Multidrug-resistant tuberculosis in South Korea: a retrospective analysis of national registry data in 2011-2015.

BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB) poses a threat to public health as a result of high treatment costs and unsatisfactory outcomes.OBJECTIVE: To elucidate trend, demographic and clinical characteristics and treatment outcomes of patients with MDR-TB between 2011 and 2015 in South Korea.METHOD: Data of patients with MDR-TB diagnosed between 1 January 2011 and 31 December 2015 were retrieved from the nationwide Internet-based TB notification system and analysed retrospectively.RESULTS: During the study period, 5192 MDR-TB patients were notified. We identified an increasing number of MDR-TB patients among foreign populations (from 1.3% to 7.7%), decreasing resistance rates to other anti-TB drugs (e.g., resistance to pyrazinamide, from 40.9% to 28.2%), a decreasing interval from treatment initiation to negative conversion of sputum culture (from 165.7 to 103.7 days) and shortening of treatment duration (719.7 to 613.2 days). However, treatment success rates did not change, and had an average of 65.7%.CONCLUSION: Despite decreasing resistance rates to other drugs and faster treatment responses, treatment outcomes did not improve during the study period. Strict management of MDR-TB patients on treatment should be adopted to improve treatment outcomes.

Ultrafast nematic-orbital excitation in FeSe.

The electronic nematic phase is an unconventional state of matter that spontaneously breaks the rotational symmetry of electrons. In iron-pnictides/chalcogenides and cuprates, the nematic ordering and fluctuations have been suggested to have as-yet-unconfirmed roles in superconductivity. However, most studies have been conducted in thermal equilibrium, where the dynamical property and excitation can be masked by the coupling with the lattice. Here we use femtosecond optical pulse to perturb the electronic nematic order in FeSe. Through time-, energy-, momentum- and orbital-resolved photo-emission spectroscopy, we detect the ultrafast dynamics of electronic nematicity. In the strong-excitation regime, through the observation of Fermi surface anisotropy, we find a quick disappearance of the nematicity followed by a heavily-damped oscillation. This short-life nematicity oscillation is seemingly related to the imbalance of Fe 3dxz and dyz orbitals. These phenomena show critical behavior as a function of pump fluence. Our real-time observations reveal the nature of the electronic nematic excitation instantly decoupled from the underlying lattice.

Epac2a-null mice exhibit obesity-prone nature more susceptible to leptin resistance.

BACKGROUND: The exchange protein directly activated by cAMP (Epac), which is primarily involved in cAMP signaling, has been known to be essential for controlling body energy metabolism. Epac has two isoforms: Epac1 and Epac2. The function of Epac1 on obesity was unveiled using Epac1 knockout (KO) mice. However, the role of Epac2 in obesity remains unclear. METHODS: To evaluate the role of Epac2 in obesity, we used Epac2a KO mice, which is dominantly expressed in neurons and endocrine tissues. Physiological factors related to obesity were analyzed: body weight, fat mass, food intake, plasma leptin and adiponectin levels, energy expenditure, glucose tolerance, and insulin and leptin resistance. To determine the mechanism of Epac2a, mice received exogenous leptin and then hypothalamic leptin signaling was analyzed. RESULTS: Epac2a KO mice appeared to have normal glucose tolerance and insulin sensitivity until 12 weeks of age, but an early onset increase of plasma leptin levels and decrease of plasma adiponectin levels compared with wild-type mice. Acute leptin injection revealed impaired hypothalamic leptin signaling in KO mice. Consistently, KO mice fed a high-fat diet (HFD) were significantly obese, presenting greater food intake and lower energy expenditure. HFD-fed KO mice were also characterized by greater impairment of hypothalamic leptin signaling and by weaker leptin-induced decrease in food consumption compared with HFD-fed wild-type mice. In wild-type mice, acute exogenous leptin injection or chronic HFD feeding tended to induce hypothalamic Epac2a expression. CONCLUSIONS: Considering that HFD is an inducer of hypothalamic leptin resistance and that Epac2a functions in pancreatic beta cells during demands of greater work load, hypothalamic Epac2a may have a role in facilitating leptin signaling, at least in response to higher metabolic demands. Thus, our data indicate that Epac2a is critical for preventing obesity and thus Epac2a activators may be used to manage obesity and obesity-mediated metabolic disorders.

