Metastatic organotropism: a brief overview.

Organotropism has been known since 1889, yet this vital component of metastasis has predominantly stayed elusive. This mini-review gives an overview of the current understanding of the underlying mechanisms of organotropism and metastases development by focusing on the formation of the pre-metastatic niche, immune defenses against metastases, and genomic alterations associated with organotropism. The particular case of brain metastases is also addressed, as well as the impact of organotropism in cancer therapy. The limited comprehension of the factors behind organotropism underscores the necessity for efficient strategies and treatments to manage metastases.

WITHANICANDRIN ISOLATED FROM Datura Ferox PROMOTES ANTINOCICEPTION BY MODULATING THE ASICS AND TRPS CHANNELS AND ANTI-INFLAMMATION IN ADULT ZEBRAFISH.

This is the first study to analyze the anti-inflammatory and antinociceptive effect of withanicandrin, isolated from Datura Ferox leaves, and the possible mechanism of action involved in adult zebrafish (ZFa). To this end, the animals were treated intraperitoneally (i.p.) with withanicandrin (4; 20 and 40 mg/kg; 20 µL) and subjected to locomotor activity and acute toxicity. Nociception tests were also carried out with chemical agents, in addition to tests to evaluate inflammatory processes induced by κ-Carrageenan 1.5% and a Molecular Docking study. As a result, withanicandrin reduced nociceptive behavior by capsaicin at a dose of 40 mg/kg and by acid saline at doses of 4 and 40 mg/kg, through neuromodulation of TRPV1 channels and ASICs, identified through blocking the antinociceptive effect of withanicandrin by the antagonists capsazepine and naloxone. Furthermore, withanicandrin caused an anti-inflammatory effect through the reduction of abdominal edema, absence of leukocyte infiltrate in the liver tissue and reduction of ROS in thel liver tissue and presented better affinity energy compared to control morphine (TRPV1) and ibuprofen (COX-1 and COX-2).

Further polycyclic quinones of Micromonospora sp.

The crude acetone extract of a marine Micromonospora sp. strain associated with Eudistoma vannnamei was fractioned with hexane and ethyl acetate. The crude extract and both soluble fractions were assayed against several bacteria strains. The new polycyclic quinones 12-hydroxy-9-propyltetracene-6,1-dione (1), 5,12-dihydroxy-4-methoxy-9-propyltetracene-5,12-dione (2), and  4,6-dihydroxy-3-methoxycarbonyl- methyl-6a-(oxobutyl)-5,12-anthraquinone (3), along with the known 4,6-dihydroxy-3-methoxycarbonyl-methyl-6a-(oxo-3-methyl-butyl)-5,12-anthraquinone (4) and 4,6-dihydroxy-3-methoxycarbonyl-methyl-6a-(oxopentyl)-5,12-anthraquinone (5) were isolated from the hexane-soluble fraction, while from the active ethyl acetate fraction were isolated the known 4,6,11-trihydroxy-9-propyltetracene-5,12-dione (6), 4-methoxy-9-propyltetracene-6,11-dione (7), 7,8,9,10-tetrahydro-9-hydroxy-4-methoxy-9-propyltetracene-6,11-dione (8), and 10b-carbomethoxy-7,8,9,10-tetrahydro-4,6,7a,9a,11-pentahydroxy-9-propyltetracene-5,12-dione (9). The structures of the new compounds were established by interpretation of HRMS and NMR techniques.  A study of molecular docking was performed with the compounds from the active ethyl acetate fraction to correlate tentatively with the antimicrobial activity.  Molecular docking, RMSD, RMSF, and MM-GBSA evaluations were performed to investigate the inhibitory activity of 6-8 against the protein PDB-codex 1MWT, being considered a promising target for studying drug development responsible for inhibiting replication of Staphylococcus aureus. Penicillin G was used as the standard inhibitory. Anthracyclinones 6-8 were the best hydrolase inhibitor with affinity energy -8.1 to -7.9 kcal/mol compared to penicillin G, which presented -6.9 kcal/mol.

Petrosamine isolated from marine sponge Petrosia sp. demonstrates protection against neurotoxicity in vitro and in vivo.

