Reactivity of zinc fingers in oxidizing environments: insight from molecular models through activation strain analysis.

The reactivity of Zn2+ tetrahedral complexes with H2O2 was investigated in silico, as first step for the process of their disruption. The substrates were chosen to represent the cores of three different zinc finger protein motifs, i.e., a Zn2+ ion coordinated to four cysteines (CCCC), to three cysteines and one histidine (CCCH), and to two cysteines and two histidines (CCHH). The cysteine and histidine ligands were further simplified to methyl thiolate and imidazole, respectively. H2O2 was chosen as oxidizing agent because of its biological role as metabolic product and species involved in signaling processes. The mechanism of oxidation of a coordinated cysteinate to sulfenate-κS and the trends for the different substrates were rationalized through activation strain analysis and energy decomposition analysis in the framework of scalar relativistic DFT calculations at ZORA-M06/TZ2P ae // ZORA-BLYP-D3(BJ)/TZ2P. CCCC is oxidized most easily, an outcome explained considering both electrostatic and orbital interactions. The isomerization to sulfenate-κO was attempted to assess whether this step may affect the ligand dissociation; but it was found to introduce a kinetic barrier without improving the energetics of the dissociation. Lastly, ligand exchange with free thiolates and selenolates was investigated as trigger for ligand dissociation, possibly leading to metal ejection.

Quality Studies on Cynometra iripa Leaf and Bark as Herbal Medicines.

Cynometra iripa Kostel. is a Fabaceae species of mangrove used in traditional Ayurvedic medicine for treating inflammatory conditions. The present study aims to establish monographic botanical and chemical quality criteria for C. iripa leaf and bark as herbal substances and to evaluate their in vitro antioxidant potential. Macroscopic and microscopic qualitative and quantitative analyses, chemical LC-UV/DAD-ESI/MS profiling, and the quantification of key chemical classes were performed. Antioxidant activity was evaluated by DPPH and FRAP assays. Macroscopically, the leaf is asymmetrical with an emarginated apex and cuneate base. Microscopically, it shows features such as two-layered adaxial palisade parenchyma, vascular bundles surrounded by 3-6 layers of sclerenchyma, prismatic calcium oxalate crystals (5.89 ± 1.32 µm) along the fibers, paracytic stomata only on the abaxial epidermis (stomatal index-20.15), and non-glandular trichomes only on petiolules. The microscopic features of the bark include a broad cortex with large lignified sclereids, prismatic calcium oxalate crystals (8.24 ± 1.57 µm), and secondary phloem with distinct 2-5 seriated medullary rays without crystals. Chemical profile analysis revealed that phenolic derivatives, mainly condensed tannins and flavonoids, are the main classes identified. A total of 22 marker compounds were tentatively identified in both plant parts. The major compounds identified in the leaf were quercetin-3-O-glucoside and taxifolin pentoside and in the bark were B-type dimeric proanthocyanidins and taxifolin 3-O-rhamnoside. The total phenolics content was higher in the leaf (1521 ± 4.71 mg GAE/g dry weight), while the total flavonoids and condensed tannins content were higher in the bark (82 ± 0.58 mg CE/g and 1021 ± 5.51 mg CCE/g dry weight, respectively). A total of 70% of the hydroethanolic extracts of leaf and bark showed higher antioxidant activity than the ascorbic acid and concentration-dependent scavenging activity in the DPPH assay (IC50 23.95 ± 0.93 and 23.63 ± 1.37 µg/mL, respectively). A positive and statistically significant (p < 0.05) correlation between the phenol content and antioxidant activity was found. The results obtained will provide important clues for the quality control criteria of C. iripa leaf and bark, as well as for the knowledge of their pharmacological potential as possible anti-inflammatory agents with antioxidant activity.

Influence of baking time and formulation of part-baked wheat sourdough bread on the physical characteristics, sensory quality, glycaemic index and appetite sensations.