Evaluation of anti-acne properties of phloretin in vitro and in vivo.

OBJECTIVE: This study aimed to investigate the anti-acne properties of phloretin in vitro and in vivo. METHODS: Anti-microbial activity against Propionibacterium acnes (P. acnes), Propionibacterium granulosum (P. granulosum) and Staphylococcus epidermidis (S. epidermidis) were observed by the minimum inhibitory concentration (MIC) and disc diffusion methods. The anti-inflammatory effects were studied in HaCaT cells based on P. acnes-induced inflammatory mediators, including PGE2 and COX-2, examined through enzyme-linked immunosorbent assay (ELISA) and luciferase reporter gene assay. Thirty healthy subjects with whiteheads participated in the clinical study. Comedo counting, and the amount of sebum and porphyrin were measured before treatment and following 4 consecutive weeks of treatment with phloretin. RESULTS: Phloretin showed anti-microbial activities against P. acnes, P. granulosum, S. epidermidis with the MIC of 0.5, 0.5 and 0.25 mg mL(-1) , respectively. P. acnes-induced activation of the COX-2 promoter was markedly attenuated by phloretin treatment. Consistent with these results, inhibition of PGE2 production was also observed. In 1-month, placebo-controlled trials, phloretin showed clinically and statistically significant reduction of comedo counts and sebum output level. Compared to before treatment, whiteheads, blackheads, papules, sebum output level and amount of sebum and porphyrin were significantly decreased at 4 weeks in the test group. CONCLUSIONS: This study revealed that phloretin inhibits the growth of P. acnes, P. granulosum, and S. epidermidis. In addition, we demonstrated that phloretin attenuates COX-2 and PGE2 expression during the P. acnes-induced upregulation of inflammatory signalling. Clinical studies further suggested that treatment with formulations containing phloretin confers anti-acne benefits. Based on these results, we suggest that phloretin may be introduced as a possible acne-mitigating agent.

Altered serotonin transporter binding potential in patients with obsessive-compulsive disorder under escitalopram treatment: [11C]DASB PET study.

BACKGROUND: Obsessive-compulsive disorder (OCD) is a chronic, relapsing mental illness. Selective serotonin reuptake inhibitors block serotonin transporters (SERTs) and are the mainstay of treatment for OCD. SERT abnormalities are reported in drug-free patients with OCD, but it is not known what happens to SERT levels during treatment. This is important as alterations in SERT levels in patients under treatment could underlie poor response, or relapse during or after treatment. The aim of the present study was first to validate a novel approach to measuring SERT levels in people taking treatment and then to investigate SERT binding potential (BP) using [11C]DASB PET in patients with OCD currently treated with escitalopram in comparison with healthy controls. METHOD: Twelve patients and age- and sex-matched healthy controls were enrolled. The patients and healthy controls underwent serial PET scans after administration of escitalopram and blood samples for drug concentrations were collected simultaneously with the scans. Drug-free BPs were obtained by using an inhibitory E max model we developed previously. RESULTS: The inhibitory E max model was able to accurately predict drug-free SERT BP in people taking drug treatment. The drug-free BP in patients with OCD currently treated with escitalopram was significantly different from those in healthy volunteers [Cohen's d = 0.03 (caudate), 1.16 (putamen), 1.46 (thalamus), -5.67 (dorsal raphe nucleus)]. CONCLUSIONS: This result extends previous findings showing SERT abnormalities in drug-free patients with OCD by indicating that altered SERT availability is seen in OCD despite treatment. This could account for poor response and the high risk of relapse in OCD.

Traditional Yangsaeng oriental health promotion in patients with cardiovascular disease.

