily bulbs by regulating its downstream gene, LoXTH23. To further investigate the function of LoERF4, we overexpressed it in Arabidopsis thaliana. Paraffin section analysis revealed that root cells in OE-LoERF4 transgenic Arabidopsis thaliana lines exhibited significantly longer average cell lengths compared to the wild type. In the overexpression lines, the expression of multiple modified genes, including AtXTHs and AtEXPAs was significantly upregulated, and these lines exhibited earlier lateral root emergence and a significant increase in primary root length. Under 100 mM sodium chloride treatment, the overexpression lines exhibited significantly higher numbers of lateral roots, true leaves, and primary root length compared with the wild type (WT). In the OE-LoERF4 line, antioxidant enzyme (SOD, POD, CAT) activity was enhanced, oxidative damage was reduced (decreased MDA content), and root survival rate was improved (as reflected by TTC reduction). This confirms that LoERF4 may promote root development in the overexpression line by positively regulating downstream AtXTHs and AtEXPAs, while simultaneously enhancing the salt tolerance of the overexpression line. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a leading cause of chronic liver disease worldwide and arises from systemic metabolic dysregulation and insulin resistance. Despite its increasing prevalence, effective pharmacological interventions remain limited. Recent evidence has identified sirtuin 6 (SIRT6), an NAD⁺-dependent epigenetic regulator, as an important modulator of hepatic metabolic and stress-responsive pathways. This review summarizes current knowledge regarding the role of SIRT6 in liver physiology and MASLD pathogenesis. Accumulating evidence indicates that SIRT6 suppresses lipogenic transcriptional programs while enhancing mitochondrial oxidative capacity and fatty acid oxidation, thereby maintaining metabolic homeostasis. Beyond lipid metabolism, SIRT6 is implicated in the regulation of endoplasmic reticulum stress responses, inflammatory signaling, and chromatin accessibility, which are the processes that collectively influence hepatocellular injury and disease progression. In addition, emerging data suggest that SIRT6 modulates hepatic stellate cell activation and fibrogenic signaling pathways, thereby linking epigenetic regulation to the development of liver fibrosis. A reduction in hepatic SIRT6 expression and activity has been reported in metabolic disorders, including MASLD. We further discuss the therapeutic potential of targeting SIRT6, including the development of selective small-molecule activators and naturally derived compounds aimed at restoring SIRT6 activity. Together, the available evidence positions SIRT6 as an important regulatory node in MASLD and a promising candidate for future therapeutic intervention. Full article

Iron-based nanoparticles, particularly iron oxide nanostructures (IONPs), have emerged as versatile and clinically relevant platforms for drug delivery and theranostic applications. Among these, superparamagnetic iron oxide nanoparticles (SPIONs), including magnetite (Fe₃O₄) and maghemite (γ-Fe₂O₃), are the most extensively investigated due to their biocompatibility, magnetic responsiveness, and established safety profiles. Their unique superparamagnetic behavior enables external magnetic-field-guided targeting, magnetic resonance imaging (MRI) contrast enhancement, and magnetically triggered hyperthermia, enabling simultaneous diagnosis and therapy. Surface functionalization with polymers, silica, lipids, peptides, and biomolecules further improves colloidal stability, circulation time, targeting specificity, and controlled drug release. Core–shell architectures and multifunctional hybrid systems have expanded the therapeutic scope of iron nanoparticles, integrating chemotherapy, gene delivery, photothermal therapy, and Fenton reaction–mediated catalytic therapy. Despite promising preclinical outcomes, challenges remain regarding long-term biosafety, oxidative stress induction, biodistribution, large-scale reproducibility, and regulatory translation. This review summarizes the physicochemical properties, synthesis strategies, surface-engineering approaches, drug-loading mechanisms, and biomedical applications of iron-based nanoparticles, highlighting recent advances in multifunctional and peptide-functionalized systems. Critical considerations for clinical translation and future perspectives in precision nanomedicine are also discussed. Full article

Chronic diseases increasingly reflect a shared biological origin: persistent cellular stress. This review summarizes the biochemical mechanisms that normally preserve cellular homeostasis, namely redox regulation, endoplasmic reticulum proteostasis, mitochondrial quality control, autophagy, and DNA damage response, and explains how they fail under sustained lifestyle-related overload. Repeated exposure to psychological stress, sleep disruption, hypercaloric intake, and physical inactivity shifts adaptive signaling toward maladaptation, promoting oxidative damage, protein misfolding, mitochondrial dysfunction, low-grade inflammation, and genomic instability. These interconnected processes contribute to the development and progression of major chronic non-communicable diseases, including obesity, type 2 diabetes, cardiovascular disease, neurodegeneration, and cancer. Particular emphasis is placed on circadian and neuroendocrine regulation, especially overactivation of the hypothalamic–pituitary–adrenal axis and impaired nocturnal regenerative pathways such as glymphatic clearance and DNA repair. Together, the evidence supports a unifying model in which chronic pathology emerges from cumulative failure of cellular resilience systems rather than isolated organ-specific defects. This perspective highlights sleep optimization, stress reduction, and metabolic regulation as mechanistically grounded strategies for prevention and supportive interventions for chronic disease. Full article

