A broadband method for measuring the complex permeability of thin magnetic films using a short-circuited microstrip fixture is presented. The method is based on full one-port offset-short calibration implemented directly in the fixture with a movable shorting wall, reducing sensitivity to coaxial-to-strip transition imperfections and eliminating the need for its precise optimization. Field-dependent normalization to the empty fixture reduces systematic errors from the external magnetic field, and a correction for residual saturated permeability improves retrieval accuracy. The method was validated on Co, supermalloy, and FeCo films on flexible PET substrates. Retrieved spectra agreed well with reference coaxial data and with the spectrum reconstructed from static magnetic measurements. In the present implementation, broadband spectra were obtained from 0.1 to 20 GHz with no significant systematic distortion, indicating that the proposed approach is suitable for accurate broadband characterization of thin magnetic films without reference standards or precise optimization of the coaxial-to-strip transition.

Snake venom vascular endothelial growth factors (svVEGFs) are homodimeric proteins comprising two equal subunits bound by two intermolecular disulfide bonds. The main biological effects of svVEGFs are local vasodilatation, increasing of vascular permeability, and hypotension. Barietin, a svVEGF purified from the venom of puff adder Bitis arietans, differs from other representatives of this toxin family by its shortened C-terminal amino acid sequence. No data about barietin effects on hemodynamics are available. Studying those in rats we found that barietin at a dose of 1 mg/kg significantly increased heart rate, exerting only a minor influence on blood pressure. In this respect, it differs from other svVEGFs having a significant effect on blood pressure. We aimed to find the barietin active fragment which may be responsible for its tachycardic activity. Because in literature the fragments corresponding to the so-called loop 1 of VEGF-A (a mammalian homologue of barietin) manifested some affinity to VEGF receptors, we synthesized a peptide homologous to this loop comprising barietin fragment 24-36, with two Cys residues added at the N- and C-termini to form a disulfide. At intravenous injection at a dose of 5 mg/kg, it showed a tendency to increase heart rate without any significant effect on blood pressure, thus demonstrated a trend to reproduce the effect of barietin. So, barietin is the first svVEGF which increases the heart rate without substantial effect on the blood pressure, with its fragment demonstrating a trend for a similar activity.

Microwave permeability of amorphous Co67Fe7B26 films deposited on a flexible substrate was studied in a wide range of film thicknesses up to 1.40 μm. Microwave permeability measurements were carried out using the coaxial technique in the frequency range from 0.1 to 10 GHz. It was found that both the static permeability and the ferromagnetic resonance frequency depend weakly on the film thickness. Analysis of the microwave data showed that the studied films possess in-plane magnetic anisotropy. The influence of the skin effect on the frequency dependence of the microwave permeability was modeled using an analytical approach. It was demonstrated that the decrease in the peak of the imaginary part of the microwave permeability with film thickness growth is related to the skin effect. The results obtained may be useful for microwave applications of soft magnetic CoFeB films.

Three-finger toxins (TFTs), including neurotoxins and cytotoxins, form one of the largest families of snake venom proteins and interact with various biological targets. Neurotoxins target proteinaceous receptors while cytotoxins interact mainly with the lipids of cell membranes and to a lesser extent with carbohydrates. However, no data about the interaction of TFTs with nucleic acids can be found. To detect this interaction, we applied spectrophotometry, ion-paired HPLC and electrophoretic mobility shift assay (EMSA). Using spectrophotometry, we found that TFTs from cobra venom increased the optical density of an RNA solution in a time-dependent manner indicating toxin interaction with RNA. A decrease in the net negative charge of the RNA molecule upon interaction with neurotoxin II from cobra venom was revealed by ion-pair HPLC. EMSA showed decreased electrophoretic mobility of both RNA and DNA upon addition of different TFTs including the non-conventional cobra toxin WTX and water-soluble recombinant human three-finger protein lynx1. We suggest that the interaction with nucleic acids may be a common property of TFTs, and some biological effects of TFTs, for example, cytotoxin-induced apoptosis in cancer cell lines, may be mediated by interaction with nucleic acids.