BACKGROUND: A traditional Korean health behavior regimen, 'Yangsaeng' is an ancient Chinese concept that incorporates health promoting behaviours. AIM: The purpose of this study was to test a hypothesized model that identified the effects of activity status, internal health locus of control, and resilience on Yangsaeng among patients with cardiovascular disease. METHODS: Secondary data were utilized in this study. Originally, 543 Korean patients with cardio-vascular disease were recruited from general hospitals, although only 532 were included in this study. Path analysis was performed using AMOS 17.0. RESULTS: Resilience was significantly associated with and accounted for 37% of the variance in Yangsaeng. Activity status and internal health locus of control were significantly associated with and accounted for 4% of the variance in resilience. LIMITATIONS: Given the cross-sectional data used, the sequencing and/or direction of the relationships found remains uncertain. There may be complex interactions that were not considered. CONCLUSIONS: These results suggest that enhancing resilience is essential to foster a health-promoting lifestyle that helps prevent the recurrence of cardio-vascular disease. IMPLICATIONS FOR NURSING AND HEALTH POLICY: Nurse development of a Yangsaeng program for patients with cardiovascular disease may be a useful means of enhancing resilience in western as well as eastern cultures. This will help such patients to recognize the health benefits of improving their resilience through heightened activity levels and adopting an internal health locus of control.

Ecklonia cava promotes hair growth.

BACKGROUND: Previous studies have reported the protective effects on skin elasticity of the edible marine seaweed Ecklonia cava, which acts through regulation of both antioxidative and anti-inflammatory responses. AIM: We evaluated the effect of E. cava and one of its components, dioxinodehydroeckol, on hair-shaft growth in cultured human hair follicles and on hair growth in mice. METHODS: The MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay was used to check cell viability of human dermal papilla cells (DPCs) and outer root sheath (ORS) cells after treatment with E. cava and its metabolite, dioxinodehydroeckol. Hair-shaft growth was measured using the in vitro hair-follicle organ-culture system, in the presence or absence of E. cava and dioxinodehydroeckol. Anagen induction activity was examined by topical application of E. cava to the dorsal skin of C57BL/6 mice. Insulin-like growth factor (IGF)-1 expression was measured by reverse transcriptase PCR and ELISA. RESULTS: The proliferation activity was found to be highest for the ethyl acetate-soluble fraction of E. cava (EAFE) in DPCs and in ORS cells. Treatment with EAFE resulted in elongation of the hair shaft in cultured human hair follicles, and promoted transition of the hair cycle from the telogen to the anagen phase in the dorsal skin of C57BL/6 mice. In addition, EAFE induced an increase in IGF-1 expression in DPCs. Dioxinodehydroeckol, a component of E. cava, induced elongation of the hair shaft, an increase in proliferation of DPCs and ORS cells, and an increase in expression of IGF-1 in DPCs. CONCLUSIONS: These results suggest that E. cava containing dioxinodehydroeckol promotes hair growth through stimulation of DPCs and ORS cells.

The effects of transanal irrigation as a stepwise bowel management program on the quality of life of children with spina bifida and their caregivers.

STUDY DESIGN: Experimental, prospective study. OBJECTIVES: Fecal incontinence and constipation affect the quality of life (QOL) of children with spina bifida and their caregivers. We evaluated the clinical efficacy of a stepwise bowel management program on QOL for children with spina bifida and their caregivers. SETTING: Republic of Korea. METHODS: Between December 2010 and April 2011, 53 children with constipation, fecal incontinence or both underwent a stepwise bowel management program at our spina bifida clinic. The children and their caregivers were evaluated before and after this program using a self-administered questionnaire. RESULTS: Among the children, 11.3% received only oral laxatives and controlled well, 88.7% received transanal irrigation. After this program, the mean number of episodes of fecal incontinence per week, number of diaper changes and total time for bowel care decreased from 6.9 to 0.5 (P=0.004), from 1.6 to 0.2 (P=0.001) and from 27 to 15.9 min (P=0.003), respectively. Caregivers and children were able to leave their houses more often (P=0.006), and caregivers' bothersomeness, anxiety and depression due to bowel care decreased (P<0.001). Factors related to family relationships (P=0.265) and financial impact (P=0.071) improved, but not significantly. CONCLUSIONS: We observed significant improvement in defecation symptoms and QOL scores of spina bifida patients who underwent this program. We recommend that this simple therapeutic method be considered as a safe and valid choice for the treatment of chronic constipation and fecal incontinence.

