Essential Oil of Brachylaena hutchinsii Hutch from Tanzania: Antimicrobial Activity and Composition

East and Central African Journal of Pharmaceutical Sciences Vol.6(3) 2003: 61-6

PARP inhibition utilized in combination therapy with Olaparib-Temozolomide to achieve disease stabilization in a rare case of BRCA1-mutant, metastatic myxopapillary ependymoma.

Myxopapillary ependymoma (MPE) is a primary tumor of the central nervous system (CNS), characteristically an indolent malignancy involving the spinal conus medullaris, Filum terminale or cauda equina. We present a rare case of MPE, recurrent in the pelvic soft tissue with eventual pleural and intra-pulmonary metastasis. Refractory to repeated gross resection, adjuvant radiotherapy, platinum-based chemotherapy and temozolomide exploitation of mutant somatic BRCA1 status with the addition of a poly (ADP-ribose); polymerase inhibitor (PARPi) in a novel combination regimen with olaparib-temozolomide (OT) has achieved stable radiological disease after 10 cycles

Mechanism of enzymatic degradation of the azo dye Orange II determined by ex situ 1H nuclear magnetic resonance and electrospray ionization-ion trap mass spectrometry

Removal of azo dye effluents generated by textile photography industries is a main issue in wastewater treatment. Enzymatic treatment of dyes appears to be one of the most efficient processes for their degradation. The elucidation of degradation pathways is of special interest considering health and environmental priorities. Ex situ nuclear magnetic resonance (NMR) spectroscopy and electrospray ionization (ESI)-ion trap mass spectrometry performed directly on incubation medium have been used for the first time to follow kinetics of sulfonated azo dye Orange II enzymatic degradation. Nine transformation products were identified using these complementary analyses performed ex situ without any prior treatment. Three types of cleavage are proposed for the degradation pathway: (i) a symmetrical splitting of the azo linkage that leads to the formation of 4-aminobenzenesulfonate (and 1-amino-2-naphthol, not detected); (ii) an asymmetrical cleavage on the naphthalene side that generates 1,2-naphthoquinone and 4-diazoniumbenzenesulfonate as products, with the latter one being transformed into 4-hydroxybenzensulfonate; and (iii) a third degradation pathway that leads to 2-naphthol and 4-hydroxybenzenesulfonate. Moreover, three other intermediates have been identified. This study, which constitutes the first concomitant use of 1H NMR spectroscopy and ESI-ion trap mass spectrometry in this field, illustrates the indubitable interest of the ex situ approac

Adult brain tumour research in 2024: Status, challenges and recommendations

In 2015, a groundswell of brain tumour patient, carer and charity activism compelled the UK Minister for Life Sciences to form a brain tumour research task and finish group. This resulted, in 2018, with the UK government pledging £20m of funding, to be paralleled with £25m from Cancer Research UK, specifically for neuro-oncology research over the subsequent 5 years. Herein, we review if and how the adult brain tumour research landscape in the United Kingdom has changed over that time and what challenges and bottlenecks remain. We have identified seven universal brain tumour research priorities and three cross-cutting themes, which span the research spectrum from bench to bedside and back again. We discuss the status, challenges and recommendations for each one, specific to the United Kingdom

Charged-Higgs phenomenology in the Aligned two-Higgs-doublet model

The alignment in flavour space of the Yukawa matrices of a general two-Higgs-doublet model results in the absence of tree-level flavour-changing neutral currents. In addition to the usual fermion masses and mixings, the aligned Yukawa structure only contains three complex parameters, which are potential new sources of CP violation. For particular values of these three parameters all known specific implementations of the model based on discrete Z_2 symmetries are recovered. One of the most distinctive features of the two-Higgs-doublet model is the presence of a charged scalar. In this work, we discuss its main phenomenological consequences in flavour-changing processes at low energies and derive the corresponding constraints on the parameters of the aligned two-Higgs-doublet model.Comment: 46 pages, 19 figures. Version accepted for publication in JHEP. References added. Discussion slightly extended. Conclusions unchange

Research highlights from the 2018 European Respiratory Society International Congress: airway disease.

