Search Results (4,107)

This study evaluates volatile extracts (HE1 and HE2) from the lichen Pseudevernia furfuracea as eco-friendly agents to control algal proliferation, specifically targeting the cyanobacterium Microcystis aeruginosa and the green microalga Chlorella sorokiniana. Both extracts exhibited potent anti-microalgal activity against the two species with a minimum inhibitory concentration (MIC) ranging from 375 to 750 µg/mL. Furthermore, both extracts reduced cell density by more than 98% after eight days of treatment. Chlorophyll a and protein levels decreased significantly (>80%) in both species, indicating suppression of pigment synthesis. However, their physiological responses were distinct: M. aeruginosa underwent early acute oxidative stress and severe membrane damage, while C. sorokiniana exhibited delayed oxidative activation and a negative growth rate, suggesting non-lytic metabolic inhibition. An in silico study by molecular docking of the most abundant compounds identified in these volatile extracts, such as terpenoids (abietatriene, δ-cadinene) and a phenolic compound (atraric acid), showed that these compounds interact with vital cellular targets in M. aeruginosa and C. sorokiniana and likely contribute to the effects observed in these two species. Predictive toxicity by applying the ADMET framework confirmed the favorable bioavailability and low acute toxicity of these volatile compounds. Therefore, P. furfuracea volatiles are promising, species-specific, and environmentally safe candidates for mitigating aquatic algal proliferation through targeted oxidative and metabolic interference. Full article

Gatifloxacin (GTFX), a fourth-generation fluoroquinolone, causes metabolic disturbances in mammals, but its hepatotoxic mechanisms in aquatic vertebrates remain unclear. This study investigated whether GTFX induces liver injury in zebrafish larvae through oxidative stress or alternative pathways. Larvae at 3 days post-fertilization were exposed to 0.2–2.3 mg/mL GTFX for 48 h. Liver morphology, histopathology, intracellular reactive oxygen species (ROS), and expression of lipid metabolism (pparg) and xenobiotic biotransformation genes (cyp1a, cyp1b1) were assessed. GTFX exposure caused concentration-dependent reductions in liver area, increased hepatic opacity, delayed yolk sac absorption, and hepatocyte swelling with cytoplasmic vacuolization. Despite these structural changes, ROS levels did not differ significantly from those of controls. In contrast, transcriptional analysis revealed significant upregulation of pparg, cyp1a, and cyp1b1, indicating disrupted lipid homeostasis and enhanced detoxification responses. Acute high-dose GTFX exposure induced a metabolism-associated hepatotoxic response in zebrafish larvae, which occurred without a statistically significant change in bulk ROS levels. Together, these findings offer mechanistic insight into fluoroquinolone-associated liver injury. Full article

Background/Objectives: Sepsis is a life-threatening syndrome arising from a dysregulated host response to infection, frequently leading to multiple organ dysfunction, with the lungs being among the most severely affected organs. Oxidative stress, inflammation, apoptosis, and DNA damage play key roles in the pathogenesis of sepsis-induced acute lung injury (ALI). Beyond its lipid-lowering effects, rosuvastatin possesses anti-inflammatory and antioxidant properties that may confer protective effects in sepsis. This study was designed to investigate the dose-dependent prophylactic efficacy of rosuvastatin in mitigating pulmonary damage in rats with cecal ligation and puncture (CLP)-induced sepsis. Methods: Sprague–Dawley rats were randomly divided into six groups: Sham, Sham + rosuvastatin (10 mg/kg), Sham + rosuvastatin (20 mg/kg), CLP, CLP + rosuvastatin (10 mg/kg), and CLP + rosuvastatin (20 mg/kg). Rosuvastatin was administered via oral gavage 4 h before the surgical procedures in the experimental groups. All animals were sacrificed 16 h following surgical procedures. Lung tissues were analyzed for biochemical markers, including malondialdehyde (MDA) and reduced glutathione (GSH), as well as histopathological changes and immunohistochemical expression of NF-κB/p65, caspase-3, and 8-OHdG. Results: CLP-induced sepsis significantly increased MDA levels while decreasing GSH levels, indicating enhanced oxidative stress. Rosuvastatin treatment significantly reversed these changes. Histopathological analysis revealed marked lung injury in the CLP group, including alveolar inflammation, interstitial inflammation, vascular congestion, and increased alveolar septal thickness, all of which were significantly reduced following rosuvastatin administration. Immunohistochemical findings demonstrated increased expression of NF-κB/p65, caspase-3, and 8-OHdG in the CLP group, whereas rosuvastatin significantly attenuated these expressions. No significant difference in prophylactic efficacy was observed between the 10 mg/kg and 20 mg/kg doses of rosuvastatin. Conclusions: Rosuvastatin demonstrated a protective effect against sepsis-induced pulmonary damage by reducing oxidative stress, inflammation, apoptosis, and DNA damage. These findings suggest that rosuvastatin may have prophylactic potential in sepsis; however, further support is needed from investigations of cellular pathways in different mechanistic directions. Full article