One of the main targets for snake venoms in animal and human organisms is the circulatory system. Mechanisms of circulatory system injury within the victim’s body include, among others, the direct effect of snake toxins on structures in blood vessel walls. The interaction of a toxin with cells and the extracellular matrix of the vessel wall may manifest as cytotoxicity, leading to cell death by necrosis or apoptosis, and damage to vascular wall structures. Such interactions may increase capillary permeability, promoting hemorrhage or edema, and may also induce alterations in vascular tone, resulting in changes in blood pressure. Snake toxins may also affect the growth, function, and regenerative ability of the endothelium, thus modulating angiogenesis; some toxins exert protective or anti-atherosclerotic effects. Toxins interacting with the vasculature may be classified as enzymes (phospholipases A2, metalloproteinases, L-amino acid oxidases, and hyaluronidases), proteins without enzymatic activity (vascular endothelial growth factors, disintegrins, C-type lectins and snaclecs, three-finger toxins, etc.), peptides (bradykinin-potentiating peptides, natriuretic peptides, sarafotoxins), and low-molecular-weight substances. This review summarizes the data on the vascular effects, particularly on the blood vessel wall, exhibited by various classes and groups of snake toxins.

Previously, we found that the venom of the pit viper Gloydius saxatilis inhibited the muscle-type nicotinic acetylcholine receptor (nAChR). Using liquid chromatography, a protein glosaxin was isolated from the venom that inhibited the binding of the α-bungarotoxin to the nAChR of muscle type from Torpedo californica. The amino acid sequence of the isolated protein was analyzed by high resolution mass spectrometry. Subsequent bioinformatic analysis showed that it is homologous to the amino acid sequences of disintegrin-like proteins, consisting of non-catalytic domains of type PIII metalloproteinases from the venom of pit vipers of genus Gloydius. A study of the biological activity of the isolated protein showed that it inhibits the binding of α-bungarotoxin to Torpedo californica nAChR with IC50 = 51 μM. The protein also inhibited acetylcholine-induced functional responses of the human neuronal nAChR of α3β2 subtype. This is the first evidence of the ability of proteins consisting of non-catalytic domains of snake venom type PIII metalloproteinase to inhibit the nAChR.

Bài báo này tiến hành đánh giá hoạt tính kháng viêm và kháng động vật nguyên sinh của cao chiết ethanol 30%, ethanol 96% và 1 số chất phân lập được từ toàn cây cam thảo nam thu hái tại Vĩnh Long. Kết quả cho thấy, cao ethanol 96% ức chế sản sinh nitric oxide ở nồng độ dưới 100μg/ml trên mô hình tế bào RAW264.7 gây viêm bởi LPS. Trên mô hình thực nghiệm gây viêm cấp tính bằng carrageenan 1% ở chuột nhắt trắng, lô điều trị bằng cao chiết 96% liều 500 mg/kg có độ sưng phù thấp hơn (chưa có ý nghĩa thống kê) so với lô chứng bệnh ở tất cả các thời điểm khảo sát. Lô điều trị bằng cao chiết 30% liều 500 mg/kg có có độ sưng phù thấp hơn (có ý nghĩa thống kê) so với lô chứng bệnh ở các thời điểm 1 giờ, 5 giờ và 24 giờ. So với lô chứng dương (điều trị bằng diclofenac liều 5mg/kg), chuột được điều trị với cao chiết 30%, liều 500 mg/kg có độ sưng phù khác biệt không có ý nghĩa thống kê so với lô chứng dương ở hầu hết các thời điểm khảo sát (V1, V3, V5). Những kết quả trên cho thấy cao chiết với ethanol 30% có tác động kháng viêm tốt hơn cao ethanol 96%, sau 24 giờ khảo sát. Ngoài ra, cao ethanol 30 % và ethanol 96% có tác động kháng động vật nguyên sinh Tetrahymena pyriformis sau 24 giờ ủ với cao chiết ở nồng độ 25 mg/ml. Sử dụng các phương pháp sắc ký, đã phân lập và xác định cấu trúc 5 hợp chất từ cao ethanol 96% (1-5), thử nghiệm chống động vật nguyên sinh với 3 chất (1-3) cho thấy cả 3 chất đều có hoạt tính chống động vật nguyên sinh ở mức trung bình.

Objective: Although main components of the venoms from Viperidae snakes are hemotoxins, several studies indicate the presence of neurotoxins in these venoms. We previously found that the venom of pit viper Gloydius saxatilis inhibited the muscle-type nicotinic acetylcholine receptor (nAChR). The objective of present work is to isolate and characterize a neurotoxic protein from this venom. Methods: The protein was isolated by liquid chromatography and characterized using high resolution mass-spectrometry. Results and Discussion: The isolated protein called glosaxin inhibited the binding of the α-bungarotoxin to the nAChR of muscle type from Torpedo californica. Investigation of the amino acid sequence of the isolated protein by high resolution mass spectrometry and the subsequent bioinformatic analysis showed that it is homologous to the amino acid sequences of disintegrin-like proteins, consisting of non-catalytic domains of class PIII metalloproteinases from the venom of pit vipers of genus Gloydius. Glosaxin was shown to inhibit the binding of α-bungarotoxin to T. californica nAChR with IC50 = 51 μM. It also inhibited ACh-induced functional responses of the human neuronal nAChR of α3β2 subtype. Conclusions: This is the first evidence for the ability of proteins consisting of non-catalytic domains of snake venom class PIII metalloproteinase to inhibit the nAChR.

