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We present the MR properties of a novel bio-responsive phosphorus probe doped with iron for dual proton and phosphorus magnetic resonance imaging ( 1 H/ 31 P-MRI), which provide simultaneously complementary information. The probes consist of non-toxic biodegradable calcium phytate (CaIP 6 ) nanoparticles doped with different amounts of cleavable paramagnetic Fe 3+ ions. Phosphorus atoms in the phytate structure delivered an efficient 31 P-MR signal, with iron ions altering MR contrast for both 1 H and 31 P-MR. The coordinated paramagnetic Fe 3+ ions broadened the 31 P-MR signal spectral line due to the short T 2 relaxation time, resulting in more hypointense signal. However, when Fe 3+ was decomplexed from the probe, relaxation times were prolonged. As a result of iron release, intensity of 1 H-MR, as well as the 31 P-MR signal increase. These 1 H and 31 P-MR dual signals triggered by iron decomplexation may have been attributable to biochemical changes in the environment with strong iron chelators, such as bacterial siderophore (deferoxamine). Analysing MR signal alternations as a proof-of-principle on a phantom at a 4.7 T magnetic field, we found that iron presence influenced 1 H and 31 P signals and signal recovery via iron chelation using deferoxamine.

The visualization of organs and tissues using 31P magnetic resonance (MR) imaging represents an immense challenge. This is largely due to the lack of sensitive biocompatible probes required to deliver a high-intensity MR signal that can be distinguished from the natural biological background. Synthetic water-soluble phosphorus-containing polymers appear to be suitable materials for this purpose due to their adjustable chain architecture, low toxicity, and favorable pharmacokinetics. In this work, we carried out a controlled synthesis, and compared the MR properties, of several probes consisting of highly hydrophilic phosphopolymers differing in composition, structure, and molecular weight. Based on our phantom experiments, all probes with a molecular weight of ~3–400 kg·mol−1, including linear polymers based on poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC), poly(ethyl ethylenephosphate) (PEEP), and poly[bis(2-(2-(2-methoxyethoxy)ethoxy)ethoxy)]phosphazene (PMEEEP) as well as star-shaped copolymers composed of PMPC arms grafted onto poly(amidoamine) dendrimer (PAMAM-g-PMPC) or cyclotriphosphazene-derived cores (CTP-g-PMPC), were readily detected using a 4.7 T MR scanner. The highest signal-to-noise ratio was achieved by the linear polymers PMPC (210) and PMEEEP (62) followed by the star polymers CTP-g-PMPC (56) and PAMAM-g-PMPC (44). The 31P T1 and T2 relaxation times for these phosphopolymers were also favorable, ranging between 1078 and 2368 and 30 and 171 ms, respectively. We contend that select phosphopolymers are suitable for use as sensitive 31P MR probes for biomedical applications.

Contactless digital tags are increasingly penetrating into many areas of human activities. Digitalization of our environment requires an ever growing number of objects to be identified and tracked with machine-readable labels. Molecules offer immense potential to serve for this purpose, but our ability to write, read, and communicate molecular code with current technology remains limited. Here we show that magnetic patterns can be synthetically encoded into stable molecular scaffolds with paramagnetic lanthanide ions to write digital code into molecules and their mixtures. Owing to the directional character of magnetic susceptibility tensors, each sequence of lanthanides built into one molecule produces a unique magnetic outcome. Multiplexing of the encoded molecules provides a high number of codes that grows double-exponentially with the number of available paramagnetic ions. The codes are readable by nuclear magnetic resonance in the radiofrequency (RF) spectrum, analogously to the macroscopic technology of RF identification. A prototype molecular system capable of 16-bit (65,535 codes) encoding is presented. Future optimized systems can conceivably provide 64-bit (~10^19 codes) or higher encoding to cover the labelling needs in drug discovery, anti-counterfeiting and other areas. Molecules offer enormous capacity for information storage. Here, the authors show that information can be encoded into molecules with sequences of paramagnetic lanthanide ions, and decoded using nuclear magnetic resonance spectroscopy.

