The effects of Phycocyanobilin on experimental arthritis involve the reduction in nociception and synovial neutrophil infiltration, inhibition of cytokine production, and modulation of the neuronal proteome.

Introduction: The antinociceptive and pharmacological activities of C-Phycocyanin (C-PC) and Phycocyanobilin (PCB) in the context of inflammatory arthritis remain unexplored so far. In the present study, we aimed to assess the protective actions of these compounds in an experimental mice model that replicates key aspects of human rheumatoid arthritis.

Methods: Antigen-induced arthritis (AIA) was established by intradermal injection of methylated bovine serum albumin in C57BL/6 mice, and one hour before the antigen challenge, either C-PC (2, 4, or 8 mg/kg) or PCB (0.

Evidence of SARS-CoV-2 infection in postmortem lung, kidney, and liver samples, revealing cellular targets involved in COVID-19 pathogenesis.

There is an urgent need to understand severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-host interactions involved in virus spread and pathogenesis, which might contribute to the identification of new therapeutic targets. In this study, we investigated the presence of SARS-CoV-2 in postmortem lung, kidney, and liver samples of patients who died with coronavirus disease (COVID-19) and its relationship with host factors involved in virus spread and pathogenesis, using microscopy-based methods. The cases analyzed showed advanced stages of diffuse acute alveolar damage and fibrosis.

Anti-inflammatory mechanisms and pharmacological actions of phycocyanobilin in a mouse model of experimental autoimmune encephalomyelitis: A therapeutic promise for multiple sclerosis.

Cytokines, demyelination and neuroaxonal degeneration in the central nervous system are pivotal elements implicated in the pathogenesis of multiple sclerosis (MS) and its nonclinical model of experimental autoimmune encephalomyelitis (EAE). Phycocyanobilin (PCB), a chromophore of the biliprotein C-Phycocyanin (C-PC) from , has antioxidant, immunoregulatory and anti-inflammatory effects in this disease, and it could complement the effect of other Disease Modifying Treatments (DMT), such as Interferon-β (IFN-β). Here, our main goal was to evaluate the potential PCB benefits and its mechanisms of action to counteract the chronic EAE in mice.

Positive effects of Phycocyanobilin on gene expression in glutamate-induced excitotoxicity in SH-SY5Y cells and animal models of multiple sclerosis and cerebral ischemia.

Background: Oxidative stress has a predominant role in the pathogenesis of neurodegenerative diseases and therefore the modulation of genes and the identification of biological pathways associated with antioxidant therapies, have an impact on its treatment.

Objective: The objective of this study was the comparison of 2 methods for the analysis of real-time PCR (qPCR) data, through the use of the evaluation of genes that mediate the effect of Phycocyanobilin (PCB) and its validation in animal models.

Methods: We evaluated the effect of PCB:" in vitro" on gene modulation through qPCR analyzed by parametric ANOVA and multivariate principal component analysis (PCA) in a model of glutamate-induced excitotoxicity in the SH-SY5Y cell line and" in vivo"; in animal models of multiple sclerosis (MS) and cerebral ischemia (CI).

Novel Insights into the Molecular Mechanisms Involved in the Neuroprotective Effects of C-Phycocyanin against Brain Ischemia in Rats.

Background: Ischemic stroke produces a large health impact worldwide, with scarce therapeutic options.

Objective: This study aimed to reveal the role of NADPH oxidase and neuroinflammatory genes in the cerebral anti-ischemic effects of C-Phycocyanin (C-PC), the chief biliprotein of Spirulina platensis.

Methods: Rats with either focal cerebral ischemia/reperfusion (I/R) or acute brain hypoperfusion, received C-PC at different doses, or a vehicle, for up to 6 h post-stroke.

The microglial NLRP3 inflammasome is involved in human SARS-CoV-2 cerebral pathogenicity: A report of three post-mortem cases.

We herein report, by using confocal immunofluorescence, the colocalization of the SARS-CoV-2 nucleocapsid within neurons, astrocytes, oligodendrocytes and microglia in three deceased COVID-19 cases, of between 78 and 85 years of age at death. The viral nucleocapsid was detected together with its ACE2 cell entry receptor, as well as the NLRP3 inflammasome in cerebral cortical tissues. It is noteworthy that NLRP3 was colocalized with CD68 + macrophages in the brain and lung of the deceased, suggesting the critical role of this type of inflammasome in SARS-CoV-2 lesions of the nervous system/lungs and supporting its potential role as a therapeutic target.

C-Phycocyanin-derived Phycocyanobilin as a Potential Nutraceutical Approach for Major Neurodegenerative Disorders and COVID-19- induced Damage to the Nervous System.

The edible cyanobacterium Spirulina platensis and its chief biliprotein C-Phycocyanin have shown protective activity in animal models of diverse human health diseases, often reflecting antioxidant and anti-inflammatory effects. The beneficial effects of C-Phycocyanin seem likely to be primarily attributable to its covalently attached chromophore Phycocyanobilin (PCB). Within cells, biliverdin is generated from free heme and it is subsequently reduced to bilirubin.

