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Heavy metal pollution has become a critical concern in agricultural ecosystems driven by a complex matrix of industrial practices, high-input fertilizers, metal-based agrochemicals, and wastewater irrigation. While the previous literature typically highlights general physiological symptoms of heavy metal stress, this review provides a novel, comprehensive framework that bridges three independent pillars: specific industrial applications dictating elemental pathway, localizes active root-zone transport kinetics, and an engineering-based evaluation of emerging remediation strategies. We systematically synthesized literature from 2000 to 2026 across major databases (WoS, PubMed and Google Scholar), applying strict inclusion criteria based on data validation, experimental reproducibility, and mechanistic depth. We examine the geochemical behavior, cellular toxicity, and plant resilience mechanics of seven priority elements like cadmium, lead, arsenic, aluminum, mercury, chromium and molybdenum. Rather than merely reiterating superficial visual damage like chlorosis or stunted growth, we focus on physiological and molecular root causes of phytotoxicity, including the structural hijacking of essential nutrient networks, intracellular reduction cascades and organelle-specific oxidative disruption. This review also discussed the discovery of specialized, energy-dependent eukaryotic transport mechanisms like ABC transporters and a comparative operational blueprint evaluating physical–chemical conventional remediation techniques against advanced in situ and ex situ biotechnological approaches, including biochar assistance, microbial engineering, rhizosphere synergies, and engineered nanomaterials. By systematically linking industrial source dynamics with cellular toxicological mechanisms and field-scale engineering feasibility, this review establishes an actionable roadmap for future genetic, agronomic, and management interventions aimed at securing global food. Full article

Existing anti-aging drugs are often limited by toxicity and resistance. In contrast, natural substances derived from food resources, edible plants, and agricultural by-products offer advantages such as low toxicity and suitability for dietary intake. Utilizing these resources aligns with sustainable development goals by promoting the valorization of food waste and functional food development; however, their complex composition makes traditional discovery inefficient and resource-intensive. Machine learning (ML) provides a powerful, sustainable in silico solution. By analyzing vast datasets, computational models can rapidly screen thousands of candidates, significantly reducing the chemical waste and time associated with traditional wet-lab screening. This review focuses on the current status of food-derived anti-aging bioactives and the emerging ML-based perspectives in this field. Key natural compounds and plant extracts are discussed, highlighting their dietary origins and mechanisms. Furthermore, we explore how advanced algorithms accelerate the identification of novel bioactives. Importantly, we address current translational gaps, including the need for explainable AI, ADME (Absorption, Distribution, Metabolism, and Excretion) prediction, and the standardization of complex mixtures. Overcoming these bottlenecks is essential for the sustainable development of effective, food-based anti-aging ingredients. Full article

Artificial soils derived from coal combustion by-products and industrial waste have been successfully used for mine spoil reclamation; however, their ecological risk and toxic element migration in the soil–plant system have not been assessed. The objective of this study was to evaluate the ecological risks in soil substitute covers after five years of their exposition, using the ecological risk factor (ERⁱ), potential ecological risk index (PERI) and geoaccumulation index. The modified BCR-sequential extraction method was applied to determine the chemical partitioning of the most toxic heavy metals (Cd, Cr, Cu, Ni, Pb, Zn). Additionally, the bioconcentration and translocation factors were used to assess the uptake of toxic elements by Phragmites australis. Findings from PERI indicate a moderate risk (239 and 258), mainly associated with moderate and considerable ERⁱ for Cd and Hg, respectively. The other toxic metals are associated with a low risk (ERⁱ < 40). Sequential extraction results showed the lowest concentrations of heavy metals in F1 fraction (0–30%) and increased in subsequent fractions: F2 (1–43%), F3 (10–62%) and F4 (10–89%). The calculated BCF values were below 1, indicating that the concentration of toxic metals in plants was lower than that in the soil substitute. The only exception was observed for Mn and Sn (BCF > 1). The results suggest that the tested soil substitutes are suitable for the reclamation of post-mining areas and may support sustainable biomass production. However, due to industrial atmospheric deposition and ecological risk associated with selected trace elements, continued monitoring of toxic metals is recommended. Full article

