Search Results (102)

Diseases associated with yeast pathogens have become an increasingly serious global health issue. The range of virulence factors and the development of mechanisms of resistance have posed a significant challenge in the fight against these types of infections. Lectins, proteins capable of reversibly binding to carbohydrates and glycoconjugates, have been assessed as antifungal agents. This review shows that lectins have demonstrated versatility and significant potential as therapeutic agents against Candida, Nakaseomyces and Cryptococcus. These molecules act through diverse mechanisms, including disruption of fungal cell membranes, induction of oxidative stress, inhibition of ergosterol biosynthesis, and interference with mitochondrial and lysosomal functions. Some lectins have been shown to inhibit yeast-to-hyphae morphological transitions and biofilm formation, which are critical virulence factors for pathogenic yeasts. Moreover, some lectins have shown potential to enhance the efficacy of conventional antifungal drugs through synergistic interactions, though these effects can depend on the fungal isolate. Beyond in vitro activity, translational considerations remain underdeveloped in the context of antifungal applications of lectins. Some lectins exhibit minimal toxicity, while others require careful dosing due to potential toxicity or undesired immunogenicity. Delivery and stability also present challenges, though strategies such as chemical modifications and topical, mucosal, or nanoparticle-based formulations show promise. Overall, the multifaceted antifungal activities of lectins highlight their promising role as innovative candidates in the development of novel therapies to address the growing challenge of yeast pathogen resistance. However, significant knowledge gaps persist, highlighting the urgent need for coordinated research that bridges in vitro findings with practical pharmacological applications. Full article

Plants have been used for medicinal purposes both intuitively and based on traditional knowledge for centuries. Recently, however, there has been a significant increase in research focused on medicinal plants to meet the growing demands of the pharmaceutical industry. As a result, it has become essential to evaluate the safety of natural products for human use. This review examines in vitro and in vivo toxicity studies of lectins, a class of plant proteins with pharmacological applications. The reviewed data indicate that many of these proteins do not appear to be toxic to human and animal cells, nor when administered to rodents through oral, intraperitoneal, or intravenous routes. However, some lectins have shown toxicity under certain conditions, such as depending on the administration route, dose, and treatment duration. These adverse effects may include behavioral changes, antinutritional effects, hepatotoxicity, nephrotoxicity, pancreatic hypertrophy, allergic reactions, and even death. Therefore, it is crucial to prioritize toxicological studies to ensure the safety of these plant proteins as potential drug candidates in the future. Full article

Background/Objectives: Colon cancer is the third most common type of cancer in the world, characterized by a high risk of metastasis, resistance to various drugs, and late diagnosis. In addition, the drugs used for treatment are associated with serious neurological damage, causing acute and chronic pain and compromising the patient’s quality of life. Meanwhile, lectins are proteins capable of exerting cytotoxic action on cells from various tumors in a selective manner, without exerting significant toxicity on healthy cells. Despite this, studies on the potential of lectins obtained from microalgae are still scarce in the literature. In this sense, the objective of this study was to evaluate the antitumor activity of lectin isolated from the microalgae Chlorella vulgaris (CvL) on colorectal cancer cells, HT-29. Methods: The purified lectin was tested for cytotoxicity using MTT colorimetric methods, in addition to clonogenicity, cell cycle, apoptosis, and necrosis tests, analyzed by flow cytometry. Results: The assays demonstrated that the lectin was able to induce cell death in the HT-29 tumor line by approximately 83.75% with an IC₅₀ value of 21.5 µg/mL⁻¹, reduced colony formation by more than 90%, was able to regulate the cell cycle by apoptosis, and did not present significant necrosis. These results show that microalgae lectins have the potential to be exploited in the control of neoplastic cells. Full article