According to The World Alzheimer Report 2023 by Alzheimer's Disease International (ADI) estimates that 33 to 38.5 million people worldwide suffer from Alzheimer's Disease (AD). A crucial hallmark associated with this disease is associated with the deficiency of the brain neurotransmitter acetylcholine, due to an affected acetylcholinesterase (AChE) activity. Marine organisms synthesize several classes of compounds, some of which exhibit significant AChE inhibition, such as petrosamine, a coloured pyridoacridine alkaloid. The aim of this work was to characterize the activity of petrosamine isolated for the first time from a Brazilian marine sponge, using two neurotoxicity models with aluminium chloride, as exposure to aluminium is associated with the development of neurodegenerative diseases. The in vitro model was based in a neuroblastoma cell line and the in vivo model exploited the potential of zebrafish (Danio rerio) embryos in mimicking hallmarks of AD. To our knowledge, this is the first report on petrosamine's activity over these parameters, either in vitro or in vivo, in order to characterize its full potential for tackling neurotoxicity.

Al/SBA-15 Mesoporous Material: A Study of pH Influence over Aluminum Insertion into the Framework.

Herein, ordered mesoporous materials like SBA-15 and Al/SBA-15 were prepared using the pH adjustment method. Thus, these materials were developed in different pH of synthesis, from the pH adjustment method using a KCl/HCl solution and varying the Si/Al molar ratio (5, 25, and 75). All the ordered mesoporous materials were characterized by FRX, 27Al NMR, SEM, XRD, N2 adsorption/desorption, and CO2 adsorption. From the applied method, it was possible to obtain SBA-15 and Al/SBA-15 with high mesoscopic ordering based on the XRD patterns, independent of the pH employed. From the chemical composition, the insertion of higher amounts of Al into the synthesis caused a progressive improvement in the structural and textural properties of the ordered mesoporous materials. Thus, the chosen synthesis conditions can lead to different aluminum coordination (tetrahedral and octahedral), which gives these materials a greater potential to be applied. The presence of Al in high amounts provides material with the ability to form micropores. Finally, the proposed method proved to be innovative; low-cost; less aggressive to the environment, with efficient insertion of aluminum in the framework of SBA-15 mesoporous material; and practical, based on only one step.

Screening of alkaloids and withanolides isolated from Solanaceae plants for antifungal properties against non-wild type Sporothrix brasiliensis.

Antifungal resistance has often been found in animal sporotrichosis in Southern Brazil. The biological potential of compounds from plants of the Solanaceae family against infectious diseases is known, however, it is still unknown against Sporothrix brasiliensis. This study evaluated the anti-Sporothrix brasiliensis activity, synergism, cytotoxicity, and action mechanism of steroidal lactones (withanolides) and alkaloids isolated from these plants. Pure compounds of withanolide D (WNOD), physalin F (PHYF), withanicandin (WNIC), nicandin B (NICB), solasonine (SSON), and solamargine (SMAR) were tested against 12 Sporothrix brasiliensis isolated from cats (n = 11) and dogs (n = 2) through M38-A2 CLSI. For the compounds with the best activity, a checkerboard assay for synergism, sorbitol protection, and ergosterol effect for action mechanism; and MTT test for cytotoxicity were performed. The withanolides WNOD, PHYF, WNIC, and NICB were not antifungal, but SSON (MIC 0.125-1 mg/mL) and SMAR (MIC 0.5-1 mg/mL) were both fungistatic and fungicidal (MFC 0.5-1 mg/mL for both) against wild-type (WT) and non-WT isolates. The activity of SSON and SMAR was indifferent when combined with itraconazole. In the mechanism of action, cell wall and plasma membrane by complexation with ergosterol seemed to be two target structures of SSON and SMAR. SSON was selected for cytotoxicity, whose cell viability in MDBK cells ranged from 28.85 % to 101.75 %, and was higher than 87.49 % at concentrations ≤0.0015 mg/ml. Only the steroidal alkaloids SSON and SMAR were active against non-WT isolates, being promising antifungal candidates for the treatment of feline and canine sporotrichosis with low susceptibility to itraconazole.

Comparison of Direct Repair Versus Anatomic Graft Reconstruction of the Anterior Talofibular Ligament: A Biomechanical Cadaveric Study.

