The effects of CO2 in the storage atmosphere on color, firmness, ascorbic acid (AA), anthocyanins, flavonoids, phenolics, total antioxidant activity, and antiproliferative activity of strawberry fruit have been investigated. “Northeaster” and “Earliglow” strawberries were stored in air or in 20% CO2 (in air) at 3 °C for 20 d. Color changes in Northeaster were delayed more by CO2 treatment than in Earliglow. Firmness of CO2‐stored fruit increased slightly compared with those stored in air. The increases in total and reduced AA concentrations during air storage were usually prevented by CO2 storage in both cultivars. Dehydroascorbic acid (DHA) concentrations increased during CO2 storage. Anthocyanins and flavonoids, and total antioxidant activity of both cultivars were higher in air‐stored fruit than in CO2‐stored fruit. The total phenolic concentration was lower in CO2‐stored Earliglow fruit than in air, but storage treatment did not affect that of Northeaster. A 40 mg/mL concentration of Northeaster strawberry extract inhibited about 80% of HepG2 human liver cancer cell proliferation. CO2 treatment did not affect the antiproliferative activity of strawberry fruits, but antiproliferative activity was greater at harvest than after storage.
9,9′‐Spirobifluorene‐based closo‐o‐carboranyl (SFC1 and SFC2) compounds and their nido‐derivatives (nido‐SFC1 and nido‐SFC2) were prepared and characterized. The two closo‐compounds displayed major absorption bands assignable to π–π* transitions involving the spirobifluorene group, as well as weak intramolecular charge‐transfer (ICT) transitions between the o‐carboranes and their spirobifluorene moieties. The nido‐compounds exhibited slightly blueshifted absorption bands resulting from the absence of the ICT transitions corresponding to the o‐carborane moieties due to the anionic character of the nido‐o‐carboranes. While SFC1 exhibited only high‐energy emissions in THF at 298 K (only from locally excited (LE) states assignable to π–π* transitions on the spirobifluorene group), remarkable emissions in the low‐energy region were observed in the rigid state such as in THF at 77 K and in the film state. SFC2 displayed intense emissions in the low‐energy region in all states. The fact that neither of the nido‐derivatives of SFC1 and SFC2 exhibited low‐energy emissions and the TD‐DFT calculation results of each closo‐compound clearly verified that the low‐energy emission was based on ICT‐based radiative decay. The conformational barriers from each relative energy calculation upon changing the dihedral angles around the o‐carborane cages for both compounds confirmed that the rotation of the o‐carborane cages and terminal phenyl rings for SFC1 is freer than that for SFC2.
This study determined the effects of blueberry fermentation by Lactobacillus plantarum on antioxidant and anticancer activities. The fermented blueberries extracted with 80% ethanol (FBE) showed increased superoxide dismutase‐like activity, increased scavenging of DPPH and alkyl radicals, and increased antiproliferative activity against human cervical carcinoma HeLa cells by inducing apoptosis. Seven representative phenolic compounds (malvidin 3‐O‐glucopyranoside, gallic acid, protocatechuic acid, catechol, chlorogenic acid, syringic acid, and epigallocatechin) in FBE were measured by high‐performance liquid chromatography at different fermentation times. The content of each phenolic compound in the FBE was dependent on the fermentation period. Protocatechuic acid and catechol levels increased significantly with fermentation time. Of these three major compounds (protocatechuic acid, catechol, and chlorogenic acid), catechol showed the most significant anticancer activity when HeLa cells were treated with each of these three compounds alone or mixed in various ratios. Pearson's product‐moment correlation analysis revealed that the increases in antioxidant and anticancer activities following blueberry fermentation were positively correlated with the phenolic acids present in FBE. Practical Application Blueberries fermented with a tannase‐producing lactic acid bacteria (LAB), Lactobacillus plantarum showed higher antioxidant activities and antiproliferative activities against human cervical carcinoma HeLa cells than did raw blueberries. L. plantarum fermentation biotransformed blueberry polyphenols into active phenol metabolites with strong antioxidant and antiproliferative activities. Our results suggest that fermented blueberries are rich in phenolic acids, which are a promising source of natural antioxidants and anticancer drugs and can be used as additives in food, pharmaceuticals, and cosmetic preparations.