Background/Objectives: Long COVID-19 (LC-19), also known as Post-Acute COVID-19 Syndrome (PACS), is a chronic condition some people experience after an initial SARS-CoV-2 infection. The etiology of this complex, multifactorial disease remains largely unknown, although various theories have been propounded. This study aims to profile and compare the metabolic activity of cells of normal and LC-19 patients. Methods: A cohort of 20 individuals, 10 with LC-19 and 10 without LC-19, was selected based on their post-COVID-19 symptomatology. Saliva was tested for opportunistic viruses like Epstein–Barr virus (EBV) and Human Herpesvirus 6 (HHV-6). Lymphoblastoid cell lines derived from blood were analyzed using the Biolog Phenotype Mammalian Microarrays (PM-M1, PM-M6, and PM-M7) to assess metabolic activity across a wide array of growth substrates and effector molecules. Results: Unique metabolic profiles emerged across the controls and LC-19 groups. The SARS-CoV-2 infection causes an over two-fold enhanced utilization of glycolytic and anaerobic substrates and a reduced response to growth factors and effectors. The increased energy source utilization assessed in PM-M1 is unsustainable, and the LC-19 groups demonstrate this with a clear correlation with the number of LC-19 symptoms, demonstrating a trend consistent with metabolic reprogramming. The infection also results in a reduced response to growth factors and effectors, assessed in PM-M6 and PM-M7, with the level of reduction commensurate with the symptom burden. Conclusions: The data from the patient groups were analyzed and compared to construct a metabolic profile unique to individuals who developed LC-19, which could, in the future, be used for diagnosis and to identify targets for therapeutic intervention. Our study identified an LC-19-specific metabolic profile indicative of adaptive responses to stress, cellular dysfunction, and prolonged inflammation, leading to the reprogramming of bioenergetic pathways. Full article

Road traffic crashes remain a global public health burden and a persistent resource allocation problem that undermines progress toward the sustainable development of safe, equitable mobility systems. Saudi Arabia’s Vision 2030 targets fewer than 10 fatalities per 100,000 population, a goal aligned with United Nations Sustainable Development Goal 3.6 (halving road traffic deaths) and SDG 11.2 (safe and sustainable transport), yet a gap persists between crash prediction research and how agencies deploy enforcement resources. This paper builds a closed-loop predict–optimize–evaluate framework connecting Long Short-Term Memory (LSTM) neural networks to a goal-distance gap metric and constrained optimization, feeding forecast outputs directly into enforcement scheduling decisions. Using monthly casualty data from official Saudi sources covering the entire kingdom (all 13 administrative regions) from 2010 through 2024 (N = 42,856 fatal and serious injuries across 180 monthly observations), we validate LSTM forecasting against five benchmarks plus a GRU and a Transformer baseline, apply gap analysis as a standardized goal-distance metric, optimize enforcement allocation with triangulated elasticity estimates, and evaluate past policy reforms through multi-method counterfactual analysis. A headline finding is that roughly 28% of fatal and serious injuries cluster within only about 6% of weekly hours, creating an unusually concentrated target for enforcement reallocation. The LSTM achieves RMSE = 2.47 with MASE = 0.83, beating ARIMA by 35% while maintaining robustness during COVID disruptions (RMSE = 2.38 in the post-acute period 2022–2024 versus 2.61 in the acute period 2020–2021). Temporal analysis confirms 28% of fatalities (95% CI: 26.0–30.0%) cluster within 6% of weekly hours. Enforcement elasticity triangulated from three independent sources converges at α ≈ 0.31 (90% CI: 0.25–0.40). The optimization model allocates 56% of enforcement resources to Thursday–Friday midnight-to-4 AM windows, projecting a 17.1% casualty reduction (90% CI: 13.5–20.6% under Monte Carlo uncertainty in α). Monte Carlo sensitivity analysis with 10,000 iterations confirms a median benefit-cost ratio of 1.88 (90% CI: 1.18–2.97), with P (BCR > 1.0) = 98.9%, using locally calibrated VSL = SAR 4.2 million (equivalent to approximately USD 1.12 million at the SAMA-pegged rate of 3.75 SAR/USD, in constant 2024 prices). Counterfactual evaluation finds that the post-2018-reform period was associated with a 22.1% casualty reduction (95% CI: 16.4–27.8%), with magnitude robust across four methods (LSTM counterfactual, Bayesian Structural Time-Series, Synthetic Control, and an inverse-variance-weighted synthesis of the three); we stress, however, that attribution to the driving reform itself cannot be cleanly separated from concurrent Saher camera expansion, public awareness campaigns, and trauma-care improvements. By translating prediction into evidence-based, resource-efficient enforcement, the framework supports sustainable road safety policy in middle-income and rapidly motorizing settings. Full article

