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Relevance of pre-analytical factors in multiomics: Toward a standardized blood processing protocol
No full textTo implement multiomic studies successfully, there is a need to overcome challenges in steps ranging from study design to data integration. As blood is the preferred matrix for sampling in such studies, we review how pre-analytical factors affect genomics, transcriptomics, proteomics, and metabolomics and propose a harmonized blood processing protocol. Plasma is preferred, as clotting of serum may cause contamination from lysed cells. Transcriptomics is highly sensitive to platelet contamination, making platelet-poor plasma ideal. Processing delays and room-temperature storage compromise the stability of several analytes classes. To ensure comparability, the Standard PREanalytical Code (SPREC) should document all phases of sample handling. We recommend collecting blood in K2EDTA tubes and separating plasma via two centrifugations (1600×g and 16,000×g, 10 min at 4 °C). Samples should be checked for hemolysis, icterus, and lipemia and then stored at −80 °C [SPREC: PL2.PED.A1.C.J.A.D]. Following this standardized protocol or documenting deviations from it can improve multiomic reproducibility
Phytochemical analysis, biological activities and molecular docking studies of black and white goji fruits of Lycium ruthenicum Murray
No full textThis study analyzes the phenolic and phenylamide composition of black and white goji berries, identifying 31 phenolics, 28 phenylamides, and 3 organic acids. Black berries contained about 10-fold higher phenolics, particularly hydroxybenzoic acid derivatives and anthocyanins, while white berries were dominated by phenolic acids and glycosylated spermidine/spermine derivatives. Glycosides of myricetin and laricitrin in black berries and caffeoyl putrescine monohexosides in both types, were identified. Phenylamide profiles differed, with N-caffeoyl-N′-dihydrocaffeoyl spermidine as the most abundant and bioactive. Both extracts showed antioxidant and enzyme-inhibitory effects. Black goji displayed stronger tyrosinase inhibition consistent with its high phenolic content and synergism among phenolics and phenylamides. Molecular docking revealed strong interactions with AChE and tyrosinase, especially for N-caffeoyl-N′-dihydrocaffeoyl spermidine, which showed higher affinity for tyrosinase than standard inhibitors. The presence of sugar moieties in some compounds reduced binding stability. These results highlight goji berries as promising sources of bioactives, for functional foods and nutraceuticals
Beyond colonization: Candida albicans exhibits substantial pathogenic potential in cystic fibrosis environments
No full textCystic fibrosis (CF) sputum represents a highly permissive niche for microbial colonization, yet the contribution of Candida albicans to disease progression remains insufficiently investigated despite its frequent detection in CF airways. We hypothesized that the heterogeneous nature of CF lung, reflected through the emergence of oxygen-depleted niches during disease progression, modulates C. albicans pathogenicity and antifungal susceptibility. Using complementary in vitro and in vivo approaches, we show that clinical CF isolates of C. albicans are virulent in CF-mimicking environments. Synthetic CF medium (SCFM2) supported robust filamentation, with oxygen-nutrient interplay critically shaping fungal growth and drug response. In a novel CF infection model using zebrafish morphants, we observed heightened susceptibility to C. albicans compared to wild-type embryos. Reporter strains showed elevated ECE1 expression, indicating increased candidalysin production and virulence in vivo. Our study provides compelling evidence that CF isolates of C. albicans have pathogenic potential, warranting consideration in future therapeutic strategies
Bentonite–Chitosan–Surfactant Composite with Antimicrobial, Antioxidant, and Mycotoxin Adsorption Properties
No full textThis study aimed to design a new composite with promising antimicrobial and antioxidant properties by a simple modification process of natural bentonite (B) with polysaccharide chitosan isolated from edible mushrooms Agaricus bisporus—ChM (sample B–ChM) and subsequently with a cationic surfactant—hexadecyltrimethylammonium bromide—HB (sample B–ChM–HB) for effective removal of mycotoxin zearalenone (ZEN). Characterization confirmed the presence of ChM in B–ChM and both ChM and HB in B–ChM–HB. Compared to non- or slightly inhibitory activity of B and B–ChM, B–ChM–HB showed fungicidal activity against yeast Candida albicans and mycotoxigenic mold Aspergillus flavus, with a reduction of 6.00 log10 (CFU/mL) and 5.32 log10 (CFU/mL), respectively. B–ChM–HB showed a very high neutralization ability on •DPPH (89.03%–95.99%) in the concentration range of 0.625–5.0 mg/mL, the highest ferrous ion chelating ability (80.25%) at a concentration of 0.625 mg/mL, and did not induce lipid peroxidation in the linoleic acid model system. While B and B–ChM exhibited low adsorption of ZEN, its adsorption by B–ChM–HB was significantly higher. The equilibrium results of B–ChM–HB for ZEN were in accordance with the linear isotherm model at pH 3 and 7, pointing out that hydrophobic interactions (partitioning process) were relevant for toxin adsorption by the composite. Similar maximum ZEN adsorbed amounts under the applied experimental conditions (14.4 mg/g) at both pH values suggested that its adsorption was independent of the pH. This study reported for the first time that a novel composite of B with ChM and HB showed promising antimicrobial and antioxidant properties and was an efficient adsorbent for mycotoxin ZEN
