Synthesis of antibacterial hydroxypropyl methylcellulose and silver nanoparticle biocomposites via solution plasma using silver electrodes.

The biocomposites of hydroxypropyl methylcellulose (HPMC)/silver nanoparticles (AgNPs) were synthesized using the solution plasma process (SPP). HPMC/AgNPs were synthesized in 1-5 % HPMC solutions using silver electrodes. UV-Vis spectroscopy showed a peak near 400 nm and the peak increased as the concentration of HPMC and discharge time increased. FTIR analysis indicated no change in the chemical structure of the HPMC based biocomposites. Spherical shaped AgNPs with size ranges about 2-18 nm and well dispersed in the porous HPMC matrices with fringed edges were observed by TEM and SEM/EDS analyses. The synthesized biocomposites were found to be thermo-stable by TGA analysis. The inhibition zones of bacterial growth formed by the HPMC/AgNPs biocomposites were in the range of 8-14.3 mm; minimal inhibition concentrations, in the range of 10-15 µg·mL-1 for Gram-negative bacteria; 25-30 µg·mL-1 for Gram-positive bacteria. The biocomposites were non-toxic to the HEK293 cells up to 125 µg·mL-1. The results indicated that the synthesis of antibacterial agents in the HPMC matrix using silver electrodes via SPP would be an efficient and safe way for the development of biopolymer based antimicrobials and wound healing biomaterials.

Zinc deficiency associated with cutaneous toxicities induced by epidermal growth factor receptor tyrosine kinase inhibitor therapy in patients with lung adenocarcinoma.

PURPOSE: Cutaneous toxicities are common adverse effects following epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) therapy. Zinc deficiency causes diverse diseases, including skin toxicities. Therefore, this study aimed to investigate the role of zinc deficiency in patients with EGFR-TKI-induced skin toxicities. EXPERIMENTAL DESIGN: This retrospective study enrolled 269 patients with diverse skin disorders who visited our hospital between January 2016 and December 2017. The skin toxicity severities and plasma zinc levels of 101 EGFR-TKI-treated cancer patients were analysed and compared with those of 43 non-EGFR-TKI-treated cancer patients and 125 patients without cancer but presenting cutaneous manifestations. Additionally, the role of zinc in erlotinib-induced skin eruptions was established in a 14-day-murine model. Clinical features were further evaluated following systemic zinc supplementation in EGFR-TKI-treated cancer patients. RESULTS: EGFR-TKI-treated patients demonstrated severe cutaneous manifestations and a significant decrease in plasma zinc levels than those of the control groups. The serum zinc level and Common Terminology Criteria for Adverse Events (CTCAE) 5.0 grading of EGFR-TKI-induced skin toxicities showed a significant negative correlation (r = -0.29; p < 0.0001). Moreover, erlotinib treatment decreased the plasma zinc levels and induced periorificial dermatitis in rats confirming zinc deficiency following EGFR-TKI treatment. Zinc supplementation to the EGFR-TKI-treated cancer patients showed a significant decrease in the CTCEA grading (p < 0.0005 for mucositis and p < 0.0.0001 for all other cases) after 8 weeks. CONCLUSIONS: Skin impairment following EGFR-TKI therapy could be ameliorated through zinc supplementation. Thus, zinc supplementation should be considered for cancer patients undergoing EGFR-TKI therapy.

Regorafenib for Taiwanese patients with unresectable hepatocellular carcinoma after sorafenib failure: Impact of alpha-fetoprotein levels.

