ICB - Artigos publicados em periódicos

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Validation of an SNP marker associated with resistance to common bacterial blight in common bean (Phaseolus vulgaris L.)
(2025) Coelho, Laysla Morais; Messias, Lucas Matias Gomes; Santos, Ana Rubia de Sá; Torga, Nayana Valéria Costa Paula Pereira; Costa, Joaquim Geraldo Caprio da; Pereira, Helton Santos; Vianello, Rosana Pereira; Souza, Thiago Lívio Pessoa Oliveira de
Marker-assisted selection (MAS) can be an alternative to rapidly select and develop genotypes resistant to common bacterial blight (CBB), a disease that severely impacts common bean production. The aim of this study was to use MAS to evaluate and validate the SNP marker snpPV0039, already identified as linked to the CBB resistance locus SU91, in selection of common bean genotypes that carry the resistance allele. We evaluated a diverse panel of 56 common bean genotypes with different levels of reaction to CBB, as well as 218 F2 plants that had the variety CB911921, resistant to CBB, as a parent. The F2 plants were evaluated regarding their reaction to the pathogen Xanthomonas phaseoli, isolate CNF19 (Xap strain). The snpPV0039 marker amplified the resistance allele associated with QTLSU91 in the main sources of CBB resistance. In addition, a segregation ratio of 1RR:2Rr:1rr was observed, with a recombination frequency of 8.74 cM of the QTLSU91 and a selection efficiency of 96.94%. Based on these results, incorporation of the snpPV0039 marker in the marker-assisted selection routine in the common bean breeding program is strongly recommended.
Long-term preserved bean seeds exhibit high RNA integrity and high germination potential
(2025) Dantas, Alisson Ferreira; Nunes, Tayara Colins; Grynberg, Priscila; Brasileiro, Ana Cristina Miranda; Salomão, Antonieta Nassif; José, Solange Carvalho Barrios Roveri; Vianello, Rosana Pereira; Pádua, Juliano Gomes; Pappas, Marília de Castro Rodrigues; Gimenes, Marcos Aparecido
Stored RNA plays a key role in seed germination, especially after seeds long-term storage. This study aimed to assess the correlation between germination potential (GP) and RNA integrity in common bean (Phaseolus vulgaris L.) seed accessions stored at -18 °C for 19.25 to 43.75 years and in seeds subjected to artificial aging at high temperature (42 °C) and relative humidity (100%). The GP of long-term preserved and artificially aged seed lots ranged from 3 to 100% and 38–87%, respectively. RNA integrity was evaluated using the RNA Integrity Number (RIN, Agilent Bioanalyzer software). RIN data suggested that: (1) Sample sizes for RIN analysis may need to vary based on the GP of the seeds; (2) RIN has the potential to predict physiological quality, especially in seeds with high GP; (3) RIN values by itself may not accurately reflect the rate of RNA degradation over time, necessitating comparison with a control to determine ΔRIN (the difference between the RIN values of the sample and the control); (4) ΔRIN has a significant positive correlation with GP. These findings highlight the potential of RNA integrity in seeds as a molecular marker for developing tests that complement germination tests.
Post-weaning exposure to cannabidiol disrupts testicular cytoarchitecture and sperm quality in mice
(2025) Carvalho, Renata Karine de; Souza, Maingredy Rodrigues; Nishimura, Akemy Nogueira; Silva, Edvaldo Mendes; Silva, Cinthia R. B.; Guimarães, Francisco Silveira; Andersen, Monica Levy; Saboia-Morais, Simone Maria Teixeira de; Costa, Renata Mazaro e
Cannabidiol (CBD) is a natural cannabinoid with a wide range of potential therapeutic applications, including as an anticonvulsant and for the treatment of inflammatory conditions. It is known that CBD interacts with the endocannabinoid system, which plays a crucial role in various physiological functions. However, its effects on male reproduction have not yet been fully elucidated. Thus, the aim of this study was to evaluate the in vivo effects of CBD on testicular cytoarchitecture and sperm quality in mice. Twenty-one-day old male Swiss mice received intragastric doses of CBD (15 or 30 mg/kg/day) for 34 consecutive days. A control group received sunflower oil. Both doses of CBD reduced the number of Sertoli cells at stages VII–VIII, IX and XII of spermatogenesis. A significant decrease in proliferating cell nuclear antigen (PCNA)-positive spermatocytes at stages VII–VIII was observed in the CBD15 group. In the interstitial compartment of the testis, no significant differences were found in the diameter and volume of Leydig cell nuclei or in the immunostaining of these cells for PCNA in the control and CBD-treated groups. Both doses of CBD reduced the percentage of viable spermatozoa and the percentage of morphologically normal spermatozoa. These findings suggest that daily exposure to CBD may reduce sperm quality, and the mechanisms responsible may be related to perturbations in the endocannabinoid system during spermatogenesis.