The use of nanoscale materials has expanded rapidly in recent decades, with titanium dioxide (TiO₂) nanoparticles among the most widely produced. Their increasing environmental release raises concerns about ecosystem-level effects. A key mechanism of toxicity is the generation of reactive oxygen species (ROS), although these effects strongly depend on particle properties, including crystalline form, size, morphology, surface characteristics, and exposure conditions. Here, we assessed and compared the ecological impacts of anatase and rutile TiO₂ nanoparticles across prokaryotic and eukaryotic systems, including aquatic microbial communities, microbial cultures, plant bioassays (Sinapis alba, Triticum aestivum), the SOS Chromotest, and zebrafish (Danio rerio) assays. Nano-TiO₂ exposure markedly restructured freshwater microbial communities by suppressing sensitive taxa (e.g., Actinomycetota, Flavobacterium, and Limnohabitans) while enriching more tolerant genera such as Pseudomonas, Sediminibacterium, Haliscomenobacter, and Hydrogenophaga. These shifts likely reflect differences in cell-envelope structure, biofilm formation, and antioxidant capacity. The two investigated TiO₂ nanoparticle types showed distinct biological effects: rutile was associated with more pronounced microbial community shifts and bacterial cell damage, whereas anatase caused stronger responses in plant assays, particularly by impairing hypocotyl growth and plant water balance. Besides the limited acute genotoxicity revealed by the SOS Chromotest, TiO₂ nanoparticles did not significantly affect survival or final larval body length in the zebrafish embryo assay under the tested conditions; however, the hatching delay observed at the highest concentration indicated a sublethal developmental effect. Overall, our results show that TiO₂ nanoparticle toxicity cannot be generalized across biological systems and suggest that biological responses depend on the combined influence of particle characteristics and organism-specific structural and physiological traits. Full article

Objectives: Malaria remains a major global health burden, particularly in endemic regions such as Djibouti, where Plasmodium falciparum and Plasmodium vivax co-circulate, complicating disease control strategies. Increasing resistance to current antimalarial drugs reduces treatment effectiveness and highlights the urgent need for new, safe, and affordable therapeutic agents. This study aimed to identify potential inhibitors from Djiboutian medicinal plants using an integrated in silico approach targeting key proteins from both parasite species. Methods: A library of 222 phytoconstituents was screened against Plasmodium vivax FK506-binding protein 35 (PDB ID: 3IHZ) and Plasmodium vivax dihydrofolate reductase–thymidylate synthase (PDB ID: 1J3K) using molecular docking. Top-ranked compounds were further analyzed for binding interactions and evaluated for drug-likeness and pharmacokinetic properties using QikProp in Maestro v11.5. Selected protein–ligand complexes were subjected to 100 ns molecular dynamics simulations, and their stability was assessed using multiple descriptors, including structural deviation, flexibility, compactness, solvent exposure, and hydrogen bond persistence. Results: Several phytoconstituents exhibited strong binding affinities, with docking scores ranging from −6.09 to −7.54 kcal/mol, outperforming the reference drug artemisinin. Interaction analysis revealed key hydrogen bonds and hydrophobic contacts with essential active-site residues. ADMET predictions indicated favorable pharmacokinetic profiles, including high oral absorption, good membrane permeability, and low predicted toxicity. Molecular dynamics simulations demonstrated stable behavior for most complexes, with compound 121 showing enhanced stability in the 1J3K system and compound 123 exhibiting consistent dynamic stability in the 3IHZ system. In contrast, compound 82 displayed greater structural fluctuations despite maintaining stable hydrogen bond interactions. Conclusions: The integration of molecular docking, ADMET prediction, and molecular dynamics simulations identified compounds 121 and 123 as the most promising antimalarial candidates, exhibiting an optimal balance of binding affinity, favorable pharmacokinetic properties, and dynamic stability. These findings highlight the potential of Djiboutian medicinal plants as a valuable source of novel antimalarial agents and provide a strong computational foundation for future experimental validation. Full article