BACKGROUND AND AIMS: Regorafenib has demonstrated its survival benefit for unresectable hepatocellular carcinoma (uHCC) patients in a phase III clinical trial. We aimed to assess the efficacy and tolerability of regorafenib and the predictors of treatment outcomes in Taiwanese patients. METHODS: We analyzed the survival, best overall response, predictors of treatment outcomes, and safety for uHCC patients who had tumor progression on sorafenib therapy and received regorafenib as salvage therapy between March 2018 and November 2020. RESULTS: Eighty-six patients with uHCC were enrolled (median age, 66.5 years; 76.7% male). The median regorafenib treatment duration was 4.0 months (95% confidence interval [CI], 3.6-4.6). The most frequently reported adverse events were hand-foot skin reaction (44.2%), diarrhea (36.0%), and fatigue (29.1%). No unpredictable toxicity was observed during treatment. The median overall survival (OS) with regorafenib was 12.4 months (95% CI, 7.8-17.0) and the median progression-free survival (PFS) was 4.2 months (95% CI, 3.7-4.7). Of 82 patients with regorafenib responses assessable, 4 patients (4.9%) achieved a partial response, and 33 (40.2%) had stable disease, leading to a disease control rate (DCR) of 45.1% (n = 37). Patients possessing baseline AFP < 400 ng/ml exhibited a markedly longer median OS, median PFS, and higher DCR compared with their counterparts (15.7 vs. 8.1 months, 4.6 vs. 3.7 months, 60.9% vs. 27.5%, respectively). Despite possessing high baseline AFP levels, patients with early AFP response (>10% reduction at 4 weeks or >20% reduction at 8 weeks after regorafenib administration) exhibited comparable treatment outcomes to those with baseline AFP < 400 ng/ml. CONCLUSIONS: The results of this real-world study verified the tolerability and efficacy of regorafenib treatment for uHCC patients who failed prior sorafenib therapy, especially for those with lower baseline AFP levels or with early AFP response.

5-Desmethylsinensetin isolated from Artemisia princeps suppresses the stemness of breast cancer cells via Stat3/IL-6 and Stat3/YAP1 signaling.

AIMS: To study 5-desmethylsinensetin exhibiting potential anticancer activity against breast cancer stem cells and the related molecular mechanism. MAIN METHODS: In this study, isolation of a cancer stem cell (CSC) inhibitor of Artemisia princeps was performed using a silica gel column, a Sephadex gel column, and high-performance liquid chromatography. A single compound was purified via activity-based isolation using mammosphere formation assays. An MTS was used to examine the proliferation of breast cancer cells, and flow cytometry was used to analyze apoptosis and cancer stem cell markers. Western blotting was used to detect the signaling pathway. RESULTS: The isolated compound was identified as 5-desmethylsinensetin using nuclear magnetic resonance and mass spectrometry. 5-Desmethylsinensetin suppresses the proliferation and mammosphere formation of breast cancer cells, reduces the subpopulations of CD44+/CD24- and ALDH1+ cancer cells, and reduces the transcription of the stemness markers Oct4, c-Myc, Nanog and CD44 in Breast CSCs. 5-Desmethylsinensetin inhibits the total and nuclear expression of Stat3 and p-Stat3, as well as the translocation of YAP1. Additionally, 5-desmethylsinensetin reduces the mRNA and protein levels of IL-6. CONCLUSION: Our results show that 5-desmethylsinensetin exhibits potential anticancer activity against breast cancer stem cells via Stat3-IL-6 and Stat3-YAP1 signaling.

Effectiveness and healthcare costs of eribulin versus capecitabine among metastatic breast cancer patients in Taiwan.

