Isolated Peptide from Spider Venom Modulates Dendritic Cells In Vitro: A Possible Application in Oncoimmunotherapy for Glioblastoma.

Dendritic cells (DCs) vaccine is a potential tool for oncoimmunotherapy. However, it is known that this therapeutic strategy has failed in solid tumors, making the development of immunoadjuvants highly relevant. Recently, we demonstrated that spider venom (PnV) components are cytotoxic to glioblastoma (GB) and activate macrophages for an antitumor profile.

Isolated Components From Spider Venom Targeting Human Glioblastoma Cells and Its Potential Combined Therapy With Rapamycin.

Glioblastomas (GBs) are responsible for a higher mortality rate among gliomas, corresponding to more than 50% of them and representing a challenge in terms of therapy and prognosis. Peptide-based antineoplastic therapy is a vast and promising field, and these molecules are one of the main classes present in spider venoms. Recently, our research group demonstrated the cytotoxic effects of spider venom (PnV) in GBs.

The SNX-482 peptide from Hysterocrates gigas spider acts as an immunomodulatory molecule activating macrophages.

Peptides are molecules that have emerged as crucial candidates for the development of anticancer drugs. Spider venoms are a rich source of peptides (venom peptides - VPs) with biological effects. VPs have been tested as adjuvants in the activation of cells of the immune system with the aim of improving immunotherapies for the treatment of neoplasms.

Sildenafil Alleviates Murine Experimental Autoimmune Encephalomyelitis by Triggering Autophagy in the Spinal Cord.

Multiple Sclerosis (MS) is a neuroinflammatory and chronic Central Nervous System (CNS) disease that affects millions of people worldwide. The search for more promising drugs for the treatment of MS has led to studies on Sildenafil, a phosphodiesterase type 5 Inhibitor (PDE5I) that has been shown to possess neuroprotective effects in the Experimental Autoimmune Encephalomyelitis (EAE), an animal model of MS. We have previously shown that Sildenafil improves the clinical score of EAE mice modulation of apoptotic pathways, but other signaling pathways were not previously covered.

Components from spider venom activate macrophages against glioblastoma cells: new potential adjuvants for anticancer immunotherapy.

Immunomodulation has been considered an important approach in the treatment of malignant tumours. However, the modulation of innate immune cells remains an underexplored tool. Studies from our group demonstrated that the Phoneutria nigriventer spider venom (PnV) administration increased the infiltration of macrophage in glioblastoma, in addition to decreasing the tumour size in a preclinical model.

Lung CD103 Dendritic cells of mice infected with Paracoccidioides brasiliensis contribute to Treg differentiation.

The DC subsets that express αE integrin (CD103) have been described to exert antagonistic functions, driving T cells towards either an inflammatory (Th1/Th17) or immunosuppressive phenotype (regulatory T cells - Treg). These functions depend on the tissue they reside and microenvironment factors or stimuli that this Antigen-presenting cell (APC) subpopulation receive. In this regard, immunoregulatory phenotype has been described in small subsets of CD103 DCs from lung and intestinal mucosa.

Spider venom components decrease glioblastoma cell migration and invasion through RhoA-ROCK and Na/K-ATPase β2: potential molecular entities to treat invasive brain cancer.

Background: Glioblastoma (GB) cells have the ability to migrate and infiltrate the normal parenchyma, leading to the formation of recurrent tumors often adjacent to the surgical extraction site. We recently showed that Phoneutria nigriventer spider venom (PnV) has anticancer effects mainly on the migration of human GB cell lines (NG97 and U-251). The present work aimed to investigate the effects of isolated components from the venom on migration, invasiveness, morphology and adhesion of GB cells, also evaluating RhoA-ROCK signaling and Na/K-ATPase β2 (AMOG) involvement.

Effect of sildenafil on neuroinflammation and synaptic plasticity pathways in experimental autoimmune encephalomyelitis.

