Increased Cerebrospinal Fluid Adenosine 5'-Triphosphate Levels in Patients with Guillain-Barré Syndrome and Chronic Inflammatory Demyelinating Polyneuropathy.

Background: Extracellular adenosine 5'-triphosphate (ATP) acts as a signaling molecule in the peripheral nerves, regulating myelination after nerve injury. The present study examined whether the cerebrospinal fluid (CSF) ATP levels in patients with Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP) are related to disease severity. Methods: CSF ATP levels in 13 patients with GBS and 18 patients with CIDP were compared with those in a control group of 16 patients with other neurological diseases (ONDs). In patients with CIDP, CSF ATP levels were compared before and after treatment. The correlations between CSF ATP levels and other factors, including clinical data and CSF protein levels, were also evaluated. Results: Median CSF ATP levels were significantly higher in patients with GBS and CIDP than in those with ONDs. When patients with CIDP were classified into two groups depending on their responsiveness to immunotherapy, median CSF ATP levels were significantly higher in good responders than in ONDs. CSF ATP levels tended to decrease after treatment in patients with CIDP. In patients with CIDP, there is a negative correlation between CSF ATP and CSF protein levels. Conclusions: CSF ATP levels were increased in patients with GBS and CIDP. In particular, CSF ATP levels tended to decrease following treatment in patients with CIDP. CSF ATP levels may be useful biomarkers for the diagnosis or monitoring of therapeutic effects in patients with GBS and CIDP.

Catechol-O-methyltransferase and monoamine oxidase B inhibitory activities of Australian bee pollen.

Bee pollen is an apicultural product collected by honeybees from flower stamens and used as a functional food worldwide. In the present study, we aim to elucidate the functions of Australian bee pollen. Australian bee pollen extracts and their main components were tested for catechol-O-methyltransferase (COMT) and monoamine oxidase B (MAOB) inhibitory activities. These enzymes are key neurotransmitters involved in Parkinson's disease and depression. Myricetin (5), tricetin (6), and luteolin (7) exhibited high COMT inhibitory activities (half maximal inhibitory concentration [IC50] = 23.3, 13.8, and 47.4 µM, respectively). In contrast, 5, 7, and annulatin (8) exhibited MAOB inhibitory activities (IC50 = 89.7, 32.8, and 153 µM, respectively). Quantitative analysis via high-performance liquid chromatography revealed that 5 was abundant in Australian bee pollen extracts. Our findings suggest that 5 contributes to the COMT and MAOB inhibitory activities of Australian bee pollen.

Lung Cancer Wherein Durvalumab Induced Both Anti-CRMP-5 Antibody-related Paraneoplastic Neurological Syndromes and Neurological Adverse Events.

A 68-year-old man with small-cell lung cancer developed anti-collapsin response-mediator protein (CRMP)-5 antibody-related paraneoplastic neurological syndrome (PNS) presenting with ataxia and chorea during treatment with durvalumab. As a result of steroid therapy, anti-CRMP-5 antibodies became negative, hyperintense lesions on brain magnetic resonance imaging disappeared, and neurological symptoms improved. After resuming durvalumab, he became unable to walk due to neurological adverse events (nAEs). There have been no reported cases manifesting PNSs and nAEs as a result of the same immune checkpoint inhibitors (ICIs) administered at different times. Resuming ICIs in patients diagnosed with PNSs should be performed with prudence.

The protective effects of blueberry honey from Canada against H2O2-induced cytotoxicity in human buccal mucosal cells.

OBJECTIVES: Several clinical trials have been conducted worldwide to evaluate the efficacy of honey against stomatitis. However, it is unclear which types of honey are effective at preventing and/or treating stomatitis. This study aimed to evaluate the potencies of several types of honey in preventing and/or curing aphthous stomatitis in in vitro studies. METHODS: The following experiments were performed: H2O2-induced cytotoxicity and mucosal cell migration in a scratch assay using buccal mucosa squamous carcinoma (HO-1-N-1) cells and the cellular expression of heme oxygenase-1 (HO-1) mRNA encoding an enzyme involved in protection against oxidative stress by real-time RT-PCR analysis, and liquid-liquid extraction and UHPLC analysis in order to examine the active components of honey. RESULTS: Of the 13 types of honey used, Canadian blueberry honey exhibited the protective effect on H2O2-induced cytotoxicity and enhanced cell migration. In addition, blueberry honey increased the expression of HO-1 mRNA with and without cotreatment with H2O2. With regard to active components of blueberry honey, the water-soluble components with a mass of >10 kDa showed a cytoprotective effect, but they have not been identified. CONCLUSION: Canadian blueberry honey, but not the other types of honey, prevents H2O2-induced oxidation of cells, probably through activation of the antioxidant and cytoprotective enzyme HO-1. Blueberry honey also enhanced cell migration, which may be relevant to wound healing. The results of this study suggest the possibility of prophylactic and therapeutic effects of Canadian blueberry honey on human stomatitis that could complement existing treatments.

NMR and HPLC profiling of bee pollen products from different countries.

