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Fungal infections are becoming a serious problem of human diseases, being one of the most important fungal pathogens the yeast of the genus Candida. So far, fungal infection treatment faces different challenges, including the limited... more
Fungal infections are becoming a serious problem of human diseases, being one of the most important fungal pathogens the yeast of the genus Candida. So far, fungal infection treatment faces different challenges, including the limited number of therapeutic drugs. Scorpions are known to be a valuable source of biologically active molecules, especially of peptide-derived molecules with a variety of biological effects and useful, lead compounds for drugs development. Here, we pioneer described the antifungal effect of venom, mucus, and the major toxin (Rc1) from Rhopalurus crassicauda scorpion. These results support the potential for Rc1 to be further investigated as a novel antifungal therapeutic to treat Candida infections.
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Tityus serrulatus (Ts) is the main scorpion species of medical importance in Brazil. Ts venom is composed of several compounds such as mucus, inorganic salts, lipids, amines, nucleotides, enzymes, kallikrein inhibitor, natriuretic... more
Tityus serrulatus (Ts) is the main scorpion species of medical importance in Brazil. Ts venom is composed of several compounds such as mucus, inorganic salts, lipids, amines, nucleotides, enzymes, kallikrein inhibitor, natriuretic peptide, proteins with high molecular mass, peptides, free amino acids and neurotoxins. Neurotoxins are considered the most responsible for the envenoming syndrome due to their pharmacological action on ion channels such as voltage-gated sodium (Nav) and potassium (Kv) channels. The major goal of this review is to present important advances in Ts envenoming research, correlating both the crude Ts venom and isolated toxins with alterations observed in all human systems. The most remarkable event lies in the Ts induced massive releasing of neurotransmitters influencing, directly or indirectly, the entire body. Ts venom proved to extremely affect nervous and muscular systems, to modulate the immune system, to induce cardiac disorders, to cause pulmonary edema, to decrease urinary flow and to alter endocrine, exocrine, reproductive, integumentary, skeletal and digestive functions. Therefore, Ts venom possesses toxins affecting all anatomic systems, making it a lethal cocktail. However, its low lethality may be due to the low venom mass injected, to the different venom compositions, the body characteristics and health conditions of the victim and the local of Ts sting. Furthermore, we also described the different treatments employed during envenoming cases. In particular, throughout the review, an effort will be made to provide information from an extensive documented studies concerning Ts in vitro, in animals and in humans (a total of 151 references). Over the past three decades (since 1981), our research team has undertaken several studies involving the isolation, purification and characterization of toxins from the Brazilian yellow scorpion Tityus serrulatus (Ts). The present review deals with Ts venom and toxins studies and focuses on their effects on all anatomic systems. Indeed, different human systems are known to be affected by Ts venom components. In this research, we review and discuss the clinical/laboratorial manifestations and pathophysiology of Ts envenoming on the different anatomical systems: nervous, muscular, immune, cardiovascular, respiratory, urinary, endocrine and exocrine, digestive, integumentary, skeletal and reproductive systems. All this modulating and blocking action of Ts neurotoxins on ion channels can be correlated with the effects on neurons and skeletal muscles.
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Research Interests: Bioinformatics, Chemistry, Immunology, Immunotoxicology, Immune response, and 15 moreBiology, Inflammation, Chemical Biology, Biological Sciences, Clinical immunology, Biomedical Research, Anatomy and Physiology, Immunity, Animals, CD, Immune system, Immune activation, Immune cells, clinical laboratory sciences, and Inflammation Mediators
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Snake venom serine proteases (SVSPs) are complex and multifunctional enzymes, acting primarily on hemostasis. In this work, we report the hitherto unknown inhibitory effect of a SVSP, named collinein-1, isolated from the venom of Crotalus... more
Snake venom serine proteases (SVSPs) are complex and multifunctional enzymes, acting primarily on hemostasis. In this work, we report the hitherto unknown inhibitory effect of a SVSP, named collinein-1, isolated from the venom of Crotalus durissus collilineatus, on a cancer-relevant voltage-gated potassium channel (hEAG1). Among 12 voltage-gated ion channels tested, collinein-1 selectively inhibited hEAG1 currents, with a mechanism independent of its enzymatic activity. Corroboratively, we demonstrated that collinein-1 reduced the viability of human breast cancer cell line MCF7 (high expression of hEAG1), but does not affect the liver carcinoma and the non-tumorigenic epithelial breast cell lines (HepG2 and MCF10A, respectively), which present low expression of hEAG1. In order to obtain both functional and structural validation of this unexpected discovery, where an unusually large ligand acts as an inhibitor of an ion channel, a recombinant and catalytically inactive mutant of coll...
