The Neuroprotective Effects of Dendropanax morbifera Water Extract on Scopolamine-Induced Memory Impairment in Mice.

This study investigated the neuroprotective effects of Dendropanax morbifera leaves and stems (DMLS) water extract on scopolamine (SCO)-induced memory impairment in mice. First, we conducted experiments to determine the protective effect of DMLS on neuronal cells. Treatment with DMLS showed a significant protective effect against neurotoxicity induced by Aß(25-35) or H2O2. After confirming the neuroprotective effects of DMLS, we conducted animal studies. We administered DMLS orally at concentrations of 125, 250, and 375 mg/kg for 3 weeks. In the Y-maze test, SCO decreased spontaneous alternation, but treatment with DMLS or donepezil increased spontaneous alternation. In the Morris water-maze test, the SCO-treated group showed increased platform reach time and decreased swim time on the target platform. The passive avoidance task found that DMLS ingestion increased the recognition index in short-term memory. Furthermore, memory impairment induced by SCO reduced the ability to recognize novel objects. In the Novel Object Recognition test, recognition improved with DMLS or donepezil treatment. In the mouse brain, except for the cerebellum, acetylcholinesterase activity increased in the SCO group and decreased in the DMLS and donepezil groups. We measured catalase and malondialdehyde, which are indicators of antioxidant effectiveness, and found that oxidative stress increased with SCO but was mitigated by DMLS or donepezil treatment. Thus, our findings suggest that ingestion of DMLS restored memory impairment by protecting neuronal cells from Aß(25-35) or H2O2-induced neurotoxicity, and by reducing oxidative stress.

Randomized phase III trial of a neoadjuvant regimen of four cycles of adriamycin plus cyclophosphamide followed by four cycles of docetaxel (AC4-D4) versus a shorter treatment of three cycles of FEC followed by three cycles of docetaxel (FEC3-D3) in node-positive breast cancer (Neo-shorter; NCT02001506).

PURPOSE: To determine whether six cycles of FEC3-D3 has a comparable efficacy to eight of AC4-D4. METHODS: The enrolled patients (pts) were clinically diagnosed with stage II or III breast cancer. The primary endpoint was a pathologic complete response (pCR), and the secondary endpoints were 3 year disease-free survival (3Y DFS), toxicities, and health-related quality of life (HRQoL). We calculated that 252 pts were needed in each treatment group to enable the detection of non-inferiority (non-inferiority margin of 10%). RESULTS: In terms of ITT analysis, 248 pts were finally enrolled. The 218 pts who completed the surgery were included in the current analysis. The baseline characteristics of these subjects were well balanced between the two arms. By ITT analysis, pCR was achieved in 15/121 (12.4%) pts in the FEC3-D3 arm and 18/126 (14.3%) in the AC4-D4 arm. With a median follow up of 64.1 months, the 3Y DFS was comparable between the two arms (75.8% in FEC3-D3 vs. 75.6% in AC4-D4). The most common adverse event (AE) was Grade 3/4 neutropenia, which arose in 27/126 (21.4%) AC4-D4 arm pts vs 23/121 (19.0%) FEC3-D3 arm cases. The primary HRQoL domains were similar between the two groups (FACT-B scores at baseline, P = 0.35; at the midpoint of NACT, P = 0.20; at the completion of NACT, P = 0.44). CONCLUSION: Six cycles of FEC3-D3 could be an alternative to eight of AC4-D4. Trial registration ClinicalTrials.gov NCT02001506. Registered December 5,2013. https://clinicaltrials.gov/ct2/show/NCT02001506.

The efficacy of adjuvant chemotherapy with capecitabine and cisplatin after surgery in locally advanced esophageal squamous cell carcinoma: a multicenter randomized phase III trial.

