Carbon dots (CDs) are emerging nanomaterials with tunable optical properties and promising scalability; however, their potential toxicity remains a key concern for biomedical and environmental applications. In this study, we investigated the in vitro and in vivo toxicity of CDs synthesized from spent coffee grounds (SCG-CD) via pyrolysis. Thermogravimetric analysis (TGA) was used to determine the optimal synthesis parameters, while fluorescence spectroscopy was used to confirm CD formation and excitation-dependent emission. The Design of Experiments (DoE) approach identified conditions yielding blue-emissive CDs with a maximum photoluminescence quantum yield of 6% (400 °C, 3 h, named S4_SCG-CD). Fluorescence analysis revealed pH-dependent emission enhancement under alkaline conditions. Structural characterization by Fourier-transform infrared spectroscopy and X-ray diffraction demonstrated surface functionalization and a semicrystalline framework. In vitro MTT assays indicated no cytotoxicity across tested concentrations, and in vivo assays in mice and zebrafish embryos revealed no acute toxicity. The S4_SCG-CD sample was classified as Category 5 (LD50 ≥ 5000 mg/kg) under the Globally Harmonized System and "practically nontoxic" (LC50 > 150 μg/mL) according to the Fish and Wildlife Service. These findings highlight spent coffee grounds as a sustainable precursor for generating biocompatible, low-toxicity materials with potential applications in bioimaging and eco-friendly nanotechnology.

The Celtis iguanaea (Jacq.) Sarg., Cannabaceae, standardized spray-dried extract, underwent acute safety evaluation using a range of alternative toxicological models in alignment with Organization for Economic Co-operation and Development Test Guidelines. Acute aquatic toxicity was assessed using the Artemia salina lethality test (LC50 418.4 μg/ml) and the zebrafish (Danio rerio) embryo toxicity test (OECD TG 236; LC50 1116.0 μg/ml). According to the Globally Harmonized System aquatic toxicity categories, C. iguanaea spray-dried extract is classified as non-hazardous (LC50 > 100 μg/ml). In vitro assays included cytotoxicity (methyl thiazolyl tetrazolium assay –in WI-38 and HaCaT cells; resazurin in Caco-2 and HT-29 cells), cell adhesion genotoxicity (comet assay; OECD TG 489), and mutagenicity (cytokinesis-block micronucleus assay; OECD TG 487). Celtis iguanaea spray-dried extract showed no cytotoxic, genotoxic, or mutagenic effects up to 250 μg/ml and enhanced HaCaT cell viability and adhesion at higher concentrations (100 μg/ml), suggesting potential support for wound healing. No antimicrobial activity was observed against Candida spp., ESKAPE pathogens, or bacteria associated with urinary tract infections (MIC > 1024.0 μg/ml). This weight-of-evidence assessment supports the safe use of C. iguanaea spray-dried extract in topical or oral formulations and provides data suitable for regulatory hazard characterization and acute risk assessment.

Ivermectin, a macrocyclic lactone used in veterinary medicine and aquaculture, can pose risks to non-target aquatic organisms. Although its developmental toxicity in fish is well documented, mitigation strategies remain poorly explored, and the protective potential of commercial green propolis has not been investigated. This study evaluated whether a commercial aqueous extract of green propolis mitigates ivermectin embryotoxicity in zebrafish (Danio rerio). Embryos were exposed to ivermectin or green propolis (100, 200, 400, and 800 µg.L-1) from 6 to 120 h post-fertilization. For co-exposure, the lowest ivermectin concentration that caused significant mortality (200 µg.L-1; 35% mortality, p = 0.02) was combined with 200 µg.L-1 of green propolis. Mortality, hatching rate, heart rate, length, and malformations were assessed. Ivermectin induced concentration-dependent toxicity, with mortality reaching 55% at 400 µg.L-1 (p < 0.001) and 73% at 800 µg.L-1 (p < 0.001), alongside impaired hatching, increased heart rate, and growth retardation. Green propolis alone resulted in mortality rates below 22% across all tested concentrations. Co-exposure significantly reduced mortality from 35% to 5% (χ² = 16.88, p = 3.99 × 10-5), yielding a 30% absolute and 85.7% relative risk reduction. Co-exposure also improved hatching rate, did not differ significantly from control levels in heart rate, and increased larval length compared to ivermectin alone. However, propolis failed to prevent morphological abnormalities, including yolk sac and pericardial edemas, tail curvature, and craniofacial defects. In conclusion, commercial green propolis effectively mitigates ivermectin-induced functional toxicity in zebrafish embryos but is insufficient to prevent structural malformations.

