Specific Complex Research Articles

First Episode Psychosis and Schizophrenia Are Systemic Neuro-Immune Disorders Triggered by a Biotic Stimulus in Individuals with Reduced Immune Regulation and Neuroprotection.

There is evidence that schizophrenia is characterized by activation of the immune-inflammatory response (IRS) and compensatory immune-regulatory systems (CIRS) and lowered neuroprotection. Studies performed on antipsychotic-naïve first episode psychosis (AN-FEP) and schizophrenia (FES) patients are important as they may disclose the pathogenesis of FES. However, the protein–protein interaction (PPI) network of FEP/FES is not established. The aim of the current study was to delineate a) the characteristics of the PPI network of AN-FEP and its transition to FES; and b) the biological functions, pathways, and molecular patterns, which are over-represented in FEP/FES. Toward this end, we used PPI network, enrichment, and annotation analyses. FEP and FEP/FES are strongly associated with a response to a bacterium, alterations in Toll-Like Receptor-4 and nuclear factor-κB signaling, and the Janus kinases/signal transducer and activator of the transcription proteins pathway. Specific molecular complexes of the peripheral immune response are associated with microglial activation, neuroinflammation, and gliogenesis. FEP/FES is accompanied by lowered protection against inflammation, in part attributable to dysfunctional miRNA maturation, deficits in neurotrophin and Wnt/catenin signaling, and adherens junction organization. Multiple interactions between reduced brain derived neurotrophic factor, E-cadherin, and β-catenin and disrupted schizophrenia-1 (DISC1) expression increase the vulnerability to the neurotoxic effects of immune molecules, including cytokines and complement factors. In summary: FEP and FES are systemic neuro-immune disorders that are probably triggered by a bacterial stimulus which induces neuro-immune toxicity cascades that are overexpressed in people with reduced anti-inflammatory and miRNA protections, cell–cell junction organization, and neurotrophin and Wnt/catenin signaling.

On the conservation of fungi

The article is devoted to the actual problem of conservation of biological diversity in the modern world. The basic principles and specific approaches to the protection of macromycetes as organisms that are difficult in qualitative and quantitative accounting due to the peculiarities of biology and life cycle have been studied. Domestic and global trends and practices in the field of protecting the species diversity of agaricoid fungi as a component of any ecosystem are discussed. The information on the features of regional fungal diversity detection, rare and threatened species for inclusion into the Red lists of various levels as well as on determining the boundaries of fungal populations, including using barcoding methods is provided. It is noted that for the organization of specially protected natural areas, it is necessary to specify and substantiate the changes in the status of separate species, to identify key areas with specific and typical mycological complexes. The idea that the system of mushroom protection should be integrated into the general system of nature protection is substantiated. Along with the protection of rare and endangered fungi species in their typical habitats (nature reserves, nature parks, wildlife areas, etc.), priority directions for preserving the gene pool of fungi in scientific collections and ex situ banks are described. Live mycelial cultures of fungi can be used for the development of new resistant populations by the reintroduction of rare and endangered species, as well as for the production of fungal metabolites useful for humans. There has been also discussed the problem of improving the effectiveness of protective measures through the digitalization of information systems: free and open access to the data on the endangered fungi species through the development of specialized computer databases, websites and unified information banks.

Synthesis, characterization, design, molecular docking, anti COVID-19 activity, DFT calculations of novel Schiff base with some transition metal complexes