Beans are widely consumed worldwide and are a good source of amino acids and micronutrients; however, they contain anti-nutrients, such as lectins, tannins, protein inhibitors, saponins, and phytic acid, among others, which can reduce the food’s quality and cause adverse health effects. In this study, we analyzed the genotoxic and cytotoxic effects of a protein extract from Phaseolus acutifolius (TBE) seeds. The extract contained some antinutritional compounds, with a higher lectin content and an activity of 2701.85 HU. The acute toxicity test in mice showed that the extract was not lethal at the concentrations tested, as it did not cause any mortality. The in vitro cytotoxicity study on small intestinal epithelial cells indicated that the lectin-rich extract was cytotoxic in both assays, with IC₅₀ values of 10.08 µg/mL and 108.91 µg/mL for the free cell and intestinal fragment assays, respectively. In the in vivo study, an erythropoiesis-stimulatory effect was observed, with significant genotoxic damage noted at 48 h, evidenced by 11 micronucleated erythrocytes at 1000 mg/kg TBE. However, no genotoxicity was detected with prolonged treatment times. These results indicate that TBE is cytotoxic within the tested concentration range, and genotoxic damage is influenced by both concentration and exposure time. Full article

Polystyrene microfragments are among the most common plastic pollutants globally. They significantly affect aquatic life, harming various organs and tissues. In this study, we examined the effects of 3 µm polystyrene beads (MPs, 20 µg/L) on development and yolk resorption in pre-feeding nauplii of Artemia salina, a lecithotrophic crustacean used in toxicity testing. Results showed a reduced hatching rate, slower growth, and the onset of oxidative stress. Histological analysis revealed no significant morphological alteration; however, yolk platelets lost N-acetyl galactosamine (galNAc), and resorption was delayed. Lectin staining also showed a reduction in N-acetyl glucosamine (glcNAc) in the gut brush border, indicating impaired gut function. Gas chromatography detected the release of nanogram amounts of toxic volatile compounds (VOCs, ethylbenzene, xylene, benzaldehyde, and styrene) into the culture medium. In conclusion, the data demonstrate a delay in larval yolk resorption that can likely be attributed to the release of VOCs, which induce oxidative stress. Further research is urgently needed, given the potential biological and ecological implications of this finding. Full article

COVID affects around 400 million individuals today with a strong economic impact on the global economy. The list of long COVID symptoms is extremely broad because it is derived from neurological, cardiovascular, respiratory, immune, and renal dysfunctions and damages. We review here these pathophysiological manifestations and the predictors of this multi-organ pathology like the persistence of the virus, altered endothelial function, unrepaired tissue damage, immune dysregulation, and gut dysbiosis. We also discuss the similarities between long COVID and vaccine side effects together with possible common immuno-inflammatory pathways. Since the spike protein is present in SARS-CoV-2 (and its variants) but also produced by the COVID vaccines, its toxicity may also apply to all mRNA or adenoviral DNA vaccines as they are based on the production of a very similar spike protein to the virus. After COVID infection or vaccination, the spike protein can last for months in the body and may interact with ACE2 receptors and mannan-binding lectin (MBL)/mannan-binding lectin serine protease 2 (MASP-2), which are present almost everywhere in the organism. As a result, the spike protein may be able to trigger inflammation in a lot of organs and systems similar to COVID infection. We suggest that three immuno-inflammatory pathways are particularly key and responsible for long COVID and COVID vaccine side effects, as it has been shown for COVID, which may explain in large part their strong similarities: the renin–angiotensin–aldosterone system (RAAS), the kininogen–kinin–kallikrein system (KKS), and the lectin complement pathway. We propose that therapeutic studies should focus on these pathways to propose better cures for both long COVID as well as for COVID vaccine side effects. Full article

