Effect of the probiotic Weissella cibaria CMS1 on the immune response and the oral microbiome: a randomized, double-blind, placebo-controlled, parallel study.

The oral cavity connects the external environment and the respiratory and digestive systems, and the oral microbial ecosystem is complex and plays a crucial role in overall health and immune defense against external threats. Recently, the potential use of probiotics for disease prevention and treatment has gained attention. This study aimed to assess the effect of Weissella cibaria CMS1 (W. cibaria CMS1) consumption on the oral microbiome and immune function in healthy individuals through a 12-week clinical trial. This randomized, double-blind, placebo-controlled, parallel trial enrolled 90 healthy subjects. The consumption of W. cibaria CMS1 significantly increased salivary immunoglobulin A (p = 0.046) and decreased tumor necrosis factor-α (TNF-α) levels (p = 0.008). Analysis of the oral microbiota revealed changes in beta diversity, increased abundance of Firmicutes and Actinobacteria, and decreased abundance of Bacteroidetes and Fusobacteria after 12 weeks of consuming W. cibaria CMS1. Significant increases in various strains, including Lactobacillales, Bacilli, Streptococcaceae, Streptococcus, and Firmicutes, were observed in the W. cibaria CMS1 group after 12 weeks of intake. Additionally, Fusobacteriia Fusobacteriales Fusobacteriaceae and Fusobacteriia Fusobacteriales Fusobacteriaceae Fusobacterium exhibited a positive correlation with TNF-α. These findings demonstrate the positive effect of W. cibaria CMS1 on the oral environment and immune function.

Protective effect of gomisin N on benzyl butyl phthalate-induced dysfunction of testosterone production in TM3 Leydig cells.

BACKGROUND: Exposure to benzyl butyl phthalate (BBP) may induce disorders in the male reproductive system. However, the molecular mechanisms remain unknown. Here we investigated the effect of BBP on testosterone production and its molecular mechanisms. Furthermore, we also investigated the role of gomisin N (GN) from Schisandra chinensis (S. chinensis) in testosterone synthesis in TM3 Leydig cells. METHOD AND RESULTS: First, we examined the effects of BBP on expression levels of testosterone biosynthesis-related genes (StAR, CYP11α1, CYP17α1, 3ßHSD, and 17ßHSD) and attenuation-related genes (CYP1ß1, CYP19α1, and Srd5α1-3). Although testosterone biosynthesis-related genes did not change, attenuation-related genes such as CYP1ß1 and CYP19α1 were upregulated with ROS generation and testosterone level attenuation in the presence of 50 µM of BBP. However, the compound with the highest ROS and ONOO- scavenging activity from S. chinensis, GN, significantly reversed the expression of BBP-induced testosterone attenuation-related gene to normal levels. Subsequently, GN improved the testosterone production levels in TM3 Leydig cells. These events may be regulated by the antioxidant effect of GN. CONCLUSIONS: On conclusion, our study suggests, for the first time, that BBP impairs testosterone synthesis by the modulation of CYP1ß1 and CYP19α1 expression in TM3 cells; GN could potentially minimize the BBP-induced dysfunction of TM3 cells to produce testosterone by suppressing CYP19α1 expression.

Brown Seaweed Consumption as a Promising Strategy for Blood Glucose Management: A Comprehensive Meta-Analysis.

Diabetes is a chronic condition that can lead to various complications; therefore, there is a need to emphasize prevention and management. Dietary interventions, such as the Mediterranean diet or calorie-restricted regimens, coupled with exercise-induced weight reduction, have been recommended for enhancing diabetes management. Seaweeds contain various functional components, such as polyphenols and fucoidan, which have been reported to exert multiple benefits, including blood glucose regulation, improved intestinal health, and enhanced of lipid profiles. The association between blood glucose and seaweed consumption has been established in previous research. We searched the PubMed, RISS, Google Scholar, ScienceDirect, and Cochrane Library databases to identify relevant studies after applying the selection/exclusion criteria, and 23 studies were ultimately included in this analysis. Comprehensive Meta-Analysis (CMA) software version 4.0 was used to assess statistical significance and heterogeneity. In this meta-analysis, postprandial blood glucose, glycated hemoglobin (HbA1c), and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) levels demonstrated significant improvements in the seaweed group compared to the control group. Conversely, fasting blood glucose and insulin levels did not show significant associations with seaweed consumption. Subgroup analysis revealed that a high dose (1000 mg or more) was more beneficial than a low dose, and seaweeds such as Laminaria digitata, Undaria pinnatifida, Acophyllum nodosum, and Fucus vesiculosus were found to be more effective at improving blood glucose levels than control treatments. Therefore, based on our research, seaweed supplementation appears to be a promising strategy for reducing postprandial blood glucose, HbA1c, and HOMA-IR levels, thereby enabling better blood glucose management and leading to a decreased risk of type 2 diabetes.