Raw materials and process parameters in bread production can modulate the glycemic index, which on itself has been linked with provision of better hunger satisfaction and maintaining better satiation. The objective of this research was to investigate if using unrefined wheat flour or the addition of intact cereals in formulation or alternating the baking time would have an effect on physical characteristics, sensory quality, glycaemic index and appetite sensations in wheat sourdough bread. In the study, three types of commercial part-baked frozen sourdough bread, baked to the final baking for two different times (long and short baking time) were used. A randomized controlled crossover trial was performed with 10 healthy adults who consumed sufficient quantity of bread to ingest 50 g available carbohydrates. Participants self-reported appetite sensations (desire to eat, hunger, fullness, satisfaction, appetite) on a 10 cm visual analog scale (VAS) scale in a course of 180 min. In addition, bread products were subjected to overall acceptability and different sensory attributes were examined on JAR "just about right" scale. Different bread formulations (refined flour, unrefined wheat flour, cereal flour or intact cereals) and different length of baking time significantly influenced (p < 0.005) physical, textural and sensory features of products. The alternation of aforementioned parameters decreased the glycemic index, but not significantly (p > 0.005). No correlation was found between lower GI, satiety and satiation. Liking score and incremental area under the curve (iAUC) of satiety and satiation were calculated as highest in sourdough bread with added cereals.

Impact of resistant starch: Absorption of dietary minerals, glycemic index and oxidative stress in healthy rats.

BACKGROUND & AIMS: Resistant starch (RS) is a prebiotic fiber that has been scientifically shown to control the development of obesity. Prebiotic role of RS has also seen to be very important as it helps gut bacteria to regulate fermentation and fatty acid production. This study aimed to check the different levels of RS on glycemic index, oxidative stress and mineral absorption rate in healthy rat models. To evaluate these objectives, the trial was conducted for 40 days of follow up; 10 days were the adjustment period and the collection period over 30 days. METHODS: Thirty-six healthy female Wistar rats were divided into 4 groups of (9 animals each) NC (Normal Control: without resistant starch), RS0.20 (resistant starch: 0.20 g/kg body weight), RS0.30 (resistant starch: 0.30 g/kg body weight), RS0.40 (resistant starch: 0.40 g/kg body weight). All the diets were isocaloric and isonitroginous. RESULTS: The impact of different levels of RS on the dry-matter intake (DMI) presented statistically significant results (p ≤ 0.05): DMI was reduced in RS (0.02) fed rats as compared to NC rats in first 3 weeks; and after 4th and 5th weeks, there was a DMI reduction of 28% in RS (0.04) fed rats. Moreover, there was no significant increase in the nutrient intake in all RS diets. The dry-matter (DM) digestibility was statistically significantly (P ≤ 0·05), which increased in all rats fed with different level of RS. The weight loss showed statistically significant results: RS (0.04) exhibited 19 g reduction in weight as compared with NC rats. Significant increase was observed in total oxidant status (TOS), in all the RS fed rats when compared with NC rats. The levels of Mg, Ca, Fe and Zn were shown to be decrease in feces analysis, which proves their better absorbance in gut. Statistically significant increase was observed in antioxidant capacity, whereas significant decrease was observed in the total weight of the animals, showing the role of RS in controlling obesity. CONCLUSIONS: Overall, significant results were found in all dosage level of RS but long term administration of the higher dosage level (RS0.40) may need to be studied for enhanced results. RS can help improve insulin sensitivity in overweight adults.

Oncology Education in Angola: Current Status and Recommendations for Improvement.

Angola, a country grappling with prevalent tropical diseases such as malaria, is witnessing an alarming rise in cancer-related deaths. Despite the escalating significance of cancer globally and in Angola, the nation's medical schools lack compulsory oncology disciplines in their curricula. This absence compromises the comprehensive training of medical students, preventing the development of integrated perspectives and skills crucial for addressing the growing cancer burden. This article, authored by the Angolan Oncology Research Group (AORG), proposes an oncology program for undergraduate medical students in Angola, aiming to bridge the educational gap. The program outlines discipline objectives, topics to be covered, class formats, and workload considerations.

Inhibition of the morphological transition of Candida spp. by riparins I-IV.

