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Human noroviruses are the most common pathogens known to cause acute gastroenteritis, a condition that can lead to severe illness among immunocompromised individuals such as organ transplant recipients and the elderly. To date, no safe and effective vaccines or therapeutic agents have been approved for treating norovirus infections. Therefore, we aimed to demonstrate the virucidal activity of grape seed extract (GSE), which contains >83% proanthocyanidins, against murine norovirus (MNV), a surrogate for human norovirus. GSE showed virucidal activity against MNV in a dose- and time-dependent manner. Atomic force microscopic analysis showed viral particle aggregates after treatment of MNV with GSE. MNV treated with 50 µg/mL of GSE for 10 min resulted in the absence of pathogenicity in an animal model of infection, indicating that GSE has irreversible virucidal activity against MNV particles. Thus, GSE may aid in the development of treatments for norovirus infections.

Theranostics (bifunction of therapeutics and diagnostics) has attracted increasing attention due to its efficiency that can reduce the physical and financial burden on patients. One of the promising materials for theranostics is calcium phosphate (CP) and it is biocompatible and can be functionalized not only with drug molecules but also with rare earth ions to show photoluminescence that is necessary for the diagnostic purpose. Such the CP-based hybrids are formed in vivo by interacting between functional groups of organic molecules and inorganic ions. It is of great importance to elucidate the interaction of CP with the photofunctional species and the drug molecules to clarify the relationship between the existing state and function. Well-designed photofunctional CPs will contribute to biomedical fields as highly-functional ormultifunctional theranostic materials at the nanoscales. In this review, we describe the hybridization between CPs and heterogeneous species, mainly focusing on europium(III) ion and methylene blue molecule as the representative photofunctional species for theranostics applications.

The effect of hydrogen bonds around the active site of Anabaena [2Fe-2S] ferredoxin (Fd) on a vertical ionization potential of the reduced state (IP(red)) is examined based on the density functional theory (DFT) calculations. The results indicate that a single hydrogen bond increases the relative stability of the reduced state, and shifts IP(red) to a reductive side by 0.31–0.33 eV, regardless of the attached sulfur atoms. In addition, the IP(red) value can be changed by the number of hydrogen bonds around the active site. The results also suggest that the redox potential of [2Fe-2S] Fd is controlled by the number of hydrogen bonds because IP(red) is considered to be a major factor in the redox potential. Furthermore, there is a possibility that the redox potentials of artificial iron-sulfur clusters can be finely controlled by the number of the hydrogen bonds attached to the sulfur atoms of the cluster.

Skeletal muscle atrophy is the decrease in muscle mass and strength caused by reduced protein synthesis/accelerated protein degradation. Various conditions, such as denervation, disuse, aging, chronic diseases, heart disease, obstructive lung disease, diabetes, renal failure, AIDS, sepsis, cancer, and steroidal medications, can cause muscle atrophy. Mechanistically, inflammation, oxidative stress, and mitochondrial dysfunction are among the major contributors to muscle atrophy, by modulating signaling pathways that regulate muscle homeostasis. To prevent muscle catabolism and enhance muscle anabolism, several natural and synthetic compounds have been investigated. Recently, polyphenols (i.e., natural phytochemicals) have received extensive attention regarding their effect on muscle atrophy because of their potent antioxidant and anti-inflammatory properties. Numerous in vitro and in vivo studies have reported polyphenols as strongly effective bioactive molecules that attenuate muscle atrophy and enhance muscle health. This review describes polyphenols as promising bioactive molecules that impede muscle atrophy induced by various proatrophic factors. The effects of each class/subclass of polyphenolic compounds regarding protection against the muscle disorders induced by various pathological/physiological factors are summarized in tabular form and discussed. Although considerable variations in antiatrophic potencies and mechanisms were observed among structurally diverse polyphenolic compounds, they are vital factors to be considered in muscle atrophy prevention strategies.