Changes in the microwave permeability of permalloy films with an increase in the film thickness are studied. Measurement data on the evolution of microwave permeability with film thickness are analyzed in the framework of a model for the film with a regular stripe domain structure and out-of-plane magnetic anisotropy. A correlation between the microwave magnetic properties and magnetic structure of permalloy films is established. It is demonstrated that the observed decrease in the ferromagnetic resonance frequency and the static permeability with a growth in the film thickness can ascribed to the appearance of perpendicular anisotropy and the formation of a stripe domain structure. The calculated dependences of the ferromagnetic resonance frequency and static permeability on the film thickness are in reasonable agreement with the measurement results. Based on the analysis of these dependences, the domain width in the permalloy films is estimated. It is found that for thick permalloy films, the domain width is of the order of the film thickness. The results obtained may be useful for high-frequency applications of soft magnetic films.

The effects of extracts of ten plant species from Russia and five species from Vietnam on the growth and survival of ciliates Tetrahymena pyriformis were studied. T. pyriformis belongs to the subkingdom Protozoa, which also includes pathogens of protozoan infections. Extraction of dried plants was carried out with acidic and alkaline aqueous solutions, as well as with an aqueous ethanol. Various amounts of extracts were added to the ciliate cells, and the number of cells survived after incubation for 1 and 24 h was recorded. We found that our samples of several plants, including wormwood, harmala, and licorice, similarly to those studied earlier, exhibit antiprotozoal activity, which may indicate that the secondary metabolites are the same in plants from different regions. Using the ciliate T. pyriformis as a model organism, the presence of antiprotozoal activity in extracts of lilac, chondrilla, cinquefoil, hop, and elm was shown for the first time.

— Many different receptors and ion channels that regulate ion currents are involved in the control of the cardiovascular system (CVS). The functioning of the CVS occurs with the involvement of the processes of nervous and humoral regulation; in both cases, acetylcholine receptors of different families and subtypes as well as of different localization take part in these processes. It was demonstrated that acetylcholine receptors are directly located on the cell membranes of the heart and blood vessels; and this review considers the regulation of CVS functions with the involvement of only those acetylcholine receptors that are located in the tissue of the heart and blood vessels. In general, both muscarinic and nicotinic acetylcholine receptors are widely present in the tissues of the CVS. At the same time, muscarinic acetylcholine receptors are generally involved in the regulation of vascular tone and contractility of the heart, while nicotinic acetylcholine receptors are mainly involved in the regulation of a number of important pathophysiological processes directly affecting the functioning of the CVS. The regulation of the functioning of acetylcholine receptors can be considered as an addition to the existing methods of treating CVS diseases, including such diseases as atherosclerosis and heart failure. The use of blockers and activators of acetylcholine receptors for the study and/or treatment of pathological conditions of CVS is discussed.

The relationship between the chemical purity of one-size particles and microwave properties in ferromagnetic materials is not clearly studied. Ferromagnetic nanostructured iron powders were synthesized from iron nitrate solution using ultrasonic spray-pyrolysis and then reduced in H2 flow at 350, 400, 450, and 500 °C. A rise in the concentration of solutions of a precursor from 10 to 20 wt. % led to an increase in mean particle size. The interrelationship was studied between chemical composition and the microwave dispersion of the powders obtained. An increase in the temperature of reduction changes the chemical composition and increases the amplitude of complex microwave permeability, which was studied using solid-state physics methods (XRD, STA, SEM, and VNA). It was found that annealing at 400 °C is the optimal treatment that allows the production of iron powders, consisting of about 90% of α-Fe phase, possessing a particle surface with low roughness and porosity, and demonstrating intense microwave absorption. Annealing at a higher temperature (500 °C) causes an even higher increase in permeability but leads to the destruction of nanostructured spheres into smaller particles due to grain growth. This destruction causes an abrupt increase in permittivity and therefore significantly reduces potential applications of the product. The insight into chemical–magnetic relationships of these materials enhances the data for design applications in magnetic field sensing.