A Meta-Analysis of the Effects of Comprehensive Sexuality Education Programs on Children and Adolescents.

Childhood and adolescence are crucial periods for developing one's awareness of sexuality. Comprehensive Sexuality Education (CSE) during these stages is essential for overall growth, fostering healthy self-concepts, and addressing diverse sexual issues among children and adolescents globally. A meta-analysis was conducted to analyze the effectiveness of CSE programs. A literature search was performed on EMBASE, PubMed, CINAHL, Cochrane Library, and PsycInfo for studies published before 14 June 2023, and based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We used the Comprehensive Meta-Analysis (CMA, V4) software version 4.0 for the analysis and interpreted the effect sizes according to Cohen's definition. Between 2011 and 2020, 21 studies on CSE were published, with the United States having the most publications (17). Of the 34 studies reviewed, 20 were randomized controlled trials. The primary population for CSE was middle/high school students (15), with the most frequent age range being 10-19 years (26). The overall effect size of CSE was significant (effect size = 1.31, p < 0.001), with cognition (effect size = 5.76, p < 0.001) being the most significant. CSE is an effective educational tool for children and adolescents with a significant impact on variables such as cognition and abstinence. It should be incremental from childhood and adolescence to adulthood.

Rice Bran Extract Suppresses High-Fat Diet-Induced Hyperlipidemia and Hepatosteatosis through Targeting AMPK and STAT3 Signaling.

Rice bran, a by-product of rice milling, is abundant in bioactive molecules and is highly recognized for its health-promoting properties, particularly in improving metabolic conditions. Building on this knowledge, we aimed to optimize the extraction conditions to maximize the functional efficacy of rice bran extract (RBE) and further validate its impact on lipid metabolism. We found that the optimized RBE (ORBE) significantly suppressed high-fat diet-induced weight gain, hyperlipidemia, and hepatosteatosis in mouse models. ORBE treatment not only suppressed lipid uptake in vivo, but also reduced lipid accumulation in HepG2 cells. Importantly, we discovered that ORBE administration resulted in activation of AMPK and inhibition of STAT3, which are both crucial players in lipid metabolism in the liver. Collectively, ORBE potentially offers promise as a dietary intervention strategy against hyperlipidemia and hepatosteatosis. This study underlines the value of optimized extraction conditions in enhancing the functional efficacy of rice bran.

Structural analysis and prebiotic activity of exopolysaccharide produced by probiotic strain Bifidobacterium bifidum EPS DA-LAIM.

Exopolysaccharide (EPS)-producing Bifidobacterium bifidum EPS DA-LAIM was isolated from healthy human feces, the structure of purified EPS from the strain was analyzed, and its prebiotic activity was evaluated. The EPS from B. bifidum EPS DA-LAIM is a glucomannan-type heteropolysaccharide with a molecular weight of 407-1007 kDa, and its structure comprises 2-mannosyl, 6-mannosyl, and 2,6-mannosyl residues. The purified EPS promoted the growth of representative lactic acid bacteria and bifidobacterial strains. Bifidobacterium bifidum EPS DA-LAIM increased nitric oxide production in RAW 264.7 macrophage cells, indicating its immunostimulatory activity. Bifidobacterium bifidum EPS DA-LAIM also exhibited high gastrointestinal tract tolerance, gut adhesion ability, and antioxidant activity. These results suggest that EPS from B. bifidum EPS DA-LAIM is a potentially useful prebiotic material, and B. bifidum EPS DA-LAIM could be applied as a probiotic candidate. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-022-01213-w.