Next-generation risk assessment: integrating in vitro data and physiologically-based pharmacokinetic (PBPK) modeling for vancomycin nephrotoxicity evaluation
(2025) Rezende, Francisco da Silva; Pinto, Leonardo Santos Ribeiro; Oliveira, Antonio Anax Falcão de; Paulelli, Ana Carolina Cavalheiro; Costa, Renata Mazaro e; Moraes, Natália Valadares de; Moreira, Fernanda de Lima
Recognizing the need of implementing new approach methodologies (NAMs) in the pharmaceutical industry to establish health-based limits, this study employs an innovative strategy for deriving the permitted daily exposure (PDE) value, using vancomycin as a study case. We integrated in vitro toxicity data with physiologically based pharmacokinetic modeling-facilitated reverse dosimetry (PBPK-RD) to support setting health-based exposure limits, ensuring safety in the context of vancomycin-induced nephrotoxicity. A PBPK model for vancomycin was developed using PK-Sim v.11.3 in both rodents and humans, and its predictive performance was verified by comparing observed and simulated pharmacokinetic profiles. The PBPK-RD approach was then applied to translate in vitro concentration-response data into in vivo dose-response estimates in humans, resulting in a predicted Benchmark Dose Lower Confidence Limit (BMDL5) value of 0.01 mg/kg/day. This value served as the Point of Departure (PoD) for Permitted Daily Exposure (PDE) calculation, corrected for body weight of 50 kg and accounting for uncertainty factors (F). F1 and F2 were set to 1 due to using human data and incorporating interindividual variability within the model, respectively. F3 was set to 10 to address potential chronic exposure effects, while F4 and F5 were each set to 1, reflecting confidence in the dataset and the conservative nature of the PoD. This approach derived a PDE of 0.05 mg/day, lower than the traditionally calculated PDE (0.2 mg/day) based on the lowest clinical dose as the PoD. This study demonstrates the potential of PBPK-RD as a NAM-based strategy for refining toxicological assessments within the pharmaceutical industry.
Effects of exposure to a glyphosate-based herbicide on male mice reproduction
(2025) Rodrigues, Thamyres Cunha; Carvalho, Renata Karine de; Dias Júnior, Walter; Barbosa, Caio Cesar; Andersen, Monica Levy; Costa, Renata Mazaro e
Glyphosate is classified as a post-emergent herbicide with a broad spectrum of activity and is the most widely sold pesticide in Brazil and globally. Glyphosate is also recognized as an endocrine disruptor capable of inducing reproductive disorders in animals. Therefore, this study aimed to evaluate the effects of a glyphosate-based herbicide (Gliz 480 SL) on the reproductive function of male mice during different exposure periods. The following parameters were analyzed: testicular germinal epithelium, daily sperm production, and sperm transit time through the epididymis. A total of 48 adult Swiss mice were divided into three groups exposed to glyphosate at a daily dose of 0.35 mg/kg for 15, 30, or 60 days, and three control groups that received only water (vehicle). A reduction in the relative mass of the caput/corpus of the epididymis, accompanied by a shorter sperm transit time, was observed after 15 days of exposure, resulting in increased sperm accumulation in the cauda epididymis. Stages V–VI of spermatogenesis showed reductions during 15 and 60 days of exposure. Based on the applied protocol, the glyphosate formulation Gliz 480 SL can alter reproductive parameters, particularly during short exposure periods.
