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Toxins Sep 2023Vaccines are one of the most effective strategies to prevent pathogen-induced illness in humans. The earliest vaccines were based on live inoculations with low doses of... (Review)
Review
Vaccines are one of the most effective strategies to prevent pathogen-induced illness in humans. The earliest vaccines were based on live inoculations with low doses of live or related pathogens, which carried a relatively high risk of developing the disease they were meant to prevent. The introduction of attenuated and killed pathogens as vaccines dramatically reduced these risks; however, attenuated live vaccines still carry a risk of reversion to a pathogenic strain capable of causing disease. This risk is completely eliminated with recombinant protein or subunit vaccines, which are atoxic and non-infectious. However, these vaccines require adjuvants and often significant optimization to induce robust T-cell responses and long-lasting immune memory. Some pathogens produce protein toxins that cause or contribute to disease. To protect against the effects of such toxins, chemically inactivated toxoid vaccines have been found to be effective. Toxoid vaccines are successfully used today at a global scale to protect against tetanus and diphtheria. Recent developments for toxoid vaccines are investigating the possibilities of utilizing recombinant protein toxins mutated to eliminate biologic activity instead of chemically inactivated toxins. Finally, one of the most contemporary approaches toward vaccine design utilizes messenger RNA (mRNA) as a vaccine candidate. This approach was used globally to protect against coronavirus disease during the COVID-19 pandemic that began in 2019, due to its advantages of quick production and scale-up, and effectiveness in eliciting a neutralizing antibody response. Nonetheless, mRNA vaccines require specialized storage and transport conditions, posing challenges for low- and middle-income countries. Among multiple available technologies for vaccine design and formulation, which technology is most appropriate? This review focuses on the considerable developments that have been made in utilizing diverse vaccine technologies with a focus on vaccines targeting bacterial toxins. We describe how advancements in vaccine technology, combined with a deeper understanding of pathogen-host interactions, offer exciting and promising avenues for the development of new and improved vaccines.
Topics: Humans; Pandemics; COVID-19; Vaccines, Attenuated; Vaccines, Synthetic; Toxins, Biological; Bacterial Vaccines; Tetanus Toxoid
PubMed: 37755989
DOI: 10.3390/toxins15090563 -
Molecular Biology Reports Dec 2023The increase in bacterial resistance generated by the indiscriminate use of antibiotics in medical practice set new challenges for discovering bioactive natural products... (Review)
Review
The increase in bacterial resistance generated by the indiscriminate use of antibiotics in medical practice set new challenges for discovering bioactive natural products as alternatives for therapeutics. Lanthipeptides are an attractive natural product group that has been only partially explored and shows engaging biological activities. These molecules are small peptides with potential application as therapeutic agents. Some members show antibiotic activity against problematic drug-resistant pathogens and against a wide variety of viruses. Nevertheless, their biological activities are not restricted to antimicrobials, as their contribution to the treatment of cystic fibrosis, cancer, pain symptoms, control of inflammation, and blood pressure has been demonstrated. The study of biosynthetic gene clusters through genome mining has contributed to accelerating the discovery, enlargement, and diversification of this group of natural products. In this review, we provide insight into the recent advances in the development and research of actinobacterial lanthipeptides that hold great potential as therapeutics.
Topics: Humans; Anti-Bacterial Agents; Peptides; Biological Products; Multigene Family; Bacterial Infections
PubMed: 37934370
DOI: 10.1007/s11033-023-08880-w -
Journal of Chemical Information and... Sep 2023The therapeutic approach of targeted protein degradation (TPD) is gaining momentum due to its potentially superior effects compared with protein inhibition. Recent... (Review)
Review
The therapeutic approach of targeted protein degradation (TPD) is gaining momentum due to its potentially superior effects compared with protein inhibition. Recent advancements in the biotech and pharmaceutical sectors have led to the development of compounds that are currently in human trials, with some showing promising clinical results. However, the use of computational tools in TPD is still limited, as it has distinct characteristics compared with traditional computational drug design methods. TPD involves creating a ternary structure (protein-degrader-ligase) responsible for the biological function, such as ubiquitination and subsequent proteasomal degradation, which depends on the spatial orientation of the protein of interest (POI) relative to E2-loaded ubiquitin. Modeling this structure necessitates a unique blend of tools initially developed for small molecules (e.g., docking) and biologics (e.g., protein-protein interaction modeling). Additionally, degrader molecules, particularly heterobifunctional degraders, are generally larger than conventional small molecule drugs, leading to challenges in determining drug-like properties like solubility and permeability. Furthermore, the catalytic nature of TPD makes occupancy-based modeling insufficient. TPD consists of multiple interconnected yet distinct steps, such as POI binding, E3 ligase binding, ternary structure interactions, ubiquitination, and degradation, along with traditional small molecule properties. A comprehensive set of tools is needed to address the dynamic nature of the induced proximity ternary complex and its implications for ubiquitination. In this Perspective, we discuss the current state of computational tools for TPD. We start by describing the series of steps involved in the degradation process and the experimental methods used to characterize them. Then, we delve into a detailed analysis of the computational tools employed in TPD. We also present an integrative approach that has proven successful for degrader design and its impact on project decisions. Finally, we examine the future prospects of computational methods in TPD and the areas with the greatest potential for impact.