Phycocyanobilin is the molecule responsible for the nephroprotective action of phycocyanin in acute kidney injury caused by mercury.

C-Phycocyanin (CPC) exerts therapeutic, antioxidant, anti-inflammatory and immunomodulatory actions. It prevents oxidative stress and acute kidney damage caused by HgCl. However, the exact mechanism of the pharmacological action of C-phycocyanin is as yet unclear.

Phycocyanobilin reduces brain injury after endothelin-1- induced focal cerebral ischaemia.

Pharmacological therapies for interrupting biochemical events of the ischaemic cascade and protecting against stroke in humans are as yet unavailable. Up to now, the neuroprotective activity in cerebral ischaemia of phycocyanobilin (PCB), a tetrapyrrolic natural antioxidant, has not been fully examined. Here, we evaluated if PCB protects PC12 neuronal cells against oxygen and glucose deprivation plus reperfusion, and its protective effects in a rat model of endothelin-1-induced focal brain ischaemia.

C-Phycocyanin and Phycocyanobilin as Remyelination Therapies for Enhancing Recovery in Multiple Sclerosis and Ischemic Stroke: A Preclinical Perspective.

Myelin loss has a crucial impact on behavior disabilities associated to Multiple Sclerosis (MS) and Ischemic Stroke (IS). Although several MS therapies are approved, none of them promote remyelination in patients, limiting their ability for chronic recovery. With no available therapeutic options, enhanced demyelination in stroke survivors is correlated with a poorer behavioral recovery.

Report on the Symposium "Molecular Mechanisms Involved in Neurodegeneration".

The prevalence of neurodegenerative diseases is currently a major concern in public health because of the lack of neuroprotective and neuroregenerative drugs. The symposium on Molecular Mechanisms Involved in Neurodegeneration held in Varadero, Cuba, updated the participants on the basic mechanisms of neurodegeneration, on the different approaches for drug discovery, and on early research results on therapeutic approaches for the treatment of neurodegenerative diseases. Alzheimer's disease and in silico research were covered by many of the presentations in the symposium, under the umbrella of the "State of the Art of Non-clinical Models for Neurodegenerative Diseases" International Congress, held from 20 to 24 June 2017.

Beneficial effects of oral administration of C-Phycocyanin and Phycocyanobilin in rodent models of experimental autoimmune encephalomyelitis.

Unlabelled: The only three oral treatments currently available for multiple sclerosis (MS) target the relapsing forms of the disease and concerns regarding efficacy, safety and tolerability limit their use. Identifying novel oral disease-modifying therapies for MS, targeting both its inflammatory and neurodegenerative components is still a major goal.

Aim: The scope of this study was to provide evidence that the oral administration of C-Phycocyanin (C-PC), the main biliprotein of the Spirulina platensis cyanobacteria and its tetrapyrrolic prosthetic group, Phycocyanobilin (PCB), exert ameliorating actions on rodent models of experimental autoimmune encephalomyelitis (EAE).

Comparative Neuroregenerative Effects of C-Phycocyanin and IFN-Beta in a Model of Multiple Sclerosis in Mice.

Multiple Sclerosis (MS) therapies approved so far are unable to effectively reverse the chronic phase of the disease or improve the remyelination process. Here our aim is to evaluate the effects of C-Phycocyanin (C-Pc), a biliprotein from Spirulina platensis with anti-oxidant, anti-inflammatory and cytoprotective properties, in a chronic model of experimental autoimmune encephalomyelitis (EAE) in mice. C-Pc (2, 4 or 8 mg/kg i.

Perspectives in immunopharmacology: the future of immunosuppression.

Modulation of immune responses for therapeutic purposes is a particularly relevant area, given the central role of anomalous immunity in a wide variety of diseases, from the most typically immune-related syndromes (autoimmune diseases, allergy and asthma, immunodeficiencies) to those in which altered immunity and inflammation define the pathological outcomes (chronic infections, tumors, chronic inflammatory and degenerative diseases, metabolic disorders, etc.). This brief review will summarize some of the most promising perspectives of immunopharmacology, in particular in the area of immunosuppression, by considering the following aspects:

Phycocyanobilin promotes PC12 cell survival and modulates immune and inflammatory genes and oxidative stress markers in acute cerebral hypoperfusion in rats.

Since the inflammatory response and oxidative stress are involved in the stroke cascade, we evaluated here the effects of Phycocyanobilin (PCB, the C-Phycocyanin linked tetrapyrrole) on PC12 cell survival, the gene expression and the oxidative status of hypoperfused rat brain. After the permanent bilateral common carotid arteries occlusion (BCCAo), the animals were treated with saline or PCB, taking samples 24h post-surgery. Global gene expression was analyzed with GeneChip Rat Gene ST 1.

The role of glial cells in Alzheimer disease: potential therapeutic implications.