Valorization of Lemon, Apple, and Tangerine Peels and Onion Skins–Artificial Neural Networks Approach
No full textThis study focuses on the optimization of modern extraction techniques for selected by-product materials, including apple, lemon, and tangerine peels, and onion skins, using artificial neural network (ANN) models. The extraction methods included ultrasound-assisted extraction (UAE) and microwave-assisted extraction (MAE) with water as the extractant, as well as maceration (MAC) with natural deep eutectic solvents (NADES). Key parameters, such as total phenolic content (TPC), total flavonoid content (TFC), and antioxidant activities, including reducing power (EC50) and free radical scavenging capacity (IC50), were evaluated to compare the efficiency of each method. Among the techniques, UAE outperformed both MAE and MAC in extracting bioactive compounds, especially from onion skins and tangerine peels, as reflected in the highest TPC, TFC, and antioxidant activity. UAE of onion skins showed the best performance, yielding the highest TPC (5.735 ± 0.558 mg CAE/g) and TFC (1.973 ± 0.112 mg RE/g), along with the strongest antioxidant activity (EC50 = 0.549 ± 0.076 mg/mL; IC50 = 0.108 ± 0.049 mg/mL). Tangerine peel extracts obtained by UAE also exhibited high phenolic content (TPC up to 5.399 ± 0.325 mg CAE/g) and strong radical scavenging activity (IC50 0.118 ± 0.099 mg/mL). ANN models using multilayer perceptron architectures with high coefficients of determination (r2 > 0.96) were developed to predict and optimize the extraction results. Sensitivity and error analyses confirmed the robustness of the models and emphasized the influence of the extraction technique and by-product type on the antioxidant parameters. Principal component and cluster analyses showed clear grouping patterns by extraction method, with UAE and MAE showing similar performance profiles. Overall, these results underline the potential of UAE- and ANN-based modeling for the optimal utilization of agricultural by-products
Combination of oximes as experimental therapeutic approach to organophosphates poisonings: a critical review
No full textIn this paper we have made efforts to compile and critically review the existing scientific evidence on the efficacy of combined oxime treatment as potential alternative or interim solution in organophosphate poisonings in the absence of universal single oxime. Literature review identified binary combinations of oximes that included apart from standard four (pralidoxime, trimedoxime, obidoxime and asoxime) also promising experimental oximes (K203 and phenoxyalkyl pyridinium oximes). Their effectiveness was confronted to nerve agents, and some organophosphate insecticides. Although few in vitro studies were found, the most studies were done in vivo on intoxicated mice, rats or guinea pigs. Some beneficial effects of combined oxime treatment were found for particular organophosphate poisonings. However, the majority of studies are incomparable due to interspecies differences or differences in the experimental setups. The need for appropriate oxime dosing was found via extrapolation of animal doses to human relevant doses. Thus, the further and rational approach is need to confirm or disprove advantages of the combined oxime treatment for organophosphate poisoning
Nutritional and Antioxidant Comparison of Oil Press Cakes and Wheat Flours
No full textPlants are sources of compounds with important effects on health, but plant-based food industry generates substantial waste amounts, especially in oil production. This study aimed to characterize flours derived from oilseed by-products, pumpkin, sunflower, and apricot seed residues, and compare them with conventional grain flours (white and whole wheat). Nutritional composition was analyzed with emphasis on amino acid profiles performed by ion chromatography. Mineral profiles were determined by ICP-MS. Total phenolics and antioxidant activity were assessed using in vitro colorimetric microassays. Oil press cake flours showed significantly higher levels of protein and fiber compared to wheat flours (p < 0.05), while the latter contained more carbohydrates. Among the examined flours, pumpkin and apricot seed flours stood out with the highest potassium, while sunflower seed flour led in calcium content. Despite higher polyphenol content in wheat flours, apricot seed flour exhibited the greatest antioxidant activity, likely due to its diverse profile of hydrophilic and lipophilic bioactive compounds. These findings highlight oil press cakes as nutritionally valuable ingredients for protein-enriched and other innovative food products, aligning with circular economy principles and promoting resource efficiency in the agri-food sector
