Search Results (1,390)

This article presents the potential use of a humic agent called ‘Superhumate’, obtained from weathered coal from the Shubarkol deposit in Kazakhstan. The experiment was conducted using model solutions and surface mine water samples from the “Degelen” site at the Semipalatinsk Test Site. The adsorption of heavy metals and toxic elements using the “Superhumate” agent was carried out under dynamic conditions using a chromatographic column. Tests were conducted at a natural pH range of 5–8 (mine waters) and with a model solution at pH 1.7. Assessing the sorption efficiency of this preparation revealed that at pH 1.7, the agent does not adsorb elements such as Cd, Cu, Pb, and Zn. Under dynamic experimental conditions, using the preparation for mine waters at natural pH levels (pH 5–8), elements such as Be, Sr, Mo, Cd, Cs, Zn, and U were efficiently adsorbed at levels of 60–95%. The sorption efficiency of Pb ions was found to be almost independent of pH. The experimental results obtained with mine water samples indicate that alkaline solutions have the highest sorption efficiency, with pH ≥ 7, which is attributed to the solubility of the agent. Full article

Background/Objectives: High-risk neuroblastoma patients are treated with approved anti-ganglioside GD2 antibodies of moderate (dinutuximab beta; DB) and higher binding affinity (naxitamab; NAXI). We evaluated the functional potency of DB compared to NAXI and investigated the target-mediated drug disposition (TMDD). Methods: Tumor spheroids were generated from neuroblastoma cells with varying GD2 expression, stably expressing iRFP680 as a viability marker. Antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) were assessed in a long-term life-cell viability assay using serial dilutions of the GD2 antibodies. Binding activity was determined by flow cytometry. Processes involved in TMDD were analyzed, including antibody binding to dead tumor cells and to soluble GD2 (sGD2), antibody internalization into tumor and immune cells and the impact of sGD2 on DB and NAXI-mediated ADCC. Results: DB and NAXI mediated a concentration-dependent ADCC response against GD2-positive spheroids and no response against GD2-negative spheroids. DB showed a significantly higher ADCC potency than NAXI in all GD2-positive spheroid models. Binding activity of DB and NAXI was not significantly different. However, the decrease of anti-GD2 antibody binding to viable GD2-positive tumor cells following co-incubation with dead GD2-positive tumor cells or sGD2 was significantly higher for NAXI than DB. Additionally, we found an increased internalization of NAXI compared to DB by tumor cells and particularly CD64+ monocytes. Finally, sGD2 impaired NAXI-mediated ADCC to a significantly greater extent than DB-mediated ADCC. Conclusions: DB has a higher ADCC potency over NAXI at clinically relevant concentrations, attributed to stronger TMDD effects of NAXI compared to DB. Full article

Cetraria islandica (L.) Ach. (CI) is a lichen from the Parmeliaceaea family used in medicine. However, the low solubility of CI secondary metabolites in water limits the application of lichen extract and compounds. It prompted us to study the systems of cyclodextrins (CDs) (β-CD, γ-CD, HP-β-CD, and HP-γ-CD) with the CI acetone or CI methanol extracts prepared using grinding and solvent evaporation methods. The content of fumarprotocetraric acid (FPCA), a key CI metabolite, was quantified using HPLC. CD–extract systems were characterized by X-ray powder diffraction (XRPD) and Fourier-transform infrared (FTIR) spectroscopy. Biological activity was evaluated using cell-free assays: a Folin–Ciocalteu analysis, DPPH test, acetylcholinesterase, butyrylcholinesterase, and tyrosinase inhibitions. Dissolution profiles were also assessed. The best biological and physicochemical results were obtained for systems prepared with HP-β-CD and HP-γ-CD via solvent evaporation, showing higher activity and enhanced FPCA release compared to the pure extracts. To the best of our knowledge, this is the first study to report the preparation and characterization of CD-based systems with CI extracts. The obtained results encourage us to continue our research on CI to improve the physicochemical properties of its active compounds. Full article