There is limited evidence for the effectiveness of adjuvant chemotherapy in esophageal squamous cell carcinoma (ESCC). This study aimed to assess whether adjuvant capecitabine and cisplatin improve survival compared to surgery alone among patients with locally advanced ESCC. This is a multicenter randomized controlled trial. Patients were eligible if they underwent curative resection for ESCC staged T2-4 or N1 and M0 according to the TNM cancer staging system sixth edition. The intervention group received four cycles of adjuvant chemotherapy (capecitabine: 1,000 mg/m 2 b.i.d for 14 days, and intravenous cisplatin: 75 mg/m2 at day 1, every 3 weeks). A total of 136 patients were randomly assigned to either the adjuvant chemotherapy group (n = 68) or surgery-alone group (n = 68). Seven patients who rejected chemotherapy after randomization were excluded from the final analysis. The cumulative incidence of recurrence within 18 months after surgery was significantly lower in the adjuvant chemotherapy group than in the surgery-alone group (hazard ratio [HR]: 0.49; 95% confidence interval (CI): 0.25-0.95]. However, the 5- and 10-year disease-free survival did not differ between treatment groups (HR: 0.84; 95% CI: 0.53-1.34 and HR: 0.76; 95% CI: 0.50-1.18, respectively). Adjuvant chemotherapy after curative resection in patients with locally advanced ESCC reduced early recurrence but had no statistically significant increase in the long-term disease-free survival. Due to the limited sample size of this study, additional randomized controlled trials with larger sample sizes are necessary.

Solanum melongena L. Extract Protects Retinal Pigment Epithelial Cells from Blue Light-Induced Phototoxicity in In Vitro and In Vivo Models.

N-retinylidene-N-retinylethanolamine (A2E) accumulation in the retina is a prominent marker of retinal degenerative diseases. Blue light exposure is considered as an important factor contributing to dry age-related macular degeneration (AMD). Eggplant and its constituents have been shown to confer health benefits, but their therapeutic effects on dry AMD remain incompletely understood. In this study, we showed that an extract of Solanum melongena L. (EPX) protected A2E-laden ARPE-19 cells against blue light-induced cell death via attenuating reactive oxygen species. Transcriptomic analysis demonstrated that blue light modulated the expression of genes associated with stress response, inflammation, and cell death, and EPX suppressed the inflammatory pathway induced by blue light in A2E-laden ARPE-19 cells by inhibiting the nuclear translocation of nuclear factor kappa B and transcription of pro-inflammatory genes (CXCL8 and IL1B). The degradation of intracellular A2E was considered the major mechanism underlying the protective effect of EPX. Moreover, chlorogenic acid isolated from EPX exerted protective effects against blue light-induced cell damage in A2E-laden ARPE-19 cells. In vivo, EPX administration in BALB/c mice reduced the fundus damage and degeneration of the retinal layer in a blue light-induced retinal damage model. Collectively, our findings suggest the potential role of Solanum melongena L. extract for AMD treatment.

Root extract of Angelica reflexa B.Y.Lee reduces allergic lung inflammation by regulating Th2 cell activation.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditionally, the roots of Angelica reflexa B.Y.Lee (AR) have been used to treat cough, phlegm, neuralgia, and arthralgia in Northeast Asia. AIM OF THE STUDY: The anti-asthmatic effect of AR root extract (ARE) was determined using a murine airway allergic inflammation model and the primary T cell polarization assay. MATERIALS AND METHODS: To evaluate the anti-asthmatic effect of ARE, inflammatory cell infiltration was determined histologically and inflammatory mediators were measured in bronchoalveolar lavage fluid (BALF). Furthermore, the effects of AREs on Th2 cell differentiation and activation were determined by western blotting and flow cytometry. RESULTS: Asthmatic phenotypes were alleviated by ARE treatment, which reduced mucus production, inflammatory cell infiltration (especially eosinophilia), and type 2 cytokine levels in BALF. ARE administration to mice reduced the number of activated Th2 (CD4+CD25+) cells and level of GATA3 in the lungs. Furthermore, ARE treatment inhibited the differentiation of Th2 cells in primary cell culture systems via interferon regulatory factor 4 (IRF4) signaling. CONCLUSIONS: Our findings indicate that the anti-asthmatic effect of AREs is mediated by the reduction in Th2 cell activation by regulating IRF4.

