Concurrent cerebral infarction and intracranial tuberculoma induced by the carotid plaque complicated with miliary tuberculosis.

Cerebrovascular complications of central nervous system tuberculosis (TB) are predictors of poor prognosis and adverse outcomes. These complications are mainly intracranial arterial involvement, with occasional venous involvement. Here, we present a 67-year-old woman with concurrent cerebral infarction and intracranial tuberculoma induced by the carotid plaque complicated by miliary tuberculosis. Mycobacterium tuberculosis was observed on the luminal side of the carotid plaques in pathological specimens. Treatment with anti-TB drugs alone would likely not cure the patient, as M. tuberculosis would continue to disseminate. Endarterectomy could directly remove the embolic source, and a complete cure was achieved.

The prognosis and treatment effectiveness of de novo aneurysm formation after radiation therapy for brain tumor.

Radiation therapy is a well-established, minimally invasive method of treating brain tumors. In recent years, the number of post-radiotherapy patients has increased, and delayed side effects are evident. De novo aneurysm formation after radiation often manifests as fatal subarachnoid hemorrhage (SAH), resulting in severe clinical outcomes. Nevertheless, the prognosis and therapeutic efficacy of radiation-induced aneurysms (RIAs) remain unclear. Using the PubMed database from 1980 to 2021, we screened 45 articles (53 individual cases) on RIAs; approximately 70% of RIAs were diagnosed after rupture. Of 38 ruptured RIAs, 12 (31.6%) had modified Rankin scale (mRS) 5-6. On the other hand, all unruptured RIAs (15 cases) recovered without neurological deficits (p = 0.012). Ten of the 39 ruptured RIAs were treated surgically, and 22 were treated endovascularly. There was no significant difference in mRS between treatment modalities (p = 0.393), but conservative therapy was significantly related to unfavorable outcomes (p = 0.025). To improve clinical outcomes, RIAs need to be diagnosed before rupture. Surgeons should be aware of de novo aneurysm formation in patients long after radiation therapy.

Dynamic cyclen-metal complexes for molecular sensing and chirality signaling.

Structural dynamism plays important roles in artificial and biological systems, because it controls structures and functions of various molecules and assemblies. In this review, molecular recognition and self-assembling behavior of dynamic armed cyclen-metal complexes are discussed at the molecular and supramolecular levels. These metal complexes provide useful platforms for molecular receptors, supramolecules, and molecular assemblies that can respond rapidly to guest molecules and environments. Since armed cyclens have many structural and geometrical variations, they form a wide variety of metal complexes having specific sensing and signaling functions. The Lewis acidity of the metal cations plays an essential role in anion binding and in hydrolytic catalysis of phosphate esters. Characteristic luminescence and magnetic properties of lanthanides also enable techniques for effective bio-imaging. They also serve as chiral building blocks for self-assembled architectures, which offer chirality integration effective for chirality sensing and signaling at the supramolecular level.

Chirality transfer in propeller-shaped cyclen-calcium(II) complexes: metal-coordinating and ion-pairing anion procedures.

A series of quadruple-stranded Na(+) and Ca(2+) complexes with octadentate cyclen ligands was synthesized to produce complexes that contained four different side-arm combinations (one triazole-coumarin group and three pyridine groups (1), four pyridine groups (2), one triazole-coumarin group and three quinoline groups (3), and four quinoline groups (4)). X-ray crystallographic analysis revealed that no significant changes occurred in the stereostructure of these complexes upon replacing one pyridine group with a triazole-coumarin moiety, or by replacing Na(+) ions with Ca(2+) ions, although the coordination number of the complexes in the solid state decreased when pyridine groups were replaced by quinoline groups. In solution, all of the side arms were arranged in a propeller-like pattern to yield an enantiomer pair of Δ and Λ forms in each metal complex. The addition of a tert-butoxycarbonyl (Boc)-protected amino acid anion, that is, a coordinative chiral carboxylate anion, to the cyclen-Ca(2+) complex induced circular dichroism (CD) signals in the aromatic region by forming a 1:1 mixture of diastereomeric ternary complexes with opposite complex chirality, whilst the corresponding Na(+) complexes rarely showed any response. In complexes 1-Ca(2+) and 3-Ca(2+), this chirality-transfer process was efficiently followed by considering the induction of the CD signals at two different wavelengths, that is, the coumarin-chromophore region and the aza-aromatic region. The sign and intensity of the CD signal were significantly dependent on both the nature of the aza-aromatic moiety and the enantiomeric purity of the external anion. These Ca(2+) complexes worked as effective probes for the determination of the enantiomeric excess of the chiral anion. The cyclen-Ca(2+) complexes also interacted with the non-coordinative Δ-TRISPHAT anion through an ion-pairing mechanism to achieve chirality transfer from the anion to the metal complex; both complexes 1-Ca(2+) and 3-Ca(2+) clearly showed induced CD signals in the coumarin-chromophore region, owing to ion-paring interactions with the Δ-TRISPHAT anion. Thus, the proper combination of an octadentate cyclen ligand and a metal center demonstrated effective chirality transfer.

