Search Results (23)

Parkinson’s disease (PD) is a neurodegenerative disorder marked by the progressive loss of dopaminergic neurons in the nigrostriatal pathway. The dopamine active transporter (DAT), a key protein involved in dopamine reuptake, serves as a selective biomarker for dopaminergic terminals in the striatum. DAT binding has been extensively studied using in vivo imaging techniques such as Single-Photon Emission Computed Tomography (SPECT) and Positron Emission Tomography (PET). To support the design of new radiotracers targeting DAT, we employ Quantitative Structure–Activity Relationship (QSAR) analysis on a structurally diverse dataset composed of 57 compounds with known affinity constants for DAT. The best-performing QSAR model includes four molecular descriptors and demonstrates robust statistical performance: R² = 0.7554, Q²_LOO = 0.6800, and external R² = 0.7090. These values indicate strong predictive capability and model stability. The predicted compounds are evaluated using a docking methodology to check the correct coupling and interactions with the DAT. The proposed approach—combining QSAR modeling and docking—offers a valuable strategy for screening and optimizing potential PET/SPECT radiotracers, ultimately aiding in the neuroimaging and early diagnosis of Parkinson’s disease. Full article

Background: Ethylenediaminetetraacetic acid-dependent pseudo thrombocytopenia (EDTA-PCTP) is defined as a false in vitro decrease in the platelet count performed in the EDTA tube due to the spontaneous formation of platelet aggregates that prevent a correct count in hematological auto analyzers. The frequency of EDTA-PCTP varies depending on the population studied, ranging from 0.01% to 30.0%. In Chile, although the diagnosis of this condition is performed in clinical laboratories, only a few isolated reports have been described. Objectives: To determine the prevalence of EDTA-PCTP in a cohort of patients who attended an outpatient clinical laboratory in southern Chile over a period of almost 4 years. Methods: A retrospective analysis was conducted using the Laboratory Information System from January 2021 to November 2024 to identify patients with suspected and confirmed cases of EDTA-PCTP. Results: The prevalence rate observed was 0.044% (12 out of 27,480). Additionally, we established that platelet count measurement from the citrate tube at 2–5 h post-sampling was comparable to the platelet count from the EDTA/K2 tube at time 0 (p > 0.05) in these patients. Conclusions: We conclude that a relatively low prevalence of EDTA-PTCP was identified in a population of patients attending an outpatient laboratory in Chile, marking the first report of its kind in our country. Future studies may validate our findings to enhance understanding of EDTA-PTCP, thereby preventing incorrect diagnoses and treatments. Full article

Immunotherapy has improved survival in patients with advanced hepatocellular carcinoma (HCC); yet, objective radiological responses occur in only about 20% of cases, suggesting variable benefits. This study aimed to identify serologic markers predictive of response to immune checkpoint inhibitors (ICIs). A cohort of 38 advanced HCC patients receiving immunotherapy was prospectively analyzed. Levels of cell-free DNA (cfDNA), circulating tumor DNA (ctDNA), and cytokines were measured pre-treatment and three months post-treatment initiation. Genomic profiling of ctDNA was also conducted. Baseline levels of cfDNA and ctDNA effectively discriminated HCC patients based on their radiological response to ICIs. Additionally, individuals with pathologic mutations in the CDKN2A gene exhibited significantly reduced survival. Patients with progressive disease (PD) as their best radiological response had significantly fewer copy number variations (CNVs) than those with a radiological response. Furthermore, levels of IL10, PD1, and TGFβ assessed after three months of treatment showed significant variations correlating with survival status. In conclusion, the analysis of cfDNA, ctDNA, and cytokines may improve treatment selection for HCC patients by predicting their expected response to immunotherapies. Full article

Caffeic, syringic, and protocatechuic acids are phenolic acids with important antioxidant activity. In this work we studied how the oxidative stability of rosehip, hemp, and passion fruit oils improves with the addition of these antioxidant acids. We used the BQC-Redox System method to measure the antioxidant activity of oils and phenolic acids, and compared these results with other methods described in the literature. In addition, principal components analysis was used to show the relationship between oxidant activity and fatty acids in the oils studied. The results show, in most cases, the improvement of oxidative stability of oils by addition of phenolic acids, and that oxidative stability is determined by the molecular structure of phenolic acids, solubility of oils, the composition of oils in fatty acids, and the influence of temperature in stabilizing phenolic acids and oils. In addition, we support that the BQC-Redox System (BRS) is a suitable method to measure antioxidant activity. Full article