Graphene quantum dots (GQDs) obtained by microwave-induced pyrolysis of glutamic acid and triethylenetetramine (trien) are fairly stable, emissive, water-soluble, and positively charged nano-systems able to interact with negatively charged meso-tetrakis(4-sulfonatophenyl) porphyrin (TPPS₄). The stoichiometric control during the preparation affords a supramolecular adduct, GQDs@TPPS₄, that exhibits a double fluorescence emission from both the GQDs and the TPPS₄ fluorophores. These supramolecular aggregates have an overall negative charge that is responsible for the condensation of cations in the nearby aqueous layer, and a three-fold acceleration of the metalation rates of Cu²⁺ ions has been observed with respect to the parent porphyrin. Addition of various metal ions leads to some changes in the UV/Vis spectra and has a different impact on the fluorescence emission of GQDs and TPPS₄. The quenching efficiency of the TPPS₄ emission follows the order Cu²⁺ > Hg²⁺ > Cd²⁺ > Pb²⁺ ~ Zn²⁺ ~ Co²⁺ ~ Ni²⁺ > Mn²⁺ ~ Cr³⁺ >> Mg²⁺ ~ Ca²⁺ ~ Ba²⁺, and it has been related to literature data and to the sitting-atop mechanism that large transition metal ions (e.g., Hg²⁺ and Cd²⁺) exhibit in their interaction with the macrocyclic nitrogen atoms of the porphyrin, inducing distortion and accelerating the insertion of smaller metal ions, such as Zn²⁺. For the most relevant metal ions, emission quenching of the porphyrin evidences a linear behavior in the micromolar range, with the emission of the GQDs being moderately affected through a filter effect. Deliberate pollution of the samples with Zn²⁺ reveals the ability of the GQDs@TPPS₄ adduct to detect sensitively Cu²⁺, Hg^2+, and Cd²⁺ ions. Full article

Sepsis represents a major cause of mortality, especially among patients with liver cirrhosis, who are at increased risk due to immune dysfunction, gut-derived bacterial translocation, and altered hepatic metabolism. Traditional biomarkers such as C-reactive protein (CRP), procalcitonin (PCT), and interleukin-6 (IL-6) often have reduced diagnostic reliability in this subgroup, due to impaired liver and renal function. Presepsin, a soluble fragment of CD14 released during phagocytic activation, has emerged as a promising biomarker for early sepsis detection. This systematic review explores the diagnostic and prognostic utility of presepsin in cirrhotic and non-cirrhotic patients with suspected infection. Data from multiple clinical studies indicate that presepsin levels correlate with infection severity and clinical scores such as SOFA and APACHE II. In cirrhotic patients, presepsin demonstrates superior sensitivity and specificity compared to conventional biomarkers, maintaining diagnostic value despite hepatic dysfunction. Its utility extends to differentiating bacterial infections from fungal infections and monitoring treatment response. While preliminary evidence is compelling, further prospective, multicenter studies are required to validate its integration into standard care algorithms. Presepsin may become a valuable addition to clinical decision-making tools, particularly in hepatology-focused sepsis management. Full article

Monkeypox virus (MPXV) has caused 148,892 confirmed cases and 341 deaths from 137 countries worldwide, as reported by the World Health Organization (WHO), highlighting the urgent need for effective vaccines to prevent the spread of MPXV. Traditional vaccine development is low-throughput, expensive, time consuming, and susceptible to reversion to virulence. Alternatively, a reverse vaccinology approach offers a rapid, efficient, and safer alternative for MPXV vaccine design. Here, MPXV proteins associated with viral infection were analyzed for immunogenic epitopes to design multi-epitope vaccines based on B-cell, CD4+, and CD8+ epitopes. Epitopes were selected based on allergenicity, antigenicity, and toxicity parameters. The prioritized epitopes were then combined via peptide linkers and N-terminally fused to various protein adjuvants, including PADRE, beta-defensin 3, 50S ribosomal protein L7/12, RS-09, and the cholera toxin B subunit (CTB). All vaccine constructs were computationally validated for physicochemical properties, antigenicity, allergenicity, safety, solubility, and structural stability. The three-dimensional structure of the selected construct was also predicted. Moreover, molecular docking and molecular dynamics (MD) simulations between the vaccine and the TLR-4 immune receptor demonstrated a strong and stable interaction. The vaccine construct was codon-optimized for high expression in the E. coli and was finally cloned in silico into the pET21a (+) vector. Collectively, these results could represent innovative tools for vaccine formulation against MPXV and be transformative for other infectious diseases. Full article

