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Angewandte Chemie (International Ed. in... Sep 2022H O -driven enzymes are of great interest for industrial biotransformations. Herein, we show for the first time that oxalate oxidase (OXO) is an efficient in situ source...
H O -driven enzymes are of great interest for industrial biotransformations. Herein, we show for the first time that oxalate oxidase (OXO) is an efficient in situ source of H O for one of these biocatalysts, which is known as unspecific peroxygenase (UPO). OXO is reasonably robust, produces only CO as a by-product and uses oxalate as a cheap sacrificial electron donor. UPO has significant potential as an industrial catalyst for selective C-H oxyfunctionalisations, as we confirm herein by testing a diverse drug panel using miniaturised high-throughput assays and mass spectrometry. 33 out of 64 drugs were converted in 5 μL-scale reactions by the UPO with OXO (conversion >70 % for 11 drugs). Furthermore, oxidation of the drug tolmetin was achieved on a 50 mg scale (TON 25 664) with 84 % yield, which was further improved via enzyme immobilization. This one-pot approach ensures adequate H O levels, enabling rapid access to industrially relevant molecules that are difficult to obtain by other routes.
Topics: Carbon Dioxide; Mixed Function Oxygenases; Oxalates; Oxidoreductases; Tolmetin
PubMed: 35916874
DOI: 10.1002/anie.202207831 -
Biomedicines Apr 2023Glioblastoma (GBM) is the most prevalent and aggressive adult brain tumor. Despite multi-modal therapies, GBM recurs, and patients have poor survival (~14 months)....
Glioblastoma (GBM) is the most prevalent and aggressive adult brain tumor. Despite multi-modal therapies, GBM recurs, and patients have poor survival (~14 months). Resistance to therapy may originate from a subpopulation of tumor cells identified as glioma-stem cells (GSC), and new treatments are urgently needed to target these. The biology underpinning GBM recurrence was investigated using whole transcriptome profiling of patient-matched initial and recurrent GBM (recGBM). Differential expression analysis identified 147 significant probes. In total, 24 genes were validated using expression data from four public cohorts and the literature. Functional analyses revealed that transcriptional changes to recGBM were dominated by angiogenesis and immune-related processes. The role of MHC class II proteins in antigen presentation and the differentiation, proliferation, and infiltration of immune cells was enriched. These results suggest recGBM would benefit from immunotherapies. The altered gene signature was further analyzed in a connectivity mapping analysis with QUADrATiC software to identify FDA-approved repurposing drugs. Top-ranking target compounds that may be effective against GSC and GBM recurrence were rosiglitazone, nizatidine, pantoprazole, and tolmetin. Our translational bioinformatics pipeline provides an approach to identify target compounds for repurposing that may add clinical benefit in addition to standard therapies against resistant cancers such as GBM.
PubMed: 37189838
DOI: 10.3390/biomedicines11041219 -
Frontiers in Chemistry 2018The goal of this study is to provide tools to minimize in the development of novel lipid-based nanotherapeutics, in favor of a rational design process. For this...
The goal of this study is to provide tools to minimize in the development of novel lipid-based nanotherapeutics, in favor of a rational design process. For this purpose, we present case-study examples of biophysical assays that help addressing issues of lipid-based nanotherapeutics' profiling and assist in the design of lipid nanocarriers for therapeutic usage. The assays presented are rooted in spectroscopic methods (steady-state and time-resolved fluorescence; UV-Vis derivative spectroscopy; fluorescence anisotropy and fluorescence lifetime image microscopy) and allow accessing physical-chemical interactions between drugs and lipid nanocarriers, as well as studying interactions between lipid-based nanotherapeutics and membranes and/or proteins, as this is a key factor in predicting their therapeutic and effects. Derivative spectroscopy revealed Naproxen's high distribution (Log ≈ 3) in different lipid-based nanocarriers (micelles and unilamellar or multilamellar vesicles) confirming the adequacy of such systems for encapsulating this anti-inflammatory drug. Fluorescence quenching studies revealed that the anti-inflammatory drugs Acemetacin and Indomethacin can reach an inner location at the lipid nanocarrier while being anchored with its carboxylic moiety at the polar headgroup. The least observed quenching effect suggested that Tolmetin is probably located at the polar headgroup region of the lipid nanocarriers and this superficial location may translate in a fast drug release from the nanocarriers. Fluorescent anisotropy measurements indicated that the drugs deeply buried within the lipid nanocarrier where the ones that had a greater fluidizing effect which can also translate in a faster drug release. The drug binding strength to serum albumin was also compared for a free drug (Clonixin) or for the same drug after encapsulation in a lipid nanocarrier DSPC:DODAP (2:1). Under both conditions there is a strong binding to serum albumin, at one binding site, suggesting the need to produce a stealth nanosystem. Finally the cellular uptake of lipid nanocarriers loaded with Daunorubicin was investigated in cancer cells using fluorescence lifetime imaging microscopy. From the images obtained it was possible to conclude that even at short incubation times (15 min) there was a distribution of the drug in the cytoplasm, whereas for longer incubation periods (4 h) the drug has reached the nucleus.
