Observation of Nonlinear Spin-Charge Conversion in the Thin Film of Nominally Centrosymmetric Dirac Semimetal SrIrO_{3} at Room Temperature.

Spin-charge conversion via spin-orbit interaction is one of the core concepts in the current spintronics research. The efficiency of the interconversion between charge and spin current is estimated based on Berry curvature of Bloch wave function in the linear-response regime. Beyond the linear regime, nonlinear spin-charge conversion in the higher-order electric field terms has recently been demonstrated in noncentrosymmetric materials with nontrivial spin texture in the momentum space. Here, we report the observation of the nonlinear charge-spin conversion in a nominally centrosymmetric oxide material SrIrO_{3} by breaking inversion symmetry at the interface. A large second-order magnetoelectric coefficient is observed at room temperature because of the antisymmetric spin-orbit interaction at the interface of Dirac semimetallic bands, which is subject to the symmetry constraint of the substrates. Our study suggests that nonlinear spin-charge conversion can be induced in many materials with strong spin-orbit interaction at the interface by breaking the local inversion symmetry to give rise to spin splitting in otherwise spin degenerate systems.

NF-kB decoy oligodeoxynucleotide preserves disc height in a rabbit anular-puncture model and reduces pain induction in a rat xenograft-radiculopathy model.

While it is known that the degenerated intervertebral disc (IVD) is one of the primary reasons for low-back pain and subsequent need for medical care, there are currently no established effective methods for direct treatment. Nuclear factor-κB (NF-κB) is a transcription factor that regulates various genes' expression, among which are inflammatory cytokines, in many tissues including the IVD. NF-κB decoy is an oligodeoxynucleotide containing the NF-κB binding site that entraps NF-κB subunits, resulting in suppression of NF-κB activity. In the present preclinical study, NF-κB decoy was injected into degenerated IVDs using the rabbit anular-puncture model. In terms of distribution, NF-κB decoy persisted in the IVDs up to at least 4 weeks after injection. The remaining amount of NF-κB decoy indicated that it fit a double-exponential-decay equation. Investigation of puncture-caused degeneration of IVDs showed that NF-κB decoy injection recovered, dose-dependently, the reduced disc height that was associated with reparative cell cloning and morphological changes, as assessed through histology. Gene expression, by quantitative real-time polymerase chain reaction (qRT-PCR), showed that NF-κB decoy attenuated inflammatory gene expression, such as that of interleukin-1 and tumor necrosis factor-α, in rabbit degenerated IVDs. NF-κB decoy also reduced the pain response as seen using the "pain sensor" nude rat xenograft-radiculopathy model. This is the first report demonstrating that NF-κB decoy suppresses the inflammatory response in degenerated IVDs and restores IVD disc height loss. Therefore, the intradiscal injection of NF-κB decoy may have the potential as an effective therapeutic strategy for discogenic pain associated with degenerated IVDs.

Search for bosonic superweakly interacting massive dark matter particles with the XMASS-I detector.

Bosonic superweakly interacting massive particles (super-WIMPs) are a candidate for warm dark matter. With the absorption of such a boson by a xenon atom, these dark matter candidates would deposit an energy equivalent to their rest mass in the detector. This is the first direct detection experiment exploring the vector super-WIMPs in the mass range between 40 and 120 keV. With the use of 165.9 day of data, no significant excess above background was observed in the fiducial mass of 41 kg. The present limit for the vector super-WIMPs excludes the possibility that such particles constitute all of dark matter. The absence of a signal also provides the most stringent direct constraint on the coupling constant of pseudoscalar super-WIMPs to electrons. The unprecedented sensitivity was achieved exploiting the low background at a level 10(-4) kg-1 keVee-1 day-1 in the detector.

Thymic stromal lymphopoietin expression is increased in the horny layer of patients with atopic dermatitis.