Background/Objectives: Enriched oral nutritional supplementation (ONS) has been shown to increase muscle mass in cancer patients. This study aims to identify the immunomodulatory effects and predictive biomarkers associated with this intervention. Methods: The soluble levels of 92 immune- and oncology-related mediators were determined before and after an intervention (8 weeks) in 28 patients with cancer receiving either a standard (n = 14) or an enriched ONS (n = 14) using the Olink proteomics analysis pipeline (Olink^® Target 96 Immuno-Oncology panel (Uppsala, Sweden)) Results: Patients receiving enriched ONS experienced an average weight gain of 1.4 kg and a muscle mass increase of 2.2 kg after 8 weeks, both statistically significant (p < 0.05), while no such improvements were observed in the standard ONS group. Inflammatory markers TRAIL and LAMP3 were significantly reduced, along with an increase in Gal-1, suggesting lower inflammation and enhanced myogenic differentiation. However, patients who failed to gain muscle mass with the enriched formula showed a more aggressive inflammatory profile, characterized by higher serum levels of soluble MUC16, ARG, and IL12RB1. Interestingly, muscle mass gain could be predicted before the intervention, as responders had lower baseline levels of PGF, CD28, and IL12RB1. These differences were specific to recipients of the enriched ONS, confirming its immunomodulatory effects. Conclusions: Our findings support the use of enriched oral nutritional supplementation (ONS) as an effective strategy not only to enhance caloric and protein intake but also to promote anabolism and preserve muscle mass in cancer patients. The identification of immune profiles suggests that specific biomarkers could be used to predict which patients will benefit most from this type of intervention. This may allow for the implementation of personalized immunonutrition strategies that optimize resource allocation and improve clinical outcomes, particularly in vulnerable populations at risk of cachexia. Full article

Although platelets have been traditionally thought of to be essential hemostasis mediators, new research shows how important they are for controlling cellular oxidative stress, inflammatory processes, and immunological responses—particularly during major surgery on the abdomen. Perioperative problems are largely caused by the continually changing interaction of inflammatory cytokines, the formation of reactive oxygen species (ROS), and platelet activation. The purpose of this review is to summarize the most recent data regarding the complex function of platelets in abdominal surgery, with an emphasis on how they interact with inflammation and oxidative stress, and to investigate the impact on postoperative therapy and subsequent studies. Recent study data on platelet biology, redox signals, surgical stress, and antiplatelet tactics was reviewed in a systematic manner. Novel tailored therapies, perioperative antiplatelet medication, oxidative biomarkers of interest, and platelet-derived microscopic particles are important themes. In surgical procedures, oxidative stress dramatically increases the reactive capacity of platelets, spurring thromboinflammatory processes that affect cardiac attacks, infection risk, and recovery. A number of biomarkers, including soluble CD40L, thromboxane B2, and sNOX2-derived peptide, showed potential in forecasting results and tailored treatment. Antiplatelet medications are still essential for controlling risk factors for cardiovascular disease, yet using them during surgery necessitates carefully weighing the risks of thrombosis and bleeding. Biomarker-guided therapies, antioxidant adjuncts, and specific platelet inhibitors are examples of evolving tactics. In abdominal procedures, platelets strategically operate at the nexus of oxidative stress, inflammatory processes, and clotting. Improved patient classification, fewer problems, and the creation of individualized surgical care strategies could result from an increased incorporation of platelet-focused tests and therapies into perioperative processes. To improve clinical recommendations, subsequent studies may want to focus on randomized studies, biomarker verification, and using translational approaches. Full article

Soluble CD40 ligand (sCD40L) is a molecule known for its thromboinflammatory properties and may act as a biomarker for platelet activation. Platelets are the principal producers of sCD40L, which is recognized for its impact on platelet function. However, its contribution to the platelet hyperreactivity observed in SARS-CoV-2 infection remains poorly understood. During viral infection, platelets function as crucial intermediaries, engaging with both viruses and leukocytes; and serve as a substantial source of inflammatory mediators, promoting thromboinflammation and immunothrombosis. While platelet hyperactivation is associated with the severity and mortality of COVID-19, the precise function of sCD40L in this setting remains inadequately defined. This study examined the role of platelet-derived sCD40L in platelet activation, aggregation, and thrombosis associated with COVID-19. Platelets from blood samples of 160 patients—102 with non-severe cases and 58 with severe cases—demonstrated heightened activation and aggregation, as well as elevated sCD40L release. In a mouse thrombosis model, sCD40L intensified thrombus development. These findings underscore the essential function of platelet-derived sCD40L in the pathophysiology of COVID-19 and endorse the therapeutic potential of targeting CD40L-mediated pathways to mitigate thromboinflammatory consequences. Full article