PubMed: 30109226
DOI: 10.3389/fchem.2018.00323 -
World Journal of Clinical Cases Apr 2024Various non-steroidal anti-inflammatory drugs (NSAIDs) have been used for juvenile idiopathic arthritis (JIA). However, the optimal method for JIA has not yet been...
BACKGROUND
Various non-steroidal anti-inflammatory drugs (NSAIDs) have been used for juvenile idiopathic arthritis (JIA). However, the optimal method for JIA has not yet been developed.
AIM
To perform a systematic review and network meta-analysis to determine the optimal instructions.
METHODS
We searched for randomized controlled trials (RCTs) from PubMed, EMBASE, Google Scholar, CNKI, and Wanfang without restriction for publication date or language at August, 2023. Any RCTs that comparing the effectiveness of NSAIDs with each other or placebo for JIA were included in this network meta-analysis. The surface under the cumulative ranking curve (SUCRA) analysis was used to rank the treatments. value less than 0.05 was identified as statistically significant.
RESULTS
We included 8 RCTs (1127 patients) comparing 8 different instructions including meloxicam (0.125 qd and 0.250 qd), Celecoxib (3 mg/kg bid and 6 mg/kg bid), piroxicam, Naproxen (5.0 mg/kg/d, 7.5 mg/kg/d and 12.5 mg/kg/d), inuprofen (30-40 mg/kg/d), Aspirin (60-80 mg/kg/d, 75 mg/kg/d, and 55 mg/kg/d), Tolmetin (15 mg/kg/d), Rofecoxib, and placebo. There were no significant differences between any two NSAIDs regarding ACR Pedi 30 response. The SUCRA shows that celecoxib (6 mg/kg bid) ranked first (SUCRA, 88.9%), rofecoxib ranked second (SUCRA, 68.1%), Celecoxib (3 mg/kg bid) ranked third (SUCRA, 51.0%). There were no significant differences between any two NSAIDs regarding adverse events. The SUCRA shows that placebo ranked first (SUCRA, 88.2%), piroxicam ranked second (SUCRA, 60.5%), rofecoxib (0.6 mg/kg qd) ranked third (SUCRA, 56.1%), meloxicam (0.125 mg/kg qd) ranked fourth (SUCRA, 56.1%), and rofecoxib (0.3 mg/kg qd) ranked fifth (SUCRA, 56.1%).
CONCLUSION
In summary, celecoxib (6 mg/kg bid) was found to be the most effective NSAID for treating JIA. Rofecoxib, piroxicam, and meloxicam may be safer options, but further research is needed to confirm these findings in larger trials with higher quality studies.
PubMed: 38680254
DOI: 10.12998/wjcc.v12.i12.2056 -
Iranian Journal of Pharmaceutical... 2017
PubMed: 28979298
DOI: No ID Found -
The Journal of Physical Chemistry. C,... May 2024An aqueous colloidal suspension of gold nanoparticles (AuNPs) may be condensed into a thin fractal film at the polarizable liquid-liquid interface formed between two...
An aqueous colloidal suspension of gold nanoparticles (AuNPs) may be condensed into a thin fractal film at the polarizable liquid-liquid interface formed between two immiscible electrolyte solutions upon injection of millimolar concentrations of sodium chloride to the aqueous phase. By adjusting the interfacial polarization conditions (negative, intermediate, and positive open-circuit potentials), the morphology of the film is modified, resulting in unique surface plasmon properties of the film, which enable in situ surface-enhanced Raman spectroscopy (SERS). Intense SERS signals are observed at the polarizable liquid-liquid interface when micromolar concentrations of tolmetin, a nonsteroidal anti-inflammatory drug, are entrapped in the AuNP fractal film. The change in the signal intensity, averaged over multiple spectra, with respect to the concentration of tolmetin, depends on the polarization conditions and suggests the presence of chemical-induced damping effects on the surface plasmons of the gold film.
PubMed: 38774155
DOI: 10.1021/acs.jpcc.4c00937