The elemental analyses, infrared, magnetic measures, UV–Visible, 1H NMR, 13C NMR, and XRD analysis were used to study Co(II), Ni(II), and Cu(II) metal complexes (1–3) with a novel Schiff base (HL). The ligand performances as a mononegative tridentate NNO, according to the spectrum data. In Co(II), Ni(II), and Cu(II) metal complexes, an octahedral structure has been proposed based on magnetic and electronic spectrum data. The thermodynamic properties of the ligand and its complexes are measured via the Coats-Redfern and Horowitz-Metzger procedures. The bond angles, the bond lengths, and quantum chemical factors are shown in the molecular modeling using the DFT approach. The ligand and its complexes have been studied via absorption spectra studies in calf thymus DNA binding and also viscosity calf thymus DNA binding studies. Utilizing o-aminophenol such as a reference material catalyzed by metal complexes, dioxygen stimulation in parameters of phenoxazinone synthase activity is comprehensively examined. By interacting by SARS-CoV-2 main protease, which was obtained from the RCSB pdb database PDB ID: 6 W41, to anticipate the action of HL in contradiction of COVID-19 and its anticancer properties with cancer of prostate protein 3qum, the docking binding sites contacts were evaluated. As a result, future research and clinical studies into HL as a potential COVID-19 illness and prostate cancer therapy drug induced. Vinblastine and colchicine viability tests were used to compare the outcomes of the complexes targeting human tumor cell lines MCF-7 and HepG-2. All complexes' in vitro antioxidant properties were measured by DPPH free radical scavenger tests. Additionally, antibacterial action of the ligand and specific complexes was investigated in vitro in contradiction of Gram + ve bacteria (Staphylococcus aureus) and Gram-ve bacteria Escherichia coli (E. coli) utilizing inhibition zone diameter.

Proximity-dependent biotinylation approaches to study apicomplexan biology.

In the last 10years, proximity-dependent biotinylation (PDB) techniques greatly expanded the ability to study protein environments in the living cell that range from specific protein complexes to entire compartments. This is achieved by using enzymes such as BirA* and APEX that are fused to proteins of interest and biotinylate proteins in their proximity. PDB techniques are now also increasingly used in apicomplexan parasites. In this review, we first give an overview of the main PDB approaches and how they compare with other techniques that address similar questions. PDB is particularly valuable to detect weak or transient protein associations under physiological conditions and to study cellular structures that are difficult to purify or have a poorly understood protein composition. We also highlight new developments such as novel smaller or faster-acting enzyme variants and conditional PDB approaches, providing improvements in both temporal and spatial resolution which may offer broader application possibilities useful in apicomplexan research. In the second part, we review work using PDB techniques in apicomplexan parasites and how this expanded our knowledge about these medically important parasites.

Splenomegaly development and disseminated intravascular coagulation syndrome in acute canine babesiosis

Disseminated intravascular coagulation (DIC) syndrome is the main defining process in the pathogenetic axis of complications in canine babesiosis. The involvement of the spleen with further irreversible changes in the organ largely determines the severity of the animal’s condition after spontaneous babesiosis. The work presented here aimed to determine the role of the DIC syndrome as a triggering factor for lesions of the spleen. Clinical and laboratory studies (haematological, biochemical, hemodynamic) have been carried out. Pathological studies of the removed spleen were carried out by histological methods using universal and specific staining. After suffering acute spontaneous babesiosis, the development of hypersplenism and splenomegaly was found in dogs. The diagnosis was confirmed haematologically by the detected cytopenia, normochromic type anaemia. An additional parameter was a significantly increased erythrocyte sedimentation rate. The biochemical profile indicated the development of bilirubinaemia due to the conjugated fraction, hyperfermentation of transaminases, hypoalbuminemia, which reflected the development of hepatitis and liver failure. Markers of DIC syndrome in laboratory studies are represented by reliable hypofibrinogenemia, increased level of fibrinogen/fibrin degradation products, including D-dimer, and soluble fibrin monomer complexes. The multidirectional indices of coagulation tests (activated partial thromboplastin and prothrombin time) made it possible to classify the stage of “consumption coagulopathy” of the DIC syndrome. The haemodynamic parameters of the sick dogs were characterized by a significant deficit in the circulating blood volume. Together with the indicators of the “consumption coagulopathy” stage of the DIC syndrome, the hemodynamic indexes indicate a moderate degree of shock stage II – the stable reversibility, but the magnitude of the circulating blood volume deficit determines the tendency towards shock irreversibility. Histological studies have established a significant proliferation of the stromal elements of the organ, the formation of specific complexes of vessels with sinuses, clogging with blood clots, and the organ's parenchyma dystrophy. Such changes characterize complete splenomegaly, which is based on the organo-pathology of the DIC syndrome. The deposition of “old” fibrin in the connective tissue structures of the spleen indicates that DIC syndrome continues throughout the entire period of hyperplastic changes in the organ. The presence of hyalinosis in blood vessel walls of the spleen parenchyma determines irreversible changes in them. Thus, DIC syndrome is the basis for splenomegaly development in dogs after acute spontaneous babesiosis. It is confirmed by laboratory blood tests and histologically by the presence of fibrin thrombi in the structures of the organ, which determine the organopathology of the syndrome. The information obtained serves to expand the concepts of the pathogenesis of blood protozoal disease, define the high risk of complications that can become fatal for the health and life of animals.