Gluconasturtiin, a glucosinolate present in watercress, is hydrolysed by myrosinase to form gluconasturtiin-isothiocyanate (GNST-ITC), which has potential chemopreventive effects; however, the underlying mechanisms of action have not been explored, mainly in human cell lines. The purpose of the study is to evaluate the cytotoxicity of GNST-ITC and to further assess its potential to induce apoptosis. GNST-ITC inhibited cell proliferation in both human hepatocarcinoma (HepG2) and human breast adenocarcinoma (MCF-7) cells with IC50 values of 7.83 µM and 5.02 µM, respectively. Morphological changes as a result of GNST-ITC-induced apoptosis showed chromatin condensation, nuclear fragmentation, and membrane blebbing. Additionally, Annexin V assay showed proportion of cells in early and late apoptosis upon exposure to GNST-ITC in a time-dependent manner. To delineate the mechanism of apoptosis, cell cycle arrest and expression of caspases were studied. GNST-ITC induced a time-dependent G2/M phase arrest, with reduction of 82% and 93% in HepG2 and MCF-7 cell lines, respectively. The same treatment also led to the subsequent expression of caspase-3/7 and -9 in both cells demonstrating mitochondrial-associated cell death. Collectively, these results reveal that GNST-ITC can inhibit cell proliferation and can induce cell death in HepG2 and MCF-7 cancer cells via apoptosis, highlighting its potential development as an anticancer agent.

Dietary R-sulforaphane is a highly potent inducer of the Keap1/Nrf2/ARE pathway. Furthermore, sulforaphane is currently being used in clinical trials to assess its effects against different tumour processes. This study reports an efficient preparation of enantiopure R-sulforaphane based on the enzymatic hydrolysis of its natural precursor glucoraphanin. As an alternative to broccoli seeds, we have exploited Tuscan black kale seeds as a suitable source for gram-scale production of glucoraphanin. The defatted seed meal contained 5.1% (w/w) of glucoraphanin that was first isolated through an anion exchange chromatographic process, and then purified by gel filtration. The availability of glucoraphanin (purity ≈ 95%, weight basis) has allowed us to develop a novel simple hydrolytic process involving myrosinase (EC 3.2.1.147) in a biphasic system to directly produce R-sulforaphane. In a typical experiment, 1.09 g of enantiopure R-sulforaphane was obtained from 150 g of defatted Tuscan black kale seed meal.

Moringin [4-(α-L-rhamnosyloxy) benzyl isothiocyanate] is an isothiocyanate extracted from Moringa oleifera seeds. It is an antioxidant known for several biological properties useful in the treatment of neurodegenerative diseases. Several neurodegenerative disorders such as Parkinson’s and Alzheimer’s diseases are linked to dysfunctional mitochondria due to the resulting increase of Reactive Oxygen Species (ROS). Stem cell-based therapeutic treatments in neurodegenerative diseases provide an alternative strategy aimed to replace the impaired tissue. In this study were investigated the deregulated genes involved in mitophagy in the human periodontal ligament stem cells pretreated with moringin. The RNA-seq study reveals the downregulation of PINK1, with a fold change (FC) of −0.56, such as the genes involved in the phagophore formation (MAP1LC3B FC: −0.73, GABARAP FC: −0.52, GABARAPL1 FC: −0.70, GABARAPL2 FC: −0.39). The moringin pretreatment downregulates the pro−apoptotic gene BAX (−0.66) and upregulates the anti-apoptotic genes BCL2L12 (FC: 1.35) and MCL1 (FC: 0.36). The downregulation of the most of the caspases (CASP1 FC: −1.43, CASP4 FC: −0.18, CASP6 FC: −1.34, CASP7 FC: −0.46, CASP8 FC: −0.65) implies the inactivation of the apoptotic process. Our results suggest that mitochondrial dysfunctions induced by oxidative stress can be inhibited by moringin pretreatment in human periodontal ligament stem cells (hPDLSCs).

The electron conductivity of an extended metal atom chain (EMAC) that consisted of penta-nickel(II) ions bridged by oligo-α-pyridylamino ligands was examined by density functional theory (DFT) and elastic scattering Green’s functions (ESGF) calculations. The calculated results revealed that an intramolecular ferromagnetic (FM) coupling state showed a higher conductivity in comparison with an anti-ferromagnetic (AFM) coupling state. The present results suggest the potential of the complex as a molecular switch as well as a molecular wire.

