The field of medical diagnostics and therapeutics is being revolutionized by nanotechnology, from targeted drug delivery to cancer immunotherapy. Inorganic nanoparticles are widely used, albeit ...problems with agglutination, cytotoxicity, free radical generation, and instability in some biological environments limits their utility. Conjugation of biomolecules such as peptides to the surface of nanoparticles can mitigate such problems, as well as confer specialized theranostic (therapeutic and/or diagnostic) properties, useful across biomedical applications such as vaccines, drug delivery, and in vivo imaging. Coating with amino acids, rather than peptides, offers further a highly cost-effective approach (due to their ease of purification and availability), but is currently an underutilized way to decrease toxicity and enhance stability. Amino acid molecules are small (<200 Da) and have both positive and negative charge groups (zwitterionic) facilitating charge-specific molecule binding. Additionally, amino acids exert by themselves some useful biological functions, with antibacterial and viability enhancing properties (for eukaryotic cells). Overall particle size, nanoparticle core, and the specific amino acid used to functionalize their surface influence their biodistribution, and their effects on host immunity. In this review, we provide for the first time an overview of this emerging field, and identify gaps in knowledge for future research.
Tumor necrosis factor-alpha (TNF) is a pleiotropic cytokine, which is thought to play a major role in the pathogenesis of inflammatory diseases, including allergy. TNF is produced at the early stage ...of allergen sensitization, and then continues to promote the inflammation cascade in the effector phase of allergic reactions. Consequently, anti-TNF treatment has been proposed as a potential therapeutic option. However, recent studies reveal anti-intuitive effects of TNF in the activation and proliferative expansion of immunosuppressive Tregs, tolerogenic DCs and MDSCs. This immunosuppressive effect of TNF is mediated by TNFR2, which is preferentially expressed by immunosuppressive cells. These findings redefine the role of TNF in allergic reaction, and suggest that targeting TNF-TNFR2 interaction itself may represent a novel strategy in the treatment of allergy.
The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has recently emerged in China and caused a disease called coronavirus disease 2019 (COVID-19). The virus quickly spread around the ...world, causing a sustained global outbreak. Although SARS-CoV-2, and other coronaviruses, SARS-CoV and Middle East respiratory syndrome CoV (MERS-CoV) are highly similar genetically and at the protein production level, there are significant differences between them. Research has shown that the structural spike (S) protein plays an important role in the evolution and transmission of SARS-CoV-2. So far, studies have shown that various genes encoding primarily for elements of S protein undergo frequent mutation. We have performed an in-depth review of the literature covering the structural and mutational aspects of S protein in the context of SARS-CoV-2, and compared them with those of SARS-CoV and MERS-CoV. Our analytical approach consisted in an initial genome and transcriptome analysis, followed by primary, secondary and tertiary protein structure analysis. Additionally, we investigated the potential effects of these differences on the S protein binding and interactions to angiotensin-converting enzyme 2 (ACE2), and we established, after extensive analysis of previous research articles, that SARS-CoV-2 and SARS-CoV use different ends/regions in S protein receptor-binding motif (RBM) and different types of interactions for their chief binding with ACE2. These differences may have significant implications on pathogenesis, entry and ability to infect intermediate hosts for these coronaviruses. This review comprehensively addresses in detail the variations in S protein, its receptor-binding characteristics and detailed structural interactions, the process of cleavage involved in priming, as well as other differences between coronaviruses.
Carnosine is a dipeptide molecule (β-alanyl-l-histidine) with anti-inflammatory, antioxidant, anti-glycation, and chelating properties. It is used in exercise physiology as a food supplement to ...increase performance; however, in vitro evidence suggests that carnosine may exhibit anti-cancer properties.
In this study, we investigated the effect of carnosine on breast, ovarian, colon, and leukemic cancer cell proliferation. We further examined U937 promonocytic, human myeloid leukemia cell phenotype, gene expression, and cytokine secretion to determine if these are linked to carnosine's anti-proliferative properties.
Carnosine (1) inhibits breast, ovarian, colon, and leukemic cancer cell proliferation; (2) upregulates expression of pro-inflammatory molecules; (3) modulates cytokine secretion; and (4) alters U937 differentiation and phenotype.
These effects may have implications for a role for carnosine in anti-cancer therapy.
Stingless bees are a type of honey producers that commonly live in tropical countries. Their use for honey is being abandoned due to its limited production. However, the recent improvements in ...stingless bee honey production, particularly in South East Asia, have brought stingless bee products back into the picture. Although there are many stingless bee species that produce a wide spread of products, known since old eras in traditional medicine, the modern medical community is still missing more investigational studies on stingless bee products. Whereas comprehensive studies in the current era attest to the biological and medicinal properties of honeybee (
) products, the properties of stingless bee products are less known. This review highlights for the first time the medicinal benefits of stingless bee products (honey, propolis, pollen and cerumen), recent investigations and promising future directions. This review emphasizes the potential antioxidant properties of these products that in turn play a vital role in preventing and treating diseases associated with oxidative stress, microbial infections and inflammatory disorders. Summarizing all these data and insights in one manuscript may increase the commercial value of stingless bee products as a food ingredient. This review will also highlight the utility of stingless bee products in the context of medicinal and therapeutic properties, some of which are yet to be discovered.