The goal of our study is to compare the stability of the anatomic reconstruction of the anterior talofibular ligament (ATFL) with direct repair of the ATFL, in a cadaver model. We performed the following techniques in 18 cadaveric ankles: the intact ATFL was cut, after which a direct repair using 2 anchors was performed. The repair was sectioned, and anatomic reconstruction was then performed with a tendon autograft. We measured angular displacement in 3 anatomic planes (axial, coronal, sagittal) for each situation in response to the anterior drawer test (ADT), talar tilt test (TTT) and pivot test (PT), using a specifically constructed arthrometer. The sectioned ATFL was inferior to the intact ATFL in the axial plane with the ADT (p = .012), in the axial plane with the PT (p = .001) and in the axial and coronal planes with the TTT (p = .013 and p = .016, respectively). Direct anatomic repair was inferior to the intact ATFL in the axial plane upon the PT (p = .009). No differences could be found between anatomic graft reconstructions and the intact ATFL with any manoeuver, nor when comparing anatomic graft reconstruction and direct repair with 2 anchors. We were able to conclude that anatomic graft reconstruction of the ATFL reproduces angular stability of the native ligament in a cadaver model. While we could not detect if anatomic graft reconstruction was superior to direct repair, the latter proved to be less stable in the axial plane upon internal rotation (pivot test) versus the intact ATFL.

Asymmetric post-translational modifications regulate the nuclear translocation of STAT3 homodimers in response to leukemia inhibitory factor.

STAT3 is a pleiotropic transcription factor overactivated in 70% of solid tumours. We have recently reported that inactivating mutations on residues susceptible to post-translational modifications (PTMs) in only one of the monomers (i.e. asymmetric) caused changes in the cellular distribution of STAT3 homodimers. Here, we used more controlled experimental conditions, i.e. without the interference of endogenous STAT3 (STAT3-/- HeLa cells) and in the presence of a defined cytokine stimulus (Leukemia Inhibitory Factor, LIF), to provide further evidence that asymmetric PTMs affect the nuclear translocation of STAT3 homodimers. Time-lapse microscopy for 20 min after LIF stimulation showed that S727 dephosphorylation (S727A) and K685 inactivation (K685R) slightly enhanced the nuclear translocation of STAT3 homodimers, while K49 inactivation (K49R) delayed STAT3 nuclear translocation. Our findings suggest that asymmetrically modified STAT3 homodimers could be a new level of STAT3 regulation and, therefore, a potential target for cancer therapy.

Reconstruction of the interosseous talocalcaneal ligament using allograft for subtalar joint stabilization is effective.

PURPOSE: The aim of this study was to assess the biomechanical effects of subtalar ligament injury and reconstruction on stability of the subtalar joint in all three spatial planes. METHODS: Fifteen fresh frozen cadaveric legs were used, with transfixed tibiotalar joints to isolate motion to the subtalar joint. An arthrometer fixed to the lateral aspect of the calcaneus measured angular displacement in all three spatial planes on the inversion and eversion stress tests. Stress manoeuvres were tested with the intact joint, and then repeated after sequentially sectioning the inferior extensor retinaculum (IER), cervical ligament (CL), interosseous talocalcaneal ligament (ITCL), arthroscopic graft reconstruction of the ITCL, and sectioning of the calcaneo-fibular ligament (CFL). RESULTS: Sectioning the ITCL significantly increased angular displacement upon inversion and eversion in the coronal and sagittal planes. Reconstruction of the ITCL significantly improved angular stability against eversion in the axial and sagittal planes, and against inversion in the axial and coronal planes, at the zero time point after reconstruction. After sectioning the CFL, resistance to eversion decreased significantly in all three planes. CONCLUSION: Progressive injury of ligamentous stabilisers, particularly the ITCL, led to increasing angular displacement of the subtalar joint measured with the inversion and eversion stress tests, used in clinical practice. Reconstruction of the ITCL using tendon graft significantly stabilised the subtalar joint in the axial and sagittal planes against eversion and in the axial and coronal planes against inversion, immediately after surgery.

Analysis of asymptomatic Drosophila models for ALS and SMA reveals convergent impact on functional protein complexes linked to neuro-muscular degeneration.