Clinical characteristics, drug resistance, and treatment outcomes among tuberculosis patients with diabetes in Peru.

OBJECTIVES: Diabetes is a risk factor for active tuberculosis (TB). Data are limited regarding the association between diabetes and TB drug resistance and treatment outcomes. We examined characteristics of TB patients with and without diabetes in a Peruvian cohort at high risk for drug-resistant TB. Among TB patients with diabetes (TB-DM), we studied the association between diabetes clinical/management characteristics and TB drug resistance and treatment outcomes. METHODS: During 2005-2008, adults with suspected TB with respiratory symptoms in Lima, Peru, who received rapid drug susceptibility testing (DST), were prospectively enrolled and followed during treatment. Bivariate and Kaplan-Meier analyses were used to examine the relationships of diabetes characteristics with drug-resistant TB and TB outcomes. RESULTS: Of 1671 adult TB patients enrolled, 186 (11.1%) had diabetes. TB-DM patients were significantly more likely than TB patients without diabetes to be older, have had no previous TB treatment, and to have a body mass index (BMI) >18.5 kg/m(2) (p<0.05). In patients without and with previous TB treatment, the prevalence of multidrug-resistant TB was 23% and 26%, respectively, among patients without diabetes, and 12% and 28%, respectively, among TB-DM patients. Among 149 TB-DM patients with DST results, 104 (69.8%) had drug-susceptible TB and 45 (30.2%) had drug-resistant TB, of whom 29 had multidrug-resistant TB. There was no association between diabetes characteristics and drug-resistant TB. Of 136 TB-DM patients with outcome information, 107 (78.7%) had a favorable TB outcome; active diabetes management was associated with a favorable outcome. CONCLUSIONS: Diabetes was common in a cohort of TB patients at high risk for drug-resistant TB. Despite prevalent multidrug-resistant TB among TB-DM patients, the majority had a favorable TB treatment outcome.

Octet-line node structure of superconducting order parameter in KFe2As2.

In iron-pnictide superconductivity, the interband interaction between the hole and electron Fermi surfaces (FSs) is believed to play an important role. However, KFe(2)As(2) has three zone-centered hole FSs and no electron FS but still exhibits superconductivity. Our ultrahigh-resolution laser angle-resolved photoemission spectroscopy unveils that KFe(2)As(2) is a nodal s-wave superconductor with highly unusual FS-selective multi-gap structure: a nodeless gap on the inner FS, an unconventional gap with "octet-line nodes" on the middle FS, and an almost-zero gap on the outer FS. This gap structure may arise from the frustration between competing pairing interactions on the hole FSs causing the eightfold sign reversal. Our results suggest that the A(1g) superconducting symmetry is universal in iron-pnictides, in spite of the variety of gap functions.

Quantitative PCR and in vivo efficacy of antibiotics in the treatment of Vibrio vulnificus infection in a mouse model.

The Centers for Disease Control and Prevention (CDC) recommend oral or intravenous doxycycline plus a third-generation cephalosporin or fluoroquinolone alone for the treatment of Vibrio vulnificus infections. Until now, no study has compared oral with parenteral administered doxycycline with respect to their in vivo efficacy. In the present work, ICR mice infected with a high dose of V. vulnificus were administered ciprofloxacin, ceftriaxone, and doxycycline. The bacterial DNA copy number in surviving and non-surviving mice was determined using quantitative polymerase chain reaction (qPCR). In this setting, ciprofloxacin was the most effective monotherapeutic drug, but a higher survival rate (50%) was achieved using the combination therapy of intraperitoneal doxycycline plus ceftriaxone. The blood of non-surviving mice at 12 h post-infection contained at least 10(4) DNA copies/µL, in contrast to 10(2) to 10(3) DNA copies/µL in surviving mice. Thus, in the treatment of V. vulnificus infections in humans, when the intravenous form of doxycycline is unavailable, ciprofloxacin might be a better option than oral doxycycline to lower mortality. In addition, our results demonstrate that qPCR can be a useful tool for identifying the V. vulnificus load in infected patients, with the DNA copy number providing a marker of either disease severity or mortality.