Candida spp. is an opportunistic pathogen capable of causing superficial to invasive infections. Morphological transition is one of the main virulence factors of this genus and, therefore, is an important variable to be considered in pharmacological interventions. Riparins I, II, III, and IV are alkamide-type alkaloids extracted from the unripe fruit of Aniba riparia, whose remarkable pharmacological properties were previously demonstrated. This work aimed to evaluate in silico and in vitro the inhibitory effects of Riparins on the morphological transition of Candida albicans, Candida tropicalis, and Candida krusei. Molecular docking was applied to analyze the inhibitory effects of riparins against proteins such as N-acetylglucosamine, CYP-51, and protein kinase A (PKA) using the Ramachandran plot. The ligands were prepared by MarvinSketch and Spartan software version 14.0, and MolDock Score and Rerank Score were used to analyze the affinity of the compounds. In vitro analyses were performed by culturing the strains in humid chambers in the presence of riparins or fluconazole (FCZ). The morphology was observed through optical microscopy, and the size of the hyphae was determined using the ToupView software. In silico analysis demonstrated that all riparins are likely to interact with the molecular targets: GlcNAc (>50%), PKA (>60%), and CYP-51 (>70%). Accordingly, in vitro analysis showed that these compounds significantly inhibited the morphological transition of all Candida strains. In conclusion, this study demonstrated that riparins inhibit Candida morphological transition and, therefore, can be used to overcome the pathogenicity of this genus.

Designing a Multiepitope Vaccine against the Foodborne Pathogenic Bacteria Listeria monocytogenes Using Subtractive Immunoinformatics Approaches.

BACKGROUND: Listeria monocytogenes, a Gram-positive bacterium, is a prominent foodborne pathogen that causes listeriosis and poses substantial health hazards worldwide. The continuing risk of listeriosis outbreaks underlies the importance of designing an effective prevention strategy and developing a robust immune response by reverse vaccinology approaches. This study aimed to provide a critical approach for developing a potent multiepitope vaccine against this foodborne disease. METHODS: A chimeric peptide construct containing 5 B-cell epitopes, 16 major histocompatibility complex I (MHC-I) epitopes, and 18 MHC-II epitopes were used to create a subunit vaccination against L. monocytogenes. The vaccine safety was evaluated by several online methods, and molecular docking was performed using ClusPro to determine the binding affinity. Immune simulation was performed using the C-ImmSimm server to demonstrate the immune response. RESULTS: The results validated the antigenicity, non-allergenicity, and nontoxicity of the chimeric peptide construct, confirming its suitability as a subunit vaccine. Molecular docking showed a good score of 1276.5 and molecular dynamics simulations confirmed the construct's efficacy, demonstrating its promise as a good candidate for listeriosis prophylaxis. The population coverage was as high as 91.04% with a good immune response, indicating good antigen presentation with dendritic cells and production of memory cells. CONCLUSIONS: The findings of this study highlight the potential of the designed chimeric peptide construct as an effective subunit vaccine against Listeria, paving the way for future advances in preventive methods and vaccine design.

Valorization of Dairy and Fruit/Berry Industry By-Products to Sustainable Marinades for Broilers' Wooden Breast Meat Quality Improvement.

The study aims to improve the quality of wooden breast meat (WBM) via the use of newly developed marinades based on selected strains of lactic acid bacteria (LAB) in combination with the by-products of the dairy and fruit/berry industries. Six distinct marinades were produced based on milk permeate (MP) fermented with Lacticaseibacillus casei (Lc) and Liquorilactobacillus uvarum (Lu) with the addition of apple (ApBp) and blackcurrant (BcBp) processing by-products. The microbiological and acidity parameters of the fermented marinades were evaluated. The effects of marinades on the microbiological, technical, and physicochemical properties of meat were assessed following 24 and 48 h of WBM treatment. It was established that LAB viable counts in marinades were higher than 7.00 log10 colony-forming units (CFU)/mL and, after 48 h of marination, enterobacteria and molds/yeasts in WBM were absent. Marinated (24 and 48 h) WBM showed lower dry-matter and protein content, as well as water holding capacity, and exhibited higher drip loss (by 8.76%) and cooking loss (by 12.3%) in comparison with controls. After WBM treatment, biogenic amines decreased; besides, the absence of spermidine and phenylethylamine was observed in meat marinated for 48 h with a marinade prepared with Lu. Overall, this study highlights the potential advantages of the developed sustainable marinades in enhancing the safety and quality attributes of WBM.