The annual European Respiratory Society (ERS) International Congress (held in Paris in 2018) was once again a platform for discussion of the highest-quality scientific research, cutting-edge techniques and innovative new therapies within the respiratory field. This article discusses only some of the high-quality research studies presented at this year's Congress, with a particular focus on airway diseases including asthma, chronic obstructive pulmonary disease (COPD), bronchiectasis and cough, as presented through Assembly 5 of the ERS (Airway Diseases: Asthma and COPD). The authors establish the key take-home messages of these studies, compare their findings and place them in the context of current understanding

Incompressible Fluids of the de Sitter Horizon and Beyond

There are (at least) two surfaces of particular interest in eternal de Sitter space. One is the timelike hypersurface constituting the lab wall of a static patch observer and the other is the future boundary of global de Sitter space. We study both linear and non-linear deformations of four-dimensional de Sitter space which obey the Einstein equation. Our deformations leave the induced conformal metric and trace of the extrinsic curvature unchanged for a fixed hypersurface. This hypersurface is either timelike within the static patch or spacelike in the future diamond. We require the deformations to be regular at the future horizon of the static patch observer. For linearized perturbations in the future diamond, this corresponds to imposing incoming flux solely from the future horizon of a single static patch observer. When the slices are arbitrarily close to the cosmological horizon, the finite deformations are characterized by solutions to the incompressible Navier-Stokes equation for both spacelike and timelike hypersurfaces. We then study, at the level of linearized gravity, the change in the discrete dispersion relation as we push the timelike hypersurface toward the worldline of the static patch. Finally, we study the spectrum of linearized solutions as the spacelike slices are pushed to future infinity and relate our calculations to analogous ones in the context of massless topological black holes in AdS$_4$.Comment: 27 pages, 8 figure

CD69 is a TGF-β/1α,25-dihydroxyvitamin D3 target gene in monocytes

CD69 is a transmembrane lectin that can be expressed on most hematopoietic cells. In monocytes, it has been functionally linked to the 5-lipoxygenase pathway in which the leukotrienes, a class of highly potent inflammatory mediators, are produced. However, regarding CD69 gene expression and its regulatory mechanisms in monocytes, only scarce data are available. Here, we report that CD69 mRNA expression, analogous to that of 5-lipoxygenase, is induced by the physiologic stimuli transforming growth factor-β (TGF-β) and 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3) in monocytic cells. Comparison with T- and B-cell lines showed that the effect was specific for monocytes. CD69 expression levels were increased in a concentration-dependent manner, and kinetic analysis revealed a rapid onset of mRNA expression, indicating that CD69 is a primary TGF-β/1α,25(OH)2D3 target gene. PCR analysis of different regions of the CD69 mRNA revealed that de novo transcription was initiated and proximal and distal parts were induced concomitantly. In common with 5-lipoxygenase, no activation of 0.7 kb or ~2.3 kb promoter fragments by TGF-β and 1α,25(OH)2D3 could be observed in transient reporter assays for CD69. Analysis of mRNA stability using a transcription inhibitor and a 3′UTR reporter construct showed that TGF-β and 1α,25(OH)2D3 do not influence CD69 mRNA stability. Functional knockdown of Smad3 clearly demonstrated that upregulation of CD69 mRNA, in contrast to 5-LO, depends on Smad3. Comparative studies with different inhibitors for mitogen activated protein kinases (MAPKs) revealed that MAPK signalling is involved in CD69 gene regulation, whereas 5-lipoxygenase gene expression was only partly affected. Mechanistically, we found evidence that CD69 gene upregulation depends on TAK1-mediated p38 activation. In summary, our data indicate that CD69 gene expression, conforming with 5-lipoxygenase, is regulated monocyte-specifically by the physiologic stimuli TGF-β and 1α,25(OH)2D3 on mRNA level, although different mechanisms account for the upregulation of each gene

Two distinct populations of Bovine IL-17+ T-cells can be induced and WC1+IL-17+γδ T-cells are effective killers of protozoan parasites

IL-17 has emerged as a key player in the immune system, exhibiting roles in protection from infectious diseases and promoting inflammation in autoimmunity. Initially thought to be CD4 T-cell-derived, the sources of IL-17 are now known to be varied and belong to both the innate and adaptive arms of the immune system. Mechanisms for inducing IL-17 production in lymphoid cells are thought to rely on appropriate antigenic stimulation in the context of TGF-β1, IL-6 and/or IL-1β. Using culture protocols adapted from human studies, we have effectively induced both bovine CD4+ and WC1+ γδ T-cells to produce IL-17 termed Th17 and γδ17 cells, respectively. The negative regulatory effect of IFN-γ on mouse and human IL-17 production can be extended to the bovine model, as addition of IFN-γ decreases IL-17 production in both cell types. Furthermore we show that infection with the protozoan Neospora caninum will induce fibroblasts to secrete pro-IL-17 factors thereby inducing a γδ17 phenotype that preferentially kills infected target cells. Our study identifies two T-cell sources of IL-17, and is the first to demonstrate a protective effect of IL-17+ T-cells in ruminants. Our findings offer further opportunities for future adjuvants or vaccines which could benefit from inducing these responses