Genome-wide association analysis of coffee drinking suggests association with CYP1A1/CYP1A2 and NRCAM.

Coffee consumption is a model for addictive behavior. We performed a meta-analysis of genome-wide association studies (GWASs) on coffee intake from 8 Caucasian cohorts (N=18 176) and sought replication of our top findings in a further 7929 individuals. We also performed a gene expression analysis treating different cell lines with caffeine. Genome-wide significant association was observed for two single-nucleotide polymorphisms (SNPs) in the 15q24 region. The two SNPs rs2470893 and rs2472297 (P-values=1.6 × 10(-11) and 2.7 × 10(-11)), which were also in strong linkage disequilibrium (r(2)=0.7) with each other, lie in the 23-kb long commonly shared 5' flanking region between CYP1A1 and CYP1A2 genes. CYP1A1 was found to be downregulated in lymphoblastoid cell lines treated with caffeine. CYP1A1 is known to metabolize polycyclic aromatic hydrocarbons, which are important constituents of coffee, whereas CYP1A2 is involved in the primary metabolism of caffeine. Significant evidence of association was also detected at rs382140 (P-value=3.9 × 10(-09)) near NRCAM-a gene implicated in vulnerability to addiction, and at another independent hit rs6495122 (P-value=7.1 × 10(-09))-an SNP associated with blood pressure-in the 15q24 region near the gene ULK3, in the meta-analysis of discovery and replication cohorts. Our results from GWASs and expression analysis also strongly implicate CAB39L in coffee drinking. Pathway analysis of differentially expressed genes revealed significantly enriched ubiquitin proteasome (P-value=2.2 × 10(-05)) and Parkinson's disease pathways (P-value=3.6 × 10(-05)).

Programmatic management of multidrug-resistant tuberculosis: models from three countries.

BACKGROUND: Although multidrug-resistant tuberculosis (MDR-TB) is a major global health problem, there is a gap in programmatic treatment implementation. METHODS: This study describes MDR-TB treatment models in three countries--Peru, Russia and Lesotho-- using qualitative data collected over a 13-year period. RESULTS: A program analysis is presented for each country focusing on baseline medical care, initial implementation and program evolution. A pattern analysis revealed six overarching themes common to all three programs: 1) importance of baseline assessments, 2) early identification of key collaborators, 3) identification of initial locus of care, 4) minimization of patient-incurred costs, 5) targeted interventions for vulnerable populations and 6) importance of technical assistance and funding. Site commonalities and differences in each of these areas were analyzed. CONCLUSIONS: It is recommended that all programs providing MDR-TB treatment address these six areas during program development and implementation.

In vitro antimicrobial effect and in vivo preventive and therapeutic effects of partially purified lantibiotic lacticin NK34 against infection by Staphylococcus species isolated from bovine mastitis.