BACKGROUND: Spinal Muscular Atrophy (SMA) and Amyotrophic Lateral Sclerosis (ALS) share phenotypic and molecular commonalities, including the fact that they can be caused by mutations in ubiquitous proteins involved in RNA metabolism, namely SMN, TDP-43 and FUS. Although this suggests the existence of common disease mechanisms, there is currently no model to explain the resulting motor neuron dysfunction. In this work we generated a parallel set of Drosophila models for adult-onset RNAi and tagged neuronal expression of the fly orthologues of the three human proteins, named Smn, TBPH and Caz, respectively. We profiled nuclear and cytoplasmic bound mRNAs using a RIP-seq approach and characterized the transcriptome of the RNAi models by RNA-seq. To unravel the mechanisms underlying the common functional impact of these proteins on neuronal cells, we devised a computational approach based on the construction of a tissue-specific library of protein functional modules, selected by an overall impact score measuring the estimated extent of perturbation caused by each gene knockdown. RESULTS: Transcriptome analysis revealed that the three proteins do not bind to the same RNA molecules and that only a limited set of functionally unrelated transcripts is commonly affected by their knock-down. However, through our integrative approach we were able to identify a concerted effect on protein functional modules, albeit acting through distinct targets. Most strikingly, functional annotation revealed that these modules are involved in critical cellular pathways for motor neurons, including neuromuscular junction function. Furthermore, selected modules were found to be significantly enriched in orthologues of human neuronal disease genes. CONCLUSIONS: The results presented here show that SMA and ALS disease-associated genes linked to RNA metabolism functionally converge on neuronal protein complexes, providing a new hypothesis to explain the common motor neuron phenotype. The functional modules identified represent promising biomarkers and therapeutic targets, namely given their alteration in asymptomatic settings.

Night-time warming in the field reduces nocturnal stomatal conductance and grain yield but does not alter daytime physiological responses.

Global nocturnal temperatures are rising more rapidly than daytime temperatures and have a large effect on crop productivity. In particular, stomatal conductance at night (gsn ) is surprisingly poorly understood and has not been investigated despite constituting a significant proportion of overall canopy water loss. Here, we present the results of 3 yr of field data using 12 spring Triticum aestivum genotypes which were grown in NW Mexico and subjected to an artificial increase in night-time temperatures of 2°C. Under nocturnal heating, grain yields decreased (1.9% per 1°C) without significant changes in daytime leaf-level physiological responses. Under warmer nights, there were significant differences in the magnitude and decrease in gsn , values of which were between 9 and 33% of daytime rates while respiration appeared to acclimate to higher temperatures. Decreases in grain yield were genotype-specific; genotypes categorised as heat tolerant demonstrated some of the greatest declines in yield in response to warmer nights. We conclude the essential components of nocturnal heat tolerance in wheat are uncoupled from resilience to daytime temperatures, raising fundamental questions for physiological breeding. Furthermore, this study discusses key physiological traits such as pollen viability, root depth and irrigation type may also play a role in genotype-specific nocturnal heat tolerance.

Satellite imagery for high-throughput phenotyping in breeding plots.

Advances in breeding efforts to increase the rate of genetic gains and enhance crop resilience to climate change have been limited by the procedure and costs of phenotyping methods. The recent rapid development of sensors, image-processing technology, and data-analysis has provided opportunities for multiple scales phenotyping methods and systems, including satellite imagery. Among these platforms, satellite imagery may represent one of the ultimate approaches to remotely monitor trials and nurseries planted in multiple locations while standardizing protocols and reducing costs. However, the deployment of satellite-based phenotyping in breeding trials has largely been limited by low spatial resolution of satellite images. The advent of a new generation of high-resolution satellites may finally overcome these limitations. The SkySat constellation started offering multispectral images at a 0.5 m resolution since 2020. In this communication we present a case study on the use of time series SkySat images to estimate NDVI from wheat and maize breeding plots encompassing different sizes and spacing. We evaluated the reliability of the calculated NDVI and tested its capacity to detect seasonal changes and genotypic differences. We discuss the advantages, limitations, and perspectives of this approach for high-throughput phenotyping in breeding programs.

Campesterol Semi-Synthetic Derivatives as Potential Antibacterial: in†vitro and in silico Evaluation.

In this study, twelve campesterol derivatives (2-13) were prepared by esterification reaction at the hydroxy group in C-3 and catalytic hydrogenation at the carbon-carbon double bond in C-5(6). All obtained compounds were characterized by IR, 1 H-NMR, 13 C-NMR, and MS spectra. Campesterol (1) and its derivatives (2-13) were evaluated in vitro against Staphylococcus aureus (ATCC 6538), Streptococcus mutans (ATCC 0046), Escherichia coli (ATCC 10536), Pseudomonas aeruginosa (ATCC 15442), and Klebsiella pneumoniae (ATCC 10031) using the microdilution method. Among tested compounds, 4, 6, 9, 11, 12, and 13 displayed the best antibacterial activity. Moreover, to support the antibacterial activity experiments, the investigation of molecular interactions of more active compounds, and also compound 1 and neomycin, used as starting material and positive control, respectively, at the binding site of the target proteins was performed using molecular docking simulations. Four compounds (7, 9, 10 and 11) are herein described for the first time.