Ricin, a type 2 ribosome-inactivating protein, is a lethal toxin found in castor bean seeds. Although the systemic toxicity of ricin has been extensively studied, its localized effect on the gastrointestinal tract remains a critical concern, particularly in the case of oral ingestion. This study investigates the cytotoxic effects of ricin on human intestinal epithelial cell lines and its impact on epithelial barrier integrity. Ricin cytotoxicity was assessed on the intestinal-derived HT29 and Caco-2 cell lines using dose– and time–response assays, while the epithelial integrity was evaluated via Trans-Epithelial Electrical Resistance (TEER) measurements in Caco-2 monolayers. Cell death was determined through flow cytometry analysis, and the protective effects of cell death inhibitors and antioxidant scavengers were investigated on ricin-intoxicated cells. Ricin showed high cytotoxicity on HT29 and Caco-2 cells, with EC₅₀ values in the nM range after 24–72 h of intoxication. Moreover, ricin strongly reduced TEER values in Caco-2 cells at 0.1–1 nM after 24 h of treatment. At a 1 nM concentration, ricin cytotoxicity can be significantly prevented by pre-incubating cells with the cell death inhibitors Z-VAD or necrostatin-1 and the antioxidant scavenger catalase, butylated hydroxyanisole or sodium pyruvate, demonstrating the involvement of apoptosis/necroptosis and oxidative stress in ricin cell death pathways and mechanisms. Full article

In the present study, for the first time, a biodegradable and non-toxic polyphosphoramidate glycohydrogel (PPAGHGel) was prepared by crosslinking a polyphosphoramidate glycoconjugate (PPAG) with hexamethylene diisocyanate (HMDI) under mild conditions. Poly(oxyethylene H-phosphonate) (POEHP) was used as a precursor and was converted into PPAG via the Staudinger reaction with glucose-containing azide (2-p-azidobenzamide-2-deoxy-1,3,4,6-tetra-O-trimethylsilyl-α-D-glucopyranose). Then, crosslinking of PPAG was performed to yield PPAGHGel, which was thoroughly characterized. The gel showed a gel fraction of 83%, a swelling degree of 1426 ± 98%, and G″ = 1560 ± 65 Pa. The gel was fully degraded by alkaline phosphatase (400 U/L, pH 9) in 19 days, while hydrolytically, up to 52% degradation was observed under similar conditions. Multivalent studies of the obtained hydrogel with lectin–Concanavalin A were performed. PPAGHGel binds 92% of Concanavalin A within 24 h and the complex remains stable until the amount of glucose reaches 0.3 mM. PPAGHGel acts as a stabilizer for silver nanoparticles (12 nm). SEM shows pores measuring 10 µm (surface) and 0.1 mm (interior) with capillary channels, confirming the gel’s suitability for biosensors, drug delivery, or wound dressings. The cytotoxic (IC50) and cell-adhesive properties of the obtained hydrogel were investigated on human cell lines (HeLa). Antibacterial activity tests were also performed with gel containing silver nanoparticles against skin-associated pathogenic bacteria. The results show that PPAGHGel possesses excellent biocompatibility, non-adhesive properties and antibacterial activity. Full article

Euphorbia hirta L. is traditionally used to treat tumors and has demonstrated anticancer effects. This study evaluated the phytochemical composition, toxicity, and antitumor activity of saline extract (SE) from E. hirta leaves in mice. Phytochemical analysis included thin layer chromatography, high-performance liquid chromatography, and quantification of phenols, flavonoids, and proteins. Acute toxicity (2000 mg/kg) assessed mortality, hematological, biochemical, histological parameters, water/feed intake, and body weight. Genotoxicity was evaluated via comet and micronucleus assays. Antitumor activity was tested in vitro and in vivo on sarcoma 180. SE contained 107.3 mg GAE/g phenolics and 22.9 mg QE/g flavonoids; the presence of gallic and ellagic acids was detected. Protein concentration was 12.16 mg/mL with lectin activity present. No mortality, organ damage, or genotoxic effects occurred in toxicity tests. SE demonstrated in vitro cytotoxicity against sarcoma cells (IC₅₀: 10 µg/mL). In vivo, SE (50–200 mg/kg) reduced tumor weight by 70.2–72.3%. SE modulated IL-2, IL-4, IL-6, IL-17, IFN-γ, and TNF-α in tumor environment. Tumors showed inflammatory infiltrate, necrosis, and fibrosis after treatment. These findings position the extract as a promising candidate for further development as a safe, plant-based antitumor agent. Full article