Transsynaptic N-Cadherin Adhesion Complexes Control Presynaptic Vesicle and Bulk Endocytosis at Physiological Temperature.

At mammalian glutamatergic synapses, most basic elements of synaptic transmission have been shown to be modulated by specific transsynaptic adhesion complexes. However, although crucial for synapse homeostasis, a physiological regulation of synaptic vesicle endocytosis by adhesion molecules has not been firmly established. The homophilic adhesion protein N-cadherin is localized at the peri-active zone, where the highly temperature-dependent endocytosis of vesicles occurs. Here, we demonstrate an important modulatory role of N-cadherin in endocytosis at near physiological temperature by synaptophysin-pHluorin imaging. Different modes of endocytosis including bulk endocytosis were dependent on N-cadherin expression and function. N-cadherin modulation might be mediated by actin filaments because actin polymerization ameliorated the knockout-induced endocytosis defect. Using super-resolution imaging, we found strong recruitment of N-cadherin to glutamatergic synapses upon massive vesicle release, which might in turn enhance vesicle endocytosis. This provides a novel, adhesion protein-mediated mechanism for efficient coupling of exo- and endocytosis.

Interaction of Male Specific Lethal complex and genomic imbalance on global gene expression in Drosophila

The inverse dosage effect caused by chromosome number variations shows global consequences in genomic imbalance including sexual dimorphism and an X chromosome-specific response. To investigate the relationship of the MSL complex to genomic imbalance, we over-expressed MSL2 in autosomal and sex chromosomal aneuploids, and analyzed the different transcriptomes. Some candidate genes involved in regulatory mechanisms have also been tested during embryogenesis using TSA-FISH. Here we show that the de novo MSL complex assembled on the X chromosomes in females further reduced the global expression level on the basis of 2/3 down-regulation caused by the inverse dosage effect in trisomy through epigenetic modulations rather than induced dosage compensation. Plus, the sexual dimorphism effect in unbalanced genomes was further examined due to the pre-existing of the MSL complex in males. All these results demonstrate the dynamic functions of the MSL complex on global gene expression in different aneuploid genomes.

Means of Semantic Compression in Modern English Scientific Discourse (Based on Abstracts to the Articles From International Scientific Citation Databases)

The article explores the phenomenon of semantic compression in small format metatexts within the contemporary English scientific discourse. Abstracts to scientific articles from international citation databases, in particular those of Scopus and Web of Science, are analysed with the aim of eliciting ways of semantic compression. The latter is viewed as a key parameter of a scientific abstract, whose semantic quality is the main factor responsible for further integration of the research results into the global knowledge pool. It is presumed that an abstract, being a secondary small-format text, represents an exact semantic copy of the original scientific article, hence compression is viewed as a mechanism of redistributing the functional load of the eliminated units of the original by means of increasing the informative potential of the remaining elements within the secondary small-format text. In the process of pragma-semantic and discourse analysis, a specific complex of semantic compression methods is revealed on every level of scientific abstract organization; in particular, compression means are elicited on the structural and semantic textual levels, as well as on the morphological, lexical, syntactic and graphical ones. The revealed patterns, on the one hand, expand our understanding of compression mechanisms typical of small-format texts in general; on the other hand, the practical data obtained as a result of the analysis can be used by a wide range of researchers while writing abstracts in English for publications in high-ranking international scientific journals.