Background: Oral squamous cell carcinoma (OSCC) is a common head and neck cancer with low survival rates, especially in advanced stages, despite improved therapies. New developments show that immune checkpoint inhibitors (ICIs) are promising treatment options. A better understanding of immune suppression in OSCC could enable new therapeutic approaches and effective ICI combinations. Methods: The aim of this cross-sectional study was to investigate the significance of the differential expression of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), CD28 and their ligands CD80 and CD86 for the diagnosis and treatment of OSCC. To this end, mRNA expression was analysed by RT-PCR and compared in 65 healthy oral mucosa samples (NOM) and 104 OSCC samples. Results: The expression of CTLA-4 (a soluble and membrane-bound isoform) was increased in OSCC by 1.72-fold (p = 0.004) and 6.88-fold (p < 0.001), respectively. There was no significant difference for CD28 (p = 0.283), nor for the soluble isoform of CD86 (p = 0.845). The membrane isoform of CD86 was increased in OSCC by a factor of 1.39 (p = 0.009) and CD80 by 6.11-fold (p < 0.001). Conclusions: The results show a significant association between CTLA-4, CD80 and membrane-bound CD86 expression and diagnosis. They could improve diagnostics in multi-marker approaches and serve as therapeutic targets for ICI strategies. In particular, the data indicate a stronger immunosuppressive role of CD80 compared to CD86 in a tumor tissue context, suggesting the exploration of anti-CTLA-4 and anti-CD80 antibody combinations in animal models. Full article

This study evaluated the influence of different male date palm cultivars, distinguished by their chloroplast haplotypes, on pollen quality, pollination efficiency, metaxenia effects, and gene expression during fruit development. Chloroplast DNA analysis of 37 male trees revealed multiple haplotypes, from which cultivars B25, P8, C22, and B46 were selected for further investigation. Pollen viability varied significantly among cultivars, with P8 and B25 exhibiting the highest germination rates and pollen tube elongation, while C22 showed the lowest. These differences correlated with pollination success: P8 and B25 achieved fertilization rates near 99%, whereas C22 remained below 43%. Pollination outcomes also varied in fruit traits. Despite its low pollen performance, C22 induced the production of larger fruits at the Bleh (Kimri) stage, potentially due to compensatory physiological mechanisms. Phytochemical profiling revealed significant cultivar effects: fruits from B25-pollinated trees had with lower moisture and polyphenol content but the higher sugar levels and soluble solids, suggesting accelerated maturation. Ripening patterns confirmed this finding, with B25 promoting the earliest ripening and B46 causing the most delayed. Gene expression analysis supported these phenotypic differences. Fruits pollinated by P8, B25, and B46 exhibited elevated levels of cell-division-related transcripts, particularly the PdCD_1 gene (PDK_XM_008786146.4, a gene encoding a cell division control protein), which was most abundant in P8. In contrast, fruits from C22-pollinated trees had the lowest expression of growth-related genes, suggesting a shift toward cell expansion rather than division. Overall, the results show the critical role of male genotype in influencing fertilization outcomes and fruit development, offering valuable insights for targeted breeding strategies at enhancing date palm productivity and fruit quality. Full article

