Practical synthesis of kainoids: a new chemical probe precursor and a fluorescent probe.

A practical total synthesis of kainoid MFPA (5) was achieved in only six steps, via a novel Ni-catalyst-mediated asymmetric conjugate addition reaction. Furthermore, a fluorescein-based fluorescent ionotropic glutamate receptor probe 28 was efficiently synthesized from a precursor derived from a synthetic intermediate of 5.

A pragmatic dose-finding approach using short-term surrogate efficacy outcomes to evaluate binary efficacy and toxicity outcomes in phase I cancer clinical trials.

There is a growing need for study designs that can evaluate efficacy and toxicity outcomes simultaneously in phase I or phase I/II cancer clinical trials. Many dose-finding approaches have been proposed; however, most of these approaches assume binary efficacy and toxicity outcomes, such as dose-limiting toxicity (DLT), and objective responses. DLTs are often defined for short time periods.

Chaihu-Shugan-San administration ameliorates perimenopausal anxiety and depression in rats.

Chaihu-Shugan-San (CSS) is a traditional Chinese herbal formula that is widely used for treating perimenopausal symptoms in China; however, its mechanisms remain unknown. The present study was designed to investigate potential CSS mechanisms in rats with unpredicted chronic mild stress (UCMS) and normally aging rats (52 weeks of age). We performed the sucrose consumption test along with the forced swimming test to confirm depression-like behavior and the open field test (OFT) to confirm anxiety-like behavior in the animals.

Regional circadian period difference in the suprachiasmatic nucleus of the mammalian circadian center.

The suprachiasmatic nucleus (SCN) is the mammalian circadian rhythm center. Individual oscillating neurons have different endogenous circadian periods, but they are usually synchronized by an intercellular coupling mechanism. The differences in the period of each oscillating neuron have been extensively studied; however, the clustering of oscillators with similar periods has not been reported.

Physicochemical and biopharmaceutical characterization of amorphous solid dispersion of nobiletin, a citrus polymethoxylated flavone, with improved hepatoprotective effects.

The present study aimed to develop an amorphous solid dispersion (SD) of nobiletin (NOB), a citrus polymethoxylated flavone, with the aim of improving its biopharmaceutical and hepatoprotective properties. SD formulation of NOB (NOB/SD) was prepared by wet-milling and subsequent freeze drying, and its stability and dissolution properties were characterized. The hepatoprotective effects and pharmacokinetic behavior of orally dosed NOB/SD were evaluated in rats.

Efficacy of N-terminal pro-brain natriuretic peptide digit number for screening of cardiac disease in new haemodialysis patients.

Aim: The usefulness of the absolute N-terminal pro-brain natriuretic peptide (NT-ProBNP) concentration and its digit number for screening for cardiac disease was explored in new haemodialysis patients.

Methods: A cross-sectional study involving 71 (68 ± 14 years, 83% male) new dialysis patients was conducted. Receiver operator characteristic curve analysis was performed to identify the cutoff level of NT-proBNP for identifying cardiac disease at the start of dialysis.

Chemoselective hydrogenation reaction of unsaturated bonds in the presence of an o-nitrobenzenesulfonyl group.

Chemoselective hydrogenation of unsaturated compounds bearing an o-nitrobenzenesulfonyl (Ns)-amide moiety, affording the corresponding saturated compounds, was accomplished efficiently without loss of the nitro group by using the Pd/MS3A catalyst and a H2 balloon. Partial hydrogenation of alkynes bearing an Ns group to corresponding cis alkenes was achieved with the combination of the Pd/BN catalyst and an additive (diethylenetriamine or acetic acid).

Chemical synthesis of tea polyphenols and related compounds.

Tea polyphenol "catechin", which is a major constituent of green tea extract, has received special attention for its important bioactivities. In this article, we review the recent various syntheses of catechins by classifying the mode of of flavan ring-construction. Additionally, we also take notice of the application of the modified catechins that were created to uncover the mechanism of bioactivities and discover new activities.

Behavioral performance at early (4 weeks) and later (6 months) stages in rats with unilateral medial forebrain bundle and striatal 6-hydroxydopamine lesions.