Background: T-cell acute lymphoblastic leukemia (T-ALL) remains a challenging malignancy with limited targeted therapies. Natural phenanthrene derivatives represent a promising source of antileukemic agents. Objective: We screened a library of natural phenanthrene-type compounds to identify cytotoxic leads in Jurkat T-ALL cells and investigated the mechanisms underlying their activity, including potential synergy with the proteasome inhibitor bortezomib (BTZ). Methods: Jurkat cells were treated with thirteen natural compounds at 10 and 20 µM for 48 h; cell viability was assessed by WST-1 cell viability assay. Dose–response curves were generated to calculate IC₅₀ values. Apoptosis was evaluated by Hoechst 33342/PI staining and Annexin V/PI flow cytometry. Synergy with BTZ was analyzed using a fixed-ratio combination index (CI) approach and IC₅₀ shift analysis. ER stress signaling was characterized by Western blotting, quantitative RT-PCR of UPR genes (GRP78, ATF6), and immunoprecipitation of GRP78 followed by ubiquitin immunoblotting. Results: Among the compounds screened, Cypripedin showed the most potent cytotoxicity with an IC₅₀ of 6.52 µM. It induced a dose-dependent increase in apoptosis. Combination with BTZ yielded a CI < 0.5 and reduced BTZ IC₅₀ from 3.43 to 1.88 ng/mL. Cypripedin activated the unfolded protein response (UPR), modulated key ER stress markers including GRP78, p-PERK, p-eIF2α, p-JNK, and ATF6, downregulated UPR gene transcripts, and promoted GRP78 ubiquitination. Molecular docking predicted strong binding of Cypripedin to the GRP78 ATPase domain (Vina score −7.630 kcal/mol), supporting its mechanism of action. Conclusion: Cypripedin induces apoptosis in Jurkat T-ALL cells, synergizes with BTZ, and modulates ER stress through GRP78 ubiquitination. These findings support its further development as a potential T-ALL therapeutic. Full article

Ischemic stroke is an acute cerebrovascular disease with high disability and morbidity. However, therapeutic approaches are restricted by a narrow time window for reperfusion. Astilbin has various pharmacological activities and good therapeutic potential against ischemic stroke and neurodegenerative diseases. Nevertheless, Astilbin’s mechanism of action remains unclear. Here, we used an integrated strategy that includes network pharmacology, omics validation, and functional verification. Potential targets of Astilbin were predicted using SwissTargetPrediction and PharmMapper, and cross-analyzed with IS-related genes from multiple databases. GO/KEGG enrichment analyses showed that Astilbin synergistically regulates stroke-associated pathways (e.g., MAPK, AGE-RAGE). Combined transcriptomic and metabolomic assays confirmed that Astilbin ameliorates OGD/R-induced oxidative stress and metabolic disorders by modulating the MAPK and ferroptosis pathways. Molecular docking and dynamics simulations revealed that Astilbin has high affinity for core targets (ERK1/2, CREB, p90RSK, MMP9) and binds stably to MMP9. Using an OGD/R-injured neuronal-like PC12 cell line, in vitro assays confirmed that Astilbin alleviates oxidative stress, calcium overload, lipid peroxidation, and intracellular iron levels, while also modulating apoptosis- and inflammation-related genes. Overall, this study has established a comprehensive pharmacological framework for the use of Astilbin against IS, clarified its multi-target, multi-pathway neuroprotective mechanisms of action, and provided evidence for its potential in the treatment of IS. Full article