Suaeda salsa is relatively tolerant to cadmium (Cd) contamination. In order to investigate the bioaccumulation and stress responses of S. salsa under chronic exposure, we explored the growth, accumulation, and changes in antioxidant enzymes and glutathione (GSH) under different Cd concentrations over a 30-day soil culture experiment. Seedling height and weight in the 13.16 mg/kg Cd group were 13.26 cm and 0.21 g, significantly higher than the control group. Growth was significantly inhibited under high Cd concentration exposure, with a seedling and root length of 9.65 cm and 3.77 cm. The Cd concentration in all tissues was positively related to Cd treatment concentration, with the Cd contents in the roots being higher than in the other tissues. At a subcellular level, Cd was mainly concentrated in the cell walls, organelles, and soluble components within the range of 0.05–8.29, 0.02–2.40 and 0.08–1.35 μg/g, respectively. The accumulation of Cd in the roots tracked its proportion in the cell walls. The malondialdehyde (MDA) content of the plant tissues increased with increasing Cd concentration, indicating that Cd stress caused oxidative damage. The GSH content increased with increasing Cd concentration, with maximum values of 0.515 μmol/g in the stem in the 66.07 mg/kg Cd group. The catalase (CAT), superoxide dismutase (SOD), and peroxidase (POD) activity showed different change trends under Cd exposure. The results in this study could provide useful information on the tolerance mechanism of Cd in S. salsa, which provides information for exploiting S. salsa as a candidate for phytoremediation of Cd contamination. Full article

Cyclodextrins (CDs) are cyclic oligosaccharides capable of forming inclusion complexes with various guest molecules, enhancing solubility, stability, and bioavailability. This review outlines the structural features of native CDs and their chemically modified derivatives, emphasizing the influence of functionalization on host–guest interactions. Synthetic approaches for CD derivatization are summarized, with attention to recent developments in stimuli-responsive systems and targeted drug delivery. Analytical techniques commonly employed for characterizing CD complexes, such as spectroscopy, thermal analysis, and molecular modeling, are briefly reviewed. Applications in pharmaceutical formulations are discussed, including inclusion complexes, CD-based conjugates, and nanocarriers designed for solubility enhancement, controlled release, and site-specific delivery. Special consideration is given to emerging multifunctional platforms with biomedical relevance. The regulatory status of CDs is addressed, with reference to FDA- and EMA-approved formulations. Safety profiles and toxicological considerations associated with chemically modified CDs, particularly for parenteral use, are highlighted. This review presents an integrative perspective on the design, characterization, and application of CD-based systems, with a focus on translational potential and current challenges in pharmaceutical development. Full article

Arsenic (As) and cadmium (Cd) in rice grains are major global food safety concerns. Iron (Fe) can help reduce both, but current Fe treatments suffer from poor stability, low leaf absorption, and fast soil immobilization, with unclear underlying mechanisms. To address these issues, an Fe-based metal–organic framework (MIL-88) was modified with sodium alginate (SA) to form MIL-88@SA. Its stability as a foliar inhibitor and its leaf absorption were tested, and its effects on As and Cd accumulation in rice were compared with those of soluble Fe (FeCl₃) and chelating Fe (HA + FeCl₃) in a field study on As–Cd co-contaminated rice paddies. Compared with the control, MIL-88@SA outperformed or matched the other Fe treatments. A single foliar spray during the tillering stage increased the rice yield by 19% and reduced the inorganic As and Cd content in the grains by 22.8% and 67.8%, respectively, while the other Fe treatments required two sprays. Its superior performance was attributed to better leaf affinity and thermal stability. Laser ablation inductively coupled plasma–mass spectrometry (LA–ICP–MS) and confocal laser scanning microscopy (CLSM) analyses revealed that Fe improved photosynthesis and alleviated As–Cd stress in leaves, MIL-88@SA promoted As and Cd redistribution, and Fe–Cd co-accumulation in leaf veins enhanced Cd retention in leaves. Full article

This study identifies the novel effects of soluble factors derived from murine erythroblasts on lymphoid cell phenotypes. These effects were observed following the treatment of splenic mononuclear cells with erythroblast-conditioned media received from both healthy mice and mice subjected to hematopoiesis-activating conditions (hypoxia, blood loss, and hemolytic anemia), suggesting a common mechanism of action. Using flow cytometry, we elucidated that erythroblast-derived soluble products modulate T cell differentiation by promoting Treg development and increasing PD-1 surface expression on B cells. The immunoregulatory potential of erythroblasts is subpopulation-dependent: CD45+ erythroblasts respond to hemolytic stress by upregulating the surface expression of immunosuppressive molecules PDL1 and Galectin-9, while CD45- erythroblasts primarily increase TGFb production. These findings highlight the regulatory role of erythroblasts in modulating immune responses. Full article