Treatment strategy and outcomes in locally advanced head and neck squamous cell carcinoma: a nationwide retrospective cohort study (KCSG HN13-01).

BACKGROUND: By investigating treatment patterns and outcomes in locally advanced head and neck squamous cell carcinoma (LA-HNSCC), we aimed at providing valuable insights into the optimal therapeutic strategy for physicians in real-world practice. METHODS: This is a multi-institutional study enrolled the patients with stage III to IVB LA-HNSCC, except for nasopharyngeal carcinoma, from 2004 to 2015 in thirteen referral hospitals capable of multidisciplinary care. RESULTS: A total of 445 LA-HNSCC patients were analyzed. The median age was 61 years (range, 24-89). The primary tumor location was the oropharynx in 191 (43%), oral cavity in 106 (24%), hypopharynx in 64 (14%), larynx in 57 (13%) and other sites in 27 (6%). The most common stage was T2 in 172 (39%), and N2 in 245 (55%). Based on treatment intents, 229 (52%) of the patients received definitive concurrent chemoradiotherapy (CCRT) and 187 (42%) underwent surgery. Approximately 158 (36%) of the study population received induction chemotherapy (IC). Taken together, 385 (87%) of the patients underwent combined therapeutic modalities. The regimen for definitive CCRT was weekly cisplatin in 58%, 3-weekly cisplatin in 28% and cetuximab in 3%. The preferred regimen for IC was docetaxel with cisplatin in 49%, and docetaxel, cisplatin plus fluorouracil in 27%. With a median follow-up of 39 months, one-year and two-year survival rates were 89 and 80%, respectively. Overall survival was not significantly different between CCRT and surgery group (p = 0.620). CONCLUSIONS: In patients with LA-HNSCC, the majority of patients received combined therapeutic modalities. Definitive CCRT, IC then definitive CCRT, and surgery followed by adjuvant CCRT or radiotherapy are the preferred multidisciplinary strategies in real-world practice.

First-in-Human Phase I Study of Aprutumab Ixadotin, a Fibroblast Growth Factor Receptor 2 Antibody-Drug Conjugate (BAY 1187982) in Patients with Advanced Cancer.

BACKGROUND: Fibroblast growth factor receptor (FGFR) 2 is overexpressed in several tumor types, including triple-negative breast cancer and gastric cancer, both of which have a high unmet medical need. Aprutumab ixadotin (BAY 1187982) is the first antibody-drug conjugate (ADC) to target FGFR2 and the first to use a novel auristatin-based payload. OBJECTIVE: This first-in-human trial was conducted to determine the safety, tolerability, and maximum tolerated dose (MTD) of aprutumab ixadotin in patients with advanced solid tumors from cancer indications known to be FGFR2-positive. PATIENTS AND METHODS: In this open-label, multicenter, phase I dose-escalation trial (NCT02368951), patients with advanced solid tumors received escalating doses of aprutumab ixadotin (starting at 0.1 mg/kg body weight), administered intravenously on day 1 of every 21-day cycle. Primary endpoints included safety, tolerability, and the MTD of aprutumab ixadotin; secondary endpoints were pharmacokinetic evaluation and tumor response to aprutumab ixadotin. RESULTS: Twenty patients received aprutumab ixadotin across five cohorts, at doses of 0.1-1.3 mg/kg. The most common grade ≥ 3 drug-related adverse events were anemia, aspartate aminotransferase increase, proteinuria, and thrombocytopenia. Dose-limiting toxicities were thrombocytopenia, proteinuria, and corneal epithelial microcysts, and were only seen in the two highest dosing cohorts. The MTD was determined to be 0.2 mg/kg due to lack of quantitative data following discontinuations at 0.4 and 0.8 mg/kg doses. One patient had stable disease; no responses were reported. CONCLUSIONS: Aprutumab ixadotin was poorly tolerated, with an MTD found to be below the therapeutic threshold estimated preclinically; therefore, the trial was terminated early. CLINICALTRIALS. GOV IDENTIFIER: NCT02368951.

