Inorganic Nanoparticles: Tools to Emphasize the Janus Face of Amphotericin B.

Amphotericin B is the oldest antifungal molecule which is still currently widely used in clinical practice, in particular for the treatment of invasive diseases, even though it is not devoid of side effects (particularly nephrotoxicity). Recently, its redox properties (i.e., both prooxidant and antioxidant) have been highlighted in the literature as mechanisms involved in both its activity and its toxicity. Interestingly, similar properties can be described for inorganic nanoparticles. In the first part of the present review, the redox properties of Amphotericin B and inorganic nanoparticles are discussed. Then, in the second part, inorganic nanoparticles as carriers of the drug are described. A special emphasis is given to their combined redox properties acting either as a prooxidant or as an antioxidant and their connection to the activity against pathogens (i.e., fungi, parasites, and yeasts) and to their toxicity. In a majority of the published studies, inorganic nanoparticles carrying Amphotericin B are described as having a synergistic activity directly related to the rupture of the redox homeostasis of the pathogen. Due to the unique properties of inorganic nanoparticles (e.g., magnetism, intrinsic anti-infectious properties, stimuli-triggered responses, etc.), these nanomaterials may represent a new generation of medicine that can synergistically enhance the antimicrobial properties of Amphotericin B.

Photothermal/Photoacoustic Therapy Combined with Metal-Based Nanomaterials for the Treatment of Microbial Infections.

The increased spread and persistence of bacterial drug-resistant phenotypes remains a public health concern and has contributed significantly to the challenge of combating antibiotic resistance. Nanotechnology is considered an encouraging strategy in the fight against antibiotic-resistant bacterial infections; this new strategy should improve therapeutic efficacy and minimize side effects. Evidence has shown that various nanomaterials with antibacterial performance, such as metal-based nanoparticles (i.e., silver, gold, copper, and zinc oxide) have intrinsic antibacterial properties. These antibacterial agents, such as those made of metal oxides, carbon nanomaterials, and polymers, have been used not only to improve antibacterial efficacy but also to reduce bacterial drug resistance due to their interaction with bacteria and their photophysical properties. These nanostructures have been used as effective agents for photothermal therapy (PTT) and photodynamic therapy (PDT) to kill bacteria locally by heating or the controlled production of reactive oxygen species. Additionally, PTT or PDT therapies have also been combined with photoacoustic (PA) imaging to simultaneously improve treatment efficacy, safety, and accuracy. In this present review, we present, on the one hand, a summary of research highlighting the use of PTT-sensitive metallic nanomaterials for the treatment of bacterial and fungal infections, and, on the other hand, an overview of studies showing the PA-mediated theranostic functionality of metal-based nanomaterials.

Natural Products for the Prevention and Treatment of Common Cold and Viral Respiratory Infections.

The common cold is generally considered a usually harmless infectious disease of the upper respiratory pathway, with mostly mild symptoms. However, it should not be overlooked, as a severe cold can lead to serious complications, resulting in hospitalization or death in vulnerable patients. The treatment of the common cold remains purely symptomatic. Analgesics as well as oral antihistamines or decongestants may be advised to relieve fever, and local treatments can clear the airways and relieve nasal congestion, rhinorrhea, or sneezing. Certain medicinal plant specialties can be used as therapy or as complementary self-treatment. Recent scientific advances discussed in more detail in this review have demonstrated the plant's efficiency in the treatment of the common cold. This review presents an overview of plants used worldwide in the treatment of cold diseases.

Squalamine and Its Aminosterol Derivatives: Overview of Biological Effects and Mechanisms of Action of Compounds with Multiple Therapeutic Applications.

Squalamine is a natural aminosterol that has been discovered in the tissues of the dogfish shark (Squalus acanthias). Studies have previously demonstrated that this promoter compound and its derivatives exhibit potent bactericidal activity against Gram-negative, Gram-positive bacteria, and multidrug-resistant bacteria. The antibacterial activity of squalamine was found to correlate with that of other antibiotics, such as colistin and polymyxins. Still, in the field of microbiology, evidence has shown that squalamine and its derivatives have antifungal activity, antiprotozoa effect against a limited list of protozoa, and could exhibit antiviral activity against both RNA- and DNA-enveloped viruses. Furthermore, squalamine and its derivatives have been identified as being antiangiogenic compounds in the case of several types of cancers and induce a potential positive effect in the case of other diseases such as experimental retinopathy and Parkinson's disease. Given the diverse effects of the squalamine and its derivatives, in this review we provide the different advances in our understanding of the various effects of these promising molecules and try to draw up a non-exhaustive list of the different mechanisms of actions of squalamine and its derivatives on the human organism and on different pathogens.