OBJECTIVE: To compare the real-world effectiveness and costs of eribulin to those of capecitabine in patients with metastatic breast cancer (MBC) pretreated with anthracyclines and taxanes. METHODS: This study extracted data from the Health and Welfare Database in Taiwan to identify MBC patients, and then eribulin and capecitabine users were matched at a 1:1 ratio by age, residential region, Charlson Comorbidity Index score, and molecular subtype of BC cell. The overall survival (OS) and time-to-treatment discontinuation (TTD) curves were plotted using the Kaplan-Meier method. Healthcare utilization and costs between the two groups were compared. RESULTS: A total of 24,550 MBC patients were identified, and 298 patients were enrolled in each group after matching. The median OS was 11.8 months for eribulin (95%CI: 11.5-13.5 months) and 15.2 months for capecitabine (95%CI: 15.3-17.9 months; HR = 1.7, p < 0.0001). The median TTD was 4.0 months for eribulin and 6.6 months for capecitabine (HR = 1.6; p < 0.0001). No significant difference was found between the two groups in patients with >4 prior chemotherapy agents (OS: HR 1.1, 95%CI 0.8-1.5; TTD: HR 1.2, 95%CI 0.9-1.7). The total healthcare costs per patient during the treatment period were NT$580,523.8 for eribulin versus NT$497,223.8 for capecitabine (p < 0.0001), and total medication costs were NT$438,335.8 and NT$348,438.4 (p < 0.0001), respectively. CONCLUSION: Although eribulin showed an attenuated effect in the real-world setting in Taiwan, it may serve as an alternative for capecitabine in a heavy pretreated population. The total healthcare and medication costs were found to be higher with eribulin treatment.

Using Guided Imagery to Relieve the Anxiety of Preschool Children Undergoing Dental Procedures.

PURPOSE: Negative experiences in dental clinics can induce anxiety in patients, and the effects are particularly pronounced in children. When behavior guidance methods (eg, direct observation, tell-show-do, and ask-tell-ask) fail, general anesthesia is an important alternative; however, the procedure of anesthesia can also induce fear and anxiety. This study assessed the effectiveness of guided imagery in relieving the anxiety associated with dental surgery in children and caregivers. DESIGN: A prospective randomized trial with two groups. METHODS: The guided imagery in this study was meant to establish a rapport between the medical team and the patient, by encouraging the child to imagine having an adventure while riding in a spacecraft. Anxiety levels and behavior were measured using five well-established scales: the modified Yale Preoperative Scale-Short Form, the State-Trait Anxiety Inventory-6 items, the Watcha score, the Pediatric Anesthesia Emergent Delirium scale, and the Posthospitalization Behavioral Questionnaire-Ambulatory Surgery. FINDINGS: The results indicate that the guided imagery had no significant effects on anxiety levels. CONCLUSIONS: Guided imagery is a low-cost, easy-to-implement, interesting exercise capable of enhancing interactions between nursing staff and children. It may also help to condition children to the environment and thereby assist them in overcoming their fears.

Betavulgarin Isolated from Sugar Beet (Beta vulgaris) Suppresses Breast Cancer Stem Cells through Stat3 Signaling.

Breast cancer is a major health problem that affects lives worldwide. Breast cancer stem cells (BCSCs) are small subpopulations of cells with capacities for drug resistance, self-renewal, recurrence, metastasis, and differentiation. Herein, powder extracts of beetroot were subjected to silica gel, gel filtration, thin layer chromatography (TLC), and preparatory high-pressure liquid chromatography (HPLC) for isolation of one compound, based on activity-guided purification using tumorsphere formation assays. The purified compound was identified as betavulgarin, using nuclear magnetic resonance spectroscopy and electrospray ionization (ESI) mass spectrometry. Betavulgarin suppressed the proliferation, migration, colony formation, and mammosphere formation of breast cancer cells and reduced the size of the CD44+/CD24- subpopulation and the expression of the self-renewal-related genes, C-Myc, Nanog, and Oct4. This compound decreased the total level and phosphorylated nuclear level of signal transducer and activator of transcription 3 (Stat3) and reduced the mRNA and protein levels of sex determining region Y (SRY)-box 2 (SOX2), in mammospheres. These data suggest that betavulgarin inhibit the Stat3/Sox2 signaling pathway and induces BCSC death, indicating betavulgarin might be an anticancer agent against breast cancer cells and BCSCs.

Thermosensitive chitosan-gelatin-based hydrogel containing curcumin-loaded nanoparticles and latanoprost as a dual-drug delivery system for glaucoma treatment.