Snake venoms as tools for hunting are primarily aimed at the most vital systems of the prey, especially the nervous and circulatory systems. In general, snakes of the Elapidae family produce neurotoxic venoms comprising of toxins targeting the nervous system, while snakes of the Viperidae family and most rear-fanged snakes produce hemotoxic venoms directed mainly on blood coagulation. However, it is not all so clear. Some bites by viperids results in neurotoxic signs and it is now known that hemotoxic venoms do contain neurotoxic components. For example, viperid phospholipases A2 may manifest pre- or/and postsynaptic activity and be involved in pain and analgesia. There are other neurotoxins belonging to diverse families ranging from large multi-subunit proteins (e.g., C-type lectin-like proteins) to short peptide neurotoxins (e.g., waglerins and azemiopsin), which are found in hemotoxic venoms. Other neurotoxins from hemotoxic venoms include baptides, crotamine, cysteine-rich secretory proteins, Kunitz-type protease inhibitors, sarafotoxins and three-finger toxins. Some of these toxins exhibit postsynaptic activity, while others affect the functioning of voltage-dependent ion channels. This review represents the first attempt to systematize data on the neurotoxins from “non-neurotoxic” snake venom. The structural and functional characteristic of these neurotoxins affecting diverse targets in the nervous system are considered.

Protozoal infections are a world-wide problem. The toxicity and somewhat low effectiveness of the existing drugs require the search for new ways of protozoa suppression. Snake venom contains structurally diverse components manifesting antiprotozoal activity; for example, those in cobra venom are cytotoxins. In this work, we aimed to characterize a novel antiprotozoal component(s) in the Bungarus multicinctus krait venom using the ciliate Tetrahymena pyriformis as a model organism. To determine the toxicity of the substances under study, surviving ciliates were registered automatically by an original BioLaT-3.2 instrument. The krait venom was separated by three-step liquid chromatography and the toxicity of the obtained fractions against T. pyriformis was analyzed. As a result, 21 kDa protein toxic to Tetrahymena was isolated and its amino acid sequence was determined by MALDI TOF MS and high-resolution mass spectrometry. It was found that antiprotozoal activity was manifested by β-bungarotoxin (β-Bgt) differing from the known toxins by two amino acid residues. Inactivation of β-Bgt phospholipolytic activity with p-bromophenacyl bromide did not change its antiprotozoal activity. Thus, this is the first demonstration of the antiprotozoal activity of β-Bgt, which is shown to be independent of its phospholipolytic activity.

Since the beginning of the HIV epidemic, lasting more than 30 years, the main goal of scientists was to develop effective methods for the prevention and treatment of HIV infection. Modern medicines have reduced the death rate from AIDS by 80%. However, they still have side effects and are very expensive, dictating the need to search for new drugs. Earlier, it was shown that phospholipases A2 (PLA2s) from bee and snake venoms block HIV replication, the effect being independent on catalytic PLA2 activity. However, the antiviral activity of human PLA2s against Lentiviruses depended on catalytic function and was mediated through the destruction of the viral membrane. To clarify the role of phospholipolytic activity in antiviral effects, we analyzed the anti-HIV activity of several snake PLA2s and found that the mechanisms of their antiviral activity were similar to that of mammalian PLA2. Our results indicate that snake PLA2s are capable of inhibiting syncytium formation between chronically HIV-infected cells and healthy CD4-positive cells and block HIV binding to cells. However, only dimeric PLA2s had pronounced virucidal and anti-HIV activity, which depended on their catalytic activity. The ability of snake PLA2s to inactivate the virus may provide an additional barrier to HIV infection. Thus, snake PLA2s might be considered as candidates for lead molecules in anti-HIV drug development.

To search for compounds with antiprotozoal activity, effects of snake venoms on the ciliates Tetrahymena pyriformis was studied. T. pyriformis from subkingdom of Protozoa, including the protozoal pathogens, was used as a model organism to select the venoms that are the most active against parasitic protozoans. Various concentrations of venoms were added to the cells, and the cells that survived after 24 h were counted. Among the six snake species from the Viperidae family, the venom of the viper Vipera berus, which completely killed the cells at 49 μg/mL, was the most active. Among four species from the Elapidae family, the previously studied cobra venoms containing cytotoxins with strong antiprotozoal activity as well as the venom of krait Bungarus multicinctus (10 μg/mL) were the most active. The venoms of the pit vipers and Nikolsky's viper did not show any activity at 12.5 mg/mL. Thus, the venoms of V. berus and B. multicinctus are promising for the isolation of new antiprotozoal compounds.