Schisandrol A and gomisin N from Schisandra chinensis extract improve hypogonadism via anti-oxidative stress in TM3 Leydig cells.

BACKGROUND/OBJECTIVES: Male hypogonadism is a condition where the body does not produce enough testosterone and significantly impacts health. Age, obesity, genetics, and oxidative stress are some physiological factors that may contribute to testosterone deficiency. Previous studies have shown many pharmacological benefits of Schisandra chinensis (S. chinensis) Baillon as an anti-inflammatory and antioxidant. However, the molecular mechanism of attenuating hypogonadism is yet to be well established. This research was undertaken to study the effects of S. chinensis extract (SCE) on testosterone deficiency. MATERIALS/METHODS: S. chinensis fruit was pulverized and extracted using 60% aqueous ethanol. HPLC analysis was performed to analyze and quantify the lignans of the SCE. RESULTS: The 2,2-diphenyl-2-picrylhydrazyl and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) scavenging assays confirmed that the SCE and its major lignans (schisandrol A and gomisin N) inhibit oxidative stress. Effects of SCE analysis on the testosterone level under oxidative stress conditions revealed that both schisandrol A and gomisin N were able to recover the lowered testosterone levels. Through mRNA expression of TM3 Leydig cell, we observed that the SCE lignans were able to induce the enzymes involved in testosterone biosynthesis-related genes such as 3ß-HSD4 (P < 0.01 for SCE, and P < 0.001 for schisandrol A and gomisin N), 17ß-HSD3 (P < 0.001 for SCE, schisandrol A and gomisin N), and 17, 20-desmolase (P < 0.01 for schisandrol A, and P < 0.001 for SCE and gomisin N). CONCLUSIONS: These results support that SCE and its active components could be potential therapeutic agents for regulating and increasing testosterone production.

The complete chloroplast genome of Porella gracillima Mitt. (Porellaceae) and phylogenetic relationships to other bryophytes.

Porella gracillima Mitt. (Jungermanniidae, Porellaceae), a bryophyte is widespread in temperate Asia and North America. In Korea, P. gracillima is mainly observed in shaded and dried rocks or tree trunks on mountains. Here, we determined the complete chloroplast (cp) genome sequence of P. gracillima to provide useful genetic information in the phylogenetic relationship, phylogeographic history, and conservation of the species. The complete cp genome of P. gracillima was assembled using NGS Illumina HiSeqX platform. The cp genome was 121,867 bp in length (GC contents, 33.7%) and showed a typical quadripartite structure, consisting of a large single copy (LSC) of 83,406 bp, a small single copy (SSC) of 19,692 bp, and two inverted repeats (IRs) of 9,385 bp. Phylogenetic analysis shows that Porellaceae was a sister group of Radulaceae, which agrees with the findings of the previous phylogenetic studies. Our cp genome data of P. gracillima may contribute to a better understanding of the evolution of the Porella in Porellaceae and will help to infer its molecular identification, thereby providing a guideline for conservation.

Potential Probiotic Properties of Exopolysaccharide-Producing Lacticaseibacillus paracasei EPS DA-BACS and Prebiotic Activity of Its Exopolysaccharide.

Exopolysaccharide (EPS)-producing Lacticaseibacillus paracasei EPS DA-BACS was isolated from healthy human feces and its probiotic properties, as well as the structure and prebiotic activity of the EPS from this strain were examined. EPS from L. paracasei EPS DA-BACS had a ropy phenotype, which is known to have potential health benefits and is identified as loosely cell-bounded glucomannan-type EPS with a molecular size of 3.7 × 106 Da. EPS promoted the acid tolerance of L. paracasei EPS DA-BACS and provided cells with tolerance to gastrointestinal stress. The purified EPS showed growth inhibitory activity against Clostridium difficile. L. paracasei EPS DA-BACS cells completely inhibited the growth of Bacillus subtilis, Pseudomonas aeruginosa, and Aspergillus brasiliensis, as well as showed high growth inhibitory activity against Staphylococcus aureus and Escherichia coli. Treatment of lipopolysaccharide-stimulated RAW 264.7 cells with heat-killed L. paracasei EPS DA-BACS cells led to a decrease in the production of nitric oxide, indicating the anti-inflammatory activity of L. paracasei EPS DA-BACS. Purified EPS promoted the growth of Lactobacillus gasseri, Bifidobacterium bifidum, B. animalis, and B. faecale which showed high prebiotic activity. L. paracasei EPS DA-BACS harbors no antibiotic resistance genes or virulence factors. Therefore, L. paracasei EPS DA-BACS exhibits anti-inflammatory and antimicrobial activities with high gut adhesion ability and gastrointestinal tolerance and can be used as a potential probiotic.