Retinal toxicity of heavy metals and its involvement in retinal pathology.

The objective of the present review is to discuss epidemiological evidence demonstrating the association between toxic metal (Cd, Pb, Hg, As, Sn, Ti, Tl) exposure and retinal pathology, along with the potential underlying molecular mechanisms. Epidemiological studies demonstrate that Cd, and to a lesser extent Pb exposure, are associated with age-related macular degeneration (AMD), while the existing evidence on the levels of these metals in patients with diabetic retinopathy is scarce. Epidemiological data on the association between other toxic metals and metalloids including mercury (Hg) and arsenic (As), are limited. Clinical reports and laboratory in vivo studies have shown structural alterations in different layers of retina following metal exposure. Examination of retina samples demonstrate that toxic metals can accumulate in the retina, and the rate of accumulation appears to increase with age. Experimental studies in vivo and in vitro studies in APRE-19 and D407 cells demonstrate that toxic metal exposure may cause retinal damage through oxidative stress, apoptosis, DNA damage, mitochondrial dysfunction, endoplasmic reticulum stress, impaired retinogenesis, and retinal inflammation. However, further epidemiological as well as laboratory studies are required for understanding the underlying molecular mechanisms and identifying of the potential therapeutic targets and estimation of the dose-response effects.

Unveiling the promising anticancer activity of palladium(II)-aryl complexes bearing diphosphine ligands: a structure-activity relationship analysis.

In continuation of our previous works on the cytotoxic properties of organopalladium compounds, in this contribution we describe the first systematic study of the anticancer activity of Pd(II)-aryl complexes. To this end, we have prepared and thoroughly characterized a wide range of palladium derivatives bearing different diphosphine, aryl and halide ligands, developing, when necessary, specific synthetic protocols. Most of the synthesized compounds showed remarkable cytotoxicity towards ovarian and breast cancer cell lines, with IC50 values often comparable to or lower than that of cisplatin. The most promising complexes ([PdI(Ph)(dppe)] and [PdI(p-CH3-Ph)(dppe)]), characterized by a diphosphine ligand with a low bite angle, exhibited, in addition to excellent cytotoxicity towards cancer cells, low activity on normal cells (MRC5 human lung fibroblasts). Specific immunofluorescence tests (cytochrome c and H2AX assays), performed to clarify the possible mechanism of action of this class of organopalladium derivatives, seemed to indicate DNA as the primary cellular target, whereas caspase 3/7 assays proved that the complex [PdI(Ph)(dppe)] was able to promote intrinsic apoptotic cell death. A detailed molecular docking analysis confirmed the importance of a diphosphine ligand with a reduced bite angle to ensure a strong DNA-complex interaction. Finally, one of the most promising complexes was tested towards patient-derived organoids, showing promising ex vivo cytotoxicity.

Changes in Chemical Composition of Lentils, Including Gamma-Aminobutyric Acid and Volatile Compound Formation during Submerged and Solid-State Fermentation with Pediococcus acidilactici.

The aim of this study was to evaluate and compare the characteristics of non-treated and fermented [via submerged (SMF) and solid-state (SSF) fermentation using Pediococcus acidilactici] lentils (Lens culinaris) grown either in pure stands (L) or relay intercropped with winter rye (LR). It was observed that the lentils were suitable substrate for lacto-fermentation. Most of the free amino acid concentrations increased in lentils after both fermentations. The highest concentration of γ-aminobutyric acid was found in SSF LR samples. However, fermentation led to higher biogenic amines (BA) content in lentils. The most abundant fatty acid in lentils was C18:2. SSF lentils showed more complex volatile compound (VC) profiles (with between nine and seventeen new VCs formed), whereas, in SMF samples, between two and five newly VCs were formed. When comparing lentil grown types, L contained significantly higher concentrations of Na, K, Ca, P, Mn, and Se, while LR contained significantly higher concentrations of Fe and Ni. To sum up, fermentation with lactic acid bacteria (LAB) contributed to the improved biological value of lentils; still, the quantity of BA needs to be considered. Further investigations into the P. acidilactici metabolism of certain compounds (such as phenolic and antinutritional compounds) in lentils during fermentation ought to be carried out.