Background: β-carotene is an essential antioxidant, providing protection against type 2 diabetes mellitus, cardiovascular illnesses, obesity, and metabolic syndrome. This study investigates the impact of β-carotene on biochemical parameters and pancreatic insulin expression in mice exposed to ethanol. Methods: Thirty-six C57BL/6 mice (Mus musculus) were divided into six groups: 1. C (control), 2. LA (3% alcohol dose), 3. MA (7% alcohol dose), 4. B (0.52 mg/kg body weight/day β-carotene), 5. LA+B (3% alcohol dose + 0.52 mg/kg body weight/day β-carotene), and 6. MA+B (7% alcohol dose plus 0.52 mg/kg body weight/day β-carotene). After 28 days, the animals were euthanized for serum and pancreatic tissue collection. Biochemical analysis and pancreatic insulin expression were performed. One-way ANOVA was used. Results: The B, LA+B, and MA+B groups improved insulin levels and decreased HOMA-β versus the C group, with the LA+B and MA+B groups also showing lower ADH and ALDH levels than their nonsupplemented counterparts (p < 0.05). The B, LA+B, and MA+B groups showed a greater β-cell mass area compared to the unsupplemented groups. Additionally, the LA+B and MA+B groups demonstrated significantly increased β-cell area and integrated optical density compared to the LA and MA groups, respectively (p < 0.001). Conclusions: In mice, β-cell loss led to increased glucose release due to decreased insulin levels. β-carotene appeared to mitigate ethanol’s impact on these cells, resulting in reduced insulin degradation when integrated optical density was used. These findings suggest that antioxidant supplementation may be beneficial in treating ethanol-induced type 2 diabetes in animal models. Full article

Leukemia invades the bone marrow progressively and, through unknown mechanisms, outcompetes healthy hematopoiesis. Protein arginine methyltransferases 1 (PRMT1) are found in prokaryotes and eukaryotes cells. They are necessary for a number of biological processes and have been linked to several human diseases, including cancer. Small compounds that target PRMT1 have a significant impact on both functional research and clinical disease treatment. In fact, numerous PRMT1 inhibitors targeting the S-adenosyl-L-methionine binding region have been studied. Through topographical descriptors, quantitative structure-activity relationships (QSAR) were developed in order to identify the most effective PRMT1 inhibitors among 17 compounds. The model built using linear discriminant analysis allows us to accurately classify over 90% of the investigated active substances. Antileukemic activity is predicted using a multilinear regression analysis, and it can account for more than 56% of the variation. Both analyses are validated using an internal “leave some out” test. The developed model could be utilized in future preclinical experiments with novel drugs. Full article

Background: Cell-free DNA (cfDNA) concentrations have been described to be inversely correlated with prognosis in cancer. Mutations in HCC-associated driver genes in cfDNA have been reported, but their relation with patient’s outcome has not been described. Our aim was to elucidate whether mutations found in cfDNA could be representative from those present in HCC tissue, providing the rationale to use the cfDNA to monitor HCC. Methods: Tumoral tissue, paired nontumor adjacent tissue and blood samples were collected from 30 HCC patients undergoing curative therapies. Deep sequencing targeting HCC driver genes was performed. Results: Patients with more than 2 ng/µL of cfDNA at diagnosis had higher mortality (mean OS 24.6 vs. 31.87 months, p = 0.01) (AUC = 0.782). Subjects who died during follow-up, had a significantly higher number of mutated genes (p = 0.015) and number of mutations (p = 0.015) on cfDNA. Number of mutated genes (p = 0.001), detected mutations (p = 0.001) in cfDNA and ratio (number of mutations/cfDNA) (p = 0.003) were significantly associated with recurrence. However, patients with a ratio (number of mutations/cfDNA) above 6 (long-rank p = 0.0003) presented a higher risk of recurrence than those with a ratio under 6. Detection of more than four mutations in cfDNA correlated with higher risk of death (long-rank p = 0.042). Conclusions: In summary, cfDNA and detection of prevalent HCC mutations could have prognostic implications in early-stage HCC patients Full article

