Disintegrin-like Protein Strategy to Inhibit Aggressive Triple-Negative Breast Cancer.

Venoms are a rich source of bioactive compounds, and among them is leberagin-C (Leb-C), a disintegrin-like protein derived from the venom of snakes. Leb-C has shown promising inhibitory effects on platelet aggregation. Previous studies have demonstrated that this SECD protein specifically targets α5β1, αvβ3, and αvβ6 integrins through a mimic mechanism of RGD disintegrins.

Determination of Local Electrical Properties Using a Potential Field Measurement for Electrically Conductive Carbon Fiber Reinforced Plastics with Metal Contact Pins Joined via Injection Molding.

Carbon fiber reinforced plastics (CFRP) bear a high potential in terms of electrical conductivity and its potential applications. A locally resolved electrical measurement method for these anisotropic materials is a key prerequisite for understanding the structural and manufacturing process-related interrelationships. The aim of this paper is to develop a measurement method that allows this to be achieved and also to investigate areas of overmolded metal contact pins in detail.

Neutralizing Dromedary-Derived Nanobodies Against BotI-Like Toxin From the Most Hazardous Scorpion Venom in the Middle East and North Africa Region.

Scorpion envenoming is a severe health problem in many regions causing significant clinical toxic effects and fatalities. In the Middle East/North Africa (MENA) region, scorpion stings are responsible for devastating toxic outcomes in human. The only available specific immunotherapeutic treatment is based on IgG fragments of animal origin.

First Evidence of Kv3.1b Potassium Channel Subtype Expression during Neuronal Serotonergic 1C11 Cell Line Development.

Kv3.1 channel is abundantly expressed in neurons and its dysfunction causes sleep loss, neurodegenerative diseases and depression. Fluoxetine, a serotonin selective reuptake inhibitor commonly used to treat depression, acts also on Kv3.

Targeting α1 inserted domain (I) of α1β1 integrin by Lebetin 2 from M. lebetina transmediterranea venom decreased tumorigenesis and angiogenesis.

Through the recent development of knowledge in biotechnology and bioinformatics, snake venoms are widely used to develop new drugs to treat diseases such as hypertension and cancer. We have previously reported that Lebetin 2 isolated from Macrovipera lebetina transmediterranea venom displays a potent anti-platelet activity and exerts a cardioprotective effect in ischemia-reperfusion (IR) injury model. Here, we report that Lebetin 2 possess an anti-tumor effect by targeting the integrin receptor function.

Modulation of Kv3.1b potassium channel level and intracellular potassium concentration in 158N murine oligodendrocytes and BV-2 murine microglial cells treated with 7-ketocholesterol, 24S-hydroxycholesterol or tetracosanoic acid (C24:0).

Little is known about K regulation playing major roles in the propagation of nerve impulses, as well as in apoptosis and inflammasome activation involved in neurodegeneration. As increased levels of 7-ketocholesterol (7KC), 24S-hydroxycholesterol (24S-OHC) and tetracosanoic acid (C24:0) have been observed in patients with neurodegenerative diseases, we studied the effect of 24 and/or 48 h of treatment with 7KC, 24S-OHC and C24:0 on Kv3.1b potassium channel level, intracellular K concentration, oxidative stress, mitochondrial dysfunction, and plasma membrane permeability in 158N oligodendrocytes and BV-2 microglial cells.

Hyalomma dromedarii (Acari: Ixodidae) Salivary Gland Extract Inhibits Angiogenesis and Exhibits In Vitro Antitumor Effects.

Hard ticks (Acari: Ixodidae) are blood-sucking ectoparasites characterized by the extended period of their attachment to their host. To access their bloodmeal, ticks secrete saliva containing a range of molecules that target the host's inflammation, immune system, and hemostatic components. Some of these molecules reportedly possess antiangiogenic and antitumor properties.

Lipid Biomarkers in Alzheimer's Disease.

