[Modified Premedication of Infusion Reaction with Obinutuzumab Therapy].

Obinutuzumab frequently triggers an infusion reaction(IR). In the GALLIUM study, despite the use of corticosteroids, antipyretic analgesics, and antihistamines to prevent IR, IR occurred at a high frequency of 68.2% for all Grades and 12.4% for Grades 3 or higher. The dose of methylprednisolone was increased from 80 mg administered in the GALLIUM study to 125 mg, and the development of IR was investigated in 30 patients with follicular lymphoma who received the initial dose of obinutuzumab. The incidence of IR was 43.3% for all Grades and 0% for Grades 3 or higher, and no serious IR was observed. It also had no effect on infectious diseases. Increased doses of corticosteroids were well tolerated and suggested as an effective method for reducing the frequency of IR.

Allylic hydroxylation of triterpenoids by a plant cytochrome P450 triggers key chemical transformations that produce a variety of bitter compounds.

Cucurbitacins are highly oxygenated triterpenoids characteristic of plants in the family Cucurbitaceae and responsible for the bitter taste of these plants. Fruits of bitter melon (Momordica charantia) contain various cucurbitacins possessing an unusual ether bridge between C5 and C19, not observed in other Cucurbitaceae members. Using a combination of next-generation sequencing and RNA-Seq analysis and gene-to-gene co-expression analysis with the ConfeitoGUIplus software, we identified three P450 genes, CYP81AQ19, CYP88L7, and CYP88L8, expected to be involved in cucurbitacin biosynthesis. CYP81AQ19 co-expression with cucurbitadienol synthase in yeast resulted in the production of cucurbita-5,24-diene-3ß,23α-diol. A mild acid treatment of this compound resulted in an isomerization of the C23-OH group to C25-OH with the concomitant migration of a double bond, suggesting that a nonenzymatic transformation may account for the observed C25-OH in the majority of cucurbitacins found in plants. The functional expression of CYP88L7 resulted in the production of hydroxylated C19 as well as C5-C19 ether-bridged products. A plausible mechanism for the formation of the C5-C19 ether bridge involves C7 and C19 hydroxylations, indicating a multifunctional nature of this P450. On the other hand, functional CYP88L8 expression gave a single product, a triterpene diol, indicating a monofunctional P450 catalyzing the C7 hydroxylation. Our findings of the roles of several plant P450s in cucurbitacin biosynthesis reveal that an allylic hydroxylation is a key enzymatic transformation that triggers subsequent processes to produce structurally diverse products.

Identification of triterpene biosynthetic genes from Momordica charantia using RNA-seq analysis.

Cucurbitaceae plants contain characteristic triterpenoids. Momordica charantia, known as a bitter melon, contains cucurbitacins and multiflorane type triterpenes, which confer bitter tasting and exhibit pharmacological activities. Their carbon skeletons are biosynthesized from 2,3-oxidosqualene by responsible oxidosqualene cyclase (OSC). In order to identify OSCs in M. charantia, RNA-seq analysis was carried out from ten different tissues. The functional analysis of the resulting four OSC genes revealed that they were cucurbitadienol synthase (McCBS), isomultiflorenol synthase (McIMS), ß-amyrin synthase (McBAS) and cycloartenol synthase (McCAS), respectively. Their distinct expression patterns based on RPKM values and quantitative RT-PCR suggested how the characteristic triterpenoids were biosynthesized in each tissue. Although cucurbitacins were finally accumulated in fruits, McCBS showed highest expression in leaves indicating that the early step of cucurbitacins biosynthesis takes place in leaves, but not in fruits. Abbreviations: OSC: oxidosqualene cyclase; RPKM: reads perkilobase of exon per million mapped reads.

Dexamethasone Downregulates Endothelin Receptors and Reduces Endothelin-Induced Production of Matrix Metalloproteinases in Cultured Rat Astrocytes.

