Project description:This Phase I clinical trial aims to evaluate the safety, tolerability, pharmacokinetics (PK) profile and preliminary efficacy of intratumoral injection of Carbon Nanoparticle-Loaded Iron [CNSI-Fe(II)] in patients with advanced solid tumors. The study also aims to observe dose-limiting toxicities (DLT) of CNSI-Fe(II) to determine the maximum tolerated dose (MTD) or the highest injectable dose in humans, providing dosing guidelines for future clinical studies. CNSI-Fe(II) shows promise as an innovative tumor therapeutic agent due to its unique properties of ferroptosis. The study primarily focuses on assessing the potential efficacy of CNSI-Fe(II) in patients with advanced solid tumors, particularly in patients with Kras mutation, e.g., pancreatic cancer patients.
Project description:Investigation of whole genome gene expression level changes in a Shewanella oneidensis MR-1 to Fe nanoparticle decorated anodes, compared to the carbon plate anodes in microbial electrolysis cells. Whole genome microarray analysis of the gene expression showed that the encoding biofilm formation genes were significantly up-regulated as response to nanoparticle decorated anodes which indicated thickness improvements contributed to enhance current density. The increased expression genes related to nanowire, flavins and c-type cytochromes also have partially contributed to enhance current density by Fe nanoparticle decorated anode. The majority of additional differentially expressed genes associated with electron transport, anaerobic metabolism in response to the nanostructured anodes possibly play roles in current density enhancement. A six chip study using total RNA recovered from three separate replicates of biofilm on Fe Nanoparticle decorated anode of Shewanella oneidensis MR-1 and three separate replicates of carbon plate control. Each chip measures the expression level of 4,295 genes .
Project description:Investigation of whole genome gene expression level changes in a Shewanella oneidensis MR-1 to Fe nanoparticle decorated anodes, compared to the carbon plate anodes in microbial electrolysis cells. Whole genome microarray analysis of the gene expression showed that the encoding biofilm formation genes were significantly up-regulated as response to nanoparticle decorated anodes which indicated thickness improvements contributed to enhance current density. The increased expression genes related to nanowire, flavins and c-type cytochromes also have partially contributed to enhance current density by Fe nanoparticle decorated anode. The majority of additional differentially expressed genes associated with electron transport, anaerobic metabolism in response to the nanostructured anodes possibly play roles in current density enhancement.
Project description:Iron is an essential nutrient for the opportunistic pathogen Pseudomonas aeruginosa, as for almost all living organisms. To access this element, the pathogen is able to express at least 15 different iron-uptake pathways, the vast majority involving small iron chelators called siderophores. Indeed, P. aeruginosa produces two siderophores, pyoverdine and pyochelin, but can also use many produced by other microorganisms. This implies that the bacterium expresses appropriate TonB-dependent transporters (TBDTs) at the outer membrane to import the ferric form of each of the siderophores used. These transporters are highly selective for a given ferri-siderophore complex or for siderophores with similar chemical structures. Here, we show that P. aeruginosa can also use rhizoferrin, staphyloferrin A, aerobactin, and schizokinen as siderophores to access iron. Growth assays in iron-restricted conditions and 55Fe uptake assays showed that the two alpha-carboxylate type siderophores rhizoferrin-Fe and staphyloferrin A-Fe are transported into P. aeruginosa cells by the TBDT ActA (PA3268). Among the mixed alpha-carboxylate/hydroxamate type siderophores, we found aerobactin-Fe to be transported by ChtA (as previously described) and schizokinen-Fe by ChtA and another unidentified TBDT.
Project description:Fe-IMAC columns for robust and reproducible phosphopeptide ernichment, comparison to TiO2 batch and Ti-IMAC tip enrichment, large scale phosphoproteomics coupling Fe-IMAC column pre-enrichment to subsequent hSAX separation
Project description:Iron is an essential nutrient for bacterial growth but poorly bioavailable. To scavenge ferric iron present in their environment, bacteria synthesize and secrete siderophores, small compounds with a high affinity for iron. Pyochelin (PCH) is one of the two siderophores produced by the opportunistic pathogen Pseudomonas aeruginosa. Once having captured a ferric iron, PCH-Fe is imported back into bacteria first by the outer membrane transporter FptA and afterwards by the inner membrane permease FptX. Here using molecular biology, 55Fe uptake assays and LC-MS/MS quantification of PCH in the different bacterial cell fractions, we show that (i) PCH (probably under its PCH-Fe form) is able to rich bacterial periplasm and cytoplasm when both FptA and FptX are expressed, and (ii) that PchHI (a heterodimeric ABC transporter) plays a role in the translocation of siderophore-free iron siderophore-free iron across the inner membrane into the cytoplasm. Consequently, probably the first fraction of PCH-Fe internalized by FptA may be transported further by FptX in the bacterial cytoplasm to activate the transcriptional regulator PchR, regulating the transcription of all genes of the PCH pathway. The further fractions of PCH-Fe transported by FptA may dissociate in the bacterial periplasm by an unknown mechanism, with the siderophore-free iron being transported into the cytoplasm by PchHI.