It is time to shift the arachidonic acid (ARA) paradigm from a harm-generating molecule to its status of polyunsaturated fatty acid essential for normal health. ARA is an integral constituent of biological cell membrane, conferring it with fluidity and flexibility, so necessary for the function of all cells, especially in nervous system, skeletal muscle, and immune system. Arachidonic acid is obtained from food or by desaturation and chain elongation of the plant-rich essential fatty acid, linoleic acid. Free ARA modulates the function of ion channels, several receptors and enzymes, via activation as well as inhibition. That explains its fundamental role in the proper function of the brain and muscles and its protective potential against Schistosoma mansoni and S. haematobium infection and tumor initiation, development, and metastasis. Arachidonic acid in cell membranes undergoes reacylation/deacylation cycles, which keep the concentration of free ARA in cells at a very low level and limit ARA availability to oxidation. Metabolites derived from ARA oxidation do not initiate but contribute to inflammation and most importantly lead to the generation of mediators responsible for resolving inflammation and wound healing. Endocannabinoids are oxidation-independent ARA derivatives, critically important for brain reward signaling, motivational processes, emotion, stress responses, pain, and energy balance. Free ARA and metabolites promote and modulate type 2 immune responses, which are critically important in resistance to parasites and allergens insult, directly via action on eosinophils, basophils, and mast cells and indirectly by binding to specific receptors on innate lymphoid cells. In conclusion, the present review advocates the innumerable ARA roles and considerable importance for normal health.

Uric acid is synthesized mainly in the liver, intestines and the vascular endothelium as the end product of an exogenous pool of purines, and endogenously from damaged, dying and dead cells, whereby nucleic acids, adenine and guanine, are degraded into uric acid. Mentioning uric acid generates dread because it is the established etiological agent of the severe, acute and chronic inflammatory arthritis, gout and is implicated in the initiation and progress of the metabolic syndrome. Yet, uric acid is the predominant anti-oxidant molecule in plasma and is necessary and sufficient for induction of type 2 immune responses. These properties may explain its protective potential in neurological and infectious diseases, mainly schistosomiasis. The pivotal protective potential of uric acid against blood-borne pathogens and neurological and autoimmune diseases is yet to be established.

The dramatic rise in cancer incidence, alongside treatment deficiencies, has elevated cancer to the second-leading cause of death globally. The increasing morbidity and mortality of this disease can be traced back to a number of causes, including treatment-related side effects, drug resistance, inadequate curative treatment and tumor relapse. Recently, anti-cancer bioactive peptides (ACPs) have emerged as a potential therapeutic choice within the pharmaceutical arsenal due to their high penetration, specificity and fewer side effects. In this contribution, we present a general overview of the literature concerning the conformational structures, modes of action and membrane interaction mechanisms of ACPs, as well as provide recent examples of their successful employment as targeting ligands in cancer treatment. The use of ACPs as a diagnostic tool is summarized, and their advantages in these applications are highlighted. This review expounds on the main approaches for peptide synthesis along with their reconstruction and modification needed to enhance their therapeutic effect. Computational approaches that could predict therapeutic efficacy and suggest ACP candidates for experimental studies are discussed. Future research prospects in this rapidly expanding area are also offered.

Cell surface biochemical changes, notably excessive increase in outer leaflet sphingomyelin (SM) content, are important in cancer initiation, growth, and immune evasion. Innumerable reports describe methods to initiate, promote, or enhance immunotherapy of clinically detected cancer, notwithstanding the challenges, if not impossibility, of identification of tumor-specific, or associated antigens, the lack of tumor cell surface membrane expression of major histocompatibility complex (MHC) class I alpha and β2 microglobulin chains, and lack of expression or accessibility of Fas and other natural killer cell immune checkpoint molecules. Conversely, SM synthesis and hydrolysis are increasingly implicated in initiation of carcinogenesis and promotion of metastasis. Surface membrane SM readily forms inter- and intra- molecular hydrogen bond network, which excessive tightness would impair cell-cell contact inhibition, inter- and intra-cellular signals, metabolic pathways, and susceptibility to host immune cells and mediators. The present review aims at clarifying the tumor immune escape mechanisms, which face common immunotherapeutic approaches, and attracting attention to an entirely different, neglected, key aspect of tumorigenesis associated with biochemical changes in the cell surface that lead to failure of contact inhibition, an instrumental tumorigenesis mechanism. Additionally, the review aims to provide evidence for surface membrane SM levels and roles in cells resistance to death, failure to respond to growth suppressor signals, and immune escape, and to suggest possible novel approaches to cancer control and cure.

Schistosomiasis is a debilitating disease affecting approximately 600 million people in 74 developing countries, with 800 million, mostly children at risk. To circumvent the threat of having praziquantel (PZQ) as the only drug used for treatment, several PZQ derivatives were synthesized, and drugs destined for other parasites were used with success. A plethora of plant-derived oils and extracts were found to effectively kill juvenile and adult schistosomes, yet none was progressed to pre- and clinical studies except an oleo-gum resin extracted from the stem of Commiphora molmol, myrrh, which action was challenged in several trials. We have proposed an essential fatty acid, a component of our diet and cells, the polyunsaturated fatty acid arachidonic acid (ARA) as a remedy for schistosomiasis, due to its ability to activate the parasite tegument-bound neutral sphingomyelinase, with subsequent hydrolysis of the apical lipid bilayer sphingomyelin molecules, allowing access of specific antibody molecules, and eventual worm attrition. This concept was convincingly supported using larval and adult Schistosoma mansoni and Schistosoma haematobium worms in in vitro experiments, and in vivo studies in inbred mice and outbred hamsters. Even if ARA proves to be an entirely effective and safe therapy for schistosomiasis, it will not prevent reinfection, and accordingly, the need for developing an effective vaccine remains an urgent priority. Our studies have supported the status of S. mansoni calpain, glutathione-S-transferase, aldolase, triose phosphate isomerase, glyceraldehyde 3-phosphate dehydrogenase, enolase, and 2-cys peroxiredoxin as vaccine candidates, as they are larval excreted-secreted products and, contrary to the surface membrane molecules, are entirely accessible to the host immune system effector elements. We have proposed that the use of these molecules, in conjunction with Th2 cytokines-inducing adjuvants for recruiting and activating eosinophils and basophils, will likely lead to development and implementation of a sterilizing vaccine in a near future.