Anti-asthmatic effects of lepidii seu Descurainiae Semen plant species in ovalbumin-induced asthmatic mice.

ETHNOPHARMACOLOGICAL EVIDENCE: Lepidii seu Descurainiae Semen (LDS) is used as a traditional herbal medicine in northeast Asia, mainly in Korea, Japan, and China to treat lung disorders including coughs and phlegm caused by acute and chronic airway inflammation. AIM OF THE STUDY: Recently, interest regarding health problems incurred by air pollution has rapidly grown. Herbal medicines are being considered as alternative agents to treat various diseases. In the present study, we evaluated and compared the anti-inflammatory effects of LDS, which is derived from Lepidium apetalum Willd. extracts (LAE) and Descurainia sophia (L.) Webb ex Prantl extracts (DSE), on allergic airway inflammation. MATERIALS AND METHODS: We established an ovalbumin-induced asthmatic mouse model to evaluate the efficacy of LDS extracts. We performed histological examination and measured relevant inflammatory mediators and cells in bronchoalveolar lavage fluid and lung. Furthermore, we conducted an in vitro T helper 2 (Th2) polarization assay, flow cytometry, and western blot analysis. RESULTS: Asthmatic phenotypes were attenuated by LDS extract treatments. LDS extract administration significantly reduced mucus production, inflammatory cell infiltration into airways, and eosinophil activation. Furthermore, LDS extracts reduced the expression of type 2 cytokines and inhibited differentiation and activation of Th2 cells. CONCLUSION: LDS alleviated eosinophilic inflammation by inhibiting Th2 cell differentiation, and DSE was more effective in attenuating allergic lung inflammation than LAE.

Codonopsis lanceolata attenuates allergic lung inflammation by inhibiting Th2 cell activation and augmenting mitochondrial ROS dismutase (SOD2) expression.

Allergic asthma is a chronic inflammatory disease induced by the inhalation of allergens, which trigger the activation of T helper type 2 (Th2) cells that release Th2 cytokines. Recently, herbal medicines are being considered a major source of novel agents to treat various diseases. In the present study, we evaluated the anti-asthmatic effects of a Codonopsis lanceolata extract (CLE) and the mechanisms involved in its anti-inflammatory effects. Treatment with CLE reduced infiltration of inflammatory cells, especially eosinophils, and the production of mucus in lung tissues. Levels of Th2 cytokines, such as IL-4, IL-5, and IL-13, and chemokines were also decreased following treatment with CLE. Moreover, Th2 cell proportion in vivo and differentiation in vitro were reduced as evidenced by the decreased expression of GATA3+. Furthermore, the expression of superoxide dismutase (SOD)2, a mitochondrial ROS (mROS) scavenger, was increased, which was related to Th2 cell regulation. Interestingly, treatment with CLE increased the number of macrophages in the lungs and enhanced the immune-suppressive property of macrophages. Our findings indicate that CLE has potential as a novel therapeutic agent to inhibit Th2 cell differentiation by regulating mROS scavenging.

Anthriscus sylvestris root extract reduces allergic lung inflammation by regulating interferon regulatory factor 4-mediated Th2 cell activation.

