scholarly journals Therapeutic Efficacy of Antibacterial Ocellatin Peptides- A Comprehensive Review

2021 ◽  
Vol 12 (5) ◽  
pp. 6804-6814
Keyword(s):  
Therapeutic Efficacy ◽  
Innate Immune ◽  
South American ◽  
Hydrophobic Residues ◽  
Microbial Drug Resistance ◽  
Bacterial Membranes ◽  
Drug Candidates ◽  
Small Molecule Drugs ◽  
Living Organisms ◽  
Dynamic Interplay

Antimicrobial peptides (AMPs), ascribed to their decreased microbial drug resistance, can be employed as potent small-molecule drugs to treat various diseases. AMPs have been conserved in a wide variety of living organisms as a result of the evolution of the innate immune system. Notably, Ocellatin AMPs derived from South American Leptodactylus genus frogs have a higher therapeutic efficacy against infections. Inhibitory activity of Ocellatin AMPs against bacterial membranes is determined by the dynamic interplay of peptide cationic, hydrophobicity, helicity, and amphipathicity. Another advantage of using AMPs as drug candidates is their cell selectivity that is non-hemolytic to human cells. Ocellatin AMPs with optimal hydrophobic residues would therefore be a recommended therapeutic candidate. Henceforth, such AMPs could be used as an alternative strategy in curbing antimicrobial resistance. It is noteworthy that the therapeutic efficacy of Ocellatins is to be appreciated for its broad application as it has been proved to be active against several humans, animal, and plant bacterial pathogens.

scholarly journals Modulation of Innate Immune Toxicity by Silver Nanoparticle Exposure and the Preventive Effects of Pterostilbene

2021 ◽  
Vol 22 (5) ◽  
pp. 2536
Author(s):  
Rong-Jane Chen ◽  
Chiao-Ching Huang ◽  
Rosita Pranata ◽  
Yu-Hsuan Lee ◽  
Yu-Ying Chen ◽  
...  
Keyword(s):  
Silver Nanoparticles ◽  
Good Alternative ◽  
Innate Immune ◽  
Toxic Effects ◽  
Transgenic Zebrafish ◽  
Zebrafish Model ◽  
Cytokines And Chemokines ◽  
Living Organisms ◽  
And Function ◽  
Immune Toxicity

Silver nanoparticles pose a potential risk to ecosystems and living organisms due to their widespread use in various fields and subsequent gradual release into the environment. Only a few studies have investigated the effects of silver nanoparticles (AgNPs) toxicity on immunological functions. Furthermore, these toxic effects have not been fully explored. Recent studies have indicated that zebrafish are considered a good alternative model for testing toxicity and for evaluating immunological toxicity. Therefore, the purpose of this study was to investigate the toxicity effects of AgNPs on innate immunity using a zebrafish model and to investigate whether the natural compound pterostilbene (PTE) could provide protection against AgNPs-induced immunotoxicity. Wild type and neutrophil- and macrophage-transgenic zebrafish lines were used in the experiments. The results indicated that the exposure to AgNPs induced toxic effects including death, malformation and the innate immune toxicity of zebrafish. In addition, AgNPs affect the number and function of neutrophils and macrophages. The expression of immune-related cytokines and chemokines was also affected. Notably, the addition of PTE could activate immune cells and promote their accumulation in injured areas in zebrafish, thereby reducing the damage caused by AgNPs. In conclusion, AgNPs may induce innate immune toxicity and PTE could ameliorate this toxicity.