Seed-stored transcript integrity as a molecular indicator of viability in conserved common bean germplasm
(2025) Machado, Cristielly de Oliveira Silva; Nunes, Tayara Colins; Costa, Rutiane Moreira de Jesus; Saraiva, Mario Alfredo de Passos; José, Solange Carvalho Barrios Roveri; Salomão, Antonieta Nassif; Pádua, Juliano Gomes; Vianello, Rosana Pereira; Pappas, Marília de Castro Rodrigues; Grynberg, Priscila
Ensuring seed viability over decades is a central challenge in ex situ conservation of plant genetic resources. Standard germination tests, while effective, are destructive and fail to detect early molecular damage that precedes viability loss. RNA integrity has emerged as a promising biomarker due to the inherent vulnerability of mRNA to oxidative degradation in the dry state. In this study, we identified and validated seed-stored mRNAs in common bean (Phaseolus vulgaris), a major crop species extensively represented in global germplasm collections, and investigated transcript degradation patterns in seeds conserved for up to 30 years. Using a comparative genomics approach, we identified 107 P. vulgaris orthologs of long-lived rice mRNAs, many encoding proteins involved in RNA stabilization, oxidoreductase activity, and primary metabolism. Thirty transcripts were validated by RT-qPCR, and the integrity of nine was assessed using paired primers targeting 5′ and 3′ regions. Degradation followed a consistent 5′→3′ pattern, particularly in longer transcripts, and correlated strongly with germination power. Predictive performance varied across transcripts: PSMA4, SMP1, and TRA2 consistently showed strong correlations with viability, whereas others were less informative. The ΔΔCq metric improved resolution by detecting degradation asymmetry. Samples included a genetically diverse panel of conserved, regenerated, and artificially aged accessions, enhancing applicability to real-world genebank conditions. Artificial aging intensified degradation signatures and mirrored patterns observed in naturally aged seeds. Altogether, our results indicate transcript integrity as a molecular biomarker for seed viability, supporting the development of robust molecular tools to inform decision-making and regeneration planning in long-term germplasm conservation.
Effects of exposure to the fungicide mancozeb on reproductive and somatic parameters of male mice
(2025) Rodrigues, Thamyres Cunha; Carvalho, Renata Karine de; Dias Júnior, Walter; Barbosa, Caio Cesar; Andersen, Monica Levy; Costa, Renata Mazaro e
Mancozeb (MZB) is a pesticide that is used widely against a range of fungal diseases in plants. However, its effects on the male reproductive system are still unclear. Thus, this study analyzed the effects of MZB on the reproductive system of mice over different exposure periods. In addition, somatic parameters were evaluated. For this purpose, adult male Swiss mice were distributed into 6 groups (n = 8 animals/group): 3 groups orally treated with 0.37 mg.kg-1 of MZB for 15, 30, or 60 days, and 3 control groups receiving only the vehicle (water) for the same period. The results showed an increase in the glycemic index (p < 0.05), while the gastrocnemius muscle mass was lower in mice exposed to MZB (p < 0.05). The seminal vesicle of treated mice was increased (p < 0.05). MZB also promoted changes in the frequency of spermatogenic stages and in the number of Sertoli cells (p < 0.05). Moreover, epididymal sperm count was increased in the cauda segment of mice exposed to MZB (p < 0.05). These findings may be the result of a direct action of MZB on the thyroid pathway, which has been recognized as a target of MZB metabolites, besides being an important pathway involved in the male reproduction. However, further research is warranted to confirm this hypothesis.
Exploring the genetic diversity of common bean germplasm: insights into Andean gene pool variability
(2025) Silva, Cecilia Luvizutti Ferreira da; Grattapaglia, Dario; Valdisser, Paula Arielle Mendes Ribeiro; Torga, Paula Pereira; Rangel, Alessandra da Cunha Moraes; Brondani, Claudio; Coelho, Alexandre Siqueira Guedes; Borba, Tereza Cristina de Oliveira; Vianello, Rosana Pereira
Common bean (Phaseolus vulgaris) is among the most widely consumed legumes globally, with Brazil playing a crucial role in preserving and expanding its existing genetic diversity. This study aimed to characterize a subset of 863 common bean accessions from Brazil's Gene Banks, mainly of Andean origin. A germplasm collection was genotyped with 4275 SNPs using the EMBRAPA Multispecies 65KChip. Population structure analysis revealed two main groups: Andean (n = 558) and Middle American (n = 267), along with 38 admixed accessions. Andean group exhibited lower gene diversity (GD = 0.086), and allelic richness (AR = 1.83) compared to the Middle American group (GD = 0.270, AR = 1.98). Brazilian landraces in the Andean and Middle American groups showed potentially lower overall diversity, emphasizing the need for conservation efforts to preserve these genetic resources. The Andean Brazilian core collection (n = 221; GD = 0.095) encompasses the active collection diversity evaluated (n = 337; GD = 0.093). A total of 26 SNPs potentially under selection, mainly associated with plant development and defense, were identified. Georeferencing landraces using climate maps identified potentially valuable varieties adapted to drought (e.g., BGF0011779, BGF0012528, BGF0013826) and high temperatures and low-fertility soils (e.g., BGF0016128, BGF0013871), highlighting their relevance for conservation and sustainable use in breeding programs. Accessions' photographs showcased a wide range of morphological diversity, colors, types, shapes, and sizes of beans. Our findings reveal a significant genetic diversity among common bean germplasm, offering practical breeding opportunities and enhancing the value of gene bank collections. Certain landraces show potential for adapting to challenging climatic conditions, making them promising subjects for further adaptation studies.
