107 research outputs found
Arsonium and phosphonium-functionalized gold nanoparticles for mitochondria targeted therapeutics
This thesis presents a body of original research describing the synthesis, characterisation and biological properties of novel arsonium- and phosphonium- alkylthiosulfate zwitterions and thioacetate salts and gold nanoparticles functionalized with triphenylarsoniumpropylthiolate ligands.
Chapter 1 presents a systematic literature review of the preparation of functionalized gold nanoparticles, their biomedical properties, the biological applications of phosphonium and arsonium ions and phosphonium-functionalized nanomaterials. Details of the analytical methods employed to characterize all the compounds produced in this study are outlined in chapter 2.
Chapter 3 reports the synthesis of the triphenylarsoniopropylthiosulfate zwitterion and ω-
thioacetylpropyl(triphenyl)arsonium bromide salt. Both compounds have been characterized spectroscopically and by single crystal X-ray diffraction. The thiosulfate group
of the triphenylarsoniopropylthiosulfate zwitterion and the thioacetate group of the ω- thioacetylpropyl(triphenyl)arsonium salt undergo reductive cleavage, forming the
corresponding triphenylarsoniumpropylthiolate ions that attach to the surface of gold in a modification of the established Brust-Schiffrin method for preparing gold nanoparticles. TEM studies show the triphenylarsonium-functionalized gold nanoparticles to be spherical
with diameters of c.a. 3nm. The presence of the triphenylarsonium groups has been confirmed by Raman and XPS spectroscopy and mass spectrometry. It also describes the synthesis, characterisation and biological properties of a family of phosphoniopropylthiosulfate zwitterions and ω-thioacetylpropyl(triaryl)phosphonium salts derived from tri(4-methoxyphenyl)phosphine, tri(2,6-dimethoxyphenyl)phosphine and tri(2,4,6-trimethoxyphenyl)phosphine.
The IC50 values of the triphenylarsoniopropylthiosulfate zwitterion, ω-thioacetylpropyl- (triphenyl)arsonium bromide salt, triphenylarsonium-functionalized gold nanoparticles and family of phosphoniopropylthiosulfate zwitterions and ω-
thioacetylpropyl(triaryl)phosphonium salts derived from tri(4-methoxyphenyl)phosphine, tri(2,6-dimethoxyphenyl)phosphine and tri(2,4,6-trimethoxyphenyl)phosphine have been
determined against PC3 prostate cancer cells using MTT and CellTiter-Glo assays and are reported in Chapter 4. The uptake of the triphenylarsonium-functionalized gold
nanoparticles by PC3 and Human Fibroblast cells has also been determined by ICP-OES spectroscopy
Table4_Cuproptosis scoring model predicts overall survival and assists in immunotherapeutic decision making in pancreatic carcinoma.XLSX
Background: Cuproptosis is a newly identified form of non-apoptotic cell death that is associated with the progression and treatment responses in pancreatic adenocarcinoma (PAAD). However, its impact on oncology and tumor microenvironment (TME) remains unclear.Methods: Hub genes were identified using least absolute shrinkage and selection operator (LASSO) Cox regression for 25 newly reported cuproptosis-related regulators and subjected to stepwise regression to obtain cuproptosis-related score (CuRS). Additionally, the clinical significance, functional status, role on TME, and genomic variation of CuRS were further examined systematically.Results: A CuRS model incorporating TRAF2, TRADD, USP21, FAS, MLKL, TNFRSF10B, MAPK8, TRAF5, and RIPK3 was developed. The stability and accuracy of this risk model as an independent prognostic factor for PAAD were confirmed in the training and external validation cohorts. Patients in the high-CuRS group had “cold” tumors with active tumor proliferation and immunosuppression, whereas those in the low-CuRS group comprised “hot” tumors with active immune function and cell killing capacity. Additionally, patients in the high-CuRS group carried fewer genomic copy number variations (CNVs) and greater somatic mutations. Furthermore, patients in the low- and high-CuRS groups exhibited increased sensitivity to immunotherapy and chemotherapy, respectively.Conclusion: We developed and validated a robust CuRS model based on cuproptosis to assess patients’ prognoses and guide clinical decision-making. Overall, the findings of this study are expected to contribute to the comprehensive understanding of cuproptosis and facilitate precise treatment of PAAD.</p
Facile Preparation of Well-Defined Hydrophilic Core–Shell Upconversion Nanoparticles for Selective Cell Membrane Glycan Labeling and Cancer Cell Imaging
Molecular imaging enables in situ
visualization of biomolecules
in living organisms and creates numerous opportunities for basic biological
research and early disease diagnosis. As luminescent probes for molecular
imaging, lanthanide-doped upconversion nanoparticles (UCNPs) exhibit
superior performance compared to conventional fluorescent dyes in
many ways, including high tissue penetration depth and minimized autofluorescence
and photobleaching, making them particularly advantageous for imaging
analysis. Although various synthesis methods have been reported, the
preparation of high quality, water-soluble UCNPs remains challenging.