Multi-modal deep learning improves grain yield prediction in wheat breeding by fusing genomics and phenomics.

MOTIVATION: Developing new crop varieties with superior performance is highly important to ensure robust and sustainable global food security. The speed of variety development is limited by long field cycles and advanced generation selections in plant breeding programs. While methods to predict yield from genotype or phenotype data have been proposed, improved performance and integrated models are needed. RESULTS: We propose a machine learning model that leverages both genotype and phenotype measurements by fusing genetic variants with multiple data sources collected by unmanned aerial systems. We use a deep multiple instance learning framework with an attention mechanism that sheds light on the importance given to each input during prediction, enhancing interpretability. Our model reaches 0.754 ± 0.024 Pearson correlation coefficient when predicting yield in similar environmental conditions; a 34.8% improvement over the genotype-only linear baseline (0.559 ± 0.050). We further predict yield on new lines in an unseen environment using only genotypes, obtaining a prediction accuracy of 0.386 ± 0.010, a 13.5% improvement over the linear baseline. Our multi-modal deep learning architecture efficiently accounts for plant health and environment, distilling the genetic contribution and providing excellent predictions. Yield prediction algorithms leveraging phenotypic observations during training therefore promise to improve breeding programs, ultimately speeding up delivery of improved varieties. AVAILABILITY AND IMPLEMENTATION: Available at https://github.com/BorgwardtLab/PheGeMIL (code) and https://doi.org/doi:10.5061/dryad.kprr4xh5p (data).

The Role of Sperm Membrane Potential and Ion Channels in Regulating Sperm Function.

During the last seventy years, studies on mammalian sperm cells have demonstrated the essential role of capacitation, hyperactivation and the acrosome reaction in the acquisition of fertilization ability. These studies revealed the important biochemical and physiological changes that sperm undergo in their travel throughout the female genital tract, including changes in membrane fluidity, the activation of soluble adenylate cyclase, increases in intracellular pH and Ca2+ and the development of motility. Sperm are highly polarized cells, with a resting membrane potential of about -40 mV, which must rapidly adapt to the ionic changes occurring through the sperm membrane. This review summarizes the current knowledge about the relationship between variations in the sperm potential membrane, including depolarization and hyperpolarization, and their correlation with changes in sperm motility and capacitation to further lead to the acrosome reaction, a calcium-dependent exocytosis process. We also review the functionality of different ion channels that are present in spermatozoa in order to understand their association with human infertility.

Multimodal deep learning methods enhance genomic prediction of wheat breeding.

While several statistical machine learning methods have been developed and studied for assessing the genomic prediction (GP) accuracy of unobserved phenotypes in plant breeding research, few methods have linked genomics and phenomics (imaging). Deep learning (DL) neural networks have been developed to increase the GP accuracy of unobserved phenotypes while simultaneously accounting for the complexity of genotype-environment interaction (GE); however, unlike conventional GP models, DL has not been investigated for when genomics is linked with phenomics. In this study we used 2 wheat data sets (DS1 and DS2) to compare a novel DL method with conventional GP models. Models fitted for DS1 were GBLUP, gradient boosting machine (GBM), support vector regression (SVR) and the DL method. Results indicated that for 1 year, DL provided better GP accuracy than results obtained by the other models. However, GP accuracy obtained for other years indicated that the GBLUP model was slightly superior to the DL. DS2 is comprised only of genomic data from wheat lines tested for 3 years, 2 environments (drought and irrigated) and 2-4 traits. DS2 results showed that when predicting the irrigated environment with the drought environment, DL had higher accuracy than the GBLUP model in all analyzed traits and years. When predicting drought environment with information on the irrigated environment, the DL model and GBLUP model had similar accuracy. The DL method used in this study is novel and presents a strong degree of generalization as several modules can potentially be incorporated and concatenated to produce an output for a multi-input data structure.

Uncertainty Quantification in Constitutive Models of Highway Bridge Components: Seismic Bars and Elastomeric Bearings.

