Are Long-Chain Polyunsaturated Fatty Acids the Link between the Immune System and the Microbiome towards Modulating Cancer?

Three recent studies revealed synergy between immune-checkpoint inhibitors and the microbiome as a new approach in the treatment of cancer. Incidentally, there has been significant progress in understanding the role of polyunsaturated fatty acids (PUFAs) in modulating cancer and the immune system, as well as in regulating the microbiome. Inflammation seems to be the common denominator among these seemingly unrelated biological entities-immune system, the microbiome, and long-chain polyunsaturated fatty acids (LC-PUFAs).

A pilot single centre, double blind, placebo controlled, randomized, parallel study of Calmagen® dermaceutical cream and lotion for the topical treatment of tinea and onychomycosis.

Background: Most of the current anti-fungal treatments are chemical-based, fungistatic, have low efficacy in the treatment of tinea and toxicity concerns, while onychomycosis remains recalcitrant to most antifungal therapies. The study aimed to establish the fungicidal, efficacy and safety profile of Calmagen® dermaceutical cream and lotion containing AMYCOT® as a topical treatment in patients with severe to very severe presentations of fungal skin (tinea) and nail infections (onychomycosis).

Methods: A randomized, placebo-controlled, double blind, parallel, single centre study was conducted on 28 subjects with severe to very severe tinea or onychomycosis.

Generation of a Novel Bacteriophage Library Displaying scFv Antibody Fragments from the Natural Buffalo Host to Identify Antigens from Adult Schistosoma japonicum for Diagnostic Development.

The development of effective diagnostic tools will be essential in the continuing fight to reduce schistosome infection; however, the diagnostic tests available to date are generally laborious and difficult to implement in current parasite control strategies. We generated a series of single-chain antibody Fv domain (scFv) phage display libraries from the portal lymph node of field exposed water buffaloes, Bubalus bubalis, 11-12 days post challenge with Schistosoma japonicum cercariae. The selected scFv-phages showed clear enrichment towards adult schistosomes and excretory-secretory (ES) proteins by immunofluorescence, ELISA and western blot analysis.

Postprandial insulin and glucose levels are reduced in healthy subjects when a standardised breakfast meal is supplemented with a filtered sugarcane molasses concentrate.

Purpose: A phytochemical- and mineral-rich filtered sugarcane molasses concentrate (FMC), when added to carbohydrate-containing foods as a functional ingredient, lowers postprandial blood glucose and insulin responses. We hypothesised that this beneficial effect would also occur if FMC was administered as an oral supplement taken before a meal.

Methods: This study measured the postprandial glucose and insulin responses elicited by different doses of FMC administered immediately prior to a standard breakfast to healthy subjects.

Using the local immune response from the natural buffalo host to generate an antibody fragment library that binds the early larval stages of Schistosoma japonicum.

Antibodies isolated from the local draining inguinal lymph node of field exposed-water buffaloes following challenge with Schistosoma japonicum cercariae showed high reactivity towards S. japonicum antigen preparations and bound specifically to formaldehyde-fixed S. japonicum schistosomules.

Filtered molasses concentrate from sugar cane: natural functional ingredient effective in lowering the glycaemic index and insulin response of high carbohydrate foods.

An aqueous filtered molasses concentrate (FMC) sourced from sugar cane was used as a functional ingredient in a range of carbohydrate-containing foods to reduce glycaemic response. When compared to untreated controls, postprandial glucose responses in the test products were reduced 5-20%, assessed by accredited glycaemic index (GI) testing. The reduction in glucose response in the test foods was dose-dependent and directly proportional to the ratio of FMC added to the amount of available carbohydrate in the test products.

The anti-cancer IgM monoclonal antibody PAT-SM6 binds with high avidity to the unfolded protein response regulator GRP78.

The monoclonal IgM antibody PAT-SM6 derived from human tumours induces apoptosis in tumour cells and is considered a potential anti-cancer agent. A primary target for PAT-SM6 is the unfolded protein response regulator GRP78, over-expressed externally on the cell surface of tumour cells. Small angle X-ray scattering (SAXS) studies of human GRP78 showed a two-domain dumbbell-shaped monomer, while SAXS analysis of PAT-SM6 revealed a saucer-shaped structure accommodating five-fold symmetry, consistent with previous studies of related proteins.

Immunoglobulin M as a vaccine adjuvant.

Vaccines are effective in preventing disease by stimulating the immune system and sustaining an immune response towards eradication of pathogens and diseased cells. However, designing successful vaccines is not always straightforward. For a vaccine to be successful, antigen-presenting cells (APC) need to be stimulated, primarily by adjuvants, towards a sustained immune response through integration of the innate and adaptive (humoral and cellular) immune systems.

High level expression of functional human IgMs in human PER.C6 cells.

Natural IgM antibodies play an important role in the body's defense mechanisms against transformed cells in the human body and are currently being exploited both in prognoses of malignant lesions and in the therapy of cancer patients. However, despite growing interest and clinical promise, thus far the IgM class of antibodies has failed to gain widespread commercial interest as these are considered to be difficult to produce recombinantly. IgMs are polymeric and have a relatively large mass.