Colorectal cancer is the third most commonly occurring cancer in men and the second most commonly occurring cancer in women worldwide. We have recently reported that curcuminoid complexes labelled with gallium-68 have demonstrated preferential uptake in HT29 colorectal cancer and K562 lymphoma cell lines compared to normal human lymphocytes. In the present study, we report a new gallium-68-labelled curcumin derivative (68Ga-DOTA-C21) and its initial validation as marker for early detection of colorectal cancer. The precursor and non-radioactive complexes were synthesized and deeply characterized by analytical methods then the curcuminoid was radiolabelled with gallium-68. The in vitro stability, cell uptake, internalization and efflux properties of the probe were studied in HT29 cells, and the in vivo targeting ability and biodistribution were investigated in mice bearing HT29 subcutaneous tumour model. 68Ga-DOTA-C21 exhibits decent stability (57 ± 3% after 120 min of incubation) in physiological media and a curcumin-mediated cellular accumulation in colorectal cancer cell line (121 ± 4 KBq of radiotracer per mg of protein within 60 min of incubation). In HT29 tumour-bearing mice, the tumour uptake of 68Ga-DOTA-C21 is 3.57 ± 0.3% of the injected dose per gram of tissue after 90 min post injection with a tumour to muscle ratio of 2.2 ± 0.2. High amount of activity (12.73 ± 1.9% ID/g) is recorded in blood and significant uptake of the radiotracer occurs in the intestine (13.56 ± 3.3% ID/g), lungs (8.42 ± 0.8% ID/g), liver (5.81 ± 0.5% ID/g) and heart (4.70 ± 0.4% ID/g). Further studies are needed to understand the mechanism of accumulation and clearance; however, 68Ga-DOTA-C21 provides a productive base-structure to develop further radiotracers for imaging of colorectal cancer.

Glucosinolates (GLs) are natural compounds present in species of the order Brassicales and precursors of bioactive isothiocyanates (ITCs). In the recent years, they have been studied mainly for their chemopreventive as well as novel chemotherapeutics properties. Among them 4-(α-L-rhamnosyloxy)benzyl glucosinolate (glucomoringin; GMG), purified from seeds of Moringa oleifera Lam., a plant belonging to the Moringaceae family, represents an uncommon member of the GL family with peculiar characteristics. This short communication reports new evidences about the properties of GMG and presents a new innovative utilization of the molecule. The bioactivation of GMG by myrosinase enzyme just before treatment, permits to maximize the power of the final product of the reaction, which is the 4-(α-L-rhamnosyloxy)benzyl isothiocyanate (GMG-ITC). We tested the antibiotic activity of this latter compound on two strains of pathogens affecting the health of patients in hospital, namely Staphylococcus aureus and Enterococcus casseliflavus, and on the yeast Candida albicans. Results show that the sensibility of S. aureus BAA-977 strain and E. casseliflavus to GMG-ITC treatment reveals an important possible application of this molecule in the clinical care of patients, more and more often resistant to traditional therapies.

Glucoraphasatin (GRH), a glucosinolate present abundantly in the plants of the Brassicaceae family, is hydrolyzed by myrosinase to raphasatin, which is considered responsible for its cancer chemopreventive activity; however, the underlying mechanisms of action have not been investigated, particularly in human cell lines. The aims of this study are to determine the cytotoxicity of raphasatin, and to evaluate its potential to cause apoptosis and modulate cell cycle arrest in human breast adenocarcinoma MCF-7 cells. The cytotoxicity was determined following incubation of the cells with glucoraphasatin or raphasatin (0⁻100 µM), for 24, 48, and 72 h. GRH displayed no cytotoxicity as exemplified by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. When myrosinase was added to the incubation system to convert GRH to raphasatin, cytotoxicity was evident. Exposure of the cells to raphasatin stimulated apoptosis, as was exemplified by cell shrinkage, membrane blebbing, chromatin condensation, and nuclear fragmentation. Moreover, using Annexin V-FITC assay, raphasatin induced apoptosis, as witnessed by changes in cellular distribution of cells, at different stages of apoptosis; in addition, raphasatin caused the arrest of the MCF-7 cells at the G2 + M phase. In conclusion, raphasatin demonstrated cancer chemopreventive potential against human breast adenocarcinoma (MCF-7) cells, through induction of apoptosis and cell cycle arrest.

