Do Micronutrient and Omega-3 Fatty Acid Supplements Affect Human Maternal Immunity during Pregnancy? A Scoping Review

Maternal dietary micronutrients and omega-3 fatty acids support development of the fetal and neonatal immune system. Whether supplementation is similarly beneficial for the mother during gestation has received limited attention. A scoping review of human trials was conducted looking for evidence of biochemical, genomic, and clinical effects of supplementation on the maternal immune system. The authors explored the literature on PubMed, Cochrane Library, and Web of Science databases from 2010 to the present day using PRISMA-ScR methodology. Full-length human trials in English were searched for using general terms and vitamin A, B12, C, D, and E; choline; iodine; iron; selenium; zinc; and docosahexaenoic/eicosapentaenoic acid. Of 1391 unique articles, 36 were eligible for inclusion. Diverse biochemical and epigenomic effects of supplementation were identified that may influence innate and adaptive immunity. Possible clinical benefits were encountered in malaria, HIV infections, anemia, Type 1 diabetes mellitus, and preventing preterm delivery. Only limited publications were identified that directly explored maternal immunity in pregnancy and the effects of micronutrients. None provided a holistic perspective. It is concluded that supplementation may influence biochemical aspects of the maternal immune response and some clinical outcomes, but the evidence from this review is not sufficient to justify changes to current guidelines.

Spices

The term “spices” has been derived from the word “species,” which was connected to the group of exotic foods in medieval times. Spices and herbs have a long history of culinary use, medicinal properties, and as additives and thus have a distinct place in Ayurveda. Exhibiting the merits of spices by scientific methods still remains a challenge. This review investigates the anti-diabetic properties in preventing and managing diabetics and associated complications with commonly used spices. The bioactive compounds in these spices are additionally discussed. The major aim and object of the present work is to investigate the customary therapeutic usage of basic Indian spices and to corelate their observed pharmacological activities with the presence of explicit bioactive compounds present for the treatment or counteractive action of diabetes. This includes the basic underlying mechanism of their blood glucose lowering property including exploratory experimental evidence from proposed animal and human trials.

Small Molecules Targeting the Disordered Transactivation Domain of the Androgen Receptor Induce the Formation of Collapsed Helical States

Castration-resistant prostate cancer (CRPC) is a lethal condition suffered by ~35% of prostate cancer patients who become resistant to existing FDA-approved drugs. Small molecules that target the intrinsically disordered N-terminal domain of the androgen receptor (AR-NTD) have shown promise in circumventing CPRC drug-resistance. A prodrug of one such compound, EPI-002, entered human trials in 2015 but was discontinued after phase I due to poor potency. The compound EPI-7170 was subsequently found to have improved potency, and a related compound entered human trials in 2020. NMR measurements have localized the strongest effects of these compounds to a transiently helical region of the disordered AR-NTD but no detailed structural or mechanistic rationale exists to explain their affinity to this region or the comparative potency of EPI-7170. Here, we utilize all-atom molecular dynamics simulations to elucidate the binding mechanisms of the small molecules EPI-002 and EPI-7170 to the disordered AR-NTD. We observe that both compounds induce the formation of collapsed helical states in the Tau-5 transactivation domain and that these bound states consist of heterogenous ensembles of interconverting binding modes. We find that EPI-7170 has a higher affinity to Tau-5 than EPI-002 and that the EPI-7170 bound ensemble contains a substantially higher population of collapsed helical states than the bound ensemble of EPI-002. We identify a network of interactions in the EPI-7170 bound ensemble that stabilize collapsed helical conformations. Our results provide atomically detailed binding mechanisms for EPI compounds consistent with NMR experiments that will prove useful for drug discovery for CRPC.