Lantibiotics are small (<5 kDa), polycyclic peptides produced by gram-positive bacteria; they are also known as gram-positive bacteriocins. The high antimicrobial activity of lacticins and the continuing appearance of antibiotic-resistant bacteria in recent years have resulted in a renewed interest in lantibiotics. A partially purified form of lacticin NK34 (a Lactococcus lactis product isolated from the Korean fermented fish jeotgal) was tested to determine its antimicrobial effects against Staphylococcus aureus (n=20) and coagulase-negative Staphylococcus (CNS, n=20) strains isolated from the raw milk of cows with subclinical bovine mastitis in the present study. The spot-on-lawn assay was used to identify the 2 strains from each group with the greatest lacticin NK34 susceptibility, and the minimal lethal dose (MLD) was measured in ICR (imprinting control region) mice. The preventive and therapeutic effects of lacticin NK34 on the mouse infection model were determined for the first time. Lacticin NK34 demonstrated antimicrobial effects in 14 of 20 (70%) S. aureus indicator strains and in 18 of 20 (90%) CNS strains. Staphylococcus aureus 69 and S. simulans 55 demonstrated the greatest susceptibility to lacticin NK34 in the spot-on-lawn assay. The S. aureus 69 MLD was measured at 1.53 x 10(9) cfu/mouse, whereas the S. simulans 55 MLD was 3.59 x 10(9) cfu/mouse. Mice infected experimentally with S. aureus 69 MLD or S. simulans 55 MLD were treated with lacticin NK34. Treated mice demonstrated an 80% survival rate (48 of 60 mice) compared with a survival rate of 7.5% (3 of 40 mice) in control mice treated with distilled water. These data suggest that lacticin NK34 might be useful in the control of bovine mastitis and systemic bacterial infection.

Effects of chitooligosaccharide supplementation on performance, blood characteristics, relative organ weight, and meat quality in broiler chickens.

This study was conducted to evaluate the effects of dietary supplementation with chitooligosaccharide (COS) on growth performance, blood characteristics, relative organ weight, and meat quality in broilers. A total of 480 broilers with an average initial BW of 45.04 g per chick were randomly allocated into 1 of the following 4 dietary treatments (20 broilers per pen with 6 pens per treatment): 1) CON (basal diet), 2) ANT (basal diet + 44 mg/kg of avilamycin), 3) COS0.2 (basal diet + 14 g/kg of COS), 4) COS0.4 (basal diet + 28 g/kg of COS). The experiment lasted for 5 wk and avilamycin was administered from d 0 to 21. Growth performance was measured on d 0, 21, and 35, and all other response criteria were measured on d 35. No change in feed conversion (G:F) was observed in response to any of the treatments throughout the experimental period (P > 0.05). However, BW gain and feed intake were greater (P < 0.05) in broilers provided with feed supplemented with COS than in those in the control group. In addition, broilers had significantly greater (P < 0.05) red blood cell and high-density lipoprotein cholesterol concentrations when they were provided with the COS0.4 diet, whereas the triglyceride concentration was lower (P < 0.05) in broilers in the COS0.2 treatment group. No other blood characteristics were affected by the treatments. Additionally, as the dietary COS concentration increased, the liver weight increased (P < 0.05). Conversely, as the concentrations of dietary COS increased, abdominal fat decreased (P < 0.05). Furthermore, meat yellowness decreased (P < 0.05) as the concentration of COS increased. Finally, the breast meat and abdominal fat of birds provided with feed supplemented with COS had a lower (P < 0.05) saturated fatty acid concentration but a greater concentration of total monounsaturated fatty acids (P < 0.05) than that of birds in the control. In conclusion, COS can improve the performance and breast meat quality of broilers while increasing the red blood cell and high-density lipoprotein cholesterol concentrations in blood. In addition, COS can induce a decrease in abdominal fat and improve meat quality.

Timely diagnosis of MDR-TB under program conditions: is rapid drug susceptibility testing sufficient?

Timely diagnosis and effective, safe treatment are essential to reduce transmission and improve outcomes for patients with tuberculosis. Aside from laboratory methods, many programmatic factors influence the overall turnaround time (TAT) in diagnosing multidrug-resistant tuberculosis (MDR-TB). We measured each step in the overall TAT required for MDR-TB in two of five health districts of Lima, Peru. The total TAT, from initial sputum specimen to diagnosis and appropriate treatment, was 5 months, almost twice as long as the bacteriological procedures per se. Expensive investments in laboratory technology may yield low returns unless the programmatic aspects of the diagnostic process are streamlined at the same time.