Maternal age precursors during lactation alters offspring glycemic homeostasis early in life
(2025) Saavedra, Lucas Paulo Jacinto; Francisco, Flávio Andrade; Raposo, Scarlett Rodrigues; Cavalcante, Keilah Valéria Naves; Buttow, Nilza Cristina; Borges, Stephanie Carvalho; Gomes, Rodrigo Mello; Campos, Hericles Mesquita; Gonçalves, Gessica Dutra; Piovan, Silvano; Ghedini, Paulo César
Background: Advanced glycation end-products (AGEs) are linked to the development of oxidative stress, insulin resistance, and impaired insulin secretion. Adverse early life conditions, such as exposure to AGEs and their precursors, may lead offspring to the development of metabolic dysfunction in adulthood. Nonetheless, the early impact in offspring metabolism by maternal intake of AGEs precursors during lactation is not known. Objective: Investigate early life metabolism of the offspring whose breastfeeding dams were orally exposed to AGEs precursor. Methods: Breastfeeding Wistar rats were daily treated with the glycation precursor methylglyoxal (MG—60 mg/kg of bodyweight) by gavage or saline 0.9% control (CO) until weaning. In vivo glycemic homeostasis in male offspring was assessed, followed by euthanasia for tissue sample collection for ex vivo assessments. Results: At weaning, MG offspring presented decreased bodyweight (p < 0.05), perigonadal (p < 0.01) and retroperitoneal (p < 0.01) fat. MG offspring presented decreased glucose tolerance (p < 0.05), lower basal insulinemia (p < 0.001), reduced high-glucose static insulin secretion (p < 0.05), and reduced pancreatic islet area (p < 0.05). Accordingly, MG offspring pancreas showed lower GSH and SOD activity (p < 0.05; p < 0.001, respectively) and increased MPO (p < 0.05) activity. Conclusions: The consumption of AGE precursors by breastfeeding dams impaired offspring pancreatic function and glycemic homeostasis early in life.
Evaluation of the neuroprotective potential of benzylidene digoxin 15 against oxidative stress in a neuroinflammation models induced by lipopolysaccharide and on neuronal differentiation of hippocampal neural precursor cells
(2025) Cordeiro, Gilvânia Aparecida Rabelo; Faria, Jéssica Alves; Anjos, Letícia Pavan dos; Garcia, Israel Jose Pereira; Neves, Eduarda P. F. I.; Lima, Gustavo Fernando de Frazão; Campos, Hericles Mesquita; Ferreira, Pâmela Yasmin de Oliveira; Ghedini, Paulo César; Kawamoto, Elisa Mitiko
Neuroinflammation, often driven by the overproduction of reactive oxygen species (ROS), plays a crucial role in the pathogenesis of neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases. The susceptibility of the brain to oxidative stress is attributed to its high metabolic activity and limited antioxidant defense. This study aimed to evaluate the neuroprotective potential of Benzylidene Digoxin 15 (BD-15) following treatment and pretreatment in a lipopolysaccharide (LPS)-induced neuroinflammation model. Additionally, we examined whether BD-15 enhances the generation of neurons from neural progenitor cells (NPCs).Male Wistar rats were used for acute treatment studies and divided into four groups: control (saline), BD-15 (100 μg/kg), LPS (250 μg/kg), and LPS + BD-15 (250 μg/kg + 100 μg/kg). Swiss albino mice were used for chronic pretreatment studies and divided into the following groups: control (saline), BD-15 (0.56 mg/kg), LPS (1 mg/kg), and LPS + BD-15 (1 mg/kg + 0.56 mg/kg). Behavioral changes were assessed using the open field test, and brain tissues were analyzed for oxidative stress markers, including malondialdehyde (MDA), reduced glutathione (GSH), protein carbonylation, catalase (CAT), superoxide dismutase (SOD), and glutathione S-transferase (GST). To assess neurogenesis, primary NPC cultures derived from the hippocampus of newborn Wistar rats were used, which led to reduced locomotor activity and increased oxidative stress, particularly in the cortex, as indicated by elevated MDA levels and reduced GSH levels. BD-15 treatment reversed these effects, notably by restoring GSH levels and reducing protein carbonylation in the cerebellum. Chronic BD-15 treatment in Swiss mice improved oxidative stress markers including MDA, SOD, CAT, and GST. Furthermore, BD-15 exhibits neuroprotective properties by alleviating oxidative stress and motor dysfunction, suggesting its potential as a therapeutic agent for neuroinflammatory disorders. However, BD-15 did not affect NPC cell proliferation, indicating that this cardiotonic steroid did not alter the cell cycle of these progenitor cells.