Luminescent lanthanide complexes as analytical tools in anion sensing, pH indication and protein recognition.

Although lanthanide complexes are recently used in luminescence labeling of bio-targets, this review focuses on sensing profiles of synthetic and biological lanthanide complexes. Rational design and combinatorial screening approaches toward synthetic lanthanide complexes applicable as luminescent sensing materials are described. Iron-carrying transferrin and ferritin proteins further form lanthanide complexes working as pH indicators and protein recognition reagents.

Mixed-metal complexes incorporating platinum and lanthanide centers for selective binding and chirality sensing of succinates.

A chromophoric platinum complex was combined with a nonacoordinated cyclen-lanthanide complex to give a new series of mixed-metal receptors. They specifically formed 1:1 complexes with dicarboxylates and offered selective chirality sensing of succinates.

Langmuir monolayers of a cholesterol-armed cyclen complex that can control enantioselectivity of amino acid recognition by surface pressure.

The cholesterol-armed cyclen Na(+) complex formed stable Langmuir monolayers at the air-water interface. The π-A isotherm displayed a reasonable limiting molecular area of ∼1.57 nm(2) and the areas expanded when amino acids were dissolved in water, indicating the efficient accommodation in the monolayers. Brewster angle microscopy (BAM) images exhibited almost no defects of the compressed Langmuir monolayers regardless of the presence of amino acids. Based on the idea that the increase in the limiting molecular areas corresponds to the amount of the adsorbed amino acid, the binding constants of three enantiomeric amino acids, namely valine (Val), leucine (Leu), and phenylalanine (Phe), were calculated at different surface pressures. Remarkably, a surface pressure dependent enantioselectivity of amino acid recognition was observed. Upon compression of the monolayers, the binding constants of amino acids increased accompanying an inversion of chiral selectivity from the D- to L-form in the case of Val and, conversely, from L- to D-form in the case of Phe.

One-pot analysis of enantiomeric excess of free amino acids by electrospray ionization mass spectrometry.

An electrospray ionization mass spectrometric method for the simultaneous analysis of the enantiomeric excess of free amino acids, without chromatographic separation, was demonstrated using a quasi-racemic mixture of deuterium-labelled and unlabelled chiral copper(ii) complexes. This convenient method enables the simultaneous high-sensitivity determination of the enantiomeric excess of 12 amino acids.

Mechanical tuning of molecular recognition to discriminate the single-methyl-group difference between thymine and uracil.

Construction of enzyme-like artificial cavities is a complex and challenging subject. Rather than synthesizing complicated host molecules, we have proposed mechanical adaptation of relatively simple hosts within dynamic media to determine the optimum conformation for molecular recognition. Here we have applied this concept to one of the most challenging biomolecular recognition problems, i.e., that of discriminating thymine from uracil. We synthesized the novel cholesterol-armed triazacyclononane as a host molecule and subjected it to structural tuning by compression of its Langmuir monolayers in the absence and in the presence of Li(+) cations in the subphase. Experimental results confirm that the monolayer of triazacyclononane host selectively recognizes uracil over adenine (ca. 7 times based on the binding constant) and thymine (ca. 64 times) under optimized conditions ([LiCl] = 10 mM at surface pressure of 35 mN m(-1)). The concept of mechanical tuning of a host structure for optimization of molecular recognition offers a novel methodology in host-guest chemistry as an alternative to the more traditional molecular design strategies.