ETHNOPHARMACOLOGICAL RELEVANCE: Anthriscus sylvestris L. Hoffmann (AS) is a perennial plant that grows in Asia and Eastern Europe. Its dried root is used to treat conditions such as asthma, bronchitis, and cough. AIM OF THE STUDY: The present study investigated the anti-inflammatory effects of whole AS extract (ASE) on allergic lung inflammation in vitro and in vivo as well as the underlying mechanisms. MATERIALS AND METHODS: We used an ovalbumin (OVA)-induced asthma mouse model and in vitro primary T helper (Th)2 polarization system. Five groups of 8-week-old female C57BL/6 mice were divided into the following groups: saline control, or OVA-induced allergic asthma with vehicle, ASE (100 or 200 mg/kg), or dexamethasone (5 mg/kg) treatment for 7 days. RESULTS: ASE attenuated mucus secretion in airway epithelial cells, inflammatory cell infiltration, eosinophilia, and Th2 cytokine levels in bronchoalveolar lavage fluid. Mice administered ASE showed reductions in the activated cluster of differentiation 4+ T cell population and GATA-binding protein-3 gene expression in the lung, and diminished Th2 cell differentiation and activation in vitro. Furthermore, ASE-treated mice showed decreased interleukin-6 and interferon regulatory factor (IRF)4 expression, with corresponding reductions in nitric oxide levels in the lungs of asthmatic mice and in stimulated RAW cells. CONCLUSION: ASE exerts anti-asthmatic effects by inhibiting IRF4 expression and thereby suppressing Th2 cell activation.

Identification of Epigenetic Mechanisms Involved in the Anti-Asthmatic Effects of Descurainia sophia Seed Extract Based on a Multi-Omics Approach.

Asthma, a heterogeneous disease of the airways, is common around the world, but little is known about the molecular mechanisms underlying the interactions between DNA methylation and gene expression in relation to this disease. The seeds of Descurainia sophia are traditionally used to treat coughs, asthma and edema, but their effects on asthma have not been investigated by multi-omics analysis. We undertook this study to assess the epigenetic effects of ethanol extract of D. sophia seeds (DSE) in an ovalbumin (OVA)-induced mouse model of asthma. We profiled genome-wide DNA methylation by Methyl-seq and characterized the transcriptome by RNA-seq in mouse lung tissue under three conditions: saline control, OVA-induced, and DSE-treated. In total, 1995 differentially methylated regions (DMRs) were identified in association with anti-asthmatic effects, most in promoter and coding regions. Among them, 25 DMRs were negatively correlated with the expression of the corresponding 18 genes. These genes were related to development of the lung, respiratory tube and respiratory system. Our findings provide insights into the anti-asthmatic effects of D. sophia seeds and reveal the epigenetic targets of anti-inflammatory processes in mice.

Protective effects of a traditional herbal extract from Stellaria dichotoma var. lanceolata against Mycobacterium abscessus infections.

Stellaria dichotoma var. lanceolata (SdLv), a member of the Caryophyllaceae, is a traditional herbal medicine that has been used to treat fever, night sweats, and malaria in East Asia. Inflammation plays an essential role in both host defense and pathogenesis during infection by diverse intracellular pathogens. Herein, we showed that an herbal extract from SdLv effectively attenuated inflammatory responses from infection of Mycobacterium abscessus (Mab), but not Toxoplasma gondii (T. gondii). In primary murine macrophages, Mab infection resulted in the rapid activation of nuclear factor (NF)-κB and mitogen-activated protein kinase (MAPK), as well as in the generation of proinflammatory cytokines, such as tumor necrosis factor α and interleukin-6, which were all significantly inhibited by pretreatment with SdLv. However, herbal extracts from Bupleurum chinense DC. (Buch) or Bupleurum falcatum L. (Bufa) did not affect M. abs-induced activation of proinflammatory responses. Importantly, we demonstrated that generation of intracellular reactive oxygen species, which are important signaling intermediaries in the activation of NF-κB and the MAPK signaling pathway, was rapidly increased in Mab-infected macrophages, and this was effectively suppressed by pretreatment with SdLv, but not Buch and Bufa. We further found that the treatment of Buch and Bufa, but not SdLv, led to the activation of NF-κB and the MAPK signaling pathway and the generation of intracellular reactive oxygen species. Moreover, oral administration of SdLv significantly reduced lethality in Mab-infected mice. Collectively, these results suggest the possible use of SdLv as an effective treatment for Mab infection.

Postoperative adjuvant chemotherapy is associated with a lower incidence of colorectal adenomas in patients with previous colorectal cancer.

