Design of Natterins-based peptides improves antimicrobial and antiviral activities.

The biochemical analysis of animal venoms has been intensifying over the years, enabling the prediction of new molecules derived from toxins, harnessing the therapeutic potential of these molecules. From the venom of the fish , using methods for predicting antimicrobial and cell-penetrating peptides, two peptides from Natterins with promising characteristics were synthesized and subjected to and analysis. The peptides were subjected to stability tests and antimicrobial assays, cytotoxicity in murine fibroblast cells, antiviral assays against the Chikungunya virus, and the toxicity on was also evaluated.

P and AHR-CYP1A1 Signaling Crosstalk in an Injury-Induced Zebrafish Inflammation Model.

Aryl Hydrocarbon Receptor (AHR) signaling is crucial for regulating the biotransformation of xenobiotics and physiological processes like inflammation and immunity. Meanwhile, Peptide (P), a promising anti-inflammatory candidate from toadfish venom, demonstrates therapeutic effects through immunomodulation. However, its influence on AHR signaling remains unexplored.

Pesticide-Induced Inflammation at a Glance.

The increasing number of studies reporting the risks of the exposure to pesticides aligned with the intensified use of such hazardous chemicals has emerged as a pressing contemporary issue, notably due to the potential effects to both the environment and human health. Pesticides, while broadly applied in modern agriculture for pest control and crop protection, have raised concerns due to their unintended effects on non-target organisms. The immune system exerts a key role in the protection against the exposome, which could result in cellular imbalances and tissue damage through the inflammatory response.

Revisiting Retinal Degeneration Hallmarks: Insights from Molecular Markers and Therapy Perspectives.

Visual impairment and blindness are a growing public health problem as they reduce the life quality of millions of people. The management and treatment of these diseases represent scientific and therapeutic challenges because different cellular and molecular actors involved in the pathophysiology are still being identified. Visual system components, particularly retinal cells, are extremely sensitive to genetic or metabolic alterations, and immune responses activated by local insults contribute to biological events, culminating in vision loss and irreversible blindness.

Envenomations caused by fish in Brazil: an evolutionary, morphological, and clinical vision of a neglected problem.

Venomous fish are commonly found in Brazilian waters. The most important marine venomous fish species are stingrays (Dasyatidae, Gimnuridae, Myliobatidae, and Rhinopteridae families), catfish (Ariidae family), scorpionfish and lionfish (both Scorpaenidae family), and toadfish (Batrachoididae family). Meanwhile, Potamotrygonidae stingrays and Pimelodidae catfish are the most important venomous freshwater fish.

Inflammasome Coordinates Senescent Chronic Wound Induced by Venom.

toadfish (niquim) envenomation, common in the hands and feet of bathers and fishermen in the north and northeast regions of Brazil, is characterized by local symptoms such as immediate edema and intense pain. These symptoms progress to necrosis that lasts for an extended period of time, with delayed healing. Wound healing is a complex process characterized by the interdependent role of keratinocytes, fibroblasts, and endothelial and innate cells such as neutrophils and macrophages.

Effective Pre-Clinical Treatment of Fish Envenoming with Polyclonal Antiserum.

Envenomation by venomous fish, although not always fatal, is capable of causing damage to homeostasis by activating the inflammatory process, with the formation of edema, excruciating pain, necrosis that is difficult to heal, as well as hemodynamic and cardiorespiratory changes. Despite the wide variety of pharmacological treatments used to manage acute symptoms, none are effective in controlling envenomation. Knowing the essential role of neutralizing polyclonal antibodies in the treatment of envenoming for other species, such as snakes, this work aimed to produce a polyclonal antiserum in mice and test its ability to neutralize the main toxic effects induced by the venoms of the main venomous Brazilian fish.

The Anti-Inflammatory Peptide P Is a Candidate Molecule for Asthma Treatment.

Asthma is the most common chronic lung disease, with increasing morbidity and mortality worldwide. Accumulation of peribronchial leukocytes is the hallmark of asthma, in particular, eosinophils, which have been reported as the primary cell associated with the induction of airway hyperresponsiveness. Continued exacerbation and accumulation of other leukocytes, such as neutrophils, Th1, and Th17 cells correlate with many of the long-term effects of asthma, such as airway remodeling.

Pesticides and Their Impairing Effects on Epithelial Barrier Integrity, Dysbiosis, Disruption of the AhR Signaling Pathway and Development of Immune-Mediated Inflammatory Diseases.

The environmental and occupational risk we confront from agricultural chemicals increases as their presence in natural habitats rises to hazardous levels, building a major part of the exposome. This is of particular concern in low- and middle-income countries, such as Brazil, known as a leading producer of agricultural commodities and consumer of pesticides. As long as public policies continue to encourage the indiscriminate use of pesticides and governments continue to support this strategy instead of endorsing sustainable agricultural alternatives, the environmental burden that damages epithelial barriers will continue to grow.

Plasma proteome responses in zebrafish following λ-carrageenan-Induced inflammation are mediated by PMN leukocytes and correlate highly with their human counterparts.

Regulation of inflammation is a critical process for maintaining physiological homeostasis. The λ-carrageenan (λ-CGN) is a mucopolysaccharide extracted from the cell wall of red algae () capable of inducing acute intestinal inflammation, which is translated into the production of acute phase reactants secreted into the blood circulation. However, the associated mechanisms in vertebrates are not well understood.

Shedding Light on the Drug-Target Prediction of the Anti-Inflammatory Peptide P with Bioinformatics Tools.