Background/Objectives: Triple-negative breast cancer (TNBC) is one of the most aggressive breast cancer subtypes and remains associated with limited therapeutic options and high systemic toxicity from conventional chemotherapy. Ipomoea pes-caprae is a coastal medicinal plant traditionally consumed in Mexico for inflammatory and renal disorders and contains bioactive metabolites with reported antioxidant and pharmacological properties. However, its antitumoral activity and systemic safety profile remain poorly understood. This study aimed to characterize the phytochemical composition, antioxidant capacity, antitumoral activity, and toxicity of a traditionally prepared aqueous infusion of I. pes-caprae leaves (IPCAE). Methods: IPCAE was characterized using phytochemical screening and complementary instrumental analyses. Antioxidant activity was evaluated using the DPPH assay. A randomized preclinical study was performed in mice bearing MDA-MB-231 xenografts treated with IPCAE, cisplatin, or saline control. Results: The infusion showed measurable antioxidant activity (72.25 ± 1.25% DPPH inhibition at 1 mg/mL) and a total polyphenol content of 7.29 µg/mg gallic acid equivalents. Phytochemical screening revealed abundant flavonoids and reducing sugars, with moderate saponin content. In vivo, IPCAE produced only a transient and non-significant trend toward slower tumor progression compared with control (p = 0.214) and cisplatin (p = 0.377). However, marked systemic toxicity was observed, including severe thoracic dermal lesions in 40% of animals and 70% mortality by day 15. Survival was significantly reduced compared with control and cisplatin groups (p < 0.001). Conclusions: Although IPCAE exhibited antioxidant activity, no statistically significant antitumoral effect was observed under the evaluated conditions. Furthermore, repeated oral administration resulted in marked systemic toxicity, characterized by visible dermal lesions, clinical deterioration, and increased mortality. Therefore, the present findings do not support the use of the evaluated crude preparation as an anticancer intervention. Future studies should focus on detailed toxicological characterization, bioassay-guided fractionation, dose optimization, and identification of the individual metabolites responsible for the observed biological effects. The antioxidant activity demonstrated in this study should be interpreted independently from antitumoral activity, as no causal relationship between these findings was established. Full article

The aim of this study was to examine the hepatoprotective activity of multicomponent mixtures of natural origin in the BALB/C mouse model (n = 59), with acute direct toxic liver injury (DTLI) induced by the administration of streptozotocin (STZ) (100 mg/kg) in combination with a high-fat and high-fructose diet (HFFD). The hepatoprotective activity of activated hydrolytic lignin (Bp-Cx-1), methanolic fraction of Bp-Cx-1 (Bp-Cx-M) and isoflavones from kudzu Pueraria lobata roots (IFL) were evaluated on molecular level using mass spectrometry (MS)-based omics technologies. Untargeted label-free DIA quantitation resulted in 7214 protein groups identification (FDR 1%) after filtering across 40 liver tissue extracts. All treatment groups were closer to the control samples on the liver proteomic landscape compared to the untreated DTLI group, with the best results shown for the Bp-Cx-M and IFL groups. In order to identify differences between specific groups, we applied the post hoc Dunn’s test and used Hedges’ g as the effect size metric, revealing 64 proteins that tended to return to their normal level after treatment. In-depth proteomic liver tissue analysis enabled us not only to reveal the main pathways such as inflammation and oxidative stress, which are in a good agreement with DTLI and non-alcoholic liver disease pathophysiology, but also to evaluate hepatoprotective activity of multicomponent mixtures of natural origin containing polyphenols and mostly associated with protein metabolism (e.g., PSMD7, HCFC1) and deubiquitination pathways (e.g., UCHL3). It is worth noting that the Bp-Cx-1 isolated methanol fraction (Bp-Cx-M) demonstrated a pronounced increased hepatoprotective activity compared to the parent material due to the enrichment with active components such as polyphenols. Consistent with the proteomic findings of restored ubiquitin–proteasome function, assessment by comet assay revealed that treatments with Bp-Cx-M and IFL significantly reduced DNA damage by 50% compared to the untreated DTLI group. The developed MS-based multi-omics approach may be implemented for the robust and high-throughput screening method during assessment of new hepatoprotective agents of synthetic or natural origin. Full article

