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Proteins and peptides (PPs) have gradually become more attractive therapeutic molecules than small molecular drugs due to their high selectivity and efficacy, but fewer side effects. Owing to the poor stability and limited permeability through gastrointestinal (GI) tract and epithelia, the therapeutic PPs are usually administered by parenteral route. Given the big demand for oral administration in clinical use, a variety of researches focused on developing new technologies to overcome GI barriers of PPs, such as enteric coating, enzyme inhibitors, permeation enhancers, nanoparticles, as well as intestinal microdevices. Some new technologies have been developed under clinical trials and even on the market. This review summarizes the history, the physiological barriers and the overcoming approaches, current clinical and preclinical technologies, and future prospects of oral delivery of PPs., Graphical abstract The current strategies for improving oral absorption of proteins and peptides (PPs) include stabilization, absorption enhancement and mucus-related technologies. Most of marketed oral PP products employ two or more strategies.Image 1

Erythrocytes (red blood cells, RBCs) are the most abundant circulating cells in the blood and have been widely used in drug delivery systems (DDS) because of their features of biocompatibility, biodegradability, and long circulating half-life. Accordingly, a “camouflage” comprised of erythrocyte membranes renders nanoparticles as a platform that combines the advantages of native erythrocyte membranes with those of nanomaterials. Following injection into the blood of animal models, the coated nanoparticles imitate RBCs and interact with the surroundings to achieve long-term circulation. In this review, the biomimetic platform of erythrocyte membrane-coated nano-cores is described with regard to various aspects, with particular focus placed on the coating mechanism, preparation methods, verification methods, and the latest anti-tumor applications. Finally, further functional modifications of the erythrocyte membranes and attempts to fuse the surface properties of multiple cell membranes are discussed, providing a foundation to stimulate extensive research into multifunctional nano-biomimetic systems., Graphical abstract In this review, the biomimetic platform of erythrocyte membrane-coated nano-cores is described with regard to coating mechanism, preparation methods, verification methods, and the latest anti-tumor applications. Finally, further functional modifications of the erythrocyte membranes and attempts to fuse the surface properties of multiple cell membranes are discussed.fx1

Many diseases are now associated with aberrant epigenetics and gene expression changes. Epigenetics can be modified by factors like diet. One dietary factor, folic acid, is consumed in various forms including supplements, energy drinks, and fortified grains. It was hypothesized high levels of folic acid would affect gene expression and enzyme activity of chromatin modifying enzymes as well as dendritic spine densities in a commonly utilized neuron model, the SHSY5Y cell. Decreased MBD2 and MECP2 were discovered upon treatment of SHSY5Y cells with a 2x folic acid dose. Corresponding decreases in dendritic spines were apparent in the 2x folic acid treated cells as well. Activity of DNMTs and H3K4 HMTs was altered. Further, H3K4me1, H3K4me3, H3K9Ac, and global DNA methylation were decreased in the 2x folic acid treated cells. Further studies are warranted to determine if the effects of excess folic acid are detrimental to organismal physiology., Highlights • The 2x folic acid treatment in SHSY5Y cells induces a significant decrease in MBD2 and MECP2 mRNA expression. • The excess folic acid also causes a significant increase in dendritic spines in SHSY5Y cells. • The 2x folic acid treatment increases DNMT activity and significantly decreases H3K4 HMT activity in SHSY5Y cells. • These findings align with some of those seen in autism spectrum disorders.

Non-coding small RNA molecules, the microRNAs (miRNAs), contribute decisively to the epigenetic regulation processes in cancer cells. Problematic pathogenic properties of cancer cells and the response of cancers towards anticancer drugs are highly influenced by miRNAs. Both increased drug activity and formation of tumor resistance are regulated by miRNAs. Further to this, the survival and proliferation of cancer cells and the formation of metastases is based on the modulated expression of certain miRNAs. In particular, drug-resistant cancer stem-like cells (CSCs) depend on the presence and absence of specific miRNAs. Fortunately, several small molecule natural compounds were discovered that target miRNAs involved in the modulation of tumor aggressiveness and drug resistance. This review gives an overview of the effects of a selection of naturally occurring small molecules (alkaloids, organosulfur compounds, aliphatic carboxylic acids and water-soluble vitamins) on miRNAs that are closely tangled with cancer diseases. Keywords: MiRNA, Alkaloids, Organosulfur compounds, Aliphatic carboxylic acids, Water-soluble vitamins, Anticancer drugs

The effect of folic acid (FA) on breast cancer (BC) risk is uncertain. We hypothesised that this uncertainty may be due, in part, to differential effects of FA between BC cells with different phenotypes. To test this we investigated the effect of treatment with FA concentrations within the range of unmetabolised FA reported in humans on the expression of the transcriptome of non-transformed (MCF10A) and cancerous (MCF7 and Hs578T) BC cells. The total number of transcripts altered was: MCF10A, seventy-five (seventy up-regulated); MCF7, twenty-four (fourteen up-regulated); and Hs578T, 328 (156 up-regulated). Only the cancer-associated geneTAGLNwas altered by FA in all three cell lines. In MCF10A and Hs578T cells, FA treatment decreased pathways associated with apoptosis, cell death and senescence, but increased those associated with cell proliferation. The folate transporters SLC19A1, SLC46A1 and FOLR1 were differentially expressed between cell lines tested. However, the level of expression was not altered by FA treatment. These findings suggest that physiological concentrations of FA can induce cell type-specific changes in gene regulation in a manner that is consistent with proliferative phenotype. This has implications for understanding the role of FA in BC risk. In addition, these findings support the suggestion that differences in gene expression induced by FA may involve differential activities of folate transporters. Together these findings indicate the need for further studies of the effect of FA on BC.