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Methods in Molecular Biology (Clifton,... 2023Dysfunction in adipocyte expansion during the onset of obesity is associated with metabolic abnormalities. Determination of adipocyte size and number is an important...
Dysfunction in adipocyte expansion during the onset of obesity is associated with metabolic abnormalities. Determination of adipocyte size and number is an important measure for a comprehensive evaluation of the metabolic status of adipose tissue. Here, we describe three methods for the determination of adipocyte size that can be applied to tissue samples obtained from humans and rodent models. While the first method presented is more robust, it does require the use of osmium, a toxic heavy metal, which requires special handling and disposal precautions in addition to specialized equipment. Two additional methods are described that can be of use to most researchers.
Topics: Humans; Adipocytes; Adipose Tissue; Obesity
PubMed: 37076669
DOI: 10.1007/978-1-0716-3167-6_4 -
Internal Medicine (Tokyo, Japan) 2023A 32-year-old man was admitted for the evaluation of proteinuria (5.69 g/day). A light microscopic examination showed markedly dilated glomerular capillary loops with...
A 32-year-old man was admitted for the evaluation of proteinuria (5.69 g/day). A light microscopic examination showed markedly dilated glomerular capillary loops with vacuolated areas in many glomeruli, and vacuolated areas were seen on peritubular capillaries in the tubulointerstitium. When electron microscopy specimens prepared by pre-fixation with glutaraldehyde and post-fixation with osmium tetroxide were used for oil red staining, the deposition was confirmed on the affected areas. A genetic analysis of apoE showed that the lipoprotein glomerulopathy was due to apoE-Sendai (Arg145Pro, p.R163P) heterozygosity, which was found in not only the patient but also his mother and twin brother.
Topics: Male; Humans; Adult; Apolipoproteins E; Kidney Diseases; Kidney Glomerulus; Proteinuria; Heterozygote
PubMed: 37532513
DOI: 10.2169/internalmedicine.0834-22 -
Histochemistry and Cell Biology Apr 2024One hundred years ago, Robert Feulgen published a landmark paper in which he described the first method to stain DNA in cells and tissues. Although a century has passed... (Review)
Review
One hundred years ago, Robert Feulgen published a landmark paper in which he described the first method to stain DNA in cells and tissues. Although a century has passed since the discovery by Feulgen and Rossenbeck, the chemical reaction still exerts an important influence in current histochemical studies. Its contribution in diverse fields, spanning from biomedicine to plant biology, has paved the way for the most significant studies that constitute our current knowledge. The possibility to specifically explore the DNA in cell nuclei while quantifying its content makes it a contemporary and timeless method. Indeed, many histocytochemical studies following the 1924 paper have led to a deep understanding of genome organization in general as well as several specific mechanisms (e.g. DNA duplication or tumour pathology) that, nowadays, constitute some of the most fundamental pillars in biological investigations. In this review, we discuss the chemistry and application of the Feulgen reaction to both light and electron microscopy.
PubMed: 38609528
DOI: 10.1007/s00418-024-02279-9 -
Dalton Transactions (Cambridge, England... Feb 2022The reactivity of the tungsten diphenylarsinocarbyne [W(CAsPh)(CO)(Tp*)] (1; Tp* = hydrotris(dimethylpyrazolyl)borato) is described. The pyramidal arsenic coordinates...
The reactivity of the tungsten diphenylarsinocarbyne [W(CAsPh)(CO)(Tp*)] (1; Tp* = hydrotris(dimethylpyrazolyl)borato) is described. The pyramidal arsenic coordinates to a selection of 5d metal centres, forming heterobi- or trimetallic complexes with osmium(II), iridium(III), platinum(II) and gold(I). In the latter case, the WC bond provides a competitive site for gold(I) coordination. Treatment with MeOSOCF results in methylation at arsenic to give the first example of an arsoniocarbyne, [W(CAsPhCH)(CO)(Tp*)]OSCF, for which only the WC bond remains available for gold(I) coordination.