Advanced Sampling Methods for Multiscale Simulation of Disordered Proteins and Dynamic Interactions.

Intrinsically disordered proteins (IDPs) are highly prevalent and play important roles in biology and human diseases. It is now also recognized that many IDPs remain dynamic even in specific complexes and functional assemblies. Computer simulations are essential for deriving a molecular description of the disordered protein ensembles and dynamic interactions for a mechanistic understanding of IDPs in biology, diseases, and therapeutics. Here, we provide an in-depth review of recent advances in the multi-scale simulation of disordered protein states, with a particular emphasis on the development and application of advanced sampling techniques for studying IDPs. These techniques are critical for adequate sampling of the manifold functionally relevant conformational spaces of IDPs. Together with dramatically improved protein force fields, these advanced simulation approaches have achieved substantial success and demonstrated significant promise towards the quantitative and predictive modeling of IDPs and their dynamic interactions. We will also discuss important challenges remaining in the atomistic simulation of larger systems and how various coarse-grained approaches may help to bridge the remaining gaps in the accessible time- and length-scales of IDP simulations.

From development to application of an optimized gas chromatography analysis for C3-C10 hydrocarbons

Reducing the Gas Chromatography (GC) run time, and improving the resolution with appropriate peak heights in GC methods are indeed vital goals for any analysis labs. This research was focused on improving an existing empirical method for C3-C10 hydrocarbon analysis in a specific petrochemical complex with many samples per day. The hydrocarbon standards used for calibration were 0.5 W/W% Benzene and 0.5 W/W% 1-Methyl-Cyclopentene, as well as 2 W/W% m-Xylene and 2 W/W% p-Xylene. Moreover, Box-Behnken Design was used to identify the common significant variables between 11 quantitative input factors affecting the retention time, peak resolution and height for each pair. After performing 182 experimental analyses, carrier gas flow rate, initial temperature hold time, oven programming (ramp 1) and oven initial temperature were identified as the common significant variables. The results were used to optimize the method which could increase the resolutions by 50% and 40%, and simultaneously decrease the retention time by 34.2% and 28.3% for both pairs respectively.

Membrane-Bound Flavocytochrome MsrQ Is a Substrate of the Flavin Reductase Fre in Escherichia coli.

MsrPQ is a new type of methionine sulfoxide reductase (Msr) system found in bacteria. It is specifically involved in the repair of periplasmic methionine residues that are oxidized by hypochlorous acid. MsrP is a periplasmic molybdoenzyme that carries out the Msr activity, whereas MsrQ, an integral membrane-bound hemoprotein, acts as the physiological partner of MsrP to provide electrons for catalysis. Although MsrQ (YedZ) was associated since long with a protein superfamily named FRD (ferric reductase domain), including the eukaryotic NADPH oxidases and STEAP proteins, its biochemical properties are still sparsely documented. Here, we have investigated the cofactor content of the E. coli MsrQ and its mechanism of reduction by the flavin reductase Fre. We showed by electron paramagnetic resonance (EPR) spectroscopy that MsrQ contains a single highly anisotropic low-spin (HALS) b-type heme located on the periplasmic side of the membrane. We further demonstrated that MsrQ holds a flavin mononucleotide (FMN) cofactor that occupies the site where a second heme binds in other members of the FDR superfamily on the cytosolic side of the membrane. EPR spectroscopy indicates that the FMN cofactor can accommodate a radical semiquinone species. The cytosolic flavin reductase Fre was previously shown to reduce the MsrQ heme. Here, we demonstrated that Fre uses the FMN MsrQ cofactor as a substrate to catalyze the electron transfer from cytosolic NADH to the heme. Formation of a specific complex between MsrQ and Fre could favor this unprecedented mechanism, which most likely involves transfer of the reduced FMN cofactor from the Fre active site to MsrQ.