Elevated intraocular pressure (IOP) in glaucoma is due to impairment of aqueous humor drainage via the uveoscleral or trabecular outflow pathway. Latanoprost reduces IOP by increasing the uveoscleral outflow. Despite its potency, long-term daily application of it may cause undesirable side effects and many require more than one medication for IOP control. Recent studies have suggested that oxidative stress in the trabecular meshwork (TM) play an important role in the pathogenesis of impaired trabecular outflow facility. Curcumin, a natural phenolic compound, possesses anti-oxidant and anti-inflammation properties. In this study, we developed a thermosensitive hydrogel containing latanoprost and curcumin-loaded nanoparticles (CUR-NPs), and evaluated its possible therapeutic effects with cultured human TM cells under oxidative stress. The results demonstrated that 20 µM of CUR-NPs might be the optimal concentration to treat TM cells without causing cytotoxicity. Using the newly developed system, both latanoprost and CUR-NPs displayed a sustained-release profile. Treatment with this hydrogel containing CUR-NPs effectively decreased the oxidative stress-mediated damage in TM cells via decreasing inflammation-related gene expression, mitochondrial reactive oxygen stress (ROS) production and apoptosis level. The in vivo biocompatibility revealed no signs of inflammation or damage after topical application of developed hydrogel in rabbits. These results suggest that this dual-drug delivery system might enhance both trabecular and uveoscleral outflow and is promising to develop into a novel treatment for glaucoma.

Identification of groups with poor cost-effectiveness of peginterferon plus ribavirin for naïve hepatitis C patients with a real-world cohort and database.

BACKGROUND: For decades, peginterferon and ribavirin (PegIFN/RBV) have been the standard-of-care for chronic hepatitis C virus (CHC) infection. However, the actual cost-effectiveness of this therapy remains unclear. We purposed to explore the real-world cost effectiveness for subgroups of treatment-naïve CHC patients with PegIFN/RBV therapy in a large real-world cohort using a whole population database. METHODS: A total of 1809 treatment-naïve chronic hepatitis C virus (HCV) patients (829 HCV genotype 1 [G1] and 980 HCV G2) treated with PegIFN/RBV therapies were linked to the National Health Insurance Research Database, covering the entire population of Taiwan from 1998 to 2013 to collect the total medical-care expenses of outpatient (antiviral agents, nonantiviral agents, laboratory, and consultation costs) and inpatient (medication, logistic, laboratory, and intervention costs) visits. The costs per treatment and the cost per sustained virological response (SVR) achieved were calculated. RESULTS: The average medical-care cost was USD $4823 (±$2984) per treatment and $6105 (±$3778) per SVR achieved. With SVR rates of 68.6% and 87.8%, the cost/SVR was significantly higher in G1 than those in G2 patients, respectively ($8285 vs $4663, P < .001). Treatment-naïve G1 patients of old ages, those with advanced fibrosis, high viral loads, or interleukin-28B unfavorable genotypes, or those without a rapid virological response (RVR: undetectable HCV RNA at week 4), or those with complete early virological response (cEVR: undetectable HCV RNA at week 12). Treatment-naïve G2 patients with high viral loads or without RVR or cEVR incurred significantly higher costs per SVR than their counterparts. The cost/SVR was extremely high among patients without RVR and in patients without cEVR. CONCLUSION: We investigated the real-world cost effectiveness data for different subgroups of treatment-naïve HCV patients with PegIFN/RBV therapies, which could provide useful, informative evidence for making decisions regarding future therapeutic strategies comprising costly direct-acting antivirals.

The correlation between pulse diagnosis and constitution identification in traditional Chinese medicine.