BACKGROUND AND AIMS: The effects of chemotherapeutic agents on the development of colorectal adenomas in patients with previous colorectal cancer (CRC) are not defined. Therefore, we evaluated the potential effect of adjuvant chemotherapy on the incidence of colorectal adenomas in patients with previous CRC. METHODS: We selected patients with low-risk stage II CRC with or without postoperative 5-fluorouracil-based adjuvant chemotherapy to reduce selection bias. Among 1808 patients with stage II CRC who underwent colonoscopic surveillance after curative resection of CRC between 2006 and 2013, 192 patients were retrospectively enrolled in this study after matching for age and sex. The patients were divided into 96 patients receiving and 96 patients not receiving 5-fluorouracil-based chemotherapy. RESULTS: Forty patients (41.7%) exhibited colorectal adenomas among 96 patients who received adjuvant chemotherapy, compared with 50 patients (52.1%) with colorectal adenomas among 96 patients who received surgery only. The incidence rate of advanced adenoma was significantly lower in the chemotherapy group than in the nonchemotherapy group (3.1% vs 10.4%, P = .044). After adjustment for clinically relevant factors such as body mass index, aspirin use, metformin use, number of follow-up colonoscopies, and operation type, adjuvant chemotherapy was found to be associated with a decreased incidence of advanced adenoma (odds ratio, .151; 95% confidence interval, .035-.653; P = .011) in patients with stage II CRC. CONCLUSIONS: The results showed that chemotherapy in patients with CRC may be associated with a lower risk of colorectal advanced adenoma development.

Protective effect of ixerisoside A against UVB-induced pro-inflammatory cytokine production in human keratinocytes.

Human skin is the first line of defense for the protection of the internal organs of the body from different stimuli. Ultraviolet B (UVB), one of the harmful radiations for skin, is widely known to induce abnormally increased cytokine release from keratinocytes leading to inflammatory skin disorders. IL-6 and IL-8 induce an acute-phase response and stimulate leukocyte infiltration in the skin. Previous studies have shown that chronic exposure to UVB radiation increases cyclooxygenase-2 (COX­2) expression through various cell signaling pathways, resulting in skin cancer. Recent studies have shown that the activation of extracellular signal-regulated kinase (ERK), c-Jun NH2-terminal kinase (JNK), and p38 MAPK is strongly correlated with acute inflammation and development of skin cancer caused by an increased expression of COX-2. Ixerisoside A (IXA) is an active constituent of Ixeris dentata of the Compositae (Asteraceae) family. The effect of IXA on skin inflammation has yet to be elucidated. To determine the anti-inflammatory effects of IXA, we examined its effect on UVB-induced pro-inflammatory cytokine production in human keratinocytes (HaCaT cells) by observing these cells in the presence or absence of IXA. In this study, pro-inflammatory cytokine production was determined by enzyme-linked immunosorbent assay (ELISA), reverse transcription-polymerase chain reaction (rt-pcr), and western blot analysis to evaluate the activation of mitogen-activated protein kinases (MAPKs). IXA inhibited UVB-induced production of the pro-inflammatory cytokines IL-6 and IL-8 in a dose-dependent manner. Moreover, IXA inhibited the expression of COX-2, ERK, JNK, and p38 MAPKs, indicating that the secretion of the pro-inflammatory cytokines IL-6 and IL-8, and COX-2 expression was inhibited by blocking MAPK phosphorylation. These results indicated that IXA potentially protects against UVB-induced skin inflammation.

Synergistic effects of oxyresveratrol in conjunction with antibiotics against methicillin-resistant Staphylococcus aureus.

Methicillin-resistant Staphylococcus aureus (MRSA) infection is a serious clinical problem worldwide. The aim of the present study was to examine the antimicrobial activity of oxyresveratrol (ORV) against MRSA. The antimicrobial activity of ORV was evaluated against three strains of MRSA and one methicillin-susceptible S. aureus (MSSA) strain using a minimal inhibitory concentration (MIC) assay, MTT colorimetric assay, checkerboard dilution test and time-kill assay. The MIC of ORV for all strains was moderate at 125 µg/ml. Of note, the antimicrobial activity and fractional inhibitory concentration index values of ORV were markedly increased in the presence of a non-growth inhibitory dose of certain antibiotics. Time-kill curves revealed that a combination of ORV with ciprofloxacin or with gentamicin reduced bacterial counts to below the lowest detectable limit after 24 h. These effective combinations may be used as potential antimicrobial regimens for use in the management of MRSA.