PubMed: 35019915
DOI: 10.1039/d1dt03790k -
Biomedical Materials (Bristol, England) Mar 2021With a rapid advancement of nanotechnology and the close integration of disciplines, research on nanozymes (nanomaterials with enzyme-like activities), is becoming an... (Review)
Review
With a rapid advancement of nanotechnology and the close integration of disciplines, research on nanozymes (nanomaterials with enzyme-like activities), is becoming an expeditiously developing field. In recent years, platinum group element (PGE)-based (Pt, Pd, Ru, Rh, Ir, and Os) nanozymes developed successively, have not only promoted the research of nanozymes but also expanded the biomedical applications of nanomaterials. Generally speaking, PGE-based nanozymes process high catalytic efficiency, specific surface area, stability, and other physical/chemical properties, which benefit for their applications in biosensing, biological medicine, biomedical imaging, and environmental protection. This paper will introduce the research progress of PGE-based nanozymes including their synthesis, characterization, enzyme-like activities, stability, biocompatibility, toxicity, and applications for biological detection and clinical relevance. Our emphasis is put on unfolding the roles of PGE-based nanozymes in biomedical applications and how they overcome the limitations. Last but not least, trends and future perspectives of PGE-based nanozymes in biomedical applications are also provided.
Topics: Catalysis; Nanostructures; Nanotechnology; Platinum
PubMed: 33171457
DOI: 10.1088/1748-605X/abc904 -
The Journal of Organic Chemistry Jan 2022The reactions of the N-heterocyclic carbene-phosphinidene adducts (NHC)PSiMe and (NHC)PH with the dinuclear ruthenium and osmium complexes [(η--cymene)MCl] (M = Ru, Os)...
The reactions of the N-heterocyclic carbene-phosphinidene adducts (NHC)PSiMe and (NHC)PH with the dinuclear ruthenium and osmium complexes [(η--cymene)MCl] (M = Ru, Os) afforded the half-sandwich complexes [(η--cymene){(NHC)P}MCl] and [(η--cymene){(NHC)PH}MCl] with two- and three-legged piano-stool geometries, respectively (NHC = IDipp, IMes; IDipp = 1,3-bis(2,6-diisopropylphenyl)imidazolin-2-ylidene; IMes = 1,3-bis(2,4,6-trimethylphenyl)imidazolin-2-ylidene). The complexes were initially tested as precatalysts for the hydroboration of benzonitrile, and the most active species, the ruthenium complex [(η--cymene){(IMes)P}RuCl], was further used for the efficient hydroboration of a wide range (ca. 50 substrates) of nitriles, carboxylic esters, and carboxamides in neat pinacolborane (HBpin) under comparatively mild reaction conditions (60-80 °C, 3-5 mol % catalyst loading). Preliminary mechanistic and kinetic studies are reported, and stoichiometric reactions with HBpin indicate the initial formation of the monohydride complex [(η--cymene){(IMes)P}RuH] as the putative catalytically active species.
PubMed: 35007063
DOI: 10.1021/acs.joc.1c02377 -
Inorganic Chemistry Dec 2021Half-sandwich Os-arene complexes exhibit promising anticancer activity, but their photochemistry has hardly been explored. To exploit the photocytotoxicity and...
Half-sandwich Os-arene complexes exhibit promising anticancer activity, but their photochemistry has hardly been explored. To exploit the photocytotoxicity and photochemistry of Os-arenes, -chelated complexes [Os(η--cymene)(Curc)Cl] (, Curc = curcumin) and [Os(η-biphenyl)(Curc)Cl] (), and -chelated complexes [Os(η-biphenyl)(dpq)I]PF (, dpq = pyrazino[2,3-][1,10]phenanthroline) and [Os(η-biphenyl)(bpy)I]PF (, bpy = 2,2'-bipyridine), have been investigated. The Os-arene curcumin complexes showed remarkable photocytotoxicity toward a range of cancer cell lines (blue light IC: 2.6-5.8 μM, photocytotoxicity index PI = 23-34), especially toward cisplatin-resistant cancer cells, but were nontoxic to normal cells. They localized mainly in mitochondria in the dark but translocated to the nucleus upon photoirradiation, generating DNA and mitochondrial damage, which might contribute toward overcoming cisplatin resistance. Mitochondrial damage, apoptosis, ROS generation, DNA damage, angiogenesis inhibition, and colony formation were observed when A549 lung cancer cells were treated with . The photochemistry of these Os-arene complexes was investigated by a combination of NMR, HPLC-MS, high energy resolution fluorescence detected (HERFD), X-ray adsorption near edge structure (XANES) spectroscopy, total fluorescence yield (TFY) XANES spectra, and theoretical computation. Selective photodissociation of the arene ligand and oxidation of Os(II) to Os(III) occurred under blue light or UVA excitation. This new approach to the design of novel Os-arene complexes as phototherapeutic agents suggests that the novel curcumin complex , in particular, is a potential candidate for further development as a photosensitizer for anticancer photoactivated chemotherapy (PACT).