Thymic stromal lymphopoietin (TSLP) is known for its capacity to induce CD11c(+) myeloid dendritic cells to promote T helper type 2 (Th2)-skewed inflammatory responses. Although increased expression of TSLP was reported in the lesional skin of limited numbers of patients with atopic dermatitis (AD), the relationships between the degree of TSLP expression in the skin and the severity of AD, epidermal barrier function and eruption type remain to be elucidated. The aim of this study was to examine the relationships between the degree of TSLP expression in the skin and the severity of AD, eruption type and epidermal barrier function using a non-invasive method in a sizeable group of the patients. Stratum corneum tissue was obtained from AD patients by tape stripping, and the stratum corneum TSLP (scTSLP) expression level was evaluated using a TSLP-specific antibody followed by image analysis. The correlations between the scTSLP intensity and the severity scoring of AD (SCORAD) index and epidermal barrier function, such as stratum corneum hydration and transepidermal water loss (TEWL), were analysed. The changes in the scTSLP level induced by the application of moisturizer were also examined. The scTSLP expression level was increased in AD patients compared with healthy subjects and was correlated with SCORAD, especially with the dry skin score, and stratum corneum hydration. Moisturizer application resulted in reduced scTSLP levels. The scTSLP level can be used as a biomarker of AD severity and particularly epidermal barrier status.

Localization of a gene for Fukuyama type congenital muscular dystrophy to chromosome 9q31-33.

Fukuyama type congenital muscular dystrophy (FCMD) is an autosomal recessive severe muscular dystrophy associated with an anomaly of the brain. Twenty-one FCMD families, 13 of them with consanguineous marriages, were analysed by genetic linkage analyses with polymorphic microsatellite markers to map the FCMD gene. Significant lod scores were obtained with the markers D9S58 (Zmax = 5.81 at theta = 0.06), D9S59 (Zmax = 4.33 at theta = 0.02), and HXB (Zmax = 3.28 at theta = 0.09) on chromosome 9q31-33. Multipoint analysis placed FCMD between D9S58 and D9S59, with a maximum lod score of 16.93. These markers will be useful for presymptomatic, prenatal and carrier diagnosis of family members carrying FCMD, and they represent important resources for the identification of a gene responsible for FCMD.

Comparison of clinical outcomes of osimertinib and first-generation EGFR-tyrosine kinase inhibitors (TKIs) in TKI-untreated EGFR-mutated non-small-cell lung cancer with leptomeningeal metastases.

BACKGROUND: Leptomeningeal metastases (LM) are devastating complications of epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC). Although osimertinib, a third-generation EGFR-tyrosine kinase inhibitor (TKI), has better penetration into the central nervous system than first-generation EGFR-TKIs, data on the distinct activity of EGFR-TKIs in untreated advanced EGFR-mutated NSCLC with LM are lacking. PATIENTS AND METHODS: We retrospectively reviewed patients treated with EGFR-TKIs for TKI-untreated common EGFR-mutated NSCLC with LM between July 2002 and July 2021 at the National Cancer Center Hospital. The patients were divided into two groups: patients treated with osimertinib (Osi group) and those treated with gefitinib or erlotinib [first-generation (1G)-TKI group]. RESULTS: Of the 967 patients, 71 were eligible, including 29 in the Osi group and 42 in the 1G-TKI group. The median progression-free survival (PFS) and overall survival (OS) in the Osi group were better than those in the 1G-TKI group (PFS: 16.9 months versus 8.6 months, P = 0.007, and OS: 26.6 months versus 20.0 months, P = 0.158). The LM-overall response rate (ORR) and LM-PFS were significantly better in the Osi group than in the 1G-TKI group (LM-ORR: 62.5% versus 25.7%, P = 0.007; LM-PFS: 23.4 months versus 12.1 months, P = 0.021). In the subgroup analysis of EGFR mutation status, LM-PFS for patients with exon 19 deletion was significantly longer in the Osi group than in the 1G-TKI group (32.7 months versus 13.4 months, P = 0.013), whereas those with L858R mutation in exon 21 did not differ between the two groups. In the multivariate analysis, osimertinib and exon 19 deletion were significant factors for better LM-PFS and OS. CONCLUSION: Osimertinib can be more effective for untreated common EGFR-mutated NSCLC patients with LM, especially those with exon 19 deletion, compared to first-generation TKIs.

Increased plasma LIGHT levels in patients with atopic dermatitis.