Head and neck cancer (HNC) remains a major therapeutic challenge due to its biological heterogeneity and limited response to current treatments, highlighting the need for more effective and less toxic therapeutic strategies. Annona coriacea Mart., a plant native to the Brazilian Cerrado, is a source of bioactive acetogenins. In this study, we evaluated the antitumor effects of acetogenin-enriched fractions from A. coriacea using in vitro and in vivo models of HNC. The fractions exhibited cytotoxic activity against FaDu and HN13 cells, with IC50 values ranging from 2.42 to 8.25 μg/mL and from 1.61 to 12.57 μg/mL, respectively, while showing lower toxicity toward nontumor cells. Mechanistic analyses suggested the involvement of mitochondrial-associated apoptotic-like and necroptotic cell death processes. Molecular docking analyses indicated a possible modulatory interaction between acetogenins and tumor necrosis factor receptor 1 (TNFR1). In vivo, the selected fraction ACL3 reduced tumor growth and angiogenesis in the CAM model without inducing vascular irritation, as confirmed by the HET-CAM assay. Together, these findings demonstrate that A. coriacea acetogenin-rich fractions exhibit selective antitumor activity, induce mitochondrial-mediated and necroptosis-related cell death mechanisms, and inhibit tumor-associated angiogenesis, supporting their potential as promising candidates for further preclinical investigation in HNC.

A series of second-generation compounds analogous to Santacruzamate A were designed, synthesized, and evaluated for their selective cytotoxic activity against the breast cancer cell line MDA-MB-231 (ATCC HTB-26). Compound 7 demonstrated the highest cytotoxicity and selectivity among the tested compounds, with an IC50 value of 8.30 μM, comparable to those of the positive controls cisplatin (8.46 μM) and etoposide (12 μM). In silico studies identified histone deacetylase 8 (HDAC8) as a potential target of compound 7, supporting its role as an HDAC inhibitor. Experimental data further confirmed the pro-apoptotic activity of compound 7, as it significantly increased caspase-3 and caspase-9 activities, along with TP53 and BAK expression compared to the untreated group. These findings indicate that compound 7 induces apoptotic cell death in tumor cells through the intrinsic mitochondrial pathway. This study highlights compound 7 as a promising candidate for further exploration as a selective anticancer agent targeting breast cancer cells.

Intoxication is a serious public health problem worldwide and in the case of heavy metal intoxication, the presence and increase of these elements in the environment can be an aggravating factor, for example, after the collapse of mining dams. In this context, the objective of this study was to analyze the epidemiological profile of heavy metal intoxication before and after the rupture of the Fundão and Mina Córrego do Feijão dams in the state of Minas Gerais, Brazil, and to verify a possible relation of increase in cases after the disasters. Data were collected through the Notifiable Diseases Information System (SINAN) in the period before (2010-2015) (2016-2018) and after (2016-2021) (2019-2021) the rupture of the Fundão and Mina Córrego dams of beans, respectively. After the disasters, there was an increase in cases of heavy metal intoxication both nationally (5.3% - Fundão and 23.3% - Córrego do Feijão mine) and in the state of Minas Gerais (34.7% - Fundão and 34 .3% - Mina Córrego do Feijão) related to different circumstances, but progressing to cure without sequelae in most cases. Although it is not possible to directly correlate disasters with the increase in the number of people intoxicated by metals, this work raises questions about the transfer of these events in the increase in cases of intoxication, requiring further studies on the subject.