Background: There are now significant evidences that lipid metabolism is affected in numerous neurodegenerative diseases including Alzheimer's disease. These dysfunctions lead to abnormal levels of certain lipids in the brain, cerebrospinal fluid and plasma. It is consequently of interest to establish lipid profiles in neurodegenerative diseases.

Evidence of K homeostasis disruption in cellular dysfunction triggered by 7-ketocholesterol, 24S-hydroxycholesterol, and tetracosanoic acid (C24:0) in 158N murine oligodendrocytes.

Imbalance in the homeostasis of K ions has been reported to contribute to the pathogenesis of neurodegenerative diseases. 7-ketocholesterol (7KC), 24S-hydroxycholesterol (24S-OHC), and tetracosanoic acid (C24:0), often found at increased levels in patients with Alzheimer's disease, Multiple Sclerosis and X-ALD, are able to trigger numerous nerve cell dysfunctions. We therefore studied the impact of 7KC, 24S-OHC, and C24:0 on 158N murine oligodendrocytes, and determined their impact on K homeostasis.

The small subunit of Hemilipin2, a new heterodimeric phospholipase A2 from Hemiscorpius lepturus scorpion venom, mediates the antiangiogenic effect of the whole protein.

In a previous study, we reported the identification of Hemilipin, the first secreted heterodimeric phospholipase A2 (sPLA2) from Hemiscorpius lepturus scorpion venom and demonstrated its effective inhibition of all angiogenesis key steps in vitro and in vivo. Here, we aimed to characterize a second sPLA, Hemilipin2, from the same venom and to elucidate its antiangiogenic effect. The protein was purified by chromatography separation and analyzed by MALDI/TOF mass spectrometry.

Dromedary immune response and specific Kv2.1 antibody generation using a specific immunization approach.

Voltage-gated potassium (Kv) channels form cells repolarizing power and are commonly expressed in excitable cells. In non-excitable cells, Kv channels such as Kv2.1 are involved in cell differentiation and growth.

Biochemical and monolayer characterization of Tunisian snake venom phospholipases.

The present study investigated the kinetic and interfacial properties of two secreted phospholipases isolated from Tunisian vipers'venoms: Cerastes cerastes (CC-PLA2) and Macrovipera lebetina transmediterranea (MVL-PLA2). Results show that these enzymes have great different abilities to bind and hydrolyse phospholipids. Using egg-yolk emulsions as substrate at pH 8, we found that MVL-PLA2 has a specific activity of 1473U/mg at 37°C in presence of 1mM CaCl2.

Interaction of a snake venom L-amino acid oxidase with different cell types membrane.

Snake venom l-amino acid oxidases are multifunctional enzymes that exhibited a wide range of pharmacological activities. Although it has been established that these activities are primarily caused by the H2O2 generated in the enzymatic reaction, the molecular mechanism, however, has not been fully investigated. In this work, LAAO interaction with cytoplasmic membranes using different cell types and Langmuir interfacial monolayers was evaluated.

Hemilipin, a novel Hemiscorpius lepturus venom heterodimeric phospholipase A2, which inhibits angiogenesis in vitro and in vivo.

Phospholipases A2 (PLA2) are enzymes which specifically hydrolyze the sn-2 acyl ester bond of phospholipids producing free fatty acids and lysophospholipids. The secreted PLA2 (sPLA2) are the most common types of PLA2 purified from the snake venom, mammalian pancreatic juice and other sources. They display a variety of toxic actions and biological activities, including antitumoral and antiangiogenic effects.

Phthalimido-ferrocidiphenol cyclodextrin complexes: Characterization and anticancer activity.

Several ferrocenyl analogues of tamoxifen have already showed strong antiproliferative activity in experimental glioma models. Nevertheless, these compounds are very poorly soluble in water and an adapted formulation is needed. In this work, we have tailored and optimized methylated cyclodextrin soluble complexes of phthalimido-ferrocidiphenol for the first time.