Peptide-protein interactions are involved in various fundamental cellular functions, and their identification is crucial for designing efficacious peptide therapeutics. Drug-target interactions can be inferred by in silico prediction using bioinformatics and computational tools. We patented the P family of synthetic cyclic peptides, which is in the preclinical stage of developmental studies for chronic inflammatory diseases such as multiple sclerosis.

Zebrafish Larvae Behavior Models as a Tool for Drug Screenings and Pre-Clinical Trials: A Review.

To discover new molecules or review the biological activity and toxicity of therapeutic substances, drug development, and research relies on robust biological systems to obtain reliable results. Phenotype-based screenings can transpose the organism's compensatory pathways by adopting multi-target strategies for treating complex diseases, and zebrafish emerged as an important model for biomedical research and drug screenings. Zebrafish's clear correlation between neuro-anatomical and physiological features and behavior is very similar to that verified in mammals, enabling the construction of reliable and relevant experimental models for neurological disorders research.

Short chain fatty acids (SCFAs) improves TNBS-induced colitis in zebrafish.

The short-chain fatty acids (SCFAs) are metabolites originated from the fermentation of dietary fibers and amino acids produced by the bacteria of the intestinal microbiota. The most abundant SCFAs, acetate, propionate, and butyrate, have been proposed as a treatment for inflammatory bowel diseases (IBDs) due to their anti-inflammatory properties. This work aimed to analyze the effects of the treatment of three combined SCFAs in TNBS-induced intestinal inflammation in zebrafish larvae.

Natterin-Induced Neutrophilia Is Dependent on cGAS/STING Activation via Type I IFN Signaling Pathway.

Natterin is a potent pro-inflammatory fish molecule, inducing local and systemic IL-1β/IL-1R1-dependent neutrophilia mediated by non-canonical NLRP6 and NLRC4 inflammasome activation in mice, independent of NLRP3. In this work, we investigated whether Natterin activates mitochondrial damage, resulting in self-DNA leaks into the cytosol, and whether the DNA sensor cGAS and STING pathway participate in triggering the innate immune response. Employing a peritonitis mouse model, we found that the deficiency of the tlr2/tlr4, myd88 and trif results in decreased neutrophil influx to peritoneal cavities of mice, indicative that in addition to MyD88, TRIF contributes to neutrophilia triggered by TLR4 engagement by Natterin.

P Peptide Suppresses Experimental Autoimmune Encephalomyelitis (EAE) in a Preclinical Mouse Model.

P is a family of patented synthetic peptides which is in a preclinical development stage with valuable potential therapeutic indication for multiple sclerosis (MS), an autoimmune demyelinating disease of the central nervous system (CNS). The use of a preclinical animal model, such as experimental autoimmune encephalomyelitis (EAE) has deepened our knowledge of the immunomodulatory functions of P as a drug. We have shown that P possesses a disease suppressive function in EAE, ameliorating disease severity by 40% and suppressing the accumulation of T helper (Th)1- and Th17-producing lymphocytes (by 55% and 60%, respectively) in CNS along with activated microglia/macrophages populations (by 33% and 50%, respectively), and also conferred a protective effect anticipating the remyelination process to day 66 compared to day 83 of untreated cuprizone-mice.

Natterin-like depletion by CRISPR/Cas9 impairs zebrafish (Danio rerio) embryonic development.

Background: The Natterin protein family was first discovered in the venom of the medically significant fish Thalassophryne nattereri, and over the last decade natterin-like genes have been identified in various organisms, notably performing immune-related functions. Previous findings support natterin-like genes as effector defense molecules able to activate multiprotein complexes driving the host innate immune response, notably due to the pore-forming function of the aerolysin superfamily members. Herein, employing a combination of the CRISPR/Cas9 depletion system, phenotype-based screening, and morphometric methods, we evaluated the role of one family member, LOC795232, in the embryonic development of zebrafish since it might be implicated in multiple roles and characterization of the null mutant is central for analysis of gene activity.

Molecular Characterization and Functional Analysis of the Nattectin-like Toxin from the Venomous Fish .

TmC4-47.2 is a toxin with myotoxic activity found in the venom of , a venomous fish commonly found in Latin America whose envenomation produces an injury characterized by delayed neutrophil migration, production of major pro-inflammatory cytokines, and necrosis at the wound site, as well as a specific systemic immune response. However, there are few studies on the protein structure and functions associated with it.

Proteomic analysis capsule synthesis and redox mechanisms in the intracellular survival of group B Streptococcus in fish microglia.

Group B Streptococcus (GBS) causes meningitis in neonates and Nile tilapia (Oreochromis niloticus). The molecular mechanisms regulating the intracellular survival of this pathogen in the host cell are complex and crucial for the progression of infection. Thus, we propose the use of GBS-infected Nile tilapia microglia as an in vitro model system simulating infection caused by homologous bacteria in humans.

The Natterin Proteins Diversity: A Review on Phylogeny, Structure, and Immune Function.

Since the first record of the five founder members of the group of Natterin proteins in the venom of the medically significant fish , new sequences have been identified in other species. In this work, we performed a detailed screening using available genome databases across a wide range of species to identify sequence members of the Natterin group, sequence similarities, conserved domains, and evolutionary relationships. The high-throughput tools have enabled us to dramatically expand the number of members within this group of proteins, which has a remote origin (around 400 million years ago) and is spread across Eukarya organisms, even in plants and primitive Agnathans jawless fish.