LIGHT [the name of which is derived from 'homologous to lymphotoxins, exhibits inducible expression, competes with herpes simplex virus glycoprotein D for herpes simplex virus entry mediator (HVEM), and expressed by T lymphocytes'], is a member of the tumour necrosis factor superfamily that is involved in various inflammatory diseases. We aimed to estimate the relevance of plasma LIGHT levels as a biomarker for atopic dermatitis (AD). In order to understand the putative role of LIGHT in AD pathogenesis, we also investigate the effects of LIGHT on a monocytic cell line, human acute monocytic leukaemia cell line (THP-1). We examined plasma LIGHT levels, total serum IgE, serum value of CCL17 and peripheral blood eosinophil counts in patients with AD and healthy subjects. The effects of LIGHT on activation and apoptosis in THP-1 cells were also investigated. The plasma concentrations of LIGHT in AD patients were significantly higher than those in healthy individuals and the concentrations decreased as the symptoms were improved by treatment. The LIGHT plasma concentrations correlated with IgE levels and the Severity Scoring of AD (SCORAD) index. In addition, LIGHT stimulation increased expression of CD86 and induced production of interleukin-1ß in THP-1 cells. Apoptosis was inhibited, the Bcl-2 level increased and the caspase-3 level decreased in THP-1 cells stimulated with LIGHT, compared to unstimulated control cells. These results suggest that plasma LIGHT levels may be one of the promising biomarkers for AD.

Potential role of autoantibody in severe neutropenia of a patient with Kawasaki Syndrome.

Neutropenia associated with Kawasaki Syndrome (KS) has been rarely reported, and the detailed mechanisms responsible for this state are not yet elucidated. The aim of this study was to clarify the mechanisms of neutropenia in KS. We examined antibodies to known neutrophil antigens (HNA1a, HNA1b, HNA null, HNA2, HNA3, HNA4 and non-HLA antigen 9a) in a KS patient with neutropenia. We also performed the granulocyte immunofluorescence test (GIFT) using patient or control neutrophils incubated with the patient's serum at serial time points over the patient's clinical course. No specific antibody to known neutrophil antigens was detected. Flow cytometric analysis showed that autoantibodies bound to immature CD13-positive myeloid cells, which resulted in myeloid lineage maturation arrest in the bone marrow. GIFT showed that neutrophil-specific autoantibodies were produced by the patient, and the amount of autoantibody inversely correlated with the patient's neutrophil counts. The presence of an autoantibody to a novel antigen on immature myeloid cells or neutrophils is the likely the cause of severe neutropenia in this patient with KS.

Oral intake of γ-aminobutyric acid affects mood and activities of central nervous system during stressed condition induced by mental tasks.

γ-Aminobutyric acid (GABA) is a kind of amino acid contained in green tea leaves and other foods. Several reports have shown that GABA might affect brain protein synthesis, improve many brain functions such as memory and study capability, lower the blood pressure of spontaneously hypertensive rats, and may also have a relaxation effect in humans. However, the evidence for its mood-improving function is still not sufficient. In this study, we investigated how the oral intake of GABA influences human adults psychologically and physiologically under a condition of mental stress. Sixty-three adults (28 males, 35 females) participated in a randomized, single blind, placebo-controlled, crossover-designed study over two experiment days. Capsules containing 100 mg of GABA or dextrin as a placebo were used as test samples. The results showed that EEG activities including alpha band and beta band brain waves decreased depending on the mental stress task loads, and the condition of 30 min after GABA intake diminished this decrease compared with the placebo condition. That is to say, GABA might have alleviated the stress induced by the mental tasks. This effect also corresponded with the results of the POMS scores.

A new ABC transporter mediating the detachment of lipid-modified proteins from membranes.

Lipoproteins in Escherichia coli are anchored to the periplasmic side of either the inner or the outer membrane by a lipid moiety that is covalently attached to the amino-terminal cysteine residue. Membrane specificity depends on a sorting signal at position 2 of the lipoprotein. Lipoproteins directed to the outer membrane are released from the inner membrane in an ATP-dependent manner through the formation of a complex with LolA, a periplasmic chaperone. However, the ATPase involved in this reaction has not been identified. Here we show, using reconstituted proteoliposomes, that a new complex, LolCDE, belonging to the ATP-binding cassette (ABC) transporter family, catalyses the release of lipoproteins in LolA- and sorting-signal-dependent manners. The LolCDE complex differs mechanistically from all other ABC transporters as it is not involved in the transmembrane transport of substrates. This new mechanism is evolutionarily conserved in other gram-negative bacteria.

Lactulose ingestion causes an increase in the abundance of gut-resident bifidobacteria in Japanese women: a randomised, double-blind, placebo-controlled crossover trial.