Topics: Humans; Proteolysis; Biological Products; Catalysis; Drug Design; Permeability
PubMed: 37602861
DOI: 10.1021/acs.jcim.3c00603 -
Scientific Reports Oct 2023Joint inhumations of adults and children are an intriguing aspect of the shift from collective to single burial rites in third millennium BC Western Eurasia. Here, we...
Joint inhumations of adults and children are an intriguing aspect of the shift from collective to single burial rites in third millennium BC Western Eurasia. Here, we revisit two exceptional Beaker period adult-child graves using ancient DNA: Altwies in Luxembourg and Dunstable Downs in Britain. Ancestry modelling and patterns of shared IBD segments between the individuals examined, and contemporary genomes from Central and Northwest Europe, highlight the continental connections of British Beakers. Although simultaneous burials may involve individuals with no social or biological ties, we present evidence that close blood relations played a role in shaping third millennium BC social systems and burial practices, for example a biological mother and her son buried together at Altwies. Extended family, such as a paternal aunt at Dunstable Downs, could also act as 'substitute parents' in the grave. Hypotheses are explored to explain such simultaneous inhumations. Whilst intercommunity violence, infectious disease and epidemics may be considered as explanations, they fail to account for both the specific, codified nature of this particular form of inhumation, and its pervasiveness, as evidenced by a representative sample of 131 adult-child graves from 88 sites across Eurasia, all dating to the third and second millennia BC.
Topics: Humans; Adult; Female; Archaeology; Burial; Europe; Parents; Adult Children
PubMed: 37907573
DOI: 10.1038/s41598-023-45612-3 -
Human Vaccines & Immunotherapeutics Dec 2023In the field of immunology, a systems biology approach is crucial to understanding the immune response to infection and vaccination considering the complex interplay... (Review)
Review
In the field of immunology, a systems biology approach is crucial to understanding the immune response to infection and vaccination considering the complex interplay between genetic, epigenetic, and environmental factors. Significant progress has been made in understanding the innate immune response, including cell players and critical signaling pathways, but many questions remain unanswered, including how the innate immune response dictates host/pathogen responses and responses to vaccines. To complicate things further, it is becoming increasingly clear that the innate immune response is not a linear pathway but is formed from complex networks and interactions. To further our understanding of the crosstalk and complexities, systems-level analyses and expanded experimental technologies are now needed. In this review, we discuss the most recent immunoprofiling techniques and discuss systems approaches to studying the global innate immune landscape which will inform on the development of personalized medicine and innovative vaccine strategies.
Topics: Vaccines; Immunity, Innate; Vaccination; Systems Biology
PubMed: 37885158
DOI: 10.1080/21645515.2023.2267295 -
International Journal of Molecular... Feb 2024Black garlic (BG) is a fermented form of garlic (.), produced at precisely defined temperatures, humidities, and time periods. Although garlic has been used for... (Review)
Review
Black garlic (BG) is a fermented form of garlic (.), produced at precisely defined temperatures, humidities, and time periods. Although garlic has been used for thousands of years, black garlic is a relatively new discovery. There are many bioactive compounds in black garlic that give it medicinal properties, including anti-inflammatory and anti-cancer properties. In our review article, we present scientific studies examining the anti-inflammatory and anti-cancer effects of black garlic. According to research, this effect is mainly due to the reduction in the production of pro-inflammatory cytokines, as well as the ability to scavenge free oxygen radicals and induce apoptosis. In addition, the phytochemicals contained in it have antiproliferative and antiangiogenic properties and inhibit the growth of cancer cells. Black garlic is a valuable source of biologically active substances that can support anti-inflammatory and anti-cancer therapy. Compared to black garlic has fewer side effects and is easier to consume.
Topics: Humans; Garlic; Plant Extracts; Antioxidants; Neoplasms; Anti-Inflammatory Agents; Biological Products
PubMed: 38339077
DOI: 10.3390/ijms25031801 -
Platelets Dec 2023Besides their proteome, platelets use, in all responses to the environmental cues, a huge and diverse family of hydrophobic and amphipathic small molecules involved in...