Cancer remains one of the most frightening global health challenges, contributing substantially to morbidity and mortality across diverse populations. In recent years, naturally derived compounds have attracted considerable attention due to their potential therapeutic efficacy and fewer adverse effects. Among these, the flavokawain subclass of chalcones, comprising Flavokawains A, B, and C, obtained from various plant sources, has emerged as a promising group of bioactive phytochemicals exhibiting a broad spectrum of pharmacological activities, with notable anticancer potential. This review critically compiles and evaluates the existing preclinical evidence regarding the anticancer mechanisms of flavokawains across various cancer models. It was found that these compounds have significant potential to inhibit cancer cell proliferation, induce apoptosis, disrupt cell-cycle progression, and modulate multiple molecular pathways implicated in tumorigenesis, including phosphoinositide 3 kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), extracellular-signal regulated kinase/c-Jun N-terminal kinase/mitogen-activated protein kinase (ERK/JNK/MAPK) and so on. Importantly, flavokawains exert significant modulatory effects within the tumor microenvironment by suppressing angiogenesis through downregulation of vascular endothelial growth factor (VEGF) and Angiopoietin-1 (Ang-1), attenuating epithelial-mesenchymal transition via restoration of E-cadherin and suppression of vimentin and Snail1, inhibiting matrix metalloproteinase (MMP)-mediated extracellular matrix remodeling, and disrupting cancer stem cell (CSC)-supportive niches. Preclinical toxicity profiles suggest a favorable safety margin, though further investigation is required to fully elucidate their therapeutic index. Due to their multifaceted mechanisms of action and selective cytotoxicity toward cancer cells, flavokawains are considered promising preclinical candidates for development as adjuncts or alternatives to conventional chemotherapeutic agents. Full article

Colorectal cancer (CRC) remains one of the leading causes of cancer-related mortality worldwide, and the efficacy of conventional chemotherapy is frequently limited by systemic toxicity, chemoresistance, and tumor recurrence. Natural products derived from marine algae and plants have attracted increasing interest as multitarget adjuvant agents capable of modulating apoptosis, oxidative stress, and tumor-associated signaling pathways. In the present study, we evaluated the anticancer activity of commercially available formulations enriched in fucoxanthin, fucoidan, tocotrienols, astaxanthin, and apple polyphenols, either alone or in combination with doxorubicin (DOX), using two-dimensional and three-dimensional colorectal cancer models. Initial IC₅₀ screening in ovarian (OVCAR3), prostate (PC3), colorectal (Caco2 and HT-29), and non-tumorigenic colon epithelial cells demonstrated that formulations 2.1 and 10.0 exhibited the most relevant cytotoxic activity, particularly in colorectal cancer cells. Combined treatments with DOX significantly reduced cell viability compared to individual treatments, particularly in Caco2 cells, where viability decreased to approximately 10% under combined exposure conditions. Mechanistically, combined treatments enhanced caspase-3/7 activation in both Caco2 and HT-29 cells, indicating apoptosis-associated effects. These findings were further supported in three-dimensional spheroid models, where supplement combinations impaired spheroid expansion, induced apoptotic AO/EB staining patterns, and reduced HT-29 spheroid growth by approximately 30–35%, reaching inhibitory effects comparable to DOX alone. Collectively, these results suggest that plant- and algae-derived formulations enriched in antioxidant bioactives may enhance chemotherapy-associated antitumor responses through apoptosis-related mechanisms and modulation of tumor-like growth behavior. The present findings support the further exploration of natural-product-based adjuvant strategies in colorectal cancer therapy using more clinically representative chemotherapeutic schemes and in vivo models. Full article