The genus Bifidobacterium comprises various bacterial species, and the complement of species within the human intestinal tract differs from individual to individual. The balance of these bifidobacterial species remains poorly understood, although it is known that the abundance of bifidobacteria increases following the ingestion of prebiotics. We previously conducted a randomised, placebo-controlled, double-blind, crossover study of 2 g/day lactulose ingestion for 2 weeks in 60 Japanese women. To study the effect of lactulose ingestion on each bifidobacterial species, here, we measured the abundance of each of the principal bifidobacterial species. After lactulose ingestion, the log cell counts of the Bifidobacterium adolescentis group (8.97±0.08 vs 9.39±0.08, P=0.0019), Bifidobacterium catenulatum group (9.45±0.10 vs 9.65±0.10, P=0.0032) and Bifidobacterium longum group (9.01±0.07 vs 9.29±0.07, P=0.0012) were significantly higher than in the placebo ingestion control group. However, the log cell counts were similar for Bifidobacterium breve (8.12±0.12 vs 8.33±0.12, P=0.20), Bifidobacterium bifidum (9.08±0.12 vs 9.42±0.14, P=0.095) and Bifidobacterium animalis subspecies lactis (8.65±0.53 vs 8.46±0.46, P=0.77). Cluster analysis of the log cell count data at the bifidobacterial species level revealed three distinct clusters, but the combinations and ratios of the constituent bifidobacteria were not affected by lactulose ingestion. Furthermore, principal coordinate analysis of the intestinal microbiota in the lactulose and placebo ingestion groups using Illumina MiSeq showed no significant differences in the intestinal microbiota as a whole. These results suggest that 2 g/day lactulose ingestion for 2 weeks significantly increases the abundance of intestinal bifidobacteria, but does not affect the intestinal microbiota as a whole.

Expression levels of adiponectin receptors and periodontitis.

BACKGROUND AND OBJECTIVE: We recently showed that adiponectin, an adipocyte-derived cytokine, may function as a negative regulator of the Toll-like receptor signaling pathway and of osteoclast formation in periodontal disease. In this study, we investigated whether the expression levels of adiponectin receptors (AdipoR1 and AdipoR2) are related to the presence of periodontitis. MATERIAL AND METHODS: We initially examined, using RT-PCR, the expression of the AdipoR1 and AdipoR2 genes at the mRNA level in several oral tissues of C57BL mice. Next, we investigated (using real-time PCR assays) whether inflammatory cytokines, such as tumor necrosis factor-alpha, could affect the expression levels of these genes in human gingival fibroblasts. Lastly, we compared the expression levels of these receptor proteins in gingival tissues between two healthy subjects and five patients with severe periodontal disease using western blotting analysis. RESULTS: The AdipoR1 and AdipoR2 receptors were ubiquitously expressed in the oral tissues of mice. We observed that treatment with tumor necrosis factor-alpha could significantly reduce the expression levels of both AdipoR1 and AdipoR2 genes in human gingival fibroblasts. Moreover, we found that the expression of both receptors was lower in periodontal tissues from patients with severe periodontitis than in patients with healthy periodontal tissues. CONCLUSION: These observations suggest that adiponectin may not function efficiently in sites of periodontal disease because of a decrease in the number of its receptors, and this probable dysfunction may play a role in worsening periodontitis in patients.

Metal ion and vitamin adsorption profiles of phosphate binder ion-exchange resins.

AIMS: To determine the metal ion and vitamin in vitro adsorption profile of sevelamer hydrochloride (sevelamer-HCl) and colestilan(INN)/colestimide(JAN), a novel ion-exchange resin being developed as a phosphate binder for end-stage renal disease (ESRD) patients undergoing hemodialysis, adsorption of metal ions (iron, cobalt, copper and zinc) and vitamins (B6, B12, C, K and folic acid) essential for hematopoiesis/blood coagulation was assessed. METHODS: Mixtures of each resin (colestilan or sevelamer-HCl, 4 mg/ml) and metal ions (Fe(III), Fe(II), Co(II), Cu(II), and Zn(II), 1 microg/ml) were adjusted to pH 1.2 or 6.8 and incubated at 37 degrees C for 1 hour. Metal ions in the recovered filtrate were detected by inductively coupled plasma optical emission spectrometry. In addition, the mixtures of each resin (4 mg/ml) and vitamins (B6, B12, C, K and folic acid, 0.5 - 250 microg/ml) were adjusted to pH 6.8 and incubated at 37 degrees C for 0.5 hour. The vitamin concentrations in the recovered filtrate were quantified by HPLC. RESULTS: Colestilan did not adsorb any metals tested at either pH level, whereas sevelamer-HCl adsorbed copper(II) and zinc(II) ion at pH 6.8 with adsorption ratios of 99% and 38%, respectively. Both resins showed almost complete adsorption of vitamin C, vitamin K, and folic acid, but weak adsorption of vitamin B6, and no adsorption of vitamin B12. CONCLUSIONS: The differing adsorption profiles for metal ions and vitamins between sevelamer-HCl and colestilan may be of importance for the individualized management of anemia and malnutrition in chronic hemodialysis patients receiving phosphate binding ion-exchange resins for the control of hyperphosphatemia.