Evaluation of Neuroprotective And Immunomodulatory Properties of Mesenchymal Stem Cells in An Ex-vivo Retinal Explant Model

Background: Mesenchymal stem cells (MSCs) have raised considerable hope for the treatment of glaucoma. Their neuroprotective and regenerative potentials are particularly interesting for this degenerative neuropathy in which retinal ganglion cell (RGC) death leads to a progressive loss of visual field and eventually vision. Yet, despite promising results in animal models, no definitive treatment has been developed, and safety concerns have been reported in human trials. Microglial immunomodulation represents a promising therapeutic approach in which MSCs might play a crucial role. In the present study, we investigated the neuroprotective and immunomodulatory properties as well as the safety of MSCs in an ex vivo neuroretina explant model.Methods: Labeled rat bone marrow MSCs were placed in co-culture with rat retinal explants after optic nerve axotomy. We analyzed the neuroprotective effect of MSCs on RGC survival by immunofluorescence using RBPMS, Brn3a and NeuN markers. Gliosis and retinal microglial activation were measured using GFAP, CD68 and ITGAM mRNA quantification and GFAP, CD68 and Iba1 immunofluorescence staining. We also analyzed the mRNA expression of both ‘M1’ or classically activated state inflammatory cytokines (TNFα, IL1β and IL6), and ‘M2’ or alternatively activated state microglial markers (Arginase 1, IL10, CD163, and TNFAIP6).Results: The number of RGCs was significantly higher in retinal explants cocultured with MSCs compared to the control group at Day 7 following optic nerve axotomy. Retinal explants co-cultured with MSCs showed decreased mRNA markers of gliosis and microglial activation, and immunostaining revealed that GFAP, Iba1 and CD68 were limited to the internal layers of the retina compared to controls showing expression of activated microglia throughout the retina. In addition, MSCs inhibited the M1 phenotype of the microglia. However, edema of the explants was observed in the MSC co-culture group, with an increase of fibronectin labelling at the surface of the explant corresponding to an epiretinal membrane-like phenotype. Conclusion: Using an ex vivo model, we demonstrated a neuroprotective and immunomodulatory effect of MSCs on RGCs. Unfortunately, the presence of MSCs also led to explant edema and epiretinal membrane formation, as described in human trials. Using the MSC secretome might offer the beneficial effects of MSCs without their potential adverse effects, through paracrine signaling.

A Narrative Review: In-vitro Methods for Assessing Bio-Accessibility/Bioavailability of Iron in Plant-Based Foods

In-vitro measurement has the advantage of rapid and convenient method of screening the iron bioavailability within the range of plant-based foods. It is important to do preliminary screening as it provides information which will be useful to identify promising plant sources of iron before moving to human trials. A review on in-vitro methods of bio-accessibility and bioavailability of iron in plant-based foods including fruits, vegetables, cereals and legumes is entailed here. The review will focus on in-vitro methods of iron bioavailability in plant-based foods and the effects of inhibitors and processing on the iron bioavailability. The variation of the methods and updates on a recent INFOGEST method used to measure the bioavailability of iron in plant-based foods will also be discussed.

Rationalizing the design of a broad coverage Shigella vaccine based on evaluation of immunological cross-reactivity among S. flexneri serotypes

No vaccine to protect against an estimated 238,000 shigellosis deaths per year is widely available. S. sonnei is the most prevalent Shigella, and multiple serotypes of S. flexneri, which change regionally and globally, also cause significant disease. The leading Shigella vaccine strategies are based on the delivery of serotype specific O-antigens. A strategy to minimize the complexity of a broadly-protective Shigella vaccine is to combine components from S. sonnei with S. flexneri serotypes that induce antibodies with maximum cross-reactivity between different serotypes. We used the GMMA-technology to immunize animal models and generate antisera against 14 S. flexneri subtypes from 8 different serotypes that were tested for binding to and bactericidal activity against a panel of 11 S. flexneri bacteria lines. Some immunogens induced broadly cross-reactive antibodies that interacted with most of the S. flexneri in the panel, while others induced antibodies with narrower specificity. Most cross-reactivity could not be assigned to modifications of the O-antigen, by glucose, acetate or phosphoethanolamine, common to several of the S. flexneri serotypes. This allowed us to revisit the current dogma of cross-reactivity among S. flexneri serotypes suggesting that a broadly protective vaccine is feasible with limited number of appropriately selected components. Thus, we rationally designed a 4-component vaccine selecting GMMA from S. sonnei and S. flexneri 1b, 2a and 3a. The resulting formulation was broadly cross-reactive in mice and rabbits, inducing antibodies that killed all S. flexneri serotypes tested. This study provides the framework for a broadly-protective Shigella vaccine which needs to be verified in human trials.