Dynamics in a phase model of half-center oscillator: Two neurons with excitatory coupling

A minimalistic model of the half-center oscillator is proposed. Within it, we consider dynamics of two excitable neurons interacting by means of the excitatory coupling. In the parameter space of the model, we identify the regions of dynamics, characteristic for central pattern generators: respectively, in-phase, anti-phase synchronous oscillations and quiescence, and study various bifurcation transitions between all these states. Suggested model can serve as a building block of specific complex central pattern generators for studies of rhythmic activity and information processing in animals and humans.

The mechanism of non-coding RNAs in medulloblastoma.

Medulloblastoma (MB) is one of the most common malignant tumors of the central nervous system in children. Although surgery, radiotherapy and chemotherapy have resulted in considerable progress in the treatment of this disease, the prognosis of patients with MB remains very poor. Therefore, highly specific molecular targeted treatment, which can improve the therapeutic efficacy and reduce the side effects of MB, has become a research hotspot. In recent years, non-coding RNAs (ncRNAs), which were initially considered to be transcriptional noise, have been shown to possess regulatory functions. A series of ncRNAs have been identified, including microRNAs and circular RNAs, which affect the expression of specific genes in a variety of tumors. These genes lead to the formation of a specific complex of proteins or they directly participate in protein synthesis in order to regulate the occurrence and development of tumors. The aim of the present review article was to summarize the recent research studies that have explored the ability of ncRNAs to regulate the occurrence and development of MB.

Deep Sequencing of MHC-Adapted Viral Lines Reveals Complex Recombinational Exchanges With Endogenous Retroviruses Leading to High-Frequency Variants.

Experimental evolution (serial passage) of Friend virus complex (FVC) in mice demonstrates phenotypic adaptation to specific host major histocompatibility complex (MHC) genotypes. These evolved viral lines show increased fitness and virulence in their host-genotype-of-passage, but display fitness and virulence tradeoffs when infecting unfamiliar host MHC genotypes. Here, we deep sequence these viral lines in an attempt to discover the genetic basis of FVC adaptation. The principal prediction for genotype-specific adaptation is that unique mutations would rise to high frequency in viral lines adapted to each host MHC genotype. This prediction was not supported by our sequencing data as most observed high-frequency variants were present in each of our independently evolved viral lines. However, using a multi-variate approach to measure divergence between viral populations, we show that populations of replicate evolved viral lines from the same MHC congenic mouse strain were more similar to one another than to lines derived from different MHC congenic mouse strains, suggesting that MHC genotype does predictably act on viral evolution in our model. Sequence analysis also revealed rampant recombination with endogenous murine leukemia virus sequences (EnMuLVs) that are encoded within the BALB/c mouse genome. The highest frequency variants in all six lines contained a 12 bp insertion from a recombinant EnMuLV source, suggesting such recombinants were either being favored by selection or were contained in a recombinational hotspot. Interestingly, they did not reach fixation, as if they are low fitness. The amount of background mutations linked to FVC/EnMuLV variable sites indicated that FVC/EnMuLV recombinants had not reached mutation selection equilibrium and thus, that EnMuLV sequences are likely continuously introgressing into the replicating viral population. These discoveries raise the question: is the expression of EnMuLV sequences in mouse splenocytes that permit recombination with exogenous FVC a pathogen or host adaptation?

Classification of protein\u2013protein association rates based on biophysical informatics

BackgroundProteins form various complexes to carry out their versatile functions in cells. The dynamic properties of protein complex formation are mainly characterized by the association rates which measures how fast these complexes can be formed. It was experimentally observed that the association rates span an extremely wide range with over ten orders of magnitudes. Identification of association rates within this spectrum for specific protein complexes is therefore essential for us to understand their functional roles.ResultsTo tackle this problem, we integrate physics-based coarse-grained simulations into a neural-network-based classification model to estimate the range of association rates for protein complexes in a large-scale benchmark set. The cross-validation results show that, when an optimal threshold was selected, we can reach the best performance with specificity, precision, sensitivity and overall accuracy all higher than 70%. The quality of our cross-validation data has also been testified by further statistical analysis. Additionally, given an independent testing set, we can successfully predict the group of association rates for eight protein complexes out of ten. Finally, the analysis of failed cases suggests the future implementation of conformational dynamics into simulation can further improve model.ConclusionsIn summary, this study demonstrated that a new modeling framework that combines biophysical simulations with bioinformatics approaches is able to identify protein–protein interactions with low association rates from those with higher association rates. This method thereby can serve as a useful addition to a collection of existing experimental approaches that measure biomolecular recognition.

