BACKGROUND: Chondrosarcomas are rare malignant bone tumors diagnosed by analyzing radiological images and histology of tissue biopsies and evaluating features such as matrix calcification, cortical destruction, trabecular penetration, and tumor cell entrapment.
METHODS: We retrospectively analyzed 16 cartilaginous tumor tissue samples from three patients (51-, 54-, and 70-year-old) diagnosed with a dedifferentiated chondrosarcoma at the femur, a moderately differentiated chondrosarcoma in the pelvis, and a predominantly moderately differentiated chondrosarcoma at the scapula, respectively. We combined a hematein-based x-ray staining with high-resolution three-dimensional (3D) microscopic x-ray computed tomography (micro-CT) for nondestructive 3D tumor assessment and tumor margin evaluation.
RESULTS: We detected trabecular entrapment on 3D micro-CT images and followed bone destruction throughout the volume. In addition to staining cell nuclei, hematein-based staining also improved the visualization of the tumor matrix, allowing for the distinction between the tumor and the bone marrow cavity. The hematein-based staining did not interfere with further conventional histology. There was a 5.97 ± 7.17% difference between the relative tumor area measured using micro-CT and histopathology (p = 0.806) (Pearson correlation coefficient r = 0.92, p = 0.009). Signal intensity in the tumor matrix (4.85 ± 2.94) was significantly higher in the stained samples compared to the unstained counterparts (1.92 ± 0.11, p = 0.002).
CONCLUSIONS: Using nondestructive 3D micro-CT, the simultaneous visualization of radiological and histopathological features is feasible.
CONCLUSIONS: 3D micro-CT data supports modern radiological and histopathological investigations of human bone tumor specimens. It has the potential for being an integrative part of clinical preoperative diagnostics.
CONCLUSIONS: • Matrix calcifications are a relevant diagnostic feature of bone tumors. • Micro-CT detects all clinically diagnostic relevant features of x-ray-stained chondrosarcoma. • Micro-CT has the potential to be an integrative part of clinical diagnostics.

BACKGROUND: Okadaic acid (OA) and hematein are both able to inhibit the proliferation of human lung adenocarcinoma A549 cells. However, it is largely unknown about their combined effects on proliferation and apoptosis of A549 cells.
METHODS: The combined effects of the two drugs on proliferation of A549 cells and the responses of mitochondria and endoplasmic reticulum (ER) apoptosis pathways were investigated.
RESULTS: MTT assay showed that both OA and hematein significantly inhibited proliferation of A549 cells, and the combined drugs could further increase the inhibition ratio with lower dosages. Inverted phase contrast microscope and scanning electron microscope (SEM) analysis indicated that the combined drugs aggravated the appearance of apoptotic bodies and damaged cells. Compared to the single drug treated groups, reactive oxygen species (ROS) contents were significantly higher in the groups treated by the combined drugs, and mitochondrial membrane potential was significant lower. Western blot indicated that pro-apoptotic Bax that involved in mitochondrial apoptosis pathway increased, the anti-apoptotic protein Bcl-2 decreased, and the ER apoptosis-related proteins CHOP, Calpain2, JNK1 and IRE1 increased.
CONCLUSIONS: This work demonstrates that OA combined hematein can more effectively inhibit proliferation of A549 cells, and induce apoptosis of A549 cells via mitochondria and ER dependent pathways.

The tetracyclic phenolic compound brazilin, derived from the wood of Caesalpinia sappan, has been shown to bind to the chromatin protein BAF1 (barrier-to-autointegration factor 1), a protein essential to maintain integrity of the nuclear envelope in cells. BAF1 plays a role in cancer development. Using molecular docking, we have located the binding site for brazilin on the surface of the BAF1 monomer and compared its binding to that of four analogs. The oxidized product brazilein (ΔE = -57.7 kcal/mol) exhibits a higher affinity for BAF1 compared to the reduced form brazilin (ΔE = -38.2 kcal/mol). Incorporation of a 4-hydroxyl substituent on the indenochromene unit affords hematoxylin and hematein. In silico analysis predicts that the oxidized form hematein (ΔE = -66.2 kcal/mol) displays a higher affinity for BAF1 than the reduced form hematoxylin (ΔE = -42.2 kcal/mol). In contrast, the atypical bis-lactone product brazilide A cannot form good complexes with BAF1. The analysis points to the formation of more stable BAF1 complexes with the oxidized molecules compared to the reduced ones, but the position of the binding site on the protein cavity is different for brazilin/hematoxylin compared to brazilein/hematein. Our study may be useful to guide the design of BAF1 ligands.