Bee pollen, a beehive product collected from flowers by honeybees, contains over 250 biological substances, and has attracted increasing attention as a functional food. However, commercial bee pollen products are often multifloral, and samples from different countries vary significantly. There is no universal standard for objective quality assessment of bee pollen based on its chemical composition. Here, we report metabolomic analysis of 11 bee pollen samples from Spain, China, and Australia for quality control. The characteristics of the samples depend on the sucrose, nucleoside, amino acid, and flavanol concentrations. Bee pollen samples from Spain and Australia had higher sucrose and adenosine concentrations, whereas those from China had higher trigonelline, uridine, and cytidine concentrations. Interestingly, acetic acid was only detected in samples from China. These components can be used to identify the country of origin. The obtained profiles of the samples will contribute to universal standard development for bee pollen products.

Chemical constituents of Brazilian Propolis from the state of Bahia and their growth inhibitory activities against cancer cells.

A novel 2-phenoxychromone (1) and five known flavones (2-6) were isolated from northeastern Brazilian propolis in the state of Bahia. The chemical structures of these six compounds were determined by spectroscopic investigations and single-crystal X-ray analysis. The isolated compounds showed growth-inhibitory activities, in varying degrees, against human tumor cell lines. This is the first report on the discovery of a novel 2-phenoxychromone from propolis.

Discovery of a Novel Diterpene in Brown Propolis from the State of Parana, Brazil.

Propolis is a resinous substance collected by honeybees from certain plant sources. The components of propolis depend on the vegetation of the area in which apiculture is practiced. In Brazil, there are several types of propolis including 'green,' 'red' and 'brown'. Brazilian brown propolis from the state of Parana characteristically includes diterpenes, and we discovered a novel clerodane diterpene, rel-(5S,6S,8R,9R,10S,18R,19S)-18,19-epoxy-2-oxocleroda-3,12(E),14- triene-6,18,19-triol 18,19-diacetate 6-benzoate (3) and five known diterpenes (1, 2, 4, 5 and 6). The chemical structure of the novel diterpene 3 was determined using 1D- and 2D-NMR spectroscopic analyses. Furthermore, the activities of the isolated diterpenes on growth inhibition of several human cancer cell lines (LNCaP, MCF-7, DLD-1 and A549) were evaluated in vitro; diterpene 3 exhibited a potent inhibition of cell growth, and its activity was approximately 15 times higher than that of the other diterpenes.

Cassane-type diterpenoids from Caesalpinia echinata (Leguminosae) and their NF-κB signaling inhibition activities.

Fourteen cassane-type diterpenoids, echinalides H-U, were isolated from the stem of Caesalpinia echinata Lam. (Leguminosae). The structures of the echinalides were elucidated by spectroscopic investigation, including 2D NMR spectroscopic analysis. The structures of echinalide H and echinalide T were further confirmed by single-crystal X-ray diffraction. The absolute configurations of echinalides H, I, J and K were determined by CD spectroscopy. Additionally, the absolute configurations of echinalide L and M were determined by chemical conversion from echinalide H. These compounds were evaluated for inhibitory activity against nuclear factor κB (NF-κB). Echinalide M showed the most potent inhibitory activity (47±11% at 5µM) toward NF-κB-responsive gene expression.

New cassane-type diterpenoids of Caesalpinia echinata (Leguminosae) exhibiting NF-κB inhibitory activities.

Seven new cassane-type diterpenoids, echinalides A-G (1-7), were isolated from the stem of Caesalpinia echinata LAM. (Leguminosae). The structures were established on the basis of their chemical properties and spectroscopic evidence, including two dimensional (2D)-NMR analysis. These compounds were assessed for inhibitory activity against nuclear factor κB (NF-κB). Echinalides C and D, in particular, significantly inhibited NF-κB-responsive reporter gene expression at 5.0 µM, an effect almost equivalent to that of parthenolide, a known potent inhibitor of NF-κB.

Culcitiolides E-J, six new eremophilane-type sesquiterpene derivatives from Senecio culcitioides.

Culcitiolides E-J (1-6), six new eremophilane-type sesquiterpenes, were isolated from the stem of Senecio culcitioides SCH. BIP. (Asteraceae). The structures were determined by detailed NMR spectral analysis. The inhibitory activities of these compounds against nuclear factor κB (NF-κB)-dependent gene expression were assessed. Culcitiolides E, H, and I potently inhibited NF-κB-induced gene expression at 20 µM.

Design and synthesis of photolabile caged cytokinin.

Cytokinins are phytohormones that regulate diverse developmental processes throughout the life of a plant. trans-Zeatin, kinetin, benzyladenine and dihydrozeatin are adenine-type cytokinins that are perceived by the AHK cytokinin receptors. Endogenous cytokinin levels are critical for regulating plant development. To manipulate intracellular cytokinin levels, caged cytokinins were designed on the basis of the crystal structure of the AHK4 cytokinin receptor. The caged cytokinin was photolyzed to release the cytokinin molecule inside the cells and induce cytokinin-responsive gene expression. The uncaging of intracellular caged cytokinins demonstrated that cytokinin-induced root growth inhibition can be manipulated with photo-irradiation. This caged cytokinin system could be a powerful tool for cytokinin biology.

Culcitiolides A-D, four new eremophilane-type sesquiterpene derivatives from Senecio culcitioides.

Four new eremophilane-type sesquiterpenes, culcitiolides A-D, were isolated from the stem of Senecio culcitioides Sch. Bip (Asteraceae). Their structures were established by detailed 2D NMR spectroscopic and single-crystal X-ray experiments. These compounds were assessed for inhibitory activity against nuclear factor kappaB (NF-kappaB). Culcitiolides C and D at 20 microM showed 97 and 100% inhibition of NF-kappaB activity, respectively.