Remdesivir interactions with sulphobutylether-β-cyclodextrins: A case study using selected substitution patterns

Modified cyclodextrins (CDs) consist of a distribution of different structures with different number and location of the substituted groups. Among the most important applications of these molecules is their use as an enabling excipient in pharmaceutical formulations to provide the necessary solubility, stability and bioavailability for a drug to be effectively used. The most typical interaction mechanism of small molecular groups with CDs is the formation of host–guest inclusion complexes. The thermodynamic affinity constant between CDs and drugs should not be too strong, since then the biological activity could be negated by the formation of the complex. In the opposite scenario, if the affinity constant is too weak, the complex is barely formed and the amount of CD required in the formulation may become too great. Thus, a balance between the affinity of the CD and the drug is necessary for an optimal formulation. Additionally in the case of modified CDs and specific drug complexes there are further questions concerning the effect that the locations and number of substitutions plays in complexation. In the present work, this question is explored by using sulphobutylether-β-cyclodextrin and remdesivir, the only antiviral medication currently approved by the United States Food and Drug Administration for treating COVID-19, as a case study. This paper presents results from an orthogonal study using isothermal titration calorimetry measurements and biased molecular dynamics simulations that provide complementary information. Isothermal titration calorimetry delves into the global impact of the species distribution while molecular dynamics simulations deals with specific chemical structures. The goal is to provide useful information to optimize pharmaceutical formulations based on modified CDs, specifically in the case of remdesivir, used to treat SARS-CoV-2 infection, although the main conclusions could be extended to the interaction of other drugs with modified cyclodextrins.

Autoantibody-Specific Signalling in Pemphigus.

Pemphigus is a severe autoimmune disease impairing barrier functions of epidermis and mucosa. Autoantibodies primarily target the desmosomal adhesion molecules desmoglein (Dsg) 1 and Dsg 3 and induce loss of desmosomal adhesion. Strikingly, autoantibody profiles in pemphigus correlate with clinical phenotypes. Mucosal-dominant pemphigus vulgaris (PV) is characterised by autoantibodies (PV-IgG) against Dsg3 whereas epidermal blistering in PV and pemphigus foliaceus (PF) is associated with autoantibodies against Dsg1. Therapy in pemphigus is evolving towards specific suppression of autoantibody formation and autoantibody depletion. Nevertheless, during the acute phase and relapses of the disease additional treatment options to stabilise desmosomes and thereby rescue keratinocyte adhesion would be beneficial. Therefore, the mechanisms by which autoantibodies interfere with adhesion of desmosomes need to be characterised in detail. Besides direct inhibition of Dsg adhesion, autoantibodies engage signalling pathways interfering with different steps of desmosome turn-over. With this respect, recent data indicate that autoantibodies induce separate signalling responses in keratinocytes via specific signalling complexes organised by Dsg1 and Dsg3 which transfer the signal of autoantibody binding into the cell. This hypothesis may also explain the different clinical pemphigus phenotypes.

Post-Translational Modification and Subcellular Compartmentalization: Emerging Concepts on the Regulation and Physiopathological Relevance of RhoGTPases.