Current Knowledge on the Oxidative-Stress-Mediated Antimicrobial Properties of Metal-Based Nanoparticles.

The emergence of multidrug-resistant (MDR) bacteria in recent years has been alarming and represents a major public health problem. The development of effective antimicrobial agents remains a key challenge. Nanotechnologies have provided opportunities for the use of nanomaterials as components in the development of antibacterial agents. Indeed, metal-based nanoparticles (NPs) show an effective role in targeting and killing bacteria via different mechanisms, such as attraction to the bacterial surface, destabilization of the bacterial cell wall and membrane, and the induction of a toxic mechanism mediated by a burst of oxidative stress (e.g., the production of reactive oxygen species (ROS)). Considering the lack of new antimicrobial drugs with novel mechanisms of action, the induction of oxidative stress represents a valuable and powerful antimicrobial strategy to fight MDR bacteria. Consequently, it is of particular interest to determine and precisely characterize whether NPs are able to induce oxidative stress in such bacteria. This highlights the particular interest that NPs represent for the development of future antibacterial drugs. Therefore, this review aims to provide an update on the latest advances in research focusing on the study and characterization of the induction of oxidative-stress-mediated antimicrobial mechanisms by metal-based NPs.

Plant-Derived Antimicrobial Peptides as Potential Antiviral Agents in Systemic Viral Infections.

Numerous studies have led to a better understanding of the mechanisms of action of viruses in systemic infections for the development of prevention strategies and very promising antiviral therapies. Viruses still remain one of the main causes of human diseases, mainly because the development of new vaccines is usually challenging and drug resistance has become an increasing concern in recent decades. Therefore, the development of potential antiviral agents remains crucial and is an unmet clinical need. One abundant source of potential therapeutic molecules are plants: they biosynthesize a myriad of compounds, including peptides which can have antimicrobial activity. Our objective is to summarize the literature on peptides with antiviral properties derived from plants and to identify key features of these peptides and their application in systemic viral infections. This literature review highlights studies including clinical trials which demonstrated that plant cyclotides have the ability to inhibit the growth of viruses causing human diseases, defensin-like peptides possess anti-HIV-1 activity, and lipid transfer proteins and some lectins exhibit a varied antimicrobial profile. To conclude, plant peptides remain interesting to explore in the context of emerging and re-emerging infectious diseases.

Correction to: Relationship between Toxoplasma gondii seropositivity and schizophrenia in the Lebanese population: potential implication of genetic polymorphism of MMP-9.

An amendment to this paper has been published and can be accessed via the original article.

Relationship between Toxoplasma gondii seropositivity and schizophrenia in the Lebanese population: potential implication of genetic polymorphism of MMP-9.

BACKGROUND: Toxoplasma multiplication and its persistence into the brain cause a local neuroinflammatory reaction, resulting synthesis of neurotransmitters involved in neurological disorders, especially schizophrenia. The Matrix metallopeptidase 9 (MMP-9) protein can play a major role in this neuroinflammation. It can promote extravasation and migration of infected immune cells into the brain. The objectives of this study are to determine the possible association between schizophrenia and toxoplasmosis and highlight the existence of gene polymorphism encoding MMP-9 protein's in patients presented both schizophrenia and toxoplasmosis. METHODS: A case-control study was conducted on 150 patients with schizophrenia (case group), and 150 healthy persons (control group). Groups were matched with age, gender, and place of residence. The survey was conducted using a questionnaire and a serological profile assay for specific IgG and IgM antibodies against T. gondii. Reverse transcription-polymerase chain reaction (RT-PCR) of gene polymorphism encoding MMP-9 was performed on 83 cases selected randomly. RESULTS: Data show a significant association between toxoplasmosis (IgM+/IgG+ serological profile) and schizophrenia. Significant effects of raw meat consumption and contact with cats have been associated with the occurrence of schizophrenia. RT-PCR shows the presence of muted allele of MMP-9 gene in selected cases whose present T. gondii serological profile IgM+/IgG+ and IgM-/IgG+ respectively. CONCLUSION: Toxoplasmosis may be one of the etiological causes of schizophrenia, and MMP-9 gene polymorphism could be involved in the occurrence mechanism of this pathology following Toxoplasma infection.

Toxoplasma gondii Modulates the Host Cell Responses: An Overview of Apoptosis Pathways.