Chronic Obstructive Pulmonary Disease (COPD) is characterized by persistent inflammation and structural alterations in the lung triggered mainly by oxidative stress. Colonization by the opportunistic fungus Pneumocystis has been associated with worse clinical outcomes in COPD, yet its role in airway remodeling remains unclear. To this end, an elastase-induced COPD model was established, followed by colonization with Pneumocystis. Lung tissue was analyzed histologically and molecularly to assess epithelial thickness, alveolar morphometric parameters (mean linear intercept [MLI], D₀, D₁, D₂), inflammation, collagen deposition, and the expression of remodeling and oxidative stress markers. Emphysematous damage parameters MLI, D₀, D₁, and D₂ were markedly elevated in co-exposed animals, indicating enhanced alveolar enlargement. Animals with COPD and Pneumocystis colonization showed a significant increase in airway inflammation compared with control, COPD, and Pneumocystis groups. Airway epithelial thickness, mucus metaplasia, and collagen deposition exhibited a summative increase in the COPD/Pneumocystis group. Redox-responsive markers, such as superoxide dismutase (SOD) and catalase, were upregulated. Moreover, protein and mRNA levels of nuclear factor erythroid 2–related factor 2 (Nrf2) and its downstream gene heme oxygenase-1 (Hmox1) were significantly increased, with the strongest activation observed in co-exposed animals. Integrative correlation analysis showed that Pneumocystis burden positively correlated with lung damage, inflammation, and epithelial remodeling. These structural alterations were accompanied by coordinated activation of the antioxidant pathway Nrf2. Taken together, Pneumocystis colonization is associated with enhanced pulmonary remodeling and modulation of antioxidant signaling in experimental COPD, promoting structural and molecular changes that may contribute to disease progression. These findings suggest that Pneumocystis acts as an amplifying factor in COPD-associated lung damage. Full article

This study investigates the antioxidant properties of several synthetic peptides derived from milk proteins previously identified in milk permeate, a by-product of the dairy industry. The aim of the research is to identify which peptides present in milk permeate are responsible for its antioxidant activity. A comprehensive experimental strategy was employed to evaluate their antioxidant potential, including in silico selection, in vitro free radical scavenging assays and cellular models using Caco-2 and HCT116 cell lines. The peptides were screened using a molecular docking approach for their potential interaction with the Kelch-like ECH-associated protein 1/nuclear factor erythroid 2-related factor 2 (Keap1/Nrf2) pathway, and eight out of twenty-eight were selected and synthesized for further analyses. In vitro, six of the selected peptides demonstrated significant direct antioxidant activity in the DPPH scavenging assay, and two in the ABTS scavenging test. In cellular environments, three peptides (LPAPELGPRQA, LPIIQKLEPQI and NGQVWEESLKRL) effectively protect cells from oxidative stress induced by tert-butyl hydroperoxide, reducing reactive oxygen species production and partially mitigating lipid peroxidation. Further investigation showed that two of them (LPAPELGPRQA and LPIIQKLEPQI) effectively induce the Keap1/Nrf2 pathway, as evidenced by a ∼1.5-fold increase in Nrf2 levels and overexpression of downstream proteins. Permeability studies revealed that these peptides can cross the intestinal monolayer (2–3% in 2 h), suggesting potential systemic effects. Overall, these findings highlight the multifunctional antioxidant properties of the investigated peptides and support their potential application as nutraceuticals or therapeutic agents for oxidative stress-related conditions. Full article