Hollow ferromagnetic powders of iron were obtained by means of ultrasonic spray pyrolysis. A variation in the conditions of the synthesis allows for the adjustment of the mean size of the hollow iron particles. Iron powders were obtained by this technique, starting from the aqueous solution of iron nitrate of two different concentrations: 10 and 20 wt.%. This was followed by a reduction in hydrogen. An increase in the concentration of the solution increased the mean particle size from 0.6 to 1.0 microns and widened particle size distribution, but still produced hollow particles. Larger particles appeared problematic for the reduction, although admixture of iron oxides did not decrease the microwave permeability of the material. The paraffin wax-based composites filled with obtained powders demonstrated broadband magnetic loss with a complex structure for lesser particles, and single-peak absorption for particles of 1 micron. Potential applications are 5G technology, electromagnetic compatibility designs, and magnetic field sensing.

A new coronavirus was recently discovered and named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In the absence of specific therapeutic and prophylactic agents, the virus has infected almost hundred million people, of whom nearly two million have died from the viral disease COVID-19. The ongoing COVID-19 pandemic is a global threat requiring new therapeutic strategies. Among them, antiviral studies based on natural molecules are a promising approach. The superfamily of phospholipases A2 (PLA2s) consists of a large number of members that catalyze the hydrolysis of phospholipids at a specific position. Here we show that secreted PLA2s from the venom of various snakes protect to varying degrees the Vero E6 cells widely used for the replication of viruses with evident cytopathic action, from SARS-CoV-2 infection PLA2s showed low cytotoxicity to Vero E6 cells and the high antiviral activity against SARS-CoV-2 with IC 50 values ranged from 0.06 to 7.71 μg/ml. Dimeric PLA2 HDP-2 from the viper Vipera nikolskii , as well as its catalytic and inhibitory subunits, had potent virucidal (neutralizing) activity against SARS-CoV-2. Inactivation of the enzymatic activity of the catalytic subunit of dimeric PLA2 led to a significant decrease in antiviral activity. In addition, dimeric PLA2 inhibited cell-cell fusion mediated by SARS-CoV-2 spike glycoprotein. These results suggest that snake PLA2s, in particular dimeric ones, are promising candidates for the development of antiviral drugs that target lipid bilayers of the viral envelope and may be good tools to study the interaction of viruses with host cell membranes.

Protective SiO2 coating deposited to iron microparticles is highly demanded both for the chemical and magnetic performance of the latter. Hydrolysis of tetraethoxysilane is the crucial method for SiO2 deposition from a solution. The capabilities of this technique have not been thoroughly studied yet. Here, two factors were tested to affect the chemical composition and the thickness of the SiO2 shell. It was found that an increase in the hydrolysis reaction time thickened the SiO2 shell from 100 to 200 nm. Moreover, a decrease in the acidity of the reaction mixture not only thickened the shell but also varied the chemical composition from SiO3.0 to SiO8.6. The thickness and composition of the dielectric layer were studied by scanning electron microscopy and energy-dispersive X-ray analysis. Microwave permeability and permittivity of the SiO2-coated iron particles mixed with a paraffin wax matrix were measured by the coaxial line technique. An increase in thickness of the silica layer decreased the real quasi-static permittivity. The changes observed were shown to agree with the Maxwell Garnett effective medium theory. The new method developed to fine-tune the chemical properties of the protective SiO2 shell may be helpful for new magnetic biosensor designs as it allows for biocompatibility adjustment.

Among the brain tumors, glioma is the most common. In general, different biochemical mechanisms, involving nicotinic acetylcholine receptors (nAChRs) and the arachidonic acid cascade are involved in oncogenesis. Although the engagement of the latter in survival and proliferation of rat C6 glioma has been shown, there are practically no data about the presence and the role of nAChRs in C6 cells. In this work we studied the effects of nAChR antagonists, marine snail α-conotoxins and snake α-cobratoxin, on the survival and proliferation of C6 glioma cells. The effects of the lipoxygenase and cyclooxygenase inhibitors either alone or together with α-conotoxins and α-cobratoxin were studied in parallel. It was found that α-conotoxins and α-cobratoxin promoted the proliferation of C6 glioma cells, while nicotine had practically no effect at concentrations below 1 µL/mL. Nordihydroguaiaretic acid, a nonspecific lipoxygenase inhibitor, and baicalein, a 12-lipoxygenase inhibitor, exerted antiproliferative and cytotoxic effects on C6 cells. nAChR inhibitors weaken this effect after 24 h cultivation but produced no effects at longer times. Quantitative real-time polymerase chain reaction showed that mRNA for α4, α7, β2 and β4 subunits of nAChR were expressed in C6 glioma cells. This is the first indication for involvement of nAChRs in mechanisms of glioma cell proliferation.