Poly(arginine)-selective coprecipitation properties of self-assembling apoferritin and Its Tb(3+) complex: a new luminescent biotool for sensing of poly(arginine) and its protein conjugates.

The apoferritin protein and apoferritin-Tb(3+) complex were demonstrated to form oligomeric and polymeric self-assemblies in neutral aqueous solutions, based on characterization by using luminescence and UV/Vis spectroscopy, dynamic light scattering, and transmission electron microscopy. Addition of a 20-mer or higher poly(arginine) to the solution resulted in coprecipitation through nanoscale interactions, while biological proteins and other poly(amino acids) rarely yielded precipitates under the conditions employed. The apoferritin-Tb(3+) complex assembly exhibited a particularly long-lived green luminescence in aqueous solution, and its poly(arginine)-selective precipitation behavior was followed by monitoring the changes in luminescence. The poly(arginine)-tagged albumin precipitated selectively and quantitatively, so that the apoferritin-Tb(3+) complex can function as a new luminescent biotool for the sensing of poly(arginine) and its protein conjugates.

Photoluminescent properties of chalcobromide-capped octahedral hexarhenium(III) complexes [{Re(6)Q(8-n)Br(n)}Br(6)](n-4) (Q = Se, n = 1-3; Q = S, n = 1, 2).

Photoluminescent properties of chalcobromide-capped octahedral hexarhenium(III) complexes with terminal bromide ligands [{Re(6)Q(8-n)Br(n)}Br(6)](n-4) (Q = Se, n = 1 ([1-Se](3-)), n = 2 ([2a-Se](2-) and [2b-Se](2-)), and n = 3 ([3-Se](-)); Q = S, n = 1 ([1-S](3-)), n = 2 ([2a-S](2-), [2b-S](2-), and [2c-S](2-)) were studied. The Q(7)Br capped complex [{Re(6)Q(7)Br}Br(6)](3-) and Q(6)Br(2) [{Re(6)Q(6)Br(2)}Br(6)](2-) (both D(3d) and C(2v) symmetric geometrical isomers) were successfully separated by column chromatography. All of the chalcobromide-capped complexes studied showed photoluminescence in both crystalline and solution phases. The emission maximum wavelength of the complexes at 296 K spans 853-915 or 868-968 nm in the crystalline phase or in acetonitrile, respectively. The selenobromide-capped complexes showed more intense emission as compared with the thiobromide analogues. The emission quantum yield (Phi(em)) and emission lifetime (tau(em)) became smaller and shorter, respectively, with an increase in the number of a capping bromide ligand in [{Re(6)Q(8-n)Br(n)}Br(6)](n-4). In the crystalline phase at 80 K, the emission maximum of the chalcobromide-capped complex shifted to the longer wavelength relative to that at 296 K. The emissive excited-state of the chalcobromide-capped hexarhenium(III) complexes was concluded to originate from the {Re(6)Q(8-n)Br(n)}(n+2) core with a spin-triplet type. The Phi(em) and tau(em) values of the {Re(6)Q(8-n)Br(n)}(n+2) complex were dependent significantly on the symmetry of the hexarhenium core, showing more intense emission for the complex with the higher symmetric core. A linear correlation between natural logarithm of the nonradiative decay rate constant and the emission maximum energy was observed for [{Re(6)Q(6)Br(2)}Br(6)](2-).

Enantioselectivity-Evaluation of Chiral Copper(II) Complexes Coordinated by Novel Chiral Tetradentate Ligands for Free Amino Acids by Mass Spectrometry Coupled With the Isotopically Labeled Enantiomer Method.