Understanding fishway attraction is one of the main open challenges in fishways research, and unraveling the mechanisms and relationships that trigger it is crucial to improve the performance of fishways. Furthermore, attraction is usually understood in terms of upstream migration; however, taking into account the possible bidirectional use of fishways, it is equally important to study this phenomenon during downstream migration, although this is usually considered negligible. Therefore, this study aims to advance our understanding of fishway attraction efficiency by considering both upstream and downstream movements in a key small hydropower plant scheme in the Iberian Peninsula. To achieve this, one of the most common Iberian fish species, the Iberian barbel (Luciobarbus bocagei, Steindachner), was monitored via telemetry in a stepped fishway. The studied fishway, considering the specialized literature, would be classified as poor in attraction, i.e., difficult to find due to its low competing discharge and the long distance between the main river flow and both fishway entrances. Fish were PIT tagged and released in different upstream and downstream locations and on different dates. The results showed that a significant proportion of the tagged barbels was able to successfully locate the fishway from both sides, in spite of the mentioned localization drawbacks, with inter-annual variability and with repeated events throughout the years. This suggests that even a fishway with a theoretical poor attraction can still be localized by fish, allowing their use as a two-way migration route, at least with species and HPP schemes such as those already studied. Full article

Based on a set of six vector properties, the partial correlation diagram is calculated for a set of 28 S-alkylcysteine diazomethyl- and chloromethyl-ketone derivatives. Those with the greatest antileukemic activity in the same class correspond to high partial correlations. A periodic classification is performed based on information entropy. The first four characteristics denote the group, and the last two indicate the period. Compounds in the same period and, especially, group present similar properties. The most active substances are situated at the bottom right. Nine classes are distinguished. The principal component analysis of the homologous compounds shows five subclasses included in the periodic classification. Linear fits of both antileukemic activities and stability are good. They are in agreement with the principal component analysis. The variables that appear in the models are those that show positive loading in the principal component analysis. The most important properties to explain the antileukemic activities (50% inhibitory concentration Molt-3 T-lineage acute lymphoblastic leukemia minus the logarithm of 50% inhibitory concentration Nalm-6 B-lineage acute lymphoblastic leukemia and stability k) are ACD logD, surface tension and number of violations of Lipinski’s rule of five. After leave-m-out cross-validation, the most predictive model for cysteine diazomethyl- and chloromethyl-ketone derivatives is provided. Full article

Seventeen isoflavonoids from isoflavone, isoflavanone and isoflavan classes are selected from Dalbergia parviflora. The ChEMBL database is representative from these molecules, most of which result highly drug-like. Binary rules appear risky for the selection of compounds with high antioxidant capacity in complementary xanthine/xanthine oxidase, ORAC, and DPPH model assays. Isoflavonoid structure-activity analysis shows the most important properties (log P, log D, pK_a, QED, PSA, NH + OH ≈ HBD, N + O ≈ HBA). Some descriptors (PSA, HBD) are detected as more important than others (size measure Mw, HBA). Linear and nonlinear models of antioxidant potency are obtained. Weak nonlinear relationships appear between log P, etc. and antioxidant activity. The different capacity trends for the three complementary assays are explained. Isoflavonoids potency depends on the chemical form that determines their solubility. Results from isoflavonoids analysis will be useful for activity prediction of new sets of flavones and to design drugs with antioxidant capacity, which will prove beneficial for health with implications for antiageing therapy. Full article