Cells and tissues are continuously exposed to both chemical and physical stimuli and dynamically adapt and respond to this variety of external cues to ensure cellular homeostasis, regulated development and tissue-specific differentiation. Alterations of these pathways promote disease progression—a prominent example being cancer. Rho GTPases are key regulators of the remodeling of cytoskeleton and cell membranes and their coordination and integration with different biological processes, including cell polarization and motility, as well as other signaling networks such as growth signaling and proliferation. Apart from the control of GTP–GDP cycling, Rho GTPase activity is spatially and temporally regulated by post-translation modifications (PTMs) and their assembly onto specific protein complexes, which determine their controlled activity at distinct cellular compartments. Although Rho GTPases were traditionally conceived as targeted from the cytosol to the plasma membrane to exert their activity, recent research demonstrates that active pools of different Rho GTPases also localize to endomembranes and the nucleus. In this review, we discuss how PTM-driven modulation of Rho GTPases provides a versatile mechanism for their compartmentalization and functional regulation. Understanding how the subcellular sorting of active small GTPase pools occurs and what its functional significance is could reveal novel therapeutic opportunities.

Vanadium compounds therapeutic effects in melanoma

Abstract Background Polyoxometalates are a diverse family of metal-oxo anions of early transitional metal ions in high oxidation states, including vanadium. Such compounds are gaining increasing interest in biomedicine due to their anti-cancer activity. Regarding melanoma, available therapies’ effectiveness is still currently limited, commonly leading to relapse. For this reason, it is vital to identify novel anti-cancer agents. Methods To better understand the mechanism of action involved in the anti-cancer vanadium-based compounds in melanoma, we conducted a systematic review. Search was performed in Clinical Trials, Cochrane Library, Pubmed, Scielo, and Web of Science (20/4-8/5/2020). Review articles were excluded. Inclusion criteria considered articles between 2000 and 2020, written in English, in which vanadium compounds were evaluated alone (not combined with other drugs), allowing to recognise the effects exclusively derived from vanadium. Results Based on the inclusion/exclusion criteria, a total of 5 articles, published between 2013 and 2020, were analyzed. All tested compounds, including Oxidovanadium(IV) complexes [VIVO(mpp)2] and [VIVO(ppp)2] (VS3, VS4), reduced cellular viability. Moreover, Vanadium pentoxide (V2O5) and Xyloglucan from Copaifera Langsdorffii complexed with Oxovanadium(IV/V) (XGC:VO), in murine B16F10 cells, and Inorganic anion vanadate (VN), [VIVO (dhp)2] (VS2), and N,N’-ethylenebis (pyridoxylideneiminato) vanadium(IV) complex [Pyr2enV(IV)], in A375 cells, induced apoptosis. VN, VS2 and Pyr2enV(IV) increased reactive oxygen species (ROS) levels in A375 cells. In vivo experiments demonstrated that V2O5 prolonged the life of mice implanted with B16F10 cells, with no systemic toxicity. Conclusions Several different vanadium-based compounds have anti-cancer potential in melanoma, mainly increasing apoptosis and ROS production. Specific metal-based complexes are potential melanoma treatments, which might have been previously neglected.

Invasion and egress cascade in intracellular protozoa: Part 2 (T. gondii)

As an apicomplexan member, T. gondii has a complex life cycle that involves multiplication within vertebrate and invertebrate hosts by specialized cell-invasive and egressed life cycle stages, called zoites. They are unique eukaryotic cells with characteristic four main sub-cellular structures. They include a specific inner membrane complex beneath the plasma membrane, an apical “conoid” to sustain parasite micro-tubular cytoskeleton, a plastid responsible for lipids synthesis, and specific secretory organelles; micronemes (MICs), rhoptries (ROs) and dense granules (DGs). The last is involved in maturation of the parasitophorous vacuole (PV), where the parasite multiplies; the first essential step after invasion and before egress. Similar to Plasmodium sp., successful invasion and egress cascade accounts mainly on efficient rapid invasion without alteration of host cell cytoskeleton, and multiplication within host cells inside its PV. However, Plasmodium sp. export proteins into host cell cytoplasm and plasma membrane utilizing PV as a trafficking vehicle. Instead, PV of T. gondii zoites utilized abundantly expressed DGs and ROs proteins to build up the intra-vacuolar membranous network (IVMN) for trafficking. The present editorial aims to clarify roles of proteins released from MICs, ROs and DGs in invasion and egress cascade of T. gondii.