The vast majority of therapeutic approaches tested so far for prion diseases, transmissible neurodegenerative disorders of human and animals, tackled PrPSc , the aggregated and infectious isoform of the cellular prion protein (PrPC ), with largely unsuccessful results. Conversely, targeting PrPC expression, stability or cell surface localization are poorly explored strategies. We recently characterized the mode of action of chlorpromazine, an anti-psychotic drug known to inhibit prion replication and toxicity by inducing the re-localization of PrPC from the plasma membrane. Unfortunately, chlorpromazine possesses pharmacokinetic properties unsuitable for chronic use in vivo, namely low specificity and high toxicity. Here, we employed HEK293 cells stably expressing EGFP-PrP to carry out a semi-automated high content screening (HCS) of a chemical library directed at identifying non-cytotoxic molecules capable of specifically relocalizing PrPC from the plasma membrane as well as inhibiting prion replication in N2a cell cultures. We identified four candidate hits inducing a significant reduction in cell surface PrPC , one of which also inhibited prion propagation and toxicity in cell cultures in a strain-independent fashion. This study defines a new screening method and novel anti-prion compounds supporting the notion that removing PrPC from the cell surface could represent a viable therapeutic strategy for prion diseases.

Previous investigators have disagreed about whether hemalum stains DNA or its associated nucleoproteins. I review here the literature and describe new experiments in an attempt to resolve the controversy. Hemalum solutions, which contain aluminum ions and hematein, are routinely used to stain nuclei. A solution containing 16 Al3+ ions for each hematein molecule, at pH 2.0-2.5, provides selective progressive staining of chromatin without cytoplasmic or extracellular \"background color.\" Such solutions contain a red cationic dye-metal complex and an excess of Al3+ ions. The red complex is converted to an insoluble blue compound, assumed to be polymeric, but of undetermined composition, when stained sections are blued in water at pH 5.5-8.5. Staining experiments with DNA, histone and DNA + histone mixtures support the theory that DNA, not histone, is progressively colored by hemalum. Extraction of nucleic acids, by either a strong acid or nucleases at near neutral pH, prevented chromatin staining by a simple cationic dye, thionine, pH 4, and by hemalum, with pH adjustments in the range, 2.0-3.5. Staining by hemalum at pH 2.0-3.5 was not inhibited by methylation, which completely prevented staining by thionine at pH 4. Staining by hemalum and other dye-metal complexes at pH ≤ 2 may be due to the high acidity of DNA-phosphodiester (pKa ~ 1). This argument does not explain the requirement for a much higher pH to stain DNA with those dyes and fluorochromes not used as dye-metal complexes. Sequential treatment of sections with Al2(SO4)3 followed by hematein provides nuclear staining that is weaker than that attainable with hemalum. Stronger staining is seen if the pH is raised to 3.0-3.5, but there is also coloration of cytoplasm and other materials. These observations do not support the theory that Al3+ forms bridges between chromatin and hematein. When staining with hematein is followed by an Al2(SO4)3 solution, there is no significant staining. Taken together, the results of my study indicate that the red hemalum cation is electrostatically attracted to the phosphate anion of DNA. The bulky complex cation is too large to intercalate between base pairs of DNA and is unlikely to fit into the minor groove. The short range van der Waals forces that bind planar dye cations to DNA probably do not contribute to the stability of progressive hemalum staining. The red cation is precipitated in situ as a blue compound, insoluble in water, ethanol and water-ethanol mixtures, when a stained preparation is blued at pH > 5.5.

Fe- and Fe/Cu-based logwood inks were synthesized following recipes in nineteenth and early twentieth century manuals and were characterized by EPR, ESI-MS, FTIR, and Raman spectroscopies. This multi-technique approach allowed us to shed light on the structures of the complexes responsible for the inks\' colors and to obtain vibrational signatures that can be used to identify the different inks in works of art and in historic documents. Information on the nature and chemical properties of the complexes formed between a dye and a mordant is important as these determine, at least in part, their lightfastness. EPR permitted to determine the coordination environment of the metallic ions. The results of the ESI-MS analysis demonstrated, for the first time, the breakdown of the hematein molecule during the ink preparation, and that the colorants are formed by the complexation of the metallic ions by hematein breakdown products, mainly catechol and/or bicyclic compounds. The FTIR spectra obtained were found to be dominated by bands due to the binding medium and sulfates used as reagents. The Raman analysis showed that the characteristic features for the different inks studied depend on the historic recipe used, attesting to the challenges that their identification and characterization in works of art present. In the Raman spectra of the inks applied on paper, broadening of bands in the 750-400 cm(-1) range are observed when compared to the spectra of the inks\' powders, possibly due to the interaction of the compounds with the cellulose in the substrate.

In this study, we reported on a low detection limit penicillin biosensor with layer-by-layer (LbL) film containing single-graphene nanosheets (SGNs) preadsorbed with hematein, ionic liquids (ILs) and penicillinase. The penicillinase catalyzes the hydrolysis of penicillin to penicilloic acid, where H(+) is liberated and monitored amperometrically with hematein as a pH indicator. The SGN-hematein/ILs/penicillinase biosensor exhibited excellent performance for penicillin in PBS with a wide range from 1.25×10(-13) to 7.5×10(-3)M, and a low detection limit of 10(-13)M (0.04ppt, S/N≥3). Furthermore, the detection of penicillin concentration in real sample (milk) had acceptable accuracy with the assay system.