Our previous studies showed differences in striatal D(2) receptor functional activity between two different rat parkinsonian models, with lesions induced by 6-hydroxydopamine injection in the striatum and in the medial forebrain bundle (MFB) at both early (4 weeks) and later (6 months) stages after lesioning. The present study compared behavioral changes, including rotational movements induced by methamphetamine and bromocriptine, and the stepping test, in both models at both stages. No differences in behavioral performance were observed between the early and later stages in both striatal and MFB lesion models, whereas simultaneous D(2) receptor study showed dynamic change in D(2) receptors in MFB lesion rats.

Generation of fluorocarbon and hydrocarbon hybrid gemini surfactants controlled by micellar miscibility.

Hybrid surfactants were generated through the simple mixing of fluorocarbon and hydrocarbon gemini surfactants in aqueous solutions at 25°C. Disulfide exchange between the disulfide in the spacer chain occurred in the mixed micelles. However, the generation of hybrid gemini surfactants was particularly inhibited by the addition of salt.

Effect of subthalamic nucleus stimulation during exercise on the mesolimbocortical dopaminergic region in Parkinson's disease: a positron emission tomography study.

To elucidate the dynamic effects of deep brain stimulation (DBS) in the subthalamic nucleus (STN) during activity on the dopaminergic system, 12 PD patients who had STN-DBS operations at least 1 month prior, underwent two positron emission tomography scans during right-foot movement in DBS-off and DBS-on conditions. To quantify motor performance changes, the motion speed and mobility angle of the foot at the ankle were measured twice. Estimations of the binding potential of [(11)C]raclopride (BP(ND)) were based on the Logan plot method.

Effects of ghrelin on the intracellular calcium concentration in rat aorta vascular smooth muscle cells.

Background/aims: Ghrelin has been regarded as a cardioprotective factor with complicated mechanisms. Whether ghrelin is vasodilative or vasoconstrictive in nature is controversial, and the effects of ghrelin on intracellular calcium concentration are still unclear. To explore the mechanisms involved in the vasoactive regulation of ghrelin at the cellular level, we investigated the effects of ghrelin on calcium concentrations in rat aorta vascular smooth muscle cells (VSMCs).

Catalytic desymmetrization of cyclohexadienes by asymmetric bromolactonization.

Asymmetric bromolactonization of prochiral cyclohexadiene derivatives with N-bromosuccimide proceeded in the presence of (DHQD)(2)PHAL as a chiral catalyst to afford the corresponding bromolactones with up to 93% ee. This reaction was also applicable to the kinetic resolution of a racemic cyclic ene-carboxylic acid, where the starting material was recovered with high enantioselectivity.

Peripheral stimulation in treating Parkinson's disease: Is it a realistic idea or a romantic whimsicality?

Parkinson's disease (PD) is a common, however, intractable neurodegenerative disorder in the aging population. Levodopa (l-dopa) administration is regarded as the most effective strategy in treating PD with prominent motor side-effects after undergoing long-term treatment. Surgical therapies such as deep brain stimulation (DBS) show certain efficacy, yet there are several limitations in adopting such surgical procedures.

Efficacy of multidrug superselective intra-arterial chemotherapy (docetaxel, cisplatin, and 5-fluorouracil) using the Seldinger technique for tongue cancer.

Conclusion: This therapy produced better results than intravenous multidrug chemotherapy (CF therapy, CPF therapy, etc.) or superselective intra-arterial chemotherapy (SIC) alone with cisplatin (CDDP) and 5-fluorouracil (5-FU). Primary tumor may be controlled by SIC alone in cases of T2 and many cases of T3 tumors, and by the combination of SIC and concurrent radiotherapy in cases of T3 and many cases of T4a.

The food reaching test: a sensitive test of behavioral improvements by deep brain stimulation in MPTP-treated monkey.

We modified an objective behavioral test, namely the food reaching test (FRT), for quantitative assessment of motor performance improved by deep brain stimulation (DBS) of the subthalamic nucleus (STN) in the Parkinsonian monkeys. The symptomatic features and their severity in 3 monkeys treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) were evaluated with a subjective monkey Parkinson's disease rating scale (PDRS). We then performed STN-DBS with the minimum current intensity that stopped the tremor.