Enhanced removal of rare earth elements from aqueous media: exploring the potential of AM-3 and AM-4 titanosilicates.

This study investigates the impact of three key variables on the performance of nanoporous AM-3 and layered AM-4 titanosilicates in removing nine REEs (Y, La, Ce, Pr, Nd, Eu, Gd, Tb, and Dy) from natural mineral water and identifies optimal operational conditions using Response Surface Methodology (RSM). The experimental conditions were determined by a Box-Behnken Design of 3 factors-3 levels (pH 4, 6, and 8; sorbent dose 20, 100, and 180 mg/L; and element concentration 1, 3, and 5 µmol/L). Three-dimensional response surfaces were used to assess the linear, quadratic, and interaction influences of each factor on the REEs' removal percentage. The pH was the most significant factor in the removal process using AM-3, while the sorbent dose was more important for AM-4. The results highlighted the sorbents' strong capacity for REE removal. The optimal operating conditions obtained by RSM were applied to aqueous solutions with salinity 10 (common in coastal and transitional systems) and 30 (average seawater salinity). The results showed that AM-3 has a strong potential for removing REEs in solutions with salinity 10 and 30, while AM-4 was less efficient due to competition between REEs and other ions present in the solution.

Tumor mutational burden in colorectal cancer: Implications for treatment.

Although immune checkpoint inhibitors have revolutionized the treatment of several advanced solid cancers, in colorectal cancer, the transformative benefit of these innovative medicines is currently limited to those with deficient mismatch repair or high microsatellite instability. Tumor mutational burden (TMB) has emerged as a potential predictor of immunotherapy benefit, but the lack of standardization in its assessment and reporting has hindered the introduction of this biomarker in routine clinical practice. Here, we compiled 45 colorectal cancer studies utilizing numerical thresholds for high-TMB. In this group of studies, TMB cut-offs ranged from 6.88 to 41 mut/Mb and were most often set at 10, 17, or 20 mut/Mb. Additionally, we observed divergent TMB definitions and inconsistent disclosure of specific methodological details, which collectively emphasize the substantial lack of harmonization within the field. Ongoing efforts to harmonize TMB assessment will be critical to validate TMB as a predictive marker of immunotherapy response.

Green manure (Crotalaria juncea L.) enhances Origanum vulgare L. biomass accumulation, essential oil yield, and phytochemical properties.

Green manure (GM) may reduce the use of chemical fertilizers, been an ecologically appropriate strategy to cultivation of medicinal plants. Crotalaria juncea, is one of the most used because it adapts to different climatic and high nitrogen content. Origanum vulgare. is widely used in cooking, pharmaceutical, cosmetic industries and food products. The objectives of this study were to evaluate the GM on biomass, essential oil (EO), phenolic and antioxidant. The experiment consisted: control; 150, 300, 450, and 600 g (Sh= leaves+steam) more 200 g roots (R); 600 g aerial part; 200 g roots; and soil with 300 g cattle manure per pot. The highest dry weights were observed in the presence of GM and cattle manure (90 days). The control had an EO production 75% lower in relation to the dose of 450 g GM (Sh+R). Principal component analysis showed that GM and cattle manure positively influenced the dry weight, content, yield, and EO constituents, and total flavonoids. The GM contributed to the accumulation of the major EO compounds (trans-sabinene hydrate, thymol, terpinen-4-ol). The GM management may be beneficial for cultivating, because it can increase the production of biomass and the active components, in addition to being an inexpensive resource.

Whole Genome Analysis of Tibetan Kefir-Derived Lactiplantibacillus Plantarum 12-3 Elucidates Its Genomic Architecture, Antimicrobial and Drug Resistance, Potential Probiotic Functionality and Safety.

