Aquitalea aquatilis sp. nov., isolated from Jungwon waterfall.

A Gram-stain-negative, facultative anaerobic, motile, short rods and yellow-pigmented bacterium, designated strain THG-DN7.12T, was isolated from water collected at Jungwon waterfall on Yongmun mountain, Republic of Korea. According to 16S rRNA gene sequence comparisons, strain THG-DN7.12T was found to be most closely related to Aquitalea denitrificans 5YN1-3T (98.9 % sequence similarity), Aquitalea magnusonii TRO-001DR8T (98.7 %) and Aquitalea pelogenes P1297T (98.0 %). The DNA-DNA relatedness between strain THG-DN7.12T and its phylogenetically closest neighbours was below 70.0 %. The strain's DNA G+C content was 59.7 mol%. The major polar lipid was found to be phosphatidylethanolamine. Summed feature 3 (C16 : 1 ω7c and/or C16 : 1 ω6c) and C16 : 0 were identified as the major fatty acids. Ubiquinone Q-8 was detected as the only respiratory quinone. These data supported the affiliation of strain THG-DN7.12T to the genus Aquitalea. Strain THG-DN7.12T was distinguished from related Aquitalea species by physiological and biochemical tests. Therefore, the novel isolate represents a novel species, for which the name Aquitalea aquatilis sp. nov. is proposed, with THG-DN7.12T as the type strain (=KACC 18847T=CCTCC AB 2016185T).

Development of a cyclosporin A derivative with excellent anti-hepatitis C virus potency.

Synthetic modification of cyclosporin A at P3-P4 positions led to the discovery of NIM258, a next generation cyclophilin inhibitor with excellent anti-hepatitis C virus potency, with decreased transporter inhibition, and pharmacokinetics suitable for coadministration with other drugs. Herein is disclosed the evolution of the synthetic strategy to from the original medicinal chemistry route, designed for late diversification, to a convergent and robust development synthesis. The chiral centers in the P4 fragment were constructed by an asymmetric chelated Claisen rearrangement in the presence of quinidine as the chiral ligand. Identification of advanced crystalline intermediates enabled practical supply of key intermediates. Finally, macrocyclization was carried out at 10% weight concentration by a general and unconventional "slow release" concept.

The effects of Jawoongo soap on skin improvement.

BACKGROUND: Jawoongo is used to treat and prevent skin issues such as dry and keratinization disorders, burns, trauma, pigmentation, scarring, and inflammatory skin conditions. In this study, the efficacy and safety of 0.47% Jawoongo extract-containing soap (JAUN-CS) were assessed in terms of skin improvement effects such as cleansing, moisturizing, sebum secretion management, and skin elasticity enhancement. METHODS: Twenty healthy adult men and women aged 20-60 years old took part in the study. Before and after using JAUN-CS, the participants were divided into groups, and various skin improvement effects were measured utilizing machines such as the Corneometer, Tewameter TM 300, and Visioscan. A dermatologist analyzed the product's safety in accordance with Frosch & Kligman and the Cosmetic, Toiletry, and Fragrance Association (CTFA) rules. RESULTS: Using JAUN reduced the amount of base and point makeup by 25.7% and 76.7%, respectively. Also, JAUN showed a great facial exfoliation effect by removing the old and lifted skin keratins by 84.7% and 20.3%, respectively. Impurities in facial pores decreased by 58%, too. Furthermore, JAUN increased the moisture content of deep skin and skin surface by 3.5% and 74.0%, and skin elasticity by 2.8%. Skin tone, skin texture, skin radiance, and skin barrier all showed improvements of 3.3%, 20.0%, 15.0%, and 115.2%, respectively. Lastly, cleansing with JAUN successfully enhanced the condition of the youth triangle by 7.6%, while TEWL significantly decreased by 52.7%. Neither the JAUN nor the control group soap showed any adverse reactions, such as erythema or allergies, during the testing period. CONCLUSIONS: The results of this study demonstrated that JAUN is safe for human use and has various skin-improving properties, making Jawoongo a promising natural material for the development of functional cosmetics in the future.

The Potential Teeth Bleaching and Halitosis Prevention Effects of Pediococcus inopinatus THK-30, a Kimchi-Derived Lactic Acid Bacterium: In Vitro Study.