A series of copper(II) complexes with chiral tetradentate ligands, N,N'-ethylene- bis(S-amino acid methyl amide or methyl ester) prepared from S-alanine, S-phenylalanine, S-valine or S-proline, was generated in methanol. The copper complexes provided three component complexes in the presence of a free chiral amino acid. The enantioselectivity for the amino acid was evaluated by electrospray ionization-mass spectrometry coupled with the deuterium-labeled enantiomer method and these copper complexes were found to exhibit high enantioselectivity for free amino acids having bulky side chains. This result suggests that steric interaction between the tetradentate ligand and free amino acid was a major factor in chiral recognition. The copper complex with a chiral tetradentate ligand prepared from S-proline showed opposite enantioselectivity to copper complexes consisting of tetradentate ligands prepared from other S-amino acids. The conformational difference of the tetradentate ligand in the copper complex was found to be significant for enantioselectivity.

Asymmetric twisting and chirality probing properties of quadruple-stranded helicates: coordination versatility and chirality response of Na(+), Ca(2+), and La(3+) complexes with octadentate cyclen ligand.

A series of Na(+), Ca(2+), and La(3+) complexes with octadentate cyclen ligand were prepared and structurally characterized in the crystal and solution states. The employed cyclen ligand formed 6-, 7-, and 9-coordinated, crystalline complexes with Na(+), Ca(2+), and La(3+) cations, respectively, in which the parent cyclen ring and quinoline-functionalized side arms were cooperatively coordinated. These three metal cations provided the quadruple-stranded helicates in CH(3)CN-C(2)H(5)OH solutions. In each helicate, four quinoline-functionalized side arms were arranged in a propeller-like fashion to yield an enantiomer-pair of Delta- and Lambda- forms. Addition of a chiral anion to the cyclen-Ca(2+) complex solution induced circular dichroism (CD) signals around the quinoline chromophore, which indicated that 1:1 diastereomeric complexation between the Ca(2+) complex and the chiral anion imposed the stereoisomeric equilibrium. The intensity and sign of the observed CD signal were significantly dependent on both the absolute configuration and the enantiomeric purity of the added anion. The corresponding cyclen-Na(+) complex rarely induced a CD signal, while the La(3+) complex exhibited complicated anion-induced spectral changes. Thus, the octadentate cyclen ligand employed was demonstrated to form the quadruple-stranded helicate with the Ca(2+) cation in the solution state, which functioned as an effective CD probe for the determination of enantiomer excess (ee%) of the chiral anions.

Cytochrome c-binding "proteo-dendrimers" as new types of apoptosis inhibitors working in HeLa cell systems.

The suppressive effects of synthetic dendrimers on mitochondrial apoptosis were first demonstrated in human epithelial carcinoma HeLa cells. The employed proteo-dendrimers included polyanionic hepta(glutamic acids), a fluorescent zinc porphyrinate core, hydrophilic polyether surface and nonpeptide hydrophobic dendrons, and electrostatically interacted with cytochrome c in aqueous solutions. The ceramide analogue, (2S,4E)-2-acetylamino-3-oxo-4-octadecen-1-ol (C2-ketoCer) induced mitochondrial apoptosis into HeLa cells and the cell viability was significantly recovered by pretreatment with some dendrimers. Among a series of proteo-dendrimers, the second-generation dendrimer 2a had the lowest cytotoxicity and the highest solubility. When the cells were treated with this dendrimer, a decrease in the protein levels of active caspase-3 and proteolytically cleaved PARP was remarkably observed. Since cytochrome c release from the mitochondria to the cytoplasm was unaffected in the presence of dendrimer 2a, the observed suppressive effects probably indicate that the proteo-dendrimer trapped cytochrome c, not only in the aqueous solutions but also in the living cells..

Transferrin-terbium complexes as luminescent pH sensing devices.

Three kinds of protein-metal complexes were developed as pH sensing devices in the aqueous solutions. Biological transferrin and lactoferrin proteins formed stable Tb3+ complexes, which exhibited long-lived and green luminescence signals. They showed pH-dependent luminescence changes around neutral pH, coupled with their Tb3+ complexation/decomplexation. Since fluorescein-labeled transferrin-Fe3+ complex exhibited fluorescence changes at lower pH, these three protein complexes covered wide pH-responsive ranges. The immobilized biotinylated transferrin-Tb3+ complexes on the micrometer-scaled bead also operated as a pH-responsive luminescent indicator. Since the transferrin ligand had rapid Tb3+ complexation/decomplexation process, its Tb3+ complex exhibited pH-responsive luminescence signals even in the presence of Fe3+ cation. A new series of tunable luminescent pH sensing devices were developed by combination of biological protein and luminescent lanthanide center.