Carcinogenic Health Risk Assessment of Benzo[a]Pyrene Bound to PM 10 in Adult and Children Population Through Ambient Air in Belgrade City, Serbia
No full textParticulate matter (PM) contains various components, among which heavy metals and polycyclic aromatic hydrocarbons (PAHs) are considered the main toxic component. Serbia, a middle-income country in Southeast Europe, faces PM pollution in several towns. This study aimed to assess the carcinogenic health risk of exposure to B[a]P, a representative PAH, in Belgrade for adults and children during heating and non-heating seasons, using deterministic and probabilistic approaches for the 2018–2022 period. Average PM10 levels ranged between 32.6 and 45.3 μg/m3, and B[a]P levels between 1.4 and 3.7 ng/m3. The PM10 annual limit (40 μg/m3) was exceeded at five of fourteen stations, while the B[a]P annual limit (1 ng/m3) was exceeded at all considered monitoring stations. Risk assessment using both approaches resulted in Total Cancer Risk (TCR) values below the USEPA safe limit (1.0E-04) for both populations and seasons. Deterministic TCR values exceeded the 95th percentile (P95) of the probabilistic risk distribution, which represents the reasonable maximum exposure level according to USEPA. The highest TCR was obtained for adults during the heating season using both deterministic (5.63E-05) and probabilistic approach (1.60E-05, P95). Our results indicate that the probabilistic approach provides a more accurate representation of overall risk, leading to better risk management decisions, while the deterministic approach is more conservative due to reliance on average parameter values. Although the carcinogenic risk of B[a]P in Belgrade was acceptable, other PM compounds and exposure pathways should be considered simultaneously to achieve a more accurate health risk assessment
Current Computational Approaches for the Discovery of Novel Anticancer Agents Targeting VEGFR and SIRT Signaling Pathways
No full textNumerous scientific studies highlight the crucial role of common genetic and epigenetic
factors in the development and progression of cancer. To deepen our understanding of how
different VEGFR and epigenetic pathways interact in carcinogenesis, the current review
examines novel therapeutic agents that target various molecular mechanisms involved
in this complex disease. Growing evidence from scientific studies suggests that VEGFR
and epigenetic signaling pathways contribute to complex pathophysiological changes in
cancer. Therefore, simultaneously targeting VEGFR and epigenetic factors, such as sirtuins,
by developing dual inhibitors could provide more individualized therapeutic approaches
with safer and more effective outcomes. In this context, Computer-Aided Drug Design
(CADD) offers a comprehensive suite of bioinformatic, chemoinformatic, and chemometric
approaches to design novel chemotypes of epigenetic dual-target inhibitors. This facilitates
the efficient discovery of new drug candidates, enabling innovative treatments for these
multifactorial diseases. The review also explores the detailed anticancer mechanisms
by which VEGFR, SIRT, and dual-target inhibitors modify metastatic and tumorigenic
properties, affect the tumor microenvironment, and regulate the immune response
Innovative Diabetes Therapies and Impact on Peripheral and Autonomic Diabetic Neuropathies: A State‑of‑the‑Art Review
No full textAs a leading complication of diabetes mellitus, diabetic neuropathy (DN) represents a major public health challenge due to its high prevalence and impact on patients’ quality of life. The most common form, diabetic peripheral neuropathy (DPN), is characterized by progressive sensory loss, neuropathic pain, and autonomic dysfunction, all of which can significantly increase the risk of serious complications, such as foot ulcers and amputations. Traditionally, therapeutic strategies for DN have been largely limited to symptomatic management. However, recent advancements in diabetes therapy have opened promising avenues for disease-modifying interventions. In particular, incretin-based therapies and sodium-glucose co-transporter 2 (SGLT2) inhibitors have attracted increasing interest not only for their glucose-lowering effects, but also for their broader metabolic, renal, and cardiovascular benefits. In this narrative review, we synthesize emerging evidence on the potential role of these innovative therapies in the management of DN. Preclinical models, clinical trials and real-world observational studies strongly support the hypothesis that glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and SGLT2 inhibitors may confer neuroprotective benefits. Beyond these established classes, novel agents such as dual and triple receptor agonists are currently being investigated. Although clinical data on their effects in DN are still limited, the simultaneous activation of multiple metabolic pathways suggests the potential for synergistic neuroprotective effects through enhanced regulation of glucose and lipid metabolism, attenuation of systemic inflammation and oxidative stress, improvement of mitochondrial function and reduction of neuronal damage. Although innovative diabetes therapies are still in early stages of development, they reflect a rapidly evolving landscape in the management of DN in the future