Fragment-based drug design of nature-inspired compounds

2019 ◽  
Vol 4 (9) ◽  
Author(s):  
Abdulkarim Najjar ◽  
Abdurrahman Olğaç ◽  
Fidele Ntie-Kang ◽  
Wolfgang Sippl
Keyword(s):  
Drug Design ◽  
Small Molecules ◽  
Small Molecule ◽  
Binding Pocket ◽  
Biological Macromolecules ◽  
Drug Candidates ◽  
Fragment Screening ◽  
Small Molecule Drugs ◽  
Lead Generation ◽  
Hit Identification

Abstract Natural product (NP)-derived drugs can be extracts, biological macromolecules, or purified small molecule substances. Small molecule drugs can be originally purified from NPs, can represent semisynthetic molecules, natural fragments containing small molecules, or are fully synthetic molecules that mimic natural compounds. New semisynthetic NP-like drugs are entering the pharmaceutical market almost every year and reveal growing interests in the application of fragment-based approaches for NPs. Thus, several NP databases were constructed to be implemented in the fragment-based drug design (FBDD) workflows. FBDD has been established previously as an approach for hit identification and lead generation. Several biophysical and computational methods are used for fragment screening to identify potential hits. Once the fragments within the binding pocket of the protein are identified, they can be grown, linked, or merged to design more active compounds. This work discusses applications of NPs and NP scaffolds to FBDD. Moreover, it briefly reviews NP databases containing fragments and reports on case studies where the approach has been successfully applied for the design of antimalarial and anticancer drug candidates.

scholarly journals Design of a Novel Synbiotic Formulation to Optimize Gut-derived Phenolic Acid Mediated Gut-brain Axis Signals for the Treatment of Stress-induced Depression and Anxiety (OR23-03-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Susan Westfall ◽  
Giulio Pasinetti
Keyword(s):  
Gut Microbiota ◽  
Therapeutic Efficacy ◽  
Toxicity Testing ◽  
Innate Immune ◽  
Bioactive Metabolites ◽  
Inflammasome Activation ◽  
Funding Sources ◽  
Psychological Impairment

Abstract Objectives Synbiotics, the combination of probiotics and prebiotics, may optimize the production of polyphenolic metabolites, and act as therapeutic agents for inflammation-induced depression. Recent evidence suggests that dysregulated immune activity increases susceptibility to depression and that bioactive polyphenolic metabolites can effectively reduce that inflammation. The problem remains that bioactive metabolite production is dependent on the gut microbiota, leading to significant interpersonal variation in the metabolites’ therapeutic efficacy. The hypothesis of the study is that the synbiotic will standardize production and bioavailability of bioactive metabolites capable of suppressing innate immune biological signatures of depression. Methods To standardize the production of bioactive metabolites, the synbiotic will be designed in an innovative in vitro model of the human gastrointestinal tract using a multivariate regression algorithm to predict which probiotic formulation produces the most effective bioactive metabolites. Following in vivo bioavailability and toxicity testing, the synbiotic's therapeutic efficacy was tested in a chronic unpredictable stress (CUS) mouse model of depression by measuring specific behaviors and changes to the gut microbiota populations. These changes were correlated to biological markers of depression modulated by the synbiotic-derived metabolites including neurobiological markers of depression and variations in innate immune markers, including interleukin-1β (IL-1β). Results In this study, we show that a synbiotic combining a dietary polyphenolic preparation with L. plantarum and B. longum can potentiate the reduction in anxiety and depression in male mice subjected to a 28 day CUS protocol, as compared to polyphenolic treatment alone. Interestingly, we found that the synbiotic may mediate microglia inflammasome activation. This finding was reflected by inhibition of NLRP3-mediated generation of IL-1β in microglia. Conclusions Collectively, these results support the potential role of a synbiotic in the potentiation of attenuation of psychological impairment in a model of depression through mechanisms that involved innate immune NLRP3 inflammation mediation in microglia. Funding Sources This project was funding a P50 CARBON Center grant from the NCCIH/ODS (Pasinetti, PD/PI).

scholarly journals 14-helical β-peptides Elicit Toxicity againstC. albicansby Forming Pores in the Cell Membrane and Subsequently Disrupting Intracellular Organelles