Snakebite remains the most neglected tropical disease globally, with India experiencing the highest rates of mortality and morbidity. While most envenomation cases in India are attributed to the ‘big four’ snakes, research has predominantly focused on Russell’s viper (Daboia russelii), spectacled cobra (Naja naja), and common krait (Bungarus caeruleus), leading to a considerable gap in our understanding of saw-scaled viper (Echis carinatus carinatus) venoms. For instance, the venom gland transcriptome and inter- and intra-population venom variation in E. c. carinatus have largely remained uninvestigated. A single study to date has assessed the effectiveness of commercial antivenoms against this species under in vivo conditions. To address these crucial knowledge gaps, we conducted a detailed investigation of E. c. carinatus venom and reported the first venom gland transcriptome. A proteotranscriptomic evaluation revealed snake venom metalloproteinases, C-type lectins, L-amino acid oxidases, phospholipase A₂s, and snake venom serine proteases as the major toxins. Moreover, we assessed the intra-population venom variation in this species using an array of biochemical analyses. Finally, we determined the venom toxicity and the neutralising efficacy of a commercial antivenom using a murine model of snake envenoming. Our results provide a thorough molecular and functional profile of E. c. carinatus venom. Full article

Viscum coloratum (Komar.) Nakai (V. coloratum) is a traditional Chinese herbal medicine. It is used in treating rheumatism and paralysis, lumbar and knee soreness, weakness of the muscles and bones, excessive leakage of menstruation, leakage of blood in pregnancy, restlessness of the fetus, dizziness and vertigo. All information about V. coloratum was collected through databases such as PubMed, Google Scholar, Web of Science, and the China National Knowledge Infrastructure and supplemented by consulting classical Chinese medical books. To date, 111 compounds have been isolated and identified from V. coloratum, including flavonoids, phenylpropanoids, terpenoids, diarylheptanoids, alkaloids, other components, and macromolecular compounds, such as polysaccharides and lectins. These chemical components exhibit anti-inflammatory, anticancer, antioxidant, and anti-cardiovascular disease effects, among other beneficial effects. According to the reports, alkaloids, lectins, and other chemical components present in V. coloratum may induce toxicity due to excessive intake or accidental ingestion. However, there are few reports on the toxicology of V. coloratum, and there is a lack of studies on the toxicity of V. coloratum with known in vitro or preclinical activity. It is suggested that further studies on the toxicology of V. coloratum should be conducted in the future. In this paper, the botany, traditional uses, phytochemistry, pharmacology, and pharmacokinetics of V. coloratum are summarized, and the progress and shortcomings in toxicology are discussed, so as to provide a possible direction for future research on V. coloratum. Full article

The perivitellin-2 (PV2) from snails is an unusual neuro and enterotoxin comprising a pore-forming domain of the Membrane Attack Complex and Perforin Family (MACPF) linked to a lectin. While both domains have membrane binding capabilities, PV2’s mechanism of action remains unclear. We studied the apple snail Pomacea maculata PV2’s (PmPV2’s) interaction with lipid membranes using various biophysical and cell biology approaches. In vitro studies showed that PmPV2 toxicity decreased when cholesterol (Chol) was diminished from enterocyte cell membranes. Chol enhanced PmPV2 association with phosphatidylcholine membranes but did not induce pore formation. In contrast, using rat brain lipid models, rich in glycolipids, PmPV2 exhibited high affinity and induced vesicle permeabilization. Negative stain electron microscopy and atomic force microscopy confirmed the formation of pore-like structures in brain lipid vesicles. Our findings suggest that Chol is a necessary lipid component and point to PmPV2–glycolipid interactions as potential activators critical to triggering PmPV2’s pore-forming activity, providing insights into this novel toxin’s mechanism. Full article

