-
Carbohydrate Research Dec 2023Bacterial natural products containing heptosides such as septacidin represent interesting scaffolds for the development of drugs to combat antimicrobial resistance....
Bacterial natural products containing heptosides such as septacidin represent interesting scaffolds for the development of drugs to combat antimicrobial resistance. However, very few synthetic strategies have been reported to grant access to these derivatives. Here, we have devised a synthetic pathway to l-glycero-l-glucoheptoside, a key building block en route to septacidin, directly from l-glucose. Importantly, we show that carbon homologation at C6, encompassing oxidation of the C6-OH followed by methylenation, is significantly influenced by the nature of the C4-moiety. In order to observe the effect of various patterns, namely azide (N), p-methoxybenzyloxy (OPMB), and benzyloxy (OBn), a thorough analysis was conducted on the corresponding l-glucosides. The results unveiled a distinct trend where the efficiency of methylenation followed the trend OBn > OPMB > N. Finally, the C6-alkene was dihydroxylated in the presence of osmium tetroxide to yield the expected l/d-glycero-l-glucoheptosides. The lead building block, which features a C-4 azide, was delivered as a phenyl thioglycoside. Added to the suitable masking of the 6,7-diol, this combination enables further functionalization to achieve versatile compounds of biological interest. The study insights into the interplay between substitution at C-4 and carbon homologation at C-6 provide valuable guidance for future endeavors in the synthesis of these carbohydrate molecules.
Topics: Glucose; Azides; Heptoses; Carbon
PubMed: 38016254
DOI: 10.1016/j.carres.2023.108985 -
Chemical Science Nov 2023Photodynamic therapy (PDT) is a medical technique for the treatment of cancer. It is based on the use of non-toxic molecules, called photosensitizers (PSs), that become...
Photodynamic therapy (PDT) is a medical technique for the treatment of cancer. It is based on the use of non-toxic molecules, called photosensitizers (PSs), that become toxic when irradiated with light and produce reactive oxygen specious (ROS) such as singlet oxygen (O). This light-induced toxicity is rather selective since the physician only targets a specific area of the body, leading to minimal side effects. Yet, a strategy to improve further the selectivity of this medical technique is to confine the delivery of the PS to cancer cells only instead of spreading it randomly throughout the body prior to light irradiation. To address this problem, we present here novel sulfonamide-based monopodal and dipodal ruthenium and osmium polypyridyl complexes capable of targeting carbonic anhydrases (CAs) that are a major target in cancer therapy. CAs are overexpressed in the membrane or cytoplasm of various cancer cells. We therefore anticipated that the accumulation of our complexes in or outside the cell prior to irradiation would improve the selectivity of the PDT treatment. We show that our complexes have a high affinity for CAs, accumulate in cancer cells overexpressing CA cells and importantly kill cancer cells under both normoxic and hypoxic conditions upon irradiation at 540 nm. More importantly, Os(ii) compounds still exhibit some phototoxicity under 740 nm irradiation under normoxic conditions. To our knowledge, this is the first description of ruthenium/osmium-based PDT PSs that are CA inhibitors for the selective treatment of cancers.
PubMed: 37920359
DOI: 10.1039/d3sc03932c -
Asian Biomedicine : Research, Reviews... Oct 2023Hemolysis, elevated liver enzymes, low platelet count (HELLP) syndrome is generally considered to be a variant or complication of preeclampsia. It is a life-threatening...
BACKGROUND
Hemolysis, elevated liver enzymes, low platelet count (HELLP) syndrome is generally considered to be a variant or complication of preeclampsia. It is a life-threatening obstetric complication.
OBJECTIVES
To evaluate the immunohistochemistry and ultrastructural of syncytiotrophoblastand Hoffbauer cells in placental villi of patients with HELLP syndrome.
METHODS
Two groups of patients with a total of 50 full-term human placentas (n = 25 in each group) were assigned as the control (normotensive) and HELLP syndrome. Placental tissue samples were fixed in 10% neutral formalin and paraffin-embedding protocol was performed. We prepared 5 μm sections for histological and immunohistochemical staining. Sections were immunostained with Hoffbauer cell marker CD68. For transmission electron microscopy (TEM), placental tissue samples were fixed in 2.5% buffered glutaraldehyde and then, in 1% osmium tetroxide for routine ultrastructural examinations.
RESULTS
When the HELLP group fetal placental sections were examined, intracytoplasmic edema in syncytiotrophoblast, degenerative vacuoles, and degenerative findings on cell surface membranes were observed. Moreover, villous edema was remarkable. The number of CD68-positive Hoffbauer cells per villus control group sections was 0.23 ± 0.02 and the number of CD68-positive cells per villus in HELLP group placenta sections was 0.83 ± 0.12. The increase in the number of Hoffbauer cells per villus in the HELLP group was significant ( < 0.001). Compared with the control group, there was a significant increase in the number of Hoffbauer cells and syncytiotrophoblasts in the HELLP group, and degenerative changes were also observed in the ultrastructure of these cells.