Nanophotosensitizers Composed of Phenyl Boronic Acid Pinacol Ester-Conjugated Chitosan Oligosaccharide via Thioketal Linker for Reactive Oxygen Species-Sensitive Delivery of Chlorin e6 against Oral Cancer Cells.

Chlorin E6 (Ce6)-incorporated nanophotosensitizers were fabricated for application in photodynamic therapy (PDT) of oral cancer cells. For this purpose, chitosan oligosaccharide (COS) was conjugated with hydrophobic and reactive oxygen species (ROS)-sensitive moieties, such as phenyl boronic acid pinacol ester (PBAP) via a thioketal linker (COSthPBAP). ThdCOOH was conjugated with PBAP to produce ThdCOOH-PBAP conjugates and then attached to amine groups of COS to produce a COSthPBAP copolymer. Ce6-incorporated nanophotosensitizers using the COSthPBAP copolymer were fabricated through the nanoprecipitation and dialysis methods. The Ce6-incorporated COSthPBAP nanophotosensitizers had a small diameter of less than 200 nm with a mono-modal distribution pattern. However, it became a multimodal and/or irregular distribution pattern when H2O2 was added. In a morphological observation using TEM, the nanophotosensitizers were disintegrated by the addition of H2O2, indicating that the COSthPBAP nanophotosensitizers had ROS sensitivity. In addition, the Ce6 release rate from the COSthPBAP nanophotosensitizers accelerated in the presence of H2O2. The SO generation was also higher in the nanophotosensitizers than in the free Ce6. Furthermore, the COSthPBAP nanophotosensitizers showed a higher intracellular Ce6 uptake ratio and ROS generation in all types of oral cancer cells. They efficiently inhibited the viability of oral cancer cells under light irradiation, but they did not significantly affect the viability of either normal cells or cancer cells in the absence of light irradiation. The COSthPBAP nanophotosensitizers showed a tumor-specific delivery capacity and fluorescence imaging of KB tumors in an in vivo animal tumor imaging study. We suggest that COSthPBAP nanophotosensitizers are promising candidates for the imaging and treatment of oral cancers.

Heavy metal removal using an advanced removal method to obtain recyclable paper incineration ash.

Various agents, including ethylenediaminetetraacetic acid, oxalic acid, citric acid, and HCl, were applied to remove heavy metals from raw paper incineration ash and render the ash recyclable. Among these prepared agent solutions, ethylenediaminetetraacetic acid showed the highest efficiency for Pb removal, while oxalic acid showed the highest efficiencies for Cu, Cd, and As removal. Additionally, three modes of an advanced removal method, which involved the use of both ethylenediaminetetraacetic acid and oxalic acid, were considered for use at the end of the rendering process. Among these three modes of the advanced removal method, that which involved the simultaneous use of ethylenediaminetetraacetic acid and oxalic acid, i.e., a mixture of both solutions, showed the best heavy metal removal efficiencies. In detail, 11.9% of Cd, 10% of Hg, 28.42% of As, 31.29% of Cu, and 49.19% of Pb were removed when this method was used. Furthermore, the application of these three modes of the advanced removal method resulted in a decrease in the amounts of heavy metals eluted and brought about an increase in the CaO content of the treated incineration ash, while decreasing its Cl content. These combined results enhanced the solidification effect of the treated incineration ash. Thus, it was confirmed that the advanced removal method is a promising strategy by which recyclable paper incineration ash can be obtained.

Optimization of a renewable hydrogen production system from food waste: A combination of anaerobic digestion and biogas reforming.