To be optimally effective, peptide-based vaccines need to be administered with adjuvants. Many currently available adjuvants are toxic, not biodegradable; they invariably invoke adverse reactions, ...including allergic responses and excessive inflammation. A nontoxic, biodegradable, biocompatible, self-adjuvanting vaccine delivery system is urgently needed. Herein, we report a potent vaccine delivery system fulfilling the above requirements. A peptide antigen was coupled with poly-hydrophobic amino acid sequences serving as self-adjuvanting moieties using solid-phase synthesis, to produce fully defined single molecular entities. Under aqueous conditions, these molecules self-assembled into distinct nanoparticles and chain-like aggregates. Following subcutaneous immunization in mice, these particles successfully induced opsonic epitope-specific antibodies without the need of external adjuvant. Mice immunized with entities bearing 15 leucine residues were able to clear bacterial load from target organs without triggering the release of soluble inflammatory mediators. Thus, we have developed a well-defined and effective self-adjuvanting delivery system for peptide antigens.
There is great interest in developing efficient therapeutic cancer vaccines, as this type of therapy allows targeted killing of tumor cells as well as long-lasting immune protection. High levels of ...tumor-infiltrating CD8
T cells are associated with better prognosis in many cancers, and it is expected that new generation vaccines will induce effective production of these cells. Epigenetic mechanisms can promote changes in host immune responses, as well as mediate immune evasion by cancer cells. Here, we focus on epigenetic modifications involved in both vaccine-adjuvant-generated T cell immunity and cancer immune escape mechanisms. We propose that vaccine-adjuvant systems may be utilized to induce beneficial epigenetic modifications and discuss how epigenetic interventions could improve vaccine-based therapies. Additionally, we speculate on how, given the unique nature of individual epigenetic landscapes, epigenetic mapping of cancer progression and specific subsequent immune responses, could be harnessed to tailor therapeutic vaccines to each patient.
During COVID-19 lockdowns, online learning activities had to be developed for the Undergraduate and Masters by Coursework Bioinformatics students at RMIT University. Therefore, we designed an ...integrative, industry-based research assignment, which guided the students through a drug discovery project from target identification to lead optimization. The students were able to utilize this real-life scenario to apply multiple diverse but complementary bioinformatic principles to analyze biological and chemical data leading to meaningful predictions. This activity was utilized as a final assessment of the students’ knowledge.
•Dead sludge biomass skewed DNA-based functional predictions for anaerobic digestion.•PMA-seq is a promising approach for assessing the active biomass of anaerobic sludge.•Potential predictive value ...of dead-biomass DNA for process-relevant metabolites.•Two universal primer candidates for amplicon sequencing of anaerobic sludge.
DNA-based monitoring of microbial communities that are responsible for the performance of anaerobic digestion of sewage wastes has the potential to improve resource recoveries for wastewater treatment facilities. By treating sludge with propidium monoazide (PMA) prior to amplicon sequencing, this study explored how the presence of DNA from dead microbial biomass carried over with feed sludge may mislead process-relevant biomarkers, and whether primer choice impacts such assessments. Four common primers were selected for amplicon preparation, also to determine if universal primers have sufficient taxonomic or functional coverage for monitoring ecological performance; or whether two domain-specific primers for Bacteria and Archaea are necessary. Anaerobic sludges of three municipal continuously stirred-tank reactors in Victoria, Australia, were sampled at one time-point. A total of 240 amplicon libraries were sequenced on a Miseq using two universal and two domain-specific primer pairs. Untargeted metabolomics was chosen to complement biological interpretation of amplicon gene-based functional predictions. Diversity, taxonomy, phylogeny and functional potentials were systematically assessed using PICRUSt2, which can predict community wide pathway abundance. The two chosen universal primers provided similar diversity profiles of abundant Bacteria and Archaea, compared to the domain-specific primers. About 16 % of all detected prokaryotic genera covering 30 % of total abundances and 6 % of PICRUSt2-estimated pathway abundances were affected by PMA. This showed that dead biomass in the anaerobic digesters impacted DNA-based assessments, with implications for predicting active processes, such as methanogenesis, denitrification or the identification of organisms associated with biological foams. Hence, instead of running two sequencing runs with two different domain-specific primers, we propose conducting PMA-seq with universal primer pairs for routine performance monitoring. However, dead sludge biomass may have some predictive value. In principal component analysis the compositional variation of 239 sludge metabolites resembled that of 'dead-plus-alive' biomass, suggesting that dead organisms contributed to the potentially process-relevant sludge metabolome.
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Antigens incorporated in subunit vaccines are typically poorly immunogenic, so a strong immunostimulant (adjuvant) and/or delivery system is required to boost immunogenicity. In this work, the ...various functional polymer nanostructures, that is, rods, worms, spheres, and tadpoles are used to develop potent peptide antigen delivery systems. The antigen PADRE‐J8 (PJ8), derived from Group A Streptococcus (GAS) M‐protein, is either physically mixed or chemically conjugated to polymeric nanoparticles of different shapes. The physical mixture of polymeric nanoparticles and antigen is more effective in inducing antibody production than their chemical conjugates. Moreover, rod‐shaped polymeric nanoparticles in physical mixture with PJ8 elicited higher and more opsonic antibody titers than powerful complete Freund's adjuvant (CFA)‐adjuvanted antigen. Herein, for the first time it is demonstrated that a) the block copolymer, in nanoparticle form, can act as an immune adjuvant, b) nanoparticle shape plays a crucial role in their immunogenicity, and c) antigen conjugation is not required, nor is antigen encapsulation or absorption.
It is demonstrated that a) the block copolymer, in nanoparticle form, can act as an immune adjuvant, b) nanoparticle shape plays a crucial role in their immunogenicity, c) the physical mixture of polymeric nanoparticles and antigen is more effective in inducing antibody production than their chemical conjugates, and d) antigen encapsulation or absorption on nanoparticles is not required.
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