OBJECTIVES: Our study aimed to correlate pulse wave parameters such as augmentation index (AI) and heart rate variability with traditional Chinese medicine (TCM) constitution for evaluating health status. DESIGN: Out of 177 subjects, 69 healthy subjects were enrolled in the present study, and others were excluded because of cardiovascular, liver, kidney, or other diseases. Each subject was invited to complete pulse wave examination and the Constitution in Chinese Medicine Questionnaire. Independent Student's t-tests, Mann-Whitney tests, and binary logistic regression analysis were used to analyse the correlation between pulse wave parameters and TCM constitution. RESULTS: Qi-deficient individuals had higher AI (p=0.006) and lower diastolic blood pressure (p=0.011); yang-deficient individuals had lower dP/dt max (p=0.030), systolic blood pressure (p=0.020), and pulse pressure (p=0.048); and damp-heat individuals had higher subendocardial viability index (SEVI) scores (p=0.011). We then categorized the phlegm dampness and yang-deficiency individuals into the cold group and those with damp-heat and yin-deficiency into the heat group. A comparison of the two constitution groups showed higher AI in the cold group (p=0.026). Binary logistic regression analysis demonstrated that only AI was a determinant, as evidenced by the finding that an increase of one unit in AI corresponded to an increase of 5% in the odds ratio for individuals to have a cold constitution (p=0.026). CONCLUSIONS: Individuals with qi-deficient and cold constitutions had higher AI and lower SEVI, potentially reflecting an increase in arterial stiffness. This study can provide a basis for further investigation of the physiological indicators of TCM constitutions in modern medicine.

Direct medical cost of stroke in Singapore.

BACKGROUND: Globally, stroke is recognized as one of the main causes of long-term disability, accounting for approximately 5·7 million deaths each year. It is a debilitating and costly chronic condition that consumes about 2-4% of total healthcare expenditure. AIMS: To estimate the direct medical cost associated with stroke in Singapore in 2012 and to determine associated predictors. METHODS: The National Healthcare Group Chronic Disease Management System database was used to identify patients with stroke between the years 2006 and 2012. Estimated stroke-related costs included hospitalizations, accident and emergency room visits, outpatient physician visits, laboratory tests, and medications. RESULTS: A total of 700 patients were randomly selected for the analyses. The mean annual direct medical cost was found to be S$12 473·7, of which 93·6% were accounted for by inpatient services, 4·9% by outpatient services, and 1·5% by A&E services. Independent determinants of greater total costs were stroke types, such as ischemic stroke (P = 0·005), subarachnoid hemorrhage (P < 0·001) and intracerebral haemorrhage (P < 0·001), shorter poststroke period, more than one complications (P = 0·045), and a greater number of comorbidities (P = 0·001). CONCLUSION: There is a considerable economic burden associated with stroke in Singapore. The type of stroke, length of poststroke period, and stroke complications and comorbidities are found to be associated with the total costs. Efforts to reduce inpatient costs and to allocate health resources to focus on the primary prevention of stroke should become a priority.

Cost-effectiveness of dabigatran and rivaroxaban compared with warfarin for stroke prevention in patients with atrial fibrillation.

PURPOSE: This study aimed to evaluate the cost-effectiveness of dabigatran and rivaroxaban compared with warfarin for the prevention of stroke in patients with atrial fibrillation (AF) in Singapore. METHODS: A Markov model was constructed to compare the lifetime costs, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs) of dabigatran 110 and 150 mg, rivaroxaban 20 mg and adjusted-dose warfarin from the perspective of the Singapore healthcare system, using clinical data from published studies, utilities from a patient-reported survey and costs from hospital databases. The target population was a hypothetical cohort of 65-year-old AF patients with no contraindications to anticoagulation. RESULTS: In the base-case analysis, the QALYs were 8.75 with warfarin, 8.73 with dabigatran 110 mg, 8.82 with dabigatran 150 mg, and 9.33 with rivaroxaban. The costs were Singapore dollar (SG$) 34,648 for warfarin, SG$54,919 for dabigatran 110 mg, SG$50,484 for dabigatran 150 mg and SG$51,975 for rivaroxaban. The ICER of rivaroxaban versus warfarin was SG$29,697 (US$26,727) per QALY. Rivaroxaban and warfarin had extended dominance over the high-dose dabigatran. The low-dose dabigatran was dominated by warfarin. Deterministic sensitivity analyses showed that the ICER of rivaroxaban versus warfarin was sensitive to cost of rivaroxaban and utilities for rivaroxaban and warfarin. Probability sensitivity analysis demonstrated that the probability of rivaroxaban being the optimal choice was 97.8% and 99.5% at a willingness-to-pay threshold of SG$65,000 (US$58,500) and SG$130,000 (US$117,000) per QALY, respectively. CONCLUSION: Rivaroxaban may be a cost-effective alternative to warfarin for the prevention of stroke in patients with AF in Singapore.