This study documents the Euphorbiaceae family of plants in Southern Africa, with a focus on their traditional medicinal applications, pharmacological properties, toxicity, and active secondary metabolites. A review of the literature from scientific journals, books, dissertations, and conference papers spanning from 1962 to 2023 was conducted for 15 Euphorbia species. Recent findings indicate that specific compounds found in Euphorbia plants exhibit significant biological and pharmacological properties. However, the white sticky latex sap they contain is highly toxic, although it may also have medicinal applications. Phytochemical analyses have demonstrated that these plants exhibit beneficial effects, including antibacterial, antioxidant, antiproliferative, anticancer, anti-inflammatory, antiviral, antifungal, and anti-HIV activities. Key phytochemicals such as euphol, cycloartenol, tirucallol, and triterpenoids contribute to their therapeutic efficacy, along with various proteins like lectin and lysozyme. Despite some Euphorbiaceae species undergoing screening for medicinal compounds, many remain insufficiently examined, highlighting a critical gap in the research literature. Given their historical usage, further investigations are essential to evaluate the medicinal significance of Euphorbia species through detailed studies of isolated compounds and their pharmacokinetics and pharmacodynamics. This research will serve as a valuable resource for future inquiries into the benefits of lesser-studied Euphorbia species. Full article

Previous proteomic studies of viperid venom revealed that it is mainly composed of metalloproteinases (SVMPs), serine proteinases (SVSPs), phospholipase A2 (PLA2), and C-type lectins (CTLs). However, other proteins appear in minor amounts that affect prey and need to be identified. This study aimed to identify novel toxic proteins in the venom gland transcriptome of Bothrops asper and Bothrops jararaca, using data from NCBI. Bioinformatics tools were used to assemble, identify, and compare potentially novel proteins in both species, and we performed functional annotation with BLASTX against the NR database. While previous assemblies have been performed for B. jararaca, this is the first assembly of the B. asper venom gland transcriptome. Proteins with potentially novel functions were identified, including arylsulfatase and dihydroorotate dehydrogenase, among others, that could have implications for venom toxicity. These results suggest that the identified proteins may contribute to venom toxic variation and provide new opportunities for antivenom research. The study improves the understanding of the protein composition of Bothrops venom and suggests new possibilities for the development of treatments and antivenoms. Full article

Background: Glioblastoma (GBM) uses Glut3 and/or Glut14 and the Leloir pathway to catabolize D-Galactose (Gal). UDP-4-deoxy-4-fluorogalactose (UDP-4DFG) is a potent inhibitor of the two key enzymes, UDP-galactose-4-epimerase (GALE) and UDP-Glucose 6-dehydrogenase (UGDH), involved in Gal metabolism and in glycan synthesis. The Gal antimetabolite 4-deoxy-4-fluorogalactose (4DFG) is a good substrate for Glut3/Glut14 and acts as a potent glioma chemotherapeutic. Methods: Primary GBM cell cultures were used to examine toxicity and alterations in glycan composition via lectin binding in fixed cells and by Western blots. Toxicity/efficacy in vivo data was performed in mouse flank and intracranial models. The effect of 4DFG on D-glucose (Glc) metabolism in GBM cells was assessed by using ¹³C NMR-based tracer studies. Results: 4DFG is moderately potent against GBM cells (IC₅₀: 125–300 µM). GBM glycosylation is disrupted by 4DFG. Survival analysis in an intracranial mouse model showed that treatment with 4DFG (6 × 25 mg/kg of 4DFG, intravenously) improved outcomes by three-fold (p < 0.01). Metabolic flux analysis revealed that both glycolytic and mitochondrial metabolic fluxes of [U-¹³C]Glc were significantly decreased in the presence of 4DFG in GBM cells. Conclusion: A functional Gal-scavenging pathway in GBM allows Gal-based antimetabolites to act as chemotherapeutics. 4DFG is metabolized by GBM in vitro and in vivo, is lethal to GBM tumors, and is well tolerated in mice. Full article