Neurobiology of L-proline: from molecules to behavior
(2025) Carvalho, Gustavo Almeida de; Cavalcante, Daniel Pereira; Parreira, Ricardo Cambraia; Chiareli, Raphaela Almeida; Leoncini, Giovanni Ortiz; Gomez, Renato Santiago; Ulrich, Alexander Henning; Caixeta, Leonardo Ferreira; Oliveira-Lima, Onésia Cristina de; Pinto, Mauro Cunha Xavier
L-proline is an amino acid with a unique cyclic structure, involvement in various physiological processes, such as protein synthesis, collagen production, and neurotransmission. This review explores the complex roles of proline in the central nervous system (CNS), where it contributes to both excitatory and inhibitory neurotransmission. Additionally, L-proline has distinct metabolic functions attributed to its structural properties. The concentration-dependent effects of L-proline indicate its importance in CNS function, with potential implications for health and disease. Studies in animal models suggest that L-proline influences cognitive function and behavior, with dysregulated levels linked to learning and memory deficits. Furthermore, this review addresses the neuropathological consequences of hyperprolinemia, a metabolic disorder marked by elevated L-proline levels in the CNS and examines the potential role of L-proline in neurological and psychiatric disorders. In sum, this work provides a comprehensive perspective on the neurobiological importance of L-proline, underscoring its involvement in neurotransmission, behavioral modulation, and disease pathology.
GlyT1 inhibition promotes post-ischemic neuroprotection in the MCAO model
(2025) Cavalcante, Daniel Pereira; Santos, Antonio Ítalo dos; Carvalho, Gustavo Almeida de; Gomez, Renato Santiago; Assunção, Leandro do Prado; Bailão, Alexandre Melo; Pinto, Mauro Cunha Xavier
Glycine transporter type 1 (GlyT1) regulates extracellular glycine levels and modulates N-methyl-D-aspartate receptor (NMDAR) activity, positioning it as a promising target in excitotoxic and ischemic conditions. While previous studies have shown that GlyT1 inhibition prior to injury confers neuroprotection, its therapeutic potential in a post-ischemic context remains unclear. Here, we investigated the neuroprotective effects of NFPS, a selective GlyT1 inhibitor, administered after the induction of permanent middle cerebral artery occlusion (MCAO) in mice. NFPS (1.25, 2.5, or 5.0 mg/kg, i.p.) was administered once daily for three days, beginning 24 h post-ischemia. NFPS treatment significantly reduced infarct volume and improved motor function in a dose-dependent manner. Additionally, NFPS reduced reactive oxygen species, nitric oxide, and lipid peroxidation, alongside adjustments in antioxidant enzymes and glutathione-related activity. Proteomic analysis of cortical tissue from healthy mice treated with NFPS revealed enrichment of pathways related to glutamatergic synapse, Parkinson disease, and dopaminergic synapse pathways, suggesting modulation of synaptic plasticity and metabolic resilience. Western blot analysis confirmed an increase in GluN2A and a decrease in GluN2B expression, consistent with a shift toward prosurvival NMDAR signaling. Collectively, these findings demonstrate that post-ischemic GlyT1 inhibition with NFPS confers robust neuroprotection through coordinated regulation of excitotoxicity and oxidative stress, supporting its potential as a therapeutic strategy for ischemic stroke.