For in situ imaging, glycans on the cell surface are particularly
attractive due to their key roles in cellular activity and disease
occurrence and development. However, glycan imaging is a challenging
task due to their diverse structures and incompatibility with genetically
encoded fluorescent tagging techniques. Herein, we report a new type
of highly water-soluble, lectin-functionalized core–shell UCNP
synthesized by surface-initiated atom transfer radical polymerization
(SI-ATRP) for selective cell membrane glycan labeling and cancer cell
imaging. SI-ATRP modification results in controlled growth of hydrophilic
polymers on the UCNP surface and well-defined core–shell structure,
producing UCNPs with improved biocompatibility and intact luminance
property. Furthermore, the numerous functional groups on the polymer
brush shell provide a large number of binding sites and 3D support
for lectin immobilization. The increased loading density and diversified
architecture of the immobilized lectins facilitates multivalent binding
between the lectins and the glycans on the cell surface and leads
to selective labeling of highly metastatic hepatocellular carcinoma
cells (HCCHM3) in vitro and successful in vivo imaging of HCCHM3 inoculated
mice
Additional file 1: Figure S1. of RpoN2- and FliA-regulated fliTX is indispensible for flagellar motility and virulence in Xanthomonas oryzae pv. oryzae
Coomassie blue staining of the FliTX protein expressed and extracted from E. coli strain BL21. M: Molecular marker; 1: FliTX in the soluble fraction; 2: purified FliTX; 3: FliTX in the insoluble fraction. (TIFF 424 kb
Additional file 2: Table S1. of RpoN2- and FliA-regulated fliTX is indispensible for flagellar motility and virulence in Xanthomonas oryzae pv. oryzae
The primers used in this study. (DOCX 17 kb
An Improved and Enantioselective Preparation of the Telaprevir Bicyclic [3.3.0] Proline Intermediate and Reuse of Unwanted Enantiomer
An
improved, concise, and efficient preparation of the telaprevir
bicyclic [3.3.0] proline intermediate is presented. The key steps,
control points, and the whole process are optimized. The synthesis
of racemic intermediate was accomplished in five steps in above 56%
overall yield up to 100 g scale with only some simple separations
and treatments in the whole process. The new and crucial chiral resolution
of the proline intermediate was systematically studied, and the target
chiral intermediate was obtained in acceptable yield (30%) and excellent
ee value (>99% ee) by a simple washing. The cost of the target
chiral
intermediate and wastes of the whole process were at least doubly
reduced after the effective reuse of the unwanted chiral amino acid
by successful decarboxylation
Glycosaminoglycanomics of Cultured Cells Using a Rapid and Sensitive LC-MS/MS Approach
Glycosaminoglycans
(GAGs), a family of polysaccharides widely distributed in eukaryotic
cells, are responsible for a wide array of biological functions. Quantitative
disaccharide compositional analysis is one of the primary ways to
characterize the GAG structure. This structural analysis is typically
time-consuming (1–2 weeks) and labor intensive, requiring GAG
recovery and multistep purification, prior to the enzymatic/chemical
digestion of GAGs, and finally their analysis. Moreover, 10<sup>5</sup>–10<sup>7</sup> cells are usually required for compositional
analysis. We report a sensitive, rapid, and quantitative analysis
of GAGs present in a small number of cells. Commonly studied cell
lines were selected based on phenotypic properties related to the
biological functions of GAGs. These cells were lysed using a commercial
surfactant reagent, sonicated, and digested with polysaccharide lyases.
The resulting disaccharides were recovered by centrifugal filtration,
labeled with 2-aminoacridone, and analyzed by liquid chromatography
(LC)-mass spectrometry (MS). Using a highly sensitive MS method, multiple
reaction monitoring (MRM), the limit of detection for each disaccharide
was reduced to 0.5–1.0 pg, as compared with 1.0–5.0
ng obtained using standard LC-MS analysis. Sample preparation time
was reduced to 1–2 days, and the cell number required was reduced
to 5000 cells for complete GAG characterization to as few
as 500 cells for the characterization of the major GAG disaccharide
components. Our survey of the glycosaminoglycanomes of the 20 selected
cell lines reveals major differences in their GAG amounts and compositions.
Structure–function relationships are explored using these data,
suggesting the utility of this method in cellular glycobiology
The experiment schedules of immunization, infection and blood collection.
<p>White, long arrows represent that the groups were treated with UVAC immunization. Black, long arrows represent that the groups were infected with normal cercariae (<i>n</i> = 7).</p
<i>P</i> values obtained from the statistical analysis of the effects of the treatment and time in the experiment.
<p><i>P</i> values obtained from the statistical analysis of the effects of the treatment and time in the experiment.</p
Comparison of IgG1/IgG2 ratio in the acute infection with <i>Schistosoma japonicum</i> among the three groups.
<p>Comparison of IgG1/IgG2 ratio in the acute infection with <i>Schistosoma japonicum</i> among the three groups.</p
- …