Differential effects of TGF-β1 and FGF-2 on SDF-1α expression in human periodontal ligament cells derived from deciduous teeth in vitro.

Stromal cell-derived factor (SDF)-1α has been reported to play a crucial role in stem cell homing and recruitment to injured sites. However, no information is available about its role in periodontal tissues. The aim of this in vitro study was to investigate the effects of basic fibroblast growth factor (FGF-2) and transforming growth factor (TGF)-β1 on SDF-1α expression in immortalized periodontal ligament (PDL) cells derived from deciduous teeth (SH9 cells).

A mutation at IVS1 + 5 of the von Hippel-Lindau gene resulting in intron retention in transcripts is not pathogenic in a patient with a tongue cancer?: case report.

Background: Von Hippel-Lindau disease (VHL) is a dominantly inherited familial cancer syndrome predisposing the patient to a variety of malignant and benign neoplasms, most frequently hemangioblastoma, renal cell carcinoma, pheochromocytoma, and pancreatic tumors. VHL is caused by mutations of the VHL tumor suppressor gene on the short arm of chromosome 3, and clinical manifestations develop if both alleles are inactivated according to the two-hit hypothesis. VHL mutations are more frequent in the coding region and occur occasionally in the splicing region of the gene.

3,3',4',5,5'-Pentahydroxyflavone is a potent inhibitor of amyloid β fibril formation.

The natural flavonoid fisetin (3,3',4',7-tetrahydroxyflavone) is neurotrophic and prevents fibril formation of amyloid β protein (Aβ). It is a promising lead compound for the development of therapeutic drugs for Alzheimer's disease. To find even more effective drugs based on the structure of fisetin, we synthesized a series of fisetin analogues lacking the 7-hydroxyl group and compared their effects on Aβ fibril formation determined by the thioflavin T fluorescence assay.

Fibroblast growth factor 2 inhibits the expression of stromal cell-derived factor 1α in periodontal ligament cells derived from human permanent teeth in vitro.

Although cells derived from periodontal ligament (PDL) tissue are reported to have stem cell-like activity and are speculated to play a crucial role for tissue healing and regeneration after injury or orthodontic treatment, mechanisms regulating their recruitment and activation remain unknown. Recently, stromal cell-derived factor 1α (SDF-1α) has been reported to be important for stem cell homing and recruitment to injured sites. The aim of this study was to evaluate whether fibroblast growth factor 2 (FGF-2) affects the expression of SDF-1α in PDL cells derived from human permanent teeth in vitro.

The herbal medicine Inchinko-to reduces hepatic fibrosis in cholestatic rats.

Purpose: Several studies have reported the herbal medicine Inchinko-to (ICKT) to have an antifibrotic effect which thus leads to an improvement of hepatic injury. However, there are still few reports of its use in the treatment of cholestatic liver disorder. The aim of this study was to clarify whether the administration of ICKT will ameliorate hepatic fibrosis and injury in cholestatic rats.

Furan fatty acid as an anti-inflammatory component from the green-lipped mussel Perna canaliculus.

A lipid extract of Perna canaliculus (New Zealand green-lipped mussel) has reportedly displayed anti-inflammatory effects in animal models and in human controlled studies. However, the anti-inflammatory lipid components have not been investigated in detail due to the instability of the lipid extract, which has made the identification of the distinct active components a formidable task. Considering the instability of the active component, we carefully fractionated a lipid extract of Perna canaliculus (Lyprinol) and detected furan fatty acids (F-acids).

Aqueous solution properties of disulfide-linked fluorinated gemini and cleaved monomeric thiol surfactants.

We prepared a fluorinated gemini surfactant containing a disulfide bond in its spacer chain, [C₈F₁₇(CH₂)₃N(CH₃)₂CH₂CH₂SSCH₂CH₂N(CH₃)₂(CH₂)₃C₈F₁₇]2Cl, and its analogue with a hexamethylene spacer. Monomeric thiol surfactant, [C₈F₁₇(CH₂)₃N(CH₃)₂CH₂CH₂SH]Cl, was readily produced by the cleavage of the gemini surfactant using dithiothreitol in water. The critical micelle concentration was determined using surface tension, conductivity, and fluorescence probe methods.