A novel orexin antagonist from a natural plant was discovered using zebrafish behavioural analysis.

OBJECTIVE: Phenotypic screening is one of the most practical approaches to the identification of mediators of behaviour, since it is difficult to model brain function in vitro, at a cellular level. We used a zebrafish (Danio rerio) behavioural assay to discover novel, natural, neuroactive compounds. MATERIALS AND METHODS: A zebrafish behavioural assay was performed for seven natural compounds, obtained from plants. The behavioural profiles were compared to those of known psychoactive drugs. We characterised a natural compound exhibiting a behaviour profile similar to that of suvorexant, using in silico, in vitro and microarray expression analysis. RESULTS: The behavioural analysis performed in this study classified central nervous system drugs according to their mechanism. Zebrafish treated with a natural compound, 8b-(4'-Hydroxytigloyloxy) costunolide (8b), showed behaviour profiles similar to those of zebrafish treated with suvorexant, a known orexin antagonist. This behavioural assay was validated using in silico and in vitro assays, which revealed that the new compound was a dual orexin receptor antagonist. In addition, transcriptome analysis suggested that 8b might regulate the nuclear factor-κB (NF-κB) related pathway. CONCLUSIONS: We conclude that zebrafish phenotypic screening, combined with in silico assays and gene expression profiling, is a useful strategy to discover and characterize novel therapeutic compounds, including natural products.

Association analysis between canine behavioural traits and genetic polymorphisms in the Shiba Inu breed.

The relationships between behavioural trait data and the genotype of 15 polymorphisms in eight neurotransmitter-related genes were analysed in 77 dogs of the Shiba Inu breed, an indigenous Japanese dog. The data were obtained from a 26-item questionnaire on the dog's behaviour, distributed to the dog's owners, through veterinary hospitals and the Shiba Inu breed magazine. A factor analysis of the questionnaire items extracted eight factors accounting for 66.8% of the variance. An association analysis between these factors and genetic polymorphisms indicated that the polymorphism of c.471T>C in the solute carrier family 1 (neuronal/epithelial high-affinity glutamate transporter) member 2 (SLC1A2) gene was significantly associated with Factor 1, referred to as 'aggression to strangers'. This association remained stable in separate analyses of data from surveys obtained from the hospitals and those obtained from the magazine. The results suggest that the c.471T>C polymorphism is associated with some types of aggressive behaviour in the Shiba Inu. Further studies using other dog breeds are necessary to extend these findings to dogs in general.

Effect of intensive interval training during unloading on muscle deoxygenation kinetics.

The present study investigated the effects of intensive interval training during 20-day of unloading on local muscle oxygenation kinetics evaluated by near infrared spectroscopy technique (NIRS). Eleven adult men completed 20-day unloading and were divided into two groups; the control (CON) group and training (TR) group. The TR group engaged in exercise training sessions that consisted of one-legged submaximal cycle exercise using the unloaded leg at 60 approximately 80% of VO(2peak) with intermittent rest periods, 25 min/day every other day. All subjects performed isometric knee extension exercise at 50% of their maximum voluntary contraction force before and after unloading. NIRS Delta[deoxy-Hb/Mb] signal was recorded from m. vastus lateralis and was fitted to an exponential equation in order to determine the kinetics parameters. The time constant (tau) of the % Delta[deoxy-Hb/Mb] was unchanged in the TR group, while it significantly increased in the CON group after unloading (pre, 5.0+/-1.0; post, 7.4+/-1.0 s). It is concluded that 20-day unloading increased the tau, suggesting deterioration of capacity for oxidative phosphorylation and oxygen utilization in a skeletal muscle. Additionally, the preservation of tau in the TR group suggested that intensive interval training could have an impact on the maintenance of muscle oxidative metabolism during unloading.