Introduction: Alzheimer (AD) disease is a complex neurodegenerative disease characterised by inflammation, neurotoxicity, oxidative stress, and reactive gliosis. Microglia and astrocytes not only act as antigen-presenting cells, but also function as effector cells releasing pro-inflammatory molecules that promote excitotoxicity and neurodegeneration.

Objective: In the present review we discuss the role of glia, specifically microglia and astrocytes, in the pathophysiology of AD and possible therapeutic implications.

C-Phycocyanin protects SH-SY5Y cells from oxidative injury, rat retina from transient ischemia and rat brain mitochondria from Ca2+/phosphate-induced impairment.

Oxidative stress and mitochondrial impairment are essential in the ischemic stroke cascade and eventually lead to tissue injury. C-Phycocyanin (C-PC) has previously been shown to have strong antioxidant and neuroprotective actions. In the present study, we assessed the effects of C-PC on oxidative injury induced by tert-butylhydroperoxide (t-BOOH) in SH-SY5Y neuronal cells, on transient ischemia in rat retinas, and in the calcium/phosphate-induced impairment of isolated rat brain mitochondria (RBM).

C-Phycocyanin is neuroprotective against global cerebral ischemia/reperfusion injury in gerbils.

Although the huge economic and social impact and the predicted incidence increase, neuroprotection for ischemic stroke remains as a therapeutically empty niche. In the present study, we investigated the rationale of the C-Phycocyanin (C-PC) treatment on global cerebral ischemia/reperfusion (I/R) injury in gerbils. We demonstrated that C-PC given either prophylactically or therapeutically was able to significantly reduce the infarct volume as assessed by triphenyltetrazolium chloride (TTC) staining and the neurological deficit score 24h post-stroke.

C-Phycocyanin ameliorates experimental autoimmune encephalomyelitis and induces regulatory T cells.

For decades Experimental Autoimmune Encephalitis (EAE) has remained as an unsurpassed multiple sclerosis (MS) animal model. C-Phycocyanin (C-Pc) has been reported to exhibit pharmacological properties that may be expected to symptomatically improve EAE and MS. However, in this paper we reveal a basic underlying mechanism that may provide a new approach to the rationale of the overall beneficial effect of this natural antioxidant.

TNF-alpha and IL-10 downregulation and marked oxidative stress in Neuromyelitis Optica.

Background: Neuromyelitis optica is a central nervous system demyelinating and inflammatory syndrome. The objective of this study is to identify cytokines related to the cellular immune response as well as blood brain barrier integrity and oxidative stress.

Methods: We performed a molecular characterization of cellular immune response and oxidative stress in serum from relapsing-NMO (R-NMO) patients and established the correlations between the clinical measurements and molecular parameters using the Bayesian approach.

[Immune response in optic neuromyelitis].

The Optic Neuromyelitis is an inflammatory and autoimmune illness of the central nervous system. Presently work is carried out a revision of the different mechanisms involved in the pathogenesis of the Optic Neuromyelitis, the paper of the eosinophils is analyzed, of the antibodies against own antigens and of the regulatory T cells in the illness. In the Optic Neuromyelitis is very important the humoral response, the illness exists it is characterized by the immunocomplex deposit, activation of the complement, production of antibodies against proteins of the myelin and eosinophils recruitment in the lesions.

[Optic neuromyelitis. Main differences with multiple sclerosis].

The optic neuromyelitis or syndrome of Devic is an inflammatory and autoimmune illness of the central nervous system. It is characterized by attacks of optic neuritis and myelitis, being able to produce blindness, great neurological disability and even the short term death. Until the moment an effective treatment doesn't exist, the therapy is centred in the treatment of the acute attacks, the medical prevention of the complications and the rehabilitation.

Treatment with type I interferons induces a regulatory T cell subset in peripheral blood mononuclear cells from multiple sclerosis patients.

Type I Interferon (IFN-alpha/beta) therapy has altered the natural course of multiple sclerosis. In this paper we evaluate the possible molecular mechanisms involved in the in vitro effects of IFN-alpha/beta on peripheral blood mononuclear cells from patients with clinically definite Relapsing-Remitting Multiple Sclerosis. The total RNA from IFN-alpha, IFN-beta treated cells and untreated cells was extracted and amplified for CD86, CD28, CTLA-4, TNF-alpha, IFN-gamma, CCL2, CCR5, IL-13, MMP-9, TIMP-1, CD25, TGF-beta, IL-10 and the transcriptional factor Foxp3 by Reverse Transcription-Polymerase Chain Reaction and the CD4+CD25high subset was evaluated using flow cytometry.

Construction, purification, and characterization of a chimeric TH1 antagonist.

Background: TH1 immune response antagonism is a desirable approach to mitigate some autoimmune and inflammatory reactions during the course of several diseases where IL-2 and IFN-gamma are two central players. Therefore, the neutralization of both cytokines could provide beneficial effects in patients suffering from autoimmune or inflammatory illnesses.

Results: A chimeric antagonist that can antagonize the action of TH1 immunity mediators, IFN-gamma and IL-2, was designed, engineered, expressed in E.