GlyT1 inhibition promotes neuroprotection in the middle cerebral artery occlusion model through the activation of GluN2A-containing NMDAR
(2025) Cavalcante, Daniel Pereira; Nunes, Antonio Ítalo dos Santos; Silva, Eduardo Rosa da; Carvalho, Gustavo Almeida de; Chiareli, Raphaela Almeida; Oliveira-Lima, Onésia Cristina de; Leoncini, Giovanni Ortiz; Ulrich, Alexander Henning; Gomez, Renato Santiago Gomez; Pinto, Mauro Cunha Xavier
Glycine Transporter Type 1 (GlyT1) inhibition confers neuroprotection against different forms of cerebral damage. This effect occurs through the elevation of synaptic glycine concentrations, which enhances N-methyl-d-aspartate receptor (NMDAR) activation by glutamate. To investigate the neuroprotective mechanism of GlyT1 inhibition, we used the Middle Cerebral Artery Occlusion (MCAO) model in male C57BL/6 mice, aged 10–12 weeks. We administered N-[3-(4′-fluorophenyl)-3-(4′-phenylphenoxy)propyl] sarcosine (NFPS), a GlyT1 inhibitor, 24 h prior to ischemia induction. NFPS pretreatment provided significant neuroprotection in the MCAO model, associated with modulation of pathways related to long-term potentiation. Specifically, GluN2A subunit expression was upregulated, while GluN2B subunit expression was downregulated in cortical areas, correlating with enhanced phosphorylation of CaMKIV and CREB proteins. Coadministration with the GluN2B antagonist Eliprodil or the CREB inhibitor C646 did not affect the neuroprotective effects of NFPS pretreatment, but TCN-201, a specific GluN2A antagonist, disrupted these effects. These findings suggest that GlyT1 inhibition mediates neuroprotection through activation of GluN2A-containing NMDARs and the GluN2A/CaMKIV/CREB signaling cascade, thereby modulating the balance between GluN2A and GluN2B subunits.
Screening of fluopyram-based formulation toxicity in non-target organisms
(2025) Cotrim, Carlos Filipe Camilo; Silva, Lucas Leonardo da; Silva, Natanael Alves da; Lima, Gabriela Gomes; Melo Bisneto, Abel Vieira de; Lee, Chen Chen; Damin, Virgínia; Almeida, Luciane Madureira de
luopyram is a fungicide with nematicidal properties widely used in agriculture, found in commercial products for agricultural pest management. Despite its increasing agricultural use, limited information exists on its cytogenotoxic and plant-level impacts. This study evaluated the cytogenotoxic and ecotoxicological effects of a fluopyram-based formulation on non-target organisms, including Salmonella typhimurium (TA98 and TA100 strains), Artemia salina, and seeds of Lactuca sativa (lettuce), Allium cepa (onion), and Cucumis sativus (cucumber). Concentrations ranging from 0.017 to 5.00 mg mL−1 were tested. The pesticide did not induce mutagenic responses in the Salmonella strains tested but demonstrated cytotoxicity at high concentrations (≥1.67 mg mL−1). In A. salina, increasing mortality was observed from 0.210 mg mL−1, with an estimated LC50 of 1.021 mg mL−1. Regarding germination, onion seeds were affected at the highest tested concentration, while root growth in plant species exhibited a hormetic response, with stimulation at low concentrations and inhibition at higher ones. These findings underscore the need for continued environmental monitoring and risk assessment of fluopyram-based formulations, particularly regarding aquatic and plant ecosystems.