Antimicrobial resistance is one of the major clinical concerns, making the discovery of new antimicrobial drugs desirable. Moringin (MOR), the major isothiocyanate produced from Moringa oleifera seeds, could represent an alternative therapeutic strategy to commonly used antibiotics. The aim of our study was to investigate the antimicrobial effect of MOR conjugated with α-cyclodextrin (MOR/α-CD), a complex with an improved solubility and stability in aqueous solutions. Our data demonstrated that MOR/α-CD was able to exert antimicrobial activity against the S. aureus reference strains (ATCC 25923, ATCC 6538, and ATCC BAA-977). Moreover, MOR/α-CD showed bacteriostatic effects (MIC = minimum inhibitory concentration = 0.5 mg/mL) and bactericidal properties (MBC = minimum bactericidal concentration = 1 mg/mL) against the overall assessed strains. In addition, MOR/α-CD showed bactericidal activity against the S. aureus strain ATCC BAA-977 after treatment with erythromycin (Ery), which induced clindamycin-resistance on the erm (A) gene. This evidence led us to assume that MOR/α-CD could be a promising antimicrobial agent against strains with the clindamycin-resistant phenotype (CC-resistant).

Moringin, obtained via enzymatic conversion of the glucosinolate precursor glucomoringin, is an uncommon member of the isothiocyanate class, and has been proven to possess a broad range of biological activities such as antitumor activity, protection against neurodegenerative disorders and bactericidal effects. Since moringin is weakly soluble in water and unstable in aqueous medium, cyclodextrins (CDs) were considered for the development of a new moringin formulation, with a view to improving its solubility and stability in aqueous solution for use as an anti-inflammatory. A combined structural study using proton nuclear magnetic resonance (1H-NMR), diffusion-ordered spectroscopy (DOSY) and ion mobility mass spectrometry (IM-MS) is reported, highlighting the formation of a 1:1 α-CD/moringin inclusion complex. The association constant K was determined (1300 M−1 at 300 K). Completion of the structural characterization was performed by T-ROESY and MS/MS experiments, which evidenced the mode of penetration of moringin into α-CD. Finally, the “chaperone-like” properties of α-CD with respect to the stability of moringin have been highlighted.

The fac-Ir(ppy)3 complex, where ppy denotes 2-phenylpyridine, is one of the well-known luminescent metal complexes having a high quantum yield. However, there have been no specific molecular design guidelines for color tuning. For example, it is still unclear how its optical properties are changed when changing substitution groups of ligands. Therefore, in this study, differences in the electronic structures and optical properties among several substituted fac-Ir(ppy)3 derivatives are examined in detail by density functional theory (DFT) and time-dependent DFT (TD-DFT) calculations. On the basis of those results, we present rational design guidelines for absorption and emission color tuning by modifying the species of substituents and their substitution positions.

The use of plant-derived products as antimicrobial agents has been investigated in depth. Isothiocyanates (ITCs) are bioactive products resulting from enzymatic hydrolysis of glucosinolates (GLs), the most abundant secondary metabolites in the botanical order Brassicales. Although the antimicrobial activity of ITCs against foodborne and plant pathogens has been well documented, little is known about their antimicrobial properties against human pathogens. This review collects studies that focus on this topic. Particular focus will be put on ITCs’ antimicrobial properties and their mechanism of action against human pathogens for which the current therapeutic solutions are deficient and therefore of prime importance for public health. Our purpose was the evaluation of the potential use of ITCs to replace or support the common antibiotics. Even though ITCs appear to be effective against the most important human pathogens, including bacteria with resistant phenotypes, the majority of the studies did not show comparable results and thus it is very difficult to compare the antimicrobial activity of the different ITCs. For this reason, a standard method should be used and further studies are needed.

The amounts of selenium (Se), iron (Fe), and zinc (Zn) in the liver, kidney, and spleen as a function of age of rats measured using instrumental neutron activation analysis were compared between Se-deficient (SeD) rats and normal rats. The SeD model rats can live for more than 50 weeks. The effect of Se-deficinecy in rats might be weak, compared to the marked malfunction of GSH-Px. The SeD rats can be considered as a model of nonlethal chronic oxidative stress. Fluctuations of Fe and Zn in the liver of Se-deficient rats were observed. The amount of redox-relating minerals, such as Fe and Zn, in SeD rat organs is changeable depending on the age.