Tissue glues are used during surgical treatment of acute aorta dissection although some glues release toxic products and thus alter the histological structure of the vessel wall. The aim of our study was to use a porcine experimental model of infrarenal aorta dissection to compare histological changes of the vessel wall 1, 6 and 12 months after application of BioGlue, Gelatin-resorcin-formaldehyde (GRF) glue and Tissucol. For quantification, stereological methods were used. All types of glue caused stenosis, GRF most and Tissucol least severely. With increasing postoperative survival time, stenosis was again reduced. Elastine length density decreased with increasing survival time in Control as well as in all Experimental groups. The immunohistochemical phenotype of vascular smooth muscle cells was similar in Tissucol and Control samples. In GRF samples, actin, desmin and vimentin expression changed most severely. Similarly, number and distribution of vasa vasorum in the aortic wall was altered most severely in GRF samples. They tended to return to normal with increasing postoperative survival time, but at a slow rate in the GRF samples. It can be concluded that GRF causes the most severe histopathological changes within the treated aorta, which could be a reason for late failures of dissection surgery. However, glue handling and adhesive properties have to be taken into account, too, when certain glue is chosen for surgical intervention. Increased inflammation and vascularisation might even stabilise the aortic wall. Long-term experimental studies would be helpful to assess healing processes after initial disorganisation of the aortic wall structure.

The visualization of organs and tissues using [sup.31]P magnetic resonance (MR) imaging represents an immense challenge. This is largely due to the lack of sensitive biocompatible probes required to deliver a high-intensity MR signal that can be distinguished from the natural biological background. Synthetic water-soluble phosphorus-containing polymers appear to be suitable materials for this purpose due to their adjustable chain architecture, low toxicity, and favorable pharmacokinetics. In this work, we carried out a controlled synthesis, and compared the MR properties, of several probes consisting of highly hydrophilic phosphopolymers differing in composition, structure, and molecular weight. Based on our phantom experiments, all probes with a molecular weight of ~3–400 kg·mol[sup.−1], including linear polymers based on poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC), poly(ethyl ethylenephosphate) (PEEP), and poly[bis(2-(2-(2-methoxyethoxy)ethoxy)ethoxy)]phosphazene (PMEEEP) as well as star-shaped copolymers composed of PMPC arms grafted onto poly(amidoamine) dendrimer (PAMAM-g-PMPC) or cyclotriphosphazene-derived cores (CTP-g-PMPC), were readily detected using a 4.7 T MR scanner. The highest signal-to-noise ratio was achieved by the linear polymers PMPC (210) and PMEEEP (62) followed by the star polymers CTP-g-PMPC (56) and PAMAM-g-PMPC (44). The [sup.31]P T[sub.1] and T[sub.2] relaxation times for these phosphopolymers were also favorable, ranging between 1078 and 2368 and 30 and 171 ms, respectively. We contend that select phosphopolymers are suitable for use as sensitive [sup.31]P MR probes for biomedical applications.

Plectin, a highly versatile cytolinker protein, provides tissues with mechanical stability through the integration of intermediate filaments (IFs) with cell junctions. Here, we hypothesize that plectin-controlled cytoarchitecture is a critical determinant of the intestinal barrier function and homeostasis. Mice lacking plectin in an intestinal epithelial cell (IEC; PleΔIEC) spontaneously developed colitis characterized by extensive detachment of IECs from the basement membrane (BM), increased intestinal permeability, and inflammatory lesions. Moreover, plectin expression was reduced in the colons of ulcerative colitis (UC) patients and negatively correlated with the severity of colitis. Mechanistically, plectin deficiency in IECs led to aberrant keratin filament (KF) network organization and the formation of dysfunctional hemidesmosomes (HDs) and intercellular junctions. In addition, the hemidesmosomal α6β4 integrin (Itg) receptor showed attenuated association with KFs, and protein profiling revealed prominent downregulation of junctional constituents. Consistent with the effects of plectin loss in the intestinal epithelium, plectin-deficient IECs exhibited remarkably reduced mechanical stability and limited adhesion capacity in vitro. Feeding mice with a low-residue liquid diet that reduced mechanical stress and antibiotic treatment successfully mitigated epithelial damage in the PleΔIEC colon.