Vaccination and complementary and alternative medicine in patients with inflammatory bowel disease.

BACKGROUND/AIMS: Vaccinations in patients with inflammatory bowel disease (IBD) are recommended to prevent infectious diseases. However, there are few reports of vaccination in IBD patients in Korea. The frequency of complementary and alternative medicine (CAM) use is high despite its uncertain effectiveness. This study aimed to identify the rates of vaccination and use of CAM in patients with IBD. METHODS: A total of 219 patients attended an education session for IBD patients held at Severance Hospital on March 23, 2013. We conducted a survey on vaccination and CAM use in IBD patients; 120 patients completed the questionnaire. RESULTS: The influenza vaccination rate was 44.2% and pneumococcal vaccination rate was 4.2%. Thirty-one (66%) patients were aware of the importance of vaccination. The vaccination rate was higher in patients who were aware of the importance of vaccination compared with that in patients who were unaware of the importance of vaccination (70.1% vs. 41.7%, P=0.004). The rate of CAM use was 30.0%. The most commonly used CAMs were oral products: vitamins (33.3%), red ginseng (25.0%), and probiotics (19.4%). CONCLUSIONS: Awareness of the importance of vaccination and actual vaccination rates were low in IBD patients. Despite insufficient evidence on the effectiveness of CAMs in IBD patients, many patients used CAMs. We believe that repeated education and promotion of vaccination are important. Further large-scale studies to investigate the efficacy and safety of CAMs are warranted in patients with IBD.

The Antibacterial Assay of Tectorigenin with Detergents or ATPase Inhibitors against Methicillin-Resistant Staphylococcus aureus.

Tectorigenin (TTR) is an O-methylated isoflavone derived from the rhizome of Belamacanda chinensis (L.) DC. It is known to perform a wide spectrum of biological activities such as antioxidant, anti-inflammatory, anti-tumor. The aim of this study is to examine the mechanism of antibacterial activity of TTR against methicillin-resistant Staphylococcus aureus (MRSA). The anti-MRSA activity of TTR was analyzed in combination assays with detergent, ATPase inhibitors, and peptidoglycan (PGN) derived from S. aureus. Transmission electron microscopy (TEM) was used to monitor survival characteristics and changes in S. aureus morphology. The MIC values of TTR against all the tested strains were 125 µ g/mL. The OD(600) of each suspension treated with a combination of Triton X-100, DCCD, and NaN3 with TTR (1/10 × MIC) had been reduced from 68% to 80%, compared to the TTR alone. At a concentration of 125 µ g/mL, PGN blocked antibacterial activity of TTR. This study indicates that anti-MRSA action of TTR is closely related to cytoplasmic membrane permeability and ABC transporter, and PGN at 125 µ g/mL directly bind to and inhibit TTR at 62.5 µ g/mL. These results can be important indication in study on antimicrobial activity mechanism against multidrug resistant strains.

Changes in serum hydroxyvitamin D levels of breast cancer patients during tamoxifen treatment or chemotherapy in premenopausal breast cancer patients.