BACKGROUND: Recent developments in addressing dental aesthetic concerns, encompassing issues like teeth discoloration and halitosis, underscore the demand for safer alternative solutions. PURPOSE: This study aims to confirm the effects of lactic acid bacteria (LAB) from kimchi on artificial teeth bleaching and their potential impact in terms of preventing halitosis-related bacteria. MATERIALS AND METHODS: To evaluate the antimicrobial effects against oral pathogens, disc diffusion tests and broth microdilution methods were used. Additionally, crystal violet analysis was performed to confirm the biofilm inhibition effect. The bleaching effects on stained artificial teeth were analyzed using the CIEDE2000 colorimetric method. Statistical analyses were performed using GraphPad Prism 9 with one-way and two-way ANOVA, with the significance level set at α < 0.05. RESULTS: The strain THK-30, isolated from kimchi, exhibited antibacterial activity against Streptococcus mutans, Porphyromonas gingivalis, and Fusobacterium nucleatum, and was identified as Pediococcus inopinatus. Moreover, THK-30 showed a synergistic antibacterial effect against Gram-negative oral pathogens with 8% sodium hexametaphosphate (SHMP). In the stained artificial teeth bleaching test and artificial teeth biofilm inhibition test, the cell-free supernatant of THK-30 displayed significant teeth bleaching effects and caused the inhibition of biofilm formation, both independently and in combination with SHMP 8%. CONCLUSIONS: This study has demonstrated the potential applicability of LAB in teeth discoloration and halitosis. These findings are poised to provide a foundation for the development of research pertaining to the control of oral bacteria.

Scoparone inhibits PMA-induced IL-8 and MCP-1 production through suppression of NF-kappaB activation in U937 cells.

Scoparone is a major component of the shoot of Artemisia capillaris (Compositae), which has been used for the treatment of hepatitis and biliary tract infection in oriental countries. In this study, the effects of scoparone on the expression of interleukin-8 (IL-8) and monocyte chemotactic protein-1 (MCP-1) and activation of nuclear factor-kappaB (NF-kappaB) were examined in U937 human monocytes activated with phorbol 12-myristate 13-acetate (PMA). Scoparone (5-100 microM) had no cytotoxic effect in unstimulated cells and concentration-dependently reversed PMA-induced toxicity in the cells stimulated with PMA. Scoparone concentration-dependently reduced the release of IL-8 and MCP-1 protein and expression of IL-8 and MCP-1 mRNA levels induced by PMA. Moreover, scoparone inhibited the levels of NF-kappaB-DNA complex and NF-kappaB activity in the cells stimulated with PMA in a concentration-dependent manner. Scoparone dose-dependently inhibited the phosphorylation of IkappaBalpha and nuclear translocation of NF-kappaB1 p50, RelA p65, and c-Rel p75. These data suggest that scoparone may inhibit the expression of chemokines (IL-8 and MCP-1) in PMA-stimulated U937 cells and a potential mechanism of scoparone may be inhibition of NF-kappaB activation, which is linked to inhibition of NF-kappaB subunits (NF-kappaB1 p50, RelA p65, and c-Rel p75) translocation via suppression of IkappaBalpha phosphorylation.

An efficient and practical N-methylation of amino acid derivatives.

[reaction: see text] An efficient and practical N-methylation of amino acid derivatives with dimethyl sulfate in the presence of sodium hydride and a catalytic amount of water is described. Reaction of water with sodium hydride generated highly reactive dry sodium hydroxide, which led to much faster reaction rates than powdered sodium hydroxide itself.

Cyclin D1 expression and patient outcome after tamoxifen therapy in estrogen receptor positive metastatic breast cancer.

Cyclin D1 expression is closely related with ER status in breast cancer. We executed this study to evaluate whether therapeutic response to tamoxifen varies with levels of cyclin D1 expression in 66 ER positive breast cancer patients having solitary bone metastasis. Treatment response to tamoxifen and correlation between cyclin D1 expression and biologic data of the patients were analyzed. Cyclin D1 expression was detected in 46 patients (69.7%) and significantly reduced in poorly differentiated cancer (p=0.023). Patients with cyclin D1-expressing tumors showed better response to tamoxifen but the difference was not statistically significant. Cyclin D1 expression was associated with differentiation of the breast cancer but not useful in discriminating a good responder to tamoxifen treatment.

Expression of CD44 and cyclin D1 in fine needle aspiration cytology of papillary thyroid carcinoma.