Topics: A549 Cells; Antineoplastic Agents; Apoptosis; Calixarenes; Cell Proliferation; Cell Survival; Coordination Complexes; DNA Damage; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Humans; Molecular Structure; Osmium; Photochemical Processes
PubMed: 34503331
DOI: 10.1021/acs.inorgchem.1c00241 -
Chemical Communications (Cambridge,... Feb 2022We report a new osmium(VI) nitrido complex bearing a nonplanar tetradentate ligand with potent anticancer activity. This complex causes mitochondrial damage, which...
We report a new osmium(VI) nitrido complex bearing a nonplanar tetradentate ligand with potent anticancer activity. This complex causes mitochondrial damage, which induces liver cancer cell death oncosis and apoptosis. This is the first osmium-based anticancer candidate that induces oncosis.
Topics: Antineoplastic Agents; Apoptosis; Cell Proliferation; Coordination Complexes; Drug Screening Assays, Antitumor; Hep G2 Cells; Humans; Mitochondria; Molecular Structure; Nitriles; Osmium
PubMed: 35024704
DOI: 10.1039/d1cc05148b -
Journal of Inorganic Biochemistry Sep 2022Being identified with less toxic and generally showing selective effects for solid tumor metastases, ruthenium and osmium compounds are promising drug candidates for...
Being identified with less toxic and generally showing selective effects for solid tumor metastases, ruthenium and osmium compounds are promising drug candidates for clinical uses. Human serum proteins, such as albumin and transferrin, play vital roles in the transportation and accumulation of ruthenium and osmium agents into target tissues. However, the molecular mechanism of how transferrin transport ruthenium and their osmium analogues at atomic level remains obscure. In this study, we uncovered that the cellular uptake of Os or Ru are not competed by Fe. To unveil the molecular mechanism behind the phenomena, we report the first crystal structures of human serum transferrin (hTF) in complex with ruthenium and osmium compounds bound to the non-conserved residues on the surface of hTF without altering its overall conformation. As for Ru and Os, these binding sites by descending affinity are: His14/His289, His349-350 ~ His578/Arg581. Ruthenium drugs and their osmium analogues preferentially bind to His14/His289 with bipyridine or imidazole ligands leaving. These binding sites on hTF surface are also available in human lactoferrin and some transferrin family member of other species. The presence of these binding sites makes the cellular uptake of Ru and Os less affected by Fe, compare to Zr or Hf. Collectively, these findings are critical for our understanding of the role of serum transferrin in cellular delivery of ruthenium and osmium anticancer agents.
Topics: Binding Sites; Humans; Models, Molecular; Osmium; Osmium Compounds; Ruthenium; Transferrin
PubMed: 35690040
DOI: 10.1016/j.jinorgbio.2022.111885 -
Basic & Clinical Pharmacology &... Nov 2020Osmium tetroxide is a strong oxidizing agent used in electron microscopy. Eye exposure may cause severe burns, and after inhalation or ingestion damage to the...
Osmium tetroxide is a strong oxidizing agent used in electron microscopy. Eye exposure may cause severe burns, and after inhalation or ingestion damage to the respiratory or gastrointestinal tract occurs. Exposure to osmium and its compounds is extremely rare. We present a case of a 32-year-old female stained by 9 mL of 2% osmium tetroxide in acetone during an accident in the laboratory, with rare dermal and ocular findings. Due to lack of data in toxicological databases and the absence of antidote, the therapy was symptomatic. Osmium was detected in serum 19 hours later (0.22 μg/L) and in urine during the 15-hour collection (three samples-7.05, 1.65 and 8.45 μg/L). In blood serum on admission, after 1 and 2 days after exposure, the levels of iron (28.2, 39.8 and 50.5 μmol/L; reference range 5.8-34.5 μmol/L) and transferrin receptor/ferritine were elevated. To our knowledge, this is the first paper documenting a significant absorption from the skin and potentially from the eye conjunctiva, based on serum and urine analysis. The relationship between increased iron in blood and exposure has not been described yet, and the mechanism remains unknown. The patient is being followed up for the unknown long-term effects.
Topics: Adult; Eye; Female; Humans; Osmium Tetroxide; Skin
PubMed: 32524772
DOI: 10.1111/bcpt.13450