Multiple sclerosis (MS) is a chronic immuno-inflammatory disease of the central nervous system characterized by demyelination and axonal damage. Cognitive changes are common in individuals with MS since inflammatory molecules secreted by microglia interfere with the physiological mechanisms of synaptic plasticity. According to previous data, inhibition of PDE5 promotes the accumulation of cGMP, which inhibits neuroinflammation and seems to improve synaptic plasticity and memory.

Spider venom administration impairs glioblastoma growth and modulates immune response in a non-clinical model.

Molecules from animal venoms are promising candidates for the development of new drugs. Previous in vitro studies have shown that the venom of the spider Phoneutria nigriventer (PnV) is a potential source of antineoplastic components with activity in glioblastoma (GB) cell lines. In the present work, the effects of PnV on tumor development were established in vivo using a xenogeneic model.

Semaphorin-3A-Related Reduction of Thymocyte Migration in Chemically Induced Diabetic Mice.

Background: Previous work revealed the existence of a severe thymic atrophy with massive loss of immature CD4+CD8+ thymocytes in animals developing insulin-dependent diabetes, chemically induced by alloxan. Furthermore, the intrathymic expression of chemokines, such as CXCL12, is changed in these animals, suggesting that cell migration-related patterns may be altered. One molecular interaction involved in normal thymocyte migration is that mediated by soluble semaphorin-3A and its cognate receptor neuropilin-1.

Venom of the Phoneutria nigriventer spider alters the cell cycle, viability, and migration of cancer cells.

The mechanisms of cancer involve changes in multiple biological pathways. Multitarget molecules, which are components of animal venoms, are therefore a potential strategy for treating tumors. The objective of this study was to screen the effects of Phoneutria nigriventer spider venom (PnV) on tumor cell lines.

The impact of metabolic reprogramming on dendritic cell function.

Dendritic cells (DCs) are antigen-presenting cells with the ability to activate naïve T cells and direct the adaptive cellular immune response toward a specific profile. This is important, as different pathogens demand specific "profiles" of immune responses for their elimination. Such a goal is achieved depending on the maturation/activation status of DCs by the time of antigen presentation to T cells.

Sildenafil ameliorates EAE by decreasing apoptosis in the spinal cord of C57BL/6 mice.

Apoptosis is one form of cell death that is intimately related to health and pathological conditions. In most neuroinflammatory and/or neurodegenerative diseases, apoptosis is associated with disease development and pathology and inhibition of this process leads to considerable amelioration. It is becoming evident that apoptosis also participates in the pathogenesis of Multiple Sclerosis (MS) and its animal model, Experimental Autoimmune Encephalomyelitis (EAE).

Chloroquine-treated dendritic cells require STAT1 signaling for their tolerogenic activity.

MS and EAE are T cell-driven autoimmune diseases of the CNS where IL-17-producing Th17 cells promote damage and are pathogenic. Conversely, tolerogenic DCs induce Treg cells and suppress Th17 cells. Chloroquine (CQ) suppresses EAE through the modulation of DCs by unknown mechanisms.

Inhibition of hypoxia-associated response and kynurenine production in response to hyperbaric oxygen as mechanisms involved in protection against experimental cerebral malaria.

Cerebral malaria (CM) is a multifactorial syndrome involving an exacerbated proinflammatory status, endothelial cell activation, coagulopathy, hypoxia, and accumulation of leukocytes and parasites in the brain microvasculature. Despite significant improvements in malaria control, 15% of mortality is still observed in CM cases, and 25% of survivors develop neurologic sequelae for life-even after appropriate antimalarial therapy. A treatment that ameliorates CM clinical signs, resulting in complete healing, is urgently needed.

Photodynamic inactivation of Paracoccidioides brasiliensis helps the outcome of oral paracoccidiodomycosis.

The antifungal drug therapy often employed to treat paracoccidiodomycosis (PCM), an important neglected fungal systemic infection, leads to offensive adverse effects, besides being very long-lasting. In addition, PCM compromises the oral health of patients by leading to oral lesions that are very painful and disabling. In that way, photodynamic therapy (PDT) arises as a new promising adjuvant treatment for inactivating Paracoccidioides brasiliensis (Pb), the responsible fungus for PCM, and also for helping the patients to deal with such debilitating oral lesions.