Dioclea violacea lectin exerts pro-angiogenic effects by increasing VEGF and TNF-α levels via carbohydrate recognition domain
(2025) Melo Bisneto, Abel Vieira de; Paiva, Felipe Eduardo Alves de; Fernandes, Amanda Silva; Roma, Renato Rodrigues; Silva, Luana Santos; Chiesi, Giovana Valsani; Franchi, Leonardo Pereira; Cardoso, Cléver Gomes; Teixeira, Claudener Souza; Lee, Chen Chen
Due to their interesting biological activities, a mannose-binding lectin isolated from Dioclea violacea seeds, known as DvL have attracted considerable attention. In this study, we performed macroscopic, histologic, and immunohistochemical analysis on chicken embryo chorioallantoic membranes (CAM) to investigate the effects of DvL on the angiogenic process. Data showed a potential angiogenic effect of DvL at the highest concentrations tested (50 and 100 μg/mL). This effect was confirmed through increased neovascularization, inflammatory cells, and fibroblasts in histological analysis of the CAM. In addition, the immunohistochemistry of CAM showed that DvL induced secretion of TNF-α and VEGF, important cytokines involved in angiogenesis. Therefore, increased neovascularization may result from a pro-inflammatory response through VEGF and TNF-α secretion. In contrast, the DvL effects on the angiogenic process and the TNF-α and VEGF secretion were significantly reduced by co-incubation with mannose. Thus, protein-carbohydrate interactions between DvL and cell membrane glycans are likely the main events involved in this effect. Therefore, our results demonstrated that DvL is a potent angiogenic agent, suggesting its potential application as a prototype molecule for developing new drugs with healing properties.
Lectin from vatairea macrocarpa (benth.) Ducke exhibits selective cytotoxicity and angiogenesis inhibition in lung cancer cells
(2025) Costa, Adrielle Rodrigues; Roma, Renato Rodrigues; Melo Bisneto, Abel Vieira de; Paiva, Felipe Eduardo Alves de; Véras, Jefferson Hollanda; Curcio, Juliana Santana de; Silva, Lívia do Carmo; Lee, Chen Chen; Cardoso, Cléver Gomes; Lacerda, Elisângela de Paula Silveira; Teixeira, Claudener Souza
Angiogenesis plays a vital role in tumor development, and its inhibition, along with selective cytotoxicity, represents a promising strategy for cancer treatment. Lectins, carbohydrate-binding proteins, have demonstrated dual potential in blocking angiogenesis and selectively targeting tumor cells. This study investigates the antiangiogenic and cytotoxic properties of Vatairea macrocarpa lectin (VML) through the chorioallantoic membrane (CAM) assay and tests on normal VERO cells and tumor cell lines A549, SH-SY5Y, S180, and B16-F10. VML exhibited selective cytotoxicity exclusively against A549 lung carcinoma cells, with an IC50 of 97.21 μg/mL, showing no significant toxicity to other lines. In the CAM assay, VML significantly inhibited neovascularization triggered by A549 cells, reaching 70.38% inhibition at 100 μg/mL. Immunohistochemical analyses confirmed the suppression of angiogenesis by showing decreased expression of VEGF and TGF-β. Histological assessments also revealed reductions in new vessel formation, inflammatory cell infiltration, fibroblast presence, and membrane thickening. These results highlight VML’s dual role in inhibiting angiogenesis and exerting selective cytotoxicity, likely due to its specific interaction with tumor-associated carbohydrates. Consequently, VML emerges as a potential candidate for targeted cancer therapy or as a complementary therapeutic agent. Further research is necessary to fully understand the molecular mechanisms underlying its antitumor activity.
Development of alginate/carboxymethylcellulose films incorporated with Canavalia ensiformis Lectin (ConA) with angiogenic properties
(2025) Santos, Maria Helena Cruz dos; Santos, Ana Lúcia Estevam dos; Santos, Israel J. M.; Roma, Renato Rodrigues; Melo Bisneto, Abel Vieira de; Cardoso, Cléver Gomes; Rocha, Bruno Anderson Matias da; Lee, Chen Chen ; Souza, Aryane Tofanello de; Silva, Wanius José Garcia da
The development of new materials for wound care is a critical area, focused on creating dressings with improved properties, such as high absorption, flexibility, and low cost. In this context, natural polymers such as alginate and carboxymethyl cellulose (CMC) emerge as promising choices, given their biodegradability and their ability to promote an ideal healing environment. Concomitantly, lectins with angiogenic potential have been extensively investigated for their ability to modulate cellular responses and induce the formation of new blood vessels. This research aims to incorporate the lectin from Canavalia ensiformis (ConA) into alginate and carboxymethylcellulose (CMC) films to promote blood vessel growth and induce revascularization as a therapeutic approach. Film characterization and physicochemical tests showed efficient lectin/film incorporation, as observed through differential scanning calorimetry (DSC) analysis and Fourier-transform infrared spectroscopy (FTIR). DSC analysis showed that alginate/CMC films with ConA tend to retain less water, volatilizing more easily, with a temperature difference of 94 and 81 °C to 69 and 77 °C films containing ConA. In addition to the significantly prolonged retention capacity of ConA in the film, FTIR data suggest that ConA is anchored in the alginate matrix due to the cross-linked nature of the film chain, with minimal chemical interactions (or chemical bonds). Analysis of hemagglutinating activity and immunohistochemical assays showed an increase in the expression of the angiogenic factors TGF-β and VEGF. These results indicate that the biopolymers used are an effective alternative for wound treatment, pointing to future research into the development of therapeutic biofilms.