Pulmonaria rubra (Boraginaceae) is a widely distributed plant in Bulgaria, yet its phytochemical profile and therapeutic potential have remained unexplored. P. rubra methanol extract (PRE) was evaluated through phytochemical profiling and in vitro neuroprotective and antioxidant assays. Rat brain synaptosomes, mitochondria and microsomes were treated with PRE alone, and in combination with 6-hydroxydopamine and tert-butyl hydroperoxide as toxic agents. The extract exhibited concentration-dependent protective effects in all subcellular models. Additionally, it was tested on hMAOA/B and different isoforms of CYP450 enzymes, but it did not show any activity in the tested conditions. In the UHPLC-HRESIMS analysis, 26 secondary metabolites were identified, mainly hydroxycinnamic acids and caffeoyl oligomers, flavonoids, a lignan (globoidnan A), and the terpenoid glycoside roseoside. Seven compounds were identified via UHPLC-UV method using reference compounds: rosmarinic acid, rutin, quercetin-3-O-glucoside, astragalin, apigenin-7-O-glucoside, apigenin-7-O-glucuronide and alcesefoliside, with the latter two being reported for the first time in genus Pulmonaria. The quantity of rosmarinic acid in PRE was 4.35%, distinguishing the compound as the main bioactive molecule in the species. Characterized by its high content of rosmarinic acid, P. rubra represents a highly viable candidate for subsequent development into standardized phytopharmaceuticals targeting oxidative stress-related neurodegenerative diseases. Full article

Rising salt concentration in water induces osmotic stress and ionic toxicity, compromising photosynthesis, growth, and survival of threatened species such as Paubrasilia echinata and highlighting the need for stress-mitigating compounds such as salicylic acid. This study evaluated the effect of salicylic acid on the morphophysiological responses of P. echinata seedlings irrigated with saline water. Treatments were arranged in a 2 × 3 factorial scheme, with two electrical conductivity levels of irrigation water (0.5 and 6.0 dS m⁻¹) and three salicylic acid concentrations (0, 2, and 3 mM), randomized across 24 experimental plots containing five plants each in a randomized complete block design. Analyses included growth, relative water content, chlorophyll indices and fluorescence of seedlings. Irrigation water with an electrical conductivity of 6.0 dS m⁻¹ reduced leaf number by 9.09% and PSII efficiency by 26.94%. Under saline conditions, salicylic acid at 2 and 3 mM increased root dry matter by 49.28% and 60.29%, respectively. The highest total chlorophyll index (79.03) was obtained at 2 mM, whereas leaf area peaked at 734.74 cm² per plant at 3 mM. Salicylic acid enhances salt tolerance in P. echinata. At 2 mM, it improves seedling morphophysiological traits and may support restoration in salinized sites. Full article

Background: Alcohol use is a major global health burden and is causally linked to several wholly alcohol-attributed conditions, including alcohol use disorder (AUD) and alcohol-associated liver disease (ALD). Current therapeutic options remain limited. Dihydromyricetin (DHM), a plant-derived flavonoid with antioxidant and anti-inflammatory properties, has emerged as a potential candidate for mitigating alcohol-induced toxicity. This systematic review aimed to comprehensively evaluate the therapeutic effects of DHM across alcohol-related conditions. Methods: A systematic literature search was conducted in PubMed from inception through December 2025 for studies investigating the effects of DHM or DHM-containing extracts on alcohol-related outcomes. Both preclinical (in vitro and in vivo) and clinical studies were considered. Study quality was assessed qualitatively due to heterogeneity precluding use of a standardized risk-of-bias tool. Results were synthesized narratively by outcome category; meta-analysis was not performed. This review was unregistered with no prior protocol. Results: A total of 22 studies were included, comprising 8 in vitro, 17 in vivo, and 2 clinical studies, with some studies contributing data to more than one category. Across models, DHM consistently attenuated ethanol-induced cytotoxicity, oxidative stress, inflammation, and hepatic steatosis. DHM improved liver injury biomarkers (e.g., AST and ALT), enhanced antioxidant defenses, and modulated key signaling pathways including Nrf2 and AMPK. Additionally, DHM supported mitochondrial function and intestinal barrier integrity. However, findings related to ethanol metabolism and neurobehavioral outcomes were inconsistent. Clinical evidence was limited to two small trials using Hovenia dulcis extracts, which demonstrated reductions in hangover severity and selected inflammatory markers but did not directly evaluate isolated DHM. Conclusions: DHM demonstrates robust preclinical efficacy in mitigating alcohol-induced injury, particularly in hepatic outcomes. Despite promising mechanistic and experimental evidence, clinical data remain limited. The certainty of evidence is constrained by preclinical study heterogeneity, the absence of formal risk-of-bias assessment, and the lack of clinical trials using isolated DHM. Well-designed clinical trials using standardized DHM formulations are needed to establish its complete therapeutic potential in alcohol-related disorders. Full article