In this study, hydrogen production using food waste was optimized by investigating the effect of agitator types in anaerobic digestion reactors and catalysts for biogas reforming. The applied agitators were pitched blade and hydrofoil, and their effect on homogeneity was estimated using computational fluid dynamics. Reactors with different agitators were operated for 60 days for biogas production. Increased biogas production was observed in the reactor equipped with a hydrofoil agitator owing to its high homogeneity. In addition, Ni-CeZrO2 catalysts promoted with La2O3, CaO, or MgO were investigated for stable hydrogen production during the biogas reforming reaction using simulated gas based on biogas from the anaerobic digestion equipped the hydrofoil. Among the promoted catalysts, the MgO-promoted Ni-CeZrO2 catalyst displayed the best results for hydrogen production without significant deactivation. The stable catalytic performance of the MgO-promoted catalyst resulted from the close interaction between Ni and MgO, and its high oxygen storage capacity. Thus, 1216 L hydrogen and 646 L carbon monoxide were produced per kilogram volatile solid via the hydrogen production system that included anaerobic digestion and biogas reforming.

Nutritional and Functional Properties of Fermented Mixed Grains by Solid-State Fermentation with Bacillus amyloliquefaciens 245.

Fermented foods have several advantages, including increased nutritional value, improved bioavailability, and functional health properties. We examined that these outcomes were also observed in fermented mixed grains (FMG) containing wheat germ, wheat bran, oats, brown rice, barley, quinoa, and lentils following solid-state fermentation (SSF) by Bacillus amyloliquefaciens 245. The metabolic profile during fermentation was screened using capillary electrophoresis time-of-flight mass spectrometry (CE-TOF-MS). The amino acids were quantitatively measured for the validation of the changes in metabolites. The activity of enzymes (e.g., amylase, protease, and fibrinolysis) and antioxidant capacity was also assessed to elucidate the functionality of FMG. The essential amino acid contents gradually increased as fermentation progressed. As the metabolites involved in the urea cycle and polyamine pathway were changed by fermentation, arginine was used as a substance to produce citrulline, ornithine, and agmatine. FMG showed dramatic increases in enzyme activity. FMG incubated for 36 h also displayed higher total phenolic contents and free radical scavenging ability than MG. The data suggest that FMG produced by Bacillus amyloliquefaciens 245 possess improved nutritional and functional quality, leading to their potential use as dietary supplements.

Cloning and Heterologous Expression of the ß-Galactosidase Gene from Bifidobacterium longum RD47 in B. bifidum BGN4.

The gene encoding ß-galactosidase was cloned from Bifidobacterium longum RD47 with combinations of several bifidobacterial promoters and expressed in B. bifidum BGN4. Among the recombinant bifidobacteria, BGN4+G1 showed the highest ß-galactosidase level, for which the hydrolytic activity was continuously 2.5 to 4.2 times higher than that of BGN4 and 4.3 to 9.6 times higher than that of RD47. The ß-galactosidase activity of BGN4+G1 was exceedingly superior to that of any of the other 35 lactic acid bacteria. When commercial whole milk and BGN4+G1 were reacted, BGN4+G1 removed nearly 50% of the lactose in the milk by the 63-h time point, and a final 61% at 93 h. These figures are about twice the lactose removal rate of conventional fermented milk. As for the reaction of commercial whole milk and crude enzyme extract from BGN4+G1, the ß-galactosidase of BGN4+G1 eliminated 51% of the lactose in milk in 2 h. As shown below, we also compared the strengths and characteristics of the strong bifidobacterial promoters reported by previous studies.

Improvement of electroporation-mediated transformation efficiency for a Bifidobacterium strain to a reproducibly high level.

Bifidobacteria are representative probiotics which are defined as live microorganisms that confer a health benefit on the host. Because of their safety and healthfulness when applied to humans, bifidobacteria are suitable as genetically engineered bacteria for applications to benefit human physiology and pathology. However, molecular biological studies of bifidobacteria have been limited due to insufficient genetic tools including effective transformation methods. The aim of this study is to improve the electroporation-mediated transformation efficiency of bifidobacteria to a reproducibly high level. The crucial factors that determine electroporation efficiency are the restriction-modification system, together with the cell wall and cell membrane structure of the bacteria. We optimized the bifidobacterial electroporation conditions by focusing on these factors as well as the amount of plasmid DNA used, the electrical parameters and the bacterial growth phase. As a result, the electroporation efficiency of B. bifidum BGN4 drastically and consistently increased from 103 to 105 CFU / µg DNA. The most significant factor for increasing the electroporation efficiency was the cell wall weakening mediated by NaCl, which improved the electroporation frequency by 20 times. Because the optimized electrotransformation conditions reported here should be widely applicable to other Bifidobacterium species, these could promote the extensive genetic manipulation of the various Bifidobacterium species in future studies.