In 1988, two seminal studies were published almost simultaneously in the same scientific journal. Both spurred the field of brain energy metabolism research in new directions, culminating in a long-lasting debate that appeared to split its practitioners into two factions that seem unwilling to agree on what metabolic processes are fueling the active brain with adenosine triphosphate (ATP). The first study used rat hippocampal slices to demonstrate the ability of lactate to support neuronal function as the sole oxidative mitochondrial substrate. The second study demonstrated that upon brain stimulation, glucose consumption is not accompanied by respective oxygen consumption, but a non-oxidative glucose utilization or what has become known as “aerobic glycolysis”. Consequently, for almost four decades, researchers in this field have been divided between those who profess that brain activity is supported by oxidative lactate metabolism and those who insist that non-oxidative glucose metabolism supports it. Hypotheses for both concepts were offered, “The Astrocyte Neuron Lactate Shuttle Hypothesis” and “The Efficiency Tradeoff Hypothesis,” respectively. To bridge the gap between the two groups, a recent editorial, authored by over twenty leading investigators, was published. The editorial received two separate responses from investigators who supported the non-oxidative glucose consumption as the main process supporting neural activity, signaling that the gap between the two groups remained. The present perspective highlights the principal disagreements that divide this utmost important field of research. It argues that the main reason for these disagreements is rooted in the assumption that pyruvate is the end-product of aerobic glycolysis, even when many among those who adhere to this assumption accept that in the active brain glycolysis is the main provider of the necessary ATP and the end-product is lactate under aerobic conditions. The consideration of a paradigm shift, according to which lactate is the real end-product of glycolysis, independent of the presence or absence of oxygen, could bridge the great divide between those who separate glycolysis into two outcomes and those who profess that there is only one, prefix-less glycolytic pathway that always ends with the production of lactate. Full article

Neurovascular coupling (NVC) maintains appropriate cerebral blood flow (CBF) in response to neuronal activity, and its disturbance, known as neurovascular uncoupling (NVU), is increasingly recognised as a major contributor to neurodegenerative disease. Alzheimer’s disease (AD) NVU is caused by Aβ buildup, tau pathology, endothelial dysfunction, and persistent neuroinflammation, leading to poor CBF control and blood–brain barrier (BBB) disintegration. Parkinson’s disease (PD) is characterised by α-synuclein aggregation, oxidative stress, mitochondrial dysfunction, and dopaminergic neuronal loss, all of which impede cerebrovascular regulation. These disease-specific mechanisms interact via similar vascular pathways, establishing NVU as a critical connection between neuronal degeneration and cerebrovascular dysfunction. This study highlights the critical role of NVU in neurodegeneration by investigating shared and disease-specific processes in AD and PD. Tau pathology disturbs vascular regulation in AD, whereas dopaminergic neuron loss impairs cerebrovascular control in PD. Both Aβ and α-synuclein are linked to endothelial dysfunction and oxidative stress, albeit originating in different pathologies. Comparative analysis reveals distinct vascular abnormalities in each condition, as well as shared processes such as inflammation and BBB disruption. The study also covers developments in biomarker discovery and neuroimaging techniques that allow for exact characterisation of NVU, facilitating early diagnosis and treatments. In addition, lifestyle changes and pharmacological treatments for oxidative stress and endothelial injury are being examined. This study highlights the significance of NVU as a fundamental pathogenic mechanism, underscoring its importance for comprehending disease development and formulating novel therapeutic strategies. Full article

The neuropeptides vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) have emerged as potent modulators of immune responses during sepsis, yet their roles remain complex, alternating between protective and permissive depending on timing, tissue compartment, and inflammatory context. This review presents a historical assessment of VIP and PACAP in sepsis research, highlighting the evolution of conceptual advances across five decades. Starting in the 1980s, early studies revealed that VIP levels rise during endotoxemia and correlated with hypotension and mortality, suggesting a deleterious role. By the 1990s, research pivoted toward understanding gut-derived VIP and its interaction with nitric oxide, culminating in the classification of VIP and PACAP as “macrophage deactivating factors” that downregulate TNFα and IL-6. The 2000s further clarified their cell-specific actions through VPAC1/2 and PAC1 receptors, showing anti-inflammatory effects on both innate and adaptive immune cells, while illuminating delivery challenges overcome by liposomal encapsulation. The 2010s expanded this narrative by dissecting receptor dynamics, gut barrier regulation, and VIP’s role in neuroimmune crosstalk and thrombo-inflammation. Most recently, studies in the 2020s provide a nuanced view of how VIP suppresses inflammatory damage but also enables pathogen persistence during live bacterial infection, implicating VIP signaling in trade-offs between tolerance and clearance. Across this chronological framework, VIP and PACAP have oscillated between friend, foe, and frenemy, underscoring the importance of context in leveraging their therapeutic potential in sepsis. Full article

Air pollution represents a critical yet modifiable factor influencing the recurrence and progression of upper-airway infections. This review explores the molecular, immunological, and environmental mechanisms linking airborne pollutants to recurrent sinus and respiratory tract inflammation. Particular focus is placed on pollutant-induced oxidative stress, epithelial barrier disruption, alterations in the microbiome, and immune dysregulation, which collectively heighten disease susceptibility. Integrating recent advances in exposomics, multi-omics, and artificial intelligence, the discussion highlights new approaches to unravel exposure–response pathways and identify predictive biomarkers. Future directions emphasize precision exposure assessment, interventional strategies to improve air quality, and the emerging framework of “clean-air medicine” to guide prevention and policy. Overall, this synthesis underscores the urgent need for multidisciplinary collaboration across environmental science, molecular biology, and clinical research to mitigate the growing burden of pollution-related airway disease and promote sustainable respiratory health. Full article