Besides their proteome, platelets use, in all responses to the environmental cues, a huge and diverse family of hydrophobic and amphipathic small molecules involved in structural, metabolic and signaling functions; the lipids. Studying how platelet lipidome changes modulate platelet function is an old story constantly renewed through the impressive technical advances allowing the discovery of new lipids, functions and metabolic pathways. Technical progress in analytical lipidomic profiling by top-of-the-line approaches such as nuclear magnetic resonance and gas chromatography or liquid chromatography coupled to mass spectrometry enables either large-scale analysis of lipids or targeted lipidomics. With the support of bioinformatics tools and databases, it is now possible to investigate thousands of lipids over a concentration range of several orders of magnitude. The lipidomic landscape of platelets is considered a treasure trove, not only able to expand our knowledge of platelet biology and pathologies but also to bring diagnostic and therapeutic opportunities. The aim of this commentary article is to summarize the advances in the field and to highlight what lipidomics can tell us about platelet biology and pathophysiology.
Topics: Humans; Lipidomics; Blood Platelets; Chromatography, Liquid; Computational Biology; Lipids
PubMed: 36880158
DOI: 10.1080/09537104.2023.2182180 -
Nutrients Sep 2023L. (commonly known as bog bilberry) and L. (commonly known as bilberry) are species of the genus (family ). The red-purple-blue coloration of blueberries is... (Review)
Review
L. (commonly known as bog bilberry) and L. (commonly known as bilberry) are species of the genus (family ). The red-purple-blue coloration of blueberries is attributed largely to the anthocyanins found in bilberries. Anthocyanins, known for their potent biological activity as antioxidants, have a significant involvement in the prophylaxis of cancer or other diseases, including those of metabolic origin. Bilberry is the most important economically wild berry in Northern Europe, and it is also extensively used in juice and food production. A review of the latest literature was performed to assess the composition and biological activity of and . Clinical studies confirm the benefits of and supplementation as part of a healthy diet. Because of their antioxidant, anti-inflammatory, anti-cancer, and apoptosis-reducing activity, both bog bilberries and bilberries can be used interchangeably as a dietary supplement with anti-free radical actions in the prevention of cancer diseases and cataracts, or as a component of sunscreen preparations.
Topics: Vaccinium myrtillus; Blueberry Plants; Anthocyanins; Functional Food; Fruit; Antioxidants; Plant Extracts
PubMed: 37836403
DOI: 10.3390/nu15194119 -
Annual Review of Entomology Jan 2024Earwigs are often known for the forceps-like appendage at the end of their abdomen, urban legends about them crawling into human ears, and their roles as pest and... (Review)
Review
Earwigs are often known for the forceps-like appendage at the end of their abdomen, urban legends about them crawling into human ears, and their roles as pest and biological control agents. However, they are much less known for their social life. This is surprising, as many of the 1,900 species of earwigs show social behaviors toward eggs, juveniles, and adults. These behaviors typically occur during family and group living, which may be obligatory or facultative, last up to several months, and involve only a few to several hundred related or unrelated individuals. Moreover, many individuals can alternate between solitary and group living during their life cycle, an ability that probably prevailed during the emergence of social life. In this review, I detail the diversity of group living and social behavior in earwigs and show how further developing this knowledge in Dermaptera can improve our general understanding of the early evolution of social life in insects.
Topics: Animals; Humans; Social Behavior; Biology
PubMed: 37722682
DOI: 10.1146/annurev-ento-013023-015632 -
Biomolecules Jul 2023is known for its ability to produce numerous bioactive natural products, making it valuable in drug development. This review provides information on the sources,... (Review)
Review
is known for its ability to produce numerous bioactive natural products, making it valuable in drug development. This review provides information on the sources, distribution, chemical structure types, biosynthesis, and biological activities of the compounds isolated from the genus in the family from 1969 to 2022. The results show that 50% of the compounds isolated from are new natural products, and 82% of the natural products derived from this genus are from the marine . The compounds isolated from exhibit diverse structures, with alkaloids being of particular importance, accounting for 56% of the natural products derived from this genus. Furthermore, within the alkaloid class, 61% belong to the epipolythiodioxopiperazine family, highlighting the significance of epipolythiodioxopiperazine as a key characteristic structure within . Seventy-two percent of natural products derived from display bioactivities, with 50% of the bioactive compounds exhibiting more significant or comparable activities than their positive controls. Interestingly, 89% of potent active compounds are derived from marine fungi, demonstrating their promising potential for development. These findings underscore , particularly the marine-derived genus , a valuable source of new bioactive secondary metabolites, and emphasize the vast resource importance of the ocean.
Topics: Ascomycota; Biological Products; Drug Development
PubMed: 37627256
DOI: 10.3390/biom13081191