Correction: Severe Changes in Thymic Microenvironment in a Chronic Experimental Model of Paracoccidioidomycosis.

[This corrects the article DOI: 10.1371/journal.pone.

Astroglioma conditioned medium increases synaptic elimination and correlates with major histocompatibility complex of class I (MHC I) upregulation in PC12Cells.

Astrocytes are multifunctional glial cells that actively participate in synaptic plasticity in health and disease. Little is known about molecular interactions between neurons and glial cells that result in synaptic stability or elimination. In this sense, the main histocompatibility complex of class I (MHC I) has been shown to play a role in the synaptic plasticity process during development and after lesion of the CNS.

Correction: MHC-I and PirB Upregulation in the Central and Peripheral Nervous System Following Sciatic Nerve Injury.

[This corrects the article DOI: 10.1371/journal.pone.

Severe Changes in Thymic Microenvironment in a Chronic Experimental Model of Paracoccidioidomycosis.

T cell maturation takes place within the thymus, a primary lymphoid organ that is commonly targeted during infections. Previous studies showed that acute infection with Paracoccidioides brasiliensis (Pb), the causative agent of paracoccidioidomycosis (PCM), promotes thymic atrophy that is associated with the presence of yeast cells in the organ. However, as human PCM is a chronic infection, it is imperative to investigate the consequences of Pb infection over the thymic structure and function in chronic infection.

MHC-I and PirB Upregulation in the Central and Peripheral Nervous System following Sciatic Nerve Injury.

Major histocompatibility complex class one (MHC-I) antigen-presenting molecules participate in central nervous system (CNS) synaptic plasticity, as does the paired immunoglobulin-like receptor B (PirB), an MHC-I ligand that can inhibit immune-cells and bind to myelin axon growth inhibitors. Based on the dual roles of both molecules in the immune and nervous systems, we evaluated their expression in the central and peripheral nervous system (PNS) following sciatic nerve injury in mice. Increased PirB and MHC-I protein and gene expression is present in the spinal cord one week after nerve transection, PirB being mostly expressed in the neuropile region.

Enhanced Immune Response in Immunodeficient Mice Improves Peripheral Nerve Regeneration Following Axotomy.

Injuries to peripheral nerves cause loss of motor and sensory function, greatly affecting life quality. Successful repair of the lesioned nerve requires efficient cell debris removal, followed by axon regeneration and reinnervation of target organs. Such process is orchestrated by several cellular and molecular events in which glial and immune cells actively participate.

Tolerogenic Vaccination with MOG/VitD Overcomes Aggravating Effect of C. albicans in Experimental Encephalomyelitis.

Aims: Multiple sclerosis (MS) is an immune-mediated demyelinating disorder of the central nervous system (CNS). We described that Candida albicans (Ca) aggravates experimental autoimmune encephalomyelitis (EAE) that is a model to study MS. We also observed that vaccination with a myelin peptide (MOG) in the presence of vitamin D (VitD) protected mice against EAE.

Paracoccidioides brasiliensis infection promotes thymic disarrangement and premature egress of mature lymphocytes expressing prohibitive TCRs.

Background: Paracoccidioidomycosis, a chronic granulomatous fungal disease caused by Paracoccidioides brasiliensis yeast cells affects mainly rural workers, albeit recently cases in immunosuppressed individuals has been reported. Protective immune response against P. brasiliensis is dependent on the activity of helper T cells especially IFN-γ-producing Th1 cells.

Artesunate Ameliorates Experimental Autoimmune Encephalomyelitis by Inhibiting Leukocyte Migration to the Central Nervous System.

Background And Aims: Experimental autoimmune encephalomyelitis (EAE) is T-cell-dependent disease of the central nervous system (CNS) of mice. This model resembles multiple sclerosis (MS) in many aspects. Therapies that focus in the modulation of the immune response and cellular infiltration in the CNS present best effects in the clinics.