Mediator Kinase Disruption in MED12-Mutant Uterine Fibroids From Hispanic Women of South Texas.

Context: Mutations in the gene encoding Mediator complex subunit MED12 are dominant drivers of uterine fibroids (UFs) in women of diverse racial and ethnic origins. Previously, we showed that UF-linked mutations in MED12 disrupt its ability to activate cyclin C-CDK8/19 in Mediator. However, validation of Mediator kinase disruption in the clinically relevant setting of MED12-mutant UFs is currently lacking. Objective: The objective of this study was twofold. First, to extend the ethnic distribution profile of MED12 mutations by establishing their frequency in UFs from Hispanic women of South Texas. Second, to examine the impact of MED12 mutations on Mediator kinase activity in patient-derived UFs. Methods: We screened 219 UFs from 76 women, including 170 tumors from 57 Hispanic patients, for MED12 exon 2 mutations, and further examined CDK8/19 activity in Mediator complexes immunoprecipitated from MED12 mutation-negative and MED12 mutation-positive UFs. Results: MED12 exon 2 mutations in UFs from Hispanic women are somatic in nature, predominantly monoallelic, and occur at high frequency (54.1%). We identified a minimal cyclin C-CDK8 activation domain on MED12 spanning amino acids 15 through 80 that includes all recorded UF-linked mutations in MED12, suggesting that disruption of Mediator kinase activity is a principal biochemical defect arising from these pathogenic alterations. Analysis of Mediator complexes recovered from patient UFs confirmed this, revealing that Mediator kinase activity is selectively impaired in MED12-mutant UFs. Conclusions: MED12 mutations are important drivers of UF formation in Hispanic women of South Texas. MED12 mutations disrupt Mediator kinase activity, implicating altered CDK8/19 function in UF pathogenesis.

Oncogenic exon 2 mutations in Mediator subunit MED12 disrupt allosteric activation of cyclin C-CDK8/19.

Somatic mutations in exon 2 of the RNA polymerase II transcriptional Mediator subunit MED12 occur at high frequency in uterine fibroids (UFs) and breast fibroepithelial tumors as well as recurrently, albeit less frequently, in malignant uterine leimyosarcomas, chronic lymphocytic leukemias, and colorectal cancers. Previously, we reported that UF-linked mutations in MED12 disrupt its ability to activate cyclin C (CycC)-dependent kinase 8 (CDK8) in Mediator, implicating impaired Mediator-associated CDK8 activity in the molecular pathogenesis of these clinically significant lesions. Notably, the CDK8 paralog CDK19 is also expressed in myometrium, and both CDK8 and CDK19 assemble into Mediator in a mutually exclusive manner, suggesting that CDK19 activity may also be germane to the pathogenesis of MED12 mutation-induced UFs. However, whether and how UF-linked mutations in MED12 affect CDK19 activation is unknown. Herein, we show that MED12 allosterically activates CDK19 and that UF-linked exon 2 mutations in MED12 disrupt its CDK19 stimulatory activity. Furthermore, we find that within the Mediator kinase module, MED13 directly binds to the MED12 C terminus, thereby suppressing an apparent UF mutation-induced conformational change in MED12 that otherwise disrupts its association with CycC-CDK8/19. Thus, in the presence of MED13, mutant MED12 can bind, but cannot activate, CycC-CDK8/19. These findings indicate that MED12 binding is necessary but not sufficient for CycC-CDK8/19 activation and reveal an additional step in the MED12-dependent activation process, one critically dependent on MED12 residues altered by UF-linked exon 2 mutations. These findings confirm that UF-linked mutations in MED12 disrupt composite Mediator-associated kinase activity and identify CDK8/19 as prospective therapeutic targets in UFs.

Effects of Ojeok-san on the Pharmacokinetics of Celecoxib at Steady-state in Healthy Volunteers.