Atmospheric pressure non-thermal plasma (APNTP) is an emerging technology with demonstrated potential for mitigating diverse environmental stresses in agriculture and animal health. This review synthesizes current evidence on plasma-mediated stress regulation in plants and animals. For plants, APNTP enhances tolerance to drought, salinity, temperature extremes, heavy-metal toxicity, and pathogen infections through activation of antioxidant systems, stress-responsive gene expression, and adaptive signaling pathways. For animals, APNTP promotes wound healing, microbial disinfection, reproductive health, and environmental pollutant degradation via modulation of oxidative balance, inflammatory responses, and cellular repair mechanisms. However, most reported effects to date are based on laboratory-scale studies under controlled conditions, and critical gaps remain in dose-dependent toxicity profiles, protocol standardization, and long-term safety data. We highlight future priorities including mechanistic studies, parameter optimization, safety assessment, and scalability evaluation. This review provides a comprehensive framework for advancing APNTP applications toward sustainable agriculture and improved animal welfare. Full article

The review evaluates current clinical and epidemiological evidence regarding the use of plant-derived compounds in pediatric practice. Data from randomized controlled trials indicate symptomatic efficacy of selected agents—particularly in acute respiratory infections—alongside generally favorable safety profiles when standardized preparations are used. Emerging research also explores applications in neurodevelopmental disorders, gastrointestinal conditions, and dermatology, and as supportive therapy in pediatric oncology. However, variability in product quality, limited pediatric-specific trials, potential toxicity, and regulatory inconsistencies remain significant challenges. The integration of phytotherapy into pediatric care therefore requires rigorous study design, careful safety monitoring, and clear quality standards to ensure an evidence-based risk–benefit balance. Full article

The growing demand for efficient and sustainable materials for air purification has stimulated interest in activated carbons derived from renewable biomass resources. In this study, activated carbons were prepared from Rice Husk, Wheat Straw, Sawdust, and Walnut shells and systematically investigated as sorbents for toxic gases and volatile organic compounds. The materials were characterized using nitrogen and water vapor sorption isotherms, scanning electron microscopy, thermogravimetric analysis, Fourier-transform infrared spectroscopy, energy-dispersive X-ray and XPS analysis to evaluate their textural properties, morphology, thermal stability, and surface chemistry. The results showed that the precursor type strongly influences the pore structure and functional group composition of the activated carbons. Wheat straw and Rice Husk-derived activated carbons exhibited the highest total pore volume and a well-developed porous structure, together with a high content of oxygen- and silicon-containing elements. Gas breakthrough experiments with different probes showed that Wheat Straw-derived activated carbon excels in non-polar VOC—cyclohexane removal due to its highly microporous structure. In contrast, Rice Husk-derived activated carbon displays strong affinity toward inorganic gases such as NH₃ and, after urea modification, achieves enhanced performance for SO₂. These results underscore the versatility and practical applicability of carbon materials obtained from plant residues. Full article