OBJECTIVE: To compare the expression pattern of CD44 and cyclin D1 immunostaining in fine needle aspiration specimens of papillary carcinoma of the thyroid and nonpapillary lesions. STUDY DESIGN: The study was performed on 80 fine needle aspiration cytologic smears of thyroid lesion retrospectively using monoclonal antibodies and on histologic material from a proportion of cases. RESULTS: Most papillary carcinomas expressed intense cell membrane or diffuse cytoplasmic staining for CD44 (97.8%). Focal immunoreactivity was observed in follicular neoplasms (28.5%) and nodular goiter (4.7%). There was no difference in CD44 immunostaining between follicular carcinoma and adenoma. Cyclin D1 was expressed in the nuclei of most papillary carcinomas (79.2%). Focal nuclear immunoreactivity was noted in nodular goiters (23.5%) and follicular neoplasms (10%). In resected specimens, all papillary carcinomas (19 cases) showed intense membranous or granular CD44 immunoreactivity. Focal cyclin D1 expression was noted in 52.6%. There was no difference in CD44 and cyclin D1 expression between the group of papillary carcinomas with regional lymph node metastasis as compared to those without metastasis. Positive staining for both CD44 and cyclin D1 would strongly favor papillary carcinoma, although further studies on cytologic material are necessary to verify this diagnostic approach. CONCLUSION: Most papillary carcinomas express CD44 and cyclin D1, whereas it is less common in follicular neoplasms and nodular goiter. This may be helpful in diagnostically difficult cases.

Thrombolytic Therapy Using Urokinase for Management of Central Venous Catheter Thrombosis.

PURPOSE: The management of central venous catheters (CVCs) and catheter thrombosis vary among centers, and the efficacy of the methods of management of catheter thrombosis in CVCs is rarely reported. We investigated the efficacy of bedside thrombolysis with urokinase for the management of catheter thrombosis. MATERIALS AND METHODS: We retrospectively reviewed data from patients who had undergone CVC insertion by a single surgeon in a single center between April 2012 and June 2014. We used a protocol for the management of CVCs and when catheter thrombosis was confirmed, 5,000 U urokinase was infused into the catheter. RESULTS: A total of 137 CVCs were inserted in 126 patients. The most common catheter-related complication was thrombosis (12, 8.8%) followed by infection (8, 5.8%). Nine of the 12 patients (75%) with catheter thrombosis were recanalized successfully with urokinase. The rate of CVC recanalization was higher in the peripherally inserted central catheter (PICC) group (87.5%) than the chemoport group (50%). Reintervention for catheter-related thrombosis was needed in only 2.2% of patients when thrombolytic therapy using urokinase was applied. Age <60 years (P=0.035), PICC group (P=0.037) and location of the catheter tip above the superior vena cava (P=0.044) were confirmed as independent risk factors for catheter thrombosis. CONCLUSION: Thrombolysis therapy using urokinase could successfully manage CVC thrombosis. Reintervention was rarely needed when a protocol using urokinase was applied for the management of CVC thromboses.

Comparison of CVF (Cyclophosphamide+Vinorelbine+5-Fluorouracil) and CMF (Cyclophosphamide+Methotrexate+5-Fluorouracil) Adjuvant Chemotherapy in Early Breast Cancer.

PURPOSE: Our study aimed to evaluate the feasibility of adjuvant cyclophosphamide/vinorelbine/5-fluorourail (CVF) chemotherapy as an alternative to cyclophosphamide/methotrexate/5-fluorouracil (CMF) chemotherapy for treating early breast cancer. METHODS: One hundred and forty-nine patients were randomly assigned to CMF or CVF adjuvant chemotherapy for treating their early stage breast cancer between September 2000 and December 2007. The disease-free survival (DFS), the overall survival (OS), and the toxicity profiles of both groups were compared. RESULTS: Sixty-seven patients underwent CMF chemotherapy whereas 82 patients underwent CVF chemotherapy. The DFS and OS were 88 months (95% confidence interval [CI], 76-101 months) and 94 months (95% CI, 83-104 months), respectively for the CMF group, and 97 months (95% CI, 93-101 months), and 101 months (95% CI, 98-104 months), respectively for the CVF group. However, those survival gains of the CVF group were not statistically significant (p-value=0.069 for the DFS and 0.99 for the OS). The CVF group showed a favorable toxicity profile in terms of the grade 3/4 hematologic toxicities as compared to that of the CMF group. CONCLUSION: Clinical outcome of CVF chemotherapy was comparable to CMF with a favorable toxicity profiles. However, it is difficult to conclude the feasibility of CVF regimen because of small number of studied patients.

An efficient and large-scale enantioselective synthesis of PNP405: a purine nucleoside phosphorylase inhibitor.