Antidepressant-Like Activity of the Ethanolic Extract from Uncaria lanosa Wallich var. appendiculata Ridsd in the Forced Swimming Test and in the Tail Suspension Test in Mice.

This study investigated the antidepressant activity of ethanolic extract of U. lanosa Wallich var. appendiculata Ridsd (UL(EtOH)) for two-weeks administrations by using FST and TST on mice. In order to understand the probable mechanism of antidepressant-like activity of UL(EtOH) in FST and TST, the researchers measured the levels of monoamines and monoamine oxidase activities in mice brain, and combined the antidepressant drugs (fluoxetine, imipramine, maprotiline, clorgyline, bupropion and ketanserin). Lastly, the researchers analyzed the content of RHY in the UL(EtOH). The results showed that UL(EtOH) exhibited antidepressant-like activity in FST and TST in mice. UL(EtOH) increased the levels of 5-HT and 5-HIAA in cortex, striatum, hippocampus, and hypothalamus, the levels of NE and MHPG in cortex and hippocampus, the level of NE in striatum, and the level of DOPAC in striatum. Two-week injection of IMI, CLO, FLU and KET enhanced the antidepressant-like activity of UL(EtOH). UL(EtOH) inhibited the activity of MAO-A. The amount of RHY in UL(EtOH) was 17.12 mg/g extract. Our findings support the view that UL(EtOH) exerts antidepressant-like activity. The antidepressant-like mechanism of UL(EtOH) may be related to the increase in monoamines levels in the hippocampus, cortex, striatum, and hypothalamus of mice.

Antiosteoporotic activity of Davallia formosana.

ETHNOPHARMACOLOGICAL RELEVANCE: [corrected] In Taiwanese folk medicine, Davallia formosana is used to treat bone diseases, including osteoporosis. AIM: This study evaluated the anti-osteoporotic effect of ethanolic extract derived from Davallia formosana (DFE). MATERIALS AND METHODS: In this in vitro study, we investigated the inhibitory action of DFE on RANKL-stimulated osteoclastogenesis. The in vivo effects of DFE on bone metabolism were evaluated using ovariectomized (OVX) rats orally administered DFE (200, 500 mg/kg), alendronate (2.5 mg/kg, three times a week) or its vehicle for 12 weeks. RESULTS: This in vitro study demonstrated that DFE inhibited osteoclast differentiation, and also isolated the active component, (-)-epicatechin 3-O-ß-D-allopyranoside (ECAP). DFE did not affect the body or vaginal weight in OVX rats. The bone mineral density and bone calcium content in OVX rats were lower in the control group showing that DFE was able to prevent significant bone loss. In addition, the three point bending test and the microcomputer tomography scanning showed that DFE treatment enhanced bone strength and inhibited the deterioration of trabecular microarchitecture. In the biochemical assay, DFE decreased urinary deoxypyridinoline and calcium concentrations, but did not inhibit serum alkaline phosphatase activities, indicating that it ameliorated bone loss via inhibition of bone reabsorption. CONCLUSIONS: These results suggest that DFE may represent a useful remedy for the treatment of bone reabsorption diseases such as osteoporosis. In addition, ECAP could be used as a marker compound to control the quality of DFE.