AaTX1, from Androctonus australis scorpion venom: purification, synthesis and characterization in dopaminergic neurons.

We have purified the AaTX1 peptide from the Androctonus australis (Aa) scorpion venom, previously cloned and sequenced by Legros and collaborators in a venom gland cDNA library from Aa scorpion. AaTX1 belongs to the α-Ktx15 scorpion toxins family (αKTx15-4). Characterized members of this family share high sequence similarity and were found to block preferentially IA-type voltage-dependent K(+) currents in rat cerebellum granular cells in an irreversible way.

PIVL, a snake venom Kunitz-type serine protease inhibitor, inhibits in vitro and in vivo angiogenesis.

Development and homeostasis of the vascular system requires integrin-promoting endothelial cell adhesion, migration and survival. Nowadays, integrins represent potential targets for pharmacological agents and open new avenues for the control of metastatic spread in the treatment of tumor malignancies. We have already reported that PIVL, a serine protease inhibitor isolated from Macrovipera lebetina venom, displays an anti-tumor effect through interference with integrin receptor function.

Lebecin, a new C-type lectin like protein from Macrovipera lebetina venom with anti-tumor activity against the breast cancer cell line MDA-MB231.

C-type lectins like proteins display various biological activities and are known to affect especially platelet aggregation. Few of them have been reported to have anti-tumor effects. In this study, we have identified and characterized a new C-type lectin like protein, named lebecin.

Subtype-selective activation of K(v)7 channels by AaTXKβ₂₋₆₄, a novel toxin variant from the Androctonus australis scorpion venom.

K(v)7.4 channel subunits are expressed in central auditory pathways and in inner ear sensory hair cells and skeletal and smooth muscle cells. Openers of K(v)7.

Inhibition of human Kv3.1 current expressed in Xenopus oocytes by the toxic venom fraction of Androctonus australis hector.

AahG50, the toxic fraction of Androctonus australis hector venom, was studied on human Kv3.1 channels activation, stably expressed in Xenopus oocytes using the two-electrode voltage clamp technique. AahG50 reduced Kv3.

The pathological effects of Heminecrolysin, a dermonecrotic toxin from Hemiscorpius lepturus scorpion venom are mediated through its lysophospholipase D activity.

We have previously identified Heminecrolysin, a sphingomyelinase D (SMaseD), as the major protein responsible for the main pathological effects observed following Hemiscorpius (H.) lepturus scorpion envenomation. We aimed herein to further investigate the kinetics and molecular mechanisms triggered by Heminecrolysin to initiate hematological disorders and inflammatory reaction.

Antitumoral potential of Tunisian snake venoms secreted phospholipases A2.

Phospholipases type A2 (PLA2s) are the most abundant proteins found in Viperidae snake venom. They are quite fascinating from both a biological and structural point of view. Despite similarity in their structures and common catalytic properties, they exhibit a wide spectrum of pharmacological activities.

PIVL, a new serine protease inhibitor from Macrovipera lebetina transmediterranea venom, impairs motility of human glioblastoma cells.

A novel Kunitz-type serine proteinase inhibitor, termed PIVL, was purified to homogeneity from the venom of the Tunisian snake Macrovipera lebetina transmediterranea. It is a monomeric polypeptide chain cross-linked by three disulfide linkages with an isotope-averaged molecular mass of 7691.7 Da.

Pre-clinical studies of toxin-specific nanobodies: evidence of in vivo efficacy to prevent fatal disturbances provoked by scorpion envenoming.

Scorpions represent a significant threat to humans and animals in various countries throughout the world. Recently, we introduced Nanobodies (Nbs) to combat more efficiently scorpion envenoming and demonstrated the performance of NbAahIF12 and NbAahII10 to neutralize scorpion toxins of Androctonus australis hector venom. A bispecific Nb construct (NbF12-10) comprising these two Nbs is far more protective than the classic Fab'(2) based therapy and is the most efficient antivenom therapy against scorpion sting in preclinical studies.