Syngeneic transplantation of murine aorta segments with advanced atherosclerotic lesions in defined recipients is a valuable model for regression studies. To date, this model has not been used to study the regression of initial atherosclerotic lesions. The aim of this study was to evaluate a microsurgical technique of syngeneic heterotopic transplantation of the thoracic aorta of young apolipoprotein E-deficient (ApoE-/-) mice to the abdominal aorta of wild-type recipients. Stereological quantification methods were tested in order to assess changes in structure and volume of the aortic wall including the involvement of immune cells in changes of the atherosclerotic lesions. The animals were euthanised one month after surgery and histological analysis including stereological quantification of changes in both the grafts and adjacent aorta segments was performed. The overall survival rate of the recipients was 62.5%. No regression of initial atherosclerotic lesion was achieved and neointima formation and elastin degradation prevailed in all transplanted specimens. The volume of the arteriosclerotic lesions was higher (p<0.001) and elastin length density was lower (p<0.001) in transplanted ApoE-/- samples as compared to adjacent segments. In transplanted grafts, T- and B-lymphocytes, macrophages and neutrophilic granulocytes formed non-random clusters within the vessel wall and they were colocalised with the sutures. The reproducibility of the promising regression model was derogated in young mice by the striking dependence of the results upon the operation technique. Stereological assessment has proven to be accurate, correct and reproducible; it has provided us with robust quantitative estimates, which can be achieved with a reasonable effort.

We present the MR properties of a novel bio-responsive phosphorus probe doped with iron for dual proton and phosphorus magnetic resonance imaging ( H/ P-MRI), which provide simultaneously complementary information. The probes consist of non-toxic biodegradable calcium phytate (CaIP ) nanoparticles doped with different amounts of cleavable paramagnetic Fe ions. Phosphorus atoms in the phytate structure delivered an efficient P-MR signal, with iron ions altering MR contrast for both H and P-MR. The coordinated paramagnetic Fe ions broadened the P-MR signal spectral line due to the short T relaxation time, resulting in more hypointense signal. However, when Fe was decomplexed from the probe, relaxation times were prolonged. As a result of iron release, intensity of H-MR, as well as the P-MR signal increase. These H and P-MR dual signals triggered by iron decomplexation may have been attributable to biochemical changes in the environment with strong iron chelators, such as bacterial siderophore (deferoxamine). Analysing MR signal alternations as a proof-of-principle on a phantom at a 4.7 T magnetic field, we found that iron presence influenced H and P signals and signal recovery via iron chelation using deferoxamine.

The visualization of organs and tissues using P magnetic resonance (MR) imaging represents an immense challenge. This is largely due to the lack of sensitive biocompatible probes required to deliver a high-intensity MR signal that can be distinguished from the natural biological background. Synthetic water-soluble phosphorus-containing polymers appear to be suitable materials for this purpose due to their adjustable chain architecture, low toxicity, and favorable pharmacokinetics. In this work, we carried out a controlled synthesis, and compared the MR properties, of several probes consisting of highly hydrophilic phosphopolymers differing in composition, structure, and molecular weight. Based on our phantom experiments, all probes with a molecular weight of ~3-400 kg·mol , including linear polymers based on poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC), poly(ethyl ethylenephosphate) (PEEP), and poly[bis(2-(2-(2-methoxyethoxy)ethoxy)ethoxy)]phosphazene (PMEEEP) as well as star-shaped copolymers composed of PMPC arms grafted onto poly(amidoamine) dendrimer (PAMAM- -PMPC) or cyclotriphosphazene-derived cores (CTP- -PMPC), were readily detected using a 4.7 T MR scanner. The highest signal-to-noise ratio was achieved by the linear polymers PMPC (210) and PMEEEP (62) followed by the star polymers CTP- -PMPC (56) and PAMAM-g-PMPC (44). The P and relaxation times for these phosphopolymers were also favorable, ranging between 1078 and 2368 and 30 and 171 ms, respectively. We contend that select phosphopolymers are suitable for use as sensitive P MR probes for biomedical applications.