Serum S100B has been proposed as a peripheral biomarker associated with neuroinflammatory and astroglial stress-related processes in major depressive disorder (MDD). This study aimed to evaluate serum S100B levels in patients with MDD and suicidal ideation and to investigate whether childhood trauma mediates the relationship between suicide probability and S100B levels. This study included patients with MDD and suicidal ideation (n = 29), patients with MDD without suicidal ideation (n = 30), and healthy controls (n = 29). Serum S100B levels were measured before and after treatment in patients with suicidal ideation. Suicide Probability Scale (SPS), Childhood Trauma Questionnaire (CTQ), and Rosenberg Self-Esteem Scale (RSES) scores were assessed. Group comparisons were performed using Mann–Whitney U and Kruskal–Wallis tests with Dunn–Bonferroni post hoc analysis. Logistic regression and mediation analyses were conducted to examine the relationships among suicide probability, childhood trauma, and S100B levels. Pre-treatment serum S100B levels were significantly higher in patients with MDD and suicidal ideation compared with healthy controls (median 10.95 vs. 8.97 pg/mL, p = 0.001), whereas post-treatment levels did not differ between groups (median 7.84 vs. 8.97 pg/mL, p = 0.323). Within-group analysis demonstrated a significant reduction in S100B levels after treatment (Z = −3.359, p < 0.001). Additional three-group comparison revealed a significant overall difference in S100B levels among the study groups (H = 8.17, p = 0.017). Logistic regression analysis showed that serum S100B levels were independently associated with suicidal ideation (OR = 1.14, 95% CI 1.02–1.27, p = 0.021). Mediation analyses demonstrated a significant indirect effect of suicide probability on S100B levels through childhood trauma (Sobel Z = −2.45, p = 0.014). Serum S100B levels were elevated during the acute phase of MDD with suicidal ideation and decreased following treatment; however, the specificity of this longitudinal change to suicidality could not be determined within the present study design. The relationship between suicide probability and S100B levels appears to be mediated by childhood trauma, suggesting that S100B may reflect trauma-related neurobiological vulnerability rather than a disease-specific biomarker of suicidality. These findings support a potential association between peripheral glial-related biomarkers and stress-responsive neurobiological processes underlying suicidality. Full article

Acute respiratory distress syndrome (ARDS) is characterized by systemic inflammation, immune dysregulation, oxidative stress, and frequent extrapulmonary organ involvement. Neurological complications of ARDS, such as neuroinflammation, cognitive impairment and delirium, are common and worsen outcomes. Early evidence highlights bidirectional communication between the lungs and brain, the lung–brain axis, through which inflammation may amplify both pulmonary and cerebral injury. This narrative review synthesizes recent experimental and clinical data on the immunomodulatory and neuroprotective effects of commonly used sedative agents in ARDS, focusing on their influence on inflammatory mediators (IL-1β, IL-6, IL-8, IL-10, TNF-α) and neuronal injury biomarkers (S100B, neuron-specific enolase). Sedative agents seem to exert effects beyond sedation by modulating systemic and neuroinflammatory responses. Evidence suggests they can influence cytokine profiles and reduce biomarkers associated with neuronal injury, potentially mitigating neuroinflammation and delirium in ARDS patients. Sedatives may modulate lung–brain crosstalk in ARDS through immunoinflammatory pathways, integrating sedative and neuroprotective effects. Mechanistic clarification may enable targeted sedation strategies to improve pulmonary and neurological outcomes. Full article