BACKGROUND: Lactiplantibacillus plantarum 12-3 holds great promise as a probiotic bacterial strain, yet its full potential remains untapped. This study aimed to better understand this potential therapeutic strain by exploring its genomic landscape, genetic diversity, CRISPR-Cas mechanism, genotype, and mechanistic perspectives for probiotic functionality and safety applications. METHODS: L. plantarum 12-3 was isolated from Tibetan kefir grains and, subsequently, Illumina and Single Molecule Real-Time (SMRT) technologies were used to extract and sequence genomic DNA from this organism. After performing pan-genomic and phylogenetic analysis, Average Nucleotide Identity (ANI) was used to confirm the taxonomic identity of the strain. Antibiotic resistance gene analysis was conducted using the Comprehensive Antibiotic Resistance Database (CARD). Antimicrobial susceptibility testing, and virulence gene identification were also included in our genomic analysis to evaluate food safety. Prophage, genomic islands, insertion sequences, and CRISPR-Cas sequence analyses were also carried out to gain insight into genetic components and defensive mechanisms within the bacterial genome. RESULTS: The 3.4 Mb genome of L. plantarum 12-3, was assembled with 99.1% completeness and low contamination. A total of 3234 genes with normal length and intergenic spacing were found using gene prediction tools. Pan-genomic studies demonstrated gene diversity and provided functional annotation, whereas phylogenetic analysis verified taxonomic identity. Our food safety study revealed a profile of antibiotic resistance that is favorable for use as a probiotic. Analysis of insertional sequences, genomic islands, and prophage within the genome provided information regarding genetic components and their possible effects on evolution. CONCLUSIONS: Pivotal genetic elements uncovered in this study play a crucial role in bacterial defense mechanisms and offer intriguing prospects for future genome engineering efforts. Moreover, our findings suggest further in vitro and in vivo studies are warranted to validate the functional attributes and probiotic potential of L. plantarum 12-3. Expanding the scope of the research to encompass a broader range of L. plantarum 12-3 strains and comparative analyses with other probiotic species would enhance our understanding of this organism's genetic diversity and functional properties.

Blood count, endocrine, immunologic, renal, and hepatic markers in a case-control animal study of induced periodontitis in female rodents.

Introduction: Periodontitis is a non-communicable chronic inflammatory disease with a systemic burden. Animal models of induced periodontitis help elucidate the mechanisms by which periodontal inflammation drives systemic effects. Studying this systemic involvement over longer follow-up periods may provide a strong foundation for future research on the association between diseases and periodontitis, particularly in female rats. Therefore, we aimed to compare blood, endocrine, immunologic, renal, and hepatic markers in a rat model of induced periodontitis in females with their control counterparts. Methods: Experimental periodontitis was induced in 20 female Wistar rats by the application and maintenance of silk ligatures on the upper molars. The rats were then assessed for macroscopical analysis, complete blood count, and biochemical, endocrine, and immunologic markers at 21, 28, 42, and 56 days. Results: Chronic periodontal inflammation was observed after 42 days of exposure to the ligatures. Additionally, it was also possible to notice significant systemic manifestations, such as the reduction of triiodothyronine and thyroxine levels, along with an increase in the expression of alkaline phosphatase, gamma-glutamyl transpeptidase, and lactate dehydrogenase. Discussion: The study's findings imply that certain changes can be underscored to highlight a reduced risk of conception. Notably, previous investigations have indicated that subfertile women exhibit lower levels of thyroid hormones and elevated lactate dehydrogenase expression. Despite the absence of preclinical data delineating a possible association between periodontitis and female infertility, the results of this study may prove to be a crucial contribution to both the scientific and medical fields.

Harnessing Brazilian biodiversity database: identification of flavonoids as potential inhibitors of SARS-CoV-2 main protease using computational approaches and all-atom molecular dynamics simulation.

SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) is the etiological agent responsible for the global outbreak of COVID-19 (Coronavirus Disease 2019). The main protease of SARS-CoV-2, Mpro, is a key enzyme that plays a vital role in mediating viral replication and transcription. In this study, a comprehensive computational approach was employed to investigate the binding affinity, selectivity, and stability of natural product candidates as potential new antivirals acting on the viral polyprotein processing mediated by SARS-CoV-2 Mpro. A library of 288 flavonoids extracted from Brazilian biodiversity was screened to select potential Mpro inhibitors. An initial filter based on Lipinski's rule of five was applied, and 204 compounds that did not violate any of the Lipinski rules were selected. The compounds were then docked into the active site of Mpro using the GOLD program, and the poses were subsequently re-scored using MM-GBSA (Molecular Mechanics Generalized Born Surface Area) binding free energy calculations performed by AmberTools23. The top five flavonoids with the best MM-GBSA binding free energy values were selected for analysis of their interactions with the active site residues of the protein. Next, we conducted a toxicity and drug-likeness analysis, and non-toxic compounds were subjected to molecular dynamics simulation and free energy calculation using the MM-PBSA (Molecular Mechanics Poisson-Boltzmann Surface Area) method. It was observed that the five selected flavonoids had lower MM-GBSA binding free energy with Mpro than the co-crystal ligand. Furthermore, these compounds also formed hydrogen bonds with two important residues, Cys145 and Glu166, in the active site of Mpro. Two compounds that passed the drug-likeness filter showed stable conformations during the molecular dynamics simulations. Among these, NuBBE_867 exhibited the best MM-PBSA binding free energy value compared to the crystallographic inhibitor. Therefore, this study suggests that NuBBE_867 could be a potential inhibitor against the main protease of SARS-CoV-2 and may be further examined to confirm our results.

An Integrated Approach to the Anti-Inflammatory, Antioxidant, and Genotoxic Potential of Portuguese Traditional Preparations from the Bark of Anacardium occidentale L.

Anacardium occidentale L. stem bark Traditional Herbal Preparations (AoBTHPs) are widely used in traditional medicine to treat inflammatory conditions, such as diabetes. The present study aims to evaluate the anti-inflammatory, antioxidant, and genotoxic potential of red and white Portuguese AoBTHPs. Using a carrageenan-induced rat paw edema model, a significant anti-edema effect was observed for all tested doses of white AoBTHP (40.2, 71.5, and 127.0 mg/kg) and the two highest doses of red AoB THP (71.5 and 127.0 mg/kg). The anti-edema effect of red AoBTHP's highest dose was much more effective than indomethacin 10 mg/kg, Trolox 30 mg/kg, and Tempol 30 mg/kg. In DPPH, FRAP, and TAC using the phosphomolybdenum method, both types of AoBTHPs showed similar antioxidant activity and no genotoxicity up to 5000 µg/plate in the Ames test. The LC-UV/DAD-ESI/MS fingerprint allowed the identification of gallic and protocatechuic acids as the two main marker compounds and the presence of catechin, epicatechin, epigallocatechin gallate, and ellagic acid in both AoBTHPs. The obtained results support the validation of red and white AoB and their THPs as anti-inflammatory agents and contribute to the possible development of promising new therapeutic options to treat inflammatory conditions.

Exploring the Luminescence, Redox, and Magnetic Properties in a Multivariate Metal-Organic Radical Framework.

Persistent neutral organic radicals are excellent building blocks for the design of functional molecular materials due to their unique electronic, magnetic, and optical properties. Among them, triphenylmethyl radical derivatives have attracted a lot of interest as luminescent doublet emitters. Although neutral organic radicals have been underexplored as linkers for building metal-organic frameworks (MOFs), they hold great potential as organic elements that could introduce additional electronic properties within these frameworks. Herein, we report the synthesis and characterization of a novel multicomponent metal-organic radical framework (PTMTCR@NR-Zn MORF), which is constructed from the combination of luminescent perchlorotriphenylmethyl tricarboxylic acid radical (PTMTCR) and nonemissive nonradical (PTMTCNR) organic linkers and Zn(II) ions. The PTMTCR@NR-Zn MORF structure is layered with microporous one-dimensional channels embedded within these layers. Kelvin probe force microscopy further confirmed the presence of both organic nonradical and radical linkers in the framework. The luminescence properties of the PTMTCR ligand (first studied in solution and in the solid state) were maintained in the radical-containing PTMTCR@NR-Zn MORF at room temperature as fluorescence solid-state quenching is suppressed thanks to the isolation of the luminescent radical linkers. In addition, magnetic and electrochemical properties were introduced to the framework due to the incorporation of the paramagnetic organic radical ligands. This work paves the way for the design of stimuli-responsive hybrid materials with tunable luminescence, electrochemical, and magnetic properties by the proper combination of closed- and open-shell organic linkers within the same framework.