Annonacin induces cell cycle-dependent growth arrest and apoptosis in estrogen receptor-α-related pathways in MCF-7 cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Tamoxifen resistance is common in estrogen receptor-α (ERα)-positive breast cancers. Pawpaw and soursop are anticancer annonaceous plants in complementary medicine. Thus, we studied the effects of annonacin, an annonaceous acetogenin, in breast cancer cells. MATERIALS AND METHODS: Cell growth and ERα-related pathways were studied. The effects of annonacin were tested in MCF-7 xenografts in nude mice. RESULTS: In ERα-positive MCF-7 cells, annonacin (half-effective dose ED(50) = 0.31 µM) and 4-hydroxytamoxifen (ED(50) = 1.13 µM) decreased cell survival whereas annonacin (0.5-1 µM) increased cell death at 48 h. Annonacin and 4-hydroxytamoxifen were additive in inhibiting cell survival. Annonacin (0.1 µM) induced G(0)/G(1) growth arrest while increasing p21(WAF1) and p27(kip1) and decreasing cyclin D1 protein expression. Annonacin (0.1µM) decreased cyclin D1 protein expression more than 4-hydroxytamoxifen (1 µM). Annonacin (0.1 µM) increased apoptosis while decreasing Bcl-2 protein expression. The combination of annonacin (0.1 µM) and 4-hydroxytamoxifen (1 µM) decreased Bcl-2 protein expression and ERα transcriptional activity more than annonacin (0.1 µM) did alone. Annonacin, but not 4-hydroxytamoxifen, decreased ERα protein expression. Moreover, annonacin decreased phosphorylation of ERK1/2, JNK and STAT3. In nude mice, annonacin decreased MCF-7 xenograft tumor size at 7-22 days. Moreover, annonacin decreased ERα, cyclin D1 and Bcl-2 protein expression in the xenograft at 22 days. CONCLUSIONS: Annonacin induced growth arrest and apoptosis in ERα-related pathways in MCF-7 cells. Annonacin and 4-hydroxytamoxifen were additive in inhibiting cell survival and ERα transcriptional activity. Moreover, annonacin attenuated MCF-7 xenograft tumor growth while inhibiting ERα, cyclin D1 and Bcl-2 protein expressions in nude mice.

Data feedback reduces door-to-balloon time in patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention.

Current guidelines recommend a goal of door-to-balloon (D2B) time < 90 min for patients undergoing primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI). We aim to prospectively determine the effect of data feedback on D2B time and its seven individual components in primary PCI. From December 7, 2007, to June 2, 2009, 116 consecutive patients with STEMI who received PCI within 12 h of symptom onset were enrolled, including 56 patients before and 60 patients after the implementation of data feedback on July 28, 2008. The proportion of patients treated within 90 min increased from 26.8 to 55.0% (p = 0.002). On multivariable analyses, data feedback (OR 5.3, p = 0.003), known coronary artery disease (OR 5.6, p = 0.043), regular hours presentation (OR 3.3, p = 0.048), and arrival by transfer (OR 14.0, p = 0.003) were independent predictors of a D2B time less than 90 min. Median D2B time decreased from 112 min before data feedback to 87 min after data feedback (p < 0.001). The most significant decrease occurred in median door-to-ECG (11 vs. 3 min, p < 0.001), consult-to-cardiologist (5 vs. 3 min, p < 0.001), and puncture-to-balloon (21 vs. 17 min, p = 0.004) time. Data feedback to the emergency department and catheterization laboratory staff decreases D2B time in primary PCI. This simple approach may be the best first step to decrease D2B time in hospitals that are still striving to achieve the goal of D2B time < 90 min.

Analgesic and anti-inflammatory activities of the aqueous extracts from three Flemingia species.