Background: Chronic critical illness (CCI) following acute brain injury involves persistent immune dysfunction, yet its genetic determinants remain unclear. We investigated whether the rate of T-cell receptor excision circle (TREC) depletion—a proposed marker of adaptive homeostatic resilience—is associated with the burden of rare damaging genetic variants. Methods: Whole-exome sequencing (WES) was performed on a cohort of 84 patients (64 with traumatic brain injury, 20 with stroke). In a longitudinal sub-cohort (n = 27), patients were stratified into quartiles (Q1–Q4) based on the slope of their TREC trajectories. ‘Qualifying variants’ (QVs) were defined using strict rarity (gnomAD allele frequency ≤ 0.001) and pathogenicity criteria. Gene-level burden (collapsing) analysis and permutation-based statistical testing (10,000 iterations) were employed to evaluate genetic enrichment in the extreme quartiles. Results: While baseline TREC levels were strictly age dependent (p < 0.0001), the rate of change (TREC slope) was age independent. Rapid TREC decline (Q1) correlated with significantly higher final SOFA scores (p = 0.001) and neutrophil-to-lymphocyte ratios (p = 0.020). Rare variant burden analysis revealed that Q1 patients were significantly more likely to harbor QVs in immune-related genes compared to the Q4 recovery group (odds ratio = 8.25; permutation p = 0.016). Patients with rapid decline were enriched for QVs in putative core “housekeeping” pathways essential for T-cell maintenance and DNA repair (e.g., ERCC3, FANCM), whereas variants in recovering patients were restricted to peripheral effector or structural pathways. Conclusions: Our findings suggest, as a conceptual framework, that an individual’s ability to maintain T-cell homeostasis during critical illness is influenced by their underlying genetic buffering capacity. We propose a hypothetical “two-hit” framework where physiological stress unmasks pre-existing fragilities in core homeostatic pathways—potentially reflecting a state of functional haploinsufficiency under extreme proliferative demand—leading to accelerated immune exhaustion. These results position the TREC slope as a dynamic, age-independent biomarker of genomic resilience in the ICU. All findings are exploratory and hypothesis generating. Full article

Heat stress is a major constraint to productivity and physiological homeostasis in laying hens. This study investigated integrated responses to acute heat stress using a multi-omics approach, including performance traits, serum biochemical parameters, histology, hepatic transcriptomics, cecal metagenomics, and metabolomics. Acute heat stress impaired productive performance, as reflected by changes in egg production and reduced eggshell strength, and induced systemic physiological disturbances, including increased stress- and injury-related blood indicators and disrupted metabolic and electrolyte balance. Histological analysis confirmed liver and intestinal tissue damage. Hepatic transcriptomics revealed inflammatory activation and suppression of metabolic pathways, particularly those involved in lipid metabolism, energy production, and redox homeostasis. Cecal metagenomic and metabolomic analyses showed altered microbial composition and functional potential, along with disruptions in amino acid, lipid, and energy metabolism. Collectively, these findings suggest that acute heat stress is associated with coordinated inflammatory responses and metabolic reprogramming, together with liver and intestinal injury and gut microbiota–metabolite alterations. The study provides a framework for understanding early heat stress responses and highlights potential targets for nutritional and microbiota-based interventions in poultry production. Importantly, serum biochemical indicators such as D-lactic acid and aspartate aminotransferase may serve as potential early biomarkers for monitoring heat-stress-induced physiological disturbances. Full article

Endotoxemia represents a life-threatening clinical disorder driven by an aberrant host immune response to pathogenic infection, often resulting in severe multiple organ dysfunction. Among its most devastating complications are acute lung injury (ALI) and endotoxemia-associated encephalopathy (EAE), both of which are associated with elevated mortality and currently lack effective targeted interventions. This study evaluated the therapeutic efficacy and underlying molecular mechanisms of recombinant human thymosin β4 (rhTβ4) in a murine model of lipopolysaccharide (LPS)-induced endotoxemia. Our results showed that treatment with rhTβ4 markedly enhanced survival rates and diminished the systemic overproduction of diverse proinflammatory cytokines and chemokines in endotoxemic mice. These systemic protective actions were achieved through the inhibition of the TLR4/NF-κB signaling cascade, the reduction in M1 macrophage polarization, and the simultaneous alleviation of mitochondrial impairment and oxidative stress. Moreover, rhTβ4 treatment significantly rescued EAE-related cognitive deficits and attenuated neuronal damage, primarily through the suppression of neuroinflammation and microglial overactivation. Integrative transcriptomic profiling and functional assays identified lysophosphatidic acid receptor 3 (LPAR3) as an important contributor, suggesting that rhTβ4 suppresses microglial-mediated neurotoxicity at least in part through LPAR3 downregulation. In conclusion, rhTβ4 confers robust multi-organ protection against endotoxemic injury by orchestrating the inhibition of systemic and central neuroinflammatory cascades, positioning it as a promising candidate for the treatment of endotoxemia-induced ALI and EAE. Full article