BACKGROUND: We investigated the effect of breast cancer adjuvant treatment on vitamin D status, as measured by serum hydroxyvitamin D (25OHD). METHODS: Premenopausal patients (n=483) diagnosed with non-metastatic breast cancer in 2009 at Asan Medical Center had serum 25OHD levels prospectively analysed at diagnosis and 6 and 12months after surgery. We excluded patients who took vitamin D supplements or received neoadjuvant chemotherapy. Vitamin D sufficiency was defined as a serum level of ⩾30ng/ml, insufficiency as 20-29ng/ml and deficiency as <20ng/ml. RESULTS: Compared with baseline serum 25OHD, patients who received chemotherapy had decreased serum 25OHD levels at 6months (-5.52ng/ml, p=0.003) and 12months (-1.24ng/ml, p=0.517) and patients who received anti-hormone therapy had significantly increased serum 25OHD levels at 6months (+3.00ng/ml, p=0.681) and 12months (+6.47ng/ml, p=0.002, respectively). Among patients who received chemotherapy, 49.5% were vitamin D sufficient at diagnosis but only 26.9% were sufficient 6months after finishing chemotherapy and this percentage increased to 45.2% at 12months. CONCLUSIONS: Vitamin D levels decrease during chemotherapy but recover after treatment ends. Anti-hormone therapy with tamoxifen causes serum vitamin D levels to increase. Whether the increased serum vitamin D affects the antitumour effect of the tamoxifen has yet to be determined.

Combination Therapy of Sophoraflavanone B against MRSA: In Vitro Synergy Testing.

Sophoraflavanone B (SPF-B), a known prenylated flavonoid, was isolated from the roots of Desmodium caudatum. The aim of this study was to determine the antimicrobial synergism of SPF-B combined with antibiotics against methicillin-resistant Staphylococcus aureus (MRSA). MRSA, a multidrug-resistant pathogen, causes both hospital- and community-acquired infections worldwide. The antimicrobial activity of SPF-B was assessed by the broth microdilution method, checkerboard dilution test, and time-kill curve assay. The MIC of SPF-B for 7 strains of S. aureus ranges from 15.6 to 31.25 µ g/mL determined. In the checkerboard method, the combinations of SPF-B with antibiotics had a synergistic effect; SPF-B markedly reduced the MICs of the ß -lactam antibiotics: ampicillin (AMP) and oxacillin (OXI); aminoglycosides gentamicin (GET); quinolones ciprofloxacin (CIP) and norfloxacin (NOR) against MRSA. The time-kill curves assay showed that a combined SPF-B and selected antibiotics treatment reduced the bacterial counts below the lowest detectable limit after 24 h. These data suggest that the antibacterial activity of SPF-B against MRSA can be effectively increased through its combination with three groups of antibiotics ( ß -lactams, aminoglycosides, and quinolones). Our research can be a valuable and significant source for the development of a new antibacterial drug with low MRSA resistance.

Anti-inflammatory effects of tectroside on UVB-induced HaCaT cells.

Ultraviolet B (UVB) irradiation causes skin damage and inflammation by inducing the secretion of various cytokines, which are immune regulators produced by cells. To prevent skin inflammation, keratinocytes that have been irreversibly damaged by UVB must be eliminated through apoptosis. Ixeris dentata (I. dentata) (family Asteraceae) is a perennial medicinal herb indigenous to Korea. It is used in Korea, China and Japan to treat indigestion, pneumonia, diabetes, hepatitis, contusions and tumors. Guaiane-type sesquiterpene lactones were isolated from the whole extract of I. dentata. This led to the isolation of the anti-inflammatory sesquiterpene lactone compound tectroside (TES), which was tested on a human keratinocyte cell line. To determine the anti-inflammatory effects of TES, we examined its influence on UVB-induced pro-inflammatory cytokine production in human keratinocytes (HaCaT cells) by observing these cells in the presence or absence of TES. In the present study, pro-inflammatory cytokine production was determined by performing enzyme-linked immunosorbent assay, reverse transcription-polymerase chain reaction and western blot analysis to evaluate the activation of mitogen-activated protein kinases (MAPKs). TES inhibited UVB-induced production of the pro-inflammatory cytokines interleukin (IL)-6 and IL-8 in a dose-dependent manner. In addition, TES inhibited the expression of cyclooxygenase (COX)-2 and the phosphorylation of c-Jun NH2-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) MAPKs, suggesting that it inhibits the secretion of the pro-inflammatory cytokines IL-6 and IL-8 and COX-2 expression by blocking MAPK phosphorylation. These results suggest that TES can potentially protect against UVB-induced skin inflammation.