CONCLUSIONS
Pathology of the HELLP syndrome is in relation to CD68-positive placental macrophages.
PubMed: 37899759
DOI: 10.2478/abm-2023-0065 -
ACS Organic & Inorganic Au Oct 2023The influence of fluorinated substituents on the luminescent properties of rhenium-oxo, osmium-nitrido, and gold triarylcorroles was studied via a comparison of four...
The influence of fluorinated substituents on the luminescent properties of rhenium-oxo, osmium-nitrido, and gold triarylcorroles was studied via a comparison of four ligands: triphenylcorrole (TPC), tris(-trifluoromethylphenyl)corrole (TCFPC), tris{3,5-bis(trifluoromethyl)phenyl}corrole (T3,5-CFPC), and tris(pentafluorophenyl)corrole (TPFPC). For each metal series examined, fluorinated substituents were found to enhance the luminescent properties, with the phosphorescence quantum yields and triplet decay times increasing in the order TPC < TCFPC < T3,5-CFPC < TPFPC. Among the 11 complexes examined, the highest phosphorescence quantum yield, 2.2%, was recorded for Re[TPFPC](O).
PubMed: 37810408
DOI: 10.1021/acsorginorgau.3c00016 -
BioRxiv : the Preprint Server For... Sep 2023Mapping the complete synaptic connectivity of a mammalian brain would be transformative, revealing the pathways underlying perception, behavior, and memory. Serial...
Mapping the complete synaptic connectivity of a mammalian brain would be transformative, revealing the pathways underlying perception, behavior, and memory. Serial section electron microscopy, via membrane staining using osmium tetroxide, is ideal for visualizing cells and synaptic connections but, in whole brain samples, faces significant challenges related to chemical treatment and volume changes. These issues can adversely affect both the ultrastructural quality and macroscopic tissue integrity. By leveraging time-lapse X-ray imaging and brain proxies, we have developed a 12-step protocol, ODeCO, that effectively infiltrates osmium throughout an entire mouse brain while preserving ultrastructure without any cracks or fragmentation, a necessary prerequisite for constructing the first comprehensive mouse brain connectome.
PubMed: 37808722
DOI: 10.1101/2023.09.26.558265 -
BioRxiv : the Preprint Server For... Sep 2023Scanning electron microscopy (SEM) offers an unparalleled view of the membrane topography of mammalian cells by using a conventional osmium (OsO) and ethanol-based...
Scanning electron microscopy (SEM) offers an unparalleled view of the membrane topography of mammalian cells by using a conventional osmium (OsO) and ethanol-based tissue preparation. However, conventional SEM methods limit optimal resolution due to ethanol and lipid interactions and interfere with visualization of fluorescent reporter proteins. Therefore, SEM correlative light and electron microscopy (CLEM) has been hindered by the adverse effects of ethanol and OsO on retention of fluorescence signals. To overcome this technological gap in achieving high-resolution SEM and retain fluorescent reporter signals, we developed a freeze-drying method with gaseous nitrogen (FDGN). We demonstrate that FDGN preserves cyto-architecture to allow visualization of detailed membrane topography while retaining fluorescent signals and that FDGN processing can be used in conjunction with a variety of high-resolution imaging systems to enable collection and validation of unique, high-quality data from these approaches. In particular, we show that FDGN coupled with high resolution microscopy provided detailed insight into viral or tumor-derived extracellular vesicle (TEV)-host cell interactions and may aid in designing new approaches to intervene during viral infection or to harness TEVs as therapeutic agents.
PubMed: 37808646
DOI: 10.1101/2023.09.28.559906 -
Scientific Reports Oct 2023We have successfully synthesized three osmium-based hexagonal Laves compounds ROs (R = Sc, Y, Lu), and discussed their physical properties. LeBail refinement of pXRD...
We have successfully synthesized three osmium-based hexagonal Laves compounds ROs (R = Sc, Y, Lu), and discussed their physical properties. LeBail refinement of pXRD data confirms that all compounds crystallize in the hexagonal centrosymmetric MgZn-type structure (P6/mmc, No. 194). The refined lattice parameters are a = b = 5.1791(1) Å and c = 8.4841(2) Å for ScOs, a = b = 5.2571(3) Å and c = 8.6613(2) Å for LuOs and a = b = 5.3067(6) Å and c = 8.7904(1) Å for YOs. ROs Laves phases can be viewed as a stacking of kagome nets interleaved with triangular layers. Temperature-dependent magnetic susceptibility, resistivity and heat capacity measurements confirm bulk superconductivity at critical temperatures, T, of 5.36, 4.55, and 3.47 K for ScOs, YOs, and LuOs, respectively. We have shown that all investigated Laves compounds are weakly-coupled type-II superconductors. DFT calculations revealed that the band structure of ROs is intricate due to multiple interacting d orbitals of Os and R. Nonetheless, the kagome-derived bands maintain their overall shape, and the Fermi level crosses a number of bands that originate from the kagome flat bands, broadened by interlayer interaction. As a result, ROs can be classified as (breathing) kagome metal superconductors.