In brain disorders, astrocytes change phenotype to reactive astrocytes and are involved in the induction of neuroinflammation and brain edema. The administration of glucocorticoids (GCs), such as dexamethasone (Dex), reduces astrocytic activation, but the mechanisms underlying this inhibitory action are not well understood. Endothelins (ETs) promote astrocytic activation. Therefore, the effects of Dex on ET receptor expressions were examined in cultured rat astrocytes. Treatment with 300 nM Dex for 6-48 hours reduced the mRNA expression of astrocytic ETA and ETB receptors to 30-40% of nontreated cells. Levels of ETA and ETB receptor proteins became about 50% of nontreated cells after Dex treatment. Astrocytic ETA and ETB receptor mRNAs were decreased by 300 nM hydrocortisone. The effects of Dex and hydrocortisone on astrocytic ET receptors were abolished in the presence of mifepristone, a GC receptor antagonist. Although Dex did not decrease the basal levels of matrix metalloproteinase (MMP) 3 and MMP9 mRNAs, pretreatment with Dex reduced ET-induced increases in MMP mRNAs. The effects of ET-1 on the release of MMP3 and MMP9 proteins were attenuated by pretreatment with Dex. ET-1 stimulated the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) in cultured astrocytes. Pretreatment with Dex reduced the ET-induced increases in ERK1/2 phosphorylation. In contrast, pretreatment with Dex did not affect MMP production or ERK1/2 phosphorylation induced by phorbol myristate acetate, a protein kinase C activator. These results indicate that Dex downregulates astrocytic ET receptors and reduces ET-induced MMP production.

Properties of Plasmon-Induced Photoelectric Conversion on a TiO2/NiO p-n Junction with Au Nanoparticles.

We have successfully fabricated all-solid-state plasmonic photoelectric conversion devices composed of titanium dioxide (TiO2)/nickel oxide (NiO) p-n junctions with gold nanoparticles (Au-NPs) as prototype devices for a plasmonic solar cell. The characteristics of the crystal structures and the photoelectric properties of the all-solid-state devices were demonstrated. We observed that the crystalline structure of the NiO thin film and the interfacial structure of TiO2/Au-NPs/NiO changed significantly during an annealing treatment. Furthermore, the photoelectric conversion devices exhibited plasmon-induced photocurrent generation in the visible-wavelength region. The photocurrent may result from plasmon-induced charge separation. The photoelectric conversion properties via plasmon-induced charge separation were strongly correlated with the morphology of the TiO2/Au-NPs/NiO interface. The long-term stability of the plasmonic photoelectric conversion device was found to be very high because a stable photocurrent was observed even after irradiation for 3 days.

Photoelectrochemical Behavior of Self-Assembled Ag/Co Plasmonic Nanostructures Capped with TiO2.

The use of localized surface plasmon resonance induced by Ag nanostructures is a promising way for high-efficiency photoelectric conversion. In plasmonic photoelectric conversion devices, however, the chemical instability of Ag in ambient atmosphere and its immediate deterioration have been a critical issue. Here, we propose a Ag-Co nanostructure array embedded in a TiO2 matrix as a plasmonic resonator that ensures long-term stability. We also developed an electrochemical process to remove surface Co nanoclusters protecting fresh Ag from exposure to air. This enabled us to "unseal" Ag at the desired time. Furthermore, we confirmed photoelectric conversion using Ag-Co-TiO2 nanocomposite films in contact with solution; the photoelectric conversion was substantially enhanced by the plasmon resonance of the Ag nanorods. The Ag nanostructures sealed in a TiO2 matrix are expected to be used in other application fields, such as catalytisis and sensing, in which a fresh Ag surface is needed.

Near-Infrared Plasmon-Assisted Water Oxidation.

We report the stoichiometric evolution of oxygen via water oxidation by irradiating a plasmon-enhanced photocurrent generation system with near-infrared light (λ: 1000 nm), in which gold nanostructures were arrayed on the surface of TiO2 electrode. It is considered that multiple electron holes generated by plasmon-induced charge excitation led to the effective recovery of water oxidation after the electron transfer from gold to TiO2. The proposed system containing a gold nanostructured TiO2 electrode may be a promising artificial photosynthetic system using near-infrared light.