Prebiotic effect of two grams of lactulose in healthy Japanese women: a randomised, double-blind, placebo-controlled crossover trial.

Sixty healthy Japanese women with a defaecation frequency of 2-4 times/week participated in this randomised, double-blind crossover trial. Participants received 2 g/day lactulose for 2 weeks and placebo in a random order, separated by a washout period of 3 weeks. Eight participants were excluded who did not satisfy the conditions, and therefore data from 52 were analysed. The primary outcome was defaecation frequency and the secondary outcomes were the number of defaecation days, faecal consistency, faecal volume, and the number and percentage of Bifidobacterium in faeces. The defaecation frequency (times/week) was significantly higher during lactulose (4.28±0.23) than placebo (3.83±0.23) treatment (delta (Δ) 0.45 [95% confidence interval (CI) 0.10-0.80], P=0.013). The defaecation days (days/week) was significantly higher during lactulose (3.77±0.17) than placebo (3.47±0.17) treatment (Δ0.30 [95% CI 0.04-0.56], P=0.024). Faecal consistency using the Bristol Stool Scale (/defaecation) was significantly higher during lactulose (3.84±0.10) than placebo (3.68±0.10) treatment (Δ0.16 [95% CI 0.00-0.31], P=0.044). Faecal volume (/week) was significantly higher during lactulose (21.73±3.07) than placebo (17.65±3.07) treatment (Δ4.08 [95% CI 0.57-7.60], P=0.024). The number of Bifidobacterium in faeces (log colony forming units/g faeces) was significantly higher during lactulose (9.53±0.06) than placebo (9.16±0.06) treatment (Δ0.37 [95% CI 0.23-0.49], P<0.0001). The percentage of Bifidobacterium in faeces was also significantly higher during lactulose (25.3±1.4) than placebo (18.2±1.4) treatment (Δ7.1 [95% CI 2.9-11.4], P=0.0014). Finally, straining at defaecation (/defaecation) during lactulose (3.62±0.24) treatment was significantly lower than during placebo (3.97±0.24) treatment (Δ0.35 [95% CI -0.69 - -0.02], P=0.037). No significant difference was observed between lactulose and placebo with regard to flatulence. Severe adverse effects did not occur. Thus, oral ingestion of 2 g/day lactulose had a prebiotic effect, increasing the number and percentage of bifidobacteria in faeces, softening the faeces, and increasing defaecation frequency, but without increasing flatulence.

Screening of Nepalese crude drugs traditionally used to treat hyperpigmentation: in vitro tyrosinase inhibition.

South-East Asian population is daily exposed to strong sunlight. As a result, the majority of population will have darker, ethnic skin. Moreover, many people suffer from dark spots, hyperpigmentation, which is considered to be a skin disorder and causes psychological disturbance. To treat dark spots, most of the population will still rely on traditionally used crude drugs, knowledge about which is transferred from generation to generation. Fifty-two crude drugs were selected based on the survey performed among local healers and beauticians of different ethnic origin. These crude drugs were screened for mushroom tyrosinase inhibitory activity, as tyrosinase inhibitors are becoming increasingly important as cosmetic and medicinal products, primarily to control hyperpigmentation. Among the tested crude drugs, methanolic extracts of Glycyrrhiza glabra, Morus alba, Syzygium aromaticum, Citrus aurantifolia, Cypreae moneta, Punica granatum and Citrus aurantium, at the final concentration of 50 microg mL(-1), showed mushroom tyrosinase inhibitory activity of 78.9%, 71.0%, 69.4%, 59.0%, 56.0%, 53.4 and 51.9%, respectively, with 91.4% inhibitory activity of kojic acid taken as positive control. To our knowledge, this is the first report that extracts of Cypreae moneta shell and Syzygium aromaticum flowering bud have tyrosinase inhibitory activity. These potent extracts were further evaluated at different concentration. The final concentration of the extracts in reaction mixtures was 50, 25 and 5 microg mL(-1) for the initial concentration of 1000, 500 and 100 microg mL(-1), respectively. They showed concentration-dependent inhibition of mushroom tyrosinase. Those extracts expressing relatively weak tyrosinase inhibitory activity may act through different inhibition pathway which is not based on tyrosinase activity. Further evaluation of the most potent tyrosinase inhibitors in in vivo conditions would be recommended.