Ojeok-san is a frequently used herbal medication for the management of osteoarthritic pain. We evaluated the effect of Ojeok-san on the pharmacokinetics of celecoxib at steady-state in healthy individuals. An open-label, fixed-sequence, two-period, two-treatment cross-over study was conducted. In period I, the individuals received celecoxib capsule 200 mg once daily for 4 days. In period II, only Ojeok-san (14.47 g/pack, three times daily) was administered for 4 days, followed by co-administration with celecoxib for 4 days. On the fourth (final) day of administration, Ojeok-san was administered as a single dose. The blood samples for pharmacokinetic evaluation were collected for up to 48 hr after the administration of celecoxib in each study period. Of the 22 enrolled individuals, 20 individuals completed the study. In the presence of Ojeok-san, the systemic exposure of celecoxib was decreased. The geometric mean ratios ([celecoxib + Ojeok-san]/celecoxib) and the 90% confidence intervals for the maximum plasma concentration (Cmax ) and the area under the plasma concentration-time curve during dosing interval (AUCτ ) of celecoxib at steady-state were 0.725 (0.620-0.848) and 0.885 (0.814-0.962), respectively. The changes in the mean of the Cmax and AUCτ of celecoxib were greater in intermediate metabolizers of cytochrome 2C9 (CYP2C9) than in normal metabolizers. Our results suggested that the Cmax and AUCτ of celecoxib were reduced by Ojeok-san co-administration. This finding may be beneficial to determine the required adjustment of celecoxib dosage when co-administered with Ojeok-san.

Characteristics of speech production in patients with T1 glottic cancer who underwent laser cordectomy or radiotherapy.

PURPOSE: Laser cordectomy (LC) or radiotherapy (RT) is often recommended in the early stage of laryngeal cancer. We conducted perceptual and acoustic analysis to compare sustained vowel and stop consonants since there is no article evaluating both the sustained vowel and stop consonants. Eventually, we might determine which management is superior in terms of speech production. SUBJECTS AND METHODS: A total of 28 patients who underwent LC and RT for early T1 glottic cancer were selected. The sustained vowel /a/ and bilabial stop consonants were used to assess the perceptual scores. The fundamental frequency (Fo), jitter, shimmer and noise-to-harmonic ratio (NHR) levels for sustained vowels were evaluated. Voice onset time (VOT), vowel duration (VD) and closure duration of the bilabial plosives were analyzed. A receiver operating characteristic curve analysis was used to evaluate significant results statistically. RESULTS: The GRBAS and discrimination scores were not significantly different between two groups. Fo and jitter were significantly higher in the LC than RT. The cut-off value was statistically higher in the LC group and statistically lower in the RT group. The VOT was significantly longer in the LC than RT. The cut-off value of the /pipida/ VOT was statistically longer in the LC group and statistically shorter in the RT group. CONCLUSIONS: The differences may have been due to muscular fibrosis after RT. Movements of vocal cords with fibrosis were sluggish, when impulsion developed to pronounce the initial /p/ sound, so the VOT was shortened and the VD was longer after RT.

Hispolon as an inhibitor of TGF-ß-induced epithelial-mesenchymal transition in human epithelial cancer cells by co-regulation of TGF-ß-Snail/Twist axis.

Hispolon (HPL), isolated from Phellinus linteus, has been used to treat various types of pathology, including inflammation, gastroenteric disorders, lymphatic diseases and numerous cancer subtypes. HPL has previously been reported to demonstrate a significant therapeutic efficacy against various types of cancer cells, including melanoma, leukemia, hepatocarcinoma, bladder and gastric cancer cells. However, its potential role in the epithelial-mesenchymal transition (EMT) has not been demonstrated. The present study investigated the effects of HPL on the EMT. Transforming growth factor ß (TGF-ß) induced enhanced cell migration and invasion, EMT-associated phenotypic changes. In the present study, HPL recovered the reduction of E-cadherin expression level in TGF-ß treated cancer cells, which was regulated by the expression of Snail and Twist. HPL downregulated Snail and Twist, an effect that was enhanced by TGF-ß. These findings provide novel evidence that HPL suppresses cancer cell migration and invasion by inhibiting EMT. Therefore, HPL may be a potent anticancer agent, inhibiting metastasis.