Infection with Toxoplasma gondii has a major implication in public health. Toxoplasma gondii is an obligate intracellular protozoan parasite that can infect all nucleated cells belonging to a wide range of host species. One of the particularities of this parasite is its invasion and persistence in host cells of immunocompetent people. This infection is usually asymptomatic. In immunocompromised patients, the infection is severe and symptomatic. The mechanisms by which T. gondii persists are poorly studied in humans. In mouse models, many aspects of the interaction between the parasite and the host cells are being studied. Apoptosis is one of these mechanisms that could be modulated by Toxoplasma to persist in host cells. Indeed, Toxoplasma has often been implicated in the regulation of apoptosis and viability mechanisms in both human and murine infection models. Several of these studies centered on the regulation of apoptosis pathways have revealed interference of this parasite with host cell immunity, cell signalling, and invasion mechanisms. This review provides an overview of recent studies concerning the effect of Toxoplasma on different apoptotic pathways in infected host cells.

Clonal deleted latent membrane protein 1 variants of Epstein-Barr virus are predominant in European extranodal NK/T lymphomas and disappear during successful treatment.

Extranodal natural killer/T-cell lymphomas (NK/TL), rare in Europe, are Epstein-Barr virus (EBV) associated lymphomas with poor outcomes. Here, we determined the virus type and analyzed the EBV latent membrane protein-1 (LMP1) gene sequence in NK/TL from French patients. Six clones of viral LMP1 were sequenced by Sanger technology in blood from 13 patients before treatment with an l-asparaginase based regimen and, for 8 of them, throughout the treatment. Blood LMP1 sequences from 21 patients without any known malignancy were tested as controls. EBV Type A was identified for 11/13 patients and for all controls. Before treatment, a clonal LMP1 gene containing a 30 bp deletion (del30) was found in 46.1% of NK/TL and only in 4.8% of controls. Treatment was less effective in these patients who died more rapidly than the others. Patients with a deleted strain evolving toward a wild-type strain during treatment reached complete remission. The LMP1 gene was sequenced by highly sensitive next-generation sequencing technology in five NK/TL nasopharyngeal biopsies, two of them originating from the previous patients. Del30 was present in 100% of the biopsies; two viruses at least coexisted in three biopsies. These results suggest that del30 may be associated with poor prognosis NK/TL and that strain evolution could be used as a potential marker to monitor treatment.

Interferon gamma effect on immune mediator production in human nerve cells infected by two strains of Toxoplasma gondii.

Interferon gamma (IFN-γ) is the major immune mediator that prevents toxoplasmic encephalitis in murine models. The lack of IFN-γ secretion causes reactivation of latent T. gondii infection that may confer a risk for severe toxoplasmic encephalitis. We analyse the effect of IFN-γ on immune mediator production and parasite multiplication in human nerve cells infected by tachyzoites of two T. gondii strains (RH and PRU). IFN-γ decreased the synthesis of MCP-1, G-CSF, GM-CSF and Serpin E1 in all cell types. It decreased IL-6, migration inhibitory factor (MIF) and GROα synthesis only in endothelial cells, while it increased sICAM and Serpin E1 synthesis only in neurons. The PRU strain burden increased in all nerve cells and in contrast, RH strain replication was controlled in IFN-γ-stimulated microglial and endothelial cells but not in IFN-γ-stimulated neurons. The proliferation of the PRU strain in all stimulated cells could be a specific effect of this strain on the host cell.

In vitro infection of human nervous cells by two strains of Toxoplasma gondii: a kinetic analysis of immune mediators and parasite multiplication.

The severity of toxoplasmic infection depends mainly on the immune status of the host, but also on the Toxoplasma gondii strains, which differ by their virulence profile. The relationship between the human host and T. gondii has not yet been elucidated because few studies have been conducted on human models. The immune mechanisms involved in the persistence of T. gondii in the brains of immunocompetent subjects and during the reactivation of latent infections are still unclear. In this study, we analyzed the kinetics of immune mediators in human nervous cells in vitro, infected with two strains of T. gondii. Human neuroblast cell line (SH SY5Y), microglial (CMH5) and endothelial cells (Hbmec) were infected separately by RH (type I) or PRU (type II) strains for 8 h, 14 h, 24 h and 48 h (ratio 1 cell: 2 tachyzoites). Pro-inflammatory protein expression was different between the two strains and among different human nervous cells. The cytokines IL-6, IL-8 and the chemokines MCP-1 and GROα, and SERPIN E1 were significantly increased in CMH5 and SH SY5Y at 24 h pi. At this point of infection, the parasite burden declined in microglial cells and neurons, but remained high in endothelial cells. This differential effect on the early parasite multiplication may be correlated with a higher production of immune mediators by neurons and microglial cells compared to endothelial cells. Regarding strain differences, PRU strain, but not RH strain, stimulates all cells to produce pro-inflammatory growth factors, G-CSF and GM-CSF. These proteins could increase the inflammatory effect of this type II strain. These results suggest that the different protein expression profiles depend on the parasitic strain and on the human nervous cell type, and that this could be at the origin of diverse brain lesions caused by T. gondii.