I-Tiao-Gung has long been used in the Kinmen area of Taiwan as an anti-inflammatory agent for the treatment of rheumatic illness. The roots of Flemingia lineata (FL), Flemingia macrophylla (FM) and Flemingia prostrata (FP) are also used as I-Tiao-Gung in the Taiwan markets. In the present study, we investigated the analgesic effect of aqueous extracts of Flemingia lineata (FL), Flemingia macrophylla (FM), and Flemingia prostrata (FP) by acetic acid-induced writhing response, formalin test, and the anti-inflammatory effect of FM, FL and FP by lambda-carrageenan-induced paw edema in mice. We also detected the changes in the activities of superoxide dismutase (SOD), glutathione reductase (GRx) and glutathione peroxidase (GPx) of liver in the lambda-carrageenan-induced paw edema in mice to investigate the anti-inflammatory mechanism of FL and FM. The results showed that FL and FM significantly inhibited the acetic acid-induced writhing response and formalin-induced licking time during the late phase (p < 0.001). FL and FM also significantly decreased the lambda-carrageenan-induced paw edema (p < 0.001). FL and FM significantly increased the GRx and GPx activities in the liver and decreased the levels of malondialdehyde (MDA) and nitric oxide (NO) in the edema paw (p < 0.001). These results indicated that FL and FM possessed analgesic and anti-inflammatory effects. The anti-inflammatory mechanism of FL and FM might be related to the decrease in the level of MDA in the edema paw via increasing the activities of GPx and GRx in the liver and decreasing the NO level in the edema paw.

Grifola frondosa (maitake mushroom) water extract inhibits vascular endothelial growth factor-induced angiogenesis through inhibition of reactive oxygen species and extracellular signal-regulated kinase phosphorylation.

Grifola frondosa, a large edible mushroom also known as maitake, has been used as a health food for centuries in China and Japan. In the present study, we examined anti-angiogenic activity of a water extract of the fruiting body of G. frondosa (GFW). An in vivo angiogenesis assay using chick chorioallantoic membrane revealed that GFW (1-100 microg/mL) dose-dependently inhibited vascular endothelial growth factor (VEGF)-induced angiogenesis. In addition, GFW inhibited VEGF-induced proliferation, chemotactic migration, and capillary-like tube formation of human umbilical vein endothelial cells (HUVECs) in a concentration-dependent manner. Upon stimulation by VEGF, HUVECs rapidly increased reactive oxygen species production, which was significantly blocked by the treatment with GFW. Moreover, phosphorylation of extracellular signal-regulated kinase 1/2, a downstream signaling molecule following VEGF receptor activation, was also inhibited by GFW. The results indicate that GFW effectively inhibit angiogenesis by blocking VEGF signaling and suggest that G. frondosa fruiting body may be a valuable medicinal food for treatment of angiogenesis-associated human diseases.

Release of acetylcholine by syringin, an active principle of Eleutherococcus senticosus, to raise insulin secretion in Wistar rats.

The present study is designed to screen the effect of syringin, an active principle purified from the rhizome and root parts of Eleutherococcus senticosus (Araliaceae), on the plasma glucose and investigate the possible mechanisms. Plasma glucose decreased in a dose-dependent manner 60 min after intravenous injection of syringin into fasting Wistar rats. In parallel to the decrease of plasma glucose, increases of plasma insulin level as well as the plasma C-peptide was also observed in rats receiving same treatment. Both the plasma glucose lowering action and the raised plasma levels of insulin and C-peptide induced by syringin were also inhibited by 4-diphenylacetoxy-N-methylpiperdine methiodide (4-DAMP), the antagonist of the muscarinic M3 receptors, but not affected by the ganglionic nicotinic antagonist, pentolinium or hexamethonium. Moreover, disruption of synaptic available acetylcholine (ACh) using an inhibitor of choline uptake, hemicholinium-3, or vesicular acetylcholine transport, vesamicol, abolished these actions of syringin. Also, physostigmine at concentration sufficient to inhibit acetylcholinesterase enhanced the actions of syringin. Mediation of ACh release from the nerve terminals to enhance insulin secretion by syringin can thus be considered. The results suggest that syringin has an ability to raise the release of ACh from nerve terminals, which in turn to stimulate muscarinic M3 receptors in pancreatic cells and augment the insulin release to result in plasma glucose lowering action.