Exploring the clinical utility of cardiorespiratory optimal point in heart failure patients: creating a new research gap
(2025) Silva, Weder Alves da; Sá Filho, Alberto Souza de; Ramos, Plínio dos Santos; Chiappa, Adriana Meira Güntzel; Fernandes, Vicente Aprigliano; Silva, Iransé Oliveira; Cunha, Raphael Martins da; Fajemiroye, James Oluwagbamigbe; Vieira, Rodolfo de Paula; Ferrari, Gerson Luis de Moraes; Chiappa, Gaspar Rogério da Silva
The cardiorespiratory optimal point (COP) is an emerging submaximal parameter from cardiopulmonary exercise testing (CPET) that reflects the optimal balance between cardiac workload and pulmonary ventilation. Recent studies have explored the clinical utility and prognostic value of the COP in various populations, particularly in patients with heart failure (HF). This comprehensive literature review evaluated the current evidence on the COP and its potential as an independent risk factor for cardiovascular disease and mortality. The COP has been identified as a predictor of all-cause and cardiovascular mortality, with elevated values being significantly associated with an increased risk. Studies have demonstrated that higher COP values correlate with greater mortality risk independent of traditional risk factors, with significant sex-based differences. Evidence suggests that COP values greater than 26 significantly influence mortality rates and lead to a worse prognosis in patients with HF. For example, individuals with a COP > 30 had an approximately six-fold higher mortality risk (17.1%) than those with a COP < 22, and the combination of a high COP (>30) + low VO2max leads to a significant increase in the risks of adverse effects (30.9%). This underscores the importance of the COP in the clinical management and risk stratification of HF patients. While the COP shows promise as a valuable submaximal marker with significant prognostic implications, further research is needed to establish its superiority over other established prognostic markers and elucidate the underlying mechanisms linking the COP to health outcomes. Nonetheless, the ability of the COP to predict mortality and enhance risk stratification in diverse populations makes it a promising tool in clinical practice.
Bridging emotional and intellectual dimensions in translational neuroscience
(2025) Fajemiroye, James Oluwagbamigbe
Characterization of a novel small chemical entity with anxiolytic- and antidepressant-like effects targeting multiple receptors
(2025) Ogbu, John Ihayi; Moreira, Caroline Vitória de Lima; Pereira, Jhon Kennedy Alves; Silva, Kariny P. da; Lião, Luciano Morais; Dietz, Gunnar P. H.; Silva, Mirely Vitória Farias da; Sá Filho, Alberto Souza de; Silva Júnior, Edeildo Ferreira da; Pedrino, Gustavo Rodrigues; Fajemiroy, James Oluwagbamigbe
Effective restoration of mental health in psychiatric disorders increasingly hinges on bridging neurobiological insights with clinically validated pharmacotherapies. The etiological heterogeneity of anxiety and depression underscores the need for novel compounds capable of modulating multiple neurochemical systems. In this study, we describe the synthesis and detailed characterization of a hydroxyl phenethyl acetamide analog (LQFM334) designed to target key receptors involved in mood regulation. LQFM334 exhibited a favorable safety profile and elicited robust anxiolytic- and antidepressant-like effects in mouse models. These behavioral outcomes were supported by in silico receptor profiling and in vitro functional assays, identifying LQFM334 as a potential agonist at serotonergic (5-HT1A/5-HT2A) and melatonergic (MT1/MT2) receptors. Pharmacological blockades of these receptors, but not of α-adrenergic or dopaminergic receptors, attenuated its behavioral effects. These findings position LQFM334 as a promising multireceptor ligand exemplifying a polypharmacology approach for the treatment of complex psychiatric conditions. The dual serotonergic and melatonergic mechanisms confer strong translational relevance involving the modulation of mood, stress resilience, and circadian rhythms domains that are frequently disrupted in affective disorders. These findings support LQFM334's potential in delivering broad-spectrum and clinically relevant psychiatric symptom relief.

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