An efficient and large-scale enantioselective synthesis of PNP405 (1), a purine nucleoside phosphorylase inhibitor, is described. This synthesis of 1 involved eight steps starting from o-fluorophenylacetic acid with a 21.6% overall yield and >99.5% enantiopurity. The key stereogenic center with (R)-configuration was created using Evans' asymmetric alkylation methodology. This synthesis also features the racemization-free reductive removal of the chiral auxiliary in 5 using sodium borohydride, protection of the gamma-cyano alcohol 6 as the trityl ether by a new water-assisted tritylation with trityl chloride and triethylamine or with trityl alcohol and catalytic trifluoroacetic acid, and an efficient one-pot cyclo-guanidinylation of 10 using cyanamide as the guanidinylating agent.

Therapeutic effect of topical application of linoleic acid and lincomycin in combination with betamethasone valerate in melasma patients.

Melasma is an acquired symmetric hypermelanosis characterized by irregular light-to gray-brown macules and patches on sun-exposed areas. Many therapeutic agents are available but are unsatisfactory. Recently, it has been demonstrated that lincomycin (LM) and linoleic acid (LA) can inhibit melanogenesis in vitro. Our purpose was to investigate the clinical efficacy of topical application of LM and LA in combination with betamethasone valerate (BV) in melasma patients. Forty-seven Korean female adults with clinically diagnosed melasma were enrolled in a 6-week, double-blind, randomized clinical trial. Patients were treated with one application of the vehicle (group A), 2% LM mixed with 0.05% BV (group B), or 2% LM mixed with 0.05% BV and 2% LA (group C) on the face every night. Determination of efficacy was based on the Melasma Area and Severity Index (MASI) score and objective assessment (no effect, mild, moderate, or excellent) at intervals of 2 weeks until the end of the study at 6 weeks. After 6 weeks, in comparison with the pre-treatment MASI score, the average MASI score of group C decreased to 68.9%, compared with 98% in group A (p<0.05) and 85.4% in group B. There was no statistically significant difference between group A and group B. Seven patients (43.7%) in group C revealed more than moderate improvement in objective assessment, compared with none in group A and two patients (12.5%) in group B. There were no significant side effects. Topical application of linoleic acid is considered to be effective in the treatment of melasma patients.

Prognostic implication of cyclin E expression and its relationship with cyclin D1 and p27Kip1 expression on tissue microarrays of node negative breast cancer.

BACKGROUND AND OBJECTIVES: Altered expression of cell-cycle regulators is prevalent in clinical breast cancer. This study was performed to analyze the impact of cyclin E expression to the outcome of breast cancer together with cyclin D1 and p27Kip1. METHODS: The correlation between cyclin D1/E and p27Kip1 expression was analyzed in tissue arrays of 175 node-negative breast cancers treated by the same chemotherapy composed of fluorouracil, cyclophosphamide, and methotrexate. Data from the immunohistochemical assays of three molecules were correlated and were analyzed with clinical outcome of the patients. RESULTS: Cyclin E expression was observed in 48 (27.4%) of 175 breast carcinomas. Cyclin E expression was significantly increased in young age patients and poorly differentiate tumors. Expression of cyclin E was significantly increased in cyclin D1 expressing tumors (P = 0.034). p27Kip1 expression was preserved above the 50% level in 87 tumors (49.7%) and was inversely correlated with cyclin E expression (P = 0.042). Ki67 labeling index was significantly increased in cyclin E-expressing tumors (P = 0.033) and was inversely related with p27Kip1 expression. In multivariate survival analysis, cyclin E expression was significant for the prediction of poor survival of the patients. CONCLUSIONS: Cyclin E expression was associated with poor prognosis and intimately correlated with the expression of cyclin D1 and p27Kip1. Integration of TMA technology allowed a high-throughput analysis for correlating molecular in situ findings with clinico-pathologic information.

E2F1 expression is related with the poor survival of lymph node-positive breast cancer patients treated with fluorouracil, doxorubicin and cyclophosphamide.

The expressions of E2F1 and retinoblastoma protein (pRB) were analyzed in 165 lymph node-positive breast cancers. All patients underwent adjuvant chemotherapy with fluorouracil, doxorubicin and cyclophosphamide (FAC). E2F1 was expressed in 43.6% and pRB was expressed in 46.1%. E2F1 expression was significantly increased in pRB-expressing tumors and was associated with an S-phase fraction. By univariate survival analyses, E2F1 expression and ER were identified as significant prognostic factors for disease recurrence and patient survival. E2F1 was the only significant prognostic factor of patient outcome after FAC chemotherapy by multivariate analysis.