Protein depletion using IgY from chickens immunised with human protein cocktails.

Given that proteomic analysis of complex protein mixtures may be restricted by the presence of highly abundant proteins, sample preparation to remove abundant proteins is essential for the analysis of low abundance proteins. Chickens are effective producers of antibodies (IgY) against mammalian proteins, able to produce large quantities of antibodies that can be recovered by simple non-intrusive extraction of egg yolk. The extraction procedure described uses a modification of the water dilution method (WD) to deplete lipids and lipoproteins followed by sequential precipitation with 31% ammonium sulphate and 12% poly ethylene glycol (PEG) producing IgY antibodies with greater than 95% purity and no loss in immunoreactivity.

Cryptic protein fragments as an emerging source of peptide drugs.

This commentary evaluates the newly proposed concept of crypteins - peptides with embedded cryptic activity - as a source of peptide drugs. Although several crypteins are undergoing advanced clinical trials, and one cryptein, adrenocorticotropic hormone (ACTH), is already widely used as a therapeutic, crypteins remain an underappreciated class of biopharmaceuticals. The systematic exploitation of crypteins provides a novel source of peptide drugs, and may also provide templates for developing peptidomimetic compounds.

The cryptome: a subset of the proteome, comprising cryptic peptides with distinct bioactivities.

There is increasing evidence that proteolytic cleavage gives rise to 'hidden' peptides with bioactivities that are often unpredicted and totally distinct to the parent protein. So far, the liberation of these cryptic peptides, or crypteins, has been shown to be prevalent in proteins associated with endocrine signalling, the extracellular matrix, the complement cascade and milk. A broad spectrum of proteases has been implicated in the generation of natural crypteins that appear to play a role in modulating diverse biological processes, such as angiogenesis, immune function and cell growth.

Functional proteomic screens in therapeutic protein drug discovery.

Biopharmaceuticals, mainly protein-based therapeutics, are rapidly being developed for several disease indications. However, most biopharmaceuticals are 'me-too' drugs or are being developed against the same handful of targets. Thus, the potential of biopharmaceuticals is not being fully exploited.

Functional proteomic screen identifies a modulating role for CD44 in death receptor-mediated apoptosis.

Apoptotic evasion is a hallmark of cancer and its resistance to chemotherapeutic drugs. Identification of cellular proteins that mediate apoptotic programs is a critical step toward the development of therapeutics aimed at overcoming apoptosis resistance. We developed an innovative high-throughput screen to identify proteins that modulate Fas ligand-mediated apoptosis using fluorophore-assisted light inactivation (HTS-FALIpop).

CD155/PVR plays a key role in cell motility during tumor cell invasion and migration.

Background: Invasion is an important early step of cancer metastasis that is not well understood. Developing therapeutics to limit metastasis requires the identification and validation of candidate proteins necessary for invasion and migration.

Methods: We developed a functional proteomic screen to identify mediators of tumor cell invasion.

Developments in modulating protein function for effective target validation.

The targets of more than 95% of clinically approved drugs are proteins. Thus, the plethora of targets derived from genomics and proteomics efforts must be validated at the protein level. However, most of the preferred target validation technologies are gene- or transcript-based.

Functional proteomic screens reveal an essential extracellular role for hsp90 alpha in cancer cell invasiveness.

Tumour cell invasiveness is crucial for cancer metastasis and is not yet understood. Here we describe two functional screens for proteins required for the invasion of fibrosarcoma cells that identified the molecular chaperone heat shock protein 90 (hsp90). The hsp90 alpha isoform, but not hsp90 beta, is expressed extracellularly where it interacts with the matrix metalloproteinase 2 (MMP2).

Biochips beyond DNA: technologies and applications.

Technological advances in miniaturization have found a niche in biology and signal the beginning of a new revolution. Most of the attention and advances have been made with DNA chips yet a lot of progress is being made in the use of other biomolecules and cells. A variety of reviews have covered only different aspects and technologies but leading to the shared terminology of "biochips.

Direct methods for modulating protein function.

During the past few years, the drug discovery process has shifted from a chemistry- to a biology-driven paradigm. Genome sciences have made a significant contribution to this shift, leading to a plethora of potential drug targets that are mainly proteins. Genetic methods will continue to be used to characterize proteins, but more direct methods are needed to determine the suitability of these protein targets for pharmacological intervention.

Emerging high-throughput drug target validation technologies.

Identifying the right target for drug development is a critical bottleneck in the pharmaceutical and biotech industries. The genomics revolution has shifted the problem from a scarcity of targets to a surplus of putative drug targets. As the validity of a target cannot be simply inferred from correlative data, the key is confirmation of the causative role of a gene product in a particular disease.

Biomedical applications of protein chips.

The development of microchips involving proteins has accelerated within the past few years. Although DNA chip technologies formed the precedent, many different strategies and technologies have been used because proteins are inherently a more complex type of molecule. This review covers the various biomedical applications of protein chips in diagnostics, drug screening and testing, disease monitoring, drug discovery (proteomics), and medical research.