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Research Interests: Biochemistry, Skeletal muscle biology, Biology, Medicine, Platelet aggregation, and 15 moreSequence alignment, Mice, Animals, Male, Venom, Creatine Kinase, Enzyme, Snake Venom, Crotalus, Skeletal Muscle, Edema, Amino Acid Sequence, Biochemistry and cell biology, Molecular Sequence Data, and Phospholipase
Snake venoms present a great diversity of pharmacologically active compounds that may be applied as research and biotechnological tools, as well as in drug development and diagnostic tests for certain diseases. The most abundant toxins... more
Snake venoms present a great diversity of pharmacologically active compounds that may be applied as research and biotechnological tools, as well as in drug development and diagnostic tests for certain diseases. The most abundant toxins have been extensively studied in the last decades and some of them have already been used for different purposes. Nevertheless, most of the minor snake venom protein classes remain poorly explored, even presenting potential application in diverse areas. The main difficulty in studying these proteins lies on the impossibility of obtaining sufficient amounts of them for a comprehensive investigation. The advent of more sensitive techniques in the last few years allowed the discovery of new venom components and the in-depth study of some already known minor proteins. This review summarizes information regarding some structural and functional aspects of low abundant snake venom proteins classes, such as growth factors, hyaluronidases, cysteine-rich secret...
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Scorpion sting envenomations (SSE) are feared by the intense pain that they produce in victims. Pain from SSE is triggered mainly by the presence of neurotoxins in the scorpion venom that modulates voltage-gated ion channels. In Brazil,... more
Scorpion sting envenomations (SSE) are feared by the intense pain that they produce in victims. Pain from SSE is triggered mainly by the presence of neurotoxins in the scorpion venom that modulates voltage-gated ion channels. In Brazil, SSE is mostly caused by Tityus serrulatus, popularly known as yellow scorpion. Here, we evaluated experimental spontaneous nociception induced by T. serrulatus venom as well as its isolated neurotoxins Ts1, Ts5, Ts6, Ts8, and Ts19 frag II, evidencing different degrees of pain behavior in mice. In addition, we developed a mice-derived polyclonal antibody targeting Ts5 able to neutralize the effect of this neurotoxin, showing that Ts5 presents epitopes capable of activating the immune response, which decreased considerably the nociception produced by the whole venom. This is the pioneer study to explore nociception using different classes of T. serrulatus neurotoxins on nociception (α-NaTx, β-NaTx, α-KTx, and β-KTx), targeting potassium and sodium volt...
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Poison inhibitory assays. (DOCX 725 kb)
Protease production was carried out in solid state fermentation. The enzyme was purified through precipitation with ethanol at 72% followed by chromatographies in columns of Sephadex G75 and Sephacryl S100. It was purified 80-fold and... more
Protease production was carried out in solid state fermentation. The enzyme was purified through precipitation with ethanol at 72% followed by chromatographies in columns of Sephadex G75 and Sephacryl S100. It was purified 80-fold and exhibited recovery of total activity of 0.4%. SDS-PAGE analysis indicated an estimated molecular mass of 24.5 kDa and the N-terminal sequence of the first 22 residues was APYSGYQCSMQLCLTCALMNCA. Purified protease was only inhibited by EDTA (96.7%) and stimulated by Fe2þ revealing to be a metalloprotease activated by iron. Optimum pH was 5.5, optimum temperature was 75 C, and it was thermostable at 65 C for 1 h maintaining more than 70% of original activity. Through enzyme kinetic studies, protease better hydrolyzed casein than azocasein. The screening of fluorescence resonance energy transfer (FRET) peptide series derived from Abz-KLXSSKQ-EDDnp revealed that the enzyme exhibited preference for Arg in P1 (kcat/Km = 30.1 mM-1 s-1).
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Four toxic, electrophoretically homogeneous proteins were isolated by ion-exchange chromatography on CM-cellulose-52 from the venom of the scorpion Tityus discrepans (range North Central Venezuela), named TdIV, TdV, TdVIII and TdIX.... more
Four toxic, electrophoretically homogeneous proteins were isolated by ion-exchange chromatography on CM-cellulose-52 from the venom of the scorpion Tityus discrepans (range North Central Venezuela), named TdIV, TdV, TdVIII and TdIX. Component TdVIII, with 56 amino acid residues and mol. wt 6140 was the most toxic by i.p. injections into mice and had an intracisternal LD50 of 7.9 micrograms protein/kg body weight. Amino acid compositions of components TdIV and TdV were very similar, suggesting that they could be highly homologous proteins, although presumably contaminated one by the other. A fifth component, named TdIII, non-toxic by i.p. injections, was also isolated in homogeneous form. The i.v. and intracisternal LD50 values of the whole T. discrepans venom were 2.5 mg/kg and 16.0 micrograms/kg, respectively.