Mass spectrometric detection of enantioselectivity in three-component complexation, copper(ii)-chiral tetradentate ligand-free amino acid in solution.

By using electrospray ionization mass spectrometry coupled with the use of deuterium-labelled quasienantiomers, enantioselective coordination of a free amino acid as the second ligand of a copper(ii) complex with a novel chiral tetradentate ligand was evaluated quantitatively in a short measurement time.

Dendrimer container for anion-responsive lanthanide complexation and "on-off" switchable near-infrared luminescence.

A new dendrimer-type ligand dynamically switched the lanthanide complexation and luminescence profiles in response to external anions.

Luminescence sensing of weakly-hydrated anions in aqueous solution by self-assembled europium(iii) complexes.

Self-assembled europium(iii) complexes produced dispersed nanoparticles with diameters of about 4-8 nm, which exhibited long-lived luminescence in a 20 wt% EtOH-H2O solution. The complexes could sense weakly hydrated anions, such as perchlorate, by a change in luminescence intensity using an anion displacement method.

Chirality sensing and size recognition of N-Boc-amino acids by cage-type dimeric lanthanide complexes: chirality detection of N-Boc-aspartate anions via luminescence colour change.

Chiral luminescent lanthanide complexes, characterized by covalently-linked face-to-face octadentate cyclen (tetraaza-12-crown-4) ligands, specifically bound a chiral N-Boc-aspartate among various N-Boc amino acid anions to enhance Eu(III) luminescence intensity at 615 nm. The combination of Tb(III) and Eu(III) complexes enabled naked-eye discrimination of N-Boc-D- and L-aspartates via the luminescence colour change.

Effects of flavonoid phytochemicals on cortisol production and on activities of steroidogenic enzymes in human adrenocortical H295R cells.

Inhibitory effects of flavonoid phytochemicals, flavones, flavonols and isoflavones on cortisol production were examined in human adrenal H295R cells stimulated with di-buthylyl cAMP. In addition, the inhibitory effects of these chemicals on the activity of P450scc, 3beta-HSD type II (3beta-HSD II), P450c17, P450c21 and P45011beta, steroidogenic enzymes involved in cortisol biosynthesis, were examined in the same cells. Exposure to 12.5 microM of the flavonoids 6-hydroxyflavone, 4'-hydroxyflavone, apigenin, daidzein, genistein and formononetin significantly decreased cortisol production (by 6.3, 69.6, 47.5, 26.6, 13.8 and 11.3%, respectively), and biochanin A significantly decreased cortisol production (by 47.3%) at a concentration of 25 microM without any significant cytotoxic effects or changes in cell number. Daidzin, the 7-glucoside of daidzein, did not alter cortisol production by H295R cells at concentrations over 10 microg/ml (24 microM). Daidzein-induced reduction of cortisol production by H295R cells was not inhibited by the estrogen receptor antagonist ICI 182,780. The flavonoids 6-hydroxyflavone, daidzein, genistein, biochanin A and formononetin strongly and significantly inhibited microsomal 3beta-HSD II activity at concentrations from 1 to 25 microM, and I(50) values were estimated to be 1.3, 2, 1, 0.5 and 2.7 microM, respectively. In addition, these flavonoids significantly inhibited microsomal P450c21 activity at 12.5 and/or 25 microM. In addition, 6-hydroxyflavone inhibited activity of microsomal P450c17 and mitochondrial P45011beta at 12.5 and/or 25 microM. Results of Lineweaver-Burk's plot analysis indicate that daidzein is a competitive inhibitor of the activity of 3beta-HSD II and P450c21. K(m) and V(max) values of 3beta-HSD II for DHEA were estimated to be 6.6 microM and 328pmol/minmg protein, respectively. K(m) and V(max) values of P450c21 for progesterone were estimated to be 2.8 microM and 16pmol/minmg protein, respectively. K(i) values of 3beta-HSD II and P450c21 for daidzein were estimated to be 2.9 and 33.3 microM, respectively.