2018 ◽  
Author(s):  
Myung-Ryul Lee ◽  
Namrata Raman ◽  
Patricia Ortiz-Bermudez ◽  
David M. Lynn ◽  
Sean P. Palecek
Keyword(s):  
Cell Death ◽  
Partition Coefficient ◽  
Peptide Binding ◽  
Membrane Disruption ◽  
Bacterial Membranes ◽  
Drug Candidates ◽  
Small Unilamellar Vesicle ◽  
Proteolytic Stability ◽  
Intracellular Organelles ◽  
Insight Into

SummarySynthetic peptidomimetics of antimicrobial peptides are promising as antimicrobial drug candidates because they promote membrane disruption and exhibit greater structural and proteolytic stability. We previously reported selective antifungal 14-helical β-peptides, but the mechanism of antifungal toxicity of β-peptides remains unknown. To provide insight into the mechanism, we studied antifungal β-peptide binding to artificial membranes and livingCandida albicanscells. We investigated the ability of β-peptides to interact with and permeate small unilamellar vesicle models of fungal and bacterial membranes. The partition coefficient supported a pore-mediated mechanism characterized by the existence of a critical β-peptide concentration separating low and high partition coefficient regimes. Live cell intracellular tracking of β-peptides showed that β-peptides translocated into the cytoplasm, and then disrupted the nucleus and vacuole sequentially, leading to cell death. This understanding of the mechanisms of antifungal activity will facilitate design and development of peptidomimetic AMPs, including 14-helical β-peptides, for antifungal applications.Graphical Abstract

scholarly journals The Role of Zinc and Zinc Homeostasis in Macrophage Function

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Hong Gao ◽  
Wei Dai ◽  
Lu Zhao ◽  
Junxia Min ◽  
Fudi Wang
Keyword(s):  
Immune System ◽  
Innate Immune System ◽  
Growth And Development ◽  
Innate Immune ◽  
Zinc Homeostasis ◽  
Zinc Transporters ◽  
Essential Trace Element ◽  
Macrophage Function ◽  
Living Organisms

Zinc has long been recognized as an essential trace element, playing roles in the growth and development of all living organisms. In recent decades, zinc homeostasis was also found to be important for the innate immune system, especially for maintaining the function of macrophages. It is now generally accepted that dysregulated zinc homeostasis in macrophages causes impaired phagocytosis and an abnormal inflammatory response. However, many questions remain with respect to the mechanisms that underlie these processes, particularly at the cellular and molecular levels. Here, we review our current understanding of the roles that zinc and zinc transporters play in regulating macrophage function.

scholarly journals  Innate and adaptive immunity in teleost fish: a review

2011 ◽  
Vol 56 (No. 10) ◽  
pp. 486-503 ◽  
Author(s):  
C. Uribe ◽  
H. Folch ◽  
R. Enriquez ◽  
G. Moran
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Extended Period ◽  
Innate Immune ◽  
Acquired Immunity ◽  
Free Living ◽  
Humoral Factors ◽  
Innate And Adaptive Immunity ◽  
Living Organisms ◽  
Aquaculture Production

  The immune system of fish is very similar to vertebrates, although there are some important differences. Fish are free-living organisms from the embryonic stage of life in their aquatic environment. They have mechanisms to protect themselves from a wide variety of microorganisms. Consequently, fish rely on their innate immune system for an extended period of time, beginning at the early stages of embryogenesis. The components of the innate immune response are divided into physical, cellular and humoral factors and include humoral and cellular receptor molecules that are soluble in plasma and other body fluids. The lymphoid organs found in fish include the thymus, spleen and kidney. Immunoglobulins are the principal components of the immune response against pathogenic organisms. Immunomodulatory products, including nucleotides, glucans and probiotics, are increasingly used in aquaculture production. The use of these products reduces the need for therapeutic treatments, enhances the effects of vaccines and, in turn, improves the indicators of production. The aim of this review is to provide a review of the immune system in fish, including the ontogeny, mechanisms of unspecific and acquired immunity and the action of some immunomodulators.

scholarly journals Bacterial lipids: powerful modifiers of the innate immune response