Pesticide residues in wine were analyzed by liquid chromatography–tandem mass spectrometry. Retentions are modelled by structure–property relationships. Bioplastic evolution is an evolutionary perspective conjugating effect of acquired characters and evolutionary indeterminacy–morphological determination–natural selection principles; its application to design co-ordination index barely improves correlations. Fractal dimensions and partition coefficient differentiate pesticides. Classification algorithms are based on information entropy and its production. Pesticides allow a structural classification by nonplanarity, and number of O, S, N and Cl atoms and cycles; different behaviours depend on number of cycles. The novelty of the approach is that the structural parameters are related to retentions. Classification algorithms are based on information entropy. When applying procedures to moderate-sized sets, excessive results appear compatible with data suffering a combinatorial explosion. However, equipartition conjecture selects criterion resulting from classification between hierarchical trees. Information entropy permits classifying compounds agreeing with principal component analyses. Periodic classification shows that pesticides in the same group present similar properties; those also in equal period, maximum resemblance. The advantage of the classification is to predict the retentions for molecules not included in the categorization. Classification extends to phenyl/sulphonylureas and the application will be to predict their retentions. Full article

The Silberstein model of the molecular polarizability of diatomic molecules, generalized by Applequist et al. for polyatomic molecules, is analyzed. The atoms are regarded as isotropically polarizable points located at their nuclei, interacting via the fields of their induced dipoles. The use of additive values for atom polarizabilities gives poor results, in some cases leading to artificial predictions of absorption bands. The molecular polarizability of methane and its derivative are computed. The agreement with experimental mean molecular polarizabilities is within 1–5%. A hypothesis is indispensable for a suitable representation of polarizability derivative. Full article

Algorithms for classification are proposed based on criteria (information entropyand its production). The feasibility of replacing a given anaesthetic by similar ones in thecomposition of a complex drug is studied. Some local anaesthetics currently in use areclassified using characteristic chemical properties of different portions of their molecules.Many classification algorithms are based on information entropy. When applying theseprocedures to sets of moderate size, an excessive number of results appear compatible withdata, and this number suffers a combinatorial explosion. However, after the equipartitionconjecture, one has a selection criterion between different variants resulting fromclassification between hierarchical trees. According to this conjecture, for a given charge orduty, the best configuration of a flowsheet is the one in which the entropy production is mostuniformly distributed. Information entropy and principal component analyses agree. Theperiodic law of anaesthetics has not the rank of the laws of physics: (1) the properties ofanaesthetics are not repeated; (2) the order relationships are repeated with exceptions. Theproposed statement is: The relationships that any anaesthetic p has with its neighbour p 1are approximately repeated for each period. Full article

Valence topological charge-transfer (CT) indices are applied to the calculationof dipole moments. The algebraic and vector semisum CT indices are defined. Thecombination of CT indices allows the estimation of the dipole moments. The model isgeneralized for molecules with heteroatoms. The ability of the indices for the descriptionof the molecular charge distribution is established by comparing them with the dipolemoments of homologous series of percutaneous enhancers (phenyl alcohols and4-alkylanilines). Linear and quadratic correlation models are obtained. CT indicesimprove the multivariable quadratic regression equations for the dipole moment. Thevariance decreases 97% (4-alkylanilines). No superposition of the corresponding G_k–J_kand G_k^V–J_k^V pairs is observed in the fits, which diminishes the risk of co-linearity. Theinclusion of the heteroatom in the π-electron system is beneficial for the description ofthe dipole moment, owing to either the role of the additional p orbitals provided by theheteroatom or the role of steric factors in the π-electron conjugation. Inclusion of aconjugated double bond in the alkyl chain lends to more rigid structures with dipolemoment variations lower than1%. Full article

This report describes a new set of macromolecular descriptors of relevance toprotein QSAR/QSPR studies, protein’s quadratic indices. These descriptors are calculatedfrom the macromolecular pseudograph’s α-carbon atom adjacency matrix. A study of theprotein stability effects for a complete set of alanine substitutions in Arc repressorillustrates this approach. Quantitative Structure-Stability Relationship (QSSR) modelsallow discriminating between near wild-type stability and reduced-stability A-mutants. Alinear discriminant function gives rise to excellent discrimination between 85.4% (35/41)and 91.67% (11/12) of near wild-type stability/reduced stability mutants in training andtest series, respectively. The model’s overall predictability oscillates from 80.49 until82.93, when n varies from 2 to 10 in leave-n-out cross validation procedures. This valuestabilizes around 80.49% when n was Full article