This systematic review aims to examine the existing literature on the therapeutic potential of medicinal plants to improve caudal fin regeneration and wound healing in zebrafish (Danio rerio), focusing on uncovering their pharmacological properties and potential use in enhancing tissue repair and regeneration. A thorough review of suitable and eligible full-text articles was performed on PubMed, Scopus, Web of Science, and Google Scholar from 1 st January 2014 to 31 st December 2024. These articles were searched using the Medical Subject Headings terms “zebrafish,” “zebrafish larvae,” “zebrafish embryo,” “angiogenesis,” “Medicinal plants,” “Natural products,” “Fin regeneration,” “wound healing,” and “inflammation.” Here, 520 articles on medicinal plants and their potential in caudal fin regeneration and wound healing in zebrafish were identified across the databases searched, of which 26 were included in this study following screening. After thoroughly reviewing the articles, some were found to have used multiple medicinal plants. Thus, 38 medicinal plants were found to have promoted effects on zebrafish caudal fin regeneration and wound healing, and 21 revealed no effects on either caudal fin regeneration and wound healing. This systematic review explores the therapeutic potential of medicinal plants in caudal fin regeneration and wound healing in a zebrafish model. The results show a promising effect of various plant species in enhancing fin regeneration and wound healing. Further research is needed to understand the molecular mechanisms and to translate these findings into clinical applications for human wound healing and regenerative medicine.

Fish may have different sensitivity to pollutants present in the water. We analyzed the liver histology, and P-gp expression in six species of fish from the Doce River basin. Fish were caught at six different points in the Doce River, and liver samples were taken for histological analysis. P-gp expression was analyzed using an immunohistochemical technique. In Astyanax lacustris, Hoplias intermedius, Hypostomus affinis, Trachelyopterus striatulus and Oligosarcus acutirostris, a double arrangement of hepatocyte plates was generally observed (tubular-form), while in Deutorodon taeniatus, a single arrangement of hepatocyte plates was frequently observed (cord-like). Histological changes, such as cytoplasmic vacuolation and nuclear alteration, were observed in the livers of all species analyzed, however, the species A. lacustris (34.1%) and H. affinis (33.3%) were those with the fewest individuals with histological changes. The H. intermedius, T. striatulus, and O. acutirostris were the species that presented more than 80% of their individuals with histological changes. The A. lacustris and H. affinis were the species that showed the highest P-pg immunolabeling in the liver, while the T. striatulus and O. acutirostris had the lowest levels. These results support the hypothesis that levels of P-gp expression could respond to the resistance or sensitivity of each species to environmental pollutants.

We describe the toxicity of multiwalled carbon nanotubes (MWCNTs) in two aquatic species: Danio rerio and Artemia salina. Fish were exposed to 25 mg L-1, 50 mg L-1, and 100 mg L-1 MWCNTs for 7 days. After exposure, the gills from D. rerio showed lamellar fusion and epithelial lifting in the secondary lamellae, and vasodilation in the primary lamellae. In the gills, heat shock protein 70 and Bax (pro apoptotic member) were stained more intensely in the treated groups than in the control group. The nauplii of A. salina were exposed to 25 mu g L-1, 50 mu g L-1, and 100 mu g L-1 MWCNTs for 96 h. After exposure, the nauplii from the control group presented 20 % mortality, whereas the 25 mu g mL-1, 50 mu g mL-1, and 100 mu g L-1 groups had 46.7 %, 70 %, and 100 % mortality, respectively. The nauplii exposed to 25 mu g mL1 and 50 mu g mL1 MWCNTs had black aggregates in the intestine because of the uptake of nanomaterials. In addition, the 25 mu g mL-1 and 50 mu g mL- 1 MWCNT groups had black aggregates attached onto the body surface, appendages of the second pair, and mandibles.The results revealed the toxic effects of MWCNTs on the two aquatic organisms, and both species showed great potential for toxicological evaluation of MWCNTs in aquatic environments.

OBJECTIVE:Breast cancer represents the most prevalent type of tumor throughout the world. Considering the side effects caused by the available treatments, the resistance acquired by cells to cytotoxic agents, and metastasis, it is necessary to search for new sources of antitumor and antimetastatic therapies. Given the numerous antitumor studies involving the synthesis of substances derived from the naphthoquinone lapachol, we investigated the antineoplastic potential of a new synthetic substance (APO-3) derived from lapachol, alone and in combination with the chemotherapeutic agent paclitaxel (PTX), against 4T1 cells, a murine breast cancer cell line. METHODS/RESULTS:In MTT assay APO-3 and the APO-3/PTX combination were selectively cytotoxic to 4T1 cells, with APO-3/PTX being approximately 6.5 and 15 times more selective than PTX and APO-3, respectively. After zymography, APO-3/PTX was more effective in decreasing matrix metalloproteinase-9 (MMP-9) activity compared with APO-3 alone. In the clonogenic assay, APO-3/PTX reduced the number of colonies more effectively than APO-3 or PTX alone. APO-3/PTX also inhibited cell migration, as did PTX and APO-3 alone. The combination increased the expression of proteins involved in the intrinsic apoptotic pathway and induced cellular morphological changes characteristic of this type of cell death, acting similarly to PTX alone. APO-3 increased Receptor-interacting serine/threonine-protein kinase 1 (RIP1) and caused morphological changes characteristic of apoptosis and necroptosis in 4T1 cells. CONCLUSION:Taken together, APO-3 presented antitumor action against 4T1 cells, but the APO-3/PTX combination was more effective than either substance alone.