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Representative picture showing forward/side scatter dot-plot of human PBMC treated with TsV. Peripheral blood mononuclear cells (PBMC; 2 × 106 cells/mL) were cultured with Tityus serrulatus scorpion venom (TsV; 25, 50, and 100 μg/mL),... more
Representative picture showing forward/side scatter dot-plot of human PBMC treated with TsV. Peripheral blood mononuclear cells (PBMC; 2 × 106 cells/mL) were cultured with Tityus serrulatus scorpion venom (TsV; 25, 50, and 100 μg/mL), phytohemagglutinin (PHA; 2 μg/mL; positive control) for 24 h, at 37 °C, and under 5 % CO2. Untreated PBMC represents the negative control. PBMC were labeled with anti-CD3/FITC and anti-CD8/PE monoclonal antibodies and further analyzed by flow cytometry. The lymphocyte gate was selected and analyzed to calculate the percentage of stained cells. The figure depicts a representative analysis from six independent experiments. The percentages in parentheses refer to CD3+ CD8+ cells (P2 region). (A) Negative control (5.5 %). (B) PHA-stimulated cells (26.1 %). (C) 100 μg/mL of TsV (4.9 %). (D) 50 μg/mL of TsV (6.4 %). (E) 25 μg/mL of TsV (8.4 %). (DOCX 204 kb)
Research Interests: Pharmacology, Biochemistry, Microbiology, Physiology, Inorganic Chemistry, and 15 moreHematology, Developmental Biology, Immunology, Molecular Biology, Mental Health, Computational Biology, Cancer, Virology, Cell Biology, Infectious Diseases, Space Science, Immunomodulation, Cytokine, Immunophenotyping, and Cell Proliferation
Representative comparison of eyeball of Ts envenomed and non-envenomed mice. Mice were injected with Ts venom (1 mg/kg). (A) Envenomed NOD mice with glucose basal level ≥ 200 mg/dL, retinopathy indication. (B) Envenomed BALB/c mice,... more
Representative comparison of eyeball of Ts envenomed and non-envenomed mice. Mice were injected with Ts venom (1 mg/kg). (A) Envenomed NOD mice with glucose basal level ≥ 200 mg/dL, retinopathy indication. (B) Envenomed BALB/c mice, typical ptosis. (C) BALB/c mice control (non-envenomed), normal eyeball. (PPTX 81 kb)
Eletrophoretic profile of Rhinella schneideri's cutaneous secretion. Different volumes (5, 10 and 20 µL) of CS were analyzed by 12,5 % SDS-PAGE and stained with Coomasie Blue PhastGel ™ R-350. MW-molecular weight marker; 5 µL- 5 µL of... more
Eletrophoretic profile of Rhinella schneideri's cutaneous secretion. Different volumes (5, 10 and 20 µL) of CS were analyzed by 12,5 % SDS-PAGE and stained with Coomasie Blue PhastGel ™ R-350. MW-molecular weight marker; 5 µL- 5 µL of CS; 10 µL- 10 µL of CS; 20 µL – 20 µLof CS. All the samples were reduced in the presence of β-mercaptoethanol and boiled for 10 minutes befora application in the SDS-PAGE. (PPTX 189 kb)
Gene ontology of Rhinella schneideri skin transcriptome. The Gene Ontology is divided in biological proccess, molecular function and cellular component. (DOCX 13 kb)
Peptide assignment of N. villosa venom extracted during winter and summer identified by nano-LC-ESI-MS/MS. (DOCX 13 kb)
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Tityus serrulatus (Ts) is the main scorpion species of medical importance in Brazil. Ts venom is composed of several compounds such as mucus, inorganic salts, lipids, amines, nucleotides, enzymes, kallikrein inhibitor, natriuretic... more
Tityus serrulatus (Ts) is the main scorpion species of medical importance in Brazil. Ts venom is composed of several compounds such as mucus, inorganic salts, lipids, amines, nucleotides, enzymes, kallikrein inhibitor, natriuretic peptide, proteins with high molecular mass, peptides, free amino acids and neurotoxins. Neurotoxins are considered the most responsible for the envenoming syndrome due to their pharmacological action on ion channels such as voltage-gated sodium (Nav) and potassium (Kv) channels. The major goal of this review is to present important advances in Ts envenoming research, correlating both the crude Ts venom and isolated toxins with alterations observed in all human systems. The most remarkable event lies in the Ts induced massive releasing of neurotransmitters influencing, directly or indirectly, the entire body. Ts venom proved to extremely affect nervous and muscular systems, to modulate the immune system, to induce cardiac disorders, to