Cutaneous melanoma is the most lethal form of skin cancer because of its aggressiveness, rapid metastasis, and high therapeutic resistance. The 2018 World Health Organization (WHO) classification emphasized that melanoma comprises distinct subtypes defined by cumulative sun damage, site of origin, and molecular characteristics, which explain differences in mutational burden, immunogenicity, and treatment response. Immunotherapy with anti-PD-1 therapy such as nivolumab and pembrolizumab changed the therapeutic landscape by restoring CD8+ T-cell activity and improving survival. Still, many patients show primary or acquired resistance influenced by low PD-L1 expression, loss of antigen presentation, tumor metabolic plasticity, and an immunosuppressive microenvironment. Mitochondria are central to this process. They regulate ATP generation through oxidative phosphorylation (OXPHOS), redox control, apoptosis, and the metabolic programming needed for T-cell activation. In the tumor microenvironment (TME), hypoxia, nutrient restriction, and PD-1 signaling reduce mitochondrial biogenesis, increase fission and reactive oxygen species (ROS) accumulation, and lead to exhaustion and impaired effector function. Moreover, tumor cells outcompete immune cells for key nutrients such as glucose and glutamine, while increased lactate production and extracellular acidosis further suppress mitochondrial respiration in T cells. Strategies to overcome resistance include restoring oxidative metabolism, activating PGC-1α, supplying metabolic substrates, and combining checkpoint blockade with inhibitors of glycolysis or glutaminolysis to enhance the immune response. Full article

Gold nanoparticles (AuNPs) have numerous applications in science and industry. Therefore, their potential phytotoxicity should be investigated. Garden cress (Lepidium sativum L.) is a useful model plant for assessing the effects of chemicals released into the environment. The aim of this study was to prepare alginate gels containing AuNPs for plant exposure experiments, evaluate their physicochemical properties, and determine their effects on selected biochemical parameters of garden cress seedlings. Gold nanoparticles were synthesized in sodium alginate at an initial concentration of 50 mg/L, using xylose and maltose as reducing agents. The gels were diluted with distilled water to obtain AuNP concentrations of 5 and 25 mg/L. Garden cress seeds were placed on filter paper soaked with the tested formulations, while distilled water and sodium alginate solutions without AuNPs served as controls. After 5 days of incubation at 20 °C under light conditions, the plant material was collected and selected bioactive compounds were determined. AuNP-containing gels significantly affected the biochemical status of the seedlings. In particular, AuNPs synthesized with xylose at 25 mg/L significantly increased the contents of photosynthetic pigments and total polyphenolic compounds. All tested AuNP formulations increased the antioxidant activity of seedlings, suggesting the activation of abiotic stress-related defense responses, however, direct markers of oxidative damage were not assessed in the present study. Overall, the results indicate that alginate-based AuNPs can modify selected biochemical parameters in garden cress seedlings, and these effects depend on nanoparticle concentration and reducing sugar used during synthesis, which may be relevant for the future development of plant-targeted nanomaterials for agricultural applications. Full article

Gastric cancer remains a highly heterogeneous malignancy in which chemotherapy response is limited by intrinsic and acquired resistance, cumulative toxicity, and the restricted predictive value of conventional preclinical models. This review critically synthesizes evidence on selected medicinal plants and their bioactive phytocompounds as adjuncts to standard chemotherapy for gastric cancer, with an emphasis on mechanistic plausibility, preclinical synergy, and translational barriers. Across the reviewed literature, phytocompounds from Curcuma longa, Scutellaria baicalensis, Camellia sinensis, Syzygium aromaticum, Glycyrrhiza glabra, Allium sativum, Marsdenia tenacissima, and Rhus verniciflua showed anticancer or chemopreventive activity through multitarget effects on apoptosis, proliferation, invasion, inflammation, oxidative stress, and resistance-associated signaling. The most convincing chemosensitizing evidence involved curcumin, wogonin, baicalein, EGCG, which enhanced the activity of fluoropyrimidines, platinum agents, paclitaxel, doxorubicin, or related antitumor regimens in selected gastric cancer models. However, the evidence base remains heterogeneous and is constrained by variable extract standardization, incomplete dose reporting, poor bioavailability, insufficient pharmacokinetic/pharmacodynamic integration, and underuse of clinically relevant model systems. Overall, medicinal plant bioactives remain promising adjunct candidates in gastric cancer. Still, meaningful translation will require chemically defined interventions, rigorous synergy analysis, interaction-aware study design, and validation in advanced preclinical and clinical settings. 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