Glioblastoma is the most frequent primary malignant brain tumor without effective treatment, which makes this work extremely relevant. The study of the bioactive compounds from medicinal plants plays an important role in the discovery of new drugs.This research investigated the constituents of Tapirira guianensis and its antitumor potential ( in vitro and in vivo) in glioblastoma. The T. guianensis extracts were characterized by mass spectrometry. The ethyl acetate partition (01ID) and its fractions 01ID-F2 and 01ID-F4 from T. guianensis showed potential antitumor treatment evidenced by selective cytotoxicity for GAMG with IC50 14.1 mu g/mL, 83.07 mu g/mL, 59.27 mu g/mL and U251 with IC50 25.92 mu g/mL, 37.3 mu g/mL and 18.84 mu g/mL. Fractions 01ID-F2 and 01ID-F4 were 10 times more selective when compared to TMZ and 01ID for the two evaluated cell lines. T. guianensis also reduced matrix metalloproteinases 2 - 01ID-F2 (21.84%), 01ID-F4 (29.6%) and 9 - 01ID-F4 (73.42%), ID-F4 (53.84%) activities, and induced apoptosis mainly through the extrinsic pathway. Furthermore, all treatments significantly reduced tumor size (01ID p < 0,01, 01ID-F2 p < 0,01 and 01ID-F4 p < 0,0001) and caused blood vessels to shrink in vivo . The present findings highlight that T. guianensis exhibits considerable antitumor potential in preclinical studies of glioblastoma. This ability may be related to the phenolic compounds and sesquiterpene derivatives identified in the extracts. This study deserves further in vivo research, followed by clinical investigation.

Several countries’ most incorrectly discarded medicines are acetaminophen (ACM), metamizole (MTZ), and nimesulide (NMS). These xenobiotics easily reach the aquatic environment; such contamination is very important for the health of humans and other species, yet little explored. To evaluate the cocktail effect of ACM, MTZ, and NMS during zebrafish’s initial development. Zebrafish embryos 6–8 h post-fertilization (hpf) were exposed to different concentrations of ACM, MTZ, and NMS, separately, to obtain the 50

Mining tailings have a strong presence of heavy metals in their composition, and these elements may be associated with the evolution and spread of antimicrobial resistance. The objective of this work was to analyze studies that describe the relationship between bacteria recovered from sites impacted by mining tailings resulting from the collapse of the Fundão and Córrego do Feijão Mine dams and the development of antimicrobial resistance. This is an integrative literature review, using the PubMed, VHL, Science Direct, and Web of Science databases, and the descriptors “antimicrobial resistance”, “heavy metal”, “dam” and “Brazil” (English) and “resistência antimicrobiana”, “metal pesado”, “barragem” and “Brasil” (Portuguese). Six articles were selected, four referring to the Fundão dam and two to the Córrego do Feijão Mine. All works suggested that environmental contamination by heavy metals, resulting from mining waste released after the dams collapsed, favored the appearance of antimicrobial resistance genes, that is, they are related to the selective pressure exerted by heavy metals. Disasters such as these raise questions about the interface of antimicrobial resistance in environments that have heavy metals as contaminants, the knowledge of which is of great relevance since antimicrobial resistance is a serious public health problem.

O presente estudo teve como objetivo estudar a associação entre a exposição ao glifosato e a ocorrência do Transtorno do Espectro Autista (TEA). Trata-se de um estudo documental com busca de dados acerca da prevalência do TEA (Centers of Disease Control and Prevention) e de um levantamento para verificar o princípio ativo do praguicida mais usado no Brasil (Instituto Brasileiro do Meio Ambiente e dos Recursos Naturais Renováveis) e no mundo (United States Evironmental Prevention Agency). Os resultados mostraram que a prevalência do TEA aumentou ao longo dos anos. Do mesmo modo, o uso e a compra de praguicidas também aumentaram, sendo o glifosato o princípio ativo mais usado. Ainda que os resultados apontem a existência de uma relação entre a exposição ao glifosato e a ocorrência de autismo, são necessários mais estudos para afirmar o potencial neurotóxico do glifosato e sua associação com o nascimento de crianças autistas.