Antifungal effects of the volatile oils from Allium plants against Trichophyton species and synergism of the oils with ketoconazole.

In an attempt to develop stable and safe antifungal agents from natural products (daily foodstuffs in particular), the activities of essential oils from Allium sativum for. pekinense, A. cepa, and A. fistulosum against three Trichophyton species responsible for severe mycoses in humans were investigated and compared with activity of allicin in this study. The fungistatic activities of Allium oils were evaluated by the broth dilution method and disk diffusion assay. The combined effects of Allium oils with ketoconazole were tested by the checkerboard titer test. Among the tested oils, A. sativum for. pekinense oil exhibited the strongest inhibition of growth of T. rubrum, T. erinacei, and T. soudanense with MICs (minimum inhibiting concentrations) of 64microg/ml, while the activities of A. cepa and A. fistulosum were relatively mild. The inhibiting activities of the oils on Sabouraud agar plates were dose dependent against Trichophyton species. Additionally, these oils showed significant synergistic antifungal activity when combined with ketoconazole in the checkerboard titer test and disk diffusion test.

Anti-inflammatory effect of jeongshintang through suppression of p38 activation in human astrocytoma, U373MG cells.

Jeongshintang (JST) is a Korean herbal prescription, which has been successfully used for cerebral diseases. However, the anti-inflammatory effect of JST on Alzheimer's disease (AD) is still not fully understood. In this study, we investigated the effects of JST in attenuating the inflammatory response induced by interleukin (IL)-1beta plus beta-amyloid [1-42] fragment (A beta) in the human astrocyte cell line, U373MG. The production of IL-6, IL-8, and prostaglandin (PG)E2 was significantly increased by IL-1beta plus A beta (1-42) in a time-dependent manner (P < 0.05). JST significantly inhibited the IL-1beta plus A beta (1-42)-induced IL-6, IL-8, and PGE2 production at 24 h (P < 0.05). Maximal inhibition rate of IL-6, IL-8, and PGE2 production by JST was about 54.40%, 56.01%, and 44.06% respectively. JST (0.01-1 mg/ml) also attenuated the expression of cyclooxygenase (COX)-2 and activation of p38 MAPK induced by IL-1beta and A beta (1-42). These results demonstrated that JST has an anti-inflammatory effect, which might explain its beneficial effect in the treatment of various neurodegenerative diseases such as AD.

Dihydroartemisinin enhances radiosensitivity of human glioma cells in vitro.

PURPOSE: The antimalarial agent, artemisinin, also confers cancer-specific cytotoxic effects by reacting with ferrous iron atoms to form free radicals. Here, we investigated the radiosensitizing effects of dihydroartemisinin on glioma cells and assessed some possible mechanisms for these effects. MATERIALS AND METHODS: U373MG glioma cells treated with various concentrations of dihydroartemisinin plus radiation, and efficiency of radiosensitization was assessed by clonogenic survival assay. Expression and activity of antioxidant enzymes, glutathione-S-transferase (GST) were quantified by western blot and enzymatic activity analyses, respectively. RESULTS: Dihydroartemisinin showed higher cytotoxicity in the glioma cell lines than in the liver, breast or cervical cancer cell lines. In clonogenic survival assays, treatment with dihydroartemisinin alone dose-dependently reduced the number of U373MG colonies, while treatment with dihydroartemisinin plus gamma-irradiation showed far lower clonal survival than cultures treated with radiation or dihydroartemisinin alone. The radiosensitizing effect of dihydroartemisinin was blocked significantly by the free radical scavengers, NAC and TIRON, indicating association with dihydroartemisinin-induced ROS generation. In addition, the radiation-induced expression of endogenous GST was suppressed by treatment with dihydroartemisinin. The radiosensitizing effect of dihydroartemisinin was also markedly enhanced by the addition of holotransferrin CONCLUSION: Taken together, our results strongly suggest that dihydroartemisinin triggers production of ROS and inhibits GST activity, leading to effective and therapeutically relevant radiosensitization of human glioma cells.