Bridges are essential structures in the logistic chain of countries, making it critical to design them to be as resilient as possible. One way to achieve this is through performance-based seismic design (PBSD), which involves using nonlinear Finite Element (FE) models to predict the response and potential damage of different structural components under earthquake excitations. Nonlinear FE models need accurate constitutive models of material and components. Among them, seismic bars and laminated elastomeric bearings play an important role in a bridge's response to earthquakes; therefore, properly validated and calibrated models should be proposed. Only default parameter values from the early development of the constitutive models widely used by researchers and practitioners for these components tend to be used, and low identifiability of its governing parameters and the high cost of generating reliable experimental data have prevented a thorough probabilistic characterization of their model parameters. To address this issue, this study implements a Bayesian probabilistic framework using Sequential Monte Carlo (SMC) for updating the parameters of constitutive models of seismic bars and elastomeric bearings and proposes joint probability density functions (PDF) for the most influential parameters. The framework is based on actual data from comprehensive experimental campaigns. The PDFs are obtained from independent tests conducted on different seismic bars and elastomeric bearings, to then consolidate all the information in a single PDF for each modeling parameter by means of the conflation methodology, where the mean, coefficient of variation, and correlation between calibrated parameters are obtained for each bridge component. Finally, findings show that the incorporation of model parameter uncertainty through a probabilistic framework will allow for a more accurate prediction of the response of bridges under strong earthquakes.

Exotic alleles contribute to heat tolerance in wheat under field conditions.

Global warming poses a major threat to food security and necessitates the development of crop varieties that are resilient to future climatic instability. By evaluating 149 spring wheat lines in the field under yield potential and heat stressed conditions, we demonstrate how strategic integration of exotic material significantly increases yield under heat stress compared to elite lines, with no significant yield penalty under favourable conditions. Genetic analyses reveal three exotic-derived genetic loci underlying this heat tolerance which together increase yield by over 50% and reduce canopy temperature by approximately 2 °C. We identified an Ae. tauschii introgression underlying the most significant of these associations and extracted the introgressed Ae. tauschii genes, revealing candidates for further dissection. Incorporating these exotic alleles into breeding programmes could serve as a pre-emptive strategy to produce high yielding wheat cultivars that are resilient to the effects of future climatic uncertainty.

Female Infertility Is Associated with an Altered Expression Profile of Different Members of the Tachykinin Family in Human Granulosa Cells.

Neurokinin B (NKB) and its cognate receptor, NK3R, play a key role in the regulation of reproduction. NKB belongs to the family of tachykinins, which also includes substance P and neurokinin A, both encoded by the by the gene TAC1, and hemokinin-1, encoded by the TAC4 gene. In addition to NK3R, tachykinin effects are mediated by NK1R and NK2R, encoded by the genes TACR1 and TACR2, respectively. The role of these other tachykinins and receptors in the regulation of women infertility is mainly unknown. We have analyzed the expression profile of TAC1, TAC4, TACR1, and TACR2 in mural granulosa and cumulus cells from women presenting different infertility etiologies, including polycystic ovarian syndrome, advanced maternal age, low ovarian response, and endometriosis. We also studied the expression of MME, the gene encoding neprilysin, the most important enzyme involved in tachykinin degradation. Our data show that TAC1, TAC4, TACR1, TACR2, and MME expression is dysregulated in a different manner depending on the etiology of women infertility. The abnormal expression of these tachykinins and their receptors might be involved in the decreased fertility of these patients, offering a new insight regarding the diagnosis and treatment of women infertility.

Hypoglycemic and hepatoprotective effects in adult zebrafish (Danio rerio) of fisetinidol isolated from Bauhinia pentandra: In vivo and in silico assays.

Diabetes mellitus is a chronic metabolic disorder that has been increasing drastically around the worldwide. It is important to emphasize that although many drugs are commercially available to treat diabetes, many of them have shown a number of adverse effects. Therefore, search for new antidiabetic agents is of great interest, and natural products, especially those obtained from plants sources, may be an alternative to available drugs. This study reports the in vivo and in silico evaluation of the hypoglycemic activity of fisetinidol. The conformational analysis confirmed that the fisetinidol compound possesses two valleys in the potential energy curve, showing a stable conformer on the global minimum of the PES defined by the dihedral angle θ (C6-C7-O-H) at 179.9°, whose energy is equal to zero. In addition, fisetinidol has shown promise in glycemic control and oxidative stress caused by hyperglycemia induced by high sucrose concentration, causing hypoglycemic and hepatoprotective effects in adult zebrafish. ADMET studies showed that fisetinidol has high passive permeability, low clearance and low toxic risk by ingestion, and computational studies demonstrated that fisetinidol complexes in the same region as metformin and α-acarbose, which constitutes a strong indication that fisetinidol has the same inhibitory mechanisms of α-acarbose and metformin.Communicated by Ramaswamy H. Sarma.