PubMed: 37794026
DOI: 10.1038/s41598-023-43621-w -
Heliyon Sep 2023Cochlear implants (CIs) allow individuals with profound hearing loss to understand speech and perceive sounds. However, not all patients obtain the full benefits that...
Cochlear implants (CIs) allow individuals with profound hearing loss to understand speech and perceive sounds. However, not all patients obtain the full benefits that CIs can provide and the cause of this disparity is not fully understood. One possible factor for the variability in outcomes after cochlear implantation, is the development of fibrotic scar tissue around the implanted electrode. It has been hypothesised that limiting the extent of fibrosis after implantation may improve overall CI function, and longevity of the device. Currently, histology is often used to quantify the extent of intracochlear tissue growth after implantation however this method is labour intensive, time-consuming, often involves significant user bias, and causes physical distortion of the fibrosis. Therefore, this study aimed to evaluate x-ray micro computed tomography (μCT) as a method to measure the amount and distribution of fibrosis in a guinea pig model of cochlear implantation. Adult guinea pigs were implanted with an inactive electrode, and cochleae harvested eight weeks later (n = 7) and analysed using μCT, to quantify the extent of tissue reaction, followed by histological analysis to confirm that the tissue was indeed fibrotic. Cochleae harvested from an additional six animals following implantation were analysed by μCT, before and after contrast staining with osmium tetroxide (OsO), to enhance the visualisation of soft tissues within the cochlea, including the tissue reaction. Independent analysis by two observers showed that the quantification method was robust and provided additional information on the distribution of the response within the cochlea. Histological analysis revealed that μCT visualised dense collagenous material and new bone formation but did not capture loose, areolar fibrotic tissue. Treatment with OsO significantly enhanced the visible tissue reaction detected using μCT. Overall, μCT is an alternative and reliable method that can be used to quantify the extent of the CI-induced intracochlear tissue response and will be a useful tool for the assessment of novel anti-fibrotic treatments.
PubMed: 37662829
DOI: 10.1016/j.heliyon.2023.e19343 -
Organic Letters Aug 2023A novel stereoselective synthetic approach to pentahydroxyazepane iminosugars is described. The strategy relies on a key osmium-catalyzed aminohydroxylation reaction of...
A novel stereoselective synthetic approach to pentahydroxyazepane iminosugars is described. The strategy relies on a key osmium-catalyzed aminohydroxylation reaction of allylic alcohols obtained via addition of vinylmagnesium bromide to a d-mannose-derived aldehyde, which forms the new C-N bond with complete regio- and stereocontrol according to the tethering approach. Subsequent intramolecular reductive amination afforded the desired azepanes. This method represents the first application of the osmium-catalyzed tethered aminohydroxylation reaction to the synthesis of iminosugars.
PubMed: 37515782
DOI: 10.1021/acs.orglett.3c02087 -
Antioxidants (Basel, Switzerland) Jul 2023Altered levels of heavy metals and essential elements have been associated with oxidative stress (OS) and metabolic and hormonal changes in women with polycystic ovary... (Review)
Review
Altered levels of heavy metals and essential elements have been associated with oxidative stress (OS) and metabolic and hormonal changes in women with polycystic ovary syndrome (PCOS). We aimed to summarize the knowledge on the association of heavy metals and essential elements with OS in PCOS. An electronic literature search using PubMed for studies published between January 2008 and April 2023 was conducted. We evaluated heavy metals and essential elements in relation to OS in PCOS in 15 articles. PCOS women had increased antimonium (Sb), cadmium (Cd), lead (Pb), mercury (Hg), arsenic (As), tellurium (Te), thallium (Tl) and osmium (Os) blood levels and decreased zinc (Zn) blood levels; the results of copper (Cu) blood levels were conflicting. Some studies showed a significant correlation between heavy metals (Sb, Cd, Pb, Hg, As, Te and Tl) and essential elements (Se, Zn, Cr, Ca, Mg and Cu) and markers of OS and chronic inflammation. Heavy metals (Sb, Cd, Pb and Hg) and essential elements (Zn, Cr, Se, Ca, Mg and Cu) were associated with metabolic and hormonal characteristics in PCOS. There might be a possible benefit from supplementation therapy in reducing OS and endocrinological problems related to PCOS. Our review confirmed an association between heavy metals and essential elements with OS in PCOS women. This systematic review is registered in PROSPERO under number CRD42023418453.
PubMed: 37507937
DOI: 10.3390/antiox12071398