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 1334 ◽  
Author(s):  
Courtney E. Chandler ◽  
Robert K. Ernst
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Innate Immune Response ◽  
Lipoteichoic Acid ◽  
Innate Immune ◽  
Microbial Pathogens ◽  
Host Immune System ◽  
Receptor Proteins ◽  
Bacterial Membranes ◽  
Host Innate Immune Response

The innate immune system serves as a first line of defense against microbial pathogens. The host innate immune response can be triggered by recognition of conserved non-self-microbial signature molecules by specific host receptor proteins called Toll-like receptors. For bacteria, many of these molecular triggers reside on or are embedded in the bacterial membrane, the interface exposed to the host environment. Lipids are the most abundant component of membranes, and bacteria possess a unique set of lipids that can initiate or modify the host innate immune response. Bacterial lipoproteins, peptidoglycan, and outer membrane molecules lipoteichoic acid and lipopolysaccharide are key modulators of the host immune system. This review article will highlight some of the research emerging at the crossroads of bacterial membranes and innate immunity.

scholarly journals Unity, Continuity, Structure, and Function. The Ongoing Search for a Deeper Understanding of the Many Roles Attributed to Fascia in the Living Human Body - An Osteopathic Perspective

2020 ◽  
Vol 06 (03) ◽  
pp. 1-1
Author(s):  
Colin Armstrong ◽  
Keyword(s):  
Human Body ◽  
The Body ◽  
Human Form ◽  
In Situ Methods ◽  
Living Organisms ◽  
The Many ◽  
And Function ◽  
Dynamic Interplay

Progress in technologies, notably in vivo and in situ methods, has equipped scientists with the necessary skills to explore the living human body in increasingly minute detail. This has led to a better understanding of the dynamic interplay between the various elements that make up the living human body. To further understand the interplay, this research focuses on the insights and observations of the founders of osteopathy, who placed great importance on the role of fascia in the body. Modern anatomical investigation still relies heavily on dissection to describe the structural organization of living organisms. Therefore, at present, a major challenge faced by modern anatomists is to move towards a more holistic and integrative understanding of the unity, continuity, and dynamic interplay between the various elements that come together to create the living human form.

Discovery of novel antimicrobial peptides: A transcriptomic study of the sea anemone Cnidopus japonicus

2018 ◽  
Vol 16 (02) ◽  
pp. 1840006 ◽  
Author(s):  
Ekaterina N. Grafskaia ◽  
Nadezhda F. Polina ◽  
Vladislav V. Babenko ◽  
Daria D. Kharlampieva ◽  
Pavel A. Bobrovsky ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Antimicrobial Peptides ◽  
Search Algorithm ◽  
Sea Anemone ◽  
Amino Acid Sequences ◽  
Innate Immune ◽  
Bacterial Strains ◽  
Wide Range ◽  
Structural Peculiarities ◽  
Living Organisms

As essential conservative component of the innate immune systems of living organisms, antimicrobial peptides (AMPs) could complement pharmaceuticals that increasingly fail to combat various pathogens exhibiting increased resistance to microbial antibiotics. Among the properties of AMPs that suggest their potential as therapeutic agents, diverse peptides in the venoms of various predators demonstrate antimicrobial activity and kill a wide range of microorganisms. To identify potent AMPs, the study reported here involved a transcriptomic profiling of the tentacle secretion of the sea anemone Cnidopus japonicus. An in silico search algorithm designed to discover toxin-like proteins containing AMPs was developed based on the evaluation of the properties and structural peculiarities of amino acid sequences. The algorithm revealed new proteins of the anemone containing antimicrobial candidate sequences, and 10 AMPs verified using high-throughput proteomics were synthesized. The antimicrobial activity of the candidate molecules was experimentally estimated against Gram-positive and -negative bacteria. Ultimately, three peptides exhibited antimicrobial activity against bacterial strains, which suggests that the method can be applied to reveal new AMPs in the venoms of other predators as well.

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