Ligands selectively targeting beta-amyloid in the living brain are promising candidates of therapeutics and early diagnosis tools for Alzheimer's disease. Among the major stages of beta-amyloid aggregation, monomers and oligomers are excellent targets to reduce neurotoxic brain damages for prevention of the disease progression, while oligomers and fibrils, abundant in the late stage of the disease, are pathological objectives to develop reliable imaging probes. So far, there have been many efforts to develop a wide variety of monovalent beta-amyloid ligands such as thioflavin T, PIB, FDDNP, curcumin, and tramiprosate. However, pathology of Alzheimer's disease is not fully understood yet so that there is currently no cure and further investigations on Alzheimer's disease are needed. For past several years, multivalent beta-amyloid ligands have offered an alternative route by enhancing binding affinity of drug candidates. In addition, it has been revealed that not only neurotoxicity due to the protein misfolding but also other factors are involved in the beta-amyloid cascade such as oxidative stress, inflammation, metal chelation, and several types of neurotransmitters. Thus, there have been numerous studies to improve binding affinities of single beta-amyloid ligands via adopting multivalent effects or to develop drug candidates targeting multiple stages of the pathological cascade. In this review, multivalent and multifunctional beta-amyloid ligands and their promising aspects as an alternative approach to Alzheimer's disease are discussed.
Despite recent groundbreaking advances in multiple myeloma (MM) treatment, most MM patients ultimately experience relapse, and the relapse biology is not entirely understood. To define altered gene expression in MM relapse, gene expression profiles were examined and compared among 16 MM patients grouped by 12 months progression-free survival (PFS) after autologous stem cell transplantation. To maximize the difference between prognostic groups, patients at each end of the PFS spectrum (the four with the shortest PFS and four with the longest PFS) were chosen for additional analyses. We discovered that integrin-α8 (ITGA8) is highly expressed in MM patients with early relapse. The integrin family is well known to be involved in MM progression; however, the role of integrin-α8 is largely unknown. We functionally overexpressed integrin-α8 in MM cell lines, and surprisingly, stemness features including HIF1α, VEGF, OCT4, and Nanog, as well as epithelial mesenchymal transition (EMT)-related phenotypes, including N-cadherin, Slug, Snail and CXCR4, were induced. These, consequently, enhanced migration and invasion abilities, which are crucial to MM pathogenesis. Moreover, the gain of integrin-α8 expression mediated drug resistance against melphalan and bortezomib, which are the main therapeutic agents in MM. The cBioPortal genomic database revealed that ITGA8 have significant tendency to co-occur with PDGFRA and PDGFRB and their mRNA expression were up-regulated in ITGA8 overexpressed MM cells. In summary, integrin-α8, which was up-regulated in MM of early relapse, mediates EMT-like phenotype, enhancing migration and invasion; therefore, it could serve as a potential marker of MM relapse and be a new therapeutic target.
Thermolytic formation of transient 1,1-bis(trimethylsilyl)-2-dimethylamino-2-trimethylsiloxysilene (2) from N,N-dimethyl(tris(trimethylsilyl)silyl)methaneamide (1) in presence of a series of alcohols was investigated. The products are, however, not the expected alcohol-silene addition adducts but silylethers formed in nearly quantitative yields. Thermolysis of 1 in the presence of both alcohols (MeOH or iPrOH) and 1,3-dienes (1,3-butadiene or 2,3-dimethyl-1,3-butadiene) gives alkyl-tris(trimethylsilyl)silylethers and the [4+2] cycloadducts between the silene and diene, which confirms the presence of 2 and that it is unreactive towards alcohols. The observed silylethers are substitution adducts where the amide group of the silylamide is replaced by an alkoxy group, and the reaction time is reflected in the steric bulk of the alcohol. Indeed, the formation of silylethers from the reaction of alcohols with silylamide represents a new base-free method for protection of alcohols. The protection reactions using 1 progresses at elevated temperatures, or alternatively, under acid catalysis at ambient temperature, and similar protections can be carried out with N-cyclohexyl(triphenylsilyl)methaneamide and N,N-dimethyl(trimethylsilyl)methaneamide. The latter silylamide can be used under neutral conditions at room temperature. The only by-products are formamides (N,N-dimethylformamide (DMF) or N-cyclohexylformamide), and the reactions can be performed without solvent. In addition to alcohols we also examined the method for protection of diols, thiols and carboxylic acids, and also these reactions proceeded in high yields and with good selectivities.
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