Hydroxychloroquine sulfate (HCQ) and chloroquine diphosphate (CQ) have been used at increased rates to treat COVID-19 but can constitute a potential environmental risk. The objective was to evaluate the toxicity of sublethal concentrations of HCQ and CQ in zebrafish embryos/larvae. The 50% lethal concentrations (LC50) of HCQ and CQ at 96 h post-fertilization (hpf) were calculated by testing various concentrations on 2,160 embryos. The LC50 obtained were 560 and 800 & mu;M for HCQ and CQ, respectively. Next, the embryotoxicity assay was performed, where 1,200 embryos were subjected to sublethal concentrations of HCQ and CQ. The hatching and heart rates were recorded. After euthanasia, photomicrographs of all larvae were taken to measure the total length, pericardial and yolk sac areas. The embryos exposed to sublethal concentrations of HCQ and CQ showed delayed hatching at 72 hpf, as well as an increase in the heart rate, larger pericardial and yolk sac areas, and body malformations at 96 hpf. The findings show that HCQ and CQ are toxic to fish in the early development phases. Understanding the mechanisms of toxicity will help extrapolate the effects of 4-aminoquinoline derivatives when they reach the aquatic environment in the context of the COVID-19 pandemic.

Introduction: Candida albicans is the most common causative agent of Intra-abdominal Candidiasis (IAC) and it is resistant to most antifungal drugs currently available. Here we investigated atorvastatin in vitro and in vivo antifungal activities against a fluconazole-resistant C. albicans strain as a potential repurposed drug. The following tests were carried out: antifungal susceptibility tests to determine minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC), determination of time-kill curve, biofilm assays, Candida albicans yeast-hyphae transition inhibition assay, murine model of Intra-abdominal candidiasis, survival curve, fungal load quantification, histopathology analysis, quantification of TNF-α and IL-17 cytokines, quantification of N-acetyl-β-D-glucosaminidase. In vitro assays showed the synergetic action of atorvastatin and fluconazole against C. albicans growth and biofilm maturation while the time-kill curve assay revealed their fungicidal effect after 24 h of treatment. When yeast-to-hyphae transition was assessed, the synergetic effect of atorvastatin and fluconazole reduced C. albicans filamentation significantly. In vivo tests showed that one of the most noticeable signs of IAC is the intense systemic inflammation. However, our survival curve test showed that despite being ill, animals exhibited little to no clinical signs of systemic inflammation when treatment included a combination of atorvastatin and fluconazole. Altogether, these findings suggest that atorvastatin could be feasibly used in the treatment fluconazole-resistant C. albicans strains, showing that drug repurposing is an important strategy when considering the limited number of antifungal drugs available for treatment in addition to financial hardship experienced in research and development of new antifungal drugs.

Glioblastoma is the most prevalent and malignant brain tumor identified in adults. Surgical resection followed by radiotherapy and chemotherapy, mainly with temozolomide (TMZ), is the chosen treatment for this type of tumor. However, the average survival of patients is around 15 months. Novel approaches to glioblastoma treatment are greatly needed. Here, we aimed to investigate the anti-glioblastoma effect of the combination of matteucinol (Mat) (dihydroxyflavanone derived from Miconia chamissois Naudin) with the chemotherapeutic TMZ in vitro using tumor (U-251MG) and normal astrocyte (NHA) cell lines and in vivo using the chick embryo chorioallantoic membrane (CAM) assay. The combination was cytotoxic and selective for tumor cells (28 μg/mL Mat and 9.71 μg/mL TMZ). Additionally, the combination did not alter cell adhesion but caused morphological changes characteristic of apoptosis in vitro. Notably, the combination was also able to reduce tumor growth in the chick embryo model (CAM assay). The docking results showed that Mat was the best ligand to the cell death membrane receptor TNFR1 and to TNFR1/TMZ complex, suggesting that these two molecules may be working together increasing their potential. In conclusion, Mat-TMZ can be a good candidate for pharmacokinetic studies in view of clinical use for the treatment of glioblastoma.