Aristotelia chilensis (maqui berry) is a Chilean native fruit rich in anthocyanins with potential antioxidant, glycemic, cardiometabolic, and ocular benefits, but its clinical efficacy remains unclear. This systematic review synthesized and critically appraised human trials evaluating oral maqui supplementation in adults. Following PRISMA 2020 and a PROSPERO-registered protocol, five databases were searched, and risk of bias and certainty of evidence were assessed using RoB 2/ROBINS-I and GRADE. Twelve clinical trials published between 2014 and 2023 were included. Acute studies consistently showed reduced postprandial glucose and modulation of insulin response, whereas chronic interventions showed modest and inconsistent effects on HbA1c, lipid profile, and other cardiometabolic markers. Favorable changes were also reported for oxidative stress biomarkers and autonomic parameters, although these findings were mainly based on surrogate endpoints. The most consistent evidence was observed in the ocular domain, where maqui supplementation improved tear production, dry eye symptoms, and tear inflammatory markers. The overall certainty of evidence ranged from moderate to very low because of methodological heterogeneity, small sample sizes, and short intervention duration. Maqui berry supplementation shows promise, particularly for acute glycemic control and ocular surface health, but larger long-term randomized trials using standardized formulations are needed before definitive clinical recommendations can be made. Full article

Caloric restriction (CR) is known to activate a broad spectrum of cytoprotective signaling pathways and enhance tissue tolerance to various stressors, including those associated with the cytotoxic effects of pharmaceutical agents. Nephrotoxic drugs, such as aminoglycoside antibiotics, remain a major clinical concern due to their frequent use and potential to cause acute kidney injury (AKI), for which effective preventive strategies are still limited. In this study, we investigated whether CR applied for 5 weeks (4-week pretreatment + 1-week concurrent with AKI induction) can alleviate AKI triggered by the antibiotic gentamicin, with a focus on evaluating changes in antioxidant-related parameters and autophagy-associated signaling during CR-mediated nephroprotection. CR’s nephroprotective effects were evaluated using diagnostic assays, Western blotting, and histological analysis. Additionally, oxidative stress markers and mitochondrial integrity were assessed to analyze the impact of CR on antioxidant-related pathways. CR significantly improved renal function and structure, with reduced kidney injury markers (KIM-1, NGAL) and alleviated histological damage. Critically, CR mitigated oxidative stress, evidenced by decreased thiobarbituric acid reactive substances (TBARS) and protein carbonylation, as well as increased levels of the reduced form of glutathione and activity of glutathione peroxidase (GPx). A lowered Bcl-X_L/X_S ratio was consistent with reduced apoptotic signaling, while reduced leukocyte infiltration reflected attenuated renal inflammation. Additionally, a reduction in mitochondrial DNA (mtDNA) lesions suggested that CR was associated with modulation of mitochondrial and metabolism-related pathways, with concurrent improvements in mitochondrial stability. Our findings demonstrate that CR attenuated gentamicin-induced AKI and was associated with changes in antioxidant-related parameters, reduced mtDNA damage, a decrease in inflammatory cell infiltration, and modulation of autophagy-related signaling. Full article

The pancreas is an organ with two functions: endocrine and exocrine. The proper functioning of the pancreas depends on many factors. One of these is trace elements—precise control of trace element homeostasis is important for both the endocrine and exocrine parts. This review provides a comprehensive summary of current knowledge regarding the role of trace elements: iron (Fe), copper (Cu), cobalt (Co), iodine (I), manganese (Mn), zinc (Zn), silver (Ag), cadmium (Cd), mercury (Hg), lead (Pb), and selenium (Se) in pancreatic physiology and their influence on the pathogenesis of key diseases of this organ, such as diabetes (DM), acute (AP) and chronic pancreatitis (CP), autoimmune pancreatitis (AIP), and pancreatic cancer (PC). Trace elements, including Fe, Cu, Zn, Se, and Mn, play a fundamental role in maintaining endocrine and exocrine homeostasis, participating in insulin synthesis, stabilizing digestive enzymes, and the functioning of antioxidant systems. It has been demonstrated that disturbances in their concentrations lead to the activation of pathological molecular pathways, including oxidative stress, chronic inflammation, and beta-cell apoptosis. In the context of diabetes, excess Fe promotes ferroptosis, whilst exposure to heavy metals such as Cd, Pb, and Hg induces insulin resistance and pancreatic islet dysfunction. In the course of pancreatitis, elements such as Zn and Se exhibit protective potential by stabilizing tissue barriers, whereas toxic metals impair ion transport, exacerbating fibrotic processes. Furthermore, analysis of available data indicates a significant association between heavy metal accumulation and pancreatic carcinogenesis, driven by DNA damage and oncogene modulation. Understanding pancreatic metallomics opens new prospects for early diagnosis, environmental prevention, and the development of targeted therapeutic strategies that restore the body’s micronutrient balance. Full article