cause pulmonary edema, to decrease urinary flow and to alter endocrine, exocrine, reproductive, integumentary, skeletal and digestive functions. Therefore, Ts venom possesses toxins affecting all anatomic systems, making it a lethal cocktail. However, its low lethality may be due to the low venom mass injected, to the different venom compositions, the body characteristics and health conditions of the victim and the local of Ts sting. Furthermore, we also described the different treatments employed during envenoming cases. In particular, throughout the review, an effort will be made to provide information from an extensive documented studies concerning Ts in vitro, in animals and in humans (a total of 151 references). Over the past three decades (since 1981), our research team has undertaken several studies involving the isolation, purification and characterization of toxins from the Brazilian yellow scorpion Tityus serrulatus (Ts). The present review deals with Ts venom and toxins studies and focuses on their effects on all anatomic systems. Indeed, different human systems are known to be affected by Ts venom components. In this research, we review and discuss the clinical/laboratorial manifestations and pathophysiology of Ts envenoming on the different anatomical systems: nervous, muscular, immune, cardiovascular, respiratory, urinary, endocrine and exocrine, digestive, integumentary, skeletal and reproductive systems. All this modulating and blocking action of Ts neurotoxins on ion channels can be correlated with the effects on neurons and skeletal muscles.
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Tityus serrulatus (Ts) venom is composed of mainly neurotoxins specific for voltage-gated K(+) and Na(+) channels, which are expressed in many cells such as macrophages. Macrophages are the first line of defense invasion and they... more
Tityus serrulatus (Ts) venom is composed of mainly neurotoxins specific for voltage-gated K(+) and Na(+) channels, which are expressed in many cells such as macrophages. Macrophages are the first line of defense invasion and they participate in the inflammatory response of Ts envenoming. However, little is known about the effect of Ts toxins on macrophage activation. This study investigated the effect of Ts5 toxin on different sodium channels as well as its role on the macrophage immunomodulation. The electrophysiological assays showed that Ts5 inhibits the rapid inactivation of the mammalian sodium channels Nav1.2, Nav1.3, Nav1.4, Nav1.5, Nav1.6 and Nav1.7. Interestingly, Ts5 also inhibits the inactivation of the insect Drosophila melanogaster sodium channel (DmNav1), and is therefore classified as the first Ts α-like toxin. The immunological experiments on macrophages reveal that Ts5 is a pro-inflammatory toxin inducing the cytokine production of tumor necrosis factor (TNF)-α and ...
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Research Interests: Chemistry, Biomedical Engineering, Scanning Electron Microscopy, Medicine, Cytoskeleton, and 15 moreCell line, Pulmonary fibrosis, Collagen, Animals, Pneumonia, Solubility, Cattle, Hyaluronic Acid, Particle Size, Microspheres, Lactic Acid, Static Electricity, Phagocytes, Biochemistry and cell biology, and Cell count
Bothrops asper(Squamata: Viperidae) is the most important venomous snake in Central America, being responsible for the majority of snakebite accidents. Four basic PLA2s (pMTX-I to -IV) were purified from crude venom by a single-step... more
Bothrops asper(Squamata: Viperidae) is the most important venomous snake in Central America, being responsible for the majority of snakebite accidents. Four basic PLA2s (pMTX-I to -IV) were purified from crude venom by a single-step chromatography using a CM-Sepharose ion-exchange column (1.5 × 15 cm). Analysis of the N-terminal sequence demonstrated that pMTX-I and III belong to the catalytically active Asp49 phospholipase A2subclass, whereas pMTX-II and IV belong to the enzymatically inactive Lys49 PLA2s-like subclass. The PLA2s isolated from PanamaBothrops aspervenom (pMTX-I, II, III, and IV) are able to induce myotoxic activity, inflammatory reaction mainly